@article {pmid40601184, year = {2025}, author = {Rico-Caballero, V and Romero-Rivera, M and Moreno-Blanco, A and Aira, A and Casals-Pascual, C and Rodríguez-Jiménez, C and Quereda, C and Soriano, A and Del Campo, R}, title = {Fecal microbiota transplant as treatment for recurrent urinary tract infections: a proof-of-concept study.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, pmid = {40601184}, issn = {1435-4373}, }
@article {pmid40600295, year = {2025}, author = {Shao, H and Min, F and Bai, T and Liu, Y and Zheng, S and Wu, Y and Di, C and Lin, M and Li, X and Chen, H}, title = {Bifidobacterium breve M-16V alleviates cow's milk allergy by regulating the gut microbiota and metabolites in human microbiota-associated mice.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo02012c}, pmid = {40600295}, issn = {2042-650X}, abstract = {Cow's milk allergy (CMA) is one of the most common food allergies, especially in infants and young children. Growing evidence from animal studies has shown that some specific probiotics can alleviate CMA, but clinical evidence remains insufficient due to certain limitations. In the present study, we transplanted fecal material from three CMA children into antibiotic-pretreated mice (hum-CMA mice) to mimic the intestinal microecology of allergic individuals, followed by allergen sensitization and Bifidobacterium breve (B. breve) M-16V intervention. Our results showed that B. breve M-16V effectively ameliorated CMA symptoms and allergy-related indicators in hum-CMA mice. Moreover, B. breve M-16V differentially affected the composition of intestinal microbes, but the abundance of beneficial bacteria, such as short-chain fatty acid-producing bacteria, was consistently elevated in all three groups of hum-CMA mice. Subsequent untargeted metabolomics analyses revealed that B. breve M-16V improved the pattern of serum metabolites, and these differential metabolites were mainly involved in glutathione metabolism, glycerophospholipid metabolism, and tryptophan metabolism. All the findings indicate that B. breve M-16V can alleviate the anaphylactic reaction in hum-CMA mice by regulating the intestinal microbiota and metabolites, providing a valuable scientific basis for the clinical application of probiotics in food allergy.}, }
@article {pmid40600174, year = {2025}, author = {Ebrahimi, R and Shahrokhi Nejad, S and Fekri, M and Nejadghaderi, SA}, title = {Advancing prostate cancer treatment: the role of fecal microbiota transplantation as an adjuvant therapy.}, journal = {Current research in microbial sciences}, volume = {9}, number = {}, pages = {100420}, pmid = {40600174}, issn = {2666-5174}, abstract = {Prostate cancer (PCa) is a major cause of cancer-related deaths worldwide. While current treatments such as surveillance, surgery, and radiation are effective, they have their limitations. These can include patient incompliance due to side effects or resistance to hormonal changes, highlighting the need for alternative approaches. Human microbiota, a complex and dynamic host, plays a significant role in the homeostasis and is associated with several diseases or cancers in cases of dysregulation and dysbiosis. Research on fecal microbiota profiling and its association with certain cancers has opened new possibilities for preventing and managing tumor progression. One such possibility is fecal microbial transplantation (FMT). Studies show that different composition of urinary microbiota is found in various urinary tract diseases. Gut microbiota can regulate immune response against tumors; therefore, FMT may help modulate gut microbiota in a way that potentially enhances responses to immune checkpoint inhibitors, as suggested by emerging evidence in other cancers, though this needs further validation in PCa. Nevertheless, long-term complications and the safety of FMT are still questioned. We reviewed the roles of gut microbiota in PCa and suggested FMT as a potential tool in the treatment of PCa, which needs further investigations.}, }
@article {pmid40599506, year = {2025}, author = {Alnahwi, HH and AlGhawi, RJ and Alsahaf, HAA and Ahmed, E}, title = {Recurrent Clostridioides difficile Infection (CDI) in Patients Treated With Vancomycin at Johns Hopkins Aramco Healthcare (JHAH), Dhahran, Saudi Arabia.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e85116}, pmid = {40599506}, issn = {2168-8184}, abstract = {Introduction Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea with a significant risk of recurrence, posing challenges for patient management and infection control. Identifying risk factors for recurrence is essential to improve outcomes and prevent relapses. Methods This retrospective cohort study included 860 adult patients (≥18 years) treated with vancomycin for CDI at Johns Hopkins Aramco Healthcare (JHAH) in Dhahran, Saudi Arabia, between January 2015 and December 2020. Patients with confirmed CDI based on stool polymerase chain reaction (PCR) or toxin assays, complete medical records, and adequate follow-up data were included. The study excluded those not treated with vancomycin, under 18 years of age, with incomplete records, those who received fecal microbiota transplantation or experimental treatments, and those lacking follow-up data. Data on demographics, comorbidities, hospitalization, medication use, and recurrence were analyzed using univariate and multivariate logistic regression models. Results Univariate analysis showed that age 40-65 years (OR = 1.53; 95% CI: 1.024-2.285; p = 0.038), age >65 years (OR = 1.894; 95% CI: 1.282-2.799; p = 0.001), cirrhosis (OR = 9.104; 95% CI: 1.233-67.192; p = 0.03), hospitalization (OR = 1.974; 95% CI: 1.417-2.749; p < 0.0001), and type 2 diabetes mellitus (OR = 1.65; 95% CI: 1.106-2.462; p = 0.014) were significantly associated with CDI recurrence. After adjusting for confounders, only hospitalization remained a statistically significant independent predictor (OR = 1.597; 95% CI: 1.098-2.325; p = 0.014). Conclusion Hospitalization was identified as the most significant independent risk factor for CDI recurrence. These findings highlight the need for enhanced infection control practices and close monitoring of hospitalized patients with CDI. Future prospective and multicenter studies are recommended to validate these results and explore additional modifiable risk factors to reduce recurrence rates.}, }
@article {pmid40599494, year = {2025}, author = {Boton, N and Patel, PK and Beekmann, SE and Polgreen, PM and Buckel, WR and Mahoney, MV and Mehrotra, P and Lee, MSL}, title = {Clinician Management Preferences for Clostridioides difficile Infection in Adults: A 2024 Emerging Infections Network Survey.}, journal = {Open forum infectious diseases}, volume = {12}, number = {7}, pages = {ofaf335}, pmid = {40599494}, issn = {2328-8957}, abstract = {BACKGROUND: The 2021 Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) guidelines for Clostridioides difficile infection (CDI) introduced new recommendations for managing initial and recurrent CDI. Since then, new microbiome-based therapies for preventing recurrent CDI have become available. We surveyed infectious diseases (ID) clinicians to understand their experiences, practices, and challenges in CDI management.<br><br>METHODS: An electronic survey was distributed to members of the IDSA Emerging Infections Network in May 2024, targeting ID physicians and healthcare professionals in the United States who manage adult CDI. The survey assessed treatment preferences, clinical practices, and barriers to accessing and prescribing CDI therapies.<br><br>RESULTS: Of the 500 respondents who reported treating CDI in the past year, 83% (417/500) indicated that vancomycin was their most frequently prescribed agent for initial, nonfulminant CDI. Additionally, 72% (357/498) reported that their institutional guidelines recommended vancomycin as the first-line agent. The most common barrier to fidaxomicin use was challenges with outpatient insurance coverage (82% [408/496]). Bezlotoxumab was available to 74% (370/500) of respondents, though 33% (165/497) indicated they do not use bezlotoxumab routinely. Most clinicians (87% [437/500]) had previously recommended fecal microbiota transplantation (FMT) for recurrent CDI, though only 48% (239/500) had current access to FMT using donor stool. Fecal microbiota live-jslm was available to 36% (179/500), and fecal microbiota spores live-brpk was available to 30% (150/500).<br><br>CONCLUSIONS: Significant barriers, including high costs, insurance challenges, and limited availability of CDI therapies, impact clinical decision-making and adherence to guideline recommendations.}, }
@article {pmid40597484, year = {2025}, author = {Zhang, C and Zhang, X and Qiu, H and Song, Q and Wang, Y and Zhang, C and Zhang, Q}, title = {Fermented Gastrodia elata Bl. Intervenes gut microbiota and amino acid metabolism in zebrafish to promote 5-HT homeostasis against sleep disturbances.}, journal = {Food research international (Ottawa, Ont.)}, volume = {217}, number = {}, pages = {116757}, doi = {10.1016/j.foodres.2025.116757}, pmid = {40597484}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Zebrafish ; *Amino Acids/metabolism ; *Serotonin/metabolism ; *Gastrodia/chemistry ; Homeostasis/drug effects ; *Fermented Foods ; Fermentation ; *Sleep Wake Disorders/prevention &amp; control ; Sleep Initiation and Maintenance Disorders/chemically induced ; Fecal Microbiota Transplantation ; }, abstract = {Sleep disturbances (SD) is a prevalent health issue in modern society. Consequences involve negative impacts on numerous aspects of physical, psychological, and daily life. This study aimed to elucidate the protective effects of Fermented Gastrodia elata Bl. (FGE) against pentylenetetrazole (PTZ)-induced SD and uncover the underlying molecular mechanisms. Our findings revealed that FGE significantly attenuated PTZ-induced insomnia behavior, circadian rhythm disturbances, and compromised gut barrier functions. Mechanistically, gut microbiota and 5-HT within the microbiota-gut-brain axis are the key regulators in short-term SD. Fecal microbiota transplantation (FMT) experiment identified gut microbiota as a key mediator and potential therapeutic target for FGE. The comprehensive analysis of 16S rRNA sequencing and metabolomic analysis showed that amino acid metabolism-related pathways as key factors of FGE intervention. Notably, omics joint analysis demonstrated a strong association between the variations of the intestinal microbiota among different groups and the notable alterations in the brain metabolomic landscape. Meanwhile, the remodeling of intestinal microbial structure and metabolites drove the homeostasis of 5-HT levels in different tissues. Importantly, exogenous keystone bacteria supplementation to sleep-deprived zebrafish restored insomnia responses and amino acid metabolism. Targeted amino acid metabolism further confirmed amino acid metabolism as the central mechanistic pathway through which FGE exerts its protective function. Collectively, Collectively, these findings suggested that FGE showed a significant preventative action on short-term SD by intervening gut microbiota and amino acid metabolism in zebrafish to promote 5-HT homeostasis, which offers perspectives into new preventive strategies of traditional Chinese medicine dietary supplements for transient insomnia.}, }
@article {pmid40596796, year = {2025}, author = {Liu, K and Wang, Y and Zhou, J and van der Meij, JJ and van der Laan, LJW and Li, P and Pan, Q}, title = {Decoding the role of the intestinal epithelium in hepatitis E virus infection using a human organoid prototype of "gut-liver" axis.}, journal = {Virology}, volume = {610}, number = {}, pages = {110615}, doi = {10.1016/j.virol.2025.110615}, pmid = {40596796}, issn = {1096-0341}, abstract = {Hepatitis E virus (HEV), a leading cause of acute viral hepatitis worldwide, is primarily transmitted via the fecal-oral route. A clinical study has reported that the intestine of a chronic hepatitis E patient is positive for HEV. However, whether the intestinal epithelium acts as a barrier for HEV transmission or whether productive enteric infection enhances transfer of the virus to the liver remains unclear. The advent of organoid technology provides a valuable platform for advancing the study of HEV-host interactions in a more physiologically relevant context. In this study, we demonstrate that primary human intestinal organoids (HIOs) efficiently support HEV replication. The infection was sustained in differentiated HIOs with specific phenotypes of intestinal cell types, namely enterocyte, goblet cell, and enteroendocrine cell lineages. Next, we constructed a gut-liver axis model using a transwell system by co-culturing HIOs with human liver-derived organoids. Importantly, infectious viral particles produced in HIOs were capable of transmission to human liver-derived organoids in this model. Bile acids are essential mediators of gut-liver crosstalk. We found that supplementing human bile or the primary bile acid chenodeoxycholic acid inhibited HEV replication in organoids via the farnesoid X receptor (FXR) signaling pathway. The effects of the secondary bile acid, ursodeoxycholic acid, were opposite and promoted viral replication. In conclusion, this model provides a novel approach to study the gut-liver axis in HEV transmission and the impact of bile acids in modulating HEV infection.}, }
@article {pmid40596758, year = {2025}, author = {Wang, J and Tan, H and Ye, Z and Weng, S and Shi, Y and Xu, J and Liu, H and Li, J and Huang, L and Zhai, L and Luo, H and Lin, Z and Zhong, C and Tang, J and Wang, Z and Zhang, H and Zhang, B and Huang, C}, title = {Gut microbial Nordihydroguaiaretic acid suppresses macrophage pyroptosis to regulate epithelial homeostasis and inflammation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2518338}, doi = {10.1080/19490976.2025.2518338}, pmid = {40596758}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; Fecal Microbiota Transplantation ; *Colitis/microbiology/chemically induced ; Homeostasis/drug effects ; *Macrophages/drug effects ; *Masoprocol/pharmacology/metabolism ; *Pyroptosis/drug effects ; Mice, Inbred C57BL ; Dysbiosis/microbiology ; Male ; Dextran Sulfate ; Disease Models, Animal ; Intestinal Mucosa/drug effects ; Aging ; Inflammatory Bowel Diseases/microbiology ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Humans ; }, abstract = {BACKGROUND: Aging is associated with increased severity of inflammatory bowel disease (IBD). Gut senescence and altered environmental factors contribute to changes in the intestinal metabolome, particularly in frail older individuals. However, the role of age-associated dysbiosis, characterized by a decline in beneficial gut microbiota and their metabolites, in exacerbating IBD remains unclear.<br><br>METHODS: To investigate the impact of aging-associated dysbiosis on colitis development, we employed fecal microbiota transplantation (FMT) in wild-type and IL-10-deficient mice. Aged mice were treated with gut microbiota from either young or aged mice and then subjected to dextran sulfate sodium (DSS) to induce experimental colitis. 16S rDNA sequencing and metabolomics were used to analyze microbial and metabolite profiles. Single-cell RNA sequencing (scRNA-seq) was performed to characterize lamina propria CD45[+] immune cell composition.<br><br>RESULTS: Aged mice receiving microbiota from young mice exhibited less severe colitis than those receiving microbiota from aged mice, as evidenced by reduced disease activity, weight loss, and colonic shortening. Besides, aged mice displayed a significant decrease in the Lactobacillus population, accompanied by a reduction in Nordihydroguaiaretic acid (NDGA) levels. Decreased fecal NDGA levels were also observed in both IBD patients and elderly individuals. Administration of NDGA alleviated experimental colitis by downregulating the GSDMD/NR4A1/NLRP3 axis-mediated macrophage pyroptosis. Deletion of GSDMD in macrophages significantly diminished the protective effect of NDGA on colitis.<br><br>CONCLUSIONS: Our findings demonstrate that aging is associated with dysbiosis and reduced NDGA production, which increases susceptibility to intestinal inflammation. Gut microbial NDGA exhibits potential anti-inflammatory activity in colitis, suggesting a promising therapeutic target for aged-related IBD.}, }
@article {pmid40593111, year = {2025}, author = {Zhou, X and Wei, C and Liu, J and Xia, X and Wang, L and Li, X}, title = {Cold environment regulates ischemic stroke through modulation of gut microbiota.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {21558}, pmid = {40593111}, issn = {2045-2322}, support = {42275197//National Natural Science Foundation of China/ ; TJYXZDXK-065B//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; TJWJ2023XK007//the Key Projects of Tianjin Municipal Health Commission/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Cold Temperature/adverse effects ; Animals ; Fecal Microbiota Transplantation ; Mice ; Male ; Mice, Inbred C57BL ; Humans ; Dysbiosis/microbiology ; *Ischemic Stroke/microbiology/etiology ; Female ; Middle Aged ; Platelet Aggregation ; Aged ; Methylamines ; }, abstract = {Many diseases are influenced by environmental temperature, and recent studies have confirmed that cold exposure increases the risk of conditions such as ischemic stroke (IS). However, direct evidence supporting this hypothesis is lacking, and the molecular mechanisms through which cold exposure affects IS remain unclear. In this study, we found that chronic cold exposure increased platelet aggregation and the levels of certain inflammatory factors in high-risk stroke patients (HR), thereby increasing the risk of IS. Furthermore, before and after a cold wave, we observed gut microbiota dysbiosis in the HR group, including reduced relative abundance differences in Lachnospiraceae and Ruminococcaceae. The relative abundances of the Prevotella_9 and Catenibacterium genera increased, whereas that of Anaerostipes decreased. Notably, the results of fecal microbiota transplantation (FMT) indicated that cold-adapted microbiota transplantation partially replicated the microbiota characteristics of each donor subject and replicated the effects of cold exposure in C57BL/6J mice. Cold exposure impaired intestinal barrier function and interfered with microbial functions, such as increased lipid metabolism and LPS production, particularly by increasing the levels of TMAO derived from the gut microbiota. Our findings identify the significant role of abnormal gut microbiota-derived metabolites in cold exposure-related IS and highlight the potential opportunity to prevent or treat cold-related IS through the modulation of the gut microbiota.}, }
@article {pmid40593020, year = {2025}, author = {Yue, Y and Yao, B and Liao, F and He, Z and Sangsawad, P and Yang, S}, title = {Fecal microbiota transplantation improves Sansui duck growth performance by balancing the cecal microbiome.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {22403}, pmid = {40593020}, issn = {2045-2322}, support = {31960682//The National Nature Science Foundation of China/ ; 31960682//The National Nature Science Foundation of China/ ; 31960682//The National Nature Science Foundation of China/ ; 31960682//The National Nature Science Foundation of China/ ; 31960682//The National Nature Science Foundation of China/ ; }, abstract = {Improving growth performance is vital in poultry production. Although several studies have established associations between gut microbiota and growth, the direct impacts remain unclear. A total of 120 1-day-old Sansui ducks were randomly assigned to the FMT and CON groups. From the 1st day, ducks in the FMT group were orally administrated with 0.5 mL fecal microbiota suspension for three consecutive days, while sterile PBS solution was used as a substitute in the CON group. The results revealed that FMT improved average daily gain (ADG) (P < 0.001) and body weight (BW) (P < 0.001), with a tendency for a better feed conversion rate (FCR) (P = 0.062). LEfSe analysis indicated a significant increase in the abundance of the Lactobacillus (P < 0.001), Bifidobacterium (P = 0.006), Megamonas (P = 0.008), and Subdoligranulum (P = 0.005) in the FMT group. Similarly, the phyla Firmicutes/Bacteroidetes ratio was higher in the FMT group compared to the CON group. Additionally, the ACE, Chao, and Shannon indices were also significantly higher in the FMT group (P < 0.001). To sum up, FMT enhanced growth performance, which could be associated with reducing proinflammatory pathogen colonization in the duck cecum. This modulating effect likely results from increased microbial diversity and the enrichment of beneficial bacteria.}, }
@article {pmid40592776, year = {2025}, author = {Zhang, X and Ishikawa, D and Nagahara, A}, title = {Fecal Microbiota Transplantation for Immune Regulation: Improving Ulcerative Colitis and Enhancing Cancer Immunotherapy.}, journal = {International immunology}, volume = {}, number = {}, pages = {}, doi = {10.1093/intimm/dxaf038}, pmid = {40592776}, issn = {1460-2377}, abstract = {The gut microbiota plays an integral role in maintaining health and regulating various host functions, including immune responses. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach to restore gut microbial balance. Although widely recognized for its efficacy in treating ulcerative colitis (UC), FMT is now being investigated as an adjuvant therapy to enhance the efficacy of immune checkpoint inhibitors (ICIs) in cancer treatment. This review summarizes the clinical applications of FMT in UC treatment and its potential role in cancer immunotherapy. FMT exhibits varying degrees of efficacy in the treatment of UC, with differences in outcomes attributed to variations in administration methods and donor selection. In cancer therapy, FMT has demonstrated the potential to improve ICI responses, particularly in patients with melanoma. However, its effects on other cancers remain unclear. Although FMT holds promise for UC and cancer immunotherapy, challenges such as inconsistent clinical outcomes and methodological variations persist. Standardized protocols and mechanistic studies are crucial to optimize FMT-based therapeutic strategies, and further research is required to establish its efficacy under diverse clinical conditions.}, }
@article {pmid40592615, year = {2025}, author = {Sasaki, K and Takeshima, Y and Fujino, A}, title = {Reproducing in vitro artificial gut microbiota using glycerol stocks of fecal cultures combined with different prebiotic additives.}, journal = {Journal of bioscience and bioengineering}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jbiosc.2025.06.002}, pmid = {40592615}, issn = {1347-4421}, abstract = {Artificial human microbiota can be produced in gut simulators from cryopreserved stocks. They are used for in vitro fermentation models and as alternative material for fecal microbiota transplantation therapy. However, current methods have limited information on microbial structure at the genus level and present challenges during cryopreservation. In this study, we used an edible glycerol stock of fecal batch culture instead of fresh feces to create artificial gut microbiota. Three glycerol stocks, generated through in vitro fecal fermentation with different prebiotic additives (such as fructooligosaccharide, xylan, pectin, and guar gum), were combined. Profiling via 16S rRNA gene amplicon sequencing revealed that the artificial gut microbiota derived from the combined glycerol stocks showed more amplicon sequence variants than those from a single glycerol stock. In the artificial microbiota, relative abundance values of common genera such as Bifidobacterium, Bacteroides, Prevotella, Faecalibacterium, and Escherichia were more than 10 % of those found in the original feces. Other commensal genera such as Collinsella, Anaerobutyricum hallii (formerly Eubacterium hallii) group, Anaerostipes, Blautia, Dorea, Lachnospiraceae UCG-004, and Oscillospiraceae UCG-003 were similarly maintained. Our data indicated that combining glycerol stocks of fecal cultures with different additives in a batch-type gut simulator is a useful option for producing artificial gut microbiota, the taxonomic compositions of which are comparable to those of the original feces.}, }
@article {pmid40592538, year = {2025}, author = {Cymbal, M and Chatterjee, A and Baggott, B}, title = {Fecal microbiota transplantation: Current evidence and future directions.}, journal = {Cleveland Clinic journal of medicine}, volume = {92}, number = {7}, pages = {421-428}, doi = {10.3949/ccjm.92a.24107}, pmid = {40592538}, issn = {1939-2869}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/trends ; *Clostridium Infections/therapy ; *Gastrointestinal Microbiome ; Clostridioides difficile ; Dysbiosis/therapy ; }, abstract = {As we advance our understanding of the gut microbiota, the implications of dysbiosis are becoming increasingly apparent. Fecal microbiota transplantation (FMT), a well-established procedure, is recognized for effectively treating recurrent Clostridioides difficile infection, prompting further investigation into its other possible clinical applications. Donor selection and screening are essential to ensure safety and efficacy. Product development and standardization, such as the US Food and Drug Administration-approved live biotherapeutic products Rebyota and Vowst, are helping efforts to evaluate FMT for other gastrointestinal and extraintestinal diseases. However, additional clinical trials are needed to support its use beyond recurrent C difficile infection.}, }
@article {pmid40591032, year = {2025}, author = {Abebaw, D and Akelew, Y and Adugna, A and Tegegne, BA and Teffera, ZH and Belayneh, M and Fenta, A and Selabat, B and Kindie, Y and Baylie, T and Mekuriaw, MG and Jemal, M and Atnaf, A}, title = {Immunomodulatory properties of the gut microbiome: diagnostic and therapeutic potential for rheumatoid arthritis.}, journal = {Clinical and experimental medicine}, volume = {25}, number = {1}, pages = {226}, pmid = {40591032}, issn = {1591-9528}, mesh = {Humans ; *Arthritis, Rheumatoid/therapy/diagnosis/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/immunology ; Probiotics/therapeutic use ; *Immunomodulation ; Fecal Microbiota Transplantation ; Biomarkers ; Animals ; }, abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent joint inflammation, synovial hyperplasia, and progressive joint destruction. Despite advancements in biologic disease-modifying antirheumatic drugs (bDMARDs) and TNF-α blockers, many RA patients still require more effective treatment options. Although genetic and environmental factors play a role in RA development, recent studies have emphasized the influence of the gut microbiota on disease onset and progression. Dysbiosis, or an imbalance in the gut microbial composition, has been linked to immune dysregulation, increased intestinal permeability, and systemic inflammation, all contributing to RA development. Research has revealed changes in the gut microbiome of RA patients, including an increased prevalence of Prevotella copri and a decreased presence of beneficial microbes such as Bifidobacterium, Bacteroides, and Lactobacillus. RA patients exhibit altered metabolite profiles, with reduced levels of short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, which are linked to immune regulation and intestinal barrier function. Specific metabolites, such as L-arginine, phosphorylcholine, and arachidonic acid, have potential as RA biomarkers, with predictive value for diagnosis. Therapeutic approaches focusing on the microbiome, including probiotics, fecal microbiota transplantation, and traditional medicines, show promise in alleviating RA symptoms and regulating immune function. This review provides an updated overview of the immunomodulatory effects of the gut microbiome and explores its potential applications in the diagnosis and treatment of RA.}, }
@article {pmid40589476, year = {2025}, author = {Olajide, TS and Ijomone, OM}, title = {Targeting gut microbiota as a therapeutic approach for neurodegenerative diseases.}, journal = {Neuroprotection}, volume = {3}, number = {2}, pages = {120-130}, pmid = {40589476}, issn = {2770-730X}, abstract = {Recent evidence suggests a more important role of the gut microbiota in neurodegenerative diseases (NDDs) given its relationship through the microbiota-gut-brain as an active communication system aiding in maintaining homeostasis between the brain and the gut. This review focuses on how modulation of gut microbiota can serves as a therapeutic strategy for NDDs, emphasizing the neuroprotective effects of probiotics. Probiotics are live microorganisms that confer health benefits, and their interaction with gut-microbiota influences neurogenesis, neurotransmitter regulation, and neuroinflammation. Recent advancements, including germ-free animal models, fecal microbiota transplantation (FMT), and diverse probiotic strains, have revealed the underlying mechanisms linking gut health to brain function. Notably, several Lactobacillus and Bifidobacterium species have been shown to exert neuroprotective effects via the upregulation of neurotrophic factors such as brain-derived neurotrophic factor and enhancing mitochondrial function through reducing the impacts of oxidative stress. Interestingly, FMT has exhibited a degree of success in overcoming cognitive impairment and motor deficits in preclinical studies and clinical trials. However, further research is warranted to explore its therapeutic potential in humans. Overall, this review highlights the significant role of gut microbiota in NDDs and advocates for gut-targeted interventions as innovative approaches to mitigate these diseases.}, }
@article {pmid40589142, year = {2025}, author = {Tiwari, R and Paswan, A and Tiwari, G and Reddy, VJS and Posa, MK}, title = {Perspectives on Fecal Microbiota Transplantation: Uses and Modes of Administration.}, journal = {Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology}, volume = {41}, number = {}, pages = {e20250014}, doi = {10.62958/j.cjap.2025.014}, pmid = {40589142}, issn = {1000-6834}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; Feces/microbiology ; *Nervous System Diseases/therapy ; }, abstract = {Fecal microbiota Transplantation (FMT), often referred to as stool transplantation, fecal transfusion, and fecal bacteria therapy, is considered one of the most medical innovations of the 20th century. Fecal microbiota Transplantation entails filtering and dilution of a healthy donor's feces before injecting it into the recipient's digestive system. In China, it was first administered orally in the fourth century for diarrhea and food poisoning under the name "Yellow Soup." It has recently been widely employed in a variety of clinical settings, including cases of Clostridium difficile infection that are recurring and resistant. By replacing the unhealthy intestinal microbiota with a healthy bacterial community, the FMT treatment aims to enhance the intestinal flora. It also looks at neurological conditions where alterations in gut microbiota are prevalent. We have discussed FMT in the context of its use in conditions affecting the nerve system, such as neurological and other conditions (multiple sclerosis, Parkinson's disease, Alzheimer's disease, stroke, epilepsy, Amyotrophic lateral sclerosis, Tourette syndrome, neuropathic pain, Huntington's diseases, etc.), as well as the role of gut microbiota in many neurological disorders.}, }
@article {pmid40589086, year = {2025}, author = {Yadav, M and Gupta, A and Mathew, B and Tripathi, G and Dalal, N and Sharma, N and Yadav, P and Yadav, G and Singh, R and Bindal, V and Saif, R and Yadav, S and Sharma, N and Pandey, S and Bhat, SH and Singh, R and Kumar, J and Kushwaha, M and Khan, T and Sharma, NK and Bhaskar, A and Dwivedi, VP and Kumar, A and Kumar, N and Tripathi, DM and Trehanpati, N and Anupama Kumara,  and Sharma, S and Sarin, SK and Maras, JS}, title = {Circulating urobilinogen contributes to Inflammation, Intestinal Permeability and corticosteroid non-response in Severe Alcohol-associated Hepatitis.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2025.06.041}, pmid = {40589086}, issn = {1525-0024}, abstract = {Severe alcohol-associated hepatitis (SAH) is a life-threatening condition with high mortality rates and poor response to prednisolone therapy. Identifying reliable early predictors of therapy response and survival is critical. Plasma metabolomics was conducted on 70 SAH patients (50 responders, 20 non-responders) to identify biomarkers for non-response and early mortality. These findings were validated in a cohort of 153 patients and an independent cohort of 245 using high resolution mass spectrometry, machine learning, and severity indices. Temporal metabolic changes indicated interactions between the host and microbiome, with a focus on inflammation and intestinal permeability. Plasma metabolomics revealed that non-responders had significantly higher urobilinogen levels (3.6-fold change). Additionally, a decrease in alpha/beta diversity and temporal metabolic inactivity characterized non-responders. Plasma urobilinogen levels predicted non-response (AUC>0.97) and identified non-survivors (AUC=0.94) with a threshold of >0.07 mg/ml. Urobilinogen levels correlated with bacterial peptides belonging to Firmicutes and Proteobacteria, neutrophil activation, oxidative stress, and pro-inflammatory cytokine production. These changes contributed to non-response by increasing glucocorticoid receptor β expression and compromising intestinal permeability. Fecal microbiota transplantation decreased urobilinogen levels by reducing bilirubin reductase gene-containing microbiota. Plasma urobilinogen >0.07 mg/ml could predict early mortality, and modulation of the gut microbiome may improve outcomes in SAH patients.}, }
@article {pmid40588803, year = {2025}, author = {Hu, J and Feng, T and Zhang, L and Zhou, Q and Zhu, L}, title = {Leveraging gut microbiota for enhanced immune checkpoint blockade in solid tumor therapy.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {40588803}, issn = {2542-5641}, abstract = {Gut microbiota can modulate antitumor immunity and influence immune checkpoint blockade (ICB) therapy efficacy and treatment-associated toxicity. Variations in the therapeutic effect of ICB among individuals are partially attributed to microbiota. This review summarizes current knowledge on how specific bacterial species enhance or hinder ICB outcomes by regulating immune cell activation, antigen presentation, and systemic inflammation. The review further outlines translational strategies to optimize ICB, including microbiota-targeted interventions (e.g., prebiotics, fecal microbiota transplantation, and metabolite therapies) to overcome resistance and mitigate treatment-related toxicities, focusing on immune-related colitis. Additionally, emerging microbial biomarkers in melanoma, lung cancer, and hepatobiliary cancers that predict ICB response are discussed, highlighting the gut microbiome as a potential target for personalized cancer immunotherapy. By integrating mechanistic insights with clinical evidence, this review underscores the potential of microbiota-centered approaches to improve patient outcomes in ICB-based treatments, emphasizing the pivotal role of the gut microbiota in modulating both therapeutic efficacy and immune-related adverse events.}, }
@article {pmid40586386, year = {2025}, author = {Li, K and Arbab, S and Du, Q and Zhou, J and Chen, Y and Tian, Y and Qijie, L and Ullah, H and Zhang, B}, title = {Regulatory and Influencing Factors of Digestive Function in Elderly People: Roles of the Gut Microbiota and Nutritional Interventions.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.0565}, pmid = {40586386}, issn = {2152-5250}, abstract = {Aging is a natural and gradual biological process through which living organisms undergo physical, physiological, and sometimes psychological changes over time. Aging is commonly associated with a decline in gastrointestinal function, leading to various digestive disorders that impact the quality of life of older adults. The gut microbiota is a highly complex ecosystem that plays crucial roles in digestion, metabolic processes, immune functions, and overall health. However, emerging evidence indicates that many elderly individuals maintain relatively stable digestive health, suggesting the influence of modifiable regulatory factors. In this review, we describe the key physiological, microbial, and nutritional factors that regulate and influence digestive function in an aging population. Additionally, we explored the impact of age-associated alterations in the gut microbiota on digestive health challenges in older adults and emphasized the therapeutic potential of targeted nutritional intervention approaches, such as dietary modifications, prebiotics, probiotics, and symbiotic and fecal microbiota transplantation, which have shown promise in rebalancing the gut microbiome and reducing inflammation.}, }
@article {pmid40585700, year = {2025}, author = {Hamza Saeed, M and Qamar, S and Ishtiaq, A and Umaira Khan, Q and Atta, A and Atta, M and Ishtiaq, H and Khan, M and Saeed, MR and Iqbal, A}, title = {Fecal Microbiota Transplantation (FMT) in Clostridium difficile Infection: A Paradigm Shift in Gastrointestinal Microbiome Modulation.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e85054}, pmid = {40585700}, issn = {2168-8184}, abstract = {Clostridium difficile (C. difficile) infection (CDI) poses a tremendous clinical challenge, especially in patients with recurrent disease and antibiotic resistance. Fecal microbiota transplantation (FMT) has become a new therapeutic strategy for restoring gut microbiota and decreasing CDI recurrence. The study aims to assess the clinical effectiveness of FMT in adult subjects with recurrent or refractory CDI, determine its effect on gut microbiome diversity, and track safety outcomes and rates of recurrence post-treatment. FMT was compared against standard antibiotic treatments to establish its efficacy in decreasing infection persistence and improving patients' quality of life. This study examines the efficacy, safety, and modulation of microbiota by FMT in an ensemble of 250 patients diagnosed with CDI, with equal gender distribution and a mean age of 55.61. Among the study participants, 131 (52.4%) underwent FMT by various routes of administration, including 66 (25.2%) through colonoscopy, 73 (29.2%) via a nasogastric tube, 60 (24.0%) via enema, and 54 (21.6%) through oral capsule administration. The success rate for FMT was reported as 88 (35.2%), partial success at 74 (29.6%), and treatment failure at 88 (35.2%). CDI recurrence was reported in 130 (52.0%) of patients after FMT. The gut microbiome enhanced diversity, measured in terms of the Shannon Diversity Index, increased significantly from 3.96 before FMT to 5.88 after FMT, thus indicating a favorable impact on gut microbial composition. Furthermore, 132 (52.8%) converted from C. difficile polymerase chain reaction (PCR) toxin positive to negative, corroborating successful pathogen clearance. On secondary outcomes, the quality of life in patients improved in 90 (36%), antibiotic dependence was reduced in 88 (35.2%), and hospitalization was lessened in 72 (28.8%). Inflammatory markers, such as white blood cell (WBC) counts and C-reactive protein (CRP), went downward but did not reach statistical significance. Logistic regression analysis identified age, severity of CDI, and prior exposure to antibiotics as the main predictors for the efficacy of FMT (p < 0.05). It is concluded that FMT is a promising alternative treatment for recurrent CDI through modulation of gut microbiota and decreasing the severity of infection. Future work is, however, required to establish treatment protocols with optimized results for long-term effectiveness and minimized recurrence risks.}, }
@article {pmid40585508, year = {2025}, author = {Zhu, B and Wu, H and Zhang, H and Song, Q and Xiao, Y and Yu, B}, title = {Gut microbiota from voluntary exercised mice protects the intestinal barrier by inhibiting neutrophil extracellular trap formation.}, journal = {iScience}, volume = {28}, number = {6}, pages = {112763}, pmid = {40585508}, issn = {2589-0042}, abstract = {Ulcerative colitis is an inflammatory bowel disease characterized by impaired intestinal barrier function, dysregulated immune responses, and alterations in the gut microbiota. Excessive formation of neutrophil extracellular traps (NETs), driven by peptidyl arginine deiminase 4 (PAD4) activity, contributes to inflammation modulated by the gut microbiota. In this study, we used a mouse model of dextran sulfate sodium-induced colitis to investigate the effects of voluntary exercise and its underlying mechanisms. Exercise preconditioning attenuated colitis severity, maintained intestinal barrier integrity, normalized gut microbiota composition, and suppressed NET formation. PAD4 inhibition further enhanced these effects. By contrast, the depletion of the gut microbiota by antibiotics largely abolished the benefits of exercise. Additionally, fecal microbiota transplantation from exercised mice recapitulated these protective effects. These findings elucidate the interplay among exercise, gut microbiota, and PAD4-mediated NET formation. Targeting these pathways may offer promising therapeutic strategies for colitis.}, }
@article {pmid40584885, year = {2025}, author = {Guo, M and Gao, H and Wang, Y and Xiang, Y}, title = {Exploring the role of gut microbiota in Parkinson's disease: insights from fecal microbiota transplantation.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1574512}, pmid = {40584885}, issn = {1662-4548}, abstract = {As a common neurodegenerative disease, Parkinson's disease (PD) is typified by α-synuclein (α-syn) aggregation and progressive degeneration of dopaminergic neurons within the substantia nigra. Clinical manifestations encompass motor symptoms and non-motor aspects that severely impair quality of life. Existing treatments mainly address symptoms, with no effective disease-modifying therapies available. The gut microbiota refers to the community of microorganisms that colonize the intestinal tract. The gut microbiota, gut, and brain are all connected via a complicated, mutual communication pathway known as the "gut microbiota-gut-brain axis." Gut microbiota dysbiosis is strongly linked to the onset and course of PD, according to growing data. In individuals with PD, gut dysbiosis correlates with clinical phenotype, disease duration, severity, and progression rates. Mechanistically, gut dysbiosis contributes to PD through enhanced intestinal permeability, increased intestinal inflammation and neuroinflammation, abnormal α-syn aggregation, oxidative stress, and reduced neurotransmitter synthesis. Therefore, focusing on the gut microbiota is regarded as a potentially effective treatment strategy. Fecal microbiota transplantation (FMT) is an emerging approach to modulate gut microbiota, with the goal of recovering microbiota diversity and function by transferring functional intestinal flora from healthy individuals into patients' gastrointestinal tracts. FMT is expected to become a promising therapy of PD and has a broad research and application prospect. Evidence suggests that FMT may restore gut microbiota, ease clinical symptoms, and provide potential neuroprotective benefits. However, the precise therapeutic mechanisms of FMT in PD remain uncertain, necessitating further research to clarify its effectiveness. This review examines alterations in gut microbiota linked to PD, mechanisms through which gut dysbiosis influences the disease, and the latest advancements in FMT research for treating PD, setting the stage for its clinical application.}, }
@article {pmid40583967, year = {2025}, author = {Wang, H and Tian, J and Mi, J}, title = {Clinical effectiveness of fecal microbial transplantation for metabolic syndrome: Advances in clinical efficacy and multi-omics research.}, journal = {Current research in microbial sciences}, volume = {9}, number = {}, pages = {100415}, pmid = {40583967}, issn = {2666-5174}, abstract = {Even though metabolic syndrome (MetS) poses a serious risk to human health and life, existing treatment approaches are not very effective. The impact of gut bacteria on host metabolism has been the subject of numerous research, and fecal microbial transplantation (FMT) has demonstrated great promise in reducing insulin resistance and abdominal obesity in individuals with metabolic syndrome. These FMT investigations have connected alterations in the gut microbiota to clinical indicators of insulin resistance and obesity, in addition to using high-throughput methods to analyze the gut microbiome, metabolome, and epigenome of peripheral blood mononuclear cells in patients with MetS. It is still necessary to clarify and assess the clinical effectiveness and mode of action of FMT in the management of MetS. This review examines the connection between gut bacteria and MetS, the effectiveness of FMT as a treatment, and the changes in the gut microbiome, metabolome, epigenome, and other histones following the intervention. We also discuss the safety of FMT and suggest areas for further investigation.}, }
@article {pmid40582671, year = {2025}, author = {Bi, R and Abbas, W and Li, J and Huang, J and Hu, J and Guo, F and Wang, Z}, title = {Yeast β-glucan ameliorated Salmonella-induced gut impairment in broiler chickens by modulating gut microbiome.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {145630}, doi = {10.1016/j.ijbiomac.2025.145630}, pmid = {40582671}, issn = {1879-0003}, abstract = {Yeast β-glucan (YG) was reported to control Salmonella infection in poultry. Gut microbiota plays an important role in regulating immune functions and intestinal health. However, it is still unclear whether YG protects chickens from Salmonella infection by regulating gut microbiota. The impacts of YG on gut health of chickens infected with Salmonella enteritidis (SE) was investigated through histochemical and immunological methods, along with microbiomics. The role of gut microbiome induced by YG treatment in combating Salmonella infection was explored through FMT. Our findings showed that YG administration significantly ameliorated SE-induced gut impairment by decreasing gut permeability, enhancing intestinal barrier function, inhibiting intestinal inflammation, reducing Salmonella colonization, lowering g_Streptococcus and g_Ligilactobacillus but increasing g_Blautia, g_Bacillus and g_Faecalibacterium relative abundance. Transplantation fecal microbiota from YG-treated healthy donor chickens to antibiotic-treated recipient chicks significantly attenuated gut injury caused by SE infection through decreasing Salmonella colonization and invasion along with intestinal permeability, improving gut morphology, upregulating intestinal tight junction genes and proteins expression, downregulating pro-inflammatory cytokines expression. Additionally, FMT remarkably increased g_Bacteroides and g_Faecalibacterium relative abundances and butyric acid level, decreased g_Ruminococcus-torque-group relative abundance in the cecum.Collectively, we assume that yeast β-glucan alleviated Salmonella-induced gut impairment, a mechanism that is dependent on the gut commensal Bacteroides and Faecalibacterium.}, }
@article {pmid40581627, year = {2025}, author = {Nørgaard, JC and Marandi, RZ and Ilett, EE and Gulay, A and Paredes, R and Lundgren, JD and Jørgensen, M and Sengeløv, H}, title = {The gut microbiome and its resistome as predictors of clinical infections and phenotypic antibiotic resistance in hematopoietic stem cell transplant recipients.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiaf330}, pmid = {40581627}, issn = {1537-6613}, abstract = {A relationship between the gut microbiome composition, its resistome, and risk of clinical infections may exist and was explored here using 663 shotgun-sequenced fecal samples from 276 stem cell transplant patients. E. faecium, E. coli, and E. faecalis were the three most prevalent causes of clinical infection, with vancomycin resistance in E. faecium as the most common antibiotic resistance feature. Associations between the gut microbiome, resistome, and clinical infections were tested, with significant findings (FDR<0.05) evaluated in multivariable analysis. A 10% increase in gut abundance of E. faecium was positively associated with subsequent clinical infection with E. faecium (OR=1.14, p=0.02). Additionally, a 1% increase in vanA gene abundance was positively associated with vancomycin-resistant E. faecium infection (OR=1.27, p<0.01). Here we used metagenomics to enhance the understanding of infectious sources and to identify patients at risk of clinical infection with antibiotic-resistant bacterial strains.}, }
@article {pmid40580532, year = {2025}, author = {Urbonas, T and Petrauskas, D and Kiudelis, V and Jonaitis, L and Skieceviciene, J and Gedgaudas, R and Kiudeliene, E and Valantiene, I and Zykus, R and Varkalaite, G and Inciuraite, R and Trapenske, E and Kulokiene, U and Jonaitis, P and Ramonaite, R and Velickiene, J and Zvirbliene, A and Morkunas, E and Kuliaviene, I and Sumskiene, J and Adamonis, K and Macas, A and Kupcinskiene, K and Lukosiene, L and Janciauskas, D and Poskiene, L and Vitkauskiene, A and Ianiro, G and Gasbarrini, A and Kiudelis, G and Kupcinskas, J}, title = {Fecal Microbiome Transplantation for Recurrent CDI: Treatment Efficacy and Safety with Oral Capsules.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {34}, number = {2}, pages = {199-204}, doi = {10.15403/jgld-5990}, pmid = {40580532}, issn = {1842-1121}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; Male ; Female ; Retrospective Studies ; Middle Aged ; Treatment Outcome ; Administration, Oral ; *Clostridium Infections/therapy/microbiology/diagnosis ; Aged ; Capsules ; Recurrence ; *Clostridioides difficile ; Adult ; Anti-Bacterial Agents/administration &amp; dosage ; Time Factors ; Feces/microbiology ; }, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation is an effective treatment method for recurrent Clostridioides difficile infection. Widely used enteric tube and colonoscopy methods demonstrate excellent efficacy and safety results. Recent data suggest that new fecal microbiota transplantation methods using oral capsules may provide a less invasive approach. In this study, we aimed to compare primary fecal microbiota transplantation efficacy as well as short- and long-term safety of two different administration routes: oral capsules and enteric tube.<br><br>METHODS: This retrospective study included 60 consecutive patients who underwent fecal microbiota transplantation for recurrent Clostridioides difficile infection. Thirty participants received 50 oral capsules containing frozen material for a single day and 30 patients received fecal microbiota transplantation via nasoenteric tube. All patients received standard treatment with oral vancomycin 500 mg q.i.d. for at least five days before the procedure. After intervention, patients were followed up for at least six months. Data on Clostridioides difficile infection recurrences and health status were collected and analyzed.<br><br>RESULTS: The oral capsules group consisted of 30 patients. Among them, 22 (73.3%) participants experienced resolution of symptoms after a single fecal microbiota transplantation, while eight (26.7%) patients developed recurrent diarrhea within eight weeks. The other 30 patients received treatment via nasoenteric tube. Among them, 24 (80%) patients were cured after a single fecal microbiota transplantation, while six (20%) experienced recurrent disease within eight weeks. The primary efficacy did not show significant differences between the two groups (p=0.85). Throughout the follow-up period, no serious adverse events or fecal microbiota transplantation related deaths were reported in both groups.<br><br>CONCLUSIONS: Fecal microbiota transplantation with frozen oral capsules is a safe, less invasive method with comparable efficacy to nasoenteric administration route.}, }
@article {pmid40579140, year = {2025}, author = {Zhu, Y and Zhu, Z and Wu, P}, title = {[Pentosan polysulfate alleviates cyclophosphamide-induced interstitial cystitis/bladder pain syndrome in mice by modulating gut microbiota and bile acid metabolism].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {45}, number = {6}, pages = {1270-1279}, pmid = {40579140}, issn = {1673-4254}, support = {82370782//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Cystitis, Interstitial/chemically induced/drug therapy ; *Gastrointestinal Microbiome/drug effects ; *Pentosan Sulfuric Polyester/pharmacology/therapeutic use ; Cyclophosphamide/adverse effects ; Mice, Inbred C57BL ; Female ; Mice ; *Bile Acids and Salts/metabolism ; Urinary Bladder ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {OBJECTIVES: To investigate the therapeutic efficacy and mechanism of pentosan polysulfate (PPS) for cyclophosphamide (CYP)-induced interstitial cystitis/bladder pain syndrome (IC/BPS) in mice.<br><br>METHODS: Female C57BL/6 mice (6-8 weeks old) were randomized into control group, PPS treatment (25 mg/kg via gavage for 3 weeks) group, CYP treatment (3 separate intraperitoneal injections at 50 mg/kg in week 4), and CYP+PPS treatment group. Gut microbiota alterations of the mice were analyzed using 16S rDNA sequencing and non-targeted metabolomics. Fecal microbiota transplantation (FMT) was performed in CYP-treated recipient mice and those treated with both CYP and PPS. In the in vitro experiment, LPS-stimulated human bladder epithelial cells (SV-HUC-1) were used to assess the effects of deoxycholic acid (DCA) and TGR5 signaling inhibitor SBI-115 on barrier functions of bladder epithelial cells.<br><br>RESULTS: PPS treatment significantly improved the mechanical pain thresholds, restored the urodynamic parameters, and attenuated bladder inflammation and barrier dysfunction in CYP-treated mice. Mechanistically, PPS enriched the abundance of Eubacterium xylanophilum and increased DCA levels in the intestines of CYP-treated mice. FMT experiments confirmed microbiota-dependent therapeutic effects of PPS, shown by reduced bladder pathology in the recipient mice treated with both CYP and PPS. In SV-HUC-1 cells, DCA obviously alleviated LPS-induced inflammation and barrier disruption, and treatment with SBI-115 abolished these protective effects of DCA.<br><br>CONCLUSIONS: PPS ameliorates IC/BPS in mice by remodeling gut microbiota to enhance DCA production and activate TGR5 signaling, suggesting a novel microbiota-bile acid-TGR5 axis that mediates the therapeutic effect of PPS and a therapeutic strategy for IC/BPS by targeting gut-bladder crosstalk.}, }
@article {pmid40578039, year = {2025}, author = {Wen, Y and Li, M and Hao, Y and Peng, J and Wei, X and Zhang, Z and Liu, B and Wang, Y and Peng, T and Ma, Y}, title = {HDAC/NF-κB signaling pathway mediates gut microbiota dysbiosis in rheumatoid arthritis: Intervention mechanisms of Fengshining decoction.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {145}, number = {}, pages = {156976}, doi = {10.1016/j.phymed.2025.156976}, pmid = {40578039}, issn = {1618-095X}, abstract = {BACKGROUND: Gut microbiota dysbiosis has been associated with the development of rheumatoid arthritis (RA). Fengshining (FSN) is a traditional Chinese medicine decoction that can effectively alleviate RA. However, how FSN modulates the gut microbiota to mitigate RA has not been comprehensively studied. This study evaluated the gut microecological mechanisms underlying FSN's effects on RA, focusing on the impact of gut-derived short-chain fatty acids (SCFAs), specifically butyrate, in RA treatment.<br><br>METHODS: The pharmacological effects of FSN on type II collagen-induced arthritis (CIA) in mice were assessed via pathological indicators, metagenomics, and metabolomics analyses. Furthermore, the impact of FSN on gut microbiota and metabolic profiles was also evaluated. Moreover, a pseudo-germ-free CIA model was established to validate whether exogenous butyrate alleviates RA. This study also elucidated whether fecal microbiota transplantation (FMT) from FSN-treated mice could mitigate RA symptoms.<br><br>RESULTS: The data showed that FSN markedly alleviated CIA symptoms and reduced serum inflammatory cytokine levels. Metagenomic and metabolomic analyses revealed that FSN-enriched SCFA-producing bacteria, including Butyrivibrio, Faecalicatena, and Lacrimispora. Furthermore, FSN increased the activity of carbohydrate metabolism-related enzymes and upregulated the expression patterns of homologous protein families. Moreover, exogenous butyrate supplementation suppressed pro-inflammatory factors, modulating immune responses, and enhanced intestinal barrier function. Further, Western blot analysis validated that FSN inhibited the HDAC/NF-&#x3ba;B pathway.<br><br>CONCLUSION: This study indicated that the gut microecological mechanism of FSN might be associated with its herbal components, which regulate gut microbiota diversity, restore the intestinal barrier, and boost microbial metabolite production. Furthermore, butyrate was observed to modulate intestinal mucosa, inhibit inflammatory responses, repair the intestinal barrier, and mitigate joint damage, thus alleviating RA symptoms.}, }
@article {pmid40576702, year = {2025}, author = {Shtrozberg, S and Bazzichi, L and Sarzi-Puttini, P and Aloush, V and Ablin, JN}, title = {Is the gut microbiome of importance in fibromyalgia? A critical review of emerging evidence.}, journal = {Clinical and experimental rheumatology}, volume = {43}, number = {6}, pages = {990-998}, doi = {10.55563/clinexprheumatol/pmajsv}, pmid = {40576702}, issn = {0392-856X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Fibromyalgia/microbiology/physiopathology/therapy/diagnosis ; Animals ; Probiotics/therapeutic use ; Nutritional Status ; Dysbiosis ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {Fibromyalgia (FM) is a multifaceted chronic pain syndrome, predominantly affecting women, and characterised by a constellation of symptoms including diffuse musculoskeletal pain, fatigue, cognitive impairment and poor sleep quality. Its complex pathophysiology likely involves genetic, environmental and psychosocial factors. Recent studies have raised the possibility that the gut microbiome may influence FM symptoms via the gut-brain axis, although this hypothesis remains unconfirmed. This review aims to explore potential associations between gut microbiome alterations, nutrition, and FM, with particular attention to the limitations of current evidence. While certain studies have reported differences in the gut microbiota composition of patients with FM, these findings are preliminary and often derive from small, heterogeneous cohorts. Likewise, faecal microbiota transplantation studies in animals and limited human trials suggest a possible link to pain sensitivity, but further validation is needed.Nutritional interventions, including prebiotics, probiotics and specific dietary strategies, have shown early promise in modulating gut microbiota and alleviating FM symptoms. Nutrients such as magnesium, selenium and omega-3 fatty acids, as well as antioxidant compounds, may influence pain and inflammation pathways, but definitive clinical recommendations are lacking. Given the emerging nature of this field, larger and better-controlled studies are required to clarify the role of the gut microbiome and nutrition in FM. A multidisciplinary management strategy, integrating nutritional approaches cautiously and based on individual profiles, may offer benefits, although no standard therapeutic guidelines currently exist.}, }
@article {pmid40576662, year = {2025}, author = {Goldschmidt, I and Kramer, M and Junge, N and Ouro-Djobo, N and Poets, A and Rathert, M and Geffers, R and Baumann, U and Hartleben, B and Schulze, KD and Woltemate, S and Vital, M}, title = {Short- and long-term development of gut microbiota in children after liver transplantation - a prospective observational trial.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {}, number = {}, pages = {}, doi = {10.1097/LVT.0000000000000659}, pmid = {40576662}, issn = {1527-6473}, abstract = {In children, little is known on gut microbiota (GM) in end-stage liver disease and its association with graft function after pediatric liver transplantation (pLT). We analyzed GM composition and function in children before pLT, longitudinally post-pLT and in long-term survivors (LT-pLT) in order to assess the impact of disease severity, treatment and pLT on GM and delineate associations with graft and patient health. Fecal samples (FS) of 29 children (17f, age 2.6 [0.2-15.7] years) awaiting pLT were included with longitudinal follow-ups until 12M post-transplant in 18, and compared with 38 LT-pLT (21f, age 11 [2.7-17.7] years, 7.8 [1.0-17.0] years post-pLT) and 94 healthy controls (HC). Samples were analyzed using quantitative 16S rRNA gene analyses combined with shotgun metagenomics (subset of samples). Pre-pLT patients showed reduced alpha-diversities and altered GM composition compared with LT-pLT and HC, associated with disease severity and anti-pruritic treatment with Rifampicin. Dysbiosis increased after pLT and started to recover after 3M. Although bacterial concentrations, alpha diversity and gene richness increased post-pLT, levels remained below those of HC. Abundances of key functions, e.g. the capacity to synthesize butyrate, also remained reduced. Quantitative analyses revealed true extent of differences between patients and HC that were underestimated using relative abundance data. GM diversity and functional capacities correlated negatively with transaminase levels mid- and long-term after pLT. Random Forest analyses based on GM were able to predict hepatocellular damage at high accuracy (AUC: 0.89). We provide comprehensive, quantitative insights into GM composition and function before and after pLT. A link between GM alterations with (long-term) graft health was uncovered providing possible targets to modulate GM function in order to increase graft and patient health.}, }
@article {pmid40575995, year = {2025}, author = {Zhang, D and Dong, B and Chen, J and Zhang, Z and Zeng, W and Liao, L and Xiong, X and Qin, X and Fan, X}, title = {Fecal Microbiota Transplantation Modulates Th17/Treg Balance via JAK/STAT Pathway in ARDS Rats.}, journal = {Advanced biology}, volume = {}, number = {}, pages = {e00028}, doi = {10.1002/adbi.202500028}, pmid = {40575995}, issn = {2701-0198}, support = {2022NSFSC0046//Natural Science Foundation of Sichuan Province of China/ ; 2022QN074//Southwest Medical University School-Level Project/ ; 2023JYJ049//Luzhou City Science and Technology Program Project/ ; LRYGCC202120//Guangxi Key Specialty Construction Project Funding, Liuzhou City People's Hospital High-Level Talent Research Startup Fund/ ; lry202408//Liuzhou People's Hospital In-house Project Funding/ ; lry202409//Liuzhou People's Hospital In-house Project Funding/ ; lry202411//Liuzhou People's Hospital In-house Project Funding/ ; GXZYB20240601//Guangxi Autonomous Region Traditional Chinese Medicine Self-Funded Project/ ; 2024YB0103B003//Liuzhou City Science and Technology Program Project/ ; }, abstract = {This study evaluated the therapeutic effects of fecal microbiota transplantation (FMT) on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) in rats. The study focused on the balance of T-helper 17 (Th17) and regulatory T (Treg) cells, as well as the modulation of the JAK/STAT pathway. This study established a rat ARDS model using intranasal LPS instillation, administering interventions such as FMT, Treg cell depletion, and JAK inhibitors. Assessments included histopathological examination of lung and intestinal tissues, flow cytometry for Th17 and Treg cell proportions, qPCR and Western blot for gene and protein expression, ELISA for inflammatory cytokines, and correlation analysis using Spearman's method for cytokine-immune cell interactions. Results indicated that FMT and JAK inhibitors significantly reduce lung damage induced by LPS, reduced alveolar destruction and inflammation, restored Th17/Treg balance, and inhibited JAK/STAT pathway activity. Notably, FMT decreased pro-inflammatory cytokines (IL-2, IL-6, IL-8, IL-17A, IL-23, TGF-β1) and increased anti-inflammatory cytokines (IL-10, IL-35) in serum. Spearman correlation analysis indicated that FMT restored immune balance by modulating the interactions between cytokines and immune cells. In conclusion, FMT effectively alleviates lung and intestinal injury in LPS-induced ARDS rat models by modulating Th17/Treg balance and inhibiting JAK/STAT pathway activity, demonstrating promising therapeutic potential for ARDS treatment.}, }
@article {pmid40575647, year = {2025}, author = {Tüsüz Önata, E and Özdemir, &#xd6;}, title = {Microbiome, dysbiosis and use of probiotics in various diseases.}, journal = {World journal of virology}, volume = {14}, number = {2}, pages = {99574}, pmid = {40575647}, issn = {2220-3249}, abstract = {The community of microorganisms that colonize certain areas of the human body is called microbiota. Microorganisms such as bacteria, fungi and viruses make up the microbiota. The sum of the genomes of these microorganisms and microorganisms refers to the microbiome. It has been shown that microbiota has important effects such as protecting the organ from pathogens, contributing to metabolic functions (such as vitamin synthesis, carbohydrate digestion) and providing immunoregulation. Dysbiosis refers to compositional and functional changes in the microbiota. At the beginning of the 21[st] century, numerous studies have investigated the human microbiota and its imbalance in relation to various diseases and found that dysbiosis is associated with many diseases. The aim of this mini-review article is to provide brief information about dysbiosis and its care and to raise awareness.}, }
@article {pmid40575364, year = {2025}, author = {Bangolo, A and Amoozgar, B and Habibi, M and Simms, E and Nagesh, VK and Wadhwani, S and Wadhwani, N and Auda, A and Elias, D and Mansour, C and Abbott, R and Jebara, N and Zhang, L and Gill, S and Ahmed, K and Ip, A and Goy, A and Cho, C}, title = {Exploring the gut microbiome's influence on cancer-associated anemia: Mechanisms, clinical challenges, and innovative therapies.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {16}, number = {2}, pages = {105375}, pmid = {40575364}, issn = {2150-5349}, abstract = {BACKGROUND: Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies, which stems from the direct effects of malignancy, treatment-induced toxicities, and systemic inflammation. It affects patients' survival, functional status, and quality of life profoundly. Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia. The gut microbiota, through its intricate interplay with iron metabolism, inflammatory pathways, and immune modulation, may either exacerbate or ameliorate anemia depending on its composition, and functional integrity. Dysbiosis, characterized by disruption in the gut microbial ecosystem, is very common in cancer patients. This microbial imbalance is implicated in anemia causation through diminished iron absorption, persistent low-grade inflammation, and suppression of erythropoiesis.<br><br>AIM: To consolidate current evidence regarding the interplay between gut microbiome and anemia in the setting of malignancies. It aims to provide a detailed exploration of the mechanistic links between dysbiosis and anemia, identifies unique challenges associated with various cancer types, and evaluates the efficacy of microbiome-focused therapies. Through this integrative approach, the review seeks to establish a foundation for innovative clinical strategies aimed at mitigating anemia and improving patient outcomes in oncology.<br><br>METHODS: A literature search was performed using multiple databases, including Google Scholar, PubMed, Scopus, and Web of Science, using a combination of keywords and Boolean operators to refine results. Keywords included "cancer-associated anemia", "gut microbiome", "intestinal microbiota", "iron metabolism", "gut dysbiosis", "short-chain fatty acids", "hematopoiesis", "probiotics", "prebiotics", and "fecal microbiota transplantation". Articles published in English between 2000 and December 2024 were included, with a focus on contemporary and relevant findings.<br><br>RESULTS: Therapeutic strategies aimed at restoration of gut microbial homeostasis, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), can inhibit anemia-causing pathways by enhancing microbial diversity, suppressing detrimental flora, reducing systemic inflammation and optimizing nutrient absorption.<br><br>CONCLUSION: Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients. Microbiome-centered interventions, such as probiotics, prebiotics, dietary modifications, and FMT, have shown efficacy in restoring microbial balance, reducing inflammation, and enhancing nutrient bioavailability. Emerging approaches, including engineered probiotics and bacteriophage therapies, are promising precision-based, customizable solutions for various microbiome compositions and imbalances. Future research should focus on integrating microbiome-targeted strategies with established anemia therapies.}, }
@article {pmid40574876, year = {2025}, author = {Odenwald, MA and Ramaswamy, R and Lin, H and Lehmann, C and Moran, A and Mullowney, MW and Sidebottom, AM and Hernandez, A and McMillin, M and Rose, A and Moran, D and Little, J and Sulakhe, D and D'Souza, M and Woodson, C and Tanveer, T and de Porto, A and Dylla, N and Sundararajan, A and Burgo, V and Cantoral, J and Jadczak, C and Adler, E and Aronsohn, A and Pamer, EG and Rinella, ME}, title = {Fecal Butyrate and Deoxycholic Acid Concentrations Correlate With Mortality in Patients With Liver Disease.}, journal = {Gastro hep advances}, volume = {4}, number = {8}, pages = {100695}, pmid = {40574876}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: The intestinal microbiome produces metabolites, including short chain fatty acids (SCFAs) and secondary bile acids (BAs), that impact host physiology. Loss of intestinal microbiome diversity is associated with cirrhosis progression, but the impact of microbiome-associated metabolites on liver disease remains largely undefined. We aimed to correlate fecal metabolite concentrations with the severity and progression of liver disease.<br><br>METHODS: In this cross-sectional study, fecal samples from patients hospitalized with liver disease were analyzed by shotgun metagenomic sequencing to determine microbiome compositions and targeted mass spectrometry to quantify SCFAs and BAs. Random survival forest and logistic regression models identified clinical, metagenomic, and metabolomic features associated with rehospitalization and survival.<br><br>RESULTS: This cross-sectional study included 24 chronic liver disease, 18 compensated cirrhosis, 225 decompensated cirrhosis and 40 acute-on-chronic liver failure patients and 27 control fecal donors. Microbiome sequencing and metabolite profiling correlated microbial diversity and SCFA and BA concentrations with liver disease severity. Butyrate and deoxycholic acid (DCA) were more important features than individual microbial species in random survival forest models predicting 30-day transplant-free survival, and low butyrate and DCA were associated with 30-day mortality (P < .0001). After controlling for model for end stage liver disease (MELD)-sodium score, disease stage, age and gender, low fecal concentrations of butyrate and DCA remained significant risk factors for death (Cox 1.38, P = .027). Bacterial species associated with butyrate and DCA concentrations included Bifidobacterium spp. and F. prausnitzii.<br><br>CONCLUSION: Mass spectrometry rapidly identifies patients with low fecal butyrate and DCA concentrations who are at increased risk of 30-day mortality. These findings set the stage for clinical trials of microbiome reconstitution with butyrate and DCA-producing bacterial species.}, }
@article {pmid40574831, year = {2025}, author = {Guo, X and Wang, K and Liu, Q and Baran, N and Ma, W}, title = {The gut-immune axis in primary immune thrombocytopenia (ITP): a paradigm shifts in treatment approaches.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1595977}, pmid = {40574831}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Purpura, Thrombocytopenic, Idiopathic/therapy/immunology/microbiology ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Animals ; Blood Platelets/immunology ; Probiotics/therapeutic use ; }, abstract = {Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet destruction and impaired production, leading to bleeding risk. While immunosuppressive therapies are standard, many patients experience relapses or refractory disease, highlighting the need for novel approaches. Emerging evidence suggests the gut microbiota plays a role in immune regulation, yet its impact on ITP remains unclear. Dysbiosis has been linked to immune dysfunction in other autoimmune diseases, but whether it drives or results from immune dysregulation in ITP is debated. This review explores the gut-immune axis in ITP, focusing on microbiota-driven immune modulation, cytokine signaling, and platelet homeostasis. We assess microbiota-targeted interventions, including fecal microbiota transplantation (FMT), probiotics, and dietary modifications, while addressing key controversies and knowledge gaps. Advances in microbiome sequencing and artificial intelligence may facilitate personalized interventions. Standardizing microbiota-based diagnostics and validating their efficacy in clinical trials are crucial for their integration into ITP management. Bridging these gaps may lead to microbiota-driven strategies that enhance immune regulation and improve patient outcomes.}, }
@article {pmid40574570, year = {2025}, author = {Yang, D and Yang, X and Zhou, Y and Wang, H and Wang, R}, title = {Fecal Microbiota Transplantation from Noni Fruit Phenolic-Rich Extract Intervention Mouse Donors Ameliorates Lipid Metabolism Disorder by Regulating the FXR-FGF15 Pathway in a Gut Microbiota-Dependent Manner.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c05184}, pmid = {40574570}, issn = {1520-5118}, abstract = {Noni fruit phenolic-rich extract (NFE) has been confirmed to alleviate lipid metabolism disturbance, with emerging evidence implicating bile acids (BAs) metabolism in a gut microbiota-dependent manner in mediating the effect. The effect and potential mechanism of fecal microbiota transplantation from NFE intervention mouse donors (FMT-NFE) on lipid metabolism disorder were investigated. The results reveal FMT-NFE intervention regulated the body weight, lipid profile levels, and liver damage. FMT-NFE intervention upgraded the abundance of bile salt hydrolase (BSH)-expressing bacteria and short-chain fatty acid (SCFA)-producing bacteria in feces, which is accompanied by changes of BSH activity and BAs profile as well as elevation of the SCFA level. Moreover, western blotting and immunofluorescence results confirmed the intestinal FXR-FGF15 pathway was activated by FMT-NFE intervention, which was accompanied by activation of the liver FXR and inhibition of CYP7A1 expression to control cholesterol-to-BAs conversion. These findings underscore the mechanisms behind maintaining BAs and lipid metabolism homeostasis of NFE.}, }
@article {pmid40573435, year = {2025}, author = {Ajileye, TG and Akinleye, TE and Faleye, TOC and De Coninck, L and George, UE and Onoja, AB and Agbaje, ST and Ifeorah, IM and Olayinka, OA and Oni, EI and Oragwa, AO and Popoola, BO and Olayinka, OT and Osasona, OG and George, OA and Ajayi, PG and Suleiman, AA and Muhammad, AI and Komolafe, I and Adeniji, AJ and Matthijnssens, J and Adewumi, MO}, title = {Ten Previously Unassigned Human Cosavirus Genotypes Detected in Feces of Children with Non-Polio Acute Flaccid Paralysis in Nigeria in 2020.}, journal = {Viruses}, volume = {17}, number = {6}, pages = {}, doi = {10.3390/v17060844}, pmid = {40573435}, issn = {1999-4915}, mesh = {Humans ; *Feces/virology ; Nigeria/epidemiology ; Phylogeny ; *Genotype ; Child ; Child, Preschool ; *Picornaviridae/genetics/classification/isolation &amp; purification ; Genome, Viral ; Infant ; *Picornaviridae Infections/virology/epidemiology ; Genetic Variation ; Adolescent ; Female ; Male ; Metagenomics ; *Paralysis/virology ; }, abstract = {Since its discovery via metagenomics in 2008, human cosavirus (HCoSV) has been detected in the cerebrospinal fluid (CSF) and feces of humans with meningitis, acute flaccid paralysis (AFP), and acute gastroenteritis. To date, 34 HCoSV genotypes have been documented by the Picornaviridae study group. However, the documented genetic diversity of HCoSV in Nigeria is limited. Here we describe the genetic diversity of HCoSV in Nigeria using a metagenomics approach. Archived and anonymized fecal specimens from children (under 15 years old) diagnosed with non-polio AFP from five states in Nigeria were analyzed. Virus-like particles were purified from 55 pools (made from 254 samples) using the NetoVIR protocol. Pools were subjected to nucleic acid extraction and metagenomic sequencing. Reads were trimmed and assembled, and contigs classified as HCoSV were subjected to phylogenetic, pairwise identity, recombination analysis, and, when necessary, immuno-informatics and capsid structure prediction. Fifteen pools yielded 23 genomes of HCoSV. Phylogenetic and pairwise identity analysis showed that all belonged to four species (eleven, three, three, and six members of Cosavirus asiani, Cosavirus bepakis, Cosavirus depakis, and Cosavirus eaustrali, respectively) and seventeen genotypes. Ten genomes belong to seven (HCoSV-A3/A10, A15, A17, A19, A24, D3, and E1) previously assigned genotypes, while the remaining thirteen genomes belonged to ten newly proposed genotypes across the four HCoSV species, based on the near-complete VP1 region (VP1*) of the cosavirus genome. Our analysis suggests the existence of at least seven and eight Cosavirus bepakis and Cosavirus eaustrali genotypes, respectively (including those described here). We report the first near-complete genomes of Cosavirus bepakis and Cosavirus depakis from Nigeria, which contributes to the increasing knowledge of the diversity of HCoSV, raising the number of tentative genotypes from 34 to over 40. Our findings suggest that the genetic diversity of HCoSV might be broader than is currently documented, highlighting the need for enhanced surveillance.}, }
@article {pmid40573341, year = {2025}, author = {Hu, J and Zhang, Q and Liu, D and Cui, X and Wang, Q and Gong, W and Wang, X}, title = {Inhibition of Bovine Enterovirus Infection by Magnolol via Modulating the Gut Microbiota in Mice.}, journal = {Viruses}, volume = {17}, number = {6}, pages = {}, doi = {10.3390/v17060750}, pmid = {40573341}, issn = {1999-4915}, support = {2016YFD0500904 and 2017YFD0500104//National Key Research &amp; Development Program/ ; }, mesh = {Animals ; *Lignans/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Biphenyl Compounds/pharmacology/therapeutic use ; *Enterovirus Infections/drug therapy/virology/veterinary/microbiology ; Cattle ; Disease Models, Animal ; Feces/microbiology ; Fecal Microbiota Transplantation ; *Antiviral Agents/pharmacology ; Viral Load/drug effects ; Enterovirus/drug effects ; }, abstract = {Bovine enterovirus (BEV) infection is one of the important infectious diseases that cause digestive and respiratory symptoms in cattle, posing a significant threat to the cattle industry. Currently, no vaccines or therapeutic drugs are available for this disease. In our study, we utilized a mouse model to investigate the effects of BEV infection on the gut microbiota and examine the therapeutic potential of magnolol (Mag), a polyphenolic bioactive substance, in terms of BEV infection. BEV infection significantly altered the microbiota composition, where the abundance of some beneficial bacteria, such as Lactobacillaceae and Lactobacillus, was markedly reduced. Mag effectively inhibited BEV infection in vivo. Upon BEV infection, Mag treatment reduced the α-diversity of the microbiota, with statistically significant differences on day 3 post-infection compared to the Mag-untreated group. More interestingly, Mag treatment significantly reversed the effect of BEV infection on the Lactobacillaceae and Lactobacillus abundance, indicating that Mag positively regulates beneficial bacteria. The fecal microbiota transplantation (FMT) experiment demonstrated that feces from Mag-treated mice significantly decreased the virus loads in the small intestine samples of BEV-infected mice. These findings demonstrate the interaction between BEV infection and the gut microbiota and highlight the important regulatory role of the gut microbiota in Mag's anti-BEV effects, opening up a new avenue for preventing and controlling BEV infection via targeted modulation of the gut microbiota.}, }
@article {pmid40573072, year = {2025}, author = {Wakino, S and Hasegawa, K and Tamaki, M and Minato, M and Inagaki, T}, title = {Kidney-Gut Axis in Chronic Kidney Disease: Therapeutic Perspectives from Microbiota Modulation and Nutrition.}, journal = {Nutrients}, volume = {17}, number = {12}, pages = {}, doi = {10.3390/nu17121961}, pmid = {40573072}, issn = {2072-6643}, mesh = {Humans ; *Renal Insufficiency, Chronic/microbiology/therapy/physiopathology ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy/microbiology ; Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; *Kidney/physiopathology ; Synbiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Uremia/microbiology ; *Nutrition Therapy/methods ; }, abstract = {Chronic kidney disease (CKD) has a high prevalence worldwide, with an increasing incidence. One of the mechanisms of CKD progression involves a disordered inter-organ relationship between the kidneys and the intestine, known as the kidney-gut axis. In CKD, two pathological gut conditions-disturbed gut microbiota composition called uremic dysbiosis and leaky gut-contribute to the progression of CKD. Dysbiosis is associated with the increased production of gut-derived uremic toxins, leaky gut, and chronic systemic inflammation, leading to worsening uremia, which in turn aggravates the gut condition. This vicious cycle should be a target of the therapeutic strategy against CKD. The modulation of uremic dysbiosis, including prebiotics, probiotics, and synbiotics, has been a typical treatment approach, although clinical evidence for their efficacy has been insufficient. Some non-antibiotic drugs have an impact on human gut bacteria that are believed to play a role in their clinical efficacy on kidney function. Nutrition therapies, including a low-protein diet, dietary fiber, a Mediterranean diet, and whole grains, positively influence gut microbiota composition and have been linked to a decreased risk of CKD. Novel strategies are currently being explored, involving the use of postbiotics, microbiome sequencing techniques, and fecal microbiota transplantation, although clinical application remains to be tested. Human trials investigating the above-mentioned interventions remain inconclusive due to several limitations, including dietary variability and genetic factors. Future research should focus on the development of more effective probiotics, prebiotics, and microbial metabolism-modifying drugs, not only for CKD but for other systemic diseases as well.}, }
@article {pmid40572299, year = {2025}, author = {Cintoni, M and Palombaro, M and Zoli, E and D'Agostino, G and Pulcini, G and Leonardi, E and Raoul, P and Rinninella, E and De Maio, F and Capristo, E and Gasbarrini, A and Mele, MC}, title = {The Interplay Between the Gut Microbiota and Colorectal Cancer: A Review of the Literature.}, journal = {Microorganisms}, volume = {13}, number = {6}, pages = {}, pmid = {40572299}, issn = {2076-2607}, abstract = {Lifestyle, diet, and genetics are established risk factors for developing colorectal cancer (CRC). In recent years, the role of the gut microbiota (GM) has been increasingly highlighted in several studies, suggesting an effect on both the disease's pathogenesis and the efficacy and tolerability of treatments. We conducted a search on Medline, aiming to identify published studies exploring the role of the GM in the development and treatment of CRC. Dysbiosis, an imbalance in GM, is common in CRC patients and is associated with precancerous lesions, aggressive tumors, and varied therapy outcomes. Restoring GM balance can reduce treatment complications and may improve prognosis. The review details how GM influences CRC through metabolite production, inflammation modulation, and immune response alteration. Diet significantly impacts GM composition, with processed meats and high-fat diets increasing CRC risk, while fiber-rich diets are protective. The role of the GM in CRC treatments like surgery, chemotherapy, radiotherapy, and immunotherapy is also explored, noting its influence on complications, chemoresistance, and treatment efficacy. Future strategies involving GM modulation through diet, probiotics, and fecal microbiota transplantation (FMT) show promise for CRC prevention and treatment, warranting further research.}, }
@article {pmid40572244, year = {2025}, author = {Roy, S and Alizadeh Bahmani, AH and Davids, M and Herrema, H and Nieuwdorp, M}, title = {Modulating the Gut-Muscle Axis: Increasing SCFA-Producing Gut Microbiota Commensals and Decreasing Endotoxin Production to Mitigate Cancer Cachexia.}, journal = {Microorganisms}, volume = {13}, number = {6}, pages = {}, pmid = {40572244}, issn = {2076-2607}, abstract = {Cancer cachexia is a multi-organ and multifactorial syndrome characterized by muscle wasting (with or without adipose tissue loss) and systemic inflammation in patients with advanced malignancies. Gut microbiota dysbiosis, particularly the depletion of short-chain fatty acid (SCFA)-producing bacteria, may contribute to the progression of cancer cachexia. Studies in both murine models and humans consistently associate cachexia with a decline in SCFA-producing gut microbiota commensals and an overgrowth of pro-inflammatory pathobionts. These microbial imbalances may lead to reduced levels of SCFAs and branched-chain amino acids (BCAAs) and alter the normal bile acid profile. BCAAs and the maintenance of a normal bile acid profile are associated with muscle synthesis and decreased breakdown. While SCFAs (acetate, propionate, and butyrate), contribute to intestinal barrier integrity and immune regulation. SCFA depletion may increase gut permeability, allowing bacterial endotoxins, such as lipopolysaccharide (LPS), to enter the bloodstream. This may lead to chronic inflammation, muscle catabolism, and impairment of anabolic pathways. Interventions targeting gut microbiota in preclinical models have mitigated inflammation and muscle loss. While clinical data are limited, it suggests an improvement in immune functions and better tolerance to anticancer therapies. Current evidence is predominantly derived from cross-sectional studies suggesting associations without causality. Thus, future longitudinal studies are needed to identify biomarkers and optimize personalized therapy.}, }
@article {pmid40572178, year = {2025}, author = {Maniscalco, I and Bartochowski, P and Priori, V and Iancau, SP and De Francesco, M and Innamorati, M and Jagodzinska, N and Giupponi, G and Masucci, L and Conca, A and Mroczek, M}, title = {The Effects of Fecal Microbial Transplantation on the Symptoms in Autism Spectrum Disorder, Gut Microbiota and Metabolites: A Scoping Review.}, journal = {Microorganisms}, volume = {13}, number = {6}, pages = {}, pmid = {40572178}, issn = {2076-2607}, abstract = {The bilateral interaction between the brain and the gut has recently been on the spectrum of researchers' interests, including complex neural, endocrinological, and immunological signaling pathways. The first case reports and clinical studies have already reported that delivering microbes through fecal microbial transplantation (FMT) may alleviate symptoms of psychiatric disorders. Therefore, modifying the gut microbiota through FMT holds promise as a potential treatment for psychiatric diseases. This scoping review assessed studies from PubMed related to FMT in autism spectrum disorder and attention deficit hyperactivity disorder. The evaluation included nine clinical studies and case reports. The beneficial and persistent effect on the autism spectrum disorder (ASD) symptoms has been reported. Also, an increased microflora diversity and altered levels of neurometabolites in serum were identified, albeit with a tendency to return to baseline over time. The microbiome-gut-brain axis could provide new targets for preventing and treating psychiatric disorders. However, a recent large randomized clinical trial has shed light on the previously collected data and suggested a possible contribution of the placebo effect. This highlights the necessity of large randomized double-blind studies to reliably assess the effect of FMT in ASD.}, }
@article {pmid40571138, year = {2025}, author = {Chen, QZ and Shang, JM and Jiang, YQ and Yang, Y and Zang, CX and Ma, JW and Dong, YR and Wang, JR and Zhou, N and Yang, X and Li, FF and Bao, XQ and Zhang, D}, title = {Gut microbial dysbiosis aggravated Parkinson-like pathology induced by MPTP/probenecid.}, journal = {Physiology &amp; behavior}, volume = {}, number = {}, pages = {115008}, doi = {10.1016/j.physbeh.2025.115008}, pmid = {40571138}, issn = {1873-507X}, abstract = {Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by resting tremor, bradykinesia, rigidity and postural instability. Recent studies have proved that gut microbiota (GM) dysbiosis exists in PD patients. However, the causal relationship between gut microbial dysbiosis and pathogenesis of PD remains unexplored. Here, using MPTP/probenecid-induced PD mouse model and an antibiotic cocktail (ABX)-induced pseudo-germ-free status, we observed that GM diversity and abundance significantly decreased in feces of ABX-treated PD mice by 16S rRNA sequencing. Remarkably, gut microbial dysbiosis induced by ABX aggravated GI dysfunction and motor deficits in PD mice. Moreover, ABX treatment caused more severe inflammation, and dopaminergic (DAergic) neuronal loss in both the gut and brain. Further study showed that fecal microbiota transplantation (FMT) corrected gut microbial dysbiosis, along with increased short-chain fatty acids (SCFAs). Additionally, GI and motor dysfunctions were improved, peripheral and central inflammation were also attenuated when PD mice were treated with FMT. These findings revealed that gut microbial dysbiosis could aggravate PD pathological damages, and highlighted that gut microbial dysbiosis might be an important factor that impacts PD pathogenesis through the microbiota-gut-brain axis.}, }
@article {pmid40570572, year = {2025}, author = {Ordóñez, C and Zurita, S and Ramírez, G and Cordeiro, F and Garcia-Matamoros, K and Huaman-Garaicoa, F and Orellana-Manzano, A and Sandoya-Onofre, L and Pogo, J and Carvajal-Aldaz, D}, title = {Are we there yet? Gut microbiota for cancer diagnosis, prognosis and treatment.}, journal = {Seminars in oncology}, volume = {52}, number = {4}, pages = {152376}, doi = {10.1016/j.seminoncol.2025.152376}, pmid = {40570572}, issn = {1532-8708}, abstract = {Cancer remains as one of the leading causes of death worldwide, emphasizing the need for innovative diagnostic and therapeutic tools. The gut microbiota has emerged as a factor that influences cancer progression, prognosis, and treatment outcomes. This review analyzes observational and interventional studies conducted with human subjects over the past 5 years, highlighting significant advancements in gut microbiota research for cancer management. Observational studies consistently demonstrated differences in gut microbial composition between cancer patients and healthy controls. Moreover, microbial diversity, particularly at the species and strain level, correlated significantly with clinical outcomes. Interventional studies showed the potential of probiotics and fecal microbiota transplantation (FMT) as adjuncts in cancer therapy by restoring microbial diversity, reducing inflammation, and alleviating chemotherapy-induced complications. Collectively, these findings suggest the gut microbiota's potential as a tool for cancer care. Future research should focus on standardizing taxonomic-level analyses, optimizing probiotic formulations, and validating FMT/AFMT clinical protocols to fully harness the gut microbiota's diagnostic and therapeutic capabilities in oncology.}, }
@article {pmid40570072, year = {2025}, author = {Shatova, OP and Shestopalov, AV and Zlatnik, EY and Novikova, IA and Goncharova, AS and Maksimov, AY}, title = {The effect of fecal microbiota transplantation on levels of tryptophan metabolites in intestine and serum of gnotobiotic mice.}, journal = {Biomeditsinskaia khimiia}, volume = {71}, number = {3}, pages = {209-216}, doi = {10.18097/PBMCR1554}, pmid = {40570072}, issn = {2310-6972}, mesh = {Animals ; *Tryptophan/metabolism/blood ; Mice ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Germ-Free Life ; Indoles/metabolism/blood ; *Intestines/microbiology ; Feces/microbiology ; Male ; Kynurenine/blood/metabolism ; Quinolinic Acid/metabolism/blood ; }, abstract = {Gut microbiota is one of the key suppliers of tryptophan metabolites, which perform various functions in the host organism, including their role as signaling molecules. Fecal microbiota transplantation (FMT) is widely used as a method for determining the contribution of microorganisms to the content of various metabolites in the holoorganism. In this regard, the aim of our study was to investigate the effect of FMT on the level of tryptophan metabolites in feces and blood in gnotobiotic mice. It was found that both before and after FMT, indole-3-lactate, and quinolinic acid were the dominant tryptophan metabolites in the intestine. FMT increased the content of both indoles (indole-3-acetate, indole-3-acrylate, indole-3-butyrate, indole-3-lactate) and kynurenines (anthranilic and xanthurenic acids) in the intestine. In serum of mice after FMT, indole metabolites (indole-3-butyrate, indole-3-carboxaldehyde, indole-3-lactate, indole-3-propionate) predominantly increased; however, tryptamine and xanthurenic acid also demonstrated a clear increase. The use of FMT demonstrates that the intestinal microbiota is a source of not only indole derivatives of tryptophan, but also metabolites of the kynurenine pathway.}, }
@article {pmid40569502, year = {2025}, author = {Mortezaee, K}, title = {Microbiota interaction with Tregs: a target for colitis.}, journal = {Clinical &amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {}, number = {}, pages = {}, pmid = {40569502}, issn = {1699-3055}, abstract = {Gut-resident microbiota associate with host immune system to promote homeostasis, and regulatory T cells (Tregs) are critical in the maintenance of immune balance. Tregs have immunosuppressive activity, and their presence hampers the development of inflammatory diseases. This review aims to unravel microbiome impact on Tregs in bowel inflammation and harnessing such interaction to combat colitis as a separate disease or a consequence of immune checkpoint inhibitor (ICI) therapy of cancer. Short-chain fatty acids (SCFAs) are microbial-derived metabolites associated positively with Treg generation and maintenance and being effective for hampering bowel inflammation. Treg induction shapes gut microbiota profile and support microorganism colonization in their niche and protect the host from inflammation, while suppression of Treg differentiation and activity directs microbiota-induced Th17 expansion and inducing inflammation. Thus, balancing Treg representation with Th17 cells and Treg reprogramming through manipulation of gut microbiota can offer therapy. Microbiota epithelial attachment/detachment and interaction with antigen-presenting cells (APCs) are important for the final fate of T cell signature. Fecal microbial transplantation (FMT) is a strategy for promoting normobiosis and represents a navel approach to targeting colitis. FMT with appropriate microbiota from healthy donors can reinforce microbial diversity, density and persistence to enrich their environment with transforming growth factor (TGF)-β, induce IL-10 producing APCs and reinforce gut barrier, with all these being effective for recovering Tregs, restoring intestinal homeostasis and hampering colitis. ICI therapy of cancer may predispose subjects to colitis due to the impact on microbiome and reducing Treg population. FMT promotes local Treg reorchestration, being advantageous in cancer patients.}, }
@article {pmid40568731, year = {2025}, author = {Masetti, R and Barbara, G and Muratore, E and Marasco, G and Cremon, C and Marangoni, A and Brigidi, P and Putignani, L and Angelino, G and Quagliarella, F and Galaverna, F and Leardini, D and Lazzarotto, T and Gabelli, M and Savarino, E and Zecca, M and Faraci, M and Prete, A and Biffi, A and Locatelli, F and Merli, P}, title = {Fecal microbiota transplantation for decolonization from multidrug-resistant bacteria in pediatric allogeneic hematopoietic stem cell transplantation recipients: a retrospective real-word data study.}, journal = {Haematologica}, volume = {}, number = {}, pages = {}, doi = {10.3324/haematol.2025.288067}, pmid = {40568731}, issn = {1592-8721}, abstract = {Not available.}, }
@article {pmid40568683, year = {2025}, author = {Wang, C and Fan, Y and Zhang, L and Zhao, Z and Luo, F and Sun, K and Zeng, M and Tian, H and Peng, M and Luo, Y and Zhao, H and He, S and Sun, H}, title = {Deciphering the contributions of fecal microbiota from patients with high-grade glioma to tumor development in a humanized microbiome mouse model of glioma.}, journal = {Neuro-oncology advances}, volume = {7}, number = {1}, pages = {vdaf085}, pmid = {40568683}, issn = {2632-2498}, abstract = {BACKGROUND: Recent studies have revealed associations between gut microbiota and glioma. However, the underlying mechanisms remain poorly understood. This study primarily aims to elucidate the impact of altered gut microbiota on tumor progression in glioma-bearing mice.<br><br>METHODS: Fecal samples were collected from glioma patients and healthy controls to compare the effects of human-derived gut microbiota on glioma development in mice. We also analyzed the associations between these microbiota profiles and plasma metabolites.<br><br>RESULTS: Significant differences were observed in both the composition and diversity of the gut microbiota between glioma patients and healthy controls. Mice transplanted with gut microbiota from high-grade glioma patients (HGG-FMT) exhibited accelerated glioma progression compared to those transplanted with microbiota from healthy individuals (HC-FMT). Specifically, Eisenbergiella, Mailhella, and Merdimonas were significantly enriched in HGG-FMT mice, while Limosilactobacillus and Anaerospora increased in HC-FMT mice. Furthermore, Merdimonas showed a positive correlation with sphingosine, sphingosine 1-phosphate, and D-sphingosine in HGG-FMT mice. Conversely, Limosilactobacillus was positively correlated with stearidonic acid and eicosapentaenoic acid in HC-FMT mice.<br><br>CONCLUSIONS: Our findings demonstrate that gut microbiota from high-grade glioma patients can promote glioma progression in mice, potentially through mechanisms involving sphingosine 1-phosphate. This metabolite may enter the bloodstream and accelerate glioma growth, offering novel insights into glioma pathogenesis and potential treatment options.}, }
@article {pmid40564914, year = {2025}, author = {Wong, JKC and Patel, BK and Tai, YK and Tan, TZ and Khine, WWT and Chen, WC and Kukumberg, M and Ching, J and Lee, LS and Chua, KV and Tan, TY and Wu, KY and Bai, X and Iversen, JN and Purnamawati, K and Abdul Jalil, R and Kumar, AP and Lee, YK and Moochhala, SM and Franco-Obregón, A}, title = {Fecal Microbiota Transplantation from Mice Receiving Magnetic Mitohormesis Treatment Reverses High-Fat Diet-Induced Metabolic and Osteogenic Dysfunction.}, journal = {International journal of molecular sciences}, volume = {26}, number = {12}, pages = {}, doi = {10.3390/ijms26125450}, pmid = {40564914}, issn = {1422-0067}, support = {A-0001177-01-00//iHealthtech Microbiome in Health, Disease and Aging 2018 Joint Research Grant/ ; MOE-T2EP30120-0016//Ministry of Education/ ; NUHSRO/2023/039/RO5+6/Seed-Mar/04//National University Health System/ ; }, mesh = {Animals ; *Diet, High-Fat/adverse effects ; Mice ; *Fecal Microbiota Transplantation/methods ; Male ; *Osteogenesis ; Mice, Inbred C57BL ; Ceramides/metabolism ; Gastrointestinal Microbiome ; *Magnetic Field Therapy/methods ; Liver/metabolism ; *Metabolic Diseases/therapy/etiology/metabolism ; Bone Density ; }, abstract = {This study compared the metabolic consequences of fecal microbiota transplantation (FMT) from donor mice that had been either administered pulsed electromagnetic field (PEMF) therapy or exercised to recipient mice fed a high-fat diet (HFD). Eight weeks of PEMF treatment (10 min/week) enhanced PGC-1α-associated mitochondrial and metabolic gene expression in white and brown adipose to a greater degree than eight weeks of exercise (30-40 min/week). FMT from PEMF-treated donor mice recapitulated these adipogenic adaptations in HFD-fed recipient mice more faithfully than FMT from exercised donors. Direct PEMF treatment altered hepatic phospholipid composition, reducing long-chain ceramides (C16:0) and increasing very long-chain ceramides (C24:0), which could be transferred to PEMF-FMT recipient mice. FMT from PEMF-treated mice was also more effective at recovering glucose tolerance than FMT from exercised mice. PEMF treatment also enhanced bone density in both donor and HFD recipient mice. The gut Firmicutes/Bacteroidetes (F/B) ratio was lowest in both the directly PEMF-exposed and PEMF-FMT recipient mouse groups, consistent with a leaner phenotype. PEMF treatment, either directly applied or via FMT, enhanced adipose thermogenesis, ceramide levels, bone density, hepatic lipids, F/B ratio, and inflammatory blood biomarkers more than exercise. PEMF therapy may represent a non-invasive and non-strenuous method to ameliorate metabolic disorders.}, }
@article {pmid40564903, year = {2025}, author = {Chung, BS and Yang, K and Park, C and Ryu, T}, title = {Prolonged Intestinal Ethanol Absorption and Oxidative Stress: Revisiting the Gut-Liver Axis in Alcohol-Associated Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {12}, pages = {}, doi = {10.3390/ijms26125442}, pmid = {40564903}, issn = {1422-0067}, support = {RS-2023-00238039//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Oxidative Stress/drug effects ; *Ethanol/pharmacokinetics/metabolism ; *Intestinal Absorption ; Animals ; *Liver/metabolism/drug effects ; Gastrointestinal Microbiome ; *Liver Diseases, Alcoholic/metabolism ; Intestinal Mucosa/metabolism ; *Alcoholism/metabolism ; Dysbiosis ; }, abstract = {Chronic alcohol consumption induces oxidative stress not only in the liver but also in the gastrointestinal tract, where prolonged intestinal ethanol absorption plays a pivotal and underrecognized role. This review reframes ethanol pharmacokinetics to emphasize sustained jejunal and ileal uptake, which maintains elevated blood alcohol levels and perpetuates redox imbalance across the gut-liver axis. We integrate recent findings on ethanol-induced barrier dysfunction, CYP2E1-mediated ROS production, microbial dysbiosis, and mitochondrial disruption, proposing that the intestine is an active site of injury and a driver of systemic inflammation. Key mechanistic insights reveal that gut-derived endotoxins, compromised epithelial integrity, and microbiome-mitochondria interactions converge to exacerbate hepatic and extrahepatic damage. We further explore emerging therapeutic strategies-ranging from NAD[+] repletion and probiotics to fecal microbiota transplantation-that target this upstream pathology. Recognizing prolonged intestinal ethanol absorption as a clinically meaningful phase offers new directions for early intervention and redox-based treatment in alcohol-associated disease.}, }
@article {pmid40564111, year = {2025}, author = {Bieganska, EA and Kosinski, P and Wolski, M}, title = {Possible Applications of Fecal Microbiota Transplantation in the Pediatric Population: A Systematic Review.}, journal = {Biomedicines}, volume = {13}, number = {6}, pages = {}, doi = {10.3390/biomedicines13061393}, pmid = {40564111}, issn = {2227-9059}, abstract = {Background: The potential therapeutic role of fecal microbiota transplantation (FMT) in various diseases has been thoroughly studied over the last few decades. However, the majority of studies focus on the adult population, therefore, conclusions regarding the application of FMT in the pediatric population are much less clear. This systematic review aims to summarize the research conducted so far on the efficacy and safety of FMT in the pediatric population, assess the quality of the evidence of its effectiveness, and outline the most promising areas for future research. Methods: We performed a systematic literature search from the index date to 8 June 2024 on the Embase, PubMed, and Web of Science databases. One author screened the resulting 121 articles. Eventually, 35 eligible studies that reported FMT use in seven different diseases were identified. Results: All of the studies assessed FMT as a safe procedure without many serious adverse effects. The best-documented application, which is the only one recommended in official guidelines, is recurrent Clostridioides difficile infection. Other disease entities in which the use of FMT has been studied with good clinical effects are inflammatory bowel disease, allergic colitis, autism, Tourette syndrome, and colonization with multi-drug-resistant organisms. However, it should be noted that the majority of studies are cohort and case-control studies, without randomization, which translates into low evidence quality. In one randomized, controlled trial focusing on the effect of FMT on weight loss in obese individuals, a lack of effect was found. Conclusions: While FMT and subsequent iterations of gut microbiota-targeted interventions hold promising therapeutic potential for various disease entities in the pediatric population, the current evidence behind this conclusion is of low quality. Based on current studies, these methods appear to be both effective and safe. However, further randomized clinical trials are necessary, especially within the pediatric population, for which such studies remain scarce.}, }
@article {pmid40564097, year = {2025}, author = {Severino, A and Porcari, S and Rondinella, D and Capuano, E and Rozera, T and Kaitsas, F and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {The Multi-Faceted Role of Gut Microbiota in Alopecia Areata.}, journal = {Biomedicines}, volume = {13}, number = {6}, pages = {}, doi = {10.3390/biomedicines13061379}, pmid = {40564097}, issn = {2227-9059}, abstract = {Alopecia areata (AA) is a complex autoimmune disorder with multifactorial pathogenesis. Recent research highlights the gut microbiota as a possible key player in AA pathogenesis through the gut-skin axis: gut dysbiosis may disrupt intestinal barrier integrity and immune tolerance by affecting T regulatory cells, potentially contributing to disease onset and progression. The purpose of this review is to analyze the current evidence on the correlation between gut microbiota and AA, dissecting both the pathogenetic role of its alterations in the onset and progression of disease and its potential role as a therapeutic target.}, }
@article {pmid40563141, year = {2025}, author = {Zhang, Y and Qing, J and Saed, YA and Li, Y}, title = {Gut microbiota implication in diabetic kidney disease: mechanisms and novel therapeutic strategies.}, journal = {Renal failure}, volume = {47}, number = {1}, pages = {2517402}, doi = {10.1080/0886022X.2025.2517402}, pmid = {40563141}, issn = {1525-6049}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/complications/microbiology/therapy ; *Diabetic Nephropathies/microbiology/therapy/etiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; *Diabetes Mellitus, Type 2/complications ; Synbiotics/administration &amp; dosage ; Disease Progression ; }, abstract = {Diabetic kidney disease (DKD) is one of the leading causes of chronic kidney disease and end-stage renal disease worldwide, predominantly driven by the rise in type 2 diabetes mellitus. Recent evidence highlights the crucial role of gut microbiota dysbiosis in the development and progression of DKD. Dysbiosis, characterized by a reduction in beneficial short-chain fatty acid-producing bacteria and an increase in pathogenic species such as Proteobacteria and Bacteroides, exacerbates systemic inflammation, insulin resistance, and kidney damage through mechanisms like increased intestinal permeability and the production of pro-inflammatory metabolites like lipopolysaccharides. This review explores the impact of specific bacterial taxa on DKD risk and progression, such as Alistipes, Subdoligranulum, and their interactions with metabolic pathways. Furthermore, we discuss novel therapeutic strategies targeting gut microbiota, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, which have shown promise in ameliorating DKD symptoms. However, the heterogeneity of gut microbiota across individuals and the challenges in treatment standardization call for personalized approaches and further research into the gut-kidney axis.}, }
@article {pmid40563092, year = {2025}, author = {Amimo, JO and Kunyanga, CN and Raev, SA and Kick, M and Micheal, H and Saif, LJ and Vlasova, AN}, title = {Stunting is associated with persistent and transferable alterations in the gut microbiome.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {49}, pmid = {40563092}, issn = {1757-4749}, support = {OPP1117467//Bill and Melinda Gates Foundation/ ; R01A1099451//National Institute of Allergy and Infectious Diseases/ ; }, abstract = {As robust animal models to study the pathophysiology of stunting are absent, we have comparatively characterized the gut microbiota of malnourished/stunted vs. clinically healthy/normal Kenyan toddlers (12-24 months old) and established a gnotobiotic (Gn) pig fecal transplant model to gain understanding of microbial community structure associated with stunting. As expected, the bacterial composition between the two toddler groups was distinct: Actinobacteria was most prevalent in healthy toddlers, whereas Proteobacteria dominated in stunted toddlers. Although the diversity indices showed no significant differences, unique bacterial genera were found in each toddler group: three genera unique to stunted toddlers and ten unique to healthy toddlers, with eight genera shared between the groups. We observed a higher number of enriched bacterial virulence genes in healthy vs. stunted toddlers suggesting that the microbiome plasticity and functional characteristics of the healthy toddlers allow for the pathogen/pathobiont control. In contrast, we noted the presence of more genes associated with antimicrobial-resistance (AMR) bacteria in stunted toddlers, possibly due to early-life antibiotic treatments. Of interest, functional analysis showed that CAZymes associated with carbohydrate biosynthesis, and a few metabolic pathways related to protein/amino acid, carbohydrate and fat catabolism were enriched in stunted toddlers. In contrast carbohydrate degradation CAZymes and numerous anabolic pathways were prevalent in healthy toddlers. These patterns were also evident in the Gn pigs transplanted with stunted/healthy human fecal microbiota (HFM). Overall, our findings suggest that the microbiota transplanted Gn pigs represent a valuable model for studying the infant microbial community structure and the impacts of stunting on the child gut microbiota. Additionally, this is the first study to demonstrate that the healthy vs. stunted microbiota composition and function remained different in the Gn pigs throughout the study. This information and the Gn pig model are vital for developing and testing targeted interventions for malnourished/stunted populations, consequently advancing microbiome-based diagnosis and personalized medicine.}, }
@article {pmid40561430, year = {2025}, author = {Ung, W and Bonavida, B}, title = {Review Article: Fecal Microbiota Transplantation in Melanoma: Mechanisms-Mediated Enhancement of Anti-Tumor Immunotherapy.}, journal = {Critical reviews in oncogenesis}, volume = {30}, number = {2}, pages = {23-35}, doi = {10.1615/CritRevOncog.2025058249}, pmid = {40561430}, issn = {0893-9675}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Melanoma/therapy/immunology/microbiology/etiology ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; Animals ; *Skin Neoplasms/therapy/immunology/microbiology ; }, abstract = {The gut microbiota is integral to human health, influencing nutrition, metabolism, and immunity. Dysbiosis has been implicated in cancer development and resistance to therapies, highlighting the potential of microbiota modulation as a therapeutic strategy. Melanoma, while comprising only 1% of skin cancer diagnoses, accounts for over 80% of skin cancer related deaths, emphasizing the need for innovative approaches to enhance treatment efficacy. Although immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) blockade therapies have significantly improved survival for some melanoma patients, the majority fails to achieve durable responses and often develops long-term resistance to these treatments. Fecal microbiota transplantation (FMT) is emerging as a promising intervention to restore microbial balance and enhance treatment efficacy. This review explores the historical evolution and current applications of FMT in oncology, with a focus on its ability to modulate the gut microbiome, augment antitumor immunity, and overcome resistance to checkpoint blockade therapy in melanoma. Despite its promise, significant challenges remain, including ensuring the safety of the procedure, selecting suitable donors, and addressing regulatory hurdles. Future research aimed at optimizing FMT protocols, identifying key microbial strains, and understanding the mechanisms underlying microbiota-immune interactions will be essential to fully harness the potential of FMT as a transformative adjunct in cancer treatment.}, }
@article {pmid40559778, year = {2025}, author = {Nishigaki, A and Marchesi, JR and Previdelli, RL}, title = {Faecal Microbiota Transplantation as an Adjuvant Treatment for Extraintestinal Disorders: Translating Insights from Human Medicine to Veterinary Practice.}, journal = {Veterinary sciences}, volume = {12}, number = {6}, pages = {}, doi = {10.3390/vetsci12060541}, pmid = {40559778}, issn = {2306-7381}, abstract = {Faecal microbiota transplantation (FMT) has emerged as a transformative therapy in human medicine, particularly for managing recurrent Clostridioides difficile infections and other gastrointestinal (GI) disorders. Beyond the GI tract, FMT has shown potential in addressing extraintestinal conditions in people, including metabolic, immune-mediated, dermatological, neurological, and infectious diseases. Research in people has highlighted its efficacy in decolonising multidrug-resistant organisms in infection, mitigating autoimmune diseases, and improving outcomes in metabolic disorders such as obesity and diabetes. Furthermore, FMT has also been linked to enhanced responses to immunotherapy in cancer and improved management of hepatic and renal conditions. These findings underscore the intricate connections between the gut microbiome and systemic health, opening novel therapeutic avenues. In veterinary medicine, while FMT has demonstrated benefits for GI disorders, its application in extraintestinal diseases remains largely unexplored. Emerging evidence suggests that conditions such as atopic dermatitis, chronic kidney disease, immune-mediated diseases, and behavioural disorders in companion animals could benefit from microbiome-targeted therapies. However, significant gaps in knowledge persist, particularly regarding the long-term safety and efficacy for veterinary applications. This review synthesises findings from human medicine to assess their relevance for veterinary applications and future research.}, }
@article {pmid40559592, year = {2025}, author = {Egrek, S and Knapp, J and Sacheli, R and El Moussaoui, K and Léonard, P and Larranaga Lapique, E and Millon, L and Engelskirchen, S and Detry, O and Linden, A and Hayette, MP}, title = {EmsB Microsatellite Analysis of Echinococcus multilocularis Specimens Isolated from Belgian Patients with Alveolar Echinococcosis and from Animal Hosts.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/pathogens14060584}, pmid = {40559592}, issn = {2076-0817}, mesh = {Animals ; *Echinococcus multilocularis/genetics/isolation &amp; purification/classification ; Humans ; Foxes/parasitology ; *Microsatellite Repeats ; Belgium/epidemiology ; *Echinococcosis/parasitology ; Retrospective Studies ; Zoonoses/parasitology ; *Echinococcosis, Hepatic/parasitology ; Genotype ; Rodentia/parasitology ; Feces/parasitology ; }, abstract = {Alveolar echinococcosis (AE), caused by Echinococcus multilocularis (E. multilocularis), is a severe parasitic zoonosis that is potentially fatal for humans. The parasite is primarily transmitted by wildlife, with red foxes acting as definitive hosts and rodents as intermediate hosts, while humans can become accidental but dead-end hosts. The aim of this study is to use EmsB typing on E. multilocularis isolates from human AE cases and local animals such as foxes and rodents. In this study, retrospective EmsB typing was performed on 39 samples, including 11 tissue samples from 10 patients, 18 fecal swabs from foxes, and 10 tissue samples from rodents. A dendrogram was created to determine the EmsB profiles present. The results showed that all the rodent samples were associated with the EmsB P1 profile (10/10), while the human and fox samples shared the EmsB profile P1 (5/11 humans and 8/18 foxes), a profile near P4 (2/11 humans and 3 foxes), and a profile near P8 (1/11 humans and 1/18 foxes). The study demonstrates that the same EmsB profiles circulate among humans and animals, confirming that wildlife reservoirs play a key role in transmission.}, }
@article {pmid40559436, year = {2025}, author = {Domilescu, I and Miutescu, B and Horhat, FG and Popescu, A and Nica, C and Ghiuchici, AM and Gadour, E and Sîrbu, I and Hutanu, D}, title = {Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review.}, journal = {Metabolites}, volume = {15}, number = {6}, pages = {}, doi = {10.3390/metabo15060412}, pmid = {40559436}, issn = {2218-1989}, abstract = {BACKGROUND AND OBJECTIVES: Rectal cancer management increasingly relies on watch-and-wait strategies after neoadjuvant chemoradiotherapy (nCRT). Accurate, non-invasive prediction of pathological complete response (pCR) remains elusive. Emerging evidence suggests that gut-microbiome composition modulates radio-chemosensitivity. We systematically reviewed primary studies that correlated baseline or on-treatment gut-microbiome features with nCRT response in locally advanced rectal cancer (LARC).<br><br>METHODS: MEDLINE, Embase and PubMed were searched from inception to 30 April 2025. Eligibility required (i) prospective or retrospective human studies of LARC, (ii) faecal or mucosal microbiome profiling by 16S, metagenomics, or metatranscriptomics, and (iii) response assessment using tumour-regression grade or pCR. Narrative synthesis and random-effects proportion meta-analysis were performed where data were homogeneous.<br><br>RESULTS: Twelve studies (n = 1354 unique patients, median sample = 73, range 22-735) met inclusion. Four independent machine-learning models achieved an Area Under the Receiver Operating Characteristic curve AUROC &#x2265; 0.85 for pCR prediction. Consistently enriched taxa in responders included Lachnospiraceae bacterium, Blautia wexlerae, Roseburia spp., and Intestinimonas butyriciproducens. Non-responders showed over-representation of Fusobacterium nucleatum, Bacteroides fragilis, and Prevotella spp. Two studies linked butyrate-producing modules to radiosensitivity, whereas nucleotide-biosynthesis pathways conferred resistance. Pooled pCR rate in patients with a "butyrate-rich" baseline profile was 44% (95% CI 35-54) versus 21% (95% CI 15-29) in controls (I[2] = 18%).<br><br>CONCLUSIONS: Despite heterogeneity, convergent functional and taxonomic signals underpin a microbiome-based radiosensitivity axis in LARC. Multi-centre validation cohorts and intervention trials manipulating these taxa, such as prebiotics or live-biotherapeutics, are warranted before clinical deployment.}, }
@article {pmid40558164, year = {2025}, author = {Han, X and Qin, Y and Guo, J and Huang, W and You, Y and Zhan, J and Yin, Y}, title = {IgA Dysfunction Induced by Early-Lifetime Low-Dose Antibiotics Exposure Aggravates Diet-Induced Metabolic Syndrome.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/antibiotics14060574}, pmid = {40558164}, issn = {2079-6382}, support = {82330017 and 82270610//National Natural Science Foundation/ ; }, abstract = {Background: Low-dose antibiotic contamination in animal feed is a persistent global food safety challenge. Transient early-life exposure to low-dose penicillin (LDP) is known to induce metabolic syndrome (MetS) in adult mice, but the underlying mechanisms are unclear. Introduction: This study investigated the role of gut microbiota (GM) and intestinal immunity in mediating the long-term metabolic effects of early-life LDP exposure. Methods: Mice were exposed to LDP transiently during early life. GM composition was analyzed. Intestinal IgA responses were quantified. Bacterial encroachment, systemic and adipose tissue inflammation, and diet-induced MetS were assessed. Germ-free (GF) mice received GM transplants from LDP-exposed or control mice to test causality and persistence. Results: Early-life LDP exposure significantly disrupted GM composition, particularly in the ileum, in 30-day-old mice. These GM alterations caused persistent suppression of intestinal IgA responses, evidenced by reduced IgA-producing cells and sIgA levels. This suppression was constrained to early-life exposure: transferring LDP-modified GM to GF mice produced only a transient reduction in fecal sIgA. The LDP-induced sIgA reduction decreased IgA binding of bacteria, leading to increased bacterial encroachment and systemic and adipose tissue inflammation. These pathological changes exacerbated diet-induced MetS. Discussion: Our findings demonstrate that early-life LDP exposure induces persistent intestinal IgA deficiency through lasting GM alterations initiated in early development. This deficiency drives bacterial encroachment, inflammation, and ultimately exacerbates MetS. Conclusions: The exacerbation of diet-induced metabolic syndrome by early-life LDP exposure occurs through an intestinal sIgA-dependent pathway triggered by persistent GM disruption. This highlights a critical mechanism linking early-life antibiotic exposure, gut immune dysfunction, and long-term metabolic health, with significant implications for food safety.}, }
@article {pmid40554893, year = {2025}, author = {You, L and Peng, H and Liu, J and Sai, N and Zhao, W and Li, X and Yang, C and Guo, P and Ni, J}, title = {Xiaoer Huanglong pellets remodels the periphery microenvironment to improve attention deficit hyperactivity disorder based on the microbiota-gut-brain axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {145}, number = {}, pages = {157007}, doi = {10.1016/j.phymed.2025.157007}, pmid = {40554893}, issn = {1618-095X}, abstract = {BACKGROUND: Recently, research interest in attention deficit hyperactivity disorder (ADHD) has grown significantly, driven by its increasing incidence and substantial societal impact. Among the various pathogenic mechanisms under investigation, the microbiota-gut-brain axis has emerged as a crucial area of focus. In the context of ADHD treatment, Xiaoer Huanglong Pellets (XRHLP), a traditional Chinese herbal formulation, have demonstrated therapeutic efficacy, although the underlying mechanisms remain partially understood.<br><br>PURPOSE: This study aimed to analyze and compare the therapeutic effects and underlying mechanisms of XRHLP, including gastric release (WR_HL), enteric release (CR_HL), and colon release (JCR_HL) pellets, for ADHD treatment.<br><br>METHODS: This study employed a multi-modal approach to investigate the effects of XRHLP on ADHD. Behavioral assessments combined with Enzyme-linked immunosorbent assay and Western-blot analyses were conducted to evaluate the therapeutic outcomes in model rats with ADHD. Comprehensive profiling of the gut-brain axis was performed using 16S ribosomal RNA sequencing and untargeted and targeted metabolomic analyses. The causal role of the gut microbiota was further validated using fecal microbiota transplantation (FMT).<br><br>RESULTS: WR_HL, CR_HL, and JCR_HL improved ADHD-like behaviors and neurotransmission dysfunction, with JCR_HL exhibiting superior intervention effects compared to WR_HL and CR_HL. These therapeutic effects are mediated through multiple pathways, including the restoration of gut microbial homeostasis, attenuation of inflammatory cascades, and repair of compromised intestinal and blood-brain barrier. The intervention also corrected systemic metabolic imbalances by specifically addressing the abnormalities in amino acid metabolism, neurotransmitter regulation, and short-chain fatty acid production. FMT experiments further confirmed the critical role of microbial modulation in mediating the behavioral and microbial regulatory effects of XRHLP.<br><br>CONCLUSION: In summary, XRHLP exerts anti-ADHD effects by improving the microbiota-gut-brain axis and correcting amino acid metabolic disorders, providing new insights into the molecular mechanisms by which traditional Chinese medicine influences ADHD and offers potential avenues for drug development.}, }
@article {pmid40554061, year = {2025}, author = {Yang, W and Zou, P and He, S and Cui, H and Yang, Z and An, H and Chen, Q and Huang, W and Guo, H and Liu, J and Ling, X and Cao, J and Ao, L}, title = {Perfluorooctane sulfonic acid impairs spermatogenesis via the liver-gut microbiota-testis axis: a central role of chenodeoxycholic acid metabolism.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.06.037}, pmid = {40554061}, issn = {2090-1224}, abstract = {INTRODUCTION: Perfluorooctane sulfonic acid (PFOS) as a global contaminant is ubiquitously presented in the environmental media and human body. The association between PFOS exposure and reduced male fertility has been recently discovered. However, the relevant mechanism remains unexplored.<br><br>OBJECTIVES: Our study aimed to investigate the effect and mechanism of PFOS exposure on male reproductive function.<br><br>METHODS: In a murine PFOS exposure model, single-nucleus transcriptome sequencing was performed to delineate the transcriptomic landscape of mouse testes at the single-cell resolution. We examined the serum metabolomic profile and conducted in-depth analysis of hepatic transcriptome datasets to explore the metabolic connections between liver and testis under PFOS exposure. Through integrating chenodeoxycholic acid intervention, fecal microbiota transplantation (FMT), metagenomic sequencing, testicular metabolome, Ligilactobacillus murinus (L. murinus) metabolome, and administration of L. murinus, we confirmed the role of the liver-gut microbiota-testis axis and screened the critical gut microbiota involved in PFOS-mediated spermatogenic disorders.<br><br>RESULTS: The results showed that PFOS exposure led to spermatogenic arrest and abnormal spermatogenic microenvironment in the mouse testis. The PFOS-repressed hepatic chenodeoxycholic acid (CDCA) synthesis contributed to the reduced serum/testicular levels of essential fatty acid (linoleic acid) and lipid-soluble vitamins (retinol, vitamin D3), which was responsible for the spermatogenic arrest. Beyond this, PFOS-mediated impaired CDCA production decreased the abundance of gut L. murinus, which affected spermatogenesis through the potential involvement of aspartic acid metabolism. For the first time to our knowledge, we comprehensively assessed the effects of PFOS exposure on the spermatogenic process and elucidated the unrecognized role of liver-gut microbiota-testis axis in PFOS-induced abnormal spermatogenesis.<br><br>CONCLUSIONS: The unveiled organ crosstalks provide new insights into the metabolism-disrupting properties, hepatotoxicity, and reproductive toxicity of PFOS, which may facilitate the development of molecule-, metabolite-, and microbe-based strategies for PFOS-induced metabolic diseases and reproductive disorders.}, }
@article {pmid40553742, year = {2025}, author = {Frutkoff, YA and Plotkin, L and Pollak, D and Livovsky, J and Focht, G and Lev-Tzion, R and Ledder, O and Assa, A and Yogev, D and Orlanski-Meyer, E and Broide, E and Kierkuś, J and Kang, B and Weiss, B and Aloi, M and Schwerd, T and Shouval, DS and Bramuzzo, M and Griffiths, AM and Yassour, M and Turner, D}, title = {Whole food diet induces remission in children and young adults with mild-moderate Crohn's disease and is more tolerable than exclusive enteral nutrition: a randomized controlled trial.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2025.06.011}, pmid = {40553742}, issn = {1528-0012}, abstract = {BACKGROUND: Tasty&amp;Healthy (T&amp;H) is a whole-food diet for Crohn's disease (CD), which excludes processed food, gluten, red meat, and dairy, without requiring formula or mandatory ingredients. TASTI-MM was a clinician-blinded, randomized-controlled trial comparing tolerability and effectiveness of T&amp;H vs. exclusive enteral nutrition (EEN).<br><br>METHODS: Patients with biologic-naive mild-moderate CD aged 6-25 years were randomized to either T&amp;H or EEN for 8 weeks, receiving weekly dietary support. Tolerability was evaluated by weekly interviews, questionnaires and intake diaries. Other outcomes included symptomatic remission, Mucosal-Inflammation Non-Invasive (MINI) index, calprotectin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Fecal microbiome was analyzed by metagenomics at baseline, week-4 and week-8. Data were analyzed by the intention-to-treat approach unless specified otherwise.<br><br>RESULTS: Among 83 included patients (41 T&amp;H, 42 EEN; mean age 14.5&#xb1;3.7 years), 88% tolerated T&amp;H vs. 52% for EEN (aOR 7.7 [95%CI 2.4-25]; p<0.001). Calprotectin, CRP and ESR decreased significantly in both groups, with no between-group differences. Symptomatic remission was achieved in 56% of T&amp;H group vs. 38% of the EEN group (aOR 2.5 [0.98-6.3], p=0.1; per-protocol: 67% vs. 76%; p=0.47). Calprotectin <250&#x3bc;g/g was achieved in 34% vs. 33% (aOR 0.97 [0.37-2.6], p=0.84) and MINI<8 in 44% vs. 31% (aOR 1.8 [0.7-4.5]; p=0.33). Microbiome &#x3b1;-diversity improved in the T&amp;H arm and declined in the EEN arm, showing superior species richness at both week-4 and week-8. Species associated with bowel inflammation, such as Ruminococcus gnavus, decreased in T&amp;H and increased in EEN (q<0.001).<br><br>CONCLUSIONS: T&amp;H demonstrated better tolerability than EEN for inducing remission in mild-to-moderate CD, while positively affecting the microbiome (TASTI-MM, NCT#04239248).}, }
@article {pmid40552988, year = {2025}, author = {Park, JM and Beckman, I and Delaney, CL}, title = {Narrative review of the association between gut microbiota and peripheral artery disease.}, journal = {Vascular medicine (London, England)}, volume = {}, number = {}, pages = {1358863X251346062}, doi = {10.1177/1358863X251346062}, pmid = {40552988}, issn = {1477-0377}, abstract = {It has been posited that the inflammatory process seen in atherosclerosis is underpinned by gut dysbiosis. Dysbiosis refers to alterations in the function, composition, and diversity of the human gut microbiota, all of which are influenced by endogenous and exogenous stimuli. Currently there is limited literature describing the association between gut microbiota and peripheral artery disease (PAD). This review summarizes the evidence surrounding the role of gut microbiota in the initiation of atherosclerosis (through direct infection of atherosclerotic plaque or systemic immune response to bacterial products and metabolites) and how dysbiosis may influence the various treatment modalities for PAD, including medical therapy (pharmacotherapy, lifestyle changes, and supervised exercise training) and surgery (endovascular and open revascularization). In particular, the role of short chain fatty acids (SCFAs), the effects of exercise on SCFA-producing and lactic acid bacteria (LAB) and, consequently, the lack of targeted research into dietary interventions and supplementation are highlighted in this review. This review highlights the potential for gut microbiota as not only a therapeutic target in patients with PAD, but also as a diagnostic and screening tool. It is imperative that the focus of future research is on the potential for personalized treatment which targets the gut microbiota (such as synbiotics, postbiotics, nicotinamide adenine dinucleotide (NAD) supplementation, selective antibiotics, resistance exercise, senolytics, and fecal microbial transplantation [FMT]) to be utilized as adjuncts to already existing treatment options for PAD. This review also highlights the potential role of biobanks and analysis of atherosclerotic plaques in further advancing knowledge and research in this area.}, }
@article {pmid40552775, year = {2025}, author = {Yang, T and Shao, Y and Wang, Z and Liu, C and Gu, M}, title = {Epigallocatechin-3-Gallate Attenuates Benign Prostatic Hyperplasia Development via Regulating Firmicutes to Inhibit Gastric Secretion of Insulin-Like Growth Factor-1.}, journal = {Cell biology international}, volume = {}, number = {}, pages = {}, doi = {10.1002/cbin.70032}, pmid = {40552775}, issn = {1095-8355}, support = {//The work was sponsored by the Interdisciplinary Program of Shanghai Jiao Tong University (Project Number YG2024QNB17) and the National Natural Science Foundation of China (Grant Nos. 82170788 and 81900687)./ ; }, abstract = {Benign prostatic hyperplasia (BPH), a prevalent age-related condition in men, is increasingly linked to metabolic syndrome (MetS) and gut microbiota dysbiosis. This study reveals how Firmicutes-dominant microbial imbalance drives BPH progression via IGF-1 signaling and identifies the green tea polyphenol epigallocatechin-3-gallate (EGCG) as a dual-action therapeutic. Using MetS-BPH mouse models and human prostate cell lines, we demonstrated that BPH-associated gut microbiota-particularly elevated Firmicutes and an increased Firmicutes/Bacteroidetes ratio-promotes prostate hyperplasia by upregulating IGF-1. Both BPH mice and recipient mice transplanted with BPH microbiota showed elevated serum and prostate IGF-1 levels, mirroring findings in human BPH patients. Mechanistically, IGF-1 stimulated prostate cell proliferation (RWPE-1/WPMY-1) and suppressed apoptosis via PI3K/AKT/mTOR activation, while the IGF-1 antagonist Linsitinib reversed these effects. EGCG emerged as a potent modulator of this gut-prostate axis: it selectively reduced Firmicutes overgrowth in BPH mice, normalized IGF-1 levels, and inhibited downstream PI3K/AKT/mTOR signaling. In fecal microbiota transplantation experiments, EGCG counteracted IGF-1-driven prostate enlargement and microbial dysbiosis, underscoring its dual role in rebalancing gut flora and blocking growth factor pathways. Our findings position EGCG as a promising intervention for MetS-associated BPH, simultaneously targeting microbial dysbiosis and IGF-1 signaling. This study not only elucidates the Firmicutes-IGF-1 axis in BPH pathogenesis but also highlights the therapeutic potential of dietary polyphenols in metabolic urological disorders.}, }
@article {pmid40552763, year = {2025}, author = {Claypool, J and Lindved, G and Myers, PN and Ward, T and Nielsen, HB and Blount, KF}, title = {Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2520412}, doi = {10.1080/19490976.2025.2520412}, pmid = {40552763}, issn = {1949-0984}, mesh = {Humans ; *Clostridium Infections/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Feces/microbiology ; Male ; *Clostridioides difficile/physiology ; Female ; Middle Aged ; *Bacteria/classification/genetics/isolation &amp; purification ; Adult ; Recurrence ; Aged ; }, abstract = {Live microbiota therapies have shown promise in many gastrointestinal diseases, including in the prevention of recurrent Clostridioides difficile infections (rCDI); however, frameworks for their pharmacokinetic and pharmacodynamic analysis are not fully established. Fecal microbiota, live-jslm (RBL) is the first microbiota-based product approved by the US Food and Drug Administration for the prevention of rCDI and was superior to placebo in the PUNCH™ CD3 phase 3 clinical trial (NCT03244644). In this analysis, deep shotgun metagenomic sequencing was used to assess changes in gut microbiome compositions of participants and engraftment of bacterial clonal populations (i.e. strains) from RBL to recipients. Among RBL responders, gut microbiota shifted toward compositions that resembled healthy donors as early as 1 week after RBL administration; the resulting microbiota compositions included clonal populations that engrafted from RBL to recipients. Engraftment was higher in RBL responders compared with non-responders, and many clonally engrafted populations persisted for ≥ 6 months. Bacteroidia species were among the most effectively engrafted species from RBL. This study utilizes data from a large clinical trial to establish a method with high specificity for exploring clonal engraftment from microbiota-based treatments to facilitate future pharmacokinetic and pharmacodynamic analyses.Clinicaltrials Registration: NCT03244644.}, }
@article {pmid40552153, year = {2025}, author = {Sun, L and Shang, B and Lv, S and Liu, G and Wu, Q and Geng, Y}, title = {Effects of semaglutide on metabolism and gut microbiota in high-fat diet-induced obese mice.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1562896}, pmid = {40552153}, issn = {1663-9812}, abstract = {BACKGROUND: The purpose of this study was to explore how semaglutide, a GLP-1RA, regulates serum metabolism and gut microbiota to improve obesity in mice and whether fecal microbiota transplantation (FMT) can transmit the beneficial effects of semaglutide to recipient mice.<br><br>METHODS: Male C57BL/6J mice were given standard diet (ND), high-fat diet (HFD), or high-fat diet with semaglutide (SHF, 100&#xa0;&#x3bc;g/kg). Fecal microbiota transplantation was used to transplant the fecal suspension supernatant (MT) and bacteria (FMT) from SHF group mice to antibiotic-induced pseudo-germ-free mice.<br><br>RESULTS: Results showed that semaglutide significantly reduced the body weight, body fat, FBG, and insulin levels induced by high-fat diet, and improved insulin resistance and sensitivity damage (p < 0.05). This was achieved by regulating the expression of genes related to lipid metabolism such as Ppar&#x3b1;, Ppar&#x3b3;, Cpt1a, and Pgc1&#x3b1; in the liver and adipose tissue, as well as the appetite-related genes Leptin, Agrp, Npy, and Pomc in the hypothalamus. After stopping semaglutide intervention 4&#xa0;weeks, the body weight of the mice rebounded significantly. Fecal microbiota transplantation could transmit the beneficial effects of semaglutide to recipient mice. Semaglutide and fecal microbiota transplantation affected metabolic pathways such as serum amino acid metabolism and pyrimidine metabolism in obese mice, and reshaped the composition and proportion of fecal gut microbiota in obese mice.<br><br>CONCLUSION: In summary, semaglutide could inhibit food intake and improve obesity, regulate serum metabolism and the composition of gut microbiota in mice. Bacterial transplantation is key to transmitting the improvement brought about by fecal microbiota transplantation of semaglutide to recipient mice.}, }
@article {pmid40550813, year = {2025}, author = {Song, B and Azad, MAK and Zhu, Q and Cheng, Y and Ding, S and Yao, K and Kong, X}, title = {Lactobacillus regulate muscle fiber type conversion in Chinese native pigs via tryptophan metabolism.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {114}, pmid = {40550813}, issn = {2055-5008}, support = {32350410424//National Natural Science Foundation of China/ ; 2022JJ30643//Hunan Province Natural Science Foundation/ ; 092GJHZ2022044FN//Future Partner Special Network Fund of Chinese Academy of Sciences/ ; 2023YFD1301305//National Key Research and Development Project/ ; }, mesh = {Animals ; *Tryptophan/metabolism ; Swine/microbiology ; *Lactobacillus/metabolism/physiology ; Mice ; Gastrointestinal Microbiome ; Kynurenic Acid/metabolism ; *Muscle Fibers, Slow-Twitch/metabolism ; Feces/microbiology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism/genetics ; AMP-Activated Protein Kinases/metabolism ; *Muscle Fibers, Skeletal/metabolism ; Metabolome ; }, abstract = {Identifying potential gut microbes and metabolites that can influence muscle fiber type is gaining interest in meat quality research. In this study, muscle fiber characteristics, muscle metabolite profiles, and gut microbiota and metabolome were compared among three pig breeds (Taoyuan black, TB; Xiangcun black, XB; and Duroc pigs). The results showed that the slow-twitch fiber percentage was higher (P < 0.05) in native pigs (TB and XB pigs) compared to Duroc pigs. The differences were mainly regulated by Lactobacillus abundance and tryptophan metabolism. Further, fecal microbiota transplantation from XB pigs transferred a higher slow-twitch fiber percentage, Lactobacillus abundance, kynurenic acid level, and AMPK/PGC-1α expression to mice. These findings suggest that Lactobacillus in the colon of TB and XB pigs, through kynurenic acid production, may promote slow-twitch fiber formation via the AMPK/PGC-1α signaling pathway.}, }
@article {pmid40550671, year = {2025}, author = {Zhang, S and Liu, X and Zhong, Y and Fu, Y}, title = {[Association between gut microbiota and hyperuricemia: insights into innovative therapeutic strategies].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {41}, number = {6}, pages = {2290-2309}, doi = {10.13345/j.cjb.250060}, pmid = {40550671}, issn = {1872-2075}, mesh = {*Hyperuricemia/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; Uric Acid/metabolism/blood ; Fecal Microbiota Transplantation ; Prebiotics ; Medicine, Chinese Traditional ; }, abstract = {Uric acid (UA) is the final metabolite of purines in the human body. An imbalance in UA production and excretion that disrupts homeostasis leads to elevated blood UA levels and the development of hyperuricemia (HUA). Approximately one-third of UA is excreted through the intestinal tract. As a crucial component of the intestinal microenvironment, the gut microbiota plays a pivotal role in regulating blood UA levels. Alterations or imbalances in gut microbiota composition are linked to the onset of HUA, which implies the potential of gut microbiota as a novel target for the prevention and treatment of HUA. This review introduces the occurrence mechanism and damage of hyperuricemia, examines the association between HUA and the gut microbiota and their metabolites, and explores the molecular mechanisms underlying gut microbiota-targeted therapies for HUA. Furthermore, it discusses the potential applications of probiotics, prebiotics, and traditional Chinese medicine (including both single herbs and compound formulas) with UA-lowering effects, along with cutting-edge technologies such as fecal microbiota transplantation and machine learning in HUA treatment. This review provides valuable perspectives and strategies for improving the prevention and treatment of HUA.}, }
@article {pmid40550654, year = {2025}, author = {Zhang, ZW and Ye, YJ and Shen, ZL}, title = {[Pathogenesis and progress in diagnosis and treatment of diversion colitis after colorectal cancer surgery].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {6}, pages = {627-632}, doi = {10.3760/cma.j.cn441530-20250326-00125}, pmid = {40550654}, issn = {1671-0274}, support = {82272841//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Colorectal Neoplasms/surgery ; *Colitis/diagnosis/therapy/etiology ; *Postoperative Complications/therapy/diagnosis/etiology ; Fecal Microbiota Transplantation ; }, abstract = {Diversion colitis (DC) is a non-specific inflammation caused by the lack of fecal flow stimulation in the distal intestine after intestinal diversion surgery. It is mainly related to factors such as intestinal flora imbalance, deficiency of short-chain fatty acid (SCFA) and immune abnormalities. The clinical manifestations of diversion colitis include abdominal pain, mucus and bloody stools, diarrhea and other symptoms, but most patients may have no obvious symptoms. Diagnosis mainly relies on endoscopic examination and pathological characteristics. Common endoscopic findings include mucosal congestion, edema, and increased fragility, and the histological manifestation is mainly lymphoid follicle hyperplasia. Other intestinal inflammatory diseases need to be excluded. The treatment options include surgical and conservative medical therapies, among which stoma reversal is the most effective treatment to restore intestinal continuity. Conservative treatments such as SCFA, 5-aminosalicylic acid (5-ASA), steroid or cellulose solution enema, leukocyte removal therapy and fecal microbiota transplantation (FMT) can be used for those who cannot undergo surgery, combined with diet and lifestyle support to improve symptoms. This article summarized the pathogenesis, status, clinical features, diagnostic strategy and treatment progress of DC, hoping to provide reference for the diagnosis and treatment of DC.}, }
@article {pmid40550557, year = {2025}, author = {Huang, CT and Wang, YC and Lin, SC and Lai, YC and Chen, SH and Feng, ST and Tsai, YJ}, title = {Impact of Gut Microbiota Alterations on Mitochondrial Bioenergetics in Cortical Astrocytes and Sensorimotor Impairment in a Rat Model of Lipopolysaccharide-Associated Encephalopathy.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000002637}, pmid = {40550557}, issn = {1540-0514}, abstract = {PURPOSE: Brain dysfunction is a significant complication of sepsis, commonly referred to as sepsis-associated encephalopathy (SAE). Alterations in gut microbiota during sepsis may contribute to development of SAE through the gut-brain axis. This study investigated effects of fecal transplantation from healthy or endotoxemic individuals on gut microbiota and brain function in a rat model of lipopolysaccharide (LPS)-associated encephalopathy.<br><br>METHODS: Following LPS induction, rats received daily oral gavage of fecal microbiota transplants for three days. Sensory and motor functions were assessed daily throughout the seven-day study period after LPS exposure. On day seven post-LPS, the study examined gut microbiota structure and composition, serum and fecal short-chain fatty acids (SCFAs) levels, ileal villus length, intestinal permeability, neuronal and glial ultrastructure, cytokine concentrations (pro-inflammatory and anti-inflammatory), and mitochondrial bioenergetics.<br><br>RESULTS: Administration of healthy donor feces preserved gut microbial structure and composition, maintained ileal villus length, and improved intestinal permeability following LPS treatment. Additionally, it increased SCFA levels, reduced pro-inflammatory cytokines, enhanced anti-inflammatory cytokine release, and restored sensitivity to mechanical and thermal stimuli, as well as motor function. Rats treated with healthy donor feces also exhibited reduced neuronal necrosis and a decreased density of mitochondria in cortical astrocytes. Notably, mitochondrial metabolism in LPS-treated rats returned to near-normal levels following treatment with healthy donor feces. In contrast, administration of endotoxemic donor feces exacerbated these effects in LPS-treated rats.<br><br>CONCLUSION: Ameliorating gut dysbiosis prevents mitochondrial dysfunction in astrocytes by promoting SCFA production and enhancing anti-inflammatory cytokine release. This process preserves neuronal integrity and mitigates the severity of encephalopathy.}, }
@article {pmid40550284, year = {2025}, author = {Biggs, GAY}, title = {Fecal microbiota transplant (FMT) is associated with the resolution of recurrent urinary tract infections (UTIs).}, journal = {Urology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urology.2025.06.040}, pmid = {40550284}, issn = {1527-9995}, }
@article {pmid40549339, year = {2025}, author = {Bulut, SD and Döndaş, HA and Celebioglu, HU and Sansano, JM and Döndaş, NY}, title = {Recent Insights About Probiotics Related Pharmabiotics in Pharmacology: Prevention and Management of Diseases.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {40549339}, issn = {1867-1314}, abstract = {The science of pharmacology investigates the effects of drugs on living organisms and vice versa. The frequency of side effects of some drugs used in traditional pharmacological treatment approaches and/or their inability to provide adequate treatment has led to the importance of new drug research and development (R&amp;D) studies. Recently, due to the discovery that some diseases are associated with an imbalanced microbiota (dysbiosis), there has been a surge of interest in therapeutic approaches that can restore balance (biosis) to the microbiota. This review discusses the current status of the pharmabiotic potential of probiotics, prebiotics, synbiotics, paraprobiotics, postbiotics, metabiotics, next-generation probiotics, and fecal microbiota transplantation; describes their pharmacological functions from gastrointestinal disorders to neurodegenerative diseases; and also discusses the developments in pharmaceutical applications of probiotics and their derivatives.}, }
@article {pmid40548224, year = {2025}, author = {Tüsüz Önata, E and Özdemir, &#xd6;}, title = {Fecal microbiota transplantation in allergic diseases.}, journal = {World journal of methodology}, volume = {15}, number = {2}, pages = {101430}, pmid = {40548224}, issn = {2222-0682}, abstract = {Microorganisms such as bacteria, fungi, viruses, parasites living in the human intestine constitute the human intestinal microbiota. Dysbiosis refers to compositional and quantitative changes that negatively affect healthy gut microbiota. In recent years, with the demonstration that many diseases are associated with dysbiosis, treatment strategies targeting the correction of dysbiosis in the treatment of these diseases have begun to be investigated. Faecal microbiota transplantation (FMT) is the process of transferring faeces from a healthy donor to another recipient in order to restore the gut microbiota and provide a therapeutic benefit. FMT studies have gained popularity after probiotic, prebiotic, symbiotic studies in the treatment of dysbiosis and related diseases. FMT has emerged as a potential new therapy in the treatment of allergic diseases as it is associated with the maintenance of intestinal microbiota and immunological balance (T helper 1/T helper 2 cells) and thus suppression of allergic responses. In this article, the definition, application, safety and use of FMT in allergic diseases will be discussed with current data.}, }
@article {pmid40548146, year = {2025}, author = {Vermeulen, A and Bootsma, E and Proost, S and Vieira-Silva, S and Kathagen, G and Vázquez-Castellanos, JF and Tito, RY and Sabino, J and Vermeire, S and Matthys, C and Raes, J and Falony, G}, title = {Dietary convergence induces individual responses in faecal microbiome composition.}, journal = {eGastroenterology}, volume = {3}, number = {2}, pages = {e100161}, pmid = {40548146}, issn = {2976-7296}, abstract = {BACKGROUND: Dietary variation has been identified as a key contributor to microbiome diversification. However, assessing its true impact in a cross-sectional setting is complicated by biological confounders and methodological hurdles. We aimed to estimate the impact of a reduction of dietary variation (dietary convergence) on faecal microbiota composition among individuals consuming a Western-type diet.<br><br>METHODS: 18 healthy volunteers recruited in the region of Flanders (Belgium) were followed up for 21 days. Participants were allowed to consume their habitual diet during a baseline and follow-up period (7 and 8&#x2009;days, respectively), intersected by a 6-day intervention during which dietary options were restricted to oat flakes, whole milk and still water. Faecal samples were collected on a daily basis. Quantitative microbiome profiles were constructed, combining 16S rRNA gene amplicon sequencing with flow cytometry cell counting. Blood samples were taken at the beginning and end of each study week.<br><br>RESULTS: While the intervention did not affect transit time (as assessed through the analysis of stool moisture), consumption of the restricted diet resulted in an increased prevalence of the Bacteroides2 microbiome community type. Microbial load and Faecalibacterium abundance decreased markedly. Despite dietary restrictions, no convergence of microbial communities (reduction of interindividual and intraindividual variation) was observed. The effect size (ES) of the intervention on genus-level microbiome community differentiation was estimated as 3.4%, but substantial interindividual variation was observed (1.67%-16.42%).<br><br>CONCLUSION: The impact of dietary variation on microbiome composition in a Western population is significant but limited in ES, with notable individual exceptions. Dietary convergence does not invariably translate into interindividual convergence of faecal microbial communities.}, }
@article {pmid40546666, year = {2025}, author = {Jeyaraman, N and Jeyaraman, M and Dhanpal, P and Ramasubramanian, S and Nallakumarasamy, A and Muthu, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Integrative review of the gut microbiome's role in pain management for orthopaedic conditions.}, journal = {World journal of experimental medicine}, volume = {15}, number = {2}, pages = {102969}, pmid = {40546666}, issn = {2220-315X}, abstract = {The gut microbiome, a complex ecosystem of microorganisms, has a significant role in modulating pain, particularly within orthopaedic conditions. Its impact on immune and neurological functions is underscored by the gut-brain axis, which influences inflammation, pain perception, and systemic immune responses. This integrative review examines current research on how gut dysbiosis is associated with various pain pathways, notably nociceptive and neuroinflammatory mechanisms linked to central sensitization. We highlight advancements in meta-omics technologies, such as metagenomics and metaproteomics, which deepen our understanding of microbiome-host interactions and their implications in pain. Recent studies emphasize that gut-derived short-chain fatty acids and microbial metabolites play roles in modulating neuroinflammation and nociception, contributing to pain management. Probiotics, prebiotics, synbiotics, and faecal microbiome transplants are explored as potential therapeutic strategies to alleviate pain through gut microbiome modulation, offering an adjunct or alternative to opioids. However, variability in individual microbiomes poses challenges to standardizing these treatments, necessitating further rigorous clinical trials. A multidisciplinary approach combining microbiology, immunology, neurology, and orthopaedics is essential to develop innovative, personalized pain management strategies rooted in gut health, with potential to transform orthopaedic pain care.}, }
@article {pmid40546462, year = {2025}, author = {Inayat, N and Zahir, A and Hashmat, AJ and Khan, A and Ahmad, A and Sikander, M and Zakir, S and Ahmad, S and Awan, SK and Raza, SS and Varrassi, G}, title = {Gut Microbiota as a Key Modulator of Chronic Disease: Implications for Diabetes, Autoimmunity, and Cancer.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e84687}, doi = {10.7759/cureus.84687}, pmid = {40546462}, issn = {2168-8184}, abstract = {The gut microbiota (GM) represents an intricate, dynamic, and complex ecosystem. It plays a key role in health and disease. The GM interacts with the host and modulates various physiological functions, including metabolism, immune regulation, and neurological function. This narrative review comprehensively analyses the role of the GM in the development and progression of three major chronic conditions, namely diabetes, autoimmune disorders, and cancer. Using a structured literature search strategy across databases such as Google Scholar, PubMed, Scopus, and Web of Science, relevant studies published between 2000 and 2025 were identified and analysed. This review highlights that dysbiosis contributes significantly to the pathogenesis of these chronic conditions. In type 2 diabetes mellitus (T2DM), alterations in the GM are associated with systemic inflammation, insulin resistance, and decreased microbial diversity. Similarly, in autoimmune disorders such as rheumatoid arthritis (RA), multiple sclerosis (MS), and inflammatory bowel disease (IBD), dysbiosis disrupts immune homeostasis, which in turn causes sustained inflammation and aberrant immune responses. Lastly, dysbiosis has been linked to the onset and progression of various gastrointestinal cancers through mechanisms including chronic inflammation and the production of carcinogenic metabolites. Fecal microbiota transplantation (FMT), probiotics, prebiotics, and dietary modifications are being explored for their potential to restore microbial balance and improve clinical outcomes. In conclusion, this review highlights the GM's pivotal role in the pathogenesis of chronic diseases and its potential as a therapeutic target.}, }
@article {pmid40546285, year = {2025}, author = {Pei, X and Liu, M and Yu, S}, title = {How is the human microbiome linked to kidney stones?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1602413}, doi = {10.3389/fcimb.2025.1602413}, pmid = {40546285}, issn = {2235-2988}, abstract = {In recent years, the incidence of kidney stones has continued to rise worldwide, and conventional treatments have limited efficacy in treating stones associated with recurrent or metabolic abnormalities. The microbiome, as the 'second genome' of the host, is involved in the development of kidney stones through metabolic regulation, immune homeostasis and inflammatory response. Studies have shown that the urinary microbiome of healthy people is dominated by commensal bacteria such as Lactobacillus and Streptococcus, which maintain microenvironmental homeostasis, whereas patients with renal stones have a significantly reduced diversity of intestinal and urinary microbiomes, with a reduced abundance of oxalic acid-degrading bacteria (e.g., Bifidobacterium oxalicum, Bifidobacterium bifidum), and a possible concentration of pathogenic bacteria (e.g., Proteus mirabilis). The microbiome regulates stone formation through mechanisms such as metabolites (e.g., short-chain fatty acids), changes in urine physicochemical properties (e.g., elevated pH), and imbalances in the inflammatory and immune microenvironments. For example, urease-producing bacteria promote magnesium ammonium phosphate stone formation through the breakdown of urea, whereas dysbiosis of the intestinal flora increases urinary oxalic acid excretion and exacerbates the risk of calcium oxalate stones. Microbiome-based diagnostic markers (e.g., elevated abundance of Aspergillus phylum) and targeted intervention strategies (e.g., probiotic supplementation, faecal bacteria transplantation) show potential for clinical application. However, technical bottlenecks (e.g., sequencing bias in low-biomass samples), mechanistic complexity (e.g., multistrain synergism), and individual heterogeneity remain major challenges for future research. Integration of multi-omics data, development of personalised therapies and interdisciplinary research will be the core directions to decipher the relationship between microbiome and kidney stones.}, }
@article {pmid40546239, year = {2025}, author = {Liang, J and Dong, X and Yang, J and Hu, N and Luo, X and Cong, S and Chen, J and Zhao, W and Liu, B}, title = {Buyang Huanwu Decoction Modulates the Gut Microbiota-C/EBPβ/AEP Axis to Ameliorate Cognitive Impairment in Alzheimer's Disease Mice.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {31}, number = {6}, pages = {e70480}, doi = {10.1111/cns.70480}, pmid = {40546239}, issn = {1755-5949}, support = {2024yjscx013//Innovative Research Project for Postgraduate Students of Heilongjiang University of Traditional Chinese Medicine/ ; LH2022H059//Natural Science Foundation of Heilongjiang Province of China/ ; LH2023H073//Natural Science Foundation of Heilongjiang Province of China/ ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and behavioral disturbances. Buyang Huanwu Decoction (BYHWD), a traditional Chinese herbal formulation, has demonstrated potential neuroprotective effects. This study aims to evaluate the therapeutic impact of BYHWD on cognitive impairments in 3×Tg mice and to investigate its underlying mechanism through modulation of the gut microbiota-C/EBPβ/AEP signaling pathway.<br><br>METHODS: In two independent experiments, we assessed the effects of BYHWD and its derived fecal microbiota transplantation (FMT-BYHWD) on behavioral performance, neuropathological alterations, and signaling pathways in 3&#xd7;Tg mice.<br><br>RESULTS: Treatment with BYHWD significantly improved cognitive function in 3&#xd7;Tg mice and mitigated AD-like pathological changes. By suppressing the C/EBP&#x3b2;/AEP signaling pathway, BYHWD reduced pathological A&#x3b2; plaque deposition, diminished tau hyperphosphorylation, and inhibited the release of pro-inflammatory cytokines. Further analysis revealed that BYHWD restored gut microbiota balance and suppressed the activation of the C/EBP&#x3b2;/AEP pathway in the hippocampus. Moreover, transplanting FMT-BYHWD from BYHWD-treated mice to germ-free 3&#xd7;Tg mice also ameliorated their cognitive deficits and AD-like pathology, suggesting that the anti-AD effects of BYHWD are mediated through the gut-brain axis by regulating the interplay between gut microbiota and the C/EBP&#x3b2;/AEP signaling pathway.<br><br>CONCLUSION: This study uncovers the mechanism by which BYHWD improves cognitive deficits and neuropathological changes in 3&#xd7;Tg mice via the gut-brain axis, mediated by the modulation of the gut microbiota-C/EBP&#x3b2;/AEP signaling pathway, providing a novel therapeutic strategy for AD.}, }
@article {pmid40544256, year = {2025}, author = {Mannavola, CM and De Maio, F and Marra, J and Fiori, B and Santarelli, G and Posteraro, B and Sica, S and D'Inzeo, T and Sanguinetti, M}, title = {Bloodstream infection by Lactobacillus rhamnosus in a haematology patient: why metagenomics can make the difference.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {47}, pmid = {40544256}, issn = {1757-4749}, support = {PE00000007, INF-ACT//EU funding for the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases/ ; }, abstract = {BACKGROUND: Bloodstream infections (BSIs) pose a persistent threat to hospitalized patients, particularly those who are immunocompromised and susceptible to infections caused by anaerobic or facultative anaerobic bacteria. Alterations in gut microbiota composition can predispose individuals to intestinal domination by one or more pathobionts, increasing the risk of bacterial translocation into the bloodstream and subsequent bacteremia.<br><br>CASE PRESENTATION: We report the case of a 20-year-old female with multiple relapsed/refractory Philadelphia-negative B-cell acute lymphoblastic leukemia, initially referred to our hematology center for CAR-T cell therapy. The patient ultimately underwent allogeneic hematopoietic stem cell transplantation, which was complicated by infections, moderate-to-severe graft-versus-host disease, hepatic sinusoidal obstruction syndrome, and transplant-associated thrombotic microangiopathy, all contributing to a fatal outcome. Blood cultures obtained in the final week before the patient succumbed to multi-organ toxicity grew Lactobacillus rhamnosus. A fecal sample collected concurrently for intestinal microbiota characterization revealed a marked predominance of Bacillota (98.5%), with Lacticaseibacillus dominating at 47.9%, followed by Pediococcus (18.59%) and Staphylococcus (3.5%) at the genus level. We performed genomic comparison between the L. rhamnosus isolated from blood cultures and the best-matched strain detected in the intestinal microbiota.<br><br>CONCLUSIONS: We report the isolation of L. rhamnosus from blood cultures in a patient post hematopoietic cell transplantation, with genomic similarity to a gut-dominant L. rhamnosus strain. This case highlights the potential link between intestinal domination and subsequent bloodstream infection, supporting the value of gut microbiota profiling as an adjunctive tool for monitoring high-risk patients, such as hematopoietic cell transplant recipients.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13099-025-00722-3.}, }
@article {pmid40544212, year = {2025}, author = {Lv, J and Hao, P and Zhou, Y and Liu, T and Wang, L and Song, C and Wang, Z and Liu, Z and Liu, Y}, title = {Role of the intestinal flora-immunity axis in the pathogenesis of rheumatoid arthritis-mechanisms regulating short-chain fatty acids and Th17/Treg homeostasis.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {617}, pmid = {40544212}, issn = {1573-4978}, support = {2024ZKZ009//Southwest Medical University (SWMU) School-level Scientific Research Program/ ; }, abstract = {BACKGROUND: The pathogenesis of rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is closely linked to the interactions between intestinal flora and metabolites. Recent research has shown that the "gut-joint axis" is an important regulator of immune homeostasis, gut microbiota dysbiosis not only causes pro-inflammatory bacteria to proliferate abnormally, but it also decreases the biosynthesis of short-chain fatty acids (SCFAs). This dual imbalance ultimately exacerbates synovial inflammation and encourages bone destruction by upsetting the balance of Th17/Treg cells, that is, the over-activation of Th17 cells and the impaired function of regulatory T cells (Treg).<br><br>OBJECTIVE: To clarify the molecular mechanism by which intestinal flora-derived SCFAs alter the pathogenic process of RA by controlling Th17/Treg balance, and to establish a theoretical foundation for targeted treatments.<br><br>METHODS: We integrated multidisciplinary evidence to create a "flora-SCFAs-immunity-joints" by conducting a systematic search of domestic and international literature in PubMed, Web of Science, and other databases over the past ten years, with a focus on intestinal flora composition, SCFA biosynthesis, Th17/Treg immunoregulation, and RA animal model research. We create a "flora-SCFAs-immunity-joint" network by integrating information from many disciplines.<br><br>OUTCOMES: Dietary fiber is broken down by intestinal flora to produce SCFAs (acetic, propionic, and butyric acids), which control Th17/Treg balance in two ways: (1) Encourage Treg differentiation: propionic acid activates the GPR43-cAMP/PKA-CREB pathway, which promotes Treg expansion and secretion of IL-10/TGF-&#x3b2;; (2) Inhibit Th17 polarization, SCFAs inhibited Th17 cell differentiation, down-regulated IL-23 secretion from dendritic cells, and blocked IL-6/STAT3 and ROR&#x3b3;t signaling. Butyric acid also inhibits histone deacetylase (HDAC) activity, Foxp3 expression, and epigenetic stability. In a collagen-induced arthritis (CIA) paradigm, animal studies shown that fecal transplantation or SCFA supplementation dramatically decreased bone degradation and joint inflammatory scores. Its therapeutic translational potential was suggested by the negative correlation found between the Th17/Treg ratio and the amount of SCFAs in the gut of RA patients.<br><br>CONCLUSION: Through multi-target control of Th17/Treg balance, SCFAs show distinct benefits over conventional immunosuppression in the treatment of RA. Verification is still required for the pharmacokinetic constraints of SCFAs, variations in individual flora, and causative processes. To support the specific immune intervention in RA, it will be important in the future to integrate multi-omics technology to evaluate the trans-organ regulatory network of the "gut-joint axis" and to create nano-delivery methods or modified bacterial tactics to increase the targeting of SCFAs.}, }
@article {pmid40542451, year = {2025}, author = {Ji, S and Ahmad, F and Peng, B and Yang, Y and Su, M and Zhao, X and Vatanen, T}, title = {Engrafting gut bacteriophages have potential to modulate microbial metabolism in fecal microbiota transplantation.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {149}, pmid = {40542451}, issn = {2049-2618}, support = {U22A20365//Joint Funds of National Natural Science Foundation of China/ ; T2341019//National Natural Science Foundation of China/ ; 2023A1515012429//Natural Science Foundation of Guangdong Province/ ; 2024B03J1343//Guangzhou Science and Technology Plan Project/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is widely used to treat severe infections and investigated for the treatment of complex diseases. The therapeutic efficacy of FMT is related to the successful engraftment of bacteriophages from healthy donors to recipients. However, gut bacteriophage contributions to FMT engraftment and treatment outcomes remain unclear.<br><br>METHODS: The gut phageome from previously published metagenomes of donors and recipients across 23 FMT studies was assembled and functionally annotated for a meta-analysis.<br><br>RESULTS: Gut phageome profiles of FMT recipients, especially those with recurrent Clostridioides difficile infection (rCDI), shifted toward donor phageomes, accompanied by increased phageome alpha diversity. Engraftment of donor phages varied between recipient conditions with the highest engraftment rate, overrepresented by putative temperate phage, in patients with rCDI. Consistently, a higher proportion of auxiliary metabolic genes (AMGs), with the potential to support and modulate bacterial metabolism, were annotated on putative temperate phages.<br><br>CONCLUSIONS: FMT leads to significant taxonomic, functional, and lifestyle shifts in recipient phageome composition. Future FMT studies should include gut phageome characterization and consider it as a potential factor in microbial community shifts and treatment outcomes. Video Abstract.}, }
@article {pmid40540980, year = {2025}, author = {Noviello, D and Amoroso, C and Vecchi, M and Facciotti, F and Caprioli, F}, title = {Curing inflammatory bowel diseases: breaking the barriers of current therapies- emerging strategies for a definitive treatment.}, journal = {Current opinion in immunology}, volume = {95}, number = {}, pages = {102593}, doi = {10.1016/j.coi.2025.102593}, pmid = {40540980}, issn = {1879-0372}, abstract = {Chronic intestinal inflammation in inflammatory bowel diseases (IBD) reflects the interplay of genetic predisposition, immune dysregulation, microbial imbalance, and epithelial barrier defects. Current therapies for IBD primarily focus on controlling inflammation necessitating lifelong treatment and face a 'therapeutic ceiling' due to primary and secondary loss of efficacy over time. Immune-mediated approaches do not address additional pathogenic mechanisms, such as impairment of epithelial barrier and gut microbial ecology. Thus, innovative strategies are required to foster the field closer to a definitive cure. This review discusses novel strategies to overcome current therapeutic limitations, including immune reset via hematopoietic stem cell transplantation and B cell-targeted therapies, antigen-specific interventions such as chimeric antigen receptor T cells and tolerogenic vaccines, and intestinal epithelial barrier restoration. We also explore microbiota-based strategies - ranging from fecal microbiota transplantation to engineered consortia and bacteriophages - and discuss the adjunctive role of diet. Together, we outline a potential research roadmap toward a potential cure for IBD.}, }
@article {pmid40538711, year = {2025}, author = {Lathakumari, RH and Vajravelu, LK and Gopinathan, A and Vimala, PB and Panneerselvam, V and Ravi, SSS and Thulukanam, J}, title = {The gut virome and human health: From diversity to personalized medicine.}, journal = {Engineering microbiology}, volume = {5}, number = {1}, pages = {100191}, pmid = {40538711}, issn = {2667-3703}, abstract = {The human gut virome plays a crucial role in the gut and overall health; its diversity and regulatory functions influence bacterial populations, metabolism, and immune responses. Bacteriophages (phages) and eukaryotic viruses within the gut microbiome contribute to these processes, and recent advancements in sequencing technologies and bioinformatics have greatly expanded our understanding of the gut virome. These advances have led to the development of phage-based therapeutics, diagnostics, and artificial intelligence-driven precision medicine. The emerging field of phageomics shows promise for delivering personalized phage therapies that combat antimicrobial resistance by specifically targeting pathogenic bacteria while preserving beneficial microbes. Moreover, CRISPR-Cas systems delivered via phages have shown success in selectively targeting antibiotic resistance genes and enhancing treatment effectiveness. Phage-based diagnostics are highly sensitive in detecting bacterial pathogens, offering significant benefits for human health and zoonotic disease surveillance. This synthesis of the current knowledge highlights the pivotal role of the gut virome in regulating microbial communities and its transformative potential in personalized medicine, emphasizing its importance in advancing therapeutic and diagnostic strategies for improving health outcomes.}, }
@article {pmid40535532, year = {2025}, author = {Wang, Q and Xu, G and Yan, O and Wang, S and Wang, X}, title = {Radiation-induced injury and the gut microbiota: insights from a microbial perspective.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251347347}, pmid = {40535532}, issn = {1756-283X}, abstract = {Although radiotherapy is the second most effective cancer treatment, radiation injuries limit its use. About 80% of abdominal-pelvic radiotherapy patients develop acute radiation enteritis, with 20% discontinuing radiotherapy. The lack of effective mitigation measures restricts its clinical application. Recent studies have proposed gut microbiota as a potential biomarker for radiation injuries. However, the interaction between gut microbiota and radiation injuries remains poorly understood. This review summarizes two forms of interaction between gut microbiota and radiation injuries based on the location of the radiation field. One type of interaction, referred to as "direct interaction," involves changes in the diversity and composition of gut microbiota, alterations in microbiota-derived metabolites, disruption of the intestinal barrier, activation of inflammatory responses within the intestine, and involvement of the host's immune system. The second form, called "indirect interaction," includes the influence of the gut microbiota on various body systems, such as gut microbiota-brain axis, gut microbiota-cardiopulmonary axis, and gut microbiota-oral axis. Additionally, we examine promising interventions aimed at reshaping the gut microbiota, including the use of probiotics, prebiotics, and fecal microbiota transplantation. The interaction between radiation injuries and gut microbiota is more complex than previously understood. Therefore, further clarification of the underlying mechanisms will facilitate the application of gut microbiota in preventing and alleviating radiation injuries.}, }
@article {pmid40535011, year = {2025}, author = {Wu, N and Ning, K and Liu, Y and Wang, Q and Li, N and Zhang, L}, title = {Relationship between high-fat diet, gut microbiota, and precocious puberty: mechanisms and implications.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1564902}, pmid = {40535011}, issn = {1664-302X}, abstract = {Precocious puberty (PP) is the second most common pediatric endocrine disorder globally and poses a growing public health concern, particularly among girls. While the exact biological mechanisms underlying PP remain unclear, unhealthy dietary patterns, particularly the consumption of a high-fat diet (HFD), are recognized as significant modifiable risk factors. The gut microbiota (GM) is an environmental factor that is disrupted by HFD and may modulate the onset and progression of PP. This review explored the intricate relationship between HFD, GM, and PP, and elucidated the potential mechanisms by which HFD may promote PP development by summarizing evidence from preclinical to clinical research, focusing on the role of GM and its derived metabolites, including short-chain fatty acids, bile acids, lipopolysaccharides, and neurotransmitters. Mechanistic exploration provides novel insights for developing microbiota-targeted therapeutic strategies, such as dietary and lifestyle interventions, fecal microbiota transplantation, probiotics, and traditional Chinese medicine, paving the way for promising approaches to prevent and manage PP.}, }
@article {pmid40534699, year = {2025}, author = {Yu, JX and Wu, J and Chen, X and Zang, SG and Li, XB and Wu, LP and Xuan, SH}, title = {Gut microbiota in liver diseases: initiation, development and therapy.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1615839}, pmid = {40534699}, issn = {2296-858X}, abstract = {The gut microbiota plays a pivotal role in the pathogenesis and progression of various liver diseases, including viral hepatitis, alcoholic fatty liver disease, metabolic dysfunction-associated steatotic liver disease, drug-induced hepatitis, liver cirrhosis, hepatocellular carcinoma, and other hepatic disorders. Research indicates that dysbiosis of the gut microbiota can disrupt the integrity of the intestinal barrier and interfere with the immune functions of the gut-liver axis, thereby mediating the progression of liver diseases. Analysis of microbial composition and metabolites in fecal samples can assess the diversity of gut microbiota and the abundance of specific microbial populations, providing auxiliary diagnostic information for liver diseases. Furthermore, interventions such as fecal microbiota transplantation, probiotics, prebiotics, bacteriophages, and necessary antibiotic treatments offer multiple approaches to modulate the gut microbiota, presenting promising new strategies for the prevention and treatment of liver diseases. This review summarizes the latest research advances on the role of gut microbiota in liver diseases, offering novel theoretical foundations and practical directions for the diagnosis and treatment of hepatic disorders.}, }
@article {pmid40533850, year = {2025}, author = {Ye, Q and Hu, Y and Jiang, H and Luo, T and Han, L and Chen, Y and Chen, J and Ma, L and He, Z and Yan, X}, title = {Maternal intestinal L. vaginalis facilitates embryo implantation and survival through enhancing uterine receptivity in sows.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {145}, pmid = {40533850}, issn = {2049-2618}, support = {32202700//National Natural Science Foundation of China/ ; 31925037//National Natural Science Foundation of China/ ; 2022YFD1300405//National Key Research and Development Program of China/ ; 2022YFD1300405//National Key Research and Development Program of China/ ; 2022YFD1300405//National Key Research and Development Program of China/ ; 2022020801020232//Knowledge Innovation Program of Wuhan-Shuguang Project/ ; AML2023B06//National Key Laboratory of Agricultural Microbiology/ ; 2662023DKPY002//Fundamental Research Funds for the Central University/ ; }, mesh = {Animals ; Female ; *Embryo Implantation/physiology ; Swine ; *Gastrointestinal Microbiome/physiology ; Pregnancy ; Mice ; *Uterus/physiology ; RNA, Ribosomal, 16S/genetics ; Litter Size ; Metabolomics ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: The embryo implantation quality during early pregnancy is the predominant factor for embryo survival and litter performance in sows. Gut microbiota is demonstrated to show a correlation to pregnancy outcomes by participating in regulating maternal metabolism. However, the specific functional microbiota and its mechanical effects on regulating embryo implantation and survival remain unclear. The objective of this study was to clarify whether embryo implantation and litter performance were affected by maternal intestinal microbiota, and to identify specific microbial communities and its mechanism in regulating embryo implantation.<br><br>RESULTS: In this study, we first conducted 16S rRNA sequencing and metabolomic analysis revealing the intestinal microbiota and metabolism of 42 sows with different litter size to select the potential functional microbiota that may contribute to embryo survival. Then, we explored the effects of that microbiota on embryo implantation and litter performance through microbiota transplantation in mice and sows. We found that maternal intestinal L. vaginalis exhibits enrichment in sows with higher litter size, which could facilitate embryo implantation and survival and ultimately increases litter size in mice. We further employed transcriptomic analysis to determine the characteristics of uterus, which found an enhanced uterine receptivity after L. vaginalis gavage. The plasma untargeted metabolomic analysis after L. vaginalis gavage in mice and targeted metabolomics analysis of in vitro cultured medium of L. vaginalis were used to evaluate the metabolic regulation of L. vaginalis and to reveal the underlying functional metabolites. Next, an increasing adhesion rate of endometrial-embryonic cells and an obvious increasing formation of pinopodes in cell surface of porcine endometrial epithelial cells were observed after treatments of L. vaginalis metabolites, especially galangin and daidzein. Also, the gene expression levels related to uterine receptivity were increased after treatments of L. vaginalis metabolites in porcine endometrial epithelial cells. Finally, we found that L. vaginalis or its metabolites supplementation during early gestation significantly increased the litter performance in sows.<br><br>CONCLUSIONS: Overall, intestinal microbial-host interactions can occur during early pregnancy and may be contribute to maternal metabolic changes and influence pregnancy outcomes in mammals. Our study provides insights of maternal intestinal L. vaginalis to enhance uterine receptivity and to benefit embryo/fetal survival through a gut-uterus axis, contributing to advanced concept and novel strategy to manipulate gut microbiota during early pregnancy, and in turn to improve embryo implantation and reduce embryo loss in sows. Video Abstract.}, }
@article {pmid40532535, year = {2025}, author = {Wang, Z and He, Y and Luo, M and Liu, S and Hou, J and Cao, B and An, X}, title = {Transfer toxicity of polystyrene microplastics in vivo: Multi-organ crosstalk.}, journal = {Environment international}, volume = {202}, number = {}, pages = {109604}, doi = {10.1016/j.envint.2025.109604}, pmid = {40532535}, issn = {1873-6750}, abstract = {The accumulation of microplastics (MPs) within the environment caused serious ecological and health problems. Nevertheless, its systemic toxicity to organisms and its mechanisms lack effective evidence. This study established a model of MP exposure through the gavage of polystyrene (PS)-MPs particles to maternal mice on days 1 to 21 of lactation. The results demonstrated that PS-MPs were distributed widely in maternal mice, occurring mainly in the feces, colon, liver and mammary glands. Further experiments revealed that the gut and blood-milk barriers were disrupted, and pathological injury and inflammatory reactions were observed in the liver, gut, and mammary glands. Metabolomic and metagenome analysis indicated abnormalities in hepatic bile acid metabolism and significant alterations in the gut microbiota after exposure to PS-MPs. These alterations led to increased disruption of the intestine-liver axis. Notably, with fecal microbiota transplantation and antibiotic experiments, we observed that elimination of the intestinal microbiota reduced tissue inflammation and improved gut and blood-milk barrier leakage. These findings demonstrated that PS-MPs exaggerated intestine-liver axis disorders by inducing colonic injury, intestinal ecological dysregulation and abnormal hepatic bile acid metabolism. Furthermore, PS-MPs translocated via the intestine-liver axis and exerted broader toxic effects on mammary tissue. Overall, our study uncovered the transfer toxicity of PS-MPs in mice, proposing the possibility of a gut-liver-mammary axis.}, }
@article {pmid40532322, year = {2025}, author = {Zhao, Y and Gong, N and Wang, S and Yuan, Q and Chen, X and Li, B and Zhang, L and Li, W and Zhu, R and Zhang, J and Zhang, W}, title = {Dynamic changes in intestinal microbiota mediate mechanical hyperalgesia in surgical menopause model: a potential mechanism of DRG neuroinflammation.}, journal = {International immunopharmacology}, volume = {161}, number = {}, pages = {115098}, doi = {10.1016/j.intimp.2025.115098}, pmid = {40532322}, issn = {1878-1705}, abstract = {The role of the intestinal microbiota in hyperalgesia in ovariectomized mice remains unclear. This study aimed to investigate pain behavior and dynamic changes in the intestinal microbiota and the levels of related metabolites in a model of surgical menopause and to verify the hypothesis that the intestinal microbiota mediates the occurrence and persistence of hyperalgesia through neuroinflammation. An ovariectomy (OVX) model was constructed to assess the intestinal microbiota composition, the levels of related metabolites, and inflammation levels in the spinal dorsal root ganglion (DRG). Fecal microbiota transplantation (FMT) was used to alter the intestinal microbiota, and its impact on pain-related behaviors and the level of inflammation in the DRG was evaluated. The mechanical pain threshold was significantly lower in the OVX group compared with the sham group at 4-8 w after surgery, and the thermal pain threshold was greater at 5 and 8 w after surgery. A decrease in the mechanical pain threshold was observed in the OVX group 5, and 7-9 weeks after FMT, indicating hyperalgesia. PCoA and OPLS-DA revealed differences in the composition of the microbiota and the abundance of related metabolites between the OVX and sham groups. Correlation analysis revealed an association between pain thresholds and the levels and metabolites of certain bacterial genera. The expression of C/EBPβ and IL-1β in the OVX group was greater than that in the sham group, and the expression of IL-6, IL-1β, and TRPV1 in the sham group was greater than that in the OVX group after FMT. In conclusion, the dynamic changes in the intestinal microbiota in female mice induced by surgical menopause result in hyperalgesia, possibly due to an increase in the severity of inflammation in the spinal DRG.}, }
@article {pmid40531376, year = {2025}, author = {Wu, Y and Wong, OWH and Chen, S and Ng, SC and Su, Q and Chan, FKL}, title = {Gastrointestinal health and nutritional strategies in autism spectrum disorder.}, journal = {Journal of gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {40531376}, issn = {1435-5922}, support = {R4030-22//Research Grants Council-Research Impact Fund/ ; NCI202346//New Cornerstone Science Foundation/ ; PF22-77807//Hong Kong PhD Fellowship Scheme (HKPFS) of the Research Grants Council of Hong Kong/ ; }, abstract = {Beyond the hallmark social and sensory difficulties in autism spectrum disorder (ASD), the comorbid gastrointestinal (GI) conditions and their potential link to the severity of core symptoms require clinical attention. Although evidence indicates that autistic children face a greater risk of GI disorders and require more intensive nutritional management compared to neurotypical peers, standard guidelines for managing GI symptoms in this population remain lacking. This review seeks to pinpoint critical considerations for the implementation of nutrition-based strategies aimed at addressing GI dysfunction in individuals with ASD. By emphasizing clinical translation and the mechanistic understanding of these strategies, it highlights the importance of restoring gut homeostasis as a pathway to improve functional independence and overall well-being. Furthermore, we outline priorities for clinical research aimed at developing evidence-based nutritional recommendations to support GI health in autistic individuals, emphasizing personalized and population-specific needs.}, }
@article {pmid40530459, year = {2025}, author = {Kabage, AJ and Haselhorst, PJ and Khoruts, A}, title = {Donor-centric administration of the stool donor program is vital to its feasibility and patient safety.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2508950}, doi = {10.1080/19490976.2025.2508950}, pmid = {40530459}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/ethics/adverse effects/standards ; *Clostridium Infections/therapy ; *Patient Safety ; *Feces/microbiology ; *Tissue Donors ; Gastrointestinal Microbiome ; Clostridioides difficile ; }, abstract = {Human stool-based products composed of fecal microbiota are a new frontier of medical therapeutics development. The development of standardized manufacturing protocols of donor microbiota has transformed fecal microbiota transplantation (FMT) from a crude and rarely used procedure to a widely accepted and highly effective option for treatment Clostridioides difficile infections. There is also a growing interest in using microbiota transplant therapies for multiple other clinical indications. In this manuscript, we review the logistical challenges experienced by various stool banks and our own group in establishing and administering a stool donor program. Furthermore, we explore and highlight the multiple ethical considerations that are ultimately essential to product safety and efficacy and propose basic principles that are necessary to maintain stool donor program integrity.}, }
@article {pmid40529581, year = {2025}, author = {Xu, D and Lu, Z and Li, Q and Cheng, Y and Yang, Z}, title = {Decoding the gut-sleep Nexus: a bibliometric mapping of gut microbiota and sleep disorders.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1598173}, pmid = {40529581}, issn = {1664-302X}, abstract = {BACKGROUND: An increasing number of studies have focused on the interaction between gut microbiota and sleep disorders. However, there is currently no bibliometric analysis of the literature on gut microbiota and sleep disorders. This study employs bibliometric methods to analyze the current research status and hotspots in the field of gut microbiota and sleep disorders, providing a reference for future research in this area.<br><br>METHODS: Articles related to gut microbiota and sleep disorders were retrieved from the WOS core database, covering the period from the database's inception to December 31, 2024. After rigorous screening, VOSviewer and CiteSpace were used to conduct analyses on quantity, collaboration networks, clustering, and citation bursts.<br><br>RESULTS: The number of articles on gut microbiota and sleep disorders has increased annually, with a significant surge after 2022. China has the highest number of publications, while the United States has the highest citation count. The institution with the most publications is Shanghai Jiao Tong University, and the institution with the most citations is Deakin University. The top 10 journals by publication volume are all ranked above Q2 in the JCR. The most cited article is "Gut microbiome diversity is associated with sleep physiology in humans" by Smith et al., published in PLOS ONE in 2019. The top 10 most frequent keywords are gut microbiota, sleep, depression, inflammation, chain fatty acids, anxiety, brain, oxidative stress, obesity, and health. The keyword cluster "obstructive sleep apnea" is a focal research direction, while fecal microbiota transplantation is a current research hotspot.<br><br>CONCLUSION: This study reveals the publication trends, collaboration relationships among countries, regions, and authors, and recent research hotspots in the field of gut microbiota and sleep disorders through bibliometric methods, providing an objective data reference for scientific research in this domain.}, }
@article {pmid40529577, year = {2025}, author = {Wu, S and Chen, N and Wang, C and So, KF}, title = {Research focus and trends of the association between gut microbiota and neuroinflammation.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1564717}, pmid = {40529577}, issn = {1664-302X}, abstract = {BACKGROUND: The interaction between the gut microbiota and neuroinflammation plays a crucial role in the pathogenesis of many diseases, particularly neurodegenerative diseases, and has become one of the focal points of research in recent years. Despite the large number of related studies, there is currently a lack of comprehensive analysis and prediction of these data to drive the field forward. This study aims to systematically analyze the clinical practices and research hotspots of the underlying mechanisms in this field using bibliometric and visualization methods, and to explore the future development pathways.<br><br>METHODS: CiteSpace, VOSviewer, GraphPad Prism and other software were used to analyze 1,404 studies on gut microbiota and neuroinflammation collected by the core of the Web of Science since 2000, to visually present the collaborative network between literatures, structure of authors and countries, co-occurrence of keywords, emerging reference literature, and research hotspots.<br><br>RESULTS: From 2000 to 2024, the number of related papers on this topic showed an overall upward trend, and the annual citation peaked in 2020, with significant contributions from China and the United States. Research focused on the relationship between gut microbiota and neuroinflammation, with a particular emphasis on investigating the mechanisms of the microbiota-gut-brain axis through both basic and clinical research. Treatment strategies include probiotic therapy, fecal microbiota transplantation and traditional Chinese medicine.<br><br>CONCLUSION: This study comprehensively reviews the research progress on the association between gut microbiota and neuroinflammation, and discusses the current research focus and frontier directions of this relationship, so as to provide reference for the development of this field.}, }
@article {pmid40529304, year = {2025}, author = {Chen, Z and Jin, D and Hu, J and Guan, D and Bai, Q and Gou, Y}, title = {Microbiota and gastric cancer: from molecular mechanisms to therapeutic strategies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1563061}, pmid = {40529304}, issn = {2235-2988}, mesh = {*Stomach Neoplasms/therapy/microbiology/pathology ; Humans ; *Gastrointestinal Microbiome ; Dysbiosis/complications/microbiology ; Tumor Microenvironment ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Gastric cancer, a prevalent malignancy globally, is influenced by various factors. The imbalance in the gut microbiome and the existence of particular intratumoural microbiota could have a strong connection with the onset and progression of gastric cancer. High-throughput sequencing technology and bioinformatics analysis have revealed a close correlation between abnormal abundance of specific microbial communities and the risk of gastric cancer. These microbial communities contribute to gastric cancer progression through mechanisms including increasing cellular genomic damage, inhibiting DNA repair, activating abnormal signaling pathways, exacerbating tumor hypoxia, and shaping a tumor immune-suppressive microenvironment. This significantly impacts the efficacy of gastric cancer treatments, including chemotherapy and immunotherapy. Probiotic, prebiotic, antibiotic, carrier-based, dietary interventions, fecal microbiota transplantation, and traditional Chinese medicine show potential applications in gastric cancer treatment. However, the molecular mechanisms regarding dysbiosis of microbiota, including gut microbiota, and intra-tumoral microbiota during the progression of gastric cancer, as well as the therapeutic efficacy of microbiota-related applications, still require extensive exploration through experiments.}, }
@article {pmid40528217, year = {2025}, author = {Ruszkowski, J and Kachlik, Z and Walaszek, M and Storman, D and Podkowa, K and Garbarczuk, P and Jemioło, P and Łyzińska, W and Nowakowska, K and Grych, K and Dębska-Ślizień, AM}, title = {Fecal microbiota transplantation from patients into animals to establish human microbiota-associated animal models: a scoping review.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {662}, pmid = {40528217}, issn = {1479-5876}, support = {"Medical University of Gdansk Excellence Initiative- Research University" program//Gda&#x144;ski Uniwersytet Medyczny/ ; }, mesh = {Animals ; Humans ; Mice ; *Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) from humans with specific medical conditions to animal models can demonstrate causality by inducing or exacerbating pathophenotypes, linking the gut microbiota to health outcomes.<br><br>METHODS: We conducted a scoping review searching MEDLINE, EMBASE, Scopus, and Web of Science through July 2024 to identify human noninfectious diseases studied using FMT in animal models, investigate FMT methodologies, and assess the feasibility of systematic reviews on the role of the microbiota in specific diseases.<br><br>RESULTS: From 605 reports of 489 studies, we found that inflammatory bowel diseases, irritable bowel syndrome, obesity, colorectal cancer, and depression were the most commonly studied, with cancer research focusing on immunotherapy non-responsiveness. In a random sample of studies, gastrointestinal outcomes were most frequently reported, with remarkably high rates (>&#x2009;80%) of successful induction of disease-specific alterations for intestinal barrier function, gastrointestinal inflammation, circulating immune parameters, and fecal metabolites. Most studies used C57BL/6 mice and oral gavage administration, with recipients being either germ-free or antibiotic-pretreated. We created tables linking conditions with publications to facilitate future systematic reviews.<br><br>CONCLUSIONS: Although human-to-animal FMT studies cover diverse conditions, methodological heterogeneity and inconsistent reporting hinder comparability. Standardized protocols and guidelines are needed. For several conditions, sufficient literature exists to assess the role of the gut microbiota in human health through systematic reviews.}, }
@article {pmid40528179, year = {2025}, author = {Chen, K and Wang, H and Yang, Y and Tang, C and Sun, X and Zhou, J and Liu, S and Li, Q and Zhao, L and Gao, Z}, title = {Common mechanisms of Gut microbe-based strategies for the treatment of intestine-related diseases: based on multi-target interactions with the intestinal barrier.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {288}, pmid = {40528179}, issn = {1478-811X}, support = {82274343//National Natural Science Foundation of China/ ; 82405302//National Natural Science Foundation of China/ ; ZR2024QH032//Shandong Provincial Natural Science Foundation/ ; 24-4-4-zrjj-111-jch//Qingdao Natural Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; *Intestinal Mucosa/microbiology/metabolism ; Probiotics/therapeutic use ; *Intestinal Diseases/microbiology/therapy ; Fecal Microbiota Transplantation ; }, abstract = {The concurrent occurrence and exacerbation of multiple diseases, including geriatric diseases and chronic diseases, impose a heavy burden on human health and medical expenses. Clarifying the common mechanisms of related multifarious diseases and developing preventive and therapeutic strategies with synergistic effects for multiple diseases are of great significance in alleviating the burden on the medical system and reducing patients' burden of drug metabolism. Recent studies have revealed that gut microbiota disorders and intestinal barrier damage, which consequently cause metabolic and immunological disorders, may be a common pathological basis underlying various intestinal-related diseases. In this review, we focus on the intestinal barrier function, summarizing the multi-target interactions and common mechanisms involved in diseases related to the gut such as ulcerative colitis, colorectal cancer, and type 2 diabetes. We identified gut microbe-based strategies, including probiotics, prebiotics, synbiotics, postbiotics, as well as potential targets in faecal microbiota transplant and berberine. The common mechanisms and key targets in the treatment of these diseases mainly include increasing the abundance of beneficial genera Bifidobacterium and Lactobacillus, increasing the levels of Short Chain Fatty Acids, restoring the intestinal mechanical barrier, and suppressing gut inflammation infiltration. We aim to provide a crucial basis and direction for the development of novel drugs with therapeutic effects for multiple diseases, thereby alleviating the patients' burden of medication and enhancing the efficacy of treatment.}, }
@article {pmid40527176, year = {2025}, author = {Wang, Z and Wang, Y and Zhang, J and Yin, K and Luo, H and Huang, W}, title = {Multi-omics approaches to explore the therapeutic mechanism for ginsenoside Rg1 against MASLD.}, journal = {Biochemical and biophysical research communications}, volume = {776}, number = {}, pages = {152161}, doi = {10.1016/j.bbrc.2025.152161}, pmid = {40527176}, issn = {1090-2104}, abstract = {Ginsenoside Rg1 (G-Rg1), a traditional Chinese medicine, alleviates metabolic dysfunction-associated steatotic liver disease (MASLD). However, the mechanism by which G-Rg1 improves metabolic disorders in MASLD by regulating the gut microbiota remains ambiguous‌. We constructed a diet-induced murine MASLD model and employed 16S rRNA sequencing and non-targeted metabolomic analysis to ‌investigate the mechanism of G-Rg1 in treating MASLD, focusing on its regulatory effect on the gut microbiota. Our results revealed that G-Rg1 significantly increased the 5-hydroxyindoleacetic acid levels and activated the aryl hydrocarbon receptor (AHR) by enhancing intestinal permeability, modulating the gut microbiota composition, and influencing tryptophan metabolism. Therefore, G-Rg1 improved immune function and reduced liver inflammation and lipid deposition in the MASLD mouse model. In contrast, the effect of G-Rg1 was impaired upon removal of the gut microbiota. Furthermore, fecal microbiota transplantation in G-Rg1-treated mice improved MASLD. These finding s suggest that regulating the gut microbiota may play an important role in G-Rg1's ability to protect against MASLD. G-Rg1 may exert its anti-MASLD effects through the gut microbiota, tryptophan metabolism, AHR activation, and interleukin-22 signaling, offering a novel approach for G-Rg1-mediated MASLD treatment.}, }
@article {pmid40523286, year = {2025}, author = {Juul, FE and Bretthauer, M and Johnsen, PH and Samy, F and Tonby, K and Berdal, JE and Hoff, DAL and Ofstad, EH and Abraham, A and Seip, B and Wiig, H and Rognstad, &#xd8;B and Glad, IF and Valeur, J and Nissen-Lie, AE and Ness-Jensen, E and Lund, KMA and Skjevling, LK and Hanevik, K and Skudal, H and Melsom, EJ and Boyar, R and Cooper, TJ and Ranheim, TE and Riise, EM and Adami, HO and Kalager, M and Løberg, M and Garborg, KK}, title = {Fecal Microbiota Transplantation Versus Vancomycin for Primary Clostridioides difficile Infection : A Randomized Controlled Trial.}, journal = {Annals of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.7326/ANNALS-24-03285}, pmid = {40523286}, issn = {1539-3704}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile infection (CDI), but its role in primary CDI is unclear.<br><br>OBJECTIVE: To investigate the efficacy and safety of FMT in primary CDI.<br><br>DESIGN: Randomized, open-label, noninferiority, multicenter trial. (ClinicalTrials.gov: NCT03796650).<br><br>SETTING: Hospitals and primary care facilities in Norway.<br><br>PATIENTS: Adults with CDI (C difficile toxin in stool and &#x2265;3 loose stools daily) and no previous CDI within 365 days before enrollment.<br><br>INTERVENTION: FMT without antibiotic pretreatment versus oral vancomycin, 125 mg 4 times daily for 10 days.<br><br>MEASUREMENTS: The primary end point was clinical cure (firm stools or <3 bowel movements daily) at day 14 and no disease recurrence within 60 days with the assigned treatment alone.<br><br>RESULTS: Of 104 randomly assigned patients, 100 received FMT or the first dose of vancomycin and were eligible for analysis. Clinical cure and no disease recurrence within 60 days without additional treatment was observed in 34 of 51 patients (66.7%) with FMT versus 30 of 49 (61.2%) with vancomycin (difference, 5.4 percentage points [95.2% CI, -13.5 to 24.4 percentage points]; P for noninferiority < 0.001, rejecting the hypothesis that response to FMT is 25 percentage points lower than response to vancomycin). Eleven patients in the FMT group and 4 in the vancomycin group had additional C difficile treatment. Clinical cure at day 14 and no recurrence with or without additional treatment was observed in 40 of 51 patients (78.4%) with FMT and 30 of 49 (61.2%) with vancomycin (difference, 17.2 percentage points [95.2% CI, -0.7 to 35.1 percentage points]). No significant differences in adverse events were observed between groups.<br><br>LIMITATIONS: Open-label design and reliance on clinical end points.<br><br>CONCLUSION: FMT may be considered as first-line therapy in primary CDI.<br><br>PRIMARY FUNDING SOURCE: South-East Norway Health Trust.}, }
@article {pmid40522165, year = {2025}, author = {Huang, JN and Wen, B and Wang, ZN and Gao, JZ and Chen, ZZ}, title = {Microplastics Change the Food Utilization of Filter-Feeding Fish via Gut Microbiota.}, journal = {Environmental science &amp; technology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.est.5c02067}, pmid = {40522165}, issn = {1520-5851}, abstract = {Microplastics (MPs) are ubiquitous in aquatic environments, while their effects on filter-feeding fish are poorly understood. This study aims to explore how MPs change the feeding of planktivorous silver carp. After exposure to MPs, the utilization efficiency of zooplankton by carp increased from 28.45% to 38.63-40.20%, while that of phytoplankton decreased from 50.64% to 40.47-43.32%. MPs did not cause changes in the phytoplankton and zooplankton communities that carp consumed but altered its gut microbiota, leading to increased abundance of genes encoding proteases but decreased carbohydrase genes. Gut metabolomics further showed corresponding metabolic changes especially with increased levels of l-tyrosine, citrulline, succinic acid, and propionic acid, which are significantly correlated with the isotopic signatures of carp utilizing zooplankton. Germ-free zebrafish transplanted with feces of MPs-exposed carp showed metabolic changes like those of carp, verifying that the gut microbiota mediated the effects induced by MPs, while silver carp transplanted with feces of MPs-exposed carp exhibited increased protease activity and enhanced zooplankton utilization efficiency, confirming that MPs could alter its food utilization via gut microbiota. Our findings fill a knowledge gap regarding the ecological risk of MPs to the feeding of planktivorous fish, with potential cascading effects on aquatic ecosystems.}, }
@article {pmid40520768, year = {2025}, author = {Feng, Z and Burgermeister, E and Philips, A and Zuo, T and Wen, W}, title = {The gut virome in association with the bacteriome in gastrointestinal diseases and beyond: roles, mechanisms, and clinical applications.}, journal = {Precision clinical medicine}, volume = {8}, number = {2}, pages = {pbaf010}, pmid = {40520768}, issn = {2516-1571}, abstract = {The gut virome, an essential component of the intestinal microbiome, constitutes ∼0.1% of the total microbial biomass but contains a far greater number of particles than bacteria, with phages making up 90%-95% of this virome. This review systematically examines the developmental patterns of the gut virome, focusing on factors influencing its composition, including diet, environment, host genetics, and immunity. Additionally, it explores the gut virome's associations with various diseases, its interactions with gut bacteria and the immune system, and its emerging clinical applications.}, }
@article {pmid40520290, year = {2025}, author = {Meng, D and Kong, W and Cheng, S and Liu, H and Huang, C}, title = {Gut-brain-liver axis in growth hormone deficiency: role of microbiota-derived short-chain fatty acids in ethnic variability and therapeutic development.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1541654}, pmid = {40520290}, issn = {2296-2565}, mesh = {Humans ; *Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome/physiology ; *Liver/metabolism ; *Human Growth Hormone/deficiency ; Animals ; *Brain/metabolism ; }, abstract = {Growth hormone deficiency (GHD) is a pediatric endocrine disorder characterized by dysregulated growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis activity and gut microbiota imbalance. Emerging evidence highlights the gut-brain-liver axis as a critical modulator of growth, with microbiota-derived short-chain fatty acids (SCFAs) playing dual roles in GH suppression and IGF-1 enhancement. This review synthesizes preclinical and clinical data to address ethnic variability in microbiota composition and therapeutic challenges. Key findings reveal that Chinese GHD cohorts exhibit reduced Bifidobacterium and fecal butyrate, whereas Spanish cohorts show minimal differences, potentially due to dietary fiber intake (e.g., Prevotella-enriched diets in Asia) or methodological variations in microbiota sequencing. Mechanistically, propionate (>500 μM) inhibits pituitary GH synthesis via GPR41/43-cAMP signaling, while butyrate enhances hepatic IGF-1 through GPR109A-mediated IL-6 secretion and osteoblastic histone deacetylase (HDAC) inhibition. Interventions such as probiotics (e.g., Lactobacillus plantarum increased IGF-1 by 1.2-1.8-fold in murine models) and high-fiber diets demonstrate preclinical efficacy but face clinical barriers, including poor adherence (<30%) and limited GHD-specific trials. Fecal microbiota transplantation (FMT) shows hormonal restoration in animal models but induces gastrointestinal adverse effects (22% bloating, 15% diarrhea) in humans. Multi-omics approaches are proposed to identify biomarkers (e.g., low butyrate + elevated trimethylamine N-oxide). These approaches also aim to optimize precision therapies, such as nanoparticle-delivered SCFAs. This review underscores the need for multicenter randomized controlled trials to validate synbiotics or engineered microbial consortia, bridging mechanistic insights into the microbiota-SCFA-endocrine axis with clinical translation for GHD management.}, }
@article {pmid40519780, year = {2025}, author = {Marrocco, F and Khan, R and Reccagni, A and Lin, X and Delli Carpini, M and Iebba, V and D'Alessandro, G and Limatola, C}, title = {Fecal or bacterial transplantation in mice transfer environment-induced brain plasticity and associated behavioral changes.}, journal = {Frontiers in physiology}, volume = {16}, number = {}, pages = {1572854}, pmid = {40519780}, issn = {1664-042X}, abstract = {INTRODUCTION: Recent studies have shown that lifestyle factors, including diet and environmental stimuli, significantly alter the composition of gut microbiota and the metabolites they produce. Specifically, housing mice in an enriched environment (EE) enhances the production of short-chain fatty acids, which in part mediate the effects of EE on brain plasticity. In this study, we tested the hypothesis that the gut microbial composition of EE-exposed mice could be transplanted into mice housed in a standard environment (SE) to replicate the environmental effects on behavior, gene expression and neurogenesis.<br><br>METHODS: To test this hypothesis, we transplanted either a specific bacterial mixture or fecal material from EE-housed mice into SE-housed mice.<br><br>RESULTS: Our data show that both bacterial and fecal transplants reduce anxiety-like behaviors in mice. Additionally, we observed increased expression of hippocampal neurotrophins and enhanced neurogenesis.<br><br>DISCUSSION: These findings support the idea that gut microbiota influence brain functions, including anxiety-like behavior. Further research is necessary to clarify the underlying mechanisms. Moreover, the results suggest that fecal material transplantation (FMT) from individuals with healthy lifestyles may represent a promising strategy for the treatment of mood disorders.}, }
@article {pmid40519640, year = {2025}, author = {You, W and Ji, J and Wen, D and Wang, C and Sun, X and Zhao, P}, title = {Unlocking therapeutic potential of amlexanox in MASH with insights into bile acid metabolism and microbiome.}, journal = {Npj gut and liver}, volume = {2}, number = {}, pages = {}, pmid = {40519640}, issn = {3004-9806}, abstract = {Metabolic dysfunction-associated steatohepatitis (MASH) has become a global health issue associated with obesity and diabetes. It is becoming a leading cause of end-stage liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Despite its increasing prevalence, effective pharmacotherapies for MASH remain limited, underscoring the urgent need for novel interventions. Amlexanox, an inhibitor of noncanonical IκB kinases, has demonstrated potential in restoring insulin sensitivity and glucose homeostasis in obese mice and human patients, as shown in our earlier studies. Here, we aimed to assess the therapeutic potential of amlexanox in dyslipidemia-associated diseases, particularly MASH and HCC, and to elucidate the underlying mechanism. We employed GAN diet-fed Ldlr [-/-] mice, which simultaneously develop obesity, MASH, and atherosclerosis, to recapitulate human metabolic syndrome and associated complications. Amlexanox was administrated orally to these mice after disease onset to examine its therapeutic efficacy. Our study demonstrates that even a low dose of amlexanox significantly reversed MASH and nearly completely prevented the progression from MASH to HCC. Both phenotypic and transcriptomic studies revealed that amlexanox markedly improved MASH-related dyslipidemia, hepatic steatosis, inflammation, liver injury, and hepatic fibrosis. Furthermore, multi-omics analysis revealed that amlexanox enhances hepatic bile acid synthesis and promotes fecal bile acid excretion. Notably, amlexanox reprogrammed gut microbiota, robustly increasing the abundance of Akkermansia muciniphila, a probiotic known to improve metabolic dysfunction. These findings uncover the multifaceted therapeutic potential of amlexanox in treating MASH and atherosclerosis by targeting bile acid metabolism, gut microbiota, hepatic inflammation, and fibrosis. Our study highlights amlexanox as a promising candidate for clinical applications.}, }
@article {pmid40519616, year = {2025}, author = {Zhang, Y and Liang, S and Choi, S and Li, G}, title = {Effects of maternal rumen microbiota on the development of the microbial communities in the gastrointestinal tracts of neonatal sika deer.}, journal = {Journal of animal science and technology}, volume = {67}, number = {3}, pages = {619-635}, pmid = {40519616}, issn = {2055-0391}, abstract = {This study investigated whether the microbial assemblages in the gastrointestinal tracts (GITs) of sika deer calves can be manipulated by maternal rumen microbiota transplantation (MRMT). The results suggest that MRMT had no significant effect on the growth of calves but markedly lowered the duration of diarrhea and increased rumen fermentation in sika deer calves. Sequencing analysis of 16S rRNA gene amplicons revealed that MRMT increased the ability of some microbial taxa to colonize the GIT or enabled the colonization of others, which caused the ruminal microbial communities in sika deer calves to shift such that they resembled those of their mothers and promoted the temporal development of gut microbial diversity in deer calves. Moreover, after inoculation, 7 inoculum-dominant taxa (Butyrivibrio, Tenericutes, RFP12, SR1, Verrucomicrobia, Verruco_5, and WCHB1_41) and one inoculum-dominant taxon (Butyrivibrio) were significantly enriched in the rumen and feces of the sika deer calves, respectively. These data suggest that MRMT may be an effective approach for promoting microbial establishment in the GIT and preventing diarrhea in sika deer calves.}, }
@article {pmid40519460, year = {2025}, author = {Suvvari, TK and Vallurupalli, V and Koneru, KS and Ingawale, S and Yegurla, RR}, title = {The Lasting Imprint of Antibiotics on Gut Microbiota: Exploring Long-Term Consequences and Therapeutic Interventions.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e84114}, pmid = {40519460}, issn = {2168-8184}, abstract = {The widespread use of antibiotics has significantly impacted gut microbiota, often leading to long-term dysbiosis with profound health consequences. Antibiotics not only target pathogenic bacteria but also disrupt beneficial microbial communities, reducing diversity and increasing susceptibility to metabolic disorders, immune dysfunction, and opportunistic infections like Clostridioides difficile. The antibiotic-induced microbiota alterations can persist for weeks or even months post-treatment, contributing to ongoing health challenges. Restorative strategies, including probiotics, prebiotics, fecal microbiota transplantation, and dietary modifications, offer potential solutions to mitigate these effects. A balanced approach to antibiotic use, coupled with targeted interventions, is essential to preserving gut microbial health and minimizing long-term complications. Further research is needed to optimize therapeutic strategies and enhance patient outcomes. So, this editorial aims to examine the long-term consequences of antibiotic-induced gut microbiota disruption, highlight clinical and subclinical implications, and evaluate emerging therapeutic interventions aimed at microbiota restoration.}, }
@article {pmid40518557, year = {2025}, author = {Oppenheimer, M and Tao, J and Moidunny, S and Roy, S}, title = {Anxiety-like behavior during protracted morphine withdrawal is driven by gut microbial dysbiosis and attenuated with probiotic treatment.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2517838}, doi = {10.1080/19490976.2025.2517838}, pmid = {40518557}, issn = {1949-0984}, mesh = {Animals ; *Probiotics/administration &amp; dosage/therapeutic use ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Substance Withdrawal Syndrome/microbiology/psychology ; Mice ; *Anxiety/microbiology/etiology ; *Morphine/adverse effects ; Male ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Behavior, Animal ; Morphine Dependence ; }, abstract = {The development of anxiety during protracted opioid withdrawal heightens the risk of relapse into the cycle of addiction. Understanding the mechanisms driving anxiety during opioid withdrawal could facilitate the development of therapeutics to prevent negative affect and promote continued abstinence. Our lab has previously established the gut microbiome as a driver of various side effects of opioid use, including analgesic tolerance and somatic withdrawal symptoms. We therefore hypothesized that the gut microbiome contributes to the development of anxiety-like behavior during protracted opioid withdrawal. In this study, we first established a mouse model of protracted morphine withdrawal, characterized by anxiety-like behavior and gut microbial dysbiosis. Next, we used fecal microbiota transplantation (FMT) to show that gut dysbiosis alone is sufficient to induce anxiety-like behavior. We further demonstrated that probiotic therapy during morphine withdrawal attenuated the onset of anxiety-like behavior, highlighting its therapeutic potential. Lastly, we examined transcriptional changes in the amygdala of morphine-withdrawn mice treated with probiotics to explore mechanisms by which the gut-brain axis mediates anxiety-like behavior. Our results support the use of probiotics as a promising therapeutic strategy to prevent gut dysbiosis and associated anxiety during opioid withdrawal, with potential implications for improving treatment outcomes in opioid recovery programs.}, }
@article {pmid40518001, year = {2025}, author = {Xu, Y and Mo, Y and Zhou, W and Qin, M and Li, M and Yin, G and Yu, H and Chen, Y and Du, H and Jin, Y and Huang, H and Ma, C and Xia, J and Li, H and Xie, Z and Wang, P and Hong, Y}, title = {Sorafenib induces intestinal toxicity by disturbing gut microbiota and activating the LPS/TLR4/NF-κB signaling pathway in mice.}, journal = {Toxicology}, volume = {}, number = {}, pages = {154220}, doi = {10.1016/j.tox.2025.154220}, pmid = {40518001}, issn = {1879-3185}, abstract = {Sorafenib is a multitargeted tyrosine kinase inhibitor approved by the FDA as a standard first-line therapy for advanced hepatocellular carcinoma. Nevertheless, the high incidence rate of gastrointestinal (GI) adverse effects substantially limits its clinical application. The molecular mechanisms underlying the GI damage remain poorly understood. In this study, we explored the critical role of gut microbiota in sorafenib-induced intestinal toxicity using a mouse model and proposed a potential therapeutic intervention strategy. Sorafenib administration caused intestinal pathological damage, systemic inflammation, and oxidative stress in mice. Antibiotic (ABX) treatment and fecal microbiota transplantation (FMT) experiments demonstrated that the GI toxicity induced by sorafenib was mediated by the gut microbiota. 16S rRNA sequencing analysis revealed that sorafenib dramatically disturbed gut microbial homeostasis, leading to an increased abundance of Gram-negative bacteria and upregulated biosynthesis of lipopolysaccharide (LPS). Intestinal transcriptomic sequencing further indicated that sorafenib induced Gram-negative bacterial-derived LPS leakage via the compromised intestinal barrier and exacerbated inflammation via TLR4/NF-κB pathway activation. Notably, the TLR4-specific inhibitor TAK-242 effectively attenuated sorafenib-induced intestinal damage. Taken together, our study unveils a novel mechanism by which sorafenib exacerbates intestinal injury through gut microbiota dysbiosis and LPS/TLR4/NF-κB signaling pathway, while proposing TAK-242 as a promising therapeutic strategy. This study underscores the critical role of the gut microbiota in sorafenib-induced intestinal damage and offers new avenues for clinical intervention.}, }
@article {pmid40517921, year = {2025}, author = {Wang, Y and Huang, J and Tong, H and Jiang, Y and Jiang, Y and Ma, X}, title = {Nutrient Acquisition of Gut Microbiota: Implications for Tumor Immunity.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2025.06.003}, pmid = {40517921}, issn = {1096-3650}, abstract = {The gut microbiota is essential in colorectal cancer (CRC) development, progression, and therapeutic responsiveness through its metabolic acquisitions and immunomodulatory functions. The composition of gut microbiota is shaped by habitat filters such as oxygen availability, dietary components, and host-derived factors, which influence both bacterial colonization and metabolic strategies. Furthermore, microbial metabolism of carbohydrates, proteins, and lipids produces metabolites, including short-chain fatty acids (SCFAs), polyamines, ammonia, hydrogen sulfide, and secondary bile acids (BAs). These microbial metabolites can either support anti-tumor immune surveillance or promote tumorigenesis depending on their type, concentration, and the host context. Consequently, interventions such as high-fiber diets, prebiotic and probiotic supplementation, and fecal microbiota transplantation (FMT) have emerged as promising strategies to reshape the gut ecosystem and improve CRC treatment efficacy. This review summarizes current insights into microbial nutrient metabolism, discusses the immune-regulatory effects of key microbial metabolites, and explores microbiota-targeted strategies for enhancing antitumor efficacy. Understanding these interactions offers new therapeutic opportunities for cancer prevention and treatment.}, }
@article {pmid40517506, year = {2025}, author = {Li, Y and Yue, D and Zhao, Y and Liu, P and Li, M and Chen, J and Yan, X and Fan, L and Song, G and Tian, X and Lv, Y and Zhao, Q and Qiu, Y and Yan, X}, title = {Fecal microbiota transplantation alleviates female offspring's ovarian inflammation in arsenic and fluoride co-exposed rats through the PI3K/ Akt /NF-κB pathway.}, journal = {Ecotoxicology and environmental safety}, volume = {301}, number = {}, pages = {118508}, doi = {10.1016/j.ecoenv.2025.118508}, pmid = {40517506}, issn = {1090-2414}, abstract = {Numerous studies have shown that exposure to arsenic (As) or fluoride(F) can damage the reproductive system, but limited evidence exists regarding the combined toxicity and pathogenesis of As and F co-exposure in female reproduction. Moreover, the role of gut microbiota in mediating such toxicity remains unclear. This study investigated the effects of As and F co-exposure on ovarian development and the potential protective role of fecal microbiota transplantation (FMT). We established an animal model of ovarian injury induced via co-exposure to NaAsO2 and NaF from birth to postnatal day 120(PND120) and introduced FMT from PND60. Co-exposure reduced serum levels of estradiol(E2) and luteinizing hormone (LH), along with morphological alterations in ovarian tissue. Meanwhile, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear transcription factor-κB (NF-κB) pathway, a known mediator of inflammation-related ovarian dysfunction, was significantly upregulated. Interestingly, with prolonged exposure, the inflammatory indicators (Akt, IL-1β, IL-6, TNF-α) on PND120 were significantly higher than those on PND60. Notably, FMT alleviated ovarian inflammation, potentially by improving colonic barrier function, thereby indirectly mitigating ovarian damage. Taken together, this study reveals that NaAsO2 and NaF co-exposure induces progressive ovarian inflammation via the PI3K/Akt/NF-κB pathway, and that FMT may offer protective effects. Our findings provide new insights into the environmental risks to female reproductive health.}, }
@article {pmid40516560, year = {2025}, author = {Assmann, SL and Keszthelyi, D and Kimman, ML and Breukink, SO and , }, title = {Faecal incontinence core outcome set: an international Delphi consensus exercise among patients, health-care professionals, and researchers.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2468-1253(25)00013-5}, pmid = {40516560}, issn = {2468-1253}, abstract = {Faecal incontinence is a debilitating anorectal disorder that can severely affect a person's quality of life. The variability in reported outcomes in studies on treatments for faecal incontinence complicates the synthesis of evidence, thereby weakening treatment recommendations. Furthermore, the emphasis on clinical outcomes often neglects outcomes that are crucial to patients' daily lives. Incorporating diverse stakeholder perspectives, we aimed to develop a core outcome set (COS)-a minimum set of outcomes that should be measured in future studies evaluating the efficacy of a treatment in adults with faecal incontinence. Following guidelines from the COMET initiative, this study proceeded through three steps: identifying outcomes via patient interviews and a systematic literature review; ranking and refining outcomes through two rounds of Delphi surveys involving patients, health-care professionals, and researchers; and finalising the COS through a consensus meeting with relevant stakeholders. Round 1 of the Delphi survey included 109 participants (73 health-care professionals and researchers and 36 patients) and round 2 involved 74 participants (54 and 20, respectively). In both rounds, participants ranked the importance of potential outcomes on a 9-point Likert scale. Of the 58 outcomes that entered round 1 and the three that were later added, 27 outcomes were voted out and the remaining 34 were discussed during a consensus meeting to finalise the COS. The final COS encompasses 13 outcomes: seven quality of life-related outcomes (quality of life, influence on daily activities, social functioning, treatment satisfaction, enjoyment in life, embarrassment, and peace of mind) and six clinical outcomes (severity of faecal incontinence, number of faecal incontinence episodes, urgency, stool consistency, adverse events, and adherence to therapy). This study establishes what outcomes should be included in a COS for use in faecal incontinence research, but future research is needed to identify the appropriate measurement instruments for each outcome and to establish appropriate timing for their assessment, which will further refine outcome definitions before this COS can be implemented. Once these aspects are clarified, the COS can be adopted into faecal incontinence research, which we hope will ultimately improve clinical care.}, }
@article {pmid40514640, year = {2025}, author = {Almulla, AF and Maes, M}, title = {Peripheral Immune-Inflammatory Pathways in Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: Exploring Their Potential as Treatment Targets.}, journal = {CNS drugs}, volume = {}, number = {}, pages = {}, pmid = {40514640}, issn = {1179-1934}, support = {RA66/016//FF66 grant and a Sompoch Endowment Fund (Faculty of Medicine), MDCU/ ; BG-RRP-2.004-0007-&#x421;01//Strategic Research and Innovation Program for the Development of MU - PLOVDIV-(SRIPD-MUP)", Creation of a network of research higher schools, National plan for recovery and sustainability, European Union - NextGenerationEU/ ; }, abstract = {Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are major mental disorders linked to substantial morbidity. Traditional monoamine-based pharmacotherapies frequently produce inadequate outcomes for many patients. The elevated levels of treatment resistance require the exploration of new pharmacological targets. Evidence indicates that peripheral immune-inflammatory dysregulation, characterized by an imbalance between immunological responses and compensatory immune-regulatory systems (IRS/CIRS), together with increased oxidative and nitrosative stress (O&amp;NS), significantly contributes to the pathogenesis of these disorders. This review examines IRS/CIRS/O&amp;NS pathways as new drug targets and highlights novel pharmacological trials. Antiinflammatory drugs have been repurposed as augmentation strategies for the treatment of MDD/BD and SCZ, including nonsteroidal antiinflammatory medications, such as cyclooxygenase-2 (COX-2) inhibitors; cytokine-targeting biologics, such as tumor necrosis factor-α monoclonal antibodies; and minocycline, an antibiotic that attenuates neuroinflammation. N-acetylcysteine, curcumin, and omega-3 polyunsaturated fatty acids demonstrate some efficacy as augmentation therapies in MDD, likely by diminishing IRS activation and O&amp;NS. Strategies aimed at the gut-brain axis and gut dysbiosis, including fecal microbiota transplantation, are under investigation for their capacity to restore immunological homeostasis by improving gut barrier integrity and microbiome composition. This review examines new potential therapeutic targets arising from recent discoveries in neuro-immune interactions and oxidative stress, including particular lymphocyte surface markers, the CIRS, and intracellular network molecules in both affective and psychotic disorders. The evidence underscores the clinical importance of immune-targeted augmentation treatments in psychiatric disorders and supports the ongoing development of these novel pharmacotherapies within a precision medicine paradigm.}, }
@article {pmid40513921, year = {2025}, author = {Zhang, X and Sheng, N and Wang, Z and Cao, Y and Jiang, X and Yan, H and Cheng, F and Geng, T and Wei, K and Zhang, L and Gao, M and Zhou, G and Chen, P}, title = {Exploring the mechanism of Carbonized Typhae Pollen in treating blood stasis syndrome through metabolic profiling: the synergistic effect of hemostasis without blood stasis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120124}, doi = {10.1016/j.jep.2025.120124}, pmid = {40513921}, issn = {1872-7573}, abstract = {Removing blood stasis and stopping bleeding traditional Chinese medicines (RBSB-TCM) formed a unique class of TCM, characterized by vasodilating, removing stasis and hemostatic effects. Carbonized Typhae Pollen (CTP), derived from Typhae Pollen (TP) through carbonization, has emerged as a particularly valuable therapeutic agent. It has been widely used in clinical practice to treat hemorrhagic disorders caused by blood stasis syndrome (BSS). However, the potential mechanism for CTP to achieve the dual synergistic effect of promoting blood flow and hemostasis remains unclear.<br><br>AIM OF THE STUDY: From the standpoint of metabolite profiles, this study attempts to investigate the fundamental mechanism of CTP in the elimination of blood stasis and the cessation of bleeding.<br><br>MATERIALS AND METHODS: First, chemical constituents, absorbed constituents and metabolites in rats following oral administration of CTP were identified by ultra-high performance liquid chromatography coupled with the quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method combined with MetabolitePilot 2.0.4 software. Subsequently, the pharmacological effects of CTP were systematically investigated using rat models with BSS and zebrafish with cerebral hemorrhage. Specifically, the impact on coagulation function and histopathology in rats, as well as the effect on cerebral hemorrhage in zebrafish, were thoroughly evaluated. Untargeted metabolomics based on rat plasma was applied to analyze the metabolic profile changes, revealing the potential action mechanism. The underlying mechanism was furtherly confirmed by gut microbiome analysis and systemic molecular biology experiments.<br><br>RESULTS: 34 prototype chemicals and 71 metabolites from the liver, heart, spleen, lung, kidney, small intestine, uterus, and serum were found. CTP improved the abnormal coagulation system, promoted blood circulation, and reduced pathological damage caused by BSS. Plasma metabolomics revealed that BSS significantly altered bile acid (BA) metabolism and arachidonic acid (AA) metabolism. Gut microbiome analysis and fecal microbiota transplantation (FMT) experiments further demonstrated that CTP modulated the gut microbiota. This modulation promoted BA production and activated endothelial nitric oxide synthase (eNOS), leading to increased nitric oxide (NO) levels. These changes contributed to the therapeutic effect of CTP in removing blood stasis. Systemic molecular biology experiments showed that CTP activated key components of the AA metabolic pathway. It promoted PLC&#x3b3;1 phosphorylation, increased intracellular Ca[2+] levels, and upregulated COX-2 expression. In addition, CTP enhanced the production of AA-related metabolites, including 6-keto-prostaglandin F1&#x3b1; (6-keto-PGF1&#x3b1;), prostaglandin E2 (PGE2), and thromboxane B2 (TXB2). It also increased the transcription of AA metabolism-related genes, such as PLC&#x3b3;1, PTGS2a, PTGS2b, PTGIS, PTGES, TXBAS, and vWF.<br><br>CONCLUSIONS: CTP could promote the generation of AA metabolites through PLC&#x3b3;1/Ca[2+]/COX-2 to stop bleeding, while also enhancing eNOS activity and NO synthesis through gut microbiota-bile acid axis to remove blood stasis. These two effect were balanced to achieve hemostasis without blood stasis.}, }
@article {pmid40511533, year = {2025}, author = {Mo, X and Shen, L and Wang, X and Ni, W and Li, L and Xia, L and Liu, H and Cheng, R and Wen, L and Xu, J and Liu, L}, title = {Melatonin Mitigates Sarcopenic Obesity via Microbiota and Short-Chain Fatty Acids: Evidence From Epidemiologic and In Vivo Studies.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {3}, pages = {e13869}, pmid = {40511533}, issn = {2190-6009}, support = {82230112//National Natural Science Foundation of China/ ; 82273631//National Natural Science Foundation of China/ ; 2024M761026//China Postdoctoral Science Foundation/ ; 2022YFA0806100//National Key Research and Development Program of China/ ; }, mesh = {Animals ; *Melatonin/pharmacology/therapeutic use ; *Sarcopenia/drug therapy/epidemiology/etiology ; *Obesity/drug therapy/epidemiology ; *Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome/drug effects ; Humans ; Male ; Rats ; Middle Aged ; Female ; Case-Control Studies ; Aged ; }, abstract = {INTRODUCTION: Gut dysbiosis is closely related to the development of sarcopenic obesity (SO). Melatonin (MLT) regulates gut microbiota and promotes the production of short-chain fatty acids (SCFAs). However, whether MLT affects SO through the gut microbiota and SCFAs remains unclear. This study aimed to investigate the effect and mechanism of MLT in SO induced by a high-fat diet (HFD).<br><br>METHODS: First, a case-control study was conducted to explore the potential association between serum MLT levels and SO-related parameters in 31 patients. Next, rats fed with a HFD were orally administered with MLT for 16&#x2009;weeks, and obesity-related metabolic disorders and muscle atrophy were measured. 16S rRNA gene sequencing and gas chromatography-mass spectrometry were used to detect gut microbiota and SCFAs, respectively. Gut barrier integrity was assessed by the expression of the Muc-2 protein and tight junction proteins. Finally, faecal microbiota transplantation and SCFAs administration were performed to confirm the causal role of the gut microbiota and SCFAs in the effect of MLT on SO.<br><br>RESULTS: The serum levels of MLT decreased in patients with SO (29.87&#x2009;&#xb1;&#x2009;6.71 vs. 24.94&#x2009;&#xb1;&#x2009;5.68, p&#x2009;<&#x2009;0.01) and were closely associated with appendicular skeletal muscle mass index (r&#x2009;=&#x2009;0.3514, p&#x2009;<&#x2009;0.01) and handgrip strength (r&#x2009;=&#x2009;0.2824, p&#x2009;<&#x2009;0.05). MLT ameliorated obesity-related metabolic disorders (p&#x2009;<&#x2009;0.05), poor muscle mass (p&#x2009;<&#x2009;0.05), strength (p&#x2009;<&#x2009;0.05) and function (p&#x2009;<&#x2009;0.05) and muscle atrophy (p&#x2009;<&#x2009;0.05) in HFD-fed rats. MLT regulated HFD-induced gut dysbiosis, which was mainly characterized by increases in SCFAs-related bacteria and SCFAs (p&#x2009;<&#x2009;0.05). MLT recovered HFD-induced impairment of gut barrier integrity by promoting the expression levels of Muc-2, claudin-1, occludin and zonula occluden-1 proteins in the colon (p&#x2009;<&#x2009;0.05). Correlation analysis showed that SCFAs-related bacteria and SCFAs were negatively associated with SO. Faecal suspension from MLT-treated rats promoted the production of SCFAs in recipient rats (p&#x2009;<&#x2009;0.05). In addition, faecal suspension from MLT-treated rats partially mitigated metabolic disorders (p&#x2009;<&#x2009;0.05), poor muscle mass and function (p&#x2009;<&#x2009;0.05) and muscle atrophy (p&#x2009;<&#x2009;0.05) in recipient rats. SCFAs treatment alleviated the development of SO in HFD-fed rats by suppressing metabolic disorders (p&#x2009;<&#x2009;0.05), reducing muscle oxidative stress and inflammation (p&#x2009;<&#x2009;0.05) and promoting protein synthesis through the AKT/mTOR/p70S6k signalling pathway (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: MLT mitigated HFD-induced SO by regulating the gut microbiota and promoting the production of SCFAs. MLT might be a novel strategy for delaying the progression of SO.}, }
@article {pmid40510802, year = {2025}, author = {Tan, S and Peng, C and Lin, X and Peng, C and Yang, Y and Liu, S and Huang, L and Bian, Y and Li, Y and Xu, C}, title = {Clinical efficacy of non-pharmacological treatment of functional constipation: a systematic review and network meta-analysis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1565801}, pmid = {40510802}, issn = {2235-2988}, mesh = {Humans ; Acupuncture Therapy/methods ; *Constipation/therapy ; Fecal Microbiota Transplantation/methods ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: The purpose of this study is to compare the relative effectiveness and safety of non-pharmacological interventions for the treatment of functional constipation (FC).<br><br>METHODS: We searched Pubmed, Embase, Cochrane, and Web of Science databases for randomized controlled trials published from 2010 to November 2024. The quality of the included studies was evaluated using the Cochrane bias risk tool and Review Manager 5.4, and the evidence was graded using GRADEPro. A network meta-analysis (NMA) was conducted using R Studio, and the surface under the cumulative ranking curve (SUCRA) was used to rank the included drugs for each outcome measure to compare the clinical efficacy of different treatment methods for chronic functional constipation.<br><br>RESULTS: A total of 29 RCT studies were included, with a total of 4389 patients with functional constipation who were randomly assigned to receive placebo or one of the nine different non-pharmacological treatment methods. The assessment of bias risk showed that the bias risk of most included studies was low. The results showed that the first-ranked treatment method for clinical efficacy was acupuncture; the first-ranked treatment method for changes in spontaneous bowel movement (SBM) and complete spontaneous bowel movement (CSBM) was fecal microbiota transplantation (FMT); the first-ranked treatment method for changes in the Bristol Stool Form Scale (BSFS) score was FMT; the first-ranked treatment method for changes in the Patient Assessment of Constipation Quality of Life (PAC-QOL) score after treatment was the Vibration capsule; the first-ranked treatment method for changes in the Patient Assessment of Constipation Symptoms (PAC-SYM) score after treatment was percutaneous electrical stimulation; and the treatment method with the lowest incidence of adverse reactions was probiotics.<br><br>CONCLUSION: Based on the SUCRA values and NMA results, we found that FMT showed better effects and higher safety on BSFS scores, SBM, and CSBM. In addition, acupuncture showed a good clinical efficacy. We hypothesize that the combination of FMT and acupuncture may be an effective and safe treatment option for functional constipation, but further high-quality clinical studies are needed to confirm this.<br><br>https://www.crd.york.ac.uk/prospero/, identifier CRD42024625747.}, }
@article {pmid40510588, year = {2025}, author = {He, S and Chen, H and Xi, H and Sun, G and Du, B and Liu, X}, title = {Gut Microbiota-Derived Butyric Acid Alleviates Glucocorticoid-Associated Osteonecrosis of the Femoral Head via Modulating Inflammatory Cytokines in Bone Marrow Mesenchymal Stem Cells.}, journal = {Mediators of inflammation}, volume = {2025}, number = {}, pages = {8742817}, pmid = {40510588}, issn = {1466-1861}, mesh = {Animals ; *Butyric Acid/metabolism/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/physiology/drug effects ; Rats, Sprague-Dawley ; Rats ; *Mesenchymal Stem Cells/metabolism/drug effects ; *Glucocorticoids/adverse effects ; *Cytokines/metabolism ; Male ; *Osteonecrosis/chemically induced/metabolism/drug therapy ; }, abstract = {Background: The role of gut microbiota and its metabolites in regulating bone metabolism has been well established, with inflammatory immune responses potentially playing a critical role. Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH), caused by high-dose glucocorticoid use for inflammatory or immune-related diseases, is a prevalent condition of bone metabolic imbalance. However, the regulatory role and mechanisms of gut microbiota and its metabolites in the development and progression of GA-ONFH remain unclear. This study aims to investigate the intervention effects of gut microbiota and its metabolite butyric acid on GA-ONFH through a series of multi-omics in vitro and in vivo experiments. Methods: Sprague Dawley rats were randomly divided into four groups. The gut microbial composition of the groups was analyzed through 16S rDNA sequencing. Targeted metabolomics was employed to assess differences in short-chain fatty acids (SCFAs) among the groups. Butyric acid, identified as a key differential metabolite, was then selected for further exploration of its effects on bone marrow mesenchymal stem cells (BMSCs) and GA-ONFH rat models through in vitro and in vivo experiments. Results: 16S rDNA sequencing revealed alterations in gut microbiota structure in GA-ONFH rats. Micro-CT and HE staining demonstrated that depletion of gut microbiota with broad-spectrum antibiotics prior to GA-ONFH modeling exacerbated the disease's development. In contrast, fecal microbiota transplantation (FMT) was shown to alleviate GA-ONFH progression. Targeted metabolomics indicated that FMT mitigated the reduction in butyric acid levels induced by dexamethasone (DXM). Subsequent in vitro cell experiments confirmed that butyric acid promotes BMSC proliferation, migration, and osteogenic differentiation. RNA sequencing revealed that butyric acid regulates T cell-mediated inflammatory cytokine genes in BMSCs, while Western blot and immunofluorescence assays confirmed that butyric acid modulates the expression of TNF-α and IL-2/IL-4 in BMSCs. Finally, in vivo experiments demonstrated that butyric acid supplementation attenuated the progression of GA-ONFH and improved the expression of inflammation-related cytokines in femoral head tissue. Conclusions: Our study demonstrates that gut microbiota depletion exacerbates GA-ONFH, while FMT restores butyric acid levels and alleviates disease severity. Butyric acid reduced the expression of TNF-α and IL-2 while increasing the level of IL-4 in vivo and in vitro, thereby improving the local inflammatory environment of the femoral head and alleviating the progression of GA-ONFH. These findings highlight that reduction in butyric acid levels due to gut microbiota dysbiosis is a crucial factor in the progression of GA-ONFH.}, }
@article {pmid40509521, year = {2025}, author = {Zhang, M and Wang, W and Li, W and Wang, Z and Bi, K and Li, Y and Wu, Y and Zhao, Y and Yang, R and Du, Q}, title = {Ultrasonic-Assisted Extraction of Polysaccharides from Brassica rapa L. and Its Effects on Gut Microbiota in Humanized Mice.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, doi = {10.3390/foods14111994}, pmid = {40509521}, issn = {2304-8158}, support = {32260586//the National Natural Science Foundation of China - Regional Fund Project/ ; }, abstract = {This study optimized ultrasound-assisted extraction (UAE) for polysaccharide isolation from Brassica rapa L. using Box-Behnken design, achieving a maximum yield of 41.12% under conditions of 60 °C, 60 min, 175 W ultrasonic power, and 30 mL/g liquid-solid ratios. The crude polysaccharide (BRAP) was purified via DEAE-52 cellulose and Sephadex G-100 chromatography, yielding BRAP1-1 with the highest recovery rate. Structural analyses (FT-IR, HPGPC, SEM, SEC-MALLS-RI) identified BRAP1-1 as a β-glycosidic pyranose polysaccharide (32.55 kDa) composed of fucose, rhamnose, arabinose, galactose, and galacturonic acid (molar ratio 0.81:4.30:3.61:1.69:89.59). In a humanized mouse model via fecal microbiota transplantation (FMT), BRAP1-1 significantly increased α-diversity indices (ACE, Chao1; p < 0.05) and altered β-diversity, with PCA explaining 73% variance (PC1: 60.70%, PC2: 13.53%). BRAP1-1 elevated beneficial genera (Lysinibacillus, Solibacillus, Bacteroides, etc.) while suppressing pathogens (Treponema, Flavobacterium, etc.). Six genera, including [Eubacterium]_coprostanoligenes_group and Bacteroidales (p < 0.05), correlated with acetic/propionic acid production. These findings demonstrate BRAP1-1's potential to modulate gut microbiota composition and enhance intestinal homeostasis.}, }
@article {pmid40509464, year = {2025}, author = {Gong, H and Zhao, H and Mao, X}, title = {Sea Cucumber Hydrolysates Alleviate Cognitive Deficits in D-Galactose-Induced C57BL/6J Aging Mice Associated with Modulation of Gut Microbiota.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, doi = {10.3390/foods14111938}, pmid = {40509464}, issn = {2304-8158}, support = {2023YFF1104502//National Key R&amp;D Program of China/ ; }, abstract = {As the global elderly population is rising, concerns about cognitive decline and memory loss are becoming urgent. This study evaluated the potential of sea cucumber hydrolysates (SCH) from Stichopus japonicus in alleviating cognitive deficits using a D-galactose-induced murine aging model. The effects of SCH on behavior, hippocampal morphology, gut microbiota, hippocampal cholinergic system, brain-derived neurotrophic factor (BDNF) signaling, and neuroinflammatory pathways were investigated. Results showed that SCH ameliorated learning and memory deficits and reduced neuronal damage in aging mice. SCH also modulated gut microbiota, along with increased fecal short-chain fatty acids levels. Functional prediction revealed that alterations in gut microbiota were related to signal transduction. Further, SCH enhanced hippocampal cholinergic function through elevating acetylcholine (ACh) levels and inhibiting acetylcholinesterase (AChE) activity and activated BDNF signaling, consistent with predictions of gut microbiota function. Restoration of cholinergic homeostasis and transmission of the BDNF pathway might contribute to the inhibition of hippocampal neuroinflammation via suppressing microglial activation and the nuclear factor kappa-B (NF-κB) pathway. In summary, SCH attenuated cognitive deficits through suppressing neuroinflammation, which might be correlated with the signal transduction caused by regulating gut microbiota. Further validation will be conducted through microbiota depletion and fecal microbiota transplantation. These findings suggest that SCH is a promising functional component for counteracting aging-related cognitive deficits.}, }
@article {pmid40509391, year = {2025}, author = {Zang, R and Zhou, R and Li, Y and Liu, Z and Wu, H and Lu, L and Xu, H}, title = {Oleuropein Regulates Bile Acid Metabolism via Modulating the Gut Microbiota, Thereby Alleviating DSS-Induced Ulcerative Colitis in Mice.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, doi = {10.3390/foods14111863}, pmid = {40509391}, issn = {2304-8158}, abstract = {The pathogenesis of ulcerative colitis (UC) involves genetic, immunological, and environmental factors as well as gut microbiota dysbiosis. As a natural antioxidant with various pharmacological activities widely present in Oleaceae plants, oleuropein (OLE) exhibits anti-inflammatory, anti-tumor, antiviral, hypoglycemic, and cardioprotective effects. It has been validated that OLE extracted from olive oil can ameliorate UC. However, it remains unclear if and how OLE modulates the gut microbiota in the alleviation of UC. Therefore, this study was conducted to explore the mechanisms for OLE to alleviate UC induced by dextran sulfate sodium (DSS), with the focus placed on its regulatory function in the gut microbiota. The results indicated that OLE mitigated DSS-induced UC by enhancing the intestinal barrier function, reshaping the gut microbiota, and modulating bile acid metabolism. The fecal microbiota transplantation (FMT) experiment results further confirmed that the protective effect of OLE against UC could be mediated by alterations in the gut microbiota and their metabolites induced by OLE. Additionally, OLE increased the abundance of Lactobacillus and certain bile acid metabolites in the colon, including hyodeoxycholic acid (HDCA). HDCA could upregulate the expression of ZO-1 and claudin-3, restoring intestinal barrier integrity. Simultaneously, HDCA could inhibit the activation of the nuclear factor kappa-B (NF-κB) signaling pathway in the colon and relieve colonic inflammation. Overall, it was corroborated that OLE alleviated DSS-induced UC by modulating the gut microbiota and altering bile acid metabolism.}, }
@article {pmid40508089, year = {2025}, author = {Ai, P and Xu, S and Yuan, Y and Xu, Z and He, X and Mo, C and Zhang, Y and Yang, X and Xiao, Q}, title = {Targeted Gut Microbiota Modulation Enhances Levodopa Bioavailability and Motor Recovery in MPTP Parkinson's Disease Models.}, journal = {International journal of molecular sciences}, volume = {26}, number = {11}, pages = {}, doi = {10.3390/ijms26115282}, pmid = {40508089}, issn = {1422-0067}, support = {82171246//National Natural Science Foundation of China/ ; 82371251//National Natural Science Foundation of China/ ; 2022YFE0210100//National Key R&amp;D Program of China/ ; 22QA1405700//Shanghai Rising-Star Program/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Levodopa/pharmacokinetics/pharmacology/therapeutic use ; Mice ; Fecal Microbiota Transplantation ; Biological Availability ; Male ; Humans ; Disease Models, Animal ; *Parkinson Disease/drug therapy/metabolism ; Dopamine/metabolism ; Mice, Inbred C57BL ; Female ; }, abstract = {Emerging evidence highlights the gut microbiota as a pivotal determinant of pharmacological efficacy. While Enterococcus faecalis (E. faecalis)-derived tyrosine decarboxylases (tyrDCs) are known to decarboxylate levodopa (L-dopa), compromising systemic bioavailability, the causal mechanisms underlying microbiota-mediated pharmacodynamic variability remain unresolved. In our study, we employed antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) to interrogate microbiota-L-dopa interactions in MPTP-induced Parkinson's disease (PD) mice. The study demonstrated that antibiotic-mediated microbiota depletion enhances L-dopa bioavailability and striatal dopamine (DA) level, correlating with improved motor function. To dissect clinical heterogeneity in the L-dopa response, PD patients were stratified into moderate responders and good responders following standardized L-dopa challenges. In vitro bioconversion assays revealed greater L-dopa-to-DA conversion in fecal samples from moderate responders versus good responders. FMT experiments confirmed mice receiving good-responder microbiota exhibited enhanced L-dopa bioavailability, higher striatal DA concentrations, and a heightened therapeutic effect of L-dopa relative to moderate-responder recipients. Collectively, our study provided evidence that the gut microbiota directly modulates L-dopa metabolism and microbial composition determines interindividual therapeutic heterogeneity. Targeted microbial modulation-through precision antibiotics or donor-matched FMT-is a viable strategy to optimize PD pharmacotherapy, supporting the potential for microbiota-targeted adjuvant therapies in PD management.}, }
@article {pmid40507919, year = {2025}, author = {Belvončíková, P and Macáková, K and Tóthová, N and Babál, P and Tarabčáková, L and Gardlík, R}, title = {Investigating the Role of Gut Microbiota in the Pathogenesis and Progression of Rheumatoid Arthritis in a Collagen-Induced Arthritis Mouse Model.}, journal = {International journal of molecular sciences}, volume = {26}, number = {11}, pages = {}, doi = {10.3390/ijms26115099}, pmid = {40507919}, issn = {1422-0067}, support = {APVV-21-0370//Slovak Research and Development Agency/ ; VEGA 1/0706/25//Ministry of Education, Science, Research and Sport of the Slovak Republic/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Arthritis, Rheumatoid/microbiology/pathology/therapy/etiology ; *Arthritis, Experimental/microbiology/pathology/therapy ; Mice ; Disease Models, Animal ; RNA, Ribosomal, 16S/genetics ; Disease Progression ; Humans ; Mice, Inbred DBA ; Male ; Fecal Microbiota Transplantation ; Female ; }, abstract = {Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder whose precise etiology remains unclear, though growing evidence implicates gut microbiota in its pathogenesis. This study aimed to investigate the role of gut microbiota in the onset and progression of RA by employing fecal microbiota transplantation (FMT) in a collagen-induced arthritis (CIA) mouse model using DBA/1J and Aire[-]/[-] strains. Mice received FMT from healthy donors, treatment-naïve RA patients, or treated RA patients in relapse, followed by assessment of microbiota composition via 16S rRNA sequencing, arthritis severity scoring, histological evaluations, and systemic inflammatory markers. The findings revealed distinct microbiota clustering patterns post-FMT across experimental groups, highlighting strain-specific colonization effects. Notably, genera such as Bifidobacterium and Paraprevotella correlated positively with arthritis severity in DBA/1J mice, whereas Corynebacterium, Enterorhabdus, and Odoribacter exhibited negative correlations, suggesting potential protective roles. Despite these microbial differences, minor variations in arthritis scores, paw inflammation, or systemic inflammation were observed among FMT groups. This indicates that although gut microbiota alterations are associated with RA pathogenesis, further investigation with larger cohorts and comprehensive sequencing approaches is essential to elucidate the therapeutic potential of microbiome modulation in autoimmune diseases.}, }
@article {pmid40506454, year = {2025}, author = {Runge, S and von Zedtwitz, S and Maucher, AM and Bruno, P and Osbelt, L and Zhao, B and Gernand, AM and Lesker, TR and Gräwe, K and Rogg, M and Schell, C and Boerries, M and Strowig, T and Andrieux, G and Hild, B and Rosshart, SP}, title = {Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {5301}, pmid = {40506454}, issn = {2041-1723}, support = {491676693//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 256073931//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 446316360//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 431984000//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 241702976//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 438496892//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 501370692//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 256073931//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 256073931//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 491676693//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 259373024//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 431984000//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 441891347//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 471011418//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 493802833-P7//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 390874280//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 2023.010.1//Wilhelm Sander-Stiftung (Wilhelm Sander Foundation)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology/physiology ; Mice ; Phenotype ; Specific Pathogen-Free Organisms ; Mice, Inbred C57BL ; Male ; Female ; *Fecal Microbiota Transplantation/methods ; Models, Animal ; }, abstract = {Conventional laboratory mice housed under specific pathogen-free (SPF) conditions are the standard model in biomedical research. However, in recent years, many rodent-based studies have been deemed irreproducible, raising questions about the suitability of mice as model organisms. Emerging evidence indicates that variability in SPF microbiota plays a significant role in data inconsistencies across laboratories. Although efforts have been made to standardize microbiota, existing microbial consortia lack the complexity and resilience necessary to replicate interactions in free-living mammals. We present a robust, feasible and standardizable approach for transplanting natural gut microbiota from wildlings into laboratory mice. Following engraftment, these TXwildlings adopt a structural and functional wildling-like microbiota and host physiology toward a more mature immune system, with characteristics similar to those of adult humans. We anticipate that adopting wild mouse-derived microbiota as standard for laboratory mouse models will improve the reproducibility and generalizability of basic and preclinical biomedical research.}, }
@article {pmid40500780, year = {2025}, author = {Liu, J and Jing, C and Guo, Y and Shang, Z and Zhang, B and Zhou, X and Zhang, J and Lian, G and Tian, F and Li, L and Chen, Y}, title = {The central signaling pathways related to metabolism-regulating hormones of the gut-brain axis: a review.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {648}, pmid = {40500780}, issn = {1479-5876}, support = {ZR2022MH085//Natural Science Foundation of Shandong Province/ ; ZR2022MH070//Natural Science Foundation of Shandong Province/ ; 202134027//Jinan Science and Technology Bureau/ ; }, abstract = {Obesity is a widespread metabolic disorder linked to various conditions, including type 2 diabetes, hypertension, fatty liver disease, sleep apnea, and hyperuricemia. It significantly impacts quality of life and economic productivity. Traditional methods like diet and lifestyle changes often fail to produce substantial weight loss. Consequently, emerging treatments such as anti-obesity medications, bariatric surgery, and fecal microbiota transplantation are becoming more prominent. Recent research emphasizes the role of hormones that communicate with the hypothalamus through the gut-brain axis, affecting appetite, insulin secretion, and body weight via specific signaling pathways. This review explores the role of key gastrointestinal hormones (GLP-1, PYY, ghrelin, CCK, GIP, leptin, and bile acids) and their signaling pathways in metabolic regulation. The present research systematically evaluates the impact of bariatric surgery on appetite modulation and certain metabolic functions through key signaling pathways, including GLP-1R, GHS-R1a, and FXR/TGR5.}, }
@article {pmid40505989, year = {2025}, author = {Mehta, N and Little, K and Woodworth, MH and Goodenough, D and Dhonau, R and Fridkin, SK}, title = {Evaluating Disparities in Recurrent Clostridioides difficile Infection (CDI) and Fecal Microbiota Transplant (FMT) Treatment using Geospatial and Social Vulnerability Analytic Tools.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2025.05.028}, pmid = {40505989}, issn = {1528-0012}, }
@article {pmid40505847, year = {2025}, author = {Yadav, A and Tadas, M and Kale, M and Wankhede, N and Umekar, M and Kotagale, N and Taksande, B}, title = {Gut Microbiota and Behavioral Ontogeny in Autism Spectrum Disorder: A Pathway to Therapeutic Innovations.}, journal = {Physiology &amp; behavior}, volume = {}, number = {}, pages = {114989}, doi = {10.1016/j.physbeh.2025.114989}, pmid = {40505847}, issn = {1873-507X}, abstract = {Autism Spectrum Disorder (ASD) is a multifaceted neurodevelopmental condition characterized by deficits in social communication, repetitive behaviors, and restricted interests. Emerging evidence suggests that gut-brain axis a dynamic, bidirectional communication network between gut microbiota and central nervous system, is critical in shaping behavioral ontogeny in ASD. Dysbiosis of gut microbiota, commonly observed in individuals with ASD, has been associated with alterations in neurodevelopmental trajectories and symptom severity. Furthermore, disturbances in maternal microbiome during pregnancy are increasingly recognized as key factors influencing fetal brain development, potentially heightening risk of ASD and behavioral manifestations. Mechanistic research reveals that gut-derived metabolites modulate blood-brain barrier integrity, neuroinflammatory processes, and neuronal circuit formation, contributing to behavioral outcomes. These findings emphasize gut microbiota's profound influence on emergence and progression of ASD-related behaviors. Promising therapeutic strategies, including probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, have demonstrated potential in modulating the gut microbiome and improving behavioral symptoms in ASD. However, challenges such as individual variability in microbiome composition, limited clinical evidence, and an incomplete understanding of causative mechanisms remain significant barriers to clinical translation. This review explores the interplay between gut microbiota and ASD-associated behaviors, focusing on key mechanisms such as microbial regulation of neurotransmitter production, immune signaling, and neuroinflammation. It further highlights gut microbiota's potential as a modifiable factor influencing neurodevelopmental and behavioral outcomes in ASD. By advancing our understanding of gut-brain axis, we can pave the way for personalized and targeted interventions aimed at improving behavioral ontogeny and developmental trajectories in individuals with ASD.}, }
@article {pmid40505719, year = {2025}, author = {Zhu, X and Xu, Y}, title = {Gut microbiome contributes to 6PPD-Quinone induced cognitive impairment through PI3K/Akt signaling.}, journal = {Toxicology}, volume = {}, number = {}, pages = {154217}, doi = {10.1016/j.tox.2025.154217}, pmid = {40505719}, issn = {1879-3185}, abstract = {Studies show that N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) accumulates in the central nervous system, but its role in cognitive impairment and underlying mechanisms remain unclear. Morris water maze assay revealed that 6-PPDQ significantly impairs cognitive function, particularly learning and memory. HE staining revealed alterations in the hippocampal DG and CA3 regions of exposed mice, including sparse cell arrangement, blurred boundaries, nuclear condensation, and a reduction in Nissl bodies. Fecal microbiota transplantation from 6-PPDQ-exposed mice to normal mice induced cognitive deficits and hippocampal pathological damage. Western Blot assay showed that 6-PPDQ exposure resulted in inhibition of PI3K/AKT signaling. Moreover, blunted PI3K/AKT signaling was observed in mice transplanted with 6-PPDQ-associated mice fecal microbiota. Further analysis of 16S rDNA assay identified a total of 30 differential bacteria at the genus level, including 8 upregulated bacteria such as g_Helicobacter and 22 downregulated bacteria such as g_Prevotellaceae_NK3B31_group. In conclusion, this study uncovers gut microbiome mediates 6PPD-Q-induced cognitive impairment through inhibiting of PI3K/Akt signaling, and provides a basis for further investigation into gut microbiome's protective effects on 6-PPDQ-induced nervous system injury.}, }
@article {pmid40502301, year = {2025}, author = {Bhandari, P and Berezovskiy, R and Makhani, S and Gausman, V and Rastogi, N and Braude, S}, title = {Discordance in Clinical Indicators With Sequential Fecal Microbiota Transplantation: A Case of Fulminant Clostridioides Difficile Infection.}, journal = {ACG case reports journal}, volume = {12}, number = {6}, pages = {e01731}, pmid = {40502301}, issn = {2326-3253}, abstract = {Fulminant Clostridioides difficile infection (CDI) is a rare, severe type of CDI, often associated with extended hospitalizations, significant healthcare costs, and elevated mortality rates. Fecal microbiota transplantation remains an effective treatment modality for patients with fulminant CDI, with high cure rates reported after multiple treatments. Stool frequency, pseudomembrane resolution, and inflammatory markers are routinely monitored to evaluate disease severity and treatment responsiveness. Our case highlights a discordance in these indicators and demonstrates C-reactive protein as an important marker in assessing residual colitis and disease resolution. Comprehensive scoring systems should consider incorporating C-reactive protein and other biomarkers to optimize CDI management.}, }
@article {pmid40502184, year = {2025}, author = {Verna, G and De Santis, S and Islam, B and Sommella, EM and Licastro, D and Zhang, L and De Almeida Celio, F and Merciai, F and Caponigro, V and Campiglia, P and Pizarro, TT and Chieppa, M and Cominelli, F}, title = {A missense mutation in Muc2 promotes gut microbiome- and metabolome-dependent colitis-associated tumorigenesis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.05.31.657160}, pmid = {40502184}, issn = {2692-8205}, abstract = {UNLABELLED: Colitis-associated cancer (CAC) arises from a complex interplay between host and environmental factors, including the gut microbiome. Since ulcerative colitis (UC), a significant risk factor for CAC, is rising in prevalence worldwide, an integrative approach is essential to identify potential triggers linking inflammation to cancer. In the present study, we investigated the role of the gut microbiome using Winnie mice, a UC-like model with a relevant missense mutation in the Muc2 gene. Upon transfer from a conventional (CONV) to a specific-pathogen-free (SPF) facility, Winnie mice exhibited a more severe colitis phenotype, and notably, spontaneous CAC as early as four weeks of age, which progressively worsened over time. In contrast, CONV Winnie developed only mild colitis but with no overt signs of tumorigenesis. Notably, when rederived into germ-free (GF) conditions, SPF Winnie mice were protected from colitis or colon tumor development, indicating an essential role for the gut microbiome in the initiation and progression of CAC in these mice. Using shotgun metagenomics, metabolomics, and lipidomics, we identified a distinct pro-inflammatory microbial and metabolic signature that potentially drives the transition from colitis to CAC. Fecal microbiota transplantation (FMT), using either SPF Winnie or WT (Bl/6) donors into GF Winnie recipients, demonstrated that while colitis developed regardless of donor, only FMT from SPF Winnie donors resulted in CAC, revealing a microbiota-driven, host-specific susceptibility to tumorigenesis in Winnie mice. Our studies present a novel and relevant model of CAC, providing further evidence that the microbiome plays a key role in the pathogenesis of CAC, thereby challenging the concept of colon cancer as a strictly non-transmissible disease.<br><br>LAY SUMMARY: This study reveals a distinct metagenomic, metabolomic, and lipidomic profile associated with tumorigenesis in a murine model of ulcerative colitis, highlighting the risks of specific intestinal dysbiosis in genetically predisposed subjects.<br><br>WHAT YOU NEED TO KNOW: Background and context: Colitis-associated colorectal cancer arises from complex host-environment interactions, including gut microbiome influences, driving chronic inflammation, with the intestinal lumen environment remaining a largely unexplored potential risk factor in cancer development.New findings: Winnie mice in specific pathogen-free conditions developed severe colitis, and a novel juvenile colon dysplasia and cancer, with gut microbiome changes driving colitis-associated cancer initiation and progression.Limitations: We identified a pro-inflammatory microbial/metabolic signature promoting colitis-to-CAC transition in Winnie mice, with FMT confirming microbiota-driven tumor susceptibility. However, further research is needed to pinpoint the key bacteria-metabolite-lipid combination driving CAC.Clinical research relevance: This newly characterized microbiota-metabolome-based model of CAC, challenges the dogma of cancer as a non-transmittable disease, providing a foundation for developing microbiota-based strategies for CAC prevention and treatment.Basic research relevance: Unlike genetic or chemically induced models, the Winnie mouse model uniquely serves as a dual model for spontaneous colitis and juvenile CAC, offering a fast, 100% penetrant phenotype that enhances reliability, accelerates research, and provides valuable insights into IBD and CAC.}, }
@article {pmid40501499, year = {2025}, author = {Chen, L and Song, Y and Huang, Y and Hu, J and Meng, Y and Yuan, M and Zheng, G and Wang, X and Zhang, C and Qiu, Z}, title = {Cornus officinalis Extract Ameliorates Fructose-Induced Hepatic Steatosis in Mice by Sustaining the Homeostasis of Intestinal Microecology and Lipid Metabolism.}, journal = {Food science &amp; nutrition}, volume = {13}, number = {6}, pages = {e70425}, pmid = {40501499}, issn = {2048-7177}, abstract = {Cornus officinalis Sieb. et Zucc. (Cornus officinalis), an edible natural plant fruit, has beneficial effects on a multitude of metabolic diseases, but the mechanism to improve hepatic steatosis remains elusive. In this study, the curative effect of Cornus officinalis extract (COE) is evaluated in a fructose-induced NAFLD mouse model using biochemical indicators monitoring, histological staining, 16S rRNA sequencing analysis, and fecal microbiota transplantation. Our results showed that COE attenuates hepatic steatosis in fructose-fed mice. Mechanistically, COE repairs intestinal barrier damage and gut flora dysbiosis to suppress proinflammatory microbe-derived metabolite transportation to the liver, thus inhibiting the hepatic inflammation and lipid metabolic dysfunction. Notably, transplantation of fecal microbiota isolated from the fructose-fed mice could reverse the beneficial effect of COE on attenuating NAFLD. Therefore, our study demonstrates that COE delays the progression of fructose-driven NAFLD by suppressing lipid metabolic dysfunction and gut microbiota-mediated liver inflammation, highlighting the potential of C. officinalis as a resource for the treatment of NAFLD drugs.}, }
@article {pmid40501442, year = {2025}, author = {Maor, M and Levy Barazany, H and Kolodkin-Gal, I}, title = {The ladder of regulatory stringency and balance: an application to the US FDA's regulation of bacterial live therapeutics.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2517377}, doi = {10.1080/19490976.2025.2517377}, pmid = {40501442}, issn = {1949-0984}, mesh = {Humans ; United States ; United States Food and Drug Administration/legislation &amp; jurisprudence ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Bacteria/genetics ; Gastrointestinal Microbiome ; }, abstract = {The three main types of live bacterial therapies - probiotics, fecal/microbiome transplants, and engineered bacterial therapies - hold immense potential to revolutionize medicine. While offering targeted and personalized treatments for various diseases, these therapies also carry risks such as adverse immune reactions, antibiotic resistance, and the potential for unintended consequences. Therefore, developing and deploying these therapies necessitates a robust regulatory framework to protect public health while fostering innovation. In this paper, we propose a novel conceptual tool - the Ladder of Regulatory Stringency and Balance-which can assist in the design of robust regulatory regimes which encompass medicine practices based not only on definitive Randomized Controlled Trials (RCTs), but also on meta-analyses, observational studies, and clinicians experience. Regulatory stringency refers to the strictness of regulations, while regulatory balance concerns the degree of alignment between the regulatory framework governing a technology and the actual risks posed by specific products within that technology. Focusing on the US regulatory environment, we subsequently position the three types of live bacterial therapies on the Ladder. The insight gained from this exercise demonstrates that probiotics are generally positioned at the bottom of the Ladder, corresponding to low-stringency regulation, with a proportionate regulatory balance. However, probiotics intended for high-risk populations are currently subject to low-stringency regulations, resulting in under-regulation. Our analysis also supports the conclusion that fecal microbiota transplants (FMT) for recurrent Clostridium difficile infection should be positioned close to but below the threshold for under regulation by the U.S. Food and Drug Administration (FDA), and we recommend improved donor screening procedures, preservation and processing, storage, and distribution. Our framework can serve as a scale to assess regulatory gaps for live bacterial therapies and to identify potential solutions where such gaps exist.}, }
@article {pmid40500750, year = {2025}, author = {Yang, B and Li, X and Wang, J and Xu, Y and Wang, L and Wu, Z and Zhao, D and Huang, L and Li, N and Chen, Q and Liu, Z}, title = {The efficacy and safety of fecal microbiota transplantation in the treatment of sarcopenia: a retrospective study.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {645}, pmid = {40500750}, issn = {1479-5876}, support = {2022YFA1304100//National Key R&amp;D Program of China/ ; 2022YFC2010101//National Key R&amp;D Program of China/ ; 82470701//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Sarcopenia/therapy/physiopathology/microbiology ; *Fecal Microbiota Transplantation/adverse effects ; Male ; Female ; Aged ; Retrospective Studies ; Treatment Outcome ; Middle Aged ; Resistance Training ; Inflammation ; }, abstract = {BACKGROUND: Sarcopenia, a prevalent geriatric syndrome, is influenced by factors such as inflammation, immune deficiency, and oxidative stress. In elderly individuals, alterations in the microbiome, including reduced biodiversity and functional changes, significantly contribute to the progression of the disease. Targeting the gut-muscle axis has emerged as a promising therapeutic strategy to mitigate age-related muscle atrophy and dysfunction.<br><br>METHODS: This study employed fecal microbiota transplantation (FMT) to restore intestinal homeostasis in patients with sarcopenia. Muscle mass was measured using bioelectrical impedance analysis, while muscle function was assessed through grip strength and the five-time sit-to-stand test. Inflammatory markers, including tumor necrosis factor-&#x3b1; (TNF-&#x3b1;) and C-reactive protein (CRP), were also analyzed. Eighty-seven patients received resistance training (RT) treatment, while eighty-five patients received FMT combined with RT treatment, with a follow-up period of 24 weeks.<br><br>RESULTS: After 24 weeks, the resistance training (RT) group showed a partial remission (PR) rate of 54.7% and a complete remission (CR) rate of 32.4%. The FMT plus RT group demonstrated a PR rate of 66.5% and a CR rate of 46.7%. Significant improvements induced by FMT treatment were observed in clinical markers of muscle mass, function, and inflammation.<br><br>CONCLUSIONS: These results underscore the promise of microbial-based therapies, including fecal microbiota transplantation (FMT), as groundbreaking strategies for addressing sarcopenia. The research indicates that integrating FMT with resistance training could improve muscle mass and function while alleviating inflammation in sarcopenia patients, presenting a hopeful avenue for effective management of the condition.}, }
@article {pmid40503501, year = {2023}, author = {Kim, SY}, title = {[Gut Microbiota and Obesity].}, journal = {The Korean journal of helicobacter and upper gastrointestinal research}, volume = {23}, number = {4}, pages = {240-246}, pmid = {40503501}, issn = {2671-826X}, abstract = {Obesity is a global health concern associated with a wide range of diseases, including diabetes, metabolic syndrome, fatty liver, and cardiovascular conditions. Recent studies highlight the significant role of gut microbiota in obesity. Research indicates notable changes in the composition and diversity of gut microbiota in individuals diagnosed with obesity. The gut microbiota participate in energy metabolism, lipid synthesis, and regulation of inflammation and therefore play a key role in the pathogenesis of obesity. Therapeutic approaches based on the use of probiotics, prebiotics, Akkermansia muciniphila, and fecal microbiota transplantation have shown promise in animal studies as useful strategies against obesity and metabolic syndrome. However, further research is warranted to conclusively establish the specific strains, dosages, and mechanisms underlying the effectiveness of these novel strategies against obesity in humans.}, }
@article {pmid40497058, year = {2025}, author = {Zhang, Q and Gao, Z and Deng, Y and Xu, X and Sun, W and Liu, R and Zhang, T and Sun, X}, title = {Current status and trends in the study of intestinal flora in cognitive disorders: a bibliometric and visual analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1577597}, pmid = {40497058}, issn = {1664-302X}, abstract = {BACKGROUND: Cognitive impairment is a decline in people's ability to think, learn, and remember, which has some impact on an individual's daily activities or social functioning. Microbial toxins and metabolites from dysregulated gut microbiota directly interact with the intestinal epithelium. This interaction triggers neuroinflammation and neurodegeneration in the central nervous system, ultimately impairing cognitive function. It has been found that modulation of gut flora can be an effective intervention to improve cognitive dysfunction. This study is the first to summarize and outline the global research status and trends in this field from a bibliometric perspective, providing reference and guidance for future research in this field.<br><br>METHODS: Based on the Web of Science Core Collection (WoSCC) database, Literature on gut flora and cognitive impairment published between 1999-2025 was searched. Bibliometric analysis was performed using VOSviewer and CiteSpace software to analyze the data on countries, institutions, authors, journals, keywords, citations, and to generate visual maps.<br><br>RESULTS: A total of 1,702 pieces of related literature were retrieved. The overall trend of publication is increasing. China has published the largest number of papers, and Huazhong University of Science &amp; Technology and Kim, Dong-Hyun were the institutions and individuals with more publications. The most frequently cited journal is SCI REP-UK. The most frequent keywords are gut microbiota, followed by Alzheimer's disease, cognitive impairment, Brain, oxidative stress and Inflammation.<br><br>CONCLUSION: In recent years, the research application of gut flora in the treatment of cognitive impairment has made remarkable progress. Oxidative stress and inflammatory response have become the main research hotspots for gut flora to improve cognitive impairment in patients. The gut-brain axis plays an important role in the study of the mechanism of action. Short-chain fatty acids are the focus of research on gut microbial metabolism. Fecal microbial transplantation technology is increasingly being used as an emerging method for the application of intestinal flora. Modifying the gut flora by modifying diet and exercise may be an effective strategy to prevent and improve cognitive dysfunction in the future. Future studies may focus more on gender differences in the role of gut flora in the modulation of cognitive function.}, }
@article {pmid40497049, year = {2025}, author = {Ren, X and Zheng, L and Huang, L and Zhao, J}, title = {The role of the gut microbiota in shaping the tumor microenvironment and immunotherapy of breast cancer.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1591745}, pmid = {40497049}, issn = {1664-302X}, abstract = {Breast cancer is the most prevalent malignancy among women worldwide and is a major contributor to cancer-related mortality. The tumor microenvironment (TME), composed of tumor cells, immune infiltrates, fibroblasts, and vascular components, is critically involved in tumor initiation, metastatic progression, and therapeutic response. In recent years, therapies targeting the TME have undergone rapid advancements, with the objective of enhancing antitumor immunity. Concurrently, mounting evidence underscores the pivotal role of the gut microbiota and its metabolites in modulating host immunity, influencing metabolic homeostasis, inflammation, and immune equilibrium. The composition and diversity of the gut microbiome influence breast cancer progression and patients' responses to immunotherapy. Therefore, modulating the gut microbiota is a promising strategy to enhance the clinical outcomes of TME-targeted immunotherapies. In this review, we discuss the influence of gut microbiota and its derived metabolites on breast cancer progression and immunotherapy prognosis and explore potential strategies to optimize immunotherapy through gut microbiota modulation.}, }
@article {pmid40497047, year = {2025}, author = {Rivero, MR and Vissio, C and Feliziani, C and De Angelo, C and Touz, MC and Tiranti, K and Lombardelli, JA and Duartez, FJ and Curletto, L}, title = {Cryptosporidium spp. in Argentina: epidemiology and research advances in human, animal, and environmental settings during the 21st century.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1592564}, pmid = {40497047}, issn = {1664-302X}, abstract = {INTRODUCTION: Cryptosporidium spp. is an intestinal protozoan causing cryptosporidiosis, a diarrheal disease affecting humans and animals, with zoonotic potential. In immunocompromised individuals, infections can be severe or fatal. It is a major waterborne parasite and a leading cause of neonatal diarrhea in calves. This study systematically reviews Cryptosporidium spp. research in Argentina during the 21st century, highlighting its epidemiological significance and research gaps.<br><br>METHODS: A systematic review following PRISMA guidelines was conducted using LILACS, PubMed, Scopus, and SciELO Argentina. Eligible studies (2001-2024) included human (community and hospital-based), animal (domestic, wild, and captive), and environmental (water, soil and vegetable) surveys. The review analyzed epidemiology, diagnosis, treatment, genetic diversity, distribution, and risk factors.<br><br>RESULTS: Of 277 articles reviewed, 66 met eligibility criteria. Cryptosporidium spp. was detected in 17 of Argentina's 23 provinces, mainly in the Pampean region. Five species were identified (C. hominis, C. parvum, C. suis, C. scrofarum, and C. varanii), though genetic diversity studies remain limited. Human cryptosporidiosis primarily affects immunocompromised individuals (HIV/AIDS, transplant recipients, hematologic cancer patients). The parasite was found in feces, duodenal biopsies, blood, sputum, and cerebrospinal fluid, with complications such as cholangiopathy and pulmonary cryptosporidiosis. Infections with C. hominis and C. parvum (including co-infections) were observed, with multiple subtypes documented. In animals, C. parvum was prevalent in Pampean calves, while C. suis and C. scrofarum were found in domestic pigs. Wildlife, including non-human primates and coypu, also tested positive. Cryptosporidium was detected in recreational and drinking water samples. No Cryptosporidium spp. oocysts were detected in soil. Risk factors included socio-economic conditions and animal management practices.<br><br>CONCLUSION: Cryptosporidium spp. is widely distributed in Argentina, yet eco-epidemiological transmission factors remain poorly understood, hindering control strategies. Limited research on genetic diversity and distribution highlights the need for further studies, particularly in vulnerable populations and areas of close human-animal interaction, such as productive systems. The presence of Cryptosporidium spp. in water underscores the importance of improving public health policies and water treatment standards. From a One Health perspective, these findings emphasize the need for enhanced epidemiological surveillance and research to strengthen prevention and control in Argentina.}, }
@article {pmid40495848, year = {2025}, author = {Iqbal, A and Bokhari, SFH and Rehman, MU and Faizan Sattar, SM and Bakht, D and Dost, W and Basit, A}, title = {Gut-brain connection in schizophrenia: A narrative review.}, journal = {World journal of psychiatry}, volume = {15}, number = {5}, pages = {103751}, pmid = {40495848}, issn = {2220-3206}, abstract = {Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive, emotional, and behavioral impairments. The microbiota-gut-brain axis is crucial in its pathophysiology, mediating communication between the gut and brain through neural, immune, endocrine, and metabolic pathways. Dysbiosis, or an imbalance in gut microbiota, is linked to neuroinflammation, systemic inflammation, and neurotransmitter disruptions, all of which contribute to the symptoms of schizophrenia. Gut microbiota-derived metabolites, such as short-chain fatty acids, influence brain function, including immune responses and neurotransmitter synthesis. These findings suggest that microbial imbalances exacerbate schizophrenia, providing a novel perspective on the disorder's underlying mechanisms. Emerging microbiota-targeted therapies-such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation-show promise as adjunctive treatments, aiming to restore microbial balance and improve clinical outcomes. While further research is needed, targeting the microbiota-gut-brain axis offers an innovative approach to schizophrenia management, with the potential to enhance patient outcomes and quality of life.}, }
@article {pmid40495179, year = {2025}, author = {Liu, W and Zhou, X and Xiao, L and Huang, X and Chang, D and Zhong, X and Zeng, M and Xian, Y and Zheng, Y and Huang, W and Huang, R and Huang, M}, title = {The gut microbiota-mediated ferroptosis pathway: a key mechanism of ginsenoside Rd against metabolism-associated fatty liver disease.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {83}, pmid = {40495179}, issn = {1749-8546}, support = {2022YFC3501200//National Key Research and Development Program of China/ ; 82274080//National Natural Science Foundation of China Projects/ ; X2024019//School Management Project of Fujian University of Traditional Chinese Medicine/ ; X2024035//School Management Project of Fujian University of Traditional Chinese Medicine/ ; 2024Y9511//Fujian Provincial Science and Technology Innovation Joint Fund Project/ ; }, abstract = {BACKGROUND: Ginsenoside Rd (G-Rd), found in Panax species, has shown therapeutic potential against metabolism-associated fatty liver disease (MAFLD), but its mechanism has not been well elucidated. This study investigated the key mechanisms of G-Rd in modulating the gut microbiome and lipid peroxidation-mediated ferroptosis pathway in MAFLD.<br><br>METHODS: A high-fat diet-induced MAFLD model was established. Ultrastructural changes in liver tissue were observed using transmission electron microscopy. Metagenomics were employed to detect alterations in gut microbiota and their metabolites. Biochemical analysis and immunohistochemistry were used to examine liver injury, blood lipids, lipid peroxidation-related indicators, and tissue iron content.<br><br>RESULTS: G-Rd significantly reduced liver injury and steatosis in MAFLD mice and downregulated the elevated relative abundance of Firmicutes and the Firmicutes/Bacteroidetes ratio. It also significantly reduced the abundances of Faecalibaculum rodentium while increasing Muribaculum intestinale, with its functional role being relevant to lipid metabolism regulation. Moreover, G-Rd ameliorated mitochondrial damage and inhibited the ferroptosis pathway in the liver, which was associated with antioxidant-related factors mediated by Nrf2 signaling. The liver protective effect of G-Rd was driven by the regulation of gut microbiota, as demonstrated by antibiotic cocktail treatment and fecal microbiota transplantation.<br><br>CONCLUSIONS: G-Rd attenuated HFD-induced MAFLD by alleviating liver oxidative stress, lipid peroxidation, and ferroptosis through modulation of the gut microbiota. The antioxidant and anti-ferroptotic actions of G-Rd, mediated via the Nrf2 pathway, were found to contribute to the amelioration of liver injury and hepatic steatosis in MAFLD.}, }
@article {pmid40494686, year = {2025}, author = {von Muhlenbrock, C and Núñez, P and Herrera, K and Pacheco, N and Quera, R}, title = {Fecal microbiota transplantation through colonoscopy for the management of severe refractory irritable bowel syndrome: Preliminary results.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.rgmxen.2025.03.001}, pmid = {40494686}, issn = {2255-534X}, abstract = {Recent studies have explored the role of the microbiota in disorders of gut-brain interaction, opening pathways for therapies, such as dietary adjustments, probiotics, and fecal microbiota transplantation (FMT). We present herein a pilot study on 4 patients with severe irritable bowel syndrome (IBS), refractory to conventional treatment, in which FMT through colonoscopy showed improvement in pain, bloating, and stool consistency that was maintained during the 6-month follow-up. To establish the broader clinical application of FMT, more research on its efficacy according to instillation site and patient results is needed.}, }
@article {pmid40494661, year = {2025}, author = {Laura, R and Fariha, B and Claire, R and Christopher, B and Lewindon, P}, title = {Oral vancomycin solution is superior to capsule in inducing clinical biomarker and endoscopic remission in children with atypical ulcerative colitis.}, journal = {British journal of clinical pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1002/bcp.70121}, pmid = {40494661}, issn = {1365-2125}, support = {240050//Lastentautien Tutkimuss&#xe4;&#xe4;ti&#xf6;/ ; //Orionin Tutkimuss&#xe4;&#xe4;ti&#xf6;/ ; T63344/50621//State funding for university-level health research, Tampere University Hospital, Wellbeing services county of Pirkanmaa/ ; }, abstract = {AIMS: Atypical colitis (presenting reverse gradient colitis, backwash ileitis or rectal sparing) is associated with primary sclerosing cholangitis-ulcerative colitis (PSC). Oral vancomycin has been used to manage paediatric atypical colitis with/without confirmed PSC. Different preparations had shown different efficacy. We compared oral vancomycin solution to capsules in inducing remission in children with atypical colitis, while assessing other potential confounders.<br><br>METHODS: Children using oral vancomycin for at least 3&#x2009;months to manage atypical colitis were retrospectively identified. Factors associated with colitis remission (Paediatric Ulcerative Colitis Activity Index [PUCAI], faecal calprotectin, colonoscopy and histology) were explored.<br><br>RESULTS: Of 32/48 children with elevated PUCAI, 27/32 achieved PUCAI&#x2009;<&#xa0;10 (20/23 after solution vs. 7/9 after capsules, P&#x2009;=&#xa0;.520). Faecal calprotectin <100&#x2009;&#x3bc;g/g was achieved in 35/48 (28/35 after solution vs. 6/13 after capsules, P&#x2009;=&#xa0;.022). Follow-up colonoscopy during treatment (n&#x2009;=&#xa0;25) showed reduced Mayo from median 2 to 0 (P&#x2009;<&#xa0;.001) after solution vs. from 2 to 1 (P&#x2009;=&#xa0;.257) after capsules. Pan-colonic histological remission was seen in 14/25 (12/20 after solution vs. 1/5 after capsules, P&#x2009;=&#xa0;.109). In adjusted analysis, use of oral vancomycin solution was a significant predictor for biomarker (adjusted odds ratio 23.1, 95% confidence interval 2.11-253) and pan-colonic histological remission (adjusted odds ratio 900, 95% confidence interval 1.61-504&#x2009;929). No other predictors were identified. Within 12&#x2009;months after ceasing oral vancomycin in children who achieved remission, 52% relapsed. No clinical predictors, including vancomycin preparation, were established.<br><br>CONCLUSION: Oral vancomycin solution was superior to capsules for inducing biomarker and colonoscopic remission in children with atypical colitis with/without confirmed PSC. This finding warrants further investigation to ensure optimal use.}, }
@article {pmid40491765, year = {2025}, author = {Tang, Y and Xie, X and Guo, Y and Chen, Y and Huang, X and Dai, D and Wu, X}, title = {Exploring correlation between preoperative gut microbiota and PONV using 16S absolute quantitative sequencing: a prospective observational study.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1563329}, pmid = {40491765}, issn = {2296-858X}, abstract = {BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complication following surgery. Despite various preventive measures, satisfactory outcomes have not been achieved. This study explores the potential of gut microbiota interactions with the host in understanding and preventing PONV, using 16S absolute quantitative sequencing technology to uncover new insights.<br><br>METHODS: Patients who experienced nausea and vomiting within 24&#x202f;h after surgery were divided into a PONV group (n&#x202f;=&#x202f;22) and a non-PONV group (n&#x202f;=&#x202f;22). Microbial communities linked to PONV were assessed through bioinformatics analysis. Fecal samples from both groups were transplanted into rats, which were then anesthetized with isoflurane for 100&#x202f;min. Pica behavior was monitored over the next 24&#x202f;h to assess nausea and vomiting in the rats.<br><br>RESULTS: Significant differences in &#x3b1;- and &#x3b2;-diversity were observed between the PONV and non-PONV groups. Six key microorganisms were identified, with Bifidobacterium, Bilophila, and Oscillibacter showing a negative correlation with PONV severity. Receiver operating characteristic (ROC) analysis demonstrated that Bifidobacterium could reliably predict PONV. Rats receiving feces from the PONV group exhibited significantly higher kaolin consumption within 24&#x202f;h post-anesthesia compared to those receiving feces from the non-PONV group.<br><br>CONCLUSION: These results suggest a potential new mechanism for PONV involving gut microbiota, offering a theoretical basis for preoperative prediction of PONV based on gut microbial composition.}, }
@article {pmid40491530, year = {2025}, author = {Jian, S and Jian, X and Ye, L and Yang, K and Zhang, L and Xie, Y and Deng, J and Yin, Y and Deng, B}, title = {Gallic acid prevents obesity in mice on a high-fat diet via the gut microbiota-adipose tissue axis.}, journal = {Current research in food science}, volume = {10}, number = {}, pages = {101084}, pmid = {40491530}, issn = {2665-9271}, abstract = {Obesity is closely related to the gut microbiota, and gallic acid (GA) has anti-obesity properties, but its relationship with the gut microbiota is unclear. The aim of this study was to investigate the role of gut microbiota in the anti-obesity mechanism of GA by fecal microbiota transplantation (FMT). Here, we found that high-fat diet (HFD) promoted lipid deposition and gut microbiota dysbiosis in mice, whereas GA slowed down lipid deposition and restored gut microbiota dysbiosis and its functional profile, as evidenced by the reduction of the obesity-causing bacterium Desulfovibrio and the enrichment of the beneficial bacterium Lachnospiraceae_NK4A136_group, Clostridiales_unclassified, Oscillospira and Adlercreutzia. These gut microbiota and metabolites produced positive feedback effects on body weight, glucose tolerance, insulin resistance, as well as glycemic and lipid parameters. Mechanistically, GA significantly enhanced lipid and energy metabolism in obese mice by promoting the expression of uncoupling protein 1 (UCP1), adiponectin, and adiponectin receptor 2 in white adipose tissue of the epididymal white adipose tissue, as well as promoting thermogenesis in interscapular brown adipose tissue by stimulating UCP1 expression. Interestingly, GA failed to alleviate lipid accumulation in HFD of antibiotic-treated mice. In contrast, after FMT treatment, the fecal microbiota of GA-treated donor mice significantly alleviated lipid metabolism in HFD-fed mice, which is mechanistically consistent with direct addition of GA. Collectively, GA can alleviate HFD-induced obesity by modulating the gut microbiota, and the specific mechanism may be through the gut microbiota-adipose tissue axis.}, }
@article {pmid40488649, year = {2025}, author = {Park, JH and Lee, YK and Lee, CK and Lee, HS and Kim, JH and Lee, MH and Seo, YJ and Cho, H and Park, CS}, title = {The preventive effect of solubilized sturgeon oil on dextran sulfate sodium-induced ulcerative colitis via inflammation attenuation and intestinal microbiota regulation.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo01038a}, pmid = {40488649}, issn = {2042-650X}, abstract = {Ulcerative colitis (UC), an inflammatory bowel disease, causes inflammation in the colonic mucosa. The pathogenesis of UC is closely linked to abnormalities in the gastrointestinal microbiota and immune response. Current treatments for UC primarily alleviate symptoms but are associated with several drawbacks, particularly with prolonged use. Therefore, there is a crucial need to explore novel treatment strategies. Solubilized sturgeon oil (SSO) has gained prominence for its anti-inflammatory effects in various contexts; however, its efficacy in UC has not yet been investigated. In this study, we investigated the preventive effects and underlying mechanisms of SSO in a dextran sulfate sodium-induced UC model. Oral administration of SSO significantly alleviated colitis severity by improving weight, disease activity index, and colon length. Moreover, SSO significantly downregulated the expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha, cyclooxygenase-2, and nitric oxide synthase, while enhancing the expression of tight junction-related proteins such as occludin and ZO-1 in colonic tissues. Additionally, SSO inhibited the activation of lipopolysaccharide-stimulated dendritic cells and macrophages and induced alterations in the gut microbiota, with increased Firmicutes and decreased Bacteroidetes abundances. Furthermore, colitis and gastrointestinal inflammation were alleviated in recipient mice that received fecal transplants from SSO-treated mice. These findings indicate that SSO is a promising natural therapeutic agent for preventing colitis by regulating the gastrointestinal microbiota and suppressing the hyperactivation of myeloid cells.}, }
@article {pmid40487274, year = {2025}, author = {Roy, K and Moncada, E and Reddivari, L}, title = {Ulcerative Colitis but Not Dextran Sodium Sulfate-Induced Colitis-Associated Microbiota Promotes Early Biomarkers of Colitis in Interleukin-10 -/- Mice.}, journal = {Gastro hep advances}, volume = {4}, number = {6}, pages = {100636}, pmid = {40487274}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis (UC), are inflammatory gastrointestinal conditions in which the pathogenesis is influenced by immune dysfunction, genetics, and environmental factors. Of the 2 conditions, UC is more prevalent, and there is a positive correlation between bacterial dysbiosis and colitis severity and incidence. Therefore, we hypothesize that mice that are genetically predisposed to colitis when colonized with colitic associated bacteria will exhibit an early onset of colitis biomarkers.<br><br>METHODS: Four sets of germ-free interleukin-10 -/- mice were gavaged orally with pooled fecal samples from 2 healthy individuals or an individual with severe colitis or healthy mice or dextran sodium sulfate (DSS)-induced colitis mice. The disease activity index was used to rank colitis severity weekly in transplanted mice for eight weeks.<br><br>RESULTS: There were significant differences in alpha (Shannon Index) and beta diversity (Bray-Curtis) between healthy and colitic-associated microbiota recipients, indicating dysbiosis (human fecal microbial transplantation P = 8.09&#x2217;10[-6], P = .001); (Mice fecal microbiota transplant P = .0197, P = .025). Despite the lack of colitis development, UC-associated microbiota recipients had reduced mucus thickness and increased expression of proinflammatory cytokines in the distal colon compared to healthy-associated microbiota recipients. However, DSS-induced colitis associated microbiota recipients did not show an increase in colitis biomarkers compared to healthy associated microbiota recipients.<br><br>CONCLUSION: This study demonstrates that UC-associated bacterial dysbiosis induces colonic inflammation and mucus thinning, biomarkers of early colitis onset, in interleukin-10 -/- mice compared to mice with healthy human associated bacteria.Colitis induction depends on bacterial community stability as DSS-induced colitis associated microbiota recipients did not show an increase in colitis or colitis biomarkers in the absence of DSS.}, }
@article {pmid40486846, year = {2025}, author = {Shang, M and Ning, J and Zang, C and Ma, J and Yang, Y and Wan, Z and Zhao, J and Jiang, Y and Chen, Q and Dong, Y and Wang, J and Li, F and Bao, X and Zhang, D}, title = {Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis via suppressing IL-13Rα1 related signaling pathways.}, journal = {Acta pharmaceutica Sinica. B}, volume = {15}, number = {4}, pages = {2024-2038}, pmid = {40486846}, issn = {2211-3835}, abstract = {Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.}, }
@article {pmid40486731, year = {2025}, author = {Zhou, C and Feng, X and Liu, H and Cai, T and Li, Y and Fan, H}, title = {Bidirectional modulation of Alzheimer's disease via gut microbiota: rescue by fecal transplantation from healthy donors and aggravation by colitis-associated dysbiosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1593854}, pmid = {40486731}, issn = {1662-4548}, abstract = {INTRODUCTION: Emerging evidence implicates gut microbiota dysbiosis as a key modulator for the pathogenesis of Alzheimer's disease (AD) via the gut-brain axis. To investigate the causal role of microbial communities in AD progression, we performed fecal microbiota transplantation (FMT) in APP/PS1 transgenic mice using donor microbiota from healthy wild-type mice or dextran sulfate sodium (DSS)-induced colitis mice.<br><br>METHODS: Cognitive function, amyloid-beta (A&#x3b2;) pathology, and pro-inflammatory cytokine levels were assessed in mice. 16S ribosomal RNA sequencing of gut microbiota and bioinformatic functional analyses were applied to identify the specific microbial communities potentially involved in AD progression.<br><br>RESULTS: FMT-WT mice (fecal microbiota transplantation from healthy wild-type mice) exhibited significant improvements in spatial memory (Morris Water Maze), exploratory behavior (Y-maze), and locomotor activity (Open Field Test), alongside reduced A&#x3b2; plaque burden and normalized expression of pro-inflammatory cytokines (IL-6, IL-1&#x3b2;, TNF-&#x3b1;) in both gut and brain tissues. Conversely, FMT-DSS mice (fecal microbiota transplantation from DSS-treated donors) displayed exacerbated cognitive deficits, heightened A&#x3b2; deposition, and elevated pro-inflammatory cytokine levels. Microbial profiling revealed stark contrasts: FMT-WT mice harbored beneficial taxa (Bacteroides, Lachnospiraceae) linked to anti-inflammatory products like short-chain fatty acid, while FMT-DSS mice showed blooms of pathogenic genera (Erysipelatoclostridium, Enterobacteriaceae) associated with neurotoxic metabolites. Functional analyses predicted enrichment of neuroprotective pathways (e.g., lysine metabolism) in FMT-WT and pro-inflammatory pathways (e.g., carbon metabolism) in FMT-DSS. Crucially, neuroinflammation occurred independently of gut barrier disruption, implicating circulating microbial metabolites as key mediators.<br><br>DISCUSSION: Our findings demonstrate that gut microbiota composition bidirectionally influences AD progression, with FMT from healthy donors attenuating neuroinflammation and pathology, while colitis-associated dysbiosis exacerbates disease hallmarks. Our study positions microbiota-targeted therapies as a promising strategy to modulate AD progression through the gut-brain axis.}, }
@article {pmid40485937, year = {2025}, author = {Liu, Y and Zhang, P and Sun, H}, title = {A narrative review of research advances in gut microbiota and microecological agents in children with attention deficit hyperactivity disorder (ADHD).}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1588135}, pmid = {40485937}, issn = {1664-0640}, abstract = {The role of gut microecology in attention deficit hyperactivity disorder (ADHD) has garnered growing attention. Studies have suggested a potential link between ADHD development and an imbalance in gut microbiota composition. This review aims to analyze the characteristics of the gut microbiota in children with ADHD, explore how changes in the gut microbiota affect ADHD through nervous, neuroendocrine, and immune pathways, and discuss the potential application of microecological agents and fecal microbiota transplantation in the prevention and treatment of ADHD in children. Pubmed, Google Scholar, EBSCO, Scopus and Medline were utilized to conduct searches using the following key terms:Attention Deficit Hyperactivity Disorder OR ADHD AND gut microbiota OR probiotics OR prebiotics OR synbiotics OR fecal microbiota transplantation OR FMT. Studies published in English from all years were included. A thorough review of numerous papers and their references was conducted to identify relevant articles. Sorting and analysis revealed that the gut microbiota of children with ADHD has changed to some extent, and targeting the gut microbiota, using microecological agents or fecal microbiota transplantation, especially in combination with central nervous system stimulants, may provide additional benefits for children with ADHD.}, }
@article {pmid40485663, year = {2025}, author = {Radford-Smith, DE and Oke, K and Costa, CFFA and Anthony, DC}, title = {Systematic review and meta-analysis of microbiota-gut-astrocyte axis perturbation in neurodegeneration, brain injury, and mood disorders.}, journal = {Brain, behavior, &amp; immunity - health}, volume = {46}, number = {}, pages = {101013}, pmid = {40485663}, issn = {2666-3546}, abstract = {BACKGROUND: Astrocytes are essential for preserving homeostasis, maintaining the blood-brain barrier, and they are a key element of the tripartite neuronal synapse. Despite such multifaceted roles, their importance as contributors to the microbiota-gut-brain axis studies, which typically focus on microglia and neurons, has been largely overlooked. This meta-analysis provides the first systematic review of the microbiota-gut-astrocyte (MGA) axis in vivo, integrating findings across distinct neurological diseases.<br><br>METHODS: A systematic narrative review was conducted per PRISMA guidelines. The search term employed for PubMed was "Microbiota"[MeSH] AND (astrocyte OR glial) NOT (Review[Publication Type]) and for Web of Science, Embase, and Scopus, "Microbio&#x2217; AND (astrocyte OR glial)" with filters applied to exclude review articles. Searches were completed by May 9th[,] 2024. Data extracted included study models, interventions, and outcomes related to astrocyte biology and rodent behaviour. SYRCLE's risk of bias tool was used to assess individual study designs.<br><br>RESULTS: 53 studies met the inclusion criteria, covering rodent models of stroke and traumatic (acute) brain injury, chronic neurodegenerative diseases including Alzheimer's and Parkinson's disease and other heterogeneous models of cognitive impairment and affective disorders. Significant heterogeneity in methodology was observed between studies. Five studies had a high risk of bias, and 15 were low risk. Astrocyte biology, typically measured by GFAP expression, was increased in neurodegeneration and acute brain injury models but varied significantly in mood disorder models, depending on the source of stress. Common findings across diseases included altered gut microbiota, particularly an increased Bacteroidetes/Firmicutes ratio and compromised gut barrier integrity, linked to increased GFAP expression. Faecal microbiota transplants and microbial metabolite analyses suggested a direct impact of the gut microbiota on astrocyte biology and markers of neuroinflammation.<br><br>CONCLUSIONS: This review and meta-analysis describes the impact of the gut microbiota on astrocyte biology, and argues that the MGA axis is a promising therapeutic target for neurological disorders. However, it is clear that our understanding of the relationship between the gut microbiota and astrocyte behaviour is incomplete, including how different subtypes of astrocytes may be affected. Future studies must adopt new, multi-dimensional studies of astrocyte function and dysfunction, to elucidate their role in disease and explore the therapeutic potential of gut microbiota modulation.}, }
@article {pmid40484955, year = {2025}, author = {Lin, A and Huang, L and Jiang, A and Zhu, L and Mou, W and Li, Y and Zhang, C and Liu, Z and Zhang, J and Cheng, Q and Wei, T and Luo, P}, title = {Microbiota boost immunotherapy? A meta-analysis dives into fecal microbiota transplantation and immune checkpoint inhibitors.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {341}, pmid = {40484955}, issn = {1741-7015}, support = {2021A1515012593//Natural Science Foundation of Guangdong Province/ ; 82373129//National Natural Science Foundation of China/ ; 82172750//National Natural Science Foundation of China/ ; 2022A1515111212//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2023A04J1257//Science and Technology Program of Guangzhou/ ; NO.2023RC3074//Hunan Youth Science and Technology Talent Project/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; *Neoplasms/therapy ; *Gastrointestinal Microbiome ; *Immunotherapy/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) are a cornerstone of modern cancer treatment, but their effectiveness is limited. Fecal microbiota transplantation (FMT), which alters the gut microbiome, has shown promise in enhancing ICIs' therapeutic effects.<br><br>METHODS: We conducted a comprehensive search of relevant studies available up to September 30, 2024, to analyze the clinical efficacy and safety of combining FMT with ICIs in cancer treatment. The primary endpoint was the objective response rate (ORR), with secondary evaluations of survival outcomes and safety.<br><br>RESULTS: A total of 10 studies involving 164 patients with solid tumors were included. The pooled ORR was 43% (95% CI: 0.35-0.51). Subgroup analysis revealed that the combination of anti-PD-1 and anti-CTLA-4 therapies was associated with a significantly higher ORR (60%) compared to anti-PD-1 monotherapy (37%; P&#x2009;=&#x2009;0.01). The incidence of grade 1-2 adverse events (AEs) was 42% (95% CI: 0.32-0.52), while grade 3-4 AEs occurred in 37% of patients (95% CI: 0.28-0.46).<br><br>CONCLUSIONS: This meta-analysis provides preliminary evidence supporting the use of FMT as a strategy to enhance the efficacy of ICIs in patients with advanced or refractory solid tumors. However, larger-scale randomized controlled trials with long-term follow-up are required to confirm and optimize treatment protocols.}, }
@article {pmid40484558, year = {2025}, author = {Liu, W and Yu, L and Chen, Q and Zhang, C and Wang, L and Yu, N and Peng, D and Ou, J and Chen, W and Zhang, Y and Wang, Y}, title = {Poria cocos polysaccharides alleviate obesity-related adipose tissue insulin resistance via gut microbiota-derived short-chain fatty acids activation of FGF21/PI3K/AKT signaling.}, journal = {Food research international (Ottawa, Ont.)}, volume = {215}, number = {}, pages = {116671}, doi = {10.1016/j.foodres.2025.116671}, pmid = {40484558}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Insulin Resistance ; *Obesity/metabolism ; *Polysaccharides/pharmacology ; Mice ; Proto-Oncogene Proteins c-akt/metabolism ; Male ; *Fatty Acids, Volatile/metabolism ; Fibroblast Growth Factors/metabolism ; Signal Transduction/drug effects ; Diet, High-Fat/adverse effects ; *Adipose Tissue/metabolism/drug effects ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/metabolism ; *Wolfiporia/chemistry ; }, abstract = {Obesity is a chronic condition that increases the risk of metabolic disorders, with intestinal dysbiosis and adipose tissue insulin resistance (Adipose-IR) playing key roles in its pathogenesis. Poria cocos polysaccharides (PCP), derived from traditional Chinese medicine, have shown potential in improving glucose metabolism and modulating gut microbiota. However, whether PCP can alleviate obesity-induced Adipose-IR and its dependence on gut microbiota remain unclear. This study investigated the effects of PCP on Adipose-IR in high-fat diet (HFD)-induced obese mice. PCP supplementation reduced body weight, adipose tissue mass, and improved glucose tolerance and lipid metabolism. Histological analysis showed alleviation of adipocyte hypertrophy and colonic barrier damage. PCP also modulated gut microbiota, enhancing the abundance of Lactobacillus, Allobaculum, and Phascolarctobacterium, and increased fecal short-chain fatty acids (SCFAs). These changes activated fibroblast growth factor 21 (FGF21), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and glucose transporter 4 (GLUT4) expression, improving insulin sensitivity. Antibiotic treatment and fecal microbiota transplantation (FMT) further confirmed that PCP's effects on glucose and lipid metabolism are gut microbiota-dependent. Our findings suggest that PCP may serve as a prebiotic agent to alleviate obesity-induced Adipose-IR and metabolic disorders, supporting its potential for functional food development.}, }
@article {pmid40482880, year = {2025}, author = {Conrad, MA and Kaplan, AL and Weinbrom, S and Nastasio, S and Jo, D and Conover, K and Lo, K and Liu, E and Crawford, M and Michail, S and Nicholson, M and Hourigan, SK and Kelsen, JR and Kahn, SA}, title = {Fidaxomicin Treatment of Clostridioides difficile Infections and Recurrences in Children and Adolescents: A Retrospective Multicenter Study.}, journal = {The Journal of pediatrics}, volume = {}, number = {}, pages = {114681}, doi = {10.1016/j.jpeds.2025.114681}, pmid = {40482880}, issn = {1097-6833}, abstract = {OBJECTIVE: To report the effectiveness and tolerability of treating children with primary and recurrent Clostridioides difficile infection (CDI) with fidaxomicin in a real-world, multicenter cohort.<br><br>STUDY DESIGN: We performed a multicenter, retrospective, observational study of fidaxomicin treatment for primary or recurrent CDI (rCDI) in children ages 12 months to 18 years old identified from 2013 to 2021 at 5 centers via electronic medical records. Outcomes included assessment of clinical response at day 14 after initiation of fidaxomicin treatment and clinical and microbiologic outcomes at day 60 after initiation of fidaxomicin treatment in the initial responders.<br><br>RESULTS: Of the 95 patients included in this study, 84 (88.4%) were treated with fidaxomicin for a rCDI, and 82 (86.3%) had at least one medical or surgical comorbidity. At the completion of fidaxomicin treatment (ie, by day 14 after initiation), 50 patients (52.6%) had a clinical cure and an additional 29 (30.5%) had improvement of symptoms. Among 79 patients who responded to fidaxomicin treatment, 17 (21.5%) had a clinical and microbiologically confirmed recurrence of CDI by day 60, likely representing relapse. Patients with inflammatory bowel disease (IBD) were less likely to achieve clinical cure at day 14 (OR 0.27 (95% CI 0.11, 0.70)), but 20 patients with IBD who had initial clinical cure or response did not have a demonstrable increased risk of recurrence at day 60. The most common adverse events reported during therapy were abdominal pain and nausea.<br><br>CONCLUSIONS: In this retrospective, real-world study, fidaxomicin for children with CDI appears to be well tolerated and is associated with low rates of treatment failure.}, }
@article {pmid40482640, year = {2025}, author = {DeLeon, O and Mocanu, M and Tan, A and Sidebottom, AM and Koval, J and Ceccato, HD and Kralicek, S and Colgan, JJ and St George, MM and Lake, JM and Cooper, M and Xu, J and Moore, J and Su, Q and Xu, Z and Ng, SC and Chan, FKL and Tun, HM and Cham, CM and Liu, CY and Rubin, DT and Martinez-Guryn, K and Chang, EB}, title = {Microbiome mismatches from microbiota transplants lead to persistent off-target metabolic and immunomodulatory effects.}, journal = {Cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cell.2025.05.014}, pmid = {40482640}, issn = {1097-4172}, abstract = {Fecal microbiota transplant (FMT) is an increasingly used intervention, but its suitability to restore regional gut microbiota, particularly in the small bowel (SB), must be questioned because of its predominant anaerobic composition. In human subjects receiving FMT by upper endoscopy, duodenal engraftment of anaerobes was observed after 4 weeks. We hypothesized that peroral FMTs create host-microbe mismatches that impact SB homeostasis. To test this, antibiotic-treated specific-pathogen-free (SPF) mice were given jejunal, cecal, or fecal microbiota transplants (JMTs, CMTs, or FMTs, respectively) and studied 1 or 3 months later. JMT and FMT altered regional microbiota membership and function, energy balance, and intestinal and hepatic transcriptomes; JMT favored host metabolic pathways and FMT favored immune pathways. MTs drove regional intestinal identity (Gata4, Gata6, and Satb2) and downstream differentiation markers. RNA sequencing (RNA-seq) of metabolite-exposed human enteroids and duodenal biopsies post-FMT confirmed transcriptional changes in mice. Thus, regional microbial mismatches after FMTs can lead to unintended consequences and require rethinking of microbiome-based interventions.}, }
@article {pmid40481571, year = {2025}, author = {Feng, Y and Zhao, Q and Zhao, Y and Ma, C and Tian, M and Hu, X and Chen, F and Li, D}, title = {Lactobacillus plantarum-derived extracellular vesicles from dietary barley leaf supplementation attenuate Citrobacter rodentium infection and intestinal inflammation.}, journal = {Journal of nanobiotechnology}, volume = {23}, number = {1}, pages = {426}, pmid = {40481571}, issn = {1477-3155}, support = {32371511 and 32001677//the National Natural Science Foundation of China/ ; 2020M680256//the China Postdoctoral Science Foundation/ ; }, mesh = {Animals ; *Citrobacter rodentium ; Mice ; *Enterobacteriaceae Infections/microbiology ; *Extracellular Vesicles/metabolism/chemistry ; *Lactobacillus plantarum/metabolism/chemistry ; *Hordeum/chemistry ; Gastrointestinal Microbiome/drug effects ; Colitis/microbiology ; *Plant Leaves/chemistry ; Mice, Inbred C3H ; *Dietary Supplements ; Male ; Inflammation ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a gastrointestinal inflammatory disorder characterized by disturbed interactions between gut microbiota and host immune response. Barley leaf (BL) is a traditional Chinese herb recorded to have health-promoting effects. However, little is known about the beneficial role of BL against enteric infection-induced intestinal inflammation. Here, we uncover that BL protects against Citrobacter rodentium (C. rodentium)-induced infectious colitis by improving host-microbiota interactions.<br><br>METHODS: C3H/HeN mice were fed a diet with/without BL and infected with C. rodentium. Transcriptome sequencing, anti-CD4 antibody treatment, and flow cytometry were conducted to investigate the mechanisms of T cell immune modulation. The intervention involved administering anti-CD4 antibody at 500&#xa0;&#xb5;g each time for three times before and during C. rodentium infection. Analysis of gut microbiota composition was performed by 16S rRNA gene sequencing on fecal samples. Fecal microbiota transplantation was conducted by administering microbiota from donor group to recipient group via oral gavage to investigate the role of intestinal microbiota in immune modulation.<br><br>RESULTS: BL ameliorated the severity of C. rodentium-induced colitis, and this effect was linked to improved gut homeostasis and enhanced mucosal barrier function. BL enriched the pathways of T helper 1 (Th1)/Th2 and Th17 cell differentiation in the colon, suggesting the involvement of CD4[+] T cells. Consistent with this, anti-CD4 antibody treatment abrogated the effect of BL and flow cytometry analysis revealed that BL mitigated C. rodentium-induced pro-inflammatory Th1 immune response. Moreover, the protective effect of BL was associated with alleviation of gut microbiota dysbiosis and increased abundance of Lactobacillus. Our in vivo studies further revealed that live Lactobacillus plantarum (L. plantarum) administration attenuated the pathogenic effects induced by C. rodentium infection, whereas heat-inactivated L. plantarum did not show the same results. Mechanistically, BL supplementation enriched L. plantarum, which subsequently released nanosized extracellular vesicles (EVs) that serve as a key mediator in alleviating C. rodentium-associated pathology and Th1 cell dysregulation.<br><br>CONCLUSIONS: Our work thus provides evidence for utilizing BL and L. plantarum-derived EVs to manage enteric infection-associated IBD.}, }
@article {pmid40478639, year = {2025}, author = {Bathobakae, L and Bashir, R and Koodirile, A and Villegas, K and Rajab, I and Perez, EW and Cavanagh, Y and El-Sedfy, A and Suh, JS}, title = {Clostridioides difficile enteritis: a targeted review of current literature.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/00365521.2025.2515423}, pmid = {40478639}, issn = {1502-7708}, abstract = {Clostridioides difficile enteritis (CDE) is a rare but clinically significant form of Clostridioides difficile infection (CDI) affecting the small intestine. CDE poses a diagnostic challenge owing to its rarity, complexity, and nonspecific presentation. The current data is retrospective in the form of case reports and conference proceedings. The lack of widespread awareness and limited literature on CDE often result in diagnostic delays, contributing to increased morbidity. This targeted narrative review sought to consolidate the current knowledge on the epidemiology, pathophysiology, clinical presentation, and management of CDE, addressing a critical gap in the existing literature. Electronic databases, including PubMed, Embase, and Web of Science, were searched for published cases from inception to April 2024. The initial search yielded 2,120 articles, which were filtered using study design, English language, and human subjects. After screening for duplicates and excluding irrelevant articles, 44 articles comprising 49 patients were included in the final review. Of the 49 individual cases reviewed, 25 (51%) were male and 24 (49%) were female. The patients' ages ranged from 16 to 91 years, with a mean age of 53.4 years. Abdominal pain and diarrhea were the chief complaints reported in 37/49 (76%) and 35/49 (71%) cases, respectively. About 42/49 (86%) cases were effectively treated with antibiotics, while some cases required fecal microbiota transplantation or surgical exploration. Given its grave course, CDE warrants prompt and appropriate treatment to prevent complications such as fulminant enteritis, compartment syndrome, and bowel perforation.}, }
@article {pmid40478172, year = {2025}, author = {Lasagna, A}, title = {Mitigation strategies for gastrointestinal (GI) immune-related adverse events for patients with solid tumors receiving immunotherapy.}, journal = {Immunotherapy}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/1750743X.2025.2516995}, pmid = {40478172}, issn = {1750-7448}, abstract = {Over the past decade, immunotherapy has revolutionized the treatment algorithm for solid tumors. Immune checkpoint inhibitors (ICIs) demonstrated efficacy against several tumor types, but they can favor the development of immune-related adverse events (irAEs). IrAEs can sometimes be life-threatening. In this review, we will briefly analyze the main gastro-intestinal toxicities and focus on potential strategies for mitigating irAEs, particularly through the modification of gut microbiota (GM) composition. Finally, we will briefly dwell on the potential role of artificial intelligence (AI) in the prediction of irAEs.}, }
@article {pmid40475999, year = {2025}, author = {Hwang, D and Chong, E and Li, Y and Li, Y and Roh, K}, title = {Deciphering the gut microbiome's metabolic code: pathways to bone health and novel therapeutic avenues.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1553655}, pmid = {40475999}, issn = {1664-2392}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Bone and Bones/metabolism ; Animals ; Probiotics/therapeutic use ; *Bone Remodeling/physiology ; *Osteoporosis/metabolism/microbiology/therapy ; Prebiotics ; Fecal Microbiota Transplantation ; Bone Diseases/metabolism/microbiology/therapy ; }, abstract = {The gut microbiome plays an important role in the protection against various systemic diseases. Its metabolic products profoundly influence a wide range of pathophysiological events, including the regulation of bone health. This review discusses the recently established connections between the gut microbiome and bone metabolism, focusing on the impact of microbiome-derived metabolites such as SCFAs, Bile Acids, and tryptophan to the control of bone remodeling and immunoreactions. Recent advances in metagenomics and microbiome profiling have unveiled new exciting therapeutic opportunities, ranging from the use of probiotics, prebiotics, engineered microbes, and to fecal microbiota transplantation. Understanding of the interplay among diet, microbiota, and bone health provides new avenues for tailored interventions aimed at reducing disease risk in osteoporosis and other related disorders. By drawing knowledge from microbiology, metabolism, and bone biology, this review highlights the potential of microbiome-targeted therapies to transform skeletal health and the management of bone diseases.}, }
@article {pmid40472289, year = {2025}, author = {Lim, LWZ and Toh, KY and Cook, AR and Lee, JWJ and Lim, JFY}, title = {Public knowledge, awareness and perception of gut microbiome and faecal microbiota transplantation in Singapore: a survey study.}, journal = {Singapore medical journal}, volume = {}, number = {}, pages = {}, pmid = {40472289}, issn = {2737-5935}, abstract = {INTRODUCTION: Despite the exponential increase in microbiome research, knowledge and beliefs about the gut microbiome and faecal microbiota transplantation (FMT) remain unclear. The aim of this study was to identify the extent of knowledge, awareness and perception among the general public regarding the gut microbiome and FMT.<br><br>METHODS: An online questionnaire on knowledge and beliefs about the gut microbiome and FMT was administered to 1831 participants. Data analysis software was used to generate descriptive statistics and explore associations between knowledge and sociodemographic variables.<br><br>RESULTS: Even though only 33% of participants had heard of the gut microbiome, more than 92% had consumed probiotic drinks or supplements. While 85% had not heard of the FMT procedure, 72% of respondents would consider having FMT to treat Clostridioides difficile infection (CDI). Willingness to receive FMT depended mainly on recommendation from healthcare providers (77%). Knowledge and awareness regarding the gut microbiome and FMT were relatively low, despite most participants having prior gut health-related behaviours.<br><br>CONCLUSION: This study identified the public's perceptions of FMT and the potential barriers to its uptake. Insights from the study highlight the need for health education to enhance acceptance of FMT and the importance of using information supported by medical professionals to immunise the public against poorly validated science.}, }
@article {pmid40471587, year = {2025}, author = {Wei, M and Huang, Q and Yu, F and Luo, YF and Feng, X and Liao, D and Li, J and Zhang, B and Liu, ZY and Xia, J}, title = {Elevated phenylacetylglutamine caused by gut dysbiosis associated with type 2 diabetes increases neutrophil extracellular traps formation and exacerbates brain infarction.}, journal = {Clinical science (London, England : 1979)}, volume = {}, number = {}, pages = {}, doi = {10.1042/CS20242943}, pmid = {40471587}, issn = {1470-8736}, support = {2022YFC3602400, 2022YFC3602401//National Key Research and Development Projects/ ; 82271369; 82301514; 82471365//National Natural Science Foundation of China/ ; 2021JJ31109; 2023JJ41018//Natural Science Foundation of Hunan Province/ ; }, abstract = {Type 2 diabetes (T2D) aggravates ischemic stroke. The association between gut microbiota-derived metabolite phenylacetylglutamine (PAGln) and ischemic stroke patients with T2D remains unclear. Therefore, we aimed to explore the change of gut microbiota and its metabolite, PAGln in ischemic stroke patients with T2D, as well as investigate the role of PAGln in this disease. We performed two clinical cohort studies to investigate the changes of gut microbiota and PAGln in ischemic stroke patients with T2D. Then, we transplanted fecal microbiota from patients into rats and established a middle cerebral artery occlusion model. Finally, an intraperitoneal injection of PAGln was administered to rats to test whether it exacerbates brain infarction. Plasma PAGln levels were significantly higher in stroke patients with T2D compared to those without T2D. There was a positive correlation of Plasma PAGln with NETs. Enterobacteriaceae, Verrucomicrobiota, and Klebsiella were enriched in stroke patients with T2D and showed a significant positive correlation with PAGln levels. The rats transplanted with fecal microbes from stroke patients with T2D developed a more severe brain injury and had higher levels of plasma PAGln and NETs compared to the rats transplanted with fecal microbes from stroke patients without T2D. Additionally, rats treated with PAGln exhibited more severe brain injury accompanied by increased systemic inflammation, oxidative stress and NET formation. Our results suggest elevated circulating PAGln levels, resulting from gut dysbiosis in stroke patients with T2D, may exacerbate brain infarction through NETs formation, systemic inflammation, and oxidative stress.}, }
@article {pmid40470286, year = {2025}, author = {Hetterich, J and Pees, M}, title = {Case Report: Oral fecal microbiota transplantation in a Mediterranean spur-thighed tortoise (Testudo graeca) suffering from chronic gastrointestinal disease-procedure, clinical outcome and follow-up.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1560689}, pmid = {40470286}, issn = {2297-1769}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is the process of transferring fecal microbiota from a healthy donor into the gastrointestinal tract of a recipient. Although many mechanisms of FMT are still not completely understood at present, it has been described that the treatment of various gastrointestinal diseases in different species, including humans, is significantly improved by FMT therapy. Since the first report on FMT therapy in veterinary medicine in small mammals numerous cases have been reported, but little information has been published on the therapeutic effects of FMT treatment in reptiles. The present case report describes the effects of orally administered fecal microbiota transplantation in a Mediterranean spur-thighed tortoise (Testudo graeca) suffering from chronic gastrointestinal disorders.<br><br>CASE PRESENTATION: A nine-year-old, 330&#x202f;g, intact female Mediterranean spur-thighed tortoise (Testudo graeca) from the animal owner's own offspring was presented for consultation due to decreased general condition, anorexia and sialorrhea following oral intake of a lettuce species (Lactuca virosa) known for its poisonous plant ingredients (sesquiterpene lactones) 3&#x202f;weeks prior to presentation. Pre-existing conditions were not reported. Clinical examination revealed sialorrhea and a reduced general condition. Diagnostic procedures included blood chemistry, radiography and ultrasonography. Despite repeated treatment attempts with various medical regimes over 158&#x202f;days, the tortoise continued showing variable recurring gastrointestinal symptoms. An orally administered FMT was initiated and continued for a total of 3&#x202f;weeks. Gastrointestinal signs improved rapidly within 1&#x202f;week and resolved completely after 3&#x202f;weeks. Over a follow up period of 9&#x202f;months, no symptom recurrence or adverse effects were monitored.<br><br>CONCLUSION: This case report describes the first successful trial of fecal microbiota transplantation in chelonians. The outcome indicates that this therapeutic approach may be beneficial not only to small animals but also for the therapy of gastrointestinal disorders in reptiles, especially those cases with insufficient conventional therapy results.}, }
@article {pmid40469520, year = {2025}, author = {Yu, L and Chen, Z and Yin, S and Guo, Q and Chen, Y and Li, J and Wang, Y and Liu, X and Xu, Z and Zhang, Y and Zhang, Y and Zheng, Z and Chen, K and Ding, Y and Fan, H and Liu, Z and Ding, Y}, title = {Gut-derived Lactobacillus from exceptional responders mitigates chemoradiotherapy-induced intestinal injury through methionine-driven epigenetic modulation.}, journal = {iMeta}, volume = {4}, number = {3}, pages = {e70043}, pmid = {40469520}, issn = {2770-596X}, abstract = {Acute chemoradiotherapy-induced intestinal injury (ACRIII) is a common and debilitating complication in patients with colorectal cancer, significantly impairing both quality of life and treatment outcomes. This study aimed to investigate the role of the gut microbiome in mitigating ACRIII. Through bioinformatics analysis of clinical fecal samples and fecal microbiota transplantation (FMT) experiments in mice, we identified a strong association between a high abundance of Lactobacillus species and the absence of ACRIII. From the fecal samples of rectal cancer patients who achieved complete remission without experiencing ACRIII during chemoradiotherapy, 10 novel Lactobacillus strains were isolated and characterized. Among these, Lacticaseibacillus rhamnosus DY801 exhibited a robust capacity to synthesize methionine through metB. This microbial methionine production modulated methionine metabolism in host gut lymphoid tissue inducer (Lti) cells, without diminishing the therapeutic efficacy of chemoradiotherapy. Supplementation with methionine increased intracellular levels of S-adenosylmethionine and enhanced histone H3 lysine 4 trimethylation (H3K4me3) in Lti cells. These epigenetic modifications led to the suppression of pro-inflammatory cytokines interleukin-17A (IL-17A) and interleukin-22 (IL-22), ultimately reducing ACRIII severity. Our findings suggest that specific Lactobacillus strains derived from patients with exceptional treatment responses may offer a novel therapeutic avenue for preventing or alleviating ACRIII. This microbiome-based approach holds significant potential for improving patient outcomes and enhancing the tolerability of chemoradiotherapy in colorectal cancer.}, }
@article {pmid40469517, year = {2025}, author = {Zhang, F and Li, R and Liu, Y and Liang, J and Gong, Y and Xiao, C and Cai, J and Wang, T and You, Q and Zhang, J and Chen, H and Xiao, J and Zhang, Y and Yang, Y and Li, H and Yao, J and Zhang, Q and Zheng, J}, title = {Integrative cross-tissue analysis unveils complement-immunoglobulin augmentation and dysbiosis-related fatty acid metabolic remodeling during mammalian aging.}, journal = {iMeta}, volume = {4}, number = {3}, pages = {e70027}, pmid = {40469517}, issn = {2770-596X}, abstract = {Aging-related decline and adaptation are complex, multifaceted processes that affect various tissues and increase risk of chronic diseases. To characterize key changes in cross-tissue aging, we performed comprehensive proteomic and metabolomic analyses across 21 solid tissues and plasma samples, alongside shotgun metagenomic profiling of fecal microbial communities in young and aged mice. Our findings revealed widespread aging-rewired chronic inflammation, characterized by complement system activation in plasma and universal immunoglobulins accumulation across multiple solid tissues. This inflammatory remodeling significantly enhanced vulnerability to aging-related tissue injury. Moreover, we identified organ-specific and organ-enriched proteins with high functional specificity. Among these, aging-related proteins were closely linked to disorders arising from lipid metabolism dysfunction. Analysis of multi-tissue metabolomic and fecal metagenomic profiles revealed that aging significantly disrupted inter-tissue metabolic coupling, activities of polyunsaturated fatty acids metabolism, and gut microbiota homeostasis. Aged mice exhibited a marked decrease in Escherichia and an increase in Helicobacter, strongly correlating with alterations in omega-3 and omega-6 fatty acid abundances. Through multi-omics integration, we identified key molecular hubs driving organismal responses to aging. Collectively, our study uncovers extensive aging-associated alterations across tissues, emphasizing the interplay between systemic inflammation and dysbiosis-driven fatty acid remodeling. These findings provide deeper insights into the development of healthy aging from a cross-tissue perspective.}, }
@article {pmid40469413, year = {2025}, author = {Shimizu, K and Ogura, H and Oda, J}, title = {Gut dysbiosis and its treatment in patients with critical illness.}, journal = {Acute medicine &amp; surgery}, volume = {12}, number = {1}, pages = {e70068}, pmid = {40469413}, issn = {2052-8817}, abstract = {The gut is a target organ that functions as the "motor" of critical illness. In patients with critical illness, the disrupted gut microbiota following infection and injury could cause diarrhea, pneumonia, and systemic inflammation. For maintaining the gut microbiota, therapeutic approaches are required to modulate host responses and prevent systemic inflammation. Probiotics and synbiotics could maintain the gut microbiota and decrease not only the incidence of diarrhea but also that of ventilator-associated pneumonia. The effects of probiotics/synbiotics differ with the type of bacteria and disease severity. Adverse effects of probiotics have been reported; therefore, the selection of safe and effective probiotics/synbiotics is warranted. Refractory diarrhea with prolonged dysbiosis may require a novel intestinal therapy, such as fecal microbiota transplantation, to alleviate gut dysbiosis.}, }
@article {pmid40468650, year = {2025}, author = {Cha, RR and Sonu, I}, title = {Fecal microbiota transplantation: present and future.}, journal = {Clinical endoscopy}, volume = {58}, number = {3}, pages = {352-359}, doi = {10.5946/ce.2024.270}, pmid = {40468650}, issn = {2234-2400}, support = {//Gyeongsang National University Fund/ ; }, abstract = {Fecal microbiota transplantation (FMT) involves transplanting fecal matter from healthy donors into patients with gut dysbiosis to restore microbial balance. It has been proven to be highly effective in treating recurrent Clostridioides difficile infection (CDI), and United States Food and Drug Administration-approved microbiome-based therapies, such as REBYOTA (fecal microbiota live-jslm) and VOWST (fecal microbiota spores live-brpk), offer promising treatment options. Although FMT is widely used to treat recurrent CDI, its use in gastrointestinal and metabolic diseases remains limited. Future research directions include optimizing donor selection, understanding microbial mechanisms, and exploring the potential of FMT for treating other diseases. Ongoing research not only aims to broaden its indications but also improves its safety and efficacy. Emerging therapies such as VE303 (Vedanta) are being studied to refine treatment approaches and expand the use of microbiota-based therapies. Further studies are needed to standardize guidelines, improve patient outcomes, and better define the role of FMT in the treatment of diseases beyond recurrent CDI.}, }
@article {pmid40466419, year = {2025}, author = {Zhang, K and Dong, Y and Ding, Y and Wang, X and Liu, T and Zhong, W and Cao, H}, title = {Illuminating prospects of probiotic Akkermansia muciniphila in intestinal inflammation and carcinogenesis.}, journal = {Microbiological research}, volume = {299}, number = {}, pages = {128240}, doi = {10.1016/j.micres.2025.128240}, pmid = {40466419}, issn = {1618-0623}, abstract = {Akkermansia muciniphila (A. muciniphila) is portrayed as an advantageous enteric bacterium with a particular property of mucin utilization. Emerging data suggest A. muciniphila can reshape gut chronic inflammation, enhance intestinal epithelial tight junctions, and sensitize toll-like receptors 2 (TLR2) and TLR4 to restrain the infiltrating cytotoxic T lymphocytes and macrophages. As well, analogous role is detected in surface A. muciniphila-coated pili, outer-membrane protein Amuc_1100, β-galactosidase enzyme Amuc_2172, and extracellular vesicles. We rendered insights into empirical evidence on molecular mechanisms mediated by A. muciniphila in inflammatory bowel disease and intestinal cancers which include colitis-associated colorectal cancer and colorectal cancer. We discussed its potential preventive and therapeutic benefits on immune checkpoint inhibitors therapy. A. muciniphila supplementation through diet, probiotics-prebiotics, fecal microbiota transplantation, and certain drugs, would be a promising therapeutic strategy. Nevertheless, data profiles decipher A. muciniphila is linked to multiple sclerosis and Parkinson's disease occurrence and evolvement. Thus, how to avoid the deleterious effects triggered by A. muciniphila warrants further exploration. It ought to be considered to conduct a critical and cautious analysis of the next-generation beneficial microbe manipulation ahead of clinical application.}, }
@article {pmid40069438, year = {2025}, author = {Park, M and Jung, J and Lee, JA and Lee, E and Lee, H and Eom, HS and Park, HJ}, title = {Understanding gut Microbiome changes in Korean children, adolescents, and young adults with hematologic malignancies.}, journal = {Annals of hematology}, volume = {104}, number = {5}, pages = {2947-2961}, pmid = {40069438}, issn = {1432-0584}, support = {2011500-1//National Cancer Center, Korea/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Adolescent ; Child ; Male ; Female ; *Hematologic Neoplasms/therapy/microbiology/epidemiology ; Young Adult ; Republic of Korea/epidemiology ; Hematopoietic Stem Cell Transplantation ; Feces/microbiology ; Adult ; }, abstract = {We investigated whether changes in the gut microbiome composition are associated with infections and immunologic complications during the treatment of Korean children, adolescents, and young adults (AYAs) with hematologic malignancies. We analyzed stool samples from 26 patients and 10 healthy siblings using 16 S rRNA gene sequencing. At diagnosis, patients exhibited a lower abundance of Lachnospiraceae and a higher abundance of Enterococcaceae than their healthy siblings. Both the Chao1 and Shannon diversity indices declined from diagnosis to the end of induction chemotherapy. Patients with fever during induction had a lower baseline microbial diversity and higher Ruminococcus g4 abundance than those without fever. The use of either meropenem or piperacillin/tazobactam during induction was correlated with reduced richness and altered composition of the gut microbiome after induction. The Chao index and beta diversity of stool samples significantly differed before conditioning when compared with those of healthy siblings. During allogeneic hematopoietic stem cell transplantation, both the Chao1 and Shannon diversity indices significantly decreased on day 14 but recovered by day 60. Our study highlights the role of gut microbiome diversity and compositional structure in influencing treatment outcomes in children and AYA with hematologic malignancies, providing the information required to improve the gut microbiome configuration and treatment outcomes.}, }
@article {pmid40464639, year = {2025}, author = {Zhang, Q and Liu, Y and Li, Y and Bai, G and Pang, J and Wu, M and Li, J and Zhao, X and Xia, Y}, title = {Implications of gut microbiota-mediated epigenetic modifications in intestinal diseases.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2508426}, doi = {10.1080/19490976.2025.2508426}, pmid = {40464639}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Epigenesis, Genetic ; Animals ; Dysbiosis/microbiology/therapy ; DNA Methylation ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; *Intestinal Diseases/microbiology/genetics/therapy ; Probiotics ; Inflammatory Bowel Diseases/microbiology/genetics/therapy ; Colorectal Neoplasms/microbiology/genetics ; }, abstract = {Intestinal diseases are highly prevalent, affecting millions worldwide and significantly contributing to global morbidity. The treatment of complex disorders, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), remains challenging due to multifactorial etiologies, diverse patient responses, and the limitations of current therapeutic strategies. Although the gut microbiota clearly plays a role in regulating the onset of intestinal diseases, few studies have explored the epigenetic factors by which the microbiota contributes to disease development. Here, the latest insights into the molecular mechanisms underlying the bidirectional influence between gut microbiota and epigenetic modifications are discussed, including DNA methylation, histone modifications, non-coding RNAs, and N6-methyladenosine (m[6]A). Importantly, mechanistic studies based on animal models or human cells have demonstrated that the gut microbiota, and other environmental factors, influence targeted gene expression and activate immune pathways through host epigenetic dysregulation, which are closely associated with the development of IBD and CRC. Furthermore, potential microbiome interventions, including probiotics, prebiotics and postbiotics, fecal microbiota transplantation (FMT), dietary modifications, and phage therapy, have been proposed as innovative therapeutic strategies to correct these abnormal epigenetic patterns associated with the diseases. Overall, addressing microbiome dysbiosis and its epigenetic consequences presents a promising frontier in the treatment of intestinal diseases, offering the potential to not only restore microbial balance but also provide more targeted and personalized therapeutic strategies for better patient outcomes.}, }
@article {pmid40464558, year = {2025}, author = {Ruan, Y and Zhu, T and Yang, R and Su, F and An, C and Hu, Z and Li, X and Li, Y and Chen, P and Shao, X and Qin, J and Chen, H and Chen, R}, title = {Donor-derived microbial engraftment and gut microbiota shifts associated with weight loss following fecal microbiota transplantation.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0012025}, doi = {10.1128/aem.00120-25}, pmid = {40464558}, issn = {1098-5336}, abstract = {Fecal microbiota transplantation (FMT) is a promising treatment for microbiota dysbiosis and may provide metabolic benefits for obesity. However, its mechanisms and variability in clinical outcomes remain poorly understood. This 12-week multicenter, single-arm study evaluated the efficacy of FMT for weight loss and explored the role of donor-derived microbial engraftment and functional shifts in mediating weight loss among overweight and obese individuals. Twenty-three participants (body mass index ≥24 kg/m[2]) without diabetes received three biweekly FMT sessions via a nasojejunal tube. Fecal samples from participants and donors were analyzed using metagenomic sequencing. By week 12, 52% of participants were classified as responders, achieving significant weight loss of ≥5% from baseline, with an average weight loss of 7.98 ± 2.69 kg (P < 0.001). In contrast, non-responders lost 2.90 ± 1.89 kg (P < 0.001). Responders exhibited a significantly higher proportion of donor-derived microbial strains post-FMT compared to non-responders (37.8% vs 15.2%, P = 0.020). Notably, key taxa, including Phascolarctobacterium (P = 0.034) and Acidaminococcaceae (P = 0.012), increased significantly in abundance in responders post-FMT, indicating successful microbial engraftment as a critical determinant of therapeutic success. These findings suggest that FMT is a viable intervention for weight loss in obese individuals. Successful donor-derived microbial engraftment strongly correlates with weight loss efficacy, highlighting the potential of microbiota-targeted therapies in obesity management and providing insights into the mechanisms underlying FMT outcomes.IMPORTANCEPrior research indicates that fecal microbiota transplantation (FMT) is a promising treatment for diseases related to microbiota imbalance, potentially providing metabolic benefits for obesity. However, the specific role of donor-derived microbial engraftment in driving clinical efficacy has remained unclear. In this study, we evaluated the efficacy of FMT in promoting weight loss and explored the role of donor-derived bacterial strains in this process. Our findings demonstrate that the successful engraftment of specific donor-derived taxa, such as Phascolarctobacterium and Acidaminococcaceae, is strongly associated with significant weight loss. This highlights the critical interplay between donor microbiota and recipient gut environment. These findings underscore the potential of microbiota-targeted therapies as a novel strategy for obesity management.CLINICAL TRIALSThis study is registered with the Chinese Clinical Trial Registry as ChiCTR1900024760.}, }
@article {pmid40463945, year = {2025}, author = {Wu, C and Mi, Y and Song, J and Zhang, M and Wang, C}, title = {The Regulatory Effect of Human Umbilical Cord Mesenchymal Stem Cells on the Gut Microbiota in Diabetic Nephropathy Rats.}, journal = {Iranian journal of biotechnology}, volume = {23}, number = {1}, pages = {}, pmid = {40463945}, issn = {1728-3043}, abstract = {BACKGROUND: Chronic inflammation is increasingly recognized as a key factor in the progression of diabetic kidney disease (DKD). By discovering that the regulation of gut microbiota plays an important role in diabetic kidney disease, human umbilical cord mesenchymal stem cells (HU-MSCs) explore the mechanism of fibrosis in diabetic kidney disease through the regulation of chronic inflammation, providing new clinical insights for the prediction, diagnosis, and treatment of diabetic kidney disease.<br><br>OBJECTIVES: This study explores the regulatory effects of HU-MSCs on gut microbiota and their protective role on the intestinal barrier in diabetic nephropathy rats.<br><br>MATERIAL AND METHOD: Diabetic kidney disease (DKD) was induced in SD rats via intraperitoneal injection of streptozotocin. Three groups were established: control group, diabetic kidney disease (DKD) group, and treatment group (DKD+HU-MSCs) (10 rats each). After diabetic kidney disease (DKD) modeling, rats in the treatment group (DKD+HU-MSCs) received 2&#xd7;10[6] HU-MSCs via tail vein injection weekly for four weeks. Blood, urine, kidney, and colon tissues were collected post-treatment. Pathological changes were observed microscopically; immunohistochemistry detected tight junction proteins ZO-1 and Occludin in colon tissues. DiR-labeled HU-MSCs distribution was assessed with in vivo imaging, and immunohistochemistry evaluated human mesenchymal stem cell markers CD44 and CD90. Fecal samples underwent metagenomic sequencing for gut microbiota analysis.<br><br>RESULTS: HU-MSCs transplantation significantly reduced Blood Urea Nitrogen (BUN), Serum Creatinine (SCr), and 24-hour urinary protein levels (all P < 0.05) and improved renal pathology. Markers CD44 and CD90 were present in DKD rat colon tissues. Tight junction proteins Occludin and ZO-1 were decreased in DKD rats but increased following HU-MSCs treatment. Metagenomic analysis showed enhanced abundance of beneficial bacteria (Bifidobacterium and Lactobacillus) with HU-MSCs. Urinary protein was positively correlated with Prevotella and negatively with Ligilactobacillus (p < 0.05).<br><br>CONCLUSIONS: HU-MSCs may improve intestinal barrier function in diabetic kidney disease (DKD) rats by restoring gut microbiota structure and increasing intestinal tight junction proteins, offering a potential pathway for enhancing renal function.}, }
@article {pmid40462220, year = {2025}, author = {Chen, M and Pan, J and Song, Y and Liu, S and Sun, P and Zheng, X}, title = {Correction: Effect of inulin supplementation in maternal fecal microbiota transplantation on the early growth of chicks.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {138}, pmid = {40462220}, issn = {2049-2618}, }
@article {pmid40272189, year = {2025}, author = {Zhang, L and Wang, H and Zhao, L and Zhang, J and Sun, W and Chu, J and Zhao, H and Yang, C and Yan, S and Chen, X and Xu, D}, title = {Unraveling the interplay between mesenchymal stem cells, gut microbiota, and systemic sclerosis: therapeutic implications.}, journal = {Microbiology spectrum}, volume = {13}, number = {6}, pages = {e0157624}, pmid = {40272189}, issn = {2165-0497}, support = {82171790//National Natural Science Foundation of China/ ; 82201925//National Natural Science Foundation of China/ ; 32000075//National Natural Science Foundation of China/ ; ZR2024QC071//Natural Science Foundation of Shandong Province/ ; ZR2024MH079//Natural Science Foundation of Shandong Province/ ; ZR2022QH203//Natural Science Foundation of Shandong Province/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Scleroderma, Systemic/therapy/chemically induced/microbiology/pathology ; Animals ; *Mesenchymal Stem Cells/physiology/metabolism ; Mice ; Humans ; *Mesenchymal Stem Cell Transplantation ; Disease Models, Animal ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Bleomycin ; Mice, Inbred C57BL ; Feces/microbiology ; Female ; }, abstract = {UNLABELLED: Systemic sclerosis (SSc) is an autoimmune disease with progressive fibrotic disorders in multiple organs. Mesenchymal stem cells (MSCs) have shown great potential in treating SSc, but the exact regulatory mechanism is not fully understood. In this study, we used human umbilical cord-derived MSCs (hUC-MSCs) to treat SSc mice induced by bleomycin. The gut microbiota composition and predicted functions were analyzed using 2bRAD sequencing of fecal samples from control, SSc, and MSCs-treated mice. Treatment with MSCs improved the bleomycin-induced SSc mice, characterized by significantly reduced collagen deposition and dermal thickness. The gut microbiota of SSc mice exhibited lower species evenness and was clearly separated from the control mice based on beta diversity. MSC treatment led to a significant reduction of conditionally pathogenic bacteria enriched in SSc, including Akkermansia muciniphila and Parasutterella excrementihominis. Conversely, the relative abundance of butyrate-producing bacteria, such as Roseburia, Butyricicoccus porcorum, and Gemmiger formicilis, was notably increased in MSCs-treated SSc mice. Additionally, the functional analysis revealed that MSCs intervention effectively enhanced sulfur metabolism, tryptophan metabolism, citrate cycle, RNA polymerase, and beta-lactam resistance. In summary, the findings in the present study have suggested the close association between gut microbiota and metabolic dysbiosis in mice with SSc. The administration of MSCs has been shown to regulate the disrupted metabolic pathways in SSc mice, thus restoring the normal function of the gut microbiota. This study provides valuable insights into the specific gut microbiota and metabolic pathways involved in the efficacy of MSC treatment, thereby proposing a novel therapeutic strategy for SSc.<br><br>IMPORTANCE: Human umbilical cord-derived mesenchymal stem cells (HUC&#x2011;MSCs) demonstrate efficacy in alleviating skin thickening and collagen deposition in systemic sclerosis (SSc) mice, which also regulate the gut microbiota composition and function. Specifically, MSC intervention leads to a notable increase in butyrate-producing bacteria, a decrease in Akkermansia muciniphila and Parasutterella excrementihominis, and a reversal of the dysregulated microbial function in SSc mice. These findings underscore the potential significance of gut microbiota in the therapeutic effects of MSCs in SSc.}, }
@article {pmid40462165, year = {2025}, author = {Gao, H and Bai, H and Su, Y and Gao, Y and Fang, H and Li, D and Yu, Y and Lu, X and Xia, D and Mao, D and Luo, Y}, title = {Fecal microbiota transplantation from Helicobacter pylori carriers following bismuth quadruple therapy exacerbates alcohol-related liver disease in mice via LPS-induced activation of hepatic TLR4/NF-κB/NLRP3 signaling.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {627}, pmid = {40462165}, issn = {1479-5876}, support = {42377426//National Natural Science Foundation of China/ ; 42077382//National Natural Science Foundation of China/ ; 21JCYBJC01200//Tianjin Municipal Natural Science Foundation/ ; 2023220//Research Project on Integrated Traditional Chinese and Western Medicine of Tianjin Municipal Health Commission/ ; }, abstract = {BACKGROUND: Helicobacter pylori infection is common in patients with alcohol-related liver disease (ALD), and bismuth quadruple therapy (BQT) is widely used for eradication. However, its impact on ALD remains unclear. This study aims to characterize BQT-induced gut microbiota alterations in asymptomatic H. pylori carriers and evaluate their effect on an ALD mouse model.<br><br>METHODS: Metagenomic sequencing was conducted to assess the gut microbiota composition of individuals before and after BQT. Fecal microbiota transplantation (FMT) from these donors was performed in an ALD mouse model. Gut microbiota in mice was analyzed by 16S rRNA sequencing. Liver and intestinal parameters were assessed using western blot, RT-qPCR, histopathology, ELISA, and flow cytometry.<br><br>RESULTS: BQT treatment significantly altered the gut microbiota in H. pylori carriers, increasing the abundance of opportunistic pathogens, including Klebsiella pneumoniae, Escherichia coli, Klebsiella quasipneumoniae, and Klebsiella variicola, while decreasing beneficial bacteria such as Bifidobacterium, Eubacterium, Bacteroides, Faecalibacterium, and Blautia. In ALD mice receiving FMT from post-BQT donors, exacerbated gut dysbiosis was observed, marked by an enrichment of Enterobacteriaceae and Escherichia-Shigella. These microbiota changes were associated with impairment of intestinal barrier integrity, as evidenced by reduced levels of mucins, tight junction proteins, and antimicrobial peptides, along with a decrease in Treg cells and an increase in Th17 and Th1 cells. Additionally, this dysbiosis led to elevated serum lipopolysaccharide (LPS) levels, which activated the hepatic NLRP3 inflammasome pathway and subsequently increased IL-18 and IL-1&#x3b2; levels. Furthermore, liver function and oxidative stress markers, including ALT, AST, MDA, GSSG/GSH ratio, and SOD, were significantly elevated, indicating severe liver dysfunction and increased oxidative stress. Finally, probiotic supplementation effectively mitigated the negative effects of BQT-induced gut microbiota remodeling on ALD in mice.<br><br>CONCLUSIONS: BQT markedly alters the gut microbiota in H. pylori carriers, promoting dysbiosis that exacerbates ALD in mice via LPS-mediated activation of hepatic inflammatory pathways. These findings highlight the need for careful consideration of BQT use in ALD patients.}, }
@article {pmid40461622, year = {2025}, author = {Ferreira, J}, title = {Fecal microbiota transplantation therapy.}, journal = {Lab animal}, volume = {54}, number = {6}, pages = {133}, doi = {10.1038/s41684-025-01564-x}, pmid = {40461622}, issn = {1548-4475}, }
@article {pmid40461059, year = {2025}, author = {Laiola, M and Koppe, L and Larabi, A and Thirion, F and Lange, C and Quinquis, B and David, A and Le Chatelier, E and Benoit, B and Sequino, G and Chanon, S and Vieille-Marchiset, A and Herpe, YE and Alvarez, JC and Glorieux, G and Krukowski, H and Geert, HRB and Raes, J and Fouque, D and Massy, ZA and Ehrlich, SD and Stengel, B and Wagner, S and , }, title = {Toxic microbiome and progression of chronic kidney disease: insights from a longitudinal CKD-Microbiome Study.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-334634}, pmid = {40461059}, issn = {1468-3288}, abstract = {BACKGROUND: The gut microbiota has been linked to non-communicable diseases, including chronic kidney disease (CKD). However, the relationships between gut microbiome composition changes, uraemic toxins (UTs) accumulation, and diet on CKD severity and progression remain underexplored.<br><br>OBJECTIVE: To characterise relationships between gut microbiome composition and functionality, UTs diet, and CKD severity and progression, as well as assess microbial contributions to UTs accumulation through mice faecal microbiota transplantation (FMT).<br><br>DESIGN: This study profiled the gut microbiome of 240 non-dialysis patients with CKD (CKD-REIN cohort) using shotgun metagenomics, with follow-up in 103 patients after 3 years, with comparisons with healthy volunteers from the Milieu Int&#xe9;rieur cohort. A multiomics approach identifies features associated with CKD severity (and progression), with validation in an independent Belgian cohort. Experimental models used FMT to test CKD gut microbiome effects on UTs and kidney fibrosis. Changes in gut microbiome over time were evaluated, and the impact of diet on these changes was assessed.<br><br>RESULTS: Compared with matched healthy controls, patients with CKD exhibited gut microbiota alteration, with enrichment of UT precursor-producing species. Patients with severe CKD exhibited higher UT levels and greater enrichment of UT (precursor)-producing species in the microbiota than patients with moderate CKD. Over time, UT (precursor)-producing species increased, and a plant-based low protein diet appeared to mitigate these changes. FMT from patients with CKD to antibiotic-treated CKD model mice increased serum UT levels and exacerbated kidney fibrosis.<br><br>CONCLUSIONS: This study highlights the role of the microbiome and UTs in CKD, suggesting a potential therapeutic target to slow disease progression.}, }
@article {pmid40460824, year = {2025}, author = {Gogokhia, L and Tran, N and Grier, A and Nagayama, M and Xiang, G and Funez-dePagnier, G and Lavergne, A and Ericsson, C and Ben Maamar, S and Zhang, M and Battat, R and Scherl, E and Lukin, DJ and Longman, RS}, title = {Donor composition and fiber promote strain engraftment in a randomized controlled trial of fecal microbiota transplant for ulcerative colitis.}, journal = {Med (New York, N.Y.)}, volume = {}, number = {}, pages = {100707}, doi = {10.1016/j.medj.2025.100707}, pmid = {40460824}, issn = {2666-6340}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging treatment for ulcerative colitis (UC), but the impact of prebiotic fiber on FMT efficacy for UC is unclear. We performed a randomized, double-blind, placebo-controlled clinical trial to examine the efficacy of FMT with and without dietary fiber supplementation in patients with UC.<br><br>METHODS: 27 patients with mild to moderate UC were randomized to receive a single FMT or placebo with or without psyllium fiber supplementation for 8 weeks. The primary outcome was clinical response at week 8, and secondary outcomes included endoscopic improvement and clinical remission. Metagenomic sequencing of fecal DNA was analyzed to determine taxonomic profiles and donor strain engraftment.<br><br>FINDINGS: The trial was terminated early due to manufacturer discontinuation of FMT product. FMT induced clinical response, remission, and endoscopic improvement in UC patients compared to placebo (p < 0.05), but fiber did not improve clinical outcomes of FMT. Recipient microbiome composition post-FMT shifted toward donor composition in responders and non-responders, but the durability of this change was stronger in responders. Clinical response and durable change in microbiome composition following FMT was donor dependent. Strain tracking analysis also demonstrated a donor-dependent variability in the rate of successful engraftment and identified a consortium of engrafted bacteria associated with treatment response or fiber supplementation.<br><br>CONCLUSIONS: Single-dose FMT demonstrated clinical efficacy for mild to moderate UC compared to placebo but revealed no benefit of fiber supplementation. These results highlight proof of concept that donor selection and prebiotic fiber can shape strain-level engraftment. This study was registered at ClinicalTrials.gov: NCT03998488.<br><br>FUNDING: National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK128257, to R.S.L.).}, }
@article {pmid40458824, year = {2025}, author = {Huang, Y and Huang, J and Li, Y and Xu, T and Quan, G and Xu, P and Yang, X and Liu, Z and Xie, W}, title = {Therapeutic efficacy of fecal microbiota transplantation in severe food intolerance: a case report.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1594022}, pmid = {40458824}, issn = {2296-861X}, abstract = {This report presents the first documented application of fecal microbiota transplantation (FMT) for the management of extensive multi-food intolerance involving 52 specific foods in a pediatric patient with autism spectrum disorder (ASD). A 7 years-old autistic child was diagnosed with food intolerance to 52 items, presenting with generalized rashes, diarrhea, and malnutrition (BMI of 12.9) upon exposure or ingestion of the implicated foods. The child received oral fecal microbiota capsule treatment, with a daily dose of nine capsules (a total of 120 capsules per course) for two consecutive treatment courses. The rashes resolved, the child regained tolerance to previously intolerable foods, nutritional status improved, and stool consistency normalized. This case suggests that FMT may hold therapeutic potential for managing food intolerance in autistic patients.}, }
@article {pmid40457025, year = {2025}, author = {Elkrief, A and Pidgeon, R and Maleki Vareki, S and Messaoudene, M and Castagner, B and Routy, B}, title = {The gut microbiome as a target in cancer immunotherapy: opportunities and challenges for drug development.}, journal = {Nature reviews. Drug discovery}, volume = {}, number = {}, pages = {}, pmid = {40457025}, issn = {1474-1784}, abstract = {The gut microbiome has a critical role in shaping the patient's immune response and influencing the efficacy of anticancer immunotherapy. Emerging evidence suggests that modulating the gut microbiome through interventions such as faecal microbiota transplantation, probiotics, prebiotics and lifestyle modifications may enhance therapeutic outcomes. Consequently, drug development efforts in immuno-oncology have expanded to explore microbiome-based therapeutic strategies. In this Review, we examine the rationale for targeting the microbiome in cancer treatment, highlighting key advances in clinical microbiome characterization and their implications for immunotherapy. We discuss findings from recent clinical trials evaluating microbiome-based interventions and address the challenges associated with translating these approaches into clinical practice. Finally, we outline future directions for the development and integration of microbiome-targeted therapies in oncology, with a focus on optimizing efficacy, safety and patient stratification strategies.}, }
@article {pmid40456559, year = {2025}, author = {Hu, Y and Wang, Y and Gao, H and Yang, G and Xie, J and He, Z and Lv, S and Gu, F and Huang, C and Hu, W}, title = {Piperine Improves DSS-Induced Colitis in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.8491}, pmid = {40456559}, issn = {1099-1573}, support = {ZDYF2024XDNY177//Hainan Province Science and Technology Special Fund/ ; 2023YFD1600200//National Key Research and Development Program of China/ ; 1630012025119//China Central Public-Interest Scientific Institution Basal Research Fund/ ; }, abstract = {Inflammatory bowel disease (IBD) is a global health concern with limited therapeutic options. Previous studies have demonstrated that piperine exhibited anti-inflammatory effects both in vitro and in vivo. However, its potential to ameliorate colitis in mice through modulation of gut microbiota has not been explored. This study aimed to investigate the role of gut microbiota in the protective effects of piperine against colitis using a dextran sulfate sodium (DSS)-induced mouse model. Mice were administered piperine (12.5 and 25 mg/kg) prior to DSS exposure. Fecal microbiota transplantation (FMT) was then performed, after which we evaluated colitis symptoms, inflammation levels, and intestinal barrier function. Subsequently, 16S rDNA-based high-throughput sequencing was employed to analyze the microbial composition of the mouse cecal contents. Piperine administration increased the colon length, decreased the spleen index, and improved colon histopathology. Furthermore, piperine modulated inflammatory responses by inhibiting NF-κB signaling, thereby reducing the release of pro-inflammatory cytokines and mediators. It also enhanced intestinal barrier integrity by increasing the expression of claudin-1, claudin-3, ZO-1, occludin, and mucin 2. Notably, the 16S rDNA sequencing results revealed that piperine increased the abundance of Dubosiella in the gut. Piperine effectively protected mice from DSS-induced colitis, suppressed inflammation, and improved poor intestinal barrier function. It reshaped the intestinal microbiota, ultimately alleviating DSS-induced colitis in mice. Our research highlighted the significant role of gut microbiota in the piperine-mediated alleviation of intestinal damage and suggested its therapeutic potential for promoting gut health and reducing the risk of colitis.}, }
@article {pmid40455241, year = {2025}, author = {Yi, LT and Wang, XY and Zhou, L and Cheng, J and Xu, GH and Zhu, JX}, title = {Polysaccharides from Black Mulberry Attenuate Colitis through Gut Microbiota Mediated TNF-α/pNF-κB/ICAM-1 Signaling Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c01870}, pmid = {40455241}, issn = {1520-5118}, abstract = {Colitis is characterized by immune dysregulation and gut microbiota imbalance. This study investigates the therapeutic effects of polysaccharides from black mulberry (PBM) on dextran sulfate sodium-induced colitis in mice. PBM administration significantly alleviated colitis symptoms, including body weight loss, histological damage, and inflammation, while enhancing antioxidant capacity and strengthening tight junction protein expression. PBM modulated gut microbiota composition, notably increasing Weissella spp., which correlated with elevated short-chain fatty acids (SCFAs) and decreased pro-inflammatory markers. Colonic RNA sequencing revealed the role of PBM in attenuating colitis via the TNF-α/NF-κB/ICAM-1 signaling pathway. Fecal microbiota transplantation (FMT) from PBM-treated mice confirmed that microbiota modulation from PBM contributed to these therapeutic effects. These findings suggest PBM as a natural therapeutic agent for colitis, offering a multifaceted approach to restoring gut homeostasis through microbiota modulation and inflammatory pathway regulation. This study provides new insights into dietary polysaccharides as potential adjunctive therapies for colitis.}, }
@article {pmid40454811, year = {2025}, author = {Millard, SA and Vendrov, KC and Young, VB and Seekatz, AM}, title = {Host origin of microbiota drives functional recovery and Clostridioides difficile clearance in mice.}, journal = {mBio}, volume = {}, number = {}, pages = {e0110825}, doi = {10.1128/mbio.01108-25}, pmid = {40454811}, issn = {2150-7511}, abstract = {UNLABELLED: Colonization resistance provided by the gut microbiota is essential for resisting both initial Clostridioides difficile infection (CDI) and potential recurrent infection (rCDI). Although fecal microbiota transplantation (FMT) has been successful in treating rCDI by restoring microbial composition and function, mechanisms underlying the efficacy of standardized stool-derived products remain poorly understood. Using a combination of 16S rRNA gene-based and metagenomic sequencing alongside metabolomics, we investigated microbiome recovery following FMT from human and murine donor sources in a mouse model of rCDI. We found that a human-derived microbiota was less effective in clearing C. difficile compared to a mouse-derived microbiota, despite recovery of taxonomic diversity, compositional changes, and bacterial functions typically associated with clearance. Metabolomic analysis revealed deficits in secondary metabolites compared to those that received murine FMT, suggesting a functional remodeling between human microbes in their new host environment. Collectively, our data revealed additional environmental, ecological, or host factors to consider in FMT-based recovery from rCDI.<br><br>IMPORTANCE: Clostridioides difficile is a significant healthcare-associated pathogen, with recurrent infections presenting a major treatment challenge due to further disruption of the microbiota after antibiotic administration. Despite the success of fecal microbiota transplantation (FMT) for the treatment of recurrent infection, the mechanisms mediating its efficacy remain underexplored. This study reveals that the effectiveness of FMT may be compromised by a mismatch between donor microbes and the recipient environment, leading to deficits in key microbial metabolites. These findings highlight additional factors to consider when assessing the efficacy of microbial-based therapeutics for C. difficile infection (CDI) and other conditions.}, }
@article {pmid40454495, year = {2025}, author = {Bjørklund, G and Butnariu, M and Dadar, M and Semenova, Y}, title = {The Gut Microbiota-anxiety Connection: Evidence, Mechanisms, and Therapeutic Strategies.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673356125250409182218}, pmid = {40454495}, issn = {1875-533X}, abstract = {The gut-brain axis (GBA), a bidirectional communication system between the gut and the brain, has emerged as a critical player in mental health. The interest in the connection between anxiety disorders (AD) and the gut microbiota is growing. This paper provides an overview of gut microbiota's role in dysregulation in anxiety, including alterations in gut microbiota (dysbiosis), leaky gut, metabolic endotoxemia, and the effect of antipsychotic medications. The mechanisms underlying the gut microbiota-anxiety (GMA) connection, such as neurotransmitter production, immune dysregulation, and GBA communication, are discussed. Furthermore, the paper explores gut microbiota- based therapeutic strategies, including probiotics, prebiotics, symbiotics, fecal microbiota transplantation, and dietary interventions, as potential approaches for anxiety management. This research field's clinical implications and future directions are also examined, underscoring that more studies are needed on gut microbiota's role in anxiety disorders. The conclusion highlights the importance of this ongoing research and the potential for personalized therapeutic interventions, instilling hope and optimism for the future of anxiety management and providing reassurance about the potential for personalized therapeutic interventions in this field.}, }
@article {pmid40454186, year = {2025}, author = {Sharma, VK}, title = {Diabetes-induced depression: unravelling the role of gut dysbiosis.}, journal = {Journal of diabetes and metabolic disorders}, volume = {24}, number = {1}, pages = {129}, pmid = {40454186}, issn = {2251-6581}, abstract = {Depression is a prevalent yet often underdiagnosed neuropsychiatric comorbidity of type 2 diabetes mellitus (T2DM), significantly complicating disease management, treatment adherence, and overall well-being. Emerging evidence suggests that gut microbiota dysbiosis plays a pivotal role in linking T2DM and depression through mechanisms such as epithelial barrier dysfunction, systemic inflammation, neurotransmitter imbalances, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and impaired neurogenesis. This review aims to explore the mechanistic pathways through which diabetes-induced dysbiosis contributes to depression and to appraise the therapeutic potential of microbiota-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, in mitigating depressive symptoms and improving metabolic outcomes. Understanding this gut-brain interplay may provide novel insights into therapeutic strategies for managing the dual burden of diabetes and depression.}, }
@article {pmid40448308, year = {2025}, author = {Gu, BH and Jung, HY and Rim, CY and Kim, TY and Lee, SJ and Choi, DY and Park, HK and Kim, M}, title = {Comparative Colonisation Ability of Human Faecal Microbiome Transplantation Strategies in Murine Models.}, journal = {Microbial biotechnology}, volume = {18}, number = {6}, pages = {e70173}, pmid = {40448308}, issn = {1751-7915}, support = {2024-ER2113-00//the Korea National Institute of Health (KNIH) research project/ ; 20019505//the Ministry of Trade, Industry &amp; Energy (MOTIE, Korea)/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Humans ; Mice ; *Gastrointestinal Microbiome ; *Feces/microbiology ; Disease Models, Animal ; *Bacteria/classification/growth &amp; development/isolation &amp; purification/genetics ; Dysbiosis/therapy/microbiology ; Male ; Models, Animal ; }, abstract = {The gut microbiome plays a crucial role in maintaining intestinal homeostasis and influencing immune-mediated diseases. Human faecal microbiota transplantation (FMT) is often employed in murine models to investigate the role of human microbes in disease regulation, but methods for effective colonisation require refinement. This study aimed to assess the colonisation efficiency of human microbiota in a murine model using FMT with human faeces, focusing particularly on the impact of gut microbiota depletion via polyethylene glycol (PEG) and comparing oral-gastric gavage with enema administration routes. Our findings revealed that PEG-induced depletion enhanced human microbiome colonisation in mice. Oral-gastric gavage prolonged colonisation, while enema administration facilitated quicker resolution of dysbiosis, both inducing selective human microbial colonisation in a time-dependent manner. Notably, genera such as Bacteroides, Blautia, Medicaternibacter and Bifidobacteria were successfully colonised, whereas Roseburia, Anaerostipes, Anaerobutyricum and Faecalibacterium failed to establish in the murine gut post-FMT. These findings highlight the challenges of replicating human gut microbiota in murine models and underscore the importance of selecting appropriate FMT methods based on desired outcomes. This study provides valuable insights into the colonisation dynamics of human microbiota in mice, contributing to the development of more effective FMT strategies for disease treatment.}, }
@article {pmid40448218, year = {2025}, author = {Gao, ZK and Fan, CY and Zhang, BW and Geng, JX and Han, X and Xu, DQ and Arshad, M and Sun, HX and Li, JY and Jin, X and Mu, XQ}, title = {Cardiac function of colorectal cancer mice is remotely controlled by gut microbiota: regulating serum metabolites and myocardial cytokines.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {53}, pmid = {40448218}, issn = {2524-4671}, support = {NSFC81903631//The National Natural Science Foundation of China/ ; }, abstract = {Several studies have indicated that the dysregulation of microbial metabolites and the inflammatory environment resulting from microbial dysbiosis may contribute to the occurrence and progression of cardiovascular diseases. Therefore, restoring the disordered gut microbiota in patients with colorectal cancer by fecal microbiota transplantation (FMT) has the potential to reduce the incidence of cardiac disease. In this study, we identified cardiac dysfunction in azomethane and dextran sodium sulfate-induced colorectal cancer mice. Intestinal microbes from healthy mice were transferred to colorectal cancer mice, which vastly reversed the disorder of the gut microbiota and effectively alleviated cardiac dysfunction. Moreover, FMT regulated the expression of serum metabolites such as uridine triphosphate (UTP), tiamulin, andrographolide, and N-Acetyl-D-glucosamine, as well as cytokines like TGF-β, IRF5, and β-MHC in the heart. These findings uncover that the disturbed gut microbiota causes cardiac dysfunction in colorectal cancer mice by modulating the expression of serum metabolites and cytokines, which could be alleviated by treatment with FMT.}, }
@article {pmid39752608, year = {2025}, author = {Holtan, SG and Bolaños-Meade, J and Al Malki, MM and Wu, J and Kitko, CL and Reshef, R and Rezvani, AR and Shaffer, BC and Solh, MM and Yao, JM and Runaas, L and Elmariah, H and Larkin, KT and El Jurdi, N and Gooptu, M and Loren, AW and Hall, AC and Alousi, AM and Jamy, O and Clark, W and Kean, L and Bhatt, AS and Perales, MA and Applegate, K and Efebera, YA and Leifer, E and Jones, RJ and Horowitz, MM and Mattila, D and Saber, W and Hamadani, M and Martens, MJ}, title = {Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {43}, number = {8}, pages = {912-918}, pmid = {39752608}, issn = {1527-7755}, support = {U10 HL069294/HL/NHLBI NIH HHS/United States ; U24 CA076518/CA/NCI NIH HHS/United States ; U24 HL138660/HL/NHLBI NIH HHS/United States ; UG1 HL138645/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Cyclophosphamide/therapeutic use/administration &amp; dosage/adverse effects ; *Patient Reported Outcome Measures ; *Graft vs Host Disease/prevention &amp; control ; *Quality of Life ; *Bone Marrow Transplantation/adverse effects ; Female ; Male ; Middle Aged ; Adult ; *Immunosuppressive Agents/therapeutic use ; Methotrexate/administration &amp; dosage/therapeutic use ; Tacrolimus/administration &amp; dosage/therapeutic use ; Mycophenolic Acid/administration &amp; dosage/therapeutic use/analogs &amp; derivatives ; Aged ; Treatment Outcome ; }, abstract = {The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant. PRO scores were compared between the arms using inverse probability weighted-independent estimating equation models. The PTCy arm had significantly lower scores on the Lee Chronic GVHD Symptom Scale (P = .01), indicating lower GVHD symptom burden. Lee Scale nutrition and mouth subscores were also better in the PTCy arm compared with the Tac/MTX arm (P < .01 for both). Older participants (age >65 years) reported better Lee Scale psychological subscores than younger participants (P = .003). No significant differences were identified in hemorrhagic cystitis or in the PROMIS subscales between treatment arms. The updated clinical end points at 2 years for the parent trial confirmed that PTCy/Tac/MMF maintained a significant advantage over Tac/MTX in GRFS (42.4% v 28.8%, P = .001). In addition to improved GRFS, patients randomly assigned to the PTCy arm reported lower symptom burden during the first year after transplant.}, }
@article {pmid40447159, year = {2025}, author = {Jeong, SH and Vasavada, SP and Lashner, B and Werneburg, GT}, title = {Fecal microbiota transplant is associated with resolution of recurrent urinary tract infection.}, journal = {Urology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urology.2025.05.052}, pmid = {40447159}, issn = {1527-9995}, abstract = {OBJECTIVE: To investigate the association of fecal microbiota transplant (FMT) therapy, an effective treatment for recurrent C. difficile colitis, with resolution of recurrent UTI (rUTI).<br><br>METHODS: A prospectively accrued database of patients who underwent FMT for recurrent Clostridoides difficile colitis was retrospectively reviewed for individuals with rUTI in the two years prior to FMT. Recurrent UTI status (defined as two UTI episodes in six months or three UTI episodes in one year) and UTI frequency in the two years prior to the FMT were compared to those in the two year follow up period after FMT using the two-tailed Wilcoxin matched pairs signed rank test. A p-value <0.05 was considered statistically significant.<br><br>RESULTS: Of 11 patients who had rUTI in the two years preceding FMT, no patient had rUTI over the follow up period following FMT (p=0.001). The average number of UTIs in the two years prior to FMT was 3.7 (range 2-6), and the average number of UTIs in the follow up period was 0.27 (range 0-1) (p=0.001). The Kaplan-Meier estimate, the median time to UTI recurrence, was 19.6 months (95% CI: 15.2 - 23.9). There was no marked difference in antibiotic susceptibility profiles before and after FMT.<br><br>CONCLUSIONS: FMT was associated with resolution of rUTI and reduction in UTI frequency in this cohort. The results of this study support the hypothesis that modulation of the gut microbiome may reduce rUTI risk, and support a clinical trial to further assess the safety and efficacy of FMT for rUTI.}, }
@article {pmid40446472, year = {2025}, author = {Chen, L and Ahmad, M and Li, J and Li, J and Yang, Z and Hu, C}, title = {Gut microbiota manipulation to mitigate the toxicities of environmental pollutants.}, journal = {Aquatic toxicology (Amsterdam, Netherlands)}, volume = {285}, number = {}, pages = {107425}, doi = {10.1016/j.aquatox.2025.107425}, pmid = {40446472}, issn = {1879-1514}, abstract = {The gut microbiome, commonly termed as a "super organ", plays a crucial role in the modulation of various biological functions associated with metabolism, endocrinology, immunology, and neurology. However, gut microbiome is extremely susceptible to the risks of environmental pollutants, which will drive gut microbial community to dysbiosis. Simultaneously, restoring healthy gut microbiome can protect the hosts from the health hazards of pollutants. It is increasingly verified that probiotics, prebiotics, and fecal microbiota transplantation (FMT) are efficacious measures to manipulate and remediate gut microecosystem. Among various probiotic strains, lactic acid bacteria are the most extensively applied in toxicity mitigation, which is characterized by shaping gut microbiota structure and metabolism, increasing gut epithelial barrier integrity, promoting fecal elimination of pollutants, suppressing inflammation symptoms, and then improving host systemic physiology. Prebiotics are dietary fibers that cannot be digested by the host, but can be fermented by specific gut bacteria to produce short chain fatty acids, which are identified as the key effect molecules in the manifestation of prebiotic toxicity mitigation actions. In addition, by transplanting the entire community of healthy gut microbiota, FMT also shows effective performances in counteracting the adverse effects of environmental pollutants and recovering host animal health. Intriguingly, FMT from young donors is even found to inhibit the toxic disturbances in healthy aging progression. Based on current evidence, this review summarized the findings about using probiotics, prebiotics, and FMT to manipulate gut microbiota and alleviate the health impairment of environmental pollutants. Key mechanistic insights into the interactive behaviors were underlined. Furthermore, the challenges and future directions in harnessing gut microbiota manipulation as a novel therapeutic approach to mitigate pollutant-induced toxicities were postulated. This review is expected to advocate comprehensive scientific research and literally favor the application of health intervention strategies.}, }
@article {pmid40446358, year = {2025}, author = {Porcari, S and Ng, SC and Zitvogel, L and Sokol, H and Weersma, RK and Elinav, E and Gasbarrini, A and Cammarota, G and Tilg, H and Ianiro, G}, title = {The microbiome for clinicians.}, journal = {Cell}, volume = {188}, number = {11}, pages = {2836-2844}, doi = {10.1016/j.cell.2025.04.016}, pmid = {40446358}, issn = {1097-4172}, mesh = {Humans ; *Microbiota ; Clinical Trials as Topic ; }, abstract = {Despite promising evidence in diagnostics and therapeutics, microbiome research is not yet implemented into clinical medicine. Several initiatives, including the standardization of microbiome research, the refinement of microbiome clinical trial design, and the development of communication between microbiome researchers and clinicians, are crucial to move microbiome science toward clinical practice.}, }
@article {pmid40444969, year = {2025}, author = {Xie, J and Kim, T and Liu, Z and Panier, H and Bokoliya, S and Xu, M and Zhou, Y}, title = {Young gut microbiota transplantation improves the metabolic health of old mice.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0160124}, doi = {10.1128/msystems.01601-24}, pmid = {40444969}, issn = {2379-5077}, abstract = {UNLABELLED: The gut microbiota evolves over a lifetime and significantly impacts the aging process. Targeting the gut microbiota represents a novel avenue to delay aging and aging-related physical and mental decline. However, the underlying mechanism by which the microbiota modulates the aging process, particularly age-related physical and behavioral changes is not completely understood. We conducted fecal microbiota transplantation (FMT) from young or old male donor mice to the old male recipients. Old recipients with young microbiota had a higher alpha diversity than the old recipients with old microbiota. Compared to FMT with old microbiota, FMT with young microbiota reduced body weight and prevented fat accumulation in the old recipients. FMT with young microbiota also lowered frailty, increased grip strength, and alleviated depression and anxiety-like behavior in the old recipients. Consistent with observed physical changes, untargeted metabolomic analysis of serum and stools revealed that FMT with young microbiota lowered age-related long-chain fatty acid levels and increased amino acid levels in the old recipients. Bulk RNAseq analysis of the amygdala of the brain showed that FMT with young microbiota downregulated inflammatory pathways and upregulated oxidative phosphorylation in the old recipients. Our results demonstrate that FMT with young microbiota has substantial positive influences on age-related body composition, frailty, and psychological behaviors. These effects are associated with changes in host lipid and amino acid metabolism in the periphery and transcriptional regulation of neuroinflammation and energy utilization in the brain.<br><br>IMPORTANCE: The gut microbiome is a key hallmark of aging. Fecal microbiota transplantation (FMT) using young microbiota represents a novel rejuvenation strategy to delay aging. Our study provides compelling evidence that transplanting microbiota from young mice significantly improved grip strength, frailty, and body composition in aged recipient mice. At the molecular level, FMT improved aging-related metabolic markers in the gut and circulation. Additionally, FMT from young microbiota rejuvenated the amygdala of the aged brain by downregulating inflammatory pathways. This study highlights the importance of metabolic reprogramming via young microbiota FMT in improving physical and metabolic health in elderly recipients.}, }
@article {pmid40443229, year = {2025}, author = {Lee, MA and Slead, T and Suchodolski, J and Tolbert, MK and Marsilio, S}, title = {Adverse events after fecal microbiota transplantation in nine cats: a case series.}, journal = {Journal of feline medicine and surgery}, volume = {27}, number = {5}, pages = {1098612X251337274}, doi = {10.1177/1098612X251337274}, pmid = {40443229}, issn = {1532-2750}, mesh = {Animals ; Cats ; *Cat Diseases/therapy ; *Fecal Microbiota Transplantation/veterinary/adverse effects ; Female ; Male ; Diarrhea/veterinary/therapy ; }, abstract = {This case series describes nine cases of fecal microbiota transplantation in cats and associated adverse events (AEs) from two tertiary referral hospitals. AEs were graded according to criteria established by the Veterinary Cooperative Oncology Group's Common Terminology Criteria for Adverse Events (VCOG-CTCAE v2) for clinical trials. Cats received 5-6 g/kg donor feces 2-6 times for chronic enteropathy (n = 4) or therapy-resistant diarrhea (n = 5). AEs included lethargy (n = 7), vomiting (n = 5), diarrhea (n = 5), weight loss (n = 5), inappetence (n = 5), dehydration (n = 5), abdominal pain (n = 2), gastroenterocolitis based on ultrasound (n = 2) and anorexia (n = 1). Temperatures of up to 103.4°F were noted but did not meet the criteria for AEs (>103.5°F). Cats responded to antimicrobials (metronidazole, marbofloxacin), anthelmintics (fenbendazole), supportive care with fluids, ondansetron and mirtazapine (n = 5), gabapentin (n = 2), pradofloxacin (n = 1) or self-resolved (n = 1). Positive response to fecal microbiota transplantation for the presenting complaint was seen in eight cats (seven complete, one partial and transient).Relevance and novel informationFecal microbiota transplantation is increasing in usage among companion animals. Fecal microbiota transplantations in cats have been rarely described in the literature as have AEs after administration. This case series represents the first description of AEs after fecal microbiota transplantation in cats.}, }
@article {pmid40443227, year = {2025}, author = {Green, GBH and Cox-Holmes, AN and Marlow, GH and Potier, ACE and Wang, Y and Zhou, L and Chen, D and Morrow, CD and McFarland, BC}, title = {Human microbiota influence the immune cell composition and gene expression in the tumor environment of a murine model of glioma.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2508432}, doi = {10.1080/19490976.2025.2508432}, pmid = {40443227}, issn = {1949-0984}, mesh = {Animals ; *Glioma/immunology/microbiology/genetics ; Mice ; Humans ; *Gastrointestinal Microbiome/immunology ; Disease Models, Animal ; *Tumor Microenvironment/immunology/genetics ; *Brain Neoplasms/immunology/microbiology/genetics ; Cell Line, Tumor ; Feces/microbiology ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology ; RNA, Ribosomal, 16S/genetics ; Bacteria/classification/genetics/isolation &amp; purification ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Immunotherapy has shown success against other cancers but not glioblastoma. Previous data has revealed that microbiota influences anti-PD-1 efficacy. We have previously found that, when using gnotobiotic mice transplanted with human fecal microbiota, the gut microbial composition influenced the response to anti-PD-1 in a mouse model of glioma. However, the role of the human microbiota in influencing the mouse immune cells in the glioma microenvironment and anti-PD-1 response was largely unknown. Using two distinct humanized microbiome (HuM) lines, we used single-cell RNA sequencing (scRNA-seq) to determine how gut microbiota affect immune infiltration and gene expression in a murine glioma model.<br><br>METHODS: 16S rRNA sequencing was performed on fecal samples from HuM1 (H1) and HuM2 (H2) mice. Mice were intracranially injected with murine glioma cells (GL261), and on day 13 treated with one dose of isotype control or anti-PD1. Mice were euthanized on day 14 for analysis of all immune cells in the tumors by scRNA-seq.<br><br>RESULTS: HuM1 and HuM2 mice had different microbial populations, with HuM1 being primarily dominated via Alistipes, and HuM2 being primarily composed of Odoribacter. Sc-RNA-seq of the tumor immune cells revealed 21 clusters with significant differences between H1 and H2 samples with a larger population of M1 type macrophages in H1 samples. Gene expression analysis revealed higher expression of inflammatory markers in the M1 population in H2 mice treated with anti-PD-1.<br><br>CONCLUSIONS: Microbial gut communities influence the presence and gene activation patterns of immune cells in the brain tumors of mice both under control (isotype) and following anti-PD-1 treatment.}, }
@article {pmid40441587, year = {2025}, author = {Luo, M and Du, Y and Liu, X and Zhang, S and Zhu, W and Liu, K and Ren, X and Zhang, N}, title = {Fecal Microbiota Transplantation Alleviates Cirrhotic Portal Hypertension in Rats via Butyrate-Mediated HDAC3 Inhibition and PI3K/Akt/eNOS Signaling Regulation.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {177781}, doi = {10.1016/j.ejphar.2025.177781}, pmid = {40441587}, issn = {1879-0712}, abstract = {BACKGROUND: Portal hypertension (PHT) is a severe complication of liver cirrhosis, with limited therapeutic options. Despite emerging evidence linking gut microbiota dysbiosis to PHT progression, the mechanisms by which microbial metabolites modulate liver sinusoidal endothelial cells (LSECs) dysfunction and the therapeutic efficacy of fecal microbiota transplantation (FMT) remain poorly understood. This study investigated the potential of FMT to alleviate PHT in cirrhotic rats, exploring the underlying mechanisms involving butyrate-mediated HDAC3 inhibition and PI3K/Akt/eNOS signaling regulation in LSECs.<br><br>METHODS: Cirrhosis with PHT was induced in Sprague-Dawley rats via intraperitoneal carbon tetrachloride injection, followed by FMT or butyrate supplementation via oral gavage. Analyses included portal hemodynamic measurements, gut microbiota sequencing, serum SCFA metabolomics profiling, HDAC3 activity assays, NO level quantification, and assessments of liver fibrosis, liver function, and LSEC ultrastructure. LSECs were isolated for PI3K/Akt/eNOS signaling analysis via qRT-PCR, Western blotting, and immunofluorescence staining.<br><br>RESULTS: A two-week FMT intervention in cirrhotic rats with PHT enriched butyrate-producing bacteria and increased serum butyrate levels, which were associated with reduced portal pressure and intrahepatic vascular resistance, without affecting liver fibrosis, function, or LSEC ultrastructure. FMT reduced HDAC3 activity by 2.17-fold and increased Akt and eNOS phosphorylation in primary LSECs by 1.69-fold and 1.25-fold, respectively, elevating plasma NO levels by 1.66-fold compared to untreated controls. In vitro experiments with primary LSECs confirmed these butyrate-mediated effects.<br><br>CONCLUSION: FMT alleviates cirrhotic PHT through butyrate-mediated HDAC3 inhibition and subsequent PI3K/Akt/eNOS signaling activation in LSECs, highlighting the therapeutic potential of targeting the gut-liver axis via microbial metabolites for PHT management.}, }
@article {pmid40441086, year = {2025}, author = {Sharma, P and Das, S and Rituraj, R and Bhagyashree, B}, title = {Understanding oncobiosis in ovarian cancer: Emerging concepts in tumor progression.}, journal = {Pathology, research and practice}, volume = {271}, number = {}, pages = {156026}, doi = {10.1016/j.prp.2025.156026}, pmid = {40441086}, issn = {1618-0631}, abstract = {Ovarian cancer is a leading cause of gynecologic cancer mortality and has recently been linked to microbial dysbiosis or oncobiosis. Tumorigenesis is a highly complex process, and recent research has revealed numerous new mechanisms showing how tumors interact with their surrounding microenvironment. The inclusion of microbiome studies has significantly advanced this field revealing the important role microbes play, not only in maintaining normal physiological functions of the human body but also in influencing oncogenic pathways. This expanding knowledge is deepening our understanding of tumor pathophysiology and is helping to create new diagnostic, prognostic, therapeutic and preventive strategies for specific cancers. This review explores the role of the microbiome in ovarian carcinogenesis, focusing on its interaction with the tumor microenvironment (TME) and its influence on inflammation, immune regulation and metabolic signaling. This review studied dysbiosis in several anatomical compartments such as the gut, oral cavity, lower and upper genital tracts and ovarian tissues, in relation to ovarian oncobiosis. Emerging clinical implications of these studies include the use of microbial profiles as diagnostic or prognostic biomarkers. Therapeutic strategies such as fecal microbiota transplantation and probiotics are also discussed for their ability to restore microbial balance and enhance treatment efficacy. This review highlights the importance of continued research to explore causal relationships between the microbiome and tumorigenesis, positioning microbiome studies as promising tools in ovarian cancer management and improving patient care.}, }
@article {pmid40438840, year = {2025}, author = {Saleem, MM and Masood, S and Rahmatullah, MM and Ayesha Imdad, I and Mohammed Aslam Sange, A and Nasr, D}, title = {Gut Microbiota Dysbiosis and Its Role in the Development of Irritable Bowel Syndrome.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e83084}, pmid = {40438840}, issn = {2168-8184}, abstract = {The gut microbiota refers to the diverse community of symbiotic and pathogenic microorganisms inhabiting the host digestive tract. This microbiome plays a vital role in maintaining the integrity of the digestive system. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) characterized by chronic abdominal pain and altered bowel habits. Although the pathophysiology of IBS remains unclear, recent studies suggest that the disruption of the gut microbiota (dysbiosis) may play a significant role. This study aims to examine the role of the gut microbiota in the development of IBS, analyze factors influencing the gut microbiome, and explore the potential for microbiota-targeted therapies. Relevant literature published from 2014 until 2024 was sourced from Google Scholar, PubMed, and Scopus using the keywords "microbiome", "irritable bowel syndrome", "dysbiosis", "faecal transplantation", and "probiotics". This review revealed consistent evidence of gut microbiota dysbiosis in individuals with IBS, characterized by altered microbial diversity, composition, and metabolic function. Contributing factors included a reduced abundance of beneficial commensals, overgrowth of potentially pathogenic species, and disrupted host-microbiota interactions. This dysbiosis was also frequently associated with symptom severity and specific IBS subtypes. Emerging evidence further highlights the role of diet, stress, and genetic factors in modulating gut microbiota and influencing IBS development. The growing body of research supports a strong link between dysbiosis and the pathogenesis and symptomatology of IBS. Understanding the microbial underpinnings of IBS opens avenues for potential diagnostic biomarkers and innovative therapeutic interventions aimed at restoring a balanced gut microbiota. However, further research is needed to elucidate the underlying mechanisms and translate these insights into effective clinical strategies for the management of IBS. This review underscores the significance of gut microbiota in IBS and its potential as a target for future therapeutic interventions.}, }
@article {pmid40438215, year = {2025}, author = {Hanna, A and Abbas, H and Yassine, F and AlBush, A and Bilen, M}, title = {Systematic review of gut microbiota composition, metabolic alterations, and the effects of treatments on PCOS and gut microbiota across human and animal studies.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1549499}, pmid = {40438215}, issn = {1664-302X}, abstract = {INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting around 12% of women globally, associated with infertility and various comorbidities. Emerging evidence suggests a crucial role of gut microbiota in PCOS pathophysiology, prompting research to investigate alterations in gut microbial composition in patients with PCOS.<br><br>METHODS: This systematic review aims to analyze human and animal studies that compare gut microbiota composition, gut-derived metabolites, and treatment interventions in PCOS patients versus healthy controls. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, yielding studies examining gut microbiota, metabolomic shifts, and treatment responses in PCOS models and human populations.<br><br>RESULTS: Our analysis revealed decreases in alpha diversity in PCOS patients, with more pronounced changes in beta diversity in animal models. Specific bacterial taxa, such as Bacteroides vulgatus, Escherichia-Shigella and Lactobacillus, showed implication in PCOS pathogenesis, suggesting potential microbial markers. Furthermore, discrepancies between human and animal studies show the need for humanized mouse models to bridge this gap. Interventions like probiotics and fecal microbiota transplantation (FMT) showed varying levels of efficacy, with FMT emerging as a more promising but invasive option, offering live bacteriotherapy as a potential therapeutic alternative. Alterations in gut-derived metabolites, including short-chain fatty acids and bile acids, highlighted the multifaceted nature of PCOS, with implications extending to metabolic, hormonal, and gut-brain axis disruptions.<br><br>DISCUSSION: In conclusion, PCOS exhibits complex interactions between gut microbiota and metabolic pathways, necessitating further research with standardized methods and larger sample sizes to elucidate the microbiome's role in PCOS.}, }
@article {pmid40437401, year = {2025}, author = {Unrug-Bielawska, K and Sandowska-Markiewicz, Z and Pyśniak, K and Piątkowska, M and Czarnowski, P and Goryca, K and Mróz, A and Żeber-Lubecka, N and Wójcik-Trechcińska, U and Bałabas, A and Dąbrowska, M and Surynt, P and Radkiewicz, M and Mikula, M and Ostrowski, J}, title = {Western Diet and fecal microbiota transplantation alter phenotypic, liver fatty acids, and gut metagenomics and metabolomics in Mtarc2 knockout mice.}, journal = {Genes &amp; nutrition}, volume = {20}, number = {1}, pages = {13}, pmid = {40437401}, issn = {1555-8932}, support = {2018/29/B/NZ7/00809//Narodowe Centrum Nauki/ ; }, }
@article {pmid40436727, year = {2025}, author = {Qingsong, L}, title = {Comment on "Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection".}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2025.05.033}, pmid = {40436727}, issn = {0929-6646}, }
@article {pmid40433559, year = {2025}, author = {Zhang, J and Chen, K and Chen, F}, title = {Exploring the impact of the liver-intestine-brain axis on brain function in non-alcoholic fatty liver disease.}, journal = {Journal of pharmaceutical analysis}, volume = {15}, number = {5}, pages = {101077}, pmid = {40433559}, issn = {2214-0883}, abstract = {This study investigates the molecular complexities of non-alcoholic fatty liver disease (NAFLD)-induced brain dysfunction, with a focus on the liver-intestine-brain axis and potential therapeutic interventions. The main objectives include understanding critical microbiota shifts in NAFLD, exploring altered metabolites, and identifying key regulatory molecules influencing brain function. The methods employed encompassed 16S ribosomal RNA (rRNA) sequencing to scrutinize stool microbiota in NAFLD patients and healthy individuals, non-targeted metabolomics using LC-MS to uncover elevated levels of deoxycholic acid (DCA) in NAFLD mice, and single-cell RNA sequencing (scRNA-seq) to pinpoint the pivotal gene Hpgd in microglial cells and its downstream Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Behavioral changes and brain function were assessed in NAFLD mice with and without Fecal microbiota transplantation (FMT) treatment, utilizing various assays and analyses. The results revealed significant differences in microbiota composition, with increased levels of Bacteroides in NAFLD patients. Additionally, elevated DCA levels were observed in NAFLD mice, and FMT treatment demonstrated efficacy in ameliorating liver function and brain dysfunction. Hpgd inhibition by DCA activated the JAK2/STAT3 pathway in microglial cells, leading to inflammatory activation, inhibition of mitochondrial autophagy, induction of neuronal apoptosis, and reduction in neuronal action potentials. This study elucidates the intricate molecular mechanisms underlying the liver-gut-brain axis in NAFLD, and the identification of increased DCA and the impact of JAK2/STAT3 signaling on microglial cells highlight potential therapeutic targets for addressing NAFLD-induced brain dysfunction.}, }
@article {pmid40431274, year = {2025}, author = {Schiavone, N and Isoldi, G and Calcagno, S and Rovida, E and Antiga, E and De Almeida, CV and Lulli, M}, title = {Exploring the Gut Microbiota-Retina Axis: Implications for Health and Disease.}, journal = {Microorganisms}, volume = {13}, number = {5}, pages = {}, doi = {10.3390/microorganisms13051101}, pmid = {40431274}, issn = {2076-2607}, abstract = {The gut microbiota represents a rich and adaptive microbial network inhabiting the gastrointestinal tract, performing key functions in nutrient processing, immune response modulation, intestinal wall protection, and microbial defense. Its composition remains highly personalized and responsive to external influences, including lifestyle patterns, physical activity, body composition, and nutritional intake. The interactions of the gut microbiota with bodily systems are conventionally interpreted as broad systemic impacts on organ balance. Yet, emerging research-exemplified by the gut microbiota-brain axis-suggests the potential existence of more targeted and direct communication mechanisms. Dysbiosis, characterized by microbial ecosystem disturbance, generates multiple metabolic compounds capable of entering systemic circulation and reaching distant tissues, notably including ocular structures. This microbial imbalance has been associated with both systemic and localized conditions linked to eye disorders. Accumulating scientific evidence now supports the concept of a gut-retina axis, underscoring the significant role of microbiota disruption in generating various retinal pathologies. This review comprehensively investigates gut microbiota composition, functional dynamics, and dysbiosis-induced alterations, with specific focus on retinal interactions in age-related macular degeneration, diabetic retinopathy, glaucoma, and retinal artery occlusion. Moreover, the review explores microbiota-targeted therapeutic strategies, including precision nutritional interventions and microbial transplantation, as potential modulators of retinal disease progression.}, }
@article {pmid40431196, year = {2025}, author = {Harder, JW and Ma, J and Collins, J and Alard, P and Jala, VR and Bodduluri, H and Kosiewicz, MM}, title = {Characterization of Sex-Based Differences in Gut Microbiota That Correlate with Suppression of Lupus in Female BWF1 Mice.}, journal = {Microorganisms}, volume = {13}, number = {5}, pages = {}, doi = {10.3390/microorganisms13051023}, pmid = {40431196}, issn = {2076-2607}, support = {Target Identification in Lupus Grant//Alliance for Lupus Research/ ; R01AR067188/NH/NIH HHS/United States ; }, abstract = {Systemic lupus erythematosus (SLE) is more prevalent in female mice and humans and is associated with microbiota dysbiosis. We analyzed the fecal microbiota composition in female and male NZBxNZWF1 (BWF1) mice, a model of SLE, using 16S RNA gene sequencing. Composition of gut microbiota differed between adult disease-prone female (pre-disease) and disease-resistant male mice. Transfer of male cecal contents by gavage into female mice suppressed kidney disease (decreased proteinuria) and improved survival. After our mouse colony was moved to a new barrier facility with similar housing, male cecal transplants failed to suppress disease in female recipients. After two years, the protective phenotype reemerged: male cecal transplants once again suppressed disease in female mice. We compared the gut microbiota composition in female and male BWF1 mice for the three different periods, during which the male microbiota either protected or failed to protect female recipients. In female vs. male mice and in female mice receiving male cecal transplants, we found Bacteroides was high, Clostridium was low (high Bacteroides/Clostridium ratio), and Alistipes was present during periods when male cecal transplants suppressed disease. These data suggest that specific bacterial populations may have opposing effects on disease suppression in a model of microbiota transplantation.}, }
@article {pmid40431182, year = {2025}, author = {Matsumoto, H and Gu, T and Yo, S and Sasahira, M and Monden, S and Ninomiya, T and Osawa, M and Handa, O and Umegaki, E and Shiotani, A}, title = {Fecal Microbiota Transplantation Using Donor Stool Obtained from Exercised Mice Suppresses Colonic Tumor Development Induced by Azoxymethane in High-Fat Diet-Induced Obese Mice.}, journal = {Microorganisms}, volume = {13}, number = {5}, pages = {}, doi = {10.3390/microorganisms13051009}, pmid = {40431182}, issn = {2076-2607}, support = {JP 19K11484//Japanese Grant-in-Aid Scientific Reserach/ ; }, abstract = {The gut microbiota plays an important role in the development of colorectal tumors. However, the underlying mechanisms remain unclear. In this study, we examined the effects of fecal microbiota transplantation (FMT) on azoxymethane (AOM)-induced colorectal tumors in obese mice. We divided the study subjects into the following five groups: high-fat diet (HFD), normal diet (ND), ND+exercise (Ex), HFD+FMT from ND-alone donor (HFD+FMT(ND alone)), and HFD+FMT from ND+Ex donor (HFD+FMT(ND+Ex)). The Ex group performed treadmill exercise for 15 weeks. Thereafter, fecal and colonic mucus samples were extracted for microbiome analysis. The deoxyribonucleic acid sample was collected from the feces and colonic mucosa, and V3-V4 amplicon sequencing analysis of the 16S rRNA gene was performed using MiSeq. The number of polyps was significantly lower in the ND (6.0 ± 1.6) and ND+Ex (1.8 ± 1.3) groups than in the HFD group (11.4 ± 1.5). The ND+Ex group had significantly fewer polyps than the ND group. The HFD+FMT(ND alone) (5.2 ± 0.8) and HFD+FMT(ND+Ex) (2.8 ± 2.6) groups also had significantly fewer polyps than the HFD group. The IL-15 mRNA levels in the colonic tissues were significantly higher in the HFD+FMT(ND alone) group than in the ND group. Fecal ω-muricholic acid concentrations were significantly higher in the HFD+FMT(ND alone) group than in the ND group and in the HFD+FMT(ND+Ex) group than in the ND+Ex group. The ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of Lacyobacillaceae than the HFD group. In the FMT group, Erysipelotrichaceae and Tannerellaceae were significantly less abundant. Compared with the HFD group, the ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of Muribaculaceae and a significantly higher abundance of Lactobacillaceae and Rikenellaceae in common among the ND and ND+Ex groups. The common and significantly less common species were Bacteroidaceae in the FMT group and Lactobacillaceae and Rikenellaceae in the ND alone and ND+Ex groups. Bacteroidaceae and Lachnospiraceae were significantly less common in the FMT group. We found that FMT inhibited AOM-induced colorectal tumorigenesis in obese mice. Furthermore, the fecal concentrations of short-chain fatty acids, bile acids, microbiota, and mucosa-associated microbiota differed between the FMT and diet/EX groups, suggesting that the inhibitory effect of FMT on colorectal tumorigenesis may be due to mechanisms different from those of ND alone and ND+Ex.}, }
@article {pmid40430481, year = {2025}, author = {Zhou, Q and Yang, C and Jia, M and Qu, Q and Peng, X and Ren, W and Li, G and Xie, Y and Li, B and Shi, X}, title = {Gut Microbiota-Targeted Intervention of Hyperlipidemia Using Monascus-Fermented Ginseng.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {5}, pages = {}, doi = {10.3390/ph18050661}, pmid = {40430481}, issn = {1424-8247}, support = {82174093//National Natural Science Foundation of China/ ; }, abstract = {Background/Objectives: Hyperlipidemia (HLP) encompasses a spectrum of poorly understood lipid metabolism disorders that are frequently overlooked or misdiagnosed, potentially leading to multiple complications. While the gut microbiota has been implicated in HLP pathogenesis, the causal relationships and molecular mechanisms remain elusive. This study aimed to investigate the therapeutic mechanisms of Monascus-fermented ginseng (MFG) on HLP through gut microbiota modulation and explore treatment potential via fecal microbiota transplantation (FMT). Methods: The MFG-modulated gut microbiota was transplanted into HLP mice. Systemic evaluations, including serum biochemical parameter detection, histopathological section analysis, 16S rRNA sequencing, and fecal metabolomics, were conducted to assess therapeutic efficacy and identify associated metabolic pathways. Results: FMT significantly improved lipid profiles, reduced body weight, and attenuated hepatic lipid accumulation in HLP mice. Mechanistically, it enhanced cholesterol excretion and fatty acid β-oxidation while suppressing lipogenic regulators, concurrently promoting primary-to-secondary bile acid conversion. Gut microbiota analysis revealed that the MFG intervention effectively normalized the Firmicutes/Bacteroidetes ratio and enriched beneficial microbiota. Conclusions: These findings demonstrate FMT's therapeutic value in HLP management and provide new perspectives on utilizing fermented herbal medicines for metabolic disorders via gut microbiota reprogramming.}, }
@article {pmid40428769, year = {2025}, author = {Datkhayeva, Z and Iskakova, A and Mireeva, A and Seitaliyeva, A and Skakova, R and Kulniyazova, G and Shayakhmetova, A and Koshkimbayeva, G and Sarmuldayeva, C and Nurseitova, L and Koshenova, L and Imanbekova, G and Maxutova, D and Yerkenova, S and Shukirbayeva, A and Pernebekova, U and Dushimova, Z and Amirkhanova, A}, title = {The Multifactorial Pathogenesis of Endometriosis: A Narrative Review Integrating Hormonal, Immune, and Microbiome Aspects.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {5}, pages = {}, doi = {10.3390/medicina61050811}, pmid = {40428769}, issn = {1648-9144}, mesh = {Humans ; *Endometriosis/physiopathology/microbiology/immunology/etiology ; Female ; *Gastrointestinal Microbiome/physiology/immunology ; Estrogens/metabolism ; Dysbiosis/complications ; Inflammation ; }, abstract = {Endometriosis (EM) is a common estrogen-dependent chronic inflammatory disorder affecting reproductive-aged women, yet its pathogenesis remains incompletely understood. Recent evidence suggests that the gut microbiota significantly influence immune responses, estrogen metabolism, and systemic inflammation, potentially contributing to EM progression. This narrative review explores the relationship between the gut microbiota and EM, emphasizing microbial dysbiosis, inflammation, estrogen regulation, and potential microbiome-targeted therapies. Studies published within the last 30 years were included, focusing on the microbiota composition, immune modulation, estrogen metabolism, and therapeutic interventions in EM. The selection criteria prioritized peer-reviewed articles, clinical trials, meta-analyses, and narrative reviews investigating the gut microbiota's role in EM pathophysiology and treatment. Microbial dysbiosis in EM is characterized by a reduced abundance of beneficial bacteria (Lactobacillus, Bifidobacterium, and Ruminococcaceae) and an increased prevalence of pro-inflammatory taxa (Escherichia/Shigella, Streptococcus, and Bacteroides). The gut microbiota modulate estrogen metabolism via the estrobolome, contributing to increased systemic estrogen levels and lesion proliferation. Additionally, lipopolysaccharides (LPS) from Gram-negative bacteria activate the TLR4/NF-κB signaling pathway, exacerbating inflammation and EM symptoms. The interaction between the gut microbiota, immune dysregulation, and estrogen metabolism suggests a critical role in EM pathogenesis. While microbiota-targeted interventions offer potential therapeutic benefits, further large-scale, multi-center studies are needed to validate microbial biomarkers and optimize microbiome-based therapies for EM. Integrating microbiome research with precision medicine may enhance the diagnostic accuracy and improve the EM treatment efficacy.}, }
@article {pmid40427529, year = {2025}, author = {Daude, N and Machado, I and Arce, L and Yang, J and Westaway, D}, title = {Microbial Composition, Disease Trajectory and Genetic Background in a Slow Onset Model of Frontotemporal Lobar Degeneration.}, journal = {Biomolecules}, volume = {15}, number = {5}, pages = {}, doi = {10.3390/biom15050636}, pmid = {40427529}, issn = {2218-273X}, support = {N/A//Nanostring AD panel/ ; N/A//SynAD ADRD/ ; 16308/CAPMC/CIHR/Canada ; 173286/CAPMC/CIHR/Canada ; NIF 21633//Canada Foundation for Innovation/ ; NIF 39588//Canada Foundation for Innovation/ ; N/A//Campus Alberta Neuroscience/ ; APRIIEP201600033//Alberta Prion Research Institute/ ; N/A//Hope for Tomorrow/ ; }, mesh = {Animals ; Mice ; Mice, Transgenic ; Disease Models, Animal ; tau Proteins/metabolism/genetics ; *Frontotemporal Lobar Degeneration/genetics/microbiology/pathology/metabolism ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome/genetics ; Genetic Background ; Humans ; Male ; }, abstract = {Slow-onset neurodegenerative disease in a low-expresser 2N4R P301L transgenic (Tg) mouse model is marked by neuroinflammation and by differing patterns of CNS deposition and accumulation of tau conformers, with such heterogeneities present even within inbred backgrounds. Gut microbial genotypes were notably divergent within C57BL6/Tac or 129SvEv/Tac congenic (Cg) sublines of TgTau[P301L] mice, and these sublines differed when challenged with antibiotic treatment and fecal microbial transplantation. Whereas aged, transplanted Cg 129SvEv/Tac TgTau[P301L] mice had neuroanatomical deposition of tau resembling controls, transplanted Cg C57BL6/Tac TgTau[P301L] mice had different proportions of rostral versus caudal tau accumulation (p = 0.0001). These data indicate the potential for environmental influences on tau neuropathology in this model. Furthermore, Cg C57BL6/Tac TgTau[P301L] cohorts differed from 129SvEv/Tac counterparts by showing 28% versus 9% net intercurrent loss (p = 0.0027). While the origin of this phenomenon is not established, it offers a parallel to differing patterns of frailty observed in C57BL6 versus 129 SvEv Tg mice expressing the 695 amino acid isoform of human amyloid precursor protein. We infer that generalized responses to protein aggregation might account for similar reductions in viability even when expressing different human proteins in the same inbred strain background.}, }
@article {pmid40427424, year = {2025}, author = {Golenia, A and Olejnik, P}, title = {The Role of Oxidative Stress in Ischaemic Stroke and the Influence of Gut Microbiota.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {5}, pages = {}, doi = {10.3390/antiox14050542}, pmid = {40427424}, issn = {2076-3921}, abstract = {Ischaemic stroke is the most prevalent stroke subtype, accounting for 80-90% of all cases worldwide, and remains a leading cause of morbidity and mortality. Its pathophysiology involves complex molecular cascades, with oxidative stress playing a central role. During cerebral ischaemia, reduced blood flow deprives neurons of essential oxygen and nutrients, triggering excitotoxicity, mitochondrial dysfunction, and excessive production of reactive oxygen and nitrogen species (RONS). Not only do these species damage cellular components, but they also activate inflammatory pathways, particularly those mediated by the transcription factor nuclear factor kappa-B (NF-κB). The pro-inflammatory milieu intensifies neuronal damage, compromises blood-brain barrier integrity, and exacerbates reperfusion-induced damage. Recent findings highlight the importance of the gut microbiota in modulating stroke outcomes, primarily through metabolic and immunological interactions along the gut-brain axis. Dysbiosis, characterised by reduced microbial diversity and an imbalance between beneficial and harmful strains, has been linked to increased systemic inflammation, oxidative stress, and worse prognoses. Specific gut-derived metabolites, including short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO), appear to either mitigate or intensify neuronal injury. SCFAs may strengthen the blood-brain barrier and temper inflammatory responses, whereas elevated TMAO levels may increase thrombotic risk. This narrative review consolidates both experimental and clinical data demonstrating the central role of oxidative stress in ischaemic stroke pathophysiology and explores the gut microbiota's ability to modulate these damaging processes. Therapeutic strategies targeting oxidative pathways or rebalancing gut microbial composition, such as antioxidant supplementation, dietary modulation, probiotics, and faecal microbiota transplantation, present promising paradigms for stroke intervention. However, their widespread clinical implementation is hindered by a lack of large-scale, randomised trials. Future efforts should employ a multidisciplinary approach to elucidate the intricate mechanisms linking oxidative stress and gut dysbiosis to ischaemic stroke, thereby paving the way for novel, mechanism-based therapies for improved patient outcomes.}, }
@article {pmid40426604, year = {2025}, author = {Xia, YM and Zhang, MX and Ma, XY and Tan, LL and Li, T and Wu, J and Li, MA and Zhao, WJ and Qiao, CM and Jia, XB and Shen, YQ and Cui, C}, title = {Intranasal Transplantation of Microbiota Derived from Parkinson's Disease Mice Induced Astrocyte Activation and Neurodegenerative Pathology from Nose to Brain.}, journal = {Brain sciences}, volume = {15}, number = {5}, pages = {}, doi = {10.3390/brainsci15050433}, pmid = {40426604}, issn = {2076-3425}, support = {82171429//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Parkinson's disease (PD) is characterized by early-onset olfactory dysfunction preceding motor symptoms, yet its mechanisms remain elusive. Based on the studies on microbiota-gut-brain axis, the microbiota-nose-brain axis might be involved in the pathogenesis of PD. However relative studies are rare.<br><br>METHODS: By consecutive 14-days intranasally transplanting bacteria, we established mice models exhibiting nasal microbiota dysbiosis (NMD), including animal group received intranasal drops of fecal bacterial suspension from normal mice (NB group) and animal group received intranasal drops of fecal bacterial suspension from PD mice (PB group), with animals that only received anesthesia used as the control group. Then we analyzed the nasal microbiota composition via 16S rRNA sequencing, evaluated the olfactory and motor functions through behavioral experiments, including buried food test, open field test, pole descent test, and traction test. The neuropathology in olfactory-related and PD-related brain regions, including olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum, was also detected by western blotting, immunofluorescence and immunohistochemical experiments using the antibodies of NeuN, TH and GFAP.<br><br>RESULTS: 16S rRNA sequencing revealed that PB mice were primarily characterized by an increase in bacteria associated with inflammation and PD. Behavioral assessments revealed that mice with NMD demonstrated impairments in the buried food test and pole descent test, indicative of olfactory and motor dysfunction. By detecting NeuN and GFAP expression, we identified neuronal loss and astrocytes activation in olfactory-related brain regions and adjacent structures, including the olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum of both NMD groups, which may contribute to the observed functional disorders. Notably, animals exposed to PD-derived bacteria exhibited more pronounced changes in nasal bacteria, with more severe neuropathology.<br><br>CONCLUSIONS: We present evidence supporting the microbiota-nose-brain axis, and the NMD-induced astrocyte activation and neurodegenerative pathology along the olfactory pathway may serve as a link between nose and brain.}, }
@article {pmid40424882, year = {2025}, author = {Huang, YY and Qin, SM and Nguyen, MT and Chen, W and Si, XM and Huang, YQ and Zhang, HY}, title = {The protective effects of dietary resistant starch against post-antibiotic bone loss in meat ducks associated with the recovery of caecal microbiota dysbiosis.}, journal = {Poultry science}, volume = {104}, number = {8}, pages = {105238}, doi = {10.1016/j.psj.2025.105238}, pmid = {40424882}, issn = {1525-3171}, abstract = {Compromised bone quality increases the risk of fractures in domesticate birds, resulting in pain and altered behaviour. Although dietary resistant starch (RS) supplementation show promise for improving inferior bone mass, the diet-mediated gut microbiota alterations as a potential mechanism underlying RS positive roles in bone remains uncertain. With a post-antibiotic model and faecal microbiota transplantation (FMT), this study investigated the effects of a RS diet on antibiotic-induced bone loss and gut microbial composition in meat ducks. Ducklings were assigned to 4 treatments with 6 replicate pens until 21 d, including the control group (Ctrl, feeding a basal diet) and the RS-fed group, and post-antibiotic treatment following the gavage of phosphate-buffered saline (Post-anti-PBS) or faecal microbiota transplantation (Post-anti-FMT). The RS diet increased the proportion of Firmicutes, improved intestinal integrity, and reduced inflammation-induced bone resorption, all of which contributed to an increase in tibial bone volume (P < 0.05). Post-antibiotic treatment was found to reduce tibial quality by stimulating bone resorption and inhibiting bone formation, accompanied by gut microbiota dysbiosis, increased intestinal permeability (P = 0.059), and inflammatory flare compared to control birds. FMT from RS-fed ducks into the antibiotic-treated birds reversed bone loss by primarily blocking osteoclastic frequency and activity. Furthermore, FMT increased the ratio of Firmicutes to Bacteroidetes (P < 0.05) and suppressed the release of pro-osteoclastogenic cytokines such as tumour necrosis factor-α (P = 0.062) and interleukin-1β (P < 0.05) in the bone marrow. These results demonstrated the involvement of gut microbiota in improving bone quality of meat ducks by RS, and FMT of RS-fed birds corrected the imbalance of ceca microbiota and attenuated bone loss in meat ducks with enhanced bone resorption.}, }
@article {pmid40335381, year = {2025}, author = {Vuyk, W and Bobholz, M and Emmen, I and Lail, A and Minor, N and Bhimalli, P and Eickhoff, JC and Ries, HJ and Machkovech, H and Wei, W and Weiler, A and Richardson, A and DePagter, C and VanSleet, G and Bhasin, M and Kamal, S and Wolf, S and Virdi, A and Bradley, T and Gifford, A and Benito, M and Shipe, A and Mohamed, R and Smith, J and Wilson, N and Friedrich, TC and O'Connor, DH and Garonzik-Wang, J}, title = {Longitudinal Assessment of Solid Organ Transplant Recipients With SARS-CoV-2 Infection.}, journal = {Transplantation proceedings}, volume = {57}, number = {5}, pages = {922-930}, doi = {10.1016/j.transproceed.2025.04.004}, pmid = {40335381}, issn = {1873-2623}, mesh = {Humans ; *COVID-19/diagnosis/virology/epidemiology/immunology ; Middle Aged ; *SARS-CoV-2/genetics/isolation &amp; purification ; Male ; *Organ Transplantation/adverse effects ; *Immunocompromised Host ; Female ; Virus Shedding ; *Transplant Recipients ; Prospective Studies ; Adult ; RNA, Viral ; Longitudinal Studies ; Viral Load ; Aged ; Feces/virology ; }, abstract = {BACKGROUND: Compared with immunocompetent individuals, those who are immunocompromised, including solid organ transplant (SOT) recipients, have higher SARS-CoV-2-related morbidity and mortality. We determined the duration of SARS-CoV-2 RNA positivity to evaluate viral persistence in SOT recipients.<br><br>METHODS: This study prospectively followed SOT recipients who recently tested positive for SARS-CoV-2. The duration of viral RNA shedding in nasal swabs and stool samples was tracked, and viral genome sequencing was performed where possible. Persistent infection was defined as a positive nucleic acid amplification test (NAAT) for SARS-CoV-2 at 28 days or later after initial infection. This duration was chosen based on the U.S. Centers for Disease Control and Prevention (CDC) recommendation that immunocompromised individuals isolate for at least 20 days [1], compared with 10 days for non-immunocompromised individuals.<br><br>RESULTS: Of 30 SOT recipients, 12 (40%) had positive SARS-CoV-2 RNA in nasal swabs or stool (cycle threshold [Ct] < 40) at 28 or more days after the first positive SARS-CoV-2 test. Immunocompromised (IC) subject 015 had high viral loads (Ct < 30) at 28 days, with continued detection for 54 days.<br><br>CONCLUSIONS: In 12 of 30 SOT subjects, SARS-CoV-2 RNA was detected at or beyond 28 days post-detection (dpd), despite vaccination and antibody and/or antiviral treatment in most participants. Three subjects tested positive for SARS-CoV-2 RNA past 50 dpd. Viral persistence in the setting of host immune suppression, coupled with exposure to antiviral treatments, raises concern about the selection of unusual viral variants.}, }
@article {pmid40422666, year = {2025}, author = {Gaspar, BS and Roşu, OA and Enache, RM and Manciulea Profir, M and Pavelescu, LA and Creţoiu, SM}, title = {Gut Mycobiome: Latest Findings and Current Knowledge Regarding Its Significance in Human Health and Disease.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, doi = {10.3390/jof11050333}, pmid = {40422666}, issn = {2309-608X}, abstract = {The gut mycobiome, the fungal component of the gut microbiota, plays a crucial role in health and disease. Although fungi represent a small fraction of the gut ecosystem, they influence immune responses, gut homeostasis, and disease progression. The mycobiome's composition varies with age, diet, and host factors, and its imbalance has been linked to conditions such as inflammatory bowel disease (IBD) and metabolic disorders. Advances in sequencing have expanded our understanding of gut fungi, but challenges remain due to methodological limitations and high variability between individuals. Emerging therapeutic strategies, including antifungals, probiotics, fecal microbiota transplantation, and dietary interventions, show promise but require further study. This review highlights recent discoveries on the gut mycobiome, its interactions with bacteria, its role in disease, and potential clinical applications. A deeper understanding of fungal contributions to gut health will help develop targeted microbiome-based therapies.}, }
@article {pmid40421334, year = {2025}, author = {Ponce Alencastro, JA and Salinas Lucero, DA and Solis, RP and Herrera Giron, CG and Estrella López, AS and Anda Suárez, PX}, title = {Molecular Mechanisms and Emerging Precision Therapeutics in the Gut Microbiota-Cardiovascular Axis.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e83022}, pmid = {40421334}, issn = {2168-8184}, abstract = {A microbiome in the gut plays a significant role in cardiovascular health and disease. Dysbiosis is an imbalance in the gut microbiome, leading to multiple cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and heart failure. Gut microbe-derived metabolites such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs) are important mediators of the gut-heart axis. Evaluation of the relationship between the gut microbiome and host biomarkers with CVD requires the integration of metagenomics and metabolomics with meta-omics approaches. The literature review found that microbes and metabolic signatures are associated with the risk and progression of CVD. The development of precision therapeutic approaches for targeting gut microbiota includes preventing adverse microbial effects using probiotics, prebiotics, and the drug-as-bug approach to inhibit harmful metabolites of microbiomes, and fecal microbiota transplantation (FMT). However, the implication and practice of these findings in clinical settings face challenges due to the heterogeneity of study designs, difficulty in the determination of causality, and the impact of confounding factors such as diet, medication, and potential inter-individual gut microbiome variability. Future researchers are recommended to conduct longitudinal studies to further establish both gut microbiome associations with CVD and develop successful precision therapeutics approaches based on the microbiome for the treatment of CVD.}, }
@article {pmid40420583, year = {2025}, author = {He, X and Luthuli, S and Wen, Q and Wang, C and Ding, J and Cui, B and Zhang, F}, title = {Washed microbiota transplantation for ribotype 027 Clostridioides difficile infection in a pregnant woman with two-year follow-up: a case report.}, journal = {Journal of biomedical research}, volume = {}, number = {}, pages = {1-4}, doi = {10.7555/JBR.39.20250063}, pmid = {40420583}, issn = {1674-8301}, abstract = {Clostridioides difficile (C. difficile) is one of the major causes of nosocomial infections. The pregnant women, who were considered at low risk for C. difficile infection (CDI), have attracted attention with increasing reports. Oral vancomycin, the only first-line treatment for the pregnant women infected with C. difficile, came with the problem of increasing strains resistance that was associated with decreased efficacy. Fecal microbiota transplantation (FMT) is recommended for severe, fulminant and recurrent CDI, while it is avoided in the pregnant women due to safety concerns. We reported a pregnant woman case with primary ribotype 027 CDI, who got a successful outcome with washed microbiota transplantation (WMT), an improved FMT, via enema. The specific strain of ribotype 027 was related to severe outcomes but was not reported in the pregnant women. The follow-up lasted two years, the patient's diarrhea was fully alleviated without recurrence. The baby had normal growth and development and no adverse events were recorded in both of them. This case provides evidence for the efficacy and safety of WMT in the pregnant women infected with C. difficile, indicating that WMT via enema may be a strategy for this population in treating CDI.}, }
@article {pmid40419682, year = {2025}, author = {Nishinarita, Y and Miyoshi, J and Kuronuma, S and Wada, H and Oguri, N and Hibi, N and Takeuchi, O and Akimoto, Y and Lee, STM and Matsuura, M and Kobayashi, T and Hibi, T and Hisamatsu, T}, title = {Characteristic gene expression profile of intestinal mucosa early in life promotes bacterial colonization leading to healthy development of the intestinal environment.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {18437}, pmid = {40419682}, issn = {2045-2322}, support = {19K23977//Japan Society for the Promotion of Science/ ; 21K07900//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/genetics ; Mice ; *Intestinal Mucosa/microbiology/metabolism ; Fecal Microbiota Transplantation ; *Bacteria/genetics/growth &amp; development/classification ; Germ-Free Life ; *Transcriptome ; Male ; Gene Expression Profiling ; Female ; Feces/microbiology ; Mice, Inbred C57BL ; }, abstract = {The gut microbiome early in life plays a crucial role in development of the host and affects health throughout life. The definition of a healthy microbiome early in life has not been established, and the underlying mechanism of how a young host selects appropriate microbes for colonization remains unclear. Understanding the mechanism may provide insights into novel preventive and therapeutic strategies by correcting dysbiosis early in life. We employed germ-free mice early in life (4 weeks of age) and later in life (10 weeks of age) for fecal microbiota transfer (FMT) from specific pathogen-free mice. We performed age-unmatched FMT between recipients early in life and donors early or later in life, in addition to common age-matched FMT. Age-matched FMT resulted in significantly different bacterial compositions between recipients early vs. later in life. When the gut microbiome from donors early or later in life was transferred to recipients early in life, bacterial compositions of recipients from donors later in life were similar to those of recipients from donors early in life. This finding suggests that the host early in life has mechanisms to select microbes appropriate for age from the exposed microbiome. We hypothesized that the age-specific intestinal environment promotes age-appropriate intestinal microbiome colonization and examined gene expression in the intestinal mucosa of germ-free mice. We observed that gene expression profiles were different between early vs. later in life. Correlation analysis demonstrated that genera Lachnospiraceae NK4A136 group and Roseburia were positively correlated to genes expressed predominantly early in life, but negatively with genes expressed predominantly later in life. We confirmed that the relative abundance of these genera was significantly higher in specific pathogen-free mice early in life compared with mice later in life. The characteristic gene expression of the intestinal mucosa early in life might play roles in selecting specific bacteria in the intestinal microbiome early in life.}, }
@article {pmid40419041, year = {2025}, author = {Chen, L and Zhao, S and Chen, Q and Luo, P and Li, X and Song, Y and Pan, S and Wu, Q and Zhang, Y and Shen, X and Chen, Y}, title = {Poria cocos polysaccharides ameliorate AOM/DSS-induced colorectal cancer in mice by remodeling intestinal microbiota composition and enhancing intestinal barrier function.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {144477}, doi = {10.1016/j.ijbiomac.2025.144477}, pmid = {40419041}, issn = {1879-0003}, abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the development of novel therapeutic strategies. Poria cocos polysaccharides (PCP), bioactive components of the traditional medicinal fungus Poria cocos, exhibit significant anticancer potential. This study investigates the protective effects of PCP against azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC in mice, with a focus on its impact on intestinal microbiota composition, intestinal barrier integrity, and inflammatory responses. PCP treatment significantly reduced tumor incidence, tumor size, and tumor burden while improving histopathological features and inhibiting Ki67-positive cell proliferation. Mechanistically, PCP enhanced intestinal barrier function by restoring tight junction proteins (E-cadherin, ZO-1, Claudin-3) and mucin secretion (MUC2), thereby reducing intestinal permeability and systemic lipopolysaccharide (LPS) levels. Furthermore, PCP exhibited potent anti-inflammatory effects by downregulating pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and upregulating the anti-inflammatory cytokine IL-10. 16S rRNA sequencing results revealed that PCP modulated the intestinal microbiota, decreasing pathogenic bacteria such as Helicobacter and Eisenbergiella while promoting beneficial taxa including Limosilactobacillus, Paraprevotella, and Muribaculum. Fecal microbiota transplantation (FMT) further confirmed the microbiota-mediated protective effects of PCP, as FMT from PCP-treated donors significantly suppressed tumorigenesis, restored intestinal barrier integrity, and alleviated inflammation in CRC mice. Additionally, PCP demonstrated a favorable safety profile, with no adverse effects on major organs. These findings highlight PCP as promising natural agents for CRC prevention and therapy, acting through modulation of the intestinal microbiota, enhancement of intestinal barrier function, and suppression of inflammation.}, }
@article {pmid40415934, year = {2025}, author = {Liu, L and Zhao, W and Zhang, H and Shang, Y and Huang, W and Cheng, Q}, title = {Relationship between pediatric asthma and respiratory microbiota, intestinal microbiota: a narrative review.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1550783}, pmid = {40415934}, issn = {1664-302X}, abstract = {Pediatric asthma is a common chronic airway inflammatory disease that begins in childhood and its impact persists throughout all age stages of patients. With the continuous progress of detection technologies, numerous studies have firmly demonstrated that gut microbiota and respiratory microbiota are closely related to the occurrence and development of asthma, and related research is increasing day by day. This article elaborates in detail on the characteristics, composition of normal gut microbiota and lung microbiota at different ages and in different sites, as well as the connection of the gut-lung axis. Subsequently, it deeply analyzes various factors influencing microbiota colonization, including host factor, delivery mode, maternal dietary and infant feeding patterns, environmental microbial exposure and pollutants, and the use of antibiotics in early life. These factors are highly likely to play a crucial role in the onset process and disease progression of asthma. Research shows that obvious changes have occurred in the respiratory and gut microbiota of asthma patients, and these microbiomes exhibit different characteristics according to the phenotypes and endotypes of asthma. Finally, the article summarizes the microbiota-related treatment approaches for asthma carried out in recent years, including the application of probiotics, nutritional interventions, and fecal microbiota transplantation. These treatment modalities are expected to become new directions for future asthma treatment and bring new hope for solving the problem of childhood asthma.}, }
@article {pmid40415928, year = {2025}, author = {Karimianghadim, R and Satokari, R and Yeo, S and Arkkila, P and Kao, D and Pakpour, S}, title = {Prolonged effect of antibiotic therapy on the gut microbiota composition, functionality, and antibiotic resistance genes' profiles in healthy stool donors.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1589704}, pmid = {40415928}, issn = {1664-302X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is highly effective in preventing Clostridioides difficile recurrence by restoring gut microbiota composition and function. However, the impact of recent antibiotic use, a key exclusion criterion for stool donors, on gut microbiota recovery is poorly understood.<br><br>METHODS: We investigated microbial recovery dynamics following antibiotic use in three long-term stool donors from Canada and Finland. Using longitudinal stool sampling, metagenomic sequencing, and qPCR, we assessed changes in bacterial diversity, community composition, microbial functions, the gut phageome, and the risk of transmitting antibiotic-resistant genes (ARGs).<br><br>RESULTS: Antibiotics caused lasting disruption to bacterial communities, significantly reducing important taxa like Bifidobacterium bifidum, Blautia wexlerae, Akkermansia muciniphila, Eubacterium sp. CAG 180, and Eubacterium hallii, with effects persisting for months. Functional analyses revealed alterations in housekeeping genes critical for energy production and biosynthesis, with no direct links to key health-related pathways. Antibiotics also disrupted viral populations, decreasing diversity and increasing crAssphage abundance, reflecting disrupted host-bacteriophage dynamics. No significant increase in clinically important ARGs was detected.<br><br>DISCUSSION: These findings highlight the unpredictable and complex recovery of gut microbiota post-antibiotics. Individualized suspension periods in donor programs, guided by metagenomic analyses, are recommended to optimize FMT outcomes in various indications by considering antibiotic spectrum, duration, and host-specific factors.}, }
@article {pmid40414934, year = {2025}, author = {Jan, A and Bayle, P and Mohellibi, N and Lemoine, C and Pepke, F and Béguet-Crespel, F and Jouanin, I and Tremblay-Franco, M and Laroche, B and Serror, P and Rigottier-Gois, L}, title = {A consortium of seven commensal bacteria promotes gut microbiota recovery and strengthens ecological barrier against vancomycin-resistant enterococci.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {129}, pmid = {40414934}, issn = {2049-2618}, support = {COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; PhD scholarship AJ (2020-2023)//INRAE Metaprogram HOLOFLUX and doctoral school ABIES at University Paris-Saclay/ ; Travel grants from Graduate schools Life sciences and Health (LSH) and Biosphera from University Paris-Saclay//France 2030 program "ANR-11-IDEX-0003"/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; Key action MIND (2017)//INRAE Metaprogram MEM/ ; Key action MIND (2017)//INRAE Metaprogram MEM/ ; Key action MIND (2017)//INRAE Metaprogram MEM/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Vancomycin-Resistant Enterococci/growth &amp; development ; Mice ; Symbiosis ; Dysbiosis/microbiology/chemically induced ; Anti-Bacterial Agents ; *Gram-Positive Bacterial Infections/microbiology ; Feces/microbiology ; *Bacteria/classification/genetics/isolation &amp; purification ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Vancomycin-resistant enterococci (VRE) often originate from the gastrointestinal tract, where their proliferation precedes dissemination into the bloodstream, and can lead to systemic infection. Uncovering the actors and mechanisms reducing the intestinal colonisation by VRE is essential to control infection. We aimed to identify commensal bacteria that interfere with VRE gut colonisation or act as an ecological barrier.<br><br>RESULTS: We performed a 3-week longitudinal analysis of the gut microbiota composition and VRE carriage levels during microbiota recovery in mice colonised with VRE after antibiotic-induced dysbiosis. By combining biological data and mathematical modelling, we identified 15 molecular species (OTUs) that negatively correlated with VRE overgrowth. Six strains representative of these OTUs were collected, cultivated and used in mixture with a seventh strain (Mix7) in two different mouse lines challenged with VRE. Of the seven strains, three belonged to Lachnospiraceae, one to Muribaculaceae, one to Ruminococcaceae and two to Lactobacillaceae. We found that Mix7 led to a better recovery of the gut microbiota composition and reduced VRE carriage. Differences in the effect of Mix7 were observed between responder and non-responder mice. These differences were associated with variations in the composition of the initial microbiota and during recovery and represent potential biomarkers for predicting response to Mix7. In a mouse model of alternative stable state of dysbiosis, response to Mix7 was associated with higher concentrations of short-chain fatty acids (acetate, propionate, butyrate) and a range of metabolites including bile acids, reflecting the recovery of the microbiota back to initial state. Furthermore, Muribaculum intestinale strain was required to obtain the Mix7 effect on VRE reduction in vivo, but the presence of at least one of the other six strains was needed. None of the supernatant of the seven strains, alone or in combination, inhibited VRE growth in vitro. Interestingly, five strains belong to species shared among humans and mice, and the other two have human functional equivalents.<br><br>CONCLUSIONS: An innovative approach based on mathematical modelling of the microbiota composition permitted to identify a mixture of commensal bacterial strains, which improves the ecological barrier effect against VRE. The mechanisms are dependent on the recovery and initial composition of the microbiota. Ultimately, this work will enable a move towards a personalised medicine by targeting predisposed patients presenting a risk of infection, such as neutropenic or bone-marrow transplant patients, and likely to respond to supplementation with commensal strains, providing new live biotherapeutic products and biomarkers to predict response to supplementation. Video Abstract.}, }
@article {pmid40414635, year = {2025}, author = {Kumar, R and Kumar, R}, title = {Intestinal dysbiosis leads to the reduction in neurochemical production in Parkinson's disease (PD).}, journal = {International review of neurobiology}, volume = {180}, number = {}, pages = {25-56}, doi = {10.1016/bs.irn.2025.03.004}, pmid = {40414635}, issn = {2162-5514}, mesh = {Humans ; *Dysbiosis/metabolism/therapy ; *Parkinson Disease/metabolism/therapy/physiopathology/microbiology ; *Gastrointestinal Microbiome/physiology ; Animals ; }, abstract = {Parkinson's Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, with emerging research suggesting a critical link between intestinal dysbiosis and PD progression. This review explores the pathophysiological mechanisms underlying PD, such as alpha-synuclein aggregation, mitochondrial dysfunction, neuroinflammation, and oxidative stress, while focusing on the impact of gut dysbiosis on intestinal barrier function and its role in reduced neurochemical production. The clinical features of PD, including dopamine, serotonin, and GABA deficiencies, are examined, with a focus on how dysbiosis contributes to neurotransmitter depletion. Current treatments of PD, such as levodopa and dopamine agonists, are discussed alongside gut health therapies such as probiotics, prebiotics, and Fecal Microbiota Transplantation (FMT). Future therapeutic directions, including synbiotics, engineered microbes, phage therapy, and the integration of machine learning (ML) and artificial intelligence (AI), are explored. The chapter also considers preventive strategies, such as lifestyle adjustments and early gut health monitoring using modern diagnostic tools and biosensors. Furthermore, a strong need for continued research into the gut-brain axis (GBA) to develop more effective, gut-targeted therapies for managing PD is discussed.}, }
@article {pmid40414634, year = {2025}, author = {Singh, S and Saini, V and Jha, HC}, title = {The role of secondary genomes in neurodevelopment and co-evolutionary dynamics.}, journal = {International review of neurobiology}, volume = {180}, number = {}, pages = {245-297}, doi = {10.1016/bs.irn.2025.03.008}, pmid = {40414634}, issn = {2162-5514}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodevelopmental Disorders/genetics/microbiology ; *Biological Evolution ; Animals ; *Brain/growth &amp; development ; }, abstract = {This chapter examines how human biology and microbial "secondary genomes" have co-evolved to shape neurodevelopment through the gut-brain axis. Microbial communities generate metabolites that cross blood-brain and placental barriers, influencing synaptogenesis, immune responses, and neural circuit formation. Simultaneously, Human Accelerated Regions (HARs) and Endogenous Retroviruses (ERVs) modulate gene expression and immune pathways, determining which microbes thrive in the gut and impacting brain maturation. These factors converge to form a dynamic host-microbe dialogue with significant consequences for neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia. Building on evolutionary perspectives, the chapter elucidates how genetic and immune mechanisms orchestrate beneficial and pathological host-microbe interactions in early brain development. It then explores therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation, and CRISPR-driven microbial engineering, targeting gut dysbiosis to mitigate or prevent neurodevelopmental dysfunctions. Furthermore, innovative organ-on-chip models reveal mechanistic insights under physiologically relevant conditions, offering a translational bridge between in vitro experiments and clinical applications. As the field continues to evolve, this work underscores the translational potential of manipulating the microbiome to optimize neurological outcomes. It enriches our understanding of the intricate evolutionary interplay between host genomes and the microbial world.}, }
@article {pmid40414573, year = {2025}, author = {Yu, F and Ji, JL and Wang, Y and Liu, YD and Lian, YM and Wang, MZ and Cai, ZX}, title = {Anti-epileptic and Gut-protective Effects of Trioctanoin and the Critical Role of Gut Microbiota in a Mouse Model of Epilepsy.}, journal = {Brain research bulletin}, volume = {}, number = {}, pages = {111401}, doi = {10.1016/j.brainresbull.2025.111401}, pmid = {40414573}, issn = {1873-2747}, abstract = {Gut microbiota structure and function affect metabolism, gut health, and behavioral responses and are regulated by dietary factors. Recent research suggests the association of the gut-brain axis with epilepsy pathogenesis, thus offering potential new therapeutic targets. This study evaluated the anti-epileptic effect of trioctanoin and explored the potential role of the gut microbiota in a chronic pentylentetrazol (PTZ)-induced seizure mouse model. Behavioral assessments, electroencephalogram monitoring, immunofluorescence staining, neurotransmitter detection, gut microbiota sequencing, intestinal barrier function tests, and Fecal Microbiota Transplantation (FMT) were performed to systematically study the anti-epileptic effects of trioctanoin and the potential role of microbiota. Trioctanoin significantly restored glial cell proliferation to normal levels in chronic PTZ mice. Moreover, trioctanoin reduced elevated glutamate levels in the hippocampus of PTZ mice and improved gut microbiota imbalance and gut health by restoring the abundance of Dubosiella and Faecalibaculum genera, upregulating tight junction protein expression in the colon, and decreasing elevated levels of the inflammatory markers. Antibiotics(Abx) pre-treatment abolished the anticonvulsant protective effect of Trioctanoin. Although the FMT experiment did not transfer the anticonvulsant protection to the Abx+PTZ group mice, the results suggest that FMT still partially restored the gut microbiota imbalance in the chronic PTZ-induced epilepsy mouse model. These results provide new insights into dietary and gut microbiota-based therapeutic strategies for epilepsy.}, }
@article {pmid40413728, year = {2025}, author = {Kousgaard, SJ and Dall, SM and Albertsen, M and Nielsen, HL and Thorlacius-Ussing, O}, title = {Fecal microbiota transplantation from a healthy pouch donor for chronic pouchitis: a proof-of-concept study.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2510464}, doi = {10.1080/19490976.2025.2510464}, pmid = {40413728}, issn = {1949-0984}, mesh = {Humans ; *Pouchitis/therapy/microbiology ; *Fecal Microbiota Transplantation/adverse effects/methods ; Male ; Female ; Adult ; Middle Aged ; Feces/microbiology ; Quality of Life ; Chronic Disease/therapy ; Gastrointestinal Microbiome ; Proof of Concept Study ; Treatment Outcome ; Tissue Donors ; Denmark ; }, abstract = {Chronic pouchitis is a common complication after ileal pouch-anal anastomosis (IPAA) with limited treatment options. In this case series, we aimed to investigate clinical and microbiome changes, as well as adverse events, associated with using fecal microbiota transplantation (FMT) from a donor with a normal functioning IPAA to induce remission in patients with chronic pouchitis. Methods The study was a case-series including a 4-week intervention period and 12-month follow-up. Patients with chronic pouchitis who met the inclusion criteria were recruited from the Department of Gastrointestinal Surgery at Aalborg University Hospital, Denmark. Participants received FMT derived from a donor with a normal functioning IPAA. Treatment was administered by enema daily for two weeks, then every other day for two more weeks. Disease severity and quality of life (QoL) were accessed at baseline and 30-day follow-up. Clinical remission was defined as Pouchitis Disease Activity Index (PDAI) <7. Fecal samples from participants, healthy donors, and the IPAA donor were analyzed using shotgun metagenomic sequencing. Results Three patients with chronic pouchitis were included and completed the treatment protocol and follow-up visits. At the 30-day follow-up, all participants achieved clinical remission with reduced endoscopic inflammation. The median total PDAI score decreased from 8 (range 10-8) at baseline to 6 (range 6-5) at 30 days. Two participants reported improved QoL, while one reported no change. Few mild, self-limited adverse events were reported by all participants during treatment, with no serious events. Principal component analysis of fecal samples distinguished two clusters: healthy donors and the IPAA donor, with participant samples forming a separate cluster Conclusion We observed that all participants achieved clinical remission with reduced endoscopic inflammation following a 4-week FMT intervention. Adverse events were mild and self-limited. Metagenomic analysis revealed distinct microbiome clusters between IPAA donor and recipients, both of which differed from those of healthy donors.}, }
@article {pmid40413726, year = {2025}, author = {Zhang, DY and Li, D and Chen, SJ and Zhang, LJ and Zhu, XL and Chen, FD and Chen, C and Wang, Q and Du, Y and Xiong, JX and Huang, SM and Zhang, XD and Lv, YT and Zeng, F and Chen, RX and Huang, X and Mao, F and Zhou, S and Yao, Q and Huang, Y and Chen, R and Mo, Y and Xie, Y and Jiang, YH and Chen, Z and Mo, CY and Chen, JJ and Bai, FH}, title = {Bacteroides uniformis-generated hexadecanedioic acid ameliorates metabolic-associated fatty liver disease.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2508433}, doi = {10.1080/19490976.2025.2508433}, pmid = {40413726}, issn = {1949-0984}, mesh = {Humans ; Gastrointestinal Microbiome ; Animals ; *Bacteroides/metabolism/genetics ; Mice ; Male ; Female ; Middle Aged ; Feces/microbiology ; Liver/metabolism ; *Fatty Liver/microbiology/metabolism ; Fecal Microbiota Transplantation ; Prospective Studies ; Adult ; Metabolomics ; Mice, Inbred C57BL ; }, abstract = {Gut microbiota exerts a pivotal influence on the development of Metabolic Associated Fatty Liver Disease (MAFLD), although the specific contributions of individual bacterial strains and their metabolites remain poorly defined. We conducted stool shotgun metagenomic sequencing and plasma untargeted metabolomics in a large prospective cohort comprising 120 MAFLD patients and 120 matched healthy controls. The mechanisms and microbial-derived metabolites involved in MAFLD were further investigated through multi-omics analyses in vitro and in vivo. Distinct differences were identified in both the microbial community structure and metabolomic profiles between MAFLD patients and healthy controls. Bacteroides uniformis (B. uniformis) was the most significantly depleted species in MAFLD and negatively correlated with hepatic steatosis and BMI. MAFLD was characterized by marked disruptions in fatty acid and amino acid metabolism. Combined analysis of metabolomic and metagenomic data achieved high diagnostic accuracy for MAFLD and hepatic steatosis severity (AUC = 0.93). Transplantation of fecal microbiota from MAFLD subjects into ABX mice led to the onset of MAFLD-like symptoms, whereas B. uniformis administration alleviate disease progression by inhibiting intestinal fat absorption, FFA from eWAT influx into liver via the gut-liver axis, and IRE1α-XBP1s-mediated flipogenesis and ferroptosis, as confirmed by hepatic transcriptomic and proteomic analyses. Hexadecanedioic acid (HDA), potentially identified as a key metabolite produced by B. uniformis, ameliorated MAFLD symptoms. Mechanistically, B. uniformis-derived HDA also inhibited fat absorption and transported, and entered the liver via the portal vein to suppress IRE1α-XBP1s-mediated flipogenesis and ferroptosis. B. uniformis and its potential putative metabolite HDA may contribute to MAFLD progression modulation, through regulation of the IRE1α-XBP1s axis. This study provides new insights into the gut-liver axis in MAFLD and offers promising therapeutic targets based on specific microbes and their metabolites.}, }
@article {pmid40412060, year = {2025}, author = {Lin, Z and Wang, J and Luo, H and Huang, L and Pan, Z and Yang, S and Zhong, C and Shan, NC and Ye, Z and Tan, H and Yang, X and Zhang, B and Huang, C and Zhang, H}, title = {Changdiqing decoction (CDQD) ameliorates colitis via suppressing inflammatory macrophage activation and modulating gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {143}, number = {}, pages = {156856}, doi = {10.1016/j.phymed.2025.156856}, pmid = {40412060}, issn = {1618-095X}, abstract = {BACKGROUND: Ulcerative colitis (UC) is a non-specific inflammatory bowel disease. Unlike any single form of cell death reported previously, macrophage PANoptosis, a unique programmed cell death characterized by inflammation and necrosis, plays a crucial role in the pathogenesis of colitis. Changdiqing Decoction (CDQD), an empirical hospital prescription enema, has been used to treat UC for decades. This study aimed to investigate the multi-target anti-colitic effects of CDQD by examining its impact on intestinal homeostasis and its anti-inflammatory properties.<br><br>METHODS: A dextran sulfate sodium (DSS)-induced mouse model of acute colitis was employed. Interferon-gamma (IFN-&#x3b3;) and KPT-330 were used to induce macrophage PANoptosis. Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLCHRMS) was utilized to identify the chemical constituents of CDQD. Multi-omics analysis and fecal microbiota transplantation (FMT) were used to explore the therapeutic targets and gut microbiota alterations induced by CDQD.<br><br>RESULTS: CDQD treatment significantly alleviated colitis symptoms in mice, with a dose-dependent therapeutic effect. The decoction mitigated PANoptosis in colon tissues and bone marrow-derived macrophages (BMDMs). 16S rRNA sequencing analysis and metabonomics revealed that CDQD administration significantly altered the gut microbiota composition and metabolite profiles. Notably, CDQD-modulated gut microbiota exhibited anti-colitic effects through FMT. Integrated transcriptomics and network pharmacology analysis revealed that CDQD significantly downregulated the PI3K/Akt signaling pathway in colitis. This finding was further validated using the inhibitors LY294002 and MK2206.<br><br>CONCLUSIONS: CDQD alleviates colitis by suppressing inflammatory macrophage activation and modulating the gut microbiota. Our research provides a novel traditional Chinese medicine strategy for the treatment of UC via enema administration.}, }
@article {pmid40411710, year = {2025}, author = {Chen, L and Chen, C and Bai, Y and Li, C and Wei, C and Wei, R and Luo, R and Li, R and Ma, Q and Geng, Y}, title = {Evaluation of the effects of different formulations of protectants on the preservation of the microbiota in fecal microbiota transplantation.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {}, number = {}, pages = {}, pmid = {40411710}, issn = {1618-1905}, abstract = {BACKGROUND: With the increasing indications for fecal microbiota transplantation for the treatment of diseases, there is a growing demand for the preparation of frozen or lyophilized fecal microbiota products that are viable and can stably colonize the recipient. The addition of protective agents plays an important role in the preparation. However, there has been no systematic evaluation of the protective agents used in fecal microbiota sample transplantation preparation for transplantation.<br><br>METHODS: We were used the donor bacterial flora containing 10 different formulations of protective agents were frozen, lyophilized, and stored. Plate counting, CCK8 assay, flow cytometry after LIVE/DEAD staining, and fluorescence intensity were used to assess viable bacteria in vitro. In addition, the donor bacterial flora samples containing different formulations protective agents were transplanted into antibiotic-treated SPF mice, with 3 mice in each group and a total of 5 groups. Fecal samples were collected for metagenomic sequencing to observe the colonization of the bacterial flora in the recipient mice.<br><br>RESULTS: The preliminary screening results showed that the survival rate of bacteria in the 5% trehalose (T) groups, and 5% sucrose, 5% inulin, and 1% cysteine hydrochloride (SI) groups was slightly higher than that in the other groups. SI groups tended to be more protective against anaerobes than T groups. The donor gut microbiota containing the SI groups protective agent exhibited the best colonization of the recipient mice. The protective effects of different formulations of protective agents on the colonized probiotic strains and the metabolic function of the bacterial flora in recipient mice were found to be species specific.<br><br>CONCLUSIONS: SI groups can not only better protect the activity of anaerobic bacteria in the intestine, but also effectively promote the effective colonization of donor intestinal bacteria in the recipient mice, and the effect of frozen storage method is less, and can be used at the same time as frozen and freeze-dried preparation. It can be used as a reference for the selection of protective agents in the preparation of fecal microbiota transplantation samples.}, }
@article {pmid39581509, year = {2025}, author = {Chen, S and Wen, Q and Zhang, F}, title = {An Unusual Cause of Diarrhea and Hematochezia.}, journal = {Gastroenterology}, volume = {168}, number = {6}, pages = {1066-1070}, doi = {10.1053/j.gastro.2024.11.007}, pmid = {39581509}, issn = {1528-0012}, }
@article {pmid40411629, year = {2025}, author = {Nezhadi, J and Lahouty, M and Rezaee, MA and Fadaee, M}, title = {Clostridium difficile as a potent trigger of colorectal carcinogenesis.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {910}, pmid = {40411629}, issn = {2730-6011}, abstract = {Clostridium difficile, traditionally recognized as a cause of antibiotic-associated colitis, has emerged as a potential oncogenic factor in colorectal cancer (CRC). This article explores the mechanisms by which C. difficile toxins, TcdA and TcdB, contribute to CRC pathogenesis through epithelial barrier disruption, DNA damage, and chronic inflammation via NF-κB and STAT3 activation. Dysbiosis further exacerbates tumorigenesis by altering microbial metabolites. Understanding these interactions highlights potential therapeutic strategies, including toxin-neutralizing antibodies, fecal microbiota transplantation, and anti-inflammatory interventions, to mitigate CRC risk associated with C. difficile.}, }
@article {pmid40410854, year = {2025}, author = {Fan, L and Chen, J and Zhang, Q and Ren, J and Chen, Y and Yang, J and Wang, L and Guo, Z and Bu, P and Zhu, B and Zhao, Y and Wang, Y and Liu, X and Wang, W and Chen, Z and Gao, Q and Zheng, L and Cai, J}, title = {Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {133}, pmid = {40410854}, issn = {2049-2618}, support = {82300564//National Natural Science Foundation of China/ ; 81630014//National Natural Science Foundation of China/ ; BRWEP2024W012060100//Beijing Research Ward Excellence Program/ ; BRWEP2024W012060100//Beijing Research Ward Excellence Program/ ; 2024ZD0526804//National Science and Technology Major Project for the Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases and Metabolic Diseases/ ; 2024ZD0526800//National Science and Technology Major Project for the Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases and Metabolic Diseases/ ; BRWEP2024W012060105//Beijing Research Ward Excellence Program&#xff0c;BRWEP/ ; CIFMS, 2021-I2M-1-007//CAMS Innovation Fund for Medical Sciences/ ; 81825002//National Outstanding Youth Science Fund Project of National Natural Science Foundation of China/ ; BJJWZYJH01201910023029//Beijing Outstanding Young Scientist Program/ ; Z231100004623009//Beijing Municipal Science &amp; Technology Commission/ ; CI2021A00920//Key project of Science and Technology Innovation Project of China Academy of Chinese Medical Sciences/ ; ZLRK202511//Beijing Hospitals Authority Clinical medicine Development of special funding support/ ; L248105//Beijing Natural Science Foundation/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; Male ; Female ; *Hypertension/therapy/microbiology ; Adult ; *Gastrointestinal Microbiome/physiology ; Middle Aged ; Feces/microbiology ; Blood Pressure ; China ; Treatment Outcome ; }, abstract = {BACKGROUND: On the basis of the contribution of the gut microbiota to hypertension development, a novel strategy involving fecal microbiota transplantation (FMT) has been proposed to treat hypertension, but its efficacy has not been investigated in the clinic.<br><br>METHODS: In a randomized, blinded, placebo-controlled clinical trial (2021/03-2021/12, ClinicalTrials.gov, NCT04406129), hypertensive patients were recruited from seven centers in China, and received FMT or placebo capsules orally at three visits. The patients were randomized at a 1:1 ratio in blocks of four and stratified by center by an independent statistician. The intention-to-treat principle was implemented, as all randomized participants who received at least one intervention were included. The primary outcome was the decrease in office systolic blood pressure (SBP) from baseline to the day 30 visit. Adverse events (AEs) were recorded through the 3-month follow-up to assess safety measures. Alterations in BP, the fecal microbiome, and the plasma metabolome were assessed via exploratory analyses.<br><br>RESULTS: This study included 124 patients (mean age 43&#xa0;years, 73.4% men) who received FMT (n&#x2009;=&#x2009;63) or placebo (n&#x2009;=&#x2009;61) capsules. The numbers of participants who experienced AEs (13 (20.6%) vs. 9 (14.8%), p&#x2009;=&#x2009;0.39) and the primary outcome (6.28 (11.83) vs. 5.77 (10.06) mmHg, p&#x2009;=&#x2009;0.62) were comparable between the groups. The FMT group presented a decrease in SBP after 1&#xa0;week of FMT, with a between-arm difference of&#x2009;-&#x2009;4.34 (95% CI,&#x2009;-&#x2009;8.1 to&#x2009;-&#x2009;0.58; p&#x2009;=&#x2009;0.024) mmHg, but this difference did not persist even after repeated intervention. After FMT, shifts in microbial richness and structure were identified and the abundance of the phyla Firmicutes and Bacteroidetes was altered. Decreases in the abundances of Eggerthella lenta, Erysipelatoclostridium ramosum, Anaerostipes hadrus, Gemella haemolysans, and Streptococcus vestibularis and increases in the abundances of Parabacteroides merdae, Prevotella copri, Bacteroides galacturonicus, Eubacterium sp. CAG 180, Desulfovibrio piger, Megamonas hypermegale, Collinsella stercoris, Coprococcus catus, and Allisonella histaminiformans were identified and correlated with office SBP. Those species were also correlated with responding and inversely office SBP-associated metabolites including tyrosine, glutamine, aspartate, phenylalanine, methionine, serine, sarcosine, and/or asparagine.<br><br>CONCLUSIONS: Safety but unsustainable BP reduction was observed in the first trial of the effects of FMT on hypertension. Additional intervention studies on specific microbes with metabolite-targeting and BP-modulating features are needed. Video Abstract.}, }
@article {pmid40409520, year = {2025}, author = {Sen, U}, title = {Gut microbiota and well-being: a comprehensive summary of the special issue.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107791}, doi = {10.1016/j.phrs.2025.107791}, pmid = {40409520}, issn = {1096-1186}, abstract = {Gut microbes play an immense role in digesting ingested food, providing nutrients to the host, and producing several bioactive metabolites that not only help maintain health but can also elicit disease during dysbiotic conditions. The bioactive compounds derived from gut microbiota metabolites include trimethylamine-N-oxide (TMAO), uremic toxins, short chain fatty acids (SCFAs), phytoestrogens, anthocyanins, bile acids, lipopolysaccharide - to name a few. Once these compounds enter the host cells, tissues, and organs they can cause diseases such as epigenetic, metabolic, neurodegenerative, psychiatric, cardiovascular, hypertension, respiratory, gastrointestinal, kidney, bone, cancer, and others. Regulating healthy gut microbiota thus provides a potential option for the prevention, reversal, or even treatment of these diseases. Towards this end, various interventional strategies are postulated in this field of emerged and rapidly expanding health research arena that includes fecal microbiota transplantation, prebiotics, and probiotics, and to introduce the concept that correcting gut dysbiosis can ameliorate disease symptoms, thus offering a new approach towards dysbiosis-related disease mitigation and treatment. In the special issue of Pharmacological Research titled "Gut Microbiota and Well-Being," several outstanding research findings and review articles are published, covering a broad spectrum of topics related to the influence of gut microbiota on health and disease. This editorial summarizes each of these contributions, prioritizing research findings before discussing the review articles. The summaries are restructured abstracts of relevant articles focusing on major findings or thematic topics.}, }
@article {pmid40409481, year = {2025}, author = {Chen, E and Zhou, W}, title = {Immunotherapy in Microsatellite-Stable Colorectal Cancer: Strategies to Overcome Resistance.}, journal = {Critical reviews in oncology/hematology}, volume = {}, number = {}, pages = {104775}, doi = {10.1016/j.critrevonc.2025.104775}, pmid = {40409481}, issn = {1879-0461}, abstract = {Colorectal cancer (CRC) is among the foremost causes of cancer-related mortality worldwide; however, individuals with microsatellite-stable (MSS) disease-who constitute most CRC diagnoses-derive limited benefit from existing immunotherapeutic approaches. Here, we outline emerging methods designed to address the inherent resistance of MSS CRC to immune checkpoint inhibitors (ICIs). Recent findings emphasize how the immunosuppressive tumor microenvironment (TME) in MSS CRC, marked by diminished immunogenicity and high levels of regulatory T cells and myeloid-derived suppressor cells, restricts effective antitumor immune activity. Combination regimens that merge ICIs with chemotherapy, anti-angiogenic agents, or targeted blockade of pathways such as TGF-β and VEGF have shown encouraging early outcomes, including enhanced antigen presentation and T-cell penetration. Novel immunomodulatory platforms-such as epigenetic modifiers, oncolytic viruses, and engineered probiotic vaccines-are under assessment to further reprogram the TME and boost therapeutic efficacy. Concurrently, progress in adoptive cell therapies (for example, chimeric antigen receptor (CAR) T cells) and the development of cancer vaccines targeting tumor-associated and neoantigens promise to extend immune control over MSS CRC. In parallel, improving patient selection through predictive biomarkers-from circulating tumor DNA (ctDNA) to gene expression signatures and specific molecular subtypes-could refine individualized treatment strategies. Finally, interventions that alter the gut microbiome, including probiotics and fecal transplantation, serve as complementary tools to strengthen ICI responses. Taken together, these insights and combined treatment strategies lay the foundation for more successful immunotherapeutic interventions in MSS CRC, ultimately aiming to provide sustained clinical benefits to a broader spectrum of patients.}, }
@article {pmid40406094, year = {2025}, author = {Eslami, M and Naderian, R and Bahar, A and Babaeizad, A and Rezanavaz Gheshlagh, S and Oksenych, V and Tahmasebi, H}, title = {Microbiota as diagnostic biomarkers: advancing early cancer detection and personalized therapeutic approaches through microbiome profiling.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1559480}, pmid = {40406094}, issn = {1664-3224}, mesh = {Humans ; Precision Medicine/methods ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/diagnosis/therapy/microbiology ; *Early Detection of Cancer/methods ; *Biomarkers, Tumor ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {The important function of microbiota as therapeutic modulators and diagnostic biomarkers in cancer has been shown by recent developments in microbiome research. The intricate interplay between the gut microbiota and the development of cancer, especially in colorectal and breast cancers, emphasizes how microbial profiling may be used for precision treatment and early diagnosis. Important microbial signatures, including Bacteroides fragilis and Fusobacterium nucleatum, have been linked to the development and progression of cancer, providing important information on the processes behind carcinogenesis. Additionally, the influence of microbiota on the effectiveness of treatments such as immunotherapy and chemotherapy highlights its dual function in improving treatment outcomes and reducing side effects. To optimize treatment results, strategies including dietary changes and fecal microbiota transplantation (FMT) are being investigated. Despite these developments, there are still issues, such as individual variations in microbial composition, a lack of standardized procedures, and the requirement for reliable biomarkers. Integrating microbiome-based diagnostics with conventional approaches, such as liquid biopsies and machine learning algorithms, could revolutionize cancer detection and management. This review provides an overview of the current understanding of the host-microbe immunological axis and discusses emerging therapeutic strategies centered on microbiota modulation to support human health. Further research is essential to overcome existing challenges and fully realize the promise of microbiota-driven innovations in oncology.}, }
@article {pmid40402463, year = {2025}, author = {Li, L and Hu, M and Zhu, X and Huang, X and Chen, H}, title = {Microbiota Transplantation in Tumor Immunology Studies.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2930}, number = {}, pages = {295-306}, pmid = {40402463}, issn = {1940-6029}, mesh = {*Neoplasms/immunology/therapy/microbiology/pathology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; Animals ; Humans ; Mice ; Feces/microbiology ; }, abstract = {This protocol outlines the standardized procedures for utilizing fecal microbiota transplantation (FMT) in tumor immunology studies. FMT, the process of transferring gut microbiota from a healthy donor to a recipient, has shown potential in modulating the immune response against tumors. This protocol details the selection criteria for donors and recipients, preparation and processing of fecal material, and the administration routes for transplantation. Additionally, it describes the pre- and posttransplantation monitoring of microbiota composition, immune parameters, and tumor progression. By following this protocol, researchers can systematically investigate the impact of microbiota on tumor growth and immune modulation, contributing to the development of microbiota-based therapeutic strategies in oncology.}, }
@article {pmid40401951, year = {2025}, author = {Huang, J and Qiao, H and Li, Q and Zhang, Y and Zhang, C and Su, H and Sun, X}, title = {Osteopontin protects from ovalbumin-induced asthma by preserving the microbiome and the intestinal barrier function.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0038925}, doi = {10.1128/msystems.00389-25}, pmid = {40401951}, issn = {2379-5077}, abstract = {UNLABELLED: The gut and lung microbiota are associated with asthma. Osteopontin (OPN) is an important cytokine associated with several inflammatory diseases. The potential role of OPN in the asthma-associated microbiome remains poorly understood. Here, we investigated whether OPN could moderate asthma by affecting the gut and lung microbiota. Our results showed that compared with wild-type (WT) mice, Spp1[-/-] mice exhibited immune cell infiltration in the lung, OVA-specific IgG1, increased levels of Th2- and Th17-related inflammatory factors, and decreased levels of Th1-related inflammatory factors and forkhead box P3 (FOXP3) expression, resulting in a Th1/Th2 and Th17/Treg imbalance. In addition, gut structure was impaired, and expression of tight junction-related proteins was reduced in Spp1[-/-] mice, which disrupted gut barrier function. Importantly, OPN-deficient significantly aggravated gut and lung microbiota dysbiosis in OVA-induced asthmatic mice. The results of high-throughput 16S rRNA sequencing demonstrated that OPN-deficient mice showed a substantial reduction in beneficial gut and lung bacteria (Bacteroidetes, Lactobacillus, Allobaculum), and an OVA-induced increase in the abundance of bacteria associated with potentially pathogenic gut and lung (Epsilonbacteraeota, Helicobacter, Desulfovibrio, Oscillibacter)-associated bacteria was elevated in abundance. Allobaculum was negatively correlated with interleukin-4 and GATA-3 and was positively correlated with interferon gamma and FOXP3. Moreover, through fecal microbiota transplantation, we found that OVA-induced IgE and IgG1 levels were reduced in OPN-deficient asthmatic mice, Th1/Th2 and Th17/Treg balance was maintained, gut barrier function was improved, and microbiome changes in OPN-deficient mice were compensated for, with an elevated abundance of Allobaculum and reduced abundance of Desulfovibrio and Oscillibacter. We further discovered that OPN deficiency reduces FOXP3 expression and decreases Lactobacillus colonization through activation of the PD-1/PD-L1 pathway in the intestine and lung. The present study suggests that OPN may moderate OVA-induced asthma by modulating the gut and lung microbiota.<br><br>IMPORTANCE: Osteopontin deficiency exacerbated asthmatic airway inflammation, an effect associated with microbiota dysbiosis, impaired intestinal barrier function, and increased PD-1/PD-L1 expression and thus decreased Treg cell function. The study provides clinicians with new insights into asthma mechanisms and can also lead to new ideas for asthma treatment.}, }
@article {pmid40401932, year = {2025}, author = {McMullen, BN and Chen See, J and Baker, S and Wright, JR and Anderson, SLC and Yochum, G and Koltun, W and Portolese, A and Jeganathan, NA and Lamendella, R}, title = {Metatranscriptomic analysis of colonic mucosal samples exploring the functional role of active microbial consortia in complicated diverticulitis.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0243124}, doi = {10.1128/spectrum.02431-24}, pmid = {40401932}, issn = {2165-0497}, abstract = {In this study, we investigated complicated diverticulitis, an inflammatory condition associated with abscesses, fistulas, intestinal obstructions, perforations, and primarily affects adults over the age of 60. Although the exact etiology remains unclear, the gut microbiome has been suggested as a contributing factor. Previous studies have used 16S rRNA gene analysis from patient fecal samples, which is limited to identifying the bacterial communities present. Herein, we employed shotgun metatranscriptomics on 40 patient-matched samples of diseased and adjacent normal colonic mucosal tissues from 20 patients with complicated diverticulitis to gain a more comprehensive understanding of active microbial taxa and gene expression patterns that may be involved in this disease state. Our findings revealed distinct beta diversity and a conglomerate of pathogenic microbiota in the diseased tissues, including Staphylococcus cohnii, Corynebacterium jeikeium, Kineococcus, Talaromyces rugulosus, Campylobacteraceae, and Ottowia, among others. The adjacent normal tissues were a stark contrast, harboring anti-inflammatory taxa such as Streptococcus salivarius and housekeeping genes and pathways such as the ABC-2 type transport system ATP-binding protein. These results align with previous amplicon sequencing studies and provide novel functional insights that may be crucial for understanding the etiology of complicated diverticulitis.IMPORTANCEComplicated diverticulitis is a virulent condition with no clear cause other than the association with colonic diverticulosis. We assessed the microbial gene expression in complicated diverticulitis patients using colonic tissue samples, revealing microbes in the diseased tissue known to exacerbate the diverticular condition and to live in extreme places, and microbes in patients' normal tissue known to maintain normal bodily functions. This functional information is therefore important for understanding what microbial taxa are present and what they are doing. It is possible clinicians could someday harness this information to more effectively treat complicated diverticulitis symptoms. For example, clinicians may suggest dietary changes and prescribe probiotics to increase beneficial bacteria. Clinicians may also prescribe targeted antibiotics or consider the emerging treatment option of fecal transplants in complicated diverticulitis patients. While not curing complicated diverticulitis, each potential treatment option mentioned addresses balancing out dysbiosis of the gut microbiome, therefore alleviating associated symptoms.}, }
@article {pmid40400677, year = {2025}, author = {Men, J and Cui, C and Li, H and Li, Z and Zhang, Y and Liu, Z and Wang, Q and Liu, P and Zou, S and Yu, Z and Zhang, Y and Wu, S and Zhu, G and Wang, P and Huang, X}, title = {Cold water swimming reshapes gut microbiome to improve high-fat diet-induced obesity.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1589902}, pmid = {40400677}, issn = {1664-302X}, abstract = {Hypothermia and swimming have been shown to alleviate high-fat diet (HFD)-induced obesity, with effects linked to the gut microbiota (GM). However, whether the effects of cold water swimming (CWS) on GM can be effectively transferred through fecal microbiota transplantation (FMT) has not been investigated. This study established mice models of obesity, CWS and FMT to investigate the mechanism by which CWS reshapes GM to improve HFD-induced obesity. Additionally, we analyzed the relationship between obesity phenotypes, GM composition, gene expression and CWS. The study found that HFD induced obesity phenotypes and GM dysbiosis in mice, while CWS produced opposite effects. The FMT results confirmed that CWS effectively alleviated HFD-induced lipid accumulation, metabolic disorders, and chronic inflammatory responses, which are associated with increased GM diversity, enrichment of beneficial bacteria, and the repair of intestinal barrier damage. Furthermore, these beneficial effects can be effectively transferred via FMT. The evidence from this study suggests that GM plays a critical role in the anti-obesity effects of CWS, with intestinal barrier repair emerging as a potential therapeutic target. This also provides scientific evidence for the feasibility of FMT as a strategy to combat obesity.}, }
@article {pmid40399878, year = {2025}, author = {Qian, S and Su, Z and Lin, J and Hou, Q and Wang, X and Li, Y and Wang, J and Huang, C and Wang, Z and Cubero, FJ and Wang, X and Liao, L}, title = {Inhibition of Farnesoid-x-receptor signaling during abdominal sepsis by dysbiosis exacerbates gut barrier dysfunction.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {236}, pmid = {40399878}, issn = {1478-811X}, support = {81971814//the National Natural Science Foundation of China/ ; 81971814//the National Natural Science Foundation of China/ ; 81971814//the National Natural Science Foundation of China/ ; 81971814//the National Natural Science Foundation of China/ ; 20192BAB205013//the Natural Science Foundation of Jiangxi Province/ ; 20192BAB205013//the Natural Science Foundation of Jiangxi Province/ ; 20192BAB205013//the Natural Science Foundation of Jiangxi Province/ ; PWRd2020-06//Academic medicine leader's training Program in health systems of Pudong New Area/ ; PWYgf2021-03//Shanghai Pudong New Area Summit (emergency medicine and critical care) construction project/ ; 23Y11908300//Medical Innovation Research Special Project of Shanghai 2023 Science and Technology Innovation Action Plan/ ; 2020PJD050//Shanghai Pujiang Program/ ; }, mesh = {Animals ; *Receptors, Cytoplasmic and Nuclear/metabolism/agonists ; *Sepsis/metabolism/pathology/microbiology ; *Signal Transduction ; *Dysbiosis/metabolism/pathology ; Mice ; Myeloid Differentiation Factor 88/metabolism ; Fibroblast Growth Factors/metabolism ; Mice, Inbred C57BL ; Gastrointestinal Microbiome ; Male ; *Intestinal Mucosa/metabolism ; Liver/metabolism ; Bile Acids and Salts/metabolism ; }, abstract = {BACKGROUND AND AIMS: Bacterial translocation and intestinal dysbiosis due to gut barrier dysfunction are widely recognized as major causes of the initiation and development of intra-abdominal sepsis. Systemic bacterial translocation and hepatic activation of the myeloid differentiation primary response gene 88 (Myd88) can disturb bile acids (BAs) metabolism, further exacerbating intestinal dysbiosis. The farnesoid X receptor (FXR) and fibroblast growth factor (FGF) 15/19 are well known to be involved in the control of BAs synthesis and enterohepatic circulation. However, the influence of intestinal microbiota on intestinal Myd88 signaling, the FXR/FGF15 axis, as well as gut-liver crosstalk during sepsis remains unclear. The present study aims to decipher the role of intestinal Myd88 in abdominal sepsis, its impact on intestinal FXR signaling and FGF15-mediated gut-liver crosstalk.<br><br>METHODS: Expression levels of FXR and FGF15 in the liver and intestines, alongside assessments of gut barrier function, were evaluated in septic wild-type (WT) mice 24&#xa0;h post-cecal ligation and puncture (CLP) surgery. Subsequently, the FXR agonist INT-747 was administered to explore the relationship between FXR activation and gut barrier function. Further investigations involved Myd88-deficient mice with specific deletion of Myd88 in intestinal epithelial cells (Myd88[&#x25b3;IEC]), subjected to CLP to examine the interplay among intestinal Myd88, FXR, gut barrier function, microbiota, and BA composition. Additionally, fecal microbiota transplantation (FMT) from septic mice to Myd88[&#x25b3;IEC] mice was conducted to study the impact of dysbiosis on intestinal Myd88 expression during sepsis, using floxed (Myd88[fl/fl]) mice as controls. Finally, the effects of the probiotic intervention on gut barrier function and sepsis outcomes in CLP mice were investigated.<br><br>RESULTS: Induction of sepsis via CLP led to hepatic cholestasis, suppressed FXR-FGF15 signaling, altered gut microbiota composition, and compromised gut barrier function. Administration of INT-747 increased intestinal FXR and FGF15 expression, strengthened gut barrier function, and enhanced barrier integrity. Interestingly, Myd88[&#x25b3;IEC] mice exhibited partial reversal of sepsis-induced changes in FXR signaling, BA metabolism, and intestinal function, suggesting enhanced FXR expression upon Myd88 knockdown. Moreover, FMT from septic mice activated intestinal Myd88, subsequently suppressing FXR-FGF15 signaling, exacerbating cholestasis, and ultimately compromising gut barrier function. Probiotic treatment during abdominal sepsis mitigated flora disturbances, reduced Myd88 activation in the intestinal epithelium, increased FXR expression, alleviated cholestasis, and consequently reduced barrier damage.<br><br>CONCLUSIONS: This study highlights the critical role of Myd88/FXR signaling in intestinal epithelial cells as a pivotal mediator of the detrimental effects induced by sepsis-related intestinal dysbiosis on barrier function and bile acid metabolism. In summary, disordered intestinal flora in septic mice specifically triggers intestinal epithelial Myd88 activation, inhibit the FXR-FGF15 axis, and then worsen intestinal barrier function impairment.}, }
@article {pmid40339798, year = {2025}, author = {Gîlcă-Blanariu, GE and Pakpour, S and Kao, D}, title = {More questions than answers? Predicting faecal microbiota transplantation outcomes for recurrent Clostridioides difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2025.04.036}, pmid = {40339798}, issn = {1469-0691}, }
@article {pmid40398680, year = {2025}, author = {Zhou, Y and Komnick, MR and Sepulveda, F and Liu, G and Nieves-Ortiz, E and Meador, K and Ndatabaye, O and Fatkhullina, A and Bozicevich, A and Juengel, B and Wu-Woods, NJ and Naydenkov, PM and Kent, J and Christiansen, N and Madariaga, ML and Witkowski, P and Ismagilov, RF and Esterházy, D}, title = {Inducible, but not constitutive, pancreatic REG/Reg isoforms are regulated by intestinal microbiota and pancreatic diseases.}, journal = {Mucosal immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.mucimm.2025.05.003}, pmid = {40398680}, issn = {1935-3456}, abstract = {The REG/Reg gene locus encodes a conserved family of potent antimicrobial but also pancreatitis-associated proteins. Here we investigated whether REG/Reg family members differ in their baseline expression levels and abilities to be regulated in the pancreas and gut upon perturbations. We found, in humans and mice, the pancreas and gut differed in REG/Reg isoform levels and preferences, with the duodenum most resembling the pancreas. Pancreatic acinar cells and intestinal enterocytes were the dominant REG producers. Intestinal symbiotic microbes regulated the expression of the same, select Reg members in gut and pancreas. These Reg members had the most STAT3-binding sites close to the transcription start sites and were partially IL-22 dependent. We thus categorized them as "inducible" and others as "constitutive". Indeed, in pancreatic ductal adenocarcinoma and pancreatitis models, only inducible Reg members were upregulated in the pancreas. While intestinal Reg expression remained unchanged upon pancreatic perturbation, pancreatitis altered the microbial composition of the duodenum and feces shortly after disease onset. Our study reveals differential usage and regulation of REG/Reg isoforms as a mechanism for tissue-specific innate immunity, highlights the intimate connection of pancreas and duodenum, and implies a gut-to-pancreas communication axis resulting in a coordinated Reg response.}, }
@article {pmid40398524, year = {2025}, author = {He, X and Wei, X and He, Z and Yao, C and Nie, M and Ma, X and Chen, Q and Guo, DA}, title = {Biotransformation of artemisinin by human intestinal fungi and cytotoxicity against breast cancer cells of its metabolites.}, journal = {Phytochemistry}, volume = {}, number = {}, pages = {114551}, doi = {10.1016/j.phytochem.2025.114551}, pmid = {40398524}, issn = {1873-3700}, abstract = {Artemisinin widely exists in the Artemisia annua L. and is the front-line of antimalarial drugs. In this study, microbial transformation of artemisinin was performed based on seventeen human intestinal fungal species. Our findings revealed that isomerization and deoxygenation were the most prevalent metabolic pathways in fungi. Incubation of artemisinin with Rhizopus microspores (PT2906) and Candida boidinii (M7017B) afforded three new compounds (P3, P5 and P6) along with seven known metabolites which were elucidated by extensive spectroscopic data analysis. All metabolites were evaluated for their cytotoxicity against MCF-7 cells, and the results showed that 3β-hydroxydeoxyartemisinin (P5) suppressed the growth of MCF-7 cells better than artemisinin. In addition, ten artemisinin isomers were found in the feces of antibiotic-treated mice after M7017B transplantation, demonstrating that human intestinal fungi have the potential to participate in the in vivo intestinal transformation of artemisinin.}, }
@article {pmid40398303, year = {2025}, author = {Xu, Y and Chen, K and Huang, Y and Yan, Y and Zhang, W and Tian, J and Zhang, D and Liu, M and Nie, Q}, title = {Fecal microbiota transplantation improves growth performance of chickens by increasing the intestinal Lactobacillus and glutamine.}, journal = {Poultry science}, volume = {104}, number = {8}, pages = {105243}, doi = {10.1016/j.psj.2025.105243}, pmid = {40398303}, issn = {1525-3171}, abstract = {Chicken meat is an essential source of high-quality animal protein, mainly derived from slow-growth chicken (SC) and fast-growth chicken (FC) breeds. Skeletal muscle is a highly adaptable tissue that is influenced by breed differences and the gut microbiome. Investigation whether remodeling the gut microbiota by fecal microbiota transplantation (FMT) improves chicken growth is an interesting question. We compared the gut microbial composition of eight breeds of SC (Xinghua chicken, Yangshan chicken, Zhongshan Salan chicken, Qingyuan Partridge chicken, Huiyang Bearded chicken and Huaixiang chicken) and FC (Xiaobai chicken and White rock chicken). Fecal microbiota from donor FC (Xiaobai chickens) with superior growth performance were transferred to SC (Xinghua chickens). The effects of FMT on growth performance, metabolic profile and gut microbiome of recipient chickens were evaluated. We found significant differences in gut microbial composition, with a higher abundance of Bacteroidetes in SC and a higher abundance of Firmicutes in FC. Xiaobai chickens with better growth performance and abundant Lactobacillus, and FMT significantly enhanced growth performance, the expression of mRNA (MYOG, MYF5, MYF6 and IGF1) related to breast and leg muscle development and improved the villus/crypt ratio in the jejunum. FMT altered the microbiota in the duodenum, jejunum, and ileum, increased Lactobacillus abundance, decreased the relative mRNA expression of the intestinal inflammatory factors (IL-1β, IL-6 and TNF-α), increased glutamine levels in the host, including in muscle tissues and intestinal contents, and Spearman correlation analysis indicated that the relative abundance of Lactobacillus was positively correlated with glutamine levels. Additionally, antibiotic treatment reduces glutamine levels in the intestines, blood, and muscle tissues of chickens. Glutamine can increase the expression of cyclinD1, cyclinD2, cyclinB2, MYOG, MYF5, MYF6 and IGF1 mRNA to promote chicken myoblasts proliferation and differentiation. This study found that the SC and FC gut microbes were significantly different, and the FC chicken gut microbes were able to reshape the FC gut microbiota through FMT, i.e., higher Lactobacillus, promoted chicken myoblasts proliferation and differentiation and growth performance by increasing glutamine levels.}, }
@article {pmid40395920, year = {2025}, author = {Ishikawa, D and Zhang, X and Nagahara, A}, title = {Current Applications and Future Prospects of Fecal Microbiota Transplantation.}, journal = {Juntendo medical journal}, volume = {71}, number = {2}, pages = {68-75}, pmid = {40395920}, issn = {2759-7504}, abstract = {In recent years, the impact of gut microbiota on human health has gained increasing recognition, highlighting the potential benefits of regulating gut microbiota for patient care. Consequently, fecal microbiota transplantation (FMT) has emerged as a novel treatment for improving dysbiosis. It is necessary to summarize and discuss the current research and future development possibilities. This advanced microbial therapy restores the gut microbiome by introducing a diverse array of microorganisms from healthy donors, thereby correcting dysbiosis and re-establishing a fully functional ecosystem. Ongoing research on FMT is actively conducted in various fields worldwide. This study provides an overview of the progress of clinical research on the effects of FMT in gastrointestinal diseases, immune checkpoint inhibitors, allergic diseases, and central nervous system diseases, as well as the results of our ongoing clinical study on "FMT combined with antibiotics for ulcerative colitis."}, }
@article {pmid40395507, year = {2025}, author = {Shabani, M and Ghoshehy, A and Mottaghi, AM and Chegini, Z and Kerami, A and Shariati, A and Taati Moghadam, M}, title = {The relationship between gut microbiome and human diseases: mechanisms, predisposing factors and potential intervention.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1516010}, pmid = {40395507}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Probiotics ; Prebiotics ; Metabolic Diseases/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/microbiology ; Nervous System Diseases/microbiology ; Disease Susceptibility ; Diet ; Diabetes Mellitus, Type 2/microbiology ; }, abstract = {The complex interrelation of gut microbiota with human health underlines the profound influence this microbial ecosystem has on mechanisms of disease and wellness. The gut microbiome profoundly impacts various human diseases, encompassing gastrointestinal disorders, metabolic disorders, neurological disorders, and immune-related diseases. Gastrointestinal disorders are closely linked to microbial imbalances in the gut. Metabolic disorders, including obesity and type 2 diabetes, are influenced by the gut microbiota's role in energy regulation and glucose metabolism. Furthermore, the gut-brain axis highlights the correlation between gut microbiota and neurological conditions such as Alzheimer's and Parkinson's. Moreover, the gut microbiome assumes a pivotal function in regulating the immune system, whereby dysbiosis is implicated in developing immunological-related ailments, including allergies and autoimmune disorders. Predisposing factors, including diet, medicines, lifestyle, and environmental influences, are described as having an important role in the composition of the gut microbiome. By understanding these factors, we can get valuable insights into how to intervene to reduce the chances of a disease. Current interventions, including probiotics, prebiotics, fecal microbiota transplants, and lifestyle modification, show promise, but there are still challenges and unanswered questions in this evolving field that may lead to improvements. This review interrelates the complicated gut microbiome with various human diseases, mechanisms, predisposing factors, and potential interventions.}, }
@article {pmid40394204, year = {2025}, author = {Oliver, PJ and Civitelli, L and Hu, MT}, title = {The gut-brain axis in early Parkinson's disease: from prodrome to prevention.}, journal = {Journal of neurology}, volume = {272}, number = {6}, pages = {413}, pmid = {40394204}, issn = {1432-1459}, mesh = {Humans ; *Parkinson Disease/prevention &amp; control/metabolism/microbiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; alpha-Synuclein/metabolism ; *Prodromal Symptoms ; *Brain-Gut Axis/physiology ; *Brain/metabolism ; Dysbiosis ; Animals ; }, abstract = {Parkinson's disease is the second most common neurodegenerative disorder and fastest growing neurological condition worldwide, yet its etiology and progression remain poorly understood. This disorder is characterized pathologically by the prion-like spread of misfolded neuronal alpha-synuclein proteins in specific brain regions leading to Lewy body formation, neurodegeneration, and progressive neurological impairment. It is unclear what triggers Parkinson's and where α-synuclein protein aggregation begins, although proposed induction sites include the olfactory bulb and dorsal motor nucleus of the vagus nerve. Within the last 20 years, there has been increasing evidence that Parkinson's could be triggered by early microbiome changes and α-synuclein accumulation in the gastrointestinal system. Gut microbiota dysbiosis that alters gastrointestinal motility, permeability, and inflammation could enable prion-like spread of α-synuclein from the gut-to-brain via the enteric nervous system. Individuals with isolated rapid eye movement sleep behavior disorder have a high likelihood of developing Parkinson's and might represent a prodromal 'gut-first' subtype of the condition. The gut-first model of Parkinson's offers novel gut-based therapeutic avenues, such as anti-, pre-, and pro-biotic preparations and fecal microbiota transplants. Crucially, gut-based interventions offer an avenue to treat Parkinson's at early prodromal stages with the aim of mitigating evolution to clinically recognizable Parkinson's disease characterized by motor impairment.}, }
@article {pmid40300608, year = {2025}, author = {Wirbel, J and Andermann, TM and Brooks, EF and Evans, L and Groth, A and Dvorak, M and Chakraborty, M and Palushaj, B and Reynolds, GZM and Porter, IE and Al Malki, M and Rezvani, A and Gooptu, M and Elmariah, H and Runaas, L and Fei, T and Martens, MJ and Bolaños-Meade, J and Hamadani, M and Holtan, S and Jenq, R and Peled, JU and Horowitz, MM and Poston, KL and Saber, W and Kean, LS and Perales, MA and Bhatt, AS}, title = {Accurate prediction of absolute prokaryotic abundance from DNA concentration.}, journal = {Cell reports methods}, volume = {5}, number = {5}, pages = {101030}, doi = {10.1016/j.crmeth.2025.101030}, pmid = {40300608}, issn = {2667-2375}, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; *DNA, Bacterial/genetics/analysis ; Machine Learning ; *Prokaryotic Cells ; Male ; Parkinson Disease/microbiology ; }, abstract = {Quantification of the absolute microbial abundance in a human stool sample is crucial for a comprehensive understanding of the microbial ecosystem, but this information is lost upon metagenomic sequencing. While several methods exist to measure absolute microbial abundance, they are technically challenging and costly, presenting an opportunity for machine learning. Here, we observe a strong correlation between DNA concentration and the absolute number of 16S ribosomal RNA copies as measured by digital droplet PCR in clinical stool samples from individuals undergoing hematopoietic cell transplantation (BMT CTN 1801). Based on this correlation and additional measurements, we trained an accurate yet simple machine learning model for the prediction of absolute prokaryotic load, which showed exceptional prediction accuracy on an external cohort that includes people living with Parkinson's disease and healthy controls. We propose that, with further validation, this model has the potential to enable accurate absolute abundance estimation based on readily available sample measurements.}, }
@article {pmid40393939, year = {2025}, author = {Zhang, X and He, Q and Zhang, C and Ji, Z and Yang, D and Wang, X and Liu, C and Zhang, C and Yuan, J and Xu, N and Chu, J}, title = {Gegen Qinlian Decoction protects kidney in diabetic rats by improving intestinal barrier and regulating intestinal microbiota.}, journal = {The Journal of pharmacy and pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jpp/rgaf030}, pmid = {40393939}, issn = {2042-7158}, support = {82204707//National Natural Science Foundation of China/ ; }, abstract = {OBJECTIVES: To investigate the renoprotective effects of Gegen Qinlian Decoction (GQD) in Diabetes mellitus (DM) rats via the intestinal barrier and microbiota.<br><br>METHODS: GQD was analyzed by UPLC. STZ-induced DM rat models and antibiotic-induced sterile DM rat models were established, and fecal microbiota transplantation was performed in the latter. Renal function, oxidative stress, serum inflammatory factors, and pathological alterations were assessed. Intestinal cells and tight junction were observed by transmission electron microscopy. Inflammatory factors in the colon and tight junction protein expression were evaluated. The gut microbiota and its abundance were assessed by 16sRNA sequencing.<br><br>KEY FINDINGS: Four components were determined in the GQD, including puerarin, baicalin, berberine, and liquiritin. After GQD treatment, Scr and BUN were reduced, renal pathological changes were attenuated, intestinal cell swelling was reduced, intestinal tight junctions were improved, and GQD modulated the intestinal microbiota. Furthermore, a fecal bacterial solution containing GQD reduced renal lesions, improved intestinal tight junctions, and regulated intestinal microbiota in DM rats.<br><br>CONCLUSIONS: GQD regulated the intestinal microbiota of DM rats, reduced intestinal inflammation, and repaired the intestinal barrier, thus reducing the burden on the kidneys, and exerting a protective effect on the kidneys of DM rats.}, }
@article {pmid40393246, year = {2025}, author = {Liu, X and Li, Y and Yuan, C and Zhao, Y and Zhou, L and Yan, Y and Ren, J and Liu, Q}, title = {Sophocarpine suppresses MAPK-mediated inflammation by restoring gut microbiota in colorectal cancer.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {143}, number = {}, pages = {156833}, doi = {10.1016/j.phymed.2025.156833}, pmid = {40393246}, issn = {1618-095X}, abstract = {BACKGROUND: Colorectal cancer (CRC), as one of the most common cancers globally, poses a significant challenge to public health due to its high incidence and mortality rates. This underscores the need for continuous exploration of new therapeutic targets and effective drugs. Sophocarpine (SC), a natural compound derived from traditional Chinese medicine, holds considerable therapeutic potential in the treatment of CRC, however, the relevant mechanisms remains unclear.<br><br>PURPOSE: This study aims to explore the anti-tumor effects of SC against CRC by modulating gut microbiota, and uncover potential mechanisms linking SC's therapeutic effects to gut microbiota regulation by analyzing the impact of SC on microbiota composition and CRC progression.<br><br>MATERIAL: This study explores the impact of SC on the gut microbiota in CRC by constructing subcutaneous xenograft tumors of CRC and integrating 16S rRNA sequencing and RNA transcriptomic sequencing. The fecal microbiota transplantation (FMT) mouse model was used to validate the biological function of SC in correcting gut microbiota dysbiosis to treat CRC. Subsequently, we conducted in vitro studies on the molecular mechanisms by which SC regulates the gut microbiota as an effective hallmark of CRC treatment, using lipopolysaccharide (LPS) to simulate an inflammatory gut microbiota environment and P38 MAPK knockdown cell line.<br><br>RESULTS: SC significantly inhibited CRC cell proliferation with IC50 values of 2.547&#xb1;0.256 &#x3bc;M for HCT116 and 2.851&#xb1;0.332 &#x3bc;M for LoVo cells. In vivo experiments demonstrated that SC effectively suppressed tumor growth in xenograft models. 16S rRNA sequencing revealed that SC modulated gut microbiota composition, particularly affecting Bacteroides and Alistipes populations. SC significantly reduced the levels of inflammatory factors and inhibited the MAPK signaling pathway, as evidenced by decreased p-JNK, p-p38 MAPK, and p-NF-&#x3ba;B p65 expression.<br><br>CONCLUSIONS: Current clinical practice still lacks effective therapeutic agents targeting CRC through gut microbiota modulation. This study presents the first evidence that SC, a natural compound, exhibits dual-action therapeutic efficacy against CRC progression by simultaneously modulating gut microbial composition and suppressing MAPK pathway-mediated inflammatory responses. These findings highlight SC's novel therapeutic potential as a promising microbiota-regulating candidate for CRC intervention, offering an innovative approach that bridges microbial ecology with cancer signaling pathways.}, }
@article {pmid40392289, year = {2025}, author = {Piteková, B and Hric, I and Baranovičová, E and Zieg, J and Planet, PJ and Bielik, V}, title = {The effect of fecal microbial transplantation in a pediatric patient after 28 episodes of febrile urinary tract infection.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {}, number = {}, pages = {}, pmid = {40392289}, issn = {1432-198X}, support = {VEGA 1/0313/25//Ministerstvo &#x161;kolstva, vedy, v&#xfd;skumu a &#x161;portu Slovenskej republiky/ ; VEGA 1/0022/26//Ministerstvo &#x161;kolstva, vedy, v&#xfd;skumu a &#x161;portu Slovenskej republiky/ ; APVV-22-0047//Agent&#xfa;ra Ministerstva &#x160;kolstva, Vedy, V&#xfd;skumu a &#x160;portu SR/ ; }, abstract = {Recurrent febrile urinary tract infections (fUTIs) in children can lead to serious complications such as renal scarring and progressive chronic kidney disease (CKD), with growing evidence indicating that gut microbiome dysbiosis may play a key role in their development. Fecal microbial transplantation (FMT) is an established therapeutic approach for restoring gut microbial balance; however, its use in patients with recurrent fUTIs remains limited and underexplored. This case study describes a 10-year-old boy with recurrent fUTIs and CKD secondary to a posterior urethral valve (PUV) anomaly. The patient was administered a total of seven doses of FMT. FMT reduced pathogenic Enterobacteriaceae, increased beneficial short-chain fatty acid (SCFA)-producing genera, and correspondingly raised SCFA levels, indicating restoration of gut microbiota balance. FMT presents an innovative therapeutic option for pediatric patients with recurrent fUTIs, demonstrating outstanding clinical outcomes.}, }
@article {pmid40391506, year = {2025}, author = {Ai, R and Jin, Y and Zhang, F and Cui, B and Ji, G}, title = {Washed microbiota transplantation effectively treats a case of acute severe ulcerative colitis combined with viral myocarditis.}, journal = {Journal of biomedical research}, volume = {}, number = {}, pages = {1-5}, doi = {10.7555/JBR.39.20250036}, pmid = {40391506}, issn = {1674-8301}, abstract = {Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis (UC). Management of myocarditis is primarily supportive, as there are currently no established targeted therapies. Recent studies have increasingly demonstrated the association between gut microbiota and myocarditis. Here, we report a case of acute severe UC complicated by cytomegalovirus (CMV) and Epstein-Barr virus (EBV) co-infections leading to viral myocarditis. The patient experienced rapid remission of both intestinal and cardiac symptoms following washed microbiota transplantation (WMT), suggesting WMT as a potential alternative treatment for these life-threatening conditions.}, }
@article {pmid40390988, year = {2025}, author = {Abdulaal, R and Tlaiss, Y and Jammal, F and Moussbah, TH and Tarchichi, A and Hteit, A and Tlais, M and Nassif, D}, title = {The role of microbiome dysbiosis in cardiovascular disease: Mechanisms and therapeutic implications.}, journal = {Global cardiology science &amp; practice}, volume = {2025}, number = {1}, pages = {e202503}, pmid = {40390988}, issn = {2305-7823}, abstract = {The gut microbiome plays a critical role in cardiovascular disease (CVD) pathogenesis through systemic inflammation, disrupted lipid metabolism, and proatherogenic metabolites like trimethylamine-N-oxide (TMAO). Dysbiosis contributes to increased intestinal permeability, platelet hyperreactivity, and reduced short-chain fatty acids (SCFAs), exacerbating cardiovascular risk. Emerging microbiome-targeted therapies, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary interventions, show promise in mitigating CVD. However, challenges remain in translating these findings into clinical practice due to strain-specific effects and interindividual variability. The gut-heart axis represents a transformative avenue for CVD prevention and management, warranting further research to optimize long-term efficacy and safety.}, }
@article {pmid40390224, year = {2025}, author = {Adedayo, SI and Riethmacher, E}, title = {Emerging New Treatments for Colon Cancer.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673372776250505155945}, pmid = {40390224}, issn = {1875-533X}, abstract = {Colorectal cancer includes cancer of the rectum and colon. It is the primary cause of cancer-related deaths among men under 50 years of age. In 2022, over 1.9 million cases of CRC were reported, resulting in approximately 904,000 deaths worldwide. Factors like smoking, alcohol consumption, obesity, familial history, and inflammation significantly contribute to the risk of CRC development. Additionally, bacterial infections from organisms like Bacteroides fragilis, Fusobacterium nucleatum, and Helicobacter pylori also play a role in increasing this risk. Conventional treatment methods for CRC typically involve surgery/polypectomy, chemotherapy, and radiotherapy. Because of limitations like lack of target specificity, the risk of tumor relapse, and the potential for tumor resistance, there is a growing necessity for more individually tailored treatment strategies to improve the outcomes of patients with CRC. As such, emerging treatments like cancer vaccine, (CAR) T-cells, CAR-NK cells, macrophages, and stem cell engineering (particularly mesenchymal stem cells), dendritic vaccine, siRNA, and miRNA, hold significant promise in enhancing outcomes for CRC patients. Moreover, specific gut microbiomes like Bacteroides fragilis, Streptococcus gallolyticus, Enterococcus faecalis, and Escherichia coli, linked to CRC development, have been identified. Hence, modulating the gut microbiome to potentially enhance responses to CRC in high- -risk populations could be a new line of treatment. This modulation can be accomplished through dietary interventions, prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT). This review summarizes the most promising new emerging treatments in the fight against colon cancer.}, }
@article {pmid40390189, year = {2025}, author = {Krynicka, P and Koulaouzidis, G and Marlicz, W and Koulaouzidis, A}, title = {Innovations in the Diagnosis, treatment, and management of disorders of gut-brain interaction (DGBI).}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1080/17474124.2025.2508967}, pmid = {40390189}, issn = {1747-4132}, abstract = {INTRODUCTION: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are the most prevalent disorders of gut-brain interaction (DGBI), frequently overlapping and associated with complex pathophysiological mechanisms. Increasing evidence implicates gut microbiota alterations in driving symptoms via immune activation, altered motility, gut vascular barrier and gut-brain axis disruption.<br><br>AREAS COVERED: This review explores the role of gut microbiota in FD and IBS pathogenesis and symptomatology. A comprehensive literature search was conducted using PubMed, EMBASE, and Google Scholar databases, including studies published between January 2013 and March 2025. Particular focus is given to microbiota-targeted therapies such as prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). The review also discusses multidimensional treatment strategies combining dietary and lifestyle modification, cognitive-behavioral therapy, and pharmacological neuromodulation. Recent advances in diagnostic methods, including capsule-based microbiota sampling and digital tools for remote psychogastroenterology care, are highlighted.<br><br>EXPERT OPINION: Despite scientific progress, current DGBI management remains insufficiently personalized. Future approaches should integrate individualized microbiota profiling with targeted interventions and utilize innovative diagnostic and digital health technologies to enhance clinical outcomes in FD and IBS.}, }
@article {pmid40390033, year = {2025}, author = {Teng, T and Huang, F and Xu, M and Li, X and Zhang, L and Yin, B and Cai, Y and Chen, F and Zhang, L and Zhang, J and Geng, A and Chen, C and Yu, X and Sui, J and Zhu, ZJ and Guo, K and Zhang, C and Zhou, X}, title = {Microbiota alterations leading to amino acid deficiency contribute to depression in children and adolescents.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {128}, pmid = {40390033}, issn = {2049-2618}, support = {82301714//the National Natural Science Foundation of China/ ; 22425404//the National Natural Science Foundation of China/ ; 82271565//the National Natural Science Foundation of China/ ; 2023TQ0398//the China Postdoctoral Science Foundation/ ; CSTB2023NSCQ-BHX0106//Natural Science Foundation of Chongqing, China/ ; 2208013341918508//Postdoctoral Innovation Talents Support Program of Chongqing, China/ ; 2022YFC3400702//National Key R&amp;D Program of China/ ; 2024YFC2707800//National Key R&amp;D Program of China/ ; 2022ZD0212900//STI2030-Major Projects/ ; }, mesh = {Humans ; Adolescent ; Child ; *Gastrointestinal Microbiome/physiology ; Male ; *Depressive Disorder, Major/microbiology/metabolism ; Female ; *Amino Acids/deficiency/blood/metabolism ; Magnetic Resonance Imaging ; Animals ; Rats ; Brain/diagnostic imaging/metabolism ; Feces/microbiology ; Metagenomics/methods ; Metabolomics/methods ; *Depression/microbiology ; }, abstract = {BACKGROUND: Major depressive disorder (MDD) in children and adolescents is a growing global public health concern. Metabolic alterations in the microbiota-gut-brain (MGB) axis have been implicated in MDD pathophysiology, but their specific role in pediatric populations remains unclear.<br><br>RESULTS: We conducted a multi-omics study on 256 MDD patients and 307 healthy controls in children and adolescents, integrating plasma metabolomics, fecal metagenomics, and resting-state functional magnetic resonance imaging (rs-fMRI) of the brain. KEGG enrichment analysis of 360 differential expressed metabolites (DEMs) indicated significant plasma amino acid (AA) metabolism deficiencies (p-value&#x2009;<&#x2009;0.0001). We identified 58 MDD-enriched and 46 MDD-depleted strains, as well as 6 altered modules in amino acid metabolism in fecal metagenomics. Procrustes analysis revealed the association between the altered gut microbiome and circulating AA metabolism (p-value&#x2009;=&#x2009;0.001, M[2]&#x2009;=&#x2009;0.932). Causal analyses suggested that plasma AAs might mediate the impact of altered gut microbiota on depressive and anxious symptoms. Additionally, rs-fMRI revealed that connectivity deficits in the frontal lobe are associated with depression and 22 DEMs in AA metabolism. Furthermore, transplantation of fecal microbiota from MDD patients to adolescent rats induced depressive-like behaviors and 14 amino acids deficiency in the prefrontal cortex (PFC). Moreover, the dietary lysine restriction increased depression susceptibility in adolescent rats by reducing the expression of excitatory amino acid transporters in the PFC.<br><br>CONCLUSIONS: Our findings highlight that gut microbiota alterations contribute to AAs deficiency, particularly lysine, which plays a crucial role in MDD pathogenesis in children and adolescents. Targeting AA metabolism may offer novel therapeutic strategies for pediatric depression. Video Abstract.}, }
@article {pmid40390010, year = {2025}, author = {Han, J and Meng, X and Kong, H and Li, X and Chen, P and Zhang, XA}, title = {Links between short-chain fatty acids and osteoarthritis from pathology to clinic via gut-joint axis.}, journal = {Stem cell research &amp; therapy}, volume = {16}, number = {1}, pages = {251}, pmid = {40390010}, issn = {1757-6512}, support = {Grant No. 32371184//National Natural Science Foundation of China/ ; No. 2023JH2/101300072//the Liaoning Province Applied Basic Research Program/ ; LJKQZ20222425//the basic scientific research project of higher education institutions of Liaoning Province/ ; }, abstract = {Short-chain fatty acids (SCFAs), the primary metabolites produced by the microbial fermentation of dietary fibers in the gut, have a key role in protecting gut health. Increasing evidence indicates SCFAs can exert effects on distant tissues and organs beyond the gut via blood circulation. Osteoarthritis (OA) is a chronic inflammatory joint disease that severely diminishes the physical function and quality of life. However, effective clinical treatments for OA remain elusive. Recent studies have shown that SCFAs can exert beneficial effects on damaged joints in OA. SCFAs can mitigate OA progression by preserving intestinal barrier function and maintaining the integrity of cartilage and subchondral bone, suggesting that they have substantial potential to be the adjunctive treatment strategy for OA. This review described the SCFAs in the human body and their cellular signaling mechanism, and summarized the multiple effects of SCFAs (especially butyrate, propionate, and acetate) on the prevention and treatment of OA by regulating the gut-joint axis, providing novel insights into their promising clinical applications.}, }
@article {pmid40388727, year = {2025}, author = {Kong, J and Han, X and Wei, C}, title = {Causal relationship between metabolic dysfunction-associated fatty liver disease and endotoxin biomarkers: A Mendelian randomization study.}, journal = {Medicine}, volume = {104}, number = {20}, pages = {e42311}, doi = {10.1097/MD.0000000000042311}, pmid = {40388727}, issn = {1536-5964}, support = {[No. (2022)4].//Shandong Provincial Key Laboratory of Traditional Chinese Medicine/ ; }, mesh = {Humans ; Mendelian Randomization Analysis ; *Non-alcoholic Fatty Liver Disease/genetics/blood ; Biomarkers/blood ; *Lipopolysaccharides/blood ; Genome-Wide Association Study ; Acute-Phase Proteins/genetics ; Obesity ; Carrier Proteins/blood ; Membrane Glycoproteins/blood ; *Metabolic Syndrome/genetics ; Risk Factors ; Triglycerides/blood ; Cholesterol, HDL/blood ; *Endotoxins/blood ; }, abstract = {Although the relationship among lipopolysaccharides (LPS), LPS-binding proteins, and metabolic dysfunction-associated fatty liver disease (MAFLD) is widely studied, no conclusive evidence is available. In this study, we used mendelian randomization (MR) to study the causal relationship of LPS, LPS-binding proteins, and MAFLD. Using bidirectional two-sample MR method, we evaluated data from the genome wide association study; for this analysis, nonalcoholic fatty liver disease (NAFLD), liver fat percentage, and other metabolic syndromes were employed as outcomes. Furthermore, MR analysis mainly involved the inverse variance weighted method. Heterogeneity and pleiotropy tests were also conducted. LPS was found to have a causal relationship with NAFLD, obesity, high density lipoprotein cholesterol, and TG levels. Furthermore, TG levels and LBP had significant causal relationships. This study mainly concluded that LPS is a risk factor for NAFLD, obesity, high density lipoprotein cholesterol, and TG, corroborating it's the LPS role in MAFLD pathogenesis. Hence, optimizing the gut microbiota using proper diet, probiotics, or fecal microbiota transplantation may help to reduce inflammation and (IR), thereby improving lipid and glucose metabolism disorders. Although a causal relationship between TG and LBP was observed, further studies are required to determine a specific mechanism.}, }
@article {pmid40388258, year = {2025}, author = {Ebadpour, N and Abavisani, M and Sahebkar, A}, title = {Microbiome-driven precision medicine: Advancing drug development with pharmacomicrobiomics.}, journal = {Journal of drug targeting}, volume = {}, number = {}, pages = {1-27}, doi = {10.1080/1061186X.2025.2509283}, pmid = {40388258}, issn = {1029-2330}, abstract = {Pharmacomicrobiomics investigates the complicated relationship between the gut microbiome and medications, highlighting how the microbiome affects drug absorption, metabolism, and overall treatment outcomes. The interaction between pharmaceutical agents and the host microbiota is inherently bidirectional and complex. While the administration of various drugs can alter the composition and diversity of the gut microbial community, the intestinal microbiota, in turn, plays a crucial role in modulating fundamental pharmacokinetic and pharmacodynamic processes, which in turn affect the efficacy and safety of drugs. Microbial communities can influence the metabolism and efficacy of many medications in two primary ways: directly and indirectly. Direct mechanisms typically entail the induction of biochemical alterations and multiple transformations directly on the drug, whereas indirect mechanisms encompass modifications in host metabolism, alterations in the gut microbial community, the synthesis of various metabolites, and interactions with the host immune system, which indirectly influence the drug's metabolism, absorption, and efficacy. For instance, microbial communities play an important part in activating prodrugs like sulfasalazine, improving the outcomes of immunotherapy, and minimizing toxicity through specific interventions. Nonetheless, barriers can also emerge from the microbial breakdown of medications, reducing their therapeutic efficacy, along with adverse reactions mediated by microbiota. Innovations like probiotics, fecal microbiota transplantation, and microbiota profiling have shown promise in enhancing these interactions. Utilizing the distinct microbiota composition of individuals, pharmacomicrobiomics offers a route to personalized, precise, and safer therapies, signaling an important evolution in drug development and clinical practice. This study aims to provide a comprehensive overview of microbiome-drug interactions, with a particular focus on the influence of gut microbiota on drug efficacy, and to highlight their potential to revolutionize precision medicine.}, }
@article {pmid40387516, year = {2025}, author = {Kochkarian, T and Nagy, HI and Li, Q}, title = {Gut-Heart Axis: Cardiac Remodeling and Heart Failure in the Context of Inflammatory Bowel Disease and Dysbiosis.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00016.2025}, pmid = {40387516}, issn = {1522-1547}, support = {R01 HL152683/HL/NHLBI NIH HHS/United States ; }, abstract = {Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are debilitating and complex chronic gastrointestinal disorders that affect not only the gut but also extraintestinal organs, including the heart. The gut-heart crosstalk has garnered increasing attention in recent years; however, the molecular mechanisms underlying this complex interplay remain poorly understood. This review explores the gut-heart axis, focusing on how IBD disrupts gut microbiota homeostasis and promotes cardiac remodeling through systemic inflammation and various mediators, ultimately contributing to the onset or progression of heart failure. IBD compromises the integrity of the intestinal barrier, allowing microbial metabolites such as trimethylamine N-oxide and phenylacetylglutamine, along with inflammatory cytokines and microRNAs (miRNA) (e.g., miR-155, miR-21, let-7a), to enter the circulation and contribute to cardiac remodeling and heart failure. We identify dysfunction of nucleotide-binding oligomerization domain-containing protein 2 as a critical link between gut immunity and cardiovascular pathology. Additionally, we discuss emerging microbiome-based therapeutic strategies, including fecal microbiota transplantation and IL-23 inhibitors, aimed at restoring gut homeostasis and mitigating cardiovascular risk. By integrating molecular mechanisms, clinical evidence, and therapeutic approaches, this review underscores the pivotal role of gut dysbiosis in cardiac dysfunction and offers new perspectives for managing cardiac dysfunction in patients with IBD.}, }
@article {pmid40386180, year = {2025}, author = {Fang, Y and Min, S and Wu, Y and Xu, F and Chen, H and Li, Y and Lu, Y and Hu, J and Zhu, L and Shen, H}, title = {Integration of Multi-Omics and Network Pharmacology Analysis Reveals the Mechanism of Qingchang Huashi Jianpi Bushen Formula in Repairing the Epithelial Barrier of Ulcerative Colitis.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {6167-6189}, pmid = {40386180}, issn = {1178-7031}, abstract = {PURPOSE: Derivation of Qingchang Huashi formula, named Qingchang Huashi Jianpi Bushen (QCHS_JPBS) formula, has shown significant therapeutic effect on patients with ulcerative colitis (UC). In this study, the potential mechanism of QCHS_JPBS formula in repairing mucosal damage was explored from the perspective of intestinal stem cell (ISCs) differentiation, and potential targets of the QCHS_JPBS formula to improve UC were predicted using network pharmacology analysis.<br><br>METHODS: The therapeutic efficacy of QCHS_JPBS formula was evaluated in a mouse model of 2.5% dextran sulfate sodium (DSS) induced colitis. The effect of this formula on the ISC differentiation was evaluated using tissue transmission electron microscopy, immunofluorescence, and RT-qPCR. The cecal contents were subjected to 16s RNA sequencing analysis and non-target metabolomics analysis using LC-MS/MS. The fecal microbiota transplantation method verified the essential role of gut microbiota in promoting ISC differentiation and repairing mucosal damage.<br><br>RESULTS: The results indicated that QCHS_JPBS formula suppressed the inflammatory response and repaired the damaged intestinal epithelial barrier in DSS-induced colitis mice. QCHS_JPBS formula promoted ISC differentiation, particularly in the direction of goblet cells. QCHS_JPBS formula restored gut dysbiosis and regulated metabolic disorders in DSS-induced colitis mice. And then, the results of fecal microbiota transplantation indicated that QCHS_JPBS formula promoted differentiation of intestinal stem cells to repair mucosal damage through gut microbiota. Finally, a total of 79 active ingredients of QCHS_JPBS formula were identified based on LC-MS analysis and EGFR, STAT3, SRC, AKT1, and HSP90AA1 were considered as potential therapeutic UC targets of QCHS_JPBS formula based on network pharmacology analysis.<br><br>CONCLUSION: The present study demonstrated that QCHS_JPBS formula promoted the differentiation of ISCs through gut microbiota to repair the damaged intestinal epithelial barrier in UC mice.}, }
@article {pmid40385744, year = {2025}, author = {Truong, MH and Ngo, T and Nguyen, QT and Le, H}, title = {Diagnosis and Treatment Outcomes of Fournier's Gangrene at a Tertiary Hospital.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e82344}, pmid = {40385744}, issn = {2168-8184}, abstract = {Introduction Fournier's gangrene (FG) is a severe necrotizing fasciitis caused by polymicrobial agents. This study aims to evaluate the clinical and paraclinical characteristics, treatment outcomes, and factors related to mortality in patients with FG at People's Hospital 115, Vietnam. Methods A retrospective cohort study was conducted on all adult patients diagnosed with FG at People's Hospital 115 from January 2018 to October 2024. Variables, including sociodemographic, clinical features, laboratory tests, and treatment outcomes, were collected. Data analysis was performed using SPSS version 26.0 (IBM Corp, Armonk, NY, USA). Results A total of 60 patients (47 males and 13 females) were enrolled; the mean age was 58.2 ± 12.6 years. The most common infection origins were from skin infections (36.7%), followed by the gastrointestinal tract (31.7%) and the genitourinary tract (30%). Most patients presented with symptoms such as perineal pain (98.3%), perianal swelling (91.7%), fever (48.3%), lower abdominal fluid collection (43.3%), and purulent discharge or perineal necrosis (31.7%). The most prevalent risk factor was diabetes mellitus (61.8%). Pathogenic bacteria that were commonly Escherichia coli, Klebsiella, and Proteus species could be isolated. Treatment involved both medical management (resuscitation, broad-spectrum antibiotics, and wound care) and surgical interventions (debridement, necrotic tissue excision, and fecal and urinary diversion). The overall mortality rate was 18.3%. Factors significantly associated with mortality included advanced age, female sex, a history of long-term corticosteroid use, high severity index scores, and septic shock. Conclusion FG is an uncommon urological emergency that is a rapidly progressing disease with a high mortality rate. Early detection and aggressive treatment approaches to achieve better outcomes.}, }
@article {pmid40383915, year = {2025}, author = {Kim, YJ and Lee, J and Lee, E and Park, SJ and Kim, JH}, title = {Impact of stool transplantation and metformin on polyp reduction and inflammation in an APC Min mouse model.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2025.00011}, pmid = {40383915}, issn = {1598-9100}, abstract = {BACKGROUND/AIMS: Familial adenomatous polyposis is a hereditary condition characterized by numerous adenomatous polyps in the colon and rectum, significantly increasing colorectal cancer risk. Current management strategies, such as prophylactic colectomy, are invasive and have long-term consequences, highlighting the need for alternative therapies. This study aimed to evaluate whether stool transplantation and metformin therapy synergistically reduce polyp formation and inflammation.<br><br>METHODS: APC Min mice were divided into 4 groups: control, anti-control (antibiotic pretreatment), stool (stool transplantation), and stool+metformin. Polyp burden, bacterial abundance, inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-&#x3b1;, IL-10), and tumorigenic markers (NF-&#x3ba;B, Cox2, c-myc, &#x3b2;-catenin) were assessed using messenger RNA (mRNA) and protein analyses of intestinal tissues, along with serum and fecal microbiota evaluations.<br><br>RESULTS: Stool transplantation combined with metformin significantly reduced bacterial abundance and polyp burden. The anti-control group showed similar reductions, suggesting suppression of gut microbiota re-establishment. TNF-&#x3b1; and IL-10 levels remained unchanged, but a significant increase in IL-6 was observed in the stool+metformin group's intestinal tissues, indicating localized immune activation. Intestinal Cox2 mRNA expression was reduced in the combination group, correlating with polyp suppression. Protein levels of NF-&#x3ba;B, Cox2, and &#x3b2;-catenin showed no significant changes in vivo, while in vitro experiments revealed a decrease in NF-&#x3ba;B and an increase in Cox2, suggesting complex regulation of inflammation-related pathways.<br><br>CONCLUSIONS: Stool transplantation combined with metformin reduces polyp burden in APC Min mice through gut microbiota modulation and localized immune activation. These findings support the therapeutic potential of this combination treatment for familial adenomatous polyposis.}, }
@article {pmid40383790, year = {2025}, author = {Chen, J and Feng, R and Gong, BB and Wu, WK and Dai, BS and Tan, R and Xu, WL and Meng, T and Wang, XB and Xiao, YZ and Yang, C and Zhang, L and Liang, CZ}, title = {High-salt-driven gut microbiota dysfunction aggravates prostatitis by promoting AHR/SGK1/FOXO1 axis-mediated Th17 cell differentiation.}, journal = {Military Medical Research}, volume = {12}, number = {1}, pages = {21}, pmid = {40383790}, issn = {2054-9369}, support = {82300872//National Natural Science Foundation of China/ ; 82170787//National Natural Science Foundation of China/ ; T000529//Supporting Projects for Innovative Leading Talents/ ; 2021-108-10//Distinguished Young Scholar of Anhui Colleges/ ; 2022AH020073//Science Foundation for Outstanding Young Scholar of Anhui Colleges/ ; SZSM20210300//Sanming Project of Medicine in Shenzhen Nanshan/ ; 2408085Y038//Anhui Provincial Natural Science Foundation/ ; }, mesh = {Male ; Animals ; Mice ; *Prostatitis/physiopathology/etiology ; *Gastrointestinal Microbiome/drug effects/physiology ; *Th17 Cells/metabolism/drug effects ; Receptors, Aryl Hydrocarbon/metabolism ; Humans ; Cell Differentiation/drug effects ; Protein Serine-Threonine Kinases/metabolism ; Immediate-Early Proteins/metabolism ; Sodium Chloride, Dietary/adverse effects ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a frequently encountered disorder characterized by voiding symptoms and pelvic or perineal pain. Proinflammatory T helper 17 (Th17) cells are essential for triggering the development of CP/CPPS. High-salt diet (HSD) consumption has been found to cause an accumulation of sodium chloride in peripheral organs, inducing autoimmune responses via the Th17 cell axis. It is currently unknown whether HSD affects the etiology and course of CP/CPPS.<br><br>METHODS: Patients diagnosed with CP/CPPS were evaluated with the National Institutes of Health Chronic Prostatitis Symptom Index scoring system, and the correlation between the symptoms of CP/CPPS with HSD was analyzed. The experimental autoimmune prostatitis (EAP) mouse was established and the mice were fed either a normal-salt diet (NSD) or HSD for 6&#xa0;weeks to investigate the impact of HSD on CP/CPPS. Then, 16S ribosomal RNA sequencing and untargeted metabolomics were introduced to detect the differences in the gut microflora composition and metabolite profiles between NSD-fed and HSD-fed mice, followed by fecal microbiota transplantation, 5-hydroxyindole acetic acid (5-HIAA) supplementation, aryl hydrocarbon receptor (AHR) inhibition, and in vitro Th17 differentiation experiments, which were performed to explore the mechanisms underlying HSD-aggravated CP/CPPS. Finally, chromatin immunoprecipitation assay and quantitative polymerase chain reaction were conducted to validate whether AHR can serve as a transcription factor by interacting with the serum and glucocorticoid-regulated kinase 1 (Sgk1) promoter in CD4[+] T cells.<br><br>RESULTS: Increased salt consumption had a positive correlation with symptom scores of CP/CPPS patients, which was validated by feeding EAP mice with HSD, and HSD worsened the prostate inflammation and tactile allodynia in EAP mice through promoting the differentiation of CD4[+] T cells to Th17 cells. HSD exacerbated EAP by significantly reducing the relative abundance of beneficial gut microflora, such as Lactobacillaceae, and gut microbiota metabolite 5-HIAA, which is related to tryptophan metabolism. The prostate inflammation, tactile allodynia, and proportion of Th17 cells in mice that received fecal suspensions from the EAP&#x2009;+&#x2009;HSD group were significantly more severe or higher than those in mice that received fecal suspensions from the EAP&#x2009;+&#x2009;NSD group. However, 5-HIAA supplementation ameliorated the symptoms of EAP caused by HSD through inhibiting the differentiation of CD4[+] T cells to Th17 cells, while AHR inhibition abrogated the protective effects of 5-HIAA supplementation on EAP mice fed a HSD through promoting the differentiation of CD4[+] T cells to Th17 cells. Mechanistically, it has been revealed that the SGK1/forkhead box protein O1 (FOXO1) pathway was significantly activated during cytokine-induced Th17 cell differentiation, and AHR has been shown to inhibit SGK1 transcription by interacting with the Sgk1 promoter in CD4[+] T cells to inhibit FOXO1 phosphorylation, consequently restoring the equilibrium of Th17 cell differentiation.<br><br>CONCLUSION: Our findings indicated that high salt intake represented a risk factor for the development of CP/CPPS as it promoted the differentiation of CD4[+] T cells to Th17 cells through the 5-HIAA/AHR/SGK1/FOXO1 axis, which might be a potential therapeutic target for CP/CPPS.}, }
@article {pmid40383397, year = {2025}, author = {Merrick, B and Prossomariti, D and Allen, E and Bisnauthsing, K and Kertanegara, M and Sergaki, C and Le Guennec, AD and Delord, M and Bell, JT and Conte, MR and Moyes, DL and Shankar-Hari, M and Douiri, A and Goodman, AL and Shawcross, DL and Goldenberg, SD}, title = {Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO): a feasibility randomised controlled trial.}, journal = {The Journal of infection}, volume = {}, number = {}, pages = {106504}, doi = {10.1016/j.jinf.2025.106504}, pmid = {40383397}, issn = {1532-2742}, abstract = {OBJECTIVES: The gastrointestinal tract (GIT) is a reservoir of multidrug-resistant organisms (MDRO). Colonisation with MDRO precedes invasive infections which can be challenging to treat with excess morbidity and mortality compared to antimicrobial susceptible infections. Currently, there are no effective GIT decolonisation strategies. Whilst Faecal Microbiota Transplant (FMT) has emerged as a potential therapeutic, there remains uncertainty about its feasibility, safety and efficacy.<br><br>METHODS: Population: Patients with invasive infection with Extended-spectrum Beta-Lactamase (ESBL-) or Carbapenem-resistant Enterobacterales (CRE) and persistent GIT carriage.<br><br>INTERVENTION: Three doses of encapsulated lyophilised FMT.<br><br>COMPARATOR: Matched placebo capsules.<br><br>OUTCOMES: Primary outcome was participant consent rate as a proportion of those approached to be screened for GIT carriage of ESBL-E/CRE. Secondary outcomes were additional feasibility, safety and tolerability, and efficacy metrics. Exploratory outcomes included stool metagenomic analysis.<br><br>RESULTS: Of 460 approached individuals, 124 (27%) consented. 53/124 participants (43%) fulfilled all eligibility criteria. 44/53 (83%) of those eligible were randomised and 41/44 (93%) received investigational medicinal product (IMP): 20 FMT and 21 placebo. 39/41 (95%) completed IMP dosing. Abdominal bloating and skin and subcutaneous tissue disorders were more common following FMT but there were no unanticipated harms. MDRO carriage decreased over time across arms but was lower at all time points in the FMT arm. FMT increased microbiome diversity and microbiome-based health measures. FMT recipients' samples clustered into two groups with those with more dissimilar community composition to donors more likely to decolonise post-FMT (3/5 vs. 0/12, p=0.01). Patients that decolonised exhibited a trend towards increased proportional representation of donor-derived strains in their post-FMT samples (p=0.05) and change in strain dominance within MDRO at species-level.<br><br>CONCLUSIONS: Progression to a substantive trial is feasible with modifications to the existing FERARO protocol. FMT was safe, well tolerated, and acceptable to patients colonised with MDRO. Microbiome analysis infers that greater donor-recipient microbiome dissimilarity at baseline and higher rates of donor-derived strain engraftment favour MDRO decolonisation, which in turn maybe facilitated by conspecific strain replacement.}, }
@article {pmid40383206, year = {2025}, author = {Stensvold, CR and Tomiak, J and Seyoum, Y and Nielsen, HV and van der Giezen, M}, title = {Letter to the Editor: Comment to "Assessment of Dientamoeba fragilis interhuman transmission by fecal microbiota transplantation" by Moreno-Sabater et al. (2025).}, journal = {International journal of antimicrobial agents}, volume = {}, number = {}, pages = {107541}, doi = {10.1016/j.ijantimicag.2025.107541}, pmid = {40383206}, issn = {1872-7913}, }
@article {pmid40381961, year = {2025}, author = {Zhao, X and Lei, C and Wang, Y and Zhang, L and Tang, W and Li, Z and Jiang, L and Li, X}, title = {Impact of TLR5 Overexpression on Gut Microbiota and Metabolites: Insights into Salmonella Infection Outcomes.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {107708}, doi = {10.1016/j.micpath.2025.107708}, pmid = {40381961}, issn = {1096-1208}, abstract = {BACKGROUND: The gut microbiome and the host immune system work together to maintain intestinal health and protect against infections. Toll-like receptor 5 (TLR5) recognizes bacterial flagellin and plays a crucial role in this network. However, the precise role of TLR5 in regulating gut microbiota and resistance to infection remains unclear. This study utilized a TLR5 intestine-specific overexpression mouse model to explore these interactions and their impact on Salmonella infection.<br><br>METHODS: TLR5 intestine-specific overexpression mice (TLR5+/+) and wild-type (WT) mice were infected with Salmonella to assess TLR5's protective role. Survival time, fecal Salmonella load, and intestinal tissue integrity were evaluated. Subsequently, 16S rRNA sequencing and LC-MS-based metabolomics were performed to analyze gut microbiota composition and fecal metabolites. Fecal microbiota transplantation (FMT) and metabolite transplantation experiments were conducted to evaluate the functional impact of microbiota and metabolites on resistance to infection.<br><br>RESULTS: TLR5 overexpression significantly improved survival time and reduced fecal Salmonella load, demonstrating its protective role against infection. 16S rRNA sequencing revealed enrichment of beneficial taxa, while metabolomic analysis identified altered metabolites in TLR5+/+ mice. Although fecal microbiota and metabolite transplantation did not fully replicate the protective effects, these experiments highlighted the important roles of microbiota and metabolites in infection outcomes, with limitations in transplantation likely affecting the results. These findings underscore the significance of microbiota and metabolites in TLR5-mediated gut immunity.<br><br>CONCLUSION: TLR5 overexpression significantly alters gut microbiota and metabolite profiles, contributing to improved infection outcomes. These findings highlight the critical roles of microbiota and metabolites in TLR5-mediated immunity and provide a foundation for exploring targeted strategies to enhance resistance against enteric pathogens.}, }
@article {pmid40381958, year = {2025}, author = {Bolte, LA and Björk, JR and Gacesa, R and Weersma, RK}, title = {Pharmacomicrobiomics: The role of the gut microbiome in immunomodulation and cancer therapy.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2025.04.025}, pmid = {40381958}, issn = {1528-0012}, abstract = {There is a large heterogeneity among individuals in their therapeutic responses to the same drug and in the occurrence of adverse events. A key factor increasingly recognized to contribute to this variability is the gut microbiome. The gut microbiome can be regarded as a second genome, holding significant metabolic capacity. Consequently, the field of pharmacomicrobiomics has emerged as a natural extension of pharmacogenomics for studying variations in drug responses. Pharmacomicrobiomics explores the interaction of microbiome variation with drug response and disposition. The interaction between microbes and drugs is, however, complex and bidirectional. While drugs can directly alter microbial growth or influence gut microbiome composition and functionality, the gut microbiome also modulates drug responses directly through enzymatic activities and indirectly via host-mediated immune and metabolic mechanisms. Here we review recent studies that demonstrate the interaction between drugs and the gut microbiome, focusing on cancer immunotherapy and immunomodulation in the context of inflammatory bowel disease and solid organ transplantation. Since the gut microbiome is modifiable, pharmacomicrobiomics presents promising opportunities for optimizing therapeutic outcomes, with recent clinical trials highlighting fecal microbiota transplantation as a strategy to enhance the efficacy of immune checkpoint blockade. We also shed light on the future perspectives for patients arising from this field. While multiple lines of evidence already demonstrate that the gut microbiome interacts with drugs, and vice versa, thereby affecting treatment efficacy and safety, well-designed clinical studies and integrated in vivo and ex vivo models are necessary to obtain consistent results, improve clinical translation and further unlock the gut microbiome's potential to improve drug responses.}, }
@article {pmid40381872, year = {2025}, author = {Barlowe, TS and Desai, S and Sanderford, AE and Holowka, T and Peery, AF and McGill, SK}, title = {Fulminant Clostridioides difficile Infection Following Fecal Microbiota Spores compared to Fecal Microbiota Transplant.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2025.03.027}, pmid = {40381872}, issn = {1542-7714}, }
@article {pmid40381501, year = {2025}, author = {Jia, Y and Liu, X and Gao, X and Yin, S and Wu, K and Meng, X and Ren, H and Liu, J and Liu, Z and Li, H and Jiang, Y}, title = {Plantamajoside alleviates DSS-induced ulcerative colitis by modulating gut microbiota, upregulating CBS, and inhibiting NF-κB.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {143}, number = {}, pages = {156827}, doi = {10.1016/j.phymed.2025.156827}, pmid = {40381501}, issn = {1618-095X}, abstract = {BACKGROUND: Plantamajoside (PMS) is a natural bioactive compound derived from medicinal, food homologous plants of the genus Plantago.<br><br>PURPOSE AND METHODS: This study aimed to investigate the protective effects of PMS on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and explore the associated mechanisms.<br><br>RESULTS: We found that PMS treatment significantly alleviated UC symptoms in mice by preventing body weight loss, increasing colon length, and reducing disease activity index scores. Moreover, PMS alleviated colonic lesions, increased the number of goblet cells, upregulated the expression of intestinal barrier proteins (ZO-1, occludin, and claudin-3), and decreased the levels of pro-inflammatory factors. PMS treatment modulated the gut microbiota by increasing the relative abundance of Bacteroidota and Verrucomicrobiota and decreasing that of Firmicutes and Proteobacteria at the phylum level. At the genus level, PMS suppressed the abundance of pathogenic bacteria, such as Turicibacter and upregulated the abundance of [Eubacterium]_xylanophilum_group. Fecal microbiota transplantation experiments further confirmed that PMS treatment alleviated UC by modulating the gut microbiota. Transcriptomic analysis of colon tissues, coupled with reverse transcription-quantitative polymerase chain reaction and western blotting, showed that PMS treatment upregulated cystathionine beta-synthase (CBS) expression and inhibited NF-&#x3ba;B pathway activation. In a lipopolysaccharide-induced inflammation model in RAW264.7 cells, PMS treatment inhibited the secretion of pro-inflammatory cytokines, upregulated CBS expression, and prevented NF-&#x3ba;B pathway activation.<br><br>CONCLUSION: PMS protects against UC in mice via multiple mechanisms, including modulating the gut microbiota, increasing the expression levels of CBS, and inhibiting the NF-&#x3ba;B pathway.}, }
@article {pmid40380157, year = {2025}, author = {Deng, M and Li, X and Wu, H and Xue, D and Wang, Y and Guo, R and Cui, Y and Jin, C and Luo, F and Li, H}, title = {The current status and prospects of gut microbiota combined with PD-1/PD-L1 inhibitors in the treatment of colorectal cancer: a review.}, journal = {BMC gastroenterology}, volume = {25}, number = {1}, pages = {380}, pmid = {40380157}, issn = {1471-230X}, support = {2021XM22//Key Research and Development (R&amp;D) Projects of Shanxi Province/ ; 202103021224346//Fundamental Research Program of Shanxi Province/ ; }, mesh = {*Colorectal Neoplasms/therapy/microbiology/genetics ; *Gastrointestinal Microbiome ; Humans ; *Immune Checkpoint Inhibitors/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; B7-H1 Antigen/antagonists &amp; inhibitors ; Microsatellite Instability ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor. Immune checkpoint inhibitors (ICIs), particularly those targeting programmed cell death protein 1(PD-1) and programmed cell death ligand 1(PD-L1), have shown promising potential in the treatment of CRC. Specific gut microbiota can modulate the efficacy of ICIs through immune or metabolic pathways. This review summarizes recent advances in the combined application of gut microbiota and PD-1/PD-L1 inhibitors in the treatment of CRC, aiming to provide insights for expanding clinical treatment options for CRC.<br><br>MATERIALS AND METHODS: We employed a systematic search strategy to screen relevant literature from databases such as PubMed, EMBASE, Medline, Cochrane Library, and Clinical Trial registries, with the search period covering from the inception of each database to October 2024. This study includes animal models and human trial subjects. Data extraction and literature screening were strictly carried out by two independent researchers.<br><br>RESULTS: A total of 8 animal studies and 5 clinical trials were included to evaluate the effects of gut microbiota combined with PD-1/PD-L1 inhibitors in CRC. Tumor types included Microsatellite Stability(MSS), Microsatellite Instability-Low(MSI-L), and MSI-H CRC. Main outcomes were tumor volume, weight, and incidence; one study reported survival. Study durations ranged from 20 days to 26 weeks. Two studies used human fecal microbiota transplantation(FMT), and six applied experimental microbial interventions. The 5 clinical trials used ORR as the primary endpoint.Some also reported DCR, PFS, and OS. Two studies targeted Microsatellite Instability-High(MSI-H)/Deficient Mismatch Repair(dMMR), two MSS/Proficient Mismatch Repair(pMMR), and one lacked molecular subtype specification. All trials used full microbiota transplantation; one has released preliminary data.<br><br>CONCLUSION: The treatment regimen combining gut microbiota with PD-1/PD-L1 inhibitors has shown promising therapeutic prospects in both animal studies and clinical research, although most clinical trials are data remain limited. Future studies should focus on: (1) gene-edited probiotic strains with targeted modifications; (2) the synergistic effects of multiple probiotics; and (3) conducting high-quality, multicenter clinical trials.}, }
@article {pmid40376856, year = {2025}, author = {Takyi, E and Nirmalkar, K and Adams, J and Krajmalnik-Brown, R}, title = {Interventions targeting the gut microbiota and their possible effect on gastrointestinal and neurobehavioral symptoms in autism spectrum disorder.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2499580}, doi = {10.1080/19490976.2025.2499580}, pmid = {40376856}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Autism Spectrum Disorder/therapy/microbiology ; Probiotics/therapeutic use/administration &amp; dosage ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; *Gastrointestinal Diseases/therapy/microbiology ; Gastrointestinal Tract/microbiology ; Child ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Autism spectrum disorder (ASD) is a developmental disorder that is characterized by deficits in social communication and restricted, repetitive, and stereotyped behaviors. In addition to neurobehavioral symptoms, children with ASD often have gastrointestinal symptoms (e.g. constipation, diarrhea, gas, abdominal pain, reflux). Several studies have proposed the role of gut microbiota and metabolic disorders in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients; these results offer promising avenues for novel treatments of this disorder. Interventions targeting the gut microbiota - such as fecal microbiota transplant (FMT), microbiota transplant therapy (MTT), probiotics, prebiotics, synbiotics, antibiotics, antifungals, and diet - promise to improve gut health and can potentially improve neurological symptoms. The modulation of the gut microbiota using MTT in ASD has shown beneficial and long-term effects on GI symptoms and core symptoms of autism. Also, the modulation of the gut microbiota to resemble that of typically developing individuals seems to be the most promising intervention. As most of the studies carried out with MTT are open-label studies, more extensive double-blinded randomized control trials are needed to confirm the efficacy of MTT as a therapeutic option for ASD. This review examines the current clinical research evidence for the use of interventions that target the microbiome - such as antibiotics, antifungals, probiotics/prebiotics, synbiotics, and MTT - and their effectiveness in changing the gut microbiota and improving gastrointestinal and neurobehavioral symptoms in ASD.}, }
@article {pmid40375906, year = {2025}, author = {Finotto, T and Chevenet, C and Fayard, A}, title = {Fecal Microbiota Transplantation as a Salvage Therapy for Concomitant Resistant Digestive Graft Versus Host Disease and Cryptosporidiosis in a Patient Post Hematopoietic Stem Cell Transplant: about a Case.}, journal = {Mediterranean journal of hematology and infectious diseases}, volume = {17}, number = {1}, pages = {e2025035}, pmid = {40375906}, issn = {2035-3006}, }
@article {pmid40375326, year = {2025}, author = {Liu, J and Zhang, D and Zhou, Y and Wu, J and Feng, W and Peng, C}, title = {Fuzi alleviates cold-related rheumatoid arthritis via regulating gut microbiota and microbial bile acid metabolism.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {64}, pmid = {40375326}, issn = {1749-8546}, support = {82104409//National Natural Science Foundation of China/ ; 82304850//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Rheumatoid arthritis (RA) with cold pattern is an important type of RA according to the theory of traditional Chinese medicine. Fuzi (also known as the lateral roots of Aconitum carmichaelii Debx.) represents a typical traditional Chinese medicine that has been clinically used for treatment of the RA especially cold-related RA for thousands of years, yet its mechanism remains unknown.<br><br>PURPOSE: The purpose of the research was to study the therapeutic effects of Fuzi on cold-related RA, and to investigate the mechanism of its action.<br><br>METHODS: Here, we investigated the pharmacological effects of Fuzi on cold-related RA using micro-CT, histopathological analysis, and inflammatory cytokine test. Then, a gut microbiota composition analysis in combination with fecal microbiota transplantation were used to confirm the role of gut microbiota in the therapeutic effects of Fuzi. Further, targeted bile acid metabolomics was used to screen the possible differential microbial bile acids involved in the mechanism of Fuzi. In vitro bioactivity analysis of differential bile acids was used to assess their anti-inflammation activity. Finally, western blot was used to investigate the signaling pathways of Fuzi in reducing the inflammation of cold-related RA.<br><br>RESULTS: The results showed that Fuzi alleviates cold-related RA by improving arthritis index, paw swelling, bone damage, and inflammatory cytokines. In addition, the ameliorative effect of Fuzi is dependent on gut microbiota such as the taxa Lachnospiraceae and Ruminococcaceae. Targeted analysis of fecal and serum bile acids showed that TCA and THDCA were the main differential metabolites. In vitro, TCA and THDCA showed anti-inflammation effects on RAW264.7 cells. Western blot showed that Fuzi regulates TGR5-cAMP-PKA signaling and NLRP3 inflammasome to reduce cold-related arthritis.<br><br>CONCLUSION: Overall, our results demonstrated that Fuzi could regulate gut microbiota and microbial bile acid metabolism, the microbial metabolite THDCA acts on TGR5-cAMP-PKA signaling pathway and NLRP3 inflammasome to reduce cold-related arthritis. Our study suggests that supplementation of Fuzi or THDCA can be of great value for the prevention and clinical treatment of cold-related RA.}, }
@article {pmid40375187, year = {2025}, author = {Bai, XJ and Mei, YC and Zhao, JT and Chen, ZR and Yang, CX and Dong, XJ and Yu, JW and Xiang, LB and Zhou, EZ and Chen, Y and Hao, JY and Zhang, ZJ and Liuyang, YX and Ren, L and Yao, YM and Zhang, L and Lv, Y and Lu, Q}, title = {Changes in microbiome composition after fecal microbiota transplantation via oral gavage and magnetic navigation technology-assisted proximal colon/cecum enema in antibiotic knock-down rats: a comparative experimental study.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {295}, pmid = {40375187}, issn = {1471-2180}, support = {92048202//Major Research Plan of the National Natural Science Foundation of China/ ; 2021GXLH-Z-047//Key R&amp;D Plan of Shaanxi Province/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Rats ; Feces/microbiology ; *Gastrointestinal Microbiome ; Rats, Sprague-Dawley ; *Colon/microbiology ; *Enema/methods ; Male ; *Cecum/microbiology ; Anti-Bacterial Agents ; *Bacteria/classification/genetics/isolation &amp; purification ; RNA, Ribosomal, 16S/genetics ; Administration, Oral ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) transfers fecal matter from a donor into the gastrointestinal tract of a recipient to induce changes to the gut microbiota for therapeutic benefit; however, differences in the composition of gut microbiota after FMT via different donor material delivery routes are poorly understood. In this study, we first developed a novel technique for FMT, magnetic navigation technology(MAT)-assisted proximal colon enemas, in healthy Sprague-Dawley rats. Besides, the difference in fecal microbiota composition after FMT via oral gavage and proximal colon/cecum enemas was determined in antibiotic knock-down rats, in addition to the impact on intestinal barrier function.<br><br>METHODS: A device consisting of an external magnet and a magnet-tipped 6 Fr tube was used in the MAT group (n&#x2009;=&#x2009;6), and the control group (n&#x2009;=&#x2009;6) where fecal matter was delivered without magnetic navigation. The feasibility and safety of this method were assessed by angiography and histology. Next, the fecal microbiota of donor rats was transplanted into antibiotic knock-down rats via oral gavage (n&#x2009;=&#x2009;6) and MAT-assisted proximal colon/cecum enema (n&#x2009;=&#x2009;6) for a week. Analysis of fecal 16&#xa0;S rRNA was conducted to determine differences in the composition of gut microbiota between different groups. The rat intestinal barrier integrity were evaulated by H&amp;E and ZO-1/MUC2 immunofluorescence staining.<br><br>RESULTS: The end of the fecal tube could be placed in the cecum or proximal colon of rats in MAT group; however, this was rarely achieved in the control group. No colon perforation or bleeding was detected in either group. After fecal microbiota transplantation, the microbiota &#x3b1;-diversity and &#x3b2;-diversity were comparable among the different delivery routes.At the family level, the relative abundances of Muribaculaceae, Oscillospiraceae, and Erysipelotrichaceae were higher in the gavage treatment group, whereas Lactobacillaceae and Saccharimonadaceae were higher in the enema treatment group (all p&#x2009;<&#x2009;0.05). FMT by enema was superior to gavage in maintaining the integrity of the rat intestinal barrier, as assessed by an elevation in the density of goblet cells and increased expression of mucin-2.<br><br>CONCLUSIONS: Fecal microbiota tube placement using magnetic navigation was safe and feasible in rats.Different delivery route for FMT affects the gut microbiota composition and the integrity of the rat intestinal barrier. Future experimental designs should consider the colonization outcomes of critical microbial taxa to determine the optimal FMT delivery routes in scientific research as well as clinical practise.}, }
@article {pmid40373043, year = {2025}, author = {Cassir, N and Benech, N and Galperine, T and Alric, L and Scanzi, J and Bleibtreu, A and Kapel, N and Sokol, H}, title = {A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection: The Failure of a Procedure, not of a Therapy.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf249}, pmid = {40373043}, issn = {1537-6591}, }
@article {pmid40371968, year = {2025}, author = {Jansen, D and Deleu, S and Caenepeel, C and Marcelis, T and Simsek, C and Falony, G and Machiels, K and Sabino, J and Raes, J and Vermeire, S and Matthijnssens, J}, title = {Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2499575}, doi = {10.1080/19490976.2025.2499575}, pmid = {40371968}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy/virology/microbiology ; *Virome ; Male ; Female ; Feces/virology ; Adult ; Gastrointestinal Microbiome ; Middle Aged ; *Bacteriophages/genetics/isolation &amp; purification/classification ; Young Adult ; }, abstract = {Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent colonic inflammation. Standard treatments focus on controlling inflammation but remain ineffective for one-third of patients. This underscores the need for alternative approaches, such as fecal microbiota transplantation (FMT), which transfers healthy donor microbiota to patients. The role of viruses in this process, however, remains underexplored. To address this, we analyzed the gut virome using metagenomic sequencing of enriched viral particles from 320 longitudinal fecal samples of 44 patients enrolled in the RESTORE-UC FMT trial. Patients were treated with FMTs from healthy donors (allogenic, treatment) or themselves (autologous, control). We found that colonic inflammation, both its presence and location, had a greater impact on the gut virome than FMT itself. In autologous FMT patients, the virome was unstable and showed rapid divergence over time, a phenomenon we termed virome drift. In allogenic FMT patients, the virome temporarily shifted toward the healthy donor, lasting up to 5 weeks and primarily driven by microviruses. Notably, two distinct virome configurations were identified and linked to either healthy donors or patients. In conclusion, inflammation strongly affects the gut virome in UC patients, which may lead to instability and obstruct the engraftment of allogeneic FMT.}, }
@article {pmid40371237, year = {2025}, author = {Singh, A and Young, E and Maurya, A and Rajagopalan, A}, title = {Nasogastric Delivery of Fecal Microbiota Transplantation for the Treatment of Fulminant Clostridioides difficile Infection: A Case Report.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {9}, number = {5}, pages = {e70177}, pmid = {40371237}, issn = {2397-9070}, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) is a significant cause of antibiotic-associated diarrhea with high morbidity and mortality, particularly in cases of fulminant disease. Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating severe and refractory CDI, typically administered via colonoscopy. However, in cases complicated by toxic megacolon, alternative methods of FMT delivery may be necessary.<br><br>CASE REPORT: This case report describes a 46-year-old female with cirrhosis and fulminant CDI complicated by toxic megacolon. Due to the patient's hemodynamic instability and contraindications to endoscopic FMT delivery, a novel approach of nasogastric FMT administration was utilized. The patient received a combination of enema-delivered and nasogastric FMT alongside standard antibiotic therapy. This approach resulted in rapid clinical improvement, with resolution of toxic megacolon, normalization of inflammatory markers, and avoidance of colectomy.<br><br>DISCUSSION: This report highlights the successful use of nasogastric FMT in a patient with fulminant CDI, offering a potential alternative delivery route when colonoscopic administration is contraindicated. To our knowledge, this is the first reported case of nasogastric FMT successfully resolving C. difficile-associated toxic megacolon.}, }
@article {pmid40370465, year = {2025}, author = {Cui, X and Li, C and Zhong, J and Liu, Y and Xiao, P and Liu, C and Zhao, M and Yang, W}, title = {Gut microbiota - bidirectional modulator: role in inflammatory bowel disease and colorectal cancer.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1523584}, pmid = {40370465}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Colorectal Neoplasms/microbiology/immunology/therapy/etiology ; *Inflammatory Bowel Diseases/microbiology/immunology/therapy/etiology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {The gut microbiota is a diverse ecosystem that significantly impacts human health and disease. This article focuses on how the gut microbiota interacts with inflammatory bowel diseases and colorectal tumors, especially through immune regulation. The gut microbiota plays a role in immune system development and regulation, while the body's immune status can also affect the composition of the microbiota. These microorganisms exert pathogenic effects or correct disease states in gastrointestinal diseases through the actions of toxins and secretions, inhibition of immune responses, DNA damage, regulation of gene expression, and protein synthesis. The microbiota and its metabolites are essential in the development and progression of inflammatory bowel diseases and colorectal tumors. The complexity and bidirectionality of this connection with tumors and inflammation might render it a new therapeutic target. Hence, we explore therapeutic strategies for the gut microbiota, highlighting the potential of probiotics and fecal microbiota transplantation to restore or adjust the microbial community. Additionally, we address the challenges and future research directions in this area concerning inflammatory bowel diseases and colorectal tumors.}, }
@article {pmid40369623, year = {2025}, author = {Hu, J and Liu, D and Liao, G and Guo, Y and Li, M and Liao, J and Chen, H and Zhou, S and Yang, S and Li, S and Liu, Y and Zhao, M}, title = {Fecal microbiota transplantation alleviates immunosuppressant-associated diarrhea and recurrent urinary tract infection in kidney transplant recipients: a retrospective analysis.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {28}, pmid = {40369623}, issn = {1757-4749}, abstract = {BACKGROUND: Immunosuppressant administration subsequent to organ transplantation exerts a substantial influence on gut microbiota composition, thereby affecting patients' prognosis and quality of life.<br><br>METHODS AND RESULTS: We conducted a retrospective analysis involving 18 patients who experienced severe diarrhea or recurrent urinary tract infection (rUTI) due to prolonged immunosuppressant usage after kidney transplantation. Following episodes of severe diarrhea or rUTI, these individuals underwent fecal microbiota transplantation (FMT), resulting in notable alleviation of clinical symptoms. No unexpected adverse or serious adverse events were reported. In comparison to the pre-FMT period, the &#x3b1;-diversity of the intestinal microbiota in patients did not exhibit a significant difference following FMT; however, there was a notable distinction in the &#x3b2;-diversity and analysis of similarity (ANOSIM). In addition, our findings indicated a significant decline in the relative abundance of the bacterial genera Veillonella, Enterococcus, and Oribacterium, whereas a marked elevation was observed in the relative abundance of Faecalibacterium, Roseburia, Sutterella, Parasutterella, and Ruminiclostridium 5 after FMT in patients. Furthermore, there was a notable alteration in the metabolic pathway of gut microbiota in patients following FMT, with a significant enrichment observed in pathways such as Flavone and flavonol biosynthesis, Cytoskeleton proteins, Chromosome-related processes, NOD-like receptor signaling pathway, Progesterone-mediated oocyte maturation, and Antigen processing and presentation.<br><br>CONCLUSION: FMT exhibited an effective approach for managing rUTI and diarrhea arising from postoperative immunosuppressant exposure in kidney transplant recipients.}, }
@article {pmid40155609, year = {2025}, author = {Rodriguez, J and Cordaillat-Simmons, M and Pot, B and Druart, C}, title = {The regulatory framework for microbiome-based therapies: insights into European regulatory developments.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {53}, pmid = {40155609}, issn = {2055-5008}, mesh = {Humans ; *Microbiota ; Europe ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *Biological Therapy/methods ; }, abstract = {The emergence of a broad spectrum of microbiome-based therapies has triggered changes in European regulatory frameworks. The first part of the review describes these innovative therapies. The second part provides an overview of the current framework and key changes introduced by the Regulation on substances of human origin (SoHO) for the development of microbiome-based therapies, highlighting the need of microbiome regulatory science to unlock the full potential of microbiome-based therapies.}, }
@article {pmid40369317, year = {2025}, author = {Gao, YQ and Tan, YJ and Fang, JY}, title = {Roles of the gut microbiota in immune-related adverse events: mechanisms and therapeutic intervention.}, journal = {Nature reviews. Clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {40369317}, issn = {1759-4782}, abstract = {Immune checkpoint inhibitors (ICIs) constitute a major breakthrough in the field of cancer therapy; their use has resulted in improved outcomes across various tumour types. However, ICIs can cause a diverse range of immune-related adverse events (irAEs) that present a considerable challenge to the efficacy and safety of these treatments. The gut microbiota has been demonstrated to have a crucial role in modulating the tumour immune microenvironment and thus influences the effectiveness of ICIs. Accumulating evidence indicates that alterations in the composition and function of the gut microbiota are also associated with an increased risk of irAEs, particularly ICI-induced colitis. Indeed, these changes in the gut microbiota can contribute to the pathogenesis of irAEs. In this Review, we first summarize the current clinical challenges posed by irAEs. We then focus on reported correlations between alterations in the gut microbiota and irAEs, especially ICI-induced colitis, and postulate mechanisms by which these microbial changes influence the occurrence of irAEs. Finally, we highlight the potential value of gut microbial changes as biomarkers for predicting irAEs and discuss gut microbial interventions that might serve as new strategies for the management of irAEs, including faecal microbiota transplantation, probiotic, prebiotic and/or postbiotic supplements, and dietary modulations.}, }
@article {pmid40368261, year = {2025}, author = {Murayama, R and Cai, Y and Nakamura, H and Hashimoto, K}, title = {Demyelination in Psychiatric and Neurological Disorders: Mechanisms, Clinical Impact, and Novel Therapeutic Strategies.}, journal = {Neuroscience and biobehavioral reviews}, volume = {}, number = {}, pages = {106209}, doi = {10.1016/j.neubiorev.2025.106209}, pmid = {40368261}, issn = {1873-7528}, abstract = {Demyelination, defined as the loss of myelin sheaths around neuronal axons, is increasingly recognized as a key factor in a broad range of psychiatric and neurological disorders, including schizophrenia, major depressive disorder, bipolar disorder, post-traumatic stress disorder, autism spectrum disorder, substance use disorders, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This review investigates the core mechanisms driving demyelination, its clinical impact, and emerging therapeutic strategies aimed at maintaining or restoring myelin integrity. Disruption of myelin impairs crucial neural communication pathways, resulting in cognitive, motor, and behavioral deficits that substantially reduce quality of life and create significant economic and social challenges. Key contributors to demyelination include genetic predisposition, environmental triggers, immune dysregulation, neuroinflammation, and alterations in the gut-brain axis mediated by the vagus nerve. Promising therapies include sphingosine 1-phosphate receptor modulators and muscarinic acetylcholine receptor antagonists, both of which diminish immune-related myelin damage and may enhance neuroprotection. In addition, the novel antidepressant arketamine appears to boost myelination through transforming growth factor-β1 signaling pathways. Approaches targeting the gut-brain axis, such as noninvasive transcutaneous auricular vagus nerve stimulation and fecal microbiota transplantation, may also help reduce inflammation and support myelin repair. Future research should center on clarifying the precise molecular mechanisms of demyelination, developing targeted therapies, and leveraging advanced neuroimaging for earlier detection and personalized treatment. By combining immunomodulatory and neuroprotective strategies, there is potential to significantly improve outcomes for individuals affected by demyelinating psychiatric and neurological disorders.}, }
@article {pmid40364844, year = {2025}, author = {Nazir, A and Hussain, FHN and Nadeem Hussain, TH and Al Dweik, R and Raza, A}, title = {Therapeutic targeting of the host-microbiota-immune axis: implications for precision health.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1570233}, pmid = {40364844}, issn = {1664-3224}, mesh = {Humans ; *Precision Medicine/methods ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; *Gastrointestinal Microbiome/immunology ; Animals ; *Host Microbial Interactions/immunology ; *Microbiota/immunology ; Immunomodulation ; }, abstract = {The human body functions as a complex ecosystem, hosting trillions of microbes that collectively form the microbiome, pivotal in immune system regulation. The host-microbe immunological axis maintains homeostasis and influences key physiological processes, including metabolism, epithelial integrity, and neural function. Recent advancements in microbiome-based therapeutics, including probiotics, prebiotics and fecal microbiota transplantation, offer promising strategies for immune modulation. Microbial therapies leveraging microbial metabolites and engineered bacterial consortia are emerging as novel therapeutic strategies. However, significant challenges remain, including individual microbiome variability, the complexity of host-microbe interactions, and the need for precise mechanistic insights. This review comprehensively examines the host microbiota immunological interactions, elucidating its mechanisms, therapeutic potential, and the future directions of microbiome-based immunomodulation in human health. It will also critically evaluate challenges, limitations, and future directions for microbiome-based precision medicine.}, }
@article {pmid40364435, year = {2025}, author = {Zhang, Y and Wei, Y and Han, X and Shi, L and Yu, H and Ji, X and Gao, Y and Gao, Q and Zhang, L and Duan, Y and Li, W and Yuan, Y and Shi, J and Cheng, L and Li, Y}, title = {Faecalibacterium prausnitzii prevents age-related heart failure by suppressing ferroptosis in cardiomyocytes through butyrate-mediated LCN2 regulation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2505119}, doi = {10.1080/19490976.2025.2505119}, pmid = {40364435}, issn = {1949-0984}, mesh = {Animals ; *Myocytes, Cardiac/metabolism/drug effects/microbiology ; *Ferroptosis/drug effects ; *Heart Failure/prevention &amp; control/microbiology/metabolism ; Rats ; Gastrointestinal Microbiome ; Humans ; *Butyrates/metabolism ; Fecal Microbiota Transplantation ; Male ; *Faecalibacterium prausnitzii/physiology/genetics ; *Lipocalin-2/metabolism/genetics ; Aged ; Aging ; Dysbiosis/microbiology ; Female ; Rats, Sprague-Dawley ; }, abstract = {Aging is a primary driver of the escalating prevalence of heart failure (HF). Age-associated gut microbiota dysbiosis has been implicated in various age-related diseases, yet its role in age-related HF remains largely unexplored. In this study, we sought to explore the potential link between age-related gut microbiota alterations and HF in the elderly. We analyzed a publicly available single-cell sequencing dataset, which revealed markedly increased ferroptosis activity in cardiac myocytes of elderly individuals compared to their younger counterparts. Notably, treatment with the ferroptosis inhibitor, ferrostatin-1, mitigated cardiac ferroptosis and prevented cardiac dysfunction in aging rats. Furthermore, fecal microbiota transplantation from elderly HF patients significantly increased cardiac ferroptosis activity and induced cardiac dysfunction in healthy recipient rats. Integrated 16S rRNA sequencing and PCR quantification revealed a marked depletion of Faecalibacterium prausnitzii (F. prausnitzii) in elderly individuals, with a more pronounced decline in elderly patients with HF. Oral administration of F. prausnitzii or its metabolite butyrate effectively attenuated age-related HF through inhibiting ferroptosis. Additionally, gene-editing techniques were employed to generate F. prausnitzii BCoAT mutant deficient in butyrate production. Intriguingly, the protective effect was lost in the butyrate-deficient F. prausnitzii strain. Mechanistically, butyrate reduced intracellular iron accumulation and suppressed ferroptosis by downregulating LCN2 expression in senescent cardiomyocytes. Our findings highlight the critical role of aged microbiota-induced ferroptosis in HF and propose F. prausnitzii or butyrate may serve as potential targets for the prevention and treatment of age-related HF.}, }
@article {pmid40361641, year = {2025}, author = {Mafe, AN and Büsselberg, D}, title = {Could a Mediterranean Diet Modulate Alzheimer's Disease Progression? The Role of Gut Microbiota and Metabolite Signatures in Neurodegeneration.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, doi = {10.3390/foods14091559}, pmid = {40361641}, issn = {2304-8158}, support = {NPRP 14S0311-210033//Qatar National Research Fund/ ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), the most common form of dementia, represent a growing global health crisis, yet current treatment strategies remain primarily palliative. Recent studies have shown that neurodegeneration through complex interactions within the gut-brain axis largely depends on the gut microbiota and its metabolites. This review explores the intricate molecular mechanisms linking gut microbiota dysbiosis to cognitive decline, emphasizing the impact of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, and tryptophan metabolites, on neuroinflammation, blood-brain barrier (BBB) integrity, and amyloid-β and tau pathology. The paper highlights major microbiome signatures associated with Alzheimer's disease, detailing their metabolic pathways and inflammatory crosstalk. Dietary interventions have shown promise in modulating gut microbiota composition, potentially mitigating neurodegenerative processes. This review critically examines the influence of dietary patterns, such as the Mediterranean and Western diets, on microbiota-mediated neuroprotection. Bioactive compounds like prebiotics, omega-3 fatty acids, and polyphenols exhibit neuroprotective effects by modulating gut microbiota and reducing neuroinflammation. Furthermore, it discusses emerging microbiome-based therapeutic strategies, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT), as potential interventions for slowing Alzheimer's progression. Despite these advances, several knowledge gaps remain, including interindividual variability in microbiome responses to dietary interventions and the need for large-scale, longitudinal studies. The study proposes an integrative, precision medicine approach, incorporating microbiome science into Alzheimer's treatment paradigms. Ultimately, cognizance of the gut-brain axis at a mechanistic level could unlock novel therapeutic avenues, offering a non-invasive, diet-based strategy for managing neurodegeneration and improving cognitive health.}, }
@article {pmid40361238, year = {2025}, author = {Maschek, S and Østergaard, TH and Krych, L and Zachariassen, LF and Sørensen, DB and Junker Mentzel, CM and Hansen, AK and Sjögren, JM and Barfod, KK}, title = {Investigating fecal microbiota transplants from individuals with anorexia nervosa in antibiotic-treated mice using a cross-over study design.}, journal = {Journal of eating disorders}, volume = {13}, number = {1}, pages = {82}, pmid = {40361238}, issn = {2050-2974}, abstract = {Anorexia nervosa (AN) is a complex and serious mental disorder, which may affect individuals of all ages and sex, but primarily affecting young women. The disease is characterized by a disturbed body image, restrictive eating behavior, and a lack of acknowledgment of low body weight. The underlying causes of AN remain largely unknown, and current treatment options are limited to psychotherapy and nutritional support. This paper investigates the impact of Fecal Microbiota Transplants (FMT) from patients with AN on food intake, body weight, behavior, and gut microbiota into antibiotic-treated mice. Two rounds of FMT were performed using AN and control (CO) donors. During the second round of FMT, a subset of mice received gut microbiota (GM) from a different donor type. This split-group cross-over design was chosen to demonstrate any recovery effect of FMT from a non-eating disorder state donor. The first FMT, from donors with AN, resulted in lower food intake in mice without affecting body weight. Analysis of GM showed significant differences between AN and CO mice after FMT1, before cross-over. Specific bacterial genera and families Ruminococcaceae, Lachnospiraceae, and Faecalibacterium showed different abundances in AN and CO receiving mice. Behavioral tests showed decreased locomotor activity in AN mice after FMT1. After FMT2, serum analysis revealed higher levels of appetite-influencing hormones (PYY and leptin) in mice receiving AN-GM. Overall, the results suggest that AN-GM may contribute to altered food intake and appetite regulation, which can be ameliorated with FMT from a non-eating disorder state donor potentially offering FMT as a supportive treatment for AN.}, }
@article {pmid40359452, year = {2025}, author = {Yang, G and Li, M and Zheng, X and Chen, X and Peng, Y and Li, J and Yang, S and Chen, H and Wang, Y and Zhang, H and Gong, C and Hu, F and Wan, J and Zhu, Z and Zhang, L and Li, R}, title = {Trehalose Acts as a Mediator: Imbalance in Brain Proteostasis Induced by Polystyrene Nanoplastics via Gut Microbiota Dysbiosis during Early Life.}, journal = {ACS nano}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsnano.5c01639}, pmid = {40359452}, issn = {1936-086X}, abstract = {As an emerging contaminant, nanoplastics have evolved into a global ecological issue. Studies have shown that nanoplastics induce neurotoxicity across species, however, the causal mechanism remains unknown. This study aimed to explore the mechanism underlying the neurotoxicity caused by polystyrene nanoplastics (PS-NPs) via microbiota-gut-brain axis in immature mice, which serve as a model of infants and young children who are at higher exposure risk to NPs. The results indicated that while only a minority of PS-NPs reached the brain after exposure, they still had significant neurotoxic effects, as reflected by abnormalities in behavior, biochemical marker levels and histopathology. Proteomics and quantification analyses revealed that a proteostasis imbalance mediated by lysosomal and proteasome dysfunction in the brain is the key reason for the induced neurotoxicity. Further, we confirmed the indirect role of gut microbiota in the neurotoxicity induced by PS-NPs through 16S rDNA analyses and fecal microbiota transplantation. Crucial bacterial species such as Eubacterium coprostanoligenes potentially act as indicators for gut dysbiosis after PS-NPs exposure. Notably, we first estimated the indirect effect of gut microbiota on neurotoxicity attributed to PS-NPs in immature mice as 39.20% by high-dimensional mediation analysis. Trehalose was identified as a mediator connecting the gut microbiota and the brain, and the crucial role of trehalose supplementation was highlighted in remodeling the brain proteostasis to alleviate the neurotoxicity in immature mice. These findings are expected to contribute to a deeper understanding of the risk assessment and health protection of the nervous system from exposure to PS-NPs early in life.}, }
@article {pmid40359297, year = {2025}, author = {Pakuwal, E and Tan, JL and Page, AJ and Stringer, AM and Woodman, RJ and Chinnaratha, MA}, title = {A systematic review and meta-analysis on the efficacy of fecal microbiome transplantation in patients with severe alcohol-associated hepatitis.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MEG.0000000000003003}, pmid = {40359297}, issn = {1473-5687}, abstract = {BACKGROUND: Severe alcohol-associated hepatitis (sAH) has a high short-term mortality, with limited treatment options. Fecal microbiota transplantation (FMT) has shown benefits in small, uncontrolled studies.<br><br>AIM: Perform a systematic review and meta-analysis to provide updated evidence on the efficacy and safety of FMT in sAH patients.<br><br>METHOD: Electronic databases were searched till 4 December 2023 for studies comparing FMT with standard of care (SOC) in sAH patients. Sensitivity analysis (leave-one-out method) and subgroup analyses were performed. Pooled risk ratio (RR) was used to compare the survival outcomes.<br><br>RESULTS: Eight studies with 444 patients (FMT: 218; SOC: 226) met the eligibility criteria and were included in this meta-analysis. The 28- and 90-day survival range was higher in the FMT group (75-100% and 53-87%) compared to the SOC group (48-80% and 25-56%). The random-effects model showed a statistically significant increase in survival in the FMT arm at 28 days [RR (95% confidence interval) 2.30 (1.24-4.28), P = 0.01] and 90 days [2.53 (1.34-4.77), P < 0.001]. However, there was no statistically significant change in survival at the 6-month [1.89 (0.89-4.05), P = 0.10] and the 12-month time [1.86 (0.68-5.08), P = 0.23]. Sensitivity analysis showed no major changes in the overall effect sizes, and subgroup analysis showed that the survival benefit was restricted only to the retrospective studies. No serious treatment-related adverse events were reported.<br><br>CONCLUSION: FMT is a safe and efficacious treatment option that improves short-term survival in sAH patients, without major adverse events. A multicentre randomized controlled trial with an adequate sample size is required to confirm these findings.}, }
@article {pmid40357397, year = {2025}, author = {Xing, G and Cui, Y and Guo, Z and Han, B and Zhao, G}, title = {Progress on the mechanism of intestinal microbiota against colorectal cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1565103}, pmid = {40357397}, issn = {2235-2988}, mesh = {*Colorectal Neoplasms/therapy/microbiology/prevention &amp; control/immunology ; Humans ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Immunotherapy ; Signal Transduction ; }, abstract = {The intestinal microbiota plays a crucial role in the occurrence and development of colorectal cancer, and its anti - colorectal cancer mechanism has become a research hotspot. This article comprehensively expounds on the molecular mechanisms of the intestinal microbiota in anti - colorectal cancer, including aspects such as immune regulation, activation of carcinogenic signaling pathways (it should be noted that it is more reasonable to be "inhibition of carcinogenic signaling pathways"), metabolite - mediated effects, and maintenance of intestinal barrier function. At the same time, it explores the roles and potential mechanisms of intervention methods such as probiotic supplementation therapy, immunotherapy, and fecal microbiota transplantation. In addition, it analyzes the impact of the intestinal flora on the therapeutic efficacy of colorectal cancer. The existing research results are summarized, and the future research directions are prospected, with the aim of providing new theoretical bases and treatment ideas for the prevention and treatment of colorectal cancer.}, }
@article {pmid40108157, year = {2025}, author = {Huang, R and Shen, ZY and Huang, D and Zhao, SH and Dan, LX and Wu, P and Tang, QZ and Ma, ZG}, title = {Microbiota-indole-3-propionic acid-heart axis mediates the protection of leflunomide against αPD1-induced cardiotoxicity in mice.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2651}, pmid = {40108157}, issn = {2041-1723}, support = {82070410; 82270248//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Leflunomide/pharmacology/therapeutic use ; Mice ; *Cardiotoxicity/prevention &amp; control/etiology/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Indoles/pharmacology/metabolism ; Myocytes, Cardiac/drug effects/metabolism ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; Mice, Inbred C57BL ; *Heart/drug effects ; *Propionates/metabolism/pharmacology ; Male ; Receptors, Aryl Hydrocarbon/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/adverse effects ; }, abstract = {Anti-programmed death 1 (αPD1) immune checkpoint blockade is used in combination for cancer treatment but associated with cardiovascular toxicity. Leflunomide (Lef) can suppress the growth of several tumor and mitigate cardiac remodeling in mice. However, the role of Lef in αPD1-induced cardiotoxicity remains unclear. Here, we report that Lef treatment inhibits αPD1-related cardiotoxicity without compromising the efficacy of αPD1-mediated immunotherapy. Lef changes community structure of gut microbiota in αPD1-treated melanoma-bearing mice. Moreover, mice receiving microbiota transplants from Lef+αPD1-treated melanoma-bearing mice have better cardiac function compared to mice receiving transplants from αPD1-treated mice. Mechanistically, we analyze metabolomics and identify indole-3-propionic acid (IPA), which protects cardiac dysfunction in αPD1-treated mice. IPA can directly bind to the aryl hydrocarbon receptor and promote phosphoinositide 3-kinase expression, thus curtailing the cardiomyocyte response to immune injury. Our findings reveal that Lef mitigates αPD1-induced cardiac toxicity in melanoma-bearing mice through modulation of the microbiota-IPA-heart axis.}, }
@article {pmid40356099, year = {2025}, author = {Zhang, Y and Ni, P and Chen, H and Tang, L and Song, H and Wen, H and Miao, Y and Li, W and Li, X}, title = {Vitamin D3 ameliorates hyperglycemia by modulating gut microbiota and metabolites in prediabetic KKay mice.}, journal = {Food research international (Ottawa, Ont.)}, volume = {211}, number = {}, pages = {116369}, doi = {10.1016/j.foodres.2025.116369}, pmid = {40356099}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Prediabetic State/metabolism/drug therapy/microbiology ; *Hyperglycemia/drug therapy/metabolism ; *Cholecalciferol/pharmacology ; Male ; Blood Glucose/metabolism/drug effects ; Diet, High-Fat/adverse effects ; Toll-Like Receptor 4/metabolism ; Glucose Tolerance Test ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Feces/microbiology ; Proto-Oncogene Proteins c-akt/metabolism ; }, abstract = {Prediabetes represents a pivotal stage in the development and pathogenesis of diabetes, during which notable alterations in the gut microbiota can be observed. Vitamin D (VD) showed anti-diabetic properties, but it is unknown whether the improvement of VD on hyperglycemia is associated with gut microbiota. Thus, our objective was to investigate and verify the effects of VD3 on glucose metabolism in prediabetes, as well as to elucidate the underlying mechanisms. In this study, different concentrations of VD3 were intraperitoneally administered to prediabetic mice induced by high fat diet for 16 weeks. Biochemical analyses, oral glucose tolerance test, 16S rRNA and untargeted metabolomics were used, the mechanism was explored. Then, fecal suspensions collected from the above donors were transplanted into KKay mice for 6 weeks, and the relevant indicators were measured. The results showed that VD3 intervention alleviated glucose metabolism in KKay mice. It increased the protein expression of colon tight junction proteins, alleviated metabolic endotoxemia and inflammation, so that reduced tumor necrosis factor alpha (TNFα) induced toll-like receptor 4/nuclear factor kappa-B (TLR4/NFκB) and improvement of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) insulin signaling pathway. VD3 affected the structure of gut microbiota and metabolites, and functional prediction analysis suggested that VD3 may affect carbohydrate. Besides, the effect of VD3 could be delivered by fecal microbiota transplantation (FMT). Consequently, VD3 ameliorate glucose metabolism by modulating gut microbiota and metabolites in KKay mice, and this ability could be transferred by FMT.}, }
@article {pmid40355758, year = {2025}, author = {Saeedi Saravi, SS and Pugin, B and Constancias, F and Shabanian, K and Spalinger, M and Thomas, A and Le Gludic, S and Shabanian, T and Karsai, G and Colucci, M and Menni, C and Attaye, I and Zhang, X and Allemann, MS and Lee, P and Visconti, A and Falchi, M and Alimonti, A and Ruschitzka, F and Paneni, F and Beer, JH}, title = {Gut microbiota-dependent increase in phenylacetic acid induces endothelial cell senescence during aging.}, journal = {Nature aging}, volume = {}, number = {}, pages = {}, pmid = {40355758}, issn = {2662-8465}, support = {#310030_21A053//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; #CRSK-3_229134//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; #21A053//Novartis Stiftung f&#xfc;r Medizinisch-Biologische Forschung (Novartis Foundation for Medical-Biological Research)/ ; }, abstract = {Endothelial cell senescence is a key driver of cardiovascular aging, yet little is known about the mechanisms by which it is induced in vivo. Here we show that the gut bacterial metabolite phenylacetic acid (PAA) and its byproduct, phenylacetylglutamine (PAGln), are elevated in aged humans and mice. Metagenomic analyses reveal an age-related increase in PAA-producing microbial pathways, positively linked to the bacterium Clostridium sp. ASF356 (Clos). We demonstrate that colonization of young mice with Clos increases blood PAA levels and induces endothelial senescence and angiogenic incompetence. Mechanistically, we find that PAA triggers senescence through mitochondrial H2O2 production, exacerbating the senescence-associated secretory phenotype. By contrast, we demonstrate that fecal acetate levels are reduced with age, compromising its function as a Sirt1-dependent senomorphic, regulating proinflammatory secretion and redox homeostasis. These findings define PAA as a mediator of gut-vascular crosstalk in aging and identify sodium acetate as a potential microbiome-based senotherapy to promote healthy aging.}, }
@article {pmid40354906, year = {2025}, author = {Zain, NMM and Merrick, B and Martin-Lilley, T and Edwards, LA and Ter Linden, D and Tsoka, S and Mason, AJ and Hatton, GB and Allen, E and Royall, PG and Lilley, AK and Bruce, KD and Shawcross, DL and Goldenberg, SD and Forbes, B}, title = {Bacterial diversity, viability and stability in lyophilised faecal microbiota capsules support ongoing clinical use.}, journal = {International journal of pharmaceutics}, volume = {}, number = {}, pages = {125703}, doi = {10.1016/j.ijpharm.2025.125703}, pmid = {40354906}, issn = {1873-3476}, abstract = {Lyophilised encapsulated faecal microbiota provides a practical and cost-effective treatment option to patients with recurrent Clostridioides difficile infection. This study focused on quality assurance of an enteric-coated capsule formulation of FMT as a medicinal product by evaluating bacterial composition, diversity and viability through manufacturing steps and upon product storage at a range of temperatures. Faecal donations from pre-screened healthy individuals (n = 5) were processed according to a published protocol into one or more treatments; 5 capsules = 1 treatment dose/patient. Culture-independent next-generation 16S rRNA gene sequencing was used to speciate and quantify bacteria using a live-dead cell separation method to discriminate the viable cell load. Species diversity in donor stools aligned with other healthy gut microbiome and remained unchanged through the manufacturing process and after storage at -80 °C for 36 weeks. While diversity indices were consistent, a notable difference was observed between viable and total microbiome, particularly in species richness, which decreased when non-viable or compromised cells were excluded from analysis. Anaerobic species exhibited minimal viability loss despite processing in an aerobic environment. Furthermore, capsules were stable with storage at -20 °C and 2-8 °C, with no significant reduction of total live bacterial load after 24 weeks. In summary, 'live-dead' culture-independent analysis was used to characterise the viable faecal microbiome, which retained a diversity of bacterial species, including anaerobes, through manufacture and after storage in capsules for up to 36 weeks. These data support the comparable effectiveness of lyophilised encapsulated FMT to other formulations and delivery methods.}, }
@article {pmid40354842, year = {2025}, author = {Zhang, S and Mao, X and Chang, L and Li, M and Wei, C and Li, H and Shen, X and Niu, K and Zhang, R and Jiang, Y and Lu, X and Song, Y and Zhou, L and Gao, L and Zhao, Z and Niu, L and Yang, Q and Hou, Y and Wu, Y}, title = {Bazi Bushen Capsule Modulates Akkermansia muciniphila and Spermidine Metabolism to Attenuate Brain Aging in SAMP8 Mice.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {119944}, doi = {10.1016/j.jep.2025.119944}, pmid = {40354842}, issn = {1872-7573}, abstract = {Bazi Bushen Capsule (BZBS), a traditional Chinese medicine formulation composed of multiple bioactive herbal components, has been validated in multicenter randomized double-blind controlled trials for its potent anti-aging properties. Previous studies from our group have demonstrated that BZBS effectively restores gut microbiota homeostasis and attenuates the impairment of intestinal barrier function, thereby ameliorating age-related cognitive decline. However, the specific molecular mechanisms by which BZBS modulates key microbial-metabolite networks to delay brain aging remain poorly understood and warrant further investigation.<br><br>AIM OF THE STUDY: This study aims to elucidate the key microbiota-metabolite networks through which BZBS improves cognitive function and delays brain aging in senescence-accelerated mouse-prone 8 (SAMP8) mice.<br><br>MATERIALS AND METHODS: Eight-week-old male SAMP8 mice were used as experimental models, randomly divided into Model, BZ-low (0.5 g/kg/d BZBS), BZ-high (1 g/kg/d BZBS), and RAPA (2 mg/kg/d rapamycin) groups. Senescence-accelerated mouse resistant 1 (SAMR1) mice served as the control group. Cognitive function was assessed using the Barnes Maze test and the three-chamber social test. The structural damage and pathological changes in the brain tissue were evaluated through transcranial Doppler, micro-computed tomography, Nissl staining, and Western blot analysis. Next, the intestinal barrier function was detected by hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and immunofluorescence (IF) staining. Characteristic bacteria were identified by 16S rRNA sequencing, and metabolomic profiling was performed using non-targeted metabolomics. Akkermansia muciniphila (Akk) was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate its contribution to intestinal barrier function.<br><br>RESULTS: The study revealed that BZBS therapy not only enhances cognitive capabilities but also restores the intestinal barrier function. Akk was identified as a key regulatory agent mediating the therapeutic effects of BZBS. BZBS administration significantly increased the abundance of Akk and modulated its metabolite profile, particularly components associated with spermidine, thereby reinforcing the intestinal barrier and mitigating age-related cognitive decline. Furthermore, this study demonstrated that Akk, administered via fecal microbiota transplantation, alleviated dextran sulfate sodium (DSS)-induced colitis..<br><br>CONCLUSION: The results showed that BZBS capsule, a traditional Chinese medicine, may delay brain aging in SAMP8 mice by modulating Akk and its spermidine production.}, }
@article {pmid40354071, year = {2025}, author = {Fernandez, E and Wargo, JA and Helmink, BA}, title = {The Microbiome and Cancer: A Translational Science Review.}, journal = {JAMA}, volume = {}, number = {}, pages = {}, doi = {10.1001/jama.2025.2191}, pmid = {40354071}, issn = {1538-3598}, abstract = {IMPORTANCE: Growing evidence suggests that microbes located within the gastrointestinal tract and other anatomical locations influence the development and progression of diseases such as cancer.<br><br>OBSERVATIONS: Clinical and preclinical evidence suggests that microbes in the gastrointestinal tract and other anatomical locations, such as the respiratory tract, may affect carcinogenesis, development of metastases, cancer treatment response, and cancer treatment-related adverse effects. Within tumors of patients with cancer, microbes may affect response to treatment, and therapies that reduce or eliminate these microbes may improve outcomes in patients with cancer. Modulating gastrointestinal tract (gut) microbes through fecal microbiota transplant and other strategies such as dietary intervention (eg, high-fiber diet intervention) has improved outcomes in small studies of patients treated with cancer immunotherapy. In contrast, disruption of the gut microbiota by receipt of broad-spectrum antibiotics prior to treatment with cancer immunotherapy has been associated with poorer overall survival and higher rates of adverse effects in patients treated with immune checkpoint blockade for solid tumors and also with chimeric antigen receptor T-cell therapy for hematologic malignancies.<br><br>CONCLUSIONS AND RELEVANCE: Microbes in the gut and other locations in the body may influence the development and progression of cancer and may affect the response to adverse effects from cancer therapy. Future therapies targeting microbes in the gut and other locations in the body could potentially improve outcomes in patients with cancer.}, }
@article {pmid40352262, year = {2025}, author = {Bao, M and Wu, R and Li, J and Tang, R and Song, C}, title = {Research summary, possible mechanisms and perspectives of gut microbiota changes causing precocious puberty.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1596654}, doi = {10.3389/fnut.2025.1596654}, pmid = {40352262}, issn = {2296-861X}, abstract = {The increasing global incidence of precocious puberty, linked to environmental, metabolic, and genetic factors, necessitates innovative therapies beyond gonadotropin-releasing hormone (GnRH) analogs. Accumulating evidence implicates gut microbiota dysbiosis as a pivotal regulator of pubertal timing via interactions with hormone metabolism (e.g., estrogen reactivation via β-glucuronidase), neuroendocrine pathways (nitric oxide signaling), and immune-inflammatory responses. This review delineates taxonomic alterations in central precocious puberty (CPP) and obesity-related subtypes, including Streptococcus enrichment and Alistipes depletion, alongside functional shifts in microbial metabolite production. Mechanistic insights highlight microbiota-driven modulation of the hypothalamic-pituitary-gonadal (HPG) axis, leptin/insulin dynamics, and epigenetic regulation. Emerging interventions-probiotics, fecal microbiota transplantation (FMT), and dietary modifications-demonstrate efficacy in preclinical models and early clinical studies for delaying puberty onset and restoring hormonal balance. Translational efforts to validate these strategies are critical for addressing the clinical and psychosocial challenges posed by precocious puberty, positioning gut microbiota modulation as a novel therapeutic frontier in pediatric endocrinology.}, }
@article {pmid40350912, year = {2025}, author = {Lu, CY and Yuan, XM and He, LH and Mao, JR and Chen, YG}, title = {[Mechanism of total flavone of Abelmoschus manihot in treating ulcerative colitis and depression via intestinal flora-glycerophospholipid metabolism- macrophage polarization pathway].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {50}, number = {5}, pages = {1286-1297}, doi = {10.19540/j.cnki.cjcmm.20241111.701}, pmid = {40350912}, issn = {1001-5302}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Abelmoschus/chemistry ; *Macrophages/drug effects/immunology/metabolism ; *Colitis, Ulcerative/drug therapy/metabolism/microbiology/genetics/immunology ; *Flavones/administration &amp; dosage ; Male ; *Depression/drug therapy/metabolism/microbiology/genetics ; *Glycerophospholipids/metabolism ; Humans ; *Drugs, Chinese Herbal/administration &amp; dosage ; Mice, Inbred C57BL ; }, abstract = {This study delves into the mechanism of total flavone of Abelmoschus manihot(TFA) in treating ulcerative colitis(UC) and depression via inhibiting M1 polarization of macrophages and reshaping intestinal flora and glycerolphospholipid metabolism. The study established a mouse model of UC and depression induced by chronic restraint stress(CRS) and dextran sulfate sodium(DSS). The fecal microbiota transplantation(FMT) experiment after TFA intervention was conducted. Mice in the FMT donor group were modeled and treated, and fecal samples were taken to prepare the bacterial solution. Mice in the FMT receptor group were treated with antibiotic intervention, and then administered bacterial solution by gavage from mice in the donor group, followed by UC depression modeling. After the experiment, behavioral tests were conducted to evaluate depressive-like behaviors by measuring the levels of 5-hydroxytryptamine(5-HT) and brain-derived neurotrophic factor(BDNF) in the hippocampus of mice. The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the brain and colon tissue of mice were also measured, and the polarization status of macrophages was evaluated by measuring the mRNA levels of CD86 and CD206. 16S ribosomal RNA(16S rRNA) sequencing technology was used to analyze changes in the intestinal flora of mice. Wide target lipidomics was used to detect serum lipid metabolite levels in mice after FMT,and correlation analysis was conducted between lipids and differential intestinal flora significantly regulated by TFA. In vitro experiments, representative glycerophospholipid metabolites and glycerophospholipid inhibitors were used to intervene in Raw264.7 macrophages, and the mRNA levels of TNF-α,IL-6,IL-1β,CD86,and CD206 were detected. The results showed that TFA and FMT after intervention could significantly improve depressive-like behavior and intestinal inflammation in mice with UC and depression, significantly downregulate pro-inflammatory cytokines and CD86 mRNA expression in brain and colon tissue, inhibiting M1 polarization of macrophages, and significantly upregulate CD206 mRNA expression, promoting M2 polarization of macrophages. In addition, the high-dose group had a more significant effect. After TFA intervention, FMT significantly corrected the metabolic disorder of glycerophospholipids in mice with UC and depression, and there was a significant correlation between differential intestinal flora and glycerophospholipids. In vitro experiments showed that glycerophospholipid metabolites, especially lysophosphatidylcholine(LPC),significantly upregulated pro-inflammatory cytokines and CD86 mRNA expression, promote M1 polarization of macrophages, while glycerophospholipid inhibitors had the opposite effect. The results indicate that TFA effectively treats depression and UC by correcting intestinal flora dysbiosis and reshaping glycerophospholipid metabolism, thereby inhibiting M1 polarization of macrophages.}, }
@article {pmid40350437, year = {2025}, author = {Hsu, CY and Ahmad, I and Maya, RW and Abass, MA and Gupta, J and Singh, A and Joshi, KK and Premkumar, J and Sahoo, S and Khosravi, M}, title = {The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {530}, pmid = {40350437}, issn = {1479-5876}, mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy/microbiology/physiopathology ; *Gastrointestinal Microbiome ; Dysbiosis ; }, abstract = {BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in its pathophysiology. The main objective of this review was to synthesize qualitative and quantitative data from research examining the gut microbiota composition, inflammatory markers, and therapeutic outcomes of interventions targeting the microbiome in the context of ME/CFS.<br><br>METHODS: The data collection involved a detailed search of peer-reviewed English literature from January 1995 to January 2025, focusing on studies related to the microbiome and ME/CFS. This comprehensive search utilized databases such as PubMed, Scopus, and Web of Science, with keywords including "ME/CFS," "Gut-Brain Axis," "Gut Health," "Intestinal Dysbiosis," "Microbiome Dysbiosis," "Pathophysiology," and "Therapeutic Approaches." Where possible, insights from clinical trials and observational studies were included to enrich the findings. A narrative synthesis method was also employed to effectively organize and present these findings.<br><br>RESULTS: The study found notable changes in the gut microbiota diversity and composition in ME/CFS patients, contributing to systemic inflammation and worsening cognitive and physical impairments. As a result, various microbiome interventions like probiotics, prebiotics, specific diets, supplements, fecal microbiota transplantation, pharmacological interventions, improved sleep, and moderate exercise training are potential therapeutic strategies that merit further exploration.<br><br>CONCLUSIONS: Interventions focusing on the gut-brain axis may help reduce neuropsychiatric symptoms in ME/CFS by utilizing the benefits of the microbiome. Therefore, identifying beneficial microbiome elements and incorporating their assessments into clinical practice can enhance patient care through personalized treatments. Due to the complexity of ME/CFS, which involves genetic, environmental, and microbial factors, a multidisciplinary approach is also necessary. Since current research lacks comprehensive insights into how gut health might aid ME/CFS treatment, standardized diagnostics and longitudinal studies could foster innovative therapies, potentially improving quality of life and symptom management for those affected.}, }
@article {pmid40350306, year = {2025}, author = {Liu, C and Gao, Y and Chen, Y and Zhu, L and Rao, F and Huang, Y and Zeng, Y and Cai, R and Wang, F and Cheng, J}, title = {Nephropathy II Decoction Attenuates Renal Fibrosis via Regulating TLR4 and Gut Microbiota Along the Gut-Kidney Axis.}, journal = {Biological &amp; pharmaceutical bulletin}, volume = {48}, number = {5}, pages = {577-594}, doi = {10.1248/bpb.b24-00863}, pmid = {40350306}, issn = {1347-5215}, mesh = {Animals ; *Toll-Like Receptor 4/metabolism/genetics ; *Gastrointestinal Microbiome/drug effects ; Fibrosis ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Kidney/pathology/drug effects/metabolism ; Male ; Myeloid Differentiation Factor 88/metabolism ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury/drug therapy/pathology/metabolism ; Signal Transduction/drug effects ; NF-kappa B/metabolism ; }, abstract = {Nephropathy II Decoction (NED) is a widely used Chinese medicinal formulation for managing chronic kidney disease (CKD). Despite its extensive application, the precise mechanisms underlying its therapeutic effects remain poorly understood. This study aims to elucidate the role of NED in attenuating renal fibrosis and to explore its impact on the gut-kidney axis. The principal constituents of NED were analyzed using ultra-performance LC-tandem mass spectrometry (UPLC-MS/MS). A bilateral renal ischemia-reperfusion injury (bIRI) model was employed to induce fibrosis. RT-qPCR was utilized to assess the expression of mRNA related to the toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) and nuclear factor-κB (NF-κB) signaling pathway. Western blotting analysis was performed to identify changes in renal fibrosis markers, TLR4/MyD88/NF-κB pathway proteins, and the colon proteins ZO-1 and Occludin-1. Serum levels of uremic toxins were quantified using enzyme-linked immunosorbent assay (ELISA), and 16S ribosomal RNA (rRNA) gene sequencing was conducted to explore changes in the gut microbiome of the mice. Our study demonstrated that mice in the NED group exhibited reduced serum creatinine, blood urea nitrogen, and urinary protein levels, alongside improvements in kidney damage and a decrease in renal fibrosis markers. In the bIRI group, TLR4/MyD88/NF-κB protein and mRNA levels, as well as intestinal tight junction proteins and enterogenic uremic toxins, were significantly reduced. NED treatment reversed these changes and modified the gut microbiota. Furthermore, fecal microbial transplantation (FMT) alleviated kidney damage and fibrosis in bIRI mice. In summary, NED ameliorates kidney injury and fibrosis by modulating the gut microbiota and may further attenuate fibrosis through the inhibition of TLR4 expression, thereby influencing the gut-kidney axis.}, }
@article {pmid40350047, year = {2025}, author = {Huang, H and Yang, C and Li, S and Zhan, H and Tan, J and Chen, C and Liu, J and Wang, M and Li, H}, title = {Lizhong decoction alleviates experimental ulcerative colitis via regulating gut microbiota-SCFAs-Th17/Treg axis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {119958}, doi = {10.1016/j.jep.2025.119958}, pmid = {40350047}, issn = {1872-7573}, abstract = {Lizhong decoction (LZD), a Traditional Chinese Medicine formula, is widely utilized to treat gastrointestinal diseases, including ulcerative colitis in China for thousands of years.<br><br>AIM OF THE STUDY: To investigate whether the protective effect of LZD on ulcerative colitis is dependent on gut microbiota and T-cell immune homeostasis.<br><br>MATERIAL AND METHODS: The preventive effects of LZD on dextran sodium sulfate (DSS)-induced colitis mice were evaluated through the measurement of body weight, disease activity index, colon length and hematoxylin-eosin staining. Flow cytometry was used to detect the ratio of Th17/Treg cells. Pseudo sterile mice and fecal transplantation experiments were used to investigate whether the preventive effect of LZD was dependent on the gut microbiota. The alterations of gut microbiota were identified by the 16S rDNA sequencing. The content of intestinal short-chain fatty acids (SCFAs) was detected by LC-MS/MS analysis. The downstream signal pathways of SCFAs were detected by the immunoblotting.<br><br>RESULTS: LZD administration significantly alleviated weight loss and intestinal injury in DSS-induced colitis mice. LZD administration also promotes the balance of Th17/Treg cells. Moreover, LZD administration relies on gut microbiota to alleviate ulcerative colitis and regulate Th17/Treg cell balance. LZD administration significantly improves gut microbial composition in colitis mice, elevating the abundance of SCFAs producing bacterium such as lachnospiraceae_nk4a136_group and Akkermansia. LZD treatment further increases the abundance of SCFAs and promotes activation of free fatty acid activated receptor 2 (FFAR2).<br><br>CONCLUSION: LZD administration promotes Th17/Treg cell balance in a gut microbiota-SCFAs dependent manner, which in turn ameliorates ulcerative colitis.}, }
@article {pmid40350003, year = {2025}, author = {Nohesara, S and Mostafavi-Abdolmaleky, H and Dickerson, F and Pinto-Tomas, AA and Jeste, DV and Thiagalingam, S}, title = {Associations of Microbiome Pathophysiology with Social Activity and Behavior are Mediated by Epigenetic Modulations: Avenues for Designing Innovative Therapeutic Strategies.}, journal = {Neuroscience and biobehavioral reviews}, volume = {}, number = {}, pages = {106208}, doi = {10.1016/j.neubiorev.2025.106208}, pmid = {40350003}, issn = {1873-7528}, abstract = {A number of investigations have shown that gut microbiome influences humans' ability to communicate with others, and impairments in social interactions are linked to alterations in gut microbiome composition and diversity, via epigenetic mechanisms. This article reviews the links among gut microbiome, social behavior, and epigenetic shifts relevant to gut microbiome-derived metabolites. First, we discuss how different social determinants of health, such as socioeconomic status, diet, environmental chemicals, migration, ecological conditions, and seasonal changes may influence gut microbiome composition, diversity, and functionality, along with epigenetic alterations and thereby affect social behavior. Next, we consider how gut microbiome-derived metabolites, diet, probiotics, and fecal microbiome transplantation may reduce impairments in social interactions through the adjustment of epigenetic aberrations (e.g., DNA methylation, histone modifications, and microRNAs expression) which may suppress or increase gene expression patterns. Finally, we present the potential benefits and unresolved challenges with the use of gut microbiome-targeted therapeutics in reducing social deficits.}, }
@article {pmid40349812, year = {2025}, author = {Quan, T and Zhang, W and Shi, Y and Gao, T}, title = {Melatonin-mediated intestinal microbiota homeostasis improves skin barrier damage involvement of gut-skin axis dysfunction in aging mice.}, journal = {Cellular signalling}, volume = {}, number = {}, pages = {111859}, doi = {10.1016/j.cellsig.2025.111859}, pmid = {40349812}, issn = {1873-3913}, abstract = {Researches suggested a close connection between the gut microbiome homeostasis and skin health. Melatonin, as a multifunctional molecule, has the potential to regulate intestinal homeostasis and skin function. The study further explored the potential mechanism of melatonin in ameliorating skin barrier damage from the perspective of the association between intestinal microbiota and gut-skin axis in aging mice. We established a natural aging-induced skin barrier damage mouse model with or without melatonin supplementation and fecal microbiota transplantation (FMT) to clarify the crucial role of intestinal microbiota-mediated gut-skin axis in melatonin improving skin barrier damage. Furthermore, lipopolysaccharide (LPS)-treated mice and human keratinocytes cells (HaCaT) explored the modulation mechanism of melatonin. Our results suggested that aging induced skin barrier damage, including skin microbiota disorder and epidermal barrier structure disruption, and intestinal dysbiosis. Similarly, FMT from aging mice and LPS treatment rebuild the aging-like skin barrier damage. Whereas, melatonin or resatorvid (TAK242, the antagonist of LPS) supplementation restored all consequence in aging and LPS-treated mice. In vitro, melatonin restored LPS-induced skin barrier proteins deficiency in HaCaT via decreasing the expression level of TLR4 and MyD88 and increasing the content of p-ERK, p-GSK-3β and β-catenin proteins, while the improving effects was mimicked by pretreatment with a TLR4 antagonist but were blocked by GSK-3β agonists. Our study revealed that melatonin-mediated intestinal microbiota homeostasis suppresses LPS escape to restore the skin barrier function, including skin dysbiosis and epidermal structural disruption via LPS/TLR4/MyD88/ERK/GSK-3β/β-catenin loop, further improving skin aging in mice.}, }
@article {pmid40349163, year = {2025}, author = {Huang, M and Huang, M and Liu, L and Yang, F and He, C and Sun, YC and Jiao, YR and Tang, X and Hou, J and Chen, KX and He, WZ and Wei, J and Chen, HL and Li, X and Zeng, C and Lei, GH and Li, CJ}, title = {Gut Microbiota Modulates Obesity-Associated Skeletal Deterioration Through Macrophage Aging and Grancalcin Secretion.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2502634}, doi = {10.1002/advs.202502634}, pmid = {40349163}, issn = {2198-3844}, support = {2022YFC3601900//National Key Research and Development Program of China/ ; 2022YFC2009604//National Key Research and Development Program of China/ ; 82472521//National Natural Science Foundation of China/ ; 82272560//National Natural Science Foundation of China/ ; 82261160397//National Natural Science Foundation of China/ ; 81922017//National Natural Science Foundation of China/ ; 2023QYJC011//Central South University Research Program of Advanced Interdisciplinary Studies/ ; 2022SK2023//Key Research and Development Program of Hunan Province/ ; 2023RC1027//Science and Technology Innovation Program of Hunan Province/ ; 2022RC1009//Science and Technology Innovation Program of Hunan Province/ ; 2022RC3075//Science and Technology Innovation Program of Hunan Province/ ; 2024JC0004//Major Basic Research Projects in Hunan Province/ ; 2024M763722//China Postdoctoral Science Foundation/ ; 2023JJ30896//Natural Science Foundation of Hunan/ ; 2023JJ40965//Natural Science Foundation of Hunan/ ; 2025JJ60562//Natural Science Foundation of Hunan/ ; }, abstract = {Obesity is associated with skeletal deterioration and increased fracture risk, but the underlying mechanism is unclear. Herein, it is shown that obese gut microbiota promotes skeletal deterioration by inducing bone marrow macrophages (BMMs) senescence and grancalcin (GCA) secretion. Obese mice and those receiving obese fecal microbiota transplants exhibit increased senescent macrophages and elevated GCA expression in the bone marrow. In a study of 40 participants, it is found that obese patients are associated with higher serum GCA levels. It is further revealed that obese gut-microbiota derived lipopolysaccharides (LPS) stimulate GCA expression in senescent BMMs via activating Toll-like receptor 4 pathway. Mice with depletion of the Gca gene are resistant to the negative effects of obesity and LPS on bone. Moreover, neutralizing antibody against GCA mitigates skeletal deterioration in obese mice and LPS-induced chronic inflammation mouse model. The data suggest that the interaction between gut microbiota and the immune system contributes to obesity-associated skeletal deterioration, and targeting senescent macrophages and GCA shows potential of protecting skeletal health in obese population.}, }
@article {pmid40348497, year = {2025}, author = {Munk Lauridsen, M and Jonasson, E and Bajaj, JS}, title = {Microbial Approaches to Treat and Prevent Hepatic Encephalopathy.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {2}, pages = {429-451}, doi = {10.1016/j.gtc.2024.12.006}, pmid = {40348497}, issn = {1558-1942}, mesh = {Humans ; *Hepatic Encephalopathy/prevention &amp; control/therapy/microbiology ; *Gastrointestinal Microbiome ; Probiotics/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Rifaximin/therapeutic use ; Lactulose/therapeutic use ; Gastrointestinal Agents/therapeutic use ; }, abstract = {This review articulates the significance of the gut-liver-brain axis in understanding hepatic encephalopathy (HE), emphasizing the role of gut microbiota in influencing liver and brain health. Key treatments like lactulose, rifaximin, probiotics, and fecal microbiota transplantation are examined for their ability to modulate the gut microbiome, thereby mitigating HE symptoms through reduced neurotoxin production and enhanced gut barrier integrity. The synopsis highlights both established and emerging microbial therapies, presenting them as crucial to the management and future strategies of HE. This comprehensive overview explores current therapeutic approaches alongside promising future interventions, suggesting that personalized microbiome-focused treatments may revolutionize HE management.}, }
@article {pmid40348491, year = {2025}, author = {Sartor, RB}, title = {Beyond Random Fecal Microbial Transplants: Next Generation Personalized Approaches to Normalize Dysbiotic Microbiota for Treating IBD.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {2}, pages = {333-350}, doi = {10.1016/j.gtc.2024.11.002}, pmid = {40348491}, issn = {1558-1942}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Precision Medicine/methods ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy/microbiology ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Colitis, Ulcerative/therapy/microbiology ; Crohn Disease/therapy/microbiology ; Clostridioides difficile ; Pouchitis/therapy/microbiology ; }, abstract = {This review and commentary outline the strong rationale for normalizing the abnormal microbiota of patients with ulcerative colitis, Crohn's disease, and pouchitis and focus on strategies to improve current variable outcomes of fecal microbial transplant (FMT) in ulcerative colitis. Applying lessons from successful FMT therapy of recurrent Clostridioides difficile and insights from basic scientific understanding of host/microbial interactions provide strategies to enhance clinical outcomes in IBD. We outline promising approaches to develop novel-defined consortia of live biotherapeutic products and combination treatments to improve current results and to optimize and personalize treatment approaches in individual patients and disease subsets.}, }
@article {pmid40348489, year = {2025}, author = {Silveira, MAD and Rodrigues, RR and Trinchieri, G}, title = {Intestinal Microbiome Modulation of Therapeutic Efficacy of Cancer Immunotherapy.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {2}, pages = {295-315}, doi = {10.1016/j.gtc.2024.10.005}, pmid = {40348489}, issn = {1558-1942}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology/microbiology ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {Bacteria are associated with certain cancers and may induce genetic instability and cancer progression. The gut microbiome modulates the response to cancer therapy. Training machine learning models with response associated taxa or bacterial genes predict patients' response to immunotherapies with moderate accuracy. Clinical trials targeting the gut microbiome to improve immunotherapy efficacy have been conducted. While single bacterial strains or small consortia have not be reported yet to be successful, encouraging results have been reported in small single arm and randomized studies using transplant of fecal microbiome from cancer patients who successfully responded to therapy or from healthy volunteers.}, }
@article {pmid40348488, year = {2025}, author = {Magier, SJ and Morley, TS and Kelly, CR}, title = {Optimizing Therapeutic Potential of Fecal Transplant in Inflammatory Bowel Disease.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {2}, pages = {277-293}, doi = {10.1016/j.gtc.2024.12.002}, pmid = {40348488}, issn = {1558-1942}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Colitis, Ulcerative/therapy/microbiology ; *Crohn Disease/therapy/microbiology ; Pouchitis/therapy ; Remission Induction ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract influenced by genetic, environmental, immune, and microbial factors. Reduced gut microbial diversity and elevated proinflammatory bacteria levels in IBD disrupt mucosal immunity, barrier function, and inflammatory pathways. Fecal microbiota transplantation (FMT) is a potential therapy to restore microbial balance. Studies suggest that FMT may induce remission in mild-to-moderate ulcerative colitis but show limited efficacy in Crohn's disease and pouchitis. Donor microbiota colonization correlates with remission, but varied study designs challenge findings. Further research is required to standardize FMT protocols, optimize donor selection, and ensure long-term safety.}, }
@article {pmid40348487, year = {2025}, author = {Ressler, AM and Rao, K and Young, VB}, title = {Current Approaches to Treat and Prevent Recurrence of Clostridioides difficile.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {2}, pages = {259-275}, doi = {10.1016/j.gtc.2025.02.005}, pmid = {40348487}, issn = {1558-1942}, mesh = {Humans ; *Clostridium Infections/prevention &amp; control/therapy/microbiology/drug therapy ; *Anti-Bacterial Agents/therapeutic use/adverse effects ; *Clostridioides difficile ; *Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation ; Recurrence ; Secondary Prevention/methods ; Probiotics/therapeutic use ; }, abstract = {Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) are significant causes of morbidity and mortality. The microbiome plays a significant role in the body's defense against CDI and rCDI. Antibiotics can cause significant injury to the microbiome which leads to an increased risk of CDI and rCDI. Ongoing perturbations of the microbiome perpetuate this risk. Antibiotic treatments for CDI can kill C difficile but also can impact the microbiome. Microbiome therapeutics are effective in restoring the function of the gut microbiota and re-establishing colonization resistance. The field of microbiome therapeutics is evolving with newer, more refined, modalities in development.}, }
@article {pmid40348275, year = {2025}, author = {Hassib, L and Kanashiro, A and Pedrazzi, JFC and Vercesi, BF and Higa, S and Arruda, &#xcd; and Soares, Y and de Jesus de Souza, A and Barichello, T and Guimarães, FS and Ferreira, FR}, title = {Microbiota-based therapies as novel targets for autism spectrum disorder: A systematic review and meta-analysis.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {}, number = {}, pages = {111385}, doi = {10.1016/j.pnpbp.2025.111385}, pmid = {40348275}, issn = {1878-4216}, abstract = {BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by persistent deficits in social interaction and communication. Emerging evidence suggests that alterations in the gut-brain axis play a key role in the pathophysiology of ASD, and that microbiota-targeted interventions may offer therapeutic benefits. However, no clear consensus has been reached regarding the effectiveness of these strategies in ameliorating behavioral characteristics. This systematic review and meta-analysis (PROSPERO registration ID: CRD42023494067) aimed to evaluate the impact of microbiota-based interventions-including synbiotics, prebiotics, single-strain probiotics, probiotic blends, and fecal microbiota transplantation (FMT)-on behavioral outcomes in individuals with ASD, with particular emphasis on social functioning.<br><br>RESULTS: Of the 373 records initially identified, 20 studies met the inclusion criteria, comprising 16 randomized controlled trials and 4 open-label studies. The overall effect size indicated a statistically significant improvement in ASD-related behavioral symptoms following microbiota manipulation (Hedges' g&#x202f;=&#x202f;0.47; 95&#x202f;% CI: 0.30-0.64; p&#x202f;<&#x202f;0.001; I[2]&#x202f;=&#x202f;33.01&#x202f;%), representing a small but clinically relevant effect. Heterogeneity was classified as moderate. Among the interventions, FMT and probiotic blends yielded the most substantial effects. All major limitations of the current studies were thoroughly addressed and discussed to guide future experimental designs. Additionally, we examined preclinical evidence supporting the involvement of neural, immune, and metabolic pathways in mediating the observed behavioral improvements.<br><br>CONCLUSIONS: Our findings support the potential of microbiota-based therapies as a promising and well-tolerated strategy for improving behavioral symptoms in individuals with ASD. FMT and multi-strain probiotic formulations appear particularly effective. Nevertheless, further high-quality randomized controlled trials-especially involving FMT-are urgently needed to validate these results and guide clinical implementation. Thus, these findings provide a critical foundation for future investigations seeking to refine microbiota-based interventions and uncover the underlying mechanisms through which they influence ASD-related behaviors.}, }
@article {pmid40348054, year = {2025}, author = {Meher, R}, title = {From 'Aww to Wow': Emerging role of transfusion medicine in fecal microbiota transplantation.}, journal = {Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tracli.2025.05.004}, pmid = {40348054}, issn = {1953-8022}, }
@article {pmid40341264, year = {2025}, author = {Wang, X and Li, T and Dong, L and Li, Y and Ding, H and Wang, J and Xu, Y and Sun, W and Li, L}, title = {Exploring the lipid-lowering effects of cinnamic acid and cinnamaldehyde from the perspective of the gut microbiota and metabolites.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo00384a}, pmid = {40341264}, issn = {2042-650X}, abstract = {The increasing incidence and associated metabolic complications pose major challenges in the treatment of hyperlipidaemia. Cinnamon is a food and medicinal resource associated with lipid metabolism, but the mechanism by which its active components, cinnamic acid (CA) and cinnamaldehyde (CM), alleviate hyperlipidaemia remains unclear. Biochemical, pathological, gut microbiota, and metabolomic analyses were performed to investigate the effects of CA and CM on HFD-fed mice and the underlying mechanisms involved. Supplementation with CA and CM reduced body weight, liver, and adipose tissue accumulation in HFD-induced mice; improved glucose and lipid metabolism; and decreased inflammation and oxidative stress levels, with CM showing superior efficacy. Faecal microbiota transplantation confirmed that the therapeutic effect was closely related to core gut bacteria and metabolites. Specifically, CA and CM inhibited the growth of lipid metabolism-related genera (e.g., Turicibacter and Romboutsia) and metabolites (e.g., PC, LysoPCs, prostaglandin E2, and arachidonic acid) while promoting the growth of beneficial genera (e.g., Oscillospiraceae and Colidextribacter) and metabolites (e.g., linoleic acid, phytosphingosine, and stercobilin). Additionally, Spearman's correlation analysis revealed that serum and hepatic lipids, as well as inflammatory factors, were positively correlated with Erysipelatoclostridium, Turicibacter, Eubacterium fissicatena, Enterorhabdus, cervonoyl ethanolamide, and acetoxystachybotrydial acetate, whereas they were negatively correlated with Lachnospiraceae NK4A136, stercobilin, LysoPE (15:0/0:0), and phytosphingosine. In contrast, hepatic oxidative stress markers exhibited the opposite correlation pattern. In conclusion, CA and CM have the potential to regulate the core gut microbiota and metabolites to improve lipid metabolism and decrease related inflammation and oxidative stress levels.}, }
@article {pmid40337926, year = {2025}, author = {Shu, Y and Jiang, H and Gao, X and Hong, P and Wang, Q and Ruan, Y and Wu, H and He, J}, title = {Microcystin-LR Induces Lipid Metabolism Disorder in Pelophylax nigromaculatus Tadpoles via the Gut-Liver Axis.}, journal = {Environmental science &amp; technology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.est.4c12957}, pmid = {40337926}, issn = {1520-5851}, abstract = {Disruption of lipid homeostasis in aquatic animals poses serious health risks, including tissue damage and systemic metabolic dysfunction. The precise mechanisms by which microcystin-LR, a potent cyanotoxin, disrupts lipid metabolism in amphibian tadpoles remain unclear. In this study, tadpoles (Pelophylax nigromaculatus) were exposed to MC-LR and fecal microbiota transplantation (FMT) experiments were performed to investigate whether or how MC-LR at environmental concentrations interfered with tadpole lipid metabolism from the perspective of the gut microbiota-gut-liver axis. Following exposure, the liver exhibited significant inflammation, hypertrophy, and fibrosis, accompanied by elevated serum lipid levels. Furthermore, the expression levels of the farnesoid X receptor (FXR), a nuclear receptor, were significantly downregulated. Molecular docking and molecular dynamics simulations indicated a strong and stable binding between FXR and MC-LR. Moreover, MC-LR suppressed liver FXR expression or activity, triggering: (1) upregulation of sterol regulatory element-binding protein 1 (SREBP1)-mediated triglyceride (TG) synthesis, (2) inhibition of free fatty acid (FFA) β-oxidation, and (3) activation of SREBP2-dependent bile acid biosynthesis. Moreover, MC-LR altered the composition of gut microbiota and specific bile acid levels (e.g., taurocholic acid and glycochenodeoxycholic acid) in the gut, thereby interfering with hepatic lipid metabolism, as evidenced by FMT-induced hepatic lipid accumulation in recipient tadpoles. These findings identify FXR as a potentially key molecular target for MC-LR and suggest that changes in bile acid levels of intestinal microbiota metabolism also may be an important pathway driving hepatic lipid dysregulation in amphibians exposed to environmental concentrations of MC-LR.}, }
@article {pmid40336226, year = {2025}, author = {Cui, C and Gao, S and Shi, J and Wang, K}, title = {Gut-Liver Axis: The Role of Intestinal Microbiota and Their Metabolites in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {Gut and liver}, volume = {}, number = {}, pages = {}, doi = {10.5009/gnl240539}, pmid = {40336226}, issn = {2005-1212}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as one of the most prevalent chronic liver diseases globally, and its pathogenesis is closely linked to the imbalance of intestinal microbiota and their metabolites. This article reviews the mechanisms through which intestinal microbiota influence the progression of MASLD via the gut-liver axis, elaborating on the complex roles of immune cell hyperactivation, impaired intestinal barrier function, and intestinal microbial metabolites such as short-chain fatty acids and bile acids. The imbalance of intestinal microbiota not only directly promotes the development of MASLD but also further exacerbates disease progression through abnormalities in their metabolites. Various novel therapeutic strategies are being actively developed on the basis of gut-liver axis theory, including probiotic/prebiotic/synbiotic treatment, fecal microbiota transplantation, and targeted drug therapy. These strategies aim to precisely regulate microbial homeostasis and improve glucose and lipid metabolism, thereby alleviating hepatic inflammation and fibrosis and optimizing the therapeutic outcomes of patients with MASLD. In the future, as research progresses, we will further uncover the interaction mechanisms between intestinal microbiota and MASLD and continuously explore more effective treatment methods, with the goal of improving the prognosis and quality of life for MASLD patients.}, }
@article {pmid40335640, year = {2025}, author = {Kellermayer, R and Nagy-Szakal, D and Ihekweazu, FD and Luna, RA and Versalovic, J}, title = {Mucosal disease activity may predict response to fecal microbiota transplantation in patients with ulcerative colitis.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {40335640}, issn = {1530-0447}, }
@article {pmid40335161, year = {2025}, author = {Mela, V and Heras, V and Iesmantaite, M and García-Martín, ML and Bernal, M and Posligua-García, JD and Subiri-Verdugo, A and Martínez-Montoro, JI and Gómez-Pérez, AM and Banderas, B and Moreno Indias, I and Tinahones, FJ}, title = {Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-335353}, pmid = {40335161}, issn = {1468-3288}, abstract = {BACKGROUND: Obesity-related cognitive decline is linked to gut microbiota dysbiosis, with emerging evidence suggesting that dietary interventions may ameliorate cognitive impairment via gut-brain axis modulation. The role of microglial cells in this process remains underexplored.<br><br>OBJECTIVE: To investigate how diet-induced changes in gut microbiota influence cognitive function in individuals with obesity and their microglial activity, and to determine the impact of specific dietary interventions.<br><br>DESIGN: This study included 96 participants with obesity who were randomised into three dietary intervention groups: Mediterranean diet (Med), alternate-day fasting (ADF) and ketogenic diet (Keto). Cognitive performance and microbiota composition were assessed pre-intervention and post-intervention. The effects of microbiota-related changes on microglial function were further evaluated in mice models through faecal transplantation and in vitro model with microbiota exosome treatment.<br><br>RESULTS: Both the Keto and ADF groups demonstrated significant weight loss, but cognitive performance improved most notably in the ADF group, in association with reduced inflammation. Diet-related microbiota composition was correlated with the cognitive outcomes in the human study. Mice models confirmed that the cognitive benefits of ADF were microbiota-dependent and linked to enhanced microglial phagocytic capacity and reduced inflammation, accompanied by changes in microglia morphology.<br><br>CONCLUSION: Fasting-induced modifications in gut microbiota contribute to cognitive improvement in individuals with obesity, with microglial cells playing a crucial mediatory role. Among the interventions, ADF most effectively enhanced microglial function and cognitive performance, suggesting its potential as a therapeutic strategy for obesity-related cognitive decline. Further studies are required to fully elucidate the underlying mechanisms.<br><br>TRIAL REGISTRATION NUMBER: NCT04453150.}, }
@article {pmid40334428, year = {2025}, author = {Gu, S and Chen, C and Wang, J and Wang, Y and Zhao, L and Xiong, Z and Zhang, H and Deng, T and Pan, Q and Zheng, Y and Li, Y}, title = {Camellia Japonica Radix modulates gut microbiota and 9(S)-HpODE-mediated ferroptosis to alleviate oxidative stress against MASLD.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {143}, number = {}, pages = {156806}, doi = {10.1016/j.phymed.2025.156806}, pmid = {40334428}, issn = {1618-095X}, abstract = {BACKGROUND: Camellia japonica radix (CJR), derived from the root of Camellia japonica L., has the potential to function as an herbal tea substitute for the prevention and intervention of metabolic dysfunction-associated steatotic liver disease (MASLD). It can provide systemic therapeutic benefits, boast a favorable safety profile, facilitate convenient consumption, and support long-term applicability. Despite its potential, research on CJR remains limited.<br><br>PURPOSE: The aim of this study aims is to elucidate the therapeutic mechanisms of CJR in MASLD, thereby providing evidence to support its clinical application.<br><br>METHODS: The therapeutic effects of CJR were evaluated using a water-supplementation model in MASLD mice. Integrated microbiome, transcriptome, proteome, and metabolome analyses were employed to comprehensively explore the mechanisms involved. A drug-target pull-down assay was performed to identify specific protein targets of small molecule metabolites in vitro. Fecal microbiota transplantation in antibiotic-treated ABX mice was conducted to confirm the critical role of gut microbiota and its metabolites. Furthermore, customized medicated feed supplemented with linoleic acid was used to explore the intervention effect of its metabolite, 9(S)-HpODE, as well as to evaluate its dietary intervention potential.<br><br>RESULTS: This present study explicitly elucidates the efficacy of CJR extract in alleviating hepatic inflammation and steatosis in a MASLD model mice, with its pharmacological mechanism associated with gut microbiota, linoleic acid metabolism, and GPX4-mediated ferroptosis. Notably, 9(S)-HpODE was discovered to be a key metabolite of linoleic acid, which could target both KEAP1 and SLC7A11, bidirectionally regulating GPX4-mediated ferroptosis, while acting as a signaling molecule at low doses to induce redox adaptation via oxidative preconditioning, thus ameliorating oxidative stress in MASLD.<br><br>CONCLUSION: Our findings indicate that both CJR and linoleic acid exhibit significant potential as dietary interventions for the management of MASLD, offering promising avenues for future research and clinical application.}, }
@article {pmid40333159, year = {2025}, author = {Gao, Y and Lou, Y and Hui, Y and Chen, H and Sang, H and Liu, F}, title = {Characterization of the Gut Microbiota in Patients with Psoriasis: A Systematic Review.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {40333159}, issn = {2076-0817}, support = {22LCYY-QH10//Jinling Hospital/ ; }, mesh = {Humans ; *Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Probiotics/administration &amp; dosage ; *Psoriasis/microbiology/therapy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Background: Psoriasis is a prevalent and persistent inflammatory disorder with systemic manifestations. Emerging evidence implicates the gut microbiota in regulating inflammatory responses, metabolic pathways, and immune homeostasis. This review synthesizes current evidence on gut microbiota dysbiosis in psoriasis and evaluates the therapeutic potential of probiotics and fecal microbiota transplantation (FMT) in disease management. Method: Following PRISMA guidelines, we systematically reviewed studies investigating gut microbiome profiles in psoriasis through the MEDLINE, EMBASE, and Web of Science databases (January 2015-December 2024). Included studies utilized 16S rRNA gene sequencing or metagenomic analyses for microbial characterization. Results: Comparative analyses revealed distinct gut microbiota patterns in psoriasis patients compared with healthy controls, although specific microbial signatures exhibited inconsistencies across studies. Notably, interventions modulating gut microbiota composition-particularly probiotic supplementation-demonstrated measurable improvements in psoriasis severity scores and inflammatory markers. Conclusions: Gut microbiome modulation represents a promising therapeutic strategy for psoriasis; however, current evidence highlights the need for standardized microbial analysis methodologies and larger longitudinal studies to establish causality. Future research should prioritize the functional characterization of microbiota-host interactions to optimize therapeutic applications.}, }
@article {pmid40332367, year = {2025}, author = {Ionescu, VA and Diaconu, CC and Gheorghe, G and Mihai, MM and Diaconu, CC and Bostan, M and Bleotu, C}, title = {Gut Microbiota and Colorectal Cancer: A Balance Between Risk and Protection.}, journal = {International journal of molecular sciences}, volume = {26}, number = {8}, pages = {}, pmid = {40332367}, issn = {1422-0067}, mesh = {Humans ; *Colorectal Neoplasms/microbiology/prevention &amp; control/immunology/etiology ; *Gastrointestinal Microbiome ; Animals ; Risk Factors ; Probiotics ; }, abstract = {The gut microbiome, a complex community of microorganisms residing in the intestinal tract, plays a dual role in colorectal cancer (CRC) development, acting both as a contributing risk factor and as a protective element. This review explores the mechanisms by which gut microbiota contribute to CRC, emphasizing inflammation, oxidative stress, immune evasion, and the production of genotoxins and microbial metabolites. Fusobacterium nucleatum, Escherichia coli (pks+), and Bacteroides fragilis promote tumorigenesis by inducing chronic inflammation, generating reactive oxygen species, and producing virulence factors that damage host DNA. These microorganisms can also evade the antitumor immune response by suppressing cytotoxic T cell activity and increasing regulatory T cell populations. Additionally, microbial-derived metabolites such as secondary bile acids and trimethylamine-N-oxide (TMAO) have been linked to carcinogenic processes. Conversely, protective microbiota, including Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii, contribute to intestinal homeostasis by producing short-chain fatty acids (SCFAs) like butyrate, which exhibit anti-inflammatory and anti-carcinogenic properties. These beneficial microbes enhance gut barrier integrity, modulate immune responses, and inhibit tumor cell proliferation. Understanding the dynamic interplay between pathogenic and protective microbiota is essential for developing microbiome-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, to prevent or treat CRC. Future research should focus on identifying microbial biomarkers for early CRC detection and exploring personalized microbiome-targeted therapies. A deeper understanding of host-microbiota interactions may lead to innovative strategies for CRC management and improved patient outcomes.}, }
@article {pmid40329424, year = {2025}, author = {Ni, Q and Xia, L and Huang, Y and Yuan, X and Gu, W and Chen, Y and Wang, Y and Nian, M and Wu, S and Cai, H and Huang, J}, title = {Gut microbiota dysbiosis orchestrates vitiligo-related oxidative stress through the metabolite hippuric acid.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {112}, pmid = {40329424}, issn = {2049-2618}, support = {82203909//National Natural Science Foundation of China grant/ ; 82100513//National Natural Science Foundation of China grant/ ; GZC20233592//Postdoctoral Fellowship Program of CPSF/ ; 22BJQN003//Youth Talent Support Program of Air Force Medical Center/ ; 21ZT10//Boost Program for Young Doctor of Air Force Medical Center/ ; 2023JH6/100100034//Science and Technology Foundation of Liaoning Province guided by the central government in 2023/ ; }, mesh = {*Vitiligo/microbiology/metabolism/pathology ; *Oxidative Stress ; *Gastrointestinal Microbiome/physiology ; Animals ; *Dysbiosis/microbiology/metabolism ; Mice ; Humans ; *Hippurates/metabolism/blood ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; Male ; Skin/metabolism/pathology ; Fecal Microbiota Transplantation ; Female ; Melanocytes/metabolism ; Probiotics/administration &amp; dosage ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Vitiligo, a depigmenting autoimmune skin disease characterized by melanocyte dysfunction or death, is known to be associated with an imbalance in gut microbiota. Oxidative stress plays a critical role in the pathogenesis of vitiligo. However, the complex promising interaction between abnormal accumulation of reactive oxygen species (ROS) in the skin and gut microbiota has remained unclear.<br><br>RESULTS: Here, we compared transcriptome data of vitiligo lesions and normal skin and identified a high expression of oxidative stress-related genes in vitiligo lesions. We also established a vitiligo mouse model and found that the presence of gut microbiota influenced the expression of ROS-related genes. Depletion of gut microbiota reduced abnormal ROS accumulation and mitochondrial abnormalities in melanocytes, significantly improving depigmentation. Our findings from manipulating gut microbiota through cohousing, fecal microbiota transplantation (FMT), and probiotic supplementation showed that transferring gut microbiota from mice with severe vitiligo-like phenotypes exacerbated skin depigmentation while probiotics inhibited its progression. Targeted metabolomics of fecal, serum, and skin tissues revealed gut microbiota-dependent accumulation of hippuric acid, mediating excessive ROS in the skin. Elevated serum hippuric acid levels were also confirmed in vitiligo patients. Additionally, a microbiota-dependent increase in intestinal permeability in vitiligo mice mediated elevated hippuric acid levels, and we found that hippuric acid could directly bind to ROS-related proteins (NOS2 and MAPK14).<br><br>CONCLUSIONS: Our results suggested the important role of gut microbiota in regulating vitiligo phenotypes and oxidative stress. We identified hippuric acid, a gut microbiota-host co-metabolite, as a critical mediator of oxidative stress in vitiligo skin and its binding targets (NOS2 and MAPK14), resulting in oxidative stress. Validation in a small human cohort suggested that hippuric acid could serve as a novel diagnostic biomarker and therapeutic target for vitiligo. These findings provided new insights into how gut microbiota regulates skin oxidative stress in vitiligo and suggested potential treatment strategies for the disease. Video Abstract.}, }
@article {pmid40329327, year = {2025}, author = {Ding, L and Qi, K and Zhou, Y and Li, Q and Liu, M and Hu, N and Wang, J and Qiu, J and Deng, X and Xu, L}, title = {Ingestion of Artemisia argyit essential oil combats Salmonella pullorum infections by altering gut microbiota composition in chicks.}, journal = {Veterinary research}, volume = {56}, number = {1}, pages = {98}, pmid = {40329327}, issn = {1297-9716}, support = {2023YFD1800903//National Key Research and Development Program of China/ ; U22A20523//National Natural Science Foundation of China/ ; JJKH20250155KJ//Scientific Research Project of the Education Department of Jilin Province/ ; 2023-JCXK-01//Fundamental Research Funds for the Central Universities/ ; 2024T170330//China Postdoctoral Science Foundation/ ; 2024M751096//China Postdoctoral Science Foundation/ ; GZB20240268//postdoctoral Fellowship Program (Grade B) of China Postdoctoral Science Foundation/ ; }, mesh = {Animals ; *Artemisia/chemistry ; *Gastrointestinal Microbiome/drug effects ; *Chickens ; *Oils, Volatile/pharmacology/administration &amp; dosage ; *Poultry Diseases/microbiology/prevention &amp; control/drug therapy ; *Salmonella Infections, Animal/microbiology/prevention &amp; control/drug therapy ; Fecal Microbiota Transplantation/veterinary ; Animal Feed/analysis ; *Salmonella/drug effects/physiology ; Dietary Supplements/analysis ; *Plant Oils/pharmacology ; Diet/veterinary ; }, abstract = {Pullorum disease, caused by Salmonella pullorum (S. pullorum), is a highly contagious illness affecting the poultry industry. Emerging evidence suggests that Artemisia argyit essential oil can influence the composition of gut microbes in the host, thereby promoting overall health. However, the specific mechanisms by which Artemisia argyit essential oil modulates gut microbiota to combat S. pullorum infection remains unclear. This study explored the effectiveness of various doses of Artemisia argyit essential oil in preventing S. pullorum infection in chicks. Our findings indicate that consuming this essential oil can mitigate the intestinal mucosal barrier damage and excessive inflammatory response caused by S. pullorum, as well as reverse the weight loss seen in infected chicks. Additionally, chicks that received faecal microbiota transplantation (FMT) from the gut microbiota of Artemisia argyit essential oil donors exhibited notable recovery from S. pullorum infections. This suggests that the observed protection may be linked to the modulation of gut microbiota. Furthermore, 16S rRNA sequencing revealed an increased abundance of Lactobacillus reuteri (L. reuteri), which along with the activation of Wnt/β-catenin pathways, played critical roles in the enhanced health of S. pullorum-infected chicks treated with Artemisia argyit essential oil. In summary, these findings highlight that the dietary inclusion of Artemisia argyit essential oil promotes the intestinal enrichment of L. reuteri, offering a promising strategy for the treatment and prevention of pullorum disease in chicks.}, }
@article {pmid40329009, year = {2025}, author = {Nobels, A and van Marcke, C and Jordan, BF and Van Hul, M and Cani, PD}, title = {The gut microbiome and cancer: from tumorigenesis to therapy.}, journal = {Nature metabolism}, volume = {}, number = {}, pages = {}, pmid = {40329009}, issn = {2522-5812}, support = {T.0032.25//Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)/ ; EOS: program no. 40007505//Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)/ ; WELBIO-CR-2022A-02//Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)/ ; }, abstract = {The gut microbiome has a crucial role in cancer development and therapy through its interactions with the immune system and tumour microenvironment. Although evidence links gut microbiota composition to cancer progression, its precise role in modulating treatment responses remains unclear. In this Review, we summarize current knowledge on the gut microbiome's involvement in cancer, covering its role in tumour initiation and progression, interactions with chemotherapy, radiotherapy and targeted therapies, and its influence on cancer immunotherapy. We discuss the impact of microbial metabolites on immune responses, the relationship between specific bacterial species and treatment outcomes, and potential microbiota-based therapeutic strategies, including dietary interventions, probiotics and faecal microbiota transplantation. Understanding these complex microbiota-immune interactions is critical for optimizing cancer therapies. Future research should focus on defining microbial signatures associated with treatment success and developing targeted microbiome modulation strategies to enhance patient outcomes.}, }
@article {pmid40328737, year = {2025}, author = {Hitch, TCA and Masson, JM and Pauvert, C and Bosch, J and Nüchtern, S and Treichel, NS and Baloh, M and Razavi, S and Afrizal, A and Kousetzi, N and Aguirre, AM and Wylensek, D and Coates, AC and Jennings, SAV and Panyot, A and Viehof, A and Schmitz, MA and Stuhrmann, M and Deis, EC and Bisdorf, K and Chiotelli, MD and Lissin, A and Schober, I and Witte, J and Cramer, T and Riedel, T and Wende, M and Winter, KA and Amend, L and Riva, A and Trinh, S and Mitchell, L and Hartman, J and Berry, D and Seitz, J and Bossert, LC and Grognot, M and Allers, T and Strowig, T and Pester, M and Abt, B and Reimer, LC and Overmann, J and Clavel, T}, title = {HiBC: a publicly available collection of bacterial strains isolated from the human gut.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {4203}, pmid = {40328737}, issn = {2041-1723}, support = {513892404//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 445552570//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 395357507//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 403224013//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 460129525//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Plasmids/genetics ; *Bacteria/isolation &amp; purification/classification/genetics ; Phylogeny ; Feces/microbiology ; }, abstract = {Numerous bacteria in the human gut microbiome remain unknown and/or have yet to be cultured. While collections of human gut bacteria have been published, few strains are accessible to the scientific community. We have therefore created a publicly available collection of bacterial strains isolated from the human gut. The Human intestinal Bacteria Collection (HiBC) (https://www.hibc.rwth-aachen.de) contains 340 strains representing 198 species within 29 families and 7 phyla, of which 29 previously unknown species are taxonomically described and named. These included two butyrate-producing species of Faecalibacterium and new dominant species associated with health and inflammatory bowel disease, Ruminococcoides intestinale and Blautia intestinihominis, respectively. Plasmids were prolific within the HiBC isolates, with almost half (46%) of strains containing plasmids, with a maximum of six within a strain. This included a broadly occurring plasmid (pBAC) that exists in three diverse forms across Bacteroidales species. Megaplasmids were identified within two strains, the pMMCAT megaplasmid is globally present within multiple Bacteroidales species. This collection of easily searchable and publicly available gut bacterial isolates will facilitate functional studies of the gut microbiome.}, }
@article {pmid40328388, year = {2025}, author = {Wang, J and Yang, L and Liu, L and Ren, J and Jiang, Z and Zhao, X and Jiao, L and Gao, Y and Guo, Y and Yu, T and Li, B and Li, Y and Tong, H}, title = {Pectin from Fructus Mori relieve oxidative stress and regulates gut microbiota in POF mice.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {143941}, doi = {10.1016/j.ijbiomac.2025.143941}, pmid = {40328388}, issn = {1879-0003}, abstract = {Pectin, a complex acidic heteropolysaccharide with diverse biological activities, is widely unilized in cosmetics and food industry. Fructus Mori (F. Mori), an important cultivated fruit, contains abundant pectin. In this study, a pectic polysaccharide (FPA1-1) was extracted from F. Mori through hot-water extraction, ethanol precipitation, and chromatographic purification. Structural analysis revealed that FPA1-1 was a rhamnogalacturonan-I (RG-I)-rich mixed pectin with a branching degree of 48.42 %. In vivo experiments, FPA1-1 (400 mg/kg) effectively shortened the oestrous cycle, reduced follicle stimulating hormone (FSH) level, promoted synthesis and secretion of estradiol hormone (E2) and luteinizing hormone (LH), suppressed serum interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels and improved antioxidant capacity in premature ovarian failure (POF) mice. Moreover, FPA1-1 modulated gut dysbiosis of POF mice by decreasing Firmicutes/ Bacteroidetes ratio and Desulfobacterota abundance at phylum level, enriching Bacteroides, Prevotellaceae, Parabacteroides, Alloprevotella, and Muribaculaceae abundance and inhibiting Desulfovibrionaceae proliferation. FPA1-1 treatment increased short-chain fatty acids (SCFAs) level. Antibiotic cocktail treatment and fecal microbiota transplantation (FMT) experiments confirmed that FPA1-1 ameliorates the ovarian function through altering the gut microbiota composition. These findings provided an experimental basis for further research and applications of F. mori pectin in female ovarian health.}, }
@article {pmid40326772, year = {2025}, author = {Chen, Z and Chai, S and Ding, Y and Pang, K and Dong, T and Dai, D and Wang, J and Wang, S and Liu, S}, title = {Gut microbiota modulates lung gene expression and metabolism to aid SD rats in adapting to low-pressure hypoxia.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0004525}, doi = {10.1128/spectrum.00045-25}, pmid = {40326772}, issn = {2165-0497}, abstract = {UNLABELLED: Hypoxia has long posed a serious threat to the health of both animals and humans, causing respiratory acidosis, metabolic disorders, systemic inflammation, oxidative stress damage, and other issues, thereby endangering life and limiting development in high-altitude areas. Gut microbiota plays a crucial role in life activities and hypoxia adaptation. We transplanted the gut microbiota from small mammals, plateau zokors (Myospalax baileyi), from the Qinghai-Tibetan plateau (3,500 m) to Sprague-Dawley (SD) rats housed in a hypobaric chamber (equivalent to 6,000 m altitude) for 30 days. The results showed that microbiota transplantation significantly reshaped the gut microbiota structure of the rats, notably increasing the abundance of short-chain fatty acid-producing bacteria Lachnospiraceae and Prevotellaceae, alleviating hypoxia and acidosis, reducing pulmonary hypertension and right ventricular hypertrophy, increasing the production of anti-inflammatory substances like indole-3-lactic acid, and reducing the generation of pro-inflammatory substances, such as histamine and uric acid. It also decreased the expression of inflammatory genes like lgE, TNFα, and IFN-γ in the lung. Fecal microbiota transplantation from plateau-specific species to low-altitude SD rats effectively altered metabolism, changed gene expression, decreased pulmonary artery pressure, and enhanced plateau adaptability. This study demonstrates the potential effectiveness of treating hypoxic pulmonary hypertension through microbiota transplantation and offers insights into improving hypoxia adaptation.<br><br>IMPORTANCE: We report the beneficial effects of FMT on respiratory capacity, lung metabolism, and lung gene expression in SD rats under hypoxic conditions. We revealed the inhibitory effects of gut microbiota on lung mast cells and histamine expression under hypoxic conditions. The study demonstrated the potential effectiveness of treating HPH through FMT and offers insights into improving hypoxia adaptation.}, }
@article {pmid40323507, year = {2025}, author = {Wadan, AS and El-Aziz, MKA and Ellakwa, DE}, title = {The microbiota-gut-brain-axis theory: role of gut microbiota modulators (GMMs) in gastrointestinal, neurological, and mental health disorders.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {40323507}, issn = {1432-1912}, abstract = {The modulation of gut microbiota presents promising therapeutic possibilities for various health conditions, ranging from gastrointestinal infections to neurodegenerative and mental health disorders. Among the available interventions, gut microbiota modulators (GMMs) such as probiotics and prebiotics have demonstrated significant potential in infection prevention and neuroprotection. Despite these encouraging findings, the clinical application of GMMs remains challenging due to safety concerns and inconsistent effectiveness across diverse patient populations. These factors create substantial barriers to the widespread adoption of microbiota-based therapies in clinical practice. To overcome these challenges and fully leverage the therapeutic potential of microbiota modulation, this review explores the feasibility of repurposing GMMs for managing multiple health disorders. A broad spectrum of microbiota-targeted strategies is examined, including dietary modifications, fecal microbiota transplantation, bacteriophage therapy, microbiome engineering, and immune system modulation. A particularly innovative approach involves integrating GMMs with pharmaceutical delivery systems to enhance therapeutic efficacy while mitigating potential adverse effects. This integrative strategy underscores the pivotal role of the gut microbiome in health and disease, supporting the development of precision medicine tailored to individual patient needs. By combining GMMs with targeted delivery mechanisms, this approach not only improves treatment effectiveness but also addresses critical concerns regarding safety and patient variability. Furthermore, this review outlines future research directions within the rapidly evolving field of microbiota modulation, emphasizing the necessity of comprehensive clinical trials and long-term safety evaluations. By critically assessing both the challenges and opportunities associated with microbiota-based interventions, this study provides a strategic framework for translating experimental research into viable clinical applications. A holistic approach to gut microbiota modulation has the potential to redefine treatment paradigms, offering personalized therapeutic strategies for a wide range of disorders and advancing the broader field of precision medicine.}, }
@article {pmid40321610, year = {2025}, author = {Dong, Z and Zhang, R and Shen, L and Ji, HF and He, H and Ji, X and Zhao, L}, title = {Gut Microbiota and Immunoglobulin A Nephropathy: Exploration of Dietary Intervention and Treatment Strategies.}, journal = {Food science &amp; nutrition}, volume = {13}, number = {5}, pages = {e70218}, pmid = {40321610}, issn = {2048-7177}, abstract = {Immunoglobulin A nephropathy (IgAN) is a primary glomerular disease characterized by the deposition of IgA. The pathogenesis of it is related to the dysbiosis of gut microbiota. Dysbiosis of gut microbiota influences mucosal immune response and systemic immune system, leading to glycosylation-deficient IgA1 (Gd-IgA1) increasing, which promotes the development of IgAN. Diet plays an important role in regulating gut microbiota and treating IgAN. In this review, we summarize the interplay between gut microbiota and IgAN, and their underlying mechanisms. We also describe the effects of dietary intake on IgAN, as well as the composition of gut microbiota. The progress on IgAN treatment mainly focuses on inhibiting or regulating the immune system. Moreover, therapeutic strategies related to gut microbiota such as dietary intervention, supplement of probiotics and prebiotics, as well as fecal microbiota transplantation (FMT) have shown the possibility of improving IgAN prognosis. Thus, exploration of the gut-kidney axis, the long-term effects of diet and microbiome is necessary to develop more effective treatment strategies.}, }
@article {pmid40321299, year = {2025}, author = {Pan, L and Xie, L and Yang, W and Feng, S and Mao, W and Ye, L and Cheng, H and Wu, X and Mao, X}, title = {The role of brain-liver-gut Axis in neurological disorders.}, journal = {Burns &amp; trauma}, volume = {13}, number = {}, pages = {tkaf011}, pmid = {40321299}, issn = {2321-3868}, abstract = {In recent years, with the increasing volume of related research, it has become apparent that the liver and gut play important roles in the pathogenesis of neurological disorders. Considering the interactions among the brain, liver, and gut, the brain-liver-gut axis has been proposed and gradually recognized. In this article, we summarized the complex network of interactions within the brain-liver-gut axis, encompassing the vagus nerve, barrier permeability, immunity and inflammation, the blood-brain barrier, gut microbial metabolites, the gut barrier, neurotoxic metabolites, and beta-amyloid (Aβ) metabolism. We also elaborated on the impact of the brain-liver-gut axis on various neurological disorders. Furthermore, we outline several therapies aimed at modulating the brain-liver-gut axis, including antibiotics, probiotics and prebiotics, fecal microbiota transplantation (FMT), vagus nerve stimulation (VNS), and dietary interventions. The focus is on elucidating possible mechanisms underlying neurological disorders pathogenesis and identifying effective treatments that are based on our understanding of the brain-liver-gut axis.}, }
@article {pmid40320851, year = {2025}, author = {Kim, KS and Yang, SY and Jeong, H and Hong, M and Noh, J and Koh, H and Lee, DW}, title = {Development of a Korean Nutrition Model for In Silico Gut Microbiome Analyses Integrated With Nutrigenomics.}, journal = {Molecular nutrition &amp; food research}, volume = {}, number = {}, pages = {e70090}, doi = {10.1002/mnfr.70090}, pmid = {40320851}, issn = {1613-4133}, support = {RS-2021-NR056579//Bio &amp; Medical Technology Development Program of the National Research Foundation (NRF) of Korea/ ; //Ministry of Science and ICT (MSIT)/ ; 20018770//Bioindustrial Technology Development Program of Korea/ ; //Ministry of Trade, Industry and Energy/ ; 2025-12-0026//Yonsei University Research Fund/ ; }, abstract = {The gut microbiome plays a crucial role in human health and disease, with diet serving as a critical determinant of microbial composition and metabolic function. However, most existing nutrition databases are Western-centric, lacking comprehensive dietary information for non-Western populations, including Koreans. This limitation hinders the accuracy of in silico gut microbiome analyses and microbiome-disease associations. We developed the Korean Nutrition Model (KNM) to enhance in silico microbiome analyses by incorporating detailed macronutrient and micronutrient compositions reflective of Korean dietary patterns. KNM was constructed using a decision algorithm that integrates data from the Ministry of Food and Drug Safety and FooDB. Comparative analysis with the European Nutrition Model revealed significant differences in carbohydrate and vitamin compositions, which in turn influenced microbial growth rates and metabolic fluxes in in silico simulations. We further evaluated gut microbiota differences between Korean and European cohorts, including healthy individuals and inflammatory bowel disease patients. Our findings demonstrate that using an appropriate, population-specific nutrition model significantly improves microbiome analyses, reducing the risk of false associations. This study underscores the importance of regionally tailored dietary models and provides a framework for enhancing global dietary models to facilitate precision nutrition and microbiome-based disease interventions.}, }
@article {pmid40317768, year = {2025}, author = {Kooij, KL and Andreani, NA and Keller, L and Trinh, S and van der Gun, L and Hak, J and Garner, K and Luijendijk, M and Drost, L and Danner, U and van Elburg, A and Dempfle, A and Seitz, J and Herpertz-Dahlmann, B and Baines, JF and Adan, RAH}, title = {Antibiotic-Induced Microbial Dysbiosis Worsened Outcomes in the Activity-Based Anorexia Model.}, journal = {The International journal of eating disorders}, volume = {}, number = {}, pages = {}, doi = {10.1002/eat.24452}, pmid = {40317768}, issn = {1098-108X}, support = {MIGBAN FKZ: 01EW1906A//ERA_Net/ ; 509492174//Deutsche Forschungsgemeinschaft/ ; }, abstract = {OBJECTIVE: Anorexia nervosa (AN) is a complex psychiatric disorder characterized by persistent dieting and reduced food intake, leading to significantly low body weight. Dysbiosis in the gut microbiome of patients with AN has been suggested to contribute to the pathogenesis. Here, we used fecal microbiota transplantation (FMT) in the activity-based anorexia (ABA) rat model to investigate the impact of AN-associated gut microbiota on disease-related outcomes.<br><br>METHOD: We validated the FMT in 12 Wistar rats by depleting the gut microbiome with antibiotics and transplanting two donors' fecal samples. We then transplanted fecal samples from four patients with AN or four healthy controls in 48 rats just before the ABA model exposure and included an antibiotic-only control group. During ABA, the rats had access to a running wheel and only 1.5&#x2009;h access to chow for 7&#x2009;days. We monitored body weight, body temperature, food intake, wheel revolutions, and gut microbiome biodiversity and composition.<br><br>RESULTS: The antibiotic treatment significantly depleted the rats' gut microbiome and subsequent transplantation made the rats' microbiome more similar to the donors' microbiome. The antibiotic-only group showed reduced survival, as well as lower body weight and temperature during ABA. Transplanted microbiota from patients with AN and healthy controls improved outcomes in the ABA model.<br><br>DISCUSSION: We do not find evidence that the microbiome of patients with AN differentially contributes to anorexia-like phenotypes based upon partial microbiome transplantation. However, the presence of a microbiome impacts the outcome of the ABA model.}, }
@article {pmid40316878, year = {2025}, author = {Shirzadi, P and Farokh, P and Osouli Meinagh, S and Izadi-Jorshari, G and Hajikarimloo, B and Mohammadi, G and Parvardeh, S and Nassiri-Asl, M}, title = {The Influence of the Probiotics, Ketogenic Diets, and Gut Microbiota on Epilepsy and Epileptic Models: A Comprehensive Review.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40316878}, issn = {1559-1182}, support = {01-33153//Shahid Beheshti University of Medical Sciences/ ; }, abstract = {About one-third of epilepsies are resistant to antiepileptic drugs; thus, uncovering new pathways in the pathophysiology of epilepsy can reduce the global disease burden. Probiotics are live, non-pathogenic microorganisms that benefit the host by regulating the gut microbiome. This review aims to study the effect of probiotics and ketogenic diets on gut microbiota and their potential as a therapy for epilepsy. We conducted a systematic search of the databases PubMed, Scopus, Embase, and the Web of Science for pertinent studies that have been published. Our search methodology was meticulously structured to be exhaustive, integrating targeted keywords and Boolean operators to guarantee the acquisition of all potentially pertinent articles. Probiotics interact with the gut microbiome, balance its composition, and influence the gut-brain axis. Moreover, they reduce neuroinflammation and oxidative stress. The ketogenic diet (KD) affects gut bacteria, influencing neurotransmitter levels and short-chain fatty acids (SCFAs), which play a role in the gut-brain axis. Studies have shown the positive effects of various probiotics in animal models of epilepsy. They demonstrate improvements in seizure activity, anxiety, and neuroinflammation. In human studies, probiotics reduced seizure frequency and enhanced quality of life in patients with drug-resistant epilepsy. We believe using probiotics or dietary interventions like KD could be a promising therapeutic strategy for managing epilepsy. This could reduce seizure frequency and make life better for patients with epilepsy.}, }
@article {pmid40316655, year = {2025}, author = {Neyrinck, AM and Ahmed, H and Leyrolle, Q and Leclercq, S and Amadieu, C and Meuronen, T and Layé, S and Cani, PD and Kärkkäinen, O and Bindels, LB and Hanhineva, K and Delzenne, NM}, title = {Fecal transplantation from humans with obesity to mice drives a selective microbial signature without impacting behavioral and metabolic health.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {15455}, pmid = {40316655}, issn = {2045-2322}, support = {ANR-19-NEUR-0003-03//Agence Nationale de la Recherche/ ; PDR T.0068.19 and PINT-MULTI R.8013.19//FNRS/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Obesity/microbiology/therapy/metabolism ; Humans ; *Gastrointestinal Microbiome ; Mice ; Male ; *Behavior, Animal ; Feces/microbiology ; Mice, Inbred C57BL ; Female ; Metabolomics ; Metabolome ; }, abstract = {Obesity is associated with alterations in the gut microbiome that may contribute to metabolic and mental health disturbances. Fecal microbiota transplantation (FMT) from humans to mice is a model proposed to study human microbiota-associated disorders. In this study, we investigated whether gut microbiota from human donors with obesity could affect behavior and metabolomic profiles of mice. Stools from donors with obesity and from lean donors were inoculated to antibiotic-pretreated mice fed a standard low-fat diet throughout the experiment. Obese-recipient mice exhibited a lower bacterial alpha-diversity and limited changes in specific taxa (e.g., an increase in Eubacterium) but were similar to lean-recipient mice in terms of dietary intake, body weight, fat mass, anxiety/depression-like behavior and glucose homeostasis. Non-targeted LC-MS metabolomic analysis revealed no change in the portal and cava serum samples. However, 1-methylnicotinamide, indole-3-acetic acid (I3A) and methyllysine were increased in the cecal content of obese-recipient compared to lean-recipient mice. Microbial metabolites derived from amino acids were positively correlated with Eubacterium. These results indicate that FMT from donors with obesity to mice fed chow diet (low in lipids) leads to minor but persistent change in intestinal microbial-derived metabolites, without recapitulating the metabolic and behavioral alterations of obesity.}, }
@article {pmid40316371, year = {2025}, author = {Werner, M and Vigani, A}, title = {The Microbiome in Critical Illness.}, journal = {The Veterinary clinics of North America. Small animal practice}, volume = {55}, number = {3}, pages = {443-458}, doi = {10.1016/j.cvsm.2025.01.008}, pmid = {40316371}, issn = {1878-1306}, mesh = {Animals ; *Critical Illness/therapy ; Dogs ; *Dog Diseases/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; *Cat Diseases/microbiology/therapy ; Cats ; Fecal Microbiota Transplantation/veterinary ; *Gastrointestinal Diseases/veterinary/microbiology/therapy ; }, abstract = {Evidence suggests that the intestinal microbiome may play an important role in the pathogenesis and progression of acute critical illness in humans and other mammals, although evidence in small animal medicine is sparse. Moreover, the intestinal microbiota plays many important metabolic roles (production of short-chain fatty acids, trimethylamine-N-oxide, and normal bile acid metabolism) and is crucial for immunity as well as defense against enteropathogens. The use of probiotics and fecal microbiota transplantation as instruments to modulate the intestinal microbiota seems to be safe and effective in studies on critically ill dogs with acute gastrointestinal diseases.}, }
@article {pmid40316177, year = {2025}, author = {Yin, Y and Guan, M and Wu, S and Cui, C and Wang, R and Zhao, X and Yang, X and Qiao, L and Li, Y and Zhang, C}, title = {Young fecal microbiota transplantation improves working memory in aged recipient rats by increasing interleukin-4 and interleukin-17 levels.}, journal = {Neuroscience research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neures.2025.04.005}, pmid = {40316177}, issn = {1872-8111}, abstract = {While transplanting the fecal microbiota from young to aged rodents has been extensively studied (that is, young FMT [yFMT]), its mechanism of alleviating working memory decline has not been fully elucidated. In this report, we aimed to investigate the effect of yFMT on the working memory of aged recipient rats performing delayed match-to-position (DMTP) tasks and the associated cellular and molecular mechanisms. The results revealed that yFMT mitigated the decline in DMTP task performance of aged recipients. This improvement was associated with a reshaped gut microbiota and increased levels of brain-derived neurotrophic factor, N-methyl-D-aspartate receptor subunit 1, and synaptophysin, enhancing synaptic formation and transmission. The remodeling of the gut microbiome influenced peripheral circulation and the hippocampus and medial prefrontal cortex by regulating the Th17/Treg ratio and microglial polarization. Ultimately, interleukin-4 and interleukin-17 emerged as potential key molecules driving the beneficial effects of FMT. These observations provide new insights into the gutbrain axis, emphasizing the connection between the gut and brain through the circulation system, and suggest an immunological mechanism that may help reverse age-related declines in the gut microbiota.}, }
@article {pmid40316082, year = {2025}, author = {Qiu, MT and Zhou, L and Wang, XY and Li, ZP and Wei, MX and Zeng, ZH and Cheng, J and Xu, GH and Zhu, JX and Yi, LT}, title = {Anti-colitis comparison of polysaccharides and anthocyanins extracted from black wolfberry based on microbiomics, immunofluorescence and multi-cytokines profile analysis.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {143700}, doi = {10.1016/j.ijbiomac.2025.143700}, pmid = {40316082}, issn = {1879-0003}, abstract = {Black wolfberry (Lycium ruthenicum) is a widely consumed food known for its pharmacological properties, particularly its anti-inflammatory and antioxidant effects. This study investigates the therapeutic potential of black wolfberry polysaccharides (LRP) and anthocyanins (LRA) in treating ulcerative colitis, a chronic inflammatory bowel disease. Using a DSS-induced mouse model of colitis, we administered varying doses of LRP and LRA and evaluated their effects on disease activity, inflammation, gut barrier function, and microbiota composition. LRP demonstrated dose-dependent efficacy, with the 200 mg/kg dose showing the most significant reduction in the disease activity index (DAI), improvement in histopathology, and restoration of tight junction protein expression. In contrast, LRA exhibited an inverted U-shaped response, with the 100 mg/kg dose being the most effective. Additionally, LRP treatment modulated cytokine levels, promoting an anti-inflammatory response, and significantly restored gut microbiota balance by increasing Muribaculaceae and Limosilactobacillus while reducing Bacteroides and Helicobacter. Fecal microbiota transplantation (FMT) experiments further confirmed that the therapeutic effects of LRP are microbiota-dependent. These findings suggest that LRP, a polysaccharide derived from black wolfberry, offers a dietary intervention for colitis through immune modulation and gut microbiota restoration.}, }
@article {pmid40315641, year = {2025}, author = {Wei, FH and Xie, WY and Zhao, PS and Ji, ZH and Gao, F and Chen, CZ and Zhang, Z and Gao, W and Yuan, B}, title = {Crataegus pinnatifida polysaccharide alleviates DSS-induced colitis in mice by regulating the intestinal microbiota and enhancing arginine biosynthesis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {142}, number = {}, pages = {156794}, doi = {10.1016/j.phymed.2025.156794}, pmid = {40315641}, issn = {1618-095X}, abstract = {BACKGROUND: The development of effective and safe dietary supplements is essential for both the prevention and management of ulcerative colitis (UC), as its pathogenesis is intricate and difficult to completely resolve. Crataegus pinnatifida, a medicinal food with a long history of use, has broad medicinal value. Recent research has revealed promising insights into the role of polysaccharide derived from Crataegus pinnatifida on modulating short-chain fatty acids (SCFAs) to alleviate UC inflammation. However, the mechanisms by which CPP regulates the intestinal microbiota and key metabolites during the antagonistic phase of UC have yet to be elucidated.<br><br>OBJECTIVE: This research elucidated the protective role of CPP in relation to UC, highlighted the mechanisms through which CPP operates, particularly regarding gut microbiota and metabolism, and offered a theoretical foundation for the potential use of CPP as a dietary supplement aimed at preventing UC.<br><br>METHODS: The impact of CPP on acute UC induced by 3 % DSS in mice was examined through the evaluation of the disease activity index, measurement of colon length, and observation of body weight changes. Enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory factor levels in both serum and colon, as well as to assess oxidative stress mediators. The intestinal histological damage, mucus layer damage and the level of tight junction protein were analyzed by histopathological staining and western blot (WB). The impact of gut microbiota on CPP in colitis was evaluated using 16S rRNA sequencing, microbiota depletion experiments, and fecal microbiota transplantation (FMT) studies. The key metabolic pathways and key metabolites affected by CPP in the treatment of UC were analyzed through untargeted metabolomics sequencing, ELISA, and WB assays.<br><br>RESULTS: Prophylactic dietary supplementation with Crataegus pinnatifida polysaccharide (CPP) notably reduced the fundamental clinical manifestations of UC induced by DSS, including DAI score, reduced colon length, and weight loss, as well as inflammation and oxidative stress. CPP promoted the expression of Claudin-1, ZO-1 and Occludin and promoted mucin secretion, which contributed to the mitigation of intestinal barrier damage caused by DSS. 16S sequencing results and metabolomics results revealed that CPP intervention upregulated the relative abundance of Lactobacillus, thereby reshaping the intestinal microbiota and activate the arginine biosynthesis pathway. The results of fecal microbiota transplantation and antibiotic clearance experiments indicated that the alleviating effect of CPP on UC was dependent on the intestinal microbiota and this alleviating effect was transferred through fecal microbiota transplantation. Mechanistically, CPP indirectly promoted the expression of the rate-limiting enzyme argininosuccinate synthase 1 (ASS1) in the intestinal Arginine biosynthesis pathway by reshaping the intestinal microbiota, thereby increasing intestinal Arginine level and alleviating the inflammatory response and oxidative stress induced by DSS and intestinal barrier damage.<br><br>CONCLUSION: Our research findings demonstrate that CPP is a plant-derived polysaccharide that alleviates UC by modulating the gut microbiota and enhancing arginine biosynthesis.}, }
@article {pmid40314722, year = {2025}, author = {Castagnoli, R and Pala, F and Subramanian, P and Oguz, C and Schwarz, B and Lim, AI and Burns, AS and Fontana, E and Bosticardo, M and Corsino, C and Angelova, A and Delmonte, OM and Kenney, H and Riley, D and Smith, G and Ott de Bruin, L and Oikonomou, V and Dos Santos Dias, L and Fink, D and Bohrnsen, E and Kimzey, CD and Marseglia, GL and Alva-Lozada, G and Bergerson, JRE and Brett, A and Brigatti, KW and Dimitrova, D and Dutmer, CM and Freeman, AF and Ale, H and Holland, SM and Licciardi, F and Pasic, S and Poskitt, LE and Potts, DE and Dasso, JF and Sharapova, SO and Strauss, KA and Ward, BR and Yilmaz, M and Kuhns, DB and Lionakis, MS and Daley, SR and Kong, HH and Segre, JA and Villa, A and Pittaluga, S and Walter, JE and Vujkovic-Cvijin, I and Belkaid, Y and Notarangelo, LD}, title = {Immunopathological and microbial signatures of inflammatory bowel disease in partial RAG deficiency.}, journal = {The Journal of experimental medicine}, volume = {222}, number = {8}, pages = {}, pmid = {40314722}, issn = {1540-9538}, support = {U01 DK062413/DK/NIDDK NIH HHS/United States ; HHSN316201300006W/75N93022F00001/HH/HHS/United States ; //National Institute of Allergy and Infectious Diseases/ ; U01DK062413/DK/NIDDK NIH HHS/United States ; DP1HL174182/HL/NHLBI NIH HHS/United States ; 831262//Crohn's &amp; Colitis Foundation Career Development/ ; AI001222/NH/NIH HHS/United States ; DP1 HL174182/HL/NHLBI NIH HHS/United States ; //Fondazione Ghislieri/ ; //Cedars-Sinai Medical Center/ ; }, mesh = {Animals ; *Inflammatory Bowel Diseases/immunology/microbiology/pathology/genetics ; *Homeodomain Proteins/genetics ; Humans ; Mice ; Female ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome ; Bone Marrow Transplantation ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; Mice, Inbred C57BL ; }, abstract = {Partial RAG deficiency (pRD) can manifest with systemic and tissue-specific immune dysregulation, with inflammatory bowel disease (IBD) in 15% of the patients. We aimed at identifying the immunopathological and microbial signatures associated with IBD in patients with pRD and in a mouse model of pRD (Rag1w/w) with spontaneous development of colitis. pRD patients with IBD and Rag1w/w mice showed a systemic and colonic Th1/Th17 inflammatory signature. Restriction of fecal microbial diversity, abundance of pathogenic bacteria, and depletion of microbial species producing short-chain fatty acid were observed, which were associated with impaired induction of lamina propria peripheral Treg cells in Rag1w/w mice. The use of vedolizumab in Rag1w/w mice and of ustekinumab in a pRD patient were ineffective. Antibiotics ameliorated gut inflammation in Rag1w/w mice, but only bone marrow transplantation (BMT) rescued the immunopathological and microbial signatures. Our findings shed new light in the pathophysiology of gut inflammation in pRD and establish a curative role for BMT to resolve the disease phenotype.}, }
@article {pmid40314681, year = {2025}, author = {Li, X and Su, K and He, Y and Shao, S and Lan, L and Zhang, Q and Li, L}, title = {Knowledge Mapping of International Microbiota Research: Analyzing Thirty-Year Citation Classics and Exploring Future Expectations.}, journal = {The new microbiologica}, volume = {48}, number = {1}, pages = {46-59}, pmid = {40314681}, issn = {1121-7138}, mesh = {Humans ; *Bibliometrics ; *Biomedical Research ; Gastrointestinal Microbiome ; *Microbiota ; }, abstract = {Microbiota research has rapidly emerged as a pivotal field, with over 250,000 publications and more than ten million citations recorded in the Web of Science Core Collection database by 2024. There were 1682 original microbiota citation classics (each receiving 400 citations or more) identified over the past three decades, totaling 1,559,594 citations and averaging 927 citations per paper. Collaborative efforts in the production of these citation classics involved 87 out of 89 participating countries and 2107 out of 2142 institutions. The USA, various European countries, and China emerged as the leading contributors to this burgeoning research area. Jeffrey I. Gordon, Rob Knight, and Curtis Huttenhower were the prominent figures in microbiota research. Author keywords were analyzed, which revealed a notable shift in research focus from environmental microorganisms to human gut microbiota. Advances such as high-throughput 16S rRNA sequencing and metagenomics expanded the scope of investigations into host-microbiota interactions. Current research interests encompass exploring mechanisms underlying gut-X-axis conditions, including inflammatory bowel disease, obesity, diabetes, colorectal cancer, liver diseases, and neurological disorders. Moreover, environmental exposures have been evidenced to alter gut microbiota and metabolites, contributing a novel research direction. Future research direction is also anticipated to delve further into biosynthetic gene engineering technologies aimed at microbial interventions, including probiotics and fecal microbiota transplantation. This study outlines the evolving landscape of microbiota research and provides valuable insights to inform future investigations within the field.}, }
@article {pmid40314129, year = {2025}, author = {Xiao, K and Li, K and Xiao, K and Yang, J and Zhou, L}, title = {Gut Microbiota and Hepatocellular Carcinoma: Metabolic Products and Immunotherapy Modulation.}, journal = {Cancer medicine}, volume = {14}, number = {9}, pages = {e70914}, pmid = {40314129}, issn = {2045-7634}, support = {21MC1930500//Shanghai Clinical Research Center of Traditional Chinese Medicine Oncology, Science and Technology Commission of Shanghai Municipality/ ; ZYYZDXK-2023063//High-Level Traditional Chinese Medicine Key Discipline Construction Project of the National Administration of Traditional Chinese Medicine/ ; //Youth Talent Project of Longhua Hospital, affiliated with Shanghai University of Traditional Chinese Medicine/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Carcinoma, Hepatocellular/therapy/immunology/microbiology/metabolism/pathology ; *Liver Neoplasms/therapy/immunology/microbiology/metabolism/pathology ; *Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; }, abstract = {BACKGROUND: The relationship between hepatocellular carcinoma (HCC) and gut microbiota has gained attention for its impact on HCC immunotherapy.<br><br>METHODS: Key gut microbial metabolites, including bile acids, toll-like receptor 4, short-chain fatty acids, and bacterial toxins, contribute to HCC progression and influence immune responses through the gut-liver axis. As immune checkpoint inhibitors (ICIs) become common in HCC treatment, modulating the gut microbiota offers new strategies to enhance ICIs efficacy. However, individual differences in microbial composition introduce challenges, with some HCC patients showing resistance to ICIs.<br><br>RESULTS: This review summarizes the latest findings on the role of gut microbiota in HCC and explores emerging therapeutic approaches, including fecal microbiota transplantation, probiotics, antibiotics, and natural compounds.<br><br>CONCLUSIONS: The focus is on translating these insights into personalized medicine to optimize ICIs responses and improve HCC treatment outcomes.}, }
@article {pmid40313405, year = {2025}, author = {Zhao, H and Qiu, X and Wang, S and Wang, Y and Xie, L and Xia, X and Li, W}, title = {Multiple pathways through which the gut microbiota regulates neuronal mitochondria constitute another possible direction for depression.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1578155}, pmid = {40313405}, issn = {1664-302X}, abstract = {As a significant mental health disorder worldwide, the treatment of depression has long faced the challenges of a low treatment rate, significant drug side effects and a high relapse rate. Recent studies have revealed that the gut microbiota and neuronal mitochondrial dysfunction play central roles in the pathogenesis of depression: the gut microbiota influences the course of depression through multiple pathways, including immune regulation, HPA axis modulation and neurotransmitter metabolism. Mitochondrial function serves as a key hub that mediates mood disorders through mechanisms such as defective energy metabolism, impaired neuroplasticity and amplified neuroinflammation. Notably, a bidirectional regulatory network exists between the gut microbiota and mitochondria: the flora metabolite butyrate enhances mitochondrial biosynthesis through activation of the AMPK-PGC1α pathway, whereas reactive oxygen species produced by mitochondria counteract the flora composition by altering the intestinal epithelial microenvironment. In this study, we systematically revealed the potential pathways by which the gut microbiota improves neuronal mitochondrial function by regulating neurotransmitter synthesis, mitochondrial autophagy, and oxidative stress homeostasis and proposed the integration of probiotic supplementation, dietary fiber intervention, and fecal microbial transplantation to remodel the flora-mitochondrial axis, which provides a theoretical basis for the development of novel antidepressant therapies targeting gut-brain interactions.}, }
@article {pmid40312419, year = {2025}, author = {Cao, M and Deng, Y and Hao, Q and Yan, H and Wang, QL and Dong, C and Wu, J and He, Y and Huang, LB and Xia, X and Gao, Y and Chen, HN and Zhang, WH and Zhang, YJ and Zhuo, X and Dai, L and Hu, H and Peng, Y and Zhang, F and Liu, Z and Huang, W and Zhang, H and Yang, L and Shu, Y and Zhang, W and Zhang, Y and Xu, H}, title = {Single-cell transcriptomic analysis reveals gut microbiota-immunotherapy synergy through modulating tumor microenvironment.}, journal = {Signal transduction and targeted therapy}, volume = {10}, number = {1}, pages = {140}, pmid = {40312419}, issn = {2059-3635}, support = {82273445//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology/genetics/drug effects ; *Tumor Microenvironment/immunology/genetics/drug effects ; Mice ; *Single-Cell Analysis ; *Immunotherapy ; CD8-Positive T-Lymphocytes/immunology ; Humans ; Gene Expression Profiling ; Transcriptome ; *Neoplasms/immunology/genetics/therapy/microbiology ; *Immune Checkpoint Inhibitors/pharmacology ; Mice, Knockout ; Macrophages/immunology ; }, abstract = {The gut microbiota crucially regulates the efficacy of immune checkpoint inhibitor (ICI) based immunotherapy, but the underlying mechanisms remain unclear at the single-cell resolution. Using single-cell RNA sequencing and subsequent validations, we investigate gut microbiota-ICI synergy by profiling the tumor microenvironment (TME) and elucidating critical cellular interactions in mouse models. Our findings reveal that intact gut microbiota combined with ICIs may synergistically increase the proportions of CD8[+], CD4[+], and γδ T cells, reduce glycolysis metabolism, and reverse exhausted CD8[+] T cells into memory/effector CD8[+] T cells, enhancing antitumor response. This synergistic effect also induces macrophage reprogramming from M2 protumor Spp1[+] tumor-associated macrophages (TAMs) to Cd74[+] TAMs, which act as antigen-presenting cells (APCs). These macrophage subtypes show a negative correlation within tumors, particularly during fecal microbiota transplantation. Depleting Spp1[+] TAMs in Spp1 conditional knockout mice boosts ICI efficacy and T cell infiltration, regardless of gut microbiota status, suggesting a potential upstream role of the gut microbiota and highlighting the crucial negative impact of Spp1[+] TAMs during macrophage reprogramming on immunotherapy outcomes. Mechanistically, we propose a γδ T cell-APC-CD8[+] T cell axis, where gut microbiota and ICIs enhance Cd40lg expression on γδ T cells, activating Cd40 overexpressing APCs (e.g., Cd74[+] TAMs) through CD40-CD40L-related NF-κB signaling and boosting CD8[+] T cell responses via CD86-CD28 interactions. These findings highlight the potential importance of γδ T cells and SPP1-related macrophage reprogramming in activating CD8[+] T cells, as well as the synergistic effect of gut microbiota and ICIs in immunotherapy through modulating the TME.}, }
@article {pmid40311999, year = {2025}, author = {Liu, A and Wang, B and Wang, M and Tang, R and Xu, W and Xiao, W}, title = {L-theanine alleviates ulcerative colitis by repairing the intestinal barrier through regulating the gut microbiota and associated short-chain fatty acids.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {}, number = {}, pages = {115497}, doi = {10.1016/j.fct.2025.115497}, pmid = {40311999}, issn = {1873-6351}, abstract = {Ulcerative colitis (UC) is closely related to impaired intestinal barrier function and imbalanced gut microbial communities. L-theanine shows great potential in maintaining intestinal integrity and regulating the gut microbiota and associated short-chain fatty acids (SCFAs). However, whether L-theanine can alleviate UC by repairing the intestinal barrier through these regulatory processes remains unclear. In this study, L-theanine was used to optimize the gut microbiota, and the restorative effect and mechanism of L-theanine in UC by repairing the gut barrier through the gut microbiota and SCFAs were investigated via fecal microbiota transplantation. The findings revealed that L-theanine regulated the gut microbiota structure, increased SCFA contents, and promoted gut barrier repair in UC mice. Moreover, L-theanine upregulated the protein and mRNA expression of G-protein-coupled receptor 43 (GPR43), AKT, and phosphatidylinositide 3-kinase (PI3K). These results indicated that L-theanine alleviates UC by repairing the gut barrier via regulating the gut microbiota and SCFAs through the GPR43/PI3K/AKT signaling pathway activation. This study provides a method of preventing and treating UC via L-theanine as a safe food dietary supplement.}, }
@article {pmid40309228, year = {2025}, author = {Li, Y and Wu, YT and Wu, H}, title = {Management of hepatic encephalopathy following transjugular intrahepatic portosystemic shunts: Current strategies and future directions.}, journal = {World journal of gastroenterology}, volume = {31}, number = {15}, pages = {103512}, pmid = {40309228}, issn = {2219-2840}, mesh = {Humans ; *Portasystemic Shunt, Transjugular Intrahepatic/adverse effects ; *Hepatic Encephalopathy/etiology/therapy/prevention &amp; control/diagnosis ; *Hypertension, Portal/surgery/etiology ; *Liver Cirrhosis/complications/surgery ; *Postoperative Complications/therapy/etiology/prevention &amp; control ; Quality of Life ; Stents ; Treatment Outcome ; Biomarkers/blood ; Fecal Microbiota Transplantation ; }, abstract = {Transjugular intrahepatic portosystemic shunts (TIPSs) are generally used for the management of complications of portal hypertension in patients with decompensated cirrhosis. However, hepatic encephalopathy (HE), which impairs neuropsychiatric function and motor control, remains the primary adverse effect of TIPS, limiting its utility. Prompt prevention and treatment of post-TIPS HE are critical, as they are strongly associated with readmission rates and poor quality of life. This review focuses on the main pathophysiological mechanisms underlying post-TIPS HE, explores advanced biomarkers and predictive tools, and discusses current management strategies and future directions to prevent or reverse HE following TIPS. These strategies include preoperative patient assessment, individualized shunt diameter optimization, spontaneous portosystemic shunt embolization during the TIPS procedure, postoperative preventive and therapeutic measures such as nutrition management, medical therapy, fecal microbiota transplantation, and stent reduction.}, }
@article {pmid40309194, year = {2025}, author = {Tang, CT and Wu, Y and Tao, Q and Zeng, CY and Chen, YX}, title = {Thalidomide mitigates Crohn's disease colitis by modulating gut microbiota, metabolites, and regulatory T cell immunity.}, journal = {Journal of pharmaceutical analysis}, volume = {15}, number = {4}, pages = {101121}, pmid = {40309194}, issn = {2214-0883}, abstract = {Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3[+] (FOXP3[+]) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal B. fragilis was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3[+] Tregs and curbs pro-inflammatory pathways.}, }
@article {pmid40309103, year = {2025}, author = {Cong, X and Liu, X and Zhou, D and Xu, Y and Liu, J and Tong, F}, title = {Characterization and comparison of the fecal bacterial microbiota in Red Back Pine Root Snake (Oligodon formosanus) and Chinese Slug-Eating Snake (Pareas chinensis).}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1575405}, pmid = {40309103}, issn = {1664-302X}, abstract = {INTRODUCTION: The gastrointestinal tracts and oral cavities of animals harbor complex microbial communities that assist hosts in nutrient absorption and immune responses, thereby influencing behavior, development, reproduction, and overall health.<br><br>METHODS: We utilized metagenomic sequencing technology to conduct a detailed analysis of the fecal bacterial communities of six Red Back Pine Root Snakes (Oligodon formosanus, XT) and three Chinese Slug-Eating Snakes (Pareas chinensis, Z) individuals. The microbial composition was assessed through taxonomic profiling, alpha diversity analysis, and functional annotation using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.<br><br>RESULTS: The results indicated that Proteobacteria, Bacteroidetes, Firmicutes, Verrucomicrobia, Actinobacteria, and Fusobacteria were the dominant phyla in XT samples, while Z samples additionally contained Patescibacteria. Alpha diversity analysis revealed significant differences in species abundance at the family level, with Z samples exhibiting higher microbial richness than XT. Furthermore, KEGG analysis showed that XT had higher functional gene abundance in pathways related to transcription, translation, environmental adaptation, membrane transport, cellular communities (prokaryotes), motility, and replication/repair compared to Z.<br><br>DISCUSSION: This study provides a comparative analysis of their gut microbiomes, offering valuable insights for future research on zoonotic diseases, host-microbe interactions, and ecological, evolutionary, behavioral, and seasonal influences on snake microbiota. These findings contribute to a broader understanding of microbial ecology in reptiles and its implications for conservation and disease dynamics.}, }
@article {pmid40308808, year = {2025}, author = {Wei, H and Mai, ZL and Ma, BT and Chang, B}, title = {Creeping fat: A promising radiological predictor in small bowel Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {16}, pages = {105186}, pmid = {40308808}, issn = {2219-2840}, mesh = {Humans ; *Crohn Disease/diagnostic imaging/therapy/pathology ; *Intestine, Small/diagnostic imaging/pathology ; Treatment Outcome ; Fecal Microbiota Transplantation ; Predictive Value of Tests ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging ; *Adipose Tissue/diagnostic imaging/pathology ; Biological Products/therapeutic use ; }, abstract = {In this manuscript, we comment on the article by Hasnaoui et al. Specifically, we delve into the characteristic manifestation of Crohn's disease (CD) known as creeping fat (CF). Our primary focus is to investigate the potential of imaging features of CF in predicting the response of small bowel CD to biologic therapies and fecal microbiota transplantation. We believe that further research should be dedicated to developing methods for quantifying CF in order to provide more accurate predictive tools for the treatment of small bowel CD.}, }
@article {pmid40307551, year = {2025}, author = {Kennedy, MS and Freiburger, A and Cooper, M and Beilsmith, K and St George, ML and Kalski, M and Cham, C and Guzzetta, A and Ng, SC and Chan, FK and DeLeon, O and Rubin, D and Henry, CS and Bergelson, J and Chang, EB}, title = {Diet outperforms microbial transplant to drive microbiome recovery in mice.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {40307551}, issn = {1476-4687}, abstract = {A high-fat, low-fibre Western-style diet (WD) induces microbiome dysbiosis characterized by reduced taxonomic diversity and metabolic breadth[1,2], which in turn increases risk for a wide array of metabolic[3-5], immune[6] and systemic pathologies. Recent work has established that WD can impair microbiome resilience to acute perturbations such as antibiotic treatment[7,8], although little is known about the mechanism of impairment and the specific consequences for the host of prolonged post-antibiotic dysbiosis. Here we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) or WD, and find that only mice on RC undergo a rapid successional process of recovery. Metabolic modelling indicates that a RC diet promotes the development of syntrophic cross-feeding interactions, whereas in mice on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither. Furthermore, prolonged post-antibiotic dysbiosis in mice on WD renders them susceptible to infection by the intestinal pathogen Salmonella enterica serovar Typhimurium. Our data challenge widespread enthusiasm for faecal microbiota transplant (FMT) as a strategy to address dysbiosis, and demonstrate that specific dietary interventions are, at a minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural and less invasive alternative.}, }
@article {pmid40307477, year = {2025}, author = {Iyengar, A and Ramadass, B and Venkatesh, S and Mak, RH}, title = {Gut microbiota-targeted therapies in pediatric chronic kidney disease: gaps and opportunities.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {}, number = {}, pages = {}, pmid = {40307477}, issn = {1432-198X}, abstract = {Given the complex relationship between the gut microbiome and chronic kidney disease (CKD), exploring the potential role and scope of microbiota-targeted therapies in pediatric CKD is highly relevant. We aim to provide an overview of gut-targeted therapeutic strategies, including nutritional interventions (fiber, phytochemicals, fermented foods, and traditional Chinese medicines), probiotics, synbiotics, oral absorbents, and fecal microbial transplantation. Enhancing physical activity and preventing constipation are additional strategies that may promote gut microbiome health. In a uremic environment, gut microbiota-targeted therapies could potentially rebalance the gut microbiota, improve gut barrier function, decrease uremic toxin concentrations, enhance the production of short-chain fatty acids (SCFA), and reduce inflammation. While research in adult CKD patients has provided insights into these approaches, there are limited data in children with CKD. This review aims to summarize potential targeted therapies for restoring a balanced gut microbiota, emphasizing the need for studies that evaluate their effects on clinical outcomes in pediatric CKD.}, }
@article {pmid40306604, year = {2025}, author = {Lee, SH and Han, C and Shin, C}, title = {IUPHAR Review: Microbiota-Gut-Brain Axis and its role in Neuropsychiatric Disorders.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107749}, doi = {10.1016/j.phrs.2025.107749}, pmid = {40306604}, issn = {1096-1186}, abstract = {The human gut microbiome, composed of a vast array of microorganisms that have co-evolved with humans, is crucial for the development and function of brain systems. Research has consistently shown bidirectional communication between the gut and the brain through neuronal, endocrine, and immunological, and chemical pathways. Recent neuroscience studies have linked changes in the microbiome and microbial metabolites to various neuropsychiatric disorders such as autism, depression, anxiety, schizophrenia, eating disorders, and neurocognitive disorders. Novel metagenome-wide association studies have confirmed these microbiome variations in large samples and expanded our understanding of the interactions between human genes and the gut microbiome. The causal relationship between gut microbiota and neuropsychiatric disorders is being elucidated through the establishment of large cohort studies incorporating microbiome data and advanced statistical techniques. Ongoing animal and human studies focused on the microbiota-gut-brain axis are promising for developing new prevention and treatment strategies for neuropsychiatric conditions. The scope of these studies has broadened from microbiome-modulating therapies including prebiotics, probiotics, synbiotics and postbiotics to more extensive approaches such as fecal microbiota transplantation. Recent systematic reviews and meta-analyses have strengthened the evidence base for these innovative treatments. Despite extensive research over the past decade, many intriguing aspects still need to be elucidated regarding the role and therapeutic interventions of the microbiota-gut-brain axis in neuropsychiatric disorders.}, }
@article {pmid40306274, year = {2025}, author = {Kim, SH and White, Z and Gainullina, A and Kang, S and Kim, J and Dominguez, JR and Choi, Y and Cabrera, I and Plaster, M and Takahama, M and Czepielewski, RS and Yeom, J and Gunzer, M and Hay, N and David, O and Chevrier, N and Sano, T and Kim, KW}, title = {IL-10 sensing by lung interstitial macrophages prevents bacterial dysbiosis-driven pulmonary inflammation and maintains immune homeostasis.}, journal = {Immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.immuni.2025.04.004}, pmid = {40306274}, issn = {1097-4180}, abstract = {Crosstalk between the immune system and the microbiome is critical for maintaining immune homeostasis. Here, we examined this communication and the impact of immune-suppressive IL-10 signaling on pulmonary homeostasis. We found that IL-10 sensing by interstitial macrophages (IMs) is required to prevent spontaneous lung inflammation. Loss of IL-10 signaling in IMs initiated an inflammatory cascade through the activation of classical monocytes and CD4[+] T cell subsets, leading to chronic lung inflammation with age. Analyses of antibiotic-treated and germ-free mice established that lung inflammation in the animals lacking IL-10 signaling was triggered by commensal bacteria. 16S rRNA sequencing revealed Delftia acidovorans and Rhodococcus erythropolis as potential drivers of lung inflammation. Intranasal administration of these bacteria or transplantation of human fecal microbiota elicited lung inflammation in gnotobiotic Il10-deficient mice. These findings highlight that IL-10 sensing by IMs contributes to pulmonary homeostasis by preventing lung inflammation caused by commensal dysbiosis.}, }
@article {pmid40305972, year = {2025}, author = {Jiang, ZM and Fang, ZY and Yang, X and Ji, XX and Zhao, YY and Lin, BY and Weng, ZB and Liu, EH}, title = {Glycyrrhetinic acid ameliorates gastric mucosal injury by modulating gut microbiota and its metabolites via Thbs1/PI3K-Akt/p53 pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {142}, number = {}, pages = {156745}, doi = {10.1016/j.phymed.2025.156745}, pmid = {40305972}, issn = {1618-095X}, abstract = {BACKGROUND: Dysbiosis of the gut microbiota is pivotal in the development of gastric mucosa injury (GMI). Glycyrrhetinic acid (GA) is a bioactive triterpenoid compound abundantly present in licorice roots. Although GA's potential in mitigating GMI is recognized, its precise mechanism remains elusive, particularly concerning the role of gut microbiota.<br><br>PURPOSE: This study aimed to explore the protective effects and mechanisms of GA in preventing HCl/ethanol-induced GMI in rats.<br><br>RESULTS: This study demonstrated the protective effects of GA on gastric mucosa, evidenced by enhanced morphology and structure as revealed through H&amp;E staining. Utilizing fecal microbiota transplantation, GA was found to significantly mitigate oxidative damage, inflammation, and expression of apoptosis-related genes in GMI rats by a gut microbiota-dependent mechanism. 16S rRNA sequencing and metabolomics profiling revealed that GA ameliorated HCl/ethanol-triggered intestinal dysbiosis and imbalances in sphingolipid, arginine, and tryptophan metabolism. By promoting the prevalence of Bifidobacterium longum subsp. infantis (B. infantis) in the gut microbiota, GA improved metabolic disturbances linked to injury. Furthermore, its action mechanism was related to the inhibition of the Thbs1/PI3K-Akt/p53 signaling pathway.<br><br>CONCLUSION: The administration of GA improves GMI by mitigating intestinal dysbiosis and fostering colonization of B. infantis. GA offers therapeutic potential for GMI by modulating the Thbs1/PI3K-Akt/p53 pathway, thus alleviating inflammatory responses associated with gut microbiota imbalance.}, }
@article {pmid40305678, year = {2025}, author = {Wang, Y and Wang, X and Chen, Z and Zheng, J and Liu, X and Zheng, Y and Zheng, Z and Xu, Z and Zhang, Y and Chen, K and Zhang, Y and Yu, L and Ding, Y}, title = {Akkermansia muciniphila exacerbates acute radiation-induced intestinal injury by depleting mucin and enhancing inflammation.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wraf084}, pmid = {40305678}, issn = {1751-7370}, abstract = {Dysbiosis of gut microbiota plays a crucial role in acute radiation-induced intestinal injury. However, studies on the influence of gut microbiota on acute radiation-induced intestinal injury are inconsistent. In this study, we established an acute radiation-induced intestinal injury mouse model and performed fecal microbiota transplantation to explore the role of the gut microbiota in acute radiation-induced intestinal injury. We observed a significant increase in Akkermansia muciniphila following irradiation, whereas fecal microbiota transplantation effectively reduced Akkermansia muciniphila levels. Contrary to expectations, Akkermansia muciniphila supplementation increased acute radiation-induced intestinal injury and mortality. Mechanistically, post-radiation Akkermansia muciniphila upregulates mucin metabolism genes and consumes mucin, thinning the mucosal barrier and promoting the adhesion and translocation of potential pathogens to epithelial cells, thus exacerbating acute radiation-induced intestinal injury. This enables Akkermansia muciniphila to use mucin as an energy source. Additionally, Akkermansia muciniphila increases the inflammatory macrophage changes and secretion of inflammatory cytokines, leading to a decrease in epithelial stem cell density and inhibition of goblet cell differentiation, further exacerbating acute radiation-induced intestinal injury. Our findings suggest that in certain intestinal environments, the addition of Akkermansia muciniphila may worsen radiation-induced intestinal damage; thus, alternative approaches to reverse the dysbiosis associated with radiotherapy should be explored.}, }
@article {pmid40305219, year = {2025}, author = {Alves Costa Silva, C and Almonte, AA and Zitvogel, L}, title = {Oncobiomics: Leveraging Microbiome Translational Research in Immuno-Oncology for Clinical-Practice Changes.}, journal = {Biomolecules}, volume = {15}, number = {4}, pages = {}, pmid = {40305219}, issn = {2218-273X}, mesh = {Humans ; *Neoplasms/immunology/microbiology/therapy/metabolism ; *Translational Research, Biomedical ; *Microbiota ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/microbiology/immunology ; }, abstract = {Growing evidence suggests that cancer should not be viewed solely as a genetic disease but also as the result of functional defects in the metaorganism, including disturbances in the gut microbiota (i.e., gut dysbiosis). The human microbiota plays a critical role in regulating epithelial barrier function in the gut, airways, and skin, along with host metabolism and systemic immune responses against microbes and cancer. Collaborative international networks, such as ONCOBIOME, are essential in advancing research equity and building microbiome resources to identify and validate microbiota-related biomarkers and therapies. In this review, we explore the intricate relationship between the microbiome, metabolism, and cancer immunity, and we propose microbiota-based strategies to improve outcomes for individuals at risk of developing cancer or living with the disease.}, }
@article {pmid40304829, year = {2025}, author = {Alum, EU and Uti, DE and Ugwu, OP and Alum, BN and Edeh, FO and Ainebyoona, C}, title = {Unveiling the microbial orchestra: exploring the role of microbiota in cancer development and treatment.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {646}, pmid = {40304829}, issn = {2730-6011}, abstract = {The human microbiota comprises a diverse microbial ecosystem that significantly impacts health and disease. Among its components, the gut microbiota plays a crucial role in regulating metabolic, immunologic, and inflammatory responses. Dysbiosis, an imbalance in microbial composition, has been linked to carcinogenesis through mechanisms such as chronic inflammation, metabolic disturbances, epigenetic modifications, and immune system dysregulation. Additionally, dysbiosis influences the efficacy and toxicity of cancer therapies. Given these associations, there is growing interest in leveraging the microbiota as a biomarker for cancer detection and outcome prediction. Notably, distinct microbial signatures have been identified across various cancer types, suggesting their potential as diagnostic markers. Furthermore, modulation of the microbiota presents a promising avenue for improving cancer treatment outcomes through strategies such as antibiotics, prebiotics, probiotics, fecal microbiota transplantation, dietary interventions, small-molecule inhibitors, and phage therapy. To explore these relationships, we conducted a comprehensive literature review using Web of Science, Scopus, PubMed, MEDLINE, Embase, and Google Scholar as our primary online databases, focusing on indexed peer-reviewed articles up to the present year. This review aims to elucidate the role of dysbiosis in cancer development, examine the molecular mechanisms involved, and assess the impact of microbiota on cancer therapies. Additionally, we highlight microbiota-based therapeutic strategies and discuss their potential applications in cancer management. A deeper understanding of the intricate interplay between the microbiota and cancer may pave the way for novel approaches to cancer prevention, early detection, and treatment optimization.}, }
@article {pmid40302307, year = {2025}, author = {Hoffmann, DE and Javitt, GH and Kelly, CR and Keller, JJ and Baunwall, SMD and Hvas, CL}, title = {Fecal microbiota transplantation: a tale of two regulatory pathways.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2493901}, pmid = {40302307}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation/history/methods/standards/adverse effects ; Humans ; *Gastrointestinal Microbiome ; United States ; Europe ; }, abstract = {Fecal microbiota transplantation (FMT) is a procedure involving the transfer of intestinal microbiota from a healthy donor to a patient to restore a functional intestinal microbiome. First described in modern science in 1958, the use of FMT has been practiced for decades, but only during the past dozen years have clinical frameworks and legal regulations from competent authorities been developed. Future development of microbiota-derived medical therapies will be shaped by the regulatory frameworks of various jurisdictions. This review examines the historical development and status of FMT regulations in the United States and Europe, with particular attention to their respective approaches to ensuring the safety and quality of the therapeutic product and patient access.}, }
@article {pmid40301246, year = {2025}, author = {Liu, X and Cui, J and Tan, X and Yu, Y and Niu, J and Wang, Q}, title = {Short-Chain Fatty Acids Alleviate Perioperative Neurocognitive Disorders Through BDNF/PI3K/Akt Pathway in Middle-Aged Rats.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40301246}, issn = {1559-1182}, support = {246Z7702G//Central Government - Guided Local Science and Technology Development Fund/ ; }, abstract = {Perioperative neurocognitive disorders (PND), characterized by persistent cognitive impairment lasting from days to years, present substantial clinical challenges in elderly surgical populations, profoundly compromising functional independence, quality of life, and long-term prognosis. We aimed to investigate the effects of short-chain fatty acids (SCFAs) treatment on PND via mediating Brain-derived neurotrophic factor (BDNF)/Phosphatidylinositol3-kinase (PI3K)/Protein kinase B (Akt) pathway. Using 16S rDNA sequencing targeting the V3-V4 hypervariable regions, we first demonstrated significant gut microbiota dysbiosis in PND model rats, accompanied by altered SCFAs profiles. Subsequent fecal microbiota transplantation (FMT) experiments established causal relationships between PND-associated microbial alterations and spatial cognitive deficits. Mechanistically, SCFAs supplementation attenuated neuronal damage and restored synaptic plasticity, as evidenced by Nissl staining quantification (reduced chromatolysis), TUNEL assay (decreased apoptosis rate), and immunohistochemical analysis (upregulated NeuN expression). Molecular investigations revealed that SCFAs-mediated cognitive improvement involved BDNF upregulation and subsequent PI3K/Akt pathway activation, ultimately enhancing neuronal survival and synaptic integrity. Notably, PND animals exhibited characteristic neuropathological features including synaptic density reduction (PSD-95 downregulation), neuroinflammation amplification (IL-6 elevation), and apoptosis activation-all significantly reversed by SCFA intervention. Our findings establish a novel gut-brain axis mechanism wherein microbiota-derived SCFAs may exert neuroprotection through BDNF-dependent PI3K/Akt signaling, and offer potential therapeutic strategies for PND management.}, }
@article {pmid40301116, year = {2025}, author = {Kamath, S and Bryant, RV and Costello, SP and Day, AS and Forbes, B and Haifer, C and Hold, G and Kelly, CR and Li, A and Pakuwal, E and Stringer, A and Tucker, EC and Wardill, HR and Joyce, P}, title = {Translational strategies for oral delivery of faecal microbiota transplantation.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-335077}, pmid = {40301116}, issn = {1468-3288}, abstract = {Faecal microbiota transplantation (FMT) has emerged as a transformative therapy for Clostridioides difficile infections and shows promise for various GI and systemic diseases. However, the poor patient acceptability and accessibility of 'conventional' FMT, typically administered via colonoscopies or enemas, hinders its widespread clinical adoption, particularly for chronic conditions. Oral administration of FMT (OralFMT) overcomes these limitations, yet faces distinct challenges, including a significant capsule burden, palatability concerns and poor microbial viability during gastric transit. This review provides a comprehensive analysis of emerging strategies that aim to advance OralFMT by: (1) refining processing technologies (eg, lyophilisation) that enable manufacturing of low-volume FMT formulations for reducing capsule burden and (2) developing delivery technologies that improve organoleptic acceptability and safeguard the microbiota for targeted colonic release. These advancements present opportunities for OralFMT to expand its therapeutic scope, beyond C. difficile infections, towards chronic GI conditions requiring frequent dosing regimens. While this review primarily focuses on optimising OralFMT delivery, it is important to contextualise these advancements within the broader shift towards defined microbial consortia. Live biotherapeutic products (LBPs) offer an alternative approach, yet the interplay between OralFMT and LBPs in clinical practice remains unresolved. We postulate that continued innovation in OralFMT and LBPs via a multidisciplinary approach can further increase therapeutic efficacy and scalability by enabling disease site targeting, co-delivery of therapeutic compounds and overcoming colonisation resistance. Realising these goals positions OralFMT as a cornerstone of personalised care across a range of diseases rooted in microbiome health.}, }
@article {pmid40300858, year = {2025}, author = {Almonte, AA and Zitvogel, L}, title = {Gut reactions: harnessing microbial metabolism to fuel next-generation cancer immunotherapy.}, journal = {Journal for immunotherapy of cancer}, volume = {13}, number = {4}, pages = {}, pmid = {40300858}, issn = {2051-1426}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology ; }, abstract = {Immunotherapies, including immune checkpoint inhibitors and chimeric antigen receptor-T cell therapies, depend heavily on a healthy and diverse gut microbiome for optimal efficacy. Dysbiosis, or an imbalance in gut microbial composition and function, can diminish immunotherapy responses by altering immune cell trafficking and metabolic output. Key microbial metabolites such as short-chain fatty acids and modified bile acids shape host immunity and influence T-cell function, while their disruption can foster an immunosuppressive microenvironment. Emerging strategies to restore a balanced microbiome and boost treatment outcomes include dietary interventions, supplementation with beneficial microbes, and fecal microbiota transplantation. Despite these advances, challenges remain in defining dysbiosis, identifying reliable biomarkers, and tailoring microbiota-centered interventions. Nevertheless, as our understanding evolves, the gut microbiome holds promise as an integral component of personalized cancer immunotherapy.}, }
@article {pmid40300731, year = {2025}, author = {Mahmoud, AA and Wang, X and Liao, X and Zhang, S and Ding, T and Ahn, J}, title = {Impact of prophages on gut microbiota and disease associations.}, journal = {Microbial pathogenesis}, volume = {204}, number = {}, pages = {107642}, doi = {10.1016/j.micpath.2025.107642}, pmid = {40300731}, issn = {1096-1208}, abstract = {The gut microbiota plays an important role in maintaining host health by affecting various physiological functions. Among the diverse microbial communities in the gut, prophages are integral components of bacterial genomes, contributing significantly to bacterial evolution, ecology and pathogenicity. Prophages are capable of switching to lytic cycles in response to various internal and external factors. Factors that induce prophage induction include DNA damage, oxidative stress, nutrient availability, host immune response, quorum sensing, diet, secondary metabolites, antibiotics, and lifestyle changes. Prophage induction could contribute to both gut homeostasis and dysbiosis. Importantly, the connections between prophage induction and disorders such as inflammatory bowel disease, ulcerative colitis, and bacterial vaginosis highlight the dual roles of prophages in both health and disease. Although therapeutic approaches such as phage therapy (PT), fecal microbiota transplants (FMT), and fecal virome transplants (FVT) have gained attention, the concept of dietary prophage induction therapy offers a novel, targeted method to modulate gut microbiota. In spite of recent advances in understanding the role of prophages in gut health, the exact mechanisms by which they influence gut health remain only partially understood. Therefore, further research is needed to elucidate additional molecular mechanisms of prophage induction pathways and to explore their implications for gut microbiota dynamics and disease associations. This review discusses the molecular mechanisms and key factors that trigger prophage induction in the gut. Insights into these processes could lead to innovative therapeutic strategies that utilize prophages to support gut health.}, }
@article {pmid40300372, year = {2025}, author = {Liu, Z and Zhang, H and Wang, J and Yao, Y and Wang, X and Liu, Y and Fang, W and Liu, X and Zheng, Y}, title = {Clca1 deficiency exacerbates colitis susceptibility via impairment of mucus barrier integrity and gut microbiota homeostasis.}, journal = {Microbiological research}, volume = {297}, number = {}, pages = {128191}, doi = {10.1016/j.micres.2025.128191}, pmid = {40300372}, issn = {1618-0623}, abstract = {The intestinal mucus barrier has emerged as a promising therapeutic target for inflammatory bowel disease. Understanding its regulatory mechanisms is critical for elucidating ulcerative colitis (UC) pathogenesis, improving diagnostics, guiding treatments, and preventing relapse. Chloride Channel Accessory 1 (Clca1), a constituent of the mucus layer, remains understudied in colitis. Here, we investigated Clca1's role in mucosal immunity and intestinal homeostasis using experimental colitis models. Clca1-deficient (Clca1[-/-]) mice displayed compromised mucus layer integrity, reduced neutrophil infiltration, and gut microbiota dysbiosis. Notably, Clca1[-/-] mice exhibited exacerbated colitis severity following dextran sulfate sodium (DSS) challenge, accompanied by a diminished goblet cell populations. Fecal microbiota transplantation (FMT) studies revealed that gut microbiota critically modulates divergent phenotypic outcomes between genotypes. Our findings establish Clca1 as a multifunctional regulator of mucus barrier integrity through mechanisms involving goblet cell maintenance, neutrophil-mediated immunity, and host-microbiota crosstalk. These results advance the understanding of UC pathogenesis and identify Clca1-associated pathways as potential targets for barrier restoration therapies.}, }
@article {pmid40299998, year = {2025}, author = {Cao, J and Wang, X and Lei, Y and Jiang, X and Kannan, K and Li, M}, title = {Health Risks of Low-Dose Dietary Exposure to Triphenyl Phosphate and Diphenyl Phosphate in Mice: Insights from the Gut-Liver Axis.}, journal = {Environmental science &amp; technology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.est.4c08270}, pmid = {40299998}, issn = {1520-5851}, abstract = {Aryl phosphate esters have been detected throughout the natural environment and in human blood samples, making it important to determine the health risks associated with exposure to triphenyl phosphate (TPHP) and its metabolite diphenyl phosphate (DPHP). Here, C57BL/6J male mice were exposed to TPHP or DPHP for 12 weeks at estimated daily intake doses of 0.1 and 7 μg/kg bw/day. TPHP intake affected the levels of short-chain fatty acids and bile acids in the gut, enhancing the production of 29 medium- and long-chain fatty acids in the liver by 3.72-fold and significantly increasing hepatic lipid and cholesterol levels. Metabolomic and molecular analysis confirmed that elevated liver cholesterol levels persisted after an 8 week recovery period. Gut microbiota-dependent cholesterol alterations were the toxic end points observed in TPHP-fed mice, as supported by the results of fecal microbiota transplantation. In DPHP-fed mice, serotonergic and glutamatergic synapses were simultaneously altered in the liver and intestine, corresponding to the reduction of five brain neurotransmitters (15.4-60.8%). Decreased liver carbohydrate levels and insulin resistance were observed in the DPHP-fed mice. These results suggest that TPHP and DPHP affect metabolism via different toxic modes, mediated through the gut-liver axis, providing novel insights into the mechanisms of organophosphate-ester-mediated metabolic disruption.}, }
@article {pmid40299512, year = {2025}, author = {Eslami, M and Adampour, Z and Fadaee Dowlat, B and Yaghmayee, S and Motallebi Tabaei, F and Oksenych, V and Naderian, R}, title = {A Novel Frontier in Gut-Brain Axis Research: The Transplantation of Fecal Microbiota in Neurodegenerative Disorders.}, journal = {Biomedicines}, volume = {13}, number = {4}, pages = {}, pmid = {40299512}, issn = {2227-9059}, abstract = {The gut-brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut-brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy.}, }
@article {pmid40299326, year = {2025}, author = {Hauser, G and Benjak Horvat, I and Rajilić-Stojanović, M and Krznarić-Zrnić, I and Kukla, M and Aljinović-Vučić, V and Mikolašević, I}, title = {Intestinal Microbiota Modulation by Fecal Microbiota Transplantation in Nonalcoholic Fatty Liver Disease.}, journal = {Biomedicines}, volume = {13}, number = {4}, pages = {}, pmid = {40299326}, issn = {2227-9059}, abstract = {Numerous factors are involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which are responsible for its development and progression as an independent entity, but also thanks to their simultaneous action. This is explained by the hypothesis of multiple parallel hits. These factors are insulin resistance, lipid metabolism alteration, oxidative stress, endoplasmic reticulum stress, inflammatory cytokine liberation, gut microbiota dysbiosis or gut-liver axis activation. This is a systematic review which has an aim to show the connection between intestinal microbiota and the role of its disbalance in the development of NAFLD. The gut microbiota is made from a wide spectrum of microorganisms that has a systemic impact on human health, with a well-documented role in digestion, energy metabolism, the stimulation of the immune system, synthesis of essential nutrients, etc. It has been shown that dysbiosis is associated with all three stages of chronic liver disease. Thus, the modulation of the gut microbiota has attracted research interest as a novel therapeutic approach for the management of NAFLD patients. The modification of microbiota can be achieved by substantial diet modification and the application of probiotics or prebiotics, while the most radical effects are observed by fecal microbiota transplantation (FMT). Given the results of FMT in the context of metabolic syndrome (MetS) and NAFLD in animal models and scarce pilot studies on humans, FMT seems to be a promising treatment option that could reverse intestinal dysbiosis and thereby influence the course of NAFLD.}, }
@article {pmid40298931, year = {2025}, author = {Gao, X and Fu, N and Ben, Q and Bu, X}, title = {A Meta-Analysis of the Effects of Gut Microbiota-Based Interventions on Gastrointestinal and Behavioral Symptoms in Children With Autism Spectrum Disorder.}, journal = {Nutrition reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/nutrit/nuaf050}, pmid = {40298931}, issn = {1753-4887}, abstract = {CONTEXT: Despite an increasing body of research showing gut microbiota-based interventions can improve gastrointestinal (GI) symptoms and behavioral symptoms in both humans and animals, there are still disagreements about its impact on autism spectrum disorder (ASD) in children.<br><br>OBJECTIVE: The goal of this systematic review and meta-analysis was to fully investigate the effects of gut microbiota-based interventions (eg, fecal microbiota transplantation, probiotics, prebiotics) on GI and behavioral symptoms in children with ASD.<br><br>DATA SOURCES: The PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, and Scopus databases were searched from inception to August 25, 2024.<br><br>DATA EXTRACTION: Data were extracted by 2 reviewers independently, and discrepancies in authors' judgments were resolved by discussion or consulting a third author.<br><br>DATA ANALYSIS: The scale score of GI and behavioral symptoms before and after the intervention was extracted from included trials to evaluate the therapeutic effects of gut microbiota-based therapy in children with autism.<br><br>RESULTS: A total of 5722 records were identified, of which 13 included in narrative synthesis and 8 studies included a meta-analysis. The nonsignificant overall effect size of gut microbiota-based intervention on GI symptoms (standardized mean difference [SMD] = -0.34 [95% CI, -0.76 to 0.07]; P&#x2009;=&#x2009;.11) and behavioral symptoms (SMD&#x2009;=&#x2009;-0.18 [95% CI, -0.37 to 0.02]; P&#x2009;=&#x2009;.08) was observed. Nevertheless, we observed a significant effect size on behavioral symptoms in the subgroup of the intervention duration (SMD&#x2009;=&#x2009;-0.26 [95% CI, -0.49 to -0.03]; P&#x2009;=&#x2009;.02).<br><br>CONCLUSIONS: In children with autism, the proof supporting the validity of gut microbiota-based intervention on GI and behavioral symptoms should be interpreted cautiously. More randomized controlled trials with rigorous methodological quality are required to precisely confirm the curative benefits of gut microbiota-based interventions on GI and behavioral symptoms in children with autism.<br><br>PROSPERO registration no. CRD42024583213.}, }
@article {pmid40298495, year = {2025}, author = {Cusumano, G and Flores, GA and Venanzoni, R and Angelini, P}, title = {The Impact of Antibiotic Therapy on Intestinal Microbiota: Dysbiosis, Antibiotic Resistance, and Restoration Strategies.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {40298495}, issn = {2079-6382}, abstract = {The human gut microbiota-an intricate and dynamic ecosystem-plays a pivotal role in metabolic regulation, immune modulation, and the maintenance of intestinal barrier integrity. Although antibiotic therapy is indispensable for managing bacterial infections, it profoundly disrupts gut microbial communities. Such dysbiosis is typified by diminished diversity and shifts in community structure, especially among beneficial bacterial genera (e.g., Bifidobacterium and Eubacterium), and fosters antibiotic-resistant strains and the horizontal transfer of resistance genes. These alterations compromise colonization resistance, increase intestinal permeability, and amplify susceptibility to opportunistic pathogens like Clostridioides difficile. Beyond gastrointestinal disorders, emerging evidence associates dysbiosis with systemic conditions, including chronic inflammation, metabolic syndrome, and neurodegenerative diseases, underscoring the relevance of the microbiota-gut-brain axis. The recovery of pre-existing gut communities post-antibiotic therapy is highly variable, influenced by drug spectrum, dosage, and treatment duration. Innovative interventions-such as fecal microbiota transplantation (FMT), probiotics, synbiotics, and precision microbiome therapeutics-have shown promise in counteracting dysbiosis and mitigating its adverse effects. These therapies align closely with antibiotic stewardship programs aimed at minimizing unnecessary antibiotic use to preserve microbial diversity and curtail the spread of multidrug-resistant organisms. This review emphasizes the pressing need for microbiota-centered strategies to optimize antibiotic administration, promote long-term health resilience, and alleviate the disease burden associated with antibiotic-induced dysbiosis.}, }
@article {pmid40297591, year = {2025}, author = {Pei, X and Liu, L and Han, Y}, title = {Advances in human microbiome and prostate cancer research.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1576679}, pmid = {40297591}, issn = {1664-3224}, mesh = {Humans ; *Prostatic Neoplasms/microbiology/therapy/immunology/metabolism/etiology ; Male ; *Microbiota ; *Gastrointestinal Microbiome ; Tumor Microenvironment/immunology ; Animals ; }, abstract = {Prostate cancer (PCa) is the second most common malignant tumor in men worldwide, and its metastatic and heterogeneous nature makes it significantly more difficult to treat. Recent studies have revealed the critical role of microbiota in PCa occurrence, progression, and treatment. Accumulating evidence from 16S rRNA and metagenomic sequencing suggests the presence of specific microbiota in prostate tissues and macrogenomics techniques: cancerous tissues are enriched with pro-inflammatory genera (e.g., Fusobacterium, Propionibacterium acnes), whereas commensal bacteria (e.g., Pseudomonas) are more common in paracancerous tissues. The microbiota drive tumor progression through activation of the NF-κB/STAT3 pathway to induce chronic inflammation, modulation of the immune microenvironment (e.g., Treg/Th17 imbalance and M2-type macrophage polarization), and metabolite (e.g., LPS, short-chain fatty acids)-mediated hormonal and epigenetic regulation. In terms of clinical translation, urinary microbiota characterization combined with metabolomics analysis may enhance diagnostic specificity, while gut flora modulation (e.g., probiotic interventions or fecal transplants) may improve resistance to androgen deprivation therapy. Current challenges include sequencing accuracy of low-biomass samples, limitations of causal mechanism validation models, and large cohort heterogeneity. In the future, it will be necessary to integrate multi-omics technologies to explore the bidirectional regulation of the "gut-prostate axis" and develop personalized therapeutic strategies targeting microorganisms. In this paper, we systematically review the interactions between microbiota and PCa and their clinical potentials to provide a theoretical basis for precision diagnosis and treatment.}, }
@article {pmid40297203, year = {2025}, author = {Nguyen, JDK and Yohannes, KG and Setiady, I and Phillips, EC and Hays, RA and Behm, BW and Warren, CA and Shin, JH}, title = {Factors associated with failure of fecal microbiota transplant for recurrent Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251334517}, pmid = {40297203}, issn = {1756-283X}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) has emerged as a prevalent and recurrent antibiotic-associated infection. Fecal microbiota transplantation (FMT) is the most effective treatment for recurrent CDI (rCDI). Despite high success rates, FMT is ineffective in 5%-20% of cases. Factors associated with failure have not been clearly defined.<br><br>OBJECTIVES: In this study, we seek to identify factors predictive of FMT failure.<br><br>DESIGN: Retrospective cohort study.<br><br>METHODS: A retrospective chart review was conducted on adult patients who were screened at the Complicated C. difficile Clinic at the University of Virginia Health System and received FMT for rCDI between 2013 and 2022. The primary outcome was failure of FMT, defined as either rCDI or all-cause death within 1&#x2009;year.<br><br>RESULTS: In total, 240 patients underwent FMT: 70.4% were female, the median age was 68, and the median episode of CDI was 4. A total of 24.6% experienced failure within 1&#x2009;year (18.3% had rCDI and 7.1% died). Age 70 or older (odds ratio (OR)&#x2009;=&#x2009;2.66 (1.29-5.67)), &#x2a7e;4 episodes of CDI (OR&#x2009;=&#x2009;3.13 (1.47-7.09)), and diabetes mellitus (OR&#x2009;=&#x2009;2.82 (1.25-6.50)) were associated with failure on multivariate analysis.<br><br>CONCLUSION: Our study shows that FMT remains an effective treatment for rCDI. We highlight several factors associated with FMT failure, such as older age, &#x2a7e;4 episodes of CDI, and diabetes mellitus, and the need for additional research to clearly define causality.}, }
@article {pmid40296251, year = {2025}, author = {Zheng, H and Chen, Y and Lu, S and Liu, Z and Ma, Y and Zhang, C and Zhang, Y and Zhang, J and Liu, C and Chu, M and Pei, F and Liu, S and Duan, L}, title = {Mechanosensory Piezo2 regulated by gut microbiota participates in the development of visceral hypersensitivity and intestinal dysmotility.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2497399}, pmid = {40296251}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Humans ; Mice ; *Irritable Bowel Syndrome/microbiology/physiopathology/metabolism/therapy ; *Ion Channels/metabolism/genetics ; Male ; Female ; Fecal Microbiota Transplantation ; *Gastrointestinal Motility ; Adult ; Middle Aged ; Colon/metabolism ; Mice, Inbred C57BL ; Feces/microbiology ; Fusobacterium/physiology ; Dysbiosis/microbiology ; Disease Models, Animal ; Ganglia, Spinal/metabolism ; Akkermansia ; }, abstract = {The gut microbiota plays a crucial role in the manifestation of intestinal dysfunction associated with irritable bowel syndrome (IBS). The mechanosensory Piezo2 has been implicated in the regulation of intestinal function. However, it remains unclear whether Piezo2 is modulated by the gut microbiota, thus contributing to the development of visceral hypersensitivity and gut dysmotility. The study enrolled patients with diarrhea-predominant IBS (IBS-D) alongside healthy controls (HC). Questionnaires, rectal barostat test, and colonoscopy with mucosal biopsy were conducted. Fecal microbiota transplantation (FMT) was performed using samples from HC or IBS-D patients, and interventions with Akkermansia muciniphila or Fusobacterium varium were carried out on colon- or dorsal root ganglion (DRG)- Piezo2 knockdown pseudo-germ-free mice. Visceral sensitivity and intestinal motility were assessed. Piezo2 levels were detected using western blot and immunofluorescence. Fecal 16S rRNA sequencing and cecum untargeted metabolomics analysis, followed by molecular docking predictions of Piezo2, were also performed. The ratio of Piezo2[+]/5-HT[+] cells was lower in IBS-D patients, positively correlated with visceral sensation and intestinal dysbiosis. The mice that received FMT from IBS-D patients exhibited colonic dysmotility and visceral hypersensitivity, along with elevated Piezo2 protein levels in the colon and DRG. Knockdown of Piezo2 in the colon or DRG ameliorated the FMT-induced colonic dysmotility and visceral hypersensitivity. Fecal 16S rRNA sequencing revealed distinct microbiota composition. Notably, Fusobacterium varium, but not Akkermansia muciniphila, induced gut dysmotility and visceral hypersensitivity, effects that could be alleviated by colon or DRG Piezo2 knockdown. Additionally, Fusobacterium varium lead to increased Piezo2 protein levels, as well as elevated levels of indole-3-acetic acid and indole-3-acrylic acid, which were predicted to bind to Piezo2, causing disturbances. Piezo2 can be regulated by gut microbiota and involved in visceral hypersensitivity and colonic dysmotility, with Fusobacterium varium playing a crucial role.}, }
@article {pmid40295906, year = {2025}, author = {Ahmadi, A and Shokoohizadeh, L and Sheikhesmaili, F and Mirzaei, MK and Mohammadi, A and Nikkhoo, B and Khodaei, H and Alikhani, MY and Yousefimashouf, R}, title = {Gut microbiomes and treatment-resistant ulcerative colitis: a case-control study using qPCR.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {254}, pmid = {40295906}, issn = {1471-2180}, mesh = {Humans ; *Colitis, Ulcerative/microbiology/drug therapy ; Case-Control Studies ; *Gastrointestinal Microbiome/genetics ; Male ; Adult ; Female ; Feces/microbiology ; Middle Aged ; Real-Time Polymerase Chain Reaction ; *Bacteria/genetics/classification/isolation &amp; purification ; Young Adult ; }, abstract = {BACKGROUND: The gut microbiome has been identified as a pivotal factor in ulcerative colitis (UC), given its role as the main reservoir of microbes in the body. This community of microorganisms, present in variable concentrations in the digestive tract, makes a wide range of beneficial roles for the host. However, the role of the gut microbiome in patients with refractory UC is still significant, so this study aimed to further investigate the role of these bacteria in patients with refractory UC.<br><br>METHODS: This case-control study was conducted on stool samples from four distinct groups: the first group comprised new patients diagnosed with ulcerative colitis (all of them had responded to treatment after follow-up) (N&#x2009;=&#x2009;24); the second group consisted of patients with treatment-resistant ulcerative colitis (N&#x2009;=&#x2009;23); the third group included first-degree relatives of group 1 patients (N&#x2009;=&#x2009;24); and the fourth group consisted of first-degree relatives of group 2 patients (N&#x2009;=&#x2009;23). The research tools employed in this study included a questionnaire, quantitative real-time PCR (qPCR) test, and culture on stool samples.<br><br>RESULT: The mean age of patients in groups 1 and 2 was 45.88&#x2009;&#xb1;&#x2009;18.51 and 41.30&#x2009;&#xb1;&#x2009;13.01 years, while the mean age of controls in groups 3 and 4 was 37.29&#x2009;&#xb1;&#x2009;9.62 and 40.96&#x2009;&#xb1;&#x2009;13.01 years, respectively. Stool culture results for pathogenic bacteria were negative in all four groups. The of history of consuming dairy products containing probiotics was highest in Group 1, with 22 (91.67%) subjects, while the lowest was observed in Group 3, with 16 (66.67%). The highest history of self-administered antibiotic use was observed in Group 2, with 13 cases (56.52%), while the lowest was noted in Group 3, with 4 cases (16.67%). The findings indicated a statistically significant relationship (P&#x2009;<&#x2009;0.05) between Groups 2 and 4 with respect to the E. coli and Bifidobacterium ssp. microbial population. Additionally, a significant relationship was identified between the Lactobacillus ssp., Bifidobacterium ssp., and Bacteroides ssp. microbial community between groups 1 and 2 (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: The findings of this study demonstrated that several intestinal microbiomes have a substantial impact on the management of ulcerative colitis. The results of this study suggest that by comparing the gut microbiome of treatment-resistant and individuals newly diagnosed with ulcerative colitis, we can gain a better understanding of microbiome differences that may influence treatment outcomes. The results of this study may also lead to the identification of new therapeutic strategies that are based on regulating the gut microbiome. These strategies could include the use of fecal microbiome transplantation (FMT), probiotics, prebiotics, or specific bacteria-based therapies.}, }
@article {pmid40295607, year = {2025}, author = {Mohammadi, M and Rahimi, K and Rezaie, A and Tabandeh, MR}, title = {The role of fecal microbiota transplantation on the NLRP3-Caspase 1 pathway and anxiety like behavioral in the ulcerative colitis model in rats.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {14831}, pmid = {40295607}, issn = {2045-2322}, mesh = {Animals ; *Caspase 1/metabolism/genetics ; *Fecal Microbiota Transplantation/methods ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Anxiety/therapy/metabolism/etiology ; Rats ; Signal Transduction ; Male ; *Colitis, Ulcerative/therapy/chemically induced/metabolism ; Disease Models, Animal ; Hippocampus/metabolism ; Behavior, Animal ; Colon/metabolism/pathology ; Acetic Acid ; Interleukin-18/metabolism ; }, abstract = {The purpose of this study was to investigate the function of the NLRP3-Caspase 1 signaling pathway in the colon during fecal microbiota transplantation (FMT) in colitis induced by acetic acid. Additionally, the study aimed to determine the impact of FMT on anxiety behaviors by analyzing the function of the NLRP3-Caspase 1 signaling pathway in the hippocampus. A total of twenty-four rats were selected randomly for the study and divided into two groups, a control group, and an acid acetic-induced colitis group. The acid acetic-induced colitis group further consisted of three subgroups: untreated acid acetic-induced colitis group, mesalazine 0.3 gr/kg group, and FMT group. After 6 days, the colon was evaluated for macroscopic and microscopic damage, and the signaling pathway NLRP3-Caspase1-related genes in the colon and hippocampus were analyzed. Additionally, anxiety-related behaviors of the rats were observed. FMT decreased colonic mRNA expression levels of NLRP3, NF-кB, and Caspase1 and pro-inflammatory cytokines (IL-1β and IL-18). Also, FMT reduced the expression of NLRP3, NF-κB, and Caspase1 protein levels as well as pro-inflammatory cytokines IL-1β and IL-18 in the hippocampus, resulting in a reduction of anxiety behaviors in the open field and elevated plus maze tests in the colitis model. FMT may improve acetic acid-induced colitis by regulating the NLRP3-Caspase1 signaling pathway in the colon. It also reduced colitis-induced anxiety behavior by regulating the expression of proteins related to the NLRP3-Caspase 1 pathway in the hippocampus.}, }
@article {pmid40295196, year = {2025}, author = {Sun, J and Shi, L and Xu, F and Sun, H and Liu, Y and Sun, J and Zhou, Q}, title = {Naringenin Inhibits Colorectal Cancer associated with a High-Fat Diet through Modulation of Gut Microbiota and IL-6/STAT3 Pathway.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2412029}, doi = {10.4014/jmb.2412.12029}, pmid = {40295196}, issn = {1738-8872}, mesh = {*Flavanones/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Colorectal Neoplasms/drug therapy/microbiology/prevention &amp; control/etiology/metabolism ; *STAT3 Transcription Factor/metabolism ; *Diet, High-Fat/adverse effects ; Animals ; *Interleukin-6/metabolism ; Mice ; Male ; Signal Transduction/drug effects ; Fecal Microbiota Transplantation ; Humans ; Mice, Inbred C57BL ; Bacteria/drug effects/classification/genetics ; }, abstract = {Colorectal cancer (CRC) is a worldwide health issue. It causes illness and death in millions of people each year. A positive correlation has been observed between the intake of dietary fat and the development of CRC. The composition of gut microbiota exhibits a significant correlation with pathophysiologic processes in intestine. Clinical treatment remains inadequate due to the complex pathogenic mechanisms of CRC triggered by a high-fat diet (HFD). Naringenin, a flavonoid from grapefruit, has anti-cancer activity. Our findings suggest that naringenin enhances gut microbiota diversity by increasing the abundance of beneficial bacterial species while reducing opportunistic pathogenic bacteria. The fecal microbiota transplantation assay (FMT) demonstrated that the anti-HFD-CRC activity of naringenin depended on the gut microbiota. Furthermore, naringenin antagonized the IL-6/STAT3 pathway. These results suggest that naringenin may be a potential treatment for HFD-CRC.}, }
@article {pmid40294087, year = {2025}, author = {Duarte, L and Magne, F and Gotteland, M}, title = {Gut microbiota in patients with metabolic, dysfunction-associated steatotic liver disease.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {}, number = {}, pages = {}, pmid = {40294087}, issn = {1473-6519}, abstract = {PURPOSE OF REVIEW: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent condition that can progress to fibrosis, steatohepatitis, and hepatocellular carcinoma. This review examines recent advances concerning the role of gut microbiota in MASLD and microbiota-focused interventions to positively impact disease outcome.<br><br>RECENT FINDINGS: Dysbiotic microbiota and a compromised gut barrier facilitate the translocation of microbial-associated molecular patterns and harmful metabolites into the portal circulation and liver, where they exacerbate inflammatory and fibrogenic processes. Conversely, other bacterial metabolites have protective effects in the liver. Therefore, microbiota homeostasis is essential for maintaining liver health.<br><br>SUMMARY: Levels of harmful bacterial metabolites including ethanol, NH3, trimethylamine-L-oxide, 2-oleylglycerol, and litocholic acid are often increased in patients with MASLD. Conversely, short-chain fatty acids, indole derivatives, histidine, and the acids taurodeoxycholic, 3-succinylcholic, and hyodeoxycholic are decreased. The main aim of current interventions/treatments is to reduce harmful metabolites and increase beneficial ones. These interventions include drugs (pemafibrate, metformin, obeticholic acid), natural compounds (silymarin, lupeol, dietary fiber, peptides), exogenous bacteria (probiotics, gut symbionts), special diets (Mediterranean diet, time-restricted feeding), as well as microbiota transplantation, and phage therapy. Most improve gut permeability, liver inflammation, and fibrosis through microbiota regulation, and are promising alternatives for MASLFD management. However, most results come from animal studies, while clinical trials in MASLD patients are lacking. Further research is therefore needed in this area.}, }
@article {pmid40292220, year = {2025}, author = {Ma, P and Wang, R and Chen, H and Zheng, J and Yang, W and Meng, B and Liu, Y and Lu, Y and Zhao, J and Gao, H}, title = {Fecal microbiota transplantation alleviates lipopolysaccharide-induced osteoporosis by modulating gut microbiota and long non-coding RNA TUG1 expression.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1535666}, pmid = {40292220}, issn = {2235-2988}, mesh = {Animals ; *RNA, Long Noncoding/genetics/metabolism ; *Gastrointestinal Microbiome/genetics ; *Osteoporosis/therapy/chemically induced/microbiology ; *Fecal Microbiota Transplantation/methods ; *Lipopolysaccharides/adverse effects ; Mice, Inbred C57BL ; Mice ; Disease Models, Animal ; RNA, Ribosomal, 16S/genetics ; Femur/pathology/diagnostic imaging ; Core Binding Factor Alpha 1 Subunit/metabolism ; X-Ray Microtomography ; Male ; }, abstract = {PURPOSE: To study whether fecal microbiota transplantation (FMT) can alleviate lipopolysaccharide (LPS)-induced osteoporosis (OP) by regulating the composition and abundance of gut microbiota and the expression level of long non-coding RNA (lncRNA) TUG1.<br><br>METHODS: Twenty C57BL/6 mice were selected. Two mice were randomly designated as fecal donors, while the remaining mice were randomly divided into control group, LPS group, and LPS + FMT group. Each group consisted of 6 mice. The mice in the LPS and LPS + FMT groups were intraperitoneally injected with LPS to establish the OP model, and the mice in the LPS + FMT group were treated with donor feces by gavage. Micro-CT was used to scan the femur specimens of mice, and the bone structural parameters of the control and LPS groups were compared to verify the effectiveness of the OP model. HE staining was used to compare the microstructure of femurs in the 3 groups. 16S rRNA gene sequencing was used to analyze the composition and abundance of gut microbiota in mice. Immunofluorescence staining was used to compare the expression levels of Runt-related transcription factor 2 (RUNX2) in the femur of the 3 groups. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to compare the expression levels of lncRNA TUG1 in the intestines and serum of mice in the 3 groups.<br><br>RESULTS: Micro-CT showed that compared with the control group, the mice in the LPS group had more bone loss. The bone mineral density, trabecular number, and trabecular thickness of the control group was higher, and the trabecular separation was smaller. The models were validated effectively. HE staining showed that compared with the control group, the bone trabeculae in the LPS group were thinner and sparse, while that in the LPS + FMT group were dense and clear. The 16s rRNA sequencing showed that the abundance of Bacteroides and Lactobacillus in LPS+FMT group was significantly higher than that in LPS group. Immunofluorescence staining showed that the RUNX2 level in the control group and LPS + FMT group was similar, and both were higher than that in the LPS group. The qRT-PCR results showed that the TUG1 mRNA level in the control group and LPS + FMT group was similar and significantly higher than that in the LPS group.<br><br>CONCLUSION: FMT can enhance osteoblast levels and improve bone structure by modulating the abundance of gut microbiota in OP mice (such as increasing Bacteroides and Lactobacillus populations) and promoting the expression of lncRNA TUG1, thereby alleviating LPS-induced OP.}, }
@article {pmid40292216, year = {2025}, author = {Bu, F and Chen, K and Chen, S and Jiang, Y}, title = {Gut microbiota and intestinal immunity interaction in ulcerative colitis and its application in treatment.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1565082}, pmid = {40292216}, issn = {2235-2988}, mesh = {Humans ; *Colitis, Ulcerative/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/immunology ; *Immunity, Mucosal ; Intestinal Mucosa/immunology/microbiology ; Animals ; }, abstract = {Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease characterized by inflammation and injury of the colonic mucosa, exhibiting an increasing global incidence. Although research into UC pathogenesis is ongoing, the precise mechanisms remain to be fully elucidated. Studies indicate that UC development results from a complex interplay of factors, including genetic predisposition, environmental exposures, gut microbial dysbiosis, and immune dysregulation. Specifically, UC pathogenesis involves aberrant immune responses triggered by interactions between the host and gut microbiota. A complex, dynamic relationship exists between the microbial community and the host immune system throughout UC pathogenesis. Accumulating evidence suggests that changes in microbiota composition significantly impact gut immunity. This review will examine the intricate balance between the gut microbiota and mucosal immunity in UC progression and discuss potential therapeutic applications, providing a reference for further clinical treatment of this patient population.}, }
@article {pmid40291934, year = {2025}, author = {Mattar, L and Thalib, HI and Alnuwaimi, M and Alsaadi, H and Allouji, HA and Alyafei, J and Alshowiman, L and Alsobyani, N and Hassan, FES}, title = {Challenges of concurrent HIV infection in the course and management of Crohn's disease.}, journal = {Journal of medicine and life}, volume = {18}, number = {3}, pages = {171-178}, pmid = {40291934}, issn = {1844-3117}, mesh = {Humans ; *Crohn Disease/therapy/complications/immunology ; *HIV Infections/complications/immunology ; Disease Progression ; Probiotics/therapeutic use ; Gastrointestinal Microbiome ; }, abstract = {Crohn's disease (CD) is a chronic transmural bowel inflammation with a multifactorial etiology involving genetic predisposition and immune dysregulation in response to environmental triggers. In patients with human immunodeficiency virus (HIV), an already compromised immune system further complicates the progression and management of CD, creating unique therapeutic challenges. Probiotics have recently gained attention as a potential therapeutic option for CD, especially due to their role in modulating the gut microbiota. However, their effectiveness in patients with HIV, especially in enhancing and maintaining remissions, remains underexplored. This review aimed to examine how HIV infection influences the course of inflammatory bowel disease (IBD) and its impact on CD management strategies. A systematic literature search was conducted using Google Scholar, PubMed, Springer, and Web of Science to identify studies on patients with HIV and CD. HIV infection significantly alters the progression and management of CD due to its impact on the immune system. The immunosuppressed state of patients with HIV can complicate both the diagnosis and treatment of CD, often requiring adjustments in therapeutic approaches, necessitating a careful, tailored approach.}, }
@article {pmid40289872, year = {2025}, author = {Gao, L and Zhang, Y and Hu, Z and Chen, S and Wang, Q and Zeng, Y and Yin, H and Zhao, J and Zhan, Y and Gao, C and Xin, Y and Chen, B and van der Veen, S and Zhao, M and Fang, D and Lu, Q}, title = {Microbiota-Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2409837}, doi = {10.1002/advs.202409837}, pmid = {40289872}, issn = {2198-3844}, support = {2022YFC3601800//National Key R&amp;D Program of China/ ; 32141004//Special Program of National Natural Science Foundation of China/ ; 2021-I2M-1-059//CAMS Innovation Fund for Medical Sciences (CIFMS) No/ ; 2024-I2M-ZH-020//CAMS Innovation Fund for Medical Sciences (CIFMS) No/ ; 2020-RC320-003//Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; NO.82430102//Key Program of the National Natural Science Foundation of China/ ; 82404154//National Natural Science Foundation of China/ ; }, abstract = {The role of gut microbiota dysbiosis in systemic lupus erythematosus (SLE) pathogenesis remains elusive. Here, it is shown that fecal microbiota transplantation (FMT) from healthy mice to lupus mice ameliorates lupus-like symptoms. Microbiota reconstitution effectively reduces systemic class switch recombination (CSR) and elevates immunoglobulin heavy chain (IGH) naïve isotype. Microbiota profiling reveals an enrichment of Lactobacillus johnsonii post-FMT, with a significant correlation to purine metabolites. Importantly, the L. johnsonii-derived inosine, an intermediate metabolite in purine metabolism, effectively alleviates lupus pathogenesis in mice. Inosine inhibits B cell differentiation and reduces renal B cell infiltration to protect mice from lupus. At the molecular level, inosine reprograms B cells through the eDDxtracellular signal-regulated kinase (ERK)-hypoxia-inducible factor-1alpha (HIF-1α) signaling pathway. Therefore, this study highlights the discovery of a novel microbial metabolite modulating autoimmunity and suggests its potential for innovative microbiome-based therapeutic approaches.}, }
@article {pmid40289678, year = {2025}, author = {Xu, Z and Li, L and Cheng, L and Gu, Z and Hong, Y}, title = {Maternal obesity and offspring metabolism: revisiting dietary interventions.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4fo06233g}, pmid = {40289678}, issn = {2042-650X}, abstract = {Maternal obesity increases the risk of metabolic disorders in offspring. Understanding the mechanisms underlying the transgenerational transmission of metabolic diseases is important for the metabolic health of future generations. More research is needed to elucidate the mechanisms underlying the associated risks and their clinical implications because of the inherently complex nature of transgenerational metabolic disease transmission. Diet is a well-recognized risk factor for the development of obesity and other metabolic diseases, and rational dietary interventions are potential therapeutic strategies for their prevention. Despite extensive research on the physiological effects of diet on health and its associated mechanisms, little work has been devoted to understanding the effects of early-life dietary interventions on the metabolic health of offspring. In addition, existing dietary interventions are insufficient to meet clinical needs. Here, we discuss the literature on the effects of maternal obesity on the metabolic health of offspring, focusing on the mechanisms underlying the transgenerational transmission of metabolic diseases. We revisit current dietary interventions and describe their strengths and weaknesses in ameliorating maternal obesity-induced metabolism-related disorders in offspring. We also propose innovative strategies, such as the use of precision nutrition and fecal microbiota transplantation, which may limit the vicious cycle of intergenerational metabolic disease transmission.}, }
@article {pmid40289444, year = {2025}, author = {Grimstad, T and Carlsen, A and Kvaløy, JT and Bolstad, N and Warren, DJ and Aabakken, L and Lundin, KEA and Karlsen, L and Steinsbø, &#xd8; and Omdal, R}, title = {Fatigue in Inflammatory Bowel Disease: No Effect of Serum Concentrations of Infliximab, Adalimumab or Anti-Drug Antibodies During Maintenance Therapy.}, journal = {Scandinavian journal of immunology}, volume = {101}, number = {5}, pages = {e70029}, doi = {10.1111/sji.70029}, pmid = {40289444}, issn = {1365-3083}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Adalimumab/therapeutic use/blood/immunology ; Antibodies/blood ; C-Reactive Protein/metabolism ; *Colitis, Ulcerative/drug therapy ; *Crohn Disease/drug therapy ; Cross-Sectional Studies ; *Fatigue/drug therapy/etiology/blood ; Feces/chemistry ; *Inflammatory Bowel Diseases/drug therapy/complications ; *Infliximab/blood/therapeutic use/immunology ; Leukocyte L1 Antigen Complex/metabolism ; Severity of Illness Index ; }, abstract = {Several studies have shown that infliximab and adalimumab ameliorate fatigue in inflammatory bowel disease. We investigated whether serum levels of these agents above or below a selected threshold influence fatigue severity. In this cross-sectional study, we measured serum concentrations (s-) of infliximab and adalimumab and corresponding anti-drug antibody levels. Therapeutic thresholds were defined as s-infliximab ≥ 5.0 mg/L and s-adalimumab ≥ 7.0 mg/L. Disease activity was assessed using the Harvey-Bradshaw Index for Crohn's disease, Partial Mayo Score for ulcerative colitis, and C-reactive protein (CRP) and faecal calprotectin levels for both conditions. Fatigue was assessed with the Fatigue Visual Analog Scale and Fatigue Severity Scale, and depression was evaluated with the Hospital Anxiety and Depression Scale, Depression subscale. Of 171 included patients (112 with Crohn's disease, 59 with ulcerative colitis), 66 (38.6%) were on infliximab and 105 (61.4%) were on adalimumab. Scores on the two fatigue scales were similar for serum values above versus below therapeutic thresholds for both drugs and did not differ with versus without anti-drug antibodies against either drug. CRP was numerically higher with infliximab levels below versus above the threshold (p = 0.06), whereas both CRP and faecal calprotectin were increased with adalimumab below versus above the threshold (p = 0.022, p = 0.0242). In patients with inflammatory bowel disease on maintenance therapy, s-infliximab and s-adalimumab levels below or above therapeutic thresholds or the presence of anti-drug antibodies did not affect fatigue severity. Trial Registration: ClinicalTrials.gov identifier: NCT02134054.}, }
@article {pmid40288637, year = {2025}, author = {La Rosa, F and Guzzardi, MA and Pardo-Tendero, M and Barone, M and Ruocco, C and Conti, G and Panetta, D and Riabitch, D and Bernardi, S and Giorgetti, A and Campani, D and Monleon, D and Nisoli, E and Brigidi, P and Iozzo, P}, title = {Effects of Children's microbiota on adipose and intestinal development in sex-matched mice persist into adulthood following a single fecal microbiota transplantation.}, journal = {Molecular metabolism}, volume = {}, number = {}, pages = {102157}, doi = {10.1016/j.molmet.2025.102157}, pmid = {40288637}, issn = {2212-8778}, abstract = {BACKGROUND: The global prevalence of obesity and type 2 diabetes, particularly among children, is rising, yet the long-term impacts of early-life fecal microbiota transplantation (FMT) on metabolic health remain poorly understood.<br><br>OBJECTIVES: To investigate how early-life FMT from children to young, sex-matched mice influences metabolic outcomes and adipose tissue function in later, adult life.<br><br>METHODS: Germ-free mice were colonized with fecal microbiota from either lean children or children with obesity. The impacts on brown adipose tissue (BAT), white adipose tissue (WAT), glucose metabolism, and gut health were analyzed in male and female mice. Microbial communities and metabolite profiles were characterized using sequencing and metabolomics.<br><br>RESULTS: Male mice receiving FMT from obese donors exhibited marked BAT whitening and impaired amino acid and glucose metabolism. In contrast, female recipients developed hyperglycemia, accompanied by gut barrier dysfunction and WAT impairment. Distinct microbial and metabolite profiles were associated with these phenotypes: Collinsella and trimethylamine in females; and Paraprevotella, Collinsella, Lachnospiraceae NK4A136, Bacteroides, Coprobacillus, and multiple metabolites in males. These phenotypic effects persisted despite changes in host environment and diet.<br><br>CONCLUSIONS: Early-life FMT induced long-lasting effects on the metabolic landscape, profoundly affecting adipose tissue function and systemic glucose homeostasis in adulthood. Donor dietary habits correlated with the fecal microbial profiles observed in recipient mice. These findings highlight the critical need for identifying and leveraging beneficial exposures during early development to combat obesity and diabetes.}, }
@article {pmid40288317, year = {2025}, author = {Banerjee, A and Mal, S and Roy, P and Chatterji, U}, title = {Regulating environmental arsenic-mediated gut-brain toxicity using chitosan-conjugated luteolin gold nanoparticles.}, journal = {Ecotoxicology and environmental safety}, volume = {297}, number = {}, pages = {118250}, doi = {10.1016/j.ecoenv.2025.118250}, pmid = {40288317}, issn = {1090-2414}, abstract = {Anxiety and depression are two major contributors to global disease burden. Amongst various causal factors, exposure to even low doses of environmental heavy metals, like arsenic, can induce anxiety and depression-like behaviour in mammals. Ingestion of arsenic, primarily through contaminated drinking water, severely disrupts the gut microbes, thereby inducing structural and functional abnormalities in the brain. Fecal microbiota transplantation (FMT) from arsenic-exposed mice to recipient healthy mice (As-FMT) enriched LPS-secreting Gram-negative bacteria and upregulated the expression of TLR4 in intestinal epithelial cells. Consequently, inflammation, oxidative stress and compromised barrier integrity in the gut facilitated LPS translocation into the bloodstream and promoted systemic inflammation. The secretomes eventually affected the brain by activating microglia, altering neurotransmitter levels and reducing the glucocorticoid receptor (GR) expression, contributing to appearance of pyknotic nuclei in dentate gyrus of hippocampus and emergence of anxiety- and depression-like behaviour. Luteolin, a flavonoid, devoid of any apparent side-effects, yet known for its anti-inflammatory and antioxidant properties, showed potential in alleviating the gut-brain toxic effects. However, its limited solubility and bioavailability pose challenges for its effectiveness, for which chitosan-conjugated luteolin gold nanoparticles (CH-LuAuNPs) were synthesized. Interestingly, where FMT from arsenic-treated mice to healthy mice showed deleterious effects in the transplanted mice, FMT from arsenic-treated mice co-administered with CH-LuAuNP attenuated As-FMT-mediated disruption of the gut-brain axis. This study highlighted the critical contribution of healthy gut microbiota in preserving neurobehavioural physiology, as well as underscored the potential therapeutic benefits of luteolin nanoparticles in ameliorating arsenic-induced gut dysbiosis and consequent mental disorders.}, }
@article {pmid40287572, year = {2025}, author = {Zou, T and Tang, X and Wang, H and Shang, X and Liang, X and Ma, X}, title = {Nanocrystalline cellulose-geniposide complex enhances gut-brain axis modulation for depression treatment.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {667}, pmid = {40287572}, issn = {2399-3642}, mesh = {Animals ; *Cellulose/chemistry/pharmacology ; Mice ; *Depression/drug therapy ; *Iridoids/pharmacology/chemistry ; *Nanoparticles/chemistry ; Gastrointestinal Microbiome/drug effects ; *Antidepressive Agents/pharmacology ; Male ; Fecal Microbiota Transplantation ; *Brain/drug effects/metabolism ; Mice, Inbred C57BL ; *Brain-Gut Axis/drug effects ; Disease Models, Animal ; }, abstract = {Depression, a major global health issue, is closely associated with imbalances in gut microbiota and altered intestinal functions. This study investigates the antidepressant potential of a composite of Geniposide (GP) and Nanocrystalline Cellulose (NCC), focusing on its effects on the gut-brain axis. Utilizing network pharmacology, GP was identified as a key compound targeting the BCL2 gene in depression management. Experimental approaches, including a chronic unpredictable mild stress (CUMS) model in mice, cellular assays, and fecal microbiota transplantation (FMT), were used to evaluate the composite's effectiveness. Results indicate that GP activates the adenosine monophosphate-activated protein kinase (AMPK) pathway by upregulating BCL2, enhancing intestinal barrier integrity, and balancing gut flora. These mechanisms contribute to its positive effects on hippocampal function and depressive-like behaviors in mice, suggesting that the GP-NCC composite could be a promising avenue for developing depression therapies that target gut health.}, }
@article {pmid40286751, year = {2025}, author = {Ji, H and Dong, Z and Yang, Y and Cui, W and Han, J and Hu, Y and Chen, H and Qiao, C and Li, Q and Li, H and Wu, S}, title = {Neixiao-ruanmai decoction No 2 improves carotid atherosclerosis by modulating gut microbiota and inhibiting TLR4/NF-κB pathway activation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {142}, number = {}, pages = {156775}, doi = {10.1016/j.phymed.2025.156775}, pmid = {40286751}, issn = {1618-095X}, abstract = {BACKGROUND: Carotid atherosclerosis(CAs) plaques are challenging to reverse. Neixiao-Ruanmai Decoction No 2(NXRMT No 2), a Traditional Chinese Medicine (TCM) decoction, has shown potential in treating CAs. However, while preliminary clinical trials have confirmed the efficacy of NXRMT No 2 in improving CAs, the comparative effectiveness of long-term versus short-term treatment courses remains unclear, and the underlying mechanisms of this decoction are not yet fully understood.<br><br>METHODS: We conducted clinical trials, animal studies, 16S rRNA sequencing, metabolomics and fecal microbiota transplantation.<br><br>RESULT: Clinical research results indicate that NXRMT No 2(24 weeks of treatment) reduced total plaque area by 22.02%, maximum plaque thickness by 7.91%, and maximum plaque area by 21.29%. NXRMT No 2 improves patients'serum inflammatory levels, with a 24-week treatment course demonstrated superior efficacy compared to the 12-week treatment. Animal experiments demonstrated that NXRMT No 2 improved CAs progression, modulated the gut microbiota, inhibited the intestinal Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-&#x3ba;B) pathway and activated the expression of intestinal tight junction proteins.<br><br>CONCLUSION: NXRMT No 2 significantly attenuates CAs progression, with its primary mechanism likely related to modulating the gut microbiota to counteract the TLR4/NF-&#x3ba;B pathway and protect the intestinal barrier. This study provides evidence-based support for the use of NXRMT No 2 in treating CAs, offers guidance on optimal treatment duration for patients, and contributes to the development of traditional Chinese medicine formulations that improve CAs by modulating the gut microbiota-a significant advance in the prevention and treatment of CAs.}, }
@article {pmid40285477, year = {2025}, author = {Hansen, SH and Maseng, MG and Grännö, O and Vestergaard, MV and Bang, C and Olsen, BC and Lund, C and Olbjørn, C and Løvlund, EE and Vikskjold, FB and Huppertz-Hauss, G and Perminow, G and Yassin, H and Valeur, J and Aass Holten, KI and Henriksen, M and Bengtson, MB and Ricanek, P and Opheim, R and Boyar, R and Torp, R and Frigstad, SO and Aabrekk, TB and Detlie, TE and Kristensen, VA and Strande, V and Hovde, &#xd8; and Asak, &#xd8; and Jess, T and Franke, A and Halfvarsson, J and Høivik, ML and Hov, JR}, title = {Fecal Microbiome Reflects Disease State and Prognosis in Inflammatory Bowel Disease in an Adult Population-Based Inception Cohort.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf060}, pmid = {40285477}, issn = {1536-4844}, support = {//Pfizer/ ; //Tillotts Pharma/ ; //Dam Foundation/ ; //Norwegian South-Eastern Health Authorities/ ; 2020066//Regional Health Authorities South-Eastern Norway/ ; 327634//Research Council of Norway/ ; //Bio-Me AS/ ; //DFG Excellence Cluster 2167/ ; //DFG Research Unit/ ; DNRF148//National Research Foundation/ ; }, abstract = {INTRODUCTION: We aimed to determine the diagnostic and prognostic potential of baseline microbiome profiling in inflammatory bowel disease (IBD).<br><br>METHODS: Participants with ulcerative colitis (UC), Crohn's disease (CD), suspected IBD, and non-IBD symptomatic controls were included in the prospective population-based cohort Inflammatory Bowel Disease in South-Eastern Norway III (third iteration) based on suspicion of IBD. The participants donated fecal samples that were analyzed with 16S rRNA sequencing. Disease course severity was evaluated at the 1-year follow-up. A stringent statistical consensus approach for differential abundance analysis with 3 different tools was applied, together with machine learning modeling.<br><br>RESULTS: A total of 1404 individuals were included, where n&#x2005;=&#x2005;1229 samples from adults were used in the main analyses (n&#x2005;=&#x2005;658 UC, n&#x2005;=&#x2005;324 CD, n&#x2005;=&#x2005;36 IBD-U, n&#x2005;=&#x2005;67 suspected IBD, and n&#x2005;=&#x2005;144 non-IBD symptomatic controls). Microbiome profiles were compared with biochemical markers in machine learning models to differentiate IBD from non-IBD symptomatic controls (area under the receiver operating curve [AUC] 0.75-0.79). For UC vs controls, integrating microbiome data with biochemical markers like fecal calprotectin mildly improved classification (AUC 0.83 to 0.86, P&#x2005;<&#x2005;.0001). Extensive differences in microbiome composition between UC and CD were identified, which could be quantified as an index of differentially abundant genera. This index was validated across published datasets from 3 continents. The UC-CD index discriminated between ileal and colonic CD (linear regression, P&#x2005;=&#x2005;.008) and between colonic CD and UC (P&#x2005;=&#x2005;.005), suggesting a location-dependent gradient. Microbiome profiles outperformed biochemical markers in predicting a severe disease course in UC (AUC 0.72 vs 0.65, P&#x2005;<&#x2005;.0001), even in those with a mild disease at baseline (AUC 0.66 vs 0.59, P&#x2005;<&#x2005;.0001).<br><br>CONCLUSIONS: Fecal microbiome profiling at baseline held limited potential to diagnose IBD from non-IBD compared with standard-of-care. However, microbiome shows promise for predicting future disease courses in UC.}, }
@article {pmid40284630, year = {2025}, author = {Zhang, Y and Wang, L and Peng, L}, title = {The Role of Intestinal Fungi in the Pathogenesis and Treatment of Ulcerative Colitis.}, journal = {Microorganisms}, volume = {13}, number = {4}, pages = {}, pmid = {40284630}, issn = {2076-2607}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely associated with dysbiosis of the gut microbiome, encompassing not only bacterial communities but also fungal populations. Despite the growing recognition of the gut microbiome's role in UC pathogenesis, the contribution of intestinal fungi has only recently garnered significant attention. In this review, we comprehensively examine the characteristics of intestinal fungi in both healthy individuals and UC patients, elucidating their role in disease pathogenesis and their interactions with bacterial communities. Additionally, we explore the impact of intestinal fungi on disease severity and therapeutic responses in UC. Furthermore, we evaluate the therapeutic potential of antifungal agents, probiotics, and fecal microbiota transplantation (FMT) in UC management, emphasizing the critical role of fungi in these treatment modalities. Future research should prioritize elucidating the multifunctional roles of fungi in UC pathogenesis and their implications for treatment strategies. Moreover, the identification of fungal biomarkers associated with FMT efficacy could pave the way for precision medicine approaches in FMT, offering novel insights into personalized therapeutic interventions for UC.}, }
@article {pmid40284188, year = {2025}, author = {Bonomo, MG and D'Angelo, S and Picerno, V and Carriero, A and Salzano, G}, title = {Recent Advances in Gut Microbiota in Psoriatic Arthritis.}, journal = {Nutrients}, volume = {17}, number = {8}, pages = {}, pmid = {40284188}, issn = {2072-6643}, mesh = {Humans ; *Arthritis, Psoriatic/microbiology/therapy/immunology ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by joint inflammation and skin lesions. Recent research has underscored the critical role of gut microbiota-comprising bacteria, fungi, viruses, and archaea-in the pathogenesis and progression of PsA. This narrative review synthesizes the latest findings on the influence of gut microbiota on PsA, focusing on mechanisms such as immune modulation, microbial dysbiosis, the gut-joint axis, and its impact on treatment. Advances in high-throughput sequencing and metagenomics have revealed distinct microbial profiles associated with PsA. Studies show that individuals with PsA have a unique gut microbiota composition, differing significantly from healthy controls. Alterations in the abundance of specific bacterial taxa, including a decrease in beneficial bacteria and an increase in potentially pathogenic microbes, contribute to systemic inflammation by affecting the intestinal barrier and promoting immune responses. This review explores the impact of various factors on gut microbiota composition, including age, hygiene, comorbidities, and medication use. Additionally, it highlights the role of diet, probiotics, and fecal microbiota transplantation as promising strategies to modulate gut microbiota and alleviate PsA symptoms. The gut-skin-joint axis concept illustrates how gut microbiota influences not only gastrointestinal health but also skin and joint inflammation. Understanding the complex interplay between gut microbiota and PsA could lead to novel, microbiome-based therapeutic approaches. These insights offer hope for improved patient outcomes through targeted manipulation of the gut microbiota, enhancing both diagnosis and treatment strategies for PsA.}, }
@article {pmid40283508, year = {2025}, author = {Boicean, A and Ichim, C and Sasu, SM and Todor, SB}, title = {Key Insights into Gut Alterations in Metabolic Syndrome.}, journal = {Journal of clinical medicine}, volume = {14}, number = {8}, pages = {}, pmid = {40283508}, issn = {2077-0383}, abstract = {Over time, extensive research has underscored the pivotal role of gut microbiota in the onset and progression of various diseases, with a particular focus on fecal microbiota transplantation (FMT) as a potential therapeutic approach. The practice of transferring fecal matter from a healthy donor to a patient provides valuable insights into how alterations in gut microbiota can impact disease development and how rectifying dysbiosis may offer therapeutic benefits. Re-establishing a balanced symbiotic relationship in the gastrointestinal tract has shown positive results in managing both intestinal and systemic conditions. Currently, one of the most pressing global health issues is metabolic syndrome-a cluster of conditions that includes insulin resistance, lipid imbalances, central obesity and hypertension. In this context, FMT has emerged as a promising strategy for addressing key components of metabolic syndrome, such as improving insulin sensitivity, body weight and lipid profiles. However, further well-structured studies are needed to refine treatment protocols and establish the long-term safety and efficacy of this intervention.}, }
@article {pmid40283148, year = {2025}, author = {Marano, G and Rossi, S and Sfratta, G and Traversi, G and Lisci, FM and Anesini, MB and Pola, R and Gasbarrini, A and Gaetani, E and Mazza, M}, title = {Gut Microbiota: A New Challenge in Mood Disorder Research.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, pmid = {40283148}, issn = {2075-1729}, abstract = {The gut microbiome has emerged as a novel and intriguing focus in mood disorder research. Emerging evidence demonstrates the significant role of the gut microbiome in influencing mental health, suggesting a bidirectional communication between the gut and the brain. This review examines the latest findings on the gut-microbiota-brain axis and elucidates how alterations in gut microbiota composition can influence this axis, leading to changes in brain function and behavior. Although dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation have yielded encouraging results, significant advances are needed to establish next-generation approaches that precisely target the neurobiological mechanisms of mood disorders. Future research must focus on developing personalized treatments, facilitated by innovative therapies and technological progress, which account for individual variables such as age, sex, drug history, and lifestyle. Highlighting the potential therapeutic implications of targeting the gut microbiota, this review emphasizes the importance of integrating microbiota research into psychiatric studies to develop more effective and personalized treatment strategies for mood disorders.}, }
@article {pmid40282300, year = {2025}, author = {Nemati, MH and Yazdanpanah, E and Kazemi, R and Orooji, N and Dadfar, S and Oksenych, V and Haghmorad, D}, title = {Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential.}, journal = {Biology}, volume = {14}, number = {4}, pages = {}, pmid = {40282300}, issn = {2079-7737}, abstract = {Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut-brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., Prevotella and Faecalibacterium) were suggested to lay protective roles, whereas Akkermansia muciniphila was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut-brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.}, }
@article {pmid40281872, year = {2025}, author = {Dipasquale, V and Romano, C}, title = {New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {40281872}, issn = {2227-9032}, abstract = {Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care.}, }
@article {pmid40280962, year = {2025}, author = {Wissel, EF and Chien, HY and Wei, KH and Lee, YC and Ullah, K and Hsieh, PCH}, title = {Microbial metabolites associated in stool and left ventricle of heart failure patients revealed by meta-analysis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {14576}, pmid = {40280962}, issn = {2045-2322}, support = {110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; }, mesh = {Humans ; *Heart Failure/microbiology/metabolism ; *Feces/microbiology ; *Heart Ventricles/metabolism/microbiology ; Metabolomics/methods ; *Gastrointestinal Microbiome ; Metabolome ; }, abstract = {Heart Failure (HF) impacts approximately 64 million people globally. While overall incidence of HF is relatively stable across countries, the overall number of HF patients is increasing due to aging populations. Many articles examine the microbiome in HF, however, studies from humans have not been analyzed systematically. The aim of this meta-analysis is to bridge this gap by analyzing previously published data on human HF patients with untargeted metabolomics to understand whether microbially-mediated metabolites are consistently important for HF status. A systematic survey of the literature identified 708 articles discussing HF, the microbiome, and metabolomics. Of these, 82 were primary studies of HF patients, 61 studied human adults, 23 included an untargeted metabolomics measure, and 3 studies had data that was usable and publicly accessible. These studies include a GCMS study from stool, NMR of saliva and exhaled breath condensate, and LCMS from left ventricle of HF patients undergoing transplantation and unused donor hearts. Significant differences were observed from PCA between HF and controls for stool and left ventricle, but not saliva or EBC samples. OPLS-DA was conducted for stool and ventricle samples, and further revealed significant group differences. Univariate testing with FDR correction revealed 8 significant microbially-relevant metabolites (p < 0.005 after correction), most notably asparagine from left ventricle and 2-methylbutyryl carnitine from stool. Though there is much discussion of the microbiome in health outcomes in HF, there is limited research from human populations. Some microbial co-metabolites from both stool and heart were significantly associated with HF.}, }
@article {pmid40280130, year = {2025}, author = {Wellens, J and Vissers, E and Dumoulin, A and Hoekx, S and Vanderstappen, J and Verbeke, J and Vangoitsenhoven, R and Derrien, M and Verstockt, B and Ferrante, M and Matthys, C and Raes, J and Verbeke, K and Vermeire, S and Sabino, J}, title = {Cooking methods affect advanced glycation end products and lipid profiles: A randomized cross-over study in healthy subjects.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {102091}, doi = {10.1016/j.xcrm.2025.102091}, pmid = {40280130}, issn = {2666-3791}, abstract = {Thermal treatments used in ultra-processed foods (UPFs) lead to advanced glycation end products (AGEs). UPFs and serum AGEs are associated with cardiometabolic disease. We explore differential cooking methods as a mechanistic link between UPFs and detrimental health outcomes through a randomized cross-over cooking method trial in healthy subjects using identical ingredients and a deep profiling analysis. We show that low-AGE-generating cooking methods such as boiling and steaming decrease serum AGEs, improve lipid profiles, and increase serum protein 4E-BP1. In contrast, high-AGE-generating cooking methods such as grilling and baking increase fecal butyrate. In sum, this suggests that low-AGE-generating cooking methods should be considered in cardiovascular risk prevention. Since current dietary guidelines focus on ingredients, but not cooking methods, our results suggest that culinary techniques should be considered as an important factor in cardiometabolic preventive strategies and future dietary trial design. This study was registered at ClinicalTrials.gov (NCT06547190).}, }
@article {pmid40280127, year = {2025}, author = {Cai, W and Haddad, M and Haddad, R and Kesten, I and Hoffman, T and Laan, R and Westfall, S and Defaye, M and Abdullah, NS and Wong, C and Brown, N and Tansley, S and Lister, KC and Hooshmandi, M and Wang, F and Lorenzo, LE and Hovhannisyan, V and Ho-Tieng, D and Kumar, V and Sharif, B and Thurairajah, B and Fan, J and Sahar, T and Clayton, C and Wu, N and Zhang, J and Bar-Yoseph, H and Pitashny, M and Krock, E and Mogil, JS and Prager-Khoutorsky, M and Séguéla, P and Altier, C and King, IL and De Koninck, Y and Brereton, NJB and Gonzalez, E and Shir, Y and Minerbi, A and Khoutorsky, A}, title = {The gut microbiota promotes pain in fibromyalgia.}, journal = {Neuron}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuron.2025.03.032}, pmid = {40280127}, issn = {1097-4199}, abstract = {Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.}, }
@article {pmid40279964, year = {2025}, author = {Zheng, Z and Du, Y and Jiang, H and Shi, Z and Zhou, H and Jiao, L and Liu, P and Gong, Y}, title = {KAJF alleviated colorectal cancer liver metastasis by reshaping the gut microbiota and inhibiting M2-like macrophage polarization.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {142}, number = {}, pages = {156766}, doi = {10.1016/j.phymed.2025.156766}, pmid = {40279964}, issn = {1618-095X}, abstract = {BACKGROUND: Colorectal cancer liver metastasis (CRLM) represents one of the most severe complications of colorectal cancer (CRC), often associated with unfavorable prognosis. The herbal formulation Kang-Ai-Jing-Fang (KAJF) has been employed clinically against CRC for several decades, although its precise mechanism of action remains elusive.<br><br>PURPOSE: This study investigates the anti-metastatic potential of KAJF in CRLM, focusing on its modulatory effects on gut microbiota and inhibition of M2-like macrophage activation.<br><br>METHODS: KAJF was administered orally to CRLM model mice established through intrasplenic injection of murine CRC cells. To elucidate the role of gut microbiota reshaped by KAJF, fecal microbiota transplantation (FMT) was utilized to assess its impact on CRLM inhibition. Core targets and active compounds were identified through network pharmacology and molecular docking. To characterize microbiota composition, metabolite profiles, and gene expression variations, 16S rRNA sequencing, untargeted liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics, and transcriptomics analyses were performed.<br><br>RESULTS: KAJF demonstrated significant inhibitory effects on CRLM and ameliorated gut microbiota dysbiosis by enhancing the abundance of butyrate-producing bacteria (Lactobacillus, Bacteroides, Bifidobacterium). The therapeutic efficacy of KAJF-induced bacterial alterations in delaying CRLM and promoting butyrate-producing microbiota enrichment was further substantiated by FMT. Network pharmacology identified active ingredients in KAJF, including asperulosidic acid, polyphyllin II, ganoderenic acid B, calycosin, and ganoderic acid C, which exhibit substantial interactions with TLR4, PPAR&#x3b3;, SIRT1, PTGS2, and TNF. Molecular dynamics simulations and surface plasmon resonance (SPR) analysis demonstrated that ganoderic acid C2 exhibits a strong binding affinity for PPAR&#x3b3;. Moreover, KAJF administration led to a marked reduction in F4/80[+] CD206[+] macrophages and their associated cytokines (CCL17, CCL22, IL10, IL4, TGF), accompanied by a decrease in CD4[+] T cells and myeloid-derived suppressor cells (MDSCs), while increasing CD8[+] T cell populations.<br><br>CONCLUSIONS: This study demonstrates that KAJF mitigates CRLM, primarily through the regulation of gut microbiota and microbial metabolites, alongside inhibition of M2-like macrophage polarization. By integrating metabolomics, transcriptomics, and network pharmacology, this research elucidates the molecular mechanisms underpinning KAJF's therapeutic effects against CRLM, offering a promising approach for clinical intervention.}, }
@article {pmid40279942, year = {2025}, author = {Zhang, S and Qian, Y and Li, N and Zhu, Q and Zhang, S and Wen, P and Xiao, Y and Yan, C and Lin, Z and Zhong, J and Ma, J and Wu, X and Zhuang, G and Zhang, K}, title = {Specific MSI2 deletion maintains intestinal barrier integrity by down-regulating ILC3s-derived IL-17 a in mice with colitis.}, journal = {International immunopharmacology}, volume = {156}, number = {}, pages = {114717}, doi = {10.1016/j.intimp.2025.114717}, pmid = {40279942}, issn = {1878-1705}, mesh = {Animals ; *Interleukin-17/metabolism/immunology/genetics ; Dextran Sulfate ; *Intestinal Mucosa/immunology/pathology/metabolism ; Mice ; Disease Models, Animal ; *RNA-Binding Proteins/genetics ; Down-Regulation ; *Colitis, Ulcerative/immunology/chemically induced/genetics/pathology ; Mice, Inbred C57BL ; *Colon/pathology/immunology ; *Lymphocytes/immunology ; Mice, Knockout ; *Colitis/immunology/chemically induced ; Male ; Immunity, Innate ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease with an unknown cause. Previous studies have shown that Group 3 innate lymphoid cells (ILC3s) are crucial for maintaining intestinal mucosal immune homeostasis by producing key cytokines such as IL-22 and IL-17 A. While the RNA-binding protein Musashi-2 (MSI2) is recognized as essential for promoting intestinal epithelial regeneration post-injury, its impact on immune regulation remains unclear. Therefore, we aim to investigate the protective mechanisms associated with ILC3s-specific MSI2 deletion in a mouse model of ulcerative colitis.<br><br>METHODS: Dextran sulfate sodium (DSS) was used to induce a mouse colitis model. Colitis severity was evaluated through weight loss, diarrhea, fecal traits, colon length, and pathological scoring. Transcriptome sequencing was utilized to identify differentially expressed genes in colon tissues. Flow cytometry was employed to measure the quantity and functionality of ILC3s. Western blot was conducted to analyze protein expression, while real-time polymerase chain reaction and enzyme-linked immunosorbent assay were employed to quantify inflammatory factors. Additionally, immunofluorescence, AB-PAS staining, and immunohistochemistry were employed to evaluate the integrity of the intestinal barrier.<br><br>RESULTS: Following DSS treatment, colon damage was milder in Msi2[&#x2206;Rorc] mice than in Msi2[fl/fl] mice. Transcriptomic analysis revealed the down-regulation of cytokines and pro-inflammatory factors in the colon tissue of Msi2[&#x2206;Rorc] mice. Flow cytometry showed that specific deletion of MSI2 reduced the infiltration of ILC3s in the intestinal lamina propria of Msi2[&#x2206;Rorc] mice and decreased IL-17&#xa0;A production. The reduction of IL-17&#xa0;A-mediated immune responses lessened inflammatory damage to the intestinal barrier, thereby reducing colitis severity.<br><br>CONCLUSIONS: Specific deletion of MSI2 alleviates DSS-induced colitis in mice by reducing ILC3s infiltration and IL-17&#xa0;A secretion in the lamina propria of the colon. This decrease in inflammatory mediators and cell infiltration dampens the inflammatory response in the intestinal mucosa, helping to maintain the integrity of the intestinal barrier in mice with colitis. These findings enhance our understanding of UC pathogenesis and offer novel avenues for clinical diagnosis and treatment.}, }
@article {pmid40278398, year = {2025}, author = {Zheng, F and Yang, Y and Lu, G and Tan, JS and Mageswary, U and Zhan, Y and Ayad, ME and Lee, YY and Xie, D}, title = {Metabolomics Insights into Gut Microbiota and Functional Constipation.}, journal = {Metabolites}, volume = {15}, number = {4}, pages = {}, pmid = {40278398}, issn = {2218-1989}, support = {2024ZYD0149//Sichuan Science and Technology Program/ ; TB2024017//Special Research Foundation for the Postdoctoral Program of Sichuan Province/ ; 2024SZY004, 2024SZY016//Key Research and Development Project of Deyang Science and Technology Bureau/ ; 2022067//Chengdu Medical Research Project/ ; 2024JDKPO1117//Sichuan Science and Technology Program/ ; FHS202503//Projects of Deyang People's Hospital/ ; }, abstract = {Background: The composition and metabolic activity of the gut microbiota play a crucial role in various health conditions, including the occurrence and development of chronic constipation. Recent metabolomic advances reveal that gut microbiota-derived metabolites-such as SCFAs, bile acids, neurotransmitters, and microbial gases-play critical roles in regulating intestinal function. Methods: We systematically analyzed the current literature on microbial metabolomics in chronic constipation. This review consolidates findings from high-throughput metabolomic techniques (GC-MS, LC-MS, NMR) comparing metabolic profiles of constipated patients with healthy individuals. It also examines diagnostic improvements and personalized treatments, including fecal microbiota transplantation and neuromodulation, guided by these metabolomic insights. Results: This review shows that reduced SCFA levels impair intestinal motility and promote inflammation. An altered bile acid metabolism-with decreased secondary bile acids like deoxycholic acid-disrupts receptor-mediated signaling, further affecting motility. Additionally, imbalances in amino acid metabolism and neurotransmitter production contribute to neuromuscular dysfunction, while variations in microbial gas production (e.g., methane vs. hydrogen) further modulate gut transit. Conclusions: Integrating metabolomics with gut microbiota research clarifies how specific microbial metabolites regulate gut function. These insights offer promising directions for precision diagnostics and targeted therapies to restore microbial balance and improve intestinal motility.}, }
@article {pmid40274530, year = {2025}, author = {Ji, ZH and Xie, WY and Wu, HY and Yuan, B}, title = {Coix Seed Polysaccharide Mitigates Ulcerative Colitis in Mice through the Modulation of Gut Microbiota and Improvement of Intestinal Metabolism Balance.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {18}, pages = {11067-11079}, doi = {10.1021/acs.jafc.5c02458}, pmid = {40274530}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/microbiology/metabolism/drug therapy ; Mice ; *Polysaccharides/administration &amp; dosage ; Seeds/chemistry ; Male ; Mice, Inbred C57BL ; *Coix/chemistry ; Humans ; Bacteria/classification/genetics/isolation &amp; purification/drug effects ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; *Intestines/microbiology/drug effects/metabolism ; *Drugs, Chinese Herbal/administration &amp; dosage ; Colon/metabolism/drug effects/microbiology ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a rising incidence globally, whereas existing treatments exhibit significant limitations. Coix seed polysaccharide (CSP), a component of traditional Chinese medicine known for its immunomodulatory and antioxidant properties, has not been thoroughly investigated for its role in UC. In this study, CSP was prepared via water extraction and ethanol precipitation, and its protective effects and mechanisms were evaluated using a dextran sulfate sodium salt (DSS)-induced UC mouse model. The results demonstrated that CSP significantly ameliorated DSS-induced UC symptoms, including weight loss, an elevated Disease Activity Index, colon shortening, increased levels of inflammatory cytokines, and intestinal barrier damage. Moreover, CSP reshaped the DSS-induced gut microbiota dysbiosis by increasing gut microbial diversity and regulating the abundance of specific genera, such as increasing Anaerotruncus. Metabolomic analysis revealed that CSP significantly modulated the levels of 116 metabolites, particularly enhancing the beneficial metabolite 3-hydroxybutyrate. Importantly, the preventive effect of CSP on UC was dependent on the gut microbiota and could be transferred via fecal microbiota transplantation. This study demonstrates that CSP, a microecology-regulating polysaccharide, effectively modulates gut microbiota and alleviates symptoms of UC. These findings support the potential of CSP as a dietary supplement for UC prevention and underscore its value in the development of medicinal foods and functional food applications.}, }
@article {pmid40274437, year = {2025}, author = {Chang, Z and Zhu, Y and Wang, P and Du, L and Wu, M and Wang, X and Kong, C and Huang, D and Xie, R and Ji, G and Wang, C and Cheng, L and Yan, X and Wei, Q and Qin, H}, title = {Multi-omic analyses of the development of obesity-related depression linked to the gut microbe Anaerotruncus colihominis and its metabolite glutamate.}, journal = {Science bulletin}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.scib.2025.04.010}, pmid = {40274437}, issn = {2095-9281}, abstract = {Emerging evidence implicates gut microbiota in the pathogenesis of obesity-related depression (OD); however, the underlying molecular mechanisms remain inadequately explored. This study compared the microbial and transcriptional profiles between patients with OD and healthy individuals. The results revealed an enrichment of Anaerotruncus colihominis (A. colihominis) and glutamate metabolism-related genes in the OD group. Fecal microbiota transplantation (FMT) from patients with OD induced weight gain, compromised barrier function, and intensified depression-like behaviors in high-fat diet (HFD) mice. Microbial analysis in the mice feces corroborated the clinical findings. Single-cell RNA sequencing highlighted the pivotal role of the Efnb2-Ephb2 interaction in cell communication among colon epithelial and hippocampal neuron subtypes in OD mice. Notably, A. colihominis correlated with glutamate levels in the OD mice and patients. It produced glutamate through a glutamic acid metabolism-related DNA sequence, verified in an engineered Escherichia coli MG1655 strain. Both A. colihominis and glutamate reduced barrier proteins in colon epithelial cells and modulated cognitive proteins in neurons. Finally, A. colihominis treatment induced the Efnb2-Ephb2 interaction, exacerbating depression-like behaviors in germ-free HFD mice. Collectively, these findings reveal that A. colihominis and glutamate are potential intervention targets for OD treatment.}, }
@article {pmid40272913, year = {2025}, author = {Bohm, MS and Joseph, SC and Sipe, LM and Kim, M and Leathem, CT and Mims, TS and Willis, NB and Tanveer, UA and Elasy, JH and Grey, EW and Pye, ME and Mustafa, ZT and Harper, BA and McGrath, LG and Daria, D and Landvoigt Schmitt, B and Myers, JA and Pantoja Newman, P and Pence, BD and Van der Merwe, M and Davis, MJ and Pierre, JF and Makowski, L}, title = {The gut microbiome enhances breast cancer immunotherapy following bariatric surgery.}, journal = {JCI insight}, volume = {}, number = {}, pages = {}, doi = {10.1172/jci.insight.187683}, pmid = {40272913}, issn = {2379-3708}, abstract = {Bariatric surgery is associated with improved breast cancer (BC) outcomes, including greater immunotherapy effectiveness in a pre-clinical BC model. A potential mechanism of bariatric surgery-associated protection is the gut microbiota. Here, we demonstrate the dependency of improved immunotherapy response on the post-bariatric surgery gut microbiome via fecal microbial transplant (FMT). Response to αPD-1 immunotherapy was significantly improved following FMT from formerly obese bariatric surgery-treated mice. When stool from post-bariatric surgery patients was transplanted into recipient mice and compared to the patients' pre-surgery transplants, post-surgery microbes significantly reduced tumor burden and doubled immunotherapy effectiveness. Microbes impact tumor burden through microbially derived metabolites, including branched chain amino acids (BCAA). Circulating BCAAs correlated significantly with natural killer T (NKT) cell content in the tumor microenvironment in donor mice after bariatric surgery and FMT recipients of donor cecal content after bariatric surgery compared to obese controls. BCAA supplementation replicated improved αPD-1 effectiveness in two BC models, supporting the role of BCAAs in increased immunotherapy effectiveness after bariatric surgery. Ex vivo exposure increased primary NKT cell expression of anti-tumor cytokines, demonstrating direct activation of NKT cells by BCAAs. Together, findings suggest that reinvigorating anti-tumor immunity may depend upon bariatric surgery-associated microbially derived metabolites, namely BCAAs.}, }
@article {pmid40272874, year = {2025}, author = {Ubsdell, D and Maddox, NL and Sheridan, R}, title = {Management of severe and fulminant Clostridioides difficile infection in adults.}, journal = {Journal of medical microbiology}, volume = {74}, number = {4}, pages = {}, pmid = {40272874}, issn = {1473-5644}, mesh = {Humans ; *Clostridium Infections/therapy/microbiology/drug therapy ; *Clostridioides difficile/drug effects ; *Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Adult ; Metronidazole/therapeutic use ; }, abstract = {Clostridioides difficile (formerly known as Clostridium difficile) is a significant cause of healthcare-associated infection with symptoms ranging from diarrhoea and abdominal pain to pseudomembranous colitis and toxic megacolon. Severe disease can pose a significant morbidity and mortality risk and is to be considered a medical emergency. The emergence of a new C. difficile ribotype with an estimated mortality rate of 20% (ribotype 995) has prompted a re-review of the evidence and guidelines around managing severe C. difficile infections (CDI). International guidance on the management of CDI varies regarding first-line antibiotic choice. Metronidazole is no longer favoured as first line due to concerns around resistance, and vancomycin and fidaxomicin are now recommended as first line options. Antibiotic therapy should be used in conjunction with good supportive measures and early consideration of surgical management. Faecal microbiota transplant can be utilized in recurrent CDI and may be useful in severe disease. Severe CDI is a significant ongoing threat to public health, and further research into effective management is essential to ensure the best possible outcomes for patients.}, }
@article {pmid40272147, year = {2025}, author = {Dai, X and Cao, Y and Li, L and Gao, Y-X and Wang, J-X and Liu, Y-J and Ma, T-T and Zheng, J-M and Zhan, P-P and Shen, Z-Y}, title = {Gut microbiome and metabolome profiles in renal allograft rejection from multiomics integration.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0162624}, doi = {10.1128/msystems.01626-24}, pmid = {40272147}, issn = {2379-5077}, abstract = {UNLABELLED: The gut microbiome and metabolome play crucial roles in renal allograft rejection progression. Integrated multiomics analyses may provide a comprehensive understanding of specific underlying mechanisms, which remain elusive. This study aimed to identify new approaches for clinical renal allograft rejection diagnosis and treatment. Thirty-five patients were divided into three groups: the rejection (n = 16), dysfunction (n = 7), and control (n = 12) groups. Metagenomic sequencing and nontargeted metabolomics were used to analyze stool and plasma samples. Significant microbiota, metabolites, and signaling pathways were identified. LASSO regression was used to construct a diagnostic model, and its diagnostic value was assessed via receiver operating characteristic curves. The microbiota composition and the related genes in the rejection group significantly differed from that in the dysfunction and control groups at the phylum, genus, and species levels (P < 0.001). The core species in the rejection group networks were Escherichia coli and Ruminococcus gnavus, while core species in the dysfunction group networks were Faecalibacterium prausnitzii and Bacteroides ovatus. The balance of specific microbial species was associated with kidney function in rejection patients. Spearman analysis revealed that specific differential species like Agathobaculum butyriciproducens and Gemmiger qucibialis were closely linked to the levels of serum 4-pyridoxic acid, 4-acetamidobutanoate, and fecal tryptamine from specific differential pathways. Finally, we constructed four clinical models to distinguish the rejection and dysfunction groups, and the model had excellent diagnostic performance. Altered gut microbiota may contribute to changes in metabolic pathway activity and metabolite abundance in rejection and dysfunction patients, which are strongly correlated with host immunological rejection. The diagnostic model, developed based on the gut microbiota and metabolites, has high clinical value for diagnosing renal rejection.<br><br>IMPORTANCE: This study aimed to screen new markers for non-invasive diagnosis by the gut microbiome and metabolome analysis, providing new insights into rejection mechanisms and identifying new approaches for clinical renal allograft rejection diagnosis.}, }
@article {pmid40270478, year = {2025}, author = {Schoultz, I and Claesson, MJ and Dominguez-Bello, MG and Fåk Hållenius, F and Konturek, P and Korpela, K and Laursen, MF and Penders, J and Roager, H and Vatanen, T and Öhman, L and Jenmalm, MC}, title = {Gut microbiota development across the lifespan: Disease links and health-promoting interventions.}, journal = {Journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1111/joim.20089}, pmid = {40270478}, issn = {1365-2796}, abstract = {The gut microbiota plays a pivotal role in human life and undergoes dynamic changes throughout the human lifespan, from infancy to old age. During our life, the gut microbiota influences health and disease across life stages. This review summarizes the discussions and presentations from the symposium "Gut microbiota development from infancy to old age" held in collaboration with the Journal of Internal Medicine. In early infancy, microbial colonization is shaped by factors such as mode of delivery, antibiotic exposure, and milk-feeding practices, laying the foundation for subsequent increased microbial diversity and maturation. Throughout childhood and adolescence, microbial maturation continues, influencing immune development and metabolic health. In adulthood, the gut microbiota reaches a relatively stable state, influenced by genetics, diet, and lifestyle. Notably, disruptions in gut microbiota composition have been implicated in various inflammatory diseases-including inflammatory bowel disease, Type 1 diabetes, and allergies. Furthermore, emerging evidence suggests a connection between gut dysbiosis and neurodegenerative disorders such as Alzheimer's disease. Understanding the role of the gut microbiota in disease pathogenesis across life stages provides insights into potential therapeutic interventions. Probiotics, prebiotics, and dietary modifications, as well as fecal microbiota transplantation, are being explored as promising strategies to promote a healthy gut microbiota and mitigate disease risks. This review focuses on the gut microbiota's role in infancy, adulthood, and aging, addressing its development, stability, and alterations linked to health and disease across these critical life stages. It outlines future research directions aimed at optimizing the gut microbiota composition to improve health.}, }
@article {pmid40265594, year = {2025}, author = {Zhang, D and Zhang, Z and Liao, L and Dong, B and Xiong, X and Qin, X and Fan, X}, title = {Impact of fecal microbiota transplantation on lung function and gut microbiome in an ARDS rat model: A multi-omics analysis including 16S rRNA sequencing, metabolomics, and transcriptomics.}, journal = {International journal of immunopathology and pharmacology}, volume = {39}, number = {}, pages = {3946320251333982}, pmid = {40265594}, issn = {2058-7384}, mesh = {Animals ; *Gastrointestinal Microbiome ; Rats, Sprague-Dawley ; *Fecal Microbiota Transplantation/methods ; *Respiratory Distress Syndrome/therapy/microbiology/metabolism/physiopathology/genetics ; *Lung/metabolism/physiopathology/microbiology ; *RNA, Ribosomal, 16S/genetics ; Metabolomics/methods ; Disease Models, Animal ; Rats ; Male ; *Transcriptome ; Multiomics ; }, abstract = {OBJECTIVE: Acute respiratory distress syndrome (ARDS) is a severe pulmonary condition characterized by inflammation and lung damage, frequently resulting in poor clinical outcomes. Recent studies suggest that the gut-lung axis, mediated by gut microbiota, is critical in ARDS progression. This study investigates the therapeutic potential of fecal microbiota transplantation (FMT) in an ARDS rat model (n = 6).<br><br>INTRODUCTION: The pathogenesis of ARDS involves complex interactions between the lungs and gut, with microbiota playing a key role. Understanding the effects of FMT on lung function and gut microbiota may provide new therapeutic strategies for ARDS management.<br><br>METHODS: Sprague-Dawley rats were pre-treated with a broad-spectrum antibiotic cocktail to create a germ-free state and subsequently exposed to intranasal lipopolysaccharide to induce ARDS. The rats then received FMT treatment. Lung samples were analyzed using histopathology and transcriptomics. Fecal samples were analyzed using 16S rRNA sequencing and metabolomics.<br><br>RESULTS: FMT treatment significantly reduced lung injury and improved pulmonary function, as evidenced by increased partial pressure of arterial oxygen (PaO2) and decreased partial pressure of arterial carbon dioxide (PaCO2). FMT also significantly altered in gut microbiota composition by regulating the gut microbiota composition of Akkermansia and Lactobacillus, restoring the abundance of genera such as Muribaculaceae, Clostridia_UCG-014, Prevotella, and Adlercreutzia, while reducing Romboutsia. FMT restored key metabolic pathways involved in lipid metabolism, amino acid biosynthesis, and immune regulation, including the modulation of immune pathways like mTOR signaling. These alterations contribute to reduced lung injury and improved pulmonary function.<br><br>CONCLUSION: These findings indicate that FMT may exert its beneficial effects in ARDS by modulating the gut microbiota and enhancing metabolic and immune responses. However, given that this study remains in the preclinical stage, further validation in clinical studies is necessary before considering clinical application.}, }
@article {pmid40263850, year = {2025}, author = {He, G and Zhang, B and Chen, T and Shen, C and Wang, N and Yang, J and Chang, F and Sui, Y and Yin, X and Wang, Y and Wang, S and Li, Y and Zong, J and Luo, Y and Meng, Y and Li, C and Zhou, X}, title = {Effects of chitosan on restoring spermatogenesis in mice: Insights from gut microbiota and multi-omics analysis.}, journal = {Food research international (Ottawa, Ont.)}, volume = {208}, number = {}, pages = {116218}, doi = {10.1016/j.foodres.2025.116218}, pmid = {40263850}, issn = {1873-7145}, mesh = {Animals ; Male ; *Spermatogenesis/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Chitosan/pharmacology ; Mice ; Metabolomics ; Testis/drug effects/metabolism ; Busulfan ; Docosahexaenoic Acids/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Prebiotics ; Multiomics ; }, abstract = {Chitosan, is a natural bio-based polymer with known prebiotic properties. However, its potential in the management of spermatogenic disorders remains largely unexplored. By utilizing a busulfan-treated mouse model and integrated multi-omics analysis, this study explored the potential mechanisms through which chitosan improves impaired spermatogenesis. The results showed that chitosan treatment can improve testicular function and significantly reshape the gut microbiota composition in busulfan-treated mice. Metabolomics revealed that docosahexaenoic acid (DHA) transport was significantly dysregulated in busulfan-treated mice, but chitosan reversed this dysfunction by modulating tight junction proteins and fatty acid transporters in the intestine. Fecal microbiota transplantation experiments further highlighted the critical role of gut microbiota in DHA transport and spermatogenesis. Additionally, DHA supplementation alleviated busulfan-induced ferroptosis in testicular tissues. Hence, owing to its prebiotic effects chitosan could serve as a novel therapeutic strategy for improving busulfan-induced spermatogenic disorders by restoring the homeostasis of the gut-testis axis.}, }
@article {pmid40263438, year = {2025}, author = {Kumpunya, S and Kawang, K and Pollapong, K and Nilaratanakul, V}, title = {The effects of repeated fecal transplantation and activated charcoal treatment on gut dysbiosis induced by concurrent ceftriaxone administration in mice.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {13908}, pmid = {40263438}, issn = {2045-2322}, support = {RA-MF-52/64//Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University/ ; HEA_FF_68_079_3000_013//Thailand Science Research and Innovation Fund Chulalongkorn University/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Charcoal/pharmacology ; *Dysbiosis/chemically induced/therapy/microbiology ; *Ceftriaxone/adverse effects/administration &amp; dosage ; *Gastrointestinal Microbiome/drug effects ; Mice ; Mice, Inbred C57BL ; *Anti-Bacterial Agents/adverse effects/administration &amp; dosage ; RNA, Ribosomal, 16S/genetics ; Male ; Intestinal Mucosa/pathology/microbiology/drug effects ; }, abstract = {BACKGROUND: Antibiotic treatment contributes to gut microbiota dysbiosis. Previous studies have shown that fecal microbiota transplantation (FMT), fecal filtrate (FF), and activated charcoal (AC) treatments can prevent gut microbiota disturbances caused by antibiotics or Clostridioides difficile infection. However, these treatments have typically been limited to restoring gut microbiota after dysbiosis, and antibiotics must be discontinued beforehand. Here, we investigated the protective effects of these treatments on gut microbiota to prevent dysbiosis during concurrent systemic ceftriaxone administration.<br><br>METHODS: C57BL/6 mice that received intraperitoneal ceftriaxone for seven consecutive days were concomitantly treated with AC, FMT, FMT&#x2009;+&#x2009;AC, FF, or FF&#x2009;+&#x2009;AC via oral gavage. Gut microbiomes were analyzed using 16&#xa0;S rRNA gene sequencing, and intestinal mucosal pathology was evaluated through H&amp;E staining.<br><br>RESULTS: Systemic ceftriaxone administration significantly altered gut microbiota diversity and composition but did not affect intestinal mucosal histology. Alpha and beta diversity analyses showed that microbiota diversity decreased in all ceftriaxone-treated groups, with the ceftriaxone&#x2009;+&#x2009;FF&#x2009;+&#x2009;AC group retaining the highest diversity. The ceftriaxone&#x2009;+&#x2009;AC group had higher Enterococcus but lower Muribaculaceae relative abundances than the control (no ceftriaxone), ceftriaxone only, and ceftriaxone&#x2009;+&#x2009;FF&#x2009;+&#x2009;AC groups.<br><br>CONCLUSIONS: These results show that fecal filtrate transplantation combined with activated charcoal treatment may help balance gut microbiota diversity and reduce the presence of resistant bacteria during ceftriaxone exposure.}, }
@article {pmid40263148, year = {2025}, author = {Chi, Q and Tang, J and Ji, C and Chen, S and Chen, Q and Zeng, M and Cao, J and Sun, S and Herr, DR and Zhang, QG and Wang, Z and Huang, CM}, title = {Profiling electric signals of electrogenic probiotic bacteria using self-attention analysis.}, journal = {Applied microbiology and biotechnology}, volume = {109}, number = {1}, pages = {100}, pmid = {40263148}, issn = {1432-0614}, mesh = {*Probiotics/metabolism ; Animals ; Mice ; *Lactococcus lactis/metabolism/physiology ; Chorioallantoic Membrane/microbiology ; Glucose/metabolism ; *Electricity ; Chickens ; Intestines/microbiology ; }, abstract = {We fabricated a self-assembled electric circuit to detect the electrical signals produced by two electrogenic probiotic bacteria [Leuconostoc mesenteroides (L. mesenteroides) and Lactococcus lactis (L. lactis)] on chicken egg chorioallantoic membranes as well as in the intestine lumen of mice. Inoculation of L. mesenteroides or L. lactis plus glucose onto a ferrozine assay triggered the reduction of ferric ions to ferrous ions and the formation of ferrozine complexes, indicating the bacterial electron production. In the presence of glucose, L. lactis yielded higher electricity, measured by voltage changes, than L. mesenteroides in vitro. The spectra of the electrical signals generated by these two probiotic bacteria were highly distinguishable. We evaluated the importance of these differences with the application of a self-attention mechanism, a deep learning-based module, revealing several unique signals in the electrical spectra of L. mesenteroides as well as L. lactis bacteria. The specific electrical spectrum for each probiotic bacterium provided a dynamic signature for evaluation of the efficacy of various therapies using probiotics, antibiotics, and fecal microbiota transplantation in the future. KEY POINTS: • The electrical signals produced by probiotic bacteria L. mesenteroides and L. lactis on chicken egg chorioallantoic membranes and in the mouse intestine lumen were detectable. • In the presence of glucose, L. lactis yielded higher electricity than L. mesenteroides in vitro. Furthermore, the electrical spectra generated by these two bacteria were different. • The importance of these differences with the application of a self-attention mechanism revealed several unique signals in the electrical spectra.}, }
@article {pmid40262063, year = {2025}, author = {Elkrief, A and Routy, B and Derosa, L and Bolte, L and Wargo, JA and McQuade, JL and Zitvogel, L}, title = {Gut Microbiota in Immuno-Oncology: A Practical Guide for Medical Oncologists With a Focus on Antibiotics Stewardship.}, journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting}, volume = {45}, number = {3}, pages = {e472902}, doi = {10.1200/EDBK-25-472902}, pmid = {40262063}, issn = {1548-8756}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Antimicrobial Stewardship ; *Neoplasms/microbiology/immunology ; *Anti-Bacterial Agents/therapeutic use ; Immune Checkpoint Inhibitors/therapeutic use ; *Medical Oncology ; Oncologists ; }, abstract = {The gut microbiota has emerged as a critical determinant of immune checkpoint inhibitor (ICI) efficacy, resistance, and toxicity. Retrospective and prospective studies profiling the taxonomic composition of intestinal microbes of patients treated with ICI have revealed specific gut microbial signatures associated with response. By contrast, dysbiosis, which can be caused by chronic inflammatory processes (such as cancer) or comedications, is a risk factor of resistance to ICI. Recent large-scale meta-analyses have confirmed that antibiotic (ATB) use before or during ICI therapy alters the microbiota repertoire and significantly shortens overall survival, even after adjusting for prognostic factors. These results underscore the importance of implementing ATB stewardship recommendations in routine oncology practice. Microbiota-centered interventions are now being explored to treat gut dysbiosis and optimize ICI responses. Early-phase clinical trials evaluating fecal microbiota transplantation (FMT) from ICI responders or healthy donors have shown that this approach is safe and provided preliminary data on potential efficacy to overcome both primary and secondary resistance to ICI in melanoma, non-small cell lung cancer, and renal cell carcinoma. More targeted interventions including live bacterial products including Clostridium butyricum and Akkermansia massiliensis represent novel microbiome-based adjunct therapies. Likewise, dietary interventions, such as high-fiber diets, have shown promise in enhancing ICI activity. In this ASCO Educational Book, we summarize the current state-of-the-evidence of the clinical relevance of the intestinal microbiota in cancer immunotherapy and provide a practical guide for ATB stewardship.}, }
@article {pmid40261509, year = {2025}, author = {Mahgoup, EM}, title = {"Gut Microbiota as a Therapeutic Target for Hypertension: Challenges and Insights for Future Clinical Applications" "Gut Microbiota and Hypertension Therapy".}, journal = {Current hypertension reports}, volume = {27}, number = {1}, pages = {14}, pmid = {40261509}, issn = {1534-3111}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Hypertension/therapy/microbiology/physiopathology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Antihypertensive Agents/therapeutic use ; Blood Pressure/physiology ; Dysbiosis ; Prebiotics ; }, abstract = {PURPOSE OF REVIEW: Systemic hypertension is a major risk factor for cardiovascular disease and remains challenging to manage despite the widespread use of antihypertensive medications and lifestyle modifications. This review explores the role of gut microbiota in hypertension development and regulation, highlighting key mechanisms such as inflammation, gut-brain axis modulation, and bioactive metabolite production. We also assess the potential of microbiota-targeted therapies for hypertension management.<br><br>RECENT FINDINGS: Emerging evidence indicates that microbial dysbiosis, high-salt diets, and gut-derived metabolites such as short-chain fatty acids (SCFAs) and bile acids significantly influence blood pressure regulation. Preclinical and early clinical studies suggest that interventions targeting gut microbiota, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), and dietary modifications, may help modulate hypertension. However, variability in gut microbiota composition among individuals and limited human trial data pose challenges to translating these findings into clinical practice. While microbiota-based therapies show promise for hypertension management, further research is needed to establish their efficacy and long-term effects. Large-scale, standardized clinical trials are crucial for understanding the therapeutic potential and limitations of gut microbiota interventions. A deeper understanding of the gut-hypertension axis could lead to novel, personalized treatment strategies for hypertension.}, }
@article {pmid40260582, year = {2025}, author = {Shaukat, A and Drekonja, DM and Huang, Y and Zhang, JH and Davis-Karim, A and Kyriakides, TC}, title = {Efficacy and Safety of Fecal Microbiota Transplant for Prevention of Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf142}, pmid = {40260582}, issn = {1537-6591}, }
@article {pmid40260552, year = {2025}, author = {Davido, B and Kharkhordine, M and Moine, P}, title = {Fecal Microbiota Transplantation in Clostridioides Difficile Infections: Rethinking the Approach by Patient Profile in Light of New Evidence.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf143}, pmid = {40260552}, issn = {1537-6591}, }
@article {pmid40260548, year = {2025}, author = {Khoruts, A and Staley, C}, title = {FMT for Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf138}, pmid = {40260548}, issn = {1537-6591}, }
@article {pmid40260536, year = {2025}, author = {Paaske, SE and Baunwall, SMD and Ianiro, G and Iqbal, T and Keller, J and Kupciskas, J and Link, A and Mullish, BH and Vehreshild, MJGT and Dahlerup, JF and Hvas, CL}, title = {Clostridioides difficile: Treating Sustained Antibiotic Responders With Fecal Microbiota Transplantation Does Not Improve Efficacy.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf141}, pmid = {40260536}, issn = {1537-6591}, support = {//the National Institute of Health Research (NIHR) Imperial Biomedical Research Centre (BRC)/ ; //Imperial College London/ ; //Imperial College Healthcare NHS Trust/ ; MR/Z504002/1/MRC_/Medical Research Council/United Kingdom ; }, }
@article {pmid40259408, year = {2025}, author = {Cuisiniere, T and Hajjar, R and Oliero, M and Calvé, A and Fragoso, G and Rendos, HV and Gerkins, C and Taleb, N and Gagnon-Konamna, M and Dagbert, F and Loungnarath, R and Sebajang, H and Schwenter, F and Wassef, R and Ratelle, R and De Broux, &#xc9; and Richard, C and Santos, MM}, title = {Initial gut microbiota composition is a determining factor in the promotion of colorectal cancer by oral iron supplementation: evidence from a murine model.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {100}, pmid = {40259408}, issn = {2049-2618}, support = {PJT-159775/CAPMC/CIHR/Canada ; RGPIN-2024-05660//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Animals ; *Colorectal Neoplasms/microbiology/pathology/etiology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Iron/adverse effects/administration &amp; dosage ; Humans ; Disease Models, Animal ; *Dietary Supplements/adverse effects ; Fecal Microbiota Transplantation ; Male ; Female ; Administration, Oral ; Feces/microbiology ; Bacteria/classification/isolation &amp; purification/genetics ; Carcinogenesis/drug effects ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) development is influenced by both iron and gut microbiota composition. While iron supplementation is routinely used to manage anemia in CRC patients, it may also impact gut microbiota and promote tumorigenesis. In this study, we investigated the impact of initial gut microbiota composition on iron-promoted tumorigenesis. We performed fecal microbiota transplantation (FMT) in Apc[Min/+] mice using samples from healthy controls, CRC patients, and mice, followed by exposure to iron sufficient or iron excess diets.<br><br>RESULTS: We found that iron supplementation promoted CRC and resulted in distinct gut microbiota changes in Apc[Min/+] mice receiving FMT from CRC patients (FMT-CRC), but not from healthy controls or mice. Oral treatment with identified bacterial strains, namely Faecalibaculum rodentium, Holdemanella biformis, Bifidobacterium pseudolongum, and Alistipes inops, protected FMT-CRC mice against iron-promoted tumorigenesis.<br><br>CONCLUSIONS: Our findings suggest that microbiota-targeted interventions may mitigate tumorigenic effects of iron supplementation in anemic patients with CRC.}, }
@article {pmid40259351, year = {2025}, author = {Kamlárová, A and Kvaková, M and Ambro, &#x13d; and Link, R and Bertková, I and Hertelyová, Z and Janíčko, M and Hijová, E and Štofilová, J}, title = {Improvement of the inflammation-damaged intestinal barrier and modulation of the gut microbiota in ulcerative colitis after FMT in the SHIME® model.}, journal = {BMC complementary medicine and therapies}, volume = {25}, number = {1}, pages = {145}, pmid = {40259351}, issn = {2662-7671}, support = {APVV-23-0031//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja/ ; APVV-23-0031//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja/ ; APVV-23-0031//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja/ ; APVV-23-0031//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja/ ; APVV-23-0031//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; APVV-16-0176//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja,Slovakia/ ; APVV-16-0176//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja,Slovakia/ ; APVV-16-0176//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja,Slovakia/ ; APVV-16-0176//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja,Slovakia/ ; APVV-16-0176//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja,Slovakia/ ; APVV-16-0176//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja,Slovakia/ ; APVV-16-0176//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja,Slovakia/ ; APVV-16-0176//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja,Slovakia/ ; APVV-16-0176//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja,Slovakia/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; }, mesh = {*Colitis, Ulcerative/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Caco-2 Cells ; Inflammation ; HT29 Cells ; Male ; Female ; Intestinal Mucosa/microbiology ; Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) seems to be a promising approach in ulcerative colitis (UC) management with the aim of repopulating a patient's dysbiotic microbiota with beneficial bacteria and restore its metabolic activity to its healthy characteristics. Metabolites present after FMT may improve the function and integrity of the intestinal barrier, reduce inflammation, and thus induce remission in an UC patient. In this study we evaluated whether the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) model may be a suitable non-invasive alternative for studying and modifying the dysbiotic microbiota in UC by FMT application.<br><br>METHODS: SHIME&#xae; model was used to investigate microbial and metabolic changes in the gut microbiota of UC patient induced by FMT application. FMT-modified metabolites from SHIME&#xae; were applied to an in vitro model of the intestinal barrier (differentiated Caco-2 and HT-29-MTX-E12 cell lines) compromised by pro-inflammatory cytokines to study the effect of FMT on the intestinal barrier.<br><br>RESULTS: Qualitative and quantitative microbial analyses showed that FMT increased the diversity and variability of the microbiota in UC patient associated with a significant increase in total bacteria, Bacteroidota and Lactobacillus, as well as an increase in butyrate levels. In addition, an increase in the relative abundance of some important species such as Faecalibacterium prausnitzii and Bifidobacterium longum was observed, and there was also an enrichment of the microbiota with new species such as Blautia obeum, Roseburia faecis, Bifidobacterium adolescentis, Fusicatenibacter saccharivorans and Eubacterium rectale. Furthermore, microbial metabolites modulated by FMT from the SHIME&#xae; model prevented intestinal barrier damage and inhibited interleukin&#xa0;8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) secretion when cell barriers were pretreated with FMT medium for 24&#xa0;h. In summary, this study confirmed that a single dose of FMT beneficially modulated the composition and metabolic activity of the UC microbiota in the SHIME&#xae; model.<br><br>CONCLUSIONS: FMT favorably modulates the gut microbiota of UC patient cultured in the SHIME&#xae; model. FMT-modulated SHIME-derived microbial metabolites improve intact and inflamed intestinal barrier properties in vitro. Repeated applications are necessary to maintain the beneficial effect of FMT in SHIME&#xae; model.}, }
@article {pmid40258046, year = {2025}, author = {Lund, AJ and Metzger, ME and Kramer, VL and Kjemtrup, AM}, title = {Low risk for locally acquired Chagas disease in California: A review of human cases and triatomine submissions, 2013-2023.}, journal = {PLoS neglected tropical diseases}, volume = {19}, number = {4}, pages = {e0013036}, pmid = {40258046}, issn = {1935-2735}, support = {U50 CK000387/CK/NCEZID CDC HHS/United States ; }, mesh = {Animals ; Humans ; California/epidemiology ; *Chagas Disease/epidemiology/transmission/parasitology ; *Insect Vectors/parasitology ; *Triatominae/parasitology ; *Trypanosoma cruzi/isolation &amp; purification/genetics ; }, abstract = {Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi, which is carried in the guts of triatomine insects. Transmission typically occurs when infective trypomastigotes in triatomine feces encounter mucous membranes or bite wounds, though it is also possible by food-borne, transplant- and transfusion-mediated, and congenital routes. Most transmission occurs in rural and peri-urban parts of continental Latin America where triatomines often inhabit human dwellings. Triatomines infected with T. cruzi are also present across the southern United States, yet relatively few locally acquired infections have been documented. Rather, most reported cases have plausible exposure in Latin America. In California, the widespread distribution of T. cruzi-infected triatomines suggests a potential risk of local transmission. Here, we summarize triatomine submissions and human case reports made to the California Department of Public Health between 2013 and 2023. Of 226 triatomines tested, 63 (28%) were positive for T. cruzi via PCR; none were linked to any of the 40 human T. cruzi cases reported in the same period. Human cases were assessed for likelihood of local transmission. Country of birth, travel history, and location of primary residence suggested non-local transmission for 31 (78%) cases. Local transmission could not be ruled out for the remaining nine (22%) cases. Information on country of birth and travel history were missing from these case reports and prevented full assessment of local transmission criteria, though most of these patients resided within 400 meters of potential triatomine habitat. Despite the presence of triatomines, T. cruzi, and human cases in California, statewide data indicates the risk for locally acquired Chagas disease is low.}, }
@article {pmid40257861, year = {2025}, author = {Hu, M and Zhu, X and Huang, X and Hua, L and Lin, X and Zhang, H and Hu, Y and Tong, T and Li, L and Xuan, B and Zhao, Y and Zhou, Y and Ding, J and Ma, Y and Jiang, Y and Ning, L and Zhang, Y and Wang, Z and Fang, JY and Zhang, Y and Xiao, X and Hong, J and Chen, H and Li, J and Chen, H}, title = {Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype.}, journal = {Cell reports}, volume = {44}, number = {5}, pages = {115589}, doi = {10.1016/j.celrep.2025.115589}, pmid = {40257861}, issn = {2211-1247}, abstract = {Immunotherapy has revolutionized cancer treatment, but response variability remains a challenge. The gut microbiome's role in therapeutic efficacy is well established, but the impact of the gut mycobiome is less understood. Using unsupervised clustering, we identify two gut mycobiome-based enterotypes, favorable type and unfavorable type, characterized by distinct microbial compositions linked to immunotherapy outcomes. Favorable-type enterotypes exhibit higher fungal and bacterial alpha diversity, enriched butyrate-producing bacteria, and metabolic pathways related to butyric acid and sugar/starch metabolism. External validation confirms their predictive value in assessing immunotherapy efficacy. Multi-omics analysis reveals increased CD8[+] T cell infiltration in the tumor microenvironment of favorable-type patients. Fecal microbiota transplantation (FMT) from favorable-type donors enhances anti-PD-1 sensitivity, promotes CD8[+] T cell infiltration, and boosts butyrate production in vivo. These findings highlight the gut mycobiome's role in immunotherapy response and support FMT from favorable-type donors as a potential strategy for improving treatment outcomes and patient stratification.}, }
@article {pmid40257672, year = {2025}, author = {Bénard, MV and de Bruijn, CMA and Matamoros, S and Wentink-Bonnema, EMS and Benninga, MA and Ponsioen, CY and Zonneveld, R}, title = {Transient colonization with Blastocystis spp. after transmission via fecal microbiota transplantation.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, pmid = {40257672}, issn = {1435-4373}, abstract = {BACKGROUND: The pathogenicity of Blastocystis spp. is still debated. Guidelines for feces donor screening differ in their advice to screen for Blastocystis spp., but when tested, its presence is a common reason for exclusion. Blastocystis spp. are correlated to increased bacterial alpha-diversity and distinct bacterial groups and therefore its presence may indicate favorable efficacy of fecal microbiota transplantation (FMT). The latest European consensus report no longer advices rejecting feces donors testing positive for Blastocystis spp. Only one paper has been published on human transmission of Blastocystis spp. via frozen FMT.<br><br>OBJECTIVE: To investigate the transmission and long-term effects of Blastocystis-positive FMT, prepared with fresh (i.e., unfrozen) feces.<br><br>METHODS: In a trial (NCT03074227) on FMT for refractory Irritable Bowel Syndrome (IBS), adolescents (age 16-20 years) received two administrations - at baseline and after 6 weeks - of fresh allogeneic FMT from a Blastocystis-positive donor via nasoduodenal tube. The follow-up was 48 weeks. Blastocystis spp. presence, viability and subtyping were determined using microscopy, culture, PCR and sequencing.<br><br>RESULTS: Three recipients received FMT from one donor colonized with Blastocystis subtype 3 (ST3). At baseline, two recipients were negative for Blastocystis spp. and one recipient carried ST2. Culturing revealed viable Blastocystis spp. in fresh donor feces but not in frozen samples. After FMT with fresh feces, the two prior-negative recipients tested positive for the donor's ST3 at 12 weeks, but had lost this subtype by week 24 and 48. The recipient initially colonized with ST2 remained colonized with ST2 and did not acquire ST3. Transient adverse events occurred, but did not differ from patients treated with Blastocystis-negative FMT. No FMT-related serious adverse events emerged.<br><br>CONCLUSION: We present the first long-term data on viable Blastocystis spp. transmission via fresh FMT in three cases. Transient colonization with Blastocystis spp. was observed, without serious FMT-related adverse events.}, }
@article {pmid40257135, year = {2025}, author = {Deepti, I and Chettri, B and Mehra, A and Pinheiro, AM and Ravi, R}, title = {Faecal microbiota transplantation for recurrent Clostridiodes difficile infection &amp; its global regulatory landscape.}, journal = {The Indian journal of medical research}, volume = {161}, number = {2}, pages = {113-119}, pmid = {40257135}, issn = {0971-5916}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/therapy/microbiology ; *Clostridioides difficile/pathogenicity ; Recurrence ; Feces/microbiology ; Gastrointestinal Microbiome ; }, abstract = {For recurrent Clostridioides difficile infection (rCDI), faecal microbiota transplantation (FMT) is a known and useful treatment that involves introducing faeces from a healthy individual into the digestive tract of a diseased person. Clostridioides difficile is a substantial global health burden due to its high death rate in elderly populations and its ability to produce colitis and diarrhoea. Despite being used since millennia, FMT has recently become more well-known and two FMT products, namely Vowst and Rebyota also received FDA approval. Different nations address regulation in different ways. For instance, FMT is regulated as a drug in the US but is classified as a medicinal product in the UK. The regulatory frameworks among various European countries also vary; a working group, citing FMT as a transplant product, has requested for complete regulation. There are other classifications as well; in Australia, FMT is categorised as a biologic by the Therapeutic Goods Administration. Research indicates that FMT is beneficial in various illnesses, apart from CDI, due to its impact on the gut flora. Challenges include insufficient FMT product characterisation, ethical concerns, and limited hospital accessibility. There are still issues with data accessibility, security, and privacy, especially considering FMT's commercialisation. The official FMT recommendation for recurrent CDI is emphasised from the perspective of public health, with the argument that early implementation could limit antibiotic overuse and prevent antibiotic resistance. Initiatives like the Universal Stool Bank concept aim to streamline donor selection and distribution procedures to minimise operational restrictions.}, }
@article {pmid40256591, year = {2024}, author = {Abedi, B and Karimian, R and Bahari, Z and Iman, M}, title = {Absorbents therapy, as a conservative option, can improve kidney function in chronic kidney disease.}, journal = {Archives of Razi Institute}, volume = {79}, number = {4}, pages = {695-700}, pmid = {40256591}, issn = {2008-9872}, mesh = {Humans ; *Renal Insufficiency, Chronic/therapy/physiopathology ; *Renal Dialysis/methods ; *Conservative Treatment/methods ; }, abstract = {Chronic kidney disease (CKD), also called chronic kidney failure, is increasingly recognized as a global public health problem in the entire world. It is characterized by slow, progressive, and irreversible loss in kidney physiology. Today, the prevalence of CKD is increasing dramatically. CKD can affect almost every organ system, including the cardiovascular system. Many treatments have been attempted for CKD, such as renal transplantation, hemodialysis (HD), and peritoneal dialysis (PD). At the end stage of CKD, HD is the most widely used therapy throughout the world. However, these options can decrease volume expansion and uremic solute retention and also increase patient survival. Furthermore, there are certain complications associated with the use of these methods. Previous studies have reported that the main side effects are headaches, muscle cramps, abdominal pain, hypotension, hypertension, vomiting, and constipation. Therefore, the investigation for better and more convenient dialysis techniques should continue, as well as the search for a better material to enhance the clearance of nitrogenous waste products from the body. The intestine has a significant effect on the clearance of nitrogenous waste products from the body, making it a potentially appropriate site for CKD management. The potential mechanism of the intestinal dialysis technique is that it can absorb excess fluids, uremic toxins, and electrolytes within the gastrointestinal (GI) tract and exert them in the feces before they can be absorbed into the blood. In the present review, we will focus on different absorbents as a conservative treatment to remove uremic waste metabolites from the GI tract for the improvement of kidney function in CKD.}, }
@article {pmid40255763, year = {2025}, author = {Rathore, K and Shukla, N and Naik, S and Sambhav, K and Dange, K and Bhuyan, D and Imranul Haq, QM}, title = {The Bidirectional Relationship Between the Gut Microbiome and Mental Health: A Comprehensive Review.}, journal = {Cureus}, volume = {17}, number = {3}, pages = {e80810}, pmid = {40255763}, issn = {2168-8184}, abstract = {The gut microbiome plays a fundamental role in mental health, influencing mood, cognition, and emotional regulation through the gut-brain axis. This bidirectional communication system connects the gastrointestinal and CNS, facilitated by microbial metabolites, neurotransmitters, and immune interactions. Recent research highlights the association between gut dysbiosis and psychiatric disorders, including anxiety, depression, and stress-related conditions. Key findings indicate that altered microbial diversity, decreased short-chain fatty acid (SCFA) production, and increased neuroinflammation contribute to mental health disturbances. This paper explores the mechanism linking the gut microbiome to brain function, including microbial neurotransmitter synthesis, vagus nerve signaling, and hypothalamic-pituitary-adrenal (HPA) axis modulation. Additionally, it evaluates the potential of microbiome-targeted interventions, such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation (FMT), in alleviating psychiatric symptoms. Microbiome sequencing and bioinformatics advances further support the development of personalized microbiome-based mental health interventions. Despite promising evidence, challenges such as inter-individual variability, methodological inconsistencies, and the need for longitudinal studies remain. Future research should focus on standardizing microbiome assessment techniques and optimizing therapeutic applications. Integrating precision psychiatry with microbiome-based diagnostics holds immense potential in transforming mental health treatment.}, }
@article {pmid40254304, year = {2025}, author = {Fehily, SR and Wright, EK and Basnayake, C and Wilson-O'Brien, AL and Stanley, A and Marks, EP and Russell, EE and Hamilton, AL and Bryant, RV and Costello, SP and Kamm, MA}, title = {Faecal microbiota transplantation in Crohn's disease: an Australian randomised placebo-controlled trial protocol.}, journal = {BMJ open}, volume = {15}, number = {4}, pages = {e094714}, pmid = {40254304}, issn = {2044-6055}, mesh = {Humans ; *Crohn Disease/therapy ; *Fecal Microbiota Transplantation/methods ; Australia ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Remission Induction ; Adult ; Male ; Gastrointestinal Microbiome ; Female ; Multicenter Studies as Topic ; }, abstract = {INTRODUCTION: The enteric microbiota drives inflammation in Crohn's disease. Yet, there are no placebo controlled trials evaluating the efficacy and safety of faecal microbiota transplantation (FMT) in inducing and maintaining remission in patients with active Crohn's disease. The Microbial Restoration (MIRO) study aims to establish this evidence.<br><br>METHODS AND ANALYSIS: At two specialist inflammatory bowel disease centres, 120 enrolled patients will have a 3-week period of diet optimisation (removal of ultra-processed foods) together with a 7-day course of antibiotics (to facilitate subsequent FMT engraftment). Patients will then be stratified to upper gut (for disease proximal to the splenic flexure) or lower gut (distal to the splenic flexure) disease. Patients will then be randomised in a 2:1 ratio to receive anaerobically prepared stool or placebo for 8 weeks either by gastroscopy, or colonoscopy and enemas. Clinical response at 8 weeks (Crohn's Disease Activity Index (CDAI) reduction &#x2265;100 points or to <150 points) is the primary outcome measure. Non-responders to placebo and partial responders to FMT (CDAI decrease <100&#x2009;but >70) receive FMT for weeks 8-16.Patients achieving clinical response from FMT after 8 or 16 weeks will be randomised in a 1:1 ratio to either a 44-week maintenance phase of FMT or placebo. Patients will receive FMT from one donor throughout the study.The MIRO study will establish whether FMT is an effective and safe therapy to induce and maintain remission in patients with active Crohn's disease.<br><br>ETHICS AND DISSEMINATION: Ethical approval has been received by the St Vincent's Hospital Melbourne Human Research Ethics Committee (HREC-A 084/21). The results will be disseminated in peer-reviewed journals and presented at international conferences.<br><br>TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT04970446; Registered on 20 July 2021.}, }
@article {pmid40253186, year = {2025}, author = {Hao, Y and Wang, C and Wang, L and Hu, L and Duan, T and Zhang, R and Yang, X and Li, T}, title = {Nondigestible stachyose alleviates cyclophosphamide-induced small intestinal mucosal injury in mice by regulating intestinal exosomal miRNAs, independently of the gut microbiota.}, journal = {Food research international (Ottawa, Ont.)}, volume = {209}, number = {}, pages = {116258}, doi = {10.1016/j.foodres.2025.116258}, pmid = {40253186}, issn = {1873-7145}, mesh = {Animals ; *Cyclophosphamide/adverse effects/toxicity ; *Gastrointestinal Microbiome/drug effects ; *MicroRNAs/metabolism/genetics ; *Intestinal Mucosa/drug effects/pathology/metabolism ; *Oligosaccharides/pharmacology ; Mice ; *Intestine, Small/drug effects/pathology/metabolism ; *Exosomes/metabolism/drug effects/genetics ; Male ; Oxidative Stress/drug effects ; Mice, Inbred C57BL ; Cytokines/metabolism ; Prebiotics ; Permeability ; Germ-Free Life ; Tight Junction Proteins/metabolism ; }, abstract = {Stachyose has traditionally been considered to exert prebiotic effects primarily through its interaction with gut microbiota. However, this study reveals a novel mechanism by which stachyose alleviates cyclophosphamide (CY)-induced small intestinal mucosa disruption by regulating the intestinal exosomal miRNAs, without relying on the gut microbiota. Specifically, stachyose significantly mitigates CY-caused damage to the intestinal permeability, oxidative stress, and the structure of intestinal villi and crypts in pseudo-germ-free (PGF) mice. The immunofluorescence staining and qPCR analyses show that stachyose treatment restores CY-caused abnormal changes on the levels of tight junction proteins including MUC2, Occludin, Claudin-1, and ZO-1, and pro-inflammatory cytokines including TNF-α, IL-1β, and IL-2. Furthermore, by conducting fecal miRNA transplantation experiment, we further demonstrated that, similar to stachyose, stachyose-shaped intestinal miRNAs protect against CY-induced intestinal mucosal damage in PGF mice. In summary, this study provides new scientific evidence for the direct interaction between nondigestible stachyose and the proximal small intestine. It also opens new avenues for further investigation into the systemic nutritional functions of stachyose, particularly the health benefits of stachyose in the upper gastrointestinal tract.}, }
@article {pmid40253185, year = {2025}, author = {Yang, H and Zhao, Y and Zhang, R and Zhao, L and Yang, H and Liao, X}, title = {CiLi (Rosa roxburghii Tratt.) polyphenols improve colitis via gut microbiota-lipid mediator-immunity axis.}, journal = {Food research international (Ottawa, Ont.)}, volume = {209}, number = {}, pages = {116257}, doi = {10.1016/j.foodres.2025.116257}, pmid = {40253185}, issn = {1873-7145}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Polyphenols/pharmacology ; *Colitis/drug therapy/chemically induced/microbiology/immunology ; Mice ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Dextran Sulfate ; Dysbiosis ; Male ; Lipid Metabolism/drug effects ; Disease Models, Animal ; Colon/drug effects ; Fatty Acids, Volatile ; }, abstract = {Dysbiosis of gut microbiome is one of the most important factors leading to inflammatory bowel disease (IBD). Intake of phytochemicals from fruits and vegetables is an effective way to improve IBD, but how these bioactivators regulate gut microbiota to exert healthy effects remains unclear. Here, we found that pretreatment with CiLi juice, particularly its polyphenol component, alleviated dextran sulfate sodium (DSS)-induced colitis while preserving intestinal barrier integrity. CiLi polyphenols (CL_PP) reduced inflammation and oxidative stress in colon tissue and enriched fecal short-chain fatty acids. Importantly, CL_PP significantly regulated the gut microbiome diversity, increasing beneficial bacteria (e.g., Clostridia_UCG-014, f_Muribaculaceae and Ileibacterium_valens) while decreasing harmful bacteria (Escherichia-Shigella and Romboutsia). Multiomics analysis revealed that CL_PP upregulated bioactive lipid metabolites, particularly those derived from polyunsaturated fatty acids (e.g., resolvin D2, prostaglandin A1, and glycerophosphocholine) related gene expressions (Pltp, Alox15 and Pld4). Additionally, CL-PP downregulated the oxidative stress markers (oxidized glutathione and glutathione peroxidase 3), and immune cell markers (CD8 and CD68). Fecal microbiota transplantation confirmed that the fecal microbiota from CL_PP-treated mice exhibited anti-colitis effects. These effects were diminished in antibiotic-treated mice, underscoring the importance of the gut microbiota in mediating the CL_PP's anti-inflammatory benefits. This study suggests that CL_PP is a potential modulator of gut microbiome dysbiosis for the prevention and treatment of colitis.}, }
@article {pmid40253128, year = {2025}, author = {Zuo, G and Li, M and Guo, X and Wang, L and Yao, Y and Huang, JA and Liu, Z and Lin, Y}, title = {Fu brick tea supplementation ameliorates non-alcoholic fatty liver disease and associated endotoxemia via maintaining intestinal homeostasis and remodeling hepatic immune microenvironment.}, journal = {Food research international (Ottawa, Ont.)}, volume = {209}, number = {}, pages = {116207}, doi = {10.1016/j.foodres.2025.116207}, pmid = {40253128}, issn = {1873-7145}, mesh = {*Non-alcoholic Fatty Liver Disease/immunology ; Animals ; *Endotoxemia ; Gastrointestinal Microbiome/drug effects ; Male ; Humans ; Homeostasis/drug effects ; *Tea/chemistry ; *Liver/immunology/drug effects/metabolism ; Rats ; Diet, High-Fat/adverse effects ; Caco-2 Cells ; Dysbiosis ; Rats, Sprague-Dawley ; *Dietary Supplements ; Intestines ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a prevalent disorder of excessive fat accumulation and inflammation in the liver that currently lacks effective therapeutic interventions. Fu brick tea (FBT) has been shown to ameliorate liver damage and modulate gut microbiota dysbiosis in NAFLD, but the potential mechanisms have not been comprehensively elucidated, especailly whether its hepatoprotective effects are determined to depend on the homeostasis of gut microbiota, intestinal barrier function and hepatic immune microenvironment. In this study, our results further demonstrated that FBT not only alleviated NAFLD symptoms and related endotoxemia in high-fat diet (HFD)-fed rats, but also attenuated intestinal barrier dysfunction and associated inflammation, also confirmed in Caco-2 cell experiment. Meanwhile, FBT intervention significantly relieved HFD-induced gut microbiota dysbiosis, characterized by increased diversity and composition, particularly facilitating beneficial microbes, including short chain fatty acids (SCFAs) and bile acids producers, such as Blautia and Fusicatenibacter, and inhibiting Gram-negative bacteria, such as Prevotella_9 and Phascolarctobacterium. Also, the gut microbiota-dependent hepatoprotective effects of FBT were verified by fecal microbiota transplantation (FMT) experiment. Thus, the beneficial moulation of gut microbiota altered by FBT in levels of SCFAs, bile acids and lipopolysaccharides, intestinal barrier function and TLR4/NF-κB pathway contributed to alleviate liver steatosis and inflammation. Additionally, the hepatoprotective effects of FBT was further demonstrated by suppressing Kupffer cell activation and regulating lipid metabolism using an ex vivo model of liver organoid. Therefore, FBT supplementation can maintain intenstinal homeostasis and remodel hepatic immune microenvironment to prevent NAFLD and associated endotoxemia.}, }
@article {pmid40252900, year = {2025}, author = {Sahebi, K and Arianejad, M and Azadi, S and Hosseinpour-Soleimani, F and Kazemi, R and Tajbakhsh, A and Negahdaripour, M}, title = {The interplay between gut microbiome, epigenetics, and substance use disorders: from molecular to clinical perspectives.}, journal = {European journal of pharmacology}, volume = {998}, number = {}, pages = {177630}, doi = {10.1016/j.ejphar.2025.177630}, pmid = {40252900}, issn = {1879-0712}, abstract = {Substance use disorders (SUDs) involve a complex series of central and peripheral pathologies, leading to impairments in cognitive, behavioral, and physiological processes. Emerging evidence indicates a more significant role for the microbiome-gut-brain axis (MGBA) in SUDs than previously recognized. The MGBA is interconnected with various body systems by producing numerous metabolites, most importantly short-chain fatty acids (SCFAs), cytokines, and neurotransmitters. These mediators influence the human body's epigenome and transcriptome. While numerous epigenetic alterations in different brain regions have been reported in SUD models, the intricate relationship between SUDs and the MGBA suggests that the gut microbiome may partially contribute to the underlying mechanisms of SUDs. Promising results have been observed with gut microbiome-directed interventions in patients with SUDs, including prebiotics, probiotics, antibiotics, and fecal microbiota transplantation. Nonetheless, the long-term epigenetic effects of these interventions remain unexplored. Moreover, various confounding factors and study limitations have hindered the identification of molecular mechanisms and clinical applications of gut microbiome interventions in SUDs. In the present review, we will (i) provide a comprehensive discussion on how the gut microbiome influences SUDs, with an emphasis on epigenetic alterations; (ii) discuss the current evidence on the bidirectional relationship of gut microbiome and SUDs, highlighting potential targets for intervention; and (iii) review recent advances in gut microbiome-directed therapies, along with their limitations and future directions.}, }
@article {pmid40252828, year = {2025}, author = {Zhao, Y and Zhao, W and Chai, X and Sun, P and Huang, J and Guo, X and Zhang, L and Ren, D and Yi, C and Zhu, X and Zhao, S}, title = {Reshaping the gut microbiota: A novel oppinion of Eucommiae cortex polysaccharide alleviate learning and memory impairments in Alzheimer's disease.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.04.025}, pmid = {40252828}, issn = {2090-1224}, abstract = {BACKGROUND: Alzheimer's disease (AD), which is a chronic neurodegenerative disorder, is marked by the progressive deteriorations in learning and memory capabilities. The microbiota-gut-brain axis has come to be regarded as a crucial element in relation to the pathogenesis as well as the treatment of AD. Eucommiae cortex polysaccharides (EPs), being among the most plentiful substances present in the Eucommiae cortex, show the potential to exert immunomodulatory and neuroprotective function. However, whether EPs are protective against AD and their mechanism of action remain to be investigated OBJECTIVES: We hypothesize that EPs can regulate brain glutamine metabolism through gut microbiota and the butyric acid metabolized by them, improve oxidative stress and autophagy in the brain, and thus alleviate AD.<br><br>METHODS: In the present study, we used EPs (0.25&#xa0;% w/w in food) and fecal microbiota transplantation, as well as butyrate supplementation (0.1&#xa0;M in water), to intervene in AD mice. Multi-omics were used to determine the mechanism by which EPs improve AD-related learning and memory impairments.<br><br>RESULTS: Our results suggest that EPs, functioning as a prebiotic, alleviated learning and memory impairments in AD mice. Mechanistically, EPs are able to reshape the gut microbiota, promote the growth of gut microbiota involved in short-chain fatty acid metabolism, particularly butyrate-producing microbes. The butyrate produced by these microbes improves the brain microenvironment by modulating oxidative stress and autophagy mediated by brain glutamate metabolism, improving learning and memory impairments in AD mice, and inhibiting the formation and deposition of beta-amyloid proteins. Fecal microbiota transplantation (FMT) and butyrate supplementation further confirm this conclusion.<br><br>CONCLUSIONS: Our results highlighted that EPs can alleviate learning and memory impairments in AD with a gut microbiota-dependent manner and that butyric acid metabolized by butyric acid-metabolizing bacteria in the gut plays a central role in regulating brain glutamine metabolism to improve brain microenvironmental homeostasis. Meanwhile, the present study provides new insights into the treatment of AD with natural products.}, }
@article {pmid40252432, year = {2025}, author = {Wang, R and Gan, C and Gong, B and Huang, J and Lou, Z and Wang, D and Yan, R and Li, G and Xiong, T and Guo, J}, title = {Tongfu Xingshen capsule alleviates stroke-associated pneumonia-induced multiple organ injuries by modulating the gut microbiota and sphingolipid metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {142}, number = {}, pages = {156756}, doi = {10.1016/j.phymed.2025.156756}, pmid = {40252432}, issn = {1618-095X}, abstract = {BACKGROUND: Stroke-associated pneumonia (SAP) represents a major complication and cause of death in patients suffering from intracerebral haemorrhage (ICH). It's urgent to develop more effective therapeutic strategies. Tongfu Xingshen capsule (TFXS) is a traditional Chinese medicine that has been utilised in clinical studies for the treatment of ICH and SAP, but the underlying mechanisms remain to be fully elucidated.<br><br>PURPOSE: This study aims to explore the therapeutic effects and mechanisms of TFXS on SAP using an aspiration-induced Klebsiella pneumoniae infection-complicating ICH rat model and an intratracheal injection of lipopolysaccharide (LPS)-induced acute lung injury-complicating ICH rat model.<br><br>METHODS: The chemical components of TFXS are characterised using ULPLC-Q Exactive-Orbitrap-MS. The therapeutic effects of TFXS are evaluated through neurological scoring, histopathology analysis, magnetic resonance imaging, immunofluorescence, Alcian blue-nuclear fast red staining, myeloperoxidase activity assessment, leukocyte counting, and ELISA. To investigate the underlying mechanisms, faecal microbiota transplantation, 16S rRNA sequencing, untargeted metabolomics, and Spearman correlation analyses are performed.<br><br>RESULTS: A total of 60 compounds are identified in TFXS. Pharmacological analysis reveals that TFXS significantly mitigates neurological deficits, enhances haematoma absorption, attenuates brain damage and neuroinflammation, and improves pneumonia and pulmonary injury by reducing the infiltration of leukocytes and lymphocytes, as well as suppressing the infiltration and overactivation of neutrophils. TFXS also alleviates intestinal lesions and barrier damage by increasing acidic mucins and the expression of the tight junction protein zonula occludens-1 (ZO-1). Mechanistically, TFXS ameliorates pneumonia and pulmonary injury in a gut microbiota-dependent manner. It reverses sphingolipid metabolism disorders and ceramide accumulation by modulating SAP-induced gut microbiota dysbiosis and enhancing the abundance of probiotics, including Lactobacillus, Allobaculum and Enterococcus.<br><br>CONCLUSION: TFXS exerts anti-inflammatory and protective effects on the brain, lung, and gut by alleviating gut microbiota dysbiosis and sphingolipid metabolism disorders. These findings highlight TFXS as a promising therapeutic candidate for the treatment of SAP.}, }
@article {pmid40252102, year = {2025}, author = {Vassallo, GA and Dionisi, T and De Vita, V and Augello, G and Gasbarrini, A and Pitocco, D and Addolorato, G}, title = {The role of fecal microbiota transplantation in diabetes.}, journal = {Acta diabetologica}, volume = {}, number = {}, pages = {}, pmid = {40252102}, issn = {1432-5233}, abstract = {Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy for modulating gut dysbiosis in diabetes mellitus. This review critically evaluates preclinical and clinical evidence on FMT in type 1 (T1D) and type 2 diabetes (T2D). Studies suggest that FMT can restore microbial diversity, improve glycemic control, and modulate immune responses, with varying effects across diabetes subtypes. In T1D, preclinical models demonstrate that FMT influences regulatory T-cell expansion and β-cell preservation, though clinical translation remains limited. In T2D, FMT has shown transient improvements in insulin sensitivity, with sustained effects observed only in patients with specific microbiome signatures. However, heterogeneity in patient responses, donor variability, and methodological limitations complicate its clinical application. This review highlights the interplay between FMT, immune modulation, and microbial metabolism, advocating for phenotype-stratified trials and multi-omics integration to enhance therapeutic precision.}, }
@article {pmid40251524, year = {2025}, author = {Pan, Q and Guo, F and Chen, J and Huang, H and Huang, Y and Liao, S and Xiao, Z and Wang, X and You, L and Yang, L and Huang, X and Xiao, H and Liu, HF and Pan, Q}, title = {Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr mice.}, journal = {Cellular &amp; molecular biology letters}, volume = {30}, number = {1}, pages = {49}, pmid = {40251524}, issn = {1689-1392}, support = {82070757//National Natural Science Foundation of China/ ; 82270770//National Natural Science Foundation of China/ ; 82400841//National Natural Science Foundation of China/ ; 2022B1212030003//Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases/ ; 2022A1515220028//Guangdong Basic and Applied Basic Research Foundation Enterprise Joint Fund/ ; 2021A05060//Zhanjiang Science and Technology Project (Competitive)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice, Inbred MRL lpr ; *Mesenchymal Stem Cell Transplantation/methods ; *Lupus Erythematosus, Systemic/therapy/microbiology ; Mice ; Fecal Microbiota Transplantation ; Humans ; Mesenchymal Stem Cells/cytology/metabolism ; Female ; Disease Models, Animal ; Receptors, Aryl Hydrocarbon/metabolism ; Cytokines/metabolism ; }, abstract = {BACKGROUND: Systemic lupus erythematosus (SLE), influenced by gut microbiota dysbiosis, is characterized by autoimmune and inflammatory responses. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation is an effective and safe treatment for refractory or severe SLE; however, the long-term efficacy and mechanisms of early hUC-MSC therapeutic benefits in SLE need further investigation.<br><br>METHODS: Here, lupus-prone MRL/MpJ-Fas[lpr] (MRL/lpr) mice were divided into three groups: the control (Ctrl) group received saline injections, while the MSC and MSC-fecal microbiota transplantation (FMT) groups received early hUC-MSC transplants at weeks 6, 8, and 10. The MSC-FMT group also underwent FMT from the Ctrl group between weeks 9 and 13.<br><br>RESULTS: Our results showed that early MSC treatment extended therapeutic effects up to 12&#xa0;weeks, reducing autoantibodies, proinflammatory cytokines, B cells, and improving lupus nephritis. It also modulated the gut microbiota, increasing the abundance of beneficial bacteria, such as Lactobacillus johnsonii and Romboutsia ilealis, which led to higher levels of plasma tryptophan and butyrate metabolites. These metabolites activate the aryl hydrocarbon receptor (AHR), upregulate the Cyp1a1 and Cyp1b1 gene, enhance the zonula occludens 1 (ZO-1) protein, promote intestinal repair, and mitigate SLE progression. Notably, FMT from lupus mice significantly reversed hUC-MSC benefits, suggesting that the modulation of the gut microbiota plays a crucial role in the therapeutic response observed in MRL/lpr mice.<br><br>CONCLUSIONS: This research innovatively explores the early therapeutic window for MSCs in SLE, highlighting the partial mechanisms through which hUC-MSCs modulate the gut microbiota-tryptophan-AHR axis, thereby ameliorating SLE symptoms.}, }
@article {pmid40250802, year = {2025}, author = {Hirai, J}, title = {Extended-pulsed fidaxomicin therapy for recurrent Clostridioides difficile infection after standard vancomycin and fidaxomicin failure: A case report.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {31}, number = {6}, pages = {102709}, doi = {10.1016/j.jiac.2025.102709}, pmid = {40250802}, issn = {1437-7780}, abstract = {Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea. Recurrence occurs in up to 60 % of patients following multiple episodes, posing a major clinical challenge. While vancomycin (VCM) and fidaxomicin (FDX) are recommended first-line therapies, treatment failures and recurrences are not uncommon. Extended-pulsed fidaxomicin (EPFX) has been proposed to reduce recurrence, especially in high-risk patients, though the evidence remains limited for those with multiple prior relapses. We report the case of a 66-year-old man with advanced esophageal and gastric cancer who experienced four episodes of recurrent CDI despite standard treatment with VCM and FDX. Given the unavailability of bezlotoxumab (BEZ) in Japan and the limited accessibility of fecal microbiota transplantation (FMT), EPFX was selected as a salvage regimen. After both EPFX and pulse-tapered oral VCM were explained, the patient and physician elected to initiate EPFX, consisting of 200 mg twice daily for five days followed by 200 mg every other day for 20 days. No further recurrences were observed for over four months, and no adverse effects were noted. This case supports the use of EPFX in patients with multiple high-risk features-including advanced age, active malignancy, and prior treatment failures-despite the EXTEND trial's exclusion of patients with ≥3 recurrences. The favorable pharmacokinetic properties of FDX may have contributed to its efficacy. Importantly, the patient's medication, nutritional, and oncologic status remained stable throughout treatment, suggesting that EPFX played a pivotal role in achieving remission. EPFX may offer a viable option for patients with recurrent CDI refractory to standard therapies.}, }
@article {pmid40248060, year = {2025}, author = {Liu, HJ and Wu, MC and Gau, SY}, title = {Role of gut microbiota and mesenteric adipose tissue in the pathology of Crohn's disease: Potential therapeutic targets.}, journal = {World journal of gastroenterology}, volume = {31}, number = {13}, pages = {102291}, pmid = {40248060}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/physiology ; *Crohn Disease/microbiology/therapy/pathology/immunology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Adipose Tissue/pathology ; Treatment Outcome ; Mesentery/pathology ; Colitis, Ulcerative/microbiology/therapy/immunology/pathology ; Remission Induction ; Animals ; Intestinal Mucosa/microbiology/pathology/immunology ; Dysbiosis/therapy/immunology/microbiology ; }, abstract = {This editorial comments on the article by Wu et al in the World Journal of Gastroenterology. The article explored the relationship between mesenteric adipose tissue, creeping fat, inflammation, and gut microbiota in Crohn's disease (CD). We discussed three key aspects of the interaction between gut microbiota and inflammatory bowel disease (IBD): The physiological functions of the gut microbiota, the potential role of probiotics in IBD treatment; and the effect of fecal microbiota transplantation (FMT) in combating IBD. IBD, comprising CD and ulcerative colitis (UC), is influenced by the gut microbiota. Changes in gut microbiota composition disrupt intestinal function and promote chronic inflammation, but the exact mechanisms remain unclear. Probiotics have demonstrated some efficacy in inducing remission in UC, though their effectiveness in CD is still debated. FMT shows promise in treating IBD, especially UC, by restoring gut microbiota diversity and inducing clinical remission. As for CD, FMT has potential, but more studies are needed to confirm its long-term effectiveness and safety. Dietary approaches may help manage IBD symptoms or disease activity, but patient adherence is crucial. Clinicians and researchers must recognize the importance of the gut microbiota and the need for personalized therapies targeting microbial imbalances.}, }
@article {pmid40247656, year = {2025}, author = {Bonazzi, E and De Barba, C and Lorenzon, G and Maniero, D and Bertin, L and Barberio, B and Facciotti, F and Caprioli, F and Scaldaferri, F and Zingone, F and Savarino, EV}, title = {Recent developments in managing luminal microbial ecology in patients with inflammatory bowel disease: from evidence to microbiome-based diagnostic and personalized therapy.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/17474124.2025.2495087}, pmid = {40247656}, issn = {1747-4132}, abstract = {INTRODUCTION: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic condition characterized by abnormal immune responses and intestinal inflammation. Emerging evidence highlights the vital role of gut microbiota in IBD's onset and progression. Recent advances have shaped diagnostic and therapeutic strategies, increasingly focusing on microbiome-based personalized care. Methodology: this review covers studies from 2004 to 2024, reflecting the surge in research on luminal microbial ecology in IBD. Human studies were prioritized, with select animal studies included for mechanistic insights. Only English-language, peer-reviewed articles - clinical trials, systematic reviews, and meta-analyses - were considered. Studies without clinical validation were excluded unless offering essential insights. Searches were conducted using PubMed, Scopus, and Web of Science.<br><br>AREAS COVERED: we explore mechanisms for managing IBD-related microbiota, including microbial markers for diagnosis and novel therapies such as fecal microbiota transplantation, metabolite-based treatments, and precision microbiome modulation. Additionally, we review technologies and diagnostic tools used to analyze gut microbiota composition and function in clinical settings. Emerging data supporting personalized therapeutic strategies based on individual microbial profiles are discussed.<br><br>EXPERT OPINION: Standardized microbiome research integration into clinical practice will enhance precision in IBD care, signaling a shift toward microbiota-based personalized medicine.}, }
@article {pmid40246750, year = {2025}, author = {Gefen, R and Dourado, J and Emile, SH and Wignakumar, A and Rogers, P and Aeschbacher, P and Garoufalia, Z and Horesh, N and Wexner, SD}, title = {Fecal microbiota transplantation for patients with ulcerative colitis: a systematic review and meta-analysis of randomized control trials.}, journal = {Techniques in coloproctology}, volume = {29}, number = {1}, pages = {103}, pmid = {40246750}, issn = {1128-045X}, mesh = {Humans ; *Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation/methods/adverse effects ; Randomized Controlled Trials as Topic ; Remission Induction/methods ; Treatment Outcome ; Male ; Female ; Adult ; Middle Aged ; Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to restore gut microbiome composition with an acceptable safety profile. FMT in inflammatory bowel disease, specifically ulcerative colitis (UC), has been investigated. We aimed to assess the efficacy of FMT in inducing UC remission.<br><br>METHODS: PubMed, Scopus, Google Scholar, and clinicaltrials.gov were searched for randomized control trials that assessed FMT in inducing UC remission. The primary outcome was combined clinical and endoscopic remission. Secondary outcomes were clinical remission, endoscopic remission, post-treatment overall adverse events, and colitis. Sensitivity analyses, meta-regression, bias assessment, and grading of certainty of evidence were performed.<br><br>RESULTS: A total of 14 studies including 600 patients (55.8% male; median age 40.7&#xa0;years) were assessed. FMT was used in 299 patients and associated with significantly higher odds of combined clinical and endoscopic remission (OR 2.25,&#xa0;95% CI 1.54, 3.3; p&#x2009;<&#x2009;0.0001), clinical remission (OR 2.02,&#xa0;95% CI 1.4, 2.93; p&#x2009;=&#x2009;0.0002), and endoscopic remission (OR 1.95,&#xa0;95% CI 1.17, 3.28; p&#x2009;=&#x2009;0.011). The odds of post-treatment overall adverse events (OR 1.24,&#xa0;95% CI 0.79, 1.95; p&#x2009;=&#x2009;0.34) and colitis (OR 0.85,&#xa0;95% CI 0.52, 1.93; p&#x2009;=&#x2009;0.512) were similar between groups. Compared with baseline, FMT was more effective when biologics (OR 2.71), steroids (OR 2.27), or methotrexate (OR 3.07) were used as pre-FMT treatment. Oral delivery of FMT (OR 3.15) and pooled donors (OR 3.32) led to higher odds of remission. On meta-regression, pooled donors and methotrexate pre-treatment were associated with an increased likelihood of remission.<br><br>CONCLUSIONS: FMT is promising in inducing UC remission. Administration of medical treatments before FMT may help achieve higher remission rates. Current evidence shows that oral delivery of FMT and multidonor FMT may confer better results.}, }
@article {pmid40246463, year = {2025}, author = {Xia, S and Yan, C and Cai, G and Xu, Q and Zou, H and Gu, J and Yuan, Y and Liu, Z and Bian, J}, title = {Gut dysbiosis exacerbates inflammatory liver injury induced by environmentally relevant concentrations of nanoplastics via the gut-liver axis.}, journal = {Journal of environmental sciences (China)}, volume = {155}, number = {}, pages = {250-266}, doi = {10.1016/j.jes.2024.11.022}, pmid = {40246463}, issn = {1001-0742}, mesh = {Animals ; *Dysbiosis/chemically induced ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Microplastics/toxicity ; Liver/drug effects ; *Environmental Pollutants/toxicity ; *Chemical and Drug Induced Liver Injury ; Inflammation/chemically induced ; Male ; *Nanoparticles/toxicity ; }, abstract = {As an emerging and potentially threatening pollutant, nanoplastics (NPs) have received considerable global attention. Due to their physical properties and diminutive size, NPs ingestion can more easily cross biological barriers and enter the human and animal body. Despite reports of hepatotoxicity associated with NPs, their impact and potential underlying mechanisms remain elusive. In this study, we investigated the impact of NPs at concentrations found in the environment on the gut flora, intestinal barrier function, liver pyroptosis, and inflammation in mice following 12 weeks of exposure. To further validate the involvement of gut flora in inflammatory liver damage caused by NPs, we utilized antibiotics to remove the intestinal flora and performed fecal microbiota transplantation. We confirmed that NPs exposure altered the gut microbiota composition, with a notable rise in the proportions of Alloprevotella and Ileibacterium while causing a decrease in the relative proportions of Dubosiella. This disruption also affected the gut barrier, increasing lipopolysaccharides in circulation and promoting liver pyroptosis. Importantly, mice receiving fecal transplants from NPs-treated mice showed intestinal barrier damage, liver pyroptosis, and inflammation. However, NPs effects on the intestinal barrier and liver pyroptosis were attenuated by antibiotics depletion of the commensal microbiota. In summary, our current research revealed that extended exposure to environmentally relevant concentrations of NPs resulted in inflammatory damage to the liver. Additionally, we have identified for the first time that imbalances in intestinal flora are crucial in liver pyroptosis induced by NPs.}, }
@article {pmid40246176, year = {2025}, author = {Adıgüzel, E and Yılmaz, &#x15e;G and Atabilen, B and Şeref, B}, title = {Microbiome modulation as a novel therapeutic modality for anxiety disorders: A review of clinical trials.}, journal = {Behavioural brain research}, volume = {487}, number = {}, pages = {115595}, doi = {10.1016/j.bbr.2025.115595}, pmid = {40246176}, issn = {1872-7549}, mesh = {Humans ; *Anxiety Disorders/microbiology/physiopathology/therapy ; Clinical Trials as Topic ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; Synbiotics/administration &amp; dosage ; }, abstract = {Anxiety disorders are one of the major conditions in psychiatry characterized by symptoms such as worry, social and performance fears, unexpected and/or triggered panic attacks, anticipatory anxiety, and avoidance behaviors. Recent developments have drawn attention to the putative involvement of peripheral systems in the control of anxiety, and the gut microbiota has come to light as an emerging peripheral target for anxiety. The relationship between the gut-brain axis, a bidirectional communication network between the central nervous system (CNS) and enteric nervous system (ENS), and anxiety has been the subject of some recent studies. Therefore, this systematic review analyzed clinical trials evaluating the potential of microbiome modulation methods in mitigating and ameliorating anxiety disorders. Clinical studies on probiotic, prebiotic, synbiotic supplements, dietary interventions, and fecal microbiota transplantation in anxiety disorders were screened. All of the studies examined the effects of probiotic intervention. One of these studies compared a prebiotic-rich diet with probiotic supplementation. Longitudinal analyses showed that the probiotic intervention alleviated anxiety. However, most of the controlled studies reported that the probiotic intervention did not make a difference compared to placebo. Thus, the current findings suggest that it is too early to consider the promising role of microbiome modulation in the treatment of anxiety disorders. However, it is obvious that more clinical research is needed to clarify issues such as probiotic strains, prebiotic types, and their doses that may be effective on anxiety disorders.}, }
@article {pmid40245946, year = {2025}, author = {Vinit, N and Glenisson, M and Leroy, J and Sarnacki, S and Crétolle, C and Beaudoin, S}, title = {Anatomical Correction and Early Outcomes of One-step Ventral and Dorsal Proctoplasty in Girls with Low Anorectal Malformations.}, journal = {European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2590-5697}, pmid = {40245946}, issn = {1439-359X}, abstract = {Rectoperineal fistula (RPF) and rectovestibular fistula (RVF) are the most common forms of low anorectal malformations (ARMs) in girls, and lead to difficult stooling, thus demanding early surgical correction. This study's aim was to assess early outcomes associated with one-step ventral and dorsal proctoplasty in RPF/RVF.All female infants who consecutively underwent one-step proctoplasty for RPF/RVF at our institution (2012-2022) were retrospectively included. Reviewed data included: age at procedure, congenital anomalies, fistula location, preoperative symptoms, intraoperative findings, operative time, postoperative complications, and bowel functional outcome. Success of the technique, defined as spontaneous bowel movement at last follow-up without anal dilation, was assessed. Secondary outcomes included resolution of preoperative symptoms, and Krickenbeck score and fecal continence in girls older than 3 years at last follow-up. No preoperative bowel preparation was necessary.None of the 77 included girls (median age at surgery: 3.2 months (2.3-7.3)) had prior colostomy. In every case, intraoperative findings included: ventral defect of the external anal sphincter, and abnormal attachment of the bulbospongiosus muscles to the fistula and posterior ledge, thus justifying both ventral and dorsal reconstructions. The median operative time was 34 min (27-38), and the median hospital stay was 2 days (2-3). Limited ventral skin dehiscence was the most common postoperative complication (31%), with limited effect on clinical outcome (one secondary anal stricture). No child required secondary colostomy or revision anoplasty. One child underwent secondary pull-through due to persistent megarectum. Preoperative symptoms resolved in 98% of cases. After a median follow-up of 27.6 months (9.8-48.3), all girls had spontaneous bowel movement and 21% had grade-2 constipation. The technique was successful in 97% of cases (two anal strictures treated with dilations).RPF/RVF in female share abnormal anatomical characteristics. One-step ventral and dorsal proctoplasty allows precise anatomical correction of low ARM in girls.}, }
@article {pmid40245774, year = {2025}, author = {Zhang, X and Yin, Y and Chen, Y and Lin, L and Shen, S and Fang, F and Wang, Q}, title = {Gut microbiota contributes to obstructive sleep apnea-induced hypertension by gut-heart axis in mice.}, journal = {International immunopharmacology}, volume = {155}, number = {}, pages = {114667}, doi = {10.1016/j.intimp.2025.114667}, pmid = {40245774}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Sleep Apnea, Obstructive/complications/microbiology ; *Hypertension/microbiology/etiology ; Male ; Toll-Like Receptor 4/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; *Dysbiosis/microbiology ; Mice ; Humans ; NF-kappa B/metabolism ; Lipopolysaccharides/metabolism ; Signal Transduction ; Blood Pressure ; }, abstract = {BACKGROUND: The gut microbiome has been closely linked to obstructive sleep apnea (OSA)-associated hypertension (HTN). However, its precise role in the pathogenesis of OSA-induced HTN remains unclear.<br><br>METHODS: To clarify the causal relationship between gut dysbiosis and OSA-related HTN, C57BL6J mice were randomly assigned to four groups. Each group underwent fecal microbiota transplantation from healthy individuals (control), OSA patients (OSA group), OSA patients with pre-hypertension (OSA-pHTN group), or OSA patients with HTN (OSA-HTN group). The pro-hypertensive effects of the OSA gut microbiota were verified, and the composition and function of the gut microbiota were compared using 16S rDNA gene sequencing. Additionally, the gut microbiota-related lipopolysaccharide (LPS)/ Toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-&#x3ba;B) pathway in aortic tissues was investigated.<br><br>RESULTS: Fecal microbiota transplantation induced increased systolic blood pressure and aortic injury in mice from the OSA, OSA-pHTN and OSA-HTN groups, whereas no significant injury was observed in the control group. These three groups exhibited dysbiosis and impaired intestinal barrier function as evidenced by a reduction in Akkermansia and decreased expression of zonula occludens-1 and Occludin proteins. In addition, LPS, TLR4 and phosphorylated NF-&#x3ba;B expression were increased in aortic tissue from the three groups, and immunofluorescence showed a significant upregulation of TLR4 expression in aortic endothelial cells compared to controls.<br><br>CONCLUSION: This study demonstrates the pro-hypertensive effects of gut microbiota in OSA, mediated through the gut-derived LPS/TLR4/NF-&#x3ba;B pathway. These findings may guide the development of therapeutic strategies focused on restoring gut microbiome homeostasis.}, }
@article {pmid40244948, year = {2025}, author = {Zhou, H and Zhuang, Y and Liang, Y and Chen, H and Qiu, W and Xu, H and Zhou, H}, title = {Curcumin exerts anti-tumor activity in colorectal cancer via gut microbiota-mediated CD8[+] T Cell tumor infiltration and ferroptosis.}, journal = {Food &amp; function}, volume = {16}, number = {9}, pages = {3671-3693}, doi = {10.1039/d4fo04045g}, pmid = {40244948}, issn = {2042-650X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Curcumin/pharmacology/administration &amp; dosage ; Mice ; *Colorectal Neoplasms/drug therapy/immunology/microbiology ; *CD8-Positive T-Lymphocytes/drug effects/immunology ; Humans ; *Ferroptosis/drug effects ; Cell Line, Tumor ; Male ; *Antineoplastic Agents/pharmacology ; Mice, Inbred BALB C ; Apoptosis/drug effects ; }, abstract = {Colorectal cancer (CRC), as a high-incidence malignancy, continues to present significant challenges in prevention, screening, and treatment. Curcumin (Cur) exhibits notable anti-inflammatory and anticancer properties. Despite its poor solubility in water and low bioavailability, high concentrations of Cur are detected in the gastrointestinal tract after oral administration, suggesting that it may directly interact with the gut microbiota and exert regulatory effects. This study aims to explore the mechanisms by which Cur improves CRC by modulating gut microbiota. Firstly, we evaluated the effect of Cur on CRC cell viability in vitro using the MTT assay, and the results showed a significant inhibitory effect on CRC cell growth. The IC50 values for Cur in CT26 and RKO cells were 23.52 μM, 16.11 μM, and 13.62 μM at 24, 48, and 72 hours, respectively, and 26.3 μM, 16.52 μM, and 14.22 μM at 24, 48, and 72 hours, respectively. Cur induced apoptosis and caused G2 phase cell cycle arrest in tumor cells. Subsequently, we established a CRC mouse model. Oral administration of Cur at 15 mg kg[-1] and 30 mg kg[-1] inhibited CRC progression, as evidenced by reduced tumor volume, histological analysis, immunohistochemistry, and an increased number of CD8[+] T cells infiltrating the tumors. Ferroptosis in tumor cells was also observed. Cur partially restored the gut microbiota of CRC mice, altering the abundance and diversity of the gut microbiota and affecting serum metabolite distribution, with significant increases in the abundance of SCFA-producing microbes such as Lactobacillus and Kineothrix. To verify causality, we designed a fecal microbiota transplantation (FMT) experiment. Compared with CRC mice, the fecal microbiota from Cur-treated mice significantly alleviated CRC symptoms, including slowed tumor growth, enhanced CD8[+] T cell tumor infiltration, and induced ferroptosis in tumor cells. Additionally, when gut microbiota was depleted with antibiotics, Cur's antitumor effects disappeared, suggesting that Cur mitigates CRC in a gut microbiota-dependent manner. These findings provide new insights into the mechanisms underlying CRC and propose novel therapeutic interventions, emphasizing the interaction between gut microbiota and immune responses within the tumor immune microenvironment (TIME).}, }
@article {pmid40244415, year = {2025}, author = {Nista, EC and Parello, S and Brigida, M and Amadei, G and Saviano, A and De Lucia, SS and Petruzziello, C and Migneco, A and Ojetti, V}, title = {Exploring the Role of Gut Microbiota and Probiotics in Acute Pancreatitis: A Comprehensive Review.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40244415}, issn = {1422-0067}, mesh = {*Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Humans ; *Pancreatitis/microbiology/therapy ; Fecal Microbiota Transplantation ; Animals ; Acute Disease ; }, abstract = {Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology of AP is multifactorial and intricate, involving a cascade of events that lead to pancreatic injury and systemic inflammation. The progression of AP is influenced by many factors, including genetic predispositions, environmental triggers, and immune dysregulation. Recent studies showed a critical involvement of the gut microbiota in shaping the immune response and modulating inflammatory processes during AP. This review aims to provide a comprehensive overview of the emerging role of gut microbiota and probiotics in AP. We analyzed the implication of gut microbiota in pathogenesis of AP and the modification during an acute attack. The primary goals of microbiome-based therapies, which include probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and enteral nutrition, are to alter the composition of the gut microbial community and the amount of metabolites derived from the microbiota. By resetting the entire flora or supplementing it with certain beneficial organisms and their byproducts, these therapeutic approaches aim to eradicate harmful microorganisms, reducing inflammation and avoiding bacterial translocation and the potential microbiota-based therapeutic target for AP from nutrition to pre- and probiotic supplementation to fecal transplantation.}, }
@article {pmid40244136, year = {2025}, author = {Wu, Z and Yan, S and Zhang, H and Ma, Z and Du, R and Liu, Z and Li, X and Cao, G and Song, Y}, title = {Oral Sheep Milk-Derived Exosome Therapeutics for Cadmium-Induced Inflammatory Bowel Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40244136}, issn = {1422-0067}, support = {No. 2022JBGS0021//Inner Mongolia Autonomous Region "Jiebangguashuai" project of China/ ; No. 2022ZD0401403//The Scientific and Technological Innovation 2030 - major project funding/ ; 10000-23122101/021//2024 Inner Mongolia University "Steed Plan" high-level talent funding/ ; }, mesh = {Animals ; Mice ; *Exosomes/metabolism ; *Cadmium/toxicity ; Gastrointestinal Microbiome ; *Milk/chemistry ; Sheep ; *Inflammatory Bowel Diseases/therapy/chemically induced/etiology/microbiology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Administration, Oral ; }, abstract = {Cadmium (Cd) contamination in plants and soil poses significant risks to livestock, particularly sheep. Cd exposure often leads to severe gastrointestinal diseases in sheep that are difficult to treat. Milk-derived exosomes, particularly those from sheep milk (SM-Exo), have shown potential in treating gastrointestinal disorders, though their efficacy in Cd-induced colitis remains unclear. In this study, we investigated the therapeutic potential of SM-Exo in a Cd-induced colitis model. Hu sheep were exposed to Cd, and their fecal microbiota were collected to prepare bacterial solutions for fecal microbiota transplantation (FMT) in mice. The changes in gut microbiota and gene expression were analyzed through microbiome and transcriptomics. Our results showed that prior to treatment, harmful bacteria (e.g., Bacteroides and Parabacteroides) were increased in FMT mice. SM-Exo treatment increased beneficial bacteria, particularly Lachnoclostridium, and activated the Cyclic Adenosine Monophosphate (cAMP) pathway, upregulating genes like Adcy1, Adcy3, CREB, and Sst. These changes were linked to reduced Cd-induced cell death and alleviation of colonic inflammation. In conclusion, SM-Exo appears to be a promising treatment for Cd-induced colitis, likely through modulation of the gut microbiota and activation of the cAMP pathway.}, }
@article {pmid40243936, year = {2025}, author = {Ma, B and Barathan, M and Ng, MH and Law, JX}, title = {Oxidative Stress, Gut Microbiota, and Extracellular Vesicles: Interconnected Pathways and Therapeutic Potentials.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243936}, issn = {1422-0067}, support = {FF-2024-115/1//National University of Malaysia/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Oxidative Stress ; *Extracellular Vesicles/metabolism ; Animals ; Dysbiosis/metabolism ; Signal Transduction ; Reactive Oxygen Species/metabolism ; Antioxidants ; Probiotics/therapeutic use ; Inflammation ; }, abstract = {Oxidative stress (OS) and gut microbiota are crucial factors influencing human health, each playing a significant role in the development and progression of chronic diseases. This review provides a comprehensive analysis of the complex interplay between these two factors, focusing on how an imbalance between reactive oxygen species (ROS) and antioxidants leads to OS, disrupting cellular homeostasis and contributing to a range of conditions, including metabolic disorders, cardiovascular diseases, neurological diseases, and cancer. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, is essential for regulating immune responses, metabolic pathways, and overall health. Dysbiosis, an imbalance in the gut microbiota composition, is closely associated with chronic inflammation, metabolic dysfunction, and various diseases. This review highlights how the gut microbiota influences and is influenced by OS, complicating the pathophysiology of many conditions. Furthermore, emerging evidence has identified extracellular vesicles (EVs) as critical facilitators of cellular crosstalk between the OS and gut microbiota. EVs also play a crucial role in signaling between the gut microbiota and host tissues, modulating immune responses, inflammation, and metabolic processes. The signaling function of EVs holds promise for the development of targeted therapies aimed at restoring microbial balance and mitigating OS. Personalized therapeutic approaches, including probiotics, antioxidants, and fecal microbiota transplantation-based strategies, can be used to address OS-related diseases and improve health outcomes. Nonetheless, further research is needed to study the molecular mechanisms underlying these interactions and the potential of innovative interventions to offer novel strategies for managing OS-related diseases and enhancing overall human health.}, }
@article {pmid40243802, year = {2025}, author = {Xiong, Y and Guo, J and Yu, W and Zeng, D and Song, C and Zhou, L and Anatolyevna, NL and Baranenko, D and Xiao, D and Zhou, Y and Lu, W}, title = {Molecular Mechanism of Microgravity-Induced Intestinal Flora Dysbiosis on the Abnormalities of Liver and Brain Metabolism.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243802}, issn = {1422-0067}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Liver/metabolism/pathology ; *Brain/metabolism ; *Dysbiosis/metabolism/microbiology/etiology ; Mice ; *Weightlessness/adverse effects ; Male ; Space Flight ; Weightlessness Simulation/adverse effects ; Mice, Inbred C57BL ; Metabolomics/methods ; }, abstract = {Space flight has many adverse effects on the physiological functions of astronauts. Certain similarities have been observed in some physiological processes of rodents and astronauts in space, although there are also differences. These similarities make rodents helpful models for initial investigations into space-induced physiological changes. This study uses a 3D-Clinostat to simulate microgravity and explores the role of microgravity in space flight-induced liver and brain abnormalities by comparing changes in the gut microbiota, serum metabolites, and the function and physiological biochemistry of liver and brain tissues between the simulated microgravity (SMG) group mice and the wild type (WT) group mice. The study, based on hematoxylin-eosin (HE) staining, 16S sequencing technology, and non-targeted metabolomics analysis, shows that the gut tissue morphology of the SMG group mice is abnormal, and the structure of the gut microbiota and the serum metabolite profile are imbalanced. Furthermore, using PICRUST 2 technology, we have predicted the functions of the gut microbiota and serum metabolites, and the results indicate that the liver metabolism and functions (including lipid metabolism, amino acid metabolism, and sugar metabolism, etc.) of the SMG group mice are disrupted, and the brain tissue metabolism and functions (including neurotransmitters and hormone secretion, etc.) are abnormal, suggesting a close relationship between microgravity and liver metabolic dysfunction and brain dysfunction. Additionally, the high similarity in the structure of the gut microbiota and serum metabolite profile between the fecal microbiota transplant (FMT) group mice and the SMG group mice, and the physiological and biochemical differences in liver and brain tissues compared to the WT group mice, suggest that microgravity induces imbalances in the gut microbiota, which in turn triggers abnormalities in liver and brain metabolism and function. Finally, through MetaMapp analysis and Pearson correlation analysis, we found that valeric acid, a metabolite of gut microbiota, is more likely to be the key metabolite that relates to microgravity-induced gut microbiota abnormalities, disorders of amino acid and lipid metabolism, and further induced metabolic or functional disorders in the liver and brain. This study has significant practical application value for deepening the understanding of the adaptability of living organisms in the space environment.}, }
@article {pmid40243712, year = {2025}, author = {Murgiano, M and Bartocci, B and Puca, P and di Vincenzo, F and Del Gaudio, A and Papa, A and Cammarota, G and Gasbarrini, A and Scaldaferri, F and Lopetuso, LR}, title = {Gut Microbiota Modulation in IBD: From the Old Paradigm to Revolutionary Tools.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243712}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy/microbiology ; Fecal Microbiota Transplantation/methods ; Probiotics/therapeutic use ; Animals ; Prebiotics ; }, abstract = {Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders primarily comprising two main conditions: ulcerative colitis and Crohn's disease. The gut microbiota's role in driving inflammation in IBD has garnered significant attention, yet the precise mechanisms through which the microbiota influences IBD pathogenesis remain largely unclear. Given the limited therapeutic options for IBD, alternative microbiota-targeted therapies-including prebiotics, probiotics, postbiotics, and symbiotics-have been proposed. While these approaches have shown promising results, microbiota modulation is still mainly considered an adjunct therapy to conventional treatments, with a demonstrated impact on patients' quality of life. Fecal microbiota transplantation (FMT), already approved for treating Clostridioides difficile infection, represents the first in a series of innovative microbiota-based therapies under investigation. Microbial biotherapeutics are emerging as personalized and cutting-edge tools for IBD management, encompassing next-generation probiotics, bacterial consortia, bacteriophages, engineered probiotics, direct metabolic pathway modulation, and nanotherapeutics. This review explores microbial modulation as a therapeutic strategy for IBDs, highlighting current approaches and examining promising tools under development to better understand their potential clinical applications in managing intestinal inflammatory disorders.}, }
@article {pmid40243656, year = {2025}, author = {Li, X and Yang, W and Weng, Y and Zhao, Y and Chen, H and Chen, Y and Qiu, J and Jiang, B and Li, C and Lai, Y}, title = {Scutellarin Alleviates CCl4-Induced Liver Fibrosis by Regulating Intestinal Flora and PI3K/AKT Signaling Axis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243656}, issn = {1422-0067}, support = {No. 81360511//National Natural Science Foundation of China/ ; No.KY2319102140//Dali University Research and Development Fund/ ; }, mesh = {Animals ; *Apigenin/pharmacology/chemistry/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; *Glucuronates/pharmacology/chemistry ; *Proto-Oncogene Proteins c-akt/metabolism ; Male ; Rats ; *Phosphatidylinositol 3-Kinases/metabolism ; *Signal Transduction/drug effects ; *Liver Cirrhosis/drug therapy/chemically induced/metabolism/pathology ; Carbon Tetrachloride/toxicity ; Rats, Sprague-Dawley ; Molecular Docking Simulation ; }, abstract = {Liver fibrosis is a pathological manifestation of chronic liver disease developing to the terminal stage, and there is a lack of effective therapeutic drugs in clinical practice. Scutellarin (SCU) is a flavonoid extracted from Erigeron breviscapus (Vaniot.) Hand.-Mazz., which has significant anti-liver-fibrosis efficacy, but its mode of action remains incompletely understood. A liver fibrosis model was built with male Sprague Dawley rats induced with the disease by CCl4 to evaluate the therapeutic effect of drugs. 16S rRNA sequencing and metabolomics were used to analyze the regulatory effects of SCU on intestinal flora and host metabolism; antibiotics were administered to eliminate gut microbiota and fecal microbiota transplantation (FMT) experiments were used to verify the mechanism. The mechanistic basis underlying SCU's hepatic anti-fibrotic effects was screened by network pharmacology combined with transcriptomics, combined with molecular docking, qPCR, and WB verification. The results showed that SCU may play an anti-liver-fibrosis role by correcting the imbalance of gut flora and regulating the linoleic acid and purine metabolic pathways. In addition, SCU can downregulate the levels of proteins and genes related to the PI3K/AKT axis. In summary, SCU alleviates liver fibrosis by reversing intestinal flora imbalance, regulating the metabolic profile, and inhibiting the PI3K/AKT axis.}, }
@article {pmid40243472, year = {2025}, author = {Beyoğlu, D and Idle, JR}, title = {The Microbiome and Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243472}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; Dysbiosis/microbiology ; *Fatty Liver/microbiology/metabolism/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Liver/microbiology/metabolism/pathology ; Bile Acids and Salts/metabolism ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition wherein excessive fat accumulates in the liver, leading to inflammation and potential liver damage. In this narrative review, we evaluate the tissue microbiota, how they arise and their constituent microbes, and the role of the intestinal and hepatic microbiota in MASLD. The history of bacteriophages (phages) and their occurrence in the microbiota, their part in the potential causation of MASLD, and conversely, "phage therapy" for antibiotic resistance, obesity, and MASLD, are all described. The microbiota metabolism of bile acids and dietary tryptophan and histidine is defined, together with the impacts of their individual metabolites on MASLD pathogenesis. Both periodontitis and intestinal microbiota dysbiosis may cause MASLD, and how individual microorganisms and their metabolites are involved in these processes is discussed. Novel treatment opportunities for MASLD involving the microbiota exist and include fecal microbiota transplantation, probiotics, prebiotics, synbiotics, tryptophan dietary supplements, intermittent fasting, and phages or their holins and endolysins. Although FDA is yet to approve phage therapy in clinical use, there are multiple FDA-approved clinical trials, and this may represent a new horizon for the future treatment of MASLD.}, }
@article {pmid40243365, year = {2025}, author = {Ismeurt-Walmsley, C and Giannoni, P and Servant, F and Mekki, L-N and Baranger, K and Rivera, S and Marin, P and Lelouvier, B and Claeysen, S}, title = {The same but different: impact of animal facility sanitary status on a transgenic mouse model of Alzheimer's disease.}, journal = {mBio}, volume = {}, number = {}, pages = {e0400124}, doi = {10.1128/mbio.04001-24}, pmid = {40243365}, issn = {2150-7511}, abstract = {UNLABELLED: The gut-brain axis has emerged as a key player in the regulation of brain function and cognitive health. Gut microbiota dysbiosis has been observed in preclinical models of Alzheimer's disease and patients. Manipulating the composition of the gut microbiota enhances or delays neuropathology and cognitive deficits in mouse models. Accordingly, the health status of the animal facility may strongly influence these outcomes. In the present study, we longitudinally analyzed the fecal microbiota composition and amyloid pathology of 5XFAD mice housed in a specific opportunistic pathogen-free (SOPF) and a conventional facility. The composition of the microbiota of 5XFAD mice after aging in conventional facility showed marked differences compared to WT littermates that were not observed when the mice were bred in SOPF facility. The development of amyloid pathology was also enhanced by conventional housing. We then transplanted fecal microbiota (FMT) from both sources into wild-type (WT) mice and measured memory performance, assessed in the novel object recognition test, in transplanted animals. Mice transplanted with microbiota from conventionally bred 5XFAD mice showed impaired memory performance, whereas FMT from mice housed in SOPF facility did not induce memory deficits in transplanted mice. Finally, 18 weeks of housing SOPF-born animals in a conventional facility resulted in the reappearance of specific microbiota compositions in 5XFAD vs WT mice. In conclusion, these results show a strong impact of housing conditions on microbiota-associated phenotypes and question the relevance of breeding preclinical models in specific pathogen-free (SPF) facilities.<br><br>IMPORTANCE: Housing conditions affect the composition of the gut microbiota. Gut microbiota of 6-month-old conventionally bred Alzheimer's mice is dysbiotic. Gut dysbiosis is absent in Alzheimer's mice housed in highly sanitized facilities. Transfer of fecal microbiota from conventionally bred mice affects cognition. Microbiota of mice housed in highly sanitized facilities has no effect on cognition.}, }
@article {pmid40243343, year = {2025}, author = {Olesen, RH and Larsen, EB and Rubak, T and Baunwall, SMD and Paaske, SE and Gregersen, M and Foss, CH and Erikstrup, C and Krogh, CB and Ehlers, LH and Hvas, CL}, title = {Cost-Effectiveness of Hospital-at-Home and Fecal Microbiota Transplantation in Treating Older Patients With Clostridioides difficile.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf104}, pmid = {40243343}, issn = {1537-6591}, support = {NNF22OC0074080//Novo Nordisk Foundation/ ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) primarily affects older patients with comorbid conditions and has a high mortality rate. Fecal microbiota transplantation (FMT) is effective and cost-effective for CDI. In a recent study, we demonstrated the clinical benefits of combining hospital-at-home care with FMT for older patients with CDI, but its cost-effectiveness remains unknown. The current study aimed to evaluate the cost-effectiveness of the intervention in patients aged ≥70 years with CDI, compared with standard treatment.<br><br>METHODS: The cost-utility analysis was conducted using data from a randomized clinical trial enrolling 217 patients, assessing the cost-effectiveness of the intervention over 90 days. Resource use was assessed from a healthcare sector perspective. Missing data were handled with proxy replacement and multiple imputation. Sensitivity analyses included probabilistic analysis, complete case analysis, adjustment of key unit prices, and a hospital perspective. A willingness-to-pay threshold was set to &#x20ac;22 994 or $24 863 per quality-adjusted life year (QALY).<br><br>RESULTS: In the base case analysis, the intervention was dominant, with mean cost savings of &#x20ac;2556 ($2764) and a mean gain of 0.004 QALY. Although resource use was higher, the intervention resulted in an average reduction of 6 hospital admission days per patient and increased odds of clinical resolution. The results remained robust across different perspectives, the exclusion of patients with missing data, and variations in hospital admission costs.<br><br>CONCLUSIONS: In patients aged &#x2265;70 years with CDI, an intervention combining hospital-at-home care and FMT is cost-effective compared with standard treatment. The cost-effectiveness is mainly driven by fewer hospital admission days.}, }
@article {pmid40237231, year = {2025}, author = {Saeedi, N and Pourabdolhossein, F and Dadashi, M and Suha, AJ and Janahmadi, M and Behzadi, G and Hosseinmardi, N}, title = {Faecal Microbiota Transplantation Modulates Morphine Addictive-Like Behaviours Through Hippocampal Metaplasticity.}, journal = {Addiction biology}, volume = {30}, number = {4}, pages = {e70034}, pmid = {40237231}, issn = {1369-1600}, support = {//Vice President of Research and Technology of Shahid Beheshti University of Medical Sciences/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Male ; Rats, Wistar ; Rats ; *Morphine/pharmacology ; *Morphine Dependence/therapy/physiopathology ; *Neuronal Plasticity/drug effects/physiology ; *Hippocampus/drug effects/physiopathology ; Substance Withdrawal Syndrome ; Naloxone/pharmacology ; Gastrointestinal Microbiome ; Narcotic Antagonists/pharmacology ; Analgesics, Opioid/pharmacology ; }, abstract = {The microbiota-gut-brain axis has been implicated in the pathology of substance use disorders (SUDs). In light of the brain's capability to reorganize itself in response to intrinsic and extrinsic stimuli, opioid-induced dysbiosis is likely to contribute to addictive behaviour through modulating neuroplasticity. In this study, a faecal microbiota transplantation (FMT) from a saline-donor was performed on morphine-treated rats to evaluate the effects of gut microbiota on morphine-induced metaplasticity and addictive behaviours. Male Wistar rats were treated with subcutaneous injections of 10 mg/kg morphine sulphate every 12 h for 9 days in an effort to induce dependence. The withdrawal syndrome was precipitated by injecting naloxone (1.5 mg/kg, ip) after the final dose of morphine. The tolerance was induced by repeated morphine injections over a period of 7 days (10 mg/kg, once a day, ip). FMT was applied daily through gavage of processed faeces 1 week before and during the morphine treatment. Field potential recordings (i.e., fEPSP) were carried out to assess short-term and long-term synaptic plasticity in the CA1 area of the hippocampus following Schaffer-collateral stimulation. Animals subjected to FMT exhibited significant reductions in naloxone-precipitated withdrawal syndrome (one-way ANOVA, p < 0.05). Tolerance to the analgesic effects of morphine was not affected by FMT (two-way ANOVA, p > 0.05). Following high-frequency stimulation (HFS) to induce long-term potentiation (LTP), a greater fEPSP slope was observed in morphine-treated animals (unpaired t test, p < 0.05). FMT from saline-donor rats diminished morphine-induced augmented LTP (unpaired t test, p < 0.05). These results highlighted the alleviating effects of FMT from saline-donors on morphine-induced metaplasticity and dependence potentially by modulating the dysbiosis of gut microbiota.}, }
@article {pmid40237060, year = {2025}, author = {Li, H and Lai, H and Xing, Y and Zou, S and Yang, X}, title = {Microbiota-gut-brain axis: Novel Potential Pathways for Developing Antiepileptogenic Drugs.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/1570159X23666250414094040}, pmid = {40237060}, issn = {1875-6190}, abstract = {The treatment of epilepsy remains imperfect due to a lack of understanding of its pathogenesis. Although antiseizure medications can control most seizures, up to 30% of patients experience uncontrolled seizures, leading to refractory epilepsy. Therefore, elucidating the pathogenesis of epilepsy and exploring new avenues to design antiepileptic drugs may improve epilepsy treatment. Recent studies have identified an imbalance of the gut microbiota (GM) in both patients with epilepsy and various animal models of epilepsy. In response to this phenomenon, an increasing number of studies have focused on controlling seizures by regulating GM homeostasis, utilizing methods such as dietary restrictions, fecal microbiota transplantation, and the use of prebiotics. Surprisingly, these interventions have shown promising antiepileptic effects, suggesting that GM, through the regulatory role of the microbiota-gut-brain axis (gut-brain axis), may emerge as a novel strategy for treating epilepsy. This review aims to discuss the research progress on the relationship between GM and epilepsy, incorporating the latest clinical studies and animal experiments. We will specifically concentrate on the potential key role of the gut-brain axis in epileptogenesis, epilepsy development, and outcomes of epilepsy. Through a detailed analysis of the underlying mechanisms of the gut-brain axis, we aim to provide a more comprehensive perspective on understanding the pathophysiology of epilepsy and lay the groundwork for the development of new antiepileptic drugs in the future.}, }
@article {pmid40235083, year = {2025}, author = {Brown, R and Barko, P and Ruiz Romero, JDJ and Williams, DA and Gochenauer, A and Nguyen-Edquilang, J and Suchodolski, JS and Pilla, R and Ganz, H and Lopez-Villalobos, N and Gal, A}, title = {The effect of lyophilised oral faecal microbial transplantation on functional outcomes in dogs with diabetes mellitus.}, journal = {The Journal of small animal practice}, volume = {}, number = {}, pages = {}, doi = {10.1111/jsap.13865}, pmid = {40235083}, issn = {1748-5827}, support = {//University of Illinois at Urbana-Champaign Companion Animal Research Grant Program/ ; }, abstract = {OBJECTIVES: We aimed to determine if oral faecal microbiota transplantation improves indices of glycaemic control, changes the faecal dysbiosis indices, alters faecal short-chain fatty acid and bile acid profiles and increases serum glucagon-like-peptide 1 concentrations in diabetic dogs.<br><br>MATERIALS AND METHODS: In this prospective randomised, placebo-controlled, double-blinded pilot study, we recruited nine diabetic dogs (five faecal microbiota transplantation and four placebo) and nine healthy controls.<br><br>RESULTS: Compared to healthy dogs, diabetic dogs had altered faecal short-chain fatty acid and bile acid profiles. In the first 30&#x2009;days, the faecal microbiota transplantation group had a more rapid decline in interstitial glucose; however, the mean interstitial glucose of the faecal microbiota transplantation recipients did not differ from the placebo recipients at the end of the study. Compared with placebo, faecal microbiota transplantation recipients had a decreased 24-hour water intake at day 60 and increased faecal abundance of Faecalibacterium.<br><br>CLINICAL SIGNIFICANCE: This study provides a proof of concept for faecal microbiota transplantation in canine diabetes, and its data could inform the design of future large-scale studies. Further investigation is required to determine whether faecal microbiota transplantation would have any role as an adjunctive therapy in canine diabetes and to elucidate the mechanisms by which faecal microbiota transplantation may provide a beneficial clinical effect in canine diabetes.}, }
@article {pmid40235010, year = {2025}, author = {Chen, M and Pan, J and Song, Y and Liu, S and Sun, P and Zheng, X}, title = {Effect of inulin supplementation in maternal fecal microbiota transplantation on the early growth of chicks.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {98}, pmid = {40235010}, issn = {2049-2618}, support = {20170204043NY2//key technology research. project of Changchun Key R&amp;D Program, and the Outstanding Talents in Science and Technology Innovation/ ; 32472995//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Inulin/administration &amp; dosage/pharmacology ; *Chickens/growth &amp; development/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/drug effects ; Female ; Dietary Supplements ; Feces/microbiology ; Prebiotics/administration &amp; dosage ; }, abstract = {BACKGROUND: Fecal microbial transplantation (FMT) is an important technology for treating diarrhea and enteritis. Additionally, FMT has been applied to improve productivity, alter abnormal behavior, relieve stress, and reduce burdens. However, some previous studies have reported that FMT may cause stress in acceptor animals. Inulin, a prebiotic, can promote growth, enhance immunity, and balance the gut microbiota. Currently, there are limited reports on the effects of combining FMT with inulin on early growth performance in chicks.<br><br>RESULTS: In this study, a total of 90 1-day-old chicks were randomly divided into the control group&#xa0;(CON), FMT&#xa0;group, and inulin group&#xa0;(INU). The CON group was fed a basic diet, whereas the FMT and INU groups received fecal microbiota transplantation and FMT with inulin treatment, respectively. Compared with the FMT and CON groups, the INU group presented significantly greater average daily gain (ADG) and average daily feed intake (ADFI) values (P&#x2009;<&#x2009;0.05). However, the organ indices did not significantly change (P&#x2009;>&#x2009;0.05). The ratio of the villi to crypts in the ileum significantly differed at 21 and 35&#xa0;days (P&#x2009;<&#x2009;0.05). In addition, the cecum concentrations of acetic acid and butyric acid significantly increased in the INU group (P&#x2009;<&#x2009;0.05). In addition, gut inflammation and serum inflammation decreased in the INU group, and immune factors increased after inulin supplementation. (P&#x2009;<&#x2009;0.05). Firmicutes and Bacteroidetes were the dominant phyla, with more than 90% of all sequences being identified as originating from these two phyla. Inulin supplementation during mother-sourced microbial transplantation significantly increased the abundance of Rikenella, Butyricicoccus, and [Ruminococcus], which contributed positively to the promotion of early intestinal health and facilitated the early growth of chicks.<br><br>CONCLUSION: The results of this study suggest that inulin supplementation in maternal fecal microbiota transplantation can effectively promote early growth and probiotic colonization, which favors the health of chicks. Video Abstract.}, }
@article {pmid40234859, year = {2025}, author = {Senthilkumar, H and Arumugam, M}, title = {Gut microbiota: a hidden player in polycystic ovary syndrome.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {443}, pmid = {40234859}, issn = {1479-5876}, mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/physiopathology/therapy ; *Gastrointestinal Microbiome ; Female ; Animals ; Dysbiosis ; }, abstract = {Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects reproductive-aged women worldwide, causing hormonal imbalances and ovarian dysfunction. PCOS affects metabolic health and increases the risk of obesity, insulin resistance, and cardiovascular disease, in addition to infertility. This review delves deeper into the connections of gut microbiota with PCOS pathophysiology, particularly into its impact on hormone metabolism, obesity, inflammation, and insulin resistance by way of short-chain fatty acids, lipopolysaccharides, and gut-brain axis. Studies also show that changes in the metabolic processes and immune responses are seen in changes in the gut microbiota in PCOS subjects, such as changes in the Bacteroidetes and Firmicutes groups. Some bacteria, like Escherichia and Shigella, have been associated with dysbiosis in patients with PCOS, leading to systemic inflammation and changed hormone levels, which further worsen the clinical symptoms. Therapeutic interventions targeting the gut microbiota comprise probiotics, prebiotics, and fecal microbiota transplantation; these have potential to alleviate the symptoms of PCOS. Other precision microbiome-based therapies include postbiotics, and CRISPR-Cas9 genome editing, which are relatively new avenues toward precision treatment. This complex interlink of gut microbiota and PCOS pathophysiology will open the avenues for possible treatments for hormonal imbalances and metabolic problems that characterize these complex disorders. The review here focuses on the requirement of further studies to be able to elucidate the specific pathways relating gut microbiota dysregulation to PCOS and, thus, improve microbiome-based therapies for better clinical outcomes in affected individuals.}, }
@article {pmid40234406, year = {2025}, author = {Sui, Y and Zhang, T and Ou, S and Li, G and Liu, L and Lu, T and Zhang, C and Cao, Y and Bai, R and Zhou, H and Zhao, X and Yuan, Y and Wang, G and Chen, H and Kong, R and Sun, B and Li, L}, title = {Statin therapy associated Lactobacillus intestinalis attenuates pancreatic fibrosis through remodeling intestinal homeostasis.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {59}, pmid = {40234406}, issn = {2055-5008}, support = {82270665//National Natural Science Foundation of China/ ; 82270666//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Homeostasis/drug effects ; Fibrosis ; Fecal Microbiota Transplantation ; Male ; *Pancreas/pathology/drug effects ; Macrophages/immunology ; Mice, Inbred C57BL ; CD8-Positive T-Lymphocytes/immunology ; *Intestines/microbiology/drug effects ; *Lactobacillus ; Disease Models, Animal ; *Probiotics/administration &amp; dosage ; }, abstract = {Chronic pancreatitis (CP) is characterized by irreversible fibrotic destruction and impaired pancreatic function. CP disrupts lipid metabolism and causes the imbalance of gut microbiota which in turn exacerbates pancreatic fibrosis. Statins alter gut microbiota and exert anti-inflammatory effects, but its role in CP has not been fully elucidated. Here, we found that statins-associated higher abundance of Lactobacillus intestinalis (L.intestinalis) maintained gut homeostasis that restrained bacteria translocation from gut to the pancreas, which eventually aggravated pancreatic fibrosis through inhibiting CD8[+]T cells-dependent immunity. Fecal microbiota transplantation (FMT) or L.intestinalis administration inhibited the infiltration of CD8[+]T cells and macrophages that delayed CP progression. L.intestinalis restrained the recruitment of M1 macrophages and limited the release of Ccl2/7 in the colon, which prevented epithelial damage and epithelial barrier dysfunction through blocking Ccl2/7-Ccr1 signaling. Our findings elucidate that the utilization of statin therapy or supplementation of L.intestinalis can be potential approach for the therapies of CP.}, }
@article {pmid40233040, year = {2025}, author = {Pomej, K and Frick, A and Scheiner, B and Balcar, L and Pajancic, L and Klotz, A and Kreuter, A and Lampichler, K and Regnat, K and Zinober, K and Trauner, M and Tamandl, D and Gasche, C and Pinter, M}, title = {Study protocol: Fecal Microbiota Transplant combined with Atezolizumab/Bevacizumab in Patients with Hepatocellular Carcinoma who failed to achieve or maintain objective response to Atezolizumab/Bevacizumab - the FAB-HCC pilot study.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0321189}, pmid = {40233040}, issn = {1932-6203}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Bevacizumab/therapeutic use/administration &amp; dosage ; *Carcinoma, Hepatocellular/therapy/drug therapy ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; *Liver Neoplasms/therapy/drug therapy ; Pilot Projects ; Clinical Trials, Phase II as Topic ; }, abstract = {BACKGROUND: The gut microbiota is often altered in chronic liver diseases and hepatocellular carcinoma (HCC), and increasing evidence suggests that it may influence response to cancer immunotherapy. Strategies to modulate the gut microbiome (i.e., fecal microbiota transplant (FMT)) may help to improve efficacy of immune checkpoint inhibitors (ICIs) or even overcome resistance to ICIs. Here, we describe the design and rationale of FAB-HCC, a single-center, single-arm, phase II pilot study to assess safety, feasibility, and efficacy of FMT from patients with HCC who responded to PD-(L)1-based immunotherapy or from healthy donors to patients with HCC who failed to achieve or maintain a response to atezolizumab plus bevacizumab.<br><br>METHODS: In this single-center, single-arm, phase II pilot study (ClinicalTrials.gov identifier: NCT05750030), we plan to include 12 patients with advanced HCC who failed to achieve or maintain a response to atezolizumab/bevacizumab. Patients will receive a single FMT via colonoscopy from donors with HCC who responded to PD-(L)1-based immunotherapy or from healthy individuals, followed by atezolizumab/bevacizumab every 3 weeks. The primary endpoint is safety, measured by incidence and severity of treatment-related adverse events. The main secondary endpoint is efficacy, as assessed by best radiological response according to RECISTv1.1 and mRECIST. Additional exploratory endpoints include data on the effect of FMT on recipient gut microbiota, as well as metagenomic analysis of stool samples, analyses of circulating immune cells and serum and stool proteomic, metabolomic and lipidomic signatures.<br><br>DISCUSSION: The results of this study will help to define the potential of FMT as add-on intervention in the systemic treatment of advanced HCC, with the potential to improve efficacy of immunotherapy or even overcome resistance.<br><br>TRIAL REGISTRATION: EudraCT Number: 2022-000234-42 Clinical trial registry &amp; ID: ClinicalTrials.gov identifier: NCT05750030 (Registration date: 16.01.2023).}, }
@article {pmid40232107, year = {2025}, author = {Ravizza, T and Volpedo, G and Riva, A and Striano, P and Vezzani, A}, title = {Intestinal microbiome alterations in pediatric epilepsy: Implications for seizures and therapeutic approaches.}, journal = {Epilepsia open}, volume = {}, number = {}, pages = {}, doi = {10.1002/epi4.70037}, pmid = {40232107}, issn = {2470-9239}, support = {PE0000006/DN.1553//National Recovery and Resilience Plan (NRRP)/ ; //AICE-FIRE/ ; }, abstract = {The intestinal microbiome plays a pivotal role in maintaining host health through its involvement in gastrointestinal, immune, and central nervous system (CNS) functions. Recent evidence underscores the bidirectional communication between the microbiota, the gut, and the brain and the impact of this axis on neurological diseases, including epilepsy. In pediatric patients, alterations in gut microbiota composition-called intestinal dysbiosis-have been linked to seizure susceptibility. Preclinical models revealed that gut dysbiosis may exacerbate seizures, while microbiome-targeted therapies, including fecal microbiota transplantation, pre/pro-biotics, and ketogenic diets, show promise in reducing seizures. Focusing on clinical and preclinical studies, this review examines the role of the gut microbiota in pediatric epilepsy with the aim of exploring its implications for seizure control and management of epilepsy. We also discuss mechanisms that may underlie mutual gut-brain communication and emerging therapeutic strategies targeting the gut microbiome as a novel approach to improve outcomes in pediatric epilepsy. PLAIN LANGUAGE SUMMARY: Reciprocal communication between the brain and the gut appears to be dysfunctional in pediatric epilepsy. The composition of bacteria in the intestine -known as microbiota- and the gastrointestinal functions are altered in children with drug-resistant epilepsy and animal models of pediatric epilepsies. Microbiota-targeted interventions, such as ketogenic diets, pre-/post-biotics administration, and fecal microbiota transplantation, improve both gastrointestinal dysfunctions and seizures in pediatric epilepsy. These findings suggest that the gut and its microbiota represent potential therapeutic targets for reducing drug-resistant seizures in pediatric epilepsy.}, }
@article {pmid40231893, year = {2025}, author = {Vargas-Castellanos, E and Rincón-Riveros, A}, title = {Microsatellite Instability in the Tumor Microenvironment: The Role of Inflammation and the Microbiome.}, journal = {Cancer medicine}, volume = {14}, number = {8}, pages = {e70603}, pmid = {40231893}, issn = {2045-7634}, support = {C-012-2023//Hospital Universitario Mayor M&#xe9;deri/ ; }, mesh = {Humans ; *Tumor Microenvironment/immunology/genetics ; *Microsatellite Instability ; *Neoplasms/genetics/microbiology/immunology/pathology ; *Inflammation/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Animals ; Dysbiosis ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {BACKGROUND: Microsatellite instability (MSI) is a hallmark of DNA mismatch repair (MMR) deficiency that leads to genomic instability and increased cancer risk. The tumor microenvironment (TME) significantly influences MSI-driven tumorigenesis, and emerging evidence points to a critical role of the microbiome in shaping this complex interplay.<br><br>METHODS: This review comprehensively examines the existing literature on the intricate relationship between MSI, microbiome, and cancer development, with a particular focus on the impact of microbial dysbiosis on the TME.<br><br>RESULTS: MSI-high tumors exhibited increased immune cell infiltration owing to the generation of neoantigens. However, immune evasion mechanisms such as PD-1/CTLA-4 upregulation limit the efficacy of immune checkpoint inhibitors (ICIs) in a subset of patients. Pathobionts, such as Fusobacterium nucleatum and Bacteroides fragilis, contribute to MSI through the production of genotoxins, further promoting inflammation and oxidative stress within the TME.<br><br>CONCLUSIONS: The microbiome profoundly affects MSI-driven tumorigenesis. Modulation of the gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and dietary changes holds promise for improving ICI response rates. Further research into cancer pharmacomicrobiomics, investigating the interplay between microbial metabolites and anticancer therapies, is crucial for developing personalized treatment strategies.}, }
@article {pmid40230225, year = {2025}, author = {Fang, X and Zhang, Y and Huang, X and Miao, R and Zhang, Y and Tian, J}, title = {Gut microbiome research: Revealing the pathological mechanisms and treatment strategies of type 2 diabetes.}, journal = {Diabetes, obesity &amp; metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1111/dom.16387}, pmid = {40230225}, issn = {1463-1326}, support = {CI2021A01601//Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences/ ; HLCMHPP20230CZ40907//High Level Chinese Medical Hospital Promotion Project/ ; ZZ13-YQ-026//CACMS Outstanding Young Scientific and Technological Talents Program/ ; CI2021B008//Innovation Team Project of Science and Technology Innovation Engineering of China Academy of Chinese Medical Sciences/ ; 82474323//National Natural Science Foundation of China/ ; }, abstract = {The high prevalence and disability rate of type 2 diabetes (T2D) caused a huge social burden to the world. Currently, new mechanisms and therapeutic approaches that may affect this disease are being sought. With in-depth research on the pathogenesis of T2D and growing advances in microbiome sequencing technology, the association between T2D and gut microbiota has been confirmed. The gut microbiota participates in the regulation of inflammation, intestinal permeability, short-chain fatty acid metabolism, branched-chain amino acid metabolism and bile acid metabolism, thereby affecting host glucose and lipid metabolism. Interventions focusing on the gut microbiota are gaining traction as a promising approach to T2D management. For example, dietary intervention, prebiotics and probiotics, faecal microbiota transplant and phage therapy. Meticulous experimental design and choice of analytical methods are crucial for obtaining accurate and meaningful results from microbiome studies. How to design gut microbiome research in T2D and choose different machine learning methods for data analysis are extremely critical to achieve personalized precision medicine.}, }
@article {pmid40229514, year = {2025}, author = {Du, J and Guan, Y and Zhang, E}, title = {Regulatory role of gut microbiota in immunotherapy of hepatocellular carcinoma.}, journal = {Hepatology international}, volume = {}, number = {}, pages = {}, pmid = {40229514}, issn = {1936-0541}, abstract = {BACKGROUND: The gut microbiota plays a role in triggering innate immunity and regulating the immune microenvironment (IME) of hepatocellular carcinoma (HCC) by acting on various signaling receptors and transcription factors through its metabolites and related molecules. Furthermore, there is an increasing recognition of the gut microbiota as a potential therapeutic target for HCC, given its ability to modulate the efficacy of immune checkpoint inhibitors (ICIs).<br><br>OBJECTIVE: This review will discuss the mechanisms of gut microbiota in modulating immunotherapy of HCC, the predictive value of efficacy, and the therapeutic strategies for modulating the gut microbiota in detail.<br><br>METHODS: We conducted a systematic literature search in PubMed, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Chinese databases for articles involving the influence of gut microbiota on HCC immunotherapy.<br><br>RESULTS: The mechanisms underlying the effect of gut microbiota on HCC immunotherapy include gut-liver axis, tumor immune microenvironment (TIME), and antibodies. Patients who benefit from ICIs exhibit a higher abundance of gut microbiota. Antibiotics, fecal microbiota transplantation (FMT), probiotics, and prebiotics are effective methods to regulate gut microbiota.<br><br>CONCLUSION: The strong connection between the liver and gut will provide numerous opportunities for the development of microbiome-based diagnostics, treatments, or prevention strategies for HCC patients.}, }
@article {pmid40229213, year = {2025}, author = {Hoops, SL and Moutsoglou, D and Vaughn, BP and Khoruts, A and Knights, D}, title = {Metagenomic source tracking after microbiota transplant therapy.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2487840}, pmid = {40229213}, issn = {1949-0984}, mesh = {Humans ; *Metagenomics/methods ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Colitis, Ulcerative/therapy/microbiology ; *Bacteria/genetics/classification/isolation &amp; purification ; RNA, Ribosomal, 16S/genetics ; *Metagenome ; Bayes Theorem ; Feces/microbiology ; }, abstract = {Reliable engraftment assessment of donor microbial communities and individual strains is an essential component of characterizing the pharmacokinetics of microbiota transplant therapies (MTTs). Recent methods for measuring donor engraftment use whole-genome sequencing and reference databases or metagenome-assembled genomes (MAGs) to track individual bacterial strains but lack the ability to disambiguate DNA that matches both donor and patient microbiota. Here, we describe a new, cost-efficient analytic pipeline, MAGEnTa, which compares post-MTT samples to a database comprised MAGs derived directly from donor and pre-treatment metagenomic data, without relying on an external database. The pipeline uses Bayesian statistics to determine the likely sources of ambiguous reads that align with both the donor and pre-treatment samples. MAGEnTa recovers engrafted strains with minimal type II error in a simulated dataset and is robust to shallow sequencing depths in a downsampled dataset. Applying MAGEnTa to a dataset from a recent MTT clinical trial for ulcerative colitis, we found the results to be consistent with 16S rRNA gene SourceTracker analysis but with added MAG-level specificity. MAGEnTa is a powerful tool to study community and strain engraftment dynamics in the development of MTT-based treatments that can be integrated into frameworks for functional and taxonomic analysis.}, }
@article {pmid40227949, year = {2025}, author = {He, Y and Cai, J and Xie, X and Zhang, X and Qu, L and Liu, J and Cao, Y}, title = {Dimethyl Itaconate Alleviates Escherichia coli-Induced Endometritis Through the Guanosine-CXCL14 Axis via Increasing the Abundance of norank_f_Muribaculaceae.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2414792}, doi = {10.1002/advs.202414792}, pmid = {40227949}, issn = {2198-3844}, support = {2023YFD1801100//Key Technologies Research and Development Program of Anhui Province/ ; }, abstract = {Endometritis, a prevalent reproductive system disease with high incidence, leads to reproductive dysfunction in humans and animals, causing huge economic losses. Dimethyl itaconate (DI) has been demonstrated to exert protective effects in multiple inflammatory diseases. Nevertheless, the efficacy of DI in preventing endometritis and the role played by the gut microbiota remain unknown. In this study, it is found that DI ameliorated Escherichia coli (E. coli) induced endometritis in mice. The protective effect is abolished by antibiotic-induced depletion of the gut microbiota, and fecal microbiota transplantation (FMT) from DI-treated mice to recipient mice ameliorated E. coli-induced endometritis. Integrative multiomics reveals that DI promotes the multiplication of norank_f_Muribaculaceae in vivo, and supplementation of Muribaculum intestinale (DSM 28989), which belongs to the norank_f_Muribaculaceae genus, upregulates the level of guanosine in the uterus. Mechanistically, the protective effect of guanosine in endometritis is mediated by activating the expression of CXCL14 in uterine epithelial cells. Moreover, the antibody-neutralizing experiment of CXCL14 eliminated this protective effect. In conclusion, this study elucidates the significant role of the gut microbiota and its metabolites in the protection of DI against endometritis, and provides new evidence for the regulation of distal organ by the gut microbiota.}, }
@article {pmid40223320, year = {2025}, author = {Yaghmaei, H and Taromiha, A and Nojoumi, SA and Soltanipur, M and Shahshenas, S and Rezaei, M and Mirhosseini, SM and Hosseini, SM and Siadat, SD}, title = {Role of Gut-Liver Axis in Non-Alcoholic Fatty Liver Disease.}, journal = {Iranian biomedical journal}, volume = {29}, number = {1 &amp; 2}, pages = {1-8}, pmid = {40223320}, issn = {2008-823X}, mesh = {*Non-alcoholic Fatty Liver Disease/microbiology ; Humans ; *Gastrointestinal Microbiome ; Animals ; *Liver/pathology/microbiology/metabolism ; Dysbiosis ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant global health problem, mainly due to the increasing prevalence of obesity and metabolic syndrome. The gut microbiota plays an essential role in the development of NAFLD through the gut-liver axis. Dysbiosis of. the gut microbiota (GM) is associated with the pathogenesis of NAFLD. Dietary choices and other lifestyle factors influence the composition of the GM and contribute to the development of NAFLD. At the phylum level, individuals with NAFLD show an increased level in Actinobacteria and Firmicutes, while Verrucomicrobia, Thermus, Proteobacteria, Lentiphaerae, and Fusobacteria are found to be decreased. Several genera, including Faecalibacterium and Akkermansia, exhibit alterations in NAFLD and are linked to disease progression. Modulating the GM through prebiotics, probiotics, or fecal microbiota transplantation represents a promising therapeutic strategy for NAFLD. This review summarizes the current understanding of GM changes in NAFLD, focusing on findings from both human and animal studies.}, }
@article {pmid40221450, year = {2025}, author = {Kim, KS and Noh, J and Kim, BS and Koh, H and Lee, DW}, title = {Refining microbiome diversity analysis by concatenating and integrating dual 16S rRNA amplicon reads.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {57}, pmid = {40221450}, issn = {2055-5008}, support = {RS-2021-NR056579//National Research Foundation of Korea (NRF)/ ; RS-2023-KH141436//Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs)/ ; 200118770//Ministry of Trade, Industry and Energy (Ministry of Trade, Industry and Energy, Korea)/ ; }, mesh = {*RNA, Ribosomal, 16S/genetics ; Humans ; *Gastrointestinal Microbiome/genetics ; *Bacteria/classification/genetics/isolation &amp; purification ; *Metagenomics/methods ; Sequence Analysis, DNA/methods ; Metagenome ; Colitis, Ulcerative/microbiology ; DNA, Bacterial/genetics ; Republic of Korea ; Phylogeny ; Feces/microbiology ; Biodiversity ; High-Throughput Nucleotide Sequencing ; }, abstract = {Understanding the role of human gut microbiota in health and disease requires insights into its taxonomic composition and functional capabilities. This study evaluates whether concatenating paired-end reads enhances data output for gut microbiome analysis compared to the merging approach across various regions of the 16S rRNA gene. We assessed this approach in both mock communities and Korean cohorts with or without ulcerative colitis. Our results indicate that using the direct joining method for the V1-V3 or V6-V8 regions improves taxonomic resolution compared to merging paired-end reads (ME) in post-sequencing data. While predicting microbial function based on 16S rRNA sequencing has inherent limitations, integrating sequencing reads from both the V1-V3 and V6-V8 regions enhanced functional predictions. This was confirmed by whole metagenome sequencing (WMS) of Korean cohorts, where our approach improved taxa detection that was lost using the ME method. Thus, we propose that the integrated dual 16S rRNA sequencing technique serves as a valuable tool for microbiome research by bridging the gap between amplicon sequencing and WMS.}, }
@article {pmid40220715, year = {2025}, author = {Chen, Y and Chen, Z and Liang, L and Li, J and Meng, L and Yuan, W and Xie, B and Zhang, X and Feng, L and Jia, Y and Fu, Z and Su, P and Tong, Z and Zhong, J and Liu, X}, title = {Multi-kingdom gut microbiota dysbiosis is associated with the development of pulmonary arterial hypertension.}, journal = {EBioMedicine}, volume = {115}, number = {}, pages = {105686}, pmid = {40220715}, issn = {2352-3964}, abstract = {BACKGROUND: Gut microbiota dysbiosis has been implicated in pulmonary arterial hypertension (PAH). However, the exact roles and underlying mechanisms of multi-kingdom gut microbiota, including bacteria, archaea, and fungi, in PAH remain largely unclear.<br><br>METHODS: The shotgun metagenomics was used to analyse multi-kingdom gut microbial communities in patients with idiopathic PAH (IPAH) and healthy controls. Furthermore, fecal microbiota transplantation (FMT) was performed to transfer gut microbiota from IPAH patients or monocrotaline (MCT)-PAH rats to normal rats and from normal rats to MCT-PAH rats.<br><br>FINDINGS: Gut microbiota analysis revealed substantial alterations in the bacterial, archaeal, and fungal communities in patients with IPAH compared with healthy controls. Notably, FMT from IPAH patients or MCT-PAH rats induced PAH phenotypes in recipient rats. More intriguingly, FMT from normal rats to MCT-PAH rats significantly ameliorated PAH symptoms; restored gut bacteria, archaea, and fungi composition; and shifted the plasma metabolite profiles of MCT-PAH rats toward those of normal rats. In parallel, RNA-sequencing analysis demonstrated the expression of genes involved in key signalling pathways related to PAH. A panel of multi-kingdom markers exhibited superior diagnostic accuracy compared with single-kingdom panels for IPAH.<br><br>INTERPRETATION: Our findings established an association between multi-kingdom gut microbiota dysbiosis and PAH, thereby indicating the therapeutic potential of FMT in PAH. More importantly, apart from gut bacteria, gut archaea and fungi were also significantly associated with PAH pathogenesis, highlighting their indispensable role in PAH.<br><br>FUNDING: This work was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Projects No. 2024ZD0531200, No. 2024ZD0531201 (Research on Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases, and Metabolic Diseases), the National Natural Science Foundation of China of China (No. 82170302, 82370432), Financial Budgeting Project of Beijing Institute of Respiratory Medicine (Ysbz2025004, Ysbz2025007), National clinical key speciality construction project Cardiovascular Surgery, Reform and Development Program of Beijing Institute of Respiratory Medicine (Ggyfz202417, Ggyfz202501), Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (CYFH202209).}, }
@article {pmid40220396, year = {2025}, author = {Kou, G and Yao, S and Ullah, A and Fang, S and Guo, E and Bo, Y}, title = {Polystyrene microplastics impair brown and beige adipocyte function via the gut microbiota-adipose tissue crosstalk in high-fat diet mice.}, journal = {Journal of hazardous materials}, volume = {492}, number = {}, pages = {138225}, doi = {10.1016/j.jhazmat.2025.138225}, pmid = {40220396}, issn = {1873-3336}, abstract = {BACKGROUND: Microplastics (MPs) are pervasive in the environment and food. The potential health hazards of this emerging pollutant have raised significant concerns in recent years. However, the underlying mechanism by which MPs have any impact on brown and beige adipocytes in the context of obesity is yet to be investigated.<br><br>METHODS: The C57BL/6&#x202f;J mice were randomly assigned to the HFD and HFD+MPs group for 12 weeks of exposure to explore the differences in brown and beige adipocyte function. The gut microbiota analysis, fecal microbiota transplantation and metabolomic profiling were carried out to further determine its potential mechanism.<br><br>RESULTS: The present work demonstrated that high-fat diet mice accumulate lipids and have reduced energy expenditure after three months of oral administration of MPs. In addition to escalating intestinal dysbiosis, exposing HFD mice to MPs induces thermogenic dysfunction in inguinal white adipose tissue and brown adipose tissue. Following the fecal microbiota transplantation, the accumulation of lipids and dysfunction in energy expenditure within the microbiota of recipient mice further elucidated the inhibitory effect of MPs.<br><br>CONCLUSIONS: Our results suggest that MPs induced the thermogenic dysfunction of BAT and iWAT by affecting gut microbiota composition. The present study highlights the mechanisms by which MPs produce thermogenic dysfunction in BAT and iWAT and disruption in the gastrointestinal microbiota.}, }
@article {pmid40220293, year = {2025}, author = {Damiani, F and Giuliano, MG and Cornuti, S and Putignano, E and Tognozzi, A and Suckow, V and Kalscheuer, VM and Pizzorusso, T and Tognini, P}, title = {Multi-site investigation of gut microbiota in CDKL5 deficiency disorder mouse models: Targeting dysbiosis to improve neurological outcomes.}, journal = {Cell reports}, volume = {44}, number = {4}, pages = {115546}, pmid = {40220293}, issn = {2211-1247}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Disease Models, Animal ; *Dysbiosis/microbiology ; Mice ; Mice, Knockout ; Microglia/pathology/metabolism ; Fecal Microbiota Transplantation ; *Spasms, Infantile/microbiology ; *Protein Serine-Threonine Kinases/deficiency/genetics ; *Epileptic Syndromes/microbiology ; *Rett Syndrome/microbiology ; Mice, Inbred C57BL ; Male ; Female ; }, abstract = {Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disorder often associated with gastrointestinal (GI) issues and subclinical immune dysregulation, suggesting a link to the gut microbiota. We analyze the fecal microbiota composition in two CDKL5 knockout (KO) mouse models at postnatal days (P) 25, 32 (youth), and 70 (adulthood), revealing significant microbial imbalances, particularly during juvenile stages. To investigate the role of the intestinal microbiota in CDD and assess causality, we administer antibiotics, which lead to improved visual cortical responses and reduce hyperactivity. Additionally, microglia morphology changes, indicative of altered surveillance and activation states, are reversed. Strikingly, fecal transplantation from CDKL5 KO to wild-type (WT) recipient mice successfully transfers both visual response deficits and hyperactive behavior. These findings show that gut microbiota alterations contribute to the severity of neurological symptoms in CDD, shedding light on the interplay between microbiota, microglia, and neurodevelopmental outcomes.}, }
@article {pmid40219707, year = {2025}, author = {Li, M and Bao, Y and Ren, J and Wei, W and Yu, X and He, X and Gulisima, M and Sheng, L and Zheng, N and Wan, J and Zhou, H and Zhao, L and Li, H}, title = {Aged Gut Microbiota Contributes to Cognitive Impairment and Hippocampal Synapse Loss in Mice.}, journal = {Aging cell}, volume = {}, number = {}, pages = {e70064}, doi = {10.1111/acel.70064}, pmid = {40219707}, issn = {1474-9726}, support = {21XD1403500//Shanghai Excellent Academic Leaders Program/ ; //"Youth Qi Huang Scholar" by State Administration of TCM/ ; 2021YFE0111800//2021 UK-China Health and Ageing Flagship Challenge/ ; 81871098//National Natural Science Foundation of China/ ; }, abstract = {Gut microbiota alteration during the aging process serves as a causative factor for aging-related cognitive decline, which is characterized by the early hallmark, hippocampal synaptic loss. However, the impact and mechanistic role of gut microbiota in hippocampal synapse loss during aging remains unclear. Here, we observed that the fecal microbiota of naturally aged mice successfully transferred cognitive impairment and hippocampal synapse loss to young recipients. Multi-omics analysis revealed that aged gut microbiota was characterized with obvious change in Bifidobacterium pseudolongum (B.p) and metabolite of tryptophan, indoleacetic acid (IAA) in the periphery and brain. These features were also reproduced in young recipients that were transplanted with aged gut microbiota. Fecal B.p abundance was reduced in patients with cognitive impairment compared to healthy subjects and showed a positive correlation with cognitive scores. Microbiota transplantation from patients who had fewer B.p abundances yielded worse cognitive behavior in mice than those with higher B.p abundances. Meanwhile, supplementation of B.p was capable of producing IAA and enhancing peripheral and brain IAA bioavailability, as well as improving cognitive behaviors and microglia-mediated synapse loss in 5 × FAD transgenic mice. IAA produced from B.p was shown to prevent microglia engulfment of synapses in an aryl hydrocarbon receptor-dependent manner. This study reveals that aged gut microbiota -induced cognitive decline and microglia-mediated synapse loss that is, at least partially, due to the deficiency in B.p and its metabolite, IAA. It provides a proof-of-concept strategy for preventing neurodegenerative diseases by modulating gut probionts and their tryptophan metabolites.}, }
@article {pmid40219669, year = {2025}, author = {Murray, J and Kefayat, A and Finlayson, M and Seenan, JP and Hsu, R and Din, S}, title = {RCPE in association with the American College of Gastroenterology and the Scottish Society of Gastroenterology - Gastroenterology: A global perspective.}, journal = {The journal of the Royal College of Physicians of Edinburgh}, volume = {}, number = {}, pages = {14782715251332318}, doi = {10.1177/14782715251332318}, pmid = {40219669}, issn = {2042-8189}, abstract = {On 6 November 2024, the Royal College of Physicians of Edinburgh (RCPE) hosted its annual gastroenterology symposium, marking the first collaboration with the American College of Gastroenterology (ACG) and the Scottish Society of Gastroenterology (SSG). The event addressed key global challenges in gastroenterology, including obesity, liver disease, inflammatory bowel disease (IBD), the gut microbiome, endoscopy quality and artificial intelligence (AI) applications. Discussions emphasised the growing burden of metabolic dysfunction-associated steatotic liver disease (MASLD), with promising pharmacologic and endoscopic interventions emerging. Advances in microbiome-targeted therapies, including faecal microbiota transplantation (FMT), were explored for recurrent Clostridium difficile infection and IBD. Professor David Rubin delivered the esteemed Sir Stanley Davidson lecture, highlighting the era of disease modification in IBD, emphasising early intervention and personalised treatment strategies. The symposium also addressed the role of AI in improving endoscopic detection rates and optimising resource allocation. This international collaboration underscored the importance of a multidisciplinary approach to tackling global digestive diseases, integrating clinical innovation, policy interventions and technological advancements. The event fostered knowledge exchange among global experts, aiming to advance patient care and improve long-term outcomes in gastroenterology.}, }
@article {pmid40218893, year = {2025}, author = {Młynarska, E and Barszcz, E and Budny, E and Gajewska, A and Kopeć, K and Wasiak, J and Rysz, J and Franczyk, B}, title = {The Gut-Brain-Microbiota Connection and Its Role in Autism Spectrum Disorders.}, journal = {Nutrients}, volume = {17}, number = {7}, pages = {}, pmid = {40218893}, issn = {2072-6643}, mesh = {Humans ; *Autism Spectrum Disorder/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/complications/microbiology ; *Brain/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *Brain-Gut Axis ; }, abstract = {Autism spectrum disorder (ASD) is a group of complex neurodevelopmental conditions with a heterogeneous and multifactorial etiology that is not yet fully understood. Among the various factors that may contribute to ASD development, alterations in the gut microbiota have been increasingly recognized. Microorganisms in the gastrointestinal tract play a crucial role in the gut-brain axis (GBA), affecting nervous system development and behavior. Dysbiosis, or an imbalance in the microbiota, has been linked to both behavioral and gastrointestinal (GI) symptoms in individuals with ASD. The microbiota interacts with the central nervous system through mechanisms such as the production of short-chain fatty acids (SCFAs), the regulation of neurotransmitters, and immune system modulation. Alterations in its composition, including reduced diversity or an overabundance of specific bacterial taxa, have been associated with the severity of ASD symptoms. Dietary modifications, such as gluten-free or antioxidant-rich diets, have shown potential for improving gut health and alleviating behavioral symptoms. Probiotics, with their anti-inflammatory properties, may support neural health and reduce neuroinflammation. Fecal microbiota transplantation (FMT) is being considered, particularly for individuals with persistent GI symptoms. It has shown promising outcomes in enhancing microbial diversity and mitigating GI and behavioral symptoms. However, its limitations should be considered, as discussed in this narrative review. Further research is essential to better understand the long-term effects and safety of these therapies. Emphasizing the importance of patient stratification and phenotype characterization is crucial for developing personalized treatment strategies that account for individual microbiota profiles, genetic predispositions, and coexisting conditions. This approach could lead to more effective interventions for individuals with ASD. Recent findings suggest that gut microbiota may play a key role in innovative therapeutic approaches to ASD management.}, }
@article {pmid40216789, year = {2025}, author = {Shekarriz, S and Szamosi, JC and Whelan, FJ and Lau, JT and Libertucci, J and Rossi, L and Fontes, ME and Wolfe, M and Lee, CH and Moayyedi, P and Surette, MG}, title = {Detecting microbial engraftment after FMT using placebo sequencing and culture enriched metagenomics to sort signals from noise.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3469}, pmid = {40216789}, issn = {2041-1723}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Metagenomics/methods ; *Colitis, Ulcerative/therapy/microbiology ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; Male ; Female ; Placebos ; Adult ; Middle Aged ; }, abstract = {Fecal microbiota transplantation (FMT) has shown efficacy for the treatment of ulcerative colitis but with variable response between patients and trials. The mechanisms underlying FMT's therapeutic effects remains poorly understood but is generally assumed to involve engraftment of donor microbiota into the recipient's microbiome. Reports of microbial engraftment following FMT have been inconsistent between studies. Here, we investigate microbial engraftment in a previous randomized controlled trial (NCT01545908), in which FMT was sourced from a single donor, using amplicon-based profiling, shotgun metagenomics, and culture-enriched metagenomics. Placebo samples were included to estimate engraftment noise, and a significant level of false-positive engraftment was observed which confounds the prediction of true engraftment. We show that analyzing engraftment across multiple patients from a single donor enhances the accuracy of detection. We identified a unique set of genes engrafted in responders to FMT which supports strain displacement as the primary mechanism of engraftment in our cohort.}, }
@article {pmid40216297, year = {2025}, author = {Tanabe, M and Kunisawa, K and Saito, I and Ojika, H and Saito, K and Nabeshima, T and Mouri, A}, title = {High-Cellulose Diet Ameliorates Cognitive Impairment by Modulating Gut Microbiota and Metabolic Pathways in Mice.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tjnut.2025.04.004}, pmid = {40216297}, issn = {1541-6100}, abstract = {BACKGROUND: Nutrition is a key factor in cognitive function, and safe dietary interventions are promising to prevent cognitive impairment in pediatric psychiatric disorders. We previously demonstrated that childhood social isolation (SI) stress affects colonic function, leading to cognitive impairment. Cellulose, an insoluble dietary fiber, shows benefits to intestinal health, but its potential impact on cognitive impairment has not been explored.<br><br>OBJECTIVES: This study investigated whether a high-cellulose diet ameliorates cognitive impairment induced by SI through modulation of gut microbiota and metabolic pathways.<br><br>METHODS: C57BL/6J male mice (3 wk old; n = 10-15/group) were randomly divided into 2 groups: individually housed (SI) group and housed 5 mice per cage (group-housed) group. Each group received either a normal diet (5% cellulose) or a high-cellulose diet (30% cellulose) for 5 wk daily until the end of the behavioral testing. We evaluated behavior abnormalities, gut microbiota composition, and metabolites, and performed 2-way analysis of variance.<br><br>RESULTS: Intake of a high-cellulose diet ameliorated cognitive impairment, including decreased time spent in a novel location of SI mice in novel object location test (NOLT; +30%; P < 0.01) with reduction of Iba-1 positive cells, microglia, in the hippocampus (-33%; P < 0.05). The high-cellulose diet indicated a significant difference in gut microbiota clustering plots (P < 0.01) and enhanced the variation in malate-aspartate shuttle pathways in SI mice (P < 0.01). Notably, fecal microbiota transplantation (FMT) from SI mice fed a high-cellulose diet after antibiotic treatment, replicated amelioration of cognitive impairment in NOLT (+46%; P < 0.01). Additionally, the FMT replicated a decrease of Iba-1 positive cells indicating suppressed hippocampal microglial activation (-52%; P < 0.01), and enhanced the variation in malate-aspartate shuttle pathways (P < 0.01).<br><br>CONCLUSIONS: These findings suggest that a high-cellulose diet may ameliorate pediatric-specific cognitive impairment through modulation of the gut microbiota and metabolic pathways.}, }
@article {pmid40211390, year = {2025}, author = {Wang, Z and Gao, X and Ji, H and Shao, M and Ni, B and Fei, S and Sun, L and Chen, H and Tan, R and Du, M and Gu, M}, title = {Characterization of gut microbiota and metabolites in renal transplant recipients during COVID-19 and prediction of one-year allograft function.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {420}, pmid = {40211390}, issn = {1479-5876}, support = {82170769//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Kidney Transplantation ; *COVID-19/metabolism/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; Female ; Male ; Middle Aged ; Adult ; *Metabolome ; SARS-CoV-2 ; Allografts ; Transplant Recipients ; Feces/microbiology ; Aged ; }, abstract = {BACKGROUND: The gut-lung-kidney axis is pivotal in immune-related kidney diseases, with gut dysbiosis potentially exacerbating the severity of Coronavirus disease 2019 (COVID-19) in recipients of kidney transplant. This study aimed to characterize the gut microbiome and metabolome in renal transplant recipients with COVID-19 pneumonia over a one-year follow-up period.<br><br>METHODS: A total of 30 renal transplant recipients were enrolled, comprising 17 with COVID-19 pneumonia, six with mild COVID-19, and seven without COVID-19. Fecal samples were collected at the onset of infection for gut microbiome and metabolome analysis. Generalized Estimating Equations (GEE) model and Latent Class Growth Mixed Model (LCGMM) were employed to dissect the relationships among clinical characteristics, laboratory tests, and gut microbiota and metabolites.<br><br>RESULTS: Four microbial phyla (Deferribacteres, TM7, Fusobacteria, and Gemmatimonadetes) and 13 genera were significantly enriched across three recipients groups, correlating with baseline inflammatory response and allograft function. Additionally, 52 differentially expressed metabolites were identified, with seven significantly correlating with eight altered microbiota genera. LCGMM revealed two distinct classes of recipients, with those suffering from COVID-19 pneumonia exhibiting significantly elevated serum creatinine (Scr) trajectories over the one-year period. GEE further identified 12 genera and 181 metabolites closely associated with these trajectories; a multivariable model incorporating gut metabolites of 1-Caffeoylquinic Acid and PMK was found to effectively predict one-year allograft function.<br><br>CONCLUSIONS: Our study indicates a possible interaction between the composition of the gut microbiota and metabolites community and COVID-19 in renal transplant recipients, particularly in relation to disease severity and the prediction of one-year allograft function.}, }
@article {pmid40211191, year = {2025}, author = {Li, A and Costello, SP and Bryant, RV and Haylock-Jacobs, S and Haifer, C and Lee, C and Yeung, D and Giri, P and Blunt, D and Bowen, JB and Ryan, FJ and Yong, A and Wardill, HR}, title = {A study protocol for a double-blinded, randomised, placebo-controlled trial on the use of encapsulated FMT for reducing the side effects of HSCT: the HSCT-BIOME study.}, journal = {BMC cancer}, volume = {25}, number = {1}, pages = {656}, pmid = {40211191}, issn = {1471-2407}, support = {#2021/81-QA25313//Hospital Research Foundation/ ; 2033529//National Health and Medical Research Council/ ; }, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods/adverse effects ; Gastrointestinal Microbiome ; Adult ; Female ; Male ; *Hematologic Neoplasms/therapy ; Randomized Controlled Trials as Topic ; Middle Aged ; Diarrhea/etiology/prevention &amp; control ; Transplantation, Autologous ; Young Adult ; }, abstract = {BACKGROUND: The composition of the gut microbiota both prior to and after haematopoietic stem cell transplantation (HSCT) is increasingly implicated in the outcomes of HSCT, including infections, poor immune reconstitution and disease relapse. Faecal microbiota transplantation (FMT) offers a potential strategy of supporting the gut microbiota and improve HSCT outcomes. Although FMT has been investigated in HSCT recipients, it has largely been evaluated therapeutically for indications such as infection, or once immunocompetency is regained.<br><br>METHODS: Peri-HSCT FMT (i.e. before and after HSCT) will be administered to eligible participants (adults undergoing autologous HSCT for a haematological malignancy) over two courses, with the first delivered immediately prior to conditioning and the second starting when ANC&#x2009;>&#x2009;0.8. Following an open-label, safety run in (N&#x2009;=&#x2009;5), peri-HSCT FMT will be evaluated for its efficacy in 51 participants, randomised 2:1 to FMT or placebo. The primary outcome is the proportion of participants who develop severe gastrointestinal toxicity defined by 3 consecutive days of severe diarrhoea (Bristol Stool Chart 6+), at a frequency of 4&#x2009;+&#x2009;bowel movements/day within 3 weeks of HSCT. Safety is defined as the incidence of treatment-emergent adverse events (TE-AEs). Tolerability is defined as the incidence of TE-AEs and adherence to FMT.<br><br>DISCUSSION: The HSCT-BIOME study is a multi-centre, double-blind, randomised placebo-controlled trial designed to determine the tolerability, safety and efficacy of orally-administered encapsulated FMT to promote the stability of the gastrointestinal microenvironment for HSCT recipients. Peri-HSCT delivered FMT is hypothesised to promote microbial composition both before and following HSCT. Thus, the study will determine if administration of FMT post-HSCT during the neutropenic phase will enhance efficacy.<br><br>TRIAL REGISTRATION: ACTRN12624001104549. Date of registration: September 19, 2024 (prospectively registered).}, }
@article {pmid40210439, year = {2025}, author = {Smith, BJ and Zhao, C and Dubinkina, V and Jin, X and Zahavi, L and Shoer, S and Moltzau-Anderson, J and Segal, E and Pollard, KS}, title = {Accurate estimation of intraspecific microbial gene content variation in metagenomic data with MIDAS v3 and StrainPGC.}, journal = {Genome research}, volume = {35}, number = {5}, pages = {1247-1260}, pmid = {40210439}, issn = {1549-5469}, support = {R01 HL160862/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Metagenomics/methods ; *Gastrointestinal Microbiome/genetics ; *Metagenome ; *Genetic Variation ; *Bacteria/genetics/classification ; }, abstract = {Metagenomics has greatly expanded our understanding of the human gut microbiome by revealing a vast diversity of bacterial species within and across individuals. Even within a single species, different strains can have highly divergent gene content, affecting traits such as antibiotic resistance, metabolism, and virulence. Methods that harness metagenomic data to resolve strain-level differences in functional potential are crucial for understanding the causes and consequences of this intraspecific diversity. The enormous size of pangenome references, strain mixing within samples, and inconsistent sequencing depth present challenges for existing tools that analyze samples one at a time. To address this gap, we updated the MIDAS pangenome profiler, now released as version 3, and developed StrainPGC, an approach to strain-specific gene content estimation that combines strain tracking and correlations across multiple samples. We validate our integrated analysis using a complex synthetic community of strains from the human gut and find that StrainPGC outperforms existing approaches. Analyzing a large, publicly available metagenome collection from inflammatory bowel disease patients and healthy controls, we catalog the functional repertoires of thousands of strains across hundreds of species, capturing extensive diversity missing from reference databases. Finally, we apply StrainPGC to metagenomes from a clinical trial of fecal microbiota transplantation for the treatment of ulcerative colitis. We identify two Escherichia coli strains, from two different donors, that are both frequently transmitted to patients but have notable differences in functional potential. StrainPGC and MIDAS v3 together enable precise, intraspecific pangenomic investigations using large collections of metagenomic data without microbial isolation or de novo assembly.}, }
@article {pmid40210198, year = {2025}, author = {Fu, M and Wang, QW and Liu, YR and Chen, SJ}, title = {The role of the three major intestinal barriers in ulcerative colitis in the elderly.}, journal = {Ageing research reviews}, volume = {108}, number = {}, pages = {102752}, doi = {10.1016/j.arr.2025.102752}, pmid = {40210198}, issn = {1872-9649}, abstract = {With the unprecedented pace of global population aging, there has been a parallel epidemiological shift marked by increasing incidence rates of ulcerative colitis (UC) in geriatric populations, imposing a substantial disease burden on healthcare systems globally. The etiopathogenesis of UC in the elderly remains poorly delineated, while current therapeutic strategies require further optimization to accommodate the unique pathophysiological characteristics of elderly patients. This review systematically elucidates the three barrier dysfunction - encompassing the gut microbiota ecosystem, mucosal epithelial integrity, and immunoregulatory network - that collectively drives UC pathogenesis during biological senescence. We emphasize the therapeutic potential of barrier-targeted interventions, particularly highlighting emerging modalities including fecal microbiota transplantation, intestinal organoid regeneration techniques, mesenchymal stem cell-mediated immunomodulation, and precision-engineered Chimeric Antigen Receptor T-cell therapies. Through this multidimensional analysis, we propose a paradigm-shifting approach to UC management in the elderly, advocating for the development of tailored and evidence-based therapeutic interventions that address the complex interplay between age-related biological changes and intestinal barrier homeostasis in elderly patients.}, }
@article {pmid40210031, year = {2025}, author = {Zhao, M and Liu, Z and Geng, Y and Lv, X and Xu, J and Zhao, X and Yu, Z and Zhu, R and Li, M and Han, F and Ma, X and Gu, N}, title = {Role of a low-molecular-weight polysaccharide from Boletus edulis Bull: Fr. in modulating gut microbiota and metabolic disorders.}, journal = {International journal of biological macromolecules}, volume = {309}, number = {Pt 3}, pages = {142789}, doi = {10.1016/j.ijbiomac.2025.142789}, pmid = {40210031}, issn = {1879-0003}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/pharmacology/chemistry ; Mice ; Male ; *Metabolic Diseases/drug therapy/metabolism/microbiology ; Diet, High-Fat/adverse effects ; Molecular Weight ; Lipid Metabolism/drug effects ; Toll-Like Receptor 4/metabolism ; }, abstract = {This study aimed to investigate the effects of Boletus edulis Bull: Fr. polysaccharide (BEP), extracted using a deep eutectic solvent based on l-lactic acid and glycine, on glucose and lipid metabolism in high-fat diet (HFD)-fed mice. The primary mechanism by which BEP improves symptoms of glucose and lipid imbalances involves the modulation of gut microbiota. Key beneficial bacteria, including S24-7, Lachnospiraceae, [Prevotella], and Lactobacillus, were significantly enriched in the intestines of BEP-treated mice, with abundances 2.48-, 1.62-, 6.33- and 2.60-fold higher, respectively, compared to the HFD group. In contrast, the abundance of harmful bacteria, particularly Desulfovibrio, was reduced by 1.81-fold. These microbial shifts contributed to the alleviation of intestinal mucus layer damage and a 50 % reduction in serum lipopolysaccharide (LPS) levels, a key driver of systemic inflammation, compared to the HFD group. As a result, BEP effectively inhibited LPS-induced activation of the hepatic TLR4/Myd88/MAPK signaling pathway, thereby normalizing the expression of proteins related to glucose and lipid metabolism. A fecal microbiota transplantation study further demonstrated that the gut microbiota changes induced by BEP were central to its anti-metabolic syndrome effects. Overall, BEP may serve as a dietary supplement for preventing and treating diet-induced metabolism disorders by targeting the gut microbiota.}, }
@article {pmid40209695, year = {2025}, author = {Yamane, T and Masaoka, T and Ishii, C and Masuoka, H and Suda, W and Kurokawa, S and Kishimoto, T and Mikami, Y and Fukuda, S and Kanai, T}, title = {Factors contributing to the efficacy of fecal microbiota transplantation for diarrhea-dominant functional bowel disorders.}, journal = {Digestion}, volume = {}, number = {}, pages = {1-22}, doi = {10.1159/000545183}, pmid = {40209695}, issn = {1421-9867}, abstract = {INTRODUCTION: In cases of effective fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), donor feces have been observed to be enriched in Bifidobacterium spp., and FMT for functional bowel disease improved psychiatric symptoms. Although intestinal dysbiosis has received attention as one of the pathophysiologies of IBS, the efficacy of FMT for IBS has not yet been established. In this study, we performed a post-hoc analysis of the efficacy of FMT, focusing on metabolites in donor feces.<br><br>METHODS: FMT was performed in 12 patients, 8 with refractory diarrhea-predominant IBS and 4 with functional diarrhea (FDr), who were refractory to medical therapy. The donors were family members within the second degree of kinship and were different for each transplant. Fecal characteristics were evaluated before and 12 weeks after transplantation using the Bristol stool scale (BS). BS scores of 3-5 at 12 weeks after transplantation were considered indicative of responders, while BS scores of 6 and 7 were indicative of non-responders. Metagenomic and metabolomic analyses of all 12 donor fecal samples were performed to compare the responder and non-responder groups.<br><br>RESULTS: Before transplantation, all 12 patients had BS scores of 6-7, but 12 weeks after transplantation, 6 were in the responder group and 6 were in the non-responder group. Metagenomic analysis showed that effective donor feces contained significantly higher levels of Prevotella than ineffective donor feces. Metabolomic analysis showed that effective donor feces contained significantly higher levels of propionate and butyrate and significantly lower lactate levels than ineffective donor feces.<br><br>CONCLUSION: Propionate-, butyrate-, or Prevotella-rich donor feces may contribute to successful FMT in patients with diarrhea-dominant functional gastrointestinal disorders.}, }
@article {pmid40208412, year = {2025}, author = {Sandu, AM and Chifiriuc, MC and Vrancianu, CO and Cristian, RE and Alistar, CF and Constantin, M and Paun, M and Alistar, A and Popa, LG and Popa, MI and Tantu, AC and Sidoroff, ME and Mihai, MM and Marcu, A and Popescu, G and Tantu, MM}, title = {Healthcare-Associated Infections: The Role of Microbial and Environmental Factors in Infection Control-A Narrative Review.}, journal = {Infectious diseases and therapy}, volume = {}, number = {}, pages = {}, pmid = {40208412}, issn = {2193-8229}, support = {CNFIS-FDI-2024-F-0484 INOVEX//University of Bucharest/ ; Pillar III//Ministry of Research, Innovation and Digitalization through the National Recovery and Resilience Plan (PNRR) of Romania/ ; Component C9/Investment no. 8 (I8) - contract CF 68//Ministry of Research, Innovation and Digitalization through the National Recovery and Resilience Plan (PNRR) of Romania/ ; Project No. RO1567-IBB05/2023//Institute of Biology Bucharest of the Romanian Academy/ ; project no. 23020101//The core program within the National Research Development and Innovation Plan, 2022-2027', carried out with the support of the Ministry of Research, Innovation and Digitalization (MCID),/ ; Contract no. 7N from 3 January 2023//The core program within the National Research Development and Innovation Plan, 2022-2027', carried out with the support of the Ministry of Research, Innovation and Digitalization (MCID),/ ; Dezvoltarea cercet&#x103;rii genomice &#xee;n Rom&#xe2;nia - ROGEN" (Development of genomic research in Romania -ROGEN).//ROGEN/ ; }, abstract = {Healthcare-associated infections (HAIs), previously known as nosocomial infections, represent a significant threat to healthcare systems worldwide, prolonging patient hospital stays and the duration of antimicrobial therapy. One of the most serious consequences of HAIs is the increase in the rate of antibiotic resistance (AR) generated by the prolonged, frequent, and sometimes incorrect use of antibiotics, which leads to the selection of resistant bacteria, making treatment difficult and expensive, with direct consequences for the safety of patients and healthcare personnel. Therefore, timely and accurate diagnosis of HAIs is mandatory to develop appropriate infection prevention and control practices (IPC) and new therapeutic strategies. This review aimed to present the prevalence, risk factors, current diagnosis, including artificial intelligence (AI) and machine learning approaches, future perspectives in combating HAIs causative bacteria (phage therapy, microbiome-based interventions, and vaccination), and HAIs surveillance strategies. Also, we discussed the latest findings regarding the relationships of AR with climate change and environmental pollution in the context of the One Health approach. Phage therapy is an emerging option that can offer an alternative to ineffective antibiotic treatments for antibiotic-resistant bacteria causing HAIs. Clinical trials dealing with vaccine development for resistant bacteria have yielded conflicting results. Two promising strategies, fecal microbiota transplantation and probiotic therapy, proved highly effective against recurrent Clostridium difficile infections and have been shown to reduce HAI incidence in hospitalized patients undergoing antibiotic therapy. Artificial intelligence and machine learning systems offer promising predictive capabilities in processing large volumes of clinical, microbiological, and patient data but require robust data integration. Our paper argues that HAIs are still a global challenge, requiring stringent IPC policies, computer vision, and AI-powered tools. Despite promising avenues like integrated One Health approaches, optimized phage therapy, microbiome-based interventions, and targeted vaccine development, several knowledge gaps in clinical efficacy, standardization, and pathogen complexity remain to be answered.}, }
@article {pmid40208053, year = {2025}, author = {Xu, K and Motiwala, Z and Corona-Avila, I and Makhanasa, D and Alkahalifeh, L and Khan, MW}, title = {The Gut Microbiome and Its Multifaceted Role in Cancer Metabolism, Initiation, and Progression: Insights and Therapeutic Implications.}, journal = {Technology in cancer research &amp; treatment}, volume = {24}, number = {}, pages = {15330338251331960}, pmid = {40208053}, issn = {1533-0338}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Neoplasms/metabolism/therapy/etiology/pathology/microbiology ; Disease Progression ; Animals ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {This review summarizes the intricate relationship between the microbiome and cancer initiation and development. Microbiome alterations impact metabolic pathways, immune responses, and gene expression, which can accelerate or mitigate cancer progression. We examine how dysbiosis affects tumor growth, metastasis, and treatment resistance. Additionally, we discuss the potential of microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, to modulate cancer metabolism. These interventions offer the possibility of reversing or controlling cancer progression, enhancing the efficacy of traditional treatments like chemotherapy and immunotherapy. Despite promising developments, challenges remain in identifying key microbial species and pathways and validating microbiome-targeted therapies through large-scale clinical trials. Nonetheless, the intersection of microbiome research and cancer initiation and development presents an exciting frontier for innovative therapies. This review offers a fresh perspective on cancer initiation and development by integrating microbiome insights, highlighting the potential for interdisciplinary research to enhance our understanding of cancer progression and treatment strategies.}, }
@article {pmid40207935, year = {2025}, author = {Karra, DA and Suchodolski, JS and Newman, SJ and Flouraki, E and Lidbury, JA and Steiner, JM and Xenoulis, PG}, title = {Single Enema Fecal Microbiota Transplantation in Cats With Chronic Enteropathy.}, journal = {Journal of veterinary internal medicine}, volume = {39}, number = {3}, pages = {e70054}, pmid = {40207935}, issn = {1939-1676}, mesh = {Animals ; Cats ; *Cat Diseases/therapy ; *Fecal Microbiota Transplantation/veterinary ; Female ; Male ; *Enema/veterinary ; Chronic Disease ; Prospective Studies ; Dysbiosis/veterinary/therapy ; *Intestinal Diseases/veterinary/therapy ; }, abstract = {BACKGROUND: Chronic enteropathies (CE) are common in cats, and alterations of the intestinal microbiota might be involved in the pathogenesis.<br><br>HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of a single enema fecal microbiota transplantation (FMT) in improving intestinal dysbiosis and clinical scores in cats with CE.<br><br>ANIMALS: Twenty-eight cats with either chronic inflammatory enteropathy (CIE; n&#x2009;=&#x2009;19) or small cell gastrointestinal lymphoma (SCGL; n&#x2009;=&#x2009;9) were prospectively enrolled.<br><br>METHODS: Eleven cats were randomly selected to receive a single enema FMT (FMT-group), and 17 cats were used as controls. Clinical activity was determined using the Feline Chronic Enteropathy Activity Index (FCEAI), and intestinal dysbiosis was determined using the feline dysbiosis index (DI) on the day of FMT (T0) and 30&#x2009;days after FMT (T1).<br><br>RESULTS: At T0, 14/28 cats had an abnormal DI&#x2009;>&#x2009;0. No significant difference was found in the DI from T0 to T1 in the FMT group (mean[SD]: 0.01[2.5] vs. 0.7[2.1]; p&#x2009;=&#x2009;0.47). No significant difference was found in the DI between the FMT group and the control group at T1 (mean[SD]: -0.7[2.1] vs. 0.8[1.8]; p&#x2009;=&#x2009;0.92). FCEAI significantly decreased at T1 compared to T0 in the FMT group (median[IQR] 10.0[7.7-11.3] vs. 4.5[4-5]; p&#x2009;=&#x2009;0.002). No significant difference was found in the FCEAI between the FMT group and the control group at T1 (median[IQR] 4.5[4-5] vs. 4[3-5.75]; p&#x2009;=&#x2009;0.64).<br><br>CONCLUSIONS: In this study, single enema FMT did not lead to a significant improvement in DI or FCEAI in cats with CE compared to controls.}, }
@article {pmid40207915, year = {2025}, author = {Moya Uribe, IA and Terauchi, H and Bell, JA and Zanetti, A and Jantre, S and Huebner, M and Arshad, SH and Ewart, SL and Mansfield, LS}, title = {Fecal microbiota transplants (FMT) of three distinct human communities to germ-free mice exacerbated inflammation and decreased lung function in their offspring.}, journal = {mBio}, volume = {}, number = {}, pages = {e0376424}, doi = {10.1128/mbio.03764-24}, pmid = {40207915}, issn = {2150-7511}, abstract = {UNLABELLED: Despite explosive rise in allergies, little is known about early life gut microbiota effects on postnatal respiratory function. We hypothesized that Enterobacteriaceae-dominant gut microbiota from eczemic infants increases Type 2 inflammation and decreases lung function in transplanted mice, while Bacteroidaceae-dominant gut microbiota from non-eczemic infants is protective. Fecal microbiota transplants (FMT) from eczemic infants "Infant A" and non-eczemic infants "Infant B" were successfully transplanted into germ-free C57BL/6 mice, passing to offspring unchanged. Infant A and B, Adult C-human-derived (positive control), and Mouse (negative control) microbiotas all in C57BL/6 mice were tested for effects on airway function in nonallergic (phosphate-buffered saline [PBS]) and allergic (house dust mite [HDM]) conditions. Baseline lung mechanics in mice with human microbiotas ([HU]microbiota) were significantly impaired compared to Mouse microbiota controls ([MO]microbiota) with or without HDM; respiratory system resistance (Rrs) was increased (P < 0.05-P < 0.01), and respiratory system compliance (Crs) was decreased (P < 0.05-P < 0.01). [HU]Microbiota mice showed a statistically significant impairment compared to [MO]microbiota mice in lung parameters Rrs, Ers, Rn, and G at baseline, and at multiple methacholine (MCh) doses with baseline removed. Impairment manifested as increased small airway resistance and tissue resistance. HDM significantly elevated IL-4, eosinophils, lung inflammation, and mucus cell metaplasia, and decreased macrophages and lung function (P < 0.05) in mice of all microbiotas, yet each [HU]microbiota produced distinct features. Infant B and Adult C mice had elevated basal levels of total IgE compared to [MO]microbiota and Infant A mice (P < 0.05). In [HU]microbiota mice given HDM, only Adult C had elevated IL-5 and IL-13 (P < 0.05), only Adult C and Infant B mice had elevated neutrophils (P < 0.05), and only Infant A had elevated lymphocytes (P < 0.01).<br><br>IMPORTANCE: Fecal microbiota transplants (FMT) of three distinct human communities to germ-free mice exacerbated inflammation and decreased lung function in their offspring. Taxa formerly described to induce an allergic response (agonists) and pro-inflammatory taxa were abundant in [HU]microbiotas compared to [MO]microbiota controls, while taxa formerly described to reduce allergic responses (antagonists) and anti-inflammatory taxa were numerous in [MO]microbiotas and low in [HU]microbiotas. Thus, we largely rejected our hypotheses because data supported multiple pro-inflammatory allergy agonists functioning in a community-wide fashion to impair lung function in the absence of antagonistic anti-inflammatory taxa. Structure of [HU]microbiotas played a key role in determining varied allergic responses and resulting lung impairment, yet, strikingly, all mice with [HU]microbiotas had impaired lung function even in the absence of allergens. Using a comparative approach, we showed that composition of gut microbiota can alter innate/immune regulation in the gut-lung axis to increase baseline lung function responses and the risk of allergic sensitization.}, }
@article {pmid40207909, year = {2025}, author = {Spiegelhauer, MR and Offersen, SM and Mao, X and Gambino, M and Sandris Nielsen, D and Nguyen, DN and Brunse, A}, title = {Protection against experimental necrotizing enterocolitis by fecal filtrate transfer requires an active donor virome.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2486517}, pmid = {40207909}, issn = {1949-0984}, mesh = {Animals ; *Enterocolitis, Necrotizing/prevention &amp; control/therapy/microbiology/pathology ; Swine ; Gastrointestinal Microbiome ; *Feces/virology ; *Virome/radiation effects ; *Fecal Microbiota Transplantation/methods ; Disease Models, Animal ; Animals, Newborn ; Virus Inactivation/radiation effects ; Ultraviolet Rays ; Clostridium perfringens ; Humans ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {Necrotizing enterocolitis (NEC) remains a frequent catastrophic disease in preterm infants, and fecal filtrate transfer (FFT) has emerged as a promising prophylactic therapy. This study explored the role of virome viability for the protective effect of FFT. Using ultraviolet (UV) irradiation, we established a viral inactivation protocol and administered FFT, UV-inactivated FFT (iFFT) or sterile saline orally to preterm piglets at risk for experimental NEC. The gut pathology and barrier properties were assessed, while the microbiome was explored by 16S rRNA amplicon and metavirome sequencing. Like in prior studies, FFT reduced NEC severity and intestinal inflammation, while these effects were absent in the iFFT group. Unexpectedly, piglets receiving FFT exhibited mild side effects in the form of early-onset diarrhea. The FFT also converged the gut colonization by increased viral heterogeneity and a reduced abundance of pathobionts like Clostridium perfringens and Escherichia. In contrast, the gut microbiome of iFFT recipients diverged from both FFT and the controls. These findings highlight the clear distinction between the ability of active and inactivate viromes to modulate gut microbiota and decrease pathology. The efficacy of FFT may be driven by active bacteriophages, and loss of virome activity could have consequences for the treatment efficacy.}, }
@article {pmid40207766, year = {2025}, author = {Kumar, M and Mehan, S and Sharma, T and Kumar, A and Khan, Z and Sharma, AK and Kumar, N and Gupta, GD}, title = {Integrating Gut-Brain Axis: Exploring the Neurogastrointestinal Interactions and Therapeutic Potentials in Autism Spectrum Disorder.}, journal = {Endocrine, metabolic &amp; immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303369166250325110016}, pmid = {40207766}, issn = {2212-3873}, abstract = {This comprehensive review critically examines the gut-brain axis (GBA) and its implications in autism spectrum disorder (ASD). The GBA is a complex, bidirectional communication network that integrates the gastrointestinal tract, the central nervous system, and the gut microbiota. This axis is mediated through various physiological pathways, including the enteric nervous system (ENS), the vagus nerve, immune responses, and metabolic activities of gut microorganisms. ASD, a developmental disorder marked by social impairments and repetitive behaviors, presents with notable neurological irregularities. The review highlights the increased prevalence of gastrointestinal (GI) disturbances in individuals with ASD, suggesting a potential link between GI symptoms and the severity of ASD-related behaviors. This correlation is supported by evidence of altered gut microbiota composition in ASD, indicating significant interactions between the gut environment and neurological health. Moreover, the pathophysiology of ASD is explored with an emphasis on genetic and environmental contributions to neurodevelopmental impairments. Key topics include synaptic dysfunction, the roles of neurotransmitters like GABA and serotonin, and the impact of gut-brain interactions on ASD progression. Specifically, this review addresses how gut microbiota may influence metabolic alterations, immune dysregulation, oxidative stress, mitochondrial function, and neurotransmitter production in ASD. Emerging research on microbiome-based therapies for ASD is discussed, focusing on the potential of probiotics, prebiotics, and faecal microbiota transplantation (FMT) as novel interventions. Ethical considerations in this burgeoning field are also considered, highlighting the necessity for rigorous scientific inquiry and ethical oversight. The review advocates for a multidisciplinary approach to understanding and addressing the complexities of ASD. By integrating insights from genetics, neuroscience, psychology, and gastroenterology, a more comprehensive understanding of the role of GBA in ASD can be achieved. This interdisciplinary perspective is crucial for developing effective, individualized treatments and improving the quality of life for individuals with ASD.}, }
@article {pmid40207754, year = {2025}, author = {V S, S and Prasad, C and Panicker, SP}, title = {Exploring the Role of Non-Coding RNAs in the Gut and Skin Microbiome: Implications for Colorectal Cancer and Healthy Longevity.}, journal = {MicroRNA (Shariqah, United Arab Emirates)}, volume = {}, number = {}, pages = {}, doi = {10.2174/0122115366342509250401043719}, pmid = {40207754}, issn = {2211-5374}, abstract = {In the last forty years, cancer mortality rates have risen by more than 40%, with colo-rectal cancer (CRC) ranking as the third most common kind worldwide, significantly affected by dietary factors. Restricted access to sophisticated medical treatment and insufficient comprehen-sion of colorectal cancer's biology contribute to its elevated occurrence. Researchers have recog-nized dysbiosis of the gut microbiome as a critical contributor to the development of colorectal cancer, as it influences the expression of non-coding RNAs (ncRNAs) and subsequent molecular pathways essential for tumor proliferation. Moreover, interactions between gut and skin microbi-ota can impact systemic health and ncRNA regulation, influencing CRC advancement. This study shows how important the gut-skin microbiome axis is in developing colorectal cancer. It suggests that targeting this axis may lead to new treatments, such as changing the microbiome through probiotics, prebiotics, or fecal microbiota transplantation. Nonetheless, we must address obstacles such as population heterogeneity and intricate microbiome-host interactions to facilitate the tran-sition of these medicines into clinical practice. This study seeks to elucidate the roles of dietary treatments, microbiomes, and ncRNAs in the etiology and prevention of colorectal cancer (CRC).}, }
@article {pmid40207229, year = {2025}, author = {Chen, S and Yi, M and Yi, X and Zhou, Y and Song, H and Zeng, M}, title = {Unveiling the fungal frontier: mycological insights into inflammatory bowel disease.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1551289}, pmid = {40207229}, issn = {1664-3224}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/immunology/etiology/metabolism ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology/microbiology ; *Fungi/immunology ; Animals ; *Mycoses/immunology/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal disease that seriously affects the quality of life of patients around the world. It is characterized by recurrent abdominal pain, diarrhea, and mucous bloody stools. There is an urgent need for more accurate diagnosis and effective treatment of IBD. Accumulated evidence suggests that gut microbiota plays an important role in the occurrence and development of gut inflammation. However, most studies on the role of gut microbiota in IBD have focused on bacteria, while fungal microorganisms have been neglected. Fungal dysbiosis can activate the host protective immune pathway related to the integrity of the epithelial barrier and release a variety of pro-inflammatory cytokines to trigger the inflammatory response. Dectin-1, CARD9, and IL-17 signaling pathways may be immune drivers of fungal dysbacteriosis in the development of IBD. In addition, fungal-bacterial interactions and fungal-derived metabolites also play an important role. Based on this information, we explored new strategies for IBD treatment targeting the intestinal fungal group and its metabolites, such as fungal probiotics, antifungal drugs, diet therapy, and fecal microbiota transplantation (FMT). This review aims to summarize the fungal dysbiosis and pathogenesis of IBD, and provide new insights and directions for further research in this emerging field.}, }
@article {pmid40206278, year = {2025}, author = {Cresci, GAM and Liu, Q and Sangwan, N and Liu, D and Grove, D and Shapiro, D and Ali, K and Cazzaniga, B and Prete, LD and Miller, C and Hashimoto, K and Quintini, C}, title = {The Impact of Liver Graft Preservation Method on Longitudinal Gut Microbiome Changes Following Liver Transplant: A Proof-of-concept Study.}, journal = {Journal of clinical and translational hepatology}, volume = {13}, number = {4}, pages = {284-294}, pmid = {40206278}, issn = {2310-8819}, abstract = {BACKGROUND AND AIMS: End-stage liver disease is associated with disruptions in gut microbiota composition and function, which may facilitate gut-to-liver bacterial translocation, impacting liver graft integrity and clinical outcomes following liver transplantation. This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation.<br><br>METHODS: This single-center, non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion (NMP). Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3, 6, and 12. Stool microbiota was profiled via 16S rRNA gene sequencing, stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry, and breath volatile organic compounds (VOCs) were analyzed with selected-ion flow-tube mass spectrometry.<br><br>RESULTS: Both cohorts experienced a loss of microbiota diversity and dominance by single taxa. The NMP cohort demonstrated enrichment of several beneficial gut taxa, while the static cold storage cohort showed depletion of such taxa. Various gut bacteria were found to correlate with stool short-chain fatty acids (e.g., lactic acid, butyric acid) and several VOCs.<br><br>CONCLUSIONS: Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation. However, notable differences in microbiota composition and function were observed between liver graft preservation methods. Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.}, }
@article {pmid40204291, year = {2025}, author = {Li, S and Li, J and Chen, K and Wang, J and Wang, L and Feng, C and Wang, K and Xu, Y and Gao, Y and Yan, X and Zhao, Q and Li, B and Qiu, Y}, title = {Chronic Arsenic Exposure Causes Alzheimer's Disease Characteristic Effects and the Intervention of Fecal Microbiota Transplantation in Rats.}, journal = {Journal of applied toxicology : JAT}, volume = {}, number = {}, pages = {}, doi = {10.1002/jat.4782}, pmid = {40204291}, issn = {1099-1263}, support = {202203021211246//Shanxi Natural Science Foundation of China/ ; 20240017//Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province/ ; }, abstract = {Arsenic exposure and intestinal microbiota disorders may be related with Alzheimer's disease (AD), but the mechanism has not been elucidated. This study conducted chronic arsenic exposure from rat's maternal body to adult offspring to investigate the mechanisms of the characteristic effects of chronic arsenic exposure on AD, and further explored the intervention effect of fecal microbiota transplantation (FMT) on arsenic-mediated neurotoxicity. Transmission electron microscopy, HE staining, and related indicators were measured in the control group, the exposed group, and the FMT intervention group. Western blot was used to determine microtubule-associated proteins Tau and p-Tau396, intestinal-brain barrier-related proteins Claudin-1 and Occludin, ELISA was used to detect the content of Aβ1-42, and 16S rRNA sequencing was used to detect the intestinal flora of feces. Results showed that chronic arsenic exposure could lead to neurobehavioral defects in rats, increase the expression levels of Tau, p-Tau396, and Aβ1-42 in hippocampus (p < 0.05), increase the abundance of Clostridium _ UCG-014, decrease the abundance of Roseburia, and decrease the expression levels of Claudin-1 and Occludin in colon and hippocampus (p < 0.05). After FMT intervention, the expression levels of Tau and p-Tau396 were decreased (p < 0.05), and the abundance of Roseburia was increased. In summary, chronic arsenic exposure caused intestinal flora disorder by changing the abundance of inflammation-related flora, thereby destroying the gut-brain barrier and causing AD characteristic effects in rats. Although the bacterial specific genus was improved and the expression of AD-related proteins was reduced after transplantation, it could not alleviate the neurobehavioral defects and neurotoxicity caused by arsenic exposure.}, }
@article {pmid40203217, year = {2025}, author = {Randolph, NK and Salerno, M and Klein, H and Diaz-Campos, D and van Balen, JC and Winston, JA}, title = {Preparation of Fecal Microbiota Transplantation Products for Companion Animals.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0319161}, pmid = {40203217}, issn = {1932-6203}, support = {T35 OD010977/OD/NIH HHS/United States ; }, mesh = {Animals ; Dogs ; Cats ; *Fecal Microbiota Transplantation/methods/veterinary ; *Feces/microbiology ; *Pets/microbiology ; Microbial Viability ; }, abstract = {Fecal microbiota transplantation (FMT) is increasingly utilized in small animal medicine for the treatment of a variety of gastrointestinal and non-gastrointestinal disorders. Despite proven clinical efficacy, there is no detailed protocol available for the preparation and storage of FMT products for veterinarians in a variety of clinical settings. Herein, the effect of processing technique on the microbial community structure was assessed with amplicon sequence analysis. Microbial viability was assessed with standard culture techniques using selective media. Given the fastidious nature of many intestinal microbes, colony forming units are considered surrogate viable microbes, representing a portion of potentially viable microbes. FMT products from four screened canine fecal donors and six screened feline fecal donors were processed aerobically according to a double centrifugation protocol adapted from the human medical literature. Fresh feces from an additional three screened canine fecal donors were used to evaluate the effect of cryopreservative, centrifugation, and short-term storage on microbial community structure and in vitro surrogate bacterial viability. Finally, fresh feces from a third group of three screened canine and three screened feline fecal donors were used to evaluate the long-term in vitro surrogate bacterial viability of three frozen and lyophilized FMT products. Microbiota analysis revealed that each canine fecal donor has a unique microbial profile. Processing of canine and feline feces for FMT does not significantly alter the overall microbial community structure. The addition of cryopreservatives and lyopreservatives significantly improved long-term viability, up to 6 months, for frozen and lyophilized FMT products compared to unprocessed raw feces with no cryopreservative. These results prove the practicality of this approach for FMT preparation in veterinary medicine and provide a detailed protocol for researchers and companion animal practitioners. Future in vivo research is needed to evaluate how the preparation and microbial viability of FMT impacts the recipient's microbial community and clinical outcomes across multiple disease phenotypes.}, }
@article {pmid40202719, year = {2025}, author = {Huang, Z and Liu, C and Zhao, X and Guo, Y}, title = {The effect of elevated levels of the gut metabolite TMAO on glucose metabolism after sleeve gastrectomy.}, journal = {Archives of physiology and biochemistry}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/13813455.2025.2489721}, pmid = {40202719}, issn = {1744-4160}, abstract = {Purpose：Bariatric surgery can effectively alleviate obesity and diabetes by regulation of the gut microbiota. This study aimed to investigate the change in the gut microbiota metabolite TMAO and to explore its effect on glucose metabolism after sleeve gastrectomy (SG). Materials and methods：Diet-induced obesity mouse models were established, and the mice were randomly divided into four groups: an SG group, a sham-operated group pair-fed with the SG group (PF), a sham-operated group fed ad libitum (AL), and a lean control group (C). At 10 weeks post-surgery, the changes in glycogen content of liver, gut microbiota and the level of FMO3 in the liver were evaluated, and their correlation with TMAO production was analysed. The expression levels of the TMAO/PERK/FOXO1 pathway and the gluconeogenic genes G6PC and PCK1 were measured. Results：At 10 weeks post-surgery, hepatocyte glycogen levels were restored, and serum TMA and TMAO levels were significantly increased. Faecal metagenomic sequencing results showed that the abundances of Ruminococcaceae and Lachnospiraceae, which were positively correlated with TMAO production, were significantly increased after surgery. While the changes in FMO3, the key enzyme producing TMAO in the liver was found decreased significantly after SG. The expression levels of the TMAO/PERK/FOXO1 pathway and the gluconeogenic genes G6PC and PCK1 were measured. Inconsistent with the changing trend of TMAO, the expression of PERK, FOXO1, PCK, and G6PC significantly decreased after SG. Conclusions：SG can significantly reduce obesity and restore glucose metabolism. After surgery, TMAO metabolites increased in a microbiota-dependent manner.}, }
@article {pmid40202676, year = {2025}, author = {Sharma, S and Tiwari, N and Tanwar, SS}, title = {The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {40202676}, issn = {1432-1912}, abstract = {Recent research has highlighted the complex relationship between gut microbiota, metabolic pathways, and nonalcoholic fatty liver disease (NAFLD) progression. Gut dysbiosis, commonly observed in NAFLD patients, impairs intestinal permeability, leading to the translocation of bacterial products like lipopolysaccharides, short-chain fatty acids, and ethanol to the liver. These microbiome-associated mechanisms contribute to intestinal and hepatic inflammation, potentially advancing NAFLD to NASH. Dietary habits, particularly those rich in saturated fats and fructose, can modify the microbiome composition, leading to dysbiosis and fatty liver development. Metabolomic approaches have identified unique profiles in NASH patients, with specific metabolites like ethanol linked to disease progression. While bariatric surgery has shown promise in preventing NAFLD progression, the role of gut microbiome and metabolites in this improvement remains to be proven. Understanding these microbiome-related pathways may provide new diagnostic and therapeutic targets for NAFLD and NASH. A comprehensive review of current literature was conducted using multiple medical research databases, including PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, ScienceDirect, Medline, ProQuest, and Google Scholar. The review focused on studies that examine the relationship between gut microbiota composition, metabolic pathways, and NAFLD progression. Key areas of interest included microbial dysbiosis, endotoxin production, and the influence of diet on gut microbiota. The analysis revealed that gut dysbiosis contributes to NAFLD through several mechanisms, diet significantly influences gut microbiota composition, which in turn affects liver function through the gut-liver axis. High-fat diets can lead to dysbiosis, altering microbial metabolic activities and promoting liver inflammation. Specifically, gut microbiota-mediated generation of saturated fatty acids, such as palmitic acid, can activate liver macrophages and increase TNF-α expression, contributing to NASH development. Different dietary components, including cholesterol, fiber, fat, and carbohydrates, can modulate the gut microbiome and influence NAFLD progression. This gut-liver axis plays a crucial role in maintaining immune homeostasis, with the liver responding to gut-derived bacteria by activating innate and adaptive immune responses. Microbial metabolites, such as bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis, contributing to NASH pathogenesis. Additionally, the microbiome of NASH patients shows an elevated capacity for alcohol production, suggesting similarities between alcoholic steatohepatitis and NASH. These findings indicate that targeting the gut microbiota may be a promising approach for NASH treatment and prevention. Recent research highlights the potential of targeting gut microbiota for managing nonalcoholic fatty liver disease (NAFLD). The gut-liver axis plays a crucial role in NAFLD pathophysiology, with dysbiosis contributing to disease progression. Various therapeutic approaches aimed at modulating gut microbiota have shown promise, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Probiotics have demonstrated efficacy in human randomized controlled trials, while other interventions require further investigation in clinical settings. These microbiota-targeted therapies may improve NAFLD outcomes through multiple mechanisms, such as reducing inflammation and enhancing metabolic function. Although lifestyle modifications remain the primary recommendation for NAFLD management, microbiota-focused interventions offer a promising alternative for patients struggling to achieve weight loss targets.}, }
@article {pmid40201970, year = {2025}, author = {Chen, Y and Zeng, Y and Zhang, Y and Chen, J and Qian, Y and Huang, J and Chen, G and Xia, G and Wang, C and Feng, A and Nie, X}, title = {Differential gut microbiota and inflammatory cytokines contribute to IgA vasculitis.}, journal = {Clinical and experimental rheumatology}, volume = {43}, number = {4}, pages = {563-574}, doi = {10.55563/clinexprheumatol/ff61t7}, pmid = {40201970}, issn = {0392-856X}, mesh = {*Gastrointestinal Microbiome/immunology ; Humans ; Animals ; Male ; Female ; Child ; *Immunoglobulin A/immunology/blood ; *Cytokines/blood/immunology ; *Dysbiosis/immunology ; *IgA Vasculitis/microbiology/immunology/blood/diagnosis ; Case-Control Studies ; Mice ; *Inflammation Mediators/blood ; Disease Models, Animal ; *Bacteria/immunology/genetics ; Adolescent ; Child, Preschool ; Fecal Microbiota Transplantation ; }, abstract = {OBJECTIVES: Immunoglobulin A vasculitis (IgAV) is the most common form of vasculitis in childhood. Emerging evidence indicates that gut microbiota plays a key role in the pathogenesis of IgAV. However, the factors linking gut microbiota to the onset and progression of IgAV are poorly understood. We aimed to demonstrate that the presence of a specific dysbiosis in patients with IgAV contributes to the onset of IgAV.<br><br>METHODS: We transplanted gut microbiota from human donors with IgAV or healthy controls (HCs). The changes in gut microbiota and serum indexes of the recipient mice were detected, and the IgAV-associated bacteria were determined by integrating the results from the mouse sequence data analysis with the human sequence results.<br><br>RESULTS: 55 amplicon sequence variants (ASVs) specific to IgAV children were detected in the recipient IgAV microbiota (rIMb) mice, and 35 ASVs specific to healthy children were detected in the recipient healthy microbiota (rHMb) mice. Gut microbiota in rIMb mice differs from that in rHMb mice. Alcaligenaceae could discriminate rIMb from rHMb mice, while its abundance was decreased in rIMb compared to rHMb (p<0.05). In children with IgAV, the abundance of Burkholderiaceae (Alcaligenaceae accounted for 99.7%) at the family level was significantly lower compared to HCs, which can be used to distinguish children with IgAV from HCs, and the constructed receiver operating characteristic (ROC) curve had an area under the curve (AUC) value of 0.766. In addition, the rIMb group had a markedly higher interleukin (IL)-17A and IL-21 level than those in the rHMb group. The Spearman correlation analysis indicated significant correlations between the relative levels of these pro-inflammatory cytokines, IgA and alterations of gut microbiota.<br><br>CONCLUSIONS: IgAV is characterised by disturbances of gut microbiota composition and an imbalance in inflammatory cytokines. The manipulation of gut microbiota could be a possible way to prevent and manage IgAV.}, }
@article {pmid40201831, year = {2025}, author = {Dewey, CW}, title = {Poop for thought: Can fecal microbiome transplantation improve cognitive function in aging dogs?.}, journal = {Open veterinary journal}, volume = {15}, number = {2}, pages = {556-564}, pmid = {40201831}, issn = {2218-6050}, mesh = {Dogs ; Animals ; *Fecal Microbiota Transplantation/veterinary ; *Dog Diseases/therapy/microbiology ; Dysbiosis/therapy/veterinary ; Gastrointestinal Microbiome ; *Aging ; *Cognitive Dysfunction/therapy ; Cognition ; *Alzheimer Disease/therapy/veterinary ; Humans ; }, abstract = {Canine cognitive dysfunction (CCD) is the dog version of human Alzheimer's disease (AD), and it has strikingly similar pathological features to those of this neurodegenerative disorder. The gastrointestinal system is in constant communication with the brain via several conduits collectively termed the gut-brain axis. The microbial population of the gut, referred to as the microbiota, has a profound effect on the interactions that occur along this communication route. Recent evidence suggests that dysbiosis, an abnormal gastrointestinal microbial population, is linked to cognitive impairment in rodent AD models and human AD. There is also evidence from rodent AD models that correcting dysbiosis by transferring fecal material from healthy donors to the gastrointestinal tracts of cognitively impaired recipients [fecal microbiome transplantation (FMT)] reverses AD-associated brain pathology and improves cognitive function. Although limited, some clinical reports have described the improvement of cognitive function with FMT in human AD. The goals of this review article are to provide an overview of the mechanisms involved in dysbiosis- associated cognitive decline and the role of FMT in therapy for such decline. The potential role of FMT in CCD is also discussed.}, }
@article {pmid40201444, year = {2025}, author = {Liu, Y and Li, X and Chen, Y and Yao, Q and Zhou, J and Wang, X and Meng, Q and Ji, J and Yu, Z and Chen, X}, title = {Fecal microbiota transplantation: application scenarios, efficacy prediction, and factors impacting donor-recipient interplay.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1556827}, pmid = {40201444}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) represents a therapeutic approach that directly regulates the gut microbiota of recipients, normalizes its composition and reaping therapeutic rewards. Currently, in addition to its general application in treating Clostridium difficile (C. difficile) infection (CDI), FMT treatment has also been extended to the fields of other gastrointestinal diseases, infections, gut-liver or gut-brain axis disorders, metabolic diseases and cancer, etc. Prior to FMT, rigorous donor screening is essential to reduce the occurrence of adverse events. In addition, it is imperative to evaluate whether the recipient can safely and effectively undergo FMT treatment. However, the efficacy of FMT is influenced by the complex interactions between the gut microbiota of donor and recipient, the degree of donor microbiota engraftment is not necessarily positively related with the success rate of FMT. Furthermore, an increasing number of novel factors affecting FMT outcomes are being identified in recent clinical trials and animal experiments, broadening our understanding of FMT treatment. This article provides a comprehensive review of the application scenarios of FMT, the factors influencing the safety and efficacy of FMT from the aspects of both the donors and the recipients, and summarizes how these emerging novel regulatory factors can be combined to predict the clinical outcomes of patients undergoing FMT.}, }
@article {pmid40200137, year = {2025}, author = {Wang, X and Geng, Q and Jiang, H and Yue, J and Qi, C and Qin, L}, title = {Fecal microbiota transplantation enhanced the effect of chemoimmunotherapy by restoring intestinal microbiota in LLC tumor-bearing mice.}, journal = {BMC immunology}, volume = {26}, number = {1}, pages = {30}, pmid = {40200137}, issn = {1471-2172}, support = {CJ20220086//Changzhou 8th Batch of Science and Technology Project (Applied Basic Research)/ ; CMCC202201//Clinical Research Project of Changzhou Medical Center, Nanjing Medical University/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; *Fecal Microbiota Transplantation/methods ; Mice ; *Carcinoma, Lewis Lung/therapy/immunology/microbiology ; Mice, Inbred C57BL ; *Immunotherapy/methods ; RNA, Ribosomal, 16S/genetics ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology ; }, abstract = {OBJECTIVE: To assess the effect of half-dose chemotherapy (HDC) and standard-dose chemotherapy (SDC) on the intestinal microbiota and to investigate whether fecal microbiota transplantation (FMT) can restore the intestinal microecology to enhance the efficacy of chemoimmunotherapy containing an anti-PD- 1 antibody (PD1).<br><br>METHODS: Lewis lung cancer (LLC) tumor-bearing mice were divided into six groups, including Control, HDC, SDC, SDC +&#x2009;FMT, SDC +&#x2009;PD1, and SDC +&#x2009;PD1 +&#x2009;FMT. After the treatment, analyses were conducted on intestinal microbiota using 16S rRNA sequencing, immune cells through flow cytometry, cytokines and chemokines via polymerase chain reaction (PCR), and programmed death-ligand 1 (PD-L1) expression in tumor tissues by immunohistochemistry.<br><br>RESULTS: Alpha and beta diversity of intestinal flora were not significantly different between HDC and SDC groups, nor was there a significant difference in the abundance of the top 10 species at the phylum, class, order, family, genus, or species levels. FMT increased both alpha and beta diversity and led to an increase in the abundance of Ruminococcus_callidus and Alistipes_finegoldii at the species level in mice receiving SDC +&#x2009;FMT. Besides, tumor growth was significantly slowed in SDC +&#x2009;PD1 +&#x2009;FMT compared to SDC +&#x2009;PD1 group, accompanied by an up-regulated Bacteroidetes/Firmicutes ratio, down-regulated abundance of Proteobacteria species (including Pseudolabrys, Comamonas, Alcaligenaceae, Xanthobacteraceae and Comamonadaceae), as well as Faecalicoccus of Firmicutes, the increased number of cDC1 cells, cDC2 cells, CD4[+] T cells and CD8[+] T cells in the peripheral blood, and IFN-&#x3b3;[+]CD8[+] T cells, IFN-&#x3b3;, granzyme B, TNF-&#x3b1;, CXCL9 and CXCL10 in intestinal tissues.<br><br>CONCLUSIONS: There were no significant differences between HDC and SDC in their effects on the intestinal microbiota. FMT exhibited a beneficial impact on gut microbiota and improved the efficacy of chemoimmunotherapy, possibly associated with the increase of immune cells and the modulation of related cytokines and chemokines.}, }
@article {pmid40199985, year = {2025}, author = {Vecchiato, CG and Sabetti, MC and Sung, CH and Sportelli, F and Delsante, C and Pinna, C and Alonzo, M and Erba, D and Suchodolski, JS and Pilla, R and Pietra, M and Biagi, G and Procoli, F}, title = {Effect of faecal microbial transplantation on clinical outcome, faecal microbiota and metabolome in dogs with chronic enteropathy refractory to diet.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {11957}, pmid = {40199985}, issn = {2045-2322}, mesh = {Animals ; Dogs ; *Fecal Microbiota Transplantation/methods ; *Metabolome ; Male ; Female ; *Feces/microbiology ; *Dog Diseases/therapy/microbiology/metabolism ; Treatment Outcome ; Gastrointestinal Microbiome ; *Intestinal Diseases/therapy/veterinary/microbiology ; Chronic Disease ; Diet ; Bile Acids and Salts/metabolism ; Dysbiosis/therapy ; }, abstract = {Chronic enteropathy (CE) is a common complaint in canine gastroenterology. Recently, faecal microbiota transplantation (FMT) gained attention as a treatment strategy. However, the efficacy and long-term impact of FMT is still unclear. Clinical index (CIBDAI), faecal microbiota and metabolome were monitored in 20 CE dogs refractory to diet before (T0) and 3 months (T3) after FMT. Further data were retrospectively collected up to 1-year after FMT. Significant improvements were observed in CIBDAI, Dysbiosis Index (DI), and primary (PBAs) and secondary (SBAs) faecal bile acids and propionate one month (T1) after FMT (CIBDAI (median and range): T0 5 (1-9) vs. T1 1 (0-5), p < 0.0001; DI (median and range): T0 -0.1 (-5.6 to 3.8) vs. T1 -2.1 (-5.7 to 4.7), p < 0.05; PBAs decreased by 57%, SBAa increased by 41%; propionate increased by 20%). According to CIBDAI, 17 dogs clinically improved up to T3, and 10 dogs remained clinically stable up to one year after FMT. Alpha- and beta-diversity of the faecal microbiota of CE dogs did not differ, neither before nor after FMT, from that of 17 healthy controls. The results highlight that CE dogs refractory to diet with mild clinical signs and dysbiosis may benefit long-term from treatment with FMT.}, }
@article {pmid40199868, year = {2025}, author = {Liu, C and Zheng, X and Ji, J and Zhu, X and Liu, X and Liu, H and Guo, L and Ye, K and Zhang, S and Xu, YJ and Sun, X and Zhou, W and Wong, HLX and Tian, Y and Qian, H}, title = {The carotenoid torularhodin alleviates NAFLD by promoting Akkermanisa muniniphila-mediated adenosylcobalamin metabolism.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3338}, pmid = {40199868}, issn = {2041-1723}, mesh = {Animals ; *Carotenoids/pharmacology ; Male ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism/microbiology ; Mice ; Humans ; Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; *Akkermansia/metabolism/drug effects ; Liver/metabolism/drug effects/pathology ; Disease Models, Animal ; *Vitamin B 12/metabolism/analogs &amp; derivatives ; Colon/metabolism/drug effects ; }, abstract = {Torularhodin, a unique carotenoid, confers beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the precise mechanism underlying its therapeutic effects remains unknown. Here, we report that torularhodin alleviates NAFLD in male mice by modulating the gut microbiota. Additionally, transplanting fecal microbiota from torularhodin-treated mice to germ-free mice also improves NAFLD. Mechanistically, torularhodin specifically enriches the abundance of Akkermansia muciniphila, which alleviates NAFLD by promoting the synthesis of adenosylcobalamin. Utilizing a human gastrointestinal system and a colonic organoid model, we further demonstrate that adenosylcobalamin confers protective effects against NAFLD through reducing ceramides, a well-known liver damaging compound, and this effect is mediated by inhibition of the hypoxia-inducible factor 2α pathway. Notably, we construct electrospun microsphere-encapsulated torularhodin, which facilitates the slow release of torularhodin in the colon. Together, our findings indicate the therapeutic potential of microbial utilization of carotenoids, such as torularhodin, for treating NAFLD.}, }
@article {pmid40198451, year = {2025}, author = {Duo, R and Wang, Y and Ma, Q and Wang, X and Zhang, Y and Shen, H}, title = {MTX-induced gastrointestinal reactions in RA: Prevotella enrichment, gut dysbiosis, and PI3K/Akt/Ras/AMPK pathways.}, journal = {Clinical rheumatology}, volume = {}, number = {}, pages = {}, pmid = {40198451}, issn = {1434-9949}, support = {No. CY2023-MS-A13//CuiYing Technology Project of Lanzhou University/ ; No. 2023-4-27//Science and Technology Planning Project of Lanzhou/ ; No. 2018-3-49//Science and Technology Planning Project of Lanzhou/ ; No. CYXZ2022-13//Cuiying Scientific Training Program for Undergraduates of The Second Hospital &amp; Clinical Medical School/ ; 25JRRA617//Natural Science Foundation of Gansu Province/ ; 2025B-020//Gansu Province Higher Education Institution Teachers' Innovation Fund Project/ ; }, abstract = {OBJECTIVES: To investigate the role of gut microbiota in methotrexate (MTX)-induced gastrointestinal reactions (MRGR) in patients with rheumatoid arthritis (RA).<br><br>METHODS: As a prospective, single-center, convenience sampling study, stool samples were obtained from 28 RA patients (male: female&#x2009;=&#x2009;10:18) at Lanzhou University Second Hospital who were undergoing MTX treatment for analysis of their gut microbiota using 16S rRNA gene sequencing. Clinical disease activity (CDAI) and MRGR were assessed after two months of MTX therapy. All data collection periods exceeded one year. Intestinal germ-free mice, generated through antibiotic treatment, received fecal microbiota transplantation (FMT) from the patients, followed by varying doses of MTX to observe MRGR. Intestinal transcriptomics and markers related to intestinal barrier function were subsequently examined.<br><br>RESULTS: Females (84.6%) and high disease activity (CDAI scores, 39.6&#x2009;&#xb1;&#x2009;11.2 vs 26.3&#x2009;&#xb1;&#x2009;9.2) were prone to have MRGR in RA patients. Patients with MRGR (PT-GR) showed lower gut microbial diversity versus non-MRGR (PT-noGR).&#xa0;Prevotella&#xa0;abundance, positively correlated with CDAI and MRGR (p&#x2009;<&#x2009;0.05), was elevated in PT-GR. Administering 10&#xa0;mg/kg MTX to mice caused intestinal damage. FMT-GR-MTX mice exhibited weight loss (95.2%), morphological deterioration (86.4%), and reduced tight junction proteins (Claudin-1:72.4%; ZO-1:81.2%). Transcriptomics linked upregulated G&#x3b2;&#x3b3;/CREB/Atp4b to PI3K/Akt/Ras pathways and downregulated PFK2/PP2 to AMPK signaling in MRGR.<br><br>CONCLUSION: Our study identified notable gut microbiota alterations in RA patients prone to MRGR, with changes in intestinal gene expression and reduced intestinal barrier function potentially contributing to MRGR. These findings suggest potential strategies to mitigate MRGR in RA patients undergoing MTX treatment. Key Points &#x2022; The RA-related MRGR is correlated with the intestinal microbiota. &#x2022; Females, low gut diversity, and Prevotella enrichment are MRGR risks in RA. &#x2022; Upregulated DEGs in MRGR linked to PI3K/Akt, Ras pathways. &#x2022; Downregulated DEGs in MRGR focus on the AMPK pathway.}, }
@article {pmid40198007, year = {2025}, author = {Attauabi, M and Madsen, GR and Holm, JP and Bendtsen, F and Møller, S and Seidelin, JB and Burisch, J}, title = {Incidence of Osteoporosis and Osteopenia in Newly Diagnosed Inflammatory Bowel Disease: A Population-Based Cohort Study.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf063}, pmid = {40198007}, issn = {1536-4844}, support = {//Novo Nordisk Fonden/ ; 101095470//EU Horizon Europe Program/ ; }, abstract = {BACKGROUND: Individuals with Crohn's disease (CD) and ulcerative colitis (UC) are at risk of developing osteoporosis. In Denmark, osteoporosis has been observed in 12.0% of postmenopausal women and 2.6% in men aged ≥ 50 years in the general population. We aimed to conduct a population-based analysis determining bone mineral density (BMD) at diagnosis of UC and CD.<br><br>METHODS: All adult patients diagnosed with UC or CD between May 2021 and May 2023 in an area covering 20% (1.2 million inhabitants) of the Danish population were invited for dual-energy X-ray absorptiometry at inflammatory bowel disease (IBD) diagnosis.<br><br>RESULTS: In total, 209 and 141 patients with UC and CD, respectively, were included. Among postmenopausal women (age&#x2005;&#x2265;&#x2005;52 years) with UC, 15/42 (35.7%) had osteoporosis and 17/42 (40.5%) had osteopenia, while rates among patients with CD were 6/21 (28.6%, P&#x2005;=&#x2005;.57) and 8/21 (38.1%, P&#x2005;=&#x2005;.86), respectively. Among males aged&#x2005;&#x2265;&#x2005;50 years, the rates were 5/38 (13.2%) and 17/38 (44.7%) in UC, respectively, and 3/24 (12.5%, P&#x2005;=&#x2005;1.00) and 12/24 (50.0%, P&#x2005;=&#x2005;.69) in CD, respectively. Among younger patients, BMD below the expected range for age was observed in 3/69 (4.3%) and 3/60 (5.0%) of females and males with UC, and in 1/42 (2.4%) and 8/54 (14.8%) with CD, respectively. No nutritional or inflammatory marker, including C-reactive protein, fecal calprotectin, Mayo Endoscopic Score, or Simple Endoscopic Score for CD correlated with the T-score.<br><br>CONCLUSIONS: This population-based study demonstrated high rates of osteoporosis among postmenopausal women and males aged&#x2005;&#x2265;&#x2005;50 years at IBD diagnosis, highlighting the need for systematic evaluation in these patients.}, }
@article {pmid40197991, year = {2025}, author = {Malard, F and Thepot, S and Cluzeau, T and Carre, M and Lebon, D and Bories, P and Legrand, O and Schwarz, M and Loschi, M and Meunier, M and Joris, M and Gasc, C and Jouve, J and Levast, B and Plantamura, E and Prestat, E and Sabourin, A and Gaugler, B and Dore, J and Récher, C and Mohty, M}, title = {Gut microbiota restoration with oral pooled fecal microbiotherapy after intensive chemotherapy: the phase Ib CIMON trial.}, journal = {Blood advances}, volume = {}, number = {}, pages = {}, doi = {10.1182/bloodadvances.2024015571}, pmid = {40197991}, issn = {2473-9537}, abstract = {Intensive chemotherapy (IC) combined with broad-spectrum antibiotics for acute myeloid leukemia (AML) leads to gut microbiota dysbiosis, promoting pathological conditions and an increased incidence of complications, possibly limiting eligibility to allogenic hematopoietic cell transplantation (alloHCT). The purpose of this dose-ranging phase I study (CIMON) was to evaluate the first-in-man use of MaaT033, a pooled, allogeneic, lyophilized, and standardized fecal microbiotherapeutic product, formulated as a delayed-release capsule for oral administration. Primary objectives of the study were to evaluate the maximum tolerable dose of MaaT033 in 21 AML patients having undergone IC and antibiotics. Secondary objectives were to assess MaaT033 safety, its efficacy in restoring the patients' gut microbiome using shotgun sequencing in order to evaluate the recommended dose regimen, and patient compliance (ClinicalTrials.gov number: NCT04150393). MaaT033 was shown to be safe and effective for gut microbiota restoration in AML patients receiving IC and antibiotics, with an excellent gut microbiota reconstruction based on diversity indices at the species level, and restoration of microbial communities close to the composition of the drug product. Moreover, inflammatory markers (C-reactive protein, interleukin-6) decrease with treatment, while short-chain fatty acids increase over time. A randomized, placebo-controlled phase IIb trial, in recipients of alloHCT patients in ongoing.}, }
@article {pmid40196486, year = {2025}, author = {Shealy, NG and Baltagulov, M and de Brito, C and McGovern, A and Castro, P and Schrimpe-Rutledge, AC and Malekshahi, C and Condreanu, SG and Sherrod, SD and Jana, S and Jones, K and Ribeiro, TM and McLean, JA and Beiting, DP and Byndloss, MX}, title = {Short-term alterations in dietary amino acids override host genetic susceptibility and reveal mechanisms of Salmonella Typhimurium small intestine colonization.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40196486}, issn = {2692-8205}, support = {R01 AI168302/AI/NIAID NIH HHS/United States ; R01 DK131104/DK/NIDDK NIH HHS/United States ; T32 ES007028/ES/NIEHS NIH HHS/United States ; }, abstract = {In addition to individual genetics, environmental factors (e.g., dietary changes) may influence host susceptibility to gastrointestinal infection through unknown mechanisms. Herein, we developed a model in which CBA/J mice, a genetically resistant strain that tolerates intestinal colonization by the enteric pathogen Salmonella Typhimurium (S. Tm), rapidly succumb to infection after exposure to a diet rich in L-amino acids (AA). In mice, S. Tm-gastroenteritis is restricted to the large intestine (cecum), limiting their use to understand S. Tm small intestine (ileum) colonization, a feature of human Salmonellosis. Surprisingly, CBA mice fed AA diet developed ileitis with enhanced S. Tm ileal colonization. Using germ-free mice and ileal-fecal slurry transplant, we found diet-mediated S. Tm ileal expansion to be microbiota-dependent. Mechanistically, S. Tm relied on Fructosyl-asparagine utilization to expand in the ileum during infection. We demonstrate how AA diet overrides host genetics by altering the gut microbiota's ability to prevent S. Tm ileal colonization.}, }
@article {pmid40195995, year = {2025}, author = {Ayayee, P and Custer, G and Clayton, JB and Price, J and Ramer-Tait, A and Larsen, T}, title = {Assessing gut microbial provisioning of essential amino acids to host in a murine model with reconstituted gut microbiomes.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40195995}, issn = {2693-5015}, support = {K01 OD030514/OD/NIH HHS/United States ; P20 GM103427/GM/NIGMS NIH HHS/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; }, abstract = {Gut microbial essential amino acid (EAA) provisioning to mammalian hosts remains a critical yet poorly understood aspect of host-microbe nutritional interactions, with significant implications for human and animal health. To investigate microbial EAA contributions in mice with reconstituted gut microbiomes, we analyzed stable carbon isotopes ([13]C) of six EAAs across multiple organs. Germ-free (GF) mice fed a high-protein diet (18%) were compared to conventionalized (CVZ) mice fed a low-protein diet (10%) following fecal microbiota transplantation 30 days prior and a 20-day dietary intervention. We found no evidence for microbial EAA contributions to host tissues, with [13]C-EAA fingerprinting revealing nearly identical patterns between GF and CVZ organs. Both groups maintained their expected microbiome statuses, with CVZ gut microbiota dominated by Firmicutes and Bacteroidetes phyla. These findings raise important questions about the functional capacities of reconstituted gut microbiomes. Future studies should investigate longer adaptation periods, varied dietary protein levels, and complementary analytical techniques to better understand the context-dependent nature of microbial EAA provisioning in mammalian hosts.}, }
@article {pmid40195644, year = {2025}, author = {Barrios Steed, D and Koundakjian, D and Harris, AD and Rosato, AE and Konstantinidis, KT and Woodworth, MH}, title = {Leveraging strain competition to address antimicrobial resistance with microbiota therapies.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2488046}, pmid = {40195644}, issn = {1949-0984}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; R38 AI174306/AI/NIAID NIH HHS/United States ; U54 CK000601/CK/NCEZID CDC HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Anti-Bacterial Agents/pharmacology ; *Bacteria/drug effects/genetics/growth &amp; development ; Fecal Microbiota Transplantation ; *Drug Resistance, Bacterial ; Animals ; Probiotics ; }, abstract = {The enteric microbiota is an established reservoir for multidrug-resistant organisms that present urgent clinical and public health threats. Observational data and small interventional studies suggest that microbiome interventions, such as fecal microbiota products and characterized live biotherapeutic bacterial strains, could be an effective antibiotic-sparing prevention approach to address these threats. However, bacterial colonization is a complex ecological phenomenon that remains understudied in the context of the human gut. Antibiotic resistance is one among many adaptative strategies that impact long-term colonization. Here we review and synthesize evidence of how bacterial competition and differential fitness in the context of the gut present opportunities to improve mechanistic understanding of colonization resistance, therapeutic development, patient care, and ultimately public health.}, }
@article {pmid40192235, year = {2025}, author = {Jiao, Y and Ren, J and Xie, S and Yuan, N and Shen, J and Yin, H and Wang, J and Guo, H and Cao, J and Wang, X and Wu, D and Zhou, Z and Qi, X}, title = {Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2488105}, pmid = {40192235}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/radiation effects ; *Bile Acids and Salts/metabolism ; Mice ; *NF-kappa B/metabolism/genetics ; Signal Transduction/radiation effects ; *Raffinose/metabolism ; Mice, Inbred C57BL ; Whole-Body Irradiation/adverse effects ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Fecal Microbiota Transplantation ; Male ; *Acute Radiation Syndrome/microbiology/metabolism ; *Hematopoiesis/radiation effects ; *Bacteria/metabolism/genetics/classification/isolation &amp; purification ; Dysbiosis/microbiology ; }, abstract = {Radiation-associated hematopoietic recovery (RAHR) is critical for mitigating lethal complications of acute radiation syndrome (ARS), yet therapeutic strategies remain limited. Through integrated multi-omics analysis of a total body irradiation (TBI) mouse model, we identify Bacteroides acidifaciens-dominated gut microbiota as key mediators of RAHR impairment. 16S ribosomal rRNA sequencing revealed TBI-induced dysbiosis characterized by Bacteroidaceae enrichment, while functional metagenomics identified raffinose metabolism as the most significantly perturbed pathway. Notably, raffinose supplementation (10% w/v) recapitulated radiation-induced microbiota shifts and delayed bone marrow recovery. Fecal microbiota transplantation (FMT) revealed a causative role for raffinose-metabolizing microbiota, particularly Bacteroides acidifaciens, in delaying RAHR progression. Mechanistically, B. acidifaciens-mediated bile acid deconjugation activated FXR, subsequently suppressing NF-κB-dependent hematopoietic recovery. Therapeutic FXR inhibition via ursodeoxycholic acid (UDCA) had been shown to be a viable method for rescuing RAHR. Our results delineated a microbiome-bile acid-FXR axis as a master regulator of post-irradiation hematopoiesis. Targeting B. acidifaciens or its metabolic derivatives could represent a translatable strategy to mitigate radiation-induced hematopoietic injury.}, }
@article {pmid40192143, year = {2025}, author = {Feuerstadt, P and Allegretti, J and Khanna, S}, title = {Treatment of Clostridioides difficile : The Times They Are Changing.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000003445}, pmid = {40192143}, issn = {1572-0241}, }
@article {pmid40192074, year = {2025}, author = {Geng, L and Yang, X and Sun, J and Ran, X and Zhou, D and Ye, M and Wen, L and Wang, R and Chen, M}, title = {Gut Microbiota Modulation by Inulin Improves Metabolism and Ovarian Function in Polycystic Ovary Syndrome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2412558}, doi = {10.1002/advs.202412558}, pmid = {40192074}, issn = {2198-3844}, support = {23Y11909600//Science and Technology Commission of Shanghai Municipality/ ; 1365//Talent reservoir program of Shanghai First Maternity and Infant Hospital/ ; 81871213//National Natural Science Foundation of China/ ; 81671468//National Natural Science Foundation of China/ ; SHDC2020CR4080//Shanghai Municipal Hospital Development Center/ ; 2021ScienceandTechnology02-37//Shanghai Collaborative Innovation Center for Chronic Disease Prevention and Health Services/ ; }, abstract = {The management of metabolic disorder associated with polycystic ovary syndrome (PCOS) has been suggested as an effective approach to improve PCOS which is highly involved with gut microbiota, while the underlying mechanism is unclear. Here, we investigated the role of inulin, a gut microbiota regulator, in the alleviation of PCOS. Our findings showed that inulin treatment significantly improved hyperandrogenism and glucolipid metabolism in both PCOS cohort and mice. Consistent with the cohort, inulin increased the abundance of microbial co-abundance group (CAG) 12 in PCOS mice, including Bifidobacterium species and other short-chain fatty acids (SCFAs)-producers. We further verified the enhancement of SCFAs biosynthesis capacity and fecal SCFAs content by inulin. Moreover, inulin decreased lipopolysaccharide-binding protein (LBP) and ameliorated ovarian inflammation in PCOS mice, whereas intraperitoneal lipopolysaccharide (LPS) administration reversed the protective effects of inulin. Furthermore, fecal microbiota transplantation (FMT) from inulin-treated patients with PCOS enhanced insulin sensitivity, improved lipid accumulation and thermogenesis, reduced hyperandrogenism and ovarian inflammatory response in antibiotic-treated mice. Collectively, these findings revealed that gut microbiota mediates the beneficial effects of inulin on metabolic disorder and ovarian dysfunction in PCOS. Therefore, modulating gut microbiota represents a promising therapeutic strategy for PCOS.}, }
@article {pmid40191185, year = {2025}, author = {Chen, L and Ruan, G and Zhao, X and Yi, A and Xiao, Z and Tian, Y and Cheng, Y and Chen, D and Wei, Y}, title = {Pseudomonas aeruginosa enhances anti-PD-1 efficacy in colorectal cancer by activating cytotoxic CD8[+] T cells.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1553757}, pmid = {40191185}, issn = {1664-3224}, mesh = {Animals ; *Colorectal Neoplasms/immunology/therapy/microbiology ; *Pseudomonas aeruginosa/immunology ; Mice ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Gastrointestinal Microbiome/immunology ; Humans ; *CD8-Positive T-Lymphocytes/immunology ; Fecal Microbiota Transplantation ; Female ; Lymphocyte Activation/immunology ; *T-Lymphocytes, Cytotoxic/immunology ; Cell Line, Tumor ; Male ; }, abstract = {BACKGROUND: Immune checkpoint therapy for colorectal cancer (CRC) has been found to be unsatisfactory for clinical treatment. Fecal microbiota transplantation (FMT) has been shown to remodel the intestinal flora, which may improve the therapeutic effect of αPD-1. Further exploration of key genera that can sensitize cells to αPD-1 for CRC treatment and preliminary exploration of immunological mechanisms may provide effective guidance for the clinical treatment of CRC.<br><br>METHODS: In this study, 16S rRNA gene sequencing was analyzed in the fecal flora of both responders and no-responders to &#x3b1;PD-1 treatment, and the therapeutic effect was experimentally verified.<br><br>RESULTS: Pseudomonas aeruginosa was found to be highly abundant in the fecal flora of treated mice, and Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) in combination with &#x3b1;PD-1 was effective in the treatment of CRC through the induction of CD8[+] T-cell immunological effects.<br><br>CONCLUSION: The clinical drug PA-MSHA can be used in combination with &#x3b1;PD-1 for the treatment of CRC as a potential clinical therapeutic option.}, }
@article {pmid40190259, year = {2025}, author = {Nagayama, M and Gogokhia, L and Longman, RS}, title = {Precision microbiota therapy for IBD: premise and promise.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2489067}, pmid = {40190259}, issn = {1949-0984}, support = {R01 AT013241/AT/NCCIH NIH HHS/United States ; R01 DK128257/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; *Inflammatory Bowel Diseases/therapy/microbiology ; Animals ; *Precision Medicine/methods ; }, abstract = {Inflammatory Bowel Disease (IBD) is a spectrum of chronic inflammatory diseases of the intestine that includes subtypes of ulcerative colitis (UC) and Crohn's Disease (CD) and currently has no cure. While IBD results from a complex interplay between genetic, environmental, and immunological factors, sequencing advances over the last 10-15 years revealed signature changes in gut microbiota that contribute to the pathogenesis of IBD. These findings highlight IBD as a disease target for microbiome-based therapies, with the potential to treat the underlying microbial pathogenesis and provide adjuvant therapy to the emerging spectrum of advanced therapies for IBD. Building on the success of fecal microbiota transplantation (FMT) for Clostridioides difficile infection, therapies targeting gut microbiota have emerged as promising approaches for treating IBD; however, unique aspects of IBD pathogenesis highlight the need for more precision in the approach to microbiome therapeutics that leverage aspects of recipient and donor selection, diet and xenobiotics, and strain-specific interactions to enhance the efficacy and safety of IBD therapy. This review focuses on both pre-clinical and clinical studies that support the premise for microbial therapeutics for IBD and aims to provide a framework for the development of precision microbiome therapeutics to optimize clinical outcomes for patients with IBD.}, }
@article {pmid40189556, year = {2025}, author = {Zhang, Y and Si, L and Shu, X and Qiu, C and Wan, X and Li, H and Ma, S and Jin, X and Wei, Z and Hu, H}, title = {Gut microbiota contributes to protection against porcine deltacoronavirus infection in piglets by modulating intestinal barrier and microbiome.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {93}, pmid = {40189556}, issn = {2049-2618}, mesh = {Animals ; Swine ; *Gastrointestinal Microbiome ; *Deltacoronavirus/physiology ; *Swine Diseases/microbiology/virology/prevention &amp; control ; *Coronavirus Infections/veterinary/microbiology/virology ; Fecal Microbiota Transplantation ; *Intestinal Mucosa/microbiology ; Feces/microbiology ; Diarrhea ; Intestines/microbiology/virology ; }, abstract = {BACKGROUND: Gut microbiota plays a critical role in counteracting enteric viral infection. Our previous study demonstrated that infection of porcine deltacoronavirus (PDCoV) disturbs gut microbiota and causes intestinal damage and inflammation in piglets. However, the influence of gut microbiota on PDCoV infection remains unclear.<br><br>RESULTS: Firstly, the relationship between gut microbiota and disease severity of PDCoV infection was evaluated using 8-day-old and 90-day-old pigs. The composition of gut microbiota was significantly altered in 8-day-old piglets after PDCoV infection, leading to severe diarrhea and intestinal damage. In contrast, PDCoV infection barely affected the 90-day-old pigs. Moreover, the diversity (richness and evenness) of microbiota in 90-day-old pigs was much higher compared to the 8-day-old piglets, suggesting the gut microbiota is possibly associated with the severity of PDCoV infection. Subsequently, transplanting the fecal microbiota from the 90-day-old pigs to the 3-day-old piglets alleviated clinical signs of PDCoV infection, modulated the diversity and composition of gut microbiota, and maintained the physical and chemical barrier of intestines. Additionally, metabolomic analysis revealed that the fecal microbiota transplantation (FMT) treatment upregulated the swine intestinal arginine biosynthesis, FMT significantly inhibited the inflammatory response in piglet intestine by modulating the TLR4/MyD88/NF-&#x3ba;B signaling pathway.<br><br>CONCLUSIONS: PDCoV infection altered the structure and composition of the gut microbiota in neonatal pigs. FMT treatment mitigated the clinical signs of PDCoV infection in the piglets by modulating the gut microbiota composition and intestinal barrier, downregulating the inflammatory response. The preventive effect of FMT provides novel targets for the development of therapeutics against enteropathogenic coronaviruses. Video Abstract.}, }
@article {pmid40189555, year = {2025}, author = {Zhou, J and Lu, P and He, H and Zhang, R and Yang, D and Liu, Q and Liu, Q and Liu, M and Zhang, G}, title = {The metabolites of gut microbiota: their role in ferroptosis in inflammatory bowel disease.}, journal = {European journal of medical research}, volume = {30}, number = {1}, pages = {248}, pmid = {40189555}, issn = {2047-783X}, support = {No.82474662//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Ferroptosis ; *Gastrointestinal Microbiome/physiology ; *Inflammatory Bowel Diseases/microbiology/metabolism/therapy/pathology ; Oxidative Stress ; Animals ; Fatty Acids, Volatile/metabolism ; Bile Acids and Salts/metabolism ; }, abstract = {Inflammatory bowel disease (IBD) includes chronic inflammatory conditions, such as Crohn's disease and ulcerative colitis, characterized by impaired function of the intestinal mucosal epithelial barrier. In recent years, ferroptosis, a novel form of cell death, has been confirmed to be involved in the pathological process of IBD and is related to various pathological changes, such as oxidative stress and inflammation. Recent studies have further revealed the complex interactions between the microbiome and ferroptosis, indicating that ferroptosis is an important target for the regulation of IBD by the gut microbiota and its metabolites. This article reviews the significant roles of gut microbial metabolites, such as short-chain fatty acids, tryptophan, and bile acids, in ferroptosis in IBD. These metabolites participate in the regulation of ferroptosis by influencing the intestinal microenvironment, modulating immune responses, and altering oxidative stress levels, thereby exerting an impact on the pathological development of IBD. Treatments based on the gut microbiota for IBD are gradually becoming a research hotspot. Finally, we discuss the potential of current therapeutic approaches, including antibiotics, probiotics, prebiotics, and fecal microbiota transplantation, in modulating the gut microbiota, affecting ferroptosis, and improving IBD symptoms. With a deeper understanding of the interaction mechanisms between the gut microbiota and ferroptosis, it is expected that more precise and effective treatment strategies for IBD will be developed in the future.}, }
@article {pmid40189523, year = {2025}, author = {Yu, X and Chen, Y and Lei, L and Li, P and Lin, D and Shen, Y and Hou, C and Chen, J and Fan, Y and Jin, Y and Lu, H and Wu, D and Xu, Y}, title = {Mendelian randomization analysis of blood metabolites and immune cell mediators in relation to GVHD and relapse.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {201}, pmid = {40189523}, issn = {1741-7015}, support = {QNXM2024010//Suzhou Science and Education Strengthening Health Youth ProjectSuzhou Science and Education Strengthening Health Youth Project/ ; MQ2024022//Medical research project of Jiangsu Provincial Health Commission/ ; BXQN2023032//Boxi cultivation program project of the First Affiliated Hospital of Suzhou University/ ; KYCX23_3270//Postgraduate Research &amp; Practice Innovation Program of Jiangsu Province/ ; SKJY2021049//Suzhou Science and Technology Program Project/ ; SKY2022043//Suzhou Science and Technology Program Project/ ; SLT201911//Suzhou Science and Technology Program Project/ ; 82100231//National Natural Science Foundation of China/ ; 82020108003//National Natural Science Foundation of China/ ; 82070187//National Natural Science Foundation of China/ ; CXZX202201//Jiangsu Provincial Medical Innovation Center/ ; 2022YFC2502700//National Key Research and Development Program/ ; }, mesh = {*Graft vs Host Disease/genetics/blood/immunology ; Humans ; *Mendelian Randomization Analysis ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Recurrence ; Genome-Wide Association Study ; Male ; Female ; }, abstract = {BACKGROUND: Graft-versus-host disease (GVHD) and relapse are major complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Metabolites play crucial roles in immune regulation, but their causal relationships with GVHD and relapse remain unclear.<br><br>METHODS: We utilized genetic variants from genome-wide association studies (GWAS) of 309 known metabolites as instrumental variables to evaluate their causal effects on acute GVHD (aGVHD), gut GVHD, chronic GVHD (cGVHD), and relapse in different populations. Multiple causal inference methods, heterogeneity assessments, and pleiotropy tests were conducted to ensure result robustness. Multivariable MR analysis was performed to adjust for potential confounders, and validation MR analysis further confirmed key findings. Mediation MR analysis was employed to explore indirect causal pathways.<br><br>RESULTS: After correction for multiple testing, we identified elevated pyridoxate and proline levels as protective factors against grade 3-4 aGVHD (aGVHD3) and relapse, respectively. Conversely, glycochenodeoxycholate increased the risk of aGVHD3, whereas 1-stearoylglycerophosphoethanolamine had a protective effect. The robustness and stability of these findings were confirmed by multiple causal inference approaches, heterogeneity, and horizontal pleiotropy analyses. Multivariable MR analysis further excluded potential confounding pleiotropic effects. Validation MR analyses supported the causal roles of pyridoxate and 1-stearoylglycerophosphoethanolamine, while mediation MR revealed that pyridoxate influences GVHD directly and indirectly via CD39[&#x2009;+]&#x2009;Tregs. Pathway analyses highlighted critical biochemical alterations, including disruptions in bile acid metabolism and the regulatory roles of vitamin B6 derivatives. Finally, clinical metabolic analyses, including direct fecal metabolite measurements, confirmed the protective role of pyridoxate against aGVHD.<br><br>CONCLUSIONS: Our findings provide novel insights into the metabolic mechanisms underlying GVHD and relapse after allo-HSCT. Identified metabolites, particularly pyridoxate, may serve as potential therapeutic targets for GVHD prevention and management.}, }
@article {pmid40189067, year = {2025}, author = {Jiang, ST and Wang, MQ and Gao, L and Zhang, QC and Tang, C and Dong, YF}, title = {Adjusting the composition of gut microbiota prevents the development of post-stroke depression by regulating the gut-brain axis in mice.}, journal = {Journal of affective disorders}, volume = {381}, number = {}, pages = {242-259}, doi = {10.1016/j.jad.2025.03.195}, pmid = {40189067}, issn = {1573-2517}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; Male ; *Fecal Microbiota Transplantation ; *Depression/prevention &amp; control/etiology/microbiology ; *Brain/metabolism ; *Stroke/complications/psychology ; Disease Models, Animal ; *Brain-Gut Axis/physiology/drug effects ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Fluoxetine/pharmacology ; Mice, Inbred C57BL ; }, abstract = {Disturbances in gut microbiota contribute to an imbalanced gut-brain axis, which is critical for post-stroke depression (PSD), while the underlying mechanisms remain unclear. The objective of this study was to examine the effects of modifying gut microbiota through antibiotic treatment (ABX) and fecal microbiota transplantation (FMT) on the progression of PSD. The PSD model was established by occluding the middle cerebral artery (MCAO), followed by a four-week isolated housing and restraint stress initiated three days after MCAO. For ABX, the PSD mice received antibiotic water for four weeks. While another group of PSD mice underwent FMT or fluoxetine (FLX) for four weeks. At day 35 post-MCAO, behavioral tests were conducted. Results indicated ABX and FMT significantly altered the composition of intestinal flora caused by PSD, all the treatments markedly attenuated anxiety- and depressive-like behaviors and inflammation in the gut and brain. ABX obviously alleviated PSD-induced disorder of intestinal barrier, decreased mRNA levels of TNF-α, IL-1β and IL-6, and decreased CD4[+] cells in the colon. While FMT significantly decreased CD8[+] cells and increased the goblet cells in colon. Furthermore, both ABX and FMT could reduce activated microglia and pro-inflammatory cytokines in the brain, alleviate decreased Nissl's bodies in the hippocampus, and reverse the decreases in 5-HT, Glu and DA in the striatum caused by PSD. Unlike ABX, FMT was similar to FLX. These findings suggest homeostasis of gut microbiota is indispensable for the development of PSD; adjusting the gut microbiota significantly improves PSD with enhanced functions of gut-brain axis.}, }
@article {pmid40188410, year = {2025}, author = {Oyovwi, MO and Ben-Azu, B and Babawale, KH}, title = {Therapeutic potential of microbiome modulation in reproductive cancers.}, journal = {Medical oncology (Northwood, London, England)}, volume = {42}, number = {5}, pages = {152}, pmid = {40188410}, issn = {1559-131X}, mesh = {Humans ; *Microbiota ; Probiotics/therapeutic use ; Female ; Dysbiosis/microbiology/therapy ; *Genital Neoplasms, Female/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Animals ; Gastrointestinal Microbiome ; }, abstract = {The human microbiome, a complex ecosystem of microbial communities, plays a crucial role in physiological processes, and emerging research indicates a potential link between it and reproductive cancers. This connection highlights the significance of understanding the microbiome's influence on cancer development and treatment. A comprehensive review of current literature was conducted, focusing on studies that investigate the relationship between microbiome composition, reproductive cancer progression, and potential therapeutic approaches to modulate the microbiome. Evidence suggests that imbalances in the microbiome, known as dysbiosis, may contribute to the development and progression of reproductive cancers. Specific microbial populations have been associated with inflammatory responses, immune modulation, and even resistance to conventional therapies. Interventions such as probiotics, dietary modifications, and fecal microbiota transplantation have shown promise in restoring healthy microbiome function and improving cancer outcomes in pre-clinical models, with pilot studies in humans indicating potential benefits. This review explores the therapeutic potential of microbiome modulation in the management of reproductive cancers, discussing the mechanisms involved and the evidence supporting microbiome-targeted therapies. Future research is warranted to unravel the complex interactions between the microbiome and reproductive cancer pathophysiology, paving the way for innovative approaches.}, }
@article {pmid40187666, year = {2025}, author = {Moreno-Sabater, A and Sintes, R and Truong, S and Lemoine, K and Camou, O and Kapel, N and Magne, D and Joly, AC and Quelven-Bertin, I and Alric, L and Hennequin, C and Sokol, H and , }, title = {Assessment of Dientamoeba fragilis interhuman transmission by fecal microbiota transplantation.}, journal = {International journal of antimicrobial agents}, volume = {66}, number = {2}, pages = {107504}, doi = {10.1016/j.ijantimicag.2025.107504}, pmid = {40187666}, issn = {1872-7913}, abstract = {Fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) requires careful selection of stool donors to avoid transmitting pathogens. Dientamoeba fragilis detection remains an exclusion criterion based on its uncertain pathogenicity. The aim of this study was to assess D. fragilis interhuman transmission by FMT and its impact on the clinical success of rCDI. A retrospective study was conducted in rCDI patients from the COSMIC cohort undergoing FMT to investigate the potential transfer of D. fragilis from donor to recipient. The impact of FMT involving D. fragilis was also evaluated in regard to the clinical outcomes of rCDI and adverse effects. This protist was found to be present in 15 of 86 healthy donors screened (18.7%) who voluntarily took part in an FMT program. Examination of D. fragilis presence in stool samples from 17 patients both before and after FMT with D. fragilis-positive donations revealed no evidence of interhuman transmission through this process. Analysis of clinical outcomes and adverse events in 124 rCDI patients who underwent FMT (with 45 receiving D. fragilis-positive donations) showed no significant differences in success rates between patients receiving positive or negative D. fragilis transplants (95.5% and 93.6%, respectively). No significant variances were observed in other side effects analyzed. These findings underscore the safety of using fecal transplant from D. fragilis-positive donors in the FMT process. D. fragilis should be removed from the donor screening, which will represent a major improvement in the donor selection process from financial and practical standpoints.}, }
@article {pmid40187461, year = {2025}, author = {Yang, J and Ren, H and Cao, J and Fu, J and Wang, J and Su, Z and Lu, S and Sheng, K and Wang, Y}, title = {Gut commensal Lachnospiraceae bacteria contribute to anti-colitis effects of Lactiplantibacillus plantarum exopolysaccharides.}, journal = {International journal of biological macromolecules}, volume = {309}, number = {Pt 1}, pages = {142815}, doi = {10.1016/j.ijbiomac.2025.142815}, pmid = {40187461}, issn = {1879-0003}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis/microbiology/drug therapy/pathology/metabolism/therapy ; Mice ; *Lactobacillus plantarum/chemistry ; *Probiotics/pharmacology ; *Polysaccharides, Bacterial/pharmacology ; Fecal Microbiota Transplantation ; *Clostridiales ; Mice, Inbred C57BL ; Male ; }, abstract = {The probiotic Lactiplantibacillus plantarum (L. plantarum) could ameliorate colitis. Alterations in the composition of gut microbiota (GM) have been proved in cases of colitis. The exopolysaccharides from L. plantarum HMPM2111 (LPE) could be effective in colitis through altering the composition of the GM. These effects were linked to inhibiting intestinal inflammation, regulating the TXNIP/NLRP3 inflammasome axis, and attenuating colonic barrier dysfunction. The combination of fecal microbiota transplantation (FMT) and antibiotic inducement showed that gut bacteria susceptible to vancomycin were inversely associated with colitis features and were necessary for the anti-inflammatory effects of LPE. The elevated abundances of gut commensal Lachnospiraceae bacteria were associated with the restoration of colitis treated by LPE. Metabolomics analysis showed that colitis mice treated with LPE had higher levels of propionate and tryptophan metabolites generated from gut bacteria. The administration of these metabolites protected colitis and resulted in a reduction in inflammatory responses. The outcomes of our investigation emerge the significance of the GM in controlling the protective implications of LPE against colitis. Lachnospiraceae bacteria, together with downstream metabolites, contribute substantially to protection. This work elucidates the essential function of the GM-metabolite axis in producing comprehensive protection versus colitis and identifies prospective treatment targets.}, }
@article {pmid40187430, year = {2025}, author = {Cai, M and Xue, SS and Zhou, CH and Feng, YC and Liu, JZ and Liu, R and Wang, P and Wang, HN and Peng, ZW}, title = {Effects of fecal microbiota transplantation from patients with generalized anxiety on anxiety-like behaviors: The role of the gut-microbiota-endocannabinoid-brain Axis.}, journal = {Journal of affective disorders}, volume = {381}, number = {}, pages = {131-149}, doi = {10.1016/j.jad.2025.04.018}, pmid = {40187430}, issn = {1573-2517}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Mice ; *Endocannabinoids/metabolism ; Male ; *Anxiety Disorders/therapy/microbiology/metabolism ; Humans ; *Brain/metabolism ; Amidohydrolases/metabolism/genetics ; Receptor, Cannabinoid, CB1/metabolism/genetics ; Mice, Knockout ; *Anxiety ; Mice, Inbred C57BL ; Monoacylglycerol Lipases/genetics/metabolism ; Disease Models, Animal ; Generalized Anxiety Disorder ; }, abstract = {BACKGROUND: Intestinal dysbacteriosis is frequently implicated in generalized anxiety disorder (GAD). However, the molecular mechanisms and functional changes of the gut-brain axis in GAD remain largely unexplored.<br><br>METHODS: We investigated anxiety-like behaviors, gut microbiota changes, brain region-specific endocannabinoid (eCB) system alterations, including the expression of cannabinoid type 1 (CB1R), monoacylglycerol lipase (MAGL), and fatty acid amide hydrolase (FAAH) in the hippocampus (Hip), prefrontal cortex (PFC), and amygdala (Amy), as well as plasma medium- and long-chain fatty acids (MLCFAs) in a mouse model of chronic restraint stress (CRS) and antibiotic-treated mice receiving fecal microbiota transplantation from GAD patients (FMT-GAD). Additionally, we assessed the impact of FMT-GAD on anxiety-like behavior in systemic CB1R/FAAH/MAGL knockout mice.<br><br>RESULTS: CRS induced anxiety-like behaviors, suppressed eCB signaling in the brain, and altered the gut microbiota and plasma MLCFA composition in mice. FMT-GAD-treated mice exhibited anxiety-like behaviors, increased FAAH expression in the Hip and Amy, and MAGL expression in the Hip, while reducing CB1R expression in the Hip. FMT-GAD was associated with decreased plasma polyunsaturated fatty acids (PUFAs) and reduced microbiome function for fatty acid biosynthesis. Notably, FMT-GAD intensified anxiety-like behaviors in CB1R-KO mice but failed to induce anxiety-like behaviors in MAGL-KO and FAAH-KO mice.<br><br>CONCLUSIONS: This study demonstrates that the interplay between the gut microbiota and the eCB system modulates GAD-related anxiety-like behaviors.}, }
@article {pmid40185558, year = {2025}, author = {Shin, JH and Jackson-Akers, JY and Hoang, SC and Behm, BW and Warren, CA}, title = {Fulminant Clostridioides difficile Infection: A Journey into the Unknown!.}, journal = {The Medical clinics of North America}, volume = {109}, number = {3}, pages = {721-734}, doi = {10.1016/j.mcna.2025.01.001}, pmid = {40185558}, issn = {1557-9859}, support = {R01 AI145322/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Clostridium Infections/diagnosis/therapy ; *Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/isolation &amp; purification ; Colectomy ; Fecal Microbiota Transplantation ; Ileostomy ; Immunoglobulins, Intravenous/therapeutic use ; }, abstract = {Clostridioides difficile is 1 of the 5 urgent antibiotic resistance threats in the United States as reported by the Centers for Disease Control and Prevention. Fulminant C difficile infection (CDI), characterized by hallmarks of critical illness such as hypotension, shock, or megacolon, has been difficult to define and treat. In this article, we describe the diagnostic criteria for fulminant CDI, clinical factors and inflammatory markers. We review the currently recommended treatment modalities including antibiotics and surgical interventions, colectomy, and diverting loop ileostomy. We also included treatment approaches that are still investigational such as intestinal microbiota transplant, tigecycline, and intravenous immunoglobulin.}, }
@article {pmid40185194, year = {2025}, author = {Docherty, J}, title = {Therapeutic potential of faecal microbiota transplantation for alcohol use disorder, a narrative synthesis.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {138}, number = {}, pages = {111354}, doi = {10.1016/j.pnpbp.2025.111354}, pmid = {40185194}, issn = {1878-4216}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome/physiology ; *Alcoholism/therapy ; Animals ; Brain-Gut Axis/physiology ; }, abstract = {BACKGROUND: Faecal microbiota transplantation is proposed as an alternative therapy to treat alcohol use disorder and has completed a Phase 1 clinical trial, with a Phase 2 clinical trial underway. Alcohol, a modifiable risk factor for noncommunicable diseases, resulted in approximately 3 million global deaths (5 %) in 2016 according to the World Health Organization.<br><br>AIMS: A narrative synthesis examines the effects of alcohol and faecal microbiota transplantation on gut microbiota and how gut microbiota impacts the gut-brain axis, leading to certain behavioural symptoms of alcohol use disorder. These behavioural symptoms are alcohol craving and relapse in humans; and preference for alcohol, anxiety and depression in rodents.<br><br>SEARCH METHODS AND RESULTS: Electronic databases PubMed, Embase, and Scopus were searched in January 2024 using the terms: faecal microbiota trans* AND alcohol AND microbio*. Ten studies out of 964 met the inclusion criteria of published primary studies with faecal microbiota transplantation as an intervention to study the gut-brain axis in alcohol use disorder.<br><br>RESULTS: The gut microbiota is altered in alcohol use disorder, which can be modified with faecal microbiota transplantation. Behavioural symptoms such as alcohol craving and relapse are associated with inflammation due to a loss of intestinal barrier function. Beneficial microbiota produce short-chain fatty acids that maintain intestinal barrier function and reduce inflammation. Studies also reported anxiety and depression-like behaviours, in addition to a preference for alcohol in alcohol-na&#xef;ve rodents after faecal microbiota transplantation from patients with alcohol use disorder.<br><br>CONCLUSIONS: Faecal microbiota transplantation may moderate the behavioural symptoms of alcohol use disorder by altering gut microbiota, affecting intestinal permeability and inflammation, however, specific gut microbiota composition and long-term treatment outcomes require further clinical studies.}, }
@article {pmid40185172, year = {2025}, author = {Liu, C and Fan, P and Dai, J and Ding, Z and Yi, Y and Zhan, X and Wang, CC and Liang, R}, title = {Integrated microbiome and metabolome analysis reveals that Zishen Qingre Lishi Huayu recipe regulates gut microbiota and butyrate metabolism to ameliorate polycystic ovary syndrome.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {107533}, doi = {10.1016/j.micpath.2025.107533}, pmid = {40185172}, issn = {1096-1208}, abstract = {BACKGROUND: s: Polycystic ovary syndrome (PCOS) is a metabolic disorder disease strongly associated with gut microbiota (GM). Zishen Qingre Lishi Huayu recipe (ZQLHR), a traditional Chinese medicinal compound, has patented and shown therapeutic effects in treating PCOS in clinical trials without clear pharmacological mechanisms. This study aimed to disclose the potential therapeutic mechanism of ZQLHR on PCOS.<br><br>METHODS: We firstly confirmed the therapeutic effects of ZQLHR treatment in PCOS patients. 16S rRNA sequencing, untargeted metabolomics, fecal microbiota transplantation (FMT), high performance liquid chromatography (HPLC) and Person's correlation analysis were conducted to elucidate the potential therapeutic mechanism.<br><br>RESULTS: These results showed that PCOS symptoms in ZQLHR patients were significantly ameliorated. ZQLHR could increase the levels of butyrate-producing Lachnospira and Faecalibacterium and decrease the abundance of Escherichia-Shigella. Untargeted metabolomics showed that ZQLHR significantly improved host metabolic function, particularly butyrate metabolism and citrate cycle (TCA cycle) metabolism. The combined Faecalibacterium and butyrate metabolism datasets were correlated. Stool samples from ZQLHR patients could ameliorate ovarian architecture, significantly reduce testosterone (T), estradiol (E2) and luteinizing hormone (LH) levels and increased follicle-stimulating hormone (FSH) levels and increase the content of butyric acid in PCOS mice (P&#x2009;<&#x2009;0.01). Moreover, the correlation analysis showed that some biochemical parameters (T, E2, LH levels and FSH) and butyric acid were correlated.<br><br>CONCLUSION: We firstly depicted that ZQLHR could alleviate the series of symptom in women with PCOS by regulating gut microbiota and butyrate metabolism. This study provides a scientific basis and new ideas for the therapy of PCOS.}, }
@article {pmid40184763, year = {2025}, author = {Huang, M and Zhang, Y and Chen, Z and Yu, X and Luo, S and Peng, X and Li, X}, title = {Gut microbiota reshapes the TNBC immune microenvironment: Emerging immunotherapeutic strategies.}, journal = {Pharmacological research}, volume = {215}, number = {}, pages = {107726}, doi = {10.1016/j.phrs.2025.107726}, pmid = {40184763}, issn = {1096-1186}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Tumor Microenvironment/immunology ; Animals ; *Immunotherapy/methods ; *Triple Negative Breast Neoplasms/immunology/therapy/microbiology ; Female ; Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; }, abstract = {Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and poor prognosis. The gut microbiota, a diverse community of microorganisms in the gastrointestinal tract, plays a crucial role in regulating immune responses through the gut-immune axis. Recent studies have highlighted its significant impact on TNBC progression and the efficacy of immunotherapies. This review examines the interactions between gut microbiota and the immune system in TNBC, focusing on key immune cells and pathways involved in tumor immunity. It also explores microbiota modulation strategies, including probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation, as potential methods to enhance immunotherapeutic outcomes. Understanding these mechanisms offers promising avenues for improving treatment efficacy and patient prognosis in TNBC.}, }
@article {pmid40184501, year = {2025}, author = {de Schrijver, S and Vanhulle, E and Ingenbleek, A and Alexakis, L and Johannesen, CK and Broberg, EK and Harvala, H and Fischer, TK and Benschop, KSM and , }, title = {Epidemiological and clinical insights into enterovirus circulation in Europe, 2018 - 2023: a multi-center retrospective surveillance study.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiaf179}, pmid = {40184501}, issn = {1537-6613}, abstract = {BACKGROUND: Enteroviruses (EV) cause yearly outbreaks with severe infections, particularly in young children. This study investigates EV circulation, age-distribution, and clinical presentations in Europe from 2018-2023.<br><br>METHODS: Aggregated data were requested from ECDC National Focal Points for Surveillance and European Non-Polio Enterovirus Network. Data included detection month, specimen type, age-group, and clinical presentation for the ten most commonly reported EV types per year.<br><br>FINDINGS: Twenty-eight institutions from 16 countries reported 563,654 EV-tests during the study-period with 33,265 (5.9%) EV-positive. Forty-two types were identified (n=11,605 cases) with echovirus (E)30, coxsackievirus (CV)A6, EV-D68, E9, E11, CVB5, E18, CVB4, EV-A71, and E6 most frequently reported. E30 detection declined after 2018/2019, while CVA6, CVB5, E9, E11, and EV-D68 were prevalent both before and after the COVID-19 pandemic, and CVB4 and E18 were prevalent after the pandemic. Over the study period, a shift in seasons (summer to fall) and specimen positivity (feces to respiratory) was observed. Neurological signs predominated among EV-A71, CVB4, CVB5, E6, E9, E11, E18, and E30 (30-72%). CVB4, CVB5, E9, E11, and E18 were also frequently reported among neonates (18-32%). CVA6 was frequently associated with HFMD, and EV-D68 with respiratory infections. Paralysis was reported among 22 infections, associated with ten non-polio types.<br><br>CONCLUSION: This study emphasizes the widespread circulation and severe nature of EV infections in Europe, particularly among neonates, as well as the (re-)emergence of specific types post-pandemic. Our findings highlight the need for continuous EV-surveillance to monitor variation in circulation, age, and clinical presentations, including paralysis among non-polio EV infections.}, }
@article {pmid40183701, year = {2025}, author = {Peng, W and Jin, Z and Liu, J and Zhang, Q and Liu, W}, title = {Tangeretin modulates gut microbiota metabolism and macrophage immunity following fecal microbiota transplantation in obesity.}, journal = {Journal of food science}, volume = {90}, number = {4}, pages = {e70171}, doi = {10.1111/1750-3841.70171}, pmid = {40183701}, issn = {1750-3841}, support = {//National Natural Science Foundation of China (81670481)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Obesity/therapy/immunology/microbiology/metabolism/drug therapy ; Male ; Mice, Inbred C57BL ; Mice ; *Fecal Microbiota Transplantation ; *Macrophages/immunology/drug effects ; *Flavones/pharmacology ; Diet, High-Fat/adverse effects ; Adipose Tissue/metabolism ; }, abstract = {Obesity, characterized by excessive body fat, is a leading preventable cause of death globally and represents one of the most critical public health challenges of the 21st century. This study aimed to investigate the action of tangeretin on gut microbiota metabolism and inflammation in high-fat diet (HFD)-induced obese mice. A model of obesity was established using 6-week-old male C57BL/6J mice fed with HFD, which were then used for the treatment with tangeretin (20 mg/kg/mice/day) or antibiotic (Abx). The results showed that the tangeretin intervention alleviated fat deposition and disorder of cellular structural integrity in the model group. The obese mice showed a significant increase in the levels of lipid (glycerol, triglyceride, and total cholesterol), inflammatory factors (IL-6 and TNF-α), and F4/80 expression in both serum and adipose tissues. Following tangeretin treatment, the levels of lipid, inflammatory factors, and the ratio of F4/80 + CD206 + macrophages were decreased in both serum and adipose tissue. 16S rRNA sequencing and LC-MS/MS analysis revealed that tangeretin decreased obesity in HFD-induced obese mice by interacting with gut microbiota, particularly influencing Parabacteroides, Blautia, and Parasutterella, and amino acids such as threonine, isoleucine, leucine, phenylalanine, arginine, glutamine, L-tryptophan, and tyrosine. Abx-mediated clearance of gut microbiota blocked the HFD-induced obesity and abrogated the therapeutic effects of tangeretin in obese mice. Fecal microbiota transplantation (FMT) proved that clearing gut microbiota with Abx blocked the beneficial effects of FMT[HFD+Tangeretin] intervention. These findings suggested that tangeretin improved HFD-induced obesity by regulating lipid metabolism and modulating F4/80 macrophage activation via gut microbiota.}, }
@article {pmid40182777, year = {2025}, author = {Zhou, S and Zhou, X and Zhang, P and Zhang, W and Huang, J and Jia, X and He, X and Sun, X and Su, H}, title = {The gut microbiota-inflammation-HFpEF axis: deciphering the role of gut microbiota dysregulation in the pathogenesis and management of HFpEF.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1537576}, pmid = {40182777}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Heart Failure/microbiology/therapy/physiopathology/etiology ; *Inflammation/microbiology ; *Dysbiosis ; Animals ; Stroke Volume ; }, abstract = {Heart failure with preserved left ventricular ejection fraction (HFpEF) is a disease that affects multiple organs throughout the body, accounting for over 50% of heart failure cases. HFpEF has a significant impact on individuals' life expectancy and quality of life, but the exact pathogenesis remains unclear. Emerging evidence implicates low-grade systemic inflammation as a crucial role in the onset and progression of HFpEF. Gut microbiota dysregulation and associated metabolites alteration, including short-chain fatty acids, trimethylamine N-oxides, amino acids, and bile acids can exacerbate chronic systemic inflammatory responses and potentially contribute to HFpEF. In light of these findings, we propose the hypothesis of a "gut microbiota-inflammation-HFpEF axis", positing that the interplay within this axis could be a crucial factor in the development and progression of HFpEF. This review focuses on the role of gut microbiota dysregulation-induced inflammation in HFpEF's etiology. It explores the potential mechanisms linking dysregulation of the gut microbiota to cardiac dysfunction and evaluates the therapeutic potential of restoring gut microbiota balance in mitigating HFpEF severity. The objective is to offer novel insights and strategies for the management of HFpEF.}, }
@article {pmid40182189, year = {2025}, author = {Burdette, RA and Whitt, CC and Behm, BW and Warren, CA}, title = {Avoiding Premature Antibiotic Use in Recurrent Clostridioides difficile Infection After Fecal Microbiota Transplant.}, journal = {ACG case reports journal}, volume = {12}, number = {4}, pages = {e01660}, pmid = {40182189}, issn = {2326-3253}, abstract = {Recurrent Clostridioides difficile infection (rCDI) remains a major clinical challenge, often requiring fecal microbiota transplantation (FMT) after conventional treatment fails. An 86-year-old woman with rCDI underwent FMT after failing multiple antibiotic therapies. Shortly after FMT, she experienced diarrhea and abdominal pain, alongside positive C. difficile stool tests. Antibiotics were withheld because of clinical improvement, and she achieved complete resolution of symptoms without further treatment. This case demonstrates the potential benefit of withholding antibiotics in rCDI patients soon after FMT to allow sufficient time for donor microbiota engraftment and underscores the need for further research to optimize post-FMT management.}, }
@article {pmid40180421, year = {2025}, author = {Clavijo-Salomon, MA and Trinchieri, G}, title = {Unlocking the power of the microbiome for successful cancer immunotherapy.}, journal = {Journal for immunotherapy of cancer}, volume = {13}, number = {4}, pages = {}, pmid = {40180421}, issn = {2051-1426}, mesh = {Humans ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation/methods ; *Microbiota ; }, abstract = {In recent years, evidence has shown that the gut microbiome significantly influences responses to immunotherapy. This has sparked interest in targeting it to improve therapy outcomes and predictions of response and toxicity. Research has demonstrated that dysbiosis, often resulting from antibiotic use, can diminish the effectiveness of immune checkpoint inhibitors, and this lack of efficacy could be linked to systemic inflammation. Certain bacterial species have been identified as having beneficial and harmful effects on immunotherapy in the clinic. While a clear consensus has yet to emerge on the optimal species for therapeutic use, introducing a new microbiome into immunotherapy-refractory patients may boost their chances of responding to further treatment attempts. State-of-the-art interventions targeting the microbiome-such as fecal microbiota transplantation-are being assessed clinically for their safety and potential to enhance treatment outcomes, with promising results. Additionally, the microbiome has been leveraged for its power to predict clinical outcomes using machine learning, and surprisingly, its predictive capability is comparable to that of other described multi-biomarker clinical scores. Here, we discuss developing knowledge concerning the microbiome's significance in cancer immunotherapy and outline future strategies for maximizing its potential in immuno-oncology.}, }
@article {pmid40177494, year = {2025}, author = {Liu, J and Li, F and Yang, L and Luo, S and Deng, Y}, title = {Gut microbiota and its metabolites regulate insulin resistance: traditional Chinese medicine insights for T2DM.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1554189}, pmid = {40177494}, issn = {1664-302X}, abstract = {The gut microbiota is closely associated with the onset and development of type 2 diabetes mellitus (T2DM), characterized by insulin resistance (IR) and chronic low-grade inflammation. However, despite the widespread use of first-line antidiabetic drugs, IR in diabetes and its complications continue to rise. The gut microbiota and its metabolic products may promote the development of T2DM by exacerbating IR. Therefore, regulating the gut microbiota has become a promising therapeutic strategy, with particular attention given to probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. This review first examines the relationship between gut microbiota and IR in T2DM, summarizing the research progress of microbiota-based therapies in modulating IR. We then delve into how gut microbiota-related metabolic products contribute to IR. Finally, we summarize the research findings on the role of traditional Chinese medicine in regulating the gut microbiota and its metabolic products to improve IR. In conclusion, the gut microbiota and its metabolic products play a crucial role in the pathophysiological process of T2DM by modulating IR, offering new insights into potential therapeutic strategies for T2DM.}, }
@article {pmid40177417, year = {2025}, author = {Wu, Y and Chen, X and Wu, Q and Wang, Q}, title = {Research progress on fecal microbiota transplantation in tumor prevention and treatment.}, journal = {Open life sciences}, volume = {20}, number = {1}, pages = {20220954}, pmid = {40177417}, issn = {2391-5412}, abstract = {The application of fecal microbiota transplantation (FMT) as a therapeutic strategy to directly modify the makeup of the gut microbiota has made significant progress in the last few decades. The gut microbiota, a sizable microbial community present in the human gut, is essential for digestion, immunomodulation, and nutrition absorption. Alternatively, a growing body of research indicates that gut microbiota is a key contributor to cancer, and intratumoral bacteria are considered to be crucial "accomplices" in the development and metastasis of malignancies. The exceptional clinical effectiveness of FMT in treating melanoma patients has been adequately established in earlier research, which has created new avenues for the diagnosis and treatment of cancer and sparked an increasing interest in the treatment and prevention of other cancers. However, further research on the function and mechanisms of the gut microbiota is required to properly comprehend the impact and role of these organisms in tumor regulation. In this article, we present a detailed account of the influence of FMT on the entire course of cancer patients' illness and treatment, from tumor development, metastasis, and invasion, to the impact and application of treatment and prognosis, as well as address the associated mechanisms.}, }
@article {pmid40176987, year = {2025}, author = {Yarahmadi, A and Najafiyan, H and Yousefi, MH and Khosravi, E and Shabani, E and Afkhami, H and Aghaei, SS}, title = {Beyond antibiotics: exploring multifaceted approaches to combat bacterial resistance in the modern era: a comprehensive review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1493915}, pmid = {40176987}, issn = {2235-2988}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use/pharmacology ; *Drug Resistance, Bacterial ; *Bacterial Infections/therapy/microbiology/drug therapy ; Animals ; *Bacteria/drug effects ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Antimicrobial Peptides/therapeutic use ; }, abstract = {Antibiotics represent one of the most significant medical breakthroughs of the twentieth century, playing a critical role in combating bacterial infections. However, the rapid emergence of antibiotic resistance has become a major global health crisis, significantly complicating treatment protocols. This paper provides a narrative review of the current state of antibiotic resistance, synthesizing findings from primary research and comprehensive review articles to examine the various mechanisms bacteria employ to counteract antibiotics. One of the primary sources of antibiotic resistance is the improper use of antibiotics in the livestock industry. The emergence of drug-resistant microorganisms from human activities and industrial livestock production has presented significant environmental and public health concerns. Today, resistant nosocomial infections occur following long-term hospitalization of patients, causing the death of many people, so there is an urgent need for alternative treatments. In response to this crisis, non-antibiotic therapeutic strategies have been proposed, including bacteriophages, probiotics, postbiotics, synbiotics, fecal microbiota transplantation (FMT), nanoparticles (NPs), antimicrobial peptides (AMPs), antibodies, traditional medicines, and the toxin-antitoxin (TA) system. While these approaches offer innovative solutions for addressing bacterial infections and preserving the efficacy of antimicrobial therapies, challenges such as safety, cost-effectiveness, regulatory hurdles, and large-scale implementation remain. This review examines the potential and limitations of these strategies, offering a balanced perspective on their role in managing bacterial infections and mitigating the broader impact of antibiotic resistance.}, }
@article {pmid40176137, year = {2025}, author = {Sommer, F and Bernardes, JP and Best, L and Sommer, N and Hamm, J and Messner, B and López-Agudelo, VA and Fazio, A and Marinos, G and Kadibalban, AS and Ito, G and Falk-Paulsen, M and Kaleta, C and Rosenstiel, P}, title = {Life-long microbiome rejuvenation improves intestinal barrier function and inflammaging in mice.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {91}, pmid = {40176137}, issn = {2049-2618}, support = {SO1141/10-1//Deutsche Forschungsgemeinschaft/ ; CRC1182//Deutsche Forschungsgemeinschaft/ ; miTARGET//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; RNA, Ribosomal, 16S/genetics ; *Fecal Microbiota Transplantation ; *Aging/physiology ; Feces/microbiology ; *Bacteria/classification/genetics/isolation &amp; purification ; Male ; *Intestinal Mucosa/microbiology/metabolism ; *Inflammation/microbiology ; Mice, Inbred C57BL ; *Rejuvenation ; Permeability ; *Intestines/microbiology ; Metagenomics ; Intestinal Barrier Function ; }, abstract = {BACKGROUND: Alterations in the composition and function of the intestinal microbiota have been observed in organismal aging across a broad spectrum of animal phyla. Recent findings, which have been derived mostly in simple animal models, have even established a causal relationship between age-related microbial shifts and lifespan, suggesting microbiota-directed interventions as a potential tool to decelerate aging processes. To test whether a life-long microbiome rejuvenation strategy could delay or even prevent aging in non-ruminant mammals, we performed recurrent fecal microbial transfer (FMT) in mice throughout life. Transfer material was either derived from 8-week-old mice (young microbiome, yMB) or from animals of the same age as the recipients (isochronic microbiome, iMB) as control. Motor coordination and strength were analyzed by rotarod and grip strength tests, intestinal barrier function by serum LAL assay, transcriptional responses by single-cell RNA sequencing, and fecal microbial community properties by 16S rRNA gene profiling and metagenomics.<br><br>RESULTS: Colonization with yMB improved coordination and intestinal permeability compared to iMB. yMB encoded fewer pro-inflammatory factors and altered metabolic pathways favoring oxidative phosphorylation. Ecological interactions among bacteria in yMB were more antagonistic than in iMB implying more stable microbiome communities. Single-cell RNA sequencing analysis of intestinal mucosa revealed a salient shift of cellular phenotypes in the yMB group with markedly increased ATP synthesis and mitochondrial pathways as well as a decrease of age-dependent mesenchymal hallmark transcripts in enterocytes and TA cells, but reduced inflammatory signaling in macrophages.<br><br>CONCLUSIONS: Taken together, we demonstrate that life-long and repeated transfer of microbiota material from young mice improved age-related processes including coordinative ability (rotarod), intestinal permeability, and both metabolic and inflammatory profiles mainly of macrophages but also of other immune cells. Video Abstract.}, }
@article {pmid40175647, year = {2025}, author = {Ahn, JS and Kim, S and Han, EJ and Hong, ST and Chung, HJ}, title = {Increasing spatial working memory in mice with Akkermansia muciniphila.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {546}, pmid = {40175647}, issn = {2399-3642}, support = {C512230//Korea Basic Science Institute (KBSI)/ ; RS-2023-00224099//National Research Foundation of Korea (NRF)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; *Memory, Short-Term/physiology ; Male ; *Spatial Memory/physiology ; Akkermansia ; Humans ; Verrucomicrobia ; Feces/microbiology ; Brain-Derived Neurotrophic Factor/metabolism ; }, abstract = {Recent research has shown the gut microbiome's impact on memory, yet limitations hinder the identification of specific microbes linked to cognitive function. We measured spatial working memory in individual mice before and after fecal microbiota transplantation (FMT) to develop a targeted analysis that identifies memory-associated strains while minimizing host genetic effects. Transplantation of human fecal into C57BL/6 mice yielded varied outcomes: some mice showed significant improvements while others had negligible changes, indicating that these changes are due to differences in FMT colonization. Metagenomic analysis, stratified by memory performance, revealed a positive correlation between the abundance of Akkermansia muciniphila and improved memory. Moreover, administering two A. muciniphila strains, GMB 0476 and GMB 2066, to wild-type mice elevated spatial working memory via BDNF activation. Our findings indicate that specific gut microbes, particularly A. muciniphila, may modulate memory and represent potential targets for therapeutic intervention in cognitive enhancement.}, }
@article {pmid40175389, year = {2025}, author = {Braga, JD and Yang, Y and Nagao, T and Kato, N and Yanaka, N and Nishio, K and Okada, M and Kuroda, M and Yamaguchi, S and Kumrungsee, T}, title = {Fructooligosaccharides and Aspergillus enzymes increase brain GABA and homocarnosine by modulating microbiota in adolescent mice.}, journal = {NPJ science of food}, volume = {9}, number = {1}, pages = {48}, pmid = {40175389}, issn = {2396-8370}, abstract = {Recent research suggests that dietary prebiotics, probiotics, or healthy fecal-microbiota transplantation attenuate gut microbiota dysbiosis and ameliorate neurological disorders, in which gut-microbiota-derived γ-aminobutyric acid (GABA) has gained much attention as one of key mediators in the gut-brain axis. Although it is widely accepted that prebiotics and probiotics induce gut and brain GABA production via modulating gut microbiota, only evidence of probiotics has been solidly demonstrated while this evidence of prebiotics is scarce. Here, we demonstrated that prebiotic fructo-oligosaccharides and Aspergillus-derived enzymes elevated gut and brain GABA concentrations by modulating gut microbiota. Interestingly, we found that the prebiotic and enzymes increased a brain-specific dipeptide, homocarnosine. Gut GABA levels were found correlated with brain GABA/homocarnosine levels. Parabateroides, Akkermansia, Muribaculum, Hungatella, Marvinbryantia, Flavonifractor, and Incertae_sedis exhibited a positive correlation with gut GABA and brain GABA/homocarnosine levels, while Blautia, Unclassified_Lachnospiraceae, Colidextribacter, Acetatifactor, Roseburia, Unclassified_Oscillospiraceae, Romboutsia, and Eubacterium_coprostanoligenes exhibited a negative correlation with those levels.}, }
@article {pmid40174272, year = {2025}, author = {Abavisani, M and Tafti, P and Khoshroo, N and Ebadpour, N and Khoshrou, A and Kesharwani, P and Sahebkar, A}, title = {The heart of the matter: How gut microbiota-targeted interventions influence cardiovascular diseases.}, journal = {Pathology, research and practice}, volume = {269}, number = {}, pages = {155931}, doi = {10.1016/j.prp.2025.155931}, pmid = {40174272}, issn = {1618-0631}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Cardiovascular Diseases/microbiology/therapy/prevention &amp; control ; *Dysbiosis/microbiology/complications ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics ; Animals ; }, abstract = {The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.}, }
@article {pmid40171188, year = {2025}, author = {Li, C and Cheng, D and Ren, H and Zhang, T}, title = {Unraveling the gut microbiota's role in PCOS: a new frontier in metabolic health.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1529703}, pmid = {40171188}, issn = {1664-2392}, mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; Female ; *Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Animals ; Prebiotics ; }, abstract = {Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting reproductive-age women, characterized primarily by hyperandrogenism, ovulatory dysfunction, and metabolic abnormalities. In recent years, the gut microbiota has garnered widespread attention for its potential role as a key regulator of host metabolism in the pathogenesis of PCOS. Studies have shown that PCOS patients exhibit dysbiosis in their gut microbiota, characterized by reduced microbial diversity, an imbalance in the ratio of Firmicutes to Bacteroidetes, changes in the abundance of specific taxa, and abnormal levels of metabolic products. These alterations may exacerbate metabolic dysfunction in PCOS through multiple mechanisms, including influencing host energy metabolism, disrupting lipid and bile acid metabolism, and inducing chronic inflammation. Addressing gut dysbiosis through the modulation of patients' microbiomes-such the use of, prebiotics, fecal microbiota transplantation, and optimizing diet lifestyle-may offer strategies for improving metabolic abnormalities and alleviating clinical symptoms in PCOS. Additionally, the gut microbiome promises as a potential marker, aiding in the precise diagnosis and personalization of PCOS. Although our current understanding of how the gut microbiota influences PCOS is still limited, research is needed to explore the causal relationships and mechanisms involved, providing a more reliable theoretical basis for clinical. This review aims summarize the research progress on the relationship between gut microbiota and PCOS, and to suggest future directions to promote the development of prevention and treatment strategies for PCOS.}, }
@article {pmid40171160, year = {2025}, author = {Chen, F and Zhang, H and Wei, Q and Tang, J and Yin, L and Ban, Y and Zhou, Q}, title = {Disrupted gut microbiota promotes the progression of chronic kidney disease in 5/6 nephrectomy mice by Bacillus pumilus gavage.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1548767}, pmid = {40171160}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Renal Insufficiency, Chronic/microbiology/metabolism ; Mice ; *Probiotics/administration &amp; dosage ; *Nephrectomy ; *Disease Models, Animal ; *RNA, Ribosomal, 16S/genetics ; *Disease Progression ; *Bacillus pumilus ; Feces/microbiology ; Kidney/pathology ; Male ; Dysbiosis/microbiology ; Bacteria/classification/isolation &amp; purification/genetics ; Mice, Inbred C57BL ; Metabolomics ; }, abstract = {BACKGROUND: Our previous study identified differences in the gut microbiota between patients with chronic kidney disease (CKD) and healthy individuals. We observed that antibiotic-treated mice exhibited symptoms similar to those of patients with CKD after receiving a gut microbiota transplant from patients with CKD. Bacillus pumilus (B. pumilus), an alien microorganism to both human and mouse gut microbiota, possesses antibiotic properties that can alter the microbial community structure. Therefore, this study aimed to explore how changes in the gut microbiota structure induced by the oral gavage of B. pumilus affect the progression of CKD. We sought to identify the gut microbes and metabolic pathways associated with CKD to lay the groundwork for future clinical probiotic applications in patients with CKD.<br><br>METHODS: We constructed sham-operated and 5/6 nephrectomy mice as the sham control (SC) and CKD models, respectively. CKD models were divided into a control group (CG) and an intervention group (IG). After 16 weeks of normal feeding, the IG were treated with B. pumilus by oral gavage, while SC and CG were treated with PBS once daily, 5 days per week, for 7 weeks. Fecal samples were collected for 16s rRNA sequencing and metabolomic analysis, kidneys were harvested for histological examination, and the colon was used for RT-PCR analysis.<br><br>RESULTS: B. pumilus intervention exacerbated gut microbial homeostasis in CKD mice and increased serum creatinine and urea nitrogen levels, further aggravating kidney damage. 16s rRNA and metabolomic analysis revealed that Parvibacter and Enterorhabdus were probiotics related to kidney function, while Odoribacter was associated with kidney injury. Metabolomic analysis showed that glycerophospholipid and lysine metabolism were upregulated in CKD model mice, correlating with kidney damage.<br><br>CONCLUSION: This study shows that changes in the gut microbiota can affect the kidneys through gut metabolism, confirming that the lack of probiotics and the proliferation of harmful bacteria leading to gut microbiota dysbiosis are drivers of CKD progression. Our findings provide a basis for clinical interventions using gut microbes and offer a reference for targeted probiotic therapy.}, }
@article {pmid40170570, year = {2025}, author = {Yao, N and Liu, Y and Zhang, ZY and Tian, M and Xie, WJ and Zhao, H and Yang, H and Rodewald, LE and Wen, N and Yin, ZD and Wang, FZ and Wang, Q and Xu, JW}, title = {Excretion and clearance of Sabin-like type 3 poliovirus in a child diagnosed with severe combined immunodeficiency.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {21}, number = {1}, pages = {2484882}, pmid = {40170570}, issn = {2164-554X}, mesh = {Humans ; *Severe Combined Immunodeficiency/complications ; *Poliovirus/genetics/immunology ; *Virus Shedding ; *Poliomyelitis ; *Feces/virology ; Infant ; Female ; Child, Preschool ; Pilot Projects ; Male ; Child ; Poliovirus Vaccine, Oral/adverse effects/immunology ; Homeodomain Proteins/genetics ; Hematopoietic Stem Cell Transplantation/adverse effects ; }, abstract = {Children with primary immunodeficiency disorder (PID) are at higher risk of developing vaccine-associated paralytic poliomyelitis (VAPP) or vaccine-derived polioviruses (VDPV) infection when inadvertently expose to poliovirus vaccine, oral (OPV). A pilot study was initiated to describe the epidemiology of immunodeficiency-associated VDPV (iVDPV) and to estimate the risk of iVDPV shedding among individuals with PID. Children under 18 years of age newly diagnosed with PID were recruited for investigation and tested for poliovirus excretion. Children with poliovirus-positive stool samples had regular follow-up testing for poliovirus excretion and determination of clinical prognosis. A patient with severe combined immunodeficiency (SCID) with compound heterozygous mutations in the RAG1 gene was found to be excreting Sabin-like type 3 (SL3) poliovirus. Excretion stopped six weeks after hematopoietic stem-cell transplantation (HSCT). Graft versus host disease (GVHD) and poor graft function (PGF) occurred after HSCT, resulting in failure of hematopoiesis and immune system reconstitution. Given deficient innate and adaptive immunity, immune-mediated destruction of gastrointestinal (GI) tract caused by GVHD and inflammatory diarrheal illness of the girl may have contributed to her clearance of SL3 poliovirus. Intermittent surveillance of immune system parameters for iVDPV excreters receiving HSCT should be included in the PID surveillance program for further understanding poliovirus clearance mechanisms.}, }
@article {pmid40170504, year = {2025}, author = {Zheng, Y and Chen, J and Zhang, Y and Guan, H and Deng, S and Chang, D and Wang, Y and Lu, J and Zhou, X and Xie, Q and Song, J and Huang, M}, title = {Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.8474}, pmid = {40170504}, issn = {1099-1573}, support = {2022YFC3501205//National Key Research and Development Program of China Stem Cell and Translational Research/ ; 2021FX02//Collaborative Innovation Platform Project of Fuxiaquan National Innovation Demonstration Zone/ ; 82274080//National Natural Science Foundation of China Projects/ ; //Research Support Program Fellowship, Western Sydney University/ ; }, abstract = {Gut microbiota and bile acid metabolism play crucial roles in the progression of nonalcoholic fatty liver disease (NAFLD). Early evidence demonstrates that Ginsenoside Re (Re) possesses pharmacological effects on NAFLD, but its mechanisms of action are not well understood. This study aimed to investigate the hepatic protective effects of Re in NAFLD and elucidate relevant mechanisms. The effects of Re treatments (10, 20, or 40 mg/kg) against high-fat diet-induced NAFLD were initially tested on male C57BL/6 mice. Then, a separate mouse group received Re with or without antibiotics to confirm the regulatory role of microbiota in the effect of Re. Finally, another group of mice received fecal microbiota transplantation (FMT) from the initial experiment of NAFLD mice to further investigate the mechanistic role of gut microbiota. Re significantly improved liver function by reducing hepatic lipid accumulation, injury and hepatocyte steatosis, and inflammation. The liver protection was mediated by the regulation of gut microbiota as evidenced by restored intestinal barrier integrity, normalized Firmicutes/Bacteroidota ratio, enhanced abundances of Adlercreutzia equolifaciens, and reduced Faecalibaculum rodentium. Following that, Re reduced total and primary bile acids and downregulated bile acid synthesis genes and proteins such as farnesoid X receptor and cytochrome P450 family 7 subfamily A member 1. The co-administration of antibiotic cocktail counteracted the effect of Re against NAFLD. Further, the results obtained from the FMT animal study confirmed that Re's liver protective effects were at least partly driven by the regulation of gut microbiota. Re modulated bile salt hydrolase-related microbial genera to alter bile acid synthesis pathways, thereby inhibiting NAFLD progression.}, }
@article {pmid40168721, year = {2025}, author = {Shi, Y and Jiang, M and Zhu, W and Chang, K and Cheng, X and Bao, H and Peng, Z and Hu, Y and Li, C and Fang, F and Song, J and Jian, C and Chen, J and Shu, X}, title = {Cyclosporine combined with dexamethasone regulates hepatic Abca1 and PPARα expression and lipid metabolism via butyrate derived from the gut microbiota.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {186}, number = {}, pages = {118017}, doi = {10.1016/j.biopha.2025.118017}, pmid = {40168721}, issn = {1950-6007}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Cyclosporine/pharmacology/administration &amp; dosage ; *Dexamethasone/pharmacology/administration &amp; dosage ; *Lipid Metabolism/drug effects ; *Butyrates/metabolism ; *PPAR alpha/metabolism/genetics ; *Liver/metabolism/drug effects ; Mice ; *ATP Binding Cassette Transporter 1/metabolism/genetics ; Male ; Macaca mulatta ; Immunosuppressive Agents/pharmacology ; Dysbiosis ; }, abstract = {Immunosuppression often leads to drastic metabolic, hormonal, and physiological disorders. Changes in the gut microbiota are believed to be one of the factors contributing to these disorders, but the association remains uncertain. Clinical studies can be complicated by confounding variables, such as diet and other drivers of heterogeneity in human microbiomes. In this study, we identified pronounced gut microbiome signatures in rhesus macaques (RMs) with immunosuppression-induced lipid metabolism disorders following cyclosporine combined with dexamethasone. Furthermore, we observed similar changes in the gut microbiota of mice with immunosuppression-induced lipid metabolism disorders, which were associated with short-chain fatty acid metabolism. ELISA showed that immunosuppression significantly reduced the levels of butyric acid in both feces and serum of mice. Spearman correlation analysis identified a significant correlation between serum butyric acid levels and gut microbial dysbiosis induced by immunosuppression, particularly in relation to f_Lachnospiraceae, g_unidentified_Ruminococcaceae, and s_Clostridium leptum. Additionally, mice transplanted with gut microbiota from immunosuppressed mice exhibited hepatic lipid metabolism disorders, and RNA sequencing revealed significant downregulation of ABC transporters and PPARα in the liver, which was closely associated with lipid transport and metabolism, particularly Abca1. Moreover, butyric acid supplementation alleviated hepatic lipid metabolism disorders and upregulated the expression of Abca1 and PPARα in mice transplanted with immunosuppression-induced gut microbiota. Thus, we propose that the combination of cyclosporine and dexamethasone regulates the expression of hepatic Abca1 and PPARα by modulating the gut microbiota and its derived butyrate, particularly Lachnospiraceae and Clostridium leptum, further regulating hepatic lipid metabolism.}, }
@article {pmid40168084, year = {2025}, author = {Ishikawa, D and Watanabe, H and Nomura, K and Zhang, X and Maruyama, T and Odakura, R and Koma, M and Shibuya, T and Osada, T and Fukuda, S and Nakahara, T and Terauchi, J and Nagahara, A and Yamada, T}, title = {Patient-donor similarity and donor-derived species contribute to the outcome of fecal microbiota transplantation for ulcerative colitis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {19}, number = {4}, pages = {}, doi = {10.1093/ecco-jcc/jjaf054}, pmid = {40168084}, issn = {1876-4479}, support = {JP16K09328//Japan Society for the Promotion of Science/ ; //Kyowa Kirin Co., Ltd./ ; //Kyowa Hakko Bio Co., Ltd./ ; //Kirin Holdings Co., Ltd./ ; //Metagen Therapeutics Inc./ ; JP21ae0121038//Japan Agency for Medical Research and Development/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy/microbiology ; Male ; Female ; Middle Aged ; Adult ; Feces/microbiology ; Anti-Bacterial Agents/therapeutic use ; Gastrointestinal Microbiome ; Treatment Outcome ; Tissue Donors ; Severity of Illness Index ; *Donor Selection ; }, abstract = {BACKGROUND AND AIMS: Clinical applications of fecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. However, whether the beneficial effects of FMT are due to the transfer and colonization of donor-derived species in patients remains unclear. Here, we investigated the factors affecting the efficacy of the administration of triple antibiotics (A-FMT) and the criteria for appropriate donor and patient-donor matching.<br><br>METHODS: Ninety-seven patients with active UC who were enrolled between March 2014 and October 2019 underwent FMT. The clinical features were assessed based on a reduction in Lichtiger's clinical activity index 4 weeks after A-FMT, with long-term responders (LTR) defined as those with no increase or intensification within 12 months after A-FMT. Microbiome analysis was performed on 147 fecal samples (pre-A-FMT, post-A-FMT, and donor) from 49 patient-donor combinations that were assigned using the one-patient-to-one-donor strategy.<br><br>RESULTS: Of the 97 patients, 61 achieved a clinical response, and of those, 35 were classified as having clinical remission. The efficacy of A-FMT was affected by UC severity and previous administration of steroids (P&#x2005;=&#x2005;.027), immunosuppressants (P&#x2005;=&#x2005;.049), and biologics (P&#x2005;=&#x2005;.029). Effective donors were rich in taxa such as Bacteroidota, which are lost in UC, and the abundances of "patient-origin" and "new-amplicon sequence variant" taxa were significantly lower in Responders compared to Nonresponders (Remission; P&#x2005;=&#x2005;.03, LTR; P&#x2005;=&#x2005;.05). "Donor-derived" amplicon sequence variant sequences, Oscillospiraceae UCG-002 and Alistipes, were significantly enriched in Responders (P&#x2005;<&#x2005;.05). Our results showed that the taxonomic composition of patients and the similarity of Bacteroides and butyric-acid-producing bacteria in the patient-donor microbiota significantly influenced A-FMT efficacy (P&#x2005;<&#x2005;.05).<br><br>CONCLUSIONS: This study provides important insights for developing patient-tailored FMT-based therapies for UC.}, }
@article {pmid40167852, year = {2025}, author = {Xiang, M and Wu, S and Liu, M and Zhang, B and Xia, X and Tan, W and Xiang, S}, title = {Iota-carrageenan oligosaccharide ameliorates DSS-induced colitis in mice by mediating gut microbiota dysbiosis and modulating SCFAs-PI3K-AKT pathway.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {}, pmid = {40167852}, issn = {1568-5608}, support = {NO.2024AFD252//the Natural Science Foundation of Hubei Province/ ; }, abstract = {Iota-carrageenan oligosaccharides (iCOs), derived from marine red algae, are traditionally used as antithrombotic and anti-inflammatory agents in folk medicinal practice. Despite the prevailing emphasis on these aspects in their applications, the potential of iCOs as a prebiotic agent for gut health and its subsequent impact on intestinal disorders such as colitis remains largely unexplored. A DSS-induced colitis model was employed in C57BL/6 male mice to analyze the gut microbiota via 16S rRNA sequencing. Fecal microbiota transplantation (FMT) was used to assess the therapeutic effects of iCOs on colitis. RNA sequencing (RNA-Seq) identified pathways and genes affected by iCOs. ELISA measured inflammatory cytokines, while western blot and RT-qPCR evaluated protein and gene expressions, respectively. The iCOs increased beneficial bacteria, such as Lactobacillus, Bifidobacterium, and Akkermansia. They enhanced short-chain fatty acid production and upregulated GPR41, GPR43, and GPR109A mRNA, influencing cytokine secretion. The iCOs reduced mRNA of SPHK1, BDKRB1, LCN2, and so on, potentially through PI3K-Akt pathway inhibition, and promoted tight junction protein expression. Our findings highlight the novel therapeutic potential of iCOs in colitis, indicating a multifaceted approach to treatment that includes gut microbiota modulation, intestinal barrier restoration, and the suppression of inflammatory responses.}, }
@article {pmid40166981, year = {2025}, author = {Huang, M and Ji, Q and Huang, H and Wang, X and Wang, L}, title = {Gut microbiota in hepatocellular carcinoma immunotherapy: immune microenvironment remodeling and gut microbiota modification.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2486519}, pmid = {40166981}, issn = {1949-0984}, mesh = {Humans ; *Carcinoma, Hepatocellular/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; *Liver Neoplasms/immunology/therapy/microbiology ; *Immunotherapy ; *Tumor Microenvironment/immunology ; *Probiotics/therapeutic use/administration &amp; dosage ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited treatment options at advanced stages. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, plays a pivotal role in regulating immune responses through the gut-liver axis. Emerging evidence underscores its impact on HCC progression and the efficacy of immunotherapy. This review explores the intricate interactions between gut microbiota and the immune system in HCC, with a focus on key immune cells and pathways involved in tumor immunity. Additionally, it highlights strategies for modulating the gut microbiota - such as fecal microbiota transplantation, dietary interventions, and probiotics - as potential approaches to enhancing immunotherapy outcomes. A deeper understanding of these mechanisms could pave the way for novel therapeutic strategies aimed at improving patient prognosis.}, }
@article {pmid40166958, year = {2025}, author = {Zhang, Z and Zhu, T and Li, Y and Yu, B and Tao, H and Zhao, H and Cui, B}, title = {Butyrate Regulates Intestinal DNA Virome and Lipopolysaccharide Levels to Prevent High-Fat Diet-Related Liver Damage in Rats.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {14}, pages = {8277-8289}, doi = {10.1021/acs.jafc.4c07966}, pmid = {40166958}, issn = {1520-5118}, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Lipopolysaccharides/metabolism ; Rats ; Gastrointestinal Microbiome/drug effects ; Male ; *Non-alcoholic Fatty Liver Disease/metabolism/microbiology/etiology/virology/prevention &amp; control/drug therapy ; *Butyrates/administration &amp; dosage/metabolism ; Humans ; Rats, Sprague-Dawley ; *Virome/drug effects ; Liver/metabolism/drug effects/injuries ; *Intestines/virology/microbiology/drug effects ; *Bacteriophages/genetics/metabolism ; Bacteria/metabolism/genetics/virology/isolation &amp; purification ; Hep G2 Cells ; }, abstract = {As the adsorption receptor of bacteriophage tail protein, bacterial lipopolysaccharide (LPS) is a main culprit responsible for nonalcoholic fatty liver disease (NAFLD) caused by high-fat diets. However, few studies have focused on how the interaction between intestinal bacteriophages and bacterial LPS affects the development and progression of NAFLD. Herein, we determined that excessive fat intake significantly increases the levels of endogenous LPS, while the administration of beneficial metabolites of the intestinal microbiota (specifically butyrate) alleviated hepatic injury in rats. The beneficial mechanism of butyrate was attributed to the reprogramming of the structure of the intestinal DNA virome (primarily, phageome). Butyrate possesses the potential to augment bacteriophagic microbial diversity, thereby potentially facilitating interactions between intestinal bacteriophages and bacterial LPS (in the case of homologous phage), further improving mitochondrial dysfunction and reactive oxygen species production, which, in turn, lowered HepG2 cell damage. Likewise, fecal phage transplantation further confirmed that intestinal phages from rats that received butyrate could effectively interact with bacterial LPS to reduce liver damage in rats. Taken together, modifying the intestinal phageome is a promising treatment option for high-fat diet-related NAFLD.}, }
@article {pmid40166696, year = {2025}, author = {Halvorsen, N and Hassan, C and Correale, L and Pilonis, N and Helsingen, LM and Spadaccini, M and Repici, A and Foroutan, F and Olav Vandvik, P and Sultan, S and Løberg, M and Kalager, M and Mori, Y and Bretthauer, M}, title = {Benefits, burden, and harms of computer aided polyp detection with artificial intelligence in colorectal cancer screening: microsimulation modelling study.}, journal = {BMJ medicine}, volume = {4}, number = {1}, pages = {e001446}, pmid = {40166696}, issn = {2754-0413}, abstract = {OBJECTIVE: To estimate the benefits, burden, and harms of implementing computer aided detection (CADe) of polyps in colonoscopy of population based screening programmes for colorectal cancer.<br><br>DESIGN: Microsimulation modelling study.<br><br>SETTING: Cost effectiveness working package in the OperA (optimising colorectal cancer prevention through personalised treatment with artificial intelligence) project. A parallel guideline committee panel (BMJ Rapid recommendation) was consulted in defining the screening interventions and selection of outcome measures.<br><br>POPULATION: Four cohorts of 100&#x2009;000 European individuals aged 60-69 years.<br><br>INTERVENTION: The intervention was one screening of colonoscopy and a screening of colonoscopy after faecal immunochemical test every other year with CADe. The comparison group had the same screening every other year without CADe.<br><br>MAIN OUTCOME MEASURES: Benefits (colorectal cancer incidence and death), burden (surveillance colonoscopies), and harms (colonoscopy related adverse events) over 10&#x2009;years were measured. The certainty in each outcome was assessed by use of the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.<br><br>RESULTS: For 100&#x2009;000 individuals participating in colonoscopy screening, 824 (0.82%) were diagnosed with colorectal cancer within 10 years without CADe versus 713 (0.71%) with CADe (risk difference -0.11% (95% CI -0.43% to 0.21%)). For faecal immunochemical test screening colonoscopy, the risk was 5.82% (n=5820) without CADe versus 5.77% (n=5770) with CADe (difference -0.05% (-0.33% to 0.15%)). The risk of surveillance colonoscopy increased from 26.45% (n=26 453) to 32.82% (n=32 819) (difference 6.37% (5.8% to 6.9%)) for colonoscopy screening and from 52.26% (n=52 263) to 53.08% (n=53 082) (difference 0.82% (0.38% to 1.26%)) for faecal immunochemical test screening colonoscopy. No significant differences were noted in adverse events related to the colonoscopy between CADe and no CADe. The model estimates were sensitive to the assumed effects of screening on colorectal cancer risk and of CADe on adenoma detection rates. All outcomes were graded as low certainty.<br><br>CONCLUSION: With low certainty of evidence, adoption of CADe in population based screening provides small and uncertain clinical meaningful benefit, no incremental harms, and increased surveillance burden after screening.}, }
@article {pmid40165964, year = {2025}, author = {Ding, W and Cheng, Y and Liu, X and Zhu, Z and Wu, L and Gao, J and Lei, W and Li, Y and Zhou, X and Wu, J and Gao, Y and Ling, Z and Jiang, R}, title = {Harnessing the human gut microbiota: an emerging frontier in combatting multidrug-resistant bacteria.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1563450}, pmid = {40165964}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; *Dysbiosis/microbiology ; *Anti-Bacterial Agents/therapeutic use/pharmacology ; Bacterial Infections/microbiology/immunology/drug therapy ; Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; Bacteria/drug effects ; Animals ; }, abstract = {Antimicrobial resistance (AMR) has become a major and escalating global health threat, undermining the effectiveness of current antibiotic and antimicrobial therapies. The rise of multidrug-resistant bacteria has led to increasingly difficult-to-treat infections, resulting in higher morbidity, mortality, and healthcare costs. Tackling this crisis requires the development of novel antimicrobial agents, optimization of current therapeutic strategies, and global initiatives in infection surveillance and control. Recent studies highlight the crucial role of the human gut microbiota in defending against AMR pathogens. A balanced microbiota protects the body through mechanisms such as colonization resistance, positioning it as a key ally in the fight against AMR. In contrast, gut dysbiosis disrupts this defense, thereby facilitating the persistence, colonization, and dissemination of resistant pathogens. This review will explore how gut microbiota influence drug-resistant bacterial infections, its involvement in various types of AMR-related infections, and the potential for novel microbiota-targeted therapies, such as fecal microbiota transplantation, prebiotics, probiotics, phage therapy. Elucidating the interactions between gut microbiota and AMR pathogens will provide critical insights for developing novel therapeutic strategies to prevent and treat AMR infections. While previous reviews have focused on the general impact of the microbiota on human health, this review will specifically look at the latest research on the interactions between the gut microbiota and the evolution and spread of AMR, highlighting potential therapeutic strategies.}, }
@article {pmid40165428, year = {2025}, author = {Wang, L and Shao, L and Gao, YC and Liu, J and Li, XD and Zhou, J and Li, SF and Song, YL and Liu, B and Zhang, W and Huang, WH}, title = {Panax notoginseng Saponins Alleviate Inflammatory Bowel Disease via Alteration of Gut Microbiota-Bile Acid Metabolism.}, journal = {The American journal of Chinese medicine}, volume = {53}, number = {2}, pages = {567-596}, doi = {10.1142/S0192415X25500223}, pmid = {40165428}, issn = {1793-6853}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Saponins/pharmacology/isolation &amp; purification/therapeutic use/administration &amp; dosage ; *Panax notoginseng/chemistry ; *Bile Acids and Salts/metabolism ; *Inflammatory Bowel Diseases/drug therapy/metabolism/microbiology ; Animals ; Th17 Cells/immunology ; T-Lymphocytes, Regulatory/immunology ; Male ; *Phytotherapy ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {Bile acid metabolism mediated by gut microbiota is significantly related to immunity regulation that plays an important role in the development and treatment of inflammatory bowel disease (IBD). Our previous study has demonstrated that Panax notoginseng saponins (PNS) alleviate colitis due to the regulation of T helper 17/Regulatory T cells (Th17/Treg) balance via gut microbiota. However, the effects and mechanism of PNS on colitis pertinent to bile acid metabolism mediated by gut microbiota remain elusive. This study aims to investigate the anti-colitis mechanism of PNS by regulating the Th17/Treg balance pertinent to gut microbiota-bile acid metabolism. Results showed that PNS significantly decreased the relative abundance of Allobaculum, Dubosiella, Muribaculum, and Alistipes, and up-regulated the relative contents of conjugated bile acids, such as TCA and TCDCA. Fecal microbiota transplantation (FMT) showed that the gut microbiota remodeled by PNS had a regulatory effect on bile acid metabolism, and up-regulated the relative contents of TCA and TCDCA, which alleviated IBD and promoted Treg cell expression in vivo and in vitro. Taken together, PNS could reshape the profiling of gut microbiota to generate more TCA and TCDCA, which improve the balance of Th17/Treg to exert anti-IBD effects.}, }
@article {pmid40164697, year = {2025}, author = {Jia, L and Ke, Y and Zhao, S and Liu, J and Luo, X and Cao, J and Liu, Y and Guo, Q and Chen, WH and Chen, F and ,  and Wang, J and Wu, H and Ding, J and Zhao, XM}, title = {Metagenomic analysis characterizes stage-specific gut microbiota in Alzheimer's disease.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {40164697}, issn = {1476-5578}, abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a decade-long preclinical pathological period that can be divided into several stages. Emerging evidence has revealed that the microbiota-gut-brain axis plays an important role in AD pathology. However, the role of gut microbiota in different AD stages has not been well characterized. In this study, we performed fecal shotgun metagenomic analysis on a Chinese cohort with 476 participants across five stages of AD pathology to characterize stage-specific alterations in gut microbiota and evaluate their diagnostic potential. We discovered extensive gut dysbiosis that is associated with neuroinflammation and neurotransmitter dysregulation, with over 10% of microbial species and gene families showing significant alterations during AD progression. Furthermore, we demonstrated that microbial gene families exhibited strong diagnostic capabilities, evidenced by an average AUC of 0.80 in cross-validation and 0.75 in independent external validation. In the optimal model, the most discriminant gene families are primarily involved in the metabolism of carbohydrates, amino acids, energy, glycan and vitamins. We found that stage-specific microbial gene families in AD pathology could be validated by an in vitro gut simulator and were associated with specific genera. We also observed that the gut microbiota could affect the progression of cognitive decline in 5xFAD mice through fecal microbiota transplantation, which could be used for early intervention of AD. Our multi-stage large cohort metagenomic analysis demonstrates that alterations in gut microbiota occur from the very early stages of AD pathology, offering important etiological and diagnostic insights.}, }
@article {pmid40163879, year = {2025}, author = {Cintosun, A and Jamal, I and Samnani, S and Song, YN and Bretthauer, M}, title = {Gastroenterology/Hepatology: What You May Have Missed in 2024.}, journal = {Annals of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.7326/ANNALS-25-00959}, pmid = {40163879}, issn = {1539-3704}, abstract = {This article highlights selected major advances in gastroenterology and hepatology from 2024 that are relevant for internal medicine specialists. In colorectal cancer (CRC) screening, new developments include a head-to-head comparison of different fecal immunochemical tests and a new blood-based DNA screening test, benefits and harms of artificial intelligence-assisted colonoscopy, and adenoma detection rate improvement and risk for cancer. Treatment options for metabolic dysfunction-associated steatotic liver disease now include resmetirom, a recently approved drug for treatment of patients with moderate-to-severe fibrosis, and liver transplantation may now be an option in patients with unresectable colorectal liver metastases. Also featured are new data on the efficacy of indomethacin and pancreatic stent placement for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography and news on the efficacy and safety of zastaprazan, a new potassium-competitive acid blocker for reflux esophagitis. Finally, a recent randomized trial is highlighted that has dispelled concerns about potential harms of proton-pump inhibitors for stress ulcer prophylaxis in patients receiving invasive mechanical ventilation.}, }
@article {pmid40162905, year = {2025}, author = {Sigtryggsson, AT and Helgason, KO and Bjarnason, A and Gottfredsson, M}, title = {[Clostridioides difficile infections at Landspítali University Hospital 2017-2022].}, journal = {Laeknabladid}, volume = {111}, number = {4}, pages = {158-165}, doi = {10.17992/lbl.2025.04.834}, pmid = {40162905}, issn = {1670-4959}, mesh = {Humans ; *Hospitals, University ; Female ; Male ; Iceland/epidemiology ; Incidence ; *Anti-Bacterial Agents/therapeutic use ; Risk Factors ; Time Factors ; Aged ; Middle Aged ; *Clostridium Infections/epidemiology/diagnosis/microbiology/therapy/mortality/drug therapy ; *Recurrence ; Treatment Outcome ; *Clostridioides difficile/pathogenicity/isolation &amp; purification/drug effects ; Cross Infection/epidemiology/diagnosis/microbiology/mortality/drug therapy ; Aged, 80 and over ; Adult ; Community-Acquired Infections/epidemiology/diagnosis/microbiology/therapy/mortality/drug therapy ; }, abstract = {OBJECTIVE: To investigate the epidemiology, severity, treatment, and prognosis of patients with C. difficile infections (CDI) diagnosed at Landspítali University Hospital from 2017-2022.<br><br>MATERIALS AND METHODS: The study population consisted of adult patients at Landsp&#xed;tali with double-positive (PCR + ELISA) diagnostic tests. If the same patient had two or more positive samples within a 28-day period, they were considered to reflect the same infection, and the latter samples were excluded.<br><br>RESULTS: Overall, 358 CDI were identified in 301 patients. The majority of cases were diagnosed in women (59.5%). The incidence of healthcare-associated CDI was 3.23 infections/10.000 in-hospital days (range 2.65 - 3.26). Incidence of community-associated CDI was 0.57 infections/10.000 inhabitants of the Reykjavik metropolitan area. Incidence was positively correlated with increasing age and remained similar throughout the study period. The recurrence rate during the study period was 15.3% with a mean follow-up period of 1.6 person-years. At least 85.5% of patients had taken antibiotics within a month before diagnosis, most commonly from the penicillin class (57.8%), followed by cephalosporins (51.5%). More than half (54.7%) of patients had taken proton pump inhibitors preceding diagnosis. Metronidazole was the most common initial treatment (63.0%). Of these, 29.4% of cases required further treatment within 28 days of treatment start. Fecal microbiota transplantation was performed in 13 cases. The 30-day all-cause mortality rate was 7.3%.<br><br>CONCLUSIONS: The incidence of CDI at Landsp&#xed;tali has remained stable and comparable to what has been reported in Europe during the same period. Most patients had one or more risk factors present. Most received antibiotics as treatment, most commonly metronidazole. The results of this study indicate that incidence and clinical presentation of CDI in Iceland are stable, whilst novel treatment options look promising.}, }
@article {pmid40161742, year = {2025}, author = {Wong, MK and Armstrong, E and Heirali, AA and Schneeberger, PHH and Chen, H and Cochrane, K and Sherriff, K and Allen-Vercoe, E and Siu, LL and Spreafico, A and Coburn, B}, title = {Assessment of ecological fidelity of human microbiome-associated mice in observational studies and an interventional trial.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40161742}, issn = {2692-8205}, support = {UM1 CA186644/CA/NCI NIH HHS/United States ; }, abstract = {Composition and function of the gut microbiome is associated with diverse health conditions and treatment responses. Human microbiota-associated (HMA) mouse models are used to establish causal links for these associations but have important limitations. We assessed the fidelity of HMA mouse models to recapitulate ecological responses to a microbial consortium using stools collected from a human clinical trial. HMA mice were generated using different routes of consortium exposure and their ecological features were compared to human donors by metagenomic sequencing. HMA mice were more similar in gut composition to other mice than their respective human donors, with taxa including Akkermansia muciniphila and Bacteroides species enriched in mouse recipients. A limited repertoire of microbes was able to engraft into HMA mice regardless of route of consortium exposure. In publicly available HMA mouse datasets from four distinct health conditions, we confirmed our observation that a taxonomically restricted set of microbes reproducibly engrafts in HMA mice and observed that stool microbiome composition of HMA mice were more like other mice than their human donor. Our data suggest that HMA mice are limited models to assess the ecological impact of microbial consortia, with ecological effects in HMA mice being more strongly associated with host species than donor stool ecology or ecological responses to treatment in humans. Comparisons to published studies suggest this may be due to comparatively large host-species effects that overwhelm ecological effects of treatment in humans that HMA models aim to recapitulate.}, }
@article {pmid40161578, year = {2025}, author = {Zhong, XS and Lopez, KM and Krishnachaitanya, SS and Liu, M and Xiao, Y and Ou, R and Nagy, HI and Kochkarian, T and Powell, DW and Fujise, K and Li, Q}, title = {Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.03.13.643179}, pmid = {40161578}, issn = {2692-8205}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with significant extraintestinal manifestations, including cardiovascular derangements. However, the molecular mechanisms underlying the cardiac remodeling and dysfunction remain unclear.<br><br>METHODS: We investigated the effects of chronic colitis on the heart using two mouse models: DSS-induced colitis and Il10 [-/-] spontaneous colitis. Echocardiography was employed to assess heart function and molecular characterization was performed using bulk RNA-sequencing, RT-qPCR, and western blot.<br><br>RESULTS: Both models exhibited significant cardiac impairment, including reduced ejection fraction and fractional shortening as well as increased collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed upregulation of fibrosis markers (i.e. COL1A1, COL3A1, Fibronectin) and &#x3b2;-catenin reactivation, indicating a pro-fibrotic cardiac environment. Each model yielded common upregulation of eicosanoid-associated and inflammatory genes (Cyp2e1 , Map3k6 , Pck1 , Cfd), and model-specific alterations in pathways regulating cAMP- and cGMP-signaling, arachidonic and linoleic acid metabolism, Cushing syndrome-related genes, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, while Il10 [-/-] colitis yielded 105 dysregulated genes, revealing distinct molecular pathways driving cardiac dysfunction. Importantly, therapeutic fecal microbiota transplantation (FMT) restored heart function in both models, characterized by reduced fibrosis markers and downregulated pro-inflammatory genes (Lbp and Cdkn1a in Il10 [-/-] mice and Fos in DSS mice), while also mitigating intestinal inflammation. Post-FMT cardiac RNA-sequencing revealed significant gene expression changes, with three altered genes in DSS mice and 67 genes in Il10 [-/-] mice. Notably, Il10 [-/-] mice showed relatively less cardiac recovery following FMT, highlighting IL-10's cardioprotective and anti-inflammatory contribution.<br><br>CONCLUSIONS: Our findings elucidate novel insights into colitis-induced cardiac remodeling and dysfunction and suggest that FMT mitigates cardiac dysfunction by attenuating systemic inflammation and correcting gut dysbiosis. This study underscores the need for further evaluation of gut-heart interactions and microbiome-based therapies to improve cardiovascular health in IBD patients.}, }
@article {pmid40161500, year = {2025}, author = {Dai, W and Chen, X and Zhou, H and Liu, N and Jin, M and Guo, Z}, title = {Microbiota modulation for infectious complications following allogeneic hematopoietic stem cell transplantation in pediatric hematological malignancies.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1509612}, pmid = {40161500}, issn = {2296-2360}, abstract = {The intervention of microbiota modulation in the treatment of infection complications after allogeneic hematopoietic stem cell transplantation in pediatric patients with hematological malignancies has shown potential benefits. Through the use of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), these interventions modulate the gut microbiota and enhance immune function to prevent and treat infections. They have been shown to reduce the incidence of diarrhea and intestinal infections, mitigate the issue of antibiotic resistance, and promote the recovery of gut microbiota. Future research is needed to further assess the safety and efficacy of these interventions and to establish standardized treatment protocols.}, }
@article {pmid40160347, year = {2025}, author = {Tucker, EC and Angelica, B and Mathias, RM and Edwards, L and Bryant, RV and Costello, SP}, title = {Outcomes of Fecal Microbiota Transplantation for Clostridioides difficile Infection in South Australia.}, journal = {Open forum infectious diseases}, volume = {12}, number = {4}, pages = {ofaf149}, pmid = {40160347}, issn = {2328-8957}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) sourced from a bank of prescreened anaerobically processed frozen donor stool has been available in South Australia since 2013. This study aimed to evaluate the real-world clinical and safety outcomes of FMT for recurrent, refractory, and/or severe or fulminant Clostridioides difficile infection (CDI) facilitated via this centralized facility.<br><br>METHODS: Donor screening test data were prospectively collected on all donors who passed prescreening evaluations between April 2013 and August 2023. The South Australian FMT for CDI database prospectively recorded outcomes for consecutive patients who underwent FMT for CDI from August 2013 to May 2023 in South Australia.<br><br>RESULTS: An overall 98 potential donors passed prescreening assessments and underwent laboratory screening tests: 32 (33%) had tests that failed, 5 (5%) had incomplete screening, and 61 (62%) passed. Detection of an extended-spectrum &#x3b2;-lactamase-producing organism (9/65, 14%) was the common reason for ineligibility following completion of screening tests. In total 220 cases of CDI were recorded, and follow-up data were available in 216. Primary cure occurred in 84% of cases (182/216): 88% (132/150) for recurrent CDI, 76% (50/66) for refractory CDI, 85% (51/60) for severe disease, and 65% (17/26) for fulminant disease. Repeat FMT was delivered in 23 of 34 cases (68%), with secondary cure in 74% (17/23 cases). Serious adverse events were observed in 6 patients overall (3%). No deaths were directly attributable to FMT.<br><br>CONCLUSIONS: FMT was safe and efficacious for management of recurrent and refractory CDI over a 10-year period in a real-world prospective Australian cohort. Further studies to optimize the use of FMT for severe and fulminant CDI are warranted.}, }
@article {pmid40160324, year = {2025}, author = {Cao, Z and Gao, T and Bajinka, O and Zhang, Y and Yuan, X}, title = {Fecal microbiota transplantation-current perspective on human health.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1523870}, pmid = {40160324}, issn = {2296-858X}, abstract = {Recently, microbiome medicine has attracted the attention of researchers. While this rapidly growing medical approach for various diseases and disorders is changing the paradigm, it is imperative to weigh both its benefits and the associated risk factors. For instance, manipulation of the gut microbiota (GM) has positive effects on metabolic and neurodegenerative diseases. Notably, fecal microbiota transplantation (FMT), a complex method, has shown promise; however, many doubt its feasibility without adverse effects on human health. Given the number of human clinical trials investigating FMT for the treatment of various disorders, this review summarizes recent findings on its impact on human health. This review summarizes the metabolic responses associated with FMT and their reversal effects on gastrointestinal infections, behavioral changes, and immune responses. Additionally, this review discusses the role of FMT in antimicrobial resistance and its co-supplementation effects on human health, safety, potential risks, limitations, prospects, and recommendations. Although this review does not cover all the studies in the database, the searched terms for FMT and human health in clinical trials are sufficient to provide a summary of the current perspective.}, }
@article {pmid40158522, year = {2025}, author = {Bretthauer, M and Kalager, M}, title = {First head-to-head trial of colonoscopy versus faecal testing for colorectal cancer screening.}, journal = {Lancet (London, England)}, volume = {405}, number = {10486}, pages = {1204-1206}, doi = {10.1016/S0140-6736(25)00288-0}, pmid = {40158522}, issn = {1474-547X}, }
@article {pmid40157463, year = {2025}, author = {Han, Y and Zhang, Y and Chen, J and Jiang, S and Zheng, Y and Xu, Y and Li, Y and Kong, J and Yu, X and Du, H}, title = {Iron overload exacerbates metabolic dysfunction-associated steatohepatitis via the microbiota-gut-liver axis through lipopolysaccharide-mediated Akr1b8 activation.}, journal = {Free radical biology &amp; medicine}, volume = {233}, number = {}, pages = {196-208}, doi = {10.1016/j.freeradbiomed.2025.03.039}, pmid = {40157463}, issn = {1873-4596}, mesh = {Animals ; *Iron Overload/metabolism/complications/pathology/genetics/microbiology ; *Gastrointestinal Microbiome ; *Lipopolysaccharides/metabolism ; Mice ; Liver/metabolism/pathology ; Mice, Knockout ; *Aldo-Keto Reductases/metabolism/genetics ; Male ; Mice, Inbred C57BL ; *Fatty Liver/pathology/metabolism/microbiology ; Hemochromatosis Protein/genetics ; Iron/metabolism ; Disease Models, Animal ; Methionine/deficiency ; Lipid Metabolism ; }, abstract = {Iron homeostatic is closely linked to the development of metabolic dysfunction-associated steatohepatitis (MASH). However, the underlying mechanisms remain poorly understood. HFE knockout (KO) mice were used to generate mild iron-overload models. MASH was induced by feeding mice a methionine- and choline-deficient (MCD) diet for 4 weeks. Iron overload significantly exacerbated the pathologies of MCD-induced MASH, including liver injury, hepatic lipid accumulation, inflammation, and fibrosis. Additionally, iron overload reshaped the composition of gut microbiota, and fecal microbiota transplantation assay proved that gut microbiota from iron-overload mice contributed to hepatic lipid accumulation in control mice. Furthermore, iron overload-induced dysbacteriosis altered the metabolite profiles, reducing short-chain fatty acid levels and increasing lipopolysaccharide (LPS) levels. Notably, elevated LPS levels upregulated the expression of aldo-keto reductase family 1 member B8 (Akr1b8), which accelerated lipid accumulation and inflammation in hepatocytes. Above results indicated that iron overload promoted MASH progression through the microbiota-gut-liver axis, mediated by LPS-induced activation of Akr1b8. These findings highlight the critical role of iron homeostasis and gut microbiota in MASH pathogenesis.}, }
@article {pmid40157004, year = {2025}, author = {Rahimi, A and Baghernejadan, Z and Hazrati, A and Malekpour, K and Samimi, LN and Najafi, A and Falak, R and Khorramdelazad, H}, title = {Combination therapy with immune checkpoint inhibitors in colorectal cancer: Challenges, resistance mechanisms, and the role of microbiota.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {186}, number = {}, pages = {118014}, doi = {10.1016/j.biopha.2025.118014}, pmid = {40157004}, issn = {1950-6007}, mesh = {Humans ; Animals ; Drug Combinations ; *Immune Checkpoint Inhibitors/therapeutic use ; *Microbiota ; *Colorectal Neoplasms/drug therapy ; *Drug Resistance, Neoplasm ; Tumor Microenvironment/drug effects ; Clinical Trials as Topic ; }, abstract = {Colorectal cancer (CRC) is still one of the leading causes of cancer deaths worldwide. Even though there has been progress in cancer immunotherapy, the results of applying immune checkpoint inhibitors (ICIs) have been unsatisfactory, especially in microsatellite stable (MSS) CRC. Single-agent ICIs that target programmed cell death-1 (PD-1)/ PD-L1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell Ig- and mucin-domain-containing molecule-3 (TIM-3), and lymphocyte activation gene (LAG)-3 have emerged as having specific benefits. However, many primary and secondary resistance mechanisms are available in the tumor microenvironment (TME) that prevent it from happening. Combination strategies, such as the use of anti-PD-1 and anti-CTLA-4, can be effective in overcoming these resistance pathways, but toxicities remain a significant concern. Moreover, ICIs have been integrated with various treatment modalities, including chemotherapy, radiotherapy, antibiotics, virotherapy, polyadenosine diphosphate-ribose polymerase (PARP) inhibitors, and heat shock protein 90 (HSP90) inhibitors. The outcomes observed in both preclinical and clinical settings have been encouraging. Interestingly, manipulating gut microbiota via fecal microbiota transplantation (FMT) has been identified as a new strategy to increase the efficacy of immunotherapy in CRC patients. Therefore, integrating ICIs with other treatment approaches holds promise in enhancing the prognosis of CRC patients. This review focuses on the unmet need for new biomarkers to select patients for combination therapies and the ongoing work to overcome resistance and immune checkpoint blockade.}, }
@article {pmid40156349, year = {2025}, author = {Karataş, M and Bloemen, M and Cuypers, L and Wollants, E and Van Ranst, M and Matthijnssens, J}, title = {14 years of rotavirus A surveillance: unusual dominance of equine-like G3P[8] genotype with DS-1-like genotype constellation after the pandemic, Belgium, 2009 to 2023.}, journal = {Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin}, volume = {30}, number = {12}, pages = {}, pmid = {40156349}, issn = {1560-7917}, mesh = {*Rotavirus/genetics/isolation &amp; purification ; Humans ; *Rotavirus Infections/epidemiology/virology ; *Genotype ; Belgium/epidemiology ; Child, Preschool ; *Gastroenteritis/virology/epidemiology ; Infant ; *COVID-19/epidemiology/virology ; *Feces/virology ; *SARS-CoV-2/genetics ; Child ; Capsid Proteins/genetics ; Pandemics ; Male ; Female ; Antigens, Viral/genetics ; Animals ; Adolescent ; Infant, Newborn ; Rotavirus Vaccines/administration &amp; dosage ; Adult ; }, abstract = {IntroductionDespite vaccine availability, rotavirus persists as a leading cause of gastroenteritis in children younger than 5 years.AimWe aimed to evaluate temporal changes in rotavirus epidemiology in Belgium between 2009 and 2023, including the period of the COVID-19 pandemic.MethodsWe collected 8,024 rotavirus-positive stool samples throughout Belgium. For 6,352 samples, we determined the G and/or P genotypes through sequencing of the genes encoding the outer capsid proteins VP7 and VP4.ResultsBefore the COVID-19pandemic, we received on average 622 samples per rotavirus epidemiological year, which decreased to 114 and 111 samples during the two pandemic rotavirus epidemiological years, followed by a peak of 1,048 samples in the first post-pandemic year. Notably, the proportion of cases in the age group 2-5-years increased from 20.3% before to 33% after the pandemic (p < 0.001). Over the 14-year study period, the most common genotypes were G2P[4], G3P[8] and G9P[8]. Post-pandemic data show an unusually strong dominance of the equine-like G3P[8] genotype which carried a DS-1-like genotype constellation in the period 2021 to 2023. Additionally, vaccinated individuals were significantly overrepresented among patients infected with the equine-like VP7 carrying G3P[8] rotavirus compared with other genotypes, including typical human VP7 G3P[8].ConclusionDespite the presence of typical yearly genotype fluctuations, several epidemiological changes were associated with the COVID-19 pandemic, including the unusual dominance of an emerging rotavirus strain against which current vaccines may be less effective. It is essential to closely monitor this strain to determine if the phenomenon is temporary.}, }
@article {pmid40154780, year = {2025}, author = {Lin, SM and Le, PH and Chen, CL and Yeh, YM and Liao, HL and Chiu, CH}, title = {Faecal microbiota transplantation to decolonize vancomycin-resistant Enterococcus: A pilot study to evaluate safety and clinical outcome.}, journal = {Journal of global antimicrobial resistance}, volume = {43}, number = {}, pages = {1-6}, doi = {10.1016/j.jgar.2025.03.011}, pmid = {40154780}, issn = {2213-7173}, abstract = {OBJECTIVES: Faecal microbiota transplantation (FMT) has shown promise as a treatment for recurrent or refractory Clostridioides difficile infections. This study aimed to evaluate the decolonization effects of FMT on vancomycin-resistant Enterococcus (VRE).<br><br>METHODS: This feasibility trial prospectively recruited patients with more than three recurrent VRE infections. FMT was performed by infusing faecal microbiota solutions from healthy, unrelated donors into the participants' guts via colonoscopy. Faecal microbiota profiles before and after FMT were analysed.<br><br>RESULTS: Three of the six patients (50%) experienced VRE decolonization after FMT, lasting over 6 months. Baseline analysis revealed that patients who achieved decolonization had greater microbial diversity compared to those with persistent VRE colonization. Throughout the study, there were no adverse events observed in the patients after FMT. Elevated alpha diversity persisted in responders, while non-responders showed no significant changes. In responders, the abundance of genera within the phylum Firmicutes (Bacillota), including Anaerostipes, Blautia, Faecalibacterium, and Ruminococcus, and the genus Collinsella within the phylum Actinobacteriota increased steadily through 180 days post-FMT.<br><br>CONCLUSIONS: FMT may leverage bacterial strain competition to facilitate decolonization of drug-resistant organisms, with successful VRE decolonization potentially linked to increased abundance of phyla Firmicutes and Actinobacteriota over 6 months.}, }
@article {pmid40154488, year = {2025}, author = {Martin, D and Bonneau, M and Orfila, L and Horeau, M and Hazon, M and Demay, R and Lecommandeur, E and Boumpoutou, R and Guillotel, A and Guillemot, P and Croyal, M and Cressard, P and Cressard, C and Cuzol, A and Monbet, V and Derbré, F}, title = {Atypical gut microbial ecosystem from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen store in mice.}, journal = {Cell reports}, volume = {44}, number = {4}, pages = {115448}, doi = {10.1016/j.celrep.2025.115448}, pmid = {40154488}, issn = {2211-1247}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Humans ; *Glycogen/metabolism ; Mice ; *Insulin Resistance/physiology ; *Athletes ; Male ; Fecal Microbiota Transplantation ; *Muscle, Skeletal/metabolism ; *Exercise/physiology ; Adult ; Mice, Inbred C57BL ; Female ; Young Adult ; Feces/microbiology ; }, abstract = {Although the gut microbiota is known to act as a bridge between dietary nutrients and the body's energy needs, the interactions between the gut microbiota, host energy metabolism, and exercise capacity remain uncertain. Here, we characterized the gut microbiota ecosystem in a cohort of healthy normo-weight humans with highly heterogeneous aerobic exercise capacities and closely related body composition and food habits. While our data support the idea that the bacterial ecosystem appears to be modestly altered between individuals with low-to-high exercise capacities and close food habits, we report that gut bacterial α diversity, density, and functional richness are significantly reduced in athletes with very high exercise capacity. By using fecal microbiota transplantation, we report that the engraftment of gut microbiota from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen stores into transplanted mice, which highlights promising therapeutic perspectives in fecal transplantation from human donors selected based on exercise capacity traits.}, }
@article {pmid40153399, year = {2025}, author = {Gabarre, P and Palacios, R and Perez, K and Seksik, P and Bonnard, B and Loens, C and Lefranc, C and de Barros, JP and Anjou, L and Tamzali, Y and Zahr, N and Jaisser, F and Tourret, J}, title = {Immunosuppressive drugs and diet interact to modify the gut microbiota and cardiovascular risk factors, and to trigger diabetes.}, journal = {PloS one}, volume = {20}, number = {3}, pages = {e0320438}, pmid = {40153399}, issn = {1932-6203}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; Male ; Mice ; *Diet, High-Fat/adverse effects ; *Immunosuppressive Agents/pharmacology/adverse effects ; Mice, Inbred C57BL ; Diabetes Mellitus/microbiology ; Insulin Resistance ; Cardiometabolic Risk Factors ; Cardiovascular Diseases/etiology ; Feces/microbiology ; }, abstract = {BACKGROUND: Kidney transplant recipients are prescribed an immunosuppressive therapy (IST) and some of them follow a high fat diet (HFD) despite medical recommendations. Both are frequently associated with gut microbiota changes and metabolic disorders. We aimed at precisely identifying the effect of the IST and the HFD on metabolic parameters and the gut microbiota in mice, and at establishing correlations between the latters.<br><br>METHODS: 8-week-old male mice were treated with IST (a combination of prednisone, mycophenolate mofetil and tacrolimus) or not and were fed HFD or standard chow. Metabolic parameters were measured, and the gut microbiota was explored by the quantification of specific bacterial groups by qPCR and by 16S rDNA sequencing.<br><br>RESULTS: The HFD increased insulinemia and decreased the fecal proportion of Bacteroidetes and of Bacteroides. The IST increased systolic blood pressure and the fecal proportion of Escherichia coli. The HFD and the IST administered together resulted in an additive effect on glucose intolerance, high fasting blood glucose, homeostasis model assessment of insulin resistance (HOMA-IR), percentage of fat mass, blood triglyceride, blood cholesterol, and endotoxemia. On the opposite, the HFD and the IST had antagonistic effects on body weight, the proportion of Firmicutes, the Firmicutes/Bacteroidetes ratio, and the proportion of Clostridium leptum, Bifidobacterium, and Lactobacillus in the feces. Finally, we found that the correlations between gut bacterial communities and metabolic consequences of the HFD were altered by the IST.<br><br>CONCLUSION: The IST and the HFD have specific consequences on the gut microbiota and metabolism. We hypothesize that the metabolic consequences are at least partially mediated by IST/HFD-induced dysbiosis.}, }
@article {pmid40151642, year = {2025}, author = {Cai, X and Cho, JY and Chen, L and Liu, Y and Ji, F and Salgado, K and Ge, S and Yang, D and Yu, H and Shao, J and Futreal, PA and Sepesi, B and Gibbons, D and Chen, Y and Wang, G and Cheng, C and Wu, M and Zhang, J and Hsiao, A and Xia, T}, title = {Enriched pathways in gut microbiome predict response to immune checkpoint inhibitor treatment across demographic regions and various cancer types.}, journal = {iScience}, volume = {28}, number = {4}, pages = {112162}, pmid = {40151642}, issn = {2589-0042}, abstract = {Understanding the effect of gut microbiota function on immune checkpoint inhibitor (ICI) responses is urgently needed. Here, we integrated 821 fecal metagenomes from 12 datasets to identify differentially abundant genes and construct random forest models to predict ICI response. Gene markers demonstrated excellent predictive performance, with an average area under the curve (AUC) of 0.810. Pathway analyses revealed that quorum sensing (QS), ABC transporters, flagellar assembly, and amino acid biosynthesis pathways were enriched between responders (R) and non-responders (NRs) across 12 datasets. Furthermore, luxS, manA, fliC, and trpB exhibited consistent changes between R and NR across 12 datasets. Follow-up microbiota transplant experiments showed that inter-species signaling by different QS autoinducer-2 (AI-2) molecules (synthesized by luxS) can act on overall community function to promote the colonization of Akkermansia muciniphila, which is associated with superior ICI responses. Together, our data highlight the role of gut microbiota function in modulating the microbiome and antitumor immunity.}, }
@article {pmid40150325, year = {2025}, author = {Wang, K and Suo, Y and Shen, D and Shi, Y and Jin, X and Li, Y and Li, C}, title = {Improvement in Heat Stress-Induced Damage to Sperm Quality Following Fecal Microbiota Transplantation from L-Arginine-Treated Mice.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {6}, pages = {}, pmid = {40150325}, issn = {2076-2615}, support = {32372935//National Natural Science Foundation of China/ ; }, abstract = {Heat stress has become a significant concern in animal husbandry, as it adversely affects reproductive performance, particularly sperm quality, through mechanisms that are not fully understood. This study aimed to investigate the protective effects of L-arginine against heat stress-induced sperm damage and explore its potential mechanisms through the modulation of the intestinal microbiota. This study consisted of two experiments. First, in a heat-stressed mouse model, L-arginine was administered to evaluate its effects on the reproductive health of heat-stressed mice. In the second experiment, by transplanting L-arginine-induced changes in the gut microbiota into heat-stressed mice, the protective effects of the microbiota on the sperm of heat-stressed mice were assessed. The findings revealed a significant amelioration of decreased sperm quality and testicular injury induced by heat stress. Post heat stress, mice supplemented with L-arginine presented an increase in seminal vesicle gland weight and index, partial alleviation of testicular tissue morphology, and a substantial increase in testosterone concentration (p < 0.05). Additionally, L-arginine upregulated the expression of testosterone synthesis genes and the mRNA levels of sperm generation-related genes, including 3β-HSD, Stra8, WT1, and Gdnf (p < 0.05). Concurrently, L-arginine-induced microbial communities mitigated heat stress-induced decreases in sperm quality and testicular injury, coupled with increases in the mRNA expression levels of Cyp17a1, 17β-HSD, Plzf, and Gdnf (p < 0.05). Furthermore, there was a reduction in the expression of proinflammatory factors, namely, NFκB, MyD88, TNF-α, and TGF-β3 (p < 0.05). In conclusion, L-arginine may influence the ratio of beneficial bacteria to harmful bacteria in the intestinal microbiota, thereby reducing inflammation caused by heat stress, maintaining intestinal health, and influencing the microenvironment for spermatogenesis.}, }
@article {pmid40149692, year = {2025}, author = {Sivakumar, N and Krishnamoorthy, A and Ryali, H and Arasaradnam, RP}, title = {Gut Microbial Targets in Inflammatory Bowel Disease: Current Position and Future Developments.}, journal = {Biomedicines}, volume = {13}, number = {3}, pages = {}, pmid = {40149692}, issn = {2227-9059}, abstract = {Inflammatory bowel disease (IBD) is a debilitating condition in which surgery is often seen as a last resort. However, this is associated with morbidity and, in some cases, mortality. There are emerging therapies that seek to better modulate the immune response of hosts with IBD. Aims: The main aim of this study is to focus on novel therapies and techniques studied in the last year that are non-surgical treatments of IBD. Methods: We looked at all the research between March 2024 and February 2025 detailing treatment in IBD and focused on the gut microbiome and gene therapy. Results: Novel therapies are gaining traction in safety and popularity. The results from some animal studies show promise and, with FDA approval, some probiotic therapies show optimistic research potential for future human trials. Conclusions: The research into the diagnostics and novel therapies available on the horizon for humans is very promising. Animal studies have shown potentially transferrable and safe therapies that can target specific sites of inflammation. Modulating the inflammatory response is a powerful therapy with what is shown to be a reasonably safe profile to build further research on.}, }
@article {pmid40149377, year = {2025}, author = {Zhang, B and Mohd Sahardi, NFN and Di, W and Long, X and Shafiee, MN}, title = {The Gut-Endometrium Axis: Exploring the Role of Microbiome in the Pathogenesis and Treatment of Endometrial Cancer-A Narrative Review.}, journal = {Cancers}, volume = {17}, number = {6}, pages = {}, pmid = {40149377}, issn = {2072-6694}, abstract = {Background/Objectives: Endometrial cancer (EC) is a prevalent gynecological malignancy with an increasing incidence, particularly in developed countries. Recent research has demonstrated the significant involvement of gut and endometrial microbiomes in the pathogenesis and progression of EC. This review provides a comprehensive overview of the existing knowledge on the interactions between these microbial communities and their influence on EC. Methodology: A literature review was conducted using electronic databases including Google Scholar, Scopus, and PUBMED, covering the period from 2017 to 2024. The following keywords were used for the literature search: (1) gut microbiome and endometrial cancer, (2) endometrium microbiome and endometrial cancer, and (3) endometrial cancer and microbial dysbiosis. The selected articles were chosen based on inclusion and exclusion criteria. Scale for Assessment of Narrative Review Articles (SANRA) was used for evaluating and assessing the quality of articles. Results: The gut microbiome modulates systemic inflammation, immune responses, and estrogen metabolism, all of which are crucial factors in EC development. Dysbiosis is an imbalance in the composition of microbes that can cause chronic inflammation and hormonal imbalances, which can contribute to the EC. Similarly, the endometrial microbiome, while less extensively studied, has been implicated in EC through mechanisms involving local immune modulation and the production of harmful metabolites. Probiotics, prebiotics, fecal microbiota transplantation (FMT), and personalized microbiota-based therapies can be used as clinical interventions for EC management. This review emphasizes the need for further research to explore the gut-endometrium axis and its potential for innovative therapeutic approaches. Understanding these complex interactions will become a novel strategy to prevent and treat EC, ultimately enhancing patient outcomes.}, }
@article {pmid40149075, year = {2025}, author = {Kenneth, MJ and Wu, CC and Fang, CY and Hsu, TK and Lin, IC and Huang, SW and Chiu, YC and Hsu, BM}, title = {Exploring the Impact of Chemotherapy on the Emergence of Antibiotic Resistance in the Gut Microbiota of Colorectal Cancer Patients.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {3}, pages = {}, pmid = {40149075}, issn = {2079-6382}, support = {R0010//This research was supported by Cheng Hsin General Hospital, Dalin Tzu Chi Hospital, Asia University Hospital, and Ditmanson Medical Foundation Chiayi Christian Hospital-National Chung Cheng University Joint Research Program/ ; }, abstract = {With nearly half of colorectal cancer (CRC) patients diagnosed at advanced stages where surgery alone is insufficient, chemotherapy remains a cornerstone for this cancer treatment. To prevent infections and improve outcomes, antibiotics are often co-administered. However, chemotherapeutic interactions with the gut microbiota cause significant non-selective toxicity, affecting not only tumor and normal epithelial cells but also the gut microbiota. This toxicity triggers the bacterial SOS response and loss of microbial diversity, leading to bacterial mutations and dysbiosis. Consequently, pathogenic overgrowth and systemic infections increase, necessitating broad-spectrum antibiotics intervention. This review underscores how prolonged antibiotic use during chemotherapy, combined with chemotherapy-induced bacterial mutations, creates selective pressures that drive de novo antimicrobial resistance (AMR), allowing resistant bacteria to dominate the gut. This compromises the treatment efficacy and elevates the mortality risk. Restoring gut microbial diversity may mitigate chemotherapy-induced toxicity and improve therapeutic outcomes, and emerging strategies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, show considerable promise. Given the global threat posed by antibiotic resistance to cancer treatment, prioritizing antimicrobial stewardship is essential for optimizing antibiotic use and preventing resistance in CRC patients undergoing chemotherapy. Future research should aim to minimize chemotherapy's impact on the gut microbiota and develop targeted interventions to restore microbial diversity affected during chemotherapy.}, }
@article {pmid40147837, year = {2025}, author = {Foroutan, F and Vandvik, PO and Helsingen, LM and Kalager, M and Rutter, M and Selby, K and Pilonis, ND and Anderson, JC and McKinnon, A and Fuchs, JM and Quinlan, C and Buskermolen, M and Senore, C and Wang, P and Sung, JJY and Haug, U and Bjerkelund, S and Triantafyllou, K and Shung, DL and Halvorsen, N and McGinn, T and Hafver, TL and Reinthaler, V and Guyatt, G and Agoritsas, T and Sultan, S}, title = {Computer aided detection and diagnosis of polyps in adult patients undergoing colonoscopy: a living clinical practice guideline.}, journal = {BMJ (Clinical research ed.)}, volume = {388}, number = {}, pages = {e082656}, doi = {10.1136/bmj-2024-082656}, pmid = {40147837}, issn = {1756-1833}, mesh = {Humans ; *Colonoscopy/adverse effects/standards/methods ; *Colorectal Neoplasms/diagnosis ; *Colonic Polyps/diagnosis ; *Diagnosis, Computer-Assisted/methods ; Middle Aged ; Aged ; Adult ; Early Detection of Cancer/methods ; Artificial Intelligence ; }, abstract = {CLINICAL QUESTION: In adult patients undergoing colonoscopy for any indication (screening, surveillance, follow-up of positive faecal immunochemical testing, or gastrointestinal symptoms such as blood in the stools) what are the benefits and harms of computer-aided detection (CADe)?<br><br>CONTEXT AND CURRENT PRACTICE: Colorectal cancer (CRC), the third most common cancer and the second leading cause of cancer-related death globally, typically arises from adenomatous polyps. Detection and removal of polyps during colonoscopy can reduce the risk of cancer. CADe systems use artificial intelligence (AI) to assist endoscopists by analysing real-time colonoscopy images to detect potential polyps. Despite their increasing use in clinical practice, guideline recommendations that carefully balance all patient-important outcomes remain unavailable. In this first iteration of a living guideline, we address the use of CADe at the level of an individual patient.<br><br>EVIDENCE: Evidence for this recommendation is drawn from a living systematic review of 44 randomised controlled trials (RCTs) involving more than 30&#x2009;000 participants and a companion microsimulation study simulating 10 year follow-up for 100&#x2009;000 individuals aged 60-69 years to assess the impact of CADe on patient-important outcomes. While no direct evidence was found for critical outcomes of colorectal cancer incidence and post-colonoscopy cancer incidence, low certainty data from the trials indicate that CADe may increase positive endoscopy findings. The microsimulation modelling, however, suggests little to no effect on CRC incidence, CRC-related mortality, or colonoscopy-related complications (perforation and bleeding) over the 10 year follow-up period, although low certainty evidence indicates CADe may increase the number of colonoscopies performed per patient. A review of values and preferences identified that patients value mortality reduction and quality of care but worry about increased anxiety, overdiagnosis, and more frequent surveillance.<br><br>RECOMMENDATION: For adults who have agreed to undergo colonoscopy, we suggest against the routine use of CADe (weak recommendation).<br><br>An international panel, including three patient partners, 11 healthcare providers, and seven methodologists, deemed by MAGIC and The BMJ to have no relevant competing interests, developed this recommendation. For this guideline the panel took an individual patient approach. The panel started by defining the clinical question in PICO format, and prioritised outcomes including CRC incidence and mortality. Based on the linked systematic review and microsimulation study, the panel sought to balance the benefits, harms, and burdens of CADe and assumed patient preferences when making this recommendation UNDERSTANDING THE RECOMMENDATION: The guideline panel found the benefits of CADe on critical outcomes, such as CRC incidence and post-colonoscopy cancer incidence, over a 10 year follow up period to be highly uncertain. Low certainty evidence suggests little to no impact on CRC-related mortality, while the potential burdens-including more frequent surveillance colonoscopies-are likely to affect many patients. Given the small and uncertain benefits and the likelihood of burdens, the panel issued a weak recommendation against routine CADe use.The panel acknowledges the anticipated variability in values and preferences among patients and clinicians when considering these uncertain benefits and potential burdens. In healthcare settings where CADe is available, individual decision making may be appropriate.<br><br>UPDATES: This is the first iteration of a living practice guideline. The panel will update this living guideline if ongoing evidence surveillance identifies new CADe trial data that substantially alters our conclusions about CRC incidence, mortality, or burdens, or studies that increase our certainty in values and preferences of individual patients. Updates will provide recommendations on the use of CADe from a healthcare systems perspective (including resource use, acceptability, feasibility, and equity), as well as the combined use of CADe and computer aided diagnosis (CADx). Users can access the latest guideline version and supporting evidence on MAGICapp, with updates periodically published in The BMJ.}, }
@article {pmid40147263, year = {2025}, author = {Ye, X and An, X and Zhang, T and Kong, Y and Jia, S and Wu, J}, title = {CGA protects against experimental colitis by modulating host purine metabolism through the gut microbiota.}, journal = {International immunopharmacology}, volume = {153}, number = {}, pages = {114547}, doi = {10.1016/j.intimp.2025.114547}, pmid = {40147263}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis/chemically induced/drug therapy/microbiology/metabolism ; *Purines/metabolism ; Dextran Sulfate ; *Chlorogenic Acid/therapeutic use/pharmacology ; Mice ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Colon/pathology/drug effects/microbiology ; Fecal Microbiota Transplantation ; Cytokines/metabolism ; Dysbiosis/drug therapy ; Humans ; Intestinal Mucosa/drug effects/pathology ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Fatty Acids, Volatile/metabolism ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVE: Alterations in the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Chlorogenic acid (CGA), a product of the esterification of caffeic acid and quinic acid, is one of the most abundant polyphenols in the human diet and has potential beneficial effects on gut function. However, the underlying mechanisms remain unclear. In this study, the pharmacological effects of CGA on colitis and the potential underlying mechanisms were investigated.<br><br>METHODS: A mouse model of colitis was induced via the use of 4&#xa0;% dextran sulfate sodium (DSS), and the mice were treated with 200&#xa0;mg/kg CGA. Body weight, colon length, colon tissue pathology, and plasma and colon inflammatory cytokine levels were assessed. RNA sequencing was used to detect changes in gene expression in mouse colon tissues, and 16S rRNA sequencing was used to analyze the composition and structure of the gut microbiota. Fecal metabolomic analysis was performed, and fecal microbiota transplantation (FMT) was used to evaluate the contribution of the gut microbiota.<br><br>RESULTS: CGA significantly alleviated DSS-induced colitis, alleviating intestinal mucosal barrier damage and gut microbiota dysbiosis. It significantly enriched bacteria that produce short-chain fatty acids (SCFAs). CGA inhibited the accumulation of purine metabolites derived from the microbiota and suppressed immune-related signaling cascades, exerting immunomodulatory effects. Furthermore, the gut microbiota of CGA-treated mice alleviated DSS-induced colitis through FMT.<br><br>CONCLUSION: CGA alleviates colitis in a gut microbiota-dependent manner, potentially providing a new strategy for the treatment of IBD.}, }
@article {pmid40143866, year = {2025}, author = {Zhou, M and Niu, B and Ma, J and Ge, Y and Han, Y and Wu, W and Yue, C}, title = {Intervention and research progress of gut microbiota-immune-nervous system in autism spectrum disorders among students.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1535455}, pmid = {40143866}, issn = {1664-302X}, abstract = {Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social interaction and communication, repetitive and stereotyped behaviors, restricted interests, and sensory abnormalities. Its etiology is influenced by both genetic and environmental factors, with no definitive cause identified and no specific pharmacological treatments available, posing a significant burden on patients' families and society. In recent years, research has discovered that gut microbiota dysbiosis plays a crucial role in the pathogenesis of ASD. The gut microbiota can influence brain function and behavior through the gut-brain axis via the nervous system, immune system, and metabolic pathways. On the one hand, specific gut microbes such as Clostridium and Prevotella species are found to be abnormal in ASD patients, and their metabolic products, like short-chain fatty acids, serotonin, and GABA, are also involved in the pathological process of ASD. On the other hand, ASD patients exhibit immune system dysfunction, with gut immune cells and related cytokines affecting neural activities in the brain. Currently, intervention methods targeting the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, have shown some potential in improving ASD symptoms. However, more studies are needed to explore their long-term effects and optimal treatment protocols. This paper reviews the mechanisms and interrelationships among gut microbiota, immune system, and nervous system in ASD and discusses the challenges and future directions of existing research, aiming to provide new insights for the prevention and treatment of ASD.}, }
@article {pmid40143713, year = {2025}, author = {Zhang, F and Kamm, MA and Wu, X and Kao, D and Borody, TJ and Chen, LA and He, X and Fischer, M and Wong, SH and Ng, SC and Cui, B and Chan, FK and Nie, Y and Sood, A and Li, J and Sun, Y and Dai, I and Chen, Q and Lv, M and Zhang, Z and Ianiro, G and Yang, Y and Kelly, CR}, title = {Preferred Reporting Items for Microbiotherapy (PRIM) Guidelines Across Medical Disciplines: An International Delphi Consensus.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16947}, pmid = {40143713}, issn = {1440-1746}, support = {2021YFA0717004//Ministry of Science and Technology of China, National Key Program/ ; 82170563//National Natural Science Fundation of China/ ; 2020-3HIM//Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; }, abstract = {Microbiotherapy has opened new avenues for managing dysbiosis-related diseases. However, many studies did not cover all the necessary reporting items for microbiotherapy making the interpretation of results, safety assessment, technology extension, and even the transparency of legitimacy difficult. This project consisted of 2 phases. First, we proposed an initial preferred reporting items for microbiotherapy (PRIM) checklist and applied it to oncology studies from 2011 to 2023 according to Meta-Analyses guideline. Only 39.3% (n = 64) of these studies (n = 163) met all PRIM checklist items. The culture-based microbiotherapy (CMT) studies had higher score than non-culture-based (NMT) ones (p = 0.018). In the second phase, the expert panel consisting of 22 specialists from eight countries across Asia, Australia, Europe, and North America refined and finalized the PRIM guidelines (named as PRIM 2024) through Delphi consensus. The PRIM 2024 guidelines conclude 10 statements and 18 points on diagnosis, delivery route, source, classification, preparation, dosage, state, concomitant treatment, efficacy, and safety. The panel defined less than 80% of all PRIM points (14 points) as low-quality reports. These guidelines are recommended for reporting on microbiotherapy in clinical studies and reports on compassionate use, including but not limited to fecal microbiota transplantation, phage therapy, probiotics, and synbiotics. These consistent and transparent reporting items can help researchers and practitioners better evaluate, compare, implement research findings in microbiotherapy.}, }
@article {pmid40142532, year = {2025}, author = {Niu, Q and Yang, K and Zhou, Z and Huang, Q and Wang, J}, title = {Intergenerational Transmission of Gut Microbiome from Infected and Non-Infected Salmonella pullorum Hens.}, journal = {Microorganisms}, volume = {13}, number = {3}, pages = {}, pmid = {40142532}, issn = {2076-2607}, support = {2022-02-08-00-12-F01184//Shanghai Agriculture Applied Technology Development Program,China/ ; }, abstract = {Pullorum disease (PD) is one of the common infectious diseases in the poultry industry in the world. Our previous study showed that gut bacterial structure has a significant difference between positive and negative hens. However, the gut bacterial basis of intergenerational transmission of PD continues to elude a scientific explanation. The present study carried out fecal microbiota transplantation (FMT) in chicks of a negative group, then fecal samples of the chicks in the control team (CT), Salmonella pullorum (S. pullorum)-negative transplantation team (PN) and S. pullorum-positive transplantation team (PP) were separately collected to be analyzed for microbial structure and prediction functions. Microbial diversity results revealed that there was a large difference in the gut microbiota of these three groups. Prevotella and Parasutterella with higher abundance in PN (p < 0.05) were transplanted from gut bacteria of S. pullorum-negative hens. Furthermore, the differences of the most major microbial functions (top 100) were similar in hens and chicks, including a pentose phosphate pathway and oxidative phosphorylation. The data provided a reference for exploring the intergenerational transmission and genetic mechanisms of gut microbiota associated with S. pullorum in poultry, as well as a theoretical basis for improving intestinal health through the rational regulation of microbiota-host interactions.}, }
@article {pmid40142480, year = {2025}, author = {Shaheen, M and McDougall, C and Chan, L and Franz, R and Wong, K and Giebelhaus, RT and Nguyen, G and Nam, SL and de la Mata, AP and Yeo, S and Harynuk, JJ and Pakpour, S and Xu, H and Kao, D}, title = {Impact of Fecal Microbiota Transplant Formulations, Storage Conditions, and Duration on Bacterial Viability, Functionality, and Clinical Outcomes in Patients with Recurrent Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {13}, number = {3}, pages = {}, pmid = {40142480}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is the most effective therapy for preventing recurrent Clostridioides difficile infection (rCDI). However, the impact of FMT formulations and storage conditions on bacterial viability, community structure, functionality, and clinical efficacy remains under-investigated. We studied the effect of different storage conditions on the bacterial viability (live/dead staining and cell sorting), community structure (16S rDNA analysis), and metabolic functionality (fermentation) of frozen and lyophilized FMT formulations. The clinical success rates of rCDI patients were correlated retrospectively with FMT formulations, storage durations, and host factors using the Edmonton FMT program database. Bacterial viability remained at 10-20% across various storage conditions and formulations and was comparable to that of fresh FMT. Live and dead bacterial fractions in both frozen and lyophilized FMT preparations exhibited distinct community structures. Storage durations, but not temperatures, negatively affected bacterial diversity. More short-chain fatty acids were found in the metabolomic profiling of in vitro fermentation products using lyophilized than frozen FMT. Clinical success rates in 537 rCDI patients receiving a single dose of FMT were not significantly different among the three formulations. However, longer storage durations and advanced recipient age negatively impacted clinical efficacy. Together, our findings suggest that FMT formulations and storage durations should be considered when establishing guidelines for product shelf life for optimal treatment outcomes.}, }
@article {pmid40142449, year = {2025}, author = {Kume, M and Din, J and Zegarra-Ruiz, DF}, title = {Dysregulated Intestinal Host-Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models.}, journal = {Microorganisms}, volume = {13}, number = {3}, pages = {}, pmid = {40142449}, issn = {2076-2607}, abstract = {Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. Additionally, intestinal barrier impairment is thought to contribute to the ability of pathobionts to evade and breach immune defenses, resulting in antigen cross-reactivity, microbial translocation, subsequent immune activation, and, ultimately, multiple organ failure. Since the detailed mechanisms underlying these processes are difficult to examine using human samples, murine models are crucial. Various SLE murine models, including genetically modified spontaneous and inducible murine models, offer insights into pathobionts and how they dysregulate systemic immune systems. Furthermore, since microbial metabolites modulate systemic immune responses, bacteria and their metabolites can be targeted for treatment. Based on human and mouse research insights, this review examines how lupus pathobionts trigger intestinal and systemic immune dysregulation. Therapeutic approaches, such as fecal microbiota transplantation and dietary adjustments, show potential as cost-effective and safe methods for preventing and treating SLE. Understanding the complex interactions between the microbiota, host factors, and immune dysregulation is essential for developing novel, personalized therapies to tackle this multifaceted disease.}, }
@article {pmid40141109, year = {2025}, author = {Ye, Y and Abulizi, A and Zhang, Y and Lu, F and An, Y and Ren, C and Zhang, H and Wang, Y and Lin, D and Lu, D and Li, M and Yang, B}, title = {Ganoderic Acid Ameliorates Ulcerative Colitis by Improving Intestinal Barrier Function via Gut Microbiota Modulation.}, journal = {International journal of molecular sciences}, volume = {26}, number = {6}, pages = {}, pmid = {40141109}, issn = {1422-0067}, support = {82273999//National Natural Science Foundation of China grants/ ; 81974083//National Natural Science Foundation of China grants/ ; 7212151//Beijing Natural Science Foundation grant/ ; 2022-JKCS-15//The grant from the non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/microbiology/chemically induced/metabolism ; Mice ; *Triterpenes/pharmacology ; *Intestinal Mucosa/metabolism/drug effects/microbiology/pathology ; *Dextran Sulfate/adverse effects ; Male ; Disease Models, Animal ; Humans ; Zonula Occludens-1 Protein/metabolism/genetics ; Colon/drug effects/metabolism/pathology/microbiology ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Intestinal Barrier Function ; }, abstract = {Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal disease that affects millions of humans worldwide and imposes a huge social and economic burden. It is necessary to find safe and efficient drugs for preventing and treating UC. The aim of this study was to determine whether ganoderic acid (GA), the main bioactive components of Ganoderma lucidum, has preventive and therapeutic effect on UC in a dextran sulfate sodium (DSS)-induced UC mouse model. Our experimental results showed that GA significantly ameliorated the body weight loss and disease activity index (DAI) of UC mice. GA significantly restored 11% of the colon length and 69% of the spleen index compared to UC mice. GA significantly decreased the intestinal inflammatory response and improved the barrier function of the intestine by upregulating the tight junction proteins Zonula occludens-1 (ZO-1), occludin and claudin-1. A co-housing experiment showed that gut microbiota accounted for the therapeutic activity of GA on UC, which was confirmed by fecal microbiota transplantation from GA-treated mice to the UC mice. Furthermore, 16S rDNA high-throughput sequencing of fecal bacteria showed that GA significantly enriched the abundance of Lactobacillus, Oscillospira, Odoribacter and Ruminococcus, which were positively correlated with colon length. Furthermore, this study found the functional metabolites, including Indole-3-acetaldehyde (IAAld), Glutamine (Gln) and Glutathione (GSH), reduced barrier damage in the Caco-2 cell model. In conclusion, this study suggests that GA could ameliorate UC by improving intestinal barrier function via modulating gut microbiota and associated metabolites.}, }
@article {pmid40141007, year = {2025}, author = {Wang, Y and Chen, Y and Xiao, Z and Shi, Y and Fu, C and Cao, Y}, title = {Fecal microbiota transplantation modulates myeloid-derived suppressor cells and attenuates renal fibrosis in a murine model.}, journal = {Renal failure}, volume = {47}, number = {1}, pages = {2480749}, pmid = {40141007}, issn = {1525-6049}, mesh = {Animals ; *Myeloid-Derived Suppressor Cells/metabolism/immunology ; *Fecal Microbiota Transplantation ; *Mice, Inbred C57BL ; Mice ; *Disease Models, Animal ; *Fibrosis ; *Kidney/pathology ; *Renal Insufficiency, Chronic/therapy/microbiology ; Male ; Cytokines/metabolism ; Gastrointestinal Microbiome ; Ureteral Obstruction/complications/therapy ; Dysbiosis/therapy/complications ; }, abstract = {BACKGROUND: Renal fibrosis is a hallmark of progressive chronic kidney disease (CKD), with emerging evidence linking gut microbiota dysbiosis to disease progression. Myeloid-derived suppressor cells (MDSCs) have demonstrated renoprotective effects, yet the impact of fecal microbiota transplantation (FMT) on MDSC-mediated modulation of renal fibrosis remains unclear.<br><br>METHODS: C57BL/6J mice underwent unilateral ureteral obstruction (UUO) to induce renal fibrosis, followed by FMT administration via gavage. Flow cytometry was used to quantify granulocytic (G-MDSCs) and monocytic (M-MDSCs) MDSC populations in peripheral blood, kidney, and spleen. To elucidate the role of MDSCs in FMT-mediated effects, MDSCs were depleted or adoptively transferred in vivo. Renal fibrosis severity and inflammatory cytokine expression were subsequently analyzed.<br><br>RESULTS: FMT altered MDSC distribution, increasing M-MDSC accumulation in the blood and kidney. This was associated with downregulation of proinflammatory cytokines and attenuation of renal fibrosis. Adoptive MDSC transfer similarly produced anti-inflammatory and antifibrotic effects, reinforcing their therapeutic role in FMT-mediated renal protection.<br><br>CONCLUSIONS: FMT enhances M-MDSC-mediated immunomodulation, reducing inflammation and renal fibrosis in UUO-induced CKD. These findings suggest a potential therapeutic strategy targeting the gut-kidney axis in CKD management.}, }
@article {pmid40140901, year = {2025}, author = {Wu, Y and Cheng, R and Lin, H and Li, L and Jia, Y and Philips, A and Zuo, T and Zhang, H}, title = {Gut virome and its implications in the pathogenesis and therapeutics of inflammatory bowel disease.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {183}, pmid = {40140901}, issn = {1741-7015}, support = {2023YFS0279//Sichuan Science and Technology Program/ ; }, mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/microbiology/virology ; *Virome ; *Gastrointestinal Microbiome ; }, abstract = {Inflammatory bowel disease (IBD) refers to chronic, recurrent inflammatory intestinal disorders, primarily including Crohn's disease (CD) and Ulcerative colitis (UC). Numerous studies have elucidated the importance of the gut microbiome in IBD. Recently, numerous studies have focused on the gut virome, an intriguing and enigmatic aspect of the gut microbiome. Alterations in the composition of phages, eukaryotic viruses, and human endogenous retroviruses that occur in IBD suggest potential involvement of the gut virome in IBD. Nevertheless, the mechanisms by which it maintains intestinal homeostasis and interacts with diseases are only beginning to be understood. Here, we thoroughly reviewed the composition of the gut virome in both healthy individuals and IBD patients, emphasizing the key viruses implicated in the onset and progression of IBD. Furthermore, the complex connections between the gut virome and the intestinal barrier, immunity, and gut microbiome were dissected to advance the interpretation of IBD pathogenesis. The updated discussion of the evidence regarding the gut virome will advance our knowledge in gut virome and chronic gastrointestinal diseases. Targeting the gut virome is a promising avenue for IBD treatment in future.}, }
@article {pmid40138872, year = {2025}, author = {Liang, T and Jiang, T and Liang, Z and Li, L and Chen, Y and Chen, T and Yang, L and Zhang, N and Dong, B and Xie, X and Gu, B and Wu, Q}, title = {Gut microbiota-driven BCAA biosynthesis via Staphylococcus aureus -expressed acetolactate synthase impairs glycemic control in type 2 diabetes in South China.}, journal = {Microbiological research}, volume = {296}, number = {}, pages = {128145}, doi = {10.1016/j.micres.2025.128145}, pmid = {40138872}, issn = {1618-0623}, mesh = {*Diabetes Mellitus, Type 2/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; *Staphylococcus aureus/enzymology/genetics/metabolism ; *Amino Acids, Branched-Chain/biosynthesis ; *Acetolactate Synthase/metabolism/genetics ; Humans ; Animals ; Mice ; China ; Male ; Insulin Resistance ; Female ; Middle Aged ; *Glycemic Control ; Blood Glucose ; Feces/microbiology ; Staphylococcal Infections/microbiology ; Metagenomics ; Prediabetic State/microbiology ; Metabolomics ; Insulin ; }, abstract = {An increase in branched-chain amino acid (BCAA) levels can result in insulin resistance at different stages of type 2 diabetes (T2D), however, the causes of this increase are unclear. We performed metagenomics and metabolomics profiling in patients with prediabetes (PDM), newly diagnosed diabetes (NDDM), and post-medication type 2 diabetes (P2DM) to investigate whether altered gut microbes and metabolites could explain the specific clinical characteristics of different disease stages of T2D. Here we identify acetolactate synthase (ALS) a BCAA biosynthesis enzyme in Staphylococcus aureus as a cause of T2D insulin resistance. Compared with healthy peoples, patients with PDM, NDDM, and P2DM groups, especially in P2DM group, have increased faecal numbers of S. aureus. We also demonstrated that insulin administration may be a risk factor for S. aureus infection in T2D. The presence of ALS-positive S. aureus correlated with the levels of BCAAs and was associated with an increased fasting blood glucose (FBG) and insulin resistance. Humanized microbiota transplantation experiment indicated that ALS contributes to disordered insulin resistance mediated by S. aureus. We also found that S. aureus phage can reduced the FBG levels and insulin resistance in db/db mice. The ALS-positive S. aureus are associated with insulin resistance in T2D, opening a new therapeutic avenue for the prevention or treatment of diabetes.}, }
@article {pmid40137411, year = {2025}, author = {Mougiou, D and Gioula, G and Skoura, L and Anastassopoulou, C and Kachrimanidou, M}, title = {Insights into the Interaction Between Clostridioides difficile and the Gut Microbiome.}, journal = {Journal of personalized medicine}, volume = {15}, number = {3}, pages = {}, pmid = {40137411}, issn = {2075-4426}, abstract = {Clostridioides difficile (C. difficile) is a significant healthcare-associated pathogen that is predominantly caused by antibiotic-induced microbiota disturbance. Antibiotics decrease microbial diversity, resulting in C. difficile colonization and infection. Clostridium difficile infection (CDI) manifests through toxins A and B, causing diarrhea and colitis. Antibiotic usage, old age, and hospitalization are significant risk factors. A healthy gut microbiota, which is dominated by Firmicutes and Bacteroidetes, provides colonization resistance to C. difficile due to competition for nutrients, creating inhibitory substances and stimulating the immune response. Antibiotic-induced dysbiosis decreases resistance, allowing C. difficile spores to transform into vegetative forms. Patients with CDI have decreased gut microbiota diversity, with a decrease in beneficial bacteria, including Bacteroidetes, Prevotella, and Bifidobacterium, and a rise in harmful bacteria like Clostridioides and Lactobacillus. This disparity worsens the infection's symptoms and complicates therapy. Fecal Microbiota Transplantation (FMT) has emerged as a potential therapy for recurrent CDI by restoring gut microbiota diversity and function. Comprehending the connection between gut microbiota and CDI pathogenesis is critical for establishing effective preventive and treatment plans. Maintaining a healthy gut microbiota through careful antibiotic use and therapeutic options such as FMT can help in the management and prevention of CDI.}, }
@article {pmid40136508, year = {2025}, author = {Zalila-Kolsi, I and Dhieb, D and Osman, HA and Mekideche, H}, title = {The Gut Microbiota and Colorectal Cancer: Understanding the Link and Exploring Therapeutic Interventions.}, journal = {Biology}, volume = {14}, number = {3}, pages = {}, pmid = {40136508}, issn = {2079-7737}, abstract = {CRC remains a significant public health challenge due to its high prevalence and mortality rates. Emerging evidence highlights the critical role of the gut microbiota in both the pathogenesis of CRC and the efficacy of treatment strategies, including chemotherapy and immunotherapy. Dysbiosis, characterized by imbalances in microbial communities, has been implicated in CRC progression and therapeutic outcomes. This review examines the intricate relationship between gut microbiota composition and CRC, emphasizing the potential for microbial profiles to serve as biomarkers for early detection and prognosis. Various interventions, such as prebiotics, probiotics, postbiotics, fecal microbiota transplantation, and dietary modifications, aim to restore microbiota balance and shift dysbiosis toward eubiosis, thereby improving health outcomes. Additionally, the integration of microbial profiling into clinical practice could enhance diagnostic capabilities and personalize treatment strategies, advancing the field of oncology. The study of intratumoral microbiota offers new diagnostic and prognostic tools that, combined with artificial intelligence algorithms, could predict treatment responses and assess the risk of adverse effects. Given the growing understanding of the gut microbiome-cancer axis, developing microbiota-oriented strategies for CRC prevention and treatment holds promise for improving patient care and clinical outcomes.}, }
@article {pmid40134274, year = {2025}, author = {Flores-Treviño, S and Bocanegra-Ibarias, P and Salas-Treviño, D and Ramírez-Elizondo, MT and Pérez-Alba, E and Camacho-Ortiz, A}, title = {Microbiota transplantation and administration of live biotherapeutic products for the treatment of dysbiosis-associated diseases.}, journal = {Expert opinion on biological therapy}, volume = {25}, number = {5}, pages = {1-14}, doi = {10.1080/14712598.2025.2484303}, pmid = {40134274}, issn = {1744-7682}, mesh = {Humans ; *Dysbiosis/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Biological Products/therapeutic use/administration &amp; dosage ; *Microbiota ; Female ; Clostridium Infections/therapy/microbiology ; Animals ; Vaginosis, Bacterial/therapy/microbiology ; Vagina/microbiology ; *Biological Therapy/methods ; }, abstract = {INTRODUCTION: The microbiota composition in humans varies according to the anatomical site and is crucial for maintaining homeostasis and an overall healthy state. Several gastrointestinal, vaginal, respiratory, and skin diseases are associated with dysbiosis. Alternative therapies such as microbiota transplantation can help restore microbiota normal composition and can be implemented to treat clinically relevant diseases.<br><br>AREAS COVERED: Current microbiota transplantation therapies conducted in clinical trials were included in this review (after searching on MEDLINE database from years 2017 to 2025) such as fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (rCDI) and vaginal microbiota transplantation (VMT) against bacterial vaginosis. Washed microbiota transplantation (WMT) and live biotherapeutic products (LBPs) were also reviewed.<br><br>EXPERT OPINION: In microbiota-based transplantation therapy, selecting optimal donors is a limitation. A stool or a vaginal microbiota bank should be implemented to overcome the time-consuming and expensive process of donor recruitment. Microbiota-based LBPs are also promising treatment alternatives for rCDI and other dysbiosis-associated diseases. Specific LBPs could be engineered out of donor fluids-derived strains to achieve the selection of specific beneficial microorganisms for the treatment of specific dysbiosis-associated diseases. Personalized microbiota-based treatments are promising solutions for dysbiosis-associated diseases, which remains an important necessity in clinical practice.}, }
@article {pmid40134246, year = {2025}, author = {Gao, Q and Bai, M and Qi, T and Zhai, J and Song, Y and Zhang, W and Liang, G}, title = {Changes in Vitamin D and Gut Microbiota in Pediatric Hematopoietic Stem Cell Transplantation Patients with Bloodstream Infections.}, journal = {International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition}, volume = {95}, number = {1}, pages = {26126}, doi = {10.31083/IJVNR26126}, pmid = {40134246}, issn = {0300-9831}, support = {2022QN07//Aerospace Center Hospital Youth Innovation Fund/ ; }, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; Female ; *Vitamin D/blood/analogs &amp; derivatives ; Child ; Case-Control Studies ; Prospective Studies ; Child, Preschool ; Adolescent ; Feces/microbiology ; Infant ; Bacteremia/microbiology/epidemiology/etiology ; }, abstract = {BACKGROUND: Vitamin D (VD) and gut microbiota (GM) are important variables in pediatric hematopoietic stem cell transplantation (HSCT) recipients with bloodstream infections (BSI). Both VD and GM play significant roles in immune regulation and in maintaining intestinal barrier function.<br><br>METHODS: This prospective case-control study included 48 consecutive pediatric patients who underwent HSCT, as well as 20 healthy children from the community. Plasma samples were collected pre- and post-HSCT, together with post-HSCT fecal samples. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) were measured using chemiluminescence and enzyme linked immunosorbent assay, respectively. GM was analyzed by 16S rDNA next generation sequencing.<br><br>RESULTS: The incidence of BSI in pediatric HSCT recipients was 33.3% (16/48). No significant differences in serum 25(OH)D or 1,25(OH)2D3 levels were observed between the BSI and non-BSI groups either before or after transplantation, or with the healthy control group. The &#x3b1;-diversity of GM in BSI and non-BSI patients was significantly lower than in healthy subjects. Proteobacteria were significantly more abundant in BSI patients than in non-BSI patients (p = 0.0434) or healthy controls (p = 0.0193). Pediatric HSCT patients showed significantly higher levels of Staphylococcus (p < 0.001), Pseudomonas (p < 0.001), Enterococcus (p < 0.001), Clostridium innocuum (p = 0.0175) and Enterobacter (p = 0.0394) compared to the controls, whereas the levels of Firmicutes (p = 0.009), Actinobacteria (p < 0.001), Bifidobacterium (p < 0.001) and Faecalibacterium (p < 0.001) were significantly lower. &#x3b2;-diversity analysis revealed significant population differences between the three groups.<br><br>CONCLUSIONS: These results indicate there is no practical value in monitoring VD in HSCT patients. During HSCT and BSI, the GM experiences a loss of probiotics and an increase in potential pathogens.}, }
@article {pmid40133348, year = {2025}, author = {Jing, Y and Wang, Q and Bai, F and Li, Z and Li, Y and Liu, W and Yan, Y and Zhang, S and Gao, C and Yu, Y}, title = {Age-related alterations in gut homeostasis are microbiota dependent.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {51}, pmid = {40133348}, issn = {2055-5008}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Homeostasis ; Mice ; *Aging ; *Fecal Microbiota Transplantation ; Gene Expression Profiling ; Mice, Inbred C57BL ; Transcriptome ; Colon/microbiology ; Intestinal Mucosa/microbiology/metabolism ; Male ; Computational Biology/methods ; }, abstract = {Accumulating data suggest that remodeling aged gut microbiota improves aging-related imbalance in intestinal homeostasis. However, evidence in favor of the beneficial effect of remodeling gut microbiota on intestinal stress and immune responses during aging is scarce. The current study revealed that old mice presented impaired gut barrier integrity. Transcriptome sequencing coupled with bioinformatics analysis revealed that aging altered gene expression profiles of the colon and mesenteric lymph nodes, which are involved mainly in stress and immune responses, respectively. Notably, gut microbiota was closely related to the differentially expressed genes. Microbiota depletion in old mice ameliorated gut barrier integrity and partially reversed the inflammatory factors upregulated in aging mice. Furthermore, fecal microbiota transplantation from young mice to old mice resulted in a significant improvement in intestinal barrier integrity and immune homeostasis. These findings highlight the potential of microbiota-targeted interventions on aging-related physiological processes and call for further investigation.}, }
@article {pmid40133336, year = {2025}, author = {Tillett, BJ and Dwiyanto, J and Secombe, KR and George, T and Zhang, V and Anderson, D and Duggan, E and Giri, R and Loo, D and Stoll, T and Morrison, M and Begun, J and Hill, MM and Gurzov, EN and Bell, KJ and Saad, S and Barlow, CK and Creek, DJ and Chong, CW and Mariño, E and Hamilton-Williams, EE}, title = {SCFA biotherapy delays diabetes in humanized gnotobiotic mice by remodeling mucosal homeostasis and metabolome.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2893}, pmid = {40133336}, issn = {2041-1723}, support = {2-SRA-2019-703-M-B, 201308399//Juvenile Diabetes Research Foundation Australia (JDRF Australia)/ ; 2002917, 2028813//Department of Health | National Health and Medical Research Council (NHMRC)/ ; }, mesh = {Animals ; *Fatty Acids, Volatile/metabolism ; Humans ; *Germ-Free Life ; *Diabetes Mellitus, Type 1/immunology/therapy/metabolism ; *Gastrointestinal Microbiome ; *Metabolome ; Mice ; *Homeostasis ; Intestinal Mucosa/metabolism/immunology/microbiology ; Male ; Female ; Fecal Microbiota Transplantation ; Mice, Inbred NOD ; Adult ; Biological Therapy/methods ; Immunity, Mucosal/drug effects ; }, abstract = {Type 1 diabetes (T1D) is linked to an altered gut microbiota characterized by reduced short-chain fatty acid (SCFA) production. Oral delivery of a SCFA-yielding biotherapy in adults with T1D was followed by increased SCFAs, altered gut microbiota and immunoregulation, as well as delaying diabetes in preclinical models. Here, we show that SCFA-biotherapy in humans is accompanied by remodeling of the gut proteome and mucosal immune homeostasis. Metabolomics showed arginine, glutamate, nucleotide and tryptophan metabolism were enriched following the SCFA-biotherapy, and found metabolites that correlated with glycemic control. Fecal microbiota transfer demonstrated that the microbiota of SCFA-responders delayed diabetes progression in humanized gnotobiotic mice. The protected mice increased similar metabolite pathways to the humans including producing aryl-hydrocarbon receptor ligands and reducing inflammatory mucosal immunity and increasing IgA production in the gut. These data demonstrate that a potent SCFA immunomodulator promotes multiple beneficial pathways and supports targeting the microbiota as an approach against T1D. Trial registration: Australia New Zealand Clinical Trials Registry ACTRN12618001391268.}, }
@article {pmid40131972, year = {2025}, author = {Duan, JQ and Sun, YF and Wang, X and Liu, HY and Chang, ZP and Shao, YY and Liu, JJ and Hou, RG}, title = {Shaoyao-Gancao decoction improves dyslipidemia in rats with polycystic ovary syndrome by reshaping the gut microbiota and regulating the bile acid/FXR pathway.}, journal = {Journal of Asian natural products research}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/10286020.2025.2482072}, pmid = {40131972}, issn = {1477-2213}, abstract = {This study aims to investigate the potential mechanism of Shaoyao-Gancao Decoction (SGD) in treating polycystic ovary syndrome (PCOS). Our results suggested that SGD effectively regulated estrous cycles, reduced body weight and serum lipid levels in PCOS rats. Additionally, SGD administration significantly remodeled the structure of gut microbiota, especially the BA-related bacteria. The mRNA expressions of BAs metabolism pathway-related genes were significantly changed by SGD treatment. Furthermore, transplantation of fecal microbiota from SGD rats verified these results. In conclusion, SGD could ameliorate dyslipidemia in PCOS rats by remodeling the structure of the gut microbiome and regulating the bile acid/FXR pathway.}, }
@article {pmid40131871, year = {2025}, author = {Kellingray, L and Savva, GM and Garcia-Gutierrez, E and Snell, J and Romano, S and Yara, DA and Altera, A and de Oliveira Martins, L and Hutchins, C and Baker, D and Hayhoe, A and Hacon, C and Elumogo, N and Narbad, A and Sayavedra, L}, title = {Temporal dynamics of SARS-CoV-2 shedding in feces and saliva: a longitudinal study in Norfolk, United Kingdom during the 2021-2022 COVID-19 waves.}, journal = {Microbiology spectrum}, volume = {13}, number = {5}, pages = {e0319524}, pmid = {40131871}, issn = {2165-0497}, abstract = {UNLABELLED: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originally described as a respiratory illness; however, it is now known that the infection can spread to the gastrointestinal tract, leading to shedding in feces potentially being a source of infection through wastewater. We aimed to assess the prevalence and persistence of SARS-CoV-2 in fecal and saliva samples for up to 7 weeks post-detection in a cohort of 98 participants from Norfolk, United Kingdom using RT-qPCR. Secondary goals included sequencing the viral isolates present in fecal samples and comparing the genetic sequence with isolates in the saliva of the same participant. Furthermore, we sought to identify factors associated with the presence of detectable virus in feces or saliva after a positive SARS-CoV-2 test. Saliva remained SARS-CoV-2-positive for longer periods compared to fecal samples, with all positive fecal samples occurring within 4 weeks of the initial positive test. Detectable virus in fecal samples was positively associated with the number of symptoms experienced by the individuals. Based on the genome sequencing and taxonomic classification of the virus, one donor had a distinct strain in feces compared to saliva on the same collection date, which suggests that different isolates could dominate different tissues. Our results underscore the importance of considering multiple biological samples, such as feces, in the detection and characterization of SARS-CoV-2, particularly in clinical procedures involving patient fecal material transplant. Such insights could contribute to enhancing the safety protocols surrounding the handling of patient samples and aid in devising effective strategies for mitigating the spread of coronavirus disease.<br><br>IMPORTANCE: This study provides critical insights into the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding in fecal and saliva samples, demonstrating that while viral RNA is detectable shortly after diagnosis, its prevalence declines rapidly over the course of infection. Detection was more common among individuals with more concurrent symptoms, emphasizing the potential influence of symptom burden on viral persistence. By analyzing a United Kingdom-based cohort, this study fills a significant gap in the literature, which has largely focused on Asian and North American populations, offering a geographically unique perspective on viral shedding dynamics. Our findings contribute to a globally relevant understanding of SARS-CoV-2 shedding by revealing differences in shedding durations compared to studies from other regions. These differences highlight the need for geographically diverse research to account for variations in genetic background, immune response, and healthcare practices.}, }
@article {pmid40130013, year = {2024}, author = {Wang, IC and Buffington, SA and Salas, R}, title = {Microbiota-Gut-Brain Axis in Psychiatry: Focus on Depressive Disorders.}, journal = {Current epidemiology reports}, volume = {11}, number = {4}, pages = {222-232}, pmid = {40130013}, issn = {2196-2995}, support = {I01 CX001937/CX/CSRD VA/United States ; R01 HD109095/HD/NICHD NIH HHS/United States ; R01 HD109780/HD/NICHD NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: Gut microbiota contribute to several physiological processes in the host. The composition of the gut microbiome is associated with different neurological and neurodevelopmental diseases. In psychiatric disease, stress may be a major factor leading to gut microbiota alterations. Depressive disorders are the most prevalent mental health issues worldwide and patients often report gastrointestinal symptoms. Accordingly, evidence of gut microbial alterations in depressive disorders has been growing. Here we review current literature revealing links between the gut microbiome and brain function in the context of depression.<br><br>RECENT FINDINGS: The gut-brain axis could impact the behavioral manifestation of depression and the underlying neuropathology via multiple routes: the HPA axis, immune function, the enteric nervous system, and the vagus nerve. Furthermore, we explore possible therapeutic interventions including fecal microbiota transplant or probiotic supplementation in alleviating depressive symptoms.<br><br>SUMMARY: Understanding the mechanisms by which bidirectional communication along the gut-brain axis can be dysregulated in patients with depression could lead to the development of personalized, microbiome-targeted therapies for the treatment of this disorder.}, }
@article {pmid40128912, year = {2025}, author = {Feng, Y and Chen, W and Chen, J and Sun, F and Kong, F and Li, L and Zhao, Y and Wu, S and Li, Z and Du, Y and Kong, X}, title = {Dietary emulsifier carboxymethylcellulose-induced gut dysbiosis and SCFA reduction aggravate acute pancreatitis through classical monocyte activation.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {83}, pmid = {40128912}, issn = {2049-2618}, support = {82172572//National Natural Science Foundation of China/ ; 82170659//National Natural Science Foundation of China/ ; 82072760//National Natural Science Foundation of China/ ; 2019YFC1315900//National Key R&amp;D Program of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dysbiosis/microbiology ; Mice ; *Mice, Inbred C57BL ; *Carboxymethylcellulose Sodium ; *Monocytes/metabolism ; Humans ; *Fatty Acids, Volatile/metabolism ; *Pancreatitis ; Male ; Fecal Microbiota Transplantation ; Emulsifying Agents/adverse effects ; Akkermansia ; Feces/microbiology ; Verrucomicrobia ; Disease Models, Animal ; Butyrates/metabolism ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVE: Carboxymethylcellulose (CMC), one of the most common emulsifiers used in the food industry, has been reported to promote chronic inflammatory diseases, but its impact on acute inflammatory diseases, e.g., acute pancreatitis (AP), remains unclear. This study investigates the detrimental effects of CMC on AP and the potential for mitigation through Akkermansia muciniphila or butyrate supplementation.<br><br>DESIGN: C57BL/6 mice were given pure water or CMC solution (1%) for 4 weeks and then subjected to caerulein-induced AP. The pancreas, colon, and blood were sampled for molecular and immune parameters associated with AP severity. Gut microbiota composition was assessed using 16S rRNA gene amplicon sequencing. Fecal microbiota transplantation (FMT) was used to illustrate gut microbiota's role in mediating the effects of CMC on host mice. Additional investigations included single-cell RNA sequencing, monocytes-specific C/EBP&#x3b4; knockdown, LPS blocking, fecal short-chain fatty acids (SCFAs) quantification, and Akkermansia muciniphila or butyrate supplementation. Finally, the gut microbiota of AP patients with different severity was analyzed.<br><br>RESULTS: CMC exacerbated AP with gut dysbiosis. FMT from CMC-fed mice transferred such adverse effects to recipient mice, while single-cell analysis showed an increase in classical monocytes in blood. LPS-stimulated C/EBP&#x3b4;, caused by an impaired gut barrier, drives monocytes towards classical phenotype. LPS antagonist (eritoran), Akkermansia muciniphila or butyrate supplementation ameliorates CMC-induced AP exacerbation. Fecal Akkermansia muciniphila abundance was negatively correlated with AP severity in patients.<br><br>CONCLUSIONS: This study reveals the detrimental impact of CMC on AP due to gut dysbiosis, with Akkermansia muciniphila or butyrate offering potential therapeutic avenues for counteracting CMC-induced AP exacerbation. Video Abstract.}, }
@article {pmid40127764, year = {2025}, author = {Verbiest, A and Andersen, JHM and Hvistendahl, MK and Tóth, J and Vandermeulen, G and De Meyere, L and Joly, F and Verbeke, K and Jeppesen, PB and Vanuytsel, T}, title = {Transferability of metabolic balance studies in short bowel syndrome.}, journal = {Clinical nutrition ESPEN}, volume = {67}, number = {}, pages = {377-386}, doi = {10.1016/j.clnesp.2025.03.029}, pmid = {40127764}, issn = {2405-4577}, abstract = {BACKGROUND: Metabolic balance studies (MBS) are the gold standard method to assess the intestinal absorptive function in patients with short bowel syndrome (SBS). During a full MBS, patients are admitted to the hospital to collect duplicates of all ingested foods and drinks, as well as their fecal and urinary output, typically over a 72-h period. These collections are further processed to assess absorption of energy, macronutrients (nitrogen, fat and carbohydrate) and electrolytes (sodium, potassium, calcium and magnesium). Full MBS require dedicated laboratory personnel, equipment, knowledge and experience, which explains why they are currently only performed in one center.<br><br>AIM: We aimed to explore the transferability of full MBS in patients with SBS from the reference center to a clinical center that was new to and unexperienced in MBS.<br><br>METHODS: A collaboration between the centers was initiated to transfer knowledge on how to perform MBS collections, how to process and how to analyze energy, macronutrient and electrolyte content in the collected samples. At practical level, transferability included successful MBS collecting and processing. At analytical level, transferability included the lyophilization of homogenized samples at both centers. The powder that was created at the reference center was measured at both centers to assess the transferability of the analytical methods; while the site-specific powder was measured at the corresponding center to determine full process transferability. The intraclass correlation coefficient (ICC) was calculated to define the absolute agreement between both centers.<br><br>RESULTS: A total of 21 MBS were performed in 7 patients with SBS at the new center. A total of 189 samples were collected, equally distributed among combined meals and drinks (n&#xa0;=&#xa0;63), fecal output (n&#xa0;=&#xa0;63) and urinary output (n&#xa0;=&#xa0;63). Meals and drinks samples and fecal output samples were processed in the new center and lyophilized at both centers, with a perfect reliability for dry matter between the centers (ICC&#xa0;=&#xa0;1). At the level of method transferability, there was an excellent absolute agreement between centers for energy and nitrogen analyses (ICC>0.9). For fat, the mean coefficients of variation (cv) between centers for fecal output (6.3&#xa0;%) and meals and drinks (12.0&#xa0;%) were higher, but ICC showed excellent (0.957) to good (0.787) agreement, respectively. Carbohydrate results differed more between the centers (mean cv of 17.5&#xa0;% for fecal output and 16.4&#xa0;% for meals and drinks), translating into a moderate (meals and drinks, ICC&#xa0;=&#xa0;0.654) to good (fecal output, ICC&#xa0;=&#xa0;0.812) reliability. Similar results and degrees of agreement as obtained for the method transferability were observed with the site-specific powder.<br><br>CONCLUSION: Our study showed the feasibility of a full MBS transferability to a new unexperienced center with promising agreement of the results obtained between both centers. Our findings aim to inspire other specialized intestinal failure centers to adopt the full MBS methodology for both clinical practice and research purposes.}, }
@article {pmid40123400, year = {2025}, author = {Tian, HL and Wang, L and Ma, CL and Yang, B and Li, L and Ye, C and Zhao, D and Lin, ZL and Cui, JQ and Liu, YK and Zhu, WY and Zhou, SL and Li, N and Chen, QY}, title = {[Fecal microbiota transplantation for the treatment of intestinal disorders: An analysis of treatment of 15 000 patients].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {296-303}, doi = {10.3760/cma.j.cn441530-20250114-00025}, pmid = {40123400}, issn = {1671-0274}, support = {82100698//National Natural Science Foundation of China/ ; 2021SYPDRC045//the Climb Plan of Tenth People's Hospital of Tongji University/ ; 202240177//Shanghai Health Commission's Surface Project/ ; }, mesh = {Humans ; Female ; Male ; Middle Aged ; *Fecal Microbiota Transplantation/methods ; Retrospective Studies ; Adult ; *Constipation/therapy ; Treatment Outcome ; Irritable Bowel Syndrome/therapy ; Diarrhea/therapy ; Intestinal Diseases/therapy/microbiology ; Inflammatory Bowel Diseases/therapy ; Clostridium Infections/therapy ; Dysbiosis/therapy ; Autistic Disorder/therapy ; }, abstract = {Objective: To examine the long-term efficacy and complications of fecal microbiota transplantation (FMT) for the treatment of diseases related to intestinal dysbiosis. Methods: This was a retrospective descriptive study. Relevant data were collected from the records of 15 000 patients who had undergone FMT and been followed up for more than 3 months during the period from May 2017 to September 2024. The patient cohort comprised 3746 male and 11 254 female patients aged (45.3±12.2) years. The inclusion criterion was meeting the indications for FMT. Application of this criterion yielded 8258 patients with constipation, 684 with Clostridium difficile infection, 1730 with chronic diarrhea, 510 with inflammatory bowel disease, 432 with radiation enteritis, 1940 with irritable bowel syndrome, 365 with autism, 870 with postoperative gastrointestinal dysfunction, and 211 with neurodegenerative diseases. The three routes of delivering FMT comprised infusion of an enterobacterial solution through a nasoenteric tube into the jejunum for 6 consecutive days (upper gastrointestinal FMT group, 11 125 patients), oral intake of enterobacterial capsules for 6 consecutive days (oral capsule FMT, 3597 patients), and a single injection of a bacterial solution into the colon via colonoscopy (lower gastrointestinal FMT group, 278 patients). Other treatments were discontinued during the treatment and follow-up period and administration of other medications was not recommended unless absolutely necessary. The primary outcomes were the efficacy of FMT after 3, 12 and 36 months of treatment, and improvement in chronic constipation, C. difficile infection, chronic diarrhea, inflammatory bowel disease, radiation enteritis, irritable bowel syndrome, post-surgery gastrointestinal dysfunction, and autism. Other outcomes included the occurrence of short-term (within 2 weeks after treatment) and long-term (within 36 months after treatment) adverse reactions. Results: At 3, 12 and 36 months after treatment, the overall rates of effectiveness of treatment were 71.8% (10 763/15 000), 64.4% (7600/11 808) and 58.8% (3659/6218), respectively. Specifically, the rates of clinical improvement were 70.3% (5805/8258), 62.6% (3970/6345), and 56.5% (1894/3352), respectively, for constipation; 85.8% (587/684), 72.3% (408/564), and 67.3% (218/324), respectively, for C.difficile infection; 81.0% (1401/1730), 78.1% (1198/1534), and 72.3% (633/876), respectively, for chronic diarrhea; 64.3% (328/510), 52.3% (249/476), and 46.6 % (97/208), respectively, for inflammatory bowel disease; 77.3% (334/432), 65.4% (212/324), and 53.6% (82/153), respectively, for radiculitis; 70.6% (1370/1940), 64.5% (939/1456), and 60.4% (475/786), respectively, for irritable bowel syndrome; 75.3% (275/365), 70.0% (201/287), and 63.6% (112/176), respectively, for autism; 65.3% (568/870), 54.3% (355/654), and 46.5% (114/245), respectively, for post-surgical gastrointestinal dysfunction; and 45.0% (95/211), 40.5% (68/168), and 34.7% (34/98), respectively, for neurodegenerative diseases. At 3, 12, and 36 months post-treatment, clinical improvement rates were 77.1% (8580/11 125), 67.1% (6437/9595), and 62.1% (3196/5145), respectively, in the upper gastrointestinal route group; and 57.3% (2062/3597), 53.6% (1115/2081), and 45.0% (453/1006), respectively, in the oral capsule group; and 43.5% (121/278) , 36.4% (48/132) and 14.9% (10/67), respectively, in the lower gastrointestinal route group. No serious adverse reactions occurred during treatment or follow-up. The most common adverse reactions in the upper gastrointestinal route group, oral capsule group, and lower gastrointestinal route group were respiratory discomfort (20.4%, 2269/11 125), nausea and vomiting on swallowing the capsule (7.6%, 273/3597), and diarrhea (47.5%, 132/278), respectively; these symptoms resolved at the end of treatment. At 36 months of follow-up, 19 patients reported exacerbation of symptoms of pre-existing diseases and there had been 16 deaths that were not directly related to FMT. Additionally, no systemic diseases had developed after FMT. Conclusion: FMT for the treatment of intestinal dysfunction associated with disorders of the intestinal flora and related extraintestinal diseases is effective and not associated with serious adverse events.}, }
@article {pmid40123399, year = {2025}, author = {Li, L and Wang, L and Guo, GG and Fan, YH and Shi, JG and Yuan, XG and Dong, XS and Liu, L and Li, N and Chen, QY}, title = {[Evaluation of the efficacy and safety of multi-center fecal microbiota transplantation for treatment of functional constipation: A retrospective real-world study].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {288-295}, doi = {10.3760/cma.j.cn441530-20250102-00001}, pmid = {40123399}, issn = {1671-0274}, support = {82470701//National Natural Science Foundation of China/ ; YJXYS-C-003//Research Physician Training Program of Shanghai 10th People's Hospital/ ; 20234Y0079//Scientific Research Project of Shanghai Municipal Health Commission/ ; }, mesh = {Humans ; *Constipation/therapy ; Male ; Female ; Retrospective Studies ; Middle Aged ; *Fecal Microbiota Transplantation/methods ; Adult ; Treatment Outcome ; Aged ; Quality of Life ; }, abstract = {Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for treating functional constipation, analyze the incidence of, and factors that influence, adverse events, and provide scientific evidence for optimizing FMT treatment. Methods: This retrospective, multicenter, single-arm, pre-post real-world study included 1529 patients with functional constipation from four clinical centers. Eligibility criteria comprised meeting the diagnostic criteria for functional constipation, having undergone at least one FMT treatment, complete pre- and post-treatment data available, and age ≥18 years. Patients who had received other interventions affecting gut function within 1 month before treatment and those with severe organic diseases or immune deficiencies were excluded. Applying the above criteria yielded 1529 eligible patients with functional constipation from four medical centers (1405 from the Shanghai Tenth People's Hospital Affiliated to Tongji University, 20 from the Central Hospital of Wuhan, 67 from the Shanxi Bethune Hospital and 37 from the Longgang District People's Hospital of Shenzhen). The study cohort comprised 746 male (48.8%) and 783 female patients (51.2%) of mean age (51.4 ± 17.4) years, mean body mass index (26.4 ± 4.9) kg/m[2], and mean duration of disease (15.0 ± 8.3) years. The primary outcomes were the incidence, types, and severity of adverse reactions during treatment, and their impact on patients' quality of life. Secondary outcomes included: (1) the efficacy of FMT in treating constipation. This was assessed based on changes in Patient Assessment of Constipation Symptoms (PAC-SYM) scores, where higher score indicates worse symptom. (2) Subjective satisfaction, evaluated through questionnaires or rating scales, reflecting patients' acceptance of and satisfaction with the treatment, with scores ranging from 1 to 5, where higher scores indicated greater satisfaction. Paired t-tests and Wilcoxon signed-rank tests were used to evaluate changes in symptom scores and biochemical indicators before and after treatment. Logistic regression was performed to analyze factors influencing adverse events, and subgroup analyses to explored differences in efficacy between patient groups. Results: In this cohort of 1529 patients with functional constipation, adverse reactions were primarily mild to moderate (1048/1529,68.5%). They comprised fever in 54 patients (3.5%), dizziness or fatigue in 218 (14.3%), throat discomfort in 806 (52.7%), nausea and vomiting in 166 (10.9%), and abdominal distension or pain in 415 (27.1%). According to multivariate logistic regression analysis, PAC-SYM scores were associated with the rate of adverse reactions, higher scores indicating a lower risk (OR = 0.958, 95% CI: 0.923-0.993, P=0.021). Among the 1529 patients, 274 (17.9%) underwent two or more treatment courses. After one treatment course, the patients' PAC-SYM scores decreased from (37.7 ± 3.2) pre-treatment to (23.7 ± 8.6) (mean difference 14.0 ± 9.1). PAC-SYM scores decreased by (20.7 ± 7.7) after two courses of FMT, and by (19.4 ± 6.3) after three courses. After treatment, 50.7%(775/1529) of patients reported satisfaction scores of ≥4. Adverse reactions impacted satisfaction; specifically, dizziness/fatigue, throat discomfort, and abdominal distension/pain were significantly associated with satisfaction (all P < 0.05). Conclusions: FMT achieved good relief of symptoms of functional constipation and multiple treatment courses have a cumulative effect. Adverse reactions, mainly dizziness/fatigue, throat discomfort, and abdominal distension/pain, had significant negative impacts on patient satisfaction.}, }
@article {pmid40123398, year = {2025}, author = {Xu, Y and Ye, C and Li, N and Chen, QY}, title = {[Challenges and progress in in the clinical application of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {266-273}, doi = {10.3760/cma.j.cn441530-20241224-00420}, pmid = {40123398}, issn = {1671-0274}, support = {82470701, 82401727//National Natural Science Foundation of China/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; Feces/microbiology ; Clostridium Infections/therapy ; Inflammatory Bowel Diseases/therapy/microbiology ; Irritable Bowel Syndrome/therapy/microbiology ; Gastrointestinal Diseases/therapy/microbiology ; Diarrhea/therapy/microbiology ; Clostridioides difficile ; }, abstract = {With the deepening understanding of the role of gut microbiota in human health and disease, fecal microbiota transplantation has gained widespread attention as an emerging therapeutic approach in recent years. This technique involves the transplantation of microbial communities from the feces of healthy donors into patients to reconstruct or improve the gut microbiota structure, thereby achieving therapeutic goals. Fecal microbiota transplantation has become an effective method for treating recurrent or refractory Clostridium difficile infections and has shown good therapeutic effects and safety in clinical trials for various gastrointestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, slow transit constipation, and chronic diarrhea. Moreover, its application has been extended to research in metabolic diseases and neurological disorders, which are not directly related to the gut. However, the clinical efficacy of fecal microbiota transplantation still needs improvement, and there are many challenges regarding specific application strategies that remain to be addressed. This article discusses the current progress and challenges of fecal microbiota transplantation strategies and reviews cutting-edge interventional methods such as small intestine microbiota intervention and bacteriophage therapy, aiming to provide reference for further research in fecal microbiota transplantation.}, }
@article {pmid40123397, year = {2025}, author = {Jin, YF and Wen, WJ and Zuo, T}, title = {[Phages in human health and gut microbiota transplantation therapy].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {261-265}, doi = {10.3760/cma.j.cn441530-20241130-00387}, pmid = {40123397}, issn = {1671-0274}, support = {82172323, 32100134//National Natural Science Foundation of China/ ; 2024A1515010533//Guangdong Provincial Natural Science Foundation/ ; 202206010014//Guangzhou Key R&amp;D program/ ; 2022JBGS03//Seed Fund from the Sixth Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Bacteriophages/physiology ; Phage Therapy/methods ; Bacteria ; }, abstract = {Phages, prokaryotic viruses widely present in the human, are a crucial component of the gut microbiome. They play a significant role in human health and the development of diseases. Emerging evidence indicates that phages can interact with bacteria to affect their abundance, metabolism, and antibiotic resistance, thereby influencing the balance of the gut microbiota. In addition, phages also contribute to the gut immune response, and can become dysregulated in a range of immune-related diseases. Gut phages also carry important roles in fecal microbiota transplantation (FMT) for disease treatment. Phages can target specific bacterial members and communities, thereby reduce the risk of bacterial infections or the presence of bacteria, and maintain the stability of the gut microbiome. However, gut phageome research is still in its infancy and additional basic and clinical researches are required to evaluate its species composition, mechanisms of pathogenicity or protection, as well as its efficacy and safety.}, }
@article {pmid40123396, year = {2025}, author = {Wang, XJ and Zhao, D and Qin, YH and Yu, LT and Cao, Z and Liu, WH and Yang, B and Li, N and Chen, QY and Qin, HL}, title = {[How close is fecal microbiota transplantation to moving to precision medicine?].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {254-260}, doi = {10.3760/cma.j.cn441530-20241220-00415}, pmid = {40123396}, issn = {1671-0274}, support = {82300753, 82330093, 82470701//National Natural Science Foundation of China/ ; 2024YFA1307101//National Key R&amp;D Program/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Precision Medicine/methods ; Gastrointestinal Microbiome ; Feces/microbiology ; China ; }, abstract = {Fecal microbiota transplantation (FMT) has the potential to rebuild the intestinal microbiome of patients, which can influence the disease course, alleviate symptoms, or even cure the disease. It is seen as a promising breakthrough for treating major chronic diseases that are difficult to manage. Currently, FMT therapy has been clinically studied for over 80 diseases and has led to significant breakthroughs. However, there are still four main challenges: (1) identifying the effective characteristics of donor microbiota and ensuring precise matching between donors and recipients; (2) understanding the pathways and molecular mechanisms by which key FMT bacteria and metabolites improve disease outcomes; (3) studying strain interactions and colonization mechanisms to restore intestinal microbiota balance; and (4) refining the precision of microbiome and functional microbiota transplantation. To address these clinical challenges, this article reviews the latest research both domestically and internationally, outlines the response patterns of FMT therapy, examines the reasons behind FMT failure, and explores future directions for the development of FMT. The aim is to accelerate the scientific and precise advancement of FMT technology in China.}, }
@article {pmid40123393, year = {2025}, author = {,  and ,  and , }, title = {[Consensus of Chinese experts on gut microbiota and fecal microbiota transplantation in inflammatory bowel disease (2025 edition)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {225-235}, doi = {10.3760/cma.j.cn441530-20241224-00422}, pmid = {40123393}, issn = {1671-0274}, support = {2022YFC2010101//Ministry of Science and Technology Major Research and Development Program/ ; 2022YFA1304100//Ministry of Science and Technology Major Research and Development Program Subproject/ ; 82470701, 81700480, 82300753//National Natural Science Foundation of China/ ; 076478684Q/2023-00154//Shanghai Municipal Health Commission Key Project/ ; ZJ2022-ZD-005//Shanghai Zhangjiang National Independent Innovation Demonstration Zone Special Development Fund Major Project/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Gastrointestinal Microbiome ; China ; *Consensus ; Feces/microbiology ; Donor Selection ; }, abstract = {In recent years, significant progress has been made in the clinical and basic research on fecal microbiota transplantation (FMT) for the treatment of inflammatory bowel disease (IBD). With the continuous application of new microbiota-based diagnostic and therapeutic concepts in clinical practice, it is imperative to standardize the diagnostic and therapeutic processes of FMT for IBD and provide consensus recommendations based on the latest evidence from evidence-based medicine for clinical practitioners. Organized by the Chinese Society for Parenteral and Enteral Nutrition of the Chinese Medical Association, the Gut Microbiota and FMT Committee of the Chinese Society for Human Health Sciences, and the Gut Microbiota Committee of the Shanghai Preventive Medicine Association, and with reference to the latest international consensus and relevant research advancements, this consensus integrates the clinical practice experience of domestic experts to establish the "Consensus of Chinese experts on gut microbiota and fecal microbiota transplantation in inflammatory bowel disease (2025 edition)". This consensus provides 29 recommendations focusing on the selection of FMT indications, gut microbiota analysis, donor selection and quality control for IBD transplantation, considerations during the transplantation period, selection of transplantation routes and dosages, management of FMT-related complications, and future research directions, aiming to offer standardized guidance for the clinical application of FMT in the treatment of IBD.}, }
@article {pmid40122676, year = {2025}, author = {González-Correa, C and Moleón, J and Miñano, S and Robles-Vera, I and de la Visitación, N and Guerra-Hernández, E and Toral, M and Jiménez, R and Duarte, J and Romero, M}, title = {Protective Effect of Dietary Fiber on Blood Pressure and Vascular Dysfunction Through Regulation of Sympathetic Tone and Immune Response in Genetic Hypertension.}, journal = {Phytotherapy research : PTR}, volume = {39}, number = {4}, pages = {1858-1875}, doi = {10.1002/ptr.8484}, pmid = {40122676}, issn = {1099-1573}, support = {B-CTS-046-UGR18//Junta de Andaluc&#xed;a and European Regional Development Fund (ERDF)/ ; CTS 164//Junta de Andaluc&#xed;a and European Regional Development Fund (ERDF)/ ; P20_00193//Junta de Andaluc&#xed;a and European Regional Development Fund (ERDF)/ ; MCIN/AEI/10.13039/501100011033//Ministry of Science and Innovation- State Research Agency of Spain (MSI-SRA)/ ; PID2020-116347RB-I00//Ministry of Science and Innovation- State Research Agency of Spain (MSI-SRA)/ ; FJC2021-048099-I//Ministerio de Economia y Competitividad (MINECO)/ ; FPU18/02561//Ministerio de Economia y Competitividad (MINECO)/ ; FPU22/00397//Ministerio de Economia y Competitividad (MINECO)/ ; }, mesh = {Animals ; Rats, Inbred SHR ; *Hypertension/immunology/genetics/prevention &amp; control ; Male ; Rats, Inbred WKY ; *Dietary Fiber/pharmacology ; *Blood Pressure/drug effects ; Gastrointestinal Microbiome/drug effects ; Rats ; Oxidative Stress/drug effects ; Fecal Microbiota Transplantation ; *Sympathetic Nervous System/drug effects ; Fatty Acids, Volatile/metabolism ; T-Lymphocytes, Regulatory ; }, abstract = {The mechanisms underlying the antihypertensive effect of dietary fibers remain poorly understood. This study investigates whether dietary fiber supplementation can prevent cardiovascular damage and high blood pressure in a genetic model of neurogenic hypertension. Six-week-old male spontaneously hypertensive rats (SHR) and their respective normotensive control, Wistar Kyoto rats (WKY), were divided into four groups: Untreated WKY, untreated SHR, SHR treated with resistant starch (SHR + RS), and SHR treated with inulin-type fructans (SHR + ITF) for 12 weeks. Additionally, a faecal microbiota transplantation (FMT) experiment was conducted, transferring faecal content from treated SHR donors to recipient SHRs. A diet rich in RS fiber reduced vascular oxidative stress, inflammation, and high blood pressure. These protective effects were associated with a reshaped gut microbiota, leading to increased short-chain fatty acid production, reduced endotoxemia, decreased sympathetic activity, and a restored balance between Th17 and Treg lymphocytes in mesenteric lymph nodes and aorta. Elevated plasma levels of acetate and butyrate in the SHR + RS group correlated with increased expression of aortic GPR41, GRP43 and PPARδ. Conversely, ITF treatment failed to prevent hypertension or endothelial dysfunction in SHR. FMT from the SHR + RS group to recipient SHR partially replicated these beneficial effects. This study highlights the antihypertensive benefits of dietary insoluble RS fiber, which are attributed to enhanced short-chain fatty acids production in the gut. This leads to improved gut permeability, reduced sympathetic tone, and diminished vascular T-cell accumulation. Therefore, dietary interventions with RS fiber may offer promising therapeutic strategies for preventing hypertension.}, }
@article {pmid40122597, year = {2025}, author = {Su, R and Wen, W and Jin, Y and Cao, Z and Feng, Z and Chen, J and Lu, Y and Zhou, G and Dong, C and Gao, S and Li, X and Zhang, H and Chao, K and Lan, P and Wu, X and Philips, A and Li, K and Gao, X and Zhang, F and Zuo, T}, title = {Dietary whey protein protects against Crohn's disease by orchestrating cross-kingdom interaction between the gut phageome and bacteriome.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-334516}, pmid = {40122597}, issn = {1468-3288}, abstract = {BACKGROUND: The gut microbiome and diet are important factors in the pathogenesis and management of Crohn's disease (CD). However, the role of the gut phageome under dietary influences is unknown.<br><br>OBJECTIVE: We aim to explore the effect of diet on the gut phageome-bacteriome interaction linking to CD protection.<br><br>DESIGN: We recruited CD patients and healthy subjects (n=140) and conducted a multiomics investigation, including paired ileal mucosa phageome and bacteriome profiling, dietary survey and phenome interrogation. We screened for the effect of diet on the gut phageome and bacteriome, as well as its epidemiological association with CD risks. The underlying mechanisms were explored in target phage-bacteria monocultures and cocultures in vitro and in two mouse models in vivo.<br><br>RESULTS: On dietary screening in humans, whey protein (WP) consumption was found to profoundly impact the gut phageome and bacteriome (more pronounced on the phageome) and was associated with a lower CD risk. Indeed, the WP reshaped gut phageome can causally attenuate intestinal inflammation, as shown by faecal phageome versus bacteriome transplantation from WP-consuming versus WP-non-consuming mice to recipient mice. Mechanistically, WP induced phage (a newly isolated phage AkkZT003P herein) lysis of the mucin-foraging bacterium Akkermansia muciniphila, which unleashed the symbiotic bacterium Streptococcus thermophilus to counteract intestinal inflammation.<br><br>CONCLUSION: Our study charted the importance of cross-kingdom interaction between gut phage and bacteria in mediating the dietary effect on CD protection. Importantly, we uncovered a beneficial dietary WP, a keystone phage AkkZT003P, and a probiotic S. thermophilus that can be used in CD management in the future.}, }
@article {pmid40120791, year = {2025}, author = {Xu, DQ and Geng, JX and Gao, ZK and Fan, CY and Zhang, BW and Han, X and He, LQ and Dai, L and Gao, S and Yang, Z and Zhang, Y and Arshad, M and Fu, Y and Mu, XQ}, title = {To explore the potential combined treatment strategy for colorectal cancer: Inhibition of cancer stem cells and enhancement of intestinal immune microenvironment.}, journal = {European journal of pharmacology}, volume = {998}, number = {}, pages = {177533}, doi = {10.1016/j.ejphar.2025.177533}, pmid = {40120791}, issn = {1879-0712}, abstract = {BACKGROUND: The antibiotic salinomycin, a well-known cancer stem cell inhibitor, may impact the diversity of the intestinal microbiota in colorectal cancer (CRC) mice, which plays a pivotal role in shaping the immune system. This study explores the anti-cancer effects and mechanisms of combining salinomycin and fecal microbiota transplantation (FMT) in treating CRC.<br><br>METHODS: FMT was given via enema, while salinomycin was injected intraperitoneally into the CRC mouse model induced by azoxymethane/dextran sodium sulfate.<br><br>RESULTS: In CRC mice, a large number of LGR5-labeled cancer stem cells and severe disturbances in the intestinal microbiota were observed. Interestingly, salinomycin inhibited the proliferation of cancer stem cells without exacerbating the microbial disorder as expected. In comparison to salinomycin treatment, the combination of salinomycin and FMT significantly improved pathological damage and restored intestinal microbial diversity, which is responsible for shaping the anti-cancer immune microenvironment. The supplementation of FMT significantly increased the levels of propionic acid and butyric acid while also promoting the infiltration of CD8[+] T cells and Ly6G[+] neutrophils, as well as reducing F4/80[+] macrophage recruitment. Notably, cytokines that were not impacted by salinomycin exhibited robust reactions to alterations in the gut microbiota. These included pro-inflammatory factors (IL6, IL12b, IL17, and IL22), chemokine-like protein OPN, and immunosuppressive factor PD-L1.<br><br>CONCLUSIONS: Salinomycin plays the role of "eliminating pathogenic qi," targeting cancer stem cells; FMT plays the role of "strengthening vital qi," reversing the intestinal microbiota disorder and enhancing anti-cancer immunity. They have a synergistic effect on the development of CRC.}, }
@article {pmid40120542, year = {2025}, author = {Luo, F and Yang, J and Song, Z and Zhao, Y and Wang, P and Liu, K and Mou, X and Liu, W and Li, W}, title = {Renshen Zhuye decoction ameliorates high-fat diet-induced obesity and insulin resistance by modulating gut microbiota and metabolic homeostasis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {141}, number = {}, pages = {156655}, doi = {10.1016/j.phymed.2025.156655}, pmid = {40120542}, issn = {1618-095X}, mesh = {Animals ; *Insulin Resistance ; *Gastrointestinal Microbiome/drug effects ; Diet, High-Fat/adverse effects ; *Drugs, Chinese Herbal/pharmacology ; *Obesity/drug therapy/metabolism ; Male ; Homeostasis/drug effects ; Mice ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Lipid Metabolism/drug effects ; Energy Metabolism/drug effects ; }, abstract = {BACKGROUND: Obesity, characterized by excessive adipose tissue accumulation, has become a global health challenge with rapidly increasing prevalence. It contributes significantly to metabolic disorders including insulin resistance (IR). Renshen-zhuye decoction (RZD), a traditional Chinese medicine formula historically used for diabetes, shows potential for improving metabolic parameters, but its effects and mechanisms in obesity and insulin resistance remain unclear.<br><br>PURPOSE: This study aimed to evaluate the therapeutic benefits of RZD on obesity and insulin resistance, and to elucidate the underlying mechanisms through which it improves glucose and lipid metabolism.<br><br>METHODS: The role of RZD was evaluated in a high-fat diet (HFD) mouse model. The formula was characterized using UPLC-MS. Comprehensive analyses including histopathological staining, immunofluorescence, biochemical assays, 16S rRNA gene sequencing of gut microbiota, and non-targeted metabolomic analysis were performed. To validate the role of gut microbiota, we employed antibiotic treatment (ABX) to deplete intestinal flora and conducted fecal microbiota transplantation (FMT) experiments.<br><br>RESULTS: RZD treatment dose-dependently alleviated HFD-induced dyslipidemia and insulin resistance, improving glucose tolerance, insulin sensitivity, and energy expenditure. Gut microbiota analysis revealed that RZD significantly modulated the composition of intestinal flora and their metabolic profiles. Additionally, RZD reduced intestinal and systemic inflammation by enhancing intestinal barrier integrity, particularly through increased expression of tight junction proteins such as Occludin. Importantly, the beneficial effects of RZD on weight management and glucose homeostasis were antagonized by antibiotic intervention, while FMT experiments confirmed that these improvements were mediated through gut microbiota modulation.<br><br>CONCLUSION: This study provides new insights into RZD's modulatory effects on gut microbiota and subsequent improvements in obesity-related metabolic parameters. RZD alleviates HFD-induced obesity and insulin resistance in mice by modulating gut microbiota composition and function, which subsequently improves intestinal barrier integrity, reduces inflammation, and enhances metabolic homeostasis.}, }
@article {pmid40120240, year = {2025}, author = {Gao, C and Chen, Y and Zhang, Z and Xu, D and Liu, X and Wang, D and Shi, L and Wang, X and Chen, H and Hao, E}, title = {LAYING RATE WAS CORRELATED WITH MICROBIAL Fecal microbiota transplantation improves the laying performance by changing the gut microbiota composition in late laying period.}, journal = {Poultry science}, volume = {104}, number = {5}, pages = {105064}, pmid = {40120240}, issn = {1525-3171}, abstract = {This research investigated the differences and succession patterns of microbes in different ages, the performance of laying hens, and the effect of Fecal Microbiota Transplantation (FMT) on aged laying hens. First, based on the different laying rates and age, we divided the laying hens into four groups: 75-week-old high-yield (OH, laying rate (LR) > 90%), 75-week-old low-yield (OL, LR < 60%), 75-week-old non-laying hens (OZ, LR = 0%) and 35-week-old high-yield (YH, LR > 90%) with 5 replicates in each group and 6 chickens in each replicate. The microbial metabolic patterns between different ages and laying rates were determined using 16S rDNA technology. Then, to verify the results of microbiome research, we utilized FMT technology to transplant the gut microbiota from OH to OZ (OZFMT-OH), thereby revealing the connection between gut microbes and production performance. The results showed that high-yielding hens (YH and OH groups) had higher levels of Superoxide dismutase (SOD) and Immunoglobulin A (IgA) compared to OL and OZ groups. The Villus height to Crypt depth ratio(V/C) was significantly higher in the YH group than in 75-week-old hens (P < 0.05). Alpha diversity indicated higher microbial diversity in the YH group compared to older hens (P < 0.05), with YH hens harboring more Megamonas, OH hens more Bacteroides, and OL and OZ groups showing higher levels of harmful bacteria. The villus height, V/C, mucosal layer thickness, cup cell number acetic acid level, and LR in the OZFMT-OH group were significantly higher than those in the OZ group (P < 0.05), while the IL-2 level, crypt depth and cecal intestinal wall thickness were significantly lower than those in OZ group (P < 0.05). FMT also changed the morphological structure of grade follicles and small yellow follicles, improved the microbe composition of cecum and increased Bacteroides abundance. In the late laying period, if the intestinal flora cannot maintain the dynamic balance and carry out timely replacement, the production performance may be decreased, and the increase of Bacteroides abundance in the intestinal tract can improve the intestinal health and production performance of laying hens in the late laying period.}, }
@article {pmid40118401, year = {2025}, author = {Zhang, J and Zhou, J and He, Z and Xia, Z and Liu, H and Wu, Y and Chen, S and Wu, B and Li, H}, title = {Salidroside attenuates NASH through regulating bile acid-FXR/TGR5 signaling pathway via targeting gut microbiota.}, journal = {International journal of biological macromolecules}, volume = {307}, number = {Pt 4}, pages = {142276}, doi = {10.1016/j.ijbiomac.2025.142276}, pmid = {40118401}, issn = {1879-0003}, mesh = {Animals ; *Glucosides/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Phenols/pharmacology ; *Bile Acids and Salts/metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism/drug therapy/microbiology/pathology ; *Signal Transduction/drug effects ; Mice ; *Receptors, G-Protein-Coupled/metabolism ; Male ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {Nonalcoholic steatohepatitis (NASH) is a significant threat to human health. Our previous study revealed that salidroside attenuated NASH and regulated the gut microbiota. However, whether the therapeutic effect of salidroside depends on gut microbiota remains to be determined. Therefore, we conducted further experiments to elucidate the essential functions of gut microbiota-associated metabolic pathways in the anti-NASH effects of salidroside. Our results showed that salidroside effectively alleviated lipid accumulation and inflammatory injury in NASH mice. 16S rRNA sequencing revealed that salidroside increased the abundance of Bacteroides. Mice receiving fecal microbiota transplantation (FMT) from salidroside-treated also presented less hepatic steatosis and higher abundance of Bacteroides. Antibiotics eliminated the effects of salidroside on hepatic steatosis and the gut microbiota. Mechanistically, salidroside and FMT from salidroside-treated altered the bile acid (BA) profile by decreasing the levels of conjugated BAs and tauro-α/β-muricholic acid and activated downstream farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Furthermore, we found that inhibitors of bile salt hydrolase (BSH) and FXR/TGR5 abolished the effects of salidroside and reduced downstream carnitine palmitoyltransferase 1α and lipoprotein lipase expression. These data demonstrate that salidroside attenuated NASH via gut microbiota-BA-FXR/TGR5 signaling pathway and reveal the underlying mechanism of salidroside on NASH.}, }
@article {pmid40118127, year = {2025}, author = {Wu, S and Qiao, L and Liu, H and Li, YL and Wang, R and Yin, Y and Li, E and Wang, L and Guan, X and Yin, L and Liu, Q and Peng, X and Zhang, Y and Yang, Z and Zuo, L and Zhang, C}, title = {Age related gut microbiota regulates energy-related metabolism to influence natural aging phenotypes in the heart.}, journal = {Experimental gerontology}, volume = {203}, number = {}, pages = {112734}, doi = {10.1016/j.exger.2025.112734}, pmid = {40118127}, issn = {1873-6815}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Aging/metabolism/physiology ; Male ; Fecal Microbiota Transplantation ; *Energy Metabolism/physiology ; Rats ; *Myocardium/metabolism ; Positron Emission Tomography Computed Tomography ; *Heart/physiology ; Oxidative Stress ; Phenotype ; Autophagy ; Rats, Sprague-Dawley ; RNA, Ribosomal, 16S ; }, abstract = {As the population ages, problems pertaining to health and life expectancy due to the aging heart have become increasingly prominent. The gut microbiota has become a potential therapeutic target in several diseases, including cardiovascular diseases. Current studies on the roles of the gut microbiota in the cardiovascular system have focused mainly on cardiovascular diseases; therefore, the effects of the gut microbiota on the natural aging of myocardial tissue remain unclear. The present study aimed to explore the roles and mechanisms of the gut microbiota and related metabolites in the natural aging of the heart. Animal models of fecal microbiota transplantation (FMT) were established in elderly and young rats. 16S rRNA sequencing revealed that the gut microbiota of the recipients shifted toward the profile of the donors, with concomitant cardiac structure and diastolic function changes detected via ultrasound and positron emission tomography-computed tomography (PET-CT). A group of significantly enriched myocardial metabolites detected by LC/MS were involved in the fatty acid β-oxidation process. Together with altered glucose uptake, as revealed by PET-CT, changes in ATP content and mitochondrial structure further verified a metabolic difference related to energy among rats transplanted with the gut microbiota from donors of different ages. This study demonstrated that gut microbes may participate in the physiological aging process of the rat heart by regulating oxidative stress and autophagy. The gut microbiota has been shown to be involved in the natural aging of the heart at multiple levels, from the organ level to the metabolically plastic myocardiocytes and associated molecules.}, }
@article {pmid40116713, year = {2025}, author = {Chinna Meyyappan, A and Sgarbossa, C and Bromley, H and Forth, E and Müller, DJ and Vazquez, G and Cabrera, C and Milev, R}, title = {The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression - A Phase 2, Double-Blind, Placebo-Controlled Study: Clinical Results: Innocuité et efficacité du traitement de l'écosystème microbien (met-2) dans la dépression majeure - une étude de phase 2 à double insu contrölée par placebo : résultats cliniques.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437251328270}, pmid = {40116713}, issn = {1497-0015}, abstract = {ObjectivesThis study examines the safety and efficacy of a fecal transplant alternative, Microbial Ecosystem Therapeutic-2 (MET-2), in improving symptoms of depression. The primary objective of this study is to assess changes in depressive symptoms before, during, and after administration of MET-2 in comparison to placebo. Mood-related symptoms such as anxiety and anhedonia, gastrointestinal symptoms, and safety of the therapeutic were also assessed using both self-report and clinician-rated measures.MethodsTwenty-nine participants (n = 29) experiencing a major depressive episode were recruited from the Kingston and Toronto areas. Participants orally consumed MET-2, an encapsulated microbial therapeutic containing 40 different strains of bacteria, or placebo alternative, once daily for 6 weeks with a 2-week follow-up. Participants underwent a series of clinical assessments used to measure mood, anxiety, and gastrointestinal symptoms.ResultsThere was a significant improvement in depressive symptomology over time as determined by Montgomery-Åsberg Depression Rating Scale scores (p < 0.0001); however there was no significant difference between placebo and MET-2 groups (p = 0.338). No serious adverse events were reported. The findings of this study are the first to provide evidence for the role of oral microbial therapeutics, such as MET-2, as treatment for symptoms of depression.ConclusionsThough there are positive trends suggesting a greater improvement in depressive symptomology among the MET-2 group compared to the placebo group, a larger sample size is needed for more conclusive results. Clinicaltrials.gov NCT04602715.}, }
@article {pmid40116683, year = {2025}, author = {Prati, D and Caprioli, F and Stea, L and Berzuini, A and Pizzotti, D and Petrillo, E and Coluccio, E and Erba, E and Lamorte, G and Ferrari, F and Cariani, L and Amoroso, C and Preti, AC and Bandera, A and Callegaro, A and Castaldi, S and Cardillo, M and Vecchi, M and Valenti, L and De Angelis, V}, title = {A "movement" worth making: why and how Transfusion Services can play a role in Fecal Microbiota Transplant programs.}, journal = {Blood transfusion = Trasfusione del sangue}, volume = {}, number = {}, pages = {}, doi = {10.2450/BloodTransfus.929}, pmid = {40116683}, issn = {2385-2070}, abstract = {Fecal Microbiota Transplantation (FMT) is an innovative therapy with growing applications, particularly for recurrent Clostridioides difficile infections (rCDI). However, the broader use of FMT is challenged by the complexities of donor recruitment, the necessity of stringent screening protocols, and the need for maintaining high-quality stool biobanks. This paper explores the integration of FMT programs within transfusion medicine departments, taking advantage of their expertise in donor management and biological material processing. Despite the complexities of donor screening, including a low eligibility rate, the collaboration between transfusion services and other hospital departments demonstrates a viable model for expanding FMT access. Additionally, the recent EU regulations on substances of human origin (SoHO) offer a framework for standardizing and scaling stool banking, enhancing the safety and efficacy of FMT procedures.}, }
@article {pmid40116376, year = {2025}, author = {Yang, Y and Zhang, Y and Zhang, W and Lu, K and Wang, L and Liu, Y and Du, L and Yang, J and Guan, L and Ma, H}, title = {Flammulina velutipes residue Polysaccharide Alleviates Immunosuppression and Intestinal Injury by Modulating Gut Microbiota and Associated Metabolites.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {13}, pages = {7788-7806}, doi = {10.1021/acs.jafc.4c12105}, pmid = {40116376}, issn = {1520-5118}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Flammulina/chemistry/immunology ; Mice ; Male ; *Polysaccharides/pharmacology/chemistry/administration &amp; dosage ; *Intestines/microbiology/immunology/drug effects ; Humans ; *Cyclophosphamide/adverse effects ; Bacteria/classification/genetics/isolation &amp; purification/drug effects/metabolism ; Mice, Inbred C57BL ; Intestinal Mucosa/immunology/metabolism/drug effects/microbiology ; Immunosuppression Therapy ; Intestinal Diseases/immunology/microbiology/drug therapy/metabolism ; }, abstract = {This study elucidated the mechanisms underlying the immunoregulatory and gut-microbiota-modulating effects of Flammulina velutipes residue polysaccharide (FVRP) using cyclophosphamide (CTX)-induced mouse models. FVRP supplementation alleviated CTX-induced intestinal damage and boosted antioxidant enzyme activity and cytokine secretion. Additionally, FVRP enhanced the diversity and total species richness of the gut microbiota, promoting the proliferation of beneficial bacteria (e.g., Prevotellaceae), while reducing the abundance of CTX-derived bacteria (Lachnospiraceae and Rikenellaceae). FVRP facilitates the accumulation of short-chain fatty acids. Untargeted metabolomic analyses of cecal content revealed that FVRP treatment notably restored the levels of 32 endogenous metabolites altered by CTX. Based on a pseudosterility mice model, fecal microbiota transplantation (FMT), and fecal filtrate transplantation (FFT), gut microbiota and associated metabolites were demonstrated to play a crucial role in the immunomodulatory and protective effects of FVRP against intestinal injury. In conclusion, FVRP exhibits significant potential as an immune enhancer and natural therapeutic agent for alleviating intestinal inflammatory conditions.}, }
@article {pmid40115610, year = {2025}, author = {Waterman, A and Doumas, SA and Fischer, M and Mattar, M and Charbel, S and Jennings, J and Doman, DB}, title = {Uncovering the Hidden Link Between the Aberrant Intestinal Microbiome and Fibromyalgia.}, journal = {Gastroenterology &amp; hepatology}, volume = {21}, number = {2}, pages = {111-121}, pmid = {40115610}, issn = {1554-7914}, abstract = {Fibromyalgia is a multifaceted syndrome primarily characterized by chronic widespread pain and fatigue. Despite its significant prevalence and incidence, the mechanisms mediating the disease pathogenesis have remained poorly understood; however, increasing evidence suggests a potentially central role of intestinal dysbiosis. Researchers have been examining possible diagnostic biomarkers, such as Helicobacter pylori infection, urine metabolite profiles, and cytokine levels, which reflect these microbiome changes. Additionally, evaluation of therapeutic interventions targeting the gut microbiome, including probiotics, fecal microbiota transplantation, and antibiotics for specific infections, has highlighted their potential in alleviating fibromyalgia symptoms. This article delves into the emerging role of the gut microbiome in fibromyalgia pathogenesis, illustrating how alterations in gut bacterial composition and diversity are implicated in the pathophysiology of the disease through the gut-brain axis, and sets a direction for future research to enhance diagnostic accuracy and therapeutic efficacy of this complex condition.}, }
@article {pmid40111698, year = {2025}, author = {Vernon, JJ}, title = {Modulation of the Human Microbiome: Probiotics, Prebiotics, and Microbial Transplants.}, journal = {Advances in experimental medicine and biology}, volume = {1472}, number = {}, pages = {277-294}, pmid = {40111698}, issn = {0065-2598}, mesh = {Humans ; *Prebiotics/administration &amp; dosage ; *Probiotics/therapeutic use ; *Microbiota/physiology ; Mouth/microbiology ; Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation/methods ; }, abstract = {The balance between health and disease is intrinsically linked to the interactions between microbial communities and the host. This complex environment of antagonism and synergy involves both prokaryotic and eukaryotic cells, whose collaborative metabolic pathways and immunomodulatory elements influence system homeostasis. As with the gut and other niches, the oral microbiome has the capacity to affect distal host sites. The ability to manipulate this environment holds the potential to impact local and systemic disease.With the increasing threat of antimicrobial resistance, novel approaches to reduce the burden of disease are essential. The use of probiotics and prebiotics is one such strategy. Probiotics introduce non-pathogenic bacteria into the environment to compete with pathogens for nutrients and attachment sites, or to produce metabolites that counteract disease aetiologies. Prebiotic compounds enhance the growth of health-associated organisms, offering additional benefits, whilst a conjunctive approach with probiotics potentially holds even greater promise. Though widely studied in the gastrointestinal context, their potential for treating oral diseases, such as dental caries and periodontitis, is less understood. Additionally, the use of microbial transplantations has demonstrated efficacy in other areas, reducing systemic inflammation and recolonising with commensal bacteria. Here we evaluate their use in the oral context and their modulatory impact on overall health.In this chapter, we discuss how pro- and prebiotic strategies seek to modulate both the oral and gut environments to promote oral health and prevent disease. We assess novel approaches for utilising health-associated microorganisms to combat oral disorders, either administered locally in the mouth or imparting influence through immune modulation via the oral-gut axis. By examining available clinical trial data, we aim to further understand the intricacies involved in this discipline. Furthermore, we consider the challenges facing the research community, including optimal candidate organism/compound selection and colonisation retention, as well as considerations for future research.}, }
@article {pmid40110391, year = {2025}, author = {Zhu, B and Gu, Z and Hu, H and Huang, J and Zeng, Z and Liang, H and Yuan, Z and Huang, S and Qiu, Y and Sun, XD and Liu, Y}, title = {Altered Gut Microbiota Contributes to Acute-Respiratory-Distress-Syndrome-Related Depression through Microglial Neuroinflammation.}, journal = {Research (Washington, D.C.)}, volume = {8}, number = {}, pages = {0636}, pmid = {40110391}, issn = {2639-5274}, abstract = {Acute respiratory distress syndrome (ARDS) survivors often suffer from long-term psychiatric disorders such as depression, but the underlying mechanisms remain unclear. Here, we found marked alterations in the composition of gut microbiota in both ARDS patients and mouse models. We investigated the role of one of the dramatically changed bacteria-Akkermansia muciniphila (AKK), whose abundance was negatively correlated with depression phenotypes in both ARDS patients and ARDS mouse models. Specifically, while fecal transplantation from ARDS patients into naive mice led to depressive-like behaviors, microglial activation, and intestinal barrier destruction, colonization of AKK or oral administration of its metabolite-propionic acid-alleviated these deficits in ARDS mice. Mechanistically, AKK and propionic acid decreased microglial activation and neuronal inflammation through inhibiting the Toll-like receptor 4/nuclear factor κB signaling pathway. Together, these results reveal a microbiota-dependent mechanism for ARDS-related depression and provide insight for developing a novel preventative strategy for ARDS-related psychiatric symptoms.}, }
@article {pmid40110192, year = {2025}, author = {Zhang, C and Wang, Y and Cheng, L and Cao, X and Liu, C}, title = {Gut microbiota in colorectal cancer: a review of its influence on tumor immune surveillance and therapeutic response.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1557959}, pmid = {40110192}, issn = {2234-943X}, abstract = {Colorectal cancer (CRC) poses a significant global health burden, with gut microbiota emerging as a crucial modulator of CRC pathogenesis and therapeutic outcomes. This review synthesizes current evidence on the influence of gut microbiota on tumor immune surveillance and responses to immunotherapies and chemotherapy in CRC. We highlight the role of specific microbial taxa in promoting or inhibiting tumor growth and the potential of microbiota-based biomarkers for predicting treatment efficacy. The review also discusses the implications of microbiota modulation strategies, including diet, probiotics, and fecal microbiota transplantation, for personalized CRC management. By critically evaluating the literature, we aim to provide a comprehensive understanding of the gut microbiota's dual role in CRC and to inform future research directions in this field.}, }
@article {pmid40110027, year = {2025}, author = {Cai, S and Li, Z and Bai, J and Ding, Y and Liu, R and Fang, L and Hou, D and Zhang, S and Wang, X and Wang, Y and Jiang, Y and Xiang, Y and Wu, W and He, Y and Zhang, Y and Ren, X}, title = {Optimized oxygen therapy improves sleep deprivation-induced cardiac dysfunction through gut microbiota.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1522431}, pmid = {40110027}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Sleep Deprivation ; Mice ; *Fecal Microbiota Transplantation ; *RNA, Ribosomal, 16S/genetics ; *Disease Models, Animal ; Male ; Fibrosis ; Mice, Inbred C57BL ; Heart Diseases/therapy/microbiology ; Oxygen Inhalation Therapy/methods ; Oxygen/metabolism ; }, abstract = {Adequate sleep is of paramount importance for relieving stress and restoring mental vigor. However, the adverse physiological and pathological responses resulting from sleep insufficiency or sleep deprivation (SD) are becoming increasingly prevalent. Currently, the impact of sleep deficiency on gut microbiota and microbiota-associated human diseases, especially cardiac diseases, remains controversial. Here, we employed the following methods: constructed an experimental sleep-deprivation model in mice; conducted 16S rRNA sequencing to investigate the changes in gut microbiota; through fecal microbiota transplantation (FMT) experiments, transplanted fecal microbiota from sleep-deprived mice to other mice; established an environment with a 30% oxygen concentration to explore the therapeutic effects of oxygen therapy on gut microbiota-associated cardiac fibrosis and dysfunction; and utilized transcriptome data to study the underlying mechanisms of oxygen therapy. The results revealed that: sleep-deprived mice exhibited weakness, depression-like behaviors, and dysfunction in multiple organs. Pathogenic cardiac hypertrophy and fibrosis occurred in sleep-deprived mice, accompanied by poor ejection fraction and fractional shortening. 16S rRNA sequencing indicated that sleep deprivation induced pathogenic effects on gut microbiota, and similar phenomena were also observed in mice that received fecal microbiota from sleep-deprived mice in the FMT experiments. The environment with a 30% oxygen concentration effectively alleviated the pathological impacts on cardiac function. Transcriptome data showed that oxygen therapy targeted several hypoxia-dependent pathways and inhibited the production of cardiac collagen. In conclusion, these results demonstrate the significance of sufficient sleep for gut microbiota and may represent a potential therapeutic strategy, where the oxygen environment exerts a protective effect on insomniacs through gut microbiota.}, }
@article {pmid40107339, year = {2025}, author = {Xue, M and Deng, Q and Deng, L and Xun, T and Huang, T and Zhao, J and Wei, S and Zhao, C and Chen, X and Zhou, Y and Liang, Y and Yang, X}, title = {Alterations of gut microbiota for the onset and treatment of psoriasis: A systematic review.}, journal = {European journal of pharmacology}, volume = {998}, number = {}, pages = {177521}, doi = {10.1016/j.ejphar.2025.177521}, pmid = {40107339}, issn = {1879-0712}, abstract = {Psoriasis is a chronic, recurrent and systemic inflammatory skin disease which is mediated by immunoreaction. Its pathogenesis is multifactorial, and the exact driving factor remains unclear. Recent studies showed that gut microbiota, which maintain immune homeostasis of our bodies, is closely related with occurrence, development and prognosis of psoriasis. The intestinal microbial abundance and diversity in patients with psoriasis have changed significantly, including intestinal microbiota disorders and reduced production of short chain fatty acids (SCFAs), abnormalities in Firmicutes/Bacteroidetes (F/B), etc. Besides, the intestinal microbiota of psoriasis patients has also changed after treatment of systemic drugs, biologics and small molecule chemical drugs, suggesting that the intestinal microbiota may be a potential response-to-treatment biomarker for evaluating treatment effectiveness. Oral probiotics and prebiotics administration as well as fecal microbial transplantation were also reported to benefit well in psoriasis patients. Additionally, we also discussed the microbial changes from the skin and other organs, which regulated both the onset and treatment of psoriasis together with gut microbiota. Herein, we reviewed recent studies on the psoriasis-related microbiota in an attempt to confidently identify the "core" microbiota of psoriatic patients, understand how microbiota influence psoriasis through the gut-skin axis, and explore potential therapeutic strategies for psoriasis.}, }
@article {pmid40104324, year = {2025}, author = {Gu, C and Sha, G and Zeng, B and Cao, H and Cao, Y and Tang, D}, title = {Therapeutic potential of fecal microbiota transplantation in colorectal cancer based on gut microbiota regulation: from pathogenesis to efficacy.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251327167}, pmid = {40104324}, issn = {1756-283X}, abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with its progression intricately linked to gut microbiota dysbiosis. Disruptions in microbial homeostasis contribute to tumor initiation, immune suppression, and inflammation, establishing the microbiota as a key therapeutic target. Fecal microbiota transplantation (FMT) has emerged as a transformative approach to restore microbial balance, enhance immune responses, and reshape the tumor microenvironment. This review explores the mechanisms underlying FMT's therapeutic potential, evaluates its advantages over other microbiota-based interventions, and addresses challenges such as donor selection, safety concerns, and treatment standardization. Looking forward, the integration of FMT into personalized CRC therapies requires robust clinical trials and the identification of predictive biomarkers to optimize its efficacy and safety.}, }
@article {pmid40104059, year = {2025}, author = {Sharma, P and Jain, T and Sorgen, A and Iyer, S and Tarique, M and Roy, P and Kurtom, S and Sethi, V and Bava, EP and Gutierrez-Garcia, AK and Vaish, U and Suresh, DS and Sahay, P and Edwards, D and Afghani, J and Putluri, S and Reddy, KRK and Amara, CS and Kamal, AHM and Fodor, A and Dudeja, V}, title = {Smoking-induced gut microbial dysbiosis mediates cancer progression through modulation of anti-tumor immune response.}, journal = {iScience}, volume = {28}, number = {3}, pages = {112002}, pmid = {40104059}, issn = {2589-0042}, abstract = {Cigarette smoke exposure (CSE) increases the risk for a plethora of cancers. Recent evidence indicates that the gut microbiome can influence cancer progression by immune system modulation. Since CSE alters the gut microbiome, we hypothesized that the gut microbiome serves as a causative link between smoking and cancer growth. Through a combination of syngeneic animal models and fecal microbiota transplantation studies, we established an essential role for smoke-induced dysbiosis in cancer growth. 16s rRNA sequencing and liquid chromatography-mass spectrometry indicated a unique CSE-associated microbial and metabolomic signature. Immunophenotyping of tumor specimens and experiments in Rag1-KO and CD8-KO demonstrated that smoke-induced tumor growth requires functional adaptive immunity. Finally, utilizing gut microbial ablation strategies with broad- and narrow-spectrum antibiotics, we demonstrated the reversal of phenotypic effects of CSE. Our study provides evidence for gut microbiome as an actionable target to mitigate CSE-induced tumor promotion.}, }
@article {pmid40103733, year = {2025}, author = {Hirsch, W and Fischer, M and Khoruts, A and Allegretti, JR and Kelly, CR and Vaughn, B}, title = {Risk Factors for Antibiotic Exposure Post-Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection: A Prospective Multicenter Observational Study.}, journal = {Open forum infectious diseases}, volume = {12}, number = {3}, pages = {ofaf130}, pmid = {40103733}, issn = {2328-8957}, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (CDI) is primarily driven by antibiotic-induced disruption of the indigenous intestinal microbiota. Restoration of microbiota through fecal microbiota transplantation (FMT) is effective in preventing subsequent CDI, although this effect is attenuated with additional antibiotic exposure. The aim of this study was to identify the risk factors for recurrent antibiotic administration after FMT.<br><br>METHODS: This is a prospective cohort of patients who were administered FMT for recurrent CDI from 1 July 2019 through 23 November 2023 across 6 institutions in the United States. Providers collected de-identified data at the time of FMT administration and in the months post-FMT administration.<br><br>RESULTS: The analysis included 448 patients. Risk factors for non-CDI antibiotic administration within 2 months of FMT included immunocompromised status (odds ratio [OR], 2.2 [95% confidence interval {CI}, 1.1-4.4]; P = .02), >3 non-CDI antibiotic courses pre-FMT (OR, 3.1 [95% CI, 1.4-6.8]; P = .006), and prior hospitalization for CDI (OR, 2.0 [95% CI, 1.1-3.8]; P = .02). The most common indications for non-CDI antibiotic administration post-FMT were urinary tract infections, respiratory infections, and procedure prophylaxis.<br><br>CONCLUSIONS: Non-CDI antibiotic exposure significantly increases the risk of CDI recurrence post-FMT. Risk factors for non-CDI antibiotic administration within 2 months of FMT include immunocompromised status, multiple prior non-CDI antibiotics, and prior hospitalization for CDI. These individuals may benefit from additional or modified recurrent CDI prevention strategies.}, }
@article {pmid40099491, year = {2025}, author = {Deng, Z and Mei, S and Ouyang, Z and Wang, R and Wang, L and Zou, B and Dai, J and Mao, K and Li, Q and Guo, Q and Yi, C and Meng, F and Xie, M and Zhang, X and Wang, R and Deng, T and Wang, Z and Li, X and Wang, Q and Liu, B and Tian, X}, title = {Dysregulation of gut microbiota stimulates NETs-driven HCC intrahepatic metastasis: therapeutic implications of healthy faecal microbiota transplantation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2476561}, pmid = {40099491}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation ; Animals ; *Gastrointestinal Microbiome ; *Carcinoma, Hepatocellular/therapy/microbiology/pathology ; Humans ; *Liver Neoplasms/therapy/microbiology/pathology ; Mice ; *Extracellular Traps/metabolism ; Male ; Bacteria/classification/genetics/isolation &amp; purification ; Female ; Middle Aged ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Disease Models, Animal ; }, abstract = {The stringent regulation of intrahepatic metastases is essential for improving survival outcomes in patients with hepatocellular carcinoma (HCC). This study investigated the impact of gut microbiota on intrahepatic metastasis of HCC and evaluated the therapeutic potential of healthy fecal microbiota transplantation (FMT). Dysregulation of the gut microbiota, characterized by a significant reduction in the abundance of beneficial bacteria, such as Anaerotruncus colihominis and Dysosmobacter welbionis, was observed in patients with intrahepatic metastatic HCC. A human flora-associated (HFA) intrahepatic metastatic HCC mouse model was successfully established through consecutive 4 weeks of human-mouse FMT. Dysregulation of gut microbiota promoted intrahepatic metastasis in the mouse model, primarily by enhancing neutrophil-mediated inflammatory responses and lead to excessive formation of neutrophil extracellular traps (NETs). Consequently, it promoted tumor vascular growth and tissue necrosis, resulting in intrahepatic metastasis of HCC. Notably, FMT from healthy donors mitigated these pathological processes. This study elucidated the role and mechanism of dysregulated gut microbiota in promoting intrahepatic metastasis of HCC. Healthy FMT emerges as a promising novel therapeutic strategy for preventing and treating intrahepatic metastasis of HCC.}, }
@article {pmid40098090, year = {2025}, author = {Xiao, P and Li, Y and Li, X and Ge, T and Li, D and Xu, Q and Ruan, Y and Xiao, F and Xiao, Y and Zhang, T}, title = {Long-term safety of fecal microbiota transplantation in Chinese children from 2013 to 2023: a single-center retrospective study.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {152}, pmid = {40098090}, issn = {1471-2180}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Fecal Microbiota Transplantation/methods/adverse effects ; Child ; Child, Preschool ; China ; Adolescent ; Infant ; *Gastrointestinal Microbiome ; Treatment Outcome ; Feces/microbiology ; East Asian People ; }, abstract = {BACKGROUND: The gut microbiome plays a vital role in influencing various health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a rapid, safe, and effective method for modifying the microbiome. However, there is a lack of long-term safety data regarding FMT in children. This study presents the largest single-center analysis of the long-term safety outcomes of FMT in pediatric patients in China, featuring a substantial sample size and an extended follow-up period to thoroughly examine its safety in children.<br><br>METHODS: A retrospective study was conducted on 813 patients who underwent FMT treatments at our hospital from December 2013 to December 2023. All FMT procedures adhered to standardized protocols. The safety of these treatments was retrospectively assessed, focusing on adverse events (AEs) and serious adverse events (SAEs). AEs associated with FMT were categorized as short-term (within 48 h post-FMT) and long-term (within 3 months). Various potential influencing factors for AEs, including sex, age, route of administration, disease type, and consanguineous donor, were examined as independent variables. Significant independent factors and their associated risk ratios with 95% confidence intervals (CI) were determined through multivariate logistic regression analysis. A p-value of less than 0.05 was considered statistically significant.<br><br>RESULTS: A total of 813 patients underwent FMT, with a median age of 93 months (range 4-215) and 68.0% being males. The average follow-up time was 32.3 months (range 1-122). All short-term AEs resolved within 48&#xa0;h, with an overall occurrence rate of 5.8% (47/813). The most common short-term AEs included vomiting (2.0%), abdominal pain (1.6%), diarrhea (0.9%), fever (0.7%), dysphoria (0.4%), and nausea (0.4%). Multivariable analysis revealed that patients with inflammatory bowel disease (IBD) (OR: 3.98, 95% CI: 1.78-8.92, P&#x2009;=&#x2009;0.001) and those who received FMT via capsules (OR: 0.09, 95% CI: 0.03-0.27, P&#x2009;=&#x2009;0.000) were independent risk factors for FMT-related AEs. All 813 patients were followed up for at least 1 month, with 78.8% followed for more than 12 months. No long-term AEs occurred during the longest follow-up period of 122 months.<br><br>CONCLUSIONS: FMT is a promising treatment option that appears to be safe and well tolerated. This study stands out for its substantial sample size, making it's the largest reported series in pediatrics, as well as for having the longest follow-up period for FMT in this population.<br><br>CLINICAL TRIAL NUMBER: Not applicable.}, }
@article {pmid40098052, year = {2025}, author = {Oami, T and Shimazui, T and Yumoto, T and Otani, S and Hayashi, Y and Coopersmith, CM}, title = {Gut integrity in intensive care: alterations in host permeability and the microbiome as potential therapeutic targets.}, journal = {Journal of intensive care}, volume = {13}, number = {1}, pages = {16}, pmid = {40098052}, issn = {2052-0492}, support = {R35 GM148217/GM/NIGMS NIH HHS/United States ; GM148217//Foundation for the National Institutes of Health/ ; }, abstract = {BACKGROUND: The gut has long been hypothesized to be the "motor" of critical illness, propagating inflammation and playing a key role in multiple organ dysfunction. However, the exact mechanisms through which impaired gut integrity potentially contribute to worsened clinical outcome remain to be elucidated. Critical elements of gut dysregulation including intestinal hyperpermeability and a perturbed microbiome are now recognized as potential therapeutic targets in critical care.<br><br>MAIN BODY: The gut is a finely tuned ecosystem comprising ~&#xa0;40 trillion microorganisms, a single cell layer intestinal epithelia that separates the host from the microbiome and its products, and the mucosal immune system that actively communicates in a bidirectional manner. Under basal conditions, these elements cooperate to maintain a finely balanced homeostasis benefitting both the host and its internal microbial community. Tight junctions between adjacent epithelial cells selectively transport essential molecules while preventing translocation of pathogens. However, critical illness disrupts gut barrier function leading to increased gut permeability, epithelial apoptosis, and immune activation. This disruption is further exacerbated by a shift in the microbiome toward a "pathobiome" dominated by pathogenic microbes with increased expression of virulence factors, which intensifies systemic inflammation and accelerates organ dysfunction. Research has highlighted several potential therapeutic targets to restore gut integrity in the host, including the regulation of epithelial cell function, modulation of tight junction proteins, and inhibition of epithelial apoptosis. Additionally, microbiome-targeted therapies, such as prebiotics, probiotics, fecal microbiota transplantation, and selective decontamination of the digestive tract have also been extensively investigated to promote restoration of gut homeostasis in critically ill patients. Future research is needed to validate the potential efficacy of these interventions in clinical settings and to determine if the gut can be targeted in an individualized fashion.<br><br>CONCLUSION: Increased gut permeability and a disrupted microbiome are common in critical illness, potentially driving dysregulated systemic inflammation and organ dysfunction. Therapeutic strategies to modulate gut permeability and restore the composition of microbiome hold promise as novel treatments for critically ill patients.}, }
@article {pmid40097405, year = {2025}, author = {Li, L and Li, T and Liang, X and Zhu, L and Fang, Y and Dong, L and Zheng, Y and Xu, X and Li, M and Cai, T and Zhao, F and Xin, M and Shao, M and Guan, Y and Liu, M and Li, F and Zhang, C and Wang, Q and Sun, W and Zheng, Y}, title = {A decrease in Flavonifractor plautii and its product, phytosphingosine, predisposes individuals with phlegm-dampness constitution to metabolic disorders.}, journal = {Cell discovery}, volume = {11}, number = {1}, pages = {25}, pmid = {40097405}, issn = {2056-5968}, support = {2023T160729//China Postdoctoral Science Foundation/ ; }, abstract = {According to traditional Chinese medicine (TCM) constitutional theory, individuals with phlegm-dampness constitution (PDC) are at increased risk for metabolic disorders. Previous studies have indicated that PDC individuals exhibit gene expression changes associated with metabolic disorders, even individuals with normal metabolic indices. However, the biological mechanisms underlying these changes remain unclear. The gut microbiota has recently emerged as a promising avenue for elucidating TCM principles. Here, we revealed that individuals with PDC have distinct gut microbiota and serum metabolite profiles. A decrease in phytosphingosine was associated with increased PDC scores and metabolic disorder severity. Subsequent experiments demonstrated that Flavonifractor plautii can biosynthesize phytosphingosine, which was also negatively correlated with the PDC score. Interestingly, both F. plautii and phytosphingosine levels decreased in PDC subjects with normal metabolic indices. Fecal transplantation from these individuals accelerated the development of metabolic disorders in mice. However, supplementation with F. plautii and phytosphingosine ameliorated metabolic disorders by increasing phytosphingosine levels in the gut‒hepatic axis. Mechanistic investigations confirmed that phytosphingosine can directly bind to hepatic peroxisome proliferator-activated receptor α (PPARα) and activate its nuclear transcription activity, thereby regulating downstream gene expression related to glucose‒lipid metabolism. Our research indicates that the decrease in F. plautii and its product, phytosphingosine, contributes to gene expression changes related to metabolic disorders in PDC individuals and increases their susceptibility to metabolic disorders. These findings suggest that diagnosing PDC may be beneficial for identifying at-risk populations among apparently healthy individuals, thereby advancing the broader field of metabolic disorder prevention and TCM integration.}, }
@article {pmid40096354, year = {2025}, author = {Dongre, DS and Saha, UB and Saroj, SD}, title = {Exploring the role of gut microbiota in antibiotic resistance and prevention.}, journal = {Annals of medicine}, volume = {57}, number = {1}, pages = {2478317}, pmid = {40096354}, issn = {1365-2060}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; *Dysbiosis/microbiology ; Drug Resistance, Multiple, Bacterial/genetics ; Fecal Microbiota Transplantation ; Drug Resistance, Microbial/genetics ; Bacteria/drug effects/genetics ; Probiotics/administration &amp; dosage/therapeutic use ; }, abstract = {BACKGROUND/INTRODUCTION: Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is of grave public health concern. To combat the pandemic of AMR, it is necessary to focus on novel alternatives for drug development. Within the host, the interaction of the pathogen with the microbiome plays a pivotal role in determining the outcome of pathogenesis. Therefore, microbiome-pathogen interaction is one of the potential targets to be explored for novel antimicrobials.<br><br>MAIN BODY: This review focuses on how the gut microbiome has evolved as a significant component of the resistome as a source of antibiotic resistance genes (ARGs). Antibiotics alter the composition of the native microbiota of the host by favouring resistant bacteria that can manifest as opportunistic infections. Furthermore, gut dysbiosis has also been linked to low-dosage antibiotic ingestion or subtherapeutic antibiotic treatment (STAT) from food and the environment.<br><br>DISCUSSION: Colonization by MDR bacteria is potentially acquired and maintained in the gut microbiota. Therefore, it is pivotal to understand microbial diversity and its role in adapting pathogens to AMR. Implementing several strategies to prevent or treat dysbiosis is necessary, including faecal microbiota transplantation, probiotics and prebiotics, phage therapy, drug delivery models, and antimicrobial stewardship regulation.}, }
@article {pmid40095949, year = {2025}, author = {Newsome, RC and McGriff, C and Gharaibeh, RZ and Jobin, C}, title = {Preparation and Maintenance of Bioexclusion IsoPositive Cage Experiment for Human Fecal Transplantation into Germ-Free Mice.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {216}, pages = {}, doi = {10.3791/68029}, pmid = {40095949}, issn = {1940-087X}, mesh = {Animals ; Mice ; Humans ; *Fecal Microbiota Transplantation/methods ; *Germ-Free Life ; Feces/microbiology ; Housing, Animal ; Animal Husbandry/methods ; }, abstract = {Germ-free mice are an important investigation tool for understanding the contribution of microorganisms in host health and disease, enabling assessment of the specific role of individuals, defined or complex groups of microorganisms in host response. Traditionally bred and reared in flexible-film or semi-rigid isolators, germ-free mouse husbandry and experimental manipulation are costly and require numerous trained staff and a large space footprint in animal housing facilities. The IsoPositive caging system allows for experimental manipulation of germ-free mice in individual, hermetically-sealed, positive-pressure isolator cages (isocages), reducing cost and enabling greater flexibility in experimental manipulations. Here, a protocol is described for transferring germ-free mice from breeding isolators to isocages and subsequent fecal transfer from human donor stool into mice to create stable long-term gut "humanized" mice for future studies. The materials and preparation needed for the utilization of the isocage system are described, including the use of chlorine-dioxide sterilant chemical sterilant to clean cages, supplies, equipment, and personal protective equipment. The methods for confirming the germ-free status of transferred mice and how to determine contamination in the caging system are discussed. The procedure for husbandry, including bedding, food, and water supply, is further discussed. The protocol for human fecal slurry preparation and gavage into germ-free mice to create gut "humanized" mice, along with stool collection to monitor the microbial community composition of these mice, are described. An experiment illustrates that two weeks post-human fecal transplant allows for stable colonization of donor microbiota in the murine hosts, enabling subsequent experimental usage. Furthermore, the collection of humanized mouse feces in viability preservation media, enabling use in further functional experiments, is described. Overall, these methods allow for the safe and effective establishment of humanized mouse communities in experimental gnotobiotic cages for further manipulation.}, }
@article {pmid40094148, year = {2025}, author = {Wang, X and Wang, WY and Yu, XL and Chen, JW and Yang, JS and Wang, MK}, title = {Comprehensive review of Clostridium difficile infection: Epidemiology, diagnosis, prevention, and treatment.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {16}, number = {1}, pages = {100560}, pmid = {40094148}, issn = {2150-5349}, abstract = {In recent years, nosocomial infections caused by Clostridium difficile (C. difficile) have risen, becoming a leading cause of hospital-acquired diarrhea. The global prevalence of C. difficile infection (CDI) varies across regions and populations. The diagnosis relies primarily on laboratory testing, including toxin, glutamate dehydrogenase, and nucleic acid amplification tests. Treatment strategies for CDI include antimicrobial therapy (e.g., metronidazole, vancomycin, and fidamycin), fecal transplantation, and immunotherapy (e.g., belotozumab), depending on the patient's specificity and severity. This paper reviews recent research on CDI's epidemiological characteristics, risk factors, diagnosis, treatment, and prevention, aiming to support hospitals and public health initiatives in implementing effective detection, prevention, and treatment strategies.}, }
@article {pmid40091757, year = {2025}, author = {Le, PH and Chen, CL and Kuo, CJ and Yeh, PJ and Chen, CC and Chen, YC and Chiu, CT and Cheng, HT and Tsou, YK and Pan, YB and Chiu, CH}, title = {Impact of Clostridioides difficile Infection on Clinical Outcomes in Hospitalized IBD Patients and the Role of Fecal Microbiota Transplantation: A Retrospective Cohort Study.}, journal = {The Kaohsiung journal of medical sciences}, volume = {}, number = {}, pages = {e70002}, doi = {10.1002/kjm2.70002}, pmid = {40091757}, issn = {2410-8650}, support = {MOHW113-TDU-B-212-114010//Ministry of Health and Welfare (Taiwan)/ ; }, abstract = {Clostridioides difficile infection (CDI) worsens the prognosis of patients with inflammatory bowel disease (IBD). This retrospective cohort study aimed to evaluate the risk factors, clinical manifestations, and outcomes of CDI in hospitalized patients with IBD, including those with toxin A/B results between April 2007 and April 2021. Patients were classified into the CDI and control groups. Patients with IBD and recurrent or refractory CDI underwent fecal microbiota transplantation (FMT). A total of 144 inpatients with IBD-45 in the CDI group and 99 in the control group-were analyzed. The incidence of CDI in inpatients with IBD was 31%. The Risk factors for CDI included longer IBD duration, biological therapy failure, and biological use. More patients in the CDI group presented with abdominal pain (77.8% vs. 55.6%, p = 0.011). In the antibiotic treatment-only group, the symptom improvement rate was 60.7% (17/28), the microbiological cure rate was 89.3% (25/28), and the overall success rate was 71.4% (20/28). After antibiotic treatment and FMT, 71.4% (10/14) of the patients tested negative for CDI, and 64.3% (9/14) had improved clinical symptoms. CDI led to more hospitalizations (median two times [range 0-12] vs. median one time [range 0-19], p = 0.008), a lower steroid-free remission rate (46.7% vs. 67.7%, p = 0.017), and higher Mayo scores (median 5 points [range 2-12] vs. median 3 points [range 0-12]). Patients who received FMT had fewer hospitalizations and fewer IBD-related complications during follow-up than those who received antibiotics alone. FMT should be considered in patients with IBD with refractory or recurrent CDI to improve clinical outcomes.}, }
@article {pmid40091072, year = {2025}, author = {Liu, Y and Liu, J and Ren, R and Xin, Z and Luo, Y and Chen, Y and Huang, C and Liu, Y and Yang, T and Wang, X}, title = {Short-term and long-term high-fat diet promote metabolic disorder through reprogramming mRNA m[6]A in white adipose tissue by gut microbiota.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {75}, pmid = {40091072}, issn = {2049-2618}, support = {32330098//National Natural Science Foundation of China/ ; 2022R52023//Science and technology innovation leading talent project of Zhejiang Province/ ; 2023YFD1301303//National Key Research and Development Program of China/ ; }, mesh = {*Gastrointestinal Microbiome ; *Diet, High-Fat/adverse effects ; Animals ; *Adipose Tissue, White/metabolism ; Mice ; Male ; *Metabolic Diseases/metabolism/microbiology/genetics ; *RNA, Messenger/genetics/metabolism ; *Mice, Inbred C57BL ; Endogenous Retroviruses/genetics ; Fecal Microbiota Transplantation ; Long Interspersed Nucleotide Elements/genetics ; Epigenesis, Genetic ; Adenosine/analogs &amp; derivatives ; }, abstract = {BACKGROUND: Although short-term high-fat diet (S-HFD) and long-term high-fat diet (L-HFD) induce metabolic disorder, the underlying epigenetic mechanism is still unclear.<br><br>RESULTS: Here, we found that both 4&#xa0;days of S-HFD and 10&#xa0;weeks of L-HFD increased mRNA m[6]A level in epididymal white adipose tissue (eWAT) and impaired metabolic health. Interestingly, S-HFD activated transposable elements (TEs), especially endogenous retroviruses (ERVs) in eWAT, while L-HFD activated long interspersed elements (LINEs). Subsequently, we demonstrated that both S-HFD and L-HFD increased m[6]A level of Ehmt2 and decreased EHMT2 protein expression and H3K9me2 level, accounting for activation of ERVs and LINEs. Overexpression of EHMT2 in eWAT or inhibition of ERVs and LINEs by antiviral therapy improved metabolic health under HFD feeding. Notably, we found that both short-term and long-term HFD feeding increased Fimicutes/Bacteroidota ratio and decreased the gut microbiome health index. Fecal microbiota transplantation (FMT) experiments demonstrated that gut microbiota from S-HFD and L-HFD was responsible for increased m[6]A level in eWAT, resulting in glucose intolerance and insulin insensitivity. Furthermore, we identified that both S-HFD and L-HFD increased the abundance of the gut microbial metabolite homogentisic acid (HGA), and HGA level was positively correlated with unclassified_f__Lachnospiraceae which was both increased in S-HFD and L-HFD feeding mice. Administration of HGA increased the m[6]A level of Ehmt2 and decreased the EHMT2 protein expression and H3K9me2 level in eWAT, leading to metabolic disorder in mice.<br><br>CONCLUSIONS: Together, this study reveals a novel mechanism that S-HFD and L-HFD induce metabolism disorder through gut microbiota-HGA-m[6]A-Ehmt2-ERV/LINE signaling. These findings may provide a novel insight for prevention and treatment of metabolism disorder upon short-term or long-term dietary fat intake. Video Abstract.}, }
@article {pmid40089059, year = {2025}, author = {Fan, J and Wu, Y and Wang, X and Ullah, H and Ling, Z and Liu, P and Wang, Y and Feng, P and Ji, J and Li, X}, title = {The probiotic enhances donor microbiota stability and improves the efficacy of fecal microbiota transplantation for treating colitis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.03.017}, pmid = {40089059}, issn = {2090-1224}, abstract = {INTRODUCTION: The stability and metabolic functionality of donor microbiota are critical determinants of fecal microbiota transplantation (FMT) efficacy in inflammatory bowel disease (IBD). While probiotics show potential to enhance microbiota resilience, their role in optimizing donor microbiota for FMT remains underexplored.<br><br>OBJECTIVES: This study investigated whether pretreatment of donor microbiota with L. plantarum GR-4 could improve FMT outcomes in a DSS-induced colitis model by modulating microbial stability, metabolic activity, and host-microbiome interactions.<br><br>METHODS: Donor mice received L. plantarum GR-4 for 3&#xa0;weeks to generate modified FMT (MFMT). DSS-colitis mice were treated with MFMT, conventional FMT, or 5-aminosalicylic acid (5-ASA). Multi-omics analyses and functional assays (stress resistance, engraftment efficiency) were used to evaluate therapeutic mechanisms.<br><br>RESULTS: GR-4 pretreatment conferred three key advantages to donor microbiota: Ecological stabilization: 1. GR-4-driven acidification (pH 3.97 vs. 4.59 for LGG, p&#xa0;<&#xa0;0.0001) enriched butyrogenic Butyricicoccus (73&#xa0;% butyrate increase, p&#xa0;<&#xa0;0.05) and improved stress resistance to bile acids/gastric conditions (1.25&#xa0;&#xd7;&#xa0;survival vs. FMT). 2. Metabolic reprogramming: GR-4 metabolized 25.3&#xa0;% of tryptophan (vs. 10.3&#xa0;% for LGG) to generate immunomodulatory indoles (ILA, IAA), activating aryl hydrocarbon receptor (AHR) signaling and upregulating anti-inflammatory IL-10/IL-22. 3. Bile acid remodeling: MFMT restored sulfolithocholic acid and &#x3b2;-MCA levels, outperforming FMT in resolving DSS-induced dysregulation. MFMT achieved an 83&#xa0;% remission rate (vs. 50&#xa0;% for FMT), enhanced gut barrier integrity, and reversed colitis-associated metabolic dysregulation (e.g., elevated spermidine, 7-sulfocholic acid). Probiotic preconditioning improved donor engraftment by 1.25&#xa0;&#xd7;&#xa0;and enriched success-associated taxa (Sporobacter, Butyricimonas), while suppressing pathogens (Clostridium papyrosolvens).<br><br>CONCLUSIONS: L. plantarum GR-4 optimizes donor microbiota via pH-driven niche engineering, immunometabolic reprogramming, and bile acid modulation, addressing key limitations of conventional FMT. The multi-targeted efficacy of MFMT, evidenced by superior remission rates and metabolic restoration, establishes this approach as a translatable strategy for IBD therapy. This study establishes probiotic-enhanced FMT as a paradigm for precision microbiome interventions.}, }
@article {pmid40088964, year = {2025}, author = {Hajjeh, O and Rajab, I and Bdair, M and Saife, S and Zahran, A and Nazzal, I and AbuZahra, MI and Jallad, H and Abukhalil, MM and Hallak, M and Al-Said, OS and Al-Braik, R and Sawaftah, Z and Milhem, F and Almur, O and Saife, S and Aburemaileh, M and Abuhilal, A}, title = {Enteric nervous system dysfunction as a driver of central nervous system disorders: The Forgotten brain in neurological disease.}, journal = {Neuroscience}, volume = {572}, number = {}, pages = {232-247}, doi = {10.1016/j.neuroscience.2025.03.015}, pmid = {40088964}, issn = {1873-7544}, mesh = {Humans ; *Enteric Nervous System/physiopathology ; Animals ; Gastrointestinal Microbiome/physiology ; *Central Nervous System Diseases/physiopathology/therapy ; *Brain/physiopathology ; Brain-Gut Axis/physiology ; }, abstract = {The Enteric Nervous System (ENS), often called the "second brain," is a complex network of neurons and glial cells within the gastrointestinal (GI) tract. It functions autonomously while maintaining close communication with the central nervous system (CNS) via the gut-brain axis (GBA). ENS dysfunction plays a crucial role in neurodegenerative and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Disruptions such as altered neurotransmission, gut microbiota imbalance, and neuroinflammation contribute to disease pathogenesis. The GBA enables bidirectional communication through the vagus nerve, gut hormones, immune signaling, and microbial metabolites, linking gut health to neurological function. ENS dysregulation is implicated in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), influencing systemic and CNS pathology through neuroinflammation and impaired barrier integrity. This review highlights emerging therapeutic strategies targeting ENS dysfunction, including prebiotics, probiotics, fecal microbiota transplantation (FMT), and vagus nerve stimulation, which offer novel ways to modulate gut-brain interactions. Unlike previous perspectives that view the ENS as a passive disease marker, this review repositions it as an active driver of neurological disorders. By integrating advances in ENS biomarkers, therapeutic targets, and GBA modulation, this article presents a paradigm shift-emphasizing ENS dysfunction as a fundamental mechanism in neurodegeneration and neurodevelopmental disorders. This perspective paves the way for innovative diagnostics, personalized gut-targeted therapies, and a deeper understanding of the ENS's role in brain health and disease.}, }
@article {pmid40087204, year = {2025}, author = {Lin, D and Howard, A and Raihane, AS and Di Napoli, M and Cáceres, E and Ortiz, M and Davis, J and Abdelrahman, AN and Divani, AA}, title = {Traumatic Brain Injury and Gut Microbiome: The Role of the Gut-Brain Axis in Neurodegenerative Processes.}, journal = {Current neurology and neuroscience reports}, volume = {25}, number = {1}, pages = {23}, pmid = {40087204}, issn = {1534-6293}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/microbiology/physiopathology ; *Brain Injuries, Traumatic/microbiology/physiopathology/complications ; *Brain-Gut Axis/physiology ; Animals ; Dysbiosis ; Brain/physiopathology ; }, abstract = {PURPOSE OF REVIEW: A deeper understanding of the communication network between the gut microbiome and the central nervous system, termed the gut-brain axis (GBA), has revealed new potential targets for intervention to prevent the development of neurodegenerative disease associated with tramatic brain injury (TBI). This review aims to comprehensively examine the role of GBA post-traumatic brain injury (TBI).<br><br>RECENT FINDINGS: The GBA functions through neural, metabolic, immune, and endocrine systems, creating bidirectional signaling pathways that modulate brain and gastrointestinal (GI) tract physiology. TBI perturbs these signaling pathways, producing pathophysiological feedback loops in the GBA leading to dysbiosis (i.e., a perturbed gut microbiome, impaired brain-blood barrier, impaired intestinal epithelial barrier (i.e., "leaky gut"), and a maladaptive, systemic inflammatory response. Damage to the CNS associated with TBI leads to GI dysmotility, which promotes small intestinal bacterial overgrowth (SIBO). SIBO has been associated with the early stages of neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Many of the bacteria associated with this overgrowth promote inflammation and, in rodent models, have been shown to compromise the structural integrity of the intestinal mucosal barrier, causing malabsorption of essential nutrients and further exacerbating dysbiosis. TBI-induced pathophysiology is strongly associated with an increased risk of neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, which represents a significant public health burden and challenge for patients and their families. A healthy gut microbiome has been shown to promote improved recovery from TBI and prevent the development of neurodegenerative disease, as well as other chronic complications. The role of the gut microbiome in brain health post-TBI demonstrates the potential for microbiome-targeted interventions to mitigate TBI-associated comorbidities. Promising new evidence on prebiotics, probiotics, diet, and fecal microbiota transplantation may lead to new therapeutic options for improving the quality of life for patients with TBI. Still, many of these preliminary findings must be explored further in clinical settings. This review covers the current understanding of the GBA in the setting of TBI and how the gut microbiome may provide a novel therapeutic target for treatment in this patient population.}, }
@article {pmid40084003, year = {2025}, author = {Oliwa-Libumska, K and Jaworska-Czerwinska, A and Mallek-Grabowska, M and Wlodarski, R and Zuratynski, P and Kozlowski, B}, title = {Fecal microbiota transplantation in a patient hospitalized in the intensive care unit - Case report.}, journal = {Heliyon}, volume = {11}, number = {4}, pages = {e42793}, pmid = {40084003}, issn = {2405-8440}, abstract = {Clostridioides difficile infections are difficult and serious problem occurring in patients staying in intensive care units. In recent years, the number and severity of these infections, as well as the mortality rate, have been increasing, posing a serious epidemiological problem. This is caused, among other factors, by stressors, artificial nutrition, and sepsis, which lead to disturbances in the patients' microbiome. Basic method of treatment is antibiotic therapy, however some patients experience recurrences of the infection. Fecal Microbiota Transplantation (FMT) is one of the alternative methods used in treating recurring infections of Clostridioides difficile etiology (Clostridioides Difficile Infection, CDI). The presented case refers to a patient with severe pseudomembranous enterocolitis who underwent FMT twice. This report highlights the role of FMT in the treatment of severe Clostridioides difficile infections in critically ill patients.}, }
@article {pmid40083791, year = {2025}, author = {, }, title = {Erratum: Integrative analysis of intestinal flora and untargeted metabolomics in attention-deficit/hyperactivity disorder.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1576969}, doi = {10.3389/fmicb.2025.1576969}, pmid = {40083791}, issn = {1664-302X}, abstract = {[This corrects the article DOI: 10.3389/fmicb.2025.1452423.].}, }
@article {pmid40083245, year = {2025}, author = {Özdirik, B and Berger, H and Tonetti, FR and Cabré, N and Treichel, N and Clavel, T and Tacke, F and Sigal, M and Schnabl, B}, title = {Faecal Cytolysin is Associated With Worse Survival in Patients With Primary Sclerosing Cholangitis.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {45}, number = {4}, pages = {e16181}, doi = {10.1111/liv.16181}, pmid = {40083245}, issn = {1478-3231}, support = {OE821/1-1;Ta434/8-1;CRC1382Project-ID403224013//Deutsche Forschungsgemeinschaft/ ; R01AA24726;R37AA020703;U01AA026939;P30DK120515//National Institutes of Healthy (NIH)/ ; BX004594//Biomedical Laboratory Research &amp; Development Service of the VA Office of Research and Development/ ; }, mesh = {Humans ; *Cholangitis, Sclerosing/mortality/microbiology ; *Feces/microbiology/chemistry ; Male ; Female ; Adult ; Middle Aged ; *Perforin/genetics/metabolism ; *RNA, Ribosomal, 16S/genetics ; Case-Control Studies ; Enterococcus faecalis/isolation &amp; purification ; Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/microbiology/mortality ; Aged ; Liver Transplantation ; Virulence Factors/genetics ; }, abstract = {BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy without treatment options beyond liver transplantation. The gut-liver axis, especially the role of gut microbes, has emerged as a crucial pathway contributing to PSC pathogenesis. Recent research has revealed Enterococcus (E.) faecalis and its virulence factor cytolysin to increase mortality risk in patients with alcohol-associated hepatitis. Thus, we studied the role of enterococci, particularly E. faecalis and its virulence factor genes cytolysin and gelatinase, in faecal samples from patients with PSC.<br><br>METHODS: To assess the relevance of Enterococcus species, we performed 16S rRNA gene amplicon analysis in faecal samples from 60 patients with PSC. We validated our findings by qPCR of faecal microbial DNA in an extended cohort of 105 patients with PSC, 104 patients with inflammatory bowel disease (IBD) and 68 healthy subjects.<br><br>RESULTS: High-throughput 16S rRNA amplicon analysis revealed an increased relative abundance of enterococci in PSC patients compared with healthy controls and IBD patients, respectively, (p&#x2009;<&#x2009;0.0001). PSC patients with high enterococci abundance had a decreased probability of transplant-free survival (p&#x2009;=&#x2009;0.028). E. faecalis and its virulence factors cytolysin and gelatinase were more abundant in patients with PSC. Higher faecal cytolysin was associated with lower overall survival (p&#x2009;=&#x2009;0.04), while survival was independent of gelatinase levels.<br><br>CONCLUSION: Our data highlight the association of E. faecalis and faecal cytolysin with lower survival in patients with PSC. These data should prompt further research into the pathogenic role of cytolysin-positive E. faecalis, and to explore its role as a potential therapeutic target.}, }
@article {pmid40082770, year = {2025}, author = {Jahn, B and Bundo, M and Arvandi, M and Schaffner, M and Todorovic, J and Sroczynski, G and Knudsen, A and Fischer, T and Schiller-Fruehwirth, I and Öfner, D and Renner, F and Jonas, M and Kuchin, I and Kruse, J and Santamaria, J and Ferlitsch, M and Siebert, U}, title = {One in three adenomas could be missed by white-light colonoscopy - findings from a systematic review and meta-analysis.}, journal = {BMC gastroenterology}, volume = {25}, number = {1}, pages = {170}, pmid = {40082770}, issn = {1471-230X}, mesh = {Humans ; *Colonoscopy/methods ; *Adenoma/diagnostic imaging/diagnosis/pathology ; *Colorectal Neoplasms/diagnosis/pathology/diagnostic imaging ; Early Detection of Cancer/methods ; Missed Diagnosis/statistics &amp; numerical data ; Diagnostic Errors/statistics &amp; numerical data ; Light ; }, abstract = {BACKGROUND: White light (conventional) colonoscopy (WLC) is widely used for colorectal cancer screening, diagnosis and surveillance but endoscopists may fail to detect adenomas. Our goal was to assess and synthesize overall and subgroup-specific adenoma miss rates (AMR) of WLC in daily practice.<br><br>METHODS: We conducted a systematic review in MEDLINE, EMBASE, Cochrane Library, and grey literature on studies evaluating diagnostic WLC accuracy in tandem studies with novel-colonoscopic technologies (NCT) in subjects undergoing screening, diagnostic or surveillance colonoscopy. Information on study design, AMR overall and specific for adenoma size, histology, location, morphology and further outcomes were extracted and reported in standardized evidence tables. Study quality was assessed using the QUADAS-2 tool. Random-effects meta-analyses and meta-regression were performed to estimate pooled estimates for AMR with 95% confidence intervals (95% CI) and to explain heterogeneity.<br><br>RESULTS: Out of 5,963 identified studies, we included sixteen studies with 4,101 individuals in our meta-analysis. One in three adenomas (34%; 95% CI: 30-38%) was missed by WLC in daily practice individuals. Subgroup analyses showed significant AMR differences by size (36%, adenomas 1-5&#xa0;mm; 27%, adenomas 6-9&#xa0;mm; 12%, adenomas&#x2009;&#x2265;&#x2009;10&#xa0;mm), histology (non-advanced: 42%, advanced: 21%), morphology (flat: 50%, polypoid: 27%), but not by location (distal: 36%, proximal: 36%).<br><br>CONCLUSIONS: Based on our meta-analysis, one in three adenomas could be missed by WLC. This may significantly contribute to interval cancers. Our results should be considered in health technology assessment when interpreting sensitivity of fecal occult blood or other screening tests derived from studies using WLC as "gold standard".}, }
@article {pmid40082445, year = {2025}, author = {Manns, MP and Bergquist, A and Karlsen, TH and Levy, C and Muir, AJ and Ponsioen, C and Trauner, M and Wong, G and Younossi, ZM}, title = {Primary sclerosing cholangitis.}, journal = {Nature reviews. Disease primers}, volume = {11}, number = {1}, pages = {17}, pmid = {40082445}, issn = {2056-676X}, mesh = {Humans ; *Cholangitis, Sclerosing/physiopathology/therapy/epidemiology/diagnosis/complications ; Liver Transplantation/methods ; Ursodeoxycholic Acid/therapeutic use ; }, abstract = {Primary sclerosing cholangitis (PSC) is a chronic biliary inflammation associated with periductular fibrosis of the intrahepatic and extrahepatic bile ducts leading to strictures, bacterial cholangitis, decompensated liver disease and need for liver transplantation. This rare focal liver disease affects all races and ages, with a predominance of young males. There is an up to 88% association with inflammatory bowel disease. Although the aetiology is unknown and the pathophysiology is poorly understood, PSC is regarded as an autoimmune liver disease based on a strong immunogenetic background. Further, the associated risk for various malignancies, particularly cholangiocellular carcinoma, is also poorly understood. No medical therapy has been approved so far nor has been shown to improve transplant-free survival. However, ursodeoxycholic acid is widely used since it improves the biochemical parameters of cholestasis and is safe at low doses. MRI of the biliary tract is the primary imaging technology for diagnosis. Endoscopic interventions of the bile ducts should be limited to clinically relevant strictures for balloon dilatation, biopsy and brush cytology. End-stage liver disease with decompensation is an indication for liver transplantation with recurrent PSC in up to 38% of patients. Several novel therapeutic strategies are in various stages of development, including apical sodium-dependent bile acid transporter and ileal bile acid transporter inhibitors, integrin inhibitors, peroxisome proliferator-activated receptor agonists, CCL24 blockers, recombinant FGF19, CCR2/CCR5 inhibitors, farnesoid X receptor bile acid receptor agonists, and nor-ursodeoxycholic acid. Manipulation of the gut microbiome includes faecal microbiota transplantation. This article summarizes present knowledge and defines unmet medical needs to improve quality of life and survival.}, }
@article {pmid40081233, year = {2025}, author = {Yang, S and Pan, H and Wang, T and Zhou, X and Fan, L and Xiao, H and Zhou, Z and Xiao, Y and Shi, D}, title = {Bacillus paralicheniformis-mediated gut microbiota promotes M2 macrophage polarization by inhibiting P38 MAPK signaling to alleviate necrotizing enterocolitis and apoptosis in mice.}, journal = {Microbiological research}, volume = {296}, number = {}, pages = {128136}, doi = {10.1016/j.micres.2025.128136}, pmid = {40081233}, issn = {1618-0623}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Enterocolitis, Necrotizing/microbiology/therapy ; *Apoptosis ; *Bacillus/physiology ; *p38 Mitogen-Activated Protein Kinases/metabolism ; Probiotics ; Fecal Microbiota Transplantation ; *Macrophages/immunology/metabolism ; Disease Models, Animal ; Dysbiosis/microbiology/therapy ; Clostridium perfringens ; Clostridium Infections/microbiology/therapy ; Mice, Inbred C57BL ; Male ; MAP Kinase Signaling System ; Signal Transduction ; Indoleacetic Acids/metabolism ; }, abstract = {Clostridial necrotizing enterocolitis is a severe gastrointestinal disease induced by Clostridium, strongly associated with intestinal dysbiosis. Fecal microbiota transplantation (FMT) has proven effective in treating gastrointestinal diseases by remodeling intestinal microbial homeostasis. However, it remains unclear whether FMT from donors with beneficial microbiota can improve the recipient's intestinal function more efficiently. This study found that probiotic Bacillus paralicheniformis SN-6-mediated gut microbiota effectively prevent Clostridial necrotizing enteritis and explored the underlying molecular mechanisms. Data demonstrated that SN-6 altered gut microbiota composition, ameliorated Clostridium perfringens-induced intestinal microbiota dysbiosis and metabolic reprogramming, particularly enhancing tryptophan metabolism. This led to a marked reduction in intestinal barrier damage and inflammation. FMT from SN-6-treated mice reduced jejunal inflammation in Clostridium perfringens-infected mice, strengthened jejunal barrier and enriched beneficial bacteria, such as Lactobacillus, Blautia, Akkermansia. Furthermore, 3-indoleacetic acid (IAA), a metabolite enriched by SN-6, activated aryl hydrocarbon receptor (AhR), suppressed the P38 mitogen-activated protein kinase (P38 MAPK) signaling, and drove macrophage polarization from M0 to M2-type, thereby reducing apoptosis and excessive inflammation. This study highlights Bacillus paralicheniformis SN-6 as a key modulator of intestinal immunomodulation via the gut microbiota-IAA-AhR-P38 MAPK axis, offering a potential therapeutic target for preventing and controlling clostridial necrotizing enteritis.}, }
@article {pmid40079755, year = {2025}, author = {Menozzi, E and Schapira, AHV and Borghammer, P}, title = {The Gut-Brain Axis in Parkinson disease: Emerging Concepts and Therapeutic Implications.}, journal = {Movement disorders clinical practice}, volume = {}, number = {}, pages = {}, doi = {10.1002/mdc3.70029}, pmid = {40079755}, issn = {2330-1619}, support = {ASAP-000420//Aligning Science Across Parkinson's/ ; MR/T046007/1//EU Joint Programme - Neurodegenerative Disease Research/ ; }, abstract = {BACKGROUND: The gut-brain axis, i.e. the bidirectional communication system between the gut and the brain, has become of central importance in Parkinson disease (PD) research over the past 20 years.<br><br>AIMS: We aimed to describe the milestones of the gut-brain axis research in PD and the development of theories proposing the involvement of the gastrointestinal tract in PD pathogenesis.<br><br>METHODS: We searched PubMed using the terms 'gut-brain axis' AND 'Parkinson disease', and selected relevant articles to provide the foundation for reconstructing an historical overview of the gut-brain axis research in PD.<br><br>RESULTS: Mounting evidence from preclinical, clinical and post-mortem studies suggests that a subgroup of PD patients present with a range of prodromal symptoms (e.g., autonomic dysfunction, rapid eye movement sleep behaviour disorder) which reflect initial accumulation and later spread of pathological &#x3b1;-synuclein rostrally from the gastrointestinal tract ("body-first" PD). Through neural connections along the gut-brain axis, pathological &#x3b1;-synuclein may spread to the brain, producing clinically manifest disease. Recently, two mechanisms involving the gut-brain axis have attracted increasing attention for their role in PD pathogenesis and progression, namely the perturbation of the composition of the microorganisms living in the gut (the gut microbiome), and the dysfunction of enteroendocrine cells.<br><br>CONCLUSION: Treatments targeting the gut-brain axis, especially the gut microbiome and the enteroendocrine cells pathway, could potentially slow disease progression or even prevent disease onset. Among these, pre/probiotics, faecal microbiota transplantation, and glucagon-like peptide-1 receptor agonists, have entered advanced stages of clinical trials in humans and shown potential symptomatic and disease-modifying effects.}, }
@article {pmid40078367, year = {2025}, author = {Ullah, H and Arbab, S and Chang, C and Bibi, S and Muhammad, N and Rehman, SU and Suleman,  and Ullah, I and Hassan, IU and Tian, Y and Li, K}, title = {Gut microbiota therapy in gastrointestinal diseases.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1514636}, pmid = {40078367}, issn = {2296-634X}, abstract = {The human gut microbiota, consisting of trillions of microorganisms, plays a crucial role in gastrointestinal (GI) health and disease. Dysbiosis, an imbalance in microbial composition, has been linked to a range of GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and colorectal cancer. These conditions are influenced by the interactions between the gut microbiota, the host immune system, and the gut-brain axis. Recent research has highlighted the potential for microbiome-based therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary modifications, to restore microbial balance and alleviate disease symptoms. This review examines the role of gut microbiota in the pathogenesis of common gastrointestinal diseases and explores emerging therapeutic approaches aimed at modulating the microbiome. We discuss the scientific foundations of these interventions, their clinical effectiveness, and the challenges in their implementation. The review underscores the therapeutic potential of microbiome-targeted treatments as a novel approach to managing GI disorders, offering personalized and alternative options to conventional therapies. As research in this field continues to evolve, microbiome-based interventions hold promise for improving the treatment and prevention of gastrointestinal diseases.}, }
@article {pmid40077957, year = {2025}, author = {Ma, Z and Wen, X and Zhang, Y and Ai, Z and Zhao, X and Dong, N and Dou, X and Shan, A}, title = {Thymol Alleviates Colitis by Modulating Intestinal Barrier Damage, Gut Microbiota, and Amino Acid Metabolic Pathways.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {12}, pages = {7211-7227}, doi = {10.1021/acs.jafc.4c10406}, pmid = {40077957}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Colitis/chemically induced/metabolism/drug therapy/microbiology ; *Amino Acids/metabolism ; Humans ; *Mice, Inbred C57BL ; *Intestinal Mucosa/metabolism/drug effects ; *Thymol/pharmacology/administration &amp; dosage/metabolism ; Male ; Bacteria/classification/genetics/metabolism/isolation &amp; purification/drug effects ; Metabolic Networks and Pathways/drug effects ; Dextran Sulfate/adverse effects ; Colon/metabolism/microbiology/drug effects ; Cytokines/metabolism/genetics ; }, abstract = {Thymol (THY) is a phenolic monoterpene compound that has garnered attention due to its various biological properties, including antioxidant, anti-inflammatory, and immune-regulatory effects. The purpose of this study was to determine the therapeutic and protective effects of THY in colitic mice, with a particular focus on the mechanisms involving gut microbiota. The results showed that early intervention with THY (40 and 80 mg/kg) not only alleviated the clinical symptoms and colonic damage in mice with dextran sodium sulfate (DSS)-induced colitis but also suppressed the colonic production of inflammatory cytokines (IL-1β, IL-6, and IL-18) and enhanced the expression of mucins (MUC1 and MUC2) and trefoil factor family 3 (TFF3), thereby improving the integrity of the intestinal epithelial barrier. In addition, THY altered the composition of the gut microbiota in colitis mice by increasing the abundance of Bacteroides and reducing the abundance of Proteobacteria. Fecal microbial transplantation (FMT) results demonstrated that FM from THY donor mice significantly improved symptoms of inflammatory bowel disease (IBD), confirming the crucial role of the gut microbiota. Metagenomic and untargeted metabolomic studies found that the characteristic microbiota of THY is Prevotellaceae, and THY significantly upregulated the amino acid metabolic pathways related to arginine and proline metabolism, arginine biosynthesis, and glycerophospholipid metabolism. In summary, THY holds significant potential as a functional additive to enhance host intestinal activity.}, }
@article {pmid40077671, year = {2025}, author = {Gao, Y and Borjihan, Q and Zhang, W and Li, L and Wang, D and Bai, L and Zhu, S and Chen, Y}, title = {Complex Probiotics Ameliorate Fecal Microbiota Transplantation-Induced IBS in Mice via Gut Microbiota and Metabolite Modulation.}, journal = {Nutrients}, volume = {17}, number = {5}, pages = {}, pmid = {40077671}, issn = {2072-6643}, support = {2022-Science and Technology Xing Meng-Quality improvement-02//the Science and Technology Xing Meng action focus project of Inner Mongolia Autonomous Region/ ; 2022-Science and Technology Xing Meng-Quality improvement-02//the Science and Technology Xing Meng action focus project of Inner Mongolia Autonomous Region/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Irritable Bowel Syndrome/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Probiotics/pharmacology ; Mice ; *Feces/microbiology ; *Disease Models, Animal ; Mice, Inbred C57BL ; Male ; Dysbiosis/therapy ; Serotonin/metabolism ; Serotonin Plasma Membrane Transport Proteins/metabolism ; Acetic Acid ; Constipation/therapy/microbiology/metabolism ; Butyric Acid/metabolism ; Tryptophan/metabolism ; }, abstract = {Background/Objectives: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Emerging evidence implicates gut microbiota dysbiosis in IBS pathogenesis, and probiotic interventions targeting microbial modulation hold therapeutic promise. Methods: this study used fecal microbiota transplantation to establish a mouse model of IBS before evaluating the effects of the complex probiotic by using metagenomics and targeted metabolomics to explore the potential mechanism. Results: After 14 days, the probiotic relieved constipation, reduced inflammation and intestinal permeability, lowered 5-HT levels and increased serotonin transporter (SERT) expression in tissues. Metagenomic analysis showed a reduced inflammation-related species abundance. It also decreased fecal butyric acid, acetic acid and tryptophan levels in IBS mice. Conclusions: The probiotic complex effectively alleviated IBS symptoms in mice by modulating gut microbiota and fecal metabolites, providing insights for future IBS research and treatment.}, }
@article {pmid40076864, year = {2025}, author = {Hatamnejad, MR and Medzikovic, L and Dehghanitafti, A and Rahman, B and Vadgama, A and Eghbali, M}, title = {Role of Gut Microbial Metabolites in Ischemic and Non-Ischemic Heart Failure.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, pmid = {40076864}, issn = {1422-0067}, support = {R01 HL174472/HL/NHLBI NIH HHS/United States ; R01HL147586/NH/NIH HHS/United States ; R01HL159865/NH/NIH HHS/United States ; 24CDA1263497//American Heart Association/ ; R01 HL162124/HL/NHLBI NIH HHS/United States ; R01HL162124/NH/NIH HHS/United States ; R01 HL147586/HL/NHLBI NIH HHS/United States ; R01 HL159865/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Heart Failure/metabolism ; Animals ; Hydrogen Sulfide/metabolism ; Fatty Acids, Volatile/metabolism ; Myocardial Ischemia/metabolism/microbiology ; Methylamines/metabolism ; }, abstract = {The effect of the gut microbiota extends beyond their habitant place from the gastrointestinal tract to distant organs, including the cardiovascular system. Research interest in the relationship between the heart and the gut microbiota has recently been emerging. The gut microbiota secretes metabolites, including Trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids (BAs), indole propionic acid (IPA), hydrogen sulfide (H2S), and phenylacetylglutamine (PAGln). In this review, we explore the accumulating evidence on the role of these secreted microbiota metabolites in the pathophysiology of ischemic and non-ischemic heart failure (HF) by summarizing current knowledge from clinical studies and experimental models. Elevated TMAO contributes to non-ischemic HF through TGF-ß/Smad signaling-mediated myocardial hypertrophy and fibrosis, impairments of mitochondrial energy production, DNA methylation pattern change, and intracellular calcium transport. Also, high-level TMAO can promote ischemic HF via inflammation, histone methylation-mediated vascular fibrosis, platelet hyperactivity, and thrombosis, as well as cholesterol accumulation and the activation of MAPK signaling. Reduced SCFAs upregulate Egr-1 protein, T-cell myocardial infiltration, and HDAC 5 and 6 activities, leading to non-ischemic HF, while reactive oxygen species production and the hyperactivation of caveolin-ACE axis result in ischemic HF. An altered BAs level worsens contractility, opens mitochondrial permeability transition pores inducing apoptosis, and enhances cholesterol accumulation, eventually exacerbating ischemic and non-ischemic HF. IPA, through the inhibition of nicotinamide N-methyl transferase expression and increased nicotinamide, NAD+/NADH, and SIRT3 levels, can ameliorate non-ischemic HF; meanwhile, H2S by suppressing Nox4 expression and mitochondrial ROS production by stimulating the PI3K/AKT pathway can also protect against non-ischemic HF. Furthermore, PAGln can affect sarcomere shortening ability and myocyte contraction. This emerging field of research opens new avenues for HF therapies by restoring gut microbiota through dietary interventions, prebiotics, probiotics, or fecal microbiota transplantation and as such normalizing circulating levels of TMAO, SCFA, BAs, IPA, H2S, and PAGln.}, }
@article {pmid40076603, year = {2025}, author = {Wang, K and Hu, Y and Wu, Y and Xu, J and Zhao, Y and Yang, J and Li, X}, title = {The Therapeutic Potential of Gut-Microbiota-Derived Metabolite 4-Phenylbutyric Acid in Escherichia coli-Induced Colitis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, pmid = {40076603}, issn = {1422-0067}, support = {32360904//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis/microbiology/drug therapy/metabolism/chemically induced ; Mice ; *Escherichia coli ; *Phenylbutyrates/pharmacology/therapeutic use ; *Escherichia coli Infections/microbiology/drug therapy ; *Fecal Microbiota Transplantation ; *Toll-Like Receptor 4/metabolism ; *Myeloid Differentiation Factor 88/metabolism/genetics ; Disease Models, Animal ; Cytokines/metabolism ; NF-kappa B/metabolism ; Cattle ; Signal Transduction/drug effects ; Female ; }, abstract = {Pathogenic Escherichia coli (E. coli) is a widely distributed pathogen that can cause varying degrees of zoonotic diseases, and infected animals often experience intestinal inflammation accompanied by diarrhea and dysbiosis. Previously, for the first time, we isolated Escherichia coli primarily of type B2 from a large-scale dairy farm in Yunnan, China. The 16s rRNA sequencing showed significant differences in the gut microbiota of calves infected with B2 E. coli, with higher abundance of harmful bacteria and lower abundance of beneficial bacteria compared with healthy calves. The metabolomics indicated that the concentrations of oxoadipic acid, 16-oxopalmitate, oerillyl alcohol, palmitoleic acid, and 4-phenylbutyrate (4-PBA) were significantly higher in the healthy group than in the infected group. The mouse model was established to assess the regulatory effect of 4-PBA on E. coli-induced colitis. Both oral administration of 4-PBA and fecal microbiota transplantation (FMT) had strong resistance to E. coli infection, improved survival rate and body weight, reduced intestinal tissue damage, decreased the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and restrained TLR4/MyD88/NF-κB pathway. Our study demonstrated that 4-PBA could relieve E. coli-induced colitis by improving gut microbiota structure and inhibiting the expression of pro-inflammatory cytokines through the TLR4/MyD88/NF-κB pathway. The present finding reveals the therapeutic potential of the gut-microbiota-derived metabolite 4-PBA for the treatment of colitis caused by E. coli.}, }
@article {pmid40075967, year = {2025}, author = {Luo, S and Huang, X and Chen, S and Li, J and Wu, H and He, Y and Zhou, L and Liu, B and Feng, J}, title = {The Gut Microbiota of the Greater Horseshoe Bat Confers Rapidly Corresponding Immune Cells in Mice.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {5}, pages = {}, pmid = {40075967}, issn = {2076-2615}, support = {202311439011//College Students' Innovative Entrepreneurial Training Plan Program/ ; }, abstract = {BACKGROUND: Emerging infectious diseases threaten human and animal health, with most pathogens originating from wildlife. Bats are natural hosts for many infectious agents. Previous studies have demonstrated that changes in some specific genes in bats may contribute to resistance to viral infections, but they have mostly overlooked the immune function of the bat gut microbiota.<br><br>AIMS: In this study, we used fecal transplants to transfer the gut microbiota from the Greater Horseshoe Bat (Rhinolophus ferrumequinum) into mice treated with antibiotics. The gut microbiota changes in mice were detected using 16S rRNA high-throughput sequencing technology. Flow cytometry was used to detect changes in associated immune cells in the spleen and mesenteric lymph nodes of the mice.<br><br>RESULTS: The results showed that the gut microbiota of mice showed characteristics of some bat gut microbiota. The Greater Horseshoe Bat's gut microbiota changed some immune cells' composition in the spleen and mesenteric lymph nodes of mice and also conferred a faster and higher proportion of natural killer cell activation.<br><br>CONCLUSION: This result provides new evidence for the regulatory immune function of bat gut microbiota and contributes to a deeper insight into the unique immune system of bats.}, }
@article {pmid40075266, year = {2025}, author = {Cao, H and Xu, J and Wang, H and Yi, W and Yang, D and Yang, J and Sun, J and Wang, Y and Zhang, F and Yan, J and Li, D}, title = {Fecal microbiota transplantation mitigates postdieting weight regain in mice by modulating the gut-liver axis.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {135}, pmid = {40075266}, issn = {1471-2180}, support = {2023YFF1104305//National Key Research and Development Program of China/ ; 2022YFF1100601//National Key Research and Development Program of China/ ; K2023004//Key Research project of Health Commission of Jiangsu Province/ ; M2021055//Key Research project of Health Commission of Jiangsu Province/ ; Y2021001//Wuxi Science and Technology Bureau, "Taihu Light" Science and Technology Research program/ ; K20221026//Wuxi Science and Technology Bureau, "Taihu Light" Science and Technology Research program/ ; CXTD2021003//Key discipline construction program of Wuxi Commission of Health/ ; KX-23-B050//Soft Science Project of Wuxi Science and Technology Association/ ; KX-23-C196//Soft Science Project of Wuxi Science and Technology Association/ ; YJZ202305//Medical research projects in research-oriented hospitals of Affiliated Hospital of Jiangnan University/ ; HB2023062//"Shuangbai Talents" research program of Wuxi Commission of Health/ ; HB2023063//"Shuangbai Talents" research program of Wuxi Commission of Health/ ; HB2023061//"Shuangbai Talents" research program of Wuxi Commission of Health/ ; LCYJ202347//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; LCYJ202310//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; LCYJ202322//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; LCYJ202303//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; BK20210468//Natural Science Foundation of Jiangsu Province/ ; BK20210060//Natural Science Foundation of Jiangsu Province/ ; 82370809//National Natural Science Foundation of China/ ; 32101033//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Mice ; *Weight Gain ; *Liver/metabolism ; Male ; Bacteria/classification/isolation &amp; purification/genetics/metabolism ; Mice, Inbred C57BL ; Feces/microbiology ; Dysbiosis/therapy/microbiology ; Fatty Acids, Volatile/metabolism ; Lipid Metabolism ; }, abstract = {BACKGROUND: Dysbiosis of the microbiome is strongly associated with weight rebound after dieting. However, the interactions between the host and microbiome and their relevance to the pathogenesis of post-diet weight rebound remain unclear.<br><br>PURPOSE: This study aimed to evaluate the effects of fecal microbiota transplantation (FMT) on post-diet weight regain and to investigate the underlying mechanisms by which FMT inhibits weight regain.<br><br>METHODS: FMT was administered once daily to mice for 5 weeks. Gas chromatography tandem mass spectrometry was employed to analyze short-chain fatty acid levels in serum, ultrahigh-performance liquid chromatography tandem mass spectrometry was utilized for analyzing hepatic lipid metabolites, and shotgun metagenomic sequencing was applied to examine the intestinal microbiome.<br><br>RESULTS: FMT reduced weight regain and prevented lipid accumulation in both liver and adipose tissue while also improving glucose intolerance in mice. Furthermore, FMT increased the abundance of Enterorhabdus caecimuris and decreased the abundances of Burkholderiales, Sutterellaceae, Turicimonas muris, Bacteroides stercorirosoris, and Acetivibrio ethanolgignens within the gut microbiota. Additionally, elevated propionic acid levels and significant alterations in hepatic lipid metabolites were observed following FMT administration.<br><br>CONCLUSIONS: Our findings demonstrate that FMT effectively mitigates post-diet weight regain and associated complications. These effects are mediated through interactions between the gut microbiota and the liver via the gut-propionic acid-liver axis.<br><br>CLINICAL TRIAL NUMBER: Not applicable.}, }
@article {pmid40074992, year = {2025}, author = {Bakhshandi, AK and Minasazi, A and Yeganeh, O and Behi, M}, title = {Therapeutic potential of microbiota modulation in psoriasis: current evidence and future directions.}, journal = {Archives of dermatological research}, volume = {317}, number = {1}, pages = {561}, pmid = {40074992}, issn = {1432-069X}, mesh = {*Psoriasis/immunology/therapy/microbiology ; Humans ; *Probiotics/therapeutic use ; *Dysbiosis/immunology/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; Skin/microbiology/immunology/pathology ; Quality of Life ; }, abstract = {The human microbiota plays a significant role in health and the development of autoimmune diseases by maintaining gut-skin homeostasis through diverse microbial communities. Dysbiosis, or imbalance in these communities, is increasingly recognized as a contributing factor in the pathogenesis of autoimmune and inflammatory diseases, including psoriasis. Psoriasis is characterized by immune dysregulation, leading to red and scaly plaques that significantly reduce patients' quality of life. Current evidence highlights the gut microbiota's critical role in driving immune responses and chronic inflammation associated with psoriasis. Therapeutic strategies aimed at restoring microbial balance, such as probiotics, have demonstrated promise in reducing disease severity. Additionally, fecal microbiota transplantation (FMT) has emerged as a novel intervention, with early studies suggesting its potential to alleviate symptoms by correcting gut dysbiosis. These approaches underscore the importance of microbiota-targeted therapies in addressing the systemic nature of psoriasis and pave the way for advancements in personalized treatment strategies.}, }
@article {pmid40074633, year = {2025}, author = {Le, PH and Yeh, YM and Chen, YC and Chen, CL and Tsou, YK and Chen, CC and Chiu, CT and Chiu, CH}, title = {Fecal microbiota transplantation for vancomycin-resistant Clostridium innocuum infection in inflammatory bowel disease: A pilot study evaluating safety and clinical and microbiota outcome.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jmii.2025.03.004}, pmid = {40074633}, issn = {1995-9133}, abstract = {BACKGROUND: Clostridium innocuum is a vancomycin-resistant pathobiome associated with poor clinical outcomes in inflammatory bowel disease (IBD). In ulcerative colitis (UC), it correlates with reduced remission rates, while in Crohn's disease (CD), it is linked to creeping fat formation and intestinal strictures. Notably, some patients experience refractory or recurrent C. innocuemailum infections despite metronidazole treatment. This study evaluates the safety and efficacy of single-dose fecal microbiota transplantation (FMT) in IBD patients with refractory or recurrent C. innocuum infections.<br><br>METHODS: We conducted a feasibility pilot study involving seven IBD patients (3 CD, 4 UC) with refractory (n&#xa0;=&#xa0;5) or recurrent (n&#xa0;=&#xa0;2) C. innocuum infections following metronidazole treatment. Patients underwent single-dose FMT and were monitored for six months.<br><br>RESULTS: No adverse events were recorded. All participants demonstrated improved disease activity post-FMT, as assessed by the Crohn's Disease Activity Index and Mayo Score. However, a mild increase in symptom severity was noted at six months. Follow-up cultures showed persistent C. innocuum infection in one patient and asymptomatic recurrence in another at three months. Alpha diversity of the gut microbiome increased post-FMT, and Bray-Curtis dissimilarity analysis revealed a microbiota composition more similar to that of the donor.<br><br>CONCLUSION: Single-dose FMT appears to be a safe and feasible therapeutic approach for refractory or recurrent C. innocuum infections in IBD patients, with potential benefits in disease activity and microbiome restoration. Further studies are warranted to optimize long-term outcomes.}, }
@article {pmid40072575, year = {2025}, author = {Habeeb, TAAM and Chiaretti, M and Kryvoruchko, IA and Pesce, A and Kechagias, A and Elias, AA and Adam, AAM and Gadallah, MA and Ali Ahmed, SM and Khyrallh, A and Alsayed, MH and Tharwat Kamel Awad, E and Elshafey, MH and Abo Alsaad, MI and Ali, AK and Elbelkasi, H and Abou Zaid, MA and Youssef, HAA and Al-Zamek, MMF and Fiad, A and Elshahidy, TM and Elballat, MR and El Taher, AK and Mohamed, MMM and AboZeid, AK and Mansour, MI and Yassin, MA and Arafa, AS and Lotfy, M and Mousa, B and Atef, B and Naguib, SM and Heggy, IA and Elnemr, M and Zaitoun, MA and AbdAllah, ES and Moussa, MS and Hamed, AEM and Elsayed, RS}, title = {Mucosal advancement flap versus ligation of the inter-sphincteric fistula tract for management of trans-sphincteric perianal fistulas in the elderly: a retrospective study.}, journal = {International journal of colorectal disease}, volume = {40}, number = {1}, pages = {61}, pmid = {40072575}, issn = {1432-1262}, mesh = {Humans ; Aged ; Retrospective Studies ; Male ; *Rectal Fistula/surgery ; Female ; *Surgical Flaps ; *Anal Canal/surgery/physiopathology ; *Recurrence ; Ligation ; *Fecal Incontinence/etiology ; Middle Aged ; Risk Factors ; Treatment Outcome ; Postoperative Complications/etiology ; Intestinal Mucosa/surgery ; }, abstract = {PURPOSE: There is no consensus on the standard approach for trans-sphincteric perianal fistulas (TPAF) in the elderly population. The most commonly used sphincter-saving procedures are ligation of the inter-sphincteric fistula tract (LIFT) and mucosal advancement flap (MAF). We aimed to evaluate the incidence and risk factors for recurrence and incontinence in elderly patients with TPAF using both approaches.<br><br>METHODS: This retrospective study included 257 patients who underwent LIFT (136 patients) or MAF (121 patients) for de novo and cryptoglandular TPAF between July 2018 and July 2021. Recurrent fistulas were clinically and radiologically detected using MRI. Postoperative incontinence was evaluated using the Wexner score and anorectal manometry. Logistic regression analysis was used to detect the risks of recurrence and incontinence.<br><br>RESULTS: The median ages of the patients were 68 (64, 74) and 68 (65, 74) years in the LIFT and MAF groups, respectively. Higher recurrence rates were observed after LIFT (17 (12.5%)) than after MAF (13 (10.7%)), but the difference was not statistically significant (P&#x2009;=&#x2009;0.662). Postoperative incontinence was observed in 18 patients (13.2%) and seven patients (5.8%) in the LIFT and MAF groups, respectively (P&#x2009;=&#x2009;0.044). The predictors for fistula recurrence were smoking (OR, 75.52; 95% CI, 1.02 to 5611.35; P&#x2009;=&#x2009;0.049), length of tract (OR, 17.3; 95% CI, 1.49 to 201.13; P&#x2009;=&#x2009;0.023), and CD classification (OR, 7.08; 95% CI, 1.51 to 33.14; P&#x2009;=&#x2009;0.013). A low Charlson comorbidity index score (&#x2264;&#x2009;5) (OR, 0.68; 95% CI, 0.47 to 0.99; P&#x2009;=&#x2009;0.046) and high postoperative mean squeeze anal pressure (OR, 0.97; 95% CI, 0.95 to 0.99; P&#x2009;=&#x2009;0.001) were significant factors associated with reduced risk of incontinence. In particular, LIFT was associated with a significantly higher risk of incontinence than MAF (OR, 2.089; 95% CI, 1.006 to 4.33; P&#x2009;=&#x2009;0.04).<br><br>CONCLUSIONS: The healing rates of MAF and LIFT procedures did not differ significantly; however, continence was significantly better after MAF. MAF should be added to the guidelines as a good option for the treatment of TPAF in elderly patients.<br><br>TRIAL REGISTRATION: The study was registered as a clinical trial www.<br><br>CLINICALTRIALS: gov (NCT06616662).}, }
@article {pmid40072345, year = {2025}, author = {Chen, M and Song, Y and Pan, J and Liu, S and Zheng, X}, title = {Effects of faecal microbiota transplantation supplemented with inulin on early immunity and immune organ histomorphology in chickens.}, journal = {British poultry science}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/00071668.2025.2458581}, pmid = {40072345}, issn = {1466-1799}, abstract = {1. Faecal microbiota transplantation (FMT) is a technique that promotes gut microbiota diversity and abundance by transplantation of faeces into a recipient's gastrointestinal tract via multiple routes.2. Inulin, a plant polysaccharide, is a natural functional dietary fibre found in a variety of plants, including vegetables and fruits. Inulin can inhibit pathogenic bacterial growth by lowering pH, promote mineral absorption and improve intestinal barrier integrity.3. In this study 90 one-day-old chicks were randomly into three groups; control (CON) group was fed a basic diet; FMT group fed two diets containing 40 ml faecal microbial suspension; and INU group fed a diet containing 1.5% inulin and 40 ml faecal microbial suspension.4. Administering the FMT mixed with inulin effectively reduced blood levels of IL-1β, IL-4 and IL-6, promoted the growth of thymus, bursa of Fabricius and spleen. In addition, it enhanced intestinal barrier function, increased intestinal goblet cells and Paneth cells production, promoted probiotic colonisation and butyrate formation and reduced intestinal inflammation.5. In summary, inulin mixed with FMT promoted the growth of the bursa of Fabricius, thymus and spleen as well as facilitated early growth of chick by promoting intestinal health, reducing inflammation and boosting chick immunity.}, }
@article {pmid40072088, year = {2025}, author = {Świdnicka-Siergiejko, A and Daniluk, J and Miniewska, K and Daniluk, U and Guzińska-Ustymowicz, K and Pryczynicz, A and Dąbrowska, M and Rusak, M and Ciborowski, M and Dąbrowski, A}, title = {Inflammatory Stimuli and Fecal Microbiota Transplantation Accelerate Pancreatic Carcinogenesis in Transgenic Mice, Accompanied by Changes in the Microbiota Composition.}, journal = {Cells}, volume = {14}, number = {5}, pages = {}, pmid = {40072088}, issn = {2073-4409}, support = {No NCN 2017/27/B/NZ5/02904//National Science Center/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Mice, Transgenic ; *Pancreatic Neoplasms/microbiology/genetics/pathology ; Mice ; *Inflammation/pathology/microbiology ; *Gastrointestinal Microbiome/genetics ; *Carcinoma, Pancreatic Ductal/microbiology/genetics/pathology ; Carcinogenesis/genetics/pathology ; Feces/microbiology ; Proto-Oncogene Proteins p21(ras)/genetics ; Pancreas/pathology ; }, abstract = {An association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described. To better understand the bacterial microbiota changes accompanying PDAC promotion and progression stimulated by inflammation and fecal microbiota transplantation (FMT), we investigated stool and pancreatic microbiota by 16s RNA-based metagenomic analysis in mice with inducible acinar transgenic expressions of KrasG12D, and age- and sex-matched control mice that were exposed to inflammatory stimuli and fecal microbiota obtained from mice with PDAC. Time- and inflammatory-dependent stool and pancreatic bacterial composition alterations and stool alpha microbiota diversity reduction were observed only in mice with a Kras mutation that developed advanced pancreatic changes. Stool Actinobacteriota abundance and pancreatic Actinobacteriota and Bifidobacterium abundances increased. In contrast, stool abundance of Firmicutes, Verrucomicrobiota, Spirochaetota, Desulfobacterota, Butyricicoccus, Roseburia, Lachnospiraceae A2, Lachnospiraceae unclassified, and Oscillospiraceae unclassified decreased, and pancreatic detection of Alloprevotella and Oscillospiraceae uncultured was not observed. Furthermore, FMT accelerated tumorigenesis, gradually decreased the stool alpha diversity, and changed the pancreatic and stool microbial composition in mice with a Kras mutation. Specifically, the abundance of Actinobacteriota, Bifidobacterium and Faecalibaculum increased, while the abundance of genera such as Lachnospiraceace A2 and ASF356, Desulfovibrionaceace uncultured, and Roseburia has decreased. In conclusion, pancreatic carcinogenesis in the presence of an oncogenic Kras mutation stimulated by chronic inflammation and FMT dynamically changes the stool and pancreas microbiota. In particular, a decrease in stool microbiota diversity and abundance of bacteria known to be involved in short-fatty acids production were observed. PDAC mouse model can be used for further research on microbiota-PDAC interactions and towards more personalized and effective cancer therapies.}, }
@article {pmid40071861, year = {2025}, author = {Organski, AC and Rajwa, B and Reddivari, A and Jorgensen, JS and Cross, TL}, title = {Gut microbiome-driven regulation of sex hormone homeostasis: a potential neuroendocrine connection.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2476562}, pmid = {40071861}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Male ; Female ; Mice ; *Homeostasis ; *Fecal Microbiota Transplantation ; Gonadal Steroid Hormones/metabolism/blood ; Mice, Inbred C57BL ; Germ-Free Life ; Bacteria/classification/metabolism/isolation &amp; purification/genetics ; Testosterone/blood/metabolism ; Testis/metabolism/microbiology ; Hypothalamo-Hypophyseal System/metabolism ; Feces/microbiology ; Neurosecretory Systems/metabolism ; }, abstract = {The gut microbiome is known to have a bidirectional relationship with sex hormone homeostasis; however, its role in mediating interactions between the primary regulatory axes of sex hormones and their productions is yet to be fully understood. We utilized both conventionally raised and gnotobiotic mouse models to investigate the regulatory role of the gut microbiome on the hypothalamic-pituitary-gonadal (HPG) axis. Male and female conventionally raised mice underwent surgical modifications as follows: (1) hormonally intact controls; (2) gonadectomized males and females; (3) gonadectomized males and females supplemented with testosterone and estrogen, respectively. Fecal samples from these mice were used to colonize sex-matched, intact, germ-free recipient mice through fecal microbiota transplant (FMT). Serum gonadotropins, gonadal sex hormones, cecal microbiota, and the serum global metabolome were assessed. FMT recipients of gonadectomized-associated microbiota showed lower circulating gonadotropin levels than recipients of intact-associated microbiota, opposite to that of FMT donors. FMT recipients of gonadectomized-associated microbiota also had greater testicular weights compared to recipients of intact-associated microbiota. The gut microbiota composition of recipient mice differed significantly based on the FMT received, with the male microbiota having a more concerted impact in response to changes in the HPG axis. Network analyses showed that multiple metabolically unrelated pathways may be involved in driving differences in serum metabolites due to sex and microbiome received in the recipient mice. In sum, our findings indicate that the gut microbiome responds to the HPG axis and subsequently modulates its feedback mechanisms. A deeper understanding of interactions between the gut microbiota and the neuroendocrine-gonadal system may contribute to the development of therapies for sexually dimorphic diseases.}, }
@article {pmid40070843, year = {2025}, author = {Ren, S and Zhang, Y and Wang, X and Su, J and Wang, X and Yuan, Z and He, X and Guo, S and Chen, Y and Deng, S and Wu, X and Li, M and Du, F and Zhao, Y and Shen, J and Hu, W and Li, X and Xiao, Z}, title = {Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1526967}, pmid = {40070843}, issn = {1664-3224}, mesh = {Humans ; *Carcinoma, Hepatocellular/immunology/therapy/microbiology ; *Liver Neoplasms/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Tumor Microenvironment/immunology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progression, particularly its effects on immune cells within the HCC tumor microenvironment (TME). Furthermore, we explore the potential of gut microbiota-targeted interventions, such as antibiotics, probiotics, prebiotics, and fecal microbiota transplantation (FMT), to modulate the immune response and improve outcomes of immunotherapy in HCC. By synthesizing insights from recent studies, this review aims to highlight microbiota-based strategies that may enhance immunotherapy outcomes, advancing personalized approaches in HCC treatment.}, }
@article {pmid40068791, year = {2025}, author = {Huang, H and Zhao, T and Ma, W}, title = {Omega-3 polyunsaturated fatty acids attenuates cognitive impairment via the gut-brain axis in diabetes-associated cognitive dysfunction rats.}, journal = {Brain, behavior, and immunity}, volume = {127}, number = {}, pages = {147-169}, doi = {10.1016/j.bbi.2025.03.015}, pmid = {40068791}, issn = {1090-2139}, abstract = {Diabetes-related cognitive dysfunction (DACD) is a comorbidity of type 2 diabetes that has a negative effect on patients' quality of life. Research has indicated that disruption of the gut microbiota (GM) may be linked to dementia with altered cognitive performance. Conversely, omega-3 polyunsaturated fatty acids (n-3 PUFAs) may reverse DACD. The present study aimed to assess the effects of an n-3 PUFA intervention and fecal microbiota transplantation (FMT) on high-fat and streptozotocin-induced DACD model rats. In DACD rats, n-3 PUFA treatment restored fasting blood glucose (FBG) levels and cognitive function, increased the expression of anti-inflammatory cytokines and downregulated the expression of proinflammatory cytokines in the cortex and colon. Additionally, the expression of the postsynaptic density protein-95 mRNA and protein varied with n-3 PUFA treatment. Treatment with n-3 PUFAs also increased the expression of tight junction proteins. Beneficial and short-chain fatty acid-producing bacteria were more abundant when rats were exposed to n-3 PUFAs. After FMT from the rats with DACD symptoms that were improved by the n-3 PUFA dietary intervention into another batch of DACD rats, we observed recovery in recipient DACD rats. These results indicated that the alleviation of DACD symptoms by n-3 PUFAs was attributed to gut microbiota remodeling.}, }
@article {pmid40066068, year = {2025}, author = {Ganesan, R and Thirumurugan, D and Vinayagam, S and Kim, DJ and Suk, KT and Iyer, M and Yadav, MK and HariKrishnaReddy, D and Parkash, J and Wander, A and Vellingiri, B}, title = {A critical review of microbiome-derived metabolic functions and translational research in liver diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1488874}, pmid = {40066068}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Diseases/microbiology/metabolism ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; Animals ; *Translational Research, Biomedical ; *Probiotics/therapeutic use ; Liver/metabolism/microbiology ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Significant changes in gut microbial composition are associated with chronic liver disease. Using preclinical models, it has been demonstrated that ethanol/alcohol-induced liver disease is transmissible through fecal microbiota transplantation (FMT). So, the survival rate of people with severe alcoholic hepatitis got better, which suggests that changes in the makeup and function of gut microbiota play a role in metabolic liver disease. The leaky intestinal barrier plays a major role in influencing metabolic-related liver disease development through the gut microbiota. As a result, viable bacteria and microbial products can be transported to the liver, causing inflammation, contributing to hepatocyte death, and causing the fibrotic response. As metabolic-related liver disease starts and gets worse, gut dysbiosis is linked to changes in the immune system, the bile acid composition, and the metabolic function of the microbiota in the gut. Metabolic-related liver disease, as well as its self-perpetuation, will be demonstrated using data from preclinical and human studies. Further, we summarize how untargeted treatment approaches affect the gut microbiota in metabolic-related liver disease, including dietary changes, probiotics, antibiotics, and FMT. It discusses how targeted therapies can improve liver disease in various areas. These approaches may improve metabolic-related liver disease treatment options.}, }
@article {pmid40064933, year = {2025}, author = {Madill-Thomsen, KS and Venner, JM and Parsons, DE and Famulski, KS and Thiesen, AL and Hoque, S and Kroeker, KI and Wong, K and Peerani, F and Dieleman, LA and Hoentjen, F and Baumgart, DC and Halloran, PF and Halloran, BP}, title = {Relating the molecular phenotype of ulcerative colitis to the clinical course.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {8342}, pmid = {40064933}, issn = {2045-2322}, mesh = {Humans ; *Colitis, Ulcerative/genetics/metabolism/pathology ; Male ; Female ; Adult ; Middle Aged ; *Leukocyte L1 Antigen Complex/metabolism ; Prospective Studies ; Phenotype ; Disease Progression ; Biopsy ; Aged ; Immunity, Innate ; Colon/pathology/metabolism ; }, abstract = {The expanding portfolio of targeted therapies for ulcerative colitis (UC) suggests that a more precise approach to defining disease activity will aid clinical decision-making. This prospective study used genome-wide microarrays to characterize gene expression in biopsies from the most inflamed colon segments from patients with UC and analyzed associations between molecular changes and short-term outcomes while on standard-of-care treatment. We analyzed 141 biopsies-128 biopsies from 112 UC patients and 13 biopsies from eight inflammatory bowel disease unclassified (IBDU) patients. Endoscopic disease was associated with expression of innate immunity transcripts, e.g. complement factor B (CFB); inflammasome genes (ZBP1 and PIM2); calprotectin (S100A8 and S100A9); and inflammation-, injury-, and innate immunity-associated pathway analysis terms. A cross-validated molecular machine learning classifier trained on the endoscopic Mayo subscore predicted the endoscopic Mayo subscore with area-under-the-curve of 0.85. A molecular calprotectin transcript score showed strong associations with fecal calprotectin and the endoscopic Mayo subscore. Logistic regression models showed that molecular features (e.g. molecular classifier and molecular calprotectin scores) improved the prediction of disease progression over conventional, clinical features alone (e.g. total Mayo score, fecal calprotectin, physician global assessment). The molecular features of UC showed strong correlations with disease activity and permitted development of machine-learning predictive disease classifiers that can be applied to expanded testing in diverse cohorts.}, }
@article {pmid40063530, year = {2025}, author = {Serbanescu, M and Lee, S and Li, F and Boppana, SH and Elebasy, M and White, JR and Mintz, CD}, title = {Effects of Perioperative Exposure on the Microbiome and Outcomes From an Immune Challenge in C57Bl/6 Adult Mice.}, journal = {Anesthesia and analgesia}, volume = {}, number = {}, pages = {}, doi = {10.1213/ANE.0000000000007467}, pmid = {40063530}, issn = {1526-7598}, abstract = {BACKGROUND: Previous work suggests that the gut microbiome can be disrupted by antibiotics, anesthetics, opiates, supplemental oxygen, or nutritional deprivation-all of which are common and potentially modifiable perioperative interventions that nearly all patients are exposed to in the setting of surgery. Gut microbial dysbiosis has been postulated to be a risk factor for poor surgical outcomes, but how perioperative care-independent of the surgical intervention-impacts the gut microbiome, and the potential consequences of this impact have not been directly investigated.<br><br>METHODS: We developed a perioperative exposure model (PEM) in C57Bl/6 mice to emulate the most common elements of perioperative medicine other than surgery, which included 12 hours of nutritional deprivation, 4 hours of volatile general anesthetic, 7 hours of supplemental oxygen, surgical antibiotics (cefazolin), and opioid pain medication (buprenorphine). Gut microbial dynamics and inferred metabolic changes were longitudinally assessed before-and at 3 time points after-PEM by 16S rRNA amplicon sequencing. We then used fecal microbial transplant in secondary abiotic mice to test if, compared to preexposure microbiota, day 3 post-PEM microbial communities affect the clinical response to immune challenge in an endotoxemia model.<br><br>RESULTS: We observed transient changes in microbiota structure and function after the PEM, including reduced biodiversity, loss of diverse commensals associated with health (including Lactobacillus, Roseburia, and Ruminococcus), and changes in microbiota-mediated amino acid metabolic pathways. Mice engrafted with day 3 post-PEM microbial communities demonstrated markedly reduced survival after endotoxemia compared to those bearing preexposure communities (7-day survival of ~20% vs ~70%, P = .0002).<br><br>CONCLUSIONS: These findings provide the first clear evidence that the combined effects of common perioperative factors, independent of surgery, cause gut microbial dysbiosis and alter the host response to inflammation in the postoperative period.}, }
@article {pmid40062406, year = {2025}, author = {Moutsoglou, D and Ramakrishnan, P and Vaughn, BP}, title = {Microbiota transplant therapy in inflammatory bowel disease: advances and mechanistic insights.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2477255}, pmid = {40062406}, issn = {1949-0984}, mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/microbiology/immunology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {Microbiota transplant therapy is an emerging therapy for inflammatory bowel disease, but factors influencing its efficacy and mechanism remain poorly understood. In this narrative review, we outline key elements affecting therapeutic outcomes, including donor factors (such as age and patient relationship), recipient factors, control selection, and elements impacting engraftment and its correlation with clinical response. We also examine potential mechanisms through inflammatory bowel disease trials, focusing on the interplay between the microbiota, host, and immune system. Finally, we briefly explore potential future directions for microbiota transplant therapy and promising emerging treatments.}, }
@article {pmid40061173, year = {2025}, author = {Borah, P and Gautam, V and Kumar, V and Saikia, B and Naithani, R}, title = {Fecal Microbiota Transplantation for Refractory Clostridioides difficile Infection Post Haploidentical Transplant for Pediatric Acute Myeloid Leukemia.}, journal = {Blood cell therapy}, volume = {8}, number = {1}, pages = {170-172}, pmid = {40061173}, issn = {2432-7026}, abstract = {BACKGROUND: Clostridioides difficile (C. difficile) infections are common in immunosuppressed patients. Sometimes these are difficult to treat in post-bone marrow transplant situations.<br><br>METHODS: A 2-year-old child with relapsed acute myeloid leukemia underwent a haploidentical bone marrow transplant. He developed 30-40 episodes/day of loose watery stools on day +19. The stool was positive for C. difficile infection. He failed oral vancomycin and metronidazole therapy. He received a fecal microbiota transplant (FMT) on day +43. The donor was the same sister who donated hematopoietic stem cells.<br><br>RESULTS: Three days later (day +46), stool frequency reduced from 22-24/day to 12-14/day. Color normalized to yellow and consistency improved from watery to semisolid without blood. He was discharged from the hospital 10 days after FMT on oral vancomycin and nasogastric feeding. Stool tested for C. difficile 16 days after FMT was negative and oral vancomycin was stopped.<br><br>CONCLUSION: Fecal microbiota transplant could be a useful modality in children with severe C. difficile infection post-bone marrow transplant.}, }
@article {pmid40060755, year = {2025}, author = {Yi, D and Li, T and Xiao, Y and Zhang, X and Hao, Q and Zhang, F and Qiu, T and Yang, G and Sun, X and Dong, Y and Wang, N}, title = {Fecal microbiota transplantation for the treatment of intestinal and extra-intestinal diseases: Mechanism basis, clinical application, and potential prospect.}, journal = {Bioengineering &amp; translational medicine}, volume = {10}, number = {2}, pages = {e10728}, pmid = {40060755}, issn = {2380-6761}, abstract = {To review the theoretical basis and therapeutic effects of fecal microbiota transplantation (FMT) in various diseases in animal experiments and clinical studies, as well as the limitations and current standards of FMT application. PubMed and Web of Science databases were searched for articles published only in English between 1975 and 2023 on reliable results of animal experiments and clinical treatment of FMT. The properties of the gut microbiota and its interactions with the host metabolism are critical to human health, and microbiome disturbance is closely associated with human intestinal and extra-intestinal diseases. Therefore, therapeutic tools targeting on the modulation of gut microbiota have attracted increasing attention, among which FMT represents the most widely studied intervention strategy. This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis, and elaborated the beneficial effects that can be achieved by altering the microbiota with FMT and the mechanisms of action. In addition, the potential risks and side effects of FMT approach are discussed, as well as current efforts to standardize the development of FMT. Through a systemic review of the outcome and mechanism of FMT in the treatment of intestinal diseases and extra-intestinal diseases, we aimed to provide a theoretical basis for the construction of an optimized FMT framework, so as to better exert its application prospects.}, }
@article {pmid40060387, year = {2025}, author = {Kim, M and Wang, J and Pilley, SE and Lu, RJ and Xu, A and Kim, Y and Liu, M and Fu, X and Booth, SL and Mullen, PJ and Benayoun, BA}, title = {Estropausal gut microbiota transplant improves measures of ovarian function in adult mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40060387}, issn = {2692-8205}, support = {P30 CA014089/CA/NCI NIH HHS/United States ; R24 HD102061/HD/NICHD NIH HHS/United States ; T32 AG052374/AG/NIA NIH HHS/United States ; }, abstract = {Decline in ovarian function with age not only affects fertility but is also linked to a higher risk of age-related diseases in women (e.g. osteoporosis, dementia). Intriguingly, earlier menopause is linked to shorter lifespan; however, the underlying molecular mechanisms of ovarian aging are not well understood. Recent evidence suggests the gut microbiota may influence ovarian health. In this study, we characterized ovarian aging associated microbial profiles in mice and investigated the effect of the gut microbiome from young and estropausal female mice on ovarian health through fecal microbiota transplantation. We demonstrate that the ovarian transcriptome can be broadly remodeled after heterochronic microbiota transplantation, with a reduction in inflammation-related gene expression and trends consistent with transcriptional rejuvenation. Consistently, these mice exhibited enhanced ovarian health and increased fertility. Using metagenomics-based causal mediation analyses and serum untargeted metabolomics, we identified candidate microbial species and metabolites that may contribute to the observed effects of fecal microbiota transplantation. Our findings reveal a direct link between the gut microbiota and ovarian health.}, }
@article {pmid40058319, year = {2025}, author = {Zhang, W and Yi, C and Song, Z and Yu, B and Jiang, X and Guo, L and Huang, S and Xia, T and Huang, F and Yan, Y and Li, H and Dai, Y}, title = {Reshaping the gut microbiota: Tangliping decoction and its core blood-absorbed component quercetin improve diabetic cognitive impairment.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {140}, number = {}, pages = {156560}, doi = {10.1016/j.phymed.2025.156560}, pmid = {40058319}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Quercetin/pharmacology ; Animals ; *Cognitive Dysfunction/drug therapy ; *Drugs, Chinese Herbal/pharmacology ; Mice ; Male ; *Diabetes Mellitus, Type 2/drug therapy ; *Diabetes Mellitus, Experimental/drug therapy ; RNA, Ribosomal, 16S ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive decline, which can result in diabetic cognitive impairment (DCI). Recent studies have indicated that gut microbiota plays a significant role in the development of DCI. Tangliping Decoction (TLP), a traditional Chinese medicine compound, contains various active ingredients that have been shown to regulate the microecology of gut microbiota and potentially improve DCI. However, it remains unclear whether TLP can improve DCI by modulating gut microbiota, as well as which specific component is primarily responsible for these effects.<br><br>PURPOSE: Assess the impact of TLP on alleviating DCI and investigate the contribution of quercetin (QR), the core blood-absorbed component of TLP, in this process. and investigate the underlying mechanisms through which TLP and QR enhance DCI by modulating gut microbiota composition.<br><br>STUDY DESIGN AND METHODS: Initially, experiments such as morris water maze (MWM), morphological analysis, and 16S ribosomal RNA (16S rRNA) gene amplicon sequencing from DCI mice, were performed to validate the pharmacological efficacy of TLP in mitigating DCI. The results indicated that TLP possesses the capacity to modulate the composition and quantity of gut microbiota and safeguard the integrity of the gut barrier and brain barrier. Secondly, high performance liquid chromatography coupled with high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) combined with network pharmacology methods were used to screen for blood-absorbed components, suggesting that QR may be a potential core blood-absorbed component of TLP in the treatment of DCI. Subsequently, the pharmacological efficacy of QR in ameliorating DCI was confirmed, and the characteristics of gut microbiota as well as the permeability of the gut and brain barrier, were assessed. Finally, fecal microbiota transplantation (FMT) experiments were conducted, wherein fecal matter from TLP and QR-treated mice (donor mice) was transplanted into pseudo-sterile DCI mice with antibiotic-induced depletion of gut microbiota. This approach aimed to elucidate the specific mechanisms by which TLP and QR improve DCI through the modulation of the structure, composition, and abundance of gut microbiota.<br><br>RESULTS: TLP and QR have the potential to enhance learning and memory capabilities in DCI mice, as well as reduce homeostasis model assessment insulin resistance (HOMA-IR) and restore homeostasis model assessment-&#x3b2; function (HOMA- &#x3b2;), leading to increased fasting insulin (FIN) levels and decreased fasting blood glucose (FBG) levels. Simultaneously, the administration of FMT from donor mice to pseudo-sterile DCI mice has been shown to alter the composition and abundance of gut microbiota, leading to amelioration of pathological damage in the colon and hippocampal tissues. Ultimately, FMT utilizing fecal suspensions from donor mice treated with TLP and QR improved cognitive function in pseudo-sterile DCI mice, restore gut microbiota dysbiosis, and maintained the integrity of the gut and brain barriers.<br><br>CONCLUSION: The results of this study indicate that TLP and its core component, QR, which is absorbed into the bloodstream, improve DCI through a gut microbiota-dependent mechanism, providing further evidence for gut microbiota as a therapeutic target for DCI treatment.}, }
@article {pmid40058316, year = {2025}, author = {Tang, X and Huang, L and Ma, W and Huang, M and Zeng, Z and Yu, Y and Qin, N and Zhou, F and Li, F and Gong, S and Yang, H}, title = {Intestinal 8 gingerol attenuates TBI-induced neuroinflammation by inhibiting microglia NLRP3 inflammasome activation in a PINK1/Parkin-dependent manner.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {140}, number = {}, pages = {156580}, doi = {10.1016/j.phymed.2025.156580}, pmid = {40058316}, issn = {1618-095X}, mesh = {Animals ; *Fatty Alcohols/pharmacology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Catechols/pharmacology ; Male ; *Ubiquitin-Protein Ligases/metabolism ; *Brain Injuries, Traumatic/drug therapy ; *Inflammasomes/metabolism/drug effects ; *Microglia/drug effects ; *Neuroinflammatory Diseases/drug therapy ; *Protein Kinases/metabolism ; Rats ; *Gastrointestinal Microbiome/drug effects ; *Rats, Sprague-Dawley ; Dysbiosis/drug therapy ; Fecal Microbiota Transplantation ; Mice ; Mitophagy/drug effects ; Disease Models, Animal ; }, abstract = {BACKGROUND: traumatic brain injury (TBI) is irreversible brain damage, leading to inflammation and cognitive dysfunction. Microglia involved in the inflammatory response after TBI. The gut microbiota, known as the body's "second brain," regulates neurogenesis and immune responses, but its precise role in regulating TBI remains unclear.<br><br>PURPOSE: to investigate the effect of gut microbiota and metabolites disorder on TBI injury.<br><br>STUDY DESIGN: 16SrRNA and metabolomics compared gut microbiota and metabolites in sham group and TBI group, then proved that the differential metabolite 8-gingerol (8G) alleviated the microglia neuroinflammatory response after TBI.<br><br>METHODS: fecal microbiota transplantation explored the role of dysbiosis in TBI. LC/MS detected the content of 8-gingerol in cecum, blood, and brain. HE, Nissl, Tunel staining and mNSS score evaluated brain injury. Western blot and immunofluorescence detected the expression of inflammasome-related proteins and mitophagy-related proteins in brain tissue and BV2 cells. RNA sequencing analyzed the molecular mechanism of 8-gingerol.<br><br>RESULT: rats transplanted with TBI feces had worse brain injury and neurological deficits than those with normal feces. 16SrRNA and metabolomics found that TBI caused dysbiosis and decreased 8-gingerol level, leading to severe neuroinflammation. Mechanistically, 8-gingerol inhibited NLRP3 inflammasome by promoting PINK1-Parkin mediated mitophagy in microglia. Inhibition of Parkin, through either small interfering RNA or the inhibitor 3MA reversed the inhibitory effect of 8-gingerol on NLRP3 by blocking mitophagy. BV2 cells transcriptome showed that 8-gingerol significantly increased the expression of autophagy factor Wipi1, and small interfering RNA of Wipi1 abolished the effect of 8-gingerol on promoting mitophagy and the inhibitory effect on NLRP3.<br><br>CONCLUSION: our findings shed light on the pivotal role of gut microbes in TBI, and identify 8 gingerol as an important anti-inflammatory compound during TBI.}, }
@article {pmid40058066, year = {2025}, author = {Mu, X and Feng, L and Wang, Q and Li, H and Zhou, H and Yi, W and Sun, Y}, title = {Decreased gut microbiome-derived indole-3-propionic acid mediates the exacerbation of myocardial ischemia/reperfusion injury following depression via the brain-gut-heart axis.}, journal = {Redox biology}, volume = {81}, number = {}, pages = {103580}, pmid = {40058066}, issn = {2213-2317}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Depression/metabolism/microbiology ; *Myocardial Reperfusion Injury/metabolism/etiology/pathology ; *Indoles ; Male ; *Brain-Gut Axis ; Disease Models, Animal ; }, abstract = {Despite the increasing recognition of the interplay between depression and cardiovascular disease (CVD), the precise mechanisms by which depression contributes to the pathogenesis of cardiovascular disease remain inadequately understood. The involvement of gut microbiota and their metabolites to health and disease susceptibility has been gaining increasing attention. In this study, it was found that depression exacerbated cardiac injury, impaired cardiac function (EF%: P < 0.01; FS%: P < 0.05), hindered long-term survival (P < 0.01), and intensified adverse cardiac remodeling (WGA: P < 0.01; MASSON: P < 0.0001) after myocardial ischemia/reperfusion (MI/R) in mice. Then we found that mice receiving microbiota transplants from chronic social defeat stress (CSDS) mice exhibited worse cardiac function (EF%: P < 0.01; FS%: P < 0.01) than those receiving microbiota transplants from non-CSDS mice after MI/R injury. Moreover, impaired tryptophan metabolism due to alterations in gut microbiota composition and structure was observed in the CSDS mice. Mechanistically, we analyzed the metabolomics of fecal and serum samples from CSDS mice and identified indole-3-propionic acid (IPA) as a protective agent for cardiomyocytes against ferroptosis after MI/R via NRF2/System xc-/GPX4 axis, played a role in mediating the detrimental influence of depression on MI/R. Our findings provide new insights into the role of the gut microbiota and IPA in depression and CVD, forming the basis of intervention strategies aimed at mitigating the deterioration of cardiac function following MI/R in patients experiencing depression.}, }
@article {pmid40055837, year = {2025}, author = {Alexandra, P and Noémie, P and Solène, SB and Jean-Benoit, H and Riche, VP and Odile, C and Michel, G and Guy, V and Hamy, A and Mehdi, O and Yannick, T and Jeremie H, L and Amar, A and Emeric, A and Jean-Michel, B and Bridoux, V and Dumont, F and June, F and Alexandra, J and Meurette, G and Duchalais, E}, title = {Evaluation of pelvic floor rehabilitation in the prevention of low anterior resection syndrome: Study protocol of the CONTICARE trial.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {27}, number = {3}, pages = {e70045}, doi = {10.1111/codi.70045}, pmid = {40055837}, issn = {1463-1318}, support = {//French Ministry of Health (PHRCI 2016 - API16/N/055)/ ; }, mesh = {Humans ; *Pelvic Floor/physiopathology ; *Rectal Neoplasms/surgery/rehabilitation ; *Postoperative Complications/prevention &amp; control/rehabilitation ; Syndrome ; Female ; *Quality of Life ; *Proctectomy/adverse effects/methods/rehabilitation ; *Fecal Incontinence/etiology/prevention &amp; control/rehabilitation ; Biofeedback, Psychology/methods ; Randomized Controlled Trials as Topic ; Male ; Anal Canal/surgery ; Middle Aged ; Adult ; Multicenter Studies as Topic ; Treatment Outcome ; Aged ; Exercise Therapy/methods ; Low Anterior Resection Syndrome ; }, abstract = {AIM: Bowel dysfunction following sphincter-preserving rectal resection for cancer, commonly referred to as low anterior resection syndrome (LARS), significantly impacts patients' quality of life. Preventing this condition is essential for healthcare teams. Postoperative pelvic floor rehabilitation, including anal biofeedback therapy, has shown potential in alleviating established LARS symptoms. This trial aims to evaluate the effectiveness of pelvic floor rehabilitation prior to bowel continuity restoration in preventing LARS in patients undergoing sphincter-preserving rectal resection for cancer.<br><br>METHODS: CONTICARE is a national multicentre randomized trial. Patients who have undergone total mesorectal excision with sphincter preservation and a defunctioning stoma (n&#x2009;=&#x2009;174; 87 per arm) will be randomly assigned to either the rehabilitation or control group before stoma closure. The rehabilitation group will receive systematic pelvic floor rehabilitation, comprising four sessions before and six sessions after stoma closure, following a standardized approach. The control group will receive standard follow-up care, which includes symptom-based therapy after ileostomy closure. The primary outcome measure will be the severity of LARS, assessed using the dedicated LARS score at 6&#x2009;months. Comparisons of faecal incontinence symptoms, quality of life and complications related to biofeedback therapy will also be evaluated at 6&#x2009;weeks, 6&#x2009;months and 1&#x2009;year between the two groups.<br><br>CONCLUSION: Pelvic floor rehabilitation has the potential to enhance symptom management and quality of life for patients following rectal resection by preventing LARS. The combination of anal exercises and biofeedback therapy, which has been extensively studied without reported adverse effects, suggests that the anticipated benefits outweigh any potential risks.<br><br>CLINICAL TRIAL REGISTRATION: Registration number NCT03876561, first published on 15 March 2019.<br><br>CLINICALTRIALS: gov.}, }
@article {pmid40054499, year = {2025}, author = {Luan, WW and Gu, HW and Qiu, D and Ding, X and Liu, PM and Hashimoto, K and Yang, JJ and Wang, XM}, title = {Repeated administration of esketamine ameliorates mechanical allodynia in mice with chemotherapy-induced peripheral neuropathy: A role of gut microbiota and metabolites.}, journal = {Neurochemistry international}, volume = {185}, number = {}, pages = {105961}, doi = {10.1016/j.neuint.2025.105961}, pmid = {40054499}, issn = {1872-9754}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; *Ketamine/administration &amp; dosage/pharmacology ; *Hyperalgesia/drug therapy/metabolism/chemically induced ; Oxaliplatin/toxicity ; Male ; *Peripheral Nervous System Diseases/chemically induced/drug therapy/metabolism ; *Antineoplastic Agents/toxicity ; Mice, Inbred C57BL ; }, abstract = {Chemotherapy-induced peripheral neuropathy (CIPN) severely diminishes the quality of life for cancer survivors, yet effective treatments remain scarce. Esketamine, a commonly used anesthetic, has demonstrated neuroprotective effects by restoring gut microbiome dysbiosis. In this study, we investigated the impact of esketamine on nociceptive sensitivity in a mouse model of CIPN and explored the potential involvement of the gut microbiome. In mice treated with oxaliplatin, repeated esketamine doses (in contrast to a single dose) significantly improved the paw withdrawal threshold (PWT). Western blot and qPCR analyses further revealed that repeated esketamine administration markedly reduced microglial activation and neuroinflammation in the dorsal root ganglion (DRG), underscoring its potent anti-inflammatory properties. Moreover, fecal 16S rRNA analysis indicated that esketamine partially restored the abnormal gut microbiota composition (β-diversity). Plasma metabolome analysis showed that repeated esketamine treatment significantly lowered the elevated levels of 6H-indolo[2,3-b]quinoline and restored the reduced levels of (3-exo)-3-[3-methyl-5-(1-methylethyl)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]octane observed in oxaliplatin-treated mice. In addition, fecal microbiota transplantation from esketamine-treated CIPN mice notably improved both the diminished PWT and DRG neuroinflammation in oxaliplatin-treated mice. Collectively, these findings suggest that repeated esketamine administration may alleviate mechanical allodynia in CIPN mice by modulating neuroinflammation, gut microbiota, and associated metabolites.}, }
@article {pmid40053245, year = {2025}, author = {Lukic, I and Ivkovic, S and Glavonic, E and Adzic, M and Mitic, M}, title = {Long-lasting Depressive Behavior of Adolescent Chronically Stressed Mice is Mediated by Gut Microbiota Dysbiosis.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40053245}, issn = {1559-1182}, abstract = {Depression is one of the most common mental disorders worldwide, and its prevalence sharply rises during adolescence. Adolescence is a particularly sensitive period to the effects of environmental stressors, which can cause persistent depressive behavior extending into adulthood. However, the studies assessing if changes in gut microbiota could be one of the mediators of long-term effects of adolescent stress are scarce. In the present study, we examined enduring effects of adolescent chronic unpredictable stress (CUS) on mice behavior along with alterations in their gut microbiome, by using 16 s rRNA gene sequencing and fecal microbiota transplantation (FMT). CUS mice, as well as naïve mice receiving FMT from stressed animals, showed long-lasting anxiety and depressive-like behavior extending into adulthood. The microbiota dysbiosis in adolescence was characterized by higher abundance of Alloprevotella and lower abundance of Paraprevotella, Parasutterella, Parabacteroides, and undefined genus Rikenellaceae_RC9_gut_group. On the contrary, microbiota dysbiosis in adulthood was characterized by higher abundance of Bacteroides, Enterorhabdus, Marvinbriantia, and Parabacteroides and lower abundance of Akkermansia, Odoribacter, and Rikenella. In particular, depressive-like behavior in adolescence was negatively correlated with Paraprevotella, while depressive-like behavior in adulthood was negatively correlated with Rikenella abundance, in both CUS and FMT mice. Therefore, the transfer of microbiota from mice stressed in adolescence is able to induce long-lasting depressive-like behavior in naïve mice, clearly showing the importance of gut microbiota dysbiosis in adolescence in shaping enduring depressive behavior. Moreover, our results indicate that changes in specific but different bacteria are related to depressive behavior in adolescence and in adulthood.}, }
@article {pmid40051947, year = {2025}, author = {Bhalla, A and Shahi, A and Maity, M and Safa, F and Srividya, V and Clementina, R and Anugu, GR and Younas, S}, title = {Inflammatory Bowel Disease in Children: Current Diagnosis and Treatment Strategies.}, journal = {Cureus}, volume = {17}, number = {2}, pages = {e78462}, pmid = {40051947}, issn = {2168-8184}, abstract = {Pediatric inflammatory bowel disease (PIBD), including Crohn's disease and ulcerative colitis, has emerged as a significant global health challenge with rising incidence rates. Unlike adult inflammatory bowel disease, PIBD presents complexities, including growth impairment, nutritional deficiencies, and psychosocial challenges that necessitate tailored management strategies. This article reviews current diagnostic and emerging treatment strategies to highlight the evolution from traditional therapies such as aminosalicylates, corticosteroids, and immunomodulators to advanced biologic agents like infliximab and adalimumab. Emerging biological therapies, including vedolizumab and ustekinumab, show promise, while novel small molecule therapies such as Janus kinase (JAK) inhibitors are under investigation for potential use in the pediatric population. Supportive treatments, including exclusive enteral nutrition, modified diets, and probiotics, play a critical role in comprehensive disease management. Stem cell therapy and fecal microbiota transplant represent innovative approaches still under clinical evaluation. The review underscores the significance of holistic care, incorporating mind-body interventions and psychosocial support to improve patient quality of life. Key challenges persist, such as infection risks associated with long-term biological therapy use, gaps in pediatric-specific guidelines, and the limited inclusion of children in clinical trials. Future recommendations emphasize the importance of structured transition programs bridging pediatric and adult care, regular updates to clinical guidelines, and the integration of precision medicine to personalize treatment plans. Continued research and collaboration are essential for advancing the understanding and management of PIBD, ensuring that pediatric patients benefit from the most effective, evidence-based care available.}, }
@article {pmid40050917, year = {2025}, author = {Zou, B and Liu, S and Dong, C and Shen, H and Lv, Y and He, J and Li, X and Ruan, M and Huang, Z and Shu, S}, title = {Fecal microbiota transplantation restores gut microbiota diversity in children with active Crohn's disease: a prospective trial.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {288}, pmid = {40050917}, issn = {1479-5876}, mesh = {Humans ; *Crohn Disease/therapy/microbiology ; Child ; Female ; Male ; Prospective Studies ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Adolescent ; Biodiversity ; Feces/microbiology ; Biomarkers/metabolism ; Treatment Outcome ; }, abstract = {BACKGROUND: Clinical data on oral fecal microbiota transplantation (FMT), a promising therapy for Crohn's disease (CD), are limited. Herein, we determined the short-term safety and feasibility of FMT for pediatric patients with active CD.<br><br>METHODS: In this open-label, parallel-group, single-center prospective trial, patients with active CD were treated with oral FMT capsules combined with partial enteral nutrition (PEN) (80%). The control group comprised pediatric patients with active CD treated with PEN (80%) and immunosuppressants. Thirty-three patients (11.6&#x2009;&#xb1;&#x2009;1.82&#xa0;years)-17 in the capsule and 16 in the control groups-were analyzed. Data regarding the adverse events, clinical reactions, intestinal microbiome composition, and biomarker parameters were collected and compared post-treatment.<br><br>RESULTS: At week 10, the clinical and endoscopic remission rates did not differ between the two groups. By week 10, the mean fecal calprotectin level, C-reactive protein level, erythrocyte sedimentation rate, simple endoscopic score for CD, and pediatric CD activity index decreased significantly in the capsule group (all P&#x2009;<&#x2009;0.05). The main adverse event was mild-to-moderate constipation. Core functional genera, Agathobacter, Akkermansia, Roseburia,&#xa0;Blautia, Subdoligranulum, and Faecalibacterium, were lacking pre-treatment. Post-treatment, the implantation rates of these core functional genera increased significantly, which positively correlated with the anti-inflammatory factor, interleukin (IL)-10, and negatively correlated with the pro-inflammatory factor, IL-6. The combination of these six functional genera distinguished healthy children from those with CD (area under the curve&#x2009;=&#x2009;0.96).<br><br>CONCLUSIONS: Oral FMT capsules combined with PEN (80%) could be an effective therapy for children with active CD. The six core functional genera identified here may be candidate biomarkers for identifying children with CD.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, retrospectively registered, ID# NCT05321758, NCT05321745, date of registration: 2022-04-04.}, }
@article {pmid40050761, year = {2025}, author = {Salazar-Arenas, JA and Hurtado-Bermúdez, LJ and Salazar-Cardona, ED and Rojas-Rojas, NE and Cubides-Martinez, JF and Toro-Palma, JD and Zúñiga-Restrepo, V and Rojas-Rodríguez, CA}, title = {Clinical and microbiological profile of patients with diarrhea evaluated using the gastrointestinal panel in a high-complexity center.}, journal = {BMC gastroenterology}, volume = {25}, number = {1}, pages = {147}, pmid = {40050761}, issn = {1471-230X}, mesh = {Humans ; *Diarrhea/microbiology/epidemiology ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Colombia/epidemiology ; *Immunocompromised Host ; Adult ; Aged ; Feces/microbiology/parasitology ; Young Adult ; }, abstract = {INTRODUCTION: Gastrointestinal infections represent a worldwide public health problem. In Colombia, the incidence reaches 21.4 cases per 1,000 inhabitants. Given the limitations of traditional diagnostic methods in terms of sensitivity and specificity, the gastrointestinal panel (GIP) has emerged as a promising tool, allowing rapid detection of 22 pathogens. This study aimed to describe the clinical and microbiological characteristics of immunosuppressed and immunocompetent adult patients with diarrhea and the influence of the gastrointestinal panel in their treatment in a high-complexity hospital in Colombia.<br><br>MATERIALS AND METHODS: A cross-sectional observational study was carried out including 350 adult patients treated at the Fundaci&#xf3;n Valle del Lili hospital between 2021 and 2022. Demographic and clinical variables, GIP findings and treatment were analyzed by univariate and bivariate analysis. We compare immunocompromised and immunocompetent adult patients using Chi-square tests, Fisher's F test for qualitative variables, Student's t-test, and the Mann-Whitney U test for quantitative variables. A significance level of 5% was applied to demonstrate the significance of the variables in all the tests used.<br><br>RESULTS: The results showed that 52% were men, with an average age of 52 years. 72.0% presented acute diarrhea, being inflammatory in 60.1%. 39.1% of the patients were immunosuppressed, mainly transplant recipients (31.3%). 53% of the GIPs were positive, with up to 5 pathogens per sample. Bacteria were detected in 80%, viruses in 14.4%, and parasites in 5.5%. The most frequent bacteria were enteropathogenic E. coli (43.0%), enteroaggregative E. coli (18.6%), and C. difficile (17.4%). Norovirus was the predominant virus (67.7%) and Cryptosporidium the most common parasite (41.7%). A higher frequency of Vibrio spp. was observed in non-immunosuppressed patients (p&#x2009;=&#x2009;0.004) and of enterotoxigenic E. coli in immunosuppressed patients. 41.0% of patients received antibiotic/antiviral therapy, 83% empirically. GIP influenced the treatment of 56.7% of patients, with a 90.0% recovery rate.<br><br>CONCLUSION: This study confirms that GIP is a valuable diagnostic tool in the management of adult patients with diarrheal disease, particularly in immunocompromised patients. In our setting it is still a costly and difficult to access test, which makes it necessary to standardize the indications for its application. Future studies could evaluate its cost-effectiveness in our context.}, }
@article {pmid40049043, year = {2025}, author = {Huang, JN and Gao, CC and Ren, HY and Wen, B and Wang, ZN and Gao, JZ and Chen, ZZ}, title = {Multi-omics association pattern between gut microbiota and host metabolism of a filter-feeding fish in situ exposed to microplastics.}, journal = {Environment international}, volume = {197}, number = {}, pages = {109360}, doi = {10.1016/j.envint.2025.109360}, pmid = {40049043}, issn = {1873-6750}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Microplastics ; *Water Pollutants, Chemical/metabolism/toxicity ; *Carps/microbiology ; Liver/metabolism ; Zebrafish ; Multiomics ; }, abstract = {Microplastics (MPs) are widespread in water environments and can affect gut microbiota and host metabolism of fish, but whether changes in host metabolism under MPs are mediated by gut microbiota remains unclear. Here, silver carp, a filter-feeding fish with important ecological functions, was in-situ exposure to environmentally relevant MPs. Multi-omics analysis and fecal microbiota transplantation were used to reveal the metabolic responses of carp along gut-liver-muscle axis. After three months of in situ exposure to MPs, community structure of gut microbiota of carp was reshaped, and five dominate phyla were significantly changed, including increased Cyanobacteria, Chloroflexi and Planctomycetota but decreased Firmicutes and Fusobacteriota. Weighted gene co-expression network analysis was further performed between these phyla and liver transcription spectrum, showing that the hub gene module contained up-regulated hppD, maiA and plg and activated ubiquinone and other terpenoid-quinone biosynthesis and phenylalanine metabolism. By fecal microbiota transplantation, the key gene module associated with core microbiota phyla of carp was verified in germ-free zebrafish. Interestingly, up-regulated hppD, maiA and plg and enriched phenylalanine metabolism were also observed in this module. Subsequently, metabolome performed in carp liver also shared activated phenylalanine metabolism, including increased trans-cinnamic acid and L-tyrosine. Furthermore, high-associated mapping showed that the differentially expressed metabolites (gamma-aminobutyric acid, ornithine and L-serine) related to amino acid metabolism in carp muscle were significantly accompanied with increased L-tyrosine in its liver. Overall, MPs exposure could change gut microbiome of silver carp and alter host metabolism especially amino acid metabolism along the gut-liver-muscle axis.}, }
@article {pmid40047909, year = {2025}, author = {Heinze, T and Heimke, M and Stelzner, S and Wedel, T}, title = {[Surgical anatomy of the anorectum].}, journal = {Chirurgie (Heidelberg, Germany)}, volume = {96}, number = {5}, pages = {431-444}, pmid = {40047909}, issn = {2731-698X}, mesh = {Humans ; *Anal Canal/anatomy &amp; histology/surgery/blood supply/innervation ; *Rectum/anatomy &amp; histology/surgery/blood supply/innervation ; }, abstract = {The anorectum corresponds to the last segment of the gastrointestinal tract and is responsible for mediating fecal continence and controlled defecation. An understanding of the complex topographic anatomy is an indispensable prerequisite for the surgical treatment of benign and malignant diseases in the anorectal region. The detailed description of perirectal fascia, anorectal blood supply and lymph vessel drainage, pelvic autonomic nerves and components of the anal canal and anal sphincter complex has significantly contributed to improvement of the oncological and functional surgical outcome. In this article the state of knowledge relating to the anorectal anatomy is outlined providing a practical basis for rectal and proctological surgical procedures.}, }
@article {pmid40046764, year = {2025}, author = {Hou, PF and Yao, Y and Wu, Y and Yu, HT and Qin, Y and Yi, L and Mi, MT}, title = {Fecal microbiota transplantation improves hepatic steatosis induced by HFD in a mouse model associated with liver ILC1 regulation and indole-3-carbinol level.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1500293}, pmid = {40046764}, issn = {2296-861X}, abstract = {BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased worldwide. In recent years, fecal microbiota transplantation (FMT) has become an important promising method for the treatment of MASLD. However, the mechanism remains unclear.<br><br>METHODS: The animal model with C57BL/6 male mice induced by high-fat diet (HFD) for 12 weeks has been introduced. Fecal microbiota and indole-3-carbinol (I3C) was given by oral gavage.<br><br>RESULTS: Our study demonstrated that a 6-week healthy gut microbiota transplantation tended to ameliorate hepatic steatosis and reverse the decreased liver ILC1 induced by HFD. Interestingly, there was also a negative correlation between liver ILC1 and liver TG, TC level. Furthermore, the protective effect was associated with the elevated levels of serum indole-3-carbinol (I3C). Also, a I3C administration for 6 weeks improved liver steatosis and increased the frequency of liver ILC1 induced by HFD through aryl hydrocarbon receptor (AhR) activation. Moreover, I3C binds to the residues of ALA349, PHE348, LEU309, TYR316, PHE318 on AhR through hydrogen bonds, &#x3a0; bonds, hydrophobic bonds which was proved by molecular docking.<br><br>CONCLUSION: To conclude, our data demonstrated that FMT improved liver steatosis induced by HFD associated with liver ILC1 regulation and indole-3-carbinol level. The study highlighted the potential treatment value of FMT and microbiota-derived I3C in the MASLD treatment and regulation of liver ILC1 function.}, }
@article {pmid40046008, year = {2024}, author = {Zeng, Z and Feng, M and He, F and Zhang, E and Li, X and Cao, Z}, title = {Gut microbiota mediates the pro-pyroptosis effect of xierezhuyubuxu decoction in hepatocellular carcinoma.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1481111}, pmid = {40046008}, issn = {1664-302X}, abstract = {INTRODUCTION: Xierezhuyubuxu decoction (XRZYBXD) is prepared by adding and reducing the Dahuang Zhechong Pill, which is a traditional Chinese medicinal formula in "The Synopsis of Prescriptions of the Golden Chamber". XRZYBXD has previously been reported to have good efficacy in treating Hepatocellular carcinoma (HCC) in clinical and basic research. However, its underlying mechanism in treating HCC has not been fully elucidated. The aim of the study is to investigate the pro-pyroptosis effect of XRZYBXD in HCC and the role of gut microbiota in this process.<br><br>METHODS: Firstly, we executed comprehensive analyses of XRZYBXD on pyroptosis, intestinal flora, microbial metabolites and intestinal barrier function using TUNEL, IHC, ELISA, WB, Q-PCR, 16S rRNA sequencing, and untargeted metabolomics in a H22 tumor-bearing mice model. Further, through rescue experiment of antibiotics-induced microbiota depletion and fecal microbial transplantation (FMT) experiment, the mechanism of XRZYBXD promoting pyroptosis of HCC by improving intestinal flora was verified.<br><br>RESULTS: We found that XRZYBXD medium and high dose significantly inhibited the growth of tumor and induced pyroptosis of hepatoma cells. They also modified intestinal ecological disorders by expansion of the abundance of beneficial bacteria (such as Akkermansia muciniphila and Parabacteroides distasonis) and reduction of the abundance of harmful bacteria (such as Barnesiella intestinihominis). Accordingly, microbiota metabolites and intestinal barrier function were also significantly improved by XRZYBXD.<br><br>DISCUSSION: Further, elimination of gut microbiota by antibiotics weakened the efficacy of XRZYBXD, and FMT with feces from the XRZYBXD high dose group achieved similar therapeutic efficacy as XRZYBXD. In brief, XRZYBXD promote pyroptosis of hepatoma cells via adjusting intestinal dysbiosis.}, }
@article {pmid40045660, year = {2025}, author = {Hu, J and Xu, F and Zhu, L and Cui, Y and Au, R and Li, Y and Tong, Y and Shen, H}, title = {Angelica dahurica Polysaccharides Ameliorate Colitis by Reducing the Restriction of Gut Microbiota-Derived Imidazole Propionate on PPAR-γ Signaling Activation.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.8466}, pmid = {40045660}, issn = {1099-1573}, support = {82205023//National Natural Science Foundation of China/ ; 82274483//National Natural Science Foundation of China/ ; }, abstract = {Angelica dahurica radix (ADR), the root of the botanical family Apiaceae (genus Angelica, species Angelica dahurica (Hoffm.)), has been used to treat colitis in clinical practice. The immunomodulatory effects of ADR are attributed to its polysaccharides (RP). However, its mechanism of action has not been elucidated. In this study, RP's structure was determined through nuclear magnetic resonance analysis. Dextran sulfate sodium-induced colitis in mice was utilized to assess the therapeutic efficacy of RP, while experiments involving fecal microbiota transplantation (FMT) and antibiotic treatment were performed to investigate the contribution of gut microbiota to RP's protective function. Non-targeted metabolomics was utilized to identify potential targets for elucidating the underlying mechanisms. RP is likely composed of (→4)-α-D-Glcp-(1→ and →4)-α-D-Galp-(1→). It effectively alleviated DSS-induced colitis by restoring the balance of the gut microbial community, a finding validated through FMT and antibiotic intervention experiments. Imidazole propionate (ImP) emerged as a potential target for RP's efficacy in treating colitis, which inhibits the activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). Our findings suggest that RP may confer protection against colitis by activating the PPAR-γ signaling pathway through alleviating the constraint imposed by ImP.}, }
@article {pmid40044736, year = {2025}, author = {Song, Y and Li, N and Jiang, S and Wang, K and Lv, G and Fan, Z and Du, X and Gao, W and Lei, L and Wang, Z and Liu, G and Li, X}, title = {Microbiota-derived H2S induces c-kit[+] cDC1 autophagic cell death and liver inflammation in metabolic dysfunction-associated steatohepatitis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2222}, pmid = {40044736}, issn = {2041-1723}, support = {U24A20454//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32473104//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Liver/pathology/metabolism ; Humans ; *Autophagy ; Male ; *Proto-Oncogene Proteins c-kit/metabolism/genetics ; *Hydrogen Sulfide/metabolism ; *Fatty Liver/metabolism/pathology/microbiology ; *Mice, Inbred C57BL ; Disease Models, Animal ; Dysbiosis/microbiology/metabolism ; Mice, Knockout ; Inflammation/metabolism/pathology ; Dendritic Cells/metabolism/immunology ; Diet, Western/adverse effects ; Female ; }, abstract = {Immune dysregulation-induced inflammation serves as a driving force in the progression of metabolic dysfunction-associated steatohepatitis (MASH), while the underlying cellular and molecular mechanisms remain largely uncharted. A Western diet (WD) is employed to construct mouse models of metabolic dysfunction associated steatotic liver disease (MASLD) or MASH. Mass cytometry identifies a c-kit[+] cDC1 subset whose frequency is reduced in the livers of mice and patients with MASH compared with healthy controls. Adoptive cell transfer of c-kit[+] cDC1 protects the progression of MASH. Moreover, analysis of gut microbe sequence shows that WD-fed mice and MASLD/MASH patients exhibit gut microbiota dysbiosis, with an elevated abundance of H2S-producing Desulfovibrio_sp. Transplanting of MASH-derived fecal flora, Desulfovibrio_sp., or injecting H2S intraperitoneally into MASLD mice decreases the c-kit[+]cDC1 population and exacerbates liver inflammation. Mechanistically, H2S induces autophagic cell death of cDC1 in a c-kit-dependent manner in cDC-specific c-kit[-/-] and Atg5[-/-] mice. We thus uncover that microbiota-derived H2S triggers the autophagic cell death of c-kit[+] cDC1 and ignites the liver inflammatory cascade in MASH.}, }
@article {pmid40042965, year = {2025}, author = {Sun, W and Jia, J and Liu, G and Liang, S and Huang, Y and Xin, M and Chang, Z and Liu, X and Ma, C and Song, X and He, F and Song, Y and Wu, M}, title = {Polysaccharides Extracted from Old Stalks of Asparagus officinalis L. Improve Nonalcoholic Fatty Liver by Increasing the Gut Butyric Acid Content and Improving Gut Barrier Function.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {11}, pages = {6632-6645}, doi = {10.1021/acs.jafc.4c07078}, pmid = {40042965}, issn = {1520-5118}, mesh = {Animals ; *Non-alcoholic Fatty Liver Disease/metabolism/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Polysaccharides/chemistry/pharmacology/administration &amp; dosage ; Male ; *Mice, Inbred C57BL ; Humans ; *Butyric Acid/metabolism ; *Asparagus Plant/chemistry ; Bacteria/classification/isolation &amp; purification/drug effects/genetics ; Plant Extracts/administration &amp; dosage/chemistry ; NF-kappa B/metabolism/genetics ; Liver/metabolism/drug effects ; Toll-Like Receptor 4/metabolism/genetics ; Signal Transduction/drug effects ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) ranks among the most prevalent chronic liver diseases worldwide, yet effective treatments remain scarce. Old stalks of Asparagus officinalis L. are rich in polysaccharides. The anti-NAFLD mechanism of polysaccharides from old stalks of A. officinalis (AP) requires further study. Here, we studied the effects of AP on NAFLD mice and its impact on the gut microbiota. AP intervention reduces blood lipids and liver lipids and reduces liver injury and inflammation in mice with NAFLD. Moreover, AP intervention changed gut microbiota composition and increased the abundances of butyric acid-producing bacteria, thereby increasing plasma concentration of butyric acid. Furthermore, AP intervention regulated the AMPK/SREBPs signaling pathway, thereby affecting hepatic lipid synthesis. Additionally, AP intervention improved gut barrier function and reduced plasma LPS levels, which subsequently inhibited the LPS/TLR4/NF-κB signaling pathway, thereby alleviating inflammation in NAFLD model mice. Importantly, fecal microbiota transplant (FMT) outcomes demonstrated that AP-induced changes in the gut microbiota impact the AMPK/SREBPs and LPS/TLR4/NF-κB pathways. These data suggest that AP intervention ameliorates NAFLD by regulating the gut microbiota. These research provides a scientific foundation for the use of the stalks of A. officinalis in the treatment of NAFLD.}, }
@article {pmid40041456, year = {2025}, author = {Farah, A and Paul, P and Khan, AS and Sarkar, A and Laws, S and Chaari, A}, title = {Targeting gut microbiota dysbiosis in inflammatory bowel disease: a systematic review of current evidence.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1435030}, pmid = {40041456}, issn = {2296-858X}, abstract = {INTRODUCTION: The dysbiosis of the gut microbiota has been identified as a central factor in the pathogenesis of inflammatory bowel disease (IBD), a chronic condition characterized by frequent recurrence and various adverse effects of traditional therapies. While treatments targeting the gut microbiota show promise, their efficacy in IBD management still requires extensive evaluation. Our systematic review analyzes recent studies to elucidate the advancements and challenges in treating IBD using microbial-based therapies.<br><br>METHODS: Through a comprehensive systematic review spanning key scientific databases-PubMed, Embase, Cochrane, Web of Science, Scopus, and Google Scholar-we scrutinized the impact of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on individuals with IBD. Our detailed analysis covered study and participant demographics, along with seven key outcome measures: disease activity index, inflammatory markers, serum cytokines, microbiome composition, adverse effects, and the rates of remission and relapse.<br><br>RESULTS: From 6,080 initial search hits, we included 71 studies that assessed various interventions compared to placebo or standard medical therapy. Although there was notable variation in clinical results while assessing different outcomes, overall, probiotics, prebiotics, and synbiotics enhanced the success rates in inducing remission among IBD patients. Furthermore, we noted significant reductions in levels of pro-inflammatory markers and cytokines. Additionally, the requirement for steroids, hospitalization, and poor outcomes in endoscopic and histological scores were significantly reduced in individuals undergoing FMT.<br><br>CONCLUSION: Our investigation highlights the potential of targeting gut microbiota dysbiosis with microbial-based therapies in patients with IBD. We recommend conducting larger, placebo-controlled randomized trials with extended follow-up periods to thoroughly assess these treatments' clinical efficacy and safety before widespread recommendations for clinical application.}, }
@article {pmid40040709, year = {2025}, author = {Liu, X and Yang, K and Jia, Y and Yeertai, Y and Wu, C and Wang, X and Jia, Q and Gu, Z and Cong, J and Ling, J}, title = {Chaihushugan powder regulates the gut microbiota to alleviate mitochondrial oxidative stress in the gastric tissues of rats with functional dyspepsia.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1549554}, pmid = {40040709}, issn = {1664-3224}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dyspepsia/drug therapy/metabolism/therapy ; *Oxidative Stress/drug effects ; Rats ; Male ; *Mitochondria/metabolism/drug effects ; Rats, Sprague-Dawley ; Disease Models, Animal ; Powders ; Gastric Mucosa/metabolism/microbiology/drug effects ; Fecal Microbiota Transplantation ; Drugs, Chinese Herbal/pharmacology/therapeutic use ; Gastrointestinal Motility/drug effects ; Antioxidants/pharmacology ; }, abstract = {INTRODUCTION: Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder associated with oxidative stress (OS) and dysbiosis. Chaihushugan powder (CHSGP) demonstrates efficacy in treating FD; however, the underlying therapeutic mechanism is not yet elucidated. This study aims to investigate the effects of CHSGP on OS and gut microbiota (GM) in FD rats, with a particular emphasis on the role of GM as a potential target for the antioxidant properties of CHSGP.<br><br>METHODS: The FD rat model was established with a modified tail-clamp stimulation and the administration of the CHSGP decoction at a dosage of 9.6 g/kg via gavage for a duration of 4 weeks. The GM was depleted by the administration of a cocktail of metronidazole (200 mg/kg), ampicillin (200 mg/kg), neomycin sulfate (200 mg/kg), and vancomycin (100 mg/kg). Fecal microbiota transplantation (FMT) was performed with CHSGP-treated fecal supernatant at a dosage of 10 mL/kg. The gastrointestinal motility was measured using the rates of gastric emptying and small intestine propulsion. Hematoxylin and eosin staining was employed to elucidate the pathological changes, while the transmission electron microscope was used to examine the microstructures of the interstitial cells of Cajal (ICC). Chemiluminescence, colorimetric assay, immunofluorescence co-staining, and western blot assay were employed to identify the OS-related markers (ROS, SOD, NOX4, PRDX1, and TRX2). Sequencing of fecal microbiota was performed utilizing 16S rDNA.<br><br>RESULTS: The CHSGP decoction promoted gastrointestinal motility, protected the microstructure of ICC, and reduced OS in FD rats. The GM composition was also regulated by CHSGP. However, these effects disappeared after microbiota depletion. Fortunately, the FMT therapy reinstated them.<br><br>CONCLUSION: Chaihushugan powder decoction might regulate the GM to alleviate mitochondrial OS in the gastric tissues of FD rats.}, }
@article {pmid40040609, year = {2025}, author = {Liu, FQ and An, ZY and Cui, LJ and Xiao, MY and Wu, YJ and Li, W and Zhang, BS and Yu, L and Feng, J and Liu, ZG and Feng, R and Jiang, ZX and Huang, RB and Jing, HM and Ren, JH and Zhu, XY and Cheng, YF and Li, YH and Zhou, HB and Gao, D and Liu, Y and Yu, F and Wang, X and Qiao, JL and Hu, DH and Wang, LL and Zang, MT and Chen, Q and Qu, QY and Zhou, JY and Li, ML and Chen, YX and Huang, QS and Fu, HX and Li, YY and Wang, QF and Huang, XJ and Zhang, XH and , }, title = {Correlation Between Fecal Microbiota and Corticosteroid Responsiveness in Primary Immune Thrombocytopenia: an Exploratory Study.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2410417}, doi = {10.1002/advs.202410417}, pmid = {40040609}, issn = {2198-3844}, support = {2023YFC2507803//Key Technologies Research and Development Program/ ; 82300149//National Natural Science Foundation of China/ ; 82130008//National Natural Science Foundation of China/ ; 82230004//National Natural Science Foundation of China/ ; 82350004//National Natural Science Foundation of China/ ; 82430006//National Natural Science Foundation of China/ ; 2024M761208//China Postdoctoral Science Foundation/ ; 2023ZB182//Department of Human Resources and Social Security of Jiangsu Province/ ; 2022-1-4082//Capital Health Research and Development of Special Fund/ ; 7242154//Natural Science Foundation of Beijing Municipality/ ; 7232188//Natural Science Foundation of Beijing Municipality/ ; 71003Y3035//Peking University Medicine/ ; }, abstract = {Corticosteroids (CSs) are the initial therapy for immune thrombocytopenia (ITP); however, their efficacy is not adequately predicted. As a novel biomarker, the composition of the gut microbiota is non-invasively tested and altered in patients with ITP. This study aims to develop a predictive model that leverages gut microbiome data to predict the CS response in patients with ITP within the initial four weeks of treatment. Metagenomic sequencing is performed on fecal samples from 212 patients with ITP, 152 of whom underwent CS treatment and follow-up. Predictive models are trained using six machine-learning algorithms, integrating clinical indices and gut microbiome data. The support vector machine (SVM) algorithm-based model has the highest accuracy (AUC = 0.80). This model utilized a comprehensive feature set that combined clinical data (including sex, age, duration, platelet count, and bleeding scales) with selected microbial species (including Bacteroides ovatus, Bacteroides xylanisolvens, and Parabacteroides gordonii), alpha diversities, KEGG pathways, and microbial modules. This study will provide new ideas for the prediction of clinical CS efficacy, enabling informed decision-making regarding the initiation of CS or personalized treatment in patients with ITP.}, }
@article {pmid40038211, year = {2025}, author = {Malik, S and Naqvi, SAA and Shadali, AH and Khan, H and Christof, M and Niu, C and Schwartz, DA and Adler, DG}, title = {Fecal Microbiota Transplantation (FMT) and Clinical Outcomes Among Inflammatory Bowel Disease (IBD) Patients: An Umbrella Review.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {40038211}, issn = {1573-2568}, abstract = {BACKGROUND AND AIMS: Recent systematic reviews and meta-analyses (SRMAs) have shown inconsistent effectiveness of FMT among patients with IBD. This study aimed to appraise the evidence for clinically relevant outcomes with FMT in patients with IBD using published SRMAs.<br><br>METHODS: We searched major databases from inception through Nov 2023 to identify SRMAs assessing the effectiveness of FMT in patients with IBD. Primary outcomes included clinical remission, clinical response, endoscopic remission/response, a composite endpoint, and adverse effects. We included SRMAs investigating FMT's effect in patients with IBD using RCTs and observational studies data. Methodological quality and evidence certainty were assessed using AMSTAR 2 and GRADE.<br><br>RESULTS: Out of 106 citations, 16 SRMAs were included with varying study sizes (2 to 60 primary studies) and participants (112 to 1169 per SRMA). Five SRMAs assessed FMT in IBD, while 11 focused on Ulcerative Colitis (UC). Seven SRMAs included RCTs only, and nine included both RCTs and observational studies. Methodological quality was critically low in 9 SRMAs (56%) and low in 7 studies (44%). FMT showed clinical remission benefit in all 16 SRMAs, with varying certainty: 3 high, 4 moderate, 4 low, and 5 very low. Endoscopic remission/response was reported in 5 meta-analyses on UC, with 1 high, 3 moderate, and 1 very low certainty. Combined clinical remission and endoscopic response were reported in 3 SRMAs on UC, with 1 low and 2 moderate certainty. Adverse events were reported in 6 SRMAs, with 1 high, 3 moderate, 1 low, and 1 very low certainty.<br><br>CONCLUSION: Current evidence shows potential benefits of FMT in IBD, particularly UC, supported by significant associations in 16 meta-analyses. However, poor methodological quality and variability in evidence certainty call for high-quality RCTs to strengthen the evidence.}, }
@article {pmid40037667, year = {2025}, author = {Wei, Y and Qin, L and Wu, X and Li, D and Qian, D and Jiang, H and Geng, Q}, title = {Faecal microbiota transplantation combined with platinum-based doublet chemotherapy and tislelizumab as first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC): study protocol for a prospective, multicentre, single-arm exploratory trial.}, journal = {BMJ open}, volume = {15}, number = {3}, pages = {e094366}, pmid = {40037667}, issn = {2044-6055}, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/therapy/drug therapy ; *Lung Neoplasms/therapy/drug therapy ; *Fecal Microbiota Transplantation/methods ; Prospective Studies ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Adult ; Female ; Multicenter Studies as Topic ; Male ; Middle Aged ; Combined Modality Therapy ; Aged ; }, abstract = {INTRODUCTION: The standard first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC) is chemotherapy combined with immunotherapy. However, owing to the immune microenvironment imbalance and immune status impairment caused by repeated chemotherapy, as well as the primary or secondary resistance to immune checkpoint inhibitors, the efficacy of immunotherapy combined with chemotherapy remains unsatisfactory. Recent studies have shown that faecal microbiota transplantation (FMT) can modulate the intestinal microflora, influence the tumour immune microenvironment and even enhance the efficacy of immunotherapy. Hence, we conduct such a prospective, exploratory study to evaluate the efficacy and safety of integrating FMT with standard first-line treatment in patients with driver-gene negative advanced NSCLC.<br><br>METHODS AND ANALYSIS: FMT-JSNO-02 (NCT06403111) is a prospective, multicentre, single-arm exploratory study. It is planned to include 62 cases of previously untreated driver-gene negative, Eastern Cooperative Oncology Group Performance Status 0-1, programmed death ligand 1<50% advanced NSCLC patients, who will be given FMT by orally ingested stool capsules on the basis of standard first-line treatment of chemotherapy combined with immunotherapy. The primary endpoint of this study is the 12-month progression-free survival rate.<br><br>ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the Second People's Hospital of Changzhou (number [2024] YLJSA005) and is being conducted in accordance with the principles of the Declaration of Helsinki. The results of this study will be disseminated through publication in a peer-reviewed journal and presentation at scientific conferences.<br><br>TRIAL REGISTRATION NUMBER: NCT06403111. Date of registration: 7 May 2024, the first version protocol.}, }
@article {pmid40037430, year = {2025}, author = {Gao, J and He, Y and Shi, F and Hou, F and Wu, X and Yi, Y and Zhang, Y and Gong, Q}, title = {Activation of Sirt6 by icariside Ⅱ alleviates depressive behaviors in mice with poststroke depression by modulating microbiota-gut-brain axis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.03.002}, pmid = {40037430}, issn = {2090-1224}, abstract = {BACKGROUND: Sirt6-mediated gut microbiota plays a vital role in poststroke depression (PSD). Icariside Ⅱ (ICS Ⅱ) is a naturally-occurring neuroprotectant with Sirt6 induction potency. However, it is unknown whether ICS Ⅱ protects against PSD through modulation of gut microbiota.<br><br>OBJECTIVE: This study aimed to reveal the effect and potential mechanisms of ICS &#x2161; on PSD, and the role of the microbiota-gut-brain axis was investigated.<br><br>METHODS: Using middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS) to establish post-stroke depression (PSD) mice, we assessed anti-depressant effects of ICS &#x2161; via behavioral tests, immunohistochemistry, and western blot. Transcriptome profiling, molecular docking, and surface plasmon resonance were used to identify key targets. 16S rDNA genomic-derived taxonomic profiling and fecal microbiota transplantation (FMT) were conducted to figure out the mechanistic role of the gut microbiota and short-chain fatty acids (SCFAs).<br><br>RESULTS: ICS &#x2161; ameliorated depressive-like behaviors in PSD mice as evidenced by sucrose preference test, forced swimming test and tail suspension test. ICS &#x2161; restored mitochondrial function, reduced oxidative damage and pro-inflammatory cytokines both in brain and intestine through regulation of Sirt6/NF-&#x3ba;B pathway. ICS &#x2161; significantly increased the abundance of gut microbiota (such asAkkermansia and Ligilactobacillus), enhanced SCFAs concentrations, repaired intestinal barrier integrity and upreglated the tight junction protein expression. FMT from ICS II-treated mice replicated these benefits, confirming gut microbiota's role. Mechanistically, ICS &#x2161; directly bound to Sirt6 and enhanced its activity. However, ICS &#x2161;-mediated neuroprotection was neutralized in PSD mice or hydrogen peroxide-induced enteric glial cells when Sirt6 was absent.<br><br>CONCLUSION: Our findings expand the pharmacological properties of ICS II by demonstrating its ability to ameliorate PSD through modulation of the microbiota-gut-brain axis. ICS &#x2161;, as a novel Sirt6 activator, could be translated into an alternative microbiota-targeted avenue for coping with PSD.}, }
@article {pmid40037353, year = {2025}, author = {Tian, S and Kim, MS and Zhao, J and Heber, K and Hao, F and Koslicki, D and Tian, S and Singh, V and Patterson, AD and Bisanz, JE}, title = {A designed synthetic microbiota provides insight to community function in Clostridioides difficile resistance.}, journal = {Cell host &amp; microbe}, volume = {33}, number = {3}, pages = {373-387.e9}, pmid = {40037353}, issn = {1934-6069}, support = {R00 AI147165/AI/NIAID NIH HHS/United States ; R35 GM151045/GM/NIGMS NIH HHS/United States ; }, mesh = {*Clostridioides difficile/physiology ; Animals ; Humans ; Mice ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Clostridium Infections/microbiology ; Feces/microbiology ; Germ-Free Life ; Anti-Bacterial Agents/pharmacology ; Disease Models, Animal ; Diarrhea/microbiology ; Drug Resistance, Bacterial ; Bile Acids and Salts/metabolism ; Fermentation ; }, abstract = {Clostridioides difficile, a major cause of antibiotic-associated diarrhea, is suppressed by the gut microbiome, but the precise mechanisms are not fully described. Through a meta-analysis of 12 human studies, we designed a synthetic fecal microbiota transplant (sFMT1) by reconstructing microbial networks negatively associated with C. difficile colonization. This lab-built 37-strain consortium formed a functional community suppressing C. difficile in vitro and in animal models. Using sFMT1 as a tractable model system, we find that bile acid 7α-dehydroxylation is not a determinant of sFMT1 efficacy while one strain performing Stickland fermentation-a pathway of competitive nutrient utilization-is both necessary and sufficient for the suppression of C. difficile, replicating the efficacy of a human fecal transplant in a gnotobiotic mouse model. Our data illustrate the significance of nutrient competition in suppression of C. difficile and a generalizable approach to interrogating complex community function through robust methods to leverage publicly available sequencing data.}, }
@article {pmid40036939, year = {2025}, author = {Mallick, K and Khodve, G and Ruwatia, R and Banerjee, S}, title = {Gut microbes: Therapeutic Target for neuropsychiatric disorders.}, journal = {Journal of psychiatric research}, volume = {184}, number = {}, pages = {27-38}, doi = {10.1016/j.jpsychires.2025.02.031}, pmid = {40036939}, issn = {1879-1379}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy/microbiology ; *Mental Disorders/microbiology/therapy ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Animals ; Prebiotics ; }, abstract = {Neuropsychiatric diseases encompass a range of mental and neurological disorders that have a significant and far-reaching effect on an individual's quality of life. These conditions affect not only the mental status but also the physical well-being of individuals, which leads to weakened immune systems and other diseases. Emerging research underscores a significant connection between the gut microbiome and neuropsychiatric diseases, suggesting that microbial communities within the gastrointestinal tract may influence brain function and mental health. Gut dysbiosis is caused by various factors, including stress, diet, inappropriate usage of antibiotics, infections, and so on, all of which can disrupt numerous pathways, resulting in abnormal neurotransmitter signaling, inflammation, and impaired brain function. Similarly, various neuropsychiatric diseases can disrupt the specific microbiome in the gut, leading to gut dysbiosis, often impairing memory and cognitive function. The growing evidence supporting the role of gut dysbiosis in neuropsychiatric disorders has opened up new avenues for therapeutic interventions. Modulating the gut microbiome through strategies such as probiotics, prebiotics, or fecal microbiota transplantation has shown promising results in various studies of neuropsychiatric disorders. However, further research is needed to fully elucidate the mechanisms involved in gut dysbiosis-associated brain changes to develop effective and personalized treatment strategies for neuropsychiatric diseases.}, }
@article {pmid40035163, year = {2025}, author = {Longhitano, A and Roder, C and Blackmore, T and Campbell, A and May, M and Athan, E}, title = {Australasian Society of Infectious Diseases updated guidelines for the management of Clostridioides difficile infection in adults and children in Australia and New Zealand.}, journal = {Internal medicine journal}, volume = {55}, number = {3}, pages = {503-513}, doi = {10.1111/imj.16638}, pmid = {40035163}, issn = {1445-5994}, mesh = {Humans ; Australia ; *Clostridium Infections/therapy/epidemiology ; New Zealand/epidemiology ; *Anti-Bacterial Agents/therapeutic use ; Adult ; Child ; *Clostridioides difficile ; Vancomycin/therapeutic use ; Metronidazole/therapeutic use ; Fecal Microbiota Transplantation ; Fidaxomicin/therapeutic use ; Societies, Medical ; Practice Guidelines as Topic ; }, abstract = {Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality within the Australian population. Treatment recommendations for CDI pose challenges at both community and hospital-based levels due to the recurrent, refractory and potentially severe nature of the disease. Since the last published Australasian guidelines in 2016, new therapeutic options are available, prompting a necessary update to management recommendations. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children exploring the changes to treatment recommendations - including the replacement of oral metronidazole with vancomycin for initial CDI and the emerging role for fidaxomicin and faecal-microbiota transplant.}, }
@article {pmid40033229, year = {2025}, author = {Sóti, &#xc1; and Nagy, G and Győri, Z and Vass, T and Hetzman, L and Fenyves, BG and Varga, C}, title = {Tension pneumothorax from large bowel herniation and perforation as a late presentation of traumatic diaphragmatic hernia during pregnancy: a case report.}, journal = {International journal of emergency medicine}, volume = {18}, number = {1}, pages = {40}, pmid = {40033229}, issn = {1865-1372}, abstract = {BACKGROUND: Diaphragmatic hernias can be congenital or acquired, with trauma being the primary cause of the latter. Both types may have delayed presentations, with abdominal organs protruding into the thoracic cavity, causing symptoms of varying severity. Pregnancy can sometimes precipitate the condition. Tension pneumothorax resulting from bowel perforation into the thorax is exceptionally rare, with only a few cases reported. To the best of the authors knowledge, this is the third documented case of a late-presenting trauma-related diaphragmatic hernia during pregnancy, complicated by tension pneumothorax.<br><br>CASE PRESENTATION: A 30-year-old woman, 29 weeks pregnant, was referred to Semmelweis University emergency department with moderate dyspnea. Initial investigation revealed tension pneumothorax. Chest tube placement released air, pus, and feces. Computer tomography identified a diaphragmatic hernia with bowel incarceration and perforation as the underlying cause. The patient underwent a delayed cesarean section and surgical repair, with a good outcome. A history of thoracic trauma eight years prior was later revealed.<br><br>CONCLUSION: Evaluating pregnant patients with shortness of breath in the emergency department is challenging. Identifying a history of thoracic or abdominal trauma is crucial, as this can raise the suspicion of diaphragmatic hernia, which can present with a wide range of symptoms. Spontaneous tension pneumothorax in pregnant women is extremely rare and requires cautious management. A multidisciplinary approach is crucial for the successful treatment of maternal diaphragmatic hernia.}, }
@article {pmid40027572, year = {2025}, author = {Zhang, JG and Wang, YW and Wang, QY and Wen, B}, title = {Clinical features and risk factors for combined Klebsiella pneumoniae infection in patients with liver cirrhosis.}, journal = {World journal of hepatology}, volume = {17}, number = {2}, pages = {103648}, pmid = {40027572}, issn = {1948-5182}, abstract = {This article discusses the findings presented by Zhang et al. They analyzed the risk factors and clinical characteristics associated with Klebsiella pneumoniae infection in patients with liver cirrhosis treated at a hospital in Beijing. In this article, we focus on the connection between chronic kidney disease and the intestinal microbiota, and propose microbiota transplantation as a potential treatment for this patient group. We also examine an intriguing phenomenon related to hepatic encephalopathy, and provide insights into the future research.}, }
@article {pmid40027490, year = {2025}, author = {Xie, C and Cheng, J and Chen, P and Yan, X and Luo, C and Qu, H and Shu, D and Ji, J}, title = {Integrating gut and IgA-coated microbiota to identify Blautia as a probiotic for enhancing feed efficiency in chickens.}, journal = {iMeta}, volume = {4}, number = {1}, pages = {e264}, pmid = {40027490}, issn = {2770-596X}, abstract = {This study explores the role of IgA-coated bacteria in improving feed efficiency in chickens, offering a novel perspective for probiotic screening. Chickens with high feed efficiency were found to have a greater abundance of Gram-positive bacteria, while low feed efficiency chickens exhibited higher levels of Gram-negative bacteria and potential pathogens. Through fecal microbiota transplantation (FMT) and integrating analysis of cecal and IgA-coated microbiota, we precisely identified Blautia as a key genus linked to improved feed efficiency. Further validation demonstrated that Blautia coccoides, a representative species of this genus, enhances feed efficiency and activates B cells to produce Immunoglobulin A (IgA), both in vivo and in vitro. Our findings provide new insights into the potential of IgA-coated bacteria as functional probiotics, offering a promising strategy for enhancing feed efficiency in animal production.}, }
@article {pmid40027485, year = {2025}, author = {Liu, Y and Li, H and Sun, T and Sun, G and Jiang, B and Liu, M and Wang, Q and Li, T and Cao, J and Zhao, L and Xiao, F and Zhao, F and Cui, H}, title = {Gut microbiome and metabolome characteristics of patients with cholesterol gallstones suggest the preventive potential of prebiotics.}, journal = {iMeta}, volume = {4}, number = {1}, pages = {e70000}, pmid = {40027485}, issn = {2770-596X}, abstract = {Cholesterol gallstones (CGS) still lack effective noninvasive treatment. The etiology of experimentally proven cholesterol stones remains underexplored. This cross-sectional study aims to comprehensively evaluate potential biomarkers in patients with gallstones and assess the effects of microbiome-targeted interventions in mice. Microbiome taxonomic profiling was conducted on 191 samples via V3-V4 16S rRNA sequencing. Next, 60 samples (30 age- and sex-matched CGS patients and 30 controls) were selected for metagenomic sequencing and fecal metabolite profiling via liquid chromatography-mass spectrometry. Microbiome and metabolite characterizations were performed to identify potential biomarkers for CGS. Eight-week-old male C57BL/6J mice were given a lithogenic diet for 8 weeks to promote gallstone development. The causal relationship was examined through monocolonization in antibiotics-treated mice. The effects of short-chain fatty acids such as sodium butyrate, sodium acetate (NaA), sodium propionate, and fructooligosaccharides (FOS) on lithogenic diet-induced gallstones were investigated in mice. Gut microbiota and metabolites exhibited distinct characteristics, and selected biomarkers demonstrated good diagnostic performance in distinguishing CGS patients from healthy controls. Multi-omics data indicated associations between CGS and pathways involving butanoate and propanoate metabolism, fatty acid biosynthesis and degradation pathways, taurine and hypotaurine metabolism, and glyoxylate and dicarboxylate metabolism. The incidence of gallstones was significantly higher in the Clostridium glycyrrhizinilyticum group compared to the control group in mice. The grade of experimental gallstones in control mice was significantly higher than in mice treated with NaA and FOS. FOS could completely inhibit the formation of gallstones in mice. This study characterized gut microbiome and metabolome alterations in CGS. C. glycyrrhizinilyticum contributed to gallstone formation in mice. Supplementing with FOS could serve as a potential approach for managing CGS by altering the composition and functionality of gut microbiota.}, }
@article {pmid40027479, year = {2025}, author = {Shi, Y and Chen, Z and Fang, T and Chen, X and Deng, Y and Qin, H and Lian, M and Shen, J and Zong, Y and Chu, H and Hoebinger, C and Guo, H and Yuan, Z and Zheng, J and Zhou, Y and Pan, Y and Mendes, BG and Lang, S and Hendrikx, T and Zeng, S and Cao, H and Yang, L and Chen, L and Chen, P and Dai, L and Wang, H and Yin, S and Zhu, S and Ma, X and Schnabl, B and Chen, H and Duan, Y}, title = {Gut microbiota in treating inflammatory digestive diseases: Current challenges and therapeutic opportunities.}, journal = {iMeta}, volume = {4}, number = {1}, pages = {e265}, pmid = {40027479}, issn = {2770-596X}, support = {P30 DK120515/DK/NIDDK NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; }, abstract = {Accumulating evidence indicates that the gut microbiota is intricately involved in the initiation and progression of human diseases, forming a multidirectional regulatory axis centered on intestinal microbiota. This article illustrates the challenges in exploring the role of the gut microbiota in inflammatory digestive diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD) and inflammatory bowel disease (IBD), and summarizes the existing microbiome-focused treatment strategies (probiotics, prebiotics, symbiotics, fecal microbiota transplantation, and bacteriophages therapy), emerging technologies (gut microbiome-on-a-chip and artificial intelligence), as well as possible future research directions. Taken together, these therapeutic strategies and technologies present both opportunities and challenges, which require researchers and clinicians to test the rationality and feasibility of various therapeutic modalities in continuous practice.}, }
@article {pmid40026419, year = {2025}, author = {Marizzoni, M and Tournier, BB and Chevalier, C and Saleri, S and Lathuilière, A and Ceyzériat, K and Paquis, A and Park, R and Troesch, E and Cattaneo, A and Millet, P and Frisoni, GB}, title = {Stools from a human APOEe2 donor reduces amyloid and tau pathology and increases neuroinflammation in a 3xTg AD mouse model.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1539067}, pmid = {40026419}, issn = {1663-4365}, abstract = {BACKGROUND: The mechanisms underlying the protective effect of the e2 variant of the APOE gene (APOEe2) against Alzheimer's disease (AD) have not been elucidated. We altered the microbiota of 3xTgAD mice by fecal microbiota transplantation from a human APOEe2 donor (e2-FMT) and tested the effect of microbiota perturbations on brain AD pathology.<br><br>METHODS: FMT of bacteria isolated from stools of untreated 3xTgAD mice (M-FMT) or e2-FMT were transplanted in 15-month-old 3xTgAD mice. FMT was done alone or in combination with antibiotic and proton-pump inhibitor following the Microbiota Transfer Therapy protocol (MTT). The effect of donor (M or e2) and transplantation protocol (FMT or MTT) on hippocampal amyloid, tau pathology and neuroinflammation were assessed at the end of the treatment.<br><br>RESULTS: e2-FMT reduced amyloid, and tau pathology as well as increased neuroinflammation as compared with M-FMT. MTT was associated with reduced number of A&#x3b2;40+ plaques and tau pathology. Low levels of amyloid were associated with high levels of pro-inflammatory molecules in e2-FMT mice. These associations were partially attenuated by MTT.<br><br>CONCLUSION: Bacteria from a human APOEe2 donor reduced AD pathology and increased neuroinflammation in mice suggesting that the gut microbiota may be a mediator of the protective effect of APOEe2.}, }
@article {pmid40025650, year = {2025}, author = {Qi, C and Li, Z and Tu, H and Sun, F and Guo, W and Di, C and He, R and Ze, X and Zhang, L and Gao, R and Hu, P and Yang, W and Li, K and Liu, J and Pan, X and Jin, Z and Sun, J}, title = {2'-FL and cross-feeding bifidobacteria reshaped the gut microbiota of infants with atopic dermatitis ex vivo and prevented dermatitis in mice post-microbiota transplantation through retinol metabolism activation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2474148}, pmid = {40025650}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; Humans ; *Dermatitis, Atopic/microbiology/therapy/metabolism ; *Bifidobacterium/metabolism ; Infant ; *Trisaccharides/metabolism ; *Vitamin A/metabolism ; *Fatty Acids, Volatile/metabolism ; Milk, Human/metabolism ; Fecal Microbiota Transplantation ; Probiotics/administration &amp; dosage ; Female ; Male ; Bifidobacterium bifidum/physiology/metabolism ; Mice, Inbred BALB C ; }, abstract = {2'-Fucosyllactose (2'-FL), a predominant human milk oligosaccharide, plays a crucial role in the development of the infant gut microbiota and immune system. However, the microbiota of infants with atopic dermatitis (AD) often has difficulty utilizing 2'-FL. Here, we found that strains from human milk, Bifidobacterium bifidum FN120 and Bifidobacterium longum subsp. longum FN103, utilized 2'-FL for growth by cross-feeding. Through an ex vivo continuous fermentation system, we found that 2'-FL and cross-feeding bifidobacteria synergistically enhanced the production of short-chain fatty acids (SCFAs), particularly acetate and propionate, while reshaping the gut microbiota in infants with AD. The reshaped microbiota was then transplanted into oxazolone-induced mice. We observed that AD symptoms in mice were effectively prevented, with significant changes in the ileum microbiota and increased intestinal SCFA levels. RNA sequencing analysis of Peyer's patches in the small intestine revealed activation of the retinol metabolic pathway. Nontargeted metabolomics analysis revealed a significant increase in plasma retinoate levels, which correlated markedly with AD-related markers. Collectively, our study demonstrated that supplementation with cross-feeding bifidobacteria and 2'-FL reshaped the gut microbiota, activated retinol metabolic pathways, promoted immune tolerance, and thereby prevented AD. Our findings provide novel insights into the therapeutic potential of combining prebiotics and probiotics to modulate the gut - skin axis and support immune tolerance in early life, offering a promising strategy for infantile AD management and prevention.}, }
@article {pmid40025585, year = {2025}, author = {Guo, H and Jiang, H and Liu, H}, title = {Case report of clostridium difficile infection after rectal resection with ileostomy.}, journal = {World journal of surgical oncology}, volume = {23}, number = {1}, pages = {70}, pmid = {40025585}, issn = {1477-7819}, mesh = {Humans ; *Ileostomy/adverse effects ; *Clostridioides difficile/isolation &amp; purification ; *Rectal Neoplasms/surgery/pathology ; *Clostridium Infections/etiology/diagnosis/microbiology/therapy ; *Postoperative Complications/microbiology/diagnosis/etiology ; Male ; Prognosis ; Fecal Microbiota Transplantation/adverse effects ; Proctectomy/adverse effects ; Aged ; Middle Aged ; }, abstract = {Colorectal cancer is the third most common cancer worldwide, with high incidence and mortality rates. Surgical resection is the primary treatment for rectal cancer. To reduce the occurrence and severity of postoperative complications such as anastomotic leakage, prophylactic ileostomy is often performed concurrently. However, following ileostomy creation, there is a disruption in intestinal ecology, making patients susceptible to clostridium difficile infection. clostridium difficile is a Gram-positive anaerobic spore-forming bacterium that is resistant to most antibiotics due to spore formation, leading to high recurrence rates and treatment failure. Additionally, in the early stages of clostridium difficile infection, increased ileostomy output can be challenging to differentiate from normal postoperative conditions, potentially resulting in missed diagnosis, delayed treatment, and increased healthcare burden.This case report describes a case of high out-put ileostomy caused by clostridium difficile infection following rectal resection with ileostomy, which was successfully treated by fecal microbiota transplantation, providing evidence-based medicine for clinical practice.}, }
@article {pmid40024791, year = {2025}, author = {Kushima, H and Ishii, H}, title = {Cryptococcosis.}, journal = {Medical mycology journal}, volume = {66}, number = {1}, pages = {27-31}, doi = {10.3314/mmj.25.001}, pmid = {40024791}, issn = {2186-165X}, mesh = {Humans ; *Cryptococcosis/immunology/drug therapy/diagnosis ; *Cryptococcus neoformans/isolation &amp; purification/immunology/pathogenicity ; *Immunocompromised Host ; Animals ; Antifungal Agents/therapeutic use ; Organ Transplantation/adverse effects ; }, abstract = {Approximately one million new cases of cryptococcosis develop each year worldwide, resulting in approximately 600,000 deaths. Most cases occurred in HIV patients from African countries south of the Sahara Desert. In light of this situation, in 2022, the World Health Organization presented a list of priority fungal pathogens to guide research, development, and public health action, with Cryptococcus neoformans as the most important critical fungus. In contrast, a recent retrospective study in developed countries showed that 90% of cases with cryptococcosis were non-HIV patients, including immunocompetent individuals. Underlying diseases of non-HIV immunocompromised patients include cancer and solid organ transplantation. High serum titers cryptococcal antigens independently predicted the risk of central nervous system involvement. Even if the patient is asymptomatic, high antigen levels are considered a possibility of cryptococcal meningitis, and a spinal fluid examination may be recommended. The absence of a history of contact with pigeons should not be used as a basis for denying cryptococcosis because C. neoformans is often detected in old and dried feces of chickens other than pigeons. Donor-derived cryptococcosis is a unique feature of cryptococcosis in solid organ transplant recipients. Pre-transplant screening tests for cryptococcosis, pre-transplant treatment for the donor, and prophylactic antifungal therapy for the recipient may be useful. Defense against cryptococcal infection is regulated by various mechanisms, including Th1, Th2, and Th17 immune responses. Molecularly targeted medicines that target specific cytokines or surface antigen molecules have been widely used with excellent clinical efficacy for the treatment of various diseases. Since cryptococcosis has been recently reported to develop during the use of certain medicines, such as ibrutinib and eculizumab, clinicians need to be mindful that the number of similar cases may increase in the future.}, }
@article {pmid40024538, year = {2025}, author = {Sliti, A and Kim, RH and Lee, D and Shin, JH}, title = {Whole genome sequencing and In silico analysis of the safety and probiotic features of Lacticaseibacillus paracasei FMT2 isolated from fecal microbiota transplantation (FMT) capsules.}, journal = {Microbial pathogenesis}, volume = {202}, number = {}, pages = {107405}, doi = {10.1016/j.micpath.2025.107405}, pmid = {40024538}, issn = {1096-1208}, mesh = {*Probiotics ; *Whole Genome Sequencing ; *Fecal Microbiota Transplantation ; *Genome, Bacterial ; *Lacticaseibacillus paracasei/genetics ; Humans ; Phylogeny ; Computer Simulation ; Prophages/genetics ; Gastrointestinal Microbiome/genetics ; Virulence Factors/genetics ; Feces/microbiology ; Capsules ; Plasmids/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats ; }, abstract = {Lacticaseibacillus paracasei is widely used as a probiotic supplement and food additive in the medicinal and food industries. However, its application requires careful evaluation of safety traits associated with probiotic pathogenesis, including the transfer of antibiotic-resistance genes, the presence of virulence and pathogenicity factors, and the potential disruptions of the gut microbiome and immune system. In this study, we conducted whole genome sequencing (WGS) of L. paracasei FMT2 isolated from fecal microbiota transplantation (FMT) capsules and performed genome annotation to assess its probiotic and safety attributes. Our comparative genomic analysis assessed this novel strain's genetic attributes and functional diversity and unraveled its evolutionary relationships with other L. paracasei strains. The assembly yielded three contigs: one corresponding to the chromosome and two corresponding to plasmids. Genome annotation revealed the presence of 2838 DNA-coding sequences (CDS), 78 ribosomal RNAs (rRNAs), 60 transfer RNAs (tRNAs), three non-coding RNAs (ncRNAs), and 126 pseudogenes. The strain lacked antibiotic resistance genes and pathogenicity factors. Two intact prophages, one Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) region, and three antimicrobial peptide gene clusters were identified, highlighting the genomic stability and antimicrobial potential of the strain. Furthermore, genes linked to probiotic functions, such as mucosal colonization, stress resistance, and biofilm formation, were characterized. The pan-genome analysis identified 3358 orthologous clusters, including 1775 single-copy clusters, across all L. paracasei strains. Notably, L. paracasei FMT2 contained many unique singleton genes, potentially contributing to its distinctive probiotic properties. Our findings confirm the potential of L. paracasei FMT2 for food and therapeutic applications based on its probiotic profile and safety.}, }
@article {pmid40024260, year = {2025}, author = {Karmisholt Grosen, A and Mikkelsen, S and Aas Hindhede, L and Ellegaard Paaske, S and Dahl Baunwall, SM and Mejlby Hansen, M and Frederik Dahlerup, J and Steen Mortensen, M and Rask Licht, T and Kjærgaard Boldsen, J and Tornvig Erikstrup, L and Lodberg Hvas, C and Erikstrup, C}, title = {Effects of clinical donor characteristics on the success of faecal microbiota transplantation for patients in Denmark with Clostridioides difficile infection: a single-centre, prospective cohort study.}, journal = {The Lancet. Microbe}, volume = {}, number = {}, pages = {101034}, doi = {10.1016/j.lanmic.2024.101034}, pmid = {40024260}, issn = {2666-5247}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for patients with recurrent Clostridioides difficile infection, but donor selection can influence its clinical success. We aimed to investigate the effect of clinical donor characteristics on FMT outcomes in patients with C difficile infection.<br><br>METHODS: In this single-centre, prospective cohort study, we included all donors who fulfilled the national criteria for faeces donation and delivered donations to the Centre for Faecal Microbiota Transplantation, Aarhus University Hospital, Denmark, between May 2, 2016, and Oct 31, 2023, and corresponding recipients treated with one-dose FMT for primary or recurrent C&#xa0;difficile infection. In mixed-effects models, we evaluated the effect of donor sex, age, BMI, smoking status, donation stool consistency, total donation weight, antibiotic use, Helicobacter pylori carriage, birth mode, donor-recipient sex concordance, and the alpha diversity of faeces donations on FMT outcomes in recipients. The primary outcome was the resolution of diarrhoea associated with C&#xa0;difficile infection in patients 8&#xa0;weeks after FMT.<br><br>FINDINGS: Among 145&#xa0;blood donors who also donated faeces, 115 (79&#xb7;3%) were men and 30 (20&#xb7;7%) were women. 90&#xa0;(62&#xb7;1%) provided faeces for 1351&#xa0;evaluable FMTs in 952&#xa0;patients with C&#xa0;difficile infection. 1037 (76&#xb7;8%) FMTs were administered through oral capsules, 151 (11&#xb7;2%) via colonoscopy, and 163&#xa0;FMTs (12&#xb7;1%) via nasojejunal tube. Antibiotic use 3-12&#xa0;months before donation decreased the effectiveness of FMT (odds ratio 0&#xb7;55 [95% CI 0&#xb7;33-0&#xb7;91]; p=0&#xb7;019). Compared with donations with a Bristol Stool Form Scale (BSFS) score of 3, donations with a score of 4&#xa0;(odds ratio&#xa0;1&#xb7;38 [95% CI 1&#xb7;04-1&#xb7;83]; p=0&#xb7;024) and 5&#xa0;or above (2&#xb7;89 [1&#xb7;33-6&#xb7;26]; p=0&#xb7;0072) showed improved FMT effectiveness. Donor sex, BMI, smoking status, H&#xa0;pylori carriage, birth mode, total donation weight, and donor-recipient sex concordance did not affect FMT outcomes.<br><br>INTERPRETATION: Expanding current donor selection criteria to avoid antibiotic use in the 12&#xa0;months preceding donation and including donations with a BSFS score of 5&#xa0;might improve FMT outcomes for patients with C&#xa0;difficile infection. Our findings call for the revision of current clinical donor screening practices, and future studies could further optimise the criteria for selecting optimal faeces donors.<br><br>FUNDING: Innovation Fund Denmark.}, }
@article {pmid40023843, year = {2025}, author = {Golomb, SM and Guldner, IH and Aleksandrovic, E and Fross, SR and Liu, X and Diao, L and Liang, K and Wu, J and Wang, Q and Lopez, JA and Zhang, S}, title = {Temporal dynamics of immune cell transcriptomics in brain metastasis progression influenced by gut microbiome dysbiosis.}, journal = {Cell reports}, volume = {44}, number = {3}, pages = {115356}, pmid = {40023843}, issn = {2211-1247}, support = {R01 CA222405/CA/NCI NIH HHS/United States ; R21 CA263798/CA/NCI NIH HHS/United States ; R01 CA194697/CA/NCI NIH HHS/United States ; R01 CA255064/CA/NCI NIH HHS/United States ; F31 CA261046/CA/NCI NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; *Dysbiosis/immunology ; Animals ; *Brain Neoplasms/immunology/genetics/microbiology/pathology ; Mice ; *Disease Progression ; Mice, Inbred C57BL ; Transcriptome/genetics ; Microglia/metabolism/pathology/drug effects ; Tumor Microenvironment/immunology ; Female ; Humans ; }, abstract = {Interactions between metastatic cancer cells and the brain microenvironment regulate brain metastasis (BrMet) progression. Central nervous system (CNS)-native and peripheral immune cells influence the BrMet immune landscape, but the dynamics and factors modulating this microenvironment remain unclear. As the gut microbiome impacts CNS and peripheral immune activity, we investigated its role in regulating immune response dynamics throughout BrMet stages. Antibiotic-induced (ABX) gut dysbiosis significantly increased BrMet burden versus controls but was equalized with fecal matter transplantation, highlighting microbiome diversity as a regulator of BrMet. Single-cell sequencing revealed a highly dynamic immune landscape during BrMet progression in both conditions. However, the timing of the monocyte inflammatory response was altered. Microglia displayed an elevated activation signature in late-stage metastasis in ABX-treated mice. T cell and microglia perturbation revealed involvement of these cell types in modulating BrMet under gut dysbiosis. These data indicate profound effects on immune response dynamics imposed by gut dysbiosis across BrMet progression.}, }
@article {pmid40023320, year = {2025}, author = {Petracco, G and Faimann, I and Reichmann, F}, title = {Inflammatory bowel disease and neuropsychiatric disorders: Mechanisms and emerging therapeutics targeting the microbiota-gut-brain axis.}, journal = {Pharmacology &amp; therapeutics}, volume = {269}, number = {}, pages = {108831}, doi = {10.1016/j.pharmthera.2025.108831}, pmid = {40023320}, issn = {1879-016X}, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; *Inflammatory Bowel Diseases/therapy/microbiology/psychology/physiopathology/complications ; *Mental Disorders/therapy/microbiology ; *Brain/metabolism/physiopathology ; Fecal Microbiota Transplantation/methods ; *Brain-Gut Axis ; }, abstract = {Crohn's disease (CD) and ulcerative colitis (UC) are the two major entities of inflammatory bowel disease (IBD). These disorders are known for their relapsing disease course and severe gastrointestinal symptoms including pain, diarrhoea and bloody stool. Accumulating evidence suggests that IBD is not only restricted to the gastrointestinal tract and that disease processes are able to reach distant organs including the brain. In fact, up to 35 % of IBD patients also suffer from neuropsychiatric disorders such as generalized anxiety disorder and major depressive disorder. Emerging research in this area indicates that in many cases these neuropsychiatric disorders are a secondary condition as a consequence of the disturbed communication between the gut and the brain via the microbiota-gut-brain axis. In this review, we summarise the current knowledge on IBD-associated neuropsychiatric disorders. We examine the role of different pathways of the microbiota-gut-brain axis in the development of CNS disorders highlighting altered neural, immunological, humoral and microbial communication. Finally, we discuss emerging therapies targeting the microbiota-gut-brain axis to alleviate IBD and neuropsychiatric symptoms including faecal microbiota transplantation, psychobiotics, microbial metabolites and vagus nerve stimulation.}, }
@article {pmid40022204, year = {2025}, author = {Debray, R and Dickson, CC and Webb, SE and Archie, EA and Tung, J}, title = {Shared environments complicate the use of strain-resolved metagenomics to infer microbiome transmission.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {59}, pmid = {40022204}, issn = {2049-2618}, support = {R01 AG071684/AG/NIA NIH HHS/United States ; R61 AG078470/AG/NIA NIH HHS/United States ; R61AG078470//National Science Foundation/ ; R01AG071684/NH/NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Bacteria/classification/genetics/isolation &amp; purification ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Metagenome/genetics ; *Metagenomics/standards ; Papio/microbiology ; *Social Behavior ; *Environmental Microbiology ; Female ; Diet ; Rain ; }, abstract = {BACKGROUND: In humans and other social animals, social partners have more similar microbiomes than expected by chance, suggesting that social contact transfers microorganisms. Yet, social microbiome transmission can be difficult to identify based on compositional data alone. To overcome this challenge, recent studies have used information about microbial strain sharing (i.e., the shared presence of highly similar microbial sequences) to infer transmission. However, the degree to which strain sharing is influenced by shared traits and environments among social partners, rather than transmission per se, is not well understood.<br><br>RESULTS: Here, we first use a fecal microbiota transplant dataset to show that strain sharing can recapitulate true transmission networks under ideal settings when donor-recipient pairs are unambiguous and recipients are sampled shortly after transmission. In contrast, in gut metagenomes from a wild baboon population, we find that demographic and environmental factors can override signals of strain sharing among social partners.<br><br>CONCLUSIONS: We conclude that strain-level analyses provide useful information about microbiome similarity, but other facets of study design, especially longitudinal sampling and careful consideration of host characteristics, are essential for inferring the underlying mechanisms of strain sharing and resolving true social transmission network. Video Abstract.}, }
@article {pmid40020386, year = {2025}, author = {Zhang, W and Qi, X and Han, M and Jia, Q and Li, X and Yin, W and Wang, Y and Wu, H and Shao, H and Peng, C and Su, C and Sai, L}, title = {Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiota.}, journal = {Ecotoxicology and environmental safety}, volume = {292}, number = {}, pages = {117969}, doi = {10.1016/j.ecoenv.2025.117969}, pmid = {40020386}, issn = {1090-2414}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Sirtuin 1/metabolism ; Rats ; *Silicosis/drug therapy/pathology ; Male ; *Acetates/pharmacology ; Fecal Microbiota Transplantation ; Dysbiosis ; Lung/drug effects/pathology ; Pulmonary Fibrosis/drug therapy/chemically induced/pathology ; }, abstract = {Silicosis is a prevalent occupational disease marked by progressive pulmonary fibrosis. Despite its significant health burden, the pathogenesis of silicosis remains unclear, and no specific therapeutic drugs are available. In this study, we developed a novel intervention strategy targeting gut microbiota and investigated its underlying mechanisms. Using 16S rRNA gene sequencing, we observed significant gut microbiota dysbiosis in silicosis rats at different times (1-8 weeks), notably characterized by altered relative abundance of Ruminococcus and Lactobacillus. Fecal microbiota transplantation altered the gut microbiota structure of silicosis rats, alleviated silica-induced lung histopathological injury, with LEfSe analysis identifying Bifidobacterium as a potential biomarker. Treatment with Bifidobacterium reduced the level of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and fibrosis markers (collagen III, α-SMA and vimentin) in the lungs of silicosis rats, accompanied with increased serum acetic acid levels. Acetate, a major metabolite of Bifidobacterium, demonstrated similar protective effects against silicosis in this study, suggesting its role as a key mediator of Bifidobacterium action in the lungs. Both Bifidobacterium and acetate significantly upregulated Sirt1 in intestinal and lung tissues, while Sirt1 inhibition diminished their benefits to silicosis. As a widely studied histone deacetylase, Sirt1 was proven to be markedly reduced in the lungs of silicosis rats in this study. EX-527, a potent Sirt1 inhibitor, could worsen silicosis damage by upregulating the level of TGF-β1 and the degree of Smad2/3 acetylation. Our study highlights the efficacy of postbiotics, such as Bifidobacterium and acetate, and identifies Sirt1 as a promising target for silicosis treatment.}, }
@article {pmid40019272, year = {2025}, author = {Peng, C and Lei, P and Qi, H and Zhu, Q and Huang, C and Fu, J and Zhao, C}, title = {Effect of fecal microbiota transplantation on diabetic wound healing through the IL-17A-mTOR-HIF1α signaling axis.}, journal = {Applied and environmental microbiology}, volume = {91}, number = {3}, pages = {e0201924}, pmid = {40019272}, issn = {1098-5336}, support = {2021-ZJ-752//Qinghai Provincial Department of Science and Technology ()/ ; }, mesh = {Animals ; *Wound Healing ; Mice ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; *Fecal Microbiota Transplantation ; *TOR Serine-Threonine Kinases/metabolism ; Humans ; *Interleukin-17/metabolism ; *Diabetes Mellitus, Experimental/microbiology ; *Signal Transduction ; Male ; Mice, Inbred C57BL ; Gastrointestinal Microbiome ; Keratinocytes/microbiology/metabolism ; }, abstract = {UNLABELLED: Diabetes is the third most common chronic disorder worldwide. Diabetic wounds are a severe complication that is costly and often results in non-traumatic lower limb amputation. Recent investigations have demonstrated that the gut microbiota as a "virtual organ" can regulate metabolic diseases like diabetes. Fecal microbiota transplantation (FMT) is an innovative therapeutic approach for promoting wound healing, but its function remains incompletely defined. A diabetes model was established by supplying mice with a high-fat diet and performing an intraperitoneal injection of streptozotocin. Diabetic wounds were then created, followed by bacterial transplantation. The relevant indexes of wound healing were evaluated to verify the promoting effect of FMT on the diabetic wounds. Human skin keratinocytes were also cultured, and cell scratch experiments were conducted to further investigate the underlying mechanism. The FMT regulated the levels of specific bacteria in the diabetic mice and helped restore the balance of intestinal microbes. This transplantation also enhanced wound healing in the diabetic mice by augmenting the closure rate, accelerating re-epithelialization, and boosting collagen deposition in skin wounds. Furthermore, FMT promoted the production of IL-17A, which significantly enhanced the growth and movement of human keratinocytes. Inhibiting molecules related to the IL-17A-mTOR-HIF1α signaling axis were shown to hinder wound re-epithelialization.This study clarifies the function of the IL-17A-mTOR-HIF1α signaling axis in the utilization of FMT in diabetic wound healing, providing a new therapeutic method and target for promoting the healing of diabetic wounds.<br><br>IMPORTANCE: The Intestinal microbiota, as the organ with the largest number of microorganisms in the body, plays a crucial role in the physiological functions of the human body. Normal microbiota can be involved in various functions such as energy absorption, metabolism, and immunity of the body, and microbiota imbalance is related to many diseases such as obesity and diabetes. Diabetes, as one of the world's three major chronic diseases, is a significant health issue that troubles more than a billion people globally. Diabetic wounds are a problem that all diabetic patients must confront when undergoing surgery, and it is an important cause of non-traumatic amputations. Exploring the role of intestinal microorganisms in the wound-healing process of diabetic mice can offer the possibility of using microorganisms as a therapeutic means to intervene in clinically related diseases.}, }
@article {pmid40015179, year = {2025}, author = {Patra, D and Dev, G and Hand, TW and Overacre-Delgoffe, A}, title = {Friends close, enemies closer: the complex role of the microbiome in antitumor immunity.}, journal = {Current opinion in immunology}, volume = {93}, number = {}, pages = {102537}, doi = {10.1016/j.coi.2025.102537}, pmid = {40015179}, issn = {1879-0372}, mesh = {Humans ; *Neoplasms/immunology/therapy/microbiology ; *Immunotherapy/methods ; Animals ; *Microbiota/immunology ; Tumor Microenvironment/immunology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; }, abstract = {Immunotherapy has achieved remarkable advances in cancer treatment by harnessing the immune system to combat tumors, yet its effectiveness remains inconsistent across patients and tumor types. The microbiota, a diverse assemblage of microorganisms residing at host barrier surfaces, is pivotal in shaping immune responses. This review explores the direct and indirect mechanisms via which the microbiota modulates antitumor immune responses both locally within the tumor microenvironment and systemically by affecting distant tumors. We discuss recent findings linking microbiota-derived metabolites and microbiota-derived antigens with antitumor immunity and immunotherapy response. Additionally, we discuss recent advances in microbiome-based therapies, including fecal microbiota transplantation. We propose the use and development of new analytical techniques to further characterize the complex functions and interactions between the microbiome and immune system. To conclude, we outline recommendations for future research and therapeutic approaches to leverage the microbiome to improve current immunotherapies.}, }
@article {pmid40015156, year = {2025}, author = {Tang, L and Li, J and Luan, M and Qin, M and Zhong, C and Zhang, Y and Xie, Y and Shi, M and Qiu, L and Yu, J}, title = {Edgeworthia gardneri (Wall.) Meisn protects against HFD-induced murine atherosclerosis through improving gut microbiota-mediated intestinal barrier integrity.}, journal = {Atherosclerosis}, volume = {403}, number = {}, pages = {119132}, doi = {10.1016/j.atherosclerosis.2025.119132}, pmid = {40015156}, issn = {1879-1484}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Atherosclerosis/prevention &amp; control/microbiology/pathology/metabolism ; *Diet, High-Fat ; Disease Models, Animal ; Male ; Mice, Knockout, ApoE ; Mice, Inbred C57BL ; Plaque, Atherosclerotic ; *Intestinal Mucosa/metabolism/microbiology/drug effects ; Fecal Microbiota Transplantation ; Mice ; *Aortic Diseases/pathology/prevention &amp; control/microbiology/metabolism/genetics ; Aorta/pathology/drug effects/metabolism ; *Plant Extracts/pharmacology ; Tight Junctions/metabolism/drug effects ; Permeability ; Apolipoproteins E/genetics/deficiency ; }, abstract = {BACKGROUND: Gut microbiota plays a crucial role in the development and progression of atherosclerosis. Edgeworthia gardneri (Wall.) Meisn, a member of the Thymelaeaceae family and the Edgeworthia genus, has been previously shown in our studies to attenuate atherogenesis when administered orally as an ethanolic extract (EEEG). However, the interaction between EEEG and gut microbiota, and the mechanism by which gut microbiota exerts anti-atherosclerotic effects, remains unclear.<br><br>AIMS: This study aims to determine whether the anti-atherosclerotic properties of EEEG are associated with gut microbiota remodeling.<br><br>METHOD: Atherosclerosis was induced in ApoE[-/-] mice using a high-fat diet (HFD). The mice were treated with EEEG or Lactobacillus plantarum for 16 weeks. The composition of gut microbiota was analyzed through 16S rDNA sequencing. To assess whether the anti-atherosclerotic effects of EEEG depend on the gut microbiota, HFD-fed mice were treated with a cocktail of antibiotics or underwent fecal microbiota transplantation (FMT). Simultaneously, plaque areas in the aortic roots and whole aortas of apolipoprotein E deficient (ApoE[-/-]) mice were evaluated using oil red O staining and hematoxylin-eosin staining. Serum levels of LPS, fluorescein isothiocyanate-dextran, and expression levels of tight junction proteins were measured to identify the effects of EEEG on gut barrier dysfunction in HFD-fed ApoE[-/-] mice.<br><br>RESULTS: The results revealed that EEEG treatment significantly reduced atherosclerotic lesions by ameliorating lipid accumulation and preserving gut barrier integrity. The protective effects were abrogated by antibiotics administration, concomitant with an increase in gut barrier permeability by decreasing expression of tight junction proteins. The microbial analysis indicated an augmented abundance of Lactobacillus, Turicibacter, Faecalibacterium, Akkermansia, and Desulfovibrio following EEEG treatment. Meanwhile, transplantation of fecal microbiota from EEEG-treated mice exerted the anti-atherosclerotic effect in the high-fat diet (HFD)-fed ApoE[-/-] recipient mice, accompanied by improvement of gut barrier integrity through upregulation of tight junction protein expression. Furthermore, exogenous supplementation of Lactobacillus plantarum mitigated AS in ApoE[-/-] mice and improved the gut epithelial barrier function by increasing the expression level of Zo-1.<br><br>CONCLUSION: These results suggest that the anti-atherosclerotic efficacy of EEEG is attributed to the preservation of gut barrier integrity mediated by gut microbiota. EEEG and its enriched Lactobacillus plantarum may be promising adjuncts for AS management.<br><br>IMPORTANCE: Atherosclerosis (AS) is the primary pathological basis of cardiovascular disease (CVD). The gut microbiota is known to play an important role in the development and progression of atherosclerosis. In the clinical management of AS, pharmacological classes such as antioxidants, lipid-lowering drugs, and antiplatelet agents are commonly utilized. Despite their ability to decelerate the progression of AS, complications and adverse reactions still limit their application. Edgeworthia gardneri (Wall.) Meisn, a member of the Thymelaeaceae family and Edgeworthia Meisn genus, has been shown in previous studies to attenuate atherogenesis when orally administered as an ethanolic extract (EEEG). However, the interaction between EEEG and the gut microbiota, as well as the mechanism by which the gut microbiota exerts its anti-atherosclerotic effects, remain unclear. The significance of our research lies in identifying the mechanism behind the anti-atherosclerotic effect of Edgeworthia gardneri. The expected results will provide an important scientific basis for the clinical development and application of Edgeworthia gardneri in the prevention and treatment of AS.}, }
@article {pmid40013938, year = {2025}, author = {Hou, S and Yu, J and Li, Y and Zhao, D and Zhang, Z}, title = {Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {13}, pages = {e2413197}, pmid = {40013938}, issn = {2198-3844}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Dysbiosis/therapy/microbiology ; *Gastrointestinal Microbiome/physiology ; }, abstract = {This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.}, }
@article {pmid40012737, year = {2025}, author = {Yassin, LK and Nakhal, MM and Alderei, A and Almehairbi, A and Mydeen, AB and Akour, A and Hamad, MIK}, title = {Exploring the microbiota-gut-brain axis: impact on brain structure and function.}, journal = {Frontiers in neuroanatomy}, volume = {19}, number = {}, pages = {1504065}, pmid = {40012737}, issn = {1662-5129}, abstract = {The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. The MGBA serves as a conduit between the CNS and the ENS, facilitating communication between the emotional and cognitive centers of the brain via diverse pathways. In the initial stages of this review, we will examine the way how MGBA affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, brain blood barrier (BBB) structure and permeability, and synaptic structure. Furthermore, we will review the potential mechanistic pathways of neuroplasticity through MGBA influence. The short-chain fatty acids (SCFAs) play a pivotal role in the MGBA, where they can modify the BBB. We will therefore discuss how SCFAs can influence microglia, neuronal, and astrocyte function, as well as their role in brain disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD). Subsequently, we will examine the technical strategies employed to study MGBA interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), and antibiotics-induced dysbiosis. Finally, we will examine how particular bacterial strains can affect brain structure and function. By gaining a deeper understanding of the MGBA, it may be possible to facilitate research into microbial-based pharmacological interventions and therapeutic strategies for neurological diseases.}, }
@article {pmid40011318, year = {2025}, author = {Sedeek, SA and Farowski, F and Youssafi, S and Tsakmaklis, A and Brodesser, S and El-Attar, MM and Abdelmalek, MO and Vehreschild, MJGT}, title = {In vitro validation concept for lyophilized fecal microbiota products with a focus on bacterial viability.}, journal = {World journal of microbiology &amp; biotechnology}, volume = {41}, number = {3}, pages = {83}, pmid = {40011318}, issn = {1573-0972}, mesh = {Freeze Drying ; Humans ; *Feces/microbiology ; *Microbial Viability ; RNA, Ribosomal, 16S/genetics ; Bile Acids and Salts/analysis ; *Bacteria/genetics/isolation &amp; purification/classification/growth &amp; development ; *Fecal Microbiota Transplantation/methods ; Clostridium Infections/therapy/microbiology ; Germany ; }, abstract = {Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), typically administered as a fresh or frozen stool suspension through colonoscopy, nasojejunal tube, or oral capsules. Lyophilized fecal microbiota (LFM) are an alternative to frozen FM products. We aimed to assess whether lyophilization affects bacterial viability and metabolite levels and to develop LFM capsules for clinical use in Germany. Fecal donations from pre-screened volunteers were aliquoted and analyzed through microbial cell counting, bacterial culture, 16S rRNA gene amplicon sequencing, and bile acid assays. Results showed higher counts of viable bacterial cells and cultured anaerobes in unprocessed stool compared to freshly processed stool (p = 0.012 and p < 0.001, respectively). No significant difference in viable bacterial counts was found between freshly processed (day 0), lyophilized (day 3) and frozen FM (day 3) (p = 0.15), nor between freshly processed (day 0), lyophilized (days 30 and 90) and frozen FM (day 30) (p = 0.07). lyophilization did not significantly impact bile acid and 16S rRNA profiling. Encapsulation of lyophilized powder required fewer capsules (10-14) than frozen capsules (30). LFM products are a practical, viable alternative to frozen and fresh FM products, potentially improving storage and patient acceptance.}, }
@article {pmid40011195, year = {2025}, author = {Li, T and Chen, J and Xu, Y and Ji, W and Yang, S and Wang, X}, title = {Hawthorn Pectin Alleviates DSS-Induced Colitis in Mice by Ameliorating Intestinal Barrier Function and Modulating Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {10}, pages = {5872-5885}, doi = {10.1021/acs.jafc.4c07965}, pmid = {40011195}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Pectins/administration &amp; dosage ; Dextran Sulfate/adverse effects ; Mice ; Male ; *Crataegus/chemistry ; Colon/drug effects/metabolism/microbiology ; Humans ; *Colitis, Ulcerative/microbiology/drug therapy/chemically induced/metabolism/genetics ; *Intestinal Mucosa/metabolism/drug effects/microbiology ; Mice, Inbred C57BL ; Bacteria/classification/isolation &amp; purification/genetics/drug effects ; *Plant Extracts/administration &amp; dosage ; Tumor Necrosis Factor-alpha/genetics/immunology ; Interleukin-6/genetics/immunology ; Interleukin-1beta/genetics/immunology ; *Colitis/microbiology/chemically induced/drug therapy ; Occludin/genetics/metabolism ; Zonula Occludens-1 Protein/genetics/metabolism ; Intestinal Barrier Function ; }, abstract = {Pectin, as a kind of soluble dietary fiber in hawthorns, exhibits a wide range of biological activities. Nevertheless, its role and mechanism in ulcerative colitis (UC) remain unclear. In this study, the effect of hawthorn pectin (HP) against dextran sulfate sodium (DSS)-induced UC in mice and its underlying mechanism were evaluated. HP dramatically alleviated the pathological symptoms related to colitis in mice, displaying an increase in body weight and colon length and inhibition in colon damage. Importantly, HP inhibited the serum levels of inflammation-related factors including tumor necrosis factor-α, IL-1β, and IL-6 as well as decreased the number of F4/80-positive macrophages in the colon. Moreover, the expression levels of ZO-1 and occludin proteins related to intestinal permeability were increased. A significant decrease in a dose-dependent manner at the gut bacterial genus level (such as Alistipes, Colidextribacter, and Blautia) was observed after HP treatment. HP improved the metabolic pathways of gut microbiota and increased the concentrations of short-chain fatty acids in cecal contents of UC mice. Intriguingly, fecal microbiota transplantation intervention with an HP-derived microbiome notably increased the length and relieved histopathological changes of colon in UC mice. Conclusively, our study provided valuable insights into the potential of HP as a prebiotic for maintaining intestinal health and confirmed that HP could ameliorate UC in a gut microbiota-dependent manner.}, }
@article {pmid40010549, year = {2025}, author = {Wei, J and Chen, A and Huang, D and Teng, C and Cai, D and Wu, X and Wang, T and Hu, W and Huang, Z and Wang, P and Guan, X and Zheng, X and Chen, X}, title = {Gut microbiome-derived lipopolysaccharides aggravate cognitive impairment via TLR4-mediated inflammatory signaling in neonatal rats following hypoxic-ischemic brain damage.}, journal = {Brain, behavior, and immunity}, volume = {127}, number = {}, pages = {4-24}, doi = {10.1016/j.bbi.2025.02.029}, pmid = {40010549}, issn = {1090-2139}, abstract = {Hypoxic-ischemic brain damage (HIBD) is a leading cause of infant mortality and neurological disabilities in children. Recent evidence indicates that gut microbiota significantly contributes to the development of inflammation and cognitive impairments following brain injury. However, the mechanisms by which gut microbiota influence inflammation and cognitive function in the neonates after HIBD are not well understood. This study established a neonatal rat model of HIBD by the classic Rice-Vannucci technique to investigate gut dysbiosis following hypoxic-ischemic (HI) insult and to elucidate the causal relationship between gut dysbiosis and cognitive impairments. Our results demonstrated that HI insult resulted in significant gut microbial dysbiosis, characterized by an expansion of Enterobacteriaceae. This dysbiosis was associated with intestinal barrier damage, lipopolysaccharides (LPS) leakage, and systemic inflammation. Conversely, administration of aminoguanidine (AG) to inhibit Enterobacteriaceae overgrowth restored intestinal barrier integrity and reduced systemic inflammation. Importantly, AG treatment effectively suppressed microglial activation, neuronal damage, and cognitive impairments in the neonatal rats subjected to HI insult. Additionally, RNA sequencing analysis revealed that differentially expressed genes in both colonic and hippocampal tissues were primarily associated with inflammation and neuronal apoptosis after HI insult. Further mechanistic exploration revealed that AG treatment mitigated intestinal LPS leakage, thereby reducing the activation of the TLR4/MyD88/NF-κB signaling pathway and production of the downstream inflammatory cytokines in both the colon and hippocampus. Notably, fecal microbiota transplantation (FMT) from the HIBD rats to the antibiotic cocktail-treated recipient rats resulted in microglial activation, neuronal damage, and cognitive impairments in the recipients. However, these adverse effects were effectively mitigated in the recipient rats that received FMT from the AG-treated donors, as well as in those undergoing hippocampal TLR4 knockdown. In conclusion, our findings indicate that LPS derived from gut Enterobacteriaceae overgrowth plays a critical role in the TLR4-mediated inflammatory signaling, providing a novel microbiota-based therapeutic approach for cognitive impairments following neonatal HIBD.}, }
@article {pmid40008452, year = {2025}, author = {Chen, A and Teng, C and Wei, J and Wu, X and Zhang, H and Chen, P and Cai, D and Qian, H and Zhu, H and Zheng, X and Chen, X}, title = {Gut microbial dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2471015}, pmid = {40008452}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/complications ; Rats ; *Cognitive Dysfunction/microbiology/etiology ; *Hypoxia-Ischemia, Brain/complications/microbiology ; Animals, Newborn ; Fecal Microbiota Transplantation ; Toll-Like Receptor 4/genetics/metabolism ; Male ; Lipopolysaccharides/blood ; *Neuroinflammatory Diseases/microbiology/etiology ; Rats, Sprague-Dawley ; Disease Models, Animal ; Dexamethasone ; Intestines/microbiology/physiopathology ; }, abstract = {Neonatal hypoxic-ischemic brain damage (HIBD) is considered as a major cause of long-term cognitive impairments in newborns. It has been demonstrated that gut microbiota is closely associated with the prognosis of various neurological disorders. However, the role of microbiota-gut-brain axis on cognitive function following neonatal HIBD remains elusive. In this experiment, the correlation analysis supported the involvement of gut microbial changes following hypoxic-ischemic (HI) insult in the development of long-term cognitive impairments. Subsequent experiment revealed the involvement of the intestinal dysfunction in the hippocampal neuroinflammation and synaptic injury. In causal relationship validation experiments, fecal microbiota transplantation (FMT) from cognitively normal rats could restore gut microbial composition, improve intestinal dysfunction, reduce the serum levels of lipopolysaccharides (LPS) and inflammatory mediators, and alleviate neuroinflammation, synaptic damage and cognitive impairments in neonatal HIBD recipient rats. Conversely, the FMT from neonatal HIBD rats could induce above adverse pathological changes in the normal recipient rats. Moreover, oral administration of anti-inflammatory agent dexamethasone (DEX) exhibited the potential to alleviate these detrimental effects in neonatal HIBD rats, with the efficacy being partly reliant on gut microbiota. Further experiment on the potential molecular mechanisms using RNA sequencing indicated a significant increase in the toll-like receptor 4 (TLR4) gene in the intestinal tissues of neonatal HIBD rats. Additionally, the interventions such as TLR4 inhibitor TLR4-IN-C34 administration, FMT, and oral DEX were demonstrated to modulate intestinal function by inhibiting the LPS/TLR4 signaling pathway, thereby exerting neuroprotective effects. Collectively, these findings underscore the contribution of gut microbial dysbiosis post HI insult in activating the LPS/TLR4 signaling pathway, triggering intestinal inflammation and dysfunction, exacerbating systemic inflammation, and consequently worsening synaptic and cognitive impairments in neonatal HIBD rats. Hence, rectifying gut microbial dysbiosis or regulating intestinal function may represent a promising strategy for alleviating long-term cognitive impairments in neonates affected by HIBD.}, }
@article {pmid40008084, year = {2025}, author = {Zheng, J and Huang, Y and Zhang, L and Liu, T and Zou, Y and He, L and Guo, S}, title = {Role of the Gut-Lung Microbiome Axis in Airway Inflammation in OVA-Challenged Mice and the Effect of Azithromycin.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {2661-2676}, pmid = {40008084}, issn = {1178-7031}, abstract = {OBJECTIVE: This study aimed to investigate the role of the gut-lung microbiome axis in airway inflammation in asthma and to evaluate the effect of azithromycin on this axis, with a focus on the potential mechanism by which azithromycin reduces allergic airway inflammation.<br><br>METHODS: Haematoxylin and eosin (H&amp;E) and periodic acid-Schiff (PAS) staining were used to assess pathological changes in the lung tissues of asthmatic mice. Leukocyte cell types in bronchoalveolar lavage fluid (BALF) samples were quantified following Wright-Giemsa staining. Total IgE, OVA-specific IgE, IL-4, IL-6, and IL-17A levels in BALF and total IgE in serum were measured by ELISA. The respiratory and gut microbiota were analysed using 16S rRNA gene sequencing and subsequent taxonomic analysis.<br><br>RESULTS: OVA-challenged asthmatic mice with gut microbiota dysbiosis exhibited alterations in the respiratory microbiota, resulting in further aggravation of airway inflammation. Following faecal microbiota transplantation (FMT) to restore gut microbiota, respiratory microbiota dysbiosis was partially improved, and airway inflammation was significantly alleviated. Furthermore, azithromycin reduced airway inflammation in asthmatic mice, particularly non-eosinophilic inflammation, for which low-dose azithromycin combined with budesonide proved more effective. Azithromycin significantly enhanced the diversity and microbial composition of the gut microbiota and also affected the respiratory microbiota. At the phylum level, azithromycin decreased the abundance of Proteobacteria in the gut microbiota. At the genus level, azithromycin reduced the abundance of Pseudomonas in the respiratory microbiota.<br><br>CONCLUSION: The gut-lung microbiome axis plays a crucial role in airway inflammation in asthma. Azithromycin may reduce airway inflammation in asthma through modulation of the gut-lung microbiome axis.}, }
@article {pmid40007342, year = {2025}, author = {Wang, L and Zhang, Z and Chen, X and Wang, Z and Song, X and Geng, Z and Zhang, X and Wang, Y and Li, J and Hu, J and Zuo, L}, title = {Sakuranetin ameliorates experimental colitis in a gut microbiota-dependent manner.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {139}, number = {}, pages = {156540}, doi = {10.1016/j.phymed.2025.156540}, pmid = {40007342}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis/drug therapy/chemically induced/microbiology ; Mice ; Dextran Sulfate ; Fatty Acids, Volatile/metabolism ; Dysbiosis/drug therapy ; Male ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Feces/chemistry/microbiology ; Disease Models, Animal ; Colon/drug effects/pathology ; Intestinal Mucosa/drug effects ; *Anti-Inflammatory Agents/pharmacology ; }, abstract = {BACKGROUND: The progression of inflammatory bowel disease (IBD) is closely connected with intestinal flora dysbiosis. Sakuranetin (SAK) is a natural compound with anti-inflammatory and antibiosis activities. We investigated the properties and mechanisms of SAK on IBD-like colitis.<br><br>METHODS: Mice with dextran sulfate sodium (DSS)-induced colitis were accomplished to assess the effects of SAK on colitis, as well as intestinal mucosal immune imbalance and intestinal barrier dysfunction. 16S rDNA was used to characterize the intestinal flora, and the short-chain fatty acid (SCFA) content in faeces was calculated using GS&#x2012;MS. Faecal microbiota transplantation (FMT) and a pseudosterile model (antibiotic cocktail, ABX) were used to evaluate whether the effects of SAK on colitis were dependent on the gut flora. Pathohistological and biochemical tests were used to estimate the safety of SAK.<br><br>RESULTS: SAK significantly ameliorated DSS-induced colitis in mice, verified by decreased weight loss, less colon shortening, and lower disease activity, histology and colonoscopy scores. Moreover, SAK alleviated gut dysbiosis and elevated the abundance of SCFA-producing bacteria in DSS-treated mice. Meanwhile, SAK increased faecal SCFA levels and activated GPR41/43 signalling. SAK also improved Treg/Th17 homeostasis and intestinal barrier function. In addition, ABX and FMT experiments confirmed that the ability of SAK to alleviate colitis was mediated through the gut flora. Finally, a safety experiment revealed that SAK had no significant adverse effects on major organ or liver/kidney function.<br><br>CONCLUSIONS: SAK may improve the intestinal immune balance and barrier function by regulating intestinal flora dysbiosis and increasing SCFA production, thereby protecting against colitis.}, }
@article {pmid40007058, year = {2025}, author = {Ge, P and Guo, Y and Che, B and Jin, H and Chen, L and Chen, Z and Tang, K}, title = {Modulation of NLRP3 Inflammasome Activation by QYHT Decoction: Implications for the Treatment of Erectile Dysfunction in Hyperuricemia.}, journal = {American journal of men's health}, volume = {19}, number = {1}, pages = {15579883251318307}, pmid = {40007058}, issn = {1557-9891}, mesh = {Male ; Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/drug effects/metabolism ; Rats ; *Erectile Dysfunction/drug therapy/etiology/therapy ; *Inflammasomes/drug effects/metabolism ; Humans ; *Hyperuricemia/complications ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Gastrointestinal Microbiome/drug effects ; Middle Aged ; Oxidative Stress/drug effects ; Rats, Sprague-Dawley ; Fecal Microbiota Transplantation ; Disease Models, Animal ; }, abstract = {Hyperuricemia (HUA) causes vascular endothelial dysfunction and oxidative stress, and simultaneously activates the NLRP3 inflammasome, leading to inflammatory reactions and erectile dysfunction (ED). This study aimed to investigate the effects of QYHT (Quyuhuatanerxian decoction) decoction on the NLRP3 inflammasome and explore its potential in treating HUA-induced ED. This study employed four treatment methods: (a) treating HUA-induced ED patients with QYHT and analyzing changes in gut microbiota abundance and fecal metabolites through 16S sequencing; (b) establishing an HUA-induced ED rat model, treating with different doses of QYHT, and examining changes in serum metabolites; (c) conducting fecal microbiota transplantation (FMT) therapy; evaluating erectile function, oxidative stress, inflammatory response, and NLRP3 inflammasome activation levels; and (d) exploring key monomeric compounds and potential targets in QYHT through network pharmacology and molecular docking. The treatment with QYHT and FMT increased testosterone levels, reduced oxidative stress and inflammatory marker levels, and inhibited the expressions of NLRP3-related factors. QYHT affected the gut microbiota structure and metabolite levels. The key components were linoleoyl acetate and mandanol, and the target was JAK2. QYHT decoction regulates the distribution of gut microbiota, improves amino acid metabolism, and effectively inhibits the activation of NLRP3 inflammasomes. This, in turn, enhances erectile function and reduces oxidative stress and inflammatory response levels, leading to successful treatment of HUA-induced ED.}, }
@article {pmid40005809, year = {2025}, author = {Parodi, E and Novi, M and Bottino, P and La Porta, E and Merlotti, G and Castello, LM and Gotta, F and Rocchetti, A and Quaglia, M}, title = {The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005809}, issn = {2076-2607}, abstract = {The role of gut microbiota (GM) and intestinal dysbiosis in triggering the onset and/or modulating the severity and progression of lupus nephritis (LN) has been the object of intense research over the last few years. Some alterations at the phyla level, such as the abundance of Proteobacteria and reduction in Firmicutes/Bacteroidetes (F/B) ratio and in α-diversity have been consistently reported in systemic lupus erythematosus (SLE), whereas a more specific role has been ascribed to some species (Bacteroides thetaiotaomicron and Ruminococcus gnavus) in LN. Underlying mechanisms include microbial translocation through a "leaky gut" and subsequent molecular mimicry, immune dysregulation (alteration of IFNγ levels and of balance between Treg and Th17 subsets), and epigenetic interactions. Levels of bacterial metabolites, such as butyrate and other short-chain fatty acids (SCFAs), appear to play a key role in modulating LN. Beyond bacterial components of GM, virome and mycobiome are also increasingly recognized as important players in the modulation of an immune response. On the other hand, microbiota-based therapy appears promising and includes diet, prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). The modulation of microbiota could correct critical alterations, such as F/B ratio and Treg/Th17 imbalance, and blunt production of autoantibodies and renal damage. Despite current limits, GM is emerging as a powerful environmental factor that could be harnessed to interfere with key mechanisms leading to SLE, preventing flares and organ damage, including LN. The aim of this review is to provide a state-of-the-art analysis of the role of GM in triggering and modulating SLE and LN on the one hand, while exploring possible therapeutic manipulation of GM to control the disease on the other hand.}, }
@article {pmid40005733, year = {2025}, author = {Romano, FS and Lallo, MA and Romano, RS and Isidoro, LPS and Cardoso, MR and Sodré, LC and Melchert, A and Guimarães-Okamoto, PTC and Pappalardo, MCF and Amaral, AR and Vendramini, THA}, title = {Fecal Microbiota Transplantation as a Treatment for Granulomatous Colitis in a French Bulldog: A Case Report.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005733}, issn = {2076-2607}, abstract = {Granulomatous colitis, or ulcerative colitis, is an infectious and inflammatory disease that primarily affects the colon and occasionally extends to the ileum, particularly in young Boxer and French Bulldogs. Unlike typical chronic colitis in small animals, the early onset of the disease suggests a genetic predisposition. The condition is characterized by the overgrowth of Escherichia coli, specifically the enteroinvasive variant, which displaces beneficial gut bacteria, contributing to its infectious nature. Secondary dysbiosis and chronic-active inflammation involving histiocytes and other leukocytic infiltrates are prominent features. Clinical manifestations include chronic diarrhea with blood and mucus, frequent tenesmus, and pain, with variable degrees of weight loss depending on disease severity. The final diagnosis is based on clinical history (chronic diarrhea with hematochezia), macroscopic findings from colonoscopy (edema, ulcers, and wall hyperplasia), histopathology (presence of histiocytes), and Escherichia coli growth in culture from a colon fragment. Treatment is guided by colon antibiograms, which often require prolonged antibiotic therapy. Fecal microbiota transplantation (FMT) has emerged as a potential treatment, either as a primary intervention or adjunctive therapy, for conditions such as acute enteritis (e.g., canine parvovirus), dysbiosis, and chronic enteropathies. However, its application to modulate the microbiota and reduce inflammation in granulomatous colitis, potentially leading to longer intervals between relapses, remains an area of ongoing investigation. This is a case report of a French Bulldog diagnosed with ulcerative colitis accompanied by dysbiosis and refractory to standard treatments but sensitive and partially responsive to amikacin. The patient achieved control and sustained improvement in fecal scoring following fecal transplantation. This approach prevented the need for additional antibiotic therapy, ensuring clinical amelioration alongside microbiome restoration.}, }
@article {pmid40005617, year = {2025}, author = {Kaltsas, A and Giannakodimos, I and Markou, E and Adamos, K and Stavropoulos, M and Kratiras, Z and Zachariou, A and Dimitriadis, F and Sofikitis, N and Chrisofos, M}, title = {The Role of Gut Microbiota Dysbiosis in Erectile Dysfunction: From Pathophysiology to Treatment Strategies.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005617}, issn = {2076-2607}, abstract = {Erectile dysfunction (ED) is a prevalent male sexual disorder characterized by the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. While its etiology is multifactorial, encompassing vascular, neurological, hormonal, and psychological components, emerging evidence suggests a significant role for gut microbiota dysbiosis in its development. The gut microbiota influences various metabolic, inflammatory, and neuropsychological processes critical to erectile function. Dysbiosis can lead to systemic inflammation, endothelial dysfunction, hormonal imbalances, and altered neurotransmitter production, all of which are key factors in ED pathogenesis. This narrative review synthesizes current research on the association between gut microbiota alterations and ED, highlighting specific bacterial taxa implicated in ED through mechanisms involving inflammation, metabolic disturbances, and hormonal regulation. This review explores potential mechanisms linking gut microbiota and ED, including pro-inflammatory cytokines, gut barrier integrity disruption, metabolic disorders, psychological factors via the gut-brain axis, and hormonal regulation. Furthermore, the gut microbiota offers promising avenues for developing non-invasive biomarkers and therapeutic interventions such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation. Future research should focus on longitudinal studies, mechanistic explorations, and clinical trials to validate these findings and translate them into clinical practice. Understanding the interplay between the gut microbiota and erectile function could unveil novel diagnostic biomarkers and pave the way for innovative treatments targeting the microbiota, ultimately improving men's sexual and overall health.}, }
@article {pmid40005608, year = {2025}, author = {Pasta, A and Formisano, E and Calabrese, F and Marabotto, E and Furnari, M and Bodini, G and Torres, MCP and Pisciotta, L and Giannini, EG and Zentilin, P}, title = {From Dysbiosis to Hepatic Inflammation: A Narrative Review on the Diet-Microbiota-Liver Axis in Steatotic Liver Disease.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005608}, issn = {2076-2607}, abstract = {The gut microbiota has emerged as a critical player in metabolic and liver health, with its influence extending to the pathogenesis and progression of steatotic liver diseases. This review delves into the gut-liver axis, a dynamic communication network linking the gut microbiome and liver through metabolic, immunological, and inflammatory pathways. Dysbiosis, characterized by altered microbial composition, contributes significantly to the development of hepatic steatosis, inflammation, and fibrosis via mechanisms such as gut barrier dysfunction, microbial metabolite production, and systemic inflammation. Dietary patterns, including the Mediterranean diet, are highlighted for their role in modulating the gut microbiota, improving gut-liver axis integrity, and attenuating liver injury. Additionally, emerging microbiota-based interventions, such as fecal microbiota transplantation and bacteriophage therapy, show promise as therapeutic strategies for steatotic liver disease. However, challenges such as population heterogeneity, methodological variability, and knowledge gaps hinder the translational application of current findings. Addressing these barriers through standardized approaches and integrative research will pave the way for microbiota-targeted therapies to mitigate the global burden of steatotic liver disease.}, }
@article {pmid40005065, year = {2025}, author = {Noureldein, MH and Rumora, AE and Teener, SJ and Rigan, DM and Hayes, JM and Mendelson, FE and Carter, AD and Rubin, WG and Savelieff, MG and Feldman, EL}, title = {Dietary Fatty Acid Composition Alters Gut Microbiome in Mice with Obesity-Induced Peripheral Neuropathy.}, journal = {Nutrients}, volume = {17}, number = {4}, pages = {}, pmid = {40005065}, issn = {2072-6643}, support = {1R01DK130913-00A1/NH/NIH HHS/United States ; U24 DK076169/DK/NIDDK NIH HHS/United States ; 1R00DK119366-00A1/NH/NIH HHS/United States ; U24 DK115255/DK/NIDDK NIH HHS/United States ; P30DK020572//Michigan Diabetes Research Center/ ; not applicable//Richard and Jane Manoogian Foundation/ ; not applicable//Dr. John H. Doran Neuropathy Research Initiative/ ; not applicable//Taubman Foundation/ ; P30 DK020572/DK/NIDDK NIH HHS/United States ; not applicable//Nathan and Rose Milstein Research Fund/ ; P30 DK063608/DK/NIDDK NIH HHS/United States ; not applicable//Sinai Medical Staff Foundation/ ; 1K99AG081390-00A1/NH/NIH HHS/United States ; 1R01DK076169-00A1/NH/NIH HHS/United States ; 1R01DK115255-00A1/NH/NIH HHS/United States ; K99 AG081390/AG/NIA NIH HHS/United States ; 1P30DK063608-00A20/NH/NIH HHS/United States ; R01 DK130913/DK/NIDDK NIH HHS/United States ; not applicable//NeuroNetwork for Emerging Therapies/ ; R00 DK119366/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Obesity/complications/microbiology ; Mice ; Diet, High-Fat/adverse effects ; *Peripheral Nervous System Diseases/etiology/microbiology ; *Fatty Acids/administration &amp; dosage ; Male ; Mice, Inbred C57BL ; *Dietary Fats/administration &amp; dosage ; Fecal Microbiota Transplantation ; Fatty Acids, Monounsaturated/administration &amp; dosage ; Disease Models, Animal ; }, abstract = {BACKGROUND: Peripheral neuropathy (PN), a complication of diabetes and obesity, progresses through a complex pathophysiology. Lifestyle interventions to manage systemic metabolism are recommended to prevent or slow PN, given the multifactorial risks of diabetes and obesity. A high-fat diet rich in saturated fatty acids (SFAs) induces PN, which a diet rich in monounsaturated fatty acids (MUFAs) rescues, independent of weight loss, suggesting factors beyond systemic metabolism impact nerve health. Interest has grown in gut microbiome mechanisms in PN, which is characterized by a distinct microbiota signature that correlates with sciatic nerve lipidome.<br><br>METHODS: Herein, we postulated that SFA- versus MUFA-rich diet would impact gut microbiome composition and correlate with PN development. To assess causality, we performed fecal microbiota transplantation (FMT) from donor mice fed SFA- versus MUFA-rich diet to lean recipient mice and assessed metabolic and PN phenotypes.<br><br>RESULTS: We found that the SFA-rich diet altered the microbiome community structure, which the MUFA-rich diet partially reversed. PN metrics correlated with several microbial families, some containing genera with feasible mechanisms of action for microbiome-mediated effects on PN. SFA and MUFA FMT did not impact metabolic phenotypes in recipient mice although SFA FMT marginally induced motor PN.<br><br>CONCLUSIONS: The involvement of diet-mediated changes in the microbiome on PN and gut-nerve axis may warrant further study.}, }
@article {pmid40004205, year = {2025}, author = {Blanquet, L and Serra, D and Marrinhas, C and Almeida, A}, title = {Exploring Gut Microbiota-Targeted Therapies for Canine Idiopathic Epilepsy.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40004205}, issn = {1422-0067}, mesh = {Animals ; Dogs ; *Gastrointestinal Microbiome/drug effects ; *Epilepsy/veterinary/microbiology/therapy ; *Dog Diseases/therapy/microbiology ; Dysbiosis/microbiology ; }, abstract = {Epilepsy stands out as one of the most prevalent chronic neurological conditions affecting companion animals. Recent research has increasingly focused on exploring the role of gut microbiota in influencing neurological conditions, like epilepsy. This influence stems from the bidirectional communication pathways between gut bacteria and the brain, which involve metabolic, neural, immunological, and endocrine mechanisms. In fact, a balanced and stable gut microbiota is essential to maintaining normal gut physiology and ensuring appropriate signaling along the gut-brain axis. Conversely, dysbiosis can have detrimental effects on gut physiology and may contribute to the development or exacerbation of neurological conditions, including epilepsy. Considering these findings, this review article aims to deepen the understanding of the mechanisms underlying the microbiota-gut-brain connection in the context of canine idiopathic epilepsy. Moreover, this review presents recent data on innovative gut-related therapeutic strategies for canine idiopathic epilepsy treatment.}, }
@article {pmid40004161, year = {2025}, author = {Wang, Z and Ma, X and Shi, W and Zhu, W and Feng, X and Xin, H and Zhang, Y and Cong, B and Li, Y}, title = {The Gut Microbiota Metabolite Butyrate Modulates Acute Stress-Induced Ferroptosis in the Prefrontal Cortex via the Gut-Brain Axis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40004161}, issn = {1422-0067}, support = {82072109//National Natural Science Foundation of China/ ; 82130055//National Natural Science Foundation of China/ ; 82293651//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Prefrontal Cortex/metabolism/pathology/drug effects ; Mice ; *Ferroptosis/drug effects ; Male ; *Stress, Psychological/metabolism/microbiology ; Depression/metabolism/microbiology ; *Butyrates/metabolism/pharmacology ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; *Brain-Gut Axis ; Disease Models, Animal ; Neurons/metabolism ; }, abstract = {Stress has been implicated in the onset of mental disorders such as depression, with the prefrontal cortex (PFC) playing a crucial role. However, the underlying mechanisms remain to be fully elucidated. Metabolites secreted by intestinal flora can enter the bloodstream and exert regulatory effects on the body. Consequently, this study aims to investigate the molecular mechanisms by which gut flora influences ferroptosis in PFC neurons, thereby affecting depression-like behavioral changes in mice subjected to acute stress. Initially, we established a mouse model of acute restraint stress (3-day duration) and verified that stress-induced ferroptosis of PFC neurons contributed to depression-like behavioral alterations in mice, as evidenced by morphological, behavioral, and molecular biology assessments. Subsequently, through fecal microbiota transplantation (FMT) experiments, we established a significant correlation between gut microbiota and ferroptosis of PFC neurons in acute stress-exposed mice. 16S rDNA sequencing identified butyric acid-producing bacteria, specifically g_Butyricimonas and its primary metabolite, butyric acid, as critical regulators of ferroptosis in PFC neurons in acutely stressed mice. Furthermore, the intervention of butyrate demonstrated its potential to ameliorate damage to the intestinal and blood-brain barriers in these mice. This intervention also mitigated depression-like behaviors induced by ferroptosis of PFC neurons by alleviating systemic inflammatory responses. The findings of this study indicate that acute stress-induced ferroptosis of PFC neurons plays a critical role in depression-like behavioral changes in mice. Additionally, the gut microbiota metabolite butyrate can modulate ferroptosis and depression-like behavioral changes through the gut-brain axis.}, }
@article {pmid40004115, year = {2025}, author = {Zhang, J and Wei, J and Lai, W and Sun, J and Bai, Y and Cao, H and Guo, J and Su, Z}, title = {Focus on Glucagon-like Peptide-1 Target: Drugs Approved or Designed to Treat Obesity.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40004115}, issn = {1422-0067}, mesh = {Humans ; *Obesity/drug therapy/metabolism ; *Glucagon-Like Peptide 1/metabolism ; *Anti-Obesity Agents/therapeutic use/pharmacology ; Animals ; Glucagon-Like Peptide-1 Receptor Agonists ; Glucagon-Like Peptide-1 Receptor/metabolism ; }, abstract = {Obesity is closely related to metabolic diseases, which brings a heavy burden to the health care system. It is urgent to formulate and implement effective treatment strategies. Glucagon-like peptide-1 (GLP-1) is a protein with seven transmembrane domains connected by type B and G proteins, which is widely distributed and expressed in many organs and tissues. GLP-1 analogues can reduce weight, lower blood pressure, and improve blood lipids. Obesity, diabetes, cardiovascular diseases, and other diseases have caused scientists' research and development boom. Among them, GLP-1R agonist drugs have developed rapidly in weight-loss drugs. In this paper, based on the target of GLP-1, the mechanism of action of GLP-1 in obesity treatment was deeply studied, and the drugs approved and designed for obesity treatment based on GLP-1 target were elaborated in detail. Innovatively put forward and summarized the double and triple GLP-1 targeted drugs in the treatment of obesity with better effects and less toxic and side effects, and this can make full use of multi-target methods to treat other diseases in the future. Finally, it is pointed out that intestinal flora and microorganisms have many benefits in the treatment of obesity, and fecal bacteria transplantation may be a potential treatment for obesity with less harm to the body. This article provides some promising methods to treat obesity, which have strong practical value.}, }
@article {pmid40003979, year = {2025}, author = {Flynn, CK and Adams, JB and Krajmalnik-Brown, R and Khoruts, A and Sadowsky, MJ and Nirmalkar, K and Takyi, E and Whiteley, P}, title = {Review of Elevated Para-Cresol in Autism and Possible Impact on Symptoms.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40003979}, issn = {1422-0067}, support = {N/A//Zoowalk for Autism Research/ ; }, mesh = {*Cresols/metabolism/urine ; Humans ; Animals ; Gastrointestinal Microbiome ; *Autistic Disorder/metabolism ; *Autism Spectrum Disorder/metabolism ; Sulfuric Acid Esters/metabolism/urine ; Brain/metabolism ; Mice ; Renal Insufficiency, Chronic/metabolism ; }, abstract = {Para-cresol (p-cresol), and its primary human metabolite p-cresol sulfate (pCS), are among the most studied gut-derived metabolites relevant to autism spectrum disorder (ASD). P-cresol is produced by bacterial modification of phenylalanine or tyrosine and is one of many potentially deleterious metabolites produced by the gut microbiota. Seventeen studies have observed p-cresol and/or p-cresol sulfate as being higher in the urine of children with autism spectrum disorder (ASD) vs. controls. P-cresol has harmful effects on the body, including within the gut, brain, kidneys, liver, immune system, and mitochondria. Some of these effects may contribute to autism and comorbid symptoms. In the gut, p-cresol acts as an antibiotic, altering the gut microbiome to favor the bacteria that produce it. In the mitochondria, p-cresol disrupts ATP production and increases oxidative stress, which is also common in autism. In the brain, p-cresol impairs neuronal development. P-cresol inactivates dopamine beta-hydroxylase, which converts dopamine to noradrenaline. P-cresol sulfate impairs kidney function and is linked to chronic kidney disease (CKD), which is more common in ASD adults. P-cresol also interferes with immune function. Three animal studies have demonstrated that p-cresol causes autism-related symptoms in mice, and that mice can be recovered by the administration of fecal microbiota transplant from healthy mice. Similarly, it was found that microbiota transplant therapy treatment in children with ASD significantly reduced p-cresol sulfate levels to normal and led to significant improvements in gastrointestinal (GI) and ASD symptoms. In summary, p-cresol and pCS likely contribute to ASD core symptoms in a substantial subset of children with ASD.}, }
@article {pmid40003971, year = {2025}, author = {Yu, F and Zhu, C and Wu, W}, title = {Senile Osteoarthritis Regulated by the Gut Microbiota: From Mechanisms to Treatments.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40003971}, issn = {1422-0067}, support = {11DZ2261100//Shanghai Key Laboratory of Human Performance/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Osteoarthritis/therapy/microbiology/etiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; Aging ; Animals ; Medicine, Chinese Traditional ; }, abstract = {Osteoarthritis (OA) is a chronic, progressive degenerative joint disease that affects the entire synovial joint, leading to the progressive degeneration of articular cartilage. It seriously affects the quality of life and global disability of patients. OA is affected by a variety of factors; the most significant risk factor for OA is age. As individuals age, the risk and severity of OA increase due to the exacerbation of cartilage degeneration and wear and tear. In recent years, research has indicated that the gut microbiota may play a significant role in the aging and OA processes. It is anticipated that regulating the gut microbiota may offer novel approaches to the treatment of OA. The objective of this paper is to examine the relationship between the gut microbiota and senile OA, to investigate the potential mechanisms involved. This review also summarizes the therapeutic strategies related to gut flora in OA management, such as prebiotics and probiotics, diet, exercise, traditional Chinese medicine (TCM) modification, and fecal microbiota transplantation (FMT), highlighting the potential clinical value of gut flora and elucidating the current challenges. The foundation for future research directions is established through the summarization of current research progress.}, }
@article {pmid40003268, year = {2025}, author = {Todor, SB and Ichim, C}, title = {Microbiome Modulation in Pediatric Leukemia: Impact on Graft-Versus-Host Disease and Treatment Outcomes: A Narrative Review.}, journal = {Children (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {40003268}, issn = {2227-9067}, abstract = {The gut microbiome significantly influences the outcomes of pediatric leukemia, particularly in patients undergoing hematopoietic stem cell transplantation (HSCT). Dysbiosis, caused by chemotherapy, antibiotics, and immune system changes, contributes to complications such as graft-versus-host disease (GVHD), gastrointestinal issues, and infections. Various microbiome-related interventions, including prebiotics, probiotics, postbiotics, and fecal microbiota transplantation (FMT), have shown potential in mitigating these complications. Specific microbial signatures have been linked to GVHD risk, and interventions like inulin, Lactobacillus, and SCFAs (short-chain fatty acids), particularly butyrate, may help modulate the immune system and improve outcomes. FMT, while showing promising results in restoring microbial balance and alleviating GVHD, still requires careful monitoring due to potential risks in immunocompromised patients. Despite positive findings, more research is needed to optimize microbiome-based therapies and ensure their safety and efficacy in pediatric leukemia care.}, }
@article {pmid40002939, year = {2025}, author = {Vučinić, D and Redžović, A and Hauser, G and Mikolašević, I}, title = {Microbiota and Radiotherapy: Unlocking the Potential for Improved Gastrointestinal Cancer Treatment.}, journal = {Biomedicines}, volume = {13}, number = {2}, pages = {}, pmid = {40002939}, issn = {2227-9059}, abstract = {Radiotherapy (RT) is one of the major cornerstones in managing gastrointestinal (GI) cancers. However, several side effects, such as intestinal inflammation, mucosal injury, and dysbiosis, often compromise this. The gut microbiota increasingly attracts much interest as an essential modulator of RT effects influencing immune responses and tissue repair. Through short-chain fatty acids such as butyrate, representatives of certain bacterial species play a crucial role under normal conditions, keeping the mucosal integrity intact and reducing oxidative stress-mediated damage. Dysbiosis, a state where diminished microbial diversity and increased pathogenic species in the microbiota are seen, amplifies RT-induced toxicity in patients. Clinical investigations highlight that microbiota-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, hold the means to augment RT efficacy and lessen toxicity. Increased microflora diversity and specific microbial profiles have yielded serious patient improvements. Advanced RT methods use stereotactic body radiotherapy combined with microbiota modulation as a promising technique to shield healthy tissue and maximize immune-mediated antitumor effects. Additionally, there is an implication in tumor behavior regulated by the intratumoral microbiota regarding the response to radiotherapy. Notably, the modulation of gut and tumor microbiota provides an avenue to optimize RT benefits in GI cancers, underscoring the importance of personalized therapy.}, }
@article {pmid40002835, year = {2025}, author = {Mafe, AN and Büsselberg, D}, title = {Microbiome Integrity Enhances the Efficacy and Safety of Anticancer Drug.}, journal = {Biomedicines}, volume = {13}, number = {2}, pages = {}, pmid = {40002835}, issn = {2227-9059}, support = {NPRP 14S0311-210033//QNRF/ ; }, abstract = {The intricate relationship between anticancer drugs and the gut microbiome influences cancer treatment outcomes. This review paper focuses on the role of microbiome integrity in enhancing the efficacy and safety of anticancer drug therapy, emphasizing the pharmacokinetic interactions between anticancer drugs and the gut microbiota. It explores how disruptions to microbiome composition, or dysbiosis, can alter drug metabolism, immune responses, and treatment side effects. By examining the mechanisms of microbiome disruption caused by anticancer drugs, this paper highlights specific case studies of drugs like cyclophosphamide, 5-fluorouracil, and irinotecan, and their impact on microbial diversity and clinical outcomes. The review also discusses microbiome-targeted strategies, including prebiotics, probiotics, postbiotics, and fecal microbiota transplantation (FMT), as promising interventions to enhance cancer treatment. Furthermore, the potential of microbiome profiling in personalizing therapy and integrating these interventions into clinical practice is explored. Finally, this paper proposes future research directions, including developing novel biomarkers and a deeper comprehension of drug-microbiome interactions, to respond to current gaps in knowledge and improve patient outcomes in cancer care.}, }
@article {pmid40002529, year = {2025}, author = {Kalaga, P and Ray, SK}, title = {Mental Health Disorders Due to Gut Microbiome Alteration and NLRP3 Inflammasome Activation After Spinal Cord Injury: Molecular Mechanisms, Promising Treatments, and Aids from Artificial Intelligence.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, pmid = {40002529}, issn = {2076-3425}, support = {R01 CA091460/CA/NCI NIH HHS/United States ; R01 NS057811/NS/NINDS NIH HHS/United States ; }, abstract = {Aside from its immediate traumatic effects, spinal cord injury (SCI) presents multiple secondary complications that can be harmful to those who have been affected by SCI. Among these secondary effects, gut dysbiosis (GD) and the activation of the NOD (nucleotide-binding oligomerization domain) like receptor-family pyrin-domain-containing three (NLRP3) inflammasome are of special interest for their roles in impacting mental health. Studies have found that the state of the gut microbiome is thrown into disarray after SCI, providing a chance for GD to occur. Metabolites such as short-chain fatty acids (SCFAs) and a variety of neurotransmitters produced by the gut microbiome are hampered by GD. This disrupts healthy cognitive processes and opens the door for SCI patients to be impacted by mental health disorders. Additionally, some studies have found an increased presence and activation of the NLRP3 inflammasome and its respective parts in SCI patients. Preclinical and clinical studies have shown that NLRP3 inflammasome plays a key role in the maturation of pro-inflammatory cytokines that can initiate and eventually aggravate mental health disorders after SCI. In addition to the mechanisms of GD and the NLRP3 inflammasome in intensifying mental health disorders after SCI, this review article further focuses on three promising treatments: fecal microbiome transplants, phytochemicals, and melatonin. Studies have found these treatments to be effective in combating the pathogenic mechanisms of GD and NLRP3 inflammasome, as well as alleviating the symptoms these complications may have on mental health. Another area of focus of this review article is exploring how artificial intelligence (AI) can be used to support treatments. AI models have already been developed to track changes in the gut microbiome, simulate drug-gut interactions, and design novel anti-NLRP3 inflammasome peptides. While these are promising, further research into the applications of AI for the treatment of mental health disorders in SCI is needed.}, }
@article {pmid40002492, year = {2025}, author = {Gao, A and Lv, J and Su, Y}, title = {The Inflammatory Mechanism of Parkinson's Disease: Gut Microbiota Metabolites Affect the Development of the Disease Through the Gut-Brain Axis.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, pmid = {40002492}, issn = {2076-3425}, support = {Grant No. 81601330-YS//National Natural Science Foundation of China/ ; Grant No. 2022CFB178-YS//Natural Science Foundation of Hubei Province/ ; }, abstract = {Parkinson's disease is recognized as the second most prevalent neurodegenerative disorder globally, with its incidence rate projected to increase alongside ongoing population growth. However, the precise etiology of Parkinson's disease remains elusive. This article explores the inflammatory mechanisms linking gut microbiota to Parkinson's disease, emphasizing alterations in gut microbiota and their metabolites that influence the disease's progression through the bidirectional transmission of inflammatory signals along the gut-brain axis. Building on this mechanistic framework, this article further discusses research methodologies and treatment strategies focused on gut microbiota metabolites, including metabolomics detection techniques, animal model investigations, and therapeutic approaches such as dietary interventions, probiotic treatments, and fecal transplantation. Ultimately, this article aims to elucidate the relationship between gut microbiota metabolites and the inflammatory mechanisms underlying Parkinson's disease, thereby paving the way for novel avenues in the research and treatment of this condition.}, }
@article {pmid40001573, year = {2025}, author = {Mafe, AN and Büsselberg, D}, title = {Modulation of the Neuro-Cancer Connection by Metabolites of Gut Microbiota.}, journal = {Biomolecules}, volume = {15}, number = {2}, pages = {}, pmid = {40001573}, issn = {2218-273X}, support = {NPRP 14S0311-210033//QNRF/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; *Brain Neoplasms/metabolism/microbiology ; Dysbiosis/metabolism/microbiology ; Fatty Acids, Volatile/metabolism ; }, abstract = {The gut-brain-cancer axis represents a novel and intricate connection between the gut microbiota, neurobiology, and cancer progression. Recent advances have accentuated the significant role of gut microbiota metabolites in modulating systemic processes that influence both brain health and tumorigenesis. This paper explores the emerging concept of metabolite-mediated modulation within the gut-brain-cancer connection, focusing on key metabolites such as short-chain fatty acids (SCFAs), tryptophan derivatives, secondary bile acids, and lipopolysaccharides (LPS). While the gut microbiota's impact on immune regulation, neuroinflammation, and tumor development is well established, gaps remain in grasping how specific metabolites contribute to neuro-cancer interactions. We discuss novel metabolites with potential implications for neurobiology and cancer, such as indoles and polyamines, which have yet to be extensively studied. Furthermore, we review preclinical and clinical evidence linking gut dysbiosis, altered metabolite profiles, and brain tumors, showcasing limitations and research gaps, particularly in human longitudinal studies. Case studies investigating microbiota-based interventions, including dietary changes, fecal microbiota transplantation, and probiotics, demonstrate promise but also indicate hurdles in translating these findings to clinical cancer therapies. This paper concludes with a call for standardized multi-omics approaches and bi-directional research frameworks integrating microbiome, neuroscience, and oncology to develop personalized therapeutic strategies for neuro-cancer patients.}, }
@article {pmid40001396, year = {2025}, author = {Sher, AA and Whitehead-Tillery, CE and Peer, AM and Bell, JA and Vocelle, DB and Dippel, JT and Zhang, L and Mansfield, LS}, title = {Dynamic Spread of Antibiotic Resistance Determinants by Conjugation to a Human-Derived Gut Microbiota in a Transplanted Mouse Model.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {2}, pages = {}, pmid = {40001396}, issn = {2079-6382}, support = {RN031097-DEHN//Albert C. and Lois E. Dehn Chair Endowment/ ; NC1202//United States Department of Agriculture/ ; GS100019//University Distinguished Professor Endowment, Michigan State University/ ; U19AI090872//National Institutes of Health, Enterics Research Investigational Network, Cooperative Research Center/ ; Stipend to Azam A. Sher//College of Veterinary Medicine/ ; }, abstract = {BACKGROUND: Antibiotic-resistant (AR) bacteria pose an increasing threat to public health, but the dynamics of antibiotic resistance gene (ARG) spread in complex microbial communities are poorly understood. Conjugation is a predominant direct cell-to-cell mechanism for the horizontal gene transfer (HGT) of ARGs. We hypothesized that commensal Escherichia coli donor strains would mediate the conjugative transfer of ARGs to phylogenetically distinct bacteria without antibiotic selection pressure in gastrointestinal tracts of mice carrying a human-derived microbiota with undetectable levels of E. coli. Our objective was to identify a mouse model to study the factors regulating AR transfer by conjugation in the gut.<br><br>METHODS: Two donor E. coli strains were engineered to carry chromosomally encoded red fluorescent protein, and an ARG- and green fluorescent protein (GFP)-encoding broad host range RP4 conjugative plasmid. Mice were orally gavaged with two donor strains (1) E. coli MG1655 or (2) human-derived mouse-adapted E. coli LM715-1 and their colonization assessed by culture over time. Fluorescence-activated cell sorting (FACS) and 16S rDNA sequencing were performed to trace plasmid spread to the microbiota.<br><br>RESULTS: E. coli LM715-1 colonized mice for ten days, while E. coli MG1655 was not recovered after 72 h. Bacterial cells from fecal samples on days 1 and 3 post inoculation were sorted by FACS. Samples from mice given donor E. coli LM715-1 showed an increase in cells expressing green but not red fluorescence compared to pre-inoculation samples. 16S rRNA gene sequencing analysis of FACS GFP positive cells showed that bacterial families Lachnospiraceae, Clostridiaceae, Pseudomonadaceae, Rhodanobacteraceae, Erysipelotrichaceae, Oscillospiraceae, and Butyricicoccaceae were the primary recipients of the RP4 plasmid.<br><br>CONCLUSIONS: Results show this ARG-bearing conjugative RP4 plasmid spread to diverse human gut bacterial taxa within a live animal where they persisted. These fluorescent marker strategies and human-derived microbiota transplanted mice provided a tractable model for investigating the dynamic spread of ARGs within gut microbiota and could be applied rigorously to varied microbiotas to understand conditions facilitating their spread.}, }
@article {pmid40000989, year = {2025}, author = {Zhao, M and Zhang, Y and Liu, S and Wang, F and Zhang, P}, title = {Eradication of Helicobacter pylori reshapes gut microbiota and facilitates the evolution of antimicrobial resistance through gene transfer and genomic mutations in the gut.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {90}, pmid = {40000989}, issn = {1471-2180}, support = {32201393//National Natural Science Foundation of China/ ; }, mesh = {*Helicobacter pylori/drug effects/genetics ; Humans ; *Gastrointestinal Microbiome/genetics/drug effects ; *Helicobacter Infections/microbiology/drug therapy ; *Gene Transfer, Horizontal ; *Drug Resistance, Bacterial/genetics ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Feces/microbiology ; Mutation ; Metagenomics ; Female ; Evolution, Molecular ; Male ; Bacteria/genetics/classification/drug effects ; Middle Aged ; Genome, Bacterial ; Adult ; Klebsiella/genetics/drug effects ; }, abstract = {Treating Helicobacter pylori (H. pylori) infection requires large quantities of antibiotics, thus dramatically promoting the enrichment and dissemination of antimicrobial resistance (AMR) in feces. However, the influence of H. pylori eradication on the AMR mobility and the gut microbiota evolution has yet to be thoroughly investigated. Here, a study involving 12 H. pylori-positive participants was conducted, and the pre- and post- eradication fecal samples were sequenced. Metagenomic analysis revealed that the eradication treatment drastically altered the gut microbiome, with the Escherichia and Klebsiella genera emerging as the predominant bacteria. Interestingly, the eradication treatment significantly increased the relative abundance and diversity of resistome and mobilome in gut microbiota. Eradication of H. pylori also enriched AMR genes (ARGs) conferring resistance to antibiotics not administered because of the co-location with other ARGs or mobile genetic elements (MGEs). Additionally, the Escherichia and Klebsiella genera were identified as the primary bacterial hosts of these highly transferable ARGs. Furthermore, the genomic variations associated with ARGs in Escherichia coli (E. coli) caused by the eradication treatment were profiled, including the parC, parE, and gyrA genes. These findings revealed that H. pylori eradication promoted the enrichment of ARGs and MGEs in the Escherichia and Klebsiella genera, and further facilitated bacterial evolution through the horizontal transfer of ARGs and genomic variations.}, }
@article {pmid39999537, year = {2025}, author = {Dhanasekaran, D and Venkatesan, M and Sabarathinam, S}, title = {Efficacy of microbiome-targeted interventions in obesity management- A comprehensive systematic review.}, journal = {Diabetes &amp; metabolic syndrome}, volume = {19}, number = {2}, pages = {103208}, doi = {10.1016/j.dsx.2025.103208}, pmid = {39999537}, issn = {1878-0334}, mesh = {Humans ; *Obesity/therapy/microbiology ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; *Fecal Microbiota Transplantation/methods ; *Obesity Management/methods ; Body Composition ; Prognosis ; Synbiotics/administration &amp; dosage ; }, abstract = {BACKGROUND: Obesity is a global health crisis linked to numerous chronic diseases. The gut microbiome plays a crucial role in human metabolism, and emerging evidence suggests that modulating the microbiome may offer novel therapeutic avenues for obesity management.<br><br>OBJECTIVE: This systematic review aimed to assess the efficacy and safety of microbiome-targeted interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, in improving body composition, metabolic parameters, and inflammatory markers in overweight and obese adults.<br><br>METHODS: A comprehensive search of PubMed, Scopus, and ScienceDirect was conducted to identify relevant studies published between 2005 and 2023. Included studies were assessed for methodological quality and risk of bias using the Cochrane Collaboration tool.<br><br>RESULTS: Body composition: Most studies demonstrated significant reductions in body weight, Body mass index, and body fat percentage.<br><br>METABOLIC PARAMETERS: Improvements were observed in lipid profiles (reduced cholesterol, triglycerides) and glucose metabolism (improved insulin sensitivity).<br><br>INFLAMMATORY MARKERS: Significant reductions were observed in inflammatory markers such as Interleukins (IL-6, IL-8) and C-reactive protein.<br><br>MICROBIAL COMPOSITION: Interventions generally led to shifts in microbial composition, with increases in beneficial bacteria such as Bifidobacterium and Lactobacillus.<br><br>ADVERSE EVENTS: Adverse events were generally minimal and limited.<br><br>CONCLUSION: This review provides strong evidence that microbiome-targeted interventions can effectively improve body composition, metabolic parameters, and inflammatory markers in individuals with obesity. Further research is needed to optimize intervention strategies, identify specific microbial targets, and translate these findings into effective clinical applications.}, }
@article {pmid39999013, year = {2025}, author = {Tashkent, Y and Choo, JM and Richard, A and Wang, Z and Calzadilla-Bertot, L and Vasil, E and Miller, S and Taylor, SL and Ivey, KL and Woodman, R and Adler, B and Ayonrinde, OT and Olynyk, JK and Beilin, LJ and Mori, TA and Wigg, AJ and Muller, KR and Adams, LA and Rogers, GB}, title = {Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {45}, number = {3}, pages = {e70032}, pmid = {39999013}, issn = {1478-3231}, support = {//Gastroenterological Society of Australia/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Adult ; Male ; Female ; Cross-Sectional Studies ; *Fatty Liver/microbiology/diagnostic imaging ; Magnetic Resonance Imaging ; Feces/microbiology ; Liver/diagnostic imaging/pathology ; }, abstract = {BACKGROUND AND AIMS: Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.<br><br>METHODS AND RESULTS: At age 27&#x2009;years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having 'no SLD' (VLFF &#x2264;&#x2009;3.55%), 76 (12.9%) with 'mild-moderate' SLD (VLFF: 3.56%-13.4%) and 24 (4.10%) with 'severe' SLD (VLFF >&#x2009;13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [p&#x2009;=&#x2009;0.015], Pielou evenness [p&#x2009;=&#x2009;0.001] and Shannon diversity [p&#x2009;=&#x2009;0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild-moderate (p&#x2009;=&#x2009;0.004) and severe SLD groups (p&#x2009;=&#x2009;0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (q&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.<br><br>TRIAL REGISTRATION: The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369).}, }
@article {pmid39998920, year = {2025}, author = {Lundgrin, EL and Hatipoglu, B}, title = {Trending Modalities in Type 2 Diabetes Prevention.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {110}, number = {Supplement_2}, pages = {S187-S192}, doi = {10.1210/clinem/dgaf040}, pmid = {39998920}, issn = {1945-7197}, support = {//This work was supported by the Deborah and Ronald Ratner Fund/ ; //Mary B. Lee Chair/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/prevention &amp; control ; *Prediabetic State/therapy ; Gastrointestinal Microbiome ; Hypoglycemic Agents/therapeutic use ; Life Style ; Incretins/therapeutic use ; Fecal Microbiota Transplantation ; Insulin Resistance ; }, abstract = {CONTEXT: Prediabetes now affects a substantial proportion of the population, marking a growing group of individuals at increased risk for the development of type 2 diabetes (T2D). Given the profound effect of T2D on an individual's morbidity and mortality, T2D prevention is of critical importance.<br><br>EVIDENCE ACQUISITION: We searched PubMed and Ovid MEDLINE databases for recent systematic reviews, meta-analyses, and original research articles pertaining to prediabetes and the prevention of T2D.<br><br>EVIDENCE SYNTHESIS: T2D prevention strategies have focused on intensive lifestyle modification as well as numerous medications that ultimately improve insulin resistance. Recently, a better understanding of the gut microbiome's role in diabetes progression has suggested a possible preventive role for fecal transplant. Finally, multiple incretin pharmaceutical agents have been developed that show promise in the prevention and treatment of T2D.<br><br>CONCLUSION: The number of novel ways to prevent T2D is rapidly growing. A thorough understanding of the indications, outcomes, and limitations of these new therapies is critical for all who care for individuals with diabetes.}, }
@article {pmid39998294, year = {2025}, author = {Wolfe, TM and Jo, J and Pinkham, NV and Garey, KW and Walk, ST}, title = {The impact of ibezapolstat and other Clostridioides difficile infection-relevant antibiotics on the microbiome of humanized mice.}, journal = {Antimicrobial agents and chemotherapy}, volume = {69}, number = {4}, pages = {e0160424}, pmid = {39998294}, issn = {1098-6596}, support = {R01AI139261//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; TL1 TR002318/TR/NCATS NIH HHS/United States ; R01 CA215784/CA/NCI NIH HHS/United States ; R01 AI139261/AI/NIAID NIH HHS/United States ; 5TL1TR002318-08//HHS | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; R01CA215784//HHS | NIH | National Cancer Institute (NCI)/ ; //Acurx Pharmaceuticals, Inc/ ; }, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology ; Mice ; *Clostridium Infections/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects/genetics ; Vancomycin/pharmacology ; Humans ; *Clostridioides difficile/drug effects/pathogenicity ; RNA, Ribosomal, 16S/genetics ; Metronidazole/pharmacology ; Fecal Microbiota Transplantation ; Fidaxomicin/pharmacology ; Feces/microbiology ; Purine Nucleosides ; }, abstract = {Ibezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for the treatment of Clostridioides difficile infection (CDI). Previous studies demonstrated that IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done. The purpose of this study was to compare microbiome changes associated with IBZ to other clinically used CDI antibiotics. Groups of germ-free (GF) mice received a fecal microbiota transplant from one of two healthy human donors and were subsequently exposed to either IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control). 16S rRNA encoding gene sequencing of temporally collected stool samples was used to compare the gut microbiome perturbations between treatment and no-drug control groups. Among the tested antibiotics, the most significant change in microbiome diversity was observed in MET-treated mice. Each antibiotic had a unique effect, but changes in alpha and beta diversities following FDX- and IBZ-treated groups were less pronounced than those observed in VAN- or MET-treated groups. By the end of therapy, both IBZ and FDZ increased the relative abundance of Bacteroidota (phylum), with IBZ additionally increasing the relative abundance of Actinomycetota (phylum). In microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity than VAN and MET. Notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies.}, }
@article {pmid39996827, year = {2025}, author = {Lu, D and Ma, X and Tao, K and Lei, H}, title = {Advancements in the Pathogenesis, Diagnosis, and Therapeutic Implications of Intestinal Bacteria.}, journal = {Current issues in molecular biology}, volume = {47}, number = {2}, pages = {}, pmid = {39996827}, issn = {1467-3045}, support = {2024AFB070//Hubei Natural Science Foundation/ ; 2023XHYN043//Science Foundation of Union Hospital/ ; 82403220//National Natural Science Foundation of China/ ; }, abstract = {Intestinal bacteria form one of the most complex microbial communities in the human body, playing a crucial role in maintaining host health and contributing to the development of various diseases. Here, we provide a comprehensive overview of the composition and function of intestinal bacteria, the factors affecting their homeostasis, and their association and mechanisms with a range of diseases (e.g., inflammatory bowel diseases, colorectal cancer, metabolic diseases). Additionally, their advanced potential in disease diagnosis and treatment is highlighted. Therapies, such as chemotherapy, radiotherapy, and immunotherapy, are significantly impacted by intestinal bacteria, with research indicating that bacteria can enhance chemoimmunotherapy efficiency by affecting T cell recruitment and immune cell infiltration. Fecal microbiota transplantation has emerged as a promising option for treating recurrent Clostridium difficile infections and certain metabolic and neurological disorders. Gut bacteria-related serum metabolites serve as non-invasive indicators for diagnosing CRC, while fecal immunochemical tests offer promising applications in CRC screening. Future research is needed to better understand the causal relationships between intestinal bacteria and diseases, develop more precise diagnostic tools, and evaluate the effectiveness and safety of microbiome-targeted therapies in clinical treatment. This study provides deeper insights into the role of intestinal bacteria in human health and disease, providing a scientific basis for innovative therapeutic strategies that have the potential to transform the landscape of healthcare.}, }
@article {pmid39996473, year = {2025}, author = {Wang, X and Hu, M and Wu, W and Lou, X and Gao, R and Ma, T and Dheen, ST and Cheng, J and Xiong, J and Chen, X and Wang, J}, title = {Indole derivatives ameliorated the methamphetamine-induced depression and anxiety via aryl hydrocarbon receptor along "microbiota-brain" axis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2470386}, pmid = {39996473}, issn = {1949-0984}, mesh = {Animals ; *Receptors, Aryl Hydrocarbon/metabolism/genetics ; *Anxiety/chemically induced/drug therapy/metabolism ; Mice ; *Depression/chemically induced/drug therapy/metabolism/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Methamphetamine/adverse effects ; *Indoles/pharmacology ; Male ; Humans ; Mice, Inbred C57BL ; *Brain/metabolism/drug effects ; Tryptophan/metabolism ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; }, abstract = {In addition to the high neurotoxicity, depression, and anxiety are the most prominent characteristics of methamphetamine (Meth) withdrawal. Studies to date on the issue of Meth-associated depression and anxiety are focused on the brain, however, whether peripheral homeostasis, especially the "microbiota-gut" axis participates in these adverse outcomes, remains poorly understood. In the current study, with the fecal microbiota transplantation (FMT) assay, the mice received microbiota from Meth withdrawal mice displayed marked depression and anxiety behaviors. The 16S rRNA sequencing results showed that Meth withdrawal contributed to a striking reduction of Akkermansia, Bacteroides, Faecalibaculum, Desulfovibrio, and Anaerostipes, which are known to be associated with tryptophan (TRP) metabolism. Noteworthily, the substantial decreases of the indole derivatives from the TRP metabolic pathway, including IAA, IPA, ILA, IET, IArA, IAld, and TRM were observed in the serum of both Meth abusing humans and mice during Meth withdrawal with the UHPLC-MS/MS analysis. Combining the high and low TRP diet mouse model, the mice with high TRP diet obviously impeded Meth-associated depression and anxiety behaviors, and these results were further strengthened by the evidence that administration of IPA, IAA, and indole dramatically ameliorated the Meth induced aberrant behaviors. Importantly, these protective effects were remarkably counteracted in aryl hydrocarbon receptor knockout (AhR KO) mice, underlining the key roles of microbiota-indoles-AhR signaling in Meth-associated depression and anxiety. Collectively, the important contribution of the present work is that we provide the first evidence that peripheral gut homeostasis disturbance but not limited to the brain, plays a key role in driving the Meth-induced depression and anxiety in the periods of withdrawal, especially the microbiota and the indole metabolic disturbance. Therefore, targeting AhR may provide novel insight into the therapeutic strategies for Meth-associated psychological disorders.}, }
@article {pmid39996135, year = {2025}, author = {Sehgal, K and Berry, P and Cho, J and Saffouri, G and Dierkhising, RA and Battaglioli, E and Kashyap, PC and Pardi, D and Khanna, S}, title = {Body mass index changes after fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251321121}, pmid = {39996135}, issn = {1756-283X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a successful therapy for Clostridioides difficile infection (CDI). FMT from overweight donors is speculated to influence the recipient's body mass index (BMI) after administration for CDI.<br><br>OBJECTIVES: We investigated changes in the recipient's BMI after FMT in relation to the donor's BMI.<br><br>DESIGN: We conducted a retrospective cohort study involving patients who underwent FMT for recurrent CDI at Mayo Clinic between 2012 and 2019.<br><br>METHODS: We analyzed demographic and donor data for patients undergoing FMT at Mayo Clinic (2012-2019). Recipient BMI (pre- and post-FMT) and donor BMI were extracted from medical records. Mixed-effects linear regression was used to evaluate the impact of donor BMI, donor BMI category, recipient baseline BMI, time before and after FMT, and interactions between these variables on overall BMI change and BMI change per month. Kaplan-Meier curves were used to assess BMI changes (&#x2a7e;5&#x2009;units) based on the last recorded post-FMT BMI.<br><br>RESULTS: We analyzed data from 401 patients with recorded BMI measurements before and after FMT. The median age of the recipients at the time of FMT was 59.1&#x2009;years (interquartile range (IQR): 40.5-70.1&#x2009;years), with 61.6% being female. The median BMI for recipients prior to FMT was 26.7&#x2009;kg/m&#xb2; (IQR: 22.7-31.6&#x2009;kg/m&#xb2;), while the median BMI of the donors was 24.5&#x2009;kg/m[2] (IQR: 23.9-27.5&#x2009;kg/m[2]). Stool from donors with a normal BMI was used for 58.2% of recipients, while 41.8% received stool from pre-obese donors. Donor BMI data were missing for 3.2% of recipients. Donor BMI was not significantly associated with changes in recipient BMI; for each 1-unit increase in donor BMI, a 0.01-unit monthly increase was observed (95% confidence interval: -0.0003, 0.02; p&#x2009;=&#x2009;0.11). The log-rank test for BMI increases (&#x2a7e;+5) and decreases (&#x2a7d;-5) revealed no significant differences among the donor BMI groups (Chi-squared&#x2009;=&#x2009;4.4, p&#x2009;=&#x2009;0.1 for increases, Chi-squared&#x2009;=&#x2009;2, p&#x2009;=&#x2009;0.4 for decreases).<br><br>CONCLUSION: The lack of impact of donor BMI on BMI changes post-FMT suggests that these changes are more dependent on the recipient's metabolic profile. Prospective, controlled trials are required to analyze these results more comprehensively.}, }
@article {pmid39996003, year = {2025}, author = {Ren, K and Yong, C and Jin, Y and Rong, S and Xue, K and Cao, B and Wei, H}, title = {Unraveling the microbial mysteries: gut microbiota's role in ulcerative colitis.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1519974}, pmid = {39996003}, issn = {2296-861X}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. Recent research has highlighted the significant role of gut microbiota in the pathogenesis and treatment of UC. This review aims to provide a comprehensive overview of the current understanding of the relationship between gut microbiota and UC. We discuss the involvement of gut microbiota in the onset of UC, including the dysbiosis observed in patients and its potential mechanisms. Additionally, the role of extra-intestinal microbiota in UC pathogenesis is explored, which has been less studied but is gaining attention. The influence of gut microbiota on the efficacy of biological immunotherapy for UC is also examined, highlighting how microbial composition can influence treatment outcomes. Furthermore, we review microbiota transplantation, and their potential benefits in UC management. Finally, we consider the combined use of antibiotics and biological agents in UC treatment, discussing their synergistic effects and potential drawbacks. This review underscores the importance of gut microbiota in UC and suggests that targeting microbial communities could offer new avenues for effective treatment.}, }
@article {pmid39995913, year = {2025}, author = {Morshedbak, M and Rahimi, K and Tabandeh, MR}, title = {Effect of fecal microbiota transplantation on ulcerative colitis model in rats: The gut-brain axis.}, journal = {Heliyon}, volume = {11}, number = {3}, pages = {e42430}, pmid = {39995913}, issn = {2405-8440}, abstract = {STUDY OBJECTIVES: The impact of fecal microbiota transplantation (FMT) on the TLR4/MYD88/NF-kB signaling pathway in the colon in the ulcerative colitis model, as well as the incidence of anxiety behaviors caused by the colitis model was investigated.<br><br>METHODS: Twenthy four ats were induced with ulcerative colitis using a 4&#xa0;% acetic acid solution administered intrarectally and were subsequently treated with prednisolone and FMT. The study examined several indicators, such as TLR4, MYD88, and NF-&#x3ba;B mRNA expression, along with oxidative stress factors. Additionally, it examined the relationship between anxiety-related behaviors and colitis and assessed the pro-inflammatory cytokines in the hippocampus.<br><br>RESULTS: FMT led to lower disease score index and improved colon tissue pathology findings. This was associated with reduced mRNA expression of TLR4, MYD88, and NF-&#x3ba;B, as well as lower levels of TOS, and higher levels of TAC, GSH, and GSSG in colon tissues. FMT was found to reduce anxiety in both the open field and elevated plus maze tests. Additionally, levels of IL-6 and TNF-a were decreased in the hippocampus.<br><br>CONCLUSIONS: FMT suppressed acetic acid-induced colitis by inhibiting the TLR4/MYD88/NF-kB signaling pathway. FMT reduced anxiety in open field and plus maze tests, and resulted in decreased levels of IL-6 and TNF-a in the hippocampus.}, }
@article {pmid39994836, year = {2025}, author = {Wan, J and Zhou, J and Wang, Z and Liu, D and Zhang, H and Xie, S and Wu, K}, title = {Epidemiology, pathogenesis, diagnosis, and treatment of inflammatory bowel disease: Insights from the past two years.}, journal = {Chinese medical journal}, volume = {138}, number = {7}, pages = {763-776}, pmid = {39994836}, issn = {2542-5641}, mesh = {Humans ; *Inflammatory Bowel Diseases/epidemiology/diagnosis/therapy ; }, abstract = {Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic inflammation of the gastrointestinal tract with unknown etiology. The cause of IBD is widely considered multifactorial, with prevailing hypotheses suggesting that the microbiome and various environmental factors contribute to inappropriate activation of the mucosal immune system in genetically susceptible individuals. Although the incidence of IBD has stabilized in Western countries, it is rapidly increasing in newly industrialized countries, particularly China, making IBD a global disease. Significant changes in multiple biomarkers before IBD diagnosis during the preclinical phase provide opportunities for earlier diagnosis and intervention. Advances in technology have driven the development of telemonitoring tools, such as home-testing kits for fecal calprotectin, serum cytokines, and therapeutic drug concentrations, as well as wearable devices for testing sweat cytokines and heart rate variability. These tools enable real-time disease activity assessment and timely treatment strategy adjustments. A wide range of novel drugs for IBD, including interleukin-23 inhibitors (mirikizumab, risankizumab, and guselkumab) and small-molecule drugs (etrasimod and upadacitinib), have been introduced in the past few years. Despite these advancements, approximately one-third of patients remain primary non-responders to the initial treatment, and half eventually lose response over time. Precision medicine integrating multi-omics data, advanced combination therapy, and complementary approaches, including stem cell transplantation, psychological therapies, neuromodulation, and gut microbiome modulation therapy, may offer solutions to break through the therapeutic ceiling.}, }
@article {pmid39994634, year = {2025}, author = {Almheiri, RT and Hajjar, B and Alkhaaldi, SMI and Rabeh, N and Aljoudi, S and Abd-Elrahman, KS and Hamdan, H}, title = {Beyond weight loss: exploring the neurological ramifications of altered gut microbiota post-bariatric surgery.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {223}, pmid = {39994634}, issn = {1479-5876}, mesh = {Humans ; *Bariatric Surgery ; *Gastrointestinal Microbiome ; *Weight Loss ; *Nervous System Diseases/microbiology ; Animals ; }, abstract = {This review discusses findings related to neurological disorders, gut microbiota, and bariatric surgery, focusing on neurotransmitters, neuroendocrine, the pathophysiology of bacteria contributing to disorders, and possible therapeutic interventions. Research on neurotransmitters suggests that their levels are heavily influenced by gut microbiota, which may link them to neurological disorders such as Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Depression, and Autism spectrum disorder. The pathophysiology of bacteria that reach and influence the central nervous system has been documented. Trends in microbiota are often observed in specific neurological disorders, with a prominence of pro-inflammatory bacteria and a reduction in anti-inflammatory types. Furthermore, bariatric surgery has been shown to alter microbiota profiles similar to those observed in neurological disorders. Therapeutic interventions, including fecal microbiota transplants and probiotics, have shown potential to alleviate neurological symptoms. We suggest a framework for future studies that integrates knowledge from diverse research areas, employs rigorous methodologies, and includes long-trial clinical control groups.}, }
@article {pmid39991465, year = {2025}, author = {Ahmadi, A and Kouhsari, E and Razavi, S and Mohamadzadeh, N and Besharat, S and Vakili, MA and Amiriani, T}, title = {Comparative analysis of dominant gut microbiota in Inflammatory Bowel Disease patients and healthy individuals: A case-control study.}, journal = {New microbes and new infections}, volume = {64}, number = {}, pages = {101567}, pmid = {39991465}, issn = {2052-2975}, abstract = {BACKGROUND: Chronic inflammation in the gut might be linked to microbiota dysbiosis.<br><br>OBJECTIVE: This study aimed to investigate alterations in the gut microbiota composition of adult IBD patients compared to healthy controls.<br><br>METHODS: This case-control study investigated the relationship between faecal microbiota composition and IBD in adults. Real-time qPCR analysis using bacterial 16S rRNA gene quantified the abundance of six key bacterial groups (Firmicutes, Lactobacillus spp., Bifidobacterium spp., Fusobacterium spp., Bacteroides fragilis, and Faecalibacterium prausnitzii) in faecal samples from 30 IBD patients (13 Crohn's disease, 17 ulcerative colitis) and 30 healthy controls. A correlation matrix was employed to assess relationships between these bacteria.<br><br>RESULTS: Real-time qPCR revealed significant differences (p-value <0.05) in the abundance of several bacterial groups between IBD patients and healthy controls. Firmicutes, Fusobacterium spp., and B. fragilis were significantly more abundant (p-value <0.05) in IBD patients compared to controls. Conversely, Lactobacillus spp. and F. prausnitzii were both significantly less abundant (p-value <0.05) in IBD patients. While some bacterial groups exhibited trends toward higher abundance in either CD or UC patients, these differences were not statistically significant (p-value >0.111). The correlation matrix analysis revealed specific co-occurrence patterns: Bacteroides showed a strong negative correlation with Prevotella, more abundant in healthy controls, suggesting a shift in dominance in IBD patients. Lactobacillus spp. and F. prausnitzii exhibited a positive correlation in healthy individuals, indicating their potential cooperative role in maintaining gut homeostasis.<br><br>CONCLUSION: This study identified significant alterations in gut microbiota composition in adult IBD patients compared to healthy controls, with notable differences in the abundance of specific bacterial groups. These findings suggest that gut microbiota dysbiosis may play a critical role in IBD pathogenesis. The identification of specific bacterial imbalances provides a foundation for developing microbiota-based therapies, such as probiotics, prebiotics, and fecal microbiota transplantation, as potential interventions for restoring microbial balance and mitigating disease progression. Further research is needed to translate these insights into targeted therapeutic strategies and to explore their effectiveness in clinical settings.}, }
@article {pmid39989875, year = {2025}, author = {Bednárik, DS and Földvári-Nagy, KC and Simon, V and Rancz, A and Gede, N and Veres, DS and Paraskevopoulos, P and Schnabel, T and Erőss, B and Hegyi, P and Lenti, K and Földvári-Nagy, L}, title = {Comparative effectiveness of different therapies for Clostridioides difficile infection in adults: a systematic review and network meta-analysis of randomized controlled trials.}, journal = {The Lancet regional health. Europe}, volume = {49}, number = {}, pages = {101151}, pmid = {39989875}, issn = {2666-7762}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea, with substantial morbidity and mortality. CDI is a severe and growing problem with numerous treatment options. We evaluated the effectiveness of all therapies in recurrent and non-recurrent infections and their prevention.<br><br>METHODS: This network meta-analysis and systematic review of randomized controlled trials (RCTs) compared all CDI therapies and preventions. We included RCTs published until 19 August 2024 and focused on adult population. We performed a systematic search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Inclusion criteria were patients: adults (>16) treated against CDI; study type: randomized controlled trial; outcome: cure rate, recurrence or effectiveness of prevention. Any publication not meeting all criteria was considered to be ineligible and excluded. We applied random-effects meta-analysis using frequentist methods. We reported our main results as odds&#xa0;ratios (as a symmetric effect size measure, OR) with 95% confidence interval (95% CI). We used the Cochrane risk-of-bias tool to assess the risk of bias. Our study protocol was preregistered in PROSPERO (CRD42022371210).<br><br>FINDINGS: We assessed 73 RCTs with 28 interventions, involving 27,959 patients (49.2% female) in five networks. Fecal microbiota transplantation (FMT) was the most effective treatment in terms of the cure rate overall (P-score: 0.9952) and in recurrent cases (P-score: 0.9836). In recurrent cases, fidaxomicin (P-score: 0.6734) showed significantly greater effectiveness than vancomycin (P-score: 0.3677) and tolevamer (P-score: 0.0365). For non-recurrent CDI treatments ridinilazole, fidaxomicin, FMT and nitazoxanide were equally effective. Ridinilazole (P-score: 0.7671) and fidaxomicin (P-score: 0.7627) emerged as the most effective in preventing recurrence. Probiotics were not effective in preventing CDI, since network meta-analyses did not show significant differences between probiotics and placebo. In probiotics' subgroups pairwise meta-analyses Lactobacillaceae proved to be significantly more effective in prevention than placebo. Oral and colonoscopic FMT administration methods were equally effective. The study-level aggregated risk of bias of the publications included ranged from low to high. We observed relevant heterogeneity among studies in therapeutic doses, treatment durations, and follow-up times.<br><br>INTERPRETATION: The superiority of FMT in the treatment of CDI highlights the potential for increased use of FMT in clinical settings. Further research on optimizing FMT protocols and exploring its long-term safety and efficacy in larger samples is needed. Our findings suggest that the preventive use of probiotics might be questioned.<br><br>FUNDING: None.}, }
@article {pmid39989768, year = {2025}, author = {Reddi Sree, R and Kalyan, M and Anand, N and Mani, S and Gorantla, VR and Sakharkar, MK and Song, BJ and Chidambaram, SB}, title = {Newer Therapeutic Approaches in Treating Alzheimer's Disease: A Comprehensive Review.}, journal = {ACS omega}, volume = {10}, number = {6}, pages = {5148-5171}, pmid = {39989768}, issn = {2470-1343}, abstract = {Alzheimer's disease (AD) is an aging-related irreversible neurodegenerative disease affecting mostly the elderly population. The main pathological features of AD are the extracellular Aβ plaques generated by APP cleavage through the amyloidogenic pathway, the intracellular neurofibrillary tangles (NFT) resulting from the hyperphosphorylated tau proteins, and cholinergic neurodegeneration. However, the actual causes of AD are unknown, but several studies suggest hereditary mutations in PSEN1 and -2, APOE4, APP, and the TAU genes are the major perpetrators. In order to understand the etiology and pathogenesis of AD, various hypotheses are proposed. These include the following hypotheses: amyloid accumulation, tauopathy, inflammation, oxidative stress, mitochondrial dysfunction, glutamate/excitotoxicity, cholinergic deficiency, and gut dysbiosis. Currently approved therapeutic interventions are donepezil, galantamine, and rivastigmine, which are cholinesterase inhibitors (ChEIs), and memantine, which is an N-methyl-d-aspartate (NMDA) antagonist. These treatment strategies focus on only symptomatic management of AD by attenuating symptoms but not regeneration of neurons or clearance of Aβ plaques and hyperphosphorylated Tau. This review focuses on the pathophysiology, novel therapeutic targets, and disease-altering treatments such as α-secretase modulators, active immunotherapy, passive immunotherapy, natural antioxidant products, nanomaterials, antiamyloid therapy, tau aggregation inhibitors, transplantation of fecal microbiota or stem cells, and microtubule stabilizers that are in clinical trials or still under investigation.}, }
@article {pmid39989751, year = {2025}, author = {Arantes, JA and Di Pietro, R and Ratté, M and Arroyo, LG and Leclère, M and Costa, MC}, title = {Changes in bacterial viability after preparation and storage of fecal microbiota transplantation solution using equine feces.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e18860}, pmid = {39989751}, issn = {2167-8359}, mesh = {Animals ; Horses/microbiology ; *Feces/microbiology ; *Fecal Microbiota Transplantation/methods/veterinary ; *Microbial Viability/drug effects ; Cryoprotective Agents/pharmacology ; Freezing ; Glycerol/pharmacology ; Oxygen ; Cryopreservation ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been used as a treatment option for horses (Equus caballus) with gastrointestinal diseases. Several preparation and conservation protocols to improve bacterial survival have been studied in other species.<br><br>METHODS: This study aimed to evaluate the impact of oxygen exposure and different protectant solutions on bacterial viability before and after freezing using horse feces. Fecal samples from 10 healthy horses were aliquoted and diluted in cryoprotectant solutions containing antioxidants (n = 40) or 10% glycerol (n = 40). Half of the aliquots from each dilution condition were prepared inside an anaerobic chamber, while the other half were prepared under ambient air conditions. Each sample was also analyzed fresh and after freezing at -20 &#xb0;C for 90 days. Bacterial viability was assessed using flow cytometry. A mixed linear model and the Friedman and Wilcoxon tests were used depending on data distribution.<br><br>RESULTS: Freeze-thawing decreased bacterial viability by 47% (mean &#xb1; SD: 51 &#xb1; 27% before, 27 &#xb1; 8% after; p < 0.001). Glycerol was superior to the cryoprotectant after freezing (32 &#xb1; 8% glycerol, 24 &#xb1; 8% cryoprotectant; p < 0.001). Oxygen exposure did not affect viability (p = 0.13). There was no statistical difference between protectant solutions in fresh samples (p = 0.16).<br><br>CONCLUSIONS: Fresh FMT solutions may be better for treating horses with dysbiosis, but if freezing cannot be avoided, glycerol should be used to dilute feces.}, }
@article {pmid39988618, year = {2025}, author = {Liang, Y and Du, M and Li, X and Gao, J and Li, Q and Li, H and Li, J and Gao, X and Cong, H and Huang, Y and Li, X and Wang, L and Cui, J and Gan, Y and Tu, H}, title = {Upregulation of Lactobacillus spp. in gut microbiota as a novel mechanism for environmental eustress-induced anti-pancreatic cancer effects.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2470372}, pmid = {39988618}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Animals ; Humans ; Mice ; Fecal Microbiota Transplantation ; Killer Cells, Natural/immunology ; *Lactobacillus/genetics/physiology ; *Pancreatic Neoplasms/therapy/microbiology/immunology ; *Carcinoma, Pancreatic Ductal/therapy/microbiology/immunology ; Probiotics/administration &amp; dosage ; Tumor Microenvironment ; Feces/microbiology ; Male ; Up-Regulation ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Female ; Cell Line, Tumor ; Limosilactobacillus reuteri/physiology ; }, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited effective treatment options. Emerging evidence links enriched environment (EE)-induced eustress to PDAC inhibition. However, the underlying mechanisms remain unclear. In this study, we explored the role of gut microbiota in PDAC-suppressive effects of EE. We demonstrated that depletion of gut microbiota with antibiotics abolished EE-induced tumor suppression, while fecal microbiota transplantation (FMT) from EE mice significantly inhibited tumor growth in both subcutaneous and orthotopic PDAC models housed in standard environment. 16S rRNA sequencing revealed that EE enhanced gut microbiota diversity and selectively enriched probiotic Lactobacillus, particularly L. reuteri. Treatment with L. reuteri significantly suppressed PDAC tumor growth and increased natural killer (NK) cell infiltration into the tumor microenvironment. Depletion of NK cells alleviated the anti-tumor effects of L. reuteri, underscoring the essential role of NK cell-mediated immunity in anti-tumor response. Clinical analysis of PDAC patients showed that higher fecal Lactobacillus abundance correlated with improved progression-free and overall survival, further supporting the therapeutic potential of L. reuteri in PDAC. Overall, this study identifies gut microbiota as a systemic regulator of PDAC under psychological stress. Supplementation of psychobiotic Lactobacillus may offer a novel therapeutic strategy for PDAC.}, }
@article {pmid39984137, year = {2025}, author = {Dai, J and Yang, J and Han, S and Li, N and Wang, S and Xia, S and Kim, HH and Jun, Y and Lee, S and Kitagawa, Y and Xie, F and Yang, L and Shen, S and Chen, L and Turner, DP and Hodin, RA and Martyn, JAJ and Mao, J and You, Z}, title = {Deficiency of intestinal alkaline phosphatase affects behavior and microglia activity in mice.}, journal = {Brain, behavior, and immunity}, volume = {126}, number = {}, pages = {297-310}, pmid = {39984137}, issn = {1090-2139}, support = {R61 NS133083/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Microglia/metabolism/physiology ; *Alkaline Phosphatase/metabolism/deficiency/genetics ; Gastrointestinal Microbiome/physiology ; Mice ; Mice, Knockout ; *Behavior, Animal/physiology ; Mice, Inbred C57BL ; Male ; Brain/metabolism ; Fecal Microbiota Transplantation ; Anxiety/metabolism ; Phagocytosis/physiology ; }, abstract = {The gut microbiota plays crucial roles in the development and functions of the central nervous system (CNS) as well as in modulation of neurobehavior in heath and disease. The gut brush border enzyme intestinal alkaline phosphatase (IAP) is an important positive regulator of gut microbial homeostasis. In mice, IAP is encoded by Akp3 gene, which is specifically expressed in the duodenum of the small intestine. IAP deficiency alters gut bacterial composition and gut barrier function. Decreased IAP activity has been observed in aging, gut inflammatory diseases, and metabolic disorders. We hypothesized that this enzyme could also play an important role in modulating neurobehavior. We performed deep sequencing of gut bacterial 16S rRNA and found that IAP deficiency changed gut microbiota composition at various taxonomic levels. Using targeted metabolomic analysis, we also found that IAP deficiency resulted in changes of gut bacteria-derived metabolites in serum and brain metabolism. Neurobehavioral analyses revealed that Akp3[-/-] (IAP knockout) mice had decreased basal nociception thresholds, increased anxiety-like behavior, and reduced locomotor activity. Furthermore, Akp3[-/-] mice had more pronounced brain microglial phagocytic activity, together with an increase in the activated microglia population. Fecal microbiota transplantation from wildtype to Akp3[-/-] mice partially improved neurobehavior and reduced brain microglial phagocytic activity in Akp3[-/-] mice. This study demonstrates that deficiency of the endogenous gut-derived host factor IAP induces behavioral phenotype changes (nociception; motor activity, and anxiety) and affects brain microglia activity. Changes in the gut microbiota induced by knocking down Akp3 contribute to behavioral changes, which is probably mediated by microglia activity modulated by the gut bacteria-derived metabolites.}, }
@article {pmid39983749, year = {2025}, author = {Davido, B and Merrick, B and Kuijper, E and Benech, N and Biehl, LM and Corcione, S and , }, title = {How can the gut microbiome be targeted to fight multidrug-resistant organisms?.}, journal = {The Lancet. Microbe}, volume = {}, number = {}, pages = {101063}, doi = {10.1016/j.lanmic.2024.101063}, pmid = {39983749}, issn = {2666-5247}, abstract = {The rise of antimicrobial resistance presents a challenge to public health, undermines the efficacy of antibiotics, and compromises the management of infectious diseases. Gut colonisation by multidrug-resistant organisms, such as multidrug-resistant Enterobacterales and vancomycin-resistant enterococci, is associated with increased morbidity and mortality rates, as well as health-care costs. Of late, the role of the gut microbiome in combating colonisation by multidrug-resistant organisms, which could precede invasive infection, has garnered interest. Innovative interventions, including faecal microbiota transplantation, probiotics, phage therapy, and bacterial consortia, represent potential preventive or therapeutic options to counteract colonisation by multidrug-resistant organisms. In this Personal View, we have synthesised the current findings on these interventions and elucidated their potential as solutions to the crisis of antimicrobial resistance.}, }
@article {pmid39981255, year = {2025}, author = {Yao, K and Zheng, L and Chen, W and Xie, Y and Liao, C and Zhou, T}, title = {Characteristics, pathogenic and therapeutic role of gut microbiota in immunoglobulin A nephropathy.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1438683}, pmid = {39981255}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Glomerulonephritis, IGA/therapy/microbiology/immunology/etiology ; Animals ; Fecal Microbiota Transplantation ; Immunoglobulin A/immunology ; Immunity, Mucosal ; }, abstract = {Immunoglobulin A nephropathy (IgAN) is the most prevalent glomerulonephritis in the world, and it is one of the leading causes of end-stage kidney disease. It is now believed that the pathogenesis of IgAN is the mesangial deposition of immune complex containing galactose-deficient IgA1, resulting in glomerular injury. Current treatments for IgAN include supportive care and immunosuppressive therapy. A growing number of studies found that the gut microbiota in IgAN was dysregulated. Gut microbiota may be involved in the development and progression of IgAN through three main aspects: destruction of intestinal barrier, changes in metabolites and abnormal mucosal immunity. Interestingly, therapies by modulating the gut microbiota, such as fecal microbiota transplantation, antibiotic treatment, probiotic treatment, Chinese herbal medicine Zhen Wu Tang treatment, gluten-free diet, and hydroxychloroquine treatment, can improve IgAN. In this review, the alteration of gut microbiota in IgAN, potential pathogenic roles of gut microbiota on IgAN and potential approaches to treat IgAN by modulating the gut microbiota are summarized.}, }
@article {pmid39979990, year = {2025}, author = {Xie, H and Zhang, H and Zhou, L and Chen, J and Yao, S and He, Q and Li, Z and Zhou, Z}, title = {Fecal microbiota transplantation promotes functional recovery in mice with spinal cord injury by modulating the spinal cord microenvironment.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {210}, pmid = {39979990}, issn = {1479-5876}, support = {202201010803//Science and Technology Project Foundation of Guangzhou City/ ; 2024A03J1068//Science and Technology Project Foundation of Guangzhou City/ ; }, mesh = {Animals ; *Spinal Cord Injuries/therapy/physiopathology/microbiology/pathology ; *Fecal Microbiota Transplantation ; *Recovery of Function ; *Spinal Cord/pathology/physiopathology ; Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Mice ; *Cellular Microenvironment ; Axons/pathology ; Inflammation/pathology ; Neurons/pathology ; RNA, Ribosomal, 16S/genetics ; Nerve Regeneration ; Female ; Disease Models, Animal ; }, abstract = {BACKGROUND: spinal cord injury (SCI) disrupts the gut microbiota, worsening the injury's impact. Fecal microbiota transplantation (FMT) is increasingly recognized as a promising strategy to improve neural function post-SCI, yet its precise mechanisms are still far from clear. The present study aims to elucidate how FMT influences motor function recovery and its underlying mechanisms utilizing a SCI mouse model.<br><br>METHODS: Mice with SCI received FMT from healthy donors. We used 16&#xa0;S rRNA amplicon sequencing to analyze the alterations of gut microbes. Pathological alterations in the spinal cord tissue, including neuronal survival, axonal regeneration, cell proliferation, and neuroinflammation, were assessed among experimental groups. Additionally, RNA sequencing (RNA-seq) was used to explore alterations in relevant signaling pathways.<br><br>RESULTS: Significant shifts in gut microbiota composition following SCI were observed through 16&#xa0;S rRNA analysis. On day 7 post-SCI, the FMT group exhibited a significantly higher diversity of gut microbiota compared to the ABX group, with the composition in the FMT group more closely resembling that of healthy mice. FMT promoted neuronal survival and axonal regeneration, leading to notable improvements in motor function compared to control mice. Immunofluorescence staining showed increased neuronal survival, alleviated extracellular matrix (ECM) deposition, diminished glial scar formation, and reduced inflammation in FMT-treated mice. RNA-seq analysis indicated that FMT induced transcriptomic changes associated with material metabolism, ECM remodeling, and anti-inflammatory responses.<br><br>CONCLUSIONS: FMT restored gut microbiota balance in SCI mice, mitigated inflammation, and promoted ECM remodeling, establishing an optimal environment for neural recovery. These findings demonstrated that FMT may represent a valuable approach to enhance functional recovery following SCI.}, }
@article {pmid39979777, year = {2025}, author = {Nagy, M and Wychera, C and Schemm, J and Brewster, R and Duncan, CN}, title = {Bacterial and Parasitic Stool Studies Have Limited Utility in Pediatric Hematopoietic Stem Cell Transplant Patients.}, journal = {Pediatric blood &amp; cancer}, volume = {72}, number = {5}, pages = {e31617}, doi = {10.1002/pbc.31617}, pmid = {39979777}, issn = {1545-5017}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Child ; *Feces/parasitology/microbiology/virology ; Male ; Female ; Child, Preschool ; Adolescent ; *Graft vs Host Disease/etiology ; *Diarrhea/microbiology/etiology/parasitology/diagnosis ; Retrospective Studies ; Follow-Up Studies ; Infant ; *Bacteria/isolation &amp; purification ; Parasites/isolation &amp; purification ; Prognosis ; *Bacterial Infections/diagnosis/etiology/microbiology ; }, abstract = {BACKGROUND: Diarrhea is a common complication among pediatric hematopoietic stem cell transplantation (HCT) recipients. Although many of the cases are secondary to graft-versus-host disease (GVHD), stool microbiological studies are often performed to evaluate an underlying infectious etiology. The aim of this study was to assess the frequency and utility of stool studies in children who have undergone HCT.<br><br>METHODS: Demographics, clinical characteristics, and stool study results (viral, parasitic, and bacterial) of all patients who underwent HCT at a large, academic, freestanding children's hospital between January 2006 and December 2023 were obtained. Statistical analysis conducted included t tests, chi-square, and linear regression.<br><br>RESULTS: Overall, 1381 HCT recipients (9.2&#xa0;&#xb1;&#xa0;6.6 years) were included. Altogether, 6509 stool studies were obtained among 741 (54%) patients. Salmonella, Shigella, Yersinia, Campylobacter, and Escherichia coli (SSYCE) studies were sent on 363 (26%, 2252 studies) patients with 1 (0.04%) positive result. Clostridium difficile was sent on 706 (51%, 2055 studies) patients, with 156 positive studies (7.6%). Stool ova and parasite testing was sent on 143 (10%, 242 studies) patients, with two positive results (0.8%). Viral studies were sent on 638 (46%, 1960 studies) patients, with 107 positive studies (5.5%).<br><br>CONCLUSIONS: While testing for Clostridium difficile and enteric viruses may have value in the work-up of pediatric HCT patients, SSYCE and O&amp;P studies hold little to no value. Clinical practices surrounding routine stool microbiological studies should be reconsidered.}, }
@article {pmid39979287, year = {2025}, author = {Tsenkova, M and Brauer, M and Pozdeev, VI and Kasakin, M and Busi, SB and Schmoetten, M and Cheung, D and Meyers, M and Rodriguez, F and Gaigneaux, A and Koncina, E and Gilson, C and Schlicker, L and Herebian, D and Schmitz, M and de Nies, L and Mayatepek, E and Haan, S and de Beaufort, C and Cramer, T and Meiser, J and Linster, CL and Wilmes, P and Letellier, E}, title = {Ketogenic diet suppresses colorectal cancer through the gut microbiome long chain fatty acid stearate.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1792}, pmid = {39979287}, issn = {2041-1723}, support = {OT2 OD030544/OD/NIH HHS/United States ; U2C DK119886/DK/NIDDK NIH HHS/United States ; }, mesh = {*Diet, Ketogenic ; *Gastrointestinal Microbiome/physiology ; Animals ; *Stearic Acids/metabolism ; *Colorectal Neoplasms/diet therapy/microbiology/pathology/metabolism ; Humans ; Mice ; Male ; Apoptosis ; Female ; Bacteria/metabolism/genetics ; Disease Models, Animal ; Colon/microbiology/pathology ; Cell Line, Tumor ; Fecal Microbiota Transplantation ; }, abstract = {Colorectal cancer (CRC) patients have been shown to possess an altered gut microbiome. Diet is a well-established modulator of the microbiome, and thus, dietary interventions might have a beneficial effect on CRC. An attenuating effect of the ketogenic diet (KD) on CRC cell growth has been previously observed, however the role of the gut microbiome in driving this effect remains unknown. Here, we describe a reduced colonic tumor burden upon KD consumption in a CRC mouse model with a humanized microbiome. Importantly, we demonstrate a causal relationship through microbiome transplantation into germ-free mice, whereby alterations in the gut microbiota were maintained in the absence of continued selective pressure from the KD. Specifically, we identify a shift toward bacterial species that produce stearic acid in ketogenic conditions, whereas consumers were depleted, resulting in elevated levels of free stearate in the gut lumen. This microbial product demonstrates tumor-suppressing properties by inducing apoptosis in cancer cells and decreasing colonic Th17 immune cell populations. Taken together, the beneficial effects of the KD are mediated through alterations in the gut microbiome, including, among others, increased stearic acid production, which in turn significantly reduces intestinal tumor growth.}, }
@article {pmid39978693, year = {2025}, author = {Jiang, Y and Shi, L and Qu, Y and Ou, M and Du, Z and Zhou, Z and Zhou, H and Zhu, H}, title = {Multi-omics analysis reveals mechanisms of FMT in Enhancing antidepressant effects of SSRIs.}, journal = {Brain, behavior, and immunity}, volume = {126}, number = {}, pages = {176-188}, doi = {10.1016/j.bbi.2025.02.011}, pmid = {39978693}, issn = {1090-2139}, mesh = {Animals ; Male ; Mice ; Gastrointestinal Microbiome/drug effects/physiology ; Mice, Inbred C57BL ; *Depression/therapy/metabolism/drug therapy ; *Selective Serotonin Reuptake Inhibitors/pharmacology/therapeutic use ; Fluoxetine/pharmacology ; *Fecal Microbiota Transplantation/methods ; Antidepressive Agents/pharmacology ; Disease Models, Animal ; Hippocampus/metabolism ; Multiomics ; }, abstract = {OBJECTIVE: This study explores the behavioral and molecular biological impacts of Fecal Microbiota Transplantation (FMT) on depressive mice unresponsive to treatment with Selective Serotonin Reuptake Inhibitors (SSRIs).<br><br>METHODS: Healthy male C57BL/6 mice were used to establish a depression model through chronic restraint stress, treated with fluoxetine, and categorized into Response and Non-response groups. An FMT treatment was added to the Non-response group. Behavioral tests were conducted to assess symptoms of depression. The gut microbiome, plasma metabolites, and hippocampal tissue gene expression and function changes were analyzed using 16S rRNA gene sequencing, LC-MS, and RNA sequencing.<br><br>RESULTS: FMT significantly improved the depressive symptoms in SSRIs-resistant mice. There was a partial restoration in the diversity and structure of the gut microbiota in the FMT group. Compared to the Non-response group, significant changes were noted in the metabolomic profiles of the FMT group, identifying various differential metabolites. Functional annotations indicated that these metabolites are involved in multiple metabolic pathways. In the Non-response group, certain gene expression levels were significantly restored. GO and KEGG enrichment analyses revealed that these differential genes mainly involve cytokine activity, receptor signaling regulation, and NOD-like receptor signaling pathways. Joint analysis suggested that FMT may exert its effects through an increase in the abundance of g__Paraprevotella, leading to decreased baicalin content and increased Tal2 expression.<br><br>CONCLUSION: FMT has potential in improving depressive symptoms unresponsive to SSRIs treatment. Its mechanism may be related to the modulation of the gut microbiota and its metabolites, subsequently affecting gene expression.}, }
@article {pmid39978276, year = {2025}, author = {Luo, X and Cheng, P and Fang, Y and Wang, F and Mao, T and Shan, Y and Lu, Y and Wei, Z}, title = {Yinzhihuang formula modulates the microbe‒gut‒liver axis and bile acid excretion to attenuate cholestatic liver injury.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {139}, number = {}, pages = {156495}, doi = {10.1016/j.phymed.2025.156495}, pmid = {39978276}, issn = {1618-095X}, mesh = {Animals ; *Bile Acids and Salts/metabolism ; *Drugs, Chinese Herbal/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Male ; Mice ; Liver/drug effects/pathology/metabolism ; Mice, Inbred C57BL ; *Cholestasis, Intrahepatic/drug therapy/chemically induced ; Disease Models, Animal ; 1-Naphthylisothiocyanate ; Cholestasis/drug therapy ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Cholestatic liver injury is a hepatobiliary disorder primarily characterized by cholestasis, which significantly contributes to liver damage. The Yinzhihuang (YZH) oral preparation is an effective clinical treatment for cholestatic liver injury; however, the specific mechanism of action has not been clarified.<br><br>PURPOSE: This study investigated YZH's pharmacological mechanisms associated with the microbe&#x2012;gut&#x2012;liver axis in cholestatic mice, offering new perspectives for the treatment of cholestasis.<br><br>METHODS: YZH's protective effects were evaluated by evaluating serum liver injury indices and liver staining in an alpha-nephthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis mouse model. Colon hematoxylin&#x2012;eosin (H&amp;E) and alcian blue staining and FITC&#x2012;dextran leakage assays were performed to assess intestinal barrier integrity. Fluorescence in situ hybridization was employed to analyze bacterial translocation. Additionally, 16S rRNA sequencing, fecal microbiota transplantation, and bile acid metabolomics analysis were conducted to examine the relationships among the microbiome, bile acid metabolism, and YZH formula.<br><br>RESULTS: We found that YZH administration alleviated symptoms of ANIT-induced hepatic pathological injury and fibrosis. In addition, YZH reduced the transfer of gut bacteria to liver tissue by maintaining an intact intestinal barrier. Notably, YZH influenced the intestinal microbiota composition, upregulated the abundance of bile acid metabolism-associated probiotic bacteria, including Clostridiales, Lachnospiraceae and Bifidobacterium pseudolongum; and downregulated the abundance of Escherichia-Shigella and Serratia, thereby promoting bile acid excretion.<br><br>CONCLUSION: YZH protects against cholestatic liver damage by promoting bile excretion and maintaining intestinal mucosal barrier integrity. Furthermore, YZH alleviates cholestasis in a gut microbiota-dependent manner, and upregulation of probiotics may be crucial for YZH's influence on bile acid metabolism.}, }
@article {pmid39975140, year = {2025}, author = {Oppenheimer, M and Tao, J and Moidunny, S and Roy, S}, title = {Anxiety-like behavior during protracted morphine withdrawal is driven by gut microbial dysbiosis and attenuated with probiotic treatment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.01.29.633224}, pmid = {39975140}, issn = {2692-8205}, abstract = {The development of anxiety during protracted opioid withdrawal heightens the risk of relapse into the cycle of addiction. Understanding the mechanisms driving anxiety during opioid withdrawal could facilitate the development of therapeutics to prevent negative affect and promote continued abstinence. Our lab has previously established the gut microbiome as a driver of various side effects of opioid use, including analgesic tolerance and somatic withdrawal symptoms. We therefore hypothesized that the gut microbiome contributes to the development of anxiety-like behavior during protracted opioid withdrawal. In this study, we first established a mouse model of protracted morphine withdrawal, characterized by anxiety-like behavior and gut microbial dysbiosis. Next, we used fecal microbiota transplantation (FMT) to show that gut dysbiosis alone is sufficient to induce anxiety-like behavior. We further demonstrate that probiotic therapy during morphine withdrawal attenuates the onset of anxiety-like behavior, highlighting its therapeutic potential. Lastly, we examined transcriptional changes in the amygdala of morphine-withdrawn mice treated with probiotics to explore mechanisms by which the gut-brain axis mediates anxiety-like behavior. Our results support the use of probiotics as a promising therapeutic strategy to prevent gut dysbiosis and associated anxiety during opioid withdrawal, with potential implications for improving treatment outcomes in opioid recovery programs.}, }
@article {pmid39975029, year = {2025}, author = {Zhang, XS and Wang, Y and Sun, H and Zerbe, C and Falcone, E and Bhattacharya, S and Zhang, M and Gao, Z and Diaz-Rubio, ME and Bharj, D and Patel, D and Pan, S and Ro, G and Grenard, J and Armstrong, A and Yin, YS and Dominguez-Bello, MG and Holland, S and Su, X and Blaser, MJ}, title = {Gut microbiota phospholipids regulate intestinal gene expression and can counteract the effects of antibiotic treatment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39975029}, issn = {2692-8205}, abstract = {The gut microbiome influences immune and metabolic homeostasis. Our research using non-obese diabetic (NOD) mice revealed that early-life antibiotic exposure remodels the gut microbiome affecting metabolism and accelerating type 1 diabetes (T1D) incidence, with cecal material transplant (CMT) mitigating the damage. Now examining murine intestinal lipidomic profiles, we identified 747 compounds. Comparing the lipidomic profiles of cecal contents of conventional and germ-free mice and their diets, we identified 87 microbially-produced lipids reduced by antibiotic exposure but CMT-restored. Parallel analysis of human fecal lipid profiles after azithromycin-exposure showed significant alterations with substantial overlap with mice. In vitro co-culture with mouse macrophages or small intestinal epithelial cells and human colonic epithelial cells identified phospholipids that repress inflammation through the NFκB pathway. Oral administration of these phospholipids to antibiotic-treated NOD mice reduced expression of ileal genes involved in early stages of T1D pathogenesis. These findings indicate potential therapeutic anti-inflammatory roles of microbially-produced lipids.}, }
@article {pmid39974080, year = {2025}, author = {McCann, JR and Yang, C and Bihlmeyer, N and Tang, R and Truong, T and An, J and Jawahar, J and Ilkayeva, O and Muehlbauer, M and Hu, ZZ and Dressman, H and Poppe, L and Granek, J and David, LA and Shi, P and Balikcioglu, PG and Shah, S and Armstrong, SC and Newgard, CB and Seed, PC and Rawls, JF}, title = {Branched chain amino acid metabolism and microbiome in adolescents with obesity during weight loss therapy.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.02.03.25321363}, pmid = {39974080}, abstract = {BACKGROUND: Towards improving outcomes for adolescents with obesity, we aimed to define metabolic and microbiome phenotypes at baseline and post-weight loss intervention.<br><br>METHODS: The Pediatric Obesity Microbiome and Metabolism Study enrolled 220 adolescents aged 10-18 with severe obesity (OB) and 67 healthy weight controls (HWC). Blood, stool, and clinical measures were collected at baseline and after a 6-month intervention for the OB group. Serum metabolomic and fecal microbiome data were analyzed for associations with BMI, insulin resistance, and inflammation. Fecal microbiome transplants were performed on germ-free mice using samples from both groups to assess weight gain and metabolomic changes.<br><br>RESULTS: Adolescents with OB exhibited elevated serum branched-chain amino acids (BCAA) but reduced ketoacid metabolites (BCKA) compared to HWC. This pattern was sex- and age-dependent, unlike adults with OB, who showed elevated levels of both. The fecal microbiomes of adolescents with OB and HWC had similar diversity but differed in membership and functional potential. FMT from OB and HWC donors had similar effects on mouse body weight, with specific taxa linked to weight gain in FMT recipients. Longitudinal analysis identified metabolic and microbial features correlated with changes in health measures during the intervention.<br><br>CONCLUSION: Adolescents with OB have unique metabolomic adaptations and microbiome signatures compared to their HWC counterparts and adults with OB.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03139877 (Observational Study) and NCT02959034 (Repository).<br><br>FUNDING SOURCES: American Heart Association Grants: 17SFRN33670990, 20PRE35180195National Institute of Diabetes and Digestive and Kidney Diseases Grant: R24-DK110492.}, }
@article {pmid39973149, year = {2025}, author = {Zhang, T and Liu, S and Liu, S and Zhao, P and Zhang, C and Wang, X and Meng, Y and Lu, Y}, title = {Oleanolic Acid Alleviates Hyperuricemia via Gut Microbiota Control the Integrity of Gut Barrier and the Expressions of Urate Transporter in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {10}, pages = {5899-5914}, doi = {10.1021/acs.jafc.4c09270}, pmid = {39973149}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Oleanolic Acid/administration &amp; dosage ; *Hyperuricemia/metabolism/drug therapy/microbiology/genetics ; Mice ; Mice, Inbred C57BL ; Male ; Uric Acid/metabolism/blood ; *Organic Anion Transporters/metabolism/genetics ; Humans ; Kidney/metabolism/drug effects ; ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism/genetics ; Intestinal Mucosa/metabolism ; Glucose Transport Proteins, Facilitative/metabolism/genetics ; Fecal Microbiota Transplantation ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; }, abstract = {Hyperuricemia (HUA) is a globally prevalent metabolic disorder characterized by an imbalance in uric acid (UA) production and excretion. In this study, we found that oleanolic acid (OA), a natural pentacyclic triterpene, effectively reduced HUA and associated kidney injury in C57BL/6J mice. A 12-week OA treatment significantly and dose-dependently reduced UA and creatinine levels in serum and urine while suppressing hepatic xanthine oxidase activity in HUA mice. Mechanistic analysis revealed that OA modulates the expression of urate transporters including ABCG2, GLUT9, and URAT1 in the kidney and small intestine. Furthermore, OA restored gut microbiota imbalances, increased short-chain fatty acid production, and enhanced the expressions of intestinal tight junction proteins in HUA mice, thereby improving gut barrier integrity in HUA mice. Consequently, fecal microbiota transplantation (FMT) was employed to illustrate the major mediating role of gut microbiota in OA's alleviation of HUA in mice. Recipient HUA mice transplanted with feces from OA-treated HUA mice exhibited significantly lower blood and urinary UA levels, reduced kidney inflammation, and improved gut microbiota balance compared to those receiving feces from untreated HUA mice (p < 0.05). Additionally, FMT normalized urate transporter expression and reinforced intestinal tight junctions in recipient mice. These findings underscore that OA mitigates HUA primarily by modulating gut microbiota, regulating urate transporter expression, and reinforcing gut barrier integrity, offering novel insights into its preventive potential for managing HUA and related complications.}, }
@article {pmid39971913, year = {2025}, author = {Cune, D and Pitasi, CL and Rubiola, A and Jamma, T and Simula, L and Boucher, C and Fortun, A and Adoux, L and Letourneur, F and Saintpierre, B and Donnadieu, E and Terris, B and Bossard, P and Chassaing, B and Romagnolo, B}, title = {Inhibition of Atg7 in intestinal epithelial cells drives resistance against Citrobacter rodentium.}, journal = {Cell death &amp; disease}, volume = {16}, number = {1}, pages = {112}, pmid = {39971913}, issn = {2041-4889}, mesh = {Animals ; *Autophagy-Related Protein 7/metabolism/genetics/deficiency ; *Citrobacter rodentium/pathogenicity ; *Enterobacteriaceae Infections/microbiology/immunology/pathology ; Mice ; Gastrointestinal Microbiome ; Autophagy ; *Intestinal Mucosa/microbiology/metabolism/pathology ; *Epithelial Cells/metabolism/microbiology ; Colitis/microbiology/pathology/immunology ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Autophagy, a cytoprotective mechanism in intestinal epithelial cells, plays a crucial role in maintaining intestinal homeostasis. Beyond its cell-autonomous effects, the significance of autophagy in these cells is increasingly acknowledged in the dynamic interplay between the microbiota and the immune response. In the context of colon cancer, intestinal epithelium disruption of autophagy has been identified as a critical factor influencing tumor development. This disruption modulates the composition of the gut microbiota, eliciting an anti-tumoral immune response. Here, we report that Atg7 deficiency in intestinal epithelial cells shapes the intestinal microbiota leading to an associated limitation of colitis induced by Citrobacter rodentium infection. Mice with an inducible, intestinal epithelial-cell-specific deletion of the autophagy gene, Atg7, exhibited enhanced clearance of C. rodentium, mitigated hyperplasia, and reduced pathogen-induced goblet cell loss. This protective effect is linked to a higher proportion of neutrophils and phagocytic cells in the early phase of infection. At later stages, it is associated with the downregulation of pro-inflammatory pathways and an increase in Th17 and Treg responses-immune responses known for their protective roles against C. rodentium infection, modulated by specific gut microbiota. Fecal microbiota transplantation and antibiotic treatment approaches revealed that the Atg7-deficiency-shapped microbiota, especially Gram-positive bacteria, playing a central role in driving resistance to C. rodentium infection. In summary, our findings highlight that inhibiting autophagy in intestinal epithelial cells contributes to maintaining homeostasis and preventing detrimental intestinal inflammation through microbiota-mediated colonization resistance against C. rodentium. This underscores the central role played by autophagy in shaping the microbiota in promoting immune-mediated resistance against enteropathogens.}, }
@article {pmid39971742, year = {2025}, author = {Akagbosu, CO and McCauley, KE and Namasivayam, S and Romero-Soto, HN and O'Brien, W and Bacorn, M and Bohrnsen, E and Schwarz, B and Mistry, S and Burns, AS and Perez-Chaparro, PJ and Chen, Q and LaPoint, P and Patel, A and Krausfeldt, LE and Subramanian, P and Sellers, BA and Cheung, F and Apps, R and Douagi, I and Levy, S and Nadler, EP and Hourigan, SK}, title = {Gut microbiome shifts in adolescents after sleeve gastrectomy with increased oral-associated taxa and pro-inflammatory potential.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2467833}, pmid = {39971742}, issn = {1949-0984}, support = {R25 DK096944/DK/NIDDK NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome ; Adolescent ; Humans ; Animals ; Mice ; *Gastrectomy ; Feces/microbiology/chemistry ; Female ; Male ; *Bacteria/classification/isolation &amp; purification/genetics ; Bariatric Surgery ; Metabolome ; Th17 Cells/immunology ; T-Lymphocytes, Regulatory/immunology ; Pediatric Obesity/surgery/microbiology ; Leukocyte L1 Antigen Complex/analysis ; *Mouth/microbiology ; }, abstract = {Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown. Here, we show that adolescents exhibit significant gut microbiome and metabolome shifts several months after laparoscopic vertical sleeve gastrectomy (VSG), with increased alpha diversity and notably with enrichment of oral-associated taxa. To assess causality of the microbiome/metabolome changes in phenotype, pre-VSG and post-VSG stool was transplanted into germ-free mice. Post-VSG stool was not associated with any beneficial outcomes such as adiposity reduction compared pre-VSG stool. However, post-VSG stool exhibited a potentially inflammatory phenotype with increased intestinal Th17 and decreased regulatory T cells. Concomitantly, we found elevated fecal calprotectin and an enrichment of proinflammatory pathways in a subset of adolescents post-VSG. We show that in some adolescents, microbiome changes post-VSG may have inflammatory potential, which may be of importance considering the increased incidence of inflammatory bowel disease post-VSG.}, }
@article {pmid39969373, year = {2024}, author = {Li, Q and Obi, E and Marciniak, A and Newman, R and Whittle, I and Kufakwaro, J}, title = {Clinical and economic outcomes associated with fidaxomicin in comparison to vancomycin, metronidazole, and FMT: A systematic literature review.}, journal = {Medicine}, volume = {103}, number = {52}, pages = {e39219}, pmid = {39969373}, issn = {1536-5964}, mesh = {Humans ; *Fidaxomicin/therapeutic use/economics ; *Vancomycin/therapeutic use/economics ; *Metronidazole/therapeutic use/economics ; *Anti-Bacterial Agents/therapeutic use/economics ; *Clostridium Infections/therapy/drug therapy/economics ; *Fecal Microbiota Transplantation/economics/methods ; Cost-Benefit Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: There are an estimated half a million cases of Clostridioides difficile infection (CDI), in the United States annually. Fidaxomicin, vancomycin, and metronidazole are commonly used for CDI treatment, with fidaxomicin recommended by clinical guidelines as the preferred treatment for initial and recurrent CDI. This systematic literature review aimed to explore clinical and economic outcomes associated with fidaxomicin use with or without comparison to vancomycin, metronidazole, or fecal microbiota transplantation (FMT).<br><br>METHODS: The EMBASE, Medline, EconLit, and Evidence Based Medicine Reviews databases were searched from January 1st, 2012 to December 6th, 2022, as fidaxomicin was first approved for adult use in 2011. Identified publications were assessed and extracted by 2 independent reviewers.<br><br>RESULTS: Seventy-nine publications were included. Articles reporting at least 50 patients with follow-up &#x2264;90 days were selected to obtain comparable outcome definitions (N&#x2005;=&#x2005;14). Sustained clinical cure rate at 30- and 60-days follow-up was higher among fidaxomicin-treated patients (70.0-75.1% and 63.2-78.9%; N&#x2005;=&#x2005;3) than vancomycin (45.1-58.2% and 38.9-50.0%; N&#x2005;=&#x2005;3). Lower recurrence rates were reported post-fidaxomicin treatment compared to vancomycin, however the ranges overlapped at 30-, 60-, and 90-days follow-up. Limited outcomes for comparators metronidazole and FMT were identified. Healthcare resource use data were limited, with 2 studies reporting direct costs finding that fidaxomicin use-associated savings were driven by reduced hospital admission-related costs. Fidaxomicin was cost-effective in 14 of 21 economic analyses (11 vs vancomycin). Three studies reported vancomycin or FMT as more cost-effective than fidaxomicin. Fidaxomicin was consistently cost-effective or cost-saving among patients receiving concomitant antibiotics, and patients with cancer or renal impairment. Ten publications reported that the higher acquisition cost of fidaxomicin was offset by reduced recurrence and hospital readmission costs.<br><br>CONCLUSIONS: Fidaxomicin was clinically effective compared to vancomycin. Fidaxomicin is often reported as cost-effective, consistently within high-risk subpopulations.}, }
@article {pmid39968682, year = {2025}, author = {Yu, RL and Weber, HC}, title = {Irritable bowel syndrome, the gut microbiome, and diet.}, journal = {Current opinion in endocrinology, diabetes, and obesity}, volume = {32}, number = {3}, pages = {102-107}, doi = {10.1097/MED.0000000000000905}, pmid = {39968682}, issn = {1752-2978}, mesh = {Humans ; *Irritable Bowel Syndrome/microbiology/therapy/metabolism/diet therapy/physiopathology ; *Gastrointestinal Microbiome/physiology ; *Diet/adverse effects ; Fecal Microbiota Transplantation ; Brain-Gut Axis ; }, abstract = {PURPOSE OF REVIEW: To provide an update of recent studies exploring the role of the gut microbiota and diet in the pathogenesis and treatment of irritable bowel syndrome (IBS).<br><br>RECENT FINDINGS: The human gut microbiome has been recognized as an important, active source of signaling molecules that explain in part the disorder of the gut brain interaction (DGBI) in IBS. Subsequent changes in the metabolome such as the production of short-chain fatty acids (SCFA) and serotonin are associated with IBS symptoms. Dietary components are recognized as important triggers of IBS symptoms and a diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) has been shown effective and safe, even when used long-term. Fecal microbiota transplantation (FMT) in IBS has not shown sustained and effective IBS symptom reduction in controlled clinical trials.<br><br>SUMMARY: This update elucidates recent developments in IBS as it relates to clinical trial results targeting dietary and gut microbiota interventions. The gut microbiome is metabolically active and affects the bi-directional signaling of the gut-brain axis.}, }
@article {pmid39968343, year = {2025}, author = {Sun, T and Song, B and Li, B}, title = {Gut microbiota and atrial cardiomyopathy.}, journal = {Frontiers in cardiovascular medicine}, volume = {12}, number = {}, pages = {1541278}, pmid = {39968343}, issn = {2297-055X}, abstract = {Atrial cardiomyopathy is a multifaceted heart disease characterized by structural and functional abnormalities of the atria and is closely associated with atrial fibrillation and its complications. Its etiology involves a number of factors, including genetic, infectious, immunologic, and metabolic factors. Recent research has highlighted the critical role of the gut microbiota in the pathogenesis of atrial cardiomyopathy, and this is consistent with the gut-heart axis having major implications for cardiac health. The aim of this work is to bridge the knowledge gap regarding the interactions between the gut microbiota and atrial cardiomyopathy, with a particular focus on elucidating the mechanisms by which gut dysbiosis may induce atrial remodeling and dysfunction. This article provides an overview of the role of the gut microbiota in the pathogenesis of atrial cardiomyopathy, including changes in the composition of the gut microbiota and the effects of its metabolites. We also discuss how diet and exercise affect atrial cardiomyopathy by influencing the gut microbiota, as well as possible future therapeutic approaches targeting the gut-heart axis. A healthy gut microbiota can prevent disease, but ecological dysbiosis can lead to a variety of symptoms, including the induction of heart disease. We focus on the pathophysiological aspects of atrial cardiomyopathy, the impact of gut microbiota dysbiosis on atrial structure and function, and therapeutic strategies exploring modulation of the microbiota for the treatment of atrial cardiomyopathy. Finally, we discuss the role of gut microbiota in the treatment of atrial cardiomyopathy, including fecal microbiota transplantation and oral probiotics or prebiotics. Our study highlights the importance of gut microbiota homeostasis for cardiovascular health and suggests that targeted interventions on the gut microbiota may pave the way for innovative preventive and therapeutic strategies targeting atrial cardiomyopathy.}, }
@article {pmid39963784, year = {2025}, author = {Li, J and Jia, J and Teng, Y and Wang, X and Xia, X and Song, S and Zhu, B and Xia, X}, title = {Sea cucumber polysaccharides overcome immunotherapy resistance in tumor-bearing mice via modulation of the gut microbiome.}, journal = {Food &amp; function}, volume = {16}, number = {5}, pages = {2073-2083}, doi = {10.1039/d4fo05449k}, pmid = {39963784}, issn = {2042-650X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/pharmacology/administration &amp; dosage ; Mice ; *Sea Cucumbers/chemistry ; Immunotherapy ; *Colorectal Neoplasms/drug therapy/immunology/therapy ; Cell Line, Tumor ; Programmed Cell Death 1 Receptor/immunology ; Mice, Inbred BALB C ; Female ; Humans ; CD8-Positive T-Lymphocytes/immunology ; }, abstract = {Cancer immunotherapy has been successful in patients with different types of cancers, but its efficacy in treating certain types of colorectal cancer (CRC) is limited. The aim of this study was to explore whether sea cucumber polysaccharides (SCP) could impact resistance to anti-programmed cell death-1 (anti-PD1) immunotherapy of CRC and the role of microbiota in mediating their effects. Mice inoculated with immunotherapy resistant CT-26 CRC cells were pretreated with SCP, followed by treatment with/without the anti-PD1 antibody. SCP alone exhibited no inhibitory effect on tumor growth, but they drastically enhanced the efficacy of anti-PD1 treatment, which alone showed minimal effect on tumor development. Compared to anti-PD1 only treatment, a combination of SCP and anti-PD1 increased CD8[+] T cells, especially IFN-γ[+] cytotoxic CD8[+] T cells, and decreased regulatory CD4[+] T cells. SCP modulated gut microbiota and increased the relative abundance of bacteria including Bifidobacterium and Faecalibaculum. A fecal microbiota transplantation experiment showed that the sensitizing effect of SCP was at least partly mediated by microbiota. Furthermore, oral supplementation of Bifidobacterium pseudolongum or Faecalibaculum rodentium recapitulated the beneficial effect of SCP in potentiating anti-PD1 efficacy. Altogether, these findings demonstrated that SCP could be potentially developed as a dietary adjuvant to increase the efficacy of immunotherapy in CRC.}, }
@article {pmid39963663, year = {2025}, author = {Lin, DJ and Hu, DX and Wu, QT and Huang, LG and Lin, ZH and Xu, JT and He, XX and Wu, L}, title = {Analysis of influencing factors of washed microbiota transplantation in treating patients with metabolic syndrome.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1508381}, pmid = {39963663}, issn = {2296-861X}, abstract = {BACKGROUND AND AIMS: Metabolic Syndrome (MS) is a cluster of metabolic abnormalities closely associated with hypertension, diabetes, hyperlipidemia, obesity, etc. Our previous research indicated that fecal microbiota transplantation (FMT) could improve MS, but the factors influencing the efficacy of washed microbiota transplantation (WMT) in treating MS patients remain unclear. The objective of this study is to analyze the influencing factors of WMT in treating MS patients.<br><br>METHODS: The clinical data and influencing factors related to MS patients were collected retrospectively. Not only the changes in body mass index [BMI = weight (kg)/height (m)[2]], blood glucose, blood lipids, and blood pressure were analyzed, but also the influencing factors of WMT in treating MS patients were carried out based on Logistic Regression. The 16S rRNA gene amplicon sequencing was performed on fecal samples before and after WMT treatment.<br><br>RESULTS: A total of 210 patients were included, including 68 patients in the WMT group and 142 patients in the drug treatment (DT) group. WMT had a significant improvement and ASCVD downregulation effect on MS patients, and 42.65% of MS patients removed the label of MS after WMT treatment. Independent influencing factors for treating MS patients through WMT include age < 60 years old, high smoking index, infection, single donor selection, single-course WMT treatment, and having hypertension, diabetes, or obesity. WMT treated MS patients by maintaining the balance of gut microbiota.<br><br>CONCLUSIONS: WMT has a significant effect in improving MS and downregulating ASCVD risk stratification. The therapeutic effect of WMT on MS patients is closely related to their age, smoking index, infection, chronic disease status, donor type, and WMT courses. Therefore, we can improve the efficacy of WMT by reducing independent influencing factors that affect gut microbiota homeostasis.}, }
@article {pmid39962884, year = {2025}, author = {Marasco, G and Cannarile, DC and Cremon, C and Papalia, G and Marangoni, A and Zucchelli, A and Barone, M and Lazzarotto, T and Brigidi, P and Stanghellini, V and Barbara, G}, title = {Fecal microbiota transplantation for Clostridioides difficile infection in a peritoneal dialysis patient: A case report.}, journal = {Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis}, volume = {}, number = {}, pages = {8968608251316165}, doi = {10.1177/08968608251316165}, pmid = {39962884}, issn = {1718-4304}, abstract = {Chronic kidney disease (CKD) may be associated with dysbiosis which may increase the risk of gastrointestinal infections. Patients with kidney failure have a predominance of bacteria responsible for the exacerbation of chronic inflammation through the production of ureases, uricase, and uremic toxins and a reduction of bacteria-producing protective molecules as short-chain fatty acids. Patients with CKD have an increased risk of Clostridioides difficile infection. Currently, besides antibiotic therapy, fecal microbiota transplantation (FMT) is the only effective gut microbiota-targeted therapy for treating this infection. Scant evidence is available on FMT in those receiving peritoneal dialysis (PD). In this case, we report a successful FMT performed by colonoscopy in a patient receiving PD for polycystic kidney disease suffering from recurrent Clostridioides difficile infections. The FMT was repeated to enhance microbiota engraftment. The role of FMT in treating Clostridioides difficile in individuals receiving PD may be an important and promising therapeutic strategy but requires further prospective study.}, }
@article {pmid39961405, year = {2025}, author = {Wang, Z and Liu, T and Liu, L and Xie, J and Tang, F and Pi, Y and Zhong, Y and He, Z and Zhang, W and Zheng, C}, title = {Lactobacillus vaginalis alleviates DSS induced colitis by regulating the gut microbiota and increasing the production of 3-indoleacrylic acid.}, journal = {Pharmacological research}, volume = {213}, number = {}, pages = {107663}, doi = {10.1016/j.phrs.2025.107663}, pmid = {39961405}, issn = {1096-1186}, mesh = {Animals ; *Gastrointestinal Microbiome ; Dextran Sulfate ; *Probiotics/therapeutic use/pharmacology ; Mice, Inbred C57BL ; Mice ; *Indoles/metabolism ; *Colon/microbiology/metabolism/pathology/drug effects ; Fecal Microbiota Transplantation ; *Colitis, Ulcerative/chemically induced/microbiology/metabolism/therapy ; Disease Models, Animal ; *Colitis/chemically induced/microbiology ; Lactobacillus ; Feces/microbiology ; Intestinal Mucosa/metabolism/microbiology ; Female ; Male ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory disorder, and its incidence is experiencing an upward trend worldwide. UC can result in gut microbiota dysbiosis, impaired intestinal epithelial barrier, and systemic inflammation, for all of which there is presently no definitive treatment available. Lactobacillus is known to regulate gut microbiota and related metabolites to intervene in the development of UC. The objective of this study was to explore the underlying mechanism through which a novel probiotic, Lactobacillus vaginalis, alleviates DSS-induced colitis. Specifically, L. vaginalis were found to ameliorate the DSS-induced UC phenotype, restore intestinal microbiota balance and intestinal barrier function, and elevate the levels of 3-indoleacrylic acid (IAA) in mouse feces. Furthermore, fecal microbiota transplantation and fecal filtrate transplantation provide additional evidence that L. vaginalis alleviate DSS-induced colitis through metabolic products. Additionally, IAA has been shown to alleviate DSS-induced colitis symptoms, decrease inflammatory responses, and enhance intestinal barrier function. Finally, our findings confirm that L. vaginal and metabolites possess the capability to regulate the immune microenvironment in mice with colitis. And the RNA-seq analysis suggests that L. vaginal may play a pivotal role in alleviating colitis by modulating the PPAR signaling pathway. In conclusion, our findings suggest that oral administration of L. vaginalis alleviates DSS induced colonic inflammation by increasing the levels of IAA. L. vaginalis, as an emerging probiotic, provides a potential therapeutic strategy for clinical UC.}, }
@article {pmid39959619, year = {2025}, author = {Hao, J and Xu, H and Chang, B and Ren, J and Wang, H and Ji, L}, title = {Acupuncture mediates the "gut-testis axis" to improve asthenozoospermia.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1514010}, pmid = {39959619}, issn = {1664-2392}, mesh = {Male ; Animals ; *Asthenozoospermia/therapy/microbiology/pathology/metabolism ; *Acupuncture Therapy/methods ; Mice ; *Testis/metabolism/pathology ; *Gastrointestinal Microbiome/physiology ; Sperm Motility ; Spermatozoa ; Fecal Microbiota Transplantation ; Blood-Testis Barrier/metabolism ; }, abstract = {BACKGROUND: Asthenozoospermia is a common cause of male infertility. Studies have shown that sperm quality and motility are affected by the gut-testis axis that can regulate testicular metabolism and function through the gut microbiota and its metabolites. Acupuncture is an important modality of complementary and alternative medicine. It can improve sperm motility, but it remains unclear whether acupuncture can enhance sperm vitality by influencing the gut-testis axis.<br><br>METHODS: In this study, sperm quality, testicular pathology, and serum hormone levels were assessed using a cyclophosphamide-induced mouse model. Real-time PCR, a western blot analysis, and immunofluorescence techniques were used to assess the effects of acupuncture on the gut barrier and blood-testis barrier functions. In addition, gut microbiome and metabolomics were used to study the impact of acupuncture on the gut microbiota structure, serum, and testicular metabolites in asthenozoospermic mice. Further validation was obtained by performing a fecal microbiota transplantation (FMT).<br><br>RESULTS: Acupuncture improved the sperm quality; ameliorated testicular pathology; increased serum testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels; and repaired gut and blood-testis barrier damage in asthenozoospermic mice. The abundances of Bacteroidota, Firmicutes, Faecalibaculum, and Dubosiella were associated with sperm motility, as shown by a gut microbiome analysis. Serum metabolomics revealed that differentially expressed metabolites (DEMs), such as cytosine and N-oleyl-leucine, were closely related to sperm motility. Testicular metabolomics analysis revealed DEMs, such as 5-fluorouridine and 1-acetylimidazole, were also associated with sperm motility. Furthermore, reproductive function improvements in asthenozoospermic mice through acupuncture were achieved via an FMT.<br><br>CONCLUSION: Acupuncture may alleviate asthenozoospermia symptoms by modulating the gut-testis axis and repairing the gut-testis barrier.}, }
@article {pmid39958442, year = {2025}, author = {Ozbey, D and Saribas, S and Kocazeybek, B}, title = {Gut microbiota in Crohn's disease pathogenesis.}, journal = {World journal of gastroenterology}, volume = {31}, number = {6}, pages = {101266}, pmid = {39958442}, issn = {2219-2840}, mesh = {Humans ; *Crohn Disease/therapy/microbiology/immunology/pathology ; *Gastrointestinal Microbiome/immunology ; *Fecal Microbiota Transplantation/methods ; Intestinal Mucosa/microbiology/pathology/immunology ; Treatment Outcome ; Colon/microbiology/pathology/immunology ; Ileum/microbiology/pathology/immunology ; Dysbiosis/therapy ; }, abstract = {Inflammatory bowel diseases (IBDs) are classified into two distinct types based on the area and severity of inflammation: Crohn's disease (CD) and ulcerative colitis. In CD, gut bacteria can infiltrate mesenteric fat, causing expansion known as creeping fat, which may limit bacterial spread and inflammation but can promote fibrosis. The gut bacteria composition varies depending on whether the colon or ileum is affected. Fecal microbiota transplantation (FMT) transfers feces from a healthy donor to restore gut microbiota balance, often used in IBD patients to reduce inflammation and promote mucosal repair. The use of FMT for CD remains uncertain, with insufficient evidence to fully endorse it as a definitive treatment. While some studies suggest it may improve symptoms, questions about the duration of these improvements and the need for repeated treatments persist. There is a pressing need for methods that provide long-term benefits, as highlighted by Wu et al's research.}, }
@article {pmid39957504, year = {2025}, author = {Jiang, X and Zheng, Y and Sun, H and Dang, Y and Yin, M and Xiao, M and Wu, T}, title = {Fecal Microbiota Transplantation Improves Cognitive Function of a Mouse Model of Alzheimer's Disease.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {31}, number = {2}, pages = {e70259}, pmid = {39957504}, issn = {1755-5949}, support = {81971237//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Alzheimer Disease/therapy/psychology/pathology/genetics/complications ; Disease Models, Animal ; Mice ; Gastrointestinal Microbiome/physiology ; Mice, Transgenic ; Male ; Mice, Inbred C57BL ; *Cognition/physiology ; Amyloid beta-Peptides/metabolism ; Hippocampus/metabolism ; Maze Learning/physiology ; Amyloid Precursor Protein Secretases/metabolism ; }, abstract = {BACKGROUND: A growing body of evidence suggests a link between the gut microbiota and Alzheimer's disease (AD), although the underlying mechanisms remain elusive. This study aimed to investigate the impact of fecal microbiota transplantation (FMT) on cognitive function in a mouse model of AD.<br><br>METHODS: Four-month-old 5&#x2009;&#xd7;&#x2009;FAD (familial Alzheimer's disease) mice underwent antibiotic treatment to deplete their native gut microbiota. Subsequently, they received FMT either weekly or every other day. After 8&#x2009;weeks, cognitive function and &#x3b2;-amyloid (A&#x3b2;) load were assessed through behavioral testing and pathological analysis, respectively. The composition of the gut microbiota was analyzed using 16S rRNA sequencing.<br><br>RESULTS: Initial weekly FMT failed to alleviate memory deficits or reduce brain A&#x3b2; pathology in 5&#x2009;&#xd7;&#x2009;FAD mice. In contrast, FMT administered every other day effectively restored gut dysbiosis&#x2009;in 5&#x2009;&#xd7;&#x2009;FAD mice and decreased A&#x3b2; pathology and lipopolysaccharide levels in the colon and hippocampus. Mechanistically, FMT reduced the expression of amyloid &#x3b2; precursor protein, &#x3b2;-site APP cleaving enzyme 1, and presenilin-1, potentially by inhibiting the Toll-like receptor 4/inhibitor of kappa B kinase &#x3b2;/nuclear factor kappa-B signaling pathway. However, the cognitive benefits of FMT on 5&#x2009;&#xd7;&#x2009;FAD mice diminished over time.<br><br>CONCLUSION: These findings demonstrate the dose- and time-dependent efficacy of FMT in mitigating AD-like pathology, underscoring the potential of targeting the gut microbiota for AD treatment.}, }
@article {pmid39955611, year = {2025}, author = {Launspach, M and Mindermann, A and Schulz, J and Alasfar, L and Cyrull, S and Zirngibl, F and Oevermann, L and Künkele, A and Deubzer, HE and von Bernuth, H and Pruß, A and Lang, P and Bufler, P and Eggert, A and von Stackelberg, A and Schulte, JH}, title = {High Incidence and Impact of Suspected Exocrine Pancreatic Insufficiency in Patients Post-Hematopoietic Stem Cell Transplantation: A Single-Center Prospective Observational Study.}, journal = {United European gastroenterology journal}, volume = {13}, number = {2}, pages = {257-267}, pmid = {39955611}, issn = {2050-6414}, support = {//Charit&#xe9; - Universit&#xe4;tsmedizin Berlin &amp; the Berlin Institute of Health;/ ; }, mesh = {Humans ; *Exocrine Pancreatic Insufficiency/epidemiology/etiology/diagnosis ; Male ; Female ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Incidence ; Prospective Studies ; Risk Factors ; Child ; Adolescent ; Young Adult ; Pancreatic Elastase/analysis ; Feces/enzymology ; Child, Preschool ; Adult ; Ultrasonography ; }, abstract = {Exocrine pancreatic insufficiency (EPI) is suspected but remains understudied in immunosuppressed conditions such as post-hematopoietic stem cell transplantation (HSCT). This prospective observational study aimed to investigate the incidence, impact, and risk factors of EPI in a cohort of 83 pediatric and young adult patients who underwent allogeneic HSCT at Charité - Universitätsmedizin Berlin between 2020 and 2023. Fecal pancreatic elastase (PE) measurements and transabdominal ultrasound were utilized to evaluate pancreatic function over a one-year period. Secondary analysis explored the association of EPI with clinical complications and included a multivariable regression analysis of potential risk factors. Low PE levels significantly correlated with pathological pancreatic imaging findings, independent of concurrent diarrhea. EPI was suspected in 45% (32/71) of patients (95%CI: [34.1%, 56.6%]), with 29% (13/45) (95%CI: [17.7%, 43.4%]) showing signs of prolonged EPI (pEPI) lasting at least 8 weeks. After excluding cases with confounding factors such as missing enteral nutrition and diarrhea, the cumulative incidence of prolonged EPI was 20% (8/41) (95%CI: 10.2%-34.0%) in the overall cohort. EPI was associated with weight loss, prolonged dependence on parenteral nutrition, and extended hospitalizations. Adenovirus (ADV) infection emerged as a significant risk factor for EPI (hazard ratio 3.22 [95%CI:1.26-8.2], p = 0.014), along with additional factors such as higher BMI pre-HSCT, pre-existing pancreatic damage and early post-HSCT fasting. The persistence of pancreatic atrophy and EPI beyond two years post-HSCT in individual cases suggests a potential for permanent pancreatic damage. This study underscores that EPI is a common complication following HSCT, with ADV infection being an important risk factor. The findings support routine PE measurements and early initiation of pancreatic enzyme replacement therapy (PERT), alongside aggressive treatment of ADV infections. Further research is necessary to evaluate the effects of PERT in this population and to explore the applicability of these findings in other immunosuppressed groups.}, }
@article {pmid39947548, year = {2025}, author = {Ma, X and Liu, J and Jiang, L and Gao, Z and Shi, Z and Zhang, N and Wang, Z and Li, S and Zhang, R and Xu, S}, title = {Dynamic changes in the gut microbiota play a critical role in age-associated cognitive dysfunction via SCFAs and LPS synthesis metabolic pathways during brain aging.}, journal = {International journal of biological macromolecules}, volume = {304}, number = {Pt 2}, pages = {140945}, doi = {10.1016/j.ijbiomac.2025.140945}, pmid = {39947548}, issn = {1879-0003}, mesh = {*Gastrointestinal Microbiome ; Animals ; *Cognitive Dysfunction/microbiology/metabolism ; Mice ; *Fatty Acids, Volatile/metabolism/biosynthesis ; Humans ; *Aging/metabolism ; *Lipopolysaccharides/biosynthesis/metabolism ; Male ; *Brain/metabolism ; RNA, Ribosomal, 16S/genetics ; *Metabolic Networks and Pathways ; Aged ; Female ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Gut microbiota plays an essential role in cognitive dysfunction during aging. The aim of this study was to investigate the dynamic alterations in the gut microbiota and screen for key gut bacterial taxa correlated with age-associated cognitive dysfunction during natural aging.<br><br>METHODS: 16S rRNA gene sequencing was performed to determine the composition of the gut microbiota in faecal samples from SAMR1 and SAMP8 mice, cognitively normal controls (NC), and patients with amnestic mild cognitive impairment (aMCI). Faecal microbiota transplantation (FMT) and GMrepo database were used to screen key gut microbiota associated with cognitive decline in aging mice and humans.<br><br>RESULTS: The composition of the gut microbiota dynamically changed during natural aging in SAMR1 and SAMP8 mice, as well as in healthy subjects of different ages extracted from the GMrepo database. FMT from SAMR1 to SAMP8 mice altered the gut microbiota composition and improved the cognitive impairment in SAMP8 mice. Key gut bacterial taxa, including Lactobacillus, Akkermansia, Clostridium, Oscillospira and Dorea, were screened and validated to correlate with aging-associated cognitive decline. The function of the key gut bacterial taxa predicted by PICRUSt2 indicated that the metabolic pathways related to short-chain fatty acids (SCFAs) and lipopolysaccharide (LPS) synthesis were involved in age-associated cognitive dysfunction during natural aging.<br><br>CONCLUSION: These results demonstrate that the composition of the gut microbiota changes dynamically during brain aging, with some key gut bacterial taxa playing critical roles in age-associated cognitive dysfunction through SCFAs and LPS synthesis metabolic pathways.}, }
@article {pmid39946793, year = {2025}, author = {Chen, C and Xiao, Q and Wen, Z and Gong, F and Zhan, H and Liu, J and Li, H and Jiao, Y}, title = {Gut microbiome-derived indole-3-carboxaldehyde regulates stress vulnerability in chronic restraint stress by activating aryl hydrocarbon receptors.}, journal = {Pharmacological research}, volume = {213}, number = {}, pages = {107654}, doi = {10.1016/j.phrs.2025.107654}, pmid = {39946793}, issn = {1096-1186}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Receptors, Aryl Hydrocarbon/metabolism ; *Stress, Psychological/metabolism/microbiology ; Male ; Hippocampus/metabolism ; *Indoles/metabolism/pharmacology ; Restraint, Physical ; Rats, Sprague-Dawley ; Fecal Microbiota Transplantation ; Limosilactobacillus reuteri/metabolism ; Rats ; Colon/metabolism/microbiology ; Behavior, Animal/drug effects ; Neurogenesis ; Signal Transduction ; }, abstract = {Chronic stress constitutes a major precipitating factor for Major Depressive Disorder (MDD), and comprehending individual differences in stress responses is crucial for the development of effective intervention strategies for MDD. Recent studies indicate that an individual's vulnerability to chronic stress is closely associated with gut microbiota composition, but the underlying mechanisms remain unclear. This study aims to investigate whether the gut microbiota and its metabolites can serve as gut-brain signaling molecules and explores how the gut microbiota affects stress sensitivity. Here, we showed that gut microbiome-derived indole-3-carboxaldehyde (I3C) can act as a gut-brain signaling molecule that links tryptophan metabolism by gut microbes to stress vulnerability in the host. First, we identified a specific reduction in gut microbiome-derived I3C levels in the hippocampus and colon through untargeted and targeted metabolomic analyses. Then, the study of gut microbiota suggested that the relative abundance of lactobacillus was reduced significantly in stress-susceptible rats, whereas fecal microbiota transplantation regulates stress vulnerability. Furthermore, supplementation with I3C and the representative I3C-producing strain, Lactobacillus reuteri, was shown to alleviate depression-like behaviors induced by chronic stress. Further research confirms that I3C can inhibit neuroinflammation and promote hippocampal neurogenesis through the aryl hydrocarbon receptors (AhR) signal pathway, thereby mitigating the host's susceptibility to stress. In conclusion, our findings elucidate that the gut microbiome-derived-I3C can help buffer the host's stress through the AhR/SOCS2/NF-κB/NLRP3 pathway, providing a gut-brain signaling basis for emotional behavior.}, }
@article {pmid39946032, year = {2025}, author = {Karam, F and El Deghel, Y and Iratni, R and Dakroub, AH and Eid, AH}, title = {The Gut Microbiome and Colorectal Cancer: An Integrative Review of the Underlying Mechanisms.}, journal = {Cell biochemistry and biophysics}, volume = {}, number = {}, pages = {}, pmid = {39946032}, issn = {1559-0283}, abstract = {Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. While the incidence and mortality of CRC have decreased overall due to better screening, rates in adults under 50 have risen. CRC can manifest as inherited syndromes (10%), familial clustering (20%), or sporadic forms (70%). The gut microbiota, comprising mainly firmicutes and bacteroidetes, play a key role in CRC development and prevention. Indeed, CRC progression is influenced by the dynamic interaction between the gut microbiota, the intestinal barrier, the immune system, and the production of short-chain fatty acids. Not surprisingly, imbalance in the gut microbiota, termed dysbiosis, has been linked to CRC due to ensuing chronic inflammation, DNA damage, and oxidative stress. This may explain the notion that probiotics and fecal microbiota transplantation offer potential strategies for CRC prevention and treatment by restoring microbial balance and enhancing anti-cancer immune responses. This review appraises the roles of gut microbiota in promoting or preventing CRC. It also discusses the mechanistic interplay between microbiota composition, the intestinal barrier, and the immune system, with the hope of developing potential therapeutic strategies.}, }
@article {pmid39945558, year = {2025}, author = {Zhang, L and Liu, ZX and Liu, YH and Chen, Y and Chen, J and Lu, CH}, title = {Auricularia auriculaPolysaccharides Exert Anti-inflammatory Effects in Hepatic Fibrosis by the Gut-Liver Axis and Enhancing SCFA Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {8}, pages = {4617-4629}, pmid = {39945558}, issn = {1520-5118}, mesh = {Gastrointestinal Microbiome/drug effects ; Animals ; *Anti-Inflammatory Agents/administration &amp; dosage/chemistry ; *Liver/drug effects/metabolism/immunology ; Male ; Humans ; *Liver Cirrhosis/drug therapy/microbiology/immunology/metabolism/genetics ; *Auricularia/chemistry ; *Fatty Acids, Volatile/metabolism/immunology ; Mice ; *Polysaccharides/administration &amp; dosage ; NF-kappa B/immunology/genetics ; Bacteria/isolation &amp; purification/genetics/classification/metabolism ; Mice, Inbred C57BL ; Toll-Like Receptor 4/immunology/genetics ; }, abstract = {Auricularia auricula, esteemed in Chinese culture for their culinary and medicinal properties, exhibits notable metabolic and immunomodulatory effects. The principal active constituents are indigestible fermentable polysaccharides, which not only exhibit anti-inflammatory activities but also facilitate the proliferation of beneficial gut microbiota. However, the influence of gut-derived components on liver-regulated metabolic products remains insufficiently understood. This item offers insights into the therapeutic potential of wood ear mushrooms for treating hepatic fibrosis and the associated mechanisms. Following 8 weeks of treatment, a substantial reduction in ECM deposition was recorded, linked to modulation of the NLRP3 inflammasome activation. This study aims to reveal the potential microbiome-mediated mechanisms behind its therapeutic effects. Insights from antibiotic combination treatments indicate that the protective effects against ECM deposition rely on the presence of specific gut microbiota. This fecal microbiota intervention enhances key physiological mechanisms, underscoring the contributions of Lactobacillales, Rikenellaceae, and Bacteroidaceae in potentially mitigating fibrosis. Collectively, these findings suggest that interventions utilizing wood ear mushrooms may reduce inflammation and ECM deposition, mediated by the TLR4/NF-κB pathway.}, }
@article {pmid39944648, year = {2025}, author = {Lu, J and Jiang, M and Chai, D and Sun, Y and Wu, L}, title = {Integrative analysis of intestinal flora and untargeted metabolomics in attention-deficit/hyperactivity disorder.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1452423}, pmid = {39944648}, issn = {1664-302X}, abstract = {Attention Deficit Hyperactivity Disorder (ADHD) is a clinically common neurodevelopmental disorder of the brain. In addition to genetic factors, an imbalance in gut flora may also play a role in the development of ADHD. Currently, it is critical to investigate the function of gut flora and related metabolites, which may form the fundamental basis of bidirectional cross-linking between the brain and the gut, in addition to focusing on the changed gut flora in ADHD. This study aimed to investigate the possible relationship between changes in gut flora and metabolites and ADHD by analyzing metagenome and untargeted metabolomics of fecal samples from ADHD patients. Specifically, we attempted to identify key metabolites and the metabolic pathways they are involved in, as well as analyze in detail the structure and composition of the gut flora of ADHD patients. In order to further investigate the relationship between gut flora and ADHD symptoms, some behavioral studies were conducted following the transplantation of gut flora from ADHD patients into rats. The results of the metagenome analysis revealed several distinct strains, including Bacteroides cellulosilyticus, which could be important for diagnosing ADHD. Additionally, the ADHD group showed modifications in several metabolic pathways and metabolites, including the nicotinamide and nicotinic acid metabolic pathways and the metabolite nicotinamide in this pathway. The behavioral results demonstrated that rats with ADHD gut flora transplants displayed increased locomotor activity and interest, indicating that the onset of behaviors such as ADHD could be facilitated by the flora associated with ADHD. This research verified the alterations in gut flora and metabolism observed in ADHD patients and provided a list of metabolites and flora that were significantly altered in ADHD. Simultaneously, our findings revealed that modifications to the microbiome could potentially trigger behavioral changes in animals, providing an experimental basis for comprehending the function and influence of gut flora on ADHD. These results might provide new perspectives for the development of novel treatment strategies.}, }
@article {pmid39944265, year = {2024}, author = {Ye, ZN and Eslick, GD and Huang, SG and He, XX}, title = {Faecal microbiota transplantation for eradicating Helicobacter pylori infection: clinical practice and theoretical postulation.}, journal = {eGastroenterology}, volume = {2}, number = {4}, pages = {e100099}, pmid = {39944265}, issn = {2976-7296}, abstract = {The sustained increase in antibiotic resistance leads to a declining trend in the eradication rate of Helicobacter pylori (H. pylori) infection with antibiotic-based eradication regimens. Administration of a single probiotic shows limited efficacy in eradicating H. pylori infection. This review indicates that faecal microbiota transplantation (FMT), a novel therapeutic approach, either as a monotherapy or adjunctive therapy, exhibits beneficial effects in terms of the eradication of H. pylori infection and the prevention of adverse events. The role of FMT in H. pylori eradication may be associated directly or indirectly with some therapeutic constituents within the faecal suspension, including bacteria, viruses, antimicrobial peptides and metabolites. In addition, variations in donor selection, faecal suspension preparation and delivery methods are believed to be the main factors determining the effectiveness of FMT for the treatment of H. pylori infection. Future research should refine the operational procedures of FMT to achieve optimal efficacy for H. pylori infection and explore the mechanisms by which FMT acts against H. pylori.}, }
@article {pmid39943805, year = {2025}, author = {Ju, H and Zhou, Y and Wei, W and Hu, Y and Fang, H and Chen, Z and Sun, X and Shi, Y and Fang, H}, title = {Ageing-associated gut dysbiosis deteriorates mouse cognition.}, journal = {Acta biochimica et biophysica Sinica}, volume = {}, number = {}, pages = {}, doi = {10.3724/abbs.2024217}, pmid = {39943805}, issn = {1745-7270}, abstract = {Ageing is an independent factor for cognitive dysfunction. Ageing-associated alterations in the gut microbiota also affect cognition. The present study is designed to investigate changes in the gut microbiota and their participation in ageing-associated cognitive impairment. Both 10-week-old and 18-month-old mice are used. Mouse cognition is examined by novel object recognition and T-maze tests. Mouse feces are collected for sequencing and transplantation. Protein expression in the mouse intestine and hippocampus is studied using immunohistochemistry and immunofluorescence staining. Senescent neurons are induced by hydrogen peroxide in vitro. The cell lysates are used for western blot analysis and adenosine triphosphate (ATP) measurement. Our results show that 18-month-old mice exhibit cognitive dysfunction compared with young mice. In aged mice, transplanting the microbiota of young mice increases the protein presence of synaptophysin in the hippocampus and partially restores cognition. The protein expressions of mucin-2 and E-cadherin in the intestine are reduced in aged mice but are increased by transplantation. Gut microbiota analyses reveal that the reduced abundance of the microbe Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus in aged mice is restored by transplantation. Fecal microbiota transplantation in young mice increases the serum level of acetic acid in aged mice. Hydrogen peroxide stimulation induces senescence and reduces the protein expression levels of synaptophysin and acetyl-coenzyme A synthetase member 2 (ACSS2) in primary neurons. Incubation with acetic acid upregulates the protein expressions of ACSS2 and synaptophysin and further increases ATP production in senescent neurons. In summary, gut microbiota transplantation increases the abundance of Lactobacillales, elevates serum acetic acid level, and improves cognitive function in aged mice. Gut microbiota transplantation has therapeutic importance for ageing-associated cognitive decline.}, }
@article {pmid39941980, year = {2025}, author = {Li, J and Jia, J and Teng, Y and Wang, X and Xia, X and Song, S and Zhu, B and Xia, X}, title = {Polysaccharides from Sea Cucumber (Stichopus japonicus) Synergize with Anti-PD1 Immunotherapy to Reduce MC-38 Tumor Burden in Mice Through Shaping the Gut Microbiome.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {3}, pages = {}, pmid = {39941980}, issn = {2304-8158}, support = {Dljswgj202403//Dalian Jinshiwan Laboratory Project/ ; 81972692//National Natural Science of Foundation of China/ ; 2022YFD2100104//National Key Research and Development Program of China/ ; }, abstract = {Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and significantly improved outcomes for patients with certain malignancies. However, immunotherapy with ICIs is only effective in a subset of patients and the gut microbiota have been identified as an important factor associated with response to ICI therapy. Polysaccharides from sea cucumber (Stichopus japonicus) (SCP) have been shown to modulate the gut microbiota and exhibit beneficial health functions, but whether SCP could synergize with anti-PD1 immunotherapy remains unexplored. In this study, mice with ICI-sensitive MC38 tumors were treated with anti-PD1 antibody after supplementation with or without SCP to examine the potential impact of SCP on the efficacy of immunotherapy. SCP strongly amplified the anti-tumor activity of anti-PD1 in MC38 tumor-bearing mice. Flow cytometry and immunohistological staining demonstrated that SCP treatment increased cytotoxic CD8[+] T lymphocytes while decreasing regulatory Foxp3[+] CD4[+] T lymphocytes. Gut microbiota and metabolomic analysis revealed that SCP modulated the microbiota and increased the abundance of certain metabolites such as indole-3-carboxylic acid. Furthermore, fecal microbiota transplantation experiments justified that the synergistic effect of SCP with anti-PD1 was partially mediated through the gut microbiota. Mice receiving microbiota from SCP-treated mice showed a boosted response to anti-PD1, along with enhanced anti-tumor immunity. These findings indicate that SCP could be utilized as a dietary strategy combined with anti-PD1 therapy to achieve improved outcomes in patients.}, }
@article {pmid39939643, year = {2025}, author = {Tandoro, Y and Chiu, HF and Tan, CL and Hsieh, MH and Huang, YW and Yu, J and Wang, LS and Chan, CH and Wang, CK}, title = {Black raspberry supplementation on overweight and Helicobacter pylori infected mild dementia patients a pilot study.}, journal = {NPJ science of food}, volume = {9}, number = {1}, pages = {9}, pmid = {39939643}, issn = {2396-8370}, support = {R01 CA148818/CA/NCI NIH HHS/United States ; }, abstract = {Alzheimer's disease (AD) is the most common form of dementia. H. pylori infection and overweight have been implicated in AD via the gut-brain axis (GBA). This study aimed to determine whether supplementation of BRBs has a meaningful effect on H. pylori infection, overweight, and AD development in a clinical trial setting. We conducted a randomized placebo-controlled clinical trial in patients with mild clinical dementia who also had H. pylori infection and were overweight. The study was conducted over 10 weeks, consisting of an 8-week intervention period (25 g powder of black raspberries, BRBs, or placebo twice daily, morning and evening) and a 2-week follow-up. The primary outcomes were changes in Clinical Dementia Rating (CDR), Urea Breath Test (UBT), and Body Mass Index (BMI). Consumption of BRBs improved cognitive functions (p < 0.00001), compared to the placebo group (p > 0.05). Besides, BRBs ingestion decreased H. pylori infection and BMI (p < 0.00001 and p < 0.05 respectively) while the placebo group stayed statistically the same (p = 0.98 and p = 0.25 respectively). BRBs significantly decreased inflammatory markers, improved oxidative index, and adiponectin (p < 0.05) compared to the placebo group, while adenosine monophosphate-activated protein kinase (AMPK) and leptin did not significantly change. BRBs modulated the abundance of several fecal probiotics, particularly, Akkermansia muciniphila. Our results provided that BRBs suppressed H. pylori infection, decreased BMI, and rebalanced the gut microbiome, which could improve cognitive functions in mild dementia patients. Longer and larger randomized clinical trials of BRB interventions targeting H. pylori infection, overweight, or mild dementia are warranted to confirm the results from this pilot trial. Trial Registration: ClinicalTrials.gov identifier: NCT05680532.}, }
@article {pmid39938959, year = {2025}, author = {Støy, S and Eriksen, LL and Lauszus, JS and Damsholt, S and Baunwall, SMD and Erikstrup, C and Vilstrup, H and Jepsen, P and Hvas, C and Thomsen, KL}, title = {Cirrhosis and Faecal microbiota Transplantation (ChiFT) protocol: a Danish multicentre, randomised, placebo-controlled trial in patients with decompensated liver cirrhosis.}, journal = {BMJ open}, volume = {15}, number = {2}, pages = {e091078}, pmid = {39938959}, issn = {2044-6055}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Liver Cirrhosis/therapy/mortality ; Denmark ; Double-Blind Method ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Gastrointestinal Microbiome ; Male ; Treatment Outcome ; Female ; Disease Progression ; }, abstract = {INTRODUCTION: Liver cirrhosis is a progressive disease with high mortality. Gut microbiota derangement, increased gut permeability, bacterial translocation and chronic inflammation all drive disease progression. This trial aims to investigate whether faecal microbiota transplantation (FMT) may improve the disease course in patients with acute decompensation of liver cirrhosis.<br><br>METHODS AND ANALYSIS: In this Danish, multicentre, randomised, double-blinded, placebo-controlled trial, 220 patients with acute decompensation of liver cirrhosis and a Child-Pugh score&#x2264;12&#x2009;will be randomised (1:1) to oral, encapsulated FMT or placebo in addition to standard of care. Before the intervention, the patients will be examined and biological samples obtained, and this is repeated at 1 and 4 weeks and 3, 6 and 12 months after the intervention. The primary outcome is the time from randomisation to new decompensation or death. Secondary endpoints include mortality, number of decompensation events during follow-up and changes in disease severity and liver function.<br><br>ETHICS AND DISSEMINATION: The Central Denmark Region Research Ethics Committee approved the trial protocol (no. 1-10-72-302-20). The results will be published in an international peer-reviewed journal, and all patients will receive a summary of the results.<br><br>TRIAL REGISTRATION NUMBER: ClinicalTrials.gov study identifier NCT04932577.}, }
@article {pmid39935515, year = {2024}, author = {Yao, L and Zhou, X and Jiang, X and Chen, H and Li, Y and Xiong, X and Tang, Y and Zhang, H and Qiao, P}, title = {High-fat diet promotes gestational diabetes mellitus through modulating gut microbiota and bile acid metabolism.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1480446}, pmid = {39935515}, issn = {1664-302X}, abstract = {INTRODUCTION: Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance during pregnancy, estimated to affect approximately 20% of the whole pregnancies and is increasing in prevalence globally. However, there is still a big gap in knowledge about the association between gut microbiota associated metabolism alterations and GDM development.<br><br>METHODS: All the participants accomplished the validated internet-based dietary questionnaire for Chinese and serum, fecal samples were collected. HFD, control diet or colesevelam intervention was fed to GDM mice models or Fxr-/- mice models, with or without antibiotics cocktail treatment. Fecal microbiota transplantation were used for further validation. Gut microbiota and metabolites were detected by metagenomic sequencing and high-performance liquid chromatography-mass spectrometry, respectively. Bile acids of serum, fecal samples from human and mice were analysised. Body weight, average feed intake, blood glucose, insulin levels and oral glucose tolerance test was performed among each groups. Expression levels of Fxr, Shp and Fgf15 mRNA and protein were detected by quantitative reverse transcription polymerase chain reaction and western blot, respectively.<br><br>RESULTS: Our data indicated that high fat diet (HFD) was linked with higher prevalence of GDM, and HFD was positively associated with poor prognosis in GDM patients. Moreover, compared with normal diet (ND) group, GDM patients from HFD group performed a loss of gut microbiota diversity and enrichment of Alistipes onderdonkii, Lachnospiraceae bacterium 1_7_58FAA, and Clostridium aspaaragiforme while ruduction of Akkermansiaceae, Paraprevotell xylaniphila, and Prevotella copri. Additionally, HFD aggravated GDM in mice and gut microbiota depletion by antibiotics crippled the effect of excess fat intake. BAs profile altered in HFD GDM patients and mice models. Fecal microbiota transplantation (FMT) further confirmed that gut microbiota contributed to bile acids (BAs) metabolic dysfunction during HFD-associated GDM development. Mechanically, HFD-FMT administration activated Fxr, Shp, and Fgf15 activity, disturbed the glucose metabolism and aggravated insulin resistance but not in HFD-FMT Fxr-/- mice and ND-FMT Fxr-/- mice. Furthermore, colesevelam intervention alleviated HFD-associated GDM development, improved BAs metabolism, suppressed Fxr, Shp, and Fgf15 activity only in WT mice but not in the Fxr-/- HFD&#x202f;+&#x202f;Colesevelam group and Fxr-/- HFD group. HFD induced GDM and contributed to poor prognosis in GDM parturients through inducing gut microbial dysbiosis and metabolic alteration, especially appeared in BAs profile. Moreover, Fxr pathway participated in regulating HFD-associated gut microbiota disordered BAs metabolites and aggravating GDM in mice.<br><br>DISCUSSION: Modulating gut microbiota and BAs metabolites could be a potential therapeutic strategy in the prevention and treatment of HFD-associated GDM.}, }
@article {pmid39933444, year = {2025}, author = {Rob, M and Yousef, M and Lakshmanan, AP and Mahboob, A and Terranegra, A and Chaari, A}, title = {Microbial signatures and therapeutic strategies in neurodegenerative diseases.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {184}, number = {}, pages = {117905}, doi = {10.1016/j.biopha.2025.117905}, pmid = {39933444}, issn = {1950-6007}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/microbiology/therapy/metabolism ; Animals ; Dysbiosis ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Metabolome ; }, abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), arise from complex interactions between genetic factors, environmental exposures, and aging. Additionally, gut dysbiosis has been linked to systemic inflammation and neurodegeneration. Advances in microbiome and metabolome profiling techniques have provided deeper insights into how alterations in gut microbiota and dietary patterns affect metabolic pathways and contribute to the progression of NDs. This review explores the profiles of gut microbiome and metabolome derived biomarkers and their roles in NDs. Across phyla, families, and genera, we identified 55 microbial alterations in PD, 24 in AD, 4 in ALS, and 17 in MS. Some notable results include an increase in Akkermansia in PD, AD, and MS and a decrease in short-chain fatty acids (SCFAs) in PD and AD. We examined the effects of probiotics, prebiotics, fecal microbiota transplants (FMT), sleep, exercise, and diet on the microbiota, all of which contributed to delayed onset and alleviation of symptoms. Further, artificial intelligence (AI) and machine learning (ML) algorithms applied to omics data have been crucial in identifying novel therapeutic targets, diagnosing and predicting prognosis, and enabling personalized medicine using microbiota-modulating therapies in NDs patients.}, }
@article {pmid39933221, year = {2025}, author = {Cao, Y and Fan, X and Zang, T and Li, Y and Tu, Y and Wei, Y and Bai, J and Liu, Y}, title = {Gut microbiota causes depressive phenotype by modulating glycerophospholipid and sphingolipid metabolism via the gut-brain axis.}, journal = {Psychiatry research}, volume = {346}, number = {}, pages = {116392}, doi = {10.1016/j.psychres.2025.116392}, pmid = {39933221}, issn = {1872-7123}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Sphingolipids/metabolism ; Mice ; *Glycerophospholipids/metabolism ; Female ; *Depression/metabolism/microbiology ; *Brain/metabolism ; Humans ; Pregnancy ; Phenotype ; Fecal Microbiota Transplantation ; Lipid Metabolism ; Disease Models, Animal ; }, abstract = {Emerging evidence suggests that changes in the gut microbiota (GM) are related to prenatal depression onset, but the underlying molecular mechanisms remain obscure. This study was conducted to explore how disordered GM is involved in the onset of prenatal depression through the microbiome-gut-brain (MGB) axis. We transplanted fecal microbiota from women with and without prenatal depression into germ-free mice. Fecal metagenomic sequencing and LC-MS untargeted metabolomics analysis were performed to identify the GM composition, function, and metabolites in mice. Lipid metabolomics analysis was then used to characterize the lipid metabolism of brain tissue in mice. We found that mice transplanted with fecal microbiota from women with prenatal depression exhibited depressive-like behaviors as well as characteristic disorders of the phylum Firmicutes. Weighted Gene Correlation Network Analysis identified three microbial and one metabolic module in the gut, alongside two lipid metabolic modules in the brain, as significantly related to all depressive-like behaviors. These modules were enriched for glycerophospholipid and sphingolipid metabolism. In addition, the GM of mice with depressive-like behaviors were enriched and deficient in relevant functions and enzymes in the glycerophospholipid (mainly phosphatidylethanolamine) and sphingolipid (mainly hexosyl-ceramide) metabolic pathways, respectively. Consistently, glycerophospholipid and sphingolipid metabolites in the brains of depressive-like mice were up- and down-regulated. Increased phosphatidylethanolamine and decreased hexosyl-ceramide were significantly related to differential genera in the gut. Collectively, our findings provide a novel microbial and metabolic framework for understanding the role of the MGB axis in prenatal depression, indicating that the GM may be involved in the onset of depressive phenotypes by modulating central glycerophospholipid and sphingolipid metabolic homeostasis.}, }
@article {pmid39932857, year = {2025}, author = {Lopetuso, LR and Deleu, S and Puca, P and Abreu, MT and Armuzzi, A and Barbara, G and Caprioli, F and Chieng, S and Costello, SP and Damiani, A and Danese, S and Del Chierico, F and D'Haens, G and Dotan, I and Facciotti, F and Falony, G and Fantini, MC and Fiorino, G and Gionchetti, P and Godny, L and Hart, A and Kupčinskas, J and Iqbal, T and Laterza, L and Lombardini, L and Maharshak, N and Marasco, G and Masucci, L and Papa, A and Paramsothy, S and Petito, V and Piovani, D and Pugliese, D and Putignani, L and Raes, J and Ribaldone, DG and Sanguinetti, M and Savarino, EV and Sokol, H and Vetrano, S and Ianiro, G and Cammarota, G and Cominelli, F and Pizarro, TT and Tilg, H and Gasbarrini, A and Vermeire, S and Scaldaferri, F}, title = {Guidance for Fecal Microbiota Transplantation Trials in Ulcerative Colitis: The Second ROME Consensus Conference.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf013}, pmid = {39932857}, issn = {1536-4844}, support = {//European Crohn's and Colitis Organization/ ; //Crohn's &amp; Colitis Foundation: Clinical Research Investigator Initiated Award (CRIA)/ ; 882725//Senior Research Award (SRA)/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is emerging as a potential treatment modality for individuals living with inflammatory bowel disease (IBD). Despite its promise, the effectiveness of FMT for treating IBD, particularly for ulcerative colitis (UC), still requires thorough clinical investigation. Notwithstanding differences in methodologies, current studies demonstrate its potential for inducing remission in UC patients. Therefore, standardized and robust randomized clinical trials (RCTs) are needed to further support its efficacy for managing UC. The aim of the second Rome Consensus Conference was to address gaps and uncertainties identified in previous research regarding FMT and to offer a robust framework for future studies applied to the treatment of UC.<br><br>METHODS: Global experts in the field of clinical IBD, mucosal immunology, and microbiology (N&#x2005;=&#x2005;48) gathered to address the need for standardized clinical trials in FMT investigation. The group focused on key issues, such as stool donation, donor selection, characterization of fecal biomass, potential administration routes, as well as the process of induction, maintenance, and endpoint readouts.<br><br>RESULTS AND CONCLUSIONS: The consensus achieved during this conference established standardization of methods and protocols to enhance the current quality of research, with the aim of eventual implementation of FMT in managing UC and the ultimate goal of improving patient outcomes.}, }
@article {pmid39931541, year = {2025}, author = {Dong, S and Du, Y and Wang, H and Yuan, W and Ai, W and Liu, L}, title = {Research progress on the interaction between intestinal flora and microRNA in pelvic inflammatory diseases.}, journal = {Non-coding RNA research}, volume = {11}, number = {}, pages = {303-312}, pmid = {39931541}, issn = {2468-0540}, abstract = {Pelvic inflammatory disease (PID) is a common infectious disease of the female upper reproductive tract, and its pathological basis is immune inflammatory response. The imbalance of gut microflora (GM) may lead to the development of inflammatory process. A large number of studies have shown that fecal microbiota transplantation, probiotics, bacteria, prebiotics, and dietary intervention may play a potential role in remodeling GM and treating diseases. MicroRNAs (miRNAs) are involved in cell development, proliferation, apoptosis and other physiological processes. In addition, they play an important role in the inflammatory process, participating in the regulation of proinflammatory and anti-inflammatory pathways. Differences in miRNA profiles may be PID diagnostic tools and serve as prognostic markers of the disease. The relationship between miRNA and GM has not been fully elucidated. Recent studies have shown the role of miRNA in the regulation and induction of GM dysbiosis. In turn, microbiota can regulate the expression of miRNA and improve the immune status of the body. Therefore, this review aims to describe the interaction between GM and miRNA in PID, and to find potential precise targeted therapy for PID.}, }
@article {pmid39931312, year = {2025}, author = {Zhu, L and Yang, X}, title = {Gut Microecological Prescription: A Novel Approach to Regulating Intestinal Micro-Ecological Balance.}, journal = {International journal of general medicine}, volume = {18}, number = {}, pages = {603-626}, pmid = {39931312}, issn = {1178-7074}, abstract = {The intestinal microecology is comprises intestinal microorganisms and other components constituting the entire ecosystem, presenting characteristics of stability and dynamic balance. Current research reveals intestinal microecological imbalances are related to various diseases. However, fundamental research and clinical applications have not been effectively integrated. Considering the importance and complexity of regulating the intestinal microecological balance, this study provides an overview of the high-risk factors affecting intestinal microecology and detection methods. Moreover, it proposes the definition of intestinal microecological imbalance and the definition, formulation, and outcomes of gut microecological prescription to facilitate its application in clinical practice, thus promoting clinical research on intestinal microecology and improving the quality of life of the population.}, }
@article {pmid39931240, year = {2025}, author = {Wang, H and Li, S and Zhang, L and Zhang, N}, title = {Corrigendum: The role of fecal microbiota transplantation in type 2 diabetes mellitus treatment.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1555601}, doi = {10.3389/fendo.2025.1555601}, pmid = {39931240}, issn = {1664-2392}, abstract = {[This corrects the article DOI: 10.3389/fendo.2024.1469165.].}, }
@article {pmid39931170, year = {2025}, author = {Wang, H and Huang, W and Pan, X and Tian, M and Chen, J and Liu, X and Li, Q and Qi, J and Ye, Y and Gao, L}, title = {Quzhou Aurantii Fructus Flavonoids Ameliorate Inflammatory Responses, Intestinal Barrier Dysfunction in DSS-Induced Colitis by Modulating PI3K/AKT Signaling Pathway and Gut Microbiome.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {1855-1874}, pmid = {39931170}, issn = {1178-7031}, abstract = {PURPOSE: To explore the protective effect and underlying mechanism of Quzhou Aurantii Fructus flavonoids (QAFF) on Ulcerative colitis (UC).<br><br>METHODS: The constituents of QAFF were accurately determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The therapeutic impacts of QAFF were assessed in dextran sulfate sodium (DSS)-induced UC mice, focusing on the changes in body weight, disease activity index (DAI), colon length, histological assessment of colonic tissues, levels of pro-inflammatory cytokines, and expression of tight junction proteins. Western blotting confirmed key regulatory proteins within the differential signaling pathways, guided by transcriptome analysis. Additionally, the influence of QAFF on the gut microbiome was explored through 16S ribosomal RNA (rRNA) sequencing. The alterations in endogenous metabolites were detected by untargeted metabolomics, and their potential correlation with intestinal flora was then examined utilizing Spearman correlation analysis. Subsequently, the regulation of gut microbiome by QAFF was validated by fecal microbiota transplantation (FMT).<br><br>RESULTS: Eleven flavonoids, including Naringin and hesperidin, were initially identified from QAFF. In vivo experiments demonstrated that QAFF effectively ameliorated colitis symptoms, reduced IL-6, IL-1&#x3b2;, and TNF-&#x3b1; levels, enhanced intestinal barrier integrity, and downregulated PI3K/AKT pathway activation. Furthermore, QAFF elevated the levels of beneficial bacteria like Lachnospiraceae_NK4A136_group and Alloprevotella and concurrently reduced the pathogenic bacteria such as Escherichia-Shigella, [Eubacterium]_siraeum_group, and Parabacteroides. Metabolomics analysis revealed that 34 endogenous metabolites exhibited significant alterations, predominantly associated with Glycerophospholipid metabolism. These metabolites were significantly correlated with those differential bacteria modulated by QAFF. Lastly, the administration of QAFF via FMT ameliorated the colitis symptoms.<br><br>CONCLUSION: QAFF could ameliorate inflammatory responses and intestinal barrier dysfunction in DSS-induced UC mice probably by modulating the PI3K/AKT signaling pathway and gut microbiome, offering promising evidence for the therapeutic potential of QAFF in UC treatment.}, }
@article {pmid39930537, year = {2025}, author = {Liu, Q and Akhtar, M and Kong, N and Zhang, R and Liang, Y and Gu, Y and Yang, D and Nafady, AA and Shi, D and Ansari, AR and Abdel-Kafy, EM and Naqvi, SU and Liu, H}, title = {Early fecal microbiota transplantation continuously improves chicken growth performance by inhibiting age-related Lactobacillus decline in jejunum.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {49}, pmid = {39930537}, issn = {2049-2618}, support = {2017YFE0113700//National Key Research and Development Program of China/ ; HBZY2023B007//Supporting High Quality Development of Seed Industry Fund Project of Hubei Province/ ; }, mesh = {*Fecal Microbiota Transplantation/veterinary ; *Chickens/growth &amp; development/microbiology ; *Jejunum/microbiology ; *Lactobacillus/physiology ; Age Factors ; Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Body Weight ; Insulin-Like Growth Factor I/genetics/metabolism ; Growth Hormone/genetics/metabolism ; Gene Expression ; Gene Expression Profiling/veterinary ; Male ; Animals ; }, abstract = {BACKGROUND: At an early age, chickens commonly exhibit a rise in the average daily gain, which declines as they age. Further studies indicated that the decrease in chicken growth performance at a later age is closely associated with an age-related decline in Lactobacillus abundance in the small intestines. Whether inhibiting the age-related decline in Lactobacillus in the small intestine by early fecal microbiota transplantation (FMT) could improve chicken growth performance is an interesting question.<br><br>RESULTS: 16S rRNA gene sequencing revealed a higher jejunal Lactobacillus abundance in high body weight chickens in both two different chicken breeds (yellow feather chickens, H vs L, 85.96% vs 55.58%; white feather chickens, H vs L, 76.21% vs 31.47%), which is significantly and positively associated with body and breast/leg muscle weights (P&#x2009;<&#x2009;0.05). Moreover, the jejunal Lactobacillus abundance declined with age (30&#xa0;days, 74.04%; 60&#xa0;days, 50.80%; 120&#xa0;days, 34.03%) and the average daily gain rose in early age and declined in later age (1 to 30&#xa0;days, 5.78&#xa0;g; 30 to 60&#xa0;days, 9.86&#xa0;g; 60 to 90&#xa0;days, 7.70&#xa0;g; 90 to 120&#xa0;days, 3.20&#xa0;g), indicating the age-related decline in jejunal Lactobacillus abundance is closely related to chicken growth performance. Transplanting fecal microbiota from healthy donor chickens with better growth performance and higher Lactobacillus abundance to 1-day-old chicks continuously improved chicken growth performance (Con vs FMT; 30&#xa0;days, 288.45&#xa0;g vs 314.15&#xa0;g, P&#x2009;<&#x2009;0.05; 60&#xa0;days, 672.77&#xa0;g vs 758.15&#xa0;g, P&#x2009;<&#x2009;0.01; 90&#xa0;days, 1146.08&#xa0;g vs 1404.43&#xa0;g, P&#x2009;<&#x2009;0.0001) even after stopping fecal microbiota transplantation at 4th week. Four-week FMT significantly inhibited age-related decline in jejunal Lactobacillus abundance (Con vs FMT, 30&#xa0;days, 65.07% vs 85.68%, P&#x2009;<&#x2009;0.01; 60&#xa0;days, 38.87% vs 82.71%, P&#x2009;<&#x2009;0.0001 and 90&#xa0;days, 34.23% vs 60.86%, P&#x2009;<&#x2009;0.01). Moreover, the numbers of goblet and Paneth cells were also found significantly higher in FMT groups at three time points (P&#x2009;<&#x2009;0.05). Besides, FMT triggered GH/IGF-1 underlying signaling by significantly increasing the expressions of GH, GHR, and IGF-1 in the liver and IGF-1 and IGF-1R in muscles along age (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: These findings revealed that age-related decline in jejunal Lactobacillus abundance compromised chicken growth performance, while early fecal microbiota transplantation continuously improved chicken growth performance by inhibiting age-related jejunal Lactobacillus decline, promoting the integrity of jejunal mucosal barrier and up-regulating the expression level of genes related to growth axis. Video Abstract.}, }
@article {pmid39929593, year = {2025}, author = {Harigai, W and Mikami, K and Choudhury, ME and Yamauchi, H and Yajima, C and Shimizu, S and Miyaue, N and Nagai, M and Kubo, M and Tanaka, J and Katayama, T}, title = {Effects of fecal microbiota transplantation on behavioral abnormality in attention deficit hyperactivity disorder-like model rats.}, journal = {Journal of pharmacological sciences}, volume = {157}, number = {3}, pages = {189-198}, doi = {10.1016/j.jphs.2025.01.007}, pmid = {39929593}, issn = {1347-8648}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Attention Deficit Disorder with Hyperactivity/therapy/microbiology/psychology ; *Gastrointestinal Microbiome/genetics ; Disease Models, Animal ; Male ; *Behavior, Animal ; Rats, Sprague-Dawley ; Dysbiosis/therapy ; Rats ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. ADHD symptoms not only impact patients and their families but also impose societal costs. Current treatments for ADHD, including environmental adjustments and medication, are symptomatic and require long-term management. Recently, the link between gut microbiota dysbiosis and various psychiatric and neurological disorders has become evident. The effectiveness of fecal microbiota transplantation (FMT) from healthy individuals in treating autism spectrum disorder, a neurodevelopmental disorder related to ADHD, has been demonstrated. However, despite suggestions of a relationship between ADHD and gut microbiota, few studies have explored the efficacy of FMT for ADHD. In the current study, we used 16S rDNA analysis to show that ADHD-like model rats possess a gut microbiota that is distinct from that of healthy rats, and we demonstrated that FMT from healthy rats improved hyperactivity in ADHD-like model rats. Our findings suggest that differences in gut microbiota underlie ADHD-like behaviors and that FMT may be an effective treatment for ADHD.}, }
@article {pmid39926318, year = {2025}, author = {Rågård, N and Baumwall, SMD and Paaske, SE and Hansen, MM and Høyer, KL and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Validation methods for encapsulated faecal microbiota transplantation: a scoping review.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251314820}, pmid = {39926318}, issn = {1756-283X}, abstract = {Faecal microbiota transplantation (FMT) is increasingly used for diseases associated with a disrupted intestinal microbiome, mainly Clostridioides difficile infection. Encapsulated FMT is a patient-friendly application method that improves accessibility and convenience. Capsule processing may be standardised, but validation protocols are warranted. This review aimed to describe published validation methods for encapsulated FMT. Original studies reporting using encapsulated faecal formulations were included, regardless of indication. Studies were excluded if they did not address processing and validation or used non-donor-derived content. We conducted a comprehensive scoping review, implementing a systematic search strategy in PubMed, Embase and Web of Science. Processing data and validation methods were registered during full-text analysis and combined to create an overview of approaches for assessing quality in encapsulated FMT processing. The searches identified 324 unique studies, of which 44 were included for data extraction and analysis. We identified eight validation covariables: donor selection, pre-processing, preservation, oxygen-sparing processing, microbial count, viability, engraftment and clinical effect outcomes, from which we constructed a model for quality assessment of encapsulated FMT that exhaustively categorised processing details and validation measures. Our model comprised three domains: (1) Processing (donor selection and processing protocol), (2) Content analysis (microbiota measures and dose measures) and (3) Clinical effect (engraftment and clinical outcomes). No studies presented a reproducible capsule protocol; their validation strategies were sparse and divergent. The validation of FMT capsules is heterogeneous, and processing requires relevant standardisation protocols, mainly focusing on capsule content. Future studies should report validation covariables to enable accurate comparative assessments of clinical effects.}, }
@article {pmid39926224, year = {2025}, author = {Paul, JK and Azmal, M and Haque, ASNB and Meem, M and Talukder, OF and Ghosh, A}, title = {Unlocking the secrets of the human gut microbiota: Comprehensive review on its role in different diseases.}, journal = {World journal of gastroenterology}, volume = {31}, number = {5}, pages = {99913}, pmid = {39926224}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/physiology ; *Dysbiosis/microbiology/immunology/therapy ; Probiotics/therapeutic use/administration &amp; dosage ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; Neoplasms/microbiology/immunology ; Autoimmune Diseases/microbiology/immunology ; *Bacteria/pathogenicity/immunology ; Metabolic Diseases/microbiology/immunology ; }, abstract = {The human gut microbiota, a complex and diverse community of microorganisms, plays a crucial role in maintaining overall health by influencing various physiological processes, including digestion, immune function, and disease susceptibility. The balance between beneficial and harmful bacteria is essential for health, with dysbiosis - disruption of this balance - linked to numerous conditions such as metabolic disorders, autoimmune diseases, and cancers. This review highlights key genera such as Enterococcus, Ruminococcus, Bacteroides, Bifidobacterium, Escherichia coli, Akkermansia muciniphila, Firmicutes (including Clostridium and Lactobacillus), and Roseburia due to their well-established roles in immune regulation and metabolic processes, but other bacteria, including Clostridioides difficile, Salmonella, Helicobacter pylori, and Fusobacterium nucleatum, are also implicated in dysbiosis and various diseases. Pathogenic bacteria, including Escherichia coli and Bacteroides fragilis, contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues. The potential for microbiota-based therapies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, to improve health outcomes is examined. Future research directions in the integration of multi-omics, the impact of diet and lifestyle on microbiota composition, and advancing microbiota engineering techniques are also discussed. Understanding the gut microbiota's role in health and disease is essential for formulating personalized, efficacious treatments and preventive strategies, thereby enhancing health outcomes and progressing microbiome research.}, }
@article {pmid39924929, year = {2025}, author = {Zhong, H and Jiang, M and Yuan, K and Sheng, F and Xu, X and Cui, Y and Sun, X and Tan, W}, title = {Alterations in gut microbiota and metabolites contribute to postoperative sleep disturbances.}, journal = {Animal models and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ame2.12557}, pmid = {39924929}, issn = {2576-2095}, support = {82171187//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The composition of the intestinal flora and the resulting metabolites affect patients' sleep after surgery.<br><br>METHODS: We intended to elucidate the mechanisms by which disordered intestinal flora modulate the pathophysiology of postoperative sleep disturbances in hosts. In this study, we explored the impacts of anesthesia, surgery, and postoperative sleep duration on the fecal microbiota and metabolites of individuals classified postprocedurally as poor sleepers (PS) and good sleepers (GS), as diagnosed by the bispectral index. We also performed fecal microbiota transplantation in pseudo-germ-free (PGF) rats and applied Western blotting, immunohistochemistry, and gut permeability analyses to identify the potential mechanism of its effect.<br><br>RESULTS: Research finding shows the PS group had significantly higher postoperative stool levels of the metabolites tryptophan and kynurenine than the GS group. PGF rats that received gut microbiota from PSs exhibited less rapid eye movement (REM) sleep than those that received GS microbiota (GS-PGF: 11.4%&#x2009;&#xb1;&#x2009;1.6%, PS-PGF: 4.8%&#x2009;&#xb1;&#x2009;2.0%, p&#x2009;<&#x2009;0.001). Measurement of 5-hydroxytryptophan (5-HTP) levels in the stool, serum, and prefrontal cortex (PFC) indicated that altered 5-HTP levels, including reduced levels in the PFC, caused sleep loss in PGF rats transplanted with PS gut flora. Through the brain-gut axis, the inactivity of tryptophan hydroxylase 1 (TPH1) and TPH2 in the colon and PFC, respectively, caused a loss of REM sleep in PGF rats and decreased the 5-HTP level in the PFC.<br><br>CONCLUSIONS: These findings indicate that postoperative gut dysbiosis and defective 5-HTP metabolism may cause postoperative sleep disturbances. Clinicians and sleep researchers may gain new insights from this study.}, }
@article {pmid39924893, year = {2025}, author = {Chen, Y and Fang, H and Chen, H and Liu, X and Zhao, J and Stanton, C and Ross, RP and Chen, W and Yang, B}, title = {Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2464945}, pmid = {39924893}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Mice ; *Colorectal Neoplasms/microbiology/prevention &amp; control/pathology/metabolism ; Humans ; *Bifidobacterium/metabolism/physiology ; Linoleic Acids, Conjugated/metabolism ; Male ; Female ; *Fatty Acids/metabolism/chemistry ; Disease Models, Animal ; *Carcinogenesis ; Butyric Acid/metabolism ; Fecal Microbiota Transplantation ; Probiotics/administration &amp; dosage ; PPAR gamma/metabolism ; Mice, Inbred C57BL ; Bacteria/classification/metabolism/genetics/isolation &amp; purification ; }, abstract = {Colorectal cancer (CRC) represents the third most common cancer worldwide. Consequently, there is an urgent need to identify novel preventive and therapeutic strategies for CRC. This study aimed to screen for beneficial bacteria that have a preventive effect on CRC and to elucidate the potential mechanisms. Initially, we compared gut bacteria and bacterial metabolites of healthy volunteers and CRC patients, which demonstrated that intestinal conjugated linoleic acid (CLA), butyric acid, and Bifidobacterium in CRC patients were significantly lower than those in healthy volunteers, and these indicators were significantly negatively correlated with CRC. Next, spontaneous CRC mouse model were conducted to explore the effect of supplemental CLA-producing Bifidobacterium on CRC. Supplementation of mice with CLA-producing Bifidobacterium breve CCFM683 and B. pseudocatenulatum MY40C significantly prevented CRC. Moreover, molecular approaches demonstrated that CLA and the CLA-producing gene, bbi, were the key metabolites and genes for CCFM683 to prevent CRC. Inhibitor intervention results showed that PPAR-γ was the key receptor for preventing CRC. CCFM683 inhibited the NF-κB signaling pathway, up-regulated MUC2, Claudin-1, and ZO-1, and promoted tumor cell apoptosis via the CLA-PPAR-γ axis. Additionally, fecal microbiota transplantation (FMT) and metagenomic analysis showed that CCFM683 up-regulated Odoribacter splanchnicus through CLA production, which then prevented CRC by producing butyric acid, up-regulating TJ proteins, regulating cytokines, and regulating gut microbiota. These results will contribute to the clinical trials of Bifidobacterium and the theoretical research and development of CRC dietary products.}, }
@article {pmid39924042, year = {2025}, author = {Wu, T and Song, F and Huang, J and Cui, S and Wang, L and Yang, Q and Wu, Y and Li, B and Tu, Y and Wan, X and Liu, J}, title = {Gut microbiota: The pivotal conduit in the onset of constipation and its alleviation by tea flower polysaccharides (TFP) in a mouse model.}, journal = {International journal of biological macromolecules}, volume = {304}, number = {Pt 1}, pages = {140808}, doi = {10.1016/j.ijbiomac.2025.140808}, pmid = {39924042}, issn = {1879-0003}, mesh = {Animals ; *Constipation/drug therapy/microbiology/chemically induced ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/pharmacology/chemistry/therapeutic use ; Mice ; Disease Models, Animal ; *Flowers/chemistry ; Male ; *Tea/chemistry ; Fecal Microbiota Transplantation ; Gastrointestinal Transit/drug effects ; }, abstract = {Plant-derived bioactive components, such as polysaccharides, provide promising alleviating effects on constipation with minimal side-effects compared to pharmacological interventions. This study aimed to explore the therapeutic potential of tea flower polysaccharides (TFP) on constipation and the involved mechanisms. In a loperamide-induced constipation mouse model, TFP administration significantly increased fecal water content from 54.23-57.30 % to 63.70-79.36 %, enhanced intestinal transit rate from 30.80 % to 38.81 %, and reduced gastrointestinal (GI) transit time from 234.4 min to 186.2 min. TFP restored levels of both excitatory and inhibitory hormones related to GI motility. Transcriptomic analysis of colonic epithelial cells revealed that TFP restored expression of 544 genes involved in various pathways, including the NF-κB and JAK-STAT signaling pathways, which are associated with the improvement of constipation. Gut microbiota analysis demonstrated that TFP mitigated dysbiosis by normalizing the Firmicutes/Bacteroidota ratio, inhibiting pathogenic genera (e.g., Helicobacter), and promoting beneficial genera (e.g., Muribaculaceae, Bacteroides, Parabacteroides). The mediating role of gut microbiota in the onset of constipation and its alleviation was confirmed through fecal microbiota transplantation (FMT). Furthermore, TFP and its combination with anti-constipation drugs alleviated constipation-induced hepatorenal damage. This study highlights TFP's potential in treating constipation and underscores the essential role of gut microbiota in its therapeutic effects.}, }
@article {pmid39923429, year = {2025}, author = {Yang, F and Yan, Q and Wang, Y and Li, Q and Wang, J and Zeng, X and Pi, Y and Zhang, M and Wei, L}, title = {AMP1-1 alleviates bone loss in weightless rats by reducing peripheral 5-HT content via the microbiota-gut-bone axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {139}, number = {}, pages = {156447}, doi = {10.1016/j.phymed.2025.156447}, pmid = {39923429}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Rats ; Rats, Sprague-Dawley ; *Atractylodes/chemistry ; *Serotonin/metabolism ; Male ; *Polysaccharides/pharmacology ; X-Ray Microtomography ; Fecal Microbiota Transplantation ; Weightlessness/adverse effects ; Bone and Bones/drug effects/metabolism ; Osteogenesis/drug effects ; Bone Density/drug effects ; }, abstract = {BACKGROUND: Weightlessness-induced bone loss (WIBL) refers to the reduction of bone mass and the decline of bone resistance to load in a weightless environment. However, current treatment strategies aimed at increasing bone mass are associated with various limitations and side effects, highlighting the urgent need for safer and more effective therapeutic options to address WIBL.<br><br>PURPOSE: We aimed to further explore the potential mechanism of the anti-WIBL effect of Atractylodes macrocephalon polysaccharide1-1(AMP1-1). To find a better way to treat WIBL and provide new insights for the development of therapeutic drugs for this condition.<br><br>METHODS: Firstly, the anti-weightlessness bone loss of AMP1-1 was verified by micro-computed tomography (Micro-CT), three-point mechanical bending test and Western Blot (WB). Subsequently, the intestinal barrier was examined using histopathology, immunohistochemistry (IHC), and WB. Finally, validation experiments were performed using fecal microbiota transplantation (FMT). After FMT, 16S rDNA sequencing was used to analyze the gut microbiota composition in the rat feces.<br><br>RESULTS: AMP1-1 was able to inhibit WIBL by enhancing bone mass, improving toughness, and increasing osteogenic activity. Meanwhile, AMP1-1 reduced peripheral 5-HT content by restoring enterochromaffin cell function through gut microbiota regulation and tight junction repair. FMT of rat fecal microbiota after gavage of AMP1-1 into tail suspension rats still has the effects of regulating gut microbiota, repairing intestinal barrier and reducing bone loss.<br><br>CONCLUSION: Our results demonstrate that AMP1-1 exerts a protective effect against WIBL in rats, potentially by modulating 5-HT content and 5-HT-related metabolism in bone tissue through microbiota-gut-bone axis. This study is the first to elucidate the mechanism of AMP1-1 in mitigating WIBL through the perspective of the microbiota-gut-bone axis. Moreover, this research integrates plant extract research with the issue of bone loss induced by microgravity (aerospace medicine), thereby opening new avenues for natural drug research.}, }
@article {pmid39922394, year = {2025}, author = {Xu, W and Liu, A and Gong, Z and Xiao, W}, title = {L-theanine prevents ulcerative colitis by regulating the CD4+ T cell immune response through the gut microbiota and its metabolites.}, journal = {The Journal of nutritional biochemistry}, volume = {139}, number = {}, pages = {109845}, doi = {10.1016/j.jnutbio.2025.109845}, pmid = {39922394}, issn = {1873-4847}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/prevention &amp; control/immunology/microbiology/metabolism ; *Glutamates/pharmacology ; Animals ; Male ; *CD4-Positive T-Lymphocytes/immunology/drug effects ; Mice ; Dextran Sulfate ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Colon/pathology/drug effects/immunology ; }, abstract = {The disturbance of gut microbiota and its metabolites are considered to be the causes of ulcerative colitis (UC), which leads to immune abnormalities. Diet is the most important regulator of gut microbiota; therefore, it has a beneficial impact on UC. A novel food ingredient, l-theanine, alters the gut microbiota, thereby regulating gut immunity. However, whether l-theanine prevents UC by altering the gut microbiota, as well as the underlying mechanisms, remains unknown. Here, l-theanine was used to optimize the gut microbiota and its metabolites. Furthermore, to explore the mechanism by which l-theanine prevents UC, an l-theanine fecal microbiota solution was used to prevent dextran sulfate sodium-induced UC via fecal microbiota transplantation. Improvements in the colonic structure, colon histology scores, immune factors (IL-10), and inflammatory factors (IL-1β) demonstrated the preventive effect of l-theanine on UC. The 16S rDNA and metabolomic results showed that tryptophan-, short chain fatty acid-, and bile acid-related microbiota, such as Muribaculaceae, Lachnospiraceae, Alloprevotella, and Prevotellaceae were the dominant. Flow cytometry results showed that l-theanine decreased helper T (Th)1 and Th17 immune responses, and increased Th2 and T-regulatory immune responses via regulation of antigen-presenting cell responses, such as dendritic cells and macrophages. Therefore, l-theanine regulated the immune response of colon CD4 + T cells to dendritic cell and macrophage antigen presentation via tryptophan-, short chain fatty acid-, and bile acid-related microbiota, thereby preventing dextran sulfate sodium-induced UC.}, }
@article {pmid39921898, year = {2025}, author = {Cohen, S and Spencer, EA and Dolinger, MT and Suskind, DL and Mitrova, K and Hradsky, O and Conrad, MA and Kelsen, JR and Uhlig, HH and Tzivinikos, C and Henderson, P and Wlazlo, M and Hackl, L and Shouval, DS and Bramuzzo, M and Urlep, D and Olbjørn, C and D'Arcangelo, G and Pujol-Muncunill, G and Yogev, D and Kang, B and Gasparetto, M and Rungoe, C and Kolho, KL and Hojsak, I and Norsa, L and Rinawi, F and Sansotta, N and Rimon, RM and Granot, M and Scarallo, L and Trindade, E and Rodríguez-Belvís, MV and Turner, D and Yerushalmy-Feler, A}, title = {Upadacitinib for Induction of Remission in Paediatric Crohn's Disease: An International Multicentre Retrospective Study.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {61}, number = {8}, pages = {1372-1380}, pmid = {39921898}, issn = {1365-2036}, mesh = {Humans ; Retrospective Studies ; *Crohn Disease/drug therapy ; Male ; Female ; Adolescent ; Remission Induction ; *Heterocyclic Compounds, 3-Ring/therapeutic use/adverse effects ; Treatment Outcome ; Child ; }, abstract = {BACKGROUND: There are scarce data available on upadacitinib in children with Crohn's disease (CD).<br><br>AIM: To evaluate the effectiveness and safety of upadacitinib as an induction therapy in paediatric CD.<br><br>METHODS: This was a multicentre retrospective study between 2022 and 2024 of children treated with upadacitinib for induction of remission of active CD conducted in 30 centres worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN. We recorded demographic, clinical and laboratory data and adverse events (AEs) at week 8 post-induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle.<br><br>RESULTS: We included 100 children (median age 15.8 [interquartile range 14.3-17.2]). All were previously treated with biologic therapies including 89 with &#x2265;&#x2009;2 biologics. At the end of the 8-week induction period, we observed clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) in 75%, 56% and 52%, respectively. By the end of induction, 68% had achieved normalisation of C-reactive protein, and 58% had faecal calprotectin (FC) <&#x2009;150 mcg/g. There was combined CFR and FC remission in 13/31 children with available data at 8&#x2009;weeks (13% of the ITT population). AEs were recorded in 24 children; the most frequent was acne in 12. Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy.<br><br>CONCLUSION: Upadacitinib is an effective induction therapy for refractory paediatric CD. Efficacy should be weighed against the potential risks of AEs.}, }
@article {pmid39920804, year = {2025}, author = {Mooyottu, S and Muyyarikkandy, MS and Yousefi, F and Li, G and Sahin, O and Burrough, E and Scaria, J and Sponseller, B and Ramirez, A}, title = {Fecal microbiota transplantation modulates jejunal host-microbiota interface in weanling piglets.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {45}, pmid = {39920804}, issn = {2049-2618}, support = {2022-67015-40720//National Institute of Food and Agriculture/ ; 19-216 IPPA//Iowa Pork Producers Association/ ; }, mesh = {Animals ; Swine ; *Fecal Microbiota Transplantation ; *Jejunum/microbiology ; *Gastrointestinal Microbiome ; Weaning ; Feces/microbiology ; Diarrhea/microbiology/therapy/veterinary ; Bacteria/classification/genetics/isolation &amp; purification ; Swine Diseases/microbiology/therapy ; Enterotoxigenic Escherichia coli ; *Host Microbial Interactions ; }, abstract = {BACKGROUND: Weaning-associated enteric diseases are a major concern in the swine industry. This study investigates the effects of fecal microbiota transplantation (FMT) on the jejunum of weanling piglets, a segment of bowel less studied in terms of microbiomic changes despite its primary involvement in major post-weaning enteric diseases, including postweaning diarrhea (PWD). Thirty-two 3-week-old piglets were divided equally into two groups: Control and FMT. The FMT group received fecal microbiota preparation from 3-month-old healthy pigs on the 1st and 3rd day after weaning. Half of each group was inoculated with an enterotoxigenic E. coli (ETEC) isolate 10 days post-FMT. Piglets were euthanized in the third week (14th and 18th days post-FMT) after weaning to collect intestinal tissues and contents for microbiomic, metabolomic, and transcriptomic analyses.<br><br>RESULTS: The jejunal microbiota showed a significant increase in alpha diversity in the third week post-FMT compared with the ileum and colon. FMT significantly enriched the jejunal microbiota composition, while multiple bacterial genera were specifically lacking in control weanling piglets. FMT was strongly associated with the enrichment of the genus Pseudoscardovia of the Bifidobacteriaceae family, which was found lacking in the jejunum of weanling control piglets and inversely associated with the abundance of the genus Bifidobacterium within the same family. Other genera associated with FMT included Solobacterium, Shuttleworthia, and Pseudoraminibacter, whereas bacteria such as Erysipelotrichaceae and Acidaminococcus were identified as most abundant in the control piglets. Metabolomic analysis revealed a significant modulatory effect of FMT on carbohydrate, amino acid, nucleotide, vitamin, and xenobiotic metabolisms, suggesting improved nutrient utilization. Transcriptomic analyses further confirmed the regulatory effects of FMT on gene expression associated with immune, metabolic, barrier, and neuroendocrine functions. Prior FMT treatment in the context of ETEC infection indicated a potential protective role, as evidenced by a significant shift in microbial diversity and metabolomic compositions and decreased diarrhea severity even though no effect on pathogen shedding was evident.<br><br>CONCLUSIONS: This study underscores the promise of FMT in enhancing jejunal health. In addition, the results suggest that FMT could be considered a potential strategy to address conditions associated with small intestinal dysbiosis in swine and other monogastric species with similar gut anatomy and physiology, such as humans. Video Abstract.}, }
@article {pmid39917846, year = {2025}, author = {Jeong, S and Davis, CK and Chokkalla, AK and Kim, B and Park, S and Vemuganti, R}, title = {Fecal microbiota transplantation fails to impart the benefits of circadian-dependent intermittent fasting following ischemic stroke.}, journal = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism}, volume = {45}, number = {4}, pages = {779-789}, pmid = {39917846}, issn = {1559-7016}, support = {R35 NS132184/NS/NINDS NIH HHS/United States ; IK6 BX005690/BX/BLRD VA/United States ; I01 BX006062/BX/BLRD VA/United States ; R01 NS130763/NS/NINDS NIH HHS/United States ; I01 BX005127/BX/BLRD VA/United States ; }, mesh = {*Fasting/physiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Male ; *Ischemic Stroke/therapy/microbiology ; *Circadian Rhythm/physiology ; Animals ; Humans ; Female ; Intermittent Fasting ; }, abstract = {Intermittent fasting (IF) is known to induce significant ischemic tolerance. Diet is a major proponent of gut microbiota, and gut microbial dysbiosis plays a role in post-stroke brain damage. Hence, we currently evaluated whether IF-mediated ischemic tolerance is mediated by gut microbiota. Additionally, circadian cycle is known to modulate post-ischemic outcomes, and thus we further evaluated if gut microbiota would be influenced by prophylactic IF during the inactive phase (fasting during daytime; IIF) or active phase (fasting during nighttime; AIF). The AIF, but not IIF, cohort showed a significantly decreased fecal Firmicutes/Bacteroidetes ratio compared with the ad libitum (AL) cohort. Moreover, the levels of gut microbiota-derived metabolites butyrate and propionate decreased in AL cohort following focal ischemia, whereas they increased in AIF cohort. However, fecal microbiota transplantation (FMT) from IIF or AIF cohort had no significant effects on post-ischemic motor and cognitive function recovery, anxiety-, and depression-like behaviors compared with FMT from AL cohort. Furthermore, FMT from IIF or AIF cohort did not influence the post-ischemic infarct volume, atrophy volume or white matter damage. Overall, the current findings indicate that the beneficial effects of IF after focal ischemia are not mediated by the gut microbiota.}, }
@article {pmid39916498, year = {2025}, author = {Chen, Q and Gao, Y and Li, F and Yuan, L}, title = {The role of gut-islet axis in pancreatic islet function and glucose homeostasis.}, journal = {Diabetes, obesity &amp; metabolism}, volume = {27}, number = {4}, pages = {1676-1692}, pmid = {39916498}, issn = {1463-1326}, support = {82170812//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Homeostasis/physiology ; *Gastrointestinal Microbiome/physiology ; *Islets of Langerhans/metabolism/physiology ; Animals ; *Gastrointestinal Tract/metabolism/microbiology ; *Glucose/metabolism ; Signal Transduction ; }, abstract = {The gastrointestinal tract plays a vital role in the occurrence and treatment of metabolic diseases. Recent studies have convincingly demonstrated a bidirectional axis of communication between the gut and islets, enabling the gut to influence glucose metabolism and energy homeostasis in animals strongly. The 'gut-islet axis' is an essential endocrine signal axis that regulates islet function through the dialogue between intestinal microecology and endocrine metabolism. The discovery of glucagon-like peptide-1 (GLP-1), gastric inhibitory peptide (GIP) and other gut hormones has initially set up a bridge between gut and islet cells. However, the influence of other factors remains largely unknown, such as the homeostasis of the gut microbiota and the integrity of the gut barrier. Although gut microbiota primarily resides and affect intestinal function, they also affect extra-intestinal organs by absorbing and transferring metabolites derived from microorganisms. As a result of this transfer, islets may be continuously exposed to gut-derived metabolites and components. Changes in the composition of gut microbiota can damage the intestinal barrier function to varying degrees, resulting in increased intestinal permeability to bacteria and their derivatives. All these changes contribute to the severe disturbance of critical metabolic pathways in peripheral tissues and organs. In this review, we have outlined the different gut-islet axis signalling mechanisms associated with metabolism and summarized the latest progress in the complex signalling molecules of the gut and gut microbiota. In addition, we will discuss the impact of the gut renin-angiotensin system (RAS) on the various components of the gut-islet axis that regulate energy and glucose homeostasis. This work also indicates that therapeutic approaches aiming to restore gut microbial homeostasis, such as probiotics and faecal microbiota transplantation (FMT), have shown great potential in improving treatment outcomes, enhancing patient prognosis and slowing down disease progression. Future research should further uncover the molecular links between the gut-islet axis and the gut microbiota and explore individualized microbial treatment strategies, which will provide an innovative perspective and approach for the diagnosis and treatment of metabolic diseases.}, }
@article {pmid39915986, year = {2025}, author = {Escobar, C and Aldeguer, X and Vivas, D and Manzano Fernández, S and Gonzalez Caballero, E and Garcia Martín, A and Barrios, V and Freixa-Pamias, R}, title = {The gut microbiota and its role in the development of cardiovascular disease.}, journal = {Expert review of cardiovascular therapy}, volume = {23}, number = {1-2}, pages = {23-34}, doi = {10.1080/14779072.2025.2463366}, pmid = {39915986}, issn = {1744-8344}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Cardiovascular Diseases/microbiology/physiopathology/etiology/therapy ; *Dysbiosis/complications/therapy/microbiology/physiopathology ; Probiotics/administration &amp; dosage ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation/methods ; Animals ; }, abstract = {INTRODUCTION: The pathophysiology of cardiovascular diseases encompasses a complex interplay of genetic and environmental risk factors. Even if traditional risk factors are treated to target, there remains a residual risk.<br><br>AREAS COVERED: This manuscript reviews the potential role of gut microbiota in the development of cardiovascular disease, and as potential target. A systematic search was conducted until 30 October 2024 on PubMed (MEDLINE), using the MeSH terms [Gut microbiota]&#x2009;+&#x2009;[Dysbiosis]&#x2009;+&#x2009;[Cardiovascular]&#x2009;+&#x2009;[TMAO]&#x2009;+&#x2009;[bile acids]&#x2009;+&#x2009;[short-chain fatty acids].<br><br>EXPERT OPINION: The term dysbiosis implies changes in equilibrium, with modifications in the composition and functionality of microbiota and a series of additional factors: reduced diversity and uniformity of microorganisms; reduced short-chain fatty acid-producing bacteria; increased gut permeability; release of metabolites, such as trimethylamine N-oxide, betaine, phenylalanine, tryptophan-kynurenine, phenylacetylglutamine, and lipopolysaccharides; and reduced secondary bile acid excretion, leading to inflammation, oxidative stress, and endothelial dysfunction and facilitating the onset of pathological conditions, including obesity, hypertension, diabetes, atherosclerosis, and heart failure. Attempts to restore gut microbiota balance through different interventions, mainly changes in diet, have been shown to positively affect individual components and metabolites and reduce the risk of cardiovascular disease. In addition, probiotics and prebiotics are potentially useful. Fecal microbiota transplantation is a promising therapy.}, }
@article {pmid39915243, year = {2025}, author = {Zhao, S and Lin, H and Li, W and Xu, X and Wu, Q and Wang, Z and Shi, J and Chen, Y and Ye, L and Xi, L and Chen, L and Yuan, M and Su, J and Gao, A and Jin, J and Ying, X and Wang, X and Ye, Y and Sun, Y and Zhang, Y and Deng, X and Shen, B and Gu, W and Ning, G and Wang, W and Hong, J and Wang, J and Liu, R}, title = {Post sleeve gastrectomy-enriched gut commensal Clostridia promotes secondary bile acid increase and weight loss.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2462261}, pmid = {39915243}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Bile Acids and Salts/metabolism ; *Weight Loss ; Humans ; Mice ; *Clostridium/genetics/metabolism/isolation &amp; purification/classification ; *Gastrectomy ; Male ; *Obesity/surgery/microbiology/metabolism ; Receptors, G-Protein-Coupled/metabolism/genetics ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Feces/microbiology ; Female ; Adult ; Bariatric Surgery ; }, abstract = {The gut microbiome is altered after bariatric surgery and is associated with weight loss. However, the commensal bacteria involved and the underlying mechanism remain to be determined. We performed shotgun metagenomic sequencing in obese subjects before and longitudinally after sleeve gastrectomy (SG), and found a significant enrichment in microbial species in Clostridia and bile acid metabolizing genes after SG treatment. Bile acid profiling further revealed decreased primary bile acids (PBAs) and increased conjugated secondary bile acids (C-SBAs) after SG. Specifically, glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) were increased at different follow-ups after SG, and were associated with the increased abundance of Clostridia and body weight reduction. Fecal microbiome transplantation with post-SG feces increased SBA levels, and alleviated body weight gain in the recipient mice. Furthermore, both Clostridia-enriched spore-forming bacteria and GDCA supplementation increased the expression of genes responsible for lipolysis and fatty acid oxidation in adipose tissue and reduced adiposity via Takeda G-protein-coupled receptor 5 (TGR5) signaling. Our findings reveal post-SG gut microbiome and C-SBAs as contributory to SG-induced weight loss, in part via TGR5 signaling, and suggest SBA-producing gut microbes as a potential therapeutic target for obesity intervention.}, }
@article {pmid39912727, year = {2025}, author = {Ma, X and Li, M and Zhang, Y and Xu, T and Zhou, X and Qian, M and Yang, Z and Han, X}, title = {Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {39912727}, issn = {2050-084X}, support = {32172765//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Wnt Signaling Pathway ; Mice ; *Gastrointestinal Microbiome ; Swine ; *Fecal Microbiota Transplantation ; Bacteroides fragilis/physiology ; *Intestinal Mucosa/microbiology ; Enterotoxigenic Escherichia coli ; *Akkermansia ; *Escherichia coli Infections/therapy/microbiology ; Disease Models, Animal ; Anti-Bacterial Agents ; Mice, Inbred C57BL ; }, abstract = {As the largest mucosal surface, the gut has built a physical, chemical, microbial, and immune barrier to protect the body against pathogen invasion. The disturbance of gut microbiota aggravates pathogenic bacteria invasion and gut barrier injury. Fecal microbiota transplantation (FMT) is a promising treatment for microbiome-related disorders, where beneficial strain engraftment is a significant factor influencing FMT outcomes. The aim of this research was to explore the effect of FMT on antibiotic-induced microbiome-disordered (AIMD) models infected with enterotoxigenic Escherichia coli (ETEC). We used piglet, mouse, and intestinal organoid models to explore the protective effects and mechanisms of FMT on ETEC infection. The results showed that FMT regulated gut microbiota and enhanced the protection of AIMD piglets against ETEC K88 challenge, as demonstrated by reduced intestinal pathogen colonization and alleviated gut barrier injury. Akkermansia muciniphila (A. muciniphila) and Bacteroides fragilis (B. fragilis) were identified as two strains that may play key roles in FMT. We further investigated the alleviatory effects of these two strains on ETEC infection in the AIMD mice model, which revealed that A. muciniphila and B. fragilis relieved ETEC-induced intestinal inflammation by maintaining the proportion of Treg/Th17 cells and epithelial damage by moderately activating the Wnt/β-catenin signaling pathway, while the effect of A. muciniphila was better than B. fragilis. We, therefore, identified whether A. muciniphila protected against ETEC infection using basal-out and apical-out intestinal organoid models. A. muciniphila did protect the intestinal stem cells and stimulate the proliferation and differentiation of intestinal epithelium, and the protective effects of A. muciniphila were reversed by Wnt inhibitor. FMT alleviated ETEC-induced gut barrier injury and intestinal inflammation in the AIMD model. A. muciniphila was identified as a key strain in FMT to promote the proliferation and differentiation of intestinal stem cells by mediating the Wnt/β-catenin signaling pathway.}, }
@article {pmid39911724, year = {2025}, author = {Dutta, SK and Firnberg, E and Verma, S and Phillips, L and Nair, PP}, title = {Detection of Human Y Chromosome and the SRY Gene in Fecal Samples of Female Patients Following Fecal Microbiota Transplantation.}, journal = {Gastro hep advances}, volume = {4}, number = {2}, pages = {100568}, pmid = {39911724}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: We have postulated that fecal microbiota transplantation (FMT) is associated with transfer of microbiota from the donor and engraftment of intestinal epithelial cells in the recipient's colonic mucosa enabling the restoration of a stable microbial environment.<br><br>METHODS: We analyzed the presence of human Y chromosome (ChrY) and sex-determining region Y (SRY) gene within total human DNA extracted from fecal samples collected from 30 donors and 22 recurrent Clostridium difficile infection (RCDI) patients before and up to 24 months after FMT. A next-generation sequencing data analysis pipeline was applied to quantify the percentage of reads aligning to human ChrY. SRY gene detection was also performed by quantitative polymerase chain reaction and droplet digital polymerase chain reaction.<br><br>RESULTS: A significantly higher percentage of ChrY reads were identified in fecal samples of male donors as compared to female donor (P < .0001). Fecal samples collected from female RCDI patients who received FMT from male donors showed a significantly (P < .05) higher percentage of ChrY reads compared to female samples without male FMT donors. Four female patients with RCDI who received FMT from male donors showed a very large percent ChrY increase post-FMT even several months after FMT. SRY gene signal was detected by droplet digital polymerase chain reaction in 7 of the 11 fecal samples collected from the male donor pool but none from the female pool.<br><br>CONCLUSION: These observations clearly demonstrate the presence of ChrY and SRY gene signal in stool samples collected from male patients. The presence of increased ChrY in the stool samples of female RCDI patients after FMT from a male donor suggests possible engraftment of exfoliated intestinal epithelial cells in a subset of these patients.}, }
@article {pmid39910418, year = {2025}, author = {Li, L and Mo, Q and Wan, Y and Zhou, Y and Li, W and Li, W}, title = {Antimicrobial peptide AP2 ameliorates Salmonella Typhimurium infection by modulating gut microbiota.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {64}, pmid = {39910418}, issn = {1471-2180}, support = {No. 82003436//Young Scientists Fund of the National Natural Science Foundation of China/ ; No. 2011BAD26B02//the 'twelfth five-year-plan' in National Support Program for Science and Technology for rural development in China/ ; No. 31472128//Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Salmonella typhimurium/drug effects ; Mice ; Cecum/microbiology/pathology ; *Antimicrobial Peptides/pharmacology/administration &amp; dosage ; RNA, Ribosomal, 16S/genetics ; *Salmonella Infections/microbiology/drug therapy ; Feces/microbiology ; Cytokines/blood ; Disease Models, Animal ; *Antimicrobial Cationic Peptides/administration &amp; dosage/pharmacology ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Male ; Bacteria/classification/genetics/drug effects ; *Salmonella Infections, Animal/microbiology/drug therapy ; }, abstract = {BACKGROUND: Endogenous antimicrobial peptides and proteins are essential for shaping and maintaining a healthy gut microbiota, contributing to anti-inflammatory responses and resistance to pathogen colonization. Salmonella enterica subsp. enterica serovar Typhimurium (ST) infection is one of the most frequently reported bacterial diseases worldwide. Manipulation of the gut microbiota through exogenous antimicrobial peptides may protect against ST colonization and improve clinical outcomes.<br><br>RESULTS: This study demonstrated that oral administration of the antimicrobial peptide AP2 (2&#xa0;&#xb5;g /mouse), an optimized version of native apidaecin IB (AP IB), provided protective effects against ST infection in mice. These effects were evidenced by reduced ST-induced body weight loss and lower levels of serum inflammatory cytokines. A 16&#xa0;S rRNA-based analysis of the cecal microbiota revealed that AP2 significantly modulated the gut microbiota, increasing the relative abundance of Bifidobacterium while decreasing that of Akkermansia at the genus level. Furthermore, the transplantation of fecal microbiota from AP2-treated donor mice, rather than from Control mice, significantly reduced cecal damage caused by ST and decreased the concentration of ST by one order of magnitude after infection.<br><br>CONCLUSIONS: These findings reveal a novel mechanism by which exogenous antimicrobial peptides mitigate Salmonella Typhimurium infection through the modulation of gut microbiota.}, }
@article {pmid39909032, year = {2025}, author = {Zhu, X and Hu, M and Huang, X and Li, L and Lin, X and Shao, X and Li, J and Du, X and Zhang, X and Sun, R and Tong, T and Ma, Y and Ning, L and Jiang, Y and Zhang, Y and Shao, Y and Wang, Z and Zhou, Y and Ding, J and Zhao, Y and Xuan, B and Zhang, H and Zhang, Y and Hong, J and Fang, JY and Xiao, X and Shen, B and He, S and Chen, H}, title = {Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses.}, journal = {Cell metabolism}, volume = {37}, number = {4}, pages = {806-823.e6}, doi = {10.1016/j.cmet.2024.12.013}, pmid = {39909032}, issn = {1932-7420}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Immunotherapy/methods ; *Neoplasms/therapy/metabolism/microbiology/immunology ; Metabolome ; Female ; Male ; Immune Checkpoint Inhibitors/therapeutic use ; Middle Aged ; Aged ; }, abstract = {Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but remains effective in only a subset of patients. Emerging evidence suggests that the gut microbiome and its metabolites critically influence ICB efficacy. In this study, we performed a multi-omics analysis of fecal microbiomes and metabolomes from 165 patients undergoing anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy, identifying microbial and metabolic entities associated with treatment response. Integration of data from four public metagenomic datasets (n = 568) uncovered cross-cohort microbial and metabolic signatures, validated in an independent cohort (n = 138). An integrated predictive model incorporating these features demonstrated robust performance. Notably, we characterized five response-associated enterotypes, each linked to specific bacterial taxa and metabolites. Among these, the metabolite phenylacetylglutamine (PAGln) was negatively correlated with response and shown to attenuate anti-PD-1 efficacy in vivo. This study sheds light on the interplay among the gut microbiome, the gut metabolome, and immunotherapy response, identifying potential biomarkers to improve treatment outcomes.}, }
@article {pmid39908366, year = {2025}, author = {Wu, F and Lin, S and Luo, H and Wang, C and Liu, J and Zhu, X and Pang, Y}, title = {Noncontact microbiota transplantation by core-shell microgel-enabled nonleakage envelopment.}, journal = {Science advances}, volume = {11}, number = {6}, pages = {eadr7373}, pmid = {39908366}, issn = {2375-2548}, mesh = {*Gastrointestinal Microbiome ; *Microgels/chemistry ; Humans ; Animals ; *Fecal Microbiota Transplantation/methods ; Probiotics ; Methacrylates/chemistry ; Hydrogen-Ion Concentration ; }, abstract = {Transplantation of beneficial bacteria to specific microbiota has been widely exploited to treat diseases by reshaping a healthy microbial structure. However, direct exposure of exogenous bacteria in vivo suffers from low bioavailability and infection risk. Here, we describe a noncontact microbiota transplantation system (NMTS) by core-shell microgel-enabled nonleakage envelopment. Bacteria are encapsulated into the core of core-shell microgels via two-step light-initiated emulsion polymerization of gelatin methacrylate. NMTS is versatile for biocontainment of diverse strains, showing near complete encapsulation and negligible influence on bacterial activity. As a proof-of-concept study on probiotic transplantation to the gut microbiota, NMTS demonstrates the shielding effect to protect sealed bacteria from intraluminal insults of low pH and bile acid, the toughness to prevent bacterial leakage during entire gastrointestinal passage and reduce infection risk, and the permeability to release beneficial metabolites and reconstruct a balanced intestinal microbial structure, proposing a contactless fashion for advanced microbiota transplantation.}, }
@article {pmid39908176, year = {2025}, author = {}, title = {Correction to: A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {80}, number = {1}, pages = {242-243}, doi = {10.1093/cid/ciaf032}, pmid = {39908176}, issn = {1537-6591}, }
@article {pmid39907559, year = {2025}, author = {Ding, Q and Xue, J and Li, N and Hu, Z and Song, J}, title = {Fecal microbiota transplantation alleviates radiation enteritis by modulating gut microbiota and metabolite profiles.}, journal = {Biomolecules &amp; biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2025.11835}, pmid = {39907559}, issn = {2831-090X}, abstract = {This study investigates the safety and underlying mechanisms of fecal microbiota transplantation (FMT) in treating radiation enteritis (RE). A rat model of RE was established with six groups: NC, RT, H-FMT, modified FMT (M-FMT), L-FMT, and BTAC. The therapeutic effects of FMT were assessed using the Disease Activity Index (DAI), histological analysis, and biochemical tests, including ink-propelling, xylitol exclusion, and enzyme-linked immunosorbent assay (ELISA). Gut microbiota alterations and fecal metabolism were analyzed via 16S rDNA sequencing and targeted metabolomics. The results demonstrated that FMT, particularly in the M-FMT group, effectively alleviated RE by reducing DAI scores, histological damage, and inflammatory markers while enhancing enzyme activity, superoxide dismutase (SOD) levels, and intestinal absorption. FMT also modulated gut microbiota composition, increasing beneficial species, such as Blautia wexlerae and Romboutsia timonensis while decreasing Enterococcus ratti. Metabolomics analysis revealed that FMT influenced niacin, nicotinamide, and starch metabolism, with notable changes in pantothenic acid and fatty acid levels. Spearman correlation analysis further indicated that these microbial shifts were associated with improved metabolic profiles. Overall, FMT mitigates RE by regulating gut microbiota and metabolites, with pantothenic acid and fatty acids emerging as potential therapeutic targets. Further research is needed to explore the underlying mechanisms in greater detail.}, }
@article {pmid39906503, year = {2025}, author = {Song, Q and Zhang, K and Li, S and Weng, S}, title = {Trichosanthes kirilowii Maxim. Polysaccharide attenuates diabetes through the synergistic impact of lipid metabolism and modulating gut microbiota.}, journal = {Current research in food science}, volume = {10}, number = {}, pages = {100977}, pmid = {39906503}, issn = {2665-9271}, abstract = {Polysaccharide, a chain of sugars bound by glycosidic bonds, have a wide range of physiological activities, including hypoglycemic activity. In present study, we established T2DM mice models to explore the effects and mechanism of Trichosanthes kirilowii Maxim polysaccharide (TMSP1) on high-fat diet/streptozotocin (HF-STZ) induced diabetes mice. The results showed that high-fat diet significantly increased the oral glucose tolerance test (OGTT), viscera index, oxidative stress, impaired glucose tolerance, decreased body weight, immune response and short-chain fatty acid (SCFAs) content, and disrupted the balance of intestinal flora structure. However, after 6 weeks of TMSP1 intervention decreased lipid accumulation, ameliorated gut microbiota dysbiosis by increasing SCFAs-producing bacteria and mitigated intestinal inflammation and oxidative stress. Moreover, TMSP1 significantly restored the integrity of the intestinal epithelial barrier and mucus barrier. The results of fecal microbiota transplantation confirmed that TMSP1 exerted hypoglycemic effect through regulating intestinal flora to a certain extent. Collectively, the findings revealed TMSP1 intervention inhibits hyperglycemia by improving gut microbiota disorder, lipid metabolism, and inflammation. Hence, TMSP1 may be an effective measure to ameliorate HF-STZ induced diabetes.}, }
@article {pmid39905483, year = {2025}, author = {Lin, Z and Feng, Y and Wang, J and Men, Z and Ma, X}, title = {Microbiota governs host chenodeoxycholic acid glucuronidation to ameliorate bile acid disorder induced diarrhea.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {36}, pmid = {39905483}, issn = {2049-2618}, mesh = {Animals ; *Chenodeoxycholic Acid/metabolism ; *Diarrhea/microbiology/metabolism/etiology ; Mice ; *Gastrointestinal Microbiome/physiology ; *Bile Acids and Salts/metabolism ; Swine ; Limosilactobacillus reuteri/metabolism ; *Glucuronides/metabolism ; Fecal Microbiota Transplantation ; Intestinal Mucosa/metabolism/microbiology ; Sirtuin 1/metabolism ; Colon/microbiology/metabolism ; Disease Models, Animal ; Humans ; }, abstract = {BACKGROUND: Disorder in bile acid (BA) metabolism is known to be an important factor contributing to diarrhea. However, the pathogenesis of BA disorder-induced diarrhea remains unclear.<br><br>METHODS: The colonic BA pool and microbiota between health piglets and BA disorder-induced diarrheal piglets were compared. Fecal microbiota transplantation and various cell experiments further indicated that chenodeoxycholic acid (CDCA) metabolic disorder produced CDCA-3&#x3b2;-glucuronide, which is the main cause of BA disorder diarrhea. Non-targeted metabolomics uncovered the inhibition of the BA glucuronidation by Lactobacillus reuteri (L. reuteri) is through deriving indole-3-carbinol (I3C). In vitro, important gene involved in the reduction of BA disorder induced-diarrhea were screened by RNA transcriptomics sequencing, and activation pathway of FXR-SIRT1-LKB1 to alleviate BA disorder diarrhea and P53-mediated apoptosis were proposed in vitro by multifarious siRNA interference, CO-IP, immunofluorescence, and so on, which mechanism was also verified in a variety of mouse models.<br><br>RESULTS: Here, we reveal for the first time that core microbiota derived I3C represses gut epithelium glucuronidation, particularly 3&#x3b2;-glucuronic CDCA production, which reaction is mediated by host UDP glucuronosyltransferase family 1 member A4 (UGT1A4) and necessary of BA disorder induced diarrhea. Mechanistically, L. reuteri derived I3C activates aryl hydrocarbon receptor to decrease UGT1A4 transcription and CDCA-3&#x3b2;-glucuronide content, thereby upregulating FXR-SIRT1-LKB1 signal. LKB1 binds with P53 based on protein interaction, ultimately resists to apoptosis and diarrhea. Moreover, I3C assists CDCA to attain the ameliorative effects of FXR activation in BA disorder diarrhea, through reversion of abnormal metabolism pathway, improving the outcomes of CDCA supplement.<br><br>CONCLUSION: These findings uncover the crucial interplay between gut epithelial cells and microbes, highlighting UGT1A4-mediated conversion of CDCA-3&#x3b2;-glucuronide as a key target for ameliorating BA disorder-induced diarrhea. Video Abstract.}, }
@article {pmid39904968, year = {2025}, author = {Ashiqueali, SA and Hayslip, N and Chaudhari, DS and Schneider, A and Zhu, X and Rubis, B and Seavey, CE and Alam, MT and Hussein, R and Noureddine, SA and Golusinska-Kardach, E and Pazdrowski, P and Yadav, H and Masternak, MM}, title = {Fecal microbiota transplant from long-living Ames dwarf mice alters the microbial composition and biomarkers of liver health in normal mice.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {39904968}, issn = {2509-2723}, support = {R56AG074499/NH/NIH HHS/United States ; R56AG069676/NH/NIH HHS/United States ; R56AG064075/NH/NIH HHS/United States ; RF1AG071762/NH/NIH HHS/United States ; R21AG072379/NH/NIH HHS/United States ; U01AG076928/NH/NIH HHS/United States ; W81XWH-18-PRARP AZ180098//U.S. Department of Defense/ ; 22A17//Florida Department of Health/ ; 22A17//Florida Department of Health/ ; HORIZON 2020-MSCA-RISE//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; HORIZON 2020-MSCA-RISE//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; }, abstract = {Aging is associated with intestinal dysbiosis, a condition characterized by diminished microbial biodiversity and inflammation. This leads to increased vulnerability to extraintestinal manifestations such as autoimmune, metabolic, and neurodegenerative conditions thereby accelerating mortality. As such, modulation of the gut microbiome is a promising way to extend healthspan. In this study, we explore the effects of fecal microbiota transplant (FMT) from long-living Ames dwarf donors to their normal littermates, and vice versa, on the recipient gut microbiota and liver transcriptome. Importantly, our previous studies highlight differences between the microbiome of Ames dwarf mice relative to their normal siblings, potentially contributing to their extended lifespan and remarkable healthspan. Our findings demonstrate that FMT from Ames dwarf mice to normal mice significantly alters the recipient's gut microbiota, potentially reprogramming bacterial functions related to healthy aging, and changes the liver transcriptome, indicating improved metabolic health. Particularly, the microbiome of Ames dwarf mice, characterized by a higher abundance of beneficial bacterial families such as Peptococcaceae, Oscillospiraceae, and Lachnospiraceae, appears to play a crucial role in modulating these effects. Alongside, our mRNA sequencing and RT-PCR validation reveals that FMT may contribute to the significant downregulation of p21, Elovl3, and Insig2, genes involved with cellular senescence and liver metabolic pathways. Our data suggest a regulatory axis exists between the gut and liver, highlighting the potential of microbiome-targeted therapies in promoting healthy aging. Future research should focus on functional validation of altered microbial communities and explore the underlying biomolecular pathways that confer geroprotection.}, }
@article {pmid39904603, year = {2025}, author = {Lou, F and Yan, L and Luo, S and Dong, Y and Xu, J and Kang, N and Wang, H and Liu, Y and Pu, J and Yang, B and Cannon, RD and Xie, P and Ji, P and Jin, X}, title = {Dysbiotic oral microbiota-derived kynurenine, induced by chronic restraint stress, promotes head and neck squamous cell carcinoma by enhancing CD8[+] T cell exhaustion.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-333479}, pmid = {39904603}, issn = {1468-3288}, abstract = {BACKGROUND: Chronic restraint stress (CRS) is a tumour-promoting factor. However, the underlying mechanism is unknown.<br><br>OBJECTIVE: We aimed to investigate whether CRS promotes head and neck squamous cell carcinoma (HNSCC) by altering the oral microbiota and related metabolites and whether kynurenine (Kyn) promotes HNSCC by modulating CD8[+] T cells.<br><br>DESIGN: 4-nitroquinoline-1-oxide (4NQO)-treated mice were exposed to CRS. Germ-free mice treated with 4NQO received oral microbiota transplants from either CRS or control mouse donors. 16S rRNA gene sequencing and liquid chromatography-mass spectrometry were performed on mouse saliva, faecal and plasma samples to investigate alterations in their microbiota and metabolites. The effects of Kyn on HNSCC were studied using the 4NQO-induced HNSCC mouse model.<br><br>RESULTS: Mice subjected to CRS demonstrated a higher incidence of HNSCC and oral microbial dysbiosis than CRS-free control mice. Pseudomonas and Veillonella species were enriched while certain oral bacteria, including Corynebacterium and Staphylococcus species, were depleted with CRS exposure. Furthermore, CRS-altered oral microbiota promoted HNSCC formation, caused oral and gut barrier dysfunction, and induced a host metabolome shift with increased plasma Kyn in germ-free mice exposed to 4NQO treatment. Under stress conditions, we also found that Kyn activated aryl hydrocarbon receptor (AhR) nuclear translocation and deubiquitination in tumour-reactive CD8[+] T cells, thereby promoting HNSCC tumourigenesis.<br><br>CONCLUSION: CRS-induced oral microbiota dysbiosis plays a protumourigenic role in HNSCC and can influence host metabolism. Mechanistically, under stress conditions, Kyn promotes CD8[+] T cell exhaustion and HNSCC tumourigenesis through stabilising AhR by its deubiquitination.}, }
@article {pmid39903739, year = {2025}, author = {Men, J and Li, H and Cui, C and Ma, X and Liu, P and Yu, Z and Gong, X and Yao, Y and Ren, J and Zhao, C and Song, B and Yin, K and Wu, J and Liu, W}, title = {Fecal bacteria transplantation replicates aerobic exercise to reshape the gut microbiota in mice to inhibit high-fat diet-induced atherosclerosis.}, journal = {PloS one}, volume = {20}, number = {2}, pages = {e0314698}, pmid = {39903739}, issn = {1932-6203}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Atherosclerosis/therapy/etiology/microbiology/pathology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Male ; Mice ; *Physical Conditioning, Animal ; Mice, Inbred C57BL ; Disease Models, Animal ; Lipids/blood ; }, abstract = {Aerobic exercise exerts a significant impact on the gut microbiota imbalance and atherosclerosis induced by a high-fat diet. However, whether fecal microbiota transplantation, based on aerobic exercise, can improve atherosclerosis progression remains unexplored. In this study, we utilized male C57 mice to establish models of aerobic exercise and atherosclerosis, followed by fecal microbiota transplantation(Fig 1a). Firstly, we analyzed the body weight, somatotype, adipocyte area, and aortic HE images of the model mice. Our findings revealed that high-fat diet -induced atherosclerosis mice exhibited elevated lipid accumulation, larger adipocyte area, and more severe atherosclerosis progression. Additionally, we assessed plasma lipid levels, inflammatory factors, and gut microbiota composition in each group of mice. high-fat diet -induced atherosclerosis mice displayed dyslipidemia along with inflammatory responses and reduced gut microbiota diversity as well as abundance of beneficial bacteria. Subsequently performing fecal microbiota transplantation demonstrated that high-fat diet -induced atherosclerosis mice experienced weight loss accompanied by reduced lipid accumulation while normalizing their gut microbiota profile; furthermore it significantly improved blood lipids and inflammation markers thereby exhibiting notable anti- atherosclerosis effects. The findings suggest that aerobic exercise can modify gut microbiota composition and improve high-fat diet-induced atherosclerosis(Fig 1b). Moreover, these beneficial effects can be effectively transmitted through fecal microbiota transplantation, offering a promising therapeutic approach for managing atherosclerosis.}, }
@article {pmid39902926, year = {2025}, author = {Rahman, R and Fouhse, JM and Ju, T and Fan, Y and Bhardwaj, T and Brook, RK and Nosach, R and Harding, J and Willing, BP}, title = {The impact of wild-boar-derived microbiota transplantation on piglet microbiota, metabolite profile, and gut proinflammatory cytokine production differs from sow-derived microbiota.}, journal = {Applied and environmental microbiology}, volume = {91}, number = {3}, pages = {e0226524}, pmid = {39902926}, issn = {1098-5336}, support = {res0030386//Alberta Livestock and Meat Agency (ALMA)/ ; RGPIN-2019-06336//Canadian Government | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Cytokines/metabolism/immunology ; Swine/microbiology ; *Sus scrofa/microbiology ; *Fecal Microbiota Transplantation/veterinary ; *Metabolome ; }, abstract = {Colonization of co-evolved, species-specific microbes in early life plays a crucial role in gastrointestinal development and immune function. This study hypothesized that modern pig production practices have resulted in the loss of co-evolved species and critical symbiotic host-microbe interactions. To test this, we reintroduced microbes from wild boars (WB) into conventional piglets to explore their colonization dynamics and effects on gut microbial communities, metabolite profiles, and immune responses. At postnatal day (PND) 21, 48 piglets were assigned to four treatment groups: (i) WB-derived mixed microbial community (MMC), (ii) sow-derived MMC, (iii) a combination of WB and sow MMC (Mix), or (iv) Control (PBS). Post-transplantation analyses at PND 48 revealed distinct microbial communities in WB-inoculated piglets compared with Controls, with trends toward differentiation from Sow but not Mix groups. WB-derived microbes were more successful in colonizing piglets, particularly in the Mix group, where they competed with Sow-derived microbes. WB group cecal digesta enriched with Lactobacillus helveticus, Lactobacillus mucosae, and Lactobacillus pontis. Cecal metabolite analysis showed that WB piglets were enriched in histamine, acetyl-ornithine, ornithine, citrulline, and other metabolites, with higher histamine levels linked to Lactobacillus abundance. WB piglets exhibited lower cecal IL-1β and IL-6 levels compared with Control and Sow groups, whereas the Mix group showed reduced IFN-γ, IL-2, and IL-6 compared with the Sow group. No differences in weight gain, fecal scores, or plasma cytokines were observed, indicating no adverse effects. These findings support that missing WB microbes effectively colonize domestic piglets and may positively impact metabolite production and immune responses.IMPORTANCEThis study addresses the growing concern over losing co-evolved, species-specific microbes in modern agricultural practices, particularly in pig production. The implementation of strict biosecurity measures and widespread antibiotic use in conventional farming systems may disrupt crucial host-microbe interactions that are essential for gastrointestinal development and immune function. Our research demonstrates that by reintroducing wild boar-derived microbes into domestic piglets, these microbes can successfully colonize the gut, influence microbial community composition, and alter metabolite profiles and immune responses without causing adverse effects. These findings also suggest that these native microbes can fill an intestinal niche, positively impacting immune activation. This research lays the groundwork for future strategies to enhance livestock health and performance by restoring natural microbial populations that produce immune-modulating metabolites.}, }
@article {pmid39901991, year = {2025}, author = {Hemachandra, S and Rathnayake, SN and Jayamaha, AA and Francis, BS and Welmillage, D and Kaur, DN and Zaw, HK and Zaw, LT and Chandra, HA and Abeysekera, ME}, title = {Fecal Microbiota Transplantation as an Alternative Method in the Treatment of Obesity.}, journal = {Cureus}, volume = {17}, number = {1}, pages = {e76858}, pmid = {39901991}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for various health conditions, particularly obesity and metabolic disorders. This review examines the mechanisms underlying FMT, including its role in restoring gut microbiota diversity and enhancing immunomodulatory functions, which are essential for maintaining overall health. Recent studies indicate that FMT can significantly improve body weight and metabolic parameters, suggesting its potential as an alternative or complementary treatment to current obesity therapies. However, the effectiveness of FMT depends on several factors, including the composition of the donor microbiota, recipient characteristics, and concomitant medications or dietary interventions. Despite its great promise, challenges such as standardized protocols, donor screening, and the need for a deeper understanding of gut microbiota dynamics remain key hurdles. Future research should focus on elucidating the specific microbial compositions necessary for optimal therapeutic outcomes and exploring personalized FMT approaches tailored to individual patient profiles. This evolving field presents exciting opportunities for innovative strategies in obesity treatment, warranting further investigation and clinical application.}, }
@article {pmid39901521, year = {2025}, author = {Kappel, SS and Sangild, PT and Zachariassen, G and Andersen, JH and Rasmussen, KK and Jeppesen, PB and Aunsholt, L}, title = {Protein and energy digestibility in preterm infants fed fortified human milk.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.70000}, pmid = {39901521}, issn = {1536-4801}, support = {//Innovation Fund Denmark (NEOCOL grant 6150-00004B)./ ; }, abstract = {OBJECTIVES: The objective of the present study is to determine whether the apparent nutrient digestibility differs between very preterm infants fortified with bovine colostrum (BC) compared to those fortified with a conventional fortifier (CF), building on previous findings that BC was associated with looser stools and reduced need for laxatives in very preterm infants (VPI).<br><br>METHODS: We conducted a 24-h digestibility balance study in 10 VPIs to assess the retention of protein, energy, and wet-weight following the intake of fortified human milk and collection of faecal excretions. Infants (n&#x2009;=&#x2009;5) were matched by gestational age and birthweight.<br><br>RESULTS: In the 10 infants, the mean gestational age and birthweight were 28&#x2009;&#xb1;&#x2009;1 weeks and 899&#x2009;&#xb1;&#x2009;182&#x2009;g, respectively. Infants fortified with BC had a higher faecal energy loss compared with infants fortified with CF (BC: 178 [range 111-205] vs. CF: 153 [96-235] kJ/kg, p&#x2009;<&#x2009;0.05). No differences (p&#x2009;>&#x2009;0.05) were found for wet-weight intake (421 [360-427] vs. 494 [328-500] kJ/kg), relative absorption of protein (60 [33-75] vs. 50 [33-75]%) or absolute protein absorption (249 [159-310) vs. 281 [210-347]).<br><br>CONCLUSION: Nutrient absorption was similar between groups although higher energy loss indicates reduced overall digestibility of BC versus CF, however, with a large variation within each group. Studies on more infants are required to confirm these results. A 24-h digestibility balance study can successfully be used to assess nutrient and energy retention in preterm infants.}, }
@article {pmid39900090, year = {2025}, author = {Tay, SW and Low, AHL}, title = {Is faecal microbiota transplantation ready for prime time in systemic sclerosis?.}, journal = {The Lancet. Rheumatology}, volume = {7}, number = {5}, pages = {e305-e307}, doi = {10.1016/S2665-9913(24)00376-X}, pmid = {39900090}, issn = {2665-9913}, }
@article {pmid39900089, year = {2025}, author = {Fretheim, H and Barua, I and Bakland, G and Dhainaut, A and Halse, AK and Carstens, MN and Didriksen, H and Midtvedt, &#xd8; and Lundin, KEA and Aabakken, L and Sarna, VK and Zaré, HK and Khanna, D and Distler, O and Midtvedt, T and Bækkevold, ES and Olsen, IC and Domanska, D and Pesonen, ME and Molberg, &#xd8; and Hoffmann-Vold, AM}, title = {Faecal microbiota transplantation in patients with systemic sclerosis and lower gastrointestinal tract symptoms in Norway (ReSScue): a phase 2, randomised, double-blind, placebo-controlled trial.}, journal = {The Lancet. Rheumatology}, volume = {7}, number = {5}, pages = {e323-e332}, doi = {10.1016/S2665-9913(24)00334-5}, pmid = {39900089}, issn = {2665-9913}, mesh = {Humans ; Female ; Middle Aged ; Male ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; *Scleroderma, Systemic/complications/therapy ; Adult ; Aged ; Norway ; Aged, 80 and over ; Treatment Outcome ; Adolescent ; Young Adult ; *Diarrhea/therapy/etiology ; *Gastrointestinal Diseases/therapy/etiology ; Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Gastrointestinal tract involvement is highly prevalent in systemic sclerosis, with few treatment options. We assessed the efficacy and safety of faecal microbiota transplantation using standardised anaerobic cultivated human intestinal microbiome (ACHIM) as a novel treatment option for patients with systemic sclerosis and symptomatic lower gastrointestinal tract involvement.<br><br>METHODS: In this phase 2, randomised, double-blind, placebo-controlled trial done at four university hospitals in Norway, we enrolled adults aged 18-85 years with systemic sclerosis and moderate-to-severe lower gastrointestinal tract symptoms (bloating or diarrhoea). Participants were randomly assigned 1:1 to intestinal infusions of placebo or ACHIM at weeks 0 and 2, stratified by worst symptom (bloating or diarrhoea). The primary endpoint was change in worst lower gastrointestinal tract symptom (bloating or diarrhoea) from week 0 to week 12, measured using the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 scoring system in the intention-to-treat population. Safety was assessed at weeks 0, 2, 4, 6, and 12 in all participants who received at least one infusion. A person with lived experience of systemic sclerosis was involved in the study planning and conduct. This trial was registered at ClinicalTrials.gov, NCT04300426.<br><br>FINDINGS: Between Sept 24, 2020, and Jan 14, 2022, 67 participants were enrolled and randomly allocated to placebo (n=34) or ACHIM (n=33). Mean age was 58&#xb7;91 years (SD 11&#xb7;59). 62 (93%) of 67 participants were women, five (7%) were men, and 50 (75%) were anti-centromere antibody positive. Change in worst lower gastrointestinal tract symptom from week 0 to week 12 did not differ between participants who received ACHIM (-0&#xb7;13, 95% CI -0&#xb7;37 to 0&#xb7;11) and participants who received placebo (-0&#xb7;33, -0&#xb7;57 to -0&#xb7;09; average marginal effect 0&#xb7;20, 95% CI -0&#xb7;12 to 0&#xb7;52; p=0&#xb7;22). Adverse events, mostly mild and short-lived gastrointestinal tract symptoms, were reported by 16 (48%) of 33 participants in the ACHIM group and 19 (56%) of 34 in the placebo group. During gastroscopy, one participant had a duodenal perforation.<br><br>INTERPRETATION: Faecal microbiota transplantation with ACHIM was well tolerated in participants with systemic sclerosis but did not result in an improvement in lower gastrointestinal tract symptoms.<br><br>FUNDING: KLINBEFORSK.<br><br>TRANSLATION: For the Norwegian translation of the abstract see Supplementary Materials section.}, }
@article {pmid39899452, year = {2025}, author = {Chaki, T and Horiguchi, Y and Tachibana, S and Sato, S and Hirahata, T and Nishihara, N and Kii, N and Yoshikawa, Y and Hayamizu, K and Yamakage, M}, title = {Gut Microbiota Influences Developmental Anesthetic Neurotoxicity in Neonatal Rats.}, journal = {Anesthesia and analgesia}, volume = {}, number = {}, pages = {}, doi = {10.1213/ANE.0000000000007410}, pmid = {39899452}, issn = {1526-7598}, abstract = {BACKGROUND: Anesthetic exposure during childhood is significantly associated with impairment of neurodevelopmental outcomes; however, the causal relationship and detailed mechanism of developmental anesthetic neurotoxicity remain unclear. Gut microbiota produces various metabolites and influences the brain function and development of the host. This relationship is referred to as the gut-brain axis. Gut microbiota may influence developmental anesthetic neurotoxicity caused by sevoflurane exposure. This study investigated the effect of changes in the composition of gut microbiota after fecal microbiota transplantation on spatial learning disability caused by developmental anesthetic neurotoxicity in neonatal rats.<br><br>METHODS: Neonatal rats were allocated into the Control (n = 10) and Sevo (n = 10) groups in Experiment 1 and the Sevo (n = 20) and Sevo+FMT (n = 20) groups in Experiment 2, according to the randomly allocated mothers' group. The rats in Sevo and Sevo+FMT groups were exposed to 2.1% sevoflurane for 2 hours on postnatal days 7 to 13. Neonatal rats in the Sevo+FMT group received fecal microbiota transplantation immediately after sevoflurane exposure on postnatal days 7 to 13. The samples for fecal microbiota transplantation were obtained from nonanesthetized healthy adult rats. Behavioral tests, including Open field, Y-maze, Morris water maze, and reversal Morris water maze tests, were performed to evaluate spatial learning ability on postnatal days 26 to 39.<br><br>RESULTS: Experiment 1 revealed that sevoflurane exposure significantly altered the gut microbiota composition. The relative abundance of Roseburia (effect value: 1.01) and Bacteroides genus (effect value: 1.03) increased significantly after sevoflurane exposure, whereas that of Lactobacillus (effect value: -1.20) decreased significantly. Experiment 2 revealed that fecal microbiota transplantation improved latency to target (mean &#xb1; SEM; Sevo group: 9.7 &#xb1; 8.2 seconds vs, Sevo+FMT group: 2.7 &#xb1; 2.4 seconds, d=1.16, 95% confidence interval: -12.7 to -1.3 seconds, P = .019) and target zone crossing times (Sevo group: 2.4 &#xb1; 1.6 vs, Sevo+FMT group: 5.4 &#xb1; 1.4, d=1.99, 95% confidence interval: 2.0-5.0, P < .001) in the reversal Morris water maze test. Microbiota analysis revealed that the &#x3b1;-diversity of gut microbiota increased after fecal microbiota transplantation. Similarly, the relative abundance of the Firmicutes phylum (effect value: 1.44), Ruminococcus genus (effect value: 1.69), and butyrate-producing bacteria increased after fecal microbiota transplantation. Furthermore, fecal microbiota transplantation increased the fecal concentration of butyrate and induced histone acetylation and the mRNA expression of brain-derived neurotrophic factor in the hippocampus, thereby suppressing neuroinflammation and neuronal apoptosis.<br><br>CONCLUSIONS: The alternation of gut microbiota after fecal microbiota transplantation influenced spatial learning ability in neonatal rats with developmental anesthetic neurotoxicity. Modulation of the gut microbiota may be an effective prophylaxis for developmental anesthetic neurotoxicity in children.}, }
@article {pmid39897551, year = {2025}, author = {Yu, C and Sun, R and Yang, W and Gu, T and Ying, X and Ye, L and Zheng, Y and Fan, S and Zeng, X and Yao, S}, title = {Exercise ameliorates osteopenia in mice via intestinal microbial-mediated bile acid metabolism pathway.}, journal = {Theranostics}, volume = {15}, number = {5}, pages = {1741-1759}, pmid = {39897551}, issn = {1838-7640}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Bile Acids and Salts/metabolism ; *Bone Diseases, Metabolic/therapy/metabolism/microbiology ; *Physical Conditioning, Animal/physiology ; Female ; Fecal Microbiota Transplantation/methods ; Mice, Inbred C57BL ; Osteoporosis ; Ovariectomy ; Metabolomics ; Osteogenesis ; Disease Models, Animal ; RNA, Ribosomal, 16S/genetics ; Metabolome ; }, abstract = {Rationale: Physical exercise is essential for skeletal integrity and bone health. The gut microbiome, as a pivotal modulator of overall physiologic states, is closely associated with skeletal homeostasis and bone metabolism. However, the potential role of intestinal microbiota in the exercise-mediated bone gain remains unclear. Methods: We conducted microbiota depletion and fecal microbiota transplantation (FMT) in ovariectomy (OVX) mice and aged mice to investigate whether the transfer of gut ecological traits could confer the exercise-induced bone protective effects. The study analyzed the gut microbiota and metabolic profiles via 16S rRNA gene sequencing and LC-MS untargeted metabolomics to identify key microbial communities and metabolites responsible for bone protection. Transcriptome sequencing and RNA interference were employed to explore the molecular mechanisms. Results: We found that gut microbiota depletion hindered the osteogenic benefits of exercise, and FMT from exercised osteoporotic mice effectively mitigated osteopenia. Comprehensive profiling of the microbiome and metabolome revealed that the exercise-matched FMT reshaped intestinal microecology and metabolic landscape. Notably, alterations in bile acid metabolism, specifically the enrichment of taurine and ursodeoxycholic acid, mediated the protective effects on bone mass. Mechanistically, FMT from exercised mice activated the apelin signaling pathway and restored the bone-fat balance in recipient MSCs. Conclusion: Our study underscored the important role of the microbiota-metabolic axis in the exercise-mediated bone gain, heralding a potential breakthrough in the treatment of osteoporosis.}, }
@article {pmid39897545, year = {2025}, author = {Hou, W and Cao, Y and Wang, J and Yin, F and Wang, J and Guo, N and Wang, Z and Lv, X and Ma, C and Chen, Q and Yang, R and Wei, H and Li, J and Wang, R and Qin, H}, title = {Single-cell nanocapsules of gut microbiota facilitate fecal microbiota transplantation.}, journal = {Theranostics}, volume = {15}, number = {5}, pages = {2069-2084}, pmid = {39897545}, issn = {1838-7640}, mesh = {Animals ; *Nanocapsules/chemistry/administration &amp; dosage ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Mice ; Disease Models, Animal ; Colitis/therapy/microbiology ; Mice, Inbred C57BL ; Humans ; Fibroins/chemistry ; Male ; Phosphatidylcholines/chemistry ; }, abstract = {Rationale: Fecal microbiota transplantation (FMT) is advantageous for treating intractable diseases via the microbiota-gut-organ axis. However, invasive administration of gut microbiota via nasal feeding tubes limits the widespread application of FMT. Here, we attempted to develop a novel strategy to deliver gut microbiota using nanocapsules. Methods: Single-cell nanocapsules were fabricated within 1 h by layer-by-layer assembly of silk fibroin and phosphatidylcholine to generate a protective nanoshell on the cell surface of complicated microbiota. The physical properties of the microbiota nanocapsules were analyzed. The protective effects of nanocapsules on the gastrointestinal tract were analyzed both in vitro and in vivo. The efficacy of FMT assisted by single-cell nanocapsules (NanoFMT) was evaluated using the inflammatory response, gut microbiota balance, and histopathological analysis in animal model. Results: The nanocapsules achieved a good coating ratio for a single type of microbe and complex microbiota, resulting in a remarkable increase in the survival rate of microbes in the gastrointestinal tract. NanoFMT improved the diversity and abundance of the gut microbiota better than common FMT in germ-free mice. Moreover, NanoFMT alleviated intestinal inflammation and positively reversed the microbiota balance in a mouse model of colitis compared with common FMT, assisted by the inherent anti-inflammatory effects of silk fibroin and phosphatidylcholine. Conclusions: Considering its rapid preparation, convenient delivery, and perfect therapeutic effect, we anticipate that NanoFMT may be a promising clinical candidate for next-generation FMT treatment.}, }
@article {pmid39896755, year = {2025}, author = {Zhao, B and Zhou, H and Lin, K and Xu, J and Zhou, B and Xie, D and Ma, J and Yang, L and Su, C and Yang, L}, title = {Antimicrobial peptide DP7 alleviates dextran sulfate sodium (DSS)-induced colitis via modifying gut microbiota and regulating intestinal barrier function.}, journal = {MedComm}, volume = {6}, number = {2}, pages = {e70085}, pmid = {39896755}, issn = {2688-2663}, abstract = {Inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), represent a growing global health concern. Restoring the balance of the gut microbiota, a crucial factor in intestinal health, offers potential for treating IBD. DP7, a novel antimicrobial peptide with potent antibacterial activity, was investigated for its anti-inflammatory effects in a dextran sulfate sodium (DSS)-induced UC mouse model. DP7 significantly ameliorated key disease parameters, including disease activity index, weight loss, and shortened colon length, while preserving colonic epithelial integrity and reducing inflammatory infiltration. Further analysis revealed potential targets of DP7, highlighting the significant role of Muribaculaceae bacteria during inflammatory states. To further explore the role of the gut microbiota in DP7's efficacy, fecal microbiota transplantation (FMT) was performed using feces from DP7-treated mice. FMT successfully ameliorated colitis in recipient mice, providing further evidence for the crucial role of the gut microbiome in IBD treatment and DP7's ability to modulate the gut microbiota for therapeutic benefit. Moreover, our findings suggest that DP7's modulation of the immune system is intricately linked to the complex microbial environment. Our findings demonstrate that DP7 effectively mitigates inflammation, attenuates barrier dysfunction, and shapes the gut microbiota, suggesting its potential as a therapeutic agent for UC.}, }
@article {pmid39896483, year = {2025}, author = {Gray, SM and Wood, MC and Mulkeen, SC and Ahmed, S and Thaker, SD and Chen, B and Sander, WR and Bibeva, V and Zhang, X and Yang, J and Herzog, JW and Zhang, S and Dogan, B and Simpson, KW and Balfour Sartor, R and Montrose, DC}, title = {Dietary protein source mediates colitis pathogenesis through bacterial modulation of bile acids.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39896483}, issn = {2692-8205}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; }, abstract = {Evidence-based dietary recommendations for individuals with inflammatory bowel diseases (IBD) are limited. Red meat consumption is associated with increased IBD incidence and relapse in patients, suggesting that switching to a plant-based diet may limit gut inflammation. However, the mechanisms underlying the differential effects of these diets remain poorly understood. Feeding diets containing plant- or animal-derived proteins to murine colitis models revealed that mice given a beef protein (BP) diet exhibited the most severe colitis, while mice fed pea protein (PP) developed mild inflammation. The colitis-promoting effects of BP were microbially-mediated as determined by bacterial elimination or depletion and microbiota transplant studies. In the absence of colitis, BP-feeding reduced abundance of Lactobacillus johnsonii and Turicibacter sanguinis and expanded Akkermansia muciniphila, which localized to the mucus in association with decreased mucus thickness and quality. BP-fed mice had elevated primary and conjugated fecal bile acids (BAs), and taurocholic acid administration to PP-fed mice worsened colitis. Dietary psyllium protected against BP-mediated inflammation, restored BA-modulating commensals and normalized BA ratios. Collectively, these data suggest that the protein component of red meat may be responsible, in part, for the colitis-promoting effects of this food source and provide insight into dietary factors that may influence IBD severity.}, }
@article {pmid39895632, year = {2025}, author = {Gazzaniga, FS and Kasper, DL}, title = {The gut microbiome and cancer response to immune checkpoint inhibitors.}, journal = {The Journal of clinical investigation}, volume = {135}, number = {3}, pages = {}, pmid = {39895632}, issn = {1558-8238}, mesh = {*Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Humans ; Animals ; *Neoplasms/immunology/therapy/microbiology/drug therapy/pathology ; Mice ; Fecal Microbiota Transplantation ; }, abstract = {Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy, yet only a fraction of patients respond. Remarkably, gut bacteria impact the efficacy of ICIs in fighting tumors outside of the gut. Certain strains of commensal gut bacteria promote antitumor responses to ICIs in a variety of preclinical mouse tumor models. Patients with cancer who respond to ICIs have a different microbiome compared with that of patients who don't respond. Fecal microbiota transplants (FMTs) from patients into mice phenocopy the patient tumor responses: FMTs from responders promote response to ICIs, whereas FMTs from nonresponders do not promote a response. In patients, FMTs from patients who have had a complete response to ICIs can overcome resistance in patients who progress on treatment. However, the responses to FMTs are variable. Though emerging studies indicate that gut bacteria can promote antitumor immunity in the absence of ICIs, this Review will focus on studies that demonstrate relationships between the gut microbiome and response to ICIs. We will explore studies investigating which bacteria promote response to ICIs in preclinical models, which bacteria are associated with response in patients with cancer receiving ICIs, the mechanisms by which gut bacteria promote antitumor immunity, and how microbiome-based therapies can be translated to the clinic.}, }
@article {pmid39895628, year = {2025}, author = {Si, W and Zhao, X and Li, R and Li, Y and Ma, C and Zhao, X and Bugno, J and Qin, Y and Zhang, J and Liu, H and Wang, L}, title = {Lactobacillus rhamnosus GG induces STING-dependent IL-10 in intestinal monocytes and alleviates inflammatory colitis in mice.}, journal = {The Journal of clinical investigation}, volume = {135}, number = {3}, pages = {}, pmid = {39895628}, issn = {1558-8238}, mesh = {Animals ; *Interleukin-10/immunology/genetics ; *Lacticaseibacillus rhamnosus/immunology ; Mice ; *Monocytes/immunology/pathology/metabolism ; *Colitis/immunology/pathology/therapy/genetics/microbiology ; *Membrane Proteins/immunology/genetics/metabolism ; *Probiotics/pharmacology ; Signal Transduction/immunology ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/immunology ; Mice, Knockout ; }, abstract = {Preclinical and clinical observations indicate that the probiotic Lactobacillus rhamnosus GG (LGG) can modulate colonic inflammation. However, the underlying mechanisms have not been explored in depth. Here, we demonstrate that oral administration of live LGG alleviated inflammatory colitis by increasing IL-10 expression in intestinal Ly6C+ monocytes. Mechanistically, LGG induced IL-10 production via the stimulator of IFN genes (STING)/TBK1/NF-κB (RELA) signaling pathway in intestinal Ly6C+ monocytes, enhancing their immune-suppressive function. Elevated IL-10 subsequently activated IL-10 signaling in Ly6C+ monocytes, resulting in an IL-10-based autocrine regulatory loop and inhibition of proinflammatory cytokine production. Furthermore, LGG shifted the gut microbial community and its metabolic functions, leading to intestinal immune responses against colitis. Fecal microbiota transplantation from LGG-colonized mice alleviated immune checkpoint blockade-associated colitis. Our findings highlight the importance of STING signaling in IL-10-dependent antiinflammatory immunity and establish an empirical basis for developing oral administration of live LGG as an efficient and safe therapeutic strategy against inflammatory colitis.}, }
@article {pmid39892949, year = {2025}, author = {McGann, C and Phyu, R and Bittinger, K and Mukhopadhyay, S}, title = {Role of the Microbiome in Neonatal Infection: Pathogenesis and Implications for Management.}, journal = {Clinics in perinatology}, volume = {52}, number = {1}, pages = {147-166}, doi = {10.1016/j.clp.2024.10.010}, pmid = {39892949}, issn = {1557-9840}, mesh = {Humans ; Infant, Newborn ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Neonatal Sepsis/microbiology/therapy ; Anti-Bacterial Agents/therapeutic use ; *Microbiota ; }, abstract = {The human microbiome refers to the collective genome of microorganisms, including bacteria, fungi, and viruses residing on human body surfaces that are in contact with the environment. Together these communities protect against invasive infections. Conversely, when disrupted, the microbiome can be the source of pathogens causing invasive infection. Interventions to manipulate it via probiotics, antibiotics, and fecal transplantation are available. The risk benefit of these interventions remains unclear. In this review, the authors discuss evidence linking the gut microbiome to neonatal sepsis and also discuss the challenges for translating this knowledge into better clinical care.}, }
@article {pmid39890521, year = {2024}, author = {Rafie, E and Zugman, M and Pal, SK and Routy, B and Elkrief, A}, title = {What Is the Role of Fecal Microbiota Transplantation in Immunotherapy Trials? Current Perspectives and Future Directions.}, journal = {European urology focus}, volume = {10}, number = {6}, pages = {882-885}, doi = {10.1016/j.euf.2024.12.009}, pmid = {39890521}, issn = {2405-4569}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Immunotherapy/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; Gastrointestinal Microbiome/immunology ; *Urogenital Neoplasms/therapy/immunology ; Forecasting ; }, abstract = {Immune checkpoint inhibitors (ICIs) are rapidly transforming the treatment landscape of genitourinary and other immunogenic malignancies. Despite these advances, biomarkers for the prediction of ICI response remain to be established. The gut microbiome has been identified as a modulator of immune regulation and a potential regulator of response to ICIs. Fecal microbiota transplantation (FMT) has emerged as a potential novel therapeutic tool to enhance ICI response, as demonstrated in several trials, spanning across genitourinary malignancies as well as others. While safety and clinical potential of FMT have been demonstrated, FMT parameters including optimal treatment regimens, bowel preparation protocols, patient selection, and donor-host compatibility need to be defined. Furthermore, targeted interventions including probiotic supplementation represent promising therapeutic avenues meriting further study.}, }
@article {pmid39889629, year = {2025}, author = {Zhu, W and Hu, Y and Shi, Y and Bao, H and Cheng, X and Jiang, M and Peng, Z and Song, J and Fang, F and Jian, C and Yuan, W and Chen, J and Shu, X}, title = {Sleep deprivation accelerates Parkinson's disease via modulating gut microbiota associated microglial activation and oxidative stress.}, journal = {Microbiological research}, volume = {293}, number = {}, pages = {128077}, doi = {10.1016/j.micres.2025.128077}, pmid = {39889629}, issn = {1618-0623}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Oxidative Stress ; *Microglia/metabolism ; Mice ; *Parkinson Disease/microbiology/etiology ; *Sleep Deprivation/complications/microbiology ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; Disease Progression ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {The interplay between Parkinson's disease (PD) and sleep disturbances suggests that sleep problems constitute a risk factor for PD progression, but the underlying mechanisms remain unclear. Microglial activation and oxidative stress are considered to play an important role in the pathogenesis of aging and neurodegenerative diseases. We hypothesized that sleep deprivation (SD) could exacerbate PD progression via modulating microglial activation and oxidative stress. To test this hypothesis, we established a PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), then subjected the mice to SD. A battery of behavioral tests, including rotarod, pole, adhesive removal, and open field tests, were used to assess motor function. Our study showed that SD exacerbated motor deficits, loss of tyrosine hydroxylase (TH), microglial activation and oxidative stress damage in PD model mice. Fecal microbiota transplantation experiments revealed that SD mediated PD progression, microglial activation and oxidative stress via the gut microbiota. 16S rRNA sequencing analysis indicated that SD increased the abundances of bacteria such as Bacteroidaceae, while decreasing the abundances of bacteria including Lactobacillus. Non-targeted metabolomic analysis of gut microbiota-derived metabolites revealed that SD significantly increased the production of adenosine (ADO), a purine metabolite. Probiotic supplementation reversed the effects of SD on motor deficits, dopaminergic neuron loss, microglial activation and oxidative stress damage in PD mice; it also decreased SD-induced ADO production. Administration of Adenosine A2A receptor (A2AR) inhibitors, Istradefylline (Ist), attenuated the roles of SD and ADO in promoting microglial activation, oxidative stress and PD progression. Taken together, our findings indicate that SD accelerates PD progression via regulating microbiota associated microglial activation and oxidative stress, suggesting that efforts to improve sleep quality can be used to prevent and treat PD.}, }
@article {pmid39887665, year = {2025}, author = {Zeng, X and Sun, L and Xie, H and Gong, S and Lu, C and Xu, Z and Guan, H and Han, B and Wang, W and Zhang, Z and Zhou, J and Wang, S and Chen, Y and Xiao, W}, title = {Lactobacillus johnsonii Generates Cyclo(pro-trp) and Promotes Intestinal Ca[2+] Absorption to Alleviate CKD-SHPT.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {16}, pages = {e2414678}, pmid = {39887665}, issn = {2198-3844}, support = {82270585//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Renal Insufficiency, Chronic/metabolism/complications/microbiology ; *Calcium/metabolism ; Gastrointestinal Microbiome/physiology ; *Hyperparathyroidism, Secondary/metabolism/microbiology/etiology ; *Lactobacillus johnsonii/metabolism ; Male ; *Intestinal Absorption/physiology ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Humans ; Parathyroid Hormone/metabolism ; }, abstract = {Patients with chronic kidney disease (CKD) are at a high risk of developing secondary hyperparathyroidism (SHPT), which may cause organ dysfunction and increase patient mortality. The main clinical interventions for CKD-SHPT involve calcium supplements to boost absorption, but ineffective for some patients, and the reasons remain unclear. Here, CKD mice are divided into high and low groups based on intact parathyroid hormone (iPTH) levels. The high group exhibits significant changes in gut microbes, including a decrease in Lactobacillus, an increase in parathyroid hyperplasia, and a decrease in intestinal calcium. Fecal microbiota transplantation and L. johnsonii colonization indicate a link between gut microbes and CKD-SHPT. Clinically, higher L. johnsonii levels are correlated with milder hyperparathyroidism CKD-SHPT. The receiver operating characteristic (ROC) curve for L. johnsonii abundance and surgical risk is 0.81, with the calibration curve confirming predictive accuracy, and decision curve analysis revealing good clinical applicability. In vivo and in vitro experiments show that cyclo(pro-trp) enhance calcium inflow and lower iPTH levels in intestinal epithelial cells via a calcium-sensing receptor and transient receptor potential vanilloid 4 pathways. This study identified the crucial role of L. johnsonii in CKD-SHPT, unveiling a new mechanism for calcium imbalance and offering novel strategies for SHPT treatment and drug development.}, }
@article {pmid39887373, year = {2025}, author = {Byrd, DA and Damerell, V and Gomez Morales, MF and Hogue, SR and Lin, T and Ose, J and Himbert, C and Ilozumba, MN and Kahlert, C and Shibata, D and Toriola, AT and Li, CI and Figueiredo, J and Stephens, WZ and Warby, CA and Hardikar, S and Siegel, EM and Round, J and Ulrich, CM and Gigic, B}, title = {The gut microbiome is associated with disease-free survival in stage I-III colorectal cancer patients.}, journal = {International journal of cancer}, volume = {157}, number = {1}, pages = {64-73}, doi = {10.1002/ijc.35342}, pmid = {39887373}, issn = {1097-0215}, support = {01KD2101D//German Federal Ministry of Education and Research/ ; R01 AG083580/AG/NIA NIH HHS/United States ; //Stiftung LebensBlicke/ ; //ERA-NET on Translational Cancer Research (TRANSCAN)/ ; //Rahel Goitein-Straus-Program/ ; 01KT1503//German Federal Ministry of Education and Research/ ; //Matthias-Lackas Foundations/ ; U01 CA206110/NH/NIH HHS/United States ; //Heidelberger Stiftung Chirurgie, Heidelberg University Hospital/ ; R01 CA189184/NH/NIH HHS/United States ; //Medizinische Fakult&#xe4;t Heidelberg, Universit&#xe4;t Heidelberg/ ; U01 CA206110/CA/NCI NIH HHS/United States ; R01 CA189184/NH/NIH HHS/United States ; U01 CA206110/NH/NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Colorectal Neoplasms/microbiology/pathology/mortality ; Female ; Male ; Middle Aged ; Aged ; Feces/microbiology ; Disease-Free Survival ; RNA, Ribosomal, 16S/genetics ; Prospective Studies ; Neoplasm Staging ; Bacteria/genetics/classification/isolation &amp; purification ; }, abstract = {Colorectal cancer (CRC) is the second overall leading cause of cancer death in the United States, with recurrence being a frequent cause of mortality. Approaches to improve disease-free survival (DFS) are urgently needed. The gut microbiome, reflected in fecal samples, is likely mechanistically linked to CRC progression and may serve as a non-invasive biomarker. Accordingly, we leveraged baseline fecal samples from N = 166 stage I-III CRC patients in the ColoCare Study, a prospective cohort of newly diagnosed CRC patients. We sequenced the V3 and V4 regions of the 16S rRNA gene to characterize fecal bacteria. We calculated estimates of alpha diversity, beta diversity, and a priori- and exploratory-selected bacterial presence/absence and relative abundance. Associations of microbial metrics with DFS were estimated using multivariable Cox proportional hazards models. We found that alpha diversity was strongly associated with improved DFS, most strongly among rectal cancer patients (Shannon HRrectum = 0.40 95% CI = 0.19, 0.87; p = .02). Overall microbiome composition differences (beta diversity), as characterized by principal coordinate axes, were statistically significantly associated with DFS. Peptostreptococcus was statistically significantly associated with worse DFS (HR = 1.62, 95% CI = 1.13, 2.31; p = .01 per 1-SD) and Order Clostridiales was associated with improved DFS (HR = 0.62, 95% CI = 0.43-0.88; p = .01 per 1-SD). In exploratory analyses, Coprococcus and Roseburia were strongly associated with improved DFS. Overall, higher bacterial diversity and multiple bacteria were strongly associated with DFS. Metagenomic sequencing to elucidate species, gene, and functional level details among larger, diverse patient populations are critically needed to support the microbiome as a biomarker of CRC outcomes.}, }
@article {pmid39887250, year = {2025}, author = {Tang, X and Zeng, T and Deng, W and Zhao, W and Liu, Y and Huang, Q and Deng, Y and Xie, W and Huang, W}, title = {Gut microbe-derived betulinic acid alleviates sepsis-induced acute liver injury by inhibiting macrophage NLRP3 inflammasome in mice.}, journal = {mBio}, volume = {16}, number = {3}, pages = {e0302024}, pmid = {39887250}, issn = {2150-7511}, support = {82302480//MOST | National Natural Science Foundation of China (NSFC)/ ; 2022A1515111071//GDSTC | Natural Science Foundation of Guangdong Province ()/ ; 2022M721503//China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists &amp; inhibitors ; Mice ; *Sepsis/complications ; Betulinic Acid ; *Pentacyclic Triterpenes/metabolism/pharmacology ; *Inflammasomes/metabolism/drug effects ; *Macrophages/drug effects/metabolism/immunology ; Male ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Physical Conditioning, Animal ; Disease Models, Animal ; Liver ; }, abstract = {UNLABELLED: Sepsis-induced acute liver injury (SALI) is a prevalent and life-threatening complication associated with sepsis. The gut microbiota plays a crucial role in the maintenance of health and the development of diseases. The impact of physical exercise on gut microbiota modulation has been well-documented. However, the potential impact of gut microbiome on exercise training-induced protection against SALI remains uncertain. Here, we discovered exercise training ameliorated SALI and systemic inflammation in septic mice. Notably, gut microbiota pre-depletion abolished the protective effects of exercise training in SALI mice. Fecal microbiota transplantation treatment revealed that exercise training-associated gut microbiota contributed to the beneficial effect of exercise training on SALI. Exercise training modulated the metabolism of Ligilactobacillus and enriched betulinic acid (BA) levels in mice. Functionally, BA treatment conferred protection against SALI by inhibiting the hepatic inflammatory response in mice. BA bound and inactivated hnRNPA2B1, thus suppressing NLRP3 inflammasome activation in macrophages. Collectively, this study reveals gut microbiota is involved in the protective effects of exercise training against SALI, and gut microbiota-derived BA inhibits the hepatic inflammatory response via the hnRNPA2B1-NLRP3 axis, providing a potential therapeutic strategy for SALI.<br><br>IMPORTANCE: Sepsis is characterized by a dysregulated immune response to an infection that leads to multiple organ dysfunction. The occurrence of acute liver injury is frequently observed during the initial stage of sepsis and is directly linked to mortality in the intensive care unit. The preventive effect of physical exercise on SALI is well recognized, yet the underlying mechanism remains poorly elucidated. Exercise training alters the gut microbiome in mice, increasing the abundance of Ligilactobacillus and promoting the generation of BA. Additionally, BA supplementation can suppress the NLRP3 inflammasome activation in macrophages by directly binding to hnRNPA2B1, thereby mitigating SALI. These results highlight the beneficial role of gut microbiota-derived BA in inhibiting the hepatic inflammatory response, which represents a crucial stride toward implementing microbiome-based therapeutic strategies for the clinical management of sepsis.}, }
@article {pmid39885417, year = {2025}, author = {Abdel-Raoof Fouda, M and Abdel-Wahhab, M and Abdelkader, AE and Ibrahim, ME and Elsheikh, TA and Aldeweik, HM and Elfeky, N}, title = {Effect of gut microbiota changes on cytokines IL-10 and IL-17 levels in liver transplantation patients.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {140}, pmid = {39885417}, issn = {1471-2334}, mesh = {Humans ; *Liver Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; *Interleukin-17/blood ; Female ; Middle Aged ; *Interleukin-10/blood ; Adult ; Feces/microbiology ; Bacteria/classification/isolation &amp; purification/genetics ; Aged ; Dysbiosis ; }, abstract = {BACKGROUND: Liver transplantation (LT) is a critical intervention for individuals with end-stage liver disease; yet, post-transplant problems, especially infections, graft rejection, and chronic liver disease, are often linked to systemic inflammation. Cytokines, small signaling molecules, significantly influence immune responses during and post-liver transplantation. Nonetheless, the intricate relationships among cytokines, immune responses, and the gut microbiota, especially gut dysbiosis, are still inadequately comprehended. Thus, this study aims to identify the gut microbiota (GM) and determine their relationship to cytokines (IL-17 and IL-10) in LT patients, due to their importance in enhancing the recovery rate.<br><br>RESULT: The research included 31 liver transplant (LT) patients from the Gastroenterology Surgical Center at Mansoura University, resulting in the collection of 174 stool and blood samples from all participants. Fourteen bacterial species have been identified in samples collected at three intervals: one week before, one week post, and two weeks post LT. A change in gut microbiota composition was noted, characterized by a rise in potentially pathogenic bacteria such as Enterococci and Enterobacteriaceae (including Escherichia coli and Klebsiella) and a reduction in beneficial bacteria such as Bacteroidetes and Firmicutes. The examination of patient demographic and clinical data revealed no significant correlations between sex, age, or diagnostic categories and gut microbiota composition. The findings of the Multivariate Analysis of Variance (MANOVA) indicated a substantial effect of gut microbiota composition on cytokine levels (IL-10 and IL-17), with all tests producing p-values of 0.001. The assessment of cytokine levels indicated fluctuating variations at several time points following surgery. IL-10 levels in the GM groups exhibited a statistically significant elevation during the second week post-surgery (p&#x2009;=&#x2009;0.036), suggesting a potential recovery-related anti-inflammatory response. In contrast, IL-17 levels rose in the NI group over time, indicating a transition to a pro-inflammatory condition.<br><br>CONCLUSION: This study emphasizes the pivotal role of the gut microbiota in regulating immune responses following transplantation.}, }
@article {pmid39881980, year = {2024}, author = {Renk, H and Schoppmeier, U and Müller, J and Kuger, V and Neunhoeffer, F and Gille, C and Peter, S}, title = {Oxygenation and intestinal perfusion and its association with perturbations of the early life gut microbiota composition of children with congenital heart disease.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1468842}, pmid = {39881980}, issn = {1664-302X}, abstract = {BACKGROUND: Early life gut microbiota is known to shape the immune system and has a crucial role in immune homeostasis. Only little is known about composition and dynamics of the intestinal microbiota in infants with congenital heart disease (CHD) and potential influencing factors.<br><br>METHODS: We evaluated the intestinal microbial composition of neonates with CHD (n&#x202f;=&#x202f;13) compared to healthy controls (HC, n&#x202f;=&#x202f;30). Fecal samples were analyzed by shotgun metagenomics. Different approaches of statistical modeling were applied to assess the impact of influencing factors on variation in species composition. Unsupervised hierarchical clustering of the microbial composition of neonates with CHD was used to detect associations of distinct clusters with intestinal tissue oxygenation and perfusion parameters, obtained by the "oxygen to see" (O2C) method.<br><br>RESULTS: Overall, neonates with CHD showed an intestinal core microbiota dominated by the genera Enterococcus (27%) and Staphylococcus (20%). Furthermore, a lower abundance of the genera Bacteroides (8% vs. 14%), Parabacteroides (1% vs. 3%), Bifidobacterium (4% vs. 12%), and Escherichia (8% vs. 23%) was observed in CHD compared to HCs. CHD patients that were born by vaginal delivery showed a lower fraction of the genera Bacteroides (15% vs. 21%) and Bifidobacterium (7% vs. 22%) compared to HCs and in those born by cesarean section, these genera were not found at all. In infants with CHD, we found a significant impact of oxygen saturation (SpO2) on relative abundances of the intestinal core microbiota by multivariate analysis of variance (F[8,2]&#x202f;=&#x202f;24.9, p&#x202f;=&#x202f;0.04). Statistical modeling suggested a large proportional shift from a microbiota dominated by the genus Streptococcus (50%) in conditions with low SpO2 towards the genus Enterococcus (61%) in conditions with high SpO2. We identified three distinct compositional microbial clusters, corresponding neonates differed significantly in intestinal blood flow and global gut perfusion.<br><br>CONCLUSION: Early life differences in gut microbiota of CHD neonates versus HCs are possibly linked to oxygen levels. Delivery method may affect microbiota stability. However, further studies are needed to assess the effect of potential interventions including probiotics or fecal transplants on early life microbiota perturbations in neonates with CHD.}, }
@article {pmid39880356, year = {2025}, author = {Wang, S and Yan, K and Dong, Y and Chen, Y and Song, J and Chen, Y and Liu, X and Qi, R and Zhou, X and Zhong, J and Li, J}, title = {The influence of microplastics on hypertension-associated cardiovascular injury via the modulation of gut microbiota.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {368}, number = {}, pages = {125760}, doi = {10.1016/j.envpol.2025.125760}, pmid = {39880356}, issn = {1873-6424}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Microplastics/toxicity ; *Hypertension ; Mice ; Male ; Blood Pressure/drug effects ; Humans ; Feces/chemistry ; }, abstract = {Microplastics (MPs) have been found to interfere with the gut microbiota and compromise the integrity of the gut barrier. Excessive exposure to MPs markedly elevates the risk of cardiovascular disease, yet their influence on hypertension remains elusive, calling for investigation into their potential impacts on blood pressure (BP) regulation. In the present study, an increase in the concentration of MPs was observed in the fecal samples of individuals suffering from hypertension, as compared to the controls. Oral administration of MPs led to obvious increases in systolic, diastolic and mean BP levels in mice. MPs were associated with promoting myocardial hypertrophy, fibrosis, and cardiac remodeling through alterations in gut microbial composition, such as Prevotella and Coprobacillus, or fecal metabolites Betaine and Glycyrrhetinic acid. The hypertensive damage mediated by MPs was significantly mitigated by the high-fiber diet or antibiotics that targeted the gut microbiota. Notablely, fecal microbiota transplantation from mice treated with MPs led to an increase in systolic BP levels and the development of cardiac dysfunction. Our findings offer valuable insights into the complex interplay between MPs and the gut microbiome in the context of hypertension, and suggest potential strategies for reducing the vascular and cardiac injury caused by MPs.}, }
@article {pmid39879970, year = {2025}, author = {Stallmach, A}, title = {[The gastrointestinal microbiome - vision and mission].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {150}, number = {4}, pages = {157-162}, doi = {10.1055/a-2303-3368}, pmid = {39879970}, issn = {1439-4413}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Germany ; Dysbiosis/therapy/microbiology ; }, abstract = {The gastrointestinal microbiome influences physiological functions and is altered in a variety of diseases. The causality of "dysbiosis" in the pathogenesis is not always proven; association studies are often involved. Patients with IBD, bacteria, fungi, bacteriophages, and archaea show disease-typical patterns associated with metabolome disturbances. Fecal microbiome transfer (FMT) for treating various diseases is the subject of numerous clinical studies. Currently, recurrent Clostridioides difficile infection (rCDI) is the only confirmed indication recommended in medical guidelines. In Germany, the FMT is subject to the Medicines Act and may only be carried out as part of individual healing attempts or clinical studies. For patient safety, repeated donor screening, ideally with the construction of a chair bench, is necessary. This significantly limits the nationwide availability of the FMT in Germany. Microbiota-based therapeutics prepared from the stool of tested donors have recently been approved by the US Food and Drug Administration (FDA) for the prevention of rCDI. More microbiome-based medicines can be expected in the future.}, }
@article {pmid39879969, year = {2025}, author = {Weirauch, T and Vehreschild, MJGT}, title = {[Nosocomial gastrointestinal infections and Clostridioides difficile].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {150}, number = {4}, pages = {149-156}, doi = {10.1055/a-2303-3321}, pmid = {39879969}, issn = {1439-4413}, mesh = {Humans ; *Cross Infection/epidemiology/therapy/diagnosis/drug therapy ; *Clostridium Infections/epidemiology/therapy/diagnosis/drug therapy ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Diarrhea/epidemiology/microbiology ; Vancomycin/therapeutic use ; Gastrointestinal Microbiome ; Germany/epidemiology ; }, abstract = {German surveillance data from 2022 reported a prevalence of nosocomial infections among hospitalized patients of 5,2%. Clostridioides-difficile-infections (CDI) are the most frequent cause of nosocomial diarrhea. They are usually caused by antibiotic exposure and the subsequent changes in the gut microbiota. Clinical manifestation ranges from asymptomatic colonization over moderate diarrhea to severe pseudomembranous colitis. According to the current German Gastrointestinal Infection Guidelines, fidaxomicin is the preferred treatment option for CDI, especially in patients at high risk of recurrence or those already suffering from recurrence. Vancomycin can also be used as an alternative for initial CDI treatment. Fecal microbiota transplantation is considered a treatment approach for patients with multiple recurrences.}, }
@article {pmid39879083, year = {2025}, author = {Carroll, A and Bell, MJ and Bleach, ECL and Turner, D and Williams, LK}, title = {Impact of dairy calf management practices on the intestinal tract microbiome pre-weaning.}, journal = {Journal of medical microbiology}, volume = {74}, number = {1}, pages = {}, doi = {10.1099/jmm.0.001957}, pmid = {39879083}, issn = {1473-5644}, mesh = {Animals ; Cattle/microbiology/growth &amp; development ; *Gastrointestinal Microbiome ; Weaning ; *Animal Husbandry/methods ; *Dairying/methods ; }, abstract = {Introduction. Microbiota in the gastrointestinal tract (GIT) consisting of the rumen and hindgut (the small intestine, cecum and colon) in dairy calves play a vital role in their growth and development. This review discusses the development of dairy calf intestinal microbiomes with an emphasis on the impact that husbandry and rearing management have on microbiome development, health and growth of pre-weaned dairy calves.Discussion. The diversity and composition of the microbes that colonize the lower GIT (small and large intestine) can have a significant impact on the growth and development of the calf, through influence on nutrient metabolism, immune modulation, resistance or susceptibility to infection, production outputs and behaviour modification in adult life. The colonization of the calf intestinal microbiome dynamically changes from birth, increasing microbial richness and diversity until weaning, where further dynamic and drastic microbiome change occurs. In dairy calves, neonatal microbiome development prior to weaning is influenced by direct and indirect factors, some of which could be considered stressors, such as maternal interaction, environment, diet, husbandry and weaning practices. The specific impact of these can dictate intestinal microbial colonization, with potential lifelong consequences.Conclusion. Evidence suggests the potential detrimental effect that sudden changes and stress may have on calf health and growth due to management and husbandry practices, and the importance of establishing a stable yet diverse intestinal microbiome population at an early age is essential for calf success. The possibility of improving the health of calves through intestinal microbiome modulation and using alternative strategies including probiotic use, faecal microbiota transplantation and novel approaches of microbiome tracking should be considered to support animal health and sustainability of dairy production systems.}, }
@article {pmid39878866, year = {2025}, author = {Zheng, Y and Yu, Y and Chen, M and Zhang, H and Wang, W and Fan, X and Sun, L and Tang, L and Ta, D}, title = {Abdominal LIPUS Stimulation Prevents Cognitive Decline in Hind Limb Unloaded Mice by Regulating Gut Microbiota.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39878866}, issn = {1559-1182}, abstract = {Weightlessness usually causes disruption of the gut microbiota and impairs cognitive function. There is a close connection between gut microbiota and neurological diseases. Low-intensity pulsed ultrasound (LIPUS) has a beneficial effect on reducing intestinal inflammation. So we wondered if abdominal LIPUS stimulation can have a positive impact on weightlessness induced cognitive decline by reducing intestinal dysfunction. The findings revealed that the hind limb unloaded mice exhibited evident disruption in intestinal structure and gut microbial homeostasis, along with impairment in their learning and memory capabilities. However, 4-week abdominal LIPUS treatment improved intestinal function in hind limb unloaded mice, characterized by upregulation of tight junction proteins ZO-1 and Occludin expression in the colon, increased diversity and abundance of intestinal microbiota, decreased serum lipopolysaccharide (LPS), and increased short chain fatty acids in colon contents. The hind limb unloaded mice treated with LIPUS exhibited heightened activity levels, improved exploratory tendencies, and significantly enhanced learning and memory faculties, and elevated expression of neuroadaptation-related proteins such as PSD95, GAP43, P-CREB, BDNF, and its receptor TRKB in the hippocampus. Furthermore, the hind limb unloaded mice receiving fecal transplants from the mice whose abdomens were irradiated with LIPUS displayed enhanced cognitive abilities and improved intestinal structure, akin to the outcomes observed in hind limb unloaded mice who received LIPUS abdominal treatment directly. The above results indicate that LIPUS enhances intestinal structure and microbiota, which helps alleviate cognitive impairment caused by weightlessness. LIPUS could be a potential strategy to simultaneously improve gut dysfunction and cognitive decline in astronauts or bedridden patients.}, }
@article {pmid39875017, year = {2025}, author = {Qin, L and Fan, B and Zhou, Y and Zheng, J and Diao, R and Wang, F and Liu, J}, title = {Targeted gut microbiome therapy: Applications and prospects of probiotics, fecal microbiota transplantation and natural products in the management of type 2 diabetes.}, journal = {Pharmacological research}, volume = {213}, number = {}, pages = {107625}, doi = {10.1016/j.phrs.2025.107625}, pmid = {39875017}, issn = {1096-1186}, mesh = {Humans ; *Diabetes Mellitus, Type 2/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; *Probiotics/therapeutic use ; Animals ; *Biological Products/therapeutic use ; }, abstract = {Type 2 diabetes mellitus (T2DM) is considered as one of the most pressing public health challenges worldwide. Studies have shown significant differences in the gut microbiota between healthy individuals and T2DM patients, suggesting that gut microorganisms may play a key role in the onset and progression of T2DM. This review systematically summarizes the relationship between gut microbiota and T2DM, and explores the mechanisms through which gut microorganisms may alleviate T2DM. Additionally, it evaluates the potential of probiotics, fecal microbiota transplantation (FMT)/virome transplantation (FVT), and natural products in modulating gut microbiota to treat T2DM. Although existing studies have suggested that these interventions may delay or even halt the progression of T2DM, most research remained limited to animal models and observational clinical studies, with a lack of high-quality clinical data. This has led to an imbalance between theoretical research and clinical application. Although some studies have explored the regulatory role of the gut virome on the gut microbiota, research in this area remains in its early stages. Based on these current studies, future research should be focused on large-scale, long-term clinical studies and further investigation on the potential role of the gut virome in T2DM. In conclusion, this review aims to summarize the current evidence and explore the applications of gut microbiota in T2DM treatment, as well as providing recommendations for further investigation in this field.}, }
@article {pmid39874238, year = {2025}, author = {Scher, JU and Nayak, R and Clemente, JC}, title = {Microbiome research in autoimmune and immune-mediated inflammatory diseases: lessons, advances and unmet needs.}, journal = {Annals of the rheumatic diseases}, volume = {84}, number = {1}, pages = {9-13}, pmid = {39874238}, issn = {1468-2060}, support = {R01 AR074500/AR/NIAMS NIH HHS/United States ; T32 AR069515/AR/NIAMS NIH HHS/United States ; UC2 AR081034/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; *Autoimmune Diseases/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/immunology/microbiology ; Fecal Microbiota Transplantation ; Arthritis, Rheumatoid/microbiology/immunology ; Lupus Erythematosus, Systemic/microbiology/immunology ; *Microbiota/immunology ; Inflammation/microbiology/immunology ; *Immune System Diseases/microbiology/immunology ; }, abstract = {The increasing prevalence of autoimmune and immune-mediated diseases (AIMDs) underscores the need to understand environmental factors that contribute to their pathogenesis, with the microbiome emerging as a key player. Despite significant advancements in understanding how the microbiome influences physiological and inflammatory responses, translating these findings into clinical practice remains challenging. This viewpoint reviews the progress and obstacles in microbiome research related to AIMDs, examining molecular techniques that enhance our understanding of microbial contributions to disease. We discuss significant discoveries linking specific taxa and metabolites to diseases such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis, highlighting the role of gut dysbiosis and host-microbiome interactions. Furthermore, we explore the potential of microbiome-based therapeutics, including faecal microbiota transplantation and pharmacomicrobiomics, while addressing the challenges of identifying robust microbial targets. We advocate for integrative, transdisease studies and emphasise the need for diverse cohort research to generalise findings across populations. Understanding the microbiome's role in AIMDs will pave the way for personalised medicine and innovative therapeutic strategies.}, }
@article {pmid39873952, year = {2025}, author = {Pezeshki, B and Abdulabbas, HT and Alturki, AD and Mansouri, P and Zarenezhad, E and Nasiri-Ghiri, M and Ghasemian, A}, title = {Synergistic Interactions Between Probiotics and Anticancer Drugs: Mechanisms, Benefits, and Challenges.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39873952}, issn = {1867-1314}, abstract = {Research into the role of probiotics-often referred to as "living supplements"-in cancer therapy is still in its early stages, and uncertainties regarding their effectiveness remain. Relevantly, chemopreventive and therapeutic effects of probiotics have been determined. There is also substantial evidence supporting their potential in cancer treatment such as immunotherapy. Probiotics employ various mechanisms to inhibit cancer initiation and progression. These include colonizing and protecting the gastrointestinal tract (GIT), producing metabolites, inducing apoptosis and autophagy, exerting anti-inflammatory properties, preventing metastasis, enhancing the effectiveness of immune checkpoint inhibitors (ICIs), promoting cancer-specific T cell infiltration, arresting the cell cycle, and exhibiting direct or indirect synergistic effects with anticancer drugs. Additionally, probiotics have been shown to activate tumor suppressor genes and inhibit pro-inflammatory transcription factors. They also increase reactive oxygen species production within cancer cells. Synergistic interactions between probiotics and various anticancer drugs, such as cisplatin, cyclophosphamide, 5-fluorouracil, trastuzumab, nivolumab, ipilimumab, apatinib, gemcitabine, tamoxifen, sorafenib, celecoxib and irinotecan have been observed. The combination of probiotics with anticancer drugs holds promise in overcoming drug resistance, reducing recurrence, minimizing side effects, and lowering treatment costs. In addition, fecal microbiota transplantation (FMT) and prebiotics supplementation has increased cytotoxic T cells within tumors. However, probiotics may leave some adverse effects such as risk of infection and gastrointestinal effects, antagonistic effects with drugs, and different responses among patients. These findings highlight insights for considering specific strains and engineered probiotic applications, preferred doses and timing of treatment, and personalized therapies to enhance the efficacy of cancer therapy. Accordingly, targeted interventions and guidelines establishment needs extensive randomized controlled trials as probiotic-based cancer therapy has not been approved by Food and Drug Administration (FDA).}, }
@article {pmid39873191, year = {2025}, author = {An, L and Li, S and Chang, Z and Lei, M and He, Z and Xu, P and Zhang, S and Jiang, Z and Iqbal, MS and Sun, X and Liu, H and Duan, X and Wu, W}, title = {Gut microbiota modulation via fecal microbiota transplantation mitigates hyperoxaluria and calcium oxalate crystal depositions induced by high oxalate diet.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2457490}, pmid = {39873191}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Hyperoxaluria/therapy/metabolism/microbiology ; *Fecal Microbiota Transplantation ; *Calcium Oxalate/metabolism/chemistry ; Rats ; *Oxalates/metabolism ; Male ; Rats, Sprague-Dawley ; Disease Models, Animal ; Diet/adverse effects ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Kidney/pathology/metabolism ; }, abstract = {Hyperoxaluria, including primary and secondary hyperoxaluria, is a disorder characterized by increased urinary oxalate excretion and could lead to recurrent calcium oxalate kidney stones, nephrocalcinosis and eventually end stage renal disease. For secondary hyperoxaluria, high dietary oxalate (HDOx) or its precursors intake is a key reason. Recently, accumulated studies highlight the important role of gut microbiota in the regulation of oxalate homeostasis. However, the underlying mechanisms involving gut microbiota and metabolite disruptions in secondary hyperoxaluria remain poorly understood. Here, we investigated the therapeutic efficacy of fecal microbiota transplantation (FMT) sourced from healthy rats fed with standard pellet diet against urinary oxalate excretion, renal damage and calcium oxalate (CaOx) crystal depositions via using hyperoxaluria rat models. We observed dose-dependent increases in urinary oxalate excretion and CaOx crystal depositions due to hyperoxaluria, accompanied by significant reductions in gut microbiota diversity characterized by shifts in Ruminococcaceae_UCG-014 and Parasutterella composition. Metabolomic analysis validated these findings, revealing substantial decreases in key metabolites associated with these microbial groups. Transplanting microbes from healthy rats effectively reduced HDOx-induced urinary oxalate excretion and CaOx crystal depositions meanwhile restoring Ruminococcaceae_UCG-014 and Parasutterella populations and their associated metabolites. Furthermore, FMT treatment could significantly decrease the urinary oxalate excretion and CaOx crystal depositions in rat kidneys via, at least in part, upregulating the expressions of intestinal barrier proteins and oxalate transporters in the intestine. In conclusion, our study emphasizes the effectiveness of FMT in countering HDOx-induced hyperoxaluria by restoring gut microbiota and related metabolites. These findings provide insights on the complex connection between secondary hyperoxaluria caused by high dietary oxalate and disruptions in gut microbiota, offering promising avenues for targeted therapeutic strategies.}, }
@article {pmid39870907, year = {2025}, author = {Misselwitz, B and Haller, D}, title = {[The intestinal microbiota in inflammatory bowel diseases].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {66}, number = {2}, pages = {146-155}, pmid = {39870907}, issn = {2731-7099}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Inflammatory Bowel Diseases/microbiology/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Dysbiosis/therapy ; }, abstract = {BACKGROUND: The intestinal microbiota comprises all living microorganisms in the gastrointestinal tract and is crucial for its function. Clinical observations and laboratory findings confirm a central role of the microbiota in chronic inflammatory bowel diseases (IBD). However, many mechanistic details remain unclear.<br><br>OBJECTIVES: Changes in the microbiota and the causal relationship with the pathogenesis of IBD are described and current and future diagnostic and therapeutic options are discussed.<br><br>MATERIALS AND METHODS: Narrative review.<br><br>RESULTS: The intestinal microbiota is altered in composition, diversity, and function in IBD patients, but specific (universal) IBD-defining bacteria have not been identified. The healthy microbiota has numerous anti-inflammatory functions such as the production of short-chain fatty acids or competition with pathogens. In contrast, the IBD microbiota promotes inflammation through the destruction of the intestinal barrier and direct interaction with the immune system. The balance between pro- and anti-inflammatory effects of the microbiota appears to be crucial for the development of intestinal inflammation. Microbiota-based IBD diagnostics show promise but are not yet ready for clinical use. Probiotics and fecal microbiota transplantation have clinical effects, especially in ulcerative colitis, but the potential of microbiota-based therapies is far from being fully realized.<br><br>CONCLUSION: IBD dysbiosis remains undefined so far. It is unclear how the many parallel pro- and anti-inflammatory mechanisms contribute to IBD pathogenesis. An inadequate mechanistic understanding hinders the development of microbiota-based diagnostics and therapies.}, }
@article {pmid39870349, year = {2025}, author = {Vázquez-Cuesta, S and Olmedo, M and Kestler, M and Álvarez-Uría, A and De la Villa, S and Alcalá, L and Marín, M and Rodríguez-Fernández, S and Sánchez-Martínez, C and Muñoz, P and Bouza, E and Reigadas, E}, title = {Prospective analysis of biomarkers associated with successful faecal microbiota transplantation in recurrent Clostridioides difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2025.01.026}, pmid = {39870349}, issn = {1469-0691}, abstract = {OBJECTIVES: Faecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection (CDI). This study aimed to identify calprotectin and microbiome characteristics as potential biomarkers of FMT success.<br><br>METHODS: We conducted a prospective study of patients who underwent oral FMT (single dose of 4-5 capsules) for recurrent CDI (January 2018 to December 2022). Samples were collected at three time points: at CDI diagnosis, within 24&#xa0;hours before FMT administration, and 30&#xa0;days post-FMT. Calprotectin levels were assessed and the V4 region of the 16S rRNA gene was sequenced to analyse the microbiota composition. Sequencing data analysis and statistical analysis were performed using MOTHUR and R.<br><br>RESULTS: Ninety-seven patients underwent FMT (totalling 105 procedures). A total of 221 samples were processed, including 21 donor samples, 24 capsule contents, and 176 patient faecal samples (39 at diagnosis, 63 pre-FMT, and 74 post-FMT). FMT achieved an overall success rate of 85.1% (86/101 cases). The abundance of Bacteroides, Ruminococcus, Megamonas, and certain Prevotella operational taxonomic units was significantly higher in capsules associated with 100% success compared with less effective capsules. FMT engraftment was observed in 95% of patients with favourable outcomes versus 62% of those with recurrences (p 0.006). Additionally, a negative correlation was found between calprotectin levels and specific microbial genera, suggesting an association with successful outcomes.<br><br>DISCUSSION: This study highlights differences in the evolution of faecal microbiota, bacterial engraftment, and inflammation markers (e.g. calprotectin) between patients with varying FMT outcomes. Potential biomarkers for successful FMT were identified, providing valuable insights for optimizing FMT strategies.}, }
@article {pmid39870263, year = {2025}, author = {Ren, P and Liu, M and Wei, B and Tang, Q and Wang, Y and Xue, C}, title = {Fucoidan exerts antitumor effects by regulating gut microbiota and tryptophan metabolism.}, journal = {International journal of biological macromolecules}, volume = {300}, number = {}, pages = {140334}, doi = {10.1016/j.ijbiomac.2025.140334}, pmid = {39870263}, issn = {1879-0003}, mesh = {*Tryptophan/metabolism ; *Polysaccharides/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Animals ; Mice ; *Antineoplastic Agents/pharmacology ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Kynurenine/blood ; }, abstract = {Fucoidan, a water-soluble polysaccharide derived from marine organisms, has garnered significant attention for its ability to regulate gut microbiota and its anti-tumor properties. However, the existence of a correlation between the anti-tumor effect of fucoidan and its regulation of the gut microbiota remains unknown. In pursuit of this objective, we culled the gut microbiota of mice with broad-spectrum antibiotics to generate pseudo-sterile tumor-bearing mice. Subsequently, fecal microbial transplants were introduced into the pseudo-sterile tumor-bearing mice. The antitumor effects of fucoidan were found to be dependent on the gut microbiota. Fucoidan promoted the proliferation of Akkermansia, Bifidobacterium and Lactobacillus, which have immunomodulatory effects. Furthermore, through regulation of gut microbiota, fucoidan influenced the metabolic process of tryptophan and facilitated its conversion to indole-3-acetic acid. In addition, fucoidan decreased the kynurenine/tryptophan ratio in serum, increased the proportion of CD8+ T cells, and suppressed the expression level of IDO1 in tumor tissues. Our results confirm that fucoidan enhances anti-tumor immune responses and subsequently exhibits anti-tumor effects by modulating the gut microbiota. Our research contributes to the comprehension of the mechanism of anti-tumor effects of fucoidan and facilitates the development of fucoidan as a dietary supplement for cancer patients.}, }
@article {pmid39869016, year = {2025}, author = {Martin Fuentes, A}, title = {The role of the microbiome in skin cancer development and treatment.}, journal = {Current opinion in oncology}, volume = {37}, number = {2}, pages = {121-125}, doi = {10.1097/CCO.0000000000001120}, pmid = {39869016}, issn = {1531-703X}, mesh = {Humans ; *Skin Neoplasms/microbiology/immunology/therapy ; *Microbiota/immunology ; Probiotics/therapeutic use ; *Melanoma/microbiology/immunology/therapy ; Immune Checkpoint Inhibitors/therapeutic use ; Prebiotics ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation ; Animals ; Immunotherapy/methods ; }, abstract = {PURPOSE OF REVIEW: Recent research underscores the significant influence of the skin and gut microbiota on melanoma and nonmelanoma skin cancer (NMSC) development and treatment outcomes. This review aims to synthesize current findings on how microbiota modulates immune responses, particularly enhancing the efficacy of immunotherapies such as immune checkpoint inhibitors (ICIs).<br><br>RECENT FINDINGS: The microbiota's impact on skin cancer is multifaceted, involving immune modulation, inflammation, and metabolic interactions. Beneficial strains like Bifidobacterium and Lactobacillus have shown potential in supporting anti-PD-1 and anti-CTLA-4 therapies by promoting T-cell activation and immune surveillance. Evidence from preclinical and clinical studies, including fecal microbiota transplantation (FMT), highlights improved response rates in patients with microbiota-rich profiles. Notably, certain bacterial metabolites, such as inosine, contribute to enhanced antitumor activity by stimulating IFN-&#x3b3; in CD8 + T cells.<br><br>SUMMARY: Understanding the interplay between microbiota and skin cancer treatment opens promising avenues for adjunctive therapies. Probiotic and prebiotic interventions, FMT, and microbiota modulation are emerging as complementary strategies to improve immunotherapy outcomes and address treatment resistance in melanoma and NMSC.}, }
@article {pmid39868555, year = {2025}, author = {Chatterjee, J and Qi, X and Mu, R and Li, X and Eligator, T and Ouyang, M and Bozeman, SL and Rodgers, R and Aggarwal, S and Campbell, DE and Schriefer, LA and Baldridge, MT and Gutmann, DH}, title = {Intestinal Bacteroides drives glioma progression by regulating CD8+ T cell tumor infiltration.}, journal = {Neuro-oncology}, volume = {}, number = {}, pages = {}, doi = {10.1093/neuonc/noaf024}, pmid = {39868555}, issn = {1523-5866}, abstract = {BACKGROUND: The intestinal microbiota regulates normal brain physiology and the pathogenesis of several neurological disorders. While prior studies suggested that this regulation operates through immune cells, the underlying mechanisms remain unclear. Leveraging two well characterized murine models of low-grade glioma (LGG) occurring in the setting of the neurofibromatosis type 1 (NF1) cancer predisposition syndrome, we sought to determine the impact of the gut microbiome on optic glioma progression.<br><br>METHODS: Nf1-mutant mice genetically engineered to develop optic pathway gliomas (Nf1OPG mice) by 3 months of age were reared under germ-free (GF) conditions, treated with specific cocktails of antibiotics, or given fecal matter transplants (FMTs). Intestinal microbial species were identified by 16S genotyping. Neutralizing TGF&#x3b2; antibodies were delivered systemically, while in vitro experiments used isolated murine microglia and T cells. Single cell RNA sequencing analysis was performed using established methods.<br><br>RESULTS: Nf1 OPG mice raised in a GF environment or postnatally treated with vancomycin did not harbor optic gliomas or exhibit OPG-induced retinal nerve fiber layer thinning, which was reversed following conventionally raised mouse FMT or colonization with Bacteroides species. Moreover, this intestinal microbiota-regulated gliomagenesis was mediated by circulating TGF&#x3b2;, such that systemic TGF&#x3b2; neutralization reduced Nf1-OPG growth. TGF&#x3b2; was shown to act on tumor-associated monocytes to induce Ccl3 expression and recruit CD8+ T cells necessary for glioma growth.<br><br>CONCLUSIONS: Taken together, these findings establish, for the first time, a mechanistic relationship between Bacteroides in the intestinal microbiome and NF1-LGG pathobiology, suggesting both future predictive risk assessment strategies and therapeutic opportunities.}, }
@article {pmid39868290, year = {2025}, author = {Weagley, J and Makimaa, H and Cárdenas, LAC and Romani, A and Sullender, M and Aggarwal, S and Hogarty, M and Rodgers, R and Kennedy, E and Foster, L and Schriefer, LA and Baldridge, MT}, title = {Dynamics of Bacterial and Viral Transmission in Experimental Microbiota Transplantation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39868290}, issn = {2692-8205}, support = {F31 AI167499/AI/NIAID NIH HHS/United States ; R01 AI139314/AI/NIAID NIH HHS/United States ; R01 AI173360/AI/NIAID NIH HHS/United States ; T32 AI007172/AI/NIAID NIH HHS/United States ; }, abstract = {Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transplantation of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of fecal or cecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, fecal transplantation, and cecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored microbial populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR, and shotgun sequencing of viral-like particles. As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transplanted control mice. While all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. This study provides valuable insights into microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transplantation in mouse models.}, }
@article {pmid39864578, year = {2025}, author = {Attiq, A}, title = {Early-life antibiotic exposures: Paving the pathway for dysbiosis-induced disorders.}, journal = {European journal of pharmacology}, volume = {991}, number = {}, pages = {177298}, doi = {10.1016/j.ejphar.2025.177298}, pmid = {39864578}, issn = {1879-0712}, mesh = {Humans ; *Dysbiosis/chemically induced/microbiology ; *Anti-Bacterial Agents/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Animals ; Probiotics ; }, abstract = {Microbiota encompasses a diverse array of microorganisms inhabiting specific ecological niches. Gut microbiota significantly influences physiological processes, including gastrointestinal motor function, neuroendocrine signalling, and immune regulation. They play a crucial role in modulating the central nervous system and bolstering body defence mechanisms by influencing the proliferation and differentiation of innate and adaptive immune cells. Given the potential consequences of antibiotic therapy on gut microbiota equilibrium, there is a need for prudent antibiotic use to mitigate associated risks. Observational studies have linked increased antibiotic usage to various pathogenic conditions, including obesity, inflammatory bowel disease, anxiety-like effects, asthma, and pulmonary carcinogenesis. Addressing dysbiosis incidence requires proactive measures, including prophylactic use of β-lactamase drugs (SYN-004, SYN-006, and SYN-007), hydrolysing the β-lactam in the proximal GIT for maintaining intestinal flora homeostasis. Prebiotic and probiotic supplementations are crucial in restoring intestinal flora equilibrium by competing with pathogenic bacteria for nutritional resources and adhesion sites, reducing luminal pH, neutralising toxins, and producing antimicrobial agents. Faecal microbiota transplantation (FMT) shows promise in restoring gut microbiota composition. Rational antibiotic use is essential to preserve microflora and improve patient compliance with antibiotic regimens by mitigating associated side effects. Given the significant implications on gut microbiota composition, concerted intervention strategies must be pursued to rectify and reverse the occurrence of antibiotic-induced dysbiosis. Here, antibiotics-induced microbiota dysbiosis mechanisms and their systemic implications are reviewed. Moreover, proposed interventions to mitigate the impact on gut microflora are also discussed herein.}, }
@article {pmid39863610, year = {2025}, author = {Reddi, S and Senyshyn, L and Ebadi, M and Podlesny, D and Minot, SS and Gooley, T and Kabage, AJ and Hill, GR and Lee, SJ and Khoruts, A and Rashidi, A}, title = {Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1034}, pmid = {39863610}, issn = {2041-1723}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; ACT9016-24//Leukemia and Lymphoma Society (Leukemia &amp; Lymphoma Society)/ ; }, mesh = {Humans ; *Graft vs Host Disease/prevention &amp; control/microbiology ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Adult ; Middle Aged ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Double-Blind Method ; Tissue Donors ; Transplantation, Homologous/adverse effects ; Young Adult ; Treatment Outcome ; Feces/microbiology ; Acute Disease ; }, abstract = {Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase. The primary and key secondary endpoints were microbiota engraftment and severe aGVHD, respectively. Three cohorts of patients (20 total) received FMT, each from a different donor. FMT was safe and effective in restoring microbiota diversity and commensal species. Microbiota engraftment, determined from shotgun sequencing data, correlated with larger microbiota compositional shifts toward donor and better clinical outcomes. Donor 3 yielded a median engraftment rate of 66%, higher than donors 1 (P = 0.02) and 2 (P = 0.03) in multivariable analysis. Three patients developed severe aGVHD; all 3 had received FMT from donor 1. Donor 3 was selected as the sole donor for the randomized phase. Our findings suggest a clinically relevant donor effect and demonstrate feasibility of evidence-based donor selection. FMT is a holistic microbiota restoration approach that can be performed as a precision therapeutic. ClinicalTrials.gov identifier NCT06026371.}, }
@article {pmid39863438, year = {2025}, author = {Jin, J and Cai, X and Rao, P and Xu, J and Li, J}, title = {Microbiota and immune dynamics in rheumatoid arthritis: Mechanisms and therapeutic potential.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {39}, number = {1}, pages = {102035}, doi = {10.1016/j.berh.2025.102035}, pmid = {39863438}, issn = {1532-1770}, mesh = {Humans ; *Arthritis, Rheumatoid/immunology/microbiology/therapy ; *Dysbiosis/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Rheumatoid arthritis (RA) is a complex autoimmune disease with growing evidence implicating the microbiota as a critical contributor to its pathogenesis. This review explores the multifaceted roles of microbial dysbiosis in RA, emphasizing its impact on immune cell modulation, autoantibody production, gut barrier integrity, and joint inflammation. Animal models reveal how genetic predisposition and environmental factors interact with specific microbial taxa to influence disease susceptibility. Dysbiosis-driven metabolic disruptions, including alterations in short-chain fatty acids and bile acids, further exacerbate immune dysregulation and systemic inflammation. Emerging therapeutic strategies-probiotics, microbial metabolites, fecal microbiota transplantation, and antibiotics-offer innovative avenues for restoring microbial balance and mitigating disease progression. By integrating microbiota-targeted approaches with existing treatments, this review highlights the potential to revolutionize RA management through precision medicine and underscores the need for further research to harness the microbiota's therapeutic potential.}, }
@article {pmid39863236, year = {2025}, author = {Qin, N and Liu, H and Wang, X and Liu, Y and Chang, H and Xia, X}, title = {Sargassum fusiforme polysaccharides protect mice against Citrobacter rodentium infection via intestinal microbiota-driven microRNA-92a-3p-induced Muc2 production.}, journal = {International journal of biological macromolecules}, volume = {300}, number = {}, pages = {140271}, doi = {10.1016/j.ijbiomac.2025.140271}, pmid = {39863236}, issn = {1879-0003}, mesh = {Animals ; *MicroRNAs/genetics/metabolism ; *Mucin-2/metabolism/genetics/biosynthesis ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Sargassum/chemistry ; *Polysaccharides/pharmacology/chemistry ; *Citrobacter rodentium/drug effects ; *Enterobacteriaceae Infections/microbiology/prevention &amp; control/drug therapy/genetics ; Intestinal Mucosa/drug effects/microbiology/metabolism ; Male ; Signal Transduction/drug effects ; Dysbiosis ; Mice, Inbred C57BL ; Edible Seaweeds ; Receptor, Notch1 ; }, abstract = {Sargassum fusiforme, widely consumed in Asian countries, has been proven to have various biological activities. However, the impacts and mechanisms of Sargassum fusiforme polysaccharides (SFPs) on intestinal bacterial infection are not yet fully understood. Our findings indicate that SFPs pretreatment ameliorates intestinal inflammation by reducing C. rodentium colonization, increasing colon length and levels of IL-10 and IL-22, decreasing IL-1β, IL-6, TNF-α, and IL-17 levels, inhibiting colonic crypt elongation and hyperplasia, and enhancing the intestinal mucosal barrier. The protective effects against intestinal bacterial infection are linked to enhanced clearance of C. rodentium and improvements in the intestinal mucosal barrier and C. rodentium-induced intestinal microbiota dysbiosis. Fecal microbiota transplantation experiments were conducted to evaluate the functional impact of microbiota induced by SFPs. The results suggest that intestinal microbiota modified by SFPs effectively countered C. rodentium infection. In addition, our study identified that miRNA-92a-3p is partially complementary to the 3'-UTR of the Notch1 gene, thereby repressing the Notch1-Hes1 signaling pathway and enhancing Muc2 secretion. Taken together, these findings reveal that SFPs protect mice from C. rodentium infection by activating the miR-92a-3p/Notch1-Hes1 regulatory axis driven by the intestinal microbiota, which stimulates Muc2 production to maintain intestinal barrier homeostasis.}, }
@article {pmid39862968, year = {2025}, author = {Huang, P and Di, L and Cui, S and Wang, X and Cao, T and Jiang, S and Huang, L}, title = {Postoperative delirium after cardiac surgery associated with perioperative gut microbiota dysbiosis: Evidence from human and antibiotic-treated mouse model.}, journal = {Anaesthesia, critical care &amp; pain medicine}, volume = {44}, number = {2}, pages = {101484}, doi = {10.1016/j.accpm.2025.101484}, pmid = {39862968}, issn = {2352-5568}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Dysbiosis/microbiology/complications ; Animals ; Humans ; Male ; Mice ; Aged ; Female ; *Anti-Bacterial Agents/therapeutic use ; Middle Aged ; Case-Control Studies ; *Delirium/etiology/microbiology ; *Postoperative Complications/microbiology/etiology ; *Cardiac Surgical Procedures/adverse effects ; Fatty Acids, Volatile/metabolism/analysis ; Fecal Microbiota Transplantation ; Feces/microbiology/chemistry ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Research links gut microbiota to postoperative delirium (POD) through the gut-brain axis. However, changes in gut microbiota and fecal short-chain fatty acids (SCFAs) in POD patients during the perioperative period and their association with POD are unclear.<br><br>METHODS: We conducted a nested case-control study among patients undergoing off-pump coronary artery bypass grafting, focusing on POD as the main outcome. POD patients were matched 1:1 with non-POD patients based on sociodemographic characteristics, health, and diet. Fecal samples were collected pre- and post-surgery to assess gut microbiota and SCFAs changes. Postoperative fecal samples were transplanted into antibiotic-treated mice to evaluate delirium-like behavior and neuroinflammation.<br><br>RESULTS: Out of 120 patients, 60 were matched. Before surgery, gut microbiota in both groups was similar. After surgery, POD patients had lower alpha diversity and distinct microbiota compared to non-POD patients. LEfSe analysis showed POD was linked to increased opportunistic pathogens (Enterococcus) and decreased SCFAs producers (Bacteroides, Ruminococcus, etc.). SCFAs were significantly reduced in POD patients and negatively correlated with delirium severity and plasma inflammation. Mice receiving fecal transplants from POD patients exhibited delirium-like behavior and neuroinflammation.<br><br>CONCLUSIONS: Postoperative delirium is associated with gut microbiota dysbiosis, marked by an increase in opportunistic pathogens and a decrease in SCFA-producing genera.<br><br>REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300070477.}, }
@article {pmid39862808, year = {2025}, author = {Xiao, Y and He, X and Zhang, H and Wu, X and Ai, R and Xu, J and Wen, Q and Zhang, F and Cui, B}, title = {Washed microbiota transplantation effectively improves nutritional status in gastrointestinal disease-related malnourished children.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {132}, number = {}, pages = {112679}, doi = {10.1016/j.nut.2024.112679}, pmid = {39862808}, issn = {1873-1244}, mesh = {Humans ; Male ; Female ; *Nutritional Status ; Prospective Studies ; Child, Preschool ; *Gastrointestinal Diseases/complications/therapy/microbiology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods/adverse effects ; Infant ; Treatment Outcome ; Child ; *Child Nutrition Disorders/therapy/etiology ; *Malnutrition/therapy/etiology ; Dysbiosis/therapy ; }, abstract = {BACKGROUND AND AIM: Gut microbiota dysbiosis plays a critical role in malnutrition caused by food intolerance and intestinal inflammation in children, which needs to be addressed. We assessed the efficacy and safety of washed microbiota transplantation (WMT) for gastrointestinal disease-related malnourished children.<br><br>METHODS: This was a prospective observational study involving gastrointestinal disease-related malnourished pediatric patients who underwent WMT. The primary outcome was the clinical response rate at 3 mo post-WMT. Clinical response was defined as an improvement in the children's nutritional status of one level or more. The secondary outcomes were changes in gastrointestinal symptoms, laboratory nutritional indicators, and adverse events during the WMT procedure.<br><br>RESULTS: 29 patients undergoing 74 WMTs were included for analysis. In total, 48.3% (14/29) of patients achieved clinical response post-WMT. Gastrointestinal symptoms, including diarrhea, mucous stool, abdominal pain, abdominal distention, and hematochezia, were significantly relieved post-WMT (all P < 0.05). Serum albumin and prealbumin levels were increased significantly post-WMT (P = 0.028 and 0.028, respectively). Eight self-limiting and transient adverse events, including diarrhea, abdominal pain, and abdominal distension, occurred after WMT.<br><br>CONCLUSION: This study indicated that WMT might be effective and safe for improving nutritional status and gastrointestinal symptoms in gastrointestinal disease-related malnourished children at 3-mo follow-up. WMT was expected to be a new therapeutic option for these patients.}, }
@article {pmid39861773, year = {2025}, author = {Ortiz-Islas, E and Montes, P and Rodríguez-Pérez, CE and Ruiz-Sánchez, E and Sánchez-Barbosa, T and Pichardo-Rojas, D and Zavala-Tecuapetla, C and Carvajal-Aguilera, K and Campos-Peña, V}, title = {Evolution of Alzheimer's Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy.}, journal = {Pharmaceutics}, volume = {17}, number = {1}, pages = {}, pmid = {39861773}, issn = {1999-4923}, support = {CF-2023-G-971 and CBF-2023-2024-1982//Ciencia de Frontera/ ; }, abstract = {Alzheimer's disease (AD) represents an escalating global health crisis, constituting the leading cause of dementia among the elderly and profoundly impairing their quality of life. Current FDA-approved drugs, such as rivastigmine, donepezil, galantamine, and memantine, offer only modest symptomatic relief and are frequently associated with significant adverse effects. Faced with this challenge and in line with advances in the understanding of the pathophysiology of this neurodegenerative condition, various innovative therapeutic strategies have been explored. Here, we review novel approaches inspired by advanced knowledge of the underlying pathophysiological mechanisms of the disease. Among the therapeutic alternatives, immunotherapy stands out, employing monoclonal antibodies to specifically target and eliminate toxic proteins implicated in AD. Additionally, the use of medicinal plants is examined, as their synergistic effects among components may confer neuroprotective properties. The modulation of the gut microbiota is also addressed as a peripheral strategy that could influence neuroinflammatory and degenerative processes in the brain. Furthermore, the therapeutic potential of emerging approaches, such as the use of microRNAs to regulate key cellular processes and nanotherapy, which enables precise drug delivery to the central nervous system, is analyzed. Despite promising advances in these strategies, the incidence of Alzheimer's disease continues to rise. Therefore, it is proposed that achieving effective treatment in the future may require the integration of combined approaches, maximizing the synergistic effects of different therapeutic interventions.}, }
@article {pmid39859091, year = {2025}, author = {Almonajjed, MB and Wardeh, M and Atlagh, A and Ismaiel, A and Popa, SL and Rusu, F and Dumitrascu, DL}, title = {Impact of Microbiota on Irritable Bowel Syndrome Pathogenesis and Management: A Narrative Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {1}, pages = {}, pmid = {39859091}, issn = {1648-9144}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/microbiology/physiopathology/etiology ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation/methods ; Quality of Life/psychology ; Dysbiosis/complications ; }, abstract = {Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, affecting 3-5% of the global population and significantly impacting patients' quality of life and healthcare resources. Alongside physical symptoms such as abdominal pain and altered bowel habits, many individuals experience psychological comorbidities, including anxiety and depression. Recent research has highlighted the critical role of the gut microbiota in IBS, with dysbiosis, characterized by an imbalance in microbial diversity, frequently observed in patients. The gut-brain axis, a bidirectional communication network between the gut and central nervous system, plays a central role in the development of IBS symptoms. Although interventions such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) have demonstrated potential in modulating the gut microbiota and alleviating symptoms, their efficacy remains an area of ongoing investigation. This review examines the interactions between the gut microbiota, immune system, and brain, emphasizing the need for personalized therapeutic strategies. Future research should aim to identify reliable microbiota-based biomarkers for IBS and refine microbiome-targeted therapies to enhance patient outcomes.}, }
@article {pmid39858858, year = {2025}, author = {Onisiforou, A and Charalambous, EG and Zanos, P}, title = {Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer's Disease Pathogenesis-From Gut Microbiota and Viruses to Brain Biofilms.}, journal = {Microorganisms}, volume = {13}, number = {1}, pages = {}, pmid = {39858858}, issn = {2076-2607}, support = {#101031962//European Commission Marie Sk&#x142;odowska-Curie fellowship/ ; EXCELLENCE/0421/0543//Research &amp; Innovation Foundation of Cyprus - Excellence Hubs 2021/ ; NA//IDSA Foundation/ ; }, abstract = {For decades, Alzheimer's Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as the primary driver of the disease. However, the consistent failure of Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores the need to rethink our approach to AD treatment. Emerging evidence points to microbial infections as environmental factors in AD pathoetiology. Although a definitive causal link remains unestablished, the collective evidence is compelling. This review explores unconventional perspectives and emerging paradigms regarding microbial involvement in AD pathogenesis, emphasizing the gut-brain axis, brain biofilms, the oral microbiome, and viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes brain Aβ accumulation, emphasizing gut-brain signaling pathways. Viral infections like Herpes Simplex Virus Type 1 (HSV-1) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead to AD by modulating host processes like the immune system. Aβ peptide's antimicrobial function as a response to microbial infection might inadvertently promote AD. We discuss potential microbiome-based therapies as promising strategies for managing and potentially preventing AD progression. Fecal microbiota transplantation (FMT) restores gut microbial balance, reduces Aβ accumulation, and improves cognition in preclinical models. Probiotics and prebiotics reduce neuroinflammation and Aβ plaques, while antiviral therapies targeting HSV-1 and vaccines like the shingles vaccine show potential to mitigate AD pathology. Developing effective treatments requires standardized methods to identify and measure microbial infections in AD patients, enabling personalized therapies that address individual microbial contributions to AD pathogenesis. Further research is needed to clarify the interactions between microbes and Aβ, explore bacterial and viral interplay, and understand their broader effects on host processes to translate these insights into clinical interventions.}, }
@article {pmid39858421, year = {2024}, author = {Gabrielli, M and Zileri Dal Verme, L and Zocco, MA and Nista, EC and Ojetti, V and Gasbarrini, A}, title = {The Role of the Gastrointestinal Microbiota in Parkinson's Disease.}, journal = {Biomolecules}, volume = {15}, number = {1}, pages = {}, pmid = {39858421}, issn = {2218-273X}, mesh = {*Parkinson Disease/microbiology/therapy ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Dysbiosis/microbiology/complications ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Helicobacter Infections/microbiology/complications ; Helicobacter pylori/pathogenicity ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {BACKGROUND/OBJECTIVES: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons leading to debilitating motor and non-motor symptoms. Beyond its well-known neurological features, emerging evidence underscores the pivotal role of the gut-brain axis and gastrointestinal microbiota in PD pathogenesis. Dysbiosis has been strongly linked to PD and is associated with increased intestinal permeability, chronic inflammation, and the production of neurotoxic metabolites that may exacerbate neuronal damage.<br><br>METHODS: This review delves into the complex interplay between PD and dysbiosis, shedding light on two peculiar subsets of dysbiosis, Helicobacter pylori infection and small-intestinal bacterial overgrowth. These conditions may not only contribute to PD progression but also influence therapeutic responses such as L-dopa efficacy.<br><br>CONCLUSIONS: The potential to modulate gut microbiota through probiotics, prebiotics, and synbiotics; fecal microbiota transplantation; and antibiotics represents a promising frontier for innovative PD treatments. Despite this potential, the current evidence is limited by small sample sizes and methodological variability across studies. Rigorous, large-scale, randomized placebo-controlled trials with standardized treatments in terms of composition, dosage, and duration are urgently needed to validate these findings and pave the way for microbiota-based therapeutic strategies in PD management.}, }
@article {pmid39858303, year = {2024}, author = {Morado, F and Nanda, N}, title = {A Review of Therapies for Clostridioides difficile Infection.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39858303}, issn = {2079-6382}, abstract = {Clostridioides difficile is an urgent public health threat that affects approximately half a million patients annually in the United States. Despite concerted efforts aimed at the prevention of Clostridioides difficile infection (CDI), it remains a leading cause of healthcare-associated infections. CDI is associated with significant clinical, social, and economic burdens. Therefore, it is imperative to provide optimal and timely therapy for CDI. We conducted a systematic literature review and offer treatment recommendations based on available evidence for the treatment and prevention of CDI.}, }
@article {pmid39857680, year = {2025}, author = {Radoš, L and Golčić, M and Mikolašević, I}, title = {The Relationship Between the Modulation of Intestinal Microbiota and the Response to Immunotherapy in Patients with Cancer.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857680}, issn = {2227-9059}, abstract = {The intestinal microbiota is an important part of the human body, and its composition can affect the effectiveness of immunotherapy. In the last few years, the modulation of intestinal microbiota in order to improve the effectiveness of immunotherapy has become a current topic in the scientific community, but there is a lack of research in this area. In this review, the goal was to analyze the current relevant literature related to the modulation of intestinal microbiota and the effectiveness of immunotherapy in the treatment of cancer. The effects of antibiotics, probiotics, diet, and fecal microbial transplantation were analyzed separately. It was concluded that the use of antibiotics, especially broad-spectrum types or larger quantities, causes dysbiosis of the intestinal microbiota, which can reduce the effectiveness of immunotherapy. While dysbiosis could be repaired by probiotics and thus improve the effectiveness of immunotherapy, the use of commercial probiotics without evidence of intestinal dysbiosis has not yet been sufficiently tested to confirm its safety for cancer for immunotherapy-treated cancer patients. A diet consisting of sufficient amounts of fiber, as well as a diet with higher salt content positively correlates with the success of immunotherapy. Fecal transplantation is a safe and realistic adjuvant option for the treatment of cancer patients with immunotherapy, but more clinical trials are necessary. Modulating the microbiota composition indeed changes the effectiveness of immunotherapy, but in the future, more human studies should be organized to precisely determine the types and procedures of microbiota modulation.}, }
@article {pmid39857657, year = {2024}, author = {Li, W and Gao, W and Yan, S and Yang, L and Zhu, Q and Chu, H}, title = {Gut Microbiota as Emerging Players in the Development of Alcohol-Related Liver Disease.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857657}, issn = {2227-9059}, support = {National Nature Science Foundation of China (No.81974078, No.81570530, and No.81370550)//Ling Yang/ ; National Key R&amp;D Program of China (No.2022YFA1305600)//Huikuan Chu/ ; Ministry of Science and Technology of China (No.2023YFC2413804)//Ling Yang/ ; Natural Science Foundation of Hubei Province (No.2019ACA1333)//Ling Yang/ ; }, abstract = {The global incidence and mortality rates of alcohol-related liver disease are on the rise, reflecting a growing health concern worldwide. Alcohol-related liver disease develops due to a complex interplay of multiple reasons, including oxidative stress generated during the metabolism of ethanol, immune response activated by immunogenic substances, and subsequent inflammatory processes. Recent research highlights the gut microbiota's significant role in the progression of alcohol-related liver disease. In patients with alcohol-related liver disease, the relative abundance of pathogenic bacteria, including Enterococcus faecalis, increases and is positively correlated with the level of severity exhibited by alcohol-related liver disease. Supplement probiotics like Lactobacillus, as well as Bifidobacterium, have been found to alleviate alcohol-related liver disease. The gut microbiota is speculated to trigger specific signaling pathways, influence metabolite profiles, and modulate immune responses in the gut and liver. This research aimed to investigate the role of gut microorganisms in the onset and advancement of alcohol-related liver disease, as well as to uncover the underlying mechanisms by which the gut microbiota may contribute to its development. This review outlines current treatments for reversing gut dysbiosis, including probiotics, fecal microbiota transplantation, and targeted phage therapy. Particularly, targeted therapy will be a vital aspect of future alcohol-related liver disease treatment. It is to be hoped that this article will prove beneficial for the treatment of alcohol-related liver disease.}, }
@article {pmid39855927, year = {2025}, author = {Wang, X and Zhao, D and Bi, D and Li, L and Tian, H and Yin, F and Zuo, T and Ianiro, G and Li, N and Chen, Q and Qin, H}, title = {Fecal microbiota transplantation: transitioning from chaos and controversial realm to scientific precision era.}, journal = {Science bulletin}, volume = {70}, number = {6}, pages = {970-985}, doi = {10.1016/j.scib.2025.01.029}, pmid = {39855927}, issn = {2095-9281}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; Precision Medicine ; }, abstract = {With the popularization of modern lifestyles, the spectrum of intestinal diseases has become increasingly diverse, presenting significant challenges in its management. Traditional pharmaceutical interventions have struggled to keep pace with these changes, leaving many patients refractory to conventional pharmaceutical treatments. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for enterogenic diseases. Still, controversies persist regarding its active constituents, mechanism of action, scheme of treatment evaluation, indications, and contraindications. In this review, we investigated the efficacy of FMT in addressing gastrointestinal and extraintestinal conditions, drawing from follow-up data on over 8000 patients. We systematically addressed the controversies surrounding FMT's clinical application. We delved into key issues such as its technical nature, evaluation methods, microbial restoration mechanisms, and impact on the host-microbiota interactions. Additionally, we explored the potential colonization patterns of FMT-engrafted new microbiota throughout the entire intestine and elucidated the specific pathways through which the new microbiota modulates host immunity, metabolism, and genome.}, }
@article {pmid39855612, year = {2025}, author = {Sutanto, H and Elisa, E and Rachma, B and Fetarayani, D}, title = {Gut Microbiome Modulation in Allergy Treatment: The Role of Fecal Microbiota Transplantation.}, journal = {The American journal of medicine}, volume = {138}, number = {5}, pages = {769-777.e3}, doi = {10.1016/j.amjmed.2025.01.005}, pmid = {39855612}, issn = {1555-7162}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; *Hypersensitivity/therapy/microbiology/immunology ; Dysbiosis/therapy/immunology ; }, abstract = {The prevalence of allergic diseases has been rising, paralleling lifestyle changes and environmental exposures that have altered human microbiome composition. This review article examines the intricate relationship between the gut microbiome and allergic diseases, emphasizing the potential of fecal microbiota transplantation as a promising novel treatment approach. It explains how reduced microbial exposure in modern societies contributes to immune dysregulation and the increasing incidence of allergies. The discussion also addresses immune homeostasis and its modulation by the gut microbiome, highlighting the shift from eubiosis to dysbiosis in allergic conditions. Furthermore, this article reviews existing studies and emerging research on the role of fecal microbiota transplantation in restoring microbial balance, providing insights into its mechanisms, efficacy, and safety.}, }
@article {pmid39854760, year = {2025}, author = {Chen, S and Zhang, D and Li, D and Zeng, F and Chen, C and Bai, F}, title = {Microbiome characterization of patients with Crohn disease and the use of fecal microbiota transplantation: A review.}, journal = {Medicine}, volume = {104}, number = {4}, pages = {e41262}, pmid = {39854760}, issn = {1536-5964}, support = {2021818//Hainan Province Clinical Medical Center/ ; YSPTZX202313//The specific research fund of The Innovation Platform for Academicians of Hainan Province/ ; 22A200078//Hainan Provincial Health Industry Research Project/ ; Qhyb2022-133//Hainan Provincial Postgraduate Innovation Research Project/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Crohn Disease/therapy/microbiology ; *Gastrointestinal Microbiome ; }, abstract = {Inflammatory bowel disease is a chronic inflammatory condition predominantly affecting the intestines, encompassing both ulcerative colitis and Crohn disease (CD). As one of the most common gastrointestinal disorders, CD's pathogenesis is closely linked with the intestinal microbiota. Recently, fecal microbiota transplantation (FMT) has gained attention as a potential treatment for CD, with the effective reestablishment of intestinal microecology considered a crucial mechanism of FMT therapy. This article synthesizes the findings of population-based cohort studies to enhance our understanding of gut microbial characteristics in patients with CD. It delves into the roles of "beneficial" and "pathogenic" bacteria in CD's development. This article systematically reviews and compares data on clinical response rates, remission rates, adverse events, and shifts in bacterial microbiota. Among these studies, gut microbiome analysis was conducted in only 7, and a single study examined the metabolome. Overall, FMT has demonstrated a partial restoration of typical CD-associated microbiological alterations, leading to increased α-diversity in responders and a moderate shift in patient microbiota toward the donor profile. Several factors, including donor selection, delivery route, microbial state (fresh or frozen), and recipient condition, are identified as pivotal in influencing FMT's effectiveness. Future prospective clinical studies with larger patient cohorts and improved methodologies are imperative. In addition, standardization of FMT procedures, coupled with advanced genomic techniques such as macroproteomics and culture genomics, is necessary. These advancements will further clarify the bacterial microbiota alterations that significantly contribute to FMT's therapeutic effects in CD treatment, as well as elucidate the underlying mechanisms of action.}, }
@article {pmid39854205, year = {2025}, author = {Yang, CJ and Peng, YS and Sung, PC and Hsieh, SY}, title = {Protocol for oral fecal gavage to reshape the gut microbiota in mice.}, journal = {STAR protocols}, volume = {6}, number = {1}, pages = {103585}, pmid = {39854205}, issn = {2666-1667}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Fecal Microbiota Transplantation/methods ; *Feces/microbiology ; Administration, Oral ; Mice, Inbred C57BL ; }, abstract = {Fecal microbiota transplantation (FMT) is clinically applied, while oral FMT (oral fecal gavage [OFG]) is preferred for experimental mice. Here, we present a protocol for OFG in antibiotic-pretreated mice, demonstrating the progressive, time-dependent evolution of the gut microbiota in the recipients. We describe steps for fecal sample collection and preparation procedures, oral gavage, and monitoring gut microbiota changes. This protocol serves as a general guide for reshaping the gut microbiota in recipient mice for various experimental applications. For complete details on the use and execution of this protocol, please refer to Yang et al.[1].}, }
@article {pmid39854158, year = {2025}, author = {Lau, RI and Su, Q and Ng, SC}, title = {Long COVID and gut microbiome: insights into pathogenesis and therapeutics.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2457495}, pmid = {39854158}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19/complications/microbiology/therapy ; Fecal Microbiota Transplantation ; *Dysbiosis/therapy/microbiology ; Probiotics/therapeutic use ; SARS-CoV-2/physiology ; Post-Acute COVID-19 Syndrome ; Prebiotics/administration &amp; dosage ; }, abstract = {Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome. Recent clinical trials have indicated that gut microbiome modulation using probiotics, prebiotics, and fecal microbiota transplantation (FMT) led to improvements in multiple symptoms related to PACS, including fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and disturbances in sleep and mood. In this review, we highlight the latest evidence on the key microbial alterations observed in PACS, as well as the use of microbiome-based therapeutics in managing PACS symptoms. These novel findings altogether shed light on the treatment of PACS and other chronic conditions.}, }
@article {pmid39851261, year = {2025}, author = {Zhao, X and Qiu, Y and Liang, L and Fu, X}, title = {Interkingdom signaling between gastrointestinal hormones and the gut microbiome.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2456592}, pmid = {39851261}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Animals ; *Gastrointestinal Hormones/metabolism ; Dysbiosis/microbiology/metabolism ; Bacteria/metabolism/classification/genetics ; Fecal Microbiota Transplantation ; Signal Transduction ; Inflammatory Bowel Diseases/microbiology/metabolism/therapy ; Gastrointestinal Tract/microbiology/metabolism ; }, abstract = {The interplay between the gut microbiota and gastrointestinal hormones plays a pivotal role in the health of the host and the development of diseases. As a vital component of the intestinal microecosystem, the gut microbiota influences the synthesis and release of many gastrointestinal hormones through mechanisms such as modulating the intestinal environment, producing metabolites, impacting mucosal barriers, generating immune and inflammatory responses, and releasing neurotransmitters. Conversely, gastrointestinal hormones exert feedback regulation on the gut microbiota by modulating the intestinal environment, nutrient absorption and utilization, and the bacterial biological behavior and composition. The distributions of the gut microbiota and gastrointestinal hormones are anatomically intertwined, and close interactions between the gut microbiota and gastrointestinal hormones are crucial for maintaining gastrointestinal homeostasis. Interventions leveraging the interplay between the gut microbiota and gastrointestinal hormones have been employed in the clinical management of metabolic diseases and inflammatory bowel diseases, such as bariatric surgery and fecal microbiota transplantation, offering promising targets for the treatment of dysbiosis-related diseases.}, }
@article {pmid39851236, year = {2025}, author = {Golob, JL and Hou, G and Swanson, BJ and Berinstein, JA and Bishu, S and Grasberger, H and Zataari, ME and Lee, A and Kao, JY and Kamada, N and Bishu, S}, title = {Inflammation-Induced Th17 Cells Synergize with the Inflammation-Trained Microbiota to Mediate Host Resiliency Against Intestinal Injury.}, journal = {Inflammatory bowel diseases}, volume = {31}, number = {4}, pages = {1082-1094}, doi = {10.1093/ibd/izae293}, pmid = {39851236}, issn = {1536-4844}, support = {K08DK123403//the NIDDK/ ; }, mesh = {Animals ; *Th17 Cells/immunology ; Mice ; Mice, Inbred C57BL ; Citrobacter rodentium ; *Colitis/immunology/chemically induced/microbiology/pathology ; *Inflammation/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Dextran Sulfate/toxicity ; *Intestinal Mucosa/immunology/pathology/microbiology ; Disease Models, Animal ; Mice, Knockout ; Fecal Microbiota Transplantation ; *Enterobacteriaceae Infections/immunology ; *Dysbiosis/immunology/microbiology ; }, abstract = {BACKGROUND AND AIMS: Inflammation can generate pathogenic Th17 cells and cause an inflammatory dysbiosis. In the context of inflammatory bowel disease (IBD), these inflammatory Th17 cells and dysbiotic microbiota may perpetuate injury to intestinal epithelial cells. However, many models of IBD like T-cell transfer colitis and IL-10-/- mice rely on the absence of regulatory pathways, so it is difficult to tell if inflammation can also induce protective Th17 cells.<br><br>METHODS: We subjected C57BL6, RAG1-/-, or JH-/- mice to systemic or gastrointestinal (GI) Citrobacter rodentium (Cr). Mice were then subjected to 2.5% dextran sodium sulfate (DSS) to cause epithelial injury. Fecal microbiota transfer was performed by bedding transfer and co-housing. Flow cytometry, qPCR, and histology were used to assess mucosal and systemic immune responses, cytokines, and tissue inflammation. 16s sequencing was used to assess gut bacterial taxonomy.<br><br>RESULTS: Transient inflammation with GI but not systemic Cr was protective against subsequent intestinal injury. This was replicated with sequential DSS collectively indicating that transient inflammation provides tissue-specific protection. Inflammatory Th17 cells that have a tissue-resident memory (TRM) signature expanded in the intestine. Experiments with reconstituted RAG1-/-, JH-/- mice, and cell trafficking inhibitors showed that inflammation-induced Th17 cells were required for protection. Fecal microbiota transfer showed that the inflammation-trained microbiota was necessary for protection, likely by maintaining protective Th17 cells in situ.<br><br>CONCLUSION: Inflammation can generate protective Th17 cells that synergize with the inflammation-trained microbiota to provide host resiliency against subsequent injury, indicating that inflammation-induced Th17 TRM T cells are heterogenous and contain protective subsets.}, }
@article {pmid39850178, year = {2024}, author = {Gandhi, DN and Pande, DN and Harikrishna, A and Advilkar, A and Basavan, I and Ansari, R}, title = {Beyond the Brain: Attention Deficit/Hyperactivity Disorder and the Gut-Brain Axis.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e76291}, pmid = {39850178}, issn = {2168-8184}, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental condition, predominantly affecting children, characterized by inattention, hyperactivity, and impulsivity. A growing body of evidence has highlighted the potential influence of the gut microbiota on the onset and presentation of ADHD symptoms. The gut microbiota, a diverse microbial ecosystem residing within the gastrointestinal tract, exerts multiple effects on systemic physiology, including immune modulation, metabolic regulation, and neuronal signalling. The bidirectional gut-brain axis serves as a conduit for communication between gut microbes and the central nervous system, implicating its disruption in neurodevelopmental disorders such as ADHD. This comprehensive literature review aims to shed light on how alterations in the gut microbiota influence the development and manifestation of ADHD symptoms. Examining potential mechanisms involving gut microbial metabolites and their impact on neurotransmitter modulation, neuro-endocrine signalling and neuroinflammation, we dissect the intricate interplay shaping ADHD pathology. Insights into these complex interactions hold promise for personalized therapeutic interventions aimed at modulating the gut microbiota to ameliorate ADHD symptoms. Discussions encompass dietary interventions, faecal microbiota-targeted therapies, and emerging probiotic approaches, underscoring their potential as adjunctive or alternative strategies in managing ADHD. Further research elucidating the precise mechanisms driving these interactions may pave the way for targeted and personalized interventions for individuals grappling with ADHD.}, }
@article {pmid39848238, year = {2025}, author = {Szajewska, H}, title = {An Overview of Early-Life Gut Microbiota Modulation Strategies.}, journal = {Annals of nutrition &amp; metabolism}, volume = {}, number = {}, pages = {1-6}, doi = {10.1159/000541492}, pmid = {39848238}, issn = {1421-9697}, abstract = {BACKGROUND: The gut microbiota, or microbiome, is essential for human health. Early-life factors such as delivery mode, diet, and antibiotic use shape its composition, impacting both short- and long-term health outcomes. Dysbiosis, or alterations in the gut microbiota, is linked to conditions such as allergies, asthma, obesity, diabetes, inflammatory bowel disease, and necrotizing enterocolitis in preterm infants.<br><br>SUMMARY: This article reviews current strategies to influence the early-life gut microbiome and their potential health impacts. It also briefly summarizes guidelines on using biotics for gastrointestinal and allergic diseases in children. Key strategies include vaginal or fecal microbiota transplantation for cesarean-born infants, breastfeeding, and biotic-supplemented formulas. While vaginal microbial transfer and maternal fecal microbiota transplantation show short-term benefits, further research is needed to determine long-term safety and efficacy. Breast milk, rich in human milk oligosaccharides, promotes a healthy microbiota and offers protection against infections. Biotic-supplemented formulas can improve the gut microbiota in formula-fed infants and show clinical effects, though each biotic must be evaluated separately. Probiotics given as dietary supplements outside of infant formulas show promise for treating gastrointestinal disorders but require further investigation.}, }
@article {pmid39845805, year = {2024}, author = {Shen, Y and Gao, Y and Yang, G and Zhao, Z and Zhao, Y and Gao, L and Li, S}, title = {Anti-colorectal cancer effect of total minor ginsenosides produced by lactobacilli transformation of major ginsenosides by inducing apoptosis and regulating gut microbiota.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1496346}, pmid = {39845805}, issn = {1663-9812}, abstract = {OBJECTIVE: Minor ginsenosides have demonstrated promising anticancer effects in previous reports. Total minor ginsenosides (TMG) were obtained through the fermentation of major ginsenosides with Lactiplantibacillus plantarum, and potential anticancer effects of TMGs on the mouse colon cancer cell line CT26.WT, in vitro and in vivo, were investigated.<br><br>MATERIALS AND METHODS: We employed the Cell Counting Kit-8 (CCK-8), TdT-mediated dUTP nick end labeling (TUNEL), and Western blot analysis in vitro to explore the anti-proliferative and pro-apoptotic functions of TMG in CT26.WT cells. In vivo, a xenograft model was established by subcutaneously injecting mice with CT26.WT cells and administering a dose of 100&#xa0;mg/kg/day TMG to the tumor-bearing mice. The level of apoptosis and expression of various proteins in the tumor tissues were detected by immunohistochemistry and Western blot. High-throughput 16S rRNA sequencing was used to determine the alterations in the gut microbiota.<br><br>RESULTS: In vitro studies demonstrated that TMG significantly inhibited proliferation and promoted apoptosis in CT26.WT cells. Interestingly, TMG induced apoptosis in CT26.WT cells by affecting the Bax/Bcl-2/caspase-3 pathway. Furthermore, the result of the transplanted tumor model indicated that TMG substantially enhanced the activities of Bax and caspase-3, reduced the activity of Bcl-2, and suppressed the expression of Raf/MEK/ERK protein levels. Fecal analysis revealed that TMG reconstructed the gut microbiota in colorectal cancer-affected mice by augmenting the abundance of the advantageous bacterium Lactobacillus and decreasing the abundance of the harmful bacterium Proteus.<br><br>CONCLUSION: TMG can exhibit potent anti-colorectal cancer effects through diverse apoptotic mechanisms, with their mode of action closely related to the regulation of gut microbiota.}, }
@article {pmid39845049, year = {2024}, author = {Wu, R and Mai, Z and Song, X and Zhao, W}, title = {Hotspots and research trends of gut microbiome in polycystic ovary syndrome: a bibliometric analysis (2012-2023).}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1524521}, pmid = {39845049}, issn = {1664-302X}, abstract = {INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common gynecological condition affecting individuals of reproductive age and is linked to the gut microbiome. This study aimed to identify the hotspots and research trends within the domain of the gut microbiome in PCOS through bibliometric analysis.<br><br>METHODS: Utilizing bibliometric techniques, we examined the literature on the gut microbiome in PCOS from the Web of Science Core Collection spanning the period from 2012 to 2023. Analytical tools such as CiteSpace, VOSviewer, and Bibliometric R packages were employed to evaluate various metrics, including countries/regions, institutions, authors, co-cited authors, authors' H-index, journals, co-references, and keywords.<br><br>RESULTS: A total of 191 publications were identified in the field of gut microbiome in PCOS, with an increase in annual publications from 2018 to 2023. People's Republic of China was the most productive country, followed by the United States of America (USA), India. Shanghai Jiao Tong University, Fudan University, and Beijing University of Chinese Medicine were the top three most publications institutions. Thackray VG was identified as the most prolific author, holding the highest H-index, while Liu R received the highest total number of citations. The journal "Frontiers in Endocrinology" published the most articles in this domain. The most frequently co-cited reference was authored by Qi XY. The analysis of keyword burst detection identified "bile acids" (2021-2023) as the leading frontier keyword. Additionally, "gut dysbiosis," "phenotypes," "adolescents," "metabolomics," "metabolites," "fecal microbiota transplantation," and "IL-22" have emerged as the primary keywords reflecting recent research trends.<br><br>CONCLUSION: This bibliometric analysis explores how the gut microbiome influences endocrine and metabolic disorders related to PCOS, emphasizing its role in the development of PCOS and treatments targeting the gut microbiome. The findings serve as a valuable resource for researchers, enabling them to identify critical hotspots and emerging areas of investigation in this field.}, }
@article {pmid39844078, year = {2025}, author = {Fan, X and Li, J and Gao, Y and Li, L and Zhang, H and Bi, Z}, title = {The mechanism of enterogenous toxin methylmalonic acid aggravating calcium-phosphorus metabolic disorder in uremic rats by regulating the Wnt/β-catenin pathway.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {19}, pmid = {39844078}, issn = {1528-3658}, mesh = {Animals ; *Uremia/metabolism/etiology/pathology ; Rats ; *Wnt Signaling Pathway/drug effects ; *Calcium/metabolism ; *Phosphorus/metabolism ; Male ; *Methylmalonic Acid/toxicity/metabolism ; Disease Models, Animal ; Podocytes/metabolism/drug effects ; Gastrointestinal Microbiome ; Apoptosis/drug effects ; Rats, Sprague-Dawley ; beta Catenin/metabolism ; }, abstract = {BACKGROUND: Uremia (UR) is caused by increased UR-related toxins in the bloodstream. We explored the mechanism of enterogenous toxin methylmalonic acid (MMA) in calcium-phosphorus metabolic disorder in UR rats via the Wnt/β-catenin pathway.<br><br>METHODS: The UR rat model was established by 5/6 nephrectomy. The fecal bacteria of UR rats were transplanted into Sham rats. Sham rats were injected with exogenous MMA or Salinomycin (SAL). Pathological changes in renal/colon tissues were analyzed. MMA concentration, levels of renal function indicators, serum inflammatory factors, Ca[2+]/P[3+], and parathyroid hormone, intestinal flora structure, fecal metabolic profile, intestinal permeability, and glomerular filtration rate (GFR) were assessed. Additionally, rat glomerular podocytes were cultured, with cell viability and apoptosis measured.<br><br>RESULTS: Intestinal flora richness and diversity in UR rats were decreased, along with unbalanced flora structure. Among the screened 133 secondary differential metabolites, the MMA concentration rose, showing the most significant difference. UR rat fecal transplantation caused elevated MMA concentration in the serum and renal tissues of Sham rats. The intestinal flora metabolite MMA or exogenous MMA promoted intestinal barrier impairment, increased intestinal permeability, induced glomerular podocyte loss, and reduced GFR, causing calcium-phosphorus metabolic disorder. The intestinal flora metabolite MMA or exogenous MMA induced inflammatory responses and facilitated glomerular podocyte apoptosis by activating the Wnt/&#x3b2;-catenin pathway, which could be counteracted by repressing the Wnt/&#x3b2;-catenin pathway.<br><br>CONCLUSIONS: Enterogenous toxin MMA impelled intestinal barrier impairment in UR rats, enhanced intestinal permeability, and activated the Wnt/&#x3b2;-catenin pathway to induce glomerular podocyte loss and reduce GFR, thus aggravating calcium-phosphorus metabolic disorder.}, }
@article {pmid39843757, year = {2025}, author = {Pitashny, M and Kesten, I and Shlon, D and Hur, DB and Bar-Yoseph, H}, title = {The Future of Microbiome Therapeutics.}, journal = {Drugs}, volume = {85}, number = {2}, pages = {117-125}, pmid = {39843757}, issn = {1179-1950}, mesh = {Humans ; *Microbiota/drug effects ; Fecal Microbiota Transplantation/methods ; Phage Therapy/methods ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Synthetic Biology/methods ; Animals ; }, abstract = {The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy. Advancements in technology are paving the way for the development of novel microbiome therapeutics, across a wide range of indications. In this narrative review, we provide an overview of state-of-the-art technologies in late-stage development, examining their advantages and limitations. By covering a spectrum, from fecal-derived products to live biotherapeutics, phage therapy, and synthetic biology, we illuminate the path toward the future of microbiome therapeutics.}, }
@article {pmid39840995, year = {2025}, author = {Hua, D and Yang, Q and Li, X and Zhou, X and Kang, Y and Zhao, Y and Wu, D and Zhang, Z and Li, B and Wang, X and Qi, X and Chen, Z and Cui, G and Hong, W}, title = {The combination of Clostridium butyricum and Akkermansia muciniphila mitigates DSS-induced colitis and attenuates colitis-associated tumorigenesis by modulating gut microbiota and reducing CD8[+] T cells in mice.}, journal = {mSystems}, volume = {10}, number = {2}, pages = {e0156724}, pmid = {39840995}, issn = {2379-5077}, support = {32160015,32170134,32460046//MOST | National Natural Science Foundation of China (NSFC)/ ; (2022)101//Excellent Young Talents Plan of Guizhou Medical University/ ; (2022-08)//Innovation and Entrepreneurship project for overseas talents in Guizhou/ ; (QJJ [2022] 019)//Guizhou Provincical Key Laboratory of Pathogen Biology/ ; (D20009)//111 Program/ ; ([2020]4101)//International sciencesn and technology cooperation base of Guizhou/ ; (GCC[2022] 036-1)//Guizhou province high-level innovation talent team and talent baseproject/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Clostridium butyricum ; Mice ; *Probiotics/pharmacology/administration &amp; dosage ; *Colitis/chemically induced/microbiology/therapy/complications ; *CD8-Positive T-Lymphocytes/immunology ; Dextran Sulfate/toxicity ; Mice, Inbred C57BL ; Colorectal Neoplasms ; Disease Models, Animal ; Carcinogenesis/drug effects ; Male ; Akkermansia ; }, abstract = {UNLABELLED: The gut microbiota is closely associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC). Probiotics such as Clostridium butyricum (CB) or Akkermansia muciniphila (AKK) have the potential to treat inflammatory bowel disease (IBD) or colorectal cancer (CRC). However, research on the combined therapeutic effects and immunomodulatory mechanisms of CB and AKK in treating IBD or CRC has never been studied. This study evaluates the potential of co-administration of CB and AKK in treating DSS/AOM-induced IBD and colitis-associated CRC. Our results indicate that compared to mono-administration, the co-administration of CB and AKK not only significantly alleviates symptoms such as weight loss, colon shortening, and increased Disease Activity Index in IBD mice but also regulates the gut microbiota composition and effectively suppresses colonic inflammatory responses. In the colitis-associated CRC mice model, a combination of CB and AKK significantly alleviates weight loss and markedly reduces inflammatory infiltration of macrophages and cytotoxic T lymphocytes (CTLs) in the colon, thereby regulating anti-tumor immunity and inhibiting the occurrence of inflammation-induced CRC. In addition, we found that the combined probiotic therapy of CB and AKK can enhance the sensitivity of colitis-associated CRC mice to the immune checkpoint inhibitor anti-mouse PD-L1 (aPD-L1), significantly improving the anti-tumor efficacy of immunotherapy and the survival rate of colitis-associated CRC mice. Furthermore, fecal microbiota transplantation therapy showed that transplanting feces from CRC mice treated with the co-administration of CB and AKK into other CRC mice alleviated the tumor loads in the colon and significantly extended their survival rate. Our study suggests that the combined use of two probiotics, CB and AKK, can not only alleviate chronic intestinal inflammation but also inhibit the progression to CRC. This may be a natural and relatively safe method to support the gut microbiota and enhance the host's immunity against cancer.<br><br>IMPORTANCE: Our study suggests that the combined administration of CB and AKK probiotics, as opposed to a single probiotic strain, holds considerable promise in preventing the advancement of IBD to CRC. This synergistic effect is attributed to the ability of this probiotic combination to more effectively modulate the gut microbiota, curb inflammatory reactions, bolster the efficacy of immunotherapeutic approaches, and optimize treatment results via fecal microbiota transplantation.}, }
@article {pmid39840614, year = {2025}, author = {Liu, W and Wang, J and Yang, H and Li, C and Lan, W and Chen, T and Tang, Y}, title = {The Metabolite Indole-3-Acetic Acid of Bacteroides Ovatus Improves Atherosclerosis by Restoring the Polarisation Balance of M1/M2 Macrophages and Inhibiting Inflammation.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {11}, pages = {e2413010}, pmid = {39840614}, issn = {2198-3844}, support = {82360105//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 20232ACB206001//Natural Science Foundation of Jiangxi Province/ ; 20223BBG71010//Key Research and Development Program of Jiangxi Province/ ; 2024SSY07061//Jiangxi Province Key Laboratory of bioengineering drugs/ ; }, mesh = {*Atherosclerosis/metabolism/microbiology ; Humans ; *Indoleacetic Acids/metabolism/pharmacology ; *Macrophages/metabolism/drug effects ; *Gastrointestinal Microbiome/physiology/drug effects ; *Bacteroides/metabolism ; *Inflammation/metabolism ; Male ; Animals ; Female ; Mice ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Middle Aged ; }, abstract = {Emerging research has highlighted the significant role of the gut microbiota in atherosclerosis (AS), with microbiota-targeted interventions offering promising therapeutic potential. A central component of this process is gut-derived metabolites, which play a crucial role in mediating the distal functioning of the microbiota. In this study, a comprehensive microbiome-metabolite analysis using fecal and serum samples from patients with atherosclerotic cardiovascular disease and volunteers with risk factors for coronary heart disease and culture histology is performed, and identified the core strain Bacteroides ovatus (B. ovatus). Fecal microbiota transplantation experiments further demonstrated that the gut microbiota significantly influences AS progression, with B. ovatus alone exerting effects comparable to volunteer feces from volunteers. Notably, B. ovatus alleviated AS primarily by restoring the intestinal barrier and enhancing bile acid metabolism, particularly through the production of indole-3-acetic acid (IAA), a tryptophan-derived metabolite. IAA inhibited the TLR4/MyD88/NF-κB pathway in M1 macrophages, promoted M2 macrophage polarisation, and restored the M1/M2 polarisation balance, ultimately reducing aortic inflammation. These findings clarify the mechanistic interplay between the gut microbiota and AS, providing the first evidence that B. ovatus, a second-generation probiotic, can improve bile acid metabolism and reduce inflammation, offering a theoretical foundation for future AS therapeutic applications involving this strain.}, }
@article {pmid39840031, year = {2024}, author = {Lim, MY and Hong, S and Nam, YD}, title = {Understanding the role of the gut microbiome in solid tumor responses to immune checkpoint inhibitors for personalized therapeutic strategies: a review.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1512683}, pmid = {39840031}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Neoplasms/immunology/therapy/drug therapy/microbiology ; Precision Medicine/methods ; Immunotherapy/methods ; Animals ; Fecal Microbiota Transplantation ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Immunotherapy, especially immune checkpoint inhibitor (ICI) therapy, has yielded remarkable outcomes for some patients with solid cancers, but others do not respond to these treatments. Recent research has identified the gut microbiota as a key modulator of immune responses, suggesting that its composition is closely linked to responses to ICI therapy in cancer treatment. As a result, the gut microbiome is gaining attention as a potential biomarker for predicting individual responses to ICI therapy and as a target for enhancing treatment efficacy. In this review, we discuss key findings from human observational studies assessing the effect of antibiotic use prior to ICI therapy on outcomes and identifying specific gut bacteria associated with favorable and unfavorable responses. Moreover, we review studies investigating the possibility of patient outcome prediction using machine learning models based on gut microbiome data before starting ICI therapy and clinical trials exploring whether gut microbiota modulation, for example via fecal microbiota transplantation or live biotherapeutic products, can improve results of ICI therapy in patients with cancer. We also briefly discuss the mechanisms through which the gut microbial-derived products influence immunotherapy effectiveness. Further research is necessary to fully understand the complex interactions between the host, gut microbiota, and immunotherapy and to develop personalized strategies that optimize responses to ICI therapy.}, }
@article {pmid39839105, year = {2024}, author = {Correa Lopes, B and Turck, J and Tolbert, MK and Giaretta, PR and Suchodolski, JS and Pilla, R}, title = {Prolonged storage reduces viability of Peptacetobacter (Clostridium) hiranonis and core intestinal bacteria in fecal microbiota transplantation preparations for dogs.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1502452}, pmid = {39839105}, issn = {1664-302X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) has been described useful as an adjunct treatment for chronic enteropathy in dogs. Different protocols can be used to prepare and store FMT preparations, however, the effect of these methods on microbial viability is unknown. We aimed (1) to assess the viability of several core intestinal bacterial species by qPCR and (2) to assess Peptacetobacter (Clostridium) hiranonis viability through culture to further characterize bacterial viability in different protocols for FMT preparations.<br><br>METHODS: Bacterial abundances were assessed in feces from six healthy dogs by qPCR after propidium monoazide (PMA-qPCR) treatment for selective quantitation of viable bacteria. Conservation methods tested included lyophilization (stored at 4&#xb0;C and at -20&#xb0;C) and freezing with glycerol-saline solution (12.5%) and without any cryoprotectant (stored at -20&#xb0;C). Additionally, the abundance of P. hiranonis was quantified using bacterial culture.<br><br>RESULTS: Using PMA-qPCR, the viability of Faecalibacterium, Escherichia coli, Streptococcus, Blautia, Fusobacterium, and P. hiranonis was reduced in lyophilized fecal samples kept at 4&#xb0;C and -20&#xb0;C up to 6 months (p < 0.05). In frozen feces without cryoprotectant, only Streptococcus and E. coli were not significantly reduced for up to 3 months (p > 0.05). Lastly, no differences were observed in the viability of those species in glycerol-preserved samples up to 6 months (p > 0.05). When using culture to evaluate the viability of P. hiranonis, we observed that P. hiranonis abundance was lower in lyophilized samples kept at 4&#xb0;C than -20&#xb0;C; and P. hiranonis abundance was higher in glycerol-preserved samples for up to 6 months than in samples preserved without glycerol for up to 3 months. Moreover, the highest abundance of P. hiranonis was observed in glycerol-preserved feces. After 3 months, P. hiranonis was undetectable by culture in 83% (5/6) of the frozen samples without glycerol.<br><br>DISCUSSION: While the lyophilization procedure initially reduced P. hiranonis abundance, P. hiranonis viability was stable thereafter for up to 6 months at -20&#xb0;C. The higher bacterial viability detected in fecal samples preserved with glycerol confirms the use of this cryoprotectant as a reliable method to keep bacteria alive in the presence of fecal matrix for FMT purposes.}, }
@article {pmid39838262, year = {2025}, author = {Ye, J and Shi, R and Wu, X and Fan, H and Zhao, Y and Hu, X and Wang, L and Bo, X and Li, D and Ge, Y and Wang, D and Xia, B and Zhao, Z and Xiao, C and Zhao, B and Wang, Y and Liu, X}, title = {Stevioside mitigates metabolic dysregulation in offspring induced by maternal high-fat diet: the role of gut microbiota-driven thermogenesis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2452241}, doi = {10.1080/19490976.2025.2452241}, pmid = {39838262}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Female ; Diet, High-Fat/adverse effects ; Mice ; Pregnancy ; *Thermogenesis/drug effects ; *Diterpenes, Kaurane/pharmacology/administration &amp; dosage ; *Glucosides/administration &amp; dosage/pharmacology ; Mice, Inbred C57BL ; Male ; Lipid Metabolism/drug effects ; Obesity ; Lactobacillus/drug effects ; *Prenatal Exposure Delayed Effects ; Dietary Supplements ; }, abstract = {Maternal obesity poses a significant threat to the metabolic profiles of offspring. Microorganisms acquired from the mother early in life critically affect the host's metabolic functions. Natural non-nutritive sweeteners, particularly stevioside (STV), play a crucial role in reducing obesity and affecting gut microbiota composition. Based on this, we hypothesized that maternal STV supplementation could improve the health of mothers and offspring by altering their gut microbiota. Our study found that maternal STV supplementation reduced obesity during pregnancy, decreased abnormal lipid accumulation in offspring mice caused by maternal obesity, and modified the gut microbiota of both dams and offspring, notably increasing the abundance of Lactobacillus apodemi (L. apodemi). Co-housing and fecal microbiota transplant experiments confirmed that gut microbiota mediated the effects of STV on metabolic disorders. Furthermore, treatment with L. apodemi alone replicated the beneficial effects of STV, which were associated with increased thermogenesis. In summary, maternal STV supplementation could alleviate lipid metabolic disorders in offspring by enhancing L. apodemi levels and promoting thermogenic activity, potentially involving changes in bile acid metabolism pathways.}, }
@article {pmid39837364, year = {2025}, author = {Liu, H and Yang, S and Zhang, Q and Wang, S and Zhang, B and Xu, Y and Fu, X and Zhou, S and Zhang, P and Wang, H and Di, L and Xu, X and Xu, X and Liu, C and Yang, C and Wang, Y and Jiang, R}, title = {S-ketamine alleviates morphine-induced hyperalgesia via decreasing the gut Enterobacteriaceae levels: Comparison with R-ketamine.}, journal = {Neuroscience}, volume = {568}, number = {}, pages = {240-252}, doi = {10.1016/j.neuroscience.2025.01.022}, pmid = {39837364}, issn = {1873-7544}, mesh = {Animals ; *Morphine/toxicity ; *Ketamine/pharmacology/chemistry ; *Hyperalgesia/chemically induced/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Male ; Fecal Microbiota Transplantation ; *Enterobacteriaceae/drug effects ; Analgesics, Opioid ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; *Analgesics/pharmacology ; }, abstract = {BACKGROUND: Opioid-induced hyperalgesia (OIH) is a serious complication during the pain treatment. Ketamine has been commonly reported to treat OIH, but the mechanisms remain unclear. Gut microbiota is recently recognized as one of the important mechanisms underlying the occurrence and treatment of OIH. However, whether ketamine enantiomers could alleviate OIH through gut microbiota that still needs to be clarified.<br><br>METHODS: The OIH model was established by morphine injection for 3 consecutive days, followed by hierarchical clustering analysis of behavioral results into susceptible or resilient group. Broad-spectrum antibiotic cocktail (ABx) was used to eradicated the gut microbiota of mice. Subsequently, fecal microbiota transplantation (FMT) was performed. S- or R-ketamine was administered as pretreatment 30&#xa0;min before morphine injection. Fecal samples were collected for 16S rRNA gene sequencing after completion of all behavioral tests.<br><br>RESULTS: Approximately 60% of the mice developed OIH after morphine exposure with abnormal locomotion and anxiety-like behaviors. Pseudo germ-free mice treated with ABx did not develop hyperalgesia, whereas pseudo germ-free mice that received fecal microbiota transplantation from OIH mice developed hyperalgesia. Interestingly, S-ketamine but not R-ketamine rescued mice from OIH. The principal co-ordinates analysis (PCoA) suggested that the distribution of gut microbiota differed among the groups. Importantly, levels of Enterobacteriaceae were increased in OIH susceptible group, while decreased after S-ketamine treatment.<br><br>CONCLUSION: S-ketamine but not R-ketamine was able to alleviate morphine-induced OIH, and this mechanism is probably related to decreasing the levels of gut Enterobacteriaceae.}, }
@article {pmid39836853, year = {2024}, author = {Aristizábal, AM and Montaña, LP and Gutiérrez, J and Medina, D and Franco, AA and Manzi, E and Zapata, &#xc1;D and Mosquera, W}, title = {Intra-mesenteric steroids for steroid-refractory graft-versus-host disease in pediatric patients: A safe option.}, journal = {Biomedica : revista del Instituto Nacional de Salud}, volume = {44}, number = {Sp. 2}, pages = {63-71}, pmid = {39836853}, issn = {2590-7379}, mesh = {Humans ; *Graft vs Host Disease/drug therapy/etiology/mortality ; Child ; Male ; Female ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Child, Preschool ; Adolescent ; *Methylprednisolone/administration &amp; dosage/therapeutic use ; Retrospective Studies ; Drug Resistance ; Infant ; }, abstract = {INTRODUCTION: Graft-versus-host disease is a serious complication after hematopoietic stem cell transplantation and is a major cause of death post-transplantation. Approximately 50% of acute graft-versus-host disease patients do not respond to systemic steroids and their prognosis is poor regardless of the treatment. This study describes our experience with pediatric patients diagnosed with steroid-refractory graft-versus-host disease who received intra-mesenteric steroid treatment.<br><br>OBJECTIVE: To determine the outcomes of intra-mesenteric steroid use in the management of pediatric patients diagnosed with refractory graft-versus-host disease.<br><br>MATERIALS AND METHODS: The study included patients under 18 years old with allogeneic hematopoietic stem cell transplantation who underwent intra-mesenteric steroid injection for resistant gastrointestinal graft-versus-host disease between January, 2016, and December, 2021. Methylprednisolone was administered via intra-arterial injection through the celiac trunk and the superior and inferior mesenteric arteries.<br><br>RESULTS: We collected data on 21 patients: nine (90%) responded with a subjective decrease in fecal output and a reduction in bilirubin and transaminases. Seven patients required a second intra-mesenteric injection and presented a complete response in 85% of the cases. Only one patient experienced local complications after the procedure. Twelve patients (57%) died with one death due to acute graft-versus-host disease.<br><br>CONCLUSION: Reports in the adult population have shown an approximately 50% response rate with few complications, making it a second-line management standard. As far as we know, this is the largest pediatric cohort reported in Latin America. Our findings suggest that intra-mesenteric steroid administration for managing hepatic and gastrointestinal graftversus-host disease may be considered an early adjuvant treatment in patients with steroidrefractory graft-versus-host disease.}, }
@article {pmid39836604, year = {2025}, author = {Wu, X and Wei, J and Ran, W and Liu, D and Yi, Y and Gong, M and Liu, X and Gong, Q and Li, H and Gao, J}, title = {The Gut Microbiota-Xanthurenic Acid-Aromatic Hydrocarbon Receptor Axis Mediates the Anticolitic Effects of Trilobatin.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {10}, pages = {e2412234}, pmid = {39836604}, issn = {2198-3844}, support = {GCC[2023]042//Guizhou Province/ ; HZ(2024)302//Science and technology project of Zunyi/ ; ZYSE-2022-02//Zunyi Medical University/ ; [2021]1350-037//Talent project of Guizhou platform/ ; 2022(2022JH2/101300058)//Liaoning Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Receptors, Aryl Hydrocarbon/metabolism ; Mice ; *Xanthurenates/metabolism ; *Colitis, Ulcerative/drug therapy/metabolism/microbiology ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Dextran Sulfate ; }, abstract = {Current treatments for ulcerative colitis (UC) remain limited, highlighting the need for novel therapeutic strategies. Trilobatin (TLB), a naturally derived food additive, exhibits potential anti-inflammatory properties. In this study, a dextran sulfate sodium (DSS)-induced animal model is used to investigate the effects of TLB on UC. It is found TLB significantly alleviates DSS-induced UC in mice, as evidenced by a reduction in the disease activity index, an increase in colon length, improvement in histopathological lesions. Furthermore, TLB treatment results in a decrease in proinflammatory cytokines and an increase in anti-inflammatory cytokines. TLB mitigates UC by modulating the intestinal microbiota, particularly Akkermansia, which enhances tryptophan metabolism and upregulates the production of xanthurenic acid (XANA). To confirm the role of TLB-induced microbiota changes, experiments are performed with pseudogerm-free mice and fecal transplantation. It is also identified XANA as a key metabolite that mediates TLB's protective effects. Both TLB and XANA markedly activate the aromatic hydrocarbon receptor (AhR). Administration of an AhR antagonist abrogates their protective effects, thereby confirming the involvement of AhR in the underlying mechanism. In conclusion, the study reveals a novel mechanism through which TLB alleviates UC by correcting microbiota imbalances, regulating tryptophan metabolism, enhancing XANA production, and activating AhR.}, }
@article {pmid39834471, year = {2024}, author = {Song, Y and Liu, S and Zhang, L and Zhao, W and Qin, Y and Liu, M}, title = {The effect of gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review and network meta-analysis.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1470185}, pmid = {39834471}, issn = {2296-861X}, abstract = {BACKGROUND: The incidence of NAFLD is increasing. Preclinical evidences indicate that modulation of the gut microbiome could be a promising target in nonalcoholic fatty liver disease.<br><br>METHOD: A systematic review and network meta-analysis was conducted to compare the effect of probiotics, synbiotics, prebiotics, fecal microbiota transplant, and antibiotics on the liver-enzyme, metabolic effects and liver-specific in patients with NAFLD. The randomized controlled trails (RCTs), limited to English language were searched from database such as Pubmed, Embase, Web of science and Cochrane Library from inception to November 2024. Review Manager 5.3 was used to to draw a Cochrane bias risk. Inconsistency test and publication-bias were assessed by Stata 14.0. Random effect model was used to assemble direct and indirect evidences. The effects of the intervention were presented as mean differences with 95% confidence interval.<br><br>RESULTS: A total of 1921 patients from 37 RCTs were eventually included in our study. 23 RCTs evaluated probiotics, 10 RCTs evaluated synbiotics, 4 RCTs evaluated prebiotics, 3 RCTs evaluated FMT and one RCT evaluated antibiotics. Probiotics and synbiotics were associated with a significantly reduction in alanine aminotransferase [ALT, (MD: -5.09; 95%CI: -9.79, -0.39), (MD: -7.38, 95CI%: -11.94, -2.82)] and liver stiffness measurement by elastograph [LSM, (MD: -0.37;95%CI: -0.49, -0.25), (MD: -1.00;95%CI: -1.59, -0.41)]. In addition to, synbiotics was superior to probiotics in reducing LSM. Synbiotics was associated with a significant reduction of Controlled Attenuation Parameter [CAP, (MD: -39.34; 95%CI: -74.73, -3.95)]. Both probiotics and synbiotics were associated with a significant reduction of aspartate transaminase [AST, (MD: -7.81; 95%CI: -15.49, -0.12), (MD: -13.32; 95%CI: -23, -3.64)]. Probiotics and Allogenic FMT was associated with a significant reduction of Homeostatic Model Assessment for Insulin Resistance [HOMA-IR, (MD: -0.7, 95%CI: -1.26, -0.15), (MD: -1.8, 95%CI: -3.53, - 0.07)]. Probiotics was associated with a significant reduction of body mass index [BMI, MD: -1.84, 95%CI: -3.35, -0.33].<br><br>CONCLUSION: The supplement of synbiotics and probiotics maybe a promising way to improve liver-enzyme, LSM, and steatosis in patients with NAFLD. More randomized controlled trials are needed to determine the efficacy of FMT and antibiotics on NAFLD. And the incidence of adverse events of MTTs should be further explored.<br><br>https://www.crd.york.ac.uk/prospero/, CRD42023450093.}, }
@article {pmid39829898, year = {2025}, author = {Ni, M and Fan, Y and Liu, Y and Li, Y and Qiao, W and Davey, LE and Zhang, XS and Ksiezarek, M and Mead, EA and Tourancheau, A and Jiang, W and Blaser, MJ and Valdivia, RH and Fang, G}, title = {Epigenetic phase variation in the gut microbiome enhances bacterial adaptation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39829898}, issn = {2692-8205}, support = {R35 GM139655/GM/NIGMS NIH HHS/United States ; }, abstract = {The human gut microbiome within the gastrointestinal tract continuously adapts to variations in diet, medications, and host physiology. A strategy for bacterial genetic adaptation is epigenetic phase variation (ePV) mediated by bacterial DNA methylation, which can regulate gene expression, enhance clonal heterogeneity, and enable a single bacterial strain to exhibit variable phenotypic states. Genome-wide and site-specific ePVs have been characterized in human pathogens' antigenic variation and virulence factor production. However, the role of ePV in facilitating adaptation within the human microbiome remains poorly understood. Here, we comprehensively cataloged genome-wide and site-specific ePV in human infant and adult gut microbiomes. First, using long-read metagenomic sequencing, we detected genome-wide ePV mediated by complex structural variations of DNA methyltransferases, highlighting those associated with antibiotics or fecal microbiota transplantation. Second, we analyzed a collection of public short-read metagenomic sequencing datasets, uncovering a great prevalence of genome-wide ePV in the human gut microbiome. Third, we quantitatively detected site-specific ePVs using single-molecule methylation analysis to identify dynamic variation associated with antibiotic treatment or probiotic engraftment. Finally, we performed an in-depth assessment of an Akkermansia muciniphila isolate from an infant, highlighting that ePVs can regulate gene expression and enhance the bacterial adaptive capacity by employing a bet-hedging strategy to increase tolerance to differing antibiotics. Our findings indicate that epigenetic modifications are a common strategy used by gut bacteria to adapt to the fluctuating environment.}, }
@article {pmid39829204, year = {2025}, author = {Liu, C and Wong, PY and Barua, N and Li, B and Wong, HY and Zhang, N and Chow, SKH and Wong, SH and Yu, J and Ip, M and Cheung, WH and Duque, G and Brochhausen, C and Sung, JJY and Wong, RMY}, title = {From Clinical to Benchside: Lacticaseibacillus and Faecalibacterium Are Positively Associated With Muscle Health and Alleviate Age-Related Muscle Disorder.}, journal = {Aging cell}, volume = {}, number = {}, pages = {e14485}, doi = {10.1111/acel.14485}, pmid = {39829204}, issn = {1474-9726}, support = {C4032-21GF//Collaborative Research Fund, HKSAR Research Grants Council/ ; 14116223//General Research Fund, HKSAR Research Grants Council/ ; }, abstract = {Sarcopenia is an age-related muscle disorder that increases risks of adverse clinical outcomes, but its treatments are still limited. Gut microbiota is potentially associated with sarcopenia, and its role is still unclear. To investigate the role of gut microbiota in sarcopenia, we first compared gut microbiota and metabolites composition in old participants with or without sarcopenia. Fecal microbiota transplantation (FMT) from human donors to antibiotic-treated recipient mice was then performed. Specific probiotics and their mechanisms to treat aged mice were identified. Old people with sarcopenia had different microbial composition and metabolites, including Paraprevotella, Lachnospira, short-chain fatty acids, and purine. After FMT, mice receiving microbes from people with sarcopenia displayed lower muscle mass and strength compared with those receiving microbes from non-sarcopenic donors. Lacticaseibacillus rhamnosus (LR) and Faecalibacterium prausnitzii (FP) were positively related to muscle health of old people, and enhanced muscle mass and function of aged mice. Transcriptomics showed that genes related to tricarboxylic acid cycle (TCA) were enriched after treatments. Metabolic analysis showed increased substrates of TCA cycle in both LR and FP supernatants. Muscle mitochondria density, ATP content, NAD[+]/NADH, mitochondrial dynamics and biogenesis proteins, as well as colon tight junction proteins of aged mice were improved by both probiotics. LR and the combination of two probiotics also benefit intestinal immune health by reducing CD8[+] IFNγ[+] T cells. Gut microbiota dysbiosis is a pathogenesis of sarcopenia, and muscle-related probiotics could alleviate age-related muscle disorders mainly through mitochondria improvement. Further clinical translation is warranted.}, }
@article {pmid39827989, year = {2025}, author = {Cheng, CK and Ye, L and Wang, Y and Wang, YL and Xia, Y and Wong, SH and Chen, S and Huang, Y}, title = {Exercised gut microbiota improves vascular and metabolic abnormalities in sedentary diabetic mice through gut‒vascular connection.}, journal = {Journal of sport and health science}, volume = {14}, number = {}, pages = {101026}, pmid = {39827989}, issn = {2213-2961}, abstract = {BACKGROUND: Exercise elicits cardiometabolic benefits, reducing the risks of cardiovascular diseases and type 2 diabetes. This study aimed to investigate the vascular and metabolic effects of gut microbiota from exercise-trained donors on sedentary mice with type 2 diabetes and the potential mechanism.<br><br>METHODS: Leptin receptor-deficient diabetic (db/db) and nondiabetic (db/m[+]) mice underwent running treadmill exercise for 8 weeks, during which fecal microbiota transplantation (FMT) was parallelly performed from exercise-trained to sedentary diabetic (db/db) mice. Endothelial function, glucose homeostasis, physical performance, and vascular signaling of recipient mice were assessed. Vascular and intestinal stresses, including inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, were investigated. RNA sequencing analysis on mouse aortic and intestinal tissues was performed. Gut microbiota profiles of recipient mice were evaluated by metagenomic sequencing.<br><br>RESULTS: Chronic exercise improved vascular and metabolic abnormalities in donor mice. Likewise, FMT from exercised donors retarded body weight gain and slightly improved grip strength and rotarod performance in recipient mice. Exercise-associated FMT enhanced endothelial function in different arteries, suppressed vascular and intestinal stresses, and improved glucose homeostasis in recipient mice, with noted microRNA-181b upregulation in aortas and intestines. Altered gut microbiota profiles and gut-derived factors (e.g., short-chain fatty acids and glucagon-like peptide-1) as well as improved intestinal integrity shall contribute to the cardiometabolic benefits, implying a gut&#x2012;vascular connection.<br><br>CONCLUSION: This proof-of-concept study indicates that exercised microbiota confers cardiometabolic benefits on sedentary db/db mice, extending the beneficial mechanism of exercise through gut&#x2012;vascular communication. The findings open up new therapeutic opportunities for cardiometabolic diseases and shed light on the development of exercise mimetics by targeting the gut microbiota.}, }
@article {pmid39827465, year = {2025}, author = {Zhang, Y and Hao, R and Chen, J and Huang, K and Li, S and Cao, H and Guan, X}, title = {Gut-Derived Ursodeoxycholic Acid from Saponins of Quinoa Regulated Colitis via Inhibiting the TLR4/NF-κB Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {4}, pages = {2415-2429}, doi = {10.1021/acs.jafc.4c09151}, pmid = {39827465}, issn = {1520-5118}, mesh = {*Toll-Like Receptor 4/genetics/metabolism ; Animals ; Gastrointestinal Microbiome/drug effects ; *NF-kappa B/genetics/metabolism ; Humans ; Mice ; *Saponins/administration &amp; dosage/metabolism/chemistry ; *Chenopodium quinoa/chemistry/metabolism ; *Ursodeoxycholic Acid/administration &amp; dosage/metabolism ; *Colitis/drug therapy/genetics/microbiology/metabolism ; Mice, Inbred C57BL ; Male ; Signal Transduction/drug effects ; Caco-2 Cells ; Bacteria/isolation &amp; purification/classification/genetics/metabolism ; *Plant Extracts/administration &amp; dosage ; }, abstract = {Alteration of the gut microbiota and its metabolites plays a key role in the development of inflammatory bowel disease (IBD). Here, we investigated the mechanism of saponins, a byproduct from quinoa (SQ) processing, in regulating IBD. SQ ameliorated gut microbiota dysbiosis revealed by 16S rRNA sequencing and improved colonic antioxidant activities and barrier integrity in dextran sulfate sodium (DSS)-treated mice. Broad-spectrum antibiotics further proved that the gut-protective effects of SQ were mediated by gut microbiota. Next, fecal microbiota transplantation (FMT) of SQ-induced gut microbiota/metabolites to inoculate DSS-treated mice alleviated colitis significantly. Untargeted metabolomics and lipidomics revealed that ursodeoxycholic acid (UDCA) was enriched as a microbial metabolite after SQ supplementation. UDCA was then found to attenuate DSS-induced colitis in vivo by targeting the TLR4/NF-κB pathway, which was also verified in a Caco-2 cell model treated with a TLR4 agonist/antagonist. Overall, our findings established that gut microbiota-UDCA-TLR4/NF-κB signaling plays a key role in mediating the protective effects of SQ.}, }
@article {pmid39826789, year = {2025}, author = {Du, X and Liu, L and Yang, L and Zhang, Y and Dong, K and Li, Y and Chen, Y and Yang, Q and Zhu, X and Li, Q}, title = {Cumulative experience meets modern science: Remarkable effects of TongXieYaoFang formula on facilitating intestinal mucosal healing and secretory function.}, journal = {Journal of ethnopharmacology}, volume = {341}, number = {}, pages = {119370}, doi = {10.1016/j.jep.2025.119370}, pmid = {39826789}, issn = {1872-7573}, mesh = {Animals ; *Intestinal Mucosa/drug effects/pathology/metabolism ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Dextran Sulfate ; Mice ; Mice, Inbred C57BL ; *Wound Healing/drug effects ; Male ; Disease Models, Animal ; *Colitis, Ulcerative/drug therapy/chemically induced/pathology ; *Colitis/drug therapy/chemically induced/pathology ; Colon/drug effects/pathology ; }, abstract = {TongXieYaoFang (TXYF), a classical formula used in Traditional Chinese Medicine, is renowned for its efficacy in treating chronic abdominal pain and diarrhoea. Modern research suggests that fundamental relief from these symptoms depends on complete intestinal mucosal healing, which normalises gut secretory functions. Consensus between traditional and modern medical theories indicates that TXYF is particularly suitable for treating the remission phase of ulcerative colitis (UC). Unfortunately, its potential in the remission phase has not received sufficient attention, and its use has been largely limited to a supportive role during the acute phase.<br><br>AIM OF THE STUDY: This study aimed to elucidate the efficacy of TXYF in promoting intestinal mucosal healing and enhancing gut secretory function during the non-acute damage phase, as well as to identify the underlying mechanisms contributing to its effects.<br><br>METHODS: A mouse model of dextran sulphate sodium salt (DSS)-induced colitis was optimised to specifically evaluate the effects of TXYF on mucosal healing during the repair phase. The effects of TXYF on murine colon function were assessed by measuring faecal pellet count and water content, and further evaluated through immunohistochemical analyses. The underlying mechanisms of action of TXYF were elucidated using mouse intestinal organoid cultures, intestinal stem cell (ISCs) transplantation, immunofluorescence, and western blotting. Active components of TXYF were identified via LC-MS/MS analysis and integrated with network pharmacology for bioinformatics assessment.<br><br>RESULTS: TXYF significantly promoted mucosal healing, as reflected by reduced disease activity scores, increased colon length, enhanced epithelial proliferation, and decreased histological damage. Furthermore, TXYF enhanced the recovery of critical intestinal functions, including barrier integrity, absorption, secretion, and motility. Notably, the improvement in the secretory function was particularly pronounced. Mechanistically, these therapeutic effects were mediated by the upregulation of the Atonal homolog 1/SAM pointed domain containing ETS transcription factor/Mucin 2 pathway, which facilitates the differentiation and maturation of ISCs into goblet cells, thereby contributing to both mucosal repair and enhanced secretory function.<br><br>CONCLUSIONS: Our study demonstrated that TXYF significantly promotes intestinal mucosal healing and enhances secretory function. These findings offer a solid basis for exploring the potential applications of TXYF in UC management during the remission phase.}, }
@article {pmid39826698, year = {2025}, author = {Song, Y and Cui, Y and Zhong, Y and Wang, Y and Zheng, X}, title = {Fecal microbiota transplantation combined with inulin promotes the development and function of early immune organs in chicks.}, journal = {Journal of biotechnology}, volume = {399}, number = {}, pages = {81-90}, doi = {10.1016/j.jbiotec.2025.01.012}, pmid = {39826698}, issn = {1873-4863}, mesh = {Animals ; *Inulin/pharmacology ; *Chickens/immunology/growth &amp; development ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; }, abstract = {Modern management of chicks hinders the vertical transmission of intestinal microbiota, which is closely related to immunity. Inulin is a substrate that can be utilized by the microbiota. This study aimed to determine whether fecal microbiota transplantation (FMT) combined with inulin played a "1 + 1 > 2" role in enhancing the development and function of immune organs. Chicks were treated with 1 % inulin and/or fecal microbiota suspension on days 1-6. The growth performance, immune organ development, and immune indicators were evaluated on days 7, 14, and 21. Results showed that the combination of FMT and inulin significantly increased the immune organ index on day 7 and promoted the morphological structure and the expression of proliferating cell nuclear antigen (PCNA) in immune organs on days 7, 14, and 21. Each treatment increased the gene expression of interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-2 (IL-2), B cell-activating factor receptor (BAFFR), B cell linker (BLNK), C-X-C Motif Chemokine Ligand 12 (CXCL12), C-X-C Motif Chemokine Receptor 4 (CXCR4), and Biotin (Bu-1) to varying degrees. FMT combined with inulin significantly increased the expression of IgA-positive cells on days 7 and 14. In conclusion, the synergistic effect of FMT and inulin had beneficial impacts on the development and function of immune organs.}, }
@article {pmid39826450, year = {2025}, author = {Zhu, Z and Zuo, S and Zhu, Z and Wang, C and Du, Y and Chen, F}, title = {THSWD upregulates the LTF/AMPK/mTOR/Becn1 axis and promotes lysosomal autophagy in hepatocellular carcinoma cells by regulating gut flora and metabolic reprogramming.}, journal = {International immunopharmacology}, volume = {148}, number = {}, pages = {114091}, doi = {10.1016/j.intimp.2025.114091}, pmid = {39826450}, issn = {1878-1705}, mesh = {*Carcinoma, Hepatocellular/drug therapy/pathology/metabolism ; *Liver Neoplasms/drug therapy/pathology/metabolism ; Animals ; *Gastrointestinal Microbiome/drug effects ; Humans ; TOR Serine-Threonine Kinases/metabolism ; Autophagy/drug effects ; AMP-Activated Protein Kinases/metabolism ; Mice ; Beclin-1/metabolism ; Lysosomes/metabolism/drug effects ; Signal Transduction/drug effects ; Cell Line, Tumor ; Male ; Up-Regulation ; Apoptosis/drug effects ; Metabolic Reprogramming ; }, abstract = {THSWD has the effect of reducing inflammation, improving microcirculation, and regulating immune status in patients with hepatocellular carcinoma. Regardless of its clear therapeutic effect, the underlying mechanism of action against hepatocellular carcinoma is not clear. To identify critical gut microbiota and its associated metabolites related to THSWD inhibition against hepatocellular carcinoma progression, we assessed the microbe-dependent anti-hepatocellular carcinoma effects of THSWD through 16 s rRNA gene sequencing, fecal microbial transplantation and antibiotic treatment. Metabolic analyses, transcriptomic analyses, and molecular experiments were performed to explore how THSWD modulates the gut microbiota against hepatocellular carcinoma progression. As confirmed by in vivo and in vitro assays, THSWD reduced tumour growth rate and promoted apoptosis in hepatocellular carcinoma cells in hepatocellular carcinoma model mice, and liver and kidney indexes were detected and confirmed the safety of THSWD. Transcriptomic analysis revealed that the targets of THSWD were significantly enriched in multiple lysosomal autophagy signalling pathways, suggesting that lysosomal autophagy is probably associated with THSWD's therapeutic effect. Based on the integrated data analysis, THSWD delays hepatocellular carcinoma progression by increasing the intestinal microbiota Duncaniella and augmenting the metabolite glabrol, and the joint analysis of metabolic and genomic data suggests that this metabolite is associated with lysosomal autophagy, and cellular experiments confirmed that the The differential metabolite glabrol induces apoptosis in hepatocellular carcinoma cells by triggering the lysosomal autophagy-mediated apoptosis signalling pathway. Supplementation with glabrol metabolites up regulates the LTF/AMPK/mTOR/Beclin1 axis and promotes hepatocellular carcinoma cells with lysosomal autophagy and induced apoptosis in hepatocellular carcinoma cells.}, }
@article {pmid39826104, year = {2025}, author = {Lin, A and Jiang, A and Huang, L and Li, Y and Zhang, C and Zhu, L and Mou, W and Liu, Z and Zhang, J and Cheng, Q and Wei, T and Luo, P}, title = {From chaos to order: optimizing fecal microbiota transplantation for enhanced immune checkpoint inhibitors efficacy.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2452277}, doi = {10.1080/19490976.2025.2452277}, pmid = {39826104}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; *Gastrointestinal Microbiome ; *Neoplasms/therapy/immunology/microbiology ; Animals ; Tumor Microenvironment ; Immunotherapy/methods ; Treatment Outcome ; }, abstract = {The integration of fecal microbiota transplantation (FMT) with immune checkpoint inhibitors (ICIs) presents a promising approach for enhancing cancer treatment efficacy and overcoming therapeutic resistance. This review critically examines the controversial effects of FMT on ICIs outcomes and elucidates the underlying mechanisms. We investigate how FMT modulates gut microbiota composition, microbial metabolite profiles, and the tumor microenvironment, thereby influencing ICIs effectiveness. Key factors influencing FMT efficacy, including donor selection criteria, recipient characteristics, and administration protocols, are comprehensively discussed. The review delineates strategies for optimizing FMT formulations and systematically monitoring post-transplant microbiome dynamics. Through a comprehensive synthesis of evidence from clinical trials and preclinical studies, we elucidate the potential benefits and challenges of combining FMT with ICIs across diverse cancer types. While some studies report improved outcomes, others indicate no benefit or potential adverse effects, emphasizing the complexity of host-microbiome interactions in cancer immunotherapy. We outline critical research directions, encompassing the need for large-scale, multi-center randomized controlled trials, in-depth microbial ecology studies, and the integration of multi-omics approaches with artificial intelligence. Regulatory and ethical challenges are critically addressed, underscoring the imperative for standardized protocols and rigorous long-term safety assessments. This comprehensive review seeks to guide future research endeavors and clinical applications of FMT-ICIs combination therapy, with the potential to improve cancer patient outcomes while ensuring both safety and efficacy. As this rapidly evolving field advances, maintaining a judicious balance between openness to innovation and cautious scrutiny is crucial for realizing the full potential of microbiome modulation in cancer immunotherapy.}, }
@article {pmid39825784, year = {2025}, author = {Zhang, R and Sun, X and Lu, H and Zhang, X and Zhang, M and Ji, X and Yu, X and Tang, C and Wu, Z and Mao, Y and Zhu, J and Ji, M and Yang, Z}, title = {Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway.}, journal = {Microbial biotechnology}, volume = {18}, number = {1}, pages = {e70083}, pmid = {39825784}, issn = {1751-7915}, support = {2024YQFH05//"YiQi''funding project/ ; }, mesh = {Gastrointestinal Microbiome/drug effects ; Animals ; *Proto-Oncogene Proteins c-akt/metabolism ; *Phosphatidylinositol 3-Kinases/metabolism ; *Chemical and Drug Induced Liver Injury/prevention &amp; control ; *Disulfiram/pharmacology/therapeutic use ; Signal Transduction/drug effects ; Male ; Mice ; RNA, Ribosomal, 16S/genetics ; Akkermansia ; Acetaminophen/adverse effects ; Fecal Microbiota Transplantation ; Hepatocytes/drug effects ; Apoptosis/drug effects ; Disease Models, Animal ; }, abstract = {Acetaminophen induced acute liver injury (ALI) has a high incidence and is a serious medical problem, but there is a lack of effective treatment. The enterohepatic axis is one of the targets of recent attention due to its important role in liver diseases. Disulfiram (DSF) is a multitarget drug that has been proven to play a role in a variety of liver diseases and can affect intestinal flora, but whether it can alleviate ALI is not clear. We utilised bacterial 16S rRNA gene profiling, antimicrobial treatments, and faecal microbiota transplantation tests to explore whether DSF therapy for ALI is dependent on gut microbiota. Our findings indicate that DSF primarily restores intestinal microbiome balance by modulating the abundance of Akkermansia muciniphila (A. muciniphila), leading to significant alleviation of ALI symptoms in a gut microbiota dependent manner. We also found that A. muciniphila can promote the activation of PI3K/Akt pathway, correct the Bcl-2/Bax ratio, and further inhibit hepatocyte apoptosis. In conclusion, DSF ameliorates ALI by modulating the intestinal microbiome and activating the PI3K/AKT pathway through A. muciniphila.}, }
@article {pmid39824679, year = {2024}, author = {Elyas, S and Barata, P and Vaishampayan, U}, title = {Clinical Applications of Microbiome in Renal Cell Carcinoma.}, journal = {European urology focus}, volume = {10}, number = {6}, pages = {898-901}, doi = {10.1016/j.euf.2024.12.006}, pmid = {39824679}, issn = {2405-4569}, mesh = {Humans ; *Carcinoma, Renal Cell/therapy/microbiology ; *Kidney Neoplasms/therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Probiotics/therapeutic use ; Immune Checkpoint Inhibitors/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics ; }, abstract = {Advancements in microbiome research reveal its impact on cancer treatment outcomes, particularly in renal cell carcinoma (RCC). While immune checkpoint inhibitors (ICIs) have improved survival in metastatic RCC, composition of the gut microbiome has the potential to influence their efficacy. Antibiotic-induced microbiome disruptions correlate with diminished outcomes, while strains such as Akkermansia muciniphila, Clostridium butyricum, and others enhance immune responses and progression-free survival. Some prebiotics such as inulin gel can alter the gut flora to overcome the resistant strains occurring in response to immune therapy. This mini-review explores microbiome-targeted interventions, such as pre/probiotics and fecal microbiota transplantation, for overcoming ICI resistance. Although promising, prospective randomized trials are needed to standardize clinical applications and optimize microbiome-targeted treatments. The standard use of gut-modulating therapy cannot be recommended at present outside of clinical trials. A double-blind placebo-controlled randomized trial of ICI ± gut modulating therapy is being planned in frontline therapy of advanced RCC (BIOFRONT trial by the Southwest Oncology Group).}, }
@article {pmid39821840, year = {2025}, author = {Vinterberg, JE and Oddsdottir, J and Nye, M and Pinton, P}, title = {Management of Recurrent Clostridioides difficile Infection (rCDI): A Systematic Literature Review to Assess the Feasibility of Indirect Treatment Comparison (ITC).}, journal = {Infectious diseases and therapy}, volume = {14}, number = {2}, pages = {327-355}, pmid = {39821840}, issn = {2193-8229}, abstract = {Recurrent Clostridioides difficile infection (rCDI) is a major cause of increased morbidity, mortality, and healthcare costs. Fecal-microbiota-based therapies are recommended for rCDI on completion of standard-of-care (SoC) antibiotics to prevent further recurrence: these therapies include conventional fecal-microbiota transplantation and the US Food and Drug Administration-approved therapies REBYOTA® (RBL) and VOWST Oral Spores™ (VOS). As an alternative to microbiota-based therapies, bezlotoxumab, a monoclonal antibody, is used as adjuvant to SoC antibiotics to prevent rCDI. There are no head-to-head clinical trials comparing different microbiota-based therapies or bezlotoxumab for rCDI. To address this gap, we conducted a systematic literature review to identify clinical trials on rCDI treatments and assess the feasibility of using them to conduct an indirect treatment comparison (ITC). The feasibility analysis determined that trial heterogeneity, particularly relating to inclusion criteria, may significantly compromise ITC and prevent cross-trial comparisons. Our analysis underlines the need to adopt standardized protocols to ensure comparability across trials.}, }
@article {pmid39821715, year = {2025}, author = {Berry, P and Khanna, S}, title = {The evolving landscape of live biotherapeutics in the treatment of Clostridioides difficile infection.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {44}, number = {2}, pages = {129-141}, pmid = {39821715}, issn = {0975-0711}, mesh = {Humans ; *Clostridium Infections/therapy/epidemiology/microbiology ; *Fecal Microbiota Transplantation/methods ; *Biological Therapy/methods ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; Gastrointestinal Microbiome ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridioides difficile (C. difficile) infection (CDI) is common after antibiotic exposure and presents significant morbidity, mortality and healthcare costs worldwide. The rising incidence of recurrent CDI, driven by hypervirulent strains, widespread antibiotic use and increased community transmission, has led to an urgent need for novel therapeutic strategies. Conventional antibiotic treatments, although effective, face limitations due to rising antibiotic resistance and high recurrence rates, which can reach up to 60% after multiple infections. This has prompted exploration of alternative therapies such as fecal microbiota-based therapies, including fecal microbiota transplantation (FMT) and live biotherapeutics (LBPs), which demonstrate superior efficacy in preventing recurrence. They are aimed at restoring the gut microbiota. Fecal microbiota, live-jslm and fecal microbiota spores, live-brpk have been approved by the U.S. Food and Drug Administration in individuals aged 18 years or older for recurrent CDI after standard antimicrobial treatment. They have demonstrated high efficacy and a favorable safety profile in clinical trials. Another LBP under study includes VE-303, which is not derived from human donor stool. This review provides a comprehensive overview of the current therapeutic landscape for CDI, including its epidemiology, pathophysiology, risk factors, diagnostic modalities and treatment strategies. The review delves into the emerging role of live biotherapeutics, with a particular focus on fecal microbiota-based therapies. We explore their development, mechanisms of action, clinical applications and potential to revolutionize CDI management.}, }
@article {pmid39821305, year = {2025}, author = {Shi, L and Duan, Y and Fang, N and Zhang, N and Yan, S and Wang, K and Hou, T and Wang, Z and Jiang, X and Gao, Q and Zhang, S and Li, Y and Zhang, Y and Gong, Y}, title = {Lactobacillus gasseri prevents ibrutinib-associated atrial fibrillation through butyrate.}, journal = {Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology}, volume = {27}, number = {2}, pages = {}, pmid = {39821305}, issn = {1532-2092}, support = {HMUMIF-22001//HMU Marshal Initiative Funding/ ; No. 81974024, No. 82200413, and No. 82300430//National Natural Science Foundation of China/ ; HYD2020J00001//First Affiliated Hospital of Harbin Medical University/ ; HMUMIF-22001//Heilongjiang Province 'Jiebang guashuai' Science and Technology Research/ ; //Excellent Young Medical Talents Training Fund/ ; }, mesh = {Animals ; Adenine/analogs &amp; derivatives ; *Atrial Fibrillation/prevention &amp; control/chemically induced/microbiology/physiopathology/metabolism ; *Gastrointestinal Microbiome/drug effects ; Piperidines ; Disease Models, Animal ; Male ; *Butyrates/pharmacology/metabolism ; *Lactobacillus gasseri/growth &amp; development/metabolism ; Dysbiosis ; Fecal Microbiota Transplantation ; *Pyrazoles ; *Pyrimidines ; Rats, Sprague-Dawley ; Rats ; *Protein Kinase Inhibitors ; Reactive Oxygen Species/metabolism ; Heart Rate/drug effects ; Heart Atria/physiopathology/drug effects/metabolism ; }, abstract = {BACKGROUND: Ibrutinib, a widely used anti-cancer drug, is known to significantly increase the susceptibility to atrial fibrillation (AF). While it is recognized that drugs can reshape the gut microbiota, influencing both therapeutic effectiveness and adverse events, the role of gut microbiota in ibrutinib-induced AF remains largely unexplored.<br><br>METHOD: Utilizing 16S rRNA gene sequencing, faecal microbiota transplantation, metabonomics, electrophysiological examination, and molecular biology methodologies, we sought to validate the hypothesis that gut microbiota dysbiosis promotes ibrutinib-associated AF and to elucidate the underlying mechanisms.<br><br>RESULT: We found that ibrutinib administration pre-disposes rats to AF. Interestingly, ibrutinib-associated microbial transplantation conferred increased susceptibility to AF in rats. Notably, ibrutinib induced a significantly decrease in the abundance of Lactobacillus gasseri (L. gasseri), and oral supplementation of L. gasseri or its metabolite, butyrate (BA), effectively prevented rats from ibrutinib-induced AF. Mechanistically, BA inhibits the generation of reactive oxygen species, thereby ameliorating atrial structural remodelling. Furthermore, we demonstrated that ibrutinib inhibited the growth of L. gasseri by disrupting the intestinal barrier integrity.<br><br>CONCLUSION: Collectively, our findings provide compelling experimental evidence supporting the potential efficacy of targeting gut microbes in preventing ibrutinib-associated AF, opening new avenues for therapeutic interventions.}, }
@article {pmid39816955, year = {2025}, author = {Wang, Q and Ji, J and Xiao, S and Wang, J and Yan, X and Fang, L}, title = {Explore Alteration of Lung and Gut Microbiota in a Murine Model of OVA-Induced Asthma Treated by CpG Oligodeoxynucleotides.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {445-461}, pmid = {39816955}, issn = {1178-7031}, abstract = {AIM: We sought to investigate the impact of CpG oligodeoxynucleotides (CpG-ODN) administration on the lung and gut microbiota in asthmatic mice, specifically focusing on changes in composition, diversity, and abundance, and to elucidate the microbial mechanisms underlying the therapeutic effects of CpG-ODN and identify potential beneficial bacteria indicative of its efficacy.<br><br>METHODS: HE staining were used to analyze inflammation in lung, colon and small intestine tissues. High-throughput sequencing technology targeting 16S rRNA was employed to analyze the composition, diversity, and correlation of microbiome in the lung, colon and small intestine of control, model and CpG-ODN administration groups.<br><br>RESULTS: (1) Histopathologically, both lung and intestinal tissue in asthmatic mice exhibited significant structural damage and inflammatory response, whereas the structure of both lung and intestinal tissue approached normal levels, accompanied by a notable improvement in the inflammatory response after CpG-ODN treatment. (2) In the specific microbiota composition analysis, bacterial dysbiosis observed in the asthmatic mice, accompanied by enrichment of Proteobacteria found to cause lung and intestinal epithelial damage and inflammatory reaction. After CpG-ODN administration, bacterial dysbiosis was improved, and a notable enrichment of beneficial bacteria, indicating a novel microecology. Meanwhile Oscillospira and Clostridium were identified as two biomarkers of the CpG-ODN treatment. (3) Heatmap analysis revealed significant correlations among lung, small intestine, and colon microbiota.<br><br>CONCLUSION: CpG-ODN treatment can ameliorate OVA-induced asthma in mice. One side, preserving the structural integrity of the lung and intestine, safeguarding the mucosal physical barrier, the other side, improving the dysbiosis of lung and gut microbiota in asthmatic mice. Beneficial bacteria and metabolites take up microecological advantages, regulate immune cells and participate in the mucosal immune response to protect the immune barrier. Meanwhile, Oscillospira and Clostridium as biomarkers for CpG-ODN treatment, has reference significance for exploring precise Fecal microbiota transplantation treatment for asthma.}, }
@article {pmid39814666, year = {2025}, author = {Shekhar, S and Schwarzer, M and Dhariwal, A and Petersen, FC}, title = {Nasal microbiota transplantation: a gateway to novel treatments.}, journal = {Trends in microbiology}, volume = {33}, number = {3}, pages = {264-267}, doi = {10.1016/j.tim.2024.12.010}, pmid = {39814666}, issn = {1878-4380}, mesh = {Humans ; *Sinusitis/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Rhinitis/therapy/microbiology ; *Microbiota ; Chronic Disease/therapy ; *Nose/microbiology ; }, abstract = {Two recent studies have highlighted the potential of nasal microbiota transplantation (NMT) to treat chronic rhinosinusitis (CRS). Here we evaluate these findings and propose that lessons from fecal microbiota transplantation (FMT) could guide NMT development, with possible implications for combating antimicrobial resistance in respiratory infections.}, }
@article {pmid39813598, year = {2025}, author = {Ren, M and Xia, Y and Pan, H and Zhou, X and Yu, M and Ji, F}, title = {Duodenal-jejunal bypass ameliorates MASLD in rats by regulating gut microbiota and bile acid metabolism through FXR pathways.}, journal = {Hepatology communications}, volume = {9}, number = {2}, pages = {}, pmid = {39813598}, issn = {2471-254X}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Rats ; *Bile Acids and Salts/metabolism ; *Duodenum/surgery ; Male ; *Receptors, Cytoplasmic and Nuclear/metabolism ; *Jejunum/surgery ; Fecal Microbiota Transplantation ; Rats, Sprague-Dawley ; Disease Models, Animal ; Diet, High-Fat/adverse effects ; Insulin Resistance ; *Fatty Liver/metabolism/surgery ; *Bariatric Surgery/methods ; }, abstract = {BACKGROUND: Although bariatric and metabolic surgical methods, including duodenal-jejunal bypass (DJB), were shown to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical trials and experimental rodent models, their underlying mechanisms remain unclear. The present study therefore evaluated the therapeutic effects and mechanisms of action of DJB in rats with MASLD.<br><br>METHODS: Rats with MASLD were randomly assigned to undergo DJB or sham surgery. Rats were orally administered a broad-spectrum antibiotic cocktail (Abx) or underwent fecal microbiota transplantation to assess the role of gut microbiota in DJB-induced improvement of MASLD. Gut microbiota were profiled by 16S rRNA gene sequencing and metagenomic sequencing, and bile acids (BAs) were analyzed by BA-targeted metabolomics.<br><br>RESULTS: DJB alleviated hepatic steatosis and insulin resistance in rats with diet-induced MASLD. Abx depletion of bacteria abrogated the ameliorating effects of DJB on MASLD. Fecal microbiota transplantation from rats that underwent DJB improved MASLD in high-fat diet-fed recipients by reshaping the gut microbiota, especially by significantly reducing the abundance of Clostridium. This, in turn, suppressed secondary BA biosynthesis and activated the hepatic BA receptor, farnesoid X receptor. Inhibition of farnesoid X receptor attenuated the ameliorative effects of post-DJB microbiota on MASLD.<br><br>CONCLUSIONS: DJB ameliorates MASLD by regulating gut microbiota and BA metabolism through hepatic farnesoid X receptor pathways.}, }
@article {pmid39812804, year = {2025}, author = {Sobral, J and Empadinhas, N and Esteves, AR and Cardoso, SM}, title = {Impact of Nutrition on the Gut Microbiota: Implications for Parkinson's Disease.}, journal = {Nutrition reviews}, volume = {83}, number = {4}, pages = {713-727}, doi = {10.1093/nutrit/nuae208}, pmid = {39812804}, issn = {1753-4887}, support = {//Portuguese national funds/ ; //FCT/ ; PTDC/MED-NEU/3644/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; }, mesh = {Humans ; *Parkinson Disease/microbiology ; *Gastrointestinal Microbiome/physiology ; *Nutritional Status ; *Diet ; Diet, Ketogenic ; Diet, Mediterranean ; }, abstract = {Parkinson's disease (PD) is a multifactorial neurodegenerative disease that is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and by the anomalous accumulation of α-synuclein aggregates into Lewy bodies and Lewy neurites. Research suggests 2 distinct subtypes of PD: the brain-first subtype if the pathology arises from the brain and then spreads to the peripheral nervous system (PNS) and the body-first subtype, where the pathological process begins in the PNS and then spreads to the central nervous system. This review primarily focuses on the body-first subtype. The influence of the gut microbiota on the development of PD has been the subject of growing interest among researchers. It has been suggested that gut inflammation may be closely associated with pathogenesis in PD, therefore leading to the hypothesis that gut microbiota modulation could play a significant role in this process. Nutrition can influence gut health and alter the risk and progression of PD by altering inflammatory markers. This review provides an overview of recent research that correlates variations in gut microbiota composition between patients with PD and healthy individuals with the impact of certain nutrients and dietary patterns, including the Mediterranean diet, the Western diet, and the ketogenic diet. It explores how these diets influence gut microbiota composition and, consequently, the risk of PD. Last, it examines fecal transplantation and the use of prebiotics, probiotics, or synbiotics as potential therapeutic strategies to balance the gut microbiome, aiming to reduce the risk or delay the progression of PD.}, }
@article {pmid39812540, year = {2025}, author = {Cerna, C and Vidal-Herrera, N and Silva-Olivares, F and Álvarez, D and González-Arancibia, C and Hidalgo, M and Aguirre, P and González-Urra, J and Astudillo-Guerrero, C and Jara, M and Porras, O and Cruz, G and Hodar, C and Llanos, P and Urrutia, P and Ibacache-Quiroga, C and Nevzorova, Y and Cubero, FJ and Fuenzalida, M and Thomas-Valdés, S and Jorquera, G}, title = {Fecal Microbiota Transplantation from Young-Trained Donors Improves Cognitive Function in Old Mice Through Modulation of the Gut-Brain Axis.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.1089}, pmid = {39812540}, issn = {2152-5250}, abstract = {The gut-brain axis is a bidirectional communication pathway that modulates cognitive function. A dysfunctional gut-brain axis has been associated with cognitive impairments during aging. Therefore, we propose evaluating whether modulation of the gut microbiota through fecal microbiota transplantation (FMT) from young-trained donors (YT) to middle-aged or aged mice could enhance brain function and cognition in old age. Twelve-month-old male mice received an initial FMT from YT (YT-Tr) or age-matched donors (Auto-Tr) following antibiotic treatment. Three months later, the mice received a second FMT as reinforcement. Additionally, 18-month-old mice received Auto-Tr, YT-Tr, or FMT from young sedentary donors (YS-Tr). Cognitive function was assessed using novel object recognition and object location memory tests. Long-term potentiation (LTP) in hippocampal brain slices was studied, while neuroinflammation and synaptic plasticity were analyzed in hippocampal samples via qPCR and immunoblot. Gut permeability was evaluated in ileum and colon sections, serum samples were analyzed for cytokine levels, and fecal samples were used to measure short-chain fatty acid (SCFA) levels and perform 16S rRNA gene sequencing. We observed that YT-Tr, whether performed in middle age or old age, improved cognitive function in aged mice. Recognition and spatial memory were significantly enhanced in YT-Tr mice compared to Auto-Tr and YS-Tr groups. Intact LTP was observed in YT-Tr mice at 18 months of age, whereas LTP was impaired in the Auto-Tr group. Neuroinflammation was reduced, and synaptic plasticity modulators such as PSD-95 and FNDC5/Irisin were upregulated in the hippocampus of YT-Tr mice compared to both YS-Tr and Auto-Tr groups. A significant reduction in ileal and colon permeability was detected in YT-Tr animals, along with elevated cecal levels of butyrate and valerate compared to Auto-Tr. Moreover, YT-Tr decreased pro-inflammatory factors and increased anti-inflammatory factors in the serum of aged mice. Beta diversity analysis revealed significant differences in microbial community composition between YT-Tr and Auto-Tr animals, with higher abundances of Akkermansia, Prevotellaceae_UCG-001, and Odoribacter in YT-Tr mice. In conclusion, our study demonstrates that FMT from young-trained donors improves cognitive function and synaptic plasticity by modulating gut permeability, inflammation, SCFA levels, and gut microbiota composition in aged mice.}, }
@article {pmid39812347, year = {2025}, author = {Gustafson, KL and Rodriguez, TR and McAdams, ZL and Coghill, LM and Ericsson, AC and Franklin, CL}, title = {Failure of colonization following gut microbiota transfer exacerbates DSS-induced colitis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447815}, pmid = {39812347}, issn = {1949-0984}, support = {T32 GM008396/GM/NIGMS NIH HHS/United States ; T32 OD011126/OD/NIH HHS/United States ; U42 OD010918/OD/NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Dextran Sulfate/adverse effects ; *Colitis/chemically induced/microbiology/pathology ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Feces/microbiology ; Bacteria/classification/genetics/isolation &amp; purification/growth &amp; development ; Female ; Embryo Transfer ; Specific Pathogen-Free Organisms ; Male ; }, abstract = {To study the impact of differing specific pathogen-free gut microbiomes (GMs) on a murine model of inflammatory bowel disease, selected GMs were transferred using embryo transfer (ET), cross-fostering (CF), and co-housing (CH). Prior work showed that the GM transfer method and the microbial composition of donor and recipient GMs can influence microbial colonization and disease phenotypes in dextran sodium sulfate-induced colitis. When a low richness GM was transferred to a recipient with a high richness GM via CH, the donor GM failed to successfully colonize, and a more severe disease phenotype resulted when compared to ET or CF, where colonization was successful. By comparing CH and gastric gavage for fecal material transfer, we isolated the microbial component of this effect and determined that differences in disease severity and survival were associated with microbial factors rather than the transfer method itself. Mice receiving a low richness GM via CH and gastric gavage exhibited greater disease severity and higher expression of pro-inflammatory immune mediators compared to those receiving a high richness GM. This study provides valuable insights into the role of GM composition and colonization in disease modulation.}, }
@article {pmid39812329, year = {2025}, author = {Zhang, Y and Wang, A and Zhao, W and Qin, J and Zhang, Y and Liu, B and Yao, C and Long, J and Yuan, M and Yan, D}, title = {Microbial succinate promotes the response to metformin by upregulating secretory immunoglobulin a in intestinal immunity.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2450871}, pmid = {39812329}, issn = {1949-0984}, mesh = {Animals ; *Metformin/pharmacology ; *Immunoglobulin A, Secretory/genetics/immunology/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; Humans ; *Succinic Acid/metabolism/pharmacology ; *Intestines/immunology/drug effects/microbiology ; Fecal Microbiota Transplantation ; Diabetes Mellitus, Type 2/drug therapy/immunology/microbiology ; Bacteroides thetaiotaomicron/metabolism ; Up-Regulation ; *Hypoglycemic Agents/pharmacology ; Mice, Inbred C57BL ; Mice, Knockout ; Male ; }, abstract = {Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus; however, many patients respond poorly to this drug in clinical practice. The potential involvement of microbiota-mediated intestinal immunity and related signals in metformin responsiveness has not been previously investigated. In this study, we successfully constructed a humanized mouse model by fecal transplantation of the gut microbiota from clinical metformin-treated - responders and non-responders, and reproduced the difference in clinical phenotypes of responsiveness to metformin. The abundance of Bacteroides thetaiotaomicron, considered a representative differential bacterium of metformin responsiveness, and the level of secretory immunoglobulin A (SIgA) in intestinal immunity increased significantly in responder recipient mice following metformin treatment. In contrast, no significant alterations in B. thetaiotaomicron and SIgA were observed in non-responder recipient mice. The study of IgA[-/-] mice confirmed that downregulated expression or deficiency of SIgA resulted in non-response to metformin, meaning that metformin was unable to improve dysfunctional glucose metabolism and reduce intestinal and adipose tissue inflammation, ultimately leading to systemic insulin resistance. Furthermore, supplementation with succinate, a microbial product of B. thetaiotaomicron, potentially reversed the non-response to metformin by inducing the production of SIgA. In conclusion, we demonstrated that upregulated SIgA, which could be regulated by succinate, was functionally involved in metformin response through its influence on immune cell-mediated inflammation and insulin resistance. Conversely, an inability to regulate SIgA may result in a lack of response to metformin.}, }
@article {pmid39812000, year = {2025}, author = {Zhao, H and Fu, X and Wang, Y and Shang, Z and Li, B and Zhou, L and Liu, Y and Liu, D and Yi, B}, title = {Therapeutic Potential of Vanillic Acid in Ulcerative Colitis Through Microbiota and Macrophage Modulation.}, journal = {Molecular nutrition &amp; food research}, volume = {69}, number = {4}, pages = {e202400785}, doi = {10.1002/mnfr.202400785}, pmid = {39812000}, issn = {1613-4133}, support = {81760587//National Natural Science Foundation of China/ ; 81760731)//National Natural Science Foundation of China/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Colitis, Ulcerative/drug therapy/chemically induced/microbiology ; *Vanillic Acid/pharmacology ; *Macrophages/drug effects ; Male ; Dextran Sulfate ; Mice ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Cytokines/metabolism ; Akkermansia ; }, abstract = {This study investigated the protective effects of the dietary polyphenol vanillic acid (VA) on dextran sulfate sodium-induced acute ulcerative colitis (UC) in mice, focusing on its impact on the gut microbiota and inflammatory responses. VA was supplemented following dextran sulfate sodium administration, and key indicators, including body weight, disease activity index, colon length, spleen index, and inflammatory markers, were assessed. VA supplementation significantly alleviated UC symptoms, preserved intestinal barrier integrity, and reduced pro-inflammatory cytokine levels. Additionally, VA positively altered the gut microbiota composition, promoting beneficial bacteria such as Akkermansia muciniphila while suppressing the arachidonic acid metabolism pathway. Fecal microbiota transplantation confirmed that the VA-modified gut microbiota contributed to these protective effects. VA also facilitated macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, further mitigating inflammation. These findings highlight the potential of VA as a natural dietary intervention for UC, emphasizing its role in regulating the gut microbiota and inflammatory pathways, which may have significant nutritional relevance in managing inflammatory bowel diseases.}, }
@article {pmid39811933, year = {2025}, author = {Zhang, L and Wang, K and Huang, L and Deng, B and Chen, C and Zhao, K and Wang, W}, title = {Ganoderic Acid A Alleviates Severe Acute Pancreatitis by Modulating Gut Homeostasis and Inhibiting TLR4-NLRP3 Signaling.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {2}, pages = {1563-1579}, pmid = {39811933}, issn = {1520-5118}, mesh = {Animals ; *Toll-Like Receptor 4/genetics/metabolism ; Mice ; *Pancreatitis/drug therapy/genetics/metabolism/microbiology ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Male ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism ; Humans ; Gastrointestinal Microbiome/drug effects ; Homeostasis/drug effects ; Rats ; Mice, Knockout ; Heptanoic Acids ; Lanosterol/analogs &amp; derivatives ; }, abstract = {Background Severe acute pancreatitis (SAP) manifests as a critical state marked by acute abdominal symptoms, often associated with intestinal barrier dysfunction, exacerbating SAP retroactively. Ganoderic acid A (GAA) demonstrates anti-inflammatory properties in various inflammatory disorders. Nonetheless, its potential therapeutic impact on SAP and the underlying mechanisms remain unexplored. Methods In both wild-type and TLR4[-/-] mice, experimental SAP was induced using caerulein plus lipopolysaccharide. Caerulein injections were administered intraperitoneally following 7 days of intragastric GAA administration. Additionally, the potential mechanisms by which GAA ameliorates SAP were further investigated using fecal microbiota transplantation and TLR4-overexpressing IEC-6 cells. Results We observed that GAA treatment significantly ameliorated serum levels of amylase, lipase, and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in SAP mice. Pretreatment with GAA mitigated pathological injuries and reduced M1 macrophage and neutrophil infiltration in pancreatic or ileal tissues. Additionally, GAA treatment down-regulated TLR4-MAPK/NF-κB signaling and NLRP3 inflammasome activation in the pancreatic and ileal tissues of SAP mice. The results further revealed that the gavage of GAA decreased bacterial translocation (Escherichia coli and EUB338), repaired intestinal barrier dysfunction (ZO-1, occludin, DAO, and FITC), increased lysozyme and MUC2 expression, and raised the levels of short-chain fatty acids. Analysis of the gut microbiome showed that the beneficial effects of GAA treatment were associated with improvements in pancreatitis-associated gut microbiota dysbiosis, characterized by notable increases in α-diversity and the abundance of probiotics such as Akkermansia, GCA-900066575, and Parvibacter. Fecal transplantation experiments further confirmed that GAA exerts protective effects by modulating intestinal flora. The protective role of GAA in intestinal and pancreatic injuries is mediated by the inhibition of TLR4 signaling, as further evidenced in TLR4-deficient mice and TLR4-overexpressed IEC-6 cells. The results of docking indicated that GAA interacts with TLR4 via a hydrophobic interaction. Conclusions The study demonstrates that GAA significantly alleviates SAP through its anti-inflammatory and antioxidant capacities, as well as by restoring intestinal homeostasis, thereby providing insights into novel treatments for SAP.}, }
@article {pmid39811913, year = {2025}, author = {Ribeiro, G and Schellekens, H and Cuesta-Marti, C and Maneschy, I and Ismael, S and Cuevas-Sierra, A and Martínez, JA and Silvestre, MP and Marques, C and Moreira-Rosário, A and Faria, A and Moreno, LA and Calhau, C}, title = {A menu for microbes: unraveling appetite regulation and weight dynamics through the microbiota-brain connection across the lifespan.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {328}, number = {3}, pages = {G206-G228}, doi = {10.1152/ajpgi.00227.2024}, pmid = {39811913}, issn = {1522-1547}, support = {UIDB/4255/2020//Centro de Investiga&#x00E7;&#x00E3;o em Tecnologias e Servi&#x00E7;os de Sa&#x00FA;de (CINTESIS)/ ; UIDP/4255/2020//Centro de Investiga&#x00E7;&#x00E3;o em Tecnologias e Servi&#x00E7;os de Sa&#x00FA;de (CINTESIS)/ ; UIDP/04923/2020//Comprehensive Health Research Centre/ ; UIDB/04923/2020//Comprehensive Health Research Centre/ ; SFI/12/RC/2273 _P2//Science Foundation Ireland (SFI)/ ; TC20180025//Food for Health Ireland EI Technology Centre/ ; GOIPG/2023/4836//Irish Research Council (IrishResearch)/ ; CD22/00011//Ministerio de Ciencia e Innovaci&#x00F3;n (MCIN)/ ; MV23/00115//Instituto Carlos III de Salud/ ; Y2020/6600//Comunidad de Madrid (Community of Madrid)/ ; 2020.06333.BD//Fundacao para a Ciencia e a Technologia/ ; }, mesh = {Humans ; *Appetite Regulation/physiology ; *Gastrointestinal Microbiome/physiology ; *Brain/physiology/metabolism ; *Obesity/microbiology/physiopathology/metabolism ; Animals ; *Appetite/physiology ; *Body Weight/physiology ; *Brain-Gut Axis ; Longevity ; }, abstract = {Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior. Therefore, the role of the microbiota-gut-brain axis in appetite and obesity is receiving increased attention. Omics approaches such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics in appetite and weight regulation offer new opportunities for featuring obesity phenotypes. Furthermore, gut-microbiota-targeted approaches such as pre-, pro-, post-, and synbiotic, personalized nutrition, and fecal microbiota transplantation are novel avenues for precision treatments. The aim of this narrative review is 1) to provide an overview of the role of the microbiota-gut-brain axis in appetite regulation across the lifespan and 2) to discuss the potential of omics and gut microbiota-targeted approaches to deepen understanding of appetite regulation and obesity.}, }
@article {pmid39811513, year = {2025}, author = {Wang, Y and Liu, J}, title = {Interplay between creeping fat and gut microbiota: A brand-new perspective on fecal microbiota transplantation in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {2}, pages = {100024}, pmid = {39811513}, issn = {2219-2840}, mesh = {*Fecal Microbiota Transplantation/adverse effects/methods ; *Crohn Disease/therapy/microbiology/pathology/immunology ; *Gastrointestinal Microbiome/immunology/physiology ; Humans ; Animals ; *Dysbiosis/microbiology/therapy ; *Adipose Tissue/pathology ; Disease Models, Animal ; Mice ; *Mesentery/pathology/microbiology ; Intestinal Mucosa/microbiology/pathology ; Recurrence ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease, particularly Crohn's disease (CD), has been linked to modifications in mesenteric adipose tissue (MAT) and the phenomenon known as "creeping fat" (CrF). The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD. Notably, the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence, indicating the significant role of MAT in the pathogenesis of CD. While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD, the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous. This manuscript commentary discusses a recent basic research conducted by Wu et al. In their study, intestinal bacteria from individuals were transplanted into CD model mice, revealing that fecal microbiota transplantation (FMT) from healthy donors alleviated CD symptoms, whereas FMT from CD patients exacerbated these symptoms. Importantly, FMT was found to affect intestinal permeability, barrier function, and the levels of proinflammatory factors and adipokines. Collectively, these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD. However, the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota. Overall, the gut microbiota plays a crucial role in the histopathology of CD, and thus, targeting MAT and CrF may represent a promising avenue for treatment in this patient population.}, }
@article {pmid39811502, year = {2025}, author = {Qiao, T and Wen, XH}, title = {Exploring gut microbiota as a novel therapeutic target in Crohn's disease: Insights and emerging strategies.}, journal = {World journal of gastroenterology}, volume = {31}, number = {2}, pages = {100827}, pmid = {39811502}, issn = {2219-2840}, mesh = {Humans ; *Crohn Disease/therapy/microbiology/pathology/immunology ; *Gastrointestinal Microbiome/immunology/physiology ; Fecal Microbiota Transplantation/methods ; *Dysbiosis/microbiology/therapy/immunology ; Enteral Nutrition/methods ; Disease Progression ; Animals ; }, abstract = {Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets. Creeping fat has been identified as a unique pathological feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome. We characterize this dysbiotic state by identifying key microbiome-bacteria, fungi, viruses, and archaea, and their contributions to CD pathogenesis. Additionally, this paper reviews contemporary therapies, emphasizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions. By elucidating the complex interactions between host-microbiome dynamics and CD pathology, this article aims to advance our understanding of the disease and guide the development of more effective therapeutic strategies for managing CD.}, }
@article {pmid39810863, year = {2024}, author = {Uździcki, AW and Wawrzynowicz-Syczewska, M}, title = {Impact of liver transplantation on intestinal and systemic inflammation markers in patients with colitis ulcerosa concomitant with primary sclerosing cholangitis.}, journal = {Przeglad gastroenterologiczny}, volume = {16}, number = {4}, pages = {439-445}, pmid = {39810863}, issn = {1895-5770}, abstract = {INTRODUCTION: Primary sclerosing cholangitis (PSC) is an uncommon, chronic liver disease characterised by fibrosis and strictures of a bile ducts, causing cholestasis. In the long term it can lead to complete stenosis leading in turn to liver cirrhosis. In patients with severe form of the disease, the recommended treatment is liver transplantation. Because PSC frequently coexists with ulcerative colitis (UC), it is crucial to determine the effect of liver transplantation on the course of UC.<br><br>AIM: The aim was to determine the impact of liver transplantation on intestinal and systemic inflammation markers with UC concomitant with PSC (PSC-UC).<br><br>MATERIAL AND METHODS: Sixty-three patients with PSC-UC were enrolled, 25 of whom underwent liver transplantation (OLTx) due to PSC progression. Clinical symptoms, faecal calprotectin levels, C-reactive protein (CRP) serum concentration, erythrocyte sedimentation rate, and white blood cell count (WBC) were obtained.<br><br>RESULTS: Faecal calprotectin was significantly higher in the post-OLTx group. Mean calprotectin values were 163% higher - 474 ng/ml and 180 ng/ml (p = 0.024) in the post-OLTx group and in the PSC-UC group without the transplantation, respectively. Calprotectin levels exceeded the upper limit of normal (defined as 200 ng/l) in 66% of liver recipients and in 18% of non-transplanted patients (OR = 9.33, p = 0.011). In the post-OLTx group, also CRP concentration (11.01 mg/l vs. 6.54 mg/l, p = 0.30) and WBC (7.58 K/ml vs. 5.72 K/ml, p = 0.006) were higher than in the PSC-UC group without transplantation.<br><br>CONCLUSIONS: We found significantly higher inflammation markers in PSC-UC patients who underwent liver transplantation due to PSC. The effect was strongest in faecal calprotectin levels. In PSC-UC patients after liver transplantation, intensification of UC treatment may be needed, despite the lack of worsening of clinical symptoms.}, }
@article {pmid39809955, year = {2025}, author = {Kumar, D and Bishnoi, M and Kondepudi, KK and Sharma, SS}, title = {Gut Microbiota-Based Interventions for Parkinson's Disease: Neuroprotective Mechanisms and Current Perspective.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39809955}, issn = {1867-1314}, abstract = {Recent evidence links gut microbiota alterations to neurodegenerative disorders, including Parkinson's disease (PD). Replenishing the abnormal composition of gut microbiota through gut microbiota-based interventions "prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT)" has shown beneficial effects in PD. These interventions increase gut metabolites like short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1), which may protect dopaminergic neurons via the gut-brain axis. Neuroprotective effects of these interventions are mediated by several mechanisms, including the enhancement of neurotrophin and activation of the PI3K/AKT/mTOR signaling pathway, GLP-1-mediated gut-brain axis signaling, Nrf2/ARE pathway, and autophagy. Other pathways, such as free fatty acid receptor activation, synaptic plasticity improvement, and blood-brain and gut barrier integrity maintenance, also contribute to neuroprotection. Furthermore, the inhibition of the TLR4/NF-кB pathway, MAPK pathway, GSK-3β signaling pathway, miR-155-5p-mediated neuroinflammation, and ferroptosis could account for their protective effects. Clinical studies involving gut microbiota-based interventions have shown therapeutic benefits in PD patients, particularly in improving gastrointestinal dysfunction and some neurological symptoms. However, the effectiveness in alleviating motor symptoms remains mild. Large-scale clinical trials are still needed to confirm these findings. This review emphasizes the neuroprotective mechanisms of gut microbiota-based interventions in PD as supported by both preclinical and clinical studies.}, }
@article {pmid39809266, year = {2025}, author = {Wang, D and Jiang, Y and Jiang, J and Pan, Y and Yang, Y and Fang, X and Liang, L and Li, H and Dong, Z and Fan, S and Ma, D and Zhang, XS and Li, H and He, Y and Li, N}, title = {Gut microbial GABA imbalance emerges as a metabolic signature in mild autism spectrum disorder linked to overrepresented Escherichia.}, journal = {Cell reports. Medicine}, volume = {6}, number = {1}, pages = {101919}, pmid = {39809266}, issn = {2666-3791}, mesh = {*Autism Spectrum Disorder/microbiology/metabolism ; *Gastrointestinal Microbiome ; Humans ; *gamma-Aminobutyric Acid/metabolism ; Male ; Female ; Animals ; Child ; Mice ; Glutamic Acid/metabolism ; *Escherichia coli ; RNA, Ribosomal, 16S/genetics ; Child, Preschool ; Feces/microbiology ; Adolescent ; Metabolomics/methods ; Metabolome ; }, abstract = {Gut microbiota (GM) alterations have been implicated in autism spectrum disorder (ASD), yet the specific functional architecture remains elusive. Here, employing multi-omics approaches, we investigate stool samples from two distinct cohorts comprising 203 children with mild ASD or typical development. In our screening cohort, regression-based analysis for metabolomic profiling identifies an elevated γ-aminobutyric acid (GABA) to glutamate (Glu) ratio as a metabolic signature of ASD, independent of age and gender. In the validating cohort, we affirm the GABA/Glu ratio as an ASD diagnostic indicator after adjusting for geography, age, gender, and specific food-consuming frequency. Integrated analysis of metabolomics, 16S rRNA sequencing, and metagenomics reveals a correlation between overrepresented Escherichia and disrupted GABA metabolism. Furthermore, we observe social behavioral impairments in weaning mice transplanted with E. coli, suggesting a potential link to ASD symptomatology. Collectively, these findings provide insights into potential diagnostic and therapeutic strategies aimed at evaluating and restoring gut microbial neurotransmitter homeostasis.}, }
@article {pmid39806466, year = {2025}, author = {Khemiri, H and Ben Fraj, I and Lorusso, A and Mekki, N and Mangone, I and Gdoura, M and Di Pasqual, A and Cammà, C and Di Lollo, V and Cherni, A and Touzi, H and Sadraoui, A and Meddeb, Z and Hogga, N and Ben Mustapha, I and Barbouche, MR and Ouederni, M and Triki, H and Haddad-Boubaker, S}, title = {SARS-CoV-2 excretion and genetic evolution in nasopharyngeal and stool samples from primary immunodeficiency and immunocompetent pediatric patients.}, journal = {Virology journal}, volume = {22}, number = {1}, pages = {9}, pmid = {39806466}, issn = {1743-422X}, mesh = {Humans ; *SARS-CoV-2/genetics/isolation &amp; purification/classification ; *COVID-19/virology/immunology ; *Feces/virology ; *Nasopharynx/virology ; Child ; Male ; Female ; RNA, Viral/genetics ; Child, Preschool ; *Virus Shedding ; *Primary Immunodeficiency Diseases/virology ; Adolescent ; Evolution, Molecular ; Infant ; Phylogeny ; Immunocompetence ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Primary Immunodeficiency disorders (PID) can increase the risk of severe COVID-19 and prolonged infection. This study investigates the duration of SARS-CoV-2 excretion and the genetic evolution of the virus in pediatric PID patients as compared to immunocompetent (IC) patients.<br><br>MATERIALS AND METHODS: A total of 40 nasopharyngeal and 24 stool samples were obtained from five PID and ten IC children. RNA detection was performed using RT-qPCR, and whole-genome sequencing was conducted with the NexSeq 1000 platform. Data analysis used the nextflow/viralrecon pipeline. Hotspot amino acid frequencies were investigated using GraphPad Prism v10. Phylodynamic analysis was conducted with BEAST software.<br><br>RESULTS: In IC children, the viral excretion period lasted up to 14 days in nasopharyngeal swabs, with an average duration of 7 days, and ranged from 7 to 14 days in stool samples. In PID patients, the viral RNA was detected in nasopharyngeal for periods between 7 and 28 days, with an average duration of 15 days, and up to 28 days in stool samples. Two SARS-CoV-2 variants were detected in PID patients: Delta (AY.122) and Omicron (BA.1.1). Patients with antibody and combined deficiencies, exhibited the most prolonged shedding periods in both nasopharyngeal and stool samples and one patient presented complications and fatal outcome. Specific Hotspot amino acid changes were detected in PID: A2821V and R550H (ORF1ab).<br><br>CONCLUSION: Our findings underscore the prolonged excretion of SARS-CoV-2 RNA in patients with antibody and combined deficiencies. Thus, specialized care is essential for effectively managing PID patients.}, }
@article {pmid39805780, year = {2024}, author = {Ye, LJ and Xu, XF and Chen, SY and Zhang, H and Gan, YX and Meng, T and Ding, R and Li, J and Cao, G and Wang, KL}, title = {[Regulation of Bifidobacterium-short chain fatty acid metabolism and improvement of intestinal toxicity of vinegar-processed Euphorbiae Pekinensis Radix].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {49}, number = {23}, pages = {6331-6341}, doi = {10.19540/j.cnki.cjcmm.20240912.301}, pmid = {39805780}, issn = {1001-5302}, mesh = {Animals ; Mice ; Humans ; *Acetic Acid/chemistry ; Gastrointestinal Microbiome/drug effects ; *Fatty Acids, Volatile/metabolism ; *Bifidobacterium/metabolism/drug effects/genetics ; Caco-2 Cells ; *Intestines/drug effects/microbiology ; *Drugs, Chinese Herbal/toxicity/chemistry ; *Euphorbia/chemistry/toxicity ; RAW 264.7 Cells ; Male ; Feces/microbiology/chemistry ; Intestinal Mucosa/metabolism/drug effects ; }, abstract = {To explore the mechanism by which vinegar-processed Euphorbiae Pekinensis Radix regulates gut microbiota and reduces intestinal toxicity, this study aimed to identify key microbial communities related to vinegar-induced detoxification and verify their functions. Using a derivatization method, the study measured the content of short-chain fatty acids(SCFAs) in feces before and after vinegar-processing of Euphorbiae Pekinensis Radix. Combined with the results of previous gut microbiota sequencing, correlation analysis was used to identify key microbial communities related to SCFAs content. Through single-bacterium transplantation experiments, the role of key microbial communities in regulating SCFAs metabolism and alleviating the intestinal toxicity of Euphorbiae Pekinensis Radix was clarified. Fecal extracts were then added to a co-culture system of Caco-2 and RAW264.7 cells, and toxicity differences were evaluated using intestinal tight junction proteins and inflammatory factors as indicators. Additionally, the application of a SCFAs receptor blocker helped confirm the role of SCFAs in reducing intestinal toxicity during vinegar-processing of Euphorbiae Pekinensis Radix. The results of this study indicated that vinegar-processing of Euphorbiae Pekinensis Radix improved the decline in SCFAs content caused by the raw material. Correlation analysis revealed that Bifidobacterium was positively correlated with the levels of acetic acid, propionic acid, isobutyric acid, n-butyric acid, isovaleric acid, and n-valeric acid. RESULTS:: from single-bacterium transplantation experiments demonstrated that Bifidobacterium could mitigate the reduction in SCFAs content induced by raw Euphorbiae Pekinensis Radix, enhance the expression of tight junction proteins, and reduce intestinal inflammation. Similarly, cell experiment results confirmed that fecal extracts from Bifidobacterium-transplanted mice alleviated inflammation and increased the expression of tight junction proteins in intestinal epithelial cells. The use of the free fatty acid receptor-2 inhibitor GLPG0974 verified that this improvement effect was related to the SCFAs pathway. This study demonstrates that Bifidobacterium is the key microbial community responsible for reducing intestinal toxicity in vinegar-processed Euphorbiae Pekinensis Radix. Vinegar-processing increases the abundance of Bifidobacterium, elevates the intestinal SCFAs content, inhibits intestinal inflammation, and enhances the expression of tight junction proteins, thereby improving the intestinal toxicity of Euphorbiae Pekinensis Radix.}, }
@article {pmid39804518, year = {2025}, author = {Claytor, JD and Lin, DL and Magnaye, KM and Guerrero, YS and Langelier, CR and Lynch, SV and El-Nachef, N}, title = {Effect of Fecal Microbiota Transplant on Antibiotic Resistance Genes Among Patients with Chronic Pouchitis.}, journal = {Digestive diseases and sciences}, volume = {70}, number = {3}, pages = {982-990}, pmid = {39804518}, issn = {1573-2568}, mesh = {Humans ; *Pouchitis/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Adult ; Middle Aged ; Chronic Disease ; Anti-Bacterial Agents/therapeutic use ; *Gastrointestinal Microbiome ; Colitis, Ulcerative/surgery ; Feces/microbiology ; *Drug Resistance, Microbial/genetics ; }, abstract = {BACKGROUND: Pouchitis is common among patients with ulcerative colitis (UC) who have had colectomy with ileal pouch-anal anastomosis. Antibiotics are first-line therapy for pouch inflammation, increasing the potential for gut colonization with multi-drug resistant organisms (MDRO). Fecal microbial transplant (FMT) is being studied in the treatment of pouchitis and in the eradication of MDRO. Prior work using aerobic antibiotic culture disks suggests that some patients with chronic pouchitis may regain fluoroquinolone sensitivity after FMT. However, gut MDRO include anaerobic, fastidious organisms that are difficult to culture using traditional methods.<br><br>AIM: We aimed to assess whether FMT reduced the abundance of antibiotic resistance genes (ARG) or affected resistome diversity, evenness, or richness in patients with chronic pouchitis.<br><br>METHODS: We collected clinical characteristics regarding infections and antibiotic exposures for 18 patients who had previously been enrolled in an observational study investigating FMT as a treatment for pouchitis. Twenty-six pre- and post-FMT stool samples were analyzed using FLASH (Finding Low Abundance Sequences by Hybridization), a CRISPR/Cas9-based shotgun metagenomic sequence enrichment technique that detects acquired and chromosomal bacterial ARGs. Wilcoxon rank sum tests were used to assess differences in clinical characteristics, ARG counts, resistome diversity and ARG richness, pre- and post-FMT.<br><br>RESULTS: All 13 of the patients with sufficient stool samples for analysis had recently received antibiotics for pouchitis prior to a single endoscopic FMT. Fecal microbiomes of all patients had evidence of multi-drug resistance genes and ESBL resistance genes at baseline; 62% encoded fluoroquinolone resistance genes. A numerical decrease in overall ARG counts was noted post-FMT, but no statistically significant differences were noted (P&#x2009;=&#x2009;0.19). Richness and diversity were not significantly altered. Three patients developed infections during the 5-year follow-up period, none of which were associated with MDRO.<br><br>CONCLUSION: Antibiotic resistance genes are prevalent among antibiotic-exposed patients with chronic pouchitis. FMT led to a numerical decrease, but no statistically significant change in ARG, nor were there significant changes in the diversity, richness, or evenness of ARGs. Further investigations to improve FMT engraftment and to optimize FMT delivery in patients with inflammatory pouch disorders are warranted.}, }
@article {pmid39801363, year = {2025}, author = {Chevalier, C and Tournier, BB and Marizzoni, M and Park, R and Paquis, A and Ceyzériat, K and Badina, AM and Lathuiliere, A and Saleri, S and Cillis, F and Cattaneo, A and Millet, P and Frisoni, GB}, title = {Fecal Microbiota Transplantation (FMT) From a Human at Low Risk for Alzheimer's Disease Improves Short-Term Recognition Memory and Increases Neuroinflammation in a 3xTg AD Mouse Model.}, journal = {Genes, brain, and behavior}, volume = {24}, number = {1}, pages = {e70012}, pmid = {39801363}, issn = {1601-183X}, support = {1216//Velux Stiftung/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; *Alzheimer Disease/therapy/microbiology ; Animals ; Humans ; Female ; Mice ; Gastrointestinal Microbiome ; Aged ; Aged, 80 and over ; *Memory, Short-Term/physiology ; Disease Models, Animal ; Mice, Transgenic ; Recognition, Psychology ; Neuroinflammatory Diseases ; Young Adult ; }, abstract = {Human microbiota-associated murine models, using fecal microbiota transplantation (FMT) from human donors, help explore the microbiome's role in diseases like Alzheimer's disease (AD). This study examines how gut bacteria from donors with protective factors against AD influence behavior and brain pathology in an AD mouse model. Female 3xTgAD mice received weekly FMT for 2 months from (i) an 80-year-old AD patient (AD-FMT), (ii) a cognitively healthy 73-year-old with the protective APOEe2 allele (APOEe2-FMT), (iii) a 22-year-old healthy donor (Young-FMT), and (iv) untreated mice (Mice-FMT). Behavioral assessments included novel object recognition (NOR), Y-maze, open-field, and elevated plus maze tests; brain pathology (amyloid and tau), neuroinflammation (in situ autoradiography of the 18 kDa translocator protein in the hippocampus); and gut microbiota were analyzed. APOEe2-FMT improved short-term memory in the NOR test compared to AD-FMT, without significant changes in other behavioral tests. This was associated with increased neuroinflammation in the hippocampus, but no effect was detected on brain amyloidosis and tauopathy. Specific genera, such as Parabacteroides and Prevotellaceae_UGC001, were enriched in the APOEe2-FMT group and associated with neuroinflammation, while genera like Desulfovibrio were reduced and linked to decreased neuroinflammation. Gut microbiota from a donor with a protective factor against AD improved short-term memory and induced neuroinflammation in regions strategic to AD. The association of several genera with neuroinflammation in the APOEe2-FMT group suggests a collegial effect of the transplanted microbiome rather than a single-microbe driver effect. These data support an association between gut bacteria, glial cell activation, and cognitive function in AD.}, }
@article {pmid39800714, year = {2025}, author = {Sall, I and Foxall, R and Felth, L and Maret, S and Rosa, Z and Gaur, A and Calawa, J and Pavlik, N and Whistler, JL and Whistler, CA}, title = {Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446423}, pmid = {39800714}, issn = {1949-0984}, support = {F31 DA056222/DA/NIDA NIH HHS/United States ; P20 GM103506/GM/NIGMS NIH HHS/United States ; R15 DA058187/DA/NIDA NIH HHS/United States ; R21 DA049565/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dysbiosis/microbiology/chemically induced ; *Morphine/administration &amp; dosage/pharmacology ; Mice ; *Drug Tolerance ; *Butyrates/metabolism ; Male ; Fecal Microbiota Transplantation ; *Analgesics, Opioid/administration &amp; dosage/pharmacology ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; Disease Models, Animal ; Bacteria/classification/metabolism/genetics/isolation &amp; purification ; }, abstract = {The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.}, }
@article {pmid39800223, year = {2025}, author = {Lista, S and Munafò, A and Caraci, F and Imbimbo, C and Emanuele, E and Minoretti, P and Pinto-Fraga, J and Merino-País, M and Crespo-Escobar, P and López-Ortiz, S and Monteleone, G and Imbimbo, BP and Santos-Lozano, A}, title = {Gut microbiota in Alzheimer's disease: Understanding molecular pathways and potential therapeutic perspectives.}, journal = {Ageing research reviews}, volume = {104}, number = {}, pages = {102659}, doi = {10.1016/j.arr.2025.102659}, pmid = {39800223}, issn = {1872-9649}, mesh = {Humans ; *Alzheimer Disease/microbiology/therapy/metabolism/immunology ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; Animals ; Probiotics/therapeutic use ; Brain/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.}, }
@article {pmid39800192, year = {2025}, author = {Bajaj, JS and Fagan, A and Gavis, EA and Sterling, RK and Gallagher, ML and Lee, H and Matherly, SC and Siddiqui, MS and Bartels, A and Mousel, T and Davis, BC and Puri, P and Fuchs, M and Moutsoglou, DM and Thacker, LR and Sikaroodi, M and Gillevet, PM and Khoruts, A}, title = {Microbiota transplant for hepatic encephalopathy in cirrhosis: The THEMATIC trial.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2024.12.047}, pmid = {39800192}, issn = {1600-0641}, abstract = {BACKGROUND &amp; AIMS: Preventing hepatic encephalopathy (HE) recurrence in cirrhosis, which is associated with an altered gut-liver-brain axis, is an unmet need. Benefits of fecal microbiota transplantation (FMT) have been shown in phase I studies, but route and dose-related questions remain.<br><br>METHODS: We performed a phase II randomized, placebo-controlled, double-blind, clinical trial of capsule and enema FMT in patients with cirrhosis and HE on lactulose and rifaximin. Participants were randomized into four groups (3 active doses; 2 active and 1 placebo dose; 1 active and 2 placebo doses; 3 placebo doses). Each patient received two capsules and one enema (either placebo or FMT) and were followed for 6 months. The primary outcome was FMT-related (serious) adverse events ([s]AEs)/AEs using intention-to-treat analysis. Secondary outcomes were HE recurrence, all-cause hospitalizations, death, donor engraftment, and quality-of-life. FMT was from a vegan or omnivorous donor.<br><br>RESULTS: We enrolled 60 patients (15/group) with similar baseline characteristics. FMT was safe without any FMT-related SAEs/AEs. Overall SAEs (p&#xa0;= 0.96) or death (p&#xa0;= 1.0) were similar. There were significant differences in HE recurrence between groups (p&#xa0;= 0.035, Cramer's V&#xa0;= 0.39). On post hoc analysis, recurrence was highest in the all-placebo vs. any FMT group (40% vs. 9%; odds ratio 0.15, 95% CI 0.04-0.64). Within the FMT groups, HE recurrence rates were similar regardless of route, doses, or donor type. Quality of life improved in FMT-recipient groups. Engraftment was highest in those with high pre-FMT Lachnospiraceae and lower in those whose HE recurred.<br><br>CONCLUSIONS: In patients with cirrhosis and HE on maximal therapy, FMT regardless of dose, route, or donor was safe without any FMT-related AEs. On post hoc analysis, HE recurrence was highest in the placebo-only group and linked with lower baseline Lachnospiraceae and reduced donor engraftment.<br><br>IMPACT AND IMPLICATIONS: Patients with hepatic encephalopathy (HE) already on maximal therapy could have recurrences, which worsen prognosis and are not prioritized for liver transplant. In this phase II, double-blind, randomized, placebo-controlled trial in patients with cirrhosis and prior overt HE, we found that fecal microbiota transplant (FMT) was safe and well tolerated regardless of route of delivery (oral or enema), number of doses (1 through 3), or donor type (vegan or omnivorous). HE recurrence, which was a key secondary endpoint, was different between groups and, on post hoc analysis, lowest in groups that received any FMT. Donor engraftment was higher in those with higher relative abundance of Lachnospiraceae, which was associated with lower HE recurrence.}, }
@article {pmid39798925, year = {2025}, author = {Aleksandrova, RR and Nieuwenhuis, LM and Karmi, N and Zhang, S and Swarte, JC and Björk, JR and Gacesa, R and Blokzijl, H and Connelly, MA and Weersma, RK and Lisman, T and Festen, EAM and de Meijer, VE and , }, title = {Gut microbiome dysbiosis is not associated with portal vein thrombosis in patients with end-stage liver disease: a cross-sectional study.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {23}, number = {4}, pages = {1407-1415}, doi = {10.1016/j.jtha.2024.12.036}, pmid = {39798925}, issn = {1538-7836}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Dysbiosis ; *Portal Vein ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; *Venous Thrombosis/microbiology/blood/diagnosis ; Methylamines/blood ; Feces/microbiology ; *End Stage Liver Disease/microbiology/complications/diagnosis/blood ; Case-Control Studies ; Aged ; Adult ; *Bacteria/classification/metabolism/genetics ; }, abstract = {BACKGROUND: Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in patients with ESLD is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a proinflammatory gut microbiome and elevated trimethylamine N-oxide (TMAO), a driver of thrombosis, may contribute to PVT development.<br><br>OBJECTIVES: We investigated whether gut microbiome diversity, bacterial species, metabolic pathways, and TMAO levels are associated with PVT in patients with ESLD.<br><br>METHODS: Fecal samples, plasma samples, and data from patients with ESLD and healthy controls were collected through the TransplantLines Biobank and Cohort Study. PVT was defined as a thrombus in the portal vein within a year prior to or after fecal sample collection. Fecal samples were analyzed using Shotgun Metagenomic Sequencing, and TMAO levels were measured in plasma using a Vantera Clinical Analyzer.<br><br>RESULTS: One hundred two patients with ESLD, of which 23 with PVT, and 246 healthy controls were included. No significant difference in gut microbiome diversity was found between patients with PVT and without PVT (P&#xa0;= .18). Both ESLD groups had significantly lower alpha diversity than controls. Bacteroides fragilis and 3 Clostridiales species were increased in patients with PVT compared with without PVT. TMAO levels between the 3 groups were not significantly different.<br><br>CONCLUSION: We observed profound differences in gut microbiota between patients with ESLD and controls, but minimal differences between patients with ESLD with or without PVT. In our cohort, a gut-derived proinflammatory state was not associated with presence of PVT in patients with ESLD.}, }
@article {pmid39797102, year = {2024}, author = {Díez-Madueño, K and de la Cueva Dobao, P and Torres-Rojas, I and Fernández-Gosende, M and Hidalgo-Cantabrana, C and Coto-Segura, P}, title = {Gut Dysbiosis and Adult Atopic Dermatitis: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {1}, pages = {}, pmid = {39797102}, issn = {2077-0383}, abstract = {Background/Objectives: Research on the relationship between gut microbiota (GM) and atopic dermatitis (AD) has seen a growing interest in recent years. The aim of this systematic review was to determine whether differences exist between the GM of adults with AD and that of healthy adults (gut dysbiosis). Methods: We conducted a systematic review based on the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed using PubMed, EMBASE, and Web of Science. Observational and interventional studies were analyzed. Results: Although the studies showed heterogeneous results, some distinguishing characteristics were found in the intestinal microbial composition of adults with dermatitis. Even though no significant differences in diversity were found between healthy and affected adults, certain microorganisms, such as Bacteroidales, Enterobacteriaceae, and Clostridium (perfringens), were more characteristic of the fecal microbiota in adults with AD. Healthy individuals exhibited lower abundances of aerobic bacteria and higher abundances of short-chain fatty acid-producing species and polyamines. Clinical trials showed that the consumption of probiotics (Bifidobacterium and/or Lactobacillus), fecal microbiota transplants, and balneotherapy modified the fecal microbiota composition of participants and were associated with significant improvements in disease management. Conclusions: In anticipation of forthcoming clinical trials, it is essential to conduct meta-analyses that comprehensively evaluate the effectiveness and safety of interventions designed to modify intestinal flora in the context of AD. Preliminary evidence suggests that certain interventions may enhance adult AD management.}, }
@article {pmid39796717, year = {2024}, author = {Kumari, S and Srilatha, M and Nagaraju, GP}, title = {Effect of Gut Dysbiosis on Onset of GI Cancers.}, journal = {Cancers}, volume = {17}, number = {1}, pages = {}, pmid = {39796717}, issn = {2072-6694}, abstract = {Dysbiosis in the gut microbiota plays a significant role in GI cancer development by influencing immune function and disrupting metabolic functions. Dysbiosis can drive carcinogenesis through pathways like immune dysregulation and the release of carcinogenic metabolites, and altered metabolism, genetic instability, and pro-inflammatory signalling, contributing to GI cancer initiation and progression. Helicobacter pylori infection and genotoxins released from dysbiosis, lifestyle and dietary habits are other factors that contribute to GI cancer development. Emerging diagnostic and therapeutic approaches show promise in colorectal cancer treatment, including the multitarget faecal immunochemical test (mtFIT), standard FIT, and faecal microbiota transplantation (FMT) combined with PD-1 inhibitors. We used search engine databases like PubMed, Scopus, and Web of Science. This review discusses the role of dysbiosis in GI cancer onset and explores strategies such as FMT, probiotics, and prebiotics to enhance the immune response and improve cancer therapy outcomes.}, }
@article {pmid39796536, year = {2024}, author = {Cuffaro, F and Lamminpää, I and Niccolai, E and Amedei, A}, title = {Nutritional and Microbiota-Based Approaches in Amyotrophic Lateral Sclerosis: From Prevention to Treatment.}, journal = {Nutrients}, volume = {17}, number = {1}, pages = {}, pmid = {39796536}, issn = {2072-6643}, support = {PNRR-MAD-2022-12375798//Ministero della Salute/ ; PE0000006//Ministry of University and Research (MUR)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/prevention &amp; control/therapy/microbiology/diet therapy ; Humans ; *Gastrointestinal Microbiome/physiology ; Probiotics ; Dysbiosis ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Oxidative Stress ; Fatty Acids, Omega-3/administration &amp; dosage ; }, abstract = {Metabolic alterations, including hypermetabolism, lipid imbalances, and glucose dysregulation, are pivotal contributors to the onset and progression of Amyotrophic Lateral Sclerosis (ALS). These changes exacerbate systemic energy deficits, heighten oxidative stress, and fuel neuroinflammation. Simultaneously, gastrointestinal dysfunction and gut microbiota (GM) dysbiosis intensify disease pathology by driving immune dysregulation, compromising the intestinal barrier, and altering gut-brain axis (GBA) signaling, and lastly advancing neurodegeneration. Therapeutic and preventive strategies focused on nutrition offer promising opportunities to address these interconnected pathophysiological mechanisms. Diets enriched with antioxidants, omega-3 fatty acids, and anti-inflammatory compounds-such as the Mediterranean diet-have shown potential in reducing oxidative stress and systemic inflammation. Additionally, microbiota-targeted approaches, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, are emerging as innovative tools to restore microbial balance, strengthen gut integrity, and optimize GBA function. This review highlights the critical need for personalized strategies integrating immunonutrition and microbiota modulation to slow ALS progression, improve quality of life, and develop preventive measures for neurodegenerative and neuroinflammatory diseases. Future research should prioritize comprehensive dietary and microbiota-based interventions to uncover their therapeutic potential and establish evidence-based guidelines for managing ALS and related disorders.}, }
@article {pmid39796390, year = {2025}, author = {Yu, R and Zhang, H and Chen, R and Lin, Y and Xu, J and Fang, Z and Ru, Y and Fan, C and Wu, G}, title = {Fecal Microbiota Transplantation from Methionine-Restricted Diet Mouse Donors Improves Alzheimer's Learning and Memory Abilities Through Short-Chain Fatty Acids.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39796390}, issn = {2304-8158}, support = {LQ22H260002//Natural Science Foundation of Zhejiang Province/ ; 82103836//National Natural Science Foundation of China/ ; }, abstract = {Alzheimer's disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored. In this study, APP/PS1 double transgenic AD mice were used and an FMT experiment was conducted. 16S rRNA gene sequencing, targeted metabolomics, and microbial metabolite short-chain fatty acids (SCFAs) of feces samples were analyzed. The results showed that MR reversed the reduction in SCFAs induced by AD, and further activated the free fatty acid receptors, FFAR2 and FFAR3, as well as the transport protein MCT1, thereby signaling to the brain to mitigate inflammation and enhance the learning and memory capabilities. Furthermore, the FMT experiment from methionine-restricted diet mouse donors showed that mice receiving FMT ameliorated Alzheimer's learning and memory ability through SCFAs. This study offers novel non-pharmaceutical intervention strategies for AD prevention.}, }
@article {pmid39795549, year = {2024}, author = {Tsuji, K and Uchida, N and Nakanoh, H and Fukushima, K and Haraguchi, S and Kitamura, S and Wada, J}, title = {The Gut-Kidney Axis in Chronic Kidney Diseases.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {39795549}, issn = {2075-4418}, support = {24K11411//the Japanese Society for the Promotion of Science (JSPS)/Grant-in-Aid for Young Scientists/ ; }, abstract = {The gut-kidney axis represents the complex interactions between the gut microbiota and kidney, which significantly impact the progression of chronic kidney disease (CKD) and overall patient health. In CKD patients, imbalances in the gut microbiota promote the production of uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which impair renal function and contribute to systemic inflammation. Mechanisms like endotoxemia, immune activation and oxidative stress worsen renal damage by activating pro-inflammatory and oxidative pathways. Insights into these mechanisms highlight the impact of gut-derived metabolites, bacterial translocation, and immune response changes on kidney health, suggesting new potential approaches for CKD treatment. Clinical applications, such as dietary interventions, prebiotics, probiotics and fecal microbiota transplantation, are promising in adjusting the gut microbiota to alleviate CKD symptoms and slow disease progression. Current research highlights the clinical relevance of the gut-kidney axis, but further study is essential to clarify these mechanisms' diagnostic biomarkers and optimize therapeutic interventions. This review emphasizes the importance of an integrated approach to CKD management, focusing on the gut microbiota as a therapeutic target to limit kidney injury.}, }
@article {pmid39792405, year = {2024}, author = {Guo, Z and He, M and Shao, L and Li, Y and Xiang, X and Wang, Q}, title = {The role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease.}, journal = {Journal of cancer research and therapeutics}, volume = {20}, number = {7}, pages = {1964-1973}, doi = {10.4103/jcrt.jcrt_33_24}, pmid = {39792405}, issn = {1998-4138}, mesh = {Humans ; *Graft vs Host Disease/therapy/etiology/microbiology ; *Fecal Microbiota Transplantation/methods ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; *Gastrointestinal Microbiome ; Transplantation, Homologous/methods ; Acute Disease ; Treatment Outcome ; }, abstract = {Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most important methods for treating a wide range of hematologic malignancies and bone marrow failure diseases. However, graft-versus-host disease (GVHD), a major complication associated with this method, can seriously affect the survival and quality of life of patients. Acute GVHD (aGVHD) occurs within 100 days after transplantation, and gastrointestinal aGVHD (GI-aGVHD) is one of the leading causes of nonrecurrent death after allo-HSCT. In recent years, fecal microbiota transplantation (FMT) has been attempted as an emerging treatment method for various diseases, including aGVHD after HSCT. Studies have shown encouraging preliminary clinical results after the application of FMT in aGVHD, particularly steroid-resistant aGVHD. Additionally, several studies have demonstrated that the gut microbiota plays an important immunomodulatory role in the pathogenesis of GVHD. Consensus guidelines recommend FMT as a secondary option for the treatment of aGVHD. This article aims to review FMT treatment for GI-aGVHD after allo-HSCT.}, }
@article {pmid39791180, year = {2025}, author = {Shakya, R and Sivakumar, PM and Prabhakar, PK}, title = {Gut Microbiota and Diabetes: Pioneering New Treatment Frontiers.}, journal = {Endocrine, metabolic &amp; immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303342579241119155225}, pmid = {39791180}, issn = {2212-3873}, abstract = {Diabetes Mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and poses significant global health challenges. Conventional treatments, such as insulin therapy and lifestyle modifications, have shown limited efficacy in addressing the multifactorial nature of DM. Emerging evidence suggests that gut microbiota, a diverse community of microorganisms critical for metabolism and immune function, plays a pivotal role in metabolic health. Dysbiosis, an imbalance in gut microbiota composition, has been linked to insulin resistance, obesity, and DM. Gut microbiota influences glucose metabolism through mechanisms, including short-chain fatty acid production, gut permeability regulation, and immune system interactions, indicating a bidirectional relationship between microbial health and metabolism. Clinical and experimental studies demonstrate that modulating gut microbiota through dietary interventions (prebiotics, probiotics, synbiotics) improves glycemic control and insulin sensitivity in DM patients. Fecal Microbiota Transplantation (FMT) has also shown promise in restoring healthy gut microbiota and alleviating DM-related metabolic disturbances. However, challenges remain, including the need for personalized treatments due to individual microbiota variability and the unknown long-term effects of these interventions. Future research should focus on elucidating the mechanisms by which gut microbiota influences metabolism and refining personalized approaches to enhance DM management.}, }
@article {pmid39791141, year = {2025}, author = {Li, X and Sun, B and Qin, Y and Yue, F and Lü, X}, title = {Amelioration of Obesity-Related Disorders in High-Fat Diet-Fed C57BL/6 Mice Following Fecal Microbiota Transplantation From DL-Norvaline-Dosed Mice.}, journal = {Molecular nutrition &amp; food research}, volume = {69}, number = {3}, pages = {e202400577}, doi = {10.1002/mnfr.202400577}, pmid = {39791141}, issn = {1613-4133}, support = {2023-ZDLNY-35//Shaanxi Province Science and Technology Plan Project/ ; 2022A02006//Major Scientific and Technological Special Project of Xinjiang Uygur Autonomous Region/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Valine/analogs &amp; derivatives/pharmacology/administration &amp; dosage ; *Obesity/therapy/microbiology/etiology ; *Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; *Diet, High-Fat/adverse effects ; Male ; Mice ; }, abstract = {Fecal microbiota transplantation (FMT) could significantly alter the recipient's gut bacteria composition and attenuate obesity and obesity-related metabolic syndromes. DL-norvaline is a nonproteinogenic amino acid and possesses anti-obesity potential. However, the specific mechanisms by which gut microbiota might mediate beneficial effects of DL-norvaline have not been completely elucidated. In this study, DL-norvaline-mediated FMT upregulated the beneficial bacteria (Clostridia_UCG_014, Christensenellales, Bacilli, Ileibacterium, Dubosiella, Lactobacillus, Muribaculaceae, and Bacteroidaceae) and downregulated the harmful bacteria (Tuzzerella and Marinifilaceae), further intestinal inflammation, oxidative stress, and intestinal barrier were alleviated as well as short chain fatty acids levels were increased, thus alleviating glucose and insulin metabolism, improving biochemical indexes and energy metabolism and decreasing body weight gain and tissue weight. However, heat-inactivated FMT did not demonstrate any of those improvements in obese mice. Notably, both DL-norvaline-mediated FMT and heat-inactivated FMT increased Bacteroidaceae and Muribaculaceae, this being a signature of alterations to the gut microbiota marker caused by DL-norvaline. Therefore, the beneficial effects of DL-norvaline were transmissible via FMT. This study highlighted the pivotal involvement of the gut microbiota in the development of obesity and provided a novel insight into the underlying mechanisms of FMT, thereby potentially enhancing the efficacy and refinement of FMT utilization.}, }
@article {pmid39791120, year = {2024}, author = {Huang, H and Yang, Y and Wang, X and Wen, B and Yang, X and Zhong, W and Wang, Q and He, F and Li, J}, title = {Gut virome dysbiosis impairs antitumor immunity and reduces 5-fluorouracil treatment efficacy for colorectal cancer.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1501981}, pmid = {39791120}, issn = {2234-943X}, abstract = {INTRODUCTION: Despite the established influence of gut bacteria, the role of the gut virome in modulating colorectal cancer (CRC) patient chemotherapy response remains poorly understood. In this study, we investigated the impact of antiviral (AV) drug-induced gut virome dysbiosis on the efficacy of 5-FU in CRC treatment.<br><br>METHODS: Using a subcutaneous CRC mouse model, we assessed tumor growth and immune responses following AV treatment, fecal microbiota transplantation (FMT), and 5-FU administration.<br><br>RESULTS: AV therapy reduced the abundance of gut DNA and RNA viruses, leading to accelerated tumor growth, shortened survival, and diminished chemotherapy efficacy. FMT restored the gut virome, improving tumor suppression and extending the survival of 5-FU-treated mice. Metagenomic sequencing revealed significant changes in virome composition, AV treatment expanded Kahnovirus, Petivirales, and Enterogokushovirus, whereas FMT enriched Peduovirus STYP1, Mahlunavirus rarus, and Jouyvirus ev207. AV treatment reduced the number of dendritic cells and CD8+ T cells in peripheral blood and tumor tissues, impairing antitumor immunity, FMT reversed these deficiencies. To further investigate the underlying mechanisms, we examined the TLR3-IRF3-IFN-&#x3b2; pathway, essential for recognizing viral RNA and triggering immune responses. AV treatment downregulated this pathway, impairing immune cell recruitment and reducing chemotherapy efficacy, while activation of TLR3 with Poly(I:C) restored pathway function and enhanced the effectiveness of 5-FU.<br><br>DISCUSSION: These findings suggest the importance of maintaining gut virome integrity or activating TLR3 as adjunct strategies to enhance chemotherapy outcomes in CRC patients.}, }
@article {pmid39791110, year = {2025}, author = {Høyer, KL and Dahl Baunwall, SM and Kornum, DS and Klinge, MW and Drewes, AM and Yderstræde, KB and Thingholm, LB and Mortensen, MS and Mikkelsen, S and Erikstrup, C and Hvas, CL and Krogh, K}, title = {Faecal microbiota transplantation for patients with diabetes type 1 and severe gastrointestinal neuropathy (FADIGAS): a randomised, double-blinded, placebo-controlled trial.}, journal = {EClinicalMedicine}, volume = {79}, number = {}, pages = {103000}, pmid = {39791110}, issn = {2589-5370}, abstract = {BACKGROUND: Diabetic gastroenteropathy is associated with nausea, vomiting, bloating, pain, constipation, and diarrhoea. Current therapies are scarce. We tested faecal microbiota transplantation (FMT) for patients with type 1 diabetes and gastroenteropathy.<br><br>METHODS: In a randomised, double-blinded, placebo-controlled pilot trial, adults with type 1 diabetes and moderate-to-severe gastrointestinal symptoms were randomised (1:1) to encapsulated FMT or placebo. Each patient received around 25 capsules containing 50&#xa0;g of faeces, administered in a single dose. The placebo capsules contained glycerol, saline and food colouring. All patients received FMT as a second intervention. The primary endpoint was number of adverse events of severity grade 2 or more assessed by the Common Terminology Criteria for Adverse Events during the week following the first intervention. Secondary endpoints included gastrointestinal symptoms and quality of life assessed four weeks after treatment. Public trial registration, ClinicalTrials.govNCT04749030.<br><br>FINDINGS: We randomised 20 patients to FMT or placebo. Following this intervention, 26 adverse events of grade 2 or more occurred. Four patients in the FMT group reported seven adverse events, and five patients in the placebo group reported 19, with no differences between the groups. The most frequent adverse events were diarrhoea, bloating, and abdominal pain. No serious adverse events were related to the treatment. Patients who received FMT reduced their median Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome score from 58 (IQR 54-65) to 35 (32-48), whereas patients receiving placebo reduced their score from 64 (55-70) to 56 (50-77) (p&#xa0;=&#xa0;0.01). The Irritable Bowel Syndrome Impact Scale score improved from 108 (101-123) to 140 (124-161) with FMT and 77 (53-129) to 92 (54-142) with placebo (p&#xa0;=&#xa0;0.02). The Patient Assessment of Gastrointestinal Symptom Severity Index declined from a median of 42 (28-47) to 25 (14-31) after FMT and 47 (31-69) to 41 (36-64) after placebo (p&#xa0;=&#xa0;0.03).<br><br>INTERPRETATION: FMT was safe and improved clinical outcomes for patients with type 1 diabetes suffering from bowel symptoms.<br><br>FUNDING: Steno Collaborative Grant.}, }
@article {pmid39788762, year = {2025}, author = {Augustijn, QJJ and Grefhorst, A and de Groen, P and Wortelboer, K and Seegers, JFM and Gül, IS and Suenaert, P and Verheij, J and de Vos, WM and Herrema, H and Nieuwdorp, M and Holleboom, AG}, title = {Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e088290}, pmid = {39788762}, issn = {2044-6055}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Capsules ; Double-Blind Method ; *Fatty Liver/metabolism/physiopathology/therapy ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Freeze Drying ; *Gastrointestinal Microbiome ; *Randomized Controlled Trials as Topic ; Placebos ; *Bacteria ; }, abstract = {BACKGROUND: The spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, affecting 30% of the world's population, with a significant risk of hepatic and cardiometabolic complications. Different stages of MASLD are accompanied by distinct gut microbial profiles, and several microbial components have been implicated in MASLD pathophysiology. Indeed, earlier studies demonstrated that hepatic necroinflammation was reduced in individuals with MASLD after allogenic faecal microbiota transplantation (FMT) from healthy donors on a vegan diet. Here, we further investigate the therapeutic potential of gut microbiome modulation using a syntrophic combination of next-generation beneficial bacteria with FMT in individuals with advanced MASLD.<br><br>METHODS AND ANALYSIS: This trial is a randomised, double-blind, placebo-controlled study investigating the therapeutic potential of lyophilised faecal microbiota capsules (LFMCs) in individuals with metabolic dysfunction-associated steatohepatitis. In this study, 48 participants will be randomised 1:1 to receive either healthy vegan donor LFMCs or placebo for 24 weeks. In addition, all participants will be supplemented with a set of next-generation beneficial bacteria, including Anaerobutyricum soehngenii, pasteurised Akkermansia muciniphila and Bifidobacterium animalis subsp. lactis, as well as fructo-oligosaccharides. A liver biopsy will be performed at baseline and at the end of the trial. In addition, participants will be assessed through MRI, FibroScan, blood tests, faecal samples and continuous glucose monitoring. The first participant was enrolled on 25 April 2023.<br><br>ETHICS AND DISSEMINATION: Ethical approval was obtained from the Medical Ethics Committee of the University Medical Centre of Amsterdam. The results of this study will be disseminated through peer-reviewed journals.<br><br>TRIAL REGISTRATION NUMBER: The trial is registered on clinicaltrials.gov (NCT05821010).}, }
@article {pmid39788096, year = {2025}, author = {Wang, W and Pi, Z and Yu, Y and Zhang, F}, title = {The butterfly effect of the strain richness influences the efficacy of microbiota transplantation.}, journal = {Cell host &amp; microbe}, volume = {33}, number = {1}, pages = {3-5}, doi = {10.1016/j.chom.2024.12.010}, pmid = {39788096}, issn = {1934-6069}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Animals ; Feces/microbiology ; Bacteria/classification ; }, abstract = {Strain-level variation in the gut microbiome modulates its impact on host health. Recently in Nature, Chen-Liaw et al. propose that strain richness is a crucial element in the gut ecosystem, thus influencing efficacy of fecal microbiota transplantation, and provide a theoretical foundation for optimizing microbiota-based treatments and developing microbiota medicine.}, }
@article {pmid39787138, year = {2025}, author = {Luo, Y and Zhou, S and Zhang, X and Lin, Y and Liu, J and Cheng, W and Zeng, Y}, title = {The role of the microbiota and metabolites in the treatment of pulmonary fibrosis with UC-MSCs: Integrating fecal metabolomics and 16S rDNA analysis.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0313989}, pmid = {39787138}, issn = {1932-6203}, mesh = {Animals ; Mice ; *Pulmonary Fibrosis/therapy/metabolism/pathology/microbiology ; *Metabolomics/methods ; *Feces/microbiology ; *RNA, Ribosomal, 16S/genetics ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/metabolism ; Gastrointestinal Microbiome ; Male ; DNA, Ribosomal/genetics ; Mice, Inbred C57BL ; Disease Models, Animal ; Lung/pathology/metabolism/microbiology ; Bleomycin ; Microbiota ; Cytokines/metabolism ; }, abstract = {INTRODUCTION: Pulmonary fibrosis (PF) is a chronic and irreversible interstitial lung disease characterized by a lack of effective therapies. Mesenchymal stem cells (MSCs) have garnered significant interest in the realm of lung regeneration due to their abundant availability, ease of isolation, and capacity for expansion. The objective of our study was to investigate the potential therapeutic role of umbilical cord-derived MSCs (UC-MSCs) in the management of PF, with a focus on the alterations in the gut microbiota and its metabolites during the use of UC-MSCs for the treatment of pulmonary fibrosis, as well as the possible mechanisms involved.<br><br>METHODS: Bleomycin injection was utilized to establish a mouse model of lung fibrosis, followed by the application of 16S rDNA sequencing and LC-MS/MS metabolomics to explore the underlying mechanism of UC-MSC treatment for lung fibrosis. Seventy-five mice were allocated into five groups, namely Control, Model, and low/medium/high dose of UC-MSCs groups, and survival metrics, lung morphology, and the levels of the inflammatory cytokines TNF-&#x3b1;, IL-1&#x3b2;, IL-6, and TGF-&#x3b2;1 were subsequently evaluated. Fecal samples from six mice in each of the Control group, Model group, and UC-MSCs-M groups were collected randomly for 16S rDNA sequencing to analyze the gut microbiota and nontargeted metabolomics.<br><br>RESULTS: In comparison to IPF model mice, the three treatment groups exhibited increased survival rates, restored alveolar morphology, and reduced levels of the inflammatory cytokines TNF-&#x3b1;, IL-1&#x3b2;, IL-6, and TGF-&#x3b2;1, confirming the anti-inflammatory properties of UC-MSCs in IPF treatment. The findings from the 16S rDNA assay indicate that UC-MSCs treatment effectively lower &#x3b1;-diversity induced such as Chao 1 and ACE, as well as &#x3b2;-diversity, leading to a decrease in microbiota abundance. The findings from the metabolomics analysis revealed that the metabolites exhibiting notable variances were primarily composed of Lipids and lipid-like molecules, Organoheterocyclic compounds, Organic acids and derivatives, and Benzenoids, indicating the potential of UC-MSCs to exert antifibrotic effects via these metabolic pathways.<br><br>CONCLUSION: Umbilical cord-derived mesenchymal stem cells (UC-MSCs) ameliorate bleomycin-induced pulmonary fibrosis symptoms in mice by exerting anti-inflammatory effects and mitigating pulmonary fibrosis through the modulation of gut microbiota disorders and their metabolism. These findings offer novel insights into the potential mechanisms and clinical utility of stem cell therapy for pulmonary fibrosis.}, }
@article {pmid39786379, year = {2025}, author = {Yang, Q and Zhu, Y and Jian, X and Qiu, Y and Zhu, Y and Zhao, L and He, Y and An, G and Qiu, L and Guo, J and He, N and Abudumijiti, H and Hu, C and Chen, X and Huang, S and Feng, X and Li, X and Liu, J and Xu, Y and Zhou, W}, title = {Targeting Enterobacter cloacae attenuates osteolysis by reducing ammonium in multiple myeloma.}, journal = {Blood}, volume = {145}, number = {17}, pages = {1876-1889}, doi = {10.1182/blood.2024025694}, pmid = {39786379}, issn = {1528-0020}, mesh = {*Enterobacter cloacae/metabolism/physiology ; *Multiple Myeloma/microbiology/complications/metabolism/pathology ; Animals ; Mice ; *Osteolysis/microbiology/etiology/pathology/metabolism/therapy ; Humans ; *Ammonium Compounds/metabolism/blood ; Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Female ; Male ; }, abstract = {Multiple myeloma (MM)-induced bone disease affects not only patients' quality of life but also their overall survival. Our previous work demonstrated that the gut microbiome plays a crucial role in MM progression and drug resistance. However, the role of altered gut microbiota in MM bone disease remains unclear. In this study, we show that intestinal Enterobacter cloacae is significantly enriched in patients with MM with osteolysis. Through fecal microbial transplantation and single bacterial colonization experiments in a 5TGM1 MM mouse model, we found that intestinal colonization of E cloacae promotes osteolysis by increasing circulating ammonium levels. Elevated ammonium promotes osteoclastogenesis by increasing Trap protein levels in osteoclast precursors and by acetylating and stabilizing chemokine ligand 3 protein in MM cells. Inhibition of ammonium synthesis, using E cloacae with a deleted dcd gene, along with probiotic supplementation, alleviated osteolysis in MM. Overall, our work suggests that E cloacae promotes osteolysis in MM by synthesizing ammonium. This establishes a novel mechanism and potential intervention strategy for managing MM with osteolysis.}, }
@article {pmid39780269, year = {2025}, author = {Li, X and Ding, Q and Wan, X and Wu, Q and Ye, S and Lou, Y}, title = {Fecal microbiota transplantation attenuates Alzheimer's disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation.}, journal = {Behavioral and brain functions : BBF}, volume = {21}, number = {1}, pages = {2}, pmid = {39780269}, issn = {1744-9081}, support = {Grant No. Y20220029//Health Project of the Science and Technology Department of Wenzhou/ ; 231104408302408//Industry-university Cooperative education program of Ministry of Education/ ; First Class, Category A//the Key Discipline of Zhejiang Province in Medical Technology/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Myeloid Differentiation Factor 88/metabolism ; Mice ; *Alzheimer Disease/therapy/microbiology ; *Mice, Transgenic ; *Toll-Like Receptor 4/metabolism ; *NF-kappa B/metabolism ; *Signal Transduction/physiology ; *Presenilin-1/genetics ; Amyloid beta-Protein Precursor/genetics ; Gastrointestinal Microbiome/physiology ; Inflammation/therapy/metabolism ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Alzheimer's disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to play a crucial role in the pathogenesis of AD. Additionally, disruption of the gut microbiota has been found to be associated with AD, and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach. However, the precise mechanism of FMT in the treatment of AD remains elusive. In this study, FMT was performed by transplanting fecal microbiota from healthy wild-type mice into APP/PS1 mice (APPswe, PSEN1dE9) to assess the effectiveness of FMT in mitigating AD-associated inflammation and to reveal its precise mechanism of action. The results demonstrated that FMT treatment improved cognitive function and reduced the expression levels of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway in mice, which was accompanied by the restoration of gut microbial dysbiosis. These findings suggest that FMT has the potential to ameliorate AD symptoms and delay the disease progression in APP/PS1 mice.}, }
@article {pmid39779925, year = {2025}, author = {He, X and Hu, M and Xu, Y and Xia, F and Tan, Y and Wang, Y and Xiang, H and Wu, H and Ji, T and Xu, Q and Wang, L and Huang, Z and Sun, M and Wan, Y and Cui, P and Liang, S and Pan, Y and Xiao, S and He, Y and Song, R and Yan, J and Quan, X and Wei, Y and Hong, C and Liao, W and Li, F and El-Omar, E and Chen, J and Qi, X and Gao, J and Zhou, H}, title = {The gut-brain axis underlying hepatic encephalopathy in liver cirrhosis.}, journal = {Nature medicine}, volume = {31}, number = {2}, pages = {627-638}, pmid = {39779925}, issn = {1546-170X}, support = {82372305//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {*Hepatic Encephalopathy/microbiology/metabolism/pathology/etiology ; Animals ; *Liver Cirrhosis/microbiology/complications/metabolism ; Humans ; *Gastrointestinal Microbiome/genetics/physiology ; Mice ; *Brain/metabolism/pathology ; Male ; Aromatic-L-Amino-Acid Decarboxylases/genetics/metabolism ; Liver/metabolism/pathology ; Fecal Microbiota Transplantation ; Female ; Dysbiosis/microbiology ; *Brain-Gut Axis ; Middle Aged ; Monoamine Oxidase/metabolism ; Mice, Inbred C57BL ; }, abstract = {Up to 50-70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut-brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus, increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R. gnavus showed brain phenylethylamine (PEA) accumulation, along with memory impairment, symmetrical tremors and cortex-specific neuron loss, typically found in patients with HE. This accumulation of PEA was primarily driven by decreased monoamine oxidase-B activity in both the liver and serum due to cirrhosis. Targeting PDC or PEA reversed the neurological symptoms induced by R. gnavus. Furthermore, fecal microbiota transplantation from patients with HE to germ-free cirrhotic mice replicated these symptoms and further corroborated the efficacy of targeting PDC or PEA. Clinically, high baseline PEA levels were linked to a sevenfold increased risk of HE after intrahepatic portosystemic shunt procedures. Our findings expand the understanding of the gut-liver-brain axis and identify a promising therapeutic and predictive target for HE.}, }
@article {pmid39779879, year = {2025}, author = {Pribyl, AL and Hugenholtz, P and Cooper, MA}, title = {A decade of advances in human gut microbiome-derived biotherapeutics.}, journal = {Nature microbiology}, volume = {10}, number = {2}, pages = {301-312}, pmid = {39779879}, issn = {2058-5276}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Biological Therapy/methods/trends ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Bacteria/genetics/classification/isolation &amp; purification ; Feces/microbiology ; Animals ; }, abstract = {Microbiome science has evolved rapidly in the past decade, with high-profile publications suggesting that the gut microbiome is a causal determinant of human health. This has led to the emergence of microbiome-focused biotechnology companies and pharmaceutical company investment in the research and development of gut-derived therapeutics. Despite the early promise of this field, the first generation of microbiome-derived therapeutics (faecal microbiota products) have only recently been approved for clinical use. Next-generation therapies based on readily culturable and as-yet-unculturable colonic bacterial species (with the latter estimated to comprise 63% of all detected species) have not yet progressed to pivotal phase 3 trials. This reflects the many challenges involved in developing a new class of drugs in an evolving field. Here we discuss the evolution of the live biotherapeutics field over the past decade, from the development of first-generation products to the emergence of rationally designed second- and third-generation live biotherapeutics. Finally, we present our outlook for the future of this field.}, }
@article {pmid39779878, year = {2025}, author = {Keskey, RC and Xiao, J and Hyoju, S and Lam, A and Kim, D and Sidebottom, AM and Zaborin, A and Dijkstra, A and Meltzer, R and Thakur, A and Zhang, K and Chen, HJ and Beloborodova, NV and Pautova, AK and Wolfe, K and Patel, B and Thewissen, R and Zaborina, O and Alverdy, JC}, title = {Enterobactin inhibits microbiota-dependent activation of AhR to promote bacterial sepsis in mice.}, journal = {Nature microbiology}, volume = {10}, number = {2}, pages = {388-404}, pmid = {39779878}, issn = {2058-5276}, support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; R01GMO62344-22//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Animals ; *Receptors, Aryl Hydrocarbon/metabolism/genetics ; Mice ; *Sepsis/microbiology/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice, Knockout ; *Enterobactin/pharmacology/metabolism ; Disease Models, Animal ; Serratia marcescens/pathogenicity/drug effects ; Macrophages/metabolism/drug effects/microbiology/immunology ; Tryptophan/metabolism ; Mice, Inbred C57BL ; *Serratia Infections/microbiology ; Cecum ; Fecal Microbiota Transplantation ; Basic Helix-Loop-Helix Transcription Factors ; }, abstract = {Sepsis is a major cause of morbidity and mortality, but our understanding of the mechanisms underlying survival or susceptibility is limited. Here, as pathogens often subvert host defence mechanisms, we hypothesized that this might influence the outcome of sepsis. We used microbiota analysis, faecal microbiota transplantation, antibiotic treatment and caecal metabolite analysis to show that gut-microbiota-derived tryptophan metabolites including indoles increased host survival in a mouse model of Serratia marcescens sepsis. Infection in macrophage-specific aryl hydrocarbon receptor (AhR) knockout mice revealed that AhR activation induced transcriptional reprogramming in macrophages and increased bacterial clearance and host survival. However, culture supernatants from multiple bacterial pathogens inhibited AhR activation in vitro. We showed that the secreted siderophore, enterobactin, inhibited AhR activation in vitro and increased sepsis mortality in vivo. By contrast, oral or systemic tryptophan supplementation increased survival. These findings show that sepsis survival depends upon the interplay between pathogen inhibition and the activation of AhR by a microbiota-derived metabolite.}, }
@article {pmid39779854, year = {2025}, author = {Won, TH and Arifuzzaman, M and Parkhurst, CN and Miranda, IC and Zhang, B and Hu, E and Kashyap, S and Letourneau, J and Jin, WB and Fu, Y and Guzior, DV and ,  and Quinn, RA and Guo, CJ and David, LA and Artis, D and Schroeder, FC}, title = {Host metabolism balances microbial regulation of bile acid signalling.}, journal = {Nature}, volume = {638}, number = {8049}, pages = {216-224}, pmid = {39779854}, issn = {1476-4687}, support = {R01 DK135816/DK/NIDDK NIH HHS/United States ; R01 AR070116/AR/NIAMS NIH HHS/United States ; R01 AI095466/AI/NIAID NIH HHS/United States ; K08 MH130773/MH/NIMH NIH HHS/United States ; DP2 HD101401/HD/NICHD NIH HHS/United States ; R01 DK132244/DK/NIDDK NIH HHS/United States ; R01 DK126871/DK/NIDDK NIH HHS/United States ; K99 AI173660/AI/NIAID NIH HHS/United States ; R01 AI151599/AI/NIAID NIH HHS/United States ; R01 DK116187/DK/NIDDK NIH HHS/United States ; R01 AI172027/AI/NIAID NIH HHS/United States ; R01 DK140854/DK/NIDDK NIH HHS/United States ; R35 GM131877/GM/NIGMS NIH HHS/United States ; U01 AI095608/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Bile Acids and Salts/metabolism/biosynthesis/chemistry ; Mice ; Receptors, Cytoplasmic and Nuclear/metabolism/antagonists &amp; inhibitors/agonists ; *Gastrointestinal Microbiome/physiology ; Amidohydrolases/metabolism ; Male ; *Signal Transduction ; Liver/metabolism ; Female ; Humans ; Mice, Inbred C57BL ; GPI-Linked Proteins ; }, abstract = {Metabolites derived from the intestinal microbiota, including bile acids (BA), extensively modulate vertebrate physiology, including development[1], metabolism[2-4], immune responses[5-7] and cognitive function[8]. However, to what extent host responses balance the physiological effects of microbiota-derived metabolites remains unclear[9,10]. Here, using untargeted metabolomics of mouse tissues, we identified a family of BA-methylcysteamine (BA-MCY) conjugates that are abundant in the intestine and dependent on vanin 1 (VNN1), a pantetheinase highly expressed in intestinal tissues. This host-dependent MCY conjugation inverts BA function in the hepatobiliary system. Whereas microbiota-derived free BAs function as agonists of the farnesoid X receptor (FXR) and negatively regulate BA production, BA-MCYs act as potent antagonists of FXR and promote expression of BA biosynthesis genes in vivo. Supplementation with stable-isotope-labelled BA-MCY increased BA production in an FXR-dependent manner, and BA-MCY supplementation in a mouse model of hypercholesteraemia decreased lipid accumulation in the liver, consistent with BA-MCYs acting as intestinal FXR antagonists. The levels of BA-MCY were reduced in microbiota-deficient mice and restored by transplantation of human faecal microbiota. Dietary intervention with inulin fibre further increased levels of both free BAs and BA-MCY levels, indicating that BA-MCY production by the host is regulated by levels of microbiota-derived free BAs. We further show that diverse BA-MCYs are also present in human serum. Together, our results indicate that BA-MCY conjugation by the host balances host-dependent and microbiota-dependent metabolic pathways that regulate FXR-dependent physiology.}, }
@article {pmid39779737, year = {2025}, author = {Corcione, S and Ferrocino, I and Lupia, T and Busca, A and Bianco, G and Dellacasa, C and Giaccone, L and Brunello, L and Butera, S and Costa, C and Bruno, B and De Rosa, FG}, title = {Influence of ESBL colonization status on gut microbiota composition during allogenic hematopoietic stem cell transplantation.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {1275}, pmid = {39779737}, issn = {2045-2322}, support = {Project no. PE00000007, INF-ACT//EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; Middle Aged ; Adult ; Prospective Studies ; Pilot Projects ; *beta-Lactamases/metabolism ; *Transplantation, Homologous/adverse effects ; Aged ; Feces/microbiology ; Italy ; Anti-Bacterial Agents/therapeutic use/pharmacology ; }, abstract = {After allogeneic HSCT (allo-HSCT), the diversity of the intestinal microbiota significantly decreases. The changes can be rapid and are thought to be caused by chemotherapy, antibiotics, or intestinal inflammation. Most patients are exposed to prophylactic and therapeutic antibiotics during neutropenia and several patients are colonized by ESBL bacteria. We investigated the changes in gut microbiota composition in allo-HSCT, aiming at investigating if the acquisition of ESBL colonization may affect gut microbiome diversity during allo-HSCT. This was a single-center prospective pilot study. All patients consecutively admitted to the Haematological Unit of the City of Health and Science, Molinette Hospital in Turin, Italy, and undergoing allo-HSCT between August 2017 to August 2020 were enrolled in the study. Microbiome analysis on fecal samples were collected every 7 days from hospital admission to discharge and until 1 year after HSCT. 48 patients were enrolled in the study. At baseline 14 patients (29.16%) were colonized by MDR bacteria, mostly extended-spectrum beta-lactamase (ESBL)-producing gram negatives (N = 11; 78.57%). During allo-HSCT, one patient had a positive rectal swab for a carbapenemase-producing Klebsiella pneumoniae and eight patients lost the colonization during the hospital stay. Microbiota composition was compared between patients colonized by ESBL at baseline and non-colonized patients. Patients colonized by ESBL had a greater abundances of Bifidobacterium, Blautia, Clostridium, Coprococcus, L-Ruminococcus Mogibacteriaceae, Peptostreptococceae and Oscillospira, while non-colonized ESBL patients had a greater abundance of Actinomycetales, Staphylococcus and Sutterella. Moreover, microbiota composition of colonized by ESBL that retained colonization after HSCT showed an increased in abundances of Akkermansia, Dialister, Erysipelotrichaceae and Methanobrevibacter when compared with patients that become negative at rectal swabs. From a clinical perspective, the evolution of this prospective pilot study will be to investigate markers of gut barrier functions, SCFA productions and to correlate the predictivity of these parameters with risk of invasive infections and clinical outcomes in allo-HSCT population.}, }
@article {pmid39778887, year = {2025}, author = {Pérez-Accino, J and Salavati, M and Glendinning, L and Salavati Schmitz, S}, title = {Effect of a single rectal fecal microbiota transplantation on clinical severity and fecal microbial communities in dogs with chronic inflammatory enteropathy.}, journal = {Journal of veterinary internal medicine}, volume = {39}, number = {1}, pages = {e17264}, pmid = {39778887}, issn = {1939-1676}, support = {//Fiona and Ian Russel Fund/ ; }, mesh = {Animals ; Dogs ; *Dog Diseases/therapy/microbiology ; *Fecal Microbiota Transplantation/veterinary ; *Feces/microbiology ; Male ; Female ; Inflammatory Bowel Diseases/veterinary/therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; Gastrointestinal Microbiome ; Chronic Disease ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been advocated as a treatment for chronic enteropathy (CE) in dogs. However, so far only short-term clinical effects have been reported whereas the effect on the microbiota remains unexplored.<br><br>HYPOTHESIS/OBJECTIVES: Assess if a single FMT enema can lead to clinical improvement in dogs with CE when accompanied by presumed favorable microbiota changes. The effect of glycerol as a cryopreservative when storing FMT preparations also was assessed.<br><br>ANIMALS: Seven dogs with CE that received FMTs from 2 healthy donor dogs.<br><br>MATERIALS AND METHODS: Six dogs received a single FMT, 1 dog received 3 consecutive FMTs. Canine chronic enteropathy clinical activity index (CCECAI) and fecal samples were obtained before (Day 0), and 7, 30 and 90&#x2009;days after FMT. Samples were stored with and without 10% glycerol. Sequencing of microbiota (16S rRNA, Illumina) was performed and compared by accepted analysis pipelines.<br><br>RESULTS: Median CCECAI before FMT was 8 (range, 5-14), decreased to a median of 3 (range, 1-12) within 1&#x2009;week and a median of 1 (range, 0-12) by Day 30 (P&#x2009;<&#x2009;.01), with an average duration of response of approximately 10&#x2009;weeks. Significant variation in the donors' microbiota composition was observed across different donations. Recipient microbiota composition or diversity did not change over time. Glycerol addition was associated with a difference in microbiota composition (P&#x2009;&#x2264;&#x2009;.001).<br><br>A single FMT can be considered&#xa0;an appropriate treatment in dogs with CE, but consistent microbiota changes were not observed.}, }
@article {pmid39778639, year = {2025}, author = {Chen, C and Wang, J and Cheng, M and Xie, H and Li, W and Zhang, C}, title = {Muribaculum intestinale-derived 3-hydroxybutyric acid from Heterophyllin B attenuated pulmonary fibrosis through IDO1-mediated ferroptosis.}, journal = {Pharmacological research}, volume = {212}, number = {}, pages = {107587}, doi = {10.1016/j.phrs.2025.107587}, pmid = {39778639}, issn = {1096-1186}, mesh = {Animals ; *Pulmonary Fibrosis/drug therapy/pathology/chemically induced/metabolism/microbiology ; Mice ; Mice, Inbred C57BL ; Humans ; *Ferroptosis/drug effects ; Male ; *Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism/genetics ; Gastrointestinal Microbiome/drug effects ; Lung/drug effects/pathology/enzymology ; Bleomycin ; Mice, Knockout ; }, abstract = {Pulmonary fibrosis (PF) is a fatal disease with increasing incidence, poor prognosis, and unclear pathogenesis. Our previous research demonstrated the beneficial effects of the natural cyclopeptide Heterophyllin B (HB) in PF. However, the precise mechanism by which HB exerts its effects in PF remains unclear. Our study revealed HB's beneficial effects in alleviating PF symptoms and restoring the intestinal mucosal barrier. Subsequently, the microbiota-dependent antifibrotic efficacy of HB was verified using various delivery routes, antibiotic treatments, and faecal microbiota transplantation. Functionally, 16S rRNA sequencing, untargeted metabolomics, and co-incubation experiments revealed that the antifibrotic efficacy of HB was primarily contingent on the enrichment of Muribaculum intestinale and its metabolite, 3-hydroxybutyric acid. Mechanistically, indoleamine 2,3- dioxygenase 1 (IDO1)-mediated ferroptosis was identified as a pivotal process in initiating PF, and the anti-fibrotic efficacy of HB relies on suppressing IDO1-mediated ferroptosis. Conversely, IDO1 deficiency alleviated the symptoms of bleomycin-induced PF and ferroptosis in mice. Coincidentally, both IDO1 overexpression and ferroptosis were observed in the pulmonary tissue of patients with idiopathic PF. Collectively, this study revealed that HB alleviates PF by eliminating intestinal microecology and metabolism and highlights the feasibility of targeting IDO1 for PF treatment.}, }
@article {pmid39777251, year = {2025}, author = {Quaglio, AE and Magro, DO and Imbrizi, M and De Oliveira, EC and Di Stasi, LC and Sassaki, LY}, title = {Creeping fat and gut microbiota in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {1}, pages = {102042}, pmid = {39777251}, issn = {2219-2840}, mesh = {Animals ; Humans ; *Crohn Disease/microbiology/immunology/therapy ; *Disease Progression ; *Dysbiosis/immunology ; *Fecal Microbiota Transplantation ; Fibrosis ; *Gastrointestinal Microbiome/physiology/immunology ; *Intra-Abdominal Fat/immunology ; Mesentery ; Prebiotics/administration &amp; dosage ; *Probiotics/therapeutic use ; }, abstract = {In this article, we explored the role of adipose tissue, especially mesenteric adipose tissue and creeping fat, and its association with the gut microbiota in the pathophysiology and progression of Crohn's disease (CD). CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, influenced by genetic predisposition, gut microbiota dysbiosis, and environmental factors. Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD. Further, visceral adipose tissue, particularly creeping fat, a mesenteric adipose tissue characterized by hypertrophy and fibrosis, has been implicated in CD pathogenesis, inflammation, and fibrosis. The bacteria from the gut microbiota may translocate into mesenteric adipose tissue, contributing to the formation of creeping fat and influencing CD progression. Although creeping fat may be a protective barrier against bacterial invasion, its expansion can damage adjacent tissues, leading to complications. Modulating gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and prebiotics has shown potential in managing CD. However, more research is needed to clarify the mechanisms linking gut dysbiosis, creeping fat, and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.}, }
@article {pmid39777148, year = {2024}, author = {An, Y and He, L and Xu, X and Piao, M and Wang, B and Liu, T and Cao, H}, title = {Gut microbiota in post-acute COVID-19 syndrome: not the end of the story.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1500890}, pmid = {39777148}, issn = {1664-302X}, abstract = {The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to major global health concern. However, the focus on immediate effects was assumed as the tip of iceberg due to the symptoms following acute infection, which was defined as post-acute COVID-19 syndrome (PACS). Gut microbiota alterations even after disease resolution and the gastrointestinal symptoms are the key features of PACS. Gut microbiota and derived metabolites disorders may play a crucial role in inflammatory and immune response after SARS-CoV-2 infection through the gut-lung axis. Diet is one of the modifiable factors closely related to gut microbiota and COVID-19. In this review, we described the reciprocal crosstalk between gut and lung, highlighting the participation of diet and gut microbiota in and after COVID-19 by destroying the gut barrier, perturbing the metabolism and regulating the immune system. Therefore, bolstering beneficial species by dietary supplements, probiotics or prebiotics and fecal microbiota transplantation (FMT) may be a novel avenue for COVID-19 and PACS prevention. This review provides a better understanding of the association between gut microbiota and the long-term consequences of COVID-19, which indicates modulating gut dysbiosis may be a potentiality for addressing this multifaceted condition.}, }
@article {pmid39776845, year = {2024}, author = {Zhuang, L and You, Y and Zeng, S and Yu, Z and Wang, H and Chen, M and Wen, W}, title = {Fecal microbiota transplantation in severe pneumonia: a case report on overcoming pan-drug resistant Klebsiella pneumoniae infection.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1451751}, pmid = {39776845}, issn = {2296-858X}, abstract = {OBJECTIVE: To evaluate the therapeutic potential of fecal microbiota transplantation (FMT) in treating severe pneumonia patients with concurrent pan-drug resistant Klebsiella pneumoniae infection.<br><br>METHODS: A case report of a 95-year-old female patient with severe pneumonia, complicated by pan-resistant bacterial infections, is presented. The patient was diagnosed with severe pneumonia caused by COVID-19, along with co-infections of Staphylococcus hominis, Enterococcus faecalis, Candida tropicalis, Pseudomonas aeruginosa, ESBL-producing pan-drug resistant Klebsiella pneumoniae and pan-resistant Acinetobacter baumannii. During hospitalization, the patient underwent comprehensive treatments, including antimicrobials, mechanical ventilation, and fiberoptic bronchoscopic alveolar lavage. FMT was administered following the failure of conventional treatments to resolve recurrent diarrhea, increased sputum production, and persistent pan-drug resistant Klebsiella pneumoniae infection.<br><br>RESULTS: Post-FMT, the patient exhibited significant clinical improvement, including reduced sputum production, cessation of diarrhea, and the normalization of respiratory symptoms. Gut microbiota analysis revealed that FMT enhanced the abundance of beneficial microbiota and suppressed Klebsiella pneumoniae, and the patient was successfully discharged after 133&#x202f;days of hospitalization.<br><br>CONCLUSION: FMT emerged as a pivotal intervention in the management of this severe pneumonia case, suggesting its efficacy in restoring gut microbiota balance and aiding recovery from multi-drug-resistant infections. This case underscores the potential of FMT as a therapeutic option in severe pulmonary infections, especially in the context of antibiotic resistance in severe pneumonia patients.}, }
@article {pmid39776440, year = {2024}, author = {Fang, L and Ning, J}, title = {Recent advances in gut microbiota and thyroid disease: pathogenesis and therapeutics in autoimmune, neoplastic, and nodular conditions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1465928}, pmid = {39776440}, issn = {2235-2988}, mesh = {Animals ; Humans ; Bacteria/classification/metabolism ; Dysbiosis/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Neoplasms/microbiology/pathology/therapy ; *Probiotics/administration &amp; dosage ; *Thyroid Diseases/immunology/microbiology/pathology/therapy ; }, abstract = {This review synthesizes key findings from the past five years of experimental literature, elucidating the gut microbiome's significant influence on the pathogenesis of thyroid diseases. A pronounced shift in the gut microbiota composition has been consistently observed, with a significant reduction in bacteria such as Bifidobacterium, Bacillaceae, Megamonas, and Clostridium, and a notable increase in bacteria, including Bacteroides, Proteobacteria, Actinobacteria, Desulfobacterota, and Klebsiella. These alterations are implicated in the development and progression of thyroid diseases by impacting metabolic pathways including bile acid and cytokine production, including a decrease in short-chain fatty acids (SCFAs) that are crucial for immune regulation and thyroid hormone homeostasis. The review also highlights the therapeutic implications of probiotics in managing thyroid conditions. Evidence suggests that probiotic adjunct therapy can modulate the gut microbiota, leading to improvements in thyroid function and patient outcomes. The use of specific probiotic strains, such as Lactiplantibacillus plantarum 299v and Bifidobacterium longum, has demonstrated potential in enhancing the effects of traditional treatments and possibly restoring a balanced gut microbiota. Notably, fecal microbiota transplantation (FMT) has emerged as a promising intervention in Graves' Disease (GD), demonstrating the potential to recalibrate the gut microbiota, thereby influencing neurotransmitters and trace elements via the gut-brain and gut-thyroid axes. The integration of microbiome-based therapies with traditional treatments is anticipated to usher in a new era of personalized thyroid disease management, offering a more nuanced approach to patient care. By integrating this body of work, the review offers an innovative perspective on the gut microbiome's broad impact on thyroid diseases and the therapeutic applications of probiotics.}, }
@article {pmid39775925, year = {2025}, author = {Bloem, MN and Baaleman, DF and Thapar, N and Roberts, SE and Koppen, IJN and Benninga, MA}, title = {Prevalence of functional defecation disorders in European children: A systematic review and meta-analysis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {80}, number = {4}, pages = {580-597}, pmid = {39775925}, issn = {1536-4801}, support = {//None/ ; }, mesh = {Humans ; Prevalence ; Europe/epidemiology ; *Constipation/epidemiology ; Child ; Child, Preschool ; Infant ; Adolescent ; *Fecal Incontinence/epidemiology ; Female ; Male ; Infant, Newborn ; Cross-Sectional Studies ; Defecation ; }, abstract = {OBJECTIVES: Functional defecation disorders (FDDs) are common among children worldwide. The prevalence of these disorders has not been clearly described in Europe. This study performed a systematic review and meta-analysis on the prevalence of FDD in European children and assessed geographical, age, and sex distribution and associated factors.<br><br>METHODS: PubMed, Embase, Psycinfo, Cochrane Library, and Cinahl were searched from 1999 to July 2023. Included studies were (1) prospective or cross-sectional studies of European population-based samples; (2) reporting the prevalence of infant dyschezia (ID) according to Rome II, III, or IV criteria or functional constipation (FC) or functional non-retentive fecal incontinence (FNRFI) according to Rome III or IV criteria; (3) aged 0-18 years; and (4) published in English, Dutch or Spanish. PRISMA guidelines for extracting data and assessing data quality were followed.<br><br>RESULTS: Twenty-eight studies were included. Pooled prevalence was 6.9% (95% confidence interval [CI]: 3.1%-11.9%) for ID in infants 0-12 months (9 studies, n&#x2009;=&#x2009;5611), 8.17% (95% CI: 6.33%-10.22%) for FC in children <4 years (25 studies, n&#x2009;=&#x2009;35,189), 11.39% (95% CI: 9.34%-14.11%) for FC in children 4-18 years, and 0.24% (95% CI: 0.07%-0.49%) for FNRFI in children 4-18 years (7 studies, n&#x2009;=&#x2009;16,873). No sex predominance was found for FC. FC prevalence did not differ significantly when diagnosed according to Rome III versus IV. FC prevalence differed between countries, with greatest rates in Italy, Germany, and Spain. No meta-analysis could be performed on other factors associated with FDD.<br><br>CONCLUSIONS: FDD is common in European children. Future longitudinal studies are needed to provide better insight into associated factors in pathogenesis.}, }
@article {pmid39775370, year = {2025}, author = {Lai, Y and Qiu, R and Zhou, J and Ren, L and Qu, Y and Zhang, G}, title = {Fecal Microbiota Transplantation Alleviates Airway Inflammation in Asthmatic Rats by Increasing the Level of Short-Chain Fatty Acids in the Intestine.}, journal = {Inflammation}, volume = {}, number = {}, pages = {}, pmid = {39775370}, issn = {1573-2576}, support = {(No. 2021JJ30513, No. 2017JJ3245)//Natural Science Foundation of Hunan Province/ ; No. 20B444//Education Department of Hunan Province/ ; (No. 81603705)//National Natural Science Foundation of China/ ; (No. 2017M612567)//Postdoctoral Science Foundation of China/ ; (2024XJZA008)//Hunan University of Chinese Medicine research project/ ; }, abstract = {Asthma is a prevalent chronic inflammatory disorder of the respiratory tract that not only manifests with respiratory symptoms but also often involves intestinal flora disorders and gastrointestinal dysfunction. Recent studies have confirmed the close relationship between the gut and lungs, known as the "gut-lung axis" theory. Fecal microbiota transplantation (FMT), a method for restoring normal intestinal flora, has shown promise in treating common gastrointestinal diseases. The "gut-lung axis" theory suggests that FMT may have significant therapeutic potential for asthma. In this study, we established an Ovalbumin (OVA)-induced rat model of asthma to investigate the protective effect of FMT on airway inflammation and the restoration of intestinal short-chain fatty acids (SCFAs), aiming to explore its underlying mechanism. Rats in the Control group underwent fecal treatment via gavage (Control-FMT, C-FMT group), while rats in the Asthma group underwent fecal treatment via gavage after asthma induction (Asthma-FMT, A-FMT group). Following a two-week period of continuous intragastric administration, various measurements were conducted to assess pulmonary function, peripheral blood neutrophil, lymphocyte, and eosinophil content, lung tissue pathology, and collagen fiber deposition in the lungs. Additionally, neutrophil and eosinophil content in bronchoalveolar lavage fluid (BALF), expression levels of Interleukin-4 (IL-4), IL-5, IL-13, IL-17, IL-33, leukotrienes (LT), thymic stromal lymphopoietin (TSLP), prostaglandin D2 (PGD2) protein and mRNA in lung tissue, and SCFAs content in stool were evaluated. In the C-FMT group, lung function significantly improved, inflammatory cell content in peripheral blood and BALF decreased, lung tissue pathology and collagen fiber deposition significantly improved, the protein and mRNA levels of lung inflammatory factors IL-4, IL-5, IL-13, IL-17, IL-33, LT, TSLP, PGD2 were significantly decreased, and SCFAs such as acetate (C2), propionate (C3), butyrate (C4), isobutyric acid (I-C4), valeric acid (C5), and isovaleric acid (I-C5) content in stool significantly increased. However, the indexes in the A-FMT group did not show significant recovery, and the treatment effect on asthma symptoms in rats was inferior to that in the C-FMT group. Asthma induced intestinal flora disorders in rats, and FMT treatment improved the inflammatory response in asthmatic rat models and corrected their intestinal SCFAs disorders. Encouraging the recovery of intestinal SCFAs may play a significant role, and beneficial bacteria present in feces may improve asthma symptoms by promoting the remodeling of intestinal flora. This experiment provides further scientific evidence supporting the "gut-lung axis" theory.}, }
@article {pmid39773995, year = {2024}, author = {Mullish, BH and Innes, AJ and Roberts, LA and Anim-Burton, S and Webber, L and Johnson, NA and Ghani, R and Farshi, P and Khan, AB and Kinsella, F and Kottaridis, P and Krishnamurthy, P and Nicholson, E and Palanicawandar, R and Wheeler, G and Davies, F and Marchesi, JR and Pavlů, J}, title = {Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial.}, journal = {BMJ open}, volume = {14}, number = {12}, pages = {e093120}, pmid = {39773995}, issn = {2044-6055}, mesh = {Adult ; Female ; Humans ; Male ; Clinical Trials, Phase II as Topic ; Double-Blind Method ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Hematologic Neoplasms/therapy ; *Hematopoietic Stem Cell Transplantation ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Transplantation Conditioning/methods ; *Transplantation, Homologous ; }, abstract = {INTRODUCTION: Lower diversity of the gut microbiome prior to allogeneic haematopoietic cell transplantation (HCT) correlates with reduced survival after the intervention. Most patients undergoing HCT for a haematological malignancy have previously received intensive chemotherapy, resulting in prolonged neutropenic episodes requiring broad-spectrum antibiotics; use of these has been linked to reduced microbiome diversity. Intestinal microbiota transplant (IMT) is a novel treatment approach that restores this diversity. We hypothesised that IMT performed prior to initiation of HCT conditioning restores microbiome diversity during the early stages of HCT, leading to decreased frequency of complications and improved outcomes of HCT.<br><br>METHODS AND ANALYSIS: 50 adult patients receiving allogeneic HCT will be recruited into this phase IIa trial and randomised 1:1 to receive capsulised IMT or matched placebo shortly prior to initiation of HCT conditioning and followed for up to 12 months. The primary outcome will be to assess the increase in alpha diversity between pre-IMT and that measured at ~42 days after IMT administration (day +28 of HCT), comparing the difference between patients receiving IMT compared with placebo. Secondary outcomes will include tolerability, the dynamics of gut microbiome diversity metrics and taxonomy over all time points assessed, as well as clinical outcomes (including burden of invasive infections, days of fever, admission to intensive care, development of graft-vs-host disease and mortality).<br><br>ETHICS AND DISSEMINATION: This study was approved by a UK Research Ethics Committee (REC reference: 23/NE/0105). Dissemination of results will be in concert with patient and public involvement group input and is expected to be primarily via abstract presentation at conferences and manuscripts in peer-reviewed journals.<br><br>TRIAL REGISTRATION NUMBERS: NCT6355583; EudraCT: 2022-003617-10.}, }
@article {pmid39773539, year = {2025}, author = {Zeng, J and Zhao, D and Way, G and Fagan, A and Fuchs, M and Puri, P and Davis, BC and Wang, X and Gurley, EC and Hylemon, PB and Fan, JG and Sikaroodi, M and Gillevet, PM and Zhou, H and Bajaj, JS}, title = {Intestinal mucosal mitochondrial oxidative phosphorylation worsens with cirrhosis progression and is ameliorated with fecal microbiota transplantation.}, journal = {JCI insight}, volume = {10}, number = {4}, pages = {}, pmid = {39773539}, issn = {2379-3708}, support = {IS1 BX005517/BX/BLRD VA/United States ; IK6 BX004477/BX/BLRD VA/United States ; R01 AA030180/AA/NIAAA NIH HHS/United States ; I01 BX005730/BX/BLRD VA/United States ; IS1 BX004777/BX/BLRD VA/United States ; R01 DK139587/DK/NIDDK NIH HHS/United States ; R56 DK115377/DK/NIDDK NIH HHS/United States ; }, mesh = {*Fecal Microbiota Transplantation/methods ; *Oxidative Phosphorylation ; *Liver Cirrhosis/metabolism/therapy/pathology/microbiology ; *Intestinal Mucosa/metabolism/microbiology/pathology ; Humans ; Disease Progression ; *Mitochondria/metabolism ; Male ; Animals ; Mice ; Gastrointestinal Microbiome ; Female ; }, abstract = {Cirrhosis, the end-stage of liver disease, progresses through altered gut-liver axis and microbial change. Here we show that intestinal mucosal mitochondrial oxidative phosphorylation, which affects intestinal barrier worsens with cirrhosis progression. This is ameliorated with fecal microbiota transplantation.}, }
@article {pmid39773319, year = {2025}, author = {Prince, N and Peralta Marzal, LN and Roussin, L and Monnoye, M and Philippe, C and Maximin, E and Ahmed, S and Salenius, K and Lin, J and Autio, R and Adolfs, Y and Pasterkamp, RJ and Garssen, J and Naudon, L and Rabot, S and Kraneveld, AD and Perez-Pardo, P}, title = {Mouse strain-specific responses along the gut-brain axis upon fecal microbiota transplantation from children with autism.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447822}, pmid = {39773319}, issn = {1949-0984}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; Male ; *Mice, Inbred C57BL ; *Brain-Gut Axis/physiology ; *Mice, Inbred BALB C ; Child ; Autism Spectrum Disorder/microbiology ; Dysbiosis/microbiology ; Feces/microbiology ; Disease Models, Animal ; Autistic Disorder/microbiology/physiopathology ; Female ; Social Behavior ; Species Specificity ; Bacteria/classification/isolation &amp; purification/genetics/metabolism ; }, abstract = {Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.}, }
@article {pmid39772953, year = {2025}, author = {Teigen, LM and Hoeg, A and Zehra, H and Shah, P and Johnson, R and Hutchison, K and Kocher, M and Lin, AW and Johnson, AJ and Vaughn, BP}, title = {Nutritional optimization of fecal microbiota transplantation in humans: a scoping review.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446378}, pmid = {39772953}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Diet ; Clostridium Infections/therapy/microbiology ; Feces/microbiology ; Dietary Supplements ; }, abstract = {Diet constitutes a major source of nutrient flow to the gut microbes. As such, it can be used to help shape the gut microbiome. Fecal microbiota transplantation (FMT) is an increasingly promising therapy in disease states beyond recurrent Clostridioides difficile infection, but diet is largely overlooked for its potential to help optimize this therapy. Therefore, the aim of this scoping review is to present the literature landscape that captures pre- and post-FMT dietary intake in humans, identify research gaps, and provide recommendations for future research. A comprehensive search strategy was developed and searches were run in five databases. Studies were included if they discussed adults who underwent FMT for any recognized treatment indication and had dietary intake as a study objective, this search encompassed studies with interventions that included foods and dietary supplements. The initial screening identified a total of 7721 articles, of which 18 met the inclusion criteria for this review. Studies were heterogeneous, but taken together, they introduce a framework that defines important nutritional considerations for both donors and FMT recipients in the period around FMT dosing. This framework is summarized with this review and highlights the opportunities available to develop FMT-based precision nutrition strategies to optimize its clinical efficacy.}, }
@article {pmid39772388, year = {2025}, author = {Wouters, S and Moors, H and Verslegers, M and Leys, N and Malhotra-Kumar, S and Kumar-Singh, S and Mysara, M}, title = {Protocol for fecal microbiota transplantation: A microaerophilic approach for mice housed in a specific pathogen-free facility.}, journal = {STAR protocols}, volume = {6}, number = {1}, pages = {103517}, pmid = {39772388}, issn = {2666-1667}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Mice ; *Feces/microbiology ; Specific Pathogen-Free Organisms ; Housing, Animal ; Female ; }, abstract = {Recently, studies have emerged exploring the potential application of fecal microbiota transplantation (FMT) in pre-clinical settings. Here, we present a protocol for FMT for mice housed in a specific pathogen-free (SPF) facility. We describe steps for sample collection, microaerophilic processing of freshly collected fecal pellets, and administration through oral gavage. We then detail procedures for the engraftment of the bacterial community. This protocol focuses on age- and gender-matched, healthy donor mice using a mobile and cost-effective alternative to an anoxic cabinet.}, }
@article {pmid39771031, year = {2024}, author = {Brusnic, O and Adrian, B and Sorin-Radu, F and Grama, B and Sofonea, F and Roman-Filip, C and Roman-Filip, I and Solomon, A and Bîrsan, S and Dura, H and Porr, C and Adrian, C and Onisor, DM}, title = {Importance of Fecal Microbiota Transplantation and Molecular Regulation as Therapeutic Strategies in Inflammatory Bowel Diseases.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, pmid = {39771031}, issn = {2072-6643}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Inflammatory Bowel Diseases/therapy/microbiology/immunology ; *MicroRNAs/metabolism ; *Gastrointestinal Microbiome ; Gene Expression Regulation ; Animals ; Intestinal Mucosa/microbiology/metabolism/immunology ; }, abstract = {Noncoding RNAs, particularly microRNAs (miRNAs) and small interfering RNAs (siRNAs), have emerged as key players in the pathogenesis and therapeutic strategies for inflammatory bowel disease (IBD). MiRNAs, small endogenous RNA molecules that silence target mRNAs to regulate gene expression, are closely linked to immune responses and inflammatory pathways in IBD. Notably, miR-21, miR-146a, and miR-155 are consistently upregulated in IBD, influencing immune cell modulation, cytokine production, and the intestinal epithelial barrier. These miRNAs serve as biomarkers for disease progression and severity, as well as therapeutic targets for controlling inflammation. This comprehensive review highlights the intricate interplay between the gut microbiota, fecal microbiota transplantation (FMT), and miRNA regulation. It concludes that microbiota and FMT influence miRNA activity, presenting a promising avenue for personalized IBD treatment.}, }
@article {pmid39771027, year = {2024}, author = {Gruenbaum, BF and Merchant, KS and Zlotnik, A and Boyko, M}, title = {Gut Microbiome Modulation of Glutamate Dynamics: Implications for Brain Health and Neurotoxicity.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, pmid = {39771027}, issn = {2072-6643}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Glutamic Acid/metabolism ; *Brain-Gut Axis/physiology ; *Brain/metabolism ; Animals ; Fecal Microbiota Transplantation ; Blood-Brain Barrier/metabolism ; Neurotoxicity Syndromes/etiology/metabolism ; Depression/metabolism/microbiology ; }, abstract = {The gut-brain axis plays an integral role in maintaining overall health, with growing evidence suggesting its impact on the development of various neuropsychiatric disorders, including depression. This review explores the complex relationship between gut microbiota and glutamate (Glu) regulation, highlighting its effect on brain health, particularly in the context of depression following certain neurological insults. We discuss how microbial populations can either facilitate or limit Glu uptake, influencing its bioavailability and predisposing to neuroinflammation and neurotoxicity. Additionally, we examine the role of gut metabolites and their influence on the blood-brain barrier and neurotransmitter systems involved in mood regulation. The therapeutic potential of microbiome-targeted interventions, such as fecal microbiota transplantation, is also highlighted. While much research has explored the role of Glu in major depressive disorders and other neurological diseases, the contribution of gut microbiota in post-neurological depression remains underexplored. Future research should focus on explaining the mechanisms linking the gut microbiota to neuropsychiatric outcomes, particularly in conditions such as post-stroke depression, post-traumatic brain-injury depression, and epilepsy-associated depression. Systematic reviews and human clinical studies are needed to establish causal relationships and assess the efficacy of microbiome-targeted therapies in improving the neuropsychiatric sequalae after neurological insults.}, }
@article {pmid39770958, year = {2024}, author = {Puca, P and Del Gaudio, A and Becherucci, G and Sacchetti, F and Sofo, L and Lopetuso, LR and Papa, A and Cammarota, G and Scaldaferri, F}, title = {Diet and Microbiota Modulation for Chronic Pouchitis: Evidence, Challenges, and Opportunities.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, pmid = {39770958}, issn = {2072-6643}, mesh = {*Pouchitis/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Chronic Disease ; *Probiotics/therapeutic use ; *Prebiotics/administration &amp; dosage ; Colitis, Ulcerative/microbiology/therapy ; Proctocolectomy, Restorative/adverse effects ; Diet/methods ; Diet, Mediterranean ; }, abstract = {Chronic pouchitis occurs in about 50% of patients undergoing a restorative proctocolectomy for ulcerative colitis. This affection represents a significant therapeutic challenge, particularly for symptomatic patients who do not respond to antibiotic treatments and biologic therapies. Several dietary approaches, including low FODMAP diets and the Mediterranean diet, have shown promising results in improving symptoms and disease burden. The rationale for dietary intervention lies in the reduction in inflammation and modulation of gut microbiota. However, conflicting results and methodological heterogeneity jeopardize the transition of these approaches from the field of research to clinical practice. Together with a nutritional approach, innovative methods of microbiota modulation, including probiotics and fecal microbiota transplantation, are emerging as safe and effective strategies in managing chronic pouchitis. This narrative review analyzes recent advancements in nutritional therapies and microbiota modulation as innovative and complementary approaches for managing chronic pouchitis. After examining microbiota modulation strategies, specifically the effectiveness of probiotics, prebiotics, and fecal microbiota transplantation in restoring microbial diversity and their potential role in alleviating symptoms, the review assesses the available clinical evidence concerning dietary interventions and their impact on gut microbiota. A comprehensive understanding of interventions aimed at modulating the microbiota is crucial for enhancing the effectiveness of conventional therapies. Such strategies may lead to significant improvements in patients' quality of life and their perception of the disease. However, the variability in microbiota composition, the use of restrictive diets, and the lack of standardized methods for evaluating these interventions remain significant challenges. Future research is essential to improve our understanding of the underlying mechanisms and optimize clinical application.}, }
@article {pmid39770742, year = {2024}, author = {Park, SH and Lee, JH and Lee, S and Shin, J and Cha, B and Hong, JT and Kwon, KS}, title = {Factors for Treatment Failure After Fecal Microbiota Transplantation in Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, pmid = {39770742}, issn = {2076-2607}, support = {2023AR05//Seoul Clinical Laboratories/ ; }, abstract = {Recently, fecal microbiota transplantation (FMT) has been introduced as an effective treatment option for Clostridioides difficile infection (CDI). However, the risk factors associated with FMT treatment failure have not been well demonstrated. Therefore, we aimed to investigate the risk factors of treatment failure or recurrence after FMT for CDI. This retrospective study included 124 patients with CDI who underwent FMT at Inha University Hospital between November 2017 and August 2021 and were followed up for 8 weeks after FMT for symptoms of CDI. FMT failure was defined as diarrhea recurrence or a positive stool test. We assessed the risk factors for treatment failure, including comorbidities, antibiotic use pre- and post-FMT, and the number of CDI episodes before FMT. Ninety-three patients (75%) experienced symptom improvement <7 days after FMT, while treatment failure occurred in 40 patients (32.3%). Multivariate analysis revealed that males had a lower symptom improvement rate <7 days after FMT (p = 0.049). Patients using antibiotics after FMT showed a higher rate of recurrence or treatment failure in <8 weeks (p = 0.032). Patients requiring antibiotics after FMT should be considered at higher risk of treatment failure. Careful antibiotic stewardship, particularly minimizing non-essential antibiotic use before and after FMT, may significantly enhance treatment outcomes. Further large-scale prospective studies are warranted to confirm these findings and develop targeted antibiotic management protocols for improving the efficacy of FMT in CDI treatment.}, }
@article {pmid39770703, year = {2024}, author = {Islam, MZ and Jozipovic, D and Lopez, PA and Krych, L and Correia, BSB and Bertram, HC and Hansen, AK and Hansen, CHF}, title = {Wild-Mouse-Derived Gut Microbiome Transplantation in Laboratory Mice Partly Alleviates House-Dust-Mite-Induced Allergic Airway Inflammation.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, pmid = {39770703}, issn = {2076-2607}, support = {R288-2018-1123//Lundbeck Foundation/ ; N/A//Sigrid Rigmor Morans Mindefond/ ; }, abstract = {Laboratory mice are instrumental for preclinical research but there are serious concerns that the use of a clean standardized environment for specific-pathogen-free (SPF) mice results in poor bench-to-bedside translation due to their immature immune system. The aim of the present study was to test the importance of the gut microbiota in wild vs. SPF mice for evaluating host immune responses in a house-dust-mite-induced allergic airway inflammation model without the influence of pathogens. The wild mouse microbiome reduced histopathological changes and TNF-α in the lungs and serum when transplanted to microbiota-depleted mice compared to mice transplanted with the microbiome from SPF mice. Moreover, the colonic gene expression of Gata3 was significantly lower in the wild microbiome-associated mice, whereas Muc1 was more highly expressed in both the ileum and colon. Intestinal microbiome and metabolomic analyses revealed distinct profiles associated with the wild-derived microbiome. The wild-mouse microbiome thus partly reduced sensitivity to house-dust-mite-induced allergic airway inflammation compared to the SPF mouse microbiome, and preclinical studies using this model should consider using both 'dirty' rewilded and SPF mice for testing new therapeutic compounds due to the significant effects of their respective microbiomes and derived metabolites on host immune responses.}, }
@article {pmid39770634, year = {2024}, author = {Chun, M and Tun, KM and Vongsavath, T and Verma, R and Batra, K and Limsui, D and Jenkins, E}, title = {Fecal Microbiota Transplantation for Chronic Pouchitis: A Systematic Review and Meta-Analysis.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, pmid = {39770634}, issn = {2076-2607}, abstract = {Pouchitis is a common complication after ileal-pouch anal anastomosis in patients with medically refractory ulcerative colitis. There has been a lack of high-level evidence focusing on the safety and efficacy outcomes of fecal microbiota transplantation (FMT). We aim to evaluate outcomes and complications of fecal microbiota transplantation (FMT) for chronic pouchitis. Databases were systematically searched to retrieve English-only, original studies, published from inception to 31 March 2024, investigating chronic pouchitis only. Primary outcomes included overall remission, clinical response, remission, relapse, and complications. Seven studies with 94 patients were included. The pooled overall remission rate was 15% (95% CI: 0-29%, p < 0.001), the clinical response rate was 33% (95% CI: 19-46%, p = 0.14), the clinical remission rate was 14% (95% CI: 19-46%, p < 0.001), and the clinical relapse rate was 36% (95% CI: 16-55%, p = 0.11). The pooled proportion of patients with mild adverse events after FMT treatment was 39% (95% CI: 6-71%, p < 0.001). No severe adverse events or deaths were reported. Although FMT is an effective treatment for chronic pouchitis, there is still a high rate of mild adverse events. High-level evidence for FMT is still sparse, limiting recommendations for clinical use.}, }
@article {pmid39767682, year = {2024}, author = {Farhadi Rad, H and Tahmasebi, H and Javani, S and Hemati, M and Zakerhamidi, D and Hosseini, M and Alibabaei, F and Banihashemian, SZ and Oksenych, V and Eslami, M}, title = {Microbiota and Cytokine Modulation: Innovations in Enhancing Anticancer Immunity and Personalized Cancer Therapies.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, pmid = {39767682}, issn = {2227-9059}, abstract = {The gut microbiota plays a crucial role in modulating anticancer immunity, significantly impacting the effectiveness of various cancer therapies, including immunotherapy, chemotherapy, and radiotherapy. Its impact on the development of cancer is complex; certain bacteria, like Fusobacterium nucleatum and Bacteroides fragilis, can stimulate the growth of tumors by causing immunological evasion and inflammation, while advantageous strains, like Faecalibaculum rodentium, have the ability to suppress tumors by modifying immune responses. Cytokine activity and immune system regulation are intimately related. Cytokines including TGF-β, IL-6, and IL-10 promote tumor development by inhibiting efficient immune surveillance. The gut microbiome exhibits a delicate balance between pro- and anti-tumorigenic factors, as evidenced by the enhancement of anti-tumor immunity by cytokines such as IL-12 and IFN-γ. Improved immunotherapy responses are linked to a diverse microbiota, which is correlated with higher tumor infiltration and cytotoxic T-cell activation. Because microbial metabolites, especially short-chain fatty acids, affect cytokine expression and immune cell activation inside the tumor microenvironment, this link highlights the need to maintain microbial balance for optimal treatment effects. Additionally, through stimulating T-cell activation, bacteria like Lactobacillus rhamnosus and Bifidobacterium bifidum increase cytokine production and improve the efficacy of immune checkpoint inhibitors (ICIs). An option for overcoming ICI resistance is fecal microbiota transplantation (FMT), since research suggests that it improves melanoma outcomes by increasing CD8+ T-cell activation. This complex interaction provides an opportunity for novel cancer therapies by highlighting the possibility of microbiome modification as a therapeutic approach in personalized oncology approaches.}, }
@article {pmid39767577, year = {2024}, author = {Munteanu, C and Onose, G and Rotariu, M and Poștaru, M and Turnea, M and Galaction, AI}, title = {Role of Microbiota-Derived Hydrogen Sulfide (H2S) in Modulating the Gut-Brain Axis: Implications for Alzheimer's and Parkinson's Disease Pathogenesis.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, pmid = {39767577}, issn = {2227-9059}, support = {CNFIS - FDI - 2024 - F - 0099//Supporting the institutional capacity for research and innovation through transdisciplinary biotechnologies (InovBiotech)/ ; }, abstract = {Microbiota-derived hydrogen sulfide (H2S) plays a crucial role in modulating the gut-brain axis, with significant implications for neurodegenerative diseases such as Alzheimer's and Parkinson's. H2S is produced by sulfate-reducing bacteria in the gut and acts as a critical signaling molecule influencing brain health via various pathways, including regulating inflammation, oxidative stress, and immune responses. H2S maintains gut barrier integrity at physiological levels and prevents systemic inflammation, which could impact neuroinflammation. However, as H2S has a dual role or a Janus face, excessive H2S production, often resulting from gut dysbiosis, can compromise the intestinal barrier and exacerbate neurodegenerative processes by promoting neuroinflammation and glial cell dysfunction. This imbalance is linked to the early pathogenesis of Alzheimer's and Parkinson's diseases, where the overproduction of H2S exacerbates beta-amyloid deposition, tau hyperphosphorylation, and alpha-synuclein aggregation, driving neuroinflammatory responses and neuronal damage. Targeting gut microbiota to restore H2S homeostasis through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation presents a promising therapeutic approach. By rebalancing the microbiota-derived H2S, these strategies may mitigate neurodegeneration and offer novel treatments for Alzheimer's and Parkinson's diseases, underscoring the critical role of the gut-brain axis in maintaining central nervous system health.}, }
@article {pmid39766423, year = {2024}, author = {Menezes, AA and Shah, ZA}, title = {A Review of the Consequences of Gut Microbiota in Neurodegenerative Disorders and Aging.}, journal = {Brain sciences}, volume = {14}, number = {12}, pages = {}, pmid = {39766423}, issn = {2076-3425}, support = {R01 NS112642/NS/NINDS NIH HHS/United States ; R01NS112642/NS/NINDS NIH HHS/United States ; }, abstract = {Age-associated alterations in the brain lead to cognitive deterioration and neurodegenerative disorders (NDDs). This review with a particular focus on Alzheimer's disease (AD), emphasizes the burgeoning significance of the gut microbiota (GMB) in neuroinflammation and its impact on the gut-brain axis (GBA), a communication conduit between the gut and the central nervous system (CNS). Changes in the gut microbiome, including diminished microbial diversity and the prevalence of pro-inflammatory bacteria, are associated with AD pathogenesis. Promising therapies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, may restore gut health and enhance cognitive performance. Clinical data remain insufficient, necessitating further research to elucidate causes, enhance therapy, and consider individual variances. This integrative approach may yield innovative therapies aimed at the GMB to improve cognitive function and brain health in older people.}, }
@article {pmid39766170, year = {2024}, author = {Ciernikova, S and Sevcikova, A and Novisedlakova, M and Mego, M}, title = {Insights into the Relationship Between the Gut Microbiome and Immune Checkpoint Inhibitors in Solid Tumors.}, journal = {Cancers}, volume = {16}, number = {24}, pages = {}, pmid = {39766170}, issn = {2072-6694}, support = {1/0071/24//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; 2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, abstract = {Immunotherapy with immune checkpoint inhibitors represents a revolutionary approach to the treatment of solid tumors, including malignant melanoma, lung cancer, and gastrointestinal malignancies. Anti-CTLA-4 and anti-PD-1/PDL-1 therapies provide prolonged survival for cancer patients, but their efficacy and safety are highly variable. This review focuses on the crucial role of the gut microbiome in modulating the efficacy and toxicity of immune checkpoint blockade. Studies suggest that the composition of the gut microbiome may influence the response to immunotherapy, with specific bacterial strains able to promote an anti-tumor immune response. On the other hand, dysbiosis may increase the risk of adverse effects, such as immune-mediated colitis. Interventions aimed at modulating the microbiome, including the use of probiotics, prebiotics, fecal microbial transplantation, or dietary modifications, represent promising strategies to increase treatment efficacy and reduce toxicity. The combination of immunotherapy with the microbiome-based strategy opens up new possibilities for personalized treatment. In addition, factors such as physical activity and nutritional supplementation may indirectly influence the gut ecosystem and consequently improve treatment outcomes in refractory patients, leading to enhanced patient responses and prolonged survival.}, }
@article {pmid39766032, year = {2024}, author = {Altrawy, A and Khalifa, MM and Abdelmaksoud, A and Khaled, Y and Saleh, ZM and Sobhy, H and Abdel-Ghany, S and Alqosaibi, A and Al-Muhanna, A and Almulhim, J and El-Hashash, A and Sabit, H and Arneth, B}, title = {Metabolites in the Dance: Deciphering Gut-Microbiota-Mediated Metabolic Reprogramming of the Breast Tumor Microenvironment.}, journal = {Cancers}, volume = {16}, number = {24}, pages = {}, pmid = {39766032}, issn = {2072-6694}, abstract = {Breast cancer (BC), a major cause of death among women worldwide, has traditionally been linked to genetic and environmental factors. However, emerging research highlights the gut microbiome's significant role in shaping BC development, progression, and treatment outcomes. This review explores the intricate relationship between the gut microbiota and the breast tumor microenvironment, emphasizing how these microbes influence immune responses, inflammation, and metabolic pathways. Certain bacterial species in the gut either contribute to or hinder BC progression by producing metabolites that affect hormone metabolism, immune system pathways, and cellular signaling. An imbalance in gut bacteria, known as dysbiosis, has been associated with a heightened risk of BC, with metabolites like short-chain fatty acids (SCFAs) and enzymes such as β-glucuronidase playing key roles in this process. Additionally, the gut microbiota can impact the effectiveness of chemotherapy, as certain bacteria can degrade drugs like gemcitabine and irinotecan, leading to reduced treatment efficacy. Understanding the complex interactions between gut bacteria and BC may pave the way for innovative treatment approaches, including personalized microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, offering new hope for more effective prevention, diagnosis, and treatment of BC.}, }
@article {pmid39765038, year = {2025}, author = {Wang, C and Peng, M and Gao, Z and Fu, F and Li, G and Su, D and Huang, L and Guo, J and Shan, Y}, title = {Citrus aurantium 'Changshan-huyou' physiological premature fruit drop: A promising prebiotic to tackle obesity.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {136}, number = {}, pages = {156347}, doi = {10.1016/j.phymed.2024.156347}, pmid = {39765038}, issn = {1618-095X}, mesh = {Animals ; *Citrus/chemistry ; *Obesity/prevention &amp; control/drug therapy ; Gastrointestinal Microbiome/drug effects ; Diet, High-Fat/adverse effects ; *Prebiotics ; Fruit/chemistry ; Mice ; Mice, Inbred C57BL ; Male ; *Anti-Obesity Agents/pharmacology ; Flavonoids/pharmacology/analysis ; Fecal Microbiota Transplantation ; Volatile Organic Compounds/analysis/pharmacology ; }, abstract = {BACKGROUND: Presently, the mitigation and governance of obesity have surfaced as significant public health dilemmas on a global scale. A wealth of studies indicated that the host gut microbiota is instrumental in regulating the interplay between high-fat diet (HFD) intake and the pathogenesis of obesity. Physiological premature fruit drop, a major byproduct of citrus, is rich in a variety of bioactive constituents, yet its potential has remained underutilized for an extended period.<br><br>PURPOSE: The objective of this investigation is to examine the chemical constituents of Citrus aurantium'Changshan-huyou' premature fruit drop (HYFD) and investigate its anti-obesity effects, elucidating its potential pathways.<br><br>METHODS: Volatile compounds and flavonoids in HYFD were analyzed using chromatographic and mass spectrometric techniques. Furthermore, this study utilized biochemical assays and histopathological examinations to evaluate the effects of HYFD on HFD-fed mice. The impact of HYFD on the gut microbiota of the mice was examined through 16S rRNA gene sequencing, and fecal microbiota transplantation was employed to validate the role of the gut microbial community in host obesity prevention. Concurrently, transcriptome was employed to identify differentially expressed genes, providing further insights into the molecular mechanisms through which HYFD manifests its anti-obesity effects.<br><br>RESULTS: Our findings demonstrated that HYFD supplementation significantly alleviated adiposity and ameliorated the dysbiosis of gut microbiota in HFD-induced mice. HYFD rectified the HFD-induced gut microbiota dysregulation, enhanced the presence of beneficial microbial taxa linked to lipid metabolism, including Parabacteroides and Alistipes, and elevated concentrations of the anti-obesity short-chain fatty acids, comprising caproic acid and isocaproic acid. Additionally, transcriptomic analyses confirmed that HYFD prevented obesity in mice by enhancing fatty acid catabolism via the activation of the AMPK/PPAR&#x3b1;/CPT1a signaling pathway.<br><br>CONCLUSION: Our results provided novel insights into the mechanism of citrus physiological premature fruit drop and its potential role in preventing obesity, while sparking greater interest in leveraging more biomass waste.}, }
@article {pmid39764653, year = {2024}, author = {Mao, Y and Huang, Y and Zhang, W and Liang, H and Liu, F and Luo, Q and Xu, C and Qin, Y and Liu, J and Tang, S and Liu, H and Ge, X}, title = {FMT reduces systemic inflammatory response in severe acute pancreatitis by increasing the abundance of intestinal Bifidobacteria and fecal bacteria.}, journal = {Biomolecules &amp; biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2024.11445}, pmid = {39764653}, issn = {2831-090X}, abstract = {Severe acute pancreatitis (SAP) is one of the leading causes of hospital admissions for gastrointestinal diseases, with a rising incidence worldwide. Intestinal microbiota dysbiosis caused by SAP exacerbates systemic inflammatory response syndrome and organ dysfunction. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic option for gastrointestinal diseases. In this study, fecal samples from healthy, control, and FMT-treated groups were analyzed using 16S rRNA sequencing to assess microbiome abundance and diversity. Composition and functional prediction analyses were conducted to explore the mechanisms underlying FMT in SAP. FMT significantly improved clinical parameters in SAP patients, including leukocyte count, C-reactive protein (CRP), neutrophil granulocyte count, lactate dehydrogenase (LDH), and calcitonin (P < 0.05). Organ failure rates significantly increased in the control group but decreased in the FMT group after treatment (P < 0.05). Fecal microbiota sequencing revealed that FMT significantly upregulated the abundance of Bifidobacterium longum among all SAP patients (P < 0.05). Receiver operating characteristic (ROC) curve analysis indicated that Bifidobacterium longum might play a critical role in the efficacy of FMT, with an area under the curve (AUC) value of 0.84. Additionally, there was a negative correlation between Bifidobacterium longum abundance and procalcitonin (PCT) levels, as well as a negative correlation between Escherichia coli abundance and both CT and Ca values (P < 0.05). The relative abundances of Bifidobacterium longum and Escherichia coli were significantly higher in the FMT group compared to the Bifidobacterium triple viable group (P < 0.05). In conclusion, this research supports FMT as a safe and effective intervention for treating SAP patients.}, }
@article {pmid39764615, year = {2025}, author = {Harris, SC and Bajaj, JS}, title = {Interaction of the Gut-Liver-Brain Axis and the sterolbiome with sexual dysfunction in patients with cirrhosis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446390}, doi = {10.1080/19490976.2024.2446390}, pmid = {39764615}, issn = {1949-0984}, mesh = {Humans ; *Liver Cirrhosis/complications/metabolism ; *Gastrointestinal Microbiome ; *Brain-Gut Axis/physiology ; *Sexual Dysfunction, Physiological/metabolism/etiology/physiopathology ; *Liver/metabolism ; Sterols/metabolism ; Brain/metabolism ; Gonadal Steroid Hormones/metabolism ; Animals ; Quality of Life ; }, abstract = {There is a complex interplay between the gut microbes, liver, and central nervous system, a gut-liver-brain axis, where the brain impacts intestinal and hepatic function while the gut and liver can impact cognition and mental status. Dysregulation of this axis can be seen in numerous diseases. Hepatic encephalopathy, a consequence of cirrhosis, is perhaps the best studied perturbation of this system. However, patients with cirrhosis have been shown to have increased incidence of other disorders of mental health which may be otherwise less clinically identifiable. Sexual dysfunction affects a large proportion of patients with cirrhosis and is associated with decreased quality of life. Screening for sexual dysfunction in patients with cirrhosis is often overlooked, and even when identified, treatment options are limited, particularly in patients with advanced liver disease. The mechanism by which patients with cirrhosis develop sexual dysfunction is multifactorial, but a key driver of this clinical manifestation is alterations in circulating sex hormones. In patients with cirrhosis, low serum sex hormones have been shown to be associated with higher mortality regardless of MELD score. The gut microbiome has been shown to have an immense metabolic capacity to metabolize steroid hormones. This "sterolbiome" has already been implicated in other disease processes and has been linked to low circulating sex hormones, suggesting a new mechanism by which sex hormones may be altered in disease states where the gut-liver-brain axis is disrupted. The aim of this review is to cover sex hormone changes and sexual dysfunction in cirrhosis, examine the gut microbiome and its metabolic capacity, particularly for steroid hormones, and consider how microbial changes using fecal microbiota transplant could modulate sexual dysfunction.}, }
@article {pmid39764447, year = {2024}, author = {Wang, J and Zhuang, P and Lin, B and Zheng, J and Li, H and Tang, W and Ye, W and Chen, X and Zheng, M}, title = {Comparative analysis of gut microbiota in metabolic syndrome and obese children from Southeastern China.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1503302}, pmid = {39764447}, issn = {1664-302X}, abstract = {The prevalence of childhood obesity is rising globally, with some obese children progressing to develop metabolic syndrome (MS). However, the specific differences between these groups remain unclear. To investigate the differences in gut microbiota, we conducted physiological and biochemical assessments, alongside 16S rRNA sequencing, in a cohort of 32 children from Southeastern China, which included 4 normal-weight children, 5 with mild obesity, 9 with moderate obesity, 9 with severe obesity, and 5 with metabolic syndrome. Our results indicated that waist circumference, serum triglycerides, total cholesterol, non-HDL levels, and the prevalence of fatty liver were significantly elevated in both obese and MS children compared to their normal-weight peers, with the MS group exhibiting more pronounced abnormalities. Conversely, HDL levels showed a contrasting trend. Additionally, alpha diversity of gut microbiota increased with weight, while beta diversity analysis revealed significant compositional differences between children with MS and those who were normal weight or obese. At the class and genus levels, we found that the relative abundance of c_Gammaproteobacteria increased with weight, whereas c_Bacteroidia and g_Bacteroides decreased. Notably, g_Faecalibacterium was significantly less abundant in the MS group compared to the other cohorts. LEfSe and functional analyses identified distinct gut microbiota and functional differences between children with MS and those with normal weight or obesity. Furthermore, gavage experiments in mice showed that gut microbiota from obese and MS subjects significantly increased serum triglycerides and cholesterol levels, leading to hepatocellular damage. In contrast, fecal gavage from normal-weight individuals into obese model mice significantly reduced serum triglycerides and the number of degenerative liver cells, as well as the extent of fat accumulation. These findings provide critical insights into the understanding and management of obesity and metabolic syndrome in pediatric populations.}, }
@article {pmid39762283, year = {2025}, author = {Feng, C and Wu, Y and Zhang, X and Wang, S and Wang, J and Yang, H}, title = {Maternal milk fat globule membrane enriched gut L. murinus and circulating SCFAs to improve placental efficiency and fetal development in intrauterine growth restricted mice model.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2449095}, doi = {10.1080/19490976.2024.2449095}, pmid = {39762283}, issn = {1949-0984}, mesh = {Animals ; Female ; Pregnancy ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Placenta/metabolism ; *Fetal Growth Retardation/metabolism ; *Glycoproteins/metabolism ; *Fatty Acids, Volatile/metabolism ; *Lipid Droplets/metabolism ; *Glycolipids/metabolism ; *Fetal Development/drug effects ; *Disease Models, Animal ; Lactobacillus ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; }, abstract = {Intrauterine growth restriction (IUGR) caused by placental dysfunctions leads to fetal growth defects. Maternal microbiome and its metabolites have been reported to promote placental development. Milk fat globule membrane (MFGM) is known for its diverse bioactive functions, while the effects of gestational MFGM supplementation on the maternal gut microbiota, placental efficiency, and fetal development remained unclear. In this study, low protein diet-induced IUGR decreased the litter birth weight, fetal birth weight, and the fetal/placental ratio in pregnant mice, while gestational MFGM supplementation restored these impairments. Meanwhile, MFGM supplementation during gestation enriched intestinal Lactobacillus murinus (L. murinus) and increased luminal and circulating short chain fatty acids (SCFAs) in IUGR pregnant mice, which improved placental efficiency and fetal development due to an enhanced antioxidant capacity and a decreased inflammation. In addition, fecal microbiota transplantation (FMT) with MFGM-derived microbiota reprinted the promoted phenotypes of maternal litter characteristics, gut L. murinus enrichment, placental efficiency, and fetal gut development in MFGM-fed pregnant mice, which were also recapitulated by exogenous administration with L. murinus or SCFAs cocktail. Mechanically, MFGM, MFGM-derived microbiota, L. murinus, or SCFAs cocktail activated IUGR-induced depressive phosphorylation of PI3K-Akt signaling in the placenta. Moreover, in vitro placental cells cultivation under amino acid shortage model (AAS) or oxygen-glucose shortage model (OGS) was used to validate that MFGM-derived key microbial and circulating SCFAs cocktails can alleviate placental oxidative stress and inflammation via activating PI3K/Akt signaling. Taken together, gestational MFGM supplementation enriched intestinal L. murinus and circulating SCFAs of IUGR pregnant mice, thereby improving placental efficiency, fetal growth, and intestinal functions of IUGR fetus. Our findings will provide theoretical support for the application of MFGM in the maternal-placental-fetal nutrition to address pregnancy malnutrition-induced IUGR.}, }
@article {pmid39762111, year = {2025}, author = {Al-Shakhshir, S and Quraishi, MN and Mullish, B and Patel, A and Vince, A and Rowe, A and Homer, V and Jackson, N and Gyimah, D and Shabir, S and Manzoor, S and Cooney, R and Alrubaiy, L and Quince, C and van Schaik, W and Hares, M and Beggs, AD and Efstathiou, E and Rimmer, P and Weston, C and Iqbal, T and Trivedi, PJ}, title = {FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e095392}, pmid = {39762111}, issn = {2044-6055}, mesh = {Adult ; Female ; Humans ; Male ; *Cholangitis, Sclerosing/therapy ; Clinical Trials, Phase II as Topic ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/therapy/microbiology ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity. However, the longevity of such changes and the impact on markers of disease activity and disease progression have not been studied. The aim of this clinical trial is to determine the effects of repeated FMT as a treatment for PSC-IBD.<br><br>METHODS AND ANALYSIS: FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO) is a phase IIa randomised placebo-controlled trial to assess the efficacy and safety of repeated colonic administration of FMT in patients with non-cirrhotic PSC-IBD. Fifty-eight patients will be recruited from six sites across England and randomised in a 1:1 ratio between active FMT or FMT placebo arms. FMT will be manufactured by the University of Birmingham Microbiome Treatment Centre, using stool collected from rigorously screened healthy donors. A total of 8&#x2009;weekly treatments will be delivered; the first through colonoscopic administration (week 1) and the remaining seven via once-weekly enema (up to week 8). Participants will then be followed on a 12-weekly basis until week 48 from the first treatment visit. The primary efficacy outcome will be to determine the effect of FMT on serum alkaline phosphatase values over time (end of study at 48 weeks). Key secondary outcomes will be to evaluate the impact of FMT on other liver biochemical parameters, PSC risk scores, circulating and imaging markers of liver fibrosis, health-related quality of life measures, IBD activity and the incidence of PSC-related clinical events. Key translational objectives will be to identify mucosal metagenomic, metatranscriptomic, metabolomic and immunological pathways associated with the administration of FMT.<br><br>ETHICS AND DISSEMINATION: The protocol was approved by the South Central-Hampshire B Research Ethics Committee (REC 23/SC/0147). Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.<br><br>TRIAL REGISTRATION NUMBER: The trial was registered at ClinicalTrials.gov on 23 February 2024 (NCT06286709). Weblink: Study Details | FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis | ClinicalTrials.gov.}, }
@article {pmid39761011, year = {2024}, author = {Jain, V and Dalby, MJ and Alexander, EC and Burford, C and Acford-Palmer, H and Serghiou, IR and Teng, NMY and Kiu, R and Gerasimidis, K and Zafeiropoulou, K and Logan, M and Verma, A and Davenport, M and Hall, LJ and Dhawan, A}, title = {Association of gut microbiota and gut metabolites and adverse outcomes in biliary atresia: A longitudinal prospective study.}, journal = {Hepatology communications}, volume = {8}, number = {11}, pages = {}, pmid = {39761011}, issn = {2471-254X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Biliary Atresia/surgery/microbiology/metabolism ; *Feces/microbiology ; Male ; Female ; Prospective Studies ; Infant ; Longitudinal Studies ; Portoenterostomy, Hepatic ; RNA, Ribosomal, 16S/genetics ; Enterococcus ; Case-Control Studies ; Infant, Newborn ; Bifidobacterium/isolation &amp; purification ; }, abstract = {BACKGROUND: The Kasai portoenterostomy (KPE) aims to re-establish bile flow in biliary atresia (BA); however, BA remains the commonest indication for liver transplantation in pediatrics. Gut microbiota-host interplay is increasingly associated with outcomes in chronic liver disease. This study characterized fecal microbiota and fatty acid metabolites in BA.<br><br>METHODS: Fecal samples were prospectively collected in newly diagnosed BA infants (n = 55) before and after KPE. Age-matched healthy control (n = 19) and cholestatic control (n = 21) fecal samples were collected. Fecal 16S rRNA gene amplicon sequencing for gut microbiota and gas chromatography for fecal fatty acids was performed.<br><br>RESULTS: Increased abundance of Enterococcus in pre-KPE BA and cholestatic control infants, compared to healthy infants, was demonstrated. At the early post-KPE time points, increased alpha diversity was revealed in BA versus healthy cohorts. A lower relative abundance of Bifidobacterium and increased Enterococcus, Clostridium, Fusobacterium, and Pseudomonas was seen in infants with BA. Fecal acetate was reduced, and fecal butyrate and propionate were elevated in early post-KPE BA infants. Higher post-KPE alpha diversity was associated with nonfavorable clinical outcomes (6-month jaundice and liver transplantation). A higher relative abundance of post-KPE Streptococcus and Fusobacterium and a lower relative abundance of Dorea, Blautia, and Oscillospira were associated with nonfavorable clinical outcomes. Blautia inversely correlated to liver disease severity, and Bifidobacterium inversely correlated to fibrosis biomarkers. Bifidobacterium abundance was significantly lower in infants experiencing cholangitis within 6 months after KPE.<br><br>CONCLUSIONS: Increased diversity, enrichment of pathogenic, and depletion of beneficial microbiota early post-KPE are all factors associated with nonfavorable BA outcomes. Manipulation of gut microbiota in the early postsurgical period could provide therapeutic potential.}, }
@article {pmid39760535, year = {2025}, author = {Saha, S and Schnabl, B}, title = {Modulating the microbiome in chronic liver diseases - current evidence on the role of fecal microbiota transplantation.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {19}, number = {1}, pages = {53-64}, pmid = {39760535}, issn = {1747-4132}, support = {I01 BX004594/BX/BLRD VA/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; R21 AA031410/AA/NIAAA NIH HHS/United States ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; *Liver Diseases/therapy/microbiology ; Chronic Disease ; Treatment Outcome ; Clostridium Infections/therapy/microbiology ; }, abstract = {INTRODUCTION: The gut microbiota has a complex relationship with the human host and is key to maintaining health. Disruption of the healthy diverse gut microbial milieu plays an important role in the pathogenesis of several diseases including Clostridioides difficile infection (CDI), inflammatory bowel disease, irritable bowel syndrome, alcohol-related liver disease and metabolic-dysfunction associated steatotic liver disease (MASLD). Fecal microbiota transplantation (FMT) is highly effective in treating CDI, though its utility in other diseases is still being explored.<br><br>AREAS COVERED: In this narrative review, we explore the role of gut microbiota in liver diseases, focusing on key changes in the microbial composition and function. We summarize current evidence on the role of FMT, identifying gaps in current research and outlining future directions for investigation. We comprehensively searched PubMed through 15 October 2024 to identify relevant studies.<br><br>EXPERT OPINION: While data from available studies shows promise, more research is necessary before we can use FMT for liver diseases. Key areas that require further study are - determining the optimal FMT regimen for each disease, establishing efficacy and safety with larger clinical trials, ensuring safe and equitable access to the FMT product and mechanistic insights into the reasons for success or failure of FMT.}, }
@article {pmid39759692, year = {2024}, author = {Muzaffer, M and Masarath, A and Mohammed, F}, title = {Biliary Atresia: A Case Report.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e75087}, pmid = {39759692}, issn = {2168-8184}, abstract = {Biliary atresia (BA) is a serious hepatobiliary disorder that occurs due to progressive inflammation and scarring obstruction in the bile ducts, posing a threat to life. This condition usually appears in infants, and timely identification is fundamental for a better prognosis. If left untreated, individuals will inevitably experience liver damage and mortality. This case report describes a nine-month-old female infant presenting with jaundice, icteric sclera, yellowish skin, acholic feces, and hepatomegaly. Elevated liver enzymes and a hepatobiliary iminodiacetic acid (HIDA) scan confirmed BA. Histopathological examination revealed fibrosis, cholestatic disease, and an atretic gallbladder. A modified Kasai portoenterostomy (KPE) with Roux-en-Y jejunojejunostomy was performed, and the infant was discharged with supportive care. However, seven months post-Kasai portoenterostomy, the infant presented with persistent jaundice and progressive deterioration of liver function, indicative of a failed Kasai procedure. Consequently, she was scheduled to undergo liver transplantation (LT) as a definitive treatment. BA is a rare disorder that is observed across nearly all ethnic groups, though the incidence rates vary significantly. This case highlights the efficacy of liver transplantation in treating failed Kasai procedures and demonstrates the potential for enhanced outcomes in infants with end-stage liver disease.}, }
@article {pmid39758967, year = {2025}, author = {Thorndal, C and Kragsnaes, MS and Nilsson, AC and Holm, DK and dePont Christensen, R and Ellingsen, T and Kjeldsen, J and Bjørsum-Meyer, T}, title = {Safety and efficacy of faecal microbiota transplantation in patients with acute uncomplicated diverticulitis: study protocol for a randomised placebo-controlled trial.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848241309868}, pmid = {39758967}, issn = {1756-283X}, abstract = {BACKGROUND: Little is known about the involvement of gut microbiota in the disease course of diverticulitis and the potential benefits of manipulating the gut milieu. We propose to conduct a randomised placebo-controlled feasibility trial of faecal microbiota transplantation (FMT) given as capsules to patients with acute uncomplicated diverticulitis.<br><br>OBJECTIVES: The objective is primarily to investigate the feasibility of clinical safety, explore efficacy associated with FMT in this patient population, and examine changes in patient-reported quality of life and the composition and function of the gut microbiota.<br><br>DESIGN: Study protocol for a randomised placebo-controlled trial.<br><br>METHODS AND ANALYSIS: Participants with acute, uncomplicated diverticulitis, as confirmed by computed tomography (CT) scan, will be recruited from Odense University Hospital (Denmark) and randomly assigned to either the intervention group or the control group. The intervention group will consist of 20 patients who receive encapsulated FMT. The control group will also consist of 20 patients, receiving placebo capsules. Primary safety endpoint: Patient safety is monitored by (a) the number of re-admissions and (b) the number of adverse events within 3&#x2009;months of FMT/placebo; Primary efficacy endpoint: Reduction in the proportion of patients treated with antibiotics within 3&#x2009;months following FMT/placebo; Secondary outcome: Change from baseline to 3&#x2009;months in the GI-QLI questionnaire. Results will be analysed using an intention-to-treat approach. Adverse events or unintended consequences will be reported.<br><br>ETHICS AND DISCUSSION: This is the first study to investigate the safety and efficacy of FMT in patients with acute uncomplicated diverticulitis. The project has the potential to broaden the knowledge and literature on the role of the intestinal microbiota in diverticulitis, and we believe it will elevate our understanding of cause and effect.<br><br>TRIAL REGISTRATION: Informed consent is obtained from all participants. The study is approved by the regional ethics committee (ref. S-20230023) and the Danish Data Protection Agency (ref. 24/2435). The trial was registered on clinicaltrials.gov (NCT06254625) on 10th February 2024.}, }
@article {pmid39758313, year = {2024}, author = {Liu, B and Zhang, Z and Zhao, J and Li, X and Wang, Y and Liu, L and Qiao, W and Chen, L}, title = {Lactiplantibacillus plantarum HM-P2 influences gestational gut microbiome and microbial metabolism.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1489359}, pmid = {39758313}, issn = {2296-861X}, abstract = {INTRODUCTION: Human milk-derived probiotics are beneficial bacteria that provide gestational health benefits, for both pregnant women and their offspring. The study aims to investigate whether the administration of human milk-derived probiotic L. plantarum HM-P2 could effectively influence gestational health.<br><br>METHODS: The gestational humanized microbiome model was built by fecal microbiome transplant from gestational women into germ-free (GF) mice.<br><br>RESULTS: HM-P2 was successfully planted and increased the top crypt depth of the colon, and microbes such as L. reuteri, Anaerofilum sp. An201, and Gemmiger were up-regulated in the HM-P2 group throughout gestation. HM-P2 significantly promoted the contents of intestinal caproic acid, bile acids, and tryptophan catabolites such as serotonin. Gut microbes were associated with these bile acids and tryptophans.<br><br>DISCUSSION: HM-P2 could modulate the microbial community and microbial metabolites in gestational humanized GF mice. This probiotic strain could be a potential gestational dietary supplement with health benefits.}, }
@article {pmid39757809, year = {2025}, author = {Huang, ST and Hu, YH and Gao, YC and Zhou, DD and Chen, MY and Wang, L and Song, JY and Zhou, HH and Zhang, W and Huang, WH}, title = {Hypoglycemic Effect of Ginsenoside Compound K Mediated by N-Acetylserotonin Derived From Gut Microbiota.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.8385}, pmid = {39757809}, issn = {1099-1573}, support = {82074000//National Natural Science Foundation of China/ ; 82073945//National Natural Science Foundation of China/ ; 81874329//National Natural Science Foundation of China/ ; 2023YFC3405200//National Key Research and Development Program of China/ ; 2021YFA1301200//National Key Research and Development Program of China/ ; 2024JJ5585//Hunan Provincial Natural Science Foundation of China/ ; 2023SK2083//Scientific Research Project of Furong Laboratory of Central South University/ ; }, abstract = {Ginsenoside compound K (GCK) has been proved to have great hypoglycemic effect pertinent to gut microbiota. However, the improvement of high-fat-diet (HFD)-induced type 2 diabetes (T2D) as well as the mechanism of GCK mediated by gut microbiota is not well-known. This study aimed to investigate the hypoglycemic effects and mechanism of GCK on a HFD-induced diabetic mouse model. HFD-induced pseudo-germ free (GF) T2D mice model and fecal microbiota transplantation (FMT) experiments were performed to clarify the role of gut microbiota in the hypoglycemic effect of GCK. Differential metabolites were screened by untargeted metabolomics analysis and their functions were verified by suppling to T2D mice. The level of glucagon-like peptide-1 (GLP-1) in plasma was detected by ELISA analysis to explore the potential hypoglycemic mechanism of GCK. The results showed GCK alleviated metabolic disorders and altered gut microbiota in HFD-induced diabetic mice, which was transmitted to pseudo-GF diabetic mice via FMT experiment to reproduce the hypoglycemic effect. Non-targeted metabolites analysis on cecal content samples indicated that N-acetylserotonin (NAS) was markedly increased after GCK treatment. Moreover, gavage with NAS improved insulin sensitivity and increased the secretion of GLP-1 in HFD mice. Our study showed that GCK had hypoglycemic effect through modifying gut microbiota profiling.}, }
@article {pmid39757609, year = {2024}, author = {Bhat, MM and Hussain, MS and Bisht, AS and Agrawal, M and Sultana, A and Khurrana, N and Kumar, R}, title = {Frontiers in Pulmonary Hypertension: A Comprehensive Insight of Etiological Advances.}, journal = {Current reviews in clinical and experimental pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724328325178241210174545}, pmid = {39757609}, issn = {2772-4336}, abstract = {Pulmonary hypertension (PH) is a severe, progressive disorder characterized by elevated pulmonary arterial pressure, leading to right ventricular failure and increased mortality. Despite advancements in management, the median survival for PH patients remains 5-7 years, with an inhospital mortality rate of approximately 6%. The core pathological feature of PH is pulmonary vascular remodeling (PVR), a multifactorial process involving endothelial dysfunction, inflammation, and aberrant immune responses. While current therapies target endothelial dysfunction, they fall short of preventing PVR or halting disease progression. Emerging research highlights the potential of immune-inflammatory pathways, oxygen-sensing mechanisms, and gut microbiota modulation as therapeutic targets. Integrating nutritional strategies, probiotics, and fecal microbiota transplantation (FMT) as adjunctive therapies also shows promise. These factors may collectively influence PVR, offering novel insights into therapeutic avenues for PH management in the future.}, }
@article {pmid39756658, year = {2025}, author = {Chen, Q and Liu, F and Zhang, G and Qu, Q and Chen, Y and Li, M and Huang, Q and Fu, H and Zhu, X and He, Y and Huang, X and Zhang, X}, title = {Progesterone regulates gut microbiota mediating bone marrow mesenchymal stem cell injury in immune thrombocytopenia patients during pregnancy.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {23}, number = {4}, pages = {1428-1441}, doi = {10.1016/j.jtha.2024.12.027}, pmid = {39756658}, issn = {1538-7836}, mesh = {Female ; Animals ; *Mesenchymal Stem Cells/metabolism/pathology/drug effects ; *Gastrointestinal Microbiome/drug effects ; Pregnancy ; Humans ; *Progesterone/metabolism/pharmacology ; *Purpura, Thrombocytopenic, Idiopathic/microbiology/blood/immunology ; Metabolomics ; Adult ; Apoptosis ; Mice ; Disease Models, Animal ; Cells, Cultured ; *Pregnancy Complications/blood/microbiology ; Case-Control Studies ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Immune thrombocytopenia during pregnancy (PITP) is the most common cause of platelet reduction in early and mid-pregnancy. However, the pathogenesis of PITP is still unclear.<br><br>OBJECTIVES: To determine the characteristics of bone marrow mesenchymal stem cells (BM-MSCs) in PITP patients and to explore the associations between metabolites, the gut microbiota, and BM-MSCs in PITP.<br><br>METHODS: The characteristics of BM-MSCs were detected through in&#xa0;vitro and in&#xa0;vivo experiments. Nontargeted metabolomics was used to screen metabolites. The features of the gut microbiota were analyzed by 16S rDNA sequencing. PITP and fecal microbiota transplantation (FMT) mouse model were established to explore the associations between metabolites, gut microbiota, and BM-MSCs.<br><br>RESULTS: BM-MSCs from PITP patients had significant senescence and apoptosis, as well as impaired immunoregulatory function. Metabolomic analysis indicated that progesterone was the most significant specific metabolite in PITP patients. In&#xa0;vivo studies showed that progesterone mediated MSC injury. Further analysis of the gut microbiota and FMT experiments revealed that progesterone mediated BM-MSCs injury by regulating the composition of the gut microbiota in PITP. RNA sequencing analysis of BM-MSCs from FMT mice revealed abnormal expression of genes related to cell aging and the NOD-like receptor signaling pathway.<br><br>CONCLUSION: In conclusion, BM-MSCs in the PITP were significantly impaired, which was associated with increased progesterone and changes in the gut microbiota regulated by progesterone. Intervening with the gut microbiota may become a new treatment for PITP.}, }
@article {pmid39754054, year = {2025}, author = {Azhar Ud Din, M and Lin, Y and Lyu, C and Yi, C and Fang, A and Mao, F}, title = {Advancing therapeutic strategies for graft-versus-host disease by targeting gut microbiome dynamics in allogeneic hematopoietic stem cell transplantation: current evidence and future directions.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {2}, pmid = {39754054}, issn = {1528-3658}, mesh = {*Graft vs Host Disease/etiology/microbiology ; Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; *Transplantation, Homologous ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Hematopoietic stem cell transplantation (HSCT) is a highly effective therapy for malignant blood illnesses that pose a high risk, as well as diseases that are at risk due to other variables, such as genetics. However, the prevalence of graft-versus-host disease (GVHD) has impeded its widespread use. Ensuring the stability of microbial varieties and associated metabolites is crucial for supporting metabolic processes, preventing pathogen intrusion, and modulating the immune system. Consequently, it significantly affects the overall well-being and susceptibility of the host to disease. Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) may experience a disruption in the balance between the immune system and gut bacteria when treated with medicines and foreign cells. This can lead to secondary intestinal inflammation and GVHD. Thus, GM is both a reliable indicator of post-transplant mortality and a means of enhancing GVHD prevention and treatment after allo-HSCT. This can be achieved through various strategies, including nutritional support, probiotics, selective use of antibiotics, and fecal microbiota transplantation (FMT) to target gut microbes. This review examines research advancements and the practical use of intestinal bacteria in GVHD following allo-HSCT. These findings may offer novel insights into the prevention and treatment of GVHD after allo-HSCT.}, }
@article {pmid39747695, year = {2025}, author = {Wang, X and Fang, Y and Liang, W and Cai, Y and Wong, CC and Wang, J and Wang, N and Lau, HC and Jiao, Y and Zhou, X and Ye, L and Mo, M and Yang, T and Fan, M and Song, L and Zhou, H and Zhao, Q and Chu, ES and Liang, M and Liu, W and Liu, X and Zhang, S and Shang, H and Wei, H and Li, X and Xu, L and Liao, B and Sung, JJY and Kuang, M and Yu, J}, title = {Gut-liver translocation of pathogen Klebsiella pneumoniae promotes hepatocellular carcinoma in mice.}, journal = {Nature microbiology}, volume = {10}, number = {1}, pages = {169-184}, pmid = {39747695}, issn = {2058-5276}, support = {82173191//National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund)/ ; }, mesh = {*Klebsiella pneumoniae/pathogenicity/physiology/genetics ; Animals ; *Carcinoma, Hepatocellular/microbiology/pathology ; *Liver Neoplasms/microbiology/pathology ; Mice ; *Gastrointestinal Microbiome ; Humans ; Toll-Like Receptor 4/metabolism ; *Liver/microbiology/pathology ; *Klebsiella Infections/microbiology/complications ; Fecal Microbiota Transplantation/adverse effects ; *Bacterial Translocation ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Carcinogenesis ; Cell Proliferation ; Feces/microbiology ; }, abstract = {Hepatocellular carcinoma (HCC) is accompanied by an altered gut microbiota but whether the latter contributes to carcinogenesis is unclear. Here we show that faecal microbiota transplantation (FMT) using stool samples from patients with HCC spontaneously initiate liver inflammation, fibrosis and dysplasia in wild-type mice, and accelerate disease progression in a mouse model of HCC. We find that HCC-FMT results in gut barrier injury and translocation of live bacteria to the liver. Metagenomic analyses and bacterial culture of liver tissues reveal enrichment of the gut pathogen Klebsiella pneumoniae in patients with HCC and mice transplanted with the HCC microbiota. Moreover, K. pneumoniae monocolonization recapitulates the effect of HCC-FMT in promoting liver inflammation and hepatocarcinogenesis. Mechanistically, K. pneumoniae surface protein PBP1B interacts with and activates TLR4 on HCC cells, leading to increased cell proliferation and activation of oncogenic signalling. Targeting gut colonization using K. oxytoca or TLR4 inhibition represses K. pneumoniae-induced HCC progression. These findings indicate a role for an altered gut microbiota in hepatocarcinogenesis.}, }
@article {pmid39747680, year = {2025}, author = {Menon, R and Bhattarai, SK and Crossette, E and Prince, AL and Olle, B and Silber, JL and Bucci, V and Faith, J and Norman, JM}, title = {Multi-omic profiling a defined bacterial consortium for treatment of recurrent Clostridioides difficile infection.}, journal = {Nature medicine}, volume = {31}, number = {1}, pages = {223-234}, pmid = {39747680}, issn = {1546-170X}, mesh = {*Clostridium Infections/microbiology/therapy/drug therapy ; Humans ; *Clostridioides difficile/pathogenicity ; Gastrointestinal Microbiome/genetics ; *Fecal Microbiota Transplantation/methods ; Recurrence ; Anti-Bacterial Agents/therapeutic use ; Feces/microbiology ; Male ; Female ; Middle Aged ; Bile Acids and Salts/metabolism ; Adult ; *Microbial Consortia ; Multiomics ; }, abstract = {Donor-derived fecal microbiota treatments are efficacious in preventing recurrent Clostridioides difficile infection (rCDI), but they have inherently variable quality attributes, are difficult to scale and harbor the risk of pathogen transfer. In contrast, VE303 is a defined consortium of eight purified, clonal bacterial strains developed for prevention of rCDI. In the phase 2 CONSORTIUM study, high-dose VE303 was well tolerated and reduced the odds of rCDI by more than 80% compared to placebo. VE303 organisms robustly colonized the gut in the high-dose group and were among the top taxa associated with non-recurrence. Multi-omic modeling identified antibiotic history, baseline stool metabolites and serum cytokines as predictors of both on-study CDI recurrence and VE303 colonization. VE303 potentiated early recovery of the host microbiome and metabolites with increases in short-chain fatty acids, secondary bile acids and bile salt hydrolase genes after antibiotic treatment for CDI, which is considered important to prevent CDI recurrences. These results support the idea that VE303 promotes efficacy in rCDI through multiple mechanisms.}, }
@article {pmid39746875, year = {2025}, author = {Faith, JJ}, title = {Assessing live microbial therapeutic transmission.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447836}, doi = {10.1080/19490976.2024.2447836}, pmid = {39746875}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridium Infections/microbiology/therapy/drug therapy ; *Clostridioides difficile/drug effects/physiology/genetics ; *Gastrointestinal Microbiome ; Feces/microbiology ; Animals ; }, abstract = {The development of fecal microbiota transplantation and defined live biotherapeutic products for the treatment of human disease has been an empirically driven process yielding a notable success of approved drugs for the treatment of recurrent Clostridioides difficile infection. Assessing the potential of this therapeutic modality in other indications with mixed clinical results would benefit from consistent quantitative frameworks to characterize drug potency and composition and to assess the impact of dose and composition on the frequency and duration of strain engraftment. Monitoring these drug properties and engraftment outcomes would help identify minimally sufficient sets of microbial strains to treat disease and provide insights into the intersection between microbial function and host physiology. Broad and correct usage of strain detection methods is essential to this advancement. This article describes strain detection approaches, where they are best applied, what data they require, and clinical trial designs that are best suited to their application.}, }
@article {pmid39746695, year = {2024}, author = {He, H and Zhang, JP and Wei, ZJ and Lu, Y and Zhao, YL and Sun, RJ}, title = {[Role of human herpesvirus infection in refractory gastrointestinal graft-versus-host-disease after hematopoietic stem cell transplantation and the diagnosis and treatment thereof].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {45}, number = {11}, pages = {1016-1021}, pmid = {39746695}, issn = {0253-2727}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; Adult ; Middle Aged ; *Graft vs Host Disease/diagnosis/etiology ; Retrospective Studies ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Herpesviridae Infections/diagnosis ; Transplantation, Homologous ; Cytomegalovirus/isolation &amp; purification ; Herpesvirus 6, Human/isolation &amp; purification ; }, abstract = {Objective: This study aimed to investigate the role of human herpesvirus (HHV) infection in refractory intestinal graft-versus-host disease (GI-GVHD) after hematopoietic stem cell transplantation (HSCT) and its diagnosis and treatment. Methods: This study retrospectively analyzed patients presenting with refractory GI-GVHD after allogeneic HSCT (allo-HSCT) with concomitant colonoscopy and mucosal biopsy at Lu Daopei Hospital, Yanda, Hebei, from March 2022 to July 2024. Human herpesvirus 6 (HHV6), HHV7, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) detection with the RQ-PCR method. The intestinal mucosa was pathologically assessed and immunohistochemistry was utilized to detect the CMV early antigen, CMV late antigen, and EBV by in situ hybridization. Results: This study included 42 patients, consisting of 25 males and 17 females with a median age of 26 (1-59) years. All were histopathologically diagnosed as GI-GVHD. Among them, 34 (81.0%) cases had combined viral enteritis, with 52.4% positive for EBV, 38.1% positive for HHV6, 26.2% positive for CMV, and 14.3% positive for HHV7. Further, 17 (40.5%) cases had mixed viral infections, including 5 EBV+ HHV6, 3 CMV+HHV6, 3 CMV+EBV, 2 CMV+EBV+HHV6, 2 EBV+HHV6+HHV7, 1 EBV+HHV7, and 1 HHV6 + HHV7 cases. Furthermore, 17 (40.5%) had a single viral infection, including 9 EBV, 3 CMV, 3 HHV6, and 2 HHV7 cases. Moreover, 17 (40.5%) patients exhibited a positive histopathological viral test, including 7 (16.6%) CMV-positive and 12 (28.5%) EBV-positive cases. The same positive virus was detected in the feces of all 34 patients with positive tissue homogenate virus, and the positive rate of the same virus in the blood was 17.6%. Tissue homogenized virus testing was utilized as the diagnostic criterion for enterocolitis: blood tests for CMV, EBV, HHV6, and HHV7 demonstrated a sensitivity of 45.4%, 4.5%, 6.3%, and 0%, and specificity of 90.3%, 95%, 100%, and 110%, respectively. Additionally, fecal tests for CMV, EBV, HHV6, and HHV7 demonstrated a sensitivity and specificity of 100%. Treatment based on etiology caused ORR and CR rates for diarrhea of 76.1% (32/42) and 66.6% (28/42), respectively. The median follow-up of 42 patients was 13 (1 - 49) months, and 28 patients survived, with an expected 2-year survival rate of 61.9%. Conclusion: In addition to GVHD itself, intestinal human herpesvirus infection is one of the reasons for the refractory nature of GI-GVHD. Viral testing in blood and tissues reveals significant segregation, and the possibility of comorbid viral enteritis cannot be excluded even if a patient with GI-GVHD tests negative for blood viruses.}, }
@article {pmid39744736, year = {2024}, author = {Jeyaraman, N and Jeyaraman, M and Dhanpal, P and Ramasubramanian, S and Ragavanandam, L and Muthu, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Gut microbiome and orthopaedic health: Bridging the divide between digestion and bone integrity.}, journal = {World journal of orthopedics}, volume = {15}, number = {12}, pages = {1135-1145}, pmid = {39744736}, issn = {2218-5836}, abstract = {The gut microbiome, a complex ecosystem of microorganisms in the digestive tract, has emerged as a critical factor in human health, influencing metabolic, immune, and neurological functions. This review explores the connection between the gut microbiome and orthopedic health, examining how gut microbes impact bone density, joint integrity, and skeletal health. It highlights mechanisms linking gut dysbiosis to inflammation in conditions such as rheumatoid arthritis and osteoarthritis, suggesting microbiome modulation as a potential therapeutic strategy. Key findings include the microbiome's role in bone metabolism through hormone regulation and production of short-chain fatty acids, crucial for mineral absorption. The review also considers the effects of diet, probiotics, and fecal microbiota transplantation on gut microbiome composition and their implications for orthopedic health. While promising, challenges in translating microbiome research into clinical practice persist, necessitating further exploration and ethical consideration of microbiome-based therapies. This interdisciplinary research aims to link digestive health with musculoskeletal integrity, offering new insights into the prevention and management of bone and joint diseases.}, }
@article {pmid39744230, year = {2025}, author = {Singh, A and Chandrasekar, SV and Valappil, VT and Scaria, J and Ranjan, A}, title = {Tumor immunomodulation by nanoparticle and focused ultrasound alters gut microbiome in a sexually dimorphic manner.}, journal = {Theranostics}, volume = {15}, number = {1}, pages = {216-232}, pmid = {39744230}, issn = {1838-7640}, mesh = {Animals ; Female ; Male ; *Gastrointestinal Microbiome/immunology ; Mice ; *Nanoparticles/administration &amp; dosage ; *Immunomodulation ; Calreticulin/metabolism ; Cell Line, Tumor ; Immunogenic Cell Death/drug effects ; Mice, Inbred C57BL ; Mouth Neoplasms/immunology/microbiology/therapy ; Sex Characteristics ; Cytokines/metabolism ; }, abstract = {Background: Local immunomodulation with nanoparticles (NPs) and focused ultrasound (FUS) is recognized for triggering anti-tumor immunity. However, the impact of these tumor immunomodulations on sex-specific microbiome diversity at distant sites and their correlation with therapeutic effectiveness remains unknown. Here, we conducted local intratumoral therapy using immunogenic cell death-enhancing Calreticulin-Nanoparticles (CRT-NPs) and FUS in male and female mice. We identified immune-related microbiome populations, aiming to translate our findings into clinical applications. Methods: CRT-NPs were synthesized by loading CRT-delivering plasmids into cationic liposomes. Local tumor therapy was performed using CRT-NP and FUS-based histotripsy (HT) on poorly immunogenic Mouse Oral Squamous Cell Carcinoma (MOC2) in the flank regions of male and female mice. Fecal samples were collected and analyzed before and three weeks post-treatment. The microbiome features were then correlated with immune cell dynamics within tumors and systemic cytokine responses to identify prognostic biomarkers in both male and female subjects. Results: Intratumorally administered CRT-NP induced tumor remission and immune cell activation in both male and female mice, whereas HT was ineffective in males and showed efficacy only in females. Turicibacter and Peptococcus inversely correlated with tumor growth, while Enterorhabdus, Subdologranulum, Desulfovibrio, and Aldercreutzia-Asaccharobacter showed direct correlations with tumor growth. HT induced higher levels of Turicibacter in MOC2-bearing females, while males displayed increased Enterorhabdus and Streptococcus populations. Independent of sex, treatments promoting CD4+ T helper cells, functional CD8+ T cells, and total macrophage infiltration correlated with higher levels of Gastrophilales, Romboutsia, Turicibacter, and Peptococcus. Alternatively, Enterorhabdus, Desulfovibrio, Streptococcus, and Staphylococcus corresponded to poor treatment outcomes in both sexes. Conclusion: An enhanced abundance of Enterorhabdus, Desulfovibrio, Streptococcus, and Staphylococcus in response to immunomodulatory therapies could serve as predictive biomarkers in a sex-independent manner. These findings could also be potentially extended to the realm of personalized interventions through fecal transplantations to reverse immunosuppressive phenotypes in males and improve patient outcomes.}, }
@article {pmid39741383, year = {2025}, author = {van Rheenen, PF and Kolho, KL and Russell, RK and Aloi, M and Deganello, A and Hussey, S and Junge, N and De Laffolie, J and Deneau, MR and Fitzpatrick, E and Griffiths, AM and Hojsak, I and Nicastro, E and Nita, A and Pakarinen, M and Ricciuto, A and de Ridder, L and Sonzogni, A and Tenca, A and Samyn, M and Indolfi, G}, title = {Primary sclerosing cholangitis in children with inflammatory bowel disease: An ESPGHAN position paper from the Hepatology Committee and the IBD Porto group.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {80}, number = {2}, pages = {374-393}, pmid = {39741383}, issn = {1536-4801}, support = {//European Society for Paediatric Gastroenterology Hepatology and Nutrition/ ; }, mesh = {Humans ; *Cholangitis, Sclerosing/diagnosis/therapy/complications/etiology ; *Inflammatory Bowel Diseases/complications ; Child ; Gastroenterology ; Cholangiopancreatography, Magnetic Resonance ; Adolescent ; }, abstract = {OBJECTIVE: We aimed to provide an evidence-supported approach to diagnose, monitor, and treat children with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC).<br><br>METHODS: The core group formulated seven PICO-structured clinical questions. A systematic literature search from inception to December 2022 was conducted by a medical librarian using MEDLINE and EMBASE. Core messages from the literature were phrased as position statements and then circulated to a sounding board composed of international experts in pediatric gastroenterology and hepatology, histopathology, adult gastroenterology and hepatology, radiology, and surgery. Statements reaching at least 80% agreement were considered as final. The other statements were refined and then subjected to a second online vote or rejection.<br><br>RESULTS: Regular screening for gamma-glutamyltransferase (GGT) is essential for detecting possible biliary disease in children with IBD. MR cholangiopancreatography is the radiological modality of choice for establishing the diagnosis of PSC. Liver biopsy is relevant in the evaluation of small duct PSC or autoimmune hepatitis. Children who do not have known IBD at the time of PSC diagnosis should undergo initial screening with fecal calprotectin for asymptomatic colitis, and then at least once yearly thereafter. Children with a cholestatic liver enzyme profile can be considered for treatment with ursodeoxycholic acid and can continue if there is a meaningful reduction or normalization in GGT. Oral vancomycin may have a beneficial effect on GGT and intestinal inflammation, but judicious use is recommended due to the lack of long-term studies. Children with PSC-IBD combined with convincing features of autoimmune hepatitis may benefit from corticosteroids and antimetabolites.<br><br>CONCLUSIONS: We present state-of-the-art guidance on the diagnostic criteria, follow-up strategies, and therapeutic strategies and point out research gaps in children and adolescents with PSC-IBD.}, }
@article {pmid39739648, year = {2025}, author = {Lei, J and Lv, L and Zhong, L and Xu, F and Su, W and Chen, Y and Wu, Z and He, S and Chen, Y}, title = {The Gut Microbiota Affects Anti-TNF Responsiveness by Activating the NAD[+] Salvage Pathway in Ulcerative Colitis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {8}, pages = {e2413128}, pmid = {39739648}, issn = {2198-3844}, support = {82100548//National Natural Science Foundation of China/ ; CSTB2022NSCQ-MSX0094//Natural Science Foundation of Chongqing Municipality/ ; }, mesh = {*Gastrointestinal Microbiome/physiology/drug effects ; *Colitis, Ulcerative/metabolism/microbiology/drug therapy ; Mice ; Animals ; Humans ; *NAD/metabolism ; *Tumor Necrosis Factor-alpha/antagonists &amp; inhibitors/metabolism ; Male ; Infliximab/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; Female ; *Tumor Necrosis Factor Inhibitors/pharmacology ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Approximately 50% of the patients with ulcerative colitis (UC) are primarily nonresponsive to anti-tumor necrosis factor (TNF) therapy or lose their responsiveness over time. The gut microbiota plays an important role in the resistance of UC to anti-TNF therapy; however, the underlying mechanism remains unknown. Here, it is found that the transplantation of gut fecal microbiota from patients with UC alters the diversity of the gut microbiota in dextran sulfate sodium-induced colitis mice and may affect the therapeutic responsiveness of mice to infliximab. Furthermore, the abundances of Romboutsia and Fusobacterium increase in the tissues of patients with UC who do not respond to anti-TNF therapy. Differentially abundant metabolites are mainly enriched in nicotinate and nicotinamide metabolism in NCM460 cells after Fusobacterium nucleatum infection. Mechanistically, F. nucleatum promotes the nicotinamide adenine dinucleotide (NAD[+]) salvage pathway by upregulating NAMPT expression, which subsequently leads to the activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway and promotes the secretion of inflammatory factors, ultimately inhibiting the therapeutic response to anti-TNF drugs. These findings demonstrate that the gut microbiota can influence the response to anti-TNF therapy in patients with UC and highlight the therapeutic potential of targeting F. nucleatum and its associated pathways for preventing and treating drug resistance in UC.}, }
@article {pmid39738016, year = {2024}, author = {Li, Z and Gu, M and Zaparte, A and Fu, X and Mahen, K and Mrdjen, M and Li, XS and Yang, Z and Ma, J and Thoudam, T and Chandler, K and Hesler, M and Heathers, L and Gorse, K and Van, TT and Wong, D and Gibson, AM and Wang, Z and Taylor, CM and Quijada, P and Makarewich, CA and Hazen, SL and Liangpunsakul, S and Brown, JM and Lefer, DJ and Welsh, DA and Sharp, TE}, title = {Alcohol-induced gut microbial reorganization and associated overproduction of phenylacetylglutamine promotes cardiovascular disease.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {10788}, pmid = {39738016}, issn = {2041-1723}, support = {U24 DK1132746//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; U01 AA026917/AA/NIAAA NIH HHS/United States ; R01 AA029984/AA/NIAAA NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; T32 AR065972/AR/NIAMS NIH HHS/United States ; HL171221//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; P50 AA024333/AA/NIAAA NIH HHS/United States ; NSF 2018936//National Science Foundation (NSF)/ ; R01 HL146098/HL/NHLBI NIH HHS/United States ; UH2 AA026226/AA/NIAAA NIH HHS/United States ; R01 DK120679/DK/NIDDK NIH HHS/United States ; KC2210163//U.S. Department of Defense (United States Department of Defense)/ ; R21 AA027199/AA/NIAAA NIH HHS/United States ; P20 GM103424/GM/NIGMS NIH HHS/United States ; R01 DK130227/DK/NIDDK NIH HHS/United States ; P60 AA009803/AA/NIAAA NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R25 HL145817/HL/NHLBI NIH HHS/United States ; UH3 AA026903/AA/NIAAA NIH HHS/United States ; HL160569//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; T32 HL069766/HL/NHLBI NIH HHS/United States ; R01AA030312//U.S. Department of Health &amp; Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)/ ; R01 HL167831/HL/NHLBI NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; RF1 NS133812/NS/NINDS NIH HHS/United States ; R01 HL151398/HL/NHLBI NIH HHS/United States ; R01 HL146514/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Male ; *Glutamine/metabolism/analogs &amp; derivatives ; *Cardiovascular Diseases/metabolism/microbiology/etiology ; Mice ; Humans ; Mice, Inbred C57BL ; Myocytes, Cardiac/metabolism/drug effects ; Ethanol/pharmacology/metabolism ; Oxidative Stress/drug effects ; Fecal Microbiota Transplantation ; Alcoholism/metabolism ; Disease Models, Animal ; Female ; Glutamates/metabolism ; Endothelial Cells/metabolism/drug effects ; Middle Aged ; }, abstract = {The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology. Fecal microbiota transplantation from pair-/alcohol-fed mice into naïve male mice demonstrates the transmissibility of PAGln production and the CVD phenotype. Independent of alcohol exposure, pharmacological-mediated increases in PAGln elicits direct cardiac and vascular dysfunction. PAGln induced hypercontractility and altered calcium cycling in isolated cardiomyocytes providing evidence of improper relaxation which corresponds to elevated filling pressures observed in vivo. Furthermore, PAGln directly induces vascular endothelial cell activation through induction of oxidative stress leading to endothelial cell dysfunction. We thus reveal that the alcohol-induced microbial reorganization and resultant GMM elevation, specifically PAGln, directly contributes to CVD.}, }
@article {pmid39736988, year = {2024}, author = {Wang, F and Wang, Z and Qu, L}, title = {The changes of intestinal flora and metabolites in atopic dermatitis mice.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1462491}, pmid = {39736988}, issn = {1664-302X}, abstract = {INTRODUCTION: Atopic dermatitis (AD) is an allergic disease caused by various factors that can affect an individual's appearance and cause psychological stress. Therefore, it is necessary to investigate the underlying mechanisms and develop effective treatment strategies. The gut microbiota and bacterial metabolism play crucial roles in human diseases. However, their specific role in AD remains unclear.<br><br>METHODS: In this study, we established a mouse model of AD and found that 2,4-dinitrofluorobenzene disrupted the skin barrier in mice. The species composition of intestinal bacteria was then analyzed by fecal 16s rRNA sequencing. The metabolic level of mice was analyzed by untargeted and targeted metabolomics in stool.<br><br>RESULTS: The levels of filaggrin and aquaporin 3 proteins in the model mice and total superoxide dismutase, catalase and malondialdehyde levels were significantly altered. Additionally, inflammatory factors such as tumor necrosis factor-alpha showed a significant increase. Using 16S rRNA gene sequencing, we identified 270 bacterial species with altered abundances of Ruminococcaceae and Bifidobacteriaceae. The untargeted metabolomic analysis detected 1,299 metabolites. Targeted analysis of free fatty acids revealed 49 metabolites with notable increases in linoleic and linolenic acid levels. Fecal bacterial transplantation experiments have demonstrated that oxidative stress, inflammation, and skin barrier damage were alleviated after transplantation.<br><br>DISCUSSION: These findings suggested that the metabolite linoleic acid negatively correlated with Ruminococcaceae and Bifidobacteriaceae may influence AD development. Perturbations in the intestinal bacteria and flora contributed to the development of AD, and the mouse model could serve as a valuable tool for further investigation of therapeutic approaches for managing ADS.}, }
@article {pmid39736924, year = {2025}, author = {Yuan, C}, title = {Molecular mechanisms and therapeutic strategies of gut microbiota modulation in Sarcopenia (Review).}, journal = {Oncology letters}, volume = {29}, number = {3}, pages = {104}, pmid = {39736924}, issn = {1792-1082}, abstract = {Sarcopenia is an age-related disease that is characterized by a decline in muscle mass and function with significant epidemiological and clinical implications. In recent years, gut microbiota has gained attention as an important regulatory factor in human health. To the best of our knowledge, this is the first study to introduce the definition and epidemiological background of sarcopenia and analyze the potential impact of the gut microbiota on muscle metabolism and growth, including aspects such as gut microbiota metabolites, muscle protein synthesis and energy metabolism. Additionally, this article summarizes the current research progress in gut microbiota interventions for the treatment of sarcopenia, such as probiotics, prebiotics and fecal microbiota transplantation and discusses future research directions and potential therapeutic strategies.}, }
@article {pmid39736240, year = {2025}, author = {Qiu, M and Geng, H and Zou, C and Zhao, X and Zhao, C and Xie, J and Wang, J and Zhang, N and Hu, Y and Fu, Y and Wang, J and Hu, X}, title = {Intestinal inflammation exacerbates endometritis through succinate production by gut microbiota and SUCNR1-mediated proinflammatory response.}, journal = {International immunopharmacology}, volume = {146}, number = {}, pages = {113919}, doi = {10.1016/j.intimp.2024.113919}, pmid = {39736240}, issn = {1878-1705}, mesh = {Animals ; Female ; *Gastrointestinal Microbiome/immunology ; *Endometritis/immunology/metabolism/chemically induced/microbiology ; *Succinic Acid/metabolism ; Mice ; Lipopolysaccharides/immunology ; *Receptors, G-Protein-Coupled/metabolism ; Mice, Inbred C57BL ; Dysbiosis ; Dextran Sulfate ; Uterus/metabolism ; Fecal Microbiota Transplantation ; Inflammation ; Humans ; Disease Models, Animal ; }, abstract = {Endometritis poses higher health risks to women. Clinical practice has found that gastrointestinal dysfunction is more likely to lead to the occurrence of endometritis. However, the mechanism is unclear. This study explored the influence and mechanism of DSS-induced intestinal inflammation on endometritis. Our findings demonstrate that DSS-induced intestinal inflammation can worsen LPS-induced endometritis in mice, and this effect is dependent on the gut microbiota, as depleting the gut microbiota eliminates this protective effect. Similarly, FMT from DSS-treated mice to recipient mice exacerbates LPS-induced endometritis. In addition, treatment of DSS disrupted an imbalance of succinate-producing and succinate-consuming bacteria and increased the levels of succinate in the gut and uterine tissues. Furthermore, treatment with succinate aggravates LPS-induced endometritis by activating the succinate receptor 1 (SUCNR1), evidenced by inhibition of the activation of SUCNR1 reversed the inflammatory response in uterine tissues induced by succinate during endometritis induced by LPS. Collectively, the results suggested that dysbiosis of the gut microbiota exacerbates LPS-induced endometritis by production and migration of succinate from gut to uterine tissues via the gut-uterus axis, then activates the SUCNR1. This identifies gut-derived succinate as a novel target for treating endometritis, and it indicates that targeting the gut microbiota and its metabolism could be a potential strategy for intervention in endometritis.}, }
@article {pmid39735707, year = {2024}, author = {Chu, C and Behera, TR and Huang, Y and Qiu, W and Chen, J and Shen, Q}, title = {Research progress of gut microbiome and diabetic nephropathy.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1490314}, pmid = {39735707}, issn = {2296-858X}, abstract = {Diabetic nephropathy is an important complication of diabetic microvascular injury, and it is also an important cause of end-stage renal disease. Its high prevalence and disability rate significantly impacts patients' quality of life while imposing substantial social and economic burdens. Gut microbiota affects host metabolism, multiple organ functions, and regulates host health throughout the life cycle. With the rapid development of technology, researchers have found that gut microbiota is closely related to the progression of diabetic kidney disease. This review explores the role of gut microbiome in diabetic nephropathy summarizing proposed mechanisms of progression and focusing on microbial metabolites, intestinal barrier disruption, inflammation, filtration barrier damage and renal fibrosis. This review also examines the mechanism and limitations of current treatments, including drugs, fecal microbiota transplantation, and lifestyle changes, offering new perspectives on prevention and treatment.}, }
@article {pmid39735647, year = {2024}, author = {Wang, H and Li, S and Zhang, L and Zhang, N}, title = {The role of fecal microbiota transplantation in type 2 diabetes mellitus treatment.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1469165}, pmid = {39735647}, issn = {1664-2392}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Diabetes Mellitus, Type 2/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {In contemporary microbial research, the exploration of interactions between microorganisms and multicellular hosts constitutes a burgeoning field. The gut microbiota is increasingly acknowledged as a pivotal contributor to various disorders within the endocrine system, encompassing conditions such as diabetes and thyroid diseases. A surge in research activities has been witnessed in recent years, elucidating the intricate interplay between the gut microbiota and disorders of the endocrine system. Simultaneously, fecal microbiota transplantation (FMT) has emerged as a focal point, garnering substantial attention in both biomedical and clinical spheres. Research endeavors have uncovered the remarkable therapeutic efficacy of FMT across diverse diseases, with particular emphasis on its application in addressing type 2 diabetes mellitus (T2DM) and associated com-plications. Consequently, this manuscript accentuates the intimate connection between the gut microbiota and disorders within the endocrine system, with a specific focus on exploring the potential of FMT as an intervention in the therapeutic landscape of T2DM and its complications. Furthermore, the article scrutinizes concerns inherent in treatment modalities centered around the gut microbiota, proposing viable solutions to address these issues.}, }
@article {pmid39735273, year = {2024}, author = {Patnaik, S and Durairajan, SSK and Singh, AK and Krishnamoorthi, S and Iyaswamy, A and Mandavi, SP and Jeewon, R and Williams, LL}, title = {Role of Candida species in pathogenesis, immune regulation, and prognostic tools for managing ulcerative colitis and Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {48}, pages = {5212-5220}, pmid = {39735273}, issn = {2219-2840}, mesh = {Humans ; *Crohn Disease/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; *Colitis, Ulcerative/microbiology/immunology/diagnosis/therapy ; *Dysbiosis/immunology/microbiology ; Prognosis ; Candida albicans/immunology/pathogenicity/isolation &amp; purification ; Immunity, Mucosal ; Candida/immunology/pathogenicity/isolation &amp; purification ; Candidiasis/immunology/microbiology/diagnosis ; Host-Pathogen Interactions ; Intestinal Mucosa/microbiology/immunology ; }, abstract = {The gut microbiome plays a key role in the pathogenesis and disease activity of inflammatory bowel disease (IBD). While research has focused on the bacterial microbiome, recent studies have shifted towards host genetics and host-fungal interactions. The mycobiota is a vital component of the gastrointestinal microbial community and plays a significant role in immune regulation. Among fungi, Candida species, particularly Candida albicans (C. albicans), have been extensively studied due to their dual role as gut commensals and invasive pathogens. Recent findings indicate that various strains of C. albicans exhibit considerable differences in virulence factors, impacting IBD's pathophysiology. Intestinal fungal dysbiosis and antifungal mucosal immunity may be associated to IBD, especially Crohn's disease (CD). This article discusses intestinal fungal dysbiosis and antifungal immunity in healthy individuals and CD patients. It discusses factors influencing the mycobiome's role in IBD pathogenesis and highlights significant contributions from the scientific community aimed at enhancing understanding of the mycobiome and encouraging further research and targeted intervention studies on specific fungal populations. Our article also provided insights into a recent study by Wu et al in the World Journal of Gastroenterology regarding the role of the gut microbiota in the pathogenesis of CD.}, }
@article {pmid39735176, year = {2025}, author = {Bhatia, Z and Kumar, S and Seshadri, S}, title = {Fecal microbiota transplantation as a potential therapeutic approach to improve impaired glucose tolerance via gut microbiota modulation in rat model.}, journal = {Journal of diabetes and metabolic disorders}, volume = {24}, number = {1}, pages = {28}, pmid = {39735176}, issn = {2251-6581}, abstract = {OBJECTIVES: To investigate the impact of diet-induced gut microbiota alterations on type 2 diabetes and assess the therapeutic potential of Fecal Microbiota Transplantation (FMT) in restoring a balanced gut microenvironment.<br><br>METHODS: To induce type 2 diabetes, rats were fed a high-sugar high-fat diet (HSFD) for 90 days. After diabetes induction, animals were divided into an HSFD control group, a metformin group (100&#xa0;mg/kg), and an FMT group (100&#xa0;mg/kg), receiving treatment for an additional 90 days. Fasting blood glucose levels, glucose tolerance, serum markers (HbA1C, free fatty acids, lipopolysaccharides, pro-inflammatory and anti-inflammatory cytokines), and gut microbiota profiles via cecal metagenome sequencing were analyzed post-treatment.<br><br>RESULTS: FMT effectively restored gut microbiota composition to a profile similar to healthy controls, rebalancing the Firmicutes/Bacteroidetes ratio and increasing beneficial taxa, including Prevotella ruminicola, Akkermansia muciniphila, Roseburia, and Faecalibacterium prausnitzii. These microbial shifts corresponded with significant metabolic improvements: FMT reduced inflammatory markers (LPS and FFA), lowered HbA1c, and improved glucose tolerance. Enhanced gut barrier integrity observed in FMT-treated animals likely contributed to reduced endotoxemia and systemic inflammation, distinguishing FMT's metabolic effects from those of metformin. Notably, FMT addressed the dysbiosis associated with HSFD, promoting microbial resilience and mitigating the metabolic disruptions linked to type 2 diabetes.<br><br>CONCLUSION: These findings underscore the potential of FMT as a targeted therapeutic approach to modulate gut microbiota composition and mitigate metabolic dysregulation induced by high sugar high fat diet.}, }
@article {pmid39733842, year = {2025}, author = {Mamun, AA and Geng, P and Wang, S and Shao, C and Xiao, J}, title = {IUPHAR review: Targeted therapies of signaling pathways based on the gut microbiome in autism spectrum disorders: Mechanistic and therapeutic applications.}, journal = {Pharmacological research}, volume = {211}, number = {}, pages = {107559}, doi = {10.1016/j.phrs.2024.107559}, pmid = {39733842}, issn = {1096-1186}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Autism Spectrum Disorder/therapy/microbiology/metabolism ; *Probiotics/therapeutic use ; Animals ; *Signal Transduction ; *Fecal Microbiota Transplantation ; *Brain-Gut Axis/physiology ; *Prebiotics/administration &amp; dosage ; Dysbiosis/therapy ; }, abstract = {Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by impairments in social interaction, communication and repetitive activities. Gut microbiota significantly influences behavior and neurodevelopment by regulating the gut-brain axis. This review explores gut microbiota-influenced treatments for ASD, focusing on their therapeutic applications and mechanistic insights. In addition, this review discusses the interactions between gut microbiota and the immune, metabolic and neuroendocrine systems, focusing on crucial microbial metabolites including short-chain fatty acids (SCFAs) and several neurotransmitters. Furthermore, the review explores various therapy methods including fecal microbiota transplantation, dietary modifications, probiotics and prebiotics and evaluates their safety and efficacy in reducing ASD symptoms. The discussion shows the potential of customized microbiome-based therapeutics and the integration of multi-omics methods to understand the underlying mechanisms. Moreover, the review explores the intricate relationship between gut microbiota and ASD, aiming to develop innovative therapies that utilize the gut microbiome to improve the clinical outcomes of ASD patients. Microbial metabolites such as neurotransmitter precursors, tryptophan metabolites and SCFAs affect brain development and behavior. Symptoms of ASD are linked to changes in these metabolites. Dysbiosis in the gut microbiome may impact neuroinflammatory processes linked to autism, negatively affecting immune signaling pathways. Research indicates that probiotics and prebiotics can improve gut microbiota and alleviate symptoms in ASD patients. Fecal microbiota transplantation may also improve behavioral symptoms and restore gut microbiota balance. The review emphasizes the need for further research on gut microbiota modification as a potential therapeutic approach for ASD, highlighting its potential in clinical settings.}, }
@article {pmid39733798, year = {2025}, author = {Luo, Y and Li, M and Luo, D and Tang, B}, title = {Gut Microbiota: An Important Participant in Childhood Obesity.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {16}, number = {2}, pages = {100362}, pmid = {39733798}, issn = {2156-5376}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Pediatric Obesity/microbiology ; Child ; Probiotics/therapeutic use ; Prebiotics ; Diet ; Inflammation/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {Increasing prevalence of childhood obesity has emerged as a critical global public health concern. Recent studies have challenged the previous belief that obesity was solely a result of excessive caloric intake. Alterations in early-life gut microbiota can contribute to childhood obesity through their influence on nutrient absorption and metabolism, initiation of inflammatory responses, and regulation of gut-brain communication. The gut microbiota is increasingly acknowledged to play a crucial role in human health, as certain beneficial bacteria have been scientifically proven to possess the capacity to reduce body fat content and enhance intestinal barrier function and their metabolic products to exhibit anti-inflammatory effect. Examples of such microbes include bifidobacteria, Akkermansia muciniphila, and Lactobacillus reuteri. In contrast, an increase in Enterobacteriaceae and propionate-producing bacteria (Prevotellaceae and Veillonellaceae) has been implicated in the induction of low-grade systemic inflammation and disturbances in lipid metabolism, which can predispose individuals to obesity. Studies have demonstrated that modulating the gut microbiota through diet, lifestyle changes, prebiotics, probiotics, or fecal microbiota transplantation may contribute to gut homeostasis and the management of obesity and its associated comorbidities. This review aimed to elucidate the impact of alterations in gut microbiota composition during early life on childhood obesity and explores the mechanisms by which gut microbiota contributes to the pathogenesis of obesity and specifically focused on recent advances in using short-chain fatty acids for regulating gut microbiota and ameliorating obesity. Additionally, it aimed to discuss the therapeutic strategies for childhood obesity from the perspective of gut microbiota, aiming to provide a theoretical foundation for interventions targeting pediatric obesity based on gut microbiota.}, }
@article {pmid39732757, year = {2024}, author = {Jasiński, M and Biliński, J and Maciejewska, M and Ostrowska, K and Rusicka-Krzewska, P and Konarski, W and Podsiadły, E and Snarski, E and Basak, GW}, title = {Impact of gut colonization by antibiotic-resistant bacteria on the outcomes of autologous stem cell transplantation in multiple myeloma.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {31221}, pmid = {39732757}, issn = {2045-2322}, mesh = {Humans ; *Multiple Myeloma/therapy/microbiology ; Male ; Middle Aged ; Female ; *Transplantation, Autologous ; Aged ; Retrospective Studies ; *Gastrointestinal Microbiome ; Adult ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Drug Resistance, Bacterial ; Treatment Outcome ; }, abstract = {Patients undergoing autologous stem cell transplantation (auto-SCT) face elevated risks of infections. Additionally, patients colonized in the gastrointestinal tract with antibiotic-resistant bacteria (ARB) are at higher risk of infection with ARB and other infections. Therefore, patients colonized with ARB before auto-SCT should present with an exceptionally high incidence of infections. According to current literature, ARB colonization is the surrogate marker for dysbiosis, which is known to be associated with a diagnosis of multiple myeloma (MM). Given that, this retrospective study aimed to assess the influence of ARB colonization on infection rates, hematopoiesis regeneration, mucositis, overall survival, and progression-free survival following auto-SCT in MM. Data from 138 MM patients undergoing 141 auto-SCT were analyzed, with 15% showing ARB colonization. Among colonized patients, ESBL-producing gram-negative rods predominated. Patients with gut ARB colonization had significantly higher infection rates than non-colonized individuals (52 vs. 26%, P = 0.02), particularly bloodstream infections (43% vs. 14%, P = 0.004). Colonized patients also tended to exhibit shorter survival rates although there was no statistical significance (1-year and 2-year OS; non-colonized vs. colonized; 97 and 92% vs. 90 and 86%; p = 0.054). Based on our results, gut colonization before auto-SCT negatively affects treatment outcomes.}, }
@article {pmid39732731, year = {2024}, author = {Lu, Y and Huangfu, S and Ma, C and Ding, Y and Zhang, Y and Zhou, C and Liao, L and Li, M and You, J and Chen, Y and Wang, D and Chen, A and Jiang, B}, title = {Exosomes derived from umbilical cord mesenchymal stem cells promote healing of complex perianal fistulas in rats.}, journal = {Stem cell research &amp; therapy}, volume = {15}, number = {1}, pages = {414}, pmid = {39732731}, issn = {1757-6512}, support = {BE2022674//General Program of Jiangsu Province Social Development-oriented Special Fund Project/ ; No. 82004365//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Exosomes/metabolism ; Rats ; *Mesenchymal Stem Cells/metabolism/cytology ; *Wound Healing ; *Rats, Sprague-Dawley ; *Umbilical Cord/cytology ; *Rectal Fistula/therapy/metabolism ; Humans ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; Disease Models, Animal ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Mesenchymal Stem Cell Transplantation/methods ; }, abstract = {BACKGROUND: Complex perianal fistulas, challenging to treat and prone to recurrence, often require surgical intervention that may cause fecal incontinence and lower quality of life due to large surgical wounds and potential sphincter damage. Human umbilical cord-derived MSCs (hUC-MSCs) and their exosomes (hUCMSCs-Exo) may promote wound healing.<br><br>METHODS: This study assessed the efficacy, mechanisms, and safety of these exosomes in treating complex perianal fistulas in SD rats. We established a rat model, divided rats with fistulas into the control and the exosome groups. We assessed treatment efficacy through ultrasound, clinical observations, and histopathological analysis. We also evaluated the activation of the HIF-1&#x3b1;/TGF-&#x3b2;/Smad signaling pathway via PCR and Western blot and assessed serological markers for HIF-1&#x3b1; and inflammatory indices through ELISA. We analyzed gut microbiota and the systemic metabolic environment via untargeted metabolomics.<br><br>RESULTS: The hUCMSCs-Exo effectively promoted healing of wound, regulated the immune balance enhanced collagen synthesis and angiogenesis in the perianal fistulas model of rats, and regulated the gut microbiota and metabolomic profiles. Results of PCR and Western blot analyses indicated that the exosomes activated HIF-1&#x3b1;/TGF-&#x3b2;/Smad signaling pathways. To the dosages tested, the 10ug/100ul concentration (medium dose) was found to be the most effective to the treatment of complex perianal fistulas.<br><br>CONCLUSIONS: The hUCMSCs-Exo significantly promoted the healing of wound in perianal fistulas of rats and demonstrated higher safety. The underlying mechanism facilitating the healing process was likely associated with the activation of the HIF-1&#x3b1;/TGF-&#x3b2;/Smad signaling pathway.}, }
@article {pmid39732352, year = {2025}, author = {Kamath, S and Sokolenko, E and Collins, K and Chan, NSL and Mills, N and Clark, SR and Marques, FZ and Joyce, P}, title = {IUPHAR themed review: The gut microbiome in schizophrenia.}, journal = {Pharmacological research}, volume = {211}, number = {}, pages = {107561}, doi = {10.1016/j.phrs.2024.107561}, pmid = {39732352}, issn = {1096-1186}, mesh = {Animals ; Humans ; *Antipsychotic Agents/therapeutic use/adverse effects ; *Brain-Gut Axis/drug effects/physiology ; *Dysbiosis/diagnosis/microbiology/physiopathology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/physiology ; Prebiotics/administration &amp; dosage ; *Probiotics/administration &amp; dosage ; *Schizophrenia/drug therapy/metabolism/microbiology/physiopathology ; }, abstract = {Gut microbial dysbiosis or altered gut microbial consortium, in schizophrenia suggests a pathogenic role through the gut-brain axis, influencing neuroinflammatory and neurotransmitter pathways critical to psychotic, affective, and cognitive symptoms. Paradoxically, conventional psychotropic interventions may exacerbate this dysbiosis, with antipsychotics, particularly olanzapine, demonstrating profound effects on microbial architecture through disruption of bacterial phyla ratios, diminished taxonomic diversity, and attenuated short-chain fatty acid synthesis. To address these challenges, novel therapeutic strategies targeting the gut microbiome, encompassing probiotic supplementation, prebiotic compounds, faecal microbiota transplantation, and rationalised co-pharmacotherapy, show promise in attenuating antipsychotic-induced metabolic disruptions while enhancing therapeutic efficacy. Harnessing such insights, precision medicine approaches promise to transform antipsychotic prescribing practices by identifying patients at risk of metabolic side effects based on their microbial profiles. This IUPHAR review collates the current literature landscape of the gut-brain axis and its intricate relationship with schizophrenia while advocating for integrating microbiome assessments and therapeutic management. Such a fundamental shift in proposing microbiome-informed psychotropic prescriptions to optimise therapeutic efficacy and reduce adverse metabolic impacts would align antipsychotic treatments with microbiome safety, prioritising 'gut-neutral' or gut-favourable drugs to safeguard long-term patient outcomes in schizophrenia therapy.}, }
@article {pmid39731142, year = {2024}, author = {Yang, Y and Wang, L and Zhuang, T and Xu, T and Ji, M and Wang, Q}, title = {Washed microbiota transplantation stopped recurrent sepsis in a patient with myelofibrosis: a case report.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {78}, pmid = {39731142}, issn = {1757-4749}, abstract = {BACKGROUND: Sepsis represents the most prevalent infectious complication and the primary cause of mortality in myeloproliferative neoplasms (MPN). The risk of sepsis and the difficulty of treatment are significantly increased in MPN patients due to the need for immunomodulators and antibiotics.<br><br>CASE PRESENTATION: On June 9, 2023, a 69-year-old male was admitted to the hospital. Following a battery of tests, the diagnosis of sepsis due to Escherichia coli was ultimately established. The patient was administered amoxicillin clavulanate potassium intravenously. In light of the patient's recurrent sepsis and the likelihood that the source of infection is the intestinal tract, we advised that the patient undergo washed microbiota transplantation (WMT) via a colonic transendoscopic enteral tube (TET).<br><br>CONCLUSIONS: WMT as the new method of fecal microbiota transplantation (FMT) successfully cured the recurrent sepsis in this case, indicating the novel option for challenging the refractory or serious infections.}, }
@article {pmid39729440, year = {2024}, author = {Cibulkova, I and Rehorova, V and Soukupova, H and Waldauf, P and Cahova, M and Manak, J and Matejovic, M and Duska, F}, title = {Allogenic faecal microbiota transplantation for antibiotic-associated diarrhoea in critically ill patients (FEBATRICE)-Study protocol for a multi-centre randomised controlled trial (phase II).}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0310180}, pmid = {39729440}, issn = {1932-6203}, mesh = {Female ; Humans ; Male ; *Anti-Bacterial Agents/adverse effects/therapeutic use ; *Critical Illness ; *Diarrhea/therapy/microbiology ; Dysbiosis/therapy/microbiology ; *Fecal Microbiota Transplantation/methods/adverse effects ; Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; Prospective Studies ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; }, abstract = {BACKGROUND: Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea.<br><br>METHODS: Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea. We will exclude patients with ongoing sepsis, need of systemic antibiotics, or those after recent bowel surgery or any other reason that prevents the FMT. Randomisation will be in 1:1 ratio. Patients in the control group will receive standard treatment based on oral diosmectite. In the intervention group, patients will receive, in addition to the standard of care, faecal microbiota transplantation via rectal tube, in the form of a preparation mixed from 7 thawed aliquots (50 mL) made from fresh stool of 7 healthy unrelated donors and quarantined deep frozen for 3 to 12 months. Primary outcome is treatment failure defined as intervention not delivered or diarrhoea persisting at day 7 after randomisation. Secondary outcomes include safety measures such as systemic inflammatory response, adverse events, and also diarrhoea recurrence within 28 days. Exploratory outcomes focus on gut barrier function and composition of intestinal microbiota.<br><br>DISCUSSION: Faecal microbiota transplantation has been effective for dysbiosis in non-critically ill patients with recurrent C. difficile infections and it is plausible to hypothesize that it will be equally effective for symptoms of dysbiosis in the critically ill patients. In addition, animal experiments and observational data suggest other benefits such as reduced colonization with multi-drug resistant bacteria and improved gut barrier and immune function. The frozen faeces from unrelated donors are immediately available when needed, unlike those from the relatives, who require lengthy investigation. Using multiple donors maximises graft microbiota diversity. Nonetheless, in vulnerable critically ill patients, Faecal microbiota transplantation might lead to bacterial translocation and unforeseen complications. From growing number of case series it is clear that its off label use in the critically ill patients is increasing and that there is a burning need to objectively assess its efficacy and safety, which this trial aims.<br><br>TRIAL REGISTRATION: www.clinicaltrials.gov (NCT05430269).}, }
@article {pmid39728458, year = {2024}, author = {Voziki, A and Deda, O and Kachrimanidou, M}, title = {The Efficacy of Fecal Microbiota Transplantation in Mouse Models Infected with Clostridioides difficile from the Perspective of Metabolic Profiling: A Systematic Review.}, journal = {Metabolites}, volume = {14}, number = {12}, pages = {}, pmid = {39728458}, issn = {2218-1989}, abstract = {Objectives: This systematic review evaluates the effectiveness of fecal microbiota transplantation (FMT) in treating Clostridioides difficile infection (CDI) in mouse models using a metabolomics-based approach. Methods: A comprehensive search was conducted in three databases (PubMed, Scopus, Google Scholar) from 10 April 2024 to 17 June 2024. Out of the 460 research studies reviewed and subjected to exclusion criteria, only 5 studies met all the inclusion criteria and were analyzed. Results: These studies consistently showed that FMT effectively restored gut microbiota and altered metabolic profiles, particularly increasing short-chain fatty acids (SCFAs) and secondary bile acids, which inhibited C. difficile growth. FMT proved superior to antibiotic and probiotic treatments in re-establishing a healthy gut microbiome, as evidenced by significant changes in the amino acid and carbohydrate levels. Despite its promise, variability in the outcomes-due to factors such as immune status, treatment protocols, and donor microbiome differences-underscores the need for standardization. Rather than pursuing immediate standardization, the documentation of factors such as donor and recipient microbiome profiles, preparation methods, and administration details could help identify optimal configurations for specific contexts and patient needs. In all the studies, FMT was successful in restoring the metabolic profile in mice. Conclusions: These findings align with the clinical data from CDI patients, suggesting that FMT holds potential as a therapeutic strategy for gut health restoration and CDI management. Further studies could pave the way for adoption in clinical practice.}, }
@article {pmid39726974, year = {2024}, author = {Ebrahimi, R and Farsi, Y and Nejadghaderi, SA}, title = {Fecal microbiota transplantation for glaucoma; a potential emerging treatment strategy.}, journal = {Current research in microbial sciences}, volume = {7}, number = {}, pages = {100314}, pmid = {39726974}, issn = {2666-5174}, abstract = {Glaucoma is the primary cause of irreversible blindness globally. Different glaucoma subtypes are identified by their underlying mechanisms, and treatment options differ by its pathogenesis. Current management includes topical medications to lower intraocular pressure and surgical procedures like trabeculoplasty and glaucoma drainage implants. Fecal microbiota transplantation (FMT) is an almost effective and safe treatment option for recurrent Clostridium difficile infection. The relationship between bacterial populations, metabolites, and inflammatory pathways in retinal diseases indicates possible therapeutic strategies. Thus, incorporating host microbiota-based therapies could offer an additional treatment option for glaucoma patients. Here, we propose that combining FMT with standard glaucoma treatments may benefit those affected by this condition. Also, the potential safety, efficacy, cost-effectiveness and clinical applications are discussed.}, }
@article {pmid39726854, year = {2025}, author = {Minerbi, A and Khoutorsky, A and Shir, Y}, title = {Decoding the connection: unraveling the role of gut microbiome in fibromyalgia.}, journal = {Pain reports}, volume = {10}, number = {1}, pages = {e1224}, pmid = {39726854}, issn = {2471-2531}, abstract = {The gut microbiome is emerging as a critical player in the pathophysiology of fibromyalgia, offering mechanistic insights as well as potential diagnostic and therapeutic applications.}, }
@article {pmid39725607, year = {2025}, author = {Wang, P and Wang, R and Zhao, W and Zhao, Y and Wang, D and Zhao, S and Ge, Z and Ma, Y and Zhao, X}, title = {Gut microbiota-derived 4-hydroxyphenylacetic acid from resveratrol supplementation prevents obesity through SIRT1 signaling activation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446391}, doi = {10.1080/19490976.2024.2446391}, pmid = {39725607}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Sirtuin 1/metabolism ; *Obesity/metabolism/prevention &amp; control/microbiology ; *Resveratrol/pharmacology/administration &amp; dosage ; Mice ; *Phenylacetates/pharmacology/metabolism ; *Signal Transduction/drug effects ; *Diet, High-Fat/adverse effects ; Male ; *Mice, Inbred C57BL ; Dysbiosis/microbiology/prevention &amp; control ; Adipose Tissue, White/metabolism/drug effects ; Anti-Obesity Agents/pharmacology/administration &amp; dosage ; Dietary Supplements ; Bacteria/classification/metabolism/drug effects/genetics ; Fecal Microbiota Transplantation ; }, abstract = {Resveratrol (RSV), a natural polyphenol, has been suggested to influence glucose and lipid metabolism. However, the underlying molecular mechanism of its action remains largely unknown due to its multiple biological targets and low bioavailability. In this study, we demonstrate that RSV supplementation ameliorates high-fat-diet (HFD)-induced gut microbiota dysbiosis, enhancing the abundance of anti-obesity bacterial strains such as Akkermansia, Bacteroides and Blautia. The critical role of gut microbiota in RSV-mediated anti-obesity effects was confirmed through antibiotic-induced microbiome depletion and fecal microbiota transplantation (FMT), which showed that RSV treatment effectively mitigates body weight, histopathological damage, glucose dysregulation and systematic inflammation associated with HFD. Metabolomics analysis revealed that RSV supplementation significantly increases the levels of the gut microbial flavonoid catabolite 4-hydroxyphenylacetic acid (4-HPA). Notably, 4-HPA was sufficient to reverse obesity and glucose intolerance in HFD-fed mice. Mechanistically,4-HPA treatment markedly regulates SIRT1 signaling pathways and induces the expression of beige fat and thermogenesis-specific markers in white adipose tissue (WAT). These beneficial effects of 4-HPA are partially abolished by EX527, a known SIRT1 inhibitor. Collectively, our findings indicate that RSV improve obesity through a gut microbiota-derived 4-HPA-SIRT1 axis, highlighting gut microbiota metabolites as a promising target for obesity prevention.}, }
@article {pmid39725475, year = {2025}, author = {Yang, RF and Wu, W and Zhang, P}, title = {Research Progress on Obesity-Associated Kidney Diseases.}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {47}, number = {1}, pages = {77-85}, doi = {10.3881/j.issn.1000-503X.16098}, pmid = {39725475}, issn = {1000-503X}, mesh = {Humans ; *Obesity/complications ; *Kidney Diseases/etiology/therapy ; Renin-Angiotensin System ; Insulin Resistance ; }, abstract = {The pathogenesis of obesity-associated kidney disease (OAKD) involves many aspects,including the overactivation of the renin-angiotensin-aldosterone system,insulin resistance,chronic inflammation,disorder of lipid metabolism and imbalance of gut microecology.Treatment strategies for OAKD focus on lifestyle adjustments,pharmacotherapy,bariatric surgery,and fecal microbiota transplantation.A deeper understanding of the hazards of OAKD and its pathogenesis will contribute to the development of personalized and precise strategies for prevention,diagnosis and treatment of OAKD in the future.}, }
@article {pmid39724461, year = {2024}, author = {Mahmoudian, F and Gheshlagh, SR and Hemati, M and Farhadi, S and Eslami, M}, title = {The influence of microbiota on the efficacy and toxicity of immunotherapy in cancer treatment.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {86}, pmid = {39724461}, issn = {1573-4978}, mesh = {Animals ; Humans ; *Dysbiosis/immunology/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods/adverse effects ; *Neoplasms/immunology/microbiology/therapy ; }, abstract = {Immunotherapy, which uses the body's immune system to fight cancer cells, has gained attention recently as a breakthrough in cancer treatment. Although significant progress has been made, obstacles still exist since cancers are skilled at avoiding immune monitoring. The gut microbiota is being looked at more and more in modern research as a critical component in improving the results of immunotherapy. Through modulating both innate and adaptive immune responses, the gut microbiome has a significant impact on cancer immunotherapy. The effectiveness of treatment and the way the immune system responds are significantly influenced by some microorganisms and the metabolites they produce, especially short-chain fatty acids. On the other hand, dysbiosis and persistent inflammation in the gut environment might unintentionally accelerate the growth of tumors, which makes the complex relationship between the makeup of the microbiota and cancer treatment more challenging. Gut microbiota plays a crucial role in immunotherapy effectiveness. Improved microbial diversity leads to better treatment responses, with some taxa like Bacteroides and Ruminococcaceae being linked to better responses to immune checkpoint inhibitors. Dysbiotic conditions can worsen immune-related side effects and reduce treatment effectiveness. Strategies manipulating gut microbiota, such as fecal microbiota transplantation, antibiotic therapies, and dietary interventions, could optimize immunotherapy response and prognosis. However, standardizing these interventions for different cancer types and patient populations is challenging due to individual microbiome differences. Future research should combine microbiome research with AI and rigorous clinical trials for individualized cancer treatments.}, }
@article {pmid39717506, year = {2025}, author = {Bloom, PP and Chung, RT}, title = {The future of clinical trials of gut microbiome therapeutics in cirrhosis.}, journal = {JHEP reports : innovation in hepatology}, volume = {7}, number = {1}, pages = {101234}, pmid = {39717506}, issn = {2589-5559}, abstract = {The last two decades have witnessed an explosion of microbiome research, including in hepatology, with studies demonstrating altered microbial composition in liver disease. More recently, efforts have been made to understand the association of microbiome features with clinical outcomes and to develop therapeutics targeting the microbiome. While microbiome therapeutics hold much promise, their unique features pose certain challenges for the design and conduct of clinical trials. Herein, we will briefly review indications for microbiome therapeutics in cirrhosis, currently available microbiome therapeutics, and the biological pathways targeted by these therapies. We will then focus on the best practices and important considerations for clinical trials of gut microbiome therapeutics in cirrhosis.}, }
@article {pmid39716346, year = {2025}, author = {Li, Y and Wang, K and Shen, D and Liu, J and Li, S and Liu, L and Nagaoka, K and Li, C}, title = {Mogroside V protects lipopolysaccharides-induced lung inflammation chicken via suppressing inflammation mediated by the Th17 through the gut-lung axis.}, journal = {Journal of animal science}, volume = {103}, number = {}, pages = {}, pmid = {39716346}, issn = {1525-3163}, support = {32372935//National Nature Science Foundation of China/ ; }, mesh = {Animals ; *Chickens ; Lipopolysaccharides/toxicity ; Lung/drug effects ; *Poultry Diseases/chemically induced/prevention &amp; control/drug therapy ; *Th17 Cells/drug effects ; *Pneumonia/veterinary/chemically induced/prevention &amp; control/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation/veterinary ; Male ; }, abstract = {Lipopolysaccharide (LPS) exposure triggers pulmonary inflammation, leading to compromised lung function in broiler. As amplified by policy restrictions on antibiotic usage, seeking antibiotic alternatives has become imperative. Mogroside V (MGV) has been reported to have a beneficial role in livestock and poultry production due to its remarkable antiinflammatory effects. Despite evidence showcasing MGV's efficacy against LPS-triggered lung inflammation, its precise mechanism of action remains elusive. In this study, we transplanted normal fecal microbiota (CF), fecal microbiota modified by MGV (MF), and sterile fecal filtrate (MS) into broiler with LPS-induced pneumonia. The results showed that through fecal microbiota transplantation (FMT), transplanting MGV-induced microbial populations significantly mitigated tissue damage induced by LPS and enhanced the mRNA level of pulmonary tight junction proteins and mucoprotein (P < 0.01). The expression levels of RORα (P < 0.001), Foxp3 (P < 0.01), and PD-L1 (P < 0.01) were significantly increased in the MF group than CF group. The concentrations of IL-6 and IL-17 in broilers lung tissue of MF group were lower than those in broilers of CF group (P < 0.05). Furthermore, the concentration of TGF-β in broilers serum of MS and MF groups was higher than those in broilers of CF group (P < 0.05). Microbial community analysis demonstrated that at genus level, the harmful bacterial populations Escherichia-Shigella and Helicobacter following FMT treatment were significantly reduced in MF group (P < 0.05), potentially mediating its protective effects. Compared with CF group, valerate content and FFAR2 mRNA expression levels in MF group were significantly increased (P < 0.05). The study suggests that MGV via the gut-lung axis, attenuates Th17-mediated inflammation, offering promise as a therapeutic strategy against LPS-induced lung inflammation in chickens.}, }
@article {pmid39715825, year = {2024}, author = {Bornbusch, SL and Crosier, A and Gentry, L and Delaski, KM and Maslanka, M and Muletz-Wolz, CR}, title = {Fecal microbiota transplants facilitate post-antibiotic recovery of gut microbiota in cheetahs (Acinonyx jubatus).}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {1689}, pmid = {39715825}, issn = {2399-3642}, support = {NSF IOS-2131060//National Science Foundation (NSF)/ ; }, mesh = {*Acinonyx ; *Gastrointestinal Microbiome ; Animals ; *Anti-Bacterial Agents/pharmacology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Male ; Female ; }, abstract = {Burgeoning study of host-associated microbiomes has accelerated the development of microbial therapies, including fecal microbiota transplants (FMTs). FMTs provide host-specific microbial supplementation, with applicability across host species. Studying FMTs can simultaneously provide comparative frameworks for understanding microbial therapies in diverse microbial systems and improve the health of managed wildlife. Ex-situ carnivores, including cheetahs (Acinonyx jubatus), often suffer from intractable gut infections similar to those treated with antibiotics and FMTs in humans, providing a valuable system for testing FMT efficacy. Using an experimental approach in 21 cheetahs, we tested whether autologous FMTs facilitated post-antibiotic recovery of gut microbiota. We used 16S rRNA sequencing and microbial source tracking to characterize antibiotic-induced microbial extirpations and signatures of FMT engraftment for single versus multiple FMTs. We found that antibiotics extirpated abundant bacteria and FMTs quickened post-antibiotic recovery via engraftment of bacteria that may facilitate protein digestion and butyrate production (Fusobacterium). Although multiple FMTs better sustained microbial recovery compared to a single FMT, one FMT improved recovery compared to antibiotics alone. This study elucidated the dynamics of microbiome modulation in a non-model system and improves foundations for reproducible, low-cost, low-dose, and minimally invasive FMT protocols, emphasizing the scientific and applied value of FMTs across species.}, }
@article {pmid39715151, year = {2025}, author = {Nie, P and Hu, L and You, T and Jia, T and Xu, H}, title = {Lead Mediated Lipopolysaccharides Exacerbates Fatty Liver Processes in High-Fat Diets-Induced Mice.}, journal = {Environmental toxicology}, volume = {40}, number = {5}, pages = {750-763}, doi = {10.1002/tox.24463}, pmid = {39715151}, issn = {1522-7278}, support = {82060606//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; *Lipopolysaccharides/toxicity ; Gastrointestinal Microbiome/drug effects ; Male ; Liver/drug effects/pathology/metabolism ; *Lead/toxicity ; *Fatty Liver/chemically induced/pathology ; Mice ; Obesity ; *Non-alcoholic Fatty Liver Disease ; }, abstract = {Obesity leads to a variety of health risks, and lead, which is ranked second in Agency for Toxic Substances and Disease Registry's priority list of harmful substances, may be more harmful to individuals that are obese. C57BL/6 mice were fed a normal diet or a high-fat diet with or without exposure to 1 g/L lead exposure in drinking water for 8 consecutive weeks. Serum and hepatic biochemistry analysis, histopathological observation, and RT-qPCR were used to explore the potential mechanism of liver damage in obese individuals after Pb exposure, and fecal microbiota transplantation was performed to investigate the role of the gut microbiota in the progression of fatty liver disease. We found that the progression of fatty liver disease induced by high-fat diets was accelerated by chronic lead intake. In addition, the occurrences of liver injury in recipient mice suggested the role of the gut microbiota. These findings indicated that the combination of lead and a HFD exacerbated hepatic lipotoxicity by activating LPS-mediated inflammation, and that gut microbiota disorders and impaired intestinal barrier function play pivotal roles in the progression of fatty liver disease.}, }
@article {pmid39714951, year = {2025}, author = {Li, W and Wang, Y and Shi, Y and He, F and Zhao, Z and Liu, J and Gao, Z and Zhang, J and Shen, X}, title = {The gut microbiota mediates memory impairment under high-altitude hypoxia via the gut-brain axis in mice.}, journal = {The FEBS journal}, volume = {292}, number = {4}, pages = {809-826}, doi = {10.1111/febs.17365}, pmid = {39714951}, issn = {1742-4658}, support = {81973073//National Natural Science Foundation of China/ ; 82173481//National Natural Science Foundation of China/ ; 82204089//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Memory Disorders/microbiology/physiopathology/etiology ; *Hypoxia/microbiology/complications/physiopathology ; Fecal Microbiota Transplantation ; Male ; Blood-Brain Barrier/metabolism/microbiology ; Altitude ; Hippocampus ; *Altitude Sickness/microbiology/complications ; Mice, Inbred C57BL ; Brain ; *Brain-Gut Axis ; Disease Models, Animal ; }, abstract = {Hypoxia is a predominant risk factor at high altitudes, and evidence suggests that high-altitude hypoxia alters the gut microbiota, which plays an essential regulatory role in memory function. However, the causal relationship between the gut microbiota and memory impairment under hypoxic conditions remains unclear. In this study, we employed a high-altitude hypoxia model combined with fecal microbiota transplantation (FMT) approach in mice to explore the effects of the gut microbiota on memory impairment in a hypoxic environment. We observed that high-altitude hypoxia exposure reduced short- and long-term memory and hippocampus-dependent fear memory abilities, along with decreased relative abundance of Ligilactobacillus and Muribaculum. Moreover, hypoxic conditions increased intestinal and blood-brain barrier permeability. FMT from hypoxia-exposed mice into naïve antibiotic-treated mice resulted in similar memory impairments, Ligilactobacillus and Muribaculum abundance changes, and increased intestinal/blood-brain barrier permeability. Correlation analysis showed a robust positive association between Ligilactobacillus and Muribaculum with hippocampus-dependent contextual fear memory. Likewise, Ligilactobacillus was positively correlated with short-term memory. Therefore, Ligilactobacillus and Muribaculum may be key microbes in reducing memory ability in hypoxia, with the intestinal and blood-brain barriers as primary pathways. Our findings provide further evidence for the potential regulatory mechanism by which gut microbiota dysbiosis may contribute to memory impairment in a high-altitude environment.}, }
@article {pmid39712898, year = {2024}, author = {Tang, M and Wu, Y and Liang, J and Yang, S and Huang, Z and Hu, J and Yang, Q and Liu, F and Li, S}, title = {Gut microbiota has important roles in the obstructive sleep apnea-induced inflammation and consequent neurocognitive impairment.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1457348}, pmid = {39712898}, issn = {1664-302X}, abstract = {Obstructive sleep apnea (OSA) is a state of sleep disorder, characterized by repetitive episodes of apnea and chronic intermittent hypoxia. OSA has an extremely high prevalence worldwide and represents a serious challenge to public health, yet its severity is frequently underestimated. It is now well established that neurocognitive dysfunction, manifested as deficits in attention, memory, and executive functions, is a common complication observed in patients with OSA, whereas the specific pathogenesis remains poorly understood, despite the likelihood of involvement of inflammation. Here, we provide an overview of the current state of the art, demonstrating the intimacy of OSA with inflammation and cognitive impairment. Subsequently, we present the recent findings on the investigation of gut microbiota alteration in the OSA conditions, based on both patients-based clinical studies and animal models of OSA. We present an insightful discussion on the role of changes in the abundance of specific gut microbial members, including short-chain fatty acid (SCFA)-producers and/or microbes with pathogenic potential, in the pathogenesis of inflammation and further cognitive dysfunction. The transplantation of fecal microbiota from the mouse model of OSA can elicit inflammation and neurobehavioral disorders in naïve mice, thereby validating the causal relationship to inflammation and cognitive abnormality. This work calls for greater attention on OSA and the associated inflammation, which require timely and effective therapy to protect the brain from irreversible damage. This work also suggests that modification of the gut microbiota using prebiotics, probiotics or fecal microbiota transplantation may represent a potential adjuvant therapy for OSA.}, }
@article {pmid39712559, year = {2024}, author = {Özdemir, &#xd6;}, title = {Relation between dysbiosis and inborn errors of immunity.}, journal = {World journal of methodology}, volume = {14}, number = {4}, pages = {96380}, pmid = {39712559}, issn = {2222-0682}, abstract = {Inborn errors of immunity (IEI) disorders, formerly primary immune deficiency diseases, are a heterogeneous group of disorders with variable hereditary transitions, clinical manifestations, complications and varying disease severity. Many of the clinical symptoms, signs and complications in IEI patients can be attributed to inflammatory and immune dysregulatory processes due to loss of microbial diversity (dysbiosis). For example, in common variable immunodeficiency patients, the diversity of bacteria, but not fungi, in the gut microbiota has been found to be reduced and significantly altered. Again, this was associated with a more severe disease phenotype. Compromise of the STAT3/Th17 pathway in hyper-IgE syndrome may lead to dysbiosis of the oral microbiota in these patients, causing Candida albicans to switch from commensal to pathogenic. Modification of the microbiota can be used as a therapeutic approach in patients with IEI. Prebiotics, probiotics, postbiotics and fecal microbiota transplantation can be used to restore the balance of the gut microbiota and reduce pathogenicity in IEI patients. Clinical trials are currently underway to understand the impact of this dysbiosis on the phenotype of IEI diseases and its role in their treatment.}, }
@article {pmid39712189, year = {2024}, author = {Lusk, S and Memos, NK and Rauschmayer, A and Ray, RS}, title = {The microbiome is dispensable for normal respiratory function and chemoreflexes in mice.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1481394}, pmid = {39712189}, issn = {1664-042X}, abstract = {Increasing evidence indicates an association between microbiome composition and respiratory homeostasis and disease, particularly disordered breathing, such as obstructive sleep apnea. Previous work showing respiratory disruption is limited by the methodology employed to disrupt, eliminate, or remove the microbiome by antibiotic depletion. Our work utilized germ-free mice born without a microbiome and described respiratory alterations. We used whole-body flow through barometric plethysmography to assay conscious and unrestrained C57BL/6J germ-free (GF, n = 24) and specific-pathogen-free (SPF, n = 28) adult mice (with an intact microbiome) in normoxic (21% O2,79% N2) conditions and during challenges in hypercapnic (5% CO2, 21% O2, 74% N2) and hypoxic (10% O2, 90% N2) environments. Following initial plethysmography analysis, we performed fecal transplants to test the ability of gut microbiome establishment to rescue any observed phenotypes. Data were comprehensively analyzed using our newly published respiratory analysis software, Breathe Easy, to identify alterations in respiratory parameters, including ventilatory frequency, tidal volume, ventilation, apnea frequency, and sigh frequency. We also considered possible metabolic changes by analyzing oxygen consumption, carbon dioxide production, and ventilatory equivalents of oxygen. We also assayed GF and SPF neonates in an autoresuscitation assay to understand the effects of the microbiome on cardiorespiratory stressors in early development. We found several differences in baseline and recovery cardiorespiratory parameters in the neonates and differences in body weight at both ages studied. However, there was no difference in the overall survival of the neonates, and in contrast to prior studies utilizing gut microbial depletion, we found no consequential respiratory alterations in GF versus SPF adult mice at baseline or following fecal transplant in any groups. Interestingly, we did see alterations in oxygen consumption in the GF adult mice, which suggests an altered metabolic demand. Results from this study suggest that microbiome alteration in mice may not play as large a role in respiratory outcomes when a less severe methodology to eliminate the microbiome is utilized.}, }
@article {pmid39711145, year = {2025}, author = {Qian, M and Jiang, Z and Xu, C and Wang, L and Hu, N}, title = {Changes in the gut microbiota and derived fecal metabolites may play a role in tacrolimus-induced diabetes in mice.}, journal = {Future microbiology}, volume = {20}, number = {3}, pages = {237-246}, pmid = {39711145}, issn = {1746-0921}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/genetics ; *Tacrolimus/adverse effects/administration &amp; dosage ; *Feces/chemistry/microbiology ; Mice ; Male ; *Diabetes Mellitus, Experimental/microbiology/chemically induced/metabolism ; RNA, Ribosomal, 16S/genetics ; Metabolomics ; Lipid Metabolism/drug effects ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Immunosuppressive Agents/adverse effects/administration &amp; dosage ; Mice, Inbred C57BL ; Disease Models, Animal ; Metabolome ; }, abstract = {AIMS: A notable scarcity of research has focused on examining alterations in gut microbiota and its metabolites within tacrolimus (TAC)-induced diabetes models.<br><br>METHODS: Tacrolimus-induced changes in glucose and lipid metabolism indices were analyzed through different routes of administration. The potential role of gut microbiota and its metabolites in TAC-induced diabetes was investigated using 16S rRNA sequencing and non-targeted metabolomics.<br><br>RESULTS: After intraperitoneal(ip) and oral(po) administration of TAC, the &#x3b1;-diversity index of gut microbiota was significantly increased. The gut microbiota of the three groups of mice was significantly separated, and there were significant changes in composition and functional genes. Fecal metabolites changed significantly after TAC administration by different routes, and 53 metabolites (38 down-regulated and 15 up-regulated) were identified (CON vs. TACip). Similarly, 29 metabolites (8 down-regulated and 21 up-regulated) were identified (CON vs. TACpo). KEGG pathway analysis identified 4 and 13 significantly altered metabolic pathways, respectively. Correlation analysis suggested that microbiota and metabolites were involved in the pathogenesis of TAC-induced diabetes.<br><br>CONCLUSION: This study investigated the alterations in gut microbiota and fecal metabolites in TAC-induced diabetic mice and evaluated the correlation between these changes. These findings provide valuable insights into potential biomarkers in the development of TAC-induced diabetes.}, }
@article {pmid39710789, year = {2024}, author = {Wang, Y and Bai, M and Peng, Q and Li, L and Tian, F and Guo, Y and Jing, C}, title = {Angiogenesis, a key point in the association of gut microbiota and its metabolites with disease.}, journal = {European journal of medical research}, volume = {29}, number = {1}, pages = {614}, pmid = {39710789}, issn = {2047-783X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neovascularization, Pathologic/metabolism/microbiology ; Neoplasms/microbiology/metabolism/immunology ; Inflammation/metabolism ; Cardiovascular Diseases/microbiology/metabolism/etiology ; Animals ; Neurodegenerative Diseases/microbiology/metabolism ; Angiogenesis ; }, abstract = {The gut microbiota is a complex and dynamic ecosystem that plays a crucial role in human health and disease, including obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, inflammatory bowel disease, and cancer. Chronic inflammation is a common feature of these diseases and is closely related to angiogenesis (the process of forming new blood vessels), which is often dysregulated in pathological conditions. Inflammation potentially acts as a central mediator. This abstract aims to elucidate the connection between the gut microbiota and angiogenesis in various diseases. The gut microbiota influences angiogenesis through various mechanisms, including the production of metabolites that directly or indirectly affect vascularization. For example, short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate are known to regulate immune responses and inflammation, thereby affecting angiogenesis. In the context of cardiovascular diseases, the gut microbiota promotes atherosclerosis and vascular dysfunction by producing trimethylamine N-oxide (TMAO) and other metabolites that promote inflammation and endothelial dysfunction. Similarly, in neurodegenerative diseases, the gut microbiota may influence neuroinflammation and the integrity of the blood-brain barrier, thereby affecting angiogenesis. In cases of fractures and wound healing, the gut microbiota promotes angiogenesis by activating inflammatory responses and immune effects, facilitating the healing of tissue damage. In cancer, the gut microbiota can either inhibit or promote tumor growth and angiogenesis, depending on the specific bacterial composition and their metabolites. For instance, some bacteria can activate inflammasomes, leading to the production of inflammatory factors that alter the tumor immune microenvironment and activate angiogenesis-related signaling pathways, affecting tumor angiogenesis and metastasis. Some bacteria can directly interact with tumor cells, activating angiogenesis-related signaling pathways. Diet, as a modifiable factor, significantly influences angiogenesis through diet-derived microbial metabolites. Diet can rapidly alter the composition of the microbiota and its metabolic activity, thereby changing the concentration of microbial-derived metabolites and profoundly affecting the host's immune response and angiogenesis. For example, a high animal protein diet promotes the production of pro-atherogenic metabolites like TMAO, activating inflammatory pathways and interfering with platelet function, which is associated with the severity of coronary artery plaques, peripheral artery disease, and cardiovascular diseases. A diet rich in dietary fiber promotes the production of SCFAs, which act as ligands for cell surface or intracellular receptors, regulating various biological processes, including inflammation, tissue homeostasis, and immune responses, thereby influencing angiogenesis. In summary, the role of the gut microbiota in angiogenesis is multifaceted, playing an important role in disease progression by affecting various biological processes such as inflammation, immune responses, and multiple signaling pathways. Diet-derived microbial metabolites play a crucial role in linking the gut microbiota and angiogenesis. Understanding the complex interactions between diet, the gut microbiota, and angiogenesis has the potential to uncover novel therapeutic targets for managing these conditions. Therefore, interventions targeting the gut microbiota and its metabolites, such as through fecal microbiota transplantation (FMT) and the application of probiotics to alter the composition of the gut microbiota and enhance the production of beneficial metabolites, present a promising therapeutic strategy.}, }
@article {pmid39710683, year = {2024}, author = {Yarahmadi, A and Afkhami, H and Javadi, A and Kashfi, M}, title = {Understanding the complex function of gut microbiota: its impact on the pathogenesis of obesity and beyond: a comprehensive review.}, journal = {Diabetology &amp; metabolic syndrome}, volume = {16}, number = {1}, pages = {308}, pmid = {39710683}, issn = {1758-5996}, abstract = {Obesity is a multifactorial condition influenced by genetic, environmental, and microbiome-related factors. The gut microbiome plays a vital role in maintaining intestinal health, increasing mucus creation, helping the intestinal epithelium mend, and regulating short-chain fatty acid (SCFA) production. These tasks are vital for managing metabolism and maintaining energy balance. Dysbiosis-an imbalance in the microbiome-leads to increased appetite and the rise of metabolic disorders, both fuel obesity and its issues. Furthermore, childhood obesity connects with unique shifts in gut microbiota makeup. For instance, there is a surge in pro-inflammatory bacteria compared to children who are not obese. Considering the intricate nature and variety of the gut microbiota, additional investigations are necessary to clarify its exact involvement in the beginnings and advancement of obesity and related metabolic dilemmas. Currently, therapeutic methods like probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), dietary interventions like Mediterranean and ketogenic diets, and physical activity show potential in adjusting the gut microbiome to fight obesity and aid weight loss. Furthermore, the review underscores the integration of microbial metabolites with pharmacological agents such as orlistat and semaglutide in restoring microbial homeostasis. However, more clinical tests are essential to refine the doses, frequency, and lasting effectiveness of these treatments. This narrative overview compiles the existing knowledge on the multifaceted role of gut microbiota in obesity and much more, showcasing possible treatment strategies for addressing these health challenges.}, }
@article {pmid39706182, year = {2025}, author = {Jiang, Y and Huang, Z and Sun, W and Huang, J and Xu, Y and Liao, Y and Jin, T and Li, Q and Ho, IHT and Zou, Y and Zhu, W and Li, Q and Qin, F and Zhang, X and Shi, S and Zhang, N and Yang, S and Xie, W and Wu, S and Tan, L and Zhang, L and Chen, H and Gin, T and Chan, MTV and Wu, WKK and Xiao, L and Liu, X}, title = {Roseburia intestinalis-derived butyrate alleviates neuropathic pain.}, journal = {Cell host &amp; microbe}, volume = {33}, number = {1}, pages = {104-118.e7}, doi = {10.1016/j.chom.2024.11.013}, pmid = {39706182}, issn = {1934-6069}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Neuralgia/microbiology/metabolism ; *Butyrates/metabolism ; Humans ; *Receptors, G-Protein-Coupled/metabolism ; *Fecal Microbiota Transplantation ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; Solitary Nucleus/metabolism ; Clostridiales ; Vagus Nerve ; Probiotics ; Central Amygdaloid Nucleus/metabolism ; Mice, Knockout ; Female ; Neurons/metabolism ; }, abstract = {Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles. Functionally, fecal microbiota transplantation from patients with PHN to mice heightened pain sensitivity. Administration of Roseburia intestinalis, a bacterium both depleted in patients with shingles and PHN, alleviated peripheral nerve injury-induced pain in mice. R. intestinalis enhanced vagal neurotransmission to the nucleus tractus solitarius (NTS) to suppress the central amygdala (CeA), a brain region involved in pain perception. R. intestinalis-generated butyrate activated vagal neurons through the receptor, G protein-coupled receptor 41 (GPR41). Vagal knockout of Gpr41 abolished the effects of R. intestinalis on the NTS-CeA circuit and reduced pain behaviors. Overall, we established a microbiota-based model for PHN risk assessment and identified R. intestinalis as a potential pain-alleviating probiotic.}, }
@article {pmid39703540, year = {2024}, author = {Finnegan, YE and Neill, HR and Prpa, EJ and Pot, B}, title = {"Gut" to grips with the science of the microbiome - a symposium report.}, journal = {Gut microbiome (Cambridge, England)}, volume = {5}, number = {}, pages = {e11}, pmid = {39703540}, issn = {2632-2897}, abstract = {The latest Yakult Science Study Day was held virtually on 2 November 2023. Aimed at healthcare professionals, researchers, and students, a variety of experts explored the latest gut microbiome research and what it means in practice. The morning sessions discussed the role of the microbiome in health and disease, the rapid advancements in DNA sequencing and implications for personalised nutrition, the current state of evidence on health benefits associated with fermented foods, prebiotics and probiotics and the challenges involved in interpreting research in this area. The afternoon session considered the emerging research on the microbiota-gut-brain axis in mediating effects of food on mood, the bidirectional impact of menopause on the gut microbiota, and the interplay between the gut and skin with implications for the treatment of rare and common skin disorders. The session ended with an update on the use of faecal microbiota transplant in both research and clinical practice. Undoubtedly, the gut microbiome is emerging as a key conductor of human health, both in relation to gastrointestinal and non-gastrointestinal outcomes. As research continues to elucidate mechanisms of action and confirm their effects in human trials, the gut microbiome should be a key consideration within a holistic approach to health moving forward.}, }
@article {pmid39703374, year = {2024}, author = {Chen, T and Wang, N and Hao, Y and Fu, L}, title = {Fecal microbiota transplantation from postmenopausal osteoporosis human donors accelerated bone mass loss in mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1488017}, pmid = {39703374}, issn = {2235-2988}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Humans ; Mice ; *Gastrointestinal Microbiome ; Female ; *Feces/microbiology ; *Osteoporosis, Postmenopausal/microbiology ; Disease Models, Animal ; Bacteria/classification/isolation &amp; purification/genetics ; Bone Density ; Middle Aged ; Zonula Occludens-1 Protein/metabolism ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVES: To investigate the effect of gut microbiota from postmenopausal osteoporosis patients on bone mass in mice.<br><br>METHODS: Fecal samples were collected from postmenopausal women with normal bone mass (Con, n=5) and postmenopausal women with osteoporosis (Op, n=5). Microbial composition was identified by shallow shotgun sequencing. Then fecal samples were transplanted into pseudo-sterile mice previously treated with antibiotics for 4 weeks. These mice were categorized into two groups: the Vehicle group (n=7) received fecal samples from individuals with normal bone mass, and the FMT group (n=7) received fecal samples from individuals with osteoporosis. After 8 weeks, bone mass, intestinal microbial composition, intestinal permeability and inflammation were assessed, followed by a correlation analysis.<br><br>RESULTS: The bone mass was significantly reduced in the FMT group. Microbiota sequencing showed that Shannon index (p < 0.05) and Simpson index (p < 0.05) were significantly increased in Op groups, and &#x3b2; diversity showed significant differences. the recipient mice were similar. linear discriminant analysis effect size (LEfSe) analysis of mice showed that Halobiforma, Enterorhabdus, Alistipes, and Butyricimonas were significantly enriched in the FMT group. Lachnospiraceae and Oscillibacter were significantly enriched in the Vehicle group. H&amp;E staining of intestinal tissues showed obvious intestinal mucosal injury in mice. Intestinal immunohistochemistry showed that the expression of Claudin and ZO-1 in the intestinal tissue of the FMT group mice was decreased. The FITC-Dextran (FD-4) absorption rate and serum soluble CD14 (sCD14) content were increased in FMT mice. Correlation analysis showed that these dominant genera were significantly associated with bone metabolism and intestinal permeability, and were associated with the enrichment of specific enzymes. Serum and bone tissue inflammatory cytokines detection showed that the expression of TNF-&#x3b1; and IL-17A in the FMT group were significantly increased.<br><br>CONCLUSION: Overall, our findings suggested gut microbiota from postmenopausal osteoporosis patients accelerate bone mass loss in mice. Aberrant gut microbiota might play a causal role in the process of bone mass loss mediated by inflammation after the destruction of the intestinal barrier.}, }
@article {pmid39702789, year = {2025}, author = {Kaur, S and Patel, BCK and Collen, A and Malhotra, R}, title = {The microbiome and the eye: a new era in ophthalmology.}, journal = {Eye (London, England)}, volume = {39}, number = {3}, pages = {436-448}, pmid = {39702789}, issn = {1476-5454}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Eye Diseases/microbiology/therapy ; *Ophthalmology/trends ; *Eye/microbiology ; *Microbiota/physiology ; Fecal Microbiota Transplantation ; }, abstract = {The human microbiome has progressively been recognised for its role in various disease processes. In ophthalmology, complex interactions between the gut and distinct ocular microbiota within each structure and microenvironment of the eye has advanced our knowledge on the multi-directional relationships of these ecosystems. Increasingly, studies have shown that modulation of the microbiome can be achieved through faecal microbiota transplantation and synbiotics producing favourable outcomes for ophthalmic diseases. As ophthalmologists, we are obliged to educate our patients on measures to cultivate a healthy gut microbiome through a range of holistic measures. Further integrative studies combining microbial metagenomics, metatranscriptomics and metabolomics are necessary to fully characterise the human microbiome and enable targeted therapeutic interventions.}, }
@article {pmid39701930, year = {2024}, author = {Wen, J and Wang, S and Sun, K and Wang, H and Yuan, Z and Deng, W}, title = {Chang-Wei-Qing Combined with PD-1 Inhibitor Alleviates Colitis-Associated Colorectal Tumorigenesis by Modulating the Gut Microbiota and Restoring Intestinal Barrier.}, journal = {Biological procedures online}, volume = {26}, number = {1}, pages = {32}, pmid = {39701930}, issn = {1480-9222}, support = {ptkwws202002//Shanghai Putuo District Health and Health System Science and Technology Innovation Project/ ; 2021tszk01//Shanghai Putuo District Health and Health System Clinical Specialty Construction Project/ ; ZY[2021-2023]-0302//Shanghai Municipal Health Commission's Shanghai Further Accelerating Traditional Chinese Medicine Development Three-Year Action Plan Project/ ; }, abstract = {Chang-Wei-Qing (CWQ) is a widely recognized Traditional Chinese Medicine (TCM) formulation composed of Astragalus, Codonopsis, Atractylodes, Poria, Coix seed, Akebia trifoliata Koidz, Sargentodoxa cuneata, and Vitis quinquangularis Rehd. This formulation has garnered significant interest for its positive effects in mitigating colorectal cancer, and when combined with PD-1, it affects some gut microbiota associated with tumor infiltrating lymphocytes cells. However, the biological rationale underlying the suppression of colitis-associated colorectal cancer (CAC) in AOM/DSS-treated mice by CWQ combined with PD-1 inhibitor remains to be explored. Our aim is to explore the chemopreventive effect of CWQ combined with PD-1 inhibitor on CAC, with a focus on modulating the gut microbiota. A mouse model of CAC was established using azoxymethane (AOM) and dextran sulfate sodium (DSS) treatment. Pathological evaluation of tissue samples included immunohistochemistry and hematoxylin and eosin staining. Intestinal barrier function was assessed by transmission electron microscopy. Fecal microbiota and metabolites were analyzed through 16 S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Mice treated with antibiotics served as models for fecal microbiota transplantation. CWQ combined with PD-1 inhibitor suppressed CAC in AOM/DSS-treated mice. This combined therapy effectively alleviated gut dysbiosis in the CAC model by increasing microbial diversity, enriching probiotic populations such as Limosilactobacillus and Bifidobacterium, and reducing pathogenic bacteria like Desulfovibrio. Additionally, CWQ combined with PD-1 inhibitor downregulated metabolites associated with the NF-kappa B signaling pathway. The combined treatment also significantly improved intestinal barrier function in CAC mice. Transmission electron microscopy of the CWQ combined with PD-1 inhibitor group showed enhanced cellular integrity, a relatively normal mitochondrial structure with intact membranes, and a more abundant, unexpanded endoplasmic reticulum, underscoring the protective effects of this combination on intestinal barrier integrity. Transcriptomic analysis further demonstrated that the combined therapy upregulated genes involved in tight and adherens junctions, while downregulating genes linked to innate immune responses. CWQ combined with PD-1 inhibitor can ameliorate dysbiosis in the AOM/DSS mouse model, with the metabolites of the gut microbiome potentially possessing anti-inflammatory activity. Moreover, CWQ combined with PD-1 inhibitor improves intestinal barrier function, thereby effectively inhibiting the occurrence and development of CAC.}, }
@article {pmid39699275, year = {2025}, author = {Wang, Y and Xue, Y and Xu, H and Zhu, Q and Qin, K and He, Z and Huang, A and Mu, M and Tao, X}, title = {Pediococcus acidilactici Y01 reduces HFD-induced obesity via altering gut microbiota and metabolomic profiles and modulating adipose tissue macrophage M1/M2 polarization.}, journal = {Food &amp; function}, volume = {16}, number = {2}, pages = {554-569}, doi = {10.1039/d4fo04301d}, pmid = {39699275}, issn = {2042-650X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Obesity/metabolism/microbiology ; Mice ; *Pediococcus acidilactici/physiology ; *Macrophages/metabolism/drug effects ; Male ; *Adipose Tissue/metabolism ; Diet, High-Fat/adverse effects ; *Probiotics/pharmacology ; Mice, Inbred C57BL ; }, abstract = {Obesity-related metabolic syndrome is intimately associated with infiltrated adipose tissue macrophages (ATMs), gut microbiota, and metabolic disorders. Pediococcus acidilactici holds the potential to mitigate obesity; however, there exist strain-specific functionalities and diverse mechanisms, which deserve extensive exploration. This study aims to explore the potential of P. acidilactici Y01, isolated from traditional sour whey, in alleviating HFD-induced metabolic syndrome in mice and elucidating its underlying mechanism. The results showed that P. acidilactici Y01 could inhibit the increase of body weight gain, the deposition of fat, lipid disorders and chronic low-grade inflammation, improve glucose tolerance and insulin resistance, and could reduce adipose tissue inflammation by decreasing M1-type ATMs and increasing M2-type ATMs. Meanwhile, P. acidilactici Y01 significantly increased the abundance of potentially beneficial intestinal bacteria, such as Akkermansia, Alistipes, Bifidobacterium, Lachnospiraceae_NK4A136_group, Lactobacillus, norank_f__Muribaculaceae, and Parabacteroides, and partially restored the levels of metabolites, such as phosphatidylcholines, glycerophosphocholines, sphingolipids and unsaturated fatty acids. The fecal microbiota transplantation experiment demonstrated that P. acidilactici Y01 ameliorated obesity-related metabolic syndrome by modulating the polarization of M1/M2 ATMs mediated by gut microbiota. Overall, as a dietary supplement, P. acidilactici Y01 has good potential in the prevention and treatment of obesity.}, }
@article {pmid39699220, year = {2025}, author = {Li, T and Hu, G and Fu, S and Qin, D and Song, Z}, title = {Phillyrin ameliorates DSS-induced colitis in mice via modulating the gut microbiota and inhibiting the NF-κB/MLCK pathway.}, journal = {Microbiology spectrum}, volume = {13}, number = {2}, pages = {e0200624}, pmid = {39699220}, issn = {2165-0497}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; Dextran Sulfate/adverse effects ; *NF-kappa B/metabolism ; *Myosin-Light-Chain Kinase/metabolism ; *Colitis/chemically induced/drug therapy ; Disease Models, Animal ; Male ; Anti-Inflammatory Agents/pharmacology ; Forsythia/chemistry ; Signal Transduction/drug effects ; *Pyrans/pharmacology/administration &amp; dosage ; Mice, Inbred C57BL ; *Colitis, Ulcerative/drug therapy/chemically induced ; Glucosides ; }, abstract = {Phillyrin (PHY), also known as forsythin, is an active constituent isolated from the fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae). It exhibits anti-inflammatory, anti-viral, and antioxidant properties. However, the precise impact of PHY on colitis induced by dextran sodium sulfate (DSS) and its mechanism remain elusive. The present investigation revealed that PHY (12.5, 25.0, and 50.0 mg/kg) exhibited significant therapeutic efficacy in protecting mice against DSS-induced colitis. This effect was manifested as reduced weight loss, a shortened colon, increased secretion of inflammatory factors, increased intestinal permeability, and an enhanced disease activity index in mice with ulcerative colitis (UC). Molecular investigations have determined that PHY mitigates the nuclear translocation of nuclear factor kappa B, thereby downregulating myosin light-chain kinase-driven myosin light-chain phosphorylation. This mechanism results in the preservation of the integrity of the intestinal barrier. The outcomes of 16S rRNA sequencing suggest that PHY (50 mg/kg) augmented the relative abundance of certain probiotic strains, including Lactobacillaceae and Lachnospiraceae. Additionally, PHY supplementation elevated the short-chain fatty acid contents within the intestinal contents of mice with UC. In conclusion, pre-treatment with PHY may ameliorate the DSS-induced UC in mice by lowering the expression of inflammatory factors, protecting intestinal barrier function, and enhancing the structure of the intestinal flora.IMPORTANCEThe protective effect of phillyrin on DSS-induced colitis was explained for the first time, and the anti-inflammatory effect of phillyrin was demonstrated by fecal microbiota transplantation experiments mainly through intestinal flora.}, }
@article {pmid39694919, year = {2025}, author = {Zhang, Y and Ji, X and Chang, K and Yin, H and Zhao, M and Zhao, L}, title = {The regulatory effect of chitooligosaccharides on islet inflammation in T2D individuals after islet cell transplantation: the mechanism behind Candida albicans abundance and macrophage polarization.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2442051}, pmid = {39694919}, issn = {1949-0984}, mesh = {Animals ; *Candida albicans/drug effects ; *Oligosaccharides/pharmacology ; Mice ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Macrophages/drug effects/immunology ; *Diabetes Mellitus, Type 2/microbiology ; *Islets of Langerhans Transplantation ; *Myeloid Differentiation Factor 88/metabolism/genetics ; *Inflammation ; Male ; Mice, Inbred C57BL ; Chitosan/pharmacology ; Islets of Langerhans/drug effects ; STAT6 Transcription Factor/metabolism/genetics ; NF-kappa B/metabolism/genetics ; }, abstract = {Islet cell transplantation (ICT) represents a promising therapeutic approach for addressing diabetes mellitus. However, the islet inflammation during transplantation significantly reduces the surgical outcome rate, which is related to the polarization of macrophages. Chitooligosaccharides (COS) was previously reported which could modulate the immune system, alleviate inflammation, regulate gut microecology, and repair the intestinal barrier. Therefore, we hypothesized COS could relieve pancreatic inflammation by regulating macrophage polarization and gut microbiota. First, 18S rDNA gene sequencing was performed on fecal samples from the ICT population, showing abnormally increased amount of Candida albicans, possibly causing pancreatic inflammation. Functional oligosaccharides responsible for regulating macrophage polarization and inhibiting the growth of Candida albicans were screened. Afterwards, human flora-associated T2D (HMA-T2D) mouse models of gut microbiota were established, and the ability of the selected oligosaccharides were validated in vivo to alleviate inflammation and regulate gut microbiota. The results indicated that ICT significantly decreased the alpha diversity of gut fungal, altered fungal community structures, and increased Candida albicans abundance. Moreover, Candida albicans promoted M1 macrophage polarization, leading to islet inflammation. COS inhibited Candida albicans growth, suppressed the MyD88-NF-κB pathway, activated STAT6, inhibited M1, and promoted M2 macrophage polarization. Furthermore, COS-treated HMA-T2D mice displayed lower M1 macrophage differentiation and higher M2 macrophage numbers. Additionally, COS also enhanced ZO-1 and Occludin mRNA expression, reduced Candida albicans abundance, and balanced gut microecology. This study illustrated that COS modulated macrophage polarization via the MyD88/NF-κB and STAT6 pathways, repaired the intestinal barrier, and reduced Candida albicans abundance to alleviate islet inflammation.}, }
@article {pmid39691426, year = {2024}, author = {Yu, J and Chen, YX and Wang, JW and Wu, HT}, title = {Research progress on the relationship between traumatic brain injury and brain-gut-microbial axis.}, journal = {Ibrain}, volume = {10}, number = {4}, pages = {477-487}, pmid = {39691426}, issn = {2769-2795}, abstract = {Traumatic brain injury (TBI) is a common disease with a high rate of death and disability, which poses a serious threat to human health; thus, the effective treatment of TBI has been a high priority. The brain-gut-microbial (BGM) axis, as a bidirectional communication network for information exchange between the brain and gut, plays a crucial role in neurological diseases. This article comprehensively explores the interrelationship between the BGM axis and TBI, including its physiological effects, basic pathophysiology, and potential therapeutic strategies. It highlights how the bidirectional regulatory pathways of the BGM axis could provide new insights into clinical TBI treatment and underscores the necessity for advanced research and development of innovative clinical treatments for TBI.}, }
@article {pmid39686442, year = {2024}, author = {Liu, F and Zhang, H and Fan, L and Yu, Q and Wang, S}, title = {Hotspots and development trends of gut microbiota in atopic dermatitis: A bibliometric analysis from 1988 to 2024.}, journal = {Medicine}, volume = {103}, number = {50}, pages = {e40931}, pmid = {39686442}, issn = {1536-5964}, mesh = {*Dermatitis, Atopic/microbiology/therapy ; *Gastrointestinal Microbiome ; Humans ; *Bibliometrics ; Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a prevalent inflammatory skin condition that commonly occurs in children. More and more scientific evidence suggests that gut microbiota plays an important role in the pathogenesis of AD, whereas there is no article providing a comprehensive summary and analysis. We aimed to analyze documents on AD and gut microbiota and identify hotspots and development trends in this field.<br><br>METHODS: Articles and reviews in the field of AD and gut microbiota from January 1, 1988 to October 20, 2024 were obtained from the Web of Science Core Collection database. Biblioshiny was utilized for evaluating and visualizing the core authors, journals, countries, documents, trend topics, and hotspots in this field.<br><br>RESULTS: Among 1672 documents, it indicated that the number of annual publications generally increased. The United States had the highest production, impact, and international collaboration. Journal of Allergy and Clinical Immunology was the journal of the maximum publications. Based on keyword co-occurrence and clustering analysis, "stratum-corneum lipids," "probiotics," "prebiotics," "fecal microbiota transplantation," "phage therapy," "short chain fatty-acids," "biologic therapy," and "skin inflammation" represented current trend topics. The pathological and molecular mechanisms and associated therapeutic methods for AD and gut microbiota were the research hotspots. The incorporation of microbiota-based therapies alongside conventional treatments can contribute to better clinical outcomes.<br><br>CONCLUSION: We highlighted that gut microbiota may exacerbate symptoms of AD through various aspects, including immunity, metabolites, and neuroendocrine pathways. More efforts are required to investigate the safety and efficacy of gut microbial management methods for the prevention and treatment of AD.}, }
@article {pmid39684918, year = {2024}, author = {Li, C and Chen, S and Wang, Y and Su, Q}, title = {Microbiome-Based Therapeutics for Insomnia.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684918}, issn = {1422-0067}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/therapy/microbiology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; *Probiotics/therapeutic use ; *Prebiotics/administration &amp; dosage ; Animals ; Synbiotics ; }, abstract = {Insomnia poses considerable risks to both physical and mental health, leading to cognitive impairment, weakened immune function, metabolic dysfunction, cardiovascular issues, and reduced quality of life. Given the significant global increase in insomnia and the growing scientific evidence connecting gut microbiota to this disorder, targeting gut microbiota as an intervention for insomnia has gained popularity. In this review, we summarize current microbiome-based therapeutics for insomnia, including dietary modifications; probiotic, prebiotic, postbiotic, and synbiotic interventions; and fecal microbiota transplantation. Moreover, we assess the capabilities and weaknesses of these technologies to offer valuable insights for future studies.}, }
@article {pmid39684788, year = {2024}, author = {Moreno, RJ and Ashwood, P}, title = {An Update on Microbial Interventions in Autism Spectrum Disorder with Gastrointestinal Symptoms.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684788}, issn = {1422-0067}, support = {HD090214/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Humans ; Anti-Bacterial Agents/therapeutic use ; *Autism Spectrum Disorder/therapy/microbiology ; *Dysbiosis/therapy/microbiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Diseases/therapy/microbiology ; *Gastrointestinal Microbiome ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {In the United States, autism spectrum disorder (ASD) affects 1 in 33 children and is characterized by atypical social interactions, communication difficulties, and intense, restricted interests. Microbial dysbiosis in the gastrointestinal (GI) tract is frequently observed in individuals with ASD, potentially contributing to behavioral manifestations and correlating with worsening severity. Moreover, dysbiosis may contribute to the increased prevalence of GI comorbidities in the ASD population and exacerbate immune dysregulation, further worsening dysbiosis. Over the past 25 years, research on the impact of microbial manipulation on ASD outcomes has gained substantial interest. Various approaches to microbial manipulation have been preclinically and clinically tested, including antibiotic treatment, dietary modifications, prebiotics, probiotics, and fecal microbiota transplantation. Each method has shown varying degrees of success in reducing the severity of ASD behaviors and/or GI symptoms and varying long-term efficacy. In this review, we discuss these microbiome manipulation methods and their outcomes. We also discuss potential microbiome manipulation early in life, as this is a critical period for neurodevelopment.}, }
@article {pmid39682952, year = {2024}, author = {Ma, H and Mueed, A and Ma, Y and Ibrahim, M and Su, L and Wang, Q}, title = {Fecal Microbiota Transplantation Activity of Floccularia luteovirens Polysaccharides and Their Protective Effect on Cyclophosphamide-Induced Immunosuppression and Intestinal Injury in Mice.}, journal = {Foods (Basel, Switzerland)}, volume = {13}, number = {23}, pages = {}, pmid = {39682952}, issn = {2304-8158}, support = {2021YFD1600401//National Key Research and Development Program of China/ ; }, abstract = {Floccularia luteovirens polysaccharides (FLP1s) have potential biological activities. Our previous study showed that FLP1s positively regulated gut immunity and microbiota. However, it is still unclear whether FLP1s mediate gut microbiota in immunosuppressed mice. This research aims to explore the relationship between FLP1-mediated gut microbes and intestinal immunity in immunosuppressed mice through fecal microbiota transplantation (FMT). The results demonstrated that FLP1s exhibited prebiotic and anti-immunosuppressive effects on CTX-induced immunosuppressed mice. FFLP1 treatment (microbiota transplantation from the fecal sample) remarkably elevated the production of sIgA and secretion of the anti-inflammatory cytokines IL-4, TNF-α, and IFN-γ in the intestine of CTX-treated mice, inducing activation of the MAPK pathway. Moreover, FFLP1s mitigated oxidative stress by activating the Nrf2/Keap1 signaling pathway and strengthened the intestinal barrier function by upregulating the expression level of tight junction proteins (occludin, claudin-1, MUC-2, and ZO-1). Furthermore, FFPL1s restored gut dysbiosis in CTX-treated immunosuppressed mice by increasing the abundance of Alloprevotella, Lachnospiraceae, and Bacteroides. They also modified the composition of fecal metabolites, leading to enhanced regulation of lipolysis in adipocytes, the cGMP-PKG pathway, the Rap1 signaling pathway, and ovarian steroidogenesis, as indicated by KEGG pathway analysis. These findings indicate that FLP1s could modulate the response of the intestinal immune system through regulation of the gut microbiota, thus promoting immune activation in CTX-treated immunosuppressed mice. FLP1s can serve as a natural protective agent against CTX-induced immune injury.}, }
@article {pmid39682542, year = {2024}, author = {Morales, C and Ballestero, L and Del Río, P and Barbero-Herranz, R and Olavarrieta, L and Gómez-Artíguez, L and Galeano, J and Avendaño-Ortiz, J and Basterra, J and Del Campo, R}, title = {Should the Faecal Microbiota Composition Be Determined to Certify a Faecal Donor?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {23}, pages = {}, pmid = {39682542}, issn = {2075-4418}, support = {XX//Mikrobiomik/ ; }, abstract = {BACKGROUND/OBJECTIVES: Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent Clostridioides difficile infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification. However, despite the high amount of data generated from the ongoing research studies relating microbiota and health, there is not yet a consensus defining what is a "healthy" microbiota. To date, knowledge of the composition of the microbiota is not a requirement to be a faecal donor. The aim of this work was to evaluate whether the analysis of the composition of the microbiota by massive sequencing of 16S rDNA could be useful in the selection of the faecal donors.<br><br>METHODS: Samples from 10 certified donors from Mikrobiomik Healthcare Company were collected and sequenced using 16S rDNA in a MiSeq (Illumina) platform. Alpha (Chao1 and Shannon indices) and beta diversity (Bray-Curtis) were performed using the bioinformatic web server Microbiome Analyst. The differences in microbial composition at the genera and phyla levels among the donors were evaluated.<br><br>RESULTS: The microbial diversity metric by alpha diversity indexes showed that most donors exhibited a similar microbial diversity and richness, whereas beta diversity by 16S rDNA sequencing revealed significant inter-donor differences, with a more stable microbial composition over time in some donors. The phyla Bacillota and Bacteroidota were predominant in all donors, while the density of other phyla, such as Actinomycota and Pseudomonota, varied among individuals. Each donor exhibited a characteristic genera distribution pattern; however, it was possible to define a microbiome core consisting of the genera Agathobacter, Eubacterium, Bacteroides, Clostridia UCG-014 and Akkermansia. Conclusions: The results suggest that donor certification does not need to rely exclusively on their microbiota composition, as it is unique to each donor. While one donor showed greater microbial diversity and richness, clear criteria for microbial normality and health have yet to be established. Therefore, donor certification should focus more on clinical and lifestyle aspects.}, }
@article {pmid39681213, year = {2025}, author = {Liu, X and Tan, X and Yu, Y and Niu, J and Zhao, B and Wang, Q}, title = {Short chain fatty acids mediates complement C1q pathway alleviation of perioperative neurocognitive disorders.}, journal = {Neuropharmacology}, volume = {265}, number = {}, pages = {110266}, doi = {10.1016/j.neuropharm.2024.110266}, pmid = {39681213}, issn = {1873-7064}, mesh = {Animals ; *Complement C1q/metabolism ; Male ; *Fatty Acids, Volatile/metabolism ; *Rats, Sprague-Dawley ; Rats ; *Gastrointestinal Microbiome/drug effects/physiology ; *Microglia/drug effects/metabolism ; Neurocognitive Disorders/metabolism ; Fecal Microbiota Transplantation ; Postoperative Cognitive Complications/metabolism ; Cognitive Dysfunction/metabolism ; Hippocampus/metabolism/drug effects ; }, abstract = {Perioperative neurocognitive disorders (PND) is one of the most common postoperative complications, which can lead to a harmful impact on self-dependence, longer hospital stays, increased medical costs, morbidity, and mortality amongst older adults. Microglia can modulate synapse elimination involved in the complement component protein 1q (C1q) pathway to induce cognitive dysfunction, which is significantly improved by short chain fatty acids (SCFAs) treatment. Here we investigate the effects of SCFAs treatment on PND via mediating C1q complement pathway. High-throughput sequencing of 16S rDNA from fecal samples of male SD rats was applied to assess the changes in gut microbiota. Fecal microbiota transplantation (FMT) was performed to investigate whether gut microbiota from PND rats could alter cognitive impairment. The blood from the rat tail vein was collected to measure the SCFAs concentrations. Hippocampal and brain tissue samples were obtained to perform Western blots, Golgi and immunofluorescence staining. Primary microglia treated with SCFAs or Histone deacetylase inhibitor were cultured to measure microglial activation states and the expression of acetylated histone. The 16S rDNA sequencing results showed that PND rats had the significant changes in the species diversity of the gut microbiota and the metabolite of specifc species. Gut microbiota from PND rats could alter spatial learning and memory, and meanwhile, the changed SCFAs concentrations in plasma were involved. The synapse elimination in PND rats was strikingly reversed by SCFAs treatment involved in modulation complement C1q via suppressing neuroinflammation. This suggests that a link between gut microbiota dysbiosis and cognitive function impairment is involved in synapse elimination via mediating complement C1q pathway. SCFAs treatment can alleviate PND, the mechanisms of which may be associated with regulating complement C1q pathway.}, }
@article {pmid39680691, year = {2025}, author = {Yang, JC and Lagishetty, V and Aja, E and Arias-Jayo, N and Chang, C and Hauer, M and Katzka, W and Zhou, Y and Sedighian, F and Koletic, C and Liang, F and Dong, TS and Situ, J and Troutman, R and Buri, H and Bhute, S and Simpson, CA and Braun, J and Jacob, N and Jacobs, JP}, title = {Biogeographical distribution of gut microbiome composition and function is partially recapitulated by fecal transplantation into germ-free mice.}, journal = {The ISME journal}, volume = {19}, number = {1}, pages = {}, pmid = {39680691}, issn = {1751-7370}, support = {CDA2 IK2CX001717//Crohn's and Colitis Foundation Career Development/ ; //Vatche and Tamar Manoukian Division of Digestive Diseases/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Fecal Microbiota Transplantation ; Germ-Free Life ; RNA, Ribosomal, 16S/genetics ; *Feces/microbiology ; *Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Mice, Inbred C57BL ; Colon/microbiology ; Specific Pathogen-Free Organisms ; Male ; }, abstract = {Fecal microbiota transplantation has been vital for establishing whether host phenotypes can be conferred through the microbiome. However, whether the existing microbial ecology along the mouse gastrointestinal tract can be recapitulated in germ-free mice colonized with stool remains unknown. We first identified microbes and their predicted functions specific to each of six intestinal regions in three cohorts of specific pathogen-free mice spanning two facilities. Of these region-specific microbes, the health-linked genus Akkermansia was consistently enriched in the lumen of the small intestine compared to the colon. Predictive functional modeling on 16S rRNA gene amplicon sequencing data recapitulated in shotgun sequencing data revealed increased microbial central metabolism, lipolytic fermentation, and cross-feeding in the small intestine, whereas butyrate synthesis was colon-enriched. Neuroactive compound metabolism also demonstrated regional specificity, including small intestine-enriched gamma-aminobutyric acid degradation and colon-enriched tryptophan degradation. Specifically, the jejunum and ileum stood out as sites with high predicted metabolic and neuromodulation activity. Differences between luminal and mucosal microbiomes within each site of the gastrointestinal tract were largely facility-specific, though there were a few consistent patterns in microbial metabolism in specific pathogen-free mice. These included luminal enrichment of central metabolism and cross-feeding within both the small intestine and the colon, and mucosal enrichment of butyrate synthesis within the colon. Across three cohorts of germ-free mice colonized with mice or human stool, compositional and functional region specificity were inconsistently reproduced. These results underscore the importance of investigating the spatial variation of the gut microbiome to better understand its impact on host physiology.}, }
@article {pmid39680624, year = {2025}, author = {Zuo, H and Jiang, W and Gao, J and Ma, Z and Li, C and Peng, Y and Jin, J and Zhan, X and Lv, W and Liu, X and Hu, J and Zhang, M and Jia, Y and Xu, Z and Tang, J and Zheng, R and Zuo, B}, title = {SYISL Knockout Promotes Embryonic Muscle Development of Offspring by Modulating Maternal Gut Microbiota and Fetal Myogenic Cell Dynamics.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {6}, pages = {e2410953}, pmid = {39680624}, issn = {2198-3844}, support = {32221005//National Natural Science Foundation of China/ ; 31900448//National Natural Science Foundation of China/ ; 2021YFA0805903//National Key Research and Development Program of China/ ; 2021CFA018//Natural Science Foundation of Hubei Province/ ; 2021-620-000-001-030//Agricultural Innovation Fund of Hubei Province/ ; 2022ESOF007//Open Fund of Hubei Key Laboratory of Embryonic Stem Cell Research/ ; 2023ZD04072//Biological Breeding-National Science and Technology Major Project/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology/genetics ; Mice ; Mice, Knockout ; *Muscle Development/genetics/physiology ; Female ; Pregnancy ; Histones/metabolism ; Embryonic Development/genetics ; }, abstract = {Embryonic muscle fiber formation determines post-birth muscle fiber totals. The previous research shows SYISL knockout significantly increases muscle fiber numbers and mass in mice, but the mechanism remains unclear. This study confirms that the SYISL gene, maternal gut microbiota, and their interaction significantly affect the number of muscle fibers in mouse embryos through distinct mechanisms, as SYISL knockout alters maternal gut microbiota composition and boosts butyrate levels in embryonic serum. Both fecal microbiota transplantation and butyrate feeding significantly increase muscle fiber numbers in offspring, with butyrate inhibiting histone deacetylases and increasing histone acetylation in embryonic muscle. Combined analysis of RNA-seq between wild-type and SYISL knockout mice with ChIP-seq for H3K9ac and H3K27ac reveals that SYISL and maternal microbiota interaction regulates myogenesis via the butyrate-HDAC-H3K9ac/H3K27ac pathway. Furthermore, scRNA-seq analysis shows that SYISL knockout alone significantly increases the number and proportion of myogenic cells and their dynamics, independently of regulating histone acetylation levels. Cell communication analysis suggests that this may be due to the downregulation of signaling pathways such as MSTN and TGFβ. Overall, multiple pathways are highlighted through which SYISL influences embryonic muscle development, offering valuable insights for treating muscle diseases and improving livestock production.}, }
@article {pmid39679941, year = {2025}, author = {Wu, Q and Wang, J and Tu, C and Chen, P and Deng, Y and Yu, L and Xu, X and Fang, X and Li, W}, title = {Gut microbiota of patients insusceptible to olanzapine-induced fatty liver disease relieves hepatic steatosis in rats.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {328}, number = {2}, pages = {G110-G124}, doi = {10.1152/ajpgi.00167.2024}, pmid = {39679941}, issn = {1522-1547}, support = {82173903//MOST | National Natural Science Foundation of China (NSFC)/ ; 81903686//Natural Science Foundation for Young Scientists of Shanxi Province (Young Scientists Fund of the National Natural Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology/drug effects ; *Olanzapine/adverse effects ; Male ; *Fatty Liver/chemically induced/microbiology/metabolism ; Humans ; Rats ; *Antipsychotic Agents/adverse effects ; Fecal Microbiota Transplantation ; Liver/metabolism/pathology/drug effects ; Middle Aged ; Fatty Acids, Volatile/metabolism ; Female ; *Non-alcoholic Fatty Liver Disease/chemically induced/microbiology ; Rats, Sprague-Dawley ; Leptin/metabolism ; Adult ; Disease Models, Animal ; }, abstract = {Olanzapine-induced fatty liver disease continues to pose vital therapeutic challenges in the treatment of psychiatric disorders. In addition, we observed that some patients were less prone to hepatic steatosis induced by olanzapine. Therefore, we aimed to investigate the role and the underlying mechanism of the intestinal flora in olanzapine-mediated hepatic side effects and explore the possible countermeasures. Our results showed that patients with different susceptibilities to olanzapine-induced fatty liver disease had different gut microbial diversity and composition. Furthermore, we performed fecal microbiota treatment (FMT), and confirmed that the gut microbiome of patients less prone to the fatty liver caused by olanzapine exhibited an alleviation against fatty liver disease in rats. In terms of mechanism, we revealed that the cross talk of leptin with the gut-short-chain fatty acid (SCFA)-liver axis play a critical role in olanzapine-related fatty degeneration in liver. These findings propose a promising strategy for overcoming the issues associated with olanzapine application and will hopefully inspire future in-depth research of fecal microbiota-based therapy in olanzapine-induced fatty liver disease.NEW &amp; NOTEWORTHY Patients who were less inclined to have olanzapine-induced fatty liver had different gut microbiota profiles than did those in the susceptible cohort. Lachnospiraceae, Ruminococcaceae, Oscillospiraceae, Butyricicoccaceae, and Christensenellaceae were enriched in patients who were less prone to fatty liver disease caused by olanzapine. Fecal microbiota treatment (FMT) with these fecal samples promoted short-chain fatty acid (SCFA) production, which attenuated the circulating leptin and inhibited FASN and ACC1, thereby suppressing lipid synthesis in the liver, ultimately leading to alleviation of hepatic steatosis.}, }
@article {pmid39679465, year = {2024}, author = {Wang, M and Ma, Y and Zeng, B and Yang, W and Huang, C and Tang, B}, title = {Influence of the Gut Microbiota, Metabolism and Environment on Neuropsychiatric Disorders.}, journal = {Current reviews in clinical and experimental pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724328335219241202142003}, pmid = {39679465}, issn = {2772-4336}, abstract = {The two-way communication between intestinal microbiota and the central nervous system (the microbiota-gut-brain axis) is involved in the regulation of brain function, neurodevelopment, and aging. The microbiota-gut-brain axis dysfunction may be a predisposition factor for Parkinson's disease (PD), Alzheimer's disease (AD), Autism spectrum disorder (ASD), and other neurological diseases. However, it is not clear whether gut microbiota dysfunction contributes to neuropsychiatric disorders. Changes in the gut microbiota may modulate or modify the effects of environmental factors on neuropsychiatric disorders. Factors that impact neuropsychiatric disorders also influence the gut microbiota, including diet patterns, exercise, stress and functional gastrointestinal disorders. These factors change microbiome composition and function, along with the metabolism and immune responses that cause neuropsychiatric disorders. In this review, we summarized epidemiological and laboratory evidence for the influence of the gut microbiota, metabolism and environmental factors on neuropsychiatric disorders incidence and outcomes. Furthermore, the role of gut microbiota in the two-way interaction between the gut and the brain was also reviewed, including the vagus nerve, microbial metabolism, and immuno-inflammatory responses. We also considered the therapeutic strategies that target gut microbiota in the treatment of neuropsychiatric disorders, including prebiotics, probiotics, Fecal microbiota transplant (FMT), and antibiotics. Based on these data, possible strategies for microbiota-targeted intervention could improve people's lives and prevent neuropsychiatric disorders in the future.}, }
@article {pmid39679306, year = {2024}, author = {Hasnaoui, A and Trigui, R and Giuffrida, M}, title = {Gut microbiota and mesenteric adipose tissue interactions in shaping phenotypes and treatment strategies for Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {46}, pages = {4969-4976}, pmid = {39679306}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/immunology/therapy ; Humans ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology ; *Fecal Microbiota Transplantation ; *Phenotype ; *Mesentery ; Adipose Tissue/immunology/microbiology/metabolism ; Bacterial Translocation ; Cytokines/metabolism ; }, abstract = {In this letter, we commented on the article by Wu et al. We examined the interactions between mesenteric adipose tissue, creeping fat, and gut microbiota in Crohn's disease (CD), a condition marked by chronic gastrointestinal inflammation with a rising global incidence. The pathogenesis of CD involves complex genetic, environmental, and microbial factors. Dysbiosis, which is an imbalance in gut microbial communities, is frequently observed in CD patients, highlighting the pivotal role of the gut microbiota in disease progression and the inflammatory response. Recent studies have shown that mesenteric adipose tissue and creeping fat actively contribute to inflammation by producing proinflammatory cytokines. The relationship between creeping fat and altered microbiota can shift from a potentially protective role to one that encourages bacterial translocation, further complicating disease management. Recent research has suggested that fecal microbiota transplantation could help restore microbial balance, offering a promising therapeutic strategy to improve clinical disease response.}, }
@article {pmid39679283, year = {2024}, author = {Chen, J and Yang, H and Qin, Y and Zhou, X and Ma, Q}, title = {Tryptophan Ameliorates Metabolic Syndrome by Inhibiting Intestinal Farnesoid X Receptor Signaling: The Role of Gut Microbiota-Bile Acid Crosstalk.}, journal = {Research (Washington, D.C.)}, volume = {7}, number = {}, pages = {0515}, pmid = {39679283}, issn = {2639-5274}, abstract = {Background and Aims: Metabolic syndrome (MS) is a progressive metabolic disease characterized by obesity and multiple metabolic disorders. Tryptophan (Trp) is an essential amino acid, and its metabolism is linked to numerous physiological functions and diseases. However, the mechanisms by which Trp affects MS are not fully understood. Methods and Results: In this study, experiments involving a high-fat diet (HFD) and fecal microbiota transplantation (FMT) were conducted to investigate the role of Trp in regulating metabolic disorders. In a mouse model, Trp supplementation inhibited intestinal farnesoid X receptor (FXR) signaling and promoted hepatic bile acid (BA) synthesis and excretion, accompanied by elevated levels of conjugated BAs and the ratio of non-12-OH to 12-OH BAs in hepatic and fecal BA profiles. As Trp alters the gut microbiota and the abundance of bile salt hydrolase (BSH)-enriched microbes, we collected fresh feces from Trp-supplemented mice and performed FMT and sterile fecal filtrate (SFF) inoculations in HFD-treated mice. FMT and SFF not only displayed lipid-lowering properties but also inhibited intestinal FXR signaling and increased hepatic BA synthesis. This suggests that the gut microbiota play a beneficial role in improving BA metabolism through Trp. Furthermore, fexaramine (a gut-specific FXR agonist) reversed the therapeutic effects of Trp, suggesting that Trp acts through the FXR signaling pathway. Finally, validation in a finishing pig model revealed that Trp improved lipid metabolism, enlarged the hepatic BA pool, and altered numerous glycerophospholipid molecules in the hepatic lipid profile. Conclusion: Our studies suggest that Trp inhibits intestinal FXR signaling mediated by the gut microbiota-BA crosstalk, which in turn promotes hepatic BA synthesis, thereby ameliorating MS.}, }
@article {pmid39679259, year = {2024}, author = {Feng, M and Zou, Z and Shou, P and Peng, W and Liu, M and Li, X}, title = {Gut microbiota and Parkinson's disease: potential links and the role of fecal microbiota transplantation.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1479343}, pmid = {39679259}, issn = {1663-4365}, abstract = {Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and seriously affects the quality of life of elderly patients. PD is characterized by the loss of dopaminergic neurons in the substantia nigra as well as abnormal accumulation of α-synuclein in neurons. Recent research has deepened our understanding of the gut microbiota, revealing that it participates in the pathological process of PD through the gut-brain axis, suggesting that the gut may be the source of PD. Therefore, studying the relationship between gut microbiota and PD is crucial for improving our understanding of the disease's prevention, diagnosis, and treatment. In this review, we first describe the bidirectional regulation of the gut-brain axis by the gut microbiota and the mechanisms underlying the involvement of gut microbiota and their metabolites in PD. We then summarize the different species of gut microbiota found in patients with PD and their correlations with clinical symptoms. Finally, we review the most comprehensive animal and human studies on treating PD through fecal microbiota transplantation (FMT), discussing the challenges and considerations associated with this treatment approach.}, }
@article {pmid39677507, year = {2024}, author = {Li, Y and Xiao, P and Ding, H and Wang, H and Xu, Q and Wang, R and Zheng, L and Song, X and Wang, Y and Zhang, T}, title = {Fecal Microbiota Transplantation in Children with Autism.}, journal = {Neuropsychiatric disease and treatment}, volume = {20}, number = {}, pages = {2391-2400}, pmid = {39677507}, issn = {1176-6328}, abstract = {PURPOSE: This research aimed to explore the clinical efficacy of fecal microbiota transplantation (FMT) in treating children with autism spectrum disorder (ASD).<br><br>METHODS: In this single-arm prospective study, every participant received FMT therapy, followed by an 8-week follow-up. Children unable to swallow lyophilized capsules (Caps) received fecal solution through transendoscopic enteral tube (TET) or nasal jejunal tube (NJT) approaches. All participants underwent assessments of ASD core symptoms, gastrointestinal (GI) symptoms and sleep status initially, after treatment and during follow-up. The study outcomes included the changes in scores of the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Gastrointestinal Symptoms Rating Scale (GSRS) and Sleep Disturbance Scale for Children (SDSC), as well as the adverse events (AEs).<br><br>RESULTS: 98 participants were involved, consisting of 80 males and 18 females, with a median age of 7 years. 73 children received the FMT in the form of Caps, while 13 patients underwent the procedure through TET and 12 patients via NJT. Improvements were observed in all outcome measures for Caps and NJT groups at both the post-treatment and 8-week follow-up evaluations. Adjusted between-group analyses at post-treatment and follow-up showed that Caps and NJT group had greater reduction in ABC, CARS and SRS scores compared with TET group, while NJT group had greater reduction in SDSC scores compared with Caps and TET group. The incidence of AEs was 8.2% in the Caps group, 23.1% in the TET group, and 8.3% in the NJT group, with no serious AEs reported.<br><br>CONCLUSION: FMT treatment can improve the core symptoms, GI symptoms and sleep disturbances in children with ASD. The upper GI tract routes, including Caps and NJT, may be more effective and safe compared to the lower GI tract route of TET.}, }
@article {pmid39674485, year = {2025}, author = {Ni, Z and Chen, L and Qian, X and Yong, Y and Wu, M and Li, Y and Li, J and Wang, Y and Li, L and Shao, Y and Chen, A}, title = {Preliminary characterization of Ramaria botrytoides polysaccharide RB-P1-1 and analysis of its hypoglycemic effects by altering the gut microbiota and metabolites in mice with type 2 diabetes mellitus.}, journal = {International journal of biological macromolecules}, volume = {289}, number = {}, pages = {138774}, doi = {10.1016/j.ijbiomac.2024.138774}, pmid = {39674485}, issn = {1879-0003}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Diabetes Mellitus, Type 2/drug therapy/microbiology/metabolism ; Animals ; *Hypoglycemic Agents/pharmacology/chemistry/therapeutic use ; Mice ; Male ; *Polysaccharides/pharmacology/chemistry ; *Diabetes Mellitus, Experimental/drug therapy/microbiology/metabolism ; }, abstract = {Gut microbiota has a symbiotic relationship with the host and is closely linked to the development of type 2 diabetes mellitus (T2DM). Polysaccharides are natural bioactive compounds with beneficial effects on T2DM; however, the mechanisms underlying their effects remain unclear. This study investigated the hypoglycemic effects of a purified polysaccharide, RB-P1-1, from Ramaria botrytoides and assessed its association with gut microbiota and metabolite changes using 16S rDNA sequencing and liquid chromatography-mass spectrometry, respectively. Hypoglycemic effects were evaluated after microbial community restoration via fecal microbiota transplantation. RB-P1-1 significantly improved hyperglycemia profiles and reshaped gut microbiota, increasing the abundance of Alistipes, Bacteroides, Ruminococcus, Odoribacter, Akkermansia, and Turicibacter. RB-P1-1 modulated microbiota metabolites associated with hypoglycemic effects, including pyridoxamine, L-histidine, quercetin, 3-phosphonopropionic acid, oleoylethanolamide, 3-ketocholanic acid, 4-phenylbutyric acid, LysoPC(P-16:0/0:0), LysoPC(18:2), and short-chain fatty acids, and altered various metabolic pathways involved in T2DM development. Gut microbiota that showed altered abundance were correlated with metabolites that showed altered concentration. Gut microbiota isolated from the RB-P1-1-treated group alleviated the symptoms associated with T2DM. These results suggest RB-P1-1 is an effective active ingredient in the treatment of T2DM by modulating gut microbiota and metabolites.}, }
@article {pmid39674267, year = {2025}, author = {Cheng, X and Yang, J and Wang, Z and Zhou, K and An, X and Xu, ZZ and Lu, H}, title = {Modulating intestinal viruses: A potential avenue for improving metabolic diseases with unresolved challenges.}, journal = {Life sciences}, volume = {361}, number = {}, pages = {123309}, doi = {10.1016/j.lfs.2024.123309}, pmid = {39674267}, issn = {1879-0631}, mesh = {Animals ; *Metabolic Diseases/virology/therapy ; *Gastrointestinal Microbiome ; Humans ; *Virome ; Fecal Microbiota Transplantation/methods ; Mice ; Intestines/microbiology/virology ; Viruses ; Feces/virology/microbiology ; }, abstract = {The gut microbiome affects the occurrence and development of metabolic diseases, with a significant amount of research focused on intestinal bacteria. As an important part of the gut microbiome, gut viruses were studied recently, particularly through fecal virome transplantation (FVT), revealing manipulating the gut virus could reverse overweight and glucose intolerance in mice. And human cohort studies found gut virome changed significantly in patients with metabolic disease. By summarizing those studies, we compared the research and analytical methods, as well as the similarities and differences in their results, and analyzed the reasons for these discrepancies. FVT provided potential value to improve metabolic diseases, but the mechanisms involved and the effect of FVT on humans should be investigated further. The potential methods of regulating intestinal virome composition and the possible mechanisms of intestinal virome changes affecting metabolic diseases were also discussed.}, }
@article {pmid39672770, year = {2025}, author = {Facchin, S and Cardin, R and Patuzzi, I and Carlotto, C and Minotto, M and Barberio, B and Zingone, F and Besutti, VM and Castagliuolo, I and Cattelan, A and Savarino, EV}, title = {Long-term stability and efficacy of frozen fecal microbiota transplant (FMT) product at 24 months.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {57}, number = {3}, pages = {702-706}, doi = {10.1016/j.dld.2024.11.025}, pmid = {39672770}, issn = {1878-3562}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Feces/microbiology ; Male ; Female ; Middle Aged ; *Freezing ; *Clostridium Infections/therapy ; Aged ; Clostridioides difficile ; Treatment Outcome ; Adult ; *Cryopreservation ; Gastrointestinal Microbiome ; Time Factors ; }, abstract = {BACKGROUND: Freezing donor fecal microbiota has improved fecal microbiota transplantation (FMT) for recurrent C. difficile infection (CDI), achieving short-term effectiveness similar to fresh-samples. Research shows frozen fecal matter remains effective for up to 12-months at -80 °C.<br><br>OBJECTIVE: To assess how long-term-freezing and thawing affect the viability, microbial composition, and clinical efficacy of frozen-stools for FMT.<br><br>METHODS: Stool samples from three donors were processed into 18 aliquots, thawed at intervals over two years, and analyzed for cell viability and microbial load. Microbiota composition was assessed through 16S-sequencing, with diversity evaluated using the Shannon-index and Principal-Coordinates-Analysis based on Bray-Curtis-distance (&#x3b1;/&#x3b2;-diversity). The same donors provided fecal material for a total of 23 FMT procedures, including 15 for CDI and 8 off-label.<br><br>RESULTS: We found that donor stools frozen for two years contained viable bacteria comparable to fresh samples, with anaerobic and aerobic species remaining viable for 24 months. Despite a reduction in colony-forming-units, FMT was successful in 71.4 % and 100 % of the cases at one year and at the end of follow-up, respectively. Most bacterial changes occurred among anaerobic species (Blautia producta and Bifidobacterium adolescentis), increasing post-thawing. Notably, specific taxa, (C. aerofaciens and Erysipelotrichaceae_Cc115), showed significant unexplained increase.<br><br>CONCLUSION: Long-term-stool-storage enhances FMT accessibility without compromising its success, despite taxonomic changes after 24 months.}, }
@article {pmid39672439, year = {2025}, author = {Chen, P and Chen, F and Hou, T and Hu, X and Xia, C and Zhang, J and Shen, S and Li, C and Li, K}, title = {Administration time modify the anxiolytic and antidepressant effects of inulin via gut-brain axis.}, journal = {International journal of biological macromolecules}, volume = {288}, number = {}, pages = {138698}, doi = {10.1016/j.ijbiomac.2024.138698}, pmid = {39672439}, issn = {1879-0003}, mesh = {*Inulin/pharmacology/administration &amp; dosage ; Animals ; *Anti-Anxiety Agents/pharmacology/administration &amp; dosage ; *Antidepressive Agents/pharmacology/administration &amp; dosage ; Male ; *Gastrointestinal Microbiome/drug effects ; *Brain/drug effects/metabolism ; Mice ; Anxiety/drug therapy ; Depression/drug therapy ; Fecal Microbiota Transplantation ; Time Factors ; *Brain-Gut Axis/drug effects ; Behavior, Animal/drug effects ; }, abstract = {An imbalance in the microbiota-gut-brain axis exerts an essential effect on the pathophysiology of depressive and anxiety disorders. Our previous research revealed that the timing of inulin administration altered its effects on chronic unpredictable mild stress (CUMS)-induced anxiety and depression. However, it is still unclear if the gut-brain axis is primarily responsible for these effects. In this study, fecal microbiota transplantation (FMT) confirmed that inulin administration at different times alleviated CUMS-induced anxiety- and depression-like behaviors via the gut-brain axis. The time of administration seemed to modify the anxiolytic and antidepressant effects of inulin, and inulin intervention in the evening was more pronounced in inhibiting the inflammatory responses than that of morning inulin intervention. Serum metabolomics analysis showed that the main differential metabolites, including fenofibric acid, 4'-Hydroxyfenoprofen glucuronide and 5-(4-Hydroxybenzyl)thiazolidine-2,4-dione may be vital for the anxiolytic and antidepressant effects of different inulin treatment times. Our results suggested that inulin administration in the evening was more effective in alleviating the inflammatory responses and improving amino acids metabolism. This study provides a new potential link between the microbiota-gut-brain axis and chrono-nutrition, demonstrating that a more appropriate administration time results in a better intervention effect.}, }
@article {pmid39672393, year = {2025}, author = {He, P and He, H and Su, C and Liu, Y and Wang, J and Wu, Y and Wang, B and Wang, S and Zhao, J}, title = {Amomum villosum Lour. alleviates pre-eclampsia by inducing enrichment of Bifidobacterium bifidum through vanillic acid to inhibit placental ferroptosis.}, journal = {Journal of ethnopharmacology}, volume = {340}, number = {}, pages = {119217}, doi = {10.1016/j.jep.2024.119217}, pmid = {39672393}, issn = {1872-7573}, mesh = {Pregnancy ; Female ; Animals ; *Pre-Eclampsia/drug therapy/prevention &amp; control ; *Placenta/drug effects/metabolism ; Gastrointestinal Microbiome/drug effects ; Mice ; *Ferroptosis/drug effects ; *Vanillic Acid/pharmacology/metabolism ; *Bifidobacterium/drug effects ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Amomum villosum Lour. (AVL), a traditional Chinese medicine, is widely used to pregnancy-related vomiting and prevent miscarriage. Pre-eclampsia (PE) is a severe pregnancy syndrome. Recent studies have demonstrated interactions between PE and the digestive system. However, it is uncertain that AVL against PE was associated with the gut.<br><br>AIM OF THE STUDY: The current research examined the curative impact of AVL on PE and underly mechanisms based on the gut-placenta axis.<br><br>MATERIALS AND METHODS: A water decoction of AVL (WOA) was extracted in boiling water, and then the decoction was converted into dried particles by freeze drying. An NG-nitro-L-arginine methyl ester (L-NAME)-induced PE mouse model was established and the preventative activity of WOA was evaluated. Furthermore, the gut microbial composition and structure were analyzed using 16S rRNA gene sequencing. Fecal microbiota transplantation (FMT) experiment was applied to confirm the efficacy of gut microbiota remodeled by WOA.<br><br>RESULTS: WOA presented protective efficacy against PE. Notably, WOA induced a significant decrease in maternal hypertension and urine protein levels and promoted fetal intrauterine growth in a dose-dependent manner, thereby improving adverse pregnancy outcomes. Moreover, WOA modulated the angiogenic imbalance by decreasing the ratio between sFlt-1 (soluble fms-like tyrosine kinase 1) and PlGF (placental growth factor) to repair placental injury and inhibited placental ferroptosis by increasing the protein levels of FPN1, FTH1, xCT, and GPX4. Tight junction proteins (ZO-1, Occludin, Claudin1) in the placenta and colon were significantly upregulated by WOA, leading to enhanced placental and gut barriers. WOA rescued intestinal dysbiosis by enriching Bifidobacterium and Akkermansia. Fecal microbiota transplantation (FMT) experiments revealed that the protection of WOA on placenta and gut were dependent on the gut microbial composition. Furthermore, supplementation with both Bifidobacterium bifidum (B. bifidum) and vanillic acid (VA, the major component of WOA) ameliorated PE symptoms. Intriguingly, results from both in vivo and in vitro analyses indicated that the B. bifidum population was enriched by VA.<br><br>CONCLUSIONS: This research is the first to demonstrate that WOA prevents PE by enriching Bifidobacterium bifidum, strengthening the gut-placenta barrier, and inhibiting placental ferroptosis. Our findings provide compelling evidence for the vital involvement of the gut-placental axis in the protection of AVL on PE, presenting a novel target for the clinic.}, }
@article {pmid39671402, year = {2024}, author = {, }, title = {Retraction: Fecal microbiota transplantation for treatment of recurrent C. difficile infection: An updated randomized controlled trial meta-analysis.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0316040}, pmid = {39671402}, issn = {1932-6203}, }
@article {pmid39670752, year = {2025}, author = {Peterson, D and Weidenmaier, C and Timberlake, S and Gura Sadovsky, R}, title = {Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease.}, journal = {Microbiology spectrum}, volume = {13}, number = {2}, pages = {e0199924}, pmid = {39670752}, issn = {2165-0497}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/metabolism ; *Gastrointestinal Microbiome ; *Bile Acids and Salts/metabolism ; Feces/microbiology ; *Bacteria/metabolism/genetics/classification/isolation &amp; purification ; Operon ; Metagenomics ; Female ; Clostridium/genetics/metabolism ; Male ; Metagenome ; Adult ; }, abstract = {The gut microbiome plays a key role in bile acid (BA) metabolism, where a diversity of metabolic products contribute to human health and disease. In particular, Inflammatory Bowel Disease (IBD) is characterized by a low concentration of secondary bile acids (SBAs), whose transformation from primary bile acids (PBAs) is an essential function performed solely by gut bacteria. BA-transformation activity mediated by the bile acid inducible (bai) operon has been functionally characterized in the genus Clostridium, and homologous bai gene sequences have been found in metagenome-assembled genomes (MAGs) belonging to other taxa in the human gut, but it is unclear which species of bai-carrying bacteria perform physiologically significant amounts of bile acid transformation in healthy and sick individuals. Here, we analyzed hundreds of stool samples with paired metagenomic and metabolomic data from IBD patients and controls and found that the abundance of the bai operon in metagenomic samples was highly predictive of that sample's high- or low-SBA metabolic state. We further found that bai genes from the Clostridium species best characterized as BA transformers were more prevalent in IBD patients than in non-IBD controls, while bai genes from uncharacterized taxa known only from MAGs were much more physiologically relevant in non-IBD samples. These un-isolated clades of BA-transforming bacteria merit further research; as beyond their prevalence in the human population, we found some cases in which they engrafted in IBD patients who had undergone fecal microbiota transplantation and experienced a clinical response.IMPORTANCEIn this paper, we identify specific bacteria that perform an important metabolic function in the human gut and demonstrate that in the guts of a large subset of patients with IBD, these bacteria are missing and the function is defective. This is a rare example where the correlation between the absence of specific bacteria and the dysfunction of metabolism is directly observed, not in mice nor in the lab, but in physiologic microbial communities in the human gut. Our results point to a path for studying how a small but important set of bacteria is affected by conditions in the IBD gut and perhaps to the development of interventions to mitigate the loss of these bacteria in IBD.}, }
@article {pmid39669573, year = {2024}, author = {Yan, J and Yang, L and Ren, Q and Zhu, C and Du, H and Wang, Z and Qi, Y and Xian, X and Chen, D}, title = {Gut microbiota as a biomarker and modulator of anti-tumor immunotherapy outcomes.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1471273}, pmid = {39669573}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/therapy/immunology ; *Immunotherapy/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; Animals ; Biomarkers, Tumor ; Probiotics/therapeutic use ; Treatment Outcome ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; }, abstract = {Although immune-checkpoint inhibitors (ICIs) have significantly improved cancer treatment, their effectiveness is limited by primary or acquired resistance in many patients. The gut microbiota, through its production of metabolites and regulation of immune cell functions, plays a vital role in maintaining immune balance and influencing the response to cancer immunotherapies. This review highlights evidence linking specific gut microbial characteristics to increased therapeutic efficacy in a variety of cancers, such as gastrointestinal cancers, melanoma, lung cancer, urinary system cancers, and reproductive system cancers, suggesting the gut microbiota's potential as a predictive biomarker for ICI responsiveness. It also explores the possibility of enhancing ICI effectiveness through fecal microbiota transplantation, probiotics, prebiotics, synbiotics, postbiotics, and dietary modifications. Moreover, the review underscores the need for extensive randomized controlled trials to confirm the gut microbiota's predictive value and to establish guidelines for microbiota-targeted interventions in immunotherapy. In summary, the article suggests that a balanced gut microbiota is key to maximizing immunotherapy benefits and calls for further research to optimize microbiota modulation strategies for cancer treatment. It advocates for a deeper comprehension of the complex interactions between gut microbiota, host immunity, and cancer therapy, aiming for more personalized and effective treatment options.}, }
@article {pmid39668679, year = {2025}, author = {Vitarelli, A and Minafra, P and Vulpi, M and Piana, A and Torre, G and Carbonara, U and Divenuto, L and Papapicco, G and Chiaradia, F and Alba, S and Lucarelli, G and Battaglia, M and Ditonno, P}, title = {A new approach to repair recurrent vescicourethral anastomotic strictures after radical prostatectomy: The use of prerectal access.}, journal = {Urologia}, volume = {92}, number = {2}, pages = {335-341}, doi = {10.1177/03915603241300877}, pmid = {39668679}, issn = {1724-6075}, mesh = {Humans ; Male ; *Prostatectomy/adverse effects ; Anastomosis, Surgical/adverse effects ; Aged ; *Postoperative Complications/surgery/etiology ; Middle Aged ; *Urethra/surgery ; Recurrence ; *Urinary Bladder/surgery ; *Urethral Stricture/surgery/etiology ; Prostatic Neoplasms/surgery ; Constriction, Pathologic/surgery/etiology ; }, abstract = {BACKGROUND: Vesicourethral anastomosis stenosis (VUAS) is a well-known complication of prostate cancer treatments, observed in up to 26% of the cases after radical prostatectomy. Conservative management, with single or even repeated transurethral dilation or endoscopic incision of the stenosis, is successful in many cases, but up to 9% of patients are destined to fail after endoscopic treatment. In these cases, a revision of the vesicourethral anastomosis is necessary and can be realized with different surgical approaches. We aim to describe the technique and the outcomes of a new prerectal approach for VUAS repair.<br><br>METHODS: Twelve patients with recalcitrant VUAS following radical prostatectomy were enrolled between May 2014 and September 2018 for prerectal transperineal re-anastomosis. The evaluated outcomes were: the rate of successful anatomical repair at 3&#x2009;months after surgery and at the last follow-up, postoperative incontinence and complications rate, and the need for further treatments.<br><br>RESULTS: No major intraoperative complications occurred. After a median follow-up of 46&#x2009;months (IQR 36-55), 10 patients (83.3%) achieved a good anatomical repair even if one man required an endoscopic urethrotomy, while two patients (16.67%) with a history of pelvic radiotherapy developed a surgical site infection that required toilette and external urinary diversion. Among the others, nine (75%) developed severe stress urinary incontinence, with resolution of their condition. No patient reported significant postoperative pain or fecal incontinence.<br><br>CONCLUSIONS: The prerectal approach to VUAS repair allows direct access to the posterior urethra and the anastomosis, providing a better mobilization of the bladder neck for tension-free anastomosis. However, patients with a history of pelvic radiotherapy have a higher risk of complications. Postoperative incontinence is very common, but urinary continence could be restored with subsequent artificial urinary sphincter placement.}, }
@article {pmid39667939, year = {2025}, author = {Dang, H and Feng, P and Zhang, S and Peng, L and Xing, S and Li, Y and Wen, X and Zhou, L and Goswami, S and Xiao, M and Barker, N and Sansonetti, P and Kundu, P}, title = {Maternal gut microbiota influence stem cell function in offspring.}, journal = {Cell stem cell}, volume = {32}, number = {2}, pages = {246-262.e8}, doi = {10.1016/j.stem.2024.10.003}, pmid = {39667939}, issn = {1875-9777}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Female ; Mice ; Pregnancy ; *Stem Cells/cytology/metabolism ; Mice, Inbred C57BL ; TOR Serine-Threonine Kinases/metabolism ; Cell Differentiation ; Male ; Fatty Acids, Volatile/metabolism ; Cell Proliferation ; Akkermansia ; }, abstract = {The maternal microbiome influences child health. However, its impact on a given offspring's stem cells, which regulate development, remains poorly understood. To investigate the role of the maternal microbiome in conditioning the offspring's stem cells, we manipulated maternal microbiota using Akkermansia muciniphila. Different maternal microbiomes had distinct effects on proliferation and differentiation of neuronal and intestinal stem cells in the offspring, influencing their developmental trajectory, physiology, and long-term health. Transplantation of altered maternal microbiota into germ-free mice transmitted these stem cell phenotypes to the recipients' offspring. The progeny of germ-free mice selectively colonized with Akkermansia did not display these stem cell traits, emphasizing the importance of microbiome diversity. Metabolically more active maternal microbiomes enriched the levels of circulating short-chain fatty acids (SCFAs) and amino acids, leaving distinct transcriptomic imprints on the mTOR pathway of offsprings' stem cells. Blocking mTOR signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of the maternal microbiome in programming offsprings' stem cells and represent a promising target for interventions.}, }
@article {pmid39667762, year = {2025}, author = {Zhang, QW and Yang, MJ and Liao, CY and Taha, R and Li, QY and Abdelmotalab, MI and Zhao, SY and Xu, Y and Jiang, ZZ and Chu, CH and Huang, X and Jiao, CH and Sun, LX}, title = {Atractylodes macrocephala Koidz polysaccharide ameliorates DSS-induced colitis in mice by regulating the gut microbiota and tryptophan metabolism.}, journal = {British journal of pharmacology}, volume = {182}, number = {7}, pages = {1508-1527}, doi = {10.1111/bph.17409}, pmid = {39667762}, issn = {1476-5381}, support = {82074115//National Natural Science Foundation of China/ ; 82174072//National Natural Science Foundation of China/ ; JSPH-MB-2022-2 supporting//Clinical Capability Enhancement Project Medical/ ; JSPH-MB-2022-2//Clinical Capability Enhancement Project/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Tryptophan/metabolism ; *Atractylodes/chemistry ; Mice ; *Polysaccharides/pharmacology/therapeutic use/isolation &amp; purification ; *Colitis/drug therapy/chemically induced/metabolism/microbiology ; Dextran Sulfate ; Mice, Inbred C57BL ; Male ; Receptors, Aryl Hydrocarbon/metabolism ; }, abstract = {BACKGROUND AND PURPOSE: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS-induced colitis, and we aimed to investigate the underlying mechanisms in this study.<br><br>EXPERIMENTAL APPROACH: PAMK was used to treat DSS-induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan-metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic-mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis.<br><br>KEY RESULTS: PAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan-metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance.<br><br>CONCLUSION AND IMPLICATIONS: Based on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS-induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.}, }
@article {pmid39667450, year = {2025}, author = {Fu, Q and Yang, Y and Tian, Q and Zhu, Y and Xu, H and Wang, J and Huang, Q}, title = {Exploring the mechanism of Paotianxiong polysaccharide in the treatment of chronic kidney disease combining metabolomics and microbiomics technologies.}, journal = {International journal of biological macromolecules}, volume = {289}, number = {}, pages = {138629}, doi = {10.1016/j.ijbiomac.2024.138629}, pmid = {39667450}, issn = {1879-0003}, mesh = {Animals ; *Renal Insufficiency, Chronic/drug therapy/metabolism/microbiology ; *Metabolomics/methods ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/pharmacology/therapeutic use/chemistry ; Rats ; Male ; Kidney/drug effects ; Rats, Sprague-Dawley ; Fecal Microbiota Transplantation ; Disease Models, Animal ; }, abstract = {A close relationship between the pathogenesis of chronic kidney disease (CKD) and abnormalities in the gut-kidney axis. Paotianxiong polysaccharides (PTXP) that have demonstrated therapeutic effects on CKD. However, the specific mechanism by which PTXP ameliorates CKD through the gut-kidney axis remains to be explored. In this study, the microbiomes and metabolomics were combined to investigate the impact of PTXP on intestinal flora structure and metabolism, further unveiling the relationship through correlation analysis. The results showed that PTXP intervention significantly modulated renal function abnormalities in CKD rats and significantly modulates gut microbial disorders, evidenced by an increased abundance of Lactobacillus murinus, Bacteroides fragilis, and a decreased abundance of Bifidobacterium pseudolongum. Furthermore, PTXP reversed the changes in intestinal metabolites, such as linoleic acid and docosahexaenoic acid, induced by CKD and identified unsaturated fatty acid metabolism as a key metabolic pathway. Correlation analyses also revealed associations among gut microorganisms, metabolites, and renal function indexes, confirming that PTXP alleviated CKD through the gut-kidney axis. Moreover, the above conclusions were verified by fecal bacteria transplantation experiments. These findings provide insights into the mechanism of PTXP for the treatment of CKD and provide new targets for the treatment of CKD.}, }
@article {pmid39666007, year = {2025}, author = {Shang, J and Del Valle, DM and Britton, GJ and Mead, KR and Rajpal, U and Chen-Liaw, A and Mogno, I and Li, Z and Menon, R and Gonzalez-Kozlova, E and Elkrief, A and Peled, JU and Gonsalves, TR and Shah, NJ and Postow, M and Colombel, JF and Gnjatic, S and Faleck, DM and Faith, JJ}, title = {Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis.}, journal = {The Journal of experimental medicine}, volume = {222}, number = {1}, pages = {}, pmid = {39666007}, issn = {1540-9538}, support = {U24 CA224319/CA/NCI NIH HHS/United States ; U01 DK124165/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; F30 CA261144/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K08HL143189/NH/NIH HHS/United States ; //Memorial Sloan-Kettering Cancer Center/ ; P30 CA196521/CA/NCI NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/immunology/drug effects ; Animals ; Humans ; *Colitis/microbiology/immunology/chemically induced ; Mice ; *Immunotherapy/adverse effects/methods ; Female ; Male ; Immune Checkpoint Inhibitors/adverse effects/pharmacology ; Mice, Inbred C57BL ; Middle Aged ; Aged ; Feces/microbiology ; Neoplasms/immunology/microbiology/therapy/drug therapy ; }, abstract = {Immunotherapy-related colitis (irC) frequently emerges as an immune-related adverse event during immune checkpoint inhibitor therapy and is presumably influenced by the gut microbiota. We longitudinally studied microbiomes from 38 ICI-treated cancer patients. We compared 13 ICI-treated subjects who developed irC against 25 ICI-treated subjects who remained irC-free, along with a validation cohort. Leveraging a preclinical mouse model, predisease stools from irC subjects induced greater colitigenicity upon transfer to mice. The microbiota during the first 10 days of irC closely resembled inflammatory bowel disease microbiomes, with reduced diversity, increased Proteobacteria and Veillonella, and decreased Faecalibacterium, which normalized before irC remission. These findings highlight the irC gut microbiota as functionally distinct but phylogenetically similar to non-irC and healthy microbiomes, with the exception of an acute, transient disruption early in irC. We underscore the significance of longitudinal microbiome profiling in developing clinical avenues to detect, monitor, and mitigate irC in ICI therapy cancer patients.}, }
@article {pmid39664442, year = {2024}, author = {Chen, L and Zhang, K and Liu, J and Li, X and Liu, Y and Ma, H and Yang, J and Li, J and Chen, L and Hsu, C and Zeng, J and Xie, X and Wang, Q}, title = {The role of the microbiota-gut-brain axis in methamphetamine-induced neurotoxicity: Disruption of microbial composition and short-chain fatty acid metabolism.}, journal = {Acta pharmaceutica Sinica. B}, volume = {14}, number = {11}, pages = {4832-4857}, pmid = {39664442}, issn = {2211-3835}, abstract = {Methamphetamine (METH) abuse is associated with significant neurotoxicity, high addiction potential, and behavioral abnormalities. Recent studies have identified a connection between the gut microbiota and METH-induced neurotoxicity and behavioral disorders. However, the underlying causal mechanisms linking the gut microbiota to METH pathophysiology remain largely unexplored. In this study, we employed fecal microbiota transplantation (FMT) and antibiotic (Abx) intervention to manipulate the gut microbiota in mice administered METH. Furthermore, we supplemented METH-treated mice with short-chain fatty acids (SCFAs) and pioglitazone (Pio) to determine the protective effects on gut microbiota metabolism. Finally, we assessed the underlying mechanisms of the gut-brain neural circuit in vagotomized mice. Our data provide compelling evidence that modulation of the gut microbiome through FMT or microbiome knockdown by Abx plays a crucial role in METH-induced neurotoxicity, behavioral disorders, gut microbiota disturbances, and intestinal barrier impairment. Furthermore, our findings highlight a novel prevention strategy for mitigating the risks to both the nervous and intestinal systems caused by METH, which involves supplementation with SCFAs or Pio.}, }
@article {pmid39664063, year = {2024}, author = {Li, L and Cai, F and Guo, C and Liu, Z and Qin, J and Huang, J}, title = {Gut microbiome and NAFLD: impact and therapeutic potential.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1500453}, pmid = {39664063}, issn = {1664-302X}, abstract = {Non-Alcoholic Fatty Liver Disease (NAFLD) affects approximately 32.4% of the global population and poses a significant health concern. Emerging evidence underscores the pivotal role of the gut microbiota-including bacteria, viruses, fungi, and parasites-in the development and progression of NAFLD. Dysbiosis among gut bacteria alters key biological pathways that contribute to liver fat accumulation and inflammation. The gut virome, comprising bacteriophages and eukaryotic viruses, significantly shapes microbial community dynamics and impacts host metabolism through complex interactions. Similarly, gut fungi maintain a symbiotic relationship with bacteria; the relationship between gut fungi and bacteria is crucial for overall host health, with certain fungal species such as Candida in NAFLD patients showing detrimental associations with metabolic markers and liver function. Additionally, the "hygiene hypothesis" suggests that reduced exposure to gut parasites may affect immune regulation and metabolic processes, potentially influencing conditions like obesity and insulin resistance. This review synthesizes current knowledge on the intricate interactions within the gut microbiota and their associations with NAFLD. We highlight the therapeutic potential of targeting these microbial communities through interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Addressing the complexities of NAFLD requires comprehensive strategies that consider the multifaceted roles of gut microorganisms in disease pathology.}, }
@article {pmid39664050, year = {2024}, author = {Alhamlan, FS and Albadawi, IA and Al-Qahtani, AA and Awartani, KA and Obeid, DA and Tulbah, AM}, title = {Cervicovaginal and gastrointestinal microbiomes in gynecological cancers and their roles in therapeutic intervention.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1489942}, pmid = {39664050}, issn = {1664-302X}, abstract = {Cancer remains a significant global health concern, and understanding factors that regulate cancer development is important. The microbiome, with its potential role in cancer development, progression, and treatment, has garnered increasing attention in recent years. The cervicovaginal and gastrointestinal microbiomes in females constitute complex biological ecosystems. Although the gut microbiome has been extensively studied, little is known about the cervicovaginal microbiome. The microbiome plays a crucial role in maintaining local microenvironments and tissue homeostasis, but dysbiosis can disrupt this fine balance and contribute to pathological ramifications leading to cancer. This review explores the current understanding of the microbiome's correlation with gynecological cancers and highlights the potential of microbiome-based interventions to improve outcomes in these cancers. In addition, this review underscores the gaps and limitations in the literature, such as findings in specific ethnicities compared with understudied ethnicities. In addition, discrepancies in molecular techniques and terminology (microbiome vs. microbiota) used in the literature are addressed. Emerging evidence linking gynecological cancers and dysbiosis underscores microbiota as a potential target for cancer prevention and therapy. Manipulating the microbiome, such as through the use of probiotics, prebiotics, antibiotics, or vaginal and fecal transplantation, has demonstrated benefits in the treatment of chronic and inflammatory conditions. Further translational research in this field is needed to integrate the benefits of beneficial microorganisms in the fight against gynecological cancers.}, }
@article {pmid39662821, year = {2025}, author = {Groenewegen, B and van Lingen, E and Kovynev, A and van den Berg, AJ and Berssenbrugge, EKL and Sanders, IMJG and van Prehn, J and van Nood, E and Goorhuis, A and Kuijper, EJ and Smits, WK and Wiese, M and Keller, JJ and Ducarmon, QR and Terveer, EM and , }, title = {The presence of Clostridioides difficile in faeces before and after faecal microbiota transplantation and its relation with recurrent C. difficile infection and the gut microbiota in a Dutch cohort.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {31}, number = {4}, pages = {568-574}, doi = {10.1016/j.cmi.2024.12.003}, pmid = {39662821}, issn = {1469-0691}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridioides difficile/isolation &amp; purification/genetics ; *Feces/microbiology ; Male ; *Clostridium Infections/therapy/microbiology/epidemiology ; Female ; Middle Aged ; Aged ; *Gastrointestinal Microbiome ; Recurrence ; Netherlands/epidemiology ; Adult ; Cohort Studies ; Anti-Bacterial Agents/therapeutic use ; Aged, 80 and over ; Risk Factors ; Vancomycin/therapeutic use ; Treatment Outcome ; }, abstract = {OBJECTIVES: The objectives of this study are to investigate the presence of Clostridioides difficile in faeces of patients with recurrent C. difficile infection (rCDI) before and after faecal microbiota transplantation (FMT) and to identify risk factors for faecal C. difficile and C. difficile infection (CDI) recurrence.<br><br>METHODS: n&#xa0;=&#xa0;83 faecal sample triads (pre-FMT [&#x223c;1&#xa0;day], post-FMT [&#x223c;3&#xa0;weeks], and a corresponding FMT donor sample), and n&#xa0;=&#xa0;22 long-term (&#x223c;1-3&#xa0;years) follow-up faecal samples were collected from FMT-treated patients. The presence of C.&#xa0;difficile in faeces was assessed by enrichment broth culture and PCR (tcdB gene) and associated with patient characteristics, FMT outcome, duration of pre-FMT vancomycin, FMT donor, post-FMT antibiotic use, and faecal microbiota composition (shotgun metagenomics).<br><br>RESULTS: The FMT cure rate for rCDI was 92.8% (77/83), with six early CDI recurrences (<2&#xa0;months post-FMT). Toxigenic C.&#xa0;difficile was cultured in 27.7% (23/83) of all patients post-FMT, 23.4% (18/77) of patients cured 2&#xa0;months post-FMT, and 13.6% (3/22) at long-term follow-up. Early CDI recurrence (n&#xa0;=&#xa0;6) was associated with positive C.&#xa0;difficile culture post-FMT (21.7% [5/23] vs. 1.7% [1/60], p 0.01), post-FMT antibiotics (30.0% [3/10] vs. 4.6% [3/65], p 0.03), and a short course of pre-FMT vancomycin (median 6.0&#xa0;days, IQR [5-12] vs. 18&#xa0;days, IQR [10.8-29], p&#xa0;<&#xa0;0.05). Additionally, positive C.&#xa0;difficile culture directly pre-FMT was associated with a short course of pre-FMT vancomycin (median 9&#xa0;days IQR [5-18] vs. 17&#xa0;days, IQR [10-29.2], p 0.04). Gut microbiota analyses did not reveal signatures associated with C.&#xa0;difficile culture result, despite statistically non-significant trends in relative abundances of the Enterobacteriaceae family, and Dorea, Roseburia, and Clostridiales species.<br><br>DISCUSSION: Although eradication of C.&#xa0;difficile is not required for clinical cure of rCDI by FMT, it is associated with reduced prevalence of early CDI recurrence, as are the full completion of pre-FMT vancomycin (at least 10&#xa0;days) and avoiding post-FMT antibiotics.}, }
@article {pmid39659943, year = {2024}, author = {Zhao, W and Chen, Y and Xiao, J and Tang, Z and Wang, L and Ren, Y and Chen, Y}, title = {Updated outcomes and exploratory analysis of RENMIN-215: tislelizumab plus fruquintinib and fecal microbiota transplantation in refractory microsatellite stable metastatic colorectal cancer.}, journal = {American journal of cancer research}, volume = {14}, number = {11}, pages = {5351-5364}, pmid = {39659943}, issn = {2156-6976}, abstract = {Primary analysis of the open-label, single-arm, phase II RENMIN-215 trial (primary data cutoff date: July 10, 2023) showed promising efficacy and tolerable safety with tislelizumab plus fruquintinib and fecal microbiota transplantation (FMT) in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Here, we reported updated survival and safety results with a median follow-up of 34.0 months (data cut-off May 20, 2024), as well as patient-reported outcomes and laboratory analysis. Twenty patients with MSS mCRC resistant or refractory to at least second-line therapy were enrolled and received tislelizumab plus fruquintinib and FMT. The primary endpoint was progression-free survival. Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate, safety, health-related quality of life questionnaire and exploratory laboratory tests. In addition, 94 mCRC patients who received third-line or above immunotherapy in real world were screened for propensity score matching (PSM) analysis to compare efficacy. Our results showed that the median OS was 13.7 months (95% CI, 9.3-17.7), and the ORR was 20.0% (95% CI, 5.7-43.7). After PSM, the median OS benefit of the study regimen remained statistically significant (HR = 0.26; 95% CI, 0.07-0.95; P = 0.042). Patients with primary tumor surgery had better clinical outcomes. No new safety concerns were detected. Seven (35.0%) patients had one or more grade 3 treatment-related adverse events. The majority of patients had improved or stable global health status (GHS). Median time to deterioration for GHS was 7.7 months. Peripheral blood lymphocyte analysis showed that increased gamma-delta 2 T cells were positively associated with improved response and survival. To conclude, the updated results provide further evidence of sustained antitumor activity of tislelizumab plus fruquintinib and FMT in heavily pretreated MSS mCRC patients with a consistent safety profile.}, }
@article {pmid39659426, year = {2024}, author = {Abildinova, GZ and Benberin, VV and Vochshenkova, TA and Afshar, A and Mussin, NM and Kaliyev, AA and Zhussupova, Z and Tamadon, A}, title = {The gut-brain-metabolic axis: exploring the role of microbiota in insulin resistance and cognitive function.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1463958}, pmid = {39659426}, issn = {1664-302X}, abstract = {The gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic-pituitary-adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.}, }
@article {pmid39658705, year = {2024}, author = {Wang, Z and Wang, Z and Lu, T and Yuan, G and Chen, W and Jin, J and Jiang, X and Yan, W and Yuan, K and Zou, G and Bao, Y and Shi, J and Liu, X and Wei, H and Han, Y and Lu, L}, title = {Gut microbiota regulate insomnia-like behaviors via gut-brain metabolic axis.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {39658705}, issn = {1476-5578}, support = {82288101//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Sleep interacts reciprocally with the gut microbiota. However, mechanisms of the gut microbe-brain metabolic axis that are responsible for sleep behavior have remained largely unknown. Here, we showed that the absence of the gut microbiota can alter sleep behavior. Sleep deprivation reduced butyrate levels in fecal content and the hypothalamus in specific pathogen-free mice but not in germ-free mice. The microbial metabolite butyrate can promote sleep by modulating orexin neuronal activity in the lateral hypothalamic area in mice. Insomnia patients had lower serum butyrate levels and a deficiency in butyrate-producing species within the gut microbiota. Transplantation of the gut microbiota from insomnia patients to germ-free mice conferred insomnia-like behaviors, accompanied by a decrease in serum butyrate levels. The oral administration of butyrate rescued sleep disturbances in recipient mice. Overall, these findings reveal the causal role of microbial metabolic pathways in modulating insomnia-like behaviors, suggesting potential therapeutic strategies for treating sleep disorders.}, }
@article {pmid39658176, year = {2025}, author = {Guo, B and Zhang, W and Zhang, J and Zou, J and Dong, N and Liu, B}, title = {Euglena gracilis polysaccharide modulated gut dysbiosis of obese individuals via acetic acid in an in vitro fermentation model.}, journal = {Food research international (Ottawa, Ont.)}, volume = {199}, number = {}, pages = {115385}, doi = {10.1016/j.foodres.2024.115385}, pmid = {39658176}, issn = {1873-7145}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Dysbiosis ; *Fermentation ; *Acetic Acid/metabolism ; Humans ; *Obesity/metabolism/microbiology ; *Polysaccharides/pharmacology/metabolism ; *Euglena gracilis/metabolism ; Prebiotics ; Male ; Feces/microbiology ; Adult ; Bacteria/metabolism/classification/drug effects ; Lipid Metabolism/drug effects ; Female ; }, abstract = {Gut dysbiosis is a characteristic feature of obesity and targeting gut microbiota presents a promising approach to attenuate obesity. Euglena gracilis polysaccharide (EGP) has emerged as a potential prebiotic capable of promoting health-beneficial bacteria. However, its effects on the gut dysbiosis of obese individuals remain unclear. This study investigated the impacts of EGP on gut microbiota from both non-obese and obese individuals using an in vitro fermentation model. Results showed that EGP significantly altered the gut microbiota composition and metabolism. Specifically, EGP improved the relative abundance of Paeniclostridium, Clostridium_sensu_stricto_1 and Paraclostridium of the non-obese individuals and Providencia, Enterococcus and Bacteroides of the obese individuals. Metabolomics results showed EGP significantly altered the lipid metabolism especially in the obese group with enriched bile secretion and cholesterol metabolism pathways. Noting that acetic acid was significantly increased in both groups, these acetic acid favorable microbiota from non-obese individuals was collected with acetic acid supplementation. Transplantation of these acetic acid-induced microbiota (AAiM) notably improved the richness and diversity of fecal microbiota of the obese individuals, enhancing the growth of probiotics like Bacteroides and Bifidobacterium. Consequently, AAiM significantly restructured macronutrients (including amino acids, carbohydrates and lipids) metabolism of the gut microbiota from obese individuals. Altogether, this study underscores the potential of EGP and acetic acid favorable microbiota in manipulating obesity-associated gut dysbiosis via acetic acid production.}, }
@article {pmid39656490, year = {2024}, author = {Balakrishnan, R and Kang, SI and Lee, JY and Rho, YK and Kim, BK and Choi, DK}, title = {Gut Microbiota-Immune System Interactions in Health and Neurodegenerative Diseases: Insights into Molecular Mechanisms and Therapeutic Applications.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.1362}, pmid = {39656490}, issn = {2152-5250}, abstract = {The human body contains approximately 100 trillion microorganisms, predominantly within the gastrointestinal tract, collectively called the gut microbiota. Investigations have revealed the bidirectional communication between the gut microbiota and the brain, characterized as the "microbiota-gut-brain axis." This axis represents an important regulator of brain development and function, immune system development, and nutrient metabolism, making it a target for efforts to alleviate the development and progression of neurodegenerative diseases (NDDs). Despite extensive biomedical and clinical research, our understanding of the causes, optimal treatment, and progression of NDDs remains limited. This paper aims to summarize the available knowledge on the role played by gut microbiota and how it is connected to the progression of neurodegenerative conditions; in particular, the relationship between the microbiota and gut-brain communications and the gut microbiota and neuro-immune conditions is reviewed. We discuss how and why the gut immune system communicates with the brain and how this communication impacts neurodegeneration. Next, we examine the alterations in the gut microbiota, immune response, and brain changes associated with gut dysbiosis. Finally, we highlight the preclinical and clinical evidence for probiotics, prebiotics, fecal microbiota transplantation, dietary supplements, natural drugs, and exercise intervention as potential therapeutic approaches that could lead to a new treatment paradigm for NDDs.}, }
@article {pmid39653685, year = {2024}, author = {Li, X and Zheng, P and Zou, Y and Guan, L and Li, N and Liu, J and Lu, N and Zhu, Y and He, C}, title = {Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2436949}, pmid = {39653685}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Obesity/metabolism ; Mice ; *Inulin/pharmacology/administration &amp; dosage ; *Diet, High-Fat/adverse effects ; *Mice, Inbred C57BL ; Male ; *Pancreas/pathology/metabolism/drug effects ; *Pancreatitis/metabolism ; Dysbiosis/microbiology ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Bacteria/classification/isolation &amp; purification/metabolism/genetics ; }, abstract = {Obesity is a definitive factor of severity and mortality of acute pancreatitis (AP), and gut microbiota dysbiosis is involved in its pathogenesis. However, the effect of gut microbiota modulation by dietary components on high fat diet (HFD)-induced severe AP remains unclear. Here, we found that the inulin, a soluble dietary fiber, mitigated pancreatic injury and systematic inflammation in mice fed HFD, which was dependent on gut microbiota as this protective effect was attenuated in germ-free mice. Inulin treatment suppressed the overgrowth of pathogenic bacteria Escherichia Shigella, Enterococcus, Klebsiella, while increased the abundance of probiotics Akkermansia. Fecal microbiota transplantation from inulin-treated mice to recipient mice reduced pancreatic damage and remodeled intestinal homeostasis. Additionally, inulin increased fecal short chain fatty acids (SCFAs), strengthened gut barrier and restored Paneth cells. The beneficial effect of inulin on improving pancreatic damage and leaky gut was diminished after the suppression of SCFAs. Notably, SCFAs administration, especially butyrate, to HFD mice blocked pancreatic and intestinal injury with the inhibition of histone deacetylase 3 (HDAC3), and pharmacological HDAC3 inhibition mimicked the ameliorative effect of SCFAs. Mechanically, butyrate modulated macrophage M1/M2 polarization balance by suppressing HDAC3 and subsequent acetylation of histone H3K27. Collectively, our data offer new insights into the gut microbiota-pancreas axis that may be leveraged to augment the potential supplementation of prebiotic inulin in the management of obesity associated severe AP.}, }
@article {pmid39653155, year = {2025}, author = {Zhao, Y and Sun, S and Liu, J and Zheng, M and Liu, M and Liu, J and Liu, H}, title = {Investigation of the protective mechanism of paeoniflorin against hyperlipidemia by an integrated metabolomics and gut microbiota strategy.}, journal = {The Journal of nutritional biochemistry}, volume = {137}, number = {}, pages = {109831}, doi = {10.1016/j.jnutbio.2024.109831}, pmid = {39653155}, issn = {1873-4847}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Hyperlipidemias/drug therapy/prevention &amp; control/metabolism/microbiology ; *Glucosides/pharmacology ; *Monoterpenes/pharmacology ; Diet, High-Fat/adverse effects ; Male ; Metabolomics ; Mice, Inbred C57BL ; Mice ; Lipid Metabolism/drug effects ; Fecal Microbiota Transplantation ; *Hypolipidemic Agents/pharmacology ; }, abstract = {The prevalence of hyperlipidemia is gradually increasing globally, posing a serious threat to public health. Previous studies have shown that paeoniflorin (PF) effectively improved abnormal lipid metabolism in atherosclerotic mice. However, the anti-hyperlipidemia effect and potential mechanism of paeoniflorin remain unclear. The gut microbiota (GM) is closely related to hyperlipidemia. This study was aimed to investigate effects of PF on improving the health of high-fat diet (HFD)-induced hyperlipidemic mice by modulating GM. A hyperlipidemic mouse model was established using an HFD, and the hypolipidemic effect of PF was detected in vivo. Besides16S ribosomal RNA sequencing and SCFAs metabolic analysis were performed to explore the lipid-lowering mechanism of PF. Importantly, fecal microbiota transplantation (FMT) experiments were conducted to verify the lipid-lowering mechanism of PF. The results showed that PF significantly inhibited the development of hyperlipidemia, reduced serum lipid and inflammatory cytokine levels, and improved liver steatosis. In addition, 16S rRNA sequencing revealed that PF treatment significantly increased the relative abundance of Lactobacillus, Coprococcus, Blautia, Roseburia, and Bacteroides while reducing the relative abundance of Prevotella. Meanwhile, the results of targeted metabolomics indicate that PF therapy can effectively restore butyric acid and propionic acid levels in the intestine. The FMT experiments further demonstrated that PF improved hyperlipidemia by regulating GM and its metabolites. The above results provide a valuable theoretical basis for the development and application of PF as a functional food for hyperlipidemia.}, }
@article {pmid39652283, year = {2025}, author = {Lou, L and Zhou, L and Wang, Y}, title = {Gut Microbiota: A Modulator and Therapeutic Target for Chronic Pain.}, journal = {Molecular neurobiology}, volume = {62}, number = {5}, pages = {5875-5890}, pmid = {39652283}, issn = {1559-1182}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/drug effects ; *Chronic Pain/therapy/microbiology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Chronic pain is a prevalent condition, impacting nearly one-fifth of the global population. Despite the availability of various clinical treatments, each comes with inherent limitations, and few offer a complete cure, resulting in a significant social and economic burden. Therefore, it is important to determine the pathogenesis and causes of chronic pain. Numerous studies have shown a close link between the intestinal microflora and chronic pain. The gut microbiota can exert their effects on chronic pain through both central and peripheral mechanisms and is able to communicate with the brain through its own components or metabolites. They also can regulate chronic pain by affecting pro- and anti-inflammatory cells. This review is aimed at reviewing the connection between gut flora and different types of chronic pain, including visceral pain, neuropathic pain, inflammatory pain, musculoskeletal pain, migraine, and chronic cancer pain; exploring the central and peripheral mechanisms of the influence of gut flora on chronic pain; and attempting to provide novel treatment options for chronic pain, that is, the gut microbiota can be regulated by probiotics, fecal microbial transplantation, and natural products to treat chronic pain. By examining the intricate relationship between gut flora and chronic pain, the review sought to pave the way for new treatment strategies that target the gut microbiota, offering hope for more effective pain management.}, }
@article {pmid39651062, year = {2024}, author = {Kaundal, S and Patil, AN and Ks, L and Sharma, V and Arora, A and Singh, C and Jandial, A and Jain, A and Prakash, G and Khadwal, A and Malhotra, P and Lad, DP}, title = {A role for diet and gut microbiota metabolites in autologous hematopoietic cell transplant recipients.}, journal = {Blood cell therapy}, volume = {7}, number = {4}, pages = {101-105}, pmid = {39651062}, issn = {2432-7026}, abstract = {INTRODUCTION: The gut microbiome has an established role in allogeneic hematopoietic cell transplantation (allo-HCT), but not in an auto-HCT setting. We have hypothesized that fecal short-chain fatty acids (SCFA) and urinary 3-indoxyl sulfate (3-IS), which are metabolites derived from the action of the gut microbiome on dietary fiber, play a role in auto-HCT outcomes.<br><br>METHODS: This was a single-center prospective study involving auto-HCT recipients. Baseline patient and disease details, diet diaries, and antibiotic exposure were recorded in consenting patients. Serial (pre-HCT, week two, and week four post-HCT) SCFA and urine 3-IS levels were measured using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). HCT outcomes were correlated with these metabolites.<br><br>RESULTS: Thirty patients (myeloma, n=13; lymphoma, n=17) were analyzed. The levels of urinary 3-IS, fecal acetate, propionate, and butyrate were found to be decreased at week two and were recovered by week four post-HCT. Those with low median nadir fecal butyrate levels at week two also had significantly lower pre-HCT and week four butyrate levels. Recipients with low butyrate levels had more grade &#x2265;2 mucositis (80% vs. 33%, p=0.01) and low fiber intake (10.4 g vs. 13.6 g, p=0.04). They also had more carbapenem exposure (93% vs. 47%, p=0.005) and prolonged antibiotics (11 days vs. 8 days, p=0.008). There were no differences in the time to neutrophil or platelet engraftment, mortality, or disease response.<br><br>CONCLUSION: Low pre-HCT fecal butyrate levels tend to persist post-HCT and they are associated with mucositis, dietary fiber intake, and antibiotic exposure. The gut microbiome and its modulation may play a role in auto-HCT settings.}, }
@article {pmid39651029, year = {2024}, author = {Suresh, SB and Malireddi, A and Abera, M and Noor, K and Ansar, M and Boddeti, S and Nath, TS}, title = {Gut Microbiome and Its Role in Parkinson's Disease.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73150}, pmid = {39651029}, issn = {2168-8184}, abstract = {Parkinson's disease (PD) afflicted more than 8.5 million people globally in 2019, as the prevalence of the condition more than doubled during the preceding 25 years. Both non-motor symptoms, such as mood disorders and cognitive impairment, and motor symptoms, such as tremors and rigidity, are indicative of this progressive neurodegenerative disease. Recent data indicates a significant role for the gut microbiome in PD pathogenesis and progression, emphasizing the microbiota-gut-brain axis. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, this systematic review summarizes our current knowledge about the function of the gut microbiome in PD, highlighting recurrent microbial alterations and assessing microbiome-based treatment strategies. The review revealed several consistent patterns in the gut microbiota of PD patients, including reduced microbial diversity and specific taxonomic alterations, including a drop in Firmicutes abundance and an increase in Proteobacteria abundance. Functional changes in the gut microbiome, such as altered short-chain fatty acid (SCFA) production and tryptophan metabolism, were also noted. These microbial changes were observed even in early-stage and drug-naïve PD patients, suggesting they are not merely a consequence of disease progression or medication use. The review highlighted potential mechanisms linking gut microbiome alterations to PD, including increased intestinal permeability, neuroinflammation, and modulation of alpha-synuclein aggregation. Probiotics, prebiotics, and fecal microbiota transplantation are a few interventions that try to modify the gut microbiome and might be possible to halt the advancement of PD and enhance patients' quality of life with the condition. Future research should focus on establishing causality through large-scale longitudinal studies, standardizing microbiome analysis methods, and exploring personalized microbiome-based therapies.}, }
@article {pmid39650985, year = {2024}, author = {Ina, EA and Ziton, S and Dourvetakis, K and Corallo, JP}, title = {Loop Ileostomy With Colonic Lavage: Case Report of an Alternative to Total Colectomy in the Setting of Fulminant Clostridium difficile Colitis.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73141}, pmid = {39650985}, issn = {2168-8184}, abstract = {Fulminant Clostridium difficile colitis is a severe and potentially life-threatening form of Clostridium difficile-associated bacterial disease leading to inflammation and damage to the colon. Complications such as toxic megacolon, sepsis, and multi-organ failure commonly occur in individuals with compromised immune systems and recent antibiotic use. Management of Clostridium difficile colitis involves optimization of fluid and electrolyte balance, and elimination of bacteria commonly by administering vancomycin or fidaxomicin. In cases where pharmacological management has been ineffective, fecal microbiota transplantation and surgical intervention demonstrated success. Historically, surgical intervention has involved a total abdominal colectomy with end ileostomy; however, other surgical options have shown increasing benefits with preservation of the colon. This case report aims to provide an example of an alternative management strategy for fulminant Clostridium difficile infections, via the use of a loop ileostomy and colonic lavage. The combination of loop ileostomy and colonic lavage promotes bowel rest, removes toxins, and promotes healing while decreasing inflammation. As with all management modalities, it is essential to recognize the associated complications. The potential benefits should be carefully weighed against the risks on a case-by-case basis with the help of a multidisciplinary team as illustrated through this case report. Overall, early recognition and treatment of fulminant Clostridium difficile colitis using loop ileostomy and colonic lavage prevents further disease progression and improves patient outcomes.}, }
@article {pmid39649613, year = {2024}, author = {Moreau, GB and Young, M and Behm, B and Tanyüksel, M and Ramakrishnan, G and Petri, WA}, title = {FMT Restores Colonic Protein Biosynthesis and Cell Proliferation in Patients with Recurrent Clostridioides difficile Disease.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39649613}, support = {R01 AI124214/AI/NIAID NIH HHS/United States ; R01 AI152477/AI/NIAID NIH HHS/United States ; }, abstract = {Recurrent C. difficile infection (CDI) is a major health threat with significant mortality and financial costs. Fecal Microbiota Transplantation (FMT) is an effective therapy, however the mechanisms by which it acts, particularly on the host, are poorly understood. Here we enrolled a prospective cohort of human patients with recurrent CDI (n=16) undergoing FMT therapy. Colonic biopsies were collected and bulk RNA sequencing was performed to compare changes in host gene expression pre- and two months post-FMT. Transcriptional profiles were significantly altered after FMT therapy, with many differentially expressed genes (~15% of annotated genes detected). Enrichment analysis determined that these changes were reflective of increased protein production post-FMT, with enrichment of pathways such as Ribosome Biogenesis, Protein Processing, and signaling pathways (Myc, mTORc1, E2F) associated with cell proliferation and protein biosynthesis. Histology of H&amp;E-stained biopsies identified a significant increase in colonic crypt length post-FMT, suggesting that this treatment promotes cell proliferation. Crypt length was significantly correlated with enriched Myc and mTOR signaling pathways as well as genes associated with polyamine biosynthesis, providing a potential mechanism through which this may occur. Finally, signaling pathways upstream of Myc and mTOR, notably IL-33 Signaling and EGFR ligands, were significantly upregulated, suggesting that FMT may utilize these signals to promote cell proliferation and restoration of the intestine.}, }
@article {pmid39647752, year = {2025}, author = {Li, K and Ran, X and Han, J and Ding, H and Wang, X and Li, Y and Guo, W and Li, X and Guo, W and Fu, S and Bi, J}, title = {Astragalus polysaccharide alleviates mastitis disrupted by Staphylococcus aureus infection by regulating gut microbiota and SCFAs metabolism.}, journal = {International journal of biological macromolecules}, volume = {286}, number = {}, pages = {138422}, doi = {10.1016/j.ijbiomac.2024.138422}, pmid = {39647752}, issn = {1879-0003}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Polysaccharides/pharmacology/chemistry/therapeutic use ; Female ; *Staphylococcal Infections/microbiology/drug therapy/metabolism/complications ; *Astragalus Plant/chemistry ; Mice ; *Staphylococcus aureus/drug effects ; *Fatty Acids, Volatile/metabolism ; *Mastitis/microbiology/drug therapy/metabolism ; Mammary Glands, Animal/drug effects/microbiology ; Oxidative Stress/drug effects ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {Polysaccharides, key bioactive compounds derived from Chinese herbs, are increasingly recognized for their therapeutic potential in modulating gut microbiota to treat various diseases. However, their efficacy in alleviating mammary inflammation and oxidative stress and protecting the blood-milk barrier (BMB) compromised by Staphylococcus aureus (S. au) infection remains uncertain. As evidence for the gut-mammary axis grows, identifying natural prebiotic components that affect this axis is crucial. This study reveals that Astragalus polysaccharide (APS), the primary active constituent of Astragalus, effectively mitigates S. au infection in murine mammary glands, suppresses inflammatory responses, reduces oxidative stress, and restores BMB integrity. The involvement of APS in modulating gut microbiota was substantiated through gut microbial depletion experiments and fecal microbiota transplantation (FMT). Notably, APS uniquely enriched Ruminococcus bromii (R. bromii) in the gut, facilitating the metabolism of short-chain fatty acids (SCFAs), particularly acetate and butyrate, which are pivotal to APS's protective effects. Collectively, these results propose a novel therapeutic approach for the treatment and prevention of S. au-induced mastitis, leveraging APS and R. bromii as prebiotics and probiotics, respectively.}, }
@article {pmid39647571, year = {2025}, author = {Sharma, A and Kapur, S and Kancharla, P and Yang, T}, title = {Sex differences in gut microbiota, hypertension, and cardiovascular risk.}, journal = {European journal of pharmacology}, volume = {987}, number = {}, pages = {177183}, pmid = {39647571}, issn = {1879-0712}, support = {852969/AHA/American Heart Association-American Stroke Association/United States ; R21 AG079357/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Hypertension/microbiology ; *Cardiovascular Diseases/microbiology ; *Sex Characteristics ; Animals ; Female ; Fecal Microbiota Transplantation ; Male ; Sex Factors ; Probiotics/therapeutic use ; Heart Disease Risk Factors ; }, abstract = {The intricate ecosystem of the gut microbiome exhibits sex-specific differences, influencing the susceptibility to cardiovascular diseases (CVD). Imbalance within the gut microbiome compromises the gut barrier, activates inflammatory pathways, and alters the production of metabolites, all of which initiate chronic diseases including CVD. In particular, the interplay between lifestyle choices, hormonal changes, and metabolic byproducts uniquely affects sex-specific gut microbiomes, potentially shaping the risk profiles for hypertension and CVD differently in men and women. Understanding the gut microbiome's role in CVD risk offers informative reasoning behind the importance of developing tailored preventative strategies based on sex-specific differences in CVD risk. Furthermore, insight into the differential impact of social determinants and biological factors on CVD susceptibility emphasizes the necessity for more nuanced approaches. This review also outlines specific dietary interventions that may enhance gut microbiome health, offering a glimpse into potential therapeutic avenues for reducing CVD risk that require greater awareness. Imbalance in natural gut microbiomes may explain etiologies of chronic diseases; we advocate for future application to alter the gut microbiome as possible treatment of the aforementioned diseases. This review mentions the idea of altering the gut microbiome through interventions such as fecal microbiota transplantation (FMT), a major application of microbiome-based therapy that is first-line for Clostridium difficile infections and patient-specific probiotics highlights more innovative approaches to hypertension and CVD prevention. Through increased analysis of gut microbiota compositions along with patient-centric probiotics and microbiome transfers, this review advocates for future preventative strategies for hypertension.}, }
@article {pmid39647535, year = {2025}, author = {Casañas-Martínez, M and Barbero-Herranz, R and Alegre-González, D and Mosquera-Lozano, JD and Del Campo, R and , }, title = {Fecal microbiota transplantation in a long-standing auto-brewery syndrome with complex symptomatology.}, journal = {Journal of hepatology}, volume = {82}, number = {4}, pages = {e186-e188}, doi = {10.1016/j.jhep.2024.12.005}, pmid = {39647535}, issn = {1600-0641}, }
@article {pmid39645284, year = {2024}, author = {Dean, NJ and d'Arienzo, PD and Ibraheim, H and Lee, KA and Olsson-Brown, AC and Pinato, DJ and Powell, N}, title = {The role of the gut microbiome in regulating the response to immune checkpoint inhibitor therapy.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101944}, doi = {10.1016/j.bpg.2024.101944}, pmid = {39645284}, issn = {1532-1916}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Neoplasms/drug therapy/microbiology/immunology ; Immunotherapy/methods ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use/pharmacology ; }, abstract = {Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy, yet the proportion of patients who achieve long-term disease control remain suboptimal. Over the past decade, the gut microbiome has been shown to influence immune-mediated tumour suppression as well as responses to ICI therapies. Compositional differences in gut microbiome may account for the differences in outcomes from immune checkpoint blockade. Identifying microbiota species associated with favourable/unfavourable outcomes and modelling their dynamics throughout the course of ICI treatment could help develop predictive biomarkers of immunotherapy response, and manipulating the gut microbiome represent a novel approach to enhancing ICI effectiveness. Clinically, this raises the prospect of using gut microbiome-based therapies to overcome primary resistance to ICIs, mitigate the effects of microbiome-altering drugs such as antibiotics or proton pump inhibitors, and improve overall survival in patients across numerous different cancer types.}, }
@article {pmid39645282, year = {2024}, author = {Józefczuk, P and Biliński, J and Minkowska, A and Łaguna, P}, title = {Gut microbiome in children undergoing hematopoietic stem cell transplantation.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101955}, doi = {10.1016/j.bpg.2024.101955}, pmid = {39645282}, issn = {1532-1916}, mesh = {Animals ; Child ; Humans ; *Gastrointestinal Microbiome/physiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Adult ; }, abstract = {Hematopoietic stem cell transplantation (HSCT) is used in children as a treatment for various cancers, e.g. acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or other diseases, e.g. severe congenital immunodeficiency, metabolic disorders, hence the patient population is quite diverse. There is an increasing interest on the role of the microbiome in peri-transplant period. In this review, concepts of HSCT with the focus on the importance of microbiome composition, its changes during treatment and possible microbiota oriented interventions will be discussed. This paper analyzes data in pediatric population, but in view of interesting results and absence of analogous data for pediatric patients, it also looks at studies performed on adult population and pre-clinical trials on animals discussing possible translation to children.}, }
@article {pmid39645278, year = {2024}, author = {Garcia-Mateo, S and Rondinella, D and Ponziani, FR and Miele, L and Gasbarrini, A and Cammarota, G and Lanas, &#xc1; and Gomollón, F}, title = {Gut microbiome and metabolic dysfunction-associated steatotic liver disease: Pathogenic role and potential for therapeutics.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101924}, doi = {10.1016/j.bpg.2024.101924}, pmid = {39645278}, issn = {1532-1916}, mesh = {Humans ; Diet, Mediterranean ; Dysbiosis/metabolism/microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; *Non-alcoholic Fatty Liver Disease/metabolism/microbiology/therapy ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; }, abstract = {Gut microbiota plays key functions in the human body, and its alteration is associated with several human disorders. Moreover, its manipulation is being investigated as a potential therapeutic strategy. In this narrative review we will dissect the involvement of the gut microbiota and of the gut-liver axis on metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, we will review the effects of lifestyle interventions commonly used for MASLD (i.e. Mediterranean diet and physical exercise) on gut microbiome, to understand if their beneficial effect can be microbially mediated. Finally, we will discuss the role and the available evidence of therapeutic microbiome modulators, including prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT), in the management of MASLD.}, }
@article {pmid39643421, year = {2025}, author = {Zhang, S and Zhou, R and Xie, X and Xiong, S and Li, L and Li, Y}, title = {Polysaccharides from Lycium barbarum, yam, and sunflower ameliorate colitis in a structure and intrinsic flora-dependent manner.}, journal = {Carbohydrate polymers}, volume = {349}, number = {Pt A}, pages = {122905}, doi = {10.1016/j.carbpol.2024.122905}, pmid = {39643421}, issn = {1879-1344}, mesh = {Animals ; *Dioscorea/chemistry ; Mice ; *Mice, Inbred C57BL ; *Gastrointestinal Microbiome/drug effects ; *Colitis/drug therapy/chemically induced ; *Helianthus/chemistry ; Female ; *Polysaccharides/pharmacology/chemistry ; Lycium/chemistry ; Mice, Inbred ICR ; Disease Models, Animal ; Cytokines/metabolism ; Drugs, Chinese Herbal/pharmacology/chemistry ; }, abstract = {Polysaccharides have been suggested to ameliorate metabolic diseases. However, their differential colitis-mitigating effects in mouse models with different colony structures remain poorly understood. Therefore, this study investigated the effects of polysaccharides from Lycium barbarum (LBP), sunflower (SP), and yam (YP) on colitis in C57BL/6 J (B6) mice born via vaginal delivery (VD) and in both caesarean section (CS)- and VD-born Institute of Cancer Research (ICR) mice. LBP was mainly composed of glucose (30.2 %), galactose (27.5 %), and arabinose (26.9 %). The main components of SP and YP were galacturonic acid (75.8 %) and glucose (98.1 %), respectively. Interestingly, LBP effectively alleviated body weight loss, reduced inflammatory cytokine levels, and restored intestinal barrier function in all three mouse models. Moreover, LBP decreased the abundance of norank_f__norank_o__Clostridia_UCG-014, Coriobacteriaceae_UCG-002, and norank_f_Eubacterium_coprostanoligenes_group in B6 mice, and the abundance of these genera positively correlated with pro-inflammatory cytokine levels. LBP increased the abundance of Lactobacillus, which was positively correlated with the levels of the protective factor, IL-10, in CS-born ICR mice. Collectively, our study suggests the potential application of LBP in the treatment of ulcerative colitis. We also provide an alternative method for restoring intestinal homeostasis in CS-born offspring.}, }
@article {pmid39643403, year = {2025}, author = {Zhang, Y and Ji, W and Qin, H and Chen, Z and Zhou, Y and Zhou, Z and Wang, J and Wang, K}, title = {Astragalus polysaccharides alleviate DSS-induced ulcerative colitis in mice by restoring SCFA production and regulating Th17/Treg cell homeostasis in a microbiota-dependent manner.}, journal = {Carbohydrate polymers}, volume = {349}, number = {Pt A}, pages = {122829}, doi = {10.1016/j.carbpol.2024.122829}, pmid = {39643403}, issn = {1879-1344}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/chemically induced/immunology ; *Th17 Cells/drug effects/immunology ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Dextran Sulfate ; *Polysaccharides/pharmacology/chemistry ; *T-Lymphocytes, Regulatory/drug effects/immunology/metabolism ; *Mice, Inbred C57BL ; Homeostasis/drug effects ; Fatty Acids, Volatile/metabolism ; Male ; Astragalus Plant/chemistry ; Astragalus propinquus/chemistry ; Fecal Microbiota Transplantation ; }, abstract = {Natural polysaccharides from Astragalus membranaceus have been shown to relieve ulcerative colitis (UC). However, the mechanism and causal relationship between the gut microbiota and Astragalus polysaccharides (APS) treatment of UC are unclear. The results of the present study showed that APS ameliorated colonic injury and the disruption of the gut microbiota and restored intestinal immune homeostasis in mice with DSS-induced colitis. Meanwhile, we found that APS treatment was ineffective in antibiotic-treated colitis mice but was effective when FMT (Fecal microbiota transplantation) was performed on UC mice using APS-treated mice as donors. APS increased the proportion of relevant microbiota that produce SCFAs and both direct administration of APS and administration of APS-adjusted gut microbiota significantly promoted the production of SCFAs in colitis mice. We demonstrated that APS dually inhibited NF-κB activation via the TLR4 and HDAC3 pathways and improved the balance in Th17/Treg cells in UC mice. In conclusion, our study revealed that APS is a promising prebiotic agent for the maintenance of intestinal health and demonstrated that APS may ameliorate colitis in a gut microbiota-dependent manner.}, }
@article {pmid39640634, year = {2024}, author = {Nezhadi, J and Fadaee, M and Ahmadi, S and Kafil, HS}, title = {Microbiota transplantation.}, journal = {Heliyon}, volume = {10}, number = {20}, pages = {e39047}, pmid = {39640634}, issn = {2405-8440}, abstract = {Microbiota refers to a collection of living microorganisms, including bacteria, yeasts, and viruses, that coexist in various sites of the human body. Microbiota can perform multiple functions in the body, which have an essential effect on human health and homeostasis. For example, the microbiota can digest polysaccharides, produce vitamins, modulate the immune system, and protect the body against pathogens. Various factors can occasionally alter the microbiota population in the human body, a condition known as dysbiosis. Dysbiosis can disrupt the homeostasis of a person's body and cause disease. Recent years have witnessed efforts to restore the microbiota population of an individual's body to its original state and eradicate dysbiosis through microbiota transplantation. The noteworthy point is that different methods such as fecal microbiota transplantation, vaginal microbiota transplantation (VMT), skin microbiota transplantation (SMT), oral microbiota transplantation (OMT), washed microbiota transplantation (WMT), and sinonasal microbiota transplantation (SiMT) are used for microbiota transplantation (MT). According to the results of studies and the usefulness of MT in improving a person's health, the purpose of this study is to investigate different methods of MT to eliminate dysbiosis.}, }
@article {pmid39640340, year = {2024}, author = {Ma, BDY and Chan, TYH and Lo, BWY}, title = {Unveiling the hidden culprit: How the brain-gut axis fuels neuroinflammation in ischemic stroke.}, journal = {Surgical neurology international}, volume = {15}, number = {}, pages = {394}, pmid = {39640340}, issn = {2229-5097}, abstract = {BACKGROUND: The brain-gut axis represents a bidirectional communication network between the gut microbiome and the central nervous system that plays an important role in homeostasis. Compelling evidence now confirms that ischemic stroke disrupts this delicate balance by inducing gut dysbiosis.<br><br>METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and Google Scholar for articles published between January 2000 and January 2023 using relevant keywords. Studies were limited to English and included original studies, literature, and systematic reviewers from peer-reviewed journals which discussed gut microbiota composition in models/subjects with ischemic stroke or assessed stroke impact on gut microbiota. Comments, meeting abstracts, and case reports were excluded. From the 80 relevant articles, we summarized key findings related to gut microbiota changes after stroke and their association with stroke outcomes.<br><br>RESULTS: Emerging preclinical evidence underscores the pivotal role of the gut microbiome in glial cell development and function. Germ-free models exhibit compromised microglial activation and impaired cellular debris clearance, exacerbating tissue damage following ischemic stroke. Targeted interventions, including prebiotics, probiotics, and fecal microbiota transplantation, have demonstrated efficacy in rescuing glial phenotypes in preclinical stroke models. Beyond its local effects, the gut microbiome significantly influences systemic immunity. Ischemic stroke polarizes pro-inflammatory phenotypes of neutrophils and T cells, amplifying neurovascular inflammation. Microbiota manipulation modulates leukocyte trafficking and metabolic signaling, offering potential avenues to mitigate infarct pathology.<br><br>CONCLUSION: Our review demonstrates that in preclinical stroke models, modulating the lipopolysaccharide, short-chain fatty acid, and trimethylamine N-oxide pathways through the gut-brain axis reduces infarct sizes and edema and improves functional recovery after ischemic stroke. Further exploration of this important axis may unveil additional adjunctive stroke therapies by elucidating the complex interplay between the microbiome and the brain. Rigorously controlled clinical studies are now warranted to translate these promising preclinical findings and investigate whether manipulating the microbiome-brain relationship can help improve outcomes for stroke patients. Overall, continued research on the gut-brain axis holds exciting possibilities for developing novel treatment strategies that may enhance recovery after stroke.}, }
@article {pmid39640265, year = {2024}, author = {Wang, H and Deng, F and Luo, M and Wang, X}, title = {Case report: Fecal microbiota transplant for Clostridium difficile infection in a pregnant patient with acute severe ulcerative colitis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1417003}, pmid = {39640265}, issn = {1664-3224}, mesh = {Humans ; Female ; *Fecal Microbiota Transplantation ; Pregnancy ; *Colitis, Ulcerative/therapy/immunology/microbiology ; Adult ; *Clostridium Infections/therapy/immunology ; Clostridioides difficile ; Gastrointestinal Microbiome ; Pregnancy Complications, Infectious/therapy/microbiology ; Treatment Outcome ; Acute Disease ; Severity of Illness Index ; }, abstract = {Ulcerative colitis (UC) is a chronic colonic mucosal inflammation characterized by reduced gut microbial diversity. Patients with UC at pregnancy are prone to suffer from severe disease progression due to the changes of hormone and immune regulation. Fecal microbiota transplant (FMT) is a promising therapy for UC and recurrent Clostridium difficile infection (CDI). However, acute severe ulcerative colitis (ASUC) treatment especially in patients at pregnancy is clinically challenging. Herein, we report a 34-year-old pregnant woman who manifested with numerous bloody stools and markedly elevated serological inflammatory indicators and was diagnosed with ASUC and concurrent CDI. The use of intravenous injection steroids and anti-TNF-α therapy failed to improve her condition. Frozen encapsulated FMT therapy was finally performed to this patient with clearly improved symptoms and indications of safe delivery without UC flares or complications, and markedly increased diversity of the gut microbiota was also shown in this patient after FMT. This report firstly describes FMT as a safe salvage therapy for a pregnant patient with CDI and ASUC refractory to intravenous steroids and anti-TNF therapy.}, }
@article {pmid39638178, year = {2025}, author = {Gong, JZ and Huang, JJ and Pan, M and Jin, QW and Fan, YM and Shi, WQ and Huang, SY}, title = {Cathepsin L of Fasciola hepatica meliorates colitis by altering the gut microbiome and inflammatory macrophages.}, journal = {International journal of biological macromolecules}, volume = {286}, number = {}, pages = {138270}, doi = {10.1016/j.ijbiomac.2024.138270}, pmid = {39638178}, issn = {1879-0003}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Fasciola hepatica/enzymology ; Mice ; *Macrophages/drug effects/immunology/metabolism ; *Cathepsin L/pharmacology/metabolism ; Dextran Sulfate ; *Colitis, Ulcerative/chemically induced/microbiology/pathology ; *Colitis/microbiology/chemically induced/pathology ; NF-kappa B/metabolism ; Male ; Disease Models, Animal ; Fecal Microbiota Transplantation ; RAW 264.7 Cells ; *Helminth Proteins/pharmacology ; }, abstract = {Helminths can relieve the development of autoimmune diseases and inflammatory diseases, by inducing anti-inflammatory innate immune responses. Here, we report that CL7, a Cathepsin L protein secreted by Fasciola hepatica, inhibited the activation of the NF-κB and MAPK signaling resulting in reduced secretion of inflammatory mediators in macrophages. Furthermore，we found that CL7 could prevent dextran sulfate sodium (DSS) induced ulcerative colitis (UC). CL7 and ESP administration restored DSS-induced body weight loss, colon shortening, and injury, significantly decreased the disease activity index (DAI) and alleviated colonic epithelial injury. CL7 noticeably suppressed the DSS-triggered M1 polarization upregulation and inhibited IL-17 and other inflammatory mediator production in UC mice. Additionally, CL7 ameliorated DSS-induced microbiota dysbiosis. Results of Antibiotic treatment (ABX) and fecal microbial transplants (FMT) suggested that the gut microbiota played an important role in CL7 treating UC. These findings propose that CL7 could be a promising strategy for UC therapy.}, }
@article {pmid39635024, year = {2024}, author = {Skladany, L and Kubanek, N and Adamcova Selcanova, S and Zilincanova, D and Havaj, D and Sulejova, K and Soltys, K and Messingerova, L and Lichvar, M and Laffers, L and Zilincan, M and Honsova, E and Liptak, P and Banovcin, P and Bures, J and Koller, T and Golubnitschaja, O and Arab, JP}, title = {3PM-guided innovation in treatments of severe alcohol-associated hepatitis utilizing fecal microbiota transplantation.}, journal = {The EPMA journal}, volume = {15}, number = {4}, pages = {677-692}, pmid = {39635024}, issn = {1878-5077}, abstract = {RATIONALE: Severe alcohol-associated hepatitis (SAH) is the most critical, acute, inflammatory phenotype within the alcohol-associated liver disease (ALD) spectrum, characterized by high 30- and 90-day mortality. Since several decades, corticosteroids (CS) are the only approved pharmacotherapy offering highly limited survival benefits. Contextually, there is an evident demand for 3PM innovation in the area meeting patients' needs and improving individual outcomes. Fecal microbiota transplantation (FMT) has emerged as one of the new potential therapeutic options. In this study, we aimed to address the crucial 3PM domains in order to assess (i) the impact of FMT on mortality in SAH patients beyond CS, (ii) to identify factors associated with the outcome to be improved (iii) the prediction of futility, (iv) prevention of suboptimal individual outcomes linked to increased mortality, and (v) personalized allocation of therapy.<br><br>METHODS: We conducted a prospective study (NCT04758806) in adult patients with SAH who were non-responders (NR) to or non-eligible (NE) for CS between January 2018 and August 2022. The intervention consisted of five 100&#xa0;ml of FMT, prepared from 30&#xa0;g stool from an unrelated healthy donor and frozen at&#x2009;-&#x2009;80 &#xb0;C, administered daily to the upper gastrointestinal (GI) tract. We evaluated the impact of FMT on 30- and 90-day mortality which we compared to the control group selected by the propensity score matching and treated by the standard of care; the control group was derived from the RH7 registry of patients hospitalized at the liver unit (NCT04767945). We have also scrutinized the FMT outcome against established and potential&#xa0;prognostic factors for SAH - such as the model for end-stage liver disease (MELD), Maddrey Discriminant Function (MDF), acute-on-chronic liver failure (ACLF), Liver Frailty Index (LFI), hepatic venous-portal pressure gradient (HVPG) and Alcoholic Hepatitis Histologic Score (AHHS) - to see if the 3PM method assigns them a new dimension in predicting response to therapy, prevention of suboptimal individual outcomes, and personalized patient management.<br><br>RESULTS: We enrolled 44 patients with SAH (NR or NE) on an intention-to-treat basis; we analyzed 33 patients per protocol for associated factors (after an additional 11 being excluded for receiving less than 5 doses of FMT), and 31 patients by propensity score matching for corresponding individual outcomes, respectively. The mean age was 49.6&#xa0;years, 11 patients (33.3%) were females. The median MELD score was 29, and ACLF of any degree had 27 patients (81.8%). FMT improved 30-day mortality (p&#x2009;=&#x2009;0.0204) and non-significantly improved 90-day mortality (p&#x2009;=&#x2009;0.4386). Univariate analysis identified MELD&#x2009;&#x2265;&#x2009;30, MDF&#x2009;&#x2265;&#x2009;90, and ACLF grade&#x2009;>&#x2009;1 as significant predictors of 30-day mortality, (p&#x2009;=&#x2009;0.031; p&#x2009;=&#x2009;0.014; p&#x2009;=&#x2009;0.034). Survival was not associated with baseline LFI, HVPG, or AHHS.<br><br>In the most difficult-to-treat sub-cohort of patients with SAH (i.e., NR/NE), FMT improved 30-day mortality. Factors associated with benefit included MELD&#x2009;&#x2264;&#x2009;30, MDF&#x2009;&#x2264;&#x2009;90, and ACLF&#x2009;<&#x2009;2. These results support the potential of gut microbiome as a therapeutic target in the context of 3PM research and vice versa - to use 3PM methodology as the expedient unifying template for microbiome research. The results allow for immediate impact on the innovative concepts of (i) personalized phenotyping and stratification of the disease for the clinical research and practice, (ii) multilevel predictive diagnosis related to personalized/precise treatment allocation including evidence-based (ii) prevention of futile and sub-optimally effective therapy, as well as (iii) targeted prevention of poor individual outcomes in patients with SAH. Moreover, our results add to the existing evidence with the potential to generate new research along the SAH's pathogenetic pathways such as diverse individual susceptibility to alcohol toxicity, host-specific mitochondrial function and systemic inflammation, and the role of gut dysbiosis thereof.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-024-00381-5.}, }
@article {pmid39633321, year = {2024}, author = {Farias, RM and Jiang, Y and Levy, EJ and Hwang, C and Wang, J and Burton, EM and Cohen, L and Ajami, N and Wargo, JA and Daniel, CR and McQuade, JL}, title = {Diet and Immune Effects Trial (DIET)- a randomized, double-blinded dietary intervention study in patients with melanoma receiving immunotherapy.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {1493}, pmid = {39633321}, issn = {1471-2407}, support = {R25 CA203650/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Diet ; Dietary Fiber/administration &amp; dosage ; Double-Blind Method ; *Gastrointestinal Microbiome/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy/methods ; *Melanoma/therapy/immunology/diet therapy ; Quality of Life ; Skin Neoplasms/diet therapy/immunology/therapy ; Clinical Trials, Phase II as Topic ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Gut microbiome modulation is a promising strategy for enhancing the response to immune checkpoint blockade (ICB). Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB-naïve and refractory melanoma patients; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota, and we have previously shown that (a) habitual high dietary fiber intake is associated with an improved response to ICB and (b) fiber manipulation in mice impacts antitumor immunity. We recently demonstrated the feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and tolerance. Building on this, we are now conducting a phase II randomized trial of HFDI versus a healthy control diet in melanoma patients receiving ICB.<br><br>METHODS: This is a randomized, double-blind, fully controlled feeding study that will enroll 45 melanoma patients starting standard-of-care (SOC) ICB in three settings: adjuvant, neoadjuvant, and unresectable. Patients are randomized 2:1 to the HFDI (target fiber 50&#xa0;g/day from whole foods) or healthy control diet (target fiber 20&#xa0;g/day) stratified by BMI and cohort. All meals are prepared by the MD Anderson Bionutrition Core and are isocaloric and macronutrient-controlled. The intervention includes a 1-week equilibration period and then up to 11 weeks of diet intervention. Longitudinal blood, stool and tumor tissue (if available) are collected throughout the trial and at 12 weeks post intervention.<br><br>DISCUSSION: This DIET study is the first fully controlled feeding study among cancer patients who are actively receiving immunotherapy. The goal of the current study is to establish the effects of dietary intervention on the structure and function of the gut microbiome in patients with melanoma treated with SOC immunotherapies. The secondary endpoints include changes in systemic and tumor immunity, changes in the metabolic profile, quality of life, symptoms, disease response and immunotherapy toxicity.<br><br>TRIAL REGISTRATION: This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT04645680. First posted 2020-11-27; last verified 2024-06.}, }
@article {pmid39633000, year = {2025}, author = {Yang, D and Fu, S and Shi, Y}, title = {Gut microbiota modulation: a novel mechanism in arb-mediated hypertension treatment.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {48}, number = {3}, pages = {1211-1213}, pmid = {39633000}, issn = {1348-4214}, }
@article {pmid39631325, year = {2024}, author = {Zhang, Y and Liu, Q and Xie, H and Zhang, W and Lin, X and Zhang, H and Yu, H and Ma, Y and Zhang, C and Geng, H and Shi, N and Cui, L and Li, B and Li, YF}, title = {Fecal microbiota transplantation as an effective way in treating methylmercury-poisoned rats.}, journal = {The Science of the total environment}, volume = {957}, number = {}, pages = {177850}, doi = {10.1016/j.scitotenv.2024.177850}, pmid = {39631325}, issn = {1879-1026}, mesh = {Animals ; *Methylmercury Compounds/metabolism ; *Fecal Microbiota Transplantation ; Rats ; *Gastrointestinal Microbiome ; Male ; Feces/microbiology ; }, abstract = {Methylmercury (MeHg) can cause devastating neurotoxicity in animals and human beings. Gut microbiota dysbiosis has been found in MeHg-poisoned animals. Fecal microbiota transplantation (FMT) has been shown to improve clinical outcomes in a variety of diseases such as epilepsy, amyotrophic lateral sclerosis (ALS) and autism. The aim of this study was to investigate the effects of FMT on MeHg-poisoned rats. FMT treatment was applied to MeHg-poisoned rats for 14 days. The neurobehavior, weight changes, dopamine (DA), the total Hg and MeHg level were evaluated. Besides, the gut microbiota and metabolites change in feces were also checked. It was found that FMT helped weight gain, alleviated the neurological disorders, enhanced fecal mercury excretion and MeHg demethylation, reconstructed gut microbiome and promoted the production of gut-brain axis related-metabolites in MeHg-poisoned rats. This study elaborates on the therapeutic efficacy of FMT in treating of MeHg-poisoned rats, which sheds lights on the treatment of neurological diseases like Minamata Disease and even Parkinson's Disease.}, }
@article {pmid39630000, year = {2025}, author = {Barbosa, IG and Miranda, AS and Berk, M and Teixeira, AL}, title = {The involvement of the microbiota-gut-brain axis in the pathophysiology of mood disorders and therapeutic implications.}, journal = {Expert review of neurotherapeutics}, volume = {25}, number = {1}, pages = {85-99}, doi = {10.1080/14737175.2024.2438646}, pmid = {39630000}, issn = {1744-8360}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Brain-Gut Axis/physiology ; *Mood Disorders/therapy/physiopathology ; *Fecal Microbiota Transplantation ; Bipolar Disorder/therapy/physiopathology/microbiology ; Prebiotics/administration &amp; dosage ; }, abstract = {INTRODUCTION: There is a growing body of evidence implicating gut-brain axis dysfunction in the pathophysiology of mood disorders. Accordingly, gut microbiota has become a promising target for the development of biomarkers and novel therapeutics for bipolar and depressive disorders.<br><br>AREAS COVERED: We describe the observed changes in the gut microbiota of patients with mood disorders and discuss the available studies assessing microbiota-based strategies for their treatment.<br><br>EXPERT OPINION: Microbiota-targeted interventions, such as symbiotics, prebiotics, paraprobiotics, and fecal microbiota transplants seem to attenuate the severity of depressive symptoms. The available results must be seen as preliminary and need to be replicated and/or confirmed in larger and independent studies, also considering the pathophysiological and clinical heterogeneity of mood disorders.}, }
@article {pmid39629909, year = {2025}, author = {Sin, HCL and Haifer, C}, title = {Faecal transplantation: the good, the bad and the ugly.}, journal = {Internal medicine journal}, volume = {55}, number = {1}, pages = {35-40}, doi = {10.1111/imj.16559}, pmid = {39629909}, issn = {1445-5994}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects/trends ; *Gastrointestinal Microbiome/physiology ; *Feces/microbiology ; }, abstract = {There continues to be significant interest from both clinicians and patients in using faecal transplantation, as the integral role of the gut microbiome is increasingly recognised in various disease conditions, both within and beyond the gut. This Clinical Perspectives article provides an overview of existing literature, factors limiting the use of faecal microbial transplantation in clinical practice and exciting new advancements on the horizon.}, }
@article {pmid39628464, year = {2024}, author = {Hu, X and Wu, Q and Huang, L and Xu, J and He, X and Wu, L}, title = {Clinical efficacy of washed microbiota transplantation on metabolic syndrome and metabolic profile of donor outer membrane vesicles.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1465499}, pmid = {39628464}, issn = {2296-861X}, abstract = {OBJECT: To clarify the clinical efficacy of washed microbiota transplantation (WMT) for metabolic syndrome (MetS), and explore the differences in the metabolic profile of bacterial outer membrane vesicles (OMVs) in donor fecal bacteria suspension received by MetS patients with good and poor outcomes, and to construct a predictive model for the efficacy of WMT for MetS using differential metabolites.<br><br>METHODS: Medical data 65 MetS patients who had completed at least 2 courses of WMT from 2017.05 to 2023.07 were collected. Fecal bacteria suspension of WMT donors were collected, and the clinical data of MetS patients treated with WMT during this period were collected as well. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared. OMVs were isolated from donor fecal bacteria suspension and off-target metabolomic sequencing was performed by Liquid Chromatograph Mass Spectrometer (LC-MS).<br><br>RESULTS: Compared with baseline, Body mass index (BMI), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) of MetS patients showed significant decreases after the 1st (short-term) and 2nd (medium-term) courses, and fasting blood glucose (FBG) also showed significant decreases after the 1st session. There was a significant difference between the Marked Response OMVs and the Moderate Response OMVs. It was showed that 960 metabolites were significantly up-regulated in Marked Response OMVs and 439 metabolites that were significantly down-regulated. The ROC model suggested that 9-carboxymethoxymethylguanine, AUC&#x2009;=&#x2009;0.8127, 95% CI [0.6885, 0.9369], was the most potent metabolite predicting the most available metabolite for efficacy.<br><br>CONCLUSION: WMT had significant short-term and medium-term clinical efficacy in MetS. There were differences in the structure of metabolites between Marked Response OMVs and Moderate Response OMVs. The level of 9-Carboxy methoxy methylguanine in Marked Response OMVs can be a good predictor of the efficacy of WMT in the treatment of MetS.}, }
@article {pmid39624719, year = {2024}, author = {Xiang, A and Chang, Y and Shi, L and Zhou, X}, title = {Mapping the relationship between alcohol use disorder and gut microbiota: a 20-year bibliometric study.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1457969}, pmid = {39624719}, issn = {1664-302X}, abstract = {BACKGROUND: Alcohol use disorder (AUD) is a psychiatric disorder that is widespread worldwide. Alcohol use is a significant contributor to the global burden of death, disability and disease. Modulation of the gut microbiota is a promising approach to improve the efficacy and minimize the adverse effects of colorectal cancer treatment. The relationship between the presence of microbes and AUD has been widely validated. However, few studies have examined this relationship using bibliometric methods. Therefore, this study analyzes the research hotspots and trends in human gut microbiology and AUD over the last two decades from a bibliometric perspective. This study aims at provide new directions for basic and clinical research in this field.<br><br>OBJECTIVE: A comprehensive discussion of the relationship between the current state of research and trends in AUD and intestinal flora.<br><br>METHODS: We collected publications from the Web of Science Core Collection database from 2003 to 2023 according to established inclusion criteria. We analyzed countries, institutions, authors, and research contributions using CiteSpace, VOSviewer, and Scimago Graphics to visualize research trends in the field.<br><br>RESULTS: A total of 2,102 publications were obtained, with a rapid increase in the number of publications since 2016. The United States and China are major contributors to the field and have established a network of partners in several countries. Five hundred ninety-five academic journals published articles on the topic. The author with the highest number of publications is Prof. Bernd Schnabl of the Department of Gastroenterology at the University of California, San Diego. In addition to "gut flora" and "AUD," high frequency words in the keyword co-occurrence network analysis included alcoholic liver disease, tryptophan metabolism, enterohepatic axis, and fecal microbial transplantation.<br><br>CONCLUSION: The results of this study provide a bibliometric analysis and visualization of key research areas in the gut microbiota and AUD over the past 20&#x2009;years. The results suggest that the role of the gut microbiota in AUD and its potential mechanisms, especially therapeutic targets, should be closely monitored and could become a hot topic in the field.}, }
@article {pmid39621384, year = {2024}, author = {Hoeg, A and Kuchma, N and Krane, A and Graiziger, C and Thomas, J and Kelly, CR and Khoruts, A}, title = {Oral Capsule FMT Combined With Bezlotoxumab Is a Successful Rescue Protocol Following Failure of FMT Alone in the Treatment of Recurrent C. difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000002108}, pmid = {39621384}, issn = {1539-2031}, abstract = {GOALS: Evaluate the benefit of adding bezlotoxumab to repeat fecal microbiota transplantation (FMT) in patients with recurrent Clostridioides difficile infections after the failure of FMT alone.<br><br>BACKGROUND: The initial failure of FMT in breaking the cycle of recurrent Clostridium difficile(C. difficile) infections is associated with a greater risk of subsequent failure. Our previous analysis showed that FMT failure is associated with delayed repair of fecal microbiota at 1 week after administration. We hypothesized that increasing the symptom-free interval by adding bezlotoxumab would improve the outcomes of a second FMT.<br><br>STUDY: A new rescue protocol that combines FMT with bezlotoxumab for patients who previously failed FMT alone was implemented in 2 academic medical centers. The clinical outcomes of a new protocol were captured in a prospective registry. The results were compared in a retrospective analysis of clinical outcomes of prior experience with repeat FMT by itself. All FMT preparations were standardized for dose. Bezlotoxumab administration was synchronized temporally with the second FMT to maximize its duration of action.<br><br>RESULTS: Our historical cure rate of second FMT in treatment of recurrent C. difficile infection was 48% (15/31 patients). Addition of bezlotoxumab to the second FMT resulted in a cure rate of 89% (24/27 patients).<br><br>CONCLUSIONS: Addition of bezlotoxumab markedly improved the cure rate of the second FMT following initial FMT failure. The rationale for the protocol design highlights the importance of understanding the pharmacokinetics of both bezlotoxumab and FMT. Similar principles may apply to other live biotherapeutic products that are becoming available for prevention of C. difficile infection recurrence.}, }
@article {pmid39619696, year = {2024}, author = {Kang, P and Bae, GS and Jeon, E and Choi, J and Hwang, EH and Kim, G and Baek, SH and Shim, K and An, YJ and Lim, KS and Kim, Y and Oh, T and Hong, JJ and Lee, WK and Kim, SH and Koo, BS}, title = {Comprehensive effects of fecal microbiota transplantation on cynomolgus macaques across various fecal conditions.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1458923}, pmid = {39619696}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) and probiotics therapies represent key clinical options, yet their complex effects on the host are not fully understood. We evaluated the comprehensive effects of FMT using diarrheal or normal feces, as well as probiotic therapies, on multiple anatomical sites in healthy cynomolgus macaques through colonoscopy and surgery. Our research revealed that FMT led to a partial microbiome transplantation without exhibiting the donor's fecal clinical characteristics. Notably, FMT increased insulin and C-peptide levels in each animal according time series, regardless of fecal conditions. Immunologically, a reduction in neutrophil-to-lymphocyte ratio were exclusively observed in femoral veins of FMT group. In blood chemistry analyses, reductions in aspartate aminotransferase, blood urea nitrogen, and creatinine were observed in the femoral veins, while elevated levels of alanine aminotransferase and calcium were exclusively detected in the portal veins. These changes were not observed in the probiotic group. Also, short chain fatty acids were significantly higher increase in portal veins rather than femoral veins. Transcriptome analysis of liver tissues showed that metabolic pathways were primarily affected by both FMT and probiotics therapies. In summary, FMT therapy significantly influenced metabolic, immunologic and transcriptomic responses in normal macaque models, regardless of fecal conditions. Also, these macaque models, which utilize surgery and colonoscopy, serve as a human-like preclinical platform for evaluating long-term effects and anatomically specific responses to gut-targeted interventions, without the need for animal sacrifice.}, }
@article {pmid39619695, year = {2024}, author = {Han, X and Zhang, BW and Zeng, W and Ma, ML and Wang, KX and Yuan, BJ and Xu, DQ and Geng, JX and Fan, CY and Gao, ZK and Arshad, M and Gao, S and Zhao, L and Liu, SL and Mu, XQ}, title = {Suppressed oncogenic molecules involved in the treatment of colorectal cancer by fecal microbiota transplantation.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1451303}, pmid = {39619695}, issn = {1664-302X}, abstract = {Dysbiosis of the intestinal microbiota is prevalent among patients with colorectal cancer (CRC). This study aims to explore the anticancer roles of the fecal microbiota in inhibiting the progression of colorectal cancer and possible mechanisms. The intestinal microbial dysbiosis in CRC mice was significantly ameliorated by fecal microbiota transplantation (FMT), as indicated by the restored ACE index and Shannon index. The diameter and number of cancerous foci were significantly decreased in CRC mice treated with FMT, along with the restoration of the intestinal mucosal structure and the lessening of the gland arrangement disorder. Key factors in oxidative stress (TXN1, TXNRD1, and HIF-1α); cell cycle regulators (IGF-1, BIRC5, CDK8, HDAC2, EGFR, and CTSL); and a critical transcription factor of the innate immune signal pathway (IRF5) were among the repressed oncogenic targets engaged in the FMT treatment of CRC. Correlation analysis revealed that their expressions were positively correlated with uncultured_bacterium_o_Mollicutes_RF39, Rikenellaceae_RC9_gut_group, and negatively correlated with Bacillus, Marvinbryantia, Roseburia, Angelakisella, Enterorhabdus, Bacteroides, Muribaculum, and genera of uncultured_bacterium_f_Eggerthellaceae, uncultured_bacterium_f_Xanthobacteraceae, Prevotellaceae_UCG-001, uncultured_bacterium_f_Erysipelotrichaceae, uncul-tured_bacterium_f_Lachnospiraceae, uncultured_bacterium_f_Ruminococcaceae, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-005, and uncultured_bacterium_f_Peptococcaceae. This study provides more evidence for the application of FMT in the clinical treatment of CRC.}, }
@article {pmid39619660, year = {2024}, author = {Xi, M and Ruan, Q and Zhong, S and Li, J and Qi, W and Xie, C and Wang, X and Abuduxiku, N and Ni, J}, title = {Periodontal bacteria influence systemic diseases through the gut microbiota.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1478362}, pmid = {39619660}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Diabetes Mellitus/microbiology ; Alzheimer Disease/microbiology ; Bacteria/classification/genetics/pathogenicity ; Cardiovascular Diseases/microbiology ; Mouth/microbiology ; Animals ; }, abstract = {Many systemic diseases, including Alzheimer disease (AD), diabetes mellitus (DM) and cardiovascular disease, are associated with microbiota dysbiosis. The oral and intestinal microbiota are directly connected anatomically, and communicate with each other through the oral-gut microbiome axis to establish and maintain host microbial homeostasis. In addition to directly, periodontal bacteria may also be indirectly involved in the regulation of systemic health and disease through the disturbed gut. This paper provides evidence for the role of periodontal bacteria in systemic diseases via the oral-gut axis and the far-reaching implications of maintaining periodontal health in reducing the risk of many intestinal and parenteral diseases. This may provide insight into the underlying pathogenesis of many systemic diseases and the search for new preventive and therapeutic strategies.}, }
@article {pmid39617896, year = {2024}, author = {Feng, R and Zhu, Q and Wang, A and Wang, H and Wang, J and Chen, P and Zhang, R and Liang, D and Teng, J and Ma, M and Ding, X and Wang, X}, title = {Effect of fecal microbiota transplantation on patients with sporadic amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled trial.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {566}, pmid = {39617896}, issn = {1741-7015}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Fecal Microbiota Transplantation/methods ; Double-Blind Method ; Female ; Male ; Middle Aged ; Aged ; Gastrointestinal Microbiome/physiology ; Treatment Outcome ; Quality of Life ; Adult ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder marked by the progressive loss of motor neurons. Recent insights into ALS pathogenesis underscore the pivotal role of the gut microbiome, prompting an investigation into the potential therapeutic impact of fecal microbiota transplantation (FMT) on sporadic ALS patients.<br><br>METHODS: Conducted as a double-blind, placebo-controlled, parallel-group, randomized clinical trial, the study enrolled 27 participants from October 2022 to April 2023. The participants were followed up for 6&#xa0;months from February 2023 to October 2023, during in-person visits at baseline, week 15, week 23, and week 35. The participants, evenly randomized, received either healthy donor FMT (FMT, n&#x2009;=&#x2009;14) or a mixture of 0.9% saline and food coloring (E150c) as sham transplantation (placebo, n&#x2009;=&#x2009;13). The primary outcome measured the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score from baseline to week 35. Secondary outcomes included changes in gastrointestinal and respiratory functions, muscle strength, autonomic function, cognition, quality of life, intestinal microbiome composition, and plasm neurofilament light chain protein (NFL). Efficacy and safety outcomes were assessed in the intention-to-treat population.<br><br>RESULTS: A total of 27 randomized patients (47% women; mean age, 67.2&#xa0;years), 24 participants completed the entire study. Notably, ALSFRS-R score changes exhibited no significant differences between FMT (6.1 [SD, 3.11]) and placebo (6.41[SD, 2.73]) groups from baseline to week 35. Secondary efficacy outcomes, encompassing respiratory function, muscle strength, autonomic function, cognition, quality of life, and plasm NFL, showed no significant differences. Nevertheless, the FMT group exhibited improvements in constipation, depression, and anxiety symptoms. FMT induced a shift in gut&#xa0;microbiome community composition, marked by increased abundance of Bifidobacterium, which persisted until week 15 (95% CI, 0.04 to 0.28; p&#x2009;=&#x2009;0.01). Gastrointestinal adverse events were the primary manifestations of FMT-related side effects.<br><br>CONCLUSIONS: In this clinical trial involving 27 sporadic ALS patients, FMT did not&#xa0;significantly slow the decline in ALSFRS-R score. Larger multicenter trials&#xa0;are needed to confirm the efficacy of FMT in sporadic ALS patients and to explore the underlying biological mechanisms.<br><br>TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR 2200064504.}, }
@article {pmid39617011, year = {2025}, author = {Berzack, S and Galor, A}, title = {Microbiome-based therapeutics for ocular diseases.}, journal = {Clinical &amp; experimental optometry}, volume = {108}, number = {2}, pages = {115-122}, pmid = {39617011}, issn = {1444-0938}, support = {U01 EY034686/EY/NEI NIH HHS/United States ; P30 EY014801/EY/NEI NIH HHS/United States ; I01 BX004893/BX/BLRD VA/United States ; I01 CX002633/CX/CSRD VA/United States ; I01 CX002015/CX/CSRD VA/United States ; U24 EY035102/EY/NEI NIH HHS/United States ; I21 RX003883/RX/RRD VA/United States ; R33 EY032468/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Eye Diseases/therapy/microbiology ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Anti-Bacterial Agents/therapeutic use ; Dysbiosis ; Prebiotics ; }, abstract = {The relationship between the gut microbiome and ocular health has garnered increasing attention within the scientific community. Recent research has focused on the gut-eye axis, examining whether imbalances within the gut microbiome can influence the development, progression and severity of ocular diseases, including dry eye disease, uveitis, and glaucoma. Dysbiosis within the gut microbiome is linked to immune dysregulation, chronic inflammation, and epithelial barrier dysfunction, all of which contribute to ocular pathology. This review synthesises current evidence on these associations, exploring how gut microbiome alterations drive disease mechanisms. Furthermore, it examines the therapeutic potential of microbiome-targeted interventions, including antibiotics, prebiotics, probiotics, and faecal microbiota transplantation, all of which aim to restore microbial balance and modulate immune responses. As the prevalence of these conditions continues to rise, a deeper understanding of the gut-eye axis may facilitate the development of novel, targeted therapies to address unmet needs in the management of ocular diseases.}, }
@article {pmid39614243, year = {2024}, author = {Gan, G and Zhang, R and Zeng, Y and Lu, B and Luo, Y and Chen, S and Lei, H and Cai, Z and Huang, X}, title = {Fecal microbiota transplantation validates the importance of gut microbiota in an ApoE[-/-] mouse model of chronic apical periodontitis-induced atherosclerosis.}, journal = {BMC oral health}, volume = {24}, number = {1}, pages = {1455}, pmid = {39614243}, issn = {1472-6831}, support = {2022QNA073//Fujian Provincial Health Technology Project/ ; 2022GGA042//Fujian Provincial Health Technology Project/ ; 2023J01709//Fujian Province Natural Science Founding of China/ ; 81970926//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Atherosclerosis/microbiology/etiology ; *Gastrointestinal Microbiome ; Mice ; *Fecal Microbiota Transplantation ; *Periapical Periodontitis/microbiology/metabolism ; *Disease Models, Animal ; *Methylamines/blood/metabolism ; Apolipoproteins E ; Male ; Mice, Inbred C57BL ; Oxygenases/metabolism ; }, abstract = {BACKGROUND: Chronic apical periodontitis (CAP) has been linked to the development of atherosclerosis, although the underlying mechanisms remain unclear. This study aimed to investigate the role of gut microbiota disruption in CAP-induced atherosclerosis development, focusing on trimethylamine N-oxide (TMAO)-related metabolites.<br><br>METHODS: The study utilized fecal microbiota transplantation (FMT) to transfer gut microbiota from mice with CAP to healthy mice. Atherosclerosis development was assessed by analyzing lesions in the aortic arch and aortic root. Serum lipid and inflammatory factor levels were measured. Composition and diversity of gut microbiota were analyzed using targeted metabolomics, with a focus on the ratio of Firmicutes to Bacteroidetes. The expression of hepatic flavin-containing monooxygenase 3 (FMO3) and serum TMAO levels were also evaluated.<br><br>RESULTS: Mice receiving gut microbiota from CAP mice showed increased atherosclerotic lesions compared to controls, without significant differences in serum lipid or inflammatory factor levels. Alterations in gut microbiota composition were observed, characterized by an increase in the Firmicutes to Bacteroidetes ratio. Peptostreptococcaceae abundance positively correlated with atherosclerosis severity, while Odoribacteraceae showed a negative correlation. No significant differences were found in hepatic FMO3 expression or serum TMAO levels.<br><br>CONCLUSIONS: The study confirms the role of gut microbiota disruption in CAP-mediated atherosclerosis development, independent of serum lipid or TMAO levels. Alterations in gut microbiota composition, particularly increased Firmicutes to Bacteroidetes ratio and specific bacterial families, were associated with atherosclerosis severity. These findings highlight the intricate interplay between gut microbiota and cardiovascular health in the context of CAP.}, }
@article {pmid39612216, year = {2024}, author = {Wang, T and Luo, Y and Kong, X and Fang, L and Zhu, L and Yu, B and Zheng, P and Huang, Z and Mao, X and Jie, Y and Luo, J and Yan, H and He, J}, title = {Multiomics comparative analysis of feces AMRGs of Duroc pigs and Tibetan and the effect of fecal microbiota transplantation on AMRGs upon antibiotic exposure.}, journal = {Microbiology spectrum}, volume = {13}, number = {5}, pages = {e0198324}, pmid = {39612216}, issn = {2165-0497}, abstract = {UNLABELLED: Fecal matter is recognized as both a reservoir and a transmission source for various antimicrobial resistance genes (AMRGs). However, the transcriptional activity of AMRGs in swine feces is not well understood. In addition, the effect of fecal microbiota transplantation (FMT) on the excretion of AMRGs has rarely been reported. Our study explored the diversity, abundance, transcriptional activity, and bacterial hosts of AMRGs in Tibetan and Duroc pig feces using metagenomic and metatranscriptomic sequencing technologies. We discovered a significantly higher genomic abundance of AMRGs in the feces of Duroc pigs compared to Tibetan pigs (P < 0.001), although the transcript levels did not show a significant difference. The results showed that the core composition of AMRGs in pig feces varied considerably, with the most transcriptionally active AMRGs being oqxB, tetQ, Bla1, dfrA1, and amrB. Furthermore, the Firmicutes phylum is the main host of AMRGs. By transplanting fecal flora from Tibetan and Duroc pigs into the intestines of Duroc Landrace Yorkshire (DLY) piglets after acute antibiotic exposure, we found that only Tibetan pig fecal flora significantly reduced AMRGs in the feces of DLY piglets (P < 0.05). The effectiveness of Tibetan pig fecal microorganisms in removing AMRGs from DLY pig feces was mainly influenced by microbial communities, especially the Bacteroidota phylum. These findings offer valuable insights for the prevention and control of AMRG pollution.<br><br>IMPORTANCE: To the best of our knowledge, this study represents the first comprehensive analysis of antimicrobial resistance gene (AMRGs) expression in the fecal microbiota of Tibetan and Duroc pigs, employing an integrated metagenomic and metatranscriptomic approach. Our findings indicate a higher risk of AMRGs transmission in the feces of Duroc pigs compared to Tibetan pigs. Given the escalating antimicrobial resistance crisis, novel therapeutic interventions are imperative to mitigate gut colonization by pathogens and AMRGs. In this regard, we investigated the impact of fecal microbiota from Tibetan and Duroc pig sources on AMRGs excretion in Duroc Landrace Yorkshire (DLY) piglets' feces following acute antibiotic exposure. Remarkably, only fecal microbiota sourced from Tibetan pigs exhibited a reduction in AMRGs excretion in DLY piglets' feces. This underscores the significance of evaluating the presence of AMRGs within donor fecal microbiota for effective AMRGs decolonization strategies.}, }
@article {pmid39608831, year = {2024}, author = {Tang, JMF and Habib, F and Rahmdil, M and Apostolou, N}, title = {Autologous faecal microbiota transplantation via double barrel stoma to treat chronic diversion colitis.}, journal = {BMJ case reports}, volume = {17}, number = {11}, pages = {}, doi = {10.1136/bcr-2024-262806}, pmid = {39608831}, issn = {1757-790X}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis/therapy/microbiology/surgery ; *Ileostomy ; Male ; Transplantation, Autologous ; Middle Aged ; Treatment Outcome ; Chronic Disease ; Female ; }, abstract = {Diversion colitis is a common phenomenon affecting patients after defunctioning ileostomy. We present a complex case of diversion colitis where the patient was deemed unsuitable for restorative surgery due to multiple areas of stricturing in a long defunctioned colonic segment. Despite initial treatments with rectally administered topical mesalazine, butyrate enemas and topical steroid therapy, the patient remained symptomatic with rectal bleeding and mucus discharge. Furthermore, the appearance of colitis could be appreciated on endoscopy and radiological investigations with changes in histology consistent with moderate-severe diversion colitis. This article describes our experience in the use of autologous faecal transplant administered via the efferent loop of a double-barrel ileostomy to successfully treat diversion colitis refractory to standard topical therapy.}, }
@article {pmid39607629, year = {2025}, author = {Chua, HC and Pham, S and Lombardi, DA and Hot, E and Mody, L}, title = {Patient Satisfaction Scale Following a Laxative for Antibiotic Washout Prior to Oral Microbiome Therapy.}, journal = {Advances in therapy}, volume = {42}, number = {1}, pages = {490-499}, pmid = {39607629}, issn = {1865-8652}, mesh = {Humans ; *Patient Satisfaction ; *Laxatives/administration &amp; dosage/therapeutic use ; Male ; Female ; Middle Aged ; *Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; Aged ; Adult ; Psychometrics ; Reproducibility of Results ; Administration, Oral ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/prevention &amp; control ; Surveys and Questionnaires ; }, abstract = {INTRODUCTION: Administration of fecal microbiota spores, live-brpk [Vowst Oral Spores (VOS)], an oral microbiome therapeutic approved for prevention of recurrent Clostridioides difficile infection in adults, requires antibiotic washout using a laxative prior to administration. Patient acceptability of the prerequisite laxative is important. This study assessed psychometric properties of the Antibiotic Washout Patient Satisfaction Scale (AWPSS) which was minimally modified from a previously validated patient satisfaction scale for bowel preparation prior to colonoscopy.<br><br>METHODS: Patients from the ECOSPOR IV trial who received a laxative preparation prior to oral administration of VOS and were administered the AWPSS were included. Reliability and construct validity of the AWPSS were evaluated.<br><br>RESULTS: AWPSS data were available for 110 patients; all completed all 6 items of the AWPSS, supporting its acceptability. Domain 1 mean/median transformed total scores of 105.9/100 [range (best-worst), 0-300] suggested that patients were satisfied with the laxative preparation; a Cronbach's alpha of 0.81 showed acceptable reliability. Almost all patients (97.3%) reported they were able to consume the entire laxative solution as instructed and would take it again if needed (95.5%). Higher satisfaction with the laxative preparation predicted higher acceptability of future use if needed (lower score) with mean/median of 101.7/100 and 195.0/200.00 for those who were willing or not willing to accept, respectively (P&#xa0;=&#xa0;0.008).<br><br>CONCLUSIONS: AWPSS is a valid and reliable 6-item patient-reported outcome measure for use in patients requiring a laxative prior to oral microbiome therapy. AWPSS showed antibiotic washout was well tolerated and predicted that patients would be willing to consume the laxative in the future if needed.}, }
@article {pmid39607612, year = {2024}, author = {Qasem, HH and El-Sayed, WM}, title = {The bacterial microbiome and cancer: development, diagnosis, treatment, and future directions.}, journal = {Clinical and experimental medicine}, volume = {25}, number = {1}, pages = {12}, pmid = {39607612}, issn = {1591-9528}, mesh = {Humans ; *Neoplasms/therapy/microbiology/diagnosis ; *Dysbiosis ; *Microbiota ; Bacteria/classification/genetics ; Probiotics/therapeutic use ; }, abstract = {The term "microbiome" refers to the collection of bacterial species that reside in the human body's tissues. Sometimes, it is used to refer to all microbial entities (bacteria, viruses, fungi, and others) which colonize the human body. It is now generally acknowledged that the microbiome plays a critical role in the host's physiological processes and general well-being. Changes in the structure and/or function of the microbiome (dysbiosis) are linked to the development of many diseases including cancer. The claim that because of their negatively charged membrane, cancer cells are more vulnerable to some bacteria than normal cells and that is how the link between these bacteria and cancer evolved has been refuted. Furthermore, the relationship between the microbiome and cancer is more evident in the emerging field of cancer immunotherapy. In this narrative review, we detailed the correlation between the presence/absence of specific bacterial species and the development, diagnosis, prognosis, and treatment of some types of cancer including colorectal, lung, breast, and prostate cancer. In addition, we discussed the mechanisms of microbiome-cancer interactions including genotoxin production, the role of free radicals, modification of signaling pathways in host cells, immune modulation, and modulation of drug metabolism by microbiome. Future directions and clinical application of microbiome in the early detection, prognosis, and treatment of cancer emphasizing on the role of fecal transplantation, probiotics, prebiotics, and microbiome biomarkers were also considered.}, }
@article {pmid39606629, year = {2024}, author = {Zhang, Z and Yang, M and Zhou, T and Chen, Y and Zhou, X and Long, K}, title = {Emerging trends and hotspots in intestinal microbiota research in sepsis: bibliometric analysis.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1510463}, pmid = {39606629}, issn = {2296-858X}, abstract = {BACKGROUND: The association between the gut microbiota and sepsis has garnered attention in the field of intestinal research in sepsis. This study utilizes bibliometric methods to visualize and analyze the literature on gut microbiota research in sepsis from 2011 to 2024, providing a scientific foundation for research directions and key issues in this domain.<br><br>METHODS: Original articles and reviews of gut microbiota research in sepsis, which published in English between 2011 and 2024, were obtained from the Web of Science Core Collection on June 21, 2024. Python, VOSviewer, and CiteSpace software were used for the visual analysis of the retrieved data.<br><br>RESULTS: A total of 1,031 articles were analyzed, originating from 72 countries or regions, 1,614 research institutions, and 6,541 authors. The articles were published in 434 different journals, covering 89 different research fields. The number of publications and citations in this research area showed a significant growth trend from 2011 to 2024, with China, the United States, and the United Kingdom being the main research forces. Asada Leelahavanichkul from Thailand was identified as the most prolific author, making him the most authoritative expert in this field. "Nutrients" had the highest number of publications, while "Frontiers in Cellular and Infection Microbiology," "Frontiers in Immunology" and "the International Journal of Molecular Sciences" have shown increasing attention to this field in the past 2&#x2009;years. Author keywords appearing more than 100 times included "gut microbiota (GM)," "sepsis" and "microbiota." Finally, this study identified "lipopolysaccharides (LPS)," "short-chain fatty acids (SCFAs)," "probiotics," "fecal microbiota transplantation (FMT)" and "gut-liver axis" as the research hotspots and potential frontier directions in this field.<br><br>CONCLUSION: This bibliometric study summarizes current important perspectives and offers comprehensive guidance between sepsis and intestinal microbiota, which may help researchers choose the most appropriate research directions.}, }
@article {pmid39605286, year = {2024}, author = {Yerushalmy-Feler, A and Spencer, EA and Dolinger, MT and Suskind, DL and Mitrova, K and Hradsky, O and Conrad, MA and Kelsen, JR and Uhlig, HH and Tzivinikos, C and Ancona, S and Wlazlo, M and Hackl, L and Shouval, DS and Bramuzzo, M and Urlep, D and Olbjorn, C and D'Arcangelo, G and Pujol-Muncunill, G and Yogev, D and Kang, B and Gasparetto, M and Rungø, C and Kolho, KL and Hojsak, I and Norsa, L and Rinawi, F and Sansotta, N and Magen Rimon, R and Granot, M and Scarallo, L and Trindade, E and Velasco Rodríguez-Belvís, M and Turner, D and Cohen, S}, title = {Upadacitinib for Induction of Remission in Pediatric Ulcerative Colitis: An International Multi‑center Study.}, journal = {Journal of Crohn's &amp; colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjae182}, pmid = {39605286}, issn = {1876-4479}, abstract = {BACKGROUND AND AIMS: Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U.<br><br>METHODS: In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical and laboratory data as well as adverse events (AEs) were recorded at week 8 post induction.<br><br>RESULTS: One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3-17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with &#x2265;2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. AEs were recorded in 37 children, including one serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n=13), acne (n=12), and infections (n=10, five of whom with herpes viruses).<br><br>CONCLUSION: Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.}, }
@article {pmid39605077, year = {2024}, author = {Zou, P and Bi, Y and Tong, Z and Wu, T and Li, Q and Wang, K and Fan, Y and Zhao, D and Wang, X and Shao, H and Huang, H and Ma, S and Qian, Y and Zhang, G and Liu, X and Jin, Q and Ru, Q and Qian, Z and Sun, W and Chen, Q and You, L and Wang, F and Zhang, X and Qiu, Z and Lin, Q and Lv, J and Zhang, Y and Geng, J and Mao, R and Liu, J and Zheng, Y and Ding, F and Wang, H and Gao, H}, title = {Comparisons of efficacy and safety of 400 or 800 ml bacterial count fecal microbiota transplantation in the treatment of recurrent hepatic encephalopathy: a multicenter prospective randomized controlled trial in China.}, journal = {Trials}, volume = {25}, number = {1}, pages = {799}, pmid = {39605077}, issn = {1745-6215}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Bacterial Load ; China ; *Fecal Microbiota Transplantation/adverse effects ; *Hepatic Encephalopathy/therapy/microbiology ; Multicenter Studies as Topic ; Prospective Studies ; Quality of Life ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Hepatic encephalopathy (HE) represents a critical complications of end-stage liver disease, serving as an independent predictor of mortality among patients with cirrhosis. Despite effective treatment with rifaximin, some patients with HE still progress to recurrent episodes, posing a significant therapeutic challenge. Recurrent HE is defined as experiencing two or more episodes within a 6-month period. Previous research has suggested that FMT may emerge as a promising treatment for recurrent HE. However, there remains a critical need to explore the optimal dosage. This trial aims to abscess the efficacy and safety of two FMT dosages: 800 ml or 400 ml total bacterial count, including mortality and quality of life.<br><br>METHODS: This multicenter, prospective, randomized controlled trial will enroll 100 eligible patients from 31 hospitals in China. Participants will be randomly assigned in a 1:1 ratio to either the high-dose group (800&#xa0;ml total bacterial count) or the low-dose group (400&#xa0;ml total bacterial count). The primary objective is to assess the efficacy and safety of both dosages on outcomes at 24 and 48&#xa0;weeks, including mortality and quality of life.<br><br>DISCUSSION: If either or both dosages of FMT demonstrate safe and effective treatment of recurrent HE, leading to improve quality of life and survival at 24 and 48&#xa0;weeks, this trial would address a significant gap in the management of recurrent HE, carrying innovative and clinically significant implications.<br><br>TRIAL REGISTRATION: NCT05669651 on ClinicalTrials.gov. Registered on 29 December 2022. CHiCTR2200067135 on China Registered Clinical Trial Registration Center. Registered on 27 December 2022.}, }
@article {pmid39604726, year = {2025}, author = {Chen-Liaw, A and Aggarwala, V and Mogno, I and Haifer, C and Li, Z and Eggers, J and Helmus, D and Hart, A and Wehkamp, J and Lamousé-Smith, ESN and Kerby, RL and Rey, FE and Colombel, JF and Kamm, MA and Olle, B and Norman, JM and Menon, R and Watson, AR and Crossette, E and Terveer, EM and Keller, JJ and Borody, TJ and Grinspan, A and Paramsothy, S and Kaakoush, NO and Dubinsky, MC and Faith, JJ}, title = {Gut microbiota strain richness is species specific and affects engraftment.}, journal = {Nature}, volume = {637}, number = {8045}, pages = {422-429}, pmid = {39604726}, issn = {1476-4687}, support = {R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Bacteria/classification/genetics/isolation &amp; purification ; Biodiversity ; *Fecal Microbiota Transplantation ; *Feces/microbiology ; *Gastrointestinal Microbiome ; Lakes/microbiology ; Metagenome ; Soil Microbiology ; *Species Specificity ; }, abstract = {Despite the fundamental role of bacterial strain variation in gut microbiota function[1-6], the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments. Active therapeutic administration of supraphysiologic numbers of strains per species increases recipient SR, which then converges back to the population average after dosing is ceased. Stratifying engraftment outcomes by high or low SR shows that SR predicts microbial addition or replacement in faecal transplants. Together, these results indicate that properties of the gut ecosystem govern the number of strains of each species colonizing the gut and thereby influence strain addition and replacement in faecal microbiota transplantation and defined live biotherapeutic products.}, }
@article {pmid39604623, year = {2024}, author = {Procházková, N and Laursen, MF and La Barbera, G and Tsekitsidi, E and Jørgensen, MS and Rasmussen, MA and Raes, J and Licht, TR and Dragsted, LO and Roager, HM}, title = {Gut physiology and environment explain variations in human gut microbiome composition and metabolism.}, journal = {Nature microbiology}, volume = {9}, number = {12}, pages = {3210-3225}, pmid = {39604623}, issn = {2058-5276}, support = {NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Bacteria/classification/metabolism/genetics/isolation &amp; purification ; Diet ; Feces/microbiology ; Fermentation ; *Gastrointestinal Microbiome/physiology ; *Gastrointestinal Tract/microbiology/physiology ; Gastrointestinal Transit/physiology ; Healthy Volunteers ; Hydrogen-Ion Concentration ; Methane/metabolism ; }, abstract = {The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days. We assessed day-to-day changes in gut environmental factors and measured whole-gut and segmental intestinal transit time and pH using a wireless motility capsule in a subset of 50 individuals. We observed substantial daily fluctuations, with intra-individual variations in gut microbiome and metabolism associated with changes in stool moisture and faecal pH, and inter-individual variations accounted for by whole-gut and segmental transit times and pH. Metabolites derived from microbial carbohydrate fermentation correlated negatively with the gut passage time and pH, while proteolytic metabolites and breath methane showed a positive correlation. Finally, we identified associations between segmental transit time/pH and coffee-, diet-, host- and microbial-derived metabolites. Our work suggests that gut physiology and environment are key to understanding the individuality of the human gut microbial composition and metabolism.}, }
@article {pmid39604327, year = {2025}, author = {Saeed, H and Díaz, LA and Gil-Gómez, A and Burton, J and Bajaj, JS and Romero-Gomez, M and Arrese, M and Arab, JP and Khan, MQ}, title = {Microbiome-centered therapies for the management of metabolic dysfunction-associated steatotic liver disease.}, journal = {Clinical and molecular hepatology}, volume = {31}, number = {Suppl}, pages = {S94-S111}, pmid = {39604327}, issn = {2287-285X}, support = {1241450//Fondo Nacional de Desarrollo Cient&#xed;fico y Tecnol&#xf3;gico/ ; CD23-00024//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Fatty Liver/therapy/microbiology ; Prebiotics ; Dysbiosis ; Synbiotics ; Phage Therapy ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus. This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies' potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.}, }
@article {pmid39603188, year = {2025}, author = {Xie, C and Liang, Q and Cheng, J and Yuan, Y and Xie, L and Ji, J}, title = {Transplantation of fecal microbiota from low to high residual feed intake chickens: Impacts on RFI, microbial community and metabolites profiles.}, journal = {Poultry science}, volume = {104}, number = {1}, pages = {104567}, pmid = {39603188}, issn = {1525-3171}, mesh = {Animals ; *Chickens/physiology/microbiology/genetics ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/veterinary ; Feces/microbiology ; Animal Feed/analysis ; *Metabolome ; Male ; *Eating ; Female ; RNA, Ribosomal, 16S/analysis ; Animal Nutritional Physiological Phenomena ; }, abstract = {Improving feed efficiency is vital to bolster profitability and sustainability in poultry production. Although several studies have established links between gut microbiota and feed efficiency, the direct effects remain unclear. In this study, two distinct lines of Huiyang bearded chickens, exhibiting significant differences in residual feed intake (RFI), were developed after 15 generations of selective breeding. Fecal microbiota transplantation (FMT) from low RFI (LRFI) chickens to high RFI (HRFI) chickens resulted in a reduction trend in RFI, decreasing from 5.65 to 4.49 in the HRFI recipient chickens (HFMT). Microbiota composition and functional profiles in LRFI and HFMT chickens formed a distinct cluster compared to HRFI chickens. Using 16S rDNA sequencing and RandomForest analysis, Slackia, Peptococcus, Blautia, and Dorea were identified as key microbial markers associated with feed efficiency. Additionally, untargeted metabolomics identified common differential metabolites between HFMT and LRFI vs. HRFI groups. Correlation analysis showed significant correlations between these microbial markers and differential metabolites. These findings provide a foundation for microbiome-based strategies to improve feed efficiency in poultry.}, }
@article {pmid39600755, year = {2024}, author = {Castro-Vidal, ZA and Mathew, F and Ibrahim, AA and Shubhangi, F and Cherian, RR and Choi, HK and Begum, A and Ravula, HK and Giri, H}, title = {The Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Various Neurocognitive Disorders.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72451}, pmid = {39600755}, issn = {2168-8184}, abstract = {This review explores the critical role of the human microbiome in neurological and neurodegenerative disorders, focusing on gut-brain axis dysfunction caused by dysbiosis, an imbalance in gut bacteria. Dysbiosis has been linked to diseases such as Alzheimer's disease, Parkinson's disease (PD), multiple sclerosis (MS), and stroke. The gut microbiome influences the central nervous system (CNS) through signaling molecules, including short-chain fatty acids, neurotransmitters, and metabolites, impacting brain health and disease progression. Emerging therapies, such as fecal microbiota transplantation (FMT), have shown promise in restoring microbial balance and alleviating neurological symptoms, especially in Alzheimer's and PD. Additionally, nutritional interventions such as probiotics, prebiotics, and specialized diets are being investigated for their ability to modify gut microbiota and improve patient outcomes. This review highlights the therapeutic potential of gut microbiota modulation but emphasizes the need for further clinical trials to establish the safety and efficacy of these interventions in neurological and mental health disorders.}, }
@article {pmid39600698, year = {2024}, author = {Liu, X and Li, B and Liang, L and Han, J and Mai, S and Liu, L}, title = {From microbes to medicine: harnessing the power of the microbiome in esophageal cancer.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1450927}, pmid = {39600698}, issn = {1664-3224}, mesh = {Humans ; *Esophageal Neoplasms/therapy/microbiology/immunology ; *Dysbiosis/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; Animals ; Probiotics/therapeutic use ; Microbiota/immunology ; }, abstract = {Esophageal cancer (EC) is a malignancy with a high incidence and poor prognosis, significantly influenced by dysbiosis in the esophageal, oral, and gut microbiota. This review provides an overview of the roles of microbiota dysbiosis in EC pathogenesis, emphasizing their impact on tumor progression, drug efficacy, biomarker discovery, and therapeutic interventions. Lifestyle factors like smoking, alcohol consumption, and betel nut use are major contributors to dysbiosis and EC development. Recent studies utilizing advanced sequencing have revealed complex interactions between microbiota dysbiosis and EC, with oral pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum promoting inflammation and suppressing immune responses, thereby driving carcinogenesis. Altered esophageal microbiota, characterized by reduced beneficial bacteria and increased pathogenic species, further exacerbate local inflammation and tumor growth. Gut microbiota dysbiosis also affects systemic immunity, influencing chemotherapy and immunotherapy efficacy, with certain bacteria enhancing or inhibiting treatment responses. Microbiota composition shows potential as a non-invasive biomarker for early detection, prognosis, and personalized therapy. Novel therapeutic strategies targeting the microbiota-such as probiotics, dietary modifications, and fecal microbiota transplantation-offer promising avenues to restore balance and improve treatment efficacy, potentially enhancing patient outcomes. Integrating microbiome-focused strategies into current therapeutic frameworks could improve EC management, reduce adverse effects, and enhance patient survival. These findings highlight the need for further research into microbiota-tumor interactions and microbial interventions to transform EC treatment and prevention, particularly in cases of late-stage diagnosis and poor treatment response.}, }
@article {pmid39600557, year = {2024}, author = {Wohl, P and Krausova, A and Wohl, P and Fabian, O and Bajer, L and Brezina, J and Drastich, P and Hlavaty, M and Novotna, P and Kahle, M and Spicak, J and Gregor, M}, title = {Limited validity of Mayo endoscopic subscore in ulcerative colitis with concomitant primary sclerosing cholangitis.}, journal = {World journal of gastrointestinal endoscopy}, volume = {16}, number = {11}, pages = {607-616}, pmid = {39600557}, issn = {1948-5190}, abstract = {BACKGROUND: Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear.<br><br>AIM: To assess the accuracy of MES in UC and PSC-UC patients, we performed histological scoring using Nancy histological index (NHI).<br><br>METHODS: MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy. NHI and inflammation were evaluated in biopsies from the cecum, rectum, and terminal ileum. In addition, perinuclear anti-neutrophil cytoplasmic antibodies, fecal calprotectin, body mass index, and other relevant clinical characteristics were collected.<br><br>RESULTS: The median MES and NHI were similar for UC patients (MES grade 2 and NHI grade 2 in the rectum) but were different for PSC-UC patients (MES grade 0 and NHI grade 2 in the cecum). There was a correlation between MES and NHI for UC patients (Spearman's r = 0.40, P = 0.029) but not for PSC-UC patients. Histopathological examination revealed persistent microscopic inflammation in 88% of PSC-UC patients with MES grade 0 (46% of all PSC-UC patients). Moreover, MES overestimated the severity of active inflammation in an additional 11% of PSC-UC patients.<br><br>CONCLUSION: MES insufficiently identifies microscopic inflammation in PSC-UC. This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.}, }
@article {pmid39599742, year = {2024}, author = {Al-Habsi, N and Al-Khalili, M and Haque, SA and Elias, M and Olqi, NA and Al Uraimi, T}, title = {Health Benefits of Prebiotics, Probiotics, Synbiotics, and Postbiotics.}, journal = {Nutrients}, volume = {16}, number = {22}, pages = {}, pmid = {39599742}, issn = {2072-6643}, support = {(SR/AGR/Food/23/01)//His Majesty Trust Funds/ ; }, mesh = {Humans ; *Prebiotics/administration &amp; dosage ; *Probiotics/administration &amp; dosage ; *Synbiotics/administration &amp; dosage ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Functional Food ; }, abstract = {The trillions of microbes that constitute the human gut microbiome play a crucial role in digestive health, immune response regulation, and psychological wellness. Maintaining gut microbiota is essential as metabolic diseases are associated with it. Functional food ingredients potentially improving gut health include prebiotics, probiotics, synbiotics, and postbiotics (PPSPs). While probiotics are living bacteria that provide health advantages when ingested sufficiently, prebiotics are non-digestible carbohydrates that support good gut bacteria. Synbiotics work together to improve immunity and intestinal health by combining probiotics and prebiotics. Postbiotics have also demonstrated numerous health advantages, such as bioactive molecules created during probiotic fermentation. According to a recent study, PPSPs can regulate the synthesis of metabolites, improve the integrity of the intestinal barrier, and change the gut microbiota composition to control metabolic illnesses. Additionally, the use of fecal microbiota transplantation (FMT) highlights the potential for restoring gut health through microbiota modulation, reinforcing the benefits of PPSPs in enhancing overall well-being. Research has shown that PPSPs provide several health benefits, such as improved immunological function, alleviation of symptoms associated with irritable bowel disease (IBD), decreased severity of allergies, and antibacterial and anti-inflammatory effects. Despite encouraging results, many unanswered questions remain about the scope of PPSPs' health advantages. Extensive research is required to fully realize the potential of these functional food components in enhancing human health and well-being. Effective therapeutic and prophylactic measures require further investigation into the roles of PPSPs, specifically their immune-system-modulating, cholesterol-lowering, antioxidant, and anti-inflammatory characteristics.}, }
@article {pmid39598283, year = {2024}, author = {Mederle, AL and Dima, M and Stoicescu, ER and Căpăstraru, BF and Levai, CM and Hațegan, OA and Maghiari, AL}, title = {Impact of Gut Microbiome Interventions on Glucose and Lipid Metabolism in Metabolic Diseases: A Systematic Review and Meta-Analysis.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {39598283}, issn = {2075-1729}, abstract = {BACKGROUND: The gut microbiome is increasingly recognized as a key player in metabolic health, influencing glucose and lipid metabolism through various mechanisms. However, the efficacy of gut microbiota-targeted interventions, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and diet-based treatments, remains unclear for specific metabolic outcomes. In this study, the aim was to evaluate the impact of these interventions on the glucose and lipid parameters in individuals with metabolic diseases such as diabetes mellitus (DM), obesity, and metabolic syndrome.<br><br>METHODS: This systematic review and meta-analysis included 41 randomized controlled trials that investigated the effects of gut microbiota-targeted treatments on metabolic parameters such as fasting glucose, glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. A comprehensive search was conducted using databases like PubMed, Google Scholar, and Scopus, focusing on interventions targeting the gut microbiota. A meta-analysis was performed using random-effects models, with effect sizes calculated for each outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool.<br><br>RESULTS: Gut microbiota-targeted interventions significantly reduced fasting glucose, HbA1c, HOMA-IR, total cholesterol, LDL-C, and triglycerides, with moderate heterogeneity observed across studies. The interventions also led to modest increases in HDL-C levels. Probiotic and synbiotic interventions showed the most consistent benefits in improving both glucose and lipid profiles, while FMT yielded mixed results. Short-term interventions showed rapid microbial shifts but less pronounced metabolic improvements, whereas longer-term interventions had more substantial metabolic benefits.<br><br>CONCLUSIONS: In this study, it is demonstrated that gut microbiota-targeted interventions can improve key metabolic outcomes, offering a potential therapeutic strategy for managing metabolic diseases. However, the effectiveness of these interventions varies depending on the type, duration, and population characteristics, highlighting the need for further long-term studies to assess the sustained effects of microbiota modulation on metabolic health.}, }
@article {pmid39597729, year = {2024}, author = {Alexandrescu, L and Suceveanu, AP and Stanigut, AM and Tofolean, DE and Axelerad, AD and Iordache, IE and Herlo, A and Nelson Twakor, A and Nicoara, AD and Tocia, C and Dumitru, A and Dumitru, E and Condur, LM and Aftenie, CF and Tofolean, IT}, title = {Intestinal Insights: The Gut Microbiome's Role in Atherosclerotic Disease: A Narrative Review.}, journal = {Microorganisms}, volume = {12}, number = {11}, pages = {}, pmid = {39597729}, issn = {2076-2607}, abstract = {Recent advances have highlighted the gut microbiota as a significant contributor to the development and progression of atherosclerosis, which is an inflammatory cardiovascular disease (CVD) characterized by plaque buildup within arterial walls. The gut microbiota, consisting of a diverse collection of microorganisms, impacts the host's metabolism, immune responses, and lipid processing, all of which contribute to atherosclerosis. This review explores the complex mechanisms through which gut dysbiosis promotes atherogenesis. We emphasize the potential of integrating microbiota modulation with traditional cardiovascular care, offering a holistic approach to managing atherosclerosis. Important pathways involve the translocation of inflammatory microbial components, modulation of lipid metabolism through metabolites such as trimethylamine-N-oxide (TMAO), and the production of short-chain fatty acids (SCFAs) that influence vascular health. Studies reveal distinct microbial profiles in atherosclerosis patients, with increased pathogenic bacteria (Megamonas, Veillonella, Streptococcus) and reduced anti-inflammatory genera (Bifidobacterium, Roseburia), highlighting the potential of these profiles as biomarkers and therapeutic targets. Probiotics are live microorganisms that have health benefits on the host. Prebiotics are non-digestible dietary fibers that stimulate the growth and activity of beneficial gut bacteria. Interventions targeting microbiota, such as probiotics, prebiotics, dietary modifications, and faecal microbiota transplantation (FMT), present effective approaches for restoring microbial equilibrium and justifying cardiovascular risk. Future research should focus on longitudinal, multi-omics studies to clarify causal links and refine therapeutic applications.}, }
@article {pmid39597606, year = {2024}, author = {Qiao, Y and Feng, Q and Wang, Q and Zhao, Q and Zhu, S and Zhao, F and Wang, Z and Zhang, R and Wang, J and Yu, Y and Han, H and Dong, H}, title = {Alteration in the Gut Microbiota of Chickens Resistant to Eimeria tenella Infection.}, journal = {Microorganisms}, volume = {12}, number = {11}, pages = {}, pmid = {39597606}, issn = {2076-2607}, support = {Grant No. 2023YFD18024//National Key Research and Development Program of China/ ; XZ202401ZY0052//Key Research and Development of Science and Technology Plan in Tibet Autonomous Region/ ; Grant No. 32373038//National Natural Science Foundation of China/ ; NPRC-2019-194-30//National Parasitic Resources Center/ ; }, abstract = {Avian coccidiosis, caused by several species of Eimeria, is a widespread and economically important poultry disease that inflicts severe losses in the poultry industry. Understanding the interplay between Eimeria and gut microbiota is critical for controlling coccidiosis and developing innovative treatments to ensure good poultry health. In the present study, chickens were immunized six times with a low dose of Eimeria tenella, resulting in complete immunity against Eimeria infection. The results of fecal microbiota transplantation showed that the gut microbiota of immunized chickens induced a certain degree of resistance to coccidial infection. To investigate the types of intestinal microbiota involved in the development of resistance to Eimeria, the intestinal contents and fecal samples from both immunized and unimmunized groups were collected for 16S rRNA gene sequencing. The results showed that, at the genus level, the abundance of the Eubacterium coprostanoligenes group, Erysipelatoclostridium, Shuttleworthia, and Colidextribacter was significantly increased in the intestinal content of immunized chickens, whereas the abundance of Eisenbergiella was significantly decreased. In fecal samples, the abundance of Clostridiaceae and Muribaculaceae significantly increased, whereas that of Bacillales significantly decreased. These findings will help to elucidate the interactions between E. tenella and the gut microbiota of chickens, providing a basis for isolating E. tenella-resistant strains from the gut microbiome and developing new vaccines against coccidiosis.}, }
@article {pmid39597084, year = {2024}, author = {Ko, Y and Alaedin, S and Fernando, D and Zhou, J and Ho, V}, title = {A Review of Fecal Microbiota Transplantation in Children-Exploring Its Role in the Treatment of Inflammatory Bowel Diseases.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {11}, pages = {}, pmid = {39597084}, issn = {1648-9144}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Child ; *Inflammatory Bowel Diseases/therapy/microbiology ; Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {Background and Objectives: There is an increasing use of fecal matter transplantation (FMT) worldwide as research into the impact of the gut microbiome in various disease states is growing. FMT is the transfer of stool from a healthy human donor to a patient for the purpose of restoring intestinal dysbiosis. This review will assess the efficacy and safety of FMT in the treatment of pediatric inflammatory bowel diseases (IBDs) and explore the future directions of the use of FMT in children. Materials and Methods: A systematic review was performed where a literature search of publications published prior to 15 September 2023 was performed. Efficacy outcomes and safety data as well as microbiome analysis were reviewed from the studies where applicable. Results: Nine studies on UC and two studies on CD satisfied eligibility criteria and individually analysed. Most of the studies provided microbiome analyses. Conclusions: FMT is a safe treatment for paediatric IBD, and is shown to be effective in inducing clinical response by some studies. However the lack of randomized controlled trials limited the results of our study.}, }
@article {pmid39596154, year = {2024}, author = {Sevcikova, A and Martiniakova, M and Omelka, R and Stevurkova, V and Ciernikova, S}, title = {The Link Between the Gut Microbiome and Bone Metastasis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {22}, pages = {}, pmid = {39596154}, issn = {1422-0067}, support = {2/0069/22//Scientific Grant Agency of the Ministry of Education, Research, Development, and Youth of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; 1/0071/24//Scientific Grant Agency of the Ministry of Education, Research, Development, and Youth of the Slovak Republic and Slovak Academy of Sciences/ ; KEGA 034UKF-4/2022//Ministry of Education, Research, Development, and Youth of the Slovak Republic/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Bone Neoplasms/secondary/microbiology ; Animals ; Dysbiosis/microbiology ; Probiotics ; }, abstract = {The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host's immune system. Mounting evidence highlights that disruption in gut microbial communities significantly impacts cancer development and treatment. Moreover, tumor-associated microbiota, along with its metabolites and toxins, may contribute to cancer progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and metastatic spread to distant organs. Bones, in particular, are common sites for metastasis due to a rich supply of growth and neovascularization factors and extensive blood flow, especially affecting patients with thyroid, prostate, breast, lung, and kidney cancers, where bone metastases severely reduce the quality of life. While the involvement of the gut microbiome in bone metastasis formation is still being explored, proposed mechanisms suggest that intestinal dysbiosis may alter the bone microenvironment via the gut-immune-bone axis, fostering a premetastatic niche and immunosuppressive milieu suitable for cancer cell colonization. Disruption in the delicate balance of bone modeling and remodeling may further create a favorable environment for metastatic growth. This review focuses on the link between beneficial or dysbiotic microbiome composition and bone homeostasis, as well as the role of the microbiome in bone metastasis development. It also provides an overview of clinical trials evaluating the impact of gut microbial community structure on bone parameters across various conditions or health-related issues. Dietary interventions and microbiota modulation via probiotics, prebiotics, and fecal microbiota transplantation help support bone health and might offer promising strategies for addressing bone-related complications in cancer.}, }
@article {pmid39595097, year = {2024}, author = {López-Tenorio, II and Aguilar-Villegas, &#xd3;R and Espinoza-Palacios, Y and Segura-Real, L and Peña-Aparicio, B and Amedei, A and Aguirre-García, MM}, title = {Primary Prevention Strategy for Non-Communicable Diseases (NCDs) and Their Risk Factors: The Role of Intestinal Microbiota.}, journal = {Biomedicines}, volume = {12}, number = {11}, pages = {}, pmid = {39595097}, issn = {2227-9059}, support = {CF 2023-2024 -734//Consejo Nacional de Humanidades, Ciencias y Tecnolog&#xed;as/ ; IN21222//Universidad Nacional Aut&#xf3;noma de M&#xe9;xico/ ; }, abstract = {Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. These conditions have numerous health consequences and significantly impact patients' lifestyles. Effective long-term treatment is essential since NCDs are irreversible. Therefore, primary healthcare must be both exclusive and of the highest quality, ensuring comprehensive care. The primary goal should be to improve quality of life with a focus on patients, families, and communities, as most of these diseases can be prevented and controlled, although not cured. Several factors have been linked to individual health, including social, cultural, and economic aspects, lifestyle, and certain environmental factors, including work, that can have positive or negative effects. More of these variables may contribute to the onset of NCDs, which are defined by their chronic nature, propensity for prolongation, and generally slow rate of progression. Examples of NCDs include hypertension, type 2 diabetes (T2D), dyslipidemia, and fatty liver disease linked to metabolic dysfunction. The onset of these diseases has been associated with an imbalance in certain microbial niches, such as the gut, which hosts billions of microorganisms performing multiple metabolic functions, such as the production of metabolites like bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). Therefore, lifestyle changes and personal habits can significantly impact the gut microbiota (GM), potentially preventing chronic diseases associated with metabolism. NCDs are highly prevalent worldwide, prompting increased attention to strategies for modifying the intestinal microbiota (IM). Approaches such as probiotics, prebiotics, synbiotics, and fecal transplantation (FMT) have demonstrated improvements in the quality of life for individuals with these conditions. Additionally, lifestyle changes and the adoption of healthy habits can significantly impact IM and may help prevent chronic diseases related to metabolism. Therefore, the main aim of this review is to analyze and understand the importance of microbiota intervention in the prevention of non-communicable diseases. R3:A1.}, }
@article {pmid39594528, year = {2024}, author = {Scarpellini, E and Scarcella, M and Tack, JF and Scarlata, GGM and Zanetti, M and Abenavoli, L}, title = {Gut Microbiota and Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, pmid = {39594528}, issn = {2076-3921}, abstract = {Background: The gut microbiota constitutes a complex microorganism community that harbors bacteria, viruses, fungi, protozoa, and archaea. The human gut bacterial microbiota has been extensively proven to participate in human metabolism, immunity, and nutrient absorption. Its imbalance, namely "dysbiosis", has been linked to disordered metabolism. Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the features of deranged human metabolism and is the leading cause of liver cirrhosis and hepatocellular carcinoma. Thus, there is a pathophysiological link between gut dysbiosis and MASLD. Aims and Methods: We aimed to review the literature data on the composition of the human bacterial gut microbiota and its dysbiosis in MASLD and describe the concept of the "gut-liver axis". Moreover, we reviewed the approaches for gut microbiota modulation in MASLD treatment. Results: There is consolidated evidence of particular gut dysbiosis associated with MASLD and its stages. The model explaining the relationship between gut microbiota and the liver has a bidirectional organization, explaining the physiopathology of MASLD. Oxidative stress is one of the keystones in the pathophysiology of MASLD and fibrosis generation. There is promising and consolidated evidence for the efficacy of pre- and probiotics in reversing gut dysbiosis in MASLD patients, with therapeutic effects. Few yet encouraging data on fecal microbiota transplantation (FMT) in MASLD are available in the literature. Conclusions: The gut dysbiosis characteristic of MASLD is a key target in its reversal and treatment via diet, pre/probiotics, and FMT treatment. Oxidative stress modulation remains a promising target for MASLD treatment, prevention, and reversal.}, }
@article {pmid39593402, year = {2024}, author = {Tian, B and Pan, Y and Zhang, X and Wu, Y and Luo, X and Yang, K}, title = {Etiolated-green tea attenuates colonic barrier dysfunction and inflammation in high-fat diet-induced mice by modulating gut microbiota.}, journal = {Food research international (Ottawa, Ont.)}, volume = {197}, number = {Pt 1}, pages = {115192}, doi = {10.1016/j.foodres.2024.115192}, pmid = {39593402}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diet, High-Fat/adverse effects ; *Tea/chemistry ; Mice ; Male ; *Colon/microbiology/metabolism/drug effects ; *Mice, Inbred C57BL ; *Inflammation ; Fatty Acids, Volatile/metabolism ; Dysbiosis ; Obesity/metabolism ; NF-kappa B/metabolism ; Intestinal Mucosa/metabolism/drug effects ; Fecal Microbiota Transplantation ; Toll-Like Receptor 4/metabolism ; Signal Transduction/drug effects ; Receptors, G-Protein-Coupled/metabolism ; Tight Junctions/drug effects/metabolism ; }, abstract = {Colonic barrier dysfunction and inflammation arising from dysbiosis gut microbiota (GM) are strongly associated with a high-fat diet (HFD). Yellow leaf green tea (YLGT), a novel variety of etiolated-green tea, improving the intestinal barrier and inflammation is related to the regulation of GM disorders. To explore the ameliorative mechanism of YLGT, mice were fed an HFD with or without YLGT at doses of 150, 300, and 450 mg kg[-1] for 12 weeks. YLGT rectified the GM imbalance, enriched short-chain fatty acid (SCFA)-producing bacteria and gut SCFA contents, activated G protein-coupled receptors, inhibited TLR4/NF-κB signaling pathway, strengthened the tight junction, and repaired the damaged intestinal barrier. The fecal microbiota transplantation experiment further confirmed that the GM was a key element in the anti-obesity and anti-intestinal inflammation effect of YLGT. YLGT has great promise in attenuating obesity-induced intestinal dysfunction. This research provides novel insights into the new mechanism of YLGT on HFD-induced obesity.}, }
@article {pmid39592752, year = {2024}, author = {Chatthanathon, P and Leelahavanichkul, A and Cheibchalard, T and Wilantho, A and Hirankarn, N and Somboonna, N}, title = {Author Correction: Comparative time-series analyses of gut microbiome profiles in genetically and chemically induced lupus-prone mice and the impacts of fecal transplantation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {29391}, doi = {10.1038/s41598-024-79960-5}, pmid = {39592752}, issn = {2045-2322}, }
@article {pmid39592644, year = {2024}, author = {Hunthai, S and Usawachintachit, M and Taweevisit, M and Srisa-Art, M and Anegkamol, W and Tosukhowong, P and Rattanachaisit, P and Chuaypen, N and Dissayabutra, T}, title = {Publisher Correction: Unraveling the role of gut microbiota by fecal microbiota transplantation in rat model of kidney stone disease.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {29360}, doi = {10.1038/s41598-024-78864-8}, pmid = {39592644}, issn = {2045-2322}, }
@article {pmid39592438, year = {2024}, author = {Zhang, S and Wen, H and Chen, Y and Ning, J and Hu, D and Dong, Y and Yao, C and Yuan, B and Yang, S}, title = {Crosstalk between gut microbiota and tumor: tumors could cause gut dysbiosis and metabolic imbalance.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.13763}, pmid = {39592438}, issn = {1878-0261}, support = {82303747//National Natural Science Foundation of China/ ; 2020GXLH-Y-010//Key Research and Development Projects of Shaanxi Province/ ; 2022JM-509//Natural Science Basic Research Program of Shaanxi Province/ ; }, abstract = {Gut microbiota has a proven link with the development and treatment of cancer. However, the causality between gut microbiota and cancer development is still unknown and deserves exploration. In this study, we aimed to explore the alterations in gut microbiota in murine tumor models and the crosstalk between the tumor and the gut microbiota. The subcutaneous and intravenous murine tumor models using both the colorectal cancer cell line MC38 and lung cancer cell line LLC were constructed. Then fecal samples before and after tumor inoculation were collected for whole metagenomics sequencing. Both subcutaneous and metastatic tumors markedly elevated the α-diversity of the gut microbiota. Relative abundance of Ligilactobacillus and Lactobacillus was reduced after subcutaneously inoculating tumor cells, whereas Bacteroides and Duncaniella were reduced in metastatic tumors, regardless of tumor type. At the species level, Lachnospiraceae bacterium was enriched after both subcutaneous and intravenous tumors inoculation, whereas levels of Muribaculaceae bacterium Isolate-110 (HZI), Ligilactobacillus murinus and Bacteroides acidifaciens reduced. Metabolic function analysis showed that the reductive pentose phosphate cycle, urea cycle, ketone body biosynthesis, ectoine biosynthesis, C4-dicarboxylic acid cycle, isoleucine biosynthesis, inosine 5'-monophosphate (IMP), and uridine 5'-monophosphate (UMP) biosynthesis were elevated after tumor inoculation, whereas the cofactor and vitamin biosynthesis were deficient. Principal coordinates analysis (PCoA) showed that subcutaneous and metastatic tumors partially shared the same effect patterns on gut microbiota. Furthermore, fecal microbiota transplantation revealed that this altered microbiota could influence tumor growth. Taken together, this study demonstrated that both colorectal cancer (MC38) and non-colorectal cancer (LLC) can cause gut dysbiosis and metabolic imbalance, regardless of tumor type and process of tumor inoculation, and this dysbiosis influenced the tumor growth. This research gives novel insights into the crosstalk between tumors and the gut microbiota.}, }
@article {pmid39591377, year = {2024}, author = {Tafader, A and Bajaj, JS}, title = {Present and future of fecal microbiome transplantation in cirrhosis.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {}, number = {}, pages = {}, doi = {10.1097/LVT.0000000000000542}, pmid = {39591377}, issn = {1527-6473}, abstract = {Over the last few decades, there have been tremendous advances in our understanding of the role of the gut microbiome in cirrhosis and the clinical sequelae that follow. Progressive dysbiosis and immune dysregulation occur in patients with cirrhosis. In fact, alterations in the gut microbiome occur long before a diagnosis of cirrhosis is made. Understandably, our attention has recently been diverted toward potential modulators of the gut microbiome and the gut-liver axis as targets for treatment. The goal of this review is to highlight the utility of manipulating the gut microbiome with a focus on fecal microbiome transplantation (FMT) in patients with cirrhosis. In addition, we will provide an overview of disease-specific microbial alterations and the resultant impact this has on cirrhosis-related complications.}, }
@article {pmid39590350, year = {2024}, author = {Chen, Z and Liao, Y and Chai, S and Yang, Y and Ga, Q and Ge, R and Wang, S and Liu, S}, title = {Modification of Intestinal Flora Can Improve Host Metabolism and Alleviate the Damage Caused by Chronic Hypoxia.}, journal = {Current issues in molecular biology}, volume = {46}, number = {11}, pages = {12733-12745}, pmid = {39590350}, issn = {1467-3045}, support = {[2130122.1779.36]//Qinghai Province Cattle Industry Science and Technology Innovation Platform under Grant/ ; }, abstract = {Prolonged exposure to hypoxic conditions can lead to reduced appetite, stunted growth, systemic inflammation, and pulmonary hypertension. Previous studies have indicated a correlation between gut dysbiosis and the development of hypoxia-related hazards. We designed an experiment to investigate the effect of microbiota on mitigating hypoxic damage. Gut microbiota from high-altitude-adapted species (Ochotona curzoniae) were transplanted into Sprague Dawley (SD) rats, which were then housed in a simulated 6000 m altitude environment for 30 days. After the experiment, we conducted analyses on average daily weight gain (ADG), feed conversion ratio (FCR), mean pulmonary artery pressure (mPAP), gut flora, and fecal metabolism. The results demonstrated that the ADG in the transplantation group (2.98 ± 0.17 g) was significantly higher than in the control groups (2.68 ± 0.19 g and 2.26 ± 0.13 g) (p < 0.05). The FCR was reduced in the transplantation group (6.30 ± 0.33 g) compared to the control groups (8.20 ± 1.15 g and 8.83 ± 0.45 g) (p < 0.05). The mPAP was decreased in the transplantation group (38.1 ± 1.13 mmHg) compared to the control groups (43.4 ± 1.30 mmHg and 43.5 ± 1.22 mmHg) (p < 0.05). Multi-omics analysis revealed that Lachnospiraceae, Desulfovibrionaceae, and specific amino acid metabolic pathways play crucial roles in hypoxia and are associated with both inflammation and nutritional metabolism. This study proposes a novel approach to the treatment of hypoxic pulmonary hypertension and holds potential significance for improving high-altitude developmental potential.}, }
@article {pmid39589553, year = {2025}, author = {Kellogg, TD and Ceglia, S and Mortzfeld, BM and Tanna, TM and Zeamer, AL and Mancini, MR and Foley, SE and Ward, DV and Bhattarai, SK and McCormick, BA and Reboldi, A and Bucci, V}, title = {Succinate-producing microbiota drives tuft cell hyperplasia to protect against Clostridioides difficile.}, journal = {The Journal of experimental medicine}, volume = {222}, number = {1}, pages = {}, pmid = {39589553}, issn = {1540-9538}, support = {//American Association of Immunologists/ ; PRMP W81XWH2020013//Congressionally Directed Medical Research Programs/ ; //Charles A. King Trust/ ; //Kenneth Rainin Foundation/ ; U01AI172987/NH/NIH HHS/United States ; /GATES/Bill &amp; Melinda Gates Foundation/United States ; T32 AI007349/AI/NIAID NIH HHS/United States ; R01 AG075283/AG/NIA NIH HHS/United States ; U01 AI172987/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Clostridioides difficile ; Mice ; *Succinic Acid/metabolism ; *Hyperplasia ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/pharmacology ; Colon/microbiology/pathology/metabolism ; Mice, Knockout ; Cytokines/metabolism ; Tuft Cells ; }, abstract = {The role of microbes and their metabolites in modulating tuft cell (TC) dynamics in the large intestine and the relevance of this pathway to infections is unknown. Here, we uncover that microbiome-driven colonic TC hyperplasia protects against Clostridioides difficile infection. Using selective antibiotics, we demonstrate increased type 2 cytokines and TC hyperplasia in the colon but not in the ileum. We demonstrate the causal role of the microbiome in modulating this phenotype using fecal matter transplantation and administration of consortia of succinate-producing bacteria. Administration of succinate production-deficient microbes shows a reduced response in a Pou2f3-dependent manner despite similar intestinal colonization. Finally, antibiotic-treated mice prophylactically administered with succinate-producing bacteria show increased protection against C. difficile-induced morbidity and mortality. This effect is nullified in Pou2f3-/- mice, confirming that the protection occurs via the TC pathway. We propose that activation of TCs by the microbiota in the colon is a mechanism evolved by the host to counterbalance microbiome-derived cues that facilitate invasion by pathogens.}, }
@article {pmid39589476, year = {2024}, author = {Ma, G and Chen, Z and Li, Z and Xiao, X}, title = {Unveiling the neonatal gut microbiota: exploring the influence of delivery mode on early microbial colonization and intervention strategies.}, journal = {Archives of gynecology and obstetrics}, volume = {310}, number = {6}, pages = {2853-2861}, pmid = {39589476}, issn = {1432-0711}, support = {No. 81771664//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Cesarean Section/adverse effects ; Infant, Newborn ; *Delivery, Obstetric/methods ; Female ; Pregnancy ; *Probiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Breast Feeding ; Prebiotics/administration &amp; dosage ; }, abstract = {Recent research has emphasized the critical importance of establishing the neonatal gut microbiota for overall health and immune system development, prompting deeper studies about the early formation of neonatal gut microbiota and its influencing factors. Various factors, including maternal and environmental factors, affect the early formation of neonatal gut microbiota, in which delivery mode has been considered as one of the most crucial influencing factors. In recent years, the increasing trend of cesarean section during childbirth has become a serious challenge for global public health. This review thoroughly analyzes the effects of vaginal delivery and cesarean section on the establishment of neonatal gut microbiota and the potential long-term impacts. In addition, we analyze and discuss interventions such as probiotics, prebiotics, vaginal seeding, fecal microbiota transplantation, and breastfeeding to address the colonization defects of the neonatal gut microbiota caused by cesarean section, aiming to provide theoretical basis for the prevention and treatment of colonization defects and related diseases in infants caused by cesarean section in clinical practice and to provide a theoretical foundation for optimizing the development of neonatal gut microbiota.}, }
@article {pmid39589434, year = {2024}, author = {Liu, L and Zhu, JW and Wu, JL and Li, MZ and Lu, ML and Yu, Y and Pan, L}, title = {Insomnia and intestinal microbiota: a narrative review.}, journal = {Sleep &amp; breathing = Schlaf &amp; Atmung}, volume = {29}, number = {1}, pages = {10}, pmid = {39589434}, issn = {1522-1709}, support = {No. ZR2021MH360//Natural Science Foundation of Shandong Province/ ; No. 82370092//National Natural Science Foundation of China/ ; No. 2023SHFZ033//Science and Technology Innovation Project of Binzhou Social Development/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Sleep Initiation and Maintenance Disorders/therapy/physiopathology/microbiology ; Fecal Microbiota Transplantation ; Brain-Gut Axis/physiology ; Probiotics/therapeutic use ; }, abstract = {PURPOSE: The intestinal microbiota and insomnia interact through the microbiota-gut-brain axis. The purpose of this review is to summarize and analyze the changes of intestinal microbiota in insomnia, the interaction mechanisms between intestinal microbiota and insomnia and the treatment methods based on the role of microbiota regulation in insomnia, in order to reveal the feasibility of artificial intervention of intestinal microbiota to improve insomnia.<br><br>METHODS: Pubmed/ Embase were searched through March 2024 to explore the relevant studies, which included the gut microbiota characteristics of insomnia patients, the mechanisms of interaction between insomnia and gut microbiota, and the relationship between gut microbiota and insomnia treatment.<br><br>RESULTS: Numerous studies implicated insomnia could induce intestinal microbiota disorder by activating the immune response, the hypothalamic-pituitary-adrenal axis, the neuroendocrine system, and affecting bacterial metabolites, resulting in intestinal ecological imbalance, intestinal barrier destruction and increased permeability. The intestinal microbiota exerted an influence on the central nervous system through its interactions with intestinal neurons, releasing neurotransmitters and inflammatory factors, which in turn, can exacerbate symptoms of insomnia. Artificial interventions of gut microbiota included probiotics, traditional Chinese medicine, fecal microbiota transplantation, diet and exercise, whose main pathway of action is to improve sleep by affecting the release of neurotransmitters and gut microbial metabolites.<br><br>CONCLUSION: There is an interaction between insomnia and gut microbiota, and it is feasible to diagnose and treat insomnia by focusing on changes in the gut microbiota of patients with insomnia. Large cross-sectional studies and fecal transplant microbiota studies are still needed in the future to validate its safety and efficacy.}, }
@article {pmid39588934, year = {2024}, author = {Gil-Gómez, A and Muñoz-Hernández, R and Martínez, F and Jiménez, F and Romero-Gómez, M}, title = {Hepatic encephalopathy: experimental drugs in development and therapeutic potential.}, journal = {Expert opinion on investigational drugs}, volume = {33}, number = {12}, pages = {1219-1230}, doi = {10.1080/13543784.2024.2434053}, pmid = {39588934}, issn = {1744-7658}, mesh = {Humans ; *Hepatic Encephalopathy/drug therapy/physiopathology ; *Drug Development ; Animals ; *Drugs, Investigational/pharmacology/therapeutic use ; Randomized Controlled Trials as Topic ; Fecal Microbiota Transplantation ; Precision Medicine ; Research Design ; }, abstract = {INTRODUCTION: Hepatic encephalopathy (HE) presents a complex pathophysiology, creating multiple potential treatment avenues. This review covers current and emerging treatments for HE.<br><br>AREAS COVERED: Standard therapies, including non-absorbable disaccharides and rifaximin, are widely used but show inconsistent efficacy. Alternatives such as polyethylene glycol and L-ornithine L-aspartate have been effective in certain cases. Advancements in understanding HE reveal a growing need for personalized treatments. Novel approaches targeting immune modulation and neuroinflammation are under investigation, though clinical translation is slow. Nutritional interventions and fecal microbiota transplantation show potential but lack robust evidence. Innovative therapies like gene and cell therapies, as well as extracellular vesicles from mesenchymal stem cells, present promising avenues for liver disease treatment, potentially benefiting HE.<br><br>EXPERT OPINION: A key challenge in HE research is the design of randomized clinical trials, which often suffer from small sample sizes, heterogeneity in patient population, and inconsistent blinding. Additionally, the multifactorial nature of HE, together with a high spontaneous response rate, complicates efforts to isolate treatment effects. Despite current limitations, ongoing research and technological advances hold promise for more effective and individualized HE treatments in the future.}, }
@article {pmid39588716, year = {2024}, author = {Tiwari, A and Ika Krisnawati, D and Susilowati, E and Mutalik, C and Kuo, TR}, title = {Next-Generation Probiotics and Chronic Diseases: A Review of Current Research and Future Directions.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {50}, pages = {27679-27700}, pmid = {39588716}, issn = {1520-5118}, mesh = {*Probiotics ; Humans ; *Gastrointestinal Microbiome ; Chronic Disease/therapy ; Animals ; *Fecal Microbiota Transplantation ; Bacteria/genetics/classification/metabolism ; }, abstract = {The burgeoning field of microbiome research has profoundly reshaped our comprehension of human health, particularly highlighting the potential of probiotics and fecal microbiota transplantation (FMT) as therapeutic interventions. While the benefits of traditional probiotics are well-recognized, the efficacy and mechanisms remain ambiguous, and FMT's long-term effects are still being investigated. Recent advancements in high-throughput sequencing have identified gut microbes with significant health benefits, paving the way for next-generation probiotics (NGPs). These NGPs, engineered through synthetic biology and bioinformatics, are designed to address specific disease states with enhanced stability and viability. This review synthesizes current research on NGP stability, challenges in delivery, and their applications in preventing and treating chronic diseases such as diabetes, obesity, and cardiovascular diseases. We explore the physiological characteristics, safety profiles, and mechanisms of action of various NGP strains while also addressing the challenges and opportunities presented by their integration into clinical practice. The potential of NGPs to revolutionize microbiome-based therapies and improve clinical outcomes is immense, underscoring the need for further research to optimize their efficacy and ensure their safety.}, }
@article {pmid39588509, year = {2024}, author = {Zhang, A and Chen, S and Zhu, Y and Wu, M and Lu, B and Zhou, X and Zhu, Y and Xu, X and Liu, H and Zhu, F and Lin, R}, title = {Intestinal microbiome changes and mechanisms of maintenance hemodialysis patients with constipation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1495364}, pmid = {39588509}, issn = {2235-2988}, mesh = {Humans ; *Constipation/microbiology ; *Gastrointestinal Microbiome ; *Renal Dialysis ; *Feces/microbiology ; Male ; *RNA, Ribosomal, 16S/genetics ; Middle Aged ; Female ; *Bacteria/classification/isolation &amp; purification/genetics ; Aged ; Adult ; }, abstract = {BACKGROUND: Constipation is a common symptom in maintenance hemodialysis patients and greatly affects the quality of survival of hemodialysis patients. Fecal microbiota transplantation and probiotics are feasible treatments for functional constipation, but there is still a gap in the research on the characteristics of gut flora in patients with maintenance hemodialysis combined with constipation. The aim of this study is to clarify the characteristics of the intestinal flora and its changes in maintenance hemodialysis patients with constipation.<br><br>METHODS: Fecal samples were collected from 45 participants, containing 15 in the maintenance hemodialysis constipation group,15 in the maintenance hemodialysis non-constipation group and 15 in the healthy control group. These samples were analyzed using 16S rRNA gene sequencing. The feature of the intestinal microbiome of maintenance hemodialysis constipation group and the microbiome differences among the three groups were elucidated by species annotation analysis, &#x3b1;-diversity analysis, &#x3b2;-diversity analysis, species difference analysis, and predictive functional analysis.<br><br>RESULTS: The alpha diversity analysis indicated that maintenance hemodialysis constipation group was less diverse and homogeneous than maintenance hemodialysis non-constipation group and healthy control group. At the genus level, the top ten dominant genera in maintenance hemodialysis constipation group patients were Enterococcus, Escherichia-Shigella, Bacteroides, Streptococcus, Bifidobacterium, Ruminococcus_gnavus_group, Lachnospiraceae_unclassified, Faecalibacterium, Akkermansia and UCG-002. Compared with non-constipation group, the Enterococcus, Rhizobiales_unclassified, Filomicrobium, Eggerthella, Allobaculum, Prevotella_7, Gordonibacter, Mitochondria_unclassified, Lachnoanaerobaculum were significantly higher in constipation group (p<0.05). Compared with non-constipation group, the Kineothrix, Rhodopirellula, Weissella were significantly lower in constipation group (p<0.05). The predictive functional analysis revealed that compared with non-constipation group, constipation group was significantly enriched in pathways associated with pyruate metabolism, flavonoid biosynthesis.<br><br>CONCLUSIONS: This study describes for the first time the intestinal microbiome characteristics of maintenance hemodialysis patients with constipation. The results of this study suggest that there is a difference in the intestinal flora between maintenance hemodialysis patients with constipation and maintenance hemodialysis patients without constipation.}, }
@article {pmid39588438, year = {2024}, author = {Dandamudi, BJ and Dimaano, KAM and Shah, N and AlQassab, O and Al-Sulaitti, Z and Nelakuditi, B and Mohammed, L}, title = {Neurodegenerative Disorders and the Gut-Microbiome-Brain Axis: A Literature Review.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72427}, pmid = {39588438}, issn = {2168-8184}, abstract = {Neurodegenerative diseases are severe, age-related conditions with complex etiologies that result in significant morbidity and mortality. The gut microbiome, a dynamic symbiotic environment comprising commensal organisms, represents the largest reservoir of these organisms within the human body. It produces short-chain fatty acids, endogenous signals, and neuroactive compounds, which can modulate neuronal function, plasticity, and behavior. Emerging evidence suggests that the gut microbiome plays a pivotal role in neurodevelopment, aging, and brain diseases, including Alzheimer's disease, Parkinson's disease, and stroke. Communication between the gut and brain occurs through a bidirectional channel known as the gut-microbiome-brain axis, which is being explored for therapeutic potential in neurodegenerative disorders. This literature review was conducted through a comprehensive search of five electronic databases - PubMed, Scopus, Ovid Medline, Cochrane Review, and Google Scholar - from inception to June 2024, focusing on English-language studies. Keywords included "gut-brain axis", "microbiome dysbiosis", "neurodegeneration", and disorder-specific terms such as "Alzheimer's disease" and "Parkinson's disease", paired with "gut microbiome". The review examines current knowledge on the relationship between gut microbiota and neurodegenerative disorders, emphasizing potential mechanisms and therapeutic options. Results indicate that gut dysbiosis, characterized by microbial imbalance, is intricately associated with neurodegenerative disease pathogenesis by influencing immune responses, increasing blood-brain barrier permeability, and generating neurotoxic metabolites. Therapeutic approaches targeting the gut microbiome, including probiotics, prebiotics, and fecal microbiota transplantation, show promise in restoring microbial balance and slowing disease progression. However, further research is essential to validate these findings and develop effective clinical interventions.}, }
@article {pmid39587707, year = {2024}, author = {Ilozumba, MN and Lin, T and Hardikar, S and Byrd, DA and Round, JL and Stephens, WZ and Holowatyj, AN and Warby, CA and Damerell, V and Li, CI and Figueiredo, JC and Toriola, AT and Shibata, D and Fillmore, GC and Pickron, B and Siegel, EM and Kahlert, C and Florou, V and Gigic, B and Ose, J and Ulrich, CM}, title = {Fusobacterium nucleatum Abundance is Associated with Cachexia in Colorectal Cancer Patients: The ColoCare Study.}, journal = {Cancer medicine}, volume = {13}, number = {22}, pages = {e70431}, pmid = {39587707}, issn = {2045-7634}, support = {R01 CA207371/CA/NCI NIH HHS/United States ; //the German Ministry of Education and Research project PerMiCCion (01KD2101D)/ ; //German Cancer Research Center/ ; R01 CA254108/CA/NCI NIH HHS/United States ; //Huntsman Cancer Foundation/ ; R01 CA189184/CA/NCI NIH HHS/United States ; R01 AG083580/AG/NIA NIH HHS/United States ; //ERA-NET (European Research Area Network) on Translational Cancer Research (TRANSCAN) project/ ; U01 CA206110/CA/NCI NIH HHS/United States ; //the Rahel-Goitein-Straus-Program, Medical Faculty Heidelberg University/ ; //Stiftung LebensBlicke, Matthias Lackas Stiftung, Claussen-Simon Stiftung/ ; K07 CA222060/CA/NCI NIH HHS/United States ; //the German Consortium of Translational Cancer Research, (DKTK)/ ; R01 CA211705/CA/NCI NIH HHS/United States ; //University of Utah Immunology, Inflammation, and Infectious Disease Initiative/ ; //Cancer Control and Population Health Sciences (CCPS) at the University of Utah/ ; }, mesh = {Humans ; *Colorectal Neoplasms/complications/microbiology ; Male ; *Cachexia/etiology/microbiology ; *Fusobacterium nucleatum/isolation &amp; purification ; Female ; Aged ; Middle Aged ; *Feces/microbiology ; Fusobacterium Infections/complications/microbiology ; Neoplasm Staging ; Risk Factors ; }, abstract = {BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and indicates poor prognosis. The impact of Fusobacterium nucleatum (Fn), a microbial risk factor for colorectal cancer (CRC), on the development of cachexia in CRC has not been established.<br><br>METHODS: We evaluated the association between Fn abundance in pre-surgical stool samples and onset of cachexia at 6&#x2009;months post-surgery in n&#x2009;=&#x2009;87 patients with stages I-III CRC in the ColoCare Study.<br><br>RESULTS: High fecal Fn abundance compared to negative/low fecal Fn abundance was associated with 4-fold increased risk of cachexia onset at 6&#x2009;months post-surgery (OR&#x2009;=&#x2009;4.82, 95% CI&#x2009;=&#x2009;1.15, 20.10, p&#x2009;=&#x2009;0.03).<br><br>CONCLUSION: Our findings suggest that high fecal Fn abundance was associated with an increased risk of cachexia at 6&#x2009;months post-surgery in CRC patients. This is the first study to link Fn abundance with cachexia in CRC patients, offering novel insights into biological mechanisms and potential management of cancer cachexia. Due to the small sample size, our results should be interpreted with caution. Future studies with larger sample sizes are needed to validate these findings.}, }
@article {pmid39587339, year = {2024}, author = {Castells-Nobau, A and Puig, I and Motger-Albertí, A and de la Vega-Correa, L and Rosell-Díaz, M and Arnoriaga-Rodríguez, M and Escrichs, A and Garre-Olmo, J and Puig, J and Ramos, R and Ramió-Torrentà, L and Pérez-Brocal, V and Moya, A and Pamplona, R and Jové, M and Sol, J and Martin-Garcia, E and Martinez-Garcia, M and Deco, G and Maldonado, R and Fernández-Real, JM and Mayneris-Perxachs, J}, title = {Microviridae bacteriophages influence behavioural hallmarks of food addiction via tryptophan and tyrosine signalling pathways.}, journal = {Nature metabolism}, volume = {6}, number = {11}, pages = {2157-2186}, pmid = {39587339}, issn = {2522-5812}, support = {PI15/01934//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; CD20/00051//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; RD16/0017/0020//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; PI20/01090//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; CP18/00009//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; PI23/00575//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; SLT017_20_000164//Generalitat de Catalunya (Government of Catalonia)/ ; 2021SGR00990//Generalitat de Catalunya (Government of Catalonia)/ ; 2017 SGR-669//Generalitat de Catalunya (Government of Catalonia)/ ; SLT002/16/00250//Government of Catalonia | Departament de Salut, Generalitat de Catalunya/ ; LCF/PR/HR22/52420017//"la Caixa" Foundation (Caixa Foundation)/ ; PNSD- 2019I006//Ministerio de Sanidad, Servicios Sociales e Igualdad (Ministry of Health, Social Services and Equality)/ ; PNSD- 2021I076//Ministerio de Sanidad, Servicios Sociales e Igualdad (Ministry of Health, Social Services and Equality)/ ; }, mesh = {*Tryptophan/metabolism ; Animals ; Mice ; Humans ; *Bacteriophages/physiology ; *Signal Transduction ; *Gastrointestinal Microbiome ; *Tyrosine/metabolism ; *Food Addiction ; Male ; Female ; }, abstract = {Food addiction contributes to the obesity pandemic, but the connection between how the gut microbiome is linked to food addiction remains largely unclear. Here we show that Microviridae bacteriophages, particularly Gokushovirus WZ-2015a, are associated with food addiction and obesity across multiple human cohorts. Further analyses reveal that food addiction and Gokushovirus are linked to serotonin and dopamine metabolism. Mice receiving faecal microbiota and viral transplantation from human donors with the highest Gokushovirus load exhibit increased food addiction along with changes in tryptophan, serotonin and dopamine metabolism in different regions of the brain, together with alterations in dopamine receptors. Mechanistically, targeted tryptophan analysis shows lower anthranilic acid (AA) concentrations associated with Gokushovirus. AA supplementation in mice decreases food addiction and alters pathways related to the cycle of neurotransmitter synthesis release. In Drosophila, AA regulates feeding behaviour and addiction-like ethanol preference. In summary, this study proposes that bacteriophages in the gut microbiome contribute to regulating food addiction by modulating tryptophan and tyrosine metabolism.}, }
@article {pmid39586550, year = {2025}, author = {Novelle, MG and Naranjo-Martínez, B and López-Cánovas, JL and Díaz-Ruiz, A}, title = {Fecal microbiota transplantation, a tool to transfer healthy longevity.}, journal = {Ageing research reviews}, volume = {103}, number = {}, pages = {102585}, doi = {10.1016/j.arr.2024.102585}, pmid = {39586550}, issn = {1872-9649}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Longevity ; *Gastrointestinal Microbiome/physiology ; Aging/physiology ; Animals ; }, abstract = {The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. This review explores how preconditioning donors via standard - lifestyle and pharmacological - antiaging interventions reshape gut microbiome, with the resulting benefits being also FMT-transferable. Finally, we expose the current clinical uses of FMT in the context of aging therapy and address FMT challenges - regulatory landscape, protocol standardization, and health risks - that require refinement to effectively utilize microbiome interventions in the elderly.}, }
@article {pmid39586125, year = {2025}, author = {Ye, H and Wang, H and Han, B and Chen, K and Wang, X and Ma, F and Cheng, L and Zheng, S and Zhao, X and Zhu, J and Li, J and Hong, M}, title = {Guizhi Shaoyao Zhimu decoction inhibits neutrophil extracellular traps formation to relieve rheumatoid arthritis via gut microbial outer membrane vesicles.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {136}, number = {}, pages = {156254}, doi = {10.1016/j.phymed.2024.156254}, pmid = {39586125}, issn = {1618-095X}, mesh = {Animals ; *Extracellular Traps/drug effects ; *Arthritis, Rheumatoid/drug therapy/microbiology ; *Drugs, Chinese Herbal/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Arthritis, Experimental/drug therapy ; Male ; Fecal Microbiota Transplantation ; Mice, Inbred DBA ; Neutrophils/drug effects ; }, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with a high disability rate. Accumulating studies suggest that neutrophil extracellular traps (NETs) play a crucial role in the pathogenesis of RA and targeting NETs has emerged as a potential therapeutic strategy for RA. As a traditional Chinese medicine, Guizhi-Shaoyao-Zhimu Decoction (GSZD) has exhibited good efficacy in the treatment of rheumatoid arthritis (RA), while the underly mechanism especially the possibility that GSZD alter NETs formation to relieve RA remains unknown.<br><br>PURPOSE: Our study aimed to investigate relationship between GSZD and NETs in RA treatment and revealed underlying mechanism.<br><br>METHODS: We constructed collagen-induced arthritis (CIA) model and treated CIA mice with GZSY to validate therapeutic effects of GSZD and examine whether GZSD could inhibit NETs formation in RA. And 16S rRNA sequencing and Fecal microbiota transplantation (FMT) experiment were performed to determine whether GSZD could reduce NETs formation to alleviate RA in gut microbiota-associated manner and identify crucial bacterium in response to GSZD administration. CIA mice treated with effective bacteria and its outer membrane vesicles (OMVs) with oral administration to investigate protective effect against RA and NETs regulative efficiency. We utilized small interfering RNA in vivo and vitro to silence gene mediating effect of GZSD-gut microbiota-NETs.<br><br>RESULTS: GSZD could inhibit NETs formation and relive arthritis in CIA mice. Additionally, GSZD alter gut microbiota composition and significantly increase intestinal Parabacteroides goldsteinii (P.goldsteinii) abundance. Mechanistically, P.goldsteinii enriched by GSZD secreted outer membrane vesicles (OMVs) to translocate into joints and activate Cav-1-Nrf2 axis, leading to reduced NETs formation and alleviate arthritis. In clinical, the abundance of P.goldsteinii exhibited negative correlation with NETs indexes and RA disease activities.<br><br>CONCLUSION: Our findings suggest that GSZD inhibits NETs formation to relieve RA in P.goldsteinii-Cav-1-Nrf2 associated manner, which could provide new sight of the prevention and treatment of RA.}, }
@article {pmid39583974, year = {2024}, author = {Naito, Y and Takagi, T}, title = {Role of gut microbiota in inflammatory bowel disease pathogenesis.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {75}, number = {3}, pages = {175-177}, pmid = {39583974}, issn = {0912-0009}, abstract = {The role of the gut microbiota, especially bacterial flora, in the pathogenesis of inflammatory bowel disease (IBD) is becoming clearer. Advances in gut microbiota analysis and the use of gnotobiotics models have underscored the importance of gut bacteria and their metabolites in the progression of IBD. Fecal microbiota transplantation has shown promise in clinical trials for ulcerative colitis started as Advanced Medical Care B in Japan, raising expectations for its outcomes. This review explores the gut microbiota's role in IBD, encompassing both current knowledge and future prospects.}, }
@article {pmid39582897, year = {2024}, author = {Wang, Z and Wu, X and Wang, Y and Wen, Q and Cui, B and Zhang, F}, title = {Colonic transendoscopic enteral tubing is revolutionizing intestinal therapeutics, diagnosis, and microbiome research.}, journal = {Therapeutic advances in gastroenterology}, volume = {17}, number = {}, pages = {17562848241301574}, pmid = {39582897}, issn = {1756-283X}, abstract = {The intestine, as a crucial organ of the human body, has remained enigmatic despite the remarkable advancements in modern medical technology. Over the past decades, the invention of endoscopic technology has made the noninvasive intervention of the intestine a reality, expanding diagnostic and therapeutic options for diseases. However, due to the single-treatment feature of endoscopic procedures, continuous or repeated medication administration, sampling, and decompression drainage within the intestine have yet to be fulfilled. These limitations persisted until the invention of colonic transendoscopic enteral tubing (TET) in 2014, which realized repeated fecal microbiota transplantation, medication administration, and decompression drainage for the treatment of colon perforation and intestinal obstruction, as well as in situ dynamic sampling. These breakthroughs have not gone unnoticed, gaining global attention and recommendations from guidelines and consensuses. TET has emerged as a novel microbial research tool that offers new paradigms for human microbiome research. This review aims to update the research progress based on TET.}, }
@article {pmid39581510, year = {2025}, author = {Zhang, X and Klöhn, M and Ouwerkerk-Mahadevan, S and Jagst, M and Vereyken, L and Verboven, P and Goovaerts, Q and Todt, D and Jonckers, THM and Coelmont, L and Fletcher, H and Das, K and Samby, K and Neyts, J and Steinmann, E and Koul, A and Kaptein, SJF}, title = {A Pangenotypic Hepatitis E Virus Replication Inhibitor With High Potency in a Rat Infection Model.}, journal = {Gastroenterology}, volume = {168}, number = {4}, pages = {769-783.e12}, doi = {10.1053/j.gastro.2024.10.043}, pmid = {39581510}, issn = {1528-0012}, mesh = {Animals ; *Antiviral Agents/pharmacology/pharmacokinetics/therapeutic use ; *Hepatitis E virus/drug effects/genetics/physiology ; *Hepatitis E/drug therapy/virology ; Humans ; *Virus Replication/drug effects ; Disease Models, Animal ; Rats, Nude ; Rats ; Hepatocytes/virology/drug effects ; Female ; RNA, Viral ; Male ; Replicon ; }, abstract = {BACKGROUND &amp; AIMS: Hepatitis E virus (HEV) constitutes a substantial public health burden with ∼20 million human infections annually, including 3.3 million symptomatic cases. Appropriate treatment options for, in particular, HEV-infected immunocompromised patients and pregnant women are lacking, underscoring the urgent need for potent and safe antiviral drugs.<br><br>METHODS: HEV subgenomic replicon systems were used to screen a small library of preselected nucleoside analogues, originally developed in a hepatitis C virus (HCV) antiviral program. Antiviral activity of the selected hit on HEV infection was evaluated in a variety of cell culture systems, and the efficacy of the compound was assessed in the athymic nude rat HEV infection model.<br><br>RESULTS: Compound JNJ-9117 exerts pangenotype antiviral activity against HEV in different cell types as well as in primary human hepatocytes. A high level of conservation is observed between 3 crucial motifs in the catalytic domain of the HCV and HEV polymerases. This suggests a mechanism of action that is identical to that of the molecule against HCV, whereby the 5'-triphosphate of JNJ-9117 acts as a chain terminator during viral RNA synthesis. JNJ-9117 has a favorable pharmacokinetic and safety profile in rats and results in a pronounced antiviral effect in a chronic rat HEV infection model, both in a prophylactic and therapeutic setting. The combination of JNJ-9117 and ribavirin (each at an intentionally selected suboptimal/inactive dose) was highly effective in infected rats in lowering the viral RNA load in liver and feces to (almost) undetectable levels.<br><br>CONCLUSIONS: JNJ-9117 has a profile that holds promise for the treatment of life-threatening HEV infections in humans. Phase I studies with JNJ-9117 have been initiated in healthy human volunteers.}, }
@article {pmid39580105, year = {2025}, author = {Fülöpová, N and Brückner, K and Muselík, J and Pavloková, S and Franc, A}, title = {Development and evaluation of innovative enteric-coated capsules for colon-specific delivery of hydrophilic biomaterials.}, journal = {International journal of pharmaceutics}, volume = {668}, number = {}, pages = {124991}, doi = {10.1016/j.ijpharm.2024.124991}, pmid = {39580105}, issn = {1873-3476}, mesh = {*Capsules ; *Colon/metabolism ; *Hydrophobic and Hydrophilic Interactions ; *Cellulose/chemistry/analogs &amp; derivatives ; *Drug Delivery Systems/methods ; *Gelatin/chemistry ; *Drug Liberation ; Caffeine/chemistry/administration &amp; dosage ; Polymethacrylic Acids/chemistry ; Ferric Compounds/chemistry/administration &amp; dosage ; Polysaccharides, Bacterial/chemistry ; Delayed-Action Preparations/chemistry ; Biocompatible Materials/chemistry ; Hydrogels/chemistry ; Polymers/chemistry ; Polyvinyls/chemistry ; Hypromellose Derivatives/chemistry ; }, abstract = {OBJECTIVE: This research aims to design and evaluate an enteric-coated hard capsule dosage form for targeted delivery of biological materials, such as FMT (fecal microbiota transplant) or live microbes, to the distal parts of the GIT. The capsules are designed to be internally protected against destruction by hydrophilic filling during passage through the digestive tract.<br><br>METHODS: Hard gelatin capsules and DRcaps[TM]capsules based on HPMC and gellan were used to encapsulate a hydrophilic body temperature-liquefying gelatin hydrogel with caffeine or insoluble iron oxide mixture. Different combinations of polymers were tested for the internal (ethylcellulose, Eudragit&#xae; E, and polyvinyl acetate) and external (Eudragit&#xae; S, Acryl-EZE&#xae;, and cellacefate) coating. The external protects against the acidic gastric environment, while the internal protects against the liquid hydrophilic filling during passage. Coated capsules were evaluated using standard disintegration and modified dissolution methods for delayed-release dosage forms.<br><br>RESULTS: Combining suitable internal (ethylcellulose 1.0&#xa0;%) and external (Eudragit&#xae; S 20.0&#xa0;%) coating of DRcaps[TM] capsules with the wiping and immersion method achieved colonic release times. While most coated capsules met the pharmaceutical requirements for delayed release, one combination stood out. Colonic times were indicated by the dissolution of soluble caffeine (during 120-720&#xa0;min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480&#xa0;min) measured by the disintegration method. This promising result demonstrates the composition's suitability and potential to protect the content until it's released, inspiring hope for the future of colon-targeted delivery systems and its potential for the pharmaceutical and biomedical fields.<br><br>CONCLUSION: Innovative and easy capsule coatings offer significant potential for targeted drugs, especially FMT water suspension, to the GIT, preferably the colon. The administration method is robust and not considerably affected by the quantity of internal or external coatings. It can be performed in regular laboratories without specialized individual and personalized treatment equipment, making it a practical and feasible method for drug delivery.}, }
@article {pmid39579562, year = {2024}, author = {Yang, Y and Wu, R and Qian, C and Wu, D and Ou, J}, title = {Mume fructus alters the abundance of intestinal microbiota and alleviates damaged intestinal barrier and inflammation in rats with DSS induced colitis.}, journal = {Molecular immunology}, volume = {176}, number = {}, pages = {60-72}, doi = {10.1016/j.molimm.2024.11.008}, pmid = {39579562}, issn = {1872-9142}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis/microbiology/chemically induced/immunology ; Rats ; *Dextran Sulfate/toxicity ; Male ; *Inflammation ; *Intestinal Mucosa/drug effects/microbiology/immunology ; Drugs, Chinese Herbal/pharmacology ; Rats, Sprague-Dawley ; RNA, Ribosomal, 16S/genetics ; Colon/drug effects/microbiology/pathology ; }, abstract = {The gut microbiota plays a crucial role in the development of colitis by influencing the immune response and inflammation in the colon. Previous research has shown that Mume Fructus, a traditional Chinese medicine, can alleviate colitis by reducing the activity of inflammatory pathways. However, the specific connection between Mume Fructus-treated colitis and regulation of gut flora remains unclear, prompting further investigation. This research aims to delve deeper into the possible impact of the gut microbiota in colitis when treated with the aqueous decoction of Mume Fructus (MF). The effects of MF on rats with DSS-induced colitis were assessed through examination of pathological indicators, intestinal barrier proteins, and analysis of 16S rDNA sequencing to investigate its impact on the gut microbiota. In addition, the colon contents of rats after the administration of MF were transplanted into rats with colitis, and the effect of MF on intestinal flora was verified, and "beneficial bacteria" were identified by 16S rDNA sequencing and Spearman's correlation analysis. In summary, our findings suggest that MF has the potential to ameliorate symptoms of colitis through modulation of intestinal microbiota and restoration of intestinal barrier function.}, }
@article {pmid39574673, year = {2024}, author = {Wolfe, TM and Jo, J and Pinkham, NV and Garey, KW and Walk, ST}, title = {Microbiome impact of ibezapolstat and other Clostridioides difficile infection relevant antibiotics using humanized mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.06.622322}, pmid = {39574673}, issn = {2692-8205}, abstract = {BACKGROUND: Ibezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for treatment of Clostridioides difficile infection (CDI). Previous studies demonstrated IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done. The purpose of this study was to compare microbiome changes associated with IBZ to other clinically used CDI antibiotics.<br><br>METHODS: Groups of germ-free (GF) mice received a fecal microbiota transplant from one of two healthy human donors and were subsequently exposed to either IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control). 16S rRNA encoding gene sequencing of temporally collected stool samples was used to compare gut microbiome perturbation between treatment and no-drug control groups.<br><br>RESULTS: Among the tested antibiotics, the most significant change in microbiome diversity was observed in MET-treated mice. Each antibiotic had a unique effect, but changes in alpha and beta diversity following FDX- and IBZ-treated groups were less pronounced compared to those observed in VAN-or MET-treated groups. By the end of therapy, both IBZ and FDZ increased the relative abundance of Bacteroidota (phylum), with IBZ additionally increasing the relative abundance of Actinomycetota (phylum).<br><br>CONCLUSION: In microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity compared to VAN and MET. Notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies.}, }
@article {pmid39574251, year = {2024}, author = {Shen, CL and Deshmukh, H and Santos, JM and Elmassry, MM and Presto, P and Driver, Z and Bhakta, V and Yakhnitsa, V and Kiritoshi, T and Ji, G and Lovett, J and Hamood, A and Neugebauer, V}, title = {Fecal Microbiota Transplantation Modulates Gut Microbiome Composition and Glial Signaling in Brain and Colon of Rats with Neuropathic Pain: Evidence for Microbiota-Gut-Brain Axis.}, journal = {The Journal of frailty &amp; aging}, volume = {13}, number = {4}, pages = {319-330}, doi = {10.14283/jfa.2024.65}, pmid = {39574251}, issn = {2260-1341}, support = {R01 NS038261/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Neuralgia/therapy/microbiology/metabolism ; Rats ; Male ; *Brain-Gut Axis/physiology ; Neuroglia/metabolism ; Colon/microbiology ; Brain/metabolism ; Rats, Sprague-Dawley ; Disease Models, Animal ; Signal Transduction ; }, abstract = {Despite evidence linking the gut microbiome to neuropathic pain (NP), it is not known if altering gut microbiota can alleviate NP via the microbiome-gut-brain axis. This study examined if healthy gut microbiota of sham male rats (Sham+V) and dysbiotic gut microbiota of NP rats (spinal nerve ligation: NP, SNL+V) can be disrupted and restored, respectively, via fecal microbiota transplant (FMT) from the opposite group [Sham+(SNL-FMT) and SNL+(Sham-FMT), respectively]. All groups received FMT daily for two weeks, followed by three weeks without FMT. SNL rats showed higher mechanical hypersensitivity [SNL+V vs. Sham+V] throughout the study. After two weeks, the FMT of healthy gut microbiota decreased mechanical hypersensitivity in SNL rats [SNL+(Sham-FMT) vs. SNL+V]. A temporal shift in microbiome profiles after 2-week FMT treatment was observed in Sham+(SNL-FMT) and SNL+(Sham-FMT) groups, while the microbiome profile shifted back a certain extent after FMT ceased. At the end of study, the Sham+(SNL-FMT) group acquired low abundance of UCG-001, Odoribacter, and Peptococcaceae, and high abundance of UBA1819 and Victivallis. The SNL+(Sham-FMT) group maintained high abundance of Butyricimonas and Escherichia-Shigella. The SNL+(Sham-FMT) group had altered glial and macrophage activation/inflammation markers in the brain/colon than the SNL+V group. Relative to the SNL+V group, the SNL+(Sham-FMT) group had significantly lower gene expressions of GFAP (hypothalamus), IBA-1 (colon), and NF-κB (amygdala/colon), but higher gene expressions of complex I (amygdala/hypothalamus) and claudin-3 (amygdala/hypothalamus/colon). In conclusion, FMT containing healthy microbiota given to SNL rats attenuates mechanical hypersensitivity, modulates microbiota composition, and mitigates downstream glial activation/inflammation markers in a NP model.}, }
@article {pmid39571844, year = {2024}, author = {Yu, L and Lin, F and Yu, Y and Deng, X and Shi, X and Lu, X and Lu, Y and Wang, D}, title = {Rehmannia glutinosa polysaccharides enhance intestinal immunity of mice through regulating the microbiota.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 3}, pages = {137878}, doi = {10.1016/j.ijbiomac.2024.137878}, pmid = {39571844}, issn = {1879-0003}, mesh = {Animals ; *Polysaccharides/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Rehmannia/chemistry ; Mice ; Fecal Microbiota Transplantation ; Male ; Intestines/immunology/microbiology/drug effects ; Intestinal Mucosa/immunology/drug effects/microbiology ; T-Lymphocytes/immunology/drug effects ; }, abstract = {The Rehmannia glutinosa polysaccharides (RGP) have various benefits such as enhancing immune cell activity, decreasing oxidative stress and delaying or inhibiting tumor occurrence. Although much research has been directed at understanding the role of RGP, its influence on gut immunity is largely understudied. Here, we aimed to dissect the immune-regulating effects of RGP in the mice intestines. In vivo experiments involving the oral administration of RGP to mice at dosages of 100, 200, and 400 mg/kg over seven consecutive days revealed that RGP therapy significantly increased the percentages of CD3[+] T lymphocytes and CD19[+] B lymphocytes in intestines and improved the integrity of the mucosal barrier. Moreover, RGP modified the gut microbiota composition by enhancing the abundance of beneficial bacteria like Lactobacillus and Akkermansia. Fecal microbiota transplantation (FMT) experiments further revealed that RGP modulated the host's intestinal immunological function by altering the gut microbiota composition. These findings indicate that RGP may control the immunological function of the intestines.}, }
@article {pmid39571733, year = {2024}, author = {Yu, J and Feng, L and Luo, Z and Yang, J and Zhang, Q and Liu, C and Liang, D and Xie, Y and Li, H and Gong, J and He, Z and Lan, P}, title = {Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.11.024}, pmid = {39571733}, issn = {2090-1224}, abstract = {INTRODUCTION: The intricate interplay of interleukin-10 (IL-10) and gut microbiota influences tumor development and progression, yet the impacts on colorectal cancer (CRC) metastasis remain incompletely understood.<br><br>METHODS: The impact of Il10 deficiency on CRC metastasis was first evaluated in CRC metastasis tumor samples and mouse model. Antibiotic sterilization and fecal microbiota transplantation (FMT) experiment were used to assess the role of gut microbiota in IL-10 mediated CRC metastasis, and full-length 16S rDNA sequencing analysis further identified the potential target bacteria influencing CRC metastasis. The inhibitory effect of Parabacteroides distasonis (P. distasonis) on CRC metastasis was evaluated by oral administration in mice. Key metabolites involved in P. distasonis inhibition of CRC metastasis was identified by widely-targeted metabolome analysis and validated both in vivo and in vitro. The underlying mechanisms of P-hydroxyphenyl acetic acid (4-HPAA) inhibiting CRC metastasis was investigated via RNA-sequencing and validated in cellular experiments.<br><br>RESULTS: We revealed that serum IL-10 levels were markedly elevated in metastatic CRC patients compared to non-metastatic cases. In parallel, Il10-deficiency (Il10[-/-]) in mice resulted in decreased CRC metastasis in a gut microbiota-dependent manner. Mechanistically, Il10[-/-] mice reshaped gut microbiota composition, notably enriching P. distasonis. The enriched P. distasonis produced 4-HPAA, which activated the aryl hydrocarbon receptor (AHR) and subsequently inhibited the expression of VEGFA, a typical oncogene, thereby sequentially suppressing CRC metastasis. Importantly, engineered bacteria capable of producing 4-HPAA effectively hindered CRC metastasis. Furthermore, AHR depletion significantly disrupted the 4-HPAA-induced reduction in CRC cell migration and the inhibition of metastasis in both in vitro and in vivo lung metastasis mouse models.<br><br>CONCLUSIONS: These findings demonstrate the significance of IL-10 deficiency in suppressing CRC metastasis through the 4-HPPA-AHR-VEGFA axis mediated by gut P. distasonis, suggesting that P. distasonis or 4-HPAA supplementation could offer a promising therapeutic strategy for CRC metastasis prevention.}, }
@article {pmid39571265, year = {2025}, author = {Mansouri, P and Mansouri, P and Behmard, E and Najafipour, S and Kouhpayeh, A and Farjadfar, A}, title = {Novel targets for mucosal healing in inflammatory bowel disease therapy.}, journal = {International immunopharmacology}, volume = {144}, number = {}, pages = {113544}, doi = {10.1016/j.intimp.2024.113544}, pmid = {39571265}, issn = {1878-1705}, mesh = {Humans ; *Inflammatory Bowel Diseases/drug therapy/therapy/immunology ; *Intestinal Mucosa/immunology/drug effects/pathology/metabolism ; Animals ; Fecal Microbiota Transplantation ; Anti-Inflammatory Agents/therapeutic use/pharmacology ; Wound Healing/drug effects ; Molecular Targeted Therapy ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic condition affecting the gastrointestinal tract, primarily manifesting as ulcerative colitis (UC) or Crohn's disease (CD). Both inflammation and disruption of the intestinal epithelial barrier are key factors in IBD pathogenesis. Substantial evidence has revealed a significant association between aberrant immune responses and impairment of the intestinal epithelial barrier in IBD pathogenesis. The components of the intestinal epithelium, particularly goblet cells and Paneth cells, are crucial to gut homeostasis, as they secrete mucin, antimicrobial peptides (AMPs), and cytokines. Furthermore, impairment of epithelial integrity, which is regulated by tight junctions, is a hallmark of IBD pathology. While common treatments for IBD, such as anti-inflammatory drugs, target various signaling pathways with varying efficacies, therapeutic approaches focused on mucosal and epithelial barrier healing have been largely neglected. Moreover, high costs, side effects, and insufficient or inconsistent therapeutic outcomes remain major drawbacks of conventional anti-IBD drugs. Recent studies on epithelial barrier regeneration and permeability reduction have introduced promising therapeutic targets, including farnesoid X receptor (FXR), urokinase-type plasminogen activator (uPA)-urokinase-type plasminogen activator receptor (uPAR) interaction, fecal microbiota transplantation (FMT), and insulin receptor (INSR). Notably, the simultaneous targeting of intestinal inflammation and promotion of epithelial barrier healing shows promise for efficient IBD treatment. Future research should explore targeted therapies and combination treatments, including natural remedies, microbiota colonization, stem cell approaches, and computer-aided drug design. It is also crucial to focus on accurate prognosis and developing a thorough understanding of IBD development mechanisms.}, }
@article {pmid39570086, year = {2024}, author = {Justice, J and Kankaria, RA and Johnson, DB}, title = {Immune checkpoint inhibition of metastatic melanoma: achieving high efficacy in the face of high toxicity.}, journal = {Expert review of clinical pharmacology}, volume = {17}, number = {12}, pages = {1115-1125}, doi = {10.1080/17512433.2024.2431513}, pmid = {39570086}, issn = {1751-2441}, mesh = {Humans ; *Melanoma/drug therapy/pathology/immunology ; *Immune Checkpoint Inhibitors/adverse effects/administration &amp; dosage/pharmacology ; Neoplasm Metastasis ; Animals ; Fecal Microbiota Transplantation/methods ; *Skin Neoplasms/pathology/drug therapy/immunology ; Adrenal Cortex Hormones/administration &amp; dosage ; }, abstract = {INTRODUCTION: Immune checkpoint inhibitors (ICIs) have advanced the treatment of metastatic melanoma by blocking immune system down-regulators enhancing T-cell-mediated anti-tumor responses. However, many ICIs induce immune-related adverse effects (irAEs) that can impact many organ systems.<br><br>AREAS COVERED: Strategies used to manage irAEs include corticosteroids, anti-tumor necrosis factor alpha (TNF-&#x3b1;) agents, other biological therapies, fecal microbiota transplantation (FMT), and emerging regimens. In this review, we describe current evidence for the efficacy of ICIs, acute and chronic immune toxicities, and strategies to manage toxicities for patients treated with ICIs.<br><br>EXPERT OPINION: IrAE management will likely evolve by developing more tailored approaches to prevent toxicities, improving non-steroidal management strategies and tailoring the dose of steroids, and identifying biomarkers of severe toxicities.}, }
@article {pmid39569890, year = {2025}, author = {Jang, S and Yu, J and Park, S and Lim, H and Koh, H and Park, YR}, title = {Development of Time-Aggregated Machine Learning Model for Relapse Prediction in Pediatric Crohn's Disease.}, journal = {Clinical and translational gastroenterology}, volume = {16}, number = {1}, pages = {e00794}, pmid = {39569890}, issn = {2155-384X}, support = {//Ministry of Health and Welfare/ ; }, mesh = {Humans ; *Crohn Disease/diagnosis/blood ; Male ; Retrospective Studies ; Female ; *Machine Learning ; Recurrence ; Child ; Adolescent ; Time Factors ; ROC Curve ; C-Reactive Protein/analysis ; Severity of Illness Index ; Prognosis ; Predictive Value of Tests ; }, abstract = {INTRODUCTION: Pediatric Crohn's disease (CD) easily progresses to an active disease compared with adult CD, making it important to predict and minimize CD relapses. However, prediction of relapse at various time points (TPs) during pediatric CD remains understudied. We aimed to develop a real-time aggregated model to predict pediatric CD relapse in different TPs and time windows (TWs).<br><br>METHODS: This retrospective study was conducted on children diagnosed with CD between 2015 and 2022 at Severance Hospital. Laboratory test results and demographic data were collected starting at 3 months after diagnosis, and cohorts were formed using data from 6 different TPs at 1-month intervals. Relapse-defined as a pediatric CD activity index &#x2265; 30 points-was predicted, and TWs were 3-7 months with 1-month intervals. The feature importance of the variables in each setting was determined.<br><br>RESULTS: Data from 180 patients were used to construct cohorts corresponding to the TPs. We identified the optimal TP and TW to reliably predict pediatric CD relapse with an area under the receiver operating characteristic curve score of 0.89 when predicting with a 3-month TW at a 3-month TP. Variables such as C-reactive protein levels and lymphocyte fraction were found to be important factors.<br><br>DISCUSSION: We developed a time-aggregated model to predict pediatric CD relapse in multiple TPs and TWs. This model identified important variables that predicted relapse in pediatric CD to support real-time clinical decision making.}, }
@article {pmid39568727, year = {2024}, author = {Alam, M and Abbas, K and Mustafa, M and Usmani, N and Habib, S}, title = {Microbiome-based therapies for Parkinson's disease.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1496616}, pmid = {39568727}, issn = {2296-861X}, abstract = {The human gut microbiome dysbiosis plays an important role in the pathogenesis of Parkinson's disease (PD). The bidirectional relationship between the enteric nervous system (ENS) and central nervous system (CNS) under the mediation of the gut-brain axis control the gastrointestinal functioning. This review article discusses key mechanisms by which modifications in the composition and function of the gut microbiota (GM) influence PD progression and motor control loss. Increased intestinal permeability, chronic inflammation, oxidative stress, α-synuclein aggregation, and neurotransmitter imbalances are some key factors that govern gastrointestinal pathology and PD progression. The bacterial taxa of the gut associated with PD development are discussed with emphasis on the enteric nervous system (ENS), as well as the impact of gut bacteria on dopamine production and levodopa metabolism. The pathophysiology and course of the disease are associated with several inflammatory markers, including TNF-α, IL-1β, and IL-6. Emerging therapeutic strategies targeting the gut microbiome include probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). The article explored how dietary changes may affect the gut microbiota (GM) and the ways that can affect Parkinson's disease (PD), with a focus on nutrition-based, Mediterranean, and ketogenic diets. This comprehensive review synthesizes current evidence on the role of the gut microbiome in PD pathogenesis and explores its potential as a therapeutic target. Understanding these complex interactions may assist in the development of novel diagnostic tools and treatment options for this neurodegenerative disorder.}, }
@article {pmid39567117, year = {2025}, author = {Lu, X and Jing, Y and Zhang, N and Chen, L and Tai, J and Cao, Y}, title = {Structural characterization and anti-obesity effect of a novel water-soluble galactomannan isolated from Eurotium cristatum.}, journal = {Carbohydrate polymers}, volume = {348}, number = {Pt B}, pages = {122870}, doi = {10.1016/j.carbpol.2024.122870}, pmid = {39567117}, issn = {1879-1344}, mesh = {Animals ; *Galactose/analogs &amp; derivatives ; *Mannans/chemistry/pharmacology/isolation &amp; purification ; Mice ; *Anti-Obesity Agents/pharmacology/chemistry/isolation &amp; purification ; *Obesity/drug therapy ; Male ; *Diet, High-Fat ; *Eurotium/chemistry ; *Solubility ; Gastrointestinal Microbiome/drug effects ; Water/chemistry ; Mice, Inbred C57BL ; }, abstract = {Obesity is a serious public health challenge worldwide, the present study is aimed to investigate the structural characteristic and anti-obesity effect of a water-soluble galactomannan (PEC) extracted from Eurotium cristatum (E. cristatum). Detailed analysis of the PEC structure showed a weight-average molecular weight of 32,305 Da and a composition of mainly mannose, galactose and small amounts of glucose. Nuclear magnetic resonance spectroscopy combined with methylation analysis indicated that the main chain of PEC is →5)-β-D-Galf-(1 → 6)-α-D-Manp-(1 → glycosidic bond, and the branched chain →2)-α-D-Manp-(1 → through →2,6)-α-D-Manp-(1 → is connected to the main chain by an O-2 bond. Furthermore, PEC was found to ameliorate body weight gain, metabolic disorders, and to modulate the gut microbiota in HFD-fed mice. Fecal microbiota transplantation trial confirmed that PEC prevented obesity development and metabolic disorders by reversing gut dysbiosis in HFD-fed mice. This is the first report of the isolation of PEC from E. cristatum, and the findings suggested that PEC exerted its antiobesity and related beneficial effects by regulating the gut microbiota. In conclusion, as a polysaccharide, PEC could reduce obesity by modulating the gut microbiota and has potential been a prophylactic agent for obesity and related metabolic diseases.}, }
@article {pmid39566790, year = {2024}, author = {Liu, Z and Wang, M and Li, J and Liang, Y and Jiang, K and Hu, Y and Gong, W and Guo, X and Guo, Q and Zhu, B}, title = {Hizikia fusiforme polysaccharides synergized with fecal microbiota transplantation to alleviate gut microbiota dysbiosis and intestinal inflammation.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 4}, pages = {137851}, doi = {10.1016/j.ijbiomac.2024.137851}, pmid = {39566790}, issn = {1879-0003}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation ; *Dysbiosis/therapy ; Mice ; *Polysaccharides/pharmacology ; *Dextran Sulfate ; *Mice, Inbred C57BL ; Colitis, Ulcerative/therapy/microbiology ; Male ; Disease Models, Animal ; Inflammation/therapy/drug therapy ; Edible Seaweeds ; Sargassum ; }, abstract = {Ulcerative colitis (UC) is closely associated with disruptions in gut microbiota. Restoring balance to gut microbiota and reducing intestinal inflammation has become a promising therapeutic approach for UC. However, challenges remain, including limited efficacy in some treatments. This study explores the synergistic effects and underlying mechanisms of Hizikia fusiforme polysaccharides (HFP) combined with fecal microbiota transplantation (FMT) to improve UC symptoms. Seven-week-old C57/BL6J mice were induced with UC using dextran sodium sulfate (DSS). Supplementation with either FMT alone or in combination with HFP effectively alleviated UC symptoms, reduced colonic inflammation, and corrected gut microbiota imbalance. Notably, HFP combined with FMT yielded showed better effects in ameliorating DSS-induced UC in mice than did FMT alone. Enrichment of probiotics, such as Bifidobacterium, and upregulation of beneficial metabolites, such as betaine, were identified as potential mechanisms for the enhanced effects of HFP combined with FMT against DSS-induced UC. These findings suggest that the combination of Hizikia fusiforme polysaccharides with FMT has potential applications in rectifying dysbiosis and ameliorating inflammatory bowel diseases.}, }
@article {pmid39564459, year = {2024}, author = {Zhao, J and Liu, J and Feng, J and Liu, X and Hu, Q}, title = {The gut microbiota-brain connection: insights into major depressive disorder and bipolar disorder.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1421490}, pmid = {39564459}, issn = {1664-0640}, abstract = {Major depressive disorder (MDD) and bipolar disorder (BD) are two of the most prevalent mood disorders that seriously jeopardize both physical and mental health. The current diagnosis of MDD and BD relies primarily on clinical symptoms. However, correctly differentiating between MDD and BD during depressive episode states remains a substantial clinical challenge. The human gut hosts a large and diverse microbiota, which plays a pivotal role in various physiological processes. Emerging evidence suggests that the gut microbiota (GM) exerts beneficial effects on mental health disorders, including MDD, BD, and schizophrenia, through the microbe-gut-brain axis (MGBA). In recent years, the relationship between GM and mood disorders has garnered considerable attention, leading to intensive research in this area. The MGBA is a bidirectional communication system between the gut and the brain. Growing evidence indicates that the brain can influence the GM, which in turn may modulate the brain through this axis. This review aims to explore the changes in the GM of patients with MDD and BD and evaluate the effects of different treatments on their GM, including medication, probiotic, prebiotic and synbiotic interventions, and fecal microbiota transplantation (FMT). By doing so, we seek to identify potential disease-specific biomarkers, improve differential diagnosis, and offer novel therapeutic avenues for these disorders.}, }
@article {pmid39562050, year = {2025}, author = {Li, N and Li, Y and Huang, Z and Cao, Z and Cao, C and Gao, X and Zuo, T}, title = {Faecal phageome transplantation alleviates intermittent intestinal inflammation in IBD and the timing of transplantation matters: a preclinical proof-of-concept study in mice.}, journal = {Gut}, volume = {74}, number = {5}, pages = {868-870}, doi = {10.1136/gutjnl-2024-333598}, pmid = {39562050}, issn = {1468-3288}, }
@article {pmid39557804, year = {2024}, author = {Lee, JY and Kim, Y and Kim, J and Kim, JK}, title = {Fecal Microbiota Transplantation: Indications, Methods, and Challenges.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {62}, number = {12}, pages = {1057-1074}, pmid = {39557804}, issn = {1976-3794}, support = {RS-2024-00340833//National Research Foundation of Korea/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; *Clostridium Infections/therapy/microbiology ; *Feces/microbiology ; *Clostridioides difficile ; Dysbiosis/therapy/microbiology ; Animals ; }, abstract = {Over the past two decades, as the importance of gut microbiota to human health has become widely known, attempts have been made to treat diseases by correcting dysbiosis of gut microbiota through fecal microbiota transplantation (FMT). Apart from current knowledge of gut microbiota, FMT to treat disease has a long history, from the treatment of food poisoning in the fourth century to the treatment of Clostridioides difficile infections in the twentieth century. In 2013, FMT was recognized as a standard treatment for recurrent C. difficile because it consistently showed high efficacy. Though recurrent C. difficile is the only disease internationally recognized for FMT efficacy, FMT has been tested for other diseases and shown some promising preliminary results. Different FMT methods have been developed using various formulations and administration routes. Despite advances in FMT, some issues remain to be resolved, such as donor screening, manufacturing protocols, and unknown components in the fecal microbiota. In this review, we discuss the mechanisms, clinical indications, methods, and challenges of current FMT. We also discuss the development of alternative therapies to overcome the challenges of FMT.}, }
@article {pmid39555931, year = {2025}, author = {Wang, J and Xiang, J-H and Peng, X-Y and Liu, M and Sun, L-J and Zhang, M and Zhang, L-Y and Chen, Z-B and Tang, Z-Q and Cheng, L}, title = {Characteristic alterations of gut microbiota and serum metabolites in patients with chronic tinnitus: a multi-omics analysis.}, journal = {Microbiology spectrum}, volume = {13}, number = {1}, pages = {e0187824}, pmid = {39555931}, issn = {2165-0497}, support = {82071061//MOST | National Natural Science Foundation of China (NSFC)/ ; 32271056//MOST | National Natural Science Foundation of China (NSFC)/ ; JSDW202203//Jiangsu Province Capability Improvement Project through Science, Technology and Education of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Tinnitus/microbiology/blood/metabolism ; Male ; Female ; Middle Aged ; *Feces/microbiology ; *Dysbiosis/microbiology ; Adult ; *Metabolomics/methods ; *Bacteria/classification/genetics/isolation &amp; purification/metabolism ; *RNA, Ribosomal, 16S/genetics ; Chronic Disease ; Metabolome ; Aged ; Multiomics ; }, abstract = {Chronic tinnitus is a central nervous system disorder. Currently, the effects of gut microbiota on tinnitus remain unexplored. To explore the connection between gut microbiota and tinnitus, we conducted 16S rRNA sequencing of fecal microbiota and serum metabolomic analysis in a cohort of 70 patients with tinnitus and 30 healthy volunteers. We used the weighted gene co-expression network method to analyze the relationship between the gut microbiota and the serum metabolites. The random forest technique was utilized to select metabolites and gut taxa to construct predictive models. A pronounced gut dysbiosis in the tinnitus group, characterized by reduced bacterial diversity, an increased Firmicutes/Bacteroidetes ratio, and some opportunistic bacteria including Aeromonas and Acinetobacter were enriched. In contrast, some beneficial gut probiotics decreased, including Lactobacillales and Lactobacillaceae. In serum metabolomic analysis, serum metabolic disturbances in tinnitus patients and these differential metabolites were enriched in pathways of neuroinflammation, neurotransmitter activity, and synaptic function. The predictive models exhibited great diagnostic performance, achieving 0.94 (95% CI: 0.85-0.98) and 0.96 (95% CI: 0.86-0.99) in the test set. Our study suggests that changes in gut microbiota could potentially influence the occurrence and chronicity of tinnitus, and exert regulatory effects through changes in serum metabolites. Overall, this research provides new perceptions into the potential role of gut microbiota and serum metabolite in the pathogenesis of tinnitus, and proposes the "gut-brain-ear" concept as a pathomechanism underlying tinnitus, with significant clinical diagnostic implications and therapeutic potential.IMPORTANCETinnitus affects millions of people worldwide. Severe cases may lead to sleep disorders, anxiety, and depression, subsequently impacting patients' lives and increasing societal healthcare expenditures. However, tinnitus mechanisms are poorly understood, and effective therapeutic interventions are currently lacking. We discovered the gut microbiota and serum metabolomics changes in patients with tinnitus, and provided the potential pathological mechanisms of dysregulated gut flora in chronic tinnitus. We proposed the innovative concept of the "gut-brain-ear axis," which underscores the exploration of gut microbiota impact on susceptibility to chronic tinnitus through serum metabolic profile modulation. We also reveal novel biomarkers associated with chronic tinnitus, offering a new conceptual framework for further investigations into the susceptibility of patients, potential treatment targets for tinnitus, and assessing patient prognosis. Subsequently, gut microbiota and serum metabolites can be used as molecular markers to assess the susceptibility and prognosis of tinnitus.Furthermore, fecal transplantation may be used to treat tinnitus.}, }
@article {pmid39555739, year = {2024}, author = {Liu, X and Kang, W and Li, J and Li, X and Yang, P and Shi, M and Wang, Z and Wang, Y and Medina, ADPA and Liu, D and Zhu, F and Shen, H and Huang, K and Chen, X and Liu, Y}, title = {Melatonin Ameliorates Cadmium-Induced Liver Fibrosis Via Modulating Gut Microbiota and Bile Acid Metabolism.}, journal = {Journal of pineal research}, volume = {76}, number = {8}, pages = {e70005}, doi = {10.1111/jpi.70005}, pmid = {39555739}, issn = {1600-079X}, support = {//This study was funded by the National Natural Science Foundation of China (32102741) and Fundamental Research Funds for the Central Universities (Grant No. KJYQ2024010; KYT2023004)./ ; }, mesh = {Animals ; Mice ; Anti-Bacterial Agents/adverse effects ; Bile Acids and Salts/biosynthesis ; *Chemical and Drug Induced Liver Injury/drug therapy/etiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Intestinal Barrier Function/drug effects ; *Intestines/drug effects/metabolism ; Liver/drug effects/metabolism ; Liver Cirrhosis/chemically induced/drug therapy ; *Melatonin/pharmacology/therapeutic use ; Mice, Inbred C57BL ; *Cadmium/toxicity ; }, abstract = {Cadmium (Cd) is a widespread environmental contaminant with high toxicity to human health. Melatonin has been shown to improve Cd-induced liver damage. However, its mechanism has not yet been elucidated. In this study, we aimed to investigate the effects of melatonin on Cd-induced liver damage and fibrosis. A combination of 16S rRNA gene sequencing and mass spectrometry-based metabolomics was adopted to investigate changes in the gut microbiome and its metabolites on the regulation of melatonin in Cd-induced liver injury and fibrosis of mice. Further, nonabsorbable antibiotics, a fecal microbiota transplantation (FMT) program and intestine-specific farnesoid X receptor (FXR) knockout mice were employed to explore the mechanism of melatonin (MT) on liver injury and fibrosis in Cd treated mice. MT significantly improved hepatic inflammation, bile duct hyperplasia, liver damage, and liver fibrosis, with a notable decrease in liver bile acid levels in Cd-exposed mice. MT treatment remodeled the gut microbiota, improved gut barrier function, and reduced the production of gut-derived lipopolysaccharide (LPS). MT significantly decreased the intestinal tauro-β-muricholic acid levels, which are known as FXR antagonists. Notably, MT prominently activated the intestinal FXR signaling, subsequently inhibiting liver bile acid synthesis and decreasing hepatic inflammation in Cd-exposed mice. However, MT could not ameliorate Cd-induced liver damage and fibrosis in Abx-treated mice. Conversely, MT still exerted a protective effect on Cd-induced liver damage and fibrosis in FMT mice. Interestingly, MT failed to reverse liver damage and fibrosis in Cd-exposed intestinal epithelial cell-specific FXR gene knockout mice, indicating that intestinal FXR signaling mediated the protective effect of MT treatment. MT improves Cd-induced liver damage and fibrosis through reshaping the intestinal flora, activating the intestinal FXR-mediated suppression of liver bile acid synthesis and reducing LPS leakage in mice.}, }
@article {pmid39552646, year = {2024}, author = {Dong, X and Su, Y and Luo, Z and Li, C and Gao, J and Han, X and Yao, S and Wu, W and Tian, L and Bai, Y and Wang, G and Ren, W}, title = {Fecal microbiota transplantation alleviates cognitive impairment by improving gut microbiome composition and barrier function in male rats of traumatic brain injury following gas explosion.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1485936}, pmid = {39552646}, issn = {1664-302X}, abstract = {BACKGROUND: Dysbiosis of gut microbiota (GM) is intricately linked with cognitive impairment and the incidence of traumatic brain injury (TBI) in both animal models and human subjects. However, there is limited understanding of the impact and mechanisms of fecal microbiota transplantation (FMT) on brain and gut barrier function in the treatment of TBI induced by gas explosion (GE).<br><br>METHODS: We have employed FMT technology to establish models of gut microbiota dysbiosis in male rats, and subsequently conducted non-targeted metabolomics and microbiota diversity analysis to explore the bacteria with potential functional roles.<br><br>RESULTS: Hematoxylin-eosin and transmission electron microscopy revealed that GE induced significant pathological damage and inflammation responses, as well as varying degrees of mitochondrial impairment in neuronal cells in the brains of rats, which was associated with cognitive decline. Furthermore, GE markedly elevated the levels of regulatory T cell (Tregs)-related factors interleukin-10, programmed death 1, and fork head box protein P3 in the brains of rats. Similar changes in these indicators were also observed in the colon; however, these alterations were reversed upon transfer of normal flora into the GE-exposed rats. Combined microbiome and metabolome analysis indicated up-regulation of Clostridium_T and Allobaculum, along with activation of fatty acid biosynthesis after FMT. Correlation network analysis indirectly suggested a causal relationship between FMT and alleviation of GE-induced TBI. FMT improved intestinal structure and up-regulated expression of tight junction proteins Claudin-1, Occludin, and ZO-1, potentially contributing to its protective effects on both brain and gut.<br><br>CONCLUSION: Transplantation of gut microbiota from healthy rats significantly enhanced cognitive function in male rats with traumatic brain injury caused by a gas explosion, through the modulation of gut microbiome composition and the improvement of both gut and brain barrier integrity via the gut-brain axis. These findings may offer a scientific foundation for potential clinical interventions targeting gas explosion-induced TBI using FMT.}, }
@article {pmid39548908, year = {2024}, author = {Gopal, RK and Ganesh, PS and Pathoor, NN}, title = {Synergistic Interplay of Diet, Gut Microbiota, and Insulin Resistance: Unraveling the Molecular Nexus.}, journal = {Molecular nutrition &amp; food research}, volume = {68}, number = {23}, pages = {e2400677}, doi = {10.1002/mnfr.202400677}, pmid = {39548908}, issn = {1613-4133}, mesh = {*Gastrointestinal Microbiome/physiology ; *Insulin Resistance ; Humans ; *Diet/methods ; Dietary Fiber/administration &amp; dosage/pharmacology ; Animals ; Fatty Acids, Volatile/metabolism ; Diet, Mediterranean ; Dysbiosis ; Fecal Microbiota Transplantation ; Probiotics/administration &amp; dosage/pharmacology ; Polyphenols/pharmacology ; }, abstract = {This comprehensive review explores the intricate relationship between gut microbiota, diet, and insulin resistance, emphasizing the novel roles of diet-induced microbial changes in influencing metabolic health. It highlights how diet significantly influences gut microbiota composition, with different dietary patterns fostering diverse microbial communities. These diet-induced changes in the microbiome impact human metabolism by affecting inflammation, energy balance, and insulin sensitivity, particularly through microbial metabolites like short-chain fatty acids (SCFAs). Focusing the key mediators like endotoxemia and systemic inflammation, and introduces personalized microbiome-based therapeutic strategies, it also investigates the effects of dietary components-fiber, polyphenols, and lipids-on microbiota and insulin sensitivity, along with the roles of protein intake and amino acid metabolism. The study compares the effects of Western and Mediterranean diets on the microbiota-insulin resistance axis. Therapeutic implications, including probiotics, fecal microbiota transplantation (FMT), and personalized diets, are discussed. Key findings reveal that high-fat diets, especially those rich in saturated fats, contribute to dysbiosis and increased intestinal permeability, while high-fiber diets promote beneficial bacteria and SCFAs. The review underscores the future potential of food and microbiota interventions for preventing or managing insulin resistance.}, }
@article {pmid39548468, year = {2024}, author = {Song, Q and Gao, Y and Liu, K and Tang, Y and Man, Y and Wu, H}, title = {Gut microbial and metabolomics profiles reveal the potential mechanism of fecal microbiota transplantation in modulating the progression of colitis-associated colorectal cancer in mice.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {1028}, pmid = {39548468}, issn = {1479-5876}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Metabolomics ; Humans ; *Disease Progression ; *Colitis-Associated Neoplasms/microbiology/pathology/metabolism ; Mice, Inbred C57BL ; Male ; Colorectal Neoplasms/microbiology/pathology/metabolism ; Dextran Sulfate ; Metabolome ; Mice ; Female ; Azoxymethane ; Wnt Signaling Pathway ; Feces/microbiology ; }, abstract = {PURPOSE: Intestinal flora promotes the pathogenesis of colorectal cancer (CRC) through microorganisms and their metabolites. This study aimed to investigate the composition of intestinal flora in different stages of CRC progression and the effect of fecal microbiota transplantation (FMT) on CRC mice.<br><br>METHODS: The fecal microbiome from healthy volunteers (HC), colorectal adenoma (CRA), inflammatory bowel disease (IBD), and CRC patients were analyzed by 16s rRNA gene sequencing. In an azoxymethane (AOM)/dextran-sulfate-sodium (DSS)-induced CRC mouse, the effect of FMT from HC, CRA, CRC, and IBD patients on CRC mice was assessed by histological analysis. Expression of inflammation- EMT-associated proteins and Wnt/&#x3b2;-catenin pathway were assessed using qRT-PCR and western blot. The ratio of the fecal microorganisms and metabolomics alteration after FMT were also assessed.<br><br>RESULT: Prevotella, Faecalibacterium, Phascolarctobacterium, Veillonella, Alistipes, Fusobacterium, Oscillibacter, Blautia, and Ruminococcus abundance was different among HC, IBD, CRC, and CRA patients. HC-FMT alleviated disease progression and inflammatory response in CRC mice, inhibited splenic T help (Th)1 and Th17 cell numbers, and suppressed the EMT and Wnt/&#x3b2;-catenin pathways in tumor tissues of CRC mice. IBD-FMT, CRA-FMT, and CRC-FMT played deleterious roles; the CRC-FMT mice exhibited the most malignant phenotype. Compared with the non-FMT CRC mice, Muribaculaceae abundance was lower after FMT, especially lowest in the IBD-FMT group; while Lactobacillus abundance was higher after FMT and especially high in HC-FMT. Akkermansia and Ileibacterium abundance increased after FMT-HC compared to other groups. Metabolite correlation analysis revealed that Muribaculaceae abundance was significantly correlated with metabolites such as Betaine, LysoPC, and Soyasaponin III. Lactobacillus abundance was positively correlated with Taurocholic acid 3-sulfate, and Ileibacterium abundance was positively correlated with Linoleoyl ethanolamide.<br><br>CONCLUSION: The different intestinal microbiota communities of HC, IBD, CRA, and CRC patients may be attributed to the different modulation effects of FMT on CRC mice. CRC-FMT promoted, while HC-FMT inhibited the progress of CRC. Increased linoleoyl ethanolamide levels and abundance of Muribaculaceae, Akkermansia, and Ileibacterium and reduced Fusobacterium might participate in inhibiting CRC initiation and development. This study demonstrated that FMT intervention could restore the intestinal microbiota and metabolomics of CRC mice, suggesting FMT as a potential strategy for CRC therapy.}, }
@article {pmid39548040, year = {2024}, author = {Wang, J and Yang, R and Zhong, H and Liu, YJ}, title = {Fecal microbiota transplants in pediatric autism: opportunities and challenges.}, journal = {World journal of pediatrics : WJP}, volume = {20}, number = {12}, pages = {1201-1204}, pmid = {39548040}, issn = {1867-0687}, support = {82070823//National Natural Science Foundation of China/ ; }, }
@article {pmid39547534, year = {2025}, author = {Birch, CR and Paaske, SE and Jensen, MB and Baunwall, SMD and Ehlers, LH and Hvas, CL}, title = {Cost-effectiveness of faecal microbiota transplantation compared with vancomycin monotherapy for early Clostridioides difficile infection: economic evaluation alongside a randomized controlled trial.}, journal = {The Journal of hospital infection}, volume = {155}, number = {}, pages = {145-149}, doi = {10.1016/j.jhin.2024.11.003}, pmid = {39547534}, issn = {1532-2939}, mesh = {Humans ; *Fecal Microbiota Transplantation/economics/methods ; *Clostridium Infections/therapy/economics ; Cost-Benefit Analysis ; *Vancomycin/therapeutic use/economics ; *Anti-Bacterial Agents/economics/therapeutic use ; Male ; Middle Aged ; Female ; Aged ; Clostridioides difficile ; Treatment Outcome ; Adult ; }, abstract = {BACKGROUND: For Clostridioides difficile infection (CDI), faecal microbiota transplantation (FMT) is currently recommended for patients with three or more CDI episodes. A recent randomised controlled trial (RCT) show that FMT may be considered early, defined as intervention during the first or second CDI episode.<br><br>AIM: The aim was to investigate hospital costs of FMT as a complementary treatment compared with current standard care in patients with first or second CDI.<br><br>FINDINGS: Compared with standard care for first or second CDI, patients randomised to FMT had &#x20ac;1,645 lower hospital costs over 26 weeks owing to fewer admissions and hospital contacts and less medication use. In the sensitivity analyses, FMT remained cost-effective as long as the treatment cost of FMT stayed below approximately &#x20ac;1,572 per component, corresponding to a total cost of FMT treatment (two components) of &#x20ac;3,144.<br><br>CONCLUSION: FMT was cost-effective with both lower costs and greater effectiveness than current standard care involving vancomycin monotherapy. The findings were robust to sensivity analyses, with a threshold cost for one FMT treatment consisting of two components of &#x20ac;3,144.}, }
@article {pmid39547500, year = {2025}, author = {Huang, ZB and Zhang, GP and Lu, CX and Gong, C and Gao, X and Lin, Y and Su, P and Xu, W and Lin, Y and Lin, N and Wu, X and Chen, X and Zheng, T and Zheng, X}, title = {Gut microbiota-derived 3-indoleacetic acid confers a protection against sepsis-associated encephalopathy through microglial aryl hydrocarbon receptors.}, journal = {Experimental neurology}, volume = {384}, number = {}, pages = {115055}, doi = {10.1016/j.expneurol.2024.115055}, pmid = {39547500}, issn = {1090-2430}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Receptors, Aryl Hydrocarbon/metabolism ; *Sepsis-Associated Encephalopathy/metabolism ; *Indoleacetic Acids/pharmacology ; Male ; Mice ; *Microglia/drug effects/metabolism ; *Mice, Inbred C57BL ; Humans ; Middle Aged ; Female ; Aged ; Fecal Microbiota Transplantation ; Sepsis/complications/metabolism ; }, abstract = {BACKGROUND: The gut microbiota significantly contributes to the pathogenesis of central nervous system disorders. Among the bioactive molecules produced by the gut microbiota, 3-indoleacetic acid (IAA) has been shown to attenuate oxidative stress and inflammatory responses. This experiment aimed to determine the impacts of IAA on sepsis-associated encephalopathy (SAE) and the underlying mechanisms.<br><br>METHODS: A total of 34 septic patients and 24&#xa0;healthy controls were included in the analysis of the clinical correlation between fecal IAA and septic encephalopathy. Fecal microbiota transplantation was used to verify the role of the gut microbiota and its metabolites in SAE. Male C57BL/6 mice aged six to eight weeks, pre-treated with IAA via oral gavage, were subjected to the cecal ligation and puncture (CLP) procedures. This treatment was administered either in combination with an aryl hydrocarbon receptor (AhR) antagonist, CH223191, or a CSF1R inhibitor, PLX3397, to eliminate microglia. Both immunofluorescence staining and enzyme-linked immunosorbent assays were used to evaluate microglia activation and inflammatory cytokine secretion. Behavioral assessments were conducted to quantify neurological deficits.<br><br>RESULTS: A decreased fecal level of IAA was observed in the patients with sepsis-associated delirium (SAD), a manifestation of SAE. A reduced IAA level was significantly associated with worsen clinical outcomes. Fecal microbiota transplantation from the SAD patients induced an SAE-like phenotype in mice, but supplementing exogenous IAA improved the SAE-like phenotype, mediated by microglia. IAA effectively binded with the aryl hydrocarbon receptor (AhR). Furthermore, IAA increased the nuclear activity of AhR in the lipopolysaccharide (LPS)-treated microglial cells, leading to reduced secretion of inflammatory cytokines. The AhR inhibitor CH223191 counteracted the protective effect of IAA against SAE in mice.<br><br>CONCLUSIONS: Gut microbiota-derived IAA confers a protection against SAE by activating AhR in microglia, improving neuronal and cognitive impairments. Thus, IAA holds the promise as a potential therapeutic agent for managing SAE.}, }
@article {pmid39547012, year = {2024}, author = {Wang, J and Hou, Y and Mu, L and Yang, M and Ai, X}, title = {Gut microbiota contributes to the intestinal and extraintestinal immune homeostasis by balancing Th17/Treg cells.}, journal = {International immunopharmacology}, volume = {143}, number = {Pt 3}, pages = {113570}, doi = {10.1016/j.intimp.2024.113570}, pmid = {39547012}, issn = {1878-1705}, mesh = {Humans ; *Th17 Cells/immunology ; *T-Lymphocytes, Regulatory/immunology ; *Gastrointestinal Microbiome/immunology ; Animals ; *Homeostasis ; Intestines/immunology/microbiology ; Probiotics ; Fecal Microbiota Transplantation ; }, abstract = {Gut microbiota is generally considered to play an important role in host health due to its extensive immunomodulatory activities. Th17 and Treg cells are two important CD4+ T cell subsets involved in immune regulation, and their imbalance is closely tied to many immune diseases. Recently, abundant researches have highlighted the importance of gut microbiota in supporting intestinal and extraintestinal immunity through the balance of Th17 and Treg cells. Here, we presented a comprehensive review of these findings. This review first provided an overview of gut microbiota, along with Th17/Treg cell differentiation and cytokine production. Subsequently, the review summarized the regulatory effects of gut microbiota (in terms of species, components, and metabolites) on the Th17/Treg cell balance in the local intestines and extraintestinal organs, such as lung, liver, brain, kidney, and bone. Specifically, the Th17 and Treg cells that can be modulated by gut microbiota originate not only from the gut and extraintestinal organs, but also from peripheral blood and spleen. Then, the microbial therapeutics, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT), were also reviewed because of their therapeutic potentials in addressing intestinal and extraintestinal diseases via the Th17/Treg axis. Finally, the review discussed the clinical applications and future study prospects of microbial therapeutics by targeting the Th17/Treg cell balance. In conclusion, this review focused on elucidating the regulatory effects of gut microbiota in balancing Th17/Treg cells to maintain intestinal and extraintestinal immune homeostasis, contributing to the further development and promotion of microbial therapeutics.}, }
@article {pmid39546851, year = {2024}, author = {Peña-Ocaña, BA and Silva-Flores, M and Shotaro, T and García-Gálvez, L and Hernández-Esquivel, L and Robledo-Cadena, DX and Barrera-Oviedo, D and Pérez-Torres, I and Tostado-Islas, O and Maeda, T and Rodríguez-Zavala, JS and Marín-Hernández, &#xc1; and García-Contreras, R and Jasso-Chávez, R}, title = {Transplant of gut microbiota ameliorates metabolic and heart disorders in rats fed with a hypercaloric diet by modulating microbial metabolism and diversity.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {181}, number = {}, pages = {117667}, doi = {10.1016/j.biopha.2024.117667}, pmid = {39546851}, issn = {1950-6007}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Male ; Rats ; *Metabolic Syndrome/microbiology/metabolism/therapy/diet therapy ; Heart Diseases/microbiology/metabolism ; Rats, Wistar ; Probiotics/administration &amp; dosage/therapeutic use/pharmacology ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/methods ; Diet, High-Fat/adverse effects ; Feces/microbiology ; Bacteria/metabolism/classification ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Metabolic syndrome (MS) is a cluster of metabolic disorders which have a tight correlation with dysbiosis of gut microbiota (GM) that have to be treated to avoid higher risks for health. In this work, probiotics obtained from healthy cultured GM were provided to rats with metabolic syndrome (MSR) as therapy in treating MS through the correction of dysbiosis. MSR showed obesity, high blood pressure, abnormal blood chemistry parameters and high heart rate respect to control rats (CNTR). Cultivated GM from feces of MSR in media favoring anaerobic species, showed dysbiosis as judged by differences in the 16S rRNA metabarcoding analysis and by affected intermediary metabolism (methane and SCFA production, nutrients consumption and enzyme activities) compared to CNTR. The metabarcoding analysis of cultured healthy GM identified 211 species, which were further transplanted alive in MSR once a week for 9 weeks. Thereafter, in transplanted MSR the excess of Clostridium and Lactobacillus diminished, while Prevotella, Eubacterium, Faecalibacterium and methanogens, among others increased, leading to the recovery of the microbial metabolic capacity. The presence of butyric acid-producing bacteria in the transplanted GM correlated with increased levels of anti-inflammatory cytokines. Therefore, transplanted MSR recovered the normal levels of weight, blood glucose, triglycerides and cholesterol as well as the heart function. Data suggested that the great diversity of species contained in the GM transplanted restored the microbial metabolism, consuming excessive nutrients and secondary metabolites produced by MS. The use of cultivated GM as probiotics may be a safer alternative for the treatment of different diseases.}, }
@article {pmid39545921, year = {2025}, author = {Ullern, A and Holm, K and Røssevold, AH and Andresen, NK and Bang, C and Lingjærde, OC and Naume, B and Hov, JR and Kyte, JA}, title = {Gut microbiota diversity is prognostic and associated with benefit from chemo-immunotherapy in metastatic triple-negative breast cancer.}, journal = {Molecular oncology}, volume = {19}, number = {4}, pages = {1229-1243}, pmid = {39545921}, issn = {1878-0261}, support = {2017100//Helse S&#xf8;r-&#xd8;st RHF/ ; 2017122//Helse S&#xf8;r-&#xd8;st RHF/ ; 182632//Kreftforeningen/ ; 214972/WT_/Wellcome Trust/United Kingdom ; 214972/WT_/Wellcome Trust/United Kingdom ; 802544/ERC_/European Research Council/International ; }, mesh = {Aged ; Female ; Humans ; Middle Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use ; *Gastrointestinal Microbiome/genetics/drug effects ; *Immunotherapy ; Neoplasm Metastasis ; Prognosis ; *Triple Negative Breast Neoplasms/drug therapy/microbiology/pathology/therapy ; }, abstract = {The gut microbiota influences multiple aspects of human health and disease. Several studies have indicated an association between the gut microbiota and response to immune checkpoint inhibitors in various cancers, but there is scarce data from breast cancer. The randomized ALICE trial demonstrated improved progression-free survival (PFS) from adding the programmed cell death 1 ligand 1 (PD-L1) inhibitor atezolizumab (atezo) to immunomodulating chemotherapy (chemo) in metastatic triple-negative breast cancer (mTNBC), even for PD-L1[negative] disease. Herein, we investigated the microbiota composition and dynamics in the ALICE patients and their association with clinical outcome, by analyzing fecal samples collected at baseline and after 8 weeks. We applied 16S (V3-V4) rRNA sequencing to characterize the diversity and taxonomic composition. Kaplan-Meier and Cox proportional hazard models were used for time-to-event analyses. We found that high alpha diversity by Faith's phylogenetic diversity (PD) at baseline was associated with prolonged PFS in the total study population and in the atezo-chemo arm, but not in the placebo-chemo arm. Moreover, Faith's PD appeared to be predictive of benefit from atezolizumab. Patients with high Faith's PD exhibited a PFS hazard ratio of 0.34 (P = 0.018) in favor of the atezo-chemo arm, compared to 0.83 (P = 0.62) in the low Faith's PD group. Faith's PD was significantly reduced during treatment. At baseline, Bifidobacterium was significantly overrepresented in patients without clinical benefit in the atezo-chemo arm, but not in the placebo-chemo arm. These findings suggest that alpha diversity by Faith's PD should be further investigated as a prognostic and predictive biomarker in patients with mTNBC receiving chemo-immunotherapy.}, }
@article {pmid39543390, year = {2024}, author = {Islam, J and Ohtani, N and Shimizu, Y and Tanimizu, M and Goto, Y and Sato, M and Makino, E and Shimada, T and Ueda, C and Matsuo, A and Suyama, Y and Sakai, Y and Karrow, NA and Yoneyama, H and Hirakawa, R and Furukawa, M and Tanaka, H and Nochi, T}, title = {Freeze-dried fecal microorganisms as an effective biomaterial for the treatment of calves suffering from diarrhea.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28078}, pmid = {39543390}, issn = {2045-2322}, support = {Livestock Promotional Subsidy//Japan Racing Association/ ; 20K15478//Japan Society for the Promotion of Science/ ; 22H00393//Japan Society for the Promotion of Science/ ; 18H03969//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Cattle ; *Diarrhea/therapy/microbiology/veterinary ; *Fecal Microbiota Transplantation/methods ; *Feces/microbiology ; *Freeze Drying ; Gastrointestinal Microbiome ; Cattle Diseases/therapy/microbiology ; Biocompatible Materials ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapeutic modality for treating neonatal calf diarrhea. Several practical barriers, including donor selection, fecal collection, and a limited timeframe for FMT, are the main constraints to using fresh feces for implementing on-farm FMT. We report the utility of FMT with pretreated ready-to-use frozen (F) or freeze-dried (FD) microorganisms for treating calf diarrhea. In total, 19 FMT (F-FMT, n = 10 and FD-FMT, n = 9) treatments were conducted. Both FMT treatments were 100% clinically effective; however, multi-omics analysis showed that FD-FMT was superior to F-FMT. Machine learning analysis with SourceTracker confirmed that donor microbiota was retained four times better in the recipient calves treated with FD-FMT than F-FMT. A predictive model based on receiver operating characteristic curve analysis and area under the curve showed that FD-FMT was more discriminative than F-FMT of the observed changes in microbiota and metabolites during disease recovery. These results provide new insights into establishing methods for preparing fecal microorganisms to increase the quality of FMT in animals and may contribute to FMT in humans.}, }
@article {pmid39541983, year = {2024}, author = {Urtecho, G and Moody, T and Huang, Y and Sheth, RU and Richardson, M and Descamps, HC and Kaufman, A and Lekan, O and Zhang, Z and Velez-Cortes, F and Qu, Y and Cohen, L and Ricaurte, D and Gibson, TE and Gerber, GK and Thaiss, CA and Wang, HH}, title = {Spatiotemporal dynamics during niche remodeling by super-colonizing microbiota in the mammalian gut.}, journal = {Cell systems}, volume = {15}, number = {11}, pages = {1002-1017.e4}, doi = {10.1016/j.cels.2024.10.007}, pmid = {39541983}, issn = {2405-4720}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Fecal Microbiota Transplantation/methods ; Mice, Inbred C57BL ; Gastrointestinal Tract/microbiology ; Dysbiosis/microbiology ; Mammals/microbiology ; Feces/microbiology ; }, abstract = {While fecal microbiota transplantation (FMT) has been shown to be effective in reversing gut dysbiosis, we lack an understanding of the fundamental processes underlying microbial engraftment in the mammalian gut. Here, we explored a murine gut colonization model leveraging natural inter-individual variations in gut microbiomes to elucidate the spatiotemporal dynamics of FMT. We identified a natural "super-donor" consortium that robustly engrafts into diverse recipients and resists reciprocal colonization. Temporal profiling of the gut microbiome showed an ordered succession of rapid engraftment by early colonizers within 72 h, followed by a slower emergence of late colonizers over 15-30 days. Moreover, engraftment was localized to distinct compartments of the gastrointestinal tract in a species-specific manner. Spatial metagenomic characterization suggested engraftment was mediated by simultaneous transfer of spatially co-localizing species from the super-donor consortia. These results offer a mechanism of super-donor colonization by which nutritional niches are expanded in a spatiotemporally dependent manner. A record of this paper's transparent peer review process is included in the supplemental information.}, }
@article {pmid39540836, year = {2024}, author = {Charles, P and Kumar, S and Girish Kumar, CP and Parameswaran, S and Viswanathan, P and Nachiappa Ganesh, R}, title = {Association of gut microbiota with allograft injury in kidney transplant recipients: a comparative profiling through 16S metagenomics and quantitative PCR.}, journal = {Journal of medical microbiology}, volume = {73}, number = {11}, pages = {}, doi = {10.1099/jmm.0.001934}, pmid = {39540836}, issn = {1473-5644}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; *RNA, Ribosomal, 16S/genetics ; Female ; Middle Aged ; *Metagenomics/methods ; Adult ; Prospective Studies ; Longitudinal Studies ; *Graft Rejection/microbiology ; Real-Time Polymerase Chain Reaction/methods ; Bacteria/classification/genetics/isolation &amp; purification ; Feces/microbiology ; Allografts/microbiology ; Transplant Recipients ; }, abstract = {Introduction. The existence of a mutual relationship between gut microbiota and immune homeostasis highlights its importance in the context of kidney transplantation.Gap statement. The translational utility of gut microbiota as a biomarker for allograft injury has not been assessed before.Aim. In this study, we aimed to characterize the gut microbial diversity in kidney transplant recipients and investigate the alterations in the gut microbial composition in association with allograft injury such as histopathological graft rejection and calcineurin inhibitor toxicity. In addition, we compared the gut microbial quantitation using 16S metagenomics and quantitative PCR (qPCR) to assess its translational utility.Methodology. In this prospective longitudinal cohort study, we enrolled 38 kidney transplant recipients and collected serial faecal specimens (n=114), once before the induction therapy, and twice after transplant, during the first and third month. We characterized the gut microbial composition through 16S rRNA sequencing and qPCR from the DNA isolates of the samples. The recipients were clinically followed up for a median of 600 days post-transplant. Histopathological evidence of allograft rejection and calcineurin inhibitor toxicity were used for the correlational analysis with gut microbial diversity.Results. Significant differences in the gut microbial diversity were observed between the pre- and post-transplant samples. Pre-transplant gut microbiota revealed a higher relative abundance of phylum Bacteroidetes in the allograft rejection group, and a higher relative abundance of phylum Firmicutes was observed in the histopathological features of calcineurin inhibitor toxicity (hCNI toxicity) group. We found a high concordance between 16S metagenomics and qPCR outputs for assessing the gut microbial diversity. Furthermore, the receiver operating characteristic curve analysis has also proven that the pre-transplant levels of gut microbial dysbiosis, as a potential predictive biomarker for allograft injury.Conclusion. Our pilot study found a strong statistical association of gut microbial dysbiosis with kidney allograft injury, highlighting the potential of gut microbiota as a predictive biomarker and that qPCR serves as a more reliable and economic tool for assessing dysbiosis paving the way for its translational utility.}, }
@article {pmid39539436, year = {2024}, author = {Abood, NA and Kadhim, DJ and Hussein, RJ}, title = {Medication-related burden among Iraqi patients with ulcerative colitis: a cross-sectional study.}, journal = {Journal of medicine and life}, volume = {17}, number = {8}, pages = {800-805}, pmid = {39539436}, issn = {1844-3117}, mesh = {Humans ; *Colitis, Ulcerative/drug therapy ; Iraq ; Male ; Cross-Sectional Studies ; Female ; Adult ; Surveys and Questionnaires ; Middle Aged ; Cost of Illness ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurring periods of inflammation and remission, primarily affecting the colon. The concept of medication-related burden, which refers to the adverse effects experienced by patients due to conventional medical treatments, is relatively new in the field. This study aimed to measure medication-related burden among patients with ulcerative colitis in Iraq. The study was conducted at the Gastroenterology and Hepatology Teaching Hospital, Medical City, Baghdad, Iraq, from December 2022 to May 2023. We used the Arabic version of the Living with Medicines Questionnaire version 3 (LMQ-3) to explore medication-related burdens experienced by patients with UC. Eighty-six patients with ulcerative colitis were included. The mean of the total medication-related burden score was 107.5 ± 20.7. The findings showed that 45.3% of patients with UC had a moderate degree of medication-related burden, followed by minimum burden (44.2%), high burden (5.8%), and no burden (4.7%). The lowest median burden scores emerged in five domains: interactions with healthcare professionals, practical difficulties with medication use, medication side effects, medication effectiveness, and the impact on daily life. Conversely, the highest-burden scores were noted in the cost, concerns about medication use, and autonomy to vary the regimen domains. In multivariate analysis, none of the patient-related variables was independently correlated with the total medication-related burden score. A large proportion of the patients with UC who participated in the current study reported varying degrees of medication-related burden, with the majority having a minimum to moderate medication-related burden.}, }
@article {pmid39539028, year = {2024}, author = {Kovynev, A and Ying, Z and Zhang, S and Olgiati, E and Lambooij, JM and Visentin, C and Guigas, B and Ducarmon, QR and Rensen, PCN and Schönke, M}, title = {Timing Matters: Late, but Not Early, Exercise Training Ameliorates MASLD in Part by Modulating the Gut-Liver Axis in Mice.}, journal = {Journal of pineal research}, volume = {76}, number = {8}, pages = {e70003}, doi = {10.1111/jpi.70003}, pmid = {39539028}, issn = {1600-079X}, support = {//This work was supported by the Novo Nordisk Foundation (grant NNF18OC0032394 to M.S.), The Netherlands Cardiovascular Research Initiative CVON-GENIUS-2 (grant to P.C.N.R.), the Chinese Scholarship Council (grants to Z.Y. and S.Z.). A.K. is supported by a PhD grant from Leiden University Medical Center (to M.S.)./ ; }, mesh = {Animals ; Mice ; Male ; *Physical Conditioning, Animal ; *Gastrointestinal Microbiome ; *Liver/metabolism ; Fatty Liver/therapy/metabolism ; Non-alcoholic Fatty Liver Disease/metabolism/therapy ; Diet, High-Fat ; Mice, Transgenic ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development. Twenty weeks old male APOE*3-Leiden.CETP mice were fed a high fat-high cholesterol diet to induce MASLD and treadmill-trained for 1 h five times per week for 12 weeks either early (ZT13; E-RUN) or late (ZT22; L-RUN) in the dark phase while corresponding sedentary groups (E-SED and L-SED) did not. Late, but not early exercise training decreased the MASLD score, body weight, fat mass, and liver triglycerides, accompanied by an altered composition of the gut microbiota. Specifically, only late exercise training increased the abundance of short-chain fatty acid-producing bacterial families and genera, such as Akkermansia, Lachnospiraceae, and Rikenella. To assess the role of the gut microbiota in training-induced effects, the study was repeated and trained (ZT22 only, RUN) or sedentary mice (SED) served as fecal donors for sedentary recipient mice (RUN FMT and SED FMT). Fecal microbiota transplantation reduced liver weight and plasma triglycerides in RUN FMT compared to SED FMT and tended to lower the MASLD score and liver triglycerides. Timing of exercise training is a critical factor for the positive effect on MASLD in this preclinical model, and the effect of late exercise is partially mediated via the gut-liver axis.}, }
@article {pmid39538028, year = {2024}, author = {Emile, SH and Wignakumar, A and Horesh, N and Garoufalia, Z and Strassmann, V and Boutros, M and Wexner, SD}, title = {Systematic literature review and meta-analysis of surgical treatment of complete rectal prolapse in male patients.}, journal = {Techniques in coloproctology}, volume = {28}, number = {1}, pages = {158}, pmid = {39538028}, issn = {1128-045X}, mesh = {Adult ; Humans ; Male ; Middle Aged ; Constipation/etiology/surgery/epidemiology ; Digestive System Surgical Procedures/methods/adverse effects ; Fecal Incontinence/etiology/epidemiology ; Operative Time ; Perineum/surgery ; Postoperative Complications/etiology/epidemiology ; *Rectal Prolapse/surgery ; Rectum/surgery ; Recurrence ; Surgical Mesh ; Treatment Outcome ; }, abstract = {BACKGROUND: Rectal prolapse often affects women but may also affect men. This systematic review aimed to provide outcomes of surgery for complete rectal prolapse reported in studies with a predominantly male population.<br><br>METHODS: This PRISMA-compliant systematic literature review searched PubMed and Scopus between January 2000 and February 2024; Google Scholar was queried for studies reporting outcomes of complete rectal prolapse surgery in predominately (>&#x2009;90%) male populations. Main outcome measures were recurrence, complications, operative time, and bowel function.<br><br>RESULTS: Eight studies (452 patients; median age 45.6&#xa0;years) were included; 80.5% of patients underwent abdominal procedures whereas 19.5% underwent perineal procedures. The prevalence&#xa0;of recurrence was 11.2% after ventral mesh rectopexy (VMR), 0.8% after posterior mesh rectopexy (PMR), 0 after resection rectopexy, and 19.3% after perineal procedures. The prevalence&#xa0;of complications was 13.9% after VMR, 13.1% after PMR, 43.3% after resection rectopexy, and 17.4% after perineal procedures. The most improvement in constipation was noted&#xa0;after resection rectopexy (83.3-100%) and in fecal incontinence (FI) was noted&#xa0;after posterior mesh rectopexy (86.4-90%). Abdominal procedures had lower rates of recurrence (6% vs. 19.3%, RR 0.50, 95%&#xa0;CI 0.21-1.18, p&#x2009;=&#x2009;0.113), similar complication rates (14.3% vs. 13.6%, RR 0.41, 95%&#xa0;CI 0.06-2.9, p&#x2009;=&#x2009;0.374), and longer operative times (116&#x2009;&#xb1;&#x2009;47.2 vs. 74.2&#x2009;&#xb1;&#x2009;23.6&#xa0;min, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Treatment of rectal prolapse in male patients undergoing abdominal procedures was associated with longer operative times, lower recurrence rates, and similar complications to perineal procedures. PMR and resection rectopexy had the lowest recurrence. The most improvement in FI and constipation was noted after PMR and resection rectopexy, respectively.}, }
@article {pmid39536754, year = {2024}, author = {Wang, T and Fan, Y and Tan, S and Wang, Z and Li, M and Guo, X and Yu, X and Lin, Q and Song, X and Xu, L and Li, L and Li, S and Gao, L and Liang, X and Li, C and Ma, C}, title = {Probiotics and their metabolite spermidine enhance IFN-γ[+]CD4[+] T cell immunity to inhibit hepatitis B virus.}, journal = {Cell reports. Medicine}, volume = {5}, number = {11}, pages = {101822}, pmid = {39536754}, issn = {2666-3791}, mesh = {*Probiotics/pharmacology ; *Interferon-gamma/immunology/metabolism ; Animals ; *CD4-Positive T-Lymphocytes/immunology ; *Hepatitis B virus/immunology/drug effects ; *Spermidine/pharmacology ; Humans ; Mice ; Mice, Inbred C57BL ; Autophagy/drug effects ; Hepatitis B Surface Antigens/immunology ; Male ; Hepatitis B, Chronic/immunology ; Liver/immunology/metabolism ; Female ; Virus Replication/drug effects ; }, abstract = {The therapeutic potential of commensal microbes and their metabolites is promising in the functional cure of chronic hepatitis B virus (HBV) infection, which is defined as hepatitis B surface antigen (HBsAg) loss. Here, using both specific-pathogen-free and germ-free mice, we report that probiotics significantly promote the decline of HBsAg and inhibit HBV replication by enhancing intestinal homeostasis and provoking intrahepatic interferon (IFN)-γ[+]CD4[+] T cell immune response. Depletion of CD4[+] T cells or blockage of IFN-γ abolishes probiotics-mediated HBV inhibition. Specifically, probiotics-derived spermidine accumulates in the gut and transports to the liver, where it exhibits a similar anti-HBV effect. Mechanistically, spermidine enhances IFN-γ[+]CD4[+] T cell immunity by autophagy. Strikingly, administration of probiotics in HBV patients reveals a preliminary trend to accelerate the decline of serum HBsAg. In conclusion, probiotics and their derived spermidine promote HBV clearance via autophagy-enhanced IFN-γ[+]CD4[+] T cell immunity, highlighting the therapeutic potential of probiotics and spermidine for the functional cure of HBV patients.}, }
@article {pmid39534584, year = {2024}, author = {Hrubesz, G and Leigh, J and Ng, TL}, title = {Understanding the relationship between breast cancer, immune checkpoint inhibitors, and gut microbiota: a narrative review.}, journal = {Translational breast cancer research : a journal focusing on translational research in breast cancer}, volume = {5}, number = {}, pages = {31}, pmid = {39534584}, issn = {2218-6778}, abstract = {BACKGROUND AND OBJECTIVE: The composition of gut microbiota plays an important role in predicting and influencing outcomes of cancer treated with immunotherapy. Our objective is to summarize the role of gut microbiota and immunotherapy in breast cancer.<br><br>METHODS: A systematic search from inception until July 2024 of key search terms including immunity, breast neoplasm, gastrointestinal microbiome/microbiota, fecal microbiota transplantation, pro- and prebiotics, antibiotics and immunotherapy using EMBASE, MEDLINE and CENTRAL was conducted. The results were screened by two reviewers independently and synthesized and presented descriptively.<br><br>KEY CONTENT AND FINDINGS: Thirteen studies (5 clinical, 8 pre-clinical) met the eligibility criteria and were published from 2020-2024. Clinical studies showed that the composition and diversity of gut microbiota was associated with patient response to immunotherapy. In pre-clinical studies, dysbiotic states induced by obesity, antibiotics, and diet were associated with immunosuppression and influenced response to programmed cell death-ligand 1 (PD-L1) inhibitors. Microbiota-modulating treatments such as probiotics showed the ability to enhance response to immunotherapy, indicating their potential use as adjunct therapies in breast cancer treatment.<br><br>CONCLUSIONS: The composition of gut microbiota could help predict the chance of response to immunotherapy, and modulating gut microbiota has the potential to enhance the efficacy of chemo-immunotherapy in breast cancer. However, the available data relating to breast cancer are limited. Larger prospective studies are required to further elucidate their role as a biomarker and treatment.}, }
@article {pmid39534519, year = {2024}, author = {Jeyaraman, N and Jeyaraman, M and Mariappan, T and Muthu, S and Ramasubramanian, S and Sharma, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Insights of gut-liver axis in hepatic diseases: Mechanisms, clinical implications, and therapeutic potentials.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {15}, number = {6}, pages = {98146}, pmid = {39534519}, issn = {2150-5349}, abstract = {With the rising prevalence of chronic liver diseases worldwide, there exists a need to diversify our artillery to incorporate a plethora of diagnostic and therapeutic methods to combat this disease. Currently, the most common causes of liver disease are non-alcoholic fatty liver disease, hepatitis, and alcoholic liver disease. Some of these chronic diseases have the potential to transform into hepatocellular carcinoma with advancing fibrosis. In this review, we analyse the relationship between the gut and liver and their significance in liver disease. This two-way relationship has interesting effects on each other in liver diseases. The gut microbiota, through its metabolites, influences the metabolism in numerous ways. Careful manipulation of its composition can lead to the discovery of numerous therapeutic potentials that can be applied in the treatment of various liver diseases. Numerous cohort studies with a pan-omics approach are required to understand the association between the gut microbiome and hepatic disease progression through which we can identify effective ways to deal with this issue.}, }
@article {pmid39534419, year = {2024}, author = {Wang, J and Meng, Y and Guo, ZG}, title = {Contribution of gut microbiota to the development of Crohn's disease: Insights gained from fecal microbiota transplantation studies in mice.}, journal = {World journal of gastroenterology}, volume = {30}, number = {41}, pages = {4514-4517}, pmid = {39534419}, issn = {2219-2840}, mesh = {Animals ; Humans ; Mice ; Adipose Tissue/immunology ; *Crohn Disease/microbiology/immunology/therapy ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/immunology ; Intestines/microbiology/immunology ; Mesentery ; }, abstract = {We would like to present some new thoughts on the publication in the journal published in August 2024 in World Journal of Gastroenterology. We specifically focused on the alterations in the intestinal tract, mesenteric adipose tissue (MAT), and systemic inflammatory changes in mice following fecal flora transplantation into a mouse model of Crohn's disease (CD). Accumulating evidence suggests that the occurrence of CD is influenced by environmental factors, host immune status, genetic susceptibility, and flora imbalance. One microbiota-based intervention, fecal microbiota transplantation, has emerged as a potential treatment option for CD. The MAT is considered a "second barrier" around the inflamed intestine. The interaction between gut microbes and inflammatory changes in MAT has attracted considerable interest. In the study under discussion, the authors transplanted fetal fecal microorganisms from patients with CD and clinically healthy donors, respectively, into 2,4,6-trinitrobenzene sulfonic acid-induced CD mice. The research explored the complex interplay between MAT, creeping fat, inflammation, and intestinal flora in CD by evaluating intestinal and mesenteric lesions, along with the systemic inflammatory state in the mice. This article provides several important insights. First, the transplantation of intestinal flora holds significant potential as a therapeutic strategy for CD, offering hope for patients with CD. Second, it presents a novel approach to the diagnosis and treatment of CD: The inflammatory response in CD could potentially be assessed through pathological or imaging changes in the MAT, and CD could be treated by targeting the inflammation of the MAT.}, }
@article {pmid39529641, year = {2024}, author = {Kirsch, P and Rauch, J and Delau, O and Axelrad, J and Chang, S and Shaukat, A}, title = {Prevalence of Active Pouch Symptoms and Patient Perception of Symptom Control and Quality of Life in an Outpatient Practice.}, journal = {Gastro hep advances}, volume = {3}, number = {8}, pages = {1069-1078}, pmid = {39529641}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Pouchitis is an inflammatory condition affecting the ileal pouch in patients' status after ileal pouch anal anastomosis (IPAA). This affects a significant portion of IPAA patients. Our aim was to study the prevalence of active pouch symptoms among currently treated outpatients with endoscopic pouchitis and understand patients' perspective of disease control and quality of life.<br><br>METHODS: We cross-sectionally reviewed the medical charts of patients who had undergone pouchoscopy at NYU Langone Health from 2010 to 2022 and recorded demographic, clinical, and endoscopic data. Based on the most recent data in the medical record, we defined active pouch symptoms as 2 or more current clinical symptoms and "endoscopic pouchitis" as "moderate" or "severe" by pouchoscopy. We also administered surveys in March 2023 to 296 patients with an IPAA to understand symptom control, quality of life, and interest in fecal microbiota transplant.<br><br>RESULTS: We identified 282 unique patients. The median age of patients was 46 (interquartile range 33-59), with 54.3% males. Of these, 37.2% of patients currently had active pouch symptoms, 36.9% had endoscopic pouchitis, and 14.9% met the criteria for both. Of the 296 surveys sent to patients with IPAA, 74 (25%) responded. The median age of respondents was 49.5 (interquartile range 34-62). 59.5% were&#xa0;male. Average treatment satisfaction score (scale of 0-10) was&#xa0;6.4 and quality of life score was 5.8. A majority (64.9%)&#xa0;expressed interest in fecal microbiota transplant.<br><br>CONCLUSION: Outpatients with active pouch symptoms or endoscopic pouchitis have high prevalence of active disease and report ongoing symptoms. The results underscore the inadequacy of current treatments and highlight the need for additional therapeutic options.}, }
@article {pmid39524804, year = {2024}, author = {Zhang, Y and Wu, Y and Guan, Y and Lu, Y and Zhu, W and Ping, F and Wang, Y}, title = {Maidong Dishao Decoction mitigates submandibular gland injury in NOD mice through modulation of gut microbiota and restoration of Th17/Treg immune balance.}, journal = {Heliyon}, volume = {10}, number = {21}, pages = {e38421}, pmid = {39524804}, issn = {2405-8440}, abstract = {BACKGROUND: Primary Sjogren's syndrome (pSS) is a common chronic autoimmune disease that presents limited treatment options and poses significant challenges for patients. Maidong Dishao Decoction (MDDST), a traditional Chinese medicine compound, has demonstrated potential in alleviating dryness symptoms associated with pSS. Therefore, it is important to study the specific mechanism of its therapeutic effect.<br><br>OBJECTIVE: This study aims to investigate the effects of MDDST on gut microbiota, short-chain fatty acids (SCFAs), and the Th17/Treg immune balance in non-obese diabetes (NOD) mice.<br><br>METHODS: The study employed ultrahigh-performance liquid chromatography coupled with quadrupole-exactive mass spectrometry (UHPLC-QE-MS) to identify the primary components of MDDST. Subsequently, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assays (ELISA), and flow cytometry analyses were conducted to evaluate the therapeutic effects of MDDST in NOD mice. Additionally, 16S rDNA sequencing and gas chromatography-mass spectrometry (GC-MS) were utilized to assess the influence of MDDST on gut microbiota and SCFAs. Finally, fecal microbiota transplantation (FMT) and SCFA-based interventions were performed to elucidate the mechanisms through which MDDST exerts its effects.<br><br>RESULTS: The research findings demonstrate that MDDST exerts therapeutic effects on NOD mice, primarily manifested as reduced inflammation, decreased water intake, ameliorated pathological changes and lowered levels of Sjogren's syndrome antigen A (SSA) and immunoglobulin G (IgG). Additionally, MDDST significantly decreased serum levels of interleukin-6 (IL-6) and interleukin-17 (IL-17), while enhancing levels of interleukin-10 (IL-10) and transforming growth factor beta (TGF-&#x3b2;), thereby regulating the Th17/Treg immune balance. Further investigations revealed that MDDST treatment induces alterations in gut microbiota composition and elevates SCFA levels in the gut. Subsequent FMT and SCFA intervention experiments demonstrated a downregulation of pSS-related phenotypes.<br><br>CONCLUSION: In summary, MDDST demonstrates protective effects against pSS by restoring the balance between Th17 and Treg cells. The therapeutic effects can be partially attributed to its regulation of gut microbiota and SCFAs. Our finding provides a new option for treating pSS.}, }
@article {pmid39533632, year = {2024}, author = {Philips, CA and Ahamed, R and Oommen, TT and Nahaz, N and Tharakan, A and Rajesh, S and Augustine, P}, title = {Clinical outcomes and associated bacterial and fungal microbiota changes after high dose probiotic therapy for severe alcohol-associated hepatitis: An observational study.}, journal = {Medicine}, volume = {103}, number = {45}, pages = {e40429}, pmid = {39533632}, issn = {1536-5964}, mesh = {Humans ; *Hepatitis, Alcoholic/therapy ; Male ; *Probiotics/administration &amp; dosage/therapeutic use ; Middle Aged ; Female ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation/methods ; Adult ; Treatment Outcome ; Adrenal Cortex Hormones/administration &amp; dosage/therapeutic use ; Mycobiome ; Dysbiosis/therapy/microbiology ; }, abstract = {Alcohol-associated hepatitis (AH) is a critical condition with high mortality rates and is worsened by infections. Organ failure is strongly associated with intestinal dysbiosis. Emerging research suggests that gut microbiota modulation with probiotics can improve AH outcomes. This study investigated the clinical and microbiome effects of high-dose probiotic infusion (HDPI) compared with corticosteroid therapy (CST) and fecal microbiota transplantation (FMT) in severe AH. Patients with biopsy-proven severe-AH were enrolled from March 2019 to June 2020 and matched for age and disease severity. The patients received HDPI (n = 20), FMT (n = 16), or CST (n = 14). HDPI consists of a potent probiotic mix delivered via a nasoduodenal tube for 6 days. The primary outcome was survival at 90-days. Stool samples were subjected to 16S and 18S rRNA sequencing to assess significant bacterial and fungal taxa and their interactions at baseline and post treatment. At 90-days, survival rates were 55%, 64.3%, and 87.5% (HDPI, CST, respectively). HDPI did not beneficially impact bacterial alpha-diversity but significantly altered beta-diversity. Notably, the number of pathogenic bacteria, such as Bilophila and Roseburia increased. Fungal analysis revealed no significant changes in alpha diversity, but significant dissimilarities in beta diversity post-HDPI. New fungal genera such as Basidiomycota and Phragmoplastophyta have emerged, with significant deleterious expansion in fungal communities and damaging modifications between fungal-bacterial interactions. HDPI failed to outperform CST in improving the clinical outcomes of patients with severe AH. While HDPI influenced both bacterial and fungal microbiomes, it also led to the persistence of pathogenic communities. FMT showed superior survival outcomes, highlighting the urgent need for further controlled trials.}, }
@article {pmid39533343, year = {2024}, author = {Guo, X and Xu, J and Zhao, Y and Wang, J and Fu, T and Richard, ML and Sokol, H and Wang, M and Li, Y and Liu, Y and Wang, H and Wang, C and Wang, X and He, H and Wang, Y and Ma, B and Peng, S}, title = {Melatonin alleviates heat stress-induced spermatogenesis dysfunction in male dairy goats by regulating arachidonic acid metabolism mediated by remodeling the gut microbiota.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {233}, pmid = {39533343}, issn = {2049-2618}, support = {32072815//National Natural Science Foundation of China/ ; 2022YFD1300200//National Key Research and Development Program of China/ ; 2023-YBNY-140//General Project of the Key R &amp; D Plan of Shaanxi Province/ ; TG20221184//Ningbo Second Hormone Factory/ ; }, mesh = {Animals ; *Melatonin/pharmacology ; Male ; *Spermatogenesis/drug effects ; *Goats ; *Gastrointestinal Microbiome/drug effects ; *Testis/drug effects/metabolism ; Mice ; *Heat-Shock Response/drug effects ; *Arachidonic Acid/metabolism ; Spermatozoa/drug effects ; Oxidative Stress/drug effects ; }, abstract = {BACKGROUND: Heat stress (HS) commonly occurring in summer has gradually become a factor threatening the reproductive performance of male dairy goats by reducing their fecundity. Despite the melatonin is applied to relieve HS, it is still unclear whether melatonin protects against reproductive damage induced by HS in dairy goats and how it works. The purpose of the present study is to evaluate the role of melatonin in alleviating HS-induced spermatogenesis dysfunction in male dairy goats and further explore its mechanism.<br><br>RESULTS: HS impaired spermatogenesis, sperm formation in the testes, and sperm maturation in the epididymis of dairy goats, resulting in decreased sperm quality. Melatonin rescued the decrease of sperm quality induced by HS via decreasing inflammatory and oxidative stress levels in testicular tissue and enhancing intercellular barrier function within the testes. Amplicon-based microbiota analysis revealed that despite gut microbiota differences between melatonin-treated dairy goats and NC dairy goats to some extent, melatonin administration tends to return the gut microbiota of male dairy goats under HS to the levels of natural control dairy goats. To explore whether the protective role of melatonin in sperm quality is mediated by regulating gut microbiota, fecal microbiota of HS dairy goats with or without melatonin treatment were transferred to HS mice, respectively. We found HS mice that had received fecal bacteria of HS dairy goats experienced serious testicular injury and dyszoospermia, while this phenomenon was ameliorated in HS mice that had received fecal bacteria of dairy goats treated with melatonin, indicating melatonin alleviates HS-induced spermatogenic damage in a microbiota dependent manner. We further found that the testicular tissue of both HS dairy goats and mice transplanted with HS dairy goat feces produced large amounts of arachidonic acid (AA)-related metabolites, which were closely associated with semen quality. Consistently, supplementation with AA has been shown to elevate the levels of inflammation and oxidative stress in the testicular tissue of mice, disrupting intercellular connections and ultimately leading to spermatogenic disorders.<br><br>CONCLUSION: This study has revealed that melatonin can effectively alleviate spermatogenic disorders in dairy goats caused by HS. This beneficial effect was primarily achieved through the modulation of gut microbiota, which subsequently inhibited the excessive synthesis of AA in testicular tissue. These discoveries are of great significance for preventing or improving the decline in male livestock reproductive performance caused by HS, enhancing the reproductive efficiency of elite male breeds, and ultimately improving the production efficiency of animal husbandry. Video Abstract.}, }
@article {pmid39531305, year = {2024}, author = {Tursumetova, DR and Khan, Y and Tkacheva, LV and Rayevskii, KP}, title = {[The role and features of the gut microbiota in Alzheimer's disease.].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {37}, number = {4}, pages = {442-452}, pmid = {39531305}, issn = {1561-9125}, mesh = {*Alzheimer Disease/microbiology/therapy/physiopathology ; Humans ; *Gastrointestinal Microbiome/physiology ; *Probiotics/administration &amp; dosage/therapeutic use ; Fecal Microbiota Transplantation/methods ; Prebiotics/administration &amp; dosage ; Brain-Gut Axis/physiology ; Disease Progression ; }, abstract = {Alzheimer's disease causes gradual, persistent deterioration of cognitive function in the elderly, causing social and economic damage to society. Over the past decades, mankind has made significant progress in the study of Alzheimer's disease, but there are no methods to fully control the disease. The lack of effectiveness of existing treatment methods emphasizes the need to search for new approaches. The present review is devoted to the study of the latest data regarding the role of microbiota in the mechanisms of formation and progression of Alzheimer's disease, possible therapeutic ways to influence the processes of neurodegeneration through microbiota and taking into account identified relationships. The article considers the axis «gut microbiota-brain» as a link in the pathogenesis of neuroinflammation. New data on the influence of gut microbiota on neurodegenerative processes through metabolic, nervous, and immune mechanisms is analyzed. New data reveals correlations between microbiota specifics and the origin and/or progression of Alzheimer's disease, expanding the understanding of disease pathogenesis. The role of the oral microbiota in neurodegeneration processes is mentioned, emphasizing the diverse mechanisms of this disease. Available therapies for Alzheimer's disease are discussed, including probiotics and prebiotics, fecal microbiota transplantation, and dietary correction.}, }
@article {pmid39530534, year = {2024}, author = {Kao, D and Wong, K and Jijon, H and Moayyedi, P and Franz, R and McDougall, C and Hotte, N and Panaccione, R and Semlacher, E and Kroeker, KI and Peerani, F and MacDonald, KV and Xu, H and Narula, N and Turbide, C and Marshall, DA and Madsen, KL}, title = {Preliminary Results From a Multicenter, Randomized Trial Using Fecal Microbiota Transplantation to Induce Remission in Patients With Mild-to-Moderate Crohn's Disease.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000003196}, pmid = {39530534}, issn = {1572-0241}, support = {PJT 148913/CAPMC/CIHR/Canada ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) has shown promise at inducing remission in ulcerative colitis. This study is the first of its kind to evaluate the efficacy and safety of FMT at inducing remission in Crohn's disease (CD).<br><br>METHODS: This double-blind, placebo-controlled trial was conducted in 3 Canadian academic centers; randomized patients with mild-to-moderate CD received FMT or placebo. The first treatment was administered by colonoscopy followed by weekly oral capsules for 7 weeks. Primary end point was clinical and endoscopic remission at week 8. Secondary outcomes included clinical and endoscopic response, adverse events, and health-related quality of life using generic and disease-specific instruments.<br><br>RESULTS: From July 2017 to June 2021, 21 and 13 patients were randomized to FMT and placebo groups, respectively. The trial terminated early due to futility. At week 8, 0% (0/15) of patients in the FMT group versus 8.3% (1/11) in the placebo group reached the primary end point of combined clinical and endoscopic remission as per protocol analysis. There were no differences between the groups in clinical or endoscopic responses. One patient in each group had worsening of CD. Although both groups experienced statistically significant improvements in health-related quality of life, only the FMT group had a significant decrease in activity impairment. Although there were no significant changes in microbial diversity or composition, patients who achieved clinical response became more similar to their donors in stool microbial composition.<br><br>DISCUSSION: FMT was not effective at inducing clinical and endoscopic remission in CD using the FMT regimen in this study. Future studies may use other strategies to enhance treatment response, including longer intervention, antibiotic pretreatment, optimized donor-recipient pairing, and concomitant anti-inflammatory diet, and biologic or small molecule therapies.}, }
@article {pmid39528920, year = {2024}, author = {Laperrousaz, B and Levast, B and Fontaine, M and Nancey, S and Dechelotte, P and Doré, J and Lehert, P}, title = {Safety comparison of single-donor and pooled fecal microbiota transfer product preparation in ulcerative colitis: systematic review and meta-analysis.}, journal = {BMC gastroenterology}, volume = {24}, number = {1}, pages = {402}, pmid = {39528920}, issn = {1471-230X}, mesh = {*Colitis, Ulcerative/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Multiple studies have evaluated fecal microbiota transfer (FMT) in patients with ulcerative colitis (UC) using single-donor (SDN) and multidonor (MDN) products. Systematic review and meta-analysis were performed to compare the safety of SDN and MDN products.<br><br>METHODS: Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence to identify studies that compared FMT products manufactured using SDN or MDN strategies against control treatment in patients with UC. Fifteen controlled studies were selected for meta-analysis (11 randomized controlled trials and 4 controlled cohort trials). Safety of each treatment type was assessed using the counts of adverse events and serious adverse events using fixed- and random-effects models. Significance of the indirect difference between FMT preparations was assessed using a network approach. Benefit-risk ratios were calculated by multiplicative utility model, incorporating geometric mean of risk ratios (RRs) of efficacy and safety.<br><br>RESULTS: Safety data was collected for a total of 587 patients (193 exposed to SDN products, 114&#xa0;exposed to MDN products and 280 exposed to control treatment). The 12 studies showed similar overall safety event counts for MDN and SDN versus placebo (RRs: 0.90 and 1.09, respectively [P&#x2009;=&#x2009;0.206 and P&#x2009;=&#x2009;0.420, respectively]). Results indicated similar risk of safety events for MDN compared to SDN (RR: 0.83, P&#x2009;=&#x2009;0.159). Positive benefit-risk ratios were demonstrated for MDN and SDN versus placebo (RRs: 1.70 and 1.16, respectively [P&#x2009;=&#x2009;0.003 and P&#x2009;=&#x2009;0.173, respectively]). MDN had a greater benefit-risk ratio compared to SDN (RR: 1.46, P&#x2009;=&#x2009;0.072).<br><br>CONCLUSION: Similar safety profiles were observed for MDN and SDN strategies. Alongside previously described superior efficacy, treatment with MDN has greater benefit-risk ratio than SDN in patients with UC. Further development of MDN FMT treatment for UC should be considered.}, }
@article {pmid39526563, year = {2025}, author = {Tessier, MEM and Schraw, JM and Beer, S and Harpavat, S and Kyle Jensen, M and Magee, JC and Ng, V and Scheurer, ME and Taylor, SA and Shneider, BL}, title = {The association of human milk intake and outcomes in biliary atresia.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {80}, number = {1}, pages = {163-173}, pmid = {39526563}, issn = {1536-4801}, support = {U01 DK103140/DK/NIDDK NIH HHS/United States ; U01 DK062453/DK/NIDDK NIH HHS/United States ; U01DK103140//University of Utah/ ; U01 DK103135/DK/NIDDK NIH HHS/United States ; U01 DK062436/DK/NIDDK NIH HHS/United States ; U01DK062453//Children's Hospital Colorado/ ; U01DK103149//Texas Children's Hospital/ ; 5K23-DK119567//National Institute of Diabetes, Digestive and Kidney Diseases/ ; U01 DK062456/DK/NIDDK NIH HHS/United States ; U01DK103135//The Hospital for Sick Children/ ; U01 DK103149/DK/NIDDK NIH HHS/United States ; U24 DK062456/DK/NIDDK NIH HHS/United States ; U01 DK062497/DK/NIDDK NIH HHS/United States ; U01DK062456//The University of Michigan/ ; K23 DK119567/DK/NIDDK NIH HHS/United States ; U24DK062456//ChiLDReN's Scientific Data Coordinating Center, Ann Arbor, MI/ ; }, mesh = {Female ; Humans ; Infant ; Infant, Newborn ; Male ; *Biliary Atresia/surgery ; *Infant Formula ; *Milk, Human ; *Portoenterostomy, Hepatic/methods ; Treatment Outcome ; }, abstract = {OBJECTIVES: Human milk intake has many benefits which could influence outcomes in biliary atresia (BA). However, the role of human milk in BA has not been examined. We hypothesized that human milk intake would be associated with improved outcomes in BA.<br><br>METHODS: We assessed the impact of any human milk (AHM) as compared to formula only (FO) intake before Kasai portoenterostomy (KP) on outcomes in 447 infants with BA using the PROBE database (NCT00061828) post hoc. The primary outcome was clearance of jaundice (COJ&#x2009;=&#x2009;total bilirubin (TB)&#x2009;<&#x2009;2&#x2009;mg/dL by 3 months post-KP). Secondary outcomes included 2-year survival with native liver (SNL), bilirubin levels, cholangitis, ascites, and growth. We assessed the fecal microbiome (n&#x2009;=&#x2009;8) comparing AHM versus FO.<br><br>RESULTS: At baseline, 211 infants received AHM and 215 received FO. 53.9% of AHM and 50.5% of FO achieved COJ (p&#x2009;=&#x2009;NS). SNL was insignificantly increased in AHM (odds ratio&#x2009;=&#x2009;1.47, 95% confidence interval: 1.00-2.12, p&#x2009;=&#x2009;0.053). TB decreased in AHM from 4 weeks to 3 months post-KP [4.8-4.0&#x2009;mg/dL (p&#x2009;=&#x2009;0.01)] unlike the FO group (4.9-4.9&#x2009;mg/dL, p&#x2009;=&#x2009;0.4). At 3 months post-KP, AHM infants had greater weight gain (1.88&#x2009;&#xb1;&#x2009;0.66 vs. 1.57&#x2009;&#xb1;&#x2009;0.73&#x2009;kg, p&#x2009;<&#x2009;0.001) and mid-upper arm circumference (12.9&#x2009;&#xb1;&#x2009;1.4 vs. 12.2&#x2009;&#xb1;&#x2009;1.7&#x2009;cm, p&#x2009;<&#x2009;0.001). Other secondary outcomes were not different. Microbiome differences were seen between AHM and FO.<br><br>CONCLUSIONS: Human milk intake in infants with BA did not significantly improve COJ or SNL. However, growth parameters were improved, and TB 3 months post-KP was decreased. Thus, human milk intake should not be discouraged. Prospective studies with detailed assessment of human milk intake are needed.}, }
@article {pmid39523344, year = {2024}, author = {You, X and Yan, J and Herzog, J and Nobakhti, S and Campbell, R and Hoke, A and Hammamieh, R and Sartor, RB and Shefelbine, S and Kacena, MA and Chakraborty, N and Charles, JF}, title = {Bone loss with aging is independent of gut microbiome in mice.}, journal = {Bone research}, volume = {12}, number = {1}, pages = {65}, pmid = {39523344}, issn = {2095-4700}, support = {R01-AG046257//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; P30 AR075042/AR/NIAMS NIH HHS/United States ; R01 AG046257/AG/NIA NIH HHS/United States ; P30-AR070253//U.S. Department of Health &amp; Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/ ; 997397//Crohn's and Colitis Foundation (Crohn's &amp; Colitis Foundation)/ ; P40-OD010995//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; P30-DK034987//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Aging/physiology ; Male ; Mice ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Bone Resorption/microbiology ; Germ-Free Life ; }, abstract = {Emerging evidence suggests a significant role of gut microbiome in bone health. Aging is well recognized as a crucial factor influencing the gut microbiome. In this study, we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice. The bone phenotype of 24-month-old germ-free (GF) mice was indistinguishable compared to their littermates colonized by fecal transplant at 1-month-old. Moreover, bone loss from 3 to 24-month-old was comparable between GF and specific pathogen-free (SPF) mice. Thus, GF mice were not protected from age-related bone loss. 16S rRNA gene sequencing of fecal samples from 3-month and 24-month-old SPF males indicated an age-dependent microbial shift with an alteration in energy and nutrient metabolism potential. An integrative analysis of 16S predicted metagenome function and LC-MS fecal metabolome revealed an enrichment of protein and amino acid biosynthesis pathways in aged mice. Microbial S-adenosyl methionine metabolism was increased in the aged mice, which has previously been associated with the host aging process. Collectively, aging caused microbial taxonomic and functional alteration in mice. To demonstrate the functional importance of young and old microbiome to bone, we colonized GF mice with fecal microbiome from 3-month or 24-month-old SPF donor mice for 1 and 8 months. The effect of microbial colonization on bone phenotypes was independent of the microbiome donors' age. In conclusion, our study indicates age-related bone loss occurs independent of gut microbiome.}, }
@article {pmid39522895, year = {2024}, author = {Wan, J and Wang, F and Xiao, Y and Cheng, Y and Zheng, S and Jiang, Q and Tan, B and Li, X and Chen, J and Liao, S}, title = {Poria cocos polysaccharide alleviates dextran sulphate sodium-induced ulcerative colitis in mice by modulating intestinal inflammatory responses and microbial dysbiosis.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 2}, pages = {137450}, doi = {10.1016/j.ijbiomac.2024.137450}, pmid = {39522895}, issn = {1879-0003}, mesh = {Animals ; *Colitis, Ulcerative/chemically induced/drug therapy ; *Dextran Sulfate/adverse effects ; *Dysbiosis/chemically induced/drug therapy ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/pharmacology/chemistry ; *NF-kappa B/metabolism ; Wolfiporia/chemistry ; Male ; Disease Models, Animal ; Colon/drug effects/pathology/metabolism ; Mice, Inbred C57BL ; Inflammation/drug therapy ; }, abstract = {Poria cocos polysaccharide (PCP), one of the main active components of P. cocos, is extensively used worldwide and exhibits strong pharmacological effects. However, whether PCP can attenuate inflammatory bowel disease remains unclear. In this study, we assessed the effects of PCP supplementation on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice. We found that PCP supplementation mitigated UC symptoms in DSS-treated mice, as evidenced by reductions in body weight loss, colon length shortening and disease activity index score. Importantly, PCP supplementation enhanced colonic barrier integrity by increasing tight junction protein abundance and exerted anti-inflammatory effects by suppressing nuclear factor-κB (NF-κB) activation in DSS-treated mice. Furthermore, PCP supplementation reversed DSS-induced dysbiosis in colonic microbiota by increasing the colonic abundance of beneficial bacteria (e.g. Akkermansiaceae) and decreasing the colonic abundance of harmful bacteria (e.g. Erysipelotrichaceae) in DSS-treated mice. Although PCP supplementation failed to ameliorate DSS-induced UC in antibiotic-treated mice, faecal microbiota transplantation from PCP-administered mice ameliorated DSS-induced UC in antibiotic-treated mice. In summary, PCP alleviates UC in mice by attenuating intestinal inflammation via the inhibition of NF-κB activation and modulating the intestinal microbiota.}, }
@article {pmid39522254, year = {2024}, author = {Li, X and Khan, I and Han, R and Huang, G and Xia, W and Yin, L and Leong, WK and Su, L and Law, BY and Wong, VKW and Wu, Q and Guo, X and Hsiao, WLW}, title = {Gynostemma pentaphyllum saponins shield mice from peanut allergy by modulation of gut microbiota: A novel approach for peanut allergy management.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156101}, doi = {10.1016/j.phymed.2024.156101}, pmid = {39522254}, issn = {1618-095X}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/immunology ; *Gynostemma ; Mice, Inbred C57BL ; *Peanut Hypersensitivity/microbiology/prevention &amp; control ; Phytotherapy ; *Plant Extracts/pharmacology/therapeutic use ; *Saponins/pharmacology/therapeutic use ; Transcriptome/drug effects ; Drug Evaluation, Preclinical ; }, abstract = {BACKGROUND: Food allergies, particularly peanut (PN) allergies, are a growing concern, with fatal anaphylaxis incidents often reported. While palforzia is the sole FDA-approved drug for managing PN allergies, it is not universally effective.<br><br>PURPOSE: This study aimed to investigate the potential of Gynostemma pentaphyllum saponins (GpS) as a novel therapeutic agent for PN allergy through modulation of gut microbiota, addressing the limitations of current treatments.<br><br>METHODS: To elucidate the role of GpS on peanut allergy, we first built a PN-sensitized C57BL/6J model mice. Through comprehensive sequencing analysis, we identified Parabacteroides distasonis as a key bacterium triggering PN sensitization. Employing the same mouse model, GpS was evaluated for its effects on anaphylactic symptoms, serum immunoglobulin levels, and allergy-related biomarkers. 16S rRNA sequencing and transcriptomic analysis were applied to investigate the impact of GpS on the host's gut epithelium and microbiome.<br><br>RESULTS: GpS treatment effectively reduced anaphylactic symptoms in PN-sensitized mice, as shown by decreased IgG1, total IgE, and PN-specific IgE levels. It also modulated the immune response by suppressing proinflammatory cytokines (IL-1&#x3b2;, IFN-&#x3b3;, IL-21) and chemokines (CCL5, CCL12, CCL17, CCL22), while enhancing anti-inflammatory cytokines (IL-4, IL-10, IL-12, IL-13). Fecal microbial transplant from GpS-treated Model mice to PN-sensitized mice displayed anti-peanut allergy effects. Additionally, the administration of GpS-enhanced bacteria (Clostridium aldenese or Lactobacillus murinus), alleviated anaphylactic symptoms and reduced serum allergy markers in PN-sensitized mice.<br><br>CONCLUSION: To conclude, we revealed the intestinal environment, signaling molecules, mucosal cytokines, and commensal microbial profiles in the peanut-sensitized mouse model. We further presented evidence for the protective effect of GpS against PN allergen sensitization by downregulating a series of food-allergy-associated biomarkers and cytokines via the modulation of gut bacteria. More importantly, supported by both in vitro and in vivo experiments, we demonstrated that the protective effect of GpS against PN-allergy is through the enhancement of two commensal bacteria, Clostridium aldenese, and Lactobacillus murinus.}, }
@article {pmid39521596, year = {2024}, author = {Hurtado-Lorenzo, A and Swantek, JL}, title = {The landscape of new therapeutic opportunities for IBD.}, journal = {Advances in pharmacology (San Diego, Calif.)}, volume = {101}, number = {}, pages = {1-83}, doi = {10.1016/bs.apha.2024.10.011}, pmid = {39521596}, issn = {1557-8925}, mesh = {Humans ; *Inflammatory Bowel Diseases/drug therapy/therapy/immunology ; Animals ; Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, abstract = {This chapter presents an overview of the emerging strategies to address the unmet needs in the management of inflammatory bowel diseases (IBD). IBD poses significant challenges, as over half of patients experience disease progression despite interventions, leading to irreversible complications, and a substantial proportion do not respond to existing therapies, such as biologics. To overcome these limitations, we describe a diverse array of novel therapeutic approaches. In the area of immune homeostasis restoration, the focus is on targeting cytokine networks, leukocyte trafficking, novel immune pathways, and cell therapies involving regulatory T cells and mesenchymal stem cells (MSC). Recognizing the critical role of impaired intestinal barrier integrity in IBD, we highlight therapies aimed at restoring barrier function and promoting mucosal healing, such as those targeting cell proliferation, tight junctions, and lipid mediators. Addressing the challenges posed by fibrosis and fistulas, we describe emerging targets for reversing fibrosis like kinase and cytokine inhibitors and nuclear receptor agonists, as well as the potential of MSC for fistulas. The restoration of a healthy gut microbiome, through strategies like fecal microbiota transplantation, rationally defined bacterial consortia, and targeted antimicrobials, is also highlighted. We also describe innovative approaches to gut-targeted drug delivery to enhance efficacy and minimize side effects. Reinforcing these advancements is the critical role of precision medicine, which emphasizes the use of multiomics analysis for the discovery of biomarkers to enable personalized IBD care. Overall, the emerging landscape of therapeutic opportunities for IBD holds great potential to surpass the therapeutic ceiling of current treatments.}, }
@article {pmid39521225, year = {2024}, author = {Yang, X and Zhang, X and Ma, Y and Li, S and Wang, Q and Hong, JS and Yu, G and Qi, B and Wang, J and Liu, C and Shang, Q and Wu, X and Zhao, J}, title = {Fucoidan ameliorates rotenone-induced Parkinsonism in mice by regulating the microbiota-gut-brain axis.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 2}, pages = {137373}, doi = {10.1016/j.ijbiomac.2024.137373}, pmid = {39521225}, issn = {1879-0003}, mesh = {Animals ; *Polysaccharides/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Rotenone ; Male ; *Brain-Gut Axis/drug effects ; Neuroprotective Agents/pharmacology ; Disease Models, Animal ; Parkinsonian Disorders/drug therapy/chemically induced ; Brain/drug effects/metabolism ; Signal Transduction/drug effects ; Fecal Microbiota Transplantation ; Oxidative Stress/drug effects ; Mice, Inbred C57BL ; }, abstract = {Microbiota-gut-brain axis, the bidirectional relationship between the gut microbiota and the brain, has been increasingly appreciated in the pathogenesis of Parkinson's disease (PD). Fucoidan, a sulphate-rich polysaccharide, has been shown to be neuroprotective by reducing oxidative stress in PD models. However, the role of microbiota-gut-brain axis in the neuroprotective activity of fucoidan has not been revealed. In this study, the therapeutic effects of fucoidan and involvement of microbiota-gut-brain axis in rotenone (ROT)-induced PD were investigated. The results showed that fucoidan gavage attenuated neuroinflammation, dopamine neuronal damage and motor dysfunction in ROT-induced PD mice. In addition, fucoidan treatment ameliorated gut dysfunction, intestinal inflammation and disruption of the intestinal barrier in PD mice. Fucoidan also affected the composition of gut microbiota in PD mice, indicated particularly by decreased abundance of Akkermansia muciniphila and Lactobacillus johnsonii and increased abundance of Lactobacillus murinus. Mechanistic studies showed that fecal microbiota transplantation (FMT) from the fucoidan-treated mice and probiotic Lactobacillus murinus supplement are as potent as fucoidan treatment in attenuating peripheral and central inflammation and ameliorating dopamine neuronal damage, which might be attributed to the downregulation of LPS/TLR4/NF-κB signaling pathway. Our study suggests that fucoidan might be potential candidates for the treatment of PD.}, }
@article {pmid39519488, year = {2024}, author = {Pinto, C and Carrasco-Loncharic, T and González-Mienert, E and de Solminihac, J and Gálvez-Jirón, F and Cifuentes, F and Pino-Lagos, K}, title = {IL-33 Induces a Switch in Intestinal Metabolites Revealing the Tryptophan Pathway as a Target for Inducing Allograft Survival.}, journal = {Nutrients}, volume = {16}, number = {21}, pages = {}, pmid = {39519488}, issn = {2072-6643}, support = {1210654//Fondo Nacional de Desarrollo Cient&#xed;fico y Tecnol&#xf3;gico (Fondecyt)/ ; }, mesh = {Animals ; *Tryptophan/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Graft Survival/drug effects ; *Interleukin-33/metabolism ; *Skin Transplantation ; *T-Lymphocytes, Regulatory/metabolism ; Mice ; *Mice, Inbred C57BL ; Intestines/drug effects ; Allografts ; Mice, Inbred BALB C ; Male ; Kynurenic Acid/metabolism ; Dysbiosis ; }, abstract = {BACKGROUND: IL-33, a pleiotropic cytokine, has been associated with a plethora of immune-related processes, both inflammatory and anti-inflammatory. T regulatory (Treg) cells, the main leukocyte population involved in immune tolerance, can be induced by the administration of IL-33, the local microbiota, and its metabolites. Here, we demonstrate that IL-33 drastically induces the production of intestinal metabolites involved on tryptophan (Trp) metabolism.<br><br>METHODS: na&#xef;ve mice were treated with IL-33 for 4 days and leukocyte populations were analyzed by flow cytometry, and feces were processed for microbiota and intestinal metabolites studies. Using a murine skin transplantation model, the effect of Kynurenic acid (KA) on allograft survival was tested.<br><br>RESULTS: Under homeostatic conditions, animals treated with IL-33 showed an increment in Treg cell frequencies. Intestinal bacterial abundance analysis indicates that IL-33 provokes dysbiosis, demonstrated by a reduction in Enterobacteria and an increment in Lactobacillus genera. Furthermore, metabolomics analysis showed a dramatic IL-33 effect on the abundance of intestinal metabolites related to amino acid synthesis pathways, highlighting molecules linked to Trp metabolism, such as kynurenic acid (KA), 5-Hydroxyindoleacetic acid (5-HIAA), and 6-Hydroxynicotinic acid (6-HNA), which was supported by an enhanced expression of Ido and Kat mRNA in MLN cells, which are two enzymes involved on KA synthesis. Interestingly, animals receiving KA in drinking water and subjected to skin transplantation showed allograft acceptance, which is associated with an increment in Treg cell frequencies.<br><br>CONCLUSIONS: Our study reveals a new property for IL-33 as a modulator of the intestinal microbiota and metabolites, especially those involved with Trp metabolism. In addition, we demonstrate that KA favors Tregs in vivo, positively affecting skin transplantation survival.}, }
@article {pmid39519055, year = {2024}, author = {Misiąg, P and Molik, K and Kisielewska, M and Typek, P and Skowron, I and Karwowska, A and Kuźnicki, J and Wojno, A and Ekiert, M and Choromańska, A}, title = {Amelanotic Melanoma-Biochemical and Molecular Induction Pathways.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39519055}, issn = {1422-0067}, mesh = {Humans ; *Melanoma, Amelanotic/metabolism/genetics/pathology ; Proto-Oncogene Proteins B-raf/genetics/metabolism/antagonists &amp; inhibitors ; Biomarkers, Tumor/metabolism ; Proto-Oncogene Proteins c-kit/genetics/metabolism/antagonists &amp; inhibitors ; Skin Neoplasms/metabolism/genetics/pathology/therapy ; Melanins/metabolism/biosynthesis ; Signal Transduction ; }, abstract = {Amelanotic melanoma (AM) is a subtype of hypomelanotic or completely amelanotic melanoma. AM is a rare subtype of melanoma that exhibits a higher recurrence rate and aggressiveness as well as worse surveillance than typical melanoma. AM shows a dysregulation of melanin production, cell cycle control, and apoptosis pathways. Knowing these pathways has an application in medicine due to targeted therapies based on the inhibiting elements of the abovementioned pathways. Therefore, we summarized and discussed AM biochemical and molecular induction pathways and personalized medicine approaches, clinical management, and future directions due to the fact that AM is relatively rare. AM is commonly misdiagnosed. Hence, the role of biomarkers is becoming significant. Nonetheless, there is a shortage of biomarkers specific to AM. BRAF, NRAS, and c-KIT genes are the main targets of therapy. However, the role of BRAF and KIT in AM varied among studies. BRAF inhibitors combined with MAK inhibitors demonstrate better results. Immune checkpoint inhibitors targeting CTLA-4 combined with a programmed death receptor 1 (PD-1) show better outcomes than separately. Fecal microbiota transplantation may overcome resistance to immune checkpoint therapy of AM. Immune-modulatory vaccines against indoleamine 2,3-dioxygenase (IDO) and PD ligand (PD-L1) combined with nivolumab may be efficient in melanoma treatment.}, }
@article {pmid39518717, year = {2024}, author = {Brusnic, O and Onisor, D and Boicean, A and Hasegan, A and Ichim, C and Guzun, A and Chicea, R and Todor, SB and Vintila, BI and Anderco, P and Porr, C and Dura, H and Fleaca, SR and Cristian, AN}, title = {Fecal Microbiota Transplantation: Insights into Colon Carcinogenesis and Immune Regulation.}, journal = {Journal of clinical medicine}, volume = {13}, number = {21}, pages = {}, pmid = {39518717}, issn = {2077-0383}, abstract = {Colorectal cancer (CRC) constitutes a significant global health challenge, with recent studies underscoring the pivotal role of the gut microbiome in its pathogenesis and progression. Fecal microbiota transplantation (FMT) has emerged as a compelling therapeutic approach, offering the potential to modulate microbial composition and optimize treatment outcomes. Research suggests that specific bacterial strains are closely linked to CRC, influencing both its clinical management and therapeutic interventions. Moreover, the gut microbiome's impact on immunotherapy responsiveness heralds new avenues for personalized medicine. Despite the promise of FMT, safety concerns, particularly in immunocompromised individuals, remain a critical issue. Clinical outcomes vary widely, influenced by genetic predispositions and the specific transplantation methodologies employed. Additionally, rigorous donor selection and screening protocols are paramount to minimize risks and maximize therapeutic efficacy. The current body of literature advocates for the establishment of standardized protocols and further clinical trials to substantiate FMT's role in CRC management. As our understanding of the microbiome deepens, FMT is poised to become a cornerstone in CRC treatment, underscoring the imperative for continued research and clinical validation.}, }
@article {pmid39515099, year = {2024}, author = {Yu, ZQ and Du, HX and Gao, S and Liang, CZ}, title = {Eriocalyxin B ameliorated experimental autoimmune prostatitis via modulation of macrophage polarization through gut microbiota-mediated vitamin D3 alteration.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156191}, doi = {10.1016/j.phymed.2024.156191}, pmid = {39515099}, issn = {1618-095X}, mesh = {Animals ; Male ; *Gastrointestinal Microbiome/drug effects ; *Macrophages/drug effects ; Mice ; *Prostatitis/drug therapy ; *Cholecalciferol/pharmacology ; *Autoimmune Diseases/drug therapy ; *Disease Models, Animal ; Feces/microbiology ; Mice, Inbred C57BL ; Diterpenes/pharmacology ; Anti-Inflammatory Agents/pharmacology ; Cytokines/metabolism ; }, abstract = {BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a often heterogeneous condition in urology. Accumulating evidence suggests that the autoimmune response against prostate antigens is related to CP/CPPS. The gut microbiota may be a possible cause of a number of autoimmune diseases. Eriocalyxin B (EriB) is used as an anti-inflammatory treatment for autoimmune disorders. The underlying mechanism of fecal metabolome involved in CP/CPPS treatment by EriB remains unclear.<br><br>METHODS: The experimental autoimmune prostatitis (EAP) mouse model was generated by subcutaneous immunization. Macrophages, inflammatory cytokines, intestinal microbiota, and fecal metabolome of the mice were analyzed. The alteration of the fecal metabolome was investigated in detail in EriB-treated EAP mice and confirmed by in vitro experiments.<br><br>RESULTS: EriB ameliorated significantly decreased prostate inflammation in EAP mice and promoted macrophage phenotype polarizing from M1 to M2. The gut microbiome was altered, and intestinal barrier damage was improved by EriB treatment. Furthermore, the enrichment of vitamin digestion and absorption pathways in the fecal metabolome revealed that vitamin D3 was altered by EriB. In vitro experiments confirmed that macrophage polarization from M1 to M2 was promoted by vitamin D3. Finally, fecal transplantation from EriB-treated mice markedly reduced inflammatory indicators and the macrophage M1/M2 ratio in pseudogerm-free EAP mice. In our study, the immune state of macrophage regulated by gut microbiota-mediated vitamin D3 alteration was first time revealed in EAP treatment.<br><br>CONCLUSIONS: EriB ameliorated in mice with EAP, the gut microbiota mediates vitamin D3 alterations to modulate macrophage phenotype polarizing from M1 to M2.}, }
@article {pmid39515036, year = {2024}, author = {Sun, B and Hu, C and Li, J and Yang, Z and Chen, L}, title = {Interaction between young fecal transplantation and perfluorobutanesulfonate endocrine disrupting toxicity in aged recipients: An estrobolome perspective.}, journal = {Environment international}, volume = {193}, number = {}, pages = {109133}, doi = {10.1016/j.envint.2024.109133}, pmid = {39515036}, issn = {1873-6750}, mesh = {Animals ; *Fluorocarbons ; *Endocrine Disruptors/toxicity ; *Feces/chemistry/microbiology ; *Zebrafish ; Water Pollutants, Chemical/toxicity ; Liver/drug effects ; Sulfonic Acids ; Estrone ; Estrogens ; Estradiol ; }, abstract = {Transplanting young feces into the aged was found to effectively counteract the endocrine disrupting effects of perfluorobutanesulfonate (PFBS) pollutant, showing promise in the maintenance of healthy aging. However, the interactive mechanisms between young fecal transplantation and PFBS endocrine disruption during aging remain unclear. In this follow-up study, aged zebrafish were administered young donor feces and then exposed to environmentally relevant concentrations of PFBS (0 and 100 μg/L). Alterations in the holistic estrobolome along gut-liver axis were investigated. The results showed that PFBS singular exposure significantly increased blood estradiol concentration in the aged, inducing an estrogenic activity. Concentrations of other estrogen forms, including estrone and estriol, were also disrupted by PFBS. Interestingly, young fecal transplant effectively mitigated the estrogenic toxicity of PFBS and largely restored estrogen equilibrium. After PFBS exposure, the transcriptions of estrogen metabolic genes were consistently upregulated in aged livers, causing the accumulation of 2-methoxyestradiol-3-methylether metabolite. In contrast, aged livers coexposed to young fecal transplant and PFBS enhanced the glucuronidation process, successfully facilitating the elimination and detoxification of estrogen metabolites. In aged gut, PFBS exposure inhibited β-glucuronidase enzyme activity, implying the suppression of estrogen deconjugation and recycle. However, in the combined group, β-glucuronidase activity was significantly stimulated, thus reestablishing estrobolome dynamics. Overall, current findings provide mechanistic insights into the antagonistic interaction between young fecal transplant and PFBS on reproductive endocrinology. Gut microbiota manipulation appears appealing to maintain healthy aging progression albeit the interruption of environmental xenobiotics.}, }
@article {pmid39513042, year = {2024}, author = {Park, KJ and Gao, Y}, title = {Gut-brain axis and neurodegeneration: mechanisms and therapeutic potentials.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1481390}, pmid = {39513042}, issn = {1662-4548}, abstract = {This paper reviews the effects of gut microbiota in regulating neurodegenerative diseases through controlling gut-brain axis. Specific microbial populations and their metabolites (short-chain fatty acids and tryptophan derivatives) regulate neuroinflammation, neurogenesis and neural barrier integrity. We then discuss ways by which these insights lead to possible interventions - probiotics, prebiotics, dietary modification, and fecal microbiota transplantation (FMT). We also describe what epidemiological and clinical studies have related certain microbiota profiles with the courses of neurodegenerative diseases and how these impact the establishment of microbiome-based diagnostics and individualized treatment options. We aim to guide microbial ecology research on this key link to neurodegenerative disorders and also to highlight collaborative approaches to manage neurological health by targeting microbiome-related factors.}, }
@article {pmid39510500, year = {2025}, author = {Scull, CE and Hu, Y and Jennings, S and Wang, G}, title = {Normalization of Cystic Fibrosis Immune System Reverses Intestinal Neutrophilic Inflammation and Significantly Improves the Survival of Cystic Fibrosis Mice.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {19}, number = {2}, pages = {101424}, pmid = {39510500}, issn = {2352-345X}, mesh = {Animals ; *Cystic Fibrosis/immunology/mortality/therapy/complications/pathology ; *Neutrophils/immunology/metabolism ; Nitric Oxide Synthase Type II/metabolism/antagonists &amp; inhibitors ; Mice ; Disease Models, Animal ; Nitric Oxide/metabolism ; Inflammation/immunology ; Bone Marrow Transplantation ; Intestinal Mucosa/immunology/pathology ; *Intestines/immunology/pathology ; Male ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND &amp; AIMS: Cystic fibrosis (CF) is an autosomal recessive genetic disorder, affecting multiple organ systems. CF intestinal disease develops early, manifesting as intestinal bacterial overgrowth/dysbiosis, neutrophilic inflammation, and obstruction. As unresolvable infection and inflammation reflect host immune deficiency, we sought to determine if the CF-affected immune system plays any significant role in CF intestinal disease pathogenesis.<br><br>METHODS: CF and sibling wild-type (WT) mice underwent reciprocal bone marrow transplantation. After immune reconstitution, their mortality, intestinal transit, fecal inflammatory markers, and mucosal immune cell composition were assessed. Moreover, reciprocal neutrophil transfusion was conducted to determine if neutrophil function affects intestinal movement. Furthermore, expression of induced nitric oxide synthase (iNOS) and production of nitric oxide (NO) in CF and WT neutrophils were compared. Lastly, specific iNOS inhibitor 1400W was tested to prevent CF intestinal obstruction.<br><br>RESULTS: Immune restoration in CF mice reversed the intestinal neutrophilic inflammation, improved the intestinal dysmotility, and rescued the mice from mortality. Transfusion of WT neutrophils into CF mice ameliorated the retarded bowel movement. CF neutrophils expressed significantly more iNOS and produced significantly more NO. Pharmaceutical blocking of iNOS significantly improved intestinal transit and survival of CF mice.<br><br>CONCLUSIONS: CF immune defect plays a critical role in CF intestinal disease development. Activation of iNOS in inflammatory cells produces excessive NO, slows the bowel movement, and facilitates intestinal paralysis and obstruction in CF. Thus, normalization of the CF immune system may offer a novel therapy to treat CF intestinal disease.}, }
@article {pmid39510376, year = {2025}, author = {Huang, Y and You, Y and Wang, W and Chen, YH and Zhang, H and Li, QP and Liu, L and Tong, K and Sun, N and Hao, JR and Gao, C}, title = {Adenosine regulates depressive behavior in mice with chronic social defeat stress through gut microbiota.}, journal = {Neuropharmacology}, volume = {262}, number = {}, pages = {110209}, doi = {10.1016/j.neuropharm.2024.110209}, pmid = {39510376}, issn = {1873-7064}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology/drug effects ; *Adenosine/metabolism ; Male ; Mice ; *Stress, Psychological/metabolism ; *Fecal Microbiota Transplantation ; *Social Defeat ; *Depression/therapy/metabolism ; Dysbiosis ; Humans ; Mice, Inbred C57BL ; Depressive Disorder, Major/metabolism/therapy ; Probiotics/administration &amp; dosage/pharmacology ; Female ; }, abstract = {Major depressive disorder (MDD) is recognized as the most prevalent affective disorder worldwide. Metagenomic studies increasingly support a critical role for dysbiosis of gut microbiota in the development of depression. Previous studies have demonstrated that adenosine alleviates gut dysbiosis, suggesting that elevating adenosine levels could be a novel intervention for MDD; however, the mechanisms underlying this effect remain unclear. This study utilized 16S rRNA gene sequencing, fecal microbiota transplantation (FMT) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to test the hypothesis that increased adenosine alleviates depressive behaviors in male mice subjected to chronic social defeat stress (CSDS) through alterations to gut microbiota. The data showed that depression-susceptible (SUS) mice exhibited gut dysbiosis, and FMT from SUS mice increased depression-like behaviors in healthy recipients. In SUS mice, adenosine supplementation ameliorated both depression-like behaviors and abnormalities in gut microbiota, and co-administration of probiotics and adenosine not only mitigated depression-like behaviors but also enhanced gut barrier integrity. By including 83 depressed adolescents and 67 healthy controls, this study found that the level of short-chain fatty acids (SCFAs) in the depression group was reduced, this finding parallels reductions seen in SUS mice and in recipient mice after FMT from SUS donors. Conversely, supplementation with either adenosine or probiotics led increased SCFAs concentrations in the serum of SUS mice. These findings suggest that adenosine may alleviate depression-like behaviors in CSDS mice by modulating the gut microbiota. This effect is likely associated with increased serum SCFAs, metabolites produced by the gut microbiota, following adenosine supplementation. This article is part of the Special Issue on "Personality Disorders".}, }
@article {pmid39510013, year = {2024}, author = {Yang, D and Lv, G and Wu, Y and Guo, W and Wang, Y and Hu, J and Li, N and Zheng, F and Dai, Y and Pi, Z and Yue, H}, title = {Licorice-regulated gut-joint axis for alleviating collagen-induced rheumatoid arthritis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156203}, doi = {10.1016/j.phymed.2024.156203}, pmid = {39510013}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Arthritis, Rheumatoid/drug therapy ; *Arthritis, Experimental/drug therapy ; *Glycyrrhiza/chemistry ; Rats ; *Th17 Cells/drug effects ; Joints/drug effects ; T-Lymphocytes, Regulatory/drug effects ; Male ; Anti-Inflammatory Agents/pharmacology ; Plant Extracts/pharmacology ; Amine Oxidase (Copper-Containing)/metabolism ; Colon/drug effects/metabolism ; RNA, Ribosomal, 16S ; Collagen Type II/metabolism ; Lipopolysaccharides ; Cattle ; Tight Junction Proteins/metabolism ; Intestinal Mucosa/drug effects/metabolism ; }, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is partially affected by the integrity of the intestinal barrier. Licorice (GC), a medicinal and food-related herb, exhibits potent anti-inflammatory activity; however, studies on its mechanisms of action in RA are limited.<br><br>METHOD: Using a bovine type-II collagen-induced arthritis rat model, this study examined how GC influences the gut-joint axis to decrease RA. The Th17/Treg cell ratios in the blood, colon, and joints were also measured. Metabolomics and 16S rRNA sequencing were applied to explore the effects of variations in gut flora and metabolites.<br><br>RESULTS: The arthropathological slices, inflammation markers, and joint inflammation index scores in the GC treatment group significantly differed from those in the CIA group. Studies on the effect of GC on the gut-joint axis showed changes in the levels of lipopolysaccharide and diamine oxidase, both directly associated with intestinal permeability. ZO-1, occludin, and claudin-1, three intestinal tight-junction proteins, may express themselves more when exposed to GC. By maintaining an appropriate Th17/Treg cell ratio in the blood, colon, and joints, GC may reduce impaired to the intestinal barrier. An imbalance in the intestinal microenvironment, caused by modifications in gut flora and endogenous substances, can damage the intestinal barrier. GC may modify the relative abundances of Papillibacter, Clostridium, Eubacterium, Helicobacter, Provotella, and Barnesiella during RA treatment by repairing the intestinal barrier. The metabolic differences were mainly related to primary bile acid biosynthesis, pyrimidine metabolism, steroid biosynthesis, biotin metabolism, and sphingolipid metabolism. A fecal microbiota transplantation experiment confirmed the involvement of the gut microbiota and its metabolites in GC-mediated RA therapy.<br><br>CONCLUSION: The results demonstrated that GC repairs the intestinal barrier and adjusts the gut-joint axis to manage immunological imbalance in RA.}, }
@article {pmid39509684, year = {2025}, author = {L'Huillier, JC and Guo, WA}, title = {The always evolving diagnosis and management of Clostridioides difficile colitis: What you need to know.}, journal = {The journal of trauma and acute care surgery}, volume = {98}, number = {3}, pages = {357-367}, doi = {10.1097/TA.0000000000004474}, pmid = {39509684}, issn = {2163-0763}, mesh = {Humans ; *Clostridioides difficile/isolation &amp; purification ; *Clostridium Infections/diagnosis/therapy ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Colectomy/methods ; *Colitis/diagnosis/therapy/microbiology ; Broadly Neutralizing Antibodies ; Antibodies, Monoclonal ; }, abstract = {The diagnosis, pharmacologic management, and surgical options for Clostridioides difficile infection (CDI) are rapidly evolving, which presents a challenge for the busy surgeon to remain up to date on the latest clinical guidelines. This review provides an evidence-based practical guide for CDI management tailored to the needs of surgeons and surgical intensivists. Historically, the diagnosis of CDI relied on slow cell culture cytotoxicity neutralization assays, but now, the rapidly resulting nucleic acid amplification tests and enzyme immunoassays have become mainstream. In terms of antibiotic therapy, metronidazole and oral vancomycin were the main "workhorse" antibiotics in the early 2000s, but large randomized controlled trials have now demonstrated that fidaxomicin produces superior results. Regarding surgical intervention, total abdominal colectomy was once the only procedure of choice; however, diverting loop ileostomy with colonic lavage is emerging as a viable alternative. Finally, novel adjuncts such as fecal microbiota transplantation and targeted therapy against toxin B (bezlotoxumab) are playing an increasingly important role in the management of CDI.}, }
@article {pmid39507519, year = {2024}, author = {Claassen-Weitz, S and du Toit, E and Gardner-Lubbe, S and Kullin, B and Bellairs, G and Hilton, C and Chicken, A and Welp, K and Livingstone, H and Brink, A}, title = {Knowledge and perceptions of South African blood donors towards biobanking and stool donation.}, journal = {Southern African journal of infectious diseases}, volume = {39}, number = {1}, pages = {645}, pmid = {39507519}, issn = {2313-1810}, abstract = {BACKGROUND: The complexity of contexts and varied purposes for which biome donation are requested are unknown in South Africa.<br><br>OBJECTIVES: The aim of this study was to provide strategic data towards actualisation of whether a stool donor bank may be established as a collaborative between Western Cape Blood Services (WCBS) and the University of Cape Town (UCT).<br><br>METHOD: We designed a cross-sectional, questionnaire-based survey to determine willingness of WCBS blood donors to donate stool specimens for microbiome biobanking. The study was conducted between 01 June 2022 and 01 July 2022 at three WCBS donation centres in Cape Town, South Africa. Anonymous blood donors who met the inclusion criteria were enrolled. Anonymised demographic and interview data were analysed statistically.<br><br>RESULTS: Analysis of responses from 209/231 blood donors demonstrated in a logistic regression model that compensation (p < 0.001) and 'societal benefit outweighs inconvenience' beliefs (p = 7.751e-05) were covariates significantly associated with willingness to donate stool. Age was borderline significant at a 5% level (p = 0.0556). Most willing stool donors indicated that donating stool samples would not affect blood donations (140/157, 90%). Factors decreasing willingness to donate were stool collection being unpleasant or embarrassing.<br><br>CONCLUSION: The survey provides strategic data for the establishment of a stool bank and provided an understanding of the underlying determinants regarding becoming potential donors.<br><br>CONTRIBUTION: This is the first report on the perspectives of potential participants in donating samples towards a stool microbiome biobank in South Africa, a necessity for faecal microbiota transplantation (FMT).}, }
@article {pmid39508236, year = {2024}, author = {Shen, H and Zhang, C and Zhang, Q and Lv, Q and Liu, H and Yuan, H and Wang, C and Meng, F and Guo, Y and Pei, J and Yu, C and Tie, J and Chen, X and Yu, H and Zhang, G and Wang, X}, title = {Gut microbiota modulates depressive-like behaviors induced by chronic ethanol exposure through short-chain fatty acids.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {290}, pmid = {39508236}, issn = {1742-2094}, support = {82271931//National Natural Science Foundation of China/ ; 82101979//National Natural Science Foundation of China/ ; 2022-MS-220//Natural Science Foundation of Liaoning Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; *Ethanol/toxicity/administration &amp; dosage/pharmacology ; *Depression/chemically induced/metabolism ; *Fatty Acids, Volatile/metabolism ; Male ; *Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Anxiety/chemically induced ; Central Nervous System Depressants/pharmacology/toxicity ; }, abstract = {BACKGROUND: Chronic ethanol exposure (CEE) is recognized as an important risk factor for depression, and the gut-brain axis has emerged as a key mechanism underlying chronic ethanol exposure-induced anxiety and depression-like behaviors. Short-chain fatty acids (SCFAs), which are the key metabolites generated by gut microbiota from insoluble dietary fiber, exert protective roles on the central nervous system, including the reduction of neuroinflammation. However, the link between gut microbial disturbances caused by chronic ethanol exposure, production of SCFAs, and anxiety and depression-like behaviors remains unclear.<br><br>METHODS: Initially, a 90-day chronic ethanol exposure model was established, followed by fecal microbiota transplantation model, which was supplemented with SCFAs via gavage. Anxiety and depression-like behaviors were determined by open field test, forced swim test, and elevated plus-maze. Serum and intestinal SCFAs levels were quantified using GC-MS. Changes in related indicators, including the intestinal barrier, intestinal inflammation, neuroinflammation, neurotrophy, and nerve damage, were detected using Western blotting, immunofluorescence, and Nissl staining.<br><br>RESULTS: Chronic ethanol exposure disrupted with gut microbial homeostasis, reduced the production of SCFAs, and led to anxiety and depression-like behaviors. Recipient mice transplanted with fecal microbiota that had been affected by chronic ethanol exposure exhibited impaired intestinal structure and function, low levels of SCFAs, intestinal inflammation, activation of neuroinflammation, a compromised blood-brain barrier, neurotrophic defects, alterations in the GABA system, anxiety and depression-like behaviors. Notably, the negative effects observed in these recipient mice were significantly alleviated through the supplementation of SCFAs.<br><br>CONCLUSION: SCFAs not only mitigate damage to intestinal structure and function but also alleviate various lesions in the central nervous system, such as neuroinflammation, and reduce anxiety and depression-like behaviors, which were triggered by transplantation with fecal microbiota that had been affected by chronic ethanol exposure, adding more support that SCFAs serve as a bridge between the gut and the brain.}, }
@article {pmid39502702, year = {2024}, author = {Han, YJ and Kim, S and Shin, H and Kim, HW and Park, JD}, title = {Protective effect of gut microbiota restored by fecal microbiota transplantation in a sepsis model in juvenile mice.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1451356}, pmid = {39502702}, issn = {1664-3224}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Sepsis/therapy/microbiology/immunology ; Mice ; *Disease Models, Animal ; Male ; Cytokines/metabolism/blood ; Anti-Bacterial Agents/therapeutic use ; Dysbiosis/therapy ; Feces/microbiology ; Mice, Inbred C57BL ; }, abstract = {INTRODUCTION: Restoring a balanced, healthy gut microbiota through fecal microbiota transplantation (FMT) has the potential to be a treatment option for sepsis, despite the current lack of evidence. This study aimed to investigate the effect of FMT on sepsis in relation to the gut microbiota through a sepsis model in juvenile mice.<br><br>METHODS: Three-week-old male mice were divided into three groups: the antibiotic treatment (ABX), ABX-FMT, and control groups. The ABX and ABX-FMT groups received antibiotics for seven days. FMT was performed through oral gavage in the ABX-FMT group over the subsequent seven days. On day 14, all mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Blood cytokine levels and the composition of fecal microbiota were analyzed, and survival was monitored for seven days post-CLP.<br><br>RESULTS: Initially, the fecal microbiota was predominantly composed of the phyla Bacteroidetes and Firmicutes. After antibiotic intake, an extreme predominance of the class Bacilli emerged. FMT successfully restored antibiotic-induced fecal dysbiosis. After CLP, the phylum Bacteroidetes became extremely dominant in the ABX-FMT and control groups. Alpha diversity of the microbiota decreased after antibiotic intake, was restored after FMT, and decreased again following CLP. In the ABX group, the concentrations of interleukin-1&#x3b2; (IL-1&#x3b2;), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-&#x3b1;, and C-X-C motif chemokine ligand 1 increased more rapidly and to a higher degree compared to other groups. The survival rate in the ABX group was significantly lower (20.0%) compared to other groups (85.7%).<br><br>CONCLUSION: FMT-induced microbiota restoration demonstrated a protective effect against sepsis. This study uniquely validates the effectiveness of FMT in a juvenile mouse sepsis model, offering potential implications for clinical research in critically ill children.}, }
@article {pmid39502523, year = {2024}, author = {Anouti, A and Kerr, TA and Mitchell, MC and Cotter, TG}, title = {Advances in the management of alcohol-associated liver disease.}, journal = {Gastroenterology report}, volume = {12}, number = {}, pages = {goae097}, pmid = {39502523}, issn = {2052-0034}, abstract = {Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g. heavy drinking, metabolic syndromes) and non-modifiable risk factors (e.g. genetic predispositions) is crucial for effective disease management. Alcohol use assessment and treatment, by using both behavioral therapy and pharmacotherapeutic modalities, nutrition support, and optimization of liver disease modifiers, form the cornerstone of management. Advances in medical therapies, such as fecal microbiota transplantation and novel agents such as IL-22, are being explored for their therapeutic potential. A unifying theme in ALD care is the need for a personalized approach to management, accounting for the spectrum of the disease and individual patient characteristics, to tailor interventions effectively. Finally, it is essential to address the challenges to effective ALD treatment, including socioeconomic, logistical, and stigma-related barriers, to improve patient outcomes. This review discusses the current knowledge on ALD, including epidemiology, pathophysiology, risk factors, and management strategies, highlighting the critical role of integrated care models.}, }
@article {pmid39500537, year = {2024}, author = {Slizovskiy, IB and Bonin, N and Bravo, JE and Ferm, PM and Singer, J and Boucher, C and Noyes, NR}, title = {Factors impacting target-enriched long-read sequencing of resistomes and mobilomes.}, journal = {Genome research}, volume = {34}, number = {11}, pages = {2048-2060}, pmid = {39500537}, issn = {1549-5469}, support = {R01 AI141810/AI/NIAID NIH HHS/United States ; R01 AI173928/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Animals ; *Metagenomics/methods ; Cattle ; Feces/microbiology ; Drug Resistance, Bacterial/genetics ; High-Throughput Nucleotide Sequencing/methods ; Gastrointestinal Microbiome/genetics ; Interspersed Repetitive Sequences ; Sequence Analysis, DNA/methods ; Metagenome ; Bacteria/genetics/drug effects/classification ; Soil Microbiology ; }, abstract = {We investigated the efficiency of target-enriched long-read sequencing (TELSeq) for detecting antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) within complex matrices. We aimed to overcome limitations associated with traditional antimicrobial resistance (AMR) detection methods, including short-read shotgun metagenomics, which can lack sensitivity, specificity, and the ability to provide detailed genomic context. By combining biotinylated probe-based enrichment with long-read sequencing, we facilitated the amplification and sequencing of ARGs, eliminating the need for bioinformatic reconstruction. Our experimental design included replicates of human fecal microbiota transplant material, bovine feces, pristine prairie soil, and a mock human gut microbial community, allowing us to examine variables including genomic DNA input and probe set composition. Our findings demonstrated that TELSeq markedly improves the detection rates of ARGs and MGEs compared to traditional sequencing methods, underlining its potential for accurate AMR monitoring. A key insight from our research is the importance of incorporating mobilome profiles to better predict the transferability of ARGs within microbial communities, prompting a recommendation for the use of combined ARG-MGE probe sets for future studies. We also reveal limitations for ARG detection from low-input workflows, and describe the next steps for ongoing protocol refinement to minimize technical variability and expand utility in clinical and public health settings. This effort is part of our broader commitment to advancing methodologies that address the global challenge of AMR.}, }
@article {pmid39500027, year = {2024}, author = {Hua, Y and Zhou, C and Fan, R and Benazzouz, S and Shen, J and Xiao, R and Ma, W}, title = {Altered intestinal microbiota induced by high-fat diets affect cognition differently in mice.}, journal = {Nutrition research (New York, N.Y.)}, volume = {132}, number = {}, pages = {67-84}, doi = {10.1016/j.nutres.2024.09.019}, pmid = {39500027}, issn = {1879-0739}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Male ; *Mice, Inbred C57BL ; *Cognition/drug effects ; *Hippocampus ; *Feces/microbiology ; *Fecal Microbiota Transplantation ; Fatty Acids, Omega-3/pharmacology ; Mice ; Fatty Acids, Omega-6/pharmacology ; Cognitive Dysfunction ; Neurons ; Obesity/microbiology ; RNA, Ribosomal, 16S ; }, abstract = {The role of the gut microbiota in the association between high-fat diet and cognition is not clear. We hypothesized that a high-fat diet may influence cognition by altering the intestinal microbiota. Fecal microbiota isolated from male C57BL/6J mice feeding on various high-fat diets and a control basic diet were transplanted to antibiotic-treated recipient mice. The measurement of weight and plasma lipids, novel object recognition test, 16S rRNA gene sequencing of feces, and hematoxylin-eosin staining of the hippocampal cornu ammonis 1 and cornu ammonis 3 areas were performed for all mice. Compared with those in the control and n-3 polyunsaturated fatty acid (n-3 PUFA) groups, donor obese mice fed with diets high in long-chain saturated fatty acids, n-6 polyunsaturated fatty acids (n-6 PUFAs), and trans fatty acids exhibited significant cognitive impairment (all P < .05). There were fewer neurons in the hippocampal area in the n-6 PUFA group than in the n-3 PUFA group (P < .05). Similar effect on cognition and neurons in hippocampal area in corresponding recipient mice were revealed after fecal microbiota transplantation. In addition, the composition of intestinal microbiota differed among recipient mice after fecal microbiota transplantation from donor mice. According to these results, it was concluded that diets rich in long-chain saturated fatty acids, n-6 PUFAs, and trans fatty acids may lead to cognitive impairment by damaging the structure of the hippocampus through influencing the intestinal microbiota in mice, whereas a diet high in n-3 PUFAs may exhibit a beneficial effect.}, }
@article {pmid39499189, year = {2024}, author = {Ghani, R and Chrysostomou, D and Roberts, LA and Pandiaraja, M and Marchesi, JR and Mullish, BH}, title = {Faecal (or intestinal) microbiota transplant: a tool for repairing the gut microbiome.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2423026}, pmid = {39499189}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; *Clostridium Infections/therapy/microbiology ; Animals ; Feces/microbiology ; Clostridioides difficile/physiology ; Treatment Outcome ; Donor Selection ; }, abstract = {Faecal/intestinal microbiota transplant (FMT/IMT) is an efficacious treatment option for recurrent Clostridioides difficile infection, which has prompted substantial interest in FMT's potential role in the management of a much broader range of diseases associated with the gut microbiome. Despite its promise, the success rates of FMT in these other settings have been variable. This review critically evaluates the current evidence on the impact of clinical, biological, and procedural factors upon the therapeutic efficacy of FMT, and identifies areas that remain nebulous. Due to some of these factors, the optimal therapeutic approach remains unclear; for example, the preferred timing of FMT administration in a heavily antibiotic-exposed hematopoietic cell transplant recipient is not standardized, with arguments that can be made in alternate directions. We explore how these factors may impact upon more informed selection of donors, potential matching of donors to recipients, and aspects of clinical care of FMT recipients. This includes consideration of how gut microbiome composition and functionality may strategically inform donor selection criteria. Furthermore, we review how the most productive advances within the FMT space are those where clinical and translational outcomes are assessed together, and where this model has been used productively in recent years to better understand the contribution of the gut microbiome to human disease, and start the process toward development of more targeted microbiome therapeutics.}, }
@article {pmid39495286, year = {2024}, author = {Zhang, H and Zhou, W and Gao, P and Li, Z and Li, C and Li, J and Bian, J and Gong, L and He, C and Han, L and Wang, M}, title = {Ellagic Acid Protects against Alcohol-Related Liver Disease by Modulating the Hepatic Circadian Rhythm Signaling through the Gut Microbiota-NPAS2 Axis.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {45}, pages = {25103-25117}, doi = {10.1021/acs.jafc.4c06992}, pmid = {39495286}, issn = {1520-5118}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Circadian Rhythm ; Animals ; *Basic Helix-Loop-Helix Transcription Factors/metabolism/genetics ; *Liver/metabolism/drug effects ; *Liver Diseases, Alcoholic/metabolism/prevention &amp; control/microbiology/drug therapy ; Mice ; Male ; Humans ; *Ellagic Acid/pharmacology ; *Mice, Inbred C57BL ; Signal Transduction/drug effects ; Nerve Tissue Proteins/genetics/metabolism ; Bacteria/classification/genetics/metabolism/isolation &amp; purification/drug effects ; Protective Agents/pharmacology/administration &amp; dosage ; }, abstract = {Alcohol-related liver disease (ALD) encompasses a spectrum of hepatic disorders resulting from alcohol abuse, which constitutes the predominant etiology of morbidity and mortality associated with hepatic pathologies globally. Excessive alcohol consumption disrupts the integrity of the intestinal barrier and perturbs the balance of gut microbiota, thereby facilitating the progression of ALD. Ellagic acid (EA) has been extensively reported to be an effective intervention for alleviating liver symptoms. However, the target molecules of EA in improving ALD and its underlying mechanism remain elusive. First, our study indicates that EA ameliorated ALD through the hepatic circadian rhythm signaling by up-regulating neuronal PAS domain protein 2 (NPAS2). Furthermore, analysis of the intestinal microbiome showed that EA significantly enhanced the abundance of beneficial bacteria, which was positively correlated with NPAS2 expression and negatively correlated with liver injury. Finally, antibiotic treatment and fecal microbiota transplantation (FMT) experiments established a causal relationship between the reshaped microbiota and NPAS2 in the amelioration of ALD. In summary, our study demonstrates novel evidence that EA attenuated ALD by modulating the hepatic circadian rhythm signaling pathway via the gut microbiota-NPAS2 axis, providing valuable insights for EA and microbiome-targeted interventions against ALD.}, }
@article {pmid39494101, year = {2024}, author = {Singh, AK and Durairajan, SSK and Iyaswamy, A and Williams, LL}, title = {Elucidating the role of gut microbiota dysbiosis in hyperuricemia and gout: Insights and therapeutic strategies.}, journal = {World journal of gastroenterology}, volume = {30}, number = {40}, pages = {4404-4410}, pmid = {39494101}, issn = {2219-2840}, mesh = {*Dysbiosis ; Humans ; *Gout/microbiology/therapy/complications ; *Gastrointestinal Microbiome/physiology ; *Hyperuricemia/microbiology/blood/therapy/diagnosis ; *Uric Acid/blood/metabolism ; *Probiotics/therapeutic use/administration &amp; dosage ; *Prebiotics/administration &amp; dosage ; Gout Suppressants/therapeutic use ; }, abstract = {Hyperuricemia (HUA) is a condition associated with a high concentration of uric acid (UA) in the bloodstream and can cause gout and chronic kidney disease. The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people. This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder. Some studies have suggested that changes in the composition, diversity, and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis. Therefore, we discussed how the gut microbiota contributes to HUA through purine metabolism, UA excretion, and intestinal inflammatory responses. We examined specific changes in the composition of the gut microbiota associated with gout and HUA, highlighting key bacterial taxa and the metabolic pathways involved. Additionally, we discussed the effect of conventional gout treatments on the gut microbiota composition, along with emerging therapeutic approaches that target the gut microbiome, such as the use of probiotics and prebiotics. We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.}, }
@article {pmid39493843, year = {2024}, author = {Duan, X and Nie, Y and Xie, X and Zhang, Q and Zhu, C and Zhu, H and Chen, R and Xu, J and Zhang, J and Yang, C and Yu, Q and Cai, K and Wang, Y and Tian, W}, title = {Sex differences and testosterone interfere with the structure of the gut microbiota through the bile acid signaling pathway.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1421608}, pmid = {39493843}, issn = {1664-302X}, abstract = {BACKGROUND: The gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism.<br><br>METHODS: 16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues.<br><br>RESULTS: The composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically SHP, FXR, CYP7A1, and ASBT) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway.<br><br>CONCLUSION: Sex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway.}, }
@article {pmid39493719, year = {2024}, author = {Wang, L and Yu, L and Liu, Z and Che, C and Wang, Y and Zhao, Y and Zhu, M and Yang, G and Cao, A}, title = {FMT intervention decreases urine 5-HIAA levels: a randomized double-blind controlled study.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1411089}, pmid = {39493719}, issn = {2296-858X}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is often linked to gastrointestinal issues and altered serotonin metabolism. Emerging evidence suggests gut microbiota influence both, with fecal microbiota transplantation (FMT) offering a potential therapeutic approach. However, its impact on serotonin metabolism and ASD symptoms is not well understood. In this study, we aimed to evaluate the clinical effects of FMT and examine changes in specific urinary metabolites in children with ASD.<br><br>METHODS: A randomized double-blind controlled trial was performed to evaluate the clinical effects of FMT on GI and ASD-related symptoms. Gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and the ASD-related symptoms were assessed using the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and Social Responsiveness Scale (SRS) scores. Urinary metabolites were analyzed by homogeneous enzyme immunoassay using commercially available kits.<br><br>RESULTS: Significant improvements in GI and core ASD symptoms were observed following FMT intervention. The average GSRS scores decreased from 30.17 (before) to 19 (after; p&#x2009;<&#x2009;0.0001), CARS scores decreased from 36.22 to 33.33 (p&#x2009;<&#x2009;0.0001), SRS scores decreased from 151.17 to 137.5 (p&#x2009;=&#x2009;0.0002), and the ABC scores decreased 76.39 to 53.17 (p&#x2009;<&#x2009;0.0001) in the FMT group. However, in the placebo group, GSRS, CARS, and SRS scores showed no significant changes, while ABC scores decreased from 72 to 58.75 (p&#x2009;=&#x2009;0.034). The FMT group also showed a significant reduction in urinary 5-hydroxyindoleacetic acid (5-HIAA) levels from 8.6 to 7.32&#x2009;mg/L (p&#x2009;=&#x2009;0.022), while other metabolites showed no significant changes.<br><br>CONCLUSION: FMT is a safe and effective treatment for improving GI and core symptoms in children with ASD, with 5-HIAA showing potential as a urinary biomarker for treatment response.}, }
@article {pmid39492827, year = {2024}, author = {Jiang, L and Fan, JG}, title = {Gut microbiota in gastrointestinal diseases: Insights and therapeutic strategies.}, journal = {World journal of gastroenterology}, volume = {30}, number = {39}, pages = {4329-4332}, pmid = {39492827}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; Inflammatory Bowel Diseases/microbiology/therapy ; Hypertension, Portal/microbiology/therapy/diagnosis/etiology ; Liver/microbiology/metabolism ; Gastrointestinal Diseases/microbiology/therapy ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Considering the bidirectional crosstalk along the gut-liver axis, gut-derived microorganisms and metabolites can be released into the liver, potentially leading to liver injury. In this editorial, we comment on several studies published in the recent issue of the World Journal of Gastroenterology. We focus specifically on the roles of gut microbiota in selected gastrointestinal (GI) diseases that are prevalent, such as inflammatory bowel disease, metabolic dysfunction-associated steatotic liver disease, and hepatitis B virus-related portal hypertension. Over the past few decades, findings from both preclinical and clinical studies have indicated an association between compositional and metabolic changes in the gut microbiota and the pathogenesis of the aforementioned GI disorders. However, studies elucidating the mechanisms underlying the host-microbiota interactions remain limited. The purpose of this editorial is to summarize current findings and provide insights regarding the context-specific roles of gut microbiota. Ultimately, the discovery of microbiome-based biomarkers may facilitate disease diagnosis and the development of personalized medicine.}, }
@article {pmid39492826, year = {2024}, author = {Kong, MW and Yu, Y and Wang, P and Wan, Y and Gao, Y and Zhang, CX}, title = {Advances in the research of intestinal fungi in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {39}, pages = {4318-4323}, pmid = {39492826}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/immunology ; Humans ; *Gastrointestinal Microbiome ; Animals ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; *Fungi/pathogenicity ; *Disease Models, Animal ; Intestines/microbiology ; Mice ; Adipose Tissue/microbiology ; Mesentery/microbiology ; }, abstract = {This article reviews of the original research published by Wu et al in the World Journal of Gastroenterology, delving into the pivotal role of the gut microbiota in the pathogenesis of Crohn's disease (CD). Insights were gained from fecal microbiota transplantation (FMT) in mouse models, revealing the intricate interplay between the gut microbiota, mesenteric adipose tissue (MAT), and creeping fat. The study uncovered the characteristics of inflammation and fibrosis in the MAT and intestinal tissues of patients with CD; moreover, through the FMT mouse model, it observed the impact of samples from healthy patients and those with CD on symptoms. The pathogenesis of CD is complex, and its etiology remains unclear; however, it is widely believed that gut microbiota dysbiosis plays a significant role. Recently, with the development and application of next-generation sequencing technology, research on the role of fungi in the pathogenesis and chronicity of CD has deepened. This editorial serves as a supplement to the research by Wu et al who discussed advances related to the study of fungi in CD.}, }
@article {pmid39491642, year = {2025}, author = {Shimokawa, C}, title = {The gut microbiome-helminth-immune axis in autoimmune diseases.}, journal = {Parasitology international}, volume = {104}, number = {}, pages = {102985}, doi = {10.1016/j.parint.2024.102985}, pmid = {39491642}, issn = {1873-0329}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Autoimmune Diseases/immunology/microbiology ; Animals ; *Helminths/immunology/physiology ; Diabetes Mellitus, Type 1/immunology/microbiology ; Helminthiasis/immunology/parasitology ; }, abstract = {The global prevalence of autoimmune diseases has surged in recent decades. Consequently, environmental triggers have emerged as crucial contributors to autoimmune diseases, equally relevant to classical risk factors, such as genetic polymorphisms, infections, and smoking. Sequencing-based approaches have demonstrated distinct gut microbiota compositions in individuals with autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus (T1D), and systemic lupus erythematosus, compared to healthy controls. Furthermore, fecal microbiota transplantation and microbial inoculation experiments have supported the hypothesis that alterations in the gut microbiota can influence autoimmune responses and disease outcomes. Herein, we propose that intestinal helminths may serve as a critical factor in inducing alterations in the gut microbiota. The concept of helminth-mediated suppression of autoimmune diseases in humans is supported by substantial evidence, aligning with the long-standing "hygiene hypothesis." This review focused on T1D to explore the interactions between parasites, gut microbiota, and the immune system-a topic that remains a black box within this intricate triangular relationship.}, }
@article {pmid39491609, year = {2025}, author = {Chen, D and Xie, J and Chen, X and Qin, B and Kong, D and Luo, J}, title = {Fecal microbiota transplantation alleviates neuronal Apoptosis, necroptosis and reactive microglia activation after ischemic stroke.}, journal = {Neuroscience}, volume = {564}, number = {}, pages = {299-305}, doi = {10.1016/j.neuroscience.2024.10.053}, pmid = {39491609}, issn = {1873-7544}, mesh = {Animals ; *Microglia/metabolism ; Male ; *Rats, Sprague-Dawley ; *Apoptosis/physiology ; *Necroptosis/physiology ; *Fecal Microbiota Transplantation/methods ; *Neurons/metabolism/pathology ; *Ischemic Stroke/therapy/pathology/metabolism ; Rats ; Infarction, Middle Cerebral Artery/therapy/pathology ; Brain/metabolism/pathology ; Brain Ischemia/therapy/pathology/microbiology/metabolism ; }, abstract = {OBJECTIVE: This study aims to delve into the mechanisms underlying the improvement of neurological function in rats with ischemic stroke through fecal microbiota transplantation.<br><br>METHODS: A total of fifty male Sprague-Dawley rats were categorized into four groups: Sham, MCAO, MCAO+vehicle and FMT. We assessed behavioral and pathological alterations in the rats using modified neurological function scoring and TTC staining.Additionally, Western blot and immunofluorescence were used to detect the expression levels of Apoptotic and Necroptosis markers in neurons of ischemic brain tissue, and immunofluorescence was used to analyze the degree of activation of microglia.<br><br>RESULTS: FMT group exhibited a decline in neurological function score compared to the MCAO and MCAO&#xa0;+&#xa0;vehicle group, accompanied by a reduction in infarct volume (P&#xa0;<&#xa0;0.05). Relative to the SHAM group, the MCAO group displayed a significant increase in the expression levels of necroptosis-related proteins Phospho-RIP1, Phospho-RIP3, Phospho-MLKL, apoptotic proteins Bax and Cleaved caspase-3, and the iNOS positive microglia in ischemic brain tissue, while Bcl-2 expression was notably decreased (P&#xa0;<&#xa0;0.05).Conversely, compared to the MCAO&#xa0;+&#xa0;vehicle group, the FMT group showed decreased expression levels of Phospho-RIP1, Phospho-RIP3, Phospho-MLKL, Bax, Cleaved caspase-3, and iNOS-positive microglia, while the expression of Bcl-2 was increased.<br><br>CONCLUSION: Fecal microbiota transplantation offers a promising approach to improving neurological function in rats with ischemic stroke by inhibiting neuronal apoptosis, necroptosis, and the polarization of inflammatory microglial cells.}, }
@article {pmid39491142, year = {2023}, author = {Zhao, T and Lv, J and Peng, M and Mi, J and Zhang, S and Liu, J and Chen, T and Sun, Z and Niu, R}, title = {Fecal microbiota transplantation and short-chain fatty acids improve learning and memory in fluorosis mice by BDNF-PI3K/AKT pathway.}, journal = {Chemico-biological interactions}, volume = {}, number = {}, pages = {110786}, doi = {10.1016/j.cbi.2023.110786}, pmid = {39491142}, issn = {1872-7786}, abstract = {Fluoride, an environmental toxicant, not only arouses intestinal microbiota dysbiosis, but also causes neuronal apoptosis and a decline in learning and memory ability. The purpose of this study was to explore whether fecal microbiota transplantation (FMT) from healthy mice and bacteria-derived metabolites short-chain fatty acids (SCFAs) supplement protect against fluoride-induced learning and memory impairment. Results showed that FMT reversed the elevated percentage of working memory errors (WME) and reference memory errors (RME) in fluorosis mice during the eight-arm maze test. Nissl and TUNEL staining presented that fluoride led to a decreased proportion of Nissl bodies area in the hippocampal CA3 region and an increased apoptotic ratio of nerve cells in CA1, CA3 and DG areas, whereas FMT alleviated those pathological damages. Moreover, the expressions of mRNA in hippocampal BDNF, PDK1, AKT, Bcl-2, and Bcl-xL were downregulated in mice exposed to fluoride, but the levels of PI3K, Bax, Bak, and Caspase-7 mRNA were upregulated. NaF treatment had an increase in PI3K and Caspase-3 protein levels and reduced the expressions of these four proteins, including BDNF, p-PI3K, AKT and p-AKT. By contrast, FMT enhanced the expression of BDNF and thus activated the PI3K/AKT pathway. Besides, the 16S rRNA sequencing revealed that fluoride caused a reduction in certain SCFA producers in the colon as evidenced by a decline in Erysipelatoclostridiaceae, and a downward trend in Akkermansia, Blautia and Alistipes. However, the disordered gut microbiome was restored via frequent FMT. Of note, SCFAs administration also increased BDNF levels and regulated its downstream pathways, which contributed to cell survival and learning and memory function recovery. In conclusion, FMT and SCFAs may activate the BDNF-PI3K/AKT pathway to play an anti-apoptotic role and ultimately improve learning and memory deficits in fluorosis mice.}, }
@article {pmid39490563, year = {2024}, author = {Wu, J and Zhang, R and Yin, Z and Chen, X and Mao, R and Zheng, X and Yuan, M and Li, H and Lu, Y and Liu, S and Gao, X and Sun, Q}, title = {Gut microbiota-driven metabolic alterations reveal the distinct pathogenicity of chemotherapy-induced cachexia in gastric cancer.}, journal = {Pharmacological research}, volume = {209}, number = {}, pages = {107476}, doi = {10.1016/j.phrs.2024.107476}, pmid = {39490563}, issn = {1096-1186}, mesh = {Aged ; Animals ; Female ; Humans ; Male ; Mice ; Middle Aged ; Antineoplastic Agents/adverse effects ; *Cachexia/microbiology/metabolism/chemically induced ; *Gastrointestinal Microbiome/drug effects ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; *Stomach Neoplasms/drug therapy/microbiology ; }, abstract = {Cachexia affects approximately 50-80 % of advanced cancer patients, particularly those with gastric cancer (GC). Therefore, early detection of cachexia is essential to prevent its progression. Targeting the gut microbiota may be a promising approach for preventing and treating cachexia in patients with GC. Chemotherapy significantly reduced gut microbiota diversity in GC patients. Specifically, the abundance of bacterial genera such as Bacteroides, Streptococcus, and Prevotella was increased in the gut of patients postchemotherapy, which was closely associated with the development of cachexia. Serum metabolic analysis revealed a strong link between specific microbes and metabolite in patients with chemotherapy-induced GC cachexia. We further constructed a random forest model based on the top 6 genera in terms of abundance for the prediction of chemotherapy-related GC cachexia development; this model had an area under the receiver operating characteristic curve (AUC) of 93.5 % [95 % confidence interval (CI), 86.6 %-100 %], with a specificity and accuracy above 75 %. Additionally, we identified Enterotoxin Bacteroides fragilis (ETBF) as a key factor in chemotherapy-induced GC cachexia. In an in vivo GC model, the colonization of ETBF in the intestines of mice significantly accelerated the muscle and adipose tissue consumption induced by chemotherapy, resulting in cachexia symptoms. Furthermore, ETBF damaged the intestinal mucosal barrier by disrupting cell connections and attracting M1 macrophages, which advances GC cachexia. In conclusion, our findings indicate that gut microbiota imbalance is crucial in GC cachexia development, suggesting potential biomarkers for early diagnosis. Clinical trial registration: http://www.chictr.org.cn, Identification No: ChiCTR2200064547.}, }
@article {pmid39489477, year = {2024}, author = {Chen, W and Liu, Y and Pu, J and Gui, S and Wang, D and Zhong, X and Tao, W and Chen, X and Chen, X and Chen, Y and Zhao, L and Wu, Q and Chen, X and Zhang, Y and Xie, A and Xie, P}, title = {Comparative transcriptional analyses of the striatum in the chronic social defeat stress model in C57BL/6J male mice and the gut microbiota-dysbiosis model in Kumming mice.}, journal = {Neuroscience}, volume = {562}, number = {}, pages = {217-226}, doi = {10.1016/j.neuroscience.2024.10.057}, pmid = {39489477}, issn = {1873-7544}, mesh = {Animals ; Male ; *Mice, Inbred C57BL ; *Stress, Psychological/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; *Social Defeat ; *Corpus Striatum/metabolism ; Mice ; *Disease Models, Animal ; *Dysbiosis/genetics ; Depression/microbiology ; Transcriptome ; Fecal Microbiota Transplantation ; }, abstract = {Depression is a complex disorder with multiple contributing factors, and chronic stress has previously been recognized as a major causative factor, while gut microbes have also been found to be involved in depression recently. However, gene expression in depression models with different etiologies is unclear. Here, we compared the transcriptomes of the striatum in chronic social defeat stress (CSDS) model of C57BL/6J male mice and fecal microbiota transplant (FMT) model of Kumming male mice. We found that the proportion of shared differentially expressed genes (DEGs) between the two models was only 24 %. The specific DEGs of FMT model were enriched in immune and inflammatory, and are associated with changes in vascular and ciliated ependymal cells. The specific DEGs of CSDS model were enriched in neuron and synapse. The results of network analysis suggested the expression patterns and biological function of depressive-like behaviors-related modules in the two models are different. Further, the alternative splicing events of CSDS are more than FMT. Our results suggested models of depression induced by different etiologies differ significantly in gene expression and biological function. Our study also suggested us to pay attention to the characteristics of models of depression of different etiologies and provided a more comprehensive understanding of the heterogeneity of depression.}, }
@article {pmid39487198, year = {2024}, author = {Chatthanathon, P and Leelahavanichkul, A and Cheibchalard, T and Wilantho, A and Hirankarn, N and Somboonna, N}, title = {Comparative time-series analyses of gut microbiome profiles in genetically and chemically induced lupus-prone mice and the impacts of fecal transplantation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {26371}, pmid = {39487198}, issn = {2045-2322}, support = {CU_FRB65_hea(68)_131_23_61//Thailand Science Research and Innovation Fund Chulalongkorn University/ ; }, mesh = {Animals ; *Lupus Erythematosus, Systemic/microbiology/immunology/genetics ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Mice ; *Receptors, IgG/genetics ; *Dysbiosis/microbiology ; *Disease Models, Animal ; Female ; Feces/microbiology ; Mice, Knockout ; Terpenes ; Mice, Inbred C57BL ; }, abstract = {Although the association between gut dysbiosis (imbalance of the microbiota) in systemic lupus erythematosus (SLE) is well-known, the simultaneous exploration in gut dysbiosis in fecal and different intestinal sections before and after lupus onset (at 2, 4, 6, 8, and 10 months old) resulting from the loss of inhibitory Fc gamma receptor IIb (FcGIIb) and pristane induction have never been conducted. Anti-dsDNA (an important lupus autoantibody) and proteinuria developed as early as 6 months old in both models, with higher levels in FcGRIIb deficient (FcGRIIb-/-) mice. Compared to the healthy control at 2 and 4 months, the lupus mice (both FcGRRIIb-/- and pristane) and healthy mice at 6 months old demonstrated an alteration as indicated by the Shannon alpha diversity index, highlighting influences of lupus- and age-induced dysbiosis, respectively. Non-metric multidimensional scaling (NMDS) revealed that the fecal microbiota of FcGRIIb-/- mice were distinct from the age-matched healthy control at all timepoints (at 6 month, p < 0.05), while pristane mice showed divergence at only some timepoints. Analyses of different intestinal sections revealed similarity among microbiota in the cecum, colon, and feces, contrasting with those in the small intestines (duodenum, jejunum, and ileum). Subtle differences were found between FcGRIIb-/- and pristane mice in feces and the intestinal sections as assessed by several analyses, for examples, the similar or dissimilar distances (NMDS), the neighbor-joining clustering, and the potential metabolisms (KEGG pathway analysis). Due to the differences between the gut microbiota (feces and intestinal sections) in the lupus mice and the healthy control, rebalancing of the microbiota using rectal administration of feces from the healthy control (fecal transplantation; FMT) to 7-month-old FcGIIb-/- mice (the established lupus; positive anti-dsDNA and proteinuria) was performed. In comparison to FcGRIIb-/- mice without FMT, FMT mice (more effect on the female than the male mice) showed the lower anti-dsDNA levels with similar fecal microbiome diversity (16s DNA gene copy number) and microbiota patterns to the healthy control. In conclusion, gut microbiota (feces and intestinal sections) of lupus mice (FcGRIIb-/- and pristane) diverged from the control as early as 4-6 months old, correlating with lupus characteristics (anti-dsDNA and proteinuria). The different gut microbiota in FcGRIIb-/- and pristane suggested a possible different gut microbiota in lupus with various molecular causes. Furthermore, FMT appeared to mitigate gut dysbiosis and reduce anti-dsDNA, supporting the benefit of the rebalancing gut microbiota in lupus, with more studies are warranted.}, }
@article {pmid39484201, year = {2024}, author = {Cheng, X and Ren, C and Mei, X and Jiang, Y and Zhou, Y}, title = {Gut microbiota and irritable bowel syndrome: status and prospect.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1429133}, pmid = {39484201}, issn = {2296-858X}, abstract = {Irritable bowel syndrome (IBS) is a very common gastrointestinal disease that, although not as aggressive as tumors, affects patients' quality of life in different ways. The cause of IBS is still unclear, but more and more studies have shown that the characteristics of the gut microbiota, such as diversity, abundance, and composition, are altered in patients with IBS, compared to the healthy population, which confirms that the gut microbiota plays a crucial role in the development of IBS. This paper aims to identify the commonalities by reviewing a large body of literature. Changes in the characteristics of gut microbiota in patients with different types of IBS are discussed, relevant mechanisms are described, and the treatment modalities of gut microbiota in IBS are summarized. Although there are more clinical trials that have made good progress, more standardized, more generalized, larger-scale, multi-omics clinical studies are what is missing. Overall, gut microbiota plays a crucial role in the development of IBS, and there is even more potential for treating IBS by modulating gut microbiota.}, }
@article {pmid39484168, year = {2024}, author = {Duo, H and Yang, Y and Zhang, G and Chen, Y and Cao, Y and Luo, L and Pan, H and Ye, Q}, title = {Comparative effectiveness of treatments for recurrent Clostridioides difficile infection: a network meta-analysis of randomized controlled trials.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1430724}, pmid = {39484168}, issn = {1663-9812}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infectious diarrhea. A major clinical challenge is recurrent CDI (rCDI) without effective standard drug-based therapy. Additionally, a comprehensive comparison of various therapy effectiveness in rCDI patients is still under investigation.<br><br>METHODS: A Bayesian network meta-analysis (NMA) of randomized control trials up to March 2024 was performed to investigate the efficacy of rCDI interventions.<br><br>RESULTS: Seventeen trials were included, comprising 4,148 CDI patients with ten interventions, including fecal microbiota transplantation (FMT) by lower gastrointestinal (LGI), FMT by upper gastrointestinal (UGI), Autologous FMT (AFMT), vancomycin + FMT, vancomycin, placebo, fidaxomicin, Vowst (SER109), Rebyota (RBX2660), and monoclonal antibody. NMA showed that FMT by LGI had the highest efficacy in treating rCDIs with an odds ratio (95% confidence interval) of 32.33 (4.03, 248.69) compared with placebo. FMT by UGI also showed high efficacy, whereas the efficacy comparison between FMT by LGI and UGI was not statistically significant (ORs) (95% CI), 1.72 (0.65, 5.21). The rankogram and surface under the cumulative ranking curve (SUCRA) also showed FMT by LGI ranked at the top and FMT by UGI ranked second in the curative effect.<br><br>CONCLUSION: NMA demonstrates FMT's significant efficacy in rCDI management, regardless of administration route (lower or upper gastrointestinal). Despite its significant benefits, FMT's safety is a concern due to the lack of standardized FDAcompliant manufacturing and oversight. Microbiota-based therapies also exhibit potential. However, limited research mandates further clinical exploration. Antibiotics, in contrast, display comparatively reduced efficacy in rCDI, potentially linked to disruptions in native gut microflora balance.<br><br>SYSTEMATIC REVIEW: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=368435, Identifier CRD42022368435.}, }
@article {pmid39483608, year = {2024}, author = {Aslam, MR and Perala, A and Wishart, AV and Hamouda, RK and Elsaady, E and Khan, S}, title = {Therapeutic Potential of Fecal Microbiota Transplantation in Type 2 Diabetes Mellitus: A Systematic Review.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e70642}, pmid = {39483608}, issn = {2168-8184}, abstract = {Diabetes mellitus is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. It can cause various complications, which result in significant morbidity and mortality. There are multiple treatment options available to combat this disease; however, despite this, the incidence of type 2 diabetes mellitus is continuously increasing. Some promising results have shown that dysbiosis has a role in the pathogenesis of type 2 diabetes mellitus and fecal microbiota transplantation (FMT) in animals; however, the usage of FMT in humans needs further clarification and review. We explored PubMed, Popline, and Cochrane Library to identify relevant papers. Eight articles were then finalized after screening and applying eligibility criteria. These articles explored the role of the therapeutic efficacy of FMT in insulin resistance and hyperglycemia. The studies showed that the FMT had a positive impact on managing hyperglycemia and insulin resistance, which is evident in the decline of blood glucose and HBA1c levels and the rise of insulin and C-peptides. In addition, FMT also helped to control other risk factors such as hyperlipidemia and blood pressure; however, the impact on weight loss is not convincing. FMT also influenced the levels of some microbiota, which could be involved in controlling hyperglycemia and insulin resistance. Due to limited control trials and study periods and the small sample size of diabetic patients, more research is needed to explore the impact of FMT in controlling type 2 diabetes mellitus.}, }
@article {pmid39482760, year = {2024}, author = {Nie, D and Wang, D and Wang, Z and Fang, Q and Wang, H and Xie, W and Li, C and Zhang, Y}, title = {The gut microbiome in patients with Cushing's disease affects depression- and anxiety-like behavior in mice.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {225}, pmid = {39482760}, issn = {2049-2618}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Pituitary ACTH Hypersecretion/microbiology/psychology/physiopathology ; *Depression/microbiology ; *Anxiety/microbiology ; Humans ; *Disease Models, Animal ; Male ; Behavior, Animal ; Feces/microbiology ; Female ; Corticosterone/blood ; Bacteria/classification/isolation &amp; purification ; Adult ; Middle Aged ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Depression and anxiety significantly impact the quality of life in individuals with Cushing's disease (CD), which originates from pituitary neuroendocrine tumors (PitNETs), yet our understanding of the underlying mechanisms is limited. There is substantial evidence linking gut microbes to depression, anxiety, and endocrinology.<br><br>RESULTS: The gut bacterial phenotype of patients with Cushing's disease was significantly different from that of the control group, and when the mice were treated with fecal bacteria from these patients, both anxiety- and depression-like behavior were significantly increased. However, this effect can be alleviated by supplementing with 2-(14, 15-epoxyeicosatrienoyl) glycerol (2-14,15-EG) which was found at reduced levels in the peripheral blood of mice treated with coprofecal bacteria from Cushing's disease. In this process, the effects of hormone levels and immune factors were not significant. In addition, in an animal model, corticosterone has been observed to affect behavioral changes in mice through gut microbiota composition, clarifying the cause-and-effect relationship between hormones, microbiota, and behavior. Finally, there was no significant difference in gut microbiome composition and its effects on mouse behavior in patients with Cushing's disease with different levels of depression and anxiety.<br><br>CONCLUSIONS: In summary, this research enhances our current understanding of how gut microbes in patients with Cushing's disease contribute to depression and anxiety, offering novel insights for clinical treatment approaches. Video Abstract.}, }
@article {pmid39488230, year = {2024}, author = {Rubak, T and Baunwall, SMD and Gregersen, M and Paaske, SE and Asferg, M and Barat, I and Secher-Johnsen, J and Riis, MG and Rosenbæk, JB and Hansen, TK and Ørum, M and Steves, CJ and Veilbæk, H and Hvas, CL and Damsgaard, EMS}, title = {Early geriatric assessment and management in older patients with Clostridioides difficile infection in Denmark (CLODIfrail): a randomised trial.}, journal = {The lancet. Healthy longevity}, volume = {5}, number = {12}, pages = {100648}, doi = {10.1016/j.lanhl.2024.100648}, pmid = {39488230}, issn = {2666-7568}, mesh = {Humans ; Aged ; Male ; Female ; Denmark/epidemiology ; *Clostridium Infections/mortality/therapy/drug therapy ; *Geriatric Assessment ; Aged, 80 and over ; Clostridioides difficile ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {BACKGROUND: Clostridioides difficile infection causes diarrhoea and colitis. Older patients with C difficile infection are often frail and have comorbidities, leading to high mortality rates. The frailty burden in older people might restrict access to treatments, such as C difficile infection-specific antibiotics and faecal microbiota transplantation. We aimed to investigate the clinical effects of early comprehensive geriatric assessment (CGA) and frailty evaluation, including home visits and assessment for faecal microbiota transplantation, in older patients with C difficile infection.<br><br>METHODS: In this randomised, quality improvement trial with a pragmatic design, patients from the Central Denmark Region aged 70&#xa0;years or older with a positive PCR test for C&#xa0;difficile toxin were randomly assigned (1:1) to CGA or standard care, both with equal access to faecal microbiota transplantation. Patients and investigators were unmasked to treatment. The primary outcome was 90-day mortality, and was compared in the study groups according to the intention-to-treat principle. The study is registered with ClinicalTrials.gov, NCT05447533.<br><br>FINDINGS: Between Sept 1, 2022, and May 3, 2023, we randomly assigned 217&#xa0;patients to CGA (n=109) or standard care (n=108). The median patient age was 78&#xa0;years (IQR 74-84). 116 (53%) of 217&#xa0;patients were female and 101 (47%) were male. 16 (15%; 95% CI 9-23) of 109&#xa0;patients in the CGA group and 22 (20%; 14-29) of 108&#xa0;patients in the standard-care group died within 90&#xa0;days (odds ratio 0&#xb7;66, 95% CI 0&#xb7;32-1&#xb7;38. No serious adverse events or deaths related to patient assessment or faecal microbiota transplantation were recorded in either group. Deaths directly attributable to C&#xa0;difficile infection were lower in the CGA group (seven [44%] of 16&#xa0;deaths vs 18 [82%] of 22&#xa0;deaths in the standard-care group; p=0&#xb7;020).<br><br>INTERPRETATION: Older patients who received CGA had a 90-day mortality rate similar to that of patients who received standard care, but with fewer deaths directly attributable to C&#xa0;difficile infection.<br><br>FUNDING: Innovation Fund Denmark, Novo Nordisk Foundation, and Helsefonden.}, }
@article {pmid39486524, year = {2024}, author = {Kapoor, B and Biswas, P and Gulati, M and Rani, P and Gupta, R}, title = {Gut microbiome and Alzheimer's disease: What we know and what remains to be explored.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102570}, doi = {10.1016/j.arr.2024.102570}, pmid = {39486524}, issn = {1872-9649}, mesh = {Animals ; Humans ; *Alzheimer Disease/metabolism/microbiology/physiopathology ; Brain/metabolism/physiopathology ; *Brain-Gut Axis/physiology ; *Dysbiosis/microbiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; }, abstract = {With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of gut microbiota in the pathogenesis of Alzheimer disease. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts influence not only various gut disorder but also central nervous system disorders such as AD. On the basis of accumulated evidences of past few years now it is quite clear that the gut microbiota can control the functions of the central nervous system (CNS) through the gut-brain axis, which provides a new prospective into the interactions between the gut and brain. The main focus of this review is on the molecular mechanism of the crosstalk between the gut microbiota and the brain through the gut-brain axis, and on the onset and development of neurological disorders triggered by the dysbiosis of gut microbiota. Due to microbiota dysbiosis the permeability of the gut and blood brain barrier is increased which may mediate or affect AD. Along with this, bacterial population of the gut microbiota can secrete amyloid proteins and lipopolysaccharides in a large quantity which may create a disturbance in the signaling pathways and the formation of proinflammatory cytokines associated with the pathogenesis of AD. These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis, including the use of probiotics, prebiotics, metabolites, diets and fecal microbiota transplantation. The main purpose of this review includes the summarization and discussion on the recent finding that may explain the role of the gut microbiota in the development of AD. Understanding of these fundamental mechanisms may provide a new insight into the novel therapeutic strategies for AD.}, }
@article {pmid39486483, year = {2025}, author = {Lu, H and Xie, L and Guo, L and Gu, X and Zhu, R and Yang, Y and Tang, F and Li, M and Liu, C and Wang, D and Li, M and Tian, Y and Cai, S}, title = {EGCG protects intestines of mice and pelvic cancer patients against radiation injury via the gut microbiota/D-tagatose/AMPK axis.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {202}, number = {}, pages = {110608}, doi = {10.1016/j.radonc.2024.110608}, pmid = {39486483}, issn = {1879-0887}, mesh = {Animals ; *Catechin/analogs &amp; derivatives/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Mice ; Humans ; *Radiation Injuries/prevention &amp; control ; *Pelvic Neoplasms/radiotherapy ; Female ; Intestines/radiation effects/drug effects/microbiology ; Radiation-Protective Agents/pharmacology/therapeutic use ; Male ; Mice, Inbred C57BL ; AMP-Activated Protein Kinases/metabolism ; }, abstract = {BACKGROUND AND PURPOSE: Radiation-induced intestinal injury (RIII) compromises the clinical utility of pelvic radiotherapy (RT). We aimed to explore the protective effect and underlying mechanism of (-)-epigallocatechin-3-gallate (EGCG) on RIII.<br><br>MATERIALS AND METHODS: We evaluated the protective effect of EGCG on intestine in RIII mouse model and pelvic cancer patients, while explored the underlying mechanism through (1) 16S rRNA sequencing, (2) metabolomic profiles, (3) fresh sterile fecal filtrate (SFF) transplantation, and (4) transcriptome sequencing.<br><br>RESULTS: EGCG efficiently prevented RIII in mouse, as reflected by improved survival, alleviated intestinal structure damage, promoted intestinal regeneration, and ameliorated gut microbiota dysbiosis. Prophylactic EGCG intervention reduced the severity of RIII in patients receiving pelvic RT. Mechanistically, the protective effect of EGCG could be transferred to other mice by SFF transplantation. EGCG enriched gut microbiota-derived metabolite D-tagatose, and oral administration of D-tagatose reproduced the radio-protective effect of EGCG via activating AMPK.<br><br>CONCLUSION: Oral EGCG may be a promising strategy for preventing RIII clinically, and warrant further investigation in prospective randomized phase III trials.}, }
@article {pmid39486191, year = {2024}, author = {Singh, R and Panganiban, K and Au, E and Ravikumar, R and Pereira, S and Prevot, TD and Mueller, DJ and Remington, G and Agarwal, SM and Verdu, EF and Bercik, P and De Palma, G and Hahn, MK}, title = {Human-fecal microbiota transplantation in relation to gut microbiome signatures in animal models for schizophrenia: A scoping review.}, journal = {Asian journal of psychiatry}, volume = {102}, number = {}, pages = {104285}, doi = {10.1016/j.ajp.2024.104285}, pmid = {39486191}, issn = {1876-2026}, mesh = {*Fecal Microbiota Transplantation ; Animals ; *Schizophrenia/therapy/metabolism ; *Gastrointestinal Microbiome/physiology ; *Disease Models, Animal ; Humans ; Mice ; }, abstract = {More recently, attention has turned to the putative role of gut microbiome (GMB) in pathogenesis, symptomatology, treatment response and/or resistance in schizophrenia (SCZ). It is foreseeable that fecal microbiota transplantation (FMT) from SCZ patients (SCZ-FMT) to germ-free mice could represent a suitable experimental framework for a better understanding of the relationship between GMB and SCZ. Thus, we set out to identify literature (i) characterizing the GMB in animal models of SCZ, and (ii) employing SCZ-FMT into rodents to model SCZ in relation to behavioral and molecular phenotypes. Five studies examining animal models of SCZ suggest distinct GMB composition compared to respective control groups, which was correlated with SCZ-like behavioral phenotypes. Four additional studies investigated SCZ-FMT into rodents in relation to behavioral phenotypes, including spontaneous hyperlocomotion, social deficits, exaggerated startle response, and cognitive impairments, resembling those observed in SCZ patients. Mice receiving SCZ-FMT showed altered neurochemical and metabolic pathways in the brain. Animal models of SCZ have shown altered GMB composition, whereas reported behavioral and neurochemical alterations following FMT from patients into rodents suggest early face and construct validity for SCZ-FMT animal models. However, the predictive validity of these models remains to be validated.}, }
@article {pmid39485288, year = {2024}, author = {Minaya, DM and Kim, JS and Kirkland, R and Allen, J and Cullinan, S and Maclang, N and de Lartigue, G and de La Serre, C}, title = {Transfer of microbiota from lean donors in combination with prebiotics prevents excessive weight gain and improves gut-brain vagal signaling in obese rats.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2421581}, pmid = {39485288}, issn = {1949-0984}, mesh = {Animals ; *Obesity/microbiology/metabolism ; Male ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Prebiotics/administration &amp; dosage ; *Brain-Gut Axis/physiology ; *Diet, High-Fat/adverse effects ; *Vagus Nerve ; *Weight Gain/drug effects ; Dysbiosis/microbiology ; Rats, Sprague-Dawley ; Bacteria/classification/isolation &amp; purification/genetics/metabolism ; Fecal Microbiota Transplantation ; Brain/metabolism ; Signal Transduction ; }, abstract = {Gastrointestinal (GI) microbiota plays an active role in regulating the host's immune system and metabolism, as well as certain pathophysiological processes. Diet is the main factor modulating GI microbiota composition and studies have shown that high fat (HF) diets induce detrimental changes (dysbiosis) in the GI bacterial makeup. HF diet induced dysbiosis has been associated with structural and functional changes in gut-brain vagally mediated signaling system, associated with overeating and obesity. Although HF-driven changes in microbiota composition are sufficient to alter vagal signaling, it is unknown if improving microbiota composition after diet-induced obesity has been established can ameliorate gut-brain signaling and metabolic outcomes. In this study, we evaluated the effect of lean gut microbiota transfer in obese, vagally compromised, rats on gut-brain communication, food intake, and body weight. Male rats were maintained on regular chow or 45% HF diet for nine weeks followed by three weeks of microbiota depletion using antibiotics. The animals were then divided into four groups (n = 10 each): LF - control fed regular chow, LF-LF - chow fed animals that received microbiota from chow fed donors, HF-LF - HF fed animals that received microbiota from chow fed donors, and HF-HF - HF fed animals that received microbiota from HF fed donors. HF-LF animals received inulin as a prebiotic to aid the establishment of the lean microbiome. We found that transferring a LF microbiota to HF fed animals (HF-LF) reduced caloric intake during the light phase when compared with HF-HF rats and prevented additional excessive weight gain. HF-LF animals displayed an increase in postprandial activation of both primary sensory neurons innervating the GI tract and brainstem secondary neurons. We concluded from these data that improving microbiota composition in obese rats is sufficient to ameliorate gut-brain communication and restore normal feeding patterns which was associated with a reduction in weight gain.}, }
@article {pmid39484785, year = {2025}, author = {Li, Y and Song, X and Dai, L and Wang, Y and Luo, Q and Lei, L and Pu, Y}, title = {Mechanism of action of exercise regulating intestinal microflora to improve spontaneous hypertension in rats.}, journal = {Biomolecules &amp; biomedicine}, volume = {25}, number = {3}, pages = {648-662}, pmid = {39484785}, issn = {2831-090X}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Hypertension/microbiology/therapy/physiopathology ; *Physical Conditioning, Animal ; Rats, Inbred SHR ; Rats ; Male ; Blood Pressure ; Ileum/pathology/microbiology ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Hypertension is a prevalent cardiovascular disease. Exercise is widely recognized as an effective treatment for hypertension, and it may also influence the composition of the intestinal microflora. However, it remains unclear whether exercise can specifically regulate the intestinal microflora in the context of hypertension treatment. In this study, tail blood pressure in spontaneously hypertensive rats (SHR) was measured using a blood pressure meter after exercise intervention and fecal bacteria transplantation following exercise. Blood lipid levels were assessed using an automatic biochemical analyzer, and 16S rRNA sequencing was employed to analyze the intestinal microflora. Histological examinations of ileal tissue were conducted using HE and Masson staining. Intestinal permeability, inflammatory status, and sympathetic activity were evaluated by measuring the levels of diamine oxidase, D-lactic acid, C-reactive protein, interleukin-6, tumor necrosis factor-α, lipopolysaccharide, norepinephrine, angiotensin II, cyclic adenosine monophosphate, and cyclic guanosine monophosphate. Exercise was found to reduce blood pressure and blood lipid levels in SHR. It also improved the composition of the intestinal microflora, as evidenced by a reduced Firmicutes/Bacteroidetes ratio, an increase in bacteria that produce acetic and butyric acid, and higher Chao 1 and Shannon diversity indices. Furthermore, exercise reduced the thickness of the fibrotic and muscular layers in the ileum, increased the goblet cell/villus ratio and villus length, and decreased intestinal permeability, inflammatory markers, and sympathetic nerve activity. The intestinal microbial flora regulated by exercise demonstrated similar effects on hypertension. In conclusion, exercise appears to regulate the intestinal microflora, and this exercise-induced change in flora may contribute to improvements in hypertension in rats.}, }
@article {pmid39482823, year = {2025}, author = {Zhang, T and Li, X and Li, J and Sun, F and Duan, L}, title = {Gut microbiome-targeted therapies as adjuvant treatments in inflammatory bowel diseases: a systematic review and network meta-analysis.}, journal = {Journal of gastroenterology and hepatology}, volume = {40}, number = {1}, pages = {78-88}, doi = {10.1111/jgh.16795}, pmid = {39482823}, issn = {1440-1746}, support = {2021YFA1301300//National Key Research and Development Program of China/ ; 82170557//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use/administration &amp; dosage ; *Fecal Microbiota Transplantation/methods ; *Prebiotics/administration &amp; dosage ; Synbiotics/administration &amp; dosage ; Treatment Outcome ; *Colitis, Ulcerative/therapy/microbiology ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Crohn Disease/therapy/microbiology ; Randomized Controlled Trials as Topic ; Combined Modality Therapy ; Remission Induction ; }, abstract = {BACKGROUND AND AIM: Gut microbiome-targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta-analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD).<br><br>METHODS: We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values.<br><br>RESULTS: Thirty-eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo-oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD.<br><br>CONCLUSIONS: FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary.}, }
@article {pmid39481287, year = {2024}, author = {Gautam, R and Maan, P and Patel, AK and Vasudevan, S and Arora, T}, title = {Unveiling the complex interplay between gut microbiota and polycystic ovary syndrome: A narrative review.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {12}, pages = {199-208}, doi = {10.1016/j.clnu.2024.10.028}, pmid = {39481287}, issn = {1532-1983}, mesh = {*Polycystic Ovary Syndrome/microbiology/therapy/physiopathology ; Humans ; *Gastrointestinal Microbiome/physiology ; Female ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; Diet/methods ; Brain-Gut Axis/physiology ; Fecal Microbiota Transplantation ; Fatty Acids, Volatile/metabolism ; }, abstract = {BACKGROUND &amp; AIM: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects women throughout their reproductive age and characterised via polycystic ovaries, hyperandrogenism, and irregular menstruation. There is rising evidence that the pathophysiology of PCOS is significantly affected via the gut microbiota and its metabolic products.<br><br>METHODS: This narrative review synthesizes current literature exploring the relationship between gut microbiota and PCOS. A comprehensive search of electronic databases was conducted to identify relevant studies. Further this review also analysed therapeutic options of probiotics, prebiotics, Fecal Microbiota Transplant (FMT), high fiber and poly phenol rich diet and novel therapeutic agents in treatment of PCOS.<br><br>RESULTS: Emerging evidence suggests alterations in the composition and diversity of gut microbiota in women with PCOS. The current literature showed a complex relationship of gut microbiota, short chain fatty acids (SCFAs) metabolism, intestinal permeability and LPS (Lipid Polysaccharide) metabolism, gut-brain axis and bile acid (BA) pathway within etiology and pathophysiology of PCOS. Additionally, the factors such as diet, lifestyle, genetics, and environmental influences may all contribute to alterations in gut microbiota that could potentially exacerbate or mitigate PCOS symptoms.<br><br>CONCLUSION: The review provides valuable insights into the intricate interplay between the gut and female reproductive health. The present evidence suggested that alterations in diversity and function of the gut microbiota may lead to specific pathogenic changes that lead to development of PCOS. A comprehensive understanding of these microbial dynamics may lead to new therapeutic approaches that target the gut micro biome.}, }
@article {pmid39480487, year = {2024}, author = {Deda, O and Armitage, EG and Mouskeftara, T and Kachrimanidou, M and Zervos, I and Malousi, A and Loftus, NJ and Taitzoglou, I and Gika, H}, title = {Unraveling Cecal Alterations in Clostridioides difficile Colonized Mice through Comprehensive Metabolic Profiling.}, journal = {Journal of proteome research}, volume = {23}, number = {12}, pages = {5462-5475}, pmid = {39480487}, issn = {1535-3907}, mesh = {Animals ; *Cecum/microbiology/metabolism ; *Clostridioides difficile/metabolism ; Mice ; *Metabolome/drug effects ; *Metabolomics/methods ; Clostridium Infections/metabolism/microbiology ; Tandem Mass Spectrometry ; Gastrointestinal Microbiome/physiology ; Gas Chromatography-Mass Spectrometry/methods ; Metronidazole/pharmacology ; Anti-Bacterial Agents/pharmacology ; Fecal Microbiota Transplantation ; Disease Models, Animal ; }, abstract = {The disruption of gut microbiota caused by antibiotics favors the intestinal colonization of Clostridioides difficile - a Gram-positive, spore-forming anaerobic bacterium that causes potentially fatal gastrointestinal infections. In an endeavor to elucidate the complexities of the gut-brain axis in the context of Clostridium difficile infection (CDI), a murine model has been used to investigate the potential effects of antibiotic administration and subsequent colonization by C. difficile, as well as the impact of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the cecal metabolome for the first time. This follows our previous research which highlighted the metabolic effect of CDI and these treatments in the brain and employs the same four different metabolomics-based methods (targeted GC-MS/MS, targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS and untargeted GC-MS). A total of 286 unique metabolites have been identified in the mouse cecal profiles and statistical analysis revealed that CDI, as well as the subsequent treatments, significantly alters cecal metabolites and lipids implicated in various biochemical pathways centered around amino acid metabolism, glycerophospholipid metabolism, and central carbon metabolism. To our knowledge, this study represents the first exploration of the effects of C. difficile-induced colitis and potential treatments on the cecal tissue metabolome.}, }
@article {pmid39479215, year = {2024}, author = {Huang, J and Xu, T and Quan, G and Li, Y and Yang, X and Xie, W}, title = {Current progress on the microbial therapies for acute liver failure.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1452663}, pmid = {39479215}, issn = {1664-302X}, abstract = {Acute liver failure (ALF), associated with a clinical fatality rate exceeding 80%, is characterized by severe liver damage resulting from various factors in the absence of pre-existing liver disease. The role of microbiota in the progression of diverse liver diseases, including ALF, has been increasingly recognized, with the interactions between the microbiota and the host significantly influencing both disease onset and progression. Despite growing interest in the microbiological aspects of ALF, comprehensive reviews remain limited. This review critically examines the mechanisms and efficacy of microbiota-based treatments for ALF, focusing on their role in prevention, treatment, and prognosis over the past decade.}, }
@article {pmid39473963, year = {2024}, author = {Wang, YN and Zhai, XY and Wang, Z and Gao, CL and Mi, SC and Tang, WL and Fu, XM and Li, HB and Yue, LF and Li, PF and Xi, SY}, title = {Jianpi-Huatan-Huoxue-Anshen formula ameliorates gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with H22 hepatocellular carcinoma.}, journal = {World journal of gastrointestinal oncology}, volume = {16}, number = {10}, pages = {4209-4231}, pmid = {39473963}, issn = {1948-5204}, abstract = {BACKGROUND: Jianpi-Huatan-Huoxue-Anshen formula [Tzu-Chi cancer-antagonizing &amp; life-protecting II decoction (TCCL)] is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life. However, its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear.<br><br>AIM: To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC).<br><br>METHODS: Ninety-six mice were inoculated subcutaneously with HCC cells. One week later, the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model. Thirty-six mice were randomly selected before administration, and feces, ileal tissue, and ileal contents were collected from each mouse. The remaining mice were randomized into normal saline, continuous chemotherapy, Yangzheng Xiaoji capsules-treated, and three TCCL-treated groups. After treatment, feces, tumors, liver, spleen, thymus, stomach, jejunum, ileum, and colon tissues, and ileal contents were collected. Morphological changes, serum levels of IL-1&#x3b2;, IL-6, IL-8, IL-10, IL-22, TNF-&#x3b1;, and TGF-&#x3b2;, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-&#x3ba;B, Occludin, MUC-2, Claudin-1, and I&#x3ba;B-&#x3b1; in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing.<br><br>RESULTS: TCCL treatment improved thymus and spleen weight, thymus and spleen indexes, and body weight, decreased tumor volumes and tumor tissue cell density, and alleviated injury to gastric, ileal, and colonic mucosal tissues. Among proteins and genes associated with inflammation, IL-10, TGF-&#x3b2;, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-&#x3ba;B, IL-1&#x3b2;, IL-6, TNF-&#x3b1;, IL-22, IL-8, and I&#x3ba;B-&#x3b1; were downregulated. Additionally, TCCL increased the proportions of fecal Actinobacteria, AF12, Adlercreutzia, Clostridium, Coriobacteriaceae, and Paraprevotella in the intermediate stage of treatment, decreased the proportions of Mucipirillum, Odoribacter, RF32, YS2, and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment. Studies on ileal mucosal microbiota showed similar findings. Moreover, TCCL improved community richness, evenness, and the diversity of fecal and ileal mucosal flora.<br><br>CONCLUSION: TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy.}, }
@article {pmid39471905, year = {2025}, author = {Salia, S and Burke, FF and Hinks, ME and Randell, AM and Matheson, MA and Walling, SG and Swift-Gallant, A}, title = {Gut microbiota transfer from the preclinical maternal immune activation model of autism is sufficient to induce sex-specific alterations in immune response and behavioural outcomes.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {813-823}, doi = {10.1016/j.bbi.2024.10.030}, pmid = {39471905}, issn = {1090-2139}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; Female ; Male ; Mice ; *Disease Models, Animal ; *Mice, Inbred C57BL ; *Autism Spectrum Disorder/immunology/microbiology ; *Behavior, Animal/physiology ; Pregnancy ; Fecal Microbiota Transplantation ; Autistic Disorder/immunology/microbiology ; Sex Characteristics ; Social Behavior ; Sex Factors ; Anxiety/immunology/microbiology ; Cytokines/metabolism ; }, abstract = {The gut microbiome plays a vital role in health and disease, including neurodevelopmental disorders like autism spectrum disorder (ASD). ASD affects 4:1 males-to-females, and sex differences are apparent in gut microbiota composition among ASD individuals and in animal models of this condition, such as the maternal immune activation (MIA) mouse model. However, few studies have included sex as a biological variable when assessing the role of gut microbiota in mediating ASD symptoms. Using the MIA model of ASD, we assessed whether gut microbiota contributes to the sex differences in the presentation of ASD-like behaviors. Gut microbiota transplantation from MIA or vehicle/control male and female mice into healthy, otherwise unmanipulated, 4-week-old C57Bl/6 mice was performed for 6 treatments over 12 days. Colonization with male, but not female, MIA microbiota was sufficient to reduce sociability, decrease microbiota diversity and increase neuroinflammation with more pronounced deficits in male recipients. Colonization with both male and female donor microbiota altered juvenile ultrasonic vocalizations and anxiety-like behavior in recipients of both sexes, and there was an accompanied change in the gut microbiota and serum cytokine IL-4 and IL-7 levels of all recipients of MIA gut microbiota. In addition to the increases in gut microbes associated with pathological states, the female donor microbiota profile also had increases in gut microbes with known neural protective effects (e.g., Lactobacillus and Rikenella). These results suggest that gut reactivity to environmental insults, such as in the MIA model, may play a role in shaping the sex disparity in ASD development.}, }
@article {pmid39471749, year = {2024}, author = {Liu, X and Lu, B and Tang, H and Jia, X and Zhou, Q and Zeng, Y and Gao, X and Chen, M and Xu, Y and Wang, M and Tan, B and Li, J}, title = {Gut microbiome metabolites, molecular mimicry, and species-level variation drive long-term efficacy and adverse event outcomes in lung cancer survivors.}, journal = {EBioMedicine}, volume = {109}, number = {}, pages = {105427}, pmid = {39471749}, issn = {2352-3964}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Lung Neoplasms/drug therapy/immunology/pathology ; Male ; Female ; Middle Aged ; Aged ; Cancer Survivors ; Metabolome ; Metagenome ; Metagenomics/methods ; Immune Checkpoint Inhibitors/therapeutic use/adverse effects ; Treatment Outcome ; }, abstract = {BACKGROUND: The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms.<br><br>METHODS: We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts).<br><br>FINDINGS: The ICI benefit group was enriched for propionate (P&#xa0;=&#xa0;0.01) and butyrate/isobutyrate (P&#xa0;=&#xa0;0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P&#xa0;<&#xa0;0.001, butyrate/isobutyrate P&#xa0;=&#xa0;0.002). The acetyl-CoA pathway (P&#xa0;=&#xa0;0.02) in beneficial species mainly mediated butyrate production. Microbiota sequences from irAE patients aligned with antigenic epitopes found in autoimmune diseases. Microbiotas of responsive patients contained more lung cancer-related antigens (P&#xa0;=&#xa0;0.07), which was validated in the Routy cohort (P&#xa0;=&#xa0;0.02). Escherichia coli and SGB15342 of Faecalibacterium prausnitzii showed strain-level variations corresponding to clinical phenotypes. Metabolome validation reviewed more abundant acetic acid (P&#xa0;=&#xa0;0.03), propionic acid (P&#xa0;=&#xa0;0.09), and butyric acid (P&#xa0;=&#xa0;0.02) in the benefit group than the resistance group, and patients with higher acetic, propionic, and butyric acid levels had a longer progression-free survival and lower risk of tumor progression after adjusting for histopathological subtype and stage (P&#xa0;<&#xa0;0.05).<br><br>INTERPRETATION: Long-term ICI survivors have coevolved a compact microbial community with high butyrate production, and molecular mimicry of autoimmune and tumor antigens by microbiota contribute to outcomes. These results not only characterize the gut microbiotas of patients who benefit long term from ICIs but pave the way for "smart" fecal microbiota transplantation. Registered in the Chinese Clinical Trial Registry (ChiCTR2000032088).<br><br>FUNDING: This work was supported by Beijing Natural Science Foundation (7232110), National High Level Hospital Clinical Research Funding (2022-PUMCH-A-072, 2023-PUMCH-C-054), CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&amp;T-B-010).}, }
@article {pmid39471538, year = {2024}, author = {Levitte, S and Nilkant, R and Jensen, AR and Zhang, KY}, title = {Unlocking the promise of mesenchymal stem cells and extracorporeal photopheresis to address rejection and graft failure in intestinal transplant recipients.}, journal = {Human immunology}, volume = {85}, number = {6}, pages = {111160}, doi = {10.1016/j.humimm.2024.111160}, pmid = {39471538}, issn = {1879-1166}, mesh = {Humans ; *Photopheresis/methods ; *Graft Rejection/immunology ; Male ; Female ; Retrospective Studies ; *Intestines/pathology/immunology ; Adult ; *Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/immunology ; Child ; Middle Aged ; Treatment Outcome ; Extracellular Vesicles ; Immunosuppressive Agents/therapeutic use ; Transplant Recipients ; Adolescent ; }, abstract = {INTRODUCTION: In patients with irreversible intestinal failure, intestinal transplant has become a standard treatment option. Graft failure secondary to acute or chronic cellular rejection continues to be a significant challenge following transplant. Even with optimal immune suppression, some patients continue to struggle with refractory rejection. Both extracorporeal photopheresis (ECP) and extracellular vesicles derived from mesenchymal stem cells (EVs) have been used to treat refractory rejection following intestinal transplantation, although their use remains limited and consistent treatment protocols are lacking.<br><br>METHODS: Intestinal transplant recipients who received ECP only or ECP and EVs as rescue therapy for acute cellular rejection or chronic inflammation between 2016 and 2022 were included in this single-center retrospective analysis. Baseline demographics, pre- and post-treatment histopathology, endoscopic and biochemical findings, and long-term transplant outcomes were analyzed.<br><br>RESULTS: Three patients (two pediatric and one adult) with acute steroid- and biologic-refractory rejection were treated with ECP and/or EVs, as was one patient (pediatric) with chronic graft rejection and inflammation. Patients received twice weekly ECP for 4&#xa0;weeks and once weekly thereafter. EVs were administered in three doses each separated by 72&#xa0;h. Immunosuppression at the time of treatment initiation included high-dose tacrolimus and sirolimus. Histologic resolution of rejection was achieved in all patients over 12-16&#xa0;weeks. Steroids were weaned to low-dose or withdrawn in every patient within 4&#xa0;weeks of ECP/EV treatment. C-reactive protein decreased from an average of 14.75 to 1.6&#xa0;mg/dL post-treatment and fecal calprotectin decreased from average 800&#xa0;mg/g to 31&#xa0;mg/g. Donor-induced cytotoxic T cell populations were quantified for two of the patients with acute rejection, and in both cases decreased dramatically following treatment. There were no complications associated with either treatment.<br><br>CONCLUSION: Both ECP and EVs present novel opportunities to address graft rejection and inflammation in bowel transplant recipients. More work will be needed to define the optimal therapeutic parameters for each treatment modality.}, }
@article {pmid39470619, year = {2024}, author = {Liu, X and Luo, Y and Chen, X and Wu, M and Xu, X and Tian, J and Gao, Y and Zhu, J and Wang, Z and Zhou, Y and Zhang, Y and Wang, X and Li, W and Lu, Q and Yao, X}, title = {Fecal microbiota transplantation against moderate-to-severe atopic dermatitis: A randomized, double-blind controlled explorer trial.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.16372}, pmid = {39470619}, issn = {1398-9995}, support = {//Nanjing Incubation Program for National Clinical Research Center/ ; //National Key Research and Development Program of China/ ; //CAMS Innovation Fund for Medical Sciences/ ; //Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; //National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate-to-severe atopic dermatitis (AD).<br><br>METHODS: In this randomized, double-blind, placebo-controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate-to-severe adult patients with AD. All patients received FMT or placebo once a week for 3&#x2009;weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial.<br><br>RESULTS: Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo-treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF-&#x3b1;, and total IgE in serum. By contrast, the expression levels of IL-12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4-dihydroxy-6-naphthoate biosynthesis II.<br><br>CONCLUSION: FMT was a safe and effective therapy in moderate-to-severe adult patients with AD; the treatment changed the gut microbiota compositions and functions.}, }
@article {pmid39470206, year = {2024}, author = {Todd, CL and Johnson, EE and Stewart, F and Wallace, SA and Bryant, A and Woodward, S and Norton, C}, title = {Conservative, physical and surgical interventions for managing faecal incontinence and constipation in adults with central neurological diseases.}, journal = {The Cochrane database of systematic reviews}, volume = {10}, number = {10}, pages = {CD002115}, pmid = {39470206}, issn = {1469-493X}, mesh = {Adult ; Humans ; Bias ; *Central Nervous System Diseases/complications ; Conservative Treatment/methods ; *Constipation/therapy/etiology ; *Fecal Incontinence/therapy/etiology ; Quality of Life ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: People with central neurological disease or injury have a much higher risk of both faecal incontinence (FI) and constipation than the general population. There is often a fine line between the two symptoms, with management intended to ameliorate one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical, with a limited research base. The review is relevant to individuals with any disease directly and chronically affecting the central nervous system (post-traumatic, degenerative, ischaemic or neoplastic), such as multiple sclerosis, spinal cord injury, cerebrovascular disease, Parkinson's disease and Alzheimer's disease. This is an update of a Cochrane Review first published in 2001 and subsequently updated in 2003, 2006 and 2014.<br><br>OBJECTIVES: To assess the effects of conservative, physical and surgical interventions for managing FI and constipation in people with a neurological disease or injury affecting the central nervous system.<br><br>SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register (searched 27 March 2023), which includes searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP as well as handsearching of journals and conference proceedings; and all reference lists of relevant articles.<br><br>SELECTION CRITERIA: We included randomised, quasi-randomised (where allocation is not strictly random), cross-over and cluster-randomised trials evaluating any type of conservative, physical or surgical intervention against placebo, usual care or no intervention for the management of FI and constipation in people with central neurological disease or injury.<br><br>DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the risk of bias in eligible trials using Cochrane's 'Risk of bias' tool and independently extracted data from the included trials using a range of prespecified outcome measures. We produced summary of findings tables for our main outcome measures and assessed the certainty of the evidence using GRADE.<br><br>MAIN RESULTS: We included 25 studies with 1598 participants. The studies were generally at high risk of bias due to lack of blinding of participants and personnel to the intervention. Half of the included studies were also at high risk of bias in terms of selective reporting. Outcomes were often reported heterogeneously across studies, making it difficult to pool data. We did not find enough evidence to be able to analyse the effects of interventions on individual central neurological diseases. Additionally, very few studies reported on the primary outcomes of self-reported improvement in FI or constipation, or Neurogenic Bowel Dysfunction Score. Conservative interventions compared with usual care, no active treatment or placebo Thirteen studies assessed this comparison. The interventions included assessment-based nursing, holistic nursing, probiotics, psyllium, faecal microbiota transplantation, and a stepwise protocol of increasingly invasive evacuation methods. Conservative interventions may result in a large improvement in faecal incontinence (standardised mean difference (SMD) -1.85, 95% confidence interval (CI) -3.47 to -0.23; 3 studies; n = 410; low-certainty evidence). We interpreted SMD &#x2265; 0.80 as a large effect. It was not possible to pool all data from studies that assessed improvement in constipation, but the evidence suggested that conservative interventions may improve constipation symptoms (data not pooled; 8 studies; n = 612; low-certainty evidence). Conservative interventions may lead to a reduction in mean time taken on bowel care (data not pooled; 5 studies; n = 526; low-certainty evidence). The evidence is uncertain about the effects of conservative interventions on condition-specific quality of life and adverse events. Neurogenic Bowel Dysfunction Score was not reported. Physical therapy compared with usual care, no active treatment or placebo Twelve studies assessed this comparison. The interventions included massage therapy, standing, osteopathic manipulative treatment, electrical stimulation, transanal irrigation, and conventional physical therapy with visceral mobilisation. Physical therapies may make little to no difference to self-reported faecal continence assessed using the St Mark's Faecal Incontinence Score, where the minimally important difference is five, or the Cleveland Constipation Score (MD -2.60, 95% CI -4.91 to -0.29; 3 studies; n = 155; low-certainty evidence). Physical therapies may result in a moderate improvement in constipation symptoms (SMD -0.62, 95% CI -1.10 to -0.14; 9 studies; n = 431; low-certainty evidence). We interpreted SMD &#x2265; 0.5 as a moderate effect. However, physical therapies may make little to no difference in Neurogenic Bowel Dysfunction Score as the minimally important difference for this tool is 3 (MD -1.94, 95% CI -3.36 to -0.51; 7 studies; n = 358; low-certainty evidence). We are very uncertain about the effects of physical therapies on the time spent on bowel care, condition-specific quality of life and adverse effects (all very low-certainty evidence). Surgical interventions compared with usual care, no active treatment or placebo No studies were found for surgical interventions that met the inclusion criteria for this review.<br><br>AUTHORS' CONCLUSIONS: There remains little research on this common and, for patients, very significant issue of bowel management. The available evidence is almost uniformly of low methodological quality. The clinical significance of some of the research findings presented here is difficult to interpret, not least because each intervention has only been addressed in individual trials, against control rather than compared against each other, and the interventions are very different from each other. Understanding whether there is a clinically-meaningful difference from the results of available trials is largely hampered by the lack of uniform outcome measures. This is due to an absence of core outcome sets, and development of these needs to be a research priority to allow studies to be compared directly. Some studies used validated constipation, incontinence or condition-specific measures; however, others used unvalidated analogue scales to report effectiveness. Some studies did not use any patient-reported outcomes and focused on physiological outcome measures, which is of relatively limited significance in terms of clinical implementation. There was evidence in favour of some conservative interventions, but these findings need to be confirmed by larger, well-designed controlled trials, which should include evaluation of the acceptability of the intervention to patients and the effect on their quality of life.}, }
@article {pmid39468666, year = {2024}, author = {Lian, J and Xia, L and Wang, G and Wu, W and Yi, P and Li, M and Su, X and Chen, Y and Li, X and Dou, F and Wang, Z}, title = {Multi-omics evaluation of clinical-grade human umbilical cord-derived mesenchymal stem cells in synergistic improvement of aging related disorders in a senescence-accelerated mouse model.}, journal = {Stem cell research &amp; therapy}, volume = {15}, number = {1}, pages = {383}, pmid = {39468666}, issn = {1757-6512}, support = {3502220214001//Xiamen Cell Therapy Research Center/ ; 3502Z20234008//Key Healthcare Projects of Xiamen City/ ; 202212631066//Xiamen Medical College Undergraduate Innovation and Entrepreneurship Training Program/ ; 2022//Xiamen Medical College Undergraduate Innovation and Entrepreneurship Training Program/ ; 2023QNB003//Health science and technology project of Fujian Province/ ; 3502Z202372072//Natural Science Foundation of Xiamen/ ; 3502Z20244ZD1009//Natural Science Foundation of Xiamen/ ; }, mesh = {Animals ; Mice ; *Mesenchymal Stem Cells/metabolism/cytology ; Humans ; *Umbilical Cord/cytology/metabolism ; *Aging ; *Disease Models, Animal ; Mesenchymal Stem Cell Transplantation/methods ; Gastrointestinal Microbiome ; Male ; DNA Damage ; Multiomics ; }, abstract = {BACKGROUND: The prevalence of age-related disorders, particularly in neurological and cardiovascular systems, is an increasing global health concern. Mesenchymal stem cell (MSC) therapy, particularly using human umbilical cord-derived MSCs (HUCMSCs), has shown promise in mitigating these disorders. This study investigates the effects of HUCMSCs on aging-related conditions in a senescence-accelerated mouse model (SAMP8), with a focus on DNA damage, gut microbiota alterations, and metabolic changes.<br><br>METHODS: SAMP8 mice were treated with clinical-grade HUCMSCs via intraperitoneal injections. Behavioral and physical assessments were conducted to evaluate cognitive and motor functions. The Single-Strand Break Mapping at Nucleotide Genome Level (SSiNGLe) method was employed to assess DNA single-strand breaks (SSBs) across the genome, with particular attention to exonic regions and transcription start sites. Gut microbiota composition was analyzed using 16S rRNA sequencing, and carboxyl metabolomic profiling was performed to identify changes in circulating metabolites.<br><br>RESULTS: HUCMSC treatment significantly improved motor coordination and reduced anxiety in SAMP8 mice. SSiNGLe analysis revealed a notable reduction in DNA SSBs in MSC-treated mice, especially in critical genomic regions, suggesting that HUCMSCs may mitigate age-related DNA damage. The functional annotation of the DNA breaktome indicated a potential link between reduced DNA damage and altered metabolic pathways. Additionally, beneficial alterations in gut microbiota were observed, including an increase in short-chain fatty acid (SCFA)-producing bacteria, which correlated with improved metabolic profiles.<br><br>CONCLUSION: The administration of HUCMSCs in SAMP8 mice not only reduces DNA damage but also induces favorable changes in gut microbiota and metabolism. The observed alterations in DNA break patterns, along with specific changes in microbiota and metabolic profiles, suggest that these could serve as potential biomarkers for evaluating the efficacy of HUCMSCs in treating age-related disorders. This highlights a promising avenue for the development of new therapeutic strategies that leverage these biomarkers, to enhance the effectiveness of HUCMSC-based treatments for aging-associated diseases.}, }
@article {pmid39468065, year = {2024}, author = {Wang, G and Cao, L and Li, S and Zhang, M and Li, Y and Duan, J and Li, Y and Hu, Z and Wu, J and Ni, J and Lan, D and Li, T and Lu, J}, title = {Gut microbiota dysbiosis-mediated ceramides elevation contributes to corticosterone-induced depression by impairing mitochondrial function.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {111}, pmid = {39468065}, issn = {2055-5008}, support = {82371176//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81801331//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Mitochondria/metabolism ; *Corticosterone ; Mice ; *Depression ; *Ceramides/metabolism ; *Dysbiosis ; *Hippocampus/metabolism ; Fecal Microbiota Transplantation ; Male ; Disease Models, Animal ; Feces/microbiology ; Mice, Inbred C57BL ; Neurogenesis ; Behavior, Animal/drug effects ; }, abstract = {The role of gut microbiota (GM) dysbiosis in the pathogenesis of depression has received widespread attention, but the mechanism remains elusive. Corticosterone (CORT)-treated mice showed depression-like behaviors, reduced hippocampal neurogenesis, and altered composition of the GM. Fecal microbial transplantation from CORT-treated mice transferred depression-like phenotypes and their dominant GM to the recipients. Fecal metabolic profiling exposed remarkable increase of gut ceramides in CORT-treated and recipient mice. Oral gavage with Bifidobacterium pseudolongum and Lactobacillus reuteri could induce elevations of gut ceramides in mice. Ceramides-treated mice showed depressive-like phenotypes, significant downregulation of oxidative phosphorylation-associated genes, and hippocampal mitochondrial dysfunction. Our study demonstrated a link between chronic exposure to CORT and its impact on GM composition, which induces ceramides accumulation, ultimately leading to hippocampal mitochondrial dysfunction. This cascade of events plays a critical role in reducing adult hippocampal neurogenesis and is strongly associated with the development of depression-like behaviors.}, }
@article {pmid39467697, year = {2024}, author = {Qu, J and Meng, F and Wang, Z and Xu, W}, title = {Unlocking Cardioprotective Potential of Gut Microbiome: Exploring Therapeutic Strategies.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {12}, pages = {2413-2424}, pmid = {39467697}, issn = {1738-8872}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Prebiotics ; Animals ; Fecal Microbiota Transplantation ; Synbiotics ; Coronary Artery Disease/microbiology/prevention &amp; control ; Bacteria/metabolism/classification ; Anti-Inflammatory Agents ; }, abstract = {The microbial community inhabiting the human gut resembles a bustling metropolis, wherein beneficial bacteria play pivotal roles in regulating our bodily functions. These microorganisms adeptly break down resilient dietary fibers to fuel our energy, synthesize essential vitamins crucial for our well-being, and maintain the delicate balance of our immune system. Recent research indicates a potential correlation between alterations in the composition and activities of these gut microbes and the development of coronary artery disease (CAD). Consequently, scientists are delving into the intriguing realm of manipulating these gut inhabitants to potentially mitigate disease risks. Various promising strategies have emerged in this endeavor. Studies have evidenced that probiotics can mitigate inflammation and enhance the endothelial health of our blood vessels. Notably, strains such as Lactobacilli and Bifidobacteria have garnered substantial attention in both laboratory settings and clinical trials. Conversely, prebiotics exhibit anti-inflammatory properties and hold potential in managing conditions like hypertension and hypercholesterolemia. Synbiotics, which synergistically combine probiotics and prebiotics, show promise in regulating glucose metabolism and abnormal lipid profiles. However, uncertainties persist regarding postbiotics, while antibiotics are deemed unsuitable due to their potential adverse effects. On the other hand, TMAO blockers, such as 3,3-dimethyl-1-butanol, demonstrate encouraging outcomes in laboratory experiments owing to their anti-inflammatory and tissue-protective properties. Moreover, fecal transplantation, despite yielding mixed results, warrants further exploration and refinement. In this comprehensive review, we delve into the intricate interplay between the gut microbiota and CAD, shedding light on the multifaceted approaches researchers are employing to leverage this understanding for therapeutic advancements.}, }
@article {pmid39466773, year = {2024}, author = {Partida-Rodríguez, O and Brown, EM and Woodward, SE and Cirstea, M and Reynolds, LA and Petersen, C and Vogt, SL and Peña-Díaz, J and Thorson, L and Arrieta, MC and Hernández, EG and Rojas-Velázquez, L and Moran, P and González Rivas, E and Serrano-Vázquez, A and Pérez-Juárez, H and Torres, J and Ximénez, C and Finlay, BB}, title = {Fecal microbiota transplantation from protozoa-exposed donors downregulates immune response in a germ-free mouse model, its role in immune response and physiology of the intestine.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0312775}, pmid = {39466773}, issn = {1932-6203}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Mice ; *Germ-Free Life ; Gastrointestinal Microbiome/immunology ; Cytokines/metabolism ; T-Lymphocytes, Regulatory/immunology ; Intestines/immunology/parasitology/microbiology ; Mice, Inbred C57BL ; Intestinal Mucosa/immunology/metabolism ; Down-Regulation ; Female ; Spleen/immunology/metabolism ; }, abstract = {Intestinal parasites are part of the intestinal ecosystem and have been shown to establish close interactions with the intestinal microbiota. However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the immune response of germ-free mice transplanted with fecal microbiota (FMT) from individuals with multiple parasitic protozoans (P) and non-parasitized individuals (NP). We determined the production of intestinal cytokines, the lymphocyte populations in both the colon and the spleen, and the genetic expression of markers of intestinal epithelial integrity. We observed a general downregulation of the intestinal immune response in mice receiving FMT-P. We found significantly lower intestinal production of the cytokines IL-6, TNF, IFN-γ, MCP-1, IL-10, and IL-12 in the FMT-P. Furthermore, a significant decrease in the proportion of CD3+, CD4+, and Foxp3+ T regulatory cells (Treg) was observed in both, the colon and spleen with FMT-P in contrast to FMT-NP. We also found that in FMT-P mice there was a significant decrease in tjp1 expression in all three regions of the small intestine; ocln in the ileum; reg3γ in the duodenum and relmβ in both the duodenum and ileum. We also found an increase in colonic mucus layer thickness in mice colonized with FMT-P in contrast with FMT-NP. Finally, our results suggest that gut protozoa, such as Blastocystis hominis, Entamoeba coli, Endolimax nana, Entamoeba histolytica/E. dispar, Iodamoeba bütschlii, and Chilomastix mesnili consortia affect the immunoinflammatory state and induce functional changes in the intestine via the gut microbiota. Likewise, it allows us to establish an FMT model in germ-free mice as a viable alternative to explore the effects that exposure to intestinal parasites could have on the immune response in humans.}, }
@article {pmid39463943, year = {2024}, author = {Dai, A and Adintori, PA and Funnell, T and Jogia, WP and Fei, T and Waters, NR and Rangesa, M and Ballweg, A and Gipson, B and Raj, S and Hayase, E and Markey, KA and Burgos da Silva, M and Miltiadous, O and Brambilla, CZ and Buchan, ML and Peets, T and Gradissimo, A and Smith, N and Katsamakis, Z and Warren, A and Amoretti, LA and Duan, C and Zhang, C and Matheis, F and Sullivan, AP and Slingerland, JB and Clurman, A and Brereton, DG and Giardina, PA and Gomes, ALC and Johnson, AJ and Knights, D and Jenq, RR and Perales, MA and Giralt, SA and Schluter, J and van den Brink, MRM and Peled, J}, title = {Sugar-rich foods exacerbate antibiotic-induced microbiome injury.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.10.14.617881}, pmid = {39463943}, issn = {2692-8205}, abstract = {Intestinal microbiota composition is implicated in several diseases; understanding the factors that influence it are key to elucidating host-commensal interactions and to designing microbiome-targeted therapies. We quantified how diet influences microbiome dynamics in hospitalized patients. We recorded 9,419 meals consumed by 173 patients undergoing hematopoietic cell transplantation and profiled the microbiome in 1,009 longitudinally collected stool samples from 158 of them. Caloric intake was correlated with fecal microbiota diversity. Bayesian inference revealed associations between intake of sweets or sugars during antibiotic exposure with microbiome disruption, as assessed by low diversity or expansion of the pathobiont Enterococcus. We validated this observation experimentally, finding that sucrose exacerbated antibiotic-induced Enterococcus expansion in mice. Taken together, our results suggest that avoiding sugar-rich foods during antibiotic treatment may reduce microbiome injury.}, }
@article {pmid39462615, year = {2024}, author = {Ozaki, Y and Suzuki, Y and Suzuki, H}, title = {[Gut Microbiota as a Potential Biomarker for Immune Checkpoint Inhibitors].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {51}, number = {9}, pages = {862-864}, pmid = {39462615}, issn = {0385-0684}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use ; *Lung Neoplasms/drug therapy/immunology/microbiology ; Biomarkers, Tumor/immunology ; }, abstract = {Immune checkpoint inhibitors(ICIs)currently play a predominant role in the standard treatment of non-small cell lung cancer(NSCLC)across all stages. While PD-L1 positivity has traditionally been used as the sole effective biomarker, evidence suggests that certain efficacy exists even in PD-L1-negative lung cancers. Various investigations have been conducted to identify biomarkers predicting the therapeutic efficacy of ICIs, focusing on both tumor-local and host-related factors. Among indicators reflecting the host status, the gut microbiota has garnered attention, with its composition and diversity potentially influencing the efficacy of ICI therapy. The presence of specific gut microbiota has been frequently reported to enhance the effectiveness of ICI treatment. Furthermore, the use of antibiotics may diminish the effects of ICIs, while fecal microbiota transplantation has shown potential to enhance ICI therapy. In our department, analysis of the gut microbiota in patients receiving anti-PD-1 antibody treatment has been conducted, yielding promising results through the identification of specific bacterial species and the search for these species using real-time PCR, suggesting avenues for further research. Recently, attention has also been drawn to the lung microbiota and tumor microbiota in the context of lung cancer, with reports suggesting that increased diversity in these microbial communities may correlate with the efficacy of ICI therapy. However, none of these findings alone provide sufficient evidence as standalone biomarkers, necessitating future research to advance from both the host environment, including the gut microbiota, and the microenvironment of the tumor site, such as the lung and tumor microbiota.}, }
@article {pmid39462312, year = {2024}, author = {Garcia-Martinez, Y and Alexandrova, E and Iebba, V and Ferravante, C and Spinelli, M and Franci, G and Amoresano, A and Weisz, A and Trepiccione, F and Borriello, M and Ingrosso, D and Perna, AF}, title = {Does gut microbiota dysbiosis impact the metabolic alterations of hydrogen sulfide and lanthionine in patients with chronic kidney disease?.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {436}, pmid = {39462312}, issn = {1471-2180}, support = {Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hydrogen Sulfide/metabolism ; *Renal Insufficiency, Chronic/microbiology/metabolism ; Male ; Female ; Middle Aged ; *Dysbiosis/microbiology ; *Feces/microbiology/chemistry ; Aged ; Sulfides/metabolism ; Adult ; Renal Dialysis ; Bacteria/classification/isolation &amp; purification/metabolism/genetics ; Alanine/analogs &amp; derivatives/metabolism ; Case-Control Studies ; }, abstract = {BACKGROUND: Chronic Kidney Disease (CKD) is characterized by a methionine-related metabolic disorder involving reduced plasma levels of hydrogen sulfide (H2S) and increased lanthionine. The gut microbiota influences methionine metabolism, potentially impacting sulfur metabolite dysfunctions in CKD. We evaluated whether gut microbiota dysbiosis contributes to H2S and lanthionine metabolic alterations in CKD.<br><br>METHODS: The gut microbiota of 88 CKD patients (non-dialysis, hemodialysis, and transplant patients) and 26 healthy controls were profiled using 16&#xa0;S-amplicon sequencing. H2S and lanthionine concentrations were measured in serum and fecal samples using the methylene blue method and LC-MS/MS, respectively.<br><br>RESULTS: The CKD population exhibited a tenfold increase in serum lanthionine associated with kidney dysfunction. Despite lanthionine retention, hemodialysis and transplant patients had significantly lower serum H2S than healthy controls. Fecal H2S levels were not altered or related to bloodstream H2S concentrations. Conversely, fecal lanthionine was significantly increased in CKD compared to healthy controls and associated with kidney dysfunction. Microbiota composition varied among CKD groups and healthy controls, with the greatest dissimilarity observed between hemodialysis and transplant patients. Changes relative to the healthy group included uneven Ruminococcus gnavus distribution (higher in transplant patients and lower in non-dialysis CKD patients), reduced abundance of the short-chain fatty acid-producing bacteria Alistipes indistinctus and Coprococcus eutactus among transplant patients, and depleted Streptococcus salivarius in non-dialysis CKD patients. A higher abundance of Methanobrevibacter smithii, Christensenella minuta, and Negativibacillus massiliensis differentiated hemodialysis patients from controls. No correlation was found between differentially abundant species and the metabolic profile that could account for the H2S and lanthionine alterations observed.<br><br>CONCLUSIONS: The metabolic deregulation of H2S and lanthionine observed in the study was not associated with alterations in the gut microbiota composition in CKD patients. Further research on microbial sulfur pathways may provide a better understanding of the role of gut microbiota in maintaining H2S and lanthionine homeostasis.}, }
@article {pmid39462039, year = {2024}, author = {Zhou, X and Shen, S and Wang, Z}, title = {Genetic evidence of bidirectional mendelian randomization study on the causality between gut microbiome and respiratory diseases contributes to gut-lung axis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {25550}, pmid = {39462039}, issn = {2045-2322}, support = {82174302//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/genetics ; *Genome-Wide Association Study ; Lung/microbiology/pathology ; Respiratory Tract Diseases/microbiology/genetics ; Risk Factors ; }, abstract = {Observational studies and clinical trials have suggested the relationship between the gut microbiome and respiratory diseases, but the causality between them remains unclear. Firstly, we selected eight respiratory diseases Genome-wide association study (GWAS) datasets mainly from the FinnGen collaboration as outcomes. The exposure was based on GWAS statistics about the gut microbiome, sourced from the MiBioGen consortium, including gut microbial taxa. The causal link between the gut microbiome and respiratory illnesses was then estimated using a Two-sample Mendelian randomization (MR) analysis, including the inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. To ensure reliability, F-statistics and sensitivity tests were conducted. Furthermore, we performed a reverse MR analysis of the pre-Mendelian positive findings to possible reverse causality. For the 196 gut microbe taxa, the IVW analysis suggested 88 potential associations with eight clinically prevalent respiratory diseases. Among them, 30 causal associations were found in more than one MR method. Multiple statistical corrections have confirmed three causal associations: genus Holdemanella was a risk factor for chronic obstructive pulmonary disease (COPD) (P = 1.3 × 10[-4], OR = 1.18), family FamilyXIII was a protective factor for COPD (P = 1.3 × 10[-3], OR = 0.75), and genus Oxalobacter was a risk factor for asthma (P = 2.1 × 10[-4], OR = 1.09). Our MR analysis results indicate that there would be a causal relationship between the gut microbiome and respiratory diseases, contributing to the gut-lung axis. This finding offers new insights into the gut microbiome's roles in respiratory diseases' clinical prevention, pathogenesis, and improvement of clinical symptoms. Further randomized controlled trials are necessary to clarify the protective effect of probiotics and fecal microbial transplantation on respiratory health.}, }
@article {pmid39461459, year = {2024}, author = {Attauabi, M and Madsen, GR and Bendtsen, F and Seidelin, JB and Burisch, J}, title = {Multidimensional Patient-Reported Outcomes and Quality of Life at Diagnosis of IBD: A Population-Based Inception Cohort Study.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2024.08.047}, pmid = {39461459}, issn = {1542-7714}, abstract = {BACKGROUND AND AIMS: Patient-reported outcomes (PROs) are pivotal in assessing treatment efficacy and estimating the burden of inflammatory bowel diseases (IBDs). We investigated PROs at the time of IBD diagnosis.<br><br>METHODS: The Short Inflammatory Bowel Disease Questionnaire (SIBDQ), IBD Disability Index (IBD-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and disease activity-related PROs were assessed in the Copenhagen IBD Inception Cohort, a prospective, population-based cohort of patients newly diagnosed with IBD between May 2021 and May&#xa0;2023.<br><br>RESULTS: A total of 203 ulcerative colitis (UC) and 116 Crohn's disease (CD) patients were recruited. At diagnosis, 160 (78.8%) and 99 (85.3%) patients with UC and CD, respectively, reported moderate-to-severe impairment in at least 1 PRO (P&#xa0;= .18), with 89 (43.8%) and 74 (63.8%), respectively, reporting moderate-to-severe impairment in at least 2 PROs (P < .01). Being female, the disease extent of UC, and extraintestinal manifestations were associated with impaired PROs. There were no differences found according to CD phenotype. FACIT-F, IBD-DI, and SIBDQ scores showed weak, but significant, correlations with the Mayo endoscopic score in UC, and the FACIT-F score with C-reactive protein. In CD, SIBDQ, IBD-DI, and FACIT-F correlated moderately with C-reactive protein and fecal calprotectin but not with the endoscopic severity of CD. None of the PROs correlated with iron, ferritin, or vitamin D levels. Among the most prevalent symptoms reported were fatigue, abdominal pain, urgency, and passing of blood in both CD and UC.<br><br>CONCLUSIONS: We found a substantial patient-reported disease burden in newly diagnosed IBD, underscoring the importance of vigilant PRO monitoring in clinical practice.}, }
@article {pmid39461299, year = {2024}, author = {Verbiest, A and Hvistendahl, MK and Bolognani, F and Li, C and Youssef, NN and Huh, S and Menys, A and Bhatnagar, G and Vanslembrouck, R and Peeters, R and Sartoris, R and Vermeersch, P and Wauters, L and Verbeke, K and Jeppesen, PB and Joly, F and Vanuytsel, T}, title = {Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon-in-continuity: A multicenter, open-label, metabolic balance study.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {12}, pages = {158-166}, doi = {10.1016/j.clnu.2024.10.011}, pmid = {39461299}, issn = {1532-1983}, mesh = {Humans ; Male ; Female ; *Short Bowel Syndrome/drug therapy ; Middle Aged ; Adult ; Treatment Outcome ; Aged ; Colon/drug effects ; Intestinal Failure/drug therapy ; Intestinal Absorption/drug effects ; }, abstract = {BACKGROUND: Apraglutide is a novel long-acting GLP-2 analog in development for short bowel syndrome with intestinal failure (SBS-IF). This multicenter, open-label, phase 2 study in SBS-IF and colon-in-continuity (CiC) investigates the safety and efficacy of apraglutide.<br><br>METHODS: This was a 52-week phase 2 metabolic balance study (MBS) in 9 adult patients with SBS-IF-CiC receiving once-weekly subcutaneous apraglutide injections. Safety was the primary endpoint. Secondary endpoints included changes in absorption parameters (MBS at baseline, after 4 weeks with stable parenteral support (PS), and 48 weeks), PS needs (48-week PS adjustment period based on monthly 48-h fluid balances) and intestinal morphology and motility (static and cine MRI at baseline and 4, 24 and 48 weeks).<br><br>RESULTS: PS volume decreased by&#xa0;-4702&#xa0;mL/week (-52&#xa0;%; p&#xa0;<&#xa0;0.001) at week 52. Seven patients (78&#xa0;%) achieved &#x2265;1 day off PS at week 52. At 4 weeks, fecal output was reduced by 253&#xa0;g/day (p&#xa0;=&#xa0;0.013). At 48 weeks, increases in wet weight absorption by 316&#xa0;g/day (p&#xa0;=&#xa0;0.039), energy absorption by 1134&#xa0;kJ/day (p&#xa0;=&#xa0;0.041) and carbohydrate absorption by 56.1&#xa0;g/day (p&#xa0;=&#xa0;0.024) were observed. Moreover, small bowel length increased from 29.7 to 40.7&#xa0;cm (p&#xa0;=&#xa0;0.012), duodenal wall thickness increased by 0.8&#xa0;mm (p&#xa0;=&#xa0;0.02) and motility in the proximal colon was reduced (p&#xa0;=&#xa0;0.031). A total of 127 adverse events was reported, which were mostly mild to moderate.<br><br>CONCLUSION: Apraglutide had an acceptable safety profile and was associated with significant reductions in PS needs and days off PS, improvements in intestinal absorption, and structural and functional intestinal changes in patients with SBS-IF-CiC.<br><br>CLINICALTRIALS: gov, Number NCT04964986.}, }
@article {pmid39460926, year = {2025}, author = {Magnusson, C and Ölfvingsson, E and Hjortswang, H and Östholm, &#xc5; and Serrander, L}, title = {Improved health-related quality of life in patients with recurrent Clostridioides difficile infection after treatment with faecal microbiota transplantation.}, journal = {Infectious diseases (London, England)}, volume = {57}, number = {3}, pages = {239-246}, doi = {10.1080/23744235.2024.2415694}, pmid = {39460926}, issn = {2374-4243}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Quality of Life ; *Clostridium Infections/therapy ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Recurrence ; Clostridioides difficile ; Surveys and Questionnaires ; Adult ; Treatment Outcome ; }, abstract = {BACKGROUND: Clostridioides difficile is a major burden for both healthcare systems and the patients. Faecal microbiota transplantation (FMT) is becoming more common as a treatment since it reduces the risk of recurrent Clostridioides difficile infection (rCDI).<br><br>OBJECTIVES: To evaluate how treatment with FMT is affecting the health-related quality of life (HRQoL) in patients with rCDI.<br><br>METHODS: A prospective observational cohort study was conducted where patients who were offered FMT as a treatment for rCDI were asked to fill in a questionnaire based on the Short Health Scale (SHS) and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) about their HRQoL before and after treatment.<br><br>RESULTS: Patients with rCDI had poor HRQoL, which improved following FMT.<br><br>CONCLUSIONS: Since FMT cures, reduces the risk of new recurrences of CDI and improves the HRQoL of the patients, it should be offered as a treatment for patients with rCDI. Also, SHS is a useful and reliable instrument for measuring HRQoL in patients with rCDI.}, }
@article {pmid39460538, year = {2024}, author = {Yang, J and Liang, J and Hu, N and He, N and Liu, B and Liu, G and Qin, Y}, title = {The Gut Microbiota Modulates Neuroinflammation in Alzheimer's Disease: Elucidating Crucial Factors and Mechanistic Underpinnings.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {30}, number = {10}, pages = {e70091}, pmid = {39460538}, issn = {1755-5949}, support = {2024yjscx013//Innovative Research Project for Postgraduate Students of Heilongjiang University of Traditional Chinese Medicine/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Alzheimer Disease/microbiology/metabolism/pathology ; Humans ; *Neuroinflammatory Diseases/microbiology/metabolism ; Animals ; Dysbiosis ; Blood-Brain Barrier/metabolism/microbiology ; Fecal Microbiota Transplantation ; Probiotics ; }, abstract = {BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuronal loss, commonly linked to amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Recent research highlights the gut microbiota as a key player in modulating neuroinflammation, a critical pathological feature of AD. Understanding the role of the gut microbiota in this process is essential for uncovering new therapeutic avenues and gaining deeper insights into AD pathogenesis.<br><br>METHODS: This review provides a comprehensive analysis of how gut microbiota influences neuroinflammation and glial cell function in AD. A systematic literature search was conducted, covering studies from 2014 to 2024, including reviews, clinical trials, and animal studies. Keywords such as "gut microbiota," "Alzheimer's disease," "neuroinflammation," and "blood-brain barrier" were used.<br><br>RESULTS: Dysbiosis, or the imbalance in gut microbiota composition, has been implicated in the modulation of key AD-related mechanisms, including neuroinflammation, blood-brain barrier integrity, and neurotransmitter regulation. These disruptions may accelerate the onset and progression of AD. Additionally, therapeutic strategies targeting gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, show promise in modulating AD pathology.<br><br>CONCLUSIONS: The gut microbiota is a pivotal factor in AD pathogenesis, influencing neuroinflammation and disease progression. Understanding the role of gut microbiota in AD opens avenues for innovative diagnostic, preventive, and therapeutic strategies.}, }
@article {pmid39459579, year = {2024}, author = {Alswat, AS}, title = {The Influence of the Gut Microbiota on Host Health: A Focus on the Gut-Lung Axis and Therapeutic Approaches.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {39459579}, issn = {2075-1729}, abstract = {The human gut microbiota is a complex ecosystem harboring thousands of microbial strains that play a crucial role in maintaining the overall well-being of its host. The composition of the gut microbiota varies with age from infancy to adulthood and is influenced by dietary habits, environment, and genetic disposition. Recent advances in culture-independent techniques and nucleic acid sequencing have improved our understanding of the diversity of the gut microbiota. The microbial species present in the gut release short-chain fatty acids (SCFAs), which have anti-inflammatory properties. The gut microbiota also plays a substantial role in modulating the host's immune system, promoting immune tolerance, and maintaining homeostasis. The impact of the gut microbiota on the health of the host is quite evident, as gut dysbiosis has been linked to various diseases, including metabolic disorders, autoimmune diseases, allergies, and inflammatory bowel diseases. The gut microbiota has bidirectional communication with the respiratory system, creating the gut-lung axis, which has been associated with different respiratory diseases. Therapeutic approaches targeting the gut microbiota, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), aim to restore microbial balance and promote the growth of beneficial strains in the gut. Nonetheless, gaining knowledge of the complex interactions between the gut microbiota and the host is necessary to develop personalized medicine approaches and microbiota-based therapies for various conditions. This review summarizes studies related to the gut-lung axis with particular emphasis on the role of the microbiota. Future research directions are also discussed.}, }
@article {pmid39458553, year = {2024}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {Nutritional and Microbial Strategies for Treating Acne, Alopecia, and Atopic Dermatitis.}, journal = {Nutrients}, volume = {16}, number = {20}, pages = {}, pmid = {39458553}, issn = {2072-6643}, mesh = {Humans ; *Dermatitis, Atopic/therapy/microbiology ; *Gastrointestinal Microbiome ; *Acne Vulgaris/therapy/microbiology ; *Probiotics/therapeutic use/administration &amp; dosage ; *Alopecia/therapy/microbiology ; Synbiotics/administration &amp; dosage ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Diet ; Skin/microbiology ; }, abstract = {BACKGROUND/OBJECTIVES: Diet is one of the major determinants of the composition and function of the gut microbiome, and diverse studies have established directional connections between gut microbiome dysbiosis and skin dyshomeostasis. Furthermore, a significant link between the gut and certain skin-related disorders has been reported. This work reviews the mechanisms underlying the relationship between nutritional factors, gut microbiome, and certain skin diseases such as acne vulgaris, alopecia, and atopic dermatitis. In addition, it explores how the modulation of the gut microbiome and human skin through diet and various microbial strategies, including probiotics, synbiotics, postbiotics, and fecal microbiota transplantation, may serve as future treatments for skin diseases, possibly replacing traditional methods such as antibiotic, topical corticosteroid, and laser therapies.<br><br>RESULTS: The adequate intake of certain foods can promote a balanced gut microbiome, potentially reducing skin inflammation and improving overall skin health, while poor dietary choices may lead to worse outcomes by disrupting gut homeostasis. In this regard, diets high in antioxidants, fiber, and phytonutrients appear to be beneficial for enhancing skin health and preventing associated comorbidities. In addition, the administration of probiotics, synbiotics, and postbiotics in the treatment of cutaneous diseases has been shown to restore skin dyshomeostasis and to improve the symptoms of the reviewed skin conditions.<br><br>CONCLUSIONS: Consuming a healthy, plant-based diet can reduce skin inflammation and enhance overall skin health. Although the application of probiotics, synbiotics, and postbiotics has demonstrated promise in modulating inflammation, enhancing tissue regeneration, and inhibiting pathogenic colonization, further research is required.}, }
@article {pmid39458486, year = {2024}, author = {Gómez-Pérez, AM and Muñoz-Garach, A and Lasserrot-Cuadrado, A and Moreno-Indias, I and Tinahones, FJ}, title = {Microbiota Transplantation in Individuals with Type 2 Diabetes and a High Degree of Insulin Resistance.}, journal = {Nutrients}, volume = {16}, number = {20}, pages = {}, pmid = {39458486}, issn = {2072-6643}, support = {PI15/011114//Instituto de Salud Carlos III/ ; EPIGEN-MICROBIOTA NCT05076656, PI15/01114//CIBER Fisiopatolog&#xed;a de la Obesidad y Nutrici&#xf3;n (CIBEROBN) and Fondo de Investigaci&#xf3;n para la Salud/ ; CPII21/00013//Instituto de Salud Carlos III-FEDER: Miguel Servet II programm/ ; B-0033-2014//Servicio Andaluz de Salud/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/therapy/blood/microbiology ; Female ; Male ; *Insulin Resistance ; Middle Aged ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Aged ; *Blood Glucose/metabolism ; Single-Blind Method ; Glucose Tolerance Test ; Gastrointestinal Microbiome ; Insulin/blood ; Body Mass Index ; Lactobacillus delbrueckii ; Treatment Outcome ; Glycated Hemoglobin/metabolism ; }, abstract = {The objective of this study was to determine the results of fecal microbiota transplantation (FMT) from healthy lean subjects in patients with type 2 diabetes (T2D); Methods: We designed a phase II, randomized, single-blind, parallel-arm clinical trial. Twenty-one subjects (12 men [57.1%] and 9 women [42.9%]), who had previously signed an informed consent were randomized to FMT from lean donors, a probiotic (Lactobacillus delbrueckii spp. bulgaricus LB-14), or placebo. Mean age at baseline was 62.5 ± 5.8 years and mean body mass index (BMI) at baseline was approximately 32.4 ± 2.4 kg/m[2]. Anthropometric measures, biochemical variables, oral glucose tolerance test (OGTT), and a stool microbiota analysis were performed (baseline, 4 and 12 weeks). The trial was conducted following the Declaration of Helsinki, Good Clinical Practice Guides (CPMP/ICH/135/95) and the current Spanish legislation regarding clinical trials (RD 223/2004).; Results: FMT changes occurred at the expense of the species found in the donor. No differences in weight, body mass index, HbA1c, or the results of the OGTT for glucose and insulin were found between groups after the intervention, although a decrease in uric acid was observed in the probiotic group (-0.5 mg/dL; p = 0.037) and a mild increase in HbA1c in the FMT group (+0.25%; p = 0.041); Conclusions: In our sample, neither FMT from healthy and lean donors nor a probiotic were effective in improving insulin sensitivity and HbA1c in patients with T2D.}, }
@article {pmid39458368, year = {2024}, author = {Marsiglia, R and Pane, S and Del Chierico, F and Russo, A and Vernocchi, P and Romani, L and Cardile, S and Diamanti, A and Galli, L and Tamborino, A and Terlizzi, V and De Angelis, P and Angelino, G and Putignani, L}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infections in a Cystic Fibrosis Child Previously Screen Positive, Inconclusive Diagnosis (CFSPID): A Case Report.}, journal = {Microorganisms}, volume = {12}, number = {10}, pages = {}, pmid = {39458368}, issn = {2076-2607}, support = {Current Research funds//Italian Ministry of Health/ ; }, abstract = {Clostridioides difficile infection (CDI) is generally treated with vancomycin, metronidazole or fidaxomicin, although fecal microbiota transplantation (FMT) represents a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults. In pediatric cystic fibrosis (CF) patients, CDIs are generally asymptomatic and respond to treatment. Here, we present the case of an 8-year-old female, initially diagnosed as "CFTR-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis" (CMRS/CFSPID), who then progressed to CF at 12 months. In the absence of CF-related symptoms, she presented multiple and disabling episodes of bloody diarrhoea with positive tests for C. difficile antigen and A/B toxin. After conventional treatments failed and several CDI relapses, FMT was proposed. Donor screening and GM donor-receiver matching identified her mother as a donor. Metataxonomy and targeted metabolomics provided, through a pre- and post-FMT time course, gut microbiota (GM) profiling to assess GM engraftment. At first, the GM map revealed severe dysbiosis, with a prevalence of Bacteroidetes and Proteobacteria (i.e., Klebsiella spp., Escherichia coli), a reduction in Firmicutes, a GM nearly entirely composed of Enterococcaceae (i.e., Enterococcus) and an almost complete depletion of Verrucomicrobia and Actinobacteria, mostly represented by Veillonella dispar. Post FMT, an increment in Bifidobacterium spp. and Collinsella spp. with a decrease in V. dispar restored intestinal eubiosis. Consistently, four weeks after FMT treatment, the child's gut symptoms cleared, without CDI recurrence.}, }
@article {pmid39458032, year = {2024}, author = {Piccioni, A and Spagnuolo, F and Candelli, M and Voza, A and Covino, M and Gasbarrini, A and Franceschi, F}, title = {The Gut Microbiome in Sepsis: From Dysbiosis to Personalized Therapy.}, journal = {Journal of clinical medicine}, volume = {13}, number = {20}, pages = {}, pmid = {39458032}, issn = {2077-0383}, abstract = {Sepsis is a complex clinical syndrome characterized by an uncontrolled inflammatory response to an infection that may result in septic shock and death. Recent research has revealed a crucial link between sepsis and alterations in the gut microbiota, showing that the microbiome could serve an essential function in its pathogenesis and prognosis. In sepsis, the gut microbiota undergoes significant dysbiosis, transitioning from a beneficial commensal flora to a predominance of pathobionts. This transformation can lead to a dysfunction of the intestinal barrier, compromising the host's immune response, which contributes to the severity of the disease. The gut microbiota is an intricate system of protozoa, fungi, bacteria, and viruses that are essential for maintaining immunity and metabolic balance. In sepsis, there is a reduction in microbial heterogeneity and a predominance of pathogenic bacteria, such as proteobacteria, which can exacerbate inflammation and negatively influence clinical outcomes. Microbial compounds, such as short-chain fatty acids (SCFAs), perform a crucial task in modulating the inflammatory response and maintaining intestinal barrier function. However, the role of other microbiota components, such as viruses and fungi, in sepsis remains unclear. Innovative therapeutic strategies aim to modulate the gut microbiota to improve the management of sepsis. These include selective digestive decontamination (SDD), probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT), all of which have shown potential, although variable, results. The future of sepsis management could benefit greatly from personalized treatment based on the microbiota. Rapid and easy-to-implement tests to assess microbiome profiles and metabolites associated with sepsis could revolutionize the disease's diagnosis and management. These approaches could not only improve patient prognosis but also reduce dependence on antibiotic therapies and promote more targeted and sustainable treatment strategies. Nevertheless, there is still limited clarity regarding the ideal composition of the microbiota, which should be further characterized in the near future. Similarly, the benefits of therapeutic approaches should be validated through additional studies.}, }
@article {pmid39457652, year = {2024}, author = {Zhang, J and Gan, H and Duan, X and Li, G}, title = {Targeting the Intestinal Microbiota: A Novel Direction in the Treatment of Inflammatory Bowel Disease.}, journal = {Biomedicines}, volume = {12}, number = {10}, pages = {}, pmid = {39457652}, issn = {2227-9059}, support = {82170617//National Natural Science Foundation of China/ ; }, abstract = {Over the past decade, there has been a rapid increase in the incidence of inflammatory bowel disease. It has been suggested that multifactorial interactions of environmental factors, genetic factors, immune response and intestinal microbiota are involved in the pathogenesis of inflammatory bowel disease. It is widely recognized that the intestinal microbiota are essential for human metabolism, the immune system and pathogen resistance, and are integral to human health. Therefore, the dysbiosis of the microbiota is a critical step leading to intestinal mucosal damage and a key factor in the pathogenesis of inflammatory bowel disease. Regulating the microbiota through interventions such as enteral nutrition, fecal microbiota transplantation, and probiotic supplementation has the potential to prevent or even reverse intestinal dysbiosis, opening up new perspectives for the treatment of inflammatory bowel disease.}, }
@article {pmid39457040, year = {2024}, author = {Mousa, WK and Al Ali, A}, title = {The Gut Microbiome Advances Precision Medicine and Diagnostics for Inflammatory Bowel Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {20}, pages = {}, pmid = {39457040}, issn = {1422-0067}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/diagnosis/genetics ; *Gastrointestinal Microbiome ; *Precision Medicine/methods ; *Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; Metabolomics/methods ; }, abstract = {The gut microbiome emerges as an integral component of precision medicine because of its signature variability among individuals and its plasticity, which enables personalized therapeutic interventions, especially when integrated with other multiomics data. This promise is further fueled by advances in next-generation sequencing and metabolomics, which allow in-depth high-precision profiling of microbiome communities, their genetic contents, and secreted chemistry. This knowledge has advanced our understanding of our microbial partners, their interaction with cellular targets, and their implication in human conditions such as inflammatory bowel disease (IBD). This explosion of microbiome data inspired the development of next-generation therapeutics for treating IBD that depend on manipulating the gut microbiome by diet modulation or using live products as therapeutics. The current landscape of artificial microbiome therapeutics is not limited to probiotics and fecal transplants but has expanded to include community consortia, engineered probiotics, and defined metabolites, bypassing several limitations that hindered rapid progress in this field such as safety and regulatory issues. More integrated research will reveal new therapeutic targets such as enzymes or receptors mediating interactions between microbiota-secreted molecules that drive or modulate diseases. With the shift toward precision medicine and the enhanced integration of host genetics and polymorphism in treatment regimes, the following key questions emerge: How can we effectively implement microbiomics to further personalize the treatment of diseases like IBD, leveraging proven and validated microbiome links? Can we modulate the microbiome to manage IBD by altering the host immune response? In this review, we discuss recent advances in understanding the mechanism underpinning the role of gut microbes in driving or preventing IBD. We highlight developed targeted approaches to reverse dysbiosis through precision editing of the microbiome. We analyze limitations and opportunities while defining the specific clinical niche for this innovative therapeutic modality for the treatment, prevention, and diagnosis of IBD and its potential implication in precision medicine.}, }
@article {pmid39456641, year = {2024}, author = {Wu, M and Tian, C and Zou, Z and Jin, M and Liu, H}, title = {Gastrointestinal Microbiota in Gastric Cancer: Potential Mechanisms and Clinical Applications-A Literature Review.}, journal = {Cancers}, volume = {16}, number = {20}, pages = {}, pmid = {39456641}, issn = {2072-6694}, support = {WJ2023M92//Scientific research project of Hubei Provincial Health Commission/ ; 320.6750.2023-19-7 and 320.6750.2024-10-2//Clinical Research Special Fund of Wu Jieping Medical Foundation/ ; WX23A31//Medical Science Research Fundation of Wuhan/ ; }, abstract = {Emerging evidence highlights the crucial role of gastrointestinal microbiota in the pathogenesis of gastric cancer. Helicobacter pylori (H. pylori) infection stands out as a primary pathogenic factor. However, interventions such as anti-H. pylori therapy, gastric surgeries, immunotherapy, and chronic inflammation significantly remodel the gastric microbiome, implicating a broader spectrum of microorganisms in cancer development. These microbial populations can modulate gastric carcinogenesis through various mechanisms, including sustained chronic inflammation, bacterial genotoxins, alterations in short-chain fatty acids, elevated gastrointestinal bile acids, impaired mucus barrier function, and increased concentrations of N-nitrosamines and lactic acid. The dynamic changes in gut microbiota also critically influence the outcomes of anti-cancer therapies by modifying drug bioavailability and metabolism, thus affecting therapeutic efficacy and side effect profiles. Additionally, the effectiveness of radiotherapy can be significantly impacted by gut microbiota alterations. Novel therapeutic strategies targeting the microbiome, such as dietary interventions, probiotic and synbiotic supplementation, and fecal microbiota transplantation, are showing promise in cancer treatment. Understanding the intricate relationship between the gut microbiota and gastric cancer is essential for developing new, evidence-based approaches to the prevention and treatment of this malignancy.}, }
@article {pmid39455910, year = {2024}, author = {Tang, BB and Su, CX and Wen, N and Zhang, Q and Chen, JH and Liu, BB and Wang, YQ and Huang, CQ and Hu, YL}, title = {FMT and TCM to treat diarrhoeal irritable bowel syndrome with induced spleen deficiency syndrome- microbiomic and metabolomic insights.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {433}, pmid = {39455910}, issn = {1471-2180}, support = {2023ZR004//TCM science and technology project of Zhejiang Province/ ; 2024KY869//Zhejiang Provincial Medical and Health Science and Technology Project/ ; 2022020801020508//Knowledge Innovation Program of Wuhan Shuguang Project/ ; 2022020801020584//Knowledge Innovation Program of Wuhan Shuguang Project/ ; 82374205//National Natural Science Foundation of China/ ; 2020020601012244//Wuhan Applied Foundational Frontier Project/ ; }, mesh = {Animals ; *Irritable Bowel Syndrome/therapy/microbiology/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Fecal Microbiota Transplantation ; *Diarrhea/microbiology/therapy/drug therapy ; *Medicine, Chinese Traditional/methods ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Disease Models, Animal ; *Metabolomics ; Splenic Diseases/therapy/microbiology/drug therapy ; Male ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Spleen/microbiology/metabolism ; }, abstract = {BACKGROUND: Diarrheal irritable bowel syndrome (IBS-D) is a functional bowel disease with diarrhea, and can be associated with common spleen deficiency syndrome of the prevelent traditional Chinese medicine (TCM) syndrome. Fecal microbiota transplantation (FMT) could help treating IBS-D, but may provide variable effects. Our study evaluated the efficacy of TCM- shenling Baizhu decoction and FMT in treating IBS-D with spleen deficiency syndrome, with significant implications on gut microbiome and serum metabolites.<br><br>METHODS: The new borne rats were procured from SPF facility and separated as healthy (1 group) and IBS-D model (3 groups) rats were prepared articially using mother's separation and senna leaf treatment. 2 groups of IBS-D models were further treated with TCM- shenling Baizhu decoction and FMT. The efficacy was evaluated by defecation frequency, bristol stool score, and intestinal tight junction proteins (occludin-1 and claudin-1) expression. Microbiomic analysis was conducted using 16&#xa0;S rRNA sequencing and bioinformatics tools. Metabolomics were detected in sera of rats by LC-MS and annotated by using KEGG database.<br><br>RESULTS: Significant increment in occludin-1 and claudin-1 protein expression alleviated the diarrheal severity in IBS-D rats (P&#x2009;<&#x2009;0.05) after treatment with FMT and TCM. FMT and TCM altered the gut microbiota and regulated the tryptophan metabolism, steroid hormone biosynthesis and glycerophospholipid metabolism of IBS-D rats with spleen deficiency syndrome.The microbial abundance were changed in each case e.g., Monoglobus, Dubosiella, and Akkermansia and othe metabolic profiles.<br><br>CONCLUSION: FMT and TCM treatment improved the intestinal barrier function by regulating gut microbiota and improved metabolic pathways in IBS-D with spleen deficiency syndrome.}, }
@article {pmid39454127, year = {2024}, author = {Ran, X and Li, Y and Guo, W and Li, K and Guo, W and Wang, X and Liu, J and Bi, J and Fu, S}, title = {Angelica sinensis Polysaccharide Alleviates Staphylococcus aureus-Induced Mastitis by Regulating The Intestinal Flora and Gut Metabolites.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {44}, pages = {24504-24517}, doi = {10.1021/acs.jafc.4c06094}, pmid = {39454127}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Female ; Mice ; *Polysaccharides/pharmacology/administration &amp; dosage/chemistry ; *Staphylococcus aureus/drug effects ; *Mastitis/microbiology/drug therapy/metabolism ; *Staphylococcal Infections/microbiology/drug therapy/metabolism ; *Angelica sinensis/chemistry ; Humans ; Bacteria/classification/metabolism/isolation &amp; purification/drug effects/genetics ; Plant Extracts/pharmacology/administration &amp; dosage ; }, abstract = {The modulation of intestinal flora by various polysaccharides has been shown to mitigate disease progression. Recent research reveals a significant link between intestinal flora and the progression of mastitis. This study demonstrates that the oral administration of Angelica sinensis polysaccharide (ASP) reduces mammary inflammation and blood-milk barrier (BMB) damage induced by Staphylococcus aureus in mice, primarily through the modulation of intestinal flora. The beneficial effects of ASP were negated when antibiotics disrupted the gut microbiota in mice. Furthermore, fecal microbiota transplantation (FMT) from ASP-treated mice to recipients markedly alleviated symptoms of S. aureus-induced mastitis. Oral ASP not only enhances gut microbial diversity but also shifts its composition, increasing the abundance of Lachnospiraceae_NK4A136 while reducing Erysipelatoclostridium. Metabolomic analysis revealed that ASP alters intestinal metabolic pathways, elevating levels of metabolites, such as tabersonine and riboflavin. Notably, tabersonine was found to ameliorate S. aureus-induced mastitis. These results suggest that targeting intestinal flora and metabolism through polysaccharides could serve as a promising strategy for mastitis intervention and potentially for other infectious diseases, as well.}, }
@article {pmid39452187, year = {2024}, author = {Niyazi, D and Vergiev, S and Markovska, R and Stoeva, T}, title = {Prevalence and Molecular Epidemiology of Intestinal Colonization by Multidrug-Resistant Bacteria among Hematopoietic Stem-Cell Transplantation Recipients: A Bulgarian Single-Center Study.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {10}, pages = {}, pmid = {39452187}, issn = {2079-6382}, support = {19019/2019//Medical University of Varna/ ; }, abstract = {Background/Objectives: Intestinal colonization by multidrug-resistant (MDR) bacteria is considered one of the main risk factors for invasive infections in the hematopoietic stem-cell transplant (HSCT) setting, associated with hard-to-eradicate microorganisms. The aim of this study was to assess the rate of intestinal colonization by MDR bacteria and their microbial spectrum in a group of post-HSCT patients to study the genetic determinants of beta-lactam and glycopeptide resistance in the recovered isolates, as well as to determine the epidemiological relation between them. Methods: The intestinal colonization status of 74 patients admitted to the transplantation center of University Hospital "St. Marina"-Varna in the period January 2019 to December 2021 was investigated. Stool samples/rectal swabs were screened for third-generation cephalosporin and/or carbapenem-resistant Gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Stenotrophomonas maltophilia. Identification and antimicrobial susceptibility testing were performed by Phoenix (BD, Sparks, MD, USA) and MALDI Biotyper sirius (Bruker, Bremen, Germany). Molecular genetic methods (PCR, DNA sequencing) were used to study the mechanisms of beta-lactam and glycopeptide resistance in the collected isolates, as well as the epidemiological relationship between them. Results: A total of 28 patients (37.8%) were detected with intestinal colonization by MDR bacteria. Forty-eight non-duplicate MDR bacteria were isolated from their stool samples. Amongst them, the Gram-negative bacteria prevailed (68.8%), dominated by ESBL-producing Escherichia coli (30.3%), and followed by carbapenem-resistant Pseudomonas sp. (24.2%). The Gram-positive bacteria were represented exclusively by Enterococcus faecium (31.2%). The main beta-lactam resistance mechanisms were associated with CTX-M and VIM production. VanA was detected in all vancomycin-resistant enterococci. A clonal relationship was observed among Enterobacter cloacae complex and among E. faecium isolates. Conclusions: To the best of our knowledge, this is the first Bulgarian study that presents detailed information about the prevalence, resistance genetic determinants, and molecular epidemiology of MDR gut-colonizing bacteria in HSCT patients.}, }
@article {pmid39449276, year = {2024}, author = {Zhang, H and Luo, M and Li, Y and Liu, L and Bian, J and Gong, L and He, C and Han, L and Wang, M}, title = {Ellagic acid ameliorates alcohol-induced cognitive and social dysfunction through the gut microbiota-mediated CCL21-CCR7 axis.}, journal = {Food &amp; function}, volume = {15}, number = {22}, pages = {11186-11205}, doi = {10.1039/d4fo03985h}, pmid = {39449276}, issn = {2042-650X}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Ellagic Acid/pharmacology ; Animals ; Mice ; Male ; *Cognitive Dysfunction/drug therapy ; Mice, Inbred C57BL ; Receptors, CCR7/metabolism/genetics ; Ethanol ; Disease Models, Animal ; Signal Transduction/drug effects ; }, abstract = {Chronic alcohol consumption disrupts the balance of the gut microbiome, resulting in alcohol-induced cognitive and social dysfunction (AICSD), and serves as a primary etiological factor for early-onset dementia. Ellagic acid (EA) is a polyphenolic compound belonging to the ellagitannin family, showing potential as a dietary intervention for alleviating cognitive impairments. Nonetheless, the protective effects and underlying mechanisms of EA on AICSD remain unclear. In our study, we employed a multi-omics approach to elucidate the microbiome-mediated mechanism underlying the beneficial effects of EA on AICSD. Firstly, our findings demonstrate that EA significantly ameliorated cognitive and social behavioral deficits as well as neuroinflammation induced by alcohol. Moreover, RNA-seq analysis of hippocampi indicates that EA regulated the KEGG pathway of cytokine-cytokine receptor interaction signaling by downregulating the CCL21-CCR7 axis. Furthermore, we observed that EA effectively restored the dysbiosis of gut microbiota and their derived metabolites induced by chronic alcohol consumption. Strong connections were observed between EA-regulated genes, microbiota and metabolites. Finally, the causal relationship between the microbiome and behavioral changes was further confirmed through antibiotic treatment and fecal microbiota transplantation experiments. Overall, our study provides innovative evidence supporting the role of EA in improving AICSD via regulation of the cytokine-cytokine receptor interaction signaling pathway through the microbiota-mediated CCl21-CCR7 axis. These findings offer valuable insights into both EA-based interventions as well as microbial interventions against AICSD.}, }
@article {pmid39449261, year = {2024}, author = {Lee, JW and Kim, N}, title = {[Efficacy of Fecal Microbial Transplantation for Improving Symptoms of Irritable Bowel Syndrome - A Pilot Study for Voluntary Participants in Korea].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {84}, number = {4}, pages = {168-176}, doi = {10.4166/kjg.2024.107}, pmid = {39449261}, issn = {2233-6869}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/diagnosis ; *Fecal Microbiota Transplantation ; Male ; Female ; Adult ; Middle Aged ; Pilot Projects ; Surveys and Questionnaires ; Republic of Korea ; Severity of Illness Index ; Treatment Outcome ; Feces/microbiology ; }, abstract = {BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a chronic, intractable functional disease. It is inferred that fecal microbiota transplantation (FMT) may have favorable efficacy on IBS by gut microbial modification. The aim of this study was to investigate the efficacy of FMT for improving severity in patients with IBS.<br><br>METHODS: Patients who voluntarily wanted FMT were consecutively enrolled. The study subjects were classified by subtype of IBS by the ROME IV criteria. The IBS-symptom severity score (IBS-SSS) was used to evaluate the efficacy of FMT. The subjects completed a questionnaire at baseline week 0 and weeks 4, 12, and 24 after FMT. FMT was performed by esophagogastroduodenoscopy using frozen stock stool solution. If the follow-up IBS-SSS achieved less than 75 points, it was defined as remission. Adverse events were also gathered.<br><br>RESULTS: Twenty-one subjects were included from October 2023 until July 2024. There were 7 patients with IBS-C, 10 patients with IBS-D, 2 patients with IBS-M, and 2 patients with IBS-U type. The mean SSS of the IBS-D group was 244.0&#xb1;64.2, which was higher than IBS-C group (192.9&#xb1;85.4). Alleviations in IBS-SSS after FMT were observed in 19 subjects (19/21, 90.5%) at week 4. At week 12, 71.4% (5/7) in the IBS-C group and 20.0% (2/10) in the IBS-D group achieved remission. The remission states were maintained up to week 24 and no serious adverse events were reported.<br><br>CONCLUSIONS: FMT might be an effective treatment option for improving symptoms of mild to moderate IBS, especially IBS-C.}, }
@article {pmid39449004, year = {2024}, author = {Munoz-Pinto, MF and Candeias, E and Melo-Marques, I and Esteves, AR and Maranha, A and Magalhães, JD and Carneiro, DR and Sant'Anna, M and Pereira-Santos, AR and Abreu, AE and Nunes-Costa, D and Alarico, S and Tiago, I and Morgadinho, A and Lemos, J and Figueiredo, PN and Januário, C and Empadinhas, N and Cardoso, SM}, title = {Gut-first Parkinson's disease is encoded by gut dysbiome.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {78}, pmid = {39449004}, issn = {1750-1326}, support = {SC01//Cure Parkinson's Trust/ ; PTDC/MED-NEU/3644/2020//Instituto Nacional de Ci&#xea;ncia e Tecnologia de Ci&#xea;ncia Animal/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Parkinson Disease/metabolism/microbiology/immunology ; Mice ; *Dysbiosis/immunology ; Male ; *Mice, Inbred C57BL ; Humans ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: In Parkinson's patients, intestinal dysbiosis can occur years before clinical diagnosis, implicating the gut and its microbiota in the disease. Recent evidence suggests the gut microbiota may trigger body-first Parkinson Disease (PD), yet the underlying mechanisms remain unclear. This study aims to elucidate how a dysbiotic microbiome through intestinal immune alterations triggers PD-related neurodegeneration.<br><br>METHODS: To determine the impact of gut dysbiosis on the development and progression of PD pathology, wild-type male C57BL/6 mice were transplanted with fecal material from PD patients and age-matched healthy donors to challenge the gut-immune-brain axis.<br><br>RESULTS: This study demonstrates that patient-derived intestinal microbiota caused midbrain tyrosine hydroxylase positive (TH&#x2009;+) cell loss and motor dysfunction. Ileum-associated microbiota remodeling correlates with a decrease in Th17 homeostatic cells. This event led to an increase in gut inflammation and intestinal barrier disruption. In this regard, we found a decrease in CD4&#x2009;+&#x2009;cells and an increase in pro-inflammatory cytokines in the blood of PD transplanted mice that could contribute to an increase in the permeabilization of the blood-brain-barrier, observed by an increase in mesencephalic Ig-G-positive microvascular leaks and by an increase of mesencephalic IL-17 levels, compatible with systemic inflammation. Furthermore, alpha-synuclein aggregates can spread caudo-rostrally, causing fragmentation of neuronal mitochondria. This mitochondrial damage subsequently activates innate immune responses in neurons and triggers microglial activation.<br><br>CONCLUSIONS: We propose that the dysbiotic gut microbiome (dysbiome) in PD can disrupt a healthy microbiome and Th17 homeostatic immunity in the ileum mucosa, leading to a cascade effect that propagates to the brain, ultimately contributing to PD pathophysiology. Our landmark study has successfully identified new peripheral biomarkers that could be used to develop highly effective strategies to prevent the progression of PD into the brain.}, }
@article {pmid39447641, year = {2024}, author = {Li, YL and Chen, BY and Feng, ZH and Zhou, LJ and Liu, T and Lin, WZ and Zhu, H and Xu, S and Bai, XB and Meng, XQ and Zhang, J and Liu, Y and Pu, J and Jiang, M and Duan, SZ}, title = {Roles of oral and gut microbiota in acute myocardial infarction.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.10.009}, pmid = {39447641}, issn = {2090-1224}, abstract = {INTRODUCTION: The significance of oral/gut microbiota in acute myocardial infarction (AMI) has been increasingly appreciated. However, correlations between oral/gut microbiota and AMI parameter, as well as the key microbiota that may have a crucial function in this process, remain unclear.<br><br>OBJECTIVES: To investigate the composition and structure of oral and gut microbiota associated with AMI and explore the roles of specific bacterial species in the progression of AMI.<br><br>METHODS: We conducted a case-control study with 37 AMI patients and 36 controls. Oral and gut sample were collected and sequenced. Using correlation analysis, we combined bioinformatics data with AMI clinical parameters and obtained heatmaps of correlation coefficients. Additionally, we used antibiotics to eliminate the gut microbiota of C57BL/6J mice, followed by the transplantation of selected bacteria to verify the gut colonization of oral bacteria and their impact on AMI.<br><br>RESULTS: The component of oral and gut microbiota of AMI group showed significant alterations when compared to the control group. 17 salivary genera, 21 subgingival genera, and 8 gut genera in AMI group substantially differed from those in control group. Additionally, 19 genera from saliva, 19 genera from subgingival plaque, and 11 genera from feces substantially correlated with AMI clinical parameters. Orally administrated S.o (Streptococcus oralis subsp. dentisani), S.p (Streptococcus parasanguinis), and S.s (Streptococcus salivarius) were able to colonize in the gut and exacerbate myocardial infarction.<br><br>CONCLUSION: There is a strong correlation between oral/gut microbiota and AMI. Streptococcus spp. is capable to transmit from oral to gut and exacerbate myocardial infarction in mice. Monitoring and control of specific oral microbiota may be an effective new strategy for improving the therapy of AMI.}, }
@article {pmid39445550, year = {2024}, author = {Wu, Q and Li, P and Li, X and Ma, L and Chen, K and Man, S}, title = {Pueraria Extract Ameliorates Alcoholic Liver Disease via the Liver-Gut-Brain Axis: Focus on Restoring the Intestinal Barrier and Inhibiting Alcohol Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {44}, pages = {24449-24462}, doi = {10.1021/acs.jafc.4c05365}, pmid = {39445550}, issn = {1520-5118}, mesh = {*Liver Diseases, Alcoholic/metabolism/drug therapy/genetics/prevention &amp; control ; *Pueraria/chemistry ; Animals ; Male ; *Ethanol ; *Liver/metabolism/drug effects ; *Plant Extracts/chemistry/pharmacology/administration &amp; dosage ; Humans ; *Gastrointestinal Microbiome/drug effects ; Rats ; Brain-Gut Axis/drug effects ; Bacteria/genetics/classification/drug effects/metabolism/isolation &amp; purification ; Intestinal Mucosa/metabolism/drug effects ; Intestines/drug effects/microbiology ; Mice ; Rats, Sprague-Dawley ; }, abstract = {Alcoholic liver disease (ALD) is one of the causes of hepatocellular carcinoma, accompanied by intestinal leakage and microbial changes. Pueraria has protective effects on liver injury. The aim of this study was to investigate the mechanism of pueraria in the treatment of ALD. UPLC-Q/TOF-MS was used to analyze the composition of the pueraria extract (PUE). Acute and chronic ALD models were established to evaluate the antialcoholic and hepatoprotective effects of PUE. As a result, PUE treatment reduced the serum levels of ALT, AST, TC, and TG and inflammatory factors and alleviated liver inflammation and drunk state. PUE decreased the gene expression of ADH1 and the serum level of acetaldehyde (ACH) to inhibit the generation of ACH from ethanol metabolism, increased the gene level of ALDH2 to accelerate the decomposition of ACH, and thereby alleviated liver inflammation and intestinal barrier damage. Meanwhile, 16 S rDNA revealed that PUE altered the microbiota composition, reduced the amount of Proteobacteria and Desulfobacterota, and thus inhibited the generation of lipopolysaccharide and its downstream-like TLR4/MyD88/NF-κB pathway. PUE also increased the abundance of Bacteroides, Ruminococcus, and Prevotella and producted short-chain fatty acids to protect the intestinal wall. Treatment with fecal microbiota transplantation further confirmed that PUE gut microbiota dependently alleviated ALD. Therefore, PUE regulated gut microbiota and inhibited ethanol metabolism to alleviate ALD through the liver-gut-brain axis. It has good prospects in the future.}, }
@article {pmid39444759, year = {2024}, author = {Yaghmaei, H and Bahanesteh, A and Soltanipur, M and Takaloo, S and Rezaei, M and Siadat, SD}, title = {The Role of Gut Microbiota Modification in Nonalcoholic Fatty Liver Disease Treatment Strategies.}, journal = {International journal of hepatology}, volume = {2024}, number = {}, pages = {4183880}, pmid = {39444759}, issn = {2090-3448}, abstract = {One of the most common chronic liver diseases is nonalcoholic fatty liver disease (NAFLD), which affects many people around the world. Gut microbiota (GM) dysbiosis seems to be an influential factor in the pathophysiology of NAFLD because changes in GM lead to fundamental changes in host metabolism. Therefore, the study of the effect of dysbiosis on the pathogenicity of NAFLD is important. European clinical guidelines state that the best advice for people with NAFLD is to lose weight and improve their lifestyle, but only 40% of people can achieve this goal. Accordingly, it is necessary to provide new treatment approaches for prevention and treatment. In addition to dietary interventions and lifestyle modifications, GM modification-based therapies are of interest. These therapies include probiotics, synbiotics, fecal microbiota transplantation (FMT), and next-generation probiotics. All of these treatments have had promising results in animal studies, and it can be imagined that acceptable results will be obtained in human studies as well. However, further investigations are required to generalize the outcomes of animal studies to humans.}, }
@article {pmid39442873, year = {2024}, author = {Wang, R and Chen, RL and Wu, C and Zhang, XC and Wu, WY and Dai, C and Wang, Y and Li, G}, title = {The gut microbiotas with metabolites regulate the protective role of miR-30a-5p in myocardial infarction.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.10.017}, pmid = {39442873}, issn = {2090-1224}, abstract = {INTRODUCTION: Gut microbial homeostasis is closely associated with myocardial infarction (MI). However, little is known about how gut microbiota influences miRNAs-regulated MI.<br><br>OBJECTIVES: This study aims to elucidate the connections between miR-30a-5p, MI, gut microbiota, and gut microbial metabolite-related pathways, to explore potential strategy for preventing and treating MI.<br><br>METHODS: We evaluated the effects of knocking out (KO) or overexpressing (OE) miR-30a-5p on MI by assessing cardiac structure and function, myocardial enzyme levels, and apoptosis. Then, we applied 16S rDNA sequencing and metabolomics to explore how intestinal microecology and its microorganisms affect miR-30a-5p-regulated MI.<br><br>RESULTS: The results showed that KO exacerbated MI, whereas OE improved MI damage, compared to the wild-type (WT) mice. KO exacerbated intestinal barrier structure deterioration and further downregulated the expression of Cloudin-1, Occludin, and ZO-1 in MI mice. 16S rDNA sequencing-analyzed gut microbiome of KO and WT mice found that KO mainly reduced g_Lactobacillus. Transplanting fecal microorganisms from KO mice aggravated MI damage in WT mice. However, administering probiotics (mainly containing Lactobacillus) helped neutralize these damages. Intriguingly, fecal microbiota transplantation from OE mice reduced MI damage. Analysis of intestinal microbial metabolites in KO and WT mice found that KO may mainly affect ABC transporters. ABCC1 was identified as the target of KO-aggravated MI. Furthermore, fecal transplantation microorganisms of MI patients aggravated MI injury in mice and miR-30a-5p and ABCC1 were involved in the process.<br><br>CONCLUSIONS: Our findings demonstrate that miR-30a-5p regulates MI by affecting intestinal microbiota homeostasis and targeting ABCC1. This highlights the critical importance of maintaining a healthy gut microbiota homeostasis in MI management.}, }
@article {pmid39442743, year = {2024}, author = {Bénard, MV and de Goffau, MC and Blonk, J and Hugenholtz, F and van Buuren, J and Paramsothy, S and Kaakoush, NO and D'Haens, GRAM and Borody, TJ and Kamm, MA and Ponsioen, CY}, title = {Gut Microbiota Features in Relation to Fecal Microbiota Transplantation Outcome in Ulcerative Colitis: A Systematic Review and Meta-Analysis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2024.10.001}, pmid = {39442743}, issn = {1542-7714}, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis, yet its efficacy needs improvement. We conducted a comprehensive evaluation of the current literature on microbial factors affecting outcome, as well as a meta-analysis on some of the largest datasets regarding composition.<br><br>METHODS: MEDLINE, Embase, and Cochrane were systematically searched through August 2024 for relevant studies. The quality of studies was analyzed with JBI tools and a composite critical appraisal score. Additionally, species-level data from 2 landmark FMT trials (the Transplantation of Feces in Ulcerative Colitis; Returning Nature's Homeostasis [TURN] and Fecal Microbiota Transplantation for Chronic Active Ulcerative Colitis [FOCUS] trials) were reanalyzed from a compositional perspective.<br><br>RESULTS: Out of 3755 citations identified, 56 met the inclusion criteria, of which 29 fulfilled quality standards. Higher microbial &#x3b1;-diversity, either in donors or recipients (at baseline or following FMT treatment), was associated with better clinical response rates. Engraftment of the donors' microbiota could not be clearly linked with clinical response, possibly because not every donor has an ideal microbiome. Butyrate-producing species from the Lachnospiraceae and Oscillospiraceae families were often related with response, whereas the reverse was true for Fusobacteria, many Proteobacteria, and Ruminococcus gnavus. Compositional analyses showed that clinical response is associated with a shift from a low-diversity, often Bacteroides-dominant composition to one with higher diversity, either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network, or a moderate/high-diversity composition with abundant but not excessive levels of Prevotella copri.<br><br>CONCLUSIONS: This systematic review/meta-analysis yielded a coherent picture from a compositional perspective, which may help identify beneficial donor profiles and guide personalized FMT approaches.}, }
@article {pmid39442742, year = {2025}, author = {Claytor, JD and Faith, JJ}, title = {Fecal Microbiota Transplantation (FMT) in Ulcerative Colitis: Holding Out for a Superdonor?.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {23}, number = {4}, pages = {516-518}, doi = {10.1016/j.cgh.2024.07.047}, pmid = {39442742}, issn = {1542-7714}, }
@article {pmid39442279, year = {2024}, author = {Yang, X and Xin, Y and Gu, Y and Wang, Y and Hu, X and Ying, G and Zhang, Q and He, X}, title = {Total alkaloids of Aconitum carmichaelii Debx alleviate cisplatin-induced acute renal injury by inhibiting inflammation and oxidative stress related to gut microbiota metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156128}, doi = {10.1016/j.phymed.2024.156128}, pmid = {39442279}, issn = {1618-095X}, mesh = {*Acute Kidney Injury/chemically induced/drug therapy ; *Gastrointestinal Microbiome/drug effects ; *Cisplatin/adverse effects ; *Oxidative Stress/drug effects ; *Aconitum/chemistry ; *Alkaloids/pharmacology ; Animals ; Male ; Mice ; Anti-Inflammatory Agents/pharmacology ; Inflammation/drug therapy ; Fecal Microbiota Transplantation ; Kidney/drug effects ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Cisplatin-induced acute kidney injury (AKI) is a complex and serious clinical issue, representing a major cause of hospital-acquired AKI. Alkaloids are the main active constituents of Aconitum carmichaelii Debx, which exhibit protective effects in several kidney disease models and against other acute organ injuries. However, its activity and mechanism of action in AKI treatment remain unclear.<br><br>PURPOSE: This study aimed to elucidate the effect of Aconitum carmichaelii Debx (ACA) in a model of cisplain-induced AKI and comprehensively investigate its underlying mechanisms.<br><br>METHODS: The major alkaloids in ACA were analyzed using high-performance liquid chromatography. Blood urea nitrogen (BUN) and serum creatine levels were measured using automated biochemical instruments. 16S rRNA sequencing, short-chain fatty acid (SCFA) analysis, fecal microbiota transplantation (FMT), non-targeted metabolomics, and transcriptomics were performed to systematically identify prospective biomarkers after ACA treatment. Anti-inflammatory and anti-oxidative stress activities were monitored using ELISA and western blotting.<br><br>RESULTS: Four main compounds (fuziline, neoline, talatisamine, and songorine) were identified in ACA. ACA significantly alleviated cisplatin-induced AKI by reducing (BUN) and serum creatine levels and improving histopathological scores. Moreover, ACA balanced cisplatin-mediated confoundments in microbial composition and function, including decreasing the levels of Escherichia-Shigella, Clostridium, and Ruminococcus, as well as increasing Ligilactobacillus, Anaerotruncus, Bacteroides and Desulfovibrio levels, accompanied by uremic toxin reduction, and augmenting serum SCFAs. The FMT experiments further confirmed that ACA exerts anti-AKI effects by affecting gut microbiota. A multi-omics study has shown that ACA regulates glutathione and tryptophan metabolism and mediates pathways that trigger inflammatory responses. Finally, ACA reduced serum levels of inflammatory factors (IL-1&#x3b2;, IL-6, and TNF-&#x3b1;), restored enzymes of the antioxidative system (SOD and CAT) and GSH values, and decreased monoester diterpene alkaloid levels in the kidney by inhibiting the expression of NF-&#x3ba;B pathway-related proteins and increasing Nrf2/HO-1 pathway-related protein expression.<br><br>CONCLUSION: ACA protects against cisplatin-induced AKI through its anti-inflammatory and antioxidant functions, which may be associated with the restoration of gut microbiota metabolism. ACA is a potential drug for AKI and other forms of organ damage related to the disruption of the gut microbiota.}, }
@article {pmid39439945, year = {2024}, author = {Chen, W and Zou, H and Xu, H and Cao, R and Zhang, H and Zhang, Y and Zhao, J}, title = {The potential influence and intervention measures of gut microbiota on sperm: it is time to focus on testis-gut microbiota axis.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1478082}, pmid = {39439945}, issn = {1664-302X}, abstract = {As the global male infertility rate continues to rise, there is an urgent imperative to investigate the underlying causes of sustained deterioration in sperm quality. The gut microbiota emerges as a pivotal factor in host health regulation, with mounting evidence highlighting its dual influence on semen. This review underscores the interplay between the Testis-Gut microbiota axis and its consequential effects on sperm. Potential mechanisms driving the dual impact of gut microbiota on sperm encompass immune modulation, inflammatory responses mediated by endotoxins, oxidative stress, antioxidant defenses, gut microbiota-derived metabolites, epigenetic modifications, regulatory sex hormone signaling. Interventions such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and Traditional natural herbal extracts are hypothesized to rectify dysbiosis, offering avenues to modulate gut microbiota and enhance Spermatogenesis and motility. Future investigations should delve into elucidating the mechanisms and foundational principles governing the interaction between gut microbiota and sperm within the Testis-Gut microbiota Axis. Understanding and modulating the Testis-Gut microbiota Axis may yield novel therapeutic strategies to enhance male fertility and combat the global decline in sperm quality.}, }
@article {pmid39438902, year = {2024}, author = {Díaz-García, C and Moreno, E and Talavera-Rodríguez, A and Martín-Fernández, L and González-Bodí, S and Martín-Pedraza, L and Pérez-Molina, JA and Dronda, F and Gosalbes, MJ and Luna, L and Vivancos, MJ and Huerta-Cepas, J and Moreno, S and Serrano-Villar, S}, title = {Fecal microbiota transplantation alters the proteomic landscape of inflammation in HIV: identifying bacterial drivers.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {214}, pmid = {39438902}, issn = {2049-2618}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *HIV Infections/therapy ; *Gastrointestinal Microbiome ; *Inflammation ; Male ; Middle Aged ; Female ; *Proteomics/methods ; Adult ; *Feces/microbiology ; Pilot Projects ; Double-Blind Method ; Bacteria/classification/isolation &amp; purification/metabolism ; }, abstract = {BACKGROUND: Despite effective antiretroviral therapy, people with HIV (PWH) experience persistent systemic inflammation and increased morbidity and mortality. Modulating the gut microbiome through fecal microbiota transplantation (FMT) represents a novel therapeutic strategy. We aimed to evaluate proteomic changes in inflammatory pathways following repeated, low-dose FMT versus placebo.<br><br>METHODS: This double-masked, placebo-controlled pilot study assessed the proteomic impacts of weekly FMT versus placebo treatment over 8&#xa0;weeks on systemic inflammation in 29 PWH receiving stable antiretroviral therapy (ART). Three stool donors with high Faecalibacterium and butyrate profiles were selected, and their individual stools were used for FMT capsule preparation. Proteomic changes in 345 inflammatory proteins in plasma were quantified using the proximity extension assay, with samples collected at baseline and at weeks 1, 8, and 24. Concurrently, we characterized shifts in the gut microbiota composition and annotated functions through shotgun metagenomics. We fitted generalized additive models to evaluate the dynamics of protein expression. We selected the most relevant proteins to explore their correlations with microbiome composition and functionality over time using linear mixed models.<br><br>RESULTS: FMT significantly reduced the plasma levels of 45 inflammatory proteins, including established mortality predictors such as IL6 and TNF-&#x3b1;. We found notable reductions persisting up to 16&#xa0;weeks after the final FMT procedure, including in the expression of proteins such as CCL20 and CD22. We identified changes in 46 proteins, including decreases in FT3LG, IL6, IL10RB, IL12B, and IL17A, which correlated with multiple bacterial species. We found that specific bacterial species within the Ruminococcaceae, Succinivibrionaceae, Prevotellaceae families, and the Clostridium genus, in addition to their associated genes and functions, were significantly correlated with changes in inflammatory markers.<br><br>CONCLUSIONS: Targeting the gut microbiome through FMT effectively decreased inflammatory proteins in PWH, with sustained effects. These findings suggest the potential of the microbiome as a therapeutic target to mitigate inflammation-related complications in this population, encouraging further research and development of microbiome-based interventions. Video Abstract.}, }
@article {pmid39437686, year = {2024}, author = {Cao, Z and Wang, X and Liu, H and Yang, Z and Zeng, Z}, title = {Gut microbiota mediate the alleviation effect of Xiehuo-Guzheng granules on β cell dedifferentiation in type 2 diabetes mellitus.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156151}, doi = {10.1016/j.phymed.2024.156151}, pmid = {39437686}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diabetes Mellitus, Type 2/drug therapy/therapy ; Male ; *Insulin-Secreting Cells/drug effects ; *Diabetes Mellitus, Experimental/drug therapy ; *Drugs, Chinese Herbal/pharmacology ; *Rats, Sprague-Dawley ; Rats ; Cell Dedifferentiation/drug effects ; Fecal Microbiota Transplantation ; Fatty Acids, Volatile/metabolism ; Metformin/pharmacology ; Diet, High-Fat ; Cytokines/metabolism ; Hypoglycemic Agents/pharmacology ; Blood Glucose ; }, abstract = {BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide public health problem characterized by a progressive decline in β cell function. In traditional Chinese medicine (TCM) theory, 'fire' and 'healthy qi deficiency' are important pathogeneses of T2DM, and purging 'fire' and reinforcing the 'healthy qi' (Pinyin name: Xiehuo-Guzheng, XHGZ) are important method of treatment. Over the years, we have observed its benefit for diabetes. However, the underlying mechanisms remain unclear.<br><br>PURPOSE: To investigate the mechanism of XHGZ granules against &#x3b2; cell dedifferentiation in T2DM based on gut microbiota.<br><br>METHODS: Rats with T2DM, induced by intraperitoneal injection of streptozotocin after eight weeks of high-fat diet, were randomly allocated to receive XHGZ granules, metformin, or distilled water for eight consecutive weeks. Changes in metabolic parameters, &#x3b2; cell dedifferentiation, inflammatory cytokines, gut microbiota, and microbial metabolites (lipopolysaccharide (LPS) and short-chain fatty acids (SCFAs)), were detected. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the anti-diabetic effect of XHGZ granule-regulated gut microbiota in pseudo-germ-free T2DM rats.<br><br>RESULTS: XHGZ granules significantly ameliorated hyperglycaemia, improved islet function and pathology, and reduced &#x3b2; cell dedifferentiation and pro-inflammatory cytokines in T2DM rats. 16S rRNA sequencing revealed that XHGZ granules decreased the LPS-containing microbiota (e.g., Colidextribacter, Desulfovibrionaceae, and Morganella) and increased the SCFAs-producing bacteria (e.g., Prevotella, Alloprevotella, and Muribaculaceae) and Lactobacillus_intestinalis. Correspondingly, it strengthened intestinal barrier, lowered LPS, and elevated acetic and butyric acids. Tax4Fun analysis indicated that XHGZ granules restored abnormal metabolism, lipopolysaccharide biosynthesis, and pantothenate and CoA biosynthesis. Moreover, the XHGZ granule-regulated microbiota also exhibited the effects of anti-diabetes, anti-&#x3b2; cell dedifferentiation, and anti-inflammation along with the reduction of LPS and the increase of SCFAs in pseudo-germ-free T2DM rats.<br><br>CONCLUSION: Our results show that XHGZ granules alleviate &#x3b2; cell dedifferentiation via regulating gut microbiota and their metabolites in T2DM, suggesting its potential as a promising complementary treatment for T2DM. As far as we know, there are very few studies on the alleviation of &#x3b2; cell dedifferentiation by TCM, and investigations into the mechanism from the perspective of intestinal flora and microbial metabolites are yet to be reported.}, }
@article {pmid39437444, year = {2024}, author = {Ciernikova, S and Sevcikova, A and Mego, M}, title = {Targeting the gut and tumor microbiome in cancer treatment resistance.}, journal = {American journal of physiology. Cell physiology}, volume = {327}, number = {6}, pages = {C1433-C1450}, doi = {10.1152/ajpcell.00201.2024}, pmid = {39437444}, issn = {1522-1563}, support = {2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; 1/0071/24//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, mesh = {Animals ; Humans ; Antineoplastic Agents/pharmacology/therapeutic use ; *Drug Resistance, Neoplasm ; Dysbiosis/microbiology/physiopathology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/physiology ; *Neoplasms/drug therapy/immunology/microbiology/pathology ; Probiotics/administration &amp; dosage ; *Tumor Microenvironment ; }, abstract = {Therapy resistance represents a significant challenge in oncology, occurring in various therapeutic approaches. Recently, animal models and an increasing set of clinical trials highlight the crucial impact of the gut and tumor microbiome on treatment response. The intestinal microbiome contributes to cancer initiation, progression, and formation of distant metastasis. In addition, tumor-associated microbiota is considered a critical player in influencing tumor microenvironments and regulating local immune processes. Intriguingly, numerous studies have successfully identified pathogens within the gut and tumor microbiome that might be linked to a poor response to different therapeutic modalities. The unfavorable microbial composition with the presence of specific microbes participates in cancer resistance and progression via several mechanisms, including upregulation of oncogenic pathways, macrophage polarization reprogramming, metabolism of chemotherapeutic compounds, autophagy pathway modulation, enhanced DNA damage repair, inactivation of a proapoptotic cascade, and bacterial secretion of extracellular vesicles, promoting the processes in the metastatic cascade. Targeted elimination of specific intratumoral bacteria appears to enhance treatment response. However, broad-spectrum antibiotic pretreatment is mostly connected to reduced efficacy due to gut dysbiosis and lower diversity. Mounting evidence supports the potential of microbiota modulation by probiotics and fecal microbiota transplantation to improve intestinal dysbiosis and increase microbial diversity, leading to enhanced treatment efficacy while mitigating adverse effects. In this context, further research concerning the identification of clinically relevant microbiome signatures followed by microbiota-targeted strategies presents a promising approach to overcoming immunotherapy and chemotherapy resistance in refractory patients, improving their outcomes.}, }
@article {pmid39435211, year = {2024}, author = {Koneru, HM and Sarwar, H and Bandi, VV and Sinha, M and Tarar, P and Bishara, R and Malasevskaia, I}, title = {A Systematic Review of Gut Microbiota Diversity: A Key Player in the Management and Prevention of Diabetes Mellitus.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69687}, pmid = {39435211}, issn = {2168-8184}, abstract = {Diabetes mellitus represents a significant global health challenge, characterized by impaired insulin production and action, leading to elevated blood glucose levels. This systematic review investigates the association between gut microbiota composition and diversity, along with the structural and functional characteristics of the gut microbiome, and their implications for the risk, prevention, and management of both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a comprehensive search across multiple databases yielded 16 studies that met the inclusion criteria. The findings highlight the potential of gut microbiota interventions, such as fecal microbiota transplantation and probiotic supplementation, in improving metabolic parameters and glycemic control. Notably, the review underscores the importance of dietary interventions and the role of specific microbial populations in influencing diabetes outcomes. Despite the promising results, the variability in study designs, sample sizes, and methodologies poses challenges for generalizability and interpretation. This review emphasizes the need for further research to elucidate the mechanisms underlying these associations and to explore personalized microbiome-based therapies in diabetes management. The insights gained could pave the way for innovative therapeutic strategies aimed at harnessing gut health to mitigate the burden of diabetes mellitus.}, }
@article {pmid39434180, year = {2024}, author = {Yan, S and Du, R and Yao, W and Zhang, H and Xue, Y and Teligun,  and Li, Y and Bao, H and Zhao, Y and Cao, S and Cao, G and Li, X and Bao, S and Song, Y}, title = {Host-microbe interaction-mediated resistance to DSS-induced inflammatory enteritis in sheep.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {208}, pmid = {39434180}, issn = {2049-2618}, mesh = {Animals ; Sheep/microbiology ; Mice ; *Dextran Sulfate ; *Gastrointestinal Microbiome ; *Disease Models, Animal ; *Feces/microbiology ; *Colitis/microbiology/chemically induced ; Host Microbial Interactions ; Fecal Microbiota Transplantation ; Disease Resistance ; Enteritis/microbiology/veterinary ; Sheep Diseases/microbiology ; Bacteria/classification/isolation &amp; purification/genetics ; }, abstract = {BACKGROUND: The disease resistance phenotype is closely related to immunomodulatory function and immune tolerance and has far-reaching implications in animal husbandry and human health. Microbes play an important role in the initiation, prevention, and treatment of diseases, but the mechanisms of host-microbiota interactions in disease-resistant phenotypes are poorly understood. In this study, we hope to uncover and explain the role of microbes in intestinal diseases and their mechanisms of action to identify new potential treatments.<br><br>METHODS: First, we established the colitis model of DSS in two breeds of sheep and then collected the samples for multi-omics testing including metagenes, metabolome, and transcriptome. Next, we made the fecal bacteria liquid from the four groups of sheep feces collected from H-CON, H-DSS, E-CON, and E-DSS to transplant the fecal bacteria into mice. H-CON feces were transplanted into mice named HH group and H-DSS feces were transplanted into mice named HD group and Roseburia bacteria treatment named HDR groups. E-CON feces were transplanted into mice named EH group and E-DSS feces were transplanted into mice in the ED group and Roseburia bacteria treatment named EDR groups. After successful modeling, samples were taken for multi-omics testing. Finally, colitis mice in HD group and ED group were administrated with Roseburia bacteria, and the treatment effect was evaluated by H&amp;E, PAS, immunohistochemistry, and other experimental methods.<br><br>RESULTS: The difference in disease resistance of sheep to DSS-induced colitis disease is mainly due to the increase in the abundance of Roseburia bacteria and the increase of bile acid secretion in the intestinal tract of Hu sheep in addition to the accumulation of potentially harmful bacteria in the intestine when the disease occurs, which makes the disease resistance of Hu sheep stronger under the same disease conditions. However, the enrichment of harmful microorganisms in East Friesian sheep activated the TNF&#x3b1; signalling pathway, which aggravated the intestinal injury, and then the treatment of FMT mice by culturing Roseburia bacteria found that Roseburia bacteria had a good curative effect on colitis.<br><br>CONCLUSION: Our study showed that in H-DSS-treated sheep, the intestinal barrier is stabilized with an increase in the abundance of beneficial microorganisms. Our data also suggest that Roseburia bacteria have a protective effect on the intestinal barrier of Hu sheep. Accumulating evidence suggests that host-microbiota interactions are associated with IBD disease progression. Video Abstract.}, }
@article {pmid39432486, year = {2024}, author = {Ebrahimi, R and Masouri, MM and Salehi Amniyeh Khozani, AA and Ramadhan Hussein, D and Nejadghaderi, SA}, title = {Safety and efficacy of fecal microbiota transplantation for viral diseases: A systematic review of clinical trials.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0311731}, pmid = {39432486}, issn = {1932-6203}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Virus Diseases/therapy ; COVID-19/therapy ; Gastrointestinal Microbiome ; Hepatitis B/therapy ; HIV Infections/therapy/microbiology ; Clinical Trials as Topic ; Treatment Outcome ; Clostridium Infections/therapy/microbiology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Gut microbiota play important roles in several diseases like viral infections. In this systematic review, our objective was to assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating various viral diseases.<br><br>METHODS: We conducted searches on databases including PubMed, Web of Science, Scopus, and Google Scholar until November 2023. Clinical trials reported outcomes related to safety of FMT or its efficacy in patients with viral diseases were included. We excluded other types of studies that enrolled healthy individuals or patients with other disorders and did not use FMT. The assessment of bias risk was conducted using the National Institutes of Health (NIH) study quality evaluation tool.<br><br>RESULTS: Eight studies with total 196 participants were included. Viral diseases were human immunodeficiency virus (HIV), hepatitis B, COVID-19 and Clostridioides difficile coinfection, and cytomegalovirus colitis. In hepatitis B cases, HBeAg clearance was significant in those received FMT (p<0.01), while it was not significant in another one (p = 0.19). A clinical response was noted in 37.5% of patients with cytomegalovirus colitis, with an equal percentage achieving clinical remission post-FMT. There was a significant reduction in Clostridioides difficile relapse rate in FMT group than controls in coinfection of Clostridioides difficile and COVID-19 (2.17% vs. 42.5%, p<0.05). In patients with HIV, partial engraftment of the donor microbiome and increases in alpha diversity were observed after FMT. No severe adverse events were reported. Most studies had fair or good qualities.<br><br>CONCLUSIONS: Our findings revealed FMT as a promising, safe treatment for some viral diseases. It improved viral clearance, clinical outcomes, and inflammation. However, the varying responses and small sample sizes call for more trials on FMT in viral diseases.}, }
@article {pmid39431286, year = {2024}, author = {Liu, T and Zhou, L and Dong, R and Qu, Y and Liu, Y and Song, W and Lv, J and Wu, S and Peng, W and Shi, L}, title = {Isomalto-Oligosaccharide Potentiates Alleviating Effects of Intermittent Fasting on Obesity-Related Cognitive Impairment during Weight Loss and the Rebound Weight Gain.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {43}, pages = {23875-23892}, doi = {10.1021/acs.jafc.4c07351}, pmid = {39431286}, issn = {1520-5118}, mesh = {Animals ; *Cognitive Dysfunction/etiology/metabolism ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Obesity/metabolism ; Male ; *Mice, Inbred C57BL ; *Toll-Like Receptor 4/metabolism/genetics ; *Oligosaccharides/administration &amp; dosage ; *Fasting ; Humans ; *Weight Gain/drug effects ; Weight Loss/drug effects ; NF-kappa B/metabolism/genetics ; Hippocampus/metabolism/drug effects ; Diet, High-Fat/adverse effects ; Bacteria/classification/genetics/isolation &amp; purification/metabolism/drug effects ; Intermittent Fasting ; }, abstract = {Obesity-related cognitive dysfunction poses a significant threat to public health. The present study demonstrated mitigating effects of intermittent fasting (IF) and its combination with isomalto-oligosaccharides and IF (IF + IMO) on cognitive impairments induced by a high-fat-high-fructose (HFHF) diet in mice, with IF + IMO exhibiting superior effects. Transcriptomic analysis of the hippocampus revealed that the protective effects on cognition might be attributed to the suppression of toll-like receptor 4 (TLR4)/NFκB signaling, oxidative phosphorylation, and neuroinflammation. Moreover, both IF and IF + IMO modulated the gut microbiome and promoted the production of short-chain fatty acids, with IF + IMO displaying more pronounced effects. IF + IMO-modulated gut microbiota, metabolites, and molecular targets associated with cognitive impairments were further corroborated using human data from public databases Gmrepo and gutMgene. Furthermore, the fecal microbiome transplantation confirmed the direct impacts of IF + IMO-derived microbiota on improving cognition functions by suppressing TLR4/NFκB signaling and increasing BDNF levels. Notably, prior exposure to IF + IMO prevented weight-regain-induced cognitive decline, suppressed TLR4/NFκB signaling and inflammatory cytokines in the hippocampus, and mitigated weight regain-caused gut dysbacteriosis without altering body weight. Our study underscores that IMO-augmented alleviating effects of IF on obesity-related cognitive impairment particularly during weight-loss and weight-regain periods, presenting a novel nutritional strategy to tackle obesity-related neurodegenerative disorders.}, }
@article {pmid39427741, year = {2025}, author = {Sun, Z and Zeng, Z and Chen, LX and Xu, JD and Zhou, J and Kong, M and Shen, H and Mao, Q and Wu, CY and Long, F and Zhou, SS and Li, SL}, title = {Integrated anti-fatigue effects of polysaccharides and small molecules coexisting in water extracts of ginseng: Gut microbiota-mediated mechanisms.}, journal = {Journal of ethnopharmacology}, volume = {337}, number = {Pt 3}, pages = {118958}, doi = {10.1016/j.jep.2024.118958}, pmid = {39427741}, issn = {1872-7573}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Panax/chemistry ; Animals ; *Polysaccharides/pharmacology ; *Fatigue/drug therapy ; Male ; *Plant Extracts/pharmacology ; *Rats, Sprague-Dawley ; Rats ; *Oxidative Stress/drug effects ; Ginsenosides/pharmacology ; Energy Metabolism/drug effects ; Water/chemistry ; Fecal Microbiota Transplantation ; }, abstract = {Both clinical and animal studies have demonstrated that ginseng has curative effects on fatigue. Our previous study found that water extracts of ginseng (WEG) could significantly mitigate exercise-induced fatigue (EF). Notably, polysaccharides (GP) and small molecules (GS, mainly ginsenosides) coexist in WEG. Whether and how GP and GS contribute to the anti-EF effects of WEG remains unknown.<br><br>AIM OF THE STUDY: To evaluate the contribution of GP and GS to the anti-EF effects of WEG and clarify the potential gut microbiota-mediated mechanisms.<br><br>MATERIALS AND METHODS: Firstly, the anti-EF effects of WEG, GP and GS were comparatively investigated by determining fatigue phenotypes (energy metabolism and oxidative stress parameters), gut microbiota composition as well as exogenous and endogenous metabolites in EF modeling rats. Then, the gut microbiota mediated mechanisms were verified by antibiotics (ABX) intervention and fecal microbial transplantation (FMT).<br><br>RESULTS: GP, GS and WEG each exhibited distinct anti-EF effects in differentially improving EF-induced energy metabolism abnormality and oxidative stress, reshaping gut microbiota composition, and elevating systemic metabolites. Notably, WEG showed stronger anti-EF effects than both GP and GS, characterized by better alleviation of disturbances in energy metabolism (e.g. Glc) and oxidative stress parameters (e.g. SOD), regulation of gut microbiota homeostasis (e.g. enriching the genus Coprococcus and species Collinsella provencensis etc.), as well as increases in exogenous secondary ginsenosides (e.g. 20(S)-Rg3, 20(R)-Rg3, CK), endogenous bile acids (BAs) (e.g. CA, DCA, LCA), and short chain fatty acids (SCFAs) (e.g. butyric acid). The stronger anti-EF effects of WEG compared to GP and GS could be abolished by ABX intervention, and transferred by FMT.<br><br>CONCLUSION: GP and GS could collectively contribute to the anti-EF effects of WEG through integrated actions. Gut microbiota mediate the integrated anti-EF effects of GP and GS in WEG, potentially by regulating the levels of exogenous bioactive secondary ginsenosides, as well as endogenous BAs and SCFAs, thereby alleviating fatigue-related energy metabolic abnormalities and oxidative stress.}, }
@article {pmid39426981, year = {2024}, author = {Lu, C and Liu, D and Wu, Q and Zeng, J and Xiong, Y and Luo, T}, title = {EphA2 blockage ALW-II-41-27 alleviates atherosclerosis by remodeling gut microbiota to regulate bile acid metabolism.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {108}, pmid = {39426981}, issn = {2055-5008}, support = {2023NSFSC1631//Department of Science and Technology of Sichuan Province (Sichuan Provincial Department of Science and Technology)/ ; 2023YFS0116//Department of Science and Technology of Sichuan Province (Sichuan Provincial Department of Science and Technology)/ ; 2022YFS0604//Department of Science and Technology of Sichuan Province (Sichuan Provincial Department of Science and Technology)/ ; Q22066//Education Department of Sichuan Province/ ; }, mesh = {Animals ; *Atherosclerosis/metabolism/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Bile Acids and Salts/metabolism ; Mice ; *Receptor, EphA2/metabolism ; *Diet, High-Fat/adverse effects ; Male ; Humans ; Disease Models, Animal ; Plaque, Atherosclerotic/etiology ; Mice, Inbred C57BL ; Bacteria/classification/isolation &amp; purification/genetics/metabolism ; Dysbiosis ; }, abstract = {Coronary artery disease (CAD), a critical condition resulting from systemic inflammation, metabolic dysfunction, and gut microbiota dysbiosis, poses a global public health challenge. ALW-II-41-27, a specific inhibitor of the EphA2 receptor, has shown anti-inflammatory prosperities. However, the impact of ALW-II-41-27 on atherosclerosis has not been elucidated. This study aimed to examine the roles of pharmacologically inhibiting EphA2 and the underlying mechanism in ameliorating atherosclerosis. ALW-II-41-27 was administered to apoE[-/-] mice fed a high-fat diet via intraperitoneal injection. We first discovered that ALW-II-41-27 led to a significant reduction in atherosclerotic plaques, evidenced by reduced lipid and macrophage accumulation, alongside an increase in collagen and smooth muscle cell content. ALW-II-41-27 also significantly lowered plasma and hepatic cholesterol levels, as well as the colonic inflammation. Furthermore, gut microbiota was analyzed by metagenomics and plasma metabolites by untargeted metabolomics. ALW-II-41-27-treated mice enriched Enterococcus, Akkermansia, Eggerthella and Lactobaccilus, accompanied by enhanced secondary bile acids production. To explore the causal link between ALW-II-41-27-associated gut microbiota and atherosclerosis, fecal microbiota transplantation was employed. Mice that received ALW-II-41-27-treated mouse feces exhibited the attenuated atherosclerotic plaque. In clinical, lower plasma DCA and HDCA levels were determined in CAD patients using quantitative metabolomics and exhibited a negative correlation with higher monocytes EphA2 expression. Our findings underscore the potential of ALW-II-41-27 as a novel therapeutic agent for atherosclerosis, highlighting its capacity to modulate gut microbiota composition and bile acid metabolism, thereby offering a promising avenue for CAD.}, }
@article {pmid39426255, year = {2024}, author = {Liu, SJ and Fu, JJ and Liao, ZY and Liu, YX and He, J and He, LY and Bai, J and Yang, JY and Niu, SQ and Guo, JL}, title = {Z-ligustilide alleviates atherosclerosis by reconstructing gut microbiota and sustaining gut barrier integrity through activation of cannabinoid receptor 2.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156117}, doi = {10.1016/j.phymed.2024.156117}, pmid = {39426255}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Atherosclerosis/drug therapy ; Caco-2 Cells ; Mice ; Male ; *Receptor, Cannabinoid, CB2/metabolism ; *4-Butyrolactone/analogs &amp; derivatives/pharmacology ; Disease Models, Animal ; Ligusticum ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Intestinal Mucosa/drug effects/metabolism ; }, abstract = {BACKGROUND: Z-Ligustilide (ZL) is an essential phthalide found in Ligusticum chuanxiong Hort, a commonly used traditional Chinese medicine for treating atherosclerosis (AS) clinically. ZL has been shown to be effective in treating AS. However, the underlying mechanism of ZL against AS and its potential targets remain elusive.<br><br>PURPOSE: The purpose of this research was to assess the influence of ZL on AS and explore the role of the gut microbiome in mediating this effect.<br><br>METHODS: A well-established AS mouse model, apolipoprotein E deficient (ApoE[-/-]) mice was used to examine the effects of ZL on AS, inflammation, and the intestinal barrier. To analyze the changes in gut microbial community, we employed the 16S rRNA gene sequencing. Antibiotic cocktail and fecal microbiota transplantation (FMT) were employed to clarify the contribution of the gut microbiota to the anti-AS effects of ZL. The mechanism through which ZL provided protective effects on AS and the intestinal barrier was explored by untargeted metabolomics, as well as by validating the involvement of cannabinoid receptor 2 (CB2R) in mice and Caco-2 cells.<br><br>RESULTS: Oral administration of ZL inhibited the development of atherosclerotic lesions, improved plaque stability, inhibited the increase in serum and atherosclerotic inflammation, and improved intestinal barrier function. Fecal bacteria from ZL-treated mice induced similar beneficial effects on AS and the intestinal barrier. We used 16S RNA gene sequencing to reveal a significant increase in Rikenella abundance in both ZL-treated mice and ZL-FMT mice, which was associated with the beneficial effects of ZL. Further function prediction analysis of the gut microbiota and CB2R antagonist intervention experiment in mice and Caco-2 cells showed that the activation of CB2R resulted in the enhancement of the intestinal barrier by ZL. Furthermore, the analysis of metabolomic profiling revealed the enrichment of capsaicin upon ZL treatment, which induced the activation of CB2R in human colon epithelial cells.<br><br>CONCLUSION: Our study is the first to demonstrate that oral treatment with ZL has the potential to alleviate AS by reducing inflammation levels and enhancing the intestinal barrier function. This mechanism relies on the gut microbiota in a CB2R-dependent manner, suggesting promising strategies and ideas for managing AS. This study provides insights into a novel mechanism for treating AS with ZL.}, }
@article {pmid39425119, year = {2024}, author = {Qian, X and Lin, X and Hu, W and Zhang, L and Chen, W and Zhang, S and Ge, S and Xu, X and Luo, K}, title = {Intestinal homeostasis disrupted by Periodontitis exacerbates Alzheimer's Disease in APP/PS1 mice.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {263}, pmid = {39425119}, issn = {1742-2094}, support = {81860197//the National Natural Science Foundation of China/ ; 2020Y9032//the Joint Funds for the Innovation of Science and Technology/ ; JAT220078//the Educational Research Project for Young and Middle-aged Teachers of Fujian Provincial Department of Education/ ; 82301103//National Outstanding Youth Science Fund Project of National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Alzheimer Disease/pathology/metabolism ; Mice ; *Homeostasis/physiology ; *Mice, Transgenic ; *Periodontitis/pathology/complications/microbiology ; *Amyloid beta-Protein Precursor/genetics/metabolism ; *Gastrointestinal Microbiome/physiology ; *Presenilin-1/genetics ; Intestines/pathology ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {Periodontitis exacerbates Alzheimer's disease (AD) through multiple pathways. Both periodontitis and AD are intricately correlated to intestinal homeostasis, yet there is still a lack of direct evidence regarding whether periodontitis can regulate the progression of AD by modulating intestinal homeostasis. The current study induced experimental periodontitis in AD mice by bilaterally ligating the maxillary second molars with silk and administering Pg-LPS injections in APP[swe]/PS1[ΔE9] (APP/PS1) mice. Behavioral tests and histological analyses of brain tissue were conducted after 8 weeks. Gut microbiota was analyzed and colon tissue were also evaluated. Then, fecal microbiota from mice with periodontitis was transplanted into antibiotic-treated mice to confirm the effects of periodontitis on AD and the potential mechanism was explored. The results indicated periodontitis exacerbated cognitive impairment and anxious behaviour in APP/PS1 mice, with increased Aβ deposition, microglial overactivation and neuroinflammation in brain. Moreover, the intestinal homeostasis of AD mice was altered by periodontitis, including affecting gut microbiota composition, causing colon inflammation and destroyed intestinal epithelial barrier. Furthermore, AD mice that underwent fecal transplantation from mice with periodontitis exhibited worsened AD progression and disrupted intestinal homeostasis. It also impaired intestinal barrier function, elevated peripheral inflammation, damaged blood-brain barrier (BBB) and caused neuroinflammation and synapses impairment. Taken together, the current study demonstrated that periodontitis could disrupt intestinal homeostasis to exacerbate AD progression potential via causing gut microbial dysbiosis, intestinal inflammation and intestinal barrier impairment to induce peripheral inflammation and damage BBB, ultimately leading to neuroinflammation and synapse impairment. It underscores the importance of maintaining both periodontal health and intestinal homeostasis to reduce the risk of AD.}, }
@article {pmid39423571, year = {2024}, author = {Li, Y and Yan, M and Zhang, M and Zhang, B and Xu, B and Ding, X and Wang, J and Wang, Z}, title = {Scutellarin alleviated ulcerative colitis through gut microbiota-mediated cAMP/PKA/NF-κB pathway.}, journal = {Biochemical and biophysical research communications}, volume = {735}, number = {}, pages = {150837}, doi = {10.1016/j.bbrc.2024.150837}, pmid = {39423571}, issn = {1090-2104}, mesh = {Animals ; *Glucuronates/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; *Apigenin/pharmacology/therapeutic use ; *Colitis, Ulcerative/drug therapy/metabolism/microbiology ; *NF-kappa B/metabolism ; Mice ; *Mice, Inbred C57BL ; Male ; *Dextran Sulfate ; *Signal Transduction/drug effects ; *Cyclic AMP-Dependent Protein Kinases/metabolism ; *Cyclic AMP/metabolism ; Fecal Microbiota Transplantation ; Colon/metabolism/drug effects/pathology/microbiology ; }, abstract = {PURPOSE: Ulcerative colitis (UC) is a chronic, non-specific inflammatory condition of the colon, characterized by recurrent episodes and a notable lack of effective pharmacological treatments. Scutellarin, a natural component, exhibits appreciable pharmacological effects and therapeutic potential for various diseases. However, its effects on UC are not fully understood, and the precise mechanisms remain to be deciphered. This study aimed to assess the therapeutic efficacy of scutellarin and elucidate its underlying mechanisms in treating UC.<br><br>METHODS: This study utilized dextran sulfate sodium (DSS)-induced mice to evaluate the therapeutic potential of scutellarin against UC and to elucidate the mechanisms involving the gut microbiota. An antibiotics cocktail (ABX) and fecal microbiota transplantation (FMT) were also used to determine the mechanistic role of the gut microbiota. An integrative approach combining fecal metabolomics and network pharmacology analysis was used to explore the gut microbiota-directed molecular mechanism.<br><br>RESULTS: The results showed that scutellarin provided various therapeutic benefits in UC management, including alleviating weight loss, slowing disease progression, and reducing inflammatory damage in colon structures. The improved gut microbiota after scutellarin administration contributed to these effects. Fecal metabolome revealed that scutellarin selectively mitigated DSS-induced dysregulation of gut microbiota-derived metabolites, including glycolic acid, &#x3b3;-aminobutyric acid, glutamate, tryptophan, xanthine, and &#x3b2;-hydroxypyruvate. Network pharmacology analysis, along with in vivo experimental verification, implicated the cAMP/PKA/NF-&#x3ba;B pathway in the action of these metabolites in treating UC, which may be the mechanism responsible for scutellarin's curative effects on UC.<br><br>CONCLUSION: This study demonstrates the potential of scutellarin in alleviating UC by activating the cAMP/PKA/NF-&#x3ba;B pathway through gut microbiota-derived metabolites, highlighting scutellarin as a promising therapeutic agent for UC.}, }
@article {pmid39423480, year = {2024}, author = {Xiao, Q and Luo, L and Zhu, X and Yan, Y and Li, S and Chen, L and Wang, X and Zhang, J and Liu, D and Liu, R and Zhong, Y}, title = {Formononetin alleviates ulcerative colitis via reshaping the balance of M1/M2 macrophage polarization in a gut microbiota-dependent manner.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156153}, doi = {10.1016/j.phymed.2024.156153}, pmid = {39423480}, issn = {1618-095X}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/chemically induced ; *Gastrointestinal Microbiome/drug effects ; *Macrophages/drug effects ; *Isoflavones/pharmacology ; Mice ; *Dextran Sulfate ; Male ; *Colon/drug effects/microbiology ; Mice, Inbred C57BL ; Disease Models, Animal ; Cytokines/metabolism ; Anti-Inflammatory Agents/pharmacology ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Ulcerative colitis (UC), a type of inflammatory bowel disease, presents substantial challenges in clinical treatment due to the limitations of current medications. Formononetin (FN), a naturally compound with widespread availability, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties.<br><br>PURPOSE: This study aimed to investigate the efficacy of FN against UC and its potential regulatory mechanism.<br><br>METHODS: Here, dextran sulfate sodium (DSS) was employed to replicate experimental colitis in mice with concomitant FN treatment. The distribution and localisation of CD68 and F4/80 macrophages in colonic tissues were visualized by immunofluorescence, their chemokine and inflammatory cytokine concentrations were determined by ELISA, and macrophages and M1/M2 subpopulations were determined by flow cytometry. Additionally, 16 s rRNA and LC-MS techniques were used to detect the colonic intestinal microbiota and metabolite profiles, respectively. Correlation analyses was performed to clarify the interactions between differential bacteria, metabolites and M1/M2 macrophages, and pseudo sterile mice were constructed by depletion of gut flora with quadruple antibiotics, followed by faecal microbial transplantation to evaluate its effects on colitis and M1/M2 macrophage polarisation.<br><br>RESULTS: FN dose-dependently alleviated clinical symptoms and inflammatory injury in colonic tissues of colitis mice, with its high-dose efficacy comparable to that of 5-ASA. Concurrently, FN not only inhibited inflammatory infiltration of macrophages and their M1/M2 polarisation balance in colitis mice, but also improved the composition of colonic microbiota and metabolite profiles. However, FN lost its protective effects against DSS-induced colitis and failed to restore the equilibrium of M1/M2 macrophage differentiation following intestinal flora depletion through quadruple antibiotic treatment. Importantly, fecal microbiota transplantation from FN-treated mice restored FN's protective effects against DSS-induced colitis and reestablished its regulatory role in M1/M2 macrophage polarization.<br><br>CONCLUSION: Collectively, FN ameliorated UC through modulating the balance of M1/M2 macrophage polarization in a gut microbiota-dependent manner.}, }
@article {pmid39421003, year = {2024}, author = {Hansen, MM and Rågård, N and Andreasen, PW and Paaske, SE and Dahlerup, JF and Mikkelsen, S and Erikstrup, C and Baunwall, SMD and Hvas, CL}, title = {Encapsulated donor faeces for faecal microbiota transplantation: the Glyprotect protocol.}, journal = {Therapeutic advances in gastroenterology}, volume = {17}, number = {}, pages = {17562848241289065}, pmid = {39421003}, issn = {1756-283X}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection. Its use is backed by solid evidence, but application methods differ. Encapsulated FMT is a non-invasive, patient-friendly and scalable application method that may be preferred over colonoscopy or nasoduodenal tube application.<br><br>OBJECTIVES: We describe a detailed protocol, the Glyprotect protocol, for producing glycerol-based capsules to increase FMT accessibility.<br><br>DESIGN: Using iterative quality improvement methods, we developed and validated the Glyprotect protocol as a reproducible protocol for cryopreserving minimally processed donor faeces in a standard hospital laboratory setting.<br><br>METHODS: We describe detailed standard operating procedures for producing glycerol-based capsules, including all necessary materials and troubleshooting guidelines. Capsule integrity was tested at various temperatures and pH levels. Flow cytometry was used to measure microbiota counts and dose accuracy.<br><br>RESULTS: The Glyprotect protocol has been used for more than 2500 capsule-based FMT treatments and complies with European tissue and cell standards. The protocol is optimised to preserve microbes and minimise modulation of the donated microbiota by removing debris and water, which also reduces the number of capsules needed per FMT treatment. The intestinal microbiota is preserved in glycerol for cryoprotection and to prevent capsule leakage. Each capsule contains 650&#x2009;&#xb5;L microbe-glycerol mass, estimated to contain an average of 2.5&#x2009;&#xd7;&#x2009;10[8] non-specified bacteria.<br><br>CONCLUSION: The Glyprotect protocol enables hospitals and tissue establishments to set up capsule production in a standard laboratory, improving patients' access to FMT. The protocol facilitates the scalability of FMT services because capsule FMT is less time-consuming and less expensive than liquid-suspension FMT applied by colonoscopy or nasojejunal tube.<br><br>TRIAL REGISTRATION: Not applicable.}, }
@article {pmid39420836, year = {2024}, author = {Qu, W and Xu, Y and Yang, J and Shi, H and Wang, J and Yu, X and Chen, J and Wang, B and Zhuoga, D and Luo, M and Liu, R}, title = {Berberine alters the gut microbiota metabolism and impairs spermatogenesis.}, journal = {Acta biochimica et biophysica Sinica}, volume = {57}, number = {4}, pages = {569-581}, pmid = {39420836}, issn = {1745-7270}, mesh = {Male ; *Gastrointestinal Microbiome/drug effects ; *Berberine/pharmacology ; Animals ; *Spermatogenesis/drug effects ; Mice ; Testosterone/blood ; Testis/drug effects/metabolism ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; }, abstract = {Berberine (BBR) is used to treat diarrhea clinically. However, its reproductive toxicity is unclear. This study aims to investigate the impact of BBR on the male reproductive system. Intragastric BBR administration for 14 consecutive days results in a significant decrease in the serum testosterone concentration, epididymal sperm concentration, mating rate and fecundity of male mice. Testicular treatment with testosterone propionate (TP) partially reverses the damage caused by BBR to the male reproductive system. Mechanistically, the decrease in Muribaculaceae abundance in the gut microbiota of mice is the principal cause of the BBR-induced decrease in the sperm concentration. Both fecal microbiota transplantation (FMT) and polyethylene glycol (PEG) treatment demonstrate that Muribaculaceae is necessary for spermatogenesis. The intragastric administration of Muribaculaceae intestinale to BBR-treated mice restores the sperm concentration and testosterone levels. Metabolomic analysis reveals that BBR affects arginine and proline metabolism, of which ornithine level is downregulated. Combined analysis via 16S rRNA metagenomics sequencing and metabolomics shows that Muribaculaceae regulates ornithine level. The transcriptomic results of the testes indicate that the expressions of genes related to the low-density lipoprotein receptor (LDLR)-mediated testosterone synthesis pathway decrease after BBR administration. The transcriptional activity of the Ldlr gene in TM3 cells is increased with increased ornithine supplementation in the culture media, leading to increased testosterone synthesis. Overall, this study reveals an association between a BBR-induced decrease in Muribaculaceae abundance and defective spermatogenesis, providing a prospective therapeutic approach for addressing infertility-related decreases in serum testosterone triggered by changes in the gut microbiota composition.}, }
@article {pmid39420603, year = {2024}, author = {Poupard, L and Page, G and Thoreau, V and Kaouah, Z}, title = {Relationships between Gut Microbiota and Autism Spectrum Disorders: Development and Treatment.}, journal = {Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology}, volume = {22}, number = {4}, pages = {554-564}, pmid = {39420603}, issn = {1738-1088}, abstract = {Many studies have demonstrated the impact of intestinal microbiota on normal brain development. Moreover, the gut microbiota (GM) is impacted by multiple endogenous and environmental factors that may promote gut dysbiosis (GD). An increasing number of studies are investigating the possible role of the GD in the development of neurological and behavioral disorders. For autism spectrum disorders (ASD), specific intestinal bacterial signatures have been identified, knowing that gastrointestinal symptoms are frequently found in ASD. In this review, the peri and post-natal factors modulating the GM are described and the specific gut bacterial signature of ASD children is detailed. Through bidirectional communication between the GM and the brain, several mechanisms are involved in the development of ASD, such as cytokine-mediated neuroinflammation and decreased production of neuroprotective factors such as short-chain fatty acids by the GM. Imbalance of certain neurotransmitters such as serotonin or gamma-aminobutyric acid could also play a role in these gut-brain interactions. Some studies show that this GD in ASD is partly reversible by treatment with pre- and probiotics, or fecal microbiota transplantation with promising results. However, certain limitations have been raised, in particular concerning the short duration of treatment, the small sample sizes and the diversity of protocols. The development of standardized therapeutics acting on GD in large cohort could rescue the gastrointestinal symptoms and behavioral impairments, as well as patient management.}, }
@article {pmid39420082, year = {2024}, author = {Zhang, HJ and Wang, HW and Tian, FY and Yang, CZ and Zhao, M and Ding, YX and Wang, XY and Cui, XY}, title = {Decolonization strategies for ESBL-producing or carbapenem-resistant Enterobacterales carriage: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {24349}, pmid = {39420082}, issn = {2045-2322}, support = {2024L090//Shanxi Provincial Education Department/ ; 2017041037-2//Shanxi Provincial Science and Technology Department/ ; 202303021211121//Natural Science Foundation of Shanxi Province/ ; }, mesh = {Humans ; Anti-Bacterial Agents/therapeutic use/pharmacology ; *beta-Lactamases/metabolism ; *Carbapenem-Resistant Enterobacteriaceae/drug effects/enzymology ; Carbapenems/therapeutic use/pharmacology ; *Carrier State/microbiology/drug therapy ; Enterobacteriaceae/drug effects ; *Enterobacteriaceae Infections/drug therapy/microbiology ; }, abstract = {The prevalence of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE) has become a global public health problem. ESBL-E/CRE colonization can increase the risk of infection in patients and lead to poor disease prognosis. We conducted a systematic review and meta-analysis to evaluate current decolonization strategies regarding ESBL-E/CRE and their efficacy. A literature search was conducted until August 2023 on the five databases to review decolonization strategies associated with ESBL-E/CRE. A meta-analysis was conducted using RevMan 5.4 to compare differences in the decolonization strategy with placebo controls. The primary outcome was decolonization rates, with secondary outcomes of attributable death and adverse events. Quality of identified studies was determined using the Newcastle-Ottawa scale and cochrane risk assessment tool. Random and fixed effects meta-analyses were performed to calculate pooled value. A total of 25 studies were included. In five randomized controlled trial (RCT) studies, the decolonization effect of selective digestive decontamination(SDD) on ESBL-E/CRE at the end of treatment was significantly better in the experimental group than the controls [risk radio (RR): 3.30; 95% CI 1.78-6.14]. In three n-RCT studies, the decolonization effect in the experimental group was still better than the controls one month after SDD therapy [odds ratio (OR): 4.01; 95% CI 1.88-8.56]. The combined decolonization rates reported by six single-arm trial studies of SDD therapy ranged from 53.8 to 68.0%. Additionally, TSA analysis confirmed the effectiveness of SDD therapy. In studies on Faecal microbiota transplantation (FMT) therapy, the decolonization effect of the experimental group was significantly better than the controls 1 month after treatment (OR: 2.57; 95% CI 1.07-6.16). In studies without a control group and with varying follow-up times, the decolonization rates varied widely but indicated the effectiveness trend of FMT therapy (61.3-81.2%). Currently, research on the decolonization effect of probiotic therapy on ESBL-E/CRE is insufficient, and only a systematic review was conducted. SDD and FMT strategies have short-term benefits for ESBL-E/CRE decolonization, but long-term effects are unclear. The effect of probiotic therapy on ESBL-E/CRE decolonization is an interesting topic that still requires further investigation.}, }
@article {pmid39420033, year = {2024}, author = {Majzoub, ME and Paramsothy, S and Haifer, C and Parthasarathy, R and Borody, TJ and Leong, RW and Kamm, MA and Kaakoush, NO}, title = {The phageome of patients with ulcerative colitis treated with donor fecal microbiota reveals markers associated with disease remission.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8979}, pmid = {39420033}, issn = {2041-1723}, support = {988415//Crohn&apos;s and Colitis Foundation (Crohn&apos;s &amp; Colitis Foundation)/ ; APP2011047//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Investigator grant//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Scientia fellowship//University of New South Wales (UNSW Australia)/ ; }, mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology/virology ; *Fecal Microbiota Transplantation ; *Bacteriophages/genetics/isolation &amp; purification/physiology ; *Gastrointestinal Microbiome/genetics ; *Feces/microbiology/virology ; Double-Blind Method ; Male ; Female ; Metagenomics/methods ; Adult ; Dysbiosis/microbiology/therapy ; Middle Aged ; Virome/genetics ; Remission Induction ; Anti-Bacterial Agents/therapeutic use ; Biomarkers ; }, abstract = {Bacteriophages are influential within the human gut microbiota, yet they remain understudied relative to bacteria. This is a limitation of studies on fecal microbiota transplantation (FMT) where bacteriophages likely influence outcome. Here, using metagenomics, we profile phage populations - the phageome - in individuals recruited into two double-blind randomized trials of FMT in ulcerative colitis. We leverage the trial designs to observe that phage populations behave similarly to bacterial populations, showing temporal stability in health, dysbiosis in active disease, modulation by antibiotic treatment and by FMT. We identify a donor bacteriophage putatively associated with disease remission, which on genomic analysis was found integrated in a bacterium classified to Oscillospiraceae, previously isolated from a centenarian and predicted to produce vitamin B complex except B12. Our study provides an in-depth assessment of phage populations during different states and suggests that bacteriophage tracking has utility in identifying determinants of disease activity and resolution.}, }
@article {pmid39418776, year = {2024}, author = {Xie, Q and Sun, J and Sun, M and Wang, Q and Wang, M}, title = {Perturbed microbial ecology in neuromyelitis optica spectrum disorder: Evidence from the gut microbiome and fecal metabolome.}, journal = {Multiple sclerosis and related disorders}, volume = {92}, number = {}, pages = {105936}, doi = {10.1016/j.msard.2024.105936}, pmid = {39418776}, issn = {2211-0356}, mesh = {*Neuromyelitis Optica/microbiology/immunology ; Humans ; *Gastrointestinal Microbiome/physiology ; *Feces/microbiology ; Animals ; Female ; Adult ; *Fecal Microbiota Transplantation ; Mice ; Male ; Metabolome/physiology ; Middle Aged ; }, abstract = {BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating immune-mediated ailment, which is influenced by genetic, epigenetic, and environmental elements. The escalating incidence of NMOSD in recent years implies alterations in environmental risk factors. Recent research has established a correlation between gut microbiomes and the development of NMOSD.<br><br>METHODS: Metagenomic shotgun sequencing and gas chromatography-mass spectrometry (GC-MS) were employed to assess alterations of the structure and function in the fecal microbiome, as well as levels of short-chain fatty acids (SCFAs) in fecal and blood samples, among individuals with neuromyelitis optica spectrum disorder (NMOSD) during the acute phase (n = 25), the remission phase (n = 11), and a group of healthy controls (HCs) (n = 24). We further explored the correlation between gut microbiota and the pathogenesis of NMOSD through fecal microbiota transplantation (FMT). The gut microbiome from human donors diagnosed with NMOSD or HCs was transplanted into germ-free mice, followed by an analysis of the alterations in the structure and functionality of the transplanted mice's gut microbiome. Additionally, the impact of microbiome transfer on the immunity and spinal cord of germ-free mice was assessed through various techniques, including ELISA, flow cytometry, western blot, histopathology, and transcriptome sequencing.<br><br>RESULTS: (1) At the taxonomic levels of genus and species, there were significant differences in the &#x3b1;-diversity of the microbiome between HCs and NMOSD patients in the acute phase, with NMOSD patients having higher species diversity. (2) In the acute phase, the gut microbiota of NMOSD patients was characterized by Ruminococcaceae_unclassified, Campylobacter, Parabacteroides, Lactobacillus, Akkermansia, Streptococcus oralis, Clostridium leptum, Clostridium asparagiforme, Firmicutes bacterium CAG 238, and Lactobacillus fermentum. (3) The relative abundances of Coprobacter, Turicimonas, Gemmiger, Enterobacter, Roseburia sp.CAG 471, Veillonella tobetsuensis, Proteobacteria bacterium CAG 139, Ruminococcus bicirculans, Lactococcus lactis, Flavonifractor plautii, and Streptococcus cristatus were notably lower in patients experiencing remission compared to NMOSD patients in the acute phase, On the other hand, the relative abundances of Flavonifractor (P = 0.049) and Clostridium aldenense (P = 0.049) were significantly higher. Following medication, the gut microbiome distribution in NMOSD patients during remission closely resembled that of healthy controls (HCs). (4) Compared with HCs, acetate levels in the feces of patients with NMOSD in the acute phase were significantly lower. (5) In addition, we transplanted feces from NMOSD patients into germ-free mice and revealed a significant increase in the levels of IL-6, IL-17A, and IL-23 in the blood of mice belonging to the NMOSD fecal transplantation (NFMT) group. Additionally, the IL-10 level exhibited a significant reduction. Moreover, the proportion of Th17 cells displayed a significant increase, while the proportion of Treg cells exhibited a significant decrease in the spleens of NFMT mice.<br><br>CONCLUSION: Patients in the acute phase of neuromyelitis optica spectrum disorder (NMOSD) exhibited imbalances in their gut microbiota and a deficiency in short-chain fatty acids (SCFAs). Following drug treatment, the composition of intestinal microbes in NMOSD patients during the remission phase closely resembled that of the healthy control population. The FMT experiment provided evidence of the significant association between intestinal flora and the pathogenesis of NMOSD. Consequently, investigating gut microbiota and identifying novel microbial markers hold promise for the diagnosis and treatment of NMOSD patients.}, }
@article {pmid39412514, year = {2024}, author = {Han, M and Wang, X and Su, L and Pan, S and Liu, N and Li, D and Liu, L and Cui, J and Zhao, H and Yang, F}, title = {Intestinal microbiome dysbiosis increases Mycobacteria pulmonary colonization in mice by regulating the Nos2-associated pathways.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {39412514}, issn = {2050-084X}, support = {242102521045//Science and Technology Research Project of Henan Province/ ; 242102310202//Science and Technology Research Project of Henan Province/ ; LHGJ20230525//Project of Health Commission of Henan Province/ ; Open Project of the Institute of Tuberculosis XYJHB20210//Xinxiang Medical University/ ; Tuberculosis Capacity Improvement Project 2023-68//Henan Provincial Health Commission/ ; }, mesh = {Animals ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome/physiology ; Mice ; *Lung/microbiology ; *Nitric Oxide Synthase Type II/metabolism/genetics ; Mice, Inbred C57BL ; Mycobacterium tuberculosis ; Tuberculosis/microbiology ; }, abstract = {Increasing researches reveal gut microbiota was associated with the development of tuberculosis (TB). How to prevent or reduce Mycobacterium tuberculosis colonization in the lungs is a key measure to prevent TB. However, the data on gut microbiota preventing Mycobacterium colonization in the lungs were scarce. Here, we established the clindamycin-inducing intestinal microbiome dysbiosis and fecal microbial transplantation models in mice to identify gut microbiota's effect on Mycobacterium's colonization in the mouse lungs and explore its potential mechanisms. The results showed that clindamycin treatment altered the diversity and composition of the intestinal bacterial and fungal microbiome, weakened the trans-kingdom network interactions between bacteria and fungi, and induced gut microbiome dysbiosis in the mice. Gut microbiota dysbiosis increases intestinal permeability and enhances the susceptibility of Mycobacterium colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased Nos2 expression through the 'gut-lung axis'. Nos2 high expression disrupts the intracellular antimicrobial and anti-inflammatory environment by increasing the concentration of nitric oxide, decreasing the levels of reactive oxygen species and Defb1 in the cells, and promoting Mycobacteria colonization in the lungs of mice. The present study raises a potential strategy for reducing the risks of Mycobacteria infections and transmission by regulating the gut microbiome balance.}, }
@article {pmid39410876, year = {2024}, author = {Wen, J and Feng, Y and Xue, L and Yuan, S and Chen, Q and Luo, A and Wang, S and Zhang, J}, title = {High-fat diet-induced L-saccharopine accumulation inhibits estradiol synthesis and damages oocyte quality by disturbing mitochondrial homeostasis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2412381}, pmid = {39410876}, issn = {1949-0984}, mesh = {Animals ; Female ; *Diet, High-Fat/adverse effects ; *Estradiol/metabolism/biosynthesis ; *Oocytes/metabolism/drug effects ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Mitochondria/metabolism/drug effects ; *Dysbiosis/microbiology ; *Homeostasis ; *Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Infertility, Female/microbiology/metabolism/etiology ; Ovary/metabolism/microbiology ; }, abstract = {High-fat diet (HFD) has been linked to female infertility. However, the specific age at which HFD impacts ovarian function and the underlying mechanisms remain poorly understood. Here, we administered a HFD to female mice at various developmental stages: pre-puberty (4 weeks old), post-puberty (6 weeks old), young adult (9 weeks old), and middle age (32 weeks old). Our observations indicated that ovarian function was most significantly compromised when HFD was initiated at post-puberty. Consequently, post-puberty mice were chosen for further investigation. Through transplantation of fecal bacteria from the HFD mice to the mice on a normal diet, we confirmed that gut microbiota dysbiosis contributed to HFD-induced deteriorated fertility and disrupted estradiol synthesis. Utilizing untargeted and targeted metabolomics analyses, we identified L-saccharopine as a key metabolite, which was enriched in the feces, serum, and ovaries of HFD and HFD-FMT mice. Subsequent in vitro and in vivo experiments demonstrated that L-saccharopine disrupted mitochondrial homeostasis by impeding AMPKα/MFF-mediated mitochondrial fission. This disruption ultimately hindered estradiol synthesis and compromised oocyte quality. AICAR, an activator of AMPKα, ameliorated L-saccharopine induced mitochondrial damage in granulosa cells and oocytes, thereby enhancing E2 synthesis and improving oocyte quality. Collectively, our findings indicate that the accumulation of L-saccharopine may play a pivotal role in mediating HFD-induced ovarian dysfunction. This highlights the potential therapeutic benefits of targeting the gut microbiota-metabolite-ovary axis to address HFD-induced ovarian dysfunction.}, }
@article {pmid39409832, year = {2024}, author = {Kang, HJ and Kim, SW and Kim, SM and La, TM and Hyun, JE and Lee, SW and Kim, JH}, title = {Altered Gut Microbiome Composition in Dogs with Hyperadrenocorticism: Key Bacterial Genera Analysis.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {19}, pages = {}, pmid = {39409832}, issn = {2076-2615}, abstract = {Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, which is associated with diverse metabolic abnormalities. We hypothesized that elevated cortisol levels in dogs with HAC disrupt the gut microbiome (GM), and this disruption persists even after trilostane treatment. This study explored GM composition in dogs with HAC. We included 24 dogs, 15 with HAC and 9 healthy controls, and followed up with 5 dogs with HAC who received trilostane treatment. The GM analysis revealed significant compositional changes in dogs with HAC, including reduced microbiome diversity compared to healthy controls, particularly in rare taxa, as indicated by the Shannon index (p = 0.0148). Beta diversity analysis further showed a distinct clustering of microbiomes in dogs with HAC, separating them from healthy dogs (p < 0.003). Specifically, an overrepresentation of Proteobacteria (Pseudomonadota), Actinobacteria, Bacteroides, Enterococcus, Corynebacterium, Escherichia, and Proteus populations occurred alongside a decreased Firmicutes (Bacillota) population. Despite trilostane treatment, gut dysbiosis persisted in dogs with HAC at a median of 41 d post treatment, suggesting its potential role in ongoing metabolic issues. We identified GM dysbiosis in dogs with HAC by examining key bacterial genera, offering insights into potential interventions like probiotics or fecal microbiota transplants for better HAC management.}, }
@article {pmid39408940, year = {2024}, author = {Luppi, S and Aldegheri, L and Azzalini, E and Pacetti, E and Barucca Sebastiani, G and Fabiani, C and Robino, A and Comar, M}, title = {Unravelling the Role of Gut and Oral Microbiota in the Pediatric Population with Type 1 Diabetes Mellitus.}, journal = {International journal of molecular sciences}, volume = {25}, number = {19}, pages = {}, pmid = {39408940}, issn = {1422-0067}, support = {RC 26/22 (Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy)//Ministero della Salute/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 1/microbiology ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology ; Child ; Mouth/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; Microbiota ; }, abstract = {Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease that results in the destruction of pancreatic β cells, leading to hyperglycaemia and the need for lifelong insulin therapy. Although genetic predisposition and environmental factors are considered key contributors to T1DM, the exact causes of the disease remain partially unclear. Recent evidence has focused on the relationship between the gut, the oral cavity, immune regulation, and systemic inflammation. In individuals with T1DM, changes in the gut and oral microbial composition are commonly observed, indicating that dysbiosis may contribute to immune dysregulation. Gut dysbiosis can influence the immune system through increased intestinal permeability, altered production of short chain fatty acids (SCFAs), and interactions with the mucosal immune system, potentially triggering the autoimmune response. Similarly, oral dysbiosis may contribute to the development of systemic inflammation and thus influence the progression of T1DM. A comprehensive understanding of these relationships is essential for the identification of biomarkers for early diagnosis and monitoring, as well as for the development of therapies aimed at restoring microbial balance. This review presents a synthesis of current research on the connection between T1DM and microbiome dysbiosis, with a focus on the gut and oral microbiomes in pediatric populations. It explores potential mechanisms by which microbial dysbiosis contributes to the pathogenesis of T1DM and examines the potential of microbiome-based therapies, including probiotics, prebiotics, synbiotics, and faecal microbiota transplantation (FMT). This complex relationship highlights the need for longitudinal studies to monitor microbiome changes over time, investigate causal relationships between specific microbial species and T1DM, and develop personalised medicine approaches.}, }
@article {pmid39408584, year = {2024}, author = {Guevara-Ramírez, P and Cadena-Ullauri, S and Paz-Cruz, E and Ruiz-Pozo, VA and Tamayo-Trujillo, R and Cabrera-Andrade, A and Zambrano, AK}, title = {Gut Microbiota Disruption in Hematologic Cancer Therapy: Molecular Insights and Implications for Treatment Efficacy.}, journal = {International journal of molecular sciences}, volume = {25}, number = {19}, pages = {}, pmid = {39408584}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hematologic Neoplasms/therapy/microbiology ; Probiotics/therapeutic use ; Treatment Outcome ; Antineoplastic Agents/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Hematologic malignancies (HMs), including leukemia, lymphoma, and multiple myeloma, involve the uncontrolled proliferation of abnormal blood cells, posing significant clinical challenges due to their heterogeneity and varied treatment responses. Despite recent advancements in therapies that have improved survival rates, particularly in chronic lymphocytic leukemia and acute lymphoblastic leukemia, treatments like chemotherapy and stem cell transplantation often disrupt gut microbiota, which can negatively impact treatment outcomes and increase infection risks. This review explores the complex, bidirectional interactions between gut microbiota and cancer treatments in patients with HMs. Gut microbiota can influence drug metabolism through mechanisms such as the production of enzymes like bacterial β-glucuronidases, which can alter drug efficacy and toxicity. Moreover, microbial metabolites like short-chain fatty acids can modulate the host immune response, enhancing treatment effectiveness. However, therapy often reduces the diversity of beneficial bacteria, such as Bifidobacterium and Faecalibacterium, while increasing pathogenic bacteria like Enterococcus and Escherichia coli. These findings highlight the critical need to preserve microbiota diversity during treatment. Future research should focus on personalized microbiome-based therapies, including probiotics, prebiotics, and fecal microbiota transplantation, to improve outcomes and quality of life for patients with hematologic malignancies.}, }
@article {pmid39407442, year = {2024}, author = {Lamminpää, I and Niccolai, E and Amedei, A}, title = {Probiotics as adjuvants to mitigate adverse reactions and enhance effectiveness in Food Allergy Immunotherapy.}, journal = {Scandinavian journal of immunology}, volume = {100}, number = {6}, pages = {e13405}, doi = {10.1111/sji.13405}, pmid = {39407442}, issn = {1365-3083}, mesh = {Humans ; *Probiotics/therapeutic use ; *Food Hypersensitivity/therapy/immunology ; *Desensitization, Immunologic/methods/adverse effects ; *Adjuvants, Immunologic/therapeutic use ; *Allergens/immunology ; *Gastrointestinal Microbiome/immunology ; Animals ; T-Lymphocytes, Regulatory/immunology ; Immunoglobulin E/immunology ; }, abstract = {In the past decades, food allergies became increasingly dominant since early childhood, leading to a lower quality of life and to increasing costs addressed by the health care system. Beside standard avoidance of specific allergens and drug treatments following allergen exposure, a great deal of research has lately focused on Food Allergy Allergen Immunotherapy (FA-AIT). SCIT and EPIT (Subcutaneous and Epicutaneous Immunotherapy), OIT (Oral Immunotherapy), and SLIT (Sublingual Immunotherapy) consist in gradual exposure to allergens to desensitize and achieve tolerance once therapy has ended. Although promising, FA-AIT may bring acute local and systemic adverse reactions. To enhance efficacy, safety and convenience of AIT, the quest of potential adjuvants to mitigate the adverse reactions becomes crucial. Immunomodulatory activities, such as that of increasing the regulatory T cells and decreasing the IgE, have been observed in specific probiotics' strains and multiple studies elucidated the role of gut microbiota as a major interplayer among the host and its immune system. In this review, the microbiome modulation is shown as potential AIT adjuvant, nevertheless the need of more clinical studies in the near future is pivotal to assess the efficacy of targeted bacterial therapies and faecal microbiota transplantation.}, }
@article {pmid39407244, year = {2024}, author = {Huang, Y and Wang, Y and Huang, X and Yu, X}, title = {Unveiling the overlooked fungi: the vital of gut fungi in inflammatory bowel disease and colorectal cancer.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {59}, pmid = {39407244}, issn = {1757-4749}, support = {NSFC 32260024, 32060040//the National Natural Science Foundation of China/ ; 20232BAB216091, 20202BAB206062//The Jiangxi Natural Science Foundation/ ; jxsq2023201019//The Double-Thousand Talent Program of Jiangxi Province/ ; }, abstract = {The fungi of the human microbiota play important roles in the nutritional metabolism and immunological balance of the host. Recently, research has increasingly emphasised the role of fungi in modulating inflammation in intestinal diseases and maintaining health in this environment. It is therefore necessary to understand more clearly the interactions and mechanisms of the microbiota/pathogen/host relationship and the resulting inflammatory processes, as well as to offer new insights into the prevention, diagnosis and treatment of inflammatory bowel disease (IBD), colorectal cancer (CRC) and other intestinal pathologies. In this review, we comprehensively elucidate the fungal-associated pathogenic mechanisms of intestinal inflammation in IBD and related CRC, with an emphasis on three main aspects: the direct effects of fungi and their metabolites on the host, the indirect effects mediated by interactions with other intestinal microorganisms and the immune regulation of the host. Understanding these mechanisms will enable the development of innovative approaches based on the use of fungi from the resident human microbiota such as dietary interventions, fungal probiotics and faecal microbiota transplantation in the prevention, diagnosis and treatment of intestinal diseases.}, }
@article {pmid39406549, year = {2024}, author = {Li, K and Guo, L and Yu, J and Yang, Y and Wei, L and Min, C and Xu, X and Li, F and Liu, J and Zhou, G and Zhang, J}, title = {Kui-Jie-Ling capsule inhibits ulcerative colitis by modulating inflammation and gut microbiota.}, journal = {Journal of gastroenterology and hepatology}, volume = {39}, number = {12}, pages = {2735-2745}, doi = {10.1111/jgh.16758}, pmid = {39406549}, issn = {1440-1746}, support = {81202882//National Natural Science Foundation of China/ ; SNG2021022//Suzhou Science and Technology Planning Project in Jiangsu Province of China/ ; SYS2020079//Suzhou Science and Technology Planning Project in Jiangsu Province of China/ ; Z2020063//Jiangsu Health Commission Medical Research Projects, China/ ; JCZ21130//Science and Technology Bureau of Haian City, China/ ; SZWZYTD202205//Scientific and Technological Innovation Team Building Program of Suzhou Vocational Health College/ ; PAPD//Priority Academic Program Development of the Jiangsu Higher Education Institutes, China/ ; SZWZY202401//Science and Technology Planning Project of Suzhou Vocational Health College/ ; }, mesh = {Animals ; *Colitis, Ulcerative/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Disease Models, Animal ; *Adalimumab/administration &amp; dosage ; *Drugs, Chinese Herbal/administration &amp; dosage/pharmacology ; Dextran Sulfate ; Male ; Capsules ; Colon/microbiology/pathology ; Cytokines/metabolism ; Fecal Microbiota Transplantation ; Mice ; Mice, Inbred C57BL ; Anti-Inflammatory Agents/administration &amp; dosage ; Inflammation/prevention &amp; control ; NF-kappa B/metabolism ; Drug Therapy, Combination ; }, abstract = {BACKGROUND AND AIM: Kui-Jie-Ling capsule (Kui-Jie-Ling) is a hospital preparation for ulcerative colitis (UC) in China. This study aimed at evaluating the protective effects and mechanisms of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab on UC induced by dextran sulfate sodium (DSS).<br><br>METHODS: Network pharmacology was combined with an animal experiment to reveal the targets of Kui-Jie-Ling alleviating UC. The UC model was established by drinking 2.5% DSS solution for 7&#xa0;days. On the second day, the mice in the Kui-Jie-Ling group were orally administered with Kui-Jie-Ling (1.5 and 3.0&#xa0;g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui-Jie-Ling (3.0&#xa0;g/kg) once a day for seven consecutive days and received one subcutaneous injection of adalimumab. The disease activity index, the colon length, the spleen index, the cytokines, the colon, the short-chain fatty acid content, and the gut microbiota in the colon were analyzed. The role of gut microbiota against UC was verified by fecal microbiota transplantation experiments.<br><br>RESULTS: The animal study's results were consistent with the network pharmacology analysis, which reflected that Kui-Jie-Ling alleviated UC via multi-pathway. Kui-Jie-Ling ameliorated UC by inhibiting the formation of neutrophil extracellular traps (NETs), regulating inflammatory factors through the lipopolysaccharide-toll-like receptor 4/nuclear factor kappa B and interleukin-23-Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, and restoring intestinal homeostasis.<br><br>CONCLUSION: These studies provided the experimental basis for the clinical administration of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab against UC.}, }
@article {pmid39404715, year = {2024}, author = {Maev, IV and Velikolug, KA}, title = {[Cytomegalovirus infection in gastroenterology].}, journal = {Terapevticheskii arkhiv}, volume = {96}, number = {8}, pages = {723-731}, doi = {10.26442/00403660.2024.08.202814}, pmid = {39404715}, issn = {0040-3660}, mesh = {Humans ; *Cytomegalovirus Infections/diagnosis/drug therapy ; *Antiviral Agents/therapeutic use ; Cytomegalovirus/genetics/isolation &amp; purification ; Gastrointestinal Diseases/virology/diagnosis/therapy/etiology ; Risk Factors ; Polymerase Chain Reaction/methods ; DNA, Viral/analysis ; }, abstract = {AIM: To highlight the relevance of gastrointestinal manifestations of cytomegalovirus infection (CMVI), to highlight the main risk factors for the development of this pathology, current trends in diagnosis and treatment.<br><br>KEY POINTS: CMVI is one of the most common opportunistic diseases, characterized by a variety of manifestations from asymptomatic to severe generalized forms affecting internal organs and body systems. The prevalence of CMVI worldwide ranges from 20 to 95%. Particular attention is paid to timely diagnosis, treatment and prevention of CMVI. The "gold standard" in the diagnosis of digestive diseases associated with CMVI is immunohistochemical examination and detection of cytomegalovirus (CMV) DNA in tissues using the polymerase chain reaction (PCR). Of undoubted interest in the diagnosis of CMV is the detection of CMV DNA in stool using digital PCR. Compared to quantitative PCR, digital PCR has higher accuracy and sensitivity. As first-line therapy, the drugs of choice are ganciclovir and valganciclovir. Maribavir has been successfully used to treat patients with CMV infection refractory to one or more previous therapies. One of the promising directions in the treatment of cytomegalovirus colitis in patients with ulcerative colitis is fecal microbiota transplantation.<br><br>CONCLUSION: Timely identification of risk factors for the development of CMV infection, the introduction of innovative methods and approaches in diagnosis, and the use of effective methods for treating diseases of the digestive system associated with CMV infection can improve the prognosis of the underlying disease and reduce the risk of developing urgent conditions in gastroenterology.}, }
@article {pmid39403342, year = {2024}, author = {Bertin, L and Crepaldi, M and Zanconato, M and Lorenzon, G and Maniero, D and De Barba, C and Bonazzi, E and Facchin, S and Scarpa, M and Ruffolo, C and Angriman, I and Buda, A and Zingone, F and Savarino, EV and Barberio, B}, title = {Refractory Crohn's Disease: Perspectives, Unmet Needs and Innovations.}, journal = {Clinical and experimental gastroenterology}, volume = {17}, number = {}, pages = {261-315}, pmid = {39403342}, issn = {1178-7023}, abstract = {Crohn's disease (CD) is a complex, chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. Despite advances in treatment, CD remains a significant health burden, leading to substantial direct healthcare costs and out-of-pocket expenses for patients, especially in the first-year post-diagnosis. The impact of CD on patients' quality of life is profound, with significant reductions in physical, emotional, and social well-being. Despite advancements in therapeutic options, including biologics, immunomodulators, and small molecules, many patients struggle to achieve or maintain remission, leading to a considerable therapeutic ceiling. This has led to an increased focus on novel and emerging treatments. This context underscores the importance of exploring advanced and innovative treatment options for managing refractory CD. By examining the latest approaches, including immunomodulators, combination therapies, stem cell therapies, and emerging treatments like fecal microbiota transplantation and dietary interventions, there is an opportunity to gain a comprehensive understanding of how best to address and manage refractory cases of CD.}, }
@article {pmid39403201, year = {2024}, author = {Napiórkowska-Baran, K and Biliński, J and Pujanek, M and Hałakuc, P and Pietryga, A and Szymczak, B and Deptuła, A and Rosada, T and Bartuzi, Z}, title = {Fecal microbiota transplantation in a patient with chronic diarrhea and primary and secondary immunodeficiency (common variable immunodeficiency and splenectomy).}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1456672}, pmid = {39403201}, issn = {2235-2988}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Diarrhea/microbiology/therapy ; Middle Aged ; *Splenectomy ; *Common Variable Immunodeficiency/complications/therapy ; *Gastrointestinal Microbiome ; Feces/microbiology/virology ; Cytomegalovirus Infections ; Male ; Treatment Outcome ; Valganciclovir/therapeutic use/administration &amp; dosage ; Chronic Disease ; Immunocompromised Host ; Dysbiosis/therapy/microbiology ; Clostridioides difficile ; }, abstract = {The gut microbiota serves a crucial role in the development of host immunity. Immunocompromised patients are particularly vulnerable to dysbiosis not only by virtue of a defect in the immune system but also due to increased susceptibility to infection and multiple courses of antibiotic therapy. Fecal microbiota transplantation is by far the most effective option for restoring gastrointestinal homeostasis. However, it is contraindicated in patients with significant primary and secondary immunodeficiencies. This article presents the case of a 59-year-old patient with common variable immunodeficiency, after splenectomy at age 39 for primary immune thrombocytopenia, who manifested diarrhea of up to 10 stools per day accompanied by secondary malnutrition and cachexia. The patient was admitted to the hospital on multiple occasions due to this condition, with stool PCR tests confirming a HHV-5 (Cytomegalovirus, CMV) infection. Following the administration of valganciclovir, the patient's complaints diminished, although, upon cessation of the drug, the symptoms recurred. In addition, the patient had an intestinal infection with C. difficile etiology. Given that the patient's therapeutic options had been exhausted, after obtaining informed consent from the patient and approval from the bioethics committee to conduct a medical experiment, treatment of diarrhea was undertaken by fecal microbiota transplantation with the certified preparation Mbiotix HBI from the Human Biome Institute. The patient underwent two transplants, with a one-week interval between them. The initial procedure was performed using the endoscopic method, while the subsequent was conducted using the capsule method. Following the administration of the applied treatment, the patient's symptoms were successfully alleviated, and no adverse effects were observed. A microbiological analysis of the intestinal microbiota was conducted prior to and following transplantation via next-generation sequencing (NGS). No recurrence of symptoms was observed during the two-year follow-up period. To the best of our knowledge, this is the first fecal microbiota transplantation in an adult patient with primary and secondary immunodeficiency.}, }
@article {pmid39403173, year = {2024}, author = {Huang, J and Wang, X and Zhang, J and Li, Q and Zhang, P and Wu, C and Jia, Y and Su, H and Sun, X}, title = {Fecal microbiota transplantation alleviates food allergy in neonatal mice via the PD-1/PD-L1 pathway and change of the microbiota composition.}, journal = {The World Allergy Organization journal}, volume = {17}, number = {10}, pages = {100969}, pmid = {39403173}, issn = {1939-4551}, abstract = {BACKGROUND: Food allergy (FA) is a common disorder in children and affects the health of children worldwide. The gut microbiota is closely related to the occurrence and development of FA. Fecal microbiota transplantation (FMT) is a way to treat diseases by reconstituting the microbiota; however, the role and mechanisms of FA have not been validated.<br><br>METHODS: In this study, we established an ovalbumin (OVA)-induced juvenile mouse model and used 16S RNA sequencing, pathological histological staining, molecular biology, and flow-through techniques to evaluate the protective effects of FMT treatment on FA and to explore the mechanisms.<br><br>RESULTS: OVA-induced dysregulation of the gut microbiota led to impaired intestinal function and immune dysregulation in FA mice. FMT treatment improved the structure, diversity, and composition of the gut microbiota and restored it to a near-donor state. FMT treatment reduced levels of Th2-associated inflammatory factors, decreased intestinal tissue inflammation, and reduced IgE production. In addition, FMT reduced the number of mast cells and eosinophils and suppressed OVA-specific antibodies. Further mechanistic studies revealed that FMT treatment induced immune tolerance by inducing the expression of CD103[+]DCs and programmed cell death ligand 1 (PD-L1) in mesenteric lymph nodes and promoting the production of Treg through the programmed cell death protein 1 (PD-1)/PD-L1 pathway. Meanwhile, Th2 cytokines, OVA-specific antibodies, and PD-1/PD-L1 showed a significant correlation with the gut microbiota.<br><br>CONCLUSIONS: FMT could regulate the gut microbiota and Th1/Th2 immune balance and might inhibit FA through the PD-1/PD-L1 pathway, which would provide a new idea for the treatment of FA.}, }
@article {pmid39403057, year = {2024}, author = {Liang, C and Pereira, R and Zhang, Y and Rojas, OL}, title = {Gut Microbiome in Alzheimer's Disease: from Mice to Humans.}, journal = {Current neuropharmacology}, volume = {22}, number = {14}, pages = {2314-2329}, pmid = {39403057}, issn = {1875-6190}, mesh = {*Alzheimer Disease/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Humans ; Animals ; *Brain-Gut Axis/physiology ; Mice ; Probiotics/therapeutic use ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Prebiotics ; }, abstract = {Alzheimer's disease (AD) is the most prevalent type of dementia, but its etiopathogenesis is not yet fully understood. Recent preclinical studies and clinical evidence indicate that changes in the gut microbiome could potentially play a role in the accumulation of amyloid beta. However, the relationship between gut dysbiosis and AD is still elusive. In this review, the potential impact of the gut microbiome on AD development and progression is discussed. Pre-clinical and clinical literature exploring changes in gut microbiome composition is assessed, which can contribute to AD pathology including increased amyloid beta deposition and cognitive impairment. The gut-brain axis and the potential involvement of metabolites produced by the gut microbiome in AD are also highlighted. Furthermore, the potential of antibiotics, prebiotics, probiotics, fecal microbiota transplantation, and dietary interventions as complementary therapies for the management of AD is summarized. This review provides valuable insights into potential therapeutic strategies to modulate the gut microbiome in AD.}, }
@article {pmid39401017, year = {2024}, author = {Yang, T and Liu, Y and Yin, J and Yv, T and Zhou, F and Li, Y and Yang, L and Han, L and Huang, X}, title = {Transplantation of fecal microbiota from different breeds improved intestinal barrier condition and modulated ileal microflora of recipient pigs.}, journal = {Journal of animal science}, volume = {102}, number = {}, pages = {}, pmid = {39401017}, issn = {1525-3163}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Ileum/microbiology ; Swine ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Intestinal Mucosa/microbiology ; }, abstract = {In this study, we investigated the effects of transplanting Ningxiang pig fecal bacteria on the ileum microflora and intestinal barrier of Duroc × Landrace × Large White (DLY) pigs. Thirty-two DLY pigs at 90-d-old were equally assigned to either control groups (fed the basal diet) or test groups (fed the basal diet + 10 mL fecal microbiota suspension from Ningxiang pig). Results showed that fecal microbiota transplantation (FMT) did not influence the growth performance, but increased the number of ileum goblet cells and the expression level of mucin-2. Additionally, the mucosal levels of anti-inflammatory cytokines interlukin-4 and interlukin-10 were upregulated, but the level of pro-inflammatory cytokine interferon-γ was downregulated by FMT. Moreover, FMT increased the expression level of porcine β defensin-114 in ileum mucus. 16S rRNA gene sequencing of ileal digesta showed that FMT modulated the diversity and composition of ileal microbiota of DLY pigs by increasing the relative abundances of beneficial bacteria, while decreasing the abundance of the pathogenic bacterium Streptococcus. Taken together, the study showed that FMT of Ningxiang pigs could improve the intestinal barrier condition of DLY pigs by improving intestinal microflora and promoting intestinal health.}, }
@article {pmid39400011, year = {2024}, author = {Lu, D and Ji, L and Liu, F and Liu, H and Sun, Z and Yan, J and Wu, H}, title = {Fecal Microbiota Transplantation Induced by Wumei Pills Improves Chemotherapy-Induced Intestinal Mucositis in BALB/c Mice by Modulating the TLR4/MyD88/NF-κB Signaling Pathway.}, journal = {Current drug delivery}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115672018304338241003095955}, pmid = {39400011}, issn = {1875-5704}, abstract = {BACKGROUND: Our previous studies have found that Wumei Pills can regulate the intestinal flora to inhibit chemotherapy-induced intestinal mucositis (CIM). However, there is still insufficient evidence to confirm that intestinal flora is the main link in the regulation of CIM by Wumei Pills, and its downstream mechanism is still unclear.<br><br>METHOD: We first obtained the signal pathway of the intervention of Wumei Pill on CIM through network pharmacological analysis and then transplanted the bacterial solution into CIM mice, combined with Western Blot, HE, ELISA and other biological technology-related proteins and inflammatory factors.<br><br>RESULTS: It showed that 97 kinds of effective ingredients and 205 kinds of targets of Wumei pills were screened out and the potential mechanism of Wumei Pills on CIM may be the NF-&#x3ba;B signaling pathway. In contrast with the control group, the results displayed that the weight, food intake, and mice's colon length were apparently decreased in the 5-Fu group, while the diarrhea score was increased. However, FMT reversed this change, and the difference was statistically significant. Additionally, FMT could improve the pathological state of inflammatory cell infiltration in mice, reduce histopathological scores of colon and jejunum, decrease the expression levels of IL-1&#x3b2;, MPO, TNF-&#x3b1;, and IL-6, reverse the activation of signaling pathway named TLR4/Myd88/ NF-&#x3ba;B and down-regulate protein expression, thereby exerting its anti-inflammatory activities. Further experiments have found that FMT could reverse the decreasing of tight junction proteins and mucins caused by 5-Fu, thereby repairing the intestinal mucosal barrier, and FMT could also increase the content of acetic acid, propanoic acid, and butanoic acid in the feces of 5-Fu group.<br><br>CONCLUSION: FMT can defend the intestinal mucosal barrier integrality by increasing the content of exercise fatty acids, and its mechanism may be in connection with its inhibition of TLR4/My- D88/NF-&#x3ba;B signal pathway to relieve inflammation.}, }
@article {pmid39399248, year = {2024}, author = {Scott, A and Khoruts, A and Freeman, ML and Beilman, G and Ramanathan, K and Bellin, MD and Trikudanathan, G}, title = {Successful Use of Fecal Microbiota Transplantation in Management of Nonobstructive Recurrent Cholangitis Following Total Pancreatectomy and Islet Autotransplant.}, journal = {ACG case reports journal}, volume = {11}, number = {10}, pages = {e01527}, pmid = {39399248}, issn = {2326-3253}, abstract = {Alterations in the gut microbiome have been implicated in various pathologies. Fecal microbiota transplantation (FMT) has been offered as a novel treatment for conditions implicated in the disruption of the gut-microbiota axis. This case report details the successful treatment of recurrent nonobstructive cholangitis following a single FMT application in a patient who had previously undergone a hepatobiliary tract surgical diversion. Cholangitis was suspected secondary to reflux of an altered microbiome into the surgically reanastomosed biliary tract, and FMT was justified based on the history of recurrent Clostridioides difficile infections. This case supports the further evaluation of the utility of FMT as one potential treatment of post hepatobiliary surgical diversion cholangitis.}, }
@article {pmid39398388, year = {2024}, author = {Liu, T and Lei, C and Huang, Q and Song, W and Li, C and Sun, N and Liu, Z}, title = {Hesperidin and Fecal Microbiota Transplantation Modulate the Composition of the Gut Microbiota and Reduce Obesity in High Fat Diet Mice.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {17}, number = {}, pages = {3643-3656}, pmid = {39398388}, issn = {1178-7007}, abstract = {INTRODUCTION: Obesity, which is associated with gut microbiota dysbiosis, low-grade chronic inflammation and intestinal barrier dysfunction, can cause a variety of chronic metabolic diseases. Phytochemical flavonoids have a variety of biological activities, among which there may be safe and effective anti-obesity solutions.<br><br>METHODS: We tested a plant-derived flavonoid hesperidin and fecal microbiota transplantation (FMT) to alleviate diet-induced obesity. High-fat diet (HFD)-fed mice were treated with hesperidin (100 and 200 mg/kg BW) and FMT.<br><br>RESULTS: Results indicated that hesperidin had the effects of reducing obesity as indicated by reduction of body weight, fat accumulation and blood lipids, reducing inflammation as indicated by reduction of pro-inflammation factors including TNF&#x3b1;, IL-6, IL-1&#x3b2;and iNOS, and improving gut integrity as indicated by increasing colon length, reducing plasma gut permeability indicators iFABP and LBP, increased mRNA expression of mucus protein Muc2, tight junction p Claudin 2, Occludin and ZO-1 in the HFD-fed mice. The anti-obesity effects of hesperidin treatment have a dose-dependent manner. In addition, 16S rRNA-based gut microbiota analysis revealed that hesperidin selectively promoted the growth of Lactobacillus salivarius, Staphylococcus sciuri and Desulfovibrio C21_c20 while inhibiting Bifidobacterium pseudolongum, Mucispirillum schaedleri, Helicobacter ganmani and Helicobacter hepaticus in the HFD-fed mice. Horizontal feces transfer from the normal diet (ND)-fed mice to the HFD-fed mice conferred anti-obesity effects and transmitted some of the HFD-modulated microbes.<br><br>CONCLUSION: We concluded that hesperidin and FMT both affect the reduction of body weight and improve HFD-related disorders in the HFD-fed mice possibly through modulating the composition of the gut microbiota.}, }
@article {pmid39397472, year = {2024}, author = {Ding, H and Wang, Q and Liao, G and Hao, Z}, title = {[Diagnosis and treatment of gastrointestinal bleeding after kidney transplantation].}, journal = {Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences}, volume = {56}, number = {5}, pages = {902-907}, pmid = {39397472}, issn = {1671-167X}, mesh = {Humans ; *Kidney Transplantation ; *Gastrointestinal Hemorrhage/etiology/diagnosis/therapy ; Retrospective Studies ; *Kidney Failure, Chronic/therapy/complications ; Gastroscopy ; Male ; Embolization, Therapeutic ; }, abstract = {OBJECTIVE: To analyze the clinical characteristics of acute and chronic gastrointestinal bleeding in patients with end-stage renal disease (ESRD) after kidney transplantation, to improve the understanding of the causes, diagnosis, treatment and prevention of this complication, and to improve the management of patients with gastrointestinal bleeding after kidney transplantation.<br><br>METHODS: The clinical, imaging and pathological data of patients with gastrointestinal bleeding after kidney transplantation in the Department of Urology of The First Affiliated Hospital of Anhui Medical University from August, 2015 to December, 2020 were collected. The etiology, early clinical manifestations, abnormal laboratory tests and examinations, treatment procedures, late prevention and treatment measures and outcomes of gastrointestinal bleeding were retrospectively studied, and the relevant literature was summarized and reviewed.<br><br>RESULTS: A total of 17 patients were included in this study. Nine patients had chronic small amount of bleeding, hemoglobin gradually decreased, melena and fecal occult blood positive in the early stage, and the general condition was good, vital signs were stable, and were cured by drug treatment. Gastroscopy showed small ulcers with active bleeding foci in 2 cases, and the bleeding was stopped by titanium clips, and the prognosis was good. Gastroscopy showed that the anterior wall longitudinal ulcer at the junction of gastric antrum body was not effective in 1 case, and the small branch of right gastroepithelial artery was embolized, and the patient recovered and discharged after 2 weeks. Gastroscopy showed deep pit ulcer at the lesser curvature of gastric antrum in 1 patient, who underwent distal gastroduodenal artery embolization and had a good prognosis. Gastroscopy showed huge multiple ulcers in the stomach and duodenal bulb in 2 patients, who underwent subtotal gastrectomy and partial duodenectomy, duodenal stump exclusion and remnant gastrojejunostomy. One patient recovered and was discharged, and the other patient died of rebleeding on the 12th day after surgery. Two cases of diverticulum underwent surgical resection of diverticulum, and the prognosis was good.<br><br>CONCLUSION: The onset of gastrointestinal hemorrhage in kidney transplant patients is insidious, and the condition is acute or slow, which can cause different degrees of damage to the patient and the transplanted kidney. Active prevention, early diagnosis, timely drug treatment, if the effect is not good, decisive endoscopic titanium clip hemostasis, transvascular interventional embolization, and even surgical treatment can minimize the harm of gastrointestinal bleeding.}, }
@article {pmid39396842, year = {2024}, author = {González, A and Badiola, I and Fullaondo, A and Rodríguez, J and Odriozola, A}, title = {Personalised medicine based on host genetics and microbiota applied to colorectal cancer.}, journal = {Advances in genetics}, volume = {112}, number = {}, pages = {411-485}, doi = {10.1016/bs.adgen.2024.08.004}, pmid = {39396842}, issn = {0065-2660}, mesh = {Humans ; *Colorectal Neoplasms/genetics/microbiology ; *Precision Medicine/methods ; *Gastrointestinal Microbiome/genetics ; Biomarkers, Tumor/genetics ; Prognosis ; }, abstract = {Colorectal cancer (CRC) ranks second in incidence and third in cancer mortality worldwide. This situation, together with the understanding of the heterogeneity of the disease, has highlighted the need to develop a more individualised approach to its prevention, diagnosis and treatment through personalised medicine. This approach aims to stratify patients according to risk, predict disease progression and determine the most appropriate treatment. It is essential to identify patients who may respond adequately to treatment and those who may be resistant to treatment to avoid unnecessary therapies and minimise adverse side effects. Current research is focused on identifying biomarkers such as specific mutated genes, the type of mutations and molecular profiles critical for the individualisation of CRC diagnosis, prognosis and treatment guidance. In addition, the study of the intestinal microbiota as biomarkers is being incorporated due to the growing scientific evidence supporting its influence on this disease. This article comprehensively addresses the use of current and emerging diagnostic, prognostic and predictive biomarkers in precision medicine against CRC. The effects of host genetics and gut microbiota composition on new approaches to treating this disease are discussed. How the gut microbiota could mitigate the side effects of treatment is reviewed. In addition, strategies to modulate the gut microbiota, such as dietary interventions, antibiotics, and transplantation of faecal microbiota and phages, are discussed to improve CRC prevention and treatment. These findings provide a solid foundation for future research and improving the care of CRC patients.}, }
@article {pmid39396755, year = {2024}, author = {Zhang, Y and Li, P and Chen, B and Zheng, R}, title = {Therapeutic effects of fecal microbial transplantation on alcoholic liver injury in rat models.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {48}, number = {9}, pages = {102478}, doi = {10.1016/j.clinre.2024.102478}, pmid = {39396755}, issn = {2210-741X}, mesh = {Animals ; *Liver Diseases, Alcoholic/therapy ; *Fecal Microbiota Transplantation ; Rats ; *Disease Models, Animal ; *Gastrointestinal Microbiome ; Male ; Rats, Sprague-Dawley ; }, abstract = {OBJECTIVE: Disruption of gut microbiota is closely related to the progression of alcoholic liver disease (ALD). This study aimed to explore the therapeutic effect of fecal microbiota transplantation (FMT) in ALD rats using a combination of microbiological and metabolomic techniques.<br><br>METHODS: Three liver injury rat models were constructed using alcohol, CCL4, and alcohol combined with CCL4, and administered an FMT treatment comprising the fecal microbiota of healthy rats via the gastric route for 12 consecutive weeks. We measured the therapeutic effect of FMT treatment on liver inflammation, intestinal mucosal barrier, and bacterial translocation in ALD rats using 16S rRNA and UPLC-Q/TOF-MS technology to detect the effects of FMT on the intestinal microbiota and metabolic patterns of ALD rats.<br><br>RESULTS: FMT treatment effectively improved liver function, prolonged survival time, improved the intestinal mucosal barrier, reduced bacterial translocation, alleviated liver inflammation, and delayed the progression of liver fibrosis in three types of liver injury models. The microbiome and metabolomic results showed that FMT can effectively improve gut microbiota disorder in ALD rats and improve metabolic patterns by regulating metabolic pathways such as the arachidonic acid and retinol pathways.<br><br>CONCLUSION: FMT treatment could reverse alcohol induced liver injury by improving gut microbiota and metabolic patterns in ALD rats, and oral FMT could be an effective therapeutic approach for ALD.}, }
@article {pmid39396405, year = {2024}, author = {Luo, Z and Yang, L and Zhu, T and Fan, F and Wang, X and Liu, Y and Zhan, H and Luo, D and Guo, J}, title = {Aucubin ameliorates atherosclerosis by modulating tryptophan metabolism and inhibiting endothelial-mesenchymal transitions via gut microbiota regulation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156122}, doi = {10.1016/j.phymed.2024.156122}, pmid = {39396405}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Atherosclerosis/drug therapy/prevention &amp; control ; *Iridoid Glucosides/pharmacology ; *Tryptophan/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Eucommiaceae/chemistry ; Indoleacetic Acids/pharmacology ; Epithelial-Mesenchymal Transition/drug effects ; Mice, Knockout, ApoE ; Fecal Microbiota Transplantation ; Lipid Metabolism/drug effects ; }, abstract = {BACKGROUND: The gut microbiota is believed to influence atherosclerosis (AS), and Aucubin (Au), a natural compound found in the traditional Chinese medicine Eucommia ulmoides Oliver, is being explored as a potential treatment for cardiovascular disease. Yet, the specific impact of Au on AS through the gut microbiota remains unclear.<br><br>PURPOSE: This study aimed to highlight the potential of Au in improving AS by influencing gut microbiota and investigating its potential mechanisms by which it and its metabolites of gut microbiota regulate lipid metabolism, inflammation and endothelial dysfunction.<br><br>METHODS: The impact of Au on AS in ApoE[-/-] mice was examined, followed by a fecal microbiota transplantation experiment to confirm the influence of Au on AS through gut microbiota. Subsequent analysis of fecal and serum samples using 16S rRNA gene sequencing and metabolomics revealed distinct features of gut microbiota and metabolites. Identified metabolites were then utilized in vivo experiments to investigate underlying mechanisms.<br><br>RESULTS: Au treatment effectively reduced dietary-induced dyslipidemia and endothelial dysfunction in a dose-dependent manner in atherosclerotic mice. It also improved vascular plaque accumulation and inflammation, increased aortic valve fibrous cap thickness, and decreased necrotic core and collagen fiber area. Subsequently, we observed a substantial increase in indole-3-acrylic acid (IAA), a microbe-derived metabolite, in cecal contents and serum, along with a significant rise in Lactobacillus abundance responsible for IAA production. Our findings demonstrated that IAA played a crucial role in alleviating AS. Furthermore, we discovered that IAA activated the Aryl hydrocarbon receptor (AhR) and suppressed the TGF-&#x3b2;/Smad pathway, potentially ameliorating endothelial-mesenchymal transitions in atherosclerotic mice.<br><br>CONCLUSION: These findings suggested that Au's anti-atherosclerotic effects were primarily due to elevated Lactobacillus-derived IAA, thereby potentially contributing to alleviating AS.}, }
@article {pmid39395767, year = {2025}, author = {Qi, Z and Liu, J and Xu, Y and Sun, H and Qi, X and Cong, M and Zhang, X and Yan, Y and Liu, T}, title = {Protective effects of phenylethanol glycosides from Cistanche tubulosa against ALD through modulating gut microbiota homeostasis.}, journal = {Journal of ethnopharmacology}, volume = {337}, number = {Pt 3}, pages = {118925}, doi = {10.1016/j.jep.2024.118925}, pmid = {39395767}, issn = {1872-7573}, mesh = {Animals ; *Cistanche/chemistry ; *Glycosides/pharmacology/isolation &amp; purification ; *Gastrointestinal Microbiome/drug effects ; Female ; *Mice, Inbred C57BL ; *Phenylethyl Alcohol/analogs &amp; derivatives/pharmacology/isolation &amp; purification ; *Liver Diseases, Alcoholic/prevention &amp; control/drug therapy ; *Homeostasis/drug effects ; Mice ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Liver/drug effects/metabolism/pathology ; Drugs, Chinese Herbal/pharmacology ; }, abstract = {Cistanche tubulosa (Schenk) Wight, a Chinese herbal medicine (Rou Cong Rong) with Xinjiang characteristics, was recorded in many medical books in ancient China and often used as a tonic medicine. Supported by the traditional Chinese medicine theory of "homology of liver and kidney," C. tubulosa (Schenk) Wight has many clinical applications in tonifying the kidney and protecting the liver. Modern pharmacological studies have also found that the protective effects of phenylethanol glycosides from C. tubulosa (Schenk) Wight (CPhGs) play an important role in ameliorating alcoholic liver injury.<br><br>AIM OF THE STUDY: We aimed to investigate whether CPhGs can enhance the therapeutic outcome of alcoholic liver disease (ALD) by targeting the "gut-liver axis," thus contributing to the knowledge of how Chinese herbs alleviate disease by influencing the gut microbiota.<br><br>MATERIALS AND METHODS: An ALD mouse model was established using the Lieber-DeCarli alcohol liquid diet, and the effects of CPhGs on the intestinal barrier and gut microbiota of ALD mice were investigated in a pseudo-sterile mouse model and fecal microbiota transplantation (FMT) mouse model. We fed female C57BL/6N mice with Lieber-DeCarli ethanol liquid diet, according to the NIAAA model. Animal experiment of long-term, ethanol diet intervention for 6W, and short-term for 11d. The FMT experiments were also performed.<br><br>RESULTS: CPhGs significantly improved ALD manifestations. ALD mice demonstrated significant gut microbiota dysbiosis and significantly abnormal proliferation of Allobaculum compared with the control diet group in long-term NIAAA mouse model (L-Pair). In mice that received the long-term intervention, the improvement in gut barrier function in the CPhGs-treated group was accompanied by a significant decrease in the abundance of Allobaculum and a significant increase in the abundance of Akkermansia. Furthermore, compared with the mouse were gavaged fecal microbiota from the long-term NIAAA mouse donors (FMT-EtOH), the number of goblet cells, abundance of Akkermansia, and the intestinal short-chain fatty acid concentrations were significantly increased in the mouse were gavaged fecal microbiota from high (700&#xa0;mg/kg) doses of CPhGs orally in long-term NIAAA model donors (FMT-EtOH-H). Network analysis and species distribution results demonstrated that Akkermansia and Allobaculum were the genera with the highest abundances in the gut microbiota and that their interaction was related to propionic acid metabolism.<br><br>CONCLUSIONS: The results suggest that CPhGs exert a protective effect against ALD by modulating the abundance and composition of Akkermansia and Allobaculum in the intestine, maintaining the intestinal mucus balance, and safeguarding intestinal barrier integrity.}, }
@article {pmid39395412, year = {2025}, author = {Talwar, C and Davuluri, GVN and Kamal, AHM and Coarfa, C and Han, SJ and Veeraragavan, S and Parsawar, K and Putluri, N and Hoffman, K and Jimenez, P and Biest, S and Kommagani, R}, title = {Identification of distinct stool metabolites in women with endometriosis for non-invasive diagnosis and potential for microbiota-based therapies.}, journal = {Med (New York, N.Y.)}, volume = {6}, number = {2}, pages = {100517}, pmid = {39395412}, issn = {2666-6340}, support = {R01 CA220297/CA/NCI NIH HHS/United States ; R01 HD104813/HD/NICHD NIH HHS/United States ; U54 HG006348/HG/NHGRI NIH HHS/United States ; R01 CA216426/CA/NCI NIH HHS/United States ; P50 HD103555/HD/NICHD NIH HHS/United States ; P30 ES030285/ES/NIEHS NIH HHS/United States ; R01 HD102680/HD/NICHD NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Endometriosis/diagnosis/microbiology/metabolism/therapy ; *Feces/microbiology/chemistry ; Animals ; Mice ; *Gastrointestinal Microbiome ; Metabolomics ; Metabolome ; Indoles/metabolism ; Adult ; Fecal Microbiota Transplantation ; Disease Models, Animal ; }, abstract = {BACKGROUND: Endometriosis, a poorly studied gynecological condition, is characterized by the presence of ectopic endometrial lesions resulting in pelvic pain, inflammation, and infertility. These associated symptoms contribute to a significant burden, often exacerbated by delayed diagnosis. Current diagnostic methods involve invasive procedures, and existing treatments provide no cure.<br><br>METHODS: Microbiome-metabolome signatures in stool samples from individuals with and without endometriosis were determined using unbiased metabolomics and 16S bacteria sequencing. Functional studies for selected microbiota-derived metabolites were conducted in&#xa0;vitro using patient-derived cells and in&#xa0;vivo by employing murine and human xenograft pre-clinical disease models.<br><br>FINDINGS: We discovered a unique bacteria-derived metabolite signature intricately linked to endometriosis. The altered fecal metabolite profile exhibits a strong correlation with that observed in inflammatory bowel disease (IBD), revealing intriguing connections between these two conditions. Notably, we validated 4-hydroxyindole, a gut-bacteria-derived metabolite that is lower in stool samples of endometriosis. Extensive in&#xa0;vivo studies found that 4-hydroxyindole suppressed the initiation and progression of endometriosis-associated inflammation and hyperalgesia in heterologous mouse and in pre-clinical models of the disease.<br><br>CONCLUSIONS: Our findings are the first to provide a distinct stool metabolite signature in women with endometriosis, which could serve as stool-based non-invasive diagnostics. Further, the gut-microbiota-derived 4-hydroxyindole poses as a therapeutic candidate for ameliorating endometriosis.<br><br>FUNDING: This work was funded by the NIH/NICHD grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society to R.K.}, }
@article {pmid39395000, year = {2024}, author = {Sayol-Altarriba, A and Aira, A and Villasante, A and Albarracín, R and Faneca, J and Casals, G and Villanueva-Cañas, JL and Casals-Pascual, C}, title = {Normalization of short-chain fatty acid concentration by bacterial count of stool samples improves discrimination between eubiotic and dysbiotic gut microbiota caused by Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2415488}, pmid = {39395000}, issn = {1949-0984}, mesh = {Humans ; *Fatty Acids, Volatile/metabolism/analysis ; *Feces/microbiology/chemistry ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology ; *Dysbiosis/microbiology ; *Clostridioides difficile/metabolism ; *Bacterial Load ; Male ; Female ; Middle Aged ; Adult ; Aged ; Butyrates/metabolism/analysis ; Bacteria/classification/isolation &amp; purification/metabolism/genetics ; }, abstract = {Short-chain fatty acids (SCFAs) represent a cornerstone of gut health, serving as critical mediators of immune modulation and overall host homeostasis. Patients with dysbiosis caused by Clostridioides difficile infection (CDI) typically exhibit lower SCFAs levels compared to healthy stool donors and, thus, the concentration of SCFAs has been proposed as a proxy marker of a healthy microbiota. However, there is no consistency in the methods used to quantify SCFAs in stool samples and usually, the results are normalized by the weight of the stool samples, which does not address differences in water and fiber content and ignores bacterial counts in the sample (the main component of stool that contributes to the composition of these metabolites in the sample). Here, we show that normalized SCFAs concentrations by the bacterial count improve discrimination between healthy and dysbiotic samples (patients with CDI), particularly when using acetate and propionate levels. After normalization, butyrate is the metabolite that best discriminates eubiotic and dysbiotic samples according to the area under the receiver operating characteristic (ROC) curve (AUC-ROC = 0.860, [95% CI: 0.786-0.934], p < .0001).}, }
@article {pmid39394819, year = {2024}, author = {Dong, L and Luo, P and Zhang, A}, title = {Intestinal microbiota dysbiosis contributes to the liver damage in subchronic arsenic-exposed mice.}, journal = {Acta biochimica et biophysica Sinica}, volume = {56}, number = {12}, pages = {1774-1788}, pmid = {39394819}, issn = {1745-7270}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dysbiosis/chemically induced/microbiology ; *Mice, Inbred C57BL ; *Liver/metabolism/pathology/drug effects ; *Arsenic/toxicity ; Mice ; *Fecal Microbiota Transplantation ; Male ; Chemical and Drug Induced Liver Injury/pathology/metabolism/microbiology/etiology ; }, abstract = {There is an extensive amount of evidence that links changes in the intestinal microbiota structure to the progression and pathophysiology of many liver diseases. However, comprehensive analysis of gut flora dysbiosis in arsenic-induced hepatotoxicity is lacking. Herein, C57BL/6 mice are exposed to arsenic (1, 2, or 4 mg/kg) for 12 weeks, after which fecal microbiota transplantation (FMT) study is conducted to confirm the roles of the intestinal microbiome in pathology. Treatment with arsenic results in pathological and histological changes in the liver, such as inflammatory cell infiltration and decreased levels of TP and CHE but increased levels of ALP, GGT, TBA, AST, and ALT. Arsenic causes an increase in the relative abundance of Escherichia-Shigella, Klebsiella and Blautia, but a decrease in the relative abundance of Muribaculum and Lactobacillus. In arsenic-exposed mice, protein expressions of Occludin, ZO-1, and MUC2 are significantly decreased, but the level of FITC in serum is increased, and FITC fluorescence is extensively dispersed in the intestinal tract. Importantly, FMT experiments show that mice gavaged with stool from arsenic-treated mice exhibit severe inflammatory cell infiltration in liver tissues. Arsenic-manipulated gut microbiota transplantation markedly facilitates gut flora dysbiosis in the recipient mice, including an up-regulation in Escherichia-Shigella and Bacteroides, and a down-regulation in Lactobacillus and Desulfovibrio. In parallel with the intestinal microbiota wreck, protein expressions of Occludin, ZO-1, and MUC2 are decreased. Our findings suggest that subchronic exposure to arsenic can affect the homeostasis of the intestinal microbiota, induce intestinal barrier dysfunction, increase intestinal permeability, and cause damage to liver tissues in mice.}, }
@article {pmid39394659, year = {2024}, author = {Hachem, Y and Djouadi, LN and Raddaoui, A and Boukli-Hacene, F and Boumerdassi, H and Achour, W and Nateche, F}, title = {Phenotypic and molecular characterization of vancomycin resistant enterococci from wild birds: first detection of a plasmid-borne vanC1 in Enterococcus faecalis.}, journal = {Letters in applied microbiology}, volume = {77}, number = {10}, pages = {}, doi = {10.1093/lambio/ovae098}, pmid = {39394659}, issn = {1472-765X}, support = {//DGRSDT/ ; //Ministry of Higher Education and Scientific Research/ ; }, mesh = {Animals ; *Enterococcus faecalis/genetics/drug effects/isolation &amp; purification ; *Birds/microbiology ; *Plasmids/genetics ; *Anti-Bacterial Agents/pharmacology ; *Bacterial Proteins/genetics ; *Animals, Wild/microbiology ; *Feces/microbiology ; *Vancomycin-Resistant Enterococci/genetics/isolation &amp; purification/drug effects ; *Microbial Sensitivity Tests ; Cloaca/microbiology ; Drug Resistance, Multiple, Bacterial/genetics ; Gram-Positive Bacterial Infections/veterinary/microbiology ; Algeria ; Vancomycin/pharmacology ; Virulence Factors/genetics ; Vancomycin Resistance/genetics ; Phenotype ; Bird Diseases/microbiology ; Peptide Synthases ; }, abstract = {Vancomycin-resistant enterococci (VRE) are a public health concern as they lead to therapeutic impasses and play a pivotal role in the dissemination of vancomycin resistance genes. As recent evidence suggests that wildlife can play a role in the dissemination of bacterial resistomes, this study explored the potential role of Algerian wild birds as a reservoir of VRE. A total of 222 cloacal and fecal samples were collected from various wild bird species and screened for VRE using a selective medium. Of the 47 isolated strains, 22 were identified as Enterococcus casseliflavus with the vanC2/C3 gene, 24 as Enterococcus gallinarum (19 carrying vanC1 and five carrying vanC2/C3), and one strain as Enterococcus faecalis with the vanC1 gene. Twenty-four (24) strains were multidrug-resistant with 61.7% resistant to rifampicin, while no resistance to teicoplanin, linezolid, and gentamicin was found. Additionally, 53.20% of the strains exhibited at least one virulence factor. To our knowledge, this study represents the first documentation of the vanC1 gene in E. faecalis isolated from wild birds. Furthermore, this gene was found to be carried by a conjugative plasmid, highlighting its ability to spread among bacterial populations and lead to the emergence of novel resistance phenotypes.}, }
@article {pmid40303777, year = {2023}, author = {De Sabato, L and Ianiro, G and Alborali, GL and Kroneman, A and Grierson, SS and Krumova-Valcheva, GL and Hakze-van der Honing, RW and Johne, R and Kolackova, I and Kozyra, I and Gyurova, E and Pavoni, E and Reisp, K and Sassu, EL and Schilling-Loeffler, K and Smith, RP and Vasickova, P and Żmudzki, J and Rzeżutka, A and Di Bartolo, I}, title = {Molecular Characterization and Phylogenetic Analysis of Hepatitis E Virus (HEV) Strains from Pigs Farmed in Eight European Countries between 2020 and 2022.}, journal = {Transboundary and emerging diseases}, volume = {2023}, number = {}, pages = {2806835}, pmid = {40303777}, issn = {1865-1682}, mesh = {Animals ; *Hepatitis E virus/genetics/isolation &amp; purification/classification ; Swine ; *Hepatitis E/veterinary/virology/epidemiology ; *Swine Diseases/virology/epidemiology ; Phylogeny ; Europe/epidemiology ; Feces/virology ; Genotype ; }, abstract = {In high-income countries, the hepatitis E virus (HEV) is considered an emerging threat causing autochthonous acute hepatitis in humans, with an increased number of reported cases over the last 10 years and related increased burden of chronic hepatitis in immunocompromised and transplant patients. Pigs are the main reservoir of the HEV-3 genotype, which is the most common in Europe, and can be transmitted to humans through the consumption of raw and undercooked pork products. Extensive sequencing revealed the existence of several HEV-3 subtypes in both humans and pigs, confirming a broad heterogeneity of the virus, with some subtypes, such as 3e, 3f, and 3c, which are predominant in Europe. In this study, 291 HEV sequences were obtained from pig feces sampled in more than 74 farms located in Austria, Bulgaria, Czech Republic, Germany, Italy, Poland, the United Kingdom, as well as an unknown number of farms in Netherlands. Of the 99 nonidentical sequences (99/291), 90 were assigned to seven established HEV-3 subtypes: 3a, 3c, 3e, 3f, 3g (here named 3g-like), 3i, and 3l (named 3l-like), already described in Europe, while nine sequences of HEV-3 could not be assigned to any existing subtype (here named 3 [∗]). The 3e subtype was the most common, detected in six out of eight countries, followed by 3f and 3c, which were also present in several countries; 3g-like, 3i, and 3l-like subtypes showed only a limited circulation. The distribution of frequently (3e, 3f, and 3c) and rarely (3g-like, 3i, and 3l-like) detected HEV-3 subtypes in pigs was correlated with their detection rates in human patients in Europe. The results from this study confirm the wide circulation of several HEV-3 strains in European pigs and confirm that sequencing is needed to monitor the different strains and to identify possible zoonotic transmission paths.}, }
@article {pmid39816646, year = {2023}, author = {Karukappadath, RM and Sirbu, D and Zaky, A}, title = {Drug-resistant bacteria in the critically ill: patterns and mechanisms of resistance and potential remedies.}, journal = {Frontiers in antibiotics}, volume = {2}, number = {}, pages = {1145190}, pmid = {39816646}, issn = {2813-2467}, abstract = {Antimicrobial resistance in the intensive care unit is an ongoing global healthcare concern associated with high mortality and morbidity rates and high healthcare costs. Select groups of bacterial pathogens express different mechanisms of antimicrobial resistance. Clinicians face challenges in managing patients with multidrug-resistant bacteria in the form of a limited pool of available antibiotics, slow and potentially inaccurate conventional diagnostic microbial modalities, mimicry of non-infective conditions with infective syndromes, and the confounding of the clinical picture of organ dysfunction associated with sepsis with postoperative surgical complications such as hemorrhage and fluid shifts. Potential remedies for antimicrobial resistance include specific surveillance, adequate and systematic antibiotic stewardship, use of pharmacokinetic and pharmacodynamic techniques of therapy, and antimicrobial monitoring and adequate employment of infection control policies. Novel techniques of combating antimicrobial resistance include the use of aerosolized antibiotics for lung infections, the restoration of gut microflora using fecal transplantation, and orally administered probiotics. Newer antibiotics are urgently needed as part of the armamentarium against multidrug-resistant bacteria. In this review we discuss mechanisms and patterns of microbial resistance in a select group of drug-resistant bacteria, and preventive and remedial measures for combating antibiotic resistance in the critically ill.}, }
@article {pmid39877812, year = {2021}, author = {Zhu, W and Dykstra, K and Zhang, L and Xia, Z}, title = {Gut Microbiome as Potential Therapeutics in Multiple Sclerosis.}, journal = {Current treatment options in neurology}, volume = {23}, number = {11}, pages = {}, pmid = {39877812}, issn = {1092-8480}, support = {R01 NS098023/NS/NINDS NIH HHS/United States ; R01 NS124882/NS/NINDS NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: The gut microbiome is an emerging arena to investigate multiple sclerosis (MS) pathogenesis and potential therapeutics. In this review, we summarize the available data and postulate the feasibilities of potential MS therapeutic approaches that modulate the gut microbiome.<br><br>RECENT FINDINGS: Growing evidence indicates dysbiosis in the gut bacterial ecosystem in MS. Diet and other interventions produce biologically significant changes in the gut bacterial communities and functions, can potentially regulate the immune system, and benefit people with MS. While well-conducted investigations of the therapeutic mechanisms for targeting gut microbiome in animal models and humans remain limited, promising connections between various mechanisms of gut microbiome regulation and beneficial effects on MS outcomes are emerging.<br><br>SUMMARY: To date, studies examining the microbiome-based therapies in MS remain limited in number and follow-up duration. There is a clear need to determine the long-term efficacy and safety of these approaches, and to identify their underlying mechanisms of actions.}, }
@article {pmid39387234, year = {2025}, author = {Benech, N and Cassir, N and Alric, L and Barbut, F and Batista, R and Bleibtreu, A and Briot, T and Davido, B and Galperine, T and Joly, AC and Kapel, N and Melchior, C and Mosca, A and Nebbad, B and Pigneur, B and Schneider, SM and Wasiak, M and Scanzi, J and Sokol, H and , }, title = {Impact of Clinical and Pharmacological Parameters on Faecal Microbiota Transplantation Outcome in Clostridioides difficile Infections: Results of a 5-Year French National Survey.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {61}, number = {1}, pages = {159-167}, pmid = {39387234}, issn = {1365-2036}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/therapy ; France ; Male ; Female ; Retrospective Studies ; Aged ; Middle Aged ; Treatment Outcome ; Recurrence ; Clostridioides difficile ; Adult ; Aged, 80 and over ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Detailed comparative assessment of procedure-related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited.<br><br>AIMS: We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure-related factors associated with FMT success in CDI.<br><br>METHODS: We performed a nationwide retrospective multicentre cohort study. All FMTs performed within The French Faecal Transplant Group for CDI from 2018 to 2022 were included. Clinical data were collected retrospectively from recipient medical files, characteristics of stool transplant preparations were prospectively collected by each Pharmacy involved. Univariate and multivariate analyses were performed using Fisher's test and multiple logistic regression.<br><br>RESULTS: Six hundred fifty-eight FMTs were performed for 617 patients in 17 centres. The overall efficacy of FMT was 84.3% (520/617), with 0.5% of severe adverse events possibly related to FMT (3/658). Forty-seven patients were treated at the first recurrence of CDI with a similar success rate (85.1%). Severe chronic kidney disease (CKD; OR: 2.18, 95%CI [1.20-3.88]), non-severe refractory CDI (OR: 15.35, [1.94-318.2]), the use of &#x2265;&#x2009;80% glycerol (OR: 2.52, [1.11-5.67]), insufficient bowel cleansing (OR: 5.47, [1.57-20.03]) and partial FMT retention (OR: 9.97, [2.62-48.49]) were associated with CDI recurrence within 8&#x2009;weeks.<br><br>CONCLUSIONS: Conditions of transplant manufacturing, bowel cleansing, and a route of delivery tailored to the patient's characteristics are key factors in optimising FMT efficacy. FMT at first recurrence showed high success in real-life practice, whereas it had lower efficacy in severe CDI and non-severe refractory CDI.}, }
@article {pmid39393983, year = {2024}, author = {Hamilton, AM and Krout, IN and White, AC and Sampson, TR}, title = {Microbiome-based therapeutics for Parkinson's disease.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {6}, pages = {e00462}, pmid = {39393983}, issn = {1878-7479}, support = {R01 ES032440/ES/NIEHS NIH HHS/United States ; T32 NS096050/NS/NINDS NIH HHS/United States ; }, mesh = {*Parkinson Disease/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation/methods ; *Probiotics/therapeutic use/administration &amp; dosage ; Animals ; *Prebiotics/administration &amp; dosage ; }, abstract = {Recent experimental and clinical data demonstrate a significant dysregulation of the gut microbiome in individuals with Parkinson's disease (PD). With an immense influence on all aspects of physiology, this dysregulation has potential to directly or indirectly contribute to disease pathology. Experimental models have bridged these associations toward defined contributions, identifying various microbiome-dependent impacts to PD pathology. These studies have laid the foundation for human translation, examining whether certain members of the microbiome and/or whole restoration of the gut microbiome community can provide therapeutic benefit for people living with PD. Here, we review recent and ongoing clinically-focused studies that use microbiome-targeted therapies to limit the severity and progression of PD. Fecal microbiome transplants, prebiotic interventions, and probiotic supplementation are each emerging as viable methodologies to augment the gut microbiome and potentially limit PD symptoms. While still early, the data in the field to date support continued cross-talk between experimental systems and human studies to identify key microbial factors that contribute to PD pathologies.}, }
@article {pmid39393976, year = {2024}, author = {Quera, R and Nuñez, P and von Muhlenbrock, C and Espinoza, R}, title = {Fecal microbiota transplantation through colonoscopy in the treatment of recurrent Clostridioides difficile: Experience at a university center.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {89}, number = {4}, pages = {513-520}, doi = {10.1016/j.rgmxen.2024.03.004}, pmid = {39393976}, issn = {2255-534X}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Female ; Middle Aged ; Male ; *Colonoscopy ; *Clostridium Infections/therapy ; Aged ; *Recurrence ; Adult ; Treatment Outcome ; Clostridioides difficile ; Follow-Up Studies ; Retrospective Studies ; }, abstract = {INTRODUCTION: The majority of cases of Clostridioides difficile infection (CDI) respond to antibiotic treatment. Fecal microbiota transplantation (FMT) has been accepted as an effective treatment in cases of recurrent CDI.<br><br>AIM: Our aim was to describe the clinical results of FMT performed for the treatment of recurrent CDI.<br><br>MATERIAL AND METHODS: The study was conducted on patients with recurrent CDI treated with FMT through colonoscopy, within the time frame of January 2021 and December 2023. Demographic and clinical data were collected, including pre-FMT treatment data, the FMT success rate, and clinical progression during follow-up. Telephone surveys were carried out to evaluate satisfaction.<br><br>RESULTS: Thirteen patients with a mean age of 55 years underwent FMT (including 7 patients above 65 years of age and one pregnant woman). Patients presented with a median of 3 previous episodes of CDI (range 2-4). The median time interval from first episode of CDI to FMT was 4 months (range 3-10). The effectiveness of a single FMT session was 100%. During post-FMT follow-up (median of 11 months, range 3-32), 3 patients have presented with a new CDI episode, and a successful second FMT was performed on 2 of them. No adverse events were registered, and all patients had a positive perception of FMT.<br><br>CONCLUSIONS: In the present study, despite its small size, FMT through colonoscopy was shown to be a safe, effective, and lasting therapy in cases of recurrent CDI, concurring with results from larger studies.}, }
@article {pmid39393822, year = {2024}, author = {Liu, T and Fan, S and Meng, P and Ma, M and Wang, Y and Han, J and Wu, Y and Li, X and Su, X and Lu, C}, title = {Dietary Dihydroquercetin Alleviated Colitis via the Short-Chain Fatty Acids/miR-10a-5p/PI3K-Akt Signaling Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {42}, pages = {23211-23223}, doi = {10.1021/acs.jafc.4c03278}, pmid = {39393822}, issn = {1520-5118}, mesh = {Animals ; *MicroRNAs/genetics/metabolism ; *Quercetin/analogs &amp; derivatives/administration &amp; dosage/metabolism/pharmacology ; *Colitis/drug therapy/metabolism/genetics ; Mice ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; *Gastrointestinal Microbiome/drug effects ; *Fatty Acids, Volatile/metabolism ; Male ; *Signal Transduction/drug effects ; *Phosphatidylinositol 3-Kinases/metabolism/genetics ; *Mice, Inbred C57BL ; Humans ; Bacteria/genetics/classification/isolation &amp; purification/metabolism/drug effects ; }, abstract = {Gut microbiota provides an important insight into clarifying the mechanism of active substances with low bioavailability, but its specific action mechanism varied case by case and remained unclear. Dihydroquercetin (DHQ) is a bioactive flavonoid with low bioavailability, which showed beneficial effects on colitis alleviation and gut microbiota modulation. Herein, we aimed to explore the microbiota-dependent anticolitis mechanism of DHQ in sight of gut microbiota metabolites and their interactions with microRNAs (miRNAs). Dietary supplementation of DHQ alleviated dextran sulfate sodium-induced colitis phenotypes and improved gut microbiota dysbiosis. Fecal microbiota transplantation further revealed that the anticolitis activity of DHQ was mediated by gut microbiota. To clarify how the modulated gut microbiota alleviated colitis in mice, the tandem analyses of the microbiome and targeted metabolome were performed, and altered profiles of metabolite short-chain fatty acids (SCFAs) and bile acids and their producers were observed in DHQ-treated mice. In addition, SCFA treatment showed anticolitis activity compared to that of bile acids, along with the specific inhibition on the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) pathway. Subsequently, the colonic miRNA profile of mice receiving SCFA treatment was sequenced, and a differentially expressed miR-10a-5p was identified. Both prediction analysis and dual-luciferase reporter assay indicated that miR-10a-5p directly bind to the 3'-untranslated regions of gene pik3ca, inhibit the PI3K-Akt pathway activation, and lead to colitis alleviation. Together, we proposed that gut microbiota mediated the anticolitis activity of DHQ through the SCFAs/miR-10a-5p/PI3K-Akt axis, and it provided a novel insight into clarifying the microbiota-dependent mechanism via the interaction between metabolites and miRNAs.}, }
@article {pmid39393557, year = {2025}, author = {Zhou, J and Yang, Q and Wei, W and Huo, J and Wang, W}, title = {Codonopsis pilosula polysaccharide alleviates ulcerative colitis by modulating gut microbiota and SCFA/GPR/NLRP3 pathway.}, journal = {Journal of ethnopharmacology}, volume = {337}, number = {Pt 2}, pages = {118928}, doi = {10.1016/j.jep.2024.118928}, pmid = {39393557}, issn = {1872-7573}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/chemically induced/pathology/metabolism ; *Codonopsis/chemistry ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Fatty Acids, Volatile/metabolism ; *Receptors, G-Protein-Coupled/metabolism ; Male ; Mice ; *Polysaccharides/pharmacology/isolation &amp; purification ; *Dextran Sulfate ; *Mice, Inbred C57BL ; Signal Transduction/drug effects ; Disease Models, Animal ; Colon/drug effects/pathology/metabolism ; Cytokines/metabolism ; }, abstract = {Codonopsis pilosula (Franch.) Nannf. (CP) is a Chinese herb commonly used in traditional Chinese medicine to treat ulcerative colitis (UC). C. pilosula polysaccharide (CPPS) is an important bioactive compound in CP. Polysaccharides are degraded by and interact with the gut microbiota, exerting therapeutic effects. However, the mechanism of action of CPPS in treating UC by regulating gut microbiota is unclear.<br><br>AIM OF THE STUDY: This study aimed to elucidate the therapeutic efficacy of CPPS on UC mice and its mechanism of action.<br><br>MATERIALS AND METHODS: Size-exclusion chromatography with multi-angle laser-light scattering and refractive index analysis was employed to ascertain the molecular weight of CPPS, while its monosaccharide composition was determined using ion chromatography. An experimental colitis mouse model was induced by administering 3% (dextran sulfate sodium) DSS in drinking water for five consecutive days. Three doses of CPPS were administered to evaluate their therapeutic effects on UC. CPPS was administered for seven days, and salicylazosulfapyridine was used as a positive control. Inflammatory cytokine secretion in the colon tissue was measured, and histopathological evaluation was performed on colon sections. Alterations in the abundance of the intestinal microbiota species were also analyzed. We then quantified short-chain fatty acids (SCFAs) in the cecal content and verified the G protein-coupled receptor (GPR)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathways using Western blot. Furthermore, the ameliorative effect of gut microbiota on DSS-induced UC symptoms was verified using the fecal microbiota transplantation (FMT) experiment.<br><br>RESULTS: CPPS comprised of rhamnose, arabinose, galactose, glucose, and galacturonic acid. CPPS significantly alleviated DSS-induced UC. Compared to the DSS group, CPPS treatment significantly increased the ratio of the Firmicutes to the Bacteroidetes and upregulated the abundance of beneficial bacteria such as g__Ligilactobacillus, g_Akkermansia, g_Faecalibaculum, g_Odoribacter. The release of acetic acid and butyric acid were further promoted. CPPS can inhibit NLRP3 activation by binding SCFAs to GPR proteins, thereby reducing intestinal inflammation. FMT confirmed that the gut microbiota in the CPPS-trans group sufficiently mitigated DSS-induced UC symptoms.<br><br>CONCLUSIONS: CPPS ameliorates the symptoms of DSS-induced UC primarily through the gut microbiota modulation and SCFA/GPR/NLRP3 pathways, making it a promising candidate for UC treatment.}, }
@article {pmid39391755, year = {2024}, author = {Fu, Y and Gu, Z and Cao, H and Zuo, C and Huang, Y and Song, Y and Jiang, Y and Wang, F}, title = {The role of the gut microbiota in neurodegenerative diseases targeting metabolism.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1432659}, pmid = {39391755}, issn = {1662-4548}, abstract = {In recent years, the incidence of neurodegenerative diseases (NDs) has gradually increased over the past decades due to the rapid aging of the global population. Traditional research has had difficulty explaining the relationship between its etiology and unhealthy lifestyle and diets. Emerging evidence had proved that the pathogenesis of neurodegenerative diseases may be related to changes of the gut microbiota's composition. Metabolism of gut microbiota has insidious and far-reaching effects on neurodegenerative diseases and provides new directions for disease intervention. Here, we delineated the basic relationship between gut microbiota and neurodegenerative diseases, highlighting the metabolism of gut microbiota in neurodegenerative diseases and also focusing on treatments for NDs based on gut microbiota. Our review may provide novel insights for neurodegeneration and approach a broadly applicable basis for the clinical therapies for neurodegenerative diseases.}, }
@article {pmid39391303, year = {2024}, author = {Karimi, M and Shirsalimi, N and Hashempour, Z and Salehi Omran, H and Sedighi, E and Beigi, F and Mortezazadeh, M}, title = {Safety and efficacy of fecal microbiota transplantation (FMT) as a modern adjuvant therapy in various diseases and disorders: a comprehensive literature review.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1439176}, pmid = {39391303}, issn = {1664-3224}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy ; Animals ; Treatment Outcome ; }, abstract = {The human gastrointestinal (GI) tract microbiome is a complex and all-encompassing ecological system of trillions of microorganisms. It plays a vital role in digestion, disease prevention, and overall health. When this delicate balance is disrupted, it can lead to various health issues. Fecal microbiota transplantation (FMT) is an emerging therapeutic intervention used as an adjuvant therapy for many diseases, particularly those with dysbiosis as their underlying cause. Its goal is to restore this balance by transferring fecal material from healthy donors to the recipients. FMT has an impressive reported cure rate between 80% and 90% and has become a favored treatment for many diseases. While FMT may have generally mild to moderate transient adverse effects, rare severe complications underscore the importance of rigorous donor screening and standardized administration. FMT has enormous potential as a practical therapeutic approach; however, additional research is required to further determine its potential for clinical utilization, as well as its safety and efficiency in different patient populations. This comprehensive literature review offers increased confidence in the safety and effectiveness of FMT for several diseases affecting the intestines and other systems, including diabetes, obesity, inflammatory and autoimmune illness, and other conditions.}, }
@article {pmid39391251, year = {2024}, author = {Zheng, J and Chen, H}, title = {Effects of intratumoral microbiota on tumorigenesis, anti-tumor immunity, and microbe-based cancer therapy.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1429722}, pmid = {39391251}, issn = {2234-943X}, abstract = {Intratumoral microbiota (IM) has emerged as a significant component of the previously thought sterile tumor microenvironment (TME), exerting diverse functions in tumorigenesis and immune modulation. This review outlines the historical background, classification, and diversity of IM, elucidating its pivotal roles in oncogenicity, cancer development, and progression, alongside its influence on anti-tumor immunity. The signaling pathways through which IM impacts tumorigenesis and immunity, including reactive oxygen species (ROS), β-catenin, stimulator of interferon genes (STING), and other pathways [NF-κB, Toll-like receptor (TLR), complement, RhoA/ROCK, PKR-like ER kinase (PERK)], are discussed comprehensively. Furthermore, we briefly introduce the clinical implications of IM, emphasizing its potential as a target for novel cancer therapies, diagnostic biomarkers, and prognostic indicators. Notably, microbe-based therapeutic strategies such as fecal microbiome transplantation (FMT), probiotics regulation, bacteriotherapy, bacteriophage therapy, and oncolytic virotherapy are highlighted. These strategies hold promise for enhancing the efficacy of current cancer treatments and warrant further exploration in clinical settings.}, }
@article {pmid39389400, year = {2024}, author = {Campagnoli, LIM and Marchesi, N and Varesi, A and Morozzi, M and Mascione, L and Ricevuti, G and Esposito, C and Galeotti, N and Pascale, A}, title = {New therapeutic avenues in multiple sclerosis: Is there a place for gut microbiota-based treatments?.}, journal = {Pharmacological research}, volume = {209}, number = {}, pages = {107456}, doi = {10.1016/j.phrs.2024.107456}, pmid = {39389400}, issn = {1096-1186}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Multiple Sclerosis/therapy/microbiology/immunology ; Animals ; Brain-Gut Axis ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Dysbiosis/therapy ; Prebiotics/administration &amp; dosage ; }, abstract = {The bidirectional interaction between the gut and the central nervous system (CNS), the so-called gut microbiota-brain axis, is reported to influence brain functions, thus having a potential impact on the development or the progression of several neurodegenerative disorders. Within this context, it has been documented that multiple sclerosis (MS), an autoimmune inflammatory, demyelinating, and neurodegenerative disease of the CNS, is associated with gastrointestinal symptoms, including constipation, dysphagia, and faecal incontinence. Moreover, some evidence suggests the existence of an altered gut microbiota (GM) composition in MS patients with respect to healthy individuals, as well as the potential influence of GM dysbiosis on typical MS features, including increased intestinal permeability, disruption of blood-brain barrier integrity, chronic inflammation, and altered T cells differentiation. Starting from these assumptions, the possible involvement of GM alteration in MS pathogenesis seems likely, and its restoration could represent a supplemental beneficial strategy against this disabling disease. In this regard, the present review will explore possible preventive approaches (including several dietary interventions, the administration of probiotics, prebiotics, synbiotics, and postbiotics, and the use of faecal microbiota transplantation) to be pursued as prophylaxis or in combination with pharmacological treatments with the aim of re-establishing a proper GM, thus helping to prevent the development of this disease or to manage it by alleviating symptoms or slowing down its progression.}, }
@article {pmid39389184, year = {2025}, author = {S Thomas, A and Lu, Y and Campbell, M and Thompson, JA and Tan, D and Faleck, DM and Wang, Y}, title = {Immune Checkpoint Inhibitor-Induced Colitis.}, journal = {Gastroenterology}, volume = {168}, number = {1}, pages = {21-28}, doi = {10.1053/j.gastro.2024.09.034}, pmid = {39389184}, issn = {1528-0012}, }
@article {pmid39387175, year = {2024}, author = {Zhang, K and Zhang, L and Jian, Y and Tang, X and Han, M and Pu, Z and Zhang, Y and Zhou, P}, title = {Early-Life Milk αS1-Casein Allergy Induces the Activation of Astrocytes in Mice and Leads to Stress Vulnerability in Adulthood.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {42}, pages = {23493-23510}, doi = {10.1021/acs.jafc.4c05425}, pmid = {39387175}, issn = {1520-5118}, mesh = {Animals ; Mice ; *Astrocytes/metabolism/immunology ; *Caseins/immunology ; *Milk Hypersensitivity/immunology ; Male ; Humans ; Female ; Anxiety/immunology ; Gastrointestinal Microbiome ; Milk/chemistry ; Mice, Inbred C57BL ; Depression/immunology/metabolism ; Stress, Psychological/immunology ; Disease Models, Animal ; }, abstract = {In recent years, the incidence of food allergies in children has been increasing annually, significantly affecting the quality of life for patients and their families. It has long been suspected that childhood allergies might potentially lead to behavioral and psychological issues in adulthood, but the specific connection remains unclear. In this study, we established a model of young mice allergic to milk αS1-casein, conducted behavioral tests, and employed transcriptomics, immunohistochemistry, Golgi staining, and fecal microbiota transplantation to explore the link between early life allergies and adult psychological problems. The results showed that early life milk protein allergy significantly increased intestinal epithelial permeability in mice, leading to the translocation of gut microbiota metabolites. This process subsequently activated astrocyte lysosomes via SLC15a3, making astrocytes more susceptible. This susceptibility caused mice with early life milk protein allergy to have more activated astrocytes and excessive dendritic spine phagocytosis (normal group: 5.4 ± 1.26 spines/10 μm, allergy group: 3.2 ± 0.92 spines/10 μm) under acute stress in adulthood, leading to anxiety and depressive behaviors.}, }
@article {pmid39386168, year = {2024}, author = {Hao, L and Yan, Y and Huang, G and Li, H}, title = {From gut to bone: deciphering the impact of gut microbiota on osteoporosis pathogenesis and management.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1416739}, pmid = {39386168}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Osteoporosis/etiology/microbiology ; *Bone Density ; *Bone and Bones/microbiology ; Animals ; Risk Factors ; }, abstract = {Osteoporosis (OP) is characterized by decreased bone mineral density (BMD) and increased fracture risk, poses a significant global health burden. Recent research has shed light on the bidirectional relationship between gut microbiota (GM) and bone health, presenting a novel avenue for understanding OP pathogenesis and developing targeted therapeutic interventions. This review provides a comprehensive overview of the GM-bone axis, exploring the impact of GM on OP development and management. We elucidate established risk factors and pathogenesis of OP, delve into the diversity and functional changes of GM in OP. Furthermore, we examine experimental evidence and clinical observations linking alterations in GM composition or function with variations in BMD and fracture risk. Mechanistic insights into microbial mediators of bone health, such as microbial metabolites and products, are discussed. Therapeutic implications, including GM-targeted interventions and dietary strategies, are also explored. Finally, we identify future research directions and challenges in translating these findings into clinical practice.}, }
@article {pmid39384730, year = {2024}, author = {Liang, Y and Li, Y and Lee, C and Yu, Z and Chen, C and Liang, C}, title = {Ulcerative colitis: molecular insights and intervention therapy.}, journal = {Molecular biomedicine}, volume = {5}, number = {1}, pages = {42}, pmid = {39384730}, issn = {2662-8651}, mesh = {Humans ; *Colitis, Ulcerative/therapy/immunology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain, diarrhea, rectal bleeding, and weight loss. The pathogenesis and treatment of UC remain key areas of research interest. Various factors, including genetic predisposition, immune dysregulation, and alterations in the gut microbiota, are believed to contribute to the pathogenesis of UC. Current treatments for UC include 5-aminosalicylic acids, corticosteroids, immunosuppressants, and biologics. However, study reported that the one-year clinical remission rate is only around 40%. It is necessary to prompt the exploration of new treatment modalities. Biologic therapies, such as anti-TNF-α monoclonal antibody and JAK inhibitor, primarily consist of small molecules targeting specific pathways, effectively inducing and maintaining remission. Given the significant role of the gut microbiota, research into intestinal microecologics, such as probiotics and prebiotics, and fecal microbiota transplantation (FMT) shows promising potential in UC treatment. Additionally, medicinal herbs, such as chili pepper and turmeric, used in complementary therapy have shown promising results in UC management. This article reviews recent findings on the mechanisms of UC, including genetic susceptibility, immune cell dynamics and cytokine regulation, and gut microbiota alterations. It also discusses current applications of biologic therapy, herbal therapy, microecologics, and FMT, along with their prospects and challenges.}, }
@article {pmid39384149, year = {2024}, author = {Wang, H and Cai, Y and Wu, W and Zhang, M and Dai, Y and Wang, Q}, title = {Exploring the role of gut microbiome in autoimmune diseases: A comprehensive review.}, journal = {Autoimmunity reviews}, volume = {23}, number = {12}, pages = {103654}, doi = {10.1016/j.autrev.2024.103654}, pmid = {39384149}, issn = {1873-0183}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Autoimmune Diseases/immunology/microbiology ; Animals ; }, abstract = {As the industrialized society advances, there has been a gradual increase in the prevalence of autoimmune disorders. A probe into the fundamental causes has disclosed several factors in modern society that have an influence on the gut microbiome. These dramatic shifts in the gut microbiome are likely to be one of the reasons for the disarray in the immune system, and the relationship between the immune system and the gut microbiome emerging as a perennial hot topic of research. This review enumerates the findings from sequencing studies of gut microbiota on seven autoimmune diseases (ADs): Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Ankylosing Spondylitis (AS), Systemic Sclerosis (SSc), Sjögren's Syndrome (SjS), Juvenile Idiopathic Arthritis (JIA), and Behçet's Disease (BD). It aims to identify commonalities in changes in the gut microbiome within the autoimmune disease cohort and characteristics specific to each disease. The dysregulation of the gut microbiome involves a disruption of the internal balance and the balance between the external environment and the host. This dysregulation impacts the host's immune system, potentially playing a role in the development of ADs. Damage to the gut epithelial barrier allows potential pathogens to translocate to the mucosal layer, contacting epithelial cells, disrupting tight junctions, and being recognized by antigen-presenting cells, which triggers an immune response. Primed T-cells assist B-cells in producing antibodies against pathogens; if antigen mimicry occurs, an immune response is generated in extraintestinal organs during immune cell circulation, clinically manifesting as ADs. However, current research is limited; advancements in sequencing technology, large-scale cohort studies, and fecal microbiota transplantation (FMT) research are expected to propel this field to new peaks.}, }
@article {pmid39382853, year = {2024}, author = {Khanna, S}, title = {Microbiota restoration for recurrent Clostridioides difficile infection.}, journal = {Panminerva medica}, volume = {66}, number = {4}, pages = {417-426}, doi = {10.23736/S0031-0808.24.05111-5}, pmid = {39382853}, issn = {1827-1898}, mesh = {Humans ; *Clostridium Infections/therapy/microbiology/diagnosis/epidemiology ; *Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile/pathogenicity/drug effects ; Recurrence ; Anti-Bacterial Agents/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Fidaxomicin/therapeutic use ; Treatment Outcome ; Broadly Neutralizing Antibodies ; Antibodies, Monoclonal ; }, abstract = {Since the publication of the recent North American and European guidelines on management of Clostridioides difficile infection (CDI), new evidence describing the epidemiology, testing and treatment of CDI has emerged. Despite all advances in infection control and antibiotic stewardship, the incidence and burden of CDI in the hospitals and the community remains at a stable high. Coupled with the incidence of primary CDI, there is a stable high incidence of recurrent CDI. Testing for primary and recurrent CDI remains a clinical challenge owing to high sensitivity of the PCR (leading to false positives) and somewhat limited sensitivity of EIA for toxin. The pathophysiology of recurrent CDI involves an ongoing disruption of the microbiota owing to the infection and the treatment of CDI employed. Broad spectrum antibiotics such as vancomycin leads to further disruption of microbiota compared to fidaxomicin which has a lower disruption of the microbiota and leads to fewer recurrences. Owing to these data fidaxomicin is considered as the first line antibiotic for recurrent CDI. Intravenous bezlotoxumab is a monoclonal antibody that reduces the risk of recurrence in high-risk patients but does not restore the microbiota. Experimental fecal microbiota transplantation (FMT) has been available for more than a decade. Owing to the success of FMT, two new non-invasive donor dependent Food and Drug Administration (FDA) approved therapies have been available since late 2022. This review summarizes all these conundrums regarding CDI and provides clinical pearls to use in day-to-day practice.}, }
@article {pmid39381749, year = {2024}, author = {Fu, ZP and Ying, YG and Wang, RY and Wang, YQ}, title = {Aged gut microbiota promotes arrhythmia susceptibility via oxidative stress.}, journal = {iScience}, volume = {27}, number = {10}, pages = {110888}, pmid = {39381749}, issn = {2589-0042}, abstract = {Arrhythmias and sudden cardiac death (SCD) impose a significant burden. Their prevalence rises with age and is linked to gut dysbiosis. Our study aimed to determine whether aged gut microbiota affects arrhythmogenesis. Here, we demonstrated that arrhythmia susceptibility in aged mice could be transmitted to young mice using fecal microbiota transplantation (FMT). Mechanistically, increased intestinal reactive oxygen species (ROS) in aged mice reduced ion channel protein expression and promoted arrhythmias. Gut microbiota depletion by an antibiotic cocktail reduced ROS and arrhythmia in aged mice. Interestingly, oxidative stress in heart induced by hydrogen peroxide (H2O2) increased arrhythmia. Moreover, aged gut microbiota could induce oxidative stress in young mice colon by gut microbiota metabolites transplantation. Vitexin could reduce aging and arrhythmia through OLA1-Nrf2 signaling pathway. Overall, our study demonstrated that the gut microbiota of aged mice reduced cardiac ion channel protein expression through systemic oxidative stress, thereby increased the risk of arrhythmias.}, }
@article {pmid39377587, year = {2024}, author = {McMillan, AS and Zhang, G and Dougherty, MK and McGill, SK and Gulati, AS and Baker, ES and Theriot, CM}, title = {Metagenomic, metabolomic, and lipidomic shifts associated with fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {mSphere}, volume = {9}, number = {10}, pages = {e0070624}, pmid = {39377587}, issn = {2379-5042}, support = {RM1 GM145416/GM/NIGMS NIH HHS/United States ; R01 GM141277/GM/NIGMS NIH HHS/United States ; R01 GM141277, RM1 GM145416//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R35GM119438, R35GM149222//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; P42 ES027704/ES/NIEHS NIH HHS/United States ; R35 GM119438/GM/NIGMS NIH HHS/United States ; T32 DK007634/DK/NIDDK NIH HHS/United States ; STAR RD 84003201//Environmental Protection Agency (EPA)/ ; R35 GM149222/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/therapy/microbiology ; *Clostridioides difficile/genetics/metabolism ; *Metabolomics ; *Gastrointestinal Microbiome ; *Feces/microbiology ; *Metagenomics/methods ; *Metabolome ; Male ; Lipidomics ; Female ; Bile Acids and Salts/metabolism ; Recurrence ; Middle Aged ; Aged ; Adult ; Metagenome ; }, abstract = {Recurrent C. difficile infection (rCDI) is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant (FMT). However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we use longitudinal stool samples collected from patients undergoing FMT to evaluate intra-individual changes in the microbiome, metabolome, and lipidome after successful FMTs relative to their baselines pre-FMT. We show changes in the abundance of many lipids, specifically a decrease in acylcarnitines post-FMT, and a shift from conjugated bile acids pre-FMT to deconjugated secondary bile acids post-FMT. These changes correlate with a decrease in Enterobacteriaceae, which encode carnitine metabolism genes, and an increase in Lachnospiraceae, which encode bile acid altering genes such as bile salt hydrolases (BSHs) and the bile acid-inducible (bai) operon, post-FMT. We also show changes in gut microbe-encoded amino acid biosynthesis genes, of which Enterobacteriaceae was the primary contributor to amino acids C. difficile is auxotrophic for. Liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) revealed a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT and generate hypotheses that require further experimental validation. This information is meant to help guide the development of new microbiota-focused therapeutics to treat rCDI.IMPORTANCERecurrent C. difficile infection is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant. However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we show changes in the abundance of many lipids, specifically acylcarnitines and bile acids, in response to FMT. These changes correlate with Enterobacteriaceae pre-FMT, which encodes carnitine metabolism genes, and Lachnospiraceae post-FMT, which encodes bile salt hydrolases and baiA genes. There was also a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT, which we hope will help aid in the development of new microbiota-focused therapeutics to treat rCDI.}, }
@article {pmid39377303, year = {2024}, author = {Berrut, G and Baudron, CR and Paccalin, M and de Wazières, B and Gavazzi, G}, title = {[Clostridioides difficile infections: Update and therapeutic guidelines].}, journal = {Geriatrie et psychologie neuropsychiatrie du vieillissement}, volume = {22}, number = {3}, pages = {316-324}, doi = {10.1684/pnv.2024.1181}, pmid = {39377303}, issn = {2115-7863}, abstract = {Clostridioides difficile infection (CDI) represents a significant challenge due to its increasing incidence, severity, and treatment difficulty. Effective management requires a multifactorial approach that includes preventive strategies, prudent antibiotic use, and adapted therapeutic options. Ongoing research and innovation offer promising prospects for improving ICD management, making vigilance and informed practices essential among healthcare professionals. Two main complications of ICD are pseudomembranous colitis (PMC) and toxic megacolon. PMC involves severe colonic inflammation due to C. difficile toxins, leading to pseudomembrane formation. Diagnosis relies on clinical criteria, microbiological tests, and endoscopy. Toxic Megacolon is characterized by severe colonic dilation and systemic toxicity, requiring immediate medical intervention. ICD diagnosis combines clinical signs and microbiological tests. These tests include toxin tests, GDH antigen detection, PCR for toxin genes, and stool culture. Imaging techniques assess colonic inflammation and complications. Combined diagnostic criteria from the American Gastroenterological Association (AGA) and European guidelines emphasize integrating clinical and laboratory findings for accurate diagnosis. ICD treatment involves stopping the implicated antibiotics and starting specific antimicrobial therapy. Common treatments include mainly fidaxomicin and oral vancomycin. Fecal microbiota transplantation (TMF) is recommended for recurrent cases unresponsive to standard treatments. Bezlotoxumab, an antibody targeting C. difficile toxin B, is used to prevent recurrence in high-risk adults. ICD poses a major challenge due to its increasing incidence, severity, and difficulty in treatment. A multifactorial approach involving rigorous preventive strategies, prudent antibiotic management, and adapted therapeutic options is essential for controlling the infection. Ongoing research and innovations in treatment offer promising prospects for improving patient management. Healthcare professionals must remain vigilant and informed to ensure effective practices in combating this infection and utilizing available resources optimally.}, }
@article {pmid39377231, year = {2024}, author = {Kim, DY and Lee, SY and Lee, JY and Whon, TW and Lee, JY and Jeon, CO and Bae, JW}, title = {Gut microbiome therapy: fecal microbiota transplantation vs live biotherapeutic products.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2412376}, pmid = {39377231}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; Animals ; Clostridium Infections/therapy/microbiology ; Inflammatory Bowel Diseases/therapy/microbiology ; Biological Products/therapeutic use ; Gastrointestinal Diseases/therapy/microbiology ; }, abstract = {The human intestine hosts a complex ecosystem of various microorganisms, collectively known as the gut microbiome, which significantly impacts human health. Disruptions in the gut microbiome are linked to various disorders, including gastrointestinal diseases, such as Clostridioides difficile infection and inflammatory bowel disease, as well as metabolic, neurological, oncologic conditions. Fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) have emerged as prospective therapeutic procedures to restore microbial and metabolic balance in the gut. This review assesses the latest advancements, challenges, and therapeutic efficacy of FMT and LBPs, highlighting the need for standardization, safety, and long-term evaluation to optimize their clinical application.}, }
@article {pmid39375173, year = {2024}, author = {Rognstad, &#xd8;B and Botteri, E and Hoff, G and Bretthauer, M and Gulichsen, E and Frigstad, SO and Holme, &#xd8; and Randel, KR}, title = {Adverse events after colonoscopy in a randomised colorectal cancer screening trial.}, journal = {BMJ open gastroenterology}, volume = {11}, number = {1}, pages = {}, pmid = {39375173}, issn = {2054-4774}, mesh = {Humans ; Male ; Female ; *Colorectal Neoplasms/diagnosis ; *Colonoscopy/adverse effects/statistics &amp; numerical data/methods ; Middle Aged ; *Early Detection of Cancer/methods ; Aged ; Norway/epidemiology ; Cross-Sectional Studies ; Risk Factors ; Sigmoidoscopy/adverse effects/methods/statistics &amp; numerical data ; Occult Blood ; Gastrointestinal Hemorrhage/epidemiology/diagnosis ; Abdominal Pain/etiology ; }, abstract = {OBJECTIVE: Colonoscopy-related adverse events increase the burden of colorectal cancer (CRC) screening. This cross-sectional study evaluates adverse events during and after colonoscopy in a large, randomised CRC screening trial in Norway comparing sigmoidoscopy to immunochemical testing for faecal blood.<br><br>METHODS: We included all individuals who underwent colonoscopy at two screening centres between 2012 and 2020. From medical records, we retrieved data on adverse events during and within 30 days after colonoscopy and classified them according to the American Society for Gastrointestinal Endoscopy lexicon for endoscopic adverse events. Multivariable logistic regression models were fitted to identify risk factors for adverse events.<br><br>RESULTS: Of the 10&#x2009;244 included individuals, 242 (2.4%) had at least one adverse event that was possibly, probably, or definitively related to the colonoscopy. 188 (1.8%) had mild adverse events, 50 (0.49%) had moderate, 3 (0.03%) had severe, and 1 had a fatal adverse event. The most frequent adverse events were lower gastrointestinal bleeding (0.86%), abdominal pain (0.48%), vasovagal reaction (0.39%), postpolypectomy syndrome (0.20%), and perforation (0.08%). 23 (0.22%) individuals had non-gastrointestinal adverse events. Risk factors associated with adverse events were older age, female sex, screening centre, anticoagulant therapy, number of polypectomies, size of lesion removed, presence of proximal lesion, and adenocarcinoma. Adverse event rates per endoscopist ranged from 0% to 4.9%.<br><br>CONCLUSION: Adverse events after colonoscopy of screening positives occurred in about 2 out of 100 procedures. Three-quarters of events were mild. Awareness of risk factors may help endoscopists to mitigate the risk.<br><br>TRIAL REGISTRATION NUMBER: NCT01538550.}, }
@article {pmid39373714, year = {2024}, author = {Chen, Y and Yang, R and Qi, B and Shan, Z}, title = {Peptidoglycan-Chi3l1 interaction shapes gut microbiota in intestinal mucus layer.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {39373714}, issn = {2050-084X}, support = {2019YFA0803100//Ministry of Science and Technology of the People's Republic of China/ ; 32071129//National Natural Science Foundation of China/ ; 32170794//National Natural Science Foundation of China/ ; 202101AT070022//Yunnan Provincial Science and Technology Department/ ; 202201AT070196//Yunnan Provincial Science and Technology Department/ ; C619300A086//Science and Technological Talent Cultivation Plan of Yunnan Province/ ; K264202230211//Science and Technological Talent Cultivation Plan of Yunnan Province/ ; 202302AP370005//Yunnan Provincial Science and Technology Project at Southwest United Graduate School/ ; 2019YFA0802100//Ministry of Science and Technology of the People's Republic of China/ ; 202001AW070006//Yunnan Provincial Science and Technology Department/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Peptidoglycan/metabolism ; *Intestinal Mucosa/metabolism/microbiology ; *Chitinase-3-Like Protein 1/metabolism ; Colitis/microbiology/metabolism/chemically induced ; Mice, Inbred C57BL ; Humans ; Lactobacillus/metabolism ; }, abstract = {The balanced gut microbiota in intestinal mucus layer plays an instrumental role in the health of the host. However, the mechanisms by which the host regulates microbial communities in the mucus layer remain largely unknown. Here, we discovered that the host regulates bacterial colonization in the gut mucus layer by producing a protein called Chitinase 3-like protein 1 (Chi3l1). Intestinal epithelial cells are stimulated by the gut microbiota to express Chi3l1. Once expressed, Chi3l1 is secreted into the mucus layer where it interacts with the gut microbiota, specifically through a component of bacterial cell walls called peptidoglycan. This interaction between Chi3l1 and bacteria is beneficial for the colonization of bacteria in the mucus, particularly for Gram-positive bacteria like Lactobacillus. Moreover, a deficiency of Chi3l1 leads to an imbalance in the gut microbiota, which exacerbates colitis induced by dextran sodium sulfate. By performing fecal microbiota transplantation from Villin-cre mice or replenishing Lactobacillus in IEC[∆Chil1] mice, we were able to restore their colitis to the same level as that of Villin-cre mice. In summary, this study shows a 'scaffold model' for microbiota homeostasis by interaction between intestinal Chi3l1 and bacteria cell wall interaction, and it also highlights that an unbalanced gut microbiota in the intestinal mucus contributes to the development of colitis.}, }
@article {pmid39373173, year = {2025}, author = {Randel, KR and Botteri, E and de Lange, T and Schult, AL and Eskeland, SL and El-Safadi, B and Norvard, ER and Bolstad, N and Bretthauer, M and Hoff, G and Holme, &#xd8;}, title = {Performance of Faecal Immunochemical Testing for Colorectal Cancer Screening at Varying Positivity Thresholds.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {61}, number = {1}, pages = {122-131}, pmid = {39373173}, issn = {1365-2036}, support = {2015038//Helse S&#xf8;r-&#xd8;st RHF/ ; //Norwegian Parliament/ ; }, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Adenoma/diagnosis ; *Colonoscopy/methods ; *Colorectal Neoplasms/diagnosis ; *Early Detection of Cancer/methods ; *Feces/chemistry ; Immunochemistry/methods ; Mass Screening/methods ; Norway ; *Occult Blood ; }, abstract = {BACKGROUND: The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries.<br><br>AIMS: To explore the trade-off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial.<br><br>METHODS: We included first participation in biennial FIT screening for 47,265 individuals aged 50-74&#x2009;years. Individuals with FIT&#x2009;>&#x2009;15&#x2009;&#x3bc;g&#x2009;Hb/g faeces were referred for colonoscopy. We estimated the number of colonoscopies, adverse events, screen-detected CRCs, advanced adenomas and serrated lesions expected at FIT thresholds currently or recently used in other European countries ranging between 20 and 150&#x2009;&#x3bc;g/g.<br><br>RESULTS: At the 15&#x2009;&#x3bc;g/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47&#x2009;&#x3bc;g/g threshold, 1826 (49.3%) individuals would have undergone colonoscopy, and 154 (75.9%) would have been diagnosed with CRC, 702 (62.7%) with advanced adenoma and 128 (50.0%) with advanced serrated lesion compared to the 15&#x2009;&#x3bc;g/g threshold. At 150&#x2009;&#x3bc;g/g, the corresponding figures would have been 838 (22.6%) undergoing colonoscopy, 114 (56.2%) with CRC, 345 (30.8%) advanced adenoma and 54 (21.1%) advanced serrated lesions. The detection rate of stage I CRC was 0.22% at 15&#x2009;&#x3bc;g/g and 0.11% at 150&#x2009;&#x3bc;g/g. Post-colonoscopy bleeding rates were 0.8% and 1.7%, respectively.<br><br>CONCLUSIONS: Increasing the FIT threshold reduces colonoscopy demand, but substantially decreases lesion detection and unfavourably changes CRC stage distribution. The risk of adverse events at colonoscopy increased with FIT threshold, requiring country-specific information on adverse events.<br><br>TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01538550.}, }
@article {pmid39371609, year = {2024}, author = {Yuan, Y and Li, L and Wang, J and Myagmar, BO and Gao, Y and Wang, H and Wang, Z and Zhang, C and Zhang, X}, title = {Gut microbiota-derived acetate promotes long-term recovery through angiogenesis guided by lymphatic ingrowth in older adults with stroke.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1398913}, pmid = {39371609}, issn = {1662-4548}, abstract = {INTRODUCTION: Ischemic stroke is a leading cause of morbidity and mortality in older adults. Therefore, in this study, we sought to understand the interplay between the microbiota, gut, and brain in the context of stroke in older adults.<br><br>OBJECTIVE: To determine whether gut microbiota from younger individuals promotes recovery through angiogenesis in both elderly stroke patients and aged stroke mice, we explored the changes in gut microbiota and the correlation between short-chain fatty acids (SCFAs) and angiogenesis in the aged stroke population. Then, we altered the gut microbiome in aged mice by transplanting microbiota from younger donors before inducing experimental stroke to explore the mechanism by which gut microbiota-derived SCFAs promote angiogenesis.<br><br>METHODS: Part I: We conducted a single-center, double-blind trial to compare gut microbiota diversity and SCFA levels in fecal samples from older stroke patients with those from younger stroke patients. Additionally, we measured levels of vascular endothelial growth factor (VEGF) and VEGFC levels in plasma to assess their correlation with SCFA levels. Part II: We performed fecal microbiota transplantation (FMT) 3 days before inducing ischemic stroke in aged male mice (16-18) via distal middle cerebral artery occlusion (dMCAO). The FMT was conducted using gut microbiomes from either young donors (2-3 months) or aged donors (16-18 months).<br><br>RESULTS: In older stroke patients, gut microbiota diversity was significantly reduced compared to that in younger stroke patients. Furthermore, levels of acetate, a bacterially derived SCFA, were lower and positively correlated with angiogenesis markers (VEGF and VEGF-C). In aged stroke mice, transplantation of young microbiota improved stroke outcomes by promoting angiogenesis, which was facilitated by lymphatic ingrowth into the cortex. This protective effect was linked to gut microbiota-derived acetate, which enhanced lymphangiogenesis by replenishing acetyl coenzyme A.<br><br>CONCLUSIONS: (a) Gut microbiota-derived acetate promotes angiogenesis post-stroke and (b) lymphatic ingrowth into the cerebral cortex was observed in post-dMCAO mice. These findings suggest that selectively promoting SCFA-producing bacteria, particularly acetate-producers, could be a promising therapeutic strategy to reduce functional impairments in older stroke subjects.}, }
@article {pmid39371270, year = {2024}, author = {Dong, H and Li, R and Zhao, N and Dadhania, DM and Suthanthiran, M and Lee, JR and Ling, W}, title = {Antibiotic subclasses differentially perturb the gut microbiota in kidney transplant recipients.}, journal = {Frontiers in transplantation}, volume = {3}, number = {}, pages = {1400067}, pmid = {39371270}, issn = {2813-2440}, support = {R01 GM155734/GM/NIGMS NIH HHS/United States ; }, abstract = {INTRODUCTION: The impact of antibiotics on the gut microbiota in kidney transplant recipients is not well characterized. In this study, we determine the impact of different subclasses of antibiotics on the gut microbiota in a cohort of 168 kidney transplant recipients.<br><br>METHODS: Gut microbiome profiling was performed on 510 fecal specimens using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We classified fecal specimens by antibiotic exposure into 5 categories: Beta-lactam, Fluoroquinolone (FQ), Beta-lactam &amp; FQ Group, Other Antibiotics, and No Antibiotic (No Abx). Mixed-effects regression models were utilized to identify changes in microbial diversity and in the centered log-ratio (CLR) transformed abundance of genera while adjusting for important covariates.<br><br>RESULTS: Antibiotic administration was associated with a significant decrease in the Shannon alpha diversity index, a decreased abundance of 11 taxa including Eubacterium and Ruminococcus, and an increased abundance of 16 taxa including Enterococcus and Staphylococcus. Exposure to Beta-lactam antibiotics was associated with an increased abundance of 10 taxa including Enterococcus and a decreased abundance of 5 taxa including Eubacterium while exposure to FQ antibiotics was associated with an increased abundance of 3 taxa and a decreased abundance of 4 taxa including Ruminococcus.<br><br>CONCLUSIONS: Beta-lactam antibiotics and FQ antibiotics have a profound impact on the gut microbiota in kidney transplant recipients. Given the link of the gut microbiota to infectious complications, antibiotic associated changes in the microbiota may lead to an increased risk for further infections.}, }
@article {pmid39371172, year = {2024}, author = {Akagbosu, CO and McCauley, KE and Namasivayam, S and Romero-Soto, HN and O'Brien, W and Bacorn, M and Bohrnsen, E and Schwarz, B and Mistry, S and Burns, AS and Perez-Chaparro, PJ and Chen, Q and LaPoint, P and Patel, A and Krausfeldt, LE and Subramanian, P and Sellers, BA and Cheung, F and Apps, R and Douagi, I and Levy, S and Nadler, EP and Hourigan, SK}, title = {Gut microbiome shifts in adolescents after sleeve gastrectomy with increased oral-associated taxa and pro-inflammatory potential.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39371172}, support = {R25 DK096944/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown.<br><br>OBJECTIVES: 1) To comprehensively examine gut microbiome and metabolome changes after laparoscopic vertical sleeve gastrectomy (VSG) in adolescents and 2) to assess whether the microbiome/metabolome changes observed with VSG influence phenotype using germ-free murine models.<br><br>DESIGN: 1) A longitudinal observational study in adolescents undergoing VSG with serial stool samples undergoing shotgun metagenomic microbiome sequencing and metabolomics (polar metabolites, bile acids and short chain fatty acids) and 2) a human-to-mouse fecal transplant study.<br><br>RESULTS: We show adolescents exhibit significant gut microbiome and metabolome shifts several months after VSG, with increased alpha diversity and notably with enrichment of oral-associated taxa. To assess causality of the microbiome/metabolome changes in phenotype, pre-VSG and post-VSG stool was transplanted into germ-free mice. Post-VSG stool was not associated with any beneficial outcomes such as adiposity reduction compared pre-VSG stool. However, post-VSG stool exhibited an inflammatory phenotype with increased intestinal Th17 and decreased regulatory T cells. Concomitantly, we found elevated fecal calprotectin and an enrichment of proinflammatory pathways in a subset of adolescents post-VSG.<br><br>CONCLUSION: We show that in some adolescents, microbiome changes post-VSG may have inflammatory potential, which may be of importance considering the increased incidence of inflammatory bowel disease post-VSG.}, }
@article {pmid39370012, year = {2025}, author = {Wang, J and Shen, Y and Li, L and Li, L and Zhang, J and Li, M and Qiu, F}, title = {Lycopene attenuates D-galactose-induced memory and behavioral deficits by mediating microbiota-SCFAs-gut-brain axis balance in female CD-1 mice.}, journal = {The Journal of nutritional biochemistry}, volume = {135}, number = {}, pages = {109777}, doi = {10.1016/j.jnutbio.2024.109777}, pmid = {39370012}, issn = {1873-4847}, mesh = {Animals ; *Galactose ; *Gastrointestinal Microbiome/drug effects ; *Lycopene/pharmacology ; Mice ; Female ; *Brain-Gut Axis/drug effects ; *Fatty Acids, Volatile/metabolism ; *Memory Disorders ; Fecal Microbiota Transplantation ; Dysbiosis ; Behavior, Animal/drug effects ; Brain/metabolism ; Hippocampus/metabolism/drug effects ; Aging ; }, abstract = {Aging impairs cognitive function, whereas nutritional intervention can delay aging and age-related diseases. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, the effects of LYC on memory and behavioral deficits induced by D-galactose (D-gal) treatment and the relative contribution of LYC-derived gut microbiota in these process were investigated. Results demonstrated that LYC showed effective protection on D-gal induced cognitive deficit and neuronal damage. Moreover, LYC treatment has beneficial effects on gut barrier damage, microbiota dysbiosis and levels of SCFAs in D-gal-induced subacute aging mice. Next, fecal microbiota transplantation (FMT) experiment was performed and increased SCFAs were observed in mice received stools from D-gal+LYC group when compared with D-gal-FMT group. Thus, we added SCFAs treatment served as a control group in order to evaluated whether the alterations of gut-brain axis could be attributed to LYC-reshaped gut microbiota and SCFAs. Results showed that recipient mice received SCFAs and stools from D-gal+LYC group have similar beneficial effects in improving gut and brain function, demonstrated as: improved intestinal health via elevating antioxidant enzymes contents, increasing the expressions of tight junctions proteins and protecting gut barrier, enhanced mice working memory capacity via alleviating hippocampal neurons impairment, improving synaptic function and enhancing mitochondrial function in the intestinal pseudo-aseptic mice. In conclusion, our results demonstrated that LYC-derived microbiome played a pivotal role in the regulation of cognitive functions during aging and enhanced SCFAs formation might be an important signaling molecule connecting gut microbiome and brain.}, }
@article {pmid39366468, year = {2025}, author = {Allegretti, JR and Kelly, CR and Louie, T and Fischer, M and Hota, S and Misra, B and Van Hise, NW and Yen, E and Bullock, JS and Silverman, M and Davis, I and McGill, SK and Pardi, DS and Orenstein, R and Grinspan, A and El-Nachef, N and Feuerstadt, P and Borody, TJ and Khanna, S and Budree, S and Kassam, Z}, title = {Safety and Tolerability of CP101, a Full-Spectrum, Oral Microbiome Therapeutic for the Prevention of Recurrent Clostridioides difficile Infection: A Phase 2 Randomized Controlled Trial.}, journal = {Gastroenterology}, volume = {168}, number = {2}, pages = {357-366.e3}, doi = {10.1053/j.gastro.2024.09.030}, pmid = {39366468}, issn = {1528-0012}, mesh = {Humans ; Male ; Female ; *Clostridium Infections/prevention &amp; control/microbiology/diagnosis/therapy ; Middle Aged ; Double-Blind Method ; Aged ; *Clostridioides difficile/isolation &amp; purification ; Administration, Oral ; Treatment Outcome ; Adult ; *Secondary Prevention/methods ; *Gastrointestinal Microbiome ; Anti-Bacterial Agents/therapeutic use ; Recurrence ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND &amp; AIMS: Recurrent Clostridioides difficile infections (CDIs) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full-spectrum, oral microbiome therapeutic is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population.<br><br>METHODS: We conducted a multicenter, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by polymerase chain reaction or toxin enzyme immunoassay for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (&#x223c;6&#xa0;&#xd7; 10[11] colony-forming units of lyophilized microbial cells) or placebo after standard-of-care antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through week 8. Safety, efficacy, and microbiome endpoints were evaluated through weeks 8 and&#xa0;24.<br><br>RESULTS: A total of 198 participants were analyzed: CP101 (n&#xa0;= 102) and placebo (n&#xa0;= 96). Overall, 27.5% had a first recurrence, and 62.7% were diagnosed by polymerase chain reaction-based testing. The proportion without CDI recurrence through week 8 was significantly higher in the CP101 group compared to the placebo group (74.5% [76 of 102] vs 61.5% [59 of 96], respectively; P&#xa0;=&#xa0;.0488), with durable efficacy observed through week 24 (73.5% [75 of 102] vs 59.4% [57 of 96], respectively; P&#xa0;=&#xa0;.0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to the placebo group. The incidence of adverse events was similar between the 2 groups.<br><br>CONCLUSIONS: CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. (ClinicalTrials.gov, Number NCT03110133).}, }
@article {pmid39364128, year = {2024}, author = {Guo, J and Yang, L}, title = {Regulation effect of the intestinal flora and intervention strategies targeting the intestinal flora in alleviation of pulmonary fibrosis development.}, journal = {Bioscience of microbiota, food and health}, volume = {43}, number = {4}, pages = {293-299}, pmid = {39364128}, issn = {2186-6953}, abstract = {Pulmonary fibrosis is an end-stage respiratory disease characterized by fibroblast proliferation and accumulation of extracellular matrix and collagen, which is accompanied by inflammatory damage. The disease is mainly based on pulmonary dysfunction and respiratory failure, the incidence of it is increasing year by year, and the current treatment methods for it are limited. In recent years, it has been found that gut microbes play a crucial role in the pathogenesis and development of pulmonary fibrosis. The microecological disturbance caused by changes in the composition of the intestinal flora can affect the course of pulmonary fibrosis. The regulatory network or information exchange system for gut-lung crosstalk is called the "gut-lung axis". This review focuses on the frontier research on entero-pulmonary regulation in pulmonary fibrosis and on intervention strategies for changing the gut microbiota to improve pulmonary fibrosis, including fecal microbiota transplantation, traditional Chinese medicine interventions, and supplementation with probiotics. In addition, the present problems in this field are also raised in order to provide strong theoretical and strategic support for the future exploration of regulatory mechanisms and therapeutic drug development. This paper reviews the interaction of the intestinal flora with pulmonary fibrosis, introduces the research progress for improving pulmonary fibrosis through interventions targeted at the intestinal flora, and provides new ideas for the treatment of pulmonary fibrosis.}, }
@article {pmid39364121, year = {2024}, author = {Mao, Z and Zhang, J and Guo, L and Wang, X and Zhu, Z and Miao, M}, title = {Therapeutic approaches targeting the gut microbiota in ischemic stroke: current advances and future directions.}, journal = {Bioscience of microbiota, food and health}, volume = {43}, number = {4}, pages = {321-328}, pmid = {39364121}, issn = {2186-6953}, abstract = {Ischemic stroke (IS) is the predominant form of stroke pathology, and its clinical management remains constrained by therapeutic time frame. The gut microbiota (GM), comprising a multitude of bacterial and archaeal cells, surpasses the human cell count by approximately tenfold and significantly contributes to the human organism's growth, development, and overall well-being. The microbiota-gut-brain axis (MGBA) in recent years has established a strong association between gut microbes and the brain, demonstrating their intricate involvement in the progression of IS. The regulation of IS by the GM, encompassing changes in composition, abundance, and distribution, is multifaceted, involving neurological, endocrine, immunological, and metabolic mechanisms. This comprehensive understanding offers novel insights into the therapeutic approaches for IS. The objective of this paper is to examine the mechanisms of interaction between the GM and IS in recent years, assess the therapeutic effects of the GM on IS through various interventions, such as dietary modifications, probiotics, fecal microbiota transplantation, and antibiotics, and offer insights into the potential clinical application of the GM in stroke treatment.}, }
@article {pmid39362719, year = {2024}, author = {Morgan, TR}, title = {Emerging Pharmacologic Treatments for Alcohol-Associated Hepatitis: Current Status and Future Landscape.}, journal = {Clinics in liver disease}, volume = {28}, number = {4}, pages = {747-760}, doi = {10.1016/j.cld.2024.06.014}, pmid = {39362719}, issn = {1557-8224}, mesh = {Humans ; *Hepatitis, Alcoholic/drug therapy/therapy ; Antioxidants/therapeutic use ; Interleukin-22 ; Acetylcysteine/therapeutic use ; Fecal Microbiota Transplantation ; Granulocyte Colony-Stimulating Factor/therapeutic use ; }, abstract = {Several treatments have shown efficacy in preliminary alcohol-associated hepatitis trials. Interleukin-22 improved Model of End-stage Liver Disease score and aminotransferases in a phase II trial. The endogenous cholesterol derivative, larsucosterol, improved outcomes in a multi-center United States or European phase II trial. The antioxidants N-acetylcysteine and metadoxine improved survival in large trials. Trials from India report improved survival with granulocyte-colony stimulating factor, as well as improved outcome among patients receiving fecal microbiota transfer. Translational studies suggest that phage treatment of cytolytic Enterococcus faecalis may reduce liver injury.}, }
@article {pmid39362714, year = {2024}, author = {Yang, Y and Schnabl, B}, title = {Gut Bacteria in Alcohol-Associated Liver Disease.}, journal = {Clinics in liver disease}, volume = {28}, number = {4}, pages = {663-679}, pmid = {39362714}, issn = {1557-8224}, support = {R01 AA020703/AA/NIAAA NIH HHS/United States ; I01 BX004594/BX/BLRD VA/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; U01 AA026939/AA/NIAAA NIH HHS/United States ; }, mesh = {*Liver Diseases, Alcoholic/microbiology/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Dysbiosis ; Liver Function Tests ; }, abstract = {Alcohol-associated liver disease (ALD) poses a significant global public health challenge, with high patient mortality rates and economic burden. The gut microbiome plays an important role in the onset and progression of alcohol-associated liver disease. Excessive alcohol consumption disrupts the intestinal barrier, facilitating the entry of harmful microbes and their products into the liver, exacerbating liver damage. Dysbiosis, marked by imbalance in gut bacteria, correlates with ALD severity. Promising microbiota-centered therapies include probiotics, phages, and fecal microbiota transplantation. Clinical trials demonstrate the potential of these interventions to improve liver function and patient outcomes, offering a new frontier in ALD treatment.}, }
@article {pmid39362281, year = {2025}, author = {Headley, SA and Chapman, DJ and Germain, MJ and Evans, EE and Madsen, KL and Miele, EM and Kirton, K and Loseke, J and Cornelius, A and Martin, B and Nindl, B and Park, H and Vaziri, ND and Ikizler, TA}, title = {Effects of High Amylose-Resistant Starch on Gut Microbiota and Uremic Toxin Levels in Patients With Stage-G3a-G4 Chronic Kidney Disease: A Randomized Trial.}, journal = {Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation}, volume = {35}, number = {2}, pages = {248-258}, doi = {10.1053/j.jrn.2024.09.005}, pmid = {39362281}, issn = {1532-8503}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Female ; Male ; *Renal Insufficiency, Chronic/blood/microbiology ; Middle Aged ; Double-Blind Method ; *Uremic Toxins/blood ; Cresols/blood ; *Amylose/administration &amp; dosage ; Aged ; Indican/blood ; Sulfuric Acid Esters/blood ; *Resistant Starch ; Dietary Supplements ; Biomarkers/blood ; Feces/microbiology ; Oxidative Stress/drug effects ; *Starch/administration &amp; dosage/pharmacology ; Adult ; }, abstract = {OBJECTIVE: This study was designed to determine the effect of 16 weeks of supplementation with Hi-maize 260 resistant starch (RS) on the gut microbiota, uremic toxins (indoxyl sulfate and p-cresyl sulfate [PCS]), markers of inflammation, and oxidative stress along with vascular function in patients with stage G3a-G4 chronic kidney disease (CKD).<br><br>DESIGN AND METHODS: This was a double-blind, placebo-controlled, parallel-arm, randomized controlled trial. Sixty-eight patients with stage-G3a-G4 CKD were randomized to either RS with usual care or placebo and usual care. Patients attended four testing sessions as follows: two baseline (BL) visits and follow-up visits at 8 and 16&#xa0;weeks. Fasting blood samples, resting brachial and central blood pressures, along with arterial stiffness, were collected at visits (1 or 2) and weeks 8 and 16. A stool sample was collected for analysis of microbial composition at BL and week 16. Patients were randomized after the BL visits.<br><br>RESULTS: Patients receiving the RS had a reduction in PCS at week 16. This reduction was associated with a decrease in microbial &#x3b1;-diversity between BL and week 16 (Chao1 P&#xa0;=&#xa0;.014, Shannon P&#xa0;=&#xa0;.017, phylogenetic diversity P&#xa0;=&#xa0;.046, and Simpson P&#xa0;=&#xa0;.017) as well as increases in Subdoligranulum (P&#xa0;=&#xa0;.03) and Oscillospiraceae Unclassified Clostridiales Group 002 (P&#xa0;=&#xa0;.02) and decreases in Bacteroides (P&#xa0;=&#xa0;.009).There were no changes in microbial beta diversity and other biomarkers or markers of vascular function following the 16-week period.<br><br>CONCLUSION: Sixteen weeks of supplementation of RS in patients with stage-G3a-G4 CKD led to changes in microbial composition that were associated with a significant reduction in PCS.}, }
@article {pmid39360770, year = {2024}, author = {Verma, N and Vinod, AP and Singal, AK}, title = {The pharmacological management of alcohol-related cirrhosis: what's new?.}, journal = {Expert opinion on pharmacotherapy}, volume = {25}, number = {14}, pages = {1923-1941}, doi = {10.1080/14656566.2024.2409941}, pmid = {39360770}, issn = {1744-7666}, mesh = {Humans ; *Alcoholism/complications/drug therapy ; *Liver Transplantation ; *Liver Cirrhosis, Alcoholic/drug therapy ; Animals ; Disease Progression ; Hepatitis, Alcoholic/drug therapy/therapy ; Precision Medicine ; }, abstract = {INTRODUCTION: Alcohol use disorder (AUD) is present in the majority of patients with alcohol-associated liver disease (ALD), which leads to about 50% of cirrhosis-related hospitalizations and over 25% of deaths worldwide. Patients with ALD often present at an advanced stage, like cirrhosis with its complications and alcohol-associated hepatitis (AH), which has high short-term mortality. Current treatments are limited, with the limited benefit of glucocorticoids only in the short-term among patients with AH, highlighting an urgent need for novel therapies.<br><br>AREAS COVERED: This review applies the PIRO (Predisposition, Injury, Response, Organ dysfunction) concept to ALD, understanding an ongoing process of liver damage, and opportunities to address and halt the progression. We also highlight the significance of treating AUD to improve long-term outcomes in ALD.<br><br>EXPERT OPINION: Personalized therapies targeting specific genetic profiles and multiple pathogenic pathways are crucial in managing ALD. Emerging therapies like gut-liver-brain axis modulators like fecal microbiota transplant and probiotics, interleukin-22, granulocyte-colony stimulating factor (G-CSF) and stem cells, epigenetic regulators of inflammation and regeneration are encouraging with the potential of efficacy in patients with ALD. Liver transplantation (LT) is a definitive therapy for advanced cirrhosis with increasing impetus on early LT select patients with active alcohol use.}, }
@article {pmid39360586, year = {2024}, author = {Cibulková, I and Řehořová, V and Wilhelm, M and Soukupová, H and Hajer, J and Duška, F and Daňková, H and Cahová, M}, title = {Evaluating Bacterial Viability in Faecal Microbiota Transplantation: A Comparative Analysis of In Vitro Cultivation and Membrane Integrity Methods.}, journal = {Journal of clinical laboratory analysis}, volume = {38}, number = {19-20}, pages = {e25105}, pmid = {39360586}, issn = {1098-2825}, support = {IN 00023001//Institute for Clinical and Experimental medicine - IKEM/ ; //Institutional Support of FNKV University Hospital/ ; VAT No 0907206//Donatio Intensivistam Endowement fund/ ; //Cooperation Intensive Care Medicine Programme of Charles University/ ; }, mesh = {Humans ; *Microbial Viability ; *Feces/microbiology ; Animals ; *Fecal Microbiota Transplantation/methods ; *Flow Cytometry/methods ; Mice ; Bacteria/isolation &amp; purification ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a developing therapy for disorders related to gut dysbiosis. Despite its growing application, standardised protocols for FMT filtrate preparation and quality assessment remain undeveloped. The viability of bacteria in the filtrate is crucial for FMT's efficacy and for validating protocol execution. We compared two methods-in vitro cultivation and membrane integrity assessment-for their accuracy, reproducibility and clinical applicability in measuring bacterial viability in frozen FMT stool filtrate.<br><br>METHODS: Bacterial viability in stool filtrate was evaluated using (i) membrane integrity through fluorescent DNA staining with SYTO9 and propidium iodide, followed by flow cytometry and (ii) culturable bacteria counts (colony-forming units, CFU) under aerobic or anaerobic conditions.<br><br>RESULTS: Using different types of samples (pure bacterial culture, stool of germ-free and conventionally bred mice, native and heat-treated human stool), we refined the bacterial DNA staining protocol integrated with flow cytometry for assessment of bacterial viability in frozen human stool samples. Both the membrane integrity-based and cultivation-based methods exhibited significant variability in bacterial viability across different FMT filtrates, without correlation. The cultivation-based method showed a mean coefficient of variance of 30.3%, ranging from 7.4% to 60.1%. Conversely, the membrane integrity approach yielded more reproducible results, with a mean coefficient of variance for viable cells of 6.4% ranging from 0.2% to 18.2%.<br><br>CONCLUSION: Bacterial viability assessment in stool filtrate using the membrane integrity method offers robust and precise data, making it a suitable option for faecal material evaluation in FMT. In contrast, the cultivation-dependent methods produce inconsistent outcomes.}, }
@article {pmid39360560, year = {2024}, author = {Arzamendi, MJ and Habibyan, YB and Defaye, M and Shute, A and Baggio, CH and Chan, R and Ohland, C and Bihan, DG and Lewis, IA and Sharkey, KA and McCoy, KD and Altier, C and Geuking, MB and Nasser, Y}, title = {Sex-specific post-inflammatory dysbiosis mediates chronic visceral pain in colitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2409207}, pmid = {39360560}, issn = {1949-0984}, mesh = {Male ; Female ; Animals ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; *Visceral Pain/microbiology/physiopathology/metabolism ; *Colitis/microbiology ; Mice ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Sex Factors ; Bacteria/classification/isolation &amp; purification/genetics/metabolism ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Dextran Sulfate ; Disease Models, Animal ; Fatty Acids, Volatile/metabolism/analysis ; Chronic Pain/microbiology/physiopathology ; Inflammation/microbiology ; Hyperalgesia/microbiology ; }, abstract = {BACKGROUND: Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. Visceral pain and the microbiome exhibit sex-dependent interactions, while visceral pain in IBD shows a sex bias. Our aim was to evaluate whether post-inflammatory microbial perturbations contribute to visceral hypersensitivity in a sex-dependent manner.<br><br>METHODS: Males, cycling females, ovariectomized, and sham-operated females were given dextran sodium sulfate to induce colitis and allowed to recover. Germ-free recipients received sex-appropriate and cross-sex fecal microbial transplants (FMT) from post-inflammatory donor mice. Visceral sensitivity was assessed by recording visceromotor responses to colorectal distention. The composition of the microbiota was evaluated via 16S rRNA gene V4 amplicon sequencing, while the metabolome was assessed using targeted (short chain fatty acids - SCFA) and semi-targeted mass spectrometry.<br><br>RESULTS: Post-inflammatory cycling females developed visceral hyperalgesia when compared to males. This effect was reversed by ovariectomy. Both post-inflammatory males and females exhibited increased SCFA-producing species, but only males had elevated fecal SCFA content. FMT from post-inflammatory females transferred visceral hyperalgesia to both males and females, while FMT from post-inflammatory males could only transfer visceral hyperalgesia to males.<br><br>CONCLUSIONS: Female sex, hormonal status as well as the gut microbiota play a role in pain modulation. Our data highlight the importance of considering biological sex in the evaluation of visceral pain.}, }
@article {pmid39358432, year = {2024}, author = {Zhi, W and Li, A and Wang, Q and Yuan, X and Qing, J and Zhang, C and Wang, Y and Li, Y}, title = {Safety and efficacy assessment of fecal microbiota transplantation as an adjunctive treatment for IgA nephropathy: an exploratory clinical trial.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {22935}, pmid = {39358432}, issn = {2045-2322}, support = {82170716//National Science Foundation of China/ ; }, mesh = {Humans ; *Glomerulonephritis, IGA/therapy ; Male ; Female ; Adult ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Gastrointestinal Microbiome ; Middle Aged ; Treatment Outcome ; Cytokines/blood/metabolism ; }, abstract = {To assess the safety and efficacy of fecal microbiota transplantation (FMT) as an adjunctive therapeutic intervention for IgA nephropathy (IgAN). Fifteen patients with IgA nephropathy were recruited based on inclusion and exclusion criteria and underwent FMT using enteric microbial capsules. Clinical indicators, intestinal microbiota and metabolomic profiles, as well as changes in serum immune cells and cytokines, were monitored before and after FMT. No severe adverse reactions were observed in the subjects. After FMT, there was a reduction in the 24-h urinary protein quantification in subjects. The relative abundances of Phocaeicola_vulgatus, Bacteroides_uniformis, Prevotella_copri, Phocaeicola_dorei, Bacteroides_ovatus, Bacteroides_xylanisolvens, Parabacteroides _distasonis, Bifidobacterium_pseudocatenulatum, Bacteroides_sp._HF-162, and Bifidobacterium_longum changed after FMT. In terms of intestinal metabolites, the levels of acylcarnitine18:0 (ACar.18:0), cotinine, N-arachidonoyl-L-serine, phosphatidylcholine (PC. (18:3e/22:6)), serotonin, and fumagillin showed significant changes. Flow cytometry analysis showed the absolute count of plasma B cells decreased in subjects, and this change correlated with alterations in the intestinal microbiota and metabolites. This study preliminarily evaluates the safety and efficacy of FMT in patients with IgAN. No significant adverse reactions were observed, and the administration of FMT alongside ACEI/ARB therapy was effective in reducing urinary protein levels in patients with IgAN, a process that may be associated with B-cell immunity.}, }
@article {pmid39358252, year = {2024}, author = {Tanigawa, H and Kohara, K and Onizuka, M and Otsuka, A and Suzuki, Y and Hirohara, M}, title = {[Survey of Preventing Exposure Regarding Sweat in Patients Receiving Antineoplastic Agents at Base Hospitals for Promoting Hematopoietic Stem Cell].}, journal = {Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, volume = {144}, number = {10}, pages = {957-962}, doi = {10.1248/yakushi.24-00098}, pmid = {39358252}, issn = {1347-5231}, mesh = {Humans ; *Antineoplastic Agents/adverse effects ; *Occupational Exposure/prevention &amp; control ; *Hematopoietic Stem Cell Transplantation ; Surveys and Questionnaires ; *Sweat/chemistry ; Personal Protective Equipment ; Gloves, Protective ; Guideline Adherence ; Clothing ; Practice Guidelines as Topic ; }, abstract = {This survey aimed to reveal the actual preventing exposure for handling of clothing and sweat of patients treated with anticancer drugs, following the publication of "Guideline for Preventing Occupational Exposure in Cancer Chemotherapy Drugs, 2019 Edition" (Guideline 2019). A survey was conducted among nurses working at 95 hematopoietic stem cell transplantation promotion base hospitals from September 1, 2023 to October 31, 2023. The response rate was 84.2% (80 facilities). Of the respondents, 45% wore gloves when touching patients' skin to administer anticancer drugs. Almost the nurses identified "urine" and "feces" as fluids on contaminated linen, while 14.1% also identified "sweat." For new staff, the results for preventing exposure education on "if touching the patients' skin" and "if handling clothing and linen" were 23.8% and 34.9%, respectively. This survey shows that nurses may not be following the Guideline 2019 for use of personal protective equipment and handling of clothes. Medical institutions handling anticancer drugs need to educate their staff for preventing occupational exposure.}, }
@article {pmid39353099, year = {2024}, author = {Loman, BR and Alzoubi, Z and Lynch, AJ and Jaggers, RM and Jordan, K and Grant, CV and Rogers, LK and Pyter, LM and Bailey, MT}, title = {Paclitaxel chemotherapy disrupts microbiota-enterohepatic bile acid metabolism in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2410475}, pmid = {39353099}, issn = {1949-0984}, mesh = {Animals ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Mice, Inbred C57BL ; *Liver/metabolism/drug effects ; Male ; Hepatocytes/metabolism/drug effects ; Lipopolysaccharides/metabolism ; Colon/microbiology/metabolism/drug effects/pathology ; Bacteria/classification/metabolism/genetics/isolation &amp; purification/drug effects ; }, abstract = {Balanced interactions between the enteric microbiota and enterohepatic organs are essential to bile acid homeostasis, and thus normal gastrointestinal function. Disruption of these interactions by cancer treatment instigates bile acid malabsorption, leading to treatment delays, malnutrition, and decreased quality of life. However, the nature of chemotherapy-induced bile acid malabsorption remains poorly characterized with limited treatment options. Therefore, this study sought to characterize changes in hepatic, enteric, and microbial bile acid metabolism in a mouse model of chemotherapy-induced toxicity. Consistent with clinical bile acid malabsorption, chemotherapy increased fecal excretion of primary bile acids and water, while diminishing microbiome diversity, secondary bile acid formation, and small intestinal bile acid signaling. We identified new contributors to pathology of bile acid malabsorption in the forms of lipopolysaccharide-induced cholestasis and colonic crypt hyperplasia from reduced secondary bile acid signaling. Chemotherapy reduced markers of hepatic bile flow and bile acid synthesis, elevated markers of fibrosis and endotoxemia, and altered transcription of genes at all stages of bile acid metabolism. Primary hepatocytes exposed to lipopolysaccharide (but not chemotherapy) replicated chemotherapy-induced transcriptional differences, while gut microbial transplant into germ-free mice replicated very few differences. In the colon, chemotherapy-altered bile acid profiles (particularly higher tauromuricholic acid and lower hyodeoxycholic acid) coincided with crypt hyperplasia. Exposing primary colonoids to hyodeoxycholic acid reduced proliferation, while gut microbiota transplant enhanced proliferation. Together, these investigations reveal complex involvement of the entire microbiota-enterohepatic axis in chemotherapy-induced bile acid malabsorption. Interventions to reduce hepatic lipopolysaccharide exposure and enhance microbial bile acid metabolism represent promising co-therapies to cancer treatment.}, }
@article {pmid39355844, year = {2024}, author = {Ning, S and Zhang, Z and Zhou, C and Wang, B and Liu, Z and Feng, B}, title = {Cross-talk between macrophages and gut microbiota in inflammatory bowel disease: a dynamic interplay influencing pathogenesis and therapy.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1457218}, pmid = {39355844}, issn = {2296-858X}, abstract = {Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic immune-mediated gastrointestinal disorders. The etiology of IBD is multifactorial, involving genetic susceptibility, environmental factors, and a complex interplay between the gut microbiota and the host's immune system. Intestinal resident macrophages play an important role in the pathogenesis and progress of IBD, as well as in maintaining intestinal homeostasis and facilitating tissue repair. This review delves into the intricate relationship between intestinal macrophages and gut microbiota, highlighting their pivotal roles in IBD pathogenesis. We discuss the impact of macrophage dysregulation and the consequent polarization of different phenotypes on intestinal inflammation. Furthermore, we explore the compositional and functional alterations in gut microbiota associated with IBD, including the emerging significance of fungal and viral components. This review also examines the effects of current therapeutic strategies, such as 5-aminosalicylic acid (5-ASA), antibiotics, steroids, immunomodulators, and biologics, on gut microbiota and macrophage function. We underscore the potential of fecal microbiota transplantation (FMT) and probiotics as innovative approaches to modulate the gut microbiome in IBD. The aim is to provide insights into the development of novel therapies targeting the gut microbiota and macrophages to improve IBD management.}, }
@article {pmid39355779, year = {2024}, author = {Zhang, S and Lu, J and Jin, Z and Xu, H and Zhang, D and Chen, J and Wang, J}, title = {Gut microbiota metabolites: potential therapeutic targets for Alzheimer's disease?.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1459655}, pmid = {39355779}, issn = {1663-9812}, abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function, which significantly increases pain and social burden. However, few therapeutic interventions are effective in preventing or mitigating the progression of AD. An increasing number of recent studies support the hypothesis that the gut microbiome and its metabolites may be associated with upstream regulators of AD pathology.<br><br>METHODS: In this review, we comprehensively explore the potential mechanisms and currently available interventions targeting the microbiome for the improvement of AD. Our discussion is structured around modern research advancements in AD, the bidirectional communication between the gut and brain, the multi-target regulatory effects of microbial metabolites on AD, and therapeutic strategies aimed at modulating gut microbiota to manage AD.<br><br>RESULTS: The gut microbiota plays a crucial role in the pathogenesis of AD through continuous bidirectional communication via the microbiota-gut-brain axis. Among these, microbial metabolites such as lipids, amino acids, bile acids and neurotransmitters, especially sphingolipids and phospholipids, may serve as central components of the gut-brain axis, regulating AD-related pathogenic mechanisms including &#x3b2;-amyloid metabolism, Tau protein phosphorylation, and neuroinflammation. Additionally, interventions such as probiotic administration, fecal microbiota transplantation, and antibiotic use have also provided evidence supporting the association between gut microbiota and AD. At the same time, we propose an innovative strategy for treating AD: a healthy lifestyle combined with targeted probiotics and other potential therapeutic interventions, aiming to restore intestinal ecology and microbiota balance.<br><br>CONCLUSION: Despite previous efforts, the molecular mechanisms by which gut microbes act on AD have yet to be fully described. However, intestinal microorganisms may become an essential target for connecting the gut-brain axis and improving the symptoms of AD. At the same time, it requires joint exploration by multiple centers and multiple disciplines.}, }
@article {pmid39351254, year = {2024}, author = {Zhang, ZN and Sang, LX}, title = {Dual-targeted treatment for inflammatory bowel disease: Whether fecal microbiota transplantation can be an important part of it.}, journal = {World journal of gastroenterology}, volume = {30}, number = {36}, pages = {4025-4030}, pmid = {39351254}, issn = {2219-2840}, mesh = {*Fecal Microbiota Transplantation/methods/adverse effects ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Inflammatory Bowel Diseases/therapy/microbiology/immunology ; Treatment Outcome ; Combined Modality Therapy/methods ; Feces/microbiology ; Biological Products/therapeutic use ; Gastrointestinal Agents/therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease. With the emergence of biologics and other therapeutic methods, two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD. Although treatment strategies for IBD are being optimized, their efficacy and risks still warrant further consideration. This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation (FMT) may have for use in combination therapy for IBD. We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment. In this new therapy regimen, FMT represents a promising combination therapy.}, }
@article {pmid39351201, year = {2024}, author = {Frith, ME and Kashyap, PC and Linden, DR and Theriault, B and Chang, EB}, title = {Microbiota-dependent early-life programming of gastrointestinal motility.}, journal = {iScience}, volume = {27}, number = {10}, pages = {110895}, pmid = {39351201}, issn = {2589-0042}, support = {T32 GM150375/GM/NIGMS NIH HHS/United States ; }, abstract = {Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNA sequencing (RNA-seq) of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later-or not at all-showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early-life microbiome in later-life dysmotility.}, }
@article {pmid39350740, year = {2024}, author = {Jochumsen, EA and Kragsnaes, MS and Nilsson, AC and Rasmussen, KF and Ellingsen, T and Juul, MA and Kjeldsen, J and Holm, DK}, title = {'Does this fecal microbiota transplant work?' Quality assurance of capsule based fecal microbiota transplant production.}, journal = {Scandinavian journal of gastroenterology}, volume = {59}, number = {11}, pages = {1234-1239}, doi = {10.1080/00365521.2024.2401460}, pmid = {39350740}, issn = {1502-7708}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Clostridium Infections/therapy ; Female ; Male ; Middle Aged ; Capsules ; Aged ; Quality Assurance, Health Care ; Colonoscopy ; Treatment Outcome ; Clostridioides difficile ; Feces/microbiology ; Adult ; Aged, 80 and over ; Administration, Oral ; }, abstract = {BACKGROUND: Fecal Microbiota Transplant (FMT) is an effective treatment for recurring Clostridioides Difficile Infections (rCDI). FMT administered via oral capsules (caFMT) offers several practical advantages to conventional liquid FMT. We began using caFMT in 2021 imported from an external institution. Based on similar production methods, we began our own caFMT production in 2022. We aimed to evaluate the quality of our caFMT.<br><br>STUDY DESIGN AND METHODS: We created a database of all FMT treatments (n&#x2009;=&#x2009;180) provided by our institution. Quality of all FMT was evaluated by treatment success rates. We compared our caFMT to the imported caFMT.<br><br>RESULTS: Our caFMT yielded similar success rates compared to that of the imported caFMT, 65% (CI 95% 58-72%) and 72% (CI 95% 66-79%) respectively. FMT administered via colonoscopy had a significantly higher success rate, 79% (CI 95% 73-85%) than own our caFMT and other routes of administration. The combined success rate of treatments increased notably for all routes of administration when repeating FMT after prior failure.<br><br>DISCUSSION: The fact that our caFMT compared similarly to the imported caFMT was viewed as a success in terms of quality assurance. Our caFMT had a slightly lower success rates compared to data from other studies, but could be affected by several other factors than our FMT-production methods. A lower success rate of caFMT compared to FMT via colonoscopy is acceptable due to the practical advantages offed by caFMT. Our study serves as a practical example, proving that of the standardization of caFMT production is indeed viable.}, }
@article {pmid39349020, year = {2024}, author = {Dutta, R and Stothers, L and Ackerman, AL}, title = {Manipulating the Gut Microbiome in Urinary Tract Infection-Prone Patients.}, journal = {The Urologic clinics of North America}, volume = {51}, number = {4}, pages = {525-536}, doi = {10.1016/j.ucl.2024.07.016}, pmid = {39349020}, issn = {1558-318X}, mesh = {Humans ; *Urinary Tract Infections/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Female ; Anti-Bacterial Agents/therapeutic use ; Vaccinium macrocarpon ; }, abstract = {Although antibiotics remain the mainstay of urinary tract infection treatment, many affected women can be caught in a vicious cycle in which antibiotics given to eradicate one infection predispose them to develop another. This effect is primarily mediated by disturbances in the gut microbiome that both directly enrich for uropathogenic overgrowth and induce systemic alterations in inflammation, tissue permeability, and metabolism that also decrease host resistance to infection recurrences. Here, we discuss nonantibiotic approaches to manipulating the gut microbiome to reverse the systemic consequences of antibiotics, including cranberry supplementation and other dietary approaches, probiotic administration, and fecal microbiota transplantation.}, }
@article {pmid39349017, year = {2024}, author = {Werneburg, GT and Hsieh, MH}, title = {Clinical Microbiome Testing for Urology.}, journal = {The Urologic clinics of North America}, volume = {51}, number = {4}, pages = {493-504}, doi = {10.1016/j.ucl.2024.06.007}, pmid = {39349017}, issn = {1558-318X}, mesh = {Humans ; *Microbiota ; *Urinary Tract Infections/diagnosis/microbiology ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {The urine culture is imperfect, and a series of alternative approaches are in development to assist in diagnosis, treatment, and prevention of urinary tract infection (UTI). Culture-independent approaches typically do not distinguish between viable and nonviable bacteria, and are generally not included in current clinical guidance. Next-generation sequencing may play an important future role in precise targeting of antibiotic treatment of asymptomatic bacteriuria prior to endourologic surgery or in pregnancy. Future studies are needed to determine whether microbiota modulation could prevent UTI. Possible modulation mechanisms may include fecal microbiota transplant, application of topical vaginal estrogen or probiotics, and bacteriophage therapy.}, }
@article {pmid39348436, year = {2024}, author = {Liu, C and Cyphert, EL and Stephen, SJ and Wang, B and Morales, AL and Nixon, JC and Natsoulas, NR and Garcia, M and Carmona, PB and Vill, AC and Donnelly, E and Brito, IL and Vashishth, D and Hernandez, CJ}, title = {Microbiome-induced increases and decreases in bone matrix strength can be initiated after skeletal maturity.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {39}, number = {11}, pages = {1621-1632}, pmid = {39348436}, issn = {1523-4681}, support = {R01 AG067997/AG/NIA NIH HHS/United States ; R56 AG067997/AG/NIA NIH HHS/United States ; //NIH/ ; F32AG076244/GF/NIH HHS/United States ; }, mesh = {Animals ; Male ; Female ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Femur/microbiology/drug effects ; Bone Matrix/metabolism ; Mice, Inbred C57BL ; }, abstract = {Recent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16 weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n = 143 total, n = 12-17/group/sex) were allocated into five study groups: (1) Unaltered, (2) Continuous (dosing 4-24 weeks of age), (3) Delayed (dosing only 16-24 weeks of age), (4) Initial (dosing 4-16 weeks of age, suspended at 16 weeks), and (5) Reconstituted (dosing from 4-16 weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24 weeks of age. In males, bone matrix strength in the femur was 25%-35% less than expected by geometry in mice from the Continuous (p = 0.001), Delayed (p = 0.005), and Initial (p = 0.040) groups as compared to Unaltered. Reconstitution of the gut microbiota led to a bone matrix strength similar to Unaltered animals (p = 0.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating a sex-dependent response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed with Raman spectroscopy. Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16 weeks) was small; suggesting that microbiome-induced changes in bone matrix occurred without osteoblast/osteoclast turnover through a yet unidentified mechanism. These findings provide evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.}, }
@article {pmid39347394, year = {2024}, author = {Zhao, Y and Guo, K and Yan, Y and Jiang, B}, title = {Cucurbitacin IIb alleviates colitis via regulating gut microbial composition and metabolites.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e38051}, pmid = {39347394}, issn = {2405-8440}, abstract = {Cucurbitacin IIb, a member of the triterpenoid family, exerts beneficial effects on intestinal diseases, including enteritis and bacillary dysentery. However, its effects and mechanisms of action on colitis have not yet been explored. In this study, we used a mouse model of dextran sulfate sodium (DSS)-induced colitis and explored the effects of cucurbitacin IIb on colitis symptoms, inflammatory responses, microbiota, and metabolite profiles. The results showed that cucurbitacin IIb alleviated colitis symptoms including body weight loss, an increase in the disease activity index, and elevated levels of myeloperoxidase and eosinophil peroxidase content. Additionally, it ameliorated intestinal morphology impairment, reduced the phosphorylation of NFκB protein, and mitigated accumulation of pro-inflammatory cytokines IL-6 and IL-1β. Furthermore, cucurbitacin IIb alleviated alterations in gut microbial composition and metabolites in DSS-treated mice. However, antibiotic treatment diminishes the beneficial effects of cucurbitacin IIb on colitis. We further found that transplantation of fresh feces or heat-inactivated feces from mice treated with cucurbitacin IIb to DSS-treated mice alleviated colitis, similar to the effects of cucurbitacin IIb. Collectively, our results suggest that cucurbitacin IIb exerted anti-inflammatory effects in colitis by regulating the microbiota composition and metabolites, thereby alleviating colitis symptoms.}, }
@article {pmid39346901, year = {2024}, author = {Alatan, H and Liang, S and Shimodaira, Y and Wu, X and Hu, X and Wang, T and Luo, J and Iijima, K and Jin, F}, title = {Supplementation with Lactobacillus helveticus NS8 alleviated behavioral, neural, endocrine, and microbiota abnormalities in an endogenous rat model of depression.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1407620}, pmid = {39346901}, issn = {1664-3224}, mesh = {Animals ; Rats ; *Gastrointestinal Microbiome/drug effects ; *Lactobacillus helveticus ; *Probiotics/administration &amp; dosage/therapeutic use ; *Disease Models, Animal ; *Rats, Inbred WKY ; *Depression/immunology/metabolism ; Male ; *Brain-Gut Axis ; Behavior, Animal ; Rats, Wistar ; }, abstract = {INTRODUCTION: Major depressive disorder is a condition involving microbiota-gut-brain axis dysfunction. Increasing research aims to improve depression through gut microbiota regulation, including interventions such as probiotics, prebiotics, and fecal microbiota transplants. However, most research focuses on exogenous depression induced by chronic stress or drugs, with less attention given to endogenous depression. Additionally, research on gut mycobiota in depression is significantly less than that on gut bacteria.<br><br>METHODS: In the present study, Wistar-Kyoto rats were used as an endogenous depression and treatment-resistant depression model, while Wistar rats served as controls. Differences between the two rat strains in behavior, gut bacteria, gut mycobiota, nervous system, endocrine system, immune system, and gut barrier were evaluated. Additionally, the effects of Lactobacillus helveticus NS8 supplementation were investigated.<br><br>RESULTS: Wistar-Kyoto rats demonstrated increased depressive-like behaviors in the forced swimming test, reduced sucrose preference in the sucrose preference test, and decreased locomotor activity in the open field test. They also exhibited abnormal gut bacteria and mycobiota, characterized by higher bacterial &#x3b1;-diversity but lower fungal &#x3b1;-diversity, along with increased butyrate, L-tyrosine, and L-phenylalanine biosynthesis from bacteria. Furthermore, these rats showed dysfunction in the microbiota-gut-brain axis, evidenced by a hypo-serotonergic system, hyper-noradrenergic system, defective hypothalamic-pituitary-adrenal axis, compromised gut barrier integrity, heightened serum inflammation, and diminished gut immunity. A 1-month L. helveticus NS8 intervention increased the fecal abundance of L. helveticus; reduced the abundance of Bilophila and Debaryomycetaceae; decreased immobility time but increased climbing time in the forced swimming test; reduced hippocampal corticotropin-releasing hormone levels; decreased hypothalamic norepinephrine levels; increased hippocampal glucocorticoid receptor, brain-derived neurotrophic factor dopamine, and 5-hydroxyindoleacetic acid content; and improved the gut microbiota, serotonergic, and noradrenergic system.<br><br>CONCLUSION: The depressive phenotype of Wistar-Kyoto rats is not only attributed to their genetic context but also closely related to their gut microbiota. Abnormal gut microbiota and a dysfunctional microbiota-gut-brain axis play important roles in endogenous depression, just as they do in exogenous depression. Supplementing with probiotics such as L. helveticus NS8 is likely a promising approach to improve endogenous depression and treatment-resistant depression.}, }
@article {pmid39345742, year = {2024}, author = {Liu, X and Wang, Z and Teng, C and Wang, Z}, title = {Changes in gut microbiota and metabolites of mice with intravenous graphene oxide-induced embryo toxicity.}, journal = {Toxicological research}, volume = {40}, number = {4}, pages = {571-584}, pmid = {39345742}, issn = {1976-8257}, abstract = {UNLABELLED: The expanding applications of graphene oxide (GO) nanomaterials have attracted interest in understanding their potential adverse effects on embryonic and fetal development. Numerous studies have revealed the importance of the maternal gut microbiota in pregnancy. In this study, we established a mouse GO exposure model to evaluate embryo toxicity induced by intravenous administration of GO during pregnancy. We also explored the roles of gut microbiota and fecal metabolites using a fecal microbiota transplantation (FMT) intervention model. We found that administration of GO at doses up to 1.25 mg/kg caused embryo toxicity, characterized by significantly increased incidences of fetal resorption, stillbirths, and decreased birth weight. In pregnant mice with embryo toxicity, the richness of the maternal gut microbiota was dramatically decreased, and components of the microbial community were disturbed. FMT alleviated the decrease in birth weight by remodeling the gut microbiota, especially via upregulation of the Firmicutes/Bacteroidetes ratio. We subsequently used untargeted metabolomics to identify characteristic fecal metabolites associated with GO exposure. These metabolites were closely correlated with the phyla Actinobacteria, Proteobacteria, and Cyanobacteria. Our findings offer new insights into the embryo toxic effects of GO exposure during pregnancy; they emphasize the roles of gut microbiota-metabolite interactions in adverse pregnancy outcomes induced by GO or other external exposures, as demonstrated through FMT intervention.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43188-024-00242-3.}, }
@article {pmid39338992, year = {2024}, author = {Lim, X and Ooi, L and Ding, U and Wu, HHL and Chinnadurai, R}, title = {Gut Microbiota in Patients Receiving Dialysis: A Review.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, pmid = {39338992}, issn = {2076-0817}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Renal Dialysis/adverse effects ; *Dysbiosis/microbiology ; *Kidney Failure, Chronic/therapy/microbiology ; Renal Insufficiency, Chronic/therapy/microbiology/complications ; Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; }, abstract = {The human gut microbiota constitutes a complex community of microorganisms residing within the gastrointestinal tract, encompassing a vast array of species that play crucial roles in health and disease. The disease processes involved in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are now increasingly established to result in dysregulation of gut microbiota composition and function. Gut microbiota dysbiosis has been associated with poor clinical outcomes and all-cause mortality in patients with ESKD, particularly individuals receiving dialysis. Prior studies highlighted various factors that affect gut microbiota dysbiosis in CKD and ESKD. These include, but are not limited to, uraemic toxin accumulation, chronic inflammation, immune dysfunction, medications, and dietary restrictions and nutritional status. There is a lack of studies at present that focus on the evaluation of gut microbiota dysbiosis in the context of dialysis. Knowledge on gut microbiota changes in this context is important for determining their impact on dialysis-specific and overall outcomes for this patient cohort. More importantly, evaluating gut microbiota composition can provide information into potential targets for therapeutic intervention. Identification of specific microbial signatures may result in further development of personalised treatments to improve patient outcomes and mitigate complications during dialysis. Optimising gut microbiota through various therapeutic approaches, including dietary adjustments, probiotics, prebiotics, medications, and faecal transplantation, have previously demonstrated potential in multiple medical conditions. It remains to be seen whether these therapeutic approaches are effective within the dialysis setting. Our review aims to evaluate evidence relating to alterations in the gut microbiota of patients undergoing dialysis. A growing body of evidence pointing to the complex yet significant relationship which surrounds gut microbiota and kidney health emphasises the importance of gut microbial balance to improve outcomes for individuals receiving dialysis.}, }
@article {pmid39338430, year = {2024}, author = {Fanizzi, F and D'Amico, F and Zanotelli Bombassaro, I and Zilli, A and Furfaro, F and Parigi, TL and Cicerone, C and Fiorino, G and Peyrin-Biroulet, L and Danese, S and Allocca, M}, title = {The Role of Fecal Microbiota Transplantation in IBD.}, journal = {Microorganisms}, volume = {12}, number = {9}, pages = {}, pmid = {39338430}, issn = {2076-2607}, abstract = {Gut microbiota dysbiosis has a critical role in the pathogenesis of inflammatory bowel diseases, prompting the exploration of novel therapeutic approaches like fecal microbiota transplantation, which involves the transfer of fecal microbiota from a healthy donor to a recipient with the aim of restoring a balanced microbial community and attenuating inflammation. Fecal microbiota transplantation may exert beneficial effects in inflammatory bowel disease through modulation of immune responses, restoration of mucosal barrier integrity, and alteration of microbial metabolites. It could alter disease course and prevent flares, although long-term durability and safety data are lacking. This review provides a summary of current evidence on fecal microbiota transplantation in inflammatory bowel disease management, focusing on its challenges, such as variability in donor selection criteria, standardization of transplant protocols, and long-term outcomes post-transplantation.}, }
@article {pmid39338312, year = {2024}, author = {Qi, X and Sun, H and Liu, J and Cong, M and Zhang, X and Yan, Y and Xia, Z and Liu, T and Zhao, J}, title = {Phenylethanol Glycoside from Cistanche tubulosa Attenuates BSA-Induced Liver Fibrosis in Rats by Modulating the Gut Microbiota-Liver Axis.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {9}, pages = {}, pmid = {39338312}, issn = {1424-8247}, support = {2022D01D36//This work was financially supported by the Key project of Natural Science Foundation of Xinjiang Uygur Autonomous Region in China/ ; }, abstract = {This study aimed to investigate the effect of phenylethanol glycoside from Cistanche tubulosa (CPhGs) on the prevention of bovine serum albumin (BSA)-induced hepatic fibrosis in rats. Investigation of the mechanisms of the anti-hepatic fibrosis effect was focused on CPhGs' influence on the "gut-liver" regulation, including the gut microbiota, intestinal barrier, systemic lipopolysaccharide (LPS) concentration, and LPS-related signaling pathway. The results show that CPhGs restored the diversity of gut microbiota, increased the relative abundance of Bacteroidetes, and decreased the relative abundance of Firmicutes and Proteobacteria in the fibrotic rats. In addition, CPhGs promoted the enrichment of probiotics such as Blautia, Oscillospira, Ruminococcus, Odoribacter, Bacteroides, and Parabacteroides in intestines of these rats. Furthermore, CPhGs reduced histopathological injury in the intestine and restored the tight junctions of the intestine by increasing the expression of ZO-1, occludin, and E-cadherin. CPhGs efficiently reduced serum LPS and liver lipopolysaccharide-binding protein (LBP) levels and inhibited the LPS-TLR4/MyD88/NF-κB pathway, which is related to protein expression in the liver. Correlation analysis confirmed that these beneficial bacteria were negatively associated with pathological damage, while LPS and harmful bacteria were positively associated with liver injury. Our fecal microbiota transplantation (FMT) experiment confirmed that gut microbiota is an important part of disease progression and that CPhGs is useful for the prevention and treatment of hepatic fibrosis. Our data demonstrate that the anti-hepatic fibrosis mechanism of CPhGs was mediated by regulation of the "gut-liver" axis. These results can stimulate consideration for its use in clinical practices.}, }
@article {pmid39337526, year = {2024}, author = {Missiego-Beltrán, J and Beltrán-Velasco, AI}, title = {The Role of Microbial Metabolites in the Progression of Neurodegenerative Diseases-Therapeutic Approaches: A Comprehensive Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337526}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; *Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation ; Disease Progression ; Blood-Brain Barrier/metabolism ; Oxidative Stress ; Fatty Acids, Volatile/metabolism ; }, abstract = {The objective of this review is to provide a comprehensive examination of the role of microbial metabolites in the progression of neurodegenerative diseases, as well as to investigate potential therapeutic interventions targeting the microbiota. A comprehensive literature search was conducted across the following databases: PubMed, Scopus, Web of Science, ScienceDirect, and Wiley. Key terms related to the gut microbiota, microbial metabolites, neurodegenerative diseases, and specific metabolic products were used. The review included both preclinical and clinical research articles published between 2000 and 2024. Short-chain fatty acids have been demonstrated to play a crucial role in modulating neuroinflammation, preserving the integrity of the blood-brain barrier, and influencing neuronal plasticity and protection. Furthermore, amino acids and their derivatives have been demonstrated to exert a significant influence on CNS function. These microbial metabolites impact CNS health by regulating intestinal permeability, modulating immune responses, and directly influencing neuroinflammation and oxidative stress, which are integral to neurodegenerative diseases. Therapeutic strategies, including prebiotics, probiotics, dietary modifications, and fecal microbiota transplantation have confirmed the potential to restore microbial balance and enhance the production of neuroprotective metabolites. Furthermore, novel drug developments based on microbial metabolites present promising therapeutic avenues. The gut microbiota and its metabolites represent a promising field of research with the potential to advance our understanding of and develop treatments for neurodegenerative diseases.}, }
@article {pmid39337098, year = {2024}, author = {Tîrziu, AT and Susan, M and Susan, R and Sonia, T and Harich, OO and Tudora, A and Varga, NI and Tiberiu-Liviu, D and Avram, CR and Boru, C and Munteanu, M and Horhat, FG}, title = {From Gut to Eye: Exploring the Role of Microbiome Imbalance in Ocular Diseases.}, journal = {Journal of clinical medicine}, volume = {13}, number = {18}, pages = {}, pmid = {39337098}, issn = {2077-0383}, abstract = {Background: The gut microbiome plays a crucial role in human health, and recent research has highlighted its potential impact on ocular health through the gut-eye axis. Dysbiosis, or an imbalance in the gut microbiota, has been implicated in various ocular diseases. Methods: A comprehensive literature search was conducted using relevant keywords in major electronic databases, prioritizing recent peer-reviewed articles published in English. Results: The gut microbiota influences ocular health through immune modulation, maintenance of the blood-retinal barrier, and production of beneficial metabolites. Dysbiosis can disrupt these mechanisms, contributing to ocular inflammation, tissue damage, and disease progression in conditions such as uveitis, age-related macular degeneration, diabetic retinopathy, dry eye disease, and glaucoma. Therapeutic modulation of the gut microbiome through probiotics, prebiotics, synbiotics, and fecal microbiota transplantation shows promise in preclinical and preliminary human studies. Conclusions: The gut-eye axis represents a dynamic and complex interplay between the gut microbiome and ocular health. Targeting the gut microbiome through innovative therapeutic strategies holds potential for improving the prevention and management of various ocular diseases.}, }
@article {pmid39334498, year = {2024}, author = {De Filippo, C and Chioccioli, S and Meriggi, N and Troise, AD and Vitali, F and Mejia Monroy, M and Özsezen, S and Tortora, K and Balvay, A and Maudet, C and Naud, N and Fouché, E and Buisson, C and Dupuy, J and Bézirard, V and Chevolleau, S and Tondereau, V and Theodorou, V and Maslo, C and Aubry, P and Etienne, C and Giovannelli, L and Longo, V and Scaloni, A and Cavalieri, D and Bouwman, J and Pierre, F and Gérard, P and Guéraud, F and Caderni, G}, title = {Gut microbiota drives colon cancer risk associated with diet: a comparative analysis of meat-based and pesco-vegetarian diets.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {180}, pmid = {39334498}, issn = {2049-2618}, support = {JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; Expression of interest # 895//HDHL INTIMIC-Knowledge Platform on food, diet, intestinal microbiomics and human health/ ; Expression of interest # 895//HDHL INTIMIC-Knowledge Platform on food, diet, intestinal microbiomics and human health/ ; PE00000003//National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3 - Call for tender No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union - NextGenerationEU; Project title "ON Foods - Research and innovation network on food and nutrition Sustainability, Safety and Security - Working ON Foods"/ ; PE00000003//National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3 - Call for tender No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union - NextGenerationEU; Project title "ON Foods - Research and innovation network on food and nutrition Sustainability, Safety and Security - Working ON Foods"/ ; PE00000003//National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3 - Call for tender No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union - NextGenerationEU; Project title "ON Foods - Research and innovation network on food and nutrition Sustainability, Safety and Security - Working ON Foods"/ ; ECS00000017//European Union - NextGenerationEU - National Recovery and Resilience Plan, Mission 4 Component 2 - Investment 1.5 - THE - Tuscany Health Ecosystem/ ; ECS00000017//European Union - NextGenerationEU - National Recovery and Resilience Plan, Mission 4 Component 2 - Investment 1.5 - THE - Tuscany Health Ecosystem/ ; G. Caderni//University of Florence (Fondo ex-60%), Italy/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Rats ; *Colonic Neoplasms/microbiology/etiology ; *Diet, Vegetarian/adverse effects ; *Feces/microbiology ; *Fecal Microbiota Transplantation ; *RNA, Ribosomal, 16S/genetics ; Male ; Bacteria/classification/isolation &amp; purification/genetics/metabolism ; Diet/adverse effects ; Azoxymethane ; Meat/adverse effects/microbiology ; Colorectal Neoplasms/microbiology/etiology ; Disease Models, Animal ; Humans ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) risk is strongly affected by dietary habits with red and processed meat increasing risk, and foods rich in dietary fibres considered protective. Dietary habits also shape gut microbiota, but the role of the combination between diet, the gut microbiota, and the metabolite profile on CRC risk is still missing an unequivocal characterisation.<br><br>METHODS: To investigate how gut microbiota affects diet-associated CRC risk, we fed Apc-mutated PIRC rats and azoxymethane (AOM)-induced rats the following diets: a high-risk red/processed meat-based diet (MBD), a normalised risk diet (MBD with &#x3b1;-tocopherol, MBDT), a low-risk pesco-vegetarian diet (PVD), and control diet. We then conducted faecal microbiota transplantation (FMT) from PIRC rats to germ-free rats treated with AOM and fed a standard diet for 3&#xa0;months. We analysed multiple tumour markers and assessed the variations in the faecal microbiota using 16S rRNA gene sequencing together with targeted- and untargeted-metabolomics analyses.<br><br>RESULTS: In both animal models, the PVD group exhibited significantly lower colon tumorigenesis than the MBD ones, consistent with various CRC biomarkers. Faecal microbiota and its metabolites also revealed significant diet-dependent profiles. Intriguingly, when faeces from PIRC rats fed these diets were transplanted into germ-free rats, those transplanted with MBD faeces developed a higher number of preneoplastic lesions together with distinctive diet-related bacterial and metabolic profiles. PVD determines a selection of nine taxonomic markers mainly belonging to Lachnospiraceae and Prevotellaceae families exclusively associated with at least two different animal models, and within these, four taxonomic markers were shared across all the three animal models. An inverse correlation between nonconjugated bile acids and bacterial genera mainly belonging to the Lachnospiraceae and Prevotellaceae families (representative of the PVD group) was present, suggesting a potential mechanism of action for the protective effect of these genera against CRC.<br><br>CONCLUSIONS: These results highlight the protective effects of PVD while reaffirming the carcinogenic properties of MBD diets. In germ-free rats, FMT induced changes reminiscent of dietary effects, including heightened preneoplastic lesions in MBD rats and the transmission of specific diet-related bacterial and metabolic profiles. Importantly, to the best of our knowledge, this is the first study showing that diet-associated cancer risk can be transferred with faeces, establishing gut microbiota as a determinant of diet-associated CRC risk. Therefore, this study marks the pioneering demonstration of faecal transfer as a means of conveying diet-related cancer risk, firmly establishing the gut microbiota as a pivotal factor in diet-associated CRC susceptibility. Video Abstract.}, }
@article {pmid39333864, year = {2024}, author = {Huang, F and Deng, Y and Zhou, M and Tang, R and Zhang, P and Chen, R}, title = {Fecal microbiota transplantation from patients with polycystic ovary syndrome induces metabolic disorders and ovarian dysfunction in germ-free mice.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {364}, pmid = {39333864}, issn = {1471-2180}, support = {82201781//National Natural Science Foundation of China/ ; 81871141//National Natural Science Foundation of China/ ; 2022-PUMCH-B-123//National High-Level Hospital Clinical Research Funding/ ; 2018YFC1004801//National Key Research and Development Program/ ; 2020-I2M-CT-B-040//CAMS Innovation Fund for Medical Sciences (CIFMS)/ ; }, mesh = {*Polycystic Ovary Syndrome/microbiology/therapy ; Animals ; *Fecal Microbiota Transplantation ; Female ; Mice ; *Gastrointestinal Microbiome ; Humans ; *Dysbiosis/microbiology ; Feces/microbiology ; Metabolic Diseases/microbiology/etiology/therapy ; Bacteria/classification/isolation &amp; purification/genetics ; Insulin Resistance ; Ovary/microbiology ; Germ-Free Life ; Disease Models, Animal ; Adult ; }, abstract = {BACKGROUND: Dysbiosis of the microbiome is a key hallmark of polycystic ovary syndrome (PCOS). However, the interaction between the host and microbiome and its relevance to the pathogenesis of PCOS remain unclear.<br><br>METHODS: To evaluate the role of the commensal gut microbiome in PCOS, we gavaged germ-free mice with the fecal microbiota from patients with PCOS or healthy individuals and evaluated the reproductive endocrine features of the recipient mice.<br><br>RESULTS: Mice transplanted with fecal microbiota from PCOS patients and those transplanted from healthy controls presented different bacterial profiles and reproductive endocrine features. The fecal microbiota of the mice in the PCOS group was enriched in Phocaeicola, Mediterraneibacter, Oscillospiraceae, Lawsonibacter and Rikenellaceae. Fecal microbiota transplantation (FMT) from PCOS patients induced increased disruption of ovarian functions, lipo-metabolic disturbance, insulin resistance and an obese-like phenotype in recipient mice.<br><br>CONCLUSION: Our findings suggest that the microbiome may govern the set point of PCOS-bearing individuals and that gut ecosystem manipulation may be a useful marker and target for the management of PCOS.}, }
@article {pmid39333064, year = {2024}, author = {Chen, X and Chen, X and Yan, D and Zhang, N and Fu, W and Wu, M and Ge, F and Wang, J and Li, X and Geng, M and Wang, J and Tang, D and Liu, J}, title = {GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8278}, pmid = {39333064}, issn = {2041-1723}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Male ; Mice ; *Pancreatitis/immunology/microbiology/metabolism ; *Mice, Inbred C57BL ; *Disease Models, Animal ; Macrophages/immunology/metabolism ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Humans ; Metabolomics ; }, abstract = {Despite recent advances, severe acute pancreatitis (SAP) remains a lethal inflammation with limited treatment options. Here, we provide compelling evidence of GV-971 (sodium oligomannate), an anti-Alzheimer's medication, as being a protective agent in various male mouse SAP models. Microbiome sequencing, along with intestinal microbiota transplantation and mass cytometry technology, unveil that GV-971 reshapes the gut microbiota, increasing Faecalibacterium populations and modulating both peripheral and intestinal immune systems. A metabolomics analysis of cecal contents from GV-971-treated SAP mice further identifies short-chain fatty acids, including propionate and butyrate, as key metabolites in inhibiting macrophage M1 polarization and subsequent lethal inflammation by blocking the MAPK pathway. These findings suggest GV-971 as a promising therapeutic for SAP by targeting the microbiota metabolic immune axis.}, }
@article {pmid39331938, year = {2024}, author = {Zhao, Y and Qiu, P and Shen, T}, title = {Gut microbiota and eye diseases: A review.}, journal = {Medicine}, volume = {103}, number = {39}, pages = {e39866}, pmid = {39331938}, issn = {1536-5964}, support = {NO.2023C03089//the Research and Development Plan of Zhejiang Science and Technology Department/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Eye Diseases/microbiology/therapy/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Recent studies reveal that alterations in gut microbiota play a significant role in the progression of various diseases, including those affecting the eyes. The association between gut microbiota and eye health is an emerging focus of research. This review seeks to summarize the connection between the gut microbiome and specific eye conditions, such as ocular surface diseases, funduscopic disorders and immune-mediated eye diseases. Gut microbiota may influence these conditions by regulating the immune system or altering metabolites, thereby contributing to disease development. Strategies like probiotics, antibiotics, dietary modifications, and fecal transplants show promise in addressing these issues. This review examines how the gut microbiome may be linked to the pathogenesis of eye diseases, providing fresh therapeutic perspectives for ophthalmology.}, }
@article {pmid39330818, year = {2024}, author = {Hanifeh, M and Scarsella, E and Rojas, CA and Ganz, HH and Huhtinen, M and Laine, T and Spillmann, T}, title = {Oral Fecal Microbiota Transplantation in Dogs with Tylosin-Responsive Enteropathy-A Proof-of-Concept Study.}, journal = {Veterinary sciences}, volume = {11}, number = {9}, pages = {}, pmid = {39330818}, issn = {2306-7381}, support = {V3130001//Orion Corporation (Finland)/ ; }, abstract = {A clinical trial was conducted to evaluate the effect of fecal microbiota transplantation (FMT) on the canine chronic enteropathy clinical activity index (CCECAI), fecal consistency, and microbiome of dogs with tylosin-responsive enteropathy (TRE). The trial consisted of four phases: (1) screening with discontinuation of tylosin for 4 weeks, (2) inclusion with re-introduction of tylosin for 3-7 days, (3) treatment with FMT/placebo for 4 weeks, and (4) post-treatment with follow-up for 4 weeks after treatment cessation. The study found that the treatment efficacy of FMT (71.4%) was slightly higher than that of placebo (50%), but this difference was not statistically significant due to underpowering. The most abundant bacterial species detected in the fecal microbiomes of dogs with TRE before FMT or placebo treatment were Blautia hansenii, Ruminococcus gnavus, Escherichia coli, Clostridium dakarense, Clostridium perfringens, Bacteroides vulgatus, and Faecalimonas umbilicata. After FMT, the microbiomes exhibited increases in Clostridium dakarense, Clostridium paraputrificum, and Butyricicoccus pullicaecorum. The microbiome alpha diversity of TRE dogs was lower when on tylosin treatment compared to healthy dogs, but it increased after treatment in both the FMT and placebo groups. Comparisons with the stool donor showed that, on average, 30.4% of donor strains were engrafted in FMT recipients, with the most common strains being several Blautia sp., Ruminococcus gnavus, unclassified Lachnoclostridium, Collinsella intestinalis, and Fournierella massiliensis.}, }
@article {pmid39329364, year = {2024}, author = {Rani, M and Akhilesh,  and Chouhan, D and Uniyal, A and Tiwari, V}, title = {Fecal Microbiota Transplantation-Mediated Rebalancing of the Gut-Brain Axis Alleviates Cisplatin-Induced Neuropathic Pain.}, journal = {ACS chemical neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1021/acschemneuro.4c00267}, pmid = {39329364}, issn = {1948-7193}, abstract = {Chemotherapy-induced neuropathic pain (CINP) presents a significant challenge in cancer treatment, necessitating novel therapeutic approaches. The intricate relationship between CINP and the gut-brain axis indicates a crucial role for the gut microbiota in pain modulation during cancer therapy. In this study, we investigated the effect of gut microbiota and their modulation on CINP in rats. Cisplatin administration (20 mg/kg, ip) disrupted the integrity of the blood-spinal cord barrier, as evidenced by reduced expression of tight junction proteins occludin and claudin-5 and increased leakage of pro-inflammatory cytokines into the spinal cord. Fecal microbiota transplantation (FMT, 0.5 mL of P.O.) from healthy rats over 21 days restored barrier integrity, as confirmed by Evan's blue assay. FMT intervention halted the progression of cisplatin-induced pain, demonstrated through a battery of pain assays assessing mechanical, thermal, and cold allodynia alongside hyperalgesia measurements. Additionally, FMT treatment reduced oxidative stress and modulated neuro-inflammatory markers, resulting in a rebalanced cytokine profile with decreased levels of neuro-inflammatory cytokines (IL-6 and TNFα) and increased expression of the anti-inflammatory cytokine IL-10. Gut microbiota-mediated IL-1β/NF-κB signaling emerged as a critical factor in leukocyte recruitment and microglial activation, highlighting the gut-brain axis as a key regulatory nexus in managing cisplatin-induced neuropathic pain. These findings underscore the therapeutic potential of targeting gut microbiota modulation as a promising strategy for alleviating CINP and improving the well-being of cancer patients undergoing chemotherapy.}, }
@article {pmid39326141, year = {2024}, author = {Hu, T and Zhu, Y and Zhou, X and Ye, M and Wang, X and Lu, C and Wang, Y}, title = {Baicalein ameliorates SEB-induced acute respiratory distress syndrome in a microbiota-dependent manner.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156049}, doi = {10.1016/j.phymed.2024.156049}, pmid = {39326141}, issn = {1618-095X}, mesh = {Animals ; *Flavanones/pharmacology ; *Respiratory Distress Syndrome/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Mice ; Male ; Scutellaria baicalensis/chemistry ; Mice, Inbred C57BL ; Lung/drug effects ; Myeloid Differentiation Factor 88/metabolism ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Enterotoxins ; }, abstract = {BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by sudden and extensive pulmonary inflammation, with a mortality rate of approximately 40 %. Presently, there is no effective treatment to prevent or reverse its severe consequences. Baicalein (BAI) is a natural vicinal trihydroxyflavone and has been identified as the core quality marker of Scutellariae baicalensis for its effect on lung inflammation. However, its oral bioavailability is limited. The majority of studies that investigate BAI's in vivo mechanisms use injection techniques. Currently, there is no clear understanding of the mechanisms by which low-bioavailable BAI functions orally.<br><br>PURPOSE: This study aimed to evaluate the efficiency of BAI in ARDS mice and its underlying mechanisms.<br><br>STUDY DESIGN AND METHODS: Behavioral experiments, histological analysis, immunofluorescence staining, flow cytometry of immune cells, qRT-PCR, and ELISA analysis were performed to evaluate the efficiency of BAI in ARDS mice. Lung tissues transcriptomic-based analyses were performed to detect the differentially expressed genes and biological pathways. Fecal samples were subjected to microbial 16S rRNA analysis and untargeted metabolomics analysis in order to identify the specific flora and metabolites associated with BAI. Furthermore, antibiotic cocktail treatment and fecal microbiota transplantation were used to elucidate the gut microbiota-mediated effects on ARDS.<br><br>RESULTS: In our study, we first find that oral administration of BAI effectively mitigates staphylococcal enterotoxin B-induced ARDS. BAI can alleviate gut dysbiosis and regulate the Toll-like signaling pathway and amino acid metabolism. The protective effects of BAI against ARDS are gut microbiota dependent. Modulation of gut microbiota increases the production of short-chain fatty acids and enhances lung barrier function, which is consistent with the therapeutic interventions with BAI. Notably, BAI greatly enriches the abundance of Prevotellaceae, a butyrate-producing bacterial family, exhibiting a positive correlation with key differentially expressed genes in the TLR4/MyD88 signaling cascades.<br><br>CONCLUSION: BAI emerges as a potential prebiotic agent to attenuate ARDS, and targeting specific microbial species may offer an innovative therapeutic approach to investigate other flavonoids with limited bioavailability.}, }
@article {pmid39324491, year = {2024}, author = {Pu, D and Yao, Y and Zhou, C and Liu, R and Wang, Z and Liu, Y and Wang, D and Wang, B and Wang, Y and Liu, Z and Zhang, Z and Feng, B}, title = {FMT rescues mice from DSS-induced colitis in a STING-dependent manner.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2397879}, pmid = {39324491}, issn = {1949-0984}, mesh = {Animals ; Humans ; Mice ; *Colitis/therapy/chemically induced/immunology ; Colon/microbiology/immunology/pathology ; *Dextran Sulfate/adverse effects ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Macrophages/immunology ; *Membrane Proteins/genetics/metabolism ; *Mice, Inbred C57BL ; Th1 Cells/immunology ; Th17 Cells/immunology ; Th2 Cells/immunology ; }, abstract = {Fecal microbiota transplantation (FMT) is currently a promising therapy for inflammatory bowel disease (IBD). However, clinical studies have shown that there is an obvious individual difference in the efficacy of FMT. Therefore, it is a pressing issue to identify the factors that influence the efficacy of FMT and find ways to screen the most suitable patients for this therapy. In this work, we targeted the stimulator of interferon genes (STING), a DNA-sensing protein that regulates host-defense. By comparing the differential efficacy of FMT in mice with different expression level of STING, it is revealed that FMT therapy provides treatment for DSS-induced colitis in a STING-dependent manner. Mechanistically, FMT exerts a regulatory effect on the differentiation of intestinal Th17 cells and macrophages, splenic Th1 and Th2 cells, as well as Th1 cells of the mesenteric lymph nodes via STING, down-regulating the colonic M1/M2 and splenic Th1/Th2 cell ratios, thereby improving the imbalanced immune homeostasis in the inflamed intestine. Meanwhile, based on the 16SrDNA sequencing of mice fecal samples, STING was found to facilitate the donor strain colonization in recipients' gut, mainly Lactobacillales, thereby reshaping the gut microbiota disturbed by colitis. Consequently, we proposed that STING, as a key target of FMT therapy, is potentially a biomarker for screening the most suitable individuals for FMT to optimize treatment regimens and enhance clinical benefit.}, }
@article {pmid39323880, year = {2024}, author = {Deng, L and Guo, X and Chen, J and Li, B and Liu, N and Xia, J and Ou, M and Hong, Z}, title = {Effect of intestinal microbiota transplantation on chronic hepatitis B virus infection associated liver disease.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1458754}, pmid = {39323880}, issn = {1664-302X}, abstract = {BACKGROUND: Research on the effects of intestinal microbiota transplantation (IMT) on chronic HBV infection (CHB) progression associated liver disease (HBV-CLD) and alterations in the microbiota post-IMT are quite limited for the moment.<br><br>METHODS: By integrating microbiome with metabolome analyses, we aimed to the function of IMT and the alterations of gut microbiota in patients with HBV-CLD. First, this study included 20 patients with HBV-CLD and ten healthy controls. Then, 16 patients with CHB were given IMT with donor feces (heterologous) via oral capsule. Fecal samples from CHB patients were obtained before and after IMT, as well as healthy controls, for 16S rDNA sequencing and untargeted metabolomics analysis.<br><br>RESULTS: The proalbuminemia were significantly increased after IMT, and the HBsAg and TBA showed a significant decrease after IMT in the HBV-CLD patients. There was statistical difference in the Chaol indexes between between CHB patients and healthy controls, suggesting a lower abundance of the gut microbiota in HBV-CLD patients. In addition, there was statistical difference in the Shannon and Simpson indexes between prior to IMT and post-IMT, indicating that the impaired abundance of the gut microbiota had been improved after IMT. The host-microbiota-metabolite interplay, amino acid metabolism, nicotinate and nicotinamide metabolism, starch and sucrose metabolism, steroid biosynthesis, and vitamins metabolism, were significantly lower in HBV-CLD patients than healthy controls.<br><br>CONCLUSION: IMT may improve the therapeutic effects on patients HBV-CLD. Furthermore, IMT appears to improve amino acid metabolism by impaired abundance of the gut microbiota and therefore improve liver prealbumin synthesis.}, }
@article {pmid39323631, year = {2024}, author = {Zhang, D and Cheng, H and Wu, J and Zhou, Y and Tang, F and Liu, J and Feng, W and Peng, C}, title = {The energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1392385}, pmid = {39323631}, issn = {1663-9812}, abstract = {INTRODUCTION: As a widely used traditional Chinese medicine with hot property, aconite can significantly promote energy metabolism. However, it is unclear whether the gut microbiota and bile acids contribute to the energy metabolism-promoting properties of aconite. The aim of this experiment was to verify whether the energy metabolism-promoting effect of aconite aqueous extract (AA) is related to gut microbiota and bile acid (BA) metabolism.<br><br>METHODS: The effect of AA on energy metabolism in rats was detected based on body weight, body temperature, and adipose tissue by HE staining and immunohistochemistry. In addition, 16S rRNA high-throughput sequencing and targeted metabolomics were used to detect changes in gut microbiota and BA concentrations, respectively. Antibiotic treatment and fecal microbiota transplantation (FMT) were also performed to demonstrate the importance of gut microbiota.<br><br>RESULTS: Rats given AA experienced an increase in body temperature, a decrease in body weight, and an increase in BAT (brown adipose tissue) activity and browning of WAT (white adipose tissue). Sequencing analysis and targeted metabolomics indicated that AA modulated gut microbiota and BA metabolism. The energy metabolism promotion of AA was found to be mediated by gut microbiota, as demonstrated through antibiotic treatment and FMT. Moreover, the energy metabolism-promoting effect of aconite is associated with the bile acid receptor TGR5 (Takeda G-protein-coupled receptor 5)-UCP1 (uncoupling protein 1) signaling pathway.<br><br>CONCLUSION: The energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling.}, }
@article {pmid39322832, year = {2025}, author = {Zeng, X and Ma, C and Fu, W and Xu, Y and Wang, R and Liu, D and Zhang, L and Hu, N and Li, D and Li, W}, title = {Changes in Type 1 Diabetes-Associated Gut Microbiota Aggravate Brain Ischemia Injury by Affecting Microglial Polarization Via the Butyrate-MyD88 Pathway in Mice.}, journal = {Molecular neurobiology}, volume = {62}, number = {3}, pages = {3764-3780}, pmid = {39322832}, issn = {1559-1182}, support = {81701288//National Natural Science Foundation of China/ ; YQJH2023028//Program for Young Talents of Basic Research in Universities of Heilongjiang Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Myeloid Differentiation Factor 88/metabolism ; *Butyrates/metabolism/pharmacology ; *Brain Ischemia/metabolism/microbiology/pathology/complications ; *Microglia/metabolism/pathology/drug effects ; *Diabetes Mellitus, Type 1/microbiology/complications/metabolism ; Mice, Inbred C57BL ; Male ; Mice ; *Signal Transduction/drug effects ; *Cell Polarity/drug effects ; }, abstract = {People with type 1 diabetes (T1D) have a significantly elevated risk of stroke, but the mechanism through which T1D worsens ischemic stroke remains unclear. This study was aimed at investigating the roles of T1D-associated changes in the gut microbiota in aggravating ischemic stroke and the underlying mechanism. Fecal 16SrRNA sequencing indicated that T1D mice and mice with transplantation of T1D mouse gut microbiota had lower relative abundance of butyric acid producers, f_Erysipelotrichaceae and g_Allobaculum, and lower content of butyric acid in feces. After middle cerebral artery occlusion (MCAO), these mice had poorer neurological outcomes and more severe inflammation, but higher expression of myeloid differentiation factor 88 (MyD88) in the ischemic penumbra; moreover, the microglia were inclined to polarize toward the pro-inflammatory type. Administration of butyrate to T1D mice in the drinking water alleviated the neurological damage after MCAO. Butyrate influenced the response and polarization of BV2 and decreased the production of inflammatory cytokines via MyD88 after oxygen-glucose deprivation/reoxygenation. Knocking down MyD88 in the brain alleviated neurological outcomes and decreased the concentrations of inflammatory cytokines in the brain after stroke in mice with transplantation of T1D mouse gut microbiota. Poor neurological outcomes and aggravated inflammatory responses of T1D mice after ischemic stroke may be partly due to differences in microglial polarization mediated by the gut microbiota-butyrate-MyD88 pathway. These findings provide new ideas and potential intervention targets for alleviating neurological damage after ischemic stroke in T1D.}, }
@article {pmid39322747, year = {2024}, author = {Zhang, SL and Wang, X and Cai, QQ and Chen, C and Zhang, ZY and Xu, YY and Yang, MX and Jia, QA and Wang, Y and Wang, ZM}, title = {Acarbose enhances the efficacy of immunotherapy against solid tumours by modulating the gut microbiota.}, journal = {Nature metabolism}, volume = {6}, number = {10}, pages = {1991-2009}, pmid = {39322747}, issn = {2522-5812}, support = {82203048//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Acarbose/therapeutic use/pharmacology ; *Immunotherapy/methods ; Female ; *CD8-Positive T-Lymphocytes/immunology ; Neoplasms/therapy/immunology ; Mice, Inbred C57BL ; Cell Line, Tumor ; Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; }, abstract = {The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8[+] T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8[+] T cell recruitment through the CXCL10-CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8[+] T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy.}, }
@article {pmid39322314, year = {2024}, author = {Van Hul, M and Cani, PD and Petitfils, C and De Vos, WM and Tilg, H and El-Omar, EM}, title = {What defines a healthy gut microbiome?.}, journal = {Gut}, volume = {73}, number = {11}, pages = {1893-1908}, pmid = {39322314}, issn = {1468-3288}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {The understanding that changes in microbiome composition can influence chronic human diseases and the efficiency of therapies has driven efforts to develop microbiota-centred therapies such as first and next generation probiotics, prebiotics and postbiotics, microbiota editing and faecal microbiota transplantation. Central to microbiome research is understanding how disease impacts microbiome composition and vice versa, yet there is a problematic issue with the term 'dysbiosis', which broadly links microbial imbalances to various chronic illnesses without precision or definition. Another significant issue in microbiome discussions is defining 'healthy individuals' to ascertain what characterises a healthy microbiome. This involves questioning who represents the healthiest segment of our population-whether it is those free from illnesses, athletes at peak performance, individuals living healthily through regular exercise and good nutrition or even elderly adults or centenarians who have been tested by time and achieved remarkable healthy longevity.This review advocates for delineating 'what defines a healthy microbiome?' by considering a broader range of factors related to human health and environmental influences on the microbiota. A healthy microbiome is undoubtedly linked to gut health. Nevertheless, it is very difficult to pinpoint a universally accepted definition of 'gut health' due to the complexities of measuring gut functionality besides the microbiota composition. We must take into account individual variabilities, the influence of diet, lifestyle, host and environmental factors. Moreover, the challenge in distinguishing causation from correlation between gut microbiome and overall health is presented.The review also highlights the resource-heavy nature of comprehensive gut health assessments, which hinders their practicality and broad application. Finally, we call for continued research and a nuanced approach to better understand the intricate and evolving concept of gut health, emphasising the need for more precise and inclusive definitions and methodologies in studying the microbiome.}, }
@article {pmid39321881, year = {2024}, author = {Bano, N and Khan, S and Ahamad, S and Kanshana, JS and Dar, NJ and Khan, S and Nazir, A and Bhat, SA}, title = {Microglia and gut microbiota: A double-edged sword in Alzheimer's disease.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102515}, doi = {10.1016/j.arr.2024.102515}, pmid = {39321881}, issn = {1872-9649}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Alzheimer Disease/microbiology/metabolism ; *Microglia/immunology/metabolism/microbiology ; Animals ; *Brain-Gut Axis/physiology ; *Dysbiosis/microbiology ; Neuroinflammatory Diseases/microbiology/immunology ; Brain/metabolism ; }, abstract = {The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration.}, }
@article {pmid39321863, year = {2024}, author = {Liang, J and Xiong, Z and Lei, Q and Jiang, Z and Wei, J and Ouyang, F and Chen, Y and Zeng, J}, title = {Sleep dysfunction and gut dysbiosis related amino acids metabolism disorders in cynomolgus monkeys after middle cerebral artery occlusion.}, journal = {Experimental neurology}, volume = {382}, number = {}, pages = {114970}, doi = {10.1016/j.expneurol.2024.114970}, pmid = {39321863}, issn = {1090-2430}, mesh = {Animals ; *Macaca fascicularis ; Male ; *Dysbiosis ; *Gastrointestinal Microbiome/physiology ; *Infarction, Middle Cerebral Artery/complications/cerebrospinal fluid ; *Sleep Wake Disorders/etiology/cerebrospinal fluid/metabolism ; Fecal Microbiota Transplantation/methods ; gamma-Aminobutyric Acid/cerebrospinal fluid/metabolism ; Amino Acids/cerebrospinal fluid/metabolism ; Glutamine/metabolism/cerebrospinal fluid ; }, abstract = {INTRODUCTION: This study aimed to explore the characteristics of post-stroke sleep dysfunction and verify their association with gut dysbiosis and the related amino acid metabolism disorders. This was achieved by using fecal microbiota transplantation (FMT) in a non-human primate stroke model.<br><br>METHODS: Twenty adult male cynomolgus monkeys were divided into the sham (n&#xa0;=&#xa0;4), middle cerebral artery occlusion (MCAO, n&#xa0;=&#xa0;5), MCAO + FMT (n&#xa0;=&#xa0;3), and donor (n&#xa0;=&#xa0;8) groups. The MCAO+FMT group received FMT at post-MCAO week 4. Sleep parameters, gut microbiota, gamma-aminobutyric acid (GABA), and glutamine (Gln) in the cerebrospinal fluid (CSF) were measured at baseline and postoperative weeks 4, 8, and 12.<br><br>RESULTS: At postoperative weeks 4, 8, and 12, the MCAO group showed decreased sleep efficiency, measured as the percentage of sleep during the whole night (82.3&#xa0;&#xb1;&#xa0;3.2&#xa0;% vs 91.3&#xa0;&#xb1;&#xa0;2.5&#xa0;%, 79.0&#xa0;&#xb1;&#xa0;3.75&#xa0;% vs 90.8&#xa0;&#xb1;&#xa0;3.2&#xa0;%, and 69.5&#xa0;&#xb1;&#xa0;4.8&#xa0;% vs 90.5&#xa0;&#xb1;&#xa0;2.7&#xa0;%; all P&#xa0;<&#xa0;0.05), lower relative abundance of Lactobacillus (all P&#xa0;<&#xa0;0.05), and reduced GABA concentrations in the CSF (317.3&#xa0;&#xb1;&#xa0;30.6&#xa0;nmol/L vs 437.7&#xa0;&#xb1;&#xa0;25.6&#xa0;nmol/L, 303.1&#xa0;&#xb1;&#xa0;48.9&#xa0;nmol/L vs 4 40.9&#xa0;&#xb1;&#xa0;37.8&#xa0;nmol/L, and 337.9&#xa0;&#xb1;&#xa0;49.4&#xa0;nmol/L vs 457.4&#xa0;&#xb1;&#xa0;39.2&#xa0;nmol/L; all P&#xa0;<&#xa0;0.05) compared with the sham group. Sleep efficiency at post-FMT weeks 4 and 8 (84.7&#xa0;&#xb1;&#xa0;1.1&#xa0;% vs 79.0&#xa0;&#xb1;&#xa0;3.75&#xa0;%, and 84.1&#xa0;&#xb1;&#xa0;2.0&#xa0;% vs 69.5&#xa0;&#xb1;&#xa0;4.8&#xa0;%; both P&#xa0;<&#xa0;0.05) and GABA concentration in the CSF at post-FMT week 4 (403.1&#xa0;&#xb1;&#xa0;25.4&#xa0;nmol/L vs 303.1&#xa0;&#xb1;&#xa0;48.9&#xa0;nmol/L, P&#xa0;<&#xa0;0.05) was higher in the MCAO+FMT group than in the MCAO group.<br><br>CONCLUSIONS: Post-stroke sleep dysfunction in monkeys is characterized by impaired sleep coherence, associated with decreased levels of probiotics such as Lactobacillus, GABA, and Gln in the CSF and can be ameliorated using FMT.}, }
@article {pmid39321508, year = {2024}, author = {Phanchana, M and Pipatthana, M and Phetruen, T and Konpetch, P and Prangthip, P and Harnvoravongchai, P and Sripong, C and Singhakaew, S and Wongphayak, S and Chankhamhaengdecha, S and Janvilisri, T}, title = {Identification and preclinical evaluation of MMV676558 as a promising therapeutic candidate against Clostridioides difficile.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {180}, number = {}, pages = {117469}, doi = {10.1016/j.biopha.2024.117469}, pmid = {39321508}, issn = {1950-6007}, mesh = {*Clostridioides difficile/drug effects ; Animals ; *Microbial Sensitivity Tests ; *Anti-Bacterial Agents/pharmacology ; Mice ; *Biofilms/drug effects ; Clostridium Infections/drug therapy/microbiology ; Gastrointestinal Microbiome/drug effects ; Female ; }, abstract = {Clostridioides difficile, a gram-positive, toxin-producing, spore-forming anaerobe, is a major cause of antibiotic-associated diarrhoea. The bacterium's intrinsic drug resistance limits current treatment options to fidaxomicin and vancomycin for initial episodes, with anti-toxin B monoclonal antibody or faecal microbiota transplantation recommended for complicated or recurrent cases. This underscores the urgent need for novel therapeutics. In this study, we screened the MMV Pathogen Box at a 10 µM concentration against C. difficile R20291. Primary hits were evaluated for minimum inhibitory concentrations (MIC), killing kinetics, and biofilm inhibition. Bacterial cytological profiling (BCP) and transmission electron microscopy (TEM) were employed to study the mode of action. MMV676558 was further tested in a mouse model to assess survival, histopathology, and gut microbiota effects. We identified nineteen hits that inhibited over 50 % of C. difficile growth. MIC assays revealed three hits with MICs below 16 µg/mL: MMV676558, MMV688755, and MMV690027. These hits were effective against various C. difficile ribotypes. Killing kinetics were comparable or superior to vancomycin and fidaxomicin, and biofilm assays showed inhibitory effects. BCP and TEM analyses suggested membrane function disruption as the mode of action. Furthermore, MMV676558 demonstrated a protective effect in mice, with favourable histopathology and gut microbiota profiles. Given the urgent threat posed by C. difficile antibiotic resistance, discovering new treatments is a top priority. Our study identified three promising hits from the MMV Pathogen Box, with MMV676558 showing significant in vivo potential for further evaluation.}, }
@article {pmid39320321, year = {2024}, author = {Berry, P and Khanna, S}, title = {Fecal microbiota spores, live-brpk (VOWST™/VOS) for prevention of recurrent Clostridioides difficile infection.}, journal = {Future microbiology}, volume = {19}, number = {18}, pages = {1519-1528}, doi = {10.1080/17460913.2024.2403892}, pmid = {39320321}, issn = {1746-0921}, mesh = {Humans ; *Clostridium Infections/prevention &amp; control/microbiology ; *Fecal Microbiota Transplantation ; *Clostridioides difficile ; *Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; Spores, Bacterial/drug effects ; Dysbiosis/prevention &amp; control/microbiology ; Recurrence ; Animals ; Secondary Prevention/methods ; }, abstract = {Clostridioides difficile infection (CDI) is a health crisis comprising a majority of healthcare-associated infections and is now being seen in the community. Persistent dysbiosis despite treatment with standard-of-care antibiotics increases risk of recurrent infections. Fecal microbiota transplantation has been an effective way of addressing dysbiosis, but the studies have lacked standardization, which makes outcome and safety data difficult to interpret. Standardized microbiome therapies have demonstrated efficacy and safety for recurrent CDI and have been approved to prevent recurrent infection. In this review, we discuss the data behind and the practice use of fecal microbiota spores, live-brpk (VOWST™ / VOS), a US FDA approved live biotherapeutic for the prevention of recurrent CDI.}, }
@article {pmid39320101, year = {2024}, author = {Xue, H and Wang, Y and Mei, C and Han, L and Lu, M and Li, X and Chen, T and Wang, F and Tang, X}, title = {Gut microbiome and serum metabolome alterations associated with lactose intolerance (LI): a case‒control study and paired-sample study based on the American Gut Project (AGP).}, journal = {mSystems}, volume = {9}, number = {10}, pages = {e0083924}, pmid = {39320101}, issn = {2379-5077}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Male ; Case-Control Studies ; *Metabolome ; Humans ; *Lactose Intolerance/microbiology ; Rats ; Female ; Adult ; Fecal Microbiota Transplantation ; Rats, Sprague-Dawley ; Middle Aged ; }, abstract = {UNLABELLED: Lactose intolerance (LI) is a prevalent condition characterized by gastrointestinal symptoms that arise following lactose consumption. Recent evidence suggests that the gut microbiome may influence lactose levels in the gut. However, there is limited understanding regarding the alterations in microbiota and metabolism between individuals with LI and non-LI. This study conducted a paired-sample investigation utilizing data from the American Gut Project (AGP) and performed metagenomic and untargeted metabolomic analyses in a Chinese cohort to explore the interaction between the gut microbiome and serum metabolites. In addition, fecal microbiota transplantation (FMT) experiments were conducted to further examine the impact of the LI-associated gut microbiome on inflammatory outcomes. We identified 14 microbial genera that significantly differed between LI and controls from AGP data. Using a machine learning approach, group separation was predicted based on seven species and nine metabolites in the Chinese cohort. Notably, increased levels of Escherichia coli in the LI group were negatively correlated with several metabolites, including PC (22:6/0:0), indole, and Lyso PC, while reduced levels of Faecalibacterium prausnitzii and Eubacterium rectale were positively correlated with indole and furazolidone. FMT-LI rats displayed visceral hypersensitivity and an altered gut microbiota composition compared to FMT-HC rats. Metagenomic and metabolomic analyses revealed an enrichment of MAPK signaling in LI, which was confirmed by FMT-LI rats showing higher expression of ERK and RAS, along with increased concentrations of proinflammatory cytokines. This study provides valuable insights into the disrupted microbial and metabolic traits associated with LI, emphasizing potential microbiome-based approaches for its prevention and treatment.<br><br>IMPORTANCE: Lactose intolerance (LI) is a prevalent condition characterized by gastrointestinal symptoms after lactose consumption due to a deficiency of lactase. There is limited understanding regarding the microbiota and metabolic alterations between individuals with LI and non-LI. This study represents the first exploration to investigate metagenomic and metabolomic signatures among subjects with lactose intolerance as far as our knowledge. We identified 14 microbial genera in the Western cohort and 7 microbial species, along with 9 circulating metabolites in the Chinese cohort, which significantly differed in LI patients. Metagenomic and metabolomic analyses revealed an enrichment of MAPK signaling in LI patients. This finding was confirmed by FMT-LI rats, exhibiting increased expression of ERK and RAS, along with higher concentrations of pro-inflammatory cytokines. Our study provides insights into the disrupted functional and metabolic traits of the gut microbiome in LI, highlighting potential microbiome-based approaches for preventing and treating LI.}, }
@article {pmid39318889, year = {2024}, author = {McGrath, E and Herson, MR and Kuehnert, MJ and Moniz, K and Szczepiorkowski, ZM and Pruett, TL}, title = {A WHO remit to improve global standards for medical products of human origin.}, journal = {Bulletin of the World Health Organization}, volume = {102}, number = {10}, pages = {707-714}, pmid = {39318889}, issn = {1564-0604}, mesh = {Humans ; *World Health Organization ; Global Health ; International Cooperation ; Biological Products/standards ; }, abstract = {In recent decades, considerable advances have been made in assuring the safety of blood transfusion and organ transplantation. However, with the increasing movement of medical products of human origin across international boundaries, there is a need to enhance global norms and governance. These products, which include blood, organs, tissues, cells, human milk and faecal microbiota, are today crucial for health care but they also pose unique risks due to their human origin, such as disease transmission and graft failure. Moreover, the demand for medical products of human origin often exceeds supply, leading to dependence on international supply chains, and emerging technologies like cell and gene therapy present further challenges because of their unproven efficacy and long-term risks. Current regulatory mechanisms, especially in low- and middle-income countries, are insufficient. The World Health Organization (WHO) has both the mandate and experience to lead the development of international quality and safety standards, consistent product nomenclature, and robust traceability and biovigilance systems. An international, multistakeholder approach is critical for addressing the complexities of how medical products of human origin are used globally and for ensuring their safety. This approach will require promoting uniform product descriptions, enhancing digital communication systems and leveraging existing resources to support countries in establishing regulations for these products. As illustrated by World Health Assembly resolution WHA77.4 on transplantation in 2024, WHO's ongoing efforts to ensure the safe, efficient and ethical use of medical products of human origin worldwide provide the opportunity to galvanize international cooperation on establishing norms.}, }
@article {pmid39317918, year = {2024}, author = {Ahmadi, S and Hasani, A and Khabbaz, A and Poortahmasbe, V and Hosseini, S and Yasdchi, M and Mehdizadehfar, E and Mousavi, Z and Hasani, R and Nabizadeh, E and Nezhadi, J}, title = {Dysbiosis and fecal microbiota transplant: Contemplating progress in health, neurodegeneration and longevity.}, journal = {Biogerontology}, volume = {25}, number = {6}, pages = {957-983}, pmid = {39317918}, issn = {1573-6768}, mesh = {Humans ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; *Longevity ; *Gastrointestinal Microbiome ; Neurodegenerative Diseases/microbiology/therapy ; Animals ; Aging/physiology ; Brain-Gut Axis/physiology ; }, abstract = {The gut-brain axis plays an important role in mental health. The intestinal epithelial surface is colonized by billions of commensal and transitory bacteria, known as the Gut Microbiota (GM). However, potential pathogens continuously stimulate intestinal immunity when they find the place. The last two decades have witnessed several studies revealing intestinal bacteria as a key factor in the health-disease balance of the gut, as well as disease-emergent in other parts of the body. Various neurological processes, such as cognition, learning, and memory, could be affected by dysbiosis in GM. Additionally, the aging process and longevity are related to systemic inflammation caused by dysbiosis. Commensal GM affects brain development, behavior, and healthy aging suggesting that building changes in GM might be a potential therapeutic method. The innovation in GM dysbiosis is intervention by Fecal Microbiota Transplantation (FMT), which has been confirmed as a therapy for recurrent Clostridium difficile infections and is promising for other clinical disorders, such as Parkinson's disease, Multiple Sclerosis (MS), Alzheimer's disease, and depression. Additionally, FMT may be possible to promote healthy aging, and extend longevity. This review aims to connect dysbiosis, neurological disorders, and aging and the potential of FMT as a therapeutic strategy to treat these disorders, and to enhance the quality of life in the elderly.}, }
@article {pmid39316685, year = {2024}, author = {Ke, S and Gálvez, JAV and Sun, Z and Cao, Y and Pollock, NR and Chen, X and Kelly, CP and Liu, YY}, title = {Rational Design of Live Biotherapeutic Products for the Prevention of Clostridioides difficile Infection.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiae470}, pmid = {39316685}, issn = {1537-6613}, abstract = {Clostridioides difficile infection (CDI) is a major cause of healthcare- and antibiotic-associated diarrhea. While fecal microbiota transplantation (FMT) shows promise for recurrent CDI, its mechanisms and long-term safety are not fully understood. Live biotherapeutic products (LBPs) using pre-defined bacterial consortia offer an alternative option, but the rational designing LBPs remains challenging. Here, we employ a computational pipeline and three metagenomic datasets to identify microbial strains for LBPs targeting CDI. We constructed the CDI-related microbial genome catalog, comprising 3,741 non-redundant metagenome-assembled genomes (nrMAGs) and identified multiple potential protective nrMAGs, including strains from Dorea formicigenerans, Oscillibacter welbionis, and Faecalibacterium prausnitzii. Importantly, some of these protective nrMAGs were found to play an important role in FMT success, and most top protective nrMAGs can be validated by various previous findings. Our results demonstrate a framework for selecting microbial strains targeting CDI, paving the way for the computational design of LBPs against other enteric infections.}, }
@article {pmid39315788, year = {2024}, author = {Wang, Y and Bing, H and Jiang, C and Wang, J and Wang, X and Xia, Z and Chu, Q}, title = {Gut microbiota dysbiosis and neurological function recovery after intracerebral hemorrhage: an analysis of clinical samples.}, journal = {Microbiology spectrum}, volume = {12}, number = {11}, pages = {e0117824}, pmid = {39315788}, issn = {2165-0497}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Cerebral Hemorrhage/microbiology ; Male ; *Dysbiosis/microbiology ; Female ; Middle Aged ; Aged ; *Bacteria/classification/isolation &amp; purification/genetics ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Prognosis ; Recovery of Function ; Adult ; }, abstract = {We aimed to investigate the microbial community composition in patients with intracerebral hemorrhage (ICH) and its effect on prognosis. We designed two clinical cohort studies to explore the gut dysbiosis after ICH and their relationship with neurological function prognosis. First, fecal samples from patients with ICH at three time points: T1 (within 24 h of admission), T2 (3 days after surgery), and T3 (7 days after surgery), and healthy volunteers were subjected to 16S rRNA sequencing using Illumina high-throughput sequencing technology. When differential gut microbiota was identified, the correlation between clinical indicators and microbiotas was analyzed. Subsequently, the patients with ICH were categorized into GOOD and POOR groups based on their Glasgow Outcome Scale Extended (GOS-E) score, and the disparities in gut microbiota between the two groups were assessed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The composition and diversity of the gut microbiota in patients with ICH were different from those in the control group and changed dynamically with the extension of the course of cerebral hemorrhage. The abundances of Enterococcaceae, Clostridiales incertae sedis XI, and Peptoniphilaceae were significantly increased in patients with ICH, whereas Bacteroidaceae, Ruminococcaceae, Lachnospiraceae, and Veillonellaceae were significantly reduced. The relative abundance of Enterococcus gradually increased with the extension of the duration of ICH after surgery, and the abundance of Bacteroides gradually decreased. The abundance of Enterococcus before surgery was found to be negatively associated with patient neurological function prognosis. The original ICH score and Lachnospiraceae status were independent risk factors for predicting the prognosis of neurological function in patients with ICH (P < 0.05). Changes in the gut microbiota diversity in patients with ICH were related to prognosis. Lachnospiraceae may have a protective effect on prognosis.IMPORTANCEAcute central nervous system injuries like hemorrhagic stroke are major global health issues. While surgical hematoma removal can alleviate brain damage, severe cases still have a high 1-month mortality rate of up to 40%. Gut microbiota significantly impacts health, and treatments like fecal microbiota transplantation (FMT) and probiotics can improve brain damage by correcting gut microbiota imbalances caused by ischemic stroke. However, few clinical studies have explored this relationship in hemorrhagic stroke. This study investigated the impact of cerebral hemorrhage on the composition of gut microbiota, and we found that Lachnospiraceae were the independent risk factors for poor prognosis in intracerebral hemorrhage (ICH). The findings offer potential insights for the application of FMT in patients with ICH, and it may improve the prognosis of patients.}, }
@article {pmid39315776, year = {2024}, author = {Li, S and Liu, M and Han, Y and Liu, C and Cao, S and Cui, Y and Zhu, X and Wang, Z and Liu, B and Shi, Y}, title = {Gut microbiota-derived gamma-aminobutyric acid improves host appetite by inhibiting satiety hormone secretion.}, journal = {mSystems}, volume = {9}, number = {10}, pages = {e0101524}, pmid = {39315776}, issn = {2379-5077}, support = {No. 244200510010//Science and technology innovation leading talent in central plains/ ; No. 22IRTSTHN022//Science and Technology Innovation Team of Henan Province High Quality Forage and Animal Health/ ; No. CARS-34//China Agricultural Research System (CARS)/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; Rabbits ; *Appetite/drug effects ; *gamma-Aminobutyric Acid/metabolism ; *Fecal Microbiota Transplantation ; Male ; RNA, Ribosomal, 16S/genetics ; Feeding Behavior/drug effects ; }, abstract = {Globally, appetite disorders have become an increasingly prominent public health issue. While short-term appetite loss may seem relatively harmless, prolonged instances can lead to serious physical and mental damage. In recent years, numerous studies have highlighted the significant role of the "microbiota-gut-brain" axis in the regulation of feeding behavior in organisms, suggesting that targeting the gut microbiota may be a novel therapeutic strategy for appetite disorders. However, the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between the two remain unclear. Based on this, we conducted 16S rRNA sequencing to analyze the gut microbiota of rabbits with high and low feed intake, followed by fecal microbiota transplantation (FMT) and metabolite gavage experiments to elucidate the underlying mechanisms. Our research indicates that the high feed intake group exhibited significant enrichment of the g__Bacteroides and gamma-aminobutyric acid (GABA), and intragastric administration of GABA effectively promoted the host's feeding behavior. The underlying mechanism involves GABA derived from the gut microbiota inhibiting the secretion of satiety hormones to enhance the host's feeding behavior. Furthermore, the results of FMT suggest that differences in gut microbiota composition may be a contributing factor to varying levels of feed intake in the host. In conclusion, these findings emphasize the role of the gut microbiota-derived GABA, in increasing host feed intake, offering a new target for the treatment of appetite disorders from the perspective of gut microbiota.IMPORTANCEThe incidence of anorexia is rapidly increasing and has become a global burden. Gut microbiota can participate in the regulation of host feeding behavior, yet the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between them remain unclear. In this study, we utilized 16S rRNA sequencing to investigate the composition of the gut microbiota in rabbits with varying levels of feed intake and employed fecal microbiota transplantation and gastric infusion experiments with gamma-aminobutyric acid (GABA) to elucidate the potential mechanisms involved. GABA derived from the gut microbiota can effectively enhance the host's feeding behavior by inhibiting the secretion of satiety hormones. This discovery underscores the pivotal role of the gut microbiota in modulating host appetite, offering novel research avenues and therapeutic targets for appetite disorders.}, }
@article {pmid39315595, year = {2024}, author = {Sun, B and Wang, Y and Bai, J and Li, X and Ma, L and Man, S}, title = {Litchi Procyanidins Ameliorate DSS-Induced Colitis through Gut Microbiota-Dependent Regulation of Treg/Th17 Balance.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {44}, pages = {24823-24832}, doi = {10.1021/acs.jafc.4c05577}, pmid = {39315595}, issn = {1520-5118}, mesh = {Animals ; *Th17 Cells/immunology/drug effects ; *Proanthocyanidins/pharmacology/administration &amp; dosage ; *Gastrointestinal Microbiome/drug effects ; *T-Lymphocytes, Regulatory/immunology/drug effects ; Mice ; *Dextran Sulfate/adverse effects ; *Mice, Inbred C57BL ; Male ; Humans ; *Plant Extracts/administration &amp; dosage/pharmacology ; *Colitis/chemically induced/drug therapy/immunology ; *Litchi/chemistry ; Bacteria/classification/isolation &amp; purification/genetics/drug effects ; Biflavonoids/pharmacology/administration &amp; dosage ; Colitis, Ulcerative/drug therapy/immunology/chemically induced/microbiology ; Catechin/administration &amp; dosage/pharmacology ; }, abstract = {Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-β, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota, Oscillospiraceae, Muribaculaceae, and Desulfovibrionaceae, as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC's effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.}, }
@article {pmid39315196, year = {2024}, author = {Luo, C and Yang, Y and Jiang, C and Lv, A and Zuo, W and Ye, Y and Ke, J}, title = {Influenza and the gut microbiota: A hidden therapeutic link.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37661}, pmid = {39315196}, issn = {2405-8440}, abstract = {BACKGROUND: The extensive community of gut microbiota significantly influences various biological functions throughout the body, making its characterization a focal point in biomedicine research. Over the past few decades, studies have revealed a potential link between specific gut bacteria, their associated metabolic pathways, and influenza. Bacterial metabolites can communicate directly or indirectly with organs beyond the gut via the intestinal barrier, thereby impacting the physiological functions of the host. As the microbiota increasingly emerges as a 'gut signature' in influenza, gaining a deeper understanding of its role may offer new insights into its pathophysiological relevance and open avenues for novel therapeutic targets. In this Review, we explore the differences in gut microbiota between healthy individuals and those with influenza, the relationship between gut microbiota metabolites and influenza, and potential strategies for preventing and treating influenza through the regulation of gut microbiota and its metabolites, including fecal microbiota transplantation and microecological preparations.<br><br>METHODS: We utilized PubMed and Web of Science as our search databases, employing keywords such as "influenza," "gut microbiota," "traditional Chinese medicine," "metabolites," "prebiotics," "probiotics," and "machine learning" to retrieve studies examining the potential therapeutic connections between the modulation of gut microbiota and its metabolites in the treatment of influenza. The search encompassed literature from the inception of the databases up to December 2023.<br><br>RESULTS: Fecal microbiota transplantation (FMT), microbial preparations (probiotics and prebiotics), and traditional Chinese medicine have unique advantages in regulating intestinal microbiota and its metabolites to improve influenza outcomes. The primary mechanism involves increasing beneficial intestinal bacteria such as Bacteroidetes and Bifidobacterium while reducing harmful bacteria such as Proteobacteria. These interventions act directly or indirectly on metabolites such as short-chain fatty acids (SCFAs), amino acids (AAs), bile acids, and monoamines to alleviate lung inflammation, reduce viral load, and exert anti-influenza virus effects.<br><br>CONCLUSION: The gut microbiota and its metabolites have direct or indirect therapeutic effects on influenza, presenting broad research potential for providing new directions in influenza research and offering references for clinical prevention and treatment. Future research should focus on identifying key strains, specific metabolites, and immune regulation mechanisms within the gut microbiota to accurately target microbiota interventions and prevent respiratory viral infections such as influenza.}, }
@article {pmid39314882, year = {2024}, author = {Larsen, OFA and Brummer, RJM}, title = {Perspective: on the future of fecal microbiota transplantation.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1449133}, pmid = {39314882}, issn = {1664-302X}, abstract = {Fecal Microbiota Transplantation (FMT) has shown to possess impressive potential benefit for a wide range of clinical indications. Due to its inherent safety issues and efficacy constraints, the use of personalized FMT analogs could be a promising avenue. The development of such analogs will require a detailed understanding of their functionality, encompassing not only microbe-host interactions of the microbial taxa that are involved, but also of the ecological dimensions of the analogs and an overview of the gastrointestinal sites where these relevant microbial interactions take place. Moreover, characterization of taxa that have been lost due to diminished exposure to beneficial microbes, as a consequence of Western lifestyle, may lead to creation of future FMT analogs with the capacity to restore functionalities that we have lost.}, }
@article {pmid39314425, year = {2024}, author = {de Araujo, A and Sree Kumar, H and Yang, T and Plata, AA and Dirr, EW and Bearss, N and Baekey, DM and Miller, DS and Donertas-Ayaz, B and Ahmari, N and Singh, A and Kalinoski, AL and Garrett, TJ and Martyniuk, CJ and de Lartigue, G and Zubcevic, J}, title = {Intestinal serotonergic vagal signaling as a mediator of microbiota-induced hypertension.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.07.17.603451}, pmid = {39314425}, issn = {2692-8205}, abstract = {Hypertension is a pervasive global health challenge, impacting over a billion individuals worldwide. Despite strides in therapeutic strategies, a significant proportion of patients remain resistant to the currently available therapies. While conventional treatments predominantly focus on cardiac, renal, and cerebral targets, emerging research underscores the pivotal role of the gut and its microbiota. Yet, the precise mechanisms governing interactions between the gut microbiota and the host blood pressure remain unclear. Here we describe a neural host-microbiota interaction that is mediated by the intestinal serotonin (5-HT) signaling via vagal 5HT3a receptors and which is crucial for maintenance of blood pressure homeostasis. Notably, a marked decrease in both intestinal 5-HT and vagal 5HT3aR signaling is observed in hypertensive rats, and in rats subjected to fecal microbiota transplantation from hypertensive rats. Leveraging an intersectional genetic strategy in a Cre rat line, we demonstrate that intestinal 5HT3aR vagal signaling is a crucial link between the gut microbiota and blood pressure homeostasis and that recovery of 5-HT signaling in colon innervating vagal neurons can alleviate hypertension. This paradigm-shifting finding enhances our comprehension of hypertensive pathophysiology and unveils a promising new therapeutic target for combating resistant hypertension associated with gut dysbiosis.}, }
@article {pmid39311394, year = {2024}, author = {Ben Salem, I and Khemiri, H and Drechsel, O and Arbi, M and Böttcher, S and Mekki, N and Ben Fraj, I and Souiai, O and Yahyaoui, M and Ben Farhat, E and Meddeb, Z and Touzi, H and Ben Mustapha, I and BenKahla, A and Ouederni, M and Barbouche, MR and Diedrich, S and Triki, H and Haddad-Boubaker, S}, title = {Reversion of neurovirulent mutations, recombination and high intra-host diversity in vaccine-derived poliovirus excreted by patients with primary immune deficiency.}, journal = {Journal of medical virology}, volume = {96}, number = {9}, pages = {e29918}, doi = {10.1002/jmv.29918}, pmid = {39311394}, issn = {1096-9071}, support = {811034//European project PHINDaccess: Strengthening Omics data analysis capacities in pathogen-host interaction/ ; LR20IPT10//Tunisian Ministry of Higher Education and Scientifc Research/ ; }, mesh = {Humans ; *Poliovirus/genetics/classification/isolation &amp; purification/immunology ; *Poliovirus Vaccine, Oral/genetics/adverse effects ; *Recombination, Genetic ; *Mutation ; *Poliomyelitis/virology/prevention &amp; control ; *Feces/virology ; Male ; Female ; *Virus Shedding ; Genome, Viral/genetics ; Genetic Variation ; Primary Immunodeficiency Diseases/genetics ; Child, Preschool ; Evolution, Molecular ; Child ; Infant ; Virulence/genetics ; Phylogeny ; }, abstract = {Patients with Primary immunodeficiency (PIDs) may be infected by Polioviruses (PVs), especially when vaccinated with live Oral Polio Vaccine before diagnosis. They may establish long-term shedding of divergent strains and may act as reservoirs of PV transmission. This study delved into the effect of the genetic evolution of complete PV genomes, from MHC class II-deficient patients, on the excretion duration and clinical outcomes. Stool samples from three PID patients underwent analysis for PV detection through inoculation on cell culture and real-time PCR, followed by VP1 partial sequencing and full genome sequencing using the Illumina technology. Our findings revealed a low number of mutations for one patient who cleared the virus, while two exhibited a high intra-host diversity favoring the establishment of severe outcomes. Neurovirulence-reverse mutations were detected in two patients, possibly leading to paralysis development. Furthermore, a recombination event, between type 3 Vaccine-Derived Poliovirus and Sabin-like1 (VDPV3/SL1), occurred in one patient. Our findings have suggested an association between intra-host diversity, recombination, prolonged excretion of the virus, and emergence of highly pathogenic strains. Further studies on intra-host diversity are crucial for a better understanding of the virus evolution as well as for the success of the Global Polio Eradication Initiative.}, }
@article {pmid39309854, year = {2024}, author = {Wu, M and Chen, X and Lu, Q and Yao, X}, title = {Fecal microbiota transplantation for the treatment of chronic inflammatory skin diseases.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37432}, pmid = {39309854}, issn = {2405-8440}, abstract = {The regulation of immune functions and the maintenance of homeostasis in the internal environment are both integral to human gut microbiota (GM). If GM is disturbed, it can result in a range of autoimmune diseases, including chronic inflammatory skin conditions. Chronic inflammatory skin diseases driven by T or B-cell-mediated immune reactions are complex, including the most prevalent diseases and some rare diseases. Expanding knowledge of GM dysbiosis in chronic inflammatory skin diseases has emerged. The GM has some causal roles in the pathogenesis of these skin conditions. Targeting microbiota treatment, particularly fecal microbiota transplantation (FMT), is considered to be a promising strategy. FMT was commonly used in intestinal diseases by reshaping and balancing GM, serving as a reasonable administration in these skin inflammatory diseases. This paper summarizes the existing knowledge of GM dysbiosis in chronic inflammatory skin diseases and the research data on FMT treatment for such conditions.}, }
@article {pmid39306158, year = {2024}, author = {Peng, G and Wang, S and Zhang, H and Xie, F and Jiao, L and Yuan, Y and Ma, C and Wu, H and Meng, Z}, title = {Tremella aurantialba polysaccharides alleviate ulcerative colitis in mice by improving intestinal barrier via modulating gut microbiota and inhibiting ferroptosis.}, journal = {International journal of biological macromolecules}, volume = {281}, number = {Pt 4}, pages = {135835}, doi = {10.1016/j.ijbiomac.2024.135835}, pmid = {39306158}, issn = {1879-0003}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/chemically induced/metabolism ; *Ferroptosis/drug effects ; *Gastrointestinal Microbiome/drug effects ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/drug effects/metabolism/microbiology/pathology ; Basidiomycota/chemistry ; Male ; Dextran Sulfate ; Fungal Polysaccharides/pharmacology/chemistry ; Polysaccharides/pharmacology/chemistry ; Disease Models, Animal ; Lipid Peroxidation/drug effects ; }, abstract = {We aimed to investigate the effect of a polysaccharide from Tremella aurantialba on ulcerative colitis (UC), which targets ferroptosis in epithelial cells. TA 2-1 (127 kDa) was isolated from T. aurantialba and consisted of Man, Xyl, GlcA, Glc, Fuc and Rha with a molar ratio of 59.2: 23.2: 13.9: 1.6: 1.7: 0.4, exhibited a 1, 3-Man structure with branch chains of T-Xylp, 1,3-Xylp, 1,4-GlcAp, and T-Manp at its O-2 position. TA 2-1 (100 μg/mL) inhibited the cell viability of ferroptosis (19.8 %) in RLS3-induced Caco-2 cells and significantly ameliorated symptoms in the colons of mice with dextran sodium sulfate (DSS)-induced UC. TA 2-1 remarkably repaired the intestinal barrier by upregulating claudin-1 and zonula occludens-1 levels. Further analysis found TA 2-1 significantly suppressed lipid peroxidation by regulating ferroptosis-related proteins in UC mice, suggesting that its protective effects are partially mediated by inhibiting ferroptosis. Further analysis of the gut microbiota and fecal microbiota transplantation revealed TA 2-1 might relieve UC symptoms or inhibit ferroptosis by modulating the gut microbiota's composition or metabolites. Results suggest the protective effects of TA 2-1 on the intestinal barrier by inhibiting ferroptosis of epithelial cells, at least by regulating the gut microbiota, highlighting the potential of TA 2-1 in UC treatment.}, }
@article {pmid39306049, year = {2024}, author = {Shan, L and Fan, H and Guo, J and Zhou, H and Li, F and Jiang, Z and Wu, D and Feng, X and Mo, R and Liu, Y and Zhang, T and Zhou, Y}, title = {Impairment of oocyte quality caused by gut microbiota dysbiosis in obesity.}, journal = {Genomics}, volume = {116}, number = {5}, pages = {110941}, doi = {10.1016/j.ygeno.2024.110941}, pmid = {39306049}, issn = {1089-8646}, mesh = {Animals ; *Obesity/microbiology/metabolism ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; *Oocytes/metabolism ; Female ; Mice ; *Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; }, abstract = {Obesity poses risks to oocyte maturation and embryonic development in mice and humans, linked to gut microbiota dysbiosis and altered host metabolomes. However, it is unclear whether symbiotic gut microbes have a pivotal role in oocyte quality. In mouse models of fecal microbiota transplantation, we demonstrated aberrant meiotic apparatus and impaired maternal mRNA in oocytes, which is coincident with the poor developmental competence of embryos. Using metabolomics profiling, we discovered that the cytosine and cytidine metabolism was disturbed, which could account for the fertility defects observed in the high-fat diet (HFD) recipient mice. Additionally, cytosine and cytidine are closely related with gut microbiota dysbiosis, which is accompanied by a notable reduction of abundance of Christensenellaceae R-7 group in the HFD mice. In summary, our findings provided evidence that modifying the gut microbiota may be of value in the treatment of infertile female individuals with obesity.}, }
@article {pmid39305117, year = {2024}, author = {Walrath, T and Najarro, KM and Giesy, LE and Khair, S and Orlicky, DJ and McMahan, RH and Kovacs, EJ}, title = {Reducing the excessive inflammation after burn injury in aged mice by maintaining a healthier intestinal microbiome.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {38}, number = {18}, pages = {e70065}, pmid = {39305117}, issn = {1530-6860}, support = {I01BX004335//U.S. Department of Veterans Affairs (VA)/ ; R01 AG018859/AG/NIA NIH HHS/United States ; R35 GM131831/GM/NIGMS NIH HHS/United States ; T32 AG000279/AG/NIA NIH HHS/United States ; I01 BX004335/BX/BLRD VA/United States ; F32 AG082443/AG/NIA NIH HHS/United States ; T32 GM136444/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Burns/microbiology ; *Gastrointestinal Microbiome ; Mice ; *Inflammation/microbiology ; Mice, Inbred C57BL ; Male ; Aging ; Feces/microbiology ; Lung/microbiology/metabolism/pathology ; Fecal Microbiota Transplantation ; Bacteroidetes ; Ileum/microbiology/metabolism ; }, abstract = {One in six people are projected to be 65 years or older by 2050. As the population ages, better treatments for injuries that disproportionately impact the aged population will be needed. Clinical studies show that people aged 65 and older experience higher rates of morbidity and mortality after burn injury, including a greater incidence of pulmonary complications when compared to younger burn injured adults, which we and others believe is mediated, in part, by inflammation originating in the intestines. Herein, we use our clinically relevant model of scald burn injury in young and aged mice to determine whether cohousing aged mice with young mice or giving aged mice oral gavage of fecal material from young mice is sufficient to alter the microbiome of the aged mice and protect them from inflammation in the ileum and the lungs. Aged burn injured mice have less DNA expression of Bacteroidetes in the feces and an unhealthy Firmicutes/Bacteroidetes ratio. Both Bacteroidetes and the ratio of these two phyla are restored in aged burn injured by prior cohousing for a month with younger mice but not fecal transfer from young mice. This shift in the microbiome coincides with heightened expression of danger-associated molecular patterns (DAMP), and pro-inflammatory cytokine interleukin-6 (il6) in the ileum and lung of aged, burn injured mice, and heightened antimicrobial peptide camp in the lung. Cohousing reverses DAMP expression in the ileum and lung, and cathelicidin-related antimicrobial peptide protein (camp) in the lung, while fecal transfer heightened DAMPs while reducing camp in the lung, and also increased IL-6 protein in the lungs. These results highlight the importance of the intestinal microbiome in mediating inflammation within the gut-lung axis, giving insights into potential future treatments in the clinic.}, }
@article {pmid39303815, year = {2025}, author = {Xie, X and Li, W and Xiong, Z and Xu, J and Liao, T and Sun, L and Xu, H and Zhang, M and Zhou, J and Xiong, W and Fu, Z and Li, Z and Han, Q and Cui, D and Anthony, DC}, title = {Metformin reprograms tryptophan metabolism via gut microbiome-derived bile acid metabolites to ameliorate depression-Like behaviors in mice.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {442-455}, doi = {10.1016/j.bbi.2024.09.014}, pmid = {39303815}, issn = {1090-2139}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Metformin/pharmacology ; Mice ; *Bile Acids and Salts/metabolism ; *Depression/metabolism/drug therapy ; Male ; *Tryptophan/metabolism ; *Serotonin/metabolism ; *Brain/metabolism/drug effects ; Mice, Inbred C57BL ; Behavior, Animal/drug effects ; Stress, Psychological/metabolism ; Akkermansia/metabolism/drug effects ; Antidepressive Agents/pharmacology ; Disease Models, Animal ; Fecal Microbiota Transplantation/methods ; Dysbiosis/metabolism ; }, abstract = {As an adjunct therapy, metformin enhances the efficacy of conventional antidepressant medications. However, its mode of action remains unclear. Here, metformin was found to ameliorate depression-like behaviors in mice exposed to chronic restraint stress (CRS) by normalizing the dysbiotic gut microbiome. Fecal transplants from metformin-treated mice ameliorated depressive behaviors in stressed mice. Microbiome profiling revealed that Akkermansia muciniphila (A. muciniphila), in particular, was markedly increased in the gut by metformin and that oral administration of this species alone was sufficient to reverse CRS-induced depressive behaviors and normalize aberrant stress-induced 5-hydroxytryptamine (5-HT) metabolism in the brain and gut. Untargeted metabolomic profiling further identified the bile acid metabolites taurocholate and deoxycholic acid as direct A. muciniphila-derived molecules that are, individually, sufficient to rescue the CRS-induced impaired 5-HT metabolism and depression-like behaviors. Thus, we report metformin reprograms 5-HT metabolism via microbiome-brain interactions to mitigate depressive syndromes, providing novel insights into gut microbiota-derived bile acids as potential therapeutic candidates for depressive mood disorders from bench to bedside.}, }
@article {pmid39303724, year = {2024}, author = {Wang, X and Fang, Y and Liang, W and Wong, CC and Qin, H and Gao, Y and Liang, M and Song, L and Zhang, Y and Fan, M and Liu, C and Lau, HC and Xu, L and Li, X and Song, W and Wang, J and Wang, N and Yang, T and Mo, M and Zhang, X and Fang, J and Liao, B and Sung, JJY and Yu, J}, title = {Fusobacterium nucleatum facilitates anti-PD-1 therapy in microsatellite stable colorectal cancer.}, journal = {Cancer cell}, volume = {42}, number = {10}, pages = {1729-1746.e8}, doi = {10.1016/j.ccell.2024.08.019}, pmid = {39303724}, issn = {1878-3686}, mesh = {*Colorectal Neoplasms/genetics/immunology/drug therapy/therapy ; Humans ; Animals ; *Fusobacterium nucleatum ; Mice ; *Fecal Microbiota Transplantation ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; *CD8-Positive T-Lymphocytes/immunology ; T-Box Domain Proteins/genetics/metabolism ; Microsatellite Instability ; Butyric Acid/pharmacology ; Female ; Male ; Microsatellite Repeats ; }, abstract = {Microsatellite stable (MSS) colorectal cancers (CRCs) are often resistant to anti-programmed death-1 (PD-1) therapy. Here, we show that a CRC pathogen, Fusobacterium nucleatum (Fn), paradoxically sensitizes MSS CRC to anti-PD-1. Fecal microbiota transplantation (FMT) from patients with Fn-high MSS CRC to germ-free mice bearing MSS CRC confers sensitivity to anti-PD-1 compared to FMT from Fn-low counterparts. Single Fn administration also potentiates anti-PD-1 efficacy in murine allografts and CD34[+]-humanized mice bearing MSS CRC. Mechanistically, we demonstrate that intratumoral Fn generates abundant butyric acid, which inhibits histone deacetylase (HDAC) 3/8 in CD8[+] T cells, inducing Tbx21 promoter H3K27 acetylation and expression. TBX21 transcriptionally represses PD-1, alleviating CD8[+] T cell exhaustion and promoting effector function. Supporting this notion, knockout of a butyric acid-producing gene in Fn abolishes its anti-PD-1 boosting effect. In patients with MSS CRC, high intratumoral Fn predicts favorable response to anti-PD-1 therapy, indicating Fn as a potential biomarker of immunotherapy response in MSS CRC.}, }
@article {pmid39303605, year = {2024}, author = {Zhao, Y and Sokol, H and Cao, Q and Zhang, H and Yan, Y and Xie, L and Wang, H}, title = {Systemic inflammatory response to daily exposure to microcystin-LR and the underlying gut microbial mechanisms.}, journal = {Journal of hazardous materials}, volume = {480}, number = {}, pages = {135855}, doi = {10.1016/j.jhazmat.2024.135855}, pmid = {39303605}, issn = {1873-3336}, mesh = {*Microcystins/toxicity ; *Marine Toxins ; Animals ; *Gastrointestinal Microbiome/drug effects ; *Inflammation ; Mice, Inbred C57BL ; Mice ; Dysbiosis/chemically induced ; Male ; Cytokines/metabolism/blood ; RNA, Ribosomal, 16S/genetics ; Female ; Colitis/chemically induced ; Fecal Microbiota Transplantation ; }, abstract = {Cyanobacterial toxins have raised global concerns due to potential chronic disease implications from daily drinking water exposure, which remain largely unknown despite extensive research on their acute effects. To understand the mechanisms underlying microcystin-LR (MC-LR)-induced inflammation-associated diseases. Mice were exposed to MC-LR for one year at concentrations comparable to human environmental exposure levels. Comprehensive pathological observation and multi-omics approaches based on 16S rRNA gene sequencing, untargeted metabolomics, transcriptomics and proteomics were conducted across various organs. Daily exposure to MC-LR induced intestinal microbial dysbiosis and colitis-like changes. It also caused systemic chronic inflammation marked by elevated serum levels of inflammatory cytokines, inflammation-associated pathological changes, and identification of infection-related genes/proteins within the gut-brain-spleen-liver axis. Furthermore, multi-omics analysis across organs suggested that Muribaculaceae may promote a systemic infection-inflammatory response, relying on kynurenine metabolites signaling in peripheral tissues. In contrast, Lachnospiraceae may act an opposing role, dependent on intestinal indole derivatives via the neuroimmunomodulation pathway. A fecal microbiota transplantation experiment confirmed that alterations in Muribaculaceae and Lachnospiraceae resulting from exposure to MC-LR triggered the local and systemic chronic inflammation in mice. This study light on the potential strategies employed by gut microbial community in regulating MC-induced inflammation-associated chronic diseases under repeated exposure through drinking water.}, }
@article {pmid39301964, year = {2024}, author = {Bohm, MS and Ramesh, AV and Pierre, JF and Cook, KL and Murphy, EA and Makowski, L}, title = {Fecal microbial transplants as investigative tools in cancer.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {327}, number = {5}, pages = {G711-G726}, pmid = {39301964}, issn = {1522-1547}, support = {R01 CA253329/CA/NCI NIH HHS/United States ; BC210715//U.S. Department of Defense (DOD)/ ; R01 CA246809/CA/NCI NIH HHS/United States ; U01 CA272977/CA/NCI NIH HHS/United States ; R01CA246809//HHS | NIH | National Cancer Institute (NCI)/ ; U01 CA272541/CA/NCI NIH HHS/United States ; U01CA272977//HHS | NIH | National Cancer Institute (NCI)/ ; U01CA272541//HHS | NIH | National Cancer Institute (NCI)/ ; R01CA253329//HHS | NIH | National Cancer Institute (NCI)/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Neoplasms/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; Feces/microbiology ; Probiotics/therapeutic use ; }, abstract = {The gut microbiome plays a critical role in the development, progression, and treatment of cancer. As interest in microbiome-immune-cancer interactions expands, the prevalence of fecal microbial transplant (FMT) models has increased proportionally. However, current literature does not provide adequate details or consistent approaches to allow for necessary rigor and experimental reproducibility. In this review, we evaluate key studies using FMT to investigate the relationship between the gut microbiome and various types of cancer. In addition, we will discuss the common pitfalls of these experiments and methods for improved standardization and validation as the field uses FMT with greater frequency. Finally, this review focuses on the impacts of the gut and extraintestinal microbes, prebiotics, probiotics, and postbiotics in cancer risk and response to therapy across a variety of tumor types.NEW &amp; NOTEWORTHY The microbiome impacts the onset, progression, and therapy response of certain types of cancer. Fecal microbial transplants (FMTs) are an increasingly prevalent tool to test these mechanisms that require standardization by the field.}, }
@article {pmid39301264, year = {2024}, author = {Zhao, Y and Ma, S and Liang, L and Cao, S and Fan, Z and He, D and Shi, X and Zhang, Y and Liu, B and Zhai, M and Wu, S and Kuang, F and Zhang, H}, title = {Gut Microbiota-Metabolite-Brain Axis Reconstitution Reverses Sevoflurane-Induced Social and Synaptic Deficits in Neonatal Mice.}, journal = {Research (Washington, D.C.)}, volume = {7}, number = {}, pages = {0482}, pmid = {39301264}, issn = {2639-5274}, abstract = {Background: The mechanisms underlying social dysfunction caused by repeated sevoflurane in early life remain unclear. Whether the gut microbiota-metabolite-brain axis is involved in the mechanism of sevoflurane developmental neurotoxicity still lacks report. Methods: Mice received 3% sevoflurane at postnatal day (PND) 6, 7, and 8 for 2 h per day. Metagenomic sequencing and untargeted metabolomic analysis were applied to investigate the effects of sevoflurane on gut microbiota and metabolism. The animal social behavior and the synaptic development were analyzed during PND 35. Subsequently, fecal microbiota transplantation (FMT) from the control group and bile acid administration were performed to see the expected rescuing effect on socially related behaviors that were impaired by repeated sevoflurane exposure in the mice. Results: In the 3-chamber test, sevoflurane-exposed mice spent less time with stranger mice compared with the control group. The density of both the apical and basal spine decreased in mice exposed to sevoflurane. In addition, repeated sevoflurane exposure led to a notable alteration in the gut microbiota and metabolite synthesis, particularly bile acid. FMT reduced the production of intestinal bile acid and attenuated the effect of sevoflurane exposure on social function and synaptic development. Cholestyramine treatment mimics the protective effects of FMT. Conclusions: The gut microbiota-metabolite-brain axis underlies social dysfunction caused by sevoflurane exposure in early age, and bile acid regulation may be a promising intervention to this impairment.}, }
@article {pmid39302074, year = {2024}, author = {Duan, T and Alim, A and Tian, H and Li, T}, title = {Roundup-Induced Gut Dysbiosis, Irrelevant to Aromatic Amino Acid Deficiency, Impairs the Gut Function in Rats.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c04045}, pmid = {39302074}, issn = {1520-5118}, abstract = {Glyphosate, the most popular herbicide globally, has long been considered safe for mammals. However, whether glyphosate can disturb gut microbiota via inhibiting aromatic amino acid (AAA) synthesis has been under debate recently. Here, we evaluated the impacts of chronic exposure to Roundup on gut health with the addition of AAA and explored the mechanism behind Roundup-induced gut dysfunction by performing fecal microbiota transplantation. 500 mg/kg·bw of Roundup, independent of AAA deficiency, caused severe damage to gut function, as characterized by gut microbial dysbiosis, oxidative stress damage, intestinal inflammation, and histopathological injury, particularly in female rats. Notably, similar to Roundup, Roundup-shaped gut microbiome evidently damaged serum, cecum, and colon profiling of oxidative stress biomarkers (malonaldehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and H2O2). Moreover, it induced 0.65-, 3.29-, and 2.36-fold increases in colonic IL-1β, IL-6, and TNF-α levels, and 0.34-fold decreases in the IL-10 level. Upon transplanting healthy fecal microbiota to Roundup-treated rats, they exhibited a healthier gut microenvironment with mitigated inflammation, oxidative damage, and intestinal injury. Overall, our findings provide new insights into the safety of Roundup, highlight the crucial role of gut microbiota in Roundup-induced gut dysfunction, and pave the way for developing gut-microbiota-based strategies to address Roundup-related safety issues.}, }
@article {pmid39300177, year = {2024}, author = {Hunthai, S and Usawachintachit, M and Taweevisit, M and Srisa-Art, M and Anegkamol, W and Tosukhowong, P and Rattanachaisit, P and Chuaypen, N and Dissayabutra, T}, title = {Unraveling the role of gut microbiota by fecal microbiota transplantation in rat model of kidney stone disease.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {21924}, pmid = {39300177}, issn = {2045-2322}, support = {B36G660010//the Program Management Unit for Human Resources and Institutional Development, Research, and Innovation (PMU-B)/ ; RA65/045//Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University, grant number/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Kidney Calculi/microbiology/metabolism/therapy ; Humans ; Rats ; Male ; *Rats, Wistar ; Dysbiosis/microbiology ; Disease Models, Animal ; Feces/microbiology ; Female ; Adult ; Middle Aged ; }, abstract = {Emerging research on the microbiome highlights the significant role of gut health in the development of kidney stones, indicating that an imbalance in gut bacteria or dysbiosis can influence the formation of stones by altering oxalate metabolism and urinary metabolite profiles. In particular, the overabundance of specific bacteria such as Enterococcus and Oxalobacter spp., which are known to affect oxalate absorption, is observed in patients with urolithiasis. This study investigates the effects of gut dysbiosis on urolithiasis through fecal microbiota transplantation (FMT) from patients to rats and its impact on urinary mineral excretion and stone formation. Fecal samples from eight patients with calcium oxalate stones and ten healthy volunteers were collected to assess the gut microbiome. These samples were then transplanted to antibiotic-pretreated Wistar rats for a duration of four weeks. After transplantation, we evaluated changes in the fecal gut microbiome profile, urinary mineral excretion rates, and expression levels of intestinal zonula occluden-1 (ZO-1), SLC26A6 and renal NF-κB. In humans, patients with urolithiasis exhibited increased urinary calcium and oxalate levels, along with decreased citrate excretion and increased urinary supersaturation index. The fecal microbiota showed a notable abundance of Bacteroidota. In rodents, urolithiasis-FMT rats showed urinary disturbances similar to patients, including elevated pH, oxalate level, and supersaturation index, despite negative renal pathology. In addition, a slight elevation in the expression of renal NF-κB, a significant intestinal SLC26A6, and a reduction in ZO-1 expression were observed. The gut microbiome of urolithiasis-FMT rats showed an increased abundance of Bacteroidota, particularly Muribaculaceae, compared to their healthy FMT counterparts. In conclusion, the consistent overabundance of Bacteroidota in both urolithiasis patients and urolithiasis-FMT rats is related to altered intestinal barrier function, hyperoxaluria, and renal inflammation. These findings suggest that gut dysbiosis, characterized by an overgrowth of Bacteroidota, plays a crucial role in the pathogenesis of calcium oxalate urolithiasis, underscoring the potential of targeting the gut microbiota as a therapeutic strategy.}, }
@article {pmid39300146, year = {2024}, author = {Juhász, B and Horváth, K and Kuti, D and Shen, J and Feuchtinger, A and Zhang, C and Bata-Vidács, I and Nagy, I and Kukolya, J and Witting, M and Baranyi, M and Ferenczi, S and Walch, A and Sun, N and Kovács, KJ}, title = {Dipeptide metabolite, glutamyl-glutamate mediates microbe-host interaction to boost spermatogenesis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {21864}, pmid = {39300146}, issn = {2045-2322}, support = {SFB 824 C04//Deutsche Forschungsgemeinschaft/ ; 124424//Hungarian National Research, Development and Innovation Office/ ; -1.2.1-NKP-2017-00002//National Brain Research Program 2017/ ; RRF-2.3.1-21-2022-00011//National Laboratory of Translational Neuroscience/ ; }, mesh = {Animals ; Male ; Mice ; *Spermatogenesis ; *Dipeptides/metabolism ; *Testis/metabolism/microbiology ; Sperm Count ; Fecal Microbiota Transplantation ; Testosterone/metabolism ; Host Microbial Interactions ; Metabolomics/methods ; Gastrointestinal Microbiome ; Fertility ; }, abstract = {The decrease in sperm count and infertility is a global issue that remains unresolved. By screening environmental bacterial isolates, we have found that a novel lactic acid bacterium, Lactiplantibacillus plantarum SNI3, increased testis size, testosterone levels, sperm count, sexual activity and fertility in mice that have consumed the bacteria for four weeks. The abundance of L. plantarum in the colon microbiome was positively associated with sperm count. Fecal microbiota transplantation (FMT) from L. plantarum SNI3-dosed mice improved testicular functions in microbiome-attenuated recipient animals. To identify mediators that confer pro-reproductive effects on the host, untargeted in situ mass spectrometry metabolomics was performed on testis samples of L. plantarum SNI3-treated and control mice. Enrichment pathway analysis revealed several perturbed metabolic pathways in the testis of treated mice. Within the testis, a dipeptide, glutamyl-glutamate (GluGlu) was the most upregulated metabolite following L. plantarum SNI3 administration. To validate the pro-reproductive feature of GluGlu, systemic and local injections of the dipeptide have been performed. γ-GluGlu increased sperm count but had no effect on testosterone. These findings highlight the role of γ-GluGlu in mediating spermatogenetic effects of L. plantarum on the male mouse host and -following relevant human clinical trials- may provide future tools for treating certain forms of male infertility.}, }
@article {pmid39299827, year = {2025}, author = {Sanabani, SS}, title = {Impact of Gut Microbiota on Lymphoma: New Frontiers in Cancer Research.}, journal = {Clinical lymphoma, myeloma &amp; leukemia}, volume = {25}, number = {2}, pages = {e82-e89}, doi = {10.1016/j.clml.2024.08.008}, pmid = {39299827}, issn = {2152-2669}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Lymphoma/therapy/etiology/microbiology/diagnosis ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiome (GMB), which is made up of various microorganisms, plays a crucial role in maintaining the health of the host. Disruptions in this delicate ecosystem, known as microbial dysbiosis, have been linked to various diseases, including hematologic malignancies such as lymphoma. This review article explores the complex relationship between the GMB and the development of lymphoma and highlights its implications for diagnostic and therapeutic approaches. It discusses how GMB influences lymphoma development directly through the presence of certain microorganisms and indirectly through changes in the immune system. The clinical relevance of GMB is highlighted and its potential utility for diagnosis, predicting treatment outcomes and developing personalized therapeutic strategies for lymphoma patients is demonstrated. The review also looks at microbiome-targeted interventions such as fecal microbiome transplantation and dietary modification, which have shown promise for treating microbial dysbiosis and improving patient outcomes. In addition, it highlights the analytical challenges and the need for further research to fully elucidate the mechanistic functions of the GMB in the context of lymphoma. This review emphasizes the critical role of GMB in lymphomagenesis and its potential for the development of diagnostic and therapeutic strategies.}, }
@article {pmid39299249, year = {2025}, author = {Aubert, O and Irvine, WFE and Aminoff, D and de Blaauw, I and Cascio, S and Cretolle, C and Iacobelli, BD and Mantzios, K and Midrio, P and Miserez, M and Sarnacki, S and Schmiedeke, E and Schwarzer, N and Sloots, C and Stenström, P and Lacher, M and Gosemann, JH}, title = {European Reference Network eUROGEN Guidelines on the Management of Anorectal Malformations, Part II: Treatment.}, journal = {European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie}, volume = {35}, number = {2}, pages = {112-119}, doi = {10.1055/s-0044-1791257}, pmid = {39299249}, issn = {1439-359X}, mesh = {Humans ; *Anorectal Malformations/therapy/surgery/diagnosis ; Europe ; Fecal Incontinence/therapy/etiology ; Anal Canal/abnormalities ; Urinary Incontinence/therapy/etiology ; }, abstract = {INTRODUCTION: Anorectal malformations (ARMs) are rare birth defects affecting the anorectum and oftentimes the genitourinary region. The management of ARM patients is complex and requires highly specialized surgical and medical care. The European Reference Network eUROGEN for rare and complex urogenital conditions aimed to develop comprehensive guidelines for the management of ARM applicable on a European level.<br><br>METHODS: &#x2003;The Dutch Quality Standard for ARM served as the basis for the development of guidelines. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from seven European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering the current evidence, expert opinion, and the European context.<br><br>RESULTS: &#x2003;Surgical and medical treatment of ARM, postoperative instructions, toilet training, and management of fecal and urinary incontinence were addressed. Seven new studies were identified. The panel adapted 23 recommendations, adopted 3, and developed 8 de novo. The overall level of newly found evidence was considered low.<br><br>CONCLUSION: &#x2003;Treatment of ARM patients requires a multidisciplinary team and expertise about anatomical and surgical aspects of the disease, as well as long-term follow-up. This guideline offers recommendations for surgical and medical treatment of ARM and associated complications, according to the best available evidence and applicable on a European level.}, }
@article {pmid39298907, year = {2024}, author = {Kaul, R and Paul, P and Harfouche, M and Ayyan, M and Laws, S and Chaari, A}, title = {The effect of microbiome-modulating therapeutics on glucose homeostasis in metabolic syndrome: A systematic review, meta-analysis, and meta-regression of clinical trials.}, journal = {Diabetes &amp; metabolic syndrome}, volume = {18}, number = {8}, pages = {103118}, doi = {10.1016/j.dsx.2024.103118}, pmid = {39298907}, issn = {1878-0334}, mesh = {Humans ; *Metabolic Syndrome/therapy/microbiology ; *Homeostasis ; *Blood Glucose/analysis/metabolism ; Probiotics/therapeutic use ; Gastrointestinal Microbiome ; Clinical Trials as Topic ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; Prognosis ; }, abstract = {BACKGROUND: Metabolic syndrome (MetS) is a chronic disorder featuring overweight/obesity, high blood pressure, and dysfunction of lipid and carbohydrate metabolism. Microbiome-modulating probiotics, prebiotics, synbiotics and fecal microbiota transplant (FMT) are promising adjunct therapies for improving parameters of glucose homeostasis and insulinemia.<br><br>METHODS: We conducted a comprehensive systematic review, meta-analyses, and meta-regressions to investigate the effect of the abovementioned microbiome therapies on various biomarkers after screening clinical trials published through April 2023. We pooled data using random effects meta-analyses, reporting them as mean differences (MDs) with 95&#xa0;% confidence intervals (CIs), and conducting univariate linear model meta-regressions.<br><br>RESULTS: Data from 21 trial comparisons across 19 studies (n&#xa0;=&#xa0;911) revealed that, compared to placebo/control, microbiome-modulating therapies were associated with statistically significant changes in fasting plasma glucose (MD: 4.03&#xa0;mg/dL [95%CI: 6.93; -1.13]; p effect&#xa0;=&#xa0;0.006, I[2]&#xa0;=&#xa0;89.8&#xa0;%), and fasting insulin (MD: 2.56 &#x3bc;U/mL [95%CI: 4.28; -0.84]; p effect&#xa0;=&#xa0;0.004, I[2]&#xa0;=&#xa0;87.9&#xa0;%), but not insulin resistance or sensitivity indices and HbA1c. Age, baseline BMI, baseline biomarker value, pro/synbiotic dosage, trial duration, nutraceutical type, and WHO region were factors affecting the efficacy of these interventions at producing changes in biomarkers, signaling the potential role of personalized precision medicine adjunct therapy for deranged glucose homeostasis in patients with MetS. Nevertheless, presence of heterogeneity calls for further investigation before their clinical application.<br><br>CONCLUSIONS: Probiotics, prebiotics, synbiotics and FMT supplementation improved fasting glucose and insulin in patients with MetS. Further large-scale and high-quality trials are required before potential clinical applications.}, }
@article {pmid39298815, year = {2024}, author = {Wang, XZ and Huang, JL and Zhang, J and Li, QH and Zhang, PP and Wu, C and Jia, YY and Su, H and Sun, X}, title = {Fecal microbiota transplantation as a new way for OVA-induced atopic dermatitis of juvenile mice.}, journal = {International immunopharmacology}, volume = {142}, number = {Pt B}, pages = {113183}, doi = {10.1016/j.intimp.2024.113183}, pmid = {39298815}, issn = {1878-1705}, mesh = {Animals ; *Dermatitis, Atopic/therapy/immunology/microbiology ; *Fecal Microbiota Transplantation ; *Ovalbumin/immunology ; *Gastrointestinal Microbiome/immunology ; Mice ; *Disease Models, Animal ; Mice, Inbred BALB C ; Immunoglobulin E/blood/immunology ; T-Lymphocytes, Regulatory/immunology ; Female ; Skin/pathology/immunology/microbiology ; Programmed Cell Death 1 Receptor/metabolism ; B7-H1 Antigen/metabolism/genetics ; Humans ; Allergens/immunology ; Immune Tolerance ; Cytokines/metabolism ; }, abstract = {Children all over the world suffer from atopic dermatitis (AD), a prevalent condition that impairs their health. Corticosteroids, which have long-term negative effects, are frequently used to treat AD. There has been a growing body of research on the gut microbiota's function in AD. Nevertheless, the function and underlying mechanisms of fecal microbiota transplantation (FMT) in AD children remain to be established. Therefore, in order to assess the preventive effects of FMT treatment on AD and investigate the mechanisms, we constructed an ovalbumin (OVA)-induced juvenile mouse AD model in this investigation. This study explored the role and mechanism of FMT treatment in AD through 16S RNA sequencing, pathological histological staining, molecular biology, and Flow cytometry. Results demonstrated that the FMT treatment improved the gut microbiota's diversity and composition, bringing it back to a level similar to that of a close donor. Following FMT treatment, OVA-specific antibodies were inhibited, immunoglobulin (Ig) E production was decreased, the quantity of mast cells and eosinophils was decreased, and specific inflammatory markers in the skin and serum were decreased. Further mechanistic studies revealed that FMT treatment induced CD103[+] DCs and programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression in skin-draining lymph nodes and promoted Treg production to induce immune tolerance and suppress skin inflammation. Meanwhile, changes in the gut microbiota were substantially correlated with Th2 cytokines, OVA-specific antibodies, and PD-L1/PD-1. In conclusion, FMT regulates the Th1/Th2 immunological balance and the gut microbiota. It may also inhibit AD-induced allergy responses through the PD-L1/PD-1 pathway, and providing a unique idea and possibly a fresh approach to the treatment of AD.}, }
@article {pmid39295732, year = {2024}, author = {Wang, S and Yuan, Z and Gao, X and Wu, J and Ren, Y and Yu, X and Li, J and Wei, W}, title = {Global research trends on the links between gut microbiota and radiotherapy: a bibliometric analysis (2004-2023).}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1414196}, pmid = {39295732}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; *Bibliometrics ; Humans ; *Radiotherapy ; China ; }, abstract = {BACKGROUND: There is a crosstalk between gut microbiota and radiotherapy. The aim of this study is to use bibliometric analysis to explore the research status and development trends of research on gut microbiota and radiotherapy.<br><br>METHODS: A literature search regarding publications on gut microbiota and radiotherapy from 2004 to 2023 was retrieved. CiteSpace and VOSviewer were used to conduct the bibliometric analysis. The growth rate of publications, leading countries and institutions, preferred journals, top authors and co-cited authors, top co-cited references, keywords and citation were analyzed in this study.<br><br>RESULTS: A total of 2821 papers were extracted. The number of papers has increased rapidly over the past decade, especially after 2017. The USA and China had the most publications and made great contributions to this field. The Chinese Academy of Sciences stood out as the institution with the highest number of publications, followed by the Chinese Academy of Medical Sciences &amp; Peking Union Medical College. The most influential authors were Fan Saijun and Li Yuan. PLoS One had the most publications and the most total citations. Highly cited papers and high-frequency keywords illustrated the current status and trends. Furthermore, analysis of keyword with burst revealed that immunotherapy, acid, intestinal barrier, therapy, immunotherapy, fecal microbiota transplantation, etc, are at the forefront of research in this area.<br><br>CONCLUSION: This study provides an overview of research on gut microbiota and radiotherapy, highlighting influential contributors, impactful publications, and emerging trends. Our finding suggests avenues for further exploration to improve clinical outcomes.}, }
@article {pmid39293564, year = {2024}, author = {Zhang, M and Yin, YS and May, KS and Wang, S and Purcell, H and Zhang, XS and Blaser, MJ and den Hartigh, LJ}, title = {The role of intestinal microbiota in physiologic and body compositional changes that accompany CLA-mediated weight loss in obese mice.}, journal = {Molecular metabolism}, volume = {89}, number = {}, pages = {102029}, pmid = {39293564}, issn = {2212-8778}, support = {T32 HL007028/HL/NHLBI NIH HHS/United States ; T32 DK007247/DK/NIDDK NIH HHS/United States ; U01 AI122285/AI/NIAID NIH HHS/United States ; P30 ES005022/ES/NIEHS NIH HHS/United States ; P30 DK035816/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Mice ; Male ; *Gastrointestinal Microbiome ; *Obesity/metabolism/microbiology ; *Weight Loss ; *Mice, Inbred C57BL ; *Linoleic Acids, Conjugated/metabolism/pharmacology ; Energy Metabolism ; Mice, Obese ; Body Composition ; Fatty Acids, Volatile/metabolism ; Diet, High-Fat/adverse effects ; Butyrates/metabolism ; Cecum/metabolism/microbiology ; Anti-Bacterial Agents/pharmacology ; }, abstract = {OBJECTIVE: Obesity continues to be a major problem, despite known treatment strategies such as lifestyle modifications, pharmaceuticals, and surgical options, necessitating the development of novel weight loss approaches. The naturally occurring fatty acid, 10,12 conjugated linoleic acid (10,12 CLA), promotes weight loss by increasing fat oxidation and browning of white adipose tissue, leading to increased energy expenditure in obese mice. Coincident with weight loss, 10,12 CLA also alters the murine gut microbiota by enriching for microbes that produce short chain fatty acids (SCFAs), with concurrent elevations in fecal butyrate and plasma acetate.<br><br>METHODS: To determine if the observed microbiota changes are required for 10,12 CLA-mediated weight loss, adult male mice with diet-induced obesity were given broad-spectrum antibiotics (ABX) to perturb the microbiota prior to and during 10,12 CLA-mediated weight loss. Conversely, to determine whether gut microbes were sufficient to induce weight loss, conventionally-raised and germ-free mice were transplanted with cecal contents from mice that had undergone weight loss by 10,12 CLA supplementation.<br><br>RESULTS: While body weight was minimally modulated by ABX-mediated perturbation of gut bacterial populations, adult male mice given ABX were more resistant to the increased energy expenditure and fat loss that are induced by 10,12 CLA supplementation. Transplanting cecal contents from donor mice losing weight due to oral 10,12 CLA consumption into conventional or germ-free mice led to improved glucose metabolism with increased butyrate production.<br><br>CONCLUSIONS: These data suggest a critical role for the microbiota in diet-modulated changes in energy balance and glucose metabolism, and distinguish the metabolic effects of orally delivered 10,12 CLA from cecal transplantation of the resulting microbiota.}, }
@article {pmid39293366, year = {2024}, author = {Chen, S and Xue, X and Zhang, H and Huang, X and Lin, X and He, J and Chen, L and Luo, S and Gao, J}, title = {Jianwei Shoutai Pills alleviates miscarriage by modulating gut microbial production of BAs and NLRP3-inflammasome at the maternal-fetal interface of rats.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156000}, doi = {10.1016/j.phymed.2024.156000}, pmid = {39293366}, issn = {1618-095X}, mesh = {Animals ; Female ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology ; Pregnancy ; *Abortion, Spontaneous ; *Rats, Sprague-Dawley ; *Inflammasomes/metabolism ; Rats ; Bile Acids and Salts/metabolism ; Disease Models, Animal ; Uterus/drug effects ; }, abstract = {BACKGROUND: Miscarriage has the characteristics of recurrent attacks and complex etiology, so it is gradually attracted the wide attention of scholars in the fields of reproduction. Potential association between gut microbiome (GM) and pregnancy disorders has been investigated. Jianwei Shoutai pills (JWP), as a representative formula, have been proven to have protective effect in both clinical and experimental research in miscarriage. However, the specific mechanism of JWP in miscarriage through GM remains unclear.<br><br>PURPOSE: To investigate the underlying mechanism of JWP against miscarriage through the gut-uterus axis.<br><br>METHODS: The effects of JWP on an RU486-induced rat model of miscarriage were evaluated by embryo resorption rate, vaginal bleeding rate, and appearance of the uterus and embryo. We used 16S rRNA sequencing to measure the extent of the effect of JWP on GM of rats with miscarriage. Bile acid (BA) content of the feces of rats treated with JWP was evaluated by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS). The activation of bile acid-associated receptor, Farnesoid X receptor (FXR), was evaluated by immunofluorescence. The expression level of NLRP3 inflammasome-associated protein was detected by Western blot or Elisa. Fecal microbiota transplantation (FMT) was used to confirm that GM was essential for the therapeutic effect of JWP in miscarriage.<br><br>RESULTS: JWP significantly ameliorated miscarriage symptoms and embryo resorption rate caused by RU486-induced miscarriage as well as restored the abnormal activation of NLRP3-inflammasome at the maternal-fetal interface. Furthermore, JWP can significantly regulated GM dysbiosis and closely associated with BA metabolism by KEGG pathway prediction analysis. Several BA content were significantly restored by HPLC-MS. The expression of NLRP3 inflammasome-associated protein at maternal-fetal interface was reversed by JWP. Combined with FMT, JWP could regulate activation of NLRP3 at the maternal-fetal interface by BAs produced by GM.<br><br>CONCLUSION: JWP restored abnormal activation of the NLRP3-inflammasome in an RU486-induced miscarriage rat model, and corrected the BA disorder by regulating imbalance of the GM.}, }
@article {pmid39292598, year = {2024}, author = {Goldsmith, J and Tomkovich, S and Auniņš, JG and McGovern, BH and Mahoney, JC and Hasson, BR and McChalicher, CWJ and Ege, DS}, title = {End-to-end donor screening and manufacturing controls: complementary quality-based strategies to minimize patient risk for donor-derived microbiome therapeutics.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2402550}, pmid = {39292598}, issn = {1949-0984}, mesh = {Humans ; *Donor Selection/organization &amp; administration ; *Fecal Microbiota Transplantation/adverse effects ; *Feces/microbiology ; *Gastrointestinal Microbiome ; }, abstract = {Advances in microbiome therapeutics have been motivated by a deeper understanding of the role that the gastrointestinal microbiome plays in human health and disease. The FDA approval of two stool-derived live biotherapeutic products (LBPs), REBYOTA® 150 mL enema (fecal microbiota, live-jslm; formerly RBX2660) and VOWST® oral capsules (fecal microbiota spores, live-brpk; formerly SER-109), for the prevention of recurrent CDI in adults following antibiotic treatment for recurrent CDI provides promise and insights for the development of LBPs for other diseases associated with microbiome dysfunction. Donor-derived products carry risk of disease transmission that must be mitigated through a robust donor screening program and downstream manufacturing controls. Most published recommendations for donor screening practices are prescriptive and do not include a systematic, risk-based approach for donor stool-derived products. A general framework for an end-to-end donor screening program is needed using risk management strategies for donor-derived microbiome therapeutic using a matrixed approach, combining the elements of donor screening with manufacturing controls that are designed to minimize risk to patients. A donor screening paradigm that incorporates medical history, physical examination, laboratory testing, and donor sample inspection are only the first steps in reducing risk of transmission of infectious agents. Manufacturing controls are the cornerstone of risk mitigation when screening unwittingly fails. Failure Mode and Effects Analysis (FMEA) can be used as a tool to assess for residual risk that requires further donor or manufacturing controls. Together, a well-reasoned donor program and manufacturing controls are complementary strategies that must be revisited and reexamined frequently with constant vigilance to mitigate risk to patients. In the spirit of full disclosure and informed consent, physicians should discuss any limitations in the donor screening and manufacturing processes with their patients prior to treatment with microbiome-based therapeutics.}, }
@article {pmid39290901, year = {2024}, author = {Polak, K and Muszyński, T and Frątczak, A and Meznerics, F and Bánvölgyi, A and Kiss, N and Miziołek, B and Bergler-Czop, B}, title = {Study of gut microbiome alterations in plaque psoriasis patients compared to healthy individuals.}, journal = {Postepy dermatologii i alergologii}, volume = {41}, number = {4}, pages = {378-387}, pmid = {39290901}, issn = {1642-395X}, abstract = {INTRODUCTION: Many studies have shown significant alterations in the gut microbiome of patients with psoriasis compared to healthy controls.<br><br>AIM: The primary objective of the current research was to explore the impact of gut microbiome composition on the progression and severity of plaque psoriasis.<br><br>MATERIAL AND METHODS: A total of 20 patients with moderate-to-severe psoriasis and 20 healthy individuals were recruited and provided a stool sample to assess the gut microbiome. After the samples were prepared according to the NGS library preparation workflow, they were sequenced using the Illumina platform and the report was generated that underwent statistical analysis.<br><br>RESULTS: The microbiome profiles of psoriasis patients exhibited significant differences compared to healthy controls as evidenced by the statistical analysis of various bacterial genera, with the median abundance significantly lower in psoriasis patients compared to healthy controls (p = 0.033). The analysis of the Firmicutes-to-Bacteroidetes ratio, a commonly evaluated marker of dysbiosis, did not reach statistical significance (p = 0.239). However, there was a noticeable trend towards a higher median ratio in psoriasis patients compared to healthy controls. The ratio did not show significant associations with PASI or BSA but trends towards significance with DLQI (B = -12.11, p = 0.095).<br><br>CONCLUSIONS: Overall, the above findings underscore the importance of the gut microbiome in psoriasis and suggest that modulation of specific bacterial genera, especially that with significant differences, could be a potential strategy for therapeutic intervention. Targeting these depleted genera through microbiome-based interventions, such as probiotic supplementation or faecal microbiota transplantation, could potentially help to restore gut homeostasis and alleviate the inflammatory burden in psoriasis.}, }
@article {pmid39289768, year = {2024}, author = {Lo, SW and Hung, TH and Lin, YT and Lee, CS and Chen, CY and Fang, CJ and Lai, PC}, title = {Clinical efficacy and safety of faecal microbiota transplantation in the treatment of irritable bowel syndrome: a systematic review, meta-analysis and trial sequential analysis.}, journal = {European journal of medical research}, volume = {29}, number = {1}, pages = {464}, pmid = {39289768}, issn = {2047-783X}, support = {NCKUH-11304017//National Cheng Kung University Hospital/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Irritable Bowel Syndrome/therapy ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: The aim of this study is to evaluate the efficacy and safety of faecal microbiota transplantation (FMT) for the treatment of irritable bowel syndrome (IBS).<br><br>METHODS: We searched four databases for randomised controlled trials (RCTs) that compared FMT with a control intervention in patients with IBS. The revised Cochrane risk-of-bias (RoB) tool was chosen for appraisal. Meta-analysis with trial sequential analysis (TSA) was conducted. Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence (CoE).<br><br>RESULTS: We included 12 RCTs with a total of 615 participants. Meta-analyses showed no significant difference between the FMT and control groups in terms of clinical responses (relative risk [RR]&#x2009;=&#x2009;1.44, 95% confidence interval [CI] 0.88-2.33) and changes in IBS Severity Scoring System (IBS-SSS) scores (standardised mean difference [SMD]&#x2009;=&#x2009;&#x2009;-&#x2009;0.31, 95% CI &#x2009;-&#x2009;0.72 to 0.09) and IBS Quality of Life (IBS-QOL) scores (SMD&#x2009;=&#x2009;0.30, 95% CI &#x2009;-&#x2009;0.09 to 0.69). Subgroup analysis revealed that in studies with low RoB and using endoscopy, nasojejunal tube and rectal enema delivery, FMT led to a significant improvement in clinical responses and changes in IBS-SSS and IBS-QOL scores. TSA suggested that the current evidence is inconclusive and that the CoE is very low.<br><br>CONCLUSION: This study suggests that patients with IBS may benefit from FMT especially when it is administered via endoscopy, nasojejunal tube or rectal enema. However, the certainty of evidence is very low. Further research is needed to confirm the efficacy and safety of FMT for IBS treatment.<br><br>TRIAL REGISTRATION: PROSPERO registration number CRD42020211002.}, }
@article {pmid39288846, year = {2024}, author = {Chen, Q and Cheng, W and Zhang, J and Chi, C and Lin, M and He, C and Liao, Z and Gong, F}, title = {Fibroblast growth factor 21 improves insulin sensitivity by modulating the bile acid-gut microbiota axis in type Ⅱ diabetic mice.}, journal = {Free radical biology &amp; medicine}, volume = {224}, number = {}, pages = {600-617}, doi = {10.1016/j.freeradbiomed.2024.09.017}, pmid = {39288846}, issn = {1873-4596}, mesh = {Animals ; *Fibroblast Growth Factors/metabolism/genetics ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Diabetes Mellitus, Type 2/metabolism/microbiology ; *Insulin Resistance ; *Diabetes Mellitus, Experimental/metabolism/microbiology ; *Bile Acids and Salts/metabolism ; Male ; *Glucagon-Like Peptide 1/metabolism/blood ; Mice, Knockout ; Fatty Acids, Volatile/metabolism ; Lipopolysaccharides ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Streptozocin ; Feces/microbiology ; }, abstract = {BACKGROUND: Fibroblast growth factor 21 (FGF21) is an important regulator of glycolipid metabolism. However, whether the gut microbiota is related to the anti-diabetic and obesity effects of FGF21 remains unclear.<br><br>METHODS: Our research used KO/KO db/db male mice and streptozotocin (STZ)-induced to simulate the construction of two type II diabetic mellitus (T2DM) models, and detected impaired glucose tolerance in the model by using the ipGTT and ITT assays, and collected feces from the model mice for sequencing of the intestinal flora and the content of short-chain fatty acids. H&#xff06;E staining was used to detect changes in intestinal tissue, the serum levels of LPS and GLP-1 were detected by ELISA.<br><br>RESULTS: In this study, we found that FGF21 significantly improved insulin sensitivity, attenuated intestinal lesions, and decreased serum lipopolysaccharide (LPS) concentrations in T2DM mice. Moreover, FGF21 reshaped the gut microbiota and altered their metabolic pathways in T2DM mice, promoting the production of short-chain fatty acids (SCFAs) and the secretion of glucagon-like peptide 1 (GLP-1). Fecal transplantation experiments further confirmed that feces from FGF21-treated diabetic mice demonstrated similar effects as FGF21 in terms of anti-diabetic activity and regulation of gut microbiota dysbiosis. Additionally, the antibiotic depletion of gut microbiota abolished the beneficial effects of FGF21, including increased GLP-1 secretion and fecal SCFA concentration. Additionally, the FGF21 effects of ameliorating intestinal damage and suppressing plasma LPS secretion were suppressed. All these findings suggest that FGF21 prevents intestinal lesions by modifying the gut microbiota composition. Furthermore, FGF21 affected bile acid synthesis by inhibiting CYP7A1, the key enzyme of bile acid synthesis.<br><br>CONCLUSSION: Therefore, FGF21 enriched beneficial bacteria by preventing bile acid synthesis and stimulating the secretion of the intestinal hormone GLP-1 via the increased production of gut microbiota metabolites, thereby exerting its anti-diabetic effects.}, }
@article {pmid39287858, year = {2024}, author = {Engin, ED}, title = {Microbiota and Lipotoxicity.}, journal = {Advances in experimental medicine and biology}, volume = {1460}, number = {}, pages = {357-372}, pmid = {39287858}, issn = {0065-2598}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis ; *Metabolic Syndrome/microbiology/metabolism ; *Obesity/microbiology/metabolism ; Animals ; Lipid Metabolism ; Inflammation/metabolism/microbiology ; Adipose Tissue/metabolism/immunology ; }, abstract = {Gut microbiota is an indispensable commensal partner of human superorganism. The wealth of genetic repertoire provided by these microorganisms extends host's substrate processing capability. Energy and nutrient harvesting machinery primarily depends on the proper function of these organisms. However, the dynamic composition of microbiota changes with age, lifestyle, stress factors, infections, medications, and host pathophysiological conditions. Host immune system is primarily responsible for shaping up the microbial community and sustaining the symbiotic state. This involves controlling the delicate balance between agility toward pathobionts and tolerance toward symbionts. When things go wrong with this crosstalk, dysbiosis may arise.Metabolic syndrome is a multisystemic, low-grade chronic inflammatory disease that involves dyslipidemia, glucose intolerance, insulin resistance, and central obesity. Excess caloric intake with high-sugar and high-fat diet promote high energy harvesting and lipogenesis. The secretion of adipokines accompanies lipid spillover from fat cells, which contribute to insulin resistance and the expansion of adipose tissue in ectopic sites. Proinflammatory cytokines from adipose tissue macrophages increase the extent of adipose dysfunction.The inflammatory nature of obesity and metabolic syndrome recall the connection between dysbiosis and immune dysfunction. A remarkable association exits between obesity, inflammatory bowel disease, gluten-sensitive enteropathy, and dysbiosis. These conditions compromise the gut mucosa barrier and allow lipopolysaccharide to enter circulation. Unresolved chronic inflammation caused by one condition may overlap or trigger the other(s). Experimental studies and therapeutic trials of fecal microbiota transplantation promise limited improvement in some of these conditions.Typically, metabolic syndrome is considered as a consequence of overnutrition and the vicious cycle of lipogenesis, lipid accumulation, and chronic low-level inflammation. Because of the complex nature of this disorder, it remains inconclusive whether dysbiosis is a cause or consequence of obesity and metabolic syndrome.}, }
@article {pmid39287045, year = {2024}, author = {Li, N and Han, X and Ruan, M and Huang, F and Yang, L and Xu, T and Wang, H and Wu, H and Shi, S and Wang, Y and Wu, X and Wang, S}, title = {Prebiotic inulin controls Th17 cells mediated central nervous system autoimmunity through modulating the gut microbiota and short chain fatty acids.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2402547}, pmid = {39287045}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Inulin/administration &amp; dosage/pharmacology ; *Encephalomyelitis, Autoimmune, Experimental/immunology/drug therapy/microbiology ; *Th17 Cells/immunology ; Mice ; *Prebiotics/administration &amp; dosage ; *Mice, Inbred C57BL ; Female ; *Fatty Acids, Volatile/metabolism ; *Autoimmunity/drug effects ; *Multiple Sclerosis/immunology/drug therapy/microbiology ; Central Nervous System/immunology ; Bacteria/classification/isolation &amp; purification ; }, abstract = {Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination occurring in the central nervous system (CNS). Inulin is a common prebiotic that can improve metabolic disorders by modulating the gut microbiota. However, its capacity to affect CNS autoimmunity is poorly recognized. Experimental autoimmune encephalomyelitis (EAE) is a classical mouse model of MS. Herein, we found that oral administration of inulin ameliorated the severity EAE in mice, accompanied by reductions in inflammatory cell infiltration and demyelination in the CNS. These reductions were associated with decreased proportion and numbers of Th17 cells in brain and spleen. Consistent with the findings, the serum concentrations of IL-17, IL-6, and TNF-α were reduced in inulin treated EAE mice. Moreover, the proliferation of auto-reactive lymphocytes, against MOG35-55 antigen, was attenuated ex vivo. Mechanistically, inulin treatment altered the composition of gut microbiota. It increased Lactobacillus and Dubosiella whereas decreased g_Prevotellaceae_NK3B31_group at the genus level, alongside with elevated concentration of butyric acid in fecal content and serum. In vitro, butyrate, but not inulin, could inhibit the activation of MOG35-55 stimulated lymphocytes. Furthermore, fecal microbiota transplantation assay confirmed that fecal contents of inulin-treated normal mice had an ameliorative effect on EAE mice. In contrast, antibiotic cocktail (ABX) treatment diminished the therapeutic effect of inulin in EAE mice as well as the reduction of Th17 cells, while supplementation with Lactobacillus reuteri restored the amelioration effect. These results confirmed that the attenuation of inulin on Th17 cells and inflammatory demyelination in EAE mice was dependent on its modulation on gut microbiota and metabolites. Our findings provide a potential therapeutic regimen for prebiotic inulin supplementation in patients with multiple sclerosis.}, }
@article {pmid39285046, year = {2025}, author = {Wang, Z and Gong, M and Fang, Y and Yuan, H and Zhang, C}, title = {Reconstruction characteristics of gut microbiota from patients with type 1 diabetes affect the phenotypic reproducibility of glucose metabolism in mice.}, journal = {Science China. Life sciences}, volume = {68}, number = {1}, pages = {176-188}, pmid = {39285046}, issn = {1869-1889}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; *Diabetes Mellitus, Type 1/microbiology/metabolism ; Mice ; *Phenotype ; *Glucose/metabolism ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Reproducibility of Results ; Male ; Disease Models, Animal ; Female ; Germ-Free Life ; }, abstract = {The human microbiota-associated (HMA) mice model, especially the germ-free (GF)-humanized mice, has been widely used to probe the causal relationships between gut microbiota and human diseases such as type 1 diabetes (T1D). However, most studies have not clarified the extent to which the reconstruction of the human donor microbiota in recipient mice correlates with corresponding phenotypic reproducibility. In this study, we transplanted fecal microbiota from five patients with T1D and four healthy people into GF mice, and microbiota from each donor were transplanted into 10 mice. Mice with similar microbiota structure to the donor exhibited better phenotypic reproducibility. The characteristics of the microbial community assembly of donors also influenced the phenotypic reproducibility in mice, and individuals with a higher proportion of stochastic processes showed more severe disorders. Microbes enriched in patients with T1D had a stronger colonization potential in mice with impaired glucose metabolism, and microbiota functional features related to T1D were better reproduced in these mice. This indicates that assembly traits and colonization efficacy of microbiota influence phenotypic reproducibility in GF-humanized mice. Our findings provide important insights for using HMA mice models to explore links between gut microbiota and human diseases.}, }
@article {pmid39283061, year = {2024}, author = {McBurney, MI and Cho, CE}, title = {Understanding the role of the human gut microbiome in overweight and obesity.}, journal = {Annals of the New York Academy of Sciences}, volume = {1540}, number = {1}, pages = {61-88}, doi = {10.1111/nyas.15215}, pmid = {39283061}, issn = {1749-6632}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Obesity/microbiology/metabolism ; *Overweight/microbiology ; Probiotics ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Diet ; }, abstract = {The gut microbiome may be related to the prevalence of overweight and obesity, but high interindividual variability of the human microbiome complicates our understanding. Obesity often occurs concomitantly with micronutrient deficiencies that impair energy metabolism. Microbiota composition is affected by diet. Host-microbiota interactions are bidirectional. We propose three pathways whereby these interactions may modulate the gut microbiome and obesity: (1) ingested compounds or derivatives affecting small intestinal transit, endogenous secretions, digestion, absorption, microbiome balance, and gut barrier function directly affect host metabolism; (2) substrate availability affecting colonic microbial composition and contact with the gut barrier; and (3) microbial end products affecting host metabolism. The quantity/concentration, duration, and/or frequency (circadian rhythm) of changes in these pathways can alter the gut microbiome, disrupt the gut barrier, alter host immunity, and increase the risk of and progression to overweight and obesity. Host-specific characteristics (e.g., genetic variations) may further affect individual sensitivity and/or resilience to diet- and microbiome-associated perturbations in the colonic environment. In this narrative review, the effects of selected interventions, including fecal microbiota transplantation, dietary calorie restriction, dietary fibers and prebiotics, probiotics and synbiotics, vitamins, minerals, and fatty acids, on the gut microbiome, body weight, and/or adiposity are summarized to help identify mechanisms of action and research opportunities.}, }
@article {pmid39282548, year = {2024}, author = {Salvati, F and Catania, F and Murri, R and Fantoni, M and Torti, C}, title = {Clostridioides difficile infection: an update.}, journal = {Le infezioni in medicina}, volume = {32}, number = {3}, pages = {280-291}, pmid = {39282548}, issn = {2532-8689}, abstract = {Clostridioides difficile (C. difficile) is a Gram-positive, spore-forming anaerobic bacterium emerged as a leading cause of diarrhea globally. CDI's (Clostridioides difficile infection) impact on healthcare systems is concerning due to high treatment cost and increased hospitalisation time. The incidence of CDI has been influenced by hypervirulent strains such as the 027 ribotype, responsible for significant outbreaks in North America and Europe. CDI's epidemiology has evolved, showing increased community-acquired cases alongside traditional hospital-acquired infections. Mortality rates remain high, with recurrent infections further elevating the risk. Transmission of C. difficile primarily occurs via spores, which survive in healthcare settings and play a pivotal role in transmission. Not only health workers, but also the food chain could have a significant impact on the transmission of infection, although no confirmed foodborne cases have been documented. Pathogenicity of C. difficile involves spore germination and toxin production. Toxins A and B can cause cellular damage and inflammatory responses in the host, leading to colitis. Clinical picture can range from mild diarrhea to fulminant colitis with toxic megacolon, and bowel perforation. Risk factors for CDI include antibiotic exposure, advanced age, hospitalization, and use of proton pump inhibitors. Patients who experience abdominal surgery or patients with inflammatory bowel disease (IBD) are particularly susceptible due to their compromised gut microbiota. Management of CDI has evolved, with fidaxomicin emerging as a superior treatment option over vancomycin for initial and recurrent infections due to its reduction of recurrence rate. Faecal microbiota transplantation (FMT) is effective for recurrent CDI, restoring gut eubiosis. Bezlotoxumab, a monoclonal antibody against C. difficile toxin B, has shown promise in reducing recurrence rates. Severe cases of CDI may require surgical intervention, particularly in instances of toxic megacolon or bowel perforation. In conclusion, CDI remains a significant clinical entity. Further research are needed to improve patients' outcome and reduce the burden on healthcare systems.}, }
@article {pmid39282183, year = {2024}, author = {Mishra, V and Mishra, Y}, title = {Role of Gut Microbiome in Cancer Treatment.}, journal = {Indian journal of microbiology}, volume = {64}, number = {3}, pages = {1310-1325}, pmid = {39282183}, issn = {0046-8991}, abstract = {The gut microbiota influences the effectiveness and side effects of cancer treatments, particularly immunotherapy and associated immune-related complications. This important involvement of the microbiome is supported by the patients receiving antibiotics responding poorly to immunotherapy. Relatively few research has examined the underlying processes, and until recently, data regarding the detection of the microbial organisms that trigger these effects were inconsistent. Since then, a deeper comprehension of the processes of action and taxonomic classification of the relevant species has been attained. It's been demonstrated that certain bacterial species can enhance the body's reaction to immune checkpoint inhibitors through the release of distinct metabolites or products. Nonetheless, in certain patients who are not responding, Gram-negative bacteria may have a dominating suppressive impact. Patients' propensity to react to immunotherapy can be somewhat accurately predicted by machine learning techniques based on their microbiome makeup. Consequently, there has been an increase in interest in modifying the microbiome makeup to enhance patient reaction to medication. Clinical proof-of-concept studies demonstrate that dietary modifications or fecal microbiota transplantation (FMT) might be used therapeutically to increase the efficacy of immunotherapy in cancer patients. Current developments and new approaches for microbiota-based cancer treatments have been emphasized. In conclusion, preclinical research on animals and human clinical trials has made tremendous progress in our understanding of the function of the gut microbiome in health and illness. These investigations have shed light on the effects of food, FMT, probiotics, prebiotics, and microbiome-disease connections. However, there are still a lot of issues and restrictions that must be resolved before this research can be used in real-world clinical settings.}, }
@article {pmid39282181, year = {2024}, author = {Kamath, HS and Shukla, R and Shah, U and Patel, S and Das, S and Chordia, A and Satish, P and Ghosh, D}, title = {Role of Gut Microbiota in Predisposition to Colon Cancer: A Narrative Review.}, journal = {Indian journal of microbiology}, volume = {64}, number = {3}, pages = {1-13}, pmid = {39282181}, issn = {0046-8991}, abstract = {Globally, colorectal cancer (CRC) is a leading cause of cancer-related mortality. Dietary habits, inflammation, hereditary characteristics, and gut microbiota are some of its causes. The gut microbiota, a diverse population of bacteria living in the digestive system, has an impact on a variety of parameters, including inflammation, DNA damage, and immune response. The gut microbiome has a significant role in colon cancer susceptibility. Many studies have highlighted dysbiosis, an imbalance in the gut microbiota's makeup, as a major factor in colon cancer susceptibility. Dysbiosis has the potential to produce toxic metabolites and pro-inflammatory substances, which can hasten the growth of tumours. The ability of the gut microbiota to affect the host's immune system can also influence whether cancer develops or not. By better comprehending these complex interactions between colon cancer predisposition and gut flora, new preventive and therapeutic techniques might be developed. Targeting the gut microbiome with dietary modifications, probiotics, or faecal microbiota transplantation may offer cutting-edge approaches to reducing the risk of colon cancer and improving patient outcomes. The complex connection between the makeup of the gut microbiota and the emergence of colorectal cancer is explored in this narrative review.}, }
@article {pmid39281978, year = {2024}, author = {Zhang, S and Lu, G and Wang, W and Li, Q and Wang, R and Zhang, Z and Wu, X and Liang, C and Liu, Y and Li, P and Wen, Q and Cui, B and Zhang, F}, title = {A predictive machine-learning model for clinical decision-making in washed microbiota transplantation on ulcerative colitis.}, journal = {Computational and structural biotechnology journal}, volume = {24}, number = {}, pages = {583-592}, pmid = {39281978}, issn = {2001-0370}, abstract = {Machine learning based on clinical data and treatment protocols for better clinical decision-making is a current research hotspot. This study aimed to build a machine learning model on washed microbiota transplantation (WMT) for ulcerative colitis (UC), providing patients and clinicians with a new evaluation system to optimize clinical decision-making. Methods Patients with UC who underwent WMT via mid-gut or colonic delivery route at an affiliated hospital of Nanjing Medical University from April 2013 to June 2022 were recruited. Model ensembles based on the clinical indicators were constructed by machine-learning to predict the clinical response of WMT after one month. Results A total of 366 patients were enrolled in this study, with 210 patients allocated for training and internal validation, and 156 patients for external validation. The low level of indirect bilirubin, activated antithrombin III, defecation frequency and cholinesterase and the elderly and high level of creatine kinase, HCO3 [-] and thrombin time were related to the clinical response of WMT at one month. Besides, the voting ensembles exhibited an area under curve (AUC) of 0.769 ± 0.019 [accuracy, 0.754; F1-score, 0.845] in the internal validation; the AUC of the external validation was 0.614 ± 0.017 [accuracy, 0.801; F1-score, 0.887]. Additionally, the model was available at https://wmtpredict.streamlit.app. Conclusions This study pioneered the development of a machine learning model to predict the one-month clinical response of WMT on UC. The findings demonstrate the potential value of machine learning applications in the field of WMT, opening new avenues for personalized treatment strategies in gastrointestinal disorders. Trial registration clinical trials, NCT01790061. Registered 09 February 2013 - Retrospectively registered, https://clinicaltrials.gov/study/NCT01790061.}, }
@article {pmid39281262, year = {2024}, author = {Nagesh, VK and Tran, HH and Elias, D and Kianifar Aguilar, I and Sethi, T and Menon, A and Mansour, C and Furman, F and Tsotsos, K and Subar, T and Auda, A and Sidiqui, A and Lamar, J and Wadhwani, N and Dey, S and Lo, A and Atoot, A and Weissman, S and Sifuentes, H and Bangolo, AI}, title = {Therapeutics involved in managing initial and recurrent Clostridium difficile infection: An updated literature review.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {15}, number = {5}, pages = {95467}, pmid = {39281262}, issn = {2150-5349}, abstract = {Clostridium difficile infection (CDI) has been increasing due to the effect of recurrent hospitalizations. The use of antibiotics has been shown to alter the gut microbiome and lead to CDIs. The treatment is limited to three major antibiotics; however, the incidence of recurrent CDIs has been increasing and drug resistance is a major concern. This aspect is a growing concern in modern medicine especially in the elderly population, critical care patients, and immunocompromised individuals who are at high risk of developing CDIs. Clostridium difficile can lead to various complications including septic shock and fulminant colitis that could prove to be lethal in these patients. Newer modalities of treatment have been developed including bezlotoxumab, a monoclonal antibody and fecal microbiota transplant. There have been studies showing asymptomatic carriers and drug resistance posing a major threat to the healthcare system. Newer treatment options are being studied to treat and prevent CDIs. This review will provide an insight into the current treatment modalities, prevention and newer modalities of treatment and challenges faced in the treatment of CDIs.}, }
@article {pmid39280427, year = {2024}, author = {Lima Barrientos, J and Rojas Huerta, A and Perez Mendoza, A and Abreu Lopez, BA and Salolin Vargas, VP and Garcia Gonzalez, OY and Saldaña Ruiz, MA and Diarte, E and Torijano Sarria, AJ}, title = {The Relationship Between Gut Microbiome and Ophthalmologic Diseases: A Comprehensive Review.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66808}, pmid = {39280427}, issn = {2168-8184}, abstract = {The gut microbiome has been studied in recent years due to its association with various pathological pathways involved in different diseases, caused by its structure, function, and diversity alteration. The knowledge of this mechanism has generated interest in the investigation of its relationship with ophthalmologic diseases. Recent studies infer the existence of a gut-eye microbiota axis, influenced by the intestinal barrier, the blood-retina barrier, and the immune privilege of the eye. A common denominator among ophthalmologic diseases that have been related to this axis is inflammation, which is perpetuated by dysbiosis, causing an alteration of the intestinal barrier leading to increased permeability and, in turn, the release of components such as lipopolysaccharides (LPS), trimethylamine oxide (TMAO), and bacterial translocation. Some theories explain that depending on how the microbiome is composed, a different type of T cells will be activated, while others say that some bacteria can pre-activate T cells that mimic ocular structures and intestinal permeability that allow leakage of metabolites into the circulation. In addition, therapies such as probiotics, diet, and fecal microbiota transplantation (FMT) have been shown to favor the presence of a balanced population of microorganisms that limit inflammation and, in turn, generate a beneficial effect in these eye pathologies. This review aims to analyze how the intestinal microbiome influences various ocular pathologies based on microbial composition and pathological mechanisms, which may provide a better understanding of the diseases and their therapeutic potential.}, }
@article {pmid39280360, year = {2024}, author = {Patibandla, S and Bhatt, N and Lief, S and Beauti, SM and Ansari, AZ}, title = {Gut Microbiota Modulation in the Management of Chronic Obstructive Pulmonary Disease: A Literature Review.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66875}, pmid = {39280360}, issn = {2168-8184}, abstract = {Chronic obstructive pulmonary disease (COPD) represents a significant global health burden, characterized by progressive airflow limitation and exacerbations that significantly impact patient morbidity and mortality. Recent research has investigated the interplay between the gut and the lungs, known as the gut-lung axis, highlighting the role of the gut microbiome in COPD pathogenesis. Dysbiosis, characterized by microbial imbalance, has implications for COPD, influencing disease progression and susceptibility to exacerbations. This comprehensive review integrates current scientific literature on gut microbiota modulation as a therapeutic avenue for COPD management. Through a thorough discussion of studies investigating probiotics, prebiotics, synbiotics, antibiotics, dietary fiber, and fecal microbiota transplantation, this review summarizes the influence of these interventions on COPD via the gut-lung axis through the modulation of systemic inflammation, mucosal immunity, and metabolic processes. The interventions highlighted here show potential in preventing COPD exacerbations, preserving lung function, and improving patient quality of life. By compiling the latest scientific evidence, this review provides a comprehensive framework for physicians and researchers to deduce the effectiveness of gut microbiome modulation as an adjunctive therapeutic strategy in COPD management.}, }
@article {pmid39280189, year = {2024}, author = {Jeyaraman, M and Mariappan, T and Jeyaraman, N and Muthu, S and Ramasubramanian, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Gut microbiome: A revolution in type II diabetes mellitus.}, journal = {World journal of diabetes}, volume = {15}, number = {9}, pages = {1874-1888}, pmid = {39280189}, issn = {1948-9358}, abstract = {Type II diabetes mellitus (T2DM) has experienced a dramatic increase globally across countries of various income levels over the past three decades. The persistent prevalence of T2DM is attributed to a complex interplay of genetic and environmental factors. While numerous pharmaceutical therapies have been developed, there remains an urgent need for innovative treatment approaches that offer effectiveness without significant adverse effects. In this context, the exploration of the gut microbiome presents a promising avenue. Research has increasingly shown that the gut microbiome of individuals with T2DM exhibits distinct differences compared to healthy individuals, suggesting its potential role in the disease's pathogenesis and progression. This emerging field offers diverse applications, particularly in modifying the gut environment through the administration of prebiotics, probiotics, and fecal microbiome transfer. These inter-ventions aim to restore a healthy microbiome balance, which could potentially alleviate or even reverse the metabolic dysfunctions associated with T2DM. Although current results from clinical trials have not yet shown dramatic effects on diabetes management, the groundwork has been laid for deeper investigation. Ongoing and future clinical trials are critical to advancing our understanding of the microbiome's impact on diabetes. By further elucidating the mechanisms through which microbiome alterations influence insulin resistance and glucose metabolism, researchers can develop more targeted interventions. The potential to harness the gut microbiome in developing new therapeutic strategies offers a compelling prospect to transform the treatment landscape of T2DM, potentially reducing the disease's burden significantly with approaches that are less reliant on traditional pharmaceuticals and more focused on holistic, systemic health improvements.}, }
@article {pmid39278946, year = {2024}, author = {Messaoudene, M and Ferreira, S and Saint-Lu, N and Ponce, M and Truntzer, C and Boidot, R and Le Bescop, C and Loppinet, T and Corbel, T and Féger, C and Bertrand, K and Elkrief, A and Isaksen, M and Vitry, F and Sablier-Gallis, F and Andremont, A and Bod, L and Ghiringhelli, F and de Gunzburg, J and Routy, B}, title = {The DAV132 colon-targeted adsorbent does not interfere with plasma concentrations of antibiotics but prevents antibiotic-related dysbiosis: a randomized phase I trial in healthy volunteers.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8083}, pmid = {39278946}, issn = {2041-1723}, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology/administration &amp; dosage/adverse effects ; *Healthy Volunteers ; Animals ; *Dysbiosis/microbiology/chemically induced ; Female ; Mice ; Adult ; Male ; *Gastrointestinal Microbiome/drug effects ; *Colon/microbiology/drug effects ; *Feces/microbiology/chemistry ; Middle Aged ; Fecal Microbiota Transplantation ; Young Adult ; Immune Checkpoint Inhibitors ; }, abstract = {The deleterious impact of antibiotics (ATB) on the microbiome negatively influences immune checkpoint inhibitors (ICI) response in patients with cancer. We conducted a randomized phase I study (EudraCT:2019-A00240-57) with 148 healthy volunteers (HV) to test two doses of DAV132, a colon-targeted adsorbent, alongside intravenous ceftazidime-avibactam (CZA), piperacillin-tazobactam (PTZ) or ceftriaxone (CRO) and a group without ATB. The primary objective of the study was to assess the effect of DAV132 on ATB plasma concentrations and both doses of DAV132 did not alter ATB levels. Secondary objectives included safety, darkening of the feces, and fecal ATB concentrations. DAV132 was well tolerated, with no severe toxicity and similar darkening at both DAV132 doses. DAV132 led to significant decrease in CZA or PTZ feces concentration. When co-administered with CZA or PTZ, DAV132 preserved microbiome diversity, accelerated recovery to baseline composition and protected key commensals. Fecal microbiota transplantation (FMT) in preclinical cancer models in female mice from HV treated with CZA or PTZ alone inhibited anti-PD-1 response, while transplanted samples from HV treated with ATB + DAV132 circumvented resistance to anti-PD-1. This effect was linked to activated CD8[+] T cell populations in the tumor microenvironment. DAV132 represents a promising strategy for overcoming ATB-related dysbiosis and further studies are warranted to evaluate its efficacy in cancer patients.}, }
@article {pmid39277768, year = {2024}, author = {Ma, X and Park, HS and Shin, YJ and Kim, JK and Hong, JK and Han, SW and Yoon, IY and Kim, DH}, title = {The extracellular vesicle of depressive patient-derived Escherichia fergusonii induces vagus nerve-mediated neuroinflammation in mice.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {224}, pmid = {39277768}, issn = {1742-2094}, support = {RS-2024-00344277//the Korea Dementia Research Project/ ; 2017R1A5A2014768//National Research Foundation of Korea/ ; }, mesh = {Animals ; Mice ; *Vagus Nerve/metabolism ; *Extracellular Vesicles/metabolism ; Humans ; Male ; *Neuroinflammatory Diseases/metabolism ; *Depression/metabolism/etiology ; Mice, Inbred C57BL ; Vagotomy ; }, abstract = {BACKGROUND: Gut microbiota dysbiosis is closely associated with psychiatric disorders such as depression and anxiety (DA). In our preliminary study, fecal microbiota transplantation from volunteers with psychological stress and subclinical symptoms of depression (Vsd) induced DA-like behaviors in mice. Escherichia fergusonii (Esf) was found to be more abundant in the feces of Vsd compared to healthy volunteers. Therefore, we investigated the effect of Esf on DA-like behavior and neuroinflammation in mice with and without celiac vagotomy.<br><br>METHODS AND RESULTS: Orally gavaged Esf increased DA-like behaviors, tumor necrosis factor (TNF)-&#x3b1;, and toll-like receptor-4 (TLR4) expression, and NF-&#x3ba;B[+]Iba1[+] and lipopolysaccharide (LPS)[+]Iba1[+] cell populations, while decreasing serotonin, 5-HT1A receptor, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex. However, celiac vagotomy attenuated Esf-induced DA-like behavior and neuroinflammation. Orally gavaged extracellular vesicle (EV) from Vsd feces (vfEV) or Esf culture (esEV) induced DA-like behavior and inflammation in hippocampus, prefrontal cortex and colon. However, celiac vagotomy attenuated vfEV- or esEV-induced DA-like behaviors and inflammation in the brain alone, while vfEV- or esEV-induced blood LPS and TNF-&#x3b1; levels, colonic TNF-&#x3b1; expression and NF-&#x3ba;B-positive cell number, and fecal LPS level were not. Although orally gavaged fluorescence isothiocyanate-labeled esEV was translocated into the blood and hippocampus, celiac vagotomy decreased its translocation into the hippocampus alone.<br><br>CONCLUSIONS: esEVs may be translocated into the brain via the vagus nerve and bloodstream, subsequently inducing TNF-&#x3b1; expression and suppressing serotonin, its receptor, and BDNF expression through the activation of TLR4-mediated NF-&#x3ba;B signaling, thereby contributing to DA pathogenesis.}, }
@article {pmid39277177, year = {2024}, author = {Meng, Q and Zhang, S and Zhang, C and Liu, B and Zhu, W and Wu, L and Zhang, Q and Li, Y and Wang, X and Bian, H}, title = {Disordered gut microbiota in postmenopausal stage amplifies intestinal tight junction damage to accelerate atherosclerosis.}, journal = {Beneficial microbes}, volume = {16}, number = {1}, pages = {67-89}, doi = {10.1163/18762891-bja00036}, pmid = {39277177}, issn = {1876-2891}, mesh = {Animals ; Female ; *Gastrointestinal Microbiome ; *Atherosclerosis/microbiology/pathology/prevention &amp; control ; *Postmenopause ; Humans ; Mice ; Fecal Microbiota Transplantation ; Mice, Knockout ; *Tight Junctions/pathology ; Estrogens/blood ; Receptors, LDL/genetics ; Receptors, Estrogen/metabolism/genetics ; Middle Aged ; Mice, Inbred C57BL ; *Dysbiosis/microbiology ; Disease Models, Animal ; Intestines/pathology/microbiology ; Ovariectomy ; Aorta/pathology ; Intestinal Mucosa/pathology ; }, abstract = {The causes and characteristics of gut microbiota abnormalities and whether microbiota manipulation can prevent atherosclerosis in the postmenopausal stage remain to be determined. Aortic oestrogen receptor expression, histological changes and gut microbiota in women before and after menopause were detected. Serum oestrogen levels, systemic inflammation, intestinal oestrogen receptor expression and histological changes, atherosclerosis, and gut microbiota in low density lipoprotein deletion (LDLR-∕-) female mice before and after ovariectomy were tested. This study examined aortic oestrogen receptor expression, histological changes, and gut microbiota in women before and after menopause, and tested serum oestrogen levels, systemic inflammation, intestinal oestrogen receptor expression, histological changes, atherosclerosis, and gut microbiota in low-density lipoprotein receptor knockout (LDLR-∕-) female mice before and after ovariectomy. We demonstrated that the downregulation of oestrogen and oestrogen receptors after menopause promotes gut microbiota disturbance in both women and female mice. We found that gut microbiota disturbance amplifies the intestinal barrier damage and aggravates systemic inflammation, thereby promoting atherosclerosis in female mice. Faecal microbiota transplantation and antibiotics inhibit the proinflammatory properties of gut microbiota and prevent atherosclerosis by reducing intestinal barrier damage in postmenopausal mice. Together, our study highlights the causes of gut microbiota disturbances and the role of microbiota manipulation in preventing atherosclerosis in postmenopausal stage.}, }
@article {pmid39276451, year = {2024}, author = {Tian, Y and Tian, R and He, J and Guo, Y and Yan, P and Chen, Y and Li, R and Wang, B}, title = {Toralactone alleviates cisplatin-induced acute kidney injury by modulating the gut microbiota-renal axis.}, journal = {International immunopharmacology}, volume = {142}, number = {Pt A}, pages = {113115}, doi = {10.1016/j.intimp.2024.113115}, pmid = {39276451}, issn = {1878-1705}, mesh = {Animals ; *Cisplatin ; *Gastrointestinal Microbiome/drug effects ; *Acute Kidney Injury/chemically induced/drug therapy ; Male ; *Kidney/drug effects/pathology ; *Dysbiosis/chemically induced ; *Mice, Inbred C57BL ; Mice ; *NF-kappa B/metabolism ; *Toll-Like Receptor 4/metabolism/genetics ; Tumor Necrosis Factor-alpha/metabolism/genetics ; Antineoplastic Agents/adverse effects ; Fecal Microbiota Transplantation ; Signal Transduction/drug effects ; Lipopolysaccharides ; Lactones/therapeutic use/pharmacology ; }, abstract = {BACKGROUND: Gut microbiota has been reported to be perturbed by cisplatin and to modulate the nephrotoxicity of chemotherapeutic agents. However, the critical role of toralactone, a bioactive components of Cassia obtusifolia L. seeds, in modulating the gut microbiota in the pathogenesis of cisplatin-induced nephrotoxicity remains to be elucidated.<br><br>METHODS: In this study, we verified the reno-protective effects of toralactone and compared the composition and function of the gut microbiota in the normal, cisplatin-treated and low or high dose of toralactone-treated mice using 16S rDNA gene sequencing. We also investigated the gut microbiota related LPS/TLR4/NF-&#x3ba;B/TNF-&#x3b1; pathway in renal tissue. To elucidate the causal relationship between gut dysbiosis and cisplatin nephrotoxicity, an antibiotic cocktail was administered to deplete the gut microbiota and fecal microbiota transplantation (FMT) was performed prior to cisplatin treatment.<br><br>RESULTS: The renal histopathology showed that toralactone significantly alleviated cisplatin-induced renal injury. 16S rDNA gene sequencing analysis demonstrated that toralactone treatment effectively reversed cisplatin-induced gut microbiota dysbiosis in mice. FMT from toralactone-treated mice to cisplatin-induced kidney injury mice was observed to have the reno-protective effects, and deletion of gut microbiota by antibiotics was found to negate the reno-protective effect of toralactone. Interestingly, the renal tissue of cisplatin-associated kidney injury mice showed activation of the LPS/TLR4/NF-&#x3ba;B pathway and increase in TNF-&#x3b1; within the renal tissue, whereas toralactone treatment was observed to inhibit the LPS/TLR4/NF-&#x3ba;B/TNF-&#x3b1; pathway.<br><br>CONCLUSION: This study elucidated the reno-protective effects for the first time, demonstrating that it exerts its beneficial effects through the gut microbiota, which mediate the LPS/TLR4/NF-&#x3ba;B/TNF-&#x3b1; inflammatory pathway. It may help to develop therapeutic approaches using toralactone and targeted restoration of the gut microbiota.}, }
@article {pmid39276368, year = {2024}, author = {Čížková, D and Payne, P and Bryjová, A and Ďureje, &#x13d; and Piálek, J and Kreisinger, J}, title = {Convergence of gut phage communities but not bacterial communities following wild mouse bacteriophage transplantation into captive house mice.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {39276368}, issn = {1751-7370}, support = {19-19307S//Czech Science Foundation/ ; e-INFRA CZ LM2018140//Ministry of Education, Youth, and Sports of the Czech Republic/ ; }, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Bacteriophages/isolation &amp; purification/genetics/physiology ; Bacteria/classification/virology/genetics/isolation &amp; purification ; Animals, Wild/microbiology ; Specific Pathogen-Free Organisms ; Feces/microbiology/virology ; Female ; Virome ; }, abstract = {Bacteriophages are abundant components of vertebrate gut microbial communities, impacting bacteriome dynamics, evolution, and directly interacting with the superhost. However, knowledge about gut phageomes and their interaction with bacteriomes in vertebrates under natural conditions is limited to humans and non-human primates. Widely used specific-pathogen-free (SPF) mouse models of host-microbiota interactions have altered gut bacteriomes compared to wild mice, and data on phageomes from wild or other non-SPF mice are lacking. We demonstrate divergent gut phageomes and bacteriomes in wild and captive non-SPF mice, with wild mice phageomes exhibiting higher alpha-diversity and interindividual variability. In both groups, phageome and bacteriome structuring mirrored each other, correlating at the individual level. Re-analysis of previous data from phageomes of SPF mice revealed their enrichment in Suoliviridae crAss-like phages compared to our non-SPF mice. Disrupted bacteriomes in mouse models can be treated by transplanting healthy phageomes, but the effects of phageome transplants on healthy adult gut microbiota are still unknown. We show that experimental transplantation of phageomes from wild to captive mice did not cause major shifts in recipient phageomes. However, the convergence of recipient-to-donor phageomes confirmed that wild phages can integrate into recipient communities. The differences in the subset of integrated phages between the two recipient mouse strains illustrate the context-dependent effects of phage transplantation. The transplantation did not impact recipient gut bacteriomes. This resilience of healthy adult gut microbiomes to the intervention has implications for phage allotransplantation safety.}, }
@article {pmid39267518, year = {2024}, author = {Gan, Y and Wu, ZH and Li, QL and Lu, ZX and Chen, LL}, title = {[Advances in the treatment of Clostridium difficile infection in children].}, journal = {Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics}, volume = {26}, number = {9}, pages = {995-1001}, pmid = {39267518}, issn = {1008-8830}, mesh = {Humans ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Child ; Clostridioides difficile ; Risk Factors ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Clostridium difficile infection (CDI) is a major cause of hospital-acquired gastrointestinal infections in children. Current treatment for pediatric CDI primarily involves antibiotics; however, some children experience recurrence after antibiotic treatment, and those with initial recurrence remain at risk for further recurrences following subsequent antibiotic therapy. In such cases, careful consideration of treatment options is necessary. Fecal microbiota transplantation has been shown to be effective for recurrent CDI and has a high safety profile. This article reviews the latest research on the pathogenesis, risk factors, diagnosis, and treatment of pediatric CDI domestically and internationally, with a particular focus on fecal microbiota transplantation therapy.}, }
@article {pmid39267235, year = {2024}, author = {}, title = {Correction to "Long-Term Effects of Fecal Microbiota Transplantation on Gut Microbiota After Helicobacter pylori Eradication With Bismuth Quadruple Therapy: A Randomized Controlled Trial".}, journal = {Helicobacter}, volume = {29}, number = {5}, pages = {e13127}, doi = {10.1111/hel.13127}, pmid = {39267235}, issn = {1523-5378}, }
@article {pmid39273662, year = {2024}, author = {Acevedo-Román, A and Pagán-Zayas, N and Velázquez-Rivera, LI and Torres-Ventura, AC and Godoy-Vitorino, F}, title = {Insights into Gut Dysbiosis: Inflammatory Diseases, Obesity, and Restoration Approaches.}, journal = {International journal of molecular sciences}, volume = {25}, number = {17}, pages = {}, pmid = {39273662}, issn = {1422-0067}, support = {P20 GM103475/GM/NIGMS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; U54 MD007600//MD/NIMHD NIH HHS/United States ; S21 MD001830/MD/NIMHD NIH HHS/United States ; T32 GM148406/GM/NIGMS NIH HHS/United States ; U54 MD007600/MD/NIMHD NIH HHS/United States ; }, mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *Gastrointestinal Microbiome ; *Obesity/microbiology ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Animals ; Inflammation/microbiology ; Prebiotics/administration &amp; dosage ; }, abstract = {The gut microbiota is one of the most critical factors in human health. It involves numerous physiological processes impacting host health, mainly via immune system modulation. A balanced microbiome contributes to the gut's barrier function, preventing the invasion of pathogens and maintaining the integrity of the gut lining. Dysbiosis, or an imbalance in the gut microbiome's composition and function, disrupts essential processes and contributes to various diseases. This narrative review summarizes key findings related to the gut microbiota in modern multifactorial inflammatory conditions such as ulcerative colitis or Crohn's disease. It addresses the challenges posed by antibiotic-driven dysbiosis, particularly in the context of C. difficile infections, and the development of novel therapies like fecal microbiota transplantation and biotherapeutic drugs to combat these infections. An emphasis is given to restoration of the healthy gut microbiome through dietary interventions, probiotics, prebiotics, and novel approaches for managing gut-related diseases.}, }
@article {pmid39272235, year = {2024}, author = {Li, H and Han, L and Zhou, F and Wu, Z and Zhang, L and Xie, R and Jiang, F and Tian, Q and Huang, X}, title = {Ningxiang Pig-Derived Microbiota Affects the Growth Performance, Gut Microbiota, and Serum Metabolome of Nursery Pigs.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {17}, pages = {}, pmid = {39272235}, issn = {2076-2615}, support = {U20A2055//National Natural Science Foundation of China/ ; }, abstract = {The gut microbiota is crucial for maintaining the host's intestinal homeostasis and metabolism. This study investigated the effects of fecal microbiota transplantation (FMT) from Ningxiang pigs on the growth performance, fecal microbiota, and serum metabolites of the same-old DLY pigs. The results indicated that the average daily gain of FMT pigs was significantly greater than that of the control (CON) group. Compared to the CON group, the FMT group significantly improved the apparent digestibility of crude fiber, crude ash, gross energy, and calcium of the pigs. The analysis of serum antioxidant status revealed that the activities of total superoxide dismutase and catalase in the serum of pigs in the FMT group were significantly elevated, whereas the level of malondialdehyde was significantly reduced. Furthermore, 16S rRNA sequencing analysis revealed that the Ningxiang pig-derived microbiota altered the fecal microbiota structure and modulated the diversity of the gut microbiota in the DLY pigs. Untargeted LC-MS metabolomics demonstrated that pigs in the FMT group exhibited distinct metabolomic profiles compared to those in the CON group. Significant changes were observed in key metabolites involved in amino acid, lipid, and carbohydrate metabolism. Additionally, a correlation analysis between serum differential metabolites and the gut microbiota revealed that the relative abundance of Lachnospiraceae_NK4A136_group and Corynebacterium was highly correlated with lipid compounds. In conclusion, Ningxiang pig-derived microbiota can alleviate oxidative stress and enhance growth performance in DLY pigs by modulating their gut microbiota and metabolic features.}, }
@article {pmid39271443, year = {2025}, author = {López Zúñiga, M&#xc1; and Sánchez Cabello, A and López Ruz, M&#xc1;}, title = {Diagnostic and therapeutic management of Clostridioides difficile infection.}, journal = {Medicina clinica}, volume = {164}, number = {3}, pages = {136-142}, doi = {10.1016/j.medcli.2024.06.004}, pmid = {39271443}, issn = {1578-8989}, mesh = {Humans ; *Clostridioides difficile/isolation &amp; purification/genetics/enzymology ; *Clostridium Infections/diagnosis/therapy/drug therapy ; Algorithms ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Feces/microbiology ; Broadly Neutralizing Antibodies ; Fidaxomicin/therapeutic use ; Metronidazole/therapeutic use ; Antibodies, Monoclonal ; }, abstract = {A review of the diagnostic and therapeutic management algorithm of the pathogen Clostridioides difficile for daily practice is presented. Its diagnosis, in any unformed stool sample sent to the laboratory, is based on a two-step algorithm, with demonstration of the pathogen by means of its enzyme glutamate dehydrogenase by immunoassay and subsequent PCR (polymerase chain reaction) of its toxin. The mainstay of step therapy, reserved for symptomatic patients, is fidaxomicin, over vancomycin. Metronidazole is not an adequate treatment. Emerging therapies, such as faecal microbiota transplantation or the antibody bezlotoxumab, are gaining importance in patients with risk factors or relapses. Surgery is indicated in patients with worse prognosis and complications. Prevention is essential, based on vigilance and contact precautions, in addition to the elimination of spores from the environment.}, }
@article {pmid39271107, year = {2025}, author = {Drekonja, DM and Shaukat, A and Huang, Y and Zhang, JH and Reinink, AR and Nugent, S and Dominitz, JA and Davis-Karim, A and Gerding, DN and Kyriakides, TC}, title = {A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {80}, number = {1}, pages = {52-60}, doi = {10.1093/cid/ciae467}, pmid = {39271107}, issn = {1537-6591}, support = {//Cooperative Studies Program of the VA Office of Research and Development/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Clostridium Infections/prevention &amp; control/therapy ; Male ; Female ; Double-Blind Method ; Aged ; Middle Aged ; Clostridioides difficile ; Recurrence ; Diarrhea/therapy/microbiology ; Treatment Outcome ; Secondary Prevention ; Feces/microbiology ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infections in US hospitals, with 15%-30% of patients experiencing recurrence. The aim of our randomized, double-blind clinical trial was to assess the efficacy of capsule-delivered fecal microbiota transplant (FMT) versus placebo in reducing recurrent diarrhea and CDI recurrence. The secondary aim was FMT safety assessment.<br><br>METHODS: Between 2018 and 2022, Veterans across the Veterans Health Administration system with recurrent CDI who responded to antibiotic treatment were randomized in a 1:1 ratio to oral FMT or placebo capsules. Randomization was stratified by number of prior CDI recurrences (1 or &#x2265;2). The primary endpoint was clinical recurrence by day 56, defined as >3 unformed stools daily for &#x2265;2 days with or without laboratory confirmation of C. difficile, or death within 56 days.<br><br>RESULTS: The study was stopped due to futility after meeting prespecified criteria. Of 153 participants (76 FMT, 77 placebo) with an average age of 66.5 years, 25 participants (32.9%) in the FMT arm and 23 (29.9%) in the placebo arm experienced the primary endpoint of diarrhea and possible or definite CDI recurrence or death within 56 days of capsule administration (absolute difference, 3.0% [95% confidence interval, -11.7% to 17.7%]). Stratification by number of recurrences revealed no statistically significant differences. There were no clinically important differences in adverse events.<br><br>CONCLUSIONS: FMT therapy versus placebo did not reduce CDI recurrence or death at 56 days. There were no meaningful differences in adverse events between treatment groups.<br><br>CLINICAL TRIALS REGISTRATION: NCT03005379.}, }
@article {pmid39270883, year = {2025}, author = {Li, F and Han, Q and Cai, Y and Li, Y and Yang, Y and Li, J and Wu, R and Chen, R and Liu, R}, title = {Si-Ni-San ameliorates cholestatic liver injury by favoring P. goldsteinii colonization.}, journal = {Journal of ethnopharmacology}, volume = {337}, number = {Pt 1}, pages = {118804}, doi = {10.1016/j.jep.2024.118804}, pmid = {39270883}, issn = {1872-7573}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Cholestasis/drug therapy ; Male ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Dysbiosis/drug therapy ; *Mice, Inbred C57BL ; Mice ; Liver/drug effects/metabolism/pathology ; Fecal Microbiota Transplantation ; Disease Models, Animal ; }, abstract = {Current treatment options for cholestatic liver diseases are limited, and addressing impaired intestinal barrier has emerged as a promising therapeutic approach. Si-Ni-San (SNS) is a Traditional Chinese Medicine (TCM) formula commonly utilized in the management of chronic liver diseases. Our previous studies have indicated that SNS effectively enhanced intestinal barrier function through the modulation of gut microbiota.<br><br>AIM OF THE STUDY: This study aims to verify the therapeutic effects of SNS on cholestatic liver injury, focusing on elucidating the underlying mechanism involving the gut-liver axis.<br><br>MATERIALS AND METHODS: The 16s RNA gene sequencing, non-targeted metabolomics were used to investigate the effects of SNS on the gut microbiota dysbiosis. Fecal microbiota transplantation (FMT) was conducted to identify potential beneficial probiotics underlying the therapeutic effects of SNS.<br><br>RESULTS: Our results demonstrated that SNS significantly ameliorated cholestatic liver injury induced by partial bile duct ligation (pBDL). Additionally, SNS effectively suppressed cholestasis-induced inflammation and barrier dysfunction in both the small intestine and colon. While SNS did not impact the intestinal FXR-FGF15-hepatic CYP7A1 axis, it notably improved gut microbiota dysbiosis and modulated the profile of microbial metabolites, including beneficial secondary bile acids and tryptophan derivatives. Furthermore, gut microbiota depletion experiments and FMT confirmed that the therapeutic benefits of SNS in cholestatic liver disease are dependent on gut microbiota modulation, particularly through the promotion of the growth of potential probiotic P. goldsteinii. Moreover, a synergistic improvement in cholestatic liver injury was observed with the co-administration of P. goldsteinii and SNS.<br><br>CONCLUSION: Our study underscores that SNS effectively alleviates cholestatic liver injury by addressing gut microbiota dysbiosis and enhancing intestinal barrier function, supporting its rational clinical utilization. Furthermore, we highlight P. goldsteinii as a promising probiotic candidate for the management of cholestatic liver diseases.}, }
@article {pmid39270730, year = {2025}, author = {Poutanen, SM and Hota, SS}, title = {Déjà Vu: Unanswered Questions About Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {80}, number = {1}, pages = {61-62}, doi = {10.1093/cid/ciae468}, pmid = {39270730}, issn = {1537-6591}, }
@article {pmid39269772, year = {2024}, author = {Rahal, Z and Liu, Y and Peng, F and Yang, S and Jamal, MA and Sharma, M and Moreno, H and Damania, AV and Wong, MC and Ross, MC and Sinjab, A and Zhou, T and Chen, M and Tarifa Reischle, I and Feng, J and Chukwuocha, C and Tang, E and Abaya, C and Lim, JK and Leung, CH and Lin, HY and Deboever, N and Lee, JJ and Sepesi, B and Gibbons, DL and Wargo, JA and Fujimoto, J and Wang, L and Petrosino, JF and Ajami, NJ and Jenq, RR and Moghaddam, SJ and Cascone, T and Hoffman, K and Kadara, H}, title = {Inflammation Mediated by Gut Microbiome Alterations Promotes Lung Cancer Development and an Immunosuppressed Tumor Microenvironment.}, journal = {Cancer immunology research}, volume = {12}, number = {12}, pages = {1736-1752}, pmid = {39269772}, issn = {2326-6074}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA205608/CA/NCI NIH HHS/United States ; P30 ES030285/ES/NIEHS NIH HHS/United States ; S10 OD024977/OD/NIH HHS/United States ; R01CA248731//National Cancer Institute (NCI)/ ; R01 CA248731/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; *Tumor Microenvironment/immunology ; *Lung Neoplasms/immunology/microbiology/pathology ; Mice ; Humans ; *Inflammation/immunology ; Adenocarcinoma of Lung/immunology/microbiology/pathology ; Lipocalin-2/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Mice, Knockout ; }, abstract = {Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely coupled with tobacco-associated lung adenocarcinoma in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimicrobial protein Lcn2 in these mice exacerbates protumor inflammatory phenotypes while further reducing microbial diversity. Yet, how gut microbiome alterations impinge on lung adenocarcinoma development remains poorly understood. In this study, we investigated the role of gut microbiome changes in lung adenocarcinoma development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations incurred by loss of Lcn2 fostered the proliferation of proinflammatory bacteria of the genus Alistipes, triggering gut inflammation. This inflammation propagated systemically, exerting immunosuppression within the tumor microenvironment, augmenting tumor growth through an IL6-dependent mechanism and dampening response to immunotherapy. Corroborating our preclinical findings, we found that patients with lung adenocarcinoma with a higher relative abundance of Alistipes species in the gut showed diminished response to neoadjuvant immunotherapy. These insights reveal the role of microbiome-induced inflammation in lung adenocarcinoma and present new potential targets for interception and therapy.}, }
@article {pmid39269473, year = {2024}, author = {Singh, V and Choi, SD and Mahra, K and Son, H and Lee, H and Lee, YJ and Kim, ES and Shin, JH}, title = {Cultured fecal microbial community and its impact as fecal microbiota transplantation treatment in mice gut inflammation.}, journal = {Applied microbiology and biotechnology}, volume = {108}, number = {1}, pages = {463}, pmid = {39269473}, issn = {1432-0614}, support = {2021R1A6C101A416//Korea Basic Science Institute/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Animals ; *Feces/microbiology ; Mice ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Disease Models, Animal ; *Cytokines/metabolism ; *RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; Dextran Sulfate ; Male ; Culture Media/chemistry ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {The fecal microbiome is identical to the gut microbial communities and provides an easy access to the gut microbiome. Therefore, fecal microbial transplantation (FMT) strategies have been used to alter dysbiotic gut microbiomes with healthy fecal microbiota, successfully alleviating various metabolic disorders, such as obesity, type 2 diabetes, and inflammatory bowel disease (IBD). However, the success of FMT treatment is donor-dependent and variations in gut microbes cannot be avoided. This problem may be overcome by using a cultured fecal microbiome. In this study, a human fecal microbiome was cultured using five different media; growth in brain heart infusion (BHI) media resulted in the highest microbial community cell count. The microbiome (16S rRNA) data demonstrated that the cultured microbial communities were similar to that of the original fecal sample. Therefore, the BHI-cultured fecal microbiome was selected for cultured FMT (cFMT). Furthermore, a dextran sodium sulfate (DSS)-induced mice-IBD model was used to confirm the impact of cFMT. Results showed that cFMT effectively alleviated IBD-associated symptoms, including improved gut permeability, restoration of the inflamed gut epithelium, decreased expression of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1, IL-6, IL-12, and IL-17), and increased expression of anti-inflammatory cytokines (IL-4 and IL-10). Thus, study's findings suggest that cFMT can be a potential alternative to nFMT. KEY POINTS: • In vitro fecal microbial communities were grown in a batch culture using five different media. • Fecal microbial transplantation was performed on DSS-treated mice using cultured and normal fecal microbes. • Cultured fecal microbes effectively alleviated IBD-associated symptoms.}, }
@article {pmid39267080, year = {2024}, author = {Wei, X and Xing, F and Xu, Y and Zhang, F and Cheng, D and Zhou, Y and Zheng, F and Zhang, W}, title = {Preoperative gut microbiota of POCD patients induces pre- and postoperative cognitive impairment and systemic inflammation in rats.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {221}, pmid = {39267080}, issn = {1742-2094}, support = {82002086//National Natural Science Foundation of China/ ; 82001187//National Natural Science Foundation of China/ ; 82071240//National Natural Science Foundation of China/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Rats ; *Postoperative Cognitive Complications/etiology ; Male ; Humans ; Female ; Aged ; *Inflammation ; Rats, Sprague-Dawley ; Middle Aged ; Retrospective Studies ; Cognitive Dysfunction/etiology/microbiology ; }, abstract = {BACKGROUND: Postoperative cognitive dysfunction (POCD) is common following surgery in elderly patients. The role of the preoperative gut microbiota in POCD has attracted increasing attention, but the potential underlying mechanisms remain unclear. This research aimed to investigate the impact of the preoperative gut microbiota on POCD.<br><br>METHODS: Herein, we analyzed the preoperative gut microbiota of POCD patients through a prospective specimen collection and retrospective blinded evaluation study. Then, we transferred the preoperative gut microbiota of POCD patients to antibiotic-treated rats and established POCD model by abdominal surgery to explore the impact of the preoperative gut microbiota on pre- and postoperative cognitive function and systemic inflammation. The gut microbiota was analyzed using 16S rRNA sequencing analysis. The Morris water maze test was performed to evaluate learning and memory abilities. The inflammatory cytokines TNF-&#x3b1;, IL-1&#x3b2; and IL-6 in the serum and hippocampus were measured by ELISA. Microglia were examined by immunofluorescence staining for Iba-1.<br><br>RESULTS: Based on the decrease in the postoperative MMSE score, 24 patients were identified as having POCD and were matched with 24 control patients. Compared with control patients, POCD patients exhibited higher BMI and lower preoperative MMSE score. The preoperative gut microbiota of POCD patients had lower bacterial richness but a larger distribution, decreased abundance of Firmicutes and increased abundance of Proteobacteria than did that of control patients. Compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of&#xa0;POCD patients presented an increased abundance of Desulfobacterota, decreased cognitive function, increased levels of TNF-&#x3b1; and IL-1&#x3b2; in the serum, increased levels of TNF-&#x3b1; and greater microglial activation in the hippocampus. Additionally, correlation analysis revealed a positive association between the abundance of Desulfobacterota and the level of serum TNF-&#x3b1; in rats. Then, we performed abdominal surgery to investigate the impact of the preoperative gut microbiota on postoperative conditions, and the surgery did indeed cause POCD and inflammatory response. Notably, compared with rats that received preoperative fecal samples of&#xa0;control patients, rats that received preoperative fecal samples of POCD patients displayed exacerbated cognitive impairment; increased levels of TNF-&#x3b1;, IL-1&#x3b2; and IL-6 in the serum and hippocampus; and increased activation of microglia in the hippocampus.<br><br>CONCLUSIONS: Our findings suggest that the preoperative gut microbiota of POCD patients can induce preoperative and aggravate postoperative cognitive impairment and systemic inflammation in rats. Modulating inflammation by targeting the gut microbiota might be a promising approach for preventing POCD.}, }
@article {pmid39266472, year = {2024}, author = {Bell, J and Radial, SL and Cuming, RS and Trope, G and Hughes, KJ}, title = {Effects of fecal microbiota transplantation on clinical outcomes and fecal microbiota of foals with diarrhea.}, journal = {Journal of veterinary internal medicine}, volume = {38}, number = {5}, pages = {2718-2728}, pmid = {39266472}, issn = {1939-1676}, support = {//Agrifutures Australia/ ; }, mesh = {Animals ; Horses ; *Diarrhea/veterinary/therapy/microbiology ; *Fecal Microbiota Transplantation/veterinary ; *Horse Diseases/therapy/microbiology ; Female ; *Feces/microbiology ; Male ; Gastrointestinal Microbiome ; Prospective Studies ; Treatment Outcome ; Animals, Newborn ; Dysbiosis/veterinary/therapy ; Cohort Studies ; }, abstract = {BACKGROUND: Diarrhea in foals can be associated with disruption of the intestinal microbiota (dysbiosis). Effective management of intestinal dysbiosis in foals has not been demonstrated.<br><br>HYPOTHESIS/OBJECTIVES: Fecal microbiota transplantation (FMT) in foals with diarrhea influences the intestinal microbiota and improves clinical and clinicopathological outcomes.<br><br>ANIMALS: Twenty-five foals <6&#x2009;months of age with diarrhea and systemic inflammatory response syndrome at 3 veterinary hospitals.<br><br>METHODS: A prospective randomized placebo-controlled cohort study. Foals in the FMT group (n&#x2009;=&#x2009;19) or control group (n&#x2009;=&#x2009;9) received FMT or electrolyte solution once daily for 3&#x2009;days. Fecal samples were obtained on Day 0 (D0), D1, D2, D3, and D7. Within group and between group data analyses were performed for clinical, clinicopathological, and microbiota variables.<br><br>RESULTS: Treatment had no effect on survival (FMT 79%; control 100%, P&#x2009;=&#x2009;.3) or resolution of diarrhea (FMT 68%; control 55%, P&#x2009;=&#x2009;.4). On D3, the white blood cell count of the FMT group was lower than the control group (D3 FMT group median 6.4&#x2009;g/L [5-8.3&#x2009;g/L]; D3 control group median 14.3&#x2009;g/L [6.7-18.9&#x2009;g/L] P&#x2009;=&#x2009;.04). Heart rate reduced over time in the FMT group (D0 median 80&#x2009;bpm [60-150&#x2009;bpm]; D2 median 70&#x2009;bpm [52-110&#x2009;bpm] [P&#x2009;=&#x2009;.005]; and D3 median 64, [54-102&#x2009;bpm] [P&#x2009;<&#x2009;.001]). Phylum Verrucomicrobiota, genus Akkermansia, and family Prevotellaceae were enriched in the FMT group on D1 (linear discriminate analysis&#x2009;>&#x2009;4).<br><br>In foals with diarrhea, FMT appears safe and can be associated with some clinical and microbiota changes suggestive of beneficial effect.}, }
@article {pmid39265742, year = {2025}, author = {Herner, A and Nennstiel, S and Ramser, M and Turina, M and Schlag, C}, title = {New therapeutic approach for anastomotic leaks after ileoanal J-pouch construction in patients with ulcerative colitis.}, journal = {Gastrointestinal endoscopy}, volume = {101}, number = {1}, pages = {222-223}, doi = {10.1016/j.gie.2024.09.004}, pmid = {39265742}, issn = {1097-6779}, }
@article {pmid39263354, year = {2024}, author = {Zhang, C and Wang, G and Yin, X and Gou, L and Guo, M and Suo, F and Zhuang, T and Yuan, Z and Liu, Y and Gu, M and Yao, R}, title = {Hepatic protein phosphatase 1 regulatory subunit 3G alleviates obesity and liver steatosis by regulating the gut microbiota and bile acid metabolism.}, journal = {Journal of pharmaceutical analysis}, volume = {14}, number = {8}, pages = {100976}, pmid = {39263354}, issn = {2214-0883}, abstract = {Intestinal dysbiosis and disrupted bile acid (BA) homeostasis are associated with obesity, but the precise mechanisms remain insufficiently explored. Hepatic protein phosphatase 1 regulatory subunit 3G (PPP1R3G) plays a pivotal role in regulating glycolipid metabolism; nevertheless, its obesity-combatting potency remains unclear. In this study, a substantial reduction was observed in serum PPP1R3G levels in high-body mass index (BMI) and high-fat diet (HFD)-exposed mice, establishing a positive correlation between PPP1R3G and non-12α-hydroxylated (non-12-OH) BA content. Additionally, hepatocyte-specific overexpression of Ppp1r3g (PPP1R3G HOE) mitigated HFD-induced obesity as evidenced by reduced weight, fat mass, and an improved serum lipid profile; hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology. PPP1R3G HOE considerably impacted systemic BA homeostasis, which notably increased the non-12-OH BAs ratio, particularly lithocholic acid (LCA). 16S ribosomal DNA (16S rDNA) sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population, and elevating the relative abundance of Blautia, which exhibited a positive correlation with serum LCA levels. A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent. Mechanistically, PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase (CYP7A1) and sterol-12α-hydroxylase (CYP8B1), and concurrently upregulated oxysterol 7-α hydroxylase and G protein-coupled BA receptor 5 (TGR5) expression under HFD conditions. Furthermore, LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels. These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis, which may serve as potential therapeutic targets for obesity-related disorders.}, }
@article {pmid39262376, year = {2024}, author = {Wang, T and Hao, L and Yang, K and Feng, W and Guo, Z and Liu, M and Xiao, R}, title = {Fecal microbiota transplantation derived from mild cognitive impairment individuals impairs cerebral glucose uptake and cognitive function in wild-type mice: Bacteroidetes and TXNIP-GLUT signaling pathway.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2395907}, pmid = {39262376}, issn = {1949-0984}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Cognitive Dysfunction/metabolism/microbiology ; Mice ; *Gastrointestinal Microbiome ; *Glucose/metabolism ; *Brain/metabolism ; *Bacteroidetes/metabolism ; *Signal Transduction ; *Dysbiosis/microbiology/metabolism ; Male ; Humans ; *Cognition ; Mice, Inbred C57BL ; Carrier Proteins/metabolism/genetics ; Glucose Transport Proteins, Facilitative/metabolism/genetics ; Thioredoxins ; }, abstract = {Gut microbiome dysbiosis has been widely implicated in cognitive impairment, but the identity of the specific bacterial taxa and mechanisms are not fully elucidated. Brain glucose hypometabolism coincides with the cognitive decline. This study explored the link among cognition, gut microbiota and glucose uptake based on the fecal microbiota transplantation from mild cognitive impairment individuals (MCI-FMT) and investigated whether similar mechanisms were involved in 27-hydroxycholesterol (27-OHC)-induced cognitive decline. Our results showed that the MCI-FMT mice exhibited learning and memory decline and morphological lesions in the brain and colon tissues. There were reduced [18]F-fluorodeoxyglucose uptake, downregulated expression of glucose transporters (GLUT1,3,4) and upregulated negative regulator of glucose uptake (TXNIP) in the brain. MCI-FMT altered the bacterial composition and diversity of the recipient mice, and the microbial signatures highlighted by the increased abundance of Bacteroides recapitulated the negative effects of MCI bacterial colonization. However, inhibiting Bacteroidetes or TXNIP increased the expression of GLUT1 and GLUT4, significantly improving brain glucose uptake and cognitive performance in 27-OHC-treated mice. Our study verified that cognitive decline and abnormal cerebral glucose uptake were associated with gut microbiota dysbiosis; we also revealed the involvement of Bacteroidetes and molecular mechanisms of TXNIP-related glucose uptake in cognitive deficits caused by 27-OHC.}, }
@article {pmid39262248, year = {2024}, author = {Mu, X and Zhang, J and Li, H and Li, H and Mu, Z and Ye, F and Li, J and Ye, F}, title = {Effects of intestinal flora on cerebral hemorrhage area and brain tissue inflammation in acute hemorrhagic stroke.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {70}, number = {8}, pages = {153-157}, doi = {10.14715/cmb/2024.70.8.21}, pmid = {39262248}, issn = {1165-158X}, mesh = {Animals ; Male ; *Cerebral Hemorrhage/complications/pathology/microbiology/metabolism ; *Mice, Inbred C57BL ; *Gastrointestinal Microbiome ; *Hemorrhagic Stroke/pathology/metabolism ; *Brain/pathology/metabolism ; Inflammation/pathology/metabolism ; Disease Models, Animal ; Mice ; Brain Edema/pathology/metabolism ; Hematoma/pathology/metabolism/complications ; }, abstract = {To explore the impacts of intestinal flora on cerebral hemorrhage area and brain tissue inflammation in acute hemorrhagic stroke, seventy-two male C57BL/6 mice were randomly separated into 6 groups (n=12), the experimental group (EG, day 1, day 3 and day 7) and the control group (CG, day 1, day 3 and day 7). The mouse cerebral hemorrhage model was established by collagenase injection, and the EG received 0.4 mL fecal filtrate of healthy mice once a day, and the CG received the same amount of normal saline transplantation. The mNSS score, hematoma volume and cerebral edema content were used to evaluate nerve function injury and brain injury degree at each time point after operation. The expressions of inflammatory factors were detected by western blot. We found that at each time point after operation, compared with the CG, nerve function deficit scores of mice in the EG declined (P<0.05), the water content of mice brain tissue in the EG declined (P<0.05), and the protein expressions of inflammatory factors in the EG were decreased (P<0.05). Relative to the CG, the volume of hematoma in the EG declined on day 3 along with day 7 after operation (P<0.05). In conclusion, intestinal flora can reduce cerebral hemorrhage area and brain tissue inflammation, and then improve the performance of nerve function deficit in acute hemorrhagic stroke.}, }
@article {pmid39261424, year = {2024}, author = {Evrensel, A}, title = {Probiotics and Fecal Microbiota Transplantation in Major Depression: Doxa or Episteme?.}, journal = {Advances in experimental medicine and biology}, volume = {1456}, number = {}, pages = {67-83}, pmid = {39261424}, issn = {0065-2598}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; *Depressive Disorder, Major/therapy/microbiology ; Antidepressive Agents/therapeutic use ; Animals ; }, abstract = {In the human body, eukaryotic somatic cells and prokaryotic microorganisms live together. In this state, the body can be viewed as a "superorganism." Symbiotic life with commensal microorganisms can be observed in almost every part of the body. Intestinal microbiota plays an important role in health and disease, and in shaping and regulating neuronal functions from the intrauterine period to the end of life. Microbiota-based treatment opportunities are becoming more evident in both understanding the etiopathogenesis and treatment of neuropsychiatric disorders, especially depression. Antidepressant drugs, which are the first choice in the treatment of depression, also have antimicrobial and immunomodulatory mechanisms of action. From these perspectives, direct probiotics and fecal microbiota transplantation are treatment options to modulate microbiota composition. There are few preclinical and clinical studies on the effectiveness and safety of these applications in depression. The information obtained from these studies may still be at a doxa level. However, the probability that this information will become episteme in the future seems to be increasing.}, }
@article {pmid39259805, year = {2024}, author = {Sawaed, J and Zelik, L and Levin, Y and Feeney, R and Naama, M and Gordon, A and Zigdon, M and Rubin, E and Telpaz, S and Modilevsky, S and Ben-Simon, S and Awad, A and Harshuk-Shabso, S and Nuriel-Ohayon, M and Werbner, M and Schroeder, BO and Erez, A and Bel, S}, title = {Antibiotics damage the colonic mucus barrier in a microbiota-independent manner.}, journal = {Science advances}, volume = {10}, number = {37}, pages = {eadp4119}, pmid = {39259805}, issn = {2375-2548}, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology/adverse effects ; Mice ; *Intestinal Mucosa/metabolism/microbiology/drug effects/pathology ; *Gastrointestinal Microbiome/drug effects ; *Colon/metabolism/drug effects/pathology/microbiology ; *Mucus/metabolism ; Inflammatory Bowel Diseases/chemically induced/metabolism/pathology/microbiology ; Endoplasmic Reticulum Stress/drug effects ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Humans ; }, abstract = {Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not separate the intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics affect the integrity of the mucus barrier, which allows bacterial penetrance and predisposes to intestinal inflammation. We found that antibiotic treatment led to breakdown of the colonic mucus barrier and penetration of bacteria into the mucus layer. Using fecal microbiota transplant, RNA sequencing followed by machine learning, ex vivo mucus secretion measurements, and antibiotic treatment of germ-free mice, we determined that antibiotics induce endoplasmic reticulum stress in the colon that inhibits colonic mucus secretion in a microbiota-independent manner. This antibiotic-induced mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation, and exacerbation of ulcerations in a mouse model of IBD. Thus, antibiotic use might predispose to intestinal inflammation by impeding mucus production.}, }
@article {pmid39256134, year = {2024}, author = {Sono, M and Iimori, K and Nagao, M and Ogawa, S and Maruno, T and Nakanishi, Y and Anazawa, T and Nagai, K and Masui, T and Mori, H and Hosomi, K and Kunisawa, J and Yokota, H and Tanaka, Y and Ohno, H and Hatano, E and Fukuda, A and Seno, H}, title = {Reduction of butyrate-producing bacteria in the gut microbiome of Japanese patients with pancreatic cancer.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {24}, number = {7}, pages = {1031-1039}, doi = {10.1016/j.pan.2024.09.002}, pmid = {39256134}, issn = {1424-3911}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Bacteria/genetics/classification/isolation &amp; purification ; *Butyrates/metabolism ; Case-Control Studies ; East Asian People ; Feces/microbiology ; *Gastrointestinal Microbiome ; Japan ; Mouth/microbiology ; *Pancreatic Neoplasms/microbiology ; *RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The incidence of pancreatic cancer is on the rise, and its prognosis remains poor. Recent reports have established a link between the gut and oral microbiome and pancreatic cancer. However, the intricacies of this association within the Japanese population remain unclear. In this study, we investigated the gut and oral microbiomes of Japanese patients with pancreatic cancer, comparing them with those of healthy individuals.<br><br>METHODS: We recruited 30 patients with untreated pancreatic cancer and 18 healthy controls at Kyoto University Hospital (2018-2022). We performed a comprehensive 16S rRNA gene sequencing to analyze their gut and oral microbiomes.<br><br>RESULTS: Analysis revealed that the diversity of the gut and oral microbiomes of patients with pancreatic cancer was reduced compared to that of the healthy controls. Specifically, we observed an increase in the genus Streptococcus in both the gut and oral microbiomes and a significant decrease in several butyrate-producing bacteria in fecal samples. Moreover, bacteria such as Streptococcus mitis and Holdemanella biformis were present in pancreatic cancer tissues, suggesting that they might influence the carcinogenesis and progression of pancreatic cancer.<br><br>CONCLUSIONS: The gut and oral microbiome differed between patients with pancreatic cancer and healthy controls, with a notable decrease in butyrate-producing bacteria in the gut microbiome of the patients. This suggests that there may be a distinct microbial signature associated with pancreatic cancer in the Japanese population. Further studies are required to elucidate the microbiome's causal role in this cancer and help develop prognostic markers or targeted therapies.}, }
@article {pmid39253878, year = {2024}, author = {Jangi, S and Hecht, G}, title = {Microbiome 2.0: lessons from the 2024 Gut Microbiota for Health World Summit.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2400579}, pmid = {39253878}, issn = {1949-0984}, support = {K12 TR004384/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Probiotics/administration &amp; dosage ; }, abstract = {This Meeting Summary highlights the key insights from the 12th meeting of the Gut Microbiota for Health World Summit, held in Washington, DC, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM). Through a 2-day series of plenary sessions, workshops, a poster session, and live discussions involving thought leaders, physicians, researchers, and representatives from the Food and Drug Administration and the pharmaceutical industry, the conference attendees focused on the strategies and challenges in developing microbiome-based therapies to prevent and treat human disease. The conference highlighted progress in the field, including the recently successful introduction of 2 new fecal microbial transplantation-based products into the clinical setting, and the continuing development of next-generation probiotics. However, to continue to advance microbiome-directed treatments, three key themes emerged during the meeting, including (1) better methods to identify actionable targets in the microbiome (2) developing effective strategies to manipulate the microbiome (3) aligning microbiome-based therapies with existing treatment paradigms in the real world.}, }
@article {pmid39252488, year = {2024}, author = {Park, J and Hong, SN and Lee, HS and Shin, J and Oh, EH and Nam, K and Seong, G and Kim, HG and Kim, JO and Jeon, SR and , }, title = {Perception of fecal microbiota transplantation in patients with ulcerative colitis in Korea: a KASID multicenter study.}, journal = {The Korean journal of internal medicine}, volume = {39}, number = {5}, pages = {783-792}, pmid = {39252488}, issn = {2005-6648}, support = {//Soonchunhyang University/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy/microbiology/diagnosis ; Male ; Female ; Adult ; Republic of Korea ; Middle Aged ; Prospective Studies ; *Health Knowledge, Attitudes, Practice ; Patient Education as Topic ; Patient Preference ; Treatment Outcome ; Patient Acceptance of Health Care ; Young Adult ; Aged ; Perception ; }, abstract = {BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) is a promising therapy for inducing and maintaining remission in patients with ulcerative colitis (UC). However, FMT has not been approved for UC treatment in Korea. Our study aimed to investigate patient perceptions of FMT under the national medical policy.<br><br>METHODS: This was a prospective, multicenter study. Patients with UC &#x2265; 19 years of age were included. Patients were surveyed using 22 questions on FMT. Changes in perceptions of FMT before and after education were also compared.<br><br>RESULTS: A total of 210 patients with UC were enrolled. We found that 51.4% of the patients were unaware that FMT was an alternative treatment option for UC. After reading the educational materials on FMT, more patients were willing to undergo this procedure (27.1% vs. 46.7%; p < 0.001). The preferred fecal donor was the one recommended by a physician (41.0%), and the preferred transplantation method was the oral capsule (30.4%). A large proportion of patients (50.0%) reported that the national medical policy influenced their choice of FMT treatment. When patients felt severe disease activity, their willingness to undergo FMT increased (92.3% vs. 43.1%; p = 0.001).<br><br>CONCLUSION: Education can increase preference for FMT in patients with UC. When patients have severe disease symptoms or their quality of life decreases their willingness to undergo FMT increases. Moreover, national medical policies may influence patient choices regarding FMT.}, }
@article {pmid39252487, year = {2024}, author = {Kim, YC and Sohn, KH and Kang, HR}, title = {Gut microbiota dysbiosis and its impact on asthma and other lung diseases: potential therapeutic approaches.}, journal = {The Korean journal of internal medicine}, volume = {39}, number = {5}, pages = {746-758}, pmid = {39252487}, issn = {2005-6648}, support = {RS-2023-00217157//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; }, mesh = {Humans ; *Dysbiosis ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Asthma/microbiology/immunology/therapy ; *Fecal Microbiota Transplantation ; *Prebiotics ; Animals ; Lung/microbiology/immunology/metabolism ; Lung Diseases/microbiology/therapy/immunology ; }, abstract = {The emerging field of gut-lung axis research has revealed a complex interplay between the gut microbiota and respiratory health, particularly in asthma. This review comprehensively explored the intricate relationship between these two systems, focusing on their influence on immune responses, inflammation, and the pathogenesis of respiratory diseases. Recent studies have demonstrated that gut microbiota dysbiosis can contribute to asthma onset and exacerbation, prompting investigations into therapeutic strategies to correct this imbalance. Probiotics and prebiotics, known for their ability to modulate gut microbial compositions, were discussed as potential interventions to restore immune homeostasis. The impact of antibiotics and metabolites, including short-chain fatty acids produced by the gut microbiota, on immune regulation was examined. Fecal microbiota transplantation has shown promise in various diseases, but its role in respiratory disorders is not established. Innovative approaches, including mucus transplants, inhaled probiotics, and microencapsulation strategies, have been proposed as novel therapeutic avenues. Despite challenges, including the sophisticated adaptability of microbial communities and the need for mechanistic clarity, the potential for microbiota-based interventions is considerable. Collaboration between researchers, clinicians, and other experts is essential to unravel the complexities of the gut-lung axis, paving a way for innovative strategies that could transform the management of respiratory diseases.}, }
@article {pmid39252485, year = {2024}, author = {Seo, J and Choi, CH}, title = {Seeking acceptance: how education shifts views on fecal microbiota transplants for ulcerative colitis in Korea.}, journal = {The Korean journal of internal medicine}, volume = {39}, number = {5}, pages = {697-699}, pmid = {39252485}, issn = {2005-6648}, }
@article {pmid39251400, year = {2025}, author = {Patel, SK and Gooya, M and Guo, Q and Noel, S and Rabb, H}, title = {The microbiome and acute organ injury: focus on kidneys.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {40}, number = {3}, pages = {423-434}, pmid = {39251400}, issn = {1460-2385}, support = {R01 DK123342/DK/NIDDK NIH HHS/United States ; R01 DK132278/DK/NIDDK NIH HHS/United States ; R01DK123342/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Acute Kidney Injury/microbiology/etiology ; *Microbiota ; Animals ; Critical Illness ; }, abstract = {The microbiome of critically ill patients is significantly altered by both effects of the illnesses and clinical interventions provided during intensive care. Studies have shown that manipulating the microbiome can prevent or modulate complications of critical illness in experimental models and preliminary clinical trials. This review aims to discuss general concepts about the microbiome, including mechanisms of modifying acute organ dysfunction. The focus will be on the effects of microbiome modulation during experimental acute kidney injury (excluding septic acute kidney injury) and comparison with other experimental acute organ injuries commonly seen in critically ill patients.}, }
@article {pmid39249130, year = {2024}, author = {Ju, T and Song, Z and Qin, D and Cheng, J and Li, T and Hu, G and Fu, S}, title = {Neohesperidin Attenuates DSS-Induced Ulcerative Colitis by Inhibiting Inflammation, Reducing Intestinal Barrier Damage, and Modulating Intestinal Flora Composition.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {37}, pages = {20419-20431}, doi = {10.1021/acs.jafc.4c04433}, pmid = {39249130}, issn = {1520-5118}, mesh = {*Colitis, Ulcerative/drug therapy/chemically induced/microbiology/immunology ; Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Dextran Sulfate/adverse effects ; Male ; *Mice, Inbred C57BL ; *Intestinal Mucosa/metabolism/drug effects/microbiology ; *Hesperidin/pharmacology/administration &amp; dosage/analogs &amp; derivatives ; Humans ; Bacteria/classification/drug effects/isolation &amp; purification/genetics ; NF-kappa B/metabolism/genetics ; Colon/microbiology/drug effects/immunology/metabolism/pathology ; Disease Models, Animal ; Inflammation/drug therapy ; }, abstract = {Flavonoid natural products are emerging as a promising approach for treating Ulcerative Colitis (UC) due to their natural origin and minimal toxicity. This study investigates the effects of Neohesperidin (NEO), a natural flavonoid, on Dextran Sodium Sulfate (DSS)-induced UC in mice, focusing on the underlying molecular mechanisms. Early intervention with NEO (25 and 50 mg/kg) mitigated colon shortening, restored damaged barrier proteins, and significantly reduced the inflammatory cytokine levels. Moreover, NEO inhibited the MAPK/NF-κB signaling pathway and enhanced the levels of intestinal barrier proteins (Claudin-3 and ZO-1). Additionally, NEO increased beneficial intestinal probiotics (S24-7 and Lactobacillaceae) while reducing harmful bacteria (Erysipelotrichi, Enterobacteriaceae). Fecal microbial transplantation (FMT) results demonstrated that NEO (50 mg/kg) markedly improved UC symptoms. In conclusion, early NEO intervention may alleviate DSS-induced UC by inhibiting inflammatory responses, preserving intestinal barrier integrity and modulating gut microbiota.}, }
@article {pmid39247802, year = {2024}, author = {Naji, A and Siskin, D and Woodworth, MH and Lee, JR and Kraft, CS and Mehta, N}, title = {The Role of the Gut, Urine, and Vaginal Microbiomes in the Pathogenesis of Urinary Tract Infection in Women and Consideration of Microbiome Therapeutics.}, journal = {Open forum infectious diseases}, volume = {11}, number = {9}, pages = {ofae471}, pmid = {39247802}, issn = {2328-8957}, abstract = {The gut, urine, and vaginal microbiomes play significant roles in the pathogenesis of recurrent urinary tract infections (rUTIs). Analysis of these microbiota has shown distinct associations with urinary tract infections. Encouraging data indicate that rUTIs may be responsive to microbiome treatments such as fecal microbiota transplantation, expanding potential treatments beyond antibiotics, hydration, and behavioral interventions. If successful, these nonantibiotic therapies have the potential to increase time between rUTI episodes and reduce the prevalence of multidrug-resistant organisms. In this review, we discuss the role of the 3 microbiomes in the pathogenesis of rUTI and utilization of live biotherapeutic products as therapy for rUTI.}, }
@article {pmid39247190, year = {2024}, author = {Strzępa, A and Marcińska, K and Kiecka, A and Majewska-Szczepanik, M and Szczepanik, M}, title = {Proton pump inhibitor alters Th17/Treg balance and induces gut dysbiosis suppressing contact hypersensitivity reaction in mice.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1390025}, pmid = {39247190}, issn = {1664-3224}, mesh = {Animals ; *Proton Pump Inhibitors/adverse effects/pharmacology ; *Gastrointestinal Microbiome/drug effects/immunology ; *Th17 Cells/immunology/metabolism ; Mice ; *T-Lymphocytes, Regulatory/immunology ; *Dysbiosis ; *Omeprazole/pharmacology ; Disease Models, Animal ; Cytokines/metabolism ; Female ; Mice, Inbred C57BL ; Dermatitis, Contact/immunology/etiology ; }, abstract = {Proton pump inhibitors (PPIs), such as omeprazole, are the most commonly prescribed drugs. Treatment with PPIs alters gut microbiota composition and reduces the production of reactive oxygen (ROS) and proinflammatory IL-1β, IL-6, and TNF-α cytokines. Here, using the T cell-dependent contact hypersensitivity (CHS) response, an animal model of allergic contact dermatitis (ACD) that affects up to 30% of the population, we demonstrated that a two-week omeprazole treatment suppresses the development of CHS. Omeprazole treatment before CHS induction, reduced inflammatory response in ears measured by ear swelling, ear biopsy weight, MPO activity, and proinflammatory cytokine production. These changes were associated with reduced frequency of TCRαβ[+] CD4[+] IL-17A[+] and TCRαβ[+] CD8[+] IL-17A[+] T cells and increased frequency of TCRαβ[+] CD4[+] CD25[+] FoxP3[+] Treg, and TCRαβ[+] CD4+ IL-10+ Tr1 cells in peripheral lymphoid organs. Omeprazole treatment decreased the production of ROS, TNF-α, and IL-6, which supported Th17 cell induction, and increased the frequency of Clostridium cluster XIVab and Lactobacillus, implicated in Treg cell induction. The fecal microbiota transplantation (FMT) experiment confirmed the role of omeprazole-induced changes in gut microbiota profile in CHS suppression. Our data suggests that omeprazole ameliorates inflammatory response mediated by T-cells.}, }
@article {pmid39245800, year = {2024}, author = {Ge, P and Xie, H and Guo, Y and Jin, H and Chen, L and Chen, Z and Liu, Y}, title = {Linoleyl acetate and mandenol alleviate HUA-induced ED via NLRP3 inflammasome and JAK2/STAT3 signalling conduction in rats.}, journal = {Journal of cellular and molecular medicine}, volume = {28}, number = {17}, pages = {e70075}, pmid = {39245800}, issn = {1582-4934}, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Janus Kinase 2/metabolism ; Male ; *Inflammasomes/metabolism ; *STAT3 Transcription Factor/metabolism ; *Signal Transduction/drug effects ; Rats ; *Rats, Sprague-Dawley ; *Erectile Dysfunction/drug therapy/etiology/metabolism ; *Hyperuricemia/drug therapy/complications ; Apoptosis/drug effects ; Disease Models, Animal ; }, abstract = {Hyperuricemia (HUA) is characterized by elevated blood uric acid levels, which can increase the risk of erectile dysfunction (ED). Clinical studies have demonstrated satisfactory efficacy of a traditional Chinese medicine formula QYHT decoction in improving ED. Furthermore, the main monomeric components of this formula, linoleyl acetate and mandenol, demonstrate promise in the treatment of ED. This study established an ED rat model induced by HUA and the animals were administered with linoleyl acetate and mandenol. HE and TUNEL were performed to detect tissue changes, ELISA to measure the levels of serum testosterone (T), MDA, NO, CRP, and TNF-α and qPCR and WB to assess the expression levels of NLRP3, ASC, Caspase-1, JAK2, and STAT3 in whole blood. The findings showed that linoleyl acetate and mandenol improved kidney tissue morphology, reduced cell apoptosis in penile tissue, significantly increased T and NO levels, while substantially decreasing levels of MDA, CRP, and TNF-α. Meanwhile, the expression of NLRP3, ASC, and Caspase-1 mRNAs and proteins was markedly reduced, and the phosphorylation of JAK2 and STAT3 was inhibited. These findings were further validated through faecal microbiota transplantation results. Taken together, linoleyl acetate and mandenol could inhibit NLRP3 inflammasome activation, reduce inflammatory and oxidative stress responses, suppress the activity of JAK-STAT signalling pathway, ultimately providing a potential treatment for HUA-induced ED.}, }
@article {pmid39245217, year = {2024}, author = {Banerjee, A and Chatterji, U}, title = {Prevalence of perturbed gut microbiota in pathophysiology of arsenic-induced anxiety- and depression-like behaviour in mice.}, journal = {Chemosphere}, volume = {364}, number = {}, pages = {143293}, doi = {10.1016/j.chemosphere.2024.143293}, pmid = {39245217}, issn = {1879-1298}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Arsenic/toxicity ; *Anxiety/chemically induced ; Mice ; *Depression/chemically induced ; Male ; Brain/drug effects ; Brain-Gut Axis/physiology/drug effects ; Behavior, Animal/drug effects ; Dysbiosis/chemically induced ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Lipopolysaccharides ; }, abstract = {Severe toxic effects of arsenic on human physiology have been of immense concern worldwide. Arsenic causes irrevocable structural and functional disruption of tissues, leading to major diseases in chronically exposed individuals. However, it is yet to be resolved whether the effects result from direct deposition and persistence of arsenic in tissues, or via activation of indirect signaling components. Emerging evidences suggest that gut inhabitants play an active role in orchestrating various aspects of brain physiology, as the gut-brain axis maintains cognitive health, emotions, learning and memory skills. Arsenic-induced dysbiosis may consequentially evoke neurotoxicity, eventually leading to anxiety and depression. To delineate the mechanism of action, mice were exposed to different concentrations of arsenic. Enrichment of Gram-negative bacteria and compromised barrier integrity of the gut enhanced lipopolysaccharide (LPS) level in the bloodstream, which in turn elicited systemic inflammation. Subsequent alterations in neurotransmitter levels, microglial activation and histoarchitectural disruption in brain triggered onset of anxiety- and depression-like behaviour in a dose-dependent manner. Finally, to confirm whether the neurotoxic effects are specifically a consequence of modulation of gut microbiota (GM) by arsenic and not arsenic accumulation in the brain, fecal microbiota transplantations (FMT) were performed from arsenic-exposed mice to healthy recipients. 16S rRNA gene sequencing indicated major alterations in GM population in FMT mice, leading to severe structural, functional and behavioural alterations. Moreover, suppression of Toll-like receptor 4 (TLR4) using vivo-morpholino oligomers (VMO) indicated restoration of the altered parameters towards normalcy in FMT mice, confirming direct involvement of the GM in inducing neurotoxicity through the arsenic-gut-brain axis. This study accentuates the potential role of the gut microbiota in promoting neurotoxicity in arsenic-exposed mice, and has immense relevance in predicting neurotoxicity under altered conditions of the gut for designing therapeutic interventions that will target gut dysbiosis to attenuate arsenic-mediated neurotoxicity.}, }
@article {pmid39240145, year = {2025}, author = {Moutsoglou, D and Syal, A and Lopez, S and Nelson, EC and Chen, L and Kabage, AJ and Fischer, M and Khoruts, A and Vaughn, BP and Staley, C}, title = {Novel Microbial Engraftment Trajectories Following Microbiota Transplant Therapy in Ulcerative Colitis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {19}, number = {2}, pages = {}, doi = {10.1093/ecco-jcc/jjae142}, pmid = {39240145}, issn = {1876-4479}, support = {T32 HL144472/HL/NHLBI NIH HHS/United States ; //Pfizer's Investigator Sponsored Research Support/ ; }, mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Adult ; *Gastrointestinal Microbiome ; Middle Aged ; Bayes Theorem ; Feces/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Microbiota transplant therapy (MTT) is an emerging treatment for ulcerative colitis (UC). One proposed mechanism for the benefit of MTT is through engraftment of donor microbiota; however, engraftment kinetics are unknown. We identified SourceTracker as an efficient method both to determine engraftment and for the kinetic study of engrafting donor taxa to aid in determining the mechanism of how this therapy may treat UC.<br><br>METHODS: Ulcerative colitis patients received either encapsulated (drug name MTP-101C) or placebo capsules daily for 8 weeks followed by a 4-week washout period. Amplicon sequence data from donors and patients were analyzed using the Bayesian algorithm SourceTracker.<br><br>RESULTS: Twenty-seven patients were enrolled, 14 to placebo and 13 to MTT. Baseline Shannon and Chao1 indices negatively correlated with week 12 donor engraftment for patients treated with active drug capsules but not for placebo patients. SourceTracker engraftment positively correlated with the week 12 distance from donors measured using the Bray-Curtis similarity metric in treated patients but not with placebo. Engraftment at week 12 was significantly higher in the MTT group than in the placebo group. We identified engrafting taxa from donors in our patients and quantified the proportion of donor similarity or engraftment during weeks 1 through 8 (active treatment) and week 12, 4 weeks after the last dose.<br><br>CONCLUSION: SourceTracker can be used as a simple and reliable method to quantify donor microbial community engraftment and donor taxa contribution in patients with UC and other inflammatory conditions treated with MTT.}, }
@article {pmid39239516, year = {2024}, author = {Wang, M and Sun, P and Chai, X and Liu, YX and Li, L and Zheng, W and Chen, S and Zhu, X and Zhao, S}, title = {Reconstituting gut microbiota-colonocyte interactions reverses diet-induced cognitive deficits: The beneficial of eucommiae cortex polysaccharides.}, journal = {Theranostics}, volume = {14}, number = {12}, pages = {4622-4642}, pmid = {39239516}, issn = {1838-7640}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Diet, High-Fat/adverse effects ; Mice ; *Cognitive Dysfunction/therapy ; *Polysaccharides/pharmacology ; *Fecal Microbiota Transplantation ; *Mice, Inbred C57BL ; Male ; *Dysbiosis/therapy ; Colon/microbiology ; Escherichia coli ; Butyrates/metabolism ; Proteobacteria/isolation &amp; purification/drug effects ; Disease Models, Animal ; }, abstract = {Rationale: Consumption of a high-fat diet (HFD) has been implicated in cognitive deficits and gastrointestinal dysfunction in humans, with the gut microbiota emerging as a pivotal mediator of these diet-associated pathologies. The introduction of plant-based polysaccharides into the diet as a therapeutic strategy to alleviate such conditions is gaining attention. Nevertheless, the mechanistic paradigm by which polysaccharides modulate the gut microbiota remains largely undefined. This study investigated the mechanisms of action of Eucommiae cortex polysaccharides (EPs) in mitigating gut dysbiosis and examined their contribution to rectifying diet-related cognitive decline. Methods: Initially, we employed fecal microbiota transplantation (FMT) and gut microbiota depletion to verify the causative role of changes in the gut microbiota induced by HFD in synapse engulfment-dependent cognitive impairments. Subsequently, colonization of the gut of chow-fed mice with Escherichia coli (E. coli) from HFD mice confirmed that inhibition of Proteobacteria by EPs was a necessary prerequisite for alleviating HFD-induced cognitive impairments. Finally, supplementation of HFD mice with butyrate and treatment of EPs mice with GW9662 demonstrated that EPs inhibited the expansion of Proteobacteria in the colon of HFD mice by reshaping the interactions between the gut microbiota and colonocytes. Results: Findings from FMT and antibiotic treatments demonstrated that HFD-induced cognitive impairments pertaining to neuronal spine loss were contingent on gut microbial composition. Association analysis revealed strong associations between bacterial taxa belonging to the phylum Proteobacteria and cognitive performance in mice. Further, introducing E. coli from HFD-fed mice into standard diet-fed mice underscored the integral role of Proteobacteria proliferation in triggering excessive synaptic engulfment-related cognitive deficits in HFD mice. Crucially, EPs effectively counteracted the bloom of Proteobacteria and subsequent neuroinflammatory responses mediated by microglia, essential for cognitive improvement in HFD-fed mice. Mechanistic insights revealed that EPs promoted the production of bacteria-derived butyrate, thereby ameliorating HFD-induced colonic mitochondrial dysfunction and reshaping colonocyte metabolism. This adjustment curtailed the availability of growth substrates for facultative anaerobes, which in turn limited the uncontrolled expansion of Proteobacteria. Conclusions: Our study elucidates that colonocyte metabolic disturbances, which promote Proteobacteria overgrowth, are a likely cause of HFD-induced cognitive deficits. Furthermore, dietary supplementation with EPs can rectify behavioral dysfunctions associated with HFD by modifying gut microbiota-colonocyte interactions. These insights contribute to the broader understanding of the modulatory effects of plant prebiotics on the microbiota-gut-brain axis and suggest a potential therapeutic avenue for diet-associated cognitive dysfunction.}, }
@article {pmid39238062, year = {2024}, author = {Lv, Y and Ge, C and Wu, L and Hu, Z and Luo, X and Huang, W and Zhan, S and Shen, X and Yu, D and Liu, B}, title = {Hepatoprotective effects of magnolol in fatty liver hemorrhagic syndrome hens through shaping gut microbiota and tryptophan metabolic profile.}, journal = {Journal of animal science and biotechnology}, volume = {15}, number = {1}, pages = {120}, pmid = {39238062}, issn = {1674-9782}, abstract = {BACKGROUND: Magnolol (MAG) exhibits hepatoprotective activity, however, whether and how MAG regulates the gut microbiota to alleviate fatty liver hemorrhagic syndrome (FLHS) remains unclear. Therefore, we investigated the mechanism of MAG in FLHS laying hens with an emphasis on alterations in the gut-liver axis. We randomly divided 540 56-week-old Hy-line white laying hens with FLSH into 4 groups. The birds were fed a high-fat low-protein (HFLP) diet (CON) or HELP diets supplemented with 200, 400, and 600 mg/kg of MAG (M1, M2, and M3, respectively) for 9 weeks.<br><br>RESULTS: Magnolol supplementation increased the laying rate and ameliorated hepatic damage and dysfunction by regulating lipid metabolism, improving intestinal barrier function, and shaping the gut microbiota and tryptophan metabolic profiles. Dietary MAG supplementation downregulated the expression of lipid synthesis genes and upregulated the expression of lipid transport genes at varying degrees. The intestinal barrier function was improved by 200 and 400 mg/kg of MAG supplementation, as evidenced by the increased villus height and mRNA expression of tight junction related genes. Microbiological profile information revealed that MAG changed the gut microbiota, especially by elevating the abundances of Lactobacillus, Faecalibacterium, and Butyricicoccus. Moreover, non-targeted metabolomic analysis showed that MAG significantly promoted tryptophan metabolites, which was positively correlated with the MAG-enriched gut microbiota. The increased tryptophan metabolites could activate aryl hydrocarbon receptor (AhR) and relieved hepatic inflammation and immune response evidenced by the downregulated the gene expression levels of pro-inflammatory cytokines such as interleukin-1&#x3b2; (IL-1&#x3b2;), tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), and interleukin-6 (IL-6) in the liver. The fecal microbiota transplantation (FMT) experiments further confirmed that the hepatoprotective effect is likely mediated by MAG-altered gut microbiota and their metabolites.<br><br>CONCLUSIONS: Magnolol can be an outstanding supplement for the prevention and mitigation of FLHS in laying hens by positively regulating lipid synthesis and transport metabolism, improving the intestinal barrier function, and relieving hepatic inflammation by reshaping the gut microbiota and metabolite profiles through gut microbiota-indole metabolite-hepatic AhR crosstalk. These findings elucidate the mechanisms by which MAG alleviates FLHS and provide a promising method for preventing liver diseases by modulating gut microbiota and their metabolites.}, }
@article {pmid39235561, year = {2025}, author = {Jiang, SS and Kang, ZR and Chen, YX and Fang, JY}, title = {The gut microbiome modulate response to immunotherapy in cancer.}, journal = {Science China. Life sciences}, volume = {68}, number = {2}, pages = {381-396}, pmid = {39235561}, issn = {1869-1889}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology/microbiology ; Tumor Microenvironment/immunology ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors. Currently, clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of cancers. Preclinical investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer immunotherapy. Certain microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune cells. Understanding how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment strategies. Fecal microbial transplants, probiotics, dietary interventions, and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the immunotherapy. Ongoing clinical trials are evaluating these approaches. This review presents the recent advancements in understanding the dynamic interplay among the host immunity, the microbiome, and cancer immunotherapy, as well as strategies for modulating the microbiome, with a view to translating into clinical applications.}, }
@article {pmid39235366, year = {2024}, author = {Liu, L and Ma, L and Liu, H and Zhao, F and Li, P and Zhang, J and Lü, X and Zhao, X and Yi, Y}, title = {Targeted discovery of gut microbiome-remodeling compounds for the treatment of systemic inflammatory response syndrome.}, journal = {mSystems}, volume = {9}, number = {10}, pages = {e0078824}, pmid = {39235366}, issn = {2379-5077}, support = {82141201,32272297//National Natural Science Foundation of China (NSFC)/ ; 2023-YBNY-157//Key Research and Development Projects of Shaanxi Province/ ; CBCM2020204//Foundation of State Key Laboratory of Component-Based Chinese Medicine/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; *Systemic Inflammatory Response Syndrome/drug therapy ; Animals ; Mice ; Humans ; *Fecal Microbiota Transplantation ; Male ; Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Female ; }, abstract = {Systemic inflammatory response syndrome (SIRS) is a severe inflammatory response that can lead to organ dysfunction and death. Modulating the gut microbiome is a promising therapeutic approach for managing SIRS. This study assesses the therapeutic potential of the Xuanfei Baidu (XFBD) formula in treating SIRS. The results showed that XFBD administration effectively reduced mortality rates and inflammation in SIRS mice. Using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we substantiated that the therapeutic effects of XFBD are partly attributed to gut microbiota modulation. We conducted in vitro experiments to accurately assess the gut microbiome remodeling effects of 51 compounds isolated from XFBD. These compounds exhibited varying abilities to induce a microbial structure that closely resembles that of the healthy control group. By quantifying their impact on microbial structure and clustering their regulatory patterns, we devised multiple gut microbiome remodeling compound (GMRC) cocktails. GMRC cocktail C, comprising aucubin, gentiopicroside, syringic acid, gallic acid, p-hydroxybenzaldehyde, para-hydroxybenzoic acid, and isoimperatorin, demonstrated superior efficacy in treating SIRS compared to a single compound or to other cocktails. Finally, in vitro experiments showcased that GMRC cocktail C effectively rebalanced bacteria composition in SIRS patients. This study underscores XFBD's therapeutic potential in SIRS and highlights the importance of innovative treatment approaches for this disease by targeting the gut microbiota.IMPORTANCEDeveloping effective treatment strategies for systemic inflammatory response syndrome (SIRS) is crucial due to its severe and often life-threatening nature. While traditional treatments like dexamethasone have shown efficacy, they also come with significant side effects and limitations. This study makes significant strides by demonstrating that the Xuanfei Baidu (XFBD) formula can substantially reduce mortality rates and inflammation in SIRS mice through effective modulation of the gut microbiota. By quantitatively assessing the impact of 51 compounds derived from XFBD on the gut microbiome, we developed a potent gut microbiome remodeling compound cocktail. This cocktail outperformed individual compounds and other mixtures in efficacy against SIRS. These findings highlight the potential of XFBD as a therapeutic solution for SIRS and underscore the critical role of innovative strategies targeting the gut microbiota in addressing this severe inflammatory condition.}, }
@article {pmid39234553, year = {2024}, author = {Xu, J and Zou, Z and Li, X and Sun, X and Wang, X and Qin, F and Abulizi, A and Chen, Q and Pan, Z and Shen, H and Lv, Y and Yan, R}, title = {Effect of Gegen Qinlian Decoction on the regulation of gut microbiota and metabolites in type II diabetic rats.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1429360}, pmid = {39234553}, issn = {1664-302X}, abstract = {Gegen Qinlian Decoction (GGQLT) is a traditional Chinese herbal medicine that has been reported to have a significant therapeutic effect in the management of type II diabetes mellitus (T2DM). In this study, we constructed a T2DM rat model by feeding a high-fat diet and injecting streptozotocin (STZ) and tested the effects of feeding GGQLT and fecal transplantation on the physiological indices, microbiota, and metabolism of rats. The results showed that the administration of GGQLT can significantly improve the growth performance of rats and has a remarkable antihyperlipidemic effect. In addition, GGQLT altered the composition of gut microbiota by increasing beneficial bacteria such as Coprococcus, Bifidobacterium, Blautia, and Akkermansia. In addition, GGQLT elevated levels of specific bile acids by metabolomic analysis, potentially contributing to improvements in lipid metabolism. These findings suggest that GGQLT may have beneficial effects on T2DM by influencing lipid metabolism and gut microbiota. However, further studies are needed to elucidate its mechanisms and assess clinical applications.}, }
@article {pmid39230353, year = {2025}, author = {Bland, CM and Love, BL and Jones, BM}, title = {Human microbiome: Impact of newly approved treatments on C. difficile infection.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {82}, number = {4}, pages = {174-183}, doi = {10.1093/ajhp/zxae249}, pmid = {39230353}, issn = {1535-2900}, mesh = {Humans ; *Clostridium Infections/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Clostridioides difficile ; *Microbiota/physiology ; *Gastrointestinal Microbiome/physiology/drug effects ; Drug Approval ; }, abstract = {PURPOSE: The primary purposes of this review are to provide a brief overview of the microbiome, discuss the most relevant outcome data and key characteristics of each live microbiome agent, and pose questions for consideration going forward as these agents are integrated into clinical practice.<br><br>SUMMARY: The management of Clostridiodes difficile infection (CDI) remains a difficult clinical conundrum, with recurrent CDI occurring in 15% to 35% of patients and causing significant morbidity and decreased quality of life. For patients with frequent CDI recurrences, fecal microbiota transplantation (FMT) has been demonstrated to have significant benefit but also significant risks, and FMT is not approved by the US Food and Drug Administration (FDA) for that indication. FDA has established a new therapeutic class for agents known as live biotherapeutic products (LBPs) that offer significant advantages over FMT, including standardized screening, testing, and manufacturing as well as known quantities of organisms contained within. Two new live microbiome products within this class were recently approved by FDA for prevention of CDI recurrences in adult patients following treatment for recurrent CDI with standard antimicrobial therapy. Both agents had demonstrated efficacy in registry trials in preventing CDI recurrence but differ significantly in a number of characteristics, such as route of administration. Cost as well as logistics are current obstacles to use of these therapies.<br><br>CONCLUSION: Live microbiome therapy is a promising solution for patients with recurrent CDI. Future studies should provide further evidence within yet-to-be-evaluated populations not included in registry studies. This along with real-world evidence will inform future use and clinical guideline placement.}, }
@article {pmid39230037, year = {2025}, author = {Vaughn, BP and Khoruts, A and Fischer, M}, title = {Diagnosis and Management of Clostridioides difficile in Inflammatory Bowel Disease.}, journal = {The American journal of gastroenterology}, volume = {120}, number = {2}, pages = {313-319}, doi = {10.14309/ajg.0000000000003076}, pmid = {39230037}, issn = {1572-0241}, mesh = {Humans ; *Inflammatory Bowel Diseases/complications/microbiology ; *Clostridium Infections/diagnosis/drug therapy/therapy/complications ; *Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/isolation &amp; purification ; Gastrointestinal Microbiome ; Broadly Neutralizing Antibodies/therapeutic use ; Fecal Microbiota Transplantation ; Risk Factors ; Antibodies, Monoclonal ; }, abstract = {Patients with inflammatory bowel disease (IBD) have an increased risk of Clostridioides difficile infection (CDI), which can lead to worse IBD outcomes. The diagnosis of CDI in patients with IBD is complicated by higher C. difficile colonization rates and shared clinical symptoms of intestinal inflammation. Traditional risk factors for CDI, such as antibiotic exposure, may be lacking in patients with IBD because of underlying intestinal microbiota dysbiosis. Although CDI disproportionately affects people with IBD, patients with IBD are typically excluded from CDI clinical trials creating a knowledge gap in the diagnosis and management of these 2 diseases. This narrative review aims to provide a comprehensive overview of the diagnosis, treatment, and prevention of CDI in patients with IBD. Distinguishing CDI from C. difficile colonization in the setting of an IBD exacerbation is important to avoid treatment delays. When CDI is diagnosed, extended courses of anti- C. difficile antibiotics may lead to better CDI outcomes. Regardless of a diagnosis of CDI, the presence of C. difficile in a patient with IBD should prompt a disease assessment of the underlying IBD. Microbiota-based therapies and bezlotoxumab seem to be effective in preventing CDI recurrence in patients with IBD. Patients with IBD should be considered at high risk of CDI recurrence and evaluated for a preventative strategy when diagnosed with CDI. Ultimately, the comanagement of CDI in a patient with IBD requires a nuanced, patient-specific approach to distinguish CDI from C. difficile colonization, prevent CDI recurrence, and manage the underlying IBD.}, }
@article {pmid39226363, year = {2024}, author = {Zhang, N and Zhang, R and Jiang, L and Gao, Z and Xia, W and Ma, X and Qin, Y and Zhang, D and Li, J and Tian, P and Zhang, Q and Wang, W and Zhang, K and Xu, S and Zhao, N and Xu, S}, title = {Inhibition of colorectal cancer in Alzheimer's disease is mediated by gut microbiota via induction of inflammatory tolerance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {37}, pages = {e2314337121}, pmid = {39226363}, issn = {1091-6490}, support = {82100863//MOST | National Natural Science Foundation of China (NSFC)/ ; H2020206105//Hebei Natural Science Foundation/ ; H2018206358//Hebei Natural Science Foundation/ ; C20210346//Funding project for introducing overseas students of Hebei Province/ ; 20211628//Medical Science Research Project of Hebei Province/ ; ZF2023029//Hebei Province Government-funded Excellent Talents Project in Clinical Medicine/ ; 20377707D//The Science and Technology project of the People's Livelihood in Hebei Province/ ; 206Z7701G//Special Funding for Local Science and Technology Development Guided by the Central Government/ ; 2019-I2M-5-055//CAMS Innovation Fund for Medical Sciences/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Alzheimer Disease/microbiology ; *Colorectal Neoplasms/microbiology/immunology/pathology ; Mice ; Humans ; *Fecal Microbiota Transplantation ; Male ; Inflammation ; Cognitive Dysfunction ; Female ; Prevotella ; Disease Models, Animal ; Lipopolysaccharides ; Carcinogenesis ; Dextran Sulfate ; }, abstract = {Epidemiological studies have revealed an inverse relationship between the incidence of Alzheimer's disease (AD) and various cancers, including colorectal cancer (CRC). We aimed to determine whether the incidence of CRC is reduced in AD-like mice and whether gut microbiota confers resistance to tumorigenesis through inducing inflammatory tolerance using 16S ribosomal RNA gene sequencing and fecal microbiota transplantation (FMT). AD-like mice experienced a significantly decreased incidence of CRC tumorigenesis induced by azoxymethane-dextran sodium sulfate as evidenced by suppressed intestinal inflammation compared with control mice. However, FMT from age-matched control mice reversed the inhibitory effects on the tumorigenesis of CRC and inflammatory response in AD-like mice. The key bacterial genera in gut microbiota, including Prevotella, were increased in both the AD-like mice and in patients with amnestic mild cognitive impairment (aMCI) but were decreased in patients with CRC. Pretreatment with low-dose Prevotella-derived lipopolysaccharides (LPS) induced inflammatory tolerance both in vivo and in vitro and inhibited CRC tumorigenesis in mice. Imbalanced gut microbiota increased intestinal barrier permeability, which facilitated LPS absorption from the gut into the blood, causing cognitive decline in AD-like mice and patients with aMCI. These data reveal that intestinal Prevotella-derived LPS exerts a resistant effect to CRC tumorigenesis via inducing inflammatory tolerance in the presence of AD. These findings provide biological evidence demonstrating the inverse relationship between the incidence of AD and CRC.}, }
@article {pmid39226184, year = {2024}, author = {Zhai, Z and Yang, Y and Chen, S and Wu, Z}, title = {Long-Term Exposure to Polystyrene Microspheres and High-Fat Diet-Induced Obesity in Mice: Evaluating a Role for Microbiota Dysbiosis.}, journal = {Environmental health perspectives}, volume = {132}, number = {9}, pages = {97002}, pmid = {39226184}, issn = {1552-9924}, mesh = {Animals ; *Dysbiosis/microbiology ; Mice ; *Obesity/microbiology ; *Diet, High-Fat ; *Mice, Inbred C57BL ; *Microspheres ; *Polystyrenes/toxicity ; *Gastrointestinal Microbiome/drug effects ; Male ; Microplastics/toxicity ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Microplastics (MPs) have become a global environmental problem, emerging as contaminants with potentially alarming consequences. However, long-term exposure to polystyrene microspheres (PS-MS) and its effects on diet-induced obesity are not yet fully understood.<br><br>OBJECTIVES: We aimed to investigate the effect of PS-MS exposure on high-fat diet (HFD)-induced obesity and underlying mechanisms.<br><br>METHODS: In the present study, C57BL/6J mice were fed a normal diet (ND) or a HFD in the absence or presence of PS-MS via oral administration for 8 wk. Antibiotic depletion of the microbiota and fecal microbiota transplantation (FMT) were performed to assess the influence of PS-MS on intestinal microbial ecology. We performed 16S rRNA sequencing to dissect microbial discrepancies and investigated the dysbiosis-associated intestinal integrity and inflammation in serum.<br><br>RESULTS: Compared with HFD mice, mice fed the HFD with PS-MS exhibited higher body weight, liver weight, metabolic dysfunction-associated steatotic liver disease (MASLD) activity scores, and mass of white adipose tissue, as well as higher blood glucose and serum lipid concentrations. Furthermore, 16S rRNA sequencing of the fecal microbiota revealed that mice fed the HFD with PS-MS had greater &#x3b1;-diversity and greater relative abundances of Lachnospiraceae, Oscillospiraceae, Bacteroidaceae, Akkermansiaceae, Marinifilaceae, Deferribacteres, and Desulfovibrio, but lower relative abundances of Atopobiaceae, Bifidobacterium, and Parabacteroides. Mice fed the HFD with PS-MS exhibited lower expression of MUC2 mucin and higher levels of lipopolysaccharide and inflammatory cytokines [tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), interleukin-6 (IL-6), IL-1&#x3b2;, and IL-17A] in serum. Correlation analyses revealed that differences in the microbial flora of mice exposed to PS-MS were associated with obesity. Interestingly, microbiota-depleted mice did not show the same PS-MS-associated differences in Muc2 and Tjp1 expression in the distal colon, expression of inflammatory cytokines in serum, or obesity outcomes between HFD and HFD + PS-MS. Importantly, transplantation of feces from HFD + PS-MS mice to microbiota-depleted HFD-fed mice resulted in a lower expression of mucus proteins, higher expression of inflammatory cytokines, and obesity outcomes, similar to the findings in HFD + PS-MS mice.<br><br>CONCLUSIONS: Our findings provide a new gut microbiota-driven mechanism for PS-MS-induced obesity in HFD-fed mice, suggesting the need to reevaluate the adverse health effects of MPs commonly found in daily life, particularly in susceptible populations. https://doi.org/10.1289/EHP13913.}, }
@article {pmid39225491, year = {2024}, author = {Huang, H and Zhou, T and He, F and Wen, B and Yang, Y and Zhong, W and Wang, Q and Li, J}, title = {The gut microbiota improves reproductive dysfunction in obese mice by suppressing the NLRP3/ASC/caspase-1 axis.}, journal = {Future microbiology}, volume = {19}, number = {16}, pages = {1389-1405}, pmid = {39225491}, issn = {1746-0921}, support = {No. 2023YFS0280//Biao Wen/ ; No. 2022NSFSC0766//Jun Li/ ; }, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Gastrointestinal Microbiome ; Mice ; Male ; *Obesity/microbiology/metabolism ; *Caspase 1/metabolism ; *Diet, High-Fat/adverse effects ; *Fecal Microbiota Transplantation ; *Inflammasomes/metabolism ; Mice, Inbred C57BL ; Mice, Obese ; Interleukin-1beta/metabolism ; CARD Signaling Adaptor Proteins/metabolism ; Disease Models, Animal ; Reproduction ; Dietary Fiber ; Apoptosis Regulatory Proteins/metabolism ; Signal Transduction ; }, abstract = {Aim: To explore the complex relationship between gut microbiota, obesity-related male reproductive impairments, and the NLRP3 inflammasome.Methods: A high-fat diet was administered to induce obesity in a mouse model, fecal microbiota transplantation or a high-dietary fiber diet (HDFD) was administered for 5 weeks to evaluate changes in parameters related to reproductive capacity, NLRP3, gut microbiota composition and metabolites in mice.Results: A high-fat diet induces obesity and decreases reproductive capacity in male mice. Fecal microbiota transplantation and HDFD can improve reproductive capacity in obese mice by adjusting the gut microbiota population to suppress the NLRP3/ASC/caspase-1 axis, thereby reducing IL-1β levels.Conclusion: This study offers a potential treatment for obesity-induced reproductive dysfunction by targeting the gut microbiota and the NLRP3 inflammasome pathway.}, }
@article {pmid39225490, year = {2025}, author = {Pinto, S and Šajbenová, D and Benincà, E and Nooij, S and Terveer, EM and Keller, JJ and van der Meulen-de Jong, AE and Bogaards, JA and Steyerberg, EW}, title = {Dynamics of Gut Microbiota After Fecal Microbiota Transplantation in Ulcerative Colitis: Success Linked to Control of Prevotellaceae.}, journal = {Journal of Crohn's &amp; colitis}, volume = {19}, number = {2}, pages = {}, pmid = {39225490}, issn = {1876-4479}, support = {//National Institute for Public Health and the Environment (RIVM)/ ; //Vedanta Biosciences/ ; }, mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Male ; Female ; Adult ; Middle Aged ; Feces/microbiology ; Treatment Outcome ; Budesonide/therapeutic use ; Remission Induction ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an experimental treatment for ulcerative colitis (UC). We aimed to study microbial families associated with FMT treatment success.<br><br>METHODS: We analyzed stools from 24 UC patients treated with 4 FMTs weekly after randomization for pretreatment during 3 weeks with budesonide (n&#x2005;=&#x2005;12) or placebo (n&#x2005;=&#x2005;12). Stool samples were collected 9 times pre-, during, and post-FMT. Clinical and endoscopic response was assessed 14 weeks after initiation of the study using the full Mayo score. Early withdrawal due to worsening of UC symptoms was classified as non-response.<br><br>RESULTS: Nine patients (38%) reached remission at week 14, and 15 patients had a partial response or non-response at or before week 14. With a Dirichlet multinomial mixture model, we identified 5 distinct clusters based on the microbiota composition of 180 longitudinally collected patient samples and 27 donor samples. A Prevotellaceae-dominant cluster was associated with poor response to FMT treatment. Conversely, the families Ruminococcaceae and Lachnospiraceae were associated with a successful clinical response. These associations were already visible at the start of the treatment for a subgroup of patients and were retained in repeated measures analyses of family-specific abundance over time. Responders were also characterized by a significantly lower Simpson dominance compared to non-responders.<br><br>CONCLUSIONS: The success of FMT treatment of UC patients appears to be associated with specific gut microbiota families, such as control of Prevotellaceae. Monitoring the dynamics of these microbial families could potentially be used to inform treatment success early during FMT.<br><br>The study was registered in the Netherlands Trial Register, with reference number NL9858.}, }
@article {pmid39224820, year = {2024}, author = {Lin, M and Wang, P and Lu, B and Jin, M and Tan, J and Liu, W and Yuan, J and Peng, X and Chen, Y}, title = {Development and evaluation of a rapid visual loop-mediated isothermal amplification assay for the tcdA gene in Clostridioides difficile detection.}, journal = {PeerJ}, volume = {12}, number = {}, pages = {e17776}, pmid = {39224820}, issn = {2167-8359}, mesh = {*Clostridioides difficile/genetics/isolation &amp; purification ; *Nucleic Acid Amplification Techniques/methods ; Humans ; *Bacterial Toxins/genetics ; *Sensitivity and Specificity ; *Clostridium Infections/diagnosis/microbiology ; *Feces/microbiology/chemistry ; *Enterotoxins/genetics ; DNA Primers/genetics ; Molecular Diagnostic Techniques/methods ; Polymerase Chain Reaction/methods ; Adult ; Middle Aged ; }, abstract = {BACKGROUND: The tcdA gene codes for an important toxin produced by Clostridioides difficile (C. difficile), but there is currently no simple and cost-effective method of detecting it. This article establishes and validates a rapid and visual loop-mediated isothermal amplification (LAMP) assay for the detection of the tcdA gene.<br><br>METHODS: Three sets of primers were designed and optimized to amplify the tcdA gene in C. difficile using a LAMP assay. To evaluate the specificity of the LAMP assay, C. difficile VPI10463 was used as a positive control, while 26 pathogenic bacterial strains lacking the tcdA gene and distilled water were utilized as negative controls. For sensitivity analysis, the LAMP assay was compared to PCR using ten-fold serial dilutions of DNA from C. difficile VPI10463, ranging from 207 ng/&#xb5;l to 0.000207 pg/&#xb5;l. The tcdA gene of C.difficile was detected in 164 stool specimens using both LAMP and polymerase chain reaction (PCR). Positive and negative results were distinguished using real-time monitoring of turbidity and chromogenic reaction.<br><br>RESULTS: At a temperature of 66 &#xb0;C, the target DNA was successfully amplified with a set of primers designated, and visualized within 60 min. Under the same conditions, the target DNA was not amplified with the tcdA12 primers for 26 pathogenic bacterial strains that do not carry the tcdA gene. The detection limit of LAMP was 20.700 pg/&#xb5;l, which was 10 times more sensitive than that of conventional PCR. The detection rate of tcdA in 164 stool specimens using the LAMP method was 17% (28/164), significantly higher than the 10% (16/164) detection rate of the PCR method (X[2] = 47, p < 0.01).<br><br>CONCLUSION: LAMP method is an effective technique for the rapid and visual detection of the tcdA gene of C. difficile, and shows potential advantages over PCR in terms of speed, simplicity, and sensitivity. The tcdA-LAMP assay is particularly suitable for medical diagnostic environments with limited resources and is a promising diagnostic strategy for the screening and detection of C. difficile infection in populations at high risk.}, }
@article {pmid39224076, year = {2024}, author = {McMillan, AS and Theriot, CM}, title = {Bile acids impact the microbiota, host, and C. difficile dynamics providing insight into mechanisms of efficacy of FMTs and microbiota-focused therapeutics.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2393766}, pmid = {39224076}, issn = {1949-0984}, support = {R35 GM149222/GM/NIGMS NIH HHS/United States ; T32 GM133366/GM/NIGMS NIH HHS/United States ; }, mesh = {*Bile Acids and Salts/metabolism ; Humans ; *Fecal Microbiota Transplantation ; *Clostridioides difficile/physiology ; *Gastrointestinal Microbiome ; *Clostridium Infections/therapy/microbiology ; Animals ; }, abstract = {Clostridioides difficile is a major nosocomial pathogen, causing significant morbidity and mortality worldwide. Antibiotic usage, a major risk factor for Clostridioides difficile infection (CDI), disrupts the gut microbiota, allowing C. difficile to proliferate and cause infection, and can often lead to recurrent CDI (rCDI). Fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) have emerged as effective treatments for rCDI and aim to restore colonization resistance provided by a healthy gut microbiota. However, much is still unknown about the mechanisms mediating their success. Bile acids, extensively modified by gut microbes, affect C. difficile's germination, growth, and toxin production while also shaping the gut microbiota and influencing host immune responses. Additionally, microbial interactions, such as nutrient competition and cross-feeding, contribute to colonization resistance against C. difficile and may contribute to the success of microbiota-focused therapeutics. Bile acids as well as other microbial mediated interactions could have implications for other diseases being treated with microbiota-focused therapeutics. This review focuses on the intricate interplay between bile acid modifications, microbial ecology, and host responses with a focus on C. difficile, hoping to shed light on how to move forward with the development of new microbiota mediated therapeutic strategies to combat rCDI and other intestinal diseases.}, }
@article {pmid39222063, year = {2024}, author = {Shiroma, H and Darzi, Y and Terajima, E and Nakagawa, Z and Tsuchikura, H and Tsukuda, N and Moriya, Y and Okuda, S and Goto, S and Yamada, T}, title = {Enteropathway: the metabolic pathway database for the human gut microbiota.}, journal = {Briefings in bioinformatics}, volume = {25}, number = {5}, pages = {}, pmid = {39222063}, issn = {1477-4054}, support = {JPMJCR19U3//JST AIP Acceleration Research/ ; JP16H06279//Japan Society for the Promotion of Science/ ; JP21ck0106546h0002//Japan Agency for Medical Research and Development/ ; 2020-A-7//National Cancer Center Research and Development Fund/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Metabolic Networks and Pathways ; *Databases, Factual ; Software ; Computational Biology/methods ; }, abstract = {The human gut microbiota produces diverse, extensive metabolites that have the potential to affect host physiology. Despite significant efforts to identify metabolic pathways for producing these microbial metabolites, a comprehensive metabolic pathway database for the human gut microbiota is still lacking. Here, we present Enteropathway, a metabolic pathway database that integrates 3269 compounds, 3677 reactions, and 876 modules that were obtained from 1012 manually curated scientific literature. Notably, 698 modules of these modules are new entries and cannot be found in any other databases. The database is accessible from a web application (https://enteropathway.org) that offers a metabolic diagram for graphical visualization of metabolic pathways, a customization interface, and an enrichment analysis feature for highlighting enriched modules on the metabolic diagram. Overall, Enteropathway is a comprehensive reference database that can complement widely used databases, and a tool for visual and statistical analysis in human gut microbiota studies and was designed to help researchers pinpoint new insights into the complex interplay between microbiota and host metabolism.}, }
@article {pmid39218555, year = {2024}, author = {Zhang, M and Cui, Y and Liu, P and Mo, R and Wang, H and Li, Y and Wu, Y}, title = {Oat β-(1 → 3, 1 → 4)-d-glucan alleviates food allergy-induced colonic injury in mice by increasing Lachnospiraceae abundance and butyrate production.}, journal = {Carbohydrate polymers}, volume = {344}, number = {}, pages = {122535}, doi = {10.1016/j.carbpol.2024.122535}, pmid = {39218555}, issn = {1879-1344}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Colon/pathology/drug effects/metabolism ; *Butyrates/metabolism ; *Food Hypersensitivity ; *Avena/chemistry ; Clostridiales ; beta-Glucans/pharmacology/chemistry ; Mice, Inbred BALB C ; Male ; Glucans/pharmacology/chemistry ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Oat β-(1 → 3, 1 → 4)-d-glucan (OBG), a linear polysaccharide primarily found in oat bran, has been demonstrated to possess immunomodulatory properties and regulate gut microbiota. This study aimed to investigate the impact of low molecular weight (Mw) OBG (155.2 kDa) on colonic injury and allergic symptoms induced by food allergy (FA), and to explore its potential mechanism. In Experiment 1, results indicated that oral OBG improved colonic inflammation and epithelial barrier, and significantly relieved allergy symptoms. Importantly, the OBG supplement altered the gut microbiota composition, particularly increasing the abundance of Lachnospiraceae and its genera, and promoted the production of short-chain fatty acids, especially butyrate. However, in Experiment 2, the gut microbial depletion eliminated these protective effects of OBG on the colon in allergic mice. Further, in Experiment 3, fecal microbiota transplantation and sterile fecal filtrate transfer directly validated the role of OBG-mediated gut microbiota and its metabolites in relieving FA and its induced colonic injury. Our findings suggest that low Mw OBG can alleviate FA-induced colonic damage by increasing Lachnospiraceae abundance and butyrate production, and provide novel insights into the health benefits and mechanisms of dietary polysaccharide intervention for FA.}, }
@article {pmid39217880, year = {2024}, author = {Jin, Z and Liu, Z and Pan, J and Wang, S and Cui, M and He, C and Lin, M and Liu, X and Yu, X and Gong, F}, title = {FGF20 modulates gut microbiota to mitigate dextran sodium sulfate-induced ulcerative colitis in mouse models.}, journal = {International immunopharmacology}, volume = {142}, number = {Pt A}, pages = {113044}, doi = {10.1016/j.intimp.2024.113044}, pmid = {39217880}, issn = {1878-1705}, mesh = {Animals ; Mice ; *Colitis, Ulcerative/chemically induced/drug therapy/immunology/pathology ; *Colon/pathology/drug effects ; *Dextran Sulfate ; *Disease Models, Animal ; Dysbiosis/chemically induced ; Fecal Microbiota Transplantation ; *Fibroblast Growth Factors/metabolism/genetics ; *Gastrointestinal Microbiome/drug effects ; *Mice, Inbred C57BL ; *Mice, Knockout ; Female ; }, abstract = {Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), presents a significant clinical challenge due to the lack of optimal therapeutic strategies. Emerging evidence suggests that fibroblast growth factor 20 (FGF20) may play a crucial role in mitigating UC symptoms, though the mechanistic underpinnings remain elusive. In this study, a mouse model of UC was established using dextran sodium sulfate (DSS) to investigate the potential role of FGF20. Our findings revealed a marked reduction in FGF20 expression in the serum and colonic tissues of DSS-treated mice. Furthermore, FGF20 knockout did not exacerbate colonic damage in these mice. Conversely, overexpression of FGF20 via adeno-associated virus (AAV) significantly alleviated UC-associated symptoms. This alleviation was evidenced by attenuated intestinal shortening, mitigated weight loss, increased colonic goblet cell density and crypt formation, reduced inflammation severity and inflammatory cell infiltration, and enhanced expression of tight junction and mucin proteins. Moreover, FGF20 significantly ameliorated the dysbiosis of gut microbiota in DSS-treated mice by increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria. The beneficial effects of FGF20 were notably attenuated following gut microbiota depletion with an antibiotic regimen. Fecal microbiota transplantation experiments further supported the critical role of gut microbiota in mediating the effects of FGF20 on DSS-treated mice. In conclusion, these findings highlight the potential involvement of gut microbiota in the therapeutic effects of FGF20 in UC.}, }
@article {pmid39217582, year = {2024}, author = {Yang, Q and Wang, Z and Liu, M and Gan, L}, title = {Causal Relationship Between Gut Microbiota and Leukemia: Future Perspectives.}, journal = {Oncology and therapy}, volume = {12}, number = {4}, pages = {663-683}, pmid = {39217582}, issn = {2366-1089}, abstract = {The gut microbiota plays a crucial role in maintaining homeostasis in the human gastrointestinal tract. Numerous studies have shown a strong association between the gut microbiota and the emergence and progression of various diseases. Leukemia is one of the most common hematologic malignancies. Although standardized protocols and expert consensus have been developed for routine diagnosis and treatment, limitations remain due to individual differences. Nevertheless, a large number of studies have established a link between the gut microbiota and leukemia, with disturbances in the gut microbiota directly or indirectly affecting the development of leukemia. However, the causal relationship between the two remains unclear, and studying and exploring the causal relationship may open up entirely new avenues and protocols for use in the prevention and/or treatment of leukemia, offering new insights into diagnosis and treatment. In this review, the intricate relationship between the gut microbiota and leukemia is explored in depth, including causal associations, metabolite effects, therapeutic applications, and complications. Based on the characteristics of the gut microbiota, the future applications and prospects of gut microbiota are discussed to provide useful information for clinical treatment of leukemia.}, }
@article {pmid39217051, year = {2024}, author = {Akhmedov, M and Espinoza, JL}, title = {Addressing the surge of infections by multidrug-resistant Enterobacterales in hematopoietic cell transplantation.}, journal = {Blood reviews}, volume = {68}, number = {}, pages = {101229}, doi = {10.1016/j.blre.2024.101229}, pmid = {39217051}, issn = {1532-1681}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Drug Resistance, Multiple, Bacterial ; *Enterobacteriaceae Infections/microbiology/drug therapy/etiology/epidemiology/therapy ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Enterobacteriaceae/drug effects ; Infection Control/methods ; Fecal Microbiota Transplantation ; Disease Management ; }, abstract = {Patients undergoing hematopoietic cell transplantation (HCT) have an increased risk of developing severe infections. In recent years, bloodstream infections caused by Gram-negative bacteria have been increasingly reported among HCT recipients, and many of these infections are caused by bacterial strains of the Enterobacterales order. Among these pathogens, particularly concerning are the multidrug-resistant Enterobacterales (MDRE), such as Extended Spectrum β-lactamase-producing Enterobacterales and Carbapenem-resistant Enterobacterales, since infections caused by these pathogens are difficult to treat due to the limited antimicrobial options and are associated with worse transplant outcomes. We summarized the evidence from studies published in PubMed and Scopus on the burden of MDRE infections in HCT recipients, and strategies for the management and prevention of these infections, including strict adherence to recommended infection control practices and multidisciplinary antimicrobial stewardship, the use of probiotics, and fecal microbiota transplantation, are also discussed.}, }
@article {pmid39212186, year = {2024}, author = {Junker Mentzel, CM and Hui, Y and Hammerich, TMS and Klug-Dambmann, M and Liu, Y and Zachariassen, LF and Hansen, LH and Aslampaloglou, A and Kiersgaard, M and Nielsen, DS and Hansen, AK and Krych, L}, title = {Low-gainer diet-induced obese microbiota transplanted mice exhibit increased fighting.}, journal = {Clinical and translational science}, volume = {17}, number = {9}, pages = {e13906}, pmid = {39212186}, issn = {1752-8062}, support = {//LIFEPHARM/ ; //Novo Nordisk A/S/ ; //Center for Applied Laboratory Animal Research/ ; }, mesh = {Animals ; Male ; *Obesity/microbiology/etiology ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Mice, Inbred C57BL ; *Diet, High-Fat/adverse effects ; *Weight Gain ; Mice ; Disease Models, Animal ; Leptin/blood/metabolism ; Feces/microbiology ; }, abstract = {Weight gain variation is a great challenge in diet-induced obesity studies since low-gainer animals are of limited experimental value. The inbred C57BL/6 (B6) mice are frequently used models due to their genetic homogeneity and susceptibility to diet-induced obesity (DIO). The aim of this study is to investigate if the gut microbiota (GM) influences the fraction of low weight gainers in DIO studies. A total of 100 male B6 mice (donor population) were fed a high-fat diet for 14 weeks and divided into the study groups high gainer (HG) and low gainer (LG) based on their weight gain. Subsequently, fecal matter transplantation (FMT) was done on germ-free B6 mice with GM from HG and LG donors (FMT population). LG (13.35 ± 2.5 g) and HG (25.52 ± 2.0 g) animals were identified by the weight gain from week 1 to week 12. Interestingly, the start weight of the LG (20.36 ± 1.4 g) and HG (21.59 ± 0.7 g) groups differed significantly. Transplanting LG or HG fecal matter to germ-free mice resulted in significant differences in weight gain between HG and LG, as well as differences in serum leptin levels and epididymal fat pad weight. A clear LG-specific GM composition could not be distinguished by 16S rRNA gene amplicon sequencing. Surprisingly, significantly more fighting was recorded in LG groups of both donor populations and when transplanted to germ-free mice. The HG and LG phenotypes could be transferred to germ-free mice. The increased fighting in the LG group in both studies suggests not only that the tendency to fight can be transferred by FMT in these mice, but also that fighting should be prevented in DIO studies to minimize the number of LG animals.}, }
@article {pmid39214188, year = {2025}, author = {Hensen, ADO and Vehreschild, MJGT and Gerding, DN and Krut, O and Chen, W and Young, VB and Tzipori, S and Solbach, P and Gibani, MM and Chiu, C and de Keersmaecker, SCJ and Dasyam, D and Morel, S and Devaster, JM and Corti, N and Kuijper, EJ and Roestenberg, M and Smits, WK}, title = {How to develop a controlled human infection model for Clostridioides difficile.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {31}, number = {3}, pages = {373-379}, doi = {10.1016/j.cmi.2024.08.025}, pmid = {39214188}, issn = {1469-0691}, mesh = {Humans ; *Clostridioides difficile/pathogenicity ; *Clostridium Infections/microbiology ; Fecal Microbiota Transplantation ; Healthy Volunteers ; }, abstract = {BACKGROUND: Clostridioides difficile (C. difficile) remains the leading cause of healthcare-associated diarrhoea, posing treatment challenges because of antibiotic resistance and high relapse rates. Faecal microbiota transplantation is a novel treatment strategy to prevent relapses of C. difficile infection (CDI), however, the exact components conferring colonization resistance are unknown, hampering its translation to a medicinal product. The development of novel products independent of antibiotics, which increase colonization resistance or induce protective immune mechanisms is urgently needed.<br><br>OBJECTIVES: To establish a framework for a Controlled Human Infection Model (CHIM) of C.&#xa0;difficile, in which healthy volunteers are exposed to toxigenic C.&#xa0;difficile spores, offering the possibility to test novel approaches and identify microbiota and immunological targets. Whereas experimental exposure to non-toxigenic C.&#xa0;difficile has been done before, a toxigenic C.&#xa0;difficile CHIM faces ethical, scientific, logistical, and biosafety challenges.<br><br>SOURCES: Specific challenges in developing a C.&#xa0;difficile CHIM were discussed by a group of international experts during a workshop organized by Inno4Vac, an Innovative Health Initiative-funded consortium.<br><br>CONTENT: The experts agreed that the main challenges are: developing a clinically relevant CHIM that induces mild to moderate CDI symptoms but not severe CDI, determining the optimal C.&#xa0;difficile inoculum dose, and understanding the timing and duration of antibiotic pretreatment in inducing susceptibility to CDI in healthy volunteers.<br><br>IMPLICATIONS: Should these challenges be tackled, a C.&#xa0;difficile CHIM will not only provide a way forward for the testing of novel products but also offer a framework for a better understanding of the pathophysiology, pathogenesis, and immunology of C.&#xa0;difficile colonization and infection.}, }
@article {pmid39214085, year = {2024}, author = {Hayase, E and Hayase, T and Mukherjee, A and Stinson, SC and Jamal, MA and Ortega, MR and Sanchez, CA and Ahmed, SS and Karmouch, JL and Chang, CC and Flores, II and McDaniel, LK and Brown, AN and El-Himri, RK and Chapa, VA and Tan, L and Tran, BQ and Xiao, Y and Fan, C and Pham, D and Halsey, TM and Jin, Y and Tsai, WB and Prasad, R and Glover, IK and Enkhbayar, A and Mohammed, A and Schmiester, M and King, KY and Britton, RA and Reddy, P and Wong, MC and Ajami, NJ and Wargo, JA and Shelburne, S and Okhuysen, PC and Liu, C and Fowler, SW and Conner, ME and Katsamakis, Z and Smith, N and Burgos da Silva, M and Ponce, DM and Peled, JU and van den Brink, MRM and Peterson, CB and Rondon, G and Molldrem, JJ and Champlin, RE and Shpall, EJ and Lorenzi, PL and Mehta, RS and Martens, EC and Alousi, AM and Jenq, RR}, title = {Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {9}, pages = {1621-1636.e6}, pmid = {39214085}, issn = {1934-6069}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R35 HL155672/HL/NHLBI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; P01 HL170046/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 HL158796/HL/NHLBI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; }, mesh = {*Graft vs Host Disease/microbiology ; Animals ; *Bacteroides/drug effects ; *Gastrointestinal Microbiome/drug effects ; Mice ; Humans ; Female ; Male ; Dysbiosis/microbiology ; Feces/microbiology ; Hematopoietic Stem Cell Transplantation ; Disease Models, Animal ; Mice, Inbred C57BL ; Middle Aged ; Akkermansia ; Adult ; Bacteroides thetaiotaomicron/drug effects ; Mice, Inbred BALB C ; }, abstract = {Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.}, }
@article {pmid39213702, year = {2024}, author = {Su, Y and Fan, X and Cai, X and Ning, J and Shen, M}, title = {Effects of fecal microbiota transplantation combined with selenium on intestinal microbiota in mice with colorectal cancer.}, journal = {Biochemical and biophysical research communications}, volume = {733}, number = {}, pages = {150580}, doi = {10.1016/j.bbrc.2024.150580}, pmid = {39213702}, issn = {1090-2104}, mesh = {Animals ; *Colorectal Neoplasms/microbiology/therapy/metabolism/pathology ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation ; Mice ; *Sodium Selenite/pharmacology ; Selenium/pharmacology ; Male ; Mice, Inbred C57BL ; Combined Modality Therapy ; }, abstract = {Colorectal cancer (CRC) is the third most common cancer in the world. With the development of high-throughput gene sequencing technology, homeostasis imbalance of the intestinal microbiota has been proven to play a key role in the pathogenesis of CRC. Furthermore, fecal bacteria transplantation (FMT) has been shown to alter the intestinal microecology, and is potentially an effective treatment for CRC. Sodium selenite plays an important role in anticancer adjuvant therapy due to its high pro-oxidation characteristics. In this study, a murine CRC tumor model was induced by AOM/DSS, and CRC mice were treated by FMT, sodium selenite, and FMT combined with sodium selenite. The results showed that FMT, sodium selenite, and FMT combined with sodium selenite inhibited the occurrence of CRC in mice, increased the abundance of beneficial intestinal bacteria, produced different microorganisms, and changed the metabolic pathways of the intestinal microbiota. In summary, FMT, sodium selenite, and FMT combined with sodium selenite can inhibit the occurrence of CRC by increasing the abundance of beneficial bacteria and regulating phenotypes and metabolic pathways. Notably, the effect of FMT combined with sodium selenite in reducing the number of tumors, protecting intestinal tissues, and restoring the diversity and richness of the intestinal microbiota is superior to that of FMT alone or sodium selenite alone. The results of this study provide new ideas for the application of FMT and selenium in the treatment of CRC.}, }
@article {pmid39212377, year = {2024}, author = {Pan, L and Yin, N and Duan, M and Mei, Q and Zeng, Y}, title = {The role of gut microbiome and its metabolites in pancreatitis.}, journal = {mSystems}, volume = {9}, number = {10}, pages = {e0066524}, pmid = {39212377}, issn = {2379-5077}, support = {81970555//MOST | National Natural Science Foundation of China (NSFC)/ ; 82200714//MOST | National Natural Science Foundation of China Youth Fund (NSFC)/ ; 82270671//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Pancreatitis/metabolism/microbiology ; Animals ; }, abstract = {Gut microbiome plays a vital role in the intestinal ecosystem and has close association with metabolites. Due to the development of metabolomics and microbiomics, recent studies have observed that alteration of either the gut microbiome or metabolites may have effects on the progression of pancreatitis. Several new treatments based on the gut microbiome or metabolites have been studied extensively in recent years. Gut microbes, such as Bifidobacterium, Akkermansia, and Lactobacillus, and metabolites, such as short-chain fatty acids, bile acids, vitamin, hydrogen sulfide, and alcohol, have different effects on pancreatitis. Some preliminary studies about new intervention measures were based on the gut microbiome and metabolites such as diet, prebiotic, herbal medicine, and fecal microbiota transplantation. This review aims to summarize the recent advances about the gut microbiome, metabolites, and pancreatitis in order to determine the potential beneficial role of the gut microbiome and metabolites in pancreatitis.}, }
@article {pmid39212113, year = {2025}, author = {Liu, Z and Wang, M and Hu, Y and Li, J and Gong, W and Guo, X and Song, S and Zhu, B}, title = {Ulva lactuca polysaccharides combined with fecal microbiota transplantation ameliorated dextran sodium sulfate-induced colitis in C57BL/6J mice.}, journal = {Journal of the science of food and agriculture}, volume = {105}, number = {1}, pages = {422-432}, doi = {10.1002/jsfa.13839}, pmid = {39212113}, issn = {1097-0010}, support = {2023YFD2100200//National Key Research and Development Program of China/ ; 32302148//National Natural Science Foundation of China/ ; ZDSYS20220117155800001//Shenzhen Science and Technology Program/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Mice, Inbred C57BL ; Mice ; *Dextran Sulfate/adverse effects ; *Polysaccharides/administration &amp; dosage ; *Gastrointestinal Microbiome ; Male ; Humans ; *Feces/microbiology ; *Ulva/chemistry ; *Colitis, Ulcerative/therapy/chemically induced/microbiology ; Plant Extracts/administration &amp; dosage ; Colitis/chemically induced/therapy/microbiology ; Bacteria/classification/isolation &amp; purification/genetics ; Disease Models, Animal ; Edible Seaweeds ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) of healthy donors improves ulcerative colitis (UC) patients by restoring the balance of the gut microbiota. However, donors vary in microbial diversity and composition, often resulting in weak or even ineffective FMT. Improving the efficacy of FMT through combination treatment has become a promising strategy. Ulva lactuca polysaccharides (ULP) have been found to benefit host health by regulating gut microbiota. The effect of the combination of ULP and FMT in ameliorating UC has not yet been evaluated.<br><br>RESULTS: The present study found that supplementation with ULP combined with FMT showed better effects in ameliorating UC than supplementation with FMT alone. Results suggested that FMT or ULP combined with FMT alleviated the symptoms of UC in mice, as evidenced by prevention of body weight loss, improvement of disease activity index and protection of the intestinal mucus. Notably, ULP in combination with FMT was more effective than FMT in reducing levels of cytokines and related inflammatory enzymes. In addition, ULP combined with FMT effectively restored the dysbiosis induced by dextran sulfate sodium (DSS) and further enriched probiotics (such as Bifidobacterium). The production of short-chain fatty acids, especially acetic acid, was also significantly enriched by ULP combined with FMT.<br><br>CONCLUSION: Supplementation of ULP combined with FMT could significantly ameliorate DSS-induced colitis in mice by inhibiting inflammation and restoring dysbiosis of gut microbiota. These results suggested that ULP combined with FMT has potential application in ameliorating UC. &#xa9; 2024 Society of Chemical Industry.}, }
@article {pmid39211181, year = {2024}, author = {Kennedy, MS and Freiburger, A and Cooper, M and Beilsmith, K and St George, ML and Kalski, M and Cham, C and Guzzetta, A and Ng, SC and Chan, FK and Rubin, D and Henry, CS and Bergelson, J and Chang, EB}, title = {Diet outperforms microbial transplant to drive microbiome recovery post-antibiotics.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.08.01.606245}, pmid = {39211181}, issn = {2692-8205}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; }, abstract = {High-fat, low-fiber Western-style diets (WD) induce microbiome dysbiosis characterized by reduced taxonomic diversity and metabolic breadth, which in turn increases risk for a wide array of metabolic, immune and systemic pathologies. Recent work has established that WD can impair microbiome resilience to acute perturbations like antibiotic treatment, although we know little about the mechanism of impairment and the specific host consequences of prolonged post-antibiotic dysbiosis. Here, we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) and WD, and find that only mice on RC undergo a rapid successional process of recovery. Metabolic modeling indicates that RC diet promotes the development of syntrophic cross-feeding interactions, while on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither. Furthermore, prolonged post-antibiotic dysbiosis in mice on WD renders them susceptible to infection by the intestinal pathogen Salmonella enterica serovar Typhimurium. Our data challenge widespread enthusiasm for fecal microbiota transplant (FMT) as a strategy to address dysbiosis and demonstrate that specific dietary interventions are, at minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural, and less invasive alternative to FMT.}, }
@article {pmid39210613, year = {2024}, author = {Xu, Y and Wu, X and Li, Y and Liu, X and Fang, L and Jiang, Z}, title = {Probiotics and the Role of Dietary Substrates in Maintaining the Gut Health: Use of Live Microbes and Their Products for Anticancer Effects against Colorectal Cancer.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {10}, pages = {1933-1946}, pmid = {39210613}, issn = {1738-8872}, mesh = {*Probiotics/therapeutic use ; *Colorectal Neoplasms/microbiology ; Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Animals ; Diet ; Bacteria/classification/genetics/metabolism ; Gastrointestinal Tract/microbiology ; Bifidobacterium ; Antineoplastic Agents ; }, abstract = {The gut microbiome is an important and the largest endocrine organ linked to the microbes of the GI tract. The bacterial, viral and fungal communities are key regulators of the health and disease status in a host at hormonal, neurological, immunological, and metabolic levels. The useful microbes can compete with microbes exhibiting pathogenic behavior by maintaining resistance against their colonization, thereby maintaining eubiosis. As diagnostic tools, metagenomic, proteomic and genomic approaches can determine various microbial markers in clinic for early diagnosis of colorectal cancer (CRC). Probiotics are live non-pathogenic microorganisms such as lactic acid bacteria, Bifidobacteria, Firmicutes and Saccharomyces that can help maintain eubiosis when administered in appropriate amounts. In addition, the type of dietary intake contributes substantially to the composition of gut microbiome. The use of probiotics has been found to exert antitumor effects at preclinical levels and promote the antitumor effects of immunotherapeutic drugs at clinical levels. Also, modifying the composition of gut microbiota by Fecal Microbiota Transplantation (FMT), and using live lactic acid producing bacteria such as Lactobacillus, Bifidobacteria and their metabolites (termed postbiotics) can contribute to immunomodulation of the tumor microenvironment. This can lead to tumor-preventive effects at early stages and antitumor effects after diagnosis of CRC. To conclude, probiotics are presumably found to be safe to use in humans and are to be studied further to promote their appliance at clinical levels for management of CRC.}, }
@article {pmid39206530, year = {2024}, author = {Gupta, CL and Jaganathasamy, N and Madkaikar, M}, title = {Microbiome in sickle cell disease: Pathophysiology and therapeutic insights.}, journal = {British journal of haematology}, volume = {205}, number = {4}, pages = {1279-1287}, doi = {10.1111/bjh.19736}, pmid = {39206530}, issn = {1365-2141}, mesh = {*Anemia, Sickle Cell/therapy/microbiology/complications/physiopathology ; Humans ; *Gastrointestinal Microbiome ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Sickle cell disease (SCD) is a complex genetic blood disorder characterized by abnormal haemoglobin, resulting in sickle-shaped red blood cells. While extensive research has concentrated on the genetic and physiological aspects of SCD, recent studies suggest a potential role of the human microbiome in SCD pathophysiology, adding new dimensions to its understanding. This review synthesizes current knowledge on the microbiome's involvement in SCD, focusing on alterations in the gut microbiome composition and diversity compared to healthy individuals, and their implications for disease pathogenesis. We explore how microbiome changes may contribute to vaso-occlusive crises and other complications, along with the possible associations of specific microbial taxa or markers with disease crises and clinical outcomes. Additionally, we discuss the potential of microbiome-targeted interventions, including probiotics, dietary modifications, and faecal microbiota transplantation, in managing SCD complications and improving patient outcomes. Understanding the intricate relationship between the microbiome and SCD could lead to innovative therapeutic strategies and personalized interventions for better managing the disease. This review underscores the importance of further microbiome research and its integration into holistic SCD care.}, }
@article {pmid39205822, year = {2024}, author = {Hosseini-Asl, SMK and Mehrabani, G and Masoumi, SJ}, title = {Key Focus Areas in Pouchitis Therapeutic Status: A Narrative Review.}, journal = {Iranian journal of medical sciences}, volume = {49}, number = {8}, pages = {472-486}, pmid = {39205822}, issn = {1735-3688}, mesh = {Humans ; *Pouchitis/therapy/etiology/drug therapy ; Fecal Microbiota Transplantation/methods ; Probiotics/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Pouchitis, as the most common complication after ileal pouch-anal anastomosis (IPAA), has an incidence from 7% to 46%. Pouchitis treatment still represents one of the biggest gaps of knowledge in the treatment of diseases. This review has focused on achievements and challenges in the treatment of pouchitis. A combined assessment of symptoms, endoscopic findings, histologic results, quick biomarkers, and fecal calprotectin test were determined to be valuable diagnostic criteria. Conventional therapy was described as a modification of bacterial flora, mainly with antibiotics and more recently with probiotics such as bifidobacteria, lactobacilli, and streptococci. Other therapeutic approaches such as anti-tumor necrosis factor, infliximab, adalimumab, vedolizumab, ustekinumab, tacrolimus, tofacitinib, thiopurines, corticosteroids, prolyl hydroxylase-containing enzymes, povidone-iodine, dextrose spray, fecal microbiota transplantation, herbal medicines, and leukocyte apheresis have been discussed. Changes in dietary components, and administration of complementary and alternative medicine, probiotics, and fecal transplantation in addition to conventional therapies were also shown to affect the outcome of disease. Due to the potential significant impairment in quality of life caused by pouchitis, it is essential to address the gaps in knowledge for both patients and physicians in its treatment. Therefore, well-designed and adequately powered studies should assess the optimal treatment for pouchitis.}, }
@article {pmid39205654, year = {2024}, author = {Wu, L and Zhou, J and Zhou, A and Lei, Y and Tang, L and Hu, S and Wang, S and Xiao, X and Chen, Q and Tu, D and Lu, C and Lai, Y and Li, Y and Zhang, X and Tang, B and Yang, S}, title = {Lactobacillus acidophilus ameliorates cholestatic liver injury through inhibiting bile acid synthesis and promoting bile acid excretion.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2390176}, pmid = {39205654}, issn = {1949-0984}, mesh = {*Lactobacillus acidophilus ; *Bile Acids and Salts/metabolism ; Animals ; *Gastrointestinal Microbiome ; *Cholestasis/metabolism/microbiology ; Mice ; Humans ; Male ; *Probiotics/pharmacology/administration &amp; dosage ; *Liver/metabolism ; *Mice, Inbred C57BL ; Feces/microbiology ; Cholesterol 7-alpha-Hydroxylase/metabolism/genetics ; Female ; Fibroblast Growth Factors/metabolism/genetics ; Fecal Microbiota Transplantation ; Dysbiosis/microbiology/therapy ; RNA, Ribosomal, 16S/genetics ; Middle Aged ; Adult ; Disease Models, Animal ; Ileum/microbiology/metabolism ; }, abstract = {Gut microbiota dysbiosis is involved in cholestatic liver diseases. However, the mechanisms remain to be elucidated. The purpose of this study was to examine the effects and mechanisms of Lactobacillus acidophilus (L. acidophilus) on cholestatic liver injury in both animals and humans. Bile duct ligation (BDL) was performed to mimic cholestatic liver injury in mice and serum liver function was tested. Gut microbiota were analyzed by 16S rRNA sequencing. Fecal bacteria transplantation (FMT) was used to evaluate the role of gut microbiota in cholestasis. Bile acids (BAs) profiles were analyzed by targeted metabolomics. Effects of L. acidophilus in cholestatic patients were evaluated by a randomized controlled clinical trial (NO: ChiCTR2200063330). BDL induced different severity of liver injury, which was associated with gut microbiota. 16S rRNA sequencing of feces confirmed the gut flora differences between groups, of which L. acidophilus was the most distinguished genus. Administration of L. acidophilus after BDL significantly attenuated hepatic injury in mice, decreased liver total BAs and increased fecal total BAs. Furthermore, after L. acidophilus treatment, inhibition of hepatic Cholesterol 7α-hydroxylase (CYP7α1), restored ileum Fibroblast growth factor 15 (FGF15) and Small heterodimer partner (SHP) accounted for BAs synthesis decrease, whereas enhanced BAs excretion was attributed to the increase of unconjugated BAs by enriched bile salt hydrolase (BSH) enzymes in feces. Similarly, in cholestasis patients, supplementation of L. acidophilus promoted the recovery of liver function and negatively correlated with liver function indicators, possibly in relationship with the changes in BAs profiles and gut microbiota composition. L. acidophilus treatment ameliorates cholestatic liver injury through inhibited hepatic BAs synthesis and enhances fecal BAs excretion.}, }
@article {pmid39204246, year = {2024}, author = {Spigaglia, P}, title = {Clostridioides difficile and Gut Microbiota: From Colonization to Infection and Treatment.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {39204246}, issn = {2076-0817}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Clostridioides difficile/pathogenicity ; *Clostridium Infections/therapy/microbiology ; *Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use/adverse effects ; Diarrhea/microbiology/therapy ; }, abstract = {Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea (AAD) in hospitals in the developed world. Both infected patients and asymptomatic colonized individuals represent important transmission sources of C. difficile. C. difficile infection (CDI) shows a large range of symptoms, from mild diarrhea to severe manifestations such as pseudomembranous colitis. Epidemiological changes in CDIs have been observed in the last two decades, with the emergence of highly virulent types and more numerous and severe CDI cases in the community. C. difficile interacts with the gut microbiota throughout its entire life cycle, and the C. difficile's role as colonizer or invader largely depends on alterations in the gut microbiota, which C. difficile itself can promote and maintain. The restoration of the gut microbiota to a healthy state is considered potentially effective for the prevention and treatment of CDI. Besides a fecal microbiota transplantation (FMT), many other approaches to re-establishing intestinal eubiosis are currently under investigation. This review aims to explore current data on C. difficile and gut microbiota changes in colonized individuals and infected patients with a consideration of the recent emergence of highly virulent C. difficile types, with an overview of the microbial interventions used to restore the human gut microbiota.}, }
@article {pmid39203805, year = {2024}, author = {Deleu, S and Jacobs, I and Vazquez Castellanos, JF and Verstockt, S and Trindade de Carvalho, B and Subotić, A and Verstockt, B and Arnauts, K and Deprez, L and Vissers, E and Lenfant, M and Vandermeulen, G and De Hertogh, G and Verbeke, K and Matteoli, G and Huys, GRB and Thevelein, JM and Raes, J and Vermeire, S}, title = {Effect of Mutant and Engineered High-Acetate-Producing Saccharomyces cerevisiae var. boulardii Strains in Dextran Sodium Sulphate-Induced Colitis.}, journal = {Nutrients}, volume = {16}, number = {16}, pages = {}, pmid = {39203805}, issn = {2072-6643}, support = {VR 2021 1712 DOC. 1492/4//Grand Challenges Program of VIB/ ; }, mesh = {Animals ; *Dextran Sulfate ; Female ; *Acetates ; Mice ; *Saccharomyces cerevisiae/genetics ; *Colitis/chemically induced/therapy ; *Probiotics ; Disease Models, Animal ; Colon/metabolism/microbiology/pathology ; Saccharomyces boulardii ; Colitis, Ulcerative/chemically induced/therapy/microbiology ; Mutation ; Gastrointestinal Microbiome ; Feces/microbiology ; Mice, Inbred C57BL ; }, abstract = {Acetate-producing Saccharomyces cerevisiae var. boulardii strains could exert improved effects on ulcerative colitis, which here, was preclinically evaluated in an acute dextran sodium sulphate induced model of colitis. Nine-week-old female mice were divided into 12 groups, receiving either drinking water or 2.75% dextran sodium sulphate for 7 days, combined with a daily gavage of various treatments with different levels of acetate accumulation: sham control (phosphate buffered saline, no acetate), non-probiotic control (Baker's yeast, no acetate), probiotic control (Enterol[®], transient acetate), and additionally several Saccharomyces cerevisiae var. boulardii strains with respectively no, high, and extra-high acetate accumulation. Disease activity was monitored daily, and feces samples were collected at different timepoints. On day 14, the mice were sacrificed, upon which blood and colonic tissue were collected for analysis. Disease activity in inflamed mice was lower when treated with the high-acetate-producing strain compared to sham and non-probiotic controls. The non-acetate-producing strain showed higher disease activity compared to the acetate-producing strains. Accordingly, higher histologic inflammation was observed in non- or transient-acetate-producing strains compared to the sham control, whereas this increase was not observed for high- and extra-high-acetate-producing strains upon induction of inflammation. These anti-inflammatory findings were confirmed by transcriptomic analysis of differentially expressed genes. Moreover, only the strain with the highest acetate production was superior in maintaining a stable gut microbial alpha-diversity upon inflammation. These findings support new possibilities for acetate-mediated management of inflammation in inflammatory bowel disease by administrating high-acetate-producing Saccharomyces cerevisae var. boulardii strains.}, }
@article {pmid39203583, year = {2024}, author = {Yamada, CH and Ortis, GB and Buso, GM and Martins, TC and Zequinao, T and Telles, JP and Wollmann, LC and Montenegro, CO and Dantas, LR and Cruz, JW and Tuon, FF}, title = {Validation of Lyophilized Human Fecal Microbiota for the Treatment of Clostridioides difficile Infection: A Pilot Study with Pharmacoeconomic Analysis of a Middle-Income Country-Promicrobioma Project.}, journal = {Microorganisms}, volume = {12}, number = {8}, pages = {}, pmid = {39203583}, issn = {2076-2607}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) represents a prevalent and potentially severe health concern linked to the usage of broad-spectrum antibiotics. The aim of this study was to evaluate a new lyophilized product based on human fecal microbiota for transplant, including cost-benefit analysis in the treatment of recurrent or refractory CDI.<br><br>METHODS: The product for fecal microbiota transplant was obtained from two donors. Microbiological, viability, and genomic analysis were evaluated. After validation, a clinical pilot study including recurrent or refractory CDI with 24 patients was performed. Clinical response and 4-week recurrence were the outcome. Cost-benefit analysis compared the fecal microbiota transplant with conventional retreatment with vancomycin or metronidazole.<br><br>RESULTS: The microbiota for transplant presented significant bacterial viability, with and adequate balance of Firmicutes and Bacteroidetes. The clinical response with the microbiota transplant was 92%. In financial terms, estimated expenditure for CDI solely related to recurrence, based on stochastic modeling, totals USD 222.8 million per year in Brazil.<br><br>CONCLUSIONS: The lyophilized human fecal microbiota for transplant is safe and can be an important step for a new product with low cost, even with genomic sequencing. Fecal microbiota transplantation emerges as a more cost-effective alternative compared to antimicrobials in the retreatment of CDI.}, }
@article {pmid39200335, year = {2024}, author = {Zikou, E and Koliaki, C and Makrilakis, K}, title = {The Role of Fecal Microbiota Transplantation (FMT) in the Management of Metabolic Diseases in Humans: A Narrative Review.}, journal = {Biomedicines}, volume = {12}, number = {8}, pages = {}, pmid = {39200335}, issn = {2227-9059}, abstract = {The gut microbiota represents a complex ecosystem of trillions of microorganisms residing in the human gastrointestinal tract, which is known to interact with the host physiology and regulate multiple functions. Alterations in gut microbial composition, diversity, and function are referred to as dysbiosis. Dysbiosis has been associated with a variety of chronic diseases, including Clostridioides difficile infections, but also cardiometabolic diseases, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). The implication of gut microbiota dysbiosis in the pathogenesis of both obesity and T2DM has paved the way to implementing novel therapeutic approaches for metabolic diseases through gut microbial reconfiguration. These interventions include probiotics, prebiotics, and synbiotics, while a more innovative approach has been fecal microbiota transplantation (FMT). FMT is a procedure that delivers healthy human donor stool to another individual through the gastrointestinal tract, aiming to restore gut microbiota balance. Several studies have investigated this approach as a potential tool to mitigate the adverse metabolic effects of gut microbiota aberrations associated with obesity and T2DM. The aim of the present review was to critically summarize the existing evidence regarding the clinical applications of FMT in the management of obesity and T2DM and provide an update on the potential of this method to remodel the entire host microbiota, leading thus to weight loss and sustained metabolic benefits. Safety issues, long-term efficacy, limitations, and pitfalls associated with FMT studies are further discussed, emphasizing the need for further research and standardization in certain methodological aspects in order to optimize metabolic outcomes.}, }
@article {pmid39200203, year = {2024}, author = {Kerstens, R and Joyce, P}, title = {The Gut Microbiome as a Catalyst and Emerging Therapeutic Target for Parkinson's Disease: A Comprehensive Update.}, journal = {Biomedicines}, volume = {12}, number = {8}, pages = {}, pmid = {39200203}, issn = {2227-9059}, support = {2022-CF-EMCR-004-25314//Hospital Research Foundation/ ; }, abstract = {Parkinson's Disease is the second most prevalent neurological disorder globally, and its cause is still largely unknown. Likewise, there is no cure, and existing treatments do little more than subdue symptoms before becoming ineffective. It is increasingly important to understand the factors contributing to Parkinson's Disease aetiology so that new and more effective pharmacotherapies can be established. In recent years, there has been an emergence of research linking gut dysbiosis to Parkinson's Disease via the gut-brain axis. Advancements in microbial profiling have led to characterisation of a Parkinson's-specific microbial signature, where novel treatments that leverage and correct gut dysbiosis are beginning to emerge for the safe and effective treatment of Parkinson's Disease. Preliminary clinical studies investigating microbiome-targeted therapeutics for Parkinson's Disease have revealed promising outcomes, and as such, the aim of this review is to provide a timely and comprehensive update of the most recent advances in this field. Faecal microbiota transplantation has emerged as a novel and potential frontrunner for microbial-based therapies due to their efficacy in alleviating Parkinson's Disease symptomology through modulation of the gut-brain axis. However, more rigorous clinical investigation, along with technological advancements in diagnostic and in vitro testing tools, are critically required to facilitate the widespread clinical translation of microbiome-targeting Parkinson's Disease therapeutics.}, }
@article {pmid39199404, year = {2024}, author = {Fu, Y and Cheng, HW}, title = {The Influence of Cecal Microbiota Transplantation on Chicken Injurious Behavior: Perspective in Human Neuropsychiatric Research.}, journal = {Biomolecules}, volume = {14}, number = {8}, pages = {}, pmid = {39199404}, issn = {2218-273X}, support = {2017-67015-26567//NIFA-AFRI, USDA/ ; }, mesh = {Animals ; *Chickens ; Humans ; *Gastrointestinal Microbiome ; Brain-Gut Axis ; Behavior, Animal ; Fecal Microbiota Transplantation ; Aggression ; Cecum/microbiology ; Mental Disorders/etiology/microbiology ; Stress, Psychological/microbiology ; Dysbiosis/microbiology ; }, abstract = {Numerous studies have evidenced that neuropsychiatric disorders (mental illness and emotional disturbances) with aggression (or violence) pose a significant challenge to public health and contribute to a substantial economic burden worldwide. Especially, social disorganization (or social inequality) associated with childhood adversity has long-lasting effects on mental health, increasing the risk of developing neuropsychiatric disorders. Intestinal bacteria, functionally as an endocrine organ and a second brain, release various immunomodulators and bioactive compounds directly or indirectly regulating a host's physiological and behavioral homeostasis. Under various social challenges, stress-induced dysbiosis increases gut permeability causes serial reactions: releasing neurotoxic compounds, leading to neuroinflammation and neuronal injury, and eventually neuropsychiatric disorders associated with aggressive, violent, or impulsive behavior in humans and various animals via a complex bidirectional communication of the microbiota-gut-brain (MGB) axis. The dysregulation of the MGB axis has also been recognized as one of the reasons for the prevalence of social stress-induced injurious behaviors (feather pecking, aggression, and cannibalistic pecking) in chickens. However, existing knowledge of preventing and treating these disorders in both humans and chickens is not well understood. In previous studies, we developed a non-mammal model in an abnormal behavioral investigation by rationalizing the effects of gut microbiota on injurious behaviors in chickens. Based on our earlier success, the perspective article outlines the possibility of reducing stress-induced injurious behaviors in chickens through modifying gut microbiota via cecal microbiota transplantation, with the potential for providing a biotherapeutic rationale for preventing injurious behaviors among individuals with mental disorders via restoring gut microbiota diversity and function.}, }
@article {pmid39199231, year = {2024}, author = {Mostafavi Abdolmaleky, H and Zhou, JR}, title = {Gut Microbiota Dysbiosis, Oxidative Stress, Inflammation, and Epigenetic Alterations in Metabolic Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {39199231}, issn = {2076-3921}, abstract = {Gut dysbiosis, resulting from an imbalance in the gut microbiome, can induce excessive production of reactive oxygen species (ROS), leading to inflammation, DNA damage, activation of the immune system, and epigenetic alterations of critical genes involved in the metabolic pathways. Gut dysbiosis-induced inflammation can also disrupt the gut barrier integrity and increase intestinal permeability, which allows gut-derived toxic products to enter the liver and systemic circulation, further triggering oxidative stress, inflammation, and epigenetic alterations associated with metabolic diseases. However, specific gut-derived metabolites, such as short-chain fatty acids (SCFAs), lactate, and vitamins, can modulate oxidative stress and the immune system through epigenetic mechanisms, thereby improving metabolic function. Gut microbiota and diet-induced metabolic diseases, such as obesity, insulin resistance, dyslipidemia, and hypertension, can transfer to the next generation, involving epigenetic mechanisms. In this review, we will introduce the key epigenetic alterations that, along with gut dysbiosis and ROS, are engaged in developing metabolic diseases. Finally, we will discuss potential therapeutic interventions such as dietary modifications, prebiotics, probiotics, postbiotics, and fecal microbiota transplantation, which may reduce oxidative stress and inflammation associated with metabolic syndrome by altering gut microbiota and epigenetic alterations. In summary, this review highlights the crucial role of gut microbiota dysbiosis, oxidative stress, and inflammation in the pathogenesis of metabolic diseases, with a particular focus on epigenetic alterations (including histone modifications, DNA methylomics, and RNA interference) and potential interventions that may prevent or improve metabolic diseases.}, }
@article {pmid39198444, year = {2024}, author = {Chang, D and Gupta, VK and Hur, B and Cobo-López, S and Cunningham, KY and Han, NS and Lee, I and Kronzer, VL and Teigen, LM and Karnatovskaia, LV and Longbrake, EE and Davis, JM and Nelson, H and Sung, J}, title = {Gut Microbiome Wellness Index 2 enhances health status prediction from gut microbiome taxonomic profiles.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {7447}, pmid = {39198444}, issn = {2041-1723}, support = {TL1 TR002493/TR/NCATS NIH HHS/United States ; UL1TR002377//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; UL1 TR002377/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/genetics ; Humans ; *Feces/microbiology ; *Health Status ; Metagenome ; Bacteria/classification/genetics/isolation &amp; purification ; Female ; }, abstract = {Recent advancements in translational gut microbiome research have revealed its crucial role in shaping predictive healthcare applications. Herein, we introduce the Gut Microbiome Wellness Index 2 (GMWI2), an enhanced version of our original GMWI prototype, designed as a standardized disease-agnostic health status indicator based on gut microbiome taxonomic profiles. Our analysis involves pooling existing 8069 stool shotgun metagenomes from 54 published studies across a global demographic landscape (spanning 26 countries and six continents) to identify gut taxonomic signals linked to disease presence or absence. GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence (i.e., outside the "reject option"). This performance exceeds that of the original GMWI model and traditional species-level α-diversity indices, indicating a more robust gut microbiome signature for differentiating between healthy and non-healthy phenotypes across multiple diseases. When assessed through inter-study validation and external validation cohorts, GMWI2 maintains an average accuracy of nearly 75%. Furthermore, by reevaluating previously published datasets, GMWI2 offers new insights into the effects of diet, antibiotic exposure, and fecal microbiota transplantation on gut health. Available as an open-source command-line tool, GMWI2 represents a timely, pivotal resource for evaluating health using an individual's unique gut microbial composition.}, }
@article {pmid39197710, year = {2024}, author = {Vashishth, S and Ambasta, RK and Kumar, P}, title = {Deciphering the microbial map and its implications in the therapeutics of neurodegenerative disorder.}, journal = {Ageing research reviews}, volume = {100}, number = {}, pages = {102466}, doi = {10.1016/j.arr.2024.102466}, pmid = {39197710}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; Animals ; *Brain-Gut Axis/physiology ; Probiotics/therapeutic use ; }, abstract = {Every facet of biological anthropology, including development, ageing, diseases, and even health maintenance, is influenced by gut microbiota's significant genetic and metabolic capabilities. With current advancements in sequencing technology and with new culture-independent approaches, researchers can surpass older correlative studies and develop mechanism-based studies on microbiome-host interactions. The microbiota-gut-brain axis (MGBA) regulates glial functioning, making it a possible target for the improvement of development and advancement of treatments for neurodegenerative diseases (NDDs). The gut-brain axis (GBA) is accountable for the reciprocal communication between the gastrointestinal and central nervous system, which plays an essential role in the regulation of physiological processes like controlling hunger, metabolism, and various gastrointestinal functions. Lately, studies have discovered the function of the gut microbiome for brain health-different microbiota through different pathways such as immunological, neurological and metabolic pathways. Additionally, we review the involvement of the neurotransmitters and the gut hormones related to gut microbiota. We also explore the MGBA in neurodegenerative disorders by focusing on metabolites. Further, targeting the blood-brain barrier (BBB), intestinal barrier, meninges, and peripheral immune system is investigated. Lastly, we discuss the therapeutics approach and evaluate the pre-clinical and clinical trial data regarding using prebiotics, probiotics, paraprobiotics, fecal microbiota transplantation, personalised medicine, and natural food bioactive in NDDs. A comprehensive study of the GBA will felicitate the creation of efficient therapeutic approaches for treating different NDDs.}, }
@article {pmid39197065, year = {2024}, author = {Xu, W and Liu, AX and Liu, KH and Zhang, S and Gong, ZH and Xiao, WJ}, title = {l-Theanine Alleviates Ulcerative Colitis by Regulating Colon Immunity via the Gut Microbiota in an MHC-II-Dependent Manner.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {36}, pages = {19852-19868}, doi = {10.1021/acs.jafc.4c04379}, pmid = {39197065}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Glutamates/pharmacology/administration &amp; dosage ; *Colitis, Ulcerative/immunology/drug therapy/microbiology ; *Mice, Inbred C57BL ; *Colon/immunology/microbiology/drug effects ; Male ; Humans ; Macrophages/immunology/drug effects ; Histocompatibility Antigens Class II/immunology/genetics ; Bacteria/classification/drug effects/genetics/isolation &amp; purification/immunology ; T-Lymphocytes/immunology/drug effects ; Feces/microbiology ; }, abstract = {Alterations to the gut microbiota are associated with ulcerative colitis (UC), whereas restoration of normobiosis can effectively alleviate UC. l-Theanine has been shown to reshape the gut microbiota and regulate gut immunity. To investigate the mechanisms by which l-theanine alleviates UC, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice. In this study, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice to explore the mechanism by which l-theanine alleviates UC. By reducing inflammation in the colon, we demonstrated that l-theanine alleviates symptoms of UC. Meanwhile, l-theanine can improve the abundance of microbiota related to short-chain fatty acid, bile acid, and tryptophan production. Single-cell sequencing results indicated that l-theanine-mediated suppression of UC was associated with immune cell changes, especially regarding macrophages and T and B cells, and validated the immune cell responses to the gut microbiota. Further, flow cytometry results showed that the ability of dendritic cells, macrophages, and monocytes to present microbiota antigens to colonic T cells in an MHC-II-dependent manner was reduced after treating normal mouse fecal donors with l-theanine. These results demonstrate that l-theanine modulates colon adaptive and innate immunity by regulating the gut microbiota in an MHC-II-dependent manner, thereby alleviating UC.}, }
@article {pmid39194379, year = {2024}, author = {Noguera-Fernández, N and Candela-González, J and Orenes-Piñero, E}, title = {Probiotics, Prebiotics, Fecal Microbiota Transplantation, and Dietary Patterns in Inflammatory Bowel Disease.}, journal = {Molecular nutrition &amp; food research}, volume = {68}, number = {18}, pages = {e2400429}, doi = {10.1002/mnfr.202400429}, pmid = {39194379}, issn = {1613-4133}, support = {//Instituto Murciano de Investigaciones Biosanitarias Pascual Parrilla/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Inflammatory Bowel Diseases/therapy/microbiology/diet therapy ; *Prebiotics ; *Probiotics/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/physiology ; Diet ; Quality of Life ; }, abstract = {SCOPE: Inflammatory bowel disease (IBD) is one of the most common chronic and debilitating functional bowel disorders affecting around 11% of the population across the world. IBD is associated with 3.6 million physician visits per year, being the most common reason visiting a gastroenterologist and the second most common reason to be absent from work, sharply increasing the health care costs.<br><br>METHODS AND RESULTS: Several treatments seem to be effective in IBD symptoms relief, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary patterns. Probiotics (living microorganisms that can be supplemented) can protect against pathogenic bacteria due to their antimicrobial qualities. Prebiotics (nondigestible food ingredients) promote the growth of beneficial microbial strains in the gut, giving a health benefit to the host. FMT is supposed to directly change the recipient's microbial composition when a transfer of gastrointestinal microbiota from a healthy donor is carried out. And finally, dietary patterns are in the spotlight, due to the presence of certain nutrients in the gastrointestinal tract affecting gastrointestinal motility, sensitivity, barrier function, and gut microbiota.<br><br>CONCLUSION: It is particularly important to know what treatment options are available and which are the most efficient in relieving IBD symptoms and improving IBD patient's quality of life.}, }
@article {pmid39194187, year = {2024}, author = {Wang, L and Xu, Y and Li, L and Yang, B and Zhao, D and Ye, C and Lin, Z and Cui, J and Liu, Y and Zhu, W and Li, N and Tian, H and Chen, Q}, title = {The impact of small intestinal bacterial overgrowth on the efficacy of fecal microbiota transplantation in patients with chronic constipation.}, journal = {mBio}, volume = {15}, number = {10}, pages = {e0202324}, pmid = {39194187}, issn = {2150-7511}, mesh = {Humans ; *Constipation/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; *Intestine, Small/microbiology ; *Gastrointestinal Microbiome ; *Feces/microbiology ; *RNA, Ribosomal, 16S/genetics ; Bacteria/classification/isolation &amp; purification/genetics ; Aged ; Chronic Disease ; Quality of Life ; Young Adult ; }, abstract = {UNLABELLED: To investigate the impact of Small Intestinal Bacterial Overgrowth (SIBO) on the efficacy of Fecal Microbiota Transplantation (FMT) in patients with chronic constipation, our research team included 218 patients with chronic constipation treated with FMT. Based on the results of the SIBO breath test, the patients were divided into two groups: the constipation with SIBO group (SIBO) and the constipation without SIBO group (non-SIBO). The efficacy of the two groups was evaluated using constipation-related scoring scales. At the same time, feces and small intestinal fluid samples were collected from both groups before and after FMT to compare the changes in the intestinal microbiota through 16S rRNA sequencing. In this study, it was found that the clinical efficacy of FMT in the SIBO group was superior to that in the non-SIBO group. After FMT treatment, both groups showed a significant increase in bowel frequency and improvement in stool characteristics. Abdominal symptoms, rectal symptoms, and defecation symptoms were significantly alleviated (P < 0.05), and patients' quality of life was significantly enhanced (P < 0.05). After FMT, except for the Constipation Assessment Scale scores, other scale scores showed significant differences between the two groups, the SIBO group scoring significantly better than the non-SIBO group (P < 0.05). After FMT, there were minor changes in the colonic microbiota but more substantial changes in the small intestinal microbiota. At baseline, the SIBO group had a higher abundance of Veillonella, and lower abundances of Escherichia-Shigella and Acinetobacter compared to the non-SIBO group. Chronic constipation patients with SIBO have a better response to FMT than those without SIBO.<br><br>IMPORTANCE: Existing studies have rarely considered the impact of the small intestine's microbial state on the efficacy of fecal microbiota transplantation (FMT), nor have they extensively explored the effect of the small intestine's microbial state on the recovery of colonic motility. Therefore, this study investigates the influence of small intestinal bacterial overgrowth (SIBO) on the efficacy of FMT in treating constipation, specifically the impact of the microbial state of the small intestine on the restoration of colonic homeostasis, and consequently on the recovery of colonic motility.}, }
@article {pmid39193826, year = {2024}, author = {Jelveh Moghaddam, E and Pourmand, G and Ahmadi Badi, S and Yarmohammadi, H and Soltanipur, M and Mahalleh, M and Rezaei, M and Mirhosseini, SM and Siadat, SD}, title = {Gut microbiota alterations in renal transplant recipients and the risk of urinary tract infection and delayed graft function: A preliminary prospective study.}, journal = {Urologia}, volume = {91}, number = {4}, pages = {781-787}, doi = {10.1177/03915603241276742}, pmid = {39193826}, issn = {1724-6075}, mesh = {Humans ; *Kidney Transplantation ; *Gastrointestinal Microbiome ; Prospective Studies ; Male ; Female ; Case-Control Studies ; *Urinary Tract Infections/microbiology ; Middle Aged ; Adult ; *Delayed Graft Function ; Postoperative Complications/microbiology ; Risk Factors ; Kidney Failure, Chronic/complications ; }, abstract = {BACKGROUND: The implication of gut microbiota in the gut-kidney axis affects the pathophysiology of chronic kidney disease (CKD). Gut microbiota composition changes during CKD. We aimed to determine the relative frequency of important gut microbiota members in end-stage renal disease (ERSD) patients before and after renal transplantation compared to healthy subjects.<br><br>METHODS: Fifteen kidney transplant patients and 10 healthy subjects were recruited in this case-control prospective study. Fecal samples were taken sequentially from all patients before kidney transplantation, 1&#x2009;week, and 1&#x2009;month after it. The relative frequency of Lactobacillus spp., Bifidobacterium spp., Akkermansia muciniphila, Bacteroides fragilis, Escherichia coli, and Faecalibacterium pruasnitzii were determined through quantitative PCR. The obtained data was statistically analyzed by Stata software (Stata Corporation, USA).<br><br>RESULTS: The mean log number of all bacteria was significantly higher in healthy individuals than kidney transplant recipients (p&#x2009;<&#x2009;0.001) except for Lactobacillus where the mean levels were almost identical in the two groups (p&#x2009;=&#x2009;0.67). Moreover, 20% (3) of patients developed a urinary tract infection. Besides, 2 (13.33%) patients were diagnosed with delayed graft function. There were no statistically significant differences regarding changing trends in bacteria log number of Akkermansia muciniphila (p&#x2009;=&#x2009;0.12), Bacteroid fragilis (p&#x2009;=&#x2009;0.75), Bifidobacterium (p&#x2009;=&#x2009;0.99), Escherichia coli (p&#x2009;=&#x2009;0.5), Faecalibacterium (p&#x2009;=&#x2009;0.98), and Lactobacilli (p&#x2009;=&#x2009;0.93) between patients with and without delayed graft function (DGF).<br><br>CONCLUSION: Gut microbiota composition in patients with ESRD was significantly different from those without it. However, the microbiota profile did not significantly differ in patients with and without DGF.}, }
@article {pmid39193000, year = {2024}, author = {Wu, Q and Yuan, LW and Yang, LC and Zhang, YW and Yao, HC and Peng, LX and Yao, BJ and Jiang, ZX}, title = {Role of gut microbiota in Crohn's disease pathogenesis: Insights from fecal microbiota transplantation in mouse model.}, journal = {World journal of gastroenterology}, volume = {30}, number = {31}, pages = {3689-3704}, pmid = {39193000}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/therapy/pathology/metabolism ; Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Disease Models, Animal ; Mice ; Female ; Male ; Adult ; Feces/microbiology ; Trinitrobenzenesulfonic Acid ; Colon/microbiology/pathology/immunology ; Fibrosis ; Mesentery ; Intestinal Mucosa/microbiology/pathology ; Middle Aged ; Mice, Inbred C57BL ; Case-Control Studies ; Young Adult ; Permeability ; Adipose Tissue ; Adipokines/metabolism ; }, abstract = {BACKGROUND: Inflammatory bowel disease, particularly Crohn's disease (CD), has been associated with alterations in mesenteric adipose tissue (MAT) and the phenomenon termed "creeping fat". Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD, with these tissues characterized by inflammation and fibrosis.<br><br>AIM: To evaluate the complex interplay among MAT, creeping fat, inflammation, and gut microbiota in CD.<br><br>METHODS: Intestinal tissue and MAT were collected from 12 patients with CD. Histological manifestations and protein expression levels were analyzed to determine lesion characteristics. Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice. The intestinal and mesenteric lesions in these mice, as well as their systemic inflammatory status, were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects.<br><br>RESULTS: Pathological examination of MAT showed significant differences between CD-affected and unaffected colons, including significant differences in gut microbiota structure. Fetal microbiota transplantation (FMT) from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD ameliorated CD symptoms, whereas FMT from CD patients into these mice exacerbated CD symptoms. Notably, FMT influenced intestinal permeability, barrier function, and levels of proinflammatory factors and adipokines. Furthermore, FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD.<br><br>CONCLUSION: Gut microbiota play a critical role in the histopathology of CD. Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.}, }
@article {pmid39192045, year = {2025}, author = {Nikdasti, A and Khodadadi, ES and Ferdosi, F and Dadgostar, E and Yahyazadeh, S and Heidari, P and Ehtiati, S and Vakili, O and Khatami, SH}, title = {Nutritional Strategies in Major Depression Disorder: From Ketogenic Diet to Modulation of the Microbiota-Gut-Brain Axis.}, journal = {Molecular neurobiology}, volume = {62}, number = {3}, pages = {2973-2994}, pmid = {39192045}, issn = {1559-1182}, mesh = {Humans ; *Diet, Ketogenic/methods ; *Depressive Disorder, Major/diet therapy/microbiology ; *Gastrointestinal Microbiome/physiology ; *Brain/metabolism ; Animals ; *Brain-Gut Axis/physiology ; }, abstract = {Major depressive disorder (MDD) is a leading cause of disability worldwide. While traditional pharmacological treatments are effective for many cases, a significant proportion of patients do not achieve full remission or experience side effects. Nutritional interventions hold promise as an alternative or adjunctive approach, especially for treatment-resistant depression. This review examines the potential role of nutrition in managing MDD through addressing biological deficits and modulating pathways relevant to its pathophysiology. Specifically, it explores the ketogenic diet and gut microbiome modulation through various methods, including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Numerous studies link dietary inadequacies to increased MDD risk and deficiencies in nutrients like omega-3 s, vitamins D and B, magnesium, and zinc. These deficiencies impact neurotransmitters, inflammation, and other biological factors in MDD. The gut-brain axis also regulates mood, stress response, and immunity, and disruptions are implicated in MDD. While medications aid acute symptoms, nutritional strategies may improve long-term outcomes by preventing relapse and promoting sustained remission. This comprehensive review aims to provide insights into nutrition's multifaceted relationship with MDD and its potential for developing more effective integrated treatment approaches.}, }
@article {pmid39191760, year = {2024}, author = {Hartikainen, AK and Jalanka, J and Lahtinen, P and Ponsero, AJ and Mertsalmi, T and Finnegan, L and Crispie, F and Cotter, PD and Arkkila, P and Satokari, R}, title = {Fecal microbiota transplantation influences microbiota without connection to symptom relief in irritable bowel syndrome patients.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {73}, pmid = {39191760}, issn = {2055-5008}, support = {316338//Academy of Finland (Suomen Akatemia)/ ; 323156//Academy of Finland (Suomen Akatemia)/ ; }, mesh = {*Irritable Bowel Syndrome/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; *RNA, Ribosomal, 16S/genetics ; Female ; Male ; Adult ; Treatment Outcome ; *Gastrointestinal Microbiome ; Middle Aged ; Feces/microbiology ; Metagenomics/methods ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {Imbalanced microbiota may contribute to the pathophysiology of irritable bowel syndrome (IBS), thus fecal microbiota transplantation (FMT) has been suggested as a potential treatment. Previous studies on the relationship between clinical improvement and microbiota after FMT have been inconclusive. In this study, we used 16S rRNA gene amplicon and shotgun metagenomics data from a randomized, placebo controlled FMT trial on 49 IBS patients to analyze changes after FMT in microbiota composition and its functional potential, and to identify connections between microbiota and patients' clinical outcome. As a result, we found that the successful modulation of microbiota composition and functional profiles by FMT from a healthy donor was not associated with the resolution of symptoms in IBS patients. Notably, a donor derived strain of Prevotella copri dominated the microbiota in those patients in the FMT group who had a low relative abundance of P. copri pre-FMT. The results highlight the multifactorial nature of IBS and the role of recipient's microbiota in the colonization of donor's strains.}, }
@article {pmid39189787, year = {2024}, author = {Arcay, R and Barceló-Nicolau, M and Suárez, L and Martín, L and Reigada, R and Höring, M and Liebisch, G and Garrido, C and Cabot, G and Vílchez, H and Cortés-Lara, S and González de Herrero, E and López-Causapé, C and Oliver, A and Barceló-Coblijn, G and Mena, A}, title = {Gut microbiome and plasma lipidome analysis reveals a specific impact of Clostridioides difficile infection on intestinal bacterial communities and sterol metabolism.}, journal = {mBio}, volume = {15}, number = {10}, pages = {e0134724}, pmid = {39189787}, issn = {2150-7511}, support = {co-PI of the SYN17/12//Health Research Institute of the Balearic Islands (IdISBa)/ ; JUNIOR18/02//Health Research Institute of the Balearic Islands (IdISBa)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology/blood/therapy ; *Sterols/metabolism/blood ; *Lipid Metabolism ; *Clostridioides difficile/metabolism ; Bacteria/classification/metabolism/isolation &amp; purification/genetics ; Male ; Lipidomics ; Female ; Middle Aged ; Aged ; Feces/microbiology ; Lipids/blood ; Adult ; Fecal Microbiota Transplantation ; }, abstract = {UNLABELLED: Clostridioides difficile infection (CDI) causes alterations in the intestinal microbiota, frequently associated with changes in the gut metabolism of bile acids and cholesterol. In addition to the impact on microbiome composition and given the metabolic changes occurring during CDI, our work focuses on the importance to know the effects at the local and systemic levels, both during the infection and its treatment, by paying particular attention to plasma lipid metabolism due to its relationship with CDI pathogenesis. Specific changes, characterized by a loss of microbial richness and diversity and related to a reduction in short-chain acid-producing bacteria and an increase in bile salt hydrolase-producing bacteria, were observed in the gut microbiota of CDI patients, especially in those suffering from recurrent CDI (RCDI). However, gut microbiota showed its ability to restore itself after treatment, resembling healthy individuals, in those patients treated by fecal microbiome transfer (FMT), in contrast with those treated with antibiotics, and displaying increased levels of Eubacterium coprostanoligenes, a cholesterol-reducing anaerobe. Interestingly, changes in plasma lipidome revealed a global depletion in circulating lipids in CDI, with the largest impact on cholesteryl esters. CDI patients also showed a specific and consistent decrease in the levels of lipid species containing linoleic acid-an essential fatty acid-which were only partially recovered after antibiotic treatment. Analysis of the plasma lipidome reflects CDI impact on the gut microbiota and its metabolism, evidencing changes in sterol and fatty acid metabolism that are possibly related to specific alterations observed in gut microbial communities of CDI patients.<br><br>IMPORTANCE: There is increasing evidence about the influence the changes in microbiota and its metabolism has on numerous diseases and infections such as Clostridioides difficile infection (CDI). The knowledge of these changes at local and systemic levels can help us manage this infection to avoid recurrences and apply the best therapies, such as fecal microbiota transfer (FMT). This study shows a better restoration of the gut in FMT-treated patients than in antibiotic-treated patients, resembling healthy controls and showing increased levels of cholesterol-reducing bacteria. Furthermore, it evidences the CDI impact on plasma lipidome. We observed in CDI patients a global depletion in circulating lipids, particularly cholesteryl esters, and a specific decrease in linoleic acid-containing lipids, an essential fatty acid. Our observations could impact CDI management because the lipid content was only partially recovered after treatment, suggesting that continued nutritional support, aiming to restore healthy lipid levels, could be essential for a full recovery.}, }
@article {pmid39189608, year = {2024}, author = {Tejada, JN and Walters, WA and Wang, Y and Kordahi, M and Chassaing, B and Pickard, J and Nunez, G and Ley, R and Gewirtz, AT}, title = {Prevention and cure of murine C. difficile infection by a Lachnospiraceae strain.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2392872}, pmid = {39189608}, issn = {1949-0984}, support = {R01 DK083890/DK/NIDDK NIH HHS/United States ; R01 DK095782/DK/NIDDK NIH HHS/United States ; R01 DK099071/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Clostridioides difficile/genetics/growth &amp; development/physiology/pathogenicity ; *Clostridium Infections/microbiology/prevention &amp; control ; *Gastrointestinal Microbiome/drug effects ; *Germ-Free Life ; *Clostridiales/genetics/growth &amp; development ; Mice, Inbred C57BL ; Disease Models, Animal ; Feces/microbiology ; Female ; Anti-Bacterial Agents/pharmacology ; }, abstract = {We sought to better understand how intestinal microbiota confer protection against Clostridioides difficile (C. difficile) infection (CDI). We utilized gnotobiotic altered Schaedler flora (ASF) mice, which lack the abnormalities of germfree (GF) mice as well as the complexity and heterogeneity of antibiotic-treated mice. Like GF mice, ASF mice were highly prone to rapid lethal CDI, without antibiotics, while very low infectious doses resulted in chronic CDI. Administering such chronic CDI mice an undefined preparation of Clostridia lowered C. difficile levels by several logs. Importantly, such resolution of CDI was associated with colonization of Lachnospiraceae. Fractionation of the Clostridia population to enrich for Lachnospiraceae led to the appreciation that its CDI-impeding property strongly associated with a specific Lachnospiraceae strain, namely uncultured bacteria and archaea (UBA) 3401. UBA3401 was recalcitrant to being propagated as a pure culture but could be maintained in ASF mice, wherein it comprised up to about 50% of the intestinal microbiota, which was sufficient to generate a high-quality genomic sequence of this bacterium. Sequence analysis and ex vivo study of UBA3401 indicated that it had the ability to secrete substance(s) that directly impeded C. difficile growth. Moreover, in vivo administration of UBA3401/ASF feces provided strong protection to C. difficile challenge. Thus, UBA3401 may contribute to and/or provide a means to study microbiota-mediated CDI resistance.}, }
@article {pmid39189041, year = {2024}, author = {Haussmann, AJ and McMahan, ZH and Volkmann, ER}, title = {Understanding the gastrointestinal microbiome in systemic sclerosis: methodological advancements and emerging research.}, journal = {Current opinion in rheumatology}, volume = {36}, number = {6}, pages = {401-409}, pmid = {39189041}, issn = {1531-6963}, support = {K23 HL150237/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Scleroderma, Systemic/microbiology ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Fecal Microbiota Transplantation/methods ; }, abstract = {PURPOSE OF REVIEW: This review highlights the role of the gastrointestinal (GI) microbiome in systemic sclerosis (SSc). We describe techniques for evaluating the GI microbiome in humans, and emerging research linking GI microbiome alterations (i.e., dysbiosis) and distinct SSc clinical manifestations. We also address the evolving treatment landscape targeting dysbiosis in SSc.<br><br>RECENT FINDINGS: Recent literature brings into focus the complex relationship between the GI microbiome and SSc pathogenesis. Advanced techniques (e.g., shotgun metagenomics, meta-transcriptomics) provide deeper insights into microbial taxonomy and active gene expression, exposing dysbiosis as a potential driver of SSc. New studies demonstrate that SSc patients who possess specific SSc clinical features, (e.g., interstitial lung disease), have unique GI microbiome profiles.<br><br>SUMMARY: Dysbiosis is associated with specific clinical features in patients with SSc. New tools for studying the GI microbiome have furthered our understanding of the relationship between dysbiosis and SSc complications. Therapeutic avenues such as dietary adjustments, probiotics, antibiotics, mindfulness practices, and fecal transplants offer potential for managing SSc and preventing its progression through GI microbiome modulation. By clarifying what is known about the relationship between the GI dysbiosis, GI dysfunction, and SSc, this review enhances our understanding of SSc pathogenesis and proposes targeted interventions.}, }
@article {pmid39188602, year = {2024}, author = {Soldera, J}, title = {Navigating treatment resistance: Janus kinase inhibitors for ulcerative colitis.}, journal = {World journal of clinical cases}, volume = {12}, number = {24}, pages = {5468-5472}, pmid = {39188602}, issn = {2307-8960}, abstract = {The management of refractory ulcerative colitis (UC) and acute severe UC (ASUC) is challenging due to the lack of standardized approaches in cases resistant to multiple treatments. In this editorial, I investigate the efficacy and safety of Janus kinase inhibitors, particularly upadacitinib and tofacitinib, in controlling severe and refractory disease. I highlight a notable case report by Xu et al, which explores the case of a patient with primary nonresponse to two classes of biologics and two fecal microbiota transplants who exhibited a remarkable response to upadacitinib. Furthermore, I discuss the use of tofacitinib in refractory UC and ASUC, either as monotherapy or in combination with biologics, which has shown promising response rates. Additionally, emerging evidence of upadacitinib efficacy in ASUC is presented. Overall, these cases emphasize the complex nature of managing refractory ASUC and the potential of small-molecule therapies to achieve remission. Further research is needed to refine treatment strategies for patients with treatment-resistant UC.}, }
@article {pmid39188104, year = {2024}, author = {Naik, A and Godbole, MS}, title = {Elucidating the Intricate Roles of Gut and Breast Microbiomes in Breast Cancer Metastasis to the Bone.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {7}, number = {8}, pages = {e70005}, pmid = {39188104}, issn = {2573-8348}, mesh = {Humans ; *Breast Neoplasms/pathology/microbiology/therapy ; Female ; *Gastrointestinal Microbiome ; *Bone Neoplasms/secondary/microbiology/therapy ; *Tumor Microenvironment/immunology ; Breast/pathology/microbiology ; Microbiota ; Animals ; }, abstract = {BACKGROUND: Breast cancer is the most predominant and heterogeneous cancer in women. Moreover, breast cancer has a high prevalence to metastasize to distant organs, such as the brain, lungs, and bones. Patients with breast cancer metastasis to the bones have poor overall and relapse-free survival. Moreover, treatment using chemotherapy and immunotherapy is ineffective in preventing or reducing cancer metastasis.<br><br>RECENT FINDINGS: Microorganisms residing in the gut and breast, termed as the resident microbiome, have a significant influence on the formation and progression of breast cancer. Recent studies have identified some microorganisms that induce breast cancer metastasis to the bone. These organisms utilize multiple mechanisms, including induction of epithelial-mesenchymal transition, steroid hormone metabolism, immune modification, bone remodeling, and secretion of microbial products that alter tumor microenvironment, and enhance propensity of breast cancer cells to metastasize. However, their involvement makes these microorganisms suitable as novel therapeutic targets. Thus, studies are underway to prevent and reduce breast cancer metastasis to distant organs, including the bone, using chemotherapeutic or immunotherapeutic drugs, along with probiotics, antibiotics or fecal microbiota transplantation.<br><br>CONCLUSIONS: The present review describes association of gut and breast microbiomes with bone metastases. We have elaborated on the mechanisms utilized by breast and gut microbiomes that induce breast cancer metastasis, especially to the bone. The review also highlights the current treatment options that may target both the microbiomes for preventing or reducing breast cancer metastases. Finally, we have specified the necessity of maintaining a diverse gut microbiome to prevent dysbiosis, which otherwise may induce breast carcinogenesis and metastasis especially to the bone. The review may facilitate more detailed investigations of the causal associations between these microbiomes and bone metastases. Moreover, the potential treatment options described in the review may promote discussions and research on the modes to improve survival of patients with breast cancer by targeting the gut and breast microbiomes.}, }
@article {pmid39187939, year = {2024}, author = {Wan, L and Wang, H and Liang, Y and Zhang, X and Yao, X and Zhu, G and Cai, J and Liu, G and Liu, X and Niu, Q and Li, S and Zhang, B and Gao, J and Wang, J and Shi, X and Hu, L and Liu, X and Zou, Z and Yang, G}, title = {Effect of oral faecal microbiota transplantation intervention for children with autism spectrum disorder: A randomised, double-blind, placebo-controlled trial.}, journal = {Clinical and translational medicine}, volume = {14}, number = {9}, pages = {e70006}, pmid = {39187939}, issn = {2001-1326}, support = {2023YFC2706405//National Key Research and Development Program of China/ ; 2022YFC2705301//National Key Research and Development Program of China/ ; 7222187//Beijing Natural Science Foundation/ ; qzx-2023-1//Seventh Medical Center of Chinese PLA General Hospital/ ; 22JSZ20//Seventh Medical Center of Chinese PLA General Hospital/ ; 82170302//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Autism Spectrum Disorder/therapy ; Double-Blind Method ; Child ; Male ; Female ; Treatment Outcome ; Child, Preschool ; Placebos ; }, }
@article {pmid39187483, year = {2024}, author = {Li, H and Du, Y and Cheng, K and Chen, Y and Wei, L and Pei, Y and Wang, X and Wang, L and Zhang, Y and Hu, X and Lu, Y and Zhu, X}, title = {Gut microbiota-derived indole-3-acetic acid suppresses high myopia progression by promoting type I collagen synthesis.}, journal = {Cell discovery}, volume = {10}, number = {1}, pages = {89}, pmid = {39187483}, issn = {2056-5968}, support = {82122017//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82271069//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81870642//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81470613//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81670835//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {High myopia (HM) is a leading cause of blindness worldwide with currently no effective interventions available. A major hurdle lies in its often isolated perception as a purely ocular morbidity, disregarding potential systemic implications. Recent evidence suggests the existence of a gut-eye axis; however, the role of gut microbiota in the pathogenesis of HM remains largely unexplored. Herein, we provide a potential crosstalk among HM's gut dysbiosis, microbial metabolites, and scleral remodeling. Utilizing 16S rRNA gene sequencing, we observed an altered gut microbiota profile in HM patients with a significant reduction in probiotic abundance compared with healthy controls. Subsequent targeted metabolic profiling revealed a notable decrease in plasma levels of the gut microbiota-derived metabolite indole-3-acetic acid (3-IAA) among HM patients, which is closely associated with the reduced probiotics, both negatively correlated with HM severity. Genetic analyses determined that gut microbiota are causally associated with myopia risk. Importantly, when mice subjected to HM modeling receive fecal microbiota transplantation from healthy donors, there is an increase in 3-IAA plasma levels and simultaneous retardation of HM progression along with better maintenance of collagen type I alpha 1 (COL1A1) expression in the sclera. Furthermore, 3-IAA gavage achieves similar effects. Mechanistic investigations confirm the transcriptional activation of COL1A1 by 3-IAA via promoting the enrichment of SP1 to its promoter. Together, our findings provide novel insights into the gut microbiota-eye axis in the pathogenesis of HM and propose new strategies for HM intervention by remodeling the gut microbiota and indole supplementation.}, }
@article {pmid39187454, year = {2024}, author = {Lu, M and Xie, L and Yin, S and Zhou, J and Yi, L and Ye, L}, title = {The Gut Microbial Lipid Metabolite 14(15)-EpETE Inhibits Substance P Release by Targeting GCG/PKA Signaling to Relieve Cisplatin-Induced Nausea and Vomiting in Rats.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {9}, pages = {1769-1777}, pmid = {39187454}, issn = {1738-8872}, mesh = {Animals ; *Cisplatin/adverse effects ; *Cyclic AMP-Dependent Protein Kinases/metabolism ; Rats ; *Signal Transduction/drug effects ; *Substance P/metabolism ; Female ; *Gastrointestinal Microbiome/drug effects ; *Vomiting/chemically induced/metabolism/drug therapy ; *Nausea/chemically induced/metabolism/drug therapy ; Feces/chemistry/microbiology ; Fecal Microbiota Transplantation ; Rats, Sprague-Dawley ; Ileum/metabolism ; Antineoplastic Agents/adverse effects ; Disease Models, Animal ; }, abstract = {Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect related to activation of substance P (SP). SP activation can result from dysregulation of the gut-brain axis, and also from activation of protein kinase A signaling (PKA) signaling. In this study, we connected these factors in an attempt to unveil the mechanisms underlying CINV and develop new therapeutic strategies. Female rats were injected with cisplatin (Cis) to induce pica. Fecal samples were collected before/after injection, and subjected to lipid metabolomics analysis. In another portion of pica rats, the PKA inhibitor KT5720 was applied to investigate the involvement of PKA signaling in CINV, while fecal microbiota transplantation (FMT) was implemented to verify the therapeutic effect of the lipid metabolite 14(15)-EpETE. Pica symptoms were recorded, followed by ileal histological examination. The targeting relationship between 14(15)-EpETE and glucagon was determined by bioinformatics. SP and glucagon/PKA signaling in rat ileum, serum, and/or brain substantia nigra were detected by immunohistochemistry, enzyme-linked immunosorbent assay, and/or western blot. The results showed a significantly lower level of 14(15)-EpETE in rat feces after Cis injection. KT5720 treatment alleviated Cis-induced pica symptoms, ileal injury, SP content increase in the ileum, serum, and brain substantia nigra, and ileal PKA activation in rats. The ileal level of glucagon was elevated by Cis in rats. FMT exerted an effect similar to that of KT5720 treatment, relieving the Cis-induced changes, including ileal glucagon/PKA activation in rats. Our findings demonstrate that FMT restores 14(15)-EpETE production, which inhibits SP release by targeting GCG/PKA signaling, ultimately mitigating CINV.}, }
@article {pmid39187187, year = {2024}, author = {Zhang, H and Wei, H and Qin, X and Song, H and Yang, M and Zhang, L and Liu, Y and Wang, Z and Zhang, Y and Lai, Y and Yang, J and Chen, Y and Chen, Z and Zeng, J and Wang, X and Liu, R}, title = {Is anxiety and depression transmissible? Depressed mother rats transmit anxiety- and depression-like phenotypes to cohabited rat pups through gut microbiota assimilation.}, journal = {Journal of affective disorders}, volume = {366}, number = {}, pages = {124-135}, doi = {10.1016/j.jad.2024.08.164}, pmid = {39187187}, issn = {1573-2517}, mesh = {Animals ; *Gastrointestinal Microbiome ; Rats ; *Anxiety/microbiology/psychology ; Female ; *Depression/microbiology/psychology ; *Fecal Microbiota Transplantation ; *Phenotype ; Male ; Mothers/psychology ; Behavior, Animal ; Disease Models, Animal ; Stress, Psychological/microbiology ; Rats, Sprague-Dawley ; }, abstract = {OBJECTIVE: This study is to investigate the role of gut microbiota transmission in the development of anxiety/depression in offspring exposed to maternal depression.<br><br>METHOD: Offspring rats were cohabitated with their depressed mother or father rats (which exposed to chronic unpredictable mild stress (CUMS)) for 2, 4, and 6&#xa0;months, the anxiety- and depression-like behaviors, and interaction/caring activities between mother/father and their pups were detected. The gut microbiota composition and its relationship with behaviors were analyzed. Fecal microbiota transplantation (FMT) was performed to establish the gut microbiota of depressed/normal mother rats in the offspring rats to further confirm the role of "depressive gut microbiota" transmission in mediating the anxiety/depression in the pups.<br><br>RESULTS: Anxiety and depression phenotypes can be transmitted from depressed mother rats to their cohabited offspring. Frequent interactions and gut microbiota assimilation were observed between rat mothers and their pups. Remodeling of the gut microbiota in pups by FMT could induce or attenuate anxiety- and depression-like phenotypes depending on the origin of the fecal microbiota. By comparison, the pups cohabiting with depressed father rats exhibited milder anxiety and depression.<br><br>CONCLUSIONS: These data together support that depressed mothers can transmit anxiety/depression to their pups through gut microbiota assimilation, which is related to frequent interactions. Our study reinforces the significance of mental health of mothers in preventing the occurrence of childhood anxiety and depression, and pointing out the possibility of remodeling intestinal microbiota as an effective therapeutic approach for treating anxiety/depression in children.}, }
@article {pmid39186389, year = {2024}, author = {Cotto, C and Baker, K and Fallon, E and Rimon, S}, title = {Fecal Microbiota, Live-jslm (RBL; REBYOTA ®) for Prevention of Recurrent Clostridioides difficile Infection: What Gastroenterology Nurses Need to Know.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {47}, number = {5}, pages = {378-382}, pmid = {39186389}, issn = {1538-9766}, mesh = {Humans ; *Clostridium Infections/prevention &amp; control ; *Clostridioides difficile ; *Fecal Microbiota Transplantation ; Gastroenterology ; Feces/microbiology ; Recurrence ; Secondary Prevention/methods ; }, }
@article {pmid39184689, year = {2024}, author = {Smith, B and Smith, H and Machini, M}, title = {Novel Pharmaceuticals and Therapeutics for Tumor Necrosis Factor-Alpha-Resistant Crohn's Disease: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e65357}, pmid = {39184689}, issn = {2168-8184}, abstract = {Inflammatory bowel disease (IBD) is a medical condition that causes persistent, relapsing inflammation of the gastrointestinal tract. It is an umbrella term encompassing two different conditions: ulcerative colitis (UC) and Crohn's disease (CD). The standard treatment for patients with moderate to severe CD is tumor necrosis factor-α (TNF-α) inhibitors; however, a subset of CD patients face challenges in regard to this disease's treatment. Certain populations of patients with CD may exhibit resistance or develop tolerance to TNF-α inhibitor therapy over time. The recurrent gastrointestinal inflammation associated with CD can severely impact the quality of life and lead to complications for those suffering from this condition. The symptomatic flare-ups these subpopulations continue to experience underscores why such a need for alternative therapies is desperately needed. These alternative therapies not only offer potential benefits for those with TNF-α resistance, but CD may also serve as a superior therapy option for those trying to avoid the adverse effects of CD treatments available today. This review aims to explore and investigate the novel drugs and therapies that are being investigated for the treatment of TNF-α resistant CD, such as upadacitinib, risankizumab, vedolizumab, synbiotics, fecal microbiota transplantation (FMT), and stem cell therapy. Upadacitinib is a Janus kinase inhibitor, Risankizumab is a monoclonal antibody targeting interleukin-23, and Vedolizumab is an integrin receptor antagonist. The latest advancements in CD management have shown encouraging results. Some of these novel drugs and therapies not only offer a potential solution for CD patients exhibiting resistance to TNF-α inhibitors but may also provide a superior alternative for individuals prone to opportunistic infections.}, }
@article {pmid39184030, year = {2024}, author = {Shera, S and Katzka, W and Yang, JC and Chang, C and Arias-Jayo, N and Lagishetty, V and Balioukova, A and Chen, Y and Dutson, E and Li, Z and Mayer, EA and Pisegna, JR and Sanmiguel, C and Pawar, S and Zhang, D and Leitman, M and Hernandez, L and Jacobs, JP and Dong, TS}, title = {Bariatric-induced microbiome changes alter MASLD development in association with changes in the innate immune system.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1407555}, pmid = {39184030}, issn = {1664-302X}, support = {UL1 TR000124/TR/NCATS NIH HHS/United States ; R01 DK048351/DK/NIDDK NIH HHS/United States ; P30 DK041301/DK/NIDDK NIH HHS/United States ; IK2 CX001717/CX/CSRD VA/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; }, abstract = {INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects nearly 25% of the population and is the leading cause for liver-related mortality. Bariatric surgery is a well-known treatment for MASLD and obesity. Understanding the fundamental mechanisms by which bariatric surgery can alter MASLD can lead to new avenues of therapy and research. Previous studies have identified the microbiome's role in bariatric surgery and in inflammatory immune cell populations. The host innate immune system modulates hepatic inflammation and fibrosis, and thus the progression of MASLD. The precise role of immune cell types in the pathogenesis of MASLD remains an active area of investigation. The aim of this study was to understand the interplay between microbiota composition post-bariatric surgery and the immune system in MASLD.<br><br>METHODS: Eighteen morbidly obese females undergoing sleeve gastrectomy were followed pre-and post-surgery. Stool from four patients, showing resolved MASLD post-surgery with sustained weight loss, was transplanted into antibiotic treated mice. Mice received pre-or post-surgery stool and were fed a standard or high-fat diet. Bodyweight, food intake, and physiological parameters were tracked weekly. Metabolic parameters were measured post-study termination.<br><br>RESULTS: The human study revealed that bariatric surgery led to significant weight loss (p&#x2009;>&#x2009;0.05), decreased inflammatory markers, and improved glucose levels six months post-surgery. Patients with weight loss of 20% or more showed distinct changes in blood metabolites and gut microbiome composition, notably an increase in Bacteroides. The mouse model confirmed surgery-induced microbiome changes to be a major factor in the reduction of markers and attenuation of MASLD progression. Mice receiving post-surgery fecal transplants had significantly less weight gain and liver steatosis compared to pre-surgery recipients. There was also a significant decrease in inflammatory cytokines interferon gamma, interleukin 2, interleukin 15, and mig. This was accompanied by alterations in liver immunophenotype, including an increase in natural killer T cells and reduction of Kupfer cells in the post-surgery transplant group.<br><br>DISCUSSION: Our findings suggest surgery induced microbial changes significantly reduce inflammatory markers and fatty liver progression. The results indicate a potential causal link between the microbiome and the host immune system, possibly mediated through modulation of liver NKT and Kupffer cells.}, }
@article {pmid39183943, year = {2024}, author = {Fitzjerrells, RL and Ollberding, NJ and Mangalam, AK}, title = {Looking at the full picture, using topic modeling to observe microbiome communities associated with disease.}, journal = {Gut microbes reports}, volume = {1}, number = {1}, pages = {1-11}, pmid = {39183943}, issn = {2993-3935}, support = {F31 DE033564/DE/NIDCR NIH HHS/United States ; I01 CX002212/CX/CSRD VA/United States ; R01 AI137075/AI/NIAID NIH HHS/United States ; T90 DE023520/DE/NIDCR NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; }, abstract = {The microbiome, a complex micro-ecosystem, helps the host with various vital physiological processes. Alterations of the microbiome (dysbiosis) have been linked with several diseases, and generally, differential abundance testing between the healthy and patient groups is performed to identify important bacteria. However, providing a singular species of bacteria to an individual as treatment has not been as successful as fecal microbiota transplant therapy, where the entire microbiome of a healthy individual is transferred. These observations suggest that a combination of bacteria might be crucial for the beneficial effects. Here we provide the framework to utilize topic modeling, an unsupervised machine learning approach, to identify a community of bacteria related to health or disease. Specifically, we used our previously published gut microbiome data of patients with multiple sclerosis (MS), a neurodegenerative disease linked to a dysbiotic gut microbiome. We identified communities of bacteria associated with MS, including genera previously discovered, but also others that would have been overlooked by differential abundance testing. This method can be a useful tool for analyzing the microbiome, and it should be considered along with the commonly utilized differential abundance tests to better understand the role of the gut microbiome in health and disease.}, }
@article {pmid39182245, year = {2024}, author = {Luo, X and Yang, X and Tan, S and Zhang, Y and Liu, Y and Tian, X and Huang, Y and Zhou, Y and He, C and Yin, K and Xu, D and Li, X and Sun, F and Tang, R and Cao, J and Zheng, K and Yu, Y and Pan, W}, title = {Gut microbiota mediates anxiety-like behaviors induced by chronic infection of Toxoplasma gondii in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2391535}, pmid = {39182245}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Anxiety/microbiology ; *Mice, Inbred C57BL ; *Toxoplasma/physiology ; Male ; Fecal Microbiota Transplantation ; Dysbiosis/microbiology ; Amygdala/metabolism ; Behavior, Animal ; Toxoplasmosis/physiopathology/psychology/parasitology/microbiology ; Chronic Disease ; Brain-Gut Axis/physiology ; Disease Models, Animal ; Colon/microbiology/parasitology ; }, abstract = {BACKGROUND: Chronic infection with the neurotropic parasite Toxoplasma gondii (T. gondii) can cause anxiety and gut microbiota dysbiosis in hosts. However, the potential role of gut microbiota in anxiety induced by the parasite remains unclear.<br><br>METHODS: C57BL/6J mice were infected with 10 cysts of T. gondii. Antibiotic depletion of gut microbiota and fecal microbiota transplantation experiments were utilized to investigate the causal relationship between gut microbiota and anxiety. Anxiety-like behaviors were examined by the elevated plus maze test and the open field test; blood, feces, colon and amygdala were collected to evaluate the profiles of serum endotoxin (Lipopolysaccharide, LPS) and serotonin (5-hydroxytryptamine, 5-HT), gut microbiota composition, metabolomics, global transcriptome and neuroinflammation in the amygdala. Furthermore, the effects of Diethyl butylmalonate (DBM, an inhibitor of mitochondrial succinate transporter, which causes the accumulation of endogenous succinate) on the disorders of the gut-brain axis were evaluated.<br><br>RESULTS: Here, we found that T. gondii chronic infection induced anxiety-like behaviors and disturbed the composition of the gut microbiota in mice. In the amygdala, T. gondii infection triggered the microglial activation and neuroinflammation. In the colon, T. gondii infection caused the intestinal dyshomeostasis including elevated colonic inflammation, enhanced bacterial endotoxin translocation to blood and compromised intestinal barrier. In the serum, T. gondii infection increased the LPS levels and decreased the 5-HT levels. Interestingly, antibiotics ablation of gut microbiota alleviated the anxiety-like behaviors induced by T. gondii infection. More importantly, transplantation of the fecal microbiota from T. gondii-infected mice resulted in anxiety and the transcriptomic alteration in the amygdala of the antibiotic-pretreated mice. Notably, the decreased abundance of succinate-producing bacteria and the decreased production of succinate were observed in the feces of the T. gondii-infected mice. Moreover, DBM administration ameliorated the anxiety and gut barrier impairment induced by T. gondii infection.<br><br>CONCLUSIONS: The present study uncovers a novel role of gut microbiota in mediating the anxiety-like behaviors induced by chronic T. gondii infection. Moreover, we show that DBM supplementation has a beneficial effect on anxiety. Overall, these findings provide new insights into the treatment of T. gondii-related mental disorders.}, }
@article {pmid39182099, year = {2024}, author = {Zheng, H and Zhang, X and Li, C and Wang, D and Shen, Y and Lu, J and Zhao, L and Li, X and Gao, H}, title = {BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {157}, pmid = {39182099}, issn = {2049-2618}, support = {22074106//National Natural Science Foundation of China/ ; 21974096//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Fibroblast Growth Factors/metabolism ; Mice ; *Gastrointestinal Microbiome ; *Diabetic Cardiomyopathies/metabolism/microbiology ; *Liver/metabolism ; *Amino Acids, Branched-Chain/metabolism ; Signal Transduction ; Diabetes Mellitus, Type 1/microbiology/metabolism ; Male ; Myocardium/metabolism/pathology ; PPAR alpha/metabolism ; Mice, Inbred C57BL ; Diabetes Mellitus, Experimental/metabolism/microbiology ; }, abstract = {BACKGROUND: Diabetic cardiomyopathy (DCM) is one of leading causes of diabetes-associated mortality. The gut microbiota-derived branched-chain amino acids (BCAA) have been reported to play a central role in the onset and progression of DCM, but the potential mechanisms remain elusive.<br><br>RESULTS: We found the type 1 diabetes (T1D) mice had higher circulating BCAA levels due to a reduced BCAA degradation ability of the gut microbiota. Excess BCAA decreased hepatic FGF21 production by inhibiting PPAR&#x3b1; signaling pathway and thereby resulted in a higher expression level of cardiac LAT1 via transcription factor Zbtb7c. High cardiac LAT1 increased the levels of BCAA in the heart and then caused mitochondrial damage and myocardial apoptosis through mTOR signaling pathway, leading to cardiac fibrosis and dysfunction in T1D mice. Additionally, transplant of faecal microbiota from healthy mice alleviated cardiac dysfunction in T1D mice, but this effect was abolished by FGF21 knockdown.<br><br>CONCLUSIONS: Our study sheds light on BCAA-mediated crosstalk among the gut microbiota, liver and heart to promote DCM and FGF21 serves as a key mediator. Video Abstract.}, }
@article {pmid39180723, year = {2024}, author = {Jiang, L and Hao, Y and Han, D and Dong, W and Yang, A and Sun, Z and Ge, Y and Duan, S and Zhang, X and Dai, Z}, title = {Gut microbiota dysbiosis deteriorates immunoregulatory effects of tryptophan via colonic indole and LBP/HTR2B-mediated macrophage function.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {39180723}, issn = {1751-7370}, support = {2022YFA1304204//National Key Research and Development Program of China/ ; 32072689//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dysbiosis/microbiology ; Mice ; *Colitis/chemically induced/immunology/microbiology ; *Tryptophan/metabolism ; *Indoles/pharmacology ; *Macrophages/immunology/drug effects ; *Mice, Inbred C57BL ; *Colon/microbiology/immunology ; *Disease Models, Animal ; *Carrier Proteins/genetics/metabolism ; *Dextran Sulfate ; Acute-Phase Proteins/metabolism ; Male ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/pharmacology ; Signal Transduction ; Membrane Glycoproteins ; }, abstract = {Tryptophan (Trp) has been shown to regulate immune function by modulating gut serotonin (5-HT) metabolism and signaling. However, the mechanisms underlying the microbial modulation of gut 5-HT signaling in gut inflammation with gut microbiota dysbiosis require further investigation. Here, we investigated the effects of Trp supplementation on the composition and metabolism of the gut microbiome and 5-HT signaling-related gut immune function using a dextran sodium sulfate (DSS)-induced colitis mouse model coupled with antibiotic exposure. The results showed that antibiotic treatment before but not during DSS treatment decreased the immunoregulatory effects of Trp and aggravated gut inflammation and body weight loss in mice. Metagenomic analysis revealed that the fecal microbiota transplantation of Trp-enriched gut microbiota to recipient mice subject to antibiotic pre-exposure and DSS treatment alleviated inflammation by increasing the relative abundances of Lactobacillus and Parabacteroides and the microbial production of indole coupled with the activation of the 5-HT receptor 2B (HTR2B) in the colon. Transcriptomic analysis showed that HTR2B agonist administration strengthened the beneficial effects of Trp in DSS-induced colitis mice with antibiotic exposure by reducing gut lipopolysaccharide-binding protein (LBP) production, IκB-α/nuclear factor-κB signaling, and M1 macrophage polarization. Indole treatment reduced LBP production and M1 macrophage polarization both in mice with DSS-induced colitis and in lipopolysaccharide-treated mouse macrophages; however, the HTR2B antagonist reversed the effects of indole. Our findings provide the basis for developing new dietary and therapeutic interventions to improve gut microbiota dysbiosis-associated inflammatory gut disorders and diseases.}, }
@article {pmid39180442, year = {2024}, author = {Wang, Z and Yang, L and Feng, Y and Duan, B and Zhang, H and Tang, Y and Zhang, C and Yang, J}, title = {Isoorientin Alleviates DSS-Treated Acute Colitis in Mice by Regulating Intestinal Epithelial P-Glycoprotein (P-gp) Expression.}, journal = {DNA and cell biology}, volume = {43}, number = {10}, pages = {520-536}, doi = {10.1089/dna.2024.0101}, pmid = {39180442}, issn = {1557-7430}, mesh = {Animals ; *Dextran Sulfate ; Mice ; *Colitis/chemically induced/metabolism/pathology ; *Gastrointestinal Microbiome/drug effects ; *Intestinal Mucosa/metabolism/drug effects ; *Luteolin/pharmacology ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism/genetics ; Mice, Inbred C57BL ; Male ; Fatty Acids, Volatile/metabolism ; Colon/metabolism/pathology/drug effects ; }, abstract = {Isoorientin (ISO) is a naturally occurring flavonoid with diverse functional properties that mitigate the risk of diseases stemming from oxidation, inflammation, and cancer cell proliferation. P-glycoprotein (P-gp) is a vital component of the intestinal epithelium and may play a role in the onset of intestinal inflammatory conditions, such as inflammatory bowel disease (IBD). Recent studies have suggested that short-chain fatty acids (SCFAs) and secondary bile acids (SBAs) produced by the gut microbiota stimulate the increase of P-gp expression, alleviating excessive inflammation and thereby preservation of intestinal homeostasis. ISO has been shown to improve colon health and modulate the gut microbiota. In this study, we aimed to explore whether ISO can modulate the microbes and their metabolites to influence P-gp expression to alleviate IBD. First, the impact of ISO on dextran sulfate sodium (DSS)-treated colitis in mice was investigated. Second, 16S rRNA gene sequencing was conducted. The present study indicated that ISO mitigated the symptoms and pathological damage associated with DSS-treated colitis in mice. Western blot analysis revealed ISO upregulated P-gp in colon tissues, suggesting the critical role of P-gp protein in intestinal epithelial cells. 16S microbial diversity sequencing revealed ISO restored the richness and variety of intestinal microorganisms in colitis-bearing mice and enriched SCFA-producing bacteria, such as Lachnospiraceae_NK4A136_group. The experiments also revealed that the ISO fecal microbiota transplantation (FMT) inoculation of DSS-treated mice had similarly beneficial results. FMT mice showed a reduction in colitis symptoms, which was more pronounced in ISO-FMT than in CON-FMT mice. Meanwhile, ISO-FMT expanded the abundance of beneficial microorganisms, increased the expression of metabolites, such as SCFAs and total SBAs, and significantly upregulated the expression of P-gp protein. In addition, Spearman's correlation analysis demonstrated a positive correlation between the production of SCFAs and SBAs and the expression of P-gp. The present study identified that ISO increases the expression of P-gp in the intestinal epithelium by regulating intestinal microorganisms and their metabolites, which maintains colonic homeostasis, improves the integrity of the colonic epithelium, and alleviates colitis.}, }
@article {pmid39180326, year = {2025}, author = {Feuerstadt, P and Chopra, T and Knapple, W and Van Hise, NW and Dubberke, ER and Baggott, B and Guthmueller, B and Bancke, L and Gamborg, M and Steiner, TS and Van Handel, D and Khanna, S}, title = {PUNCH CD3-OLS: A Phase 3 Prospective Observational Cohort Study to Evaluate the Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA) in Adults With Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {80}, number = {1}, pages = {43-51}, pmid = {39180326}, issn = {1537-6591}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; //Ferring Pharmaceuticals/ ; }, mesh = {Humans ; Male ; Female ; *Clostridium Infections/therapy/prevention &amp; control ; Middle Aged ; Prospective Studies ; Adult ; *Fecal Microbiota Transplantation/methods/adverse effects ; Aged ; Clostridioides difficile ; *Feces/microbiology ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use ; Canada ; United States ; Recurrence ; Young Adult ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA)-the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the US Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment.<br><br>METHODS: PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged &#x2265;18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24-72&#x2005;hours of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively.<br><br>RESULTS: Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups.<br><br>CONCLUSIONS: RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date, and findings support use of RBL to prevent rCDI in a broad patient population.<br><br>CLINICAL TRIALS REGISTRATION: NCT03931941.}, }
@article {pmid39180286, year = {2025}, author = {Jin, X and Sheng, W and Liu, X and Zhu, D}, title = {Optimizing Colonoscopy Preparation in Autistic Children: A Comparative Study of Hypertonic Sugar Saline and Normal Saline Enemas.}, journal = {Clinical pediatrics}, volume = {64}, number = {3}, pages = {368-372}, doi = {10.1177/00099228241275054}, pmid = {39180286}, issn = {1938-2707}, mesh = {Humans ; Male ; Female ; *Colonoscopy/methods ; *Enema/methods ; Retrospective Studies ; Child ; *Polyethylene Glycols/administration &amp; dosage ; Child, Preschool ; *Autistic Disorder/complications ; *Saline Solution/administration &amp; dosage ; Saline Solution, Hypertonic/administration &amp; dosage ; *Cathartics/administration &amp; dosage ; Administration, Oral ; }, abstract = {OBJECTIVE: This study evaluates the effectiveness of combining oral polyethylene glycol electrolyte solution with hypertonic sugar saline enema for colonoscopy preparation in autistic children.<br><br>METHODS: Clinical data of 58 children with autism who underwent fecal bacteria transplantation and transendoscopic enteral tubing (TET) catheterization at the hospital were retrospectively analyzed. Participants were allocated into 2 groups: a control group (26 children) and an observation group (32 children), differentiated by their intestinal preparation protocols. The control group was administered oral polyethylene glycol combined with normal saline enema, whereas the observation group was given oral polyethylene glycol combined with hypertonic sugar saline enema. The Boston Bowel Preparation Scale (BBPS) was used to score intestinal cleanliness. Differences in intestinal cleanliness and colonoscopy duration between the 2 groups were compared.<br><br>RESULTS: The group treated with hypertonic sugar saline enema exhibited significantly higher BBPS scores (6.78 &#xb1; 0.83) and an intestinal passage rate of 96.86%, which were statistically significant compared with the control group (P < 0.05). In addition, the colonoscopy duration was notably shorter in the observation group (14.03 &#xb1; 4.86 minutes) compared with the control group (P < 0.05).<br><br>CONCLUSION: Our findings suggest that an oral polyethylene glycol electrolyte solution combined with a hypertonic sugar saline enema is a more effective preparation method for colonoscopy in autistic children.}, }
@article {pmid39179176, year = {2024}, author = {Ngo, VL and Wang, Y and Wang, Y and Shi, Z and Britton, R and Zou, J and Ramani, S and Jiang, B and Gewirtz, AT}, title = {Select Gut Microbiota Impede Rotavirus Vaccine Efficacy.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {18}, number = {5}, pages = {101393}, pmid = {39179176}, issn = {2352-345X}, mesh = {Animals ; *Rotavirus Vaccines/immunology/administration &amp; dosage ; *Gastrointestinal Microbiome/immunology ; Humans ; Mice ; *Rotavirus Infections/prevention &amp; control/immunology/virology/microbiology ; *Vaccine Efficacy ; *Rotavirus/immunology ; *Fecal Microbiota Transplantation ; Female ; Antibodies, Viral/immunology/blood ; Vaccination ; Male ; Feces/microbiology/virology ; Child, Preschool ; Disease Models, Animal ; }, abstract = {BACKGROUND &amp; AIMS: The protection provided by rotavirus (RV) vaccines is highly heterogeneous among individuals. We hypothesized that microbiota composition might influence RV vaccine efficacy.<br><br>METHODS: First, we examined the potential of segmented filamentous bacteria (SFB) colonization to influence RV vaccine efficacy in mice. Next, we probed the influence of human microbiomes on RV vaccination via administering mice fecal microbial transplants (FMTs) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to RV vaccination followed by RV challenge.<br><br>RESULTS: SFB colonization induced a phenotype that was reminiscent of RV vaccine failure (ie, failure to generate RV antigens and, consequently, anti-RV antibodies following RV vaccination resulting in proneness to RV challenge after SFB levels diminished). FMTs from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMTs from high-responsive vaccinees copiously shed RV antigens and robustly generated anti-RV antibodies following RV vaccination. Concomitantly, such mice were impervious to RV challenge. In contrast, mice receiving FMTs from children who had not responded to RV vaccination exhibited only modest responses to RV vaccination and, concomitantly, remained prone to RV challenge. Microbiome analysis ruled out a role for SFB but suggested involvement of Clostridium perfringens. Oral administration of cultured C.&#xa0;perfringens to gnotobiotic mice partially recapitulated the RV vaccine non-responder phenotype. Analysis of published microbiome data found C.&#xa0;perfringens abundance in children modestly associated with RV vaccine failure.<br><br>CONCLUSION: Microbiota composition influences RV vaccine efficacy with C.&#xa0;perfringens being one, perhaps of many, potential contributing taxa.}, }
@article {pmid39178987, year = {2024}, author = {Shukla, V and Singh, S and Verma, S and Verma, S and Rizvi, AA and Abbas, M}, title = {Targeting the microbiome to improve human health with the approach of personalized medicine: Latest aspects and current updates.}, journal = {Clinical nutrition ESPEN}, volume = {63}, number = {}, pages = {813-820}, doi = {10.1016/j.clnesp.2024.08.005}, pmid = {39178987}, issn = {2405-4577}, mesh = {Humans ; *Precision Medicine ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Prebiotics ; *Dysbiosis/therapy ; Microbiota ; Synbiotics ; }, abstract = {The intricate ecosystem of microorganisms residing within and on the human body, collectively known as the microbiome, significantly influences human health. Imbalances in this microbiome, referred to as dysbiosis, have been associated with various diseases, prompting the exploration of novel therapeutic approaches. Personalized medicine, Tailors treatments to individual patient characteristics, offers a promising avenue for addressing microbiome-related health issues. This review highlights recent developments in utilizing personalized medicine to target the microbiome, aiming to enhance health outcomes. Noteworthy strategies include fecal microbiota transplantation (FMT), where healthy donor microbes are transferred to patients, showing promise in treating conditions such as recurrent Clostridium difficile infection. Additionally, probiotics, which are live microorganisms similar to beneficial gut inhabitants, and prebiotics, non-digestible compounds promoting microbial growth, are emerging as tools to restore microbiome balance. The integration of these approaches, known as synbiotics, enhances microbial colonization and therapeutic effects. Advances in metagenomics and sequencing technologies provide the means to understand individual microbiome profiles, enabling tailored interventions. This paper aims to present the latest insights in leveraging personalized medicine to address microbiome-related health concerns, envisioning a future where microbiome-based therapies reshape disease management and promote human health.}, }
@article {pmid39176325, year = {2024}, author = {Nilofar, F and Babu, N and Kumar, M and Palanisamy, S and T, G}, title = {From Hemorrhage to Diarrhea: The Comprehensive Clinical Journey of a Patient With Pseudomembranous Colitis.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e65176}, pmid = {39176325}, issn = {2168-8184}, abstract = {Pseudomembranous colitis (PC) is an inflammation of the colon primarily caused by the bacterium Clostridium difficile (C. difficile), often following antibiotic use. This case report describes the intricate clinical course of a 48-year-old male farmer with a history of chronic alcoholism, tobacco use, and seizure disorder, who presented with acute onset of left-sided weakness. CT brain revealed an intra-axial hemorrhage in the right gangliocapsular region with significant edema and midline shift. The patient's condition necessitated mechanical ventilation due to a low Glasgow Coma Scale (GCS) score. Complications ensued with the onset of ventilator-associated pneumonia (VAP) on day six, attributed to multi-drug resistant Acinetobacter baumannii, which was managed with meropenem and polymyxin. Following successful weaning from the ventilator, he experienced severe watery diarrhea, high-grade fever, and diffuse abdominal pain on day 13. Subsequent stool tests confirmed PC caused by C. difficile, characterized by diffuse colonic wall-thickening with a water target sign on contrast-enhanced CT (CECT) abdomen. Initial treatment with oral vancomycin and metronidazole was followed by symptomatic treatment. Two weeks later, the patient had a relapse of PC, presenting with multiple episodes of loose stools, which was managed with oral metronidazole alone. Colonoscopy and biopsy confirmed the relapse, showing inflamed colonic mucosa with pseudomembranes. This case highlights the importance of strict infection control, prudent antibiotic use, and close monitoring for these patients. It also suggests the potential role of fecal microbiota transplantation (FMT) for recurrent cases. The patient's recovery demonstrates the effectiveness of meticulous medical management and adherence to infection control protocols in achieving optimal outcomes.}, }
@article {pmid39173982, year = {2024}, author = {Ding, FF and Zhou, NN and Wang, T and Bao, MY and Qiao, F and Du, ZY and Zhang, ML}, title = {Fish gut-derived probiotic Pediococcus pentosaceus alleviates gossypol-induced intestinal inflammation by inhibiting NLRC3/NF-κB/IL-1β signal pathway in Nile tilapia.}, journal = {Fish &amp; shellfish immunology}, volume = {153}, number = {}, pages = {109852}, doi = {10.1016/j.fsi.2024.109852}, pmid = {39173982}, issn = {1095-9947}, mesh = {Animals ; *Cichlids/immunology ; *Fish Diseases/immunology/chemically induced/prevention &amp; control ; *Probiotics/pharmacology/administration &amp; dosage ; *Animal Feed/analysis ; *Pediococcus pentosaceus ; *Signal Transduction/drug effects ; *Gossypol/administration &amp; dosage/pharmacology ; Diet/veterinary ; Interleukin-1beta/genetics/metabolism ; Aeromonas hydrophila/physiology ; NF-kappa B/metabolism/genetics ; Gastrointestinal Microbiome/drug effects ; Intestines/drug effects/immunology ; Inflammation/veterinary/chemically induced/immunology ; Gram-Negative Bacterial Infections/veterinary/immunology ; Fish Proteins/genetics/metabolism/immunology ; Enteritis/veterinary/prevention &amp; control/chemically induced/immunology/microbiology ; }, abstract = {Cottonseed meal (CSM) and cottonseed protein concentrate (CPC) serve as protein alternatives to fish meal and soybean meal in the feed industry. However, the presence of gossypol residue in CSM and CPC can potentially trigger severe intestinal inflammation, thereby restricting the widespread utilization of these two protein sources. Probiotics are widely used to prevent or alleviate intestinal inflammation, but their efficacy in protecting fish against gossypol-induced enteritis remains uncertain. Here, the protective effect of Pediococcus pentosaceus, a strain isolated from the gut of Nile tilapia (Oreochromis niloticus), was evaluated. Three diets, control diet (CON), gossypol diet (GOS) and GOS supplemented with P. pentosaceus YC diet (GP), were used to feed Nile tilapia for 10 weeks. After the feeding trial, P. pentosaceus YC reduced the activity of myeloperoxidase (MPO) in the proximal intestine (PI) and distal intestine (DI). Following a 7-day exposure to Aeromonas hydrophila, the addition of P. pentosaceus YC was found to increase the survival rate of the fish. P. pentosaceus YC significantly inhibited the oxidative stress caused by gossypol, which was evidenced by lower reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in PI and DI. Addition of P. pentosaceus YC significantly inhibited enteritis, with the lower expression of pro-inflammatory cytokines (il-1β, il-6, il-8) and higher expression of anti-inflammatory cytokines tgf-β. RNA-seq analysis indicated that P. pentosaceus YC supplementation significantly inhibited nlrc3 and promoted nf-κb expression in PI and DI, and the siRNA interference experiment in vivo demonstrated that intestinal inflammation was mediated by NLRC3/NF-κB/IL-1β signaling pathway. Fecal bacteria transplantation experiment demonstrated that gut microbiota mediated the protective effect of P. pentosaceus YC. These findings offer valuable insights into the application of P. pentosaceus YC for alleviating gossypol-induced intestinal inflammation in fish.}, }
@article {pmid39173885, year = {2024}, author = {MacGibeny, MA and Adjei, S and Pyle, H and Bunick, CG and Ghannoum, M and Grada, A and Harris-Tryon, T and Tyring, SK and Kong, HH}, title = {Alterations in the Skin Microbiome in Dermatologic Diseases and with External Exposures: CME Part 2.}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, pmid = {39173885}, issn = {1097-6787}, support = {Z99 AR999999/ImNIH/Intramural NIH HHS/United States ; ZIA AR041219/ImNIH/Intramural NIH HHS/United States ; }, abstract = {In Part I of our CME we reviewed the skin microbiome in healthy individuals. Part II reviews the evolving understanding of alterations in the skin microbiome in specific human diseases. We also discuss how the skin microbiome can change with environmental exposures and medications such as antibiotics as well as ongoing research on microbiome-based interventions.}, }
@article {pmid39173756, year = {2024}, author = {Liu, J and Zhang, Z and Zhong, S and Zhang, X and Yang, J and Zhou, Q and Wang, D and Chang, X and Wang, H}, title = {Fecal microbiome transplantation alleviates manganese-induced neurotoxicity by altering the composition and function of the gut microbiota via the cGAS-STING/NLRP3 pathway.}, journal = {The Science of the total environment}, volume = {951}, number = {}, pages = {175681}, doi = {10.1016/j.scitotenv.2024.175681}, pmid = {39173756}, issn = {1879-1026}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology/drug effects ; *Fecal Microbiota Transplantation ; Mice ; *Mice, Inbred C57BL ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Membrane Proteins/metabolism ; Manganese/toxicity ; Neurotoxicity Syndromes ; Mice, Knockout ; Signal Transduction ; Nucleotidyltransferases ; }, abstract = {Manganese (Mn) is an environmental pollutant, and overexposure can cause neurodegenerative disorders similar to Alzheimer's disease and Parkinson's disease that are characterized by β-amyloid (Aβ) overexpression, Tau hyperphosphorylation and neuroinflammation. However, the mechanisms of Mn neurotoxicity are not clearly defined. In our study, a knockout mouse model of Mn exposure combined with gut flora-induced neurotoxicity was constructed to investigate the effect of gut flora on Mn neurotoxicity. The results showed that the levels of Tau, p-Tau and Aβ in the hippocampus of C57BL/6 mice were greater than those in the hippocampus of control mice after 5 weeks of continuous exposure to manganese chloride (Mn content of 200 mg/L). Transplanted normal and healthy fecal microbiota from mice significantly downregulated Tau, p-Tau and Aβ expression and ameliorated brain pathology. Moreover, Mn exposure activated the cGAS-STING pathway and altered the cecal microbiota profile, characterized by an increase in Clostridiales, Pseudoflavonifractor, Ligilactobacillus and Desulfovibrio, and a decrease in Anaerotruncus, Eubacterium_ruminantium_group, Fusimonas and Firmicutes, While fecal microbiome transplantation (FMT) treatment inhibited this pathway and restored the microbiota profile. FMT alleviated Mn exposure-induced neurotoxicity by inhibiting activation of the NLRP3 inflammasome triggered by overactivation of the cGAS-STING pathway. Deletion of the cGAS and STING genes and FMT altered the gut microbiota composition and its predictive function. Phenotypic prediction revealed that FMT markedly decreased the abundances of anaerobic and stress-tolerant bacteria and significantly increased the abundances of facultative anaerobic bacteria and biofilm-forming bacteria after blocking the cGAS-STING pathway compared to the Mn-exposed group. FMT from normal and healthy mice ameliorated the neurotoxicity of Mn exposure, possibly through alterations in the composition and function of the microbiome associated with the cGAS-STING/NLRP3 pathway. This study provides a prospective direction for future research on the mechanism of Mn neurotoxicity.}, }
@article {pmid39172643, year = {2024}, author = {Offersen, SM and Mao, X and Spiegelhauer, MR and Larsen, F and Li, VR and Sandris Nielsen, D and Aunsholt, L and Thymann, T and Brunse, A}, title = {Fecal virus-like particles are sufficient to reduce necrotizing enterocolitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2392876}, pmid = {39172643}, issn = {1949-0984}, mesh = {*Enterocolitis, Necrotizing/prevention &amp; control/therapy ; Animals ; *Feces/virology/microbiology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; Swine ; Humans ; Bacteria/classification/isolation &amp; purification/genetics ; Animals, Newborn ; Disease Models, Animal ; Virome ; Clostridium perfringens ; Bacteriophages/genetics/physiology ; Diarrhea/therapy/virology/prevention &amp; control/microbiology ; }, abstract = {Fecal filtrate transfer (FFT) is emerging as a safer alternative to traditional fecal microbiota transplantation (FMT) - particularly in the context of necrotizing enterocolitis (NEC), a severe gastrointestinal condition affecting preterm infants. Using a preterm piglet model, FFT has demonstrated superiority over FMT in safety and NEC prevention. Since FFT is virtually devoid of bacteria, prokaryotic viruses (bacteriophages) are assumed to mediate the beneficial effects. However, this assumption remains unproven. To address this gap, we separated virus-like particles (30 kDa to 0.45 µm) of donor feces from the residual postbiotic fluid. We then compared clinical and gut microbiota responses to these fractions with the parent FFT solution after transferring them to NEC-susceptible preterm piglets. Virome transfer was equally effective as FFT in reducing the severity of NEC-like pathology. The bacterial compositional data corroborated clinical findings as virome transfer reduced the relative abundance of several NEC-associated pathogens e.g. Klebsiella pneumoniae and Clostridium perfringens. Virome transfer diversified gut viral communities with concomitant constraining effects on the bacterial composition. Unexpectedly, virome transfer, but not residual postbiotic fluid, led to earlier diarrhea. While diarrhea may be a minor concern in human infants, future work should identify ways of eliminating this side effect without losing treatment efficacy.}, }
@article {pmid39172216, year = {2024}, author = {Xu, X and Jin, H and Li, X and Yan, C and Zhang, Q and Yu, X and Liu, Z and Liu, S and Zhu, F}, title = {Fecal Microbiota Transplantation Regulates Blood Pressure by Altering Gut Microbiota Composition and Intestinal Mucosal Barrier Function in Spontaneously Hypertensive Rats.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39172216}, issn = {1867-1314}, abstract = {Hypertension is accompanied by gut microbiota imbalance, but the role of bacteria in the pathogenesis of hypertension requires further study. In this study, we used fecal microbiota transplantation to determine the impact of microbiota composition on blood pressure in spontaneous hypertensive rats (SHRs), using normotensive Wistar Kyoto (WKY) rats as controls. SHRs were randomly divided into two groups (n = 10/group), SHR and SHR-T (SHR plus fecal transplantation) and WKY into WKY and WKY-T (WKY plus fecal transplantation). SHR-T received fecal transplantation from WKY, while WKY-T received fecal transplantation from SHR. Blood pressure was measured from the tail artery in conscious rats. 16S rDNA gene amplicon sequencing was used to analyze bacterial composition. Circulating levels of diamine oxidase, D-lactate, FITC-Dextrans, and lipopolysaccharide were determined. Hematoxylin and eosin (H&amp;E) staining was used to observe structural changes in the intestinal mucosa. Immunofluorescence, Western blot, and RT-PCR were utilized to determine changes in the expression of tight junction proteins. Following cross fecal transplantation, blood pressure decreased in SHR and increased in WKY. Significant differences in gut microbial composition were found between hypertensive and normotensive rats, specifically regarding the relative abundance of lactic and butyric acid-producing bacteria. Changes in gut microbiota composition also impacted the intestinal mucosal barrier integrity. Moreover, fecal transplantation affected the expression of tight junction proteins that may impact intestinal mucosal permeability and structural integrity. Blood pressure may be associated with butyric acid-producing intestinal microbiota and its function in regulating the integrity of intestinal mucosal barrier.}, }
@article {pmid39170992, year = {2024}, author = {Sanchez Cruz, C and Rojas Huerta, A and Lima Barrientos, J and Rodriguez, C and Devani, A and Boosahda, V and Rasagna Mareddy, NS and Briceno Silva, G and Del Castillo Miranda, JC and Reyes Gochi, KA and Reyes Gochi, MD and Alvarez, S and Ghattas Hasbun, PE}, title = {Inflammatory Bowel Disease and Cardiovascular Disease: An Integrative Review With a Focus on the Gut Microbiome.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e65136}, pmid = {39170992}, issn = {2168-8184}, abstract = {Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal tract. Recent research indicates a significant link between IBD and cardiovascular disease (CVD), the leading cause of global morbidity and mortality. This review examines the association between IBD and CVD, emphasizing the role of the gut microbiome in this relationship. IBD patients have a higher risk of cardiovascular events, such as coronary artery disease, heart failure, and cerebrovascular incidents, primarily due to chronic systemic inflammation, genetic factors, and gut microbiota imbalance (dysbiosis). Dysbiosis in IBD increases intestinal permeability, allowing bacterial products to enter the bloodstream, which promotes inflammation and endothelial dysfunction, contributing to CVD. Understanding the gut microbiome's role in IBD and CVD suggests new therapeutic interventions. Modulating the microbiome through diet, probiotics, and fecal microbiota transplantation (FMT) are promising research avenues. These interventions aim to restore a healthy gut microbiota balance, potentially reducing inflammation and improving cardiovascular outcomes. Additionally, the review emphasizes the importance of regular cardiovascular risk assessments and personalized preventive measures in managing IBD patients. Such measures include routine monitoring of cardiovascular health, tailored lifestyle modifications, and early intervention strategies to mitigate cardiovascular risk. By integrating current knowledge, this review aims to improve understanding and management of the interconnected pathophysiology of IBD and CVD. This approach will ultimately enhance patient outcomes and provide a foundation for future research and clinical practice guidelines in this area.}, }
@article {pmid39170985, year = {2024}, author = {Zou, X and Zou, X and Gao, L and Zhao, H}, title = {Gut microbiota and psoriasis: pathogenesis, targeted therapy, and future directions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1430586}, pmid = {39170985}, issn = {2235-2988}, mesh = {*Psoriasis/therapy/microbiology/drug therapy ; Humans ; *Gastrointestinal Microbiome ; *Medicine, Chinese Traditional ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Prebiotics ; Cytokines/metabolism ; Interleukin-17/metabolism ; }, abstract = {BACKGROUND: Psoriasis is one of the most common autoimmune skin diseases. Increasing evidence shows that alterations in the diversity and function of microbiota can participate in the pathogenesis of psoriasis through various pathways and mechanisms.<br><br>OBJECTIVE: To review the connection between microbial changes and psoriasis, how microbial-targeted therapy can be used to treat psoriasis, as well as the potential of prebiotics, probiotics, synbiotics, fecal microbiota transplantation, diet, and Traditional Chinese Medicine as supplementary and adjunctive therapies.<br><br>METHODS: Literature related to the relationship between psoriasis and gut microbiota was searched in PubMed and CNKI.<br><br>RESULTS: Adjunct therapies such as dietary interventions, traditional Chinese medicine, and probiotics can enhance gut microbiota abundance and diversity in patients with psoriasis. These therapies stimulate immune mediators including IL-23, IL-17, IL-22, and modulate gamma interferon (IFN-&#x3b3;) along with the NF-kB pathway, thereby suppressing the release of pro-inflammatory cytokines and ameliorating systemic inflammatory conditions.<br><br>CONCLUSION: This article discusses the direction of future research and clinical treatment of psoriasis from the perspective of intestinal microbiota and the mechanism of traditional Chinese medicine, so as to provide clinicians with more comprehensive diagnosis and treatment options and bring greater hope to patients with psoriasis.}, }
@article {pmid39166878, year = {2024}, author = {Lu, Q and Zhu, R and Zhou, L and Zhang, R and Li, Z and Xu, P and Wang, Z and Wu, G and Ren, J and Jiao, D and Song, Y and Li, J and Wang, W and Liang, R and Ma, X and Sun, Y}, title = {Gut dysbiosis contributes to the development of Budd-Chiari syndrome through immune imbalance.}, journal = {mSystems}, volume = {9}, number = {9}, pages = {e0079424}, pmid = {39166878}, issn = {2379-5077}, support = {81870457//MOST | National Natural Science Foundation of China (NSFC)/ ; 82172944//MOST | National Natural Science Foundation of China (NSFC)/ ; 81900558//MOST | National Natural Science Foundation of China (NSFC)/ ; 232102311048//Key science and technology project s of Henan Province/ ; }, mesh = {*Dysbiosis/microbiology/immunology ; *Gastrointestinal Microbiome/physiology ; *Budd-Chiari Syndrome/immunology/microbiology/pathology ; Humans ; Animals ; Mice ; Male ; Case-Control Studies ; Female ; *Cytokines/metabolism/immunology/genetics ; Adult ; Fecal Microbiota Transplantation ; Middle Aged ; }, abstract = {UNLABELLED: Budd-Chiari syndrome (B-CS) is a rare and lethal condition characterized by hepatic venous outflow tract blockage. Gut microbiota has been linked to numerous hepatic disorders, but its significance in B-CS pathogenesis is uncertain. First, we performed a case-control study (Ncase = 140, Ncontrol = 63) to compare the fecal microbiota of B-CS and healthy individuals by metagenomics sequencing. B-CS patients' gut microbial composition and activity changed significantly, with a different metagenomic makeup, increased potentially pathogenic bacteria, including Prevotella, and disease-linked microbial function. Imbalanced cytokines in patients were demonstrated to be associated with gut dysbiosis, which led us to suspect that B-CS is associated with gut microbiota and immune dysregulation. Next, 16S ribosomal DNA sequencing on fecal microbiota transplantation (FMT) mice models examined the link between gut dysbiosis and B-CS. FMT models showed damaged liver tissues, posterior inferior vena cava, and increased Prevotella in the disturbed gut microbiota of FMT mice. Notably, B-CS-FMT impaired the morphological structure of colonic tissues and increased intestinal permeability. Furthermore, a significant increase of the same cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, IL-17F, and IL-13) and endotoxin levels in B-CS-FMT mice were observed. Our study suggested that gut microbial dysbiosis may cause B-CS through immunological dysregulation.<br><br>IMPORTANCE: This study revealed that gut microbial dysbiosis may cause Budd-Chiari syndrome (B-CS). Gut dysbiosis enhanced intestinal permeability, and toxic metabolites and imbalanced cytokines activated the immune system. Consequently, the escalation of causative factors led to their concentration in the portal vein, thereby compromising both the liver parenchyma and outflow tract. Therefore, we proposed that gut microbial dysbiosis induced immune imbalance by chronic systemic inflammation, which contributed to the B-CS development. Furthermore, Prevotella may mediate inflammation development and immune imbalance, showing potential in B-CS pathogenesis.}, }
@article {pmid39166867, year = {2024}, author = {Sintes, R and McLellan, P and Navelli, G and Landman, C and Delage, S and Truong, S and Benech, N and Kapel, N and Moreino Sabater, A and Schnuriger, A and Eckert, C and Bleibtreu, A and Joly, A-C and Sokol, H}, title = {Use of frozen native feces for fecal microbiota transplantation in recurrent Clostridioides difficile infection: a simple way to improve the efficiency of donor feces preparation.}, journal = {Antimicrobial agents and chemotherapy}, volume = {68}, number = {10}, pages = {e0073424}, pmid = {39166867}, issn = {1098-6596}, support = {//Soci&#xe9;t&#xe9; Nationale Francaise de Gastro Enterologie/ ; //Soci&#xe9;t&#xe9; de Pathologie Infectieuse de Langue Francase/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Feces/microbiology ; *Clostridium Infections/therapy/microbiology ; *Clostridioides difficile ; Male ; Female ; Middle Aged ; Retrospective Studies ; Aged ; Adult ; Recurrence ; Freezing ; }, abstract = {Preparing fecal microbiota transplants immediately after donation is resource-intensive, and a proportion are destroyed following abnormal screening results. We retrospectively compared two processes, frozen fecal preparation (FFP) and fresh native frozen preparation (FNFP), for clinical efficacy in the treatment of recurrent Clostridioides difficile infection (rCDI). FFP and FNFP were similarly effective with clinical success rates of 76.7% and 86.7% (P = 0.32), respectively. FNFP is an efficient procedure that saves resources while maintaining clinical efficacy in rCDI.}, }
@article {pmid39165355, year = {2024}, author = {Huang, J and Zhang, J and Wang, F and Tang, X}, title = {Modified Gegen Qinlian Decoction modulated the gut microbiome and bile acid metabolism and restored the function of goblet cells in a mouse model of ulcerative colitis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1445838}, pmid = {39165355}, issn = {1664-3224}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/microbiology/drug therapy/metabolism/therapy ; Mice ; *Disease Models, Animal ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Goblet Cells/drug effects/metabolism ; *Bile Acids and Salts/metabolism ; Male ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Colon/pathology/metabolism/drug effects/microbiology ; }, abstract = {OBJECTIVE: Modified Gegen Qinlian Decoction (MGQD) has been shown to effectively relieve ulcerative colitis (UC) without a known pharmacological mechanism. In this study, the anti-colitis efficaciousness of MGQD and its underlying mechanisms in UC were evaluated.<br><br>METHODS: Mice with colitis were administered MGQD for 7 days. Following the evaluation of clinical symptoms, gut microbiota in the feces of UC mice was examined using 16S rRNA sequencing and bile acids (BAs) were examined using LC/MS. Gut microbiota consumption and fecal microbiota transplantation (FMT) were used to explore the involvement of gut microbiota in the anti-UC action of MGQD.<br><br>RESULTS: MGQD relieved colitis as shown by weight loss protection, a lower disease activity index (DAI), restoration of intestinal length reduction, and lower histopathologic scores. MGQD also restored crypt stem cell proliferation and function of colonic goblet cells, and promoted MUC2 protein secretion. Interestingly, investigations using gut bacterial depletion and FMT showed that MGQD attenuated colonic damage in a gut-dependent way. The modulation of the gut microbiota by MGQD might be attributed to a decrease in Odoribacter and an increase in norank_f_Muribaculaceae. In addition, MGQD modulated the metabolism of BAs while restoring the structure of the gut microbiota.<br><br>CONCLUSION: MGQD significantly alleviated colitis in mice, which may be associated with the modulation of gut microbiota and BA metabolism and restoration of function of goblet cells. However, factors other than the gut microbiota may also be involved in the amelioration of UC by MGQD.}, }
@article {pmid39163753, year = {2024}, author = {Wang, Z and Wang, X and Fu, L and Xu, S and Wang, X and Liao, Q and Zhuang, T and Liu, L and Zhang, H and Li, W and Xiong, A and Gu, L and Wang, Z and Wang, R and Tao, F and Yang, L and Ding, L}, title = {Shengmai San formula alleviates high-fat diet-induced obesity in mice through gut microbiota-derived bile acid promotion of M2 macrophage polarization and thermogenesis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {133}, number = {}, pages = {155938}, doi = {10.1016/j.phymed.2024.155938}, pmid = {39163753}, issn = {1618-095X}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome/drug effects ; *Obesity/drug therapy ; *Drugs, Chinese Herbal/pharmacology ; Male ; *Bile Acids and Salts/metabolism ; *Thermogenesis/drug effects ; *Mice, Inbred C57BL ; Mice ; *Macrophages/drug effects ; Adipose Tissue, White/drug effects ; Glucose Tolerance Test ; Disease Models, Animal ; }, abstract = {BACKGROUND: Shengmai San Formula (SMS) is a traditional Chinese medicine (TCM) that has been used to treat wasting-thirst regarded as diabetes mellitus, which occurs disproportionately in obese patients. Therefore, we investigated whether SMS could be used to treat obesity, and explored possible mechanisms by which it might improve glucose and fat metabolism.<br><br>METHODS: To investigate the effects of SMS on a high-fat diet (HFD)-induced obesity (DIO) model, we studied glucose metabolism via glucose tolerance testing (GTT) and insulin tolerance testing (ITT). Browning of white adipose tissue (WAT) was evaluated using H&amp;E staining, along with browning-related gene and protein expression. Changes in bile acid (BA) levels in serum, liver, ileum, and inguinal white adipose tissue were detected by Ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In addition, antimicrobial mixture (ABX) and fecal microbial transplantation (FMT) experiments were used to verify the role of gut flora in the effects produced by SMS on HFD-induced obesity model.<br><br>RESULTS: SMS ameliorated diet-induced dyslipidemia in a dose-dependent manner and reduced glucose intolerance and insulin resistance in DIO mice, helping to restore energy metabolism homeostasis. SMS significantly altered the structure of intestinal microbiome composition, decreasing the abundance of Lactobacillus carrying bile salt hydrolase (BSH) enzymes and thereby increasing the level of conjugated BAs in the blood, ileum, and iWAT. Increased TCA content promoted the secretion of Slit3 from M2 macrophages in iWAT, which activates the protein kinase A/calmodulin-dependent protein kinase II (PKA/CaMKII) signaling pathway in sympathetic neurons via the roundabouts receptor 1(ROBO1). This pathway promotes the synthesis and release of norepinephrine (NE), inducing cyclic adenosine monophosphate (cAMP) release in adipose tissue that activates the cyclic adenosine monophosphate/protein kinase A/phosphorylated hormone-sensitive lipase (cAMP/PKA/pHSL) pathway and enhances WAT browning. ABX treatment eliminated SMS effects on glucose and lipid metabolism in DIO mice, whereas glucose and lipid metabolism in obese mice improved following SMS-FMT and increased the level of serum bile acids.<br><br>CONCLUSION: SMS affects intestinal flora and bile acid composition in vivo and increased TCA promotes M2 macrophage polarization and Slit3 release in adipose tissue. This induces NE release and increases WAT browning in obese mice, which may be a mechanism by which SMS could be used to treat obesity.}, }
@article {pmid39163678, year = {2024}, author = {Wang, X and Peng, J and Cai, P and Xia, Y and Yi, C and Shang, A and Akanyibah, FA and Mao, F}, title = {The emerging role of the gut microbiota and its application in inflammatory bowel disease.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {179}, number = {}, pages = {117302}, doi = {10.1016/j.biopha.2024.117302}, pmid = {39163678}, issn = {1950-6007}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Inflammatory Bowel Diseases/microbiology/therapy ; *Dysbiosis/microbiology ; Animals ; *Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex disorder with an unknown cause. However, the dysbiosis of the gut microbiome has been found to play a role in IBD etiology, including exacerbated immune responses and defective intestinal barrier integrity. The gut microbiome can also be a potential biomarker for several diseases, including IBD. Currently, conventional treatments targeting pro-inflammatory cytokines and pathways in IBD-associated dysbiosis do not yield effective results. Other therapies that directly target the dysbiotic microbiome for effective outcomes are emerging. We review the role of the gut microbiome in health and IBD and its potential as a diagnostic, prognostic, and therapeutic target for IBD. This review also explores emerging therapeutic advancements that target gut microbiome-associated alterations in IBD, such as nanoparticle or encapsulation delivery, fecal microbiota transplantation, nutritional therapies, microbiome/probiotic engineering, phage therapy, mesenchymal stem cells (MSCs), gut proteins, and herbal formulas.}, }
@article {pmid39163526, year = {2024}, author = {van der Vossen, EWJ and Davids, M and Voermans, B and Wortelboer, K and Hartstra, AV and Koopen, AM and de Groot, P and Levin, E and Nieuwdorp, M}, title = {Disentangle beneficial effects of strain engraftment after fecal microbiota transplantation in subjects with MetSyn.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2388295}, pmid = {39163526}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; Male ; Middle Aged ; *Metabolic Syndrome/therapy/microbiology ; Female ; Feces/microbiology ; Bacteria/classification/isolation &amp; purification/metabolism/genetics ; Adult ; Blood Pressure ; Treatment Outcome ; }, abstract = {Fecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrome (MetSyn) receiving an FMT. We observed that a higher fraction of donor strains engrafted in the recipient is correlated to a reduction in diastolic blood pressure and found specific strain associations through canonical correlation analysis. Integrating the metabolomics profile shows that engraftment of Collinsella aerofaciens and Fusocatenibacter saccharovorans was related to a reduction in 2-oxoarginine in plasma, which was subsequently correlated to a reduction in diastolic blood pressure. In conclusion, we applied a novel framework to elucidate on the complex and heterogenous FMT intervention, establishing a connection between engrafted microbiota and clinical outcome parameters. Our findings underscore the potential therapeutic efficacy of FMT in ameliorating MetSyn, demonstrating a potential contribution of microbial strain engraftment to the improvement of MetSyn via modulation of circulating metabolites.}, }
@article {pmid39163273, year = {2024}, author = {Zhu, X and Dai, X and Zhao, L and Li, J and Zhu, Y and He, W and Guan, X and Wu, T and Liu, L and Song, H and Lei, L}, title = {Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2390136}, pmid = {39163273}, issn = {1949-0984}, mesh = {*Quercetin/pharmacology ; Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Energy Metabolism/drug effects ; *Metabolic Syndrome/metabolism/microbiology/drug therapy ; Male ; *Bile Acids and Salts/metabolism ; *Mice, Inbred C57BL ; *Thermogenesis/drug effects ; *Adipose Tissue, Brown/metabolism/drug effects ; Adipose Tissue, White/metabolism/drug effects ; Receptors, G-Protein-Coupled/metabolism/genetics ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.}, }
@article {pmid39163019, year = {2024}, author = {Manithody, C and Denton, C and Mehta, S and Carter, J and Kurashima, K and Bagwe, A and Swiderska-Syn, M and Guzman, M and Besmer, S and Jain, S and McHale, M and Qureshi, K and Nazzal, M and Caliskan, Y and Long, J and Lin, CJ and Hutchinson, C and Ericsson, AC and Jain, AK}, title = {Intraduodenal fecal microbiota transplantation ameliorates gut atrophy and cholestasis in a novel parenteral nutrition piglet model.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {327}, number = {5}, pages = {G640-G654}, pmid = {39163019}, issn = {1522-1547}, support = {NIH-1R03 DK121046-01//HHS | National Institutes of Health (NIH)/ ; NIH-P01AG078106-01//HHS | National Institutes of Health (NIH)/ ; R03 DK121046/DK/NIDDK NIH HHS/United States ; R21 AI169487/AI/NIAID NIH HHS/United States ; R01 DK131136/DK/NIDDK NIH HHS/United States ; NIH-1R01DK131136-01//HHS | National Institutes of Health (NIH)/ ; NIH-1U01 AI163064-01//HHS | National Institutes of Health (NIH)/ ; U01 AI163064/AI/NIAID NIH HHS/United States ; P01 AG078106/AG/NIA NIH HHS/United States ; NIH-R21AI169487-01//HHS | National Institutes of Health (NIH)/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Swine ; *Cholestasis/therapy/microbiology ; *Gastrointestinal Microbiome ; *Parenteral Nutrition, Total/methods ; Atrophy ; Disease Models, Animal ; Liver/pathology/metabolism ; }, abstract = {Total parenteral nutrition (TPN) provides lifesaving nutritional support intravenously; however, it is associated with significant side effects. Given gut microbial alterations noted with TPN, we hypothesized that transferring fecal microbiota from healthy controls would restore gut-systemic signaling in TPN and mitigate injury. Using our novel ambulatory model (US Patent: US 63/136,165), 31 piglets were randomly allocated to enteral nutrition (EN), TPN only, TPN + antibiotics (TPN-A), or TPN + intraduodenal fecal microbiota transplant (TPN + FMT) for 14 days. Gut, liver, and serum were assessed through histology, biochemistry, and qPCR. Stool samples underwent 16 s rRNA sequencing. Permutational multivariate analysis of variance, Jaccard, and Bray-Curtis metrics were performed. Significant bilirubin elevation in TPN and TPN-A versus EN (P < 0.0001) was prevented with FMT. IFN-G, TNF-α, IL-β, IL-8, and lipopolysaccharide (LPS) were significantly higher in TPN (P = 0.009, P = 0.001, P = 0.043, P = 0.011, P < 0.0001), with preservation upon FMT. Significant gut atrophy by villous-to-crypt ratio in TPN (P < 0.0001) and TPN-A (P = 0.0001) versus EN was prevented by FMT (P = 0.426 vs. EN). Microbiota profiles using principal coordinate analysis demonstrated significant FMT and EN overlap, with the largest separation in TPN-A followed by TPN, driven primarily by Firmicutes and Fusobacteria. TPN-altered gut barrier was preserved upon FMT; upregulated cholesterol 7 α-hydroxylase and bile salt export pump in TPN and TPN-A and downregulated fibroblast growth factor receptor 4, EGF, farnesoid X receptor, and Takeda G Protein-coupled Receptor 5 (TGR5) versus EN was prevented by FMT. This study provides novel evidence of prevention of gut atrophy, liver injury, and microbial dysbiosis with intraduodenal FMT, challenging current paradigms into TPN injury mechanisms and underscores the importance of gut microbes as prime targets for therapeutics and drug discovery.NEW &amp; NOTEWORTHY Intraduodenal fecal microbiota transplantation presents a novel strategy to mitigate complications associated with total parenteral nutrition (TPN), highlighting gut microbiota as a prime target for therapeutic and diagnostic approaches. These results from a highly translatable model provide hope for TPN side effect mitigation for thousands of chronically TPN-dependent patients.}, }
@article {pmid39162553, year = {2024}, author = {Yang, S and Tong, L and Li, X and Zhang, Y and Chen, H and Zhang, W and Zhang, H and Chen, Y and Chen, R}, title = {A novel clinically relevant human fecal microbial transplantation model in humanized mice.}, journal = {Microbiology spectrum}, volume = {12}, number = {10}, pages = {e0043624}, pmid = {39162553}, issn = {2165-0497}, support = {22KJA320005//Key University Science Research Project of Jiangsu Province ()/ ; KYCX23_2947//| Graduate Research and Innovation Projects of Jiangsu Province (Graduate Research and Innovation Project)/ ; }, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Humans ; *Fecal Microbiota Transplantation ; *Feces/microbiology ; *RNA, Ribosomal, 16S/genetics ; *Mice, Inbred C57BL ; *Bacteria/classification/genetics ; Female ; Bacteroidetes/genetics ; Male ; }, abstract = {The intact immune system of mice exhibits resistance to colonization by exogenous microorganisms, but the gut microbiota profiles of the humanized mice and the patterns of human fecal microbiota colonization remain unexplored. Humanized NCG (huNCG) mice were constructed by injected CD34 +stem cells. 16S rRNA sequencing and fecal microbiota transplantation (FMT) technologies were used to detect the differences in microbiota and selective colonization ability for exogenous community colonization among three mice cohorts (C57BL/6J, NCG, and huNCG). Flow cytometry analysis showed that all huNCG mice had over 25% hCD45 +in peripheral blood. 16S rRNA gene sequence analysis showed that compared with NCG mice, the gut microbiota of huNCG mice were significantly altered. After FMT, the principal coordinates analysis (PCoA) showed that the gut microbial composition of huNCG mice (huNCG-D9) was similar to that of donors. The relative abundance of Firmicutes and Bacteroidetes were significantly increased in huNCG mice compared to NCG mice. Further comparison of ASV sequences revealed that Bacteroides plebeius, Bacteroides finegoldii, Escherichia fergusonii, Escherichia albertii, Klebsiella pneumoniae, and Klebsiella variicola exhibited higher abundance and stability in huNCG mice after FMT. Furthermore, PICRUSt2 analysis showed that huNCG mice had significantly enhanced metabolism and immunity. This study demonstrated that humanized mice are more conducive to colonization within the human gut microbiota, which provides a good method for studying the association between human diseases and microbiota.IMPORTANCEThe gut microbiota and biomarkers of humanized mice are systematically revealed for the first time. The finding that human fecal microbiota colonize humanized mice more stably provides new insights into the study of interactions between immune responses and gut microbiota.}, }
@article {pmid39162211, year = {2024}, author = {Zhang, H and Xiao, Y and Wen, Q and Zhang, S and Li, P and Marcella, C and Hu, B and Liu, H and Zhang, F and Cui, B}, title = {Washed microbiota transplantation improved the level of serum vitamin D in ulcerative colitis.}, journal = {Journal of gastroenterology and hepatology}, volume = {39}, number = {11}, pages = {2394-2401}, doi = {10.1111/jgh.16717}, pmid = {39162211}, issn = {1440-1746}, support = {81600417//National Natural Science Foundation of China/ ; BK20211384//Natural Science Foundation of Jiangsu Province/ ; YKK23284//Nanjing Health Technology Development Project/ ; //Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; }, mesh = {Humans ; *Colitis, Ulcerative/therapy/blood/microbiology ; Male ; *Vitamin D/blood/analogs &amp; derivatives ; Female ; Adult ; *Fecal Microbiota Transplantation ; Middle Aged ; *Receptors, Calcitriol ; *Gastrointestinal Microbiome ; Vitamin D Deficiency/blood ; Treatment Outcome ; Mesalamine/therapeutic use ; }, abstract = {BACKGROUND AND AIM: Vitamin D (VD) deficiency was reported to correlate with ulcerative colitis (UC) activity, which might be closely related to gut microbiota dysbiosis. This study aims to investigate the effects of washed microbiota transplantation (WMT) on VD metabolism in UC.<br><br>METHODS: The serum levels of 25-hdroxyvitamin D [25(OH)D] in 121 patients with UC and 53 healthy controls (HC) were detected. Subsequently, a non-randomized control trial (non-RCT) was conducted. Patients with UC were non-randomly assigned to undergo WMT (n&#xa0;=&#xa0;28) vs. conventional treatment (5-aminosalicylic acid, 5-ASA, n&#xa0;=&#xa0;10). Serum levels of 25(OH)D, fecal microbiota, and the expression of vitamin D receptor (VDR) in patients with UC were evaluated with a 3-month follow-up.<br><br>RESULTS: Serum VD levels collected in the clinic practice indicated that patients with UC had significantly lower VD levels than HC (P&#xa0;<&#xa0;0.001). In the non-RCT, serum 25(OH)D level and VDR expression significantly increased (P&#xa0;=&#xa0;0.011, 0.026, respectively) in the WMT group, while no noticeable changes were observed in the non-WMT group. Microbiome profiling revealed that the increase in VD levels after WMT was positively associated with the abundances of Adlercreutzia_equolifaciens, Ruminococcus_obeum, and Dorea but negatively correlated with Escherichia.<br><br>CONCLUSIONS: The study suggested that WMT increases the levels of VD with characteristic changes of specific microbiota, which indicated the association between the VD and the activity of UC might be regulated by gut microbiota.}, }
@article {pmid39161885, year = {2024}, author = {Wang, J and Yuan, ZY and Wang, XY and Zhu, JX and Huang, WF and Xu, GH and Yi, LT}, title = {Anthocyanins-rich cranberry extract attenuates DSS-induced IBD in an intestinal flora independent manner.}, journal = {Current research in food science}, volume = {9}, number = {}, pages = {100815}, pmid = {39161885}, issn = {2665-9271}, abstract = {Cranberry is abundantly rich in anthocyanins, a type of flavonoid with potent antioxidant properties and the resistance against certain diseases. In this study, anthocyanin-rich cranberry extract was extracted, purified, and its components were analyzed. 92.18 % of anthocyanins was obtained and the total content of anthocyanins was 302.62 mg/g after AB-8 resin purification. Quantification analysis showed that the extract mainly contained cyanidin-3-galactoside, procyanidin B2 and procyanidin B4. Then we explored its effects on dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice. The supplementation of cranberry extract resulted in an alleviation of IBD symptoms, evidenced by improvements in the disease activity index (DAI), restoration of colon length and colonic morphology. Cranberry extract reversed the elevated iron and malondialdehyde (MDA) levels and restored glutathione (GSH) levels in IBD mice. Further analysis revealed that cranberry modulated ferroptosis-associated genes and reduced expression of pro-inflammatory cytokines. Although cranberry influenced the intestinal flora balance by reducing Proteobacteria and Escherichia-Shigella, and increasing Lactobacillus, as well as enhancing SCFAs content, these effects were not entirely dependent on intestinal flora modulation, as indicated by antibiotic intervention and fecal microbiota transplantation (FMT) experiments. In conclusion, our findings suggest that the beneficial impact of cranberry extract on IBD may primarily involve the regulation of colonic ferroptosis, independent of significant alterations in intestinal flora.}, }
@article {pmid39161797, year = {2024}, author = {Taha, AM and Abouelmagd, K and Nada, SA and Mahmoud, AM and Nguyen, D and Sharma, S and Elewa, M}, title = {Impact of fecal microbiota transplantation in severe alcoholic hepatitis: A systematic review and meta-analysis.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {8}, number = {8}, pages = {e70007}, pmid = {39161797}, issn = {2397-9070}, abstract = {BACKGROUND AND AIM: Severe alcoholic hepatitis (SAH) is a serious condition with few treatments. By modifying the gut-liver axis, fecal microbiota transplantation (FMT) was proposed as a treatment for SAH. The purpose of this meta-analysis was to evaluate the efficacy of FMT versus the standard of care (SOC) in improving SAH patient survival rates.<br><br>METHODS: A thorough search of electronic databases was conducted till September 2023. The survival rates of SAH patients undergoing FMT versus SOC were compared. Using Review Manager 5.4, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.<br><br>RESULTS: The meta-analysis consisted of six studies with a total of 371 patients with SAH. Patients who received FMT had significantly higher survival rates at 1 and 3&#x2009;months compared to those who received SOC, with pooled OR of 2.91 (95% CI: 1.56-5.42, P&#x2009;=&#x2009;0.0008) and 3.07 (95% CI: 1.81-5.20, P&#x2009;<&#x2009;0.0001), respectively. However, the survival advantage disappeared after 6&#x2009;months (OR: 2.96, 95% CI: 0.99-8.85, P&#x2009;=&#x2009;0.05) and 1 year of follow-up (OR: 1.81, 95% CI: 0.44-7.46, P&#x2009;=&#x2009;0.41).<br><br>CONCLUSION: This meta-analysis highlights the potential of FMT to significantly improve short-term survival rates in SAH patients. However, the survival benefit did not last 6-12&#x2009;months. These findings call for additional research into the effectiveness of FMT over the long term, along with strategies for extending the survival benefit.}, }
@article {pmid39161161, year = {2024}, author = {Yang, H and Shao, Y and Hu, Y and Qian, J and Wang, P and Tian, L and Ni, Y and Li, S and Al-Nusaif, M and Liu, C and Le, W}, title = {Fecal microbiota from patients with Parkinson's disease intensifies inflammation and neurodegeneration in A53T mice.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {30}, number = {8}, pages = {e70003}, pmid = {39161161}, issn = {1755-5949}, support = {YDZX20213100001002//Shanghai Municipal Central Government Funds for Guiding Local Scientific and Technological Development/ ; 32220103006//National Nature Science Foundation of China/ ; 82271524//National Nature Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Parkinson Disease/microbiology/metabolism ; Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Male ; Inflammation/metabolism/microbiology ; Feces/microbiology ; Mice, Transgenic ; Mice, Inbred C57BL ; Female ; alpha-Synuclein/metabolism ; Brain/metabolism/pathology ; }, abstract = {AIMS: We evaluated the potential of Parkinson's disease (PD) fecal microbiota transplantation to initiate or exacerbate PD pathologies and investigated the underlying mechanisms.<br><br>METHODS: We transplanted the fecal microbiota from PD patients into mice by oral gavage and assessed the motor and intestinal functions, as well as the inflammatory and pathological changes in the colon and brain. Furthermore, 16S rRNA gene sequencing combined with metabolomics analysis was conducted to assess the impacts of fecal delivery on the fecal microbiota and metabolism in recipient mice.<br><br>RESULTS: The fecal microbiota from PD patients increased intestinal inflammation, deteriorated intestinal barrier function, intensified microglia and astrocyte activation, abnormal deposition of &#x3b1;-Synuclein, and dopaminergic neuronal loss in the brains of A53T mice. A mechanistic study revealed that the fecal microbiota of PD patients stimulated the TLR4/NF-&#x3ba;B/NLRP3 pathway in both the brain and colon. Additionally, multiomics analysis found that transplantation of fecal microbiota from PD patients not only altered the composition of the gut microbiota but also influenced the fecal metabolic profile of the recipient mice.<br><br>CONCLUSION: The fecal microbiota from PD patients intensifies inflammation and neurodegeneration in A53T mice. Our findings demonstrate that imbalance and dysfunction in the gut microbiome play significant roles in the development and advancement of PD.}, }
@article {pmid39161102, year = {2024}, author = {Fasano, A and Chassaing, B and Haller, D and Flores Ventura, E and Carmen-Collado, M and Pastor, N and Koren, O and Berni Canani, R}, title = {Microbiota during pregnancy and early life: role in maternal-neonatal outcomes based on human evidence.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2392009}, pmid = {39161102}, issn = {1949-0984}, mesh = {Humans ; Pregnancy ; Female ; Infant, Newborn ; *Gastrointestinal Microbiome ; Milk, Human/microbiology ; Fecal Microbiota Transplantation ; Infant ; Host Microbial Interactions ; }, abstract = {Here, we explored the vast potential of microbiome-based interventions in preventing and managing non-communicable diseases including obesity, diabetes, allergies, celiac disease, inflammatory bowel diseases, malnutrition, and cardiovascular diseases across different life stages. We discuss the intricate relationship between microbiome and non-communicable diseases, emphasizing on the "window of opportunity" for microbe-host interactions during the first years after birth. Specific biotics and also live biotherapeutics including fecal microbiota transplantation emerge as pivotal tools for precision medicine, acknowledging the "one size doesn't' fit all" aspect. Challenges in implementation underscore the need for advanced technologies, scientific transparency, and public engagement. Future perspectives advocate for understanding maternal-neonatal microbiome, exploring the maternal exposome and delving into human milk's role in the establishment and restoration of the infant microbiome and its influence over health and disease. An integrated scientific approach, employing multi-omics and accounting for inter-individual variance in microbiome composition and function appears central to unleash the full potential of early-life microbiome interventions in revolutionizing healthcare.}, }
@article {pmid39159270, year = {2025}, author = {Romaní-Pérez, M and Líebana-García, R and Flor-Duro, A and Bonillo-Jiménez, D and Bullich-Vilarrubias, C and Olivares, M and Sanz, Y}, title = {Obesity and the gut microbiota: implications of neuroendocrine and immune signaling.}, journal = {The FEBS journal}, volume = {292}, number = {6}, pages = {1397-1420}, pmid = {39159270}, issn = {1742-4658}, support = {//The European Commission - NextGeneration EU/ ; CEX2021-001189-S//Spanish Ministry of Science and Innovation/ ; PID2020-119536RB-I00//Spanish Ministry of Science and Innovation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Obesity/microbiology/immunology/metabolism/pathology ; *Neurosecretory Systems/metabolism/immunology/microbiology ; Animals ; Signal Transduction ; Energy Metabolism ; }, abstract = {Obesity is a major health challenge due to its high prevalence and associated comorbidities. The excessive intake of a diet rich in fat and sugars leads to a persistent imbalance between energy intake and energy expenditure, which increases adiposity. Here, we provide an update on relevant diet-microbe-host interactions contributing to or protecting from obesity. In particular, we focus on how unhealthy diets shape the gut microbiota and thus impact crucial intestinal neuroendocrine and immune system functions. We describe how these interactions promote dysfunction in gut-to-brain neuroendocrine pathways involved in food intake control and postprandial metabolism and elevate the intestinal proinflammatory tone, promoting obesity and metabolic complications. In addition, we provide examples of how this knowledge may inspire microbiome-based interventions, such as fecal microbiota transplants, probiotics, and biotherapeutics, to effectively combat obesity-related disorders. We also discuss the current limitations and gaps in knowledge of gut microbiota research in obesity.}, }
@article {pmid39158846, year = {2025}, author = {Chen, J and Song, Y and Zeng, W and Wang, L and Qin, J and Fang, L and Ding, Y}, title = {RESEARCH PROGRESS ON THE ROLE OF GUT MICROBIOTA AND ITS METABOLITES IN THE OCCURRENCE AND DEVELOPMENT OF SEPTIC-ASSOCIATED LIVER INJURY.}, journal = {Shock (Augusta, Ga.)}, volume = {63}, number = {1}, pages = {4-10}, doi = {10.1097/SHK.0000000000002441}, pmid = {39158846}, issn = {1540-0514}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Sepsis/metabolism/microbiology ; Liver Diseases/microbiology/metabolism ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Sepsis is a life-threatening organ dysfunction that occurs due to a dysregulated host response to infection. Septic-associated liver injury (SALI) has been closely linked to the prognosis and mortality of sepsis. Recent investigations have delved into the gut-liver axis and its association with SALI, identifying its pivotal role in the gut microbiota. Bacterial translocation and the onset of SALI can occur due to an imbalance in the gut microbiota, impairing the function of the gut barrier. Moreover, their metabolites might exacerbate or initiate SALI by modulating immune responses. Nevertheless, interventions to restore the balance of the gut microbiota, such as the administration of probiotics, fecal microbiota transplantation, or dietary adjustments, may ameliorate SALI and enhance the prognosis and survival rates of septic patients. This review aimed to elucidate the function of the gut microbiota in the genesis and procession of SALI and its potential therapeutic value, offering a deeper understanding of the pathogenesis and therapeutic avenues for SALI.}, }
@article {pmid39158277, year = {2024}, author = {Cabirol, A and Chhun, A and Liberti, J and Kesner, L and Neuschwander, N and Schaerli, Y and Engel, P}, title = {Fecal transplant allows transmission of the gut microbiota in honey bees.}, journal = {mSphere}, volume = {9}, number = {9}, pages = {e0026224}, pmid = {39158277}, issn = {2379-5042}, support = {892574//EC | H2020 | PRIORITY 'Excellent science' | H2020 Marie Sk&#x142;odowska-Curie Actions (MSCA)/ ; 797113//EC | H2020 | PRIORITY 'Excellent science' | H2020 Marie Sk&#x142;odowska-Curie Actions (MSCA)/ ; 180575//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (SNF)/ ; 714804//EC | European Research Council (ERC)/ ; TMCG-3_213860//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (SNF)/ ; }, mesh = {Animals ; Bees/microbiology ; *Gastrointestinal Microbiome ; *RNA, Ribosomal, 16S/genetics ; *Feces/microbiology ; *Fecal Microbiota Transplantation ; *Bacteria/classification/isolation &amp; purification/genetics ; Host Microbial Interactions ; DNA, Bacterial/genetics ; Symbiosis ; }, abstract = {UNLABELLED: The study of the fecal microbiota is crucial for unraveling the pathways through which gut symbionts are acquired and transmitted. While stable gut microbial communities are essential for honey bee health, their modes of acquisition and transmission are yet to be confirmed. The gut of honey bees is colonized by symbiotic bacteria within 5 days after emergence from their wax cells as adults. Few studies have suggested that bees could be colonized in part via contact with fecal matter in the hive. However, the composition of the fecal microbiota is still unknown. It is particularly unclear whether all bacterial species can be found viable in the feces and can therefore be transmitted to newborn nestmates. Using 16S rRNA gene amplicon sequencing, we revealed that the composition of the honey bee fecal microbiota is strikingly similar to the microbiota of entire guts. We found that fecal transplantation resulted in gut microbial communities similar to those obtained from feeding gut homogenates. Our study shows that fecal sampling and transplantation are viable tools for the non-invasive analysis of bacterial community composition and host-microbe interactions. It also implies that contact of young bees with fecal matter in the hive is a plausible route for gut microbiota acquisition.<br><br>IMPORTANCE: Honey bees are crucial pollinators for many crops and wildflowers. They are also powerful models for studying microbiome-host interactions. However, current methods rely on gut tissue disruption to analyze microbiota composition and use gut homogenates to inoculate microbiota-deprived bees. Here, we provide two new and non-invasive approaches that will open doors to longitudinal studies: fecal sampling and transplantation. Furthermore, our findings provide insights into gut microbiota transmission in social insects by showing that ingestion of fecal matter can result in gut microbiota acquisition.}, }
@article {pmid39157730, year = {2024}, author = {Ceccon, M and Kantsjö, JB and Ronchi, F}, title = {Personalized Paths: Unlocking Alzheimer's via the Gut-Brain Axis.}, journal = {Visceral medicine}, volume = {40}, number = {4}, pages = {194-209}, pmid = {39157730}, issn = {2297-4725}, abstract = {BACKGROUND: Alzheimer's disease (AD) is characterised by abnormal protein aggregates in the brain that lead to cognitive decline. While current therapies only treat symptoms, disease-modifying treatments are urgently needed. Studies suggest that the composition of the microbiota is altered in people with AD, suggesting a link between gut bacteria and AD-related brain changes.<br><br>SUMMARY: In our narrative review, we explore various microbial interventions, such as faecal microbiota transplantation, probiotics, and diet, as powerful potential treatments. Studies suggest changes in microbiota composition following these interventions, with some beneficial effects on cognitive function. However, the mechanism of action of these microbial interventions is still unknown.<br><br>KEY MESSAGE: Our aim was to highlight the importance of personalised approaches, taking into account individual metabolic and microbiome profiles. We try to address gaps in current research and emphasise the need for microbiota analysis at different stages of the disease and its integration with clinical parameters and lifestyle information for a comprehensive understanding of AD progression (summarised in online suppl. Fig. 1; for all online suppl. material, see https://doi.org/10.1159/000535869).}, }
@article {pmid39155775, year = {2024}, author = {Jarasvaraparn, C and Rodrigo, M and Hartley, C and Karnsakul, W}, title = {Exploring odevixibat's efficacy in alagille syndrome: insights from recent clinical trials and IBAT inhibitor experiences.}, journal = {Expert opinion on pharmacotherapy}, volume = {25}, number = {12}, pages = {1647-1655}, doi = {10.1080/14656566.2024.2392873}, pmid = {39155775}, issn = {1744-7666}, mesh = {Humans ; *Alagille Syndrome/drug therapy ; *Bile Acids and Salts/metabolism ; Pruritus/drug therapy/etiology ; Animals ; Child ; Ileum/drug effects/metabolism ; Methylamines ; Thiazepines ; }, abstract = {INTRODUCTION: Alagille syndrome (ALGS) is a rare, genetic, multisystem disorder commonly associated with cholestatic liver disease; patients with ALGS may experience elevated serum bile acids and severe pruritus with associated impaired sleep. The ileal bile acid transporter (IBAT) is located on the luminal surface of enterocytes in the terminal ileum; this transport protein mediates resorption of conjugated bile acids for recirculation back to the liver. Inhibition of IBAT disrupts the enterohepatic circulation and leads to fecal elimination of bile acids.<br><br>AREAS COVERED: Here, the role of odevixibat as a novel, nonsurgical approach to interrupting the enterohepatic circulation from the intestine by inhibition of IBAT is reviewed, specifically in reference to currently available data on pharmacologic IBAT inhibition. IBAT inhibition has been shown to reduce serum bile acids and pruritus in trials of cholestatic liver diseases in children including ALGS.<br><br>EXPERT OPINION: Odevixibat or IBAT inhibitor should be considered as a first-line treatment for ALGS to improve pruritis, quality of life and liver-related outcomes including absence of liver transplant, surgical biliary diversion, hepatic decompensation, and death.}, }
@article {pmid39154362, year = {2024}, author = {Feng, R and Yang, W and Feng, W and Huang, X and Cen, M and Peng, G and Wu, W and Wang, Z and Jing, Y and Long, T and Liu, Y and Li, Z and Chang, G and Huang, K}, title = {Time-restricted feeding ameliorates non-alcoholic fatty liver disease through modulating hepatic nicotinamide metabolism via gut microbiota remodeling.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2390164}, pmid = {39154362}, issn = {1949-0984}, mesh = {Animals ; *Non-alcoholic Fatty Liver Disease/metabolism/microbiology ; *Gastrointestinal Microbiome ; Mice ; *Liver/metabolism ; *Diet, High-Fat/adverse effects ; Male ; *Niacinamide/metabolism ; *Mice, Inbred C57BL ; Disease Models, Animal ; Lipid Metabolism ; Aldehyde Oxidase/metabolism ; Lipogenesis ; Hepatocytes/metabolism ; Humans ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) has emerged as a global health concern, lacking specific therapeutic strategies. Time-restricted feeding (TRF) regimen demonstrated beneficial effects in NAFLD; however, the underlying mechanisms remain unclear. In this study, we established a NAFLD mouse model through a high-fat diet (HFD) and implemented the 16:8 TRF regimen for a duration of 6 weeks. We demonstrated that TRF remarkably alleviated hepatic steatosis in HFD mice. Of note, aldehyde oxidase 1 (AOX1), a key enzyme in hepatic nicotinamide (NAM) catabolism, exhibited apparent upregulation in response to HFD, leading to abnormal accumulation of N-Methyl-6-pyridone-3-carboxamide (N-Me-6-PY, also known as 2PY) and N-Methyl-4-pyridone-5-carboxamide (N-Me-4-PY, also known as 4PY), whereas it was almost restored by TRF. Both N-Me-6-PY and N-Me-4-PY promoted de novo lipogenesis and fatty acid uptake capacities in hepatocyte, and aggravated hepatic steatosis in mice either fed chow diet or HFD. In contrast, pharmacological inhibition of AOX1 was sufficient to ameliorate the hepatic steatosis and lipid metabolic dysregulation induced by HFD. Moreover, transplantation of fecal microbiota efficiently mimicked the modulatory effect of TRF on NAM metabolism, thus mitigating hepatic steatosis and lipid metabolic disturbance, suggesting a gut microbiota-dependent manner. In conclusion, our study reveals the intricate relationship between host NAM metabolic modification and gut microbiota remodeling during the amelioration of NAFLD by TRF, providing promising insights into the prevention and treatment of NAFLD.}, }
@article {pmid39153277, year = {2024}, author = {Huang, Y and Chen, H and Chen, J and Wu, Q and Zhang, W and Li, D and Lu, Y and Chen, Y}, title = {Yellow tea polysaccharides protect against non-alcoholic fatty liver disease via regulation of gut microbiota and bile acid metabolism in mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {133}, number = {}, pages = {155919}, doi = {10.1016/j.phymed.2024.155919}, pmid = {39153277}, issn = {1618-095X}, mesh = {Animals ; *Non-alcoholic Fatty Liver Disease/prevention &amp; control/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Bile Acids and Salts/metabolism ; *Polysaccharides/pharmacology ; Male ; *Mice, Inbred C57BL ; Mice ; *Tea/chemistry ; *Fecal Microbiota Transplantation ; Liver/drug effects/metabolism ; Prebiotics ; Fibroblast Growth Factors/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Amidohydrolases/metabolism ; }, abstract = {BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major clinical and global public health issue, with no specific pharmacological treatment available. Currently, there is a lack of approved drugs for the clinical treatment of NAFLD. Large-leaf yellow tea polysaccharides (YTP) is a natural biomacromolecule with excellent prebiotic properties and significant therapeutic effects on multiple metabolic diseases. However, the specific mechanisms by which YTP regulates NAFLD remain unclear.<br><br>PURPOSE: This study aims to explore the prebiotic effects of YTP and the potential mechanisms by which it inhibits hepatic cholesterol accumulation in NAFLD mice.<br><br>METHODS: The effects of YTP on lipid accumulation were evaluated in NAFLD mice through obesity trait analysis and bile acids (BAs) metabolism assessment. Additionally, fecal microbiota transplantation (FMT) was performed, and high-throughput sequencing was employed to investigate the mechanisms underlying YTP's regulatory effects on gut microbiota and BA metabolism.<br><br>RESULTS: Our study demonstrated that YTP altered the constitution of colonic BA, particularly increasing the levels of conjugated BA and non-12OH BA, which suppressed ileum FXR receptors and hepatic BA reabsorption, facilitated BA synthesis, and fecal BA excretion. The modifications were characterized by a decrease in the levels of FXR, FGF15, FGFR4, and ASBT proteins, and an increase in the levels of Cyp7a1 and Cyp27a1 proteins. YTP might affect enterohepatic circulation and by the activated the hepatic FXR-SHP pathway. Meanwhile, YTP reshaped the intestinal microbiome structure by decreasing BSH-producing genera and increasing taurine metabolism genera. The correlation analysis implied that Muribaculaceae, Pseudomonas, acterium_coprostanoligenes_group, Clostridiales, Lachnospiraceae_NK4A136_group, Delftia, Dubosiella, and Romboutsia were strongly correlated with specific BA monomers.<br><br>CONCLUSIONS: YTP modulates bile salt hydrolase-related microbial genera to activate alternative bile acid synthesis pathways, thereby inhibiting NAFLD progression. These results suggest that YTP may serve as a potential probiotic formulation, offering a feasible dietary intervention for NAFLD.}, }
@article {pmid39152200, year = {2024}, author = {Han, Z and Sun, J and Jiang, B and Chen, K and Ge, L and Sun, Z and Wang, A}, title = {Fecal microbiota transplantation accelerates restoration of florfenicol-disturbed intestinal microbiota in a fish model.}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {1006}, pmid = {39152200}, issn = {2399-3642}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Thiamphenicol/analogs &amp; derivatives/pharmacology ; *Fecal Microbiota Transplantation ; *Dysbiosis/therapy/microbiology ; *Anti-Bacterial Agents/pharmacology/adverse effects ; Carps/microbiology ; Bacteria/metabolism/drug effects ; }, abstract = {Antibiotic-induced dysbiosis in the fish gut causes significant adverse effects. We use fecal microbiota transplantation (FMT) to accelerate the restoration of florfenicol-perturbed intestinal microbiota in koi carp, identifying key bacterial populations and metabolites involved in the recovery process through microbiome and metabolome analyses. We demonstrate that florfenicol disrupts intestinal microbiota, reducing beneficial genera such as Lactobacillus, Bifidobacterium, Bacteroides, Romboutsia, and Faecalibacterium, and causing mucosal injuries. Key metabolites, including aromatic amino acids and glutathione-related compounds, are diminished. We show that FMT effectively restores microbial populations, repairs intestinal damage, and normalizes critical metabolites, while natural recovery is less effective. Spearman correlation analyses reveal strong associations between the identified bacterial genera and the levels of aromatic amino acids and glutathione-related metabolites. This study underscores the potential of FMT to counteract antibiotic-induced dysbiosis and maintain fish intestinal health. The restored microbiota and normalized metabolites provide a basis for developing personalized probiotic therapies for fish.}, }
@article {pmid39150086, year = {2024}, author = {Di Stefano, M}, title = {Fecal Microbiota Transplantation in the Treatment of Severe Constipation in Children: Is It the Future?.}, journal = {The American journal of gastroenterology}, volume = {119}, number = {11}, pages = {2187-2188}, doi = {10.14309/ajg.0000000000002985}, pmid = {39150086}, issn = {1572-0241}, }
@article {pmid39147234, year = {2024}, author = {Li, Z and Sun, T and He, Z and Li, Z and Xiong, J and Xiang, H}, title = {Intestinal Dysbacteriosis Contributes to Persistent Cognitive Impairment after Resolution of Acute Liver Failure.}, journal = {The American journal of pathology}, volume = {194}, number = {11}, pages = {2076-2090}, doi = {10.1016/j.ajpath.2024.07.014}, pmid = {39147234}, issn = {1525-2191}, mesh = {Animals ; *Liver Failure, Acute/complications/pathology/metabolism ; *Cognitive Dysfunction/microbiology/etiology/metabolism ; Mice ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/complications/microbiology ; Male ; *Hepatic Encephalopathy/pathology/microbiology ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Disease Models, Animal ; Brain/pathology/metabolism ; Synaptic Transmission/physiology ; Thioacetamide/toxicity ; }, abstract = {Regulating the gut microbiota alleviates hepatic encephalopathy (HE). Whether it is imperative to withhold treatment for microbial imbalance after liver functional recovery remains unclear. The aim of this work was to elucidate the alterations in cognitive behavior, liver function, synaptic transmission, and brain metabolites in acute liver failure (ALF) mice before and after hepatic function recovery. Towards this end, thioacetamide was injected intraperitoneally to establish an ALF mouse model, which induced HE. Hierarchical clustering analysis indicated that while the liver functions normalized, cognitive dysfunction and intestinal dysbacteriosis occurred in the ALF mice 14 days after thioacetamide injection. In addition, fecal microbiota transplantation from the ALF mice with liver function recovery induced liver injury and cognitive impairment. Alterations in synaptic transmission were found in the ALF mice with liver function improvement, and the correlations between the gut bacteria and synaptic transmission in the cortex were significant. Finally, apparent alterations in the brain metabolic profiles of the ALF mice were detected after liver function improvement by performing [1]H nuclear magnetic resonance spectroscopy, suggesting a risk of HE. These results showed that intestinal dysbacteriosis in ALF mice with liver function recovery is sufficient to induce liver injury and cognitive impairment. This indicates that continuous care may be necessary for monitoring microbial imbalance even in patients with ALF-induced HE whose liver function has recovered significantly.}, }
@article {pmid39146793, year = {2024}, author = {Sartor, RB}, title = {Microbiome modification for personalized treatment of dysbiotic diseases.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {8}, pages = {1219-1224}, doi = {10.1016/j.chom.2024.07.023}, pmid = {39146793}, issn = {1934-6069}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Dysbiosis/therapy ; *Precision Medicine/methods ; *Gastrointestinal Microbiome ; Clostridium Infections/therapy/microbiology ; Inflammation ; Clostridioides difficile ; Biomarkers ; }, abstract = {Fecal microbial transplantation (FMT) for inflammatory diseases or refractory immune checkpoint inhibitor therapy is less effective than for preventing recurrent Clostridioides difficile infection. This commentary outlines strategies to use biomarkers of successful FMT to guide newer approaches to restore microbial homeostasis in individuals with dysbiosis-mediated inflammation.}, }
@article {pmid39146792, year = {2024}, author = {Chambers, L and Grencewicz, D and Spakowicz, D}, title = {From poo to promise: Fecal microbiota transplants support immunotherapy re-sensitization in solid tumors.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {8}, pages = {1217-1218}, doi = {10.1016/j.chom.2024.07.015}, pmid = {39146792}, issn = {1934-6069}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use ; Gastrointestinal Microbiome/immunology ; Melanoma/therapy/immunology ; Neoplasms/therapy/immunology ; Esophageal Neoplasms/therapy/immunology/microbiology ; Carcinoma, Hepatocellular/therapy/immunology/microbiology ; Liver Neoplasms/therapy/immunology ; Animals ; Feces/microbiology ; }, abstract = {Fecal microbiota transplants (FMTs) recently entered the cancer therapeutics field as a method to resensitize treatment-resistant melanoma patients to immune checkpoint inhibitors (ICIs). In this issue of Cell Host &amp; Microbe, Kim and colleagues extend its utility to other solid tumors, including esophageal and hepatocellular carcinomas.[1].}, }
@article {pmid39141079, year = {2024}, author = {Suárez-Carantoña, C and Corbacho-Loarte, MD and Del Campo Albendea, L and Kamel-Rey, S and Halperin, AV and Escudero-Sánchez, R and Ponce-Alonso, M and Moreno, S and Cobo, J}, title = {Is advanced age still a risk factor for recurrence of C. difficile infection in the era of new treatments?.}, journal = {Age and ageing}, volume = {53}, number = {8}, pages = {}, doi = {10.1093/ageing/afae182}, pmid = {39141079}, issn = {1468-2834}, mesh = {Humans ; Male ; Aged, 80 and over ; *Clostridium Infections/epidemiology/mortality/microbiology/therapy/diagnosis/drug therapy ; Female ; Retrospective Studies ; Risk Factors ; *Recurrence ; Aged ; Age Factors ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; Middle Aged ; Fidaxomicin/therapeutic use ; Broadly Neutralizing Antibodies/therapeutic use ; Antibodies, Monoclonal ; }, abstract = {BACKGROUND: Advanced age has been widely identified as a risk factor for recurrent Clostridioides difficile infection (CDI), but most related studies were performed before the introduction of novel therapies. The aim of this study was to compare CDI characteristics and outcomes in patients over and under 80 years old with CDI and their outcomes in the era of new treatments.<br><br>METHODS: This was a retrospective cohort study of patients diagnosed with CDI from January 2021 to December 2022 in an academic hospital. We compared recurrence and mortality at 12&#xa0;weeks after the end of treatment. An extension of the Fine and Grey model adjusted for competing events was used to assess the effect of age on recurrence.<br><br>RESULTS: Four hundred seventy-six patients were considered to have CDI (320 in patients <80&#xa0;years and 156 in &#x2265;80&#xa0;years). CDI in older patients was more frequently healthcare-associated and was more severe. Although the Charlson index was almost identical between populations, comorbidities clearly differed. New treatments (bezlotoxumab, fidaxomicin and faecal microbiota transplantation) were more frequently used in older patients without statistical significance (41.3% vs. 33.4%, P&#xa0;=&#x2009;.053). There were 69 (14.5%) recurrences, with no differences by age group after adjusting for competing events. Mortality was greater in the oldest (35.3%) than in the youngest (13.1%); P&#xa0;<&#x2009;.001.<br><br>CONCLUSIONS: No differences in CDI recurrence rates were found between age groups. However, there was a high mortality rate in patients &#x2265;80&#xa0;years old, which emphasises the urgent need to improve the prevention and treatment of CDI in this group.}, }
@article {pmid39141021, year = {2025}, author = {Mirzababaei, M and Babaei, F and Ghafghazi, S and Rahimi, Z and Asadi, S and Dargahi, L and Nassiri-Asl, M and Haghnazari, L}, title = {Saccharomyces Boulardii alleviates neuroinflammation and oxidative stress in PTZ-kindled seizure rat model.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {398}, number = {2}, pages = {1625-1635}, pmid = {39141021}, issn = {1432-1912}, support = {50000886//Kermanshah University of Medical Sciences/ ; }, mesh = {Animals ; *Oxidative Stress/drug effects ; Male ; Rats, Wistar ; Pentylenetetrazole ; *Seizures/chemically induced/metabolism/drug therapy ; *Probiotics/pharmacology/administration &amp; dosage ; *Saccharomyces boulardii ; Brain-Derived Neurotrophic Factor/metabolism ; Disease Models, Animal ; Rats ; Hippocampus/metabolism/drug effects ; Matrix Metalloproteinase 9/metabolism ; *Neuroinflammatory Diseases/metabolism/chemically induced ; Kindling, Neurologic/drug effects ; Behavior, Animal/drug effects ; Cytokines/metabolism ; }, abstract = {Previous research have reported that modulating the gut microbiome composition by fecal microbiota transplantation and probiotic administration can alleviate seizure occurrence and severity. Saccharomyces boulardii (SB) is a yeast probiotic that has demonstrated ameliorating effects on anxiety, memory and cognitive deficit, and brain amyloidogenesis. In this research, our goal was to examine the anti-seizure effects of SB on the pentylenetetrazole (PTZ)-kindled male Wistar rats. The animals were randomly categorized into four test groups. The rats were orally administered with saline (control and PTZ groups) or S. boulardii (SB + PTZ and SB groups) for 57 days. From the 29th day of the experiment, the animals received intraperitoneally saline (control and SB groups) or PTZ (PTZ and SB + PTZ groups) on alternate days for 30 days. The administration dose of SB and PTZ was 10[10] CFU/ml/day and 35 mg/kg, respectively. We assessed animal seizure behavior, neuroinflammation, oxidative stress, and the levels of matrix metalloproteinase-9 (MMP-9) and brain-derived neurotrophic factor (BDNF) in the hippocampus tissue. S. boulardii hindered the PTZ-induced kindling development. SB treatment elevated glutathione (GSH) and total antioxidant capacity (TAC) and reduced malondialdehyde (MDA) levels. SB also lessened the hippocampal levels of BDNF and MMP-9. Following SB supplementation, proinflammatory cytokines interleukin-1 beta (IL-1β) and IL-6 were lowered, and anti-inflammatory cytokine IL-10 was enhanced. Overall, our data indicated, for the first time, the positive impact of SB on the PTZ-kindled seizure rat model. The anti-seizure activity of SB was mediated by modulating oxidative stress, neuroinflammation, and MMP-9 and BDNF levels.}, }
@article {pmid39140343, year = {2024}, author = {Wang, R and Huang, G and Li, S and Huang, H and Zhu, G and Wang, L and Yang, J and Yang, S and Jiang, Z and Zhang, W}, title = {Blueberry extract for the treatment of ischaemic stroke through regulating the gut microbiota and kynurenine metabolism.}, journal = {Phytotherapy research : PTR}, volume = {38}, number = {9}, pages = {4792-4814}, doi = {10.1002/ptr.8300}, pmid = {39140343}, issn = {1099-1573}, support = {0001/2023/AKP//Science and Technology Development Fund, Macau SAR/ ; 006/2023/SKL//Science and Technology Development Fund, Macau SAR/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; Rats ; *Kynurenine/metabolism ; *Blueberry Plants/chemistry ; Male ; *Plant Extracts/pharmacology ; *Ischemic Stroke/drug therapy/metabolism ; *Rats, Sprague-Dawley ; Humans ; Fecal Microbiota Transplantation ; Prevotella ; RNA, Ribosomal, 16S ; }, abstract = {Although the gut microbiota and kynurenine (KYN) metabolism have significant protective effects against ischaemic stroke (IS), the exact mechanism has yet to be fully elucidated. Combined serum metabolomics and 16S rRNA gene sequencing were used to reveal the differences between the gut microbiota and metabolites in rats treated with or without blueberry extract. Faecal microbiota transplantation (FMT) was employed to validate the protective role of the gut microbiota in IS. Furthermore, the interaction between Prevotella and IS was also confirmed in patients. Rats with IS experienced neurological impairments accompanied by an impaired intestinal barrier and disturbed intestinal flora, which further contributed to heightened inflammatory responses. Furthermore, Prevotella played a critical role in IS pathophysiology, and a positive correlation between Prevotella and KYN was detected. The role of KYN metabolism in IS was further demonstrated by the finding that IDO was significantly upregulated and that the use of the IDO inhibitor, attenuated KYN metabolic pathway activity and ameliorated neurological damage in rats with IS. Prevotella intervention also significantly improved stroke symptoms and decreasing KYN levels in rats with IS. FMT showed that the beneficial effects of blueberry extract on IS involve gut bacteria, especially Prevotella, which were confirmed by microbiological analyses conducted on IS patients. Moreover, blueberry extract led to significant changes in kynurenic acid levels and tryptophan and IDO levels through interactions with Prevotella. Our study demonstrates for the first time that blueberry extract could modulate "intestinal microecology-KYN metabolism" to improve IS.}, }
@article {pmid39139438, year = {2024}, author = {Jing, L and Zhang, H and Xiang, Q and Hu, H and Zhai, C and Xu, S and Tian, H}, title = {Role of Trimethylamine N-Oxide in Heart Failure.}, journal = {Reviews in cardiovascular medicine}, volume = {25}, number = {7}, pages = {240}, pmid = {39139438}, issn = {2153-8174}, abstract = {Heart failure (HF) is a clinical syndrome characterizing by typical physical signs and symptomatology resulting from reduced cardiac output and/or intracardiac pressure at rest or under stress due to structural and/or functional abnormalities of the heart. HF is often the final stage of all cardiovascular diseases and a significant risk factor for sudden cardiac arrest, death, and liver or kidney failure. Current pharmacological treatments can only slow the progression and recurrence of HF. With advancing research into the gut microbiome and its metabolites, one such trimethylamine N-oxide (TMAO)-has been implicated in the advancement of HF and is correlated with poor prognosis in patients with HF. However, the precise role of TMAO in HF has not yet been clarified. This review highlights and concludes the available evidence and potential mechanisms associated with HF, with the hope of contributing new insights into the diagnosis and prevention of HF.}, }
@article {pmid39138075, year = {2024}, author = {Yeom, M and Ahn, S and Hahm, DH and Jang, SY and Jang, SH and Park, SY and Jang, JH and Park, J and Oh, JY and Lee, IS and Kim, K and Kwon, SK and Park, HJ}, title = {Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice.}, journal = {Journal of integrative medicine}, volume = {22}, number = {5}, pages = {600-613}, doi = {10.1016/j.joim.2024.07.004}, pmid = {39138075}, issn = {2095-4964}, mesh = {Animals ; *Dermatitis, Atopic/therapy/microbiology ; *Gastrointestinal Microbiome ; Mice ; *Acupuncture Therapy/methods ; Male ; Permeability ; Intestinal Mucosa/metabolism/microbiology ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome. Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events, but its underlying mechanism is not completely understood. The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent.<br><br>METHODS: AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse. Acupuncture was done at the Gok-Ji (LI11) acupoints. AD-like symptoms were assessed by lesion scores, scratching behavior, and histopathological changes; intestinal barrier function was measured by fecal output, serum lipopolysaccharide levels, histopathological changes, and mRNA expression of markers involved in intestinal permeability and inflammation. Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples.<br><br>RESULTS: Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening, and also significantly altered gut microbiota structure as revealed by &#x3b2;-diversity indices and analysis of similarities. These beneficial effects were eliminated by antibiotic depletion of gut microbiota, but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice. Interestingly, AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability, atrophy of the mucosal structure (reduced villus height and crypt depth), decreased expression of tight junctions and mucus synthesis genes, and increased expression of inflammatory mediators in the ileum. Acupuncture attenuated these abnormalities, which was gut microbiota-dependent.<br><br>CONCLUSION: Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier, providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD. Please cite this article as: Yeom M, Ahn S, Hahm DH, Jang SY, Jang SH, Park SY, Jang JH, Park J, Oh JY, Lee IS, Kim K, Kwon SK, Park HJ. Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice. J Integr Med. 2024; 22(5): 600-613.}, }
@article {pmid39137736, year = {2024}, author = {Cui, S and Huang, Q and Li, T and Shen, W and Chen, X and Sun, X}, title = {Reduction in Renal Interstitial Fibrosis in Aged Male Mice by Intestinal Microbiota Rejuvenation.}, journal = {Gerontology}, volume = {70}, number = {11}, pages = {1161-1170}, doi = {10.1159/000540839}, pmid = {39137736}, issn = {1423-0003}, mesh = {Animals ; Male ; *Gastrointestinal Microbiome ; *Fibrosis ; Mice ; *Aging/physiology ; *Fecal Microbiota Transplantation/methods ; *Kidney/pathology ; Cytokines/metabolism ; Signal Transduction ; Mice, Inbred C57BL ; Rejuvenation/physiology ; Kidney Diseases/therapy/pathology/microbiology/metabolism ; Tumor Suppressor Protein p53/metabolism ; Disease Models, Animal ; }, abstract = {INTRODUCTION: Renal interstitial fibrosis is an important pathological basis for kidney ageing and the progression of ageing nephropathy. In the present research, we established an aged mouse model of faecal microbiota transplantation (FMT), identified the rejuvenation features of the kidney in aged male mice, and preliminarily analysed the possible mechanism by which the rejuvenation of the intestinal microbiota reduces renal interstitial fibrosis and delays senescence in aged male mice.<br><br>METHODS: We established an aged male mice model that was treated with FMT (FMT-Old) and a normal aged male mice control group (Old). Differentially expressed cytokines were identified using a cytokine array, and changes in protein expression related to signal transduction pathways in renal tissues were detected using a signalling pathway array. Senescence-associated &#x3b2;-galactosidase and Masson staining were performed to observe the degrees of renal senescence and tubule interstitial fibrosis. Immunohistochemistry was utilized to detect changes in the expression of the ageing markers p53 and p21 and the inflammation-related protein nuclear factor (NF-&#x3ba;B) subunit (RelA/p65).<br><br>RESULTS: The pathological features of renal senescence in the FMT-Old group were significantly alleviated, and the levels of the ageing indicators p53 and p21 were decreased (p < 0.05). Ingenuity Pathway Analysis revealed that six differentially expressed cytokines, MIP-3&#x3b2; (CCL-19), E-selectin (SELE), Fas ligand (Fas L/FASLG), CXCL-11 (I-TAC), CXCL-1 and CCL-3 (MIP-1&#x3b1;) were related to a common upstream regulatory protein, RelA/p65, and the expression of this protein was significantly different between groups according to the signalling pathway array.<br><br>CONCLUSION: Our findings suggest that the intestinal microbiota regulates the renal microenvironment by reducing immune inflammatory responses through the inhibition of the NF-&#x3ba;B signalling pathway, thereby delaying renal senescence in aged male mice.}, }
@article {pmid39135690, year = {2024}, author = {Li, J and Wang, SY and Yan, KX and Wang, P and Jiao, J and Wang, YD and Chen, ML and Dong, Y and Zhong, JC}, title = {Intestinal microbiota by angiotensin receptor blocker therapy exerts protective effects against hypertensive damages.}, journal = {iMeta}, volume = {3}, number = {4}, pages = {e222}, pmid = {39135690}, issn = {2770-596X}, abstract = {Dysbiosis of the gut microbiota has been implicated in hypertension, and drug-host-microbiome interactions have drawn considerable attention. However, the influence of angiotensin receptor blocker (ARB)-shaped gut microbiota on the host is not fully understood. In this work, we assessed the alterations of blood pressure (BP), vasculatures, and intestines following ARB-modified gut microbiome treatment and evaluated the changes in the intestinal transcriptome and serum metabolome in hypertensive rats. Hypertensive patients with well-controlled BP under ARB therapy were recruited as human donors, spontaneously hypertensive rats (SHRs) receiving normal saline or valsartan were considered animal donors, and SHRs were regarded as recipients. Histological and immunofluorescence staining was used to assess the aorta and small intestine, and 16S rRNA amplicon sequencing was performed to examine gut bacteria. Transcriptome and metabonomic analyses were conducted to determine the intestinal transcriptome and serum metabolome, respectively. Notably, ARB-modified fecal microbiota transplantation (FMT), results in marked decreases in systolic BP levels, collagen deposition and reactive oxygen species accumulation in the vasculature, and alleviated intestinal structure impairments in SHRs. These changes were linked with the reconstruction of the gut microbiota in SHR recipients post-FMT, especially with a decreased abundance of Lactobacillus, Aggregatibacter, and Desulfovibrio. Moreover, ARB-treated microbes contributed to increased intestinal Ciart, Per1, Per2, Per3, and Cipc gene levels and decreased Nfil3 and Arntl expression were detected in response to ARB-treated microbes. More importantly, circulating metabolites were dramatically reduced in ARB-FMT rats, including 6beta-Hydroxytestosterone and Thromboxane B2. In conclusion, ARB-modified gut microbiota exerts protective roles in vascular remodeling and injury, metabolic abnormality and intestinal dysfunctions, suggesting a pivotal role in mitigating hypertension and providing insights into the cross-talk between antihypertensive medicines and the gut microbiome.}, }
@article {pmid39135640, year = {2024}, author = {Cao, H and Zhang, D and Wang, P and Wang, Y and Shi, C and Wu, H and Du, H and Zhang, W and Gou, Z and Zhou, H and Wang, S}, title = {Gut microbiome: a novel preventive and therapeutic target for prostatic disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1431088}, pmid = {39135640}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; *Prostatic Diseases/microbiology/prevention &amp; control/therapy ; Humans ; Male ; Inflammation/microbiology/pathology ; Metabolome ; Diet ; Fecal Microbiota Transplantation ; Medicine, Chinese Traditional ; }, abstract = {The human gut microbiome (GM) impacts various physiological processes and can lead to pathological conditions and even carcinogenesis if homeostasis is disrupted. Recent studies have indicated a connection between the GM and prostatic disease. However, the underlying mechanisms are still unclear. This review aims to provide a summary of the existing information regarding the connection between the GM and various prostatic conditions such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), benign prostatic hyperplasia (BPH), and prostate cancer (PCa). Furthermore, the review aims to identify possible pathogenic mechanisms and suggest potential ways of targeting GM to prevent and treat prostatic disease. Due to the complexity of the mechanism between GM and prostatic diseases, additional research is required to comprehend the association between the two. This will lead to more effective treatment options for prostatic disease.}, }
@article {pmid39135376, year = {2024}, author = {Wang, J and Jiang, M and Li, X and Ye, Y and Xie, Y and Wu, T and Chen, Y and Yu, H and Wu, H and Yang, Z and Zhou, E}, title = {Inulin Supplementation Alleviates Ochratoxin A-Induced Kidney Injury through Modulating Intestinal Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {33}, pages = {18682-18696}, doi = {10.1021/acs.jafc.4c04382}, pmid = {39135376}, issn = {1520-5118}, mesh = {*Ochratoxins/toxicity ; Animals ; *Inulin/administration &amp; dosage ; *Gastrointestinal Microbiome/drug effects ; *Chickens ; *Kidney/drug effects/metabolism ; Bacteria/classification/isolation &amp; purification/genetics/drug effects/metabolism ; Dietary Supplements/analysis ; Fatty Acids, Volatile/metabolism ; Poultry Diseases/microbiology/drug therapy/prevention &amp; control ; Animal Feed/analysis ; Male ; Kidney Diseases/metabolism/prevention &amp; control/etiology ; }, abstract = {Ochratoxin A (OTA) is a prevalent mycotoxin found in feed that causes significant kidney injury in animals. Further investigation was needed to devise strategies for treating OTA-induced kidney damage through the gut-kidney axis. Evidence indicates the crucial role of intestinal microbiota in kidney damage development. Inulin, a dietary fiber, protects kidneys by modulating intestinal microbiota and promoting short-chain fatty acid (SCFA) production. However, its precise mechanism in OTA-induced kidney damage remained unclear. In this study, chickens were orally administered OTA and inulin for 2 weeks to investigate inulin's effects on OTA-induced kidney damage and underlying mechanisms. The alteration of intestinal microbiota, SCFAs contents, and SCFA receptors was further analyzed. Results demonstrated that inulin supplementation influenced intestinal microbiota, increased SCFAs production, and mitigated OTA-induced kidney damage in chickens. The importance of microbiota in mediating inulin's renal protection was further confirmed by antibiotic and fecal microbiota transplantation experiments. Additionally, inulin exhibited antioxidant and anti-inflammatory properties, alleviating NLRP3 inflammasome activation and pyroptosis. In summary, inulin protected chickens from OTA-induced kidney damage, which might provide a potential strategy to mitigate the harmful effects of mycotoxins through prebiotics and safeguard renal health.}, }
@article {pmid39135306, year = {2024}, author = {Zuo, S and Huang, Y and Zou, J}, title = {The role of the gut microbiome in modulating immunotherapy efficacy in colorectal cancer.}, journal = {IUBMB life}, volume = {76}, number = {12}, pages = {1050-1057}, doi = {10.1002/iub.2908}, pmid = {39135306}, issn = {1521-6551}, support = {2023AH051777//Key Project in Natural Science Research in Higher Education Institutions of Anhui Province/ ; WK2022ZF29//Key Project of Natural Science Foundation of Wannan Medical College/ ; WHWJ2023z007//Key Research Project of Wuhu Municipal Health Commission/ ; DFJH2022018//Climbing Scientific Peak Project for Talents, the Second Affiliated Hospital of Wannan Medical College/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Colorectal Neoplasms/immunology/therapy/microbiology/pathology ; *Immunotherapy/methods ; *Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; }, abstract = {This systematic literature review and meta-analysis provide an overview of the critical role of gut microbiota in modulating the efficacy of immunotherapy for colorectal cancer. Gut microbes influence host immune responses through multiple mechanisms including modulation of immune cell activity, metabolite action, and immune tolerance. The ability of specific gut microbes to improve the efficacy of immune checkpoint inhibitors has been linked to their ability to improve gut barrier function, modulate immune cell activity, and produce key immunomodulatory metabolites such as short-chain fatty acids. In addition, the composition and diversity of the gut microbiota are strongly associated with the efficacy of immunotherapies, demonstrating the potential to improve therapeutic response by modifying the gut microbiota. This paper also discusses the prospect of manipulating the gut microbiota through strategies such as fecal microbial transplantation, probiotic supplementation, and dietary modifications to optimize the efficacy of immunotherapy.}, }
@article {pmid39134825, year = {2025}, author = {Ni, Y and Tong, Q and Xu, M and Gu, J and Ye, H}, title = {Gut Microbiota-Induced Modulation of the Central Nervous System Function in Parkinson's Disease Through the Gut-Brain Axis and Short-Chain Fatty Acids.}, journal = {Molecular neurobiology}, volume = {62}, number = {2}, pages = {2480-2492}, pmid = {39134825}, issn = {1559-1182}, support = {Y20170064//Wenzhou Science and Technology Bureau Project/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Fatty Acids, Volatile/metabolism ; *Parkinson Disease/microbiology/physiopathology/metabolism ; Humans ; Male ; *Brain/metabolism/physiopathology ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Receptors, G-Protein-Coupled/metabolism ; Dopaminergic Neurons/metabolism/pathology ; Mice ; *Brain-Gut Axis/physiology ; Dopamine/metabolism ; }, abstract = {Recent insights into Parkinson's disease (PD), a progressive neurodegenerative disorder, suggest a significant influence of the gut microbiome on its pathogenesis and progression through the gut-brain axis. This study integrates 16S rRNA sequencing, high-throughput transcriptomic sequencing, and animal model experiments to explore the molecular mechanisms underpinning the role of gut-brain axis in PD, with a focus on short-chain fatty acids (SCFAs) mediated by the SCFA receptors FFAR2 and FFAR3. Our findings highlighted prominent differences in the gut microbiota composition between PD patients and healthy individuals, particularly in taxa such as Escherichia_Shigella and Bacteroidetes, which potentially impact SCFA levels through secondary metabolite biosynthesis. Notably, fecal microbiota transplantation (FMT) from healthy to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models significantly improved motor function, enhanced dopamine and serotonin levels in the striatum, and increased the number of dopaminergic neurons in the substantia nigra while reducing glial cell activation. This therapeutic effect was associated with increased levels of SCFAs such as acetate, propionate, and butyrate in the gut of MPTP-lesioned mice. Moreover, transcriptomic analyses revealed upregulated expression of FFAR2 and FFAR3 in MPTP-lesioned mice, indicating their crucial role in mediating the benefits of FMT on the central nervous system. These results provide compelling evidence that gut microbiota and SCFAs play a critical role in modulating the gut-brain axis, offering new insights into PD's etiology and potential targets for therapeutic intervention.}, }
@article {pmid39128572, year = {2024}, author = {Uzan-Yulzari, A and Turjeman, S and Moadi, L and Getselter, D and Sharon, E and Rautava, S and Isolauri, E and Khatib, S and Elliott, E and Koren, O}, title = {A gut reaction? The role of the microbiome in aggression.}, journal = {Brain, behavior, and immunity}, volume = {122}, number = {}, pages = {301-312}, doi = {10.1016/j.bbi.2024.08.011}, pmid = {39128572}, issn = {1090-2139}, mesh = {*Aggression/physiology ; Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Fecal Microbiota Transplantation/methods ; Male ; *Brain/metabolism ; Anti-Bacterial Agents/pharmacology ; Behavior, Animal/physiology ; Germ-Free Life ; Mice, Inbred C57BL ; Humans ; }, abstract = {Recent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. Here, we compared behavior profiles of control, germ-free (GF), and antibiotic-treated mice, as well as re-colonized GF mice to understand the impact of the gut microbiome on aggression using the resident-intruder paradigm. Our findings revealed a link between gut microbiome depletion and higher aggression, accompanied by notable changes in urine metabolite profiles and brain gene expression. This study extends beyond classical murine models to humanized mice to reveal the clinical relevance of early-life antibiotic use on aggression. Fecal microbiome transplant from infants exposed to antibiotics in early life (and sampled one month later) into mice led to increased aggression compared to mice receiving transplants from unexposed infants. This study sheds light on the role of the gut microbiome in modulating aggression and highlights its potential avenues of action, offering insights for development of therapeutic strategies for aggression-related disorders.}, }
@article {pmid39126667, year = {2024}, author = {Yang, L and Gao, Y and Gong, J and Su, Q and Guo, Z and Farag, MA and Xiao, J}, title = {Myricetin ameliorates prediabetes through gut microbiota-SCFAs-Gpr43 axis.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/10408398.2024.2386450}, pmid = {39126667}, issn = {1549-7852}, }
@article {pmid39126020, year = {2024}, author = {Alexandrescu, L and Nicoara, AD and Tofolean, DE and Herlo, A and Nelson Twakor, A and Tocia, C and Trandafir, A and Dumitru, A and Dumitru, E and Aftenie, CF and Preotesoiu, I and Dina, E and Tofolean, IT}, title = {Healing from Within: How Gut Microbiota Predicts IBD Treatment Success-A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {15}, pages = {}, pmid = {39126020}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Inflammatory Bowel Diseases/microbiology/therapy ; *Fecal Microbiota Transplantation/methods ; Treatment Outcome ; Probiotics/therapeutic use ; Antibodies, Monoclonal, Humanized ; }, abstract = {Recent research indicates that the microbiome has a significant impact on the progression of inflammatory bowel disease (IBD) and that creating therapies that change its composition could positively impact the outcomes of IBD treatment. This review summarizes the results of extensive studies that examined IBD patients undergoing several therapies, including anti-TNF medication, vedolizumab, ustekinumab, probiotics, and fecal microbiota transplantation (FMT), and the alterations in their gut microbiota's composition and function. The objective was to investigate the variety and effectiveness of microbial species in order to discover new biomarkers or therapeutic targets that could improve the outcome of treatment for these patients. This research aimed to offer useful insights into personalized medicine techniques for managing IBD. Beneficial bacteria such as Faecalibacterium prausnitzii and Roseburia have been consistently linked to favorable clinical outcomes, whereas pathogenic bacteria such as Escherichia coli and Clostridioides difficile are associated with worsening disease conditions. Although many studies have examined the role of gut microbiota in IBD, there is still a need for more targeted research on the connection between specific microbial communities and treatment outcomes. This study sought to address this gap by exploring the intricate relationship between the gut microbiota composition and the effectiveness of IBD medications.}, }
@article {pmid39122767, year = {2024}, author = {Zhang, B and Magnaye, KM and Stryker, E and Moltzau-Anderson, J and Porsche, CE and Hertz, S and McCauley, KE and Smith, BJ and Zydek, M and Pollard, KS and Ma, A and El-Nachef, N and Lynch, SV}, title = {Sustained mucosal colonization and fecal metabolic dysfunction by Bacteroides associates with fecal microbial transplant failure in ulcerative colitis patients.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {18558}, pmid = {39122767}, issn = {2045-2322}, support = {K12 GM081266-11/GM/NIGMS NIH HHS/United States ; T32 DK007007/DK/NIDDK NIH HHS/United States ; 1563159//National Science Foundation/ ; T32 DK007762/DK/NIDDK NIH HHS/United States ; K12 GM081266/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Colitis, Ulcerative/microbiology/therapy/metabolism ; *Fecal Microbiota Transplantation ; Male ; Female ; *Feces/microbiology ; *Bacteroides/genetics ; Adult ; *Intestinal Mucosa/microbiology/metabolism ; Middle Aged ; Gastrointestinal Microbiome ; Treatment Failure ; RNA, Ribosomal, 16S/genetics ; Metabolome ; }, abstract = {Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure.}, }
@article {pmid39121607, year = {2024}, author = {Qiu, L and Yan, C and Yang, Y and Liu, K and Yin, Y and Zhang, Y and Lei, Y and Jia, X and Li, G}, title = {Morin alleviates DSS-induced ulcerative colitis in mice via inhibition of inflammation and modulation of intestinal microbiota.}, journal = {International immunopharmacology}, volume = {140}, number = {}, pages = {112846}, doi = {10.1016/j.intimp.2024.112846}, pmid = {39121607}, issn = {1878-1705}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/chemically induced/microbiology/immunology/pathology ; *Gastrointestinal Microbiome/drug effects ; *Flavonoids/pharmacology/therapeutic use ; *Dextran Sulfate ; Mice ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Anti-Inflammatory Agents/therapeutic use/pharmacology ; Colon/pathology/drug effects/microbiology/immunology ; NF-kappa B/metabolism ; Fecal Microbiota Transplantation ; Humans ; Flavones ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory condition with recurrent and challenging symptoms. Effective treatments are lacking, making UC management a critical research area. Morin (MO), a flavonoid from the Moraceae family, shows potential as an anti-UC agent, but its mechanisms are not fully understood. Using a dextran sulfate sodium (DSS)-induced UC mouse model, we employed network pharmacology to predict MO's therapeutic effects. Assessments included changes in body weight, disease activity index (DAI), and colon length. Immunofluorescence, hematoxylin and eosin (H&amp;E), and PAS staining evaluated colon damage. ELISA and western blot analyzed inflammatory factors, tight junction (TJ)-associated proteins (Claudin-3, Occludin, ZO-1), and Mitogen-Activated Protein Kinase (MAPK)/ Nuclear Factor kappa B (NF-κB) pathways. 16S rRNA sequencing assessed gut microbiota diversity, confirmed by MO's modulation via Fecal Microbial Transplantation (FMT). Early MO intervention reduced UC severity by improving weight, DAI scores, and colon length, increasing goblet cells, enhancing barrier function, and inhibiting MAPK/NF-κB pathways. MO enriched gut microbiota, favoring beneficial bacteria like Muribaculaceae and Erysipelotrichaceae while reducing harmful Erysipelotrichaceae and Muribaculaceae. This study highlights MO's potential in UC management through inflammation control, mucosal integrity maintenance, and gut flora modulation.}, }
@article {pmid39118149, year = {2024}, author = {Li, DH and Li, ZW and Sun, Q and Wang, L and Ning, SB}, title = {Lower fecal microbiota transplantation ameliorates ulcerative colitis by eliminating oral-derived Fusobacterium nucleatum and virulence factor.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {42}, pmid = {39118149}, issn = {1757-4749}, abstract = {BACKGROUND: Recently, the oral oncobacterium Fusobacterium nucleatum (F. nucleatum), has been linked with ulcerative colitis (UC). Here, we aim to investigate whether Fecal Microbiota Transplantation (FMT) can alleviate UC by restoring gut microbiota and eliminating oral-derived F. nucleatum and virulence factor fadA.<br><br>METHOD: C57BL/6J mice were randomly divided into a healthy control group (HC), Dextran Sulfate Sodium group (DSS), oral inoculation group (OR), upper FMT group (UFMT), and lower FMT group (LFMT). Disease activity index, body weight, survival rate, and histopathological scores were used to measure the severity of colitis. The function of the intestinal mucosal barrier was evaluated by performing immunohistochemical staining of the tight junction protein Occludin. Real-time PCR was used to assess the relative abundance of the nusG gene and the virulence gene fadA. Cytokine levels were detected by ELISA. Full-length sequencing of 16S rRNA was used to analyze the changes and composition of gut microbiota.<br><br>FINDINGS: Oral incubation of F. nucleatum further exacerbated the severity of colitis and gut dysbiosis. Peptostreptococcaceae, Enterococcaceae, and Escherichia coli were significantly enriched in OR mice. However, LFMT mice showed an obvious decrease in disease activity and were more effective in restoring gut microbiota and eliminating F. nucleatum than UFMT mice. Bacteroidota, Lachnospiraceae, and Prevotellaceae were mainly enriched bacteria in LFMT mice. In addition, Genera such as Lactobacillus, Allobaculum, and Bacteroidales were found negative correlation with TNF-&#x3b1;, IL-1&#x3b2;, and IL-6. Genera like Romboutsia, Escherichia Shigella, Enterococcus, and Clostridium were found positively correlated with TNF-&#x3b1;, IL-1&#x3b2;, and IL-6.<br><br>CONCLUSIONS: Oral incubation of F. nucleatum further exacerbates the severity and dysbiosis in DSS-induced colitis mice. Besides, lower tract FMT can ameliorate colitis by restoring the gut microbiota diversity and eliminating F. nucleatum and virulence factor&#xa0;fadA.}, }
@article {pmid39117173, year = {2024}, author = {Bell, J and Raidal, S and Peters, A and Hughes, KJ}, title = {Storage of equine faecal microbiota transplantation solution has minimal impact on major bacterial communities and structure.}, journal = {Veterinary journal (London, England : 1997)}, volume = {307}, number = {}, pages = {106220}, doi = {10.1016/j.tvjl.2024.106220}, pmid = {39117173}, issn = {1532-2971}, mesh = {Animals ; Horses ; *Feces/microbiology ; *Fecal Microbiota Transplantation/veterinary ; RNA, Ribosomal, 16S/analysis ; Bacteria/genetics ; Gastrointestinal Microbiome ; Microbiota ; }, abstract = {Management of diarrhoea in horses is usually non-specific and supportive. Faecal microbiota transplantations (FMT) are used to manage dysbiosis in horses with diarrhoea. There are few studies investigating the effects of storage on prepared FMT solutions. This study was an in vitro non-randomised controlled experiment that investigated the effects of FMT solution preparation and storage on the faecal microbiota. Fresh faeces were collected from five healthy adult horses and used for DNA extraction and preparation of FMT. From each FMT, seven aliquots were collected and DNA was extracted immediately after FMT preparation (0 hr), after storage at 4 °C for 24, 48 or 72 hours, and after storage at -20°C for 7 days, 14 days or 28 days. The extracted DNA was used for 16 S rRNA gene sequencing. The relative abundance, alpha diversity and beta diversity between fresh faeces and FMT 0 hr showed no differences (P ≥ 0.05). There were minimal changes in the microbiota of FMT stored at 4°C for up to 72 hours and -20°C for up to 28 days. The results of this study indicate that preparation of equine FMT solution has minimal effect on the microbiota in comparison to fresh faeces. FMT solution can be stored at 4°C for up to 3 days and -20°C for 28 days without major change in microbiota.}, }
@article {pmid39113144, year = {2024}, author = {Han, L and Sun, X and Kong, J and Li, J and Feng, K and Bai, Y and Wang, X and Zhu, Z and Yang, F and Chen, Q and Zhang, M and Yue, B and Wang, X and Fu, L and Chen, Y and Yang, Q and Wang, S and Xin, Q and Sun, N and Zhang, D and Zhou, Y and Gao, Y and Zhao, J and Jiang, Y and Guo, R}, title = {Multi-omics analysis reveals a feedback loop amplifying immune responses in acute graft-versus-host disease due to imbalanced gut microbiota and bile acid metabolism.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {746}, pmid = {39113144}, issn = {1479-5876}, support = {82100240//National Natural Science Foundation of China/ ; }, mesh = {*Bile Acids and Salts/metabolism ; Humans ; *Graft vs Host Disease/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Female ; Male ; *Feces/microbiology ; Middle Aged ; Acute Disease ; Adult ; Feedback, Physiological ; Immunity ; Metabolomics ; Hematopoietic Stem Cell Transplantation ; Multiomics ; }, abstract = {Acute graft-versus-host disease (aGVHD) is primarily driven by allogeneic donor T cells associated with an altered composition of the host gut microbiome and its metabolites. The severity of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not solely determined by the host and donor characteristics; however, the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we decoded the immune cell atlas of 12 patients who underwent allo-HSCT: six with aGVHD and six with non-aGVHD. We performed a fecal microbiota (16SrRNA sequencing) analysis to investigate the fecal bacterial composition of 82 patients: 30 with aGVHD and 52 with non-aGVHD. Fecal samples from these patients were analyzed for bile acid metabolism. Through multi-omic analysis, we identified a feedback loop involving "immune cell-gut microbes-bile acid metabolites" contributing to heightened immune responses in patients with aGVHD. The dysbiosis of the gut microbiota and disruption of bile acid metabolism contributed to an exaggerated interleukin-1 mediated immune response. Our findings suggest that resistin and defensins are crucial in mitigating against aGVHD. Therefore, a comprehensive multi-omic atlas incorporating immune cells, gut microbes, and bile acid metabolites was developed in this study and used to propose novel, non-immunosuppressive approaches to prevent aGVHD.}, }
@article {pmid39113097, year = {2024}, author = {Gray, SM and Moss, AD and Herzog, JW and Kashiwagi, S and Liu, B and Young, JB and Sun, S and Bhatt, AP and Fodor, AA and Balfour Sartor, R}, title = {Mouse adaptation of human inflammatory bowel diseases microbiota enhances colonization efficiency and alters microbiome aggressiveness depending on the recipient colonic inflammatory environment.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {147}, pmid = {39113097}, issn = {2049-2618}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; NSF Cooperative Agreement No. EEC-2133504//The Engineering Research Centers Program of the National Science Foundation/ ; T32DK007737//NIH/NIDDK/ ; T32 DK007737/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/microbiology ; *Disease Models, Animal ; *Dysbiosis/microbiology ; *Interleukin-10/genetics ; Colitis/microbiology ; Feces/microbiology ; Colon/microbiology ; Mice, Knockout ; Mice, Inbred C57BL ; Female ; Bacteria/classification/genetics/isolation &amp; purification ; Inflammation ; Male ; }, abstract = {BACKGROUND: Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis.<br><br>RESULTS: Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota-associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10[-/-] mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10[-/-] mice. Engraftment of human-to-mouse FMT stochastically varied with individual transplantation events more than mouse-adapted FMT. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10[-/-] host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10[-/-] mice than the distinct microbiota reassembled in non-inflamed WT hosts.<br><br>CONCLUSIONS: Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated by gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer. Video Abstract.}, }
@article {pmid39111080, year = {2024}, author = {Zhu, J and Li, B and Fang, W and Zhou, X and Li, D and Jin, J and Li, W and Su, Y and Yuan, R and Ye, JM and Wu, R}, title = {Oral matrine alleviates CCl4-induced liver fibrosis via preserved HSP72 from modulated gut microbiota.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {178}, number = {}, pages = {117262}, doi = {10.1016/j.biopha.2024.117262}, pmid = {39111080}, issn = {1950-6007}, mesh = {Animals ; Male ; Mice ; Administration, Oral ; *Alkaloids/pharmacology ; *Carbon Tetrachloride ; Cell Line ; Dysbiosis ; Epithelial-Mesenchymal Transition/drug effects ; *Gastrointestinal Microbiome/drug effects ; *HSP72 Heat-Shock Proteins/metabolism ; *Liver Cirrhosis/drug therapy/pathology/metabolism/chemically induced ; *Matrines ; Mice, Inbred C57BL ; *Quinolizines/pharmacology ; Transforming Growth Factor beta1/metabolism ; }, abstract = {Hepatic fibrosis is intricately associated with dysregulation of gut microbiota and host metabolomes. Our previous studies have demonstrated that matrine can effectively reduce hepatosteatosis and associated disorders. However, it is poorly understood whether the gut microbiota involved in the attenuation of liver fibrosis by matrine. Herein we explored a novel mechanism of how oral administration of matrine alleviates liver fibrosis by modulating gut microbiota. Administration of matrine not only potently ameliorated liver fibrosis in carbon tetrachloride (CCl4)-induced mice, but also significantly preserved hepatic heat shock protein 72 (HSP72) in vivo and in vitro. Matrine was failed to reduce liver fibrosis when HSP72 upregulation was blocked by the HSP72 antagonist VER-155008. Also, consumption of matrine significantly alleviated gut dysbiosis and fecal metabonomic changes in CCl4-treated mice. Transplanted the faces of matrine-treated mice induced a remarkable upregulation of HSP72 and remission of fibrosis in liver in CCl4-exposed mice and inhibition of TGF-β1-induced inflammatory response and epithelial-mesenchymal transition (EMT) in AML-12 cells. Furthermore, deficiency of HSP72 partly reversed the intestinal microbial composition that prevented matrine from reducing CCl4-induced liver fibrosis in mice. This study reveals the "gut microbiota-hepatic HSP72" axis as a key mechanism of matrine in reducing liver fibrosis and suggest that this axis may be targeted for developing other new therapies for liver fibrosis.}, }
@article {pmid39110590, year = {2024}, author = {He, Y and Zhao, C and Su, N and Yang, W and Yang, H and Yuan, C and Zhang, N and Hu, X and Fu, Y}, title = {Disturbances of the gut microbiota-derived tryptophan metabolites as key actors in vagotomy-induced mastitis in mice.}, journal = {Cell reports}, volume = {43}, number = {8}, pages = {114585}, doi = {10.1016/j.celrep.2024.114585}, pmid = {39110590}, issn = {2211-1247}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Tryptophan/metabolism ; Female ; *Vagotomy ; Mice ; *Mastitis/metabolism/microbiology ; Receptors, Aryl Hydrocarbon/metabolism ; Vagus Nerve/metabolism ; NF-kappa B/metabolism ; Dysbiosis/microbiology/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Mammary Glands, Animal/microbiology/metabolism/pathology ; }, abstract = {Previous studies have demonstrated that gut microbiota dysbiosis promotes the development of mastitis. The interaction of the vagus nerve and gut microbiota endows host homeostasis and regulates disease development, but whether the vagus nerve participates in the pathogenesis of mastitis is unclear. Here, vagotomized mice exhibit disruption of the blood-milk barrier and mammary gland inflammation. Notably, mastitis and barrier damage caused by vagotomy are dependent on the gut microbiota, as evidenced by antibiotic treatment and fecal microbiota transplantation. Vagotomy significantly alters the gut microbial composition and tryptophan metabolism and reduces the 5-hydroxyindole acetic acid (5-HIAA) level. Supplementation with 5-HIAA alleviates vagotomy-induced mastitis, which is associated with the activation of the aryl hydrocarbon receptor (AhR) and subsequent inhibition of the NF-κB pathway. Collectively, our findings indicate the important role of the vagus-mediated gut-mammary axis in the pathogenesis of mastitis and imply a potential strategy for the treatment of mastitis by targeting the vagus-gut microbiota interaction.}, }
@article {pmid39109266, year = {2024}, author = {Li, Q and Liu, Y and Zhang, Z and Zhang, S and Ding, X and Zhang, F}, title = {Washed Microbiota Transplantation Improves the Sleep Quality in Patients with Inflammatory Bowel Disease.}, journal = {Nature and science of sleep}, volume = {16}, number = {}, pages = {1141-1152}, pmid = {39109266}, issn = {1179-1608}, abstract = {PURPOSE: There is scarce evidence to support the effectiveness of faecal microbiota transplantation (FMT) in improving sleep among individuals with inflammatory bowel disease (IBD). Our study aimed to evaluate the effect of washed microbiota transplantation (WMT) (the new method of FMT) on the sleep of patients with IBD in short term.<br><br>PATIENTS AND METHODS: This prospective study was conducted as part of two interventional clinical trials (starting on February 2013 and expected to end on December 2025) and placed significant emphasis on evaluating sleep quality in patients with IBD. To measure subjective sleep, we used the Pittsburgh sleep quality index (PSQI). The primary endpoint was the PSQI score one month after WMT.<br><br>RESULTS: This stage study included 52 eligible patients evaluated by PSQI questionnaire who underwent WMT from January 2020 to March 2021 and 47 patients were enrolled for analysis. The age of the patients ranged from 13 to 60 years, with a mean of 33.4 years, and 57.4% (25/47) of the patients were male. The PSQI scores for all 47 patients one month after undergoing WMT were significantly lower (Cohen d = 0.59, p < 0.001) compared to the baseline. Moreover, baseline PSQI score was correlated with the difference value of the PSQI score before and after WMT (post-PSQI minus pre-PSQI) (r = 0.61, p < 0.05).<br><br>CONCLUSION: The study suggests that WMT might be a helpful intervention for improving the sleep quality of patients with IBD, encouraging clinicians to consider its use in clinical practice for addressing poor sleep in IBD patients.<br><br>CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; ID: NCT01793831, NCT01790061.}, }
@article {pmid39109116, year = {2024}, author = {Khalil, Z and Maher, S}, title = {The Impact of Microbiome Dysbiosis on Hematopoietic Stem Cell Transplantation Outcomes: A Review Article.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e63995}, pmid = {39109116}, issn = {2168-8184}, abstract = {Microbiome dysbiosis has emerged as a critical factor influencing the outcomes of hematopoietic stem cell transplantation (HSCT). This comprehensive review delves into the intricate relationship between microbiome composition and HSCT outcomes, highlighting the mechanisms through which dysbiosis impacts engraftment, graft-versus-host disease (GVHD), infection rates, and overall survival. The gut microbiome plays a pivotal role in modulating immune responses and maintaining intestinal homeostasis, both of which are crucial for the success of HSCT. This review aims to elucidate the underlying pathways and potential therapeutic strategies to mitigate adverse outcomes associated with microbiome imbalances in HSCT patients. Integrating microbiome modulation strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and antibiotic stewardship into clinical practice can significantly improve patient outcomes and quality of life post-transplantation.}, }
@article {pmid39107366, year = {2024}, author = {Zhang, YJ and Bousvaros, A and Docktor, M and Kaplan, AL and Rufo, PA and Leier, M and Weatherly, M and Zimmerman, L and Nguyen, LTT and Barton, B and Russell, G and Alm, EJ and Kahn, SA}, title = {Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after fecal microbiota transplant in inflammatory bowel disease.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {18188}, pmid = {39107366}, issn = {2045-2322}, support = {K12 HD052896/HD/NICHD NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; 5K12HD052896//National Institute of Child Health and Human Development/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Adult ; Adolescent ; Female ; Male ; Young Adult ; *Lactobacillus ; Double-Blind Method ; Inflammatory Bowel Diseases/therapy/microbiology ; Gastrointestinal Microbiome ; Pilot Projects ; Feces/microbiology ; Treatment Outcome ; Crohn Disease/therapy/microbiology ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Colitis, Ulcerative/therapy/microbiology ; }, abstract = {Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14-29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3-92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.}, }
@article {pmid39106569, year = {2024}, author = {Chen, Y and Zeng, Q and Luo, Y and Song, M and He, X and Sheng, H and Gao, X and Zhu, Z and Sun, J and Cao, C}, title = {Polystyrene microplastics aggravate radiation-induced intestinal injury in mice.}, journal = {Ecotoxicology and environmental safety}, volume = {283}, number = {}, pages = {116834}, doi = {10.1016/j.ecoenv.2024.116834}, pmid = {39106569}, issn = {1090-2414}, mesh = {Animals ; *Microplastics/toxicity ; Mice ; *Polystyrenes/toxicity ; *Mice, Inbred C57BL ; Male ; Gastrointestinal Microbiome/drug effects/radiation effects ; Intestines/radiation effects/drug effects/pathology ; Intestine, Small/radiation effects/drug effects/pathology ; Radiation Injuries/pathology ; }, abstract = {Radiotherapy is a common treatment for abdominal and pelvic tumors, while the radiation-induced intestinal injury (RIII) is one of the major side-effects of radiotherapy, which reduces the life quality and impedes the treatment completion of cancer patients. Previous studies have demonstrated that environmental pollutant microplastics led to various kinds of injury in the gut, but its effects on RIII are still uncovered. In this study, we fed the C57BL/6J mice with distilled water or 50 μg/d polystyrene microplastics (PSMPs) for 17 days and exposed the mice to total abdominal irradiation (TAI) at day 14. Then the severity of RIII was examined by performing histopathological analysis and microbial community analysis. The results demonstrated that PSMPs significantly aggravated RIII in small intestine rather than colon of mice upon TAI. PSMPs increased levels of the histopathological damage and the microbial community disturbance in mice small intestine, shown by the overabundance of Akkermansiaceae and the decrease of microflora including Lactobacillaceae, Muribaculaceae and Bifidobacteriaceae. In conclusion, our results suggested that more microplastics exposure might led to more severe RIII, which should be considered in patients' daily diet adjustment and clinical radiotherapy plan evaluation. Furthermore, this study also called for the further researches to uncover the underlying mechanism and develop novel strategies to attenuate RIII in mice intestine.}, }
@article {pmid39105259, year = {2024}, author = {Jiang, H and Yu, Y and Hu, X and Du, B and Shao, Y and Wang, F and Chen, L and Yan, R and Li, L and Lv, L}, title = {The fecal microbiota of patients with primary biliary cholangitis (PBC) causes PBC-like liver lesions in mice and exacerbates liver damage in a mouse model of PBC.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2383353}, pmid = {39105259}, issn = {1949-0984}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Mice ; *Liver Cirrhosis, Biliary/microbiology/pathology/metabolism ; *Disease Models, Animal ; *Liver/pathology/metabolism/microbiology ; *Feces/microbiology ; Female ; Bacteria/classification/isolation &amp; purification/genetics ; Fecal Microbiota Transplantation ; Male ; Bile Acids and Salts/metabolism ; Transcriptome ; Mice, Inbred C57BL ; }, abstract = {The role of the gut microbiota in the occurrence and progression of primary biliary cholangitis (PBC) is not fully understood. First, the fecal microbiota of patients with PBC (n = 4) (PBC-FMT) or healthy individuals (n = 3) (HC-FMT) was transplanted into pseudo germ-free mice or 2OA-BSA-induced PBC models. The functions, histology and transcriptome of the liver, and microbiota and metabolome of the feces were analyzed. Second, the liver transcriptomes of PBC patients (n = 7) and normal individuals (n = 7) were analyzed. Third, the liver transcriptomes of patients with other liver diseases were collected from online databases and compared with our human and mouse data. Our results showed that PBC-FMT increased the serum ALP concentration, total bile acid content, liver injury and number of disease-related pathways enriched with upregulated liver genes in pseudo germ-free mice and increased the serum glycylproline dipeptidyl aminopeptidase level and liver damage in a 2OA-BSA-induced PBC model. The gut microbiota and metabolome differed between PBC-FMT and HC-FMT mice and reflected those of their donors. PBC-FMT tended to upregulate hepatic immune and signal transduction pathways but downregulate metabolic pathways, as in some PBC patients. The hematopoietic cell lineage, Toll-like receptor, and PPAR signaling pathway were not affected in patients with alcoholic hepatitis, HBV, HCV, HCV cirrhosis, or NASH, indicating their potential roles in the gut microbiota affecting PBC. In conclusion, the altered gut microbiota of PBC patients plays an important role in the occurrence and progression of PBC. The improvement of the gut microbiota is worthy of in-depth research and promotion as a critical aspect of PBC prevention and treatment.}, }
@article {pmid39105129, year = {2024}, author = {Aslam, R and Herrles, L and Aoun, R and Pioskowik, A and Pietrzyk, A}, title = {Link between gut microbiota dysbiosis and childhood asthma: Insights from a systematic review.}, journal = {The journal of allergy and clinical immunology. Global}, volume = {3}, number = {3}, pages = {100289}, pmid = {39105129}, issn = {2772-8293}, abstract = {Asthma, a chronic inflammatory disorder of the airways, is a prevalent childhood chronic disease with a substantial global health burden. The complex etiology and pathogenesis of asthma involve genetic and environmental factors, posing challenges in diagnosis, severity prediction, and therapeutic strategies. Recent studies have highlighted the significant role of the gut microbiota and its interaction with the immune system in the development of asthma. Dysbiosis, an imbalance in microbial composition, has been associated with respiratory diseases through the gut-lung axis. This axis is an interaction between the gut and lungs, allowing microbial metabolites to influence the host immune system. This systematic review examines the association between gut microbiota composition, measured using 16S rRNA sequencing, during infancy and childhood, and the subsequent development of atopic wheeze and asthma. The results suggest that higher alpha diversity of bacteria such as Bifidobacterium, Faecalibacterium, and Roseburia may have protective effects against asthmatic outcomes. Conversely, lower relative abundances of bacteria like Bacteroides and certain fungi, including Malassezia, were associated with asthma. These findings highlight the potential of early screening and risk assessment of gut microbiota to identify individuals at risk of asthma. Furthermore, investigations targeting gut microbiota, such as dietary modifications and probiotic supplementation, may hold promise for asthma prevention and management. Future research should focus on identifying specific microbial signatures associated with asthma susceptibility and further investigate approaches like fecal microbiota transplantation. Understanding the role of gut microbiota in asthma pathogenesis can contribute to early detection and development of interventions to mitigate the risk of asthmatic pathogenesis in childhood.}, }
@article {pmid39104728, year = {2024}, author = {Webster, CI and Withycombe, JS and Bhutada, JS and Bai, J}, title = {Review of the microbiome and metabolic pathways associated with psychoneurological symptoms in children with cancer.}, journal = {Asia-Pacific journal of oncology nursing}, volume = {11}, number = {8}, pages = {100535}, pmid = {39104728}, issn = {2347-5625}, abstract = {Children with cancer often endure a range of psychoneurological symptoms (PNS), including pain, fatigue, cognitive impairment, anxiety, depressive symptoms, and sleep disturbance. Despite their prevalence, the underlying pathophysiology of PNS remains unclear. Hypotheses suggest an interplay between the gut microbiome and the functional metabolome, given the immune, neurological, and inflammatory influences these processes exert. This mini-review aims to provide a synopsis of the literature that examines the relationship between microbiome-metabolome pathways and PNS in children with cancer, drawing insights from the adult population when applicable. While there is limited microbiome research in the pediatric population, promising results in adult cancer patients include an association between lower microbial diversity and compositional changes, including decreased abundance of the beneficial microbes Fusicatenibacter, Ruminococcus, and Odoribacter, and more PNS. In pediatric patients, associations between peptide, tryptophan, carnitine shuttle, and gut microbial metabolism pathways and PNS outcomes were found. Utilizing multi-omics methods that combine microbiome and metabolome analyses provide insights into the functional capacity of microbiomes and their associated microbial metabolites. In children with cancer receiving chemotherapy, increased abundances of Intestinibacter and Megasphaera correlated with six metabolic pathways, notably carnitine shuttle and tryptophan metabolism. Interventions that target the underlying microbiome-metabolome pathway may be effective in reducing PNS, including the use of pre- and probiotics, fecal microbiome transplantation, dietary modifications, and increased physical activity. Future multi-omics research is needed to corroborate the associations between the microbiome, metabolome, and PNS outcomes in the pediatric oncology population.}, }
@article {pmid39104406, year = {2024}, author = {Adamberg, S and Rasmussen, TS and Larsen, SB and Mao, X and Nielsen, DS and Adamberg, K}, title = {Reproducible chemostat cultures to minimize eukaryotic viruses from fecal transplant material.}, journal = {iScience}, volume = {27}, number = {8}, pages = {110460}, pmid = {39104406}, issn = {2589-0042}, abstract = {Recent studies indicate an important role of bacteriophages for successful fecal microbiota transplantation (FMT). However, wider clinical applications of FMT are hampered by to donor variability and concerns of infection risks by bacteria and human viruses. To overcome these challenges, mouse cecal and human fecal material were propagated in a chemostat fermentation setup supporting multiplication of bacteria, and phages, while propagation of eukaryotic viruses will be prevented in the absence of eukaryotic host cells. The results showed decrease of the median relative abundance of viral contigs of classified eukaryotic viruses below 0.01%. The corresponding virome profiles showed dilution rate dependency, a reproducibility between biological replicates, and maintained high diversity regarding both the human and mouse inocula. This proof-of-concept cultivation approach may constitute the first step of developing novel therapeutic tools with high reproducibility and with low risk of infection from the donor material to target gut-related diseases.}, }
@article {pmid39097746, year = {2024}, author = {Mo, C and Lou, X and Xue, J and Shi, Z and Zhao, Y and Wang, F and Chen, G}, title = {The influence of Akkermansia muciniphila on intestinal barrier function.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {41}, pmid = {39097746}, issn = {1757-4749}, support = {82160366//National Natural Science Foundation of China/ ; 2021LCZXXFHX03//Yunnan Clinical Medical Center Open Project/ ; 202205AC160060//Yunnan Young and Middle-aged Academic and Technical Leaders Reserve Talent Project/ ; 2022YNKQ004//Yunnan Key Laboratory of Stomatology Open Project/ ; }, abstract = {Intestinal barriers play a crucial role in human physiology, both in homeostatic and pathological conditions. Disruption of the intestinal barrier is a significant factor in the pathogenesis of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. The profound influence of the gut microbiota on intestinal diseases has sparked considerable interest in manipulating it through dietary interventions, probiotics, and fecal microbiota transplantation as potential approaches to enhance the integrity of the intestinal barrier. Numerous studies have underscored the protective effects of specific microbiota and their associated metabolites. In recent years, an increasing body of research has demonstrated that Akkermansia muciniphila (A. muciniphila, Am) plays a beneficial role in various diseases, including diabetes, obesity, aging, cancer, and metabolic syndrome. It is gaining popularity as a regulator that influences the intestinal flora and intestinal barrier and is recognized as a 'new generation of probiotics'. Consequently, it may represent a potential target and promising therapy option for intestinal diseases. This article systematically summarizes the role of Am in the gut. Specifically, we carefully discuss key scientific issues that need resolution in the future regarding beneficial bacteria represented by Am, which may provide insights for the application of drugs targeting Am in clinical treatment.}, }
@article {pmid39096912, year = {2024}, author = {Feng, Y and Zheng, H and Yin, C and Liang, D and Zhang, S and Chen, J and Mai, F and Lan, Z and Zhu, M and Mai, Z and Shen, S and Jayawardana, T and Wu, R and Tang, W and Zhang, R and He, X and Zheng, S and Hu, Q and Han, Y and Yang, Y and Gong, S and Wang, Z and El-Omar, EM and Luo, W and Chen, X and Chen, G and Li, P and Chen, X}, title = {β-resorcylic acid released by Limosilactobacillus reuteri protects against cisplatin-induced ovarian toxicity and infertility.}, journal = {Cell reports. Medicine}, volume = {5}, number = {8}, pages = {101678}, pmid = {39096912}, issn = {2666-3791}, mesh = {Female ; Animals ; *Cisplatin/adverse effects/toxicity ; Mice ; *Limosilactobacillus reuteri ; *Primary Ovarian Insufficiency/chemically induced/pathology ; *Ovary/drug effects/pathology/metabolism ; Gastrointestinal Microbiome/drug effects ; Apoptosis/drug effects ; Fecal Microbiota Transplantation ; Oocytes/drug effects/metabolism ; Mice, Inbred C57BL ; Antineoplastic Agents/toxicity/adverse effects ; Granulosa Cells/drug effects/metabolism ; Disease Models, Animal ; Infertility ; }, abstract = {Chemotherapy-induced premature ovarian insufficiency (CIPOI) triggers gonadotoxicity in women undergoing cancer treatment, leading to loss of ovarian reserves and subfertility, with no effective therapies available. In our study, fecal microbiota transplantation in a cisplatin-induced POI mouse model reveals that a dysbiotic gut microbiome negatively impacts ovarian health in CIPOI. Multi-omics analyses show a significant decrease in Limosilactobacillus reuteri and its catabolite, β-resorcylic acid , in the CIPOI group in comparison to healthy controls. Supplementation with L. reuteri or β-RA mitigates cisplatin-induced hormonal disruptions, morphological damages, and reductions in follicular reserve. Most importantly, β-RA pre-treatment effectively preserves oocyte function, embryonic development, and fetus health, thereby protecting against chemotherapy-induced subfertility. Our results provide evidence that β-RA suppresses the nuclear accumulation of sex-determining region Y-box 7, which in turn reduces Bcl-2-associated X activation and inhibits granulosa cell apoptosis. These findings highlight the therapeutic potential of targeting the gut-ovary axis for fertility preservation in CIPOI.}, }
@article {pmid39096665, year = {2024}, author = {Garg, P and Bhasin, SL and Malhotra, P and Rana, SS and Singh, S and Sethi, J and Sehgal, R and Khurana, S and Datta, P}, title = {Multiplex PCR for gastrointestinal parasites in stool: Benchmarking against direct microscopy and simplex PCR.}, journal = {Diagnostic microbiology and infectious disease}, volume = {110}, number = {2}, pages = {116475}, doi = {10.1016/j.diagmicrobio.2024.116475}, pmid = {39096665}, issn = {1879-0070}, mesh = {Humans ; *Feces/parasitology ; *Multiplex Polymerase Chain Reaction/methods ; *Sensitivity and Specificity ; *Microscopy/methods ; *Giardia lamblia/genetics/isolation &amp; purification ; Adult ; *Entamoeba histolytica/genetics/isolation &amp; purification ; Female ; Male ; Middle Aged ; Cryptosporidium/genetics/isolation &amp; purification ; Child ; Young Adult ; Child, Preschool ; Intestinal Diseases, Parasitic/diagnosis/parasitology ; Adolescent ; Benchmarking ; Coinfection/parasitology/diagnosis ; Aged ; Diarrhea/parasitology/diagnosis ; Giardiasis/diagnosis/parasitology ; Molecular Diagnostic Techniques/methods ; Infant ; }, abstract = {PURPOSE: To develop and validate a multiplex conventional PCR assay to simultaneously detect Cryptosporidium spp., Entamoeba histolytica, and Giardia lamblia in diarrheal samples as a rapid, cost-effective, and sensitive diagnostic tool for prevalent co-infections for improved diagnostic accuracy and efficiency in resource-limited settings.<br><br>METHODS: Stool samples collected from patients with gastrointestinal symptoms after taking written consent, processed via wet mount, iodine mount, and PCR assays. Cohen's kappa statistical analysis was done to test agreement.<br><br>RESULT: Among 240 patients, 28.75% showed intestinal protozoa via Microscopy; Single-plex and multiplex PCR demonstrated 100% concordance, detecting 27.9%; confirmed by sequencing. Highest parasite positivity was observed in transplant and immunocompromised patients, with moderate to almost perfect agreement between microscopy and molecular methods.<br><br>CONCLUSION: Multiplex-conventional PCR offers superior sensitivity and specificity over microscopy and 100% concordance with single-plex PCR, enabling rapid, cost-effective diagnosis of multiple parasites from single stool sample. Its adoption could revolutionize parasitic infection management in routine diagnostics.}, }
@article {pmid39095306, year = {2025}, author = {Zugman, M and Wong, M and Jaime-Casas, S and Pal, SK}, title = {The gut microbiome and dietary metabolites in the treatment of renal cell carcinoma.}, journal = {Urologic oncology}, volume = {43}, number = {4}, pages = {244-253}, doi = {10.1016/j.urolonc.2024.07.003}, pmid = {39095306}, issn = {1873-2496}, mesh = {Humans ; *Carcinoma, Renal Cell/therapy/microbiology/metabolism/diet therapy ; *Gastrointestinal Microbiome ; *Kidney Neoplasms/microbiology/therapy/metabolism/diet therapy ; *Diet ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiome is interlinked with renal cell carcinoma (RCC) and its response to systemic treatment. Mounting data suggests that certain elements of the gut microbiome may correlate with improved outcomes. New generation sequencing techniques and advanced bioinformatic data curation are accelerating the investigation of specific markers and metabolites that could predict treatment response. A variety of new therapeutic strategies, such as fecal microbiota transplantation, probiotic supplements, and dietary interventions, are currently being developed to modify the gut microbiome and improve anticancer therapies in patients with RCC. This review discusses the preliminary evidence indicating the role of the microbiome in cancer treatment, the techniques and tools necessary for its proper study and some of the current forms with which the microbiome can be modulated to improve patient outcomes.}, }
@article {pmid39094622, year = {2024}, author = {Reisinger, A and Stübing, H and Suchodolski, JS and Pilla, R and Unterer, S and Busch, K}, title = {Comparing treatment effects on dogs with acute hemorrhagic diarrhea syndrome: fecal microbiota transplantation, symptomatic therapy, or antibiotic treatment.}, journal = {Journal of the American Veterinary Medical Association}, volume = {262}, number = {12}, pages = {1657-1665}, doi = {10.2460/javma.24.03.0153}, pmid = {39094622}, issn = {1943-569X}, mesh = {Animals ; Dogs ; Female ; Male ; *Anti-Bacterial Agents/therapeutic use ; *Diarrhea/complications/therapy/veterinary ; *Dog Diseases/therapy/microbiology ; *Fecal Microbiota Transplantation/veterinary ; Prospective Studies ; *Hemorrhage/complications/therapy/veterinary ; }, abstract = {OBJECTIVE: Dogs with acute hemorrhagic diarrhea syndrome (AHDS) present with similar clinical signs and histopathological findings as dogs with parvovirosis, in which fecal microbiota transplantation (FMT) has led to a significantly faster resolution of diarrhea and shorter hospitalization times. We investigated whether FMT results in faster clinical improvement and normalization of the intestinal microbiome compared to standard treatment.<br><br>ANIMALS: 32 client-owned dogs with AHDS.<br><br>METHODS: A prospective, double-anonymized clinical trial included 3 groups: symptomatic treatment (n = 12), FMT treatment (FMTT; 12), and antibiotic treatment (AT; 8). Clinical improvement was determined on the basis of AHDS index, changes in the microbiome based on the dysbiosis index, and PCR results for clostridial strains.<br><br>RESULTS: Overall, no significant differences in clinical scores between the treatment groups over time were detected except on day 2 (higher AHDS index in the AT group compared to FMTT group; P = .046). The dysbiosis index increased and P hiranonis decreased on day 1 in some dogs, but these changes were transient in the symptomatic treatment and FMTT groups. In the AT group, the dysbiosis index was persistently elevated and 4 of 8 dogs showed a reduced abundance of P hiranonis on day 42. In 67% of the dogs on day 1, NetF-encoding Clostridium perfringens was detected and enterotoxin-encoding strains increased, but these changes were transient in all dogs, regardless of therapy.<br><br>CLINICAL RELEVANCE: Overall, in dogs with AHDS, neither FMT nor AT resulted in faster clinical improvement. In addition, C perfringens strains are self-limiting and do not require antibiotic therapy.}, }
@article {pmid39087354, year = {2024}, author = {Zhang, H and Fu, L and Leiliang, X and Qu, C and Wu, W and Wen, R and Huang, N and He, Q and Cheng, Q and Liu, G and Cheng, Y}, title = {Beyond the Gut: The intratumoral microbiome's influence on tumorigenesis and treatment response.}, journal = {Cancer communications (London, England)}, volume = {44}, number = {10}, pages = {1130-1167}, pmid = {39087354}, issn = {2523-3548}, support = {82372943//National Natural Science Foundation of China/ ; 82303610//National Natural Science Foundation of China/ ; 2022JJ20095//Hunan Provincial Natural Science Foundation of China/ ; 2023RC3074//Hunan Youth Science and Technology Talent Project/ ; 2023MD734131//China Postdoctoral Science Foundation/ ; CSTB2023NSCQBHX0002//Chongqing Postdoctoral Science Foundation/ ; //Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University/ ; 2023CQBSHTB3095//Chongqing Postdoctoral Research Special Funding Project/ ; }, mesh = {Humans ; *Neoplasms/therapy/microbiology ; *Carcinogenesis ; *Gastrointestinal Microbiome ; Tumor Microenvironment ; Microbiota ; Animals ; }, abstract = {The intratumoral microbiome (TM) refers to the microorganisms in the tumor tissues, including bacteria, fungi, viruses, and so on, and is distinct from the gut microbiome and circulating microbiota. TM is strongly associated with tumorigenesis, progression, metastasis, and response to therapy. This paper highlights the current status of TM. Tract sources, adjacent normal tissue, circulatory system, and concomitant tumor co-metastasis are the main origin of TM. The advanced techniques in TM analysis are comprehensively summarized. Besides, TM is involved in tumor progression through several mechanisms, including DNA damage, activation of oncogenic signaling pathways (phosphoinositide 3-kinase [PI3K], signal transducer and activator of transcription [STAT], WNT/β-catenin, and extracellular regulated protein kinases [ERK]), influence of cytokines and induce inflammatory responses, and interaction with the tumor microenvironment (anti-tumor immunity, pro-tumor immunity, and microbial-derived metabolites). Moreover, promising directions of TM in tumor therapy include immunotherapy, chemotherapy, radiotherapy, the application of probiotics/prebiotics/synbiotics, fecal microbiome transplantation, engineered microbiota, phage therapy, and oncolytic virus therapy. The inherent challenges of clinical application are also summarized. This review provides a comprehensive landscape for analyzing TM, especially the TM-related mechanisms and TM-based treatment in cancer.}, }
@article {pmid39084197, year = {2024}, author = {Zhang, Y and Wang, S and Wang, H and Cao, M and Wang, M and Zhang, B and Xiao, C and Zhu, H and Du, S}, title = {Efficacy of Donor-Recipient-Matched Faecal Microbiota Transplantation in Patients with IBS-D: A Single-Centre, Randomized, Double-Blind Placebo-Controlled Study.}, journal = {Digestion}, volume = {105}, number = {6}, pages = {457-467}, doi = {10.1159/000540420}, pmid = {39084197}, issn = {1421-9867}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Female ; Male ; *Irritable Bowel Syndrome/therapy/microbiology ; Adult ; *Gastrointestinal Microbiome ; Double-Blind Method ; Middle Aged ; *Quality of Life ; Treatment Outcome ; *Feces/microbiology ; Diarrhea/therapy/microbiology ; Surveys and Questionnaires ; Tissue Donors/statistics &amp; numerical data ; Young Adult ; }, abstract = {INTRODUCTION: The imbalance in gut microbiota is contributing to the development and progression of IBS. FMT can improve the gut microbiota, and donor-recipient-matched FMT can help develop individualized treatment plans according to different enterotypes. This study aimed to explore the efficacy of donor-recipient-matched FMT in IBS with predominant diarrhoea (IBS-D) and evaluate its effects on gut microbiota.<br><br>METHODS: Twenty-seven patients with IBS-D were randomly divided into donor-recipient-matched FMT group (group P), random-donor FMT group (group R), and placebo group (group B). All participants received corresponding FMT treatment after filling in IBS-S, IBS-QoL, GSRS, and HADS questionnaires and having their stool samples collected at 4, 8, and 12 weeks after treatment. The improvement in the symptoms and the changes in the bacterial flora were analysed for three groups.<br><br>RESULTS: The IBS-SSS, IBS-QoL, GSRS, and anxiety scores of group P were significantly lower after treatment (p < 0.05). The IBS-QoL scores of group R were significantly lower after treatment (p < 0.05). Beta diversity analysis showed that the gut microbiota of group P had an obvious trend of classification after treatment. Seven bacterial genera were related to the differences in the IBS-SSS scores before and after treatment.<br><br>CONCLUSION: Donor-recipient-matched FMT significantly improved the clinical symptoms, quality of life, and anxiety scores of the patients with IBS-D than random-donor FMT.}, }
@article {pmid39084184, year = {2024}, author = {Zhou, SK and Xu, JD and Gao, XQ and Zhang, RJ and Cheng, FF and Yao, WF and Zhang, Y and Geng, T and Zhang, L}, title = {Fructus Jujubae cooperated with water-expelling members in Shizao decoction alleviated intestinal injury and malignant ascites by modulating gut microbiota and metabolic homeostasis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {133}, number = {}, pages = {155895}, doi = {10.1016/j.phymed.2024.155895}, pmid = {39084184}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Drugs, Chinese Herbal/pharmacology ; Male ; *Ascites ; *Rats, Sprague-Dawley ; Homeostasis/drug effects ; Rats ; Euphorbia/chemistry ; Ziziphus/chemistry ; Intestines/drug effects ; Oxidative Stress/drug effects ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {BACKGROUND: Shizao decoction (SZD) consisted of Euphorbia kansui (EK), Euphorbia pekinensis (EP), Daphne genkwa (DG), and Fructus Jujubae (FJ) is a classic Chinese herbal medicine formula for treating malignant ascites, which is closely related to the modulation of gut microbiota by our previous study. For water-expelling members (WEM) including EK, EP, and DG may have side effects on the intestine, FJ is employed for detoxification and effectivity enhancement of WEM. However, the underlying mechanism for the compatibility of WEM and FJ is still unknown.<br><br>PURPOSE: To investigate the effect of the compatibility of WEM with FJ in SZD on malignant ascites and elucidate the potential mechanism from the perspective of the modulation of gut microbiota and related metabolic function.<br><br>METHODS: Qualitative and quantitative evaluation of main components was conducted for comprehensive characterization of SZD and WEM. The effect of WEM and SZD was compared on malignant ascites effusion (MAE) rats. The intestinal injury was evaluated by HE staining and oxidative damage. Ascites weight, urine amount, fecal water content, the expression of aquaporins, and cytokines in ascites (IL-6, VEGF, and TNF-&#x3b1;) were measured to estimate the water-expelling activity. The intestinal flora was detected by 16S rDNA sequencing and the content of fecal short-chain fatty acids (SCFAs) was analyzed using gas chromatography-mass spectrometry. Pseudo-germ-free (PGF) and fecal bacteria transplantation animal experiments were subsequently employed to validate this finding. The fecal metabolomics and correlation analysis were finally conducted to explore the related metabolic changes.<br><br>RESULTS: 51 and 33 components were identified in SZD and WEM, respectively. Compared to WEM alone, the compatibility with FJ remarkably reduced intestinal oxidative damage in MAE rats. Ascites was also relieved by downregulating the expression of AQP3 in the colon and decreasing the levels of IL-6, TNF-&#x3b1; and VEGF in ascites. The diversity of gut microbiota was reversed with an increase in Lactobacillus and Clostridia_UCG-014 while a decrease in Colidextribacter. Under the PGF condition, compatibility of WEM with FJ failed to reduce intestinal injury and alleviate MA significantly, but this effect was further enhanced after FMT. 23 potential fecal metabolites were finally identified. Correlation analysis further showed that Lactobacillus and Clostridia_UCG-014 were positively correlated with SCFAs and l-tryptophan. Colidextribacter was negatively correlated with thymidine but positively correlated with ursodeoxycholic acid and deoxycholic acid.<br><br>CONCLUSION: FJ cooperated with WEM reduced intestinal injury and alleviated malignant ascites by modulating gut microbiota, short-chain fatty and tryptophan metabolism. These findings provide a scientific basis for the clinical application of FJ from SZD and the safe usage of SZD.}, }
@article {pmid39083099, year = {2024}, author = {Heiss, MM and Lange, J and Knievel, J and Yohannes, A and Hügle, U and Dormann, AJ and Eisenberger, CF}, title = {Treatment of anastomotic leak in colorectal surgery by endoluminal vacuum therapy with the VACStent avoiding a stoma - a pilot study.}, journal = {Langenbeck's archives of surgery}, volume = {409}, number = {1}, pages = {234}, pmid = {39083099}, issn = {1435-2451}, mesh = {Humans ; Pilot Projects ; *Anastomotic Leak/prevention &amp; control ; Female ; Male ; Middle Aged ; Aged ; Surgical Stomas/adverse effects ; Negative-Pressure Wound Therapy ; Treatment Outcome ; Anastomosis, Surgical/adverse effects ; Aged, 80 and over ; Adult ; }, abstract = {PURPOSE: Anastomotic leak (AL) represents the most relevant and devastating complication in colorectal surgery. Endoscopic vacuum therapy (EVT) using the VACStent is regarded as a significant improvement in the treatment of upper gastrointestinal wall defects. The innovative concept of the VACStent was transferred to the lower GI tract, gaining initial experience by investigating safety and efficacy in 12 patients undergoing colorectal resections.<br><br>METHODS: The pilot study, as part of a German registry, began with 2 patients suffering from AL, who were treated with the VACStent after stoma placement. Subsequently, 6 patients with AL were treated with the VACStent omitting a stoma placement, with a focus on fecal passage and wound healing. Finally, the preemptive anastomotic coverage was investigated in 4 patients with high-risk anastomoses to avoid prophylactic stoma placement.<br><br>RESULTS: In total 26 VACStents were placed without problems. The conditioning and drainage function were maintained, and no clogging problems of the sponge cylinder were observed. No relevant clinical VACStent-associated complications were observed; however, in 2 patients, a dislodgement of a VACStent occurred. The 6 patients with AL but without stoma had a median treatment with 3 VACStents per case with a laytime of 17 days, leading to complete wound healing in all cases. The 4 prophylactic VACStent applications were without complications.<br><br>CONCLUSION: The clinical application of the VACStent in the lower GI tract shows that successful treatment of anastomotic colonic leaks and avoidance of creation of an anus praeter is possible.<br><br>TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT04884334, date of registration 2021-05-04, retrospectively registered.}, }
@article {pmid39081882, year = {2024}, author = {Sun, M and Lu, F and Yu, D and Wang, Y and Chen, P and Liu, S}, title = {Respiratory diseases and gut microbiota: relevance, pathogenesis, and treatment.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1358597}, pmid = {39081882}, issn = {1664-302X}, abstract = {Preclinical evidence has firmly established a bidirectional interaction among the lung, gut, and gut microbiome. There are many complex communication pathways between the lung and intestine, which affect each other's balance. Some metabolites produced by intestinal microorganisms, intestinal immune cells, and immune factors enter lung tissue through blood circulation and participate in lung immune function. Altered gut-lung-microbiome interactions have been identified in rodent models and humans of several lung diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, asthma, etc. Emerging evidence suggests that microbial therapies can prevent and treat respiratory diseases, but it is unclear whether this association is a simple correlation with the pathological mechanisms of the disease or the result of causation. In this review, we summarize the complex and critical link between the gut microbiota and the lung, as well as the influence and mechanism of the gut microbiota on respiratory diseases, and discuss the role of interventions such as prebiotics and fecal bacteria transplantation on respiratory diseases. To provide a reference for the rational design of large-scale clinical studies, the direct application of microbial therapy to respiratory-related diseases can reduce the incidence and severity of diseases and accompanying complications.}, }
@article {pmid39081300, year = {2024}, author = {Zaidi, SMH and Haider, R and Kazmi, SAB and Husnain, A and Khan, S and Merchant, S and Tayyab, H and Wazeen, FR and Chaudhary, AJ}, title = {Beyond Antibiotics: Novel Approaches in the Treatment of Recurrent Clostridioides difficile Infection.}, journal = {ACG case reports journal}, volume = {11}, number = {8}, pages = {e01333}, pmid = {39081300}, issn = {2326-3253}, }
@article {pmid39079886, year = {2024}, author = {Pedreira-Robles, G and Bach-Pascual, A and Collado-Nieto, S and Padilla, E and Burballa, C and Arias-Cabrales, C and Redondo-Pachón, D and Sánchez, F and Horcajada, JP and Pascual, J and Crespo, M and Villar-García, J and Pérez-Sáez, MJ}, title = {Screening for tropical and imported infections in migrant kidney transplant candidates from the kidney transplant access consultation.}, journal = {Nefrologia}, volume = {44}, number = {4}, pages = {549-559}, doi = {10.1016/j.nefroe.2024.07.006}, pmid = {39079886}, issn = {2013-2514}, mesh = {Humans ; *Kidney Transplantation ; Cross-Sectional Studies ; Male ; Female ; Middle Aged ; Adult ; Communicable Diseases, Imported/epidemiology/diagnosis ; Prevalence ; Transients and Migrants/statistics &amp; numerical data ; Mass Screening ; Referral and Consultation/statistics &amp; numerical data ; Strongyloidiasis/diagnosis/epidemiology ; }, abstract = {BACKGROUND AND OBJECTIVE: Kidney transplantation (KT) should be postponed in those people with active bacterial, fungal, viral and parasitic processes, since these must be treated and resolved previously. The objective of this study is to present the screening circuit implemented by the Nephrology clinic and describe the prevalence of tropical and imported infections in KT candidates born or coming from endemic areas.<br><br>MATERIALS AND METHODS: Descriptive cross-sectional study, carried out in 2021. Sociodemographic and clinical variables, serological data of general infections and specific tests of tropical infectious diseases were collected. A descriptive analysis of the data was carried out.<br><br>RESULTS: 67 TR candidates from Latin America (32.8%), North Africa (22.4%), Sub-Saharan Africa (14.9%) and Asia (29.9%) were included. 68.7% were men and the mean age was 48.9&#x202f;&#xb1;&#x202f;13.5 years. After the general and specific studies, 42 (62.7%) patients were referred to the Infectious Diseases Service to complete this study or indicate treatment. 35.8% of the patients had eosinophilia, and in one case parasites were detected in feces at the time of the study. Serology for strongyloidiasis was positive in 18 (26.9%) cases, while positive serology for other tropical infections was hardly detected. 34.3% of patients had latent tuberculosis infection.<br><br>CONCLUSIONS: The prevalence of tropical and imported infections in migrant candidates for RT was low, except for strongyloidiasis and latent tuberculosis infection. Its detection and treatment are essential to avoid serious complications in post-TR. To this end, the implementation of an interdisciplinary screening program from the KT access consultation is feasible, necessary and useful.}, }
@article {pmid39079826, year = {2024}, author = {Wu, Q and Yang, LS and Huang, HL and Li, YF and Zhou, YJ and Xu, HM}, title = {Washed microbiota transplantation combined with biological agents promotes histological remission in refractory severe ulcerative colitis with recurrent intestinal infection: A case report.}, journal = {Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology}, volume = {25}, number = {4}, pages = {448-454}, doi = {10.1016/j.ajg.2024.07.008}, pmid = {39079826}, issn = {2090-2387}, mesh = {Humans ; Female ; Adult ; *Colitis, Ulcerative/complications/therapy ; *Fecal Microbiota Transplantation/methods ; *Recurrence ; Antibodies, Monoclonal, Humanized/therapeutic use ; Cytomegalovirus Infections/complications/therapy ; Clostridium Infections/therapy/complications ; Combined Modality Therapy ; Remission Induction ; Gastrointestinal Agents/therapeutic use ; }, abstract = {Ulcerative colitis (UC) is a chronic non-specific colitis disease. In recent years, fecal microbiota transplantation (FMT), including improved washed microbiota transplantation (WMT), and biological agents have helped improve the prognosis of patients with UC. However, a significant number of patients with moderate to severe UC do not get relief from glucocorticoids, immunosuppressants, and TNF-α antagonists. Patients with severe UC are frequently burdened with opportunistic infections and subsequent surgical interventions. Combined treatment modalities are crucial for patients with severe UC and opportunistic infections. Herein, we reported a case of a 25-year-old female with refractory severe UC complicated with recurrent Clostridioides difficile infection and recurrent cytomegalovirus infection for six years. Surgical removal of the affected bowel segment was almost unavoidable. She showed endoscopic and histological recovery after comprehensive WMT and Vedolizumab treatment. The following are our learnings from the case: 1. A combination of WMT and biological agents can potentially obviate the necessity for surgical treatment in patients with refractory severe UC and promote histological remission. 2. Personalized comprehensive treatment and chronic disease management models for patients with UC should be emphasized. 3. WMT can help treat opportunistic infections, which may also strengthen the treatment with gut-targeted biological agents when traditional TNF-α antagonists show poor efficacy.}, }
@article {pmid39078661, year = {2024}, author = {Kou, RW and Li, ZQ and Wang, JL and Jiang, SQ and Zhang, RJ and He, YQ and Xia, B and Gao, JM}, title = {Ganoderic Acid A Mitigates Inflammatory Bowel Disease through Modulation of AhR Activity by Microbial Tryptophan Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {32}, pages = {17912-17923}, doi = {10.1021/acs.jafc.4c01166}, pmid = {39078661}, issn = {1520-5118}, mesh = {Animals ; Humans ; Male ; Mice ; Bacteria/classification/metabolism/genetics/isolation &amp; purification/drug effects ; Disease Models, Animal ; *Gastrointestinal Microbiome/drug effects ; Heptanoic Acids ; *Inflammatory Bowel Diseases/metabolism/drug therapy/microbiology ; Interleukin-22 ; *Lanosterol/analogs &amp; derivatives/pharmacology ; Mice, Inbred C57BL ; *Receptors, Aryl Hydrocarbon/metabolism/genetics ; *Tryptophan/metabolism ; }, abstract = {Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex gastrointestinal condition influenced by genetic, microbial, and environmental factors, among which the gut microbiota plays a crucial role and has emerged as a potential therapeutic target. Ganoderic acid A (GAA), which is a lanostane triterpenoid compound derived from edible mushroom Ganoderma lucidum, has demonstrated the ability to modulate gut dysbiosis. Thus, we investigated the impact of GAA on IBD using a dextran sodium sulfate (DSS)-induced colitis mouse model. GAA effectively prevented colitis, preserved epithelial and mucus layer integrity, and modulated the gut microbiota. In addition, GAA promoted tryptophan metabolism, especially 3-IAld generation, activated the aryl hydrocarbon receptor (AhR), and induced IL-22 production. Fecal microbiota transplantation validated the mediating role of the gut microbiota in the IBD protection conferred by GAA. Our study suggests that GAA holds potential as a nutritional intervention for ameliorating IBD by influencing the gut microbiota, thereby regulating tryptophan metabolism, enhancing AhR activity, and ultimately improving gut barrier function.}, }
@article {pmid39078050, year = {2024}, author = {Lee, PJ and Hung, CM and Yang, AJ and Hou, CY and Chou, HW and Chang, YC and Chu, WC and Huang, WY and Kuo, WC and Yang, CC and Lin, KI and Hung, KH and Chang, LC and Lee, KY and Kuo, HP and Lu, KM and Lai, HC and Kuo, ML and Chen, WJ}, title = {MS-20 enhances the gut microbiota-associated antitumor effects of anti-PD1 antibody.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2380061}, pmid = {39078050}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Animals ; Mice ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology/metabolism ; Humans ; *Tumor Microenvironment/immunology ; *CD8-Positive T-Lymphocytes/immunology ; Fecal Microbiota Transplantation ; Cell Line, Tumor ; Probiotics/administration &amp; dosage/pharmacology ; Immunotherapy ; Female ; Colonic Neoplasms/immunology/therapy/drug therapy/microbiology ; Immune Checkpoint Inhibitors/pharmacology ; Lung Neoplasms/immunology/drug therapy/therapy ; Mice, Inbred BALB C ; Xenograft Model Antitumor Assays ; }, abstract = {Cancer immunotherapy has been regarded as a promising strategy for cancer therapy by blocking immune checkpoints and evoking immunity to fight cancer, but its efficacy seems to be heterogeneous among patients. Manipulating the gut microbiota is a potential strategy for enhancing the efficacy of immunotherapy. Here, we report that MS-20, also known as "Symbiota®", a postbiotic that comprises abundant microbial metabolites generated from a soybean-based medium fermented with multiple strains of probiotics and yeast, inhibited colon and lung cancer growth in combination with an anti-programmed cell death 1 (PD1) antibody in xenograft mouse models. Mechanistically, MS-20 remodeled the immunological tumor microenvironment by increasing effector CD8[+] T cells and downregulating PD1 expression, which were mediated by the gut microbiota. Fecal microbiota transplantation (FMT) from mice receiving MS-20 treatment to recipient mice increased CD8[+] T-cell infiltration into the tumor microenvironment and significantly improved antitumor activity when combined with anti-PD1 therapy. Notably, the abundance of Ruminococcus bromii, which increased following MS-20 treatment, was positively associated with a reduced tumor burden and CD8[+] T-cell infiltration in vivo. Furthermore, an ex vivo study revealed that MS-20 could alter the composition of the microbiota in cancer patients, resulting in distinct metabolic pathways associated with favorable responses to immunotherapy. Overall, MS-20 could act as a promising adjuvant agent for enhancing the efficacy of immune checkpoint-mediated antitumor therapy.}, }
@article {pmid39073834, year = {2024}, author = {Scheperjans, F and Levo, R and Bosch, B and Lääperi, M and Pereira, PAB and Smolander, OP and Aho, VTE and Vetkas, N and Toivio, L and Kainulainen, V and Fedorova, TD and Lahtinen, P and Ortiz, R and Kaasinen, V and Satokari, R and Arkkila, P}, title = {Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial.}, journal = {JAMA neurology}, volume = {81}, number = {9}, pages = {925-938}, pmid = {39073834}, issn = {2168-6157}, mesh = {Humans ; *Parkinson Disease/therapy ; Middle Aged ; Male ; *Fecal Microbiota Transplantation/methods ; Female ; Aged ; Double-Blind Method ; Adult ; Treatment Outcome ; Dysbiosis/therapy ; }, abstract = {IMPORTANCE: Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models.<br><br>OBJECTIVE: To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT.<br><br>This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn &amp; Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis.<br><br>INTERVENTION: Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy.<br><br>MAIN OUTCOMES AND MEASURES: The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs).<br><br>RESULTS: The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P&#x2009;=&#x2009;.75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P&#x2009;=&#x2009;.003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group.<br><br>CONCLUSIONS AND RELEVANCE: FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04854291.}, }
@article {pmid39073794, year = {2024}, author = {Sampson, TR}, title = {Fecal Microbiome Transplants For Parkinson Disease.}, journal = {JAMA neurology}, volume = {81}, number = {9}, pages = {911-913}, doi = {10.1001/jamaneurol.2024.2293}, pmid = {39073794}, issn = {2168-6157}, mesh = {*Parkinson Disease/microbiology/therapy ; Humans ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; }, }
@article {pmid39073205, year = {2024}, author = {Zu, M and Liu, G and Xu, H and Zhu, Z and Zhen, J and Li, B and Shi, X and Shahbazi, MA and Reis, RL and Kundu, SC and Nie, G and Xiao, B}, title = {Extracellular Vesicles from Nanomedicine-Trained Intestinal Microbiota Substitute for Fecal Microbiota Transplant in Treating Ulcerative Colitis.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {36}, number = {41}, pages = {e2409138}, doi = {10.1002/adma.202409138}, pmid = {39073205}, issn = {1521-4095}, support = {82072060//National Natural Science Foundation of China/ ; 82360110//National Natural Science Foundation of China/ ; SWU-XDPY22006//Fundamental Research Funds for the Central Universities/ ; SWU-KQ22075//Fundamental Research Funds for the Central Universities/ ; 2205012980212766//Venture &amp; Innovation Support Program for Chongqing Overseas Returnees/ ; 2022NSCQ-JQX5279//Science Fund for Distinguished Young Scholars of Chongqing Municipality/ ; 20212BDH81019//Key Science and Technology Research Project in Jiangxi Province Department of Education/ ; 20224BAB206073//Key Science and Technology Research Project in Jiangxi Province Department of Education/ ; }, mesh = {Animals ; *Colitis, Ulcerative/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Mice ; *Extracellular Vesicles/chemistry/metabolism ; *Nanomedicine/methods ; *Curcumin/chemistry ; Nanoparticles/chemistry ; Colon/microbiology/metabolism ; Mice, Inbred C57BL ; Tea/chemistry ; }, abstract = {The biosafety concerns associated with fecal microbiota transplant (FMT) limit their clinical application in treating ulcerative colitis (UC). Gut microbiota secrete abundant extracellular vesicles (Gm-EVs), which play a critical role in bacteria-to-bacteria and bacteria-to-host communications. Herein, intestinal microbiota are trained using tea leaf lipid/pluronic F127-coated curcumin nanocrystals (CN@Lp127s), which can maintain stability during transit through the gastrointestinal tract. Compared with FMT, Gm-EVs derived from healthy mice significantly improve treatment outcomes against UC by reducing colonic inflammatory responses, restoring colonic barrier function, and rebalancing intestinal microbiota. Strikingly, Gm-EVs obtained from CN@Lp127-trained healthy mice exhibit a superior therapeutic effect on UC compared to groups receiving FMT from healthy mice, Gm-EVs from healthy mice, and FMT from CN@Lp127-trained healthy mice. Oral administration of Gm-EVs from CN@Lp127-trained healthy mice not only alleviates colonic inflammation, promotes mucosal repair, and regulates gut microbiota but also regulates purine metabolism to decrease the uric acid level, resulting in a robust improvement in the UC. This study demonstrates the UC therapeutic efficacy of Gm-EVs derived from nanomedicine-trained gut microbiota in regulating the immune microenvironment, microbiota, and purine metabolism of the colon. These EVs provide an alternative platform to replace FMT as a treatment for UC.}, }
@article {pmid39071723, year = {2024}, author = {Huang, C and Huang, C and Tian, R and Pu, Y and Chen, P}, title = {Washed microbiota transplantation via colonic transendoscopic enteral tube rescues severe acute pancreatitis: A case series.}, journal = {Heliyon}, volume = {10}, number = {13}, pages = {e33678}, pmid = {39071723}, issn = {2405-8440}, abstract = {BACKGROUND: Gut microbiota dysbiosis plays a significant role in the development of acute pancreatitis (AP). However, a recent randomized trial reported negative findings regarding the use of fecal microbiota transplantation (FMT) via the mid-gut tube in severe AP. The case series presents the feasibility of washed microbiota transplantation (WMT) as a new methodology of FMT and its delivery via colonic transendoscopic enteral tubing (TET) for severe AP.<br><br>CASE SERIES: We presented two cases of severe AP rapidly rescued using WMT via colonic TET. Symptoms related to severe AP and the acute physiology and chronic health evaluation-II score improved soon after WMT. In Case 1, bilirubin and infection indexes continuously decreased after the initial WMT and the patient was successfully weaned off the ventilator and recovered from multiple organ system failures (MSOF) within ten days. In Case 2, the patient's consciousness rapidly improved within one day after WMT, with normal bowel sounds and stable blood pressure without vasoactive drug maintenance. Both Case 1 and Case 2 completed follow-ups of seven months and twenty-two months, respectively, with no reports of new-onset diabetes.<br><br>CONCLUSION: WMT via colonic TET played a critical therapeutic role in rescuing severe AP cases. This is the first report providing direct evidence for the clinical value of targeting microbiota through colonic TET in rescuing severe AP.}, }
@article {pmid39071345, year = {2024}, author = {Debray, R and Dickson, CC and Webb, SE and Archie, EA and Tung, J}, title = {Shared environments complicate the use of strain-resolved metagenomics to infer microbiome transmission.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39071345}, issn = {2692-8205}, support = {R01 AG071684/AG/NIA NIH HHS/United States ; R01 AG075914/AG/NIA NIH HHS/United States ; R61 AG078470/AG/NIA NIH HHS/United States ; }, abstract = {In humans and other social animals, social partners have more similar microbiomes than expected by chance, suggesting that social contact transfers microorganisms. Yet, social microbiome transmission can be difficult to identify based on compositional data alone. To overcome this challenge, recent studies have used information about microbial strain sharing (i.e., the shared presence of highly similar microbial sequences) to infer transmission. However, the degree to which strain sharing is influenced by shared traits and environments among social partners, rather than transmission per se, is not well understood. Here, we first use a fecal microbiota transplant dataset to show that strain sharing can recapitulate true transmission networks under ideal settings when donor-recipient pairs are unambiguous and recipients are sampled shortly after transmission. In contrast, in gut metagenomes from a wild baboon population, we find that demographic and environmental factors can override signals of strain sharing among social partners. We conclude that strain-level analyses provide useful information about microbiome similarity, but other facets of study design, especially longitudinal sampling and careful consideration of host characteristics, are essential for inferring the underlying mechanisms.}, }
@article {pmid39071049, year = {2024}, author = {Ramos-Martínez, A and Múñez, E and Del-Campo, R and Nieto-Fernández, A and Gonzalez-Haba, M and Calderón-Parra, J}, title = {Fecal microbiota transplantation as a preventive treatment for recurrent acute cholangitis.}, journal = {IDCases}, volume = {37}, number = {}, pages = {e02025}, pmid = {39071049}, issn = {2214-2509}, abstract = {BACKGROUND: Recurrent acute cholangitis (RAC) is a relatively uncommon entity that presents significant management difficulties. We present the case of a patient with RAC in whom the number of episodes was reduced after a novel therapeutic procedure.<br><br>CASE REPORT: A 93-year-old male who in June 2019 was admitted for chills without fever, shivering, epigastric abdominal pain and moderate jaundice. Both abdominal ultrasound and CT scan showed intrahepatic and extrahepatic duct dilatation up to the papilla with no evidence of mass at that level. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and abundant biliary sludge was removed. E. coli was identified as the cause of several of the episodes. Some isolates were shown to produce extended spectrum beta-lactamase (ESBL). Papillotomy was performed and plastic prosthesis and later a metallic prosthesis were implanted. Several months later a surgical bypass of the biliary tract was performed due to persistent episodes of cholangitis. When the chronic suppressive antibiotic treatment subsequently instituted to prevent new episodes of cholangitis failed, it was decided to perform a fecal microbiota transplant from a healthy donor and to suspend the chronic suppressive treatment. Since then, she has not presented new episodes of RAC for more than 10 months of clinical follow-up. BLEE-producing E. coli in the gastrointestinal tract could not be eradicated.<br><br>COMMENT: Chronic colonization of the biliary tract by certain enterobacteria such as E. coli has been identified as a relevant pathogenic factor in cases of RAC. FMT may be a promising tool to improve the clinical course of patients with RAC.}, }
@article {pmid39070844, year = {2024}, author = {Zhang, JT and Zhang, N and Dong, XT and Wang, XR and Ma, HW and Liu, YD and Li, MR}, title = {Efficacy and safety of fecal microbiota transplantation for treatment of ulcerative colitis: A post-consensus systematic review and meta-analysis.}, journal = {World journal of clinical cases}, volume = {12}, number = {21}, pages = {4691-4702}, pmid = {39070844}, issn = {2307-8960}, abstract = {BACKGROUND: Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation (FMT) as a therapy for ulcerative colitis (UC). However, the treatment processes and outcomes of these studies vary.<br><br>AIM: To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis.<br><br>METHODS: The inclusion criteria involved reports of adult patients with UC treated with FMT, while studies that did not report clinical outcomes or that included patients with infection were excluded. Clinical remission (CR) and endoscopic remission (ER) were the primary and secondary outcomes, respectively.<br><br>RESULTS: We included nine studies retrieved from five electronic databases. The FMT group had better CR than the control group [relative risk (RR) = 1.53; 95% confidence interval (CI): 1.19-1.94; P < 0.0008]. ER was statistically significantly different between the two groups (RR = 2.80; 95%CI: 1.93-4.05; P < 0.00001). Adverse events did not differ significantly between the two groups.<br><br>CONCLUSION: FMT demonstrates favorable performance and safety; however, well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended. Furthermore, standardizing the FMT process is urgently needed for improved safety and efficacy.}, }
@article {pmid39065063, year = {2024}, author = {Bottino, P and Vay, D and Leli, C and Ferrara, L and Pizzo, V and Gotta, F and Raiteri, A and Rapallo, F and Roveta, A and Maconi, A and Rocchetti, A}, title = {Evaluation of Bacterial Viability for Fecal Microbiota Transplantation: Impact of Thawing Temperature and Storage Time.}, journal = {Microorganisms}, volume = {12}, number = {7}, pages = {}, pmid = {39065063}, issn = {2076-2607}, abstract = {Fecal Microbiota Transplantation (FMT) represents a promising therapeutic tool under study for several purposes and is currently applied to the treatment of recurrent Clostridioides difficile infection. However, since the use of fresh stool was affected by several issues linked to donor screening, the development of a frozen stool bank is a reliable option to standardize FMT procedures. Nevertheless, different environmental factors impact microbial viability. Herein, we report the effect of different thawing temperatures and storage conditions on bacterial suspensions in the FMT procedure. In total, 20 stool samples were divided into aliquots and tested across a combination of different storing periods (15, 30; 90 days) and thawing procedures (4 °C overnight, room temperature for 1 h; 37 °C for 5 min). Focusing on storage time, our data showed a significant reduction in viability for aerobic and anaerobic bacteria after thawing for 15 days, while no further reductions were observed until after 90 days. Instead, among the different thawing procedures, no significant differences were observed for aerobic bacteria, while for anaerobes, thawing at 37 °C for 5 min was more effective in preserving the bacterial viability. In conclusion, the frozen fecal microbiota remained viable for at least three months, with an excellent recovery rate in all three thawing conditions.}, }
@article {pmid39064809, year = {2024}, author = {Kuźniar, J and Kozubek, P and Czaja, M and Leszek, J}, title = {Correlation between Alzheimer's Disease and Gastrointestinal Tract Disorders.}, journal = {Nutrients}, volume = {16}, number = {14}, pages = {}, pmid = {39064809}, issn = {2072-6643}, mesh = {Humans ; *Alzheimer Disease/microbiology ; *Gastrointestinal Microbiome ; *Gastrointestinal Diseases/microbiology ; Brain-Gut Axis/physiology ; Helicobacter Infections/complications/microbiology ; Periodontitis/microbiology ; Gastrointestinal Tract/microbiology/metabolism ; Helicobacter pylori ; Inflammatory Bowel Diseases/microbiology/metabolism ; Brain/metabolism ; }, abstract = {Alzheimer's disease is the most common cause of dementia globally. The pathogenesis is multifactorial and includes deposition of amyloid-β in the central nervous system, presence of intraneuronal neurofibrillary tangles and a decreased amount of synapses. It remains uncertain what causes the progression of the disease. Nowadays, it is suggested that the brain is connected to the gastrointestinal tract, especially the enteric nervous system and gut microbiome. Studies have found a positive association between AD and gastrointestinal diseases such as periodontitis, Helicobacter pylori infection, inflammatory bowel disease and microbiome disorders. H. pylori and its metabolites can enter the CNS via the oropharyngeal olfactory pathway and may predispose to the onset and progression of AD. Periodontitis may cause systemic inflammation of low severity with high levels of pro-inflammatory cytokines and neutrophils. Moreover, lipopolysaccharide from oral bacteria accompanies beta-amyloid in plaques that form in the brain. Increased intestinal permeability in IBS leads to neuronal inflammation from transference. Chronic inflammation may lead to beta-amyloid plaque formation in the intestinal tract that spreads to the brain via the vagus nerve. The microbiome plays an important role in many bodily functions, such as nutrient absorption and vitamin production, but it is also an important factor in the development of many diseases, including Alzheimer's disease. Both the quantity and diversity of the microbiome change significantly in patients with AD and even in people in the preclinical stage of the disease, when symptoms are not yet present. The microbiome influences the functioning of the central nervous system through, among other things, the microbiota-gut-brain axis. Given the involvement of the microbiome in the pathogenesis of AD, antibiotic therapy, probiotics and prebiotics, and faecal transplantation are being considered as possible therapeutic options.}, }
@article {pmid39064789, year = {2024}, author = {Liu, W and Xu, S and Zhang, B and Sun, X}, title = {Ramulus Mori (Sangzhi) Alkaloids Alleviate Diabetic Nephropathy through Improving Gut Microbiota Disorder.}, journal = {Nutrients}, volume = {16}, number = {14}, pages = {}, pmid = {39064789}, issn = {2072-6643}, support = {82274174//the National Natural Science Foundation of China/ ; No. 2022-I2M-1-018//the CAMS Innovation Fund for Medical Sciences (CIFMS)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diabetic Nephropathies/drug therapy ; *Alkaloids/pharmacology ; Mice ; Male ; *Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; Podocytes/drug effects ; Diabetes Mellitus, Experimental/drug therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Diabetic nephropathy (DN), one of the leading causes of end-stage kidney failure worldwide, is closely associated with high mortality in diabetic patients. However, therapeutic drugs for DN are still lacking. Ramulus Mori alkaloids (SZ-A), an effective component of alkaloids extracted from Ramulus Mori, have been found to improve glucose and lipid metabolism to mitigate diabetes and obesity; however, few studies have focused on their effects on DN progression. Thus, we investigated the protective role of SZ-A on DN through 16S rRNA sequencing, non-targeted metabolomics, and fecal microbiota transplantation (FMT) experiments. To address our hypothesis, we established the DN mouse model by combining a high-fat diet (HFD) with streptozotocin (STZ) injection. Herein, we demonstrated that SZ-A supplementation was recalcitrant to renal injury in DN mice, improving glomerular morphology, reversing the blood biochemistry parameters, and ameliorating podocyte injury. Importantly, the composition of the gut microbiota altered after SZ-A treatment, especially with the elevated abundance of Dubosiella and the increased level of serum pentadecanoic acid. FMT experiments further revealed that the gut microbiota exerted critical effects in mediating the beneficial roles of SZ-A. In vitro experiments proved that pentadecanoic acid administration improved podocyte apoptosis induced by AGEs. Taken together, SZ-A play a renoprotective role, possibly through regulating the gut microbiota and promoting pentadecanoic acid production. Our current study lends support to more extensive clinical applications of SZ-A.}, }
@article {pmid39063080, year = {2024}, author = {Zhang, Y and Wang, C and Lang, H and Yu, H and Zhou, M and Rao, X and Zhang, Q and Yi, L and Zhu, J and Mi, M}, title = {The Contrasting Effects of Two Distinct Exercise Training Modalities on Exhaustive Exercise-Induced Muscle Damage in Mice May Be Associated with Alterations in the Gut Microbiota.}, journal = {International journal of molecular sciences}, volume = {25}, number = {14}, pages = {}, pmid = {39063080}, issn = {1422-0067}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Physical Conditioning, Animal ; Mice ; *Muscle, Skeletal/metabolism ; *Fatty Acids, Volatile/metabolism ; Male ; Oxidative Stress ; Mice, Inbred C57BL ; Swimming ; }, abstract = {Exhaustive exercise is known to induce muscle damage characterized by inflammation and oxidative stress. Although "regular" and "weekend warrior" exercise regimens have been shown to confer comparable health benefits in human studies, such as reduced risks of all-cause, cardiovascular disease (CVD), and cancer mortality, their differential impacts on muscle damage post-exhaustive exercise remain unclear. This study aimed to compare the effects of long-term, moderate-intensity (LTMI) and short-term, high-intensity (STHI) training modalities, matched for total exercise volume, on gut microbiota, short-chain fatty acids (SCFAs), and exhaustive exercise-induced muscle damage in mice, as well as to evaluate the correlation between these factors. LTMI is considered a regular exercise regimen, while STHI shares some similarities with the "weekend warrior" pattern, such as promoting exercise intensity and condensing training sessions into a short period. Our findings indicate that LTMI training significantly enhanced the abundance of SCFA-producing bacteria, including Akkermansia, Prevotellaceae_NK3B31_group, Odoribacter, Alistipes, and Lactobacillus, thereby increasing SCFA levels and attenuating muscle damage following exhaustive swimming. In contrast, STHI training increased the abundance of opportunistic pathogens such as Staphylococcus and Bilophila, without altering SCFA levels, and was associated with exacerbated muscle damage. Moreover, we observed a significant negative correlation between the abundance of SCFA-producing bacteria and SCFA levels with the expression of inflammatory cytokines in the muscle of mice post-exhaustive exercise. Conversely, the abundance of Staphylococcus and Bilophila showed a notable positive correlation with these cytokines. Additionally, the effects of LTMI and STHI on exhaustive exercise-induced muscle damage were transmissible to untrained mice via fecal microbiota transplantation, suggesting that gut microbiota changes induced by these training modalities may contribute to their contrasting impacts on muscle damage. These results underscore the significance of selecting an appropriate training modality prior to engaging in exhaustive exercise, with implications for athletic training and injury prevention.}, }
@article {pmid39062985, year = {2024}, author = {Sadowski, K and Zając, W and Milanowski, &#x141; and Koziorowski, D and Figura, M}, title = {Exploring Fecal Microbiota Transplantation for Modulating Inflammation in Parkinson's Disease: A Review of Inflammatory Markers and Potential Effects.}, journal = {International journal of molecular sciences}, volume = {25}, number = {14}, pages = {}, pmid = {39062985}, issn = {1422-0067}, mesh = {Humans ; *Parkinson Disease/microbiology/therapy/metabolism ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Animals ; *Biomarkers ; *Inflammation/metabolism/microbiology ; Brain-Gut Axis ; }, abstract = {Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by numerous motor and non-motor symptoms. Recent data highlight a potential interplay between the gut microbiota and the pathophysiology of PD. The degeneration of dopaminergic neurons in PD leads to motor symptoms (tremor, rigidity, and bradykinesia), with antecedent gastrointestinal manifestations, most notably constipation. Consequently, the gut emerges as a plausible modulator in the neurodegenerative progression of PD. Key molecular changes in PD are discussed in the context of the gut-brain axis. Evidence suggests that the alterations in the gut microbiota composition may contribute to gastroenteric inflammation and influence PD symptoms. Disturbances in the levels of inflammatory markers, including tumor necrosis factor-α (TNF α), interleukin -1β (IL-1β), and interleukin-6 (IL-6), have been observed in PD patients. These implicate the involvement of systemic inflammation in disease pathology. Fecal microbiota transplantation emerges as a potential therapeutic strategy for PD. It may mitigate inflammation by restoring gut homeostasis. Preclinical studies in animal models and initial clinical trials have shown promising results. Overall, understanding the interplay between inflammation, the gut microbiota, and PD pathology provides valuable insights into potential therapeutic interventions. This review presents recent data about the bidirectional communication between the gut microbiome and the brain in PD, specifically focusing on the involvement of inflammatory biomarkers.}, }
@article {pmid39062142, year = {2024}, author = {Goloshchapov, OV and Chukhlovin, AB and Polev, DE and Eismont, YA and Bug, DS and Kusakin, AV and Kosarev, OV and Klementeva, RV and Gostev, VV and Ageevets, VA and Volkov, NP and Ipatova, AS and Moiseev, IS and Spiridonova, AA and Sidorenko, SV and Kulagin, AD}, title = {Time-Dependent Shifts in Intestinal Bacteriome, Klebsiella Colonization and Incidence of Antibiotic-Resistance Genes after Allogeneic Hematopoietic Stem Cell Transplantation.}, journal = {Biomedicines}, volume = {12}, number = {7}, pages = {}, pmid = {39062142}, issn = {2227-9059}, support = {22-15-00149//Russian Science Foundation/ ; 22-15-00149//Russian Science Foundation/ ; }, abstract = {Dose-intensive cytostatic therapy and antibiotic treatment in allogeneic hematopoietic stem cell transplantation (allo-HSCT) cause severe abnormalities in a composition of gut microbiota as well as the emergence of antibiotic resistance. The data on the longitudinal recovery of major bacterial phyla and the expansion of genes associated with antibiotic resistance are limited. We collected regular stool samples during the first year after allo-HSCT from 12 adult patients with oncohematological disorders after allo-HSCT and performed 16SrRNA sequencing, multiplex PCR, conventional bacteriology and CHROMagar testing. We observed a decline in Shannon microbiota diversity index as early as day 0 of allo-HSCT (p = 0.034) before any administration of antibiotics, which persisted up to 1 year after transplantation, when the Shannon index returned to pre-transplant levels (p = 0.91). The study confirmed the previously shown decline in Bacillota (Firmicutes) genera and the expansion of E. coli/Shigella, Klebsiella and Enterococci. The recovery of Firmicutes was slower than that of other phyla and occurred only a year post-transplant. A positive correlation was observed between the expansion of E. coli/Shigella genera and blaKPC, blaCTX-M-1 and blaTEM (p < 0.001), Klebsiella spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaTEM, and blaSHV (p < 0.001), Pseudomonas spp. and blaNDM (p = 0.002), Enterococcus spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaSHV (p < 0.01). The correlation was observed between the expansion of Enterobacterales and and carbapenemase-positive CHROMagar samples (p < 0.001). Samples positive for carbapenem-resitant bacteria were at their maximum levels on day +30, and were gradually diminishing one year after allo-HSCT. From day +30 to +60, all isolated K. pneumoniae strains in fecal samples proved to be resistant to the main antibiotic groups (carbapenems, aminoglycosides, fluoroquinolones, third-generation cephalosporins). One year after HSCT, we documented the spontaneous decolonization of K. pneumoniae. The sensitivity of molecular biology techniques in the search for total and antibiotic-resistant Klebsiella seems to be superior to common bacteriological cultures. Future studies should be focused on searching for novel approaches to the efficient reconstitution and/or maintenance of strictly anaerobic microbiota in oncological patients.}, }
@article {pmid39061970, year = {2024}, author = {Chen, JH and Chiu, CH and Chen, CC and Chen, YC and Yeh, PJ and Kuo, CJ and Chiu, CT and Cheng, HT and Pan, YB and Le, PH}, title = {Comparative Efficacy of Fecal Microbiota Transplantation in Treating Refractory or Recurrent Clostridioides difficile Infection among Patients with and without Inflammatory Bowel Disease: A Retrospective Cohort Study.}, journal = {Biomedicines}, volume = {12}, number = {7}, pages = {}, pmid = {39061970}, issn = {2227-9059}, abstract = {Clostridioides difficile infection (CDI) worsens inflammatory bowel disease (IBD) prognosis. While fecal microbiota transplantation (FMT) is effective for refractory or recurrent CDI (rrCDI), comparative success rates between IBD and non-IBD patients are scarce. This study addresses this gap. A retrospective cohort study was conducted at Chang Gung Memorial Hospital from April 2019 to October 2023. Patients receiving FMT for rrCDI were categorized into IBD and non-IBD groups. Baseline characteristics and outcomes were compared at one month and one year, with successful FMT defined as the resolution of diarrhea without CDI recurrence. The study included 88 patients: 30 with IBD and 58 without IBD. The IBD group was younger, with fewer comorbidities. Success rates at one month were similar between groups (IBD: 80.0% vs. non-IBD: 78.9%, p = 0.908), as were negative toxin tests (IBD: 83.3% vs. non-IBD: 63.8%, p = 0.174). One-year success rates (IBD: 70.0% vs. non-IBD: 67.6%, p = 0.857) and eradication rates (IBD: 94.4% vs. non-IBD: 73.9%, p = 0.112) were also similar. Poor bowel preparation predicted FMT failure at one month (OR = 0.23, p = 0.019). No safety issues were reported. FMT is a safe, effective treatment for rrCDI, demonstrating similar success rates in patients with and without IBD.}, }
@article {pmid39061510, year = {2024}, author = {Kiełbik, P and Witkowska-Piłaszewicz, O}, title = {The Relationship between Canine Behavioral Disorders and Gut Microbiome and Future Therapeutic Perspectives.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {14}, pages = {}, pmid = {39061510}, issn = {2076-2615}, abstract = {Canine behavioral disorders have become one of the most common concerns and challenging issues among dog owners. Thus, there is a great demand for knowledge about various factors affecting dogs' emotions and well-being. Among them, the gut-brain axis seems to be particularly interesting, especially since in many instances the standard treatment or behavioral therapies insufficiently improve animal behavior. Therefore, to face this challenge, the search for novel therapeutic methods is highly required. Existing data show that mammals' gut microbiome, immune system, and nervous system are in continuous communication and influence animal physiology and behavior. This review aimed to summarize and discuss the most important scientific evidence on the relationship between mental disorders and gut microbiota in dogs, simultaneously presenting comparable outcomes in humans and rodent models. A comprehensive overview of crucial mechanisms of the gut-brain axis is included. This refers especially to the neurotransmitters crucial for animal behavior, which are regulated by the gut microbiome, and to the main microbial metabolites-short-chain fatty acids (SCFAs). This review presents summarized data on gut dysbiosis in relation to the inflammation process within the organism, as well as the activation of the hypothalamic-pituitary-adrenal (HPA) axis. All of the above mechanisms are presented in this review in strict correlation with brain and/or behavioral changes in the animal. Additionally, according to human and laboratory animal studies, the gut microbiome appears to be altered in individuals with mental disorders; thus, various strategies to manipulate the gut microbiota are implemented. This refers also to the fecal microbiome transplantation (FMT) method, based on transferring the fecal matter from a donor into the gastrointestinal tract of a recipient in order to modulate the gut microbiota. In this review, the possible effects of the FMT procedure on animal behavioral disorders are discussed.}, }
@article {pmid39060829, year = {2025}, author = {Ding, G and Yang, X and Li, Y and Wang, Y and Du, Y and Wang, M and Ye, R and Wang, J and Zhang, Y and Chen, Y and Zhang, Y}, title = {Gut microbiota regulates gut homeostasis, mucosal immunity and influences immune-related diseases.}, journal = {Molecular and cellular biochemistry}, volume = {480}, number = {4}, pages = {1969-1981}, pmid = {39060829}, issn = {1573-4919}, support = {KFJJ-2023-08//Key Laboratory of Anti-inflammatory and Immunological Drugs of the Ministry of Education of the People's Republic of China/ ; 2022KJZD08//Hefei Normal University School-level research project/ ; KJ2021ZD0113&amp; 2022AH052166//Natural Science Foundation of Higher Education in Anhui Province/ ; HXXM2022129&amp; HXXM2023075//Horizontal Development Project of Hefei Normal University/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Homeostasis/immunology ; *Immunity, Mucosal ; Animals ; *Immune System Diseases/microbiology/immunology/therapy ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *Intestinal Mucosa/immunology/microbiology ; }, abstract = {The intestinal microbiome constitutes a sophisticated and massive ecosystem pivotal for maintaining gastrointestinal equilibrium and mucosal immunity via diverse pathways. The gut microbiota is continuously reshaped by multiple environmental factors, thereby influencing overall wellbeing or predisposing individuals to disease state. Many observations reveal an altered microbiome composition in individuals with autoimmune conditions, coupled with shifts in metabolic profiles, which has spurred ongoing development of therapeutic interventions targeting the microbiome. This review delineates the microbial consortia of the intestine, their role in sustaining gastrointestinal stability, the association between the microbiome and immune-mediated pathologies, and therapeutic modalities focused on microbiome modulation. We emphasize the entire role of the intestinal microbiome in human health and recommend microbiome modulation as a viable strategy for disease prophylaxis and management. However, the application of gut microbiota modification for the treatment of immune-related diseases, such as fecal microbiota transplantation and probiotics, remain quite challenging. Therefore, more research is needed into the role and mechanisms of these therapeutics.}, }
@article {pmid39060738, year = {2024}, author = {Levy, EI and Dinleyici, M and Dinleyici, E and Vandenplas, Y}, title = {Clostridioides difficile Infections: Prevention and Treatment Strategies.}, journal = {Advances in experimental medicine and biology}, volume = {1449}, number = {}, pages = {175-186}, pmid = {39060738}, issn = {0065-2598}, mesh = {Humans ; *Clostridium Infections/prevention &amp; control/microbiology/therapy ; *Clostridioides difficile/pathogenicity/physiology ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; *Anti-Bacterial Agents/therapeutic use ; Gastrointestinal Microbiome ; Diarrhea/prevention &amp; control/microbiology/therapy ; }, abstract = {Clostridioides difficile is the most common causative agent of antibiotic-associated diarrhea. This spore forming, obligate anaerobic, gram-positive bacillus is becoming responsible for an increasing number of infections worldwide, both in community and in hospital settings, whose severity can vary widely from an asymptomatic infection to a lethal disease. While discontinuation of antimicrobial agents and antibiotic treatment of the infection remain the cornerstone of therapy, more recent fecal microbiota transplantation has also been valid as a therapy. The use of probiotics, especially Saccharomyces boulardii CNCM I-745 have become valid forms of prevention therapy. Although there are studies in adults with microbiota-targeted new generation therapies and Clostridium difficile vaccines, there are no data in the paediatric age group yet.}, }
@article {pmid39060734, year = {2024}, author = {Nicastro, E and D'Antiga, L}, title = {Nutritional Interventions, Probiotics, Synbiotics and Fecal Microbiota Transplantation in Steatotic Liver Disease : Pediatric Fatty Liver and Probiotics.}, journal = {Advances in experimental medicine and biology}, volume = {1449}, number = {}, pages = {113-133}, pmid = {39060734}, issn = {0065-2598}, mesh = {Humans ; *Probiotics/therapeutic use/administration &amp; dosage ; *Synbiotics/administration &amp; dosage ; Child ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Fatty Liver/therapy/microbiology/pathology ; Non-alcoholic Fatty Liver Disease/microbiology/therapy/metabolism ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major health problem worldwide, and the strongest determinant of liver disease in children. The possible influence of high-fat/low-fiber dietary patterns with microbiota (e.g., increased Firmicutes/Bacteroidetes ratio), and ultimately with MASLD occurrence and progression has been elucidated by several association studies. The possible mechanisms through which microbes exert their detrimental effects on MASLD include gut vascular barrier damage, a shift towards non-tolerogenic immunologic environment, and the detrimental metabolic changes, including a relative reduction of propionate and butyrate in favor of acetate, endogenous ethanol production, and impairment of the unconjugated bile acid-driven FXR-mediated gut-liver axis. The impact of nutritional and probiotic interventions in children with MASLD is described.}, }
@article {pmid39059396, year = {2024}, author = {Kim, Y and Kim, G and Kim, S and Cho, B and Kim, SY and Do, EJ and Bae, DJ and Kim, S and Kweon, MN and Song, JS and Park, SH and Hwang, SW and Kim, MN and Kim, Y and Min, K and Kim, SH and Adams, MD and Lee, C and Park, H and Park, SR}, title = {Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {8}, pages = {1380-1393.e9}, doi = {10.1016/j.chom.2024.06.010}, pmid = {39059396}, issn = {1934-6069}, mesh = {Animals ; Humans ; Mice ; Cytokines/metabolism ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Neoplasms/immunology/therapy/microbiology ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; Male ; Female ; Adult ; Middle Aged ; }, abstract = {The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers. FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity. Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers.}, }
@article {pmid39057689, year = {2024}, author = {Vallianou, NG and Kounatidis, D and Psallida, S and Vythoulkas-Biotis, N and Adamou, A and Zachariadou, T and Kargioti, S and Karampela, I and Dalamaga, M}, title = {NAFLD/MASLD and the Gut-Liver Axis: From Pathogenesis to Treatment Options.}, journal = {Metabolites}, volume = {14}, number = {7}, pages = {}, pmid = {39057689}, issn = {2218-1989}, abstract = {Nonalcoholic fatty liver disease (NAFLD) poses an emerging threat topublic health. Nonalcoholic steatohepatitis (NASH) is reported to be the most rapidly rising cause of hepatocellular carcinoma in the western world. Recently, a new term has been proposed: metabolic dysfunction-associated steatotic liver disease (MASLD). The introduction of this new terminology has sparked a debate about the interchangeability of these terms. The pathogenesis of NAFLD/MASLD is thought to be multifactorial, involving both genetic and environmental factors. Among these factors, alterations in gut microbiota and gut dysbiosis have recently garnered significant attention. In this context, this review will further discuss the gut-liver axis, which refers to the bidirectional interaction between the human gut microbiota and the liver. Additionally, the therapeutic potential of probiotics, particularly next-generation probiotics and genetically engineered bacteria, will be explored. Moreover, the role of prebiotics, synbiotics, postbiotics, and phages as well as fecal microbiota transplantation will be analyzed. Particularly for lean patients with NAFLD/MASLD, who have limited treatment options, approaches that modify the diversity and composition of the gut microbiota may hold promise. However, due to ongoing safety concerns with approaches that modulate gut microbiota, further large-scale studies are necessary to better assess their efficacy and safety in treating NAFLD/MASLD.}, }
@article {pmid39056206, year = {2024}, author = {Jiang, X and Gao, X and Ding, J and Pang, B and Pei, Y and Zhao, Z and Zhao, N and Wang, Z and Chen, C and Gao, D and Yan, F and Wang, F and Liu, C and Zhang, Z and Li, Z and Zhao, Z}, title = {Fecal microbiota transplantation alleviates mild-moderate COVID-19 associated diarrhoea and depression symptoms: A prospective study of a randomized, double-blind clinical trial.}, journal = {Journal of medical virology}, volume = {96}, number = {8}, pages = {e29812}, doi = {10.1002/jmv.29812}, pmid = {39056206}, issn = {1096-9071}, support = {//Construction Funds of Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment from The First Hospital of Hebei Medical University; and other Hebei Province Projects/ ; //National Natural Science Foundation of China/ ; //The Natural Science Foundation of Hebei/ ; //Hebei Provincial Department of Human Resources and Social Security/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *COVID-19/therapy/complications ; *Diarrhea/therapy/microbiology/virology ; Male ; Female ; Double-Blind Method ; Middle Aged ; *Depression/therapy ; Prospective Studies ; Adult ; Aged ; Feces/microbiology/virology ; SARS-CoV-2 ; Treatment Outcome ; Aspartate Aminotransferases/blood ; Gastrointestinal Microbiome ; }, abstract = {Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.}, }
@article {pmid39055928, year = {2024}, author = {Lang, Y and Zhong, C and Guo, L and Liu, Z and Zuo, D and Chen, X and Ding, L and Huang, B and Li, B and Yuan, Y and Niu, Y and Qiu, J and Qian, C}, title = {Monoacylglycerol acyltransferase-2 inhibits colorectal carcinogenesis in APC[min+/-] mice.}, journal = {iScience}, volume = {27}, number = {7}, pages = {110205}, pmid = {39055928}, issn = {2589-0042}, abstract = {Monoacylglycerol acyltransferase-2 (MOGAT2), encodes MOGAT enzyme in the re-synthesis of triacylglycerol and protects from metabolism disorders. While, its precise involvement in colorectal cancer (CRC) progression remains inadequately understood. Our study demonstrated that knockout of Mogat2 in Apc[min/+] mice expedited intestinal tumor growth and progression, indicating that Mogat2 plays a tumor-suppressing role in CRC. Mechanically, Mogat2 deletion resulted in a significant alter the gut microbiota, while Fecal Microbiota Transplantation (FMT) experiments demonstrated that the gut microbiota in Mogat2 deleted mice promoted tumor growth. Furthermore, we identified Mogat2 as a functional regulator suppressing CRC cell proliferation and tumor growth by inhibiting the NF-κB signaling pathway in vivo. Collectively, these results provide novel insights into the protective double roles of Mogat2, inhibiting of NF-κB pathway and keeping gut microbiota homeostasis in colorectal cancer, which may help the development of novel cancer treatments for CRC.}, }
@article {pmid39055874, year = {2024}, author = {Chen, R and Wu, F and Zeng, G and Chen, Y and Lu, S and Huang, H}, title = {Therapeutic effect of fecal microbiota transplantation on rats with liver cirrhosis and its influence on gut microbiota.}, journal = {Iranian journal of basic medical sciences}, volume = {27}, number = {9}, pages = {1148-1154}, pmid = {39055874}, issn = {2008-3866}, abstract = {OBJECTIVES: This study aimed to explore the therapeutic effect of fecal microbiota transplantation (FMT) on liver cirrhosis-induced rat models by studying changes in intestinal flora distribution and liver pathology.<br><br>MATERIALS AND METHODS: Cirrhosis was induced in adult male Sprague-Dawley rats using carbon tetrachloride; successful establishment of the cirrhosis model was verified using hematoxylin and eosin (HE) staining. Rats were divided into normal control, cirrhosis model+normal saline, and cirrhosis model+FMT groups. Fecal intestinal flora was analyzed using 16S rRNA high-throughput sequencing for each group. Alpha diversity, beta diversity, and functional prediction analyses were performed. Additionally, rat liver tissue was subjected to HE staining to compare the degree of fibrosis and liver damage between the groups.<br><br>RESULTS: FMT significantly improved the diversity, richness, and uniformity of the intestinal flora in rats with liver cirrhosis. Notably, post-FMT, the abundance of lactobacillaceae, bacilli, and bacteroidia increased, while the abundance of clostridia decreased. Moreover, hepatic fibrosis improved after FMT.<br><br>CONCLUSION: The dysbiosis of intestinal flora in rats with liver cirrhosis improved after FMT. Thus, FMT can regulate intestinal flora, reduce liver inflammation, and improve hepatic fibrosis and cirrhosis.}, }
@article {pmid39054706, year = {2024}, author = {Lin, J and Chen, Y and Li, T and Zhu, C and Qiu, Y and Yu, E}, title = {Research Progress on Mechanisms of Modulating Gut Microbiota to Improve Symptoms of Major Depressive Disorder.}, journal = {Discovery medicine}, volume = {36}, number = {186}, pages = {1354-1362}, doi = {10.24976/Discov.Med.202436186.125}, pmid = {39054706}, issn = {1944-7930}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Depressive Disorder, Major/microbiology/therapy/immunology ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Brain-Gut Axis/physiology ; Animals ; }, abstract = {Major depressive disorder (MDD) is a clinical condition that significantly impacts patients' physical and mental well-being, quality of life, and social functioning. The pathogenesis of MDD remains unclear, but accumulating evidence suggests a close relationship between gut microbiota and the occurrence and progression of MDD. Gut microbiota refers to the microbial community in the human intestine, which engages in bidirectional communication with the host via the "gut-brain axis" and plays a pivotal role in influencing the host's metabolism, immune system, endocrine system, and nervous system. Modulating gut microbiota entails restoring the balance and function of the intestinal flora through methods such as probiotic intake, fecal transplantation, and dietary intervention. Such modulation has been shown to effectively alleviate depressive symptoms in the host. This review synthesizes recent advancements in research on gut microbiota modulation for ameliorating depressive symptoms and can serve as a foundation for further exploration of the gut microbiota's role in MDD and its potential therapeutic benefits.}, }
@article {pmid39054479, year = {2024}, author = {Boldrini, L and Chiloiro, G and Di Franco, S and Romano, A and Smiljanic, L and Tran, EH and Bono, F and Charles Davies, D and Lopetuso, L and De Bonis, M and Minucci, A and Giacò, L and Cusumano, D and Placidi, L and Giannarelli, D and Sala, E and Gambacorta, MA}, title = {MOREOVER: multiomics MR-guided radiotherapy optimization in locally advanced rectal cancer.}, journal = {Radiation oncology (London, England)}, volume = {19}, number = {1}, pages = {94}, pmid = {39054479}, issn = {1748-717X}, support = {Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; }, mesh = {*Rectal Neoplasms/radiotherapy/pathology/therapy ; Humans ; Neoadjuvant Therapy/methods ; Gastrointestinal Microbiome ; Magnetic Resonance Imaging ; Radiotherapy, Image-Guided/methods ; Chemoradiotherapy/methods ; Circulating Tumor DNA/genetics ; Biomarkers, Tumor ; Genomics/methods ; Male ; Female ; Multiomics ; }, abstract = {BACKGROUND: Complete response prediction in locally advanced rectal cancer (LARC) patients is generally focused on the radiomics analysis of staging MRI. Until now, omics information extracted from gut microbiota and circulating tumor DNA (ctDNA) have not been integrated in composite biomarkers-based models, thereby omitting valuable information from the decision-making process. In this study, we aim to integrate radiomics with gut microbiota and ctDNA-based genomics tracking during neoadjuvant chemoradiotherapy (nCRT).<br><br>METHODS: The main hypothesis of the MOREOVER study is that the incorporation of composite biomarkers with radiomics-based models used in the THUNDER-2 trial will improve the pathological complete response (pCR) predictive power of such models, paving the way for more accurate and comprehensive personalized treatment approaches. This is due to the inclusion of actionable omics variables that may disclose previously unknown correlations with radiomics. Aims of this study are: - to generate longitudinal microbiome data linked to disease resistance to nCRT and postulate future therapeutic strategies in terms of both type of treatment and timing, such as fecal microbiota transplant in non-responding patients. - to describe the genomics pattern and ctDNA data evolution throughout the nCRT treatment in order to support the prediction outcome and identify new risk-category stratification agents. - to mine and combine collected data through integrated multi-omics approaches (radiomics, metagenomics, metabolomics, metatranscriptomics, human genomics, ctDNA) in order to increase the performance of the radiomics-based response predictive model for LARC patients undergoing nCRT on MR-Linac.<br><br>EXPERIMENTAL DESIGN: The objective of the MOREOVER project is to enrich the phase II THUNDER-2 trial (NCT04815694) with gut microbiota and ctDNA omics information, by exploring the possibility to enhance predictive performance of the developed model. Longitudinal ctDNA genomics, microbiome and genomics data will be analyzed on 7 timepoints: prior to nCRT, during nCRT on a weekly basis and prior to surgery. Specific modelling will be performed for data harvested, according to the TRIPOD statements.<br><br>DISCUSSION: We expect to find differences in fecal microbiome, ctDNA and radiomics profiles between the two groups of patients (pCR and not pCR). In addition, we expect to find a variability in the stability of the considered omics features over time. The identified profiles will be inserted into dedicated modelling solutions to set up a multiomics decision support system able to achieve personalized treatments.}, }
@article {pmid39053865, year = {2024}, author = {Lin, L and Tang, R and Liu, Y and Li, Z and Li, H and Yang, H}, title = {The brain-protective mechanism of fecal microbiota transplantation from young donor mice in the natural aging process via exosome, gut microbiota, and metabolomics analyses.}, journal = {Pharmacological research}, volume = {207}, number = {}, pages = {107323}, doi = {10.1016/j.phrs.2024.107323}, pmid = {39053865}, issn = {1096-1186}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Brain/metabolism ; *Aging ; *Metabolomics ; *MicroRNAs/metabolism ; *Exosomes/metabolism ; Male ; *Mice, Inbred C57BL ; Mice ; Oxidative Stress ; Cytokines/metabolism/blood ; }, abstract = {The natural aging process is accompanied by changes in exosomes, gut microbiota, and metabolites. This study aimed to reveal the anti-aging effect and mechanisms of fecal microbiota transplantation (FMT) from young donors on the natural aging process in mice by analyzing exosomes, gut microbiota, and metabolomics. Aging-relevant telomeric length, oxidative stress indexes in brain tissue, and serum cytokine levels were measured. Flow analysis of T-regulatory (Treg), CD4[+], and CD8[+] cells was performed, and the expression levels of aging-related proteins were quantified. High-throughput sequencing technology was used to identify differentially expressed serum exosomal miRNAs. Fecal microbiota was tested by 16 S rDNA sequencing. Changes in fecal metabolites were analyzed by UPLC-Q-TOF/MS. The results indicated that the expression of mmu-miR-7010-5p, mmu-miR-376b-5p, mmu-miR-135a-5p, and mmu-miR-3100-5p by serum exosomes was down-regulated and the abundance of opportunistic bacteria (Turicibacter, Allobaculum, Morganella.) was decreased, whereas the levels of protective bacteria (Akkermansia, Muribaculaceae, Helicobacter.) were increased after FMT. Metabolic analysis identified 25 potential biomarkers. Correlation analysis between the gut microbiota and metabolites suggested that the relative abundance of protective bacteria was positively correlated with the levels of spermidine and S-adenosylmethionine. The study indicated that FMT corrected brain injury due to aging via lipid metabolism, the metabolism of cofactors and vitamins, and amino acid metabolism.}, }
@article {pmid39052747, year = {2024}, author = {Kelly, BJ and Kwon, JH and Woodworth, MH}, title = {Escape Velocity-the Launch of Microbiome Therapies.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {1}, pages = {2-4}, pmid = {39052747}, issn = {1537-6613}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; U54 CK000601/CK/NCEZID CDC HHS/United States ; K23AI144036//National Institute of Allergy and Infectious Diseases/ ; U54CK000601/CC/CDC HHS/United States ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/therapy/microbiology ; *Clostridioides difficile ; *Gastrointestinal Microbiome ; United States ; Microbiota ; United States Food and Drug Administration ; }, abstract = {Food and Drug Administration approval of the first microbiome therapies represents a true expansion the treatment paradigm for Clostridioides difficile but raises new questions about the future role of fecal microbiota transplantation. The authors outline the advances in microbiome therapeutic development that have addressed fecal microbiota transplantation's (FMT's) inherent limitations of safety and scalability. The authors also suggest that as microbiome therapeutic development continues for other indications, FMT will likely remain a necessary model of human microbiota dynamics for translational research.}, }
@article {pmid39047173, year = {2024}, author = {Weber, D and Meedt, E and Poeck, H and Thiele-Orberg, E and Hiergeist, A and Gessner, A and Holler, E}, title = {Fecal Microbiota Transfer in Acute Graft-versus-Host Disease following Allogeneic Stem Cell Transplantation.}, journal = {Visceral medicine}, volume = {40}, number = {4}, pages = {1-6}, pmid = {39047173}, issn = {2297-4725}, abstract = {BACKGROUND: Acute graft-versus-host disease (GvHD) is a major and sometimes lethal complication following allogeneic stem cell transplantation (aSCT). In the last 10 years, a massive loss of microbiota diversity with suppression of commensal bacteria and their protective metabolites has been identified as a major risk factor of GvHD.<br><br>SUMMARY: Since 2018, several studies have been published showing some efficacy of fecal microbiota transfer (FMT) in aSCT patients. FMT was used (1) to eliminate antibiotic resistant bacteria, (2) to restore microbiota diversity after hematopoietic recovery, or (3) in most cases to treat steroid-resistant GvHD. Overall response rates between 30 and 50% have been reported, but randomized trials are still pending. Newer approaches try to evaluate the role of prophylactic FMT in order to prevent GvHD and other complications. Although aSCT patients are heavily immunosuppressed, no major safety concerns regarding FMT have been reported so far.<br><br>KEY MESSAGE: FMT is a promising approach for modulation of GvHD after aSCT and should be further explored in randomized trials.}, }
@article {pmid39045766, year = {2024}, author = {Stair, SL and Yoon, JH and Dymanus, KA and Lee, UJ and Adelstein, SA}, title = {Fecal incontinence is not associated with UTI: A contemporary case-control study.}, journal = {Neurourology and urodynamics}, volume = {43}, number = {8}, pages = {1910-1915}, doi = {10.1002/nau.25544}, pmid = {39045766}, issn = {1520-6777}, mesh = {Humans ; Female ; Male ; *Fecal Incontinence/epidemiology ; *Urinary Tract Infections/epidemiology/diagnosis ; Middle Aged ; Case-Control Studies ; Aged ; Retrospective Studies ; Risk Factors ; Prevalence ; }, abstract = {INTRODUCTION: Urinary tract infections (UTIs) are a leading cause of infection in adults. The most common cause is gastrointestinal bacteria ascending the urethra into the bladder. Studies showing fecal incontinence (FI) is a risk factor for UTI have been limited to nursing home populations. Healthy patients with recurrent UTI, especially women, often receive counseling, suggesting improper personal hygiene contributes to UTIs. This advice can be stigmatizing. Given UTI prevalence, it is important to elucidate risk factors for improved diagnosis, treatment, and patient education. Our objective was to perform a hospital-centered, retrospective case-control analysis to assess the effect of FI on UTI development in ambulatory patients.<br><br>METHODS: Patients (n&#x2009;=&#x2009;3035) with a diagnosis of FI were identified from a single institution and propensity score-matched with screening colonoscopy patients (n&#x2009;=&#x2009;3035) from 2018 to 2021. Patients were matched on age, sex, race, ethnicity, body mass index, and comorbidities, for example, diabetes, vesicoureteral reflux, and urinary incontinence. The association between FI and UTI was tested using Pearson's &#x3c7;[2] test.<br><br>RESULTS: Median age was 64 years with more females than males (73.81% vs. 71.20% female for case/control, p&#x2009;=&#x2009;0.02). Patients with FI were more often to have concurrent urinary incontinence (18.62% vs. 10.25% for case/control, p&#x2009;<&#x2009;0.001), as well as specifically urgency incontinence (13.28% vs. 11.57% for case/control, p&#x2009;=&#x2009;0.04). There was no significant difference in the incidence of UTI between patients with FI and those presenting for screening colonoscopy (p&#x2009;=&#x2009;0.44).<br><br>CONCLUSION: FI was not associated with an increased number of UTIs. Based on our results, current stigmatizing beliefs regarding the association between FI and UTI should be reevaluated.}, }
@article {pmid39044834, year = {2024}, author = {Tabrizi, E and Pourteymour Fard Tabrizi, F and Mahmoud Khaled, G and Sestito, MP and Jamie, S and Boone, BA}, title = {Unraveling the gut microbiome's contribution to pancreatic ductal adenocarcinoma: mechanistic insights and therapeutic perspectives.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1434771}, pmid = {39044834}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Carcinoma, Pancreatic Ductal/therapy/microbiology/immunology ; *Pancreatic Neoplasms/microbiology/therapy/immunology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {The gut microbiome plays a significant role in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), influencing oncogenesis, immune responses, and treatment outcomes. Studies have identified microbial species like Porphyromonas gingivalis and Fusobacterium nucleatum, that promote PDAC progression through various mechanisms. Additionally, the gut microbiome affects immune cell activation and response to immunotherapy, including immune checkpoint inhibitors and CAR-T therapy. Specific microbes and their metabolites play a significant role in the effectiveness of immune checkpoint inhibitors (ICIs). Alterations in the gut microbiome can either enhance or diminish responses to PD-1/PD-L1 and CTLA-4 blockade therapy. Additionally, bacterial metabolites like trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS) impact antitumor immunity, offering potential targets to augment immunotherapy responses. Modulating the microbiome through fecal microbiota transplantation, probiotics, prebiotics, dietary changes, and antibiotics shows promise in PDAC treatment, although outcomes are highly variable. Dietary modifications, particularly high-fiber diets and specific fat consumption, influence microbiome composition and impact cancer risk. Combining microbiome-based therapies with existing treatments holds potential for improving PDAC therapy outcomes, but further research is needed to optimize their effectiveness.}, }
@article {pmid39043769, year = {2024}, author = {Song, Y and Cui, Y and Wang, Y and Wang, T and Zhong, Y and Liu, J and Zheng, X}, title = {The effect and potential mechanism of inulin combined with fecal microbiota transplantation on early intestinal immune function in chicks.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {16973}, pmid = {39043769}, issn = {2045-2322}, support = {21ZGN16//the key technology research project of the Changchun Key R&amp;D Program/ ; 2021YFD2101003-2//the National Key R&amp;D Program of China/ ; 20220203096SF//the Science and Technology Development Plan Program of Jilin Province/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Inulin/pharmacology ; *Chickens/microbiology/immunology ; Gastrointestinal Microbiome/drug effects ; Intestines/immunology/microbiology ; Intestinal Mucosa/metabolism/immunology/microbiology ; Cecum/microbiology ; }, abstract = {Our previous research found that fecal microbiota transplantation (FMT) and inulin synergistically affected the intestinal barrier and immune system function in chicks. However, does it promote the early immunity of the poultry gut-associated lymphoid tissue (GALT)? How does it regulate the immunity? We evaluated immune-related indicators in the serum, cecal tonsil, and intestine to determine whether FMT synergistic inulin had a stronger impact on gut health and which gene expression regulation was affected. The results showed that FMT synergistic inulin increased TGF-β secretion and intestinal goblet cell number and MUC2 expression on day 14. Expression of BAFFR, PAX5, CXCL12, and IL-2 on day 7 and expression of CXCR4 and IL-2 on day 14 in the cecal tonsils significantly increased. The transcriptome indicated that CD28 and CTLA4 were important regulatory factors in intestinal immunity. Correlation analysis showed that differential genes were related to the immunity and development of the gut and cecal tonsil. FMT synergistic inulin promoted the development of GALT, which improved the early-stage immunity of the intestine by regulating CD28 and CTLA4. This provided new measures for replacing antibiotic use and reducing the use of therapeutic drugs while laying a technical foundation for achieving anti-antibiotic production of poultry products.}, }
@article {pmid39043421, year = {2024}, author = {Fan, C and Li, R and Wang, L and Li, K and Jia, X and Gao, H and Zhang, B and Xu, X and Qian, S}, title = {Fecal Microbiota Transplantation for Severe Infant Botulism, China.}, journal = {Emerging infectious diseases}, volume = {30}, number = {8}, pages = {1732-1734}, pmid = {39043421}, issn = {1080-6059}, mesh = {*Botulism/therapy/microbiology ; Humans ; Infant ; Male ; *Fecal Microbiota Transplantation ; China ; Feces/microbiology ; Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {Infant botulism in a 4-month-old boy in China who continued to excrete toxins for over a month despite antitoxin therapy was further treated with fecal microbiota transplantation. After treatment, we noted increased gut microbial diversity and altered fecal metabolites, which may help reduce intestinal pH and enhance anti-inflammatory capabilities.}, }
@article {pmid39042929, year = {2024}, author = {Leclercq, S}, title = {Involvement of the gut microbiome-brain axis in alcohol use disorder.}, journal = {Alcohol and alcoholism (Oxford, Oxfordshire)}, volume = {59}, number = {5}, pages = {}, doi = {10.1093/alcalc/agae050}, pmid = {39042929}, issn = {1464-3502}, support = {//Fonds de la Recherche Scientifique - FNRS/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Brain-Gut Axis/physiology ; *Alcoholism/microbiology/therapy ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Prebiotics ; Animals ; Brain/metabolism ; }, abstract = {The human intestine is colonized by a variety of microorganisms that influence the immune system, the metabolic response, and the nervous system, with consequences for brain function and behavior. Unbalance in this microbial ecosystem has been shown to be associated with psychiatric disorders, and altered gut microbiome composition related to bacteria, viruses, and fungi has been well established in patients with alcohol use disorder. This review describes the gut microbiome-brain communication pathways, including the ones related to the vagus nerve, the inflammatory cytokines, and the gut-derived metabolites. Finally, the potential benefits of microbiota-based therapies for the management of alcohol use disorder, such as probiotics, prebiotics, and fecal microbiota transplantation, are also discussed.}, }
@article {pmid39042868, year = {2024}, author = {Moutsoglou, D and Vaughn, BP}, title = {Rethinking Faecal Microbiota Transplant for Pouchitis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {18}, number = {11}, pages = {1739-1740}, doi = {10.1093/ecco-jcc/jjae100}, pmid = {39042868}, issn = {1876-4479}, support = {T32 HL144472/HL/NHLBI NIH HHS/United States ; }, }
@article {pmid39041052, year = {2024}, author = {Ezenabor, EH and Adeyemi, AA and Adeyemi, OS}, title = {Gut Microbiota and Metabolic Syndrome: Relationships and Opportunities for New Therapeutic Strategies.}, journal = {Scientifica}, volume = {2024}, number = {}, pages = {4222083}, pmid = {39041052}, issn = {2090-908X}, abstract = {Since its discovery, numerous studies have shown the role of the microbiota in well-being and disease. The gut microbiota represents an essential factor that plays a multidirectional role that affects not just the gut but also other parts of the body, including the brain, endocrine system, humoral system, immune system, and metabolic pathways, as well as host-microbiome interactions. Through a comprehensive analysis of existing literature using the desktop research methodology, this review elucidates the mechanisms by which gut microbiota dysbiosis contributes to metabolic dysfunction, including obesity, dyslipidaemia, hypertension, atherosclerosis, hyperuricemia, and hyperglycaemia. Furthermore, it examines the bidirectional communication pathways between gut microbiota and host metabolism, highlighting the role of microbial-derived metabolites, immune modulation, and gut barrier integrity in shaping metabolic homeostasis. Importantly, the review identifies promising therapeutic strategies targeting the gut microbiota as potential interventions for metabolic syndrome, including probiotics, prebiotics, symbiotics, dietary modifications, and faecal microbiota transplantation. By delineating the bidirectional interactions between gut microbiota and metabolic syndrome, the review not only advances our understanding of disease pathophysiology but also underscores the potential for innovative microbiota-based interventions to mitigate the global burden of metabolic syndrome and its associated complications.}, }
@article {pmid39040423, year = {2024}, author = {Zhang, X and Li, Y and Li, B and Wu, J and Zhang, J and Ding, X}, title = {Washed microbiota transplantation in an elderly patient with lymphocytic leukemia and Clostridioides difficile infection: A case report illustrating a triumph over complexity.}, journal = {Heliyon}, volume = {10}, number = {13}, pages = {e32450}, pmid = {39040423}, issn = {2405-8440}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is recommended for treating patients with recurrent Clostridioides difficile infection (CDI). However, the therapeutic efficacy of FMT in elderly patients with complex medical conditions remains uncertain. The new method of FMT, washed microbiota transplantation (WMT) has been widely used in China to improve the safety of transplantation.<br><br>CASE REPORT: A 94-year-old man with chronic lymphocytic leukemia (CLL) was admitted to our hospital due to recurrent diarrhea persisting for eight months. The patient had experienced multiple relapses of CDI despite receiving standard therapies. He underwent colonic transendoscopic enteral tubing (TET) and subsequently received WMT during the procedure. Following the treatment, no episodes of diarrhea or adverse events were observed, and the patient remained stable over a three-month follow-up period.<br><br>CONCLUSION: This case demonstrates the efficacy and safety of WMT in treating elderly patients with CLL. The successful management of this case offers valuable clinical insights into the use of WMT for elderly CDI patients with complex medical conditions. Moreover, this report contributes practical experience regarding the administration of WMT through the colonic TET.}, }
@article {pmid39040013, year = {2024}, author = {Sasidharan Pillai, S and Gagnon, CA and Foster, C and Ashraf, AP}, title = {Exploring the Gut Microbiota: Key Insights Into Its Role in Obesity, Metabolic Syndrome, and Type 2 Diabetes.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {109}, number = {11}, pages = {2709-2719}, pmid = {39040013}, issn = {1945-7197}, support = {K12 TR004769/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/microbiology/therapy/metabolism ; *Obesity/microbiology/metabolism/therapy ; *Metabolic Syndrome/microbiology/therapy/metabolism ; *Dysbiosis/therapy/microbiology ; Fecal Microbiota Transplantation ; Animals ; Energy Metabolism/physiology ; }, abstract = {The gut microbiota (GM), comprising trillions of microorganisms in the gastrointestinal tract, is a key player in the development of obesity and related metabolic disorders, such as type 2 diabetes (T2D), metabolic syndrome (MS), and cardiovascular diseases. This mini-review delves into the intricate roles and mechanisms of the GM in these conditions, offering insights into potential therapeutic strategies targeting the microbiota. The review elucidates the diversity and development of the human GM, highlighting its pivotal functions in host physiology, including nutrient absorption, immune regulation, and energy metabolism. Studies show that GM dysbiosis is linked to increased energy extraction, altered metabolic pathways, and inflammation, contributing to obesity, MS, and T2D. The interplay between dietary habits and GM composition is explored, underscoring the influence of diet on microbial diversity and metabolic functions. Additionally, the review addresses the impact of common medications and therapeutic interventions like fecal microbiota transplantation on GM composition. The evidence so far advocates for further research to delineate the therapeutic potential of GM modulation in mitigating obesity and metabolic diseases, emphasizing the necessity of clinical trials to establish effective and sustainable treatment protocols.}, }
@article {pmid39036641, year = {2024}, author = {He, J and Wu, J and Liu, J and Wu, H and Hua, H}, title = {Cognitive impairment and the gut-brain axis during 2014-2023: a bibliometric analysis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1407956}, pmid = {39036641}, issn = {1664-2295}, abstract = {BACKGROUND: The burden on society grows as the number of individuals with cognitive impairment rises. Numerous research have discovered a connection between cognitive impairment and the gut-brain axis, which is useful in examining the pathophysiology of cognitive impairment and potential therapeutic approaches. As a result, this article explores developments and trends in the research concerning the gut-brain axis and cognitive impairment through a bibliometric analysis of the contributions made by various countries/regions, institutions, authors, and journals.<br><br>METHODS: We looked for articles on gut-brain axis and cognitive impairment from 2014 to 2023 in the Web of Science Core Collection. For the descriptive analysis, figures and tables were taken using GraphPad Prism 6 and WPS Office 2024. For the visual analysis of the countries/regions, institutions, authors, and keywords, VOSviewer was utilized.<br><br>RESULTS: We obtained 458 publications from 1 January 2014 to 9 September 2023. The country with the most publications (175, 38.21%) was China. The country with the greatest total number of citations (3,138, 17.22%) was the United States of America. The highest number of articles (15, 3.26%) was issued by Zhejiang University. The most published first author is Karsas M. In this field, Nutrients have published the most articles (24). The most often occurring keywords include "Alzheimer's disease," "cognitive impairment," "gut microbiota," "inflammation," "diet," etc. "Stroke," "tau," "probiotics," "exercise," "fecal microbiota transplantation," etc. emerged later.<br><br>CONCLUSION: An increasing amount of research has focused on the connection between cognitive impairment and the gut-brain axis. In this area, the United States of America and China have both made significant contributions. The author team's collaboration has to be improved. Our study contributes to understanding the field's current state and predicting its future trend.}, }
@article {pmid39036426, year = {2024}, author = {Sun, W and Reeves, W and Fagan, MM and Welch, CB and Scheulin, KM and Sneed, SE and Callaway, TR and Duberstein, KJ and West, FD and Zhao, Q}, title = {Evaluation of Brain Function Recovery After Traumatic Brain Injury Treatment in a Porcine Model by Cross-Group Temporal-Spatial Correlation Analysis.}, journal = {Neurotrauma reports}, volume = {5}, number = {1}, pages = {617-627}, pmid = {39036426}, issn = {2689-288X}, abstract = {Traumatic brain injury (TBI), a significant global health issue, is affecting ∼69 million annually. To better understand TBI's impact on brain function and assess the efficacy of treatments, this study uses a novel temporal-spatial cross-group approach with a porcine model, integrating resting-state functional magnetic resonance imaging (rs-fMRI) for temporal and arterial spin labeling for spatial information. Our research used 18 four-week-old pigs divided into three groups: TBI treated with saline (SLN, n = 6), TBI treated with fecal microbial transplant (FMT, n = 6), and a sham group (sham, n = 6) with only craniectomy surgery as the baseline. By applying machine learning techniques-specifically, independent component analysis and sparse dictionary learning-across seven identified resting-state networks, we assessed the temporal and spatial correlations indicative of treatment efficacy. Both temporal and spatial analyses revealed a consistent increase of correlation between the FMT and sham groups in the executive control and salience networks. Our results are further evidenced by a simulation study designed to mimic the progression of TBI severity through the introduction of variable Gaussian noise to an independent rs-fMRI dataset. The results demonstrate a decreasing temporal correlation between the sham and TBI groups with increasing injury severity, consistent with the experimental results. This study underscores the effectiveness of the methodology in evaluating post-TBI treatments such as the FMT. By presenting comprehensive experimental and simulated data, our research contributes significantly to the field and opens new paths for future investigations into TBI treatment evaluations.}, }
@article {pmid39036341, year = {2024}, author = {You, M and Chen, N and Yang, Y and Cheng, L and He, H and Cai, Y and Liu, Y and Liu, H and Hong, G}, title = {The gut microbiota-brain axis in neurological disorders.}, journal = {MedComm}, volume = {5}, number = {8}, pages = {e656}, pmid = {39036341}, issn = {2688-2663}, abstract = {Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as the microbiota-gut-brain axis (MGBA). The MGBA influences the host's nervous system development, emotional regulation, and cognitive function through neurotransmitters, immune modulation, and metabolic pathways. Factors like diet, lifestyle, genetics, and environment shape the gut microbiota composition together. Most research have explored how gut microbiota regulates host physiology and its potential in preventing and treating neurological disorders. However, the individual heterogeneity of gut microbiota, strains playing a dominant role in neurological diseases, and the interactions of these microbial metabolites with the central/peripheral nervous systems still need exploration. This review summarizes the potential role of gut microbiota in driving neurodevelopmental disorders (autism spectrum disorder and attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's and Parkinson's disease), and mood disorders (anxiety and depression) in recent years and discusses the current clinical and preclinical gut microbe-based interventions, including dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation. It also puts forward the current insufficient research on gut microbiota in neurological disorders and provides a framework for further research on neurological disorders.}, }
@article {pmid39035457, year = {2024}, author = {Lin, Z and Jiang, T and Chen, M and Ji, X and Wang, Y}, title = {Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects.}, journal = {Open life sciences}, volume = {19}, number = {1}, pages = {20220910}, pmid = {39035457}, issn = {2391-5412}, abstract = {Sleep is crucial for wellness, and emerging research reveals a profound connection to gut microbiota. This review explores the bidirectional relationship between gut microbiota and sleep, exploring the mechanisms involved and the therapeutic opportunities it presents. The gut-brain axis serves as a conduit for the crosstalk between gut microbiota and the central nervous system, with dysbiosis in the microbiota impairing sleep quality and vice versa. Diet, circadian rhythms, and immune modulation all play a part. Specific gut bacteria, like Lactobacillus and Bifidobacterium, enhance sleep through serotonin and gamma-aminobutyric acid production, exemplifying direct microbiome influence. Conversely, sleep deprivation reduces beneficial bacteria, exacerbating dysbiosis. Probiotics, prebiotics, postbiotics, and fecal transplants show therapeutic potential, backed by animal and human research, yet require further study on safety and long-term effects. Unraveling this intricate link paves the way for tailored sleep therapies, utilizing microbiome manipulation to improve sleep and health. Accelerated research is essential to fully tap into this promising field for sleep disorder management.}, }
@article {pmid39034613, year = {2024}, author = {Krigul, KL and Feeney, RH and Wongkuna, S and Aasmets, O and Holmberg, SM and Andreson, R and Puértolas-Balint, F and Pantiukh, K and Sootak, L and Org, T and Tenson, T and Org, E and Schroeder, BO}, title = {A history of repeated antibiotic usage leads to microbiota-dependent mucus defects.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2377570}, pmid = {39034613}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Animals ; *Anti-Bacterial Agents/pharmacology ; Mice ; *Fecal Microbiota Transplantation ; *Mucus/metabolism/microbiology ; *Bacteria/classification/genetics/drug effects/isolation &amp; purification/metabolism ; Intestinal Mucosa/microbiology/metabolism/drug effects ; Male ; Female ; Feces/microbiology ; Adult ; Middle Aged ; Akkermansia ; Mice, Inbred C57BL ; Colon/microbiology ; Bacteroides fragilis/drug effects ; }, abstract = {Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and ultimately changes the gut microbiota community. However, the physiological effects of repeated - but not recent - antibiotic usage on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from the deeply phenotyped Estonian Microbiome Cohort (EstMB), we here utilized human-to-mouse fecal microbiota transplantation to explore long-term impacts of repeated antibiotic use on intestinal mucus function. While a healthy mucus layer protects the intestinal epithelium against infection and inflammation, using ex vivo mucus function analyses of viable colonic tissue explants, we show that microbiota from humans with a history of repeated antibiotic use causes reduced mucus growth rate and increased mucus penetrability compared to healthy controls in the transplanted mice. Moreover, shotgun metagenomic sequencing identified a significantly altered microbiota composition in the antibiotic-shaped microbial community, with known mucus-utilizing bacteria, including Akkermansia muciniphila and Bacteroides fragilis, dominating in the gut. The altered microbiota composition was further characterized by a distinct metabolite profile, which may be caused by differential mucus degradation capacity. Consequently, our proof-of-concept study suggests that long-term antibiotic use in humans can result in an altered microbial community that has reduced capacity to maintain proper mucus function in the gut.}, }
@article {pmid39034349, year = {2024}, author = {Zhuang, Y and Liu, S and Gao, D and Xu, Y and Jiang, W and Chen, T and Xiao, J and Wang, J and Hou, G and Li, S and Zhao, X and Huang, Y and Li, S and Zhang, S and Li, M and Wang, W and Li, S and Cao, Z}, title = {The Bifidobacterium-dominated fecal microbiome in dairy calves shapes the characteristic growth phenotype of host.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {59}, pmid = {39034349}, issn = {2055-5008}, mesh = {Animals ; *Feces/microbiology ; Cattle ; *RNA, Ribosomal, 16S/genetics ; *Bifidobacterium/genetics/growth &amp; development ; *Gastrointestinal Microbiome ; Mice ; *Fecal Microbiota Transplantation/methods ; Phenotype ; Probiotics/administration &amp; dosage ; Phylogeny ; DNA, Bacterial/genetics ; }, abstract = {The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.}, }
@article {pmid39032279, year = {2024}, author = {Zhang, H and Hao, Z and Zhang, R and Tong, J and Wang, X and Liu, J and Gao, Y and Wang, X and Su, Q and Wen, H and Fan, Y and Liu, F and Li, X and Tong, C and Wang, X}, title = {Artemisia argyi polyphenols Attenuates DSS-induced colitis in mice by regulating the structural composition of gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {132}, number = {}, pages = {155897}, doi = {10.1016/j.phymed.2024.155897}, pmid = {39032279}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dextran Sulfate ; *Polyphenols/pharmacology ; *Artemisia/chemistry ; Mice ; *Colitis, Ulcerative/chemically induced/drug therapy ; Male ; Mice, Inbred C57BL ; Colon/drug effects/microbiology ; Anti-Inflammatory Agents/pharmacology ; Disease Models, Animal ; Colitis/chemically induced/drug therapy ; Oxidative Stress/drug effects ; Plant Extracts/pharmacology/chemistry ; }, abstract = {BACKGROUND: Intestinal health is affected by heredity, lifestyle, and structure of gut microbiota. The imbalance of symbiotic and harmful bacteria in gut microbiota may increase the occurrence of colonic inflammation. Supplementary A. muciniphila can improve the survival rate of colitis mice, reduce colon tissue injury, and the expression of anti-inflammatory factors was upregulated. Artemisia argyi has been reported to have anti-inflammatory, antioxidant, bactericidal, and immunomodulatory effects. However, its anti-inflammatory effect and mechanism, and its influence on gut microbiota and metabolites are still unclear yet.<br><br>PURPOSE: To explore whether Artemisia argyi Polyphenols(AAPs) can alleviate ulcerative colitis (UC) by changing gut microbiota.<br><br>METHODS: The therapeutic effect of AAPs on colitis was investigated by inducing ulcerative colitis in mice using dextran sodium sulfate (DSS) and administering different doses of AAPs orally to mice. Exploring the levels of inflammatory proteins, oxidative stress proteins, and barrier proteins using western blotting and immunofluorescence, and explored the structural changes of gut microbiota and its metabolites. Meanwhile, in order to explore whether the role of AAPs in alleviating colitis is based on the regulation of gut microbiota structure, we conducted fecal microbiota transplantation (FMT).<br><br>RESULTS: It showed that AAPs and FMT trial alleviated DSS-induced colonic injury, including clinical parameters and pathological injury of colon tissue, reduction in the expression of inflammatory proteins: IL-6, TNF-&#x3b1;, p-p65, p-I&#x3ba;B&#x3b1;, and increase in the expression of antioxidant proteins: Nrf2, NQO-1 and HO-1 and barrier proteins: Claudin-1, Occludin, ZO-1 and MUC2. AAPs and FMT promoted the content of beneficial bacteria, such as Butyricimonas and Lactobacillus, and the content of beneficial metabolites for instance acetic acid, butyric acid, and valeric acid has also increased.<br><br>CONCLUSION: These results suggested that AAPs might improve DSS-induced colonic injury by changing the structural of gut microbiota while promoting the synthesis of fatty acids in the intestine, thereby providing a theoretical basis for using AAPs to treat ulcerative colitis.}, }
@article {pmid39031494, year = {2025}, author = {Koller, T and Vrbova, P and Kubanek, N and Zilincanova, D and Selcanova, SA and Havaj, DJ and Skladany, L}, title = {Assessment of intestinal inflammation via fecal calprotectin for early prediction of adverse outcomes in advanced chronic liver disease.}, journal = {United European gastroenterology journal}, volume = {13}, number = {3}, pages = {305-316}, pmid = {39031494}, issn = {2050-6414}, mesh = {Humans ; Male ; Female ; *Leukocyte L1 Antigen Complex/analysis ; Middle Aged ; *Feces/chemistry ; Prognosis ; Aged ; Biomarkers/analysis ; Predictive Value of Tests ; Risk Assessment/methods ; Adult ; Registries ; Case-Control Studies ; Proportional Hazards Models ; Chronic Disease ; *Liver Diseases ; Liver Transplantation/statistics &amp; numerical data ; *Liver Cirrhosis/mortality/complications ; Severity of Illness Index ; }, abstract = {BACKGROUND AND AIMS: Intestinal inflammation assessed by fecal calprotectin (F-CAL) in advanced chronic liver disease (ACLD) may represent an early sign of intestinal barrier dysfunction. We aimed to explore the usefulness of F-CAL testing in ACLD in the prediction of adverse outcomes (AO, death, or LT) and refinement of prognostic stratification.<br><br>PATIENTS AND METHODS: We explored the RH7 cirrhosis registry comprising consecutive hospitalized patients and a control group with data on disease phenotype, demographics, anthropometrics, prognostic indices, and medication. The F-CAL was evaluated on admission and reported in multiples of the upper limit of normal or terciles. Predictive power was tested in the Cox model for AO over 180&#xa0;days. Additional risk refinement by F-CAL was tested for both groups.<br><br>RESULTS: We enrolled 263 cases in the study group with a median age of 57.2&#xa0;years, M/F ratio 167/96, with alcohol, metabolic dysfunction-associated steatotic liver disease, MetALD, and viral etiologies in 72.2%, 9.1, 8.0, 3.4%. The median F-CAL was 3.92&#xa0;&#xd7;&#xa0;ULN. The control group comprised 108 cases. The adjusted Cox model confirmed F-CAL (hazard ratio [HR]&#xa0;=&#xa0;1.05, p&#xa0;<&#xa0;0.001) and F-CAL terciles (HR&#xa0;=&#xa0;1.413, p&#xa0;=&#xa0;0.009) as independent predictors of AO. F-CAL terciles had higher predictive accuracy in CLIF-C-AD<50 (HR&#xa0;=&#xa0;2.49, p&#xa0;=&#xa0;0.013) and Child stages A and B (HR&#xa0;=&#xa0;1.706, p&#xa0;=&#xa0;0.025), in whom high F-CAL (cut-off >11&#xa0;&#xd7;&#xa0;ULN) could identify patients having 2-3 times higher risk of AO. This approach has been validated in the control group.<br><br>CONCLUSION: Among hospitalized patients with ACLD, F-CAL values were independently proportional to the risk of AO, particularly in early disease stages when high F-CAL values could refine prognostic stratification.}, }
@article {pmid39030978, year = {2024}, author = {Dong, Y and Dong, J and Xiao, H and Li, Y and Wang, B and Zhang, S and Cui, M}, title = {A gut microbial metabolite cocktail fights against obesity through modulating the gut microbiota and hepatic leptin signaling.}, journal = {Journal of the science of food and agriculture}, volume = {104}, number = {15}, pages = {9356-9367}, doi = {10.1002/jsfa.13758}, pmid = {39030978}, issn = {1097-0010}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Obesity/metabolism/microbiology/drug therapy ; Mice ; Male ; *Mice, Inbred C57BL ; *Leptin/metabolism ; Female ; *Liver/metabolism ; *Diet, High-Fat/adverse effects ; *Signal Transduction/drug effects ; *Bacteria/classification/genetics/metabolism/isolation &amp; purification ; Butyric Acid/metabolism ; Fecal Microbiota Transplantation ; Humans ; Indoles/metabolism/pharmacology ; Propionates/metabolism ; Pentanoic Acids ; }, abstract = {BACKGROUND: Excessive body weight and obesity elevate the risk of chronic non-communicable diseases. The judicious application of the gut microbiome, encompassing both microorganisms and their derived compounds, holds considerable promise in the treatment of obesity.<br><br>RESULTS: In this study, we showed that a cocktail of gut microbiota-derived metabolites, comprising indole 3-propionic acid (IPA), sodium butyrate (SB) and valeric acid (VA), alleviated various symptoms of obesity in both male and female mice subjected to a high-fat diet (HFD). The 16S ribosomal RNA (rRNA) sequencing revealed that administering the cocktail via oral gavage retained the gut microbiota composition in obese mice. Fecal microbiota transplantation using cocktail-treated mice as donors mitigated the obesity phenotype of HFD-fed mice. Transcriptomic sequencing analysis showed that the cocktail preserved the gene expression profile of hepatic tissues in obese mice, especially up-regulated the expression level of leptin receptor. Gene delivery via in vivo fluid dynamics further validated that the anti-obesity efficacy of the cocktail was dependent on leptin signaling at least partly. The cocktail also inhibited the expression of appetite stimulators in hypothalamus. Together, the metabolite cocktail combated adiposity by retaining the gut microbiota configuration and activating the hepatic leptin signaling pathway.<br><br>CONCLUSIONS: Our findings provide a sophisticated regulatory network between the gut microbiome and host, and highlight a cocktail of gut microbiota-derived metabolites, including IPA, SB, and VA, might be a prospective intervention for anti-obesity in a preclinical setting. &#xa9; 2024 Society of Chemical Industry.}, }
@article {pmid39029231, year = {2024}, author = {Du, HX and Yue, SY and Niu, D and Liu, XH and Li, WY and Wang, X and Chen, J and Hu, DK and Zhang, LG and Guan, Y and Ji, DX and Chen, XG and Zhang, L and Liang, CZ}, title = {Alcohol intake exacerbates experimental autoimmune prostatitis through gut microbiota driving cholesterol biosynthesis-mediated Th17 differentiation.}, journal = {International immunopharmacology}, volume = {139}, number = {}, pages = {112669}, doi = {10.1016/j.intimp.2024.112669}, pmid = {39029231}, issn = {1878-1705}, mesh = {Animals ; Male ; *Th17 Cells/immunology ; *Prostatitis/immunology/microbiology/metabolism/chemically induced ; *Gastrointestinal Microbiome/drug effects/immunology ; *Autoimmune Diseases/immunology/chemically induced ; Mice ; *Cell Differentiation/drug effects ; *Mice, Inbred C57BL ; *Disease Models, Animal ; *Alcohol Drinking/adverse effects ; *Cholesterol/metabolism ; Sterol Regulatory Element Binding Protein 2/metabolism/genetics ; }, abstract = {BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is very common worldwide, and alcohol consumption is a notable contributing factor. Researches have shown that gut microbiota can be influenced by alcohol consumption and is an important mediator in regulating Th17 cell immunity. However, it is still unclear the exact mechanism by which alcohol exacerbates the CP/CPPS and the role of gut microbiota in this process.<br><br>METHOD: We first constructed the most-commonly used animal model for CP/CPPS, the experimental autoimmune prostatitis (EAP) model, through immunoassay. Based on this, mice were divided into EAP group and alcohol-consuming EAP group. By 16S rRNA sequencing and non-targeted metabolomics analysis, differential gut microbiota and their metabolites between the two groups were identified. Subsequently, metabolomics detection targeting cholesterols was carried out to identify the exact difference in cholesterol. Furthermore, multiple methods such as flow cytometry and immunohistochemistry were used to detect the differentiation status of Th17 cells and severity of prostatitis treated with 27-hydroxycholesterol (the differential cholesterol) and its upstream regulatory factor-sterol regulatory element-binding protein 2 (SREBP2). Lastly, fecal transplantation was conducted to preliminary study on whether alcohol intake exacerbates EAP in immune receptor mice.<br><br>RESULTS: Alcohol intake increased the proportion of Th17 cells and levels of related inflammatory factors. It also led to an altered gut bacterial richness and increased gut permeability. Further metabolomic analysis showed that there were significant differences in a variety of metabolites between EAP and alcohol-fed EAP mice. Metabolic pathway enrichment analysis showed that the pathways related to cholesterol synthesis and metabolism were significantly enriched, which was subsequently confirmed by detecting the expression of metabolic enzymes. By targeting cholesterol synthesis, 27-hydroxycholesterol was significantly increased in alcohol-fed EAP mice. Subsequent mechanistic research showed that supplementation with 27-hydroxycholesterol could aggravate EAP and promote Th17 cell differentiation both in vivo and in vitro, which is regulated by SREBP2. In addition, we observed that fecal transplantation from mice with alcohol intake aggravated EAP in immunized recipient mice fed a normal diet.<br><br>CONCLUSION: Our study is the first to show that alcohol intake promotes Th17 cell differentiation and exacerbates EAP through microbiota-derived cholesterol biosynthesis.}, }
@article {pmid39027904, year = {2024}, author = {Li, Y and Zhang, B and Jiang, L and Cheng, T and Cheng, H and Qian, P}, title = {Gut microbiota plays pivotal roles in benign and malignant hematopoiesis.}, journal = {Blood science (Baltimore, Md.)}, volume = {6}, number = {4}, pages = {e00200}, pmid = {39027904}, issn = {2543-6368}, abstract = {Accumulated evidence emerges that dynamic changes in human gut microbiota and microbial metabolites can alter the ecological balance of symbiotic hosts. The gut microbiota plays a role in various diseases through different mechanisms. More and more attention has been paid to the effects that human microbiota extends beyond the gut. This review summarized the current understanding of the roles that gut microbiota plays in hematopoietic regulation and the occurrence and development of benign and malignant hematologic diseases. The progress of the application of microbiota in treatment was discussed in order to provide new insights into clinical diagnosis and treatment in the future.}, }
@article {pmid39027446, year = {2024}, author = {Khaledi, M and Sameni, F and Gholipour, A and Shahrjerdi, S and Golmohammadi, R and Gouvarchin Ghaleh, HE and Poureslamfar, B and Hemmati, J and Mobarezpour, N and Milasi, YE and Rad, F and Mehboodi, M and Owlia, P}, title = {Potential role of gut microbiota in major depressive disorder: A review.}, journal = {Heliyon}, volume = {10}, number = {12}, pages = {e33157}, pmid = {39027446}, issn = {2405-8440}, abstract = {Interactions between the gut microbiota and host immunity are sophisticated, dynamic, and host-dependent. Scientists have recently conducted research showing that disturbances in the gut bacterial community can lead to a decrease in some metabolites and, consequently, to behaviors such as depression. Exposure to stressors dropped the relative abundance of bacteria in the genus Bacteroides while soaring the relative abundance of bacteria in the genus Clostridium, Coprococcus, Dialister, and Oscillibacter, which were also reduced in people with depression. Microbiota and innate immunity are in a bilateral relationship. The gut microbiota has been shown to induce the synthesis of antimicrobial proteins such as catalysidins, type C lectins, and defensins. Probiotic bacteria can modulate depressive behavior through GABA signaling. The gut microbiome produces essential metabolites such as neurotransmitters, tryptophan metabolites, and short-chain fatty acids (SCFAs) that can act on the CNS. In the case of dysbiosis, due to mucin changes, the ratio of intestinal-derived molecules may change and contribute to depression. Psychotropics, including Bifidobacterium longum NCC3001, Clostridium butyricum CBM588, and Lactobacillus acidophilus, have mental health benefits, and can have a positive effect on the host-brain relationship, and have antidepressant effects. This article reviews current studies on the association between gut microbiota dysbiosis and depression. Comprehensively, these findings could potentially lead to novel approaches to improving depressive symptoms via gut microbiota alterations, including probiotics, prebiotics, and fecal microbiota transplantation.}, }
@article {pmid39027096, year = {2024}, author = {Cui, X and Wu, Z and Zhou, Y and Deng, L and Chen, Y and Huang, H and Sun, X and Li, Y and Wang, H and Zhang, L and He, J}, title = {A bibliometric study of global trends in T1DM and intestinal flora research.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1403514}, pmid = {39027096}, issn = {1664-302X}, abstract = {BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that seriously jeopardizes human physical and mental health and reduces quality of life. Intestinal flora is one of the critical areas of exploration in T1DM research.<br><br>OBJECTIVE: This study aims to explore the research hotspot and development trend of T1DM and intestinal flora to provide research direction and ideas for researchers.<br><br>METHODS: We used the Web of Science (WOS) Core Collection and searched up to 18 November 2023, for articles on studies of the correlation between T1DM and intestinal flora. CiteSpace, VOSviewers and R package "bibliometrix" were used to conduct this bibliometric analysis.<br><br>RESULTS: Eventually, 534 documents met the requirements to be included, and as of 18 November 2023, there was an upward trend in the number of publications in the field, with a significant increase in the number of articles published after 2020. In summary, F Susan Wong (UK) was the author with the most publications (21), the USA was the country with the most publications (198), and the State University System of Florida (the United States) was the institution with the most publications (32). The keywords that appeared more frequently were T cells, fecal transplants, and short-chain fatty acids. The results of keywords with the most robust citation bursts suggest that Faecalibacterium prausnitzii and butyrate may become a focus of future research.<br><br>CONCLUSION: In the future, intestinal flora will remain a research focus in T1DM. Future research can start from Faecalibacterium prausnitzii and combine T cells, fecal bacteria transplantation, and short-chain fatty acids to explore the mechanism by which intestinal flora affects blood glucose in patients with T1DM, which may provide new ideas for the prevention and treatment of T1DM.}, }
@article {pmid39026673, year = {2024}, author = {Chen, Y and Sun, K and Qi, Y and Tang, J and Zhu, H and Wang, Z}, title = {L-valine derived from the gut microbiota protects sepsis-induced intestinal injury and negatively correlates with the severity of sepsis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1424332}, pmid = {39026673}, issn = {1664-3224}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Sepsis/microbiology ; Animals ; Mice ; Humans ; *Valine/pharmacology/therapeutic use ; Male ; Female ; Middle Aged ; Fecal Microbiota Transplantation ; Severity of Illness Index ; Metabolomics/methods ; Aged ; Feces/microbiology ; Disease Models, Animal ; Mice, Inbred C57BL ; Intestinal Mucosa/metabolism/microbiology ; Intestines/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The protective role of gut microbiota and its metabolites against intestinal damage in sepsis patients remain unclear.<br><br>METHODS: Fecal samples were acquired from patients categorized into sepsis and non-sepsis groups for analysis of microbial composition via 16S rRNA sequencing and untargeted metabolomics analysis. We assessed the impact of gut microbiota from sepsis patients on intestinal barriers in antibiotic-treated mice. Furthermore, We conducted spearman's correlation analysis to examine the relationship between metabolites and the severity of sepsis. Additionally, we performed animal experiments to validate the functionality of identified metabolites.<br><br>RESULTS: The diversity of intestinal flora is decreased in patients with sepsis compared to the control group. Through fecal microbiota transplantation experiments, it was discovered that the gut microbiota derived from sepsis patients could induce intestinal damage in antibiotic-treated mice. Metabolomics analysis of the microbiota revealed a significant enrichment of the Valine, leucine, and isoleucine biosynthesis pathway. Further analysis showed a significant decrease in the abundance of L-valine in sepsis patients, which was negatively correlated with APACHE-II and SOFA scores. In sepsis mouse experiments, it was found that L-valine could alleviate sepsis-induced intestinal damage.<br><br>CONCLUSION: Alterations in microbial and metabolic features in the gut can affect the severity of sepsis. Furthermore, L-valine can protect against sepsis-induced intestinal injury.}, }
@article {pmid39026313, year = {2024}, author = {Tian, X and Li, S and Wang, C and Zhang, Y and Feng, X and Yan, Q and Guo, R and Wu, F and Wu, C and Wang, Y and Huo, X and Ma, X}, title = {Gut virome-wide association analysis identifies cross-population viral signatures for inflammatory bowel disease.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {130}, pmid = {39026313}, issn = {2049-2618}, support = {82225048 and 82370563//National Natural Science Foundation of China/ ; 82225048 and 82370563//National Natural Science Foundation of China/ ; 2019RD15 and 2022RY18//Dalian Science and Technology Leading Talents Project/ ; 2019RD15 and 2022RY18//Dalian Science and Technology Leading Talents Project/ ; XLYC2002008//Distinguished professor of Liaoning Province/ ; }, mesh = {Humans ; *Virome ; *Gastrointestinal Microbiome/genetics ; Animals ; *Feces/virology/microbiology ; Mice ; *Inflammatory Bowel Diseases/virology/microbiology ; Female ; Male ; Adult ; Middle Aged ; Crohn Disease/virology/microbiology ; Bacteriophages/genetics/isolation &amp; purification ; Colitis, Ulcerative/virology/microbiology ; Bacteria/classification/genetics/isolation &amp; purification ; China ; Fecal Microbiota Transplantation ; Case-Control Studies ; Viruses/classification/isolation &amp; purification/genetics ; }, abstract = {BACKGROUND: The gut virome has been implicated in inflammatory bowel disease (IBD), yet a full understanding of the gut virome in IBD patients, especially across diverse geographic populations, is lacking.<br><br>RESULTS: In this study, we conducted a comprehensive gut virome-wide association study in a Chinese cohort of 71 IBD patients (15 with Crohn's disease and 56 with ulcerative colitis) and 77 healthy controls via viral-like particle (VLP) and bulk virome sequencing of their feces. By utilizing an integrated gut virus catalog tailored to the IBD virome, we revealed fundamental alterations in the gut virome in IBD patients. These characterized 139 differentially abundant viral signatures, including elevated phages predicted to infect Escherichia, Klebsiella, Enterococcus_B, Streptococcus, and Veillonella&#xa0;species, as well as IBD-depleted phages targeting Prevotella, Ruminococcus_E, Bifidobacterium, and Blautia species. Remarkably, these viral signatures demonstrated high consistency across diverse populations such as those in Europe and the USA, emphasizing their significance and broad relevance in the disease context. Furthermore, fecal virome transplantation experiments verified that the colonization of these IBD-characterized viruses can modulate experimental colitis in mouse models.<br><br>CONCLUSIONS: Building upon these insights into the IBD gut virome, we identified potential biomarkers for prognosis and therapy in IBD patients, laying the foundation for further exploration of viromes in related conditions. Video Abstract.}, }
@article {pmid39023942, year = {2024}, author = {Yirmiya, K and Turjeman, S and Shtossel, O and Zagoory-Sharon, O and Moadi, L and Rubin, E and Sharon, E and Louzoun, Y and Koren, O and Feldman, R}, title = {Microbiome signature of posttraumatic stress disorder and resilience in youth.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {}, number = {}, pages = {}, doi = {10.1037/tra0001727}, pmid = {39023942}, issn = {1942-969X}, support = {//Bezos Family Foundation/ ; //theHarris Corporation/ ; //European Research Council (ERC)/ ; //Azrieli Foundation/ ; }, abstract = {OBJECTIVE: Identifying biomarkers that can distinguish trauma-exposed youth at risk for developing posttraumatic pathology from resilient individuals is essential for targeted interventions. As trauma can alter the microbiome with lasting effects on the host, our longitudinal, multimeasure, cross-species study aimed to identify the microbial signature of posttraumatic stress disorder (PTSD).<br><br>METHOD: We followed children exposed to war-related trauma and matched controls from early childhood (Mage = 2.76 years, N = 232) to adolescence (Mage = 16.13 years, N = 84), repeatedly assessing posttraumatic symptomatology and maternal caregiving. In late adolescence, we collected fecal samples from mothers and youth and assessed microbiome composition, diversity, and mother-child microbial synchrony. We then transplanted adolescents' fecal samples into germ-free mice to determine if behavioral changes are observed.<br><br>RESULTS: Youth with PTSD exhibited a distinct gut microbiome profile and lower diversity compared to resilient individuals, and microbiome diversity mediated the continuity of posttraumatic symptomatology throughout development. Low microbiome diversity correlated with more posttraumatic symptoms in early childhood, more emotional and behavioral problems in adolescence, and poor maternal caregiving. Youth with PTSD demonstrated less mother-child microbial synchrony, suggesting that low microbial concordance between mother and child may indicate susceptibility to posttraumatic illness. Germ-free mice transplanted with microbiomes from individuals with PTSD displayed increased anxious behavior.<br><br>CONCLUSIONS: Our findings provide evidence that the trauma-associated microbiome profile is at least partially responsible for the anxiety component of the PTSD phenotype and highlight microbial underpinnings of resilience. Further, our results suggest that the microbiome may serve as additional biological memory of early life stress and underscore the potential for microbiome-related diagnosis and treatment following trauma. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, }
@article {pmid39022481, year = {2024}, author = {Beyer, BR and Sheppard, C and Mullins, J and Igbadumhe, A}, title = {Campylobacter Infection Introduced Following Fecal Microbiota Transplantation.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62541}, pmid = {39022481}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation is an evidence-based therapeutic option for recurrent Clostridium difficile infection, involving the transfer of healthy donor fecal material to restore gut microbial balance. Despite meticulous donor screening, Campylobacter jejuni, a prevalent cause of bacterial gastroenteritis, is not routinely tested, potentially impacting fecal microbiota transplant safety. We present a case of a female with recurrent C. difficile infection treated with fecal microbiota transplantation, complicated by a subsequent C. jejuni infection. The emergence of Campylobacter post fecal microbiota transplantation underscores the importance of comprehensive donor screening protocols. Our case prompts a reevaluation of fecal microbiota transplantation safety measures and advocates for inclusive screening to enhance patient outcomes.}, }
@article {pmid39021924, year = {2024}, author = {Xu, D and Ren, L and Zhang, W and Wu, S and Yu, M and He, X and Wei, Z}, title = {Therapeutic effects and mechanisms of fecal microbiota transplantation on EAE partly through HPA axis-mediated neuroendocrine regulation.}, journal = {Heliyon}, volume = {10}, number = {12}, pages = {e33214}, pmid = {39021924}, issn = {2405-8440}, abstract = {BACKGROUND: The pathogenesis of multiple sclerosis (MS) may be closely related to immune regulation and inflammatory cytokines induced by specific flora. Repairing the intestinal flora may alter the immune response in MS patients, thus opening up novel approaches for the treatment of MS.<br><br>OBJECTIVE: We aimed to test the therapeutic effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and the characteristics of intestinal microbiota composition changes, explore the potential mechanisms of FMT treatment.<br><br>METHODS: EAE animals were treated with FMT, with the therapeutic effects were evaluated by observing neurological scores and measuring serum levels of cortisol, IL-17, and TLR-2. Fecal microbiome 16S rRNA sequencing was used to profile changes in microbiota composition, and adrenalectomy pretreatment was used to test whether FMT effects were dependent on HPA axis function.<br><br>RESULTS: FMT improved neurological function and reduced serum IL-17 to levels that were close to the control group. FMT reestablished intestinal homeostasis by altering the structure of the intestinal flora, increasing the abundance of beneficial flora, and regulating intestinal metabolites. We found that the therapeutic effects of FMT depended partly on the efferent function of the HPA axis; surgical disruption of the HPA axis altered the abundance and diversity of the intestinal flora.<br><br>CONCLUSION: FMT showed a neuroprotective effect on EAE by increasing the abundance of the beneficial flora, rebuilding intestinal homeostasis, reducing IL-17 and cortisol serum levels, and promoting serum TLR-2; the therapeutic effect of FMT on EAE is partly dependent on the HPA axis.}, }
@article {pmid39021516, year = {2024}, author = {Xu, J and Xu, H and Yang, F and Xie, Y and Cai, F and Mao, S and Lu, M and Zhuang, H and Hua, ZC}, title = {Different depths of food restriction and high-fat diet refeeding in mice impact host obesity and metabolic phenotypes with correlative changes in the gut microbiota.}, journal = {MedComm}, volume = {5}, number = {8}, pages = {e641}, pmid = {39021516}, issn = {2688-2663}, abstract = {Overweight and obesity affect almost 2 billion adults worldwide, and food restriction (FR) is commonly used to reduce body fat. Whether refeeding (Re) after FR at different ages and to different degrees leads to overweight and its possible mechanisms are uncertain. In this study, adult and young mice were both restricted to 15% and 40% of their casual food intake, and then were fed 60% high-fat chow (FR15%-Re, FR40%-Re), whereas the control groups(CON) consumed high-fat or normal food throughout, respectively. The results of the study suggest that mild FR-heavy feeding may lead to more significant abnormal fat accumulation, liver damage, and increased recruitment of intestinal inflammatory factors and immune cells in mice of different ages and involves multiple types of alterations in the gut microbiota. Further fecal transplantation experiments as well as serum and liver enzyme-linked immunosorbent assay experiments preliminarily suggest that the link between lipid metabolism and inflammatory responses and the gut microbiota may be related to the regulation of the gut and live by Lipopolysaccharides(LPS) and Peroxisome Proliferator-Activated Receptor-Alpha(PPAR-α). In addition, our study may also serve as a reference for studying obesity prevention and treatment programs at different ages.}, }
@article {pmid39017661, year = {2024}, author = {Rashidi, A and Pidala, J and Hamilton, BK and Pavletic, SZ and Kim, K and Zevin, A and Mays, JW and Lee, SJ}, title = {Oral and Gut Microbiome Alterations in Oral Chronic GVHD Disease: Results from Close Assessment and Testing for Chronic GVHD (CATCH Study).}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {30}, number = {18}, pages = {4240-4250}, pmid = {39017661}, issn = {1557-3265}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; U01 CA236229/CA/NCI NIH HHS/United States ; ZIA DE000747/ImNIH/Intramural NIH HHS/United States ; U01 CA118953/CA/NCI NIH HHS/United States ; CA118953//National Cancer Institute (NCI)/ ; CA236229//National Institute of Dental and Craniofacial Research (NIDCR)/ ; R01 CA118953/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Graft vs Host Disease/microbiology/diagnosis ; *Gastrointestinal Microbiome ; Female ; Male ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Middle Aged ; Adult ; Chronic Disease ; *Mouth/microbiology ; Transplantation, Homologous ; Aged ; Feces/microbiology ; Prospective Studies ; Metagenomics/methods ; Young Adult ; }, abstract = {PURPOSE: Whether and how the oral microbiome and its changes in allogeneic hematopoietic cell transplantation (alloHCT) recipients may contribute to oral chronic GVHD (cGVHD) pathogenesis is unknown. In addition, although the oral and colonic microbiota are distinct in healthy adults, whether oral microbes may ectopically colonize the gut in alloHCT patients is unknown.<br><br>EXPERIMENTAL DESIGN: To address these knowledge gaps, longitudinal oral and fecal samples were collected prospectively in the multicenter Close Assessment and Testing for Chronic GVHD study (NCT04188912). Through shotgun metagenomic sequencing of the samples collected at baseline, oral cGVHD onset, first post-cGVHD onset visit, and 1-year post-HCT time points in patients with oral cGVHD (cases; N = 29) or without any cGVHD (controls; N = 51), we examined whether (i) oral and/or gut microbiomes and their longitudinal trajectories differ between cases and controls and (ii) oral and gut microbiomes overlap in alloHCT recipients, especially those developing cGVHD.<br><br>RESULTS: A total of 195 samples were analyzed. The onset of oral cGVHD was characterized by an expansion of Streptococcus salivarius and Veillonella parvula in the oral microbiome. High levels of oral/gut microbiota overlap were observed, particularly in patients with oral cGVHD, suggesting ectopic colonization of the gut by oral bacteria.<br><br>CONCLUSIONS: The unusual coalescence of two distant niches in these patients may result in short- or long-term consequences for the host, a novel avenue for future research. In addition, this study suggests a contribution of the oral microbiome to oral cGVHD pathogenesis.}, }
@article {pmid39012957, year = {2024}, author = {Zhao, S and Zhang, H and Zhu, H and Zhao, T and Tu, J and Yin, X and Yang, S and Zhang, W and Zhang, F and Zhang, M and Xu, B and Zhuge, Y and Xiao, J}, title = {Gut microbiota promotes macrophage M1 polarization in hepatic sinusoidal obstruction syndrome via regulating intestinal barrier function mediated by butyrate.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2377567}, pmid = {39012957}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Butyrates/metabolism ; *Macrophages/immunology ; Male ; Humans ; *Fecal Microbiota Transplantation ; *Hepatic Veno-Occlusive Disease/microbiology ; *Disease Models, Animal ; *Liver/metabolism ; Macrophage Activation ; Mice, Inbred C57BL ; Intestinal Mucosa/microbiology ; Female ; Feces/microbiology ; Bacteria/classification/isolation &amp; purification/genetics ; Intestinal Barrier Function ; }, abstract = {BACKGROUND: The intestinal-liver axis is associated with various liver diseases. Here, we verified the role of the gut microbiota and macrophage activation in the progression of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS), and explored the possible mechanisms and new treatment options.<br><br>METHODS: The HSOS murine model was induced by gavage of monocrotaline (MCT). An analysis of 16S ribosomal DNA (16S rDNA) of the feces was conducted to determine the composition of the fecal microbiota. Macrophage clearance, fecal microbiota transplantation (FMT), and butyrate supplementation experiments were used to assess the role of intestinal flora, gut barrier, and macrophage activation and to explore the relationships among these three variables.<br><br>RESULTS: Activated macrophages and low microflora diversity were observed in HSOS patients and murine models. Depletion of macrophages attenuated inflammatory reactions and apoptosis in the mouse liver. Moreover, compared with control-FMT mice, the exacerbation of severe liver injury was detected in HSOS-FMT mice. Specifically, butyrate fecal concentrations were significantly reduced in HSOS mice, and administration of butyrate could partially alleviated liver damage and improved the intestinal barrier in vitro and in vivo. Furthermore, elevated lipopolysaccharides in the portal vein and high proportions of M1 macrophages in the liver were also detected in HSOS-FMT mice and mice without butyrate treatment, which resulted in severe inflammatory responses and further accelerated HSOS progression.<br><br>CONCLUSIONS: These results suggested that the gut microbiota exacerbated HSOS progression by regulating macrophage M1 polarization via altered intestinal barrier function mediated by butyrate. Our study has identified new strategies for the clinical treatment of HSOS.}, }
@article {pmid39012675, year = {2024}, author = {Cheng, CK and Gao, J and Kang, L and Huang, Y}, title = {Fecal Microbiota Transfer from Young Mice Reverts Vascular Aging Hallmarks and Metabolic Impairments in Aged Mice.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.0384}, pmid = {39012675}, issn = {2152-5250}, abstract = {As a major risk factor for cardiometabolic diseases, aging refers to a gradual decline in physiological function, characterized with 12 conspicuous hallmarks, like telomere attrition, chronic inflammation, and dysbiosis. Common vascular aging hallmarks include endothelial dysfunction, telomere dysfunction, and vascular inflammation. In this study, we sought to test the hypothesis that young-derived gut microbiota retards vascular aging hallmarks and metabolic impairments in aged hosts. We also aimed to study the therapeutic efficacy of young microbiota in hosts of different ages. Fecal microbiota transplantation (FMT) from young to aged or middle-aged C57BL/6 mice was conducted for 6 consecutive weeks after antibiotic pretreatment. Endothelium-dependent relaxations (EDRs) in mouse arteries were determined by wire myography. Inflammation and AMPK/SIRT1 signaling in mouse aortas and intestines were studied by biochemical assays. The telomere function of aortas and intestines, in terms of telomerase reverse transcriptase expression, telomerase activity, and relative telomere length, were also studied. FMT significantly reverted vascular dysfunction and metabolic impairments in middle-aged mice than in aged mice. Besides, FMT significantly reverted inflammation and telomere dysfunction in aortas and intestines of middle-aged mice. Improved intestinal barrier function and activated AMPK/SIRT1 signaling potentially underlie benefits of FMT. The findings imply gut-vascular connection as potential target against age-associated cardiometabolic disorders, highlight crosstalk among aging hallmarks, and suggest a critical timepoint for efficacy of anti-aging interventions.}, }
@article {pmid39012524, year = {2024}, author = {Tian, YQ and Ren, X and Wang, J and Li, X and Yin, YS and Guo, ZH and Qin, ZL and Zeng, XY}, title = {Berberine hydrochloride alleviates chronic prostatitis/chronic pelvic pain syndrome by modifying gut microbiome signaling.}, journal = {Asian journal of andrology}, volume = {26}, number = {5}, pages = {500-509}, pmid = {39012524}, issn = {1745-7262}, mesh = {*Berberine/pharmacology/therapeutic use ; Male ; Animals ; *Prostatitis/microbiology/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Rats, Sprague-Dawley ; *Signal Transduction/drug effects ; Pelvic Pain/drug therapy/therapy ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Oxidative Stress/drug effects ; Chronic Pain/drug therapy ; Prostate/drug effects/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is highly prevalent worldwide and poses a significant threat to men's health, particularly affecting young men. However, the exact causes and mechanisms behind CP/CPPS remain unclear, leading to challenges in its treatment. In this research, a CP/CPPS rat model was established with complete Freund's adjuvant (CFA), and berberine hydrochloride was administered through daily gavage to assess its therapeutic effects. The alterations in the gut microbiome induced by CP/CPPS and berberine hydrochloride were investigated through 16S ribosomal RNA sequencing of cecum content and colonic epithelial cells. To investigate the impact of the gut microbiome on CP/CPPS, a pseudo germ-free rat model was established, and fecal microbiome transplantation (FMT) was performed on these rats. In all, berberine hydrochloride demonstrated effective reduction of inflammation and oxidative stress in the prostate, offering significant therapeutic advantages for CP/CPPS. Through analysis of the gut microbiome using 16S ribosome RNA sequencing, distinct differences were observed between CP/CPPS rats and control rats, and Clostridium butyricum was identified as a key bacteria. Pseudo germ-free rats that underwent FMT from CP/CPPS rats or rats treated with berberine hydrochloride displayed varying levels of inflammatory cytokine production, oxidative stress, and activity of associated signaling pathways. In conclusion, the therapeutic potential of berberine hydrochloride in addressing CP/CPPS is highly significant. The gut microbiome has emerged as a critical factor in the development of CP/CPPS and plays a pivotal role in mediating the therapeutic effects of berberine hydrochloride.}, }
@article {pmid39009513, year = {2024}, author = {Shoji, F}, title = {[The Role of Gut Microbiota in Lung Carcinogenesis and Cancer Immunotherapy].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {51}, number = {6}, pages = {597-602}, pmid = {39009513}, issn = {0385-0684}, mesh = {Animals ; Humans ; Carcinogenesis/immunology ; Dysbiosis/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Lung Neoplasms/immunology/therapy/microbiology ; }, abstract = {In recent years, the human microbiota, especially the gut microbiota, has been attracting attention in various fields, and it is one of the topics in the field of oncology. The human microbiota is known to act directly or indirectly on host immunity, and the gut and lung microbiota influence each other through the"gut-lung axis". It has been suggested that dysbiosis, a condition in which the symbiosis of the human microbiota is disrupted, induces lung inflammation and various respiratory diseases, and is also implicated in the immune microenvironment of lung cancer. It is also widely known that the gut microbiota modulates the efficacy of cancer immunotherapy, a major pillar of lung cancer treatment, and many clinical trials targeting the gut microbiota, such as fecal microbiome transplantation and biotics intervention, are currently being conducted. In the future, research on lung carcinogenesis mechanisms and lung cancer treatment focusing on the human microbiota will become increasingly active.}, }
@article {pmid39009231, year = {2024}, author = {Réthi-Nagy, Z and Juhász, S}, title = {Microbiome's Universe: Impact on health, disease and cancer treatment.}, journal = {Journal of biotechnology}, volume = {392}, number = {}, pages = {161-179}, doi = {10.1016/j.jbiotec.2024.07.002}, pmid = {39009231}, issn = {1873-4863}, mesh = {Humans ; *Neoplasms/therapy/microbiology ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Dysbiosis/microbiology/therapy ; Microbiota ; Animals ; }, abstract = {The human microbiome is a diverse ecosystem of microorganisms that reside in the body and influence various aspects of health and well-being. Recent advances in sequencing technology have brought to light microbial communities in organs and tissues that were previously considered sterile. The gut microbiota plays an important role in host physiology, including metabolic functions and immune modulation. Disruptions in the balance of the microbiome, known as dysbiosis, have been linked to diseases such as cancer, inflammatory bowel disease and metabolic disorders. In addition, the administration of antibiotics can lead to dysbiosis by disrupting the structure and function of the gut microbial community. Targeting strategies are the key to rebalancing the microbiome and fighting disease, including cancer, through interventions such as probiotics, fecal microbiota transplantation (FMT), and bacteria-based therapies. Future research must focus on understanding the complex interactions between diet, the microbiome and cancer in order to optimize personalized interventions. Multidisciplinary collaborations are essential if we are going to translate microbiome research into clinical practice. This will revolutionize approaches to cancer prevention and treatment.}, }
@article {pmid39006746, year = {2024}, author = {Luo, C and Li, S and Chen, T}, title = {Editorial: The role of probiotics, postbiotics, and microbial metabolites in preventing and treating chronic diseases, volume II.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1442855}, pmid = {39006746}, issn = {2235-2988}, mesh = {*Probiotics/therapeutic use ; Humans ; Chronic Disease/prevention &amp; control ; Gastrointestinal Microbiome ; }, }
@article {pmid39006586, year = {2024}, author = {Sanzone, J and Life, M and Reiss, D and May, D and Hartley, B and Spiddle, P and Al-Kirwi, J and Grigoryan, T and Costin, J}, title = {Uses of Fecal Microbiota Transplantation in Neurodegenerative Disease: A Scoping Review.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62265}, pmid = {39006586}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) is the administration of fecal bacteria from a healthy donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition and confer a health benefit. The relationship between the gut microbiome and the central nervous system, termed the gut-brain axis, has been a frequent topic of gut microbiome studies. Commensal gut bacteria communicate with the central nervous system through various hormones, cytokines, and neural pathways. Therefore, influencing the gut microbiome via FMT may have the potential in treating symptoms of neurodegenerative conditions. This study aims to identify current uses of FMT in treating neurodegenerative diseases and highlight areas of future investigation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, a literature search was conducted of peer-reviewed sources on September 27, 2022, from Embase, MEDLINE, Web of Science, and Cochrane Central. Search terms were utilized that were related to the application of FMT and neurodegenerative disorders and limited those human studies, those that were published in English, and those that were published between 2017 and 2022. The initial search yielded 450 unique articles, and after the assessment of the title and abstract for inclusion and exclusion criteria, six articles were identified for full-text review. Studies that focused on either Parkinson's disease (PD) or multiple sclerosis (MS) demonstrated improvements in both motor symptoms and non-motor symptoms. FMT was also shown to provide significant relief of constipation and general gastrointestinal (GI) symptoms in all conditions studied. The studies related to MS showed the most mixed results with regard to symptomatic improvement. The data on the use of FMT as a treatment for neurodegenerative disorders is limited; however, studies have shown not only improvement in GI symptoms but also improvement in the cognitive symptoms of PD and dementia. The data on FMT as a treatment to improve the motor symptoms of PD is both more complete and more compelling than the data on the motor symptoms of MS. The studies that were reviewed showed no major adverse effects of FMT and generally promising results. There is a strong case to be made for larger, more well-controlled studies to be done on FMT and its potential use as a treatment not only for GI symptoms but for the motor and cognitive symptoms of neurodegenerative diseases.}, }
@article {pmid39006502, year = {2024}, author = {Lee, CS and Lin, CR and Chua, HH and Wu, JF and Chang, KC and Ni, YH and Chang, MH and Chen, HL}, title = {Gut Bifidobacterium longum is associated with better native liver survival in patients with biliary atresia.}, journal = {JHEP reports : innovation in hepatology}, volume = {6}, number = {7}, pages = {101090}, pmid = {39006502}, issn = {2589-5559}, abstract = {BACKGROUND &amp; AIMS: The gut microbiome plays an important role in liver diseases, but its specific impact on biliary atresia (BA) remains to be explored. We aimed to investigate the microbial signature in the early life of patients with BA and to analyze its influence on long-term outcomes.<br><br>METHODS: Fecal samples (n&#xa0;= 42) were collected from infants with BA before and after Kasai portoenterostomy (KPE). The stool microbiota was analyzed using 16S rRNA next-generation sequencing and compared with that of age-matched healthy controls (HCs). Shotgun metagenomic sequencing analysis was employed to confirm the bacterial composition in 10 fecal samples before KPE. The correlation of the microbiome signature with liver function and long-term outcomes was assessed.<br><br>RESULTS: In the 16S rRNA next-generation sequencing analysis of fecal microbiota, the alpha and beta diversity analyses revealed significant differences between HCs and patients with BA before and after KPE. The difference in microbial composition analyzed by linear discriminant analysis and random forest classification revealed that the abundance of Bifidobacterium longum (B.&#xa0;longum) was significantly lower in patients before and after KPE than in HCs. The abundance of B.&#xa0;longum was negatively correlated with the gamma-glutamyltransferase level after KPE (p <0.05). Patients with early detectable B. longum had significantly lower total and direct bilirubin 3 months after KPE (p <0.005) and had a significantly lower liver transplantation rate (hazard ratio: 0.16, 95% CI 0.03-0.83, p&#xa0;= 0.029). Shotgun metagenomic sequencing also revealed that patients with BA and detectable B. longum had reduced total and direct bilirubin after KPE.<br><br>CONCLUSION: The gut microbiome of patients with BA differed from that of HCs, with a notable abundance of B.&#xa0;longum in early infancy correlating with better long-term outcomes.<br><br>IMPACT AND IMPLICATIONS: Bifidobacterium longum (B.&#xa0;longum) is a beneficial bacterium commonly found in the human gut. It has been studied for its potential impacts on various health conditions. In patients with biliary atresia, we found that a greater abundance of B.&#xa0;longum in the fecal microbiome is associated with improved clinical outcomes. This suggests that early colonization and increasing B.&#xa0;longum levels in the gut could be a therapeutic strategy to improve the prognosis of patients with biliary atresia.}, }
@article {pmid39006130, year = {2024}, author = {Mao, Q and Wang, X and Cai, H and Yang, J and Zhang, Y and Min, W and Qian, Q and Zeng, Y}, title = {Research Progress on the Correlation of Atopic Dermatitis with Gut Microbiota.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {17}, number = {}, pages = {1613-1619}, pmid = {39006130}, issn = {1178-7015}, abstract = {Atopic dermatitis (AD) is a common skin disease, the pathogenesis of which has not been fully elucidated. The gut microbiota is the largest micro-ecosystem in the human body that affects the immune system and skin barrier function. Recent studies have shown that in addition to the environmental factors, skin barrier, genetic factors and immune response, gut microbiota disturbance may also cause AD. This review described the correlation of AD with gut microbiota and existing research status of AD treatment via targeting gut microbiota.}, }
@article {pmid39003673, year = {2024}, author = {Schrock, J and Yan, M and Dolatyabi, S and Patil, V and Yadagiri, G and Renu, S and Ramesh, A and Wood, R and Hanson, J and Yu, Z and Renukaradhya, GJ}, title = {Human Infant Fecal Microbiota Differentially Influences the Mucosal Immune Pathways Upon Influenza Infection in a Humanized Gnotobiotic Pig Model.}, journal = {Current microbiology}, volume = {81}, number = {9}, pages = {267}, pmid = {39003673}, issn = {1432-0991}, support = {2018//College of Food, Agricultural, and Environmental Sciences, Ohio State University/ ; }, mesh = {Animals ; Swine ; *Germ-Free Life ; *Feces/microbiology/virology ; Humans ; *Gastrointestinal Microbiome ; *Immunity, Mucosal ; *Influenza A Virus, H1N1 Subtype/immunology ; *Disease Models, Animal ; *Cytokines/metabolism ; Orthomyxoviridae Infections/immunology/virology ; Viral Load ; Infant ; Influenza, Human/immunology/microbiology/virology ; }, abstract = {In this study, we evaluated the impact of human gut microbiota on the immune pathways in the respiratory tract using a gnotobiotic (Gn) piglet model. We humanized piglets with rural and urban infant fecal microbiota (RIFM and UIFM, respectively) and then infected them with a H1N1 swine influenza virus. We analyzed the microbial diversity and structure of the intestinal and respiratory tracts of the piglets before and after the influenza virus infection and measured the viral load and immune responses. We found that the viral load in the upper respiratory tract of UIFM transplanted piglets was higher than their rural cohorts (RIFM), while virus-specific antibody responses were comparable. The relative cytokine gene expression in the tracheobronchial (respiratory tract) and mesenteric (gastrointestinal) lymph nodes, lungs, blood, and spleen of RIFM and UIFM piglets revealed a trend in reciprocal regulation of proinflammatory, innate, and adaptive immune-associated cytokines as well as the frequency of T-helper/memory cells, cytotoxic T cells, and myeloid immune cell subsets. We also observed different phylum-level shifts of the fecal microbiota in response to influenza virus infection between the two piglet groups, suggesting the potential impact of the gut microbiota on the immune responses to influenza virus infection and lung microbiota. In conclusion, Gn piglets humanized with diverse infant fecal microbiota had differential immune regulation, with UIFM favoring the activation of proinflammatory immune mediators following an influenza virus infection compared to their rural RIFM cohorts. Furthermore, Gn piglets can be a useful model in investigating the impact of diverse human microbiota of the gastrointestinal tract, probably also the respiratory tract, on respiratory health and testing specific probiotic- or prebiotic-based therapeutics.}, }
@article {pmid39002809, year = {2024}, author = {Liao, L and Zhang, L and Yang, C and Wang, T and Feng, L and Peng, C and Long, Y and Dai, G and Chang, L and Wei, Y and Fan, X}, title = {Sotagliflozin attenuates cardiac dysfunction and depression-like behaviors in mice with myocardial infarction through the gut-heart-brain axis.}, journal = {Neurobiology of disease}, volume = {199}, number = {}, pages = {106598}, doi = {10.1016/j.nbd.2024.106598}, pmid = {39002809}, issn = {1095-953X}, mesh = {Animals ; *Myocardial Infarction/drug therapy/complications ; Mice ; *Gastrointestinal Microbiome/drug effects/physiology ; *Depression/drug therapy ; Male ; *Mice, Inbred C57BL ; Brain-Gut Axis/drug effects/physiology ; Glycosides/pharmacology ; Fecal Microbiota Transplantation/methods ; Disease Models, Animal ; }, abstract = {Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001 were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.}, }
@article {pmid39000282, year = {2024}, author = {Lin, X and Han, H and Wang, N and Wang, C and Qi, M and Wang, J and Liu, G}, title = {The Gut Microbial Regulation of Epigenetic Modification from a Metabolic Perspective.}, journal = {International journal of molecular sciences}, volume = {25}, number = {13}, pages = {}, pmid = {39000282}, issn = {1422-0067}, support = {2022YFD1300403//National Key R&amp;D Program/ ; 2022JJ20027//Excellent Youth Foundation of Hunan Province/ ; CARS-35//Earmarked Fund for China Agriculture Research System/ ; }, mesh = {*Gastrointestinal Microbiome ; *Epigenesis, Genetic ; Humans ; *Obesity/metabolism/microbiology/genetics ; Animals ; Probiotics ; Fecal Microbiota Transplantation ; Prebiotics ; Energy Metabolism ; }, abstract = {Obesity is a global health challenge that has received increasing attention in contemporary research. The gut microbiota has been implicated in the development of obesity, primarily through its involvement in regulating various host metabolic processes. Recent research suggests that epigenetic modifications may serve as crucial pathways through which the gut microbiota and its metabolites contribute to the pathogenesis of obesity and other metabolic disorders. Hence, understanding the interplay between gut microbiota and epigenetic mechanisms is crucial for elucidating the impact of obesity on the host. This review primarily focuses on the understanding of the relationship between the gut microbiota and its metabolites with epigenetic mechanisms in several obesity-related pathogenic mechanisms, including energy dysregulation, metabolic inflammation, and maternal inheritance. These findings could serve as novel therapeutic targets for probiotics, prebiotics, and fecal microbiota transplantation tools in treating metabolic disruptions. It may also aid in developing therapeutic strategies that modulate the gut microbiota, thereby regulating the metabolic characteristics of obesity.}, }
@article {pmid38999862, year = {2024}, author = {Wu, Y and Li, Y and Zheng, Q and Li, L}, title = {The Efficacy of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.}, journal = {Nutrients}, volume = {16}, number = {13}, pages = {}, pmid = {38999862}, issn = {2072-6643}, support = {No. 2022ZFJH003//The Fundamental Research Funds for the Central Universities/ ; SYS202202//Shandong Provincial Laboratory Project/ ; }, mesh = {*Irritable Bowel Syndrome/therapy/microbiology ; Humans ; *Prebiotics/administration &amp; dosage ; *Probiotics/therapeutic use/administration &amp; dosage ; *Synbiotics/administration &amp; dosage ; *Fecal Microbiota Transplantation ; *Network Meta-Analysis ; Treatment Outcome ; Gastrointestinal Microbiome ; Randomized Controlled Trials as Topic ; Bifidobacterium ; Adult ; Female ; Lactobacillus ; Male ; }, abstract = {Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with gut microbiota imbalance playing a significant role. There are increasing numbers of research studies exploring treatment options involving probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), but it is still uncertain which treatment option is superior. The research was conducted on various databases and unpublished trial data (up to February 2023). Randomized controlled trials (RCTs) were screened for adult patients with IBS comparing interventions with placebo. Probiotics, prebiotics, synbiotics, and FMT were assessed for their impact using mean difference and Bayesian network meta-analysis. Out of 6528 articles, 54 were included for probiotics, 7 for prebiotics/synbiotics, and 6 for FMT. Probiotics showed improvement in IBS symptoms, particularly with Bifidobacterium and Lactobacillus strains. Prebiotics and synbiotics did not show significant improvement. Network meta-analysis indicated the favorable effects of probiotics (OR = 0.53, 95% CI, 0.48 to 0.59) and FMT (OR = 0.46, 95% CI, 0.33 to 0.64) on IBS, with no serious adverse events reported. In short, probiotics and FMT are effective for managing IBS, with Bifidobacterium and Lactobacillus being dominant strains. However, the most effective probiotic combination or strain remains unclear, while prebiotics and synbiotics did not show significant improvement.}, }
@article {pmid38997819, year = {2024}, author = {Gefen, R and Strassmann, V and Stefano Hernandez, F and Garoufalia, Z and Horesh, N and Emile, SH and Da Silva, G and Wexner, S}, title = {Risk factors for complications following sacral neuromodulation for faecal incontinence: Long-term follow-up.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {26}, number = {8}, pages = {1597-1607}, doi = {10.1111/codi.17092}, pmid = {38997819}, issn = {1463-1318}, mesh = {Humans ; *Fecal Incontinence/therapy/etiology ; Female ; Retrospective Studies ; Risk Factors ; Middle Aged ; Male ; *Postoperative Complications/etiology/epidemiology/therapy ; Follow-Up Studies ; *Electric Stimulation Therapy/methods/adverse effects ; Aged ; Adult ; Lumbosacral Plexus ; Treatment Outcome ; Sacrum/innervation ; }, abstract = {AIM: Sacral neuromodulation (SNM) has become a standard surgical treatment for faecal incontinence (FI). Prior studies have reported various adverse events of SNM, including suboptimal therapeutic response, infection, pain, haematoma, and potential need for redo SNM. The aim of this study was to identify the risk factors associated with long-term complications of SNM.<br><br>METHOD: This retrospective cohort reviewed patients who underwent two-stage SNM for FI at our institution between 2011-2021. Preoperative baseline characteristics and follow-up were obtained from the medical record and/or by telephone interview. Management and outcome of each postoperative event were evaluated by univariate and multivariate regression analyses.<br><br>RESULTS: A total of 291 patients (85.2% female) were included in this study. Postoperative complications were recorded in 219 (75.2%) patients and 154 (52.9%) patients required surgical intervention to treat complications. The most common postoperative event was loss of efficacy (46.4%). Other common adverse events were problems at the implant site (pain, infection, etc.) in 16.5% and pain during stimulation in 11.7%. Previous vaginal delivery (OR 2.74, p&#x2009;=&#x2009;0.003) and anal surgery (OR&#x2009;=&#x2009;2.46, p&#x2009;=&#x2009;0.039) were independent predictors for complications. Previous colorectal (OR&#x2009;=&#x2009;2.04, p&#x2009;=&#x2009;0.026) and anal (OR&#x2009;=&#x2009;1.98, p&#x2009;=&#x2009;0.022) surgery and history of irritable bowel syndrome (IBS) (OR&#x2009;=&#x2009;3.49, p&#x2009;=&#x2009;0.003) were independent predictors for loss of efficacy.<br><br>CONCLUSION: Postoperative adverse events are frequently recorded after SNM. Loss of efficacy is the most common. Previous colorectal or anal surgery, vaginal delivery, and IBS are independent risk factors for complications.}, }
@article {pmid38996677, year = {2024}, author = {Shao, W and Pan, B and Li, Z and Peng, R and Yang, W and Xie, Y and Han, D and Fang, X and Li, J and Zhu, Y and Zhao, Z and Kan, H and Ying, Z and Xu, Y}, title = {Gut microbiota mediates ambient PM2.5 exposure-induced abnormal glucose metabolism via short-chain fatty acids.}, journal = {Journal of hazardous materials}, volume = {476}, number = {}, pages = {135096}, pmid = {38996677}, issn = {1873-3336}, support = {R01 ES024516/ES/NIEHS NIH HHS/United States ; R01 ES032290/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Fatty Acids, Volatile/metabolism ; *Particulate Matter/toxicity ; Male ; *Insulin Resistance ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Glucose/metabolism ; Glucose Intolerance/metabolism ; Air Pollutants/toxicity ; Mice ; Anti-Bacterial Agents/pharmacology ; Dysbiosis/chemically induced/metabolism ; Feces/microbiology ; Sodium Acetate/pharmacology ; Glucose Tolerance Test ; Insulin/metabolism/blood ; }, abstract = {PM2.5 exposure has been found to cause gut dysbiosis and impair glucose homeostasis in human and animals, yet their underlying biological connection remain unclear. In the present study, we aim to investigate the biological significance of gut microbiota in PM2.5-induced glucose metabolic abnormalities. Our results showed that microbiota depletion by antibiotics treatment significantly alleviated PM2.5-induced glucose intolerance and insulin resistance, as indicated by the intraperitoneal glucose tolerance test, glucose-induced insulin secretion, insulin tolerance test, insulin-induced phosphorylation levels of Akt and GSK-3β in insulin sensitive tissues. In addition, faecal microbiota transplantation (FMT) from PM2.5-exposed donor mice successfully remodeled the glucose metabolism abnormalities in recipient mice, while the transplantation of autoclaved faecal materials did not. Faecal microbiota analysis demonstrated that the composition and alpha diversity of the gut bacterial community were altered by PM2.5 exposure and in FMT recipient mice. Furthermore, short-chain fatty acids levels analysis showed that the circulating acetate was significantly decreased in PM2.5-exposed donor and FMT recipient mice, and supplementation of sodium acetate for 3 months successfully improved the glucose metabolism abnormalities induced by PM2.5 exposure. These results indicate that manipulating gut microbiota or its metabolites could be a potential strategy for preventing the adverse health effects of ambient PM2.5.}, }
@article {pmid38996505, year = {2024}, author = {Jiang, ZM and Wang, FF and Zhao, YY and Lu, LF and Jiang, XY and Huang, TQ and Lin, Y and Guo, L and Weng, ZB and Liu, EH}, title = {Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1β pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {132}, number = {}, pages = {155847}, doi = {10.1016/j.phymed.2024.155847}, pmid = {38996505}, issn = {1618-095X}, mesh = {Animals ; *Hypericum/chemistry ; *Gastrointestinal Microbiome/drug effects ; *Depression/drug therapy ; *Tryptophan/metabolism/pharmacology ; Male ; *NF-kappa B/metabolism ; *Interleukin-1beta/metabolism ; Mice ; *Antidepressive Agents/pharmacology ; *Akkermansia ; Mice, Inbred C57BL ; Caspase 1/metabolism ; Fecal Microbiota Transplantation ; Verrucomicrobia ; Plant Extracts/pharmacology ; Signal Transduction/drug effects ; Dysbiosis/drug therapy/microbiology ; Disease Models, Animal ; }, abstract = {BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored.<br><br>PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL.<br><br>METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments.<br><br>RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NF&#x3ba;B-NLRP2-Caspase1-IL1&#x3b2; pathway and increased proinflammatory IL1&#x3b2; in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NF&#x3ba;B-NLRP2-Caspase1-IL1&#x3b2; pathway.<br><br>CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NF&#x3ba;B-NLRP2-Caspase1-IL1&#x3b2; pathway, specifically by targeting AKK and tryptophan metabolites.}, }
@article {pmid38993864, year = {2023}, author = {Dela Cruz, M and Lin, H and Han, J and Adler, E and Boissiere, J and Khalid, M and Sidebottom, A and Sundararajan, A and Lehmann, C and Moran, A and Odenwald, M and Stutz, M and Kim, G and Pinney, S and Jeevanandam, V and Alegre, ML and Pamer, E and Nguyen, AB}, title = {Reduced immunomodulatory metabolite concentrations in peri-transplant fecal samples from heart allograft recipients.}, journal = {Frontiers in transplantation}, volume = {2}, number = {}, pages = {1182534}, pmid = {38993864}, issn = {2813-2440}, abstract = {BACKGROUND: Emerging evidence is revealing the impact of the gut microbiome on hematopoietic and solid organ transplantation. Prior studies postulate that this influence is mediated by bioactive metabolites produced by gut-dwelling commensal bacteria. However, gut microbial metabolite production has not previously been measured among heart transplant (HT) recipients.<br><br>METHODS: In order to investigate the potential influence of the gut microbiome and its metabolites on HT, we analyzed the composition and metabolite production of the fecal microbiome among 48 HT recipients at the time of HT.<br><br>RESULTS: Compared to 20 healthy donors, HT recipients have significantly reduced alpha, i.e. within-sample, microbiota diversity, with significantly lower abundances of key anaerobic commensal bacteria and higher abundances of potentially pathogenic taxa that have been correlated with adverse outcomes in other forms of transplantation. HT recipients have a wide range of microbiota-derived fecal metabolite concentrations, with significantly reduced levels of immune modulatory metabolites such as short chain fatty acids and secondary bile acids compared to healthy donors. These differences were likely due to disease severity and prior antibiotic exposures but were not explained by other demographic or clinical factors.<br><br>CONCLUSIONS: Key potentially immune modulatory gut microbial metabolites are quantifiable and significantly reduced among HT recipients compared to healthy donors. Further study is needed to understand whether this wide range of gut microbial dysbiosis and metabolite alterations impact clinical outcomes and if they can be used as predictive biomarkers or manipulated to improve transplant outcomes.}, }
@article {pmid38993521, year = {2024}, author = {Ge, Y and Wang, J and Wu, L and Wu, J}, title = {Gut microbiota: a potential new regulator of hypertension.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1333005}, pmid = {38993521}, issn = {2297-055X}, abstract = {Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases and has become a global public health concern. Although hypertension results from a combination of factors, the specific mechanism is still unclear. However, increasing evidence suggests that gut microbiota is closely associated with the development of hypertension. We provide a summary of the composition and physiological role of gut microbiota. We then delve into the mechanism of gut microbiota and its metabolites involved in the occurrence and development of hypertension. Finally, we review various regimens for better-controlling hypertension from the diet, exercise, drugs, antibiotics, probiotics, and fecal transplantation perspectives.}, }
@article {pmid38992408, year = {2025}, author = {Ananthakrishnan, AN and Whelan, K and Allegretti, JR and Sokol, H}, title = {Diet and Microbiome-Directed Therapy 2.0 for IBD.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {23}, number = {3}, pages = {406-418}, doi = {10.1016/j.cgh.2024.05.049}, pmid = {38992408}, issn = {1542-7714}, mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Gastrointestinal Microbiome ; Probiotics/therapeutic use/administration &amp; dosage ; *Diet/methods ; Fecal Microbiota Transplantation/methods ; }, abstract = {Inflammatory bowel disease (IBD) comprises chronic and relapsing disorders of the gastrointestinal tract, characterized by dysregulated immune responses to the gut microbiome. The gut microbiome and diet are key environmental factors that influence the onset and progression of IBD and can be leveraged for treatment. In this review, we summarize the current evidence on the role of the gut microbiome and diet in IBD pathogenesis, and the potential of microbiome-directed therapies and dietary interventions to improve IBD outcomes. We discuss available data and the advantages and drawbacks of the different approaches to manipulate the gut microbiome, such as fecal microbiota transplantation, next-generation and conventional probiotics, and postbiotics. We also review the use of diet as a therapeutic tool in IBD, including the effects in induction and maintenance, special diets, and exclusive enteral nutrition. Finally, we highlight the challenges and opportunities for the translation of diet and microbiome interventions into clinical practice, such as the need for personalization, manufacturing and regulatory hurdles, and the specificity to take into account for clinical trial design.}, }
@article {pmid38992120, year = {2024}, author = {Ye, XX and Jiang, QY and Wu, MJ and Ye, QH and Zheng, H}, title = {Transplant of fecal microbiota from healthy young mice relieves cognitive defects in late-stage diabetic mice by reducing metabolic disorders and neuroinflammation.}, journal = {Acta pharmacologica Sinica}, volume = {45}, number = {12}, pages = {2513-2526}, pmid = {38992120}, issn = {1745-7254}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Diabetes Mellitus, Experimental/complications ; Mice ; Male ; *Neuroinflammatory Diseases ; *Gastrointestinal Microbiome ; *Mice, Inbred C57BL ; Cognitive Dysfunction/therapy ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Diabetes Mellitus, Type 1/complications ; Hippocampus/metabolism ; Metabolic Diseases/therapy/microbiology ; }, abstract = {Fecal microbiota transplant (FMT) is becoming as a promising area of interest for treating refractory diseases. In this study, we investigated the effects of FMT on diabetes-associated cognitive defects in mice as well as the underlying mechanisms. Fecal microbiota was prepared from 8-week-aged healthy mice. Late-stage type 1 diabetics (T1D) mice with a 30-week history of streptozotocin-induced diabetics were treated with antibiotics for 7 days, and then were transplanted with bacterial suspension (100 μL, i.g.) once a day for 14 days. We found that FMT from healthy young mice significantly alleviated cognitive defects of late-stage T1D mice assessed in Morris water maze test. We revealed that FMT significantly reduced the relative abundance of Gram-negative bacteria in the gut microbiota and enhanced intestinal barrier integrity, mitigating LPS translocation into the bloodstream and NLRP3 inflammasome activation in the hippocampus, thereby reducing T1D-induced neuronal loss and astrocytic proliferation. FMT also reshaped the metabolic phenotypes in the hippocampus of T1D mice especially for alanine, aspartate and glutamate metabolism. Moreover, we showed that application of aspartate (0.1 mM) significantly inhibited NLRP3 inflammasome activation and IL-1β production in BV2 cells under a HG/LPS condition. We conclude that FMT can effectively relieve T1D-associated cognitive decline via reducing the gut-brain metabolic disorders and neuroinflammation, providing a potential therapeutic approach for diabetes-related brain disorders in clinic.}, }
@article {pmid38990698, year = {2024}, author = {Wang, Z and Li, L and Li, W and Yan, H and Yuan, Y}, title = {Salidroside Alleviates Furan-Induced Impaired Gut Barrier and Inflammation via Gut Microbiota-SCFA-TLR4 Signaling.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {29}, pages = {16484-16495}, doi = {10.1021/acs.jafc.4c02433}, pmid = {38990698}, issn = {1520-5118}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Glucosides/pharmacology ; *Phenols/pharmacology ; *Toll-Like Receptor 4/metabolism/genetics ; Animals ; *Signal Transduction/drug effects ; *Furans/pharmacology ; Male ; *Fatty Acids, Volatile/metabolism ; Humans ; Mice ; *Bacteria/genetics/classification/isolation &amp; purification/metabolism/drug effects ; Intestinal Mucosa/metabolism/drug effects ; NF-kappa B/metabolism/genetics ; Rhodiola/chemistry ; Inflammation/metabolism/drug therapy ; Mice, Inbred C57BL ; }, abstract = {As a food contaminant that can be quickly absorbed through the gastrointestinal system, furan has been shown to disrupt the intestinal flora and barrier. Investigation of the intestinal toxicity mechanism of furan is of great significance to health. We previously identified the regulatory impact of salidroside (SAL) against furan-provoked intestinal damage, and the present work further explored whether the alleviating effect of SAL against furan-caused intestinal injury was based on the intestinal flora; three models, normal, pseudo-germ-free, and fecal microbiota transplantation (FMT), were established, and the changes in intestinal morphology, barrier, and inflammation were observed. Moreover, 16S rDNA sequencing observed the variation of the fecal flora associated with inflammation and short-chain fatty acids (SCFAs). Results obtained from the LC-MS/MS suggested that SAL increased furan-inhibited SCFA levels, activated the mRNA expressions of SCFA receptors (GPR41, GPR43, and GPR109A), and inhibited the furan-activated TLR4/MyD88/NF-κB signaling. Analysis of protein-protein interaction further confirmed the aforementioned effects of SAL, which inhibited furan-induced barrier damage and intestinal inflammation.}, }
@article {pmid38990027, year = {2024}, author = {Yang, Y and Zhang, Z and Wang, Y and Rao, J and Sun, J and Wu, Z and He, J and Tan, X and Liang, L and Yu, Q and Wu, Z and Zou, H and Zhang, H and Dong, M and Zheng, J and Feng, S and Cheng, W and Wei, H}, title = {Colonization of microbiota derived from Macaca fascicularis, Bama miniature pigs, beagle dogs, and C57BL/6J mice alleviates DSS-induced colitis in germ-free mice.}, journal = {Microbiology spectrum}, volume = {12}, number = {8}, pages = {e0038824}, pmid = {38990027}, issn = {2165-0497}, abstract = {Fecal microbiota transplantation (FMT) is an innovative and promising treatment for inflammatory bowel disease (IBD), which is related to the capability of FMT to supply functional microorganisms to improve recipient gut health. Numerous studies have highlighted considerable variability in the efficacy of FMT interventions for IBD. Several factors, including the composition of the donor microorganisms, significantly affect the efficacy of FMT in the treatment of IBD. Consequently, identifying the functional microorganisms in the donor is crucial for enhancing the efficacy of FMT. To explore potential common anti-inflammatory bacteria with therapeutic implications for IBD, germ-free (GF) BALB/c mice were pre-colonized with fecal microbiota obtained from diverse donors, including Macaca fascicularis (MCC_FMT), Bama miniature pigs (BP_FMT), beagle dogs (BD_FMT), and C57BL/6 J mice (Mice_FMT). Subsequently, mice were treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by MCC_FMT, BP_FMT, BD_FMT, and Mice_FMT, as demonstrated by the prevention of an elevated disease activity index in mice. Additionally, the utilization of distinct donors protected the intestinal barrier and contributed to the regulation of cytokine homeostasis. Metagenomic sequencing data showed that the microbial community structure and dominant species were significantly different among the four groups, which may be linked to variations in the anti-inflammatory efficacy observed in the respective groups. Notably, Lactobacillus reuteri and Flavonifractor plautii were consistently present in all four groups. L. reuteri exhibited a significant negative correlation with IL-1β, and animal studies further confirmed its efficacy in alleviating IBD, suggesting the presence of common functional bacteria across different donors that exert anti-inflammatory effects. This study provides essential foundational data for the potential clinical applications of FMT.IMPORTANCEDespite variations in efficacy observed among donors, numerous studies have underscored the potential of fecal microbiota transplantation (FMT) for managing inflammatory bowel disease (IBD), indicating the presence of shared anti-IBD bacterial species. In the present study, the collective anti-inflammatory efficacy observed across all four donor groups prompted the identification of two common bacterial species using metagenomics. A significant negative correlation between Lactobacillus reuteri and IL-1β was revealed. Furthermore, mice gavaged with L. reuteri successfully managed the colitis challenge induced by dextran sodium sulfate (DSS), suggesting that L. reuteri may act as an efficacious bacterium mediating shared anti-inflammatory effects among variable donors. This finding highlights the utilization of variable donors to screen FMT core bacteria, which may be a novel strategy for developing FMT applications.}, }
@article {pmid38989869, year = {2024}, author = {Gu, X and Yang, Z and Kou, Y and Yang, F and Wang, Y and Chen, Y and Wang, E and Jiang, X and Bai, Y and Zhang, Z and Zhang, S}, title = {Effects of Retrograde Colonic Enema-Based Fecal Microbiota Transplantation in the Treatment of Childhood Constipation: A Randomized, Double-Blind, Controlled Trial.}, journal = {The American journal of gastroenterology}, volume = {119}, number = {11}, pages = {2288-2297}, doi = {10.14309/ajg.0000000000002958}, pmid = {38989869}, issn = {1572-0241}, support = {30700917//National Natural Science Foundation of China/ ; 81570465//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Constipation/therapy/microbiology ; Double-Blind Method ; Female ; Male ; *Enema/methods ; *Fecal Microbiota Transplantation/methods ; Child ; Treatment Outcome ; Child, Preschool ; Adolescent ; Defecation ; }, abstract = {INTRODUCTION: Management of intractable childhood constipation is still challenging. The efficacy of retrograde colonic enema (RCE) with fecal microbiota transplantation (FMT) in intractable childhood constipation has not been established, although both have demonstrated potential in gastrointestinal diseases. The aim of this study was to determine the safety and efficacy of RCE-based FMT in the treatment of intractable constipation in children.<br><br>METHODS: A randomized, double-blind, controlled trial with 110 children was conducted. The patients were randomly assigned to the FMT with RCE group or the placebo with RCE group. All participants received a daily RCE, followed by a 4-week FMT treatment (twice a week) and a 12-week follow-up period. Spontaneous bowel movements &#x2265; 3 per week were the main outcomes, and the risk ratio with 95% confidence interval (CI) was calculated. Changes in intestinal bacterial profile were analyzed by BOX-PCR-based DNA fingerprinting and sequencing. The adverse effects were assessed based on symptoms.<br><br>RESULTS: At the end of the follow-up period, 22 patients (40.0%) in the FMT with RCE group and 10 patients (18.2%) in the placebo with RCE group had &#x2265; 3 spontaneous bowel movements per week (net difference = 21.8%, 95% CI: 13.2%-30.4%; risk ratio: 1.364, 95% CI: 1.063-1.749; P < 0.05). Both RCE and FMT enriched the intestinal bacterial diversity of patients with constipation. The adverse events were all mild self-limiting gastrointestinal symptoms.<br><br>DISCUSSION: FMT enhances the efficacy of RCE, and the use of RCE-based FMT is a safe and effective method in the treatment of intractable constipation in children.}, }
@article {pmid38989699, year = {2024}, author = {Boyle, BL and Khanna, S}, title = {Fecal microbiota live - jslm (Rebyota™/RBL) for management of recurrent Clostridioides difficile infection.}, journal = {Future microbiology}, volume = {19}, number = {14}, pages = {1243-1251}, pmid = {38989699}, issn = {1746-0921}, mesh = {Animals ; Humans ; Anti-Bacterial Agents/administration &amp; dosage/adverse effects ; *Clostridioides difficile ; *Clostridium Infections/therapy/microbiology ; Dysbiosis/chemically induced/microbiology/prevention &amp; control ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; Recurrence ; }, abstract = {There is an unmet need for effective treatments of Clostridioides difficile infection, an emerging health crisis in the United States. The management of C. difficile infection should include treatment of active infection and a strategy to prevent recurrence. Current gold standard therapy includes oral antibiotics which predispose patients to gut dysbiosis and increase the risk of recurrent infection. Addressing dysbiosis via fecal microbiota transplantation is an active and promising area of research, but studies have lacked standardization which makes outcome and safety data difficult to interpret. Rebyota™, formerly known as RBX2660, is a live biotherapeutic product designed using a standardized protocol and manufacturing process that has been shown to be effective for preventing recurrent C. difficile infection.}, }
@article {pmid38989143, year = {2024}, author = {Peng, Y and Huang, Y and Li, H and Li, C and Wu, Y and Chen, ZS and Wang, X and Liao, F and Miao, C}, title = {Huangqin Qingre Chubi Capsule inhibits rheumatoid arthritis by regulating intestinal flora and improving intestinal barrier.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1422245}, pmid = {38989143}, issn = {1663-9812}, abstract = {BACKGROUND: Changes in intestinal flora and intestinal barrier in patients with preclinical and diagnosed rheumatoid arthritis (RA) suggest that intestinal flora and intestinal barrier play an important role in the induction and persistence of RA. Huangqin Qingre Chubi Capsule (HQC) is a clinically effective herbal formula for the treatment of RA, but its therapeutic mechanism has not been fully clarified.<br><br>MATERIALS AND METHODS: In this study, real-time qPCR (RT-qPCR), 16SrRNA sequencing, Western blot (WB), immunofluorescence and other methods were used to investigate whether HQC inhibited RA.<br><br>RESULTS: Based on research in collages-induced arthritis (CIA) model in mice, human colon cancer cell line (Caco-2), and fibroblast-like synoviocytes (FLS) from RA patients, we found that intestinal flora was disturbed in CIA model group, intestinal barrier was damaged, and lipolyaccharide (LPS) level was increased, and HQC could regulate intestinal flora and intestinal barrier and reduce LPS translocation into blood. Antibiotic depletion weakened the anti-RA effect of HQC, and HQC fecal microbiota transplantation alleviated RA pathology. In addition, LPS increased the expression of RA pathologic factors MMP3, Fibronectin and inflammatory factors IL-6, TNF-&#x3b1;, IL-1&#x3b2; and IL-8, indicating that elevated peripheral blood level of LPS was related to RA pathology.<br><br>CONCLUSION: The dysregulation of intestinal flora and the disruption of intestinal barrier are significant factors in the development of RA. HQC improves RA by regulating intestinal flora, intestinal barrier and inhibiting LPS translocation into blood. The study unveiles RA's new pathogenesis and laid a scientific groundwork for advancing HQC therapy for RA.}, }
@article {pmid38988813, year = {2024}, author = {Sipos, D and Varga, A and Kappéter, &#xc1; and Halda-Kiss, B and Kása, P and Pál, S and Kocsis, B and Péterfi, Z}, title = {Encapsulation protocol for fecal microbiota transplantation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1424376}, pmid = {38988813}, issn = {2235-2988}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Clostridium Infections/therapy/microbiology ; *Feces/microbiology ; Treatment Outcome ; Female ; Clostridioides difficile ; Freeze Drying ; Male ; Middle Aged ; Aged ; Adult ; }, abstract = {INTRODUCTION: Clostridioides difficile infections (CDI) continue to pose a challenge for clinicians. Fecal microbiota transplantation (FMT) is an effective treatment option in CDI. Furthermore, recent and ongoing studies suggest potential benefits of FMT in other diseases as well.<br><br>METHODS: We would like to present a novel protocol for encapsulation of lyophilized fecal material. Our method provides with better compliance as well as improved flexibility, storage and safety.<br><br>RESULTS: FMT was conducted in 28 patients with an overall success rate of 82,14% using apsules containing lyophilized stool. 16 of patients were given capsules with lessened bacteria counts. The success rate in this group was 93,75%.<br><br>DISCUSSION: The results highlight the still unanswered questions about the mechanism of action and contribute to a wider use of FMT in the clinical praxis and in research.}, }
@article {pmid38988278, year = {2024}, author = {Yan, M and Man, S and Ma, L and Guo, L and Huang, L and Gao, W}, title = {Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.}, journal = {Clinical and molecular hepatology}, volume = {30}, number = {4}, pages = {620-648}, pmid = {38988278}, issn = {2287-285X}, support = {82074069//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Fatty Liver/complications/therapy/pathology ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adiposeliver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and fecal microbiota transplantation. Understanding the immunological mechanisms underlying SLD is crucial for advancing clinical therapeutic strategies.}, }
@article {pmid38987780, year = {2024}, author = {Long, AE and Pitta, D and Hennessy, M and Indugu, N and Vecchiarelli, B and Luethy, D and Aceto, H and Hurcombe, S}, title = {Assessment of fecal bacterial viability and diversity in fresh and frozen fecal microbiota transplant (FMT) product in horses.}, journal = {BMC veterinary research}, volume = {20}, number = {1}, pages = {306}, pmid = {38987780}, issn = {1746-6148}, support = {580-5805-1-461612-xxxx-2000-5872//Raymond Firestone Trust/ ; 580-5805-1-461612-xxxx-2000-5872//Raymond Firestone Trust/ ; }, mesh = {Animals ; Horses/microbiology ; *Feces/microbiology ; *Bacteria/classification/genetics/isolation &amp; purification ; *RNA, Ribosomal, 16S/genetics ; *Fecal Microbiota Transplantation/veterinary ; *Freezing ; Microbial Viability ; Cryopreservation/veterinary ; DNA, Bacterial/genetics ; }, abstract = {BACKGROUND: Currently, lack of standardization for fecal microbiota transplantation (FMT) in equine practice has resulted in highly variable techniques, and there is no data on the bacterial metabolic activity or viability of the administered product. The objectives of this study were to compare the total and potentially metabolically active bacterial populations in equine FMT, and assess the effect of different frozen storage times, buffers, and temperatures on an equine FMT product. Fresh feces collected from three healthy adult horses was subjected to different storage methods. This included different preservation solutions (saline plus glycerol or saline only), temperature (-20 °C or -80 °C), and time (fresh, 30, 60, or 90 days). Samples underwent DNA extraction to assess total bacterial populations (both live and dead combined) and RNA extraction followed by reverse transcription to cDNA as a proxy to assess viable bacteria, then 16s rRNA gene amplicon sequencing using the V1-V2 region.<br><br>RESULTS: The largest difference in population indices and taxonomic composition at the genus level was seen when evaluating the results of DNA-based (total) and cDNA-based (potentially metabolically active) extraction method. At the community level, alpha diversity (observed species, Shannon diversity) was significantly decreased in frozen samples for DNA-based analysis (P&#x2009;<&#x2009;0.05), with less difference seen for cDNA-based sequencing. Using DNA-based analysis, length of storage had a significant impact (P&#x2009;<&#x2009;0.05) on the bacterial community profiles. For potentially metabolically active populations, storage overall had less of an effect on the bacterial community composition, with a significant effect of buffer (P&#x2009;<&#x2009;0.05). Individual horse had the most significant effect within both DNA and cDNA bacterial communities.<br><br>CONCLUSIONS: Frozen storage of equine FMT material can preserve potentially metabolically active bacteria of the equine fecal microbiome, with saline plus glycerol preservation more effective than saline alone. Larger studies are needed to determine if these findings apply to other individual horses. The ability to freeze FMT material for use in equine patients could allow for easier clinical use of fecal transplant in horses with disturbances in their intestinal microbiome.}, }
@article {pmid38987677, year = {2024}, author = {van Rossen, TM and van Beurden, YH and Bogaards, JA and Budding, AE and Mulder, CJJ and Vandenbroucke-Grauls, CMJE}, title = {Fecal microbiota composition is a better predictor of recurrent Clostridioides difficile infection than clinical factors in a prospective, multicentre cohort study.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {687}, pmid = {38987677}, issn = {1471-2334}, support = {848016009//Netherlands Organization for Health Research and Development (ZonMw)/ ; 645.001.002//Dutch Organization for Scientific Research (NWO)/ ; }, mesh = {Humans ; *Clostridium Infections/microbiology/therapy ; Male ; Prospective Studies ; Female ; *Feces/microbiology ; Middle Aged ; Aged ; *Gastrointestinal Microbiome ; Clostridioides difficile/genetics ; Fecal Microbiota Transplantation ; Adult ; Recurrence ; Anti-Bacterial Agents/therapeutic use ; Aged, 80 and over ; Fidaxomicin/therapeutic use ; }, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhoea. Fidaxomicin and fecal microbiota transplantation (FMT) are effective, but expensive therapies to treat recurrent CDI (reCDI). Our objective was to develop a prediction model for reCDI based on the gut microbiota composition and clinical characteristics, to identify patients who could benefit from early treatment with fidaxomicin or FMT.<br><br>METHODS: Multicentre, prospective, observational study in adult patients diagnosed with a primary episode of CDI. Fecal samples and clinical data were collected prior to, and after 5 days of CDI treatment. Follow-up duration was 8 weeks. Microbiota composition was analysed by IS-pro, a bacterial profiling technique based on phylum- and species-specific differences in the 16-23&#xa0;S interspace regions of ribosomal DNA. Bayesian additive regression trees (BART) and adaptive group-regularized logistic ridge regression (AGRR) were used to construct prediction models for reCDI.<br><br>RESULTS: 209 patients were included, of which 25% developed reCDI. Variables related to microbiota composition provided better prediction of reCDI and were preferentially selected over clinical factors in joint prediction models. Bacteroidetes abundance and diversity after start of CDI treatment, and the increase in Proteobacteria diversity relative to baseline, were the most robust predictors of reCDI. The sensitivity and specificity of a BART model including these factors were 95% and 78%, but these dropped to 67% and 62% in out-of-sample prediction.<br><br>CONCLUSION: Early microbiota response to CDI treatment is a better predictor of reCDI than clinical prognostic factors, but not yet sufficient enough to predict reCDI in daily practice.}, }
@article {pmid38987594, year = {2024}, author = {Fujimoto, K and Hayashi, T and Yamamoto, M and Sato, N and Shimohigoshi, M and Miyaoka, D and Yokota, C and Watanabe, M and Hisaki, Y and Kamei, Y and Yokoyama, Y and Yabuno, T and Hirose, A and Nakamae, M and Nakamae, H and Uematsu, M and Sato, S and Yamaguchi, K and Furukawa, Y and Akeda, Y and Hino, M and Imoto, S and Uematsu, S}, title = {An enterococcal phage-derived enzyme suppresses graft-versus-host disease.}, journal = {Nature}, volume = {632}, number = {8023}, pages = {174-181}, pmid = {38987594}, issn = {1476-4687}, mesh = {Adult ; Aged ; Animals ; Female ; Humans ; Male ; Mice ; Middle Aged ; Young Adult ; *Bacteriophages/enzymology/genetics ; Biofilms/drug effects/growth &amp; development ; Dysbiosis/complications/microbiology ; *Enterococcus faecalis/drug effects/genetics/growth &amp; development/metabolism/virology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; *Graft vs Host Disease/complications/microbiology/prevention &amp; control/therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; In Vitro Techniques ; Intestines/drug effects/microbiology ; Perforin/metabolism ; Risk Factors ; Transplantation, Homologous/adverse effects ; Whole Genome Sequencing ; Drug Resistance, Bacterial/drug effects ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Changes in the gut microbiome have pivotal roles in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogenic haematopoietic cell transplantation (allo-HCT)[1-6]. However, effective methods for safely resolving gut dysbiosis have not yet been established. An expansion of the pathogen Enterococcus faecalis in the intestine, associated with dysbiosis, has been shown to be a risk factor for aGVHD[7-10]. Here we analyse the intestinal microbiome of patients with allo-HCT, and find that E. faecalis escapes elimination and proliferates in the intestine by forming biofilms, rather than by acquiring drug-resistance genes. We isolated cytolysin-positive highly pathogenic E. faecalis from faecal samples and identified an anti-E. faecalis enzyme derived from E. faecalis-specific bacteriophages by analysing bacterial whole-genome sequencing data. The antibacterial enzyme had lytic activity against the biofilm of E. faecalis in vitro and in vivo. Furthermore, in aGVHD-induced gnotobiotic mice that were colonized with E. faecalis or with patient faecal samples characterized by the domination of Enterococcus, levels of intestinal cytolysin-positive E. faecalis were decreased and survival was significantly increased in the group that was treated with the E. faecalis-specific enzyme, compared with controls. Thus, administration of a phage-derived antibacterial enzyme that is specific to biofilm-forming pathogenic E. faecalis-which is difficult to eliminate with existing antibiotics-might provide an approach to protect against aGVHD.}, }
@article {pmid38985782, year = {2024}, author = {Liow, YJ and Kamimura, I and Umezaki, M and Suda, W and Takayasu, L}, title = {Dietary fiber induces a fat preference associated with the gut microbiota.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0305849}, pmid = {38985782}, issn = {1932-6203}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dietary Fiber ; Male ; Mice ; *Mice, Inbred C57BL ; *Food Preferences ; *Diet, High-Fat/adverse effects ; Feces/microbiology ; Inulin/pharmacology/administration &amp; dosage ; Dietary Fats/pharmacology ; Feeding Behavior ; Bacteroides ; Clostridiales ; }, abstract = {Eating behavior is essential to human health. However, whether future eating behavior is subjected to the conditioning of preceding dietary composition is unknown. This study aimed to investigate the effect of dietary fiber consumption on subsequent nutrient-specific food preferences between palatable high-fat and high-sugar diets and explore its correlation with the gut microbiota. C57BL/6NJcl male mice were subjected to a 2-week dietary intervention and fed either a control (n = 6) or inulin (n = 6) diet. Afterward, all mice were subjected to a 3-day eating behavioral test to self-select from the simultaneously presented high-fat and high-sugar diets. The test diet feed intakes were recorded, and the mice's fecal samples were analyzed to evaluate the gut microbiota composition. The inulin-conditioned mice exhibited a preference for the high-fat diet over the high-sugar diet, associated with distinct gut microbiota composition profiles between the inulin-conditioned and control mice. The gut microbiota Oscillospiraceae sp., Bacteroides acidifaciens, and Clostridiales sp. positively correlated with a preference for fat. Further studies with fecal microbiota transplantation and eating behavior-related neurotransmitter analyses are warranted to establish the causal role of gut microbiota on host food preferences. Food preferences induced by dietary intervention are a novel observation, and the gut microbiome may be associated with this preference.}, }
@article {pmid38984661, year = {2024}, author = {Zhao, JT and Zhang, Y and Wang, XW and Zou, PY and Zhao, Z and Mei, H and Liu, YX and Su, NY and Zhu, YJ and Wang, B and Wei, YL and Chen, DF and Lan, CH}, title = {Long-term effects of fecal microbiota transplantation on gut microbiota after Helicobacter pylori eradication with bismuth quadruple therapy: A randomized controlled trial.}, journal = {Helicobacter}, volume = {29}, number = {4}, pages = {e13079}, doi = {10.1111/hel.13079}, pmid = {38984661}, issn = {1523-5378}, support = {82072253//National Natural Science Foundation of China/ ; 2022jstg020//Chongqing Appropriate Health Technology Promotion/ ; }, mesh = {Humans ; *Helicobacter Infections/therapy/microbiology/drug therapy ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Middle Aged ; *Helicobacter pylori/drug effects ; Adult ; *Anti-Bacterial Agents/therapeutic use ; Prospective Studies ; *Bismuth/therapeutic use ; Drug Therapy, Combination ; China ; Amoxicillin/therapeutic use ; Clarithromycin/therapeutic use ; Treatment Outcome ; Aged ; Feces/microbiology ; }, abstract = {BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known.<br><br>MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment.<br><br>RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group.<br><br>CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.}, }
@article {pmid38983955, year = {2024}, author = {Ma, BT and Sang, LX and Chang, B}, title = {Gastric microbiota transplantation as a potential treatment for immune checkpoint inhibitor-associated gastritis.}, journal = {World journal of gastroenterology}, volume = {30}, number = {24}, pages = {3123-3125}, pmid = {38983955}, issn = {2219-2840}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; Gastric Mucosa/microbiology/immunology/pathology/drug effects ; *Gastritis/microbiology/immunology/therapy/chemically induced ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/adverse effects ; Stomach/microbiology/immunology/surgery ; Treatment Outcome ; }, abstract = {Immune-related adverse events (irAEs) are complications of the use of immune checkpoint inhibitors (ICIs). ICI-associated gastritis is one of the main irAEs. The gastric microbiota is often related to the occurrence and development of many gastric diseases. Gastric microbiota adjustment may be used to treat gastric disorders in the future. Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis. Therefore, we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.}, }
@article {pmid38983862, year = {2024}, author = {Zhang, Q and Bi, Y and Zhang, B and Jiang, Q and Mou, CK and Lei, L and Deng, Y and Li, Y and Yu, J and Liu, W and Zhao, J}, title = {Current landscape of fecal microbiota transplantation in treating depression.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1416961}, pmid = {38983862}, issn = {1664-3224}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; *Depression/therapy/microbiology ; *Brain-Gut Axis ; *Dysbiosis/therapy ; Animals ; Treatment Outcome ; }, abstract = {Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecal microbiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the long-term safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies.}, }
@article {pmid38980456, year = {2024}, author = {Azuma, T and Sato, Y and Chiba, H and Haga, J}, title = {Appendiceal goblet cell adenocarcinoma newly classified by WHO 5th edition: a case report (a secondary publication).}, journal = {Surgical case reports}, volume = {10}, number = {1}, pages = {168}, pmid = {38980456}, issn = {2198-7793}, abstract = {BACKGROUND: Appendiceal goblet cell adenocarcinoma (AGCA) is a newly proposed cancer type in the 5th edition of the WHO Classification of Tumours in 2019. We experienced this rare form of appendiceal primary neoplasm.<br><br>CASE PRESENTATION: An 85-year-old male presented a positive fecal occult blood test. A series of imagings revealed a type 1 tumor, located on the appendiceal orifice. The subsequent biopsy made the diagnosis of signet-ring cell carcinoma. Consequently, he underwent the laparoscopic-assisted ileocecal resection. Initially, the tumor was suspected to be a Goblet cell carcinoid (GCC). There was a discrepancy between the histological and immunostaining findings: the tumor cells exhibited morphological similarities to GCCs, however displayed limited staining upon immunostaining. Ultimately, we concluded that the tumor should be classified as AGCA, by following WHO 5th Edition. AGCA represents a newly categorized subtype of adenocarcinomas. Because of our preoperative suspicion of malignancy, we performed tumor resection with regional lymph node dissection, despite the fact that most appendiceal malignant tumors are typically identified after an appendectomy.<br><br>CONCLUSION: We experienced a case that provides valuable insights into the comprehension of AGCA, a recently established pathological entity in the WHO 5th Edition. This article is an acceptable secondary publication of a case report that appeared in Azuma et al. (J Jpn Surg Assoc 83:1103-1108, 2022).}, }
@article {pmid38979196, year = {2024}, author = {Yang, Y and Chi, L and Hsiao, YC and Lu, K}, title = {Sex-specific effects of gut microbiome on shaping bile acid metabolism.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38979196}, issn = {2692-8205}, support = {P42 ES031007/ES/NIEHS NIH HHS/United States ; }, abstract = {Gut microbiome is a group of microorganisms that plays important roles in contributing to health and diseases. These bacterial compositions have been demonstrated to impact bile acids (BAs) profiles, either by directly metabolizing primary BAs to secondary BAs or indirect ways through host metabolism by influencing BAs synthesis, transportation and conjugation in liver. It has been observed sexually dimorphic gut microbiome and bile acids composition, with variations in expression levels of bile acid metabolizing genes in the liver. However, associations between sex-specific differences in gut microbiome and BAs profiles are not well understood. This study aimed to investigate whether gut microbiome could influence BAs profiles in host in a sexspecific manner. We transplanted cecum feces of male and female C57BL/6 mice to male mice and measured BAs concentrations in feces, serum and liver samples 7 days after fecal transplantation. We found different BAs profiles between mice with male and female gut microbiome, including altering levels and proportions of secondary BAs. We also observed varied expression levels of genes related to bile acid metabolism in the liver and distal ileum. Our results highlight sex-specific effects of gut microbiome on shaping bile acid metabolism through gut bacteria and regulation of host genes.}, }
@article {pmid38979127, year = {2024}, author = {He, H and Li, M and Qiu, Y and Wu, Z and Wu, L}, title = {Washed microbiota transplantation improves sleep quality in patients with sleep disorder by the gut-brain axis.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1415167}, pmid = {38979127}, issn = {1662-4548}, abstract = {BACKGROUND: The clinical impact of washed microbiota transplantation (WMT) from healthy donors in sleep disorder (SD) patients is unclear. This study aimed to investigate the effect of WMT in SD patients.<br><br>METHODS: The clinical data were collected from patients with different indications receiving 1-3 courses of WMT, divided into two groups by 7 points of PSQI scale. The score of PQSI and SF-36 scale was used to assess the improvement in sleep quality and life quality among patients with sleep disorders following WMT. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of patients with sleep disorders before and after WMT.<br><br>RESULTS: WMT significantly improved sleep quality in patients with sleep disorder in the short and medium term. WMT significantly improved sleep latency, sleep time and total score in the short term. WMT significantly improved sleep quality and total score in the medium term. In terms of sleep quality and sleep latency, the improvement value also increased with the increase of treatment course, and the improvement effect of multiple treatment course was better than that of single and double treatment course. In the total score, the improvement effect of double and multiple treatment was better than that of single treatment. WMT also improved quality of life in the sleep disorder group. WMT significantly improved general health, vitality, social function and mental health in the short term. WMT significantly improved role-physical, general health, vitality, and mental health in the medium term. WMT regulated the disturbed gut microbiota in patients with sleep disorders. In the normal sleep group, WMT had no effect on the decline of sleep quality in the short, medium and long term, and had an improving effect on the quality of life.<br><br>CONCLUSION: WMT could significantly improve sleep quality and life quality in patients with sleep disorders with no adverse events. The improvement in sleep quality resulting from WMT could lead to an overall enhancement in life quality. WMT could be a potentially effective treatment for patients with sleep disorders by regulating the gut microbiota.}, }
@article {pmid38978633, year = {2024}, author = {Watanangura, A and Meller, S and Farhat, N and Suchodolski, JS and Pilla, R and Khattab, MR and Lopes, BC and Bathen-Nöthen, A and Fischer, A and Busch-Hahn, K and Flieshardt, C and Gramer, M and Richter, F and Zamansky, A and Volk, HA}, title = {Behavioral comorbidities treatment by fecal microbiota transplantation in canine epilepsy: a pilot study of a novel therapeutic approach.}, journal = {Frontiers in veterinary science}, volume = {11}, number = {}, pages = {1385469}, pmid = {38978633}, issn = {2297-1769}, abstract = {INTRODUCTION: Anxiety and cognitive dysfunction are frequent, difficult to treat and burdensome comorbidities in human and canine epilepsy. Fecal microbiota transplantation (FMT) has been shown to modulate behavior in rodent models by altering the gastrointestinal microbiota (GIM). This study aims to investigate the beneficial effects of FMT on behavioral comorbidities in a canine translational model of epilepsy.<br><br>METHODS: Nine dogs with drug-resistant epilepsy (DRE) and behavioral comorbidities were recruited. The fecal donor had epilepsy with unremarkable behavior, which exhibited a complete response to phenobarbital, resulting in it being seizure-free long term. FMTs were performed three times, two weeks apart, and the dogs had follow-up visits at three and six months after FMTs. Comprehensive behavioral analysis, including formerly validated questionnaires and behavioral tests for attention deficit hyperactivity disorder (ADHD)- and fear- and anxiety-like behavior, as well as cognitive dysfunction, were conducted, followed by objective computational analysis. Blood samples were taken for the analysis of antiseizure drug (ASD) concentrations, hematology, and biochemistry. Urine neurotransmitter concentrations were measured. Fecal samples were subjected to analysis using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based Dysbiosis Index (DI) assessment, and short-chain fatty acid (SCFA) quantification.<br><br>RESULTS: Following FMT, the patients showed improvement in ADHD-like behavior, fear- and anxiety-like behavior, and quality of life. The excitatory neurotransmitters aspartate and glutamate were decreased, while the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and GABA/glutamate ratio were increased compared to baseline. Only minor taxonomic changes were observed, with a decrease in Firmicutes and a Blautia_A species, while a Ruminococcus species increased. Functional gene analysis, SCFA concentration, blood parameters, and ASD concentrations remained unchanged.<br><br>DISCUSSION: Behavioral comorbidities in canine IE could be alleviated by FMT. This study highlights FMT's potential as a novel approach to improving behavioral comorbidities and enhancing the quality of life in canine patients with epilepsy.}, }
@article {pmid38978509, year = {2024}, author = {Cantón, R and De Lucas Ramos, P and García-Botella, A and García-Lledó, A and Hernández-Sampelayo, T and Gómez-Pavón, J and González Del Castillo, J and Martín-Delgado, MC and Martín Sánchez, FJ and Martínez-Sellés, M and Molero García, JM and Moreno Guillén, S and Rodríguez-Artalejo, FJ and Reigadas, E and Del Campo, R and Serrano, S and Ruiz-Galiana, J and Bouza, E}, title = {Human intestinal microbiome: Role in health and disease.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {37}, number = {6}, pages = {438-453}, pmid = {38978509}, issn = {1988-9518}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {The study of the microbiota and the microbiome, and specifically the intestinal one, has determined great interest due to the possible association of their alterations with numerous diseases. These include entities as diverse as Crohn's disease, autism, diabetes, cancer or situations as prevalent today as obesity. In view of this situation, different recommendations have been performed regarding the use of probiotics, prebiotics, and postbiotics as modulators of the microbiota and the microbiome, seeking both preventive and therapeutic effects, and faecal material transfer (FMT) is proposed as an alternative. The latter has emerged as the only proven beneficial intervention on the intestinal microbiome, specifically in the treatment of recurrent colitis associated with Clostridioides difficile (R-CDI). In the rest of the entities, the lowering of laboratory costs has favored the study of the microbiome, which is resolved by delivering reports with catalogs of microorganisms, metabolites or supposed biomarkers without consensus on their composition associated with healthy or diseased microbiota and the disease. There is still insufficient evidence in any disease for interventions on the microbiome beyond FMT and R-CDI. Multi- and multi-disciplinary work with extensive research and the application of artificial intelligence in this field may shed light on the questions raised currently. Ethical issues must also be resolved in light of possible interventions within the umbrella of personalized medicine.}, }
@article {pmid38976982, year = {2024}, author = {Vehreschild, MJGT and Schreiber, S and von Müller, L and Epple, HJ and Manthey, C and Oh, J and Weinke, T and Wahler, S and Stallmach, A}, title = {[Need for improvement in the care of patients with Clostridioides difficile infections (CDI) - expert opinion in international comparison].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {62}, number = {7}, pages = {1032-1041}, doi = {10.1055/a-2293-7760}, pmid = {38976982}, issn = {1439-7803}, mesh = {Humans ; *Clostridium Infections/therapy/epidemiology ; Germany ; Quality Improvement ; Internationality ; Fecal Microbiota Transplantation ; Evidence-Based Medicine ; Needs Assessment ; Cross Infection/prevention &amp; control/epidemiology/therapy ; Practice Guidelines as Topic ; }, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI), as a nosocomial disease, is associated with high morbidity and mortality. Even though the incidence of CDI has been declining in Germany in recent years, the individual infection may pose a medical challenge despite therapeutic advances. The aim here is to clarify which gaps practitioners consider to be particularly serious in care and in the existing evidence base.<br><br>METHODS: In a moderated workshop of German CDI experts the topics considered as relevant were identified. A survey already conducted in five other countries (Australia, France, Great Britain, Canada, and Italy) was adapted and processed by 27 practitioners. During the evaluation, the topics perceived as particularly important were identified, the statements of the specialist groups were compared and changes in opinion were considered.<br><br>RESULTS: 27 fully completed questionnaires were evaluated. The need for improvement was primarily seen in the prevention of CDI recurrences (74.1%) and the treatment of recurrences (55.6%). Evidence deficits were noted in the treatment of recurrences (55.6%) and identification of risk factors for recurrences (48.1%). Improving care via fecal microbiota transfer (FMT) was named by 70.4%. For guidelines, more clarity (48.1%) and more regular updates (40.7%) were desired. For patients, better education on appropriate antibiotic use (52.0%) and choice of FMT were desired (48.1%).<br><br>SUMMARY: The German expert view and the international assessment is similar, when asked about the need for improvement in care and evidence gaps in the treatment of patients with CDI: The focus is on prevention and therapy of recurrent CDI. The problem of access to FMT is a German peculiarity that seems to need improvement.}, }
@article {pmid38976078, year = {2024}, author = {Fang, L and Ning, J}, title = {Gut virome and diabetes: discovering links, exploring therapies.}, journal = {Archives of microbiology}, volume = {206}, number = {8}, pages = {346}, pmid = {38976078}, issn = {1432-072X}, support = {NO.2022003//the Scientific Research Projects of Medical and Health Institutions of Longhua District, Shenzhen/ ; NO.2022003//the Scientific Research Projects of Medical and Health Institutions of Longhua District, Shenzhen/ ; No. HLPM201907020104//the High Level Project of Medicine in Longhua, ShenZhen/ ; No. HLPM201907020104//the High Level Project of Medicine in Longhua, ShenZhen/ ; NO.2024027//the Scientific Research Projects of Medical and Health Institutions of Longhua District, Shenzhen,/ ; NO.2024027//the Scientific Research Projects of Medical and Health Institutions of Longhua District, Shenzhen,/ ; }, mesh = {Humans ; *Virome ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 1/therapy/virology/immunology ; *Diabetes Mellitus, Type 2/therapy/virology ; *Fecal Microbiota Transplantation ; Animals ; Bacteriophages/genetics/physiology ; Viruses/genetics/classification ; }, abstract = {This review offers a comprehensive analysis of the intricate relationship between the gut virome and diabetes, elucidating the mechanisms by which the virome engages with both human cells and the intestinal bacteriome. By examining a decade of scientific literature, we provide a detailed account of the distinct viral variations observed in type 1 diabetes (T1D) and type 2 diabetes (T2D). Our synthesis reveals that the gut virome significantly influences the development of both diabetes types through its interactions, which indirectly modulate immune and inflammatory responses. In T1D, the focus is on eukaryotic viruses that stimulate the host's immune system, whereas T2D is characterized by a broader spectrum of altered phage diversities. Promisingly, in vitro and animal studies suggest fecal virome transplantation as a potential therapeutic strategy to alleviate symptoms of T2D and obesity. This study pioneers a holistic overview of the gut virome's role in T1D and T2D, its interplay with host immunity, and the innovative potential of fecal transplantation therapy in clinical diabetes management.}, }
@article {pmid38975247, year = {2024}, author = {Mehta, N and Goodenough, D and Gupta, NK and Thomas, S and Mehta, C and Prakash, R and Woodworth, MH and Kraft, CS and Fridkin, SK}, title = {Recurrent Clostridioides difficile Infection and Outcome of Fecal Microbiota Transplantation Use: A Population-Based Assessment.}, journal = {Open forum infectious diseases}, volume = {11}, number = {7}, pages = {ofae309}, pmid = {38975247}, issn = {2328-8957}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; U54CK000485/ACL/ACL HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; U54 CK000485/CK/NCEZID CDC HHS/United States ; TL1 TR002382/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection (rCDI). In the current study, we evaluated rates of rCDI and subsequent FMT in a large metropolitan area. We compared demographic and clinical differences in FMT recipients and nonrecipients and quantified differences in outcomes based on treatment modality.<br><br>METHODS: A retrospective community-wide cohort study was conducted using surveillance data from the Georgia Emerging Infections Program, the Georgia Discharge Data System, and locally maintained lists of FMTs completed across multiple institutions to evaluate all episodes of C. difficile infection (CDI) in this region between 2016 and 2019. Cases were limited to patients with rCDI and &#x2265;1 documented hospitalization. A propensity-matched cohort was created to compare rates of recurrence and mortality among matched patients based on FMT receipt.<br><br>RESULTS: A total of 3038 (22%) of 13 852 patients with CDI had rCDI during this period. In a propensity-matched cohort, patients who received an FMT had lower rates of rCDI (odds ratio, 0.6 [95% confidence interval, .38-.96) and a lower mortality rate (0.26 [.08-.82]). Of patients with rCDI, only 6% had received FMT. Recipients were more likely to be young, white, and female and less likely to have renal disease, diabetes, or liver disease, though these chronic illnesses were associated with higher rates of rCDI.<br><br>CONCLUSIONS: These data suggest FMT has been underused in a population-based assessment and that FMT substantially reduced risk of recurrence and death.}, }
@article {pmid38974034, year = {2024}, author = {Benvenuti, L and Di Salvo, C and Bellini, G and Seguella, L and Rettura, F and Esposito, G and Antonioli, L and Ceravolo, R and Bernardini, N and Pellegrini, C and Fornai, M}, title = {Gut-directed therapy in Parkinson's disease.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1407925}, pmid = {38974034}, issn = {1663-9812}, abstract = {Parkinson's disease (PD) is a common and slow-progressing neurodegenerative disorder characterized by motor and non-motor symptoms, including gastrointestinal (GI) dysfunctions. Over the last years, the microbiota-gut-brain (MGB) axis is emerging as a bacterial-neuro-immune ascending pathway that contributes to the progression of PD. Indeed, PD patients are characterized by changes in gut microbiota composition, alterations of intestinal epithelial barrier (IEB) and enteric neurogenic/inflammatory responses that, besides determining intestinal disturbances, contribute to brain pathology. In this context, despite the causal relationship between gut dysbiosis, impaired MGB axis and PD remains to be elucidated, emerging evidence shows that MGB axis modulation can represent a suitable therapeutical strategy for the treatment of PD. This review provides an overview of the available knowledge about the beneficial effects of gut-directed therapies, including dietary interventions, prebiotics, probiotics, synbiotics and fecal microbiota transplantation (FMT), in both PD patients and animal models. In this context, particular attention has been devoted to the mechanisms by which the modulation of MGB axis could halt or slow down PD pathology and, most importantly, how these approaches can be included in the clinical practice.}, }
@article {pmid38974001, year = {2024}, author = {Li, Y and Zhou, Z and Liang, X and Ding, J and He, Y and Sun, S and Cheng, W and Ni, Z and Yu, C}, title = {Gut Microbiota Disorder Contributes to the Production of IL-17A That Exerts Chemotaxis via Binding to IL-17RA in Endometriosis.}, journal = {Journal of inflammation research}, volume = {17}, number = {}, pages = {4199-4217}, pmid = {38974001}, issn = {1178-7031}, abstract = {INTRODUCTION: Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized.<br><br>METHODS: Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry.<br><br>RESULTS: High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects.<br><br>DISCUSSION: Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential.}, }
@article {pmid38973782, year = {2024}, author = {Kim, NH and Hamadani, M and Abedin, S}, title = {New investigational drugs for steroid-refractory acute graft-versus-host disease: a review of the literature.}, journal = {Expert opinion on investigational drugs}, volume = {33}, number = {8}, pages = {791-799}, pmid = {38973782}, issn = {1744-7658}, support = {R50 CA275856/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Graft vs Host Disease/drug therapy ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Drugs, Investigational/pharmacology/administration &amp; dosage ; Acute Disease ; Animals ; Drug Development ; Transplantation, Homologous ; Steroids/pharmacology/administration &amp; dosage ; }, abstract = {INTRODUCTION: Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a formidable obstacle in the field of allogeneic hematopoietic cell transplantation (allo-HCT), significantly contributing to patient morbidity and mortality. The current therapeutic landscape for SR-aGVHD is limited, often yielding suboptimal results, thereby emphasizing the urgent need for innovative and effective treatments.<br><br>AREAS COVERED: In light of the pivotal REACH2 trial, ruxolitinib phosphate, a Janus kinase inhibitor, has gained prominence as the standard treatment for SR-aGVHD. Nevertheless, a considerable number of patients either do not respond to or cannot tolerate this therapy. This review delves into emerging treatments for SR-aGVHD, including mesenchymal stromal cells (MSCs), fecal microbiota transplantation (FMT), CD3/CD7 blockade, neihulizumab, begelomab, tocilizumab, and vedolizumab. While some of these agents have shown encouraging results in early-phase trials, issues such as treatment-related toxicities and inconsistent responses in larger studies highlight the necessity for ongoing research.<br><br>EXPERT OPINION: Current trials exploring new agents and combination therapies offer hope for fulfilling the unmet clinical needs in SR-aGVHD, potentially leading to more effective and precise treatment strategies.}, }
@article {pmid38973540, year = {2024}, author = {Khalaf, R and Sciberras, M and Ellul, P}, title = {The role of the fecal microbiota in inflammatory bowel disease.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {36}, number = {11}, pages = {1249-1258}, doi = {10.1097/MEG.0000000000002818}, pmid = {38973540}, issn = {1473-5687}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/microbiology/therapy ; *Gastrointestinal Microbiome ; *Feces/microbiology ; *Probiotics/therapeutic use ; *Crohn Disease/microbiology/therapy ; Treatment Outcome ; Inflammatory Bowel Diseases/microbiology/therapy ; Dysbiosis ; }, abstract = {The understanding of the potential role of the microbiota in the pathogenesis of inflammatory bowel disease (IBD) is ever-evolving. Traditionally, the management of IBD has involved medical therapy and/or surgical intervention. IBD can be characterized by gut microbiome alterations through various pathological processes. Various studies delve into nontraditional methods such as probiotics and fecal microbiota transplant and their potential therapeutic effects. Fecal microbiota transplant involves the delivery of a balanced composition of gut microorganisms into an affected patient via multiple possible routes and methods, while probiotics consist of live microorganisms given via the oral route. At present, neither method is considered first-line treatment, however, fecal microbiota transplant has shown potential success in inducing and maintaining remission in ulcerative colitis. In a study by Kruis and colleagues, Escherichia coli Nissle 1917 was considered to be equivalent to mesalamine in mild ulcerative colitis. Alteration of the microbiome in the management of Crohn's disease is less well defined. Furthermore, variation in the clinical usefulness of 5-aminosalicylic acid medication has been attributed, in part, to its acetylation and inactivation by gut microbes. In summary, our understanding of the microbiome's role is continually advancing, with the possibility of paving the way for personalized medicine based on the microbiome.}, }
@article {pmid38973202, year = {2024}, author = {Sui, Y and Feng, X and Ma, Y and Zou, Y and Liu, Y and Huang, J and Zhu, X and Wang, J}, title = {BHBA attenuates endoplasmic reticulum stress-dependent neuroinflammation via the gut-brain axis in a mouse model of heat stress.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {30}, number = {7}, pages = {e14840}, pmid = {38973202}, issn = {1755-5949}, support = {2023YFD1801100//National Key Research and Development Program of China/ ; 32272967//National Natural Science Foundation of China/ ; 32273085//National Natural Science Foundation of China/ ; 2024GH-ZDXM-33//International Science and Technology Cooperation Program of China/ ; }, mesh = {Animals ; Mice ; *Endoplasmic Reticulum Stress/drug effects/physiology ; *Brain-Gut Axis/physiology/drug effects ; *Neuroinflammatory Diseases/metabolism/drug therapy ; *Gastrointestinal Microbiome/drug effects/physiology ; *Mice, Inbred C57BL ; Male ; *Disease Models, Animal ; *3-Hydroxybutyric Acid/pharmacology ; Heat Stress Disorders/metabolism ; Endoplasmic Reticulum Chaperone BiP ; Neuroprotective Agents/pharmacology ; Heat-Shock Response/physiology/drug effects ; }, abstract = {BACKGROUND: Heat stress (HS) commonly occurs as a severe pathological response when the body's sensible temperature exceeds its thermoregulatory capacity, leading to the development of chronic brain inflammation, known as neuroinflammation. Emerging evidence suggests that HS leads to the disruption of the gut microbiota, whereas abnormalities in the gut microbiota have been demonstrated to affect neuroinflammation. However, the mechanisms underlying the effects of HS on neuroinflammation are poorly studied. Meanwhile, effective interventions have been unclear. β-Hydroxybutyric acid (BHBA) has been found to have neuroprotective and anti-inflammatory properties in previous studies. This study aims to explore the modulatory effects of BHBA on neuroinflammation induced by HS and elucidate the underlying molecular mechanisms.<br><br>METHODS: An in&#xa0;vivo and in&#xa0;vitro model of HS was constructed under the precondition of BHBA pretreatment. The modulatory effects of BHBA on HS-induced neuroinflammation were explored and the underlying molecular mechanisms were elucidated by flow cytometry, WB, qPCR, immunofluorescence staining, DCFH-DA fluorescent probe assay, and 16S rRNA gene sequencing of colonic contents.<br><br>RESULTS: Heat stress was found to cause gut microbiota disruption in HS mouse models, and TM7 and [Previotella] spp. may be the best potential biomarkers for assessing the occurrence of HS. Fecal microbiota transplantation associated with BHBA effectively reversed the disruption of gut microbiota in HS mice. Moreover, BHBA may inhibit microglia hyperactivation, suppress neuroinflammation (TNF-&#x3b1;, IL-1&#x3b2;, and IL-6), and reduce the expression of cortical endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP) mainly through its modulatory effects on the gut microbiota (TM7, Lactobacillus spp., Ruminalococcus spp., and Prevotella spp.). In&#xa0;vitro experiments revealed that BHBA (1&#x2009;mM) raised the expression of the ERS marker GRP78, enhanced cellular activity, and increased the generation of reactive oxygen species (ROS) and anti-inflammatory cytokines (IL-10), while also inhibiting HS-induced apoptosis, ROS production, and excessive release of inflammatory cytokines (TNF-&#x3b1; and IL-1&#x3b2;) in mouse BV2 cells.<br><br>CONCLUSION: &#x3b2;-Hydroxybutyric acid may be an effective agent for preventing neuroinflammation in HS mice, possibly due to its ability to inhibit ERS and subsequent microglia neuroinflammation via the gut-brain axis. These findings lay the groundwork for future research and development of BHBA as a preventive drug for HS and provide fresh insights into techniques for treating neurological illnesses by modifying the gut microbiota.}, }
@article {pmid38971546, year = {2024}, author = {Tang, L and Zhang, X and Zhang, B and Chen, T and Du, Z and Song, W and Chen, W and Wang, C}, title = {Electroacupuncture remodels gut microbiota and metabolites in mice with perioperative neurocognitive impairment.}, journal = {Experimental gerontology}, volume = {194}, number = {}, pages = {112507}, doi = {10.1016/j.exger.2024.112507}, pmid = {38971546}, issn = {1873-6815}, mesh = {Animals ; *Electroacupuncture/methods ; *Gastrointestinal Microbiome/physiology ; Male ; Mice ; *Hippocampus/metabolism ; Mice, Inbred C57BL ; Brain-Gut Axis/physiology ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Neurocognitive Disorders/therapy/metabolism ; Neuroinflammatory Diseases/metabolism ; Memory ; Cognition ; }, abstract = {Gut microbiota and metabolites are considered key factors in the pathogenesis of perioperative neurocognitive disorders (PND), and the brain-gut axis may be a promising target for PND treatment. Electroacupuncture has been shown to improve a wide range of neurological disorders and to restore function to the gastrointestinal tract. Thus, we hypothesized whether electroacupuncture could remodel gut microbiota and neuroinflammation induced by anesthesia/surgery. First, we observed electroacupuncture at acupoints GV20, LI4 and PC6 significantly improved memory in behavioral tests. Next, we found electroacupuncture decreased the levels of inflammatory factors (NSE, S-100β, IL-6, etc.) in the hippocampus, indicating that nerve inflammation was blocked by electroacupuncture. Furthermore, via 16S rRNA sequence analysis and LC-MS analysis, the gut microbiota and its metabolites were appropriately restored after electroacupuncture treatment. Additionally, we further confirmed the restorative effect of electroacupuncture on PND by fecal transplantation. In conclusion, the role of electroacupuncture in improving cognitive function and protecting neurons may be related to the modulation of gut microbiota and their metabolite dysregulation, thereby inhibiting neuroinflammation in PND mice.}, }
@article {pmid38971010, year = {2024}, author = {Zeng, C and Wan, SR and Guo, M and Tan, XZ and Zeng, Y and Wu, Q and Xie, JJ and Yan, P and Long, Y and Zheng, L and Jiang, ZZ and Teng, FY and Xu, Y}, title = {Fecal virome transplantation: A promising strategy for the treatment of metabolic diseases.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {177}, number = {}, pages = {117065}, doi = {10.1016/j.biopha.2024.117065}, pmid = {38971010}, issn = {1950-6007}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Metabolic Diseases/therapy ; *Gastrointestinal Microbiome ; Animals ; *Virome ; Feces/virology/microbiology ; }, abstract = {Metabolic diseases are a group of disorders caused by metabolic abnormalities, including obesity, diabetes, non-alcoholic fatty liver disease, and more. Increasing research indicates that, beyond inherent metabolic irregularities, the onset and progression of metabolic diseases are closely linked to alterations in the gut microbiota, particularly gut bacteria. Additionally, fecal microbiota transplantation (FMT) has demonstrated effectiveness in clinically treating metabolic diseases, notably diabetes. Recent attention has also focused on the role of gut viruses in disease onset. This review first introduces the characteristics and influencing factors of gut viruses, then summarizes their potential mechanisms in disease development, highlighting their impact on gut bacteria and regulation of host immunity. We also compare FMT, fecal filtrate transplantation (FFT), washed microbiota transplantation (WMT), and fecal virome transplantation (FVT). Finally, we review the current understanding of gut viruses in metabolic diseases and the application of FVT in treating these conditions. In conclusion, FVT may provide a novel and promising treatment approach for metabolic diseases, warranting further validation through basic and clinical research.}, }
@article {pmid38970126, year = {2024}, author = {Zuppi, M and Vatanen, T and Wilson, BC and Golovina, E and Portlock, T and Cutfield, WS and Vickers, MH and O'Sullivan, JM}, title = {Fecal microbiota transplantation alters gut phage communities in a clinical trial for obesity.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {122}, pmid = {38970126}, issn = {2049-2618}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Bacteriophages/physiology/classification/isolation &amp; purification/genetics ; *Feces/microbiology/virology ; *Obesity/therapy/microbiology ; Double-Blind Method ; Female ; Adolescent ; Male ; Bacteria/classification/virology/genetics ; Metagenomics/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a therapeutic intervention used to treat diseases associated with the gut microbiome. In the human gut microbiome, phages have been implicated in influencing human health, with successful engraftment of donor phages correlated with FMT treatment efficacy. The impact that gastrointestinal phages exert on human health has primarily been connected to their ability to modulate the bacterial communities in the gut. Nonetheless, how FMT affects recipients' phage populations, and in turn, how this influences the gut environment, is not yet fully understood. In this study, we investigated the effects of FMT on the phageome composition of participants within the Gut Bugs Trial (GBT), a double-blind, randomized, placebo-controlled trial that investigated the efficacy of FMT in treating obesity and comorbidities in adolescents. Stool samples collected from donors at the time of treatment and recipients at four time points (i.e., baseline and 6 weeks, 12 weeks, and 26 weeks post-intervention), underwent shotgun metagenomic sequencing. Phage sequences were identified and characterized in silico to examine evidence of phage engraftment and to assess the extent of FMT-induced alterations in the recipients' phageome composition.<br><br>RESULTS: Donor phages engrafted stably in recipients following FMT, composing a significant proportion of their phageome for the entire course of the study (33.8&#x2009;&#xb1;&#x2009;1.2% in females and 33.9&#x2009;&#xb1;&#x2009;3.7% in males). Phage engraftment varied between donors and donor engraftment efficacy was positively correlated with their phageome alpha diversity. FMT caused a shift in recipients' phageome toward the donors' composition and increased phageome alpha diversity and variability over time.<br><br>CONCLUSIONS: FMT significantly altered recipients' phage and, overall, microbial populations. The increase in microbial diversity and variability is consistent with a shift in microbial population dynamics. This proposes that phages play a critical role in modulating the gut environment and suggests novel approaches to understanding the efficacy of FMT in altering the recipient's microbiome.<br><br>TRIAL REGISTRATION: The Gut Bugs Trial was registered with the Australian New Zealand Clinical Trials Registry (ACTR N12615001351505). Trial protocol: the trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.}, }
@article {pmid38970007, year = {2024}, author = {Wang, Y and Hu, Y and Shi, P}, title = {A meta-analysis of randomized controlled trials evaluating the effectiveness of fecal microbiota transplantation for patients with irritable bowel syndrome.}, journal = {BMC gastroenterology}, volume = {24}, number = {1}, pages = {217}, pmid = {38970007}, issn = {1471-230X}, mesh = {*Irritable Bowel Syndrome/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; Humans ; *Randomized Controlled Trials as Topic ; Treatment Outcome ; Gastrointestinal Microbiome ; Adult ; Emotions ; }, abstract = {OBJECTIVE: Multiple randomized controlled trials (RCTs) have investigated the efficacy of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), but have yielded inconsistent results. We updated the short-term and long-term efficacy of FMT in treating IBS, and performed a first-of-its-kind exploration of the relationship between gut microbiota and emotions.<br><br>METHODS: We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library using various search strategies to identify all eligible studies. The inclusion criteria for data extraction were randomized controlled trials (RCTs) that investigated the efficacy of fecal microbiota transplantation (FMT) compared to placebo in adult patients (&#x2265;&#x2009;18 years old) with irritable bowel syndrome (IBS). A meta-analysis was then performed to assess the summary relative risk (RR) and corresponding 95% confidence intervals (CIs).<br><br>RESULTS: Out of 3,065 potentially relevant records, a total of 10 randomized controlled trials (RCTs) involving 573 subjects met the eligibility criteria for inclusion in the meta-analysis. The meta-analyses revealed no significant differences in short-term (12 weeks) (RR 0.20, 95% CI -0.04 to 0.44), long-term (52 weeks) global improvement (RR 1.38, 95% CI 0.87 to 2.21), besides short-term (12 weeks) (SMD -&#x2009;48.16, 95% CI -102.13 to 5.81, I[2]&#x2009;=&#x2009;90%) and long-term (24 weeks) (SMD 2.16, 95% CI -60.52 to 64.83, I[2]&#x2009;=&#x2009;68%) IBS-SSS. There was statistically significant difference in short-term improvement of IBS-QoL (SMD 10.11, 95% CI 0.71 to 19.51, I[2]&#x2009;=&#x2009;82%), although there was a high risk of bias. In terms of long-term improvement (24 weeks and 54 weeks), there were no significant differences between the FMT and placebo groups (SMD 7.56, 95% CI 1.60 to 13.52, I[2]&#x2009;=&#x2009;0%; SMD 6.62, 95% CI -0.85 to 14.08, I[2]&#x2009;=&#x2009;0%). Sensitivity analysis indicated that there were visible significant effects observed when the criteria were based on Rome IV criteria (RR 16.48, 95% CI 7.22 to 37.62) and Gastroscopy (RR 3.25, 95%CI 2.37 to 4.47), Colonoscopy (RR 1.42, 95% CI 0.98 to 2.05). when using mixed stool FMT based on data from two RCTs, no significant difference was observed (RR 0.94, 95% CI 0.66 to -1.34). The remission of depression exhibited no significant difference between the FMT and placebo groups at the 12-week mark (SMD -&#x2009;0.26, 95% CI -3.09 to 2.58), and at 24 weeks (SMD -&#x2009;2.26, 95% CI -12.96 to 8.45). Furthermore, major adverse events associated with FMT were transient and self-limiting.<br><br>DISCUSSION: Based on the available randomized controlled trials (RCTs), the current evidence does not support the efficacy of FMT in improving global IBS symptoms in the long term. The differential results observed in subgroup analyses raise questions about the accurate identification of suitable populations for FMT. Further investigation is needed to better understand the reasons behind these inconsistent findings and to determine the true potential of FMT as a treatment for IBS.}, }
@article {pmid38969601, year = {2024}, author = {Yu, J and Chen, X and Yang, X and Zhang, B}, title = {Understanding gut dysbiosis for hepatocellular carcinoma diagnosis and treatment.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {35}, number = {11}, pages = {1006-1020}, doi = {10.1016/j.tem.2024.06.003}, pmid = {38969601}, issn = {1879-3061}, mesh = {Humans ; *Carcinoma, Hepatocellular/diagnosis ; *Dysbiosis ; *Liver Neoplasms/diagnosis ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiome can play a crucial role in hepatocellular carcinoma (HCC) progression through the enterohepatic circulation, primarily acting via metabolic reprogramming and alterations in the hepatic immune microenvironment triggered by microbe-associated molecular patterns (MAMPs), metabolites, and fungi. In addition, the gut microbiome shows potential as a biomarker for early HCC diagnosis and for assessing the efficacy of immunotherapy in unresectable HCC. This review examines how gut microbiota dysbiosis, with varied functional profiles, contributes to HCCs of different etiologies. We discuss therapeutic strategies to modulate the gut microbiome including diets, antibiotics, probiotics, fecal microbiota transplantation, and nano-delivery systems, and underscore their potential as an adjunctive treatment modality for HCC.}, }
@article {pmid38969161, year = {2024}, author = {Li, X and Shang, S and Wu, M and Song, Q and Chen, D}, title = {Gut microbial metabolites in lung cancer development and immunotherapy: Novel insights into gut-lung axis.}, journal = {Cancer letters}, volume = {598}, number = {}, pages = {217096}, doi = {10.1016/j.canlet.2024.217096}, pmid = {38969161}, issn = {1872-7980}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Lung Neoplasms/immunology/microbiology/metabolism/therapy ; *Immunotherapy/methods ; Tumor Microenvironment/immunology ; Fatty Acids, Volatile/metabolism ; Animals ; Tryptophan/metabolism ; Lung/microbiology/immunology/metabolism ; }, abstract = {Metabolic derivatives of numerous microorganisms inhabiting the human gut can participate in regulating physiological activities and immune status of the lungs through the gut-lung axis. The current well-established microbial metabolites include short-chain fatty acids (SCFAs), tryptophan and its derivatives, polyamines (PAs), secondary bile acids (SBAs), etc. As the study continues to deepen, the critical function of microbial metabolites in the occurrence and treatment of lung cancer has gradually been revealed. Microbial derivates can enter the circulation system to modulate the immune microenvironment of lung cancer. Mechanistically, oncometabolites damage host DNA and promote the occurrence of lung cancer, while tumor-suppresive metabolites directly affect the immune system to combat the malignant properties of cancer cells and even show considerable application potential in improving the efficacy of lung cancer immunotherapy. Considering the crosstalk along the gut-lung axis, in-depth exploration of microbial metabolites in patients' feces or serum will provide novel guidance for lung cancer diagnosis and treatment selection strategies. In addition, targeted therapeutics on microbial metabolites are expected to overcome the bottleneck of lung cancer immunotherapy and alleviate adverse reactions, including fecal microbiota transplantation, microecological preparations, metabolite synthesis and drugs targeting metabolic pathways. In summary, this review provides novel insights and explanations on the intricate interplay between gut microbial metabolites and lung cancer development, and immunotherapy through the lens of the gut-lung axis, which further confirms the possible translational potential of the microbiome metabolome in lung cancer treatment.}, }
@article {pmid38969094, year = {2024}, author = {Cheng, Z and Yang, L and Chu, H}, title = {The role of gut microbiota, exosomes, and their interaction in the pathogenesis of ALD.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.07.002}, pmid = {38969094}, issn = {2090-1224}, abstract = {BACKGROUND: The liver disorders caused by alcohol abuse are termed alcoholic-related liver disease (ALD), including alcoholic steatosis, alcoholic steatohepatitis, alcoholic hepatitis, and alcoholic cirrhosis, posing a significant threat to human health. Currently, ALD pathogenesis has not been completely clarified, which is likely to be related to the direct damage caused by alcohol and its metabolic products, oxidative stress, gut dysbiosis, and exosomes.<br><br>AIMS: The existing studies suggest that both the gut microbiota and exosomes contribute to the development of ALD. Moreover, there exists an interaction between the gut microbiota and exosomes. We discuss whether this interaction plays a role in the pathogenesis of ALD and whether it can be a potential therapeutic target for ALD treatment.<br><br>Chronic alcohol intake alters the diversity and composition of gut microbiota, which greatly contributes to ALD's progression. Some approaches targeting the gut microbiota, including probiotics, fecal microbiota transplantation, and phage therapy, have been confirmed to effectively ameliorate ALD in many animal experiments and/or several clinical trials. In ALD, the levels of exosomes and the expression profile of microRNA have also changed, which affects the pathogenesis of ALD. Moreover, there is an interplay between exosomes and the gut microbiota, which also putatively acts as a pathogenic factor of ALD.}, }
@article {pmid38969093, year = {2024}, author = {Bai, X and Duan, Z and Deng, J and Zhang, Z and Fu, R and Zhu, C and Fan, D}, title = {Ginsenoside Rh4 inhibits colorectal cancer via the modulation of gut microbiota-mediated bile acid metabolism.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.06.028}, pmid = {38969093}, issn = {2090-1224}, abstract = {INTRODUCTION: Dysbiosis of the gut microbiota is emerging as a pivotal factor in the pathogenesis of colorectal cancer (CRC). Ginsenoside Rh4 (Rh4) is an active compound isolated from ginseng with beneficial effects in modulating intestinal inflammation and gut microbiota dysbiosis, but how Rh4 regulates the gut microbiota to alleviate CRC remains underexplored.<br><br>OBJECTIVES: We investigated the impact of Rh4 on CRC and the mechanism of its action in inhibiting CRC via modulation of gut microbiota.<br><br>METHODS: We used the AOM/DSS model and employed transcriptomics, genomics and metabolomics techniques to explore the inhibitory impact of Rh4 on CRC. Furthermore, we employed experiments involving antibiotic treatment and fecal microbiota transplantation (FMT) to investigate the role of the gut microbiota. Finally, we elucidated the pivotal role of key functional bacteria and metabolites regulated by Rh4 in CRC.<br><br>RESULTS: Our research findings indicated that Rh4 repaired intestinal barrier damage caused by CRC, alleviated intestinal inflammation, and inhibited the development of CRC. Additionally, Rh4 inhibited CRC in a gut microbiota-dependent manner. Rh4 increased the diversity of gut microbiota, enriched the probiotic Akkermansia muciniphila (A. muciniphila), and alleviated gut microbiota dysbiosis caused by CRC. Subsequently, Rh4 regulated A. muciniphila-mediated bile acid metabolism. A. muciniphila promoted the production of UDCA by enhancing the activity of 7&#x3b1;-hydroxysteroid dehydrogenase (7&#x3b1;-HSDH). UDCA further activated FXR, modulated the TLR4-NF-&#x3ba;B signaling pathway, thus inhibiting the development of CRC.<br><br>CONCLUSION: Our results confirm that Rh4 inhibits CRC in a gut microbiota-dependent manner by modulating gut microbiota-mediated bile acid metabolism and promoting the production of UDCA, which further activates the FXR receptor and regulates the TLR4-NF-&#x3ba;B signaling pathway. Our results confirm that Rh4 has the potential to be used as a modulator of gut microbiota for preventing and treatment of CRC.}, }
@article {pmid38968058, year = {2024}, author = {Beckers, M and Coburn, B and Kalia, LV and Bloem, BR}, title = {A Randomized Controlled Trial of Fecal Microbiota Transplantation for Parkinson's Disease: Getting it right, if not PARFECT.}, journal = {Journal of Parkinson's disease}, volume = {14}, number = {5}, pages = {913-915}, pmid = {38968058}, issn = {1877-718X}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Parkinson Disease/therapy ; Randomized Controlled Trials as Topic ; }, }
@article {pmid38967596, year = {2024}, author = {Zhang, R and Yan, Z and Zhong, H and Luo, R and Liu, W and Xiong, S and Liu, Q and Liu, M}, title = {Gut microbial metabolites in MASLD: Implications of mitochondrial dysfunction in the pathogenesis and treatment.}, journal = {Hepatology communications}, volume = {8}, number = {7}, pages = {}, pmid = {38967596}, issn = {2471-254X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Mitochondria/metabolism ; Probiotics/therapeutic use ; Fatty Liver/metabolism/microbiology/therapy ; Prebiotics ; Anti-Bacterial Agents/therapeutic use ; Animals ; Oxidative Stress ; }, abstract = {With an increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global health problem. MASLD is well-known as a multifactorial disease. Mitochondrial dysfunction and alterations in the gut bacteria are 2 vital events in MASLD. Recent studies have highlighted the cross-talk between microbiota and mitochondria, and mitochondria are recognized as pivotal targets of the gut microbiota to modulate the host's physiological state. Mitochondrial dysfunction plays a vital role in MASLD and is associated with multiple pathological changes, including hepatocyte steatosis, oxidative stress, inflammation, and fibrosis. Metabolites are crucial mediators of the gut microbiota that influence extraintestinal organs. Additionally, regulation of the composition of gut bacteria may serve as a promising therapeutic strategy for MASLD. This study reviewed the potential roles of several common metabolites in MASLD, emphasizing their impact on mitochondrial function. Finally, we discuss the current treatments for MASLD, including probiotics, prebiotics, antibiotics, and fecal microbiota transplantation. These methods concentrate on restoring the gut microbiota to promote host health.}, }
@article {pmid38966558, year = {2024}, author = {Lin, L and Tang, R and Liu, Y and Li, Z and Li, H and Yang, H}, title = {Research on the anti-aging mechanisms of Panax ginseng extract in mice: a gut microbiome and metabolomics approach.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1415844}, pmid = {38966558}, issn = {1663-9812}, abstract = {Introduction: Aged-related brain damage and gut microbiome disruption are common. Research affirms that modulating the microbiota-gut-brain axis can help reduce age-related brain damage. Methods: Ginseng, esteemed in traditional Chinese medicine, is recognized for its anti-aging capabilities. However, previous Ginseng anti-aging studies have largely focused on diseased animal models. To this end, efforts were hereby made to explore the potential neuroprotective effects of fecal microbiota transplantation (FMT) from Ginseng-supplemented aged mice to those pre-treated with antibiotics. Results: As a result, FMT with specific modifications in natural aging mice improved animal weight gain, extended the telomere length, anti-oxidative stress in brain tissue, regulated the serum levels of cytokine, and balanced the proportion of Treg cells. Besides, FMT increased the abundance of beneficial bacteria of Lachnospiraceae, Dubosiella, Bacteroides, etc. and decreased the levels of potential pathogenic bacteria of Helicobacter and Lachnoclostridium in the fecal samples of natural aged mice. This revealed that FMT remarkably reshaped gut microbiome. Additionally, FMT-treated aged mice showed increased levels of metabolites of Ursolic acid, β-carotene, S-Adenosylmethionine, Spermidine, Guanosine, Celecoxib, Linoleic acid, etc., which were significantly positively correlated with critical beneficial bacteria above. Additionally, these identified critical microbiota and metabolites were mainly enriched in the pathways of Amino acid metabolism, Lipid metabolism, Nucleotide metabolism, etc. Furthermore, FMT downregulated p53/p21/Rb signaling and upregulated p16/p14, ATM/synapsin I/synaptophysin/PSD95, CREB/ERK/AKT signaling in brain damage following natural aging. Discussion: Overall, the study demonstrates that reprogramming of gut microbiota by FMT impedes brain damage in the natural aging process, possibly through the regulation of microbiota-gut-brain axis.}, }
@article {pmid38966047, year = {2024}, author = {Tominaga, K and Kojima, Y and Kawata, Y and Takahashi, K and Sato, H and Tsuchiya, A and Kamimura, K and Terai, S}, title = {An updated review on the treatment for diversion colitis and pouchitis, with a focus on the utility of autologous fecal microbiota transplantation and its relationship with the intestinal microbiota.}, journal = {Bioscience of microbiota, food and health}, volume = {43}, number = {3}, pages = {162-169}, pmid = {38966047}, issn = {2186-6953}, abstract = {Diversion colitis (DC) is characterized by mucosal inflammation in the defunctioned segment of the colon following a colostomy or ileostomy. The major causes of DC are an increase in the number of aerobic bacteria, a lack of short-chain fatty acids (SCFAs), and immune disorders in the diverted colon. However, its exact pathogenesis remains unknown. Various treatment strategies for DC have been explored, although none have been definitively established. Treatment approaches such as SCFAs, 5-aminosalicylic acid enemas, steroid enemas, and irrigation with fibers have been attempted, yielding various degrees of efficacies in mitigating mucosal inflammation. However, only individual case reports demonstrating the limited effect of the following therapies have been published: leukocytapheresis, dextrose (hypertonic glucose) spray, infliximab, an elemental diet, and coconut oil. The usefulness of probiotics for treating DC has recently been reported. Furthermore, fecal microbiota transplantation (FMT) has emerged as a promising treatment for DC. This review provides an update on the treatment strategies of DC, with a particular focus on FMT and its relationship with the intestinal microbiota. FMT may become the first choice of treatment for some patients in the future because of its low medical costs, ease of use, and minimal side effects. Furthermore, FMT can also be used for postoperative DC prophylaxis.}, }
@article {pmid38965449, year = {2024}, author = {Drew, L}, title = {Faecal transplants can treat some cancers - but probably won't ever be widely used.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {38965449}, issn = {1476-4687}, }
@article {pmid38964948, year = {2024}, author = {Zhu, Y and Self, WK and Holtzman, DM}, title = {An emerging role for the gut microbiome in tauopathy.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {6}, pages = {e00423}, pmid = {38964948}, issn = {1878-7479}, mesh = {Humans ; *Tauopathies/microbiology ; *Gastrointestinal Microbiome/physiology ; Animals ; Brain/metabolism/microbiology ; Brain-Gut Axis/physiology ; }, abstract = {Tauopathies constitute a group of neurodegenerative diseases characterized by abnormal aggregation of the protein tau, progressive neuronal and synaptic loss, and eventual cognitive and motor impairment. In this review, we will highlight the latest efforts investigating the intricate interplay between the gut microbiome and tauopathies. We discuss the physiological interactions between the microbiome and the brain as well as clinical and experimental evidence that suggests that the presence of tauopathy alters the composition of gut microbiota. We explore both animal and human studies that define causative relationships between the gut microbiome and tauopathy by directly manipulating or transferring gut microbiota. This review highlights future directions into identifying and mechanistically elucidating microbial species causally linked to tauopathies, with an ultimate goal of devising therapeutic targets towards the gut microbiome to treat tauopathies.}, }
@article {pmid38964511, year = {2024}, author = {Davido, B and Watson, AR and de Truchis, P and Galazzo, G and Dinh, A and Batista, R and Terveer, EM and Lawrence, C and Michelon, H and Jobard, M and Saleh-Mghir, A and Kuijper, EJ and Caballero, S}, title = {Bacterial diversity and specific taxa are associated with decolonization of carbapenemase-producing enterobacterales after fecal microbiota transplantation.}, journal = {The Journal of infection}, volume = {89}, number = {2}, pages = {106216}, doi = {10.1016/j.jinf.2024.106216}, pmid = {38964511}, issn = {1532-2742}, mesh = {Humans ; *Fecal Microbiota Transplantation ; Male ; Female ; Middle Aged ; Prospective Studies ; Adult ; *Gastrointestinal Microbiome ; *Feces/microbiology ; Aged ; Bacterial Proteins/genetics/metabolism ; Enterobacteriaceae Infections/therapy/microbiology ; beta-Lactamases/genetics ; Carrier State/microbiology/therapy ; Carbapenem-Resistant Enterobacteriaceae/genetics/isolation &amp; purification ; Biodiversity ; }, abstract = {OBJECTIVES: We evaluated the effect of fecal microbiota transplantation (FMT) on the clearance of carbapenemase-producing Enterobacterales (CPE) carriage.<br><br>METHODS: We performed a prospective, multi-center study, conducted among patients who received a single dose of FMT from one of four healthy donors. The primary endpoint was complete clearance of CPE carriage two weeks after FMT with a secondary endpoint at three months. Shotgun metagenomic sequencing was performed to assess gut microbiota composition of donors and recipients before and after FMT.<br><br>RESULTS: Twenty CPE-colonized patients were included in the study, where post-FMT 20% (n&#xa0;=&#xa0;4/20) of patients met the primary endpoint and 40% (n&#xa0;=&#xa0;8/20) of patients met the secondary endpoint. Kaplan-Meier curves between patients with FMT intervention and the control group (n&#xa0;=&#xa0;82) revealed a similar rate of decolonization between groups. Microbiota composition analyses revealed that response to FMT was not donor-dependent. Responders had a significantly lower relative abundance of CPE species pre-FMT than non-responders, and 14 days post-FMT responders had significantly higher bacterial species richness and alpha diversity compared to non-responders (p&#xa0;<&#xa0;0.05). Responder fecal samples were also enriched in specific species, with significantly higher relative abundances of Faecalibacterium prausnitzii, Parabacteroides distasonis, Collinsella aerofaciens, Alistipes finegoldii and Blautia_A sp900066335 (q<0.01) compared to non-responders.<br><br>CONCLUSION: FMT administration using the proposed regimen did not achieve statistical significance for complete CPE decolonization but was correlated with the relative abundance of specific bacterial taxa, including CPE species.}, }
@article {pmid38964253, year = {2024}, author = {Chen, S and Liu, H and Yan, C and Li, Y and Xiao, J and Zhao, X}, title = {Fecal microbiota transplantation provides insights into the consequences of transcriptome profiles and cell energy in response to circadian misalignment of chickens.}, journal = {Poultry science}, volume = {103}, number = {9}, pages = {103926}, pmid = {38964253}, issn = {1525-3171}, mesh = {Animals ; *Chickens ; *Fecal Microbiota Transplantation/veterinary ; *Transcriptome ; *Circadian Rhythm ; Poultry Diseases/microbiology ; Energy Metabolism ; Male ; }, abstract = {The circadian misalignment (CM) disordered circadian rhythms exert adverse effects on animals. Poultry as one of animals suffers health and welfare problems due to long-term lighting photoperiods caused by CM. However, the roles of CM on organ development, cell growth, metabolism and immune are still unclear in chickens. In this study, a Chinese dual-purpose native breed, was used to explore the effects of CM on transcriptomic pattern of brain and cell energy biogenesis, and further fecal microbiota transplantation (FMT) was applied to investigate its "therapy" effect from CM suffering. Our results showed that the CM led to stunting in brain and small intestine of chicken. CM decreased of cell proliferation, and energy production, mtDNA copies and expression of genes related to cell cycle or mitochondrial biogenetics, while it upregulated the reactive oxygen species (ROS) level and the sensitivity to inflammation. Interestingly, FMT rescued the organ developmental defects and cell dysfunctions induced by CM. Circadian misalignment brought about abnormal tissue and cell developments, energy biogenesis, and immune response in birds. This study provided a comprehensive perspective on understanding the regulation of CM and FMT on bird development and welfare.}, }
@article {pmid38963317, year = {2024}, author = {Xiong, Y and Pu, YN and Li, LY and Su, Y and Niu, JY and Xiao, ZY}, title = {Gut microbiota-derived metabolite trimethylamine N-oxide aggravates cognitive dysfunction induced by femoral fracture operation in mice.}, journal = {The Kaohsiung journal of medical sciences}, volume = {40}, number = {8}, pages = {732-743}, doi = {10.1002/kjm2.12873}, pmid = {38963317}, issn = {2410-8650}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Methylamines/metabolism/adverse effects ; Mice ; *Cognitive Dysfunction/metabolism/etiology ; Male ; *Femoral Fractures/metabolism/complications ; *Disease Models, Animal ; Microglia/metabolism ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Postoperative Cognitive Complications/metabolism/etiology ; Cytokines/metabolism ; Brain/metabolism ; }, abstract = {An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N-oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO-induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ-free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO-related POCD and improving the quality of life for elderly patients.}, }
@article {pmid38962126, year = {2024}, author = {Zou, S and Li, Y and Zou, Q and Yang, M and Li, H and Niu, R and Lai, H and Wang, J and Yang, X and Zhou, L}, title = {Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1403892}, pmid = {38962126}, issn = {1664-302X}, abstract = {INTRODUCTION: The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear.<br><br>METHODS: We aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models.<br><br>RESULTS: We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation.<br><br>CONCLUSION: In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.}, }
@article {pmid38961596, year = {2024}, author = {Mehra, P and Kumar, A}, title = {Emerging importance of stool preservation methods in OMICS studies with special focus on cancer biology.}, journal = {Cell biochemistry and function}, volume = {42}, number = {5}, pages = {e4063}, doi = {10.1002/cbf.4063}, pmid = {38961596}, issn = {1099-0844}, support = {//National Institute of Immunology/ ; }, mesh = {Humans ; *Feces/microbiology/chemistry ; *Gastrointestinal Microbiome ; *Neoplasms/metabolism ; Metabolomics ; Metagenomics ; }, abstract = {The intricate consortium of microorganisms in the human gut plays a crucial role in different physiological functions. The complex known-unknown elements of the gut microbiome are perplexing and the absence of standardized procedures for collecting and preserving samples has hindered continuous research in comprehending it. The technological bias produced because of lack of standard protocols has affected the reproducibility of results. The complex nature of diseases like colorectal cancer, gastric cancer, hepatocellular carcinoma and breast cancer require a thorough understanding of its etiology for an efficient and timely diagnosis. The designated protocols for collection and preservation of stool specimens have great variance, hence generate inconsistencies in OMICS studies. Due to the complications associated to the nature of sample, it is important to preserve the sample to be studied later in a laboratory or to be used in the future research purpose. Stool preservation is gaining importance due to the increased use of treatment options like fecal microbiota transplantation to cure conditions like recurrent Clostridium difficile infections and for OMICS studies including metagenomics, metabolomics and culturomics. This review provides an insight into the importance of omics studies for the identification and development of novel biomarkers for quick and noninvasive diagnosis of various diseases.}, }
@article {pmid38961326, year = {2024}, author = {Wang, B and Qiu, Y and Xie, M and Huang, P and Yu, Y and Sun, Q and Shangguan, W and Li, W and Zhu, Z and Xue, J and Feng, Z and Zhu, Y and Yang, Q and Wu, P}, title = {Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {237}, pmid = {38961326}, issn = {1471-2180}, support = {82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; }, mesh = {*Urinary Bladder Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome ; Animals ; Humans ; Mice ; *Immunotherapy/methods ; *Fecal Microbiota Transplantation ; *Bacteroidetes/genetics/immunology ; Female ; Male ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Middle Aged ; Aged ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVE: Bladder cancer(BCa) was a disease that seriously affects patients' quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer.<br><br>METHODS: We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms.<br><br>RESULTS: The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4[+]T and CD8[+]T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group.<br><br>CONCLUSION: P. distasonis delivery combined with &#x3b1;-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.}, }
@article {pmid38959670, year = {2024}, author = {Bum Lee, J and Huang, Y and Oya, Y and Nutzinger, J and LE Ang, Y and Sooi, K and Chul Cho, B and Soo, RA}, title = {Modulating the gut microbiome in non-small cell lung cancer: Challenges and opportunities.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {194}, number = {}, pages = {107862}, doi = {10.1016/j.lungcan.2024.107862}, pmid = {38959670}, issn = {1872-8332}, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/microbiology/therapy/immunology ; *Gastrointestinal Microbiome/immunology ; *Lung Neoplasms/microbiology/therapy/immunology ; Immunotherapy/methods ; Fecal Microbiota Transplantation/methods ; Animals ; }, abstract = {Despite the efficacy of immunotherapy in non-small cell lung cancer (NSCLC), the majority of the patients experience relapse with limited subsequent treatment options. Preclinical studies of various epithelial tumors, such as melanoma and NSCLC, have shown that harnessing the gut microbiome resulted in improvement of therapeutic responses to immunotherapy. Is this review, we summarize the role of microbiome, including lung and gut microbiome in the context of NSCLC, provide overview of the mechanisms of microbiome in efficacy and toxicity of chemotherapies and immunotherapies, and address current ongoing clinical trials for NSCLC including fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs).}, }
@article {pmid38959643, year = {2024}, author = {Cheng, X and Hu, Y and Kuang, J and Guo, X and Cao, H and Wu, H and Hu, G and Zhuang, Y}, title = {Berberine alleviates high-energy and low-protein diet-induced fatty liver hemorrhagic syndrome in laying hens: insights from microbiome and metabolomics.}, journal = {Poultry science}, volume = {103}, number = {8}, pages = {103968}, pmid = {38959643}, issn = {1525-3171}, mesh = {Animals ; *Chickens ; *Gastrointestinal Microbiome/drug effects ; Female ; *Poultry Diseases/microbiology/prevention &amp; control ; *Animal Feed/analysis ; *Berberine/pharmacology/administration &amp; dosage ; Diet, Protein-Restricted/veterinary ; Metabolomics ; Fatty Liver/veterinary ; Lipid Metabolism/drug effects ; Dietary Supplements/analysis ; }, abstract = {Berberine (BBR), a well-known quaternary ammonium alkaloid, is recognized for its ability to prevent and alleviate metabolic disorders because of its anti-oxidative and anti-inflammatory properties. However, the underlying mechanisms of BBR to mitigate fatty liver hemorrhagic syndrome (FLHS) through the modulation of gut microbiota and their metabolism remained unclear. The results revealed that BBR ameliorates lipid metabolism disorder in high-energy and low-protein (HELP) diet-induced FLHS laying hens, as evidenced by improved liver function and lipid deposition of the liver, reduced blood lipids, and the expression of liver lipid synthesis-related factors. Moreover, BBR alleviated HELP diet-induced barrier dysfunction, increased microbial population, and dysregulated lipid metabolism in the ileum. BBR reshaped the HELP-perturbed gut microbiota, particularly declining the abundance of Desulfovibrio_piger and elevating the abundance of Bacteroides_salanitronis_DSM_18170. Meanwhile, metabolomic profiling analysis revealed that BBR reshaped microbial metabolism and function, particularly by reducing the levels of hydrocinnamic acid, dehydroanonaine, and leucinic acid. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that BBR-enriched gut microbiota alleviated hepatic lipid deposition and intestinal inflammation compared with those chicks that received a gut microbiota by HELP. Collectively, our study provided evidence that BBR effectively alleviated FLHS induced by HELP by reshaping the microbial and metabolic homeostasis within the liver-gut axis.}, }
@article {pmid38956725, year = {2024}, author = {Chen, J and Zhang, C and Yang, Z and Wu, W and Zou, W and Xin, Z and Zheng, S and Liu, R and Yang, L and Peng, H}, title = {Intestinal microbiota imbalance resulted by anti-Toxoplasma gondii immune responses aggravate gut and brain injury.}, journal = {Parasites &amp; vectors}, volume = {17}, number = {1}, pages = {284}, pmid = {38956725}, issn = {1756-3305}, support = {82330072//Key project of National Natural Science Foundation of China/ ; 82272364//National Natural Science Foundation of China/ ; 2023A1515011733//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Toxoplasma/immunology ; *Mice, Knockout ; *Brain Injuries/immunology ; Probiotics/administration &amp; dosage ; Brain/immunology ; Lactobacillus ; Disease Models, Animal ; Immunocompromised Host ; Toxoplasmosis/immunology ; RNA, Ribosomal, 16S/genetics ; Male ; Intestines/immunology ; }, abstract = {BACKGROUND: Toxoplasma gondii infection affects a significant portion of the global population, leading to severe toxoplasmosis and, in immunocompromised patients, even death. During T. gondii infection, disruption of gut microbiota further exacerbates the damage to intestinal and brain barriers. Therefore, identifying imbalanced probiotics during infection and restoring their equilibrium can regulate the balance of gut microbiota metabolites, thereby alleviating tissue damage.<br><br>METHODS: Vimentin gene knockout (vim-/-) mice were employed as an immunocompromised model to evaluate the influence of host immune responses on gut microbiota balance during T. gondii infection. Behavioral experiments were performed to assess changes in cognitive levels and depressive tendencies between chronically infected vim-/- and wild-type (WT) mice. Fecal samples were subjected to 16S ribosomal RNA (rRNA) sequencing, and serum metabolites were analyzed to identify potential gut probiotics and their metabolites for the treatment of T. gondii infection.<br><br>RESULTS: Compared to the immunocompetent WT sv129&#xa0;mice, the immunocompromised mice exhibited lower levels of neuronal apoptosis and fewer neurobehavioral abnormalities during chronic infection. 16S rRNA sequencing revealed a significant decrease in the abundance of probiotics, including several species of Lactobacillus, in WT mice. Restoring this balance through the administration of Lactobacillus murinus and Lactobacillus gasseri significantly suppressed the T. gondii burden in the intestine, liver, and brain. Moreover, transplantation of these two Lactobacillus spp. significantly improved intestinal barrier damage and alleviated inflammation and neuronal apoptosis in the central nervous system. Metabolite detection studies revealed that the levels of various Lactobacillus-related metabolites, including indole-3-lactic acid (ILA) in serum, decreased significantly after T. gondii infection. We confirmed that L. gasseri secreted much more ILA than L. murinus. Notably, ILA can activate the aromatic hydrocarbon receptor signaling pathway in intestinal epithelial cells, promoting the activation of CD8[+] T cells and the secretion of interferon-gamma.<br><br>CONCLUSION: Our study revealed that host immune responses against T. gondii infection severely disrupted the balance of gut microbiota, resulting in intestinal and brain damage. Lactobacillus spp. play a crucial role in immune regulation, and the metabolite ILA is a promising therapeutic compound for efficient and safe treatment of T. gondii infection.}, }
@article {pmid38955400, year = {2024}, author = {Swarte, JC and Zhang, S and Nieuwenhuis, LM and Gacesa, R and Knobbe, TJ and ,  and De Meijer, VE and Damman, K and Verschuuren, EAM and Gan, TC and Fu, J and Zhernakova, A and Harmsen, HJM and Blokzijl, H and Bakker, SJL and Björk, JR and Weersma, RK and , }, title = {Multiple indicators of gut dysbiosis predict all-cause and cause-specific mortality in solid organ transplant recipients.}, journal = {Gut}, volume = {73}, number = {10}, pages = {1650-1661}, doi = {10.1136/gutjnl-2023-331441}, pmid = {38955400}, issn = {1468-3288}, mesh = {Humans ; *Dysbiosis/mortality ; *Gastrointestinal Microbiome ; Female ; Male ; Middle Aged ; *Organ Transplantation/adverse effects ; Prospective Studies ; Cause of Death ; Transplant Recipients/statistics &amp; numerical data ; Adult ; Feces/microbiology ; Netherlands/epidemiology ; Metagenome ; Aged ; }, abstract = {OBJECTIVE: Gut microbiome composition is associated with multiple diseases, but relatively little is known about its relationship with long-term outcome measures. While gut dysbiosis has been linked to mortality risk in the general population, the relationship with overall survival in specific diseases has not been extensively studied. In the current study, we present results from an in-depth analysis of the relationship between gut dysbiosis and all-cause and cause-specific mortality in the setting of solid organ transplant recipients (SOTR).<br><br>DESIGN: We analysed 1337 metagenomes derived from faecal samples of 766 kidney, 334 liver, 170 lung and 67 heart transplant recipients part of the TransplantLines Biobank and Cohort-a prospective cohort study including extensive phenotype data with 6.5 years of follow-up. To analyze gut dysbiosis, we included an additional 8208 metagenomes from the general population of the same geographical area (northern Netherlands). Multivariable Cox regression and a machine learning algorithm were used to analyse the association between multiple indicators of gut dysbiosis, including individual species abundances, and all-cause and cause-specific mortality.<br><br>RESULTS: We identified two patterns representing overall microbiome community variation that were associated with both all-cause and cause-specific mortality. The gut microbiome distance between each transplantation recipient to the average of the general population was associated with all-cause mortality and death from infection, malignancy and cardiovascular disease. A multivariable Cox regression on individual species abundances identified 23 bacterial species that were associated with all-cause mortality, and by applying a machine learning algorithm, we identified a balance (a type of log-ratio) consisting of 19 out of the 23 species that were associated with all-cause mortality.<br><br>CONCLUSION: Gut dysbiosis is consistently associated with mortality in SOTR. Our results support the observations that gut dysbiosis is associated with long-term survival. Since our data do not allow us to infer causality, more preclinical research is needed to understand mechanisms before we can determine whether gut microbiome-directed therapies may be designed to improve long-term outcomes.}, }
@article {pmid38951925, year = {2024}, author = {Rasmussen, TS and Mao, X and Forster, S and Larsen, SB and Von Münchow, A and Tranæs, KD and Brunse, A and Larsen, F and Mejia, JLC and Adamberg, S and Hansen, AK and Adamberg, K and Hansen, CHF and Nielsen, DS}, title = {Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {119}, pmid = {38951925}, issn = {2049-2618}, support = {R324-2019-1880//The Lundbeck Foundation/ ; NNF-20OC0063874//Novo Nordisk Fonden/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Animals ; Mice ; *Bacteriophages/physiology/isolation &amp; purification ; *Clostridium Infections/therapy/microbiology ; *Gastrointestinal Microbiome ; *Feces/microbiology/virology ; *Clostridioides difficile ; Disease Models, Animal ; Humans ; Mice, Inbred C57BL ; Female ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinder their wider clinical application in treating less acute diseases.<br><br>METHODS: To overcome these challenges, we developed methods to broaden FVT's clinical application while maintaining efficacy and increasing safety. Specifically, we employed the following approaches: (1) chemostat-fermentation to reproduce the bacteriophage FVT donor component and remove eukaryotic viruses (FVT-ChP), (2) solvent-detergent treatment to inactivate enveloped viruses (FVT-SDT), and (3) pyronin-Y treatment to inhibit RNA virus replication (FVT-PyT). We assessed the efficacy of these processed FVTs in a C. difficile infection mouse model and compared them with untreated FVT (FVT-UnT), FMT, and saline.<br><br>RESULTS: FVT-SDT, FVT-UnT, and FVT-ChP reduced the incidence of mice reaching the humane endpoint (0/8, 2/7, and 3/8, respectively) compared to FMT, FVT-PyT, and saline (5/8, 7/8, and 5/7, respectively) and significantly reduced the load of colonizing C. difficile cells and associated toxin A/B levels. There was a potential elimination of C. difficile colonization, with seven out of eight mice treated with FVT-SDT testing negative with qPCR. In contrast, all other treatments exhibited the continued presence of C. difficile. Moreover, the results were supported by changes in the gut microbiome profiles, cecal cytokine levels, and histopathological findings. Assessment of viral engraftment following FMT/FVT treatment and host-phage correlations analysis suggested that transfer of phages likely were an important contributing factor associated with treatment efficacy.<br><br>CONCLUSIONS: This proof-of-concept study shows that specific modifications of FVT hold promise in addressing challenges related to donor variability and infection risks. Two strategies lead to treatments significantly limiting C. difficile colonization in mice, with solvent/detergent treatment and chemostat propagation of donor phages emerging as promising approaches. Video Abstract.}, }
@article {pmid38948828, year = {2024}, author = {Ngo, VL and Wang, Y and Shi, Z and Ramani, S and Jiang, B and T Gewirtz, A}, title = {Gut-resident C. perfringens impedes rotavirus vaccine efficacy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.06.17.599343}, pmid = {38948828}, issn = {2692-8205}, abstract = {BACKGROUND &amp; AIMS: The extent to which live orally-administered rotavirus (RV) vaccines elicit protective immunity is highly heterogeneous. We hypothesized microbiota composition might influence vaccine efficacy.<br><br>METHODS: We tested this concept by examining extent to which colonizing mice with segmented filamentous bacteria (SFB) influenced RV vaccine efficacy.Influence of human microbiomes on RV vaccination was studied via administering germ-free mice fecal microbial transplants (FMT) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to vaccination and challenge doses of RV.<br><br>RESULTS: SFB administration resulted in a phenotype reminiscent of RV vaccine failure, i.e. minimal generation of RV antigens and, consequently, lack of anti-RV antibodies resulting in proneness to RV challenge once SFB levels diminished. Transplant of microbiomes from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMT from high-responding children exhibited high levels of fecal RV antigen shedding and RV antibodies in response to RV vaccination and, concomitantly, were impervious to RV challenge. In contrast, mice receiving FMT from children who had not responded to RV vaccination exhibited only modest responses to RV challenge and, accordingly, remained prone to RV challenge. Microbiome analysis ruled out a role for SFB but suggested that RV vaccine failure might involve Clostridium perfringens . Oral administration of cultured C. perfringens to gnotobiotic mice partially recapitulated the RV vaccine non-responder phenotype. Analysis of previously-reported microbiome data found C. perfringens abundance in children associated with RV vaccine failure.<br><br>CONCLUSION: Microbiota composition influences RV vaccine virus infection and, consequently, protective immunity. C. perfringens may be one, perhaps of many, bacterial species harbored in the intestine of RV-vaccine non-responders that influences RV vaccine outcomes.}, }
@article {pmid38948060, year = {2024}, author = {Yan, J and Zhang, X and Zhu, K and Yu, M and Liu, Q and De Felici, M and Zhang, T and Wang, J and Shen, W}, title = {Sleep deprivation causes gut dysbiosis impacting on systemic metabolomics leading to premature ovarian insufficiency in adolescent mice.}, journal = {Theranostics}, volume = {14}, number = {9}, pages = {3760-3776}, pmid = {38948060}, issn = {1838-7640}, mesh = {Animals ; Female ; *Primary Ovarian Insufficiency/metabolism ; *Gastrointestinal Microbiome ; Mice ; *Dysbiosis/microbiology/metabolism ; *Metabolomics/methods ; *Sleep Deprivation/complications/metabolism ; Ovarian Follicle/metabolism ; Oocytes/metabolism ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Apoptosis ; }, abstract = {Rationale: Currently, there are occasional reports of health problems caused by sleep deprivation (SD). However, to date, there remains a lack of in-depth research regarding the effects of SD on the growth and development of oocytes in females. The present work aimed to investigate whether SD influences ovarian folliculogenesis in adolescent female mice. Methods: Using a dedicated device, SD conditions were established in 3-week old female mice (a critical stage of follicular development) for 6 weeks and gut microbiota and systemic metabolomics were analyzed. Analyses were related to parameters of folliculogenesis and reproductive performance of SD females. Results: We found that the gut microbiota and systemic metabolomics were severely altered in SD females and that these were associated with parameters of premature ovarian insufficiency (POI). These included increased granulosa cell apoptosis, reduced numbers of primordial follicles (PmFs), correlation with decreased AMH, E2, and increased LH in blood serum, and a parallel increased number of growing follicles and changes in protein expression compatible with PmF activation. SD also reduced oocyte maturation and reproductive performance. Notably, fecal microbial transplantation from SD females into normal females induced POI parameters in the latter while niacinamide (NAM) supplementation alleviated such symptoms in SD females. Conclusion: Gut microbiota and alterations in systemic metabolomics caused by SD induced POI features in juvenile females that could be counteracted with NAM supplementation.}, }
@article {pmid38942038, year = {2024}, author = {Dhanda, AD and Allgar, V and Bhala, N and Callaghan, L and Castro, J and Chokshi, S and Clements, A and Drummond, C and Forrest, EH and Manning, L and Parker, R and Shawcross, DL and Towey, J}, title = {Breaking down barriers between liver, addiction, and mental health services for people with alcohol-related liver disease.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {9}, number = {10}, pages = {903-905}, doi = {10.1016/S2468-1253(24)00189-4}, pmid = {38942038}, issn = {2468-1253}, mesh = {Humans ; *Mental Health Services ; *Liver Diseases, Alcoholic/therapy ; Health Services Accessibility ; Alcoholism/psychology ; }, }
@article {pmid38941942, year = {2024}, author = {Teng, M and Sun, J and Zhao, L and Li, Y and Zhang, Z and Zhu, W and Zhang, Y and Xu, F and Xing, S and Zhao, X and Wu, F}, title = {Effects of BBIBP-CorV vaccine on gut microbiota and short-chain fatty acids in mice exposed to bis (2-ethylhexyl) phthalate and dioctyl terephthalate.}, journal = {Environment international}, volume = {190}, number = {}, pages = {108851}, doi = {10.1016/j.envint.2024.108851}, pmid = {38941942}, issn = {1873-6750}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Phthalic Acids ; *Fatty Acids, Volatile/metabolism ; *Diethylhexyl Phthalate/toxicity ; COVID-19 Vaccines ; COVID-19/prevention &amp; control ; SARS-CoV-2/immunology ; Male ; Plasticizers/toxicity ; Female ; Vaccines, Inactivated ; }, abstract = {As the COVID-19 pandemic has progressed, increasing evidences suggest that the gut microbiota may play a crucial role in the effectiveness of SARS-CoV-2 vaccine. Thus, this study was aimed at investigating the influence of SARS-CoV-2 vaccine on the gut microbiota and short-chain fatty acids (SCFAs) of organisms exposed to environmental contaminants, i.e., plasticizers: phthalate esters. We found that in mice, exposure to dioctyl terephthalate (DOTP) and bis -2-ethylhexyl phthalate (DEHP) decreased the blood glucose level and white fat weight, induced inflammatory responses, caused damage to liver and intestinal tissues, and disrupted the gut microbiota composition and SCFAs metabolism. Specifically, the Bacteroidetes phylum was positively correlated with BBIBP-CorV vaccine, while acetic acid was negatively associated with the vaccine. Interestingly, the BBIBP-CorV vaccine somewhat alleviated tissue inflammation and reduced the contents of acetic acid and propionic acid in mice exposed to DEHP and DOTP. These findings were confirmed by a fecal microbiota transplantation assay. Overall, this study revealed that exposure to DEHP and DOTP adversely affects the gut microbiota and SCFAs, while the BBIBP-CorV vaccine can protect mice against these effects. This work highlighted the relationship between BBIBP-CorV vaccination, gut microbiome composition, and responses to plasticizers, which may facilitate the development and risk assessment of SARS-CoV-2 vaccines and environmental contaminants on microbiota health.}, }
@article {pmid38941818, year = {2024}, author = {Yang, S and Wei, Z and Luo, J and Wang, X and Chen, G and Guan, X and She, Z and Liu, W and Tong, Y and Liu, H and Wen, M and Chen, H and Zhu, P and Li, G and Wang, D and Huang, L and Xu, S and Chen, D and Zhang, Q and Wei, Y}, title = {Integrated bioinformatics and multiomics reveal Liupao tea extract alleviating NAFLD via regulating hepatic lipid metabolism and gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {132}, number = {}, pages = {155834}, doi = {10.1016/j.phymed.2024.155834}, pmid = {38941818}, issn = {1618-095X}, mesh = {Animals ; *Non-alcoholic Fatty Liver Disease/drug therapy ; *Gastrointestinal Microbiome/drug effects ; *Lipid Metabolism/drug effects ; Male ; Mice ; *Liver/drug effects/metabolism ; Plant Extracts/pharmacology ; Mice, Inbred C57BL ; Computational Biology ; Molecular Docking Simulation ; Disease Models, Animal ; Tea/chemistry ; Network Pharmacology ; Multiomics ; }, abstract = {BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) poses a significant global public health concern. Liupao tea (LPT) is a Chinese national geographical indication product renowned for its lipid-lowering properties. However, the precise mechanisms and active constituents contributing to the efficacy of LPT against NAFLD remain unclear.<br><br>PURPOSE: This study aims to comprehensively explore the therapeutic potential of Liupao tea extract (LPTE) in alleviating NAFLD through an integrated strategy.<br><br>METHODS: Initially, network pharmacology analysis was conducted based on LPTE chemical ingredient analysis, identifying core targets and key components. Potential active ingredients were validated through chemical standards based on LC-MS/MS. To confirm the pharmacological efficacy of LPTE in NAFLD, NAFLD mice models were employed. Alterations in hepatic lipid metabolism were comprehensively elucidated through integration of metabolomics, lipidomics, network pharmacology analysis, and real-time PCR analysis. To further explore the binding interactions between key components and core targets, molecular docking and microscale thermophoresis (MST) analysis were employed. Furthermore, to investigate LPTE administration effectiveness on gut microbiota in NAFLD mice, a comprehensive approach was employed. This included Metorigin analysis, 16S rRNA sequencing, molecular docking, and fecal microbiome transplantation (FMT).<br><br>RESULTS: Study identified naringenin, quercetin, luteolin, and kaempferol as the potential active ingredients of LPTE. These compounds exhibited therapeutic potential for NAFLD by targeting key proteins such as PTGS2, CYP3A4, and ACHE, which are involved in the metabolic pathways of hepatic linoleic acid (LA) and glycerophospholipid (GP) metabolism. The therapeutic effectiveness of LPTE was observed to be comparable to that of simvastatin. Furthermore, LPTE exhibited notable efficacy in alleviating NAFLD by influencing alterations in gut microbiota composition (Proteobacteria phylum, Lactobacillus and Dubosiella genus) that perhaps impact LA and GP metabolic pathways.<br><br>CONCLUSION: LPTE could be effective in preventing high-fat diet (HFD)-induced NAFLD by modulating hepatic lipid metabolism and gut microbiota. This study firstly integrated bioinformatics and multi-omics technologies to identify the potential active components and key microbiota associated with LPTE's effects, while also primally elucidating the action mechanisms of LPTE in alleviating NAFLD. The findings offer a conceptual basis for LPTE's potential transformation into an innovative pharmaceutical agent for NAFLD prevention.}, }
@article {pmid38940400, year = {2024}, author = {Zhong, HJ and Zhuang, YP and Xie, X and Song, JY and Wang, SQ and Wu, L and Zhan, YQ and Wu, Q and He, XX}, title = {Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2372881}, pmid = {38940400}, issn = {1949-0984}, mesh = {Animals ; *Receptors, CXCR6/metabolism ; *Chemokine CXCL16/metabolism ; Mice ; *Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; *Liver/metabolism/microbiology ; Lymphocytes/immunology/metabolism ; Mice, Inbred C57BL ; Male ; Immunity, Innate ; Fatty Liver/therapy/metabolism/microbiology ; Interleukin-22 ; Non-alcoholic Fatty Liver Disease/therapy/microbiology/metabolism/immunology ; Interleukins/metabolism ; Female ; }, abstract = {Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.}, }
@article {pmid38940030, year = {2024}, author = {Li, Y and Fang, Y and Wang, H and Zhang, H}, title = {Balancing Act: Exploring the Gut Microbiota-Brown Adipose Tissue Axis in PCOS Pathogenesis and Therapeutic Frontiers.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {29}, number = {6}, pages = {208}, doi = {10.31083/j.fbl2906208}, pmid = {38940030}, issn = {2768-6698}, support = {2023YFC2705400//National Key Research and Development Program of China/ ; }, mesh = {*Polycystic Ovary Syndrome/microbiology/metabolism/therapy/physiopathology ; Humans ; Female ; *Gastrointestinal Microbiome/physiology ; *Adipose Tissue, Brown/metabolism ; Animals ; Insulin Resistance ; Fecal Microbiota Transplantation ; Obesity/microbiology/metabolism/therapy ; }, abstract = {Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence. Hyperandrogenemia and insulin resistance are two key pathophysiological factors that contribute to PCOS, both of which contribute to a variety of health issues such as menstrual irregularities, obesity, dysfunctional glucose and lipid homeostasis, infertility, mental disorders, and cardiovascular and cerebrovascular diseases. Despite ongoing studies, the origin and pathogenesis of PCOS remain elusive; there is also a clinical need for simpler, more effective, longer lasting, and more comprehensive treatments for women with PCOS. The gut-fat axis, a critical regulatory route for metabolism, endocrine function, and immune response, has received considerable interest in recent years in the research of the etiology and treatment of metabolic illnesses such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. The latest research in PCOS has revealed significant alterations in the homogeneity and phylogenetic diversity of the gut microbiota. Animal research using fecal microbiota transplantation has confirmed the importance of gut microbiota in regulating insulin sensitivity and sex hormone balance in PCOS. Furthermore, studies have shown a decrease in the volume and/or activity of brown adipose tissue (BAT) in PCOS patients, a change that alters adipokine release, leading to insulin resistance and hyperandrogenemia, aggravating PCOS progression. Given the function of BAT in increasing energy expenditure and alleviating metabolic parameters, efforts to activate BAT or induce browning of white adipose tissue have emerged as possible treatments for PCOS. Recent research has suggested that the gut microbiota can influence BAT creation and activity via metabolites such as short-chain fatty acids and bile acids, as well as the gut-brain axis. Cold exposure, healthy dieting, metformin, bariatric surgery, glucagon-like peptide 1 receptor agonists and melatonin have all been shown in basic and clinical studies to modulate BAT activity by influencing the gut microbiota, demonstrating significant clinical potential. However, more studies into the regulation mechanisms of the gut-BAT axis are required to produce more effective, comfortable, and safe tailored therapeutics for PCOS.}, }
@article {pmid38938213, year = {2024}, author = {Wu, Y and Gu, D and Li, J and Li, J and Hou, G}, title = {Role of the gut microbiota in cefoperazone/sulbactam-induced epilepsy in mice with chronic renal failure.}, journal = {Renal failure}, volume = {46}, number = {2}, pages = {2371551}, pmid = {38938213}, issn = {1525-6049}, mesh = {Animals ; *Cefoperazone/therapeutic use ; *Sulbactam/therapeutic use ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Disease Models, Animal ; *Kidney Failure, Chronic/therapy/complications ; *Epilepsy/drug therapy ; Male ; Anti-Bacterial Agents/adverse effects ; Fecal Microbiota Transplantation ; Feces/microbiology ; }, abstract = {OBJECTIVES: The mechanism of cefoperazone/sulbactam-induced epilepsy in chronic kidney disease (CKD) patients is not yet clear. We hypothesized that cefoperazone/sulbactam-induced epilepsy could be based on two main factors: neurotoxicity caused by drug accumulation after renal failure and an abnormal gut microbiota (GM).<br><br>METHODS: A chronic renal failure (CRF) model in mice was established, and then different doses of cefoperazone/sulbactam were injected to induce epilepsy in mice. Normal mouse feces for fecal microbiota transplantation (FMT) were collected. We observed the changes in feces, mental state, and activity of each group of mice. After killing, we collected kidneys and colon for H&amp;E staining. We collected mouse feces for the 16S RNA sequencing of bacteria.<br><br>RESULTS: All CRF mice injected with different concentrations of cefoperazone/sulbactam experienced grade-V seizures and eventually died, whereas normal control mice did not. However, after FMT intervention, the time of epilepsy onset and death in mice was delayed. Early FMT intervention resulted in more mice surviving (p&#xa0;=&#xa0;.0359). Moreover, the villi in the mucosal of group-CS layer fell off, goblet cells missed, and crypts disappeared. The mucosal layer and submucosa were clearly separated. The morphology of intestinal tissue of the CFS and FS group was improved. After FMT, the changes of the GM were observed.<br><br>CONCLUSIONS: The GM may be involved in the epilepsy induced by cefoperazone/sulbactam in CRF mice. FMT can delay the onset of epilepsy in CRF mice induced by cefoperazone/sulbactam, and the earlier the intervention, the better the effect.}, }
@article {pmid38935618, year = {2024}, author = {Sun, J and Teng, M and Zhu, W and Zhao, X and Zhao, L and Li, Y and Zhang, Z and Liu, Y and Bi, S and Wu, F}, title = {MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.}, journal = {ACS nano}, volume = {18}, number = {27}, pages = {18085-18100}, doi = {10.1021/acsnano.4c06298}, pmid = {38935618}, issn = {1936-086X}, mesh = {Animals ; Male ; *MicroRNAs/genetics/metabolism ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Paternal Exposure/adverse effects ; *Testis/drug effects/metabolism/pathology ; *Nanoparticles/chemistry ; Polyethylene/toxicity ; Spermatogenesis/drug effects ; }, abstract = {Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F0 and F1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F0 and F1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.}, }
@article {pmid38935586, year = {2024}, author = {Colt, SF and Choi, RJ and Wexler, A}, title = {To Counsel or Not to Counsel: Physician Attitudes and Experiences with Do-It-Yourself (DIY) Fecal Microbiota Transplant (FMT).}, journal = {AJOB empirical bioethics}, volume = {15}, number = {4}, pages = {324-335}, pmid = {38935586}, issn = {2329-4523}, support = {DP5 OD026420/OD/NIH HHS/United States ; }, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Attitude of Health Personnel ; Female ; Male ; *Physicians ; *Qualitative Research ; Middle Aged ; Adult ; Counseling ; }, abstract = {BACKGROUND: In the early 2010s, a phenomenon known as do-it-yourself (DIY) fecal microbiota transplant (FMT) emerged as lay individuals began self-administering FMTs at home. Although prior research indicates that many individuals who perform DIY FMT have sought advice from healthcare providers, to date there has been no investigation of physicians' experiences with DIY FMT. The objective of this qualitative study was to examine the attitudes of physicians who offer FMT regarding the practice of DIY FMT and to assess how they navigated the ethical challenges of patient requests for DIY FMT.<br><br>METHODS: We recruited physicians listed on two patient-created online databases of FMT providers. All physicians who indicated having been approached for advice about DIY FMT were included in the study. Semi-structured interviews with physicians explored their attitudes toward and experiences with DIY FMT.<br><br>RESULTS: Of 18 physicians interviewed, one reported having provided counsel in response to an initial patient inquiry about DIY FMT, 2 indicated they explicitly advised against DIY FMT and refused to provide advice, and 15 fell in a middle category of discouraging DIY FMT and discussing reasons why. Among the physicians in this third category, four reported that they had changed their approach to providing counsel in response to a patient telling them they were going to perform DIY FMT anyway.<br><br>CONCLUSIONS: Physicians in our study employed a wide range of strategies for promoting safety in the DIY FMT context, from explicitly advising against the procedure to the provision of guidance aimed at mitigating potential harms. While there has been increasing attention to the practices of DIY medicine, this study underscores the need for greater attention to the ethically complex situations that physicians face when patients request guidance for unapproved at-home treatments.}, }
@article {pmid38934721, year = {2024}, author = {Kooij, KL and Andreani, NA and van der Gun, LL and Keller, L and Trinh, S and van der Vijgh, B and Luijendijk, M and Dempfle, A and Herpertz-Dahlmann, B and Seitz, J and van Elburg, A and Danner, UN and Baines, J and Adan, RAH}, title = {Fecal microbiota transplantation of patients with anorexia nervosa did not alter flexible behavior in rats.}, journal = {The International journal of eating disorders}, volume = {57}, number = {9}, pages = {1868-1881}, doi = {10.1002/eat.24231}, pmid = {38934721}, issn = {1098-108X}, support = {//NWO-ALW Open Competition grant/ ; MIGBANFKZ//ERA-NET neuron 2018/ ; 01EW1906A//ERA-NET neuron 2018/ ; 01EW1906A-01EW1906B//ERA-NET neuron 2018/ ; BA 2863/14-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Anorexia Nervosa/therapy ; Rats ; Humans ; Female ; Anxiety/therapy ; Behavior, Animal ; Gastrointestinal Microbiome ; Reversal Learning ; Ventral Tegmental Area ; Dysbiosis/therapy ; Adult ; Disease Models, Animal ; Dopamine/metabolism ; }, abstract = {OBJECTIVE: Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression.<br><br>METHODS: In a preclinical study, we explored whether AN-derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase-cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety-like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests.<br><br>RESULTS: Neither antibiotic-induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose-stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients.<br><br>DISCUSSION: No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic-induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies.<br><br>PUBLIC SIGNIFICANCE: While our study did not reveal direct impacts of AN-associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic-induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa.}, }
@article {pmid38934542, year = {2024}, author = {Yang, X and Xu, Y and Li, J and Ran, X and Gu, Z and Song, L and Zhang, L and Wen, L and Ji, G and Wang, R}, title = {Bile acid-gut microbiota imbalance in cholestasis and its long-term effect in mice.}, journal = {mSystems}, volume = {9}, number = {7}, pages = {e0012724}, pmid = {38934542}, issn = {2379-5077}, support = {No. 82004149//MOST | National Natural Science Foundation of China (NSFC)/ ; R01 DK130318/DK/NIDDK NIH HHS/United States ; R01 DK126809/DK/NIDDK NIH HHS/United States ; P30 DK045735/DK/NIDDK NIH HHS/United States ; HD 097808, DK 126809, DK 130318//HHS | National Institutes of Health (NIH)/ ; 2021044//The International postdoctoral Exchange Fellowship/ ; R01 HD097808/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Bile Acids and Salts/metabolism ; *Cholestasis/microbiology/metabolism ; Mice ; *Dysbiosis/microbiology ; Male ; *Mice, Inbred C57BL ; Liver/metabolism/microbiology/pathology ; Disease Models, Animal ; }, abstract = {UNLABELLED: Cholestasis is a common morbid state that may occur in different phases; however, a comprehensive evaluation of the long-term effect post-recovery is still lacking. In the hepatic cholestasis mouse model, which was induced by a temporary complete blockage of the bile duct, the stasis of bile acids and liver damage typically recovered within a short period. However, we found that the temporary hepatic cholestasis had a long-term effect on gut microbiota dysbiosis, including overgrowth of small intestinal bacteria, decreased diversity of the gut microbiota, and an overall imbalance in its composition accompanied by an elevated inflammation level. Additionally, we observed an increase in Escherichia-Shigella (represented by ASV136078), rich in virulence factors, in both small and large intestines following cholestasis. To confirm the causal role of dysregulated gut microbiota in promoting hepatic inflammation and injury, we conducted gut microbiota transplantation into germ-free mice. We found that recipient mice transplanted with feces from cholestasis mice exhibited liver inflammation, damage, and accumulation of hepatic bile acids. In conclusion, our study demonstrates that cholestasis disrupts the overall load and structural composition of the gut microbiota in mice, and these adverse effects persist after recovery from cholestatic liver injury. This finding suggests the importance of monitoring the structural composition of the gut microbiota in patients with cholestasis and during their recovery.<br><br>IMPORTANCE: Our pre-clinical study using a mouse model of cholestasis underscores that cholestasis not only disrupts the equilibrium and structural configuration of the gut microbiota but also emphasizes the persistence of these adverse effects even after bile stasis restoration. This suggests the need of monitoring and initiating interventions for gut microbiota structural restoration in patients with cholestasis during and after recovery. We believe that our study contributes to novel and better understanding of the intricate interplay among bile acid homeostasis, gut microbiota, and cholestasis-associated complications. Our pre-clinical findings may provide implications for the clinical management of patients with cholestasis.}, }
@article {pmid38934224, year = {2024}, author = {Pereira, LTG and Vilela, WR and Bellozi, PMQ and Engel, DF and de Paula, GC and de Andrade, RR and Mortari, MR and de Melo Teixeira, M and Coleine, C and Figueiredo, CP and de Bem, AF and Amato, AA}, title = {Fecal microbiota transplantation ameliorates high-fat diet-induced memory impairment in mice.}, journal = {Journal of neurochemistry}, volume = {168}, number = {9}, pages = {2893-2907}, doi = {10.1111/jnc.16156}, pmid = {38934224}, issn = {1471-4159}, support = {408703/2021-0//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 424809-2018-4//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 00193-00000229/2021-21//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; 00193-00000889/2021-10//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; 00193-00001324/2019-27//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; 485489/2014-1//Instituto Nacional de Ci&#xea;ncia e Tecnologia e NeuroImunomodula&#xe7;&#xe3;o/ ; }, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Fecal Microbiota Transplantation/methods ; Male ; *Mice, Inbred C57BL ; *Memory Disorders/prevention &amp; control/etiology ; Mice ; *Gastrointestinal Microbiome/physiology ; Hippocampus ; Glucose Intolerance ; }, abstract = {Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high-fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3-day fecal microbiota transplantation (FMT) regimen from low-fat (control) diet-fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect. Improvement in recognition memory by FMT was accompanied by decreased HFD-induced astrogliosis in the hippocampal cornu ammonis region. Gut microbiome composition analysis indicated that HFD diminished microbiota diversity compared to control diet, whereas FMT partially restored the phyla diversity. Our findings reinforce the role of the gut microbiota on HFD-induced cognitive impairment and suggest that modulating the gut microbiota may be an effective strategy to prevent metabolic and cognitive dysfunction associated with unfavorable dietary patterns.}, }
@article {pmid38932733, year = {2024}, author = {Kalra, S and Sharma, S and Verma, SK and Thakor, P and Malve, H and Chamle, V and Patil, A and Meer, T and Naik, I}, title = {Assessment of Hydration Status Using Conventional Method and Salivary Osmolarity as a Point-of-care Tool.}, journal = {The Journal of the Association of Physicians of India}, volume = {72}, number = {6S}, pages = {30-38}, doi = {10.59556/japi.72.0545}, pmid = {38932733}, issn = {0004-5772}, mesh = {Humans ; *Saliva/chemistry ; Osmolar Concentration ; *Dehydration/diagnosis ; Biomarkers/analysis ; Point-of-Care Systems ; Organism Hydration Status/physiology ; Point-of-Care Testing ; }, abstract = {Dehydration is a well-known problem worldwide, and its assessment can be challenging due to confusing physical signs. The most effective way to assess hydration status is through the costly stable isotope methodology, but this approach has practical limitations. More commonly accepted and utilized indicators of hydration status are hematological and urinary parameters. However, hematological markers require invasive methods, and urinary markers have varying degrees of success in tracking hydration changes. While alterations in body weight can serve as a means of promptly evaluating hydration status, various factors such as food consumption, fluid intake, fecal losses, and urine production can impact these changes. Researchers have turned their attention to saliva as a potential marker and point-of-care (POC) testing to address the limitations of existing biomarkers. Saliva is appealing due to its easy collection process and similarities to extracellular fluid in terms of water and ion concentrations. Recent studies have shown that saliva flow rate, osmolarity/osmolality, and total protein concentration can effectively monitor changes in body mass during acute dehydration. Misdiagnosing dehydration can have severe clinical consequences, leading to morbidity and even mortality. This narrative review focuses on recognizing the significance of hydration assessment, monitoring, and the potential of salivary osmolarity (SOSM) as an assessment tool. Healthcare professionals can improve their practices and interventions to optimize hydration and promote overall wellness using such tools.}, }
@article {pmid38931292, year = {2024}, author = {Młynarska, E and Wasiak, J and Gajewska, A and Steć, G and Jasińska, J and Rysz, J and Franczyk, B}, title = {Exploring the Significance of Gut Microbiota in Diabetes Pathogenesis and Management-A Narrative Review.}, journal = {Nutrients}, volume = {16}, number = {12}, pages = {}, pmid = {38931292}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/microbiology/therapy ; *Probiotics/therapeutic use ; *Prebiotics/administration &amp; dosage ; *Dysbiosis/therapy ; *Fecal Microbiota Transplantation ; Animals ; }, abstract = {Type 2 diabetes is a disease with significant health consequences for the individual. Currently, new mechanisms and therapeutic approaches that may affect this disease are being sought. One of them is the association of type 2 diabetes with microbiota. Through the enteric nervous system and the gut-microbiota axis, the microbiota affects the functioning of the body. It has been proven to have a real impact on influencing glucose and lipid metabolism and insulin sensitivity. With dysbiosis, there is increased bacterial translocation through the disrupted intestinal barrier and increased inflammation in the body. In diabetes, the microbiota's composition is altered with, for example, a more abundant class of Betaproteobacteria. The consequences of these disorders are linked to mechanisms involving short-chain fatty acids, branched-chain amino acids, and bacterial lipopolysaccharide, among others. Interventions focusing on the gut microbiota are gaining traction as a promising approach to diabetes management. Studies are currently being conducted on the effects of the supply of probiotics and prebiotics, as well as fecal microbiota transplantation, on the course of diabetes. Further research will allow us to fully develop our knowledge on the subject and possibly best treat and prevent type 2 diabetes.}, }
@article {pmid38926934, year = {2024}, author = {Abrahamsson, T}, title = {We need more evidence about the risks and benefits of giving children faecal microbiota transplants.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {113}, number = {9}, pages = {1987-1988}, doi = {10.1111/apa.17339}, pmid = {38926934}, issn = {1651-2227}, mesh = {Humans ; *Fecal Microbiota Transplantation ; Child ; Risk Assessment ; }, }
@article {pmid38925098, year = {2024}, author = {Barron, M and Fernando, DG and Atkinson, SN and Kirby, J and Kindel, TL}, title = {Sleeve Gastrectomy Protects Against Hypertension in Rats due to Changes in the Gut Microbiome.}, journal = {The Journal of surgical research}, volume = {301}, number = {}, pages = {118-126}, pmid = {38925098}, issn = {1095-8673}, support = {K08 HL140000/HL/NHLBI NIH HHS/United States ; R01 HL158900/HL/NHLBI NIH HHS/United States ; }, mesh = {Male ; Rats ; *Blood Pressure/physiology ; Body Weight/physiology ; Disease Models, Animal ; Eating/physiology ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrectomy/instrumentation/methods ; *Gastrointestinal Microbiome/physiology ; Genetic Variation ; Glucose Tolerance Test ; *Hypertension/etiology/microbiology/surgery ; *Obesity/complications/microbiology/surgery ; Postoperative Period ; Random Forest ; Rats, Zucker ; RNA, Ribosomal, 16S ; Animals ; }, abstract = {INTRODUCTION: Sleeve gastrectomy (SG), results in improvement in hypertension. We have previously published that rodent SG improves hypertension independent of weight loss associated with unique shifts in the gut microbiome. We tested if the gut microbiome directly improves blood pressure by performing fecal material transfer (FMT) from post-SG rats to surgery-naïve animals.<br><br>METHODS: We performed SG or Sham surgery in male, Zucker rats (n&#xa0;=&#xa0;6-7) with obesity. Stool was collected postop from surgical donors for treatment of recipient rats. Three nonsurgical groups received daily, oral consumption of SG stool, sham stool, or vehicle alone (Nutella) for 10&#xa0;wk (n&#xa0;=&#xa0;7-8). FMT treatment was assessed for effects on body weight, food intake, oral glucose tolerance, and blood pressure. Genomic deoxyribonucleic acid of stool from donor and recipient groups were sequenced by 16S ribosomal ribonucleic acid and analyzed for diversity, abundance, and importance.<br><br>RESULTS: Ten&#xa0;weeks of SG-FMT treatment significantly lowered systolic blood pressures in surgery-na&#xef;ve, recipient rats compared to vehicle treatment alone (126.8&#xa0;&#xb1;&#xa0;13.3&#xa0;mmHg versus 151.8&#xa0;&#xb1;&#xa0;12.2&#xa0;mmHg, P&#xa0;=&#xa0;0.001). SG-FMT treatment also significantly altered beta diversity metrics compared to Sham-FMT and vehicle treatment. In random forest analysis, amplicon sequence variant level significantly predicted FMT group, P&#xa0;=&#xa0;0.01.<br><br>CONCLUSIONS: We have found a direct link between gut microbial changes after SG and regulation of blood pressure. Future mechanistic studies are required to learn what specific gut microbial changes are required to induce improvements in obesity-associated hypertension and translation to clinical, metabolic surgery.}, }
@article {pmid38922808, year = {2024}, author = {Mullish, BH and Thursz, MR}, title = {Alcohol-associated liver disease: Emerging therapeutic strategies.}, journal = {Hepatology (Baltimore, Md.)}, volume = {80}, number = {6}, pages = {1372-1389}, pmid = {38922808}, issn = {1527-3350}, support = {MR/R014019/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Liver Diseases, Alcoholic/therapy ; Liver Transplantation ; Hepatitis, Alcoholic/therapy ; Fecal Microbiota Transplantation ; }, abstract = {The large and growing burden of alcohol-associated liver disease-and the considerable burden of morbidity and mortality associated with it-has been a drive toward ongoing research into novel strategies for its treatment, with a particular focus upon alcohol-associated hepatitis (AH). Management of alcohol-use disorder forms the central pillar of alcohol-associated liver disease care, with evidence-based psychological and pharmacological approaches being well established, and certain models demonstrating improved clinical outcomes when hepatology and addiction services are co-located. Corticosteroids have previously been used somewhat indiscriminately in patients with severe AH, but effective tools now exist to assess early response (and limit futile ongoing exposure). Techniques to predict risk of corticosteroid-related infection are also available, although current clinical strategies to mitigate this risk are limited. A variety of novel therapeutic approaches to AH are at different phases of trials and evidence gathering, with some of the most promising signals related to cytokine manipulation, epigenetic modulation, and targeting of the gut microbiota (ie, by means of fecal microbiota transplant). While remaining an ongoing source of debate, early liver transplant in severe AH has grown in interest and acceptability over the past decade as evidence supporting its efficacy builds, in the process challenging paradigms about mandatory pretransplant sobriety periods. However, uncertainty remains regarding the optimal selection criteria, and whether liver transplant has a role for only a highly limited proportion of patients with AH or more widespread application. This review aims to provide an overview of this fast-moving field.}, }
@article {pmid38922353, year = {2024}, author = {Ali, AQ and Sabir, DK and Dawood, AF and Abu-Rashed, M and Hasari, A and Gharqan, F and Alnefaie, S and Mohiddin, LE and Tatry, MM and Albadan, DA and Alyami, MM and Almutairi, MF and Shawky, LM}, title = {The potential liver injury induced by metronidazole-provoked disturbance of gut microbiota: modulatory effect of turmeric supplementation.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {397}, number = {12}, pages = {9845-9858}, pmid = {38922353}, issn = {1432-1912}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Curcuma ; Male ; *Chemical and Drug Induced Liver Injury/pathology/prevention &amp; control ; *Metronidazole/pharmacology/toxicity ; *Liver/drug effects/pathology/metabolism ; Rats ; Rats, Sprague-Dawley ; Plant Extracts/pharmacology ; Fecal Microbiota Transplantation ; Dietary Supplements ; Cytokines/metabolism ; }, abstract = {It has been reported that the gut-liver axis and intestinal microbiome contribute crucially to different liver diseases. So, targeting this hepato-intestinal connection may provide a novel treatment modality for hepatic disorders such as drug-induced liver injury (DILI). The present study thought to investigate the protective effect of turmeric (TUR) on metronidazole (MNZ)-induced liver damage and the possible association of the gut-liver axis and gut microbiota as a suggested underlying mechanism. In the first experiment, a MNZ-induced liver injury rat model was reproduced after 130 mg/kg oral MNZ administration for 30 days. Meanwhile, the treatment group was orally treated with 100 mg/kg turmeric daily. In the second experiment, fecal microbiome transplantation (FMT) was conducted, in which the fecal microbiome of each group in the first experiment was transplanted to a healthy corresponding group in the second experiment. The liver enzymes (aminotransferase (ALT) and aspartate aminotransferase (AST)) and histopathological examination were estimated to assess liver function. Inflammatory cytokines and oxidative markers were evaluated in the liver tissues. Histological analysis, intestinal barrier markers, and expression of tight junction proteins were measured for assessment of the intestinal injury. Changes in the gut microbial community and possible hepatic bacterial transmission were analyzed using 16S rRNA sequencing. MNZ induced intestinal and liver injuries which were significantly improved by turmeric. Increased firmicutes/bacteroidetes ratio and bacterial transmission due to gut barrier disruption were suggested. Moreover, TUR has maintained the gut microbial community by rebalancing and restoring bacterial proportions and abundance, thereby repairing the gut mucosal barrier and suppressing bacterial translocation. TUR protected against MNZ-induced gut barrier disruption. Reshaping of the intestinal bacterial composition and prohibition of the hepatic microbial translocation were suggested turmeric effects, potentially mitigating MNZ-related liver toxicity.}, }
@article {pmid38920288, year = {2024}, author = {Liang, F and Song, Y and Lin, D and He, H and Xu, J and He, X and Wu, L}, title = {Washed Microbiota Transplantation Is Associated With Improved Lipid Profiles: Long-Term Efficacy and Safety in an Observational Cohort From South China.}, journal = {Clinical and translational gastroenterology}, volume = {15}, number = {7}, pages = {e00735}, pmid = {38920288}, issn = {2155-384X}, support = {2023M740782//China postdoctoral science foundation/ ; B2022209//Medical Scientific Research Foundation of Guangdong Province/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; China/epidemiology ; *Hyperlipidemias/blood/therapy/complications ; Treatment Outcome ; *Lipids/blood ; Adult ; *Fecal Microbiota Transplantation ; Triglycerides/blood ; Aged ; Dyslipidemias/blood/therapy ; Cholesterol, LDL/blood ; Gastrointestinal Microbiome ; }, abstract = {INTRODUCTION: Dyslipidemia is one of the main risk factors of chronic metabolic diseases. Our previous studies have shown that washed microbiota transplantation (WMT) has a significant improvement effect on patients with hyperlipidemia and hypolipemia in the Chinese population. The purpose of this study was to further explore the long-term efficacy and safety of WMT in patients with hyperlipidemia.<br><br>METHODS: Clinical data of patients who received WMT for multicourse were collected. Changes of blood lipid indexes before and after WMT, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein A, and Apolipoprotein B.<br><br>RESULTS: A total of 124 patients were enrolled, including 56 cases in the hyperlipidemia group and 68 cases with normal lipids. The mean observation time was 787.80 &#xb1; 371.45 days, and the longest follow-up time was 1,534 days. TC and non-HDL-C in the hyperlipidemia group with 1-4 courses of WMT were significantly reduced (P < 0.05); TG decreased significantly after the second course (P < 0.05); low-density lipoprotein cholesterol also significantly decreased after the fourth course of treatment (P < 0.05); TG, TC, and non-HDL-C significantly decreased in single course, double course, and multiple course, respectively (P < 0.05). In terms of time period, over 1 year, the improvement in multicourse treatment was more significant than the single and double-course ones. In terms of comprehensive efficacy, WMT restored 32.14% of patients in the hyperlipidemia group to the normal lipid group (P < 0.001), of which 30.00% recovered to the normal lipid group within 1 year (P = 0.004) and 65.38% were reassigned to the normal lipid group over 1 year (P = 0.003). In addition, over the 1-year treatment period, WMT significantly degraded the high-risk and medium-risk groups of atherosclerotic cardiovascular disease risk stratification in hyperlipidemia cases. There were no serious adverse events.<br><br>DISCUSSION: WMT had a long-term improvement effect on patients with hyperlipidemia. The effect of multiple courses over 1 year was more significant than that of single/double courses and also had a significant destratification effect on the risk of atherosclerotic cardiovascular disease with high safety. Therefore, WMT provides a safe and long-term effective clinical treatment for patients with dyslipidemia.}, }
@article {pmid38918470, year = {2024}, author = {Sinha, AK and Laursen, MF and Brinck, JE and Rybtke, ML and Hjørne, AP and Procházková, N and Pedersen, M and Roager, HM and Licht, TR}, title = {Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota.}, journal = {Nature microbiology}, volume = {9}, number = {8}, pages = {1964-1978}, pmid = {38918470}, issn = {2058-5276}, support = {19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 35040//Villum Fonden (Villum Foundation)/ ; }, mesh = {*Tryptophan/metabolism ; Animals ; Humans ; *Gastrointestinal Microbiome/physiology ; *Dietary Fiber/metabolism ; *Feces/microbiology ; Mice ; *Indoles/metabolism ; *Escherichia coli/metabolism ; *Clostridium/metabolism ; Germ-Free Life ; Propionates/metabolism ; Microbial Interactions ; Fecal Microbiota Transplantation ; }, abstract = {Tryptophan is catabolized by gut microorganisms resulting in a wide range of metabolites implicated in both beneficial and adverse host effects. How gut microbial tryptophan metabolism is directed towards indole, associated with chronic kidney disease, or towards protective indolelactic acid (ILA) and indolepropionic acid (IPA) is unclear. Here we used in vitro culturing and animal experiments to assess gut microbial competition for tryptophan and the resulting metabolites in a controlled three-species defined community and in complex undefined human faecal communities. The generation of specific tryptophan-derived metabolites was not predominantly determined by the abundance of tryptophan-metabolizing bacteria, but rather by substrate-dependent regulation of specific metabolic pathways. Indole-producing Escherichia coli and ILA- and IPA-producing Clostridium sporogenes competed for tryptophan within the three-species community in vitro and in vivo. Importantly, fibre-degrading Bacteroides thetaiotaomicron affected this competition by cross-feeding monosaccharides to E. coli. This inhibited indole production through catabolite repression, thus making more tryptophan available to C. sporogenes, resulting in increased ILA and IPA production. The fibre-dependent reduction in indole was confirmed using human faecal cultures and faecal-microbiota-transplanted gnotobiotic mice. Our findings explain why consumption of fermentable fibres suppresses indole production but promotes the generation of other tryptophan metabolites associated with health benefits.}, }
@article {pmid38915399, year = {2024}, author = {Zhang, H and Hong, Y and Wu, T and Ben, E and Li, S and Hu, L and Xie, T}, title = {Role of gut microbiota in regulating immune checkpoint inhibitor therapy for glioblastoma.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1401967}, pmid = {38915399}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Glioblastoma/immunology/drug therapy/therapy/microbiology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Brain Neoplasms/immunology/drug therapy/therapy/microbiology ; Animals ; Brain-Gut Axis/immunology ; Fecal Microbiota Transplantation ; Tumor Microenvironment/immunology/drug effects ; }, abstract = {Glioblastoma (GBM) is a highly malignant, invasive, and poorly prognosed brain tumor. Unfortunately, active comprehensive treatment does not significantly prolong patient survival. With the deepening of research, it has been found that gut microbiota plays a certain role in GBM, and can directly or indirectly affect the efficacy of immune checkpoint inhibitors (ICIs) in various ways. (1) The metabolites produced by gut microbiota directly affect the host's immune homeostasis, and these metabolites can affect the function and distribution of immune cells, promote or inhibit inflammatory responses, affect the phenotype, angiogenesis, inflammatory response, and immune cell infiltration of GBM cells, thereby affecting the effectiveness of ICIs. (2) Some members of the gut microbiota may reverse T cell function inhibition, increase T cell anti-tumor activity, and ultimately improve the efficacy of ICIs by targeting specific immunosuppressive metabolites and cytokines. (3) Some members of the gut microbiota directly participate in the metabolic process of drugs, which can degrade, transform, or produce metabolites, affecting the effective concentration and bioavailability of drugs. Optimizing the structure of the gut microbiota may help improve the efficacy of ICIs. (4) The gut microbiota can also regulate immune cell function and inflammatory status in the brain through gut brain axis communication, indirectly affecting the progression of GBM and the therapeutic response to ICIs. (5) Given the importance of gut microbiota for ICI therapy, researchers have begun exploring the use of fecal microbiota transplantation (FMT) to transplant healthy or optimized gut microbiota to GBM patients, in order to improve their immune status and enhance their response to ICI therapy. Preliminary studies suggest that FMT may enhance the efficacy of ICI therapy in some patients. In summary, gut microbiota plays a crucial role in regulating ICIs in GBM, and with a deeper understanding of the relationship between gut microbiota and tumor immunity, it is expected to develop more precise and effective personalized ICI therapy strategies for GBM, in order to improve patient prognosis.}, }
@article {pmid38915068, year = {2024}, author = {Yan, J and Zhou, G and Ren, R and Zhang, X and Zhang, N and Wang, Z and Peng, L and Yang, Y}, title = {Siderophore-harboring gut bacteria and fecal siderophore genes for predicting the responsiveness of fecal microbiota transplantation for active ulcerative colitis.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {589}, pmid = {38915068}, issn = {1479-5876}, support = {2015AA020701//National High-tech Research and Development Program/ ; 82200609//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology/genetics ; Male ; Female ; *Feces/microbiology ; *Fecal Microbiota Transplantation ; Adult ; Middle Aged ; *Gastrointestinal Microbiome/genetics ; *Siderophores/metabolism ; Treatment Outcome ; Bacteria/genetics ; Genes, Bacterial ; Gene Dosage ; ROC Curve ; }, abstract = {BACKGROUND: Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness.<br><br>METHODS: Patients with active UC (Mayo score&#x2009;&#x2265;&#x2009;3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8&#xa0;weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy.<br><br>RESULTS: Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P&#x2009;<&#x2009;0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P&#x2009;<&#x2009;0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness.<br><br>CONCLUSIONS: A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after&#xa0;FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.}, }
@article {pmid38914878, year = {2024}, author = {Leclercq, S and de Timary, P}, title = {Role of the Microbiome and the Gut-Brain Axis in Alcohol Use Disorder: Potential Implication for Treatment Development.}, journal = {Current topics in behavioral neurosciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/7854_2024_478}, pmid = {38914878}, issn = {1866-3370}, abstract = {The gut microbiota is constituted by trillions of microorganisms colonizing the human intestine. Studies conducted in patients with alcohol use disorder (AUD) have shown altered microbial composition related to bacteria, viruses, and fungi.This review describes the communication pathways between the gut and the brain, including the ones related to the bacterial metabolites, the inflammatory cytokines, and the vagus nerve. We described in more detail the gut-derived metabolites that have been shown to be implicated in AUD or that could potentially be involved in the development of AUD due to their immune and/or neuroactive properties, including tryptophan-derivatives, tyrosine-derivatives, short chain fatty acids.Finally, we discussed the potential beneficial effects of microbiome-based therapies for AUD such as probiotics, prebiotics, postbiotic, and phage therapy.}, }
@article {pmid38913690, year = {2024}, author = {Yu, C and Xu, D and Luo, Y and Jiao, J and Liu, G and Wang, F and Gao, Y and Sun, X and Lv, X and Wu, H and Kong, X}, title = {Osteopontin Depletion in Nonhematopoietic Cells Improves Outcomes in Septic Mice by Enhancing Antimicrobial Peptide Production.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {5}, pages = {e1146-e1157}, pmid = {38913690}, issn = {1537-6613}, support = {82070633//National Natural Science Foundation of China/ ; 20XD1403700//Program of Shanghai Academic/Technology Research Leader/ ; 2018ZX10725-504//National Key Sci-Tech Special Project of China/ ; }, mesh = {Animals ; *Osteopontin/metabolism ; *Sepsis/microbiology/therapy ; Mice ; *Gastrointestinal Microbiome/physiology ; *Antimicrobial Peptides/metabolism ; Mice, Knockout ; Bacterial Load ; Forkhead Box Protein O3/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Male ; Organoids/metabolism ; }, abstract = {Osteopontin (Opn) depletion can improve septic outcomes, but the underlying mechanism remains unknown. In this study, we demonstrated that nonhematopoietic but not hematopoietic Opn depletion improved septic outcomes. When compared with wild type mice, cohoused Opn-/- mice displayed enhanced production of antibacterial peptides (AMPs), decreased bacterial loads, and a distinct bacterial composition of gut microbiota. Fecal microbiota transplantation and OPN neutralization assay showed that Opn depletion could reduce bacterial loads and improve septic inflammation. By employing an intestinal organoid culture system, we proved that OPN neutralization in wild type organoids could inactivate AKT and decrease FOXO3a phosphorylation, resulting in enhanced AMP production, whereas OPN treatment in OPN-deficient organoids could activate AKT and increase FOXO3a phosphorylation, leading to reduced AMP production. Our findings identified OPN as a novel regulatory factor of AMP production to modulate bacterial loads and composition of gut microbiota, in turn affecting sepsis outcomes.}, }
@article {pmid38911589, year = {2024}, author = {Liu, H and Wei, Y and Xu, Z and Lin, H and Zhao, Y and Wang, S and Gao, F and Feng, N and Wolfe, AJ and Liu, F}, title = {Exploring Factors Affecting Acceptance of Fecal Microbiota Transplantation for Patients with Recurrent Urinary Tract Infections: a Descriptive Qualitative Study.}, journal = {Patient preference and adherence}, volume = {18}, number = {}, pages = {1257-1269}, pmid = {38911589}, issn = {1177-889X}, abstract = {PURPOSE: Patients with recurrent urinary tract infections face complex management challenges. Fecal microbiota transplantation is a superior treatment for chronic infectious diseases, but limited patient knowledge affects treatment decisions. This study aims to identify factors associated with hesitancy towards fecal microbiota transplantation among patients with recurrent urinary tract infections, to help physicians and nurses in providing accurate and useful information to patients.<br><br>PATIENTS AND METHODS: A descriptive qualitative approach was employed, utilizing semi-structured interviews conducted with patients experiencing recurrent urinary tract infections who expressed hesitancy towards fecal microbiota transplantation. The interviews took place between September 2021 and December 2022. Thematic analysis was conducted on the semi-structured interviews to identify perceived facilitators and barriers associated with fecal microbiota transplantation.<br><br>RESULTS: The analysis included interviews with thirty adult female patients with recurrent urinary tract infections. Four facilitators influencing patients' decision-making regarding fecal microbiota transplantation were identified: (1) the motivating role of hope and expectations for active patient participation; (2) the influence of healthcare providers, as well as family members and friends on patients' decisions to pursue fecal microbiota transplantation; (3) the patients' perception of fecal microbiota transplantation as a low-risk treatment option; and (4) the dedication to the advancement of medical treatments. In contrast, two primary barriers to accepting fecal microbiota transplantation were identified: (1) that conventional treatment controls disease activity, while fecal microbiota transplantation effects remain uncertain; and (2) that safety concerns surrounding fecal microbiota transplantation.<br><br>CONCLUSION: Comprehensive information about fecal microbiota transplantation, including donor selection, sample processing, the procedure, and potential discomfort, is essential for patients and families to make informed treatment decisions.<br><br>REGISTRATION: CHiCTR2100048970.}, }
@article {pmid38910461, year = {2024}, author = {Wu, B and Quan, C and He, Y and Matsika, J and Huang, J and Liu, B and Chen, J}, title = {Targeting gut and intratumoral microbiota: a novel strategy to improve therapy resistance in cancer with a focus on urologic tumors.}, journal = {Expert opinion on biological therapy}, volume = {24}, number = {8}, pages = {747-759}, doi = {10.1080/14712598.2024.2371543}, pmid = {38910461}, issn = {1744-7682}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; Animals ; *Urologic Neoplasms/microbiology/immunology/therapy/drug therapy ; *Tumor Microenvironment/immunology ; *Drug Resistance, Neoplasm ; Fecal Microbiota Transplantation ; Microbiota/drug effects ; }, abstract = {INTRODUCTION: Growing attention has been drawn to urologic tumors due to their rising incidence and suboptimal clinical treatment outcomes. Cancer therapy resistance poses a significant challenge in clinical oncology, limiting the efficacy of conventional treatments and contributing to disease progression. Recent research has unveiled a complex interplay between the host microbiota and cancer cells, highlighting the role of the microbiota in modulating therapeutic responses.<br><br>AREAS COVERED: We used the PubMed and Web of Science search engines to identify key publications in the fields of tumor progression and urologic tumor treatment, specifically focusing on the role of the microbiota. In this review, we summarize the current literature on how microbiota influence the tumor microenvironment and anti-tumor immunity, as well as their impact on treatments for urinary system malignancies, highlighting promising future applications.<br><br>EXPERT OPINION: We explore how the composition and function of the gut microbiota influence the tumor microenvironment and immune response, ultimately impacting treatment outcomes. Additionally, we discuss emerging strategies targeting the microbiota to enhance therapeutic efficacy and overcome resistance. The application of antibiotics, fecal microbiota transplantation, and oncolytic bacteria has improved tumor treatment outcomes, which provides a novel insight into developing therapeutic strategies for urologic cancer.}, }
@article {pmid38910152, year = {2024}, author = {Byndloss, M and Devkota, S and Duca, F and Niess, JH and Nieuwdorp, M and Orho-Melander, M and Sanz, Y and Tremaroli, V and Zhao, L}, title = {The gut microbiota and diabetes: research, translation, and clinical applications - 2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.}, journal = {Diabetologia}, volume = {67}, number = {9}, pages = {1760-1782}, pmid = {38910152}, issn = {1432-0428}, support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 DK131104/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/microbiology/metabolism ; Translational Research, Biomedical ; }, abstract = {This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.}, }
@article {pmid38908958, year = {2024}, author = {Haddad, A and Holder, AM}, title = {Microbiome and Immunotherapy for Melanoma: Are We Ready for Clinical Application?.}, journal = {Hematology/oncology clinics of North America}, volume = {38}, number = {5}, pages = {1061-1070}, doi = {10.1016/j.hoc.2024.05.010}, pmid = {38908958}, issn = {1558-1977}, support = {R01 CA289456/CA/NCI NIH HHS/United States ; }, mesh = {*Melanoma/therapy/immunology ; Humans ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {The microbiome plays a substantial role in the efficacy of immune checkpoint blockade (ICB) in patients with metastatic melanoma. While the exact gut microbiome composition and the pathways involved in this interaction are not clearly delineated, novel studies and ongoing clinical trials are likely to reveal findings applicable to the clinical setting for the prediction and optimization of response to ICB. Nevertheless, lifestyle modifications, including high fiber diet, avoidance of unnecessary antibiotic prescriptions, and careful use of probiotics may be helpful to optimize the "health" of the gut microbiome and potentially enhance response to ICB in patients with melanoma.}, }
@article {pmid38908733, year = {2024}, author = {Lau, RI and Su, Q and Ching, JYL and Lui, RN and Chan, TT and Wong, MTL and Lau, LHS and Wing, YK and Chan, RNY and Kwok, HYH and Ho, AHY and Tse, YK and Cheung, CP and Li, MKT and Siu, WY and Liu, C and Lu, W and Wang, Y and Chiu, EOL and Cheong, PK and Chan, FKL and Ng, SC}, title = {Fecal Microbiota Transplantation for Sleep Disturbance in Post-acute COVID-19 Syndrome.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {22}, number = {12}, pages = {2487-2496.e6}, doi = {10.1016/j.cgh.2024.06.004}, pmid = {38908733}, issn = {1542-7714}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/complications/therapy ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Post-Acute COVID-19 Syndrome ; Prospective Studies ; SARS-CoV-2 ; Sleep Initiation and Maintenance Disorders/therapy ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Post-acute COVID-19 syndrome (PACS) is associated with sleep disturbance, but treatment options are limited. The etiology of PACS may be secondary to alterations in the gut microbiome. Here, we report the efficacy of fecal microbiota transplantation (FMT) in alleviating post-COVID insomnia symptoms in a nonrandomized, open-label prospective interventional study.<br><br>METHODS: Between September 22, 2022, and May 22, 2023, we recruited 60 PACS patients with insomnia defined as Insomnia Severity Index (ISI) &#x2265;8 and assigned them to the FMT group (FMT at weeks 0, 2, 4, and 8; n = 30) or the control group (n&#xa0;= 30). The primary outcome was clinical remission defined by an ISI of <8 at 12 weeks. Secondary outcomes included changes in the Pittsburgh Sleep Quality Index, Generalized Anxiety Disorder-7 scale, Epworth Sleepiness Scale, Multidimensional Fatigue Inventory, blood cortisol and melatonin, and gut microbiome analysis on metagenomic sequencing.<br><br>RESULTS: At week 12, more patients in the FMT than the control group had insomnia remission (37.9% vs 10.0%; P&#xa0;= .018). The FMT group showed a decrease in ISI score (P < .0001), Pittsburgh Sleep Quality Index (P < .0001), Generalized Anxiety Disorder-7 scale (P&#xa0;= .0019), Epworth Sleepiness Scale (P&#xa0;= .0057), and blood cortisol concentration (P&#xa0;= .035) from baseline to week 12, but there was no significant change in the control group. There was enrichment of bacteria such as Gemmiger formicilis and depletion of microbial pathways producing menaquinol derivatives after FMT. The gut microbiome profile resembled that of the donor in FMT responders but not in nonresponders at week 12. There was no serious adverse event.<br><br>CONCLUSIONS: This pilot study showed that FMT could be effective and safe in alleviating post-COVID insomnia, and further clinical trials are warranted.<br><br>CLINICALTRIALS: gov, Number: NCT05556733.}, }
@article {pmid38908691, year = {2024}, author = {Mu, YY and Qi, WP and Zhang, T and Zhang, JY and Li, M and Mao, SY}, title = {Changes in rumen epithelial morphology and transcriptome, rumen metabolome, and blood biochemical parameters in lactating dairy cows with subacute rumen acidosis following rumen content transplantation.}, journal = {Journal of dairy science}, volume = {107}, number = {10}, pages = {7960-7972}, doi = {10.3168/jds.2024-24694}, pmid = {38908691}, issn = {1525-3198}, mesh = {Animals ; Cattle ; *Rumen/metabolism ; Female ; *Lactation ; *Acidosis/veterinary ; *Transcriptome ; *Metabolome ; *Diet/veterinary ; Animal Feed ; }, abstract = {Interventions targeting the gut microbiota, such as fecal microbiota transplantation, prove effective in repairing the intestinal barrier and facilitating the recovery of its function and metabolism. However, the regulatory mechanisms governing the remodeling of rumen epithelial morphology and function, rumen metabolism, and host metabolism in cows of SARA remain poorly understood. Here, we explored the changes in rumen epithelial morphology and transcriptome, rumen metabolome, and blood biochemical parameters in SARA cows following rumen content transplantation (RCT). The entire experiment consisted of 2 periods: the SARA induction period and the RCT period. During the SARA induction period, 12 ruminally cannulated lactating Holstein cows were randomly allocated into 2 groups, fed either a conventional diet (CON; n = 4; 40% concentrate, DM basis) or a high-grain diet (HG; n = 8; 60% concentrate, DM basis). Following the SARA induction period, the RCT period started. The HG cows were randomly assigned to 2 groups: the donor-recipient (DR) group and the self-recipient (SR) group. Rumen contents were entirely removed from both groups before RCT. For the DR group, cows were administered 70% rumen content from the CON cows, paired based on comparable BW; for the SR group, each cow received 70% self-derived rumen content. The results revealed no significant differences in the thicknesses of the stratum corneum, granulosum, and spinosum or basale layers, as well as the total depth of the epithelium between the SR and DR groups. All these measurements exhibited a decreasing trend and fluctuations over time after the transfer. Notably, these fluctuations tended to stabilize at 13 or 16 d after RCT in the SR group, whereas they tended to stabilize after 8 or 13 d of transfer for the DR group. Transcriptome sequencing revealed that a total of 277 differentially expressed genes (DEG) were identified between the 2 groups. Enrichment analysis showed that the DEG were significantly enriched in 11 Gene Ontology biological processes and 14 Kyoto Encyclopedia of Genes and Genomes pathways. The DEG corresponding to almost any of these 11 biological process terms and 14 pathways showed mixed up- or downregulation following RCT. Metabolomics analysis indicated that a total of 33 differential metabolites were detected between the SR and DR groups, mainly enriched in 5 key metabolic pathways, including plant polysaccharides and starch degradation, lipid metabolism, amino-sugar and nucleotide-sugar metabolism, purine metabolism, and Krebs cycle. Among them, the levels of differential metabolites associated with the degradation of plant polysaccharides and starches, metabolism of amino sugars and nucleotides, and purine metabolism pathways were significantly elevated in the DR cows. The results of blood biochemical parameters showed that the triglyceride concentration of the DR cows was increased than that of the SR cows, comparable to the level observed in the CON cows during the SARA induction period. Generally, our findings indicated that RCT facilitated the recovery of rumen epithelial morphological structure but did not promote its function recovery. Moreover, RCT enhanced rumen plant polysaccharide and starch degradation, amino-sugar and nucleotide-sugar metabolism, as well as purine metabolism. Additionally, it further promoted the recovery of plasma metabolites related to lipid metabolism.}, }
@article {pmid38908615, year = {2024}, author = {Hu, S and Tang, B and Lu, C and Wang, S and Wu, L and Lei, Y and Tang, L and Zhu, H and Wang, D and Yang, S}, title = {Lactobacillus rhamnosus GG ameliorates triptolide-induced liver injury through modulation of the bile acid-FXR axis.}, journal = {Pharmacological research}, volume = {206}, number = {}, pages = {107275}, doi = {10.1016/j.phrs.2024.107275}, pmid = {38908615}, issn = {1096-1186}, mesh = {Animals ; *Diterpenes/pharmacology ; *Phenanthrenes/pharmacology ; *Chemical and Drug Induced Liver Injury/metabolism/prevention &amp; control ; *Lacticaseibacillus rhamnosus ; *Gastrointestinal Microbiome/drug effects ; *Epoxy Compounds/pharmacology ; *Bile Acids and Salts/metabolism ; Male ; *Mice, Inbred C57BL ; Mice ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Liver/drug effects/metabolism/pathology ; Probiotics/therapeutic use/pharmacology ; Fecal Microbiota Transplantation ; Inflammasomes/metabolism ; Signal Transduction/drug effects ; }, abstract = {Triptolide (TP) is the principal bioactive compound of Tripterygium wilfordii with significant anti-tumor, anti-inflammatory and immunosuppressive activities. However, its severe hepatotoxicity greatly limits its clinical use. The underlying mechanism of TP-induced liver damage is still poorly understood. Here, we estimate the role of the gut microbiota in TP hepatotoxicity and investigate the bile acid metabolism mechanisms involved. The results of the antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) experiment demonstrate the involvement of intestinal flora in TP hepatotoxicity. Moreover, TP treatment significantly perturbed gut microbial composition and reduced the relative abundances of Lactobacillus rhamnosus GG (LGG). Supplementation with LGG reversed TP-induced hepatotoxicity by increasing bile salt hydrolase (BSH) activity and reducing the increased conjugated bile acids (BA). LGG supplementation upregulates hepatic FXR expression and inhibits NLRP3 inflammasome activation in TP-treated mice. In summary, this study found that gut microbiota is involved in TP hepatotoxicity. LGG supplementation protects mice against TP-induced liver damage. The underlying mechanism was associated with the gut microbiota-BA-FXR axis. Therefore, LGG holds the potential to prevent and treat TP hepatotoxicity in the clinic.}, }
@article {pmid38908613, year = {2024}, author = {Xu, Q and Gao, J and Zhao, R and Li, H and Cui, H and Yuan, Z and Ren, H and Cao, B and Wei, B}, title = {Akkermansia muciniphila-derived pentadecanoic acid enhances oxaliplatin sensitivity in gastric cancer by modulating glycolysis.}, journal = {Pharmacological research}, volume = {206}, number = {}, pages = {107278}, doi = {10.1016/j.phrs.2024.107278}, pmid = {38908613}, issn = {1096-1186}, mesh = {*Stomach Neoplasms/drug therapy/metabolism ; *Oxaliplatin/pharmacology/therapeutic use ; Animals ; *Akkermansia/drug effects ; *Gastrointestinal Microbiome/drug effects ; Humans ; Cell Line, Tumor ; *Antineoplastic Agents/pharmacology/therapeutic use ; *Glycolysis/drug effects ; Mice ; Male ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Anti-Bacterial Agents/pharmacology/therapeutic use ; }, abstract = {Accumulating evidence has proved the close association between alterations in gut microbiota and resistance to chemotherapeutic drugs. However, the potential roles of gut microbiota in regulating oxaliplatin sensitivity in gastric cancer (GC) have not been investigated before. We first found that antibiotic treatment diminished the therapeutic efficacy of oxaliplatin in a GC mouse model. Importantly, this effect could be transmitted to germ-free mice via fecal microbiota transplantation, indicating a potential role of gut microbiota modulation in oxaliplatin efficacy. Further, metagenomics data showed that Akkermansia muciniphila (A. muciniphila) ranked first among the bacterial species with decreased relative abundances after antibiotic treatment. Metabolically active A. muciniphila promotes oxaliplatin efficacy. As shown by metabolomics analysis, the metabolic pattern of gut microbiota was disrupted with significantly downregulated levels of pentadecanoic acid (PEA), and the use of PEA significantly promoted oxaliplatin efficacy. Mechanistically, FUBP1 positively regulated aerobic glycolysis of GC cells to hinder the therapeutic efficacy of oxaliplatin. A. muciniphila-derived PEA functioned as an inhibitory factor of glycolysis by directly antagonizing the activity of FUBP1, which potentiated GC responses to oxaliplatin. Our research suggested a key role for intestinal A. muciniphila and its metabolite PEA in promoting oxaliplatin efficacy, thus providing a new perspective for probiotic and prebiotic intervention in GC patients during chemotherapy.}, }
@article {pmid38908272, year = {2024}, author = {Deng, Z and Li, L and Jing, Z and Luo, X and Yu, F and Zeng, W and Bi, W and Zou, J}, title = {Association between environmental phthalates exposure and gut microbiota and metabolome in dementia with Lewy bodies.}, journal = {Environment international}, volume = {190}, number = {}, pages = {108806}, doi = {10.1016/j.envint.2024.108806}, pmid = {38908272}, issn = {1873-6750}, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Phthalic Acids/metabolism ; *Metabolome/drug effects ; Mice ; Animals ; Male ; Female ; Aged ; *Lewy Body Disease/metabolism/microbiology ; *Environmental Exposure ; Dysbiosis/chemically induced/microbiology ; Middle Aged ; }, abstract = {BACKGROUND: Emerging evidence has shown the potential involvement of phthalates (PAEs) exposure in the development of dementia with Lewy bodies (DLB). Metabolomics can reflect endogenous metabolites variation in the progress of disease after chemicals exposure. However, little is known about the association between PAEs, gut microbiota and metabolome in DLB.<br><br>OBJECTIVE: We aim to explore the intricate relationship among urinary PAEs metabolites (mPAEs), dysbiosis of gut bacteria, and metabolite profiles in DLB.<br><br>METHODS: A total of 43 DLB patients and 45 normal subjects were included in this study. Liquid chromatography was used to analyze the levels of mPAEs in the urine of the two populations. High-throughput sequencing and liquid chromatography-mass spectrometry were used to analyze gut microbiota and the profile of gut metabolome, respectively. The fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of mPAEs on gut dysbiosis contribute to aggravating cognitive dysfunction in &#x3b1;-synuclein tg DLB/PD mice.<br><br>RESULTS: The DLB patients had higher DEHP metabolites (MEOHP, MEHHP and MEHP), MMP and MnBP, lower MBP and MBzP than the control group and different microbiota. A significantly higher abundance of Ruminococcus gnavus and lower Prevotella copri, Prevotella stercorea and Bifidobacterium were observed in DLB. Higher 3 DEHP metabolites, MMP, MnBP and lower MBP and MBzP were significantly negatively associated with Prevotella copri, Prevotella stercorea and Bifidobacterium. Additionally, using metabolomics, we found that altered bile acids, short-chain fatty acids and amino acids metabolism are linked to these mPAEs. We further found that FMT of fecal microbiota from highest DEHP metabolites donors significantly impaired cognitive function in the germ-free DLB/PD mice.<br><br>CONCLUSION: Our study suggested that PAEs exposure may alter the microbiota-gut-brain axis and providing novel insights into the interactions among environmental perturbations and microbiome-host in pathogenesis of DLB.}, }
@article {pmid38908193, year = {2024}, author = {Li, J and Shi, B and Ren, X and Hu, J and Li, Y and He, S and Zhang, G and Maolan, A and Sun, T and Qi, X and Zhang, X and Luo, Y and Liu, R and Hua, B}, title = {Lung-intestinal axis, Shuangshen granules attenuate lung metastasis by regulating the intestinal microbiota and related metabolites.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {132}, number = {}, pages = {155831}, doi = {10.1016/j.phymed.2024.155831}, pmid = {38908193}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Mice, Inbred C57BL ; *Drugs, Chinese Herbal/pharmacology ; *Lung Neoplasms/drug therapy ; Mice ; *Carcinoma, Lewis Lung/drug therapy ; Tumor-Associated Macrophages/drug effects ; Male ; Fecal Microbiota Transplantation ; Lung/drug effects/pathology ; }, abstract = {BACKGROUND: Based on the proposed lung-intestinal axis, there is a significant correlation between the microbiota and lung metastasis. Targeting the microbial composition is valuable in modulating the host response to cancer therapeutics. As a traditional Chinese medicine (TCM) formula, Shuangshen granules (SSG) are clinically useful in delaying lung metastasis, but its underlying mechanisms remain unknown.<br><br>METHODS: The C57BL/6N mice were chosen to establish the Lewis lung cancer models. The broad-spectrum antibiotics (ABX) group was set up to estimate the effect of microbiota composition on metastasis. The therapeutic effects of different doses of SSG in treating lung metastasis were investigated through histopathology, immunohistochemistry, and Western blot analysis methods. Additionally, the phenotype of tumor-associated macrophages (TAMs) in the lung and blood was evaluated by flow cytometry. The fecal microbiota transplantation (FMT) and negative control (ABX plus high dose SSG group) experiments were also designed to assess intestinal microbiota's role in SSG intervention's outcome in lung metastasis. The 16S rRNA amplicon sequencing and Untargeted metabolomic analysis were used to analyze intestinal microbiota and metabolite changes mediated by SSG in tumor-bearing mice with lung metastasis.<br><br>RESULT: ABX could observably lead to intestinal microbiota dysbiosis and enhance metastasis. SSG showed a significant chemopreventive effect in lung metastasis, reduced metastatic nodules and the expression levels of pre-metastatic niche biomarkers, and enriched the ratio of CD86+F4/80+CD11b+ cells, while FMT delayed metastasis similarly. The analysis of microbiota and metabolites revealed that SSG significantly enriched probiotics in feces, including Akkermansia muciniphila, Lachnoclostridium sp YL32, Limosilactobacillus reuteri, and potential anti-cancer serum metabolites, including Ginsenoside Rb1, Isoquinoline, Betulin and so on. We also investigated the mechanism of SSG protection against lung metastasis and showed that SSG regulated microbiota, improved TAMs polarization, and inhibited the expression of the NF-&#x3ba;B pathway.<br><br>CONCLUSION: The results presented in our article demonstrated that SSG improved TAMs polarization and inhibited the NF-&#x3ba;B pathway by alleviating intestinal microbiota imbalance and metabolic disorders in tumor-bearing mice, resulting in delayed lung metastasis.}, }
@article {pmid38907332, year = {2024}, author = {Zhou, X and Ji, S and Chen, L and Liu, X and Deng, Y and You, Y and Wang, M and He, Q and Peng, B and Yang, Y and Chen, X and Kwan, HY and Zhou, L and Chen, J and Zhao, X}, title = {Gut microbiota dysbiosis in hyperuricaemia promotes renal injury through the activation of NLRP3 inflammasome.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {109}, pmid = {38907332}, issn = {2049-2618}, support = {82305130//National Natural Science Foundation of China/ ; 82274499//National Natural Science Foundation of China/ ; 2022A1515110810//Natural Science Foundation of Guangdong Province, China/ ; 2023A1515012429//Natural Science Foundation of Guangdong Province, China/ ; 81830117//Key Project of National Natural Science Foundation of China/ ; U22A20365//Joint Funds of National Natural Science Foundation of China/ ; ZYYCXTD-C-202001//Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine/ ; }, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; *Inflammasomes/metabolism ; Mice ; Rats ; *Hyperuricemia ; Male ; Disease Models, Animal ; Kidney ; Mice, Knockout ; RNA, Ribosomal, 16S/genetics ; Fecal Microbiota Transplantation ; Urate Oxidase/metabolism ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown.<br><br>RESULTS: A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3[-/-]) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated.<br><br>CONCLUSION: Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract.}, }
@article {pmid38907315, year = {2024}, author = {Brenchley, JM and Serrano-Villar, S}, title = {From dysbiosis to defense: harnessing the gut microbiome in HIV/SIV therapy.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {113}, pmid = {38907315}, issn = {2049-2618}, support = {ICI20/00058//Instituto de Salud Carlos III/ ; }, mesh = {*Gastrointestinal Microbiome ; *Dysbiosis/therapy/microbiology ; Humans ; *HIV Infections/microbiology/therapy/immunology ; *Simian Acquired Immunodeficiency Syndrome/therapy/immunology/microbiology ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Animals ; *Simian Immunodeficiency Virus ; Prebiotics/administration &amp; dosage ; HIV/physiology ; }, abstract = {BACKGROUND: Although the microbiota has been extensively associated with HIV pathogenesis, the majority of studies, particularly those using omics techniques, are largely correlative and serve primarily as a basis for hypothesis generation. Furthermore, most have focused on characterizing the taxonomic composition of the bacterial component, often overlooking other levels of the microbiome. The intricate mechanisms by which the microbiota influences immune responses to HIV are still poorly understood. Interventional studies on gut microbiota provide a powerful tool to test the hypothesis of whether we can harness the microbiota to improve health outcomes in people with HIV.<br><br>RESULTS: Here, we review the multifaceted role of the gut microbiome in HIV/SIV disease progression and its potential as a therapeutic target. We explore the complex interplay between gut microbial dysbiosis and systemic inflammation, highlighting the potential for microbiome-based therapeutics to open new avenues in HIV management. These include exploring the efficacy of probiotics, prebiotics, fecal microbiota transplantation, and targeted dietary modifications. We also address the challenges inherent in this research area, such as the difficulty in inducing long-lasting microbiome alterations and the complexities of study designs, including variations in probiotic strains, donor selection for FMT, antibiotic conditioning regimens, and the hurdles in translating findings into clinical practice. Finally, we speculate on future directions for this rapidly evolving field, emphasizing the need for a more granular understanding of microbiome-immune interactions, the development of personalized microbiome-based therapies, and the application of novel technologies to identify potential therapeutic agents.<br><br>CONCLUSIONS: Our review underscores the importance of the gut microbiome in HIV/SIV disease and its potential as a target for innovative therapeutic strategies.}, }
@article {pmid38905983, year = {2024}, author = {Zhao, C and Chen, G and Huang, Y and Zhang, Y and Li, S and Jiang, Z and Peng, H and Wang, J and Li, D and Hou, R and Peng, C and Wan, X and Cai, H}, title = {Alleviation of fluoride-induced colitis by tea polysaccharides: Insights into the role of Limosilactobacillus vaginalis and butyric acid.}, journal = {Journal of hazardous materials}, volume = {476}, number = {}, pages = {134858}, doi = {10.1016/j.jhazmat.2024.134858}, pmid = {38905983}, issn = {1873-3336}, mesh = {Animals ; *Butyric Acid/metabolism ; *Fluorides/toxicity ; *Gastrointestinal Microbiome/drug effects ; *Colitis/chemically induced/drug therapy/prevention &amp; control ; *Polysaccharides/pharmacology ; Male ; *Tea/chemistry ; Rats, Sprague-Dawley ; Colon/drug effects/metabolism ; Rats ; }, abstract = {Endemic fluorosis has gained increasing attention as a public health concern, and the escalating risk of colitis resulting from excessive fluoride intake calls for effective mitigation strategies. This study aimed to investigate the potential mechanisms underlying the alleviation of fluoride-induced colitis by Tea polysaccharides (TPS). Under conditions of excessive fluoride intake, significant changes were observed in the gut microbiota of rats, leading to aggravated colitis. However, the intervention of TPS exerted a notable alleviating effect on colitis symptoms. Antibiotic intervention and fecal microbiota transplantation (FMT) experiments provided evidence that TPS-mediated relief of fluoride-induced colitis is mediated through its effects on the gut microbiota. Furthermore, TPS supplementation was found to modulate the structure of gut microbiota, enhance the relative abundance of Limosilactobacillus vaginalis in the gut microbiota, and promote the expression of short-chain fatty acid (SCFAs) receptors in colonic tissue. Notably, L. vaginalis played a significant role in alleviating fluoride-induced colitis and facilitating the absorption of butyric acid in the rat colon. Subsequent butyric acid intervention experiments confirmed its remarkable alleviating effect on fluoride-induced colitis. Overall, these findings provide a potential preventive strategy for fluoride-induced colitis by TPS intervention, which is mediated by L. vaginalis and butyric acid.}, }
@article {pmid38904913, year = {2024}, author = {Calabrese, FM and Genchi, VA and Serale, N and Celano, G and Vacca, M and Palma, G and Svelto, M and Gesualdo, L and De Angelis, M and Giorgino, F and Perrini, S}, title = {Gut microbiota and fecal volatilome profile inspection in metabolically healthy and unhealthy obesity phenotypes.}, journal = {Journal of endocrinological investigation}, volume = {47}, number = {12}, pages = {3077-3090}, pmid = {38904913}, issn = {1720-8386}, support = {ARS0101220//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Feces/microbiology/chemistry ; Female ; Male ; Adult ; Middle Aged ; *Phenotype ; *Obesity/microbiology/metabolism ; Metabolome/physiology ; Obesity, Metabolically Benign/metabolism/microbiology/diagnosis ; Case-Control Studies ; }, abstract = {BACKGROUND: People with metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) differ for the presence or absence of cardio-metabolic complications, respectively.<br><br>OBJECTIVE: Based on these differences, we are interested in deepening whether these obesity phenotypes could be linked to changes in microbiota and metabolome profiles. In this respect, the overt role of microbiota taxa composition and relative metabolic profiles is not completely understood. At this aim, biochemical and nutritional parameters, fecal microbiota, metabolome and SCFA compositions were inspected in patients with MHO and MUO under a restrictive diet regimen with a daily intake ranging from 800 to 1200&#xa0;kcal.<br><br>METHODS: Blood, fecal samples and food questionnaires were collected from healthy controls (HC), and an obese cohort composed of both MHO and MUO patients. Most impacting biochemical/anthropometric variables from an a priori sample stratification were detected by applying a robust statistics approach useful in lowering the background noise. Bacterial taxa and volatile metabolites were assessed by qPCR and gas chromatography coupled with mass spectrometry, respectively. A targeted GC-MS analyses on SCFAs was also performed.<br><br>RESULTS: Instructed to follow a controlled and restricted daily calorie intake, MHO and MUO patients showed differences in metabolic, gut microbial and volatilome signatures. Our data revealed higher quantities of specific pro-inflammatory taxa (i.e., Desulfovibrio and Prevotella genera) and lower quantities of Clostridium coccoides group in MUO subset. Higher abundances in alkane, ketone, aldehyde, and indole VOC classes together with a lower amount of butanoic acid marked the faecal MUO metabolome.<br><br>CONCLUSIONS: Compared to MHO, MUO subset symptom picture is featured by specific differences in gut pro-inflammatory taxa and metabolites that could have a role in the progression to metabolically unhealthy status and developing of obesity-related cardiometabolic diseases. The approach is suitable to better explain the crosstalk existing among dysmetabolism-related inflammation, nutrient intake, lifestyle, and gut dysbiosis.}, }
@article {pmid38903987, year = {2024}, author = {Sun, W and Mei, X and Wang, J and Mai, Z and Xu, D}, title = {Zn(II)-curcumin prevents cadmium-aggravated diabetic nephropathy by regulating gut microbiota and zinc homeostasis.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1411230}, pmid = {38903987}, issn = {1663-9812}, abstract = {Background: Diabetic nephropathy (DN) is known as the most common complication of diabetes, resulting from a complex inheritance-environment interaction without effective clinical treatments. Herein, we revealed the protective effects and mechanisms of Zn(II)-curcumin, a curcumin derivative, against streptozotocin-induced DN in rats in the presence or absence of cadmium exposure. Methods: The present study focused on investigating the therapy of Zn(II)-curcumin against cadmium-aggravated DN by regulating gut microbiota, metabolism, inflammation and zinc homeostasis based on pathological changes, TLR4/NF-κB signaling pathway, inductively coupled plasma-mass spectrometry (ICP-MS), 16S rRNA gene sequencing and gas chromatography-mass spectrometer (GC-MS). Results: We found Zn(II)-curcumin significantly mitigated the cadmium-aggravated phenotypes of diabetic nephropathy, as indicated by the remission of renal dysfunction, pathological changes, inflammation and zinc dyshomeostasis in streptozotocin-treated rats exposed to cadmium. Administration of Zn(II)-curcumin significantly alleviated the dysbiosis of gut microbiota and the changes of serum metabolite profiles in rats treated with streptozotocin in combination with cadmium. Notably, fecal microbial transplantation identified the ability of Zn(II)-curcumin to regulate renal function, inflammation and zinc homeostasis was partly dependent on the gut microbiota. Conclusion: These findings revealed that Zn(II)-curcumin alleviated cadmium-aggravated diabetic nephropathy by reshaping the gut microbiota and zinc homeostasis, which provided unique insights into the mechanisms of the treatment and prevention of diabetic nephropathy.}, }
@article {pmid38903943, year = {2024}, author = {Tang, Y and Chen, L and Yang, J and Zhang, S and Jin, J and Wei, Y}, title = {Gut microbes improve prognosis of Klebsiella pneumoniae pulmonary infection through the lung-gut axis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1392376}, pmid = {38903943}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Klebsiella Infections/microbiology/therapy ; *Klebsiella pneumoniae ; Mice ; *Fecal Microbiota Transplantation ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; *Lung/microbiology/pathology ; *Sepsis/microbiology/therapy ; Prognosis ; Disease Models, Animal ; Humans ; Male ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: The gut microbiota plays a vital role in the development of sepsis and in protecting against pneumonia. Previous studies have demonstrated the existence of the gut-lung axis and the interaction between the gut and the lung, which is related to the prognosis of critically ill patients; however, most of these studies focused on chronic lung diseases and influenza virus infections. The purpose of this study was to investigate the effect of faecal microbiota transplantation (FMT) on Klebsiella pneumoniae-related pulmonary infection via the gut-lung axis and to compare the effects of FMT with those of traditional antibiotics to identify new therapeutic strategies.<br><br>METHODS: We divided the mice into six groups: the blank control (PBS), pneumonia-derived sepsis (KP), pneumonia-derived sepsis + antibiotic (KP + PIP), pneumonia-derived sepsis + faecal microbiota transplantation(KP + FMT), antibiotic treatment control (KP+PIP+PBS), and pneumonia-derived sepsis+ antibiotic + faecal microbiota transplantation (KP + PIP + FMT) groups to compare the survival of mice, lung injury, inflammation response, airway barrier function and the intestinal flora, metabolites and drug resistance genes in each group.<br><br>RESULTS: Alterations in specific intestinal flora can occur in the gut of patients with pneumonia-derived sepsis caused by Klebsiella pneumoniae. Compared with those in the faecal microbiota transplantation group, the antibiotic treatment group had lower levels of proinflammatory factors and higher levels of anti-inflammatory factors but less amelioration of lung pathology and improvement of airway epithelial barrier function. Additionally, the increase in opportunistic pathogens and drug resistance-related genes in the gut of mice was accompanied by decreased production of favourable fatty acids such as acetic acid, propionic acid, butyric acid, decanoic acid, and secondary bile acids such as chenodeoxycholic acid 3-sulfate, isodeoxycholic acid, taurodeoxycholic acid, and 3-dehydrocholic acid; the levels of these metabolites were restored by faecal microbiota transplantation. Faecal microbiota transplantation after antibiotic treatment can gradually ameliorate gut microbiota disorder caused by antibiotic treatment and reduce the number of drug resistance genes induced by antibiotics.<br><br>CONCLUSION: In contrast to direct antibiotic treatment, faecal microbiota transplantation improves the prognosis of mice with pneumonia-derived sepsis caused by Klebsiella pneumoniae by improving the structure of the intestinal flora and increasing the level of beneficial metabolites, fatty acids and secondary bile acids, thereby reducing systemic inflammation, repairing the barrier function of alveolar epithelial cells, and alleviating pathological damage to the lungs. The combination of antibiotics with faecal microbiota transplantation significantly alleviates intestinal microbiota disorder, reduces the selection for drug resistance genes caused by antibiotics, and mitigates lung lesions; these effects are superior to those following antibiotic monotherapy.}, }
@article {pmid38903520, year = {2024}, author = {Xie, Y and Liu, F}, title = {The role of the gut microbiota in tumor, immunity, and immunotherapy.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1410928}, pmid = {38903520}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; Animals ; Dysbiosis/immunology ; Neoplasms/immunology/therapy/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/therapeutic use ; Prebiotics/administration &amp; dosage ; }, abstract = {In recent years, with the deepening understanding of the gut microbiota, it has been recognized to play a significant role in the development and progression of diseases. Particularly in gastrointestinal tumors, the gut microbiota influences tumor growth by dysbiosis, release of bacterial toxins, and modulation of host signaling pathways and immune status. Immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment efficacy by enhancing immune cell responses. Current clinical and preclinical studies have demonstrated that the gut microbiota and its metabolites can enhance the effectiveness of immunotherapy. Furthermore, certain gut microbiota can serve as biomarkers for predicting immunotherapy responses. Interventions targeting the gut microbiota for the treatment of gastrointestinal diseases, especially colorectal cancer (CRC), include fecal microbiota transplantation, probiotics, prebiotics, engineered bacteria, and dietary interventions. These approaches not only improve the efficacy of ICIs but also hold promise for enhancing immunotherapy outcomes. In this review, we primarily discuss the role of the gut microbiota and its metabolites in tumors, host immunity, and immunotherapy.}, }
@article {pmid38903498, year = {2024}, author = {Yang, X and Huang, J and Peng, J and Wang, P and Wong, FS and Wang, R and Wang, D and Wen, L}, title = {Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10[+] Breg cells and protect against T1D.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1413177}, pmid = {38903498}, issn = {1664-3224}, support = {P30 DK045735/DK/NIDDK NIH HHS/United States ; R01 DK126809/DK/NIDDK NIH HHS/United States ; R01 DK130318/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Female ; Mice ; B-Lymphocytes/immunology/metabolism ; *B-Lymphocytes, Regulatory/immunology ; *Diabetes Mellitus, Type 1/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Interleukin-10/metabolism ; Mice, Inbred NOD ; Mice, Knockout ; *Toll-Like Receptor 9/deficiency/genetics/metabolism ; }, abstract = {INTRODUCTION: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β cells. Toll-like receptor 9 (TLR9) plays a role in autoimmune diseases, and B cell-specific TLR9 deficiency delays T1D development. Gut microbiota are implicated in T1D, although the relationship is complex. However, the impact of B cell-specific deficiency of TLR9 on intestinal microbiota and the impact of altered intestinal microbiota on the development of T1D are unclear.<br><br>OBJECTIVES: This study investigated how gut microbiota and the intestinal barrier contribute to T1D development in B cell-specific TLR9-deficient NOD mice. Additionally, this study explored the role of microbiota in immune regulation and T1D onset.<br><br>METHODS: The study assessed gut permeability, gene expression related to gut barrier integrity, and gut microbiota composition. Antibiotics depleted gut microbiota, and fecal samples were transferred to germ-free mice. The study also examined IL-10 production, Breg cell differentiation, and their impact on T1D development.<br><br>RESULTS: B cell-specific TLR9-deficient NOD mice exhibited increased gut permeability and downregulated gut barrier-related gene expression. Antibiotics restored gut permeability, suggesting microbiota influence. Altered microbiota were enriched in Lachnospiraceae, known for mucin degradation. Transferring this microbiota to germ-free mice increased gut permeability and promoted IL-10-expressing Breg cells. Rag[-/-] mice transplanted with fecal samples from Tlr9 [fl/fl] Cd19-Cre[+] mice showed delayed diabetes onset, indicating microbiota's impact.<br><br>CONCLUSION: B cell-specific TLR9 deficiency alters gut microbiota, increasing gut permeability and promoting IL-10-expressing Breg cells, which delay T1D. This study uncovers a link between TLR9, gut microbiota, and immune regulation in T1D, with implications for microbiota-targeted T1D therapies.}, }
@article {pmid38900442, year = {2024}, author = {Yazici, C and Priyadarshini, M and Boulay, B and Dai, Y and Layden, BT}, title = {Alterations in microbiome associated with acute pancreatitis.}, journal = {Current opinion in gastroenterology}, volume = {40}, number = {5}, pages = {413-421}, pmid = {38900442}, issn = {1531-7056}, support = {R01 DK134698/DK/NIDDK NIH HHS/United States ; I01 BX003382/BX/BLRD VA/United States ; P30 DK020595/DK/NIDDK NIH HHS/United States ; R01 CA257807/CA/NCI NIH HHS/United States ; R01 DK104927/DK/NIDDK NIH HHS/United States ; U01 DK127378/DK/NIDDK NIH HHS/United States ; U01 DK127384/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Pancreatitis/microbiology ; *Gastrointestinal Microbiome/physiology ; Severity of Illness Index ; Dysbiosis/microbiology/complications/immunology ; Acute Disease ; Fecal Microbiota Transplantation ; }, abstract = {PURPOSE OF REVIEW: This review evaluates the current knowledge of gut microbiome alterations in acute pancreatitis, including those that can increase acute pancreatitis risk or worsen disease severity, and the mechanisms of gut microbiome driven injury in acute pancreatitis.<br><br>RECENT FINDINGS: Recent observational studies in humans showed the association of gut microbiome changes (decreased gut microbiome diversity, alterations in relative abundances of certain species, and association of unique species with functional pathways) with acute pancreatitis risk and severity. Furthermore, in-vivo studies highlighted the role of gut microbiome in the development and severity of acute pancreatitis using FMT models. The gut barrier integrity, immune cell homeostasis, and microbial metabolites appear to play key roles in acute pancreatitis risk and severity.<br><br>SUMMARY: Large human cohort studies that assess gut microbiome profile, its metabolites and impact on acute pancreatitis risk and severity will be crucial for development of innovative prediction, prevention and treatment strategies.}, }
@article {pmid38899956, year = {2024}, author = {Zhan, H and Wan, Y and Sun, Y and Xu, Z and Zhang, F and Yang, K and Zhu, W and Cheung, CP and Tang, W and Ng, EK and Wong, SK and Yeoh, YK and Kl Chan, F and Miao, Y and Zuo, T and Zeng, Z and Ng, SC}, title = {Gut mycobiome alterations in obesity in geographically different regions.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2367297}, pmid = {38899956}, issn = {1949-0984}, mesh = {*Obesity/microbiology ; Humans ; Animals ; *Gastrointestinal Microbiome ; *Fungi/classification/isolation &amp; purification/genetics ; Male ; Mice ; China ; Female ; *Mycobiome ; *Feces/microbiology ; Adult ; Bacteria/classification/isolation &amp; purification/genetics ; Middle Aged ; Mice, Inbred C57BL ; Body Mass Index ; }, abstract = {The gut fungi play important roles in human health and are involved in energy metabolism. This study aimed to examine gut mycobiome composition in obese subjects in two geographically different regions in China and to identify specific gut fungi associated with obesity. A total of 217 subjects from two regions with different urbanization levels [Hong Kong (HK): obese, n = 59; lean, n = 59; Kunming (KM): obese, n = 50; lean, n = 49. Mean body mass index (BMI) for obesity = 33.7] were recruited. We performed deep shotgun metagenomic sequencing on fecal samples to compare gut mycobiome composition and trophic functions in lean and obese subjects across these two regions. The gut mycobiome of obese subjects in both HK and KM were altered compared to those of lean subjects, characterized by a decrease in the relative abundance of Nakaseomyces, Schizosaccharomyces pombe, Candida dubliniensis and an increase in the abundance of Lanchanceathermotolerans, Saccharomyces paradox, Parastagonospora nodorum and Myceliophthorathermophila. Reduced fungal - bacterial and fungal - fungal correlations as well as increased negative fungal-bacterial correlations were observed in the gut of obese subjects. Furthermore, the anti-obesity effect of fungus S. pombe was further validated using a mouse model. Supplementing high-fat diet-induced obese mice with the fungus for 12 weeks led to a significant reduction in body weight gain (p < 0.001), and an improvement in lipid and glucose metabolism compared to mice without intervention. In conclusion, the gut mycobiome composition and functionalities of obese subjects were altered. These data shed light on the potential of utilizing fungus-based therapeutics for the treatment of obesity. S. pombe may serve as a potential fungal probiotic in the prevention of diet-induced obesity and future human trials are needed.}, }
@article {pmid38898924, year = {2024}, author = {Lin, C and Song, D and Wang, S and Chu, Y and Chi, C and Jia, S and Lin, M and He, C and Jiang, C and Gong, F and Chen, Q}, title = {Polygonatum cyrtonema polysaccharides reshape the gut microbiota to ameliorate dextran sodium sulfate-induced ulcerative colitis in mice.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1424328}, pmid = {38898924}, issn = {1663-9812}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized inflammatory imbalance, intestinal epithelial mucosal damage, and dysbiosis of the gut microbiota. Polygonatum cyrtonema polysaccharides (PCPs) can regulate gut microbiota and inflammation. Here, the different doses of PCPs were administered to dextran sodium sulfate-induced UC mice, and the effects of the whole PCPs were compared with those of the fractionated fractions PCP-1 (19.9 kDa) and PCP-2 (71.6 and 4.2 kDa). Additionally, an antibiotic cocktail was administered to UC mice to deplete the gut microbiota, and PCPs were subsequently administered to elucidate the potential role of the gut microbiota in these mice. The results revealed that PCP treatment significantly optimized the lost weight and shortened colon, restored the balance of inflammation, mitigated oxidative stress, and restored intestinal epithelial mucosal damage. And, the PCPs exhibited superior efficacy in ameliorating these symptoms compared with PCP-1 and PCP-2. However, depletion of the gut microbiota diminished the therapeutic effects of PCPs in UC mice. Furthermore, fecal transplantation from PCP-treated UC mice to new UC-afflicted mice produced therapeutic effects similar to PCP treatment. So, PCPs significantly ameliorated the symptoms, inflammation, oxidative stress, and intestinal mucosal damage in UC mice, and gut microbiota partially mediated these effects.}, }
@article {pmid38898418, year = {2024}, author = {Song, J and Dong, H and Wang, T and Yu, H and Yu, J and Ma, S and Song, X and Sun, Q and Xu, Y and Liu, M}, title = {What is the impact of microbiota on dry eye: a literature review of the gut-eye axis.}, journal = {BMC ophthalmology}, volume = {24}, number = {1}, pages = {262}, pmid = {38898418}, issn = {1471-2415}, support = {2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; }, mesh = {*Dry Eye Syndromes/metabolism/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; Tears/metabolism ; }, abstract = {BACKGROUND: Dry eye is a chronic and multifactorial ocular surface disease caused by tear film instability or imbalance in the microenvironment of the ocular surface. It can lead to various discomforts such as inflammation of the ocular surface and visual issues. However, the mechanism of dry eye is not clear, which results in dry eye being only relieved but not cured in clinical practice. Finding multiple environmental pathways for dry eye and exploring the pathogenesis of dry eye have become the focus of research. Studies have found that changes in microbiota may be related to the occurrence and development of dry eye disease.<br><br>METHODS: Entered the keywords "Dry eye", "Microbiota", "Bacteria" through PUBMED, summarised the articles that meet the inclusion criteria and then filtered them while the publication time range of the literature was defined in the past 5 years, with a deadline of 2023.A total of 13 clinical and 1 animal-related research articles were screened out and included in the summary.<br><br>RESULTS: Study found that different components of bacteria can induce ocular immune responses through different receptors present on the ocular surface, thereby leading to an imbalance in the ocular surface microenvironment. Changes in the ocular surface microbiota and gut microbiota were also found when dry eye syndrome occurs, including changes in diversity, an increase in pro-inflammatory bacteria, and a decrease in short-chain fatty acid-related bacterial genera that produce anti-inflammatory effects. Fecal microbiota transplantation or probiotic intervention can alleviate signs of inflammation on the ocular surface of dry eye animal models.<br><br>CONCLUSIONS: By summarizing the changes in the ocular surface and intestinal microbiota when dry eye occurs, it is speculated and concluded that the intestine may affect the occurrence of eye diseases such as dry eye through several pathways and mechanisms, such as the occurrence of abnormal immune responses, microbiota metabolites- intervention of short-chain fatty acids, imbalance of pro-inflammatory and anti-inflammatory factors, and release of neurotransmitters, etc. Analyzing the correlation between the intestinal tract and the eyes from the perspective of microbiota can provide a theoretical basis and a new idea for relieving dry eyes in multiple ways in the future.}, }
@article {pmid38897131, year = {2024}, author = {Ma, F and Zhang, W and Zhou, G and Qi, Y and Mao, HR and Chen, J and Lu, Z and Wu, W and Zou, X and Deng, D and Lv, S and Xiang, N and Wang, X}, title = {Epimedii Folium decoction ameliorates osteoporosis in mice through NLRP3/caspase-1/IL-1β signalling pathway and gut-bone axis.}, journal = {International immunopharmacology}, volume = {137}, number = {}, pages = {112472}, doi = {10.1016/j.intimp.2024.112472}, pmid = {38897131}, issn = {1878-1705}, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Osteoporosis/drug therapy/metabolism ; *Signal Transduction/drug effects ; *Caspase 1/metabolism ; Mice ; Female ; *Interleukin-1beta/metabolism ; *Epimedium ; Disease Models, Animal ; Mice, Inbred C57BL ; Bone and Bones/drug effects/metabolism ; Insulin-Like Growth Factor I/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {AIM OF THE STUDY: This study aimed to determine the effect of Epimedium brevicornu Maxim. (EF) on osteoporosis (OP) and its underlying molecular mechanisms, and to explore the existence of the "Gut-Bone Axis".<br><br>MATERIAL AND METHODS: The impact of EF decoction (EFD) on OP was evaluated using istopathological examination and biochemical assays. Targeted metabolomics was employed to identify key molecules and explore their molecular mechanisms. Alterations in the gut microbiota (GM) were evaluated by 16S rRNA gene sequencing. The role of the GM was clarified using an antibiotic cocktail and faecal microbiota transplantation.<br><br>RESULTS: EFD significantly increased the weight (14.06%), femur length (4.34%), abdominal fat weight (61.14%), uterine weight (69.86%), and insulin-like growth factor 1 (IGF-1) levels (59.48%), while reducing serum type I collagen cross-linked carboxy-terminal peptide (CTX-I) levels (15.02%) in osteoporotic mice. The mechanism of action may involve the regulation of the NLRP3/cleaved caspase-1/IL-1&#x3b2; signalling pathway in improving intestinal tight junction proteins and bone metabolism. Additionally, EFD modulated the abundance of related GM communities, such as Lactobacillus, Coriobacteriaceae, bacteria of family S24-7, Clostridiales, and Prevotella, and increased propionate and butyrate levels. Antibiotic-induced dysbiosis of gut bacteria disrupted OP regulation of bone metabolism, which was restored by the recovery of GM.<br><br>CONCLUSIONS: Our study is the first to demonstrate that EFD works in an OP mouse model by utilising GM and butyric acid. Thus, EF shows promise as a potential remedy for OP in the future.}, }
@article {pmid38896362, year = {2024}, author = {Agrawal, G and Borody, TJ and Aitken, JM}, title = {Mapping Crohn's Disease Pathogenesis with Mycobacterium paratuberculosis: A Hijacking by a Stealth Pathogen.}, journal = {Digestive diseases and sciences}, volume = {69}, number = {7}, pages = {2289-2303}, pmid = {38896362}, issn = {1573-2568}, mesh = {*Crohn Disease/microbiology ; Humans ; *Mycobacterium avium subsp. paratuberculosis/isolation &amp; purification/pathogenicity ; *Paratuberculosis/microbiology/diagnosis ; Animals ; Gastrointestinal Microbiome/physiology ; }, abstract = {Mycobacterium avium ssp. paratuberculosis (MAP) has been implicated in the development of Crohn's disease (CD) for over a century. Similarities have been noted between the (histo)pathological presentation of MAP in ruminants, termed Johne's disease (JD), and appearances in humans with CD. Analyses of disease presentation and pathology suggest a multi-step process occurs that consists of MAP infection, dysbiosis of the gut microbiome, and dietary influences. Each step has a role in the disease development and requires a better understanding to implementing combination therapies, such as antibiotics, vaccination, faecal microbiota transplants (FMT) and dietary plans. To optimise responses, each must be tailored directly to the activity of MAP, otherwise therapies are open to interpretation without microbiological evidence that the organism is present and has been influenced. Microscopy and histopathology enables studies of the mycobacterium in situ and how the associated disease processes manifest in the patient e.g., granulomas, fissuring, etc. The challenge for researchers has been to prove the relationship between MAP and CD with available laboratory tests and methodologies, such as polymerase chain reaction (PCR), MAP-associated DNA sequences and bacteriological culture investigations. These have, so far, been inconclusive in revealing the relationship of MAP in patients with CD. Improved and accurate methods of detection will add to evidence for an infectious aetiology of CD. Specifically, if the bacterial pathogen can be isolated, identified and cultivated, then causal relationships to disease can be confirmed, especially if it is present in human gut tissue. This review discusses how MAP may cause the inflammation seen in CD by relating its known pathogenesis in cattle, and from examples of other mycobacterial infections in humans, and how this would impact upon the difficulties with diagnostic tests for the organism.}, }
@article {pmid38892659, year = {2024}, author = {Ju, X and Jiang, Z and Ma, J and Yang, D}, title = {Changes in Fecal Short-Chain Fatty Acids in IBS Patients and Effects of Different Interventions: A Systematic Review and Meta-Analysis.}, journal = {Nutrients}, volume = {16}, number = {11}, pages = {}, pmid = {38892659}, issn = {2072-6643}, mesh = {*Irritable Bowel Syndrome/diet therapy/therapy ; Humans ; *Feces/chemistry/microbiology ; *Fatty Acids, Volatile/analysis/metabolism ; Fecal Microbiota Transplantation ; Probiotics ; Propionates/metabolism/analysis ; Randomized Controlled Trials as Topic ; Acetates/analysis ; Female ; Gastrointestinal Microbiome ; Biomarkers/analysis ; Male ; Adult ; Case-Control Studies ; }, abstract = {CONTEXT: Short-chain fatty acids (SCFAs) have been reported to be associated with the pathogenesis of irritable bowel syndrome (IBS), but the results are conflicting.<br><br>OBJECTIVE: Here, a systematic review of case-control studies detecting fecal SCFAs in IBS patients compared with healthy controls (HCs) and self-controlled studies or randomized controlled trials (RCTs) investigating fecal SCFA alterations after interventions were identified from several databases.<br><br>DATA SOURCES: A systematic search of databases (PubMed, Web of Science, and Embase) identified 21 studies published before 24 February 2023. Data extractions: Three independent reviewers completed the relevant data extraction.<br><br>DATA ANALYSIS: It was found that the fecal propionate concentration in IBS patients was significantly higher than that in HCs, while the acetate proportion was significantly lower. Low-FODMAP diets significantly reduced the fecal propionate concentration in the IBS patients while fecal microbiota transplantation and probiotic administration did not significantly change the fecal propionate concentration or acetate proportion.<br><br>CONCLUSIONS: The results suggested that the fecal propionate concentration and acetate proportion could be used as biomarkers for IBS diagnosis. A low-FODMAP diet intervention could potentially serve as a treatment for IBS while FMT and probiotic administration need more robust trials.}, }
@article {pmid38892602, year = {2024}, author = {Popov, J and Despot, T and Avelar Rodriguez, D and Khan, I and Mech, E and Khan, M and Bojadzija, M and Pai, N}, title = {Implications of Microbiota and Immune System in Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {Nutrients}, volume = {16}, number = {11}, pages = {}, pmid = {38892602}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Disease Progression ; Fecal Microbiota Transplantation ; Immune System/metabolism ; Probiotics/therapeutic use ; Fatty Liver/microbiology/immunology ; Animals ; Non-alcoholic Fatty Liver Disease/microbiology/immunology/metabolism ; Anti-Bacterial Agents/therapeutic use ; Liver/metabolism ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent type of liver disease worldwide. The exact pathophysiology behind MASLD remains unclear; however, it is thought that a combination of factors or "hits" act as precipitants for disease onset and progression. Abundant evidence supports the roles of diet, genes, metabolic dysregulation, and the intestinal microbiome in influencing the accumulation of lipids in hepatocytes and subsequent progression to inflammation and fibrosis. Currently, there is no cure for MASLD, but lifestyle changes have been the prevailing cornerstones of management. Research is now focusing on the intestinal microbiome as a potential therapeutic target for MASLD, with the spotlight shifting to probiotics, antibiotics, and fecal microbiota transplantation. In this review, we provide an overview of how intestinal microbiota interact with the immune system to contribute to the pathogenesis of MASLD and metabolic dysfunction-associated steatohepatitis (MASH). We also summarize key microbial taxa implicated in the disease and discuss evidence supporting microbial-targeted therapies in its management.}, }
@article {pmid38892281, year = {2024}, author = {Bose, D and Saha, P and Roy, S and Trivedi, A and More, M and Klimas, N and Tuteja, A and Chatterjee, S}, title = {A Double-Humanized Mouse Model for Studying Host Gut Microbiome-Immune Interactions in Gulf War Illness.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38892281}, issn = {1422-0067}, support = {I01 CX001923/CX/CSRD VA/United States ; I01CX0001923//United States Department of Veterans Affairs/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Persian Gulf Syndrome/immunology/microbiology ; Humans ; Mice ; *Disease Models, Animal ; *Cytokines/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Unraveling the multisymptomatic Gulf War Illness (GWI) pathology and finding an effective cure have eluded researchers for decades. The chronic symptom persistence and limitations for studying the etiologies in mouse models that differ significantly from those in humans pose challenges for drug discovery and finding effective therapeutic regimens. The GWI exposome differs significantly in the study cohorts, and the above makes it difficult to recreate a model closely resembling the GWI symptom pathology. We have used a double engraftment strategy for reconstituting a human immune system coupled with human microbiome transfer to create a humanized-mouse model for GWI. Using whole-genome shotgun sequencing and blood immune cytokine enzyme linked immunosorbent assay (ELISA), we show that our double humanized mice treated with Gulf War (GW) chemicals show significantly altered gut microbiomes, similar to those reported in a Veteran cohort of GWI. The results also showed similar cytokine profiles, such as increased levels of IL-1β, IL-6, and TNF R-1, in the double humanized model, as found previously in a human cohort. Further, a novel GWI Veteran fecal microbiota transfer was used to create a second alternative model that closely resembled the microbiome and immune-system-associated pathology of a GWI Veteran. A GWI Veteran microbiota transplant in humanized mice showed a human microbiome reconstitution and a systemic inflammatory pathology, as reflected by increases in interleukins 1β, 6, 8 (IL-1β, IL-6, IL-8), tumor necrosis factor receptor 1 (TNF R-1), and endotoxemia. In conclusion, though preliminary, we report a novel in vivo model with a human microbiome reconstitution and an engrafted human immune phenotype that may help to better understand gut-immune interactions in GWI.}, }
@article {pmid38891979, year = {2024}, author = {Gavriilaki, E and Christoforidi, M and Ouranos, K and Minti, F and Mallouri, D and Varelas, C and Lazaridou, A and Baldoumi, E and Panteliadou, A and Bousiou, Z and Batsis, I and Sakellari, I and Gioula, G}, title = {Alteration of Gut Microbiota Composition and Diversity in Acute and/or Chronic Graft-versus-Host Disease Following Hematopoietic Stem Cell Transplantation: A Prospective Cohort Study.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38891979}, issn = {1422-0067}, mesh = {*Graft vs Host Disease/microbiology/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; Male ; Female ; Middle Aged ; Adult ; Prospective Studies ; Chronic Disease ; Feces/microbiology ; Transplantation, Homologous/adverse effects ; Acute Disease ; Young Adult ; Aged ; Bacteria/classification/isolation &amp; purification/genetics ; Bronchiolitis Obliterans Syndrome ; }, abstract = {Changes in gut microbiome composition have been implicated in the pathogenesis of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our objective was to explore the microbial abundance in patients with GvHD after allo-HSCT. We conducted a single-center, prospective study in patients who underwent allo-HSCT and developed grade II or higher acute GvHD and/or moderate or severe chronic GvHD, to explore the microbial abundance of taxa at the phylum, family, genus, and species level, and we utilized alpha and beta diversity indices to further describe our findings. We collected fecal specimens at -2 to +2 (T1), +11 to +17 (T2), +25 to +30 (T3), +90 (T4), and +180 (T5) days to assess changes in gut microbiota, with day 0 being the day of allo-HSCT. We included 20 allo-HSCT recipients in the study. Compared with timepoint T1, at timepoint T4 we found a significant decrease in the abundance of Proteobacteria phylum (14.22% at T1 vs. 4.07% at T4, p = 0.01) and Enterobacteriaceae family (13.3% at T1 vs. <0.05% at T4, p < 0.05), as well as a significant increase in Enterococcus species (0.1% at T1 vs. 12.8% at T4, p < 0.05) in patients who developed acute GvHD. Regarding patients who developed chronic GvHD after allo-HSCT, there was a significant reduction in the abundance of Eurobactereaceae family (1.32% at T1 vs. 0.53% at T4, p < 0.05) and Roseruria genus (3.97% at T1 vs. 0.09% at T4, p < 0.05) at T4 compared with T1. Alpha and beta diversity analyses did not reveal a difference in the abundance of bacteria at the genus level in GvHD patients at T4 compared with T1. Our study reinforces results from previous studies regarding changes in gut microbiota in patients with acute GvHD and provides new data regarding the gut microbiome changes in chronic GvHD. Future studies will need to incorporate clinical parameters in their analyses to establish their association with specific changes in gut microbiota in patients with GvHD after allo-HSCT.}, }
@article {pmid38891970, year = {2024}, author = {Averina, OV and Poluektova, EU and Zorkina, YA and Kovtun, AS and Danilenko, VN}, title = {Human Gut Microbiota for Diagnosis and Treatment of Depression.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38891970}, issn = {1422-0067}, support = {20-14-00132//Russian Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Depression/therapy/microbiology/diagnosis ; *Probiotics/therapeutic use ; Biomarkers ; Fecal Microbiota Transplantation ; Brain-Gut Axis ; Prebiotics/administration &amp; dosage ; }, abstract = {Nowadays, depressive disorder is spreading rapidly all over the world. Therefore, attention to the studies of the pathogenesis of the disease in order to find novel ways of early diagnosis and treatment is increasing among the scientific and medical communities. Special attention is drawn to a biomarker and therapeutic strategy through the microbiota-gut-brain axis. It is known that the symbiotic interactions between the gut microbes and the host can affect mental health. The review analyzes the mechanisms and ways of action of the gut microbiota on the pathophysiology of depression. The possibility of using knowledge about the taxonomic composition and metabolic profile of the microbiota of patients with depression to select gene compositions (metagenomic signature) as biomarkers of the disease is evaluated. The use of in silico technologies (machine learning) for the diagnosis of depression based on the biomarkers of the gut microbiota is given. Alternative approaches to the treatment of depression are being considered by balancing the microbial composition through dietary modifications and the use of additives, namely probiotics, postbiotics (including vesicles) and prebiotics as psychobiotics, and fecal transplantation. The bacterium Faecalibacterium prausnitzii is under consideration as a promising new-generation probiotic and auxiliary diagnostic biomarker of depression. The analysis conducted in this review may be useful for clinical practice and pharmacology.}, }
@article {pmid38889450, year = {2024}, author = {Zhang, H and Li, C and Han, L and Xiao, Y and Bian, J and Liu, C and Gong, L and Liu, Z and Wang, M}, title = {MUP1 mediates urolithin A alleviation of chronic alcohol-related liver disease via gut-microbiota-liver axis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2367342}, pmid = {38889450}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; Mice ; *Liver/metabolism/drug effects ; *Liver Diseases, Alcoholic/microbiology/metabolism/prevention &amp; control ; Male ; *Endoplasmic Reticulum Stress/drug effects ; *Mice, Inbred C57BL ; *Coumarins/pharmacology/metabolism ; Dysbiosis/microbiology ; Humans ; Bacteria/metabolism/classification/genetics/isolation &amp; purification ; }, abstract = {Alcohol-related liver disease (ALD) is recognized as a global health crisis, contributing to approximately 20% of liver cancer-associated fatalities. Dysbiosis of the gut microbiome is associated with the development of ALD, with the gut microbial metabolite urolithin A (UA) exhibiting a potential for alleviating liver symptoms. However, the protective efficacy of UA against ALD and its underlying mechanism mediated by microbiota remain elusive. In this study, we provide evidence demonstrating that UA effectively ameliorates alcohol-induced metabolic disorders and hepatic endoplasmic reticulum (ER) stress through a specific gut-microbiota-liver axis mediated by major urinary protein 1 (MUP1). Moreover, UA exhibited the potential to restore alcohol-induced dysbiosis of the intestinal microbiota by enriching the abundance of Bacteroides sartorii (B. sartorii), Parabacteroides distasonis (P. distasonis), and Akkermansia muciniphila (A. muciniphila), along with their derived metabolite propionic acid. Partial attenuation of the hepatoprotective effects exerted by UA was observed upon depletion of gut microbiota using antibiotics. Subsequently, a fecal microbiota transplantation (FMT) experiment was conducted to evaluate the microbiota-dependent effects of UA in ALD. FMT derived from mice treated with UA exhibited comparable efficacy to direct UA treatment, as it effectively attenuated ER stress through modulation of MUP1. It was noteworthy that strong associations were observed among the hepatic MUP1, gut microbiome, and metabolome profiles affected by UA. Intriguingly, oral administration of UA-enriched B. sartorii, P. distasonis, and A. muciniphila can enhance propionic acid production to effectively suppress ER stress via MUP1, mimicking UA treatment. Collectively, these findings elucidate the causal mechanism that UA alleviated ALD through the gut-microbiota-liver axis. This unique mechanism sheds light on developing novel microbiome-targeted therapeutic strategies against ALD.}, }
@article {pmid38886569, year = {2024}, author = {Lin, G and Zhang, F and Weng, X and Hong, Z and Ye, D and Wang, G}, title = {Role of gut microbiota in the pathogenesis of castration-resistant prostate cancer: a comprehensive study using sequencing and animal models.}, journal = {Oncogene}, volume = {43}, number = {31}, pages = {2373-2388}, pmid = {38886569}, issn = {1476-5594}, mesh = {Male ; Animals ; *Gastrointestinal Microbiome ; Mice ; *Prostatic Neoplasms, Castration-Resistant/microbiology/pathology/genetics/metabolism ; Humans ; *Toll-Like Receptor 4/metabolism/genetics ; *Myeloid Differentiation Factor 88/metabolism/genetics ; Signal Transduction ; NF-kappa B/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Cell Proliferation ; RNA, Ribosomal, 16S/genetics ; Tumor Necrosis Factor-alpha/metabolism/genetics ; Cell Line, Tumor ; Dysbiosis/microbiology ; }, abstract = {CRPC remains a significant challenge in prostate cancer research. We aimed to elucidate the role of gut microbiota and its specific mechanisms in CRPC using a multidisciplinary approach. We analyzed 16S rRNA sequencing data from mouse fecal samples, revealing substantial differences in gut microbiota composition between CRPC and castration-sensitive prostate cancer mice, particularly in Firmicutes and Bacteroidetes. Functional analysis suggested different bacteria may influence CRPC via the α-linolenic acid metabolism pathway. In vivo, experiments utilizing mouse models and fecal microbiota transplantation (FMT) demonstrated that FMT from healthy control mice could decelerate tumor growth in CRPC mice, reduce TNF-α levels, and inhibit the activation of the TLR4/MyD88/NF-κB signaling pathway. Transcriptome sequencing identified crucial genes and pathways, with rescue experiments confirming the gut microbiota's role in modulating CRPC progression through the TLR4/MyD88/NF-κB pathway. The activation of this pathway by TNF-α has been corroborated by in vitro cell experiments, indicating its role in promoting prostate cancer cell proliferation, migration, and invasion while inhibiting apoptosis. Gut microbiota dysbiosis may promote CRPC development through TNF-α activation of the TLR4/MyD88/NF-κB signaling pathway, potentially linked to α-linolenic acid metabolism.}, }
@article {pmid38885604, year = {2024}, author = {Balasundaram, D and Veerasamy, V and Sylvia Singarayar, M and Neethirajan, V and Ananth Devanesan, A and Thilagar, S}, title = {Therapeutic potential of probiotics in gut microbial homeostasis and Rheumatoid arthritis.}, journal = {International immunopharmacology}, volume = {137}, number = {}, pages = {112501}, doi = {10.1016/j.intimp.2024.112501}, pmid = {38885604}, issn = {1878-1705}, mesh = {Humans ; *Arthritis, Rheumatoid/therapy/immunology/microbiology/drug therapy ; *Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Animals ; *Dysbiosis/therapy ; *Homeostasis ; Fecal Microbiota Transplantation ; }, abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint damage. Existing treatment options primarily focus on managing symptoms and slowing disease progression, often with side effects and limitations. The gut microbiome, a vast community of microorganisms present in the gastrointestinal tract, plays a crucial role in health and disease. Recent research suggests a bidirectional relationship between the gut microbiome and RA, highlighting its potential as a therapeutic option. This review focuses on the interaction between the gut microbiome and RA development, by discussing how dysbiosis, an imbalance in gut bacteria, can contribute to RA through multiple mechanisms such as molecular mimicry, leaky gut, and metabolic dysregulation. Probiotics, live microorganisms with health benefits, are emerging as promising tools for managing RA. They can prevent the negative effects of dysbiosis by displacing harmful bacteria, producing anti-inflammatory metabolites like short-chain fatty acids (SCFA), Directly influencing immune cells, and modifying host metabolism. animal and clinical studies demonstrate the potential of probiotics in improving RA symptoms and disease outcomes. However, further research is needed to optimize probiotic strains, dosages, and treatment protocols for personalized and effective management of RA. This review summarizes the current understanding of the gut microbiome and its role in RA and discusses future research directions. In addition to the established role of gut dysbiosis in RA, emerging strategies like fecal microbiota transplantation, prebiotics, and postbiotics offer exciting possibilities. However, individual variations in gut composition necessitate personalized treatment plans. Long-term effects and clear regulations need to be established. Future research focusing on metagenomic analysis, combination therapies, and mechanistic understanding will unlock the full potential of gut microbiome modulation for effective RA management.}, }
@article {pmid38885258, year = {2024}, author = {Ma, X and Shin, YJ and Yun, SW and Jang, SW and Han, SW and Kim, DH}, title = {Probiotic LB101 alleviates dry eye in mice by suppressing matrix metalloproteinase-9 expression through the regulation of gut microbiota-involved NF-κB signaling.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0303423}, pmid = {38885258}, issn = {1932-6203}, mesh = {Animals ; *Matrix Metalloproteinase 9/metabolism ; *Dry Eye Syndromes/metabolism/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Mice ; *NF-kappa B/metabolism ; *Probiotics/pharmacology/administration &amp; dosage ; *Signal Transduction/drug effects ; Mice, Inbred C57BL ; Tears/metabolism ; Fecal Microbiota Transplantation ; Tumor Necrosis Factor-alpha/metabolism ; Conjunctiva/metabolism/microbiology/pathology ; }, abstract = {Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-α, IL-1β, and MMP-9 expression and TNF-α+ and NF-κB+CD11c+ cell populations in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed Muribaculaceae, Prevotellaceae, and Lactobacillaceae populations in the gut microbiota, while eFMT-induced Bacteroidaceae population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-α and IL-1β with the regulation of gut microbiota-involved NF-κB signaling.}, }
@article {pmid38879538, year = {2024}, author = {Hu, L and Sun, L and Yang, C and Zhang, DW and Wei, YY and Yang, MM and Wu, HM and Fei, GH}, title = {Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {570}, pmid = {38879538}, issn = {1479-5876}, support = {82170050//National Natural Science Foundation of China/ ; 202304295107020038//Anhui Province clinical medical research transformation project/ ; 2023AH010082//Anhui university excellent research and innovation team plan/ ; 2020xkjT061//Anhui Medical University scientific research platform base construction promotion plan/ ; }, mesh = {Animals ; *Tight Junctions/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Acetates/metabolism ; Humans ; *Lung Injury ; *Orthomyxoviridae Infections/complications ; Mice, Inbred C57BL ; Influenza A virus ; Fecal Microbiota Transplantation ; Receptors, G-Protein-Coupled/metabolism ; Mice ; Epithelial Cells/metabolism ; Dysbiosis ; Fatty Acids, Volatile/metabolism ; }, abstract = {BACKGROUND: Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown.<br><br>METHODS: A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA).<br><br>RESULTS: IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-&#x3b1;, IL-6, and IL-1&#x3b2;). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner.<br><br>CONCLUSION: Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.}, }
@article {pmid38879003, year = {2024}, author = {Wu, J and Chen, X and Qian, J and Li, G}, title = {Clinical improvement effect of regulating gut microbiota on metabolic dysfunction-associated steatotic liver disease: Systematic review and meta-analysis of randomized controlled trials.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {48}, number = {7}, pages = {102397}, doi = {10.1016/j.clinre.2024.102397}, pmid = {38879003}, issn = {2210-741X}, mesh = {Humans ; Anti-Bacterial Agents/administration &amp; dosage ; *Fatty Liver/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; *Prebiotics/administration &amp; dosage ; *Probiotics/administration &amp; dosage ; Randomized Controlled Trials as Topic ; *Synbiotics/administration &amp; dosage ; }, abstract = {BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is constantly rising globally. There are barely any effective medications or supplements for the management of MASLD. We aim to systematically evaluate the most current evidence for gut microbiota-regulating supplements in patients with MASLD.<br><br>METHODS: We searched multiple electronic data for randomized controlled trials (RCTs) published from January 1, 2012, to July 15, 2023. The intervention measures included probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The control group was treated with a placebo or usual care. The intervention duration was divided into two periods (>12 weeks and &#x2264;12 weeks). Adequate evaluation data for antibiotics and FMT have not been obtained. Therefore, the other three microbiota regulators are the primary evaluation measures in this study.<br><br>RESULTS: We found that probiotics alone could not improve clinical indicators in MASLD patients. However, synbiotics exhibited an improvement in reducing liver steatosis, TNF-&#x251; levels, and increasing HDL-c levels, and the inflammatory markers of liver cells (ALT and AST) were also improved. For the effective intervention duration, this systematic review suggested that around 12 weeks is an ideal intervention cycle for MASLD patients.<br><br>CONCLUSIONS: This meta-analysis supported the modulation of gut microbiota with synbiotics in the management of MASLD.}, }
@article {pmid38878554, year = {2024}, author = {Mincic, AM and Antal, M and Filip, L and Miere, D}, title = {Modulation of gut microbiome in the treatment of neurodegenerative diseases: A systematic review.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {7}, pages = {1832-1849}, doi = {10.1016/j.clnu.2024.05.036}, pmid = {38878554}, issn = {1532-1983}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/microbiology/therapy ; *Probiotics/administration &amp; dosage/therapeutic use ; *Prebiotics/administration &amp; dosage ; *Dysbiosis/therapy/microbiology ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND AND AIMS: Microbiota plays an essential role in maintaining body health, through positive influences on metabolic, defensive, and trophic processes and on intercellular communication. Imbalance in intestinal flora, with the proliferation of harmful bacterial species (dysbiosis) is consistently reported in chronic illnesses, including neurodegenerative diseases (ND). Correcting dysbiosis can have a beneficial impact on the symptoms and evolution of ND. This review examines the effects of microbiota modulation through administration of probiotics, prebiotics, symbiotics, or prebiotics' metabolites (postbiotics) in patients with ND like multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).<br><br>METHODS: PubMed, Web of Science, Medline databases and ClinicalTrials.gov registry searches were performed using pre-/pro-/postbiotics and ND-related terms. Further references were obtained by checking relevant articles.<br><br>RESULTS: Although few compared to animal studies, the human studies generally show positive effects on disease-specific symptoms, overall health, metabolic parameters, on oxidative stress and immunological markers. Therapy with probiotics in various forms (mixtures of bacterial strains, fecal microbiota transplant, diets rich in fermented foods) exert favorable effects on patients' mental health, cognition, and quality of life, targeting pathogenetic ND mechanisms and inducing reparatory mechanisms at the cellular level. More encouraging results have been observed in prebiotic/postbiotic therapy in some ND.<br><br>CONCLUSIONS: The effects of probiotic-related interventions depend on the patients' ND stage and pre-existing allopathic medication. Further studies on larger cohorts and long term comprehensive neuropsychiatric, metabolic, biochemical testing, and neuroimaging monitoring are necessary to optimize therapeutic protocols in ND.}, }
@article {pmid38878524, year = {2024}, author = {Jia, R and Shao, S and Zhang, P and Yuan, Y and Rong, W and An, Z and Lv, S and Feng, Y and Liu, N and Feng, Q and Wang, Y and Li, Q}, title = {PRM1201 effectively inhibits colorectal cancer metastasis via shaping gut microbiota and short- chain fatty acids.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {132}, number = {}, pages = {155795}, doi = {10.1016/j.phymed.2024.155795}, pmid = {38878524}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Colorectal Neoplasms/drug therapy/pathology ; *Fatty Acids, Volatile/metabolism/pharmacology ; Animals ; Humans ; Mice ; Male ; Female ; Neoplasm Metastasis ; Mice, Inbred BALB C ; Feces/microbiology ; Middle Aged ; Tandem Mass Spectrometry ; Epithelial-Mesenchymal Transition/drug effects ; }, abstract = {BACKGROUND: PRM1201 is a traditional medicine with beneficial effects against colorectal cancer (CRC) metastasis. However, the underlying mechanism of this action remains to be determined.<br><br>HYPOTHESIS: Remodeling microbiota and short-chain fatty acids (SCFAs) metabolism might be a potential mechanism to explain the anti-metastatic action of PRM1201, as this gut-microbiota dependent effect involves downregulation of histone deacetylation and EMT.<br><br>METHODS: To investigate this possibility, clinical specimens were sequenced and the correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFA-producing bacteria was studied. To obtain solid causal evidence, a mouse metastasis model was established to detect the influence of PRM1201 on cancer metastasis. Specifically, 16S amplicon sequencing, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, and bacterial manipulation were used to examine the gut microbiota-driven anti-metastatic action of PRM1201.<br><br>RESULTS: Clinical data showed that PRM1201 increased both the number of SCFA-producing bacteria and generation of SCFAs in the feces of CRC patients. A positive correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFAs observed. The animal experiments demonstrated that PRM1201 effectively blocked CRC metastasis in a dose-dependent manner. PRM1201 treatment modulated the composition of gut microbiota, and promoted the proliferation of beneficial SCFAs producers such as Akkermansia, Lachnospiraceae_NK4A136_group and Blautia, while simultaneously reducing the abundance of pathogenic bacteria like Escherichia-Shigella. In addition, PRM1201 led to augmentation of SCFAs content. Further results indicated that the anti-cancer metastatic mechanism of PRM1201 was linked to inhibition of histone deacetylation and suppression of epithelial-to-mesenchymal transition (EMT) in metastatic lesions. Microbiota depletion treatment and fecal microbiota transplantation (FMT) underscored the microbiota-dependent nature of this phenomenon. Moreover, this anti-colorectal cancer metastatic effect and mechanism of total SCFAs and single SCFA were also confirmed.<br><br>CONCLUSION: In summary, PRM1201 exerts its anti-metastatic effects by modulating SCFA-producing bacteria and enhancing the production of SCFAs. Furthermore, the prebiotic-like actions of PRM1201, along with the PRM1201-treated bacteria, function as inhibitors of histone deacetylases (DHACs) thereby effectively suppressing EMT events.}, }
@article {pmid38878076, year = {2024}, author = {Jawanda, IK and Soni, T and Kumari, S and Prabha, V}, title = {The evolving facets of vaginal microbiota transplantation: reinvigorating the unexplored frontier amid complex challenges.}, journal = {Archives of microbiology}, volume = {206}, number = {7}, pages = {306}, pmid = {38878076}, issn = {1432-072X}, mesh = {Animals ; Female ; Humans ; Anti-Bacterial Agents/therapeutic use ; *Dysbiosis/microbiology/therapy ; Lactobacillus ; *Microbiota ; *Probiotics/administration &amp; dosage ; *Vagina/microbiology ; }, abstract = {In an age of cutting-edge sequencing methods and worldwide endeavors such as The Human Microbiome Project and MetaHIT, the human microbiome stands as a complex and diverse community of microorganisms. A central theme in current scientific inquiry revolves around reinstating a balanced microbial composition, referred to as "eubiosis," as a targeted approach for treating vast array of diseases. Vaginal Microbiota Transplantation (VMT), inspired by the success of fecal microbiota transplantation, emerges as an innovative therapy addressing vaginal dysbacteriosis by transferring the complete microbiota from a healthy donor. Antibiotics, while effective, pose challenges with adverse effects, high recurrence rates, and potential harm to beneficial Lactobacillus strains. Continued antibiotic usage also sparks worries regarding the development of resistant strains. Probiotics, though showing promise, exhibit inconsistency in treating multifactorial diseases, and concerns linger about their suitability for diverse genetic backgrounds. Given the recurrent challenges associated with antibiotic and probiotic treatments, VMT emerges as an imperative alternative, offering a unique and promising avenue for efficiently and reliably managing vaginal dysbiosis among a majority of women. This review critically evaluates findings from both animal and human studies, offering nuanced insights into the efficacy and challenges of VMT. An extensive analysis of clinical trials, provides a current overview of ongoing and completed trials, shedding light on the evolving clinical landscape and therapeutic potential of VMT. Delving into the origins, mechanisms, and optimized protocols of VMT, the review underscores the imperative for sustained research efforts to advance this groundbreaking gynecological therapy.}, }
@article {pmid38877311, year = {2024}, author = {Mu, YF and Gao, ZX and Mao, ZH and Pan, SK and Liu, DW and Liu, ZS and Wu, P}, title = {Perspectives on the involvement of the gut microbiota in salt-sensitive hypertension.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {47}, number = {9}, pages = {2351-2362}, pmid = {38877311}, issn = {1348-4214}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Hypertension/microbiology/physiopathology ; *Sodium Chloride, Dietary/adverse effects ; Animals ; Fatty Acids, Volatile/metabolism ; }, abstract = {Salt-sensitivity hypertension (SSH) is an independent predictor of cardiovascular event-related death. Despite the extensiveness of research on hypertension, which covers areas such as the sympathetic nervous system, the renin-angiotensin system, the vascular system, and the immune system, its pathogenesis remains elusive, with sub-optimal blood pressure control in patients. The gut microbiota is an important component of nutritional support and constitutes a barrier in the host. Long-term high salt intake can lead to gut microbiota dysbiosis and cause significant changes in the expression of gut microbiota-related metabolites. Of these metabolites, short chain fatty acids (SCFAs), trimethylamine oxide, amino acids, bile acids, and lipopolysaccharide are essential mediators of microbe-host crosstalk. These metabolites may contribute to the incidence and development of SSH via inflammatory, immune, vascular, and nervous pathways, among others. In addition, recent studies, including those on the histone deacetylase inhibitory mechanism of SCFAs and the blood pressure-decreasing effects of H2S via vascular activation, suggest that several proteins and factors in the classical pathway elicit their effects through multiple non-classical pathways. This review summarizes changes in the gut microbiota and its related metabolites in high-salt environments, as well as corresponding treatment methods for SSH, such as diet management, probiotic and prebiotic use, antibiotic use, and fecal transplantation, to provide new insights and perspectives for understanding SSH pathogenesis and the development of strategies for its treatment.}, }
@article {pmid38874788, year = {2024}, author = {Hazra, R and Chattopadhyay, S and Mallick, A and Gayen, S and Roy, S}, title = {Revealing the therapeutic properties of gut microbiota: transforming cancer immunotherapy from basic to clinical approaches.}, journal = {Medical oncology (Northwood, London, England)}, volume = {41}, number = {7}, pages = {175}, pmid = {38874788}, issn = {1559-131X}, mesh = {*Gastrointestinal Microbiome/immunology ; Humans ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology ; Fecal Microbiota Transplantation/methods ; Immune Checkpoint Inhibitors/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {The immune system plays a pivotal role in the battle against cancer, serving as a formidable guardian in the ongoing fight against malignant cells. To combat these malignant cells, immunotherapy has emerged as a prevalent approach leveraging antibodies and peptides such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 to inhibit immune checkpoints and activate T lymphocytes. The optimization of gut microbiota plays a significant role in modulating the defense system in the body. This study explores the potential of certain gut-resident bacteria to amplify the impact of immunotherapy. Contemporary antibiotic treatments, which can impair gut flora, may diminish the efficacy of immune checkpoint blockers. Conversely, probiotics or fecal microbiota transplantation can help re-establish intestinal microflora equilibrium. Additionally, the gut microbiome has been implicated in various strategies to counteract immune resistance, thereby enhancing the success of cancer immunotherapy. This paper also acknowledges cutting-edge technologies such as nanotechnology, CAR-T therapy, ACT therapy, and oncolytic viruses in modulating gut microbiota. Thus, an exhaustive review of literature was performed to uncover the elusive link that could potentiate the gut microbiome's role in augmenting the success of cancer immunotherapy.}, }
@article {pmid38874578, year = {2024}, author = {Liu, H and Yan, C and Teng, Y and Guo, J and Liang, C and Xia, X}, title = {Gut microbiota and D-ribose mediate the anti-colitic effect of punicalagin in DSS-treated mice.}, journal = {Food &amp; function}, volume = {15}, number = {13}, pages = {7108-7123}, doi = {10.1039/d4fo00741g}, pmid = {38874578}, issn = {2042-650X}, mesh = {Animals ; *Hydrolyzable Tannins/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Dextran Sulfate ; *Colitis/chemically induced/drug therapy/microbiology ; *Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; }, abstract = {Background: Inflammatory bowel disease (IBD) is an increasing health burden worldwide. Punicalagin, a bioactive component rich in pomegranate rind, has been shown to attenuate chemical or bacteria-induced experimental colitis in mice, but whether punicalagin exerts its function through modulating gut microbiota and metabolites remains unexplored. Results: Punicalagin (100 mg per kg per day) administered orally to mice alleviated dextran-sodium sulfate (DSS)-induced colitis. Gut microbiota analyzed by 16S rRNA sequencing showed that punicalagin altered gut microbiota by increasing the Lachnospiraceae_NK4A136_group and Bifidobacterium abundance. To evaluate the effect of punicalagin-modulated microbiota and its metabolites in colitis mice, we transplanted fecal microbiota and sterile fecal filtrate (SFF) to mice treated with oral antibiotics. The results of fecal microbiota transplantation (FMT) demonstrated that punicalagin's anti-colitic effect is transferable by transplanting punicalagin-modulated gut microbiota and its metabolites. Additionally, we discovered that punicalagin-modulated sterile fecal filtrate also exhibits anti-colitis effects, as evidenced by improved intestinal barrier integrity and decreased inflammation. Subsequently, fecal metabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). The analysis revealed that punicalagin significantly increased the level of D-ribose. In vitro experiments showed that D-ribose has both anti-inflammatory and antioxidant properties. Furthermore, D-ribose significantly mitigated DSS-induced colitis symptoms in mice. Conclusions: Overall, this study demonstrated that gut microbiota and its metabolites partly mediate the protective effect of punicalagin against DSS-induced colitis in mice. D-ribose is a key metabolite that contributes to the anti-colitic effect of punicalagin in mice.}, }
@article {pmid38874442, year = {2024}, author = {Bulnes, R and Utay, NS}, title = {Therapeutic microbiome modulation: new frontiers in HIV treatment.}, journal = {Current opinion in HIV and AIDS}, volume = {19}, number = {5}, pages = {268-275}, doi = {10.1097/COH.0000000000000864}, pmid = {38874442}, issn = {1746-6318}, mesh = {Humans ; *HIV Infections/complications/microbiology/immunology/therapy ; *Dysbiosis/therapy ; *Gastrointestinal Microbiome ; Probiotics/administration &amp; dosage/therapeutic use ; Fecal Microbiota Transplantation/methods ; Prebiotics/administration &amp; dosage ; Microbiota ; Inflammation/immunology/therapy ; }, abstract = {PURPOSE OF REVIEW: Dysbiosis may be a key driver of systemic inflammation, which increases the risk of non-AIDS events in people living with HIV (PLWH). Modulation of the microbiome to reverse this dysbiosis may be a novel approach to decrease inflammation and therefore morbidity and mortality in PLWH.<br><br>RECENT FINDINGS: Fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, postbiotics, and dietary modifications have the potential to modulate the microbiome. These interventions have been well tolerated in clinical trials to date. However, these interventions have not resulted in consistent or lasting changes to the microbiome or consistent changes in biomarkers of intestinal permeability, microbial translocation, inflammation, immune activation, or CD4 + T cell counts. Sustained engraftment may require prebiotics and/or dietary modifications added to either probiotics or FMT.<br><br>SUMMARY: Adequately powered randomized controlled trials are needed to elucidate whether microbiome modulation can be achieved and impact systemic inflammation in PLWH.}, }
@article {pmid38873648, year = {2024}, author = {Levy, B and Fliss Isakov, N and Ziv-Baran, T and Leshno, M and Maharshak, N and Werner, L}, title = {Economic and Chronologic Optimization of Fecal Donors Screening Process.}, journal = {MDM policy &amp; practice}, volume = {9}, number = {1}, pages = {23814683241254809}, pmid = {38873648}, issn = {2381-4683}, abstract = {UNLABELLED: Background. Fecal microbial transplantation (FMT) is the delivery of fecal microbiome, isolated from healthy donors, into a patient's gastrointestinal tract. FMT is a safe and efficient treatment for recurrent Clostridioides difficile infection. Donors undergo strict screening to avoid disease transmission. This consists of several blood and stool tests, which are performed in a multistage, costly process. We performed a cost-minimizing analysis to find the optimal order in which the tests should be performed. Methods. An algorithm to optimize the order of tests in terms of cost was defined. Performance analysis for disqualifying a potential healthy donor was carried out on data sets based on either the published literature or our real-life data. For both data sets, we calculated the total cost to qualify a single donor according to the optimal order of tests, suggested by the algorithm. Results. Applying the algorithm to the published literature revealed potential savings of 94.2% of the cost of screening a potential donor and 7.05% of the cost to qualify a single donor. In our cohort of 87 volunteers, 53 were not eligible for donation. Of 34 potential donors, 10 were disqualified due to abnormal lab tests. Applying our algorithm to optimize the order of tests, the average cost for screening a potential donor resulted in potential savings of 49.9% and a 21.3% savings in the cost to qualify a single donor. Conclusions. Improving the order and timing of the screening tests of potential FMT stool donors can decrease the costs by about 50% per subject.<br><br>HIGHLIGHTS: What is known:Fecal microbial transplantation (FMT) is the transfer of microbiome from healthy donors to patients.Fecal donors undergo multiple strict screening tests to exclude any transmissible disease.Screening tests of potential fecal donors is expensive and time consuming.FMT is the most efficient treatment for recurrent C difficile infection.What is new here:An algorithm to optimize the order of donors' screening tests in terms of cost was defined.Optimizing the order tests can save nearly 50% in costs of screening a potential donor.}, }
@article {pmid38873568, year = {2024}, author = {Shang, Z and Pai, L and Patil, S}, title = {Unveiling the dynamics of gut microbial interactions: a review of dietary impact and precision nutrition in gastrointestinal health.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1395664}, pmid = {38873568}, issn = {2296-861X}, abstract = {The human microbiome, a dynamic ecosystem within the gastrointestinal tract, plays a pivotal role in shaping overall health. This review delves into six interconnected sections, unraveling the intricate relationship between diet, gut microbiota, and their profound impact on human health. The dance of nutrients in the gut orchestrates a complex symphony, influencing digestive processes and susceptibility to gastrointestinal disorders. Emphasizing the bidirectional communication between the gut and the brain, the Brain-Gut Axis section highlights the crucial role of dietary choices in physical, mental, and emotional well-being. Autoimmune diseases, particularly those manifesting in the gastrointestinal tract, reveal the delicate balance disrupted by gut microbiome imbalances. Strategies for reconciling gut microbes through diets, precision nutrition, and clinical indications showcase promising avenues for managing gastrointestinal distress and revolutionizing healthcare. From the Low-FODMAP diet to neuro-gut interventions, these strategies provide a holistic understanding of the gut's dynamic world. Precision nutrition, as a groundbreaking discipline, holds transformative potential by tailoring dietary recommendations to individual gut microbiota compositions, reshaping the landscape of gastrointestinal health. Recent advancements in clinical indications, including exact probiotics, fecal microbiota transplantation, and neuro-gut interventions, signify a new era where the gut microbiome actively participates in therapeutic strategies. As the microbiome takes center stage in healthcare, a paradigm shift toward personalized and effective treatments for gastrointestinal disorders emerges, reflecting the symbiotic relationship between the human body and its microbial companions.}, }
@article {pmid38871148, year = {2025}, author = {Paaske, SE and Baumwall, SMD and Rubak, T and Birn, FH and Rågård, N and Kelsen, J and Hansen, MM and Svenningsen, L and Krarup, AL and Fernis, CMC and Neumann, A and Lødrup, AB and Glerup, H and Vinter-Jensen, L and Helms, M and Erikstrup, LT and Grosen, AK and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Real-world Effectiveness of Fecal Microbiota Transplantation for First or Second Clostridioides difficile Infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {23}, number = {4}, pages = {602-611.e8}, doi = {10.1016/j.cgh.2024.05.038}, pmid = {38871148}, issn = {1542-7714}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/therapy/mortality ; Male ; Aged ; Female ; Middle Aged ; Aged, 80 and over ; Denmark ; Treatment Outcome ; Clostridioides difficile/isolation &amp; purification ; Diarrhea/therapy/microbiology ; Cohort Studies ; Recurrence ; }, abstract = {BACKGROUND &amp; AIMS: Clostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI, but its use for first or second CDI remains experimental. We aimed to investigate the effectiveness of FMT for first or second CDI in a real-world clinical setting.<br><br>METHODS: This multi-site Danish cohort study included patients with first or second CDI treated with FMT from June 2019 to February 2023. The primary outcome was cure of C.&#xa0;difficile-associated diarrhea (CDAD) 8 weeks after the last FMT treatment. Secondary outcomes included CDAD cure 1 and 8 weeks after the first FMT treatment and 90-day mortality following positive C.&#xa0;difficile test.<br><br>RESULTS: We included 467 patients, with 187 (40%) having their first CDI. The median patient age was 73 years (interquartile range [IQR], 58-82 years). Notably, 167 (36%) had antibiotic-refractory CDI, 262 (56%) had severe CDI, and 89 (19%) suffered from fulminant CDI. Following the first FMT treatment, cure of CDAD was achieved in 353 patients (76%; 95% confidence interval [CI], 71%-79%) at week 1. At week 8, 255 patients (55%; 95% CI, 50%-59%) maintained sustained effect. In patients without initial effect, repeated FMT treatments led to an overall cure of CDAD in 367 patients (79%; 95% CI, 75%-82%). The 90-day mortality was 10% (95% CI, 8%-14%).<br><br>CONCLUSION: Repeated FMT treatments demonstrate high effectiveness in managing patients with first or second CDI. Forwarding FMT in CDI treatment guidelines could improve patient survival.<br><br>CLINICALTRIALS: gov, Number: NCT03712722.}, }
@article {pmid38870892, year = {2024}, author = {Dubois, L and Valles-Colomer, M and Ponsero, A and Helve, O and Andersson, S and Kolho, KL and Asnicar, F and Korpela, K and Salonen, A and Segata, N and de Vos, WM}, title = {Paternal and induced gut microbiota seeding complement mother-to-infant transmission.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {6}, pages = {1011-1024.e4}, doi = {10.1016/j.chom.2024.05.004}, pmid = {38870892}, issn = {1934-6069}, mesh = {Humans ; Male ; Female ; *Infant, Newborn/growth &amp; development ; *Gastrointestinal Microbiome ; Cesarean Section ; Antibiotic Prophylaxis ; Fecal Microbiota Transplantation ; Biodiversity ; Parturition ; Metagenomics ; Feces/microbiology ; }, abstract = {Microbial colonization of the neonatal gut involves maternal seeding, which is partially disrupted in cesarean-born infants and after intrapartum antibiotic prophylaxis. However, other physically close individuals could complement such seeding. To assess the role of both parents and of induced seeding, we analyzed two longitudinal metagenomic datasets (health and early life microbiota [HELMi]: N = 74 infants, 398 samples, and SECFLOR: N = 7 infants, 35 samples) with cesarean-born infants who received maternal fecal microbiota transplantation (FMT). We found that the father constitutes a stable source of strains for the infant independently of the delivery mode, with the cumulative contribution becoming comparable to that of the mother after 1 year. Maternal FMT increased mother-infant strain sharing in cesarean-born infants, raising the average bacterial empirical growth rate while reducing pathogen colonization. Overall, our results indicate that maternal seeding is partly complemented by that of the father and support the potential of induced seeding to restore potential deviations in this process.}, }
@article {pmid38868519, year = {2024}, author = {Wang, L and Tu, YX and Chen, L and Yu, KC and Wang, HK and Yang, SQ and Zhang, Y and Zhang, SJ and Song, S and Xu, HL and Yin, ZC and Feng, MQ and Yue, JQ and Huang, XH and Tang, T and Wei, SZ and Liang, XJ and Chen, ZX}, title = {Black rice diet alleviates colorectal cancer development through modulating tryptophan metabolism and activating AHR pathway.}, journal = {iMeta}, volume = {3}, number = {1}, pages = {e165}, pmid = {38868519}, issn = {2770-596X}, abstract = {Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.}, }
@article {pmid38867928, year = {2023}, author = {Chen, AT and Zhang, J and Zhang, Y}, title = {Gut microbiota in heart failure and related interventions.}, journal = {iMeta}, volume = {2}, number = {3}, pages = {e125}, pmid = {38867928}, issn = {2770-596X}, abstract = {Heart failure (HF) is a sophisticated syndrome with structural or functional impairment of ventricular filling or ejection of blood, either causing symptoms and signs or being asymptomatic. HF is a major global health issue affecting about 64.3 million people worldwide. The gut microbiota refers to the complex ecosystem of microorganisms, mainly bacteria, in the gut. Studies have revealed that the gut microbiota is associated with many diseases ranging from neurodegenerative diseases to inflammatory bowel disease and cardiovascular diseases. The gut hypothesis of HF suggests that low cardiac output and systemic circulation congestion would cause insufficient intestinal perfusion, leading to ischemia and intestinal barrier dysfunction. The resulting bacterial translocation would contribute to inflammation. Recent studies have refined the hypothesis that changes of metabolites in the gut microbiota have a close relationship with HF. Thus, the gut microbiota has emerged as a potential therapeutic target for HF due to both its critical role in regulating host physiology and metabolism and its pivotal role in the development of HF. This review article aims to provide an overview of the current understanding of the gut microbiota's involvement in HF, including the introduction of the gut hypothesis of HF, its association with HF progression, the potential mechanisms involved mediated by the gut microbiota metabolites, and the impact of various interventions on the gut microbiota, including dietary interventions, probiotic therapy, fecal microbiota transplantation, antibiotics, and so on. While the gut hypothesis of HF is refined with up-to-date knowledge and the gut microbiota presents a promising target for HF therapy, further research is still needed to further understand the underlying mechanisms between gut microbiota and HF, the efficacy of these interventions, and contribute to the health of HF patients.}, }
@article {pmid38867886, year = {2024}, author = {Jia, X and Wang, Q and Liu, M and Ding, JY}, title = {The interplay between gut microbiota and the brain-gut axis in Parkinson's disease treatment.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1415463}, pmid = {38867886}, issn = {1664-2295}, abstract = {This study delves into the pivotal role of the gut microbiota and the brain-gut axis in Parkinson's Disease (PD), a neurodegenerative disorder with significant motor and non-motor implications. It posits that disruptions in gut microbiota-dysbiosis-and alterations in the brain-gut axis contribute to PD's pathogenesis. Our findings highlight the potential of the gastrointestinal system's early involvement in PD, suggested by the precedence of gastrointestinal symptoms before motor symptoms emerge. This observation implies a possible gut-originated disease pathway. The analysis demonstrates that dysbiosis in PD patients leads to increased intestinal permeability and systemic inflammation, which in turn exacerbates neuroinflammation and neurodegeneration. Such insights into the interaction between gut microbiota and the brain-gut axis not only elucidate PD's underlying mechanisms but also pave the way for novel therapeutic interventions. We propose targeted treatment strategies, including dietary modifications and fecal microbiota transplantation, aimed at modulating the gut microbiota. These approaches hold promise for augmenting current PD treatment modalities by alleviating both motor and non-motor symptoms, thereby potentially improving patient quality of life. This research underscores the significance of the gut microbiota in the progression and treatment of PD, advocating for an integrated, multidisciplinary approach to develop personalized, efficacious management strategies for PD patients, combining insights from neurology, microbiology, and nutritional science.}, }
@article {pmid38867599, year = {2024}, author = {Ma, C and Yin, B and Hu, X}, title = {Advances in clinical treatment of liver disease: fecal microbiota transplantation for liver disease.}, journal = {Minerva medica}, volume = {}, number = {}, pages = {}, doi = {10.23736/S0026-4806.24.09363-7}, pmid = {38867599}, issn = {1827-1669}, }
@article {pmid38866215, year = {2024}, author = {Chen, CY and Wang, YF and Lei, L and Zhang, Y}, title = {Impacts of microbiota and its metabolites through gut-brain axis on pathophysiology of major depressive disorder.}, journal = {Life sciences}, volume = {351}, number = {}, pages = {122815}, doi = {10.1016/j.lfs.2024.122815}, pmid = {38866215}, issn = {1879-0631}, mesh = {Humans ; *Depressive Disorder, Major/physiopathology/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; *Brain-Gut Axis/physiology ; Animals ; Brain/metabolism/physiopathology ; Tryptophan/metabolism ; }, abstract = {Major depressive disorder (MDD) is characterized by a high rate of recurrence and disability, which seriously affects the quality of life of patients. That's why a deeper understanding of the mechanisms of MDD pathology is an urgent task, and some studies have found that intestinal symptoms accompany people with MDD. The microbiota-gut-brain axis is the bidirectional communication between the gut microbiota and the central nervous system, which was found to have a strong association with the pathogenesis of MDD. Previous studies have focused more on the communication between the gut and the brain through neuroendocrine, neuroimmune and autonomic pathways, and the role of gut microbes and their metabolites in depression is unclear. Metabolites of intestinal microorganisms (e.g., tryptophan, kynurenic acid, indole, and lipopolysaccharide) can participate in the pathogenesis of MDD through immune and inflammatory pathways or by altering the permeability of the gut and blood-brain barrier. In addition, intestinal microbes can communicate with intestinal neurons and glial cells to affect the integrity and function of intestinal nerves. However, the specific role of gut microbes and their metabolites in the pathogenesis of MDD is not well understood. Hence, the present review summarizes how gut microbes and their metabolites are directly or indirectly involved in the pathogenesis of MDD.}, }
@article {pmid38862291, year = {2024}, author = {Gopalarathinam, R and Sankar, R and Zhao, SS}, title = {Role of Anti-Inflammatory Diet and Fecal Microbiota Transplant in Psoriatic Arthritis.}, journal = {Clinical therapeutics}, volume = {46}, number = {7}, pages = {588-596}, doi = {10.1016/j.clinthera.2024.05.005}, pmid = {38862291}, issn = {1879-114X}, mesh = {Humans ; *Arthritis, Psoriatic/therapy/immunology/microbiology ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Diet, Mediterranean ; Dietary Supplements ; }, abstract = {PURPOSE: Psoriatic arthritis (PsA) is a chronic inflammatory condition with complex and heterogenous manifestations. Although a myriad of treatment options including biologic medications are available to alleviate symptoms and slow disease progression, there is currently no cure for this condition. There has been a recent emergence of understanding about the relationship between the gut microbiome and immune-mediated inflammatory diseases. This has generated interest in the potential role of dietary interventions, particularly anti-inflammatory diets, and fecal microbiota transplant (FMT) as novel therapeutic approaches. The purpose of this narrative review is to examine the role of an anti-inflammatory diet and FMT in turn and whether their combination may offer alternate approaches for the management of PsA.<br><br>METHODS: Our non-systematic narrative review was informed by a literature search using PubMed and Google Scholar using the terms anti-inflammatory diet, FMT, nutrition supplements, and PsA. Preclinical studies and non-English language articles were excluded when synthesizing the narrative review.<br><br>FINDINGS: Current randomized controlled trials (RCTs) and observational evidence suggest that a hypocaloric diet or Mediterranean diet can help achieve weight loss among PsA patients who are overweight or obese, which in turn reduces inflammation and improves disease activity. However, there is no strong data to support the beneficial effects of intermittent fasting, vitamin supplements, turmeric supplements, probiotics, or omega-3 fatty acid supplements in PsA. Current evidence on the use of FMT in PsA is limited as only one small RCT has been conducted which did not demonstrate efficacy for improving clinical symptoms.<br><br>IMPLICATIONS: Clinicians can consider recommending hypocaloric or Mediterranean diets as an adjunct to standard management of PsA, possibly under the guidance of a dietician. Further research is needed to explore the beneficial effects of the synergistic role of combining an anti-inflammatory diet with FMT in PsA.}, }
@article {pmid38858775, year = {2024}, author = {Lin, D and Hu, D and Song, Y and He, X and Wu, L}, title = {Long-term efficacy of washed microbiota transplantation in overweight patients.}, journal = {European journal of clinical investigation}, volume = {54}, number = {10}, pages = {e14260}, doi = {10.1111/eci.14260}, pmid = {38858775}, issn = {1365-2362}, support = {2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; 2023M740782//China Postdoctoral Science Foundation/ ; 20221232//the Scientific Research Projects of Guangdong Bureau of Traditional Chinese Medicine/ ; B2022209//Medical Scientific Research Foundation of Guangdong Province/ ; 2021KCXTD025//Guangdong Innovation Research Team for Higher Education/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; *Overweight/therapy ; *Body Mass Index ; *Fecal Microbiota Transplantation/methods ; Retrospective Studies ; *Gastrointestinal Microbiome ; Adult ; Blood Glucose/metabolism ; Treatment Outcome ; Blood Pressure/physiology ; Aged ; Atherosclerosis/therapy ; Lipids/blood ; }, abstract = {BACKGROUND: Faecal microbiota transplantation holds promise in mitigating fat accumulation and improving obesity. This study aimed to evaluate the long-term efficacy of washed microbiota transplantation (WMT) among overweight patients.<br><br>METHODS: The clinical data pertaining to the treatment of patients with WMT were collected retrospectively. Compared alterations in body mass index (BMI), blood glucose, blood lipids and blood pressure prior to and following WMT treatment. Comprehensive efficacy evaluation and atherosclerosis cardiovascular disease (ASCVD) grading evaluation were carried out, with an analysis of gut microbiota composition before and after WMT.<br><br>RESULTS: A total of 186 patients were included (80 overweight, 106 normal weight). WMT not only had the effect of improving overweight patients to the normal weight patients (p&#x2009;<&#x2009;.001), but also could significantly reduce BMI in the long term by restoring gut microbiota homeostasis (p&#x2009;<&#x2009;.001). In addition, the BMI improvement value of multi course was more significant than that of single course or double course. WMT had a significant ASCVD downgrade effect on the high-risk and medium-risk groups outside 1&#x2009;year, while it did not increase the risk of upgrading ASCVD for low-risk group.<br><br>CONCLUSIONS: WMT could significantly reduce the BMI of overweight patients and still had an improvement effect in the long term.}, }
@article {pmid38858330, year = {2024}, author = {Guo, Q and Cheng, Y and Li, T and Huang, J and Li, J and Zhang, Z and Qu, Y}, title = {The Gut Microbiota Contributes to the Development of LPS-Induced Orchitis by Disrupting the Blood-Testosterone Barrier in Mice.}, journal = {Reproductive sciences (Thousand Oaks, Calif.)}, volume = {31}, number = {11}, pages = {3379-3390}, pmid = {38858330}, issn = {1933-7205}, support = {XYB201910//Doctoral Starting Up Foundation of the Heilongjiang Bayi Agricultural University/ ; LH2023C080//Natural Science Foundation of Heilongjiang Province of China/ ; 2023M731028//China Postdoctoral Science Foundation/ ; 2021ZX12B03//Heilongjiang Province Hundred Million Project Science and Technology Major project/ ; 32072758//National Natural Science Foundation of China/ ; LBH-Q20054//Heilongjiang Postdoctoral Found/ ; }, mesh = {Animals ; Male ; *Orchitis/microbiology/chemically induced ; *Gastrointestinal Microbiome/drug effects ; *Lipopolysaccharides/pharmacology ; *Testosterone/blood ; Mice ; *Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Blood-Testis Barrier/drug effects/metabolism ; Testis/drug effects/metabolism ; Disease Models, Animal ; }, abstract = {Orchitis is a frequent inflammatory reproductive disease that causes male infertility and a decline in sperm quality. Gut microbiota can regulate systemic and local inflammation, spermatogenesis and blood-testosterone barrier (BTB). In this study, we investigated correlation between gut microbiota and orchitis by establishing a mouse gut microbiota imbalance model induced by antibiotics (ABX) treatment and orchitis model induced by lipopolysaccharide (LPS) infection. Based on these two models, 16s rRNA sequencing and feces microbiota transplantation (FMT) experiments were combined to examine the function and regulatory mechanisms of the gut microbiota in host defense against orchitis. Compared with control mice, gut microbiota imbalance resulted in increasing inflammatory responses, modulating oxidative stress related enzyme activity, testosterone levels and the permeability of blood testosterone barrier, which are restored after FMT. Subsequently, we tested the relationship between the gut microbiota imbalance and testicular inflammation severity in orchitis. It was found that the ABX and LPS co-treated mice had more severe inflammatory responses, lower testosterone levels and greater permeability of the BTB than the LPS-treated mice, but these changes could be partially recovered by gut microbiota transplantation. In conclusion, these above results proved for the first time that gut microbiota is involved in the pathogenesis of orchitis, which laid a good foundation for the subsequent development of anti-orchitis drugs and probiotic targeting intestinal flora.}, }
@article {pmid38858151, year = {2024}, author = {Skjevling, L and Goll, R and Hanssen, HM and Johnsen, PH}, title = {Faecal microbiota transplantation (FMT) in Norwegian outpatients with mild to severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): protocol for a 12-month randomised double-blind placebo-controlled trial.}, journal = {BMJ open}, volume = {14}, number = {6}, pages = {e073275}, pmid = {38858151}, issn = {2044-6055}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Fatigue Syndrome, Chronic/therapy ; Double-Blind Method ; Norway ; Randomized Controlled Trials as Topic ; Adult ; Gastrointestinal Microbiome ; Treatment Outcome ; Female ; Male ; }, abstract = {INTRODUCTION: The observed alteration of the intestinal microbiota in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the effect of transferring a healthy gut flora from a faecal donor using a faecal microbiota transplantation (FMT) will be explored in this trial.<br><br>METHODS AND ANALYSIS: This is a protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial, with 12 months follow-up. 80 participants will be included and randomised (1:1:2) to either donor FMT (from two different donors) or placebo (autologous FMT). Participants will be included by the International Clinical Criteria for ME/CFS. The clinical measures of ME/CFS and disease activity include Modified DePaul Questionnaire, Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), 36-Item Short Form Health Survey (SF-36), ROMA IV criteria, Food Frequency Questionnaire, Repeatable Battery for the Assessment of Neuropsychological Status, heart rate variability testing and reports on the use of antibiotics and food supplements, as well as biobanking of blood, urine and faeces.The primary endpoint is proportion with treatment success in FSS score in donor versus autologous FMT group 3 months after treatment. Treatment success is defined as an FSS improvement of more than 1.2 points from baseline at 3 months after treatment. Adverse events will be registered throughout the study.<br><br>ETHICS AND DISSEMINATION: The Regional Committee for Medical Research Ethics Northern Norway has approved the study. The study has commenced in May 2019. Findings will be disseminated in international peer-reviewed journal(s), submitted to relevant conferences, and trial participants will be informed via phone calls.<br><br>TRIAL REGISTRATION NUMBER: NCT03691987.}, }
@article {pmid38857378, year = {2024}, author = {Xu, R and Feng, N and Li, Q and Wang, H and Li, L and Feng, X and Su, Y and Zhu, W}, title = {Pectin supplementation accelerates post-antibiotic gut microbiome reconstitution orchestrated with reduced gut redox potential.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {38857378}, issn = {1751-7370}, support = {32272891//National Natural Science Foundation of China/ ; 2022YFD1300402//National Key Research and Development Program of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Pectins/metabolism ; *Dysbiosis/microbiology ; *Oxidation-Reduction ; Rats ; *Anti-Bacterial Agents/pharmacology ; *Dietary Supplements ; Male ; *Feces/microbiology ; Fecal Microbiota Transplantation ; Rats, Sprague-Dawley ; Bacteria/classification/metabolism/isolation &amp; purification/drug effects/genetics ; Enterobacteriaceae/drug effects/metabolism ; }, abstract = {Antibiotic-induced gut dysbiosis (AID) presents a big challenge to host health, and the recovery from this dysbiosis is often slow and incomplete. AID is typically characterized by elevation in redox potential, Enterobacteriaceae load, and aerobic metabolism. In our previous study, a pectin-enriched diet was demonstrated to decrease fecal redox potential and modulate the gut microbiome. Therefore, we propose that pectin supplementation may modulate gut redox potential and favor post-antibiotic gut microbiome reconstitution from dysbiosis. In the present study, rats with AIDwere used to investigate the effects of pectin supplementation on post-antibiotic gut microbiome reconstitution from dysbiosis. The results showed that pectin supplementation accelerated post-antibiotic reconstitution of gut microbiome composition and function and led to enhancement of anabolic reductive metabolism and weakening of catabolic oxidative pathways. These results were corroborated by the measurement of redox potential, findings suggesting that pectin favors post-antibiotic recovery from dysbiosis. Pectin-modulated fecal microbiota transplantation accelerated the decrease in antibiotics-elevated redox potential and Enterobacteriaceae load similarly to pectin supplementation. Moreover, both pectin supplementation and Pectin-modulated fecal microbiota transplantation enriched anaerobic members, primarily from Lachnospiraceae orchestration with enhancement of microbial reductive metabolism in post-antibiotic rats. These findings suggested that pectin supplementation accelerated post-antibiotic gut microbiome reconstitution orchestrated with reduced gut redox potential and that the effect of pectin on redox potential was mediated by remodeling of the intestinal microbiota.}, }
@article {pmid38855295, year = {2024}, author = {Hazan, S and Haroon, J and Jordan, S and Walker, SJ}, title = {Correction to: Improvements in Gut Microbiome Composition and Clinical Symptoms Following Familial Fecal Microbiota Transplantation in a Nineteen-Year-Old Adolescent With Severe Autism.}, journal = {Journal of medical cases}, volume = {15}, number = {6}, pages = {115}, pmid = {38855295}, issn = {1923-4163}, abstract = {[This corrects the article DOI: 10.14740/jmc4209.].}, }
@article {pmid38854967, year = {2024}, author = {Wanyi, Z and Jiao, Y and Wen, H and Bin, X and Xuefei, W and Lan, J and Liuyin, Z}, title = {Bidirectional communication of the gut-brain axis: new findings in Parkinson's disease and inflammatory bowel disease.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1407241}, pmid = {38854967}, issn = {1664-2295}, abstract = {Parkinson's disease (PD) and inflammatory bowel disease (IBD) are the two chronic inflammatory diseases that are increasingly affecting millions of people worldwide, posing a major challenge to public health. PD and IBD show similarities in epidemiology, genetics, immune response, and gut microbiota. Here, we review the pathophysiology of these two diseases, including genetic factors, immune system imbalance, changes in gut microbial composition, and the effects of microbial metabolites (especially short-chain fatty acids). We elaborate on the gut-brain axis, focusing on role of gut microbiota in the pathogenesis of PD and IBD. In addition, we discuss several therapeutic strategies, including drug therapy, fecal microbiota transplantation, and probiotic supplementation, and their potential benefits in regulating intestinal microecology and relieving disease symptoms. Our analysis will provide a new understanding and scientific basis for the development of more effective therapeutic strategies for these diseases.}, }
@article {pmid38853707, year = {2024}, author = {Ni, S and Huang, X and Li, X and Shi, C and Fan, M and Zhao, L and Rong, Z and Zhang, H}, title = {METTL3 Promotes Nucleus Pulposus Cell Senescence in Intervertebral Disc Degeneration by Regulating TLR2 m6A Methylation and Gut Microbiota.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {79}, number = {8}, pages = {}, doi = {10.1093/gerona/glae150}, pmid = {38853707}, issn = {1758-535X}, support = {82002353//National Natural Science Foundation of China/ ; //Young and Middle-aged Discipline Leader Cultivation Project of He'nan Health/ ; }, mesh = {Animals ; *Toll-Like Receptor 2/metabolism/genetics ; *Gastrointestinal Microbiome ; Rats ; *Methyltransferases/metabolism/genetics ; *Nucleus Pulposus/metabolism/pathology ; *Cellular Senescence ; *Intervertebral Disc Degeneration/metabolism/pathology/microbiology ; *Rats, Sprague-Dawley ; Male ; Disease Models, Animal ; Methylation ; Adenosine/analogs &amp; derivatives/metabolism ; }, abstract = {BACKGROUND: Nucleus pulposus cell (NPC) senescence in intervertebral disc (IVD) tissue is the major pathological cause of intervertebral disc degeneration (IDD). N6-methyladenosine (m6A) methylation and gut microbiota play important roles in the progression of IDD. This study investigated whether methyltransferase-like 3 (METTL3) regulates TLR2 m6A modification and gut microbiota to influence NPC senescence.<br><br>METHODS: An IDD rat model was established by lumbar IVD puncture and NPCs were challenged with IL-1&#x3b2; to mimic IVD injury. IDD rats and IL-1&#x3b2;-exposed NPCs were treated with METTL3-interfering lentivirus and the TLR2 agonist Pam3CSK4. Compositional changes in the rat gut microbiota were analyzed and fecal microbiota transplantation procedures were used. NPC senescence, cell cycle, and the expression of senescence-associated secretory phenotype (SASP) factors were assessed. The m6A enrichment of TLR2 and the binding of IGF2BP1 to TLR2 mRNA were examined.<br><br>RESULTS: METTL3 and TLR2 were highly expressed in IDD rats. METTL3 silencing attenuated senescent phenotypes and reduced secretion of SASP factors. Pam3CSK4 reversed the beneficial effects of METTL3 silencing on NPC senescence and IVD injury. METTL3 stabilized TLR2 mRNA in an IGF2BP1-dependent manner. METTL3 silencing restored specific gut microbiota levels in IDD rats, which was further reversed by administration of Pam3CSK4. Fecal microbiota from METTL3 silenced IDD rats altered the pathological phenotypes of IDD rats.<br><br>CONCLUSIONS: These results demonstrate the beneficial effects of METTL3 silencing on NPC senescence and amelioration of IVD injury, involving modulation of TLR2 m6A modification and gut microbiota. These findings support METTL3 silencing as a potential therapeutic target for IDD.}, }
@article {pmid38852729, year = {2024}, author = {Liu, L and Zhao, Z and Liu, H and Xia, X and Ai, C and Song, S and Yan, C}, title = {Haematococcus pluvialis polysaccharides improve microbiota-driven gut epithelial and vascular barrier and prevent alcoholic steatohepatitis development.}, journal = {International journal of biological macromolecules}, volume = {274}, number = {Pt 1}, pages = {133014}, doi = {10.1016/j.ijbiomac.2024.133014}, pmid = {38852729}, issn = {1879-0003}, mesh = {*Chlorophyceae/chemistry ; *Polysaccharides/pharmacology ; Male ; Animals ; Mice ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome/drug effects ; Ethanol/toxicity ; Epithelial Cells/drug effects ; *Intestinal Mucosa/drug effects/metabolism/microbiology ; *Fatty Liver/prevention &amp; control ; Chemical and Drug Induced Liver Injury/drug therapy ; Capillary Permeability/drug effects ; Feces/microbiology ; Oxidative Stress/drug effects ; }, abstract = {Algal polysaccharides possess many biological activities and health benefits, such as antioxidant, anti-tumor, anti-coagulant, and immunomodulatory potential. Gut microbiota has emerged as one of the major contributor in mediating the health benefits of algal polysaccharides. In this study we showed that Haematococcus pluvialis polysaccharides (HPP) decreased serum transaminase levels and hepatic triglyceride content, alleviated inflammation and oxidative stress in the liver of chronic and binge ethanol diet-fed mice. Furthermore, HPP reduced endotoxemia, improved gut microbiota dysbiosis, inhibited epithelial barrier disruption and gut vascular barrier (GVB) damage in ethanol diet-fed mice. Co-housing vehicle-fed mice with HPP-fed mice alleviated ethanol-induced liver damage and endotoxemia. Moreover, fecal microbiota transplantation from HPP-fed mice into antibiotic-induced microbiota-depleted recipients also alleviated ethanol-induced liver injury and improved gut epithelial and vascular barrier. Our study demonstrated that HPP ameliorated ethanol-induced gut epithelial and vascular barrier dysfunction through alteration of gut microbiota, therefore preventing alcoholic liver damage.}, }
@article {pmid38852024, year = {2024}, author = {Georgin-Lavialle, S and Delplanque, M and Bachmeyer, C and Savey, L and Sokol, H and , }, title = {Clostridioides difficile infection as a potential trigger for Familial Mediterranean Fever attacks and fecal transplantation as a rescue.}, journal = {European journal of internal medicine}, volume = {128}, number = {}, pages = {148-149}, doi = {10.1016/j.ejim.2024.05.023}, pmid = {38852024}, issn = {1879-0828}, mesh = {Adult ; Female ; Humans ; Male ; *Clostridioides difficile ; *Clostridium Infections/therapy ; *Familial Mediterranean Fever/complications ; *Fecal Microbiota Transplantation ; Middle Aged ; Aged ; }, }
@article {pmid38850943, year = {2024}, author = {Ye, L and Chen, H and Wang, J and Tsim, KWK and Wang, Y and Shen, X and Lei, H and Liu, Y}, title = {Aflatoxin B1-induced liver pyroptosis is mediated by disturbing the gut microbial metabolites: The roles of pipecolic acid and norepinephrine.}, journal = {Journal of hazardous materials}, volume = {474}, number = {}, pages = {134822}, doi = {10.1016/j.jhazmat.2024.134822}, pmid = {38850943}, issn = {1873-3336}, mesh = {Animals ; *Aflatoxin B1/toxicity/metabolism ; *Pyroptosis/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Pipecolic Acids/metabolism ; Humans ; *Liver/drug effects/metabolism/pathology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Norepinephrine/metabolism ; Hep G2 Cells ; Male ; Mice, Inbred C57BL ; Toll-Like Receptor 4/metabolism ; Mice ; Feces/microbiology ; }, abstract = {The disturbed gut microbiota is a key factor in activating the aflatoxin B1 (AFB1)-induced liver pyroptosis by promoting inflammatory hepatic injury; however, the pathogen associated molecular pattern (PAMP) from disturbed gut microbiota and its mechanism in activating liver pyroptosis remain undefined. By transplanting AFB1-originated fecal microbiota and sterile fecal microbial metabolites filtrate, we determined the association of PAMP in AFB1-induced liver pyroptosis. Notably, AFB1-originated sterile fecal microbial metabolites filtrate were more active in triggering liver pyroptosis in mice, as compared to parental fecal microbiota. This result supported a critical role of the metabolic homeostasis of gut microbiota in AFB1-induced liver pyroptosis, rather than an injurious response to direct exposure of AFB1 in liver. Among the gut-microbial metabolites, pipecolic acid and norepinephrine were proposed to bind TLR4 and NLRP3, the upstream proteins of pyroptosis signaling pathway. Besides, the activations of TLR4 and NLRP3 were linearly correlated with the concentrations of pipecolic acid and norepinephrine in the serum of mice. In silenced expression of TLR4 and NLRP3 in HepG2 cells, pipecolic acid or norepinephrine did not able to activate hepatocyte pyroptosis. These results demonstrated the necessity of gut microbial metabolism in sustaining liver homeostasis, as well as the potential to provide new insights into targeted intervention for AFB1 hepatotoxicity.}, }
@article {pmid38848972, year = {2024}, author = {Zhou, H and Wang, X and She, Z and Huang, L and Wei, H and Yang, S and Wei, Z and Chen, H and Yang, B and Hu, Z and Feng, X and Zhu, P and Li, Z and Shen, J and Liu, H and Dong, H and Chen, G and Zhang, Q}, title = {Combining bioinformatics and multiomics strategies to investigate the key microbiota and active components of Liupao tea ameliorating hyperlipidemia.}, journal = {Journal of ethnopharmacology}, volume = {333}, number = {}, pages = {118438}, doi = {10.1016/j.jep.2024.118438}, pmid = {38848972}, issn = {1872-7573}, mesh = {Animals ; *Hyperlipidemias/drug therapy ; *Gastrointestinal Microbiome/drug effects ; *Molecular Docking Simulation ; Male ; Mice ; *Tea/chemistry ; Computational Biology ; Network Pharmacology ; Plant Extracts/pharmacology/chemistry ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects ; Hypolipidemic Agents/pharmacology/isolation &amp; purification/therapeutic use ; Disease Models, Animal ; Metabolomics ; Multiomics ; }, abstract = {Hyperlipidemia as a major health issue has attracted much public attention. As a geographical indication product of China, Liupao tea (LPT) is a typical representative of traditional Chinese dark tea that has shown good potential in regulating glucose and lipid metabolism. LPT has important medicinal value in hyperlipidemia prevention. However, the active ingredients and metabolic mechanisms by which LPT alleviates hyperlipidemia remain unclear.<br><br>AIM OF THE STUDY: This study aimed to systematically investigate the metabolic mechanisms and active ingredients of LPT extract in alleviating hyperlipidemia.<br><br>MATERIALS AND METHODS: Firstly, we developed a mouse model of hyperlipidemia to study the pharmacodynamics of LPT. Subsequently, network pharmacology and molecular docking were performed to predict the potential key active ingredients and core targets of LPT against hyperlipidemia. LC-MS/MS was used to validate the identity of key active ingredients in LPT with chemical standards. Finally, the effect and metabolic mechanisms of LPT extract in alleviating hyperlipidemia were investigated by integrating metabolomic, lipidomic, and gut microbiome analyses.<br><br>RESULTS: Results showed that LPT extract effectively improved hyperlipidemia by suppressing weight gain, remedying dysregulation of glucose and lipid metabolism, and reducing hepatic damage. Network pharmacology analysis and molecular docking suggested that four potential active ingredients and seven potential core targets were closely associated with roles for hyperlipidemia treatment. Ellagic acid, catechin, and naringenin were considered to be the key active ingredients of LPT alleviating hyperlipidemia. Additionally, LPT extract modulated the mRNA expression levels of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 associated with bile acid (BA) metabolism, mitigated the disturbances of BA and glycerophospholipid (GP) metabolism in hyperlipidemia mice. Combining fecal microbiota transplantation and correlation analysis, LPT extract effectively improved species diversity and abundance of gut microbiota, particularly the BA and GP metabolism-related gut microbiota, in the hyperlipidemia mice.<br><br>CONCLUSIONS: LPT extract ameliorated hyperlipidemia by modulating GP and BA metabolism by regulating Lactobacillus and Dubosiella, thereby alleviating hyperlipidemia. Three active ingredients of LPT served as the key factors in exerting an improvement on hyperlipidemia. These findings provide new insights into the active ingredients and metabolic mechanisms of LPT in improving hyperlipidemia, suggesting that LPT can be used to prevent and therapeutic hyperlipidemia.}, }
@article {pmid38848942, year = {2024}, author = {Nguyen, NN and Lin, CY and Tsai, WL and Huang, HY and Chen, CM and Tung, YT and Chen, YC}, title = {Natural sweetener glycyrrhizin protects against precocious puberty by modulating the gut microbiome.}, journal = {Life sciences}, volume = {350}, number = {}, pages = {122789}, doi = {10.1016/j.lfs.2024.122789}, pmid = {38848942}, issn = {1879-0631}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Glycyrrhizic Acid/pharmacology ; Animals ; Rats ; Male ; Female ; *Puberty, Precocious/prevention &amp; control/drug therapy ; *Sweetening Agents/pharmacology/adverse effects ; Humans ; Child ; Rats, Sprague-Dawley ; Fecal Microbiota Transplantation ; }, abstract = {AIMS: Precocious puberty (PP) may lead to many adverse outcomes. Recent evidence suggests that PP is a gut-brain disease. On the other hand, the use of glycyrrhizin, a natural sweetener, has become popular in the past decade. Glycyrrhizin possesses various health benefits, but its impact on PP has yet to be investigated. We aimed to explore the protective effects of glycyrrhizin against PP in both humans (observational) and animals (interventional).<br><br>MATERIALS AND METHODS: In the human cohort, we investigated the association between glycyrrhizin consumption and risk of PP. In the animal experiment, we observed puberty onset after feeding danazol-induced PP rats with glycyrrizin. Blood, fecal, and hypothalamic samples were harvested to evaluate potential mechanistic pathways. We also performed a fecal microbiota transplantation to confirm to causal relationship between glycyrrhizin and PP risk.<br><br>KEY FINDINGS: Glycyrrhizin exhibited a protective effect against PP in children (OR 0.60, 95%CI: 0.39-0.89, p = 0.013), primarily driven by its significance in girls, while no significant effect was observed in boys. This effect was consistent with findings in rodents. These benefits were achieved through the modulation of the gut microbiome, which functionally suppressed the hypothalamic-pituitary-gonadal axis and prevented PP progression. A fecal microbiota transplantation indicated that the causal correlation between glycyrrhizin intake and PP is mediated by the gut microbiome alterations.<br><br>SIGNIFICANCE: Our findings suggest that glycyrrhizin can protect against PP by altering the gut microbiome. Long term use of glycyrrhizin is safe and tolerable. Therefore, glycyrrhizin can serve as a safe and affordable complementary therapy for PP.}, }
@article {pmid38846356, year = {2024}, author = {Pfail, J and Drobner, J and Doppalapudi, K and Saraiya, B and Packiam, V and Ghodoussipour, S}, title = {The Role of Tumor and Host Microbiome on Immunotherapy Response in Urologic Cancers.}, journal = {Journal of cancer immunology}, volume = {6}, number = {1}, pages = {1-13}, pmid = {38846356}, issn = {2689-968X}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; }, abstract = {INTRODUCTION &amp; OBJECTIVE: The role of the microbiome in the development and treatment of genitourinary malignancies is just starting to be appreciated. Accumulating evidence suggests that the microbiome can modulate immunotherapy through signaling in the highly dynamic tumor microenvironment. Nevertheless, much is still unknown about the immuno-oncology-microbiome axis, especially in urologic oncology. The objective of this review is to synthesize our current understanding of the microbiome's role in modulating and predicting immunotherapy response to genitourinary malignancies.<br><br>METHODS: A literature search for peer-reviewed publications about the microbiome and immunotherapy response in bladder, kidney, and prostate cancer was conducted. All research available in PubMed, Google Scholar, clinicaltrials.gov, and bioRxiv up to September 2023 was analyzed.<br><br>RESULTS: Significant differences in urinary microbiota composition have been found in patients with genitourinary cancers compared to healthy controls. Lactic acid-producing bacteria, such as Bifidobacterium and Lactobacillus genera, may have value in augmenting BCG responsiveness to bladder cancer. BCG may also be a dynamic regulator of PD-L1. Thus, the combination of BCG and immune checkpoint inhibitors may be an effective strategy for bladder cancer management. In advanced renal cell carcinoma, studies show that recent antibiotic administration negatively impacts survival outcomes in patients undergoing immunotherapy, while administration of CBM588, a live bacterial product, is associated with improved progression-free survival. Specific bacterial taxa, such as Streptococcus salivarius, have been linked with response to pembrolizumab in metastatic castrate-resistant prostate cancer. Fecal microbiota transplant has been shown to overcome resistance and reduce toxicity to immunotherapy; it is currently being investigated for both kidney and prostate cancers.<br><br>CONCLUSIONS: Although the exact mechanism is unclear, several studies identify a symbiotic relationship between microbiota-centered interventions and immunotherapy efficacy. It is possible to improve immunotherapy responsiveness in genitourinary malignancies using the microbiome, but further research with more standardized methodology is warranted.}, }
@article {pmid38844081, year = {2024}, author = {Leng, Y and Zhang, X and Zhang, Q and Xia, J and Zhang, Y and Ma, C and Liu, K and Li, H and Hong, Y and Xie, Z}, title = {Gallic acid attenuates murine ulcerative colitis by promoting group 3 innate lymphocytes, affecting gut microbiota, and bile acid metabolism.}, journal = {The Journal of nutritional biochemistry}, volume = {131}, number = {}, pages = {109677}, doi = {10.1016/j.jnutbio.2024.109677}, pmid = {38844081}, issn = {1873-4847}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Gallic Acid/pharmacology ; *Bile Acids and Salts/metabolism ; *Colitis, Ulcerative/drug therapy/microbiology/metabolism/immunology ; *Lymphocytes/metabolism ; *Immunity, Innate/drug effects ; *Mice, Inbred C57BL ; Mice ; Male ; Cytokines/metabolism ; }, abstract = {Gallic acid (GA), a plant phenol that is widely distributed in fruits and vegetables, and exhibits a protective role against ulcerative colitis (UC). UC is an inflammatory disease characterized by immune response disorders. However, the role and mechanism of action of GA in gut immunity remain unknown. Here, we observed that GA treatment improved enteritis symptoms, decreased the concentrations of cytokines TNF-α, IFN-γ, IL-6, IL-17A, and IL-23, increased the concentrations of cytokines IL-10, TGF-β and IL-22, and increased the proportion of group 3 innate lymphoid cells (ILC3) in mesenteric lymph nodes and lamina propria. However, GA did not upregulate ILC3 or impair UC in antibody-treated sterile mice. Notably, transplantation of fecal bacteria derived from GA-treated UC mice, instead of UC mice, increased ILC3 levels. Therefore, we analyzed the gut microbiota and related metabolites to elucidate the mechanism promoting ILC3. We determined that GA treatment altered the diversity of the gut microbiota and activated the bile acid (BA) metabolic pathway. We evaluated three BAs, namely, UDCA, isoalloLCA, and 3-oxoLCA that were significantly upregulated after GA treatment, improved UC symptoms, and elevated the proportion of ILC3 in vivo and in vitro. Collectively, these data indicate that GA attenuates UC by elevating ILC3 proportion, regulating the gut microbiota, and impacting BA metabolism. Additionally, we highlight the modulatory effects of BAs on ILC3 for the first time. Our findings provide novel insights into the multiple roles of GA in alleviating UC and provide a mechanistic explanation that supports the dietary nutrition in UC therapy.}, }
@article {pmid38843950, year = {2024}, author = {El-Salhy, M and Gilja, OH and Hatlebakk, JG}, title = {Factors underlying the long-term efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome.}, journal = {Microbes and infection}, volume = {26}, number = {8}, pages = {105372}, doi = {10.1016/j.micinf.2024.105372}, pmid = {38843950}, issn = {1769-714X}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Bacteria/classification/genetics/isolation &amp; purification ; Dysbiosis/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; *Irritable Bowel Syndrome/therapy/microbiology ; *RNA, Ribosomal, 16S/genetics ; Surveys and Questionnaires ; Treatment Outcome ; }, abstract = {The long-term effects of the transplant dose, its administration route and repeated faecal microbiota transplantation (FMT) on the outcomes of FMT for patients with irritable bowel syndrome (IBS) are unknown. This study included 171 patients (125 females and 46 males): 90 g of donor feces was administered into the large intestine (LI) in 58, into the small intestine (SI) in 57, and into the SI twice (repeated SI) in 56. The patients provided a fecal sample and completed five questionnaires at the baseline and at 2 years after FMT. Fecal bacteria and the dysbiosis index were analyzed using 16S rRNA gene PCR DNA amplification/probe. The response rates at 2 years after FMT were 47.2%, 80.9%, and 76.6% in the LI, SI, and repeated-SI groups, respectively. The response rate was significantly higher in the SI and repeated SI groups than in the LI group. IBS symptoms at 2 years after FMT were less severe in the SI and repeated-SI groups than in the LI group. Fluorescent signals of several bacteria were significantly correlated with IBS symptoms and fatigue after FMT. No long-term adverse events were observed. In conclusion, administering the transplant to the SI increased the long-term response rate and reduced IBS symptom severity compared with administering it to the LI, and led to the long-term colonization of beneficial bacteria. There was no long-term difference between one and two FMT procedures (www.clinicaltrials.gov: NCT04236843).}, }
@article {pmid38841848, year = {2024}, author = {Montrose, JA and Kurada, S and Fischer, M}, title = {Current and future microbiome-based therapies in inflammatory bowel disease.}, journal = {Current opinion in gastroenterology}, volume = {40}, number = {4}, pages = {258-267}, pmid = {38841848}, issn = {1531-7056}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy/microbiology ; Inflammatory Bowel Diseases/microbiology/therapy ; Randomized Controlled Trials as Topic ; }, abstract = {PURPOSE OF REVIEW: The role of the microbiome and dysbiosis is increasingly recognized in the pathogenesis of inflammatory bowel disease (IBD). Intestinal microbiota transplant (IMT), previously termed fecal microbiota transplant has demonstrated efficacy in restoring a healthy microbiome and promoting gut health in recurrent Clostridioides difficile infection. Several randomized trials (RCTs) highlighted IMT's potential in treating ulcerative colitis, while smaller studies reported on its application in managing Crohn's disease and pouchitis.<br><br>RECENT FINDINGS: This review delves into the current understanding of dysbiosis in IBD, highlighting the distinctions in the microbiota of patients with IBD compared to healthy controls. It explores the mechanisms by which IMT can restore a healthy microbiome and provides a focused analysis of recent RCTs using IMT for inducing and maintaining remission in IBD. Lastly, we discuss the current knowledge gaps that limit its widespread use.<br><br>SUMMARY: The body of evidence supporting the use of IMT in IBD is growing. The lack of a standardized protocol impedes its application beyond clinical trials. Further research is needed to identify patient profile and disease phenotypes that benefit from IMT, to delineate key donor characteristics, optimize the delivery route, dosage, and frequency.}, }
@article {pmid38841589, year = {2024}, author = {Luo, ZQ and Huang, YJ and Chen, ZH and Lu, CY and Zhou, B and Gong, XH and Shen, Z and Wang, T}, title = {A decade of insight: bibliometric analysis of gut microbiota's role in osteoporosis (2014-2024).}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1409534}, pmid = {38841589}, issn = {2296-858X}, abstract = {PURPOSE: Osteoporosis represents a profound challenge to public health, underscoring the critical need to dissect its complex etiology and identify viable targets for intervention. Within this context, the gut microbiota has emerged as a focal point of research due to its profound influence on bone metabolism. Despite this growing interest, the literature has yet to see a bibliometric study addressing the gut microbiota's contribution to both the development and management of osteoporosis. This study aims to fill this gap through an exhaustive bibliometric analysis. Our objective is to uncover current research hotspots, delineate key themes, and identify future research trends. In doing so, we hope to provide direction for future studies and the development of innovative treatment methods.<br><br>METHODS: Relevant publications in this field were retrieved from the Web of Science Core Collection database. We used VOSviewer, CiteSpace, an online analysis platform and the R package "Bibliometrix" for bibliometric analysis.<br><br>RESULTS: A total of 529 publications (including 351 articles and 178 reviews) from 61 countries, 881 institutions, were included in this study. China leads in publication volume and boast the highest cumulative citation. Shanghai Jiao Tong University and Southern Medical University are the leading research institutions in this field. Nutrients contributed the largest number of articles, and J Bone Miner Res is the most co-cited journal. Of the 3,166 scholars who participated in the study, Ohlsson C had the largest number of articles. Li YJ is the most co-cited author. "Probiotics" and "inflammation" are the keywords in the research.<br><br>CONCLUSION: This is the first bibliometric analysis of gut microbiota in osteoporosis. We explored current research status in recent years and identified frontiers and hot spots in this research field. We investigate the impact of gut microbiome dysregulation and its associated inflammation on OP progression, a topic that has garnered international research interest in recent years. Additionally, our study delves into the potential of fecal microbiota transplantation or specific dietary interventions as promising avenues for future research, which can provide reference for the researchers who focus on this research filed.}, }
@article {pmid38841199, year = {2024}, author = {Karna, R and Babich, M}, title = {Fecal microbiota transplant in liver diseases: Current evidence and future directions.}, journal = {Clinical liver disease}, volume = {23}, number = {1}, pages = {e0154}, pmid = {38841199}, issn = {2046-2484}, }
@article {pmid38840756, year = {2024}, author = {Qin, H and Fu, Y and Deng, C and Chen, Y and Huang, K and Ruan, Y and Liu, K}, title = {The role of gut microbiota and the gut-lung axis in sepsis: A case study of a pregnant woman with severe rickettsial pneumonia and septic shock complicated by MODS.}, journal = {Clinical case reports}, volume = {12}, number = {6}, pages = {e8815}, pmid = {38840756}, issn = {2050-0904}, abstract = {KEY CLINICAL MESSAGE: In this case report, we describe the successful management of severe scrub typhus with pneumonia, sepsis, and multiple organ dysfunction in a pregnant woman. Despite initial challenges, the patient responded favorably to fecal microbiota transplantation and oral fecal microbiota capsule therapy.<br><br>ABSTRACT: Scrub typhus, caused by Orientia tsutsugamushi, can lead to severe multiorgan dysfunction and carries a mortality rate of up to 70% if not treated properly. In this report, we present the case of a 27-year-old pregnant woman at 18&#x2009;+&#x2009;6&#x2009;weeks gestation whose symptoms worsened 15&#x2009;days after onset and progressed to severe pneumonia with sepsis and multiple organ dysfunction syndrome. After the pathogen was confirmed by next-generation sequencing analysis of bronchoalveolar-lavage fluid and blood samples, the patient's treatment was switched to antiinfective chloramphenicol. The patient also underwent uterine evacuation due to a miscarriage. Extracorporeal membrane oxygenation was discontinued once the pulmonary infection significantly improved. Subsequently, the patient had recurrent diarrhea, abdominal distension, and difficulty eating. The antibiotic regimen was adjusted according to the drug sensitivity, but the diarrhea and abdominal distension still did not improve. Following a comprehensive multidisciplinary risk assessment, we initiated fecal microbiota transplantation and oral fecal microbiota capsule therapy. As a result, the patient's condition was effectively managed, and they were gradually discharged. Fecal microbiota transplantation may be a safe and effective treatment for severe pneumonia and shock in pregnant women. This has significant implications for maternal health. However, further clinical cases are required to observe its long-term effectiveness.}, }
@article {pmid38840189, year = {2024}, author = {Amati, AL and Ebert, R and Maier, L and Panah, AK and Schwandner, T and Sander, M and Reichert, M and Grau, V and Petzoldt, S and Hecker, A}, title = {Reduced preoperative serum choline esterase levels and fecal peritoneal contamination as potential predictors for the leakage of intestinal sutures after source control in secondary peritonitis.}, journal = {World journal of emergency surgery : WJES}, volume = {19}, number = {1}, pages = {21}, pmid = {38840189}, issn = {1749-7922}, support = {GU405/14-1//German Research Foundation (DFG)/ ; GU405/14-1//German Research Foundation (DFG)/ ; }, mesh = {Humans ; Female ; Male ; Retrospective Studies ; *Peritonitis/surgery ; Middle Aged ; Aged ; *Feces ; Sutures ; Anastomotic Leak ; Postoperative Complications ; Risk Factors ; Biomarkers/blood ; Laparotomy/methods/adverse effects ; }, abstract = {BACKGROUND: The high rate of stoma placement during emergency laparotomy for secondary peritonitis is a paradigm in need of change in the current fast-track surgical setting. Despite growing evidence for the feasibility of primary bowel reconstruction in a peritonitic environment, little data substantiate a surgeons' choice between a stoma and an anastomosis. The aim of this retrospective analysis is to identify pre- and intraoperative parameters that predict the leakage risk for enteric sutures placed during source control surgery (SCS) for secondary peritonitis.<br><br>METHODS: Between January 2014 and December 2020, 497 patients underwent SCS for secondary peritonitis, of whom 187 received a primary reconstruction of the lower gastro-intestinal tract without a diverting stoma. In 47 (25.1%) patients postoperative leakage of the enteric sutures was directly confirmed during revision surgery or by computed tomography. Quantifiable predictors of intestinal suture outcome were detected by multivariate analysis.<br><br>RESULTS: Length of intensive care, in-hospital mortality and failure of release to the initial home environment were significantly higher in patients with enteric suture leakage following SCS compared to patients with intact anastomoses (p&#x2009;<&#x2009;0.0001, p&#x2009;=&#x2009;0.0026 and p&#x2009;=0.0009, respectively). Reduced serum choline esterase (sCHE) levels and a high extent of peritonitis were identified as independent risk factors for insufficiency of enteric sutures placed during emergency laparotomy.<br><br>CONCLUSIONS: A preoperative sCHE&#x2009;<&#x2009;4.5 kU/L and generalized fecal peritonitis associate with a significantly higher incidence of enteric suture insufficiency after primary reconstruction of the lower gastro-intestinal tract in a peritonitic abdomen. These parameters may guide surgeons when choosing the optimal surgical procedure in the emergency setting.}, }
@article {pmid38839272, year = {2024}, author = {Bedke, T and Stumme, F and Tomczak, M and Steglich, B and Jia, R and Bohmann, S and Wittek, A and Kempski, J and Göke, E and Böttcher, M and Reher, D and Franke, A and Lennartz, M and Clauditz, T and Sauter, G and Fründt, T and Weidemann, S and Tiegs, G and Schramm, C and Gagliani, N and Pelczar, P and Huber, S}, title = {Protective function of sclerosing cholangitis on IBD.}, journal = {Gut}, volume = {73}, number = {8}, pages = {1292-1301}, pmid = {38839272}, issn = {1468-3288}, mesh = {*Cholangitis, Sclerosing/immunology/complications/microbiology ; Animals ; Mice ; *T-Lymphocytes, Regulatory/immunology ; *Inflammatory Bowel Diseases/microbiology/complications/immunology ; *Disease Models, Animal ; *Gastrointestinal Microbiome ; Humans ; Forkhead Transcription Factors/metabolism ; Colitis/microbiology/complications ; Male ; Fecal Microbiota Transplantation ; Female ; Feces/microbiology ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVE: There is a strong clinical association between IBD and primary sclerosing cholangitis (PSC), a chronic disease of the liver characterised by biliary inflammation that leads to strictures and fibrosis. Approximately 60%-80% of people with PSC will also develop IBD (PSC-IBD). One hypothesis explaining this association would be that PSC drives IBD. Therefore, our aim was to test this hypothesis and to decipher the underlying mechanism.<br><br>DESIGN: Colitis severity was analysed in experimental mouse models of colitis and sclerosing cholangitis, and people with IBD and PSC-IBD. Foxp3[+] Treg-cell infiltration was assessed by qPCR and flow cytometry. Microbiota profiling was carried out from faecal samples of people with IBD, PSC-IBD and mouse models recapitulating these diseases. Faecal microbiota samples collected from people with IBD and PSC-IBD were transplanted into germ-free mice followed by colitis induction.<br><br>RESULTS: We show that sclerosing cholangitis attenuated IBD in mouse models. Mechanistically, sclerosing cholangitis causes an altered intestinal microbiota composition, which promotes Foxp3[+] Treg-cell expansion, and thereby protects against IBD. Accordingly, sclerosing cholangitis promotes IBD in the absence of Foxp3[+] Treg cells. Furthermore, people with PSC-IBD have an increased Foxp3[+] expression in the colon and an overall milder IBD severity. Finally, by transplanting faecal microbiota into gnotobiotic mice, we showed that the intestinal microbiota of people with PSC protects against colitis.<br><br>CONCLUSION: This study shows that PSC attenuates IBD and provides a comprehensive insight into the mechanisms involved in this effect.}, }
@article {pmid38839189, year = {2024}, author = {Voth, E and Khanna, S}, title = {Rise to the Challenge: Master the Management of Clostridioides difficile Infection.}, journal = {Mayo Clinic proceedings}, volume = {99}, number = {6}, pages = {971-979}, doi = {10.1016/j.mayocp.2024.02.022}, pmid = {38839189}, issn = {1942-5546}, mesh = {Humans ; *Clostridium Infections/therapy/diagnosis ; *Anti-Bacterial Agents/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Clostridioides difficile ; Gastrointestinal Microbiome ; Risk Factors ; }, abstract = {Clostridioides difficile infection (CDI) is a significant public health challenge in the developed world. Although previously CDI was primarily a health care-acquired infection, there are now rising numbers of community-acquired cases in patients without traditional risk factors, such as antibiotic exposure. The landscape for the treatment of CDI has changed significantly during the past decade, including newer diagnostic tests, novel antibiotic regimens, and strategies for microbiome restoration in the form of traditional fecal microbiota transplant and approved live biotherapeutics in an effort to address the underlying pathophysiologic process of gut microbial dysbiosis. We present a concise review for clinicians on the diagnosis and management of both primary and recurrent CDI.}, }
@article {pmid38838972, year = {2024}, author = {Antman, G and Ritzer, L and Galor, A and Verticchio Vercellin, A and Siesky, BA and Alabi, D and Vayner, J and Segev, F and Harris, A}, title = {The relationship between dry eye disease and human microbiota: A review of the science.}, journal = {Experimental eye research}, volume = {245}, number = {}, pages = {109951}, pmid = {38838972}, issn = {1096-0007}, support = {U01 EY034686/EY/NEI NIH HHS/United States ; P30 EY014801/EY/NEI NIH HHS/United States ; R01 EY030851/EY/NEI NIH HHS/United States ; I01 CX002015/CX/CSRD VA/United States ; U24 EY035102/EY/NEI NIH HHS/United States ; R01 EY034718/EY/NEI NIH HHS/United States ; I01 BX004893/BX/BLRD VA/United States ; I21 RX003883/RX/RRD VA/United States ; R33 EY032468/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Dry Eye Syndromes/microbiology ; *Microbiota/physiology ; *Dysbiosis ; *Gastrointestinal Microbiome/physiology ; Tears/metabolism ; Mouth/microbiology ; }, abstract = {A complex relationship exists between human microbiota and the risk for ophthalmic disease. While the homeostatic composition of human microbiota is still being established, including what defines dysbiosis (i.e. changes in diversity and abundance), pilot research has begun to identify the potential influence of demographics, geography, and co-morbidities on the microbiota and describe their impact on ocular health. This review specifically focuses on the scientific relationships of the human oral and gut microbiota to dry eye disease (DED), a set of conditions impacting the tear film and ocular surface. Although data are sparse and often conflict across studies, the literature generally supports associations between microbial imbalance (dysbiosis) and DED and alterations in microbial diversity and abundance to specific aspects of DED. This review examines the relevant science and mechanistic relationships linking gut and oral dysbiosis and DED. Various physiochemical factors and therapeutic approaches that alter microbiota, including medications and fecal transplants are examined in relation to DED.}, }
@article {pmid38838927, year = {2024}, author = {Meng, Y and Sun, J and Zhang, G}, title = {A viable remedy for overcoming resistance to anti-PD-1 immunotherapy: Fecal microbiota transplantation.}, journal = {Critical reviews in oncology/hematology}, volume = {200}, number = {}, pages = {104403}, doi = {10.1016/j.critrevonc.2024.104403}, pmid = {38838927}, issn = {1879-0461}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Immunotherapy/methods ; *Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; Neoplasms/therapy/immunology ; Gastrointestinal Microbiome/immunology ; Drug Resistance, Neoplasm ; Animals ; }, abstract = {Anti-PD-1 immunotherapy is a cancer therapy that focuses explicitly on the PD-1 receptor found on the surface of immune cells. This targeted therapeutic strategy is specifically designed to amplify the immune system's innate capacity to detect and subsequently eliminate cells that have become cancerous. Nevertheless, it should be noted that not all patients exhibit a favourable response to this particular therapeutic modality, necessitating the exploration of novel strategies to augment the effectiveness of immunotherapy. Previous studies have shown that fecal microbiota transplantation (FMT) can enhance the efficacy of anti-PD-1 immunotherapy in advanced melanoma patients. To investigate this intriguing possibility further, we turned to PubMed and conducted a comprehensive search for studies that analyzed the interplay between FMT and anti-PD-1 therapy in the context of tumor treatment. Our search criteria were centred around two key phrases: "fecal microbiota transplantation" and "anti-PD-1 therapy." The studies we uncovered all echo a similar sentiment. They pointed towards the potential of FMT to improve the effectiveness of immunotherapy. FMT may enhance the effectiveness of immunotherapy by altering the gut microbiota and boosting the patient's immunological response. Although promising, additional investigation is needed to improve the efficacy of FMT in the context of cancer therapy and attain a comprehensive understanding of the possible advantages and drawbacks associated with this therapeutic strategy.}, }
@article {pmid38838871, year = {2024}, author = {Chen, X and Mo, X and Zhang, Y and He, D and Xiao, R and Cheng, Q and Wang, H and Liu, L and Li, WW and Xie, P}, title = {A comprehensive analysis of the differential expression in the hippocampus of depression induced by gut microbiota compared to traditional stress.}, journal = {Gene}, volume = {927}, number = {}, pages = {148633}, doi = {10.1016/j.gene.2024.148633}, pmid = {38838871}, issn = {1879-0038}, mesh = {*Gastrointestinal Microbiome ; Animals ; *Hippocampus/metabolism ; Mice ; *Stress, Psychological ; *Fecal Microbiota Transplantation ; Male ; *Depressive Disorder, Major/microbiology/metabolism ; Humans ; Disease Models, Animal ; Depression ; Mice, Inbred C57BL ; Dysbiosis/microbiology ; Gene Expression Profiling/methods ; }, abstract = {Depression, which is a disease of heterogeneous etiology, is characterized by high disability and mortality rates. Gut microbiota are associated with the development of depression. To further explore any differences in the mechanisms of depression induced by gut microbiota and traditional stresses, as well as facilitate the development of microbiota-based interventions, a fecal microbiota transplantation (FMT) depression model was made. This was achieved by transplanting feces from major depressive disorder (MDD) patients into germ-free mice. Second, the mechanisms of the depression induced by gut microbiota were analyzed in comparison with those of the depression caused by different forms of stress. It turned out that mice exhibited depressive-like behavior after FMT. Then, PCR array analysis was performed on the hippocampus of the depressed mice to identify differentially expressed genes (DEGs). The KEGG analysis revealed that the pathways of depression induced by gut microbes are closely associated with immuno-inflammation. To determine the pathogenic pathways of physiological stress and psychological stress-induced depression, raw data was extracted from several databases and KEGG analysis was performed. The results from the analysis revealed that the mechanisms of depression induced by physiological and psychological stress are closely related to the regulation of neurotransmitters and energy metabolism. Interestingly, the immunoinflammatory response was distinct across different etiologies that induced depression. The findings showed that gut microbiota dysbiosis-induced depression was mainly associated with adaptive immunity, while physiological stress-induced depression was more linked to innate immunity. This study compared the pathogenesis of depression caused by gut microbiota dysbiosis, and physiological and psychological stress. We explored new intervention methods for depression and laid the foundation for precise treatment.}, }
@article {pmid38838169, year = {2024}, author = {Han, M and Liang, J and Hou, M and Liu, Y and Li, H and Gao, Z}, title = {Bifidobacterium bifidum Ameliorates DSS-Induced Colitis in Mice by Regulating Microbial Metabolome and Targeting Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c00365}, pmid = {38838169}, issn = {1520-5118}, abstract = {Inflammatory bowel disease (IBD) is a recurrent inflammatory condition affecting the gastrointestinal tract, and its clinical treatment remains suboptimal. Probiotics have shown effectiveness in alleviating dextran sulfate sodium salt (DSS)-induced colitis, exhibiting strain-specific anti-inflammatory properties. In this study, we compared the therapeutic effects of five strains of Bifidobacterium bifidum isolated from healthy adult feces on DSS-induced colitis in mice. Additionally, we investigated the underlying mechanisms by examining gut microbiota composition and microbial metabolome. Our findings highlighted the superior efficacy of B. bifidum M1-3 compared to other strains. It significantly improved colitis symptoms, mitigated gut barrier disruption, and reduced colonic inflammation in DSS-treated mice. Moreover, gut microbiota composition analysis revealed that B. bifidum M1-3 treatment increased the abundance and diversity of gut microbiota. Specifically, it significantly increased the abundance of Muribaculaceae, Lactobacillus, Bacteroides, and Enterorhabdus, while decreasing the abundance of Escherichia-Shigella. Furthermore, our nontargeted metabolomics analysis illustrated that B. bifidum M1-3 treatment had a regulatory effect on various metabolic pathways, including tyrosine metabolism, lysine degradation, and tryptophan metabolism. Importantly, we confirmed that the therapeutic efficiency of B. bifidum M1-3 was dependent on the gut microbiota. These results are conducive to the development of probiotic products for alleviating colitis.}, }
@article {pmid38835159, year = {2024}, author = {Lyu, W and Li, DF and Li, SY and Hu, H and Zhou, JY and Wang, L}, title = {Gut microbiota modulation: a narrative review on a novel strategy for prevention and alleviation of ovarian aging.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/10408398.2024.2361306}, pmid = {38835159}, issn = {1549-7852}, abstract = {The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.}, }
@article {pmid38835057, year = {2024}, author = {Gu, N and Yan, J and Tang, W and Zhang, Z and Wang, L and Li, Z and Wang, Y and Zhu, Y and Tang, S and Zhong, J and Cheng, C and Sun, X and Huang, Z}, title = {Prevotella copri transplantation promotes neurorehabilitation in a mouse model of traumatic brain injury.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {147}, pmid = {38835057}, issn = {1742-2094}, support = {82172193//National Natural Science Foundation of China/ ; 82071397//National Natural Science Foundation of China/ ; 82102316//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Brain Injuries, Traumatic ; Mice ; Male ; *Mice, Inbred C57BL ; *Disease Models, Animal ; Neurological Rehabilitation/methods ; Prevotella ; Gastrointestinal Microbiome/physiology ; Phosphatidylinositol 3-Kinases/metabolism ; }, abstract = {BACKGROUND: The gut microbiota plays a critical role in regulating brain function through the microbiome-gut-brain axis (MGBA). Dysbiosis of the gut microbiota is associated with neurological impairment in Traumatic brain injury (TBI) patients. Our previous study found that TBI results in a decrease in the abundance of Prevotella copri (P. copri). P. copri has been shown to have antioxidant effects in various diseases. Meanwhile, guanosine (GUO) is a metabolite of intestinal microbiota that can alleviate oxidative stress after TBI by activating the PI3K/Akt pathway. In this study, we investigated the effect of P. copri transplantation on TBI and its relationship with GUO-PI3K/Akt pathway.<br><br>METHODS: In this study, a controlled cortical impact (CCI) model was used to induce TBI in adult male C57BL/6J mice. Subsequently, P. copri was transplanted by intragastric gavage for 7 consecutive days. To investigate the effect of the GUO-PI3K/Akt pathway in P. copri transplantation therapy, guanosine (GUO) was administered 2&#xa0;h after TBI for 7 consecutive days, and PI3K inhibitor (LY294002) was administered 30&#xa0;min before TBI. Various techniques were used to assess the effects of these interventions, including quantitative PCR, neurological behavior tests, metabolite analysis, ELISA, Western blot analysis, immunofluorescence, Evans blue assays, transmission electron microscopy, FITC-dextran permeability assay, gastrointestinal transit assessment, and 16&#xa0;S rDNA sequencing.<br><br>RESULTS: P. copri abundance was significantly reduced after TBI. P. copri transplantation alleviated motor and cognitive deficits tested by the NSS, Morris's water maze and open field test. P. copri transplantation attenuated oxidative stress and blood-brain barrier damage and reduced neuronal apoptosis after TBI. In addition, P. copri transplantation resulted in the reshaping of the intestinal flora, improved gastrointestinal motility and intestinal permeability. Metabolomics and ELISA analysis revealed a significant increase in GUO levels in feces, serum and injured brain after P. copri transplantation. Furthermore, the expression of p-PI3K and p-Akt was found to be increased after P. copri transplantation and GUO treatment. Notably, PI3K inhibitor LY294002 treatment attenuated the observed improvements.<br><br>CONCLUSIONS: We demonstrate for the first time that P. copri transplantation can improve GI functions and alter gut microbiota dysbiosis after TBI. Additionally, P. copri transplantation can ameliorate neurological deficits, possibly via the GUO-PI3K/Akt signaling pathway after TBI.}, }
@article {pmid38834146, year = {2024}, author = {Dafnis, G}, title = {Transsphincteric Repair of Rectourethral Fistulas in Combination With Dartos Muscle Flap Interposition Following Radical Prostatectomy.}, journal = {Urology}, volume = {191}, number = {}, pages = {130-135}, doi = {10.1016/j.urology.2024.05.041}, pmid = {38834146}, issn = {1527-9995}, mesh = {Humans ; Male ; *Rectal Fistula/surgery/etiology ; *Prostatectomy/methods/adverse effects ; *Urinary Fistula/surgery/etiology ; *Urethral Diseases/surgery/etiology ; *Surgical Flaps/transplantation ; Middle Aged ; Aged ; Scrotum/surgery ; Urologic Surgical Procedures, Male/methods ; Postoperative Complications/etiology/surgery ; Retrospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVE: To present our experience with a novel technique that combines the York-Mason transsphincteric approach with dartos muscle flap interposition to treat rectourethral fistulas.<br><br>METHODS: We extracted records from our prospectively kept database of 35 procedures conducted for treating rectourethral fistulas during 2002-2023; the York-Mason approach was combined with dartos muscle flap interposition in 5 cases, performed for treating rectourethral fistulas due to radical prostatectomy, all of which were referral cases.<br><br>RESULTS: All 5 patients were successfully treated and followed up for a median of 70.0&#xa0;months without recurrence. Before the fistula repair, all had a diverting stoma. In all cases, the first voiding cystourethrogram revealed a healed fistula. The posterior and the scrotal incisions healed uneventfully. All patients reported normal voiding and no urinary incontinence. To date, the stoma has closed in 3 patients, all of whom had intact fecal continence and no postoperative anal stenosis.<br><br>CONCLUSION: The transsphincteric modified York-Mason approach combined with dartos muscle flap interposition resulted in complete healing of rectourethral fistulas.}, }
@article {pmid38833830, year = {2024}, author = {Ma, B and Wang, D and Chen, X and Wang, Q and Zhang, T and Wen, R and Yang, M and Li, C and Lei, C and Wang, H}, title = {Dietary α-linolenic acid supplementation enhances resistance to Salmonella Typhimurium challenge in chickens by altering the intestinal mucosal barrier integrity and cecal microbes.}, journal = {Microbiological research}, volume = {285}, number = {}, pages = {127773}, doi = {10.1016/j.micres.2024.127773}, pmid = {38833830}, issn = {1618-0623}, mesh = {Animals ; *Chickens/microbiology ; *Salmonella typhimurium/drug effects ; *Dietary Supplements ; *Gastrointestinal Microbiome/drug effects ; *alpha-Linolenic Acid/pharmacology/administration &amp; dosage ; *Salmonella Infections, Animal/prevention &amp; control/microbiology ; *Poultry Diseases/microbiology/prevention &amp; control ; *Intestinal Mucosa/microbiology ; *Cecum/microbiology ; Animal Feed ; Fecal Microbiota Transplantation ; }, abstract = {Salmonella is an important foodborne pathogen. Given the ban on the use of antibiotics during the egg-laying period in China, finding safe and effective alternatives to antibiotics to reduce Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infections in chickens is essential for the prevention and control of this pathogen and the protection of human health. Numerous studies have shown that unsaturated fatty acids have a positive effect on intestinal inflammation and resistance to infection by intestinal pathogens. Here we investigated the protective effect of α-linolenic acid (ALA) against S. Typhimurium infection in chickens and further explored its mechanism of action. We added different proportions of ALA to the feed and observed the effect of ALA on S. Typhimurium colonization using metagenomic sequencing technology and physiological index measurements. The role of gut flora on S. Typhimurium colonization was subsequently verified by fecal microbiota transplantation (FMT). We found that ALA protects chickens from S. Typhimurium infection by reducing intestinal inflammation through remodeling the gut microbiota, up-regulating the expression of ileocecal barrier-related genes, and maintaining the integrity of the intestinal epithelium. Our data suggest that supplementation of feed with ALA may be an effective strategy to alleviate S. Typhimurium infection in chickens.}, }
@article {pmid38831430, year = {2024}, author = {Gao, X and Zhu, Z and Bao, Y and Li, Y and Zhu, W and He, X and Ge, X and Huang, W and Wang, H and Wei, W and Du, J and Chen, L and Li, H and Sheng, L}, title = {Chrysanthemum morifolium Ramat extract and probiotics combination ameliorates metabolic disorders through regulating gut microbiota and PPARα subcellular localization.}, journal = {Chinese medicine}, volume = {19}, number = {1}, pages = {76}, pmid = {38831430}, issn = {1749-8546}, support = {82273624//National Natural Science Foundation of China/ ; U21A20413//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Chrysanthemum morifolium Ramat, a traditional Chinese medicine, has the effects on liver clearing, vision improving, and anti-inflammation. C. morifolium and probiotics have been individually studied for their beneficial effects on metabolic diseases. However, the underlying molecular mechanisms were not completely elucidated. This study aims to elucidate the potential molecular mechanisms of C. morifolium and probiotics combination (CP) on alleviating nonalcoholic fatty liver disease (NAFLD) and the dysregulation of glucose metabolism in high-fat diet (HFD)-fed mice.<br><br>METHODS: The therapeutic effect of CP on metabolism was evaluated by liver histology and serum biochemical analysis, as well as glucose tolerance test. The impact of CP on gut microbiota was analyzed by 16S rRNA sequencing and fecal microbiota transplantation. Hepatic transcriptomic analysis was performed with the key genes and proteins validated by RT-qPCR and western blotting. In addition, whole body Ppar&#x3b1; knockout (Ppar&#x3b1;[-/-]) mice were used to confirm the CP-mediated pathway.<br><br>RESULTS: CP supplementation ameliorated metabolic disorders by reducing body weight and hepatic steatosis, and improving glucose intolerance and insulin resistance in HFD fed mice. CP intervention mitigated the HFD-induced gut microbiota dysbiosis, which contributed at least in part, to the beneficial effect of improving glucose metabolism. In addition, hepatic transcriptomic analysis showed that CP modulated the expression of genes associated with lipid metabolism. CP downregulated the mRNA level of lipid droplet-binding proteins, such as Cidea and Cidec in the liver, leading to more substrates for fatty acid oxidation (FAO). Meanwhile, the expression of CPT1&#x3b1;, the rate-limiting enzyme of FAO, was significantly increased upon CP treatment. Mechanistically, though CP didn't affect the total PPAR&#x3b1; level, it promoted the nuclear localization of PPAR&#x3b1;, which contributed to the reduced expression of Cidea and Cidec, and increased expression of CPT1&#x3b1;, leading to activated FAO. Moreover, whole body PPAR&#x3b1; deficiency abolished the anti-NAFLD effect of CP, suggesting the importance of PPAR&#x3b1; in CP-mediated beneficial effect.<br><br>CONCLUSION: This study revealed the hypoglycemic and hepatoprotective effect of CP by regulating gut microbiota composition and PPAR&#x3b1; subcellular localization, highlighting its potential for therapeutic candidate for metabolic disorders.}, }
@article {pmid38831225, year = {2024}, author = {Raghani, N and Postwala, H and Shah, Y and Chorawala, M and Parekh, P}, title = {From Gut to Brain: Unraveling the Intricate Link Between Microbiome and Stroke.}, journal = {Probiotics and antimicrobial proteins}, volume = {16}, number = {6}, pages = {2039-2053}, pmid = {38831225}, issn = {1867-1314}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Stroke/prevention &amp; control ; *Brain-Gut Axis/physiology ; Animals ; Brain ; Probiotics/administration &amp; dosage ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Fatty Acids, Volatile/metabolism ; }, abstract = {Stroke, a neurological disorder, is intricately linked to the gut microbiota, influencing microbial composition and elevating the risk of ischemic stroke. The neuroprotective impact of short-chain fatty acids (SCFAs) derived from dietary fiber fermentation contrasts with the neuroinflammatory effects of lipopolysaccharide (LPS) from gut bacteria. The pivotal role of the gut-brain axis, facilitating bidirectional communication between the gut and the brain, is crucial in maintaining gastrointestinal equilibrium and influencing cognitive functions. An in-depth understanding of the interplay among the gut microbiota, immune system, and neurological outcomes in stroke is imperative for devising innovative preventive and therapeutic approaches. Strategies such as dietary adjustments, probiotics, prebiotics, antibiotics, or fecal transplantation offer promise in modulating stroke outcomes. Nevertheless, comprehensive research is essential to unravel the precise mechanisms governing the gut microbiota's involvement in stroke and to establish effective therapeutic interventions. The initiation of large-scale clinical trials is warranted to assess the safety and efficacy of interventions targeting the gut microbiota in stroke management. Tailored strategies that reinstate eubiosis and foster a healthy gut microbiota hold potential for both stroke prevention and treatment. This review underscores the gut microbiota as a promising therapeutic target in stroke and underscores the need for continued research to delineate its precise role and develop microbiome-based interventions effectively.}, }
@article {pmid38830845, year = {2024}, author = {Mao, X and Larsen, SB and Zachariassen, LSF and Brunse, A and Adamberg, S and Mejia, JLC and Larsen, F and Adamberg, K and Nielsen, DS and Hansen, AK and Hansen, CHF and Rasmussen, TS}, title = {Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4704}, pmid = {38830845}, issn = {2041-1723}, support = {R324-2019-1880//Lundbeckfonden (Lundbeck Foundation)/ ; NNF-20OC0063874//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; }, mesh = {Animals ; Male ; *Metabolic Syndrome/therapy ; *Obesity/therapy ; *Gastrointestinal Microbiome ; *Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; Mice ; *Diet, High-Fat/adverse effects ; *Virome ; *Mice, Obese ; Dysbiosis/therapy ; Feces/virology/microbiology ; Bacteriophages/physiology ; Blood Glucose/metabolism ; Disease Models, Animal ; Liver/pathology/metabolism ; Adipose Tissue ; }, abstract = {Metabolic syndrome encompasses amongst other conditions like obesity and type-2 diabetes and is associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM; however, concerns on accidentally transferring pathogenic microbes remain. As a safer alternative, fecal virome transplantation (FVT, sterile-filtrated feces) has the advantage over FMT in that mainly bacteriophages are transferred. FVT from lean male donors have shown promise in alleviating the metabolic effects of high-fat diet in a preclinical mouse study. However, FVT still carries the risk of eukaryotic viral infections. To address this, recently developed methods are applied for removing or inactivating eukaryotic viruses in the viral component of FVT. Modified FVTs are compared with unmodified FVT and saline in a diet-induced obesity model on male C57BL/6 N mice. Contrasted with obese control, mice administered a modified FVT (nearly depleted for eukaryotic viruses) exhibits enhanced blood glucose clearance but not weight loss. The unmodified FVT improves liver pathology and reduces the proportions of immune cells in the adipose tissue with a non-uniform response. GM analysis suggests that bacteriophage-mediated GM modulation influences outcomes. Optimizing these approaches could lead to the development of safe bacteriophage-based therapies targeting metabolic syndrome through GM restoration.}, }
@article {pmid38829940, year = {2024}, author = {Tan, S and Zhang, W and Zeng, P and Yang, Y and Chen, S and Li, Y and Bian, Y and Xu, C}, title = {Clinical effects of chemical drugs, fecal microbiota transplantation, probiotics, dietary fiber, and acupuncture in the treatment of chronic functional constipation: a systematic review and network meta-analysis.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {36}, number = {7}, pages = {815-830}, doi = {10.1097/MEG.0000000000002786}, pmid = {38829940}, issn = {1473-5687}, mesh = {*Constipation/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/adverse effects ; *Dietary Fiber/therapeutic use ; *Probiotics/therapeutic use/adverse effects ; Chronic Disease ; *Acupuncture Therapy/methods ; Treatment Outcome ; Network Meta-Analysis ; Randomized Controlled Trials as Topic ; Quality of Life ; Laxatives/therapeutic use ; }, abstract = {Currently, there are increasingly diverse treatment modalities for chronic functional constipation (CFC). This study aims to compare the relative efficacy and safety of chemical drugs, fecal microbiota transplantation (FMT), probiotics, dietary fiber, and acupuncture in the treatment of patients with CFC. We searched relevant randomized controlled trials (RCTs) published in five databases up to November 2023. Network meta-analysis (NMA) was carried out using R Studio 4.2.1. Cumulative ranking probability plots, assessed through the surface under the cumulative ranking (SUCRA), were employed to rank the included drugs for various outcome measures. We included a total of 45 RCT studies with 17 118 patients with CFC. From the SUCRA values and NMA results FMT showed the best utility in terms of clinical efficacy, Bristol stool form scale scores, patient assessment of constipation quality of life scores, and the treatment modality with the lowest ranked incidence of adverse effects was electroacupuncture. Subgroup analysis of the chemotherapy group showed that sodium A subgroup analysis of the chemical group showed that sodium picosulfate 10 mg had the highest clinical efficacy. FMT is more promising in the treatment of CFC and may be more effective in combination with the relatively safe treatment of acupuncture.}, }
@article {pmid38828853, year = {2024}, author = {Chasov, V and Zmievskaya, E and Ganeeva, I and Gilyazova, E and Davletshin, D and Filimonova, M and Valiullina, A and Kudriaeva, A and Bulatov, E}, title = {Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation.}, journal = {Journal of biomedical research}, volume = {38}, number = {6}, pages = {1-16}, pmid = {38828853}, issn = {1674-8301}, abstract = {Systemic lupus erythematosus (SLE) is characterized by a systemic dysfunction of the innate and adaptive immune systems, leading to an attack on healthy tissues of the body. During the development of SLE, pathogenic features, such as the formation of autoantibodies to self-nuclear antigens, caused tissue damage including necrosis and fibrosis, with an increased expression of type Ⅰ interferon (IFN) regulated genes. Treatment of lupus with immunosuppressants and glucocorticoids, which are used as the standard therapy, is not effective enough and causes side effects. As an alternative, more effective immunotherapies have been developed, including monoclonal and bispecific antibodies that target B cells, T cells, co-stimulatory molecules, cytokines or their receptors, and signaling molecules. Encouraging results have been observed in clinical trials with some of these therapies. Furthermore, a chimeric antigen receptor T cells (CAR-T) therapy has emerged as the most effective, safe, and promising treatment option for SLE, as demonstrated by successful pilot studies. Additionally, emerging evidence suggests that gut microbiota dysbiosis may play a significant role in the severity of SLE, and the use of methods to normalize the gut microbiota, particularly fecal microbiota transplantation (FMT), opens up new opportunities for effective treatment of SLE.}, }
@article {pmid38828210, year = {2024}, author = {Ravel, SJ and Hollifield, VM}, title = {Fecal Microbiota Transplantation in a Domestic Ferret Suffering from Chronic Diarrhea and Maldigestion-Fecal Microbiota and Clinical Outcome: A Case Report.}, journal = {Veterinary medicine (Auckland, N.Z.)}, volume = {15}, number = {}, pages = {171-180}, pmid = {38828210}, issn = {2230-2034}, abstract = {This case report describes the effects of fecal microbiota transplantation (FMT) administered via enema in a 4-year-old spayed, champagne Domestic Ferret (Mustela putorius furo) with chronic diarrhea, maldigestion and weight loss. We aimed to establish a protocol for FMT as a novel therapeutic treatment for chronic diarrhea in domestic ferrets. We mapped the fecal microbiome by 16S rRNA gene amplicon sequencing to track the patient's fecal microbiota throughout the treatment and observation period. Initial oral FMTs were associated with temporary weight improvement but subsequent treatments, via enema and oral delivery, showed varied outcomes. Molecular analysis highlighted distinct gut microbiota composition profiles between the healthy donor and the diseased ferret. The diseased ferret initially exhibited high abundance of Enterobacteriaceae, Escherichia, and Enterobacter, which ultimately normalized to level like those found in the donor ferret. Overall, the gut microbiota of the recipient became more similar to the donor microbiota using a Yue-Clayton theta coefficients analysis. After a restoration of the gut microbiota and clinical improvement, the recipient's symptoms returned indicating that repeated FMTs might be required for long-term resolution of symptoms and complete restructuring of the gut microbiota. Future studies are warranted to map the microbiome of a larger population of domestic ferrets to investigate a potential correlation between fecal microbiota profiles and chronic/acute gastrointestinal disorders.}, }
@article {pmid38826830, year = {2024}, author = {Sahle, Z and Engidaye, G and Shenkute Gebreyes, D and Adenew, B and Abebe, TA}, title = {Fecal microbiota transplantation and next-generation therapies: A review on targeting dysbiosis in metabolic disorders and beyond.}, journal = {SAGE open medicine}, volume = {12}, number = {}, pages = {20503121241257486}, pmid = {38826830}, issn = {2050-3121}, abstract = {The human microbiome, particularly the gut microbiome, has emerged as a central determinant of health and disease. Dysbiosis, an imbalance in the microbial composition of the gut, is associated with a variety of metabolic and other diseases, highlighting the potential for microbiota-targeted treatments. Fecal microbiota transplantation has received considerable attention as a promising therapy to modulate the gut microbiome and restore microbial homeostasis. However, challenges remain, including standardization, safety, and long-term efficacy. This review summarizes current knowledge on fecal microbiota transplantation and describes the next generation therapies targeting microbiome. This review looked at the mechanistic understanding of fecal microbiota transplantation and alternative strategies, elucidating their potential role in improving dysbiosis-associated metabolic disorders, such as obesity, and type 2 diabetes and others. Additionally, this review discussed the growing application of therapies targeting the gut microbiome. Insights from clinical trials, preclinical studies, and emerging technologies provide a comprehensive overview of the evolving landscape of microbiome-based interventions. Through a critical assessment of current advances and prospects, this review aims to highlight the therapeutic potential of targeting gut microbiome and pave the way for innovative approaches in precision medicine and personalized treatments.}, }
@article {pmid38825293, year = {2024}, author = {Wu, L and Hu, Z and Lv, Y and Ge, C and Luo, X and Zhan, S and Huang, W and Shen, X and Yu, D and Liu, B}, title = {Hericium erinaceus polysaccharides ameliorate nonalcoholic fatty liver disease via gut microbiota and tryptophan metabolism regulation in an aged laying hen model.}, journal = {International journal of biological macromolecules}, volume = {273}, number = {Pt 1}, pages = {132735}, doi = {10.1016/j.ijbiomac.2024.132735}, pmid = {38825293}, issn = {1879-0003}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Tryptophan/metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism/drug therapy ; *Chickens ; *Polysaccharides/pharmacology/chemistry ; *Disease Models, Animal ; Female ; Liver/metabolism/drug effects/pathology ; }, abstract = {Polysaccharides extracted from Hericium erinaceus (HEP) exhibit hepatoprotective activity in the alleviation of non-alcoholic fatty liver disease (NAFLD); however, the mechanisms underlying whether and how HEP regulation of the gut microbiota to alleviate liver-associated metabolic disorders are not well understood. This study used an aged laying hen model to explore the mechanisms through which HEP alleviates NAFLD, with a focus on regulatory function of HEP in the gut microbiome. The results showed that HEP ameliorated hepatic damage and metabolic disorders by improving intestinal barrier function and shaping the gut microbiota and tryptophan metabolic profiles. HEP increased the abundance of Lactobacillus and certain tryptophan metabolites, including indole-3-carboxylic acid, kynurenic acid, and tryptamine in the cecum. These metabolites upregulated the expression of ZO-1 and Occludin by activating the AhR and restoring the intestinal barrier integrity. The increased intestinal barrier functions decreased LPS transferring from the intestine to the liver, inhibited hepatic LPS/TLR4/MyD88/NF-κB pathway activation, and reduced hepatic inflammatory response and apoptosis. Fecal microbiota transplantation experiments further confirmed that the hepatoprotective effect is likely mediated by HEP-altered gut microbiota and their metabolites. Overall, dietary HEP could ameliorate the hepatic damage and metabolic disorders of NAFLD through regulating the "gut-liver" axis.}, }
@article {pmid38824460, year = {2024}, author = {He, Z and Liu, Y and Li, Z and Sun, T and Li, Z and Liu, C and Xiang, H}, title = {Gut Microbiota-Mediated Alterations of Hippocampal CB1R Regulating the Diurnal Variation of Cognitive Impairment Induced by Hepatic Ischemia-Reperfusion Injury in Mice.}, journal = {Neurochemical research}, volume = {49}, number = {8}, pages = {2165-2178}, pmid = {38824460}, issn = {1573-6903}, support = {82070302//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Male ; Mice ; Circadian Rhythm/physiology ; *Cognitive Dysfunction/metabolism/etiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; *Hippocampus/metabolism ; Liver/metabolism ; Maze Learning/physiology ; Mice, Inbred C57BL ; *Receptor, Cannabinoid, CB1/metabolism ; *Reperfusion Injury/metabolism ; }, abstract = {Patients suffering from hepatic ischemia-reperfusion injury (HIRI) frequently exhibit postoperative cognitive deficits. Our previous observations have emphasized the diurnal variation in hepatic ischemia-reperfusion injury-induced cognitive impairment, in which gut microbiota-associated hippocampal lipid metabolism plays an important role. Herein, we further investigated the molecular mechanisms involved in the process. Hepatic ischemia-reperfusion surgery was performed under morning (ZT0, 08:00) and evening (ZT12, 20:00). Fecal microbiota transplantation was used to associate HIRI model with pseudo-germ-free mice. The novel object recognition test and Y-maze test were used to assess cognitive function. 16S rRNA gene sequencing and analysis were used for microbial analysis. Western blotting was used for hippocampal protein analysis. Compared with the ZT0-HIRI group, ZT12-HIRI mice showed learning and short term memory impairment, accompanied by down-regulated expression of hippocampal CB1R, but not CB2R. Both gut microbiota composition and microbiota metabolites were significantly different in ZT12-HIRI mice compared with ZT0-HIRI. Fecal microbiota transplantation from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior and down-regulated hippocampal CB1R and β-arrestin1. Intraperitoneal administration of CB1R inhibitor AM251 (1 mg/kg) down-regulated hippocampal CB1R and caused cognitive impairment in ZT0-HIRI mice. And intraperitoneal administration of CB1R agonist WIN 55,212-2 (1 mg/kg) up-regulated hippocampal CB1R and improved cognitive impairment in ZT12-HIRI mice. In summary, the results suggest that gut microbiota may regulate the diurnal variation of HIRI-induced cognitive function by interfering with hippocampal CB1R.}, }
@article {pmid38823462, year = {2024}, author = {Xu, H and Li, O and Kim, D and Xue, M and Bao, Z and Yang, F}, title = {Aged microbiota exacerbates cardiac failure by PPARα/PGC1α pathway.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1870}, number = {7}, pages = {167271}, doi = {10.1016/j.bbadis.2024.167271}, pmid = {38823462}, issn = {1879-260X}, mesh = {*PPAR alpha/metabolism ; *Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism/genetics ; Animals ; *Heart Failure/microbiology/metabolism/pathology/therapy ; Mice ; *Gastrointestinal Microbiome ; *Signal Transduction ; Male ; *Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Aging/metabolism ; Humans ; Disease Models, Animal ; }, abstract = {The dysbiosis of gut microbiota with aging has been extensively studied, revealing its substantial contribution to variety of diseases. However, the impact of aged microbiota in heart failure (HF) remains unclear. In this study, we employed the method of fecal microbiota transplantation (FMT) from aged donors to investigate its role in the context of HF. Our results demonstrate that FMT from aged donors alters the recipient's gut microbiota composition and abundance. Furthermore, FMT impairs cardiac function and physical activity in HF mice. Aged FMT induces metabolic alterations, leading to body weight gain, impaired glucose tolerance, increased respiratory exchange ratio, and enhanced fat accumulation. The epicardium of aged FMT recipients shows fat accumulation, accompanied by cardiomyocyte hypertrophy, cardiac fibrosis and increased cellular apoptosis. Mechanistically, aged FMT suppresses the PPARα/PGC1α signaling pathway in HF. Notably, activation of PPARα effectively rescues the metabolic changes and myocardial injury caused by aged FMT. In conclusion, our study emphasizes the role of the PPARα/PGC1α signaling pathway in aged FMT-mediated HF.}, }
@article {pmid38821245, year = {2024}, author = {Huang, Y and Li, Y and Guan, D and Pan, Y and Yang, C and Liu, H and Chen, C and Chen, W and Liu, J and Wan, T and Zhuang, L and Wang, Q and Zhang, Y}, title = {Acorus tatarinowii oils exert protective effects on microglia-mediated inflammatory injury via restoring gut microbiota composition in experimental stroke rats.}, journal = {Brain research bulletin}, volume = {213}, number = {}, pages = {110990}, doi = {10.1016/j.brainresbull.2024.110990}, pmid = {38821245}, issn = {1873-2747}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Microglia/drug effects/metabolism ; Rats ; Male ; *Acorus/chemistry ; *Rats, Sprague-Dawley ; Neuroprotective Agents/pharmacology ; Neuroinflammatory Diseases/drug therapy/metabolism ; Stroke/drug therapy ; Infarction, Middle Cerebral Artery ; Plant Oils/pharmacology ; Disease Models, Animal ; Inflammation/drug therapy ; }, abstract = {Growing evidence has demonstrated that gut microbiota could be developed as a therapeutic target due to its contribution to microglia activation in the pathological process of ischemic stroke. Acorus tatarinowii oils (AT oils), which is considered as the active fraction of a traditional Chinese herbal medicine Acorus tatarinowii, exerts various bioactivities and prebiotic effects. However, it remains unclear that the effect of AT oils on inflammatory response after ischemic stroke and whether its underlying mechanism is associated to gut microbiota and the intestinal barrier. In the current study, we aim to investigate the anti-microglial neuroinflammation mechanism of AT oils in a middle cerebral artery occlusion model of ischemic stroke. The compositions of AT oils were identified by GC-MS. Our results demonstrated that AT oils could effectively relieve cerebral infarction, inhibit neuronal apoptosis, degrade the release of pro-inflammatory factors (TNF-α, IL-17, IL-6 and IFN-γ), and mediate the polarization of microglia. Moreover, AT oils restored the composition and the balance of gut microbiota in stroke rats, and reduced abundance of opportunistic genera including Verrucomicrobia, Akkermansia and Tenericutes, as well as increased beneficial bacteria abundance such as Tenericutes and Prevotella_copri. To investigate the role of gut microbiota on AT oils against ischemic stroke, we conducted the fecal microbiota transplantation (FMT) experiments with gut microbiota consumption, which suggested that the depletion of gut microbiota took away the protective effect of AT oils, confirming the importance of gut microbiota in the protective effect of AT oils on ischemic stroke. FMT experiments have demonstrated that AT oils preserved the gut permeability and blood-brain barrier, as well as mediated the microglial phenotype under the intervention of gut microbiota. In summary, AT oils could efficaciously moderate neuronal damage and intervene microglial phenotype by reversing gut microbiota disorder in ischemic stroke rats.}, }
@article {pmid38821056, year = {2024}, author = {Swisa, A and Kieckhaefer, J and Daniel, SG and El-Mekkoussi, H and Kolev, HM and Tigue, M and Jin, C and Assenmacher, CA and Dohnalová, L and Thaiss, CA and Karlsson, NG and Bittinger, K and Kaestner, KH}, title = {The evolutionarily ancient FOXA transcription factors shape the murine gut microbiome via control of epithelial glycosylation.}, journal = {Developmental cell}, volume = {59}, number = {16}, pages = {2069-2084.e8}, pmid = {38821056}, issn = {1878-1551}, support = {P30 DK050306/DK/NIDDK NIH HHS/United States ; R01 DK139049/DK/NIDDK NIH HHS/United States ; R01 DK053839/DK/NIDDK NIH HHS/United States ; P30 DK019525/DK/NIDDK NIH HHS/United States ; R37 DK053839/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; Glycosylation ; *Hepatocyte Nuclear Factor 3-alpha/metabolism/genetics ; *Hepatocyte Nuclear Factor 3-beta/metabolism/genetics ; *Intestinal Mucosa/metabolism/microbiology ; Mice, Inbred C57BL ; Inflammatory Bowel Diseases/microbiology/metabolism/genetics/pathology ; Dysbiosis/microbiology/metabolism/genetics ; Symbiosis ; }, abstract = {Evolutionary adaptation of multicellular organisms to a closed gut created an internal microbiome differing from that of the environment. Although the composition of the gut microbiome is impacted by diet and disease state, we hypothesized that vertebrates promote colonization by commensal bacteria through shaping of the apical surface of the intestinal epithelium. Here, we determine that the evolutionarily ancient FOXA transcription factors control the composition of the gut microbiome by establishing favorable glycosylation on the colonic epithelial surface. FOXA proteins bind to regulatory elements of a network of glycosylation enzymes, which become deregulated when Foxa1 and Foxa2 are deleted from the intestinal epithelium. As a direct consequence, microbial composition shifts dramatically, and spontaneous inflammatory bowel disease ensues. Microbiome dysbiosis was quickly reversed upon fecal transplant into wild-type mice, establishing a dominant role for the host epithelium, in part mediated by FOXA factors, in controlling symbiosis in the vertebrate holobiont.}, }
@article {pmid38820960, year = {2024}, author = {Zheng, D and Ke, X and Cai, H and Yan, C and Chen, Y and Sun, J and Chen, G}, title = {Oral administration of RDP58 ameliorated DSS-induced colitis in intestinal microbiota dependent manner.}, journal = {International immunopharmacology}, volume = {136}, number = {}, pages = {112325}, doi = {10.1016/j.intimp.2024.112325}, pmid = {38820960}, issn = {1878-1705}, mesh = {Animals ; *Dextran Sulfate ; *Gastrointestinal Microbiome/drug effects ; *Colitis/chemically induced/drug therapy/microbiology/immunology ; Administration, Oral ; *T-Lymphocytes, Regulatory/immunology ; *Mice, Inbred C57BL ; Mice ; Disease Models, Animal ; Colon/pathology/microbiology/drug effects/immunology ; Male ; Tumor Necrosis Factor-alpha/metabolism ; Fecal Microbiota Transplantation ; Humans ; Fatty Acids, Volatile/metabolism ; Oligopeptides ; }, abstract = {BACKGROUND: Although the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), has not been fully elucidated, accumulating researches suggest that intestinal microbiota imbalance contributes to the development of IBD in patients and animal models. RDP58, a peptide-based computer-assisted rational design, has been demonstrated to be effective in protecting against a wide range of autoimmune and inflammatory diseases. However, the underlying mechanism by which RDP58 protects against IBD mediated by intestinal microbiota has yet to be elucidated.<br><br>METHODS: The colitis model was induced by continuously administering 2.5&#xa0;% (wt/vol) dextran sodium sulfate (DSS) solution for 7&#xa0;days. The manifestations of colon inflammation were assessed via daily weight changes, colon length, tumor necrosis factor-alpha (TNF-&#x3b1;) level, disease activity index (DAI) score, pathology score, and intestinal barrier permeability. Intestinal microbiota analysis was carried out by 16S-rRNA sequencing. Colonic short chain fatty acids (SCFAs) and regulatory T cells (Tregs) were also detected. To further confirm the protective effect of RDP58 on intestinal microbiota, broad-spectrum antibiotic cocktail (ABX) treatment and fecal microbial transplantation (FMT) experiment were performed.<br><br>RESULTS: Oral administration of RDP58 ameliorated DSS-induced mice colitis by altering the diversity and composition of intestinal microbiota. Notably, RDP58 significantly upregulated SCFAs-producing microbiota, thereby promoting the generation of Tregs. ABX and FMT were performed to verify the above mechanism.<br><br>CONCLUSIONS: RDP58 ameliorated DSS-induced colitis through altering intestinal microbiota and enhancing SCFAs and Tregs production in intestinal microbiota dependent manner, potentially provide a novel therapy for IBD.}, }
@article {pmid38818298, year = {2024}, author = {Samanta, A and Sen Sarma, M}, title = {Fecal microbiota transplantation in the treatment of hepatic encephalopathy: A perspective.}, journal = {World journal of hepatology}, volume = {16}, number = {5}, pages = {678-683}, pmid = {38818298}, issn = {1948-5182}, abstract = {Due to its complex pathogenesis, treatment of hepatic encephalopathy (HE) continues to be a therapeutic challenge. Of late, gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use. New evidence suggests that gut microbiota plays a significant role in cerebral homeostasis. Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies. Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics, prebiotics and the latest fecal microbiota transplantation (FMT). Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE. However, questions over the appropriate dose, duration and route of administration for best treatment outcome remains unsettled.}, }
@article {pmid38818289, year = {2024}, author = {Li, Y and Zhang, XH and Wang, ZK}, title = {Microbiota treatment of functional constipation: Current status and future prospects.}, journal = {World journal of hepatology}, volume = {16}, number = {5}, pages = {776-783}, pmid = {38818289}, issn = {1948-5182}, abstract = {Functional constipation (FC) is a common disorder that is characterized by difficult stool passage, infrequent bowel movement, or both. FC is highly prevalent, recurs often, accompanies severe diseases, and affects quality of life; therefore, safe and effective therapy with long-term benefits is urgently needed. Microbiota treatment has potential value for FC treatment. Microbiota treatments include modulators such as probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). Some probiotics and prebiotics have been adopted, and the efficacy of other microbiota modulators is being explored. FMT is considered an emerging field because of its curative effects; nevertheless, substantial work must be performed before clinical implementation.}, }
@article {pmid38817661, year = {2024}, author = {Wang, L and Li, Y and Zhang, YJ and Peng, LH}, title = {Intestinal microecological transplantation for a patient with chronic radiation enteritis: A case report.}, journal = {World journal of gastroenterology}, volume = {30}, number = {19}, pages = {2603-2611}, pmid = {38817661}, issn = {2219-2840}, mesh = {Humans ; Female ; Middle Aged ; *Enteritis/microbiology/diagnosis/etiology/therapy ; *Radiation Injuries/diagnosis/microbiology/etiology/surgery ; *Gastrointestinal Microbiome/radiation effects ; *Fecal Microbiota Transplantation/methods ; *Uterine Cervical Neoplasms/radiotherapy ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; Chronic Disease ; Colonoscopy ; Intestines/microbiology/radiation effects ; Feces/microbiology ; Radiotherapy/adverse effects ; }, abstract = {BACKGROUND: The gut microbiota is strongly associated with radiation-induced gut damage. This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation enteritis.<br><br>CASE SUMMARY: A 64-year-old female with cervical cancer developed abdominal pain, diarrhea, and blood in the stool 1 year after radiotherapy. An electronic colonoscopy was performed to diagnose chronic radiation enteritis. Two courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were performed. The patient experienced short- and long-term relief from symptoms without adverse effects. Whole 16S rRNA sequencing revealed significant differences in the intestinal flora's composition between patient and healthy donors. Pathogenic bacteria, such as Escherichia fergusonii and Romboutsia timonensis, were more in the patient. Beneficial bacteria such as Faecalibacterium prausnitzii, Fusicatenibacter saccharivorans, Ruminococcus bromii, and Bifidobacterium longum were more in the healthy donors. Intestinal microbiota transplantation resulted in a significant change in the patient's intestinal flora composition. The composition converged with the donor's flora, with an increase in core beneficial intestinal bacteria, such as Eubacterium rectale, and a decrease in pathogenic bacteria. Changes in the intestinal flora corresponded with the patients' alleviating clinical symptoms.<br><br>CONCLUSION: Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal flora. This study provides a new approach for treating patients with chronic radiation enteritis.}, }
@article {pmid38816750, year = {2024}, author = {Li, Y and Sun, R and Lai, C and Liu, K and Yang, H and Peng, Z and Xu, D and Huang, F and Tang, K and Peng, Y and Liu, X}, title = {Hyperbaric oxygen therapy ameliorates intestinal and systematic inflammation by modulating dysbiosis of the gut microbiota in Crohn's disease.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {518}, pmid = {38816750}, issn = {1479-5876}, support = {82230019//National Natural Science Foundation of China/ ; 82170599//National Natural Science Foundation of China/ ; 82070651//National Natural Science Foundation of China/ ; }, mesh = {*Crohn Disease/therapy/microbiology ; Humans ; *Dysbiosis/therapy/microbiology ; *Hyperbaric Oxygenation ; *Gastrointestinal Microbiome ; Animals ; Female ; Male ; *Inflammation/therapy ; Adult ; Intestines/microbiology ; Middle Aged ; Fecal Microbiota Transplantation ; Mice ; Mice, Inbred C57BL ; Young Adult ; }, abstract = {BACKGROUND: Dysbiosis of the gut microbiota is pivotal in Crohn's disease (CD) and modulated by host physiological conditions. Hyperbaric oxygen therapy (HBOT) is a promising treatment for CD that can regulate gut microbiota. The relationship between HBOT and the gut microbiota in CD remains unknown.<br><br>METHODS: CD patients were divided into an HBOT group (n&#x2009;=&#x2009;10) and a control group (n&#x2009;=&#x2009;10) in this open-label prospective interventional study. The fecal samples before and after HBOT were used for 16&#xa0;S rRNA gene sequencing and fecal microbiota transplantation (FMT). A colitis mouse model was constructed using dextran sulfate sodium, and intestinal and systematic inflammation was evaluated. The safety and long-term effect of HBOT were observed.<br><br>RESULTS: HBOT significantly reduced the level of C-reactive protein (CRP) (80.79&#x2009;&#xb1;&#x2009;42.05&#xa0;mg/L vs. 33.32&#x2009;&#xb1;&#x2009;18.31&#xa0;mg/L, P&#x2009;=&#x2009;0.004) and the Crohn's Disease Activity Index (CDAI) (274.87&#x2009;&#xb1;&#x2009;65.54 vs. 221.54&#x2009;&#xb1;&#x2009;41.89, P&#x2009;=&#x2009;0.044). HBOT elevated the declined microbial diversity and ameliorated the altered composition of gut microbiota in patients with CD. The relative abundance of Escherichia decreased, and that of Bifidobacterium and Clostridium XIVa increased after HBOT. Mice receiving FMT from donors after HBOT had significantly less intestinal inflammation and serum CRP than the group before HBOT. HBOT was safe and well-tolerated by patients with CD. Combined with ustekinumab, more patients treated with HBOT achieved clinical response (30%vs.70%, P&#x2009;=&#x2009;0.089) and remission (20%vs.50%, P&#x2009;=&#x2009;0.160) at week 4.<br><br>CONCLUSIONS: HBOT modulates the dysbiosis of gut microbiota in CD and ameliorates intestinal and systematic inflammation. HBOT is a safe option for CD and exhibits a promising auxiliary effect to ustekinumab.<br><br>TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200061193. Registered 15 June 2022, https://www.chictr.org.cn/showproj.html?proj=171605 .}, }
@article {pmid38810793, year = {2024}, author = {Li, H and Liu, S and Chen, H and Zhou, L and Chen, B and Wang, M and Zhang, D and Han, TL and Zhang, H}, title = {Gut dysbiosis contributes to SCFAs reduction-associated adipose tissue macrophage polarization in gestational diabetes mellitus.}, journal = {Life sciences}, volume = {350}, number = {}, pages = {122744}, doi = {10.1016/j.lfs.2024.122744}, pmid = {38810793}, issn = {1879-0631}, mesh = {Animals ; *Diabetes, Gestational/metabolism/microbiology ; Female ; *Dysbiosis/metabolism ; Mice ; *Gastrointestinal Microbiome ; Pregnancy ; *Macrophages/metabolism ; *Fatty Acids, Volatile/metabolism ; *Adipose Tissue/metabolism ; Humans ; RAW 264.7 Cells ; Insulin Resistance ; Fecal Microbiota Transplantation ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; 3T3-L1 Cells ; Disease Models, Animal ; }, abstract = {AIMS: The prevalence of gestational diabetes mellitus (GDM) has spurred investigations into various interconnected factors, among which gut dysbiosis is notably prominent. Although gut dysbiosis is strongly associated with GDM, the specific role of the gut microbiome in the pathogenesis of GDM remains unknown. This study aims to explore the pathogenesis of GDM from gut microbiota.<br><br>MATERIALS AND METHODS: In our study, we constructed two GDM mice models: one induced by a high-fat diet (HFD) and the other through fecal microbiota transplantation (FMT) from GDM patients. In vitro, we used a co-culture system of RAW264.7 and 3T3-L1 adipocytes.<br><br>KEY FINDINGS: We induced a GDM-like state in pregnant mice by FMT from GDM patients, which was consistent with the HFD model. A potential mechanism identified involves the diminished abundance of SCFA-producing microbiota, which reduces SCFAs, particularly propionic acid and butyric acid. In vitro, butyric and propionic acids were observed to alleviate LPS-induced TLR4-NF-&#x3ba;B activation, thereby reducing inflammation levels and inhibiting adipose insulin resistance via the PI3K/AKT signaling pathway. This reduction appears to trigger the polarization of adipose tissue macrophages toward M1 and promote insulin resistance in adipose tissue.<br><br>SIGNIFICANCE: Our study fills this knowledge gap by finding that alterations in gut microbiota have an independent impact on hyperglycemia and insulin resistance in the GDM state. In vivo and in vitro, gut dysbiosis is linked to adipose tissue inflammation and insulin resistance via the bacterial product SCFAs in the GDM state, providing new insights into the pathogenesis of GDM.}, }
@article {pmid38810309, year = {2024}, author = {Feng, R and Wang, Q and Yu, T and Hu, H and Wu, G and Duan, X and Jiang, R and Xu, Y and Huang, Y}, title = {Quercetin ameliorates bone loss in OVX rats by modulating the intestinal flora-SCFAs-inflammatory signaling axis.}, journal = {International immunopharmacology}, volume = {136}, number = {}, pages = {112341}, doi = {10.1016/j.intimp.2024.112341}, pmid = {38810309}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Quercetin/pharmacology/therapeutic use ; Female ; *Fatty Acids, Volatile/metabolism ; Rats ; *Rats, Sprague-Dawley ; *Ovariectomy ; *Signal Transduction/drug effects ; Cytokines/metabolism ; Fecal Microbiota Transplantation ; Osteoporosis/drug therapy ; Disease Models, Animal ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; Humans ; Inflammation/drug therapy ; }, abstract = {BACKGROUND: Osteoporosis (OP) is a common systemic skeletal disorder characterized by an imbalance in bone homeostasis, involving increased osteoclastic bone formation and decreased osteoblastic bone resorption. Quercetin is a plant polyphenol that has been found to exhibit various biological activities, including antioxidant, anti-inflammatory, and antimicrobial effects. Previous studies have demonstrated its potential to improve postmenopausal OP, although the exact mechanism remains unclear. This study aims to investigate the anti-osteoporotic mechanism of quercetin based on the "intestinal flora - short-chain fatty acids (SCFAs) - inflammatory" signaling axis.<br><br>METHODS: In this study, we established an ovariectomized (OVX)-induced rat model, quercetin intervention and evaluated the effects on rats following antibiotic (ABX) treatment and fecal microbiota transplantation (FMT). After 6&#xa0;weeks of intervention, the rats were euthanized, and samples from their femur, tibia, lumbar spine, serum, colon and feces were collected, and bone strength, intestinal flora structure, SCFAs levels and cytokine levels were assessed.<br><br>RESULTS: Quercetin modulates the intestinal flora by increasing potentially probiotic bacteria (i.e., Lactobacillales, Prevotellaceae, and Blautia) and decreasing potentially pathogenic bacteria (Desulfobacterota, Erysipelotrichales, Romboutsia, and Butyricoccaceae). It also increases SCFAs content and reduces colonic permeability by enhancing tight junction proteins (ZO-1, Occludin). Furthermore, quercetin lowers proinflammatory cytokine levels (LPS, IL-1&#x3b2;, and TNF-&#x3b1;), which enhances bone strength and prevents OVX-induced bone loss.<br><br>CONCLUSIONS: Quercetin may effectively reduce bone loss in OVX rats via the "intestinal flora - SCFAs - inflammatory" signaling pathway.}, }
@article {pmid38807723, year = {2024}, author = {Kardan, R and Hemmati, J and Nazari, M and Ahmadi, A and Asghari, B and Azizi, M and Khaledi, M and Arabestani, MR}, title = {Novel therapeutic strategy for obesity through the gut microbiota-brain axis: A review article.}, journal = {Caspian journal of internal medicine}, volume = {15}, number = {2}, pages = {215-227}, pmid = {38807723}, issn = {2008-6164}, abstract = {Background: The interaction between commensal bacteria and the host is essential for health and the gut microbiota-brain axis plays a vital role in this regard. Obesity as a medical problem not only affect the health of the individuals, but also the economic and social aspects of communities. The presence of any dysbiosis in the composition of the gut microbiota disrupts in the gut microbiota-brain axis, which in turn leads to an increase in appetite and then obesity. Because common treatments for obesity have several drawbacks, the use of microbiota-based therapy in addition to treatment and prevention of obesity can have other numerous benefits for the individual. In this review, we intend to investigate the relationship between obesity and the gut microbiota-brain axis as well as novel treatment strategies based on this axis with an emphasis on gut microbiota.}, }
@article {pmid38807706, year = {2024}, author = {Gao, T and Li, Y and Wang, X and Ren, F}, title = {Alginate oligosaccharide-mediated butyrate-HIF-1α axis improves skin aging in mice.}, journal = {Journal of pharmaceutical analysis}, volume = {14}, number = {5}, pages = {100911}, pmid = {38807706}, issn = {2214-0883}, abstract = {The "gut-skin" axis has been proved and is considered as a novel therapy for the prevention of skin aging. The antioxidant efficacy of oligomannonic acid (MAOS) make it an intriguing target for use to improve skin aging. The present study further explored whereby MAOS-mediated gut-skin axis balance prevented skin aging in mice. The data indicated the skin aging phenotypes, oxidative stress, skin mitochondrial dysfunction, and intestinal dysbiosis (especially the butyrate and HIF-1α levels decreased) in aging mice. Similarly, fecal microbiota transplantation (FMT) from aging mice rebuild the aging-like phenotypes. Further, we demonstrated MAOS-mediated colonic butyrate-HIF-1α axis homeostasis promoted the entry of butyrate into the skin, upregulated mitophagy level and ultimately improving skin aging via HDAC3/PHD/HIF-1α/mitophagy loop in skin of mice. Overall, our study offered a better insights of the effectiveness of alginate oligosaccharides (AOS), promised to become a personalized targeted therapeutic agents, on gut-skin axis disorder inducing skin aging.}, }
@article {pmid38806933, year = {2024}, author = {Hubert, M}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {166}, number = {10}, pages = {70}, doi = {10.1007/s15006-024-3992-2}, pmid = {38806933}, issn = {1613-3560}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/microbiology ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, }
@article {pmid38804766, year = {2024}, author = {Smith, A and Roy, T}, title = {Fecal Microbiota Spores, Live-Brpk (Vowst) to Prevent Clostridioides difficile Infection.}, journal = {American family physician}, volume = {109}, number = {5}, pages = {472-473}, pmid = {38804766}, issn = {1532-0650}, mesh = {Humans ; *Clostridium Infections/prevention &amp; control ; *Clostridioides difficile ; *Feces/microbiology ; Fecal Microbiota Transplantation/methods ; }, }
@article {pmid38802927, year = {2024}, author = {Zhao, L and Zhang, Z and Wang, P and Zhang, N and Shen, H and Wu, H and Wei, Z and Yang, F and Wang, Y and Yu, Z and Li, H and Hu, Z and Zhai, H and Wang, Z and Su, F and Xie, K and Li, Y}, title = {NHH promotes Sepsis-associated Encephalopathy with the expression of AQP4 in astrocytes through the gut-brain Axis.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {138}, pmid = {38802927}, issn = {1742-2094}, support = {2022MS08002//Natural Science Foundation of Inner Mongolia Autonomous Region/ ; TJWJ2023QN007//Tianjin Municipal Health Commission/ ; 82302413//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Aquaporin 4/metabolism/genetics/biosynthesis ; *Astrocytes/metabolism ; *Hyperammonemia/metabolism ; *Sepsis-Associated Encephalopathy/metabolism ; Male ; *Brain-Gut Axis/physiology ; Mice, Inbred C57BL ; Ammonia/metabolism/blood ; Brain/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.}, }
@article {pmid38800353, year = {2024}, author = {DuPont, HL and DuPont, AW and Tillotson, GS}, title = {Microbiota restoration therapies for recurrent Clostridioides difficile infection reach an important new milestone.}, journal = {Therapeutic advances in gastroenterology}, volume = {17}, number = {}, pages = {17562848241253089}, pmid = {38800353}, issn = {1756-283X}, abstract = {Microbiota restoration therapy has become a standard treatment for recurrent Clostridioides difficile infection (rCDI). In this article, we review the studies supporting the licensure of two live biotherapeutic products (LBPs) designed to prevent rCDI and to provide clinicians with a perspective on their differences. PubMed was reviewed on 1 October 2023, for all papers published concerning the current Food and Drug Administration allowance of the use of fecal microbiota transplantation (FMT) and the studies that led to the licensure of RBX2660 (REBYOTA™), generic name, fecal microbiota, live-jslm, and SER-109 (VOWST™), generic name, fecal microbiota spores, live-brpk. OpenBiome continues to produce fecal products for patients with rCDI at their treatment sites, and the American Gastroenterology Association has a National Registry focused on long-term safety of administering fecal microbiota products. The science behind the licensing of fecal microbiota, live-jslm, a consortium of fecal anaerobes found in stool augmented with strains of Bacteroidetes and fecal microbiota spores, live-brpk, a mixture of 50 species of purified Firmicutes spores is reviewed. Both products appear to be safe in clinical trials and effective in reducing rCDI episodes by mechanisms established for FMT, including normalization of α- and β-diversity of the microbiome and by increasing fecal secondary bile acids. The different makeup of the two LBPs suggests that rCDI responds to a variety of engrafting microbiota which explains why nearly all donors in FMT of rCDI are generally effective. Fecal microbiota, live-jslm has also been shown to successfully treat rCDI in elderly patients with advanced comorbidities. With the licensure of two novel LBPs, we are entering a new phase of microbiota replacement therapy. Having standardized manufacturing and proper monitoring of products, harnessing the microbiome to control and prevent disease has a new beginning.}, }
@article {pmid38799623, year = {2024}, author = {Meng, Q and Guo, J and Lv, K and Liu, Y and Zhang, J and Li, M and Cheng, X and Chen, S and Huo, X and Zhang, Q and Chen, Y and Li, J}, title = {5S-Heudelotinone alleviates experimental colitis by shaping the immune system and enhancing the intestinal barrier in a gut microbiota-dependent manner.}, journal = {Acta pharmaceutica Sinica. B}, volume = {14}, number = {5}, pages = {2153-2176}, pmid = {38799623}, issn = {2211-3835}, abstract = {Aberrant changes in the gut microbiota are implicated in many diseases, including inflammatory bowel disease (IBD). Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity, indicating that microbe-mediated modulation may be a promising strategy for preventing and treating IBD. Although fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies, novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently needed. Herein, we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone (an enantiomer) as a potent agent against experimental colitis that acts by modulating the gut microbiota. 5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids (SCFAs); thus, it regulates the intestinal immune system by reducing proinflammatory immune cell numbers, and maintains intestinal mucosal integrity by modulating tight junctions (TJs). Moreover, 5S-heudelotinone (2) ameliorates colitis-associated colorectal cancer (CAC) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced in situ carcinoma model. Together, these findings reveal the potential of a novel natural product, namely, 5S-heudelotinone, to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.}, }
@article {pmid38797998, year = {2024}, author = {Bourragat, A and Escoula, Q and Bellenger, S and Zemb, O and Beaumont, M and Chaumonnot, K and Farine, JP and Jacotot, E and Bonnotte, A and Avoscan, L and Lherminier, J and Luo, K and Narce, M and Bellenger, J}, title = {The transplantation of the gut microbiome of fat-1 mice protects against colonic mucus layer disruption and endoplasmic reticulum stress induced by high fat diet.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2356270}, pmid = {38797998}, issn = {1949-0984}, mesh = {Animals ; *Endoplasmic Reticulum Stress ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Mice ; Male ; *Fatty Acids, Omega-3/metabolism ; *Colon/microbiology/metabolism ; *Intestinal Mucosa/metabolism/microbiology ; *Mice, Transgenic ; Obesity/metabolism/microbiology ; Mucus/metabolism ; Mice, Inbred C57BL ; Mucins/metabolism ; Goblet Cells/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {High-fat diets alter gut barrier integrity, leading to endotoxemia by impacting epithelial functions and inducing endoplasmic reticulum (ER) stress in intestinal secretory goblet cells. Indeed, ER stress, which is an important contributor to many chronic diseases such as obesity and obesity-related disorders, leads to altered synthesis and secretion of mucins that form the protective mucus barrier. In the present study, we investigated the relative contribution of omega-3 polyunsaturated fatty acid (PUFAs)-modified microbiota to alleviating alterations in intestinal mucus layer thickness and preserving gut barrier integrity. Male fat-1 transgenic mice (exhibiting endogenous omega-3 PUFAs tissue enrichment) and wild-type (WT) littermates were fed either an obesogenic high-fat diet (HFD) or a control diet. Unlike WT mice, HFD-fed fat-1 mice were protected against mucus layer alterations as well as an ER stress-mediated decrease in mucin expression. Moreover, cecal microbiota transferred from fat-1 to WT mice prevented changes in the colonic mucus layer mainly through colonic ER stress downregulation. These findings highlight a novel feature of the preventive effects of omega-3 fatty acids against intestinal permeability in obesity-related conditions.}, }
@article {pmid38797111, year = {2024}, author = {Zhou, L and Fan, S and Zhang, W and Wang, D and Tang, D}, title = {Microbes in the tumor microenvironment: New additions to break the tumor immunotherapy dilemma.}, journal = {Microbiological research}, volume = {285}, number = {}, pages = {127777}, doi = {10.1016/j.micres.2024.127777}, pmid = {38797111}, issn = {1618-0623}, mesh = {*Tumor Microenvironment/immunology ; *Immunotherapy/methods ; Humans ; *Neoplasms/therapy/immunology ; Microbiota/immunology ; Animals ; Probiotics/administration &amp; dosage/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Immunotherapies currently used in clinical practice are unsatisfactory in terms of therapeutic response and toxic side effects, and therefore new immunotherapies need to be explored. Intratumoral microbiota (ITM) exists in the tumor environment (TME) and reacts with its components. On the one hand, ITM promotes antigen delivery to tumor cells or provides cross-antigens to promote immune cells to attack tumors. On the other hand, ITM affects the activity of immune cells and stromal cells. We also summarize the dialog pathways by which ITM crosstalks with components within the TME, particularly the interferon pathway. This interaction between ITM and TME provides new ideas for tumor immunotherapy. By analyzing the bidirectional role of ITM in TME and combining it with its experimental and clinical status, we summarized the adjuvant role of ITM in immunotherapy. We explored the potential applications of using ITM as tumor immunotherapy, such as a healthy diet, fecal transplantation, targeted ITM, antibiotics, and probiotics, to provide a new perspective on the use of ITM in tumor immunotherapy.}, }
@article {pmid38795515, year = {2024}, author = {Liu, M and Li, L and Xue, Y and Sun, M and Xiang, F and Zhao, K and Zhang, W and Lei, B and Shang, C and Hu, Y and Yuan, W}, title = {Effect of intestinal microbiota on duck short-beak and dwarf syndrome caused by novel goose parvovirus.}, journal = {Poultry science}, volume = {103}, number = {7}, pages = {103853}, pmid = {38795515}, issn = {1525-3171}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Ducks ; *Poultry Diseases/virology/microbiology ; *Parvoviridae Infections/veterinary/virology ; *Parvovirinae/genetics/physiology ; Anti-Bacterial Agents/pharmacology/administration &amp; dosage ; Fecal Microbiota Transplantation/veterinary ; }, abstract = {Short-beak and dwarf syndrome (SBDS) is caused by infection with novel goose parvovirus (NGPV), which leads to intestinal dysbiosis, developmental delay, short beak, lameness, and paralysis in ducks and is the cause of skeletal health problems. NGPV infection can cause intestinal microbial disturbances, but it is still unclear whether the intestinal microbiota affects the pathogenicity of NGPV. Here, the effects of intestinal microbiota on NGPV-induced SBDS in Cherry Valley ducks were assessed by establishing a duck model for gut microflora depletion/reestablishment through antibiotics (ABX) treatment/fecal microbiota transplanted (FMT). By measuring body weight, beak length, beak width and tarsal length, we found that SBDS clinical symptoms were alleviated in ducks treated with ABX, but not in FMT ducks. Next, we conducted a comprehensive analysis of bone metabolism, gut barrier integrity, and inflammation levels using quantitative real-time PCR (qPCR), enzyme linked immunosorbent assay (ELISA), biochemical analysis and histological analysis. The results showed that ABX treatment improved bone quality reduced bone resorption, mitigated tissue lesions, protected intestinal barrier integrity, and inhibited systemic inflammation in NGPV-infected ducks. Moreover, cecal microflora composition and short-chain fatty acids (SCFAs) production were examined by bacterial 16S rRNA sequencing and gas chromatography. The results revealed that ABX treatment mitigated the decreased abundance of Firmicutes and Bacteroidota in NGPV-infected ducks, as well as increased SCFAs production. Furthermore, ABX treatment reduced the mucosa-associated lymphoid tissue lymphoma translocation protein 1 (Malt1) and nuclear factor κB (NF-κB) expression, which are correlated with systemic inflammation in SBDS ducks. These findings suggested that intestinal microflora depletion alleviated NGPV-induced SBDS by maintaining intestinal homeostasis, inhibiting inflammatory response and alleviating bone resorption. These results provide evidence for the pivotal role of intestinal microbiota in the process of SBDS and contribute a theoretical basis for the feasibility of microecological preparation as a method to control SBDS.}, }
@article {pmid38794880, year = {2024}, author = {Corte-Iglesias, V and Saiz, ML and Andrade-Lopez, AC and Salazar, N and Bernet, CR and Martin-Martin, C and Borra, JM and Lozano, JJ and Aransay, AM and Diaz-Corte, C and Lopez-Larrea, C and Suarez-Alvarez, B}, title = {Propionate and butyrate counteract renal damage and progression to chronic kidney disease.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {40}, number = {1}, pages = {133-150}, pmid = {38794880}, issn = {1460-2385}, support = {//Instituto de Salud Carlos III/ ; //European Union/ ; IFEQ21/00203//Adquisici&#xf3;n de equipamiento e Infraestructuras cient&#xed;fico-t&#xe9;cnicas/ ; RICORS2040 (RD21/0005/0017)//NextGenerationEU/ ; //Mechanism for Recovery and Resilience (MRR)/RETC/ ; //PCTI-Plan de Ciencia/ ; IDI/2021/000032//Tecnolog&#xed;a e Innovaci&#xf3;n 2021-2023 del Gobierno del Principado de Asturias/FEDER/ ; //Department of Industry, Tourism and Trade of the Government of the Autonomous Community of the Basque Country/ ; //Innovation Technology Department of the Bizkaia County/ ; //MINECO/ ; CEX2021-001136-S//Severo Ochoa Excellence Accreditation/ ; CP18/00106//The Miguel Servet Program from ISCIII/ ; FEDER-PCTI 2021-2023//Gobierno del Principado de Asturias/ ; //Fundaci&#xf3;n para la Investigaci&#xf3;n Biosanitaria of Asturias/ ; }, mesh = {*Renal Insufficiency, Chronic/etiology/drug therapy/metabolism ; Animals ; Humans ; *Butyrates/metabolism ; *Propionates ; Mice ; Male ; *Disease Progression ; Female ; Middle Aged ; Gastrointestinal Microbiome/drug effects ; Glomerular Filtration Rate ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; Feces/microbiology/chemistry ; Disease Models, Animal ; Aged ; Prognosis ; Adult ; Acute Kidney Injury/etiology/prevention &amp; control/metabolism/drug therapy ; }, abstract = {BACKGROUND: Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies.<br><br>METHODS: SCFA levels were measured in chronic kidney disease (CKD) patients (n&#xa0;=&#xa0;54) at different stages of the disease, and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid-induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD.<br><br>RESULTS: Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by tumour necrosis factor-&#x3b1; in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively, prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term.<br><br>CONCLUSIONS: Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.}, }
@article {pmid38793089, year = {2024}, author = {Gyriki, D and Nikolaidis, C and Stavropoulou, E and Bezirtzoglou, I and Tsigalou, C and Vradelis, S and Bezirtzoglou, E}, title = {Exploring the Gut Microbiome's Role in Inflammatory Bowel Disease: Insights and Interventions.}, journal = {Journal of personalized medicine}, volume = {14}, number = {5}, pages = {}, pmid = {38793089}, issn = {2075-4426}, abstract = {Inflammatory Bowel Disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic and relapsing inflammatory condition of the intestine that significantly impairs quality of life and imposes a heavy burden on healthcare systems globally. While the exact etiology of IBD is unclear, it is influenced by genetic, environmental, immunological, and microbial factors. Recent advances highlight the gut microbiome's pivotal role in IBD pathogenesis. The microbial dysbiosis characteristic of IBD, marked by a decline in beneficial bacteria and an increase in pathogenic microbes, suggests a profound connection between microbial imbalance and disease mechanisms. This review explores diagnostic approaches to IBD that integrate clinical assessment with advanced microbiological analyses, highlighting the potential of microbiome profiling as a non-invasive diagnostic tool. In addition, it evaluates conventional and emerging treatments and discusses microbiome-targeted intervention prospects, such as probiotics, symbiotics, and faecal microbiota transplantation. The necessity for future research to establish their efficacy and safety is emphasised.}, }
@article {pmid38792682, year = {2024}, author = {Reveles, KR and Hickmott, AJ and Strey, KA and Mustoe, AC and Arroyo, JP and Power, ML and Ridenhour, BJ and Amato, KR and Ross, CN}, title = {Developing the Common Marmoset as a Translational Geroscience Model to Study the Microbiome and Healthy Aging.}, journal = {Microorganisms}, volume = {12}, number = {5}, pages = {}, pmid = {38792682}, issn = {2076-2607}, support = {UM1 TR004538/TR/NCATS NIH HHS/United States ; U34 AG068482/AG/NIA NIH HHS/United States ; R01AG065546/NH/NIH HHS/United States ; P30 AG013319/AG/NIA NIH HHS/United States ; R01 AG050797/AG/NIA NIH HHS/United States ; R01 AG065546/AG/NIA NIH HHS/United States ; P30 AG044271/AG/NIA NIH HHS/United States ; P51 OD011133/OD/NIH HHS/United States ; }, abstract = {Emerging data support associations between the depletion of the healthy gut microbiome and aging-related physiological decline and disease. In humans, fecal microbiota transplantation (FMT) has been used successfully to restore gut microbiome structure and function and to treat C. difficile infections, but its application to healthy aging has been scarcely investigated. The marmoset is an excellent model for evaluating microbiome-mediated changes with age and interventional treatments due to their relatively shorter lifespan and many social, behavioral, and physiological functions that mimic human aging. Prior work indicates that FMT is safe in marmosets and may successfully mediate gut microbiome function and host health. This narrative review (1) provides an overview of the rationale for FMT to support healthy aging using the marmoset as a translational geroscience model, (2) summarizes the prior use of FMT in marmosets, (3) outlines a protocol synthesized from prior literature for studying FMT in aging marmosets, and (4) describes limitations, knowledge gaps, and future research needs in this field.}, }
@article {pmid38791997, year = {2024}, author = {Machado, AP and Shaikh, AS and Saji, A and Shatila, M and Oliva, IG and Wang, Y and Shirwaikar Thomas, A}, title = {Outcomes of Budesonide as a Treatment Option for Immune Checkpoint Inhibitor-Related Colitis in Patients with Cancer.}, journal = {Cancers}, volume = {16}, number = {10}, pages = {}, pmid = {38791997}, issn = {2072-6694}, abstract = {BACKGROUND: Current treatment guidelines for moderate to severe colitis (IMC) secondary to immune checkpoint inhibitors (ICI) recommend systemic corticosteroids as the primary therapy in conjunction with biologics, namely infliximab and/or vedolizumab. We aimed to explore the efficacy and safety of oral budesonide in the treatment of IMC.<br><br>METHODS: We performed a retrospective analysis at MD Anderson Cancer Center of adult cancer patients with a confirmed (based on clinical, radiographic and laboratory assessment) diagnosis of IMC between 1 January 2015 and 31 November 2022, treated with budesonide. Data collection included demographics, oncologic history, IMC-related information and outcomes up to 6 months after the last dose of ICI.<br><br>RESULTS: Our sample (n = 69) comprised primarily of Caucasian (76.8%) females (55.1%). The majority of patients received combination therapy with anti-PD-1/L1 and anti-CTLA-4 (49.3%), and the most common malignancy treated was melanoma (37.6%). The median grade of diarrhea was 3 and of colitis was 2. Of the 50 patients who underwent endoscopic evaluation, a majority had non-ulcerative inflammation (64%) and active colitis on histology (78%). Budesonide was used as primary treatment at onset of IMC in 56.5% patients, as well as a bridging therapy from systemic corticosteroids in 33.3%. Less than half of the patients (44.9%) required additional therapies such as biologics or fecal microbiota transplant. Additionally, 75.3% of patients achieved full remission of IMC and 24.6% had a recurrence of IMC. ICI was resumed in 31.9% of patients and 17.4% received other forms of cancer therapies.<br><br>CONCLUSIONS: Budesonide may be an effective strategy to treat and prevent the recurrence of IMC. The remission rates observed in our analysis with budesonide alone are comparable to systemic corticosteroids. Patients that require an extended duration of steroid exposure and those with moderate to severe colitis may benefit from budesonide given its lower risk of infection and complications. Furthermore, we observe that budesonide may serve as a successful bridge from systemic corticosteroids with subsequent biologic treatment. Larger prospective studies are necessary to determine the role of budesonide as well as its safety profile.}, }
@article {pmid38791599, year = {2024}, author = {Olteanu, G and Ciucă-Pană, MA and Busnatu, &#x218;S and Lupuliasa, D and Neacșu, SM and Mititelu, M and Musuc, AM and Ioniță-Mîndrican, CB and Boroghină, SC}, title = {Unraveling the Microbiome-Human Body Axis: A Comprehensive Examination of Therapeutic Strategies, Interactions and Implications.}, journal = {International journal of molecular sciences}, volume = {25}, number = {10}, pages = {}, pmid = {38791599}, issn = {1422-0067}, mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Microbiota ; Animals ; Human Body ; Host Microbial Interactions/physiology ; }, abstract = {This review scrutinizes the intricate interplay between the microbiome and the human body, exploring its multifaceted dimensions and far-reaching implications. The human microbiome, comprising diverse microbial communities inhabiting various anatomical niches, is increasingly recognized as a critical determinant of human health and disease. Through an extensive examination of current research, this review elucidates the dynamic interactions between the microbiome and host physiology across multiple organ systems. Key topics include the establishment and maintenance of microbiota diversity, the influence of host factors on microbial composition, and the bidirectional communication pathways between microbiota and host cells. Furthermore, we delve into the functional implications of microbiome dysbiosis in disease states, emphasizing its role in shaping immune responses, metabolic processes, and neurological functions. Additionally, this review discusses emerging therapeutic strategies aimed at modulating the microbiome to restore host-microbe homeostasis and promote health. Microbiota fecal transplantation represents a groundbreaking therapeutic approach in the management of dysbiosis-related diseases, offering a promising avenue for restoring microbial balance within the gut ecosystem. This innovative therapy involves the transfer of fecal microbiota from a healthy donor to an individual suffering from dysbiosis, aiming to replenish beneficial microbial populations and mitigate pathological imbalances. By synthesizing findings from diverse fields, this review offers valuable insights into the complex relationship between the microbiome and the human body, highlighting avenues for future research and clinical interventions.}, }
@article {pmid38789466, year = {2024}, author = {Algavi, YM and Borenstein, E}, title = {Relative dispersion ratios following fecal microbiota transplant elucidate principles governing microbial migration dynamics.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4447}, pmid = {38789466}, issn = {2041-1723}, support = {U19 AG057377/AG/NIA NIH HHS/United States ; 2435/19//Israel Science Foundation (ISF)/ ; U19AG057377//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; }, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome/physiology ; *Feces/microbiology ; Gastrointestinal Tract/microbiology ; Bacteria/metabolism/genetics/classification ; }, abstract = {Microorganisms frequently migrate from one ecosystem to another. Yet, despite the potential importance of this process in modulating the environment and the microbial ecosystem, our understanding of the fundamental forces that govern microbial dispersion is still lacking. Moreover, while theoretical models and in-vitro experiments have highlighted the contribution of species interactions to community assembly, identifying such interactions in vivo, specifically in communities as complex as the human gut, remains challenging. To address this gap, here we introduce a robust and rigorous computational framework, termed Relative Dispersion Ratio (RDR) analysis, and leverage data from well-characterized fecal microbiota transplant trials, to rigorously pinpoint dependencies between taxa during the colonization of human gastrointestinal tract. Our analysis identifies numerous pairwise dependencies between co-colonizing microbes during migration between gastrointestinal environments. We further demonstrate that identified dependencies agree with previously reported findings from in-vitro experiments and population-wide distribution patterns. Finally, we explore metabolic dependencies between these taxa and characterize the functional properties that facilitate effective dispersion. Collectively, our findings provide insights into the principles and determinants of community dynamics following ecological translocation, informing potential opportunities for precise community design.}, }
@article {pmid38788981, year = {2024}, author = {Ketagoda, DHK and Varga, P and Fitzsimmons, TR and Moore, NE and Weyrich, LS and Zilm, PS}, title = {Development of an in vitro biofilm model of the human supra-gingival microbiome for Oral microbiome transplantation.}, journal = {Journal of microbiological methods}, volume = {223}, number = {}, pages = {106961}, doi = {10.1016/j.mimet.2024.106961}, pmid = {38788981}, issn = {1872-8359}, mesh = {*Biofilms/growth &amp; development ; Humans ; *Microbiota ; *Mouth/microbiology ; *Bacteria/genetics/classification/isolation &amp; purification ; Gingiva/microbiology ; Dental Plaque/microbiology ; Saliva/microbiology ; Microscopy, Confocal ; High-Throughput Nucleotide Sequencing ; Fecal Microbiota Transplantation/methods ; Dental Caries/microbiology/therapy ; }, abstract = {The high prevalence of dental caries and periodontal disease place a significant burden on society, both socially and economically. Recent advances in genomic technologies have linked both diseases to shifts in the oral microbiota - a community of >700 bacterial species that live within the mouth. The development of oral microbiome transplantation draws on the success of fecal microbiome transplantation for the treatment of gut pathologies associated with disease. Many current in vitro oral biofilm models have been developed but do not fully capture the complexity of the oral microbiome which is required for successful OMT. To address this, we developed an in vitro biofilm system that maintained an oral microbiome with 252 species on average over 14 days. Six human plaque samples were grown in 3D printed flow cells on hydroxyapatite discs using artificial saliva medium (ASM). Biofilm composition and growth were monitored by high throughput sequencing and confocal microscopy/SEM, respectively. While a significant drop in bacterial diversity occurred, up to 291 species were maintained in some flow cells over 14 days with 70% viability grown with ASM. This novel in vitro biofilm model represents a marked improvement on existing oral biofilm systems and provides new opportunities to develop oral microbiome transplant therapies.}, }
@article {pmid38788915, year = {2025}, author = {Caenepeel, C and Deleu, S and Vazquez Castellanos, JF and Arnauts, K and Braekeleire, S and Machiels, K and Baert, F and Mana, F and Pouillon, L and Hindryckx, P and Lobaton, T and Louis, E and Franchimont, D and Verstockt, B and Ferrante, M and Sabino, J and Vieira-Silva, S and Falony, G and Raes, J and Vermeire, S}, title = {Rigorous Donor Selection for Fecal Microbiota Transplantation in Active Ulcerative Colitis: Key Lessons From a Randomized Controlled Trial Halted for Futility.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {23}, number = {4}, pages = {621-631.e7}, doi = {10.1016/j.cgh.2024.05.017}, pmid = {38788915}, issn = {1542-7714}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy ; Male ; Female ; Middle Aged ; Adult ; Double-Blind Method ; *Donor Selection/methods ; Treatment Outcome ; Medical Futility ; Remission Induction ; Aged ; Gastrointestinal Microbiome ; }, abstract = {BACKGROUND &amp; AIMS: Rigorous donor preselection on microbiota level, strict anaerobic processing, and repeated fecal microbiota transplantation (FMT) administration were hypothesized to improve FMT induction of remission in ulcerative colitis (UC).<br><br>METHODS: The RESTORE-UC trial was a multi-centric, double-blind, sham-controlled, randomized trial. Patients with moderate to severe UC (defined by total Mayo 4-10) were randomly allocated to receive 4 anaerobic-prepared allogenic or autologous donor FMTs. Allogenic donor material was selected after a rigorous screening based on microbial cell count, enterotype, and the abundance of specific genera. The primary endpoint was steroid-free clinical remission (total Mayo &#x2264;2, no sub-score >1) at week 8. A pre-planned futility analysis was performed after 66% (n&#xa0;= 72) of intended inclusions (n&#xa0;= 108). Quantitative microbiome profiling (n&#xa0;= 44) was performed at weeks 0 and&#xa0;8.<br><br>RESULTS: In total, 72 patients were included, of which 66 received at least 1 FMT (allogenic FMT, n&#xa0;= 30 and autologous FMT, n&#xa0;= 36). At week 8, respectively, 3 and 5 patients reached the primary endpoint of steroid-free clinical remission (P&#xa0;= .72), indicating no treatment difference of at least 5% in favor of allogenic FMT. Hence, the study was stopped due to futility. Microbiome analysis showed numerically more enterotype transitions upon allogenic FMT compared with autologous FMT, and more transitions were observed when patients were treated with a different enterotype than their own at baseline (P&#xa0;= .01). Primary response was associated with lower total Mayo scores, lower bacterial cell counts, and higher Bacteroides 2 prevalence at baseline.<br><br>CONCLUSION: The RESTORE-UC trial did not meet its primary endpoint of increased steroid-free clinical remission at week 8. Further research should additionally consider patient selection, sterilized sham-control, increased frequency, density, and viability of FMT prior to administration.<br><br>CLINICALTRIALS: gov, Number: NCT03110289.}, }
@article {pmid38788173, year = {2024}, author = {Nguyen, CB and Vaishampayan, UN}, title = {Clinical Applications of the Gut Microbiome in Genitourinary Cancers.}, journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting}, volume = {44}, number = {3}, pages = {e100041}, doi = {10.1200/EDBK_100041}, pmid = {38788173}, issn = {1548-8756}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Urogenital Neoplasms/microbiology ; Immunotherapy/methods ; Probiotics/therapeutic use ; }, abstract = {Recently recognized as one of the hallmarks of cancer, the microbiome consists of symbiotic microorganisms that play pivotal roles in carcinogenesis, the tumor microenvironment, and responses to therapy. With recent advances in microbiome metagenomic sequencing, a growing body of work has demonstrated that changes in gut microbiome composition are associated with differential responses to immune checkpoint inhibitors (ICIs) because of alterations in cytokine signaling and cytotoxic T-cell recruitment. Therefore, strategies to shape the gut microbiome into a more favorable, immunogenic profile may lead to improved responses with ICIs. Immunotherapy is commonly used in genitourinary (GU) cancers such as renal cell carcinoma, urothelial cancer, and to a limited extent, prostate cancer. However, a subset of patients do not derive clinical benefit with ICIs. Gut microbiome-based interventions are of particular interest given the potential to boost responses to ICIs in preclinical and early-phase prospective studies. Novel approaches using probiotic therapy (live bacterial supplementation) and fecal microbiota transplantation in patients with GU cancers are currently under investigation.}, }
@article {pmid38786164, year = {2024}, author = {Wang, Y and Hunt, A and Danziger, L and Drwiega, EN}, title = {A Comparison of Currently Available and Investigational Fecal Microbiota Transplant Products for Recurrent Clostridioides difficile Infection.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {5}, pages = {}, pmid = {38786164}, issn = {2079-6382}, abstract = {Clostridioides difficile infection (CDI) is an intestinal infection that causes morbidity and mortality and places significant burden and cost on the healthcare system, especially in recurrent cases. Antibiotic overuse is well recognized as the leading cause of CDI in high-risk patients, and studies have demonstrated that even short-term antibiotic exposure can cause a large and persistent disturbance to human colonic microbiota. The recovery and sustainability of the gut microbiome after dysbiosis have been associated with fewer CDI recurrences. Fecal microbiota transplantation (FMT) refers to the procedure in which human donor stool is processed and transplanted to a patient with CDI. It has been historically used in patients with pseudomembranous colitis even before the discovery of Clostridioides difficile. More recent research supports the use of FMT as part of the standard therapy of recurrent CDI. This article will be an in-depth review of five microbiome therapeutic products that are either under investigation or currently commercially available: Rebyota (fecal microbiota, live-jslm, formerly RBX2660), Vowst (fecal microbiota spores, live-brpk, formerly SER109), VE303, CP101, and RBX7455. Included in this review is a comparison of the products' composition and dosage forms, available safety and efficacy data, and investigational status.}, }
@article {pmid38786141, year = {2024}, author = {Abbas, W and Bi, R and Hussain, MD and Tajdar, A and Guo, F and Guo, Y and Wang, Z}, title = {Antibiotic Cocktail Effects on Intestinal Microbial Community, Barrier Function, and Immune Function in Early Broiler Chickens.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {5}, pages = {}, pmid = {38786141}, issn = {2079-6382}, support = {No. 32172774//National Natural Science Foundation of China/ ; (No. 32172774)//National Natural Science Foundation of China/ ; }, abstract = {This study investigated the effects of an antibiotic cocktail on intestinal microbial composition, mechanical barrier structure, and immune functions in early broilers. One-day-old healthy male broiler chicks were treated with a broad-spectrum antibiotic cocktail (ABX; neomycin, ampicillin, metronidazole, vancomycin, and kanamycin, 0.5 g/L each) or not in drinking water for 7 and 14 days, respectively. Sequencing of 16S rRNA revealed that ABX treatment significantly reduced relative Firmicutes, unclassified Lachnospiraceae, unclassified Oscillospiraceae, Ruminococcus torques, and unclassified Ruminococcaceae abundance in the cecum and relative Firmicutes, Lactobacillus and Baccillus abundance in the ileum, but significantly increased richness (Chao and ACE indices) and relative Enterococcus abundance in the ileum and cecum along with relatively enriched Bacteroidetes, Proteobacteria, Cyanobacteria, and Enterococcus levels in the ileum following ABX treatment for 14 days. ABX treatment for 14 days also significantly decreased intestinal weight and length, along with villus height (VH) and crypt depth (CD) of the small intestine, and remarkably increased serum LPS, TNF-α, IFN-γ, and IgG levels, as well as intestinal mucosa DAO and MPO activity. Moreover, prolonged use of ABX significantly downregulated occludin, ZO-1, and mucin 2 gene expression, along with goblet cell numbers in the ileum. Additionally, chickens given ABX for 14 days had lower acetic acid, butyric acid, and isobutyric acid content in the cecum than the chickens treated with ABX for 7 days and untreated chickens. Spearman correlation analysis found that those decreased potential beneficial bacteria were positively correlated with gut health-related indices, while those increased potential pathogenic strains were positively correlated with gut inflammation and gut injury-related parameters. Taken together, prolonged ABX application increased antibiotic-resistant species abundance, induced gut microbiota dysbiosis, delayed intestinal morphological development, disrupted intestinal barrier function, and perturbed immune response in early chickens. This study provides a reliable lower-bacteria chicken model for further investigation of the function of certain beneficial bacteria in the gut by fecal microbiota transplantation into germ-free or antibiotic-treated chickens.}, }
@article {pmid38785512, year = {2024}, author = {Panaitescu, P&#x218; and Răzniceanu, V and Mocrei-Rebrean, &#x218;M and Neculicioiu, VS and Dragoș, HM and Costache, C and Filip, GA}, title = {The Effect of Gut Microbiota-Targeted Interventions on Neuroinflammation and Motor Function in Parkinson's Disease Animal Models-A Systematic Review.}, journal = {Current issues in molecular biology}, volume = {46}, number = {5}, pages = {3946-3974}, pmid = {38785512}, issn = {1467-3045}, abstract = {Gut microbiome-targeted interventions such as fecal transplant, prebiotics, probiotics, synbiotics, and antibiotic gut depletion are speculated to be of potential use in delaying the onset and progression of Parkinson's disease by rebalancing the gut microbiome in the context of the gut-brain axis. Our study aims to organize recent findings regarding these interventions in Parkinson's disease animal models to identify how they affect neuroinflammation and motor outcomes. A systematic literature search was applied in PubMed, Web of Science, Embase, and SCOPUS for gut microbiome-targeted non-dietary interventions. Studies that investigated gut-targeted interventions by using in vivo murine PD models to follow dopaminergic cell loss, motor tests, and neuroinflammatory markers as outcomes were considered to be eligible. A total of 1335 studies were identified in the databases, out of which 29 were found to be eligible. A narrative systematization of the resulting data was performed, and the effect direction for the outcomes was represented. Quality assessment using the SYRCLE risk of bias tool was also performed. Out of the 29 eligible studies, we found that a significant majority report that the intervention reduced the dopaminergic cell loss (82.76%, 95% CI [64.23%, 94.15%]) produced by the induction of the disease model. Also, most studies reported a reduction in microglial (87.5%, 95% CI [61.65%, 98.45%]) and astrocytic activation (84,62%, 95% CI [54.55%, 98.08%]) caused by the induction of the disease model. These results were also mirrored in the majority (96.4% 95% CI [81.65%, 99.91%]) of the studies reporting an increase in performance in behavioral motor tests. A significant limitation of the study was that insufficient information was found in the studies to assess specific causes of the risk of bias. These results show that non-dietary gut microbiome-targeted interventions can improve neuroinflammatory and motor outcomes in acute Parkinson's disease animal models. Further studies are needed to clarify if these benefits transfer to the long-term pathogenesis of the disease, which is not yet fully understood. The study had no funding source, and the protocol was registered in the PROSPERO database with the ID number CRD42023461495.}, }
@article {pmid38784794, year = {2024}, author = {Obaid, NA}, title = {Alternative treatment of recurrent Clostridioides difficile infection in adults by fecal transplantation: an overview of phase I-IV studies from Clinicaltrials.gov.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1374774}, pmid = {38784794}, issn = {1664-302X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an interventional approach to treat chronic and recurrent Clostridioides difficile infection (CDI). However, there is insufficient evidence regarding its effectiveness and safety. Clinical trials have been conducted to inspect the safety and effectiveness of FMT with and without comparison to pharmacological treatments.<br><br>AIM: This review explored the treatment of CDI in adults using FMT and evaluated the safety of this intervention based on phase I-IV studies registered on Clinicaltrials.gov.<br><br>METHOD: A comprehensive search of Clinicaltrials.gov was conducted to identify relevant studies that investigated CDI in adults. Data on study type, study design, sample size, intervention details, and outcomes related to FMT were examined and evaluated.<br><br>RESULTS: In total, 13 clinical trials on FMT for CDI published through 17 November 2023 were identified, all of which were interventional studies. The investigation focused on both terminated and completed studies. Basic and advanced outcome measures were examined.<br><br>CONCLUSION: Some studies were terminated during phase II, and FMT was less effective than antibiotics such as vancomycin and fidaxomicin. However, colonoscopy and oral FMT were explored in several completed studies with promising results, but the evidence remains limited and inconclusive.}, }
@article {pmid38783921, year = {2024}, author = {Li, Y and Xiao, P and Cao, R and Le, J and Xu, Q and Xiao, F and Ye, L and Wang, X and Wang, Y and Zhang, T}, title = {Effects and microbiota changes following oral lyophilized fecal microbiota transplantation in children with autism spectrum disorder.}, journal = {Frontiers in pediatrics}, volume = {12}, number = {}, pages = {1369823}, pmid = {38783921}, issn = {2296-2360}, abstract = {BACKGROUND AND PURPOSE: Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental disorders that is characterized by core features in social communication impairment and restricted, repetitive sensory-motor behaviors. This study aimed to further investigate the utilization of fecal microbiota transplantation (FMT) in children with ASD, both with and without gastrointestinal (GI) symptoms, evaluate the effect of FMT and analyze the alterations in bacterial and fungal composition within the gut microbiota.<br><br>METHODS: A total of 38 children diagnosed with ASD participated in the study and underwent oral lyophilized FMT treatment. The dosage of the FMT treatment was determined based on a ratio of 1&#x2005;g of donor stool per 1&#x2005;kg of recipient body weight, with a frequency of once every 4 weeks for a total of 12 weeks. In addition, 30 healthy controls (HC) were included in the analysis. The clinical efficacy of FMT was evaluated, while the composition of fecal bacteria and fungi was determined using 16S rRNA and ITS gene sequencing methods.<br><br>RESULTS: Median age of the 38 children with ASD was 7 years. Among these children, 84.2% (32 of 38) were boys and 81.6% (31 of 38) exhibited GI symptoms, with indigestion, constipation and diarrhea being the most common symptoms. Sample collections and assessments were conducted at baseline (week 0), post-treatment (week 12) and follow-up (week 20). At the end of the follow-up phase after FMT treatment, the autism behavior checklist (ABC) scores decreased by 23% from baseline, and there was a 10% reduction in scores on the childhood autism rating scale (CARS), a 6% reduction in scores on the social responsiveness scale (SRS) and a 10% reduction in scores on the sleep disturbance scale for children (SDSC). In addition, short-term adverse events observed included vomiting and fever in 2 participants, which were self-limiting and resolved within 24&#x2005;h, and no long-term adverse events were observed. Although there was no significant difference in alpha and beta diversity in children with ASD before and after FMT therapy, the FMT treatment resulted in alterations in the relative abundances of various bacterial and fungal genera in the samples of ASD patients. Comparisons between children with ASD and healthy controls (HC) revealed statistically significant differences in microbial abundance before and after FMT. Blautia, Sellimonas, Saccharomycopsis and Cystobasidium were more abundant in children with ASD than in HC, while Dorea were less abundant. After FMT treatment, levels of Blautia, Sellimonas, Saccharomycopsis and Cystobasidium decreased, while levels of Dorea increased. Moreover, the increased abundances of Fusicatenibacter, Erysipelotrichaceae_UCG-003, Saccharomyces, Rhodotorula, Cutaneotrichosporon and Zygosaccharomyces were negatively correlated with the scores of ASD core symptoms.<br><br>CONCLUSIONS: Oral lyophilized FMT could improve GI and ASD related symptoms, as well as sleep disturbances, and alter the gut bacterial and fungal microbiota composition in children with ASD.<br><br>CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055943. Registered 28 January 2022, www.chictr.org.cn.}, }
@article {pmid38783798, year = {2024}, author = {Ma, X and Zhang, L and Gao, J and Chen, F}, title = {[Advances in the application of fecal microbiota transplantation for the treatment of nervous system diseases].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {40}, number = {5}, pages = {1293-1308}, doi = {10.13345/j.cjb.230448}, pmid = {38783798}, issn = {1872-2075}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; Animals ; *Nervous System Diseases/therapy/microbiology ; Brain-Gut Axis ; Parkinson Disease/therapy/microbiology ; Alzheimer Disease/therapy/microbiology ; Depression/therapy/microbiology ; }, abstract = {The intestinal microbiota exhibits a strong correlation with the function of the central nervous system, exerting influence on the host brain through neural pathways, immune pathways, and microbial metabolites along the gut-brain axis. Disorders in the composition of the intestinal microbial are closely associated with the onset and progression of neurological disorders, such as depression, Alzheimer's disease, and Parkinson's disease. It has been proven that fecal microbiota transplantation can improve symptoms in animal models of neurological diseases and clinical patients. This paper provides a comprehensive review of the composition and function of the human intestinal microbiota, as well as the intricate the relationship between the human intestinal microbiota and nervous system diseases through the gut-brain axis. Additionally, it delves into the research advancements and underlying mechanism of fecal microbiota transplantation in the treatment of nervous system diseases. These findings offer novel insights and potential avenues for clinical interventions targeting nervous system diseases.}, }
@article {pmid38783543, year = {2024}, author = {Horváthová, T and Lafuente, E and Bartels, JA and Wallisch, J and Vorburger, C}, title = {Tolerance to environmental pollution in the freshwater crustacean Asellus aquaticus: A role for the microbiome.}, journal = {Environmental microbiology reports}, volume = {16}, number = {3}, pages = {e13252}, pmid = {38783543}, issn = {1758-2229}, support = {//DUE-Mobil Grant from the University of Duisburg-Essen/ ; CZ.02.2.69/0.0/0.0/20_079/0017809//Ministry of Education, Youth and Sports of the Czech Republic/ ; 5221.00979.008.08//Eawag Academic Transition Grant/ ; //Individual Travel Grant from the Radboud University Nijmegen/ ; }, mesh = {Animals ; *Fresh Water/microbiology/chemistry ; *Microbiota/drug effects ; *Isopoda/microbiology ; Feces/microbiology ; Water Pollutants, Chemical ; Bacteria/classification/isolation &amp; purification/genetics/drug effects ; Environmental Pollution ; }, abstract = {Freshwater habitats are frequently contaminated by diverse chemicals of anthropogenic origin, collectively referred to as micropollutants, that can have detrimental effects on aquatic life. The animals' tolerance to micropollutants may be mediated by their microbiome. If polluted aquatic environments select for contaminant-degrading microbes, the acquisition of such microbes by the host may increase its tolerance to pollution. Here we tested for the potential effects of the host microbiome on the growth and survival of juvenile Asellus aquaticus, a widespread freshwater crustacean. Using faecal microbiome transplants, we provided newly hatched juveniles with the microbiome isolated from donor adults reared in either clean or micropollutant-contaminated water and, after transplantation, recipient juveniles were reared in water with and without micropollutants. The experiment revealed a significant negative effect of the micropollutants on the survival of juvenile isopods regardless of the received faecal microbiome. The micropollutants had altered the composition of the bacterial component of the donors' microbiome, which in turn influenced the microbiome of juvenile recipients. Hence, we show that relatively high environmental concentrations of micropollutants reduce survival and alter the microbiome composition of juvenile A. aquaticus, but we have no evidence that tolerance to micropollutants is modulated by their microbiome.}, }
@article {pmid38782893, year = {2024}, author = {Chen, H and Fu, X and Wu, X and Zhao, J and Qiu, F and Wang, Z and Wang, Z and Chen, X and Xie, D and Huang, J and Fan, J and Yang, X and Song, Y and Li, J and He, D and Xiao, G and Lu, A and Liang, C}, title = {Gut microbial metabolite targets HDAC3-FOXK1-interferon axis in fibroblast-like synoviocytes to ameliorate rheumatoid arthritis.}, journal = {Bone research}, volume = {12}, number = {1}, pages = {31}, pmid = {38782893}, issn = {2095-4700}, support = {82172386//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81922081//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82100943//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2021KTSCX104//Department of Education of Guangdong Province (Guangdong Province Education Department)/ ; }, mesh = {Animals ; Humans ; Male ; Mice ; *Arthritis, Experimental/pathology/metabolism ; *Arthritis, Rheumatoid/metabolism/pathology/drug therapy/microbiology ; Fibroblasts/metabolism/drug effects ; Forkhead Transcription Factors/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Histone Deacetylases/metabolism ; *Mice, Inbred C57BL ; Mice, Inbred DBA ; Signal Transduction/drug effects ; *Synoviocytes/metabolism/drug effects/pathology ; }, abstract = {Rheumatoid arthritis (RA) is an autoimmune disease. Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility. However, accumulating evidence demonstrates that genetics also shape the gut microbiota. It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis (CIA), while the others are resistant to CIA. Here, we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice. C57BL/6J mice and healthy human individuals have enriched B. fragilis than DBA/1J mice and RA patients. Transplantation of B. fragilis prevents CIA in DBA/1J mice. We identify that B. fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate. Fibroblast-like synoviocytes (FLSs) in RA are activated to undergo tumor-like transformation. Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1, resulting in reduced FOXK1 stability, blocked interferon signaling and deactivation of RA-FLSs. We treat CIA mice with propionate and show that propionate attenuates CIA. Moreover, a combination of propionate with anti-TNF etanercept synergistically relieves CIA. These results suggest that B. fragilis or propionate could be an alternative or complementary approach to the current therapies.}, }
@article {pmid38782148, year = {2024}, author = {Wu, C and Wu, C and Peng, L and Wu, M and Li, Z and Chen, J}, title = {Multi-omics approaches for the understanding of therapeutic mechanism for Huang-Qi-Long-Dan Granule against ischemic stroke.}, journal = {Pharmacological research}, volume = {205}, number = {}, pages = {107229}, doi = {10.1016/j.phrs.2024.107229}, pmid = {38782148}, issn = {1096-1186}, mesh = {Animals ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Male ; *Ischemic Stroke/metabolism/drug therapy ; *Mice, Inbred C57BL ; Mice ; *Metabolomics ; Tryptophan/metabolism ; Astragalus propinquus ; Neuroprotective Agents/pharmacology/therapeutic use ; Brain/metabolism/drug effects ; Cytokines/metabolism ; Th17 Cells/drug effects/metabolism ; Infarction, Middle Cerebral Artery/drug therapy/metabolism ; Disease Models, Animal ; Multiomics ; Receptors, Aryl Hydrocarbon ; Basic Helix-Loop-Helix Transcription Factors ; }, abstract = {After long-term clinical application, traditional Chinese medicine (TCM) has accumulated rich experience in the stroke treatment. Huang-Qi-Long-Dan Granule (HQLDG) is a TCM formula that has been used in clinical for the treatment of acute ischemic stroke. However, its mechanism against ischemic stroke is still unknown. This study aimed to identify HQLDG's effect against ischemic stroke and explore its underlying mechanism. 16s rRNA sequencing, metabolomics/tryptophan (Trp)-targeted metabolomics analysis and transcriptomic analysis were used to investigate HQLDG underlying therapeutic mechanism. Our results revealed that HQLDG significantly decreased the infarct volume, improved mouse behavior and brain slices pathological staining. In addition, it could ameliorate intestinal barrier damage and regulate tight junction gene expression. 16s rRNA, metabolomics and transcriptomics analysis revealed that HQLDG treatment significantly improved the composition of gut microbiota and Trp metabolism pathway, and further downregulated Th17/IL-17 signaling pathway. HQLDG treatment could significantly decrease serum inflammatory cytokines, IL-17A and IL-22; down-regulate Trp metabolism receptor gene (Ahr), inflammatory cytokines genes (IL-17a, IL-22), and an important coding gene for maintaining the mature Th17 (rorc) in both brain and intestinal tissues. In the contrary, after gut microbiota removal, this effect of HQLDG was impaired. HQLDG treated mouse fecal microbiota transplantation also had positive effect against tMCAO injury. Moreover, AhR inhibitor could decrease IL-17A immunofluorescence. These results suggested that the gut microbiota regulation might be an important intermediate in HQLDG against tMCAO injury. HQLDG might exert anti-ischemic stroke effects through the gut microbiota-Trp metabolism-Th17/IL-17 signaling, which provides new insights into HQLDG-mediated prevention in ischemic stroke.}, }
@article {pmid38781732, year = {2024}, author = {Wu, G and Liao, J and Zhu, X and Zhang, Y and Lin, Y and Zeng, Y and Zhao, J and Zhang, J and Yao, T and Shen, X and Li, H and Hu, L and Zhang, W}, title = {Shexiang Baoxin Pill enriches Lactobacillus to regulate purine metabolism in patients with stable coronary artery disease.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {130}, number = {}, pages = {155727}, doi = {10.1016/j.phymed.2024.155727}, pmid = {38781732}, issn = {1618-095X}, mesh = {Animals ; *Coronary Artery Disease/drug therapy ; *Purines ; Male ; Humans ; *Drugs, Chinese Herbal/pharmacology ; *Inosine/pharmacology ; *Myocardial Infarction ; Middle Aged ; Rats ; *Lactobacillus/drug effects ; Female ; Disease Models, Animal ; Rats, Sprague-Dawley ; Aged ; Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: It has been clinically confirmed that the Shexiang Baoxin Pill (SBP) dramatically reduces the frequency of angina in patients with stable coronary artery disease (SCAD). However, potential therapeutic mechanism of SBP has not been fully explored.<br><br>PURPOSE: The study explored the therapeutic mechanism of SBP in the treatment of SCAD patients.<br><br>METHODS: We examined the serum metabolic profiles of patients with SCAD following SBP treatment. A rat model of acute myocardial infarction (AMI) was established, and the potential therapeutic mechanism of SBP was explored using metabolomics, transcriptomics, and 16S rRNA sequencing.<br><br>RESULTS: SBP decreased inosine production and improved purine metabolic disorders in patients with SCAD and in animal models of AMI. Inosine was implicated as a potential biomarker for SBP efficacy. Furthermore, SBP inhibited the expression of genes involved in purine metabolism, which are closely associated with thrombosis, inflammation, and platelet function. The regulation of purine metabolism by SBP was associated with the enrichment of Lactobacillus. Finally, the effects of SBP on inosine production and vascular function could be transmitted through the transplantation of fecal microbiota.<br><br>CONCLUSION: Our study reveals a novel mechanism by which SBP regulates purine metabolism by enriching Lactobacillus to exert cardioprotective effects in patients with SCAD. The data also provide previously undocumented evidence indicating that inosine is a potential biomarker for evaluating the efficacy of SBP in the treatment of SCAD.}, }
@article {pmid38780275, year = {2024}, author = {Cai, L and Wang, X and Zhu, X and Xu, Y and Qin, W and Ren, J and Jiang, Q and Yan, X}, title = {Lactobacillus-derived protoporphyrin IX and SCFAs regulate the fiber size via glucose metabolism in the skeletal muscle of chickens.}, journal = {mSystems}, volume = {9}, number = {6}, pages = {e0021424}, pmid = {38780275}, issn = {2379-5077}, support = {2023YFD1301304//the National Key Research and Development Project/ ; Project 2662023DKPY002//MOE | Fundamental Research Funds for the Central Universities (Fundamental Research Fund for the Central Universities)/ ; 2019TQ0108//China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)/ ; }, mesh = {Animals ; *Chickens/metabolism/microbiology ; *Glucose/metabolism ; *Gastrointestinal Microbiome/physiology ; *Fatty Acids, Volatile/metabolism ; *Lactobacillus/metabolism ; Muscle, Skeletal/metabolism ; Muscle Fibers, Skeletal/metabolism ; Energy Metabolism ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiota contributes to skeletal muscle energy metabolism and is an indirect factor affecting meat quality. However, the role of specific gut microbes in energy metabolism and fiber size of skeletal muscle in chickens remains largely unknown. In this study, we first performed cecal microbiota transplantation from Chinese indigenous Jingyuan chickens (JY) to Arbor Acres chickens (AA), to determine the effects of microbiota on skeletal muscle fiber and energy metabolism. Then, we used metagenomics, gas chromatography, and metabolomics analysis to identify functional microbes. Finally, we validated the role of these functional microbes in regulating the fiber size via glucose metabolism in the skeletal muscle of chickens through feeding experiments. The results showed that the skeletal muscle characteristics of AA after microbiota transplantation tended to be consistent with that of JY, as the fiber diameter was significantly increased, and glucose metabolism level was significantly enhanced in the pectoralis muscle. L. plantarum, L. ingluviei, L. salivarius, and their mixture could increase the production of the microbial metabolites protoporphyrin IX and short-chain fatty acids, therefore increasing the expression levels of genes related to the oxidative fiber type (MyHC SM and MyHC FRM), mitochondrial function (Tfam and CoxVa), and glucose metabolism (PFK, PK, PDH, IDH, and SDH), thereby increasing the fiber diameter and density. These three Lactobacillus species could be promising probiotics to improve the meat quality of chicken.IMPORTANCEThis study revealed that the L. plantarum, L. ingluviei, and L. salivarius could enhance the production of protoporphyrin IX and short-chain fatty acids in the cecum of chickens, improving glucose metabolism, and finally cause the increase in fiber diameter and density of skeletal muscle. These three microbes could be potential probiotic candidates to regulate glucose metabolism in skeletal muscle to improve the meat quality of chicken in broiler production.}, }
@article {pmid38780265, year = {2024}, author = {Zheng, L and Jiao, Y and Zhong, H and Tan, Y and Yin, Y and Liu, Y and Liu, D and Wu, M and Wang, G and Huang, J and Wang, P and Qin, M and Wang, M and Xiao, Y and Lv, T and Luo, Y and Hu, H and Hou, S-T and Kui, L}, title = {Human-derived fecal microbiota transplantation alleviates social deficits of the BTBR mouse model of autism through a potential mechanism involving vitamin B6 metabolism.}, journal = {mSystems}, volume = {9}, number = {6}, pages = {e0025724}, pmid = {38780265}, issn = {2379-5077}, support = {SZSM202103007//The Sanming Project of Medicine in Shenzhen Nanshan/ ; NSZD2023046//Major Program of Shenzhen Nanshan/ ; 81871026//MOST | National Natural Science Foundation of China (NSFC)/ ; 32371029//MOST | National Natural Science Foundation of China (NSFC)/ ; 2023SHIBS0002//the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions/ ; B2301001//Shenzhen Medical Research Fund/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; Mice ; Humans ; *Disease Models, Animal ; *Vitamin B 6/metabolism ; Gastrointestinal Microbiome ; Male ; Social Behavior ; Autism Spectrum Disorder/therapy/metabolism/microbiology ; Autistic Disorder/therapy/metabolism/microbiology ; }, abstract = {Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficiencies and stereotypic behaviors influenced by hereditary and/or environmental risk factors. There are currently no approved medications for treating the core symptoms of ASD. Human fecal microbiota transplantation (FMT) has emerged as a potential intervention to improve autistic symptoms, but the underlying mechanisms are not fully understood. In this study, we evaluated the effects of human-derived FMT on behavioral and multi-omics profiles of the BTBR mice, an established model for ASD. FMT effectively alleviated the social deficits in the BTBR mice and normalized their distinct plasma metabolic profile, notably reducing the elevated long-chain acylcarnitines. Integrative analysis linked these phenotypic changes to specific Bacteroides species and vitamin B6 metabolism. Indeed, vitamin B6 supplementation improved the social behaviors in BTBR mice. Collectively, these findings shed new light on the interplay between FMT and vitamin B6 metabolism and revealed a potential mechanism underlying the therapeutic role of FMT in ASD.IMPORTANCEAccumulating evidence supports the beneficial effects of human fecal microbiota transplantation (FMT) on symptoms associated with autism spectrum disorder (ASD). However, the precise mechanism by which FMT induces a shift in the microbiota and leads to symptom improvement remains incompletely understood. This study integrated data from colon-content metagenomics, colon-content metabolomics, and plasma metabolomics to investigate the effects of FMT treatment on the BTBR mouse model for ASD. The analysis linked the amelioration of social deficits following FMT treatment to the restoration of mitochondrial function and the modulation of vitamin B6 metabolism. Bacterial species and compounds with beneficial roles in vitamin B6 metabolism and mitochondrial function may further contribute to improving FMT products and designing novel therapies for ASD treatment.}, }
@article {pmid38779440, year = {2024}, author = {Kasapoglu, M and Yadavalli, R and Nawaz, S and Althwanay, A and AlEdani, EM and Kaur, H and Butt, S}, title = {The Impact of Microbiome Interventions on the Progression and Severity of Inflammatory Bowel Disease: A Systematic Review.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e60786}, pmid = {38779440}, issn = {2168-8184}, abstract = {Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation. The dysbiotic gut microbiome likely contributes to IBD pathogenesis. Microbiome-directed therapies such as fecal microbiota transplantation (FMT), probiotics, and synbiotics may help induce and maintain remission. This systematic review aimed to determine the efficacy of microbiome interventions compared to standard therapy or placebo for IBD treatment. PubMed, EMBASE, Cochrane CENTRAL, and Web of Science were searched for randomized controlled trials on microbiome interventions in IBD from inception to October 2023. The risk of bias was assessed using Cochrane tools. Outcomes included disease activity, endoscopy, histology, quality of life, and adverse events. A total of 18 randomized controlled trials were included. Three trials found intensive (i.e., high frequency of administration and/or large volumes of fecal material) multi-donor FMT superior to autologous FMT or glucocorticoids for UC remission induction. Seven placebo-controlled trials demonstrated higher remission rates with FMT, especially intensive protocols, versus control for mild-to-moderate UC. However, a single FMT did not prevent relapses. Seven probiotic trials showed the potential to improve UC activity and maintain remission. One synbiotic trial reported reduced inflammation and symptoms versus placebo. Serious adverse events were rare. Small sample sizes and protocol heterogeneity limited the conclusions. Current evidence indicates the potential benefits of microbiome interventions, particularly intensive multi-donor FMT, for inducing and maintaining remission in UC. Probiotics may also improve outcomes. Adequately powered trials using standardized protocols are still needed to firmly establish efficacy and safety. Microbiome-directed therapies represent a promising approach for improving IBD outcomes.}, }
@article {pmid38778483, year = {2024}, author = {Yan, J and Chen, H and Zhang, Y and Peng, L and Wang, Z and Lan, X and Yu, S and Yang, Y}, title = {Fecal microbiota transplantation significantly improved respiratory failure of amyotrophic lateral sclerosis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2353396}, pmid = {38778483}, issn = {1949-0984}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/microbiology ; Bacteroides ; Faecalibacterium prausnitzii ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Respiration, Artificial ; *Respiratory Insufficiency/therapy/microbiology ; Treatment Outcome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to respiratory failure, and eventually death. However, there is a lack of effective treatments for ALS. Here we report the results of fecal microbiota transplantation (FMT) in two patients with late-onset classic ALS with a Japan ALS severity classification of grade 5 who required tracheostomy and mechanical ventilation. In both patients, significant improvements in respiratory function were observed following two rounds of FMT, leading to weaning off mechanical ventilation. Their muscle strength improved, allowing for assisted standing and mobility. Other notable treatment responses included improved swallowing function and reduced muscle fasciculations. Metagenomic and metabolomic analysis revealed an increase in beneficial Bacteroides species (Bacteroides stercoris, Bacteroides uniformis, Bacteroides vulgatus), and Faecalibacterium prausnitzii after FMT, as well as elevated levels of metabolites involved in arginine biosynthesis and decreased levels of metabolites involved in branched-chain amino acid biosynthesis. These findings offer a potential rescue therapy for ALS with respiratory failure and provide new insights into ALS in general.}, }
@article {pmid38778379, year = {2024}, author = {Xu, W and Li, Y and Liu, L and Xie, J and Hu, Z and Kuang, S and Fu, X and Li, B and Sun, T and Zhu, C and He, Q and Sheng, W}, title = {Icaritin-curcumol activates CD8[+] T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {43}, number = {1}, pages = {149}, pmid = {38778379}, issn = {1756-9966}, support = {22B0370//Excellent Youth Project of Scientific Research Program of Hunan Education Department/ ; B2023034//Project of Traditional Chinese Medicine Administration of Hunan Province/ ; 2023JJ40511//Natural Science Foundation of Hunan Province/ ; kq2208204//Changsha Natural Science Foundation/ ; Z2023XJYQ05//Excellent Youth Project of Hunan University of Chinese Medicine/ ; W20243165//Hunan Provincial Hygiene and Health Commission Health Research Project/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; Male ; *DNA (Cytosine-5-)-Methyltransferase 1/metabolism ; Humans ; *CD8-Positive T-Lymphocytes/metabolism/immunology ; *Prostatic Neoplasms/metabolism/pathology/drug therapy ; Insulin-Like Growth Factor Binding Protein 2/metabolism ; Flavonoids/pharmacology/therapeutic use ; Disease Models, Animal ; }, abstract = {BACKGROUND: Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa.<br><br>METHODS: A mouse subcutaneous RM-1 cell tumor model was established. 16&#xa0;S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development.<br><br>RESULTS: After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3[+]CD8[+]IFN-&#x3b3;, CD3[+]CD8[+]Ki67 cells, and the levels of IFN-&#x3b3; and IFN-&#x3b1; in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2.<br><br>CONCLUSIONS: ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.}, }
@article {pmid38777572, year = {2024}, author = {}, title = {Puerarin alleviates atherosclerosis via the inhibition of Prevotella copri and its trimethylamine production.}, journal = {Gut}, volume = {73}, number = {12}, pages = {1934-1943}, doi = {10.1136/gutjnl-2024-331880}, pmid = {38777572}, issn = {1468-3288}, mesh = {Animals ; *Isoflavones/pharmacology/therapeutic use ; *Methylamines/metabolism/blood ; Mice ; *Atherosclerosis/prevention &amp; control/metabolism/drug therapy ; Humans ; *Prevotella/drug effects ; *Gastrointestinal Microbiome/drug effects ; Male ; Fecal Microbiota Transplantation ; Diet, High-Fat ; Disease Models, Animal ; Plaque, Atherosclerotic ; Female ; Middle Aged ; Mice, Knockout, ApoE ; }, abstract = {OBJECTIVE: Puerarin (PU) is a natural compound that exhibits limited oral bioavailability but has shown promise in the treatment of atherosclerosis (AS). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood. This study aimed to investigate the effects of PU and its mechanisms in mitigating AS in both mice and humans.<br><br>DESIGN: The impact of PU on AS was examined in ApoE [-/-] mice fed a high-fat diet (HFD) and in human patients with carotid artery plaque. To explore the causal link between PU-associated gut microbiota and AS, faecal microbiota transplantation (FMT) and mono-colonisation of mice with Prevotella copri (P. copri) were employed.<br><br>RESULTS: PU alleviated AS by modulating the gut microbiota, as evidenced by alterations in gut microbiota composition and the amelioration of AS following FMT from PU-treated mice into ApoE[-/-] mice fed HFD. Specifically, PU reduced the abundance of P. copri, which exacerbated AS by producing trimethylamine (TMA). Prolonged mono-colonisation of P. copri undermines the beneficial effects of PU on AS. In clinical, the plaque scores of AS patients were positively correlated with the abundance of P. copri and plasma trimethylamine-N-oxide (TMAO) levels. A 1-week oral intervention with PU effectively decreased P. copri levels and reduced TMAO concentrations in patients with carotid artery plaque.<br><br>CONCLUSION: PU may provide therapeutic benefits in combating AS by targeting P. copri and its production of TMA.<br><br>TRIAL REGISTRATION NUMBER: ChiCTR1900022488.}, }
@article {pmid38777056, year = {2024}, author = {He, G and Zhang, B and Yi, K and Chen, T and Shen, C and Cao, M and Wang, N and Zong, J and Wang, Y and Liu, K and Chang, F and Chen, X and Chen, L and Luo, Y and Meng, Y and Li, C and Zhou, X}, title = {Heat stress-induced dysbiosis of the gut microbiota impairs spermatogenesis by regulating secondary bile acid metabolism in the gut.}, journal = {The Science of the total environment}, volume = {937}, number = {}, pages = {173305}, doi = {10.1016/j.scitotenv.2024.173305}, pmid = {38777056}, issn = {1879-1026}, mesh = {*Dysbiosis ; Animals ; *Gastrointestinal Microbiome/physiology ; *Spermatogenesis/physiology ; Male ; *Bile Acids and Salts/metabolism ; Mice ; Cattle ; Heat-Shock Response/physiology ; Akkermansia/physiology ; Fecal Microbiota Transplantation ; Testis/metabolism ; }, abstract = {Heat stress (HS) poses a substantial challenge to livestock. Studies have demonstrated that HS reduces fertility and leads to gut microbiota dysbiosis in bulls. However, the impact of the gut microbiota on fertility in bulls during HS is still unclear. Our research revealed that HS exposure decreased semen quality in bulls, and fecal microbiota transplantation (FMT) from heat-stressed bulls to recipient mice resulted in a significant decrease in number of testicular germ cells and epididymal sperm. Untargeted metabolomics methodology and 16S rDNA sequencing conjoint analysis revealed that Akkermansia muciniphila (A. muciniphila) seemed to be a key bacterial regulator of spermatogenesis after HS exposure. Moreover, the research indicated that A. muciniphila regulated secondary bile acid metabolism by promoting the colonization of bile salt hydrolase (BSH)-metabolizing bacteria, leading to increase of retinol absorption in the host gut and subsequently elevation of testicular retinoic acid level, thereby improving spermatogenesis. This study sheds light on the relationship between HS-induced microbiota dysbiosis and spermatogenesis, offering a potential therapeutic approach for addressing bull spermatogenic dysfunction triggered by HS exposure.}, }
@article {pmid38772789, year = {2024}, author = {Marasco, G and Cremon, C and Barbaro, MR and Bianco, F and Stanghellini, V and Barbara, G}, title = {Microbiota modulation in disorders of gut-brain interaction.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {56}, number = {12}, pages = {1971-1979}, doi = {10.1016/j.dld.2024.05.004}, pmid = {38772789}, issn = {1878-3562}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; *Prebiotics ; *Brain-Gut Axis/physiology ; *Fecal Microbiota Transplantation ; *Irritable Bowel Syndrome/microbiology/therapy/physiopathology ; Constipation/therapy/microbiology ; Anti-Bacterial Agents/therapeutic use ; Dyspepsia/microbiology/therapy ; Dysbiosis/therapy ; }, abstract = {Disorders of gut-brain interaction (DGBI) are common chronic conditions characterized by persistent and recurring gastrointestinal symptoms triggered by several pathophysiological factors, including an altered gut microbiota. The most common DGBI are irritable bowel syndrome (IBS), functional constipation (FC) and functional dyspepsia (FD). Recently, a deep understanding of the role of the gut microbiota in these diseases was possible due to multi-omics methods capable to provide a comprehensive assessment. Most of the therapies recommended for these patients, can modulate the gut microbiota such as diet, prebiotics, probiotics and non-absorbable antibiotics, which were shown to be safe and effective. Since patients complain symptoms after food ingestion, diet represents the first line therapeutic approach. Avoiding dietary fat and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, and increasing the number of soluble fibers represent the therapeutic choices for FD, IBS and FC respectively. Probiotics, as a category, have been employed with good results in all the abovementioned DGBI. Rifaximin has been shown to be useful in the context of bowel related disorders, although a recent trial showed positive results for FD. Fecal microbiota transplantation has been tested for IBS and FC with promising results. In this review, we will briefly summarize the current understanding on dysbiosis and discuss microbiota modulation strategies to treat patients with DGBI.}, }
@article {pmid38772541, year = {2025}, author = {Xu, Z and Wang, S and Liu, C and Kang, J and Pan, Y and Zhang, Z and Zhou, H and Xu, M and Li, X and Wang, H and Niu, S and Liu, L and Sun, D and Liu, X}, title = {The Role of Gut Microbiota in Male Erectile Dysfunction of Rats.}, journal = {The world journal of men's health}, volume = {43}, number = {1}, pages = {213-227}, pmid = {38772541}, issn = {2287-4208}, support = {82171594/NNSFC/National Natural Science Foundation of China/China ; }, abstract = {PURPOSE: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function.<br><br>MATERIALS AND METHODS: Male Sprague-Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection.<br><br>RESULTS: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways.<br><br>CONCLUSIONS: Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.}, }
@article {pmid38770714, year = {2024}, author = {González-Correa, C and Moleón, J and Miñano, S and Robles-Vera, I and Toral, M and Barranco, AM and Martín-Morales, N and O'Valle, F and Guerra-Hernández, E and Sánchez, M and Gómez-Guzmán, M and Jiménez, R and Romero, M and Duarte, J}, title = {Differing contributions of the gut microbiota to the blood pressure lowering effects induced by first-line antihypertensive drugs.}, journal = {British journal of pharmacology}, volume = {181}, number = {18}, pages = {3420-3444}, doi = {10.1111/bph.16410}, pmid = {38770714}, issn = {1476-5381}, support = {//Agencia Estatal de Investigaci&#xf3;n (AEI)/ ; PID2020-116347RB-I00//Ministerio de Ciencia e Innovaci&#xf3;n (MCIN)/ ; CTS 164//Junta de Andaluc&#xed;a/ ; P20_00193//Junta de Andaluc&#xed;a/ ; A-CTS-318-UGR20//Junta de Andaluc&#xed;a/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Antihypertensive Agents/pharmacology ; Male ; *Rats, Inbred SHR ; *Rats, Inbred WKY ; Rats ; *Blood Pressure/drug effects ; *Amlodipine/pharmacology ; Captopril/pharmacology ; Hypertension/drug therapy/microbiology ; Hydrochlorothiazide/pharmacology ; Dysbiosis ; }, abstract = {BACKGROUND AND PURPOSE: This study analyses whether first-line antihypertensive drugs ameliorate the dysbiosis state in hypertension, and to test if this modification contributes to their blood pressure (BP) lowering properties in a genetic model of neurogenic hypertension.<br><br>EXPERIMENTAL APPROACH: Twenty-week-old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were untreated or treated with captopril, amlodipine or hydrochlorothiazide. A faecal microbiota transplantation (FMT) experiment was also performed by gavage of faecal content from donor SHR-treated groups to SHR recipients for 3&#x2009;weeks.<br><br>KEY RESULTS: Faeces from SHR showed gut dysbiosis, characterized by lower acetate- and higher lactate-producing bacteria and lower strict anaerobic bacteria. All three drugs increased the anaerobic bacteria proportion, captopril and amlodipine restored the proportion of acetate-producing bacterial populations to WKY levels, whereas hydrochlorothiazide decreased butyrate-producing bacteria. Captopril and amlodipine decreased gut pathology and permeability and attenuated sympathetic drive in the gut. Both drugs decreased neuroinflammation and oxidative stress in the hypothalamic paraventricular nuclei. Hydrochlorothiazide was unable to reduce neuroinflammation, gut sympathetic tone and gut integrity. FMT from SHR-amlodipine to SHR decreased BP, ameliorated aortic endothelium-dependent relaxation to acetylcholine, lowered NADPH oxidase activity, aortic Th17 infiltration and reduced neuroinflammation, whereas FMT from SHR-hydrochlorothiazide did not have these effects.<br><br>CONCLUSIONS AND IMPLICATIONS: First-line antihypertensive drugs induced different modifications of gut integrity and gut dysbiosis in SHR, which result in no contribution of microbiota in the BP lowering effects of hydrochlorothiazide, whereas the vasculo-protective effect induced by amlodipine involves gut microbiota reshaping and gut-immune system communication.}, }
@article {pmid38770226, year = {2024}, author = {Hayes, AG and Penny, MJ and Aivazian, K and Greenfield, JR}, title = {Acute Interstitial Nephritis and Oxalate Nephropathy After Rapid Pasireotide Response in Treatment-resistant Acromegaly.}, journal = {JCEM case reports}, volume = {2}, number = {5}, pages = {luae071}, pmid = {38770226}, issn = {2755-1520}, abstract = {We report a case of interstitial nephritis, likely secondary to oxalate nephropathy, due to the development of pancreatic exocrine dysfunction after commencement of pasireotide for acromegaly. Pasireotide is known to impair insulin secretion but can also impair pancreatic exocrine function, hypothezised to result from high-affinity binding of somatostatin receptors 1, 2, 3, and 5. This has been an advantage in postoperative tissue anastomoses after pancreatic surgery, but exocrine insufficiency has not been reported when used for the treatment of acromegaly. A 73-year-old woman, diagnosed with acromegaly, was unable to achieve biochemical control despite 2 surgical resections of an invasive mammosomatotroph pituitary tumor and treatment with cabergoline and maximal-dose lanreotide. The tumor expressed somatostatin receptor type 5 but not somatostatin receptor type 2, predicting good response from pasireotide, which was commenced at 40 mg every 4 weeks. IGF-1 rapidly normalized, but the patient presented with nausea, anorexia, and acute kidney injury. Renal biopsy revealed acute-on-chronic interstitial nephritis, with numerous oxalate crystals. Increased fecal fat globules were noted on fat stain (3+), supporting malabsorption as an etiology of secondary enteric hyperoxaluria. Renal function recovered to near baseline over months following pasireotide withdrawal and high-dose glucocorticoids.}, }
@article {pmid38770171, year = {2024}, author = {Cui, X and Zhang, T and Xie, T and Guo, FX and Zhang, YY and Deng, YJ and Wang, Q and Guo, YX and Dong, MH and Luo, XT}, title = {Research Progress on the Correlation Between Hypertension and Gut Microbiota.}, journal = {Journal of multidisciplinary healthcare}, volume = {17}, number = {}, pages = {2371-2387}, pmid = {38770171}, issn = {1178-2390}, abstract = {Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut-brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations.}, }
@article {pmid38767452, year = {2024}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Kazadi, D and Halaweish, H and Khan, MH and Hoeschen, A and Cao, Q and Luo, X and Kabage, AJ and Lopez, S and Ramamoorthy, S and Holtan, SG and Weisdorf, DJ and Khoruts, A and Staley, C}, title = {Multi-omics Analysis of a Fecal Microbiota Transplantation Trial Identifies Novel Aspects of Acute GVHD Pathogenesis.}, journal = {Cancer research communications}, volume = {4}, number = {6}, pages = {1454-1466}, pmid = {38767452}, issn = {2767-9764}, support = {KL2 TR002492/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; KL2TR002492//Foundation for the National Institutes of Health (FNIH)/ ; UL1TR002494//Foundation for the National Institutes of Health (FNIH)/ ; P30CA07759//HHS | NIH | National Cancer Institute (NCI)/ ; Chainbreaker grant//UMN | Clinical and Translational Science Institute, University of Minnesota (CTSI)/ ; n/a//Achieving Cures Together/ ; }, mesh = {Humans ; *Graft vs Host Disease/microbiology/immunology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Male ; Female ; Middle Aged ; *Hematopoietic Stem Cell Transplantation/methods/adverse effects ; Adult ; Leukemia, Myeloid, Acute/therapy/microbiology/immunology ; Transplantation, Homologous/methods/adverse effects ; Faecalibacterium ; Aged ; Acute Disease ; Feces/microbiology ; Metabolome ; Multiomics ; }, abstract = {UNLABELLED: Acute GVHD (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) associated with gut microbiota disruptions. However, whether therapeutic microbiota modulation prevents aGVHD is unknown. We conducted a randomized, placebo-controlled trial of third-party fecal microbiota transplantation (FMT) administered at the peak of microbiota injury in 100 patients with acute myeloid leukemia receiving induction chemotherapy and alloHCT recipients. Despite improvements in microbiome diversity, expansion of commensals, and shrinkage of potential pathogens, aGVHD occurred more frequently after FMT than placebo. Although this unexpected finding could be explained by clinical differences between the two arms, we asked whether a microbiota explanation might be also present. To this end, we performed multi-omics analysis of preintervention and postintervention gut microbiome and serum metabolome. We found that postintervention expansion of Faecalibacterium, a commensal genus with gut-protective and anti-inflammatory properties under homeostatic conditions, predicted a higher risk for aGVHD. Faecalibacterium expansion occurred predominantly after FMT and was due to engraftment of unique donor taxa, suggesting that donor Faecalibacterium-derived antigens might have stimulated allogeneic immune cells. Faecalibacterium and ursodeoxycholic acid (an anti-inflammatory secondary bile acid) were negatively correlated, offering an alternative mechanistic explanation. In conclusion, we demonstrate context dependence of microbiota effects where a normally beneficial bacteria may become detrimental in disease. While FMT is a broad, community-level intervention, it may need precision engineering in ecologically complex settings where multiple perturbations (e.g., antibiotics, intestinal damage, alloimmunity) are concurrently in effect.<br><br>SIGNIFICANCE: Post-FMT expansion of Faecalibacterium, associated with donor microbiota engraftment, predicted a higher risk for aGVHD in alloHCT recipients. Although Faecalibacterium is a commensal genus with gut-protective and anti-inflammatory properties under homeostatic conditions, our findings suggest that it may become pathogenic in the setting of FMT after alloHCT. Our results support a future trial with precision engineering of the FMT product used as GVHD prophylaxis after alloHCT.}, }
@article {pmid38765739, year = {2024}, author = {Davoutis, E and Gkiafi, Z and Lykoudis, PM}, title = {Bringing gut microbiota into the spotlight of clinical research and medical practice.}, journal = {World journal of clinical cases}, volume = {12}, number = {14}, pages = {2293-2300}, pmid = {38765739}, issn = {2307-8960}, abstract = {Despite the increasing scientific interest and expanding role of gut microbiota (GM) in human health, it is rarely reported in case reports and deployed in clinical practice. Proteins and metabolites produced by microbiota contribute to immune system development, energy homeostasis and digestion. Exo- and endogenous factors can alter its composition. Disturbance of microbiota, also known as dysbiosis, is associated with various pathological conditions. Specific bacterial taxa and related metabolites are involved in disease pathogenesis and therefore can serve as a diagnostic tool. GM could also be a useful prognostic factor by predicting future disease onset and preventing hospital-associated infections. Additionally, it can influence response to treatments, including those for cancers, by altering drug bioavailability. A thorough understanding of its function has permitted significant development in therapeutics, such as probiotics and fecal transplantation. Hence, GM should be considered as a ground-breaking biological parameter, and it is advisable to be investigated and reported in literature in a more consistent and systematic way.}, }
@article {pmid38761425, year = {2024}, author = {Tian, R and Wang, X and Tang, S and Zhao, L and Hao, Y and Li, R and Zhou, X}, title = {Gut microbiota mediates the protective effects of β-hydroxybutyrate against cisplatin-induced acute kidney injury.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {175}, number = {}, pages = {116752}, doi = {10.1016/j.biopha.2024.116752}, pmid = {38761425}, issn = {1950-6007}, mesh = {Animals ; *Cisplatin/adverse effects ; *Gastrointestinal Microbiome/drug effects ; *Acute Kidney Injury/chemically induced/prevention &amp; control ; Male ; *Dysbiosis/chemically induced ; *Mice, Inbred C57BL ; Mice ; *3-Hydroxybutyric Acid/pharmacology ; Kidney/drug effects ; Fecal Microbiota Transplantation ; Diet, High-Fat/adverse effects ; NF-kappa B/metabolism ; Toll-Like Receptor 4/metabolism ; Protective Agents/pharmacology ; Anti-Bacterial Agents/pharmacology/adverse effects ; Antineoplastic Agents/adverse effects/toxicity ; }, abstract = {The gut microbiota has been reported to be perturbed by chemotherapeutic agents and to modulate side effects. However, the critical role of β-hydroxybutyrate (BHB) in the regulation of the gut microbiota and the pathogenesis of chemotherapeutic agents related nephrotoxicity remains unknown. We conducted a comparative analysis of the composition and function of gut microbiota in healthy, cisplatin-challenged, BHB-treated, and high-fat diet-treated mice using 16 S rDNA gene sequencing. To understand the crucial involvement of intestinal flora in BHB's regulation of cisplatin -induced nephrotoxicity, we administered antibiotics to deplete the gut microbiota and performed fecal microbiota transplantation (FMT) before cisplatin administration. 16 S rDNA gene sequencing analysis demonstrated that both endogenous and exogenous BHB restored gut microbiota dysbiosis and cisplatin-induced intestinal barrier disruption in mice. Additionally, our findings suggested that the LPS/TLR4/NF-κB pathway was responsible for triggering renal inflammation in the gut-kidney axis. Furthermore, the ablation of the gut microbiota ablation using antibiotics eliminated the renoprotective effects of BHB against cisplatin-induced acute kidney injury. FMT also confirmed that administration of BHB-treated gut microbiota provided protection against cisplatin-induced nephrotoxicity. This study elucidated the mechanism by which BHB affects the gut microbiota mediation of cisplatin-induced nephrotoxicity by inhibiting the inflammatory response, which may help develop novel therapeutic approaches that target the composition of the microbiota.}, }
@article {pmid38759313, year = {2024}, author = {Xu, D and Liu, D and Jiang, N and Xie, Y and He, D and Cheng, J and Liu, J and Fu, S and Hu, G}, title = {Narirutin mitigates dextrose sodium sulfate-induced colitis in mice by modulating intestinal flora.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {130}, number = {}, pages = {155730}, doi = {10.1016/j.phymed.2024.155730}, pmid = {38759313}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; Male ; *Colon/drug effects/pathology ; *Mice, Inbred C57BL ; Glucose/metabolism ; Colitis, Ulcerative/chemically induced/drug therapy ; Dextran Sulfate ; Flavanones/pharmacology ; Anti-Inflammatory Agents/pharmacology ; Disease Models, Animal ; NF-kappa B/metabolism ; Fecal Microbiota Transplantation ; Colitis/chemically induced/drug therapy ; Citrus/chemistry ; Tight Junction Proteins/metabolism ; Sulfates/pharmacology ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a prolonged inflammatory disease of the gastrointestinal tract. Current therapeutic options remain limited, underscoring the imperative to explore novel therapeutic strategies. Narirutin (NR), a flavonoid naturally present in citrus fruits, exhibits excellent anti-inflammatory effects in vitro, yet its in vivo efficacy, especially in UC, remains underexplored.<br><br>OBJECTIVE: This work examined the effect of NR on dextrose sodium sulfate (DSS)-induced UC in mice in vivo, with a specific focus on the role of gut flora in it.<br><br>METHODS: The effects of NR (10, 20, and 40 mg/kg) on DSS-induced UC in mice were investigated by monitoring changes in body weight, disease activity index (DAI) scores, colon length, and histological damage. Colonic levels of pro-inflammatory mediators, tight junction (TJ) proteins, and inflammation-related signaling pathway proteins were analyzed via enzyme-linked immunosorbent assay, western blot, and immunofluorescence. The role of gut microbiota in NR against colitis was analyzed through 16S rRNA sequencing, flora clearance assays, and fecal microbiota transplantation (FMT) assays.<br><br>RESULTS: NR administration suppressed DSS-induced colitis as reflected in a decrease in body weight loss, DAI score, colon length shortening, and histological score. Furthermore, NR administration preserved the integrity of the DSS-induced intestinal barrier by inhibiting the reduction of TJ proteins (claudin3, occludin, and zonula occludens-1). Moreover, NR administration markedly repressed the activation of the toll-like receptor 4-mitogen-activated protein kinase/nuclear factor-&#x3ba;B pathway and reduced the amount of pro-inflammatory mediators in the colon. Importantly, the results of 16S rRNA sequencing showed that the intestinal flora of mice with colitis exhibited richer microbial diversity following NR administration, with elevated abundance of Lactobacillaceae (Lactobacillus) and decreased abundance of Bacteroidaceae (Bacteroides) and Shigella. In addition, the anti-colitis effect of NR almost disappeared after gut flora clearance. Further FMT assay also validated this gut flora-dependent protective mechanism of NR.<br><br>CONCLUSION: Our findings suggest that NR is a prospective natural compound for the management of UC by modulating intestinal flora.}, }
@article {pmid38758227, year = {2024}, author = {Long, C and Zhang, C and Xie, Y}, title = {Study on the mechanism of hirudin multi target delaying renal function decline in chronic kidney disease based on the "gut-kidney axis" theory.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {397}, number = {10}, pages = {7951-7962}, pmid = {38758227}, issn = {1432-1912}, support = {82060804//2020 National Natural Science Foundation Project/ ; 2023GXNSFAA026212//2023 Guangxi Natural Science Foundation Program/ ; 2022MS010//2022 Guangxi University of Traditional Chinese Medicine (GXUTCM) School-level Surface Projects/ ; }, mesh = {Animals ; *Renal Insufficiency, Chronic/drug therapy/metabolism/microbiology ; *Hirudins/pharmacology ; Male ; *Kidney/drug effects/metabolism/pathology ; *Rats, Sprague-Dawley ; *Gastrointestinal Microbiome/drug effects ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Rats ; Disease Models, Animal ; Occludin/metabolism ; Claudin-1/metabolism/genetics ; Colon/drug effects/metabolism/pathology ; }, abstract = {The disorder of the "gut-kidney axis" exacerbates renal function decline in chronic kidney disease (CKD), and current CKD therapy is insufficient to address this issue. Hirudin has a palliative effect on the decline of renal function. However, whether hirudin can delay CKD by regulating the "intestinal renal axis" disorder remains unclear. Unilateral ureteral ligation (UUO) induced CKD rat model, and the rats were treated with bifidobacterium and hirudin for 36 days. After 14 and 36 days of modeling, kidney and colon tissues were collected for pathology, western blot (WB) assay, and quantitative real-time PCR (qPCR) detection. Serum samples were collected for renal function testing. Fecal samples were used for 16S rRNA sequencing and research on fecal bacterial transplantation. Lipopolysaccharide combine with adenosine 5'-triphosphate (LPS + ATP)-induced intestinal epithelial cell injury was treated with a nod-like receptor pyrin domain-associated protein 3 (NLRP3) inhibitor and hirudin. Protein expression was detected using WB and qPCR. The kidneys and colons of the CKD rats exhibited varying degrees of lesions. Creatinine (CRE), blood urea nitrogen (BUN), N-acetyl-β-D-glucosidase (NAG) enzyme, and serum uremic toxins were elevated. The expression of claudin-1 and occludin was decreased, NLRP3 inflammatory-related proteins were increased, and the gut microbiota was disrupted. These pathological changes were more pronounced after 36 days of modeling. Meanwhile, high-dose hirudin treatment significantly improved these lesions and restored the intestinal flora to homeostasis in CKD rats. In vitro, hirudin demonstrated comparable effects to NLRP3 inhibitors by upregulating claudin-1 and occludin expression, and downregulating NLRP3 inflammatory-related proteins expression. The dysbiosis of the gut microbiota and impaired intestinal epithelial barrier function in CKD are associated with renal dysfunction in CKD. Hirudin delays the progression of CKD by regulating the disorder of the "gut-kidney axis" and inhibiting the activation of the NLRP3-ASC-caspase-1 pathway.}, }
@article {pmid38757304, year = {2024}, author = {Wu, P and Xue, J and Zhu, Z and Yu, Y and Sun, Q and Xie, M and Wang, B and Huang, P and Feng, Z and Zhao, J}, title = {Puerariae lobatae Radix ameliorates chronic kidney disease by reshaping gut microbiota and downregulating Wnt/β‑catenin signaling.}, journal = {Molecular medicine reports}, volume = {30}, number = {1}, pages = {}, pmid = {38757304}, issn = {1791-3004}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Renal Insufficiency, Chronic/drug therapy/metabolism ; *Wnt Signaling Pathway/drug effects ; Mice ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Male ; *Pueraria/chemistry ; Disease Models, Animal ; Dysbiosis/drug therapy ; Down-Regulation/drug effects ; Kidney/drug effects/pathology/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; }, abstract = {Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote the gut microbiota homeostasis; however, its role in renoprotection remains unknown. The present study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8‑week 2% NaCl‑feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, The medium and high doses of PLR significantly alleviated CKD‑associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and downregulating the canonical Wnt/β‑catenin pathway. Furthermore, PLR rescued the gut microbiota dysbiosis and protected against high salt‑induced gut barrier dysfunction. Enrichment of Akkermansia and Bifidobacterium was found after PLR intervention, the relative abundances of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was, at least partially, exerted through gut microbiota reestablishment and downregulation of the Wnt/β‑catenin pathway. The present study provided evidence for a new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.}, }
@article {pmid38754739, year = {2024}, author = {Allegretti, JR and Khanna, S and Mullish, BH and Feuerstadt, P}, title = {The Progression of Microbiome Therapeutics for the Management of Gastrointestinal Diseases and Beyond.}, journal = {Gastroenterology}, volume = {167}, number = {5}, pages = {885-902}, doi = {10.1053/j.gastro.2024.05.004}, pmid = {38754739}, issn = {1528-0012}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; *Gastrointestinal Diseases/microbiology/therapy ; Liver Diseases/microbiology/therapy ; Precision Medicine/methods ; Dysbiosis/therapy/microbiology ; Animals ; Treatment Outcome ; }, abstract = {There has been an increased ability to investigate the human microbiota through next-generation sequencing and functional assessment. This advancement has rapidly expanded our ability to study and manipulate the gastrointestinal microbiome to mitigate disease. Fecal microbiota transplantation, a therapy that broadly transfers the entire intestinal ecosystem, has been explored as a potential therapeutic in a variety of gastrointestinal, hepatic, and extraintestinal conditions. The field, however, continues to evolve, with a movement toward precision microbiome therapeutics, individualizing care for various disorders. This review will describe the use of fecal microbiota transplantation, microbiota restoration, and precision microbiome therapeutics, focusing on gastrointestinal and hepatic diseases.}, }
@article {pmid38754198, year = {2024}, author = {Liu, JL and Chen, LJ and Liu, Y and Li, JH and Zhang, KK and Hsu, C and Li, XW and Yang, JZ and Chen, L and Zeng, JH and Xie, XL and Wang, Q}, title = {The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.}, journal = {Ecotoxicology and environmental safety}, volume = {279}, number = {}, pages = {116457}, doi = {10.1016/j.ecoenv.2024.116457}, pmid = {38754198}, issn = {1090-2414}, mesh = {Animals ; *Methamphetamine/toxicity ; Male ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Testis/drug effects/pathology ; *Reproduction/drug effects ; Spermatozoa/drug effects ; Mice, Inbred C57BL ; Central Nervous System Stimulants/toxicity ; Fecal Microbiota Transplantation ; }, abstract = {Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.}, }
@article {pmid38753616, year = {2024}, author = {Pidala, J and Carpenter, PA and Onstad, L and Pavletic, SZ and Hamilton, BK and Chen, GL and Farhadfar, N and Hall, M and Lee, SJ}, title = {Study protocol: Close Assessment and Testing for Chronic Graft-vs.-Host disease (CATCH).}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0298026}, pmid = {38753616}, issn = {1932-6203}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Biomarkers ; Chronic Disease ; *Graft vs Host Disease/diagnosis/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Longitudinal Studies ; Prospective Studies ; Transplantation, Homologous ; Multicenter Studies as Topic ; }, abstract = {Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that causes significant late morbidity and mortality following allogeneic hematopoietic cell transplantation. The "Close Assessment and Testing for Chronic GVHD (CATCH)" study is a multi-center Chronic GVHD Consortium prospective, longitudinal cohort study designed to enroll patients before hematopoietic cell transplantation and follow them closely to capture the development of chronic GVHD and to identify clinical and biologic biomarkers of chronic GVHD onset. Data are collected pre-transplant and every two months through one-year post-transplant with chart review thereafter. Evaluations include clinician assessment of chronic GVHD and its manifestations, patient-reported outcomes, multiple biospecimens (blood, saliva, tears, buccal mucosa and fecal samples, biopsies of skin and mouth), laboratory testing, and medical record abstraction. This report describes the rationale, design, and methods of the CATCH study, and invites collaboration with other investigators to leverage this resource. trial registration: This study is registered at www.clinicaltrials.gov as NCT04188912.}, }
@article {pmid38752739, year = {2024}, author = {Anderson, BG and Raskind, A and Hissong, R and Dougherty, MK and McGill, SK and Gulati, AS and Theriot, CM and Kennedy, RT and Evans, CR}, title = {Offline Two-Dimensional Liquid Chromatography-Mass Spectrometry for Deep Annotation of the Fecal Metabolome Following Fecal Microbiota Transplantation.}, journal = {Journal of proteome research}, volume = {23}, number = {6}, pages = {2000-2012}, doi = {10.1021/acs.jproteome.4c00022}, pmid = {38752739}, issn = {1535-3907}, support = {U2C ES030164/ES/NIEHS NIH HHS/United States ; P41 GM108538/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Feces/microbiology/chemistry ; Chromatography, Liquid/methods ; *Metabolome ; *Fecal Microbiota Transplantation ; *Metabolomics/methods ; *Tandem Mass Spectrometry/methods ; Clostridium Infections/microbiology/metabolism ; Clostridioides difficile/metabolism ; Bile Acids and Salts/metabolism/analysis ; Liquid Chromatography-Mass Spectrometry ; }, abstract = {Biological interpretation of untargeted LC-MS-based metabolomics data depends on accurate compound identification, but current techniques fall short of identifying most features that can be detected. The human fecal metabolome is complex, variable, incompletely annotated, and serves as an ideal matrix to evaluate novel compound identification methods. We devised an experimental strategy for compound annotation using multidimensional chromatography and semiautomated feature alignment and applied these methods to study the fecal metabolome in the context of fecal microbiota transplantation (FMT) for recurrent C. difficile infection. Pooled fecal samples were fractionated using semipreparative liquid chromatography and analyzed by an orthogonal LC-MS/MS method. The resulting spectra were searched against commercial, public, and local spectral libraries, and annotations were vetted using retention time alignment and prediction. Multidimensional chromatography yielded more than a 2-fold improvement in identified compounds compared to conventional LC-MS/MS and successfully identified several rare and previously unreported compounds, including novel fatty-acid conjugated bile acid species. Using an automated software-based feature alignment strategy, most metabolites identified by the new approach could be matched to features that were detected but not identified in single-dimensional LC-MS/MS data. Overall, our approach represents a powerful strategy to enhance compound identification and biological insight from untargeted metabolomics data.}, }
@article {pmid38752578, year = {2024}, author = {Fuhri Snethlage, CM and de Wit, D and Wortelboer, K and Rampanelli, E and Hanssen, NMJ and Nieuwdorp, M}, title = {Can fecal microbiota transplantations modulate autoimmune responses in type 1 diabetes?.}, journal = {Immunological reviews}, volume = {325}, number = {1}, pages = {46-63}, doi = {10.1111/imr.13345}, pmid = {38752578}, issn = {1600-065X}, support = {101141346//ERC advanced grant FATGAP/ ; 2021T055//Dekker grant of Dutch Heart Foundation/ ; 2020.10.002//Stichting Diabetes Onderzoek Nederland/ ; 09150172210019/ZONMW_/ZonMw/Netherlands ; 09150172210050/ZONMW_/ZonMw/Netherlands ; 09150182010020/ZONMW_/ZonMw/Netherlands ; }, mesh = {*Diabetes Mellitus, Type 1/immunology/microbiology/therapy ; Humans ; Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; *Autoimmunity ; *Disease Models, Animal ; Mice ; }, abstract = {Type 1 diabetes (T1D) is a chronic autoimmune disease targeting insulin-producing pancreatic beta cells. T1D is a multifactorial disease incorporating genetic and environmental factors. In recent years, the advances in high-throughput sequencing have allowed researchers to elucidate the changes in the gut microbiota taxonomy and functional capacity that accompany T1D development. An increasing number of studies have shown a role of the gut microbiota in mediating immune responses in health and disease, including autoimmunity. Fecal microbiota transplantations (FMT) have been largely used in murine models to prove a causal role of the gut microbiome in disease progression and have been shown to be a safe and effective treatment in inflammatory human diseases. In this review, we summarize and discuss recent research regarding the gut microbiota-host interactions in T1D, the current advancement in therapies for T1D, and the usefulness of FMT studies to explore microbiota-host immunity encounters in murine models and to shape the course of human type 1 diabetes.}, }
@article {pmid38750621, year = {2024}, author = {Hain, E and Lefèvre, JH and Ricardo, A and Lee, S and Zaghiyan, K and McLemore, E and Sherwinter, D and Rhee, R and Wilson, M and Martz, J and Maykel, J and Marks, J and Marcet, J and Rouanet, P and Maggiori, L and Komen, N and De Hous, N and Lakkis, Z and Tuech, JJ and Attiyeh, F and Cotte, E and Sylla, P}, title = {SafeHeal Colovac Colorectal Anastomosis Protection Device evaluation (SAFE-2) pivotal study: an international randomized controlled study to evaluate the safety and effectiveness of the Colovac Colorectal Anastomosis Protection Device.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {26}, number = {6}, pages = {1271-1284}, doi = {10.1111/codi.17012}, pmid = {38750621}, issn = {1463-1318}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Anastomosis, Surgical/instrumentation/adverse effects/methods ; *Anastomotic Leak/prevention &amp; control ; *Colon/surgery ; Ileostomy/instrumentation/adverse effects/methods ; Postoperative Complications/prevention &amp; control ; Proctectomy/adverse effects/methods/instrumentation ; Prospective Studies ; Quality of Life ; *Rectal Neoplasms/surgery ; *Rectum/surgery ; Treatment Outcome ; }, abstract = {AIM: Although proximal faecal diversion is standard of care to protect patients with high-risk colorectal anastomoses against septic complications of anastomotic leakage, it is associated with significant morbidity. The Colovac device (CD) is an intraluminal bypass device intended to avoid stoma creation in patients undergoing low anterior resection. A preliminary study (SAFE-1) completed in three European centres demonstrated 100% protection of colorectal anastomoses in 15 patients, as evidenced by the absence of faeces below the CD. This phase III trial (SAFE-2) aims to evaluate the safety and effectiveness of the CD in a larger cohort of patients undergoing curative rectal cancer resection.<br><br>METHODS: SAFE-2 is a pivotal, multicentre, prospective, open-label, randomized, controlled trial. Patients will be randomized in a 1:1 ratio to either the CD arm or the diverting loop ileostomy arm, with a recruitment target of 342 patients. The co-primary endpoints are the occurrence of major postoperative complications within 12&#x2009;months of index surgery and the effectiveness of the CD in reducing stoma creation rates. Data regarding quality of life and patient's acceptance and tolerance of the device will be collected.<br><br>DISCUSSION: SAFE-2 is a multicentre randomized, control trial assessing the efficacy and the safety of the CD in protecting low colorectal anastomoses created during oncological resection relative to standard diverting loop ileostomy.<br><br>TRIAL REGISTRATION: NCT05010850.}, }
@article {pmid38749910, year = {2024}, author = {Cheng, CL and Wang, XJ and Fan, LX and Lv, YL and Xiong, K and Jiang, ZW and Gan, T and Fu, G}, title = {Successful allogeneic fecal microbiota transplantation for severe diversion colitis: a case report.}, journal = {The Journal of international medical research}, volume = {52}, number = {5}, pages = {3000605241241000}, pmid = {38749910}, issn = {1473-2300}, mesh = {Humans ; Male ; Aged ; *Fecal Microbiota Transplantation/methods ; *Colitis/microbiology/therapy ; *Ileostomy ; *Gastrointestinal Microbiome ; Transplantation, Homologous/methods ; Treatment Outcome ; Colonoscopy ; }, abstract = {Ileostomy diverts the flow of feces, which can result in malnutrition in the distal part of the intestine. The diversity of the gut microbiota consequently decreases, ultimately leading to intestinal dysbiosis and dysfunction. This condition can readily result in diversion colitis (DC). Potential treatment strategies include interventions targeting the gut microbiota. In this case study, we effectively treated a patient with severe DC by ileostomy and allogeneic fecal microbiota transplantation (FMT). A 69-year-old man presented with a perforated malignant tumor in the descending colon and an iliac abscess. He underwent laparoscopic radical sigmoid colon tumor resection and prophylactic ileostomy. Follow-up colonoscopy 3 months postoperatively revealed diffuse intestinal mucosal congestion and edema along with granular inflammatory follicular hyperplasia, leading to a diagnosis of severe DC. After two rounds of allogeneic FMT, both the intestinal mucosal bleeding and edema significantly improved, as did the diversity of the gut microbiota. The positive outcome of allogeneic FMT in this case highlights the potential advantages that this procedure can offer patients with DC. However, few studies have focused on allogeneic FMT, and more in-depth research is needed to gain a better understanding.}, }
@article {pmid38749861, year = {2024}, author = {Galvao, FHF}, title = {Microsurgical Technique and Results of Anorectal Transplantation in the Rat.}, journal = {Transplantation proceedings}, volume = {56}, number = {5}, pages = {1138-1140}, doi = {10.1016/j.transproceed.2024.03.025}, pmid = {38749861}, issn = {1873-2623}, mesh = {Animals ; Rats ; *Anal Canal/transplantation ; Anastomosis, Surgical ; Fecal Incontinence/surgery/etiology ; Graft Rejection ; *Microsurgery/methods ; *Rectum/transplantation ; }, abstract = {UNLABELLED: Anorectal transplantation (ART) is an obvious therapeutic option for treating permanent colostomy and severe fecal incontinence. The rat is the best model for beginning studies of a new surgical procedure. In this article, we review ART techniques in rats.<br><br>METHODS: We reviewed articles on rat and ART keywords throughout Cochrane Library, MEDLINE, and EMBASE. Five articles were found, of which 2 used autotransplantations, 1 performed only transplantation of the anal canal and extraperitoneal rectum, and another performed transplantation of the entire intestine, including the anus, but only followed for 2 hours.<br><br>RESULTS: In 2016, we performed the first series of isoART (n = 6) and alloART (n = 9) of the entire anorectal segment and micro-anastomosis of the inferior mesenteric vessels. Two animals died due to surgical complications, and the others survived until the endpoint of the experiment. Five animals with alloART showed clinical signs of immunologic rejection 3 weeks after transplantation, and autopsy histology on postoperative day 30 revealed moderate to severe rejection in the allografts.<br><br>CONCLUSIONS: In this review, we observed that ART in rats is viable and may allow further physiologic and immunologic studies of this procedure, a potential treatment for severe incontinence and permanent colostomy.}, }
@article {pmid38748640, year = {2024}, author = {He, N and Chen, K and Yu, S and Cui, L and Vu, SH and Jung, S and Lee, MS and Li, S}, title = {Stachyose Exerts Anticolitis Efficacy by Re-balancing Treg/Th17 and Activating the Butyrate-Derived PPARγ Signaling Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {21}, pages = {12171-12183}, doi = {10.1021/acs.jafc.4c01387}, pmid = {38748640}, issn = {1520-5118}, mesh = {Animals ; Mice ; Bacteria/classification/isolation &amp; purification/genetics ; *Butyrates ; *Colitis, Ulcerative/immunology/therapy/microbiology/drug therapy ; Dextran Sulfate/adverse effects ; *Gastrointestinal Microbiome/drug effects ; *Mice, Inbred C57BL ; Oligosaccharides/administration &amp; dosage ; *PPAR gamma/drug effects/genetics/metabolism ; *Signal Transduction/drug effects ; *T-Lymphocytes, Regulatory/drug effects/immunology ; *Th17 Cells/drug effects/immunology ; }, abstract = {Ulcerative colitis (UC) is a complex chronic inflammatory disease closely associated with gut homeostasis dysfunction. The previous studies have shown that stachyose, a functional food additive, has the potential to enhance gut health and alleviate UC symptoms. However, the underlying mechanism of its effects remains unknown. In this study, our findings showed that dietary supplements of stachyose had a significant dose-dependent protective effect on colitis symptoms, regulation of gut microbiota, and restoration of the Treg/Th17 cell balance in dextran sulfate sodium (DSS) induced colitis mice. To further validate these findings, we conducted fecal microbiota transplantation (FMT) to treat DSS-induced colitis in mice. The results showed that microbiota from stachyose-treated mice exhibited a superior therapeutic effect against colitis and effectively regulated the Treg/Th17 cell balance in comparison to the control group. Moreover, both stachyose supplementation and FMT resulted in an increase in butyrate production and the activation of PPARγ. However, this effect was partially attenuated by PPARγ antagonist GW9662. These results suggested that stachyose alleviates UC symptoms by modulating gut microbiota and activating PPARγ. In conclusion, our work offers new insights into the benefical effects of stachyose on UC and its potential role in modulating gut microbiota.}, }
@article {pmid38748594, year = {2024}, author = {Liu, S and Luo, X and Zhou, L and Xie, RH and He, Y}, title = {Microbiota transplantation in restoring cesarean-related infant dysbiosis: a new frontier.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2351503}, pmid = {38748594}, issn = {1949-0984}, mesh = {Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; *Cesarean Section/adverse effects ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Vagina/microbiology ; }, abstract = {C-section is crucial in reducing maternal and neonatal mortality when medically indicated, but one of its side effects could be the disruption of vertical transmission of maternal-infant microbiota during delivery, potentially leading to gut dysbiosis and increased disease risks in C-section infants. To address such dysbiosis, it seems reasonable to supplement "what is missing" during C-section procedure. This idea has prompted several clinical trials, including proof-of-concept, investigating interventions like vaginal microbial seeding, oral administration of maternal vaginal microbes and even oral administration of maternal fecal materials. Hereby, we have summarized these trials to help understand the current state of these researches, highlighting the predominantly pilot nature of most of these studies and emphasizing the need for well-designed studies with larger sample to guide evidence-based medicine in the future.}, }
@article {pmid38746249, year = {2024}, author = {Ke, S and Villafuerte Gálvez, JA and Sun, Z and Cao, Y and Pollock, NR and Chen, X and Kelly, CP and Liu, YY}, title = {Rational Design of Live Biotherapeutic Products for the Prevention of Clostridioides difficile Infection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38746249}, issn = {2692-8205}, support = {K23 AI177749/AI/NIAID NIH HHS/United States ; R01 AI116596/AI/NIAID NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; }, abstract = {Clostridioides difficile infection (CDI) is one of the leading causes of healthcare- and antibiotic-associated diarrhea. While fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, its exact mechanisms of action and long-term safety are not fully understood. Defined consortia of clonal bacterial isolates, known as live biotherapeutic products (LBPs), have been proposed as an alternative therapeutic option. However, the rational design of LBPs remains challenging. Here, we employ a computational pipeline and three independent metagenomic datasets to systematically identify microbial strains that have the potential to inhibit CDI. We first constructed the CDI-related microbial genome catalog, comprising 3,741 non-redundant metagenome-assembled genomes (nrMAGs) at the strain level. We then identified multiple potential protective nrMAGs that can be candidates for the design of microbial consortia targeting CDI, including strains from Dorea formicigenerans, Oscillibacter welbionis, and Faecalibacterium prausnitzii. Importantly, some of these potential protective nrMAGs were found to play an important role in the success of FMT, and the majority of the top protective nrMAGs can be validated by various previously reported findings. Our results demonstrate a computational framework for the rational selection of microbial strains targeting CDI, paving the way for the computational design of microbial consortia against other enteric infections.}, }
@article {pmid38743445, year = {2024}, author = {Cafaro, G and Cruciani, G and Bruno, L and Dal Pozzolo, R and Colangelo, A and Tromby, F and Nicchi, M and Pianese, B and Perricone, C and Gerli, R and Bartoloni, E}, title = {Microbiota and arthritis: cause or consequence?.}, journal = {Clinical and experimental rheumatology}, volume = {42}, number = {5}, pages = {1097-1103}, doi = {10.55563/clinexprheumatol/f6q4dc}, pmid = {38743445}, issn = {0392-856X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Dysbiosis ; Animals ; Probiotics/therapeutic use ; Arthritis/microbiology ; Fecal Microbiota Transplantation ; Host-Pathogen Interactions ; Risk Factors ; }, abstract = {The relationship between intestinal microbiota and arthritis has garnered significant attention, with emerging evidence suggesting a potential association between dysbiosis and various forms of inflammatory arthropathies. While observational studies have provided valuable insights into microbiota alterations in patients with arthritis, establishing causality remains challenging. Observational data, influenced by multiple confounders such as environmental factors, medication effects, and dietary habits, are insufficient to conclusively determine whether microbiota changes are somehow causally linked to arthritis. The heterogeneity of results across independent studies further complicates interpretation. To further support this hypothesis, interventional randomised trials are deemed necessary, yet their implementation in this area presents significant technical limitations. Experimental animal models offer insights into potential pathogenic mechanisms linking dysbiosis to arthritis, including compromised intestinal barrier function, the role of microbiota-derived metabolites and molecular mimicry. However, conflicting findings underscore the complexity of hostmicrobiota interactions and the challenges in establishing causality.Efforts to modulate the microbiota for arthritis treatment or prevention have shown promise, yet efficacy and applicability remains uncertain. Antibacterial drugs, dietary interventions, probiotics, and faecal microbiota transplantation have been explored, but their clinical utility awaits further validation. In conclusion, while the association between intestinal microbiota and arthritis is increasingly recognised, establishing causality remains elusive.}, }
@article {pmid38743047, year = {2024}, author = {Namasivayam, S and Tilves, C and Ding, H and Wu, S and Domingue, JC and Ruiz-Bedoya, C and Shah, A and Bohrnsen, E and Schwarz, B and Bacorn, M and Chen, Q and Levy, S and Dominguez Bello, MG and Jain, SK and Sears, CL and Mueller, NT and Hourigan, SK}, title = {Fecal transplant from vaginally seeded infants decreases intraabdominal adiposity in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2353394}, pmid = {38743047}, issn = {1949-0984}, support = {K01 HL141589/HL/NHLBI NIH HHS/United States ; K12 HL143957/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Female ; Mice ; *Adiposity ; *Gastrointestinal Microbiome ; Male ; *Vagina/microbiology ; *Fecal Microbiota Transplantation ; *Feces/microbiology/chemistry ; Double-Blind Method ; Intra-Abdominal Fat/metabolism ; Infant ; Infant, Newborn ; }, abstract = {Exposing C-section infants to the maternal vaginal microbiome, coined "vaginal seeding", partially restores microbial colonization. However, whether vaginal seeding decreases metabolic disease risk is unknown. Therefore, we assessed the effect of vaginal seeding of human infants on adiposity in a murine model. Germ-free mice were colonized with transitional stool from human infants who received vaginal seeding or control (placebo) seeding in a double-blind randomized trial. There was a reduction in intraabdominal adipose tissue (IAAT) volume in male mice that received stool from vaginally seeded infants compared to control infants. Higher levels of isoleucine and lower levels of nucleic acid metabolites were observed in controls and correlated with increased IAAT. This suggests that early changes in the gut microbiome and metabolome caused by vaginal seeding have a positive impact on metabolic health.}, }
@article {pmid38739944, year = {2024}, author = {Zhu, M and Huang, Y and Wang, Z and Jin, Z and Cao, J and Zhong, Q and Xiong, Z}, title = {Fecal Microbiota Transplantation Attenuates Frailty via Gut-Muscle Axis in Old Mice.}, journal = {Aging and disease}, volume = {16}, number = {2}, pages = {1180-1198}, pmid = {38739944}, issn = {2152-5250}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Mice ; *Frailty/therapy/microbiology/metabolism ; Male ; *Aging/physiology ; Mice, Inbred C57BL ; *Muscle, Skeletal ; }, abstract = {Targeting adverse pathogenic gut microbiota regulation through fecal microbiota transplantation (FMT) may restore health and has been validated in some aging-related diseases. However, the mechanisms of the gut microbiota's role in frailty and whether modulation of the gut microbiota can treat age-related frailty remain largely unknown. To assess the effects of FMT on frailty, we used bidirectional fecal microbiota transplantation in young and old mice. We demonstrated that fecal bacteria transplanted from old mice into young mice reduced body weight and grip strength (p=0.002), and led to elevated inflammatory factors in young mice, but had no significant effect on intestinal barrier function. Notably, FMT treatment in older mice not only improved frailty (grip strength: p=0.036, low physical activity: p=0.020, running speed: p=0.048, running time: p=0.058, frailty score: p=0.027) and muscle mass, but also improved intestinal ecological imbalances, intestinal barrier function, and systemic inflammation (serum TNF-α: p=0.002, and IL-6: p<0.001). KEGG enrichment analysis of fecal metabolites showed that FMT may ameliorate frailty through the sphingolipid metabolism pathway. In addition, aged mice given FMT treatment showed a significant increase in the abundance of SCFA-producing bacteria and increased levels of short-chain fatty acids (butyric acid: p=0.084, propionic acid: p=0.028). Subsequent further verification found that FMT ameliorating frailty may be achieved through SCFAs metabolism. Another mechanism study found that FMT reduces lipopolysaccharide levels (p<0.001), thereby inhibiting the TLR4/NF-κB signaling pathway and its downstream pro-inflammatory products. Therefore, regulating SCFAs metabolism by altering gut microbial composition and targeting the gut-muscle axis with LPS/TLR4 pathways may be potential strategies to treat frailty in older adults.}, }
@article {pmid38739837, year = {2024}, author = {Herbin, SR and Crum, H and Gens, K}, title = {Breaking the Cycle of Recurrent Clostridioides difficile Infections: A Narrative Review Exploring Current and Novel Therapeutic Strategies.}, journal = {Journal of pharmacy practice}, volume = {37}, number = {6}, pages = {1361-1373}, doi = {10.1177/08971900241248883}, pmid = {38739837}, issn = {1531-1937}, mesh = {Humans ; *Clostridium Infections/drug therapy/therapy ; *Fecal Microbiota Transplantation/methods ; *Anti-Bacterial Agents/therapeutic use ; *Recurrence ; *Clostridioides difficile ; Gastrointestinal Microbiome/physiology ; Broadly Neutralizing Antibodies/therapeutic use ; Antibodies, Monoclonal ; }, abstract = {Clostridioides difficile is a toxin-producing bacteria that is a main cause of antibiotic-associated diarrhea. Clostridioides difficile infections (CDI) are associated with disruptions within the gastrointestinal (GI) microbiota which can be further exacerbated by CDI-targeted antibiotic treatment thereby causing recurrent CDI (rCDI) and compounding the burden placed on patients and the healthcare system. Treatment of rCDI consists of antibiotics which can be paired with preventative therapeutics, such as bezlotoxumab or fecal microbiota transplants (FMTs), if sustained clinical response is not obtained. Newer preventative strategies have been recently approved to assist in restoring balance within the GI system with the goal of preventing recurrent infections.}, }
@article {pmid38738157, year = {2024}, author = {Shimodaira, Y and Fukuda, S and Okubo, R and Onochi, K and Iijima, K}, title = {A Report of Ulcerative Colitis With Relapse on the Rectal Side of the Loop Sigmoid Colostomy and Not on the Oral Side.}, journal = {Cureus}, volume = {16}, number = {4}, pages = {e57941}, pmid = {38738157}, issn = {2168-8184}, abstract = {A patient who received a loop sigmoid colostomy was diagnosed with ulcerative colitis (pancolitis type) and treated with infliximab. Thereafter, he relapsed with intestinal inflammation only on the rectal side of the loop sigmoid colostomy and not on the oral side. Autologous fecal microbiota transplantation from the proximal intestine to the distal intestine was performed to treat the inflammation but was ineffective. He was treated with oral prednisolone and induced into remission. After analyzing fecal samples from the patient, we observed an alteration of the composition of the intestinal microbiota with intestinal inflammation, including a reduction of phylum Firmicutes in the inflamed distal intestine, whereas Firmicutes was conserved in the proximal non-inflamed intestine and recovered in the distal intestine after induction of remission. Thus, our results indicated that the inflammation was associated with an alteration of the intestinal microbiota.}, }
@article {pmid38737692, year = {2024}, author = {Sang, Y and Zheng, K and Zhao, Y and Liu, Y and Zhu, S and Xie, X and Shang, L and Liu, J and Li, L}, title = {Efficacy and regulatory strategies of gut microbiota in immunotherapy: a narrative review.}, journal = {Translational cancer research}, volume = {13}, number = {4}, pages = {2043-2063}, pmid = {38737692}, issn = {2219-6803}, abstract = {BACKGROUND AND OBJECTIVE: With advances in gut microbiome research, it has been recognized that the gut microbiome has an important and far-reaching impact on many human diseases, including cancer. Therefore, more and more researchers are focusing on the treatment of gut flora in tumors. In this article, we present a review of the mechanisms of gut microbes in tumor immunotherapy and related studies to provide reference for further research and insights into the clinical application of gut microbes.<br><br>METHODS: Between April 25, 2023, and November 25, 2023, we searched for articles published only in English between 1984 and 2023 using the databases PubMed, American Medical Association and Elsevier ScienceDirect using the keywords "gut microbiology" and "tumor" or "immunotherapy".<br><br>KEY CONTENT AND FINDINGS: The gastrointestinal tract contains the largest number of microorganisms in the human body. Microorganisms are involved in regulating many physiological activities of the body. Studies have shown that gut microbes and their derivatives are involved in the occurrence and development of a variety of inflammations and tumors, and changes in their abundance and proportion affect the degree of cancer progression and sensitivity to immunotherapy. Gut microbiota-based drug research is ongoing, and some anti-tumor studies have entered the clinical trial stage.<br><br>CONCLUSIONS: The abundance and proportion of intestinal microorganisms influence the susceptibility of tumors to tumor immunotherapy. This article reviewed the effects and mechanisms of gut microbes on tumor immunotherapy to further explore the medical value of gut microbes in tumor immunotherapy.}, }
@article {pmid38734322, year = {2024}, author = {Liu, X and Li, S and Wang, L and Ma, K}, title = {Microecological regulation in HCC therapy: Gut microbiome enhances ICI treatment.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1870}, number = {6}, pages = {167230}, doi = {10.1016/j.bbadis.2024.167230}, pmid = {38734322}, issn = {1879-260X}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Carcinoma, Hepatocellular/immunology/microbiology/therapy/drug therapy/pathology ; *Liver Neoplasms/immunology/drug therapy/microbiology/therapy/pathology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Immunotherapy/methods ; Animals ; }, abstract = {The exploration of the complex mechanisms of cancer immunotherapy is rapidly evolving worldwide, and our focus is on the interaction of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors (ICIs), particularly as it relates to the regulatory role of the gut microbiome. An important basis for the induction of immune responses in HCC is the presence of specific anti-tumor cells that can be activated and reinforced by ICIs, which is why the application of ICIs results in sustained tumor response rates in the majority of HCC patients. However, mechanisms of acquired resistance to immunotherapy in unresectable HCC result in no long-term benefit for some patients. The significant heterogeneity of inter-individual differences in the gut microbiome in response to treatment with ICIs makes it possible to target modulation of specific gut microbes to assist in augmenting checkpoint blockade therapies in HCC. This review focuses on the complex relationship between the gut microbiome, host immunity, and HCC, and emphasizes that manipulating the gut microbiome to improve response rates to cancer ICI therapy is a clinical strategy with unlimited potential.}, }
@article {pmid38734214, year = {2024}, author = {Quan, M and Zhang, X and Fang, Q and Lv, X and Wang, X and Zong, Z}, title = {Fighting against Clostridioides difficile infection: Current medications.}, journal = {International journal of antimicrobial agents}, volume = {64}, number = {1}, pages = {107198}, doi = {10.1016/j.ijantimicag.2024.107198}, pmid = {38734214}, issn = {1872-7913}, mesh = {Humans ; *Clostridium Infections/drug therapy/prevention &amp; control ; *Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/drug effects ; *Fecal Microbiota Transplantation ; Vancomycin/therapeutic use ; Fidaxomicin/therapeutic use ; }, abstract = {Clostridioides difficile (formerly Clostridium difficile) has been regarded as an 'urgent threat' and a significant global health problem, as life-threatening diarrhoea and refractory recurrence are common in patients with C. difficile infection (CDI). Unfortunately, the available anti-CDI drugs are limited. Recent guidelines recommend fidaxomicin and vancomycin as first-line drugs to treat CDI, bezlotoxumab to prevent recurrence, and faecal microbiota transplantation for rescue treatment. Currently, researchers are investigating therapeutic antibacterial drugs (e.g. teicoplanin, ridinilazole, ibezapolstat, surotomycin, cadazolid, and LFF571), preventive medications against recurrence (e.g. Rebyota, Vowst, VP20621, VE303, RBX7455, and MET-2), primary prevention strategies (e.g. vaccine, ribaxamase, and DAV132) and other anti-CDI medications in the preclinical stage (e.g. Raja 42, Myxopyronin B, and bacteriophage). This narrative review summarises current medications, including newly marketed drugs and products in development against CDI, to help clinicians treat CDI appropriately and to call for more research on innovation.}, }
@article {pmid38733907, year = {2024}, author = {Ruan, Y and Ren, G and Wang, M and Lv, W and Shimizu, K and Zhang, C}, title = {The dual role of 20(S)-protopanaxadiol in alleviating pulmonary fibrosis through the gut-lung axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {129}, number = {}, pages = {155699}, doi = {10.1016/j.phymed.2024.155699}, pmid = {38733907}, issn = {1618-095X}, mesh = {Animals ; *Sapogenins/pharmacology ; *Pulmonary Fibrosis/drug therapy ; *Gastrointestinal Microbiome/drug effects ; *Lung/drug effects ; Mice ; *Panax/chemistry ; *Disease Models, Animal ; *Mice, Inbred C57BL ; Bleomycin ; Fecal Microbiota Transplantation ; Male ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Pulmonary Fibrosis (PF) is a progressive lung disease characterized by the diffuse interstitial tissue, leading to severe breathing difficulties. The existing treatment methods are primarily aimed at slowing the progression of the disease, underscoring the urgent need to discover new drug interventions targeting novel sites. The "gut-lung axis" represents a complex bidirectional communication system where the gut microbiota not only influences lung immunity but also responds to lung-derived signals. Recent advances have uncovered that alterations in gut microbiota composition can significantly impact respiratory diseases, offering new insights into their pathogenesis and potential therapeutic approaches.<br><br>METHODS: This study is based on the fundamental concepts of the lung-gut axis and our previous research, further exploring the potential mechanisms of 20(S)-Protopanaxadiol (PPD) in ginseng against PF. We utilized a bleomycin-induced mouse model of PF and employed metabolomics and 16S rRNA sequencing to investigate the pathways through which PPD regulates the pulmonary fibrosis process via the gut-lung axis. Finally, we employed strategies such as antibiotic-induced microbiota disruption and fecal microbiota transplantation (FMT) to provide a comprehensive perspective on how PPD regulates pulmonary fibrosis through gut microbiota.<br><br>RESULTS: The results of the bleomycin (BLM) mouse model of PF proved that PPD can directly act on the glycolysis- related metabolic reprogramming process in lung and the AMPK/STING pathway to improve PF. Combined the analysis of gut microbiota and related metabolites, we found that PPD can regulate the process of PF through the gut-lung axis target points G6PD and SPHK1. FMT and antibiotic-induced microbiota disruption further confirmed intermediate effect of gut microbiota in PF process and the treatment of PPD. Our study suggests that PPD can alleviate the process of pulmonary fibrosis either by directly acting on the lungs or by regulating the gut microbiota.<br><br>CONCLUSION: This study positions PPD as a vanguard in the therapeutic landscape for pulmonary fibrosis, offering a dual mechanism of action that encompasses both modulation of gut microbiota and direct intervention at molecular targets. These insights highlight the immense therapeutic potential of harnessing the gut-lung axis.}, }
@article {pmid38733623, year = {2024}, author = {Ishikawa, D and Zhang, X and Nomura, K and Shibuya, T and Hojo, M and Yamashita, M and Koizumi, S and Yamazaki, F and Iwamoto, S and Saito, M and Kunigo, K and Nakano, R and Honma, N and Urakawa, I and Nagahara, A}, title = {Anti-inflammatory Effects of Bacteroidota Strains Derived From Outstanding Donors of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {30}, number = {11}, pages = {2136-2145}, doi = {10.1093/ibd/izae080}, pmid = {38733623}, issn = {1536-4844}, support = {JP22ae0121038//Japan Agency for Medical Research and Development/ ; }, mesh = {*Fecal Microbiota Transplantation ; *Colitis, Ulcerative/microbiology/therapy/immunology ; Animals ; Mice ; Humans ; *Feces/microbiology ; *Interleukin-10/metabolism ; Disease Models, Animal ; Male ; Bacteroidetes ; Female ; Gastrointestinal Microbiome ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Dextran Sulfate ; Anti-Inflammatory Agents ; }, abstract = {BACKGROUND: The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal microbiota transplantation therapy. We hypothesized that certain Bacteroidota may advance ulcerative colitis treatment. Accordingly, we aimed to evaluate the anti-inflammatory effects of Bacteroidota strains isolated from donors.<br><br>METHODS: Donors with proven efficacy of fecal microbiota transplantation for ulcerative colitis were selected, and Bacteroidota strains were isolated from their stools. The immune function of Bacteroidota isolates was evaluated through in vitro and in vivo studies.<br><br>RESULTS: Twenty-four Bacteroidota strains were isolated and identified. Using an in vitro interleukin (IL)-10 induction assay, we identified 4 Bacteroidota strains with remarkable IL-10-induction activity. Of these, an Alistipes putredinis strain exhibited anti-inflammatory effects in a mouse model of colitis induced by sodium dextran sulfate and oxazolone. However, 16S rRNA gene-based sequencing analysis of A. putredinis cultures in the in vivo study revealed unexpected Veillonella strain contamination. A second in vitro study confirmed that the coculture exhibited an even more potent IL-10-inducing activity. Furthermore, the production of A. putredinis-induced IL-10 was likely mediated via toll-like receptor 2 signaling.<br><br>CONCLUSIONS: This study demonstrated that A. putredinis, a representative Bacteroidota species, exhibits anti-inflammatory effects in vivo and in vitro; however, the effects of other Bacteroidota species remain unexplored. Our fecal microbiota transplantation-based reverse translation approach using promising bacterial species may represent a breakthrough in microbiome drug development for controlling dysbiosis during ulcerative colitis.}, }
@article {pmid38732527, year = {2024}, author = {Ouyang, Q and Li, X and Liang, Y and Liu, R}, title = {Sea Buckthorn Polysaccharide Ameliorates Colitis.}, journal = {Nutrients}, volume = {16}, number = {9}, pages = {}, pmid = {38732527}, issn = {2072-6643}, mesh = {Animals ; *Hippophae/chemistry ; *Polysaccharides/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Mice ; Colitis/drug therapy/chemically induced/microbiology ; Colitis, Ulcerative/microbiology/drug therapy ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Fecal Microbiota Transplantation ; Colon/drug effects/microbiology/metabolism ; Dextran Sulfate ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Fruit/chemistry ; Fatty Acids, Volatile/metabolism ; }, abstract = {Ulcerative colitis (UC) is characterized by chronic inflammation and ulceration of the intestinal inner lining, resulting in various symptoms. Sea buckthorn berries contain a bioactive compound known as sea buckthorn polysaccharide (SBP). However, the precise mechanisms underlying the impact of SBP on UC remain unclear. In this study, we investigated the effects of pretreatment with SBP on colitis induced by DSS. Our findings demonstrate that SBP pretreatment effectively reduces inflammation, oxidative stress, and intestinal barrier damage associated with colitis. To further elucidate the role of SBP-modulated gut microbiota in UC, we performed fecal microbiota transplantation (FMT) on DSS-treated mice. The microbiota from SBP-treated mice exhibits notable anti-inflammatory and antioxidant effects, improves colonic barrier integrity, and increases the abundance of beneficial bacteria, as well as enhancing SCFA production. Collectively, these results strongly indicate that SBP-mediated amelioration of colitis is attributed to its impact on the gut microbiota, particularly through the promotion of SCFA-producing bacteria and subsequent elevation of SCFA levels. This study provides compelling evidence supporting the efficacy of pre-emptive SBP supplementation in alleviating colitis symptoms by modulating the gut microbiota, thereby offering novel insights into the potential of SBP as a regulator of the gut microbiota for colitis relief.}, }
@article {pmid38732276, year = {2024}, author = {Boicean, A and Ichim, C and Todor, SB and Anderco, P and Popa, ML}, title = {The Importance of Microbiota and Fecal Microbiota Transplantation in Pancreatic Disorders.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {38732276}, issn = {2075-4418}, abstract = {The role of the intestinal microbiota in the diagnosis and treatment of pancreatic diseases is increasingly significant. Consequently, fecal microbiota transplantation (FMT) is emerging as a promising therapeutic avenue for various pancreatic disorders, including cancer, pancreatitis, and type 1 diabetes (T1D). This innovative procedure entails transferring gut microbiota from healthy donors to individuals affected by pancreatic ailments with the potential to restore intestinal balance and alleviate associated symptoms. FMT represents a pioneering approach to improve patient outcomes in pancreatic diseases, offering tailored treatments customized to individual microbiomes and specific conditions. Recent research highlights the therapeutic benefits of targeting the gut microbiota for personalized interventions in pancreatic disorders. However, a comprehensive understanding of the intricate interplay between gut microbiota and pancreatic physiology warrants further investigation. The necessity for additional studies and research endeavors remains crucial, especially in elucidating both adult and pediatric cases affected by pathological pancreatic conditions.}, }
@article {pmid38729481, year = {2024}, author = {Xia, T and He, W and Luo, Z and Wang, K and Tan, X}, title = {Achyranthes bidentata polysaccharide ameliorates type 2 diabetes mellitus by gut microbiota-derived short-chain fatty acids-induced activation of the GLP-1/GLP-1R/cAMP/PKA/CREB/INS pathway.}, journal = {International journal of biological macromolecules}, volume = {270}, number = {Pt 2}, pages = {132256}, doi = {10.1016/j.ijbiomac.2024.132256}, pmid = {38729481}, issn = {1879-0003}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Fatty Acids, Volatile/metabolism ; *Polysaccharides/pharmacology/chemistry ; Mice ; *Diabetes Mellitus, Type 2/drug therapy/metabolism ; *Glucagon-Like Peptide 1/metabolism ; *Cyclic AMP/metabolism ; *Cyclic AMP Response Element-Binding Protein/metabolism ; *Achyranthes/chemistry ; *Glucagon-Like Peptide-1 Receptor/metabolism ; *Cyclic AMP-Dependent Protein Kinases/metabolism ; Male ; Signal Transduction/drug effects ; Insulin/metabolism/blood ; Diabetes Mellitus, Experimental/drug therapy/metabolism ; }, abstract = {Gut microbiota variances reflecting the severity type 2 diabetes mellitus (T2DM). Achyranthes bidentata polysaccharide (ABP) can regulate gut microbiota. However, the hypoglycemic effect and underlying mechanism of ABP remain unclear. Herein, we characterized the structure of ABP and revealed the hypoglycemic effect of ABP in mice with T2DM. ABP repaired the intestinal barrier in T2DM mice and regulated the composition and abundance of gut microbiota, especially increasing bacteria which producing short-chain fatty acids (SCFAs), then increasing glucagon-like peptide-1 (GLP-1) level. The abundance of these bacteria was positively correlated with blood lipid and INS levels, negatively correlated with FBG levels. Colon transcriptome data and immunohistochemistry demonstrated that the alleviating T2DM effect of ABP was related to activation of the GLP-1/GLP-1 receptor (GLP-1R)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-response element binding protein (CREB)/INS pathway. Fecal microbiota transplantation (FMT) confirmed the transmissible efficacy of ABP through gut microbiota. Overall, our research shows that ABP plays a hypoglycemic role by increasing gut microbiota-derived SCFAs levels, and activating the GLP-1/GLP-1R/cAMP/PKA/CREB/INS pathway, emphasizing ABP as promising T2DM therapeutic candidates.}, }
@article {pmid38728472, year = {2024}, author = {Ugwu, OP and Alum, EU and Okon, MB and Obeagu, EI}, title = {Mechanisms of microbiota modulation: Implications for health, disease, and therapeutic interventions.}, journal = {Medicine}, volume = {103}, number = {19}, pages = {e38088}, pmid = {38728472}, issn = {1536-5964}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Anti-Bacterial Agents/therapeutic use ; Probiotics/therapeutic use ; Gastrointestinal Diseases/therapy/microbiology ; }, abstract = {Microbiota modulation, the intentional change in the structure and function of the microbial community, is an emerging trajectory that holds the promise to mitigate an infinite number of health issues. The present review illustrates the underlying principles of microbiota modulation and the various applications of this fundamental process to human health, healthcare management, and pharmacologic interventions. Different strategies, directing on dietary interventions, fecal microbiota transplantation, treatment with antibiotics, bacteriophages, microbiome engineering, and modulation of the immune system, are described in detail. This therapeutic implication is reflected in clinical applications to gastrointestinal disorders and immune-mediated diseases for microbiota-modulating agents. In addition to this, the review outlines the challenges of translating researched outcomes into clinical practice to consider safety and provides insights into future research directions of this rapidly developing area.}, }
@article {pmid38727248, year = {2024}, author = {Hao, QY and Yan, J and Wei, JT and Zeng, YH and Feng, LY and Que, DD and Li, SC and Guo, JB and Fan, Y and Ding, YF and Zhang, XL and Yang, PZ and Gao, JW and Li, ZH}, title = {Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2351532}, pmid = {38727248}, issn = {1949-0984}, mesh = {Animals ; Humans ; Male ; Rats ; Feces/microbiology ; *Gastrointestinal Microbiome ; Inflammasomes/metabolism ; *Lipopolysaccharides/metabolism ; Muscle, Smooth, Vascular/metabolism/pathology ; Myocytes, Smooth Muscle/metabolism ; *NF-kappa B/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Osteogenesis/drug effects ; *Prevotella/metabolism ; Rats, Sprague-Dawley ; Renal Insufficiency, Chronic/complications/microbiology/pathology ; *Signal Transduction ; Toll-Like Receptor 4/metabolism/genetics ; *Vascular Calcification/metabolism/microbiology/pathology ; }, abstract = {Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.}, }
@article {pmid38726585, year = {2024}, author = {Yakout, A and Bi, Y and Harris, DM}, title = {Clostridioides Difficile: A Concise Review of Best Practices and Updates.}, journal = {Journal of primary care &amp; community health}, volume = {15}, number = {}, pages = {21501319241249645}, pmid = {38726585}, issn = {2150-1327}, mesh = {Humans ; *Clostridium Infections/prevention &amp; control/diagnosis/therapy ; *Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; Cross Infection/prevention &amp; control ; Practice Guidelines as Topic ; Fidaxomicin/therapeutic use ; Metronidazole/therapeutic use ; }, abstract = {Clostridioides difficile infection (CDI) is one of the most common and severe nosocomial infections worldwide. It can also affect healthy individuals in the community. The incidence of CDI has been on the rise globally for the past decade, necessitating a proactive approach to combat its spread; new strategies are being developed to enhance diagnostic accuracy and optimize treatment outcomes. Implementing the 2-step testing has increased diagnostic specificity, reducing the usage of CD-specific antibiotics with no concomitant increase in surgical complication rates. In 2021, the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) shifted its preference for initial treatment to fidaxomicin over vancomycin and metronidazole due to its lower recurrence rate. It also prioritized fidaxomicin for the treatment of recurrent CDI. There are new developments on the frontiers of fecal microbiota therapies, with RBX2660 and SER-109 approved recently by the FDA for prevention, with other microbiome-based therapies in various development and clinical trials. This review offers providers an updated and practical guide for CDI management.}, }
@article {pmid38724904, year = {2024}, author = {Wang, L and Guo, G and Xu, Y and Li, L and Yang, B and Zhao, D and Tian, H and Ye, C and Lin, Z and Cui, J and Li, N and Huang, L and Chen, Q}, title = {The effect of fecal microbiota transplantation on antibiotic-associated diarrhea and its impact on gut microbiota.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {160}, pmid = {38724904}, issn = {1471-2180}, mesh = {Humans ; *Diarrhea/microbiology/therapy ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Female ; Male ; Middle Aged ; *Anti-Bacterial Agents/adverse effects ; *Feces/microbiology ; Adult ; *RNA, Ribosomal, 16S/genetics ; Aged ; Treatment Outcome ; Bacteria/classification/isolation &amp; purification/genetics ; }, abstract = {BACKGROUND: Antibiotic-associated diarrhea (AAD) refers to symptoms of diarrhea that cannot be explained by other causes after the use of antibiotics. AAD is thought to be caused by a disruption of intestinal ecology due to antibiotics. Fecal Microbiota Transplantation (FMT) is a treatment method that involves transferring microbial communities from the feces of healthy individuals into the patient's gut.<br><br>METHOD: We selected 23 AAD patients who received FMT treatment in our department. Before FMT, we documented patients' bowel movement frequency, abdominal symptoms, routine blood tests, and inflammatory markers, and collected fecal samples for 16S rRNA sequencing to observe changes in the intestinal microbiota. Patients' treatment outcomes were followed up 1 month and 3 months after FMT.<br><br>RESULTS: Out of the 23 AAD patients, 19 showed a clinical response to FMT with alleviation of abdominal symptoms. Among them, 82.61% (19/23) experienced relief from diarrhea, 65% (13/20) from abdominal pain, 77.78% (14/18) from abdominal distension, and 57.14% (4/7) from bloody stools within 1 month after FMT. Inflammatory markers IL-8 and CRP significantly decreased after FMT, but there were no noticeable changes in WBC, IL-6, and TNF-&#x3b1; before and after transplantation. After FMT, the abundance of Bacteroides and Faecalibacterium increased in patients' fecal samples, while the abundance of Escherichia-Shigella and Veillonella decreased.<br><br>CONCLUSION: FMT has a certain therapeutic effect on AAD, and can alleviate abdominal symptoms and change the intestinal microbiota of patients.}, }
@article {pmid38722758, year = {2024}, author = {Imamura, Y and Motooka, D and Nakajima, Y and Ito, S and Kitakaze, M and Iida, T and Nakamura, S}, title = {Turicibacter faecis sp. nov., isolated from faeces of heart failure mouse model.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {74}, number = {5}, pages = {}, pmid = {38722758}, issn = {1466-5034}, mesh = {Animals ; *RNA, Ribosomal, 16S/genetics ; *Feces/microbiology ; *Phylogeny ; Mice ; *Base Composition ; *DNA, Bacterial/genetics ; *Bacterial Typing Techniques ; *Sequence Analysis, DNA ; *Heart Failure/microbiology ; *Disease Models, Animal ; Genome, Bacterial ; Male ; Fatty Acids ; }, abstract = {Strain TC023[T], a Gram-positive, long, rod-shaped, spore-forming anaerobe, was isolated from the faeces of a heart failure mouse model. The strain formed greyish-white coloured colonies with a convex elevation on brain-heart infusion medium supplemented with 0.1 % sodium taurocholate, incubated at 37 °C for 2 days. Taxonomic analysis based on the 16S rRNA gene sequence showed that TC023[T] belonged to the genus Turicibacter, and was closely related to Turicibacter bilis MMM721[T] (97.6 %) and Turicibacter sanguinis MOL361[T] (97.4 %). The whole genome of the strain has a G+C content of 37.3 mol%. The average nucleotide identity and genome-to-genome distance between TC023[T] and Turicibacter bilis MMM721[T] were 77.6 % and 24.3 %, respectively, and those with Turicibacter sanguinis MOL361[T] were 75.4 % and 24.3 %, respectively. These genotypic, phenotypic, and biochemical analyses indicated that the isolate represents a novel species in the genus Turicibacter, and the name Turicibacter faecis sp. nov. is proposed. The type strain is TC023[T] (RIMD 2002001[T]=TSD 372[T]).}, }
@article {pmid38720654, year = {2024}, author = {Khalid, A and Huang, Z and Khan, IM and Khalid, F and Nassar, N and Jiang, X and Cheng, M and Zhan, K and Wang, Z}, title = {Improving broiler health through cecal microbiota transplantation: a comprehensive study on growth, immunity, and microbial diversity.}, journal = {Journal of animal science}, volume = {102}, number = {}, pages = {}, pmid = {38720654}, issn = {1525-3163}, mesh = {Animals ; *Chickens/growth &amp; development/microbiology ; *Cecum/microbiology ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Random Allocation ; Male ; Diet/veterinary ; }, abstract = {Cecal microbiota has emerged as a prominent intervention target for improving the production and welfare of poultry. This is essential for the overall health and performance of broiler chickens. The current study focused on investigating the effect of cecal microbiota transplantation (CMT) from healthy donor chickens on the growth performance, immunity, and microbial composition of newly hatched chicks and evaluated the effect of sample storage on the microbial diversity of the cecal samples. A healthy "Wannan Yellow Chicken line" was selected as the donor, and 180 1-d-old chicks from the same line were used as recipients for a 60-d feed trial. The chicks were randomly allocated to three groups (60 birds per group) with three replicates in each group. The three treatment groups were CMT-0 (control, normal saline solution), CMT-I (1:12 cecal content, normal saline supplemented with 10% glycerol), and CMT-II (1:6 cecal content, normal saline supplemented with 10% glycerol). The results of weight gain and absolute organ weight showed significant improvements in the CMT-II group compared with the CMT-0 group. Serum IgG level was significantly improved (P < 0.05) in CMT-I compared with that in the CMT-0. However, IL-6 levels increased in CMT-I and then significantly decreased in CMT-II. The cecal microbial diversity of CMT treatment was compared between two groups, fresh samples (FS) and stored samples at-80 °C (SS). The results showed that beneficial taxa, such as Firmicutes and Verrucomicrobiota, were substantially more abundant in both CMT-I and CMT-II than in CMT-0 in both FS and SS. Microbial function analysis at levels 1, 2, and 3 showed improved metabolism, genetic information processing, cellular processes, environmental information processing, and organismal systems in CMT-I and CMT-II for both FS and SS groups. However, the SS group showed decreased microbial diversity and function. To conclude, cecal microbiota transplantation is a promising strategy for enhancing the productivity and health of broiler chickens.}, }
@article {pmid38720628, year = {2024}, author = {Leibovitzh, H and Sarbagili Shabat, C and Hirsch, A and Zittan, E and Mentella, MC and Petito, V and Cohen, NA and Ron, Y and Fliss Isakov, N and Pfeffer, J and Yaakov, M and Fanali, C and Turchini, L and Masucci, L and Quaranta, G and Kolonimos, N and Godneva, A and Weinberger, A and Scaldaferri, F and Maharshak, N}, title = {Faecal Transplantation for Ulcerative Colitis From Diet Conditioned Donors Followed by Dietary Intervention Results in Favourable Gut Microbial Profile Compared to Faecal Transplantation Alone.}, journal = {Journal of Crohn's &amp; colitis}, volume = {18}, number = {10}, pages = {1606-1614}, doi = {10.1093/ecco-jcc/jjae062}, pmid = {38720628}, issn = {1876-4479}, support = {//Pinkerton Foundation/ ; //Azrieli Foundation/ ; }, mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology/diet therapy ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Male ; Female ; Adult ; Middle Aged ; *Feces/microbiology ; Colonoscopy/methods ; Diet/methods ; Enema/methods ; }, abstract = {BACKGROUND AND AIMS: Several faecal microbial transplantation [FMT] approaches for ulcerative colitis [UC] have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT UC Trial using FMT with the UC Exclusion Diet [UCED], compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and function.<br><br>METHODS: Subjects recruited to the CRAFT UC study with available pre- and post-intervention faecal samples were included. Donors received diet conditioning for 14 days based on the UCED principles. Group 1 received single FMT by colonoscopy [Day 1] and enemas [Days 2 and 14] without donors' dietary conditioning [N = 11]. Group 2 received FMT but with donors' dietary pre-conditioning and UCED for the patients [N&#x2005;=&#x2005;10]. Faecal samples were assessed by DNA shotgun metagenomic sequencing.<br><br>RESULTS: Following diet conditioning, donors showed depletion in metabolic pathways involved in biosynthesis of sulphur-containing amino acids. Only Group 2 showed significant shifts towards the donors' microbial composition [ADONIS: R2&#x2005;=&#x2005;0.15, p&#x2005;=&#x2005;0.008] and significantly increased Eubacterium_sp_AF228LB post-intervention [&#x3b2;-coefficient 2.66, 95% confidence interval 2.1-3.3, q&#x2005;<&#x2005;0.05] which was inversely correlated with faecal calprotectin [rho&#x2005;=&#x2005;-0.52, p&#x2005;=&#x2005;0.035]. Moreover, pathways involved in gut inflammation and barrier function including branched chain amino acids were enriched post-intervention in Group 2 and were significantly inversely correlated with faecal calprotectin.<br><br>CONCLUSION: FMT from diet conditioned donors followed by the UCED led to microbial alterations associated with favourable microbial profiles which correlated with decreased faecal calprotectin. Our findings support further exploration of the additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of UC.}, }
@article {pmid38720499, year = {2023}, author = {Ramakrishna, BS and Patankar, R}, title = {Antibiotic-associated Gut Dysbiosis.}, journal = {The Journal of the Association of Physicians of India}, volume = {71}, number = {11}, pages = {62-68}, doi = {10.59556/japi.71.0381}, pmid = {38720499}, issn = {0004-5772}, mesh = {*Dysbiosis/chemically induced ; Humans ; *Anti-Bacterial Agents/adverse effects ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Phage Therapy/methods ; }, abstract = {The human gut microbiota plays a crucial role in maintaining overall health. However, the widespread use of antibiotics has raised concerns about its impact on the microbial ecosystem. This review explores the multifaceted relationship between antibiotics and gut dysbiosis, highlighting the mechanisms underlying these interactions and their implications for human health. Antibiotics, while invaluable in treating infections, disrupt the gut microbiota by indiscriminately targeting both harmful and beneficial microorganisms. This disturbance leads to a reduction in microbial diversity, altered metabolite production, and compromised immune responses, resulting in a state referred to as dysbiosis. Broad-spectrum antibiotics tend to induce more severe dysbiosis compared to narrow-spectrum agents. Antibiotic-induced dysbiosis has been linked to the onset and progression of these disorders, emphasizing the far-reaching consequences of microbial imbalance. The review highlights various strategies to mitigate the adverse effects of antibiotics on gut health, like probiotics, fecal microbiota transplantation (FMT), and phage therapy, as promising approaches to restore and maintain a balanced gut microbiota. How to cite this article: Ramakrishna BS, Patankar R. Antibiotic-associated Gut Dysbiosis. J Assoc Physicians India 2023;71(11):62-68.}, }
@article {pmid38720361, year = {2024}, author = {Huang, C and Li, X and Li, H and Chen, R and Li, Z and Li, D and Xu, X and Zhang, G and Qin, L and Li, B and Chu, XM}, title = {Role of gut microbiota in doxorubicin-induced cardiotoxicity: from pathogenesis to related interventions.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {433}, pmid = {38720361}, issn = {1479-5876}, support = {82172574//National Natural Science Foundation of China/ ; 81871231//National Natural Science Foundation of China/ ; ZR2020MH016//Natural Science Foundation of Shandong Province/ ; ZR202209280042//Natural Science Foundation of Shandong Province/ ; YJKT202171//Project of Shandong Province Higher Educational Science and Technology Program/ ; tsqn202103056//Taishan Scholar Foundation of Shandong Province/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Doxorubicin/adverse effects ; *Cardiotoxicity/etiology ; Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; }, abstract = {Doxorubicin (DOX) is a broad-spectrum and highly efficient anticancer agent, but its clinical implication is limited by lethal cardiotoxicity. Growing evidences have shown that alterations in intestinal microbial composition and function, namely dysbiosis, are closely linked to the progression of DOX-induced cardiotoxicity (DIC) through regulating the gut-microbiota-heart (GMH) axis. The role of gut microbiota and its metabolites in DIC, however, is largely unelucidated. Our review will focus on the potential mechanism between gut microbiota dysbiosis and DIC, so as to provide novel insights into the pathophysiology of DIC. Furthermore, we summarize the underlying interventions of microbial-targeted therapeutics in DIC, encompassing dietary interventions, fecal microbiota transplantation (FMT), probiotics, antibiotics, and natural phytochemicals. Given the emergence of microbial investigation in DIC, finally we aim to point out a novel direction for future research and clinical intervention of DIC, which may be helpful for the DIC patients.}, }
@article {pmid38719790, year = {2024}, author = {Grodin, EN and Burnette, EM and Rodriguez, C and Fulcher, JA and Ray, LA}, title = {The gut microbiome in alcohol use disorder and alcohol-associated liver disease: A systematic review of clinical studies.}, journal = {Alcohol, clinical &amp; experimental research}, volume = {48}, number = {7}, pages = {1221-1242}, pmid = {38719790}, issn = {2993-7175}, support = {F31 AA028976/AA/NIAAA NIH HHS/United States ; T32 DA024635/DA/NIDA NIH HHS/United States ; 2019086/DDCF/Doris Duke Charitable Foundation/United States ; K24 AA025704/AA/NIAAA NIH HHS/United States ; K01 AA029712/AA/NIAAA NIH HHS/United States ; K08 AI124979/AI/NIAID NIH HHS/United States ; }, abstract = {Evidence suggests that a relationship exists between the gut microbiome and the pathogenesis of alcohol use disorder (AUD) and alcohol-associated liver disease (AALD). This systematic review identified studies that investigated the gut microbiome in individuals with an AUD or an AALD. A search was conducted on October 27, 2022, in PubMed, Web of Science, and Embase databases. Fifty studies satisfied eligibility criteria. Most studies found evidence for gut dysbiosis in individuals with AUD and AALD. Microbiome intervention studies have mostly been conducted in AALD patients; fecal microbial transplant interventions show the most promise. Because most studies were conducted cross-sectionally, the causal relationship between the gut microbiome and alcohol use is unknown. Furthermore, almost all studies have been conducted in predominantly male populations, leaving critical questions regarding sex differences and generalizability of the findings. The study summaries and recommendations provided in this review seek to identify areas for further research and to highlight potential gut microbial interventions for treating AUD and AALD.}, }
@article {pmid38718729, year = {2024}, author = {Gu, T and Kong, M and Duan, M and Chen, L and Tian, Y and Xu, W and Zeng, T and Lu, L}, title = {Cu exposure induces liver inflammation via regulating gut microbiota/LPS/liver TLR4 signaling axis.}, journal = {Ecotoxicology and environmental safety}, volume = {278}, number = {}, pages = {116430}, doi = {10.1016/j.ecoenv.2024.116430}, pmid = {38718729}, issn = {1090-2414}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Toll-Like Receptor 4/metabolism ; *Ducks ; *Signal Transduction/drug effects ; *Liver/drug effects ; *Lipopolysaccharides/toxicity ; *Copper/toxicity ; Cytokines/metabolism ; Inflammation/chemically induced/pathology ; Chemical and Drug Induced Liver Injury/pathology ; }, abstract = {Copper (Cu) serves as an essential cofactor in all organisms, yet excessive Cu exposure is widely recognized for its role in inducing liver inflammation. However, the precise mechanism by which Cu triggers liver inflammation in ducks, particularly in relation to the interplay in gut microbiota regulation, has remained elusive. In this investigation, we sought to elucidate the impact of Cu exposure on liver inflammation through gut-liver axis in ducks. Our findings revealed that Cu exposure markedly elevated liver AST and ALT levels and induced liver inflammation through upregulating pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and triggering the LPS/TLR4/NF-κB signaling pathway. Simultaneously, Cu exposure induced alterations in the composition of intestinal flora communities, notably increasing the relative abundance of Sphingobacterium, Campylobacter, Acinetobacter and reducing the relative abundance of Lactobacillus. Cu exposure significantly decreased the protein expression related to intestinal barrier (Occludin, Claudin-1 and ZO-1) and promoted the secretion of intestinal pro-inflammatory cytokines. Furthermore, correlation analysis was observed that intestinal microbiome and gut barrier induced by Cu were closely related to liver inflammation. Fecal microbiota transplantation (FMT) experiments further demonstrated the microbiota-depleted ducks transplanting fecal samples from Cu-exposed ducks disturbed the intestinal dysfunction, which lead to impaire liver function and activate the liver inflammation. Our study provided insights into the mechanism by which Cu exposure induced liver inflammation in ducks through the regulation of gut-liver axis. These results enhanced our comprehension of the potential mechanisms driving Cu-induced hepatotoxicity in avian species.}, }
@article {pmid38717124, year = {2024}, author = {Yadegar, A and Bar-Yoseph, H and Monaghan, TM and Pakpour, S and Severino, A and Kuijper, EJ and Smits, WK and Terveer, EM and Neupane, S and Nabavi-Rad, A and Sadeghi, J and Cammarota, G and Ianiro, G and Nap-Hill, E and Leung, D and Wong, K and Kao, D}, title = {Fecal microbiota transplantation: current challenges and future landscapes.}, journal = {Clinical microbiology reviews}, volume = {37}, number = {2}, pages = {e0006022}, pmid = {38717124}, issn = {1098-6618}, support = {PJT168954//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; //NIHR | NIHR Nottingham Biomedical Research Centre (BRC)/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; Clostridium Infections/therapy/microbiology ; Inflammatory Bowel Diseases/therapy/microbiology ; Animals ; }, abstract = {SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest in developing innovative therapeutic strategies for restoring gut microbiota. One such approach, fecal microbiota transplantation (FMT), is the main "whole gut microbiome replacement" strategy and has been integrated into clinical practice guidelines for treating recurrent Clostridioides difficile infection (rCDI). Furthermore, the potential application of FMT in other indications such as inflammatory bowel disease (IBD), metabolic syndrome, and solid tumor malignancies is an area of intense interest and active research. However, the complex and variable nature of FMT makes it challenging to address its precise functionality and to assess clinical efficacy and safety in different disease contexts. In this review, we outline clinical applications, efficacy, durability, and safety of FMT and provide a comprehensive assessment of its procedural and administration aspects. The clinical applications of FMT in children and cancer immunotherapy are also described. We focus on data from human studies in IBD in contrast with rCDI to delineate the putative mechanisms of this treatment in IBD as a model, including colonization resistance and functional restoration through bacterial engraftment, modulating effects of virome/phageome, gut metabolome and host interactions, and immunoregulatory actions of FMT. Furthermore, we comprehensively review omics technologies, metagenomic approaches, and bioinformatics pipelines to characterize complex microbial communities and discuss their limitations. FMT regulatory challenges, ethical considerations, and pharmacomicrobiomics are also highlighted to shed light on future development of tailored microbiome-based therapeutics.}, }
@article {pmid38716216, year = {2024}, author = {Tetali, B and Suresh, S}, title = {Management of irritable bowel syndrome: a narrative review.}, journal = {Translational gastroenterology and hepatology}, volume = {9}, number = {}, pages = {26}, pmid = {38716216}, issn = {2415-1289}, abstract = {BACKGROUND AND OBJECTIVE: As our understanding of the pathophysiology of irritable bowel syndrome (IBS) has advanced, so too has the therapeutic landscape, offering a myriad of approaches to alleviate symptoms and enhance the well-being of patients. This review paper is dedicated to a comprehensive exploration of the diverse therapeutic modalities available for managing IBS. By delving into the complexities of IBS therapeutics, our aim is to contribute to the enhancement of patient care and the overall quality of life for patients grappling with this complex condition.<br><br>METHODS: This review utilized information from PubMed/MEDLINE using the key search term "irritable bowel syndrome" as well as the 2020 American College of Gastroenterology (ACG) and 2022 American Gastroenterological Association (AGA) society guidelines on IBS. The search was restricted to articles in the English language only and included peer-reviewed observational studies and randomized controlled trials (RCTs) in adult patients from April 22, 2020 to October 16, 2023.<br><br>KEY CONTENT AND FINDINGS: This review will start with an overview of the current guidelines for pharmacologic therapies for IBS as recommended by the ACG and the AGA, with an emphasis on clinical trials published after the most recent guidelines. It will then delve into the literature on dietary modifications, probiotics, fecal microbiota transplant, behavioral therapy, and complementary and alternative medicine approaches to IBS.<br><br>CONCLUSIONS: It is evident that the management of IBS has transcended a one-size-fits-all approach. As the field of IBS management continues to evolve, it is imperative for physicians to stay informed and receptive to the array of therapeutic options available, ultimately providing patients with the most effective and personalized care.}, }
@article {pmid38715916, year = {2024}, author = {Hazan, S and Haroon, J and Jordan, S and Walker, SJ}, title = {Improvements in Gut Microbiome Composition and Clinical Symptoms Following Familial Fecal Microbiota Transplantation in a Nineteen-Year-Old Adolescent With Severe Autism.}, journal = {Journal of medical cases}, volume = {15}, number = {4-5}, pages = {82-91}, pmid = {38715916}, issn = {1923-4163}, abstract = {This case report describes a novel therapy for patients with severe autism spectrum disorder (ASD) that is worth further investigation. A 19-year-old male adolescent with ASD, who was not responding to standard treatment received fecal microbiota transplant (FMT) using donor material from his typically developing female sibling. The patient's ASD symptoms were assessed by assessors who were blind to the patient's past ASD symptomatology. Assessors used the Childhood Autism Rating Scale (CARS), an observation-based rating scale to assess developmental delay in children with autism (range of CARS scores is 15 - 60; a score > 28 is indicative of autism; higher score is positively correlated with degree of severity), at baseline and again at six timepoints post-FMT. The patient experienced marked improvements in microbiome diversity and composition over the year and a half period that followed the FMT procedure. Additionally, the patient who was previously nonverbal said his first two words and experienced a reduction in aggression 1-month post-FMT. To the authors' knowledge, this is the first report to demonstrate the use of familial FMT in an adolescent patient with ASD. Given that ASD symptom improvements post-FMT tend to occur in younger patients, the authors hypothesize that the use of a familial donor may be an important factor that contributed to the improved outcomes experienced by this older child.}, }
@article {pmid38713722, year = {2024}, author = {Yang, M and Zheng, X and Fan, J and Cheng, W and Yan, TM and Lai, Y and Zhang, N and Lu, Y and Qi, J and Huo, Z and Xu, Z and Huang, J and Jiao, Y and Liu, B and Pang, R and Zhong, X and Huang, S and Luo, GZ and Lee, G and Jobin, C and Eren, AM and Chang, EB and Wei, H and Pan, T and Wang, X}, title = {Antibiotic-Induced Gut Microbiota Dysbiosis Modulates Host Transcriptome and m[6]A Epitranscriptome via Bile Acid Metabolism.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {28}, pages = {e2307981}, pmid = {38713722}, issn = {2198-3844}, support = {K22CA234399/NH/NIH HHS/United States ; 32070615//National Natural Science Foundation of China/ ; 2021A1515010823//Guangdong Provincial Natural Science Foundation/ ; 81902093//National Natural Science Foundation of China/ ; 2024A04J6265//Guangzhou Science and Technology Project/ ; 2022A1515010569//Guangdong Provincial Natural Science Foundation/ ; P30 DK042086/DK/NIDDK NIH HHS/United States ; K22 CA234399/CA/NCI NIH HHS/United States ; P30 DK020595/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/genetics ; *Bile Acids and Salts/metabolism ; *Dysbiosis/metabolism/microbiology/genetics ; Mice ; *Transcriptome/genetics ; *Anti-Bacterial Agents/pharmacology ; *Adenosine/analogs &amp; derivatives/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Male ; }, abstract = {Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N[6]-methyladenosine (m[6]A), the most abundant mammalian mRNA modification. However, which and how gut microbiota-derived metabolites reprogram host transcriptome and m[6]A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota-derived metabolites impact host transcriptome and m[6]A epitranscriptome using multiple mouse models and multi-omics approaches. Various antibiotics-induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ-free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid-producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m[6]A epitranscriptome in multiple tissues. Mechanistically, the expression of m[6]A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m[6]A biology. Collectively, these results demonstrate that antibiotic-induced gut dysbiosis regulates the landscape of host transcriptome and m[6]A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.}, }
@article {pmid38712927, year = {2024}, author = {Zhang, S and Swarte, JC and Gacesa, R and Knobbe, TJ and Kremer, D and Jansen, BH and de Borst, MH and ,  and Harmsen, HJM and Erasmus, ME and Verschuuren, EAM and Bakker, SJL and Gan, CT and Weersma, RK and Björk, JR}, title = {The gut microbiome in end-stage lung disease and lung transplantation.}, journal = {mSystems}, volume = {9}, number = {6}, pages = {e0131223}, pmid = {38712927}, issn = {2379-5077}, mesh = {Humans ; *Lung Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Female ; Male ; Middle Aged ; Adult ; *Dysbiosis/microbiology ; Lung Diseases/microbiology/surgery ; Immunosuppressive Agents/therapeutic use/adverse effects ; Feces/microbiology ; Aged ; }, abstract = {Gut dysbiosis has been associated with impaired outcomes in liver and kidney transplant recipients, but the gut microbiome of lung transplant recipients has not been extensively explored. We assessed the gut microbiome in 64 fecal samples from end-stage lung disease patients before transplantation and 219 samples from lung transplant recipients after transplantation using metagenomic sequencing. To identify dysbiotic microbial signatures, we analyzed 243 fecal samples from age-, sex-, and BMI-matched healthy controls. By unsupervised clustering, we identified five groups of lung transplant recipients using different combinations of immunosuppressants and antibiotics and analyzed them in relation to the gut microbiome. Finally, we investigated the gut microbiome of lung transplant recipients in different chronic lung allograft dysfunction (CLAD) stages and longitudinal gut microbiome changes after transplantation. We found 108 species (58.1%) in end-stage lung disease patients and 139 species (74.7%) in lung transplant recipients that were differentially abundant compared with healthy controls, with several species exhibiting sharp longitudinal increases from before to after transplantation. Different combinations of immunosuppressants and antibiotics were associated with specific gut microbial signatures. We found that the gut microbiome of lung transplant recipients in CLAD stage 0 was more similar to healthy controls compared to those in CLAD stage 1. Finally, the gut microbial diversity of lung transplant recipients remained lower than the average gut microbial diversity of healthy controls up to more than 20 years post-transplantation. Gut dysbiosis, already present before lung transplantation was exacerbated following lung transplantation.IMPORTANCEThis study provides extensive insights into the gut microbiome of end-stage lung disease patients and lung transplant recipients, which warrants further investigation before the gut microbiome can be used for microbiome-targeted interventions that could improve the outcome of lung transplantation.}, }
@article {pmid38711648, year = {2024}, author = {Yi, C and Chen, J and She, X}, title = {The emerging role of the gut virome in necrotizing enterocolitis.}, journal = {Heliyon}, volume = {10}, number = {9}, pages = {e30496}, pmid = {38711648}, issn = {2405-8440}, abstract = {Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates, particularly preterm infants. Many factors can lead to NEC, but microbial dysbiosis is one of the most important risk factors that can induce this disease. Given the major role of the gut virome in shaping bacterial homeostasis, virome research is a fledgling but rapidly evolving area in the field of microbiome that is increasingly connected to human diseases, including NEC. This review provides an overview of the development of the gut virome in newborns, discusses its emerging role in NEC, and explores promising therapeutic applications, including phage therapy and fecal virome transplantation.}, }
@article {pmid38711536, year = {2024}, author = {Tuniyazi, M and Tang, R and Hu, X and Fu, Y and Zhang, N}, title = {Carbonate buffer mixture and fecal microbiota transplantation hold promising therapeutic effects on oligofructose-induced diarrhea in horses.}, journal = {Frontiers in veterinary science}, volume = {11}, number = {}, pages = {1388227}, pmid = {38711536}, issn = {2297-1769}, abstract = {Diarrhea is a common gastrointestinal disorder in horses, with diet-induced diarrhea being an emerging challenge. This study aimed to investigate the gut microbiota differences in healthy and diet-induced diarrheic horses and evaluate the effectiveness of fecal microbiota transplantation (FMT) and carbonate buffer mixture (CBM) as potential therapeutic approaches. Twenty healthy horses were included in the study, with four groups: Control, Diarrhea, CBM, and FMT. Diarrhea was induced using oligofructose, and fecal samples were collected for microbiota analysis. FMT and CBM treatments were administered orally using donor fecal matter, and formula mixture, respectively. Clinical parameters, serum levels, intestinal tissue histopathology, and fecal microbiota profiles were evaluated. The results showed that diarrhea induction disbalanced the gut microbiota with decreased diversity and richness, affected clinical parameters including elevated body temperature and diarrhea score, and decreased fecal pH, increased inflammatory responses such as increased serum LPS, IL-17A, lactic acid and total protein, and caused damage in the colon tissue. CBM and FMT treatments altered the gut microbiota composition, restoring it towards a healthier profile compared to diarrheic, restored the gut microbiota composition to healthier states, improved clinical symptoms including decreased body temperature and diarrhea score, and increased fecal pH, decreased inflammatory responses such as increased serum LPS, IL-17A, lactic acid and total protein, and repaired tissue damage. CBM and FMT Spearman correlation analysis identified specific bacterial taxa associated with host parameters and inflammation. FMT and CBM treatments showed promising therapeutic effects in managing oligofructose-induced diarrhea in horses. The findings provide valuable insights into the management and treatment of diarrhea in horses and suggest the potential of combined CBM and FMT approaches for optimal therapeutic outcomes.}, }
@article {pmid38709933, year = {2024}, author = {Chen, J and Liu, X and Zou, Y and Gong, J and Ge, Z and Lin, X and Zhang, W and Huang, H and Zhao, J and Saw, PE and Lu, Y and Hu, H and Song, E}, title = {A high-fat diet promotes cancer progression by inducing gut microbiota-mediated leucine production and PMN-MDSC differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {20}, pages = {e2306776121}, pmid = {38709933}, issn = {1091-6490}, support = {2019BT02Y198//Program for Guangdong Introducing Innovative and Enterpreneurial Teams/ ; 82330056//Natural Science Foundation of China/ ; 81730077//National Natural Science Foundation of China/ ; 92159303//National Natural Science Foundation of China/ ; 81930081//National Natural Science Foundation of China/ ; 82025026//National Natural Science Foundation of China/ ; 2022A1515110069//GDSTC | Basic and Applied Basic Research Foundation of Guangdong Province ()/ ; 2023B1212060013//Guangdong Science and Technology Department/ ; 20212200003//Bureau of Science and Technology of Guangzhou/ ; E2018096//Guang Dong Cheung Kong philanthropy Foundation/ ; }, mesh = {*Gastrointestinal Microbiome ; Animals ; *Diet, High-Fat/adverse effects ; *Leucine/metabolism ; Female ; Humans ; Mice ; *Myeloid-Derived Suppressor Cells/metabolism ; *Breast Neoplasms/pathology/microbiology/metabolism ; *Cell Differentiation ; *Disease Progression ; Obesity/microbiology/metabolism/pathology ; Cell Line, Tumor ; }, abstract = {A high-fat diet (HFD) is a high-risk factor for the malignant progression of cancers through the disruption of the intestinal microbiota. However, the role of the HFD-related gut microbiota in cancer development remains unclear. This study found that obesity and obesity-related gut microbiota were associated with poor prognosis and advanced clinicopathological status in female patients with breast cancer. To investigate the impact of HFD-associated gut microbiota on cancer progression, we established various models, including HFD feeding, fecal microbiota transplantation, antibiotic feeding, and bacterial gavage, in tumor-bearing mice. HFD-related microbiota promotes cancer progression by generating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, the HFD microbiota released abundant leucine, which activated the mTORC1 signaling pathway in myeloid progenitors for PMN-MDSC differentiation. Clinically, the elevated leucine level in the peripheral blood induced by the HFD microbiota was correlated with abundant tumoral PMN-MDSC infiltration and poor clinical outcomes in female patients with breast cancer. These findings revealed that the "gut-bone marrow-tumor" axis is involved in HFD-mediated cancer progression and opens a broad avenue for anticancer therapeutic strategies by targeting the aberrant metabolism of the gut microbiota.}, }
@article {pmid38708959, year = {2024}, author = {Kousgaard, SJ and Cold, F and Halkjær, SI and Petersen, AM and Kjeldsen, J and Hansen, JM and Dall, SM and Albertsen, M and Nielsen, HL and Kirk, KF and Duch, K and Sønderkær, M and Thorlacius-Ussing, O}, title = {The Effect of Non-pooled Multidonor Faecal Microbiota Transplantation for Inducing Clinical Remission in Patients with Chronic Pouchitis: Results from a Multicentre, Randomised, Double-blinded, Placebo-controlled Trial [MicroPouch].}, journal = {Journal of Crohn's &amp; colitis}, volume = {18}, number = {11}, pages = {1753-1766}, doi = {10.1093/ecco-jcc/jjae066}, pmid = {38708959}, issn = {1876-4479}, support = {20-10-0021//Aase og Ejnar Danielsens Fond/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Double-Blind Method ; Male ; *Pouchitis/therapy/microbiology ; Female ; Adult ; Chronic Disease ; Middle Aged ; *Remission Induction/methods ; Feces/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: To investigate if treatment with non-pooled, multidonor faecal microbiota transplantation [FMT] for 4 weeks was superior to placebo to induce clinical remission in patients with chronic pouchitis.<br><br>METHODS: The study was a randomised, double-blinded, placebo-controlled study with a 4-week intervention period and 12-month follow-up. Eligible patients with chronic pouchitis were recruited from five Danish hospitals. Participants were randomised to non-pooled, multidonor FMT derived from four faecal donors, or placebo. Treatment was delivered daily by enema for 2 weeks, followed by every second day for 2 weeks. Disease severity was accessed at inclusion and 30-day follow-up, using the Pouchitis Disease Activity Index [PDAI]; PDAI&#x2005;<7 was considered equivalent to clinical remission. Faecal samples from participants and donors were analysed by shotgun metagenomic sequencing.<br><br>RESULTS: Inclusion was stopped after inclusion of 30 participants who were randomised 1:1 for treatment with FMT or placebo. There was no difference in participants achieving clinical remission between the two groups at 30-day follow-up, relative risk 1.0 (95% CI [0.55; 1.81]). Treatment with FMT resulted in a clinically relevant increase in adverse events compared with placebo, incidence rate ratio 1.67 (95% CI [1.10; 2.52]); no serious adverse events within either group. Faecal microbiota transplantation statistically significantly increased the similarity of participant faecal microbiome to the faecal donor microbiome at 30-day follow-up [p&#x2005;=&#x2005;0.01], which was not seen after placebo.<br><br>CONCLUSIONS: Non-pooled, multidonor FMT was comparable to placebo in inducing clinical remission in patients with chronic pouchitis, but showed a clinically relevant increase in adverse events compared with placebo. ClincialTrials.gov number, NCT04100291.}, }
@article {pmid38708416, year = {2024}, author = {Zoghi, S and Sadeghpour Heravi, F and Nikniaz, Z and Shirmohamadi, M and Moaddab, SY and Ebrahimzadeh Leylabadlo, H}, title = {Gut microbiota and childhood malnutrition: Understanding the link and exploring therapeutic interventions.}, journal = {Engineering in life sciences}, volume = {24}, number = {5}, pages = {2300070}, pmid = {38708416}, issn = {1618-0240}, abstract = {Childhood malnutrition is a metabolic condition that affects the physical and mental well-being of children and leads to resultant disorders in maturity. The development of childhood malnutrition is influenced by a number of physiological and environmental factors including metabolic stress, infections, diet, genetic variables, and gut microbiota. The imbalanced gut microbiota is one of the main environmental risk factors that significantly influence host physiology and childhood malnutrition progression. In this review, we have evaluated the gut microbiota association with undernutrition and overnutrition in children, and then the quantitative and qualitative significance of gut dysbiosis in order to reveal the impact of gut microbiota modification using probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and engineering biology methods as new therapeutic challenges in the management of disturbed energy homeostasis. Understanding the host-microbiota interaction and the remote regulation of other organs and pathways by gut microbiota can improve the effectiveness of new therapeutic approaches and mitigate the negative consequences of childhood malnutrition.}, }
@article {pmid38707810, year = {2024}, author = {León-Janampa, N and Boennec, N and Le Tilly, O and Ereh, S and Herbet, G and Moreau, A and Gatault, P and Longuet, H and Barbet, C and Büchler, M and Baron, C and Gaudy-Graffin, C and Brand, D and Marlet, J}, title = {Relevance of Tacrolimus Trough Concentration and Hepatitis E virus Genetic Changes in Kidney Transplant Recipients With Chronic Hepatitis E.}, journal = {Kidney international reports}, volume = {9}, number = {5}, pages = {1333-1342}, pmid = {38707810}, issn = {2468-0249}, abstract = {INTRODUCTION: Hepatitis E virus (HEV) can cause chronic infection (≥3 months) and cirrhosis in immunocompromised patients, especially kidney transplant recipients. Low alanine aminotransferase (ALT) levels and high HEV intrahost diversity have previously been associated with evolution toward chronicity in these patients. We hypothesized that additional clinical and viral factors could be associated with the risk of chronic HEV infection.<br><br>METHODS: We investigated a series of 27 kidney transplant recipients with HEV infection, including 20 patients with chronic hepatitis E.<br><br>RESULTS: High tacrolimus trough concentration at diagnosis was the most relevant marker associated with chronic hepatitis E (9.2 vs. 6.4 ng/ml, P&#xa0;= 0.04). Most HEV genetic changes selected during HEV infection were compartmentalized between plasma and feces.<br><br>CONCLUSION: This compartmentalization highlights the diversity and complexity of HEV replication compartments. Tacrolimus trough concentration at diagnosis of HEV infection could allow an early identification of patients at high risk of chronic hepatitis E and guide treatment initiation.}, }
@article {pmid38702466, year = {2024}, author = {Ferreira, J}, title = {Effects of microbiome transplants on fly microbiome.}, journal = {Lab animal}, volume = {53}, number = {5}, pages = {109}, doi = {10.1038/s41684-024-01369-4}, pmid = {38702466}, issn = {1548-4475}, mesh = {Animals ; *Microbiota ; Drosophila melanogaster/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; }, }
@article {pmid38701935, year = {2024}, author = {Xiao, K and Li, H and Li, Y and Zhan, B and Fang, X and Zhao, B and Zhang, X and Wu, Y and Wang, F and Jia, Y}, title = {Protective effects and mechanism of Sangyu granule on acetaminophen-induced liver injury in mice.}, journal = {Journal of ethnopharmacology}, volume = {331}, number = {}, pages = {118282}, doi = {10.1016/j.jep.2024.118282}, pmid = {38701935}, issn = {1872-7573}, mesh = {Animals ; *Acetaminophen/toxicity ; *Chemical and Drug Induced Liver Injury/prevention &amp; control/drug therapy ; *Drugs, Chinese Herbal/pharmacology ; Male ; *Liver/drug effects/metabolism/pathology ; Mice ; *PPAR alpha/metabolism ; *Gastrointestinal Microbiome/drug effects ; Fibroblast Growth Factors ; Cholesterol 7-alpha-Hydroxylase/metabolism/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Tumor Necrosis Factor-alpha/metabolism/blood ; Bile Acids and Salts/metabolism ; Interleukin-1beta/metabolism/genetics ; }, abstract = {The Sang Yu granule (SY), a traditional Chinese medicine prescription of Xijing Hospital, was developed based on the Guanyin powder in the classical prescription "Hong's Collection of Proven Prescriptions" and the new theory of modern Chinese medicine. It has been proved to have a certain therapeutic effect on drug-induced liver injury (DILI), but the specific mechanism of action is still unclear.<br><br>AIM OF STUDY: Aim of the study was to explore the effect of SangYu granule on treating drug-induced liver injury induced by acetaminophen in mice.<br><br>MATERIALS AND METHODS: The chemical composition of SY, serum, and liver tissue was analyzed using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. To assess hepatic function, measurements were taken using kits for total bile acids, as well as serum AST, ALT, and ALP activity. Concentrations of IL-1&#x3b2; and TNF-&#x3b1; in serum were quantified using ELISA kits. Transcriptome Sequencing Analysis and 2bRAD-M microbial diversity analysis were employed to evaluate gene expression variance in liver tissue and fecal microbiota diversity among different groups, respectively. Western blotting was performed to observe differences in the activation levels of FXR, SHP, CYP7A1 and PPAR&#x3b1; in the liver, and the levels of FXR and FGF-15 genes and proteins in the ileum of mice. Additionally, fecal microbiota transplantation (FMT) experiments were conducted to investigate the potential therapeutic effect of administering the intestinal microbial suspension from mice treated with SY on drug-induced liver injury.<br><br>RESULTS: SY treatment exhibited significant hepatoprotective effects in mice, effectively ameliorating drug-induced liver injury while concurrently restoring intestinal microbial dysbiosis. Furthermore, SY administration demonstrated a reduction in the concentration of total bile acids, the expression of FXR and SHP proteins in the liver was up-regulated, CYP7A1 protein was down-regulated, and the expressions of FXR and FGF-15 proteins in the ileum were up-regulated. However, no notable impact on PPAR&#x3b1; was observed. Furthermore, results from FMT experiments indicated that the administration of fecal suspensions derived from mice treated with SY did not yield any therapeutic benefits in the context of drug-induced liver injury.<br><br>CONCLUSION: The aforementioned findings strongly suggest that SY exerts a pronounced ameliorative effect on drug-induced liver injury through its ability to modulate the expression of key proteins involved in bile acid secretion, thereby preserving hepato-enteric circulation homeostasis.}, }
@article {pmid38701724, year = {2024}, author = {Chang, X and Shen, Y and Yang, M and Yun, L and Liu, Z and Feng, S and Yang, G and Meng, X and Su, X}, title = {Antipsychotic drug-induced behavioral abnormalities in common carp: The potential involvement of the gut microbiota-brain axis.}, journal = {Journal of hazardous materials}, volume = {472}, number = {}, pages = {134444}, doi = {10.1016/j.jhazmat.2024.134444}, pmid = {38701724}, issn = {1873-3336}, mesh = {Animals ; *Carps ; *Gastrointestinal Microbiome/drug effects ; *Antipsychotic Agents/toxicity ; *Behavior, Animal/drug effects ; *Risperidone/toxicity/pharmacology ; *Water Pollutants, Chemical/toxicity ; Olanzapine/toxicity ; Brain-Gut Axis/drug effects ; Swimming ; Social Behavior ; }, abstract = {The effects of antipsychotic drugs on aquatic organisms have received widespread attention owing to their widespread use and continued release in aquatic environments. The toxicological effects of antipsychotics on aquatic organisms, particularly fish, are unexplored, and the underlying mechanisms remain unelucidated. This study aimed to use common carp to explore the effects of antipsychotics (olanzapine [OLA] and risperidone [RIS]) on behavior and the potential mechanisms driving these effects. The fish were exposed to OLA (0.1 and 10 μg/L) and RIS (0.03 and 3 μg/L) for 60 days. Behavioral tests and neurological indicators showed that exposure to antipsychotics could cause behavioral abnormalities and neurotoxicity in common carp. Further, 16 S rRNA sequencing revealed gut microbiota alteration and decreased relative abundance of some strains related to SCFA production after OLA and RIS exposure. Subsequently, a pseudo-sterile common carp model was successfully constructed, and transplantation of the gut microbiota from antipsychotic-exposed fish caused behavioral abnormalities and neurotoxicity in pseudo-sterile fish. Further, SCFA supplementation demonstrated that SCFAs ameliorated the behavioral abnormalities and neurological damage caused by antipsychotic exposure. To our knowledge, the present study is the first to investigate the effects of antipsychotics on various complex behaviors (swimming performance and social behavior) in common carp, highlighting the potential health risks associated with antipsychotic drug-induced neurotoxicity in fish. Although these results do not fully elucidate the mechanisms underlying the effects of antipsychotic drugs on fish behavior, they serve as a valuable initial investigation and form the basis for future research.}, }
@article {pmid38700306, year = {2023}, author = {Abraham, P and Pratap, N}, title = {Dysbiosis in Irritable Bowel Syndrome.}, journal = {The Journal of the Association of Physicians of India}, volume = {71}, number = {9}, pages = {75-81}, doi = {10.59556/japi.71.0353}, pmid = {38700306}, issn = {0004-5772}, mesh = {Humans ; Anti-Bacterial Agents/therapeutic use ; *Dysbiosis/therapy ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Irritable Bowel Syndrome/microbiology/therapy ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The human gut microbiota fosters the development of a dynamic group of microorganisms impacted by diverse variables that include genetics, diet, infection, stress, ingested drugs, such as antibiotics and small intestine bacterial overgrowth (SIBO) as well as the gut microbiota itself. These factors may influence the change in microbial composition, which results in dysbiosis (microbial imbalance) and exposes the gut to pathogenic insults. Dysbiosis is incidental to the etiology of inflammatory diseases such as irritable bowel syndrome (IBS) and metabolic diseases, including type 2 diabetes and obesity. IBS exhibits different symptoms like abdominal pain or discomfort, distention/bloating, and flatulence. To treat IBS, modification of dysregulated gut microbiota can be done using treatment strategies like a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, antibiotics that cannot be absorbed like rifaximin and neomycin, probiotics and prebiotics, and fecal microbiota transplantation (FMT). The remedial modalities in the existing literature have been demonstrated to be efficacious in the prevention and mitigation of IBS. Additionally, newer curative approaches with serum-derived bovine immunoglobulin (SBI) are an effective option. The focal point of the review paper is the pathophysiology of IBS, mainly due to dysbiosis and the various factors that advance dysbiosis. Here, we have also discussed the different treatment strategies targeting dysbiosis that effectively treat IBS. How to cite this article: Abraham P, Pratap N. Dysbiosis in Irritable Bowel Syndrome. J Assoc Physicians India 2023;71(9):75-81.}, }
@article {pmid38699545, year = {2024}, author = {Lamas-Paz, A and Mesquita, M and Garcia-Lacarte, M and Estévez-Vázquez, O and Benedé-Ubieto, R and Gutierrez, AH and Wu, H and Leal Lasalle, H and Vaquero, J and Bañares, R and Martínez-Naves, E and Roa, S and Nevzorova, YA and Jorquera, G and Cubero, FJ}, title = {Fecal microbiota transplantation from female donors restores gut permeability and reduces liver injury and inflammation in middle-aged male mice exposed to alcohol.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1393014}, pmid = {38699545}, issn = {2296-861X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Alcohol misuse, binge drinking pattern, and gender-specific effects in the middle-aged population has been clearly underestimated. In the present study, we focused on understanding gender-specific effects of alcohol exposure on the gut-liver axis and the role of gut microbiota in modulating gender-specific responses to alcohol consumption.<br><br>METHODS: Fifty-two-week-old female and male C57BL/6 mice were fasted for 12 h, and then administered a single oral dose of ethanol (EtOH) (6 g/kg). Controls were given a single dose of PBS. Animals were sacrificed 8 h later. Alternatively, fecal microbiota transplantation (FMT) was performed in 52-week-old male mice from female donors of the same age. Permeability of the large intestine (colon), gut microbiota, liver injury, and inflammation was thoroughly evaluated in all groups.<br><br>RESULTS: Middle-aged male mice exposed to EtOH showed a significant increase in gut permeability in the large intestine, evaluated by FITC-dextran assay and ZO-1, OCCLUDIN and MUCIN-2 immuno-staining, compared to PBS-treated animals, whilst female mice of the same age also increased their gut permeability, but displayed a partially maintained intestinal barrier integrity. Moreover, there was a significant up-regulation of TLRs and markers of hepatocellular injury, cell death (AST, TUNEL-positive cells) and lipid accumulation (ORO) in male mice after EtOH exposure. Interestingly, FMT from female donors to male mice reduced gut leakiness, modified gut microbiota composition, ameliorated liver injury and inflammation, TLR activation and the senescence phenotype of middle-aged mice.<br><br>CONCLUSION: Our findings highlighted the relevance of gender in middle-aged individuals who are exposed to alcohol in the gut-liver axis. Moreover, our study revealed that gender-specific microbiota transplantation might be a plausible therapy in the management of alcohol-related disorders during aging.}, }
@article {pmid38698178, year = {2024}, author = {Liao, C and Rolling, T and Djukovic, A and Fei, T and Mishra, V and Liu, H and Lindberg, C and Dai, L and Zhai, B and Peled, JU and van den Brink, MRM and Hohl, TM and Xavier, JB}, title = {Oral bacteria relative abundance in faeces increases due to gut microbiota depletion and is linked with patient outcomes.}, journal = {Nature microbiology}, volume = {9}, number = {6}, pages = {1555-1565}, pmid = {38698178}, issn = {2058-5276}, support = {R37 AI093808/AI/NIAID NIH HHS/United States ; R01 AI139632/AI/NIAID NIH HHS/United States ; R21 AI156157/AI/NIAID NIH HHS/United States ; U54 CA209975/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI093808/AI/NIAID NIH HHS/United States ; RO-5328/1-2 (T.R.)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome ; *Feces/microbiology ; Humans ; Animals ; Mice ; *Bacteria/classification/genetics/isolation &amp; purification ; *RNA, Ribosomal, 16S/genetics ; *Dysbiosis/microbiology ; *Mouth/microbiology ; Colitis/microbiology ; Disease Models, Animal ; Inflammatory Bowel Diseases/microbiology ; Anti-Bacterial Agents/pharmacology ; Mice, Inbred C57BL ; Female ; Dextran Sulfate ; }, abstract = {The detection of oral bacteria in faecal samples has been associated with inflammation and intestinal diseases. The increased relative abundance of oral bacteria in faeces has two competing explanations: either oral bacteria invade the gut ecosystem and expand (the 'expansion' hypothesis), or oral bacteria transit through the gut and their relative increase marks the depletion of other gut bacteria (the 'marker' hypothesis). Here we collected oral and faecal samples from mouse models of gut dysbiosis (antibiotic treatment and DSS-induced colitis) and used 16S ribosomal RNA sequencing to determine the abundance dynamics of oral bacteria. We found that the relative, but not absolute, abundance of oral bacteria increases, reflecting the 'marker' hypothesis. Faecal microbiome datasets from diverse patient cohorts, including healthy individuals and patients with allogeneic haematopoietic cell transplantation or inflammatory bowel disease, consistently support the 'marker' hypothesis and explain associations between oral bacterial abundance and patient outcomes consistent with depleted gut microbiota. By distinguishing between the two hypotheses, our study guides the interpretation of microbiome compositional data and could potentially identify cases where therapies are needed to rebuild the resident microbiome rather than protect against invading oral bacteria.}, }
@article {pmid38697851, year = {2024}, author = {Wu, T and Li, L and Zhou, W and Bi, G and Jiang, X and Guo, M and Yang, X and Fang, J and Pang, J and Fan, S and Bi, H}, title = {Gut Microbiota Affects Mouse Pregnane X Receptor Agonist Pregnenolone 16α-Carbonitrile-Induced Hepatomegaly by Regulating Pregnane X Receptor and Yes-Associated Protein Activation.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {52}, number = {7}, pages = {597-605}, doi = {10.1124/dmd.123.001604}, pmid = {38697851}, issn = {1521-009X}, mesh = {Animals ; *Hepatomegaly/chemically induced/metabolism ; *Pregnane X Receptor/agonists/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Pregnenolone Carbonitrile/pharmacology ; *Mice, Inbred C57BL ; *YAP-Signaling Proteins/metabolism ; Male ; *Fecal Microbiota Transplantation/methods ; Liver/drug effects/metabolism ; }, abstract = {Pregnane X receptor (PXR) is essential in the regulation of liver homeostasis, and the gut microbiota is closely linked to liver physiologic and pathologic status. We previously found that activation of PXR significantly promotes liver enlargement through interaction with yes-associated protein (YAP). However, whether gut microbiota contributes to PXR-induced hepatomegaly and the involved mechanisms remain unclear. In this study, C57BL/6 mice were administered the mouse-specific agonist pregnenolone 16α-carbonitrile (PCN) for 5 days. Depletion of gut microbiota was achieved using broad-spectrum antibiotics (ABX) and fecal microbiota transplantation (FMT) was performed to restore the gut microbia. The composition of gut microbiota was analyzed by 16S rRNA sequencing, while the expression of PXR, YAP, and their downstream target genes and proteins were assessed. The results indicated that PCN treatment altered the composition and abundance of specific bacterial taxa. Furthermore, depletion of gut microbiota using ABX significantly attenuated PCN-induced hepatomegaly. FMT experiments further demonstrated that the fecal microbiota from PCN-treated mice could induce liver enlargement. Mechanistic studies revealed that ABX treatment impeded the PXR and YAP activation induced by PCN, as evidenced by decreased expression of PXR, YAP, and their downstream targets. Moreover, alterations in PXR and YAP activation were likely contributing to hepatomegaly in recipient mice following FMT from PCN-treated mice. Collectively, the current study demonstrated that gut microbiota is involved in PCN-induced hepatomegaly via regulating PXR and YAP activation, providing potential novel insights into the involvement of gut microbiota in PXR-mediated hepatomegaly. SIGNIFICANCE STATEMENT: This work describes that the composition of gut microbiota is altered in mouse pregnane X receptor (PXR) agonist pregnenolone 16α-carbonitrile (PCN)-induced hepatomegaly. Treatment with an antibiotic cocktail depletes the intestinal microbiota, leading to the impairment of liver enlargement caused by PCN. Additionally, fecal microbiota transplantation from PCN-treated mice induces liver enlargement. Further study revealed that gut microbiota is involved in hepatomegaly via regulating PXR and yes-associated protein activation.}, }
@article {pmid38697391, year = {2024}, author = {Soueges, S and Cheynet, V and Briot, T and Merveilleux du Vignaux, C and Benech, N and Ader, F}, title = {Clinical remission after faecal microbiota transplantation in transplanted recipients with refractory chronic Norovirus infections: a retrospective case series.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {8}, pages = {1083-1085}, doi = {10.1016/j.cmi.2024.04.015}, pmid = {38697391}, issn = {1469-0691}, mesh = {Humans ; *Caliciviridae Infections/therapy ; *Fecal Microbiota Transplantation/methods ; Retrospective Studies ; Male ; Female ; Middle Aged ; *Norovirus ; Adult ; Chronic Disease ; Transplant Recipients ; Treatment Outcome ; Aged ; Gastroenteritis/virology/microbiology/therapy ; }, }
@article {pmid38697207, year = {2024}, author = {Tapasco-Tapasco, LO and Gonzalez-Correa, CA and Letourneur, A}, title = {Phase angle and impedance ratio as meta-inflammation biomarkers after a colon cleansing protocol in a group of overweight young women.}, journal = {Physiological measurement}, volume = {45}, number = {5}, pages = {}, doi = {10.1088/1361-6579/ad46df}, pmid = {38697207}, issn = {1361-6579}, mesh = {Humans ; Female ; *Biomarkers/blood/metabolism ; *Overweight ; Young Adult ; *Inflammation ; *Colon/metabolism ; *Electric Impedance ; C-Reactive Protein/metabolism/analysis ; }, abstract = {Objective. Blood C-reactive protein (CRP) and the electrical bioimpedance spectroscopy (EBIS) variables phase angle (PhA) and impedance ratio (IR) have been proposed as biomarkers of metainflammation in overweight/obesity. CRP involves taking blood samples, while PhA and IR imply a less-than-2-minute-non-invasive procedure. In this study, values for these variables and percent body fat mass (PBFM) were obtained and compared before and immediately after a colon cleansing protocol (CCP), aimed at modulating intestinal microbiota and reducing metainflammation, as dysbiosis and the latter are intrinsically related, as well as along a period of 8 weeks after it.Approach. 20 female volunteers (20.9-24.9 years old) participated: 12 in an overweight group (OG), and 8 in a lean group (LG). TheOGwas divided in two subgroups (n= 6, each): control (CSG) and experimental (ESG). TheESGunderwent a 6-day CCP at week 2, while 5 volunteers in theCSGunderwent it at week 9.Main results.Pre/post-CCP mean values for the variables in theOGwere: PBFM (34.3/31.3%), CRP (3.7/0.6 mg dl[-1]), PhA (6.9/7.5°) and IR*10 (0.78/0.77). CalculatedR[2]correlation factors among these variables are all above 0.89. The favourable changes first seen in theESGwere still present 8 weeks after the CCP.Significance.(a) the CCP drastically lowers meta-inflammation, (b) EBIS can be used to measure metainflammation, before and after treatment, (c) for microbiota modulation, CCP could be a good alternative to more drastic procedures like faecal microbiota transplantation; (d) reestablishing eubiosis by CCP could be an effective coadjutant in the treatment of overweight young adult women.}, }
@article {pmid38696921, year = {2024}, author = {Mao, Q and Zhang, H and Zhang, Z and Lu, Y and Pan, J and Guo, D and Huang, L and Tian, H and Ma, K}, title = {Co-decoction of Lilii bulbus and Radix Rehmannia Recens and its key bioactive ingredient verbascoside inhibit neuroinflammation and intestinal permeability associated with chronic stress-induced depression via the gut microbiota-brain axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {129}, number = {}, pages = {155510}, doi = {10.1016/j.phymed.2024.155510}, pmid = {38696921}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Rehmannia/chemistry ; *Glucosides/pharmacology ; *Brain-Gut Axis/drug effects ; *Depression/drug therapy ; Male ; *Neuroinflammatory Diseases/drug therapy ; *Antidepressive Agents/pharmacology ; *Phenols/pharmacology ; Mice ; Stress, Psychological/drug therapy ; Disease Models, Animal ; Permeability ; Rats ; Brain/drug effects ; Mice, Inbred C57BL ; Intestinal Barrier Function ; Polyphenols ; }, abstract = {BACKGROUND: Gut microbiota plays a critical role in the pathogenesis of depression and are a therapeutic target via maintaining the homeostasis of the host through the gut microbiota-brain axis (GMBA). A co-decoction of Lilii bulbus and Radix Rehmannia Recens (LBRD), in which verbascoside is the key active ingredient, improves brain and gastrointestinal function in patients with depression. However, in depression treatment using verbascoside or LBRD, mechanisms underlying the bidirectional communication between the intestine and brain via the GMBA are still unclear.<br><br>PURPOSE: This study aimed to examine the role of verbascoside in alleviating depression via gut-brain bidirectional communication and to study the possible pathways involved in the GMBA.<br><br>METHODS: Key molecules and compounds involved in antidepressant action were identified using HPLC and transcriptomic analyses. The antidepressant effects of LBRD and verbascoside were observed in chronic stress induced depression model by behavioural test, neuronal morphology, and synaptic dendrite ultrastructure, and their neuroprotective function was measured in corticosterone (CORT)-stimulated nerve cell injury model. The causal link between the gut microbiota and the LBRD and verbascoside antidepressant efficacy was evaluate via gut microbiota composition analysis and faecal microbiota transplantation (FMT).<br><br>RESULTS: LBRD and Verbascoside administration ameliorated depression-like behaviours and synaptic damage by reversing gut microbiota disturbance and inhibiting inflammatory responses as the result of impaired intestinal permeability or blood-brain barrier leakiness. Furthermore, verbascoside exerted neuroprotective effects against CORT-induced cytotoxicity in an in vitro depression model. FMT therapy indicated that verbascoside treatment attenuated gut inflammation and central nervous system inflammatory responses, as well as eliminated neurotransmitter and brain-gut peptide deficiencies in the prefrontal cortex by modulating the composition of gut microbiota. Lactobacillus, Parabacteroides, Bifidobacterium, and Ruminococcus might play key roles in the antidepressant effects of LBRD via the GMBA.<br><br>CONCLUSION: The current study elucidates the multi-component, multi-target, and multi-pathway therapeutic effects of LBRD on depression by remodeling GMBA homeostasis and further verifies the causality between gut microbiota and the antidepressant effects of verbascoside and LBRD.}, }
@article {pmid38694925, year = {2024}, author = {Elford, JD and Becht, N and Garssen, J and Kraneveld, AD and Perez-Pardo, P}, title = {Buty and the beast: the complex role of butyrate in Parkinson's disease.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1388401}, pmid = {38694925}, issn = {1663-9812}, abstract = {Parkinson's disease (PD) is a complex neurodegenerative disease which is often associated with gastrointestinal (GI) dysfunction. The GI tract is home to a wide range of microorganisms, among which bacteria, that can influence the host through various mechanisms. Products produced by these bacteria can act in the gut but can also exert effects in the brain via what is now well established to be the microbiota-gut-brain axis. In those with PD the gut-bacteria composition is often found to be different to that of non-PD individuals. In addition to compositional changes, the metabolic activity of the gut-microbiota is also changed in PD. Specifically, it is often reported that key producers of short chain fatty acids (SCFAs) as well as the concentration of SCFAs themselves are altered in the stool and blood of those with PD. These SCFAs, among which butyrate, are essential nutrients for the host and are a major energy source for epithelial cells of the GI tract. Additionally, butyrate plays a key role in regulating various host responses particularly in relation to inflammation. Studies have demonstrated that a reduction in butyrate levels can have a critical role in the onset and progression of PD. Furthermore, it has been shown that restoring butyrate levels in those with PD through methods such as probiotics, prebiotics, sodium butyrate supplementation, and fecal transplantation can have a beneficial effect on both motor and non-motor outcomes of the disease. This review presents an overview of evidence for the altered gut-bacteria composition and corresponding metabolite production in those with PD, with a particular focus on the SCFA butyrate. In addition to presenting current studies regarding SCFA in clinical and preclinical reports, evidence for the possibility to target butyrate production using microbiome based approaches in a therapeutic context is discussed.}, }
@article {pmid38694298, year = {2024}, author = {Shariff, S and Kwan Su Huey, A and Parag Soni, N and Yahia, A and Hammoud, D and Nazir, A and Uwishema, O and Wojtara, M}, title = {Unlocking the gut-heart axis: exploring the role of gut microbiota in cardiovascular health and disease.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {5}, pages = {2752-2758}, pmid = {38694298}, issn = {2049-0801}, abstract = {INTRODUCTION: Gut microbiota has emerged as a pivotal player in cardiovascular health and disease, extending its influence beyond the gut through intricate metabolic processes and interactions with the immune system. Accumulating evidence supports a significant association between gut microbiota and cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Dietary patterns have been identified as key factors shaping the composition of the gut microbiota and exerting notable impacts on cardiovascular health. Probiotics and prebiotics have shown promise in mitigating the risks of cardiovascular disease by modulating key cardiovascular parameters. Faecal microbiota transplantation (FMT) has recently emerged as a novel and intriguing therapeutic strategy.<br><br>AIM: This review paper aims to explore and elucidate the multifaceted role of gut microbiota in cardiovascular health. It will also address the prevailing challenges and limitations in gut microbiota studies, emphasizing the importance of future research in overcoming these obstacles to expand our understanding of the gut-heart axis.<br><br>MATERIALS AND METHODS: A comprehensive literature search was conducted using various databases including ClinicalTrials, Google Scholar, PubMed, ScienceDirect, MEDLINE, and Ovid Resources. The search strategy included utilizing keywords such as "Gut microbiota," "Randomized controlled trials (RCTs)," "Gut-heart axis," "Dysbiosis," "Diet," "Probiotics," "Prebiotics," "Faecal Microbiota transplantation," "cardiovascular disease," "Meta-analyses," and other compatible terms thereof. Only articles written in English were considered, and selection criteria included relevance to the research objectives, reasonable sample sizes, and robust methodology. In addition to the identified articles, meta-analyses, animal models and studies, and references from the selected articles were also examined to ensure a comprehensive review of the literature.<br><br>RESULTS: Dietary patterns exert a significant influence on the composition of the gut microbiota, and certain diets, such as the Mediterranean diet, have been associated with a favourable gut microbiota profile and a reduced risk of cardiovascular disease (CVD). Probiotics and prebiotics have emerged as potential interventions to mitigate CVD risks by modulating blood pressure, glycemic control, lipid profiles, and gut dysbiosis. Another innovative therapeutic approach is FMT, which involves transferring faecal material from a healthy donor to restore a balanced gut microbiota. FMT holds promise for improving cardiometabolic parameters in individuals with CVD, although further research is needed to elucidate its precise mechanisms and assess its effectiveness.<br><br>CONCLUSION: The gut microbiota is emerging as a potential therapeutic target for CVD prevention and management. However, current research has limitations, including the need for larger and more diverse studies, the challenges of establishing causality, and concerns regarding the long-term consequences and safety of gut microbiota modulation. Despite these limitations, understanding the gut-heart axis holds promise for the development of personalized therapies and interventions for cardiovascular health. Further research is needed to expand our knowledge and address the ethical and safety issues associated with gut microbiota modification.}, }
@article {pmid38691831, year = {2024}, author = {Chen, H and Yu, Z and Qi, Z and Huang, X and Gao, J}, title = {Tongfu Lifei Decoction Attenuated Sepsis-Related Intestinal Mucosal Injury Through Regulating Th17/Treg Balance and Modulating Gut Microbiota.}, journal = {Journal of interferon &amp; cytokine research : the official journal of the International Society for Interferon and Cytokine Research}, volume = {44}, number = {5}, pages = {208-220}, doi = {10.1089/jir.2024.0001}, pmid = {38691831}, issn = {1557-7465}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Sepsis/immunology/drug therapy/complications ; *Th17 Cells/immunology/drug effects ; Rats ; *Drugs, Chinese Herbal/pharmacology ; *T-Lymphocytes, Regulatory/immunology/drug effects ; *Intestinal Mucosa/drug effects/immunology/pathology/microbiology ; Male ; Rats, Sprague-Dawley ; }, abstract = {Intestinal damage and secondary bacterial translocation are caused by the inflammatory response induced by sepsis. Tongfu Lifei (TLF) decoction has a protective effect on sepsis-related gastrointestinal function injury. However, the relation between gut microbiota, immune barrier, and sepsis under the treatment of TLF have not been well clarified yet. Here, rats were subjected to cecal ligation and puncture (CLP) to create a sepsis model. Subsequently, the TLF decoction was given to CLP rats by gavage, fecal microbiota transplantation (FMT), and antibiotic were used as positive control. TLF suppressed the inflammatory response and improved the pathological changes in the intestines of CLP rats. Besides, TLF promoted the balance of the percentage of the Th17 and Treg cells. Intestinal barrier function was also improved by TLF through enhancing ZO-1, and Occludin and Claudin 1 expression, preventing the secondary translocation of other gut microbiota. TLF dramatically boosted the gut microbiota's alpha- and beta-diversity in CLP rats. Moreover, it increased the relative abundance of anti-inflammatory gut microbiota and changed the progress of the glucose metabolism. In short, TLF regulated the gut microbiota to balance the ratio of Th17/Treg cells, reducing the inflammation in serum and intestinal mucosal injury in rats.}, }
@article {pmid38690290, year = {2024}, author = {Paudel, D and Nair, DVT and Joseph, G and Castro, R and Tiwari, AK and Singh, V}, title = {Gastrointestinal microbiota-directed nutritional and therapeutic interventions for inflammatory bowel disease: opportunities and challenges.}, journal = {Gastroenterology report}, volume = {12}, number = {}, pages = {goae033}, pmid = {38690290}, issn = {2052-0034}, support = {R01 DK133334/DK/NIDDK NIH HHS/United States ; T32 DK120509/DK/NIDDK NIH HHS/United States ; }, abstract = {Evidence-based research has confirmed the role of gastrointestinal microbiota in regulating intestinal inflammation. These data have generated interest in developing microbiota-based therapies for the prevention and management of inflammatory bowel disease (IBD). Despite in-depth understanding of the etiology of IBD, it currently lacks a cure and requires ongoing management. Accumulating data suggest that an aberrant gastrointestinal microbiome, often referred to as dysbiosis, is a significant environmental instigator of IBD. Novel microbiome-targeted interventions including prebiotics, probiotics, fecal microbiota transplant, and small molecule microbiome modulators are being evaluated as therapeutic interventions to attenuate intestinal inflammation by restoring a healthy microbiota composition and function. In this review, the effectiveness and challenges of microbiome-centered interventions that have the potential to alleviate intestinal inflammation and improve clinical outcomes of IBD are explored.}, }
@article {pmid38690018, year = {2024}, author = {Dai, C and Huang, YH and Jiang, M}, title = {Fecal microbiota transplantation for irritable bowel syndrome: Current evidence and perspectives.}, journal = {World journal of gastroenterology}, volume = {30}, number = {16}, pages = {2179-2183}, pmid = {38690018}, issn = {2219-2840}, mesh = {*Irritable Bowel Syndrome/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; Humans ; Treatment Outcome ; *Gastrointestinal Microbiome ; Feces/microbiology ; Randomized Controlled Trials as Topic ; Clostridioides difficile/pathogenicity ; Clostridium Infections/therapy/microbiology ; }, abstract = {In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology. We focus specifically on the mechanisms un-derlying the effects of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), the factors which affect the outcomes of FMT in IBS patients, and challenges. FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS. The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials, yielding divergent outcomes. The current frontier in this field seeks to elucidate these variations, underscore the existing knowledge gaps that necessitate exploration, and provide a guideline for successful FMT imple-mentation in IBS patients. At the same time, the application of FMT as a treatment for IBS confronts several challenges.}, }
@article {pmid38689371, year = {2024}, author = {Gooch, HCC and Labedan, M and Hall, LJ and Maxwell, A}, title = {Transplanting human infant gut microbiome species into Galleria mellonella.}, journal = {BMC research notes}, volume = {17}, number = {1}, pages = {123}, pmid = {38689371}, issn = {1756-0500}, support = {NC/R001782/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; BB/P012523/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P012523/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P012523/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Humans ; *Moths/microbiology ; *Larva/microbiology ; Infant ; *Feces/microbiology ; Bifidobacterium/isolation &amp; purification ; Enterococcus/isolation &amp; purification ; }, abstract = {OBJECTIVE: Study of the human infant gut microbiome requires the use of surrogate mammalian species such as mice. We sought to investigate the usefulness of the greater wax moth larva, Galleria mellonella, as an alternative.<br><br>RESULTS: We have analysed the native gut microbiome of Galleria and developed methods for clearing the native microbiome and introducing species from human infant faecal samples. We find that some species, e.g. enterococci, are more successful at recolonisation, but that others, e.g. Bifidobacterium, are less so. The work paves the way for using Galleria rather than mice in this and similar work.}, }
@article {pmid38687096, year = {2024}, author = {Song, XL and Liang, J and Lin, SZ and Xie, YW and Ke, CH and Ao, D and Lu, J and Chen, XM and He, YZ and Liu, XH and Li, W}, title = {Gut-lung axis and asthma: A historical review on mechanism and future perspective.}, journal = {Clinical and translational allergy}, volume = {14}, number = {5}, pages = {e12356}, pmid = {38687096}, issn = {2045-7022}, support = {32100602//National Natural Science Foundation of China/ ; 2023A1515012755//Guangdong Natural Science Foundation of China/ ; GCC2021009//Scientific Research Start-up Fund for High-level Talents of Affiliated Hospital of Guangdong Medical University/ ; }, abstract = {BACKGROUND: Gut microbiota are closely related to the development and regulation of the host immune system by regulating the maturation of immune cells and the resistance to pathogens, which affects the host immunity. Early use of antibiotics disrupts the homeostasis of gut microbiota and increases the risk of asthma. Gut microbiota actively interact with the host immune system via the gut-lung axis, a bidirectional communication pathway between the gut and lung. The manipulation of gut microbiota through probiotics, helminth therapy, and fecal microbiota transplantation (FMT) to combat asthma has become a hot research topic. BODY: This review mainly describes the current immune pathogenesis of asthma, gut microbiota and the role of the gut-lung axis in asthma. Moreover, the potential of manipulating the gut microbiota and its metabolites as a treatment strategy for asthma has been discussed.<br><br>CONCLUSION: The gut-lung axis has a bidirectional effect on asthma. Gut microecology imbalance contributes to asthma through bacterial structural components and metabolites. Asthma, in turn, can also cause intestinal damage through inflammation throughout the body. The manipulation of gut microbiota through probiotics, helminth therapy, and FMT can inform the treatment strategies for asthma by regulating the maturation of immune cells and the resistance to pathogens.}, }
@article {pmid38686220, year = {2024}, author = {Bruggeman, A and Vandendriessche, C and Hamerlinck, H and De Looze, D and Tate, DJ and Vuylsteke, M and De Commer, L and Devolder, L and Raes, J and Verhasselt, B and Laukens, D and Vandenbroucke, RE and Santens, P}, title = {Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial.}, journal = {EClinicalMedicine}, volume = {71}, number = {}, pages = {102563}, pmid = {38686220}, issn = {2589-5370}, abstract = {BACKGROUND: Dysregulation of the gut microbiome has been implicated in Parkinson's disease (PD). This study aimed to evaluate the clinical effects and safety of a single faecal microbiota transplantation (FMT) in patients with early-stage PD.<br><br>METHODS: The GUT-PARFECT trial, a single-centre randomised, double-blind, placebo-controlled trial was conducted at Ghent University Hospital between December 01, 2020 and December 12, 2022. Participants (aged 50-65 years, Hoehn and Yahr stage 2) were randomly assigned to receive nasojejunal FMT with either healthy donor stool or their own stool. Computer-generated randomisation was done in a 1:1 ratio through permutated-block scheduling. Treatment allocation was concealed for participants and investigators. The primary outcome measure at 12 months was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score obtained during off-medication evaluations. Intention-to-treat analysis was performed using a mixed model for repeated measures analysis. This completed trial is registered on ClinicalTrials.gov (NCT03808389).<br><br>FINDINGS: Between December 2020 and December 2021, FMT procedures were conducted on 46 patients with PD: 22 in the healthy donor group and 24 in the placebo group. Clinical evaluations were performed at baseline, 3, 6, and 12 months post-FMT. Full data analysis was possible for 21 participants in the healthy donor group and 22 in the placebo group. After 12 months, the MDS-UPDRS motor score significantly improved by a mean of 5.8 points (95% CI&#xa0;-11.4 to&#xa0;-0.2) in the healthy donor group and by 2.7 points (-8.3 to 2.9) in the placebo group (p&#xa0;=&#xa0;0.0235). Adverse events were limited to temporary abdominal discomfort.<br><br>INTERPRETATION: Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages.<br><br>FUNDING: Flemish PD patient organizations (VPL and Parkili), Research Foundation Flanders (FWO), Biocodex Microbiota Foundation.}, }
@article {pmid38685762, year = {2024}, author = {Ishnaiwer, M and Le Bastard, Q and Naour, M and Zeman, M and Dailly, E and Montassier, E and Batard, E and Dion, M}, title = {Efficacy of an inulin-based treatment on intestinal colonization by multidrug-resistant E. coli: insight into the mechanism of action.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2347021}, pmid = {38685762}, issn = {1949-0984}, mesh = {Animals ; *Inulin/pharmacology/metabolism ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Escherichia coli/drug effects/genetics ; *Feces/microbiology ; *Amoxicillin/pharmacology ; *Pantoprazole/pharmacology ; *Drug Resistance, Multiple, Bacterial ; beta-Lactamases/metabolism/genetics ; Dysbiosis/microbiology/drug therapy ; Anti-Bacterial Agents/pharmacology ; Escherichia coli Infections/drug therapy/microbiology ; Female ; Prebiotics/administration &amp; dosage ; }, abstract = {Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by multidrug resistant E. coli and to investigate its potential mechanisms of action. Mice with amoxicillin-induced intestinal dysbiosis mice were inoculated with extended spectrum beta-lactamase producing E. coli (ESBL-E. coli). The combination of inulin and pantoprazole (IP) significantly reduced ESBL-E. coli fecal titers, whereas pantoprazole alone did not and inulin had a delayed and limited effect. Fecal microbiome was assessed using shotgun metagenomic sequencing and qPCR. The efficacy of IP was predicted by increased abundance of 74 taxa, including two species of Adlercreutzia. Preventive treatments with A. caecimuris or A. muris also reduced ESBL-E. coli fecal titers. Fecal microbiota of mice effectively treated by IP was enriched in genes involved in inulin catabolism, production of propionate and expression of beta-lactamases. They also had increased beta-lactamase activity and decreased amoxicillin concentration. These results suggest that IP act through production of propionate and degradation of amoxicillin by the microbiota. The combination of pantoprazole and inulin is a potential treatment of intestinal colonization by multidrug-resistant E. coli. The ability of prebiotics to promote propionate and/or beta-lactamase producing bacteria may be used as a screening tool to identify potential treatments of intestinal colonization by multidrug resistant Enterobacterales.}, }
@article {pmid38685731, year = {2024}, author = {Zhang, Z and Mocanu, V and Deehan, EC and Hotte, N and Zhu, Y and Wei, S and Kao, DH and Karmali, S and Birch, DW and Walter, J and Madsen, KL}, title = {Recipient microbiome-related features predicting metabolic improvement following fecal microbiota transplantation in adults with severe obesity and metabolic syndrome: a secondary analysis of a phase 2 clinical trial.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2345134}, pmid = {38685731}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Metabolic Syndrome/therapy/microbiology ; Male ; Female ; *Gastrointestinal Microbiome ; Adult ; Middle Aged ; *Feces/microbiology ; *Bile Acids and Salts/metabolism/blood ; *Bacteria/classification/isolation &amp; purification/genetics/metabolism ; Obesity/therapy/microbiology ; Dietary Fiber/administration &amp; dosage/metabolism ; Insulin Resistance ; Treatment Outcome ; }, abstract = {Microbial-based therapeutics in clinical practice are of considerable interest, and a recent study demonstrated fecal microbial transplantation (FMT) followed by dietary fiber supplements improved glucose homeostasis. Previous evidence suggests that donor and recipient compatibility and FMT protocol are key determinants, but little is known about the involvement of specific recipient factors. Using data from our recent randomized placebo-control phase 2 clinical trial in adults with obesity and metabolic syndrome, we grouped participants that received FMT from one of 4 donors with either fiber supplement into HOMA-IR responders (n = 21) and HOMA-IR non-responders (n = 8). We further assessed plasma bile acids using targeted metabolomics and performed subgroup analyzes to evaluate the effects of recipient parameters and gastrointestinal factors on microbiota engraftment and homeostatic model assessment of insulin resistance (HOMA2-IR) response. The baseline fecal microbiota composition at genus level of recipients could predict the improvements in HOMA2-IR at week 6 (ROC-AUC = 0.70). Prevotella was identified as an important predictor, with responders having significantly lower relative abundance than non-responders (p = .02). In addition, recipients displayed a highly individualized degree of microbial engraftment from donors. Compared to the non-responders, the responders had significantly increased bacterial richness (Chao1) after FMT and a more consistent engraftment of donor-specific bacteria ASVs (amplicon sequence variants) such as Faecalibacillus intestinalis (ASV44), Roseburia spp. (ASV103), and Christensenellaceae spp. (ASV140) (p < .05). Microbiota engraftment was strongly associated with recipients' factors at baseline including initial gut microbial diversity, fiber and nutrient intakes, inflammatory markers, and bile acid derivative levels. This study identified that responders to FMT therapy had a higher engraftment rate in the transplantation of specific donor-specific microbes, which were strongly correlated with insulin sensitivity improvements. Further, the recipient baseline gut microbiota and related factors were identified as the determinants for responsiveness to FMT and fiber supplementation. The findings provide a basis for the development of precision microbial therapeutics for the treatment of metabolic syndrome.}, }
@article {pmid38684800, year = {2024}, author = {Liu, MT and Zhang, Y and Xiang, CG and Yang, T and Wang, XH and Lu, QK and Lu, HM and Fan, C and Feng, CL and Yang, XQ and Zou, DW and Li, H and Tang, W}, title = {Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages.}, journal = {Acta pharmacologica Sinica}, volume = {45}, number = {9}, pages = {1912-1925}, pmid = {38684800}, issn = {1745-7254}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Methionine/deficiency ; *Macrophages/metabolism/immunology ; Male ; Mice ; *Dextran Sulfate/toxicity ; *Mice, Inbred C57BL ; Humans ; Colitis, Ulcerative/microbiology/pathology/chemically induced/immunology ; Choline Deficiency/complications ; Female ; Diet ; Choline/metabolism ; Colon/pathology/microbiology/immunology ; Colitis/microbiology/pathology/chemically induced ; Liver/pathology/metabolism ; }, abstract = {Ulcerative colitis (UC) is associated with changed dietary habits and mainly linked with the gut microbiota dysbiosis, necroptosis of epithelial cells, and mucosal ulcerations. Liver dysfunction and abnormal level of liver metabolism indices were identified in UC patients, suggesting a close interaction between gut and liver disorders. Methionine-choline deficient diet (MCD) has been shown to induce persistent alterations of gut microbiota and metabolome during hepatitis. In this study we further explored the disease phenotypes in UC patients and investigated whether MCD functioned as a trigger for UC susceptibility. After assessing 88 serum specimens from UC patients, we found significant liver dysfunction and dyslipidemia including abnormal ALT, AST, TG, TC, LDL-c and HDL-c. Liver dysfunction and dyslipidemia were confirmed in DSS-induced colitis mice. We fed mice with MCD for 14 days to cause mild liver damage, and then treated with DSS for 7 days. We found that MCD intake significantly exacerbated the pathogenesis of mucosal inflammation in DSS-induced acute, progressive, and chronic colitis, referring to promotion of mucosal ulcers, colon shortening, diarrhea, inflammatory immune cell infiltration, cytokines release, and abnormal activation of inflammatory macrophages in colon and liver specimens. Intraperitoneal injection of clodronate liposomes to globally delete macrophages dramatically compromised the pathogenesis of MCD-triggering colitis. In addition, MCD intake markedly changed the production pattern of short-chain fatty acids (SCFAs) in murine stools, colons, and livers. We demonstrated that MCD-induced colitis pathogenesis largely depended on the gut microbes and the disease phenotypes could be transmissible through fecal microbiota transplantation (FMT). In conclusion, this study supports the concept that intake of MCD predisposes to experimental colitis and enhances its pathogenesis via modulating gut microbes and macrophages in mice.}, }
@article {pmid38682201, year = {2024}, author = {Ayabe, RI and White, MG}, title = {Metastasis and the Microbiome: The Impact of Bacteria in Disseminated Colorectal Cancer.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {29}, number = {4}, pages = {152}, doi = {10.31083/j.fbl2904152}, pmid = {38682201}, issn = {2768-6698}, support = {T32 CA009599/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Colorectal Neoplasms/microbiology/pathology/therapy ; *Gastrointestinal Microbiome/physiology ; *Neoplasm Metastasis ; Dysbiosis/microbiology ; Bacteria/classification/genetics ; Fecal Microbiota Transplantation ; }, abstract = {Metastasis remains a leading cause of mortality for patients with solid tumors. An expanding body of literature suggests interplay between the host, gut, and tumoral microbiomes may play a role in cancer initiation and distant dissemination. These associations have been particularly well-studied in colorectal cancer, where gut dysbiosis and an endotoxin-induced inflammatory milieu foster premalignant polyp formation, setting the stage for carcinogenesis. Subsequent violation of the gut vascular barrier enables dissemination of bacterial agents to sites such as the liver, where they contribute to establishment of pre-metastatic niches, which promote tumor cell extravasation and metastatic outgrowth. Intriguingly, breakdown of this vascular barrier has been shown to be aided by the presence of tumoral bacteria. The presence of similar species, including Fusobacterium nucleatum and Escherichia Coli, in both primary and metastatic colorectal tumors, supports this hypothesis and their presence is associated with chemotherapy resistance and an overall poor prognosis. Specific gut microbial populations are also associated with differential response to immunotherapy, which has a growing role in microsatellite unstable colorectal cancers. Recent work suggests that modulation of gut microbiome using dietary modification, targeted antibiotics, or fecal microbiota transplantation may improve response to immunotherapy and oncologic outcomes. Elucidation of the precise mechanistic links between the microbiome and cancer dissemination will open the doors to additional therapeutic possibilities.}, }
@article {pmid38680517, year = {2024}, author = {Patel, P and Robinson, PD and Fisher, BT and Phillips, R and Morgan, JE and Lehrnbecher, T and Kuczynski, S and Koenig, C and Haeusler, GM and Esbenshade, A and Elgarten, C and Duong, N and Diorio, C and Castagnola, E and Beauchemin, MP and Ammann, RA and Dupuis, LL and Sung, L}, title = {Guideline for the management of Clostridioides difficile infection in pediatric patients with cancer and hematopoietic cell transplantation recipients: 2024 update.}, journal = {EClinicalMedicine}, volume = {72}, number = {}, pages = {102604}, pmid = {38680517}, issn = {2589-5370}, abstract = {Our objective was to update a clinical practice guideline for the prevention and treatment of Clostridioides difficile infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs. Strong recommendations were made to use either oral metronidazole or oral vancomycin for non-severe CDI treatment, and to use either oral vancomycin or oral fidaxomicin for severe CDI. A strong recommendation that fecal microbiota transplantation should not be routinely used to treat CDI was also made. The panel made two new good practice statements to follow infection control practices including isolation in patients experiencing CDI, and to minimize systemic antibacterial administration where feasible, especially in patients who have experienced CDI.}, }
@article {pmid38679396, year = {2024}, author = {Benech, N and Cassir, N and Galperine, T and Alric, L and Scanzi, J and Sokol, H and , }, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection Can Be the Best Therapeutic Option in Severely Immunocompromised Patients Depending on a Case-by-Case Assessment of the Benefit-to-Risk Ratio.}, journal = {Gastroenterology}, volume = {167}, number = {3}, pages = {627-628}, doi = {10.1053/j.gastro.2024.04.022}, pmid = {38679396}, issn = {1528-0012}, mesh = {Humans ; *Clostridioides difficile ; *Clostridium Infections/therapy/diagnosis/microbiology/immunology ; *Fecal Microbiota Transplantation/adverse effects ; *Immunocompromised Host ; Recurrence ; Risk Assessment ; Treatment Outcome ; }, }
@article {pmid38679228, year = {2024}, author = {Rondinella, D and Quaranta, G and Rozera, T and Dargenio, P and Fancello, G and Venturini, I and Guarnaccia, A and Porcari, S and Bibbò, S and Sanguinetti, M and Gasbarrini, A and Masucci, L and Cammarota, G and Ianiro, G}, title = {Donor screening for fecal microbiota transplantation with a direct stool testing-based strategy: a prospective cohort study.}, journal = {Microbes and infection}, volume = {26}, number = {5-6}, pages = {105341}, doi = {10.1016/j.micinf.2024.105341}, pmid = {38679228}, issn = {1769-714X}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Prospective Studies ; *Feces/microbiology/parasitology ; Female ; Male ; Middle Aged ; *Clostridium Infections/diagnosis/therapy/microbiology ; *Donor Selection/methods ; Aged ; Adult ; Clostridioides difficile/isolation &amp; purification ; Gastrointestinal Microbiome ; }, abstract = {Fecal microbiota transplantation (FMT) is effective against recurrent Clostridioides difficile infection (rCDI), but its safety is jeopardized by the potential transmission of pathogens, so international guidelines recommend either a quarantine or a direct stool testing. Whereas reports of the quarantine-based approach are emerging, data on the direct testing-based approach are not available. Our aim is to report outcomes of a donor screening framework for FMT including direct stool testing. In this prospective cohort study, all donor candidates recruited at our FMT centre underwent a four-step screening process to be enrolled as actual donors. Each collected stool donation was then evaluated with a direct stool testing including a molecular assay for gut pathogens and a culture assay for multi-drug resistant organisms (MDRO). From January 2019 to June 2023, 72 of 227 candidates (32%) were considered eligible and provided 277 stool donations. Ninety-nine donations (36%) were discarded for positivity to intestinal pathogens, most commonly enteropathogenic Escherichia coli (n = 37) and Blastocystis hominis (n = 20). Overall, 337 stool aliquots were obtained from 165 approved donations. All suspensions were used for patients with rCDI, and no serious adverse events or clinically evident infections were observed at 12 weeks after procedures. In our study, screening of donor faeces including direct stool testing led to the discard of a considerable rate of stool donations but was also extremely safe. This approach may represent a reliable strategy to guarantee the safety of FMT programs, especially in countries with high prevalence of MDRO.}, }
@article {pmid38678155, year = {2024}, author = {Corriero, A and Giglio, M and Soloperto, R and Inchingolo, F and Varrassi, G and Puntillo, F}, title = {Microbial Symphony: Exploring the Role of the Gut in Osteoarthritis-Related Pain. A Narrative Review.}, journal = {Pain and therapy}, volume = {13}, number = {3}, pages = {409-433}, pmid = {38678155}, issn = {2193-8237}, abstract = {One of the most common musculoskeletal disorders, osteoarthritis (OA), causes worldwide disability, morbidity, and poor quality of life by degenerating articular cartilage, modifying subchondral bone, and inflaming synovial membranes. OA pathogenesis pathways must be understood to generate new preventative and disease-modifying therapies. In recent years, it has been acknowledged that gut microbiota (GM) can significantly contribute to the development of OA. Dysbiosis of GM can disrupt the "symphony" between the host and the GM, leading to a host immunological response that activates the "gut-joint" axis, ultimately worsening OA. This narrative review summarizes research supporting the "gut-joint axis" hypothesis, focusing on the interactions between GM and the immune system in its two main components, innate and adaptive immunity. Furthermore, the pathophysiological sequence of events that link GM imbalance to OA and OA-related pain is broken down and further investigated. We also suggest that diet and prebiotics, probiotics, nutraceuticals, exercise, and fecal microbiota transplantation could improve OA management and represent a new potential therapeutic tool in the light of the scarce panorama of disease-modifying osteoarthritis drugs (DMOADs). Future research is needed to elucidate these complex interactions, prioritizing how a particular change in GM, i.e., a rise or a drop of a specific bacterial strain, correlates with a certain OA subset to pinpoint the associated signaling pathway that leads to OA.}, }
@article {pmid38676422, year = {2024}, author = {Tang, M and Wang, C and Xia, Y and Tang, J and Wang, J and Shen, L}, title = {Clostridioides difficile infection in inflammatory bowel disease: a clinical review.}, journal = {Expert review of anti-infective therapy}, volume = {22}, number = {5}, pages = {297-306}, doi = {10.1080/14787210.2024.2347955}, pmid = {38676422}, issn = {1744-8336}, mesh = {Humans ; *Clostridium Infections/therapy/microbiology ; *Inflammatory Bowel Diseases/complications/therapy/microbiology ; *Probiotics/administration &amp; dosage ; *Anti-Bacterial Agents/administration &amp; dosage ; Risk Factors ; Fecal Microbiota Transplantation ; Clostridioides difficile/isolation &amp; purification ; Gastrointestinal Microbiome ; Prebiotics/administration &amp; dosage ; Coinfection ; Immunotherapy/methods ; Child ; Prevalence ; Severity of Illness Index ; Age Factors ; Aged ; }, abstract = {INTRODUCTION: Strong clinical data demonstrate that inflammatory bowel disease (IBD) is an independent risk factor for Clostridiodes difficile infection (CDI) and suggest a globally increased prevalence and severity of C. difficile coinfection in IBD patients (CDI-IBD). In addition to elderly individuals, children are also at higher risk of CDI-IBD. Rapid diagnosis is essential since the clinical manifestations of active IBD and CDI-IBD are indistinguishable. Antibiotics have been well established in the treatment of CDI-IBD, but they do not prevent recurrence.<br><br>AREAS COVERED: Herein, the authors focus on reviewing recent research advances on the new therapies of CDI-IBD. The novel therapies include gut microbiota restoration therapies (such as prebiotics, probiotics and FMT), immunotherapy (such as vaccines and monoclonal antibodies) and diet strategies (such as groningen anti-inflammatory diet and mediterranean diet). Future extensive prospective and placebo-controlled studies are required to evaluate their efficacy and long-term safety.<br><br>EXPERT OPINION: Available studies show that the prevalence of CDI-IBD is not optimistic. Currently, potential treatment options for CDI-IBD include a number of probiotics and novel antibiotics. This review updates the knowledge on the management of CDI in IBD patients, which is timely and important for GI doctors and scientists.}, }
@article {pmid38674860, year = {2024}, author = {Wang, X and Jin, Y and Di, C and Zeng, Y and Zhou, Y and Chen, Y and Pan, Z and Li, Z and Ling, W}, title = {Supplementation of Silymarin Alone or in Combination with Salvianolic Acids B and Puerarin Regulates Gut Microbiota and Its Metabolism to Improve High-Fat Diet-Induced NAFLD in Mice.}, journal = {Nutrients}, volume = {16}, number = {8}, pages = {}, pmid = {38674860}, issn = {2072-6643}, support = {81973022//National Natural Science Foundation of China/ ; TY202101003//BYHEALTH Nutrition and Health Research Foundation/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Non-alcoholic Fatty Liver Disease/etiology/drug therapy ; *Diet, High-Fat/adverse effects ; *Mice, Inbred C57BL ; *Isoflavones/pharmacology ; Male ; Mice ; *Silymarin/pharmacology ; *Dietary Supplements ; Benzofurans/pharmacology ; Liver/metabolism/drug effects ; Disease Models, Animal ; Bile Acids and Salts/metabolism ; Plant Extracts/pharmacology ; *Depsides ; }, abstract = {Silymarin, salvianolic acids B, and puerarin were considered healthy food agents with tremendous potential to ameliorate non-alcoholic fatty liver disease (NAFLD). However, the mechanisms by which they interact with gut microbiota to exert benefits are largely unknown. After 8 weeks of NAFLD modeling, C57BL/6J mice were randomly divided into five groups and fed a normal diet, high-fat diet (HFD), or HFD supplemented with a medium or high dose of Silybum marianum extract contained silymarin or polyherbal extract contained silymarin, salvianolic acids B, and puerarin for 16 weeks, respectively. The untargeted metabolomics and 16S rRNA sequencing were used for molecular mechanisms exploration. The intervention of silymarin and polyherbal extract significantly improved liver steatosis and recovered liver function in the mice, accompanied by an increase in probiotics like Akkermansia and Blautia, and suppressed Clostridium, which related to changes in the bile acids profile in feces and serum. Fecal microbiome transplantation confirmed that this alteration of microbiota and its metabolites were responsible for the improvement in NAFLD. The present study substantiated that alterations of the gut microbiota upon silymarin and polyherbal extract intervention have beneficial effects on HFD-induced hepatic steatosis and suggested the pivotal role of gut microbiota and its metabolites in the amelioration of NAFLD.}, }
@article {pmid38674803, year = {2024}, author = {Arteaga-Muller, GY and Flores-Treviño, S and Bocanegra-Ibarias, P and Robles-Espino, D and Garza-González, E and Fabela-Valdez, GC and Camacho-Ortiz, A}, title = {Changes in the Progression of Chronic Kidney Disease in Patients Undergoing Fecal Microbiota Transplantation.}, journal = {Nutrients}, volume = {16}, number = {8}, pages = {}, pmid = {38674803}, issn = {2072-6643}, mesh = {Humans ; *Renal Insufficiency, Chronic/therapy/microbiology ; *Fecal Microbiota Transplantation ; Male ; Female ; *Disease Progression ; Middle Aged ; Double-Blind Method ; *Gastrointestinal Microbiome ; Aged ; *Feces/microbiology ; Dysbiosis/therapy ; Treatment Outcome ; Adult ; Creatinine/blood ; }, abstract = {Chronic kidney disease (CKD) is a progressive loss of renal function in which gut dysbiosis is involved. Fecal microbiota transplantation (FMT) may be a promising alternative for restoring gut microbiota and treating CKD. This study evaluated the changes in CKD progression in patients treated with FMT. Patients with diabetes and/or hypertension with CKD clinical stages 2, 3, and 4 in this single-center, double-blind, randomized, placebo-controlled clinical trial (NCT04361097) were randomly assigned to receive either FMT or placebo capsules for 6 months. Laboratory and stool metagenomic analyses were performed. A total of 28 patients were included (15 FMT and 13 placebo). Regardless of CKD stages, patients responded similarly to FMT treatment. More patients (53.8%) from the placebo group progressed to CKD than the FMT group (13.3%). The FMT group maintained stable renal function parameters (serum creatinine and urea nitrogen) compared to the placebo group. Adverse events after FMT treatment were mild or moderate gastrointestinal symptoms. The abundance of Firmicutes and Actinobacteria decreased whereas Bacteroidetes, Proteobacteria and Roseburia spp. increased in the FMT group. CKD patients showed less disease progression after FMT administration. The administration of oral FMT in patients with CKD is a safe strategy, does not represent a risk, and has potential benefits.}, }
@article {pmid38674209, year = {2024}, author = {Abenavoli, L and Gambardella, ML and Scarlata, GGM and Lenci, I and Baiocchi, L and Luzza, F}, title = {The Many Faces of Metabolic Dysfunction-Associated Fatty Liver Disease Treatment: From the Mediterranean Diet to Fecal Microbiota Transplantation.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {4}, pages = {}, pmid = {38674209}, issn = {1648-9144}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Diet, Mediterranean ; *Non-alcoholic Fatty Liver Disease/therapy/microbiology ; Probiotics/therapeutic use/administration &amp; dosage ; Gastrointestinal Microbiome/physiology ; }, abstract = {The gastrointestinal tract is inhabited by the gut microbiota. The main phyla are Firmicutes and Bacteroidetes. In non-alcoholic fatty liver disease, now renamed metabolic dysfunction-associated fatty liver disease (MAFLD), an alteration in Firmicutes and Bacteroidetes abundance promotes its pathogenesis and evolution into non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. For this reason, early treatment is necessary to counteract its progression. The aim of the present narrative review is to evaluate the different therapeutic approaches to MAFLD. The most important treatment for MAFLD is lifestyle changes. In this regard, the Mediterranean diet could be considered the gold standard in the prevention and treatment of MAFLD. In contrast, a Western diet should be discouraged. Probiotics and fecal microbiota transplantation seem to be valid, safe, and effective alternatives for MAFLD treatment. However, more studies with a longer follow-up and with a larger cohort of patients are needed to underline the more effective approaches to contrasting MAFLD.}, }
@article {pmid38673510, year = {2024}, author = {Bragazzi, MC and Pianigiani, F and Venere, R and Ridola, L}, title = {Dysbiosis in Inflammatory Bowel Disease and Spondyloarthritis: Still a Long Way to Go?.}, journal = {Journal of clinical medicine}, volume = {13}, number = {8}, pages = {}, pmid = {38673510}, issn = {2077-0383}, abstract = {The association between Inflammatory Bowel Disease (IBD) and Spondyloarthritis (SpA) has been known for years, as has the concept that IBD is associated with an altered intestinal bacterial composition, a condition known as "dysbiosis". Recently, a state of intestinal dysbiosis has also been found in SpA. Dysbiosis in the field of IBD has been well characterized so far, as well as in SpA. The aim of this review is to summarize what is known to date and to emphasize the similarities between the microbiota conditions in these two diseases: particularly, an altered distribution in the gut of Enterobacteriaceae, Streptococcus, Haemophilus, Clostridium, Akkermansia, Ruminococcus, Faecalibacterium Prausnitzii, Bacteroides Vulgatus, Dialister Invisus, and Bifidubacterium Adolescentis is common to both IBD and SpA. At the same time, little is known about intestinal dysbiosis in IBD-related SpA. Only a single recent study has found an increase in Escherichia and Shigella abundances and a decrease in Firmicutes, Ruminococcaceae, and Faecalibacterium abundances in an IBD-related SpA group. Based on what has been discovered so far about the altered distribution of bacteria that unite both pathologies, it is appropriate to carry out further studies aiming to improve the understanding of IBD-related SpA for the purpose of developing new therapeutic strategies.}, }
@article {pmid38672797, year = {2024}, author = {Nayak, G and Dimitriadis, K and Pyrpyris, N and Manti, M and Kamperidis, N and Kamperidis, V and Ziakas, A and Tsioufis, K}, title = {Gut Microbiome and Its Role in Valvular Heart Disease: Not a "Gutted" Relationship.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {38672797}, issn = {2075-1729}, abstract = {The role of the gut microbiome (GM) and oral microbiome (OM) in cardiovascular disease (CVD) has been increasingly being understood in recent years. It is well known that GM is a risk factor for various CVD phenotypes, including hypertension, dyslipidemia, heart failure and atrial fibrillation. However, its role in valvular heart disease (VHD) is less well understood. Research shows that, direct, microbe-mediated and indirect, metabolite-mediated damage as a result of gut dysbiosis and environmental factors results in a subclinical, chronic, systemic inflammatory state, which promotes inflammatory cell infiltration in heart valves and subsequently, via pro-inflammatory molecules, initiates a cascade of reaction, resulting in valve calcification, fibrosis and dysfunction. This relationship between GM and VHD adds a pathophysiological link to the pathogenesis of VHD, which can be aimed therapeutically, in order to prevent or regress any risk for valvular pathologies. Therapeutic interventions include dietary modifications and lifestyle interventions, in order to influence environmental factors that can promote gut dysbiosis. Furthermore, the combination of probiotics and prebiotics, as well as fecal m transplantation and targeted treatment with inducers or inhibitors of microbial enzymes have showed promising results in animal and/or clinical studies, with the potential to reduce the inflammatory state and restore the normal gut flora in patients. This review, thus, is going to discuss the pathophysiological links behind the relationship of GM, CVD and VHD, as well as explore the recent data regarding the effect of GM-altering treatment in CVD, cardiac function and systemic inflammation.}, }
@article {pmid38672155, year = {2024}, author = {Shin, J and Baek, GH and Cha, B and Park, SH and Lee, JH and Kim, JS and Kwon, KS}, title = {Complementary Therapeutic Effect of Fecal Microbiota Transplantation in Ulcerative Colitis after the Response to Anti-Tumor Necrosis Factor Alpha Agent Was Lost: A Case Report.}, journal = {Biomedicines}, volume = {12}, number = {4}, pages = {}, pmid = {38672155}, issn = {2227-9059}, support = {2021R1G1A1095241//National Research Foundation of Korea/ ; }, abstract = {In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). Butyricicoccus, Faecalibacterium, Bifidobacterium, Ligilactobacillus, Alistipes, and Odoribacter, which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.}, }
@article {pmid38667013, year = {2024}, author = {Losurdo, G and Mezzapesa, M and Ditonno, I and Piazzolla, M and Pricci, M and Girardi, B and Celiberto, F and Galeano, G and Riezzo, G and Russo, F and Iannone, A and Ierardi, E and Di Leo, A}, title = {Helicobacter pylori Secondary Antibiotic Resistance after One or More Eradication Failure: A Genotypic Stool Analysis Study.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, pmid = {38667013}, issn = {2079-6382}, abstract = {Helicobacter pylori (H. pylori) antibiotic resistance is the leading cause for unsuccessful eradication therapy. After one or more failures, the chance of encountering secondary antibiotic resistance increases. The aim of this study was to characterize genotypic secondary resistance in a cohort of southern Italian H. pylori patients with at least one previous failure. Such patients collected stool samples using a dedicated kit (THD fecal test[TM]), and bacterial DNA was extracted and amplified using RT-PCR. Resistance to clarithromycin, amoxicillin, metronidazole, levofloxacin, and tetracycline was assessed using a high-resolution melting curve. We enrolled 50 patients. A total of 72% of patients failed one previous antibiotic course, 16% failed two, 10% failed three, and 2% failed four. The rate of secondary antibiotic resistance was 16% for clarithromycin, 18% for metronidazole, 14% for amoxicillin, 14% for levofloxacin, and 2% for tetracycline. Among the eight clarithromycin-resistant patients, five (62.5%) previously received a clarithromycin-based regimen. The same rate was 33.3% (3/9) for metronidazole. The only tetracycline-resistant patient had received Pylera. In conclusion, our data seem to show that, even though secondary resistance is not very high, resistance to clarithromycin could be very likely related to previous exposure to this antibiotic.}, }
@article {pmid38666855, year = {2024}, author = {Long, C and Zhou, X and Xia, F and Zhou, B}, title = {Intestinal Barrier Dysfunction and Gut Microbiota in Non-Alcoholic Fatty Liver Disease: Assessment, Mechanisms, and Therapeutic Considerations.}, journal = {Biology}, volume = {13}, number = {4}, pages = {}, pmid = {38666855}, issn = {2079-7737}, support = {2022A1515010833//Natural Science Foundation of Guangdong Province/ ; 82074078//National Natural Science Foundation of China/ ; 81803816//National Natural Science Foundation of China/ ; ZDSYS20220606100801003//Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Re-search/ ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury closely related to insulin resistance (IR) and genetic susceptibility without alcohol consumption, which encompasses a spectrum of liver disorders ranging from simple hepatic lipid accumulation, known as steatosis, to the more severe form of steatohepatitis (NASH). NASH can progress to cirrhosis and hepatocellular carcinoma (HCC), posing significant health risks. As a multisystem disease, NAFLD is closely associated with systemic insulin resistance, central obesity, and metabolic disorders, which contribute to its pathogenesis and the development of extrahepatic complications, such as cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and certain extrahepatic cancers. Recent evidence highlights the indispensable roles of intestinal barrier dysfunction and gut microbiota in the onset and progression of NAFLD/NASH. This review provides a comprehensive insight into the role of intestinal barrier dysfunction and gut microbiota in NAFLD, including intestinal barrier function and assessment, inflammatory factors, TLR4 signaling, and the gut-liver axis. Finally, we conclude with a discussion on the potential therapeutic strategies targeting gut permeability and gut microbiota in individuals with NAFLD/NASH, such as interventions with medications/probiotics, fecal transplantation (FMT), and modifications in lifestyle, including exercise and diet.}, }
@article {pmid38664425, year = {2024}, author = {Chui, ZSW and Chan, LML and Zhang, EWH and Liang, S and Choi, EPH and Lok, KYW and Tun, HM and Kwok, JYY}, title = {Effects of microbiome-based interventions on neurodegenerative diseases: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {9558}, pmid = {38664425}, issn = {2045-2322}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Microbiota ; *Neurodegenerative Diseases/microbiology/therapy ; Probiotics/therapeutic use ; }, abstract = {Neurodegenerative diseases (NDDs) are characterized by neuronal damage and progressive loss of neuron function. Microbiome-based interventions, such as dietary interventions, biotics, and fecal microbiome transplant, have been proposed as a novel approach to managing symptoms and modulating disease progression. Emerging clinical trials have investigated the efficacy of interventions modulating the GM in alleviating or reversing disease progression, yet no comprehensive synthesis have been done. A systematic review of the literature was therefore conducted to investigate the efficacy of microbiome-modulating methods. The search yielded 4051 articles, with 15 clinical trials included. The overall risk of bias was moderate in most studies. Most microbiome-modulating interventions changed the GM composition. Despite inconsistent changes in GM composition, the meta-analysis showed that microbiome-modulating interventions improved disease burden (SMD, - 0.57; 95% CI - 0.93 to - 0.21; I[2] = 42%; P = 0.002) with a qualitative trend of improvement in constipation. However, current studies have high methodological heterogeneity and small sample sizes, requiring more well-designed and controlled studies to elucidate the complex linkage between microbiome, microbiome-modulating interventions, and NDDs.}, }
@article {pmid38664378, year = {2024}, author = {Holmberg, SM and Feeney, RH and Prasoodanan P K, V and Puértolas-Balint, F and Singh, DK and Wongkuna, S and Zandbergen, L and Hauner, H and Brandl, B and Nieminen, AI and Skurk, T and Schroeder, BO}, title = {The gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3502}, pmid = {38664378}, issn = {2041-1723}, support = {2018-02095//Vetenskapsr&#xe5;det (Swedish Research Council)/ ; SMK-1959//Kempestiftelserna (Kempe Foundations)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Dietary Fiber/metabolism ; *Fatty Acids, Volatile/metabolism ; Mice ; *Colon/metabolism/microbiology ; Humans ; *Intestinal Mucosa/metabolism/microbiology ; Male ; Receptors, G-Protein-Coupled/metabolism/genetics ; Female ; Mice, Inbred C57BL ; Mucus/metabolism ; Fecal Microbiota Transplantation ; Symbiosis ; Propionates/metabolism ; Clostridiales/metabolism ; Acetates/metabolism ; Adult ; *Receptors, Cell Surface ; }, abstract = {Beneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the gut bacterial configuration and disturbs this microbe-mucus interaction, but the specific bacteria and microbial metabolites responsible for maintaining mucus function remain poorly understood. By using human-to-mouse microbiota transplantation and ex vivo analysis of colonic mucus function, we here show as a proof-of-concept that individuals who increase their daily dietary fiber intake can improve the capacity of their gut microbiota to prevent diet-mediated mucus defects. Mucus growth, a critical feature of intact colonic mucus, correlated with the abundance of the gut commensal Blautia, and supplementation of Blautia coccoides to mice confirmed its mucus-stimulating capacity. Mechanistically, B. coccoides stimulated mucus growth through the production of the short-chain fatty acids propionate and acetate via activation of the short-chain fatty acid receptor Ffar2, which could serve as a new target to restore mucus growth during mucus-associated lifestyle diseases.}, }
@article {pmid38663650, year = {2024}, author = {Fang, H and Hou, Q and Zhang, W and Su, Z and Zhang, J and Li, J and Lin, J and Wang, Z and Yu, X and Yang, Y and Wang, Q and Li, X and Li, Y and Hu, L and Li, S and Wang, X and Liao, L}, title = {Fecal Microbiota Transplantation Improves Clinical Symptoms of Fibromyalgia: An Open-Label, Randomized, Nonplacebo-Controlled Study.}, journal = {The journal of pain}, volume = {25}, number = {9}, pages = {104535}, doi = {10.1016/j.jpain.2024.104535}, pmid = {38663650}, issn = {1528-8447}, mesh = {Humans ; *Fibromyalgia/therapy ; Female ; Middle Aged ; Adult ; *Fecal Microbiota Transplantation ; Male ; Gastrointestinal Microbiome/physiology ; Treatment Outcome ; }, abstract = {Fibromyalgia (FM) is a complex and poorly understood disorder characterized by chronic and widespread musculoskeletal pain, of which the etiology remains unknown. Now, the disorder of the gut microbiome is considered as one of the main causes of FM. This study aimed to investigate the potential benefits of fecal microbiota transplantation (FMT) in patients with FM. A total of 45 patients completed this open-label, randomized, nonplacebo-controlled clinical study. The numerical rating scale scores in the FMT group were slightly lower than the control group at 1 month (P > .05), and they decreased significantly at 2, 3, 6, and 12 months after treatment (P < .001). Besides, compared with the control group, the Widespread Pain Index, Symptom Severity, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index scores were significantly lower in the FMT group at different time points (P < .001). After 6 months of treatment, there was a significant increase in serotonin (5-hydroxytryptamine) and gamma-aminobutyric acid levels (P < .001), while glutamate levels significantly decreased in the FMT group (P < .001). The total effective rate was higher in the FMT group (90.9%) compared to the control group (56.5%) after 6 months of treatment (P < .05). FMT can effectively improve the clinical symptoms of FM. With the close relations between the changes in neurotransmitters and FM, certain neurotransmitters may serve as a diagnostic marker or potential target for FM patients. PERSPECTIVE: FMT is a novel therapy that aims to restore the gut microbial balance and modulate the gut-brain axis. It is valuable to further explore the therapeutic effect of FMT on FM. Furthermore, certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.}, }
@article {pmid38663540, year = {2024}, author = {Liang, L and Zhang, J and Chen, J and Tian, Y and Li, W and Shi, M and Cheng, S and Zheng, Y and Wang, C and Liu, H and Yang, X and Ye, W}, title = {Bazedoxifene attenuates dextran sodium sulfate-induced colitis in mice through gut microbiota modulation and inhibition of STAT3 and NF-κB pathways.}, journal = {European journal of pharmacology}, volume = {974}, number = {}, pages = {176611}, doi = {10.1016/j.ejphar.2024.176611}, pmid = {38663540}, issn = {1879-0712}, mesh = {Animals ; *Dextran Sulfate ; *NF-kappa B/metabolism ; *STAT3 Transcription Factor/metabolism ; *Colitis/chemically induced/drug therapy/metabolism/microbiology/pathology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Signal Transduction/drug effects ; Indoles/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/drug effects/pathology/metabolism/microbiology ; Male ; Humans ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract for which treatment options remain limited. In this study, we used a dual-luciferase-based screening of an FDA-approved drug library, identifying Bazedoxifene (BZA) as an inhibitor of the NF-κB pathway. We further investigated its therapeutic effects in a dextran sodium sulfate (DSS)-induced colitis model and explored its impact on gut microbiota regulation and the underlying molecular mechanisms. Our results showed that BZA significantly reduced DSS-induced colitis symptoms in mice, evidenced by decreased colon length shortening, lower histological scores, and increased expression of intestinal mucosal barrier-associated proteins, such as Claudin 1, Occludin, Zo-1, Mucin 2 (Muc2), and E-cadherin. Used independently, BZA showed therapeutic effects comparable to those of infliximab (IFX). In addition, BZA modulated the abundance of gut microbiota especially Bifidobacterium pseudolongum, and influenced microbial metabolite production. Crucially, BZA's alleviation of DSS-induced colitis in mice was linked to change in gut microbiota composition, as evidenced by in vivo gut microbiota depletion and fecal microbiota transplantation (FMT) mice model. Molecularly, BZA inhibited STAT3 and NF-κB activation in DSS-induced colitis in mice. In general, BZA significantly reduced DSS-induced colitis in mice through modulating the gut microbiota and inhibiting STAT3 and NF-κB activation, and its independent use demonstrated a therapeutic potential comparable to IFX. This study highlights gut microbiota's role in IBD drug development, offering insights for BZA's future development and its clinical applications.}, }
@article {pmid38663526, year = {2024}, author = {Zhang, S and Tang, S and Liu, Z and Lv, H and Cai, X and Zhong, R and Chen, L and Zhang, H}, title = {Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway.}, journal = {Pharmacological research}, volume = {204}, number = {}, pages = {107194}, doi = {10.1016/j.phrs.2024.107194}, pmid = {38663526}, issn = {1096-1186}, mesh = {Animals ; *Flavonoids/pharmacology/therapeutic use ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Swine ; *MAP Kinase Signaling System/drug effects ; *Lincomycin/pharmacology ; Mice ; Dysbiosis/chemically induced/drug therapy ; Male ; Intestines/drug effects/pathology ; }, abstract = {Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.}, }
@article {pmid38663295, year = {2024}, author = {Liu, A and Li, Y and Li, L and Chen, K and Tan, M and Zou, F and Zhang, X and Meng, X}, title = {Bile acid metabolism is altered in learning and memory impairment induced by chronic lead exposure.}, journal = {Journal of hazardous materials}, volume = {471}, number = {}, pages = {134360}, doi = {10.1016/j.jhazmat.2024.134360}, pmid = {38663295}, issn = {1873-3336}, mesh = {Animals ; *Bile Acids and Salts/metabolism ; *Lead/toxicity ; Male ; *Memory Disorders/chemically induced/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; Hippocampus/metabolism/drug effects ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Maze Learning/drug effects ; Learning/drug effects ; }, abstract = {Lead is a neurotoxic contaminant that exists widely in the environment. Although lead neurotoxicity has been found to be tightly linked to gut microbiota disturbance, the effect of host metabolic disorders caused by gut microbiota disturbance on lead neurotoxicity has not been investigated. In this work, the results of new object recognition tests and Morris water maze tests showed that chronic low-dose lead exposure caused learning and memory dysfunction in mice. The results of 16 S rRNA sequencing of cecal contents and fecal microbiota transplantation showed that the neurotoxicity of lead could be transmitted through gut microbiota. The results of untargeted metabolomics and bile acid targeted metabolism analysis showed that the serum bile acid metabolism profile of lead-exposed mice was significantly changed. In addition, supplementation with TUDCA or INT-777 significantly alleviated chronic lead exposure-induced learning and memory impairment, primarily through inhibition of the NLRP3 inflammasome in the hippocampus to relieve neuroinflammation. In conclusion, our findings suggested that dysregulation of host bile acid metabolism may be one of the mechanisms of lead-induced neurotoxicity, and supplementation of specific bile acids may be a possible therapeutic strategy for lead-induced neurotoxicity.}, }
@article {pmid38660489, year = {2024}, author = {Zhang, J and Wang, H and Liu, Y and Shi, M and Zhang, M and Zhang, H and Chen, J}, title = {Advances in fecal microbiota transplantation for the treatment of diabetes mellitus.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1370999}, pmid = {38660489}, issn = {2235-2988}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; *Diabetes Mellitus/therapy/microbiology ; Dysbiosis/therapy ; Animals ; Feces/microbiology ; }, abstract = {Diabetes mellitus (DM) refers to a group of chronic diseases with global prevalence, characterized by persistent hyperglycemia resulting from various etiologies. DM can harm various organ systems and lead to acute or chronic complications, which severely endanger human well-being. Traditional treatment mainly involves controlling blood sugar levels through replacement therapy with drugs and insulin; however, some patients still find a satisfactory curative effect difficult to achieve. Extensive research has demonstrated a close correlation between enteric dysbacteriosis and the pathogenesis of various types of DM, paving the way for novel therapeutic approaches targeting the gut microbiota to manage DM. Fecal microbiota transplantation (FMT), a method for re-establishing the intestinal microbiome balance, offers new possibilities for treating diabetes. This article provides a comprehensive review of the correlation between DM and the gut microbiota, as well as the current advancements in FMT treatment for DM, using FMT as an illustrative example. This study aims to offer novel perspectives and establish a theoretical foundation for the clinical diagnosis and management of DM.}, }
@article {pmid38659831, year = {2024}, author = {Sall, I and Foxall, R and Felth, L and Maret, S and Rosa, Z and Gaur, A and Calawa, J and Pavlik, N and Whistler, JL and Whistler, CA}, title = {Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38659831}, issn = {2692-8205}, support = {R15 DA058187/DA/NIDA NIH HHS/United States ; T32 MH112507/MH/NIMH NIH HHS/United States ; R21 DA049565/DA/NIDA NIH HHS/United States ; F31 DA056222/DA/NIDA NIH HHS/United States ; P20 GM103506/GM/NIGMS NIH HHS/United States ; }, abstract = {The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.}, }
@article {pmid38659636, year = {2024}, author = {Herman, C and Barker, BM and Bartelli, TF and Chandra, V and Krajmalnik-Brown, R and Jewell, M and Li, L and Liao, C and McAllister, F and Nirmalkar, K and Xavier, JB and Gregory Caporaso, J}, title = {Assessing Engraftment Following Fecal Microbiota Transplant.}, journal = {ArXiv}, volume = {}, number = {}, pages = {}, pmid = {38659636}, issn = {2331-8422}, support = {U24 CA248454/CA/NCI NIH HHS/United States ; }, abstract = {Fecal Microbiota Transplant (FMT) is an FDA approved treatment for recurrent Clostridium difficile infections, and is being explored for other clinical applications, from alleviating digestive and neurological disorders, to priming the microbiome for cancer treatment, and restoring microbiomes impacted by cancer treatment. Quantifying the extent of engraftment following an FMT is important in determining if a recipient didn't respond because the engrafted microbiome didn't produce the desired outcomes (a successful FMT, but negative treatment outcome), or the microbiome didn't engraft (an unsuccessful FMT and negative treatment outcome). The lack of a consistent methodology for quantifying FMT engraftment extent hinders the assessment of FMT success and its relation to clinical outcomes, and presents challenges for comparing FMT results and protocols across studies. Here we review 46 studies of FMT in humans and model organisms and group their approaches for assessing the extent to which an FMT engrafts into three criteria: 1) Chimeric Asymmetric Community Coalescence investigates microbiome shifts following FMT engraftment using methods such as alpha diversity comparisons, beta diversity comparisons, and microbiome source tracking. 2) Donated Microbiome Indicator Features tracks donated microbiome features (e.g., amplicon sequence variants or species of interest) as a signal of engraftment with methods such as differential abundance testing based on the current sample collection, or tracking changes in feature abundances that have been previously identified (e.g., from FMT or disease-relevant literature). 3) Temporal Stability examines how resistant post-FMT recipient's microbiomes are to reverting back to their baseline microbiome. Individually, these criteria each highlight a critical aspect of microbiome engraftment; investigated together, however, they provide a clearer assessment of microbiome engraftment. We discuss the pros and cons of each of these criteria, providing illustrative examples of their application. We also introduce key terminology and recommendations on how FMT studies can be analyzed for rigorous engraftment extent assessment.}, }
@article {pmid38659317, year = {2024}, author = {Xiao, N and He, W and Chen, S and Yao, Y and Wu, N and Xu, M and Du, H and Zhao, Y and Tu, Y}, title = {Protective Effect of Egg Yolk Lipids against Dextran Sulfate Sodium-Induced Colitis: The Key Role of Gut Microbiota and Short-Chain Fatty Acids.}, journal = {Molecular nutrition &amp; food research}, volume = {68}, number = {9}, pages = {e2400048}, doi = {10.1002/mnfr.202400048}, pmid = {38659317}, issn = {1613-4133}, support = {82260642//National Natural Science Foundation of China/ ; 20224ACB205015//Key Program of Natural Science Foundation of Jiangxi Province, China/ ; 29202300002//Training Project of High-level and High-skilled Leading Talents of Jiangxi Province/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Dextran Sulfate ; *Colitis/chemically induced/drug therapy ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Fatty Acids, Volatile/metabolism ; *Mice, Inbred C57BL ; *Egg Yolk ; *Inflammasomes/metabolism/drug effects ; Male ; Mice ; Fecal Microbiota Transplantation ; Colon/drug effects/metabolism/microbiology ; Lipids ; Interleukin-1beta/metabolism ; }, abstract = {Egg yolk lipids significantly alleviate dextran sulfate sodium (DSS)-induced colitis by inhibiting NLRP3 inflammasome, reversing gut microbiota dysbiosis, and increasing short chain fatty acids (SCFAs) concentrations. However, the role of gut microbiota and the relationship between SCFAs and NLRP3 inflammasome are still unknown. Here, this study confirms that antibiotic treatment abolishes the protective effect of egg yolk lipids on DSS-induced colonic inflammation, intestinal barrier damage, and lipopolysaccharide translocation. Fecal microbiota transplantation also supports that egg yolk lipids alleviate colitis in a gut microbiota-dependent manner. Then, the study investigates the relationship between SCFAs and NLRP3 inflammasome, and finds that SCFAs significantly suppress colitis via inhibiting colonic NLRP3 inflammasome activation and proinflammatory cytokines secretions (interleukin, IL)-1β and IL-18, and combined treatment of SCFAs and MCC950 (NLRP3 inhibitor) shows a better activity against colitis and NLRP3 inflammasome activation. Together, these findings provide positive evidence for gut microbiorta-SCFAs-NLRP3 axis as a novel target involving in the therapy of inflammatory bowel disease.}, }
@article {pmid38655401, year = {2024}, author = {Shi, W and Li, Z and Wang, W and Liu, X and Wu, H and Chen, X and Zhou, X and Zhang, S}, title = {Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation.}, journal = {Journal of pharmaceutical analysis}, volume = {14}, number = {4}, pages = {100931}, pmid = {38655401}, issn = {2214-0883}, abstract = {Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis (ICGN). However, an in-depth study on this topic is currently lacking. Herein, we report an ICGN model to address this gap. ICGN was induced via the intravenous injection of cationized bovine serum albumin (c-BSA) into Sprague-Dawley (SD) rats for two weeks, after which mycophenolate mofetil (MMF) and losartan were administered orally. Two and six weeks after ICGN establishment, fecal samples were collected and 16S ribosomal DNA (rDNA) sequencing and untargeted metabolomic were conducted. Fecal microbiota transplantation (FMT) was conducted to determine whether gut normalization caused by MMF and losartan contributed to their renal protective effects. A gradual decline in microbial diversity and richness was accompanied by a loss of renal function. Approximately 18 genera were found to have significantly different relative abundances between the early and later stages, and Marvinbryantia and Allobaculum were markedly upregulated in both stages. Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN, characterized by the overproduction of indole and kynurenic acid, while the serotonin pathway was reduced. Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces. FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes (F/B) ratio but did not improve renal function. These findings indicate that ICGN induces serous gut dysbiosis, wherein an altered tryptophan metabolism may contribute to its progression. MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis, which partially contributed to their renoprotective effects.}, }
@article {pmid38654015, year = {2024}, author = {Lachance, G and Robitaille, K and Laaraj, J and Gevariya, N and Varin, TV and Feldiorean, A and Gaignier, F and Julien, IB and Xu, HW and Hallal, T and Pelletier, JF and Bouslama, S and Boufaied, N and Derome, N and Bergeron, A and Ellis, L and Piccirillo, CA and Raymond, F and Fradet, Y and Labbé, DP and Marette, A and Fradet, V}, title = {The gut microbiome-prostate cancer crosstalk is modulated by dietary polyunsaturated long-chain fatty acids.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3431}, pmid = {38654015}, issn = {2041-1723}, support = {400345//Canadian Cancer Society Research Institute (Soci&#x00E9;t&#x00E9; Canadienne du Cancer)/ ; }, mesh = {Male ; *Gastrointestinal Microbiome ; *Prostatic Neoplasms/metabolism/diet therapy/microbiology ; Animals ; Humans ; Mice ; *Fecal Microbiota Transplantation ; *Feces/microbiology ; Fatty Acids, Omega-3/metabolism/administration &amp; dosage ; Mice, Inbred C57BL ; Fatty Acids, Unsaturated/metabolism ; }, abstract = {The gut microbiota modulates response to hormonal treatments in prostate cancer (PCa) patients, but whether it influences PCa progression remains unknown. Here, we show a reduction in fecal microbiota alpha-diversity correlating with increase tumour burden in two distinct groups of hormonotherapy naïve PCa patients and three murine PCa models. Fecal microbiota transplantation (FMT) from patients with high PCa volume is sufficient to stimulate the growth of mouse PCa revealing the existence of a gut microbiome-cancer crosstalk. Analysis of gut microbial-related pathways in mice with aggressive PCa identifies three enzymes responsible for the metabolism of long-chain fatty acids (LCFA). Supplementation with LCFA omega-3 MAG-EPA is sufficient to reduce PCa growth in mice and cancer up-grading in pre-prostatectomy PCa patients correlating with a reduction of gut Ruminococcaceae in both and fecal butyrate levels in PCa patients. This suggests that the beneficial effect of omega-3 rich diet is mediated in part by modulating the crosstalk between gut microbes and their metabolites in men with PCa.}, }
@article {pmid38653643, year = {2024}, author = {Taghaddos, D and Saqib, Z and Bai, X and Bercik, P and Collins, SM}, title = {Post-infectious ibs following Clostridioides difficile infection; role of microbiota and implications for treatment.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {56}, number = {11}, pages = {1805-1809}, doi = {10.1016/j.dld.2024.03.008}, pmid = {38653643}, issn = {1878-3562}, mesh = {Humans ; *Irritable Bowel Syndrome/microbiology/therapy ; *Clostridium Infections/therapy/microbiology/complications/drug therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Clostridioides difficile ; *Anti-Bacterial Agents/therapeutic use ; Dysbiosis/microbiology ; }, abstract = {Up to 25% of patients recovering from antibiotic-treated Clostridioides difficile infection (CDI) develop functional symptoms reminiscent of Post-Infectious Irritable Bowel Syndrome (PI-IBS). For patients with persistent symptoms following infection, a clinical dilemma arises as to whether to provide additional antibiotic treatment or to adopt a conservative symptom-based approach. Here, we review the literature on CDI-related PI-IBS and compare the findings with PI-IBS. We review proposed mechanisms, including the role of C. difficile toxins and the microbiota, and discuss implications for therapy. We suggest that gut dysfunction post-CDI may be initiated by toxin-induced damage to enteroglial cells and that a dysbiotic gut microbitota maintains the clinical phenotype over time, prompting consideration of microbiota-directed therapies. While Fecal Microbial Transplant (FMT) is currently reserved for recurrent CDI (rCDI), we propose that microbiota-directed therapies may have a role in primary CDI in order to avoid or mitigate futher antibiotic treatment that further disrupts the microbiota and thus prevent PI-IBS. We discuss novel microbial transfer therapies and as they emerge, we recommend clinical trials to determine whether microbial transfer therapy of the primary infection prevents both rCDI and CDI-related PI- IBS.}, }
@article {pmid38651930, year = {2024}, author = {Reygner, J and Delannoy, J and Barba-Goudiaby, M-T and Gasc, C and Levast, B and Gaschet, E and Ferraris, L and Paul, S and Kapel, N and Waligora-Dupriet, A-J and Barbut, F and Thomas, M and Schwintner, C and Laperrousaz, B and Corvaïa, N}, title = {Reduction of product composition variability using pooled microbiome ecosystem therapy and consequence in two infectious murine models.}, journal = {Applied and environmental microbiology}, volume = {90}, number = {5}, pages = {e0001624}, pmid = {38651930}, issn = {1098-5336}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Clostridioides difficile ; *Clostridium Infections/therapy/microbiology ; *Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Feces/microbiology ; Bacteria/classification/genetics ; Humans ; Mice, Inbred C57BL ; Female ; }, abstract = {Growing evidence demonstrates the key role of the gut microbiota in human health and disease. The recent success of microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on its potential in conditions associated with gut dysbiosis, such as acute graft-versus-host disease, intestinal bowel diseases, neurodegenerative diseases, or even cancer. However, the difficulty in defining a "good" donor as well as the intrinsic variability of donor-derived products' taxonomic composition limits the translatability and reproducibility of these studies. Thus, the pooling of donors' feces has been proposed to homogenize product composition and achieve higher taxonomic richness and diversity. In this study, we compared the metagenomic profile of pooled products to corresponding single donor-derived products. We demonstrated that pooled products are more homogeneous, diverse, and enriched in beneficial bacteria known to produce anti-inflammatory short chain fatty acids compared to single donor-derived products. We then evaluated pooled products' efficacy compared to corresponding single donor-derived products in Salmonella and C. difficile infectious mouse models. We were able to demonstrate that pooled products decreased pathogenicity by inducing a structural change in the intestinal microbiota composition. Single donor-derived product efficacy was variable, with some products failing to control disease progression. We further performed in vitro growth inhibition assays of two extremely drug-resistant bacteria, Enterococcus faecium vanA and Klebsiella pneumoniae oxa48, supporting the use of pooled microbiotherapies. Altogether, these results demonstrate that the heterogeneity of donor-derived products is corrected by pooled fecal microbiotherapies in several infectious preclinical models.IMPORTANCEGrowing evidence demonstrates the key role of the gut microbiota in human health and disease. Recent Food and Drug Administration approval of fecal microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on their potential to treat pathological conditions associated with gut dysbiosis. In this study, we combined metagenomic analysis with in vitro and in vivo studies to compare the efficacy of pooled microbiotherapy products to corresponding single donor-derived products. We demonstrate that pooled products are more homogeneous, diverse, and enriched in beneficial bacteria compared to single donor-derived products. We further reveal that pooled products decreased Salmonella and Clostridioides difficile pathogenicity in mice, while single donor-derived product efficacy was variable, with some products failing to control disease progression. Altogether, these findings support the development of pooled microbiotherapies to overcome donor-dependent treatment efficacy.}, }
@article {pmid38648368, year = {2024}, author = {Muchhala, KH and Kallurkar, PS and Kang, M and Koseli, E and Poklis, JL and Xu, Q and Dewey, WL and Fettweis, JM and Jimenez, NR and Akbarali, HI}, title = {The role of morphine- and fentanyl-induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota-gut-brain axis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {38}, number = {8}, pages = {e23603}, pmid = {38648368}, issn = {1530-6860}, support = {P30 DA033934/DA/NIDA NIH HHS/United States ; T32 DA007027/DA/NIDA NIH HHS/United States ; R01 DA024009/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; *Morphine/pharmacology ; Mice ; *Dysbiosis/chemically induced/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Intestinal Mucosa/metabolism/drug effects/microbiology ; Male ; *Fentanyl/pharmacology ; *Analgesics, Opioid/pharmacology ; *Mice, Inbred C57BL ; Brain-Gut Axis/drug effects ; Fecal Microbiota Transplantation ; Pancreatitis-Associated Proteins/metabolism ; Akkermansia/drug effects ; Antimicrobial Peptides/pharmacology ; Bacteroidetes/drug effects ; }, abstract = {Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes intestinal dysbiosis. Depleting gut bacteria can preclude the development of tolerance to opioid-induced antinociception, suggesting an important role of the gut-brain axis in mediating opioid effects. The mechanism underlying opioid-induced dysbiosis, however, remains unclear. Host-produced antimicrobial peptides (AMPs) are critical for the integrity of the intestinal epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that chronic morphine or fentanyl exposure reduces the antimicrobial activity in the ileum, resulting in changes in the composition of bacteria. Fecal samples from morphine-treated mice had increased levels of Akkermansia muciniphila with a shift in the abundance ratio of Firmicutes and Bacteroidetes. Fecal microbial transplant (FMT) from morphine-naïve mice or oral supplementation with butyrate restored (a) the antimicrobial activity, (b) the expression of the antimicrobial peptide, Reg3γ, (c) prevented the increase in intestinal permeability and (d) prevented the development of antinociceptive tolerance in morphine-dependent mice. Improved epithelial barrier function with FMT or butyrate prevented the enrichment of the mucin-degrading A. muciniphila in morphine-dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which opioids disrupt the microbiota-gut-brain axis.}, }
@article {pmid38647627, year = {2023}, author = {Zhuang, X and Zhao, M and Ji, X and Yang, S and Yin, H and Zhao, L}, title = {Chitobiose exhibited a lipid-lowering effect in ob/ob[-/-] mice via butyric acid enrolled liver-gut crosstalk.}, journal = {Bioresources and bioprocessing}, volume = {10}, number = {1}, pages = {79}, pmid = {38647627}, issn = {2197-4365}, support = {23ZR1417300//Shanghai Natural Science Foundation General program/ ; 2022153//Shanghai post-doctoral Excellence Program/ ; 2019YFD090180302//National key R&amp;D Program of China/ ; B18022//111 Project/ ; }, abstract = {Chitobiose (COS2) efficiently lowers lipids in vivo and facilitates butyric acid enrichment during human fecal fermentation. However, whether COS2 can interact with butyric acid to generate a hypolipidemic effect remains unclear. This study examined the hypolipidemic mechanism of COS2 involving butyric acid, which could alleviate non-alcoholic fatty liver disease (NAFLD). The results revealed that COS2 administration modulated the β-oxidation pathway in the liver and restructured the short chain fatty acids in the fecal of ob/ob[-/-] mice. Moreover, the hypolipidemic effect of COS2 and its specific accumulated metabolite butyric acid was verified in sodium oleate-induced HepG2 cells. Butyric acid was more effective to reverse lipid accumulation and up-regulate β-oxidation pathway at lower concentrations. Furthermore, structural analysis suggested that butyric acid formed hydrogen bonds with key residues in hydrophilic ligand binding domains (LBDs) of PPARα and activated the transcriptional activity of the receptor. Therefore, the potential mechanism behind the lipid-lowering effect of COS2 in vivo involved restoring hepatic lipid disorders via butyric acid accumulation and liver-gut axis signaling.}, }
@article {pmid38647957, year = {2024}, author = {Singh, V and Mahra, K and Jung, D and Shin, JH}, title = {Gut Microbes in Polycystic Ovary Syndrome and Associated Comorbidities; Type 2 Diabetes, Non-Alcoholic Fatty Liver Disease (NAFLD), Cardiovascular Disease (CVD), and the Potential of Microbial Therapeutics.}, journal = {Probiotics and antimicrobial proteins}, volume = {16}, number = {5}, pages = {1744-1761}, pmid = {38647957}, issn = {1867-1314}, support = {2021R1A6C101A416//Korea Basic Science Institute/ ; }, mesh = {*Polycystic Ovary Syndrome/microbiology/metabolism/therapy ; Humans ; Female ; *Gastrointestinal Microbiome ; *Non-alcoholic Fatty Liver Disease/microbiology/metabolism/therapy ; *Cardiovascular Diseases/microbiology/etiology/metabolism ; *Diabetes Mellitus, Type 2/microbiology/metabolism ; Dysbiosis/microbiology ; Comorbidity ; Animals ; }, abstract = {Polycystic ovary syndrome (PCOS) is one of the most common endocrine anomalies among females of reproductive age, highlighted by hyperandrogenism. PCOS is multifactorial as it can be associated with obesity, insulin resistance, low-grade chronic inflammation, and dyslipidemia. PCOS also leads to dysbiosis by lowering microbial diversity and beneficial microbes, such as Faecalibacterium, Roseburia, Akkermenisa, and Bifidobacterium, and by causing a higher load of opportunistic pathogens, such as Escherichia/Shigella, Fusobacterium, Bilophila, and Sutterella. Wherein, butyrate producers and Akkermansia participate in the glucose uptake by inducing glucagon-like peptide-1 (GLP-1) and glucose metabolism, respectively. The abovementioned gut microbes also maintain the gut barrier function and glucose homeostasis by releasing metabolites such as short-chain fatty acids (SCFAs) and Amuc_1100 protein. In addition, PCOS-associated gut is found to be higher in gut-microbial enzyme β-glucuronidase, causing the de-glucuronidation of conjugated androgen, making it susceptible to reabsorption by entero-hepatic circulation, leading to a higher level of androgen in the circulatory system. Overall, in PCOS, such dysbiosis increases the gut permeability and LPS in the systemic circulation, trimethylamine N-oxide (TMAO) in the circulatory system, chronic inflammation in the adipose tissue and liver, and oxidative stress and lipid accumulation in the liver. Thus, in women with PCOS, dysbiosis can promote the progression and severity of type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD). To alleviate such PCOS-associated complications, microbial therapeutics (probiotics and fecal microbiome transplantation) can be used without any side effects, unlike in the case of hormonal therapy. Therefore, this study sought to understand the mechanistic significance of gut microbes in PCOS and associated comorbidities, along with the role of microbial therapeutics that can ease the life of PCOS-affected women.}, }
@article {pmid38647087, year = {2024}, author = {Zhou, F and Zhang, Q and Zheng, X and Shi, F and Ma, K and Ji, F and Meng, N and Li, R and Lv, J and Li, Q}, title = {Antiaging Effects of Human Fecal Transplants with Different Combinations of Bifidobacterium bifidum LTBB21J1 and Lactobacillus casei LTL1361 in d-Galactose-Induced Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {17}, pages = {9818-9827}, doi = {10.1021/acs.jafc.3c09815}, pmid = {38647087}, issn = {1520-5118}, mesh = {Animals ; *Lacticaseibacillus casei/metabolism ; Humans ; *Galactose ; Mice ; *Probiotics/administration &amp; dosage/pharmacology ; *Bifidobacterium bifidum/physiology ; *Gastrointestinal Microbiome/drug effects ; *Feces/microbiology/chemistry ; *Aging ; Male ; Fecal Microbiota Transplantation ; Middle Aged ; Female ; Aged ; Mice, Inbred C57BL ; Bacteria/classification/isolation &amp; purification/genetics/metabolism ; }, abstract = {The feces of healthy middle-aged and old people were first transplanted into d-galactose-induced aging mice to construct humanized aging mice with gut microbiota (FMTC) to confirm the antiaging effect of probiotics produced from centenarians. The mouse model was then treated with centenarian-derived Bifidobacterium bifidum (FMTL), Lactobacillus casei (FMTB), and their mixtures (FMTM), and young mice were used as the control. Compared with the FMTC group, the results demonstrated that the probiotics and their combinations alleviated neuronal damage, increased antioxidant capacity, decreased inflammation, and enhanced cognitive and memory functions in aging mice. In the gut microbiota, the relative abundance of Lactobacillus, Ligilactobacillus, and Akkermansia increased and that of Desulfovibrio and Colidextribacter decreased in the FMTM group compared with that in the FMTC group. The three probiotic groups displayed significant changes in 15 metabolites compared with the FMTC group, with 4 metabolites showing increased expression and 11 metabolites showing decreased expression. The groups were graded as Control > FMTM > FMTB > FMTL > FMTC using a newly developed comprehensive quantitative scoring system that thoroughly analyzed the various indicators of this study. The beneficial antiaging effects of probiotics derived from centenarians were quantitatively described using a novel perspective in this study; it is confirmed that both probiotics and their combinations exert antiaging effects, with the probiotic complex group exhibiting a larger effect.}, }
@article {pmid38646653, year = {2024}, author = {Liu, Q and Yang, Y and Pan, M and Yang, F and Yu, Y and Qian, Z}, title = {Role of the gut microbiota in tumorigenesis and treatment.}, journal = {Theranostics}, volume = {14}, number = {6}, pages = {2304-2328}, pmid = {38646653}, issn = {1838-7640}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Carcinogenesis ; *Neoplasms/microbiology/therapy ; *Dysbiosis/microbiology ; Animals ; }, abstract = {The gut microbiota is a crucial component of the intricate microecosystem within the human body that engages in interactions with the host and influences various physiological processes and pathological conditions. In recent years, the association between dysbiosis of the gut microbiota and tumorigenesis has garnered increasing attention, as it is recognized as a hallmark of cancer within the scientific community. However, only a few microorganisms have been identified as potential drivers of tumorigenesis, and enhancing the molecular understanding of this process has substantial scientific importance and clinical relevance for cancer treatment. In this review, we delineate the impact of the gut microbiota on tumorigenesis and treatment in multiple types of cancer while also analyzing the associated molecular mechanisms. Moreover, we discuss the utility of gut microbiota data in cancer diagnosis and patient stratification. We further outline current research on harnessing microorganisms for cancer treatment while also analyzing the prospects and challenges associated with this approach.}, }
@article {pmid38644237, year = {2024}, author = {,  and ,  and , }, title = {[Chinese expert consensus on the clinical diagnosis and treatment of gut microecology in chronic constipation (2024 edition)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {27}, number = {4}, pages = {326-337}, doi = {10.3760/cma.j.cn441530-20240313-00096}, pmid = {38644237}, issn = {1671-0274}, support = {2022YFC2010101//"Thirteenth Five-Year Plan" National Key Research and Development Program "Proactive Health and Aging Science and Technology Response" Key Project/ ; 82100698//National Natural Science Foundation of China/ ; 21Y11908300, 22DZ2203700//Shanghai Municipal Science and Technology Innovation Action Plan/ ; }, mesh = {Humans ; *Constipation/therapy/diagnosis ; *Gastrointestinal Microbiome ; Chronic Disease ; *Fecal Microbiota Transplantation ; China ; *Consensus ; Dysbiosis/therapy/diagnosis ; Quality of Life ; }, abstract = {Chronic constipation is one of the common gastrointestinal disorders, with an incidence rate that is gradually increasing yearly and becoming an important chronic disease that affects people's health and quality of life. In recent years, significant progress has been made in the basic and clinical research of chronic constipation, especially the gut microbiota therapy methods have received increasing attention. Therefore, under the initiative of the Parenteral and Enteral Nutrition Branch of the Chinese Medical Association, Chinese Society for the Promotion of Human Health Science and Technology, and Committee on Gut Microecology and Fecal Microbiota Transplantation, experts from relevant fields in China have been organized to establish the "Chinese Expert Consensus on the Clinical Diagnosis and Treatment of Gut Microecology in Chronic Constipation (2024 Edition)" committee. Focusing on the dysbiosis of gut microbiota, the indications for gut microbiota therapy, and the protocols for fecal microbiota transplantation, 16 consensus opinions were proposed based on the review of domestic and international literature and the clinical experience of experts, aiming to standardize the clinical application of gut microbiota in chronic constipation.}, }
@article {pmid38642272, year = {2024}, author = {Chen, LA and Boyle, K}, title = {The Role of the Gut Microbiome in Health and Disease in the Elderly.}, journal = {Current gastroenterology reports}, volume = {26}, number = {9}, pages = {217-230}, pmid = {38642272}, issn = {1534-312X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Aged ; *Fecal Microbiota Transplantation ; Aging/physiology ; Healthy Aging/physiology ; }, abstract = {PURPOSE OF REVIEW: Growing evidence supports the contribution of age in the composition and function of the gut microbiome, with specific findings associated with health in old age and longevity.<br><br>RECENT FINDINGS: Current studies have associated certain microbiota, such as Butyricimonas, Akkermansia, and Odoribacter, with healthy aging and the ability to survive into extreme old age. Furthermore, emerging clinical and pre-clinical research have shown promising mechanisms for restoring a healthy microbiome in elderly populations through various interventions such as fecal microbiota transplant (FMT), dietary interventions, and exercise programs. Despite several conceptually exciting interventional studies, the field of microbiome research in the elderly remains limited. Specifically, large longitudinal studies are needed to better understand causative relationships between the microbiome and healthy aging. Additionally, individualized approaches to microbiome interventions based on patients' co-morbidities and the underlying functional capacity of their microbiomes are needed to achieve optimal results.}, }
@article {pmid38639049, year = {2024}, author = {Peng, Z and Zhang, J and Zhang, M and Yin, L and Zhou, Z and Lv, C and Wang, Z and Tang, J}, title = {Tryptophan metabolites relieve intestinal Candida albicans infection by altering the gut microbiota to reduce IL-22 release from group 3 innate lymphoid cells of the colon lamina propria.}, journal = {Food &amp; function}, volume = {15}, number = {10}, pages = {5364-5381}, doi = {10.1039/d4fo00432a}, pmid = {38639049}, issn = {2042-650X}, mesh = {Animals ; Mice ; *Candida albicans/drug effects ; *Candidiasis/drug therapy/immunology/microbiology ; *Colon/microbiology/immunology/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Immunity, Innate ; *Interleukin-22/metabolism ; *Interleukins/metabolism ; *Intestinal Mucosa/metabolism/immunology ; Lymphocytes/immunology/metabolism ; Mice, Inbred C57BL ; *Tryptophan/metabolism/pharmacology ; }, abstract = {Invasive candidiasis may be caused by Candida albicans (C. albicans) colonization of the intestinal tract. Preventing intestinal damage caused by Candida albicans infection and protecting intestinal barrier function have become a critical issue. Integrated analyses of the microbiome with metabolome revealed a remarkable shift of the gut microbiota and tryptophan metabolites, kynurenic acid (KynA), and indolacrylic acid (IA) in mice infected with C. albicans. The transcriptome sequencing indicated that differentially expressed genes were significantly associated with innate immune responses and inflammatory responses. The results of this study suggest that KynA and IA (KI) can alleviate intestinal damage caused by Candida albicans infection in mice by reducing intestinal permeability, increasing intestinal firmness, alleviating intestinal inflammation, and reducing the secretion of interleukin-22 (IL-22) in the 3 groups of colon innate lymphoid cells (ILC3). We performed a fecal microbiota transplantation (FMT) experiment and found that the intestinal barrier function, inflammation, and IL-22 secretion of ILC3 in the colon lamina propria of the recipient mice subjected to C. albicans infection and KI treatment were consistent with the trends of the donor mice. Our results suggest that tryptophan metabolites may directly regulate colon lamina ILC3 to promote intestinal resistance to C. albicans invasion, or indirectly regulate the ILC3 secretion of IL-22 to play a protective role in the intestinal barrier by affecting intestinal microorganisms, which may become a potential target for alleviating intestine borne C. albicans infection.}, }
@article {pmid38638595, year = {2024}, author = {Srikrishnaraj, A and Lanting, BA and Burton, JP and Teeter, MG}, title = {The Microbial Revolution in the World of Joint Replacement Surgery.}, journal = {JB &amp; JS open access}, volume = {9}, number = {2}, pages = {}, pmid = {38638595}, issn = {2472-7245}, abstract = {BACKGROUND: The prevalence of revision surgery due to aseptic loosening and periprosthetic joint infection (PJI) following total hip and knee arthroplasty is growing. Strategies to prevent the need for revision surgery and its associated health-care costs and patient morbidity are needed. Therapies that modulate the gut microbiota to influence bone health and systemic inflammation are a novel area of research.<br><br>METHODS: A literature review of preclinical and clinical peer-reviewed articles relating to the role of the gut microbiota in bone health and PJI was performed.<br><br>RESULTS: There is evidence that the gut microbiota plays a role in maintaining bone mineral density, which can contribute to osseointegration, osteolysis, aseptic loosening, and periprosthetic fractures. Similarly, the gut microbiota influences gut permeability and the potential for bacterial translocation to the bloodstream, increasing susceptibility to PJI.<br><br>CONCLUSIONS: Emerging evidence supports the role of the gut microbiota in the development of complications such as aseptic loosening and PJI after total hip or knee arthroplasty. There is a potential for microbial therapies such as probiotics or fecal microbial transplantation to moderate the risk of developing these complications. However, further investigation is required.<br><br>CLINICAL RELEVANCE: Modulation of the gut microbiota may influence patient outcomes following total joint arthroplasty.}, }
@article {pmid38637862, year = {2024}, author = {Zhao, H and Zhou, Y and Xu, J and Zhang, Y and Wang, H and Zhao, C and Huang, H and Yang, J and Huang, C and Li, Y and Wang, L and Nie, Y}, title = {Short-chain fatty acid-producing bacterial strains attenuate experimental ulcerative colitis by promoting M2 macrophage polarization via JAK/STAT3/FOXO3 axis inactivation.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {369}, pmid = {38637862}, issn = {1479-5876}, support = {82270577//National Natural Science Foundation of China/ ; 202201020297//Guangzhou Planned Project of Science and Technology/ ; 202201020248,202002020012//Guangzhou Planned Project of Science and Technology/ ; 202102080044//Guangzhou Planned Project of Science and Technology/ ; KY17010003//Guangzhou Key Laboratory of Digestive Diseases (2022-2023)/ ; 2020A1515011000//Natural Science Foundation of Guangdong Province/ ; 2020ZYGXZR024//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Humans ; Mice ; Animals ; *Colitis, Ulcerative/therapy ; RNA, Ribosomal, 16S/genetics/metabolism ; *Gastrointestinal Microbiome ; *Colitis ; *Inflammatory Bowel Diseases ; Fatty Acids, Volatile/adverse effects/metabolism ; Bacteria/metabolism ; Disease Models, Animal ; Inflammation ; Dextran Sulfate/adverse effects ; Mice, Inbred C57BL ; Colon ; Forkhead Box Protein O3/metabolism ; *STAT3 Transcription Factor ; }, abstract = {BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms.<br><br>METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays.<br><br>RESULTS: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro.<br><br>CONCLUSIONS: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.}, }
@article {pmid38635481, year = {2024}, author = {Zambrano, LD and Newhams, MM and Simeone, RM and Payne, AB and Wu, M and Orzel-Lockwood, AO and Halasa, NB and Calixte, JM and Pannaraj, PS and Mongkolrattanothai, K and Boom, JA and Sahni, LC and Kamidani, S and Chiotos, K and Cameron, MA and Maddux, AB and Irby, K and Schuster, JE and Mack, EH and Biggs, A and Coates, BM and Michelson, KN and Bline, KE and Nofziger, RA and Crandall, H and Hobbs, CV and Gertz, SJ and Heidemann, SM and Bradford, TT and Walker, TC and Schwartz, SP and Staat, MA and Bhumbra, SS and Hume, JR and Kong, M and Stockwell, MS and Connors, TJ and Cullimore, ML and Flori, HR and Levy, ER and Cvijanovich, NZ and Zinter, MS and Maamari, M and Bowens, C and Zerr, DM and Guzman-Cottrill, JA and Gonzalez, I and Campbell, AP and Randolph, AG and , }, title = {Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron-Associated Hospitalization in Children and Adolescents - United States, 2021-2023.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {73}, number = {15}, pages = {330-338}, pmid = {38635481}, issn = {1545-861X}, mesh = {Humans ; Adolescent ; Child ; United States/epidemiology ; *COVID-19 Vaccines ; *COVID-19/epidemiology/prevention &amp; control ; mRNA Vaccines ; Vaccine Efficacy ; SARS-CoV-2 ; Hospitalization ; RNA, Messenger ; }, abstract = {Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.}, }
@article {pmid38635321, year = {2024}, author = {Wang, M and Lkhagva, E and Kim, S and Zhai, C and Islam, MM and Kim, HJ and Hong, ST}, title = {The gut microbe pair of Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270 confers complete protection against SARS-CoV-2 infection by activating CD8+ T cell-mediated immunity.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2342497}, pmid = {38635321}, issn = {1949-0984}, mesh = {Animals ; Cricetinae ; Ruminococcus ; *Gastrointestinal Microbiome ; *COVID-19 ; SARS-CoV-2 ; Clostridiales ; CD8-Positive T-Lymphocytes ; Immunity, Cellular ; }, abstract = {Despite the potential protective role of the gut microbiome against COVID-19, specific microbes conferring resistance to COVID-19 have not yet been identified. In this work, we aimed to identify and validate gut microbes at the species level that provide protection against SARS-CoV-2 infection. To identify gut microbes conferring protection against COVID-19, we conducted a fecal microbiota transplantation (FMT) from an individual with no history of COVID-19 infection or immunization into a lethal COVID-19 hamster model. FMT from this COVID-19-resistant donor resulted in significant phenotypic changes related to COVID-19 sensitivity in the hamsters. Metagenomic analysis revealed distinct differences in the gut microbiome composition among the hamster groups, leading to the identification of two previously unknown bacterial species: Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, both associated with COVID-19 resistance. Subsequently, we conducted a proof-of-concept confirmation animal experiment adhering to Koch's postulates. Oral administration of this gut microbe pair, Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, to the hamsters provided complete protection against SARS-CoV-2 infection through the activation of CD8+ T cell mediated immunity. The prophylactic efficacy of the gut microbe pair against SARS-CoV-2 infection was comparable to, or even superior to, current mRNA vaccines. This strong prophylactic efficacy suggests that the gut microbe pair could be developed as a host-directed universal vaccine for all betacoronaviruses, including potential future emerging viruses.}, }
@article {pmid38635003, year = {2024}, author = {Lee, SH and Lee, JH and Lee, SW}, title = {Application of Microbiome-Based Therapies in Chronic Respiratory Diseases.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {62}, number = {3}, pages = {201-216}, pmid = {38635003}, issn = {1976-3794}, support = {2020R1A2C1008431//National Research Foundation of Korea/ ; 2023R1A2C2006688//National Research Foundation of Korea/ ; RS-2023-00222687//National Research Foundation of Korea/ ; 2022M3A9G8017220//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/administration &amp; dosage/therapeutic use ; *Dysbiosis/therapy/microbiology ; *Fecal Microbiota Transplantation ; Lung/microbiology ; Chronic Disease ; Prebiotics/administration &amp; dosage ; Microbiota ; Animals ; Bacteria/classification/metabolism/genetics ; }, abstract = {The application of microbiome-based therapies in various areas of human disease has recently increased. In chronic respiratory disease, microbiome-based clinical applications are considered compelling options due to the limitations of current treatments. The lung microbiome is ecologically dynamic and affected by various conditions, and dysbiosis is associated with disease severity, exacerbation, and phenotype as well as with chronic respiratory disease endotype. However, it is not easy to directly modulate the lung microbiome. Additionally, studies have shown that chronic respiratory diseases can be improved by modulating gut microbiome and administrating metabolites. Although the composition, diversity, and abundance of the microbiome between the gut and lung are considerably different, modulation of the gut microbiome could improve lung dysbiosis. The gut microbiome influences that of the lung via bacterial-derived components and metabolic degradation products, including short-chain fatty acids. This phenomenon might be associated with the cross-talk between the gut microbiome and lung, called gut-lung axis. There are multiple alternatives to modulate the gut microbiome, such as prebiotics, probiotics, and postbiotics ingestion and fecal material transplantation. Several studies have shown that high-fiber diets, for example, present beneficial effects through the production of short-chain fatty acids. Additionally, genetically modified probiotics to secrete some beneficial molecules might also be utilized to treat chronic respiratory diseases. Further studies on microbial modulation to regulate immunity and potentiate conventional pharmacotherapy will improve microbiome modulation techniques, which will develop as a new therapeutic area in chronic respiratory diseases.}, }
@article {pmid38631415, year = {2024}, author = {Lee, CYQ and Margolis, KG}, title = {Unlocking the Potential of Fecal Virome Transplants: Modulating the Gut-Brain Axis in Stress-Related Disorders.}, journal = {Gastroenterology}, volume = {167}, number = {3}, pages = {625-626}, doi = {10.1053/j.gastro.2024.04.006}, pmid = {38631415}, issn = {1528-0012}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Brain-Gut Axis ; Animals ; Gastrointestinal Microbiome ; Virome ; Stress, Psychological ; Feces/virology ; Dysbiosis ; }, }
@article {pmid38631285, year = {2024}, author = {Kang, X and Lau, HC and Yu, J}, title = {Modulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy.}, journal = {Cell reports. Medicine}, volume = {5}, number = {4}, pages = {101478}, pmid = {38631285}, issn = {2666-3791}, mesh = {Humans ; *Gastrointestinal Microbiome ; Immunotherapy ; Treatment Outcome ; *Microbiota ; Fecal Microbiota Transplantation ; *Neoplasms ; }, abstract = {Immunotherapy has emerged as a robust approach against cancer, yet its efficacy has varied among individuals, accompanied by the occurrence of immune-related adverse events. As a result, the efficacy of immunotherapy is far from satisfactory, and enormous efforts have been invested to develop strategies to improve patient outcomes. The gut microbiome is now well acknowledged for its critical role in immunotherapy, with better understanding on host-microbes interaction in the context of cancer treatment. Also, an increasing number of trials have been conducted to evaluate the potential and feasibility of microbiome-targeting approaches to enhance efficacy of cancer treatment in patients. Here, the role of the gut microbiome and metabolites (e.g., short-chain fatty acids, tryptophan metabolites) in immunotherapy and the underlying mechanisms are explored. The application of microbiome-targeting approaches that aim to improve immunotherapy efficacy (e.g., fecal microbiota transplantation, probiotics, dietary intervention) is also elaborated, with further discussion on current challenges and suggestions for future research.}, }
@article {pmid38628492, year = {2024}, author = {Alghamdi, W and Mosli, M and Alqahtani, SA}, title = {Gut microbiota in MAFLD: therapeutic and diagnostic implications.}, journal = {Therapeutic advances in endocrinology and metabolism}, volume = {15}, number = {}, pages = {20420188241242937}, pmid = {38628492}, issn = {2042-0188}, abstract = {Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease, is becoming a significant contributor to chronic liver disease globally, surpassing other etiologies, such as viral hepatitis. Prevention and early treatment strategies to curb its growing prevalence are urgently required. Recent evidence suggests that targeting the gut microbiota may help treat and alleviate disease progression in patients with MAFLD. This review aims to explore the complex relationship between MAFLD and the gut microbiota in relation to disease pathogenesis. Additionally, it delves into the therapeutic strategies targeting the gut microbiota, such as diet, exercise, antibiotics, probiotics, synbiotics, glucagon-like peptide-1 receptor agonists, and fecal microbiota transplantation, and discusses novel biomarkers, such as microbiota-derived testing and liquid biopsy, for their diagnostic and staging potential. Overall, the review emphasizes the urgent need for preventive and therapeutic strategies to address the devastating consequences of MAFLD at both individual and societal levels and recognizes that further exploration of the gut microbiota may open avenues for managing MAFLD effectively in the future.}, }
@article {pmid38628273, year = {2024}, author = {Hao, L and Yu, Z and Sun, J and Li, Z and Li, J and Deng, Y and Huang, H and Huo, H and Li, H and Huang, L}, title = {Supplementation of Crataegi fructus alleviates functional dyspepsia and restores gut microbiota in mice.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1385159}, pmid = {38628273}, issn = {2296-861X}, abstract = {INTRODUCTION: Functional dyspepsia (FD), also known as non-ulcerative dyspepsia, is a common digestive system disorder.<br><br>METHODS: In this study, an FD model was established using hunger and satiety disorders combined with an intraperitoneal injection of L-arginine. Indices used to evaluate the efficacy of hawthorn in FD mice include small intestinal propulsion rate, gastric residual rate, general condition, food intake, amount of drinking water, gastric histopathological examination, and serum nitric oxide (NO) and gastrin levels. Based on the intestinal flora and their metabolites, short-chain fatty acids (SCFAs), the mechanism of action of Crataegi Fructus (hawthorn) on FD was studied. The fecal microbiota transplantation test was used to verify whether hawthorn altered the structure of the intestinal flora.<br><br>RESULTS: The results showed that hawthorn improved FD by significantly reducing the gastric residual rate, increasing the intestinal propulsion rate, the intake of food and drinking water, and the levels of gastrointestinal hormones. Simultaneously, hawthorn elevated substance P and 5-hydroxytryptamine expression in the duodenum, reduced serum NO levels, and increased vasoactive intestinal peptide expression in the duodenum. Notably, hawthorn increased the abundance of beneficial bacteria and SCFA-producing bacteria in the intestines of FD mice, decreased the abundance of conditional pathogenic bacteria, and significantly increased the SCFA content in feces.<br><br>DISCUSSION: The mechanism by which hawthorn improves FD may be related to the regulation of intestinal flora structure and the production of SCFAs.}, }
@article {pmid38626129, year = {2024}, author = {Gong, J and Zhang, Q and Hu, R and Yang, X and Fang, C and Yao, L and Lv, J and Wang, L and Shi, M and Zhang, W and Ma, S and Xiang, H and Zhang, H and Hou, DX and Yin, Y and He, J and Peng, L and Wu, S}, title = {Effects of Prevotella copri on insulin, gut microbiota and bile acids.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2340487}, pmid = {38626129}, issn = {1949-0984}, mesh = {Humans ; Child ; Animals ; Mice ; Insulin ; *Gastrointestinal Microbiome ; *Pediatric Obesity ; Bile Acids and Salts/pharmacology ; Blood Glucose ; *Diabetes Mellitus, Type 2 ; Mice, Obese ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; *Prevotella ; }, abstract = {Obesity is becoming a major global health problem in children that can cause diseases such as type 2 diabetes and metabolic disorders, which are closely related to the gut microbiota. However, the underlying mechanism remains unclear. In this study, a significant positive correlation was observed between Prevotella copri (P. copri) and obesity in children (p = 0.003). Next, the effect of P. copri on obesity was explored by using fecal microbiota transplantation (FMT) experiment. Transplantation of P. copri. increased serum levels of fasting blood glucose (p < 0.01), insulin (p < 0.01) and interleukin-1β (IL-1β) (p < 0.05) in high-fat diet (HFD)-induced obese mice, but not in normal mice. Characterization of the gut microbiota indicated that P. copri reduced the relative abundance of the Akkermansia genus in mice (p < 0.01). Further analysis on bile acids (BAs) revealed that P. copri increased the primary BAs and ursodeoxycholic acid (UDCA) in HFD-induced mice (p < 0.05). This study demonstrated for the first time that P. copri has a significant positive correlation with obesity in children, and can increase fasting blood glucose and insulin levels in HFD-fed obese mice, which are related to the abundance of Akkermansia genus and bile acids.}, }
@article {pmid38625103, year = {2024}, author = {Zhao, Z and Li, C and Huang, J and Yuan, X and Cui, Y and Liu, Y and Zhou, Y and Zhu, Z and Zhang, Z}, title = {Phlorizin Limits Bovine Viral Diarrhea Virus Infection in Mice via Regulating Gut Microbiota Composition.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {17}, pages = {9906-9914}, doi = {10.1021/acs.jafc.4c01228}, pmid = {38625103}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; Cattle ; *Bacteria/classification/isolation &amp; purification/genetics/drug effects ; *Bovine Virus Diarrhea-Mucosal Disease ; *Diarrhea Viruses, Bovine Viral/drug effects ; Antiviral Agents/pharmacology/administration &amp; dosage ; Feces/microbiology/virology ; Female ; Mice, Inbred BALB C ; Male ; }, abstract = {Phlorizin (PHZ) is one of the main pharmacologically active ingredients in Lithocarpus polystachyus. We have previously shown that PHZ inhibits the replication of bovine viral diarrhea virus (BVDV), but the exact antiviral mechanism, especially in vivo, is still unknown. Here, we further confirm that PHZ has good protective effects in BVDV-infected mice. We analyzed BVDV-induced CD3[+], CD4[+], and CD8[+] T cells among peripheral blood lymphocytes and found that PHZ significantly restored their percentage. Metagenomic analyses revealed that PHZ markedly improved the richness and diversity of intestinal microbiota and increased the abundance of potentially health-related microbes (families Lachnosipiraceae, Ruminococcaceae, and Oscillospiraceae). Specifically, the relative abundance of short chain fatty acid (SCFA)-producing bacteria, including Lachnospiraceae_UCG-006, unclassified_f_Ruminococcaceae, Oscillibacter, Intestinimonas, Blautia, and Lachnoclostridium increased significantly after PHZ treatment. Interestingly, BVDV-infected mice that received fecal microbiota from PHZ-treated mice (PHZ-FMT) had a significantly lower viral load in the duodenum and jejunum than untreated mice. Pathological lesions of duodenum and jejunum were also greatly reduced in the PHZ-FMT group, confirming a significant antiviral effect. These findings show that gut microbiota play an important role in PHZ's antiviral activity and suggest that their targeted intervention might be a promising endogenous strategy to prevent and control BVDV.}, }
@article {pmid38623584, year = {2024}, author = {Qu, B and Zhang, XE and Feng, H and Yan, B and Bai, Y and Liu, S and He, Y}, title = {Microbial perspective on the skin-gut axis and atopic dermatitis.}, journal = {Open life sciences}, volume = {19}, number = {1}, pages = {20220782}, pmid = {38623584}, issn = {2391-5412}, abstract = {Atopic dermatitis (AD) is a relapsing inflammatory skin condition that has become a global health issue with complex etiology and mounting prevalence. The association of AD with skin and gut microbiota has been revealed by virtue of the continuous development of sequencing technology and genomics analysis. Also, the gut-brain-skin axis and its mutual crosstalk mechanisms have been gradually verified. Accordingly, the microbiota-skin-gut axis also plays an important role in allergic skin inflammation. Herein, we reviewed the relationship between the microbiota-skin-gut axis and AD, explored the underlying signaling molecules and potential pathways, and focused on the potential mechanisms of probiotics, antimicrobial peptides (AMPs), coagulase-negative staphylococci transplantation, fecal microbiota transplantation, AMPs, and addition of essential fatty acids in alleviating AD, with the aim to provide a new perspective for targeting microbiota in the treatment of allergic skin inflammation.}, }
@article {pmid38622917, year = {2024}, author = {Lv, C and Cheng, L and Feng, W and Xie, H and Kou, J and Wang, L and Shi, M and Song, X and Wang, X and Chen, S and Xue, L and Zhang, C and Li, X and Zhao, H}, title = {Targeting microbiota-immune-synaptic plasticity to explore the effect of tea polyphenols on improving memory in the aged type 2 diabetic rat model.}, journal = {Nutritional neuroscience}, volume = {27}, number = {12}, pages = {1422-1438}, doi = {10.1080/1028415X.2024.2341188}, pmid = {38622917}, issn = {1476-8305}, mesh = {Animals ; *Neuronal Plasticity/drug effects ; *Diabetes Mellitus, Type 2 ; *Gastrointestinal Microbiome/drug effects ; Male ; *Diabetes Mellitus, Experimental ; Rats ; *Polyphenols/pharmacology/administration &amp; dosage ; *Memory/drug effects ; *Hippocampus/drug effects/metabolism ; Tea/chemistry ; Rats, Sprague-Dawley ; Memory Disorders/prevention &amp; control ; Fecal Microbiota Transplantation ; Disease Models, Animal ; }, abstract = {OBJECTIVES: The study aimed to explore whether TP could improve memory in the aged type 2 diabetic rat model by regulating microbiota-immune-synaptic plasticity axis.<br><br>METHODS: The experiment was divided into two parts. Firstly, to investigate the effects of TP on the physiopathology of the aged T2DM model rats, rats were randomly divided into the Normal control group, the aged group, the Aged T2DM model group, the TP 75, 150, 300 mg/kg groups, the 150 mg/kg Piracetam group and the 3 mg/kg Rosiglitazone group. Then, to further verify whether TP improved memory in aged T2DM rat model by regulating intestinal flora, the fecal microbiota transplantation (FMT) from the rats in the 300 mg/kg TP group into the rats in the aged T2DM model group was carried out. Effects on gut microbiota, colonic integrity (epithelial tight junction proteins), and endotoxemia (serum LPS) were examined, along with synaptic structure, synaptic plasticity-related structural proteins and inflammation signaling of the hippocampus in our study.<br><br>RESULTS: Our results demonstrated that TP alleviated memory impairments in the aged T2DM rat model. The specific outcomes were as follows: TP 300 mg/kg corrected the gut dysbacteriosis, alleviated intestinal permeability reduction and peripheral/central inflammation, inhibited the TLR4/NF-&#x3ba;B signaling pathway. Meanwhile, TP improved the synaptic plasticity in the hippocampus of the aged T2DM model rats, whose expressions of SYN, PSD 95, NMDAR1 and GluR1 in hippocampus were significantly up-regulated. Surprisingly, rats of the FMT group displayed the same changes.<br><br>DISCUSSION: TP improves the memory in aged T2DM rat model. The mechanism may be related to the alteration of gut flora, which can inhibit hippocampal TLR4/NF-&#x3ba;B signaling to attenuate neuroinflammation, then improve synaptic plasticity. The study proposes that TP interventions aimed at manipulating the gut microbiota may hold great potential as an effective approach for preventing and treating this disease.}, }
@article {pmid38622523, year = {2024}, author = {You, X and Qiu, J and Li, Q and Zhang, Q and Sheng, W and Cao, Y and Fu, W}, title = {Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {472}, pmid = {38622523}, issn = {1471-2407}, support = {82104853//National Natural Science Foundation of China/ ; BAZYY20220703//Shenzhen Bao'an Chinese Medicine Hospital Research Program/ ; 2023-QNRC2-A10//Young Elite Scientists Sponsorship Program by CACM/ ; 2024A1515012209//Project of Guangdong Provincial Department of Science and Technology/ ; 2021JD082//Bao'an District Science and Technology Innovation Bureau Research Program/ ; }, mesh = {Male ; Humans ; Animals ; Mice ; Mice, Nude ; Receptor for Advanced Glycation End Products ; *Gastrointestinal Microbiome ; *Liver Neoplasms ; *Prostatic Neoplasms/drug therapy ; Homeostasis ; *Saponins ; *Triterpenes ; }, abstract = {BACKGROUND: Prostate cancer (PCa) is becoming the most common malignancy in men worldwide. We investigated the effect of astragaloside IV combined with PESV on the gut microbiota and metabolite of PCa mice and the process of treating PCa.<br><br>METHODS: Nude mice were genetically modified to develop tumors characteristic of PCa. The treatment of PCa mice involved the administration of a combination of astragaloside IV and peptides derived from scorpion venom (PESV). Feces were collected for both 16&#xa0;S rDNA and metabolic analysis. Fecal supernatant was extracted and used for fecal transplantation in PCa mice. Tumor development was observed in both PCa mice and nude mice. Tumor histopathology was examined, and the expression of inflammatory factors and the AGE-RAGE axis in PCa tissues were analyzed.<br><br>RESULTS: PCa mice treated with Astragaloside IV in combination with PESV showed a significant reduction in tumor volume and weight, and stabilization of gut microbiota and metabolites. At the Genus level, significant differences were observed in Porphyromonas, Corynebacterium, Arthromitus and Blautia, and the differential metabolites were PA16_016_0, Astragaloside+, Vitamin A acid, Nardosinone, a-Nortestoster, D-Pantethine, Hypoxanthine, Pregnenolone, cinnamic acid, Pyridoxa, Cirtruline and Xanthurenate. There was a correlation between gut microbiota and metabolites. After the fecal transplantation, tumor growth was effectively suppressed in the PCa mice. Notably, both the mRNA and protein levels of the receptor for advanced glycation end products (RAGE) were significantly decreased. Furthermore, the expression of inflammatory factors, namely NF-&#x3ba;B, TNF-&#x3b1;, and IL-6, in the tumor tissues was significantly attenuated. Conversely, upregulation of RAGE led to increased inflammation and reversed tumor growth in the mice.<br><br>CONCLUSION: Astragaloside IV combined with PESV could treat PCa by intervening in gut microbiota composition and metabolite by targeting RAGE.}, }
@article {pmid38621910, year = {2024}, author = {Yu, HC and Meng, YY and Wang, EK and Yuan, JY and Peng, Y and Li, XB}, title = {[Buzhong Yiqi Decoction ameliorates spleen deficiency syndrome by regulating gut microbiota].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {49}, number = {4}, pages = {1028-1043}, doi = {10.19540/j.cnki.cjcmm.20231013.701}, pmid = {38621910}, issn = {1001-5302}, mesh = {Humans ; Mice ; Animals ; *Spleen ; Tumor Necrosis Factor-alpha/pharmacology ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Interleukin-2/pharmacology ; Serotonin ; Immunoglobulin A/pharmacology ; }, abstract = {This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1β, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1β, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500＿29＿marine＿group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1β level had a significantly positive correlation with Acinetobacter and CL500＿29＿marine＿group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.}, }
@article {pmid38617735, year = {2024}, author = {Wang, MY and Sang, LX and Sun, SY}, title = {Gut microbiota and female health.}, journal = {World journal of gastroenterology}, volume = {30}, number = {12}, pages = {1655-1662}, pmid = {38617735}, issn = {2219-2840}, mesh = {Female ; Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; *Breast Neoplasms ; *Endometriosis ; Estrogens ; }, abstract = {The gut microbiota is recognized as an endocrine organ with the capacity to influence distant organs and associated biological pathways. Recent advancements underscore the critical role of gut microbial homeostasis in female health; with dysbiosis potentially leading to diseases among women such as polycystic ovarian syndrome, endometriosis, breast cancer, cervical cancer, and ovarian cancer etc. Despite this, there has been limited discussion on the underlying mechanisms. This editorial explores the three potential mechanisms through which gut microbiota dysbiosis may impact the development of diseases among women, namely, the immune system, the gut microbiota-estrogen axis, and the metabolite pathway. We focused on approaches for treating diseases in women by addressing gut microbiota imbalances through probiotics, prebiotics supplementation, and fecal microbiota transplantation (FMT). Future studies should focus on determining the molecular mechanisms underlying associations between dysbiosis of gut microbiota and female diseases to realize precision medicine, with FMT emerging as a promising intervention.}, }
@article {pmid38617537, year = {2024}, author = {Yu, X and Li, W and Li, Z and Wu, Q and Sun, S}, title = {Influence of Microbiota on Tumor Immunotherapy.}, journal = {International journal of biological sciences}, volume = {20}, number = {6}, pages = {2264-2294}, pmid = {38617537}, issn = {1449-2288}, mesh = {Humans ; Immunotherapy ; *Microbiota ; *Probiotics/therapeutic use ; *Neoplasms/therapy ; }, abstract = {The role of the microbiome in immunotherapy has recently garnered substantial attention, with molecular studies and clinical trials providing emerging evidence on the pivotal influence of the microbiota in enhancing therapeutic outcomes via immune response modulation. However, the impact of microbial communities can considerably vary across individuals and different immunotherapeutic approaches, posing prominent challenges in harnessing their potential. In this comprehensive review, we outline the current research applications in tumor immunotherapy and delve into the possible mechanisms through which immune function is influenced by microbial communities in various body sites, encompassing those in the gut, extraintestinal barrier, and intratumoral environment. Furthermore, we discuss the effects of diverse microbiome-based strategies, including probiotics, prebiotics, fecal microbiota transplantation, and the targeted modulation of specific microbial taxa, and antibiotic treatments on cancer immunotherapy. All these strategies potentially have a profound impact on immunotherapy and pave the way for personalized therapeutic approaches and predictive biomarkers.}, }
@article {pmid38617453, year = {2024}, author = {Chen, SJ and Zhang, DY and Wu, X and Zhang, FM and Cui, BT and Huang, YH and Zhang, ZL and Wang, R and Bai, FH}, title = {Washed microbiota transplantation for Crohn's disease: A metagenomic, metatranscriptomic, and metabolomic-based study.}, journal = {World journal of gastroenterology}, volume = {30}, number = {11}, pages = {1572-1587}, pmid = {38617453}, issn = {2219-2840}, mesh = {Humans ; Amino Acids ; *Antifibrinolytic Agents ; *Crohn Disease/diagnosis/therapy ; Escherichia coli ; Metagenome ; *Microbiota ; Prospective Studies ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported.<br><br>AIM: To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT.<br><br>METHODS: We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure.<br><br>RESULTS: Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT.<br><br>CONCLUSION: WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.}, }
@article {pmid38617293, year = {2024}, author = {Joldrichsen, MR and Kim, E and Steiner, HE and Jeong, YJ and Premanandan, C and Hsueh, W and Ziouzenkova, O and Cormet-Boyaka, E and Boyaka, PN}, title = {Loss of Paneth cells dysregulates gut ILC subsets and enhances weight gain response to high fat diet in a mouse model.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.29.587349}, pmid = {38617293}, issn = {2692-8205}, abstract = {Obesity has been associated with dysbiosis, but innate mechanisms linking intestinal epithelial cell subsets and obesity remain poorly understood. Using mice lacking Paneth cells (Sox9 [ΔIEC] mice), small intestinal epithelial cells specialized in the production of antimicrobial products and cytokines, we show that dysbiosis alone does not induce obesity or metabolic disorders. Loss of Paneth cells reduced ILC3 and increased ILC2 numbers in the intestinal lamina propria. High-fat diet (HFD) induced higher weight gain and more severe metabolic disorders in Sox9 [ΔIEC] mice. Further, HFD enhances the number of ILC1 in the intestinal lamina propria of Sox9 [ΔIEC] mice and increases intestinal permeability and the accumulation of immune cells (inflammatory macrophages and T cells, and B cells) in abdominal fat tissues of obese Sox9 [ΔIEC] . Transplantation of fecal materials from Sox9 [ΔIEC] mice in germ-free mice before HFD further confirmed the regulatory role of Paneth cells for gut ILC subsets and the development of obesity.}, }
@article {pmid38616586, year = {2024}, author = {Joshi, B and Yadav, SK and Shakya Hada, MS and Shrestha, S and Shrestha, KK and Shrestha, PC and Awal, BK}, title = {Post-Transplant Fecal Carriage of Antibiotic Resistant and B-Lactamases-Producing Enterobacteriales among Renal Transplant Recipients.}, journal = {Journal of Nepal Health Research Council}, volume = {21}, number = {4}, pages = {578-586}, doi = {10.33314/jnhrc.v21i4.4801}, pmid = {38616586}, issn = {1999-6217}, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Ceftazidime ; Transplant Recipients ; *Kidney Transplantation ; Escherichia coli ; Nepal ; beta-Lactamases ; Klebsiella ; }, abstract = {BACKGROUND: The intestinal colonization and transmission of antibiotic-resistant Enterobacteriales to renal transplant recipients may pose a threat to them because they are profoundly immunocompromised and vulnerable to infection. Hence, it is crucial to identify these antibiotic-resistant fecal Enterobacteriales harboring high-risk populations. The objective of this study was to determine antibiotic resistance as well as β-lactamases production in fecal Enterobacteriales among renal transplant recipients.<br><br>METHODS: The stool samples, one collected from each transplant recipient, were processed for isolation and identification of Enterobacteriales and were tested for their antibiotic susceptibility, extended-spectrum &#x3b2;-lactamase, and metallo-&#x3b2;-lactamase production by standard methods.<br><br>RESULTS: A total of 103 Enterobacteriales comprising of Escherichia coli (86.4%), Klebsiella species (11.7%), and Citrobacter species (1.9%) were isolated and more than 60% of the E. coli were found resistant to ceftazidime and ciprofloxacin and around half of the Klebsiella species were resistant to ceftazidime and fluroquinolones. The&#xa0;extended-spectrum &#x3b2;-lactamase production was seen in 3.4% and 8.3% and metallo-&#x3b2;-lactamase production in 24.7% and 33.3% of E. coli and Klebsiella species, respectively. The high proportion of &#x3b2;-lactamase-producers were resistant to piperacillin-tazobactam, meropenem, gentamicin, and amikacin than &#x3b2;-lactamases non-producers.<br><br>CONCLUSION: Since the antibiotic resistance is higher in fecal Enterobacteriales, each&#xa0;renal transplant recipient should be screened for these highly resistant intestinal colonizers after transplantation in order to prevent infections and to&#xa0;reduce the rate of transplant failure due to infections.}, }
@article {pmid38613431, year = {2024}, author = {Lee, MA and Questa, M and Wanakumjorn, P and Kol, A and McLaughlin, B and Weimer, BC and Buono, A and Suchodolski, JS and Marsilio, S}, title = {Safety profile and effects on the peripheral immune response of fecal microbiota transplantation in clinically healthy dogs.}, journal = {Journal of veterinary internal medicine}, volume = {38}, number = {3}, pages = {1425-1436}, pmid = {38613431}, issn = {1939-1676}, support = {P30 CA093373/CA/NCI NIH HHS/United States ; S10 RR026825/RR/NCRR NIH HHS/United States ; //2022 Comparative Gastroenterology Society (CGS)/IDEXX Veterinary Student Summer Scholar Award/ ; NCI P30 CA093373 (Comprehensive Cancer Center), S10 OD018223 (Astrios Cell Sorter), S10 RR 026825 (Fortessa Cytometer)//University of California Davis Flow Cytometry Shared Resource Laboratory/ ; S10 OD018223/OD/NIH HHS/United States ; }, mesh = {Animals ; Dogs ; *Fecal Microbiota Transplantation/veterinary/adverse effects ; Female ; Male ; Feces/microbiology ; Prospective Studies ; Cytokines/blood/metabolism ; Dysbiosis/veterinary/therapy ; Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used for gastrointestinal and extra-gastrointestinal diseases in veterinary medicine. However, its effects on immune responses and possible adverse events have not been systematically investigated.<br><br>HYPOTHESIS/OBJECTIVES: Determine the short-term safety profile and changes in the peripheral immune system after a single FMT administration in healthy dogs.<br><br>ANIMALS: Ten client-owned, clinically healthy dogs as FMT recipients, and 2 client-owned clinically healthy dogs as FMT donors.<br><br>METHODS: Prospective non-randomized clinical trial. A single rectal enema of 5&#x2009;g/kg was given to clinically healthy canine recipients. During the 28&#x2009;days after FMT administration, owners self-reported adverse events and fecal scores. On Days 0 (baseline), 1, 4, 10, and 28 after FMT, fecal and blood samples were collected. The canine fecal dysbiosis index (DI) was calculated using qPCR.<br><br>RESULTS: No significant changes were found in the following variables: CBC, serum biochemistry, C-reactive protein, serum cytokines (interleukins [IL]-2, -6, -8, tumor necrosis factor [TNF]-&#x3b1;), peripheral leukocytes (B cells, T cells, cluster of differentiation [CD]4+ T cells, CD8+ T cells, T regulatory cells), and the canine DI. Mild vomiting (n&#x2009;=&#x2009;3), diarrhea (n&#x2009;=&#x2009;4), decreased activity (n&#x2009;=&#x2009;2), and inappetence (n&#x2009;=&#x2009;1) were reported, and resolved without intervention.<br><br>Fecal microbiota transplantation did not significantly alter the evaluated variables and recipients experienced minimal adverse events associated with FMT administration. Fecal microbiota transplantation was not associated with serious adverse events, changes in peripheral immunologic variables, or the canine DI in the short-term.}, }
@article {pmid38613119, year = {2024}, author = {Zhou, Y and Zeng, Y and Wang, R and Pang, J and Wang, X and Pan, Z and Jin, Y and Chen, Y and Yang, Y and Ling, W}, title = {Resveratrol Improves Hyperuricemia and Ameliorates Renal Injury by Modulating the Gut Microbiota.}, journal = {Nutrients}, volume = {16}, number = {7}, pages = {}, pmid = {38613119}, issn = {2072-6643}, support = {81730090//National Natural Science Foundation of China/ ; 81973022//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Hyperuricemia/drug therapy ; *Gastrointestinal Microbiome ; Resveratrol/pharmacology ; Uric Acid ; Kidney Tubules ; Inflammation ; }, abstract = {Resveratrol (RES) has been reported to prevent hyperuricemia (HUA); however, its effect on intestinal uric acid metabolism remains unclear. This study evaluated the impact of RES on intestinal uric acid metabolism in mice with HUA induced by a high-fat diet (HFD). Moreover, we revealed the underlying mechanism through metagenomics, fecal microbiota transplantation (FMT), and 16S ribosomal RNA analysis. We demonstrated that RES reduced the serum uric acid, creatinine, urea nitrogen, and urinary protein levels, and improved the glomerular atrophy, unclear renal tubule structure, fibrosis, and renal inflammation. The results also showed that RES increased intestinal uric acid degradation. RES significantly changed the intestinal flora composition of HFD-fed mice by enriching the beneficial bacteria that degrade uric acid, reducing harmful bacteria that promote inflammation, and improving microbial function via the upregulation of purine metabolism. The FMT results further showed that the intestinal microbiota is essential for the effect of RES on HUA, and that Lactobacillus may play a key role in this process. The present study demonstrated that RES alleviates HFD-induced HUA and renal injury by regulating the gut microbiota composition and the metabolism of uric acid.}, }
@article {pmid38613109, year = {2024}, author = {Byerley, LO and Lorenzen, B and Chang, HM and Hartman, WG and Keenan, MJ and Page, R and Luo, M and Dowd, SE and Taylor, CM}, title = {Gut Microbial Dysbiosis Differs in Two Distinct Cachectic Tumor-Bearing Models Consuming the Same Diet.}, journal = {Nutrients}, volume = {16}, number = {7}, pages = {}, pmid = {38613109}, issn = {2072-6643}, support = {P20 GM103424/GM/NIGMS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; }, mesh = {Male ; Animals ; Rats ; Cachexia/etiology ; Dysbiosis ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Diet ; *Sarcoma ; *Juglans ; }, abstract = {The impact of cancer cachexia on the colonic microbiota is poorly characterized. This study assessed the effect of two cachectic-producing tumor types on the gut microbiota to determine if a similar dysbiosis could be found. In addition, it was determined if a diet containing an immunonutrient-rich food (walnuts) known to promote the growth of probiotic bacteria in the colon could alter the dysbiosis and slow cachexia. Male Fisher 344 rats were randomly assigned to a semi-purified diet with or without walnuts. Then, within each diet group, rats were further assigned randomly to a treatment group: tumor-bearing ad libitum fed (TB), non-tumor-bearing ad libitum fed (NTB-AL), and non-tumor-bearing group pair-fed to the TB (NTB-PF). The TB group was implanted either with the Ward colon carcinoma or MCA-induced sarcoma, both transplantable tumor lines. Fecal samples were collected after the development of cachexia, and bacteria species were identified using 16S rRNA gene analysis. Both TB groups developed cachexia but had a differently altered gut microbiome. Beta diversity was unaffected by treatment (NTB-AL, TB, and NTB-PF) regardless of tumor type but was affected by diet. Also, diet consistently changed the relative abundance of several bacteria taxa, while treatment and tumor type did not. The control diet increased the abundance of A. Anaeroplasma, while the walnut diet increased the genus Ruminococcus. There were no common fecal bacterial changes characteristic of cachexia found. Diet consistently changed the gut microbiota, but these changes were insufficient to slow the progression of cachexia, suggesting cancer cachexia is more complex than a few gut microbiota shifts.}, }
@article {pmid38613058, year = {2024}, author = {Lombardi, M and Troisi, J and Motta, BM and Torre, P and Masarone, M and Persico, M}, title = {Gut-Liver Axis Dysregulation in Portal Hypertension: Emerging Frontiers.}, journal = {Nutrients}, volume = {16}, number = {7}, pages = {}, pmid = {38613058}, issn = {2072-6643}, mesh = {Humans ; *Hypertension, Portal/metabolism/physiopathology/etiology ; *Gastrointestinal Microbiome/physiology ; *Liver/metabolism ; *Dysbiosis ; Bacterial Translocation ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Portal hypertension (PH) is a complex clinical challenge with severe complications, including variceal bleeding, ascites, hepatic encephalopathy, and hepatorenal syndrome. The gut microbiota (GM) and its interconnectedness with human health have emerged as a captivating field of research. This review explores the intricate connections between the gut and the liver, aiming to elucidate how alterations in GM, intestinal barrier function, and gut-derived molecules impact the development and progression of PH. A systematic literature search, following PRISMA guidelines, identified 12 original articles that suggest a relationship between GM, the gut-liver axis, and PH. Mechanisms such as dysbiosis, bacterial translocation, altered microbial structure, and inflammation appear to orchestrate this relationship. One notable study highlights the pivotal role of the farnesoid X receptor axis in regulating the interplay between the gut and liver and proposes it as a promising therapeutic target. Fecal transplantation experiments further emphasize the pathogenic significance of the GM in modulating liver maladies, including PH. Recent advancements in metagenomics and metabolomics have expanded our understanding of the GM's role in human ailments. The review suggests that addressing the unmet need of identifying gut-liver axis-related metabolic and molecular pathways holds potential for elucidating pathogenesis and directing novel therapeutic interventions.}, }
@article {pmid38609760, year = {2024}, author = {Mullish, BH and Merrick, B and Quraishi, MN and Bak, A and Green, CA and Moore, DJ and Porter, RJ and Elumogo, NT and Segal, JP and Sharma, N and Marsh, B and Kontkowski, G and Manzoor, SE and Hart, AL and Settle, C and Keller, JJ and Hawkey, P and Iqbal, TH and Goldenberg, SD and Williams, HRT}, title = {The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.}, journal = {The Journal of hospital infection}, volume = {148}, number = {}, pages = {189-219}, doi = {10.1016/j.jhin.2024.03.001}, pmid = {38609760}, issn = {1532-2939}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Clostridium Infections/therapy ; United Kingdom ; Clostridioides difficile ; COVID-19/therapy ; Recurrence ; Gastroenterology/standards/methods ; SARS-CoV-2 ; Societies, Medical ; }, abstract = {The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.}, }
@article {pmid38609165, year = {2024}, author = {Mullish, BH and Merrick, B and Quraishi, MN and Bak, A and Green, CA and Moore, DJ and Porter, RJ and Elumogo, NT and Segal, JP and Sharma, N and Marsh, B and Kontkowski, G and Manzoor, SE and Hart, AL and Settle, C and Keller, JJ and Hawkey, P and Iqbal, TH and Goldenberg, SD and Williams, HRT}, title = {The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.}, journal = {Gut}, volume = {73}, number = {7}, pages = {1052-1075}, doi = {10.1136/gutjnl-2023-331550}, pmid = {38609165}, issn = {1468-3288}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Clostridium Infections/therapy ; *Gastroenterology/standards ; COVID-19/therapy ; SARS-CoV-2 ; Recurrence ; Clostridioides difficile ; United Kingdom ; Societies, Medical ; }, abstract = {The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.}, }
@article {pmid38608743, year = {2024}, author = {Yang, X and Zhou, Y and Tan, S and Tian, X and Meng, X and Li, Y and Zhou, B and Zhao, G and Ge, X and He, C and Cheng, W and Zhang, Y and Zheng, K and Yin, K and Yu, Y and Pan, W}, title = {Alterations in gut microbiota contribute to cognitive deficits induced by chronic infection of Toxoplasma gondii.}, journal = {Brain, behavior, and immunity}, volume = {119}, number = {}, pages = {394-407}, doi = {10.1016/j.bbi.2024.04.008}, pmid = {38608743}, issn = {1090-2139}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Cognitive Dysfunction/metabolism/etiology/microbiology ; *Toxoplasma ; *Toxoplasmosis/metabolism/complications ; *Dysbiosis/metabolism ; Humans ; Male ; *Hippocampus/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation/methods ; Butyrates/metabolism ; Female ; Cognition/physiology ; }, abstract = {Chronic infection with Toxoplasma gondii (T. gondii) emerges as a risk factor for neurodegenerative diseases in animals and humans. However, the underlying mechanisms are largely unknown. We aimed to investigate whether gut microbiota and its metabolites play a role in T. gondii-induced cognitive deficits. We found that T. gondii infection induced cognitive deficits in mice, which was characterized by synaptic ultrastructure impairment and neuroinflammation in the hippocampus. Moreover, the infection led to gut microbiota dysbiosis, barrier integrity impairment, and inflammation in the colon. Interestingly, broad-spectrum antibiotic ablation of gut microbiota attenuated the adverse effects of the parasitic infection on the cognitive function in mice; cognitive deficits and hippocampal pathological changes were transferred from the infected mice to control mice by fecal microbiota transplantation. In addition, the abundance of butyrate-producing bacteria and the production of serum butyrate were decreased in infected mice. Interestingly, dietary supplementation of butyrate ameliorated T. gondii-induced cognitive impairment in mice. Notably, compared to the healthy controls, decreased butyrate production was observed in the serum of human subjects with high levels of anti-T. gondii IgG. Overall, this study demonstrates that gut microbiota is a key regulator of T. gondii-induced cognitive impairment.}, }
@article {pmid38608488, year = {2024}, author = {Bai, X and Deng, J and Duan, Z and Fu, R and Zhu, C and Fan, D}, title = {Ginsenoside Rh4 alleviates gastrointestinal mucositis and enhances chemotherapy efficacy through modulating gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {128}, number = {}, pages = {155577}, doi = {10.1016/j.phymed.2024.155577}, pmid = {38608488}, issn = {1618-095X}, mesh = {*Ginsenosides/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Animals ; *Irinotecan/pharmacology ; *Mucositis/chemically induced/drug therapy ; Mice ; Cell Line, Tumor ; Mice, Inbred BALB C ; Fecal Microbiota Transplantation ; Xenograft Model Antitumor Assays ; Male ; Antineoplastic Agents, Phytogenic/pharmacology ; }, abstract = {BACKGROUND: Gastrointestinal mucositis stands as one of the most severe side effects of irinotecan (CPT-11). however, only palliative treatment is available at present. Therefore, there is an urgent need for adjunctive medications to alleviate the side effects of CPT-11.<br><br>PURPOSE: In this study, our objective was to explore whether ginsenoside Rh4 could serve as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, thereby alleviating the side effects of CPT-11 and augmenting its anti-tumor efficacy.<br><br>STUDY DESIGN: A CPT-11-induced gastrointestinal mucositis model was used to investigate whether ginsenoside Rh4 alleviated CPT-11-induced gastrointestinal mucositis and enhanced the anti-tumor activity of CPT-11.<br><br>METHODS: In this study, we utilized CT26 cells to establish a xenograft tumor model, employing transcriptomics, genomics, and metabolomics techniques to investigate the impact of ginsenoside Rh4 on CPT-11-induced gastrointestinal mucositis and the effect on the anti-tumor activity of CPT-11. Furthermore, we explored the pivotal role of gut microbiota and their metabolites through fecal microbiota transplantation (FMT) experiments and supplementation of the key differential metabolite, hyodeoxycholic acid (HDCA).<br><br>RESULTS: The results showed that ginsenoside Rh4 repaired the impairment of intestinal barrier function and restored intestinal mucosal homeostasis in a gut microbiota-dependent manner. Ginsenoside Rh4 treatment modulated gut microbiota diversity and upregulated the abundance of beneficial bacteria, especially Lactobacillus_reuteri and Akkermansia_muciniphila, which further regulated bile acid biosynthesis, significantly promoted the production of the beneficial secondary bile acid hyodeoxycholic acid (HDCA), thereby alleviating CPT-11-induced gut microbiota dysbiosis. Subsequently, ginsenoside Rh4 further alleviated gastrointestinal mucositis through the TGR5-TLR4-NF-&#x3ba;B signaling pathway. On the other hand, ginsenoside Rh4 combination therapy could further reduce the weight and volume of colon tumors, promote tumor cell apoptosis, and enhance the anti-tumor activity of CPT-11 by inhibiting the PI3K-Akt signaling pathway, thus exerting a synergistic anti-tumor effect.<br><br>CONCLUSION: In summary, our findings confirm that ginsenoside Rh4 can alleviate CPT-11-induced gastrointestinal mucositis and enhance the anti-tumor activity of CPT-11 by modulating gut microbiota and its related metabolites. Our study validates the potential of ginsenoside Rh4 as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, offering new therapeutic strategies for addressing chemotherapy side effects and improving chemotherapy efficacy.}, }
@article {pmid38608440, year = {2024}, author = {Zhang, W and Ling, J and Xu, B and Wang, J and Chen, Z and Li, G}, title = {Gut microbiome-mediated monocytes promote liver metastasis.}, journal = {International immunopharmacology}, volume = {133}, number = {}, pages = {111877}, doi = {10.1016/j.intimp.2024.111877}, pmid = {38608440}, issn = {1878-1705}, mesh = {*Gastrointestinal Microbiome/immunology ; Animals ; Humans ; *Liver Neoplasms/secondary/immunology ; *Monocytes/immunology ; *Fecal Microbiota Transplantation ; *Chemokine CCL2/metabolism ; Mice ; *Receptors, CCR2/metabolism ; *Toll-Like Receptor 4/metabolism ; Male ; Lipopolysaccharides/immunology ; Mice, Inbred C57BL ; Female ; Signal Transduction ; Cell Line, Tumor ; Liver/pathology/immunology/metabolism ; }, abstract = {The gut microbiome plays an important role in tumor growth by regulating immune cell function. However, the role of the gut microbiome-mediated monocytes in liver metastasis remains unclear. In this study, we found that fecal microbiome transplantation (FMT) from the stool of patients with liver metastasis (LM) significantly promoted liver metastasis compared with healthy donors (HD). Monocytes were upregulated in liver tissues by the CCL2/CCR2 axis in LM patients' stool transplanted mouse model. CCL2/CCR2 inhibition and monocyte depletion significantly suppress liver metastasis. FMT using LM patients' stool enhanced the plasma lipopolysaccharides (LPS) concentration. The LPS/TLR4 signaling pathway is crucial for gut microbiome-mediated liver metastasis. These results indicated that monocytes contribute to liver metastasis via the CCL2/CCR2 axis.}, }
@article {pmid38604201, year = {2024}, author = {Bethlehem, L and Estevinho, MM and Grinspan, A and Magro, F and Faith, JJ and Colombel, JF}, title = {Microbiota therapeutics for inflammatory bowel disease: the way forward.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {9}, number = {5}, pages = {476-486}, doi = {10.1016/S2468-1253(23)00441-7}, pmid = {38604201}, issn = {2468-1253}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy ; *Colitis, Ulcerative/therapy ; *Microbiota ; }, abstract = {Microbiota therapeutics that transplant faecal material from healthy donors to people with mild-to-moderate ulcerative colitis have shown the potential to induce remission in about 30% of participants in small, phase 2 clinical trials. Despite this substantial achievement, the field needs to leverage the insights gained from these trials and progress towards phase 3 clinical trials and drug approval, while identifying the distinct clinical niche for this new therapeutic modality within inflammatory bowel disease (IBD) therapeutics. We describe the lessons that can be learned from past studies of microbiota therapeutics, from full spectrum donor stool to defined products manufactured in vitro. We explore the actionable insights these lessons provide on the design of near-term studies and future trajectories for the integration of microbiota therapeutics in the treatment of IBD. If successful, microbiota therapeutics will provide a powerful orthogonal approach (complementing or in combination with existing immunomodulatory drugs) to raise the therapeutic ceiling for the many non-responders and partial responders within the IBD patient population.}, }
@article {pmid38604200, year = {2024}, author = {Porcari, S and Fusco, W and Spivak, I and Fiorani, M and Gasbarrini, A and Elinav, E and Cammarota, G and Ianiro, G}, title = {Fine-tuning the gut ecosystem: the current landscape and outlook of artificial microbiome therapeutics.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {9}, number = {5}, pages = {460-475}, doi = {10.1016/S2468-1253(23)00357-6}, pmid = {38604200}, issn = {2468-1253}, mesh = {Humans ; *Microbiota ; *Probiotics/therapeutic use ; Prebiotics ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiome is acknowledged as a key determinant of human health, and technological progress in the past two decades has enabled the deciphering of its composition and functions and its role in human disorders. Therefore, manipulation of the gut microbiome has emerged as a promising therapeutic option for communicable and non-communicable disorders. Full exploitation of current therapeutic microbiome modulators (including probiotics, prebiotics, and faecal microbiota transplantation) is hindered by several factors, including poor precision, regulatory and safety issues, and the impossibility of providing reproducible and targeted treatments. Artificial microbiota therapeutics (which include a wide range of products, such as microbiota consortia, bacteriophages, bacterial metabolites, and engineered probiotics) have appeared as an evolution of current microbiota modulators, as they promise safe and reproducible effects, with variable levels of precision via different pathways. We describe the landscape of artificial microbiome therapeutics, from those already on the market to those still in the pipeline, and outline the major challenges for positioning these therapeutics in clinical practice.}, }
@article {pmid38599497, year = {2024}, author = {Xu, Q and Sun, L and Chen, Q and Jiao, C and Wang, Y and Li, H and Xie, J and Zhu, F and Wang, J and Zhang, W and Xie, L and Wu, H and Zuo, Z and Chen, X}, title = {Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model.}, journal = {Brain, behavior, and immunity}, volume = {119}, number = {}, pages = {220-235}, doi = {10.1016/j.bbi.2024.04.002}, pmid = {38599497}, issn = {1090-2139}, mesh = {Animals ; Female ; *Dysbiosis/metabolism ; *Hippocampus/metabolism ; Mice ; *Gastrointestinal Microbiome/physiology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Disease Models, Animal ; *Fecal Microbiota Transplantation/methods ; *Depression, Postpartum/metabolism ; Mice, Inbred C57BL ; Depression/metabolism ; Neuroinflammatory Diseases/metabolism ; Behavior, Animal/physiology ; Anxiety/metabolism ; Brain-Gut Axis/physiology ; Inflammation/metabolism ; Ovariectomy ; }, abstract = {Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.}, }
@article {pmid38599474, year = {2024}, author = {Wang, H and Zhou, L and Zheng, Q and Song, Y and Huang, W and Yang, L and Xiong, Y and Cai, Z and Chen, Y and Yuan, J}, title = {Kai-xin-san improves cognitive impairment in D-gal and Aβ25-35 induced ad rats by regulating gut microbiota and reducing neuronal damage.}, journal = {Journal of ethnopharmacology}, volume = {329}, number = {}, pages = {118161}, doi = {10.1016/j.jep.2024.118161}, pmid = {38599474}, issn = {1872-7573}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology ; Male ; *Cognitive Dysfunction/drug therapy/chemically induced ; *Peptide Fragments ; *Amyloid beta-Peptides/metabolism ; *Alzheimer Disease/drug therapy/chemically induced ; Rats ; *Neurons/drug effects ; *Rats, Sprague-Dawley ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Hippocampus/drug effects/metabolism/pathology ; Morris Water Maze Test/drug effects ; }, abstract = {Kai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood.<br><br>AIM OF THE STUDY: To verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota.<br><br>MATERIALS AND METHODS: AD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of A&#x3b2;25-35. The pharmacodynamics of KXS in vivo includes general behavior, Morris water maze test, ELISA, Nissl &amp; HE staining and immunofluorescence. Systematic analysis of gut microbiota was conducted using 16S rRNA gene sequencing technology. The potential role of gut microbiota in the anti-AD effect of KXS was validated with fecal microbiota transplantation (FMT) experiments.<br><br>RESULTS: KXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant.<br><br>CONCLUSION: KXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.}, }
@article {pmid38599367, year = {2024}, author = {Svačina, MKR and Gao, T and Sprenger-Svačina, A and Lin, J and Ganesh, BP and Lee, J and McCullough, LD and Sheikh, KA and Zhang, G}, title = {Rejuvenating fecal microbiota transplant enhances peripheral nerve repair in aged mice by modulating endoneurial inflammation.}, journal = {Experimental neurology}, volume = {376}, number = {}, pages = {114774}, doi = {10.1016/j.expneurol.2024.114774}, pmid = {38599367}, issn = {1090-2430}, mesh = {Animals ; Mice ; *Mice, Inbred C57BL ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; *Nerve Regeneration/physiology ; *Aging ; Male ; Peripheral Nerve Injuries/therapy ; Inflammation/metabolism/therapy ; Dysbiosis/therapy ; Sciatic Nerve/injuries ; }, abstract = {Peripheral nerve injury (PNI) resulting from trauma or neuropathies can cause significant disability, and its prognosis deteriorates with age. Emerging evidence suggests that gut dysbiosis and reduced fecal short-chain fatty acids (SCFAs) contribute to an age-related systemic hyperinflammation (inflammaging), which hinders nerve recovery after injury. This study thus aimed to evaluate the pro-regenerative effects of a rejuvenating fecal microbiota transplant (FMT) in a preclinical PNI model using aged mice. Aged C57BL/6 mice underwent bilateral crush injuries to their sciatic nerves. Subsequently, they either received FMT from young donors at three and four days after the injury or retained their aged gut microbiota. We analyzed gut microbiome composition and SCFA concentrations in fecal samples. The integrity of the ileac mucosal barrier was assessed by immunofluorescence staining of Claudin-1. Flow cytometry was utilized to examine immune cells and cytokine production in the ileum, spleen, and sciatic nerve. Various assessments, including behavioural tests, electrophysiological studies, and morphometrical analyses, were conducted to evaluate peripheral nerve function and repair following injury. Rejuvenating FMT reversed age-related gut dysbiosis by increasing Actinobacteria, especially Bifidobacteriales genera. This intervention also led to an elevation of gut SCFA levels and mitigated age-related ileac mucosal leakiness in aged recipients. Additionally, it augmented the number of T-helper 2 (Th2) and regulatory T (Treg) cells in the ileum and spleen, with the majority being positive for anti-inflammatory interleukin-10 (IL-10). In sciatic nerves, rejuvenating FMT resulted in increased M2 macrophage counts and a higher IL-10 production by IL-10[+]TNF-α[-] M2 macrophage subsets. Ultimately, restoring a youthful gut microbiome in aged mice led to improved nerve repair and enhanced functional recovery after PNI. Considering that FMT is already a clinically available technique, exploring novel translational strategies targeting the gut microbiome to enhance nerve repair in the elderly seems promising and warrants further evaluation.}, }
@article {pmid38598636, year = {2024}, author = {Sizemore, N and Oliphant, K and Zheng, R and Martin, CR and Claud, EC and Chattopadhyay, I}, title = {A digital twin of the infant microbiome to predict neurodevelopmental deficits.}, journal = {Science advances}, volume = {10}, number = {15}, pages = {eadj0400}, pmid = {38598636}, issn = {2375-2548}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 HD105234/HD/NICHD NIH HHS/United States ; }, mesh = {Infant ; Humans ; Infant, Newborn ; Infant, Premature ; Artificial Intelligence ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Feces ; }, abstract = {Despite the recognized gut-brain axis link, natural variations in microbial profiles between patients hinder definition of normal abundance ranges, confounding the impact of dysbiosis on infant neurodevelopment. We infer a digital twin of the infant microbiome, forecasting ecosystem trajectories from a few initial observations. Using 16S ribosomal RNA profiles from 88 preterm infants (398 fecal samples and 32,942 abundance estimates for 91 microbial classes), the model (Q-net) predicts abundance dynamics with R[2] = 0.69. Contrasting the fit to Q-nets of typical versus suboptimal development, we can reliably estimate individual deficit risk (Mδ) and identify infants achieving poor future head circumference growth with ≈76% area under the receiver operator characteristic curve, 95% ± 1.8% positive predictive value at 98% specificity at 30 weeks postmenstrual age. We find that early transplantation might mitigate risk for ≈45.2% of the cohort, with potentially negative effects from incorrect supplementation. Q-nets are generative artificial intelligence models for ecosystem dynamics, with broad potential applications.}, }
@article {pmid38593970, year = {2024}, author = {Seida, I and Al Shawaf, M and Mahroum, N}, title = {Fecal microbiota transplantation in autoimmune diseases - An extensive paper on a pathogenetic therapy.}, journal = {Autoimmunity reviews}, volume = {23}, number = {7-8}, pages = {103541}, doi = {10.1016/j.autrev.2024.103541}, pmid = {38593970}, issn = {1873-0183}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Autoimmune Diseases/therapy/immunology/microbiology ; Gastrointestinal Microbiome/immunology ; Animals ; Inflammatory Bowel Diseases/therapy/immunology/microbiology ; }, abstract = {The role of infections in the pathogenesis of autoimmune diseases has long been recognized and reported. In addition to infectious agents, the internal composition of the "friendly" living bacteria, (microbiome) and its correlation to immune balance and dysregulation have drawn the attention of researchers for decades. Nevertheless, only recently, scientific papers regarding the potential role of transferring microbiome from healthy donor subjects to patients with autoimmune diseases has been proposed. Fecal microbiota transplantation or FMT, carries the logic of transferring microorganisms responsible for immune balance from healthy donors to individuals with immune dysregulation or more accurately for our paper, autoimmune diseases. Viewing the microbiome as a pathogenetic player allows us to consider FMT as a pathogenetic-based treatment. Promising results alongside improved outcomes have been demonstrated in patients with different autoimmune diseases following FMT. Therefore, in our current extensive review, we aimed to highlight the implication of FMT in various autoimmune diseases, such as inflammatory bowel disease, autoimmune thyroid and liver diseases, systemic lupus erythematosus, and type 1 diabetes mellitus, among others. Presenting all the aspects of FMT in more than 12 autoimmune diseases in one paper, to the best of our knowledge, is the first time presented in medical literature. Viewing FMT as such could contribute to better understanding and newer application of the model in the therapy of autoimmune diseases, indeed.}, }
@article {pmid38591915, year = {2024}, author = {Bratkovič, T and Zahirović, A and Bizjak, M and Rupnik, M and Štrukelj, B and Berlec, A}, title = {New treatment approaches for Clostridioides difficile infections: alternatives to antibiotics and fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2337312}, pmid = {38591915}, issn = {1949-0984}, mesh = {Humans ; Anti-Bacterial Agents/therapeutic use/pharmacology ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Vancomycin/pharmacology ; *Clostridium Infections/drug therapy/prevention &amp; control ; }, abstract = {Clostridioides difficile causes a range of debilitating intestinal symptoms that may be fatal. It is particularly problematic as a hospital-acquired infection, causing significant costs to the health care system. Antibiotics, such as vancomycin and fidaxomicin, are still the drugs of choice for C. difficile infections, but their effectiveness is limited, and microbial interventions are emerging as a new treatment option. This paper focuses on alternative treatment approaches, which are currently in various stages of development and can be divided into four therapeutic strategies. Direct killing of C. difficile (i) includes beside established antibiotics, less studied bacteriophages, and their derivatives, such as endolysins and tailocins. Restoration of microbiota composition and function (ii) is achieved with fecal microbiota transplantation, which has recently been approved, with standardized defined microbial mixtures, and with probiotics, which have been administered with moderate success. Prevention of deleterious effects of antibiotics on microbiota is achieved with agents for the neutralization of antibiotics that act in the gut and are nearing regulatory approval. Neutralization of C. difficile toxins (iii) which are crucial virulence factors is achieved with antibodies/antibody fragments or alternative binding proteins. Of these, the monoclonal antibody bezlotoxumab is already in clinical use. Immunomodulation (iv) can help eliminate or prevent C. difficile infection by interfering with cytokine signaling. Small-molecule agents without bacteriolytic activity are usually selected by drug repurposing and can act via a variety of mechanisms. The multiple treatment options described in this article provide optimism for the future treatment of C. difficile infection.}, }
@article {pmid38591029, year = {2024}, author = {Maurer, JJ and Cheng, Y and Pedroso, A and Thompson, KK and Akter, S and Kwan, T and Morota, G and Kinstler, S and Porwollik, S and McClelland, M and Escalante-Semerena, JC and Lee, MD}, title = {Peeling back the many layers of competitive exclusion.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1342887}, pmid = {38591029}, issn = {1664-302X}, support = {R35 GM130399/GM/NIGMS NIH HHS/United States ; }, abstract = {Baby chicks administered a fecal transplant from adult chickens are resistant to Salmonella colonization by competitive exclusion. A two-pronged approach was used to investigate the mechanism of this process. First, Salmonella response to an exclusive (Salmonella competitive exclusion product, Aviguard[®]) or permissive microbial community (chicken cecal contents from colonized birds containing 7.85 Log10Salmonella genomes/gram) was assessed ex vivo using a S. typhimurium reporter strain with fluorescent YFP and CFP gene fusions to rrn and hilA operon, respectively. Second, cecal transcriptome analysis was used to assess the cecal communities' response to Salmonella in chickens with low (≤5.85 Log10 genomes/g) or high (≥6.00 Log10 genomes/g) Salmonella colonization. The ex vivo experiment revealed a reduction in Salmonella growth and hilA expression following co-culture with the exclusive community. The exclusive community also repressed Salmonella's SPI-1 virulence genes and LPS modification, while the anti-virulence/inflammatory gene avrA was upregulated. Salmonella transcriptome analysis revealed significant metabolic disparities in Salmonella grown with the two different communities. Propanediol utilization and vitamin B12 synthesis were central to Salmonella metabolism co-cultured with either community, and mutations in propanediol and vitamin B12 metabolism altered Salmonella growth in the exclusive community. There were significant differences in the cecal community's stress response to Salmonella colonization. Cecal community transcripts indicated that antimicrobials were central to the type of stress response detected in the low Salmonella abundance community, suggesting antagonism involved in Salmonella exclusion. This study indicates complex community interactions that modulate Salmonella metabolism and pathogenic behavior and reduce growth through antagonism may be key to exclusion.}, }
@article {pmid38589422, year = {2024}, author = {Wei, N and Ju, M and Su, X and Zhang, Y and Huang, Y and Rao, X and Cui, L and Lin, Z and Dong, Y}, title = {Transplantation of gut microbiota derived from patients with schizophrenia induces schizophrenia-like behaviors and dysregulated brain transcript response in mice.}, journal = {Schizophrenia (Heidelberg, Germany)}, volume = {10}, number = {1}, pages = {44}, pmid = {38589422}, issn = {2754-6993}, support = {2022M711171//China Postdoctoral Science Foundation/ ; }, abstract = {Schizophrenia (SCZ), as a neurodevelopmental disorder and devastating disease, affects approximately 1% of the world population. Although numerous studies have attempted to elucidate the causes of SCZ occurrence, it is not clearly understood. Recently, the emerging roles of the gut microbiota in a range of brain disorders, including SCZ, have attracted much attention. While the molecular mechanism of gut microbiota in regulating the pathogenesis of SCZ is still lacking. Here, we first confirmed the difference of gut microbiome between SCZ patients and healthy controls, and then, we performed fecal microbiota transplantation (FMT) to clarify the roles of SCZ patients-derived microbiota in a specific pathogen free (SPF) mice model. 16 S rDNA sequencing confirmed that a significant difference of gut microbiome was present between two groups of FMT mice, which has a similar trend with the above human gut microbiome. Furthermore, we found that transplantation of fecal microbiota from SCZ patients into SPF mice was sufficient to induce schizophrenia-like (SCZ-like) symptoms, such as deficits in sociability and hyperactivity. Furthermore, the brains of mice colonized with SCZ microbiota displayed dysregulated transcript response and alternative splicing of SCZ-relevant genes. Moreover, 10 key genes were identified to be correlated with SCZ by an integrative transcriptome data analysis. Finally, 4 key genes were identified to be correlated with the 12 differential genera between two groups of FMT mice. Our results thus demonstrated that the gut microbiome might modify the transcriptomic profile in the brain, thereby modulating social behavior, and our present study can help better understand the link between gut microbiota and SCZ pathogenesis through the gut-brain axis.}, }
@article {pmid38589392, year = {2024}, author = {Dokoshi, T and Chen, Y and Cavagnero, KJ and Rahman, G and Hakim, D and Brinton, S and Schwarz, H and Brown, EA and O'Neill, A and Nakamura, Y and Li, F and Salzman, NH and Knight, R and Gallo, RL}, title = {Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3009}, pmid = {38589392}, issn = {2041-1723}, support = {R01 AR076082/AR/NIAMS NIH HHS/United States ; R01 DK128787/DK/NIDDK NIH HHS/United States ; R37 AI052453/AI/NIAID NIH HHS/United States ; T32 AI007036/AI/NIAID NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Hyaluronic Acid/metabolism ; *Colitis ; Intestinal Mucosa/metabolism ; Fecal Microbiota Transplantation ; Dextran Sulfate/toxicity ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/metabolism ; }, abstract = {The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.}, }
@article {pmid38589368, year = {2024}, author = {Liu, P and Liu, Z and Wang, J and Wang, J and Gao, M and Zhang, Y and Yang, C and Zhang, A and Li, G and Li, X and Liu, S and Liu, L and Sun, N and Zhang, K}, title = {Immunoregulatory role of the gut microbiota in inflammatory depression.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3003}, pmid = {38589368}, issn = {2041-1723}, mesh = {Animals ; Humans ; Mice ; Depression/therapy ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; }, abstract = {Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.}, }
@article {pmid38585738, year = {2024}, author = {Hunter, C and Dia, K and Boykins, J and Perry, K and Banerjee, N and Cuffee, J and Armstrong, E and Morgan, G and Banerjee, HN and Banerjee, A and Bhattacharya, S}, title = {An investigation for phylogenetic characterization of human Pancreatic cancer microbiome by 16SrDNA Sequencing and Bioinformatics techniques.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38585738}, issn = {2693-5015}, support = {T34 GM100831/GM/NIGMS NIH HHS/United States ; }, abstract = {Pancreatic cancer is a significant public health concern, with increasing incidence rates and limited treatment options. Recent studies have highlighted the role of the human microbiome, particularly the gut microbiota, in the development and progression of this disease. Microbial dysbiosis, characterized by alterations in the composition and function of the gut microbiota, has been implicated in pancreatic carcinogenesis through mechanisms involving chronic inflammation, immune dysregulation, and metabolic disturbances. Researchers have identified specific microbial signatures associated with pancreatic cancer, offering potential biomarkers for early detection and prognostication. By leveraging advanced sequencing and bioinformatics tools, scientists have delineated differences in the gut microbiota between pancreatic cancer patients and healthy individuals, providing insights into disease pathogenesis and potential diagnostic strategies. Moreover, the microbiome holds promise as a therapeutic target in pancreatic cancer treatment. Interventions aimed at modulating the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, have demonstrated potential in enhancing the efficacy of existing cancer therapies, including chemotherapy and immunotherapy. These approaches can influence immune responses, alter tumor microenvironments, and sensitize tumors to treatment, offering new avenues for improving patient outcomes and overcoming therapeutic resistance. Overall, understanding the complex interplay between the microbiome and pancreatic cancer is crucial for advancing our knowledge of disease mechanisms and identifying innovative therapeutic strategies. Here we report phylogenetic analysis of the 16S microbial sequences of the pancreatic cancer mice microbiome and corresponding age matched healthy mice microbiome. We successfully identified differentially abundance of microbiota in the pancreatic cancer.}, }
@article {pmid38585101, year = {2024}, author = {Verma, A and Bhagchandani, T and Rai, A and Nikita,  and Sardarni, UK and Bhavesh, NS and Gulati, S and Malik, R and Tandon, R}, title = {Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis-A Potential Therapeutic Intervention to Improve Lung Health.}, journal = {ACS omega}, volume = {9}, number = {13}, pages = {14648-14671}, pmid = {38585101}, issn = {2470-1343}, support = {D43 TW009345/TW/FIC NIH HHS/United States ; }, abstract = {The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut-lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut-lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.}, }
@article {pmid38584861, year = {2024}, author = {Biedermann, L and Kreienbühl, A and Rogler, G}, title = {Microbiota Therapy in Inflammatory Bowel Disease.}, journal = {Visceral medicine}, volume = {40}, number = {2}, pages = {92-101}, pmid = {38584861}, issn = {2297-4725}, abstract = {BACKGROUND: In both Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD) the immune reaction is - at least partially - directed against components of the luminal microbiota of the gut. These immune responses as well as other factors contribute to a phenomenon frequently described as "dysbiosis" meaning an alteration of the composition of the colonic microbiota. To improve the dysbiosis and to restore the normal composition of the colonic microbiota, fecal microbiota transplantation (FMT) has been tested as a therapeutic option to induce and maintain remission in IBD patients.<br><br>SUMMARY: This review will first discuss changes in the composition of the intestinal microbiota found in IBD patients and second the therapeutic potential of microbiological interventions for the treatment of these patients. FMT has been studied in several clinical trials in both, CD and UC. Reported results and subsequent meta-analyses indicate that FMT may be effective to induce remission in UC. However, the optimal route of FMT, the necessary number of administrations and the question whether life bacteria of freshly prepared stool is more effective than frozen are still unclear. Concepts associated with an optimization of FMT such as the "super donor concept" or the "consortia-approach" will be discussed to illustrate open questions and difficulties associated with microbiota therapy in IBD.<br><br>KEY MESSAGES: The microbiota composition in IBD patients shows significant alterations compared to healthy individuals termed as "dysbiosis". FMT and other therapeutic approaches to modify the microbiota composition have been studied in clinical trials in recent years. Efficacy has been shown in UC; however, many questions with respect to the optimization of microbiota therapy remain to be answered.}, }
@article {pmid38584858, year = {2024}, author = {Stallhofer, J and Steube, A and Katzer, K and Stallmach, A}, title = {Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent Clostridioides difficile Infection.}, journal = {Visceral medicine}, volume = {40}, number = {2}, pages = {82-91}, pmid = {38584858}, issn = {2297-4725}, abstract = {BACKGROUND: Clostridioides difficile (C. difficile) is a spore-forming bacterial species that ubiquitously exists in the environment. Colonization by C. difficile is highly prevalent in infants, while fewer than 5% of adults are asymptomatic carriers. Disruption of the microbiome, such as through antibiotic treatment, triggers the germination of bacterial spores into numerous vegetative cells. These cells then produce enterotoxins that result in watery diarrhea and colonic inflammation. If left untreated, C. difficile infection (CDI) can lead to pseudomembranous colitis with the potentially life-threatening complication of toxic megacolon.<br><br>SUMMARY: Over the past few decades, the incidence, morbidity, and mortality associated with CDIs have increased. They have emerged as the primary cause of nosocomial gastrointestinal infections in industrialized countries, posing a significant burden on healthcare systems. Despite antibiotics often being the cause of CDIs, they remain the standard treatment. However, a considerable number of patients treated with antibiotics will experience recurrent CDI (rCDI). Microbiota-based therapies targeting the core issue of CDI - antibiotic-induced dysbiosis - hold promise for rCDI treatment. While data for probiotics are insufficient, numerous studies have highlighted the effectiveness of fecal microbiota transplantation (FMT) as a safe and viable therapeutic option for rCDI. This approach is now endorsed by multiple guidelines. Nonetheless, regulatory prerequisites, such as comprehensive stool donor screening, restrict the widespread adoption of FMT beyond specialized centers. Recently, the US Food and Drug Administration has approved two commercial microbiota-based therapeutics to prevent CDI recurrence. These therapeutics are available by prescription in the USA. RBX2660 (REBYOTA&#x2122;) comprises a diverse consortium of live microbes derived from human stool and is administered via enema. On the other hand, SER-109 (VOWST&#x2122;) is an orally administered spore-based medication. In this review, we discuss the potential of microbiota-based treatments for rCDI against the background of medico-legal challenges associated with classical FMT.<br><br>KEY MESSAGES: FMT has emerged as a highly effective cure for rCDI. Nonetheless, regulatory prerequisites and laborious preparation procedures impede its widespread use. The establishment of ready-to-use microbiota-based therapeutics in clinical practice is necessary. In the USA, the recent approval of the first two commercial medications, including a spore-based oral preparation, marks a significant step forward.}, }
@article {pmid38584284, year = {2024}, author = {Chen, C and Xu, JL and Gu, ZC and Zhou, SS and Wei, GL and Gu, JL and Ma, HL and Feng, YQ and Song, ZW and Yan, ZP and Deng, S and Ding, R and Li, SL and Huo, JG}, title = {Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.}, journal = {Chinese medicine}, volume = {19}, number = {1}, pages = {58}, pmid = {38584284}, issn = {1749-8546}, support = {82004339//Natural Science Foundation of China/ ; Z2022005//Medical Scientific Research Project of Jiangsu Provincial Health Commission/ ; No.2021.6//Jiangsu Clinical Innovation Center of Digestive Cancer of Traditional Chinese Medicine/ ; JD2019SZXYB16//Project of National Clinical Research Base of Traditional Chinese Medicine in Jiangsu Province/ ; BE2019767//Jiangsu science and technology department social development-clinical frontier technology/ ; BRA2019100//Jiangsu science and technology department social development-clinical frontier technology/ ; BK20210984//Natural Science Foundation of Jiangsu Province/ ; }, abstract = {BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated.<br><br>METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation.<br><br>RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-&#x3b1;. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota.<br><br>CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.}, }
@article {pmid38582194, year = {2024}, author = {Rook, GAW}, title = {Evolution and the critical role of the microbiota in the reduced mental and physical health associated with low socioeconomic status (SES).}, journal = {Neuroscience and biobehavioral reviews}, volume = {161}, number = {}, pages = {105653}, doi = {10.1016/j.neubiorev.2024.105653}, pmid = {38582194}, issn = {1873-7528}, mesh = {Humans ; *Biological Evolution ; Brain-Gut Axis/physiology ; *Gastrointestinal Microbiome/physiology ; Low Socioeconomic Status ; Mental Disorders/microbiology ; Mental Health ; *Social Class ; }, abstract = {The evolution of the gut-microbiota-brain axis in animals reveals that microbial inputs influence metabolism, the regulation of inflammation and the development of organs, including the brain. Inflammatory, neurodegenerative and psychiatric disorders are more prevalent in people of low socioeconomic status (SES). Many aspects of low SES reduce exposure to the microbial inputs on which we are in a state of evolved dependence, whereas the lifestyle of wealthy citizens maintains these exposures. This partially explains the health deficit of low SES, so focussing on our evolutionary history and on environmental and lifestyle factors that distort microbial exposures might help to mitigate that deficit. But the human microbiota is complex and we have poor understanding of its functions at the microbial and mechanistic levels, and in the brain. Perhaps its composition is more flexible than the microbiota of animals that have restricted habitats and less diverse diets? These uncertainties are discussed in relation to the encouraging but frustrating results of attempts to treat psychiatric disorders by modulating the microbiota.}, }
@article {pmid38579995, year = {2024}, author = {Zeng, Z and Lv, B and Tang, YE and Sun, H and Li, S and He, Y and Wang, J and Wang, Z}, title = {Effects of dietary selenized glucose on intestinal microbiota and tryptophan metabolism in rats: Assessing skatole reduction potential.}, journal = {Environmental research}, volume = {252}, number = {Pt 3}, pages = {118874}, doi = {10.1016/j.envres.2024.118874}, pmid = {38579995}, issn = {1096-0953}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Skatole/metabolism ; Male ; *Tryptophan/metabolism ; *Rats, Sprague-Dawley ; Rats ; *Glucose/metabolism ; Selenium/pharmacology ; Diet ; }, abstract = {3-Methylindole (Skatole), a degradation product of tryptophan produced by intestinal microbial activity, significantly contributes to odor nuisance. Its adverse effects on animal welfare, human health, and environmental pollution have been noted. However, it is still unclear whether the intestinal microbiota mediates the impact of selenium (Se) on skatole production and what the underlying mechanisms remain elusive. A selenized glucose (SeGlu) derivative is a novel organic selenium compound. In this study, a diverse range of dietary SeGlu-treated levels, including SeGlu-deficient (CK), SeGlu-adequate (0.15 mg Se per L), and SeGlu-supranutritional (0.4 mg Se per L) conditions, were used to investigate the complex interaction of SeGlu on intestinal microbiome and serum metabolome changes in male Sprague-Dawley (SD) rats. The study showed that SeGlu supplementation enhanced the antioxidant ability in rats, significantly manifested in the increases of the activity of catalase (CAT) and glutathione peroxidase (GSH-Px), while no change in the level of malonaldehyde (MDA). Metagenomic sequencing analysis verified that the SeGlu treatment group significantly increased the abundance of beneficial microorganisms such as Clostridium, Ruminococcus, Faecalibacterium, Lactobacillus, and Alloprevotella while reducing the abundance of opportunistic pathogens such as Bacteroides and Alistipes significantly. Further metabolomic analysis revealed phenylalanine, tyrosine, and tryptophan biosynthesis changes in the SeGlu treatment group. Notably, the biosynthesis of indole, a critical pathway, was affected by SeGlu treatment, with several crucial enzymes implicated. Correlation analysis demonstrated strong associations between specific bacterial species - Treponema, Bacteroides, and Ruminococcus, and changes in indole and derivative concentrations. Moreover, the efficacy of SeGlu-treated fecal microbiota was confirmed through fecal microbiota transplantation, leading to a decrease in the concentration of skatole in rats. Collectively, the analysis of microbiota and metabolome response to diverse SeGlu levels suggests that SeGlu is a promising dietary additive in modulating intestinal microbiota and reducing odor nuisance in the livestock and poultry industry.}, }
@article {pmid38579985, year = {2025}, author = {Tao, W and Zhang, Y and Wang, B and Nie, S and Fang, L and Xiao, J and Wu, Y}, title = {Advances in molecular mechanisms and therapeutic strategies for central nervous system diseases based on gut microbiota imbalance.}, journal = {Journal of advanced research}, volume = {69}, number = {}, pages = {261-278}, pmid = {38579985}, issn = {2090-1224}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Central Nervous System Diseases/therapy/microbiology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation/methods ; Prebiotics/administration &amp; dosage ; *Dysbiosis/microbiology ; Mice ; }, abstract = {BACKGROUD: Central nervous system (CNS) diseases pose a serious threat to human health, but the regulatory mechanisms and therapeutic strategies of CNS diseases need to be further explored. It has been demonstrated that the gut microbiota (GM) is closely related to CNS disease. GM structure disorders, abnormal microbial metabolites, intestinal barrier destruction and elevated inflammation exist in patients with CNS diseases and promote the development of CNS diseases. More importantly, GM remodeling alleviates CNS pathology to some extent.<br><br>AIM OF REVIEW: Here, we have summarized the regulatory mechanism of the GM in CNS diseases and the potential treatment strategies for CNS repair based on GM regulation, aiming to provide safer and more effective strategies for CNS repair from the perspective of GM regulation.<br><br>The abundance and composition of GM is closely associated with the CNS diseases. On the basis of in-depth analysis of GM changes in mice with CNS disease, as well as the changes in its metabolites, therapeutic strategies, such as probiotics, prebiotics, and FMT, may be used to regulate GM balance and affect its microbial metabolites, thereby promoting the recovery of CNS diseases.}, }
@article {pmid38578736, year = {2024}, author = {Lin, L and Xu, S and Cai, M and Li, S and Chen, Y and Chen, L and Lin, Y}, title = {Effects of fecal microbiota transfer on blood pressure in animal models: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {19}, number = {4}, pages = {e0300869}, pmid = {38578736}, issn = {1932-6203}, mesh = {*Fecal Microbiota Transplantation ; *Blood Pressure/physiology ; Animals ; *Hypertension/microbiology/physiopathology ; *Gastrointestinal Microbiome ; Disease Models, Animal ; Feces/microbiology ; Humans ; }, abstract = {BACKGROUND: Numerous recent studies have found a strong correlation between intestinal flora and the occurrence of hypertension. However, it remains unclear whether fecal microbiota transfer might affect the blood pressure of the host. This study aimed to quantify both associations.<br><br>METHODS: An electronic search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu, Embase, and SinoMed to retrieve relevant studies. The final search was completed on August 22, 2022. Two authors independently applied the inclusion criteria, extracted data, and assessed the risk of bias assessment. All data were analyzed using RevMan 5.4.<br><br>RESULTS: A total of 5 articles were selected for final inclusion. All studies were assessed as having a high risk of bias according to the SYRCLE risk of bias tool. The meta-analysis results showed that transplantation of fecal bacteria from the hypertensive model can significantly improve the host's systolic pressure (MD = 18.37, 95%CI: 9.74~26.99, P<0.001), and diastolic pressure (MD = 17.65, 95%CI: 12.37~22.93, P<0.001). Subgroup analyses revealed that the increase in systolic pressure in the hypertension model subgroup (MD = 29.56, 95%CI = 23.55-35.58, P<0.001) was more pronounced than that in the normotensive model subgroup (MD = 12.48, 95%CI = 3.51-21.45, P<0.001).<br><br>CONCLUSION: This meta-analysis suggests a relationship between gut microbiota dysbiosis and increased blood pressure, where transplantation of fecal bacteria from the hypertensive model can cause a significant increase in systolic pressure and diastolic pressure in animal models.}, }
@article {pmid38577203, year = {2024}, author = {Koutromanos, I and Legaki, E and Gazouli, M and Vasilopoulos, E and Kouzoupis, A and Tzavellas, E}, title = {Gut microbiome in alcohol use disorder: Implications for health outcomes and therapeutic strategies-a literature review.}, journal = {World journal of methodology}, volume = {14}, number = {1}, pages = {88519}, pmid = {38577203}, issn = {2222-0682}, abstract = {Alcohol use disorder (AUD) represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality. The gut microbiome plays a crucial role in maintaining overall health and has emerged as a significant contributor to the pathophysiology of various psychiatric disorders. Recent evidence suggests that the gut microbiome is intimately linked to the development and progression of AUD, with alcohol consumption directly impacting its composition and function. This review article aims to explore the intricate relationship between the gut microbiome and AUD, focusing on the implications for mental health outcomes and potential therapeutic strategies. We discuss the bidirectional communication between the gut microbiome and the brain, highlighting the role of microbiota-derived metabolites in neuroinflammation, neurotransmission, and mood regulation. Furthermore, we examine the influence of AUD-related factors, such as alcohol-induced gut dysbiosis and increased intestinal permeability, on mental health outcomes. Finally, we explore emerging therapeutic avenues targeting the gut microbiome in the management of AUD, including prebiotics, probiotics, and fecal microbiota transplantation. Understanding the complex interplay between the gut microbiome and AUD holds promise for developing novel interventions that could improve mental health outcomes in individuals with AUD.}, }
@article {pmid38575121, year = {2024}, author = {Ren, J and Li, Y and Ni, H and Zhang, Y and Zhao, P and Xiao, Q and Hong, X and Zhang, Z and Yin, Y and Li, X and Zhang, Y and Yang, Y}, title = {Gut microbiota derived from fecal microbiota transplantation enhances body weight of Mimas squabs.}, journal = {Animal bioscience}, volume = {37}, number = {8}, pages = {1428-1439}, pmid = {38575121}, issn = {2765-0189}, support = {YDZJ202301ZYTS355//Provincial Scientific and Technological Development Program/ ; 20210101362JC//Natural Science Foundation of Jilin Province of China/ ; 20230505047ZP//Jilin Province Science and Technology Development Plan Project/ ; }, abstract = {OBJECTIVE: Compared to Mimas pigeons, Shiqi pigeons exhibit greater tolerance to coarse feeding because of their abundant gut microbiota. Here, to investigate the potential of utilizing intestinal flora derived from Shiqi pigeons, the intestinal flora and body indices of Mimas squabs were evaluated after fecal microbiota transplantation (FMT) from donors.<br><br>METHODS: A total of 90 one-day-old squabs were randomly divided into the control group (CON), the low-concentration group (LC) and the high-concentration group (HC): gavaged with 200 &#x3bc;L of bacterial solution at concentrations of 0, 0.1, and 0.2 g/15 mL, respectively.<br><br>RESULTS: The results suggested that FMT improved the body weight of Mimas squabs in the HC and LC groups (p<0.01), and 0.1 g/15 mL was the optimal dose during FMT. After 16S rRNA sequencing was performed, compared to those in the CON group, the abundance levels of microflora, especially Lactobacillus, Muribaculaceae, and Megasphaera (p<0.05), in the FMT-treated groups were markedly greater. Random forest analysis indicated that the main functions of key microbes involve pathways associated with metabolism, further illustrating their important role in the host body.<br><br>CONCLUSION: FMT has been determined to be a viable method for augmenting the weight and intestinal microbiota of squabs, representing a unique avenue for enhancing the economic feasibility of squab breeding.}, }
@article {pmid38574899, year = {2024}, author = {Stevens, LJ and van de Steeg, E and Doppenberg, JB and Alwayn, IPJ and Knibbe, CAJ and Dubbeld, J}, title = {Ex vivo gut-hepato-biliary organ perfusion model to characterize oral absorption, gut-wall metabolism, pre-systemic hepatic metabolism and biliary excretion; application to midazolam.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {196}, number = {}, pages = {106760}, doi = {10.1016/j.ejps.2024.106760}, pmid = {38574899}, issn = {1879-0720}, mesh = {Animals ; *Midazolam/pharmacokinetics/administration &amp; dosage/metabolism ; *Liver/metabolism ; Perfusion ; Swine ; *Intestinal Absorption ; Administration, Oral ; Bile/metabolism ; Hepatobiliary Elimination ; *Biliary Tract/metabolism ; Atenolol/pharmacokinetics/administration &amp; dosage ; Portal Vein/metabolism ; Intestinal Mucosa/metabolism ; Feces/chemistry ; Antipyrine/pharmacokinetics ; Models, Biological ; }, abstract = {To date, characterization of the first-pass effect of orally administered drugs consisting of local intestinal absorption and metabolism, portal vein transport and hepatobiliary processes remains challenging. Aim of this study was to explore the applicability of a porcine ex-vivo perfusion model to study oral absorption, gut-hepatobiliary metabolism and biliary excretion of midazolam. Slaughterhouse procured porcine en bloc organs (n = 4), were perfused via the aorta and portal vein. After 120 min of perfusion, midazolam, atenolol, antipyrine and FD4 were dosed via the duodenum and samples were taken from the systemic- and portal vein perfusate, intestinal faecal effluent and bile to determine drug and metabolite concentrations. Stable arterial and portal vein flow was obtained and viability of the perfused organs was confirmed. After intraduodenal administration, midazolam was rapidly detected in the portal vein together with 1-OH midazolam (EG-pv of 0.16±0.1) resulting from gut wall metabolism through oxidation. In the intestinal faecal effluent, 1-OH midazolam and 1-OH midazolam glucuronide (EG-intestine 0.051±0.03) was observed resulting from local gut glucuronidation. Biliary elimination of midazolam (0.04±0.01 %) and its glucuronide (0.01±0.01 %) only minimally contributed to the enterohepatic circulation. More extensive hepatic metabolism (FH 0.35±0.07) over intestinal metabolism (FG 0.78±0.11) was shown, resulting in oral bioavailability of 0.27±0.05. Ex vivo perfusion demonstrated to be a novel approach to characterize pre-systemic extraction of midazolam by measuring intestinal as well as hepatic extraction. The model can generate valuable insights into the absorption and metabolism of new drugs.}, }
@article {pmid38574779, year = {2024}, author = {Yan, G and Zhang, L and Wu, D and Jiang, S and Wu, Q and Dai, M}, title = {Paeonol attenuates nonalcoholic steatohepatitis by regulating intestinal flora and AhR/NLRP3/Caspase-1 metabolic pathway.}, journal = {Journal of ethnopharmacology}, volume = {329}, number = {}, pages = {118147}, doi = {10.1016/j.jep.2024.118147}, pmid = {38574779}, issn = {1872-7573}, mesh = {*Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; Animals ; *Acetophenones/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Male ; Mice ; *Mice, Inbred C57BL ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Receptors, Aryl Hydrocarbon/metabolism ; *Caspase 1/metabolism ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Disease Models, Animal ; Liver/drug effects/metabolism ; Signal Transduction/drug effects ; Metabolic Networks and Pathways/drug effects ; }, abstract = {Non-alcoholic steatohepatitis (NASH) is a common metabolic liver injury disease that is closely associated with obesity and metabolic disorders. Paeonol, an active ingredient found in Moutan Cortex, a traditional Chinese medicine which exhibits significant therapeutic effect on liver protection, has shown promising effects in treating liver diseases, particularly NASH. However, the specific intervention mechanism of paeonol on NASH is still unknown.<br><br>AIM OF THE STUDY: Our objective is to elucidate the pharmacological mechanism of paeonol in intervening NASH at the in vivo level, focusing on the impact on intestinal flora, tryptophan-related targeted metabolome, and related Aryl hydrocarbon receptor (AhR) pathways.<br><br>MATERIALS AND METHODS: Here, we explored the intervention effect of paeonol on NASH by utilizing the NASH mouse model. The Illumina highthroughput sequencing technology was preformed to determine the differences of gut microbiota of model and paeonol treatment group. The concentration of Indoleacetic acid is determined by ELISA. The intervention effect of NASH mouse and AhR/NLRP3/Caspase-1 metabolic pathway is analyzed by HE staining, oil red O staining, Immunohistochemistry, Immunofluorescence, Western blot and qRT-PCR assays. Fecal microbiota transplantation experiment also was performed to verify the intervention effect of paeonol on NASH by affecting gut microbiota.<br><br>RESULTS: Firstly, we discovered that paeonol effectively reduced liver pathology and blood lipid levels in NASH mice, thereby intervening in the progression of NASH. Subsequently, through 16S meta-analysis, we identified that paeonol can effectively regulate the composition of intestinal flora in NASH mice, transforming it to resemble that of normal mice. Specifically, paeonol decreased the abundance of certain Gram-negative tryptophan-metabolizing bacteria. Moreover, we discovered that paeonol significantly increased the levels of metabolites Indoleacetic acid, subsequently enhancing the expression of AhR-related pathway proteins. This led to the inhibition of the NOD-like receptor protein 3 (NLRP3) inflammasome production and inflammation generation in NASH. Lastly, we verified the efficacy of paeonol in intervening NASH by conducting fecal microbiota transplantation experiments, which confirmed its role in promoting the AhR/NLRP3/cysteinyl aspartate specific proteinase (Caspase-1) pathway.<br><br>CONCLUSIONS: Our findings suggest that paeonol can increase the production of Indoleacetic acid by regulating the gut flora, and promote the AhR/NLRP3/Caspase-1 metabolic pathway to intervene NASH.}, }
@article {pmid38574772, year = {2024}, author = {Sottil, P and Lhomme, S and Saune, K and El Hayani, S and Oliveira-Mendes, K and Peron, JM and Kamar, N and Izopet, J and Abravanel, F}, title = {Evaluation of an automated platform for the detection of HEV RNA in plasma and stool.}, journal = {Journal of virological methods}, volume = {327}, number = {}, pages = {114920}, doi = {10.1016/j.jviromet.2024.114920}, pmid = {38574772}, issn = {1879-0984}, mesh = {*Feces/virology ; Humans ; *RNA, Viral/isolation &amp; purification/blood/analysis/genetics ; *Hepatitis E virus/isolation &amp; purification/genetics ; *Hepatitis E/diagnosis/virology/blood ; *Automation, Laboratory ; Sensitivity and Specificity ; Plasma/virology ; Molecular Diagnostic Techniques/methods ; }, abstract = {INTRODUCTION: We evaluated the performance of the automated Altostar HEV RNA platform for detecting HEV RNA.<br><br>METHODS AND RESULTS: Clinical performance was determined by testing 81 plasma samples and 10 fecal samples manually quantified previously with the Realstar RT-PCR assay using the Magnapure instrument for extraction. The assays were concordant for 79/81 plasma samples (97.5%) and 10/10 (100%) fecal samples. The two plasma samples that tested negative with the Altostar assay had a very low HEV RNA concentration (1.6 and 1.4&#x202f;log10 IU/ml). Quantitative results obtained with the automated platform and the manual workflow were highly correlated (&#x3c1;= 0.98, p<0.01). The intra-run and inter-run standard deviation were 0.09 IU/ml and 0.13 IU/ml respectively. The assay was linear from 2 to 6&#x202f;log IU/ml. The limit of detection determined by Probit analysis with the WHO HEV RNA standard was 7.6 [95% CI: 4.4-52.5] IU/ml.<br><br>CONCLUSIONS: The Altostar platform enables highly accurate testing for the detection of HEV RNA in stool and the quantification of HEV RNA in plasma. This allowed us to shorten turnaround times and to save time for the technical staff.}, }
@article {pmid38572783, year = {2024}, author = {Ren, S and Feng, L and Liu, H and Mao, Y and Yu, Z}, title = {Gut microbiome affects the response to immunotherapy in non-small cell lung cancer.}, journal = {Thoracic cancer}, volume = {15}, number = {14}, pages = {1149-1163}, pmid = {38572783}, issn = {1759-7714}, support = {ZR202102240880//Natural Science Foundation of Shandong Province/ ; 23-2-1-189-zyyd-jch//Natural Science Foundation of Qingdao Municipality/ ; 320.6750.2021-02-92//Wu Jieping Medical Foundation/ ; 82373170//National Natural Science Foundation of China/ ; Y-QL202101-0258//Chinese Society of Clinical Oncology/ ; Y-pierrefabre202101-0074//Chinese Society of Clinical Oncology/ ; YXH2022ZX02020//ShanDong Provincial Medical Association/ ; }, mesh = {*Carcinoma, Non-Small-Cell Lung/therapy ; *Gastrointestinal Microbiome ; Animals ; Mice ; Humans ; *Lung Neoplasms/therapy ; *Immunotherapy/methods ; Female ; Male ; Middle Aged ; Aged ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; }, abstract = {BACKGROUND: Immunotherapy has revolutionized cancer treatment. Recent studies have suggested that the efficacy of immunotherapy can be further enhanced by the influence of gut microbiota. In this study, we aimed to investigate the impact of bacteria on the effectiveness of cancer immunotherapy by combining analysis of clinical samples with validation in animal models.<br><br>METHODS: In order to characterize the diversity and composition of microbiota and its relationship with response to immune checkpoint inhibitors (ICIs), 16S ribosomal RNA (rRNA) and GC-MS sequencing was performed on 71 stool samples from patients with advanced non-small cell lung cancer (NSCLC) prior to treatment with immune checkpoint blockade (ICB). Furthermore, fecal microbiota transplantation (FMT) was performed from different patients into mice and a subcutaneous tumor model established using the Lewis lung cancer cell line to evaluate the therapeutic effect of PD-1 on mice with varying gut microbiota.<br><br>RESULTS: The results demonstrated a significant association between elevated gut microbiota diversity and response to treatment with ICIs, p&#x2009;<&#x2009;0.05. Faecalibacterium was markedly increased in the gut microbiota of responders (R), accompanied by increased short-chain fatty acid (SCFA) levels, especially butanoic acid, acetic acid and hexanoic acid, p&#x2009;<&#x2009;0.05. Additionally, FMT from R and nonresponders (NR) could promote an anticancer effect and reduce the expression of Ki-67 cells in tumors in mice, p&#x2009;<&#x2009;0.05. Moreover, R and NR FMT did not alter PD-L1 expression in the tumor tissues of mice, p > 0.05. The diversity of gut microbiota consistently correlated with an optimistic prognosis in NSCLC patients with immunotherapy, which could be functionally mediated by SCFAs.<br><br>CONCLUSION: The findings of the present study indicated that the diversity of gut microbiota and SCFAs is related to the efficacy of immunotherapy. FMT can effectively delay tumor progression, and enhance the effect of immunotherapy, thus providing evidence for improving the efficacy of immunotherapy in NSCLC patients.}, }
@article {pmid38572716, year = {2024}, author = {van Lingen, E and Nooij, S and Terveer, EM and Crossette, E and Prince, AL and Bhattarai, SK and Watson, A and Galazzo, G and Menon, R and Szabady, RL and Bucci, V and Norman, JM and van der Woude, CJ and van der Marel, S and Verspaget, HW and van der Meulen-de Jong, AE and Keller, JJ}, title = {Faecal Microbiota Transplantation Engraftment After Budesonide or Placebo in Patients With Active Ulcerative Colitis Using Pre-selected Donors: A Randomized Pilot Study.}, journal = {Journal of Crohn's &amp; colitis}, volume = {18}, number = {9}, pages = {1381-1393}, pmid = {38572716}, issn = {1876-4479}, support = {//Vedanta Biosciences/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Budesonide/therapeutic use/administration &amp; dosage ; *Colitis, Ulcerative/therapy/microbiology ; Female ; Male ; Adult ; Pilot Projects ; Middle Aged ; Treatment Outcome ; Gastrointestinal Microbiome/drug effects ; Double-Blind Method ; Donor Selection/methods ; Anti-Inflammatory Agents/therapeutic use ; Feces/microbiology ; }, abstract = {BACKGROUND: Faecal microbiota transplantation [FMT] shows some efficacy in treating patients with ulcerative colitis [UC], although variability has been observed among donors and treatment regimens. We investigated the effect of FMT using rationally selected donors after pretreatment with budesonide or placebo in active UC.<br><br>METHODS: Patients &#x2265;18 years old with mild to moderate active UC were randomly assigned to 3 weeks of budesonide [9 mg] or placebo followed by 4-weekly infusions of a donor faeces suspension. Two donors were selected based on microbiota composition, regulatory T cell induction and short-chain fatty acid production in mice. The primary endpoint was engraftment of donor microbiota after FMT. In addition, clinical efficacy was assessed.<br><br>RESULTS: In total, 24 patients were enrolled. Pretreatment with budesonide did not increase donor microbiota engraftment [p&#x2005;=&#x2005;0.56] nor clinical response, and engraftment was not associated with clinical response. At week 14, 10/24 [42%] patients achieved [partial] remission. Remarkably, patients treated with FMT suspensions from one donor were associated with clinical response [80% of responders, p&#x2005;<&#x2005;0.05] but had lower overall engraftment of donor microbiota. Furthermore, differences in the taxonomic composition of the donors and the engraftment of certain taxa were associated with clinical response.<br><br>CONCLUSION: In this small study, pretreatment with budesonide did not significantly influence engraftment or clinical response after FMT. However, clinical response appeared to be donor-dependent. Response to FMT may be related to transfer of specific strains instead of overall engraftment, demonstrating the need to characterize mechanisms of actions of strains that maximize therapeutic benefit in UC.}, }
@article {pmid38571533, year = {2024}, author = {Al Naser, Y and AlGashami, M and Aljashaami, L}, title = {Clostridioides difficile infection: a changing treatment paradigm.}, journal = {Przeglad gastroenterologiczny}, volume = {19}, number = {1}, pages = {1-5}, pmid = {38571533}, issn = {1895-5770}, abstract = {Clostridioides difficile infection (CDI) poses a persistent challenge in healthcare, with substantial morbidity and mortality implications. This comprehensive review explores current CDI management, emphasising guidelines from IDSA, SHEA, and ESCMID. Additionally, this study spotlights recent drug developments that have the potential to reshape CDI treatment paradigms. Within the current treatment landscape, fidaxomicin, vancomycin, bezlotoxumab, and faecal microbiota transplantation offer varied options, each with its unique strengths and limitations. Fidaxomicin, effective yet resource-constrained, presents a dilemma, with vancomycin emerging as a pragmatic alternative. Bezlotoxumab, though augmenting antibiotics, grapples with cost and safety concerns. Meanwhile, faecal microbiota transplantation, highly efficacious, confronts evolving safety considerations. The horizon of CDI treatment also features promising therapies such as SER-109 and Rebyota, epitomising the evolving paradigm. As CDI management advances, the critical role of standardised microbiome restoration therapies becomes evident, ensuring long-term safety and diversifying treatment strategies.}, }
@article {pmid38570412, year = {2024}, author = {Menozzi, E and Schapira, AHV}, title = {The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications.}, journal = {CNS drugs}, volume = {38}, number = {5}, pages = {315-331}, pmid = {38570412}, issn = {1179-1934}, support = {ASAP-000420//Aligning Science Across Parkinson's/ ; }, mesh = {Humans ; *Parkinson Disease/drug therapy ; *Gastrointestinal Microbiome/physiology ; Levodopa/pharmacology ; Dopamine ; *Helicobacter Infections ; *Helicobacter pylori ; }, abstract = {The concept of a 'microbiota-gut-brain axis' has recently emerged as an important player in the pathophysiology of Parkinson disease (PD), not least because of the reciprocal interaction between gut bacteria and medications. The gut microbiota can influence levodopa kinetics, and conversely, drugs administered for PD can influence gut microbiota composition. Through a two-step enzymatic pathway, gut microbes can decarboxylate levodopa to dopamine in the small intestine and then dehydroxylate it to m-tyramine, thus reducing availability. Inhibition of bacterial decarboxylation pathways could therefore represent a strategy to increase levodopa absorption. Other bacterial perturbations common in PD, such as small intestinal bacterial overgrowth and Helicobacter pylori infection, can also modulate levodopa metabolism, and eradication therapies may improve levodopa absorption. Interventions targeting the gut microbiota offer a novel opportunity to manage disabling motor complications and dopa-unresponsive symptoms. Mediterranean diet-induced changes in gut microbiota composition might improve a range of non-motor symptoms. Prebiotics can increase levels of short-chain fatty acid-producing bacteria and decrease pro-inflammatory species, with positive effects on clinical symptoms and levodopa kinetics. Different formulations of probiotics showed beneficial outcomes on constipation, with some of them improving dopamine levels; however, the most effective dosage and duration and long-term effects of these treatments remain unknown. Data from faecal microbiota transplantation studies are preliminary, but show encouraging trends towards improvement in both motor and non-motor outcomes.This article summarises the most up-to-date knowledge in pharmacomicrobiomics in PD, and discusses how the manipulation of gut microbiota represents a potential new therapeutic avenue for PD.}, }
@article {pmid38567141, year = {2024}, author = {Hopper, AL and Hudson, CL and Klair, D and Ding, Q and Gao, Z and Jha, A and Bryan, A and Tikekar, RV and Coolong, T and Dunn, LL and Micallef, SA}, title = {Rain splash-mediated dispersal of Escherichia coli from fecal deposits to field-grown lettuce in the mid- and south Atlantic U.S. regions is affected by mulch type.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1370495}, pmid = {38567141}, issn = {1664-462X}, abstract = {INTRODUCTION: Wildlife feces can contaminate vegetables when enteric bacteria are released by rain and splashed onto crops. Regulations require growers to identify and not harvest produce that is likely contaminated, but U.S. federal standards do not define dimensions for no-harvest zones. Moreover, mulching, used to retain soil moisture and maximize crop yield may impact rain-mediated bacterial dispersal from feces.<br><br>METHODS: To assess Escherichia coli dissemination from a fecal point source to lettuce grown on various mulches, lettuce cv. 'Magenta' was transplanted into raised beds with plastic, biodegradable plastic, straw, or left uncovered at field sites in Maryland and Georgia. Eleven days post-transplant, 10&#xa0;g of rabbit manure spiked with ~8 log CFU g[-1] E. coli were deposited in each bed. One day following natural or simulated rain events, lettuce was sampled along 1.5&#xa0;m transects on either side of fecal deposits. Lettuce-associated E. coli was semi-quantified with an MPN assay and dependence on fecal age (stale or fresh), lettuce age (baby leaf or mature head), distance from point source, mulch and post-rain days were statistically evaluated.<br><br>RESULTS: Distance (p<0.001), fecal age (p<0.001) and mulch (p<0.01) were factors for E. coli transfer from point source to lettuce. The highest and lowest E. coli estimates were measured from lettuce grown on biodegradable plastic and straw, respectively, with a 2-log MPN difference (p<0.001). Mulch and distance were also significant factors in E. coli recovery 3 days post-rain (both p<0.001), where plastic mulches differed from bare ground and straw (p<0.01). For all treatments, fewer E. coli were retrieved from lettuce at 0.3&#xa0;m, 3 days post-rain compared to 1 day (p<0.001). Fitting the data to a Weibull Model predicated that a 7-log reduction in E. coli from fecal levels would be achieved at 1.2-1.4&#xa0;m from the point source on plastic mulches, 0.75&#xa0;m on bare soil (p<0.05) and 0.43&#xa0;m on straw (p<0.01).<br><br>DISCUSSION: Straw and bare ground limited rain-mediated E. coli dispersal from feces to lettuce compared to plastic mulches. Fecal age was negatively associated with E. coli dispersal. These findings can inform harvesting recommendations for measures related to animal intrusion in vegetable production areas.}, }
@article {pmid38565581, year = {2024}, author = {Boussamet, L and Montassier, E and Mathé, C and Garcia, A and Morille, J and Shah, S and Dugast, E and Wiertlewski, S and Gourdel, M and Bang, C and Stürner, KH and Masson, D and Nicot, AB and Vince, N and Laplaud, DA and Feinstein, DL and Berthelot, L}, title = {Investigating the metabolite signature of an altered oral microbiota as a discriminant factor for multiple sclerosis: a pilot study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {7786}, pmid = {38565581}, issn = {2045-2322}, support = {I01 BX002625/BX/BLRD VA/United States ; I21 BX005914/BX/BLRD VA/United States ; IK6 BX004852/BX/BLRD VA/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Multiple Sclerosis ; Pilot Projects ; RNA, Ribosomal, 16S/genetics/analysis ; *Microbiota/genetics ; Bacteria/genetics ; Inflammation ; }, abstract = {In multiple sclerosis (MS), alterations of the gut microbiota lead to inflammation. However, the role of other microbiomes in the body in MS has not been fully elucidated. In a pilot case-controlled study, we carried out simultaneous characterization of faecal and oral microbiota and conducted an in-depth analysis of bacterial alterations associated with MS. Using 16S rRNA sequencing and metabolic inference tools, we compared the oral/faecal microbiota and bacterial metabolism pathways in French MS patients (n = 14) and healthy volunteers (HV, n = 21). A classification model based on metabolite flux balance was established and validated in an independent German cohort (MS n = 12, HV n = 38). Our analysis revealed decreases in diversity indices and oral/faecal compartmentalization, the depletion of commensal bacteria (Aggregatibacter and Streptococcus in saliva and Coprobacter and Roseburia in faeces) and enrichment of inflammation-associated bacteria in MS patients (Leptotrichia and Fusobacterium in saliva and Enterobacteriaceae and Actinomyces in faeces). Several microbial pathways were also altered (the polyamine pathway and remodelling of bacterial surface antigens and energetic metabolism) while flux balance analysis revealed associated alterations in metabolite production in MS (nitrogen and nucleoside). Based on this analysis, we identified a specific oral metabolite signature in MS patients, that could discriminate MS patients from HV and rheumatoid arthritis patients. This signature allowed us to create and validate a discrimination model on an independent cohort, which reached a specificity of 92%. Overall, the oral and faecal microbiomes were altered in MS patients. This pilot study highlights the need to study the oral microbiota and oral health implications in patients with autoimmune diseases on a larger scale and suggests that knowledge of the salivary microbiome could help guide the identification of new pathogenic mechanisms associated with the microbiota in MS patients.}, }
@article {pmid38565558, year = {2024}, author = {Yang, H and Wu, X and Li, X and Zang, W and Zhou, Z and Zhou, Y and Cui, W and Kou, Y and Wang, L and Hu, A and Wu, L and Yin, Z and Chen, Q and Chen, Y and Huang, Z and Wang, Y and Gu, B}, title = {A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2842}, pmid = {38565558}, issn = {2041-1723}, support = {82072380//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81871734//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82102408//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2022M712681//China Postdoctoral Science Foundation/ ; }, mesh = {Animals ; Mice ; *Clostridioides difficile ; Arginine ; Ornithine ; Intestines/microbiology ; Fecal Microbiota Transplantation ; *Clostridium Infections/therapy/microbiology ; }, abstract = {Antibiotic-induced dysbiosis is a major risk factor for Clostridioides difficile infection (CDI), and fecal microbiota transplantation (FMT) is recommended for treating CDI. However, the underlying mechanisms remain unclear. Here, we show that Tritrichomonas musculis (T.mu), an integral member of the mouse gut commensal microbiota, reduces CDI-induced intestinal damage by inhibiting neutrophil recruitment and IL-1β secretion, while promoting Th1 cell differentiation and IFN-γ secretion, which in turn enhances goblet cell production and mucin secretion to protect the intestinal mucosa. T.mu can actively metabolize arginine, not only influencing the host's arginine-ornithine metabolic pathway, but also shaping the metabolic environment for the microbial community in the host's intestinal lumen. This leads to a relatively low ornithine state in the intestinal lumen in C. difficile-infected mice. These changes modulate C. difficile's virulence and the host intestinal immune response, and thus collectively alleviating CDI. These findings strongly suggest interactions between an intestinal commensal eukaryote, a pathogenic bacterium, and the host immune system via inter-related arginine-ornithine metabolism in the regulation of pathogenesis and provide further insights for treating CDI.}, }
@article {pmid38565398, year = {2024}, author = {Zhang, L and Yin, Z and Liu, X and Jin, G and Wang, Y and He, L and Li, M and Pang, X and Yan, B and Jia, Z and Ma, J and Wei, J and Cheng, F and Li, D and Wang, L and Han, Z and Liu, Q and Chen, F and Cao, H and Lei, P}, title = {Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline.}, journal = {Brain, behavior, and immunity}, volume = {119}, number = {}, pages = {171-187}, doi = {10.1016/j.bbi.2024.03.052}, pmid = {38565398}, issn = {1090-2139}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Polysorbates/pharmacology ; *Cognitive Dysfunction/metabolism/chemically induced ; *Emulsifying Agents/metabolism/pharmacology ; *Dysbiosis/metabolism ; *Blood-Brain Barrier/metabolism/drug effects ; Aging/metabolism ; Brain/metabolism/drug effects ; Male ; Microglia/metabolism/drug effects ; Brain-Gut Axis/drug effects ; Cognition/drug effects ; Bile Acids and Salts/metabolism ; }, abstract = {Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.}, }
@article {pmid38560650, year = {2024}, author = {Quan, YX and Lao, YD and Wu, HY and He, XX and Wu, LH}, title = {Beneficial effects of the first case of washed microbiota transplantation for postorgasmic illness syndrome: a case report.}, journal = {Sexual medicine}, volume = {12}, number = {2}, pages = {qfae015}, pmid = {38560650}, issn = {2050-1161}, abstract = {INTRODUCTION: Postorgasmic illness syndrome (POIS) is characterized by allergic symptoms and flu-like illness after ejaculation. There are still no effective treatments for POIS.<br><br>AIM: To report the first case of washed microbiota transplantation (WMT) to treat patient with POIS.<br><br>METHODS: Data were collected from a patient with POIS who had received 3 courses of WMT: self-rating scale of POIS symptoms, Self-rating Anxiety Scale, Self-rating Depression Scale, and Symptom Checklist 90. The patient's stool samples for 16sDNA sequencing were collected 1 month after WMT.<br><br>RESULTS: POIS symptoms improved after WMT. Scores decreased from baseline after WMT: self-rating scale of POIS symptoms (before WMT, 16; after first, 16; after second, 8; after third, 9), Self-rating Anxiety Scale (45, 42.5, 37.5, 45), Self-rating Depression Scale (63.75, 58.75, 47.5, 50), and Symptom Checklist 90 (143, 140, 109, 149). Characteristics of the patient's gut microbiota changed. At the genus level, the relative abundance of beneficial bacteria increased, and some opportunistic pathogenic bacteria decreased.<br><br>CONCLUSION: WMT may be an effective and safe choice for the treatment of patients with POIS by changing the gut microbiota of the host.}, }
@article {pmid38558912, year = {2024}, author = {Lee, KE and Tu, VY and Faye, AS}, title = {Optimal Management of Refractory Crohn's Disease: Current Landscape and Future Direction.}, journal = {Clinical and experimental gastroenterology}, volume = {17}, number = {}, pages = {75-86}, pmid = {38558912}, issn = {1178-7023}, abstract = {Refractory Crohn's disease, defined as ongoing inflammation despite the trial of multiple advanced therapies, impacts a number of individuals with Crohn's disease, and leads to significant burden in quality of life and cost. Interventions such as early implementation of advanced therapies, optimization of current therapies prior to switching to an alternative, as well as understanding the overlapping pathophysiology between immune-mediated disorders, however, can help shift the current landscape and reduce the number of patients with refractory disease. As such, in this review we summarize the key takeaways of the latest research in the management of moderate-to-severe Crohn's disease, focusing on maximization of our currently available medications, while also exploring topics such as combination advanced therapies. We also describe evidence for emerging and alternative therapeutic modalities, including fecal microbiota transplant, exclusive enteral feeding, hyperbaric oxygen, stem cell therapy, bone marrow transplant, and posaconazole, with a focus on both the potential impact and specific indications for each.}, }
@article {pmid38558090, year = {2024}, author = {Bolia, R and Goel, A and Thapar, N}, title = {Transanal irrigation in children with functional constipation: A systematic review and meta-analysis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {78}, number = {5}, pages = {1108-1115}, doi = {10.1002/jpn3.12200}, pmid = {38558090}, issn = {1536-4801}, support = {//None/ ; }, mesh = {Humans ; *Constipation/therapy ; Child ; *Therapeutic Irrigation/methods ; *Anal Canal/physiopathology ; Treatment Outcome ; }, abstract = {OBJECTIVES: Refractory functional constipation is a challenging condition to manage in children. The use of transanal irrigation (TAI) is well reported in children with neurological disorders as well as anorectal malformations but less so in children with functional disorders of defecation. The objective of our study was to evaluate the effectiveness, safety and outcomes of TAI in children with functional constipation.<br><br>METHODS: PubMed, Scopus and Google Scholar were searched for publications related to the use of TAI in functional constipation. Data regarding the study design, sample size, patient characteristics, investigator-reported response to TAI and adverse effects were extracted from studies that met the selection criteria. The inverse variance heterogeneity model was used for ascertaining the summary effect in this meta-analysis.<br><br>RESULTS: The search strategy yielded 279 articles of which five studies were included in the final review. The studies were from the United Kingdom (n&#x2009;=&#x2009;2), Netherlands (n&#x2009;=&#x2009;2) and Denmark (n&#x2009;=&#x2009;1). These studies included 192 children with a median age ranging from 7 to 12.2 years old. The TAI systems used in these studies were: Peristeen (n&#x2009;=&#x2009;2), Peristeen or Qufora (n&#x2009;=&#x2009;1), Alterna (n&#x2009;=&#x2009;1) and Navina (n&#x2009;=&#x2009;1). The follow-up duration ranged from 5.5 months to 3 years. Eleven (5.7%) children did not tolerate TAI and withdrew from treatment soon after initiation. The pooled investigator-reported success of TAI was 62% (95% CI: 52%-71%). The most common adverse event was pain which was experienced by 21.7% of children. A total of 27 (14%) were successfully weaned off TAI at the last follow-up.<br><br>CONCLUSIONS: TAI is reported to be successful in 62% of children with refractory functional constipation. There is a need for well-designed prospective trials to evaluate this treatment option in children with refractory functional constipation.}, }
@article {pmid38556088, year = {2024}, author = {Vega-Abellaneda, S and Dopazo, C and Yañez, F and Soler, Z and Xie, Z and Canalda-Baltrons, A and Pons-Tarín, M and Bilbao, I and Manichanh, C}, title = {Microbiome composition recovery after liver transplantation correlates with initial liver disease severity and antibiotics treatment.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {24}, number = {9}, pages = {1623-1633}, doi = {10.1016/j.ajt.2024.03.038}, pmid = {38556088}, issn = {1600-6143}, mesh = {Humans ; *Liver Transplantation/adverse effects ; Male ; Female ; *Gastrointestinal Microbiome/drug effects ; Middle Aged ; *Anti-Bacterial Agents/therapeutic use ; *End Stage Liver Disease/surgery ; Follow-Up Studies ; Prognosis ; Adult ; Feces/microbiology ; Dysbiosis/microbiology/etiology ; Severity of Illness Index ; Bacteria/isolation &amp; purification/genetics/classification ; Postoperative Complications/microbiology ; Case-Control Studies ; Graft Survival ; Aged ; Tissue Donors ; }, abstract = {Liver transplantation (LT) is crucial for end-stage liver disease, but it is linked to infection risks. Pathobionts, microorganisms potentially harmful under specific conditions, can cause complications posttransplant. Monitoring such pathogens in fecal samples can be challenging and therefore remains underexplored post-LT. This study aimed to analyze the gut microbiome before and after LT, tracking pathobionts and correlating clinical data. The study involved 17 liver transplant recipients, 17 healthy relatives (spouses), and 13 donors. Gut samples collected pretranplantation and posttransplantation underwent bacterial and fungal profiling through DNA sequencing. Quantitative polymerase chain reaction was used to assess microbial load. Statistical analyses included alpha and beta diversity measures, differential abundance analysis, and correlation tests between microbiome and clinical parameters. Microbiome analysis revealed dynamic changes in diversity posttransplant. Notably, high-severity patients showed persistent and greater dysbiosis during the first months post-LT compared with low-severity patients, partly due to an antibiotic treatment pre-LT. The analysis identified a higher proportion of pathogens such as Escherichia coli/Shigella flexneri in high-severity cases posttransplant. Furthermore, butyrate producers including Roseburia intestinalis, Anaerostipes hadrus, and Eubacterium coprostanoligenes were positively correlated with levels of albumin. This study offers valuable insights into post-LT microbiome changes, shedding light on the need for tailored prophylactic treatment post-LT.}, }
@article {pmid38555945, year = {2024}, author = {Tu, Y and Luo, L and Zhou, Q and Ni, J and Tang, Q}, title = {Fecal Microbiota Transplantation Repairs Radiation Enteritis Through Modulating the Gut Microbiota-Mediated Tryptophan Metabolism.}, journal = {Radiation research}, volume = {201}, number = {6}, pages = {572-585}, doi = {10.1667/RADE-23-00189.1}, pmid = {38555945}, issn = {1938-5404}, mesh = {Animals ; *Tryptophan/metabolism ; *Enteritis/therapy/metabolism/microbiology/etiology ; *Gastrointestinal Microbiome/radiation effects ; *Mice, Inbred C57BL ; Mice ; *Fecal Microbiota Transplantation ; Female ; Humans ; Radiation Injuries/therapy/metabolism/microbiology ; Male ; }, abstract = {Radiation enteritis is a common complication of abdominal and pelvic radiotherapy. Several previous studies showed that fecal microbiota transplantation (FMT) could alleviate radiation enteritis. In this study, we investigated the efficacy of FMT in alleviating radiation enteritis and explored the mechanisms by multi-omics approaches. Briefly, C57BL/6J mice were subjected to 9 Gy irradiation to the localized abdominal field, and randomized received FMT from healthy donor mice or saline. H&amp;E staining of harvested small intestine showed FMT decreased epithelial injury. Radiation-induced microbiota dysbiosis, characterized by a decrease in beneficial bacteria Lactobacillaceae and Lachnospiraceae, while these bacteria were restored by FMT. Fecal metabolomics analysis revealed that FMT modulated metabolic dysregulation. Two tryptophan pathway metabolites, indole-3-acetaldehyde and N-Acetyl-5-hydroxytryptamine were decreased after irradiation, whereas these metabolites showed a pronounced recovery in mice receiving FMT. Proteomics analysis of small intestine indicated that radiation enteritis triggered immune-inflammatory responses, which were potentially mitigated by FMT. In 21 patients receiving pelvic radiotherapy for cervical cancer, those who developed enteritis (n = 15) had higher abundance in Lachnospiraceae. Moreover, Indole-3-acetaldehyde was reduced after irradiation. These findings provide insights into the therapeutic effects of FMT in radiation enteritis and highlight Lachnospiraceae and the tryptophan metabolite, Indole-3-acetaldehyde may protect against radiation enteritis.}, }
@article {pmid38555499, year = {2024}, author = {Heston, SM and Young, RR and Jenkins, K and Martin, PL and Stokhuyzen, A and Ward, DV and Bhattarai, SK and Bucci, V and Arshad, M and Chao, NJ and Seed, PC and Kelly, MS}, title = {The effects of antibiotic exposures on the gut resistome during hematopoietic cell transplantation in children.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2333748}, pmid = {38555499}, issn = {1949-0984}, support = {K12 HD105253/HD/NICHD NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; T32 HG008955/HG/NHGRI NIH HHS/United States ; K23 AI135090/AI/NIAID NIH HHS/United States ; T32 HD094671/HD/NICHD NIH HHS/United States ; }, mesh = {Child ; Humans ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacteria/genetics ; Fluoroquinolones/pharmacology ; *Gastrointestinal Microbiome/genetics ; *Hematopoietic Stem Cell Transplantation ; }, abstract = {Antibiotic resistance is a global threat driven primarily by antibiotic use. We evaluated the effects of antibiotic exposures on the gut microbiomes and resistomes of children at high risk of colonization by antibiotic-resistant bacteria. We performed shotgun metagenomic sequencing of 691 serially collected fecal samples from 80 children (<18 years) undergoing hematopoietic cell transplantation. We evaluated the effects of aerobic (cefepime, vancomycin, fluoroquinolones, aminoglycosides, macrolides, and trimethoprim-sulfamethoxazole) and anaerobic (piperacillin-tazobactam, carbapenems, metronidazole, and clindamycin) antibiotic exposures on the diversity and composition of the gut microbiome and resistome. We identified 372 unique antibiotic resistance genes (ARGs); the most frequent ARGs identified encode resistance to tetracyclines (n = 88), beta-lactams (n = 84), and fluoroquinolones (n = 79). Both aerobic and anaerobic antibiotic exposures were associated with a decrease in the number of bacterial species (aerobic, β = 0.71, 95% CI: 0.64, 0.79; anaerobic, β = 0.66, 95% CI: 0.53, 0.82) and the number of unique ARGs (aerobic, β = 0.81, 95% CI: 0.74, 0.90; anaerobic, β = 0.73, 95% CI: 0.61, 0.88) within the gut metagenome. However, only antibiotic regimens that included anaerobic activity were associated with an increase in acquisition of new ARGs (anaerobic, β = 1.50; 95% CI: 1.12, 2.01) and an increase in the relative abundance of ARGs in the gut resistome (anaerobic, β = 1.62; 95% CI: 1.15, 2.27). Specific antibiotic exposures were associated with distinct changes in the number and abundance of ARGs for individual antibiotic classes. Our findings detail the impact of antibiotics on the gut microbiome and resistome and demonstrate that anaerobic antibiotics are particularly likely to promote acquisition and expansion of antibiotic-resistant bacteria.}, }
@article {pmid38555356, year = {2024}, author = {Dörner, PJ and Anandakumar, H and Röwekamp, I and Fiocca Vernengo, F and Millet Pascual-Leone, B and Krzanowski, M and Sellmaier, J and Brüning, U and Fritsche-Guenther, R and Pfannkuch, L and Kurth, F and Milek, M and Igbokwe, V and Löber, U and Gutbier, B and Holstein, M and Heinz, GA and Mashreghi, MF and Schulte, LN and Klatt, AB and Caesar, S and Wienhold, SM and Offermanns, S and Mack, M and Witzenrath, M and Jordan, S and Beule, D and Kirwan, JA and Forslund, SK and Wilck, N and Bartolomaeus, H and Heimesaat, MM and Opitz, B}, title = {Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2788}, pmid = {38555356}, issn = {2041-1723}, support = {OP 86/12-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; OP 86/13-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB-TR84 A5//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB 1449 B02//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB-TR84 A5//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Humans ; Mice ; Animals ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Monocytes ; *Anti-Infective Agents/pharmacology ; Klebsiella pneumoniae ; Lung ; }, abstract = {Hospital-acquired pneumonia (HAP) is associated with high mortality and costs, and frequently caused by multidrug-resistant (MDR) bacteria. Although prior antimicrobial therapy is a major risk factor for HAP, the underlying mechanism remains incompletely understood. Here, we demonstrate that antibiotic therapy in hospitalized patients is associated with decreased diversity of the gut microbiome and depletion of short-chain fatty acid (SCFA) producers. Infection experiments with mice transplanted with patient fecal material reveal that these antibiotic-induced microbiota perturbations impair pulmonary defense against MDR Klebsiella pneumoniae. This is dependent on inflammatory monocytes (IMs), whose fatty acid receptor (FFAR)2/3-controlled and phagolysosome-dependent antibacterial activity is compromized in mice transplanted with antibiotic-associated patient microbiota. Collectively, we characterize how clinically relevant antibiotics affect antimicrobial defense in the context of human microbiota, and reveal a critical impairment of IM´s antimicrobial activity. Our study provides additional arguments for the rational use of antibiotics and offers mechanistic insights for the development of novel prophylactic strategies to protect high-risk patients from HAP.}, }
@article {pmid38554422, year = {2024}, author = {Paraschiv, AC and Vacaras, V and Nistor, C and Vacaras, C and Nistor, DT and Vesa, SC and Ilut, S and Muresanu, DF}, title = {Dysbiosis in Multiple Sclerosis: Can Immunoglobulin Y Supplements Help?.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {33}, number = {1}, pages = {115-122}, doi = {10.15403/jgld-5241}, pmid = {38554422}, issn = {1842-1121}, mesh = {Humans ; *Multiple Sclerosis/therapy ; Dysbiosis/microbiology/therapy ; Dietary Supplements/adverse effects ; *Probiotics/therapeutic use ; Inflammation ; *Autoimmune Diseases ; *Immunoglobulins ; }, abstract = {The role of gut microbiota in autoimmune disorders like multiple sclerosis is gaining attention. Multiple sclerosis is characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Alterations in gut microbiota have been linked to multiple sclerosis development, with decreased beneficial bacteria and increased harmful species. The gut-brain axis is a complex interface influencing bidirectional interactions between the gut and the brain. Dysbiosis, an imbalance in gut microbiota, has been associated with autoimmune diseases. The influence of gut microbiota in multiple sclerosis is reversible, making it a potential therapeutic target. Probiotics, prebiotics, and fecal microbiota transplantation have shown promise in multiple sclerosis treatment, with positive effects on inflammation and immune regulation. Immunoglobulin Y (IgY) supplements derived from chicken egg yolk have potential as nutraceuticals or dietary supplements. IgY technology has been effective against various infections, and studies have highlighted its role in modulating gut microbiota and immune responses. Clinical trials using IgY supplements in multiple sclerosis are limited but have shown positive outcomes, including reduced symptoms, and altered immune responses. Future research directions involve understanding the mechanisms of IgY's interaction with gut microbiota, optimal dosage determination, and long-term safety assessments. Combining IgY therapy with other interventions and investigating correlations between microbiota changes and clinical outcomes are potential avenues for advancing multiple sclerosis treatment with IgY supplements.}, }
@article {pmid38550860, year = {2024}, author = {Zhu, X and Zhou, Z and Pan, X}, title = {Research reviews and prospects of gut microbiota in liver cirrhosis: a bibliometric analysis (2001-2023).}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1342356}, pmid = {38550860}, issn = {1664-302X}, abstract = {INTRODUCTION: The gut-liver axis has emerged as a focal point in chronic liver disorders, prompting more research into the role of the gut microbiota in liver cirrhosis. In individuals with liver cirrhosis, changes in the structure and function of the gut microbiota are closely tied to clinical prognosis. However, there is a scarcity of bibliometric evaluations conducted in this particular field.<br><br>METHODS: This study is aiming to conduct a complete analysis of the knowledge structure and centers pertaining to gut microbiota in liver cirrhosis using bibliometric methods. Publications on gut microbiota and liver cirrhosis from 2001 to 2023 are sourced from the Web of Science Core Collection. For the bibliometric analysis, we employ VOSviewer, CiteSpace, and the R package "bibliometrix".<br><br>RESULTS: Our study encompasses a comprehensive collection of 3109 articles originating from 96 countries, with notable contributions from leading nations such as the United States and China. The quantity of publications concerning the gut microbiota of liver cirrhosis rises annually. The University of California San Diego, Virginia Commonwealth University, Zhejiang University are the primary research institutions. World Journal of Gastroenterology publishes the most papers in this field, while hepatology is the most frequently co-cited journal. These publications come from a total of 15,965 authors, and the most prolific authors are Bajaj Jasmohan S., Schnabl Bernd and Gillevet Patrick M., while the most co-cited authors are Bajaj Jasmohan S., Younossi Zobair M., and Reiner Wiest. In addition, "dysbiosis", "gut microbiota", "intestinal barrier", "fecal microbiota transplantation", and "complement-system" are the primary keywords of research trends in recent years.<br><br>DISCUSSION: This study offering a comprehensive insight into the research dynamics surrounding gut microbiota in patients with liver cirrhosis. It delineates the current research frontiers and hotspots, serving as a valuable guide for scholars.}, }
@article {pmid38548771, year = {2024}, author = {Jiang, L and Ye, Y and Han, Y and Wang, Q and Lu, H and Li, J and Qian, W and Zeng, X and Zhang, Z and Zhao, Y and Shi, J and Luo, Y and Qiu, Y and Sun, J and Sheng, J and Huang, H and Qian, P}, title = {Microplastics dampen the self-renewal of hematopoietic stem cells by disrupting the gut microbiota-hypoxanthine-Wnt axis.}, journal = {Cell discovery}, volume = {10}, number = {1}, pages = {35}, pmid = {38548771}, issn = {2056-5968}, support = {82222003//National Natural Science Foundation of China (National Science Foundation of China)/ ; 92268117//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82370105//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82000149//National Natural Science Foundation of China (National Science Foundation of China)/ ; Z24H080001//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; LQ21H180006//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; 2021M702853//China Postdoctoral Science Foundation/ ; }, abstract = {Microplastics (MPs) are contaminants ubiquitously found in the global biosphere that enter the body through inhalation or ingestion, posing significant risks to human health. Recent studies emerge that MPs are present in the bone marrow and damage the hematopoietic system. However, it remains largely elusive about the specific mechanisms by which MPs affect hematopoietic stem cells (HSCs) and their clinical relevance in HSC transplantation (HSCT). Here, we established a long-term MPs intake mouse model and found that MPs caused severe damage to the hematopoietic system. Oral gavage administration of MPs or fecal transplantation of microbiota from MPs-treated mice markedly undermined the self-renewal and reconstitution capacities of HSCs. Mechanistically, MPs did not directly kill HSCs but disrupted gut structure and permeability, which eventually ameliorated the abundance of Rikenellaceae and hypoxanthine in the intestine and inactivated the HPRT-Wnt signaling in bone marrow HSCs. Furthermore, administration of Rikenellaceae or hypoxanthine in mice as well as treatment of WNT10A in the culture system substantially rescued the MPs-induced HSC defects. Finally, we validated in a cohort of human patients receiving allogenic HSCT from healthy donors, and revealed that the survival time of patients was negatively correlated with levels of MPs, while positively with the abundance of Rikenellaceae, and hypoxanthine in the HSC donors' feces and blood. Overall, our study unleashes the detrimental roles and mechanisms of MPs in HSCs, which provides potential strategies to prevent hematopoietic damage from MPs and serves as a fundamental critique for selecting suitable donors for HSCT in clinical practice.}, }
@article {pmid38548441, year = {2024}, author = {Singh, J and Ibrahim, B and Han, SH}, title = {Nontraditional Treatment of Hepatic Encephalopathy.}, journal = {Clinics in liver disease}, volume = {28}, number = {2}, pages = {297-315}, doi = {10.1016/j.cld.2024.01.007}, pmid = {38548441}, issn = {1557-8224}, mesh = {Humans ; *Hepatic Encephalopathy/therapy/drug therapy ; Gastrointestinal Agents/therapeutic use ; *Rifamycins/therapeutic use ; Rifaximin/therapeutic use ; Lactulose/therapeutic use ; }, abstract = {The pathophysiology of hepatic encephalopathy (HE) is complex, with hyperammonemia playing a central role in its development. Traditional therapies for HE have targeted ammonia and include medications such as lactulose and rifaximin. Although these agents are considered standard of care, nontraditional treatments seek to affect other factors in the pathogenesis of HE. Finally, procedural therapies include albumin dialysis, shunt closure, and the ultimate cure for HE, which is liver transplant. The treatments discussed provide alternative options for patients who have failed standard of care. However, more high-quality studies are needed to routinely recommend many of these agents.}, }
@article {pmid38548440, year = {2024}, author = {Khalessi, A and Pyrsopoulos, NT}, title = {Pharmacologic Management of Hepatic Encephalopathy.}, journal = {Clinics in liver disease}, volume = {28}, number = {2}, pages = {287-296}, doi = {10.1016/j.cld.2024.01.006}, pmid = {38548440}, issn = {1557-8224}, mesh = {Humans ; *Hepatic Encephalopathy/drug therapy ; Lactulose/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Polyethylene Glycols/therapeutic use ; Zinc/therapeutic use ; Gastrointestinal Agents/therapeutic use ; }, abstract = {Hepatic encephalopathy is a common cause of morbidity and mortality among patients with decompensated liver cirrhosis. In this article, we review the history, mechanism, and evidence for first-line pharmacologic therapies for hepatic encephalopathy including nonabsorbable disaccharides, antibiotics, and electrolyte management. We also review newer, second-line therapies including polyethylene glycol, albumin, branched-chain amino acids, probiotics and fecal microbiota transplant, zinc, and l-ornithine-l-aspartate.}, }
@article {pmid38547865, year = {2024}, author = {Yousefi, Y and Baines, KJ and Maleki Vareki, S}, title = {Microbiome bacterial influencers of host immunity and response to immunotherapy.}, journal = {Cell reports. Medicine}, volume = {5}, number = {4}, pages = {101487}, pmid = {38547865}, issn = {2666-3791}, mesh = {Humans ; Immunotherapy ; *Microbiota ; *Gastrointestinal Microbiome ; Bacteria ; *Neoplasms ; }, abstract = {The gut microbiota influences anti-tumor immunity and can induce or inhibit response to immune checkpoint inhibitors (ICIs). Therefore, microbiome features are being studied as predictive/prognostic biomarkers of patient response to ICIs, and microbiome-based interventions are attractive adjuvant treatments in combination with ICIs. Specific gut-resident bacteria can influence the effectiveness of immunotherapy; however, the mechanism of action on how these bacteria affect anti-tumor immunity and response to ICIs is not fully understood. Nevertheless, early bacterial-based therapeutic strategies have demonstrated that targeting the gut microbiome through various methods can enhance the effectiveness of ICIs, resulting in improved clinical responses in patients with a diverse range of cancers. Therefore, understanding the microbiota-driven mechanisms of response to immunotherapy can augment the success of these interventions, particularly in patients with treatment-refractory cancers.}, }
@article {pmid38546675, year = {2024}, author = {Pötgens, SA and Havelange, V and Lecop, S and Li, F and Neyrinck, AM and Bindels, F and Neveux, N and Demoulin, JB and Moors, I and Kerre, T and Maertens, J and Walter, J and Schoemans, H and Delzenne, NM and Bindels, LB}, title = {Gut microbiome alterations at acute myeloid leukemia diagnosis are associated with muscle weakness and anorexia.}, journal = {Haematologica}, volume = {109}, number = {10}, pages = {3194-3208}, pmid = {38546675}, issn = {1592-8721}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Leukemia, Myeloid, Acute/microbiology/diagnosis/complications ; Male ; *Muscle Weakness/diagnosis/microbiology/etiology ; Female ; Middle Aged ; *Anorexia/microbiology/etiology/diagnosis ; Aged ; Adult ; Prospective Studies ; Feces/microbiology ; Cross-Sectional Studies ; Metabolomics/methods ; Metabolome ; }, abstract = {The gut microbiota makes critical contributions to host homeostasis, and its role in the treatment of acute myeloid leukemia (AML) has attracted attention. We investigated whether the gut microbiome is affected by AML, and whether such changes are associated with hallmarks of cachexia. Biological samples and clinical data were collected from 30 antibiotic- free AML patients at diagnosis and matched volunteers (1:1) in a multicenter, cross-sectional, prospective study. The composition and functional potential of the fecal microbiota were analyzed using shotgun metagenomics. Fecal, blood, and urinary metabolomics analyses were performed. AML patients displayed muscle weakness, anorexia, signs of altered gut function, and glycemic disorders. The composition of the fecal microbiota differed between patients with AML and control subjects, with an increase in oral bacteria. Alterations in bacterial functions and fecal metabolome support an altered redox status in the gut microbiota, which may contribute to the altered redox status observed in patients with AML. Eubacterium eligens, reduced 3-fold in AML patients, was strongly correlated with muscle strength and citrulline, a marker of enterocyte mass and function. Blautia and Parabacteroides, increased in patients with AML, were correlated with anorexia. Several bacterial taxa and metabolites (e.g., Blautia, Prevotella, phenylacetate, and hippurate) previously associated with glycemic disorders were altered. Our work revealed important perturbations in the gut microbiome of AML patients at diagnosis, which are associated with muscle strength, altered redox status, and anorexia. These findings pave the way for future mechanistic work to explore the function and therapeutic potential of the bacteria identified in this study.}, }
@article {pmid38546138, year = {2024}, author = {Pettit, NN and Shaeer, KM and Chahine, EB}, title = {Live Biotherapeutic Products for the Prevention of Recurrent Clostridioides difficile Infection.}, journal = {The Annals of pharmacotherapy}, volume = {58}, number = {12}, pages = {1204-1217}, doi = {10.1177/10600280241239685}, pmid = {38546138}, issn = {1542-6270}, mesh = {Humans ; *Clostridium Infections/prevention &amp; control/drug therapy ; *Fecal Microbiota Transplantation/methods ; *Clostridioides difficile ; Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; Biological Products/administration &amp; dosage/therapeutic use ; Recurrence ; Secondary Prevention/methods ; Broadly Neutralizing Antibodies ; Antibodies, Monoclonal ; }, abstract = {OBJECTIVE: To review the efficacy, safety, and role of live biotherapeutic products (LBPs) in the prevention of recurrent Clostridioides difficile infection (rCDI).<br><br>DATA SOURCES: A literature search was performed using PubMed and Google Scholar (through February 2024) with search terms RBX2660, SER-109, and fecal microbiota. Other resources included abstracts presented at recent conferences, national clinical practice guidelines, and manufacturers' websites.<br><br>All relevant studies, trial updates, conference abstracts, and guidelines in the English language were included.<br><br>DATA SYNTHESIS: Two LBPs were recently approved by the Food and Drug Administration for the prevention of recurrence in adults following antibiotic treatment for rCDI. Fecal microbiota, live-jslm is administered rectally as a retention enema, whereas fecal microbiota spores, live-brpk is given orally after bowel preparation. Several phase 2 and phase 3 clinical trials have established the safety and efficacy of these LBPs in reducing rates of rCDI compared with placebo. Patients with severe immunosuppression and those with inflammatory bowel disease were largely excluded from these trials.<br><br>Live biotherapeutic products offer a similar mechanism to conventional fecal microbiota transplant (FMT) in preventing rCDI through microbiota restoration. The primary advantages of LBPs over FMT are their standardized composition and donor stool screening processes for transmissible pathogens. Bezlotoxumab is also available for the prevention of Clostridioides difficile infection; however, there are no clinical data available to compare the efficacy of LBPs with bezlotoxumab, and the benefit of simultaneous use of these preventative therapies is unclear.<br><br>CONCLUSIONS: Live biotherapeutic products provide a safe and effective option for the prevention of rCDI and represent an improvement over conventional FMT. Additional studies are needed to further determine their place in therapy relative to bezlotoxumab and in the setting of immunosuppression and inflammatory bowel disease.}, }
@article {pmid38545472, year = {2024}, author = {Patel, RK and Cardeiro, M and Frankel, L and Kim, E and Takabe, K and Rashid, OM}, title = {Incidence of Colorectal Cancer After Intestinal Infection Due to Clostridioides difficile.}, journal = {World journal of oncology}, volume = {15}, number = {2}, pages = {279-286}, pmid = {38545472}, issn = {1920-454X}, abstract = {BACKGROUND: Clostridioides difficile (C. difficile or C. diff) is a toxin-producing bacteria that is notorious for causing life-threatening diarrhea. Recent literature has investigated various effects of Clostridioides difficile infection (CDI) in cancer patients, but research into the impact of CDI on the development of cancer and its effects on the microbiome is limited. CDI predominately affects the colon, which urges consideration into the sequalae of infection. This study investigated the correlation between CDI and the incidence of colorectal carcinoma (CRC).<br><br>METHODS: A retrospective study (2010 - 2020) was conducted using a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. The International Classification of Disease ninth and 10th Codes (ICD-9, ICD-10), Current Procedural Terminology (CPT), and National Drug Codes were used to identify CRC diagnosis, CDI, and matching or control parameters. Patients were matched for age, sex, Charlson Comorbidity Index (CCI), region of residence, and CDI treatment. An additional, but separate, query was executed to include obese patients with and without CDI, who were similarly matched and assessed for CRC. Statistical analyses were implemented to assess significance and estimate odds ratios (ORs).<br><br>RESULTS: CDI was associated with a decreased incidence of CRC (OR = 0.59, 95% confidence interval (CI): 0.55 - 0.63), and the difference was statistically significant (P < 2.2 &#xd7; 10[-16]). CDI treatment, including appropriate antibiotics and fecal microbiota transplant (FMT), was controlled for in both infected and noninfected populations. Patients with a prior CDI who received relevant treatment were compared to patients with no history of CDI and received analogous treatment. Both populations subsequently developed CRC. Results remained statistically significant (P < 2.2 &#xd7; 10[-16]) with a relative risk (RR) of 0.57 (95% CI: 0.54 - 0.60). Obesity was explored as a controlled variable in relation to CRC development in patients with and without prior CDI. Obese patients without a history of CDI were found to have a decreased risk of developing CRC. Results were statistically significant (P < 4.3 &#xd7; 10[-13]) with an OR of 0.70 (95% CI: 0.63 - 0.77).<br><br>CONCLUSIONS: This study shows a statistically significant correlation between CDI and decreased incidence of CRC. Additionally, there is a statistically significant correlation between obese patients with CDI and an increased incidence of CRC. Further research is needed to explore the mechanism of this striking relationship and the implications of CDIs on the microbiome.}, }
@article {pmid38544906, year = {2024}, author = {Marshall, DA and MacDonald, KV and Kao, D and Bernstein, CN and Kaplan, GG and Jijon, H and Hazlewood, G and Panaccione, R and Nasser, Y and Raman, M and Moayyedi, P}, title = {Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation.}, journal = {Therapeutic advances in chronic disease}, volume = {15}, number = {}, pages = {20406223241239168}, pmid = {38544906}, issn = {2040-6223}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising treatment for active ulcerative colitis (UC). Understanding patient preferences can identify treatment features that may impact treatment decisions, improve shared decision-making, and contribute to patient-centered care, which is especially important in the context of novel treatments like FMT.<br><br>OBJECTIVES: We aimed to quantify preferences for active UC treatments, specifically FMT and biologics, and identify patient characteristics associated with different preference patterns.<br><br>DESIGN: This is a cross-sectional survey study.<br><br>METHODS: We administered a discrete choice experiment (DCE) survey to elicit preferences in a sample of Canadian adults with UC. DCE data were analyzed using a main-effects mixed logit model and used to predict uptake of hypothetical scenarios reflecting alternative combinations of treatment features. Latent class modeling identified heterogeneity in patient preference patterns.<br><br>RESULTS: Participants' (n&#x2009;=&#x2009;201) mean age was 47.1&#x2009;years (SD: 14.5&#x2009;years), 58% were female, and most (84%) had at least some post-secondary education. Almost half were willing to undergo FMT. When considering treatments for active UC, the most important attributes were chance of remission and severity of rare unknown side effects. All else equal, participants were most likely to uptake treatment that involves oral capsules/pills. Participants in the class with the highest utility for chance of remission were younger, had more severe disease, and 58% indicated that they would be willing to undergo FMT.<br><br>CONCLUSION: We identified characteristics of UC patients who are more likely to be interested in FMT using preference elicitation methods. Patient-centered care can be enhanced by knowing which patients are more likely to be interested in FMT, potentially improving satisfaction with and adherence to treatments for active UC to maximize the effectiveness of treatment while considering heterogeneity in patient preferences.}, }
@article {pmid38544348, year = {2024}, author = {Soukupova, H and Rehorova, V and Cibulkova, I and Duska, F}, title = {Assessment of Faecal Microbiota Transplant Stability in Deep-Freeze Conditions: A 12-Month Ex Vivo Viability Analysis.}, journal = {Journal of clinical laboratory analysis}, volume = {38}, number = {7}, pages = {e25023}, pmid = {38544348}, issn = {1098-2825}, support = {//Univerzita Karlova v Praze/ ; //Donatio Intensivistam Endowement Fund/ ; //FNKV University Hospital/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Feces/microbiology ; *Microbial Viability ; Freezing ; Cryopreservation/methods ; Male ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an established treatment for Clostridioides difficile infection and is under investigation for other conditions. The availability of suitable donors and the logistics of fresh stool preparation present challenges, making frozen, biobanked stools an attractive alternative.<br><br>AIMS: This study aimed to evaluate the long-term viability of bacterial populations in faecal samples stored at -80&#xb0;C for up to 12&#x2009;months, supporting the feasibility of using frozen grafts for FMT.<br><br>METHODS: Fifteen faecal samples from nine healthy donors were processed, mixed with cryoprotectants and stored at -80&#xb0;C. Samples were assessed at baseline and after 3, 6 and 12&#x2009;months using quantitative culturing methods to determine the concentration of live bacteria.<br><br>RESULTS: Quantitative analysis showed no significant decrease in bacterial viability over the 12-month period for both aerobic and anaerobic cultures (p&#x2009;=&#x2009;0.09). At all timepoints, the coefficients of variability in colony-forming unit (CFU) counts were greater between samples (102&#x2009;&#xb1;&#x2009;21% and 100&#x2009;&#xb1;&#x2009;13% for aerobic and anaerobic cultures, respectively) than the variability between measurements of the same sample (30&#x2009;&#xb1;&#x2009;22% and 30&#x2009;&#xb1;&#x2009;19%).<br><br>CONCLUSIONS: The study confirmed that faecal microbiota can be preserved with high viability in deep-freeze storage for up to a year, making allogenic FMT from biobanked samples a viable and safer option for patients. However, a multidonor approach may be beneficial to mitigate the risk of viability loss in any single donor sample.}, }
@article {pmid38543535, year = {2024}, author = {Yadav, D and Sainatham, C and Filippov, E and Kanagala, SG and Ishaq, SM and Jayakrishnan, T}, title = {Gut Microbiome-Colorectal Cancer Relationship.}, journal = {Microorganisms}, volume = {12}, number = {3}, pages = {}, pmid = {38543535}, issn = {2076-2607}, abstract = {Traditionally, the role of gut dysbiosis was thought to be limited to pathologies like Clostridioides difficile infection, but studies have shown its role in other intestinal and extraintestinal pathologies. Similarly, recent studies have surfaced showing the strong potential role of the gut microbiome in colorectal cancer, which was traditionally attributed mainly to sporadic or germline mutations. Given that it is the third most common cancer and the second most common cause of cancer-related mortality, 78 grants totaling more than USD 28 million have been granted to improve colon cancer management since 2019. Concerted efforts by several of these studies have identified specific bacterial consortia inducing a proinflammatory environment and promoting genotoxin production, causing the induction or progression of colorectal cancer. In addition, changes in the gut microbiome have also been shown to alter the response to cancer chemotherapy and immunotherapy, thus changing cancer prognosis. Certain bacteria have been identified as biomarkers to predict the efficacy of antineoplastic medications. Given these discoveries, efforts have been made to alter the gut microbiome to promote a favorable diversity to improve cancer progression and the response to therapy. In this review, we expand on the gut microbiome, its association with colorectal cancer, and antineoplastic medications. We also discuss the evolving paradigm of fecal microbiota transplantation in the context of colorectal cancer management.}, }
@article {pmid38542753, year = {2024}, author = {Shi, Y and Chen, J and Qu, D and Sun, Q and Yu, Y and Zhang, H and Liu, Z and Sha, J and Sun, Y}, title = {Ginsenoside Rg5 Activates the LKB1/AMPK/mTOR Signaling Pathway and Modifies the Gut Microbiota to Alleviate Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet.}, journal = {Nutrients}, volume = {16}, number = {6}, pages = {}, pmid = {38542753}, issn = {2072-6643}, support = {2023YFD1601600//National Key Research and Development Program/ ; 2023QN16//Jilin Provincial Department of Human Resources and Social Security/ ; 202301ZYTS352//Jilin Province Science and Technology Development Program/ ; }, mesh = {Humans ; Male ; Mice ; Animals ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; AMP-Activated Protein Kinases/metabolism ; *Ginsenosides/metabolism ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/metabolism ; Mice, Inbred C57BL ; Liver/metabolism ; Bacteria ; TOR Serine-Threonine Kinases/metabolism ; Signal Transduction ; }, abstract = {The primary objective of this investigation was to elucidate the manner in which ginsenoside Rg5 (Rg5) ameliorates nonalcoholic fatty liver disease (NAFLD) via the modulation of the gut microbiota milieu. We administered either a standard diet (ND) or a high-fat diet (HFD), coupled with 12-week treatment employing two distinct doses of Rg5 (50 and 100 mg/kg/d), to male C57BL/6J mice. In comparison to the HFD cohort, the Rg5-treated group demonstrated significant enhancements in biochemical parameters, exemplified by a substantial decrease in lipid concentrations, as well as the reduced expression of markers indicative of oxidative stress and liver injury. This signifies a mitigation of hepatic dysfunction induced by an HFD. Simultaneously, Rg5 demonstrates the capacity to activate the LKB1/AMPK/mTOR signaling pathway, instigating energy metabolism and consequently hindering the progression of NAFLD. Furthermore, we underscored the role of Rg5 in the treatment of NAFLD within the gut-microbiota-liver axis. Analysis via 16S rRNA sequencing unveiled that Rg5 intervention induced alterations in gut microbiota composition, fostering an increase in beneficial bacteria, such as Bacteroides and Akkermansia, while concurrently reducing the relative abundance of detrimental bacteria, exemplified by Olsenella. Furthermore, employing fecal microbiota transplantation (FMT) experiments, we observed analogous outcomes in mice subjected to fecal bacterial transplants, providing additional verification of the capacity of Rg5 to mitigate NAFLD in mice by actively participating in the restoration of gut microbiota via FMT. Drawing from these data, the regulation of the gut microbiota is recognized as an innovative strategy for treating or preventing NAFLD and metabolic syndrome. Consequently, these research findings suggest that Rg5 holds promise as a potential therapeutic agent for NAFLD management.}, }
@article {pmid38541242, year = {2024}, author = {Choi, SY and Choi, JH}, title = {Ovarian Cancer and the Microbiome: Connecting the Dots for Early Diagnosis and Therapeutic Innovations-A Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {3}, pages = {}, pmid = {38541242}, issn = {1648-9144}, support = {NRF-2017R1A5A2014768 and 2022R1A2C1003498//National Research Foundation of Korea/ ; }, mesh = {Female ; Humans ; Early Detection of Cancer ; *Ovarian Neoplasms/diagnosis/therapy ; *Microbiota ; }, abstract = {Ovarian cancer, which ranks eighth among global female cancers and fifth in fatality, poses a significant health challenge owing to its asymptomatic early stages. Understanding the pathogenesis requires extensive research. Recent studies have emphasized the role of the gut and cervicovaginal microbiota in ovarian cancer. This review explores the current understanding of the relationship between the microbiome and ovarian cancer, considering the potential of biomarkers in the serum and various tissues. Insights into the influence of the microbiome on treatments, including surgery and chemotherapy, open doors to innovative approaches, such as fecal microbiome transplantation. This synthesis of recent findings provides crucial insights into the intricate interplay between the microbiome and ovarian cancer, thereby shaping diagnostic and treatment strategies.}, }
@article {pmid38535842, year = {2024}, author = {Jessop, E and Li, L and Renaud, DL and Verbrugghe, A and Macnicol, J and Gamsjäger, L and Gomez, DE}, title = {Neonatal Calf Diarrhea and Gastrointestinal Microbiota: Etiologic Agents and Microbiota Manipulation for Treatment and Prevention of Diarrhea.}, journal = {Veterinary sciences}, volume = {11}, number = {3}, pages = {}, pmid = {38535842}, issn = {2306-7381}, abstract = {Neonatal calf diarrhea is the leading cause of neonatal morbidity and mortality globally. The changes associated with the gastrointestinal microbiota in neonatal calves experiencing diarrhea and its etiology are not fully understood or completely defined in the literature. Several studies have demonstrated that the fecal microbiota of calves that experience diarrhea substantially deviates from that of healthy age-matched calves. However, one key question remains: whether the changes observed in the bacterial communities (also known as dysbiosis) are a predisposing factor for, or the consequence of, gastrointestinal inflammation caused by the pathogens associated with calf diarrhea. The first objective of this literature review is to present the current information regarding the changes in the fecal microbiota of diarrheic calves and the impact of the pathogens associated with diarrhea on fecal microbiota. Modulation of the gastrointestinal microbiota using pre- and probiotics, colostrum feeding, and fecal microbiota transplantation (FMT) has been used to treat and prevent gastrointestinal diseases in humans and dogs. Although information regarding the use of probiotics for the prevention of diarrhea is available in cattle, little information is available regarding the use of these strategies for treating calf diarrhea and the use of prebiotics or FMT to prevent diarrhea. The second objective of this literature review is to summarize the current knowledge regarding the impact of prebiotics, probiotics, synbiotics, colostrum feeding, and FMT for the treatment and prevention of calf diarrhea.}, }
@article {pmid38535607, year = {2024}, author = {George, UE and Faleye, TOC and De Coninck, L and Agbaje, ST and Ifeorah, IM and Onoja, BA and Oni, EI and Olayinka, AO and Ajileye, TG and Oragwa, AO and Akinleye, TE and Popoola, BO and Osasona, OG and Olayinka, OT and George, OA and Muhammad, AI and Komolafe, I and Adeniji, AJ and Matthijnssens, J and Adewumi, MO}, title = {Metagenomic Detection and Genetic Characterization of Human Sapoviruses among Children with Acute Flaccid Paralysis in Nigeria.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {38535607}, issn = {2076-0817}, mesh = {Humans ; Nigeria/epidemiology ; *Sapovirus/genetics/isolation &amp; purification ; *Phylogeny ; *Genotype ; *Genome, Viral/genetics ; *Caliciviridae Infections/virology/epidemiology/diagnosis ; *Metagenomics ; Child ; Child, Preschool ; *Feces/virology ; Gastroenteritis/virology/epidemiology ; Genetic Variation/genetics ; Infant ; Male ; Female ; Paralysis/virology/epidemiology ; }, abstract = {Using a metagenomic sequencing approach on stool samples from children with Acute Flaccid Paralysis (AFP), we describe the genetic diversity of Sapoviruses (SaVs) in children in Nigeria. We identified six complete genome sequences and two partial genome sequences. Several SaV genogroups and genotypes were detected, including GII (GII.4 and GII.8), GIV (GIV.1), and GI (GI.2 and GI.7). To our knowledge, this is the first description of SaV infections and complete genomes from Nigeria. Pairwise identity and phylogenetic analysis showed that the Nigerian SaVs were related to previously documented gastroenteritis outbreaks with associated strains from China and Japan. Minor variations in the functional motifs of the nonstructural proteins NS3 and NS5 were seen in the Nigerian strains. To adequately understand the effect of such amino acid changes, a better understanding of the biological function of these proteins is vital. The identification of distinct SaVs reinforces the need for robust surveillance in acute gastroenteritis (AGE) and non-AGE cohorts to better understand SaVs genotype diversity, evolution, and its role in disease burden in Nigeria. Future studies in different populations are, therefore, recommended.}, }
@article {pmid38534216, year = {2024}, author = {Clarke, LM and Allegretti, JR}, title = {Review article: The epidemiology and management of Clostridioides difficile infection-A clinical update.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {59}, number = {11}, pages = {1335-1349}, doi = {10.1111/apt.17975}, pmid = {38534216}, issn = {1365-2036}, mesh = {Humans ; *Clostridium Infections/epidemiology/drug therapy/therapy/prevention &amp; control ; *Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Fecal Microbiota Transplantation ; Cross Infection/epidemiology/drug therapy/prevention &amp; control ; Fidaxomicin/therapeutic use ; Incidence ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Clostridioides difficile is the most common cause of healthcare-associated infection, and severe cases can result in significant complications. While anti-microbial therapy is central to infection management, adjunctive therapies may be utilised as preventative strategies.<br><br>AIM: This article aims to review updates in the epidemiology, diagnosis, and management, including treatment and prevention, of C. difficile infections.<br><br>METHODS: A narrative review was performed to evaluate the current literature between 1986 and 2023.<br><br>RESULTS: The incidence of C. difficile infection remains significantly high in both hospital and community settings, though with an overall decline in recent years and similar surveillance estimates globally. Vancomycin and fidaxomicin remain the first line antibiotics for treatment of non-severe C. difficile infection, though due to lower recurrence rates, infectious disease society guidelines now favour use of fidaxomicin. Faecal microbiota transplantation should still be considered to prevent recurrent C. difficile infection. However, in the past year the field has had a significant advancement with the approval of the first two live biotherapeutic products-faecal microbiota spores-live brpk, an oral capsule preparation, and faecal microbiota live-jslm-both indicated for the prevention of recurrent C. difficile infection, with additional therapies on the horizon.<br><br>CONCLUSION: Although the prevalence of C. difficile infection remains high, there have been significant advances in the development of novel therapeutics and preventative measures following changes in recent practice guidelines, and will continue to evolve in the future.}, }
@article {pmid38533674, year = {2024}, author = {Cui, J and Wang, S and Zhai, Z and Song, X and Qiu, T and Yu, L and Zhai, Q and Zhang, H}, title = {Induction of autism-related behavior in male mice by early-life vitamin D deficiency: association with disruption of the gut microbial composition and homeostasis.}, journal = {Food &amp; function}, volume = {15}, number = {8}, pages = {4338-4353}, doi = {10.1039/d4fo00279b}, pmid = {38533674}, issn = {2042-650X}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Vitamin D Deficiency/complications ; Mice ; Female ; Male ; Pregnancy ; *Autism Spectrum Disorder/microbiology/metabolism ; Homeostasis ; Mice, Inbred C57BL ; Disease Models, Animal ; Autistic Disorder/metabolism/microbiology ; Fecal Microbiota Transplantation ; Behavior, Animal ; Lactation ; Vitamin D/metabolism ; Prenatal Exposure Delayed Effects ; }, abstract = {Vitamin D deficiency (VDD) during early life emerges as a potential risk factor for autism spectrum disorder (ASD). Individuals with autism commonly exhibit lower vitamin D (VD) levels compared to the general population, and VD deficiency is prevalent during pregnancy and lactation. Moreover, gastrointestinal comorbidity, prevalent in ASD patients, correlates closely with disruptions in the gut microbiota and altered intestinal permeability. Therefore, it is fascinating and significant to explore the effects of maternal VD deficiency during pregnancy and lactation on the maturation of the gut microbiota of the offspring and its relevance to autism spectrum disorders. In this study, we established maternal pregnancy and lactation VD-deficient mouse models, employed shotgun macrogenomic sequencing to unveil alterations in the gut microbiome of offspring mice, and observed autism-related behaviours. Furthermore, fecal microbial transplantation (FMT) reversed repetitive and anxious behaviours and alleviated social deficits in offspring mice by modulating the gut microbiota and increasing short-chain fatty acid levels in the cecum, along with influencing the concentrations of claudin-1 and occludin in the colon. Our findings confirm that VDD during pregnancy and lactation is a risk factor for autism in the offspring, with disturbances in the structure and function of the offspring's gut microbiota contributing at least part of the effect. The study emphasises the importance of nutrition and gut health early in life. Simultaneously, this study further demonstrates the effect of VDD on ASD and provides potential ideas for early prevention and intervention of ASD.}, }
@article {pmid38532703, year = {2024}, author = {Sheikh, IA and Bianchi-Smak, J and Laubitz, D and Schiro, G and Midura-Kiela, MT and Besselsen, DG and Vedantam, G and Jarmakiewicz, S and Filip, R and Ghishan, FK and Gao, N and Kiela, PR}, title = {Transplant of microbiota from Crohn's disease patients to germ-free mice results in colitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2333483}, pmid = {38532703}, issn = {1949-0984}, support = {R01 DK136240/DK/NIDDK NIH HHS/United States ; R01 DK119198/DK/NIDDK NIH HHS/United States ; R01 AT010243/AT/NCCIH NIH HHS/United States ; R01 DK139790/DK/NIDDK NIH HHS/United States ; R01 DK132885/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; *Crohn Disease/microbiology ; *Clostridioides difficile ; *Gastrointestinal Microbiome ; *Colitis ; *Microbiota ; Fecal Microbiota Transplantation ; Dysbiosis/microbiology ; }, abstract = {Although the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically induced colitis. We aimed to further test the host response to fecal microbiome transplantation (FMT) from Crohn's disease patients on mucosal homeostasis in ex-germ-free (xGF) mice. We characterized and transferred fecal microbiota from healthy patients and patients with defined Crohn's ileocolitis (CD_L3) to germ-free mice and analyzed the resulting microbial and mucosal homeostasis by 16S profiling, shotgun metagenomics, histology, immunofluorescence (IF) and RNAseq analysis. We observed a markedly reduced engraftment of CD_L3 microbiome compared to healthy control microbiota. FMT from CD_L3 patients did not lead to ileitis but resulted in colitis with features consistent with CD: a discontinued pattern of colitis, more proximal colonic localization, enlarged isolated lymphoid follicles and/or tertiary lymphoid organ neogenesis, and a transcriptomic pattern consistent with epithelial reprograming and promotion of the Paneth cell-like signature in the proximal colon and immune dysregulation characteristic of CD. The observed inflammatory response was associated with persistently increased abundance of Ruminococcus gnavus, Erysipelatoclostridium ramosum, Faecalimonas umbilicate, Blautia hominis, Clostridium butyricum, and C. paraputrificum and unexpected growth of toxigenic C. difficile, which was below the detection level in the community used for inoculation. Our study provides the first evidence that the transfer of a dysbiotic community from CD patients can lead to spontaneous inflammatory changes in the colon of xGF mice and identifies a signature microbial community capable of promoting colonization of pathogenic and conditionally pathogenic bacteria.}, }
@article {pmid38532577, year = {2024}, author = {Chang, M and Chang, KT and Chang, F}, title = {Just a gut feeling: Faecal microbiota transplant for treatment of depression - A mini-review.}, journal = {Journal of psychopharmacology (Oxford, England)}, volume = {38}, number = {4}, pages = {353-361}, doi = {10.1177/02698811241240308}, pmid = {38532577}, issn = {1461-7285}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; *Depressive Disorder, Major/therapy/microbiology ; *Brain-Gut Axis/physiology ; Dysbiosis/therapy ; Animals ; Antidepressive Agents/therapeutic use ; }, abstract = {BACKGROUND: The microbiota-gut-brain axis (MGBA) allows bidirectional crosstalk between the brain and gut microbiota (GM) and is believed to contribute to regulating mood/cognition/behaviour/metabolism/health and homeostasis. Manipulation of GM through faecal microbiota transplant (FMT) is a new, exciting and promising treatment for major depressive disorder (MDD).<br><br>AIMS: This mini-review examines current research into GM and FMT as a therapy for depression.<br><br>METHODS: Original research articles published in Medline/Cochrane Library/PubMed/EMBASE/PsycINFO databases/National Institute of Health website Clinicaltrials.gov/controlled-trials.com were searched. Full articles included in reference lists were evaluated. We summarise current data on GM and depression and discuss communication through the MGBA and the interaction of antidepressants and GM through this. We review compositions of dysbiosis in depressed cohorts, focusing on future directions in the treatment of MDD.<br><br>RESULTS: Studies have demonstrated significant gut dysbiosis in depressed patients compared to healthy cohorts, with overgrowth of pro-inflammatory microbiota, reduction in anti-inflammatory species and reduced overall stability and taxonomic richness. FMT allows the introduction of healthy microbiota into the gastrointestinal tract, facilitating the restoration of eubiosis.<br><br>CONCLUSION: The GM plays an integral role in human health and disease through its communication with the rest of the body via the MGBA. FMT may provide a means to transfer the healthy phenotype into the recipient and this concept in humans is attracting enormous attention as a prospective treatment for psychopathologies, such as MDD, in the future. It may be possible to manipulate the GM in a number of ways, but further research is needed to determine the exact likelihood and profiles involved in the development and amelioration of MDD in humans, as well as the long-term effects and potential risks of this procedure.}, }
@article {pmid38531874, year = {2024}, author = {Luu, LDW and Pandey, A and Paramsothy, S and Ngo, C and Castaño-Rodríguez, N and Liu, C and Kamm, MA and Borody, TJ and Man, SM and Kaakoush, NO}, title = {Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2645}, pmid = {38531874}, issn = {2041-1723}, support = {APP2011047//Department of Health | National Health and Medical Research Council (NHMRC)/ ; APP2002686//Department of Health | National Health and Medical Research Council (NHMRC)/ ; IBD-0391R//Crohn&apos;s and Colitis Foundation (Crohn&apos;s &amp; Colitis Foundation)/ ; 988415//Crohn&apos;s and Colitis Foundation (Crohn&apos;s &amp; Colitis Foundation)/ ; }, mesh = {Animals ; Female ; Humans ; Mice ; *Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Feces ; GTP-Binding Proteins ; Intestinal Mucosa ; Treatment Outcome ; }, abstract = {Host molecular responses to fecal microbiota transplantation (FMT) in ulcerative colitis are not well understood. Here, we profile the human colonic mucosal transcriptome prior to and following FMT or placebo to identify molecules regulated during disease remission. FMT alters the transcriptome above the effect of placebo (n = 75 vs 3 genes, q < 0.05), including modulation of structural, metabolic and inflammatory pathways. This response is attributed to responders with no consistency observed in non-responders. Regulated pathways in responders include tight junctions, calcium signalling and xenobiotic metabolism. Genes significantly regulated longitudinally in responders post-FMT could discriminate them from responders and non-responders at baseline and non-responders post-FMT, with GBP5 and IRF4 downregulation being associated with remission. Female mice with a deletion of GBP5 are more resistant to developing colitis than their wild-type littermates, showing higher colonic IRF4 phosphorylation. The colonic mucosal response discriminates UC remission following FMT, with GBP5 playing a detrimental role in colitis.}, }
@article {pmid38531144, year = {2024}, author = {Yu, H and Yang, WM and Chen, YH and Guo, L and Li, R and Xue, F and Tan, QR and Peng, ZW}, title = {The gut microbiome from middle-aged women with depression modulates depressive-like behaviors and plasma fatty acid metabolism in female middle-aged mice.}, journal = {Journal of psychiatric research}, volume = {173}, number = {}, pages = {139-150}, doi = {10.1016/j.jpsychires.2024.03.023}, pmid = {38531144}, issn = {1879-1379}, mesh = {Middle Aged ; Mice ; Humans ; Female ; Animals ; Infant ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; Depression/therapy/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD).<br><br>OBJECTIVE: This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT).<br><br>METHODS: Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16&#xa0;S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated.<br><br>RESULTS: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, Butyricicoccus, and Blautia, demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC&#xa0;=&#xa0;0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice.<br><br>CONCLUSIONS: These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.}, }
@article {pmid38530358, year = {2024}, author = {Pal, S and Morgan, X and Dar, HY and Gacasan, CA and Patil, S and Stoica, A and Hu, YJ and Weitzmann, MN and Jones, RM and Pacifici, R}, title = {Gender-affirming hormone therapy preserves skeletal maturation in young mice via the gut microbiome.}, journal = {The Journal of clinical investigation}, volume = {134}, number = {10}, pages = {}, pmid = {38530358}, issn = {1558-8238}, support = {R01 DK112946/DK/NIDDK NIH HHS/United States ; S10 RR028009/RR/NCRR NIH HHS/United States ; U54 AG062334/AG/NIA NIH HHS/United States ; R01 HD115881/HD/NICHD NIH HHS/United States ; R01 AR079298/AR/NIAMS NIH HHS/United States ; R01 DK119229/DK/NIDDK NIH HHS/United States ; R01 DK124821/DK/NIDDK NIH HHS/United States ; I01 BX005852/BX/BLRD VA/United States ; R01 AR068157/AR/NIAMS NIH HHS/United States ; R01 AR070091/AR/NIAMS NIH HHS/United States ; I01 BX000105/BX/BLRD VA/United States ; R01 DK098391/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; Female ; Male ; *T-Lymphocytes, Regulatory/immunology/drug effects ; Bone Development/drug effects ; Osteogenesis/drug effects ; Bacteroides ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {Gender-affirming hormone therapy (GAHT) is often prescribed to transgender (TG) adolescents to alleviate gender dysphoria, but the effect of GAHT on the growing skeleton is unclear. We found GAHT to improve trabecular bone structure via increased bone formation in young male mice and not to affect trabecular structure in female mice. GAHT modified gut microbiome composition in both male and female mice. However, fecal microbiota transfers (FMTs) revealed that GAHT-shaped gut microbiome was a communicable regulator of bone structure and turnover in male, but not in female mice. Mediation analysis identified 2 species of Bacteroides as significant contributors to the skeletal effects of GAHT in male mice, with Bacteroides supplementation phenocopying the effects of GAHT on bone. Bacteroides have the capacity to expand Treg populations in the gut. Accordingly, GAHT expanded intestinal Tregs and stimulated their migration to the bone marrow (BM) in male but not in female mice. Attesting to the functional relevance of Tregs, pharmacological blockade of Treg expansion prevented GAHT-induced bone anabolism. In summary, in male mice GAHT stimulated bone formation and improved trabecular structure by promoting Treg expansion via a microbiome-mediated effect, while in female mice, GAHT neither improved nor impaired trabecular structure.}, }
@article {pmid38530054, year = {2024}, author = {Gurung, M and Schlegel, BT and Rajasundaram, D and Fox, R and Bode, L and Yao, T and Lindemann, SR and LeRoith, T and Read, QD and Simecka, C and Carroll, L and Andres, A and Yeruva, L}, title = {Microbiota from human infants consuming secretors or non-secretors mothers' milk impacts the gut and immune system in mice.}, journal = {mSystems}, volume = {9}, number = {4}, pages = {e0029424}, pmid = {38530054}, issn = {2379-5077}, support = {S10 OD028483/OD/NIH HHS/United States ; }, mesh = {Infant ; Female ; Humans ; Animals ; Mice ; *Immunity, Innate ; Mice, Inbred C57BL ; Lymphocytes/metabolism ; Milk, Human/chemistry ; *Microbiota ; Immune System/metabolism ; Oligosaccharides/analysis ; Bifidobacterium/genetics ; }, abstract = {UNLABELLED: Maternal secretor status is one of the determinants of human milk oligosaccharides (HMOs) composition, which, in turn, influences the gut microbiota composition of infants. To understand if this change in gut microbiota impacts immune cell composition, intestinal morphology, and gene expression, 21-day-old germ-free C57BL/6 mice were transplanted with fecal microbiota from infants whose mothers were either secretors (SMM) or non-secretors (NSM) or from infants consuming dairy-based formula (MFM). For each group, one set of mice was supplemented with HMOs. HMO supplementation did not significantly impact the microbiota diversity; however, SMM mice had a higher abundance of genus Bacteroides, Bifidobacterium, and Blautia, whereas, in the NSM group, there was a higher abundance of Akkermansia, Enterocloster, and Klebsiella. In MFM, gut microbiota was represented mainly by Parabacteroides, Ruminococcaceae_unclassified, and Clostrodium_sensu_stricto. In mesenteric lymph node, Foxp3+ T cells and innate lymphoid cells type 2 were increased in MFM mice supplemented with HMOs, while in the spleen, they were increased in SMM + HMOs mice. Similarly, serum immunoglobulin A was also elevated in MFM + HMOs group. Distinct global gene expression of the gut was observed in each microbiota group, which was enhanced with HMOs supplementation. Overall, our data show that distinct infant gut microbiota due to maternal secretor status or consumption of dairy-based formula and HMO supplementation impacts immune cell composition, antibody response, and intestinal gene expression in a mouse model.<br><br>IMPORTANCE: Early life factors like neonatal diet modulate gut microbiota, which is important for the optimal gut and immune function. One such factor, human milk oligosaccharides (HMOs), the composition of which is determined by maternal secretor status, has a profound effect on infant gut microbiota. However, how the infant gut microbiota composition determined by maternal secretor status or consumption of infant formula devoid of HMOs impacts infant intestinal ammorphology, gene expression, and immune signature is not well explored. This study provides insights into the differential establishment of infant microbiota derived from infants fed by secretor or non-secretor mothers milk or those consuming infant formula and demonstrates that the secretor status of mothers promotes Bifidobacteria and Bacteroides sps. establishment. This study also shows that supplementation of pooled HMOs in mice changed immune cell composition in the spleen and mesenteric lymph nodes and immunoglobulins in circulation. Hence, this study highlights that maternal secretor status has a role in infant gut microbiota composition, and this, in turn, can impact host gut and immune system.}, }
@article {pmid38529272, year = {2024}, author = {Yang, Y and Ma, Q and Wang, Q and Zhao, L and Liu, H and Chen, Y}, title = {Mannose enhances intestinal immune barrier function and dextran sulfate sodium salt-induced colitis in mice by regulating intestinal microbiota.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1365457}, pmid = {38529272}, issn = {1664-3224}, mesh = {Mice ; Humans ; Animals ; *Gastrointestinal Microbiome ; Mannose ; Dextran Sulfate/toxicity ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Occludin/genetics ; Quality of Life ; *Colitis/chemically induced/therapy/metabolism ; *Inflammatory Bowel Diseases ; Sodium Chloride ; Sodium Chloride, Dietary ; Body Weight ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) greatly affects human quality of life. Mannose has been reported to be used to treat IBD, but the mechanism is currently unknown.<br><br>METHODS: C57/BL mice were used as research subjects, and the mouse acute colitis model was induced using dextran sulfate sodium salt (DSS). After oral administration of mannose, the body weights and disease activity index (DAI) scores of the mice were observed. The colon lengths, histopathological sections, fecal content microbial sequencing, colon epithelial inflammatory genes, and tight junction protein Occludin-1 expression levels were measured. We further used the feces of mice that had been orally administered mannose to perform fecal bacterial transplantation on the mice with DSS-induced colitis and detected the colitis-related indicators.<br><br>RESULTS: Oral administration of mannose increased body weights and colon lengths and reduced DAI scores in mice with DSS-induced colitis. In addition, it reduced the expression of colon inflammatory genes and the levels of serum inflammatory factors (TNF-&#x3b1;, IL-6, and IL-1&#x3b2;), further enhancing the expression level of the colonic Occludin-1 protein and alleviating the toxic response of DSS to the intestinal epithelium of the mice. In addition, gut microbial sequencing revealed that mannose increased the abundance and diversity of intestinal flora. Additionally, after using the feces of the mannose-treated mice to perform fecal bacterial transplantation on the mice with DSS-induced colitis, they showed the same phenotype as the mannose-treated mice, and both of them alleviated the intestinal toxic reaction induced by the DSS. It also reduced the expression of intestinal inflammatory genes (TNF-&#x3b1;, IL-6, and IL-1&#x3b2;) and enhanced the expression level of the colonic Occludin-1 protein.<br><br>CONCLUSION: Mannose can treat DSS-induced colitis in mice, possibly by regulating intestinal microorganisms to enhance the intestinal immune barrier function and reduce the intestinal inflammatory response.}, }
@article {pmid38528541, year = {2024}, author = {Yu, F and Hu, X and Ren, H and Wang, X and Shi, R and Guo, J and Chang, J and Zhou, X and Jin, Y and Li, Y and Liu, Z and Hu, P}, title = {Protective effect of synbiotic combination of Lactobacillus plantarum SC-5 and olive oil extract tyrosol in a murine model of ulcerative colitis.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {308}, pmid = {38528541}, issn = {1479-5876}, support = {JLUXKJC2021ZY08//Interdisciplinary Integration and Innovation Project of JLU/ ; 419080520415//the Excellent Young Teachers Training Plan of Jilin University/ ; }, mesh = {Animals ; Mice ; *Colitis, Ulcerative/drug therapy ; *Lactobacillus plantarum ; Olive Oil ; NF-kappa B ; *Synbiotics ; Occludin ; Disease Models, Animal ; *Colitis/chemically induced ; Inflammation/complications/drug therapy ; Colon ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; *Inflammatory Bowel Diseases/drug therapy ; Dextran Sulfate/adverse effects ; Mice, Inbred C57BL ; Phenylethyl Alcohol/*analogs &amp; derivatives ; }, abstract = {BACKGROUND: Ulcerative colitisis (UC) classified as a form of inflammatory bowel diseases (IBD) characterized by chronic, nonspecific, and recurrent symptoms with a poor prognosis. Common clinical manifestations of UC include diarrhea, fecal bleeding, and abdominal pain. Even though anti-inflammatory drugs can help alleviate symptoms of IBD, their long-term use is limited due to potential side effects. Therefore, alternative approaches for the treatment and prevention of inflammation in UC are crucial.<br><br>METHODS: This study investigated the synergistic mechanism of Lactobacillus plantarum SC-5 (SC-5) and tyrosol (TY) combination (TS) in murine colitis, specifically exploring their regulatory activity on the dextran sulfate sodium (DSS)-induced inflammatory pathways (NF-&#x3ba;B and MAPK) and key molecular targets (tight junction protein). The effectiveness of 1&#xa0;week of treatment with SC-5, TY, or TS was evaluated in a DSS-induced colitis mice model by assessing colitis morbidity and colonic mucosal injury (n&#x2009;=&#x2009;9). To validate these findings, fecal microbiota transplantation (FMT) was performed by inoculating DSS-treated mice with the microbiota of TS-administered mice (n&#x2009;=&#x2009;9).<br><br>RESULTS: The results demonstrated that all three treatments effectively reduced colitis morbidity and protected against DSS-induced UC. The combination treatment, TS, exhibited inhibitory effects on the DSS-induced activation of mitogen-activated protein kinase (MAPK) and negatively regulated NF-&#x3ba;B. Furthermore, TS maintained the integrity of the tight junction (TJ) structure by regulating the expression of zona-occludin-1 (ZO-1), Occludin, and Claudin-3 (p&#x2009;<&#x2009;0.05). Analysis of the intestinal microbiota revealed significant differences, including a decrease in Proteus and an increase in Lactobacillus, Bifidobacterium, and Akkermansia, which supported the protective effect of TS (p&#x2009;<&#x2009;0.05). An increase in the number of Aspergillus bacteria can cause inflammation in the intestines and lead to the formation of ulcers. Bifidobacterium and Lactobacillus can regulate the micro-ecological balance of the intestinal tract, replenish normal physiological bacteria and inhibit harmful intestinal bacteria, which can alleviate the symptoms of UC. The relative abundance of Akkermansia has been shown to be negatively associated with IBD. The FMT group exhibited alleviated colitis, excellent anti-inflammatory effects, improved colonic barrier integrity, and enrichment of bacteria such as Akkermansia (p&#x2009;<&#x2009;0.05). These results further supported the gut microbiota-dependent mechanism of TS in ameliorating colonic inflammation.<br><br>CONCLUSION: In conclusion, the TS demonstrated a remission of colitis and amelioration of colonic inflammation in a gut microbiota-dependent manner. The findings suggest that TS could be a potential natural medicine for the protection of UC health. The above results suggest that TS can be used as a potential therapeutic agent for the clinical regulation of UC.}, }
@article {pmid38527650, year = {2024}, author = {Costa, DVS and Pham, N and Loureiro, AV and Yang, SE and Behm, BW and Warren, CA}, title = {Clostridioides difficile infection promotes gastrointestinal dysfunction in human and mice post-acute phase of the disease.}, journal = {Anaerobe}, volume = {87}, number = {}, pages = {102837}, pmid = {38527650}, issn = {1095-8274}, support = {R01 AI145322/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Clostridium Infections/microbiology/physiopathology ; Mice ; *Clostridioides difficile/pathogenicity ; *Mice, Inbred C57BL ; Female ; Male ; Middle Aged ; Disease Models, Animal ; Feces/microbiology ; Gastrointestinal Diseases/microbiology/physiopathology ; Aged ; Fecal Microbiota Transplantation ; Adult ; Peroxidase/metabolism ; }, abstract = {OBJECTIVES: In the US, Clostridioides difficile (C. difficile) infection (CDI) is the 8th leading cause of hospital readmission and 7th for mortality among all gastrointestinal (GI) disorders. Here, we investigated GI dysfunction post-CDI in humans and mice post-acute infection.<br><br>MATERIALS AND METHODS: From March 2020 to July 2021, we reviewed the clinical records of 67 patients referred to the UVA Complicated C. difficile clinic for fecal microbiota transplantation (FMT) eligibility. C57BL/6 mice were infected with C. difficile and clinical scores were determined daily. Stool samples from mice were collected to measure the shedding of C. difficile and myeloperoxidase (MPO) levels. On day 21 post-infection, Evans's blue and FITC-70kDa methods were performed to evaluate GI motility in mice.<br><br>RESULTS: Of the 67 patients evaluated at the C. difficile clinic, 40 patients (59.7%) were confirmed to have CDI, and 22 patients (32.8%) with post-CDI IBS (diarrhea-type, constipation-type, and mixed-type). In infected mice, levels of MPO in stools and clinical score were higher on day 3. On day 21, mice recovered from body weight loss induced by CDI, and fecal MPO was undetectable. The total GI transit time (TGITT) and FITC-70kDa levels on the proximal colon were increased in infected mice (p&#xa0;=&#xa0;0.002), suggesting a constipation phenotype post-acute phase of CDI. A positive correlation intestinal inflammation on day 3 and TGITT on day 21 was observed.<br><br>CONCLUSION: In conclusion, post-infection intestinal dysfunction occurs in humans and mice post-CDI. Importantly, we have validated in the mouse model that CDI causes abnormal GI transit in the recovery phase of the disease, indicating the potential utility of the model in exploring the underlying mechanisms of post-infectious IBS in humans.}, }
@article {pmid38527453, year = {2024}, author = {Maccauro, V and Fianchi, F and Gasbarrini, A and Ponziani, FR}, title = {Gut Microbiota in Primary Sclerosing Cholangitis: From Prognostic Role to Therapeutic Implications.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {42}, number = {4}, pages = {369-379}, doi = {10.1159/000538493}, pmid = {38527453}, issn = {1421-9875}, mesh = {Humans ; *Cholangitis, Sclerosing/microbiology/therapy/complications ; *Gastrointestinal Microbiome ; Prognosis ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Bile Acids and Salts/metabolism ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease of unknown etiology characterized by biliary inflammation and periductal fibrosis. The gut microbiota plays a crucial role in the pathogenesis of PSC by regulating bile acid metabolism, inflammation, and immune response. On the other hand, liver disease progression affects the composition of the gut microbiota, fostering these mechanisms in a mutual detrimental way.<br><br>SUMMARY: Recent evidences described a specific pro-inflammatory microbial signature in PSC patients, with an overall reduced bacterial diversity and the loss of beneficial metabolites such as short-chain fatty acids. As effective therapies for PSC are still lacking, targeting the gut microbiota offers a new perspective in the management of this disease. To date, antibiotics, fecal microbiota transplantation, and probiotics are the most studied gut microbiota-targeted intervention in PSC, but new potential strategies such as vaccines and bacteriophages represent possible future therapeutic horizons.<br><br>KEY MESSAGES: In this review, we focus on the role of the gut microbiota in PSC, considering its pathogenetic and prognostic role and the therapeutic implications.}, }
@article {pmid38527267, year = {2024}, author = {Fletcher, KA and Johnson, DB}, title = {Investigational Approaches for Treatment of Melanoma Patients Progressing After Standard of Care.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {30}, number = {2}, pages = {126-131}, doi = {10.1097/PPO.0000000000000702}, pmid = {38527267}, issn = {1540-336X}, mesh = {Humans ; *Melanoma/therapy ; Standard of Care ; Immunotherapy ; Proto-Oncogene Proteins B-raf ; }, abstract = {The advent of effective immunotherapy, specifically cytotoxic T-lymphocyte associated protein 4 and programmed cell death 1 inhibitors, as well as targeted therapy including BRAF/MEK inhibitors, has dramatically changed the prognosis for metastatic melanoma patients. Up to 50% of patients may experience long-term survival currently. Despite these advances in melanoma treatment, many patients still progress and die of their disease. As such, there are many studies aimed at providing new treatment options for this population. Therapies currently under investigation include, but are not limited to, novel immunotherapies, targeted therapies, tumor-infiltrating lymphocytes and other cellular therapies, oncolytic viral therapy and other injectables, and fecal microbiota transplant. In this review, we discuss the emerging treatment options for metastatic melanoma patients who have progressed on standard of care treatments.}, }
@article {pmid38524669, year = {2024}, author = {D'Amico, F and Rinaldi, M and Pascale, R and Fabbrini, M and Morelli, MC and Siniscalchi, A and Laici, C and Coladonato, S and Ravaioli, M and Cescon, M and Ambretti, S and Viale, P and Brigidi, P and Turroni, S and Giannella, M}, title = {Gut microbiome dynamics and Enterobacterales infection in liver transplant recipients: A prospective observational study.}, journal = {JHEP reports : innovation in hepatology}, volume = {6}, number = {4}, pages = {101039}, pmid = {38524669}, issn = {2589-5559}, abstract = {BACKGROUND &amp; AIMS: The aim of this study was to investigate gut microbiome (GM) dynamics in relation to carbapenem-resistant Enterobacterales (CRE) colonization, CRE infection, and non-CRE infection development within 2 months after liver transplant (LT).<br><br>METHODS: A single-center, prospective study was performed in patients undergoing LT from November 2018 to January 2020. The GM was profiled through 16S rRNA amplicon sequencing of a rectal swab taken on the day of transplantation, and fecal samples were collected weekly until 1 month after LT. A subset of samples was subjected to shotgun metagenomics, including resistome dynamics. The primary endpoint was to explore changes in the GM in the following groups: (1) CRE carriers developing CRE infection (CRE_I); (2) CRE carriers not developing infection (CRE_UI); (3) non-CRE carriers developing microbial infection (INF); and (4) non-CRE carriers not developing infection (NEG).<br><br>RESULTS: Overall, 97 patients were enrolled, and 91 provided fecal samples. Of these, five, nine, 22, and 55 patients were classified as CRE_I, CRE_UI, INF, and NEG, respectively. CRE_I patients showed an immediate and sustained post-LT decrease in alpha diversity, with depletion of the GM structure and gradual over-representation of Klebsiella and Enterococcus. The proportions of Klebsiella were significantly higher in CRE_I patients than in NEG patients even before LT, serving as an early marker of subsequent CRE infection. CRE_UI patients had a more stable and diverse GM, whose compositional dynamics tended to overlap with those of NEG patients.<br><br>CONCLUSIONS: GM profiling before LT could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.<br><br>IMPACT AND IMPLICATIONS: Little is known about the temporal dynamics of gut microbiome (GM) in liver transplant recipients associated with carbapenem-resistant Enterobacterales (CRE) colonization and infection. The GM structure and functionality of patients colonized with CRE and developing infection appeared to be distinct compared with CRE carriers without infection or patients with other microbial infection or no infection and CRE colonization. Higher proportions of antimicrobial-resistant pathogens and poor representation of bacteria and metabolic pathways capable of promoting overall host health were observed in CRE carriers who developed infection, even before liver transplant. Therefore, pretransplant GM profiling could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.}, }
@article {pmid38521337, year = {2024}, author = {Wan, L and Qian, C and Yang, C and Peng, S and Dong, G and Cheng, P and Zong, G and Han, H and Shao, M and Gong, G and Deng, Z and Pan, H and Wang, H and Liu, X and Wang, G and Lu, Y and Zhao, Y and Jiang, Z}, title = {Ginseng polysaccharides ameliorate ulcerative colitis via regulating gut microbiota and tryptophan metabolism.}, journal = {International journal of biological macromolecules}, volume = {265}, number = {Pt 2}, pages = {130822}, doi = {10.1016/j.ijbiomac.2024.130822}, pmid = {38521337}, issn = {1879-0003}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/drug therapy ; Tryptophan ; *Panax ; RNA, Ribosomal, 16S ; Cytokines ; Dextran Sulfate ; Disease Models, Animal ; Colon ; *Colitis ; Mice, Inbred C57BL ; }, abstract = {Ulcerative colitis (UC) is regarded as a recurring inflammatory disorder of the gastrointestinal tract, for which treatment approaches remain notably limited. In this study, we demonstrated that ginseng polysaccharides (GPs) could alleviate the development of dextran sulfate sodium (DSS)-induced UC as reflected by the ameliorated pathological lesions in the colon. GPs strikingly suppressed the expression levels of multiple inflammatory cytokines, as well as significantly inhibited the infiltration of inflammatory cells. Microbiota-dependent investigations by virtue of 16S rRNA gene sequencing, antibiotic treatment and fecal microbiota transplantation illustrated that GPs treatment prominently restored intestinal microbial balance predominantly through modulating the relative abundance of Lactobacillus. Additionally, GPs remarkably influenced the levels of microbial tryptophan metabolites, diminished the intestinal permeability and strengthened intestinal barrier integrity via inhibiting the 5-HT/HTR3A signaling pathway. Taken together, the promising therapeutic potential of GPs on the development of UC predominantly hinges on the capacity to suppress the expression of inflammatory cytokines as well as to influence Lactobacillus and microbial tryptophan metabolites.}, }
@article {pmid38521227, year = {2024}, author = {Moreau, GB and Naz, F and Petri, WA}, title = {Fecal microbiota transplantation stimulates type 2 and tolerogenic immune responses in a mouse model.}, journal = {Anaerobe}, volume = {86}, number = {}, pages = {102841}, pmid = {38521227}, issn = {1095-8274}, support = {R01 AI124214/AI/NIAID NIH HHS/United States ; R01 AI152477/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Mice ; *Disease Models, Animal ; *Clostridium Infections/therapy/immunology/microbiology ; Gastrointestinal Microbiome ; Dysbiosis/therapy ; Clostridioides difficile/immunology ; Immune Tolerance ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVES: Clostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. While previous work on fecal microbiota transplantation (FMT), a highly effective treatment for CDI, has focused on colonization resistance mounted against C. difficile by FMT-delivered commensals, the effects of FMT on host gene expression are relatively unexplored. This study aims to identify transcriptional changes associated with FMT, particularly changes associated with protective immune responses.<br><br>METHODS: Gene expression was assessed on day 2 and day 7 after FMT in mice after antibiotic-induced dysbiosis. Flow cytometry was also performed on colon and mesenteric lymph nodes at day 7 to investigate changes in immune cell populations.<br><br>RESULTS: FMT administration after antibiotic-induced dysbiosis successfully restored microbial alpha diversity to levels of donor mice by day 7 post-FMT. Bulk RNA sequencing of cecal tissue at day 2 identified immune genes, including both pro-inflammatory and Type 2 immune pathways as upregulated after FMT. RNA sequencing was repeated on day 7 post-FMT, and expression of these immune genes was decreased along with upregulation of genes associated with restoration of intestinal homeostasis. Immunoprofiling on day 7 identified increased colonic CD45[+] immune cells that exhibited dampened Type 1 and heightened regulatory and Type 2 responses. These include an increased abundance of eosinophils, alternatively activated macrophages, Th2, and T regulatory cell populations.<br><br>CONCLUSION: These results highlight the impact of FMT on host gene expression, providing evidence that FMT restores intestinal homeostasis after antibiotic treatment and facilitates tolerogenic and Type 2 immune responses.}, }
@article {pmid38519447, year = {2024}, author = {Stone, CB and Rudinsky, AJ and Urion, RJ and March, SB and Winston, JA}, title = {Gastrointestinal release site for delayed release and gelatin capsules in healthy dogs.}, journal = {Journal of veterinary pharmacology and therapeutics}, volume = {47}, number = {4}, pages = {266-273}, pmid = {38519447}, issn = {1365-2885}, support = {T35 OD010977/OD/NIH HHS/United States ; //T-35 grant (2T35OD010977)/ ; }, mesh = {Animals ; Dogs ; *Gelatin/administration &amp; dosage/chemistry ; *Delayed-Action Preparations ; *Capsules ; Male ; Female ; }, abstract = {Gelatin capsules deliver their contents to the stomach, while delayed-release (DR) capsules are designed to allow delivery to the small intestine. This study evaluated the gastrointestinal release site of DR capsules in six healthy adult dogs compared to gelatin capsules. Both gelatin and DR capsules were filled with barium-impregnated polyethylene spheres (BIPS™), and following enteral administration, release site was assessed using abdominal radiographs at baseline, immediately after ingestion, 15 min post-ingestion, 30 min post-ingestion, and then every 30 min thereafter. The evaluated phases included fasted conditions (phase 1, n = 6), increased meal size (phase 2, n = 2), double encapsulation (phase 3, n = 2), and altered capsule size (phase 4, n = 1). The released site was the stomach in all phases for both capsule types. In phase 1, DR capsules had a significantly prolonged time (median 60 min, range 60-90) to release BIPS™ compared to gelatin capsules (15 min, range 15-30; p = .03). In phase 2 (full meal size), 3 (double encapsulation), and 4 (smaller capsule size) pilot studies, release time was prolonged but still occurred in the stomach. This is similar to the release site for gelatin capsules but differs from the release site for DR capsules in people. This has implications for pharmacologic outcomes for products that are affected by gastric physiology (e.g. fecal microbiota transplantation). Based on this pilot data, clinicians and researchers should not assume DR capsules will allow for intestinal delivery of contents in dogs. Future studies should be conducted on larger and varied populations of dogs.}, }
@article {pmid38518650, year = {2024}, author = {Zhang, HJ and Fu, J and Yu, H and Xu, H and Hu, JC and Lu, JY and Bu, MM and Zhai, Z and Wang, JY and Ye, ML and Zuo, HT and Song, JY and Zhao, Y and Jiang, JD and Wang, Y}, title = {Berberine promotes the degradation of phenylacetic acid to prevent thrombosis by modulating gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {128}, number = {}, pages = {155517}, doi = {10.1016/j.phymed.2024.155517}, pmid = {38518650}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Berberine/pharmacology/analogs &amp; derivatives ; *Thrombosis/prevention &amp; control ; Male ; Mice ; *Phenylacetates/pharmacology ; Carrageenan ; Coptis/chemistry ; Disease Models, Animal ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Berberine is the main bioactive constituent of Coptis chinensis, a quaternary ammonium alkaloid. While berberine's cardiovascular benefits are well-documented, its impact on thrombosis remains not fully understood.<br><br>PURPOSE: This study investigates the potential of intestinal microbiota as a novel target for preventing thrombosis, with a focus on berberine, a natural compound known for its effectiveness in managing cardiovascular conditions.<br><br>METHODS: Intraperitoneal injection of carrageenan induces the secretion of chemical mediators such as histamine and serotonin from mast cells to promote thrombosis. This model can directly and visually observe the progression of thrombosis in a time-dependent manner. Thrombosis was induced by intravenous injection of 1 % carrageenan solution (20 mg/kg) to all mice except the vehicle control group. Quantitative analysis of gut microbiota metabolites through LC/MS. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of gut microbiota on thrombosis were explored by fecal microbiota transplantation.<br><br>RESULTS: Our research shows that berberine inhibits thrombosis by altering intestinal microbiota composition and related metabolites. Notably, berberine curtails the biosynthesis of phenylacetylglycine, a thrombosis-promoting coproduct of the host-intestinal microbiota, by promoting phenylacetic acid degradation. This research underscores the significance of phenylacetylglycine as a thrombosis-promoting risk factor, as evidenced by the ability of intraperitoneal phenylacetylglycine injection to reverse berberine's efficacy. Fecal microbiota transplantation experiment confirms the crucial role of intestinal microbiota in thrombus formation.<br><br>CONCLUSION: Initiating our investigation from the perspective of the gut microbiota, we have, for the first time, unveiled that berberine inhibits thrombus formation by promoting the degradation of phenylacetic acid, consequently suppressing the biosynthesis of PAG. This discovery further substantiates the intricate interplay between the gut microbiota and thrombosis. Our study advances the understanding that intestinal microbiota plays a crucial role in thrombosis development and highlights berberine-mediated intestinal microbiota modulation as a promising therapeutic approach for thrombosis prevention.}, }
@article {pmid38518435, year = {2024}, author = {Belotserkovsky, I and Stabryla, LM and Hunter, M and Allegretti, J and Callahan, BJ and Carlson, PE and Daschner, PJ and Goudarzi, M and Guyard, C and Jackson, SA and Rao, K and Servetas, SL and Sokol, H and Wargo, JA and Novick, S}, title = {Standards for fecal microbiota transplant: Tools and therapeutic advances.}, journal = {Biologicals : journal of the International Association of Biological Standardization}, volume = {86}, number = {}, pages = {101758}, doi = {10.1016/j.biologicals.2024.101758}, pmid = {38518435}, issn = {1095-8320}, mesh = {Humans ; Clostridioides difficile ; *Clostridium Infections/therapy/microbiology ; *Fecal Microbiota Transplantation/standards/methods ; Gastrointestinal Microbiome ; Congresses as Topic ; Practice Guidelines as Topic ; }, abstract = {Fecal microbiota transplantation (FMT) has been demonstrated to be efficacious in preventing recurrent Clostridioides difficile (C. difficile) infections, and is being investigated for treatment of several other diseases including inflammatory bowel disease, cancer, obesity, liver disease, and diabetes. To speed up the translation of FMT into clinical practice as a safe and standardized therapeutic intervention, additional evidence-based technical and regulatory guidance is needed. To this end in May of 2022, the International Alliance for Biological Standardization (IABS) and the BIOASTER Microbiology Technology Institute hosted a second webinar to discuss key issues still impeding the advancement and standardization of FMT. The goal of this two-day webinar was to provide a forum for scientific experts to share and discuss data and key challenges with one another. Discussion included a focus on the evaluation of safety, efficacy, clinical trial design, reproducibility and accuracy in obtained microbiome measurements and data reporting, and the potential for standardization across these areas. It also focused on increasing the application potential and visibility of FMT beyond treating C. difficile infections.}, }
@article {pmid38516869, year = {2024}, author = {Dong, S and Zeng, Q and He, W and Cheng, W and Zhang, L and Zhong, R and He, W and Fang, X and Wei, H}, title = {Effect of Lactobacillus plantarum BFS1243 on a female frailty model induced by fecal microbiota transplantation in germ-free mice.}, journal = {Food &amp; function}, volume = {15}, number = {8}, pages = {3993-4009}, doi = {10.1039/d3fo05282f}, pmid = {38516869}, issn = {2042-650X}, mesh = {Animals ; *Lactobacillus plantarum ; *Fecal Microbiota Transplantation ; Mice ; *Gastrointestinal Microbiome ; *Frailty/therapy/metabolism ; Female ; Humans ; *Germ-Free Life ; Probiotics/pharmacology ; Disease Models, Animal ; Mice, Inbred C57BL ; Aged ; Feces/microbiology ; }, abstract = {Frailty, a complex geriatric syndrome, significantly impedes the goal of achieving 'healthy aging'. Increasing evidence suggests a connection between gut microbiota, systemic inflammation, and disease. However, it remains to be determined whether interventions targeting the intestinal flora can effectively ameliorate frailty. Our research involved fecal microbiota transplantation (FMT) experiments on germ-free (GF) mice, dividing these mice into three groups: a group receiving transplants from healthy elderly individuals (HF group), a group of frailty patients (FF group), and the FF group supplemented with Lactobacillus plantarum BFS1243 (FFL group). Our findings indicated a significant shift in the gut microbiota of the FF group, in contrast to the HF group, characterized by decreased Akkermansia and increased Enterocloster, Parabacteroides, and Eisenbergiella. Concurrently, there was a reduction in amino acids and SCFAs, with BFS1243 partially mitigating these changes. The FF group exhibited an upregulation of inflammatory markers, including PGE2, CRP, and TNF-α, and a downregulation of irisin, all of which were moderated by BFS1243 treatment. Furthermore, BFS1243 improved intestinal barrier integrity and physical endurance in the FF mice. Correlation analysis revealed a negative association between SCFA-producing species and metabolites like lysine and butyric acid with pro-inflammatory factors. In conclusion, our study conclusively demonstrated that alterations in the gut microbiota of elderly individuals can lead to physical frailty, likely due to detrimental effects on the intestinal barrier and a pro-inflammatory state. These findings underscore the potential of gut microbiome modulation as a clinical strategy for treating frailty.}, }
@article {pmid38516478, year = {2024}, author = {Vidal-Gallardo, A and Méndez Benítez, JE and Flores Rios, L and Ochoa Meza, LF and Mata Pérez, RA and Martínez Romero, E and Vargas Beltran, AM and Beltran Hernandez, JL and Banegas, D and Perez, B and Martinez Ramirez, M}, title = {The Role of Gut Microbiome in the Pathogenesis and the Treatment of Inflammatory Bowel Diseases.}, journal = {Cureus}, volume = {16}, number = {2}, pages = {e54569}, pmid = {38516478}, issn = {2168-8184}, abstract = {Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic condition characterized by inflammation of the gastrointestinal tract. Its exact cause is unknown, but it's thought to result from a dysregulated immune response influenced by various factors, including changes in the intestinal microbiota, diet, lifestyle, and genetics. The gut microbiome, consisting of diverse microorganisms, plays a crucial role in maintaining physiological balance, with its disruption leading to inflammatory responses typical of IBD. Treatments primarily aim at symptom control, employing immunomodulators, corticosteroids, and newer approaches like probiotics, prebiotics, fecal transplants, and dietary modifications, all focusing on leveraging the microbiota's potential in disease management. These strategies aim to restore the delicate balance of the gut microbiome, typically altered in IBD, marked by a decrease in beneficial bacteria and an increase in harmful pathogens. This review underscores the importance of the gut microbiome in the pathogenesis and treatment of IBD, highlighting the shift towards personalized medicine and the necessity for further research in understanding the complex interactions between the gut microbiota, immune system, and genetics in IBD. It points to the potential of emerging treatments and the importance of a multifaceted approach in managing this complex and challenging disease.}, }
@article {pmid38516317, year = {2024}, author = {Caputi, V and Hill, L and Figueiredo, M and Popov, J and Hartung, E and Margolis, KG and Baskaran, K and Joharapurkar, P and Moshkovich, M and Pai, N}, title = {Functional contribution of the intestinal microbiome in autism spectrum disorder, attention deficit hyperactivity disorder, and Rett syndrome: a systematic review of pediatric and adult studies.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1341656}, pmid = {38516317}, issn = {1662-4548}, abstract = {INTRODUCTION: Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent studies have shown the presence of gut microbiota alterations in neurodevelopmental disorders. Here we performed a systematic review of alterations of the intestinal microbiota composition and function in pediatric and adult patients affected by autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome (RETT).<br><br>METHODS: We searched selected keywords in the online databases of PubMed, Cochrane, and OVID (January 1980 to December 2021) with secondary review of references of eligible articles. Two reviewers independently performed critical appraisals on the included articles using the Critical Appraisal Skills Program for each study design.<br><br>RESULTS: Our systematic review identified 18, 7, and 3 original articles describing intestinal microbiota profiles in ASD, ADHD, and RETT, respectively. Decreased Firmicutes and increased Bacteroidetes were observed in the gut microbiota of individuals affected by ASD and ADHD. Proinflammatory cytokines, short-chain fatty acids and neurotransmitter levels were altered in ASD and RETT. Constipation and visceral pain were related to changes in the gut microbiota in patients affected by ASD and RETT. Hyperactivity and impulsivity were negatively correlated with Faecalibacterium (phylum Firmicutes) and positively correlated with Bacteroides sp. (phylum Bacteroidetes) in ADHD subjects. Five studies explored microbiota-or diet-targeted interventions in ASD and ADHD. Probiotic treatments with Lactobacillus sp. and fecal microbiota transplantation from healthy donors reduced constipation and ameliorated ASD symptoms in affected children. Perinatal administration of Lactobacillus sp. prevented the onset of Asperger and ADHD symptoms in adolescence. Micronutrient supplementation improved disease symptomatology in ADHD without causing significant changes in microbiota communities' composition.<br><br>DISCUSSION: Several discrepancies were found among the included studies, primarily due to sample size, variations in dietary practices, and a high prevalence of functional gastrointestinal symptoms. Further studies employing longitudinal study designs, larger sample sizes and multi-omics technologies are warranted to identify the functional contribution of the intestinal microbiota in developmental trajectories of the human brain and neurobehavior.<br><br>https://clinicaltrials.gov/, CRD42020158734.}, }
@article {pmid38516241, year = {2024}, author = {Qiu, XX and Cheng, SL and Liu, YH and Li, Y and Zhang, R and Li, NN and Li, Z}, title = {Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease: Mechanism, clinical evidence, and prospect.}, journal = {World journal of gastroenterology}, volume = {30}, number = {8}, pages = {833-842}, pmid = {38516241}, issn = {2219-2840}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; *Non-alcoholic Fatty Liver Disease/therapy ; Randomized Controlled Trials as Topic ; }, abstract = {The population of non-alcoholic fatty liver disease (NAFLD) patients along with relevant advanced liver disease is projected to continue growing, because currently no medications are approved for treatment. Fecal microbiota transplantation (FMT) is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease. There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment, however, existing findings diverge on its effects. Herein, we briefly summarized the mechanism of FMT for NAFLD treatment, reviewed randomized controlled trials for evaluating its efficacy in NAFLD, and proposed the prospect of future trials on FMT.}, }
@article {pmid38513881, year = {2024}, author = {Xu, J and Lu, L and Jiang, S and Qin, Z and Huang, J and Huang, M and Jin, J}, title = {Paeoniflorin ameliorates oxaliplatin-induced peripheral neuropathy via inhibiting neuroinflammation through influence on gut microbiota.}, journal = {European journal of pharmacology}, volume = {971}, number = {}, pages = {176516}, doi = {10.1016/j.ejphar.2024.176516}, pmid = {38513881}, issn = {1879-0712}, mesh = {Humans ; Rats ; Animals ; Oxaliplatin/adverse effects ; *Antineoplastic Agents/therapeutic use ; *Gastrointestinal Microbiome ; Neuroinflammatory Diseases ; Toll-Like Receptor 4/metabolism ; NF-kappa B/metabolism ; Myeloid Differentiation Factor 88/metabolism ; *Peripheral Nervous System Diseases/chemically induced ; *Glucosides ; *Monoterpenes ; }, abstract = {Oxaliplatin (OXA)-induced peripheral neuropathy (OIPN) is a severe side effect that greatly limits OXA clinical use and threatens patients' life and health. Paeoniflorin exhibits extensive anti-inflammatory and neuroprotective effects, but whether it can protect against OIPN and the underlying mechanisms remain unclear. This study aimed to investigate the effects of paeoniflorin on OIPN and probe into the underlying mechanisms. The OIPN model was established through oxaliplatin injection in rats. The ameliorative effects of paeoniflorin on OIPN was assessed by nociceptive hypersensitivities through pain behavioral methods. Neuroinflammation were examined by measuring the levels of inflammatory cytokines and immune cells infiltration. The signaling pathway of TLR4/MyD88/NF-κB was evaluated by Western blotting. Gut microbial changes were detected by 16S rDNA sequencing technology. In addition, antibiotics-induced microbiota eradication and fecal microbial transplantation (FMT) were applied for exploring the function of gut microbiota in the protective effects of paeoniflorin. The results revealed that paeoniflorin significantly alleviated mechanical and cold hypersensitivity, mitigated neuroinflammation and influenced gut microbial composition in OIPN rats. Fecal microbiota transplantation further verified that gut microbiota was required for paeoniflorin ameliorating OIPN and that the underlying mechanism involved downregulation of TLR4/MyD88/NF-κB signaling. Specifically, Akkermansia, Dubosiella and Corynebacterium might serve as crucial genera regulated by paeoniflorin in the treatment of OIPN. In summary, our investigations delineate paeoniflorin's ameliorative effects on OIPN by alleviating neuroinflammation through regulations of gut microbiota. This suggests that paeoniflorin may serve as a new potential strategy for treatment of OIPN in clinical practice.}, }
@article {pmid38513836, year = {2024}, author = {Liu, D and Hu, L and Yang, Y and Wang, Y and Li, Y and Su, J and Wang, G and Gong, S}, title = {Saccharomyces boulardii alleviates allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.}, journal = {Immunology letters}, volume = {267}, number = {}, pages = {106853}, doi = {10.1016/j.imlet.2024.106853}, pmid = {38513836}, issn = {1879-0542}, mesh = {Animals ; *Asthma/therapy/metabolism/immunology/etiology/microbiology ; *Methyltransferases/metabolism/genetics ; *Gastrointestinal Microbiome/immunology ; Mice ; *Homeostasis ; *Adenosine/metabolism/analogs &amp; derivatives ; *Saccharomyces boulardii ; *Disease Models, Animal ; *Probiotics/administration &amp; dosage/therapeutic use ; *Up-Regulation ; Female ; Fecal Microbiota Transplantation ; Ovalbumin/immunology ; Mice, Inbred BALB C ; }, abstract = {BACKGROUND: Allergic asthma is a heterogeneous disease and new strategies are needed to prevent or treat this disease. Studies have shown that probiotic interventions are effective in preventing asthma. Here, we investigated the impact of Saccharomyces boulardii (S. boulardii) on ovalbumin (OVA)-induced allergic asthma in mice, as well as the underlying mechanisms.<br><br>METHODS: First, we constructed a mouse asthma model using OVA and given S. boulardii intervention. Next, we measured N6-methyladenosine (m6A) levels in lung injury tissues. 16 s rRNA was employed to identify different gut microbiota in fecal samples. The analysis of differential metabolites in feces was performed by non-targeted metabolomics. Pearson correlation coefficient was utilized to analyze correlation between gut microbiota, metabolites and methyltransferase-like 3 (METTL3). Finally, we collected mouse feces treated by OVA and S. boulardii intervention for fecal microbiota transplantation (FMT) and interfered with METTL3.<br><br>RESULTS: S. boulardii improved inflammation and oxidative stress and alleviated lung damage in asthmatic mice. In addition, S. boulardii regulated m6A modification levels in asthmatic mice. 16 s rRNA sequencing showed that S. boulardii remodeled gut microbiota homeostasis in asthmatic mice. Non-targeted metabolomics analysis showed S. boulardii restored metabolic homeostasis in asthmatic mice. There was a correlation between gut microbiota, differential metabolites, and METTL3 analyzed by Pearson correlation. Additionally, through FMT and interference of METTL3, we found that gut microbiota mediated the up-regulation of METTL3 by S. boulardii improved inflammation and oxidative stress in asthmatic mice, and alleviated lung injury.<br><br>CONCLUSIONS: S. boulardii alleviated allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.}, }
@article {pmid38513657, year = {2024}, author = {Zhu, X and Huang, X and Hu, M and Sun, R and Li, J and Wang, H and Pan, X and Ma, Y and Ning, L and Tong, T and Zhou, Y and Ding, J and Zhao, Y and Xuan, B and Fang, JY and Hong, J and Hon Wong, JW and Zhang, Y and Chen, H}, title = {A specific enterotype derived from gut microbiome of older individuals enables favorable responses to immune checkpoint blockade therapy.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {4}, pages = {489-505.e5}, doi = {10.1016/j.chom.2024.03.002}, pmid = {38513657}, issn = {1934-6069}, mesh = {Humans ; Animals ; Mice ; Aged ; *Gastrointestinal Microbiome ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Immunotherapy ; Aging ; CD3 Complex ; }, abstract = {Immunotherapy has revolutionized cancer treatment, but inconsistent responses persist. Our study delves into the intriguing phenomenon of enhanced immunotherapy sensitivity in older individuals with cancers. Through a meta-analysis encompassing 25 small-to-mid-sized trials of immune checkpoint blockade (ICB), we demonstrate that older individuals exhibit heightened responsiveness to ICB therapy. To understand the underlying mechanism, we reanalyze single-cell RNA sequencing (scRNA-seq) data from multiple studies and unveil distinct upregulation of exhausted and cytotoxic T cell markers within the tumor microenvironment (TME) of older patients. Recognizing the potential role of gut microbiota in modulating the efficacy of immunotherapy, we identify an aging-enriched enterotype linked to improved immunotherapy outcomes in older patients. Fecal microbiota transplantation experiments in mice confirm the therapeutic potential of the aging-enriched enterotype, enhancing treatment sensitivity and reshaping the TME. Our discoveries confront the prevailing paradox and provide encouraging paths for tailoring cancer immunotherapy strategies according to an individual's gut microbiome profile.}, }
@article {pmid38512763, year = {2024}, author = {Benedé-Ubieto, R and Cubero, FJ and Nevzorova, YA}, title = {Breaking the barriers: the role of gut homeostasis in Metabolic-Associated Steatotic Liver Disease (MASLD).}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2331460}, pmid = {38512763}, issn = {1949-0984}, mesh = {Humans ; *Insulin Resistance ; *Carcinoma, Hepatocellular ; Dysbiosis ; *Gastrointestinal Microbiome ; *Liver Neoplasms ; Inflammation ; Homeostasis ; }, abstract = {Obesity, insulin resistance (IR), and the gut microbiome intricately interplay in Metabolic-associated Steatotic Liver Disease (MASLD), previously known as Non-Alcoholic Fatty Liver Disease (NAFLD), a growing health concern. The complex progression of MASLD extends beyond the liver, driven by "gut-liver axis," where diet, genetics, and gut-liver interactions influence disease development. The pathophysiology of MASLD involves excessive liver fat accumulation, hepatocyte dysfunction, inflammation, and fibrosis, with subsequent risk of hepatocellular carcinoma (HCC). The gut, a tripartite barrier, with mechanical, immune, and microbial components, engages in a constant communication with the liver. Recent evidence links dysbiosis and disrupted barriers to systemic inflammation and disease progression. Toll-like receptors (TLRs) mediate immunological crosstalk between the gut and liver, recognizing microbial structures and triggering immune responses. The "multiple hit model" of MASLD development involves factors like fat accumulation, insulin resistance, gut dysbiosis, and genetics/environmental elements disrupting the gut-liver axis, leading to impaired intestinal barrier function and increased gut permeability. Clinical management strategies encompass dietary interventions, physical exercise, pharmacotherapy targeting bile acid (BA) metabolism, and microbiome modulation approaches through prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). This review underscores the complex interactions between diet, metabolism, microbiome, and their impact on MASLD pathophysiology and therapeutic prospects.}, }
@article {pmid38509104, year = {2024}, author = {Faraci, M and Bonaretti, C and Dell'Orso, G and Pierri, F and Giardino, S and Angiero, F and Blasi, S and Farronato, G and Di Marco, E and Trevisiol, A and Olcese, E and Rufino, L and Squillario, M and Biassoni, R}, title = {Association between oral and fecal microbiome dysbiosis and treatment complications in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {6708}, pmid = {38509104}, issn = {2045-2322}, mesh = {Humans ; Child ; *Mucositis/etiology ; Dysbiosis/etiology ; Prospective Studies ; *Microbiota ; *Graft vs Host Disease ; Bacteria ; *Hematopoietic Stem Cell Transplantation/adverse effects ; }, abstract = {The oral and gastrointestinal mucosae represent the main targets of the toxic effect of chemo and/or radiotherapy administered during the conditioning regimen before hematopoietic stem cell transplant (HSCT). These harmful consequences and the immunological complications that may occur after the transplant (such as Graft versus Host Disease, GvHD) are responsible for the clinical symptoms associated with mucositis during the aplasia phase, like pain, nausea, vomiting, and diarrhea. These toxicities could play a critical role in the oral and gastrointestinal microbiomes during the post-transplant phase, and the degree of microbial dysbiosis and dysregulation among different bacterial species could also be crucial in intestinal mucosa homeostasis, altering the host's innate and adaptive immune responses and favoring abnormal immune responses responsible for the occurrence of GvHD. This prospective pediatric study aims to analyze longitudinally oral and gut microbiomes in 17 pediatric patients who received allogeneic HSCT for malignant and non-malignant diseases. The oral mucositis was mainly associated with an increased relative abundance of Fusobacteria, and Prevotella species, while Streptococcus descendants showed a negative correlation. The fecal microbiome of subjects affected by cutaneous acute GvHD (aGvHD) correlated with Proteobacteria. Oral mucosal microbiota undergoes changes after HSCT, Fusobacteria, and Prevotella represent bacterial species associated with mucositis and they could be the target for future therapeutic approaches, while fecal microbiome in patients with acute GvHD (aGvHD) revealed an increase of different class of Proteobacteria (Alphaproteobacteria and Deltaproteobacteria) and a negative correlation with the class of Gammaproteobacteria.}, }
@article {pmid38509085, year = {2024}, author = {Fu, Y and Chen, YS and Xia, DY and Luo, XD and Luo, HT and Pan, J and Ma, WQ and Li, JZ and Mo, QY and Tu, Q and Li, MM and Zhao, Y and Li, Y and Huang, YT and Chen, ZX and Li, ZJ and Bernard, L and Dione, M and Zhang, YM and Miao, K and Chen, JY and Zhu, SS and Ren, J and Zhou, LJ and Jiang, XZ and Chen, J and Lin, ZP and Chen, JP and Ye, H and Cao, QY and Zhu, YW and Yang, L and Wang, X and Wang, WC}, title = {Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {25}, pmid = {38509085}, issn = {2055-5008}, mesh = {Humans ; *Lacticaseibacillus rhamnosus ; *Hyperuricemia/therapy ; Nucleosides ; Lactobacillus ; Proline ; Purines ; }, abstract = {Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.}, }
@article {pmid38508697, year = {2024}, author = {Knudsen, LA and Zachariassen, LS and Strube, ML and Havelund, JF and Pilecki, B and Nexoe, AB and Møller, FT and Sørensen, SB and Marcussen, N and Faergeman, NJ and Franke, A and Bang, C and Holmskov, U and Hansen, AK and Andersen, V}, title = {Assessment of the Inflammatory Effects of Gut Microbiota from Human Twins Discordant for Ulcerative Colitis on Germ-free Mice.}, journal = {Comparative medicine}, volume = {74}, number = {2}, pages = {55-69}, pmid = {38508697}, issn = {2769-819X}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/microbiology ; Humans ; Mice ; Female ; Germ-Free Life ; Dextran Sulfate/toxicity ; Feces/microbiology ; Pregnancy ; Male ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Disturbances in gut microbiota are prevalent in inflammatory bowel disease (IBD), which includes ulcerative colitis (UC). However, whether these disturbances contribute to development of the disease or are a result of the disease is unclear. In pairs of human twins discordant for IBD, the healthy twin has a higher risk of developing IBD and a gut microbiota that is more similar to that of IBD patients as compared with healthy individuals. Furthermore, appropriate medical treatment may mitigate these disturbances. To study the correlation between microbiota and IBD, we transferred stool samples from a discordant human twin pair: one twin being healthy and the other receiving treatment for UC. The stool samples were transferred from the disease-discordant twins to germ-free pregnant dams. Colitis was induced in the offspring using dextran sodium sulfate. As compared with offspring born to mice dams inoculated with stool from the healthy cotwin, offspring born to dams inoculated with stool from the UC-afflicted twin had a lower disease activity index, less gut inflammation, and a microbiota characterized by higher α diversity and a more antiinflammatory profile that included the presence and higher abundance of antiinflammatory species such as Akkermansia spp., Bacteroides spp., and Parabacteroides spp. These findings suggest that the microbiota from the healthy twin may have had greater inflammatory properties than did that of the twin undergoing UC treatment.}, }
@article {pmid38508446, year = {2025}, author = {Tao, S and Fan, J and Li, J and Wu, Z and Yao, Y and Wang, Z and Wu, Y and Liu, X and Xiao, Y and Wei, H}, title = {Extracellular vesicles derived from Lactobacillus johnsonii promote gut barrier homeostasis by enhancing M2 macrophage polarization.}, journal = {Journal of advanced research}, volume = {69}, number = {}, pages = {545-563}, pmid = {38508446}, issn = {2090-1224}, mesh = {Animals ; *Extracellular Vesicles/metabolism ; Mice ; *Gastrointestinal Microbiome ; *Macrophages/metabolism/immunology ; Swine ; Probiotics/pharmacology ; Fecal Microbiota Transplantation ; Homeostasis ; *Lactobacillus johnsonii/metabolism ; *Diarrhea/microbiology ; *Intestinal Mucosa/metabolism/microbiology ; Humans ; Macrophage Activation ; Germ-Free Life ; Disease Models, Animal ; }, abstract = {INTRODUCTION: Diarrheic disease is a common intestinal health problem worldwide, causing great suffering to humans and animals. Precise manipulation strategies based on probiotics to combat diarrheic diseases have not been fully developed.<br><br>OBJECTIVES: The aim of this study was to investigate the molecular mechanisms by which probiotics manipulate macrophage against diarrheic disease.<br><br>METHODS: Metagenome reveals gut microbiome profiles of healthy and diarrheic piglets. Fecal microbial transplantation (FMT) was employed to explore the causal relationship between gut microbes and diarrhea. The protective role of probiotics and their derived extracellular vesicles (EVs) was investigated in ETEC K88-infected mice. Macrophage depletion was performed to assess the role of macrophages in EVs against diarrhea. Execution of in vitro cell co-culture and transcriptome analyses elucidated the molecular mechanisms by which EVs modulate the macrophage and intestinal epithelial barrier.<br><br>RESULTS: Escherichia coli was enriched in weaned diarrheic piglets, while Lactobacillus johnsonii (L. john) showed a negative correlation with Escherichia coli. The transmission of diarrheic illness symptoms was achieved by transferring fecal microbiota, but not metabolites, from diarrheic pigs to germ-free (GF) mice. L. john's intervention prevented the transmission of disease phenotypes from diarrheic piglets to GF mice. L. john also reduces the gut inflammation induced by ETEC K88. The EVs secreted by L. john demonstrated enhanced efficacy in mitigating the adverse impacts induced by ETEC K88 through the modulation of macrophage phenotype. In vitro experiments have revealed that EVs activate M2 macrophages in a manner that shuts down ERK, thereby inhibiting NLRP3 activation in intestinal epithelial cells.<br><br>CONCLUSION: Our results reveal that intestinal microbiota drives the onset of diarrheic disease and that probiotic-derived EVs ameliorate diarrheic disease symptoms by modulating macrophage phenotypes. These findings can enhance the advancement of innovative therapeutic approaches for diarrheic conditions based on probiotic-derived EVs.}, }
@article {pmid38508330, year = {2024}, author = {Cymbal, M and Chatterjee, A and Baggott, B and Auron, M}, title = {Management of Clostridioides difficile Infection: Diagnosis, Treatment, and Future Perspectives.}, journal = {The American journal of medicine}, volume = {137}, number = {7}, pages = {571-576}, doi = {10.1016/j.amjmed.2024.03.024}, pmid = {38508330}, issn = {1555-7162}, mesh = {Humans ; *Clostridium Infections/diagnosis/therapy/drug therapy ; *Anti-Bacterial Agents/therapeutic use ; *Fecal Microbiota Transplantation ; Clostridioides difficile ; Antimicrobial Stewardship ; Vancomycin/therapeutic use ; Fidaxomicin/therapeutic use ; Broadly Neutralizing Antibodies ; Antibodies, Monoclonal ; }, abstract = {Clostridioides difficile infection is the most common healthcare-associated infection in the United States, with potential life-threatening complications and a significant impact on the costs of care. Antibiotic stewardship as well as discontinuation of chronic acid suppressive therapy are key for its prevention and treatment. Effective infection management requires appropriate interpretation of diagnostic tests, as well as the use of vancomycin and fidaxomicin as first-line treatment. Novel treatments such as Bezlotoxumab, fecal microbiota transplant, and live biotherapeutic products are proven effective in recurrent C. difficile infection and address dysbiosis.}, }
@article {pmid38506871, year = {2023}, author = {Rojo Gutiérrez, MI and Ballesteros González, D and Ortiz Durán, AK}, title = {[Non-IgE-mediated food allergy].}, journal = {Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993)}, volume = {70}, number = {4}, pages = {269-279}, doi = {10.29262/ram.v70i4.1338}, pmid = {38506871}, issn = {2448-9190}, mesh = {Adult ; Child ; Infant, Newborn ; Humans ; *Proctocolitis/etiology/therapy ; *Food Hypersensitivity/complications/therapy ; Food ; *Enterocolitis/etiology/therapy ; Inflammation ; }, abstract = {Food allergy is an immune response to proteins in food. It usually affects 8% of children and 2% of adults in Western countries. Non-IgE-mediated food allergy mainly affects the gastrointestinal tract. Gastrointestinal food allergies are classified, by their underlying pathogenesis, as: IgE-mediated, non-IgE-mediated, or mixed. The symptoms of patients with food protein-induced allergic proctocolitis originate from local inflammation of the distal colon, which causes hematochezia in neonates. It can affect the entire gastrointestinal tract and cause symptoms of intractable emesis, with subsequent metabolic disorders and hypovolemic shock. Food protein-induced enterocolitis syndrome is a non-IgE-mediated allergy that usually appears in childhood, with prolonged repetitive vomiting, starting 1 to 4 hours after ingestion of food. The manifestation in adults is usually triggered by the consumption of shellfish. Atopic diseases affect 40-60% of patients with food protein- induced enterocolitis syndrome, including 40-50% of those with food protein-induced enteropathy and proctocolitis. Probiotics (Lactobacillus GG) can alleviate the symptoms of allergic proctocolitis induced by food proteins, by altering the composition of the intestinal microbiota. Fecal microbiota transplantation (FMT) can change intestinal microecology efficiently compared to food or probiotics.}, }
@article {pmid38503933, year = {2024}, author = {Böttger, TW and Turina, M and Ensle, F and Mihic-Probst, D and Meier, CA and Ersözlü, S}, title = {Episodic Abdominal Pain-An Unexpected Cause for a Common Clinical Problem.}, journal = {Journal of general internal medicine}, volume = {39}, number = {9}, pages = {1751-1755}, pmid = {38503933}, issn = {1525-1497}, mesh = {Humans ; Male ; Middle Aged ; *Abdominal Pain/etiology ; Diverticulitis/complications/diagnosis ; Diagnosis, Differential ; }, abstract = {A previously healthy 55-year-old male patient presented repeatedly to the emergency department with severe episodic periumbilical abdominal pain. After an extensive diagnostic work-up and subsequent clinical deterioration, appendiceal diverticulitis was diagnosed. We identified a correlation of white blood cell counts and possibly faecal calprotectin with the clinical presentation. We suggest that appendiceal diverticulitis should be considered in middle-aged patients with recurrent episodes of abdominal pain that correlate with laboratory markers of inflammation.}, }
@article {pmid38502145, year = {2024}, author = {Xu, B and Fu, Y and Yin, N and Qin, W and Huang, Z and Xiao, W and Huang, H and Mei, Q and Fan, J and Zeng, Y and Huang, C}, title = {Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii served as key components of fecal microbiota transplantation to alleviate colitis.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {326}, number = {5}, pages = {G607-G621}, pmid = {38502145}, issn = {1522-1547}, support = {NO. 81970555//MOST | National Natural Science Foundation of China (NSFC)/ ; NO. 82270671//MOST | National Natural Science Foundation of China (NSFC)/ ; 22SJKGGG28//Songjiang Science and Technology Committee/ ; KY-2023-03-02//Shanghai Jiao Tong University School of Medicine, Digestive Institute/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Colitis/therapy/microbiology/chemically induced/immunology ; *Faecalibacterium prausnitzii ; Mice ; *Gastrointestinal Microbiome ; Male ; Humans ; *Bacteroides thetaiotaomicron ; Dextran Sulfate ; Mice, Inbred C57BL ; Interleukin-10/metabolism ; Adult ; Female ; Feces/microbiology ; Disease Models, Animal ; Middle Aged ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising therapy for inflammatory bowel disease (IBD) via rectifying gut microbiota. The aim of this study was to identify a mechanism of how specific bacteria-associated immune response contributes to alleviated colitis. Forty donors were divided into high (donor H) and low (donor L) groups according to the diversity and the abundance of Bacteroides and Faecalibacterium by 16S rRNA sequencing. FMT was performed on dextran sulfate sodium (DSS)-induced colitis in mice. Mice with colitis showed significant improvement in intestinal injury and immune imbalance after FMT with group donor H (P < 0.05). Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii were identified as targeted strains in donor feces by real-time PCR and droplet digital PCR. Mice with colitis were treated with mono- or dual-bacterial gavage therapy. Dual-bacterial therapy significantly ameliorated intestinal injury compared with mono-bacterial therapy (P < 0.05). Dual-bacterial therapy increased the M2/M1 macrophage polarization and improved the Th17/Treg imbalance and elevated IL-10 production by Tregs compared with the DSS group (P < 0.05). Metabolomics showed increased abundance of lecithin in the glycerophospholipid metabolism pathway. In conclusion, B. thetaiotaomicron and F. prausnitzii, as the key bacteria in donor feces, alleviate colitis in mice. The mechanism may involve increasing lecithin and regulating IL-10 production of intestinal Tregs.NEW &amp; NOTEWORTHY We demonstrate that donors with high abundance of Bacteroides and Faecalibacterium ameliorate dextran sulfate sodium (DSS)-induced colitis in mice by fecal microbiota transplantation (FMT). The combination therapy of Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii is superior to mono-bacterial therapy in ameliorating colitis in mice, of which mechanism may involve promoting lecithin and inducing IL-10 production of intestinal Tregs.}, }
@article {pmid38501942, year = {2024}, author = {Tan, Z and Wang, Z and Zeng, Q and Liu, X and Zhang, Y and Li, S and Huang, J and Zeng, Y and Huang, Z and Jin, C and Fu, N and Zhao, Q and Mu, Y and Wang, Z and Xiao, J and Yang, H and Ke, G}, title = {Natural intestinal metabolite xylitol reduces BRD4 levels to mitigate renal fibrosis.}, journal = {Clinical and translational science}, volume = {17}, number = {3}, pages = {e13770}, pmid = {38501942}, issn = {1752-8062}, support = {82060131//National Natural Science Foundation of China/ ; 82360154//National Natural Science Foundation of China/ ; 81871551//National Natural Science Foundation of China/ ; 2023A1515012474//Guangdong Basic and Applied Basic Research Foundation/ ; 2021YFS0159//Sichuan Science and Technology Program/ ; 2023A03J0344//Guangzhou City Science and Technology Project/ ; 2023A03J0342//Guangzhou City Science and Technology Project/ ; 202201020508//Guangzhou City Science and Technology Project/ ; }, mesh = {Humans ; *Nuclear Proteins ; Xylitol ; Molecular Docking Simulation ; Transcription Factors ; *Renal Insufficiency, Chronic/drug therapy ; Fibrosis ; Transforming Growth Factor beta ; Bromodomain Containing Proteins ; Cell Cycle Proteins ; }, abstract = {Renal fibrosis is a typical pathological change from chronic kidney disease (CKD) to end-stage renal failure, which presents significant challenges in prevention and treatment. The progression of renal fibrosis is closely associated with the "gut-kidney axis," therefore, although clinical intervention to modulate the "gut-kidney axis" imbalance associated with renal fibrosis brings hope for its treatment. In this study, we first identified the close relationship between renal fibrosis development and the intestinal microenvironment through fecal microtransplantation and non-absorbable antibiotics experiments. Then, we analyzed the specific connection between the intestinal microenvironment and renal fibrosis using microbiomics and metabolomics, screening for the differential intestinal metabolite. Potential metabolite action targets were initially identified through network simulation of molecular docking and further verified by molecular biology experiment. We used flow cytometry, TUNEL apoptosis staining, immunohistochemistry, and Western blotting to assess renal injury and fibrosis extent, exploring the potential role of gut microbial metabolite in renal fibrosis development. We discovered that CKD-triggered alterations in the intestinal microenvironment exacerbate renal injury and fibrosis. When metabolomic analysis was combined with experiments in vivo, we found that the differential metabolite xylitol delays renal injury and fibrosis development. We further validated this hypothesis at the cellular level. Mechanically, bromodomain-containing protein 4 (BRD4) protein exhibits strong binding with xylitol, and xylitol alleviates renal fibrosis by inhibiting BRD4 and its downstream transforming growth factor-β (TGF-β) pathway. In summary, our findings suggest that the natural intestinal metabolite xylitol mitigates renal fibrosis by inhibiting the BRD4-regulated TGF-β pathway.}, }
@article {pmid38501667, year = {2024}, author = {Allegretti, JR and Axelrad, J and Dalal, RS and Kelly, CR and Grinspan, A and Fischer, M}, title = {Outcomes After Fecal Microbiota Transplantation in Combination With Bezlotoxumab for Inflammatory Bowel Disease and Recurrent Clostridioides difficile Infection.}, journal = {The American journal of gastroenterology}, volume = {119}, number = {7}, pages = {1433-1436}, doi = {10.14309/ajg.0000000000002770}, pmid = {38501667}, issn = {1572-0241}, support = {//Merck/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; *Clostridium Infections/therapy ; *Broadly Neutralizing Antibodies/therapeutic use ; Adult ; Middle Aged ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Recurrence ; Treatment Outcome ; Combined Modality Therapy ; Clostridioides difficile ; Antibodies, Monoclonal/therapeutic use ; Colonoscopy ; }, abstract = {Fecal microbiota transplantation (FMT) prevents recurrent Clostridioides difficile infections (rCDI) in patients with inflammatory bowel disease. Bezlotoxumab is also indicated to prevent rCDI. We assess the impact of FMT in combination with bezlotoxumab in patients with inflammatory bowel disease and rCDI. We conducted a multicenter randomized placebo-controlled trial. All received a single colonoscopic FMT. Patients were randomized 1:1 to receive bezlotoxumab or placebo. Sixty-one patients were enrolled (30 received treatment and 31 received placebo). Overall, 5 participants (8%) experienced a CDI recurrence; 4 in the treatment arm, 1 in the placebo arm (13% vs 3%, P = 0.15). There was no clear benefit to the combination approach compared with FMT alone.}, }
@article {pmid38501427, year = {2024}, author = {Li, X and Liu, Y and Deng, K and Hu, Y}, title = {[Modulating gut microbiota improves neurological function and depressive symptoms in rats with post-stroke depression].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {44}, number = {2}, pages = {405-410}, pmid = {38501427}, issn = {1673-4254}, mesh = {Rats ; Animals ; *Depression/etiology/therapy/metabolism ; Rats, Sprague-Dawley ; Fluoxetine ; *Gastrointestinal Microbiome ; Occludin ; Anti-Bacterial Agents ; Water ; Sugars ; Immunoglobulin G ; *Methylamines ; }, abstract = {OBJECTIVE: To evaluate the effect of modulating gut microbiota for improving brain injury in rats with post-stroke depression.<br><br>METHODS: Adult SD rats were randomized into normal control, middle cerebral artery occlusion (MCAO), post-stroke depression (PSD), PSD with fecal transplantation, PSD with antibiotics (rifaximin), PSD with probiotics (lactobacilli), and PSD with fluoxetine treatment groups (n=9). Neurological function scores of the rats were determined, and the changes in sugar water preference and immobility time in forced swimming test were observed; plasma levels of trimethylamine N-oxide (TMAO) and hydrogen sulfide (H2S) were detected with ELISA, Occludin, and the expressions of occludin, caudin-5 and IgG proteins &#x2160; the brain tissues were determined using Western blotting.<br><br>RESULTS: Compared with those in the control group, the rats in MCAO and PSD groups had significantly increased neurological function scores, TMAO level, the ratio of TMAO/H2S, and immobility time in forced swimming test with a lowered level of H2S (P < 0.05). These changes were more obvious in PSD rats, which also exhibited a reduced sugar water preference with increased IgG protein and decreased occluding and caudin-5 expressions in the brain tissue (P < 0.05). TMAO/H2S ratio in PSD rats was positively correlated with neurological function score (R[2]=0.3235, P=0.0269) and immobility time in swimming (R[2]=0.6290, P=0.0004) and negatively with sugar water preference (R[2]=-0.4534, P=0.0059). Treatment with fecal transplantation, antibiotics, probiotics and fluoxetine all significantly reduced neurological function scores, immobility time in forced swimming, TMAO/H2S ratio, and IgG protein expression and increased sugar water preference and brain occludin and caudin-5 expressions of the PSD rats (P < 0.05).<br><br>CONCLUSION: In PSD rats, TMAO/H2S ratio is correlated with neurological function score, immobility time in forced swimming and sugar water preference, and modulating intestinal flora can improve neurological function and depressive symptoms and improve the integrity of the blood-brain barrier.}, }
@article {pmid38500273, year = {2024}, author = {Andriolo, IRL and Longo, B and de Melo, DM and de Souza, MM and Prediger, RD and da Silva, LM}, title = {Gastrointestinal Issues in Depression, Anxiety, and Neurodegenerative Diseases: A Systematic Review on Pathways and Clinical Targets Implications.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {23}, number = {11}, pages = {1371-1391}, pmid = {38500273}, issn = {1996-3181}, mesh = {Humans ; *Neurodegenerative Diseases ; *Depression/therapy ; *Gastrointestinal Diseases/therapy ; *Anxiety ; Gastrointestinal Microbiome/physiology ; Brain-Gut Axis/physiology ; Gastrointestinal Tract ; }, abstract = {INTRODUCTION: Multiple illnesses commonly involve both the Central Nervous System (CNS) and the Gastrointestinal Tract (GI) simultaneously. Consistent evidence suggests that neurological disorders impair GI tract function and worsen the symptomatology and pathophysiology of digestive disorders. On the other hand, it has been proposed that early functional changes in the GI tract contribute to the genesis of several CNS illnesses. Additionally, the role played by the gut in these diseases can be seen as a paradigm for how the gut and the brain interact.<br><br>METHODS: We mentioned significant GI symptoms and discussed how the GI tract affects central nervous system illnesses, including depression, anxiety, Alzheimer's disease, and Parkinson's disease in this study. We also explored potential pathophysiological underpinnings and novel targets for the creation of future therapies targeted at gut-brain connections.<br><br>RESULTS &amp; DISCUSSION: In this situation, modulating the gut microbiota through the administration of fecal microbiota transplants or probiotics may represent a new therapeutic option for this population, not only to treat GI problems but also behavioral problems, given the role that dysbiosis and leaky gut play in many neurological disorders.<br><br>CONCLUSION: Accurate diagnosis and treatment of co-existing illnesses also require coordination between psychiatrists, neurologists, gastroenterologists, and other specialties, as well as a thorough history and thorough physical examination.}, }
@article {pmid38499070, year = {2024}, author = {Baske, MM and Timmerman, KC and Garmo, LG and Freitas, MN and McCollum, KA and Ren, TY}, title = {Fecal microbiota transplant on Escherichia-Shigella gut composition and its potential role in the treatment of generalized anxiety disorder: A systematic review.}, journal = {Journal of affective disorders}, volume = {354}, number = {}, pages = {309-317}, doi = {10.1016/j.jad.2024.03.088}, pmid = {38499070}, issn = {1573-2517}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; *Anxiety Disorders/therapy/microbiology ; Brain-Gut Axis/physiology ; }, abstract = {BACKGROUND: The gut-brain-axis has a role in mental health disorders. In people with generalized anxiety disorder, GAD,[1] normal flora Escherichia-Shigella, are significantly elevated. Fecal microbiota transplant, FMT,[2] has been used to alter the gut composition in unhealthy individuals. There may be a role for FMT in the treatment of GAD to improve the gut-brain-axis.<br><br>METHODS: A systematic review of literature was conducted on articles published in PubMed, CINAHL Plus, Scopus, Cochrane Library, and Wed of Science from 2000 to 2022 that analyzed FMT as a modality to alter the gut microbiome in which Escherichia-Shigella levels were quantified and reported.<br><br>RESULTS: Of 1916 studies identified, 14 fit criteria and were included. Recipients undergoing FMT procedures had at least one enteric diagnosis and increased percentages of Escherichia-Shigella pre-FMT. Five studies on recurrent Clostridioides difficile infection, three irritable bowel syndrome, two ulcerative colitis, one ulcerative colitis and recurrent Clostridioides difficile infection, one acute intestinal and chronic graft-vs-host disease, one pouchitis, and one slow transit constipation. 10 articles (71.4&#xa0;%) showed decreased levels of Escherichia-Shigella post-FMT compared to pre-FMT. Four studies claimed the results were significant (40&#xa0;%).<br><br>LIMITATIONS: Limitations include potential bias in study selection, study methods of analysis, and generalization of results.<br><br>CONCLUSIONS: The gut-brain-axis has a role in GAD. Those with GAD have significantly higher Escherichia-Shigella compared to those without GAD. FMT has the potential to decrease Escherichia-Shigella in patients with GAD to positively alter the gut-brain-axis as a potential for future GAD treatment.}, }
@article {pmid38497338, year = {2024}, author = {Das, S and Preethi, B and Kushwaha, S and Shrivastava, R}, title = {Therapeutic strategies to modulate gut microbial health: Approaches for sarcopenia management.}, journal = {Histology and histopathology}, volume = {39}, number = {11}, pages = {1395-1425}, pmid = {38497338}, issn = {1699-5848}, mesh = {*Sarcopenia/therapy ; Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Dietary Supplements ; Muscle, Skeletal/metabolism ; Fecal Microbiota Transplantation ; Prebiotics ; Animals ; }, abstract = {Sarcopenia is a progressive and generalized loss of skeletal muscle and functions associated with ageing with currently no definitive treatment. Alterations in gut microbial composition have emerged as a significant contributor to the pathophysiology of multiple diseases. Recently, its association with muscle health has pointed to its potential role in mediating sarcopenia. The current review focuses on the association of gut microbiota and mediators of muscle health, connecting the dots between the influence of gut microbiota and their metabolites on biomarkers of sarcopenia. It further delineates the mechanism by which the gut microbiota affects muscle health with progressing age, aiding the formulation of a multi-modal treatment plan involving nutritional supplements and pharmacological interventions along with lifestyle changes compiled in the review. Nutritional supplements containing proteins, vitamin D, omega-3 fatty acids, creatine, curcumin, kefir, and ursolic acid positively impact the gut microbiome. Dietary fibres foster a conducive environment for the growth of beneficial microbes such as Bifidobacterium, Faecalibacterium, Ruminococcus, and Lactobacillus. Probiotics and prebiotics act by protecting against reactive oxygen species (ROS) and inflammatory cytokines. They also increase the production of gut microbiota metabolites like short-chain fatty acids (SCFAs), which aid in improving muscle health. Foods rich in polyphenols are anti-inflammatory and have an antioxidant effect, contributing to a healthier gut. Pharmacological interventions like faecal microbiota transplantation (FMT), non-steroidal anti-inflammatory drugs (NSAIDs), ghrelin mimetics, angiotensin-converting enzyme inhibitors (ACEIs), and butyrate precursors lead to the production of anti-inflammatory fatty acids and regulate appetite, gut motility, and microbial impact on gut health. Further research is warranted to deepen our understanding of the interaction between gut microbiota and muscle health for developing therapeutic strategies for ameliorating sarcopenic muscle loss.}, }
@article {pmid38496183, year = {2024}, author = {Basra, M and Patel, H and Stern-Harbutte, A and Lee, D and Gregg, RK and Waters, HB and Potter, AK}, title = {A Narrative Review on the Viability of Osteopathic Manipulative Medicine in Treating Irritable Bowel Syndrome With Constipation (IBS-C).}, journal = {Cureus}, volume = {16}, number = {2}, pages = {e54180}, pmid = {38496183}, issn = {2168-8184}, abstract = {Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal pain and alterations in bowel habits, with global prevalence. The etiology of the disease is likely multifactorial; however, autonomic nervous system (ANS) dysfunction and immune-mediated inflammation may contribute the most to the hallmark symptoms of abdominal pain and altered motility of the gut. Current pharmacological therapies operate to modulate intestinal transit, alter the composition of the gut flora and control pain. Non-pharmacological approaches include dietary changes, increased physical activity, or fecal microbiota transplants. None of these therapies can modulate ANS dysfunction or impact the underlying inflammation that is likely perpetuating the symptoms of IBS. Osteopathic Manipulative Medicine (OMM) is a clinical approach focused on physical manipulation of the body's soft tissues to correct somatic dysfunctions. OMM can directly target the pathophysiology of IBS through many approaches such as ANS modulation and lymphatic techniques to modify the inflammatory mechanisms within the body. Particular OMM techniques of use are lymphatic manipulation, myofascial release, sympathetic ganglia treatment, sacral rocking, counterstrain, and viscerosomatic treatment. The aim of this study is to identify OMM treatments that can be used to potentially reduce the inflammation and ANS dysfunction associated with IBS symptoms, thereby providing a new non-pharmacological targeted approach for treating the disease.}, }
@article {pmid38495755, year = {2024}, author = {Zou, X and Zou, G and Zou, X and Wang, K and Chen, Z}, title = {Gut microbiota and its metabolites in Alzheimer's disease: from pathogenesis to treatment.}, journal = {PeerJ}, volume = {12}, number = {}, pages = {e17061}, pmid = {38495755}, issn = {2167-8359}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Alzheimer Disease/therapy ; *Microbiota ; Brain-Gut Axis ; Brain ; }, abstract = {INTRODUCTION: An increasing number of studies have demonstrated that altered microbial diversity and function (such as metabolites), or ecological disorders, regulate bowel-brain axis involvement in the pathophysiologic processes in Alzheimer's disease (AD). The dysregulation of microbes and their metabolites can be a double-edged sword in AD, presenting the possibility of microbiome-based treatment options. This review describes the link between ecological imbalances and AD, the interactions between AD treatment modalities and the microbiota, and the potential of interventions such as prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and dietary interventions as complementary therapeutic strategies targeting AD pathogenesis and progression.<br><br>SURVEY METHODOLOGY: Articles from PubMed and china.com on intestinal flora and AD were summarized to analyze the data and conclusions carefully to ensure the comprehensiveness, completeness, and accuracy of this review.<br><br>CONCLUSIONS: Regulating the gut flora ecological balance upregulates neurotrophic factor expression, regulates the microbiota-gut-brain (MGB) axis, and suppresses the inflammatory responses. Based on emerging research, this review explored novel directions for future AD research and clinical interventions, injecting new vitality into microbiota research development.}, }
@article {pmid38495146, year = {2024}, author = {Xue, Y and Zhang, YN and Wang, M and Fu, HY and Mao, YC and Hu, M and Sun, MT and Guo, HG and Cao, L and Feng, CZ}, title = {Prolonged oral intake of green tea polyphenols attenuates delirium-like behaviors in mice induced by anesthesia/surgery.}, journal = {Heliyon}, volume = {10}, number = {5}, pages = {e26200}, pmid = {38495146}, issn = {2405-8440}, abstract = {Postoperative delirium (POD) is a severe postoperative complication characterized by delirium-like symptoms. So far, no effective preventable strategy for POD prevention has been identified. Reports show that the consumption of green tea polyphenols (GTP) is associated with better cognitive function by modulating the composition of gut microbiota. Whether GTP also play a role in alleviating POD through gut microbiota is unknown. Herein, we studied the effect of prolonged (eight weeks) GTP intake on postoperative delirium in C57BL/6 mice with laparotomies under isoflurane anesthesia (anesthesia/surgery). We subsequently investigated anesthesia/surgery caused behavioral changes and increased the expression of malondialdehyde (MAD), an oxidative stress marker, and the activities of superoxide dismutase (SOD), an antioxidant marker, in the mice at 6 h after anesthesia/surgery. However, GTP administration reversed these changes and alleviated anesthesia/surgery-induced decrease in the abundance of gut bacterial genera, Roseburia. Further, fecal microbiota transplant demonstrated that compared with mice in the control group, treatment of C57BL/6 mice with feces from GTP-treated mice had a slight effect on the behavioral changes of mice. These data suggest that daily consumption of GTP could protect against anesthesia/surgery-induced behavioral changes, which is closely associated with gut microbiota modification by GTP.}, }
@article {pmid38493312, year = {2024}, author = {Kalam, N and Balasubramaniam, VRMT}, title = {Crosstalk between COVID-19 and the gut-brain axis: a gut feeling.}, journal = {Postgraduate medical journal}, volume = {100}, number = {1186}, pages = {539-554}, doi = {10.1093/postmj/qgae030}, pmid = {38493312}, issn = {1469-0756}, support = {STG-000131//School Strategic Grants/ ; //Jeffrey Cheah School of Medicine &amp; Health Sciences/ ; //Monash University Malaysia/ ; }, mesh = {Humans ; *COVID-19/therapy/complications ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis ; *Brain-Gut Axis/physiology ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; *SARS-CoV-2 ; }, abstract = {The microbes in the gut are crucial for maintaining the body's immune system and overall gut health. However, it is not fully understood how an unstable gut environment can lead to more severe cases of SARS-CoV-2 infection. The gut microbiota also plays a role in the gut-brain axis and interacts with the central nervous system through metabolic and neuroendocrine pathways. The interaction between the microbiota and the host's body involves hormonal, immune, and neural pathways, and any disruption in the balance of gut bacteria can lead to dysbiosis, which contributes to pathogen growth. In this context, we discuss how dysbiosis could contribute to comorbidities that increase susceptibility to SARS-CoV-2. Probiotics and fecal microbiota transplantation have successfully treated infectious and non-infectious inflammatory-related diseases, the most common comorbidities. These treatments could be adjuvant therapies for COVID-19 infection by restoring gut homeostasis and balancing the gut microbiota.}, }
@article {pmid38492132, year = {2024}, author = {Maharshi, S and Sharma, BC}, title = {Prophylaxis of hepatic encephalopathy: current and future drug targets.}, journal = {Hepatology international}, volume = {18}, number = {4}, pages = {1096-1109}, pmid = {38492132}, issn = {1936-0541}, mesh = {*Hepatic Encephalopathy/prevention &amp; control/drug therapy ; Humans ; *Lactulose/therapeutic use ; *Rifaximin/therapeutic use ; Probiotics/therapeutic use ; Gastrointestinal Agents/therapeutic use ; Fecal Microbiota Transplantation/methods ; Liver Transplantation ; Secondary Prevention/methods ; Amino Acids, Branched-Chain/therapeutic use ; Primary Prevention/methods ; Dipeptides ; }, abstract = {Hepatic encephalopathy is described by a broad spectrum of neurological and psychiatric aberrations resulting due to advanced liver dysfunction. It is a neurological disorder due to hepatic insufficiency and/or portosystemic shunts. Its clinical presentation includes neuropsychiatric dysfunction ranging from subclinical changes to comatose state. It is a sign of poor prognosis in cirrhotics with a high 1-year mortality. Each episode of hepatic encephalopathy leads to high hospitalization rate, poor prognosis and raised burden of healthcare. Primary prophylaxis is prevention of initial occurrence and secondary prophylaxis is prevention of reappearance of hepatic encephalopathy in subjects who had prior history. Early detection and management of triggers is very important in the treatment of hepatic encephalopathy. The initial choice of treatment is still lactulose, as it is effective in minimal, overt, and recurrent hepatic encephalopathy. Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated. Branch chain amino acids are beneficial in subjects who are protein intolerant. L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy. Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy. Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients. Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy.}, }
@article {pmid38488837, year = {2024}, author = {Wang, F and Liu, X and Huang, F and Zhou, Y and Wang, X and Song, Z and Wang, S and Wang, X and Shi, D and Ruan, G and Ji, X and Zhang, E and Tan, Z and Ye, Y and Wang, C and Zhu, J and Wang, W}, title = {Gut microbiota-derived gamma-aminobutyric acid from metformin treatment reduces hepatic ischemia/reperfusion injury through inhibiting ferroptosis.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38488837}, issn = {2050-084X}, support = {2022R413C074//Zhejiang University Student Science and Technology Innovation Activity Plan/ ; LGF22H030011//Zhejiang Province Public Welfare Technology Application Research Project/ ; KJHX2212//Suzhou Inhale Pharma Co, Ltd/ ; KJHX2202//Zhejiang Xiaolun Intelligent Manufacturing Co, Ltd/ ; }, mesh = {Humans ; Mice ; Animals ; *Metformin/pharmacology ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; *Ferroptosis ; *Reperfusion Injury/drug therapy/metabolism ; Ischemia ; gamma-Aminobutyric Acid/pharmacology ; }, abstract = {Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was confirmed by the results of fecal microbiota transplantation treatment but showed the elimination of the beneficial effects when gut bacteria were depleted using antibiotics. Detailedly, through 16S rRNA and metagenomic sequencing, we identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria. This increase was further confirmed by the elevation of GABA synthesis key enzymes, glutamic acid decarboxylase and putrescine aminotransferase, in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated in GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, with GABA identified as a key metabolite.}, }
@article {pmid38488112, year = {2024}, author = {Frerichs, NM and de Meij, TGJ and Niemarkt, HJ}, title = {Microbiome and its impact on fetal and neonatal brain development: current opinion in pediatrics.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {27}, number = {3}, pages = {297-303}, pmid = {38488112}, issn = {1473-6519}, mesh = {Animals ; Female ; Humans ; Infant, Newborn ; Mice ; Brain/physiology ; *Infant, Premature ; *Microbiota ; *Mitoguazone/analogs &amp; derivatives ; Neurotransmitter Agents/metabolism ; }, abstract = {PURPOSE OF REVIEW: Emerging evidence suggests that the gut microbiota and its metabolites regulate neurodevelopment and cognitive functioning via a bi-directional communication system known as the microbiota-gut-brain axis (MGBA).<br><br>RECENT FINDINGS: The MGBA influences brain development and function via the hypothalamic-pituitary axis, the vagal nerve, immune signaling, bacterial production of neurotransmitters, and microbial metabolites like short-chain fatty acids, tryptophan derivatives, and bile acids. Animal studies show fetal neurodevelopment is mediated by maternal microbiota derivatives, immune activation, and diet. Furthermore, manipulation of the microbiota during critical windows of development, like antibiotic exposure and fecal microbiota transplantation, can affect cognitive functioning and behavior in mice. Evidence from human studies, particularly in preterm infants, also suggests that a disrupted gut microbiota colonization may negatively affect neurodevelopment. Early microbial signatures were linked to favorable and adverse neurodevelopmental outcomes.<br><br>SUMMARY: The link between the gut microbiota and the brain is evident. Future studies, including experimental studies, larger participant cohort studies with longitudinal analyses of microbes, their metabolites, and neurotransmitters, and randomized controlled trials are warranted to further elucidate the mechanisms of the MGBA. Identification of early, predictive microbial markers could pave the way for the development of novel early microbiota-based intervention strategies, such as targeted probiotics, and vaginal or fecal microbiota transplantation, aimed at improving infant neurodevelopment.}, }
@article {pmid38485738, year = {2024}, author = {Di, Y and Song, Y and Xu, K and Wang, Q and Zhang, L and Liu, Q and Zhang, M and Liu, X and Wang, Y}, title = {Chicoric Acid Alleviates Colitis via Targeting the Gut Microbiota Accompanied by Maintaining Intestinal Barrier Integrity and Inhibiting Inflammatory Responses.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {12}, pages = {6276-6288}, doi = {10.1021/acs.jafc.3c08363}, pmid = {38485738}, issn = {1520-5118}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Colitis ; Intestines ; Caffeic Acids ; *Colitis, Ulcerative ; Polyphenols ; Dextran Sulfate ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon ; *Succinates ; }, abstract = {Polyphenols have shown great potential to prevent ulcerative colitis. As a natural plant polyphenol, chicoric acid (CA) has antioxidant and anti-inflammatory properties. This study explored the intervention effects and potential mechanism of CA on dextran sodium sulfate (DSS)-induced colitis mice. The results showed that CA alleviated the symptoms of colitis and maintained the intestinal barrier integrity. CA significantly downregulated the mRNA expression levels of inflammatory factors including IL-6, IL-1β, TNF-α, IFN-γ, COX-2, and iNOS. In addition, CA modulated the gut microbiota by improving the microbial diversity, reducing the abundance of Gammaproteobacteriaand Clostridium_XI and increasing the abundance ofBarnesiellaandLachnospiraceae. Further fecal microbiota transplantation experiments showed that FM from CA donor mice significantly alleviated the symptoms of colitis, verifying the key role of gut microbiota. These results indicate that CA effectively relieves DSS-induced colitis via targeting gut microbiota along with preserving intestinal barrier function and suppressing inflammatory responses.}, }
@article {pmid38485702, year = {2024}, author = {Li, L and Huang, X and Chen, H}, title = {Unveiling the hidden players: exploring the role of gut mycobiome in cancer development and treatment dynamics.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2328868}, pmid = {38485702}, issn = {1949-0984}, mesh = {Humans ; *Mycobiome ; *Gastrointestinal Microbiome ; Fungi/genetics ; Carcinogenesis ; Cell Transformation, Neoplastic ; }, abstract = {The role of gut fungal species in tumor-related processes remains largely unexplored, with most studies still focusing on fungal infections. This review examines the accumulating evidence suggesting the involvement of commensal and pathogenic fungi in cancer biological process, including oncogenesis, progression, and treatment response. Mechanisms explored include fungal influence on host immunity, secretion of bioactive toxins/metabolites, interaction with bacterial commensals, and migration to other tissues in certain types of cancers. Attempts to utilize fungal molecular signatures for cancer diagnosis and fungal-derived products for treatment are discussed. A few studies highlight fungi's impact on the responsiveness and sensitivity to chemotherapy, radiotherapy, immunotherapy, and fecal microbiota transplant. Given the limited understanding and techniques in fungal research, the studies on gut fungi are still facing great challenges, despite having great potentials.}, }
@article {pmid38484559, year = {2024}, author = {Wang, S and Li, X and Zhang, B and Li, Y and Chen, K and Qi, H and Gao, M and Rong, J and Liu, L and Wan, Y and Dong, X and Yan, M and Ma, L and Li, P and Zhao, T}, title = {Tangshen formula targets the gut microbiota to treat non-alcoholic fatty liver disease in HFD mice: A 16S rRNA and non-targeted metabolomics analyses.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {173}, number = {}, pages = {116405}, doi = {10.1016/j.biopha.2024.116405}, pmid = {38484559}, issn = {1950-6007}, mesh = {Mice ; Animals ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; RNA, Ribosomal, 16S/genetics/metabolism ; *Gastrointestinal Microbiome ; Liver ; Diet, High-Fat/adverse effects ; Anti-Bacterial Agents/pharmacology ; Mice, Inbred C57BL ; *Drugs, Chinese Herbal ; }, abstract = {BACKGROUND: Tangshen formula (TSF) has an ameliorative effect on hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD), but the role played by the gut microbiota in this process is unknown.<br><br>METHOD: We conducted three batches of experiments to explore the role played by the gut microbiota: TSF administration, antibiotic treatment, and fecal microbial transplantation. NAFLD mice were induced with a high-fat diet to investigate the ameliorative effects of TSF on NAFLD features and intestinal barrier function. 16S rRNA sequencing and serum untargeted metabolomics were performed to further investigate the modulatory effects of TSF on the gut microbiota and metabolic dysregulation in the body.<br><br>RESULTS: TSF ameliorated insulin resistance, hypercholesterolemia, lipid metabolism disorders, inflammation, and impairment of intestinal barrier function. 16S rRNA sequencing analysis revealed that TSF regulated the composition of the gut microbiota and increased the abundance of beneficial bacteria. Antibiotic treatment and fecal microbiota transplantation confirmed the importance of the gut microbiota in the treatment of NAFLD with TSF. Subsequently, untargeted metabolomics identified 172 differential metabolites due to the treatment of TSF. Functional predictions suggest that metabolisms of choline, glycerophospholipid, linoleic acid, alpha-linolenic acid, and arachidonic acid are the key metabolic pathways by which TSF ameliorates NAFLD and this may be influenced by the gut microbiota.<br><br>CONCLUSION: TSF treats the NAFLD phenotype by remodeling the gut microbiota and improving metabolic profile, suggesting that TSF is a functional gut microbial and metabolic modulator for the treatment of NAFLD.}, }
@article {pmid38484370, year = {2024}, author = {Yao, Y and Wang, X and Li, D and Chen, S and Li, C and Guan, H and Wang, D and Nie, X}, title = {Cyclocarya paliurus leaves alleviate high-sucrose diet-induced obesity by improving intestinal metabolic disorders.}, journal = {Aging}, volume = {16}, number = {6}, pages = {5452-5470}, pmid = {38484370}, issn = {1945-4589}, mesh = {Mice ; Humans ; Animals ; Sucrose ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Obesity/metabolism ; *Intestinal Diseases ; *Metabolic Diseases ; *Animals, Outbred Strains ; }, abstract = {High-sucrose diets are common in daily life but harmful to human health. Cyclocarya paliurus leaves (CPL) are a kind of tea used to alleviate metabolic diseases and are widely used in China. However, the effects of CPL on high-sucrose-induced obesity are unknown. This study aimed to describe the changes in gut metabolism induced by a high-sucrose diet and to reveal the potential mechanisms through which CPL alleviate high-sucrose diet-induced obesity. A high-sucrose-induced obesity model was generated in C57BL/6J and KM mice. The effects of CPL on obese mice were evaluated, and changes in the gut microbiota and intestinal metabolites induced by CPL treatment were observed. Furthermore, the fecal microbiota transplantation (FMT) method was used to prove that the effects of CPL on high-sucrose induced obesity depend on the changes of gut microbiota. The results of the C57BL/6J mouse experiment revealed that high-sucrose intake induced fat deposition and altered the gut microbiota. CPL treatment decreased fat deposition and alleviated disorders of the gut microbiota. Furthermore, CPL treatment increased the utilization of amnio acids, long fatty acids and saccharides and produced more bile acids, indole derivatives and less trimethylamine (TMA). A confirmatory experiment in KM mice also revealed that CPL can alleviate obesity, ameliorate intestinal metabolic disorders, and upregulate the expression of tight junction proteins in the intestinal mucosa. These results demonstrated that CPL could prevent high sucrose-induced obesity and generate more beneficial intestinal microbial metabolites but less harmful intestinal microbial metabolites.}, }
@article {pmid38479921, year = {2024}, author = {Peddinti, V and Avaghade, MM and Suthar, SU and Rout, B and Gomte, SS and Agnihotri, TG and Jain, A}, title = {Gut instincts: Unveiling the connection between gut microbiota and Alzheimer's disease.}, journal = {Clinical nutrition ESPEN}, volume = {60}, number = {}, pages = {266-280}, doi = {10.1016/j.clnesp.2024.02.019}, pmid = {38479921}, issn = {2405-4577}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Alzheimer Disease ; Dysbiosis ; Instinct ; Neuroinflammatory Diseases ; }, abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder marked by neuroinflammation and gradual cognitive decline. Recent research has revealed that the gut microbiota (GM) plays an important role in the pathogenesis of AD through the microbiota-gut-brain axis. However, the mechanism by which GM and microbial metabolites alter brain function is not clearly understood. GM dysbiosis increases the permeability of the intestine, alters the blood-brain barrier permeability, and elevates proinflammatory mediators causing neurodegeneration. This review article introduced us to the composition and functions of GM along with its repercussions of dysbiosis in relation to AD. We also discussed the importance of the gut-brain axis and its role in communication. Later we focused on the mechanism behind gut dysbiosis and the progression of AD including neuroinflammation, oxidative stress, and changes in neurotransmitter levels. Furthermore, we highlighted recent developments in AD management, such as microbiota-based therapy, dietary interventions like prebiotics, probiotics, and fecal microbiota transplantation. Finally, we concluded with challenges and future directions in AD research based on GM.}, }
@article {pmid38479258, year = {2024}, author = {Wang, H and Zhu, W and Hong, Y and Wei, W and Zheng, N and He, X and Bao, Y and Gao, X and Huang, W and Sheng, L and Li, M and Li, H}, title = {Astragalus polysaccharides attenuate chemotherapy-induced immune injury by modulating gut microbiota and polyunsaturated fatty acid metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {128}, number = {}, pages = {155492}, doi = {10.1016/j.phymed.2024.155492}, pmid = {38479258}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/pharmacology ; *Fluorouracil ; Mice ; *Astragalus Plant/chemistry ; *Fatty Acids, Unsaturated/pharmacology ; Intestinal Mucosa/drug effects ; Male ; Mice, Inbred C57BL ; Spleen/drug effects ; Fecal Microbiota Transplantation ; Colon/drug effects ; }, abstract = {BACKGROUND: The damage of chemotherapy drugs to immune function and intestinal mucosa is a common side effect during chemotherapy. Astragalus polysaccharides (APS) exhibit immunomodulatory properties and are recognized for preserving the integrity of the human intestinal barrier. Nevertheless, their application and mechanisms of action in chemotherapy-induced immune damage and intestinal barrier disruption remain insufficiently explored.<br><br>PURPOSE: This study delved into investigating how APS mitigates chemotherapy-induced immune dysfunction and intestinal mucosal injury, while also providing deeper insights into the underlying mechanisms.<br><br>METHODS: In a chemotherapy mice model induced by 5-fluorouracil (5-Fu), the assessment of APS's efficacy encompassed evaluations of immune organ weight, body weight, colon length, and histopathology. The regulation of different immune cells in spleen was detected by flow cytometry. 16S rRNA gene sequencings, ex vivo microbiome assay, fecal microbiota transplantation (FMT), and targeted metabolomics analysis were applied to explore the mechanisms of APS effected on chemotherapy-induced mice.<br><br>RESULTS: APS ameliorated chemotherapy-induced damage to immune organs and regulated immune cell differentiation disorders, including CD4[+]T, CD8[+]T, CD19[+]B, F4/80[+]CD11B[+] macrophages. APS also alleviated colon shortening and upregulated the expression of intestinal barrier proteins. Furthermore, APS significantly restored structure of gut microbiota following chemotherapy intervention. Ex vivo microbiome assays further demonstrated the capacity of APS to improve 5-Fu-induced microbiota growth inhibition and compositional change. FMT demonstrated that the regulation of gut microbiota by APS could promote the recovery of immune functions and alleviate shortening of the colon length. Remarkably, APS significantly ameliorated the imbalance of linoleic acid (LA) and &#x3b1;-linolenic acid in polyunsaturated fatty acid (PUFA) metabolism. Further in vitro experiments showed that LA could promote splenic lymphocyte proliferation. In addition, both LA and DGLA down-regulated the secretion of NO and partially up-regulated the percentage of F4/80[+]CD11B[+]CD206[+] cells.<br><br>CONCLUSION: APS can effectively ameliorate chemotherapy-induced immune damage and intestinal mucosal disruption by regulating the composition of the gut microbiota and further restoring PUFA metabolism. These findings indicate that APS can serve as an adjuvant to improve the side effects such as intestinal and immune damage caused by chemotherapy.}, }
@article {pmid38478462, year = {2024}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Kazadi, D and Halaweish, H and Khan, MH and Hoeschen, A and Cao, Q and Luo, X and Kabage, AJ and Lopez, S and Holtan, SG and Weisdorf, DJ and Liu, C and Ishii, S and Khoruts, A and Staley, C}, title = {Long- and short-term effects of fecal microbiota transplantation on antibiotic resistance genes: results from a randomized placebo-controlled trial.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2327442}, pmid = {38478462}, issn = {1949-0984}, support = {KL2 TR002492/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Anti-Bacterial Agents/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/genetics ; Treatment Outcome ; Drug Resistance, Microbial ; Feces ; }, abstract = {In small series, third-party fecal microbiota transplantation (FMT) has been successful in decolonizing the gut from clinically relevant antibiotic resistance genes (ARGs). Less is known about the short- and long-term effects of FMT on larger panels of ARGs. We analyzed 226 pre- and post-treatment stool samples from a randomized placebo-controlled trial of FMT in 100 patients undergoing allogeneic hematopoietic cell transplantation or receiving anti-leukemia induction chemotherapy for 47 ARGs. These patients have heavy antibiotic exposure and a high incidence of colonization with multidrug-resistant organisms. Samples from each patient spanned a period of up to 9 months, allowing us to describe both short- and long-term effects of FMT on ARGs, while the randomized design allowed us to distinguish between spontaneous changes vs. FMT effect. We find an overall bimodal pattern. In the first phase (days to weeks after FMT), low-level transfer of ARGs largely associated with commensal healthy donor microbiota occurs. This phase is followed by long-term resistance to new ARGs as stable communities with colonization resistance are formed after FMT. The clinical implications of these findings are likely context-dependent and require further research. In the setting of cancer and intensive therapy, long-term ARG decolonization could translate into fewer downstream infections.}, }
@article {pmid38475913, year = {2024}, author = {Sangiorgio, M and Middleton, C and Wilson, M and Osler, W and Patwardan, A}, title = {A case of fulminant severe Clostridioides difficile colitis managed with faecal microbial transplantation.}, journal = {Internal medicine journal}, volume = {54}, number = {3}, pages = {518-520}, doi = {10.1111/imj.16354}, pmid = {38475913}, issn = {1445-5994}, mesh = {Humans ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; *Clostridium Infections ; *Colitis ; }, }
@article {pmid38473999, year = {2024}, author = {Jang, JH and Jang, SY and Ahn, S and Oh, JY and Yeom, M and Ko, SJ and Park, JW and Kwon, SK and Kim, K and Lee, IS and Hahm, DH and Park, HJ}, title = {Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38473999}, issn = {1422-0067}, support = {NRF-2021R1A2C2006818//National Research Foundation of Korea/ ; 2022M3A9B6017813//National Research Foundation of Korea/ ; }, mesh = {Humans ; Animals ; Mice ; *Irritable Bowel Syndrome ; *Dermatitis, Atopic ; Dysbiosis ; *Gastrointestinal Microbiome/physiology ; Feces ; Fecal Microbiota Transplantation ; Inflammation ; }, abstract = {Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.}, }
@article {pmid38473913, year = {2024}, author = {Teschke, R}, title = {Hemochromatosis: Ferroptosis, ROS, Gut Microbiome, and Clinical Challenges with Alcohol as Confounding Variable.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38473913}, issn = {1422-0067}, mesh = {Humans ; *Hemochromatosis/genetics ; Hepcidins/metabolism ; Reactive Oxygen Species/metabolism ; *Alcoholism/complications ; *Ferroptosis ; Artificial Intelligence ; *Gastrointestinal Microbiome ; Confounding Factors, Epidemiologic ; Histocompatibility Antigens Class I/genetics ; Hemochromatosis Protein/metabolism ; Membrane Proteins/metabolism ; Iron/metabolism ; *Iron Overload/genetics ; Ferritins ; Ethanol ; *Liver Neoplasms/complications ; }, abstract = {Hemochromatosis represents clinically one of the most important genetic storage diseases of the liver caused by iron overload, which is to be differentiated from hepatic iron overload due to excessive iron release from erythrocytes in patients with genetic hemolytic disorders. This disorder is under recent mechanistic discussion regarding ferroptosis, reactive oxygen species (ROS), the gut microbiome, and alcohol abuse as a risk factor, which are all topics of this review article. Triggered by released intracellular free iron from ferritin via the autophagic process of ferritinophagy, ferroptosis is involved in hemochromatosis as a specific form of iron-dependent regulated cell death. This develops in the course of mitochondrial injury associated with additional iron accumulation, followed by excessive production of ROS and lipid peroxidation. A low fecal iron content during therapeutic iron depletion reduces colonic inflammation and oxidative stress. In clinical terms, iron is an essential trace element required for human health. Humans cannot synthesize iron and must take it up from iron-containing foods and beverages. Under physiological conditions, healthy individuals allow for iron homeostasis by restricting the extent of intestinal iron depending on realistic demand, avoiding uptake of iron in excess. For this condition, the human body has no chance to adequately compensate through removal. In patients with hemochromatosis, the molecular finetuning of intestinal iron uptake is set off due to mutations in the high-FE[2+] (HFE) genes that lead to a lack of hepcidin or resistance on the part of ferroportin to hepcidin binding. This is the major mechanism for the increased iron stores in the body. Hepcidin is a liver-derived peptide, which impairs the release of iron from enterocytes and macrophages by interacting with ferroportin. As a result, iron accumulates in various organs including the liver, which is severely injured and causes the clinically important hemochromatosis. This diagnosis is difficult to establish due to uncharacteristic features. Among these are asthenia, joint pain, arthritis, chondrocalcinosis, diabetes mellitus, hypopituitarism, hypogonadotropic hypogonadism, and cardiopathy. Diagnosis is initially suspected by increased serum levels of ferritin, a non-specific parameter also elevated in inflammatory diseases that must be excluded to be on the safer diagnostic side. Diagnosis is facilitated if ferritin is combined with elevated fasting transferrin saturation, genetic testing, and family screening. Various diagnostic attempts were published as algorithms. However, none of these were based on evidence or quantitative results derived from scored key features as opposed to other known complex diseases. Among these are autoimmune hepatitis (AIH) or drug-induced liver injury (DILI). For both diseases, the scored diagnostic algorithms are used in line with artificial intelligence (AI) principles to ascertain the diagnosis. The first-line therapy of hemochromatosis involves regular and life-long phlebotomy to remove iron from the blood, which improves the prognosis and may prevent the development of end-stage liver disease such as cirrhosis and hepatocellular carcinoma. Liver transplantation is rarely performed, confined to acute liver failure. In conclusion, ferroptosis, ROS, the gut microbiome, and concomitant alcohol abuse play a major contributing role in the development and clinical course of genetic hemochromatosis, which requires early diagnosis and therapy initiation through phlebotomy as a first-line treatment.}, }
@article {pmid38473143, year = {2024}, author = {Boucher, L and Leduc, L and Leclère, M and Costa, MC}, title = {Current Understanding of Equine Gut Dysbiosis and Microbiota Manipulation Techniques: Comparison with Current Knowledge in Other Species.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {5}, pages = {}, pmid = {38473143}, issn = {2076-2615}, abstract = {Understanding the importance of intestinal microbiota in horses and the factors influencing its composition have been the focus of many studies over the past few years. Factors such as age, diet, antibiotic administration, and geographic location can affect the gut microbiota. The intra- and inter-individual variability of fecal microbiota in horses complicates its interpretation and has hindered the establishment of a clear definition for dysbiosis. Although a definitive causal relationship between gut dysbiosis in horses and diseases has not been clearly identified, recent research suggests that dysbiosis may play a role in the pathogenesis of various conditions, such as colitis and asthma. Prebiotics, probiotics, and fecal microbiota transplantation to modulate the horse's gastrointestinal tract may eventually be considered a valuable tool for preventing or treating diseases, such as antibiotic-induced colitis. This article aims to summarize the current knowledge on the importance of intestinal microbiota in horses and factors influencing its composition, and also to review the published literature on methods for detecting dysbiosis while discussing the efficacy of gut microbiota manipulation in horses.}, }
@article {pmid38472547, year = {2024}, author = {Homma, Y and Mimura, T and Koinuma, K and Horie, H and Sata, N}, title = {Incidence of low anterior resection syndrome and its association with the quality of life in patients with lower rectal tumors.}, journal = {Surgery today}, volume = {54}, number = {8}, pages = {857-865}, pmid = {38472547}, issn = {1436-2813}, mesh = {Humans ; *Quality of Life ; *Rectal Neoplasms/surgery ; Incidence ; Syndrome ; Risk Factors ; Male ; Female ; *Postoperative Complications/epidemiology/etiology ; Aged ; Middle Aged ; *Fecal Incontinence/etiology/epidemiology ; Digestive System Surgical Procedures ; Neoadjuvant Therapy ; Surveys and Questionnaires ; Organ Sparing Treatments/methods ; Anal Canal/surgery ; Defecation ; Adult ; Aged, 80 and over ; Time Factors ; Low Anterior Resection Syndrome ; }, abstract = {PURPOSE: Low anterior resection syndrome (LARS) causes devastating symptoms and impairs the quality of life (QOL). This study investigated the incidence and risk factors of LARS and their association with the QOL in patients with lower rectal tumors.<br><br>METHODS: Patients who underwent anus-preserving surgery for lower rectal tumors between 2014 and 2019 and who had anal defecation between 2020 and 2021 were surveyed. The LARS score measured severity, and the QOL was evaluated using the Japanese version of the Fecal Incontinence Quality-of-Life Scale (JFIQL). The primary endpoint was the incidence of Major LARS, and the secondary endpoints were risk factors and association with the JFIQL.<br><br>RESULTS: Of 107 eligible patients, 82 (76.6%) completed the LARS survey. The incidence of Major LARS was 48%. Independent risk factors included neoadjuvant chemoradiotherapy (CRT) and a short interval (<&#x2009;24&#xa0;months after surgery; odds ratio, 4.6; 95% confidence interval: 1.1-19, both). The LARS score was moderately correlated with the JFIQL generic score (correlation coefficient: -&#x2009;0.54). The JFIQL scores were significantly worse in the Minor and Major LARS groups than in the No LARS group.<br><br>CONCLUSIONS: Major LARS was found in 48% of lower rectal tumors, and independent risk factors include neoadjuvant CRT and a short interval. The QOL was significantly impaired in patients with both Minor and Major LARS.}, }
@article {pmid38472186, year = {2024}, author = {Zhu, J and Bao, Z and Hu, Z and Wu, S and Tian, C and Zhou, Y and Ding, Z and Tan, X}, title = {Myricetin alleviates diabetic cardiomyopathy by regulating gut microbiota and their metabolites.}, journal = {Nutrition &amp; diabetes}, volume = {14}, number = {1}, pages = {10}, pmid = {38472186}, issn = {2044-4052}, support = {No. 2023A1515011969, 2019A1515011817//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; No. 81900347//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; Mice ; *Diabetic Cardiomyopathies ; *Gastrointestinal Microbiome ; Occludin/pharmacology ; Hypertrophy ; Mice, Inbred C57BL ; Diet, High-Fat ; *Diabetes Mellitus ; *Flavonoids ; }, abstract = {BACKGROUND: The gut microbiota is involved in the pathogenesis of diabetic cardiomyopathy (DCM). Myricetin protects cardiac function in DCM. However, the low bioavailability of myricetin fails to explain its pharmacological mechanisms thoroughly. Research has shown that myricetin has a positive effect on the gut microbiota. We hypothesize that myricetin improves the development of DCM via regulating gut microbiota.<br><br>METHODS: DCM mice were induced with streptozotocin and fed a high-fat diet, and then treated with myricetin by gavage and high-fat diet for 16 weeks. Indexes related to gut microbiota composition, cardiac structure, cardiac function, intestinal barrier function, and inflammation were detected. Moreover, the gut contents were transplanted to DCM mice, and the effect of fecal microbiota transplantation (FMT) on DCM mice was assessed.<br><br>RESULTS: Myricetin could improve cardiac function in DCM mice by decreasing cardiomyocyte hypertrophy and interstitial fibrosis. The composition of gut microbiota, especially for short-chain fatty acid-producing bacteria involving Roseburia, Faecalibaculum, and Bifidobacterium, was more abundant by myricetin treatment in DCM mice. Myricetin increased occludin expression and the number of goblet cells in DCM mice. Compared with DCM mice unfed with gut content, the cardiac function, number of goblet cells, and expression of occludin in DCM mice fed by gut contents were elevated, while cardiomyocyte hypertrophy and TLR4/MyD88 pathway-related proteins were decreased.<br><br>CONCLUSIONS: Myricetin can prevent DCM development by increasing the abundance of beneficial gut microbiota and restoring the gut barrier function.}, }
@article {pmid38471063, year = {2024}, author = {DeFilipp, Z and Damania, AV and Kim, HT and Chang, CC and El-Jawahri, A and McAfee, SL and Bottoms, AS and Toncheva, V and Smith, MM and Dolaher, M and Perry, L and White, M and Diana, B and Connolly, S and Dey, BR and Frigault, MJ and Newcomb, RA and O'Donnell, PV and Spitzer, TR and Mansour, MK and Weber, D and Ajami, NJ and Hohmann, E and Jenq, RR and Chen, YB}, title = {Third-party fecal microbiota transplantation for high-risk treatment-naïve acute GVHD of the lower GI tract.}, journal = {Blood advances}, volume = {8}, number = {9}, pages = {2074-2084}, pmid = {38471063}, issn = {2473-9537}, support = {R01 HL124112/HL/NHLBI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Graft vs Host Disease/therapy/etiology ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Middle Aged ; Adult ; Gastrointestinal Microbiome ; Aged ; Pilot Projects ; Acute Disease ; Treatment Outcome ; }, abstract = {Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% of participants able to swallow ≥40 of the 75 scheduled capsules. Ten participants (9 treatment-naïve; 1 steroid-refractory) were enrolled and treated. The study met the primary end point, with 9 of 10 participants completing all eligible doses. Organ-specific LGI complete response rate at day 28 was 70%. Initial clinical response was observed within 1 week for all responders, and clinical responses were durable without recurrent LGI GVHD in complete responders. Exploratory analyses suggest that alpha diversity increased after FMT. Although recipient microbiome composition never achieved a high degree of donor similarity, expansion of donor-derived species and increases in tryptophan metabolites and short-chain fatty acids were observed within the first 7 days after FMT. Investigation into the use of microbiome-targeted interventions earlier in the treatment paradigm for acute LGI GVHD is warranted. This trial was registered at www.ClinicalTrials.gov as #NCT04139577.}, }
@article {pmid38471012, year = {2024}, author = {Jiang, Y and Yang, J and Xia, L and Wei, T and Cui, X and Wang, D and Jin, Z and Lin, X and Li, F and Yang, K and Lang, S and Liu, Y and Hang, J and Zhang, Z and Hong, T and Wei, R}, title = {Gut Microbiota-Tryptophan Metabolism-GLP-1 Axis Participates in β-Cell Regeneration Induced by Dapagliflozin.}, journal = {Diabetes}, volume = {73}, number = {6}, pages = {926-940}, pmid = {38471012}, issn = {1939-327X}, support = {//Talent Project of Clinical Key Project of Peking University Third Hospital/ ; 82070319//National Natural Science Foundation of China/ ; //the National Clinical Key Specialty Construction Program, P. R. China (2023)/ ; PKU2023LCXQ025//Clinical Medicine Plus X-Young Scholars Project of Peking University/ ; 7222216//Beijing Municipal Natural Science Foundation/ ; XB202011//Tianjin Municipal Human Resources and Social Security Bureau/ ; }, mesh = {Animals ; *Benzhydryl Compounds/pharmacology ; *Insulin-Secreting Cells/metabolism/drug effects ; *Glucagon-Like Peptide 1/metabolism ; *Gastrointestinal Microbiome/drug effects/physiology ; *Tryptophan/metabolism ; Mice ; *Glucosides/pharmacology/therapeutic use ; *Regeneration/drug effects ; Humans ; Male ; Insulin/metabolism ; Blood Glucose/metabolism/drug effects ; Diabetes Mellitus, Type 2/metabolism/drug therapy/microbiology ; Mice, Inbred C57BL ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology ; Diabetes Mellitus, Experimental/metabolism ; Glucagon-Like Peptide-1 Receptor/metabolism ; }, abstract = {Sodium-glucose cotransporter 2 inhibitors, efficacious antidiabetic agents that have cardiovascular and renal benefits, can promote pancreatic β-cell regeneration in type 2 diabetic mice. However, the underlying mechanism remains unclear. In this study, we aimed to use multiomics to identify the mediators involved in β-cell regeneration induced by dapagliflozin. We showed that dapagliflozin lowered blood glucose level, upregulated plasma insulin level, and increased islet area in db/db mice. Dapagliflozin reshaped gut microbiota and modulated microbiotic and plasmatic metabolites related to tryptophan metabolism, especially l-tryptophan, in the diabetic mice. Notably, l-tryptophan upregulated the mRNA level of glucagon-like peptide 1 (GLP-1) production-related gene (Gcg and Pcsk1) expression and promoted GLP-1 secretion in cultured mouse intestinal L cells, and it increased the supernatant insulin level in primary human islets, which was eliminated by GPR142 antagonist. Transplant of fecal microbiota from dapagliflozin-treated mice, supplementation of l-tryptophan, or treatment with dapagliflozin upregulated l-tryptophan, GLP-1, and insulin or C-peptide levels and promoted β-cell regeneration in db/db mice. Addition of exendin 9-39, a GLP-1 receptor (GLP-1R) antagonist, or pancreatic Glp1r knockout diminished these beneficial effects. In summary, treatment with dapagliflozin in type 2 diabetic mice promotes β-cell regeneration by upregulating GLP-1 production, which is mediated via gut microbiota and tryptophan metabolism.}, }
@article {pmid38470843, year = {2024}, author = {Chen, H and Ye, L and Wang, Y and Chen, J and Wang, J and Li, X and Lei, H and Liu, Y}, title = {Aflatoxin B1 exposure causes splenic pyroptosis by disturbing the gut microbiota-immune axis.}, journal = {Food &amp; function}, volume = {15}, number = {7}, pages = {3615-3628}, doi = {10.1039/d3fo04717b}, pmid = {38470843}, issn = {2042-650X}, mesh = {Animals ; Mice ; *Pyroptosis ; Aflatoxin B1/toxicity ; Spleen ; *Gastrointestinal Microbiome ; Feces ; }, abstract = {Aflatoxin B1 (AFB1) causes serious immunotoxicity and has attracted considerable attention owing to its high sensitivity and common chemical-viral interactions in living organisms. However, the sensitivity of different species to AFB1 widely varies, which cannot be explained by the different metabolism in species. The gut microbiota plays a crucial role in the immune system, but the interaction of the microbiota with AFB1-induced immunotoxicity still needs to be determined. Our results indicated that AFB1 exposure disrupted the structure of the gut microbiota and damaged the gut barrier, which caused translocation of microbiota metabolites, lipopolysaccharides, to the spleen. Subsequently, pyroptosis of the spleen was activated. Interestingly, AFB1 exposure had little effect on the splenic pyroptosis of pseudo-germfree mice (antibiotic mixtures eliminated their gut microbiota, ABX). Then, fecal microbiota transplant (FMT) and sterile fecal filtrate (SFF) were employed to validate the function of the gut microbiota and its metabolites in AFB1-induced splenic pyroptosis. The AFB1-disrupted microbiota and its metabolites significantly promoted splenic pyroptosis, which was worse than that in control mice. Overall, AFB1-induced splenic pyroptosis is associated with the gut microbiota and its metabolites, which was further demonstrated by FMT and SFF. The mechanism of AFB1-induced splenic pyroptosis was explored for the first time, which paves a new way for preventing and treating the immunotoxicity from mycotoxins by regulating the gut microbiota.}, }
@article {pmid38470061, year = {2024}, author = {Hunt, A and Drwiega, E and Wang, Y and Danziger, L}, title = {A review of fecal microbiota, live-jslm for the prevention of recurrent Clostridioides difficile infection.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {81}, number = {15}, pages = {e402-e411}, doi = {10.1093/ajhp/zxae066}, pmid = {38470061}, issn = {1535-2900}, mesh = {Humans ; *Clostridium Infections/prevention &amp; control/microbiology ; *Fecal Microbiota Transplantation/methods ; *Clostridioides difficile/isolation &amp; purification/drug effects ; Feces/microbiology ; Anti-Bacterial Agents/administration &amp; dosage/therapeutic use/adverse effects ; Gastrointestinal Microbiome/drug effects ; Recurrence ; Randomized Controlled Trials as Topic ; Secondary Prevention/methods ; }, abstract = {PURPOSE: To review the composition, preparation, proposed mechanism of action, safety, efficacy, and current place in therapy of Rebyota (fecal microbiota, live-jslm).<br><br>SUMMARY: As the first agent in a new class of drugs, live biotherapeutic products (LBPs), fecal microbiota, live-jslm offers another therapeutic approach for the prevention of recurrent Clostridioides difficile infection (rCDI). LBPs are given following antibiotic therapy for C. difficile to reintroduce certain bacteria present in the normal microbiome, as a means to reconstitute the microbiome of infected individuals. This review provides a summary of phase 2 and 3 clinical trials, product information, discussion of data limitations, and recommendations for place in therapy. High efficacy rates compared to placebo with sustained response up to 24 months after administration have been reported. The majority of adverse events identified were mild to moderate without significant safety signals.<br><br>CONCLUSION: Fecal microbiota, live-jslm has consistently been shown in randomized trials to be safe and effective in reducing rCDI. Its approval marks the culmination of decades of work to identify, characterize, and refine the intestinal microbiome to create pharmaceutical products.}, }
@article {pmid38467249, year = {2024}, author = {Mullish, BH and Bak, A and Merrick, B and Quraishi, MN and Goldenberg, SD and Williams, HRT}, title = {Overview of the second edition of the joint British Society of Gastroenterology and Healthcare Infection Society faecal microbiota transplant guidelines, 2024.}, journal = {The Journal of hospital infection}, volume = {148}, number = {}, pages = {178-188}, doi = {10.1016/j.jhin.2024.02.021}, pmid = {38467249}, issn = {1532-2939}, mesh = {Humans ; *Fecal Microbiota Transplantation ; United Kingdom ; Practice Guidelines as Topic ; Clostridium Infections/prevention &amp; control/microbiology ; Gastroenterology/standards ; }, }
@article {pmid38466881, year = {2024}, author = {Yang, H and Liu, Q and Liu, H and Kang, X and Tian, H and Kang, Y and Li, L and Yang, X and Ren, P and Kuang, X and Wang, X and Guo, L and Tong, M and Ma, J and Fan, W}, title = {Berberine alleviates concanavalin A-induced autoimmune hepatitis in mice by modulating the gut microbiota.}, journal = {Hepatology communications}, volume = {8}, number = {4}, pages = {}, pmid = {38466881}, issn = {2471-254X}, mesh = {Mice ; Animals ; *Hepatitis, Autoimmune/drug therapy/etiology ; *Berberine/pharmacology/therapeutic use ; Concanavalin A/pharmacology ; Lipopolysaccharides/pharmacology ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; *Hepatitis A ; }, abstract = {BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology accompanied by intestinal dysbiosis and a damaged intestinal barrier. Berberine (BBR) is a traditional antibacterial medicine that has a variety of pharmacological properties. It has been reported that BBR alleviates AIH, but relevant mechanisms remain to be fully explored.<br><br>METHODS: BBR was orally administered at doses of 100&#xa0;mg&#x22c5;kg-1&#x22c5;d-1 for 7 days to mice before concanavalin A-induced AIH model establishment. Histopathological, immunohistochemical, immunofluorescence, western blotting, ELISA, 16S rRNA analysis, flow cytometry, real-time quantitative PCR, and fecal microbiota transplantation studies were performed to ascertain BBR effects and mechanisms in AIH mice.<br><br>RESULTS: We found that liver necrosis and apoptosis were decreased upon BBR administration; the levels of serum transaminase, serum lipopolysaccharide, liver proinflammatory factors TNF-&#x3b1;, interferon-&#x3b3;, IL-1&#x3b2;, and IL-17A, and the proportion of Th17 cells in spleen cells were all reduced, while the anti-inflammatory factor IL-10 and regulatory T cell proportions were increased. Moreover, BBR treatment increased beneficial and reduced harmful bacteria in the gut. BBR also strengthened ileal barrier function by increasing the expression of the tight junction proteins zonula occludens-1 and occludin, thereby blocking lipopolysaccharide translocation, preventing lipopolysaccharide/toll-like receptor 4 (TLR4)/ NF-&#x3ba;B pathway activation, and inhibiting inflammatory factor production in the liver. Fecal microbiota transplantation from BBR to model mice also showed that BBR potentially alleviated AIH by altering the gut microbiota.<br><br>CONCLUSIONS: BBR alleviated concanavalin A-induced AIH by modulating the gut microbiota and related immune regulation. These results shed more light on potential BBR therapeutic strategies for AIH.}, }
@article {pmid38464968, year = {2024}, author = {Lazar, L and Eshel, A and Moadi, L and Yackobovitch-Gavan, M and Bar-Maisels, M and Shtaif, B and Nevo, M and Phillip, M and Turjeman, S and Koren, O and Gat-Yablonski, G}, title = {Children with idiopathic short stature have significantly different gut microbiota than their normal height siblings: a case-control study.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1343337}, pmid = {38464968}, issn = {1664-2392}, mesh = {Child ; Humans ; Mice ; Animals ; *Siblings ; Case-Control Studies ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Growth Disorders/etiology ; }, abstract = {OBJECTIVES: To investigate the role of gut microbiota (GM) in pathogenesis of idiopathic short stature (ISS) by comparing GM of ISS children to their normal-height siblings.<br><br>METHODS: This case-control study, conducted at the Schneider Children's Medical Center's Institute for Endocrinology and Diabetes between 4/2018-11/2020, involved 30 pairs of healthy pre-pubertal siblings aged 3-10 years, each comprising one sibling with ISS and one with normal height. Outcome measures from fecal analysis of both siblings included GM composition analyzed by 16S rRNA sequencing, fecal metabolomics, and monitoring the growth of germ-free (GF) mice after fecal transplantation.<br><br>RESULTS: Fecal analysis of ISS children identified higher predicted levels of genes encoding enzymes for pyrimidine, purine, flavin, coenzyme B, and thiamine biosynthesis, lower levels of several amino acids, and a significantly higher prevalence of the phylum Euryarchaeota compared to their normal-height siblings (p<0.001). ISS children with higher levels of Methanobrevibacter, the dominant species in the archaeal gut community, were significantly shorter in stature than those with lower levels (p=0.022). Mice receiving fecal transplants from ISS children did not experience stunted growth, probably due to the eradication of Methanobrevibacter caused by exposure to oxygen during fecal collection.<br><br>DISCUSSION: Our findings suggest that different characteristics in the GM may explain variations in linear growth. The varying levels of Methanobrevibacter demonstrated within the ISS group reflect the multifactorial nature of ISS and the potential ability of the GM to partially explain growth variations. The targeting of specific microbiota could provide personalized therapies to improve growth in children with ISS.}, }
@article {pmid38464791, year = {2024}, author = {Bai, X and Fu, R and Liu, Y and Deng, J and Fei, Q and Duan, Z and Zhu, C and Fan, D}, title = {Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis.}, journal = {Journal of pharmaceutical analysis}, volume = {14}, number = {2}, pages = {259-275}, pmid = {38464791}, issn = {2214-0883}, abstract = {The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer (CRC). However, the effect of ginsenoside Rk3 (Rk3) on CRC and gut microbiota remains unclear. Therefore, the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation. Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors, repairs intestinal barrier damage, and regulates the gut microbiota imbalance caused by CRC, including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis, and clearance of pathogenic Desulfovibrio. Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids, particularly by upregulating glutamine, which has the potential to regulate the immune response. Furthermore, we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells (ILC3s) and T helper 17 (Th17) signaling pathways, which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway. These results indicate that Rk3 modulates gut microbiota, regulates ILC3s immune response, and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors. More importantly, the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota. In summary, these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.}, }
@article {pmid38464781, year = {2024}, author = {Hui, H and Wang, Z and Zhao, X and Xu, L and Yin, L and Wang, F and Qu, L and Peng, J}, title = {Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata (Desv.) Spring against inflammatory bowel disease.}, journal = {Journal of pharmaceutical analysis}, volume = {14}, number = {2}, pages = {177-195}, pmid = {38464781}, issn = {2214-0883}, abstract = {Inflammatory bowel disease (IBD) is a serious disorder, and exploration of active compounds to treat it is necessary. An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata (Desv.) Spring, which contained galacturonic acid, galactose, xylose, arabinose, and rhamnose with the main chain structure of →4)-α-d-GalAp-(1→ and →6)-β-d-Galp-(1→ and the branched structure of →5)-α-l-Araf-(1→ . Animal experiments showed that compared with Model group, SUSP-4 significantly improved body weight status, disease activity index (DAI), colonic shortening, and histopathological damage, and elevated occludin and zonula occludens protein 1 (ZO-1) expression in mice induced by dextran sulfate sodium salt (DSS). 16S ribosomal RNA (rRNA) sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes. Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism, which was further confirmed by a targeted metabolism study. Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice. A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B (p-NF-κB) and cyclooxygenase-2 (COX-2) and elevating NF-E2-related factor 2 (Nrf2) levels compared with Model group. In conclusion, SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD. This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD, showing great potential for in-depth research and development applications.}, }
@article {pmid38461664, year = {2024}, author = {Wang, Y and Gao, C and Niu, W and Han, S and Qin, M and Tian, Z and Zuo, W and Xia, X and Wang, H and Li, Y}, title = {Polystyrene microplastics promote intestinal colonization of Aeromonas veronii through inducing intestinal microbiota dysbiosis.}, journal = {Journal of hazardous materials}, volume = {469}, number = {}, pages = {133976}, doi = {10.1016/j.jhazmat.2024.133976}, pmid = {38461664}, issn = {1873-3336}, mesh = {Humans ; *Microplastics/toxicity ; Polystyrenes/toxicity ; Plastics ; Aeromonas veronii ; *Gastrointestinal Microbiome ; Dysbiosis/chemically induced ; Intestines ; }, abstract = {The premise that pathogen colonized microplastics (MPs) can promote the spread of pathogens has been widely recognized, however, their role in the colonization of pathogens in a host intestine has not been fully elucidated. Here, we investigated the effect of polystyrene MPs (PS-MPs) on the colonization levels of Aeromonas veronii, a typical aquatic pathogen, in the loach (Misgurnus anguillicaudatus) intestine. Multiple types of MPs were observed to promote the intestinal colonization of A. veronii, among which PS-MPs exhibited the most significant stimulating effect (67.18% increase in A. veronii colonization). PS-MPs inflicted serious damage to the intestinal tracts of loaches and induced intestinal microbiota dysbiosis. The abundance of certain intestinal bacteria with resistance against A. veronii colonization decreased, with Lactococcus sp. showing the strongest colonization resistance (73.64% decline in A. veronii colonization). Fecal microbiota transplantation was performed, which revealed that PS-MPs induced intestinal microbiota dysbiosis was responsible for the increased colonization of A. veronii in the intestine. It was determined that PS-MPs reshaped the intestinal microbiota community to attenuate the colonization resistance against A. veronii colonization, resulting in an elevated intestinal colonization levels of A. veronii.}, }
@article {pmid38460630, year = {2024}, author = {Huang, X and Hu, X and Li, S and Li, T}, title = {Vitexin-rhamnoside encapsulated with zein-pectin nanoparticles relieved high-fat diet induced lipid metabolism disorders in mice by altering the gut microbiota.}, journal = {International journal of biological macromolecules}, volume = {264}, number = {Pt 2}, pages = {130704}, doi = {10.1016/j.ijbiomac.2024.130704}, pmid = {38460630}, issn = {1879-0003}, mesh = {Mice ; Animals ; Diet, High-Fat/adverse effects ; Lipid Metabolism ; *Zein/pharmacology ; Pectins/pharmacology ; *Gastrointestinal Microbiome ; *Lipid Metabolism Disorders ; Mice, Inbred C57BL ; *Apigenin ; }, abstract = {This study aimed to investigate the modulatory effects of Vitexin-rhamnoside (VR) and Zein-VR-pectin nanoparticles (VRN) on lipid metabolism disorders induced by high-fat diet (HFD). The ingestion of VR or VRN attenuated dyslipidemia and fat accumulation in HFD mice, and improved intestinal dysbiosis by regulating the relative abundance of dominant bacteria, alleviating chronic inflammation and hepatic injury in HFD mice. The intervention effect of VRN was significantly higher than that of VR. After fecal microbiota transplantation (FMT) treatment, the fecal microbiota of VRN-treated donor mice significantly attenuated the symptoms associated with hyperlipidemia, confirming that VRN ameliorates HFD-induced disorders of lipid metabolism by modulating the gut microbiota, especially increasing the abundance of Rombousia and Faecalibaculum. Overall, VRN can regulate the gut microbiota and thus improve lipid metabolism. The present study provided new evidence that nanoparticles enhance the bioavailability of food bioactive ingredients.}, }
@article {pmid38459479, year = {2024}, author = {Wang, Q and He, Z and Zhu, J and Hu, M and Yang, L and Yang, H}, title = {Polyphyllin B inhibited STAT3/NCOA4 pathway and restored gut microbiota to ameliorate lung tissue injury in cigarette smoke-induced mice.}, journal = {BMC biotechnology}, volume = {24}, number = {1}, pages = {13}, pmid = {38459479}, issn = {1472-6750}, support = {20C1591//Scientific Research Project of Hunan Provincial Department of Education/ ; kq2202044//Science and Technology Program Foundation of Changsha/ ; 202203022887//Scientific Research Project of Hunan Provincial Health Commission/ ; }, mesh = {Animals ; Mice ; Cell Line ; *Cigarette Smoking/adverse effects ; Ferritins/metabolism ; *Gastrointestinal Microbiome ; Inflammation/pathology ; Lipopolysaccharides/adverse effects ; Lung ; *Lung Injury/complications/metabolism/pathology ; Molecular Docking Simulation ; *Pulmonary Disease, Chronic Obstructive/therapy/drug therapy ; RNA, Ribosomal, 16S ; STAT3 Transcription Factor/genetics/metabolism ; }, abstract = {OBJECTIVE: Smoking was a major risk factor for chronic obstructive pulmonary disease (COPD). This study plan to explore the mechanism of Polyphyllin B in lung injury induced by cigarette smoke (CSE) in COPD.<br><br>METHODS: Network pharmacology and molecular docking were applied to analyze the potential binding targets for Polyphyllin B and COPD. Commercial unfiltered CSE and LPS were used to construct BEAS-2B cell injury in vitro and COPD mouse models in vivo, respectively, which were treated with Polyphyllin B or fecal microbiota transplantation (FMT). CCK8, LDH and calcein-AM were used to detect the cell proliferation, LDH level and labile iron pool. Lung histopathology, Fe[3+] deposition and mitochondrial morphology were observed by hematoxylin-eosin, Prussian blue staining and transmission electron microscope, respectively. ELISA was used to measure inflammation and oxidative stress levels in cells and lung tissues. Immunohistochemistry and immunofluorescence were applied to analyze the 4-HNE, LC3 and Ferritin expression. RT-qPCR was used to detect the expression of FcRn, pIgR, STAT3 and NCOA4. Western blot was used to detect the expression of Ferritin, p-STAT3/STAT3, NCOA4, GPX4, TLR2, TLR4 and P65 proteins. 16S rRNA gene sequencing was applied to detect the gut microbiota.<br><br>RESULTS: Polyphyllin B had a good binding affinity with STAT3 protein, which as a target gene in COPD. Polyphyllin B inhibited CS-induced oxidative stress, inflammation, mitochondrial damage, and ferritinophagy in COPD mice. 16S rRNA sequencing and FMT confirmed that Akkermansia and Escherichia_Shigella might be the potential microbiota for Polyphyllin B and FMT to improve CSE and LPS-induced COPD, which were exhausted by the antibiotics in C&#x2009;+&#x2009;L and C&#x2009;+&#x2009;L&#x2009;+&#x2009;P mice. CSE and LPS induced the decrease of cell viability and the ferritin and LC3 expression, and the increase of NCOA4 and p-STAT3 expression in BEAS-2B cells, which were inhibited by Polyphyllin B. Polyphyllin B promoted ferritin and LC3II/I expression, and inhibited p-STAT3 and NCOA4 expression in CSE&#x2009;+&#x2009;LPS-induced BEAS-2B cells.<br><br>CONCLUSION: Polyphyllin B improved gut microbiota disorder and inhibited STAT3/NCOA4 pathway to ameliorate lung tissue injury in CSE and LPS-induced mice.}, }
@article {pmid38457473, year = {2024}, author = {Ji, K and Zhang, M and Du, L and Wang, J and Liu, Y and Xu, C and He, N and Wang, Q and Gu, Y and Song, H and Wang, Y and Liu, Q}, title = {Exploring the Role of Inulin in Targeting the Gut Microbiota: An Innovative Strategy for Alleviating Colonic Fibrosis Induced By Irradiation.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {11}, pages = {5710-5724}, pmid = {38457473}, issn = {1520-5118}, mesh = {Animals ; Mice ; *Inulin/metabolism ; *Gastrointestinal Microbiome ; Fibroblasts/metabolism ; Fatty Acids, Volatile/metabolism ; Fibrosis ; }, abstract = {The use of radiation therapy to treat pelvic and abdominal cancers can lead to the development of either acute or chronic radiation enteropathy. Radiation-induced chronic colonic fibrosis is a common gastrointestinal disorder resulting from the above radiation therapy. In this study, we establish the efficacy of inulin supplements in safeguarding against colonic fibrosis caused by irradiation therapy. Studies have demonstrated that inulin supplements enhance the proliferation of bacteria responsible to produce short-chain fatty acids (SCFAs) and elevate the levels of SCFAs in feces. In a mouse model of chronic radiation enteropathy, the transplantation of gut microbiota and its metabolites from feces of inulin-treated mice were found to reduce colonic fibrosis in validation experiments. Administering inulin-derived metabolites from gut microbiota led to a notable decrease in the expression of genes linked to fibrosis and collagen production in mouse embryonic fibroblast cell line NIH/3T3. In the cell line, inulin-derived metabolites also suppressed the expression of genes linked to the extracellular matrix synthesis pathway. The results indicate a novel and practical approach to safeguarding against chronic radiation-induced colonic fibrosis.}, }
@article {pmid38457257, year = {2024}, author = {Liu, X and Li, Y and Gu, M and Xu, T and Wang, C and Chang, P}, title = {Radiation enteropathy-related depression: A neglectable course of disease by gut bacterial dysbiosis.}, journal = {Cancer medicine}, volume = {13}, number = {4}, pages = {e6865}, pmid = {38457257}, issn = {2045-7634}, support = {20200201400JC//Scientific and Technological Developing Scheme Foundation of Jilin Province/ ; 82272738//National Natural Science Foundation of China/ ; 81874254//National Natural Science Foundation of China/ ; JLSWSRCZX2020-00931//Special Foundation to Health Professionals of Jilin Province/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology ; Depression/etiology ; *Inflammatory Bowel Diseases ; Bacteria ; }, abstract = {Radiation enteropathy (RE) is common in patients treated with radiotherapy for pelvic-abdominal cancers. Accumulating data indicate that gut commensal bacteria determine intestinal radiosensitivity. Radiotherapy can result in gut bacterial dysbiosis. Gut bacterial dysbiosis contributes to the pathogenesis of RE. Mild to moderate depressive symptoms can be observed in patients with RE in clinical settings; however, the rate of these symptoms has not been reported. Studies have demonstrated that gut bacterial dysbiosis induces depression. In the state of comorbidity, RE and depression may be understood as local and abscopal manifestations of gut bacterial disorders. The ability of comorbid depression to worsen inflammatory bowel disease (IBD) has long been demonstrated and is associated with dysfunction of cholinergic neural anti-inflammatory pathways. There is a lack of direct evidence for RE comorbid with depression. It is widely accepted that RE shares similar pathophysiologic mechanisms with IBD. Therefore, we may be able to draw on the findings of the relationship between IBD and depression. This review will explore the relationship between gut bacteria, RE, and depression in light of the available evidence and indicate a method for investigating the mechanisms of RE combined with depression. We will also describe new developments in the treatment of RE with probiotics, prebiotics, and fecal microbial transplantation.}, }
@article {pmid38457115, year = {2024}, author = {Sadowsky, MJ and Matson, M and Mathai, PP and Pho, M and Staley, C and Evert, C and Weldy, M and Khoruts, A}, title = {Successful Treatment of Recurrent Clostridioides difficile Infection Using a Novel, Drinkable, Oral Formulation of Fecal Microbiota.}, journal = {Digestive diseases and sciences}, volume = {69}, number = {5}, pages = {1778-1784}, pmid = {38457115}, issn = {1573-2568}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; Animals ; Administration, Oral ; Clostridium Infections/therapy/microbiology ; Mice ; Aged ; Feces/microbiology ; Clostridioides difficile/isolation &amp; purification ; Recurrence ; Male ; Female ; Gastrointestinal Microbiome/drug effects ; Powders ; Treatment Outcome ; Aged, 80 and over ; }, abstract = {BACKGROUND: Fecal microbiota transplants can be administered orally in encapsulated form or require invasive procedures to administer liquid formulations. There is a need for an oral liquid formulation of fecal microbiota for patients who are unable to swallow capsules, especially if they require multiple, repeated administrations.<br><br>AIMS: These studies were conducted to develop a protocol to manufacture&#xa0;an organoleptically acceptable powdered fecal microbiota formulation that can be suspended in a liquid carrier and used for fecal microbiota transplantation.<br><br>METHODS: Several processing steps were investigated, including extra washes of microbiota prior to lyophilization and an addition of a flavoring agent. The viability of bacteria in the transplant formulation was tested using live/dead microscopy staining and engraftment into antibiotic-treated mice. After development of a clinical protocol for suspension of the powdered microbiota, the new formulation was tested in three elderly patients with recurrent Clostridioides difficile infections and who have difficulties in swallowing capsules. Changes in the microbial community structure in one of the patients were characterized using 16S rRNA gene profiling and engraftment analysis.<br><br>RESULTS: The processing steps used to produce an organoleptically acceptable suspension of powdered fecal microbiota did not result in loss of its viability. The powder could be easily suspended in a liquid carrier. The use of the new formulation was associated with abrogation of the cycle of C. difficile infection recurrences in the three patients.<br><br>CONCLUSION: We developed a novel organoleptically acceptable liquid formulation of fecal microbiota that is suitable for use in&#xa0;clinical trials for patients with difficulties in swallowing capsules.}, }
@article {pmid38454984, year = {2024}, author = {Lwin, MW and Cheng, CY and Calderazzo, S and Schramm, C and Schlander, M}, title = {Would initiating colorectal cancer screening from age of 45 be cost-effective in Germany? An individual-level simulation analysis.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1307427}, pmid = {38454984}, issn = {2296-2565}, mesh = {Humans ; Middle Aged ; Young Adult ; Adult ; *Cost-Effectiveness Analysis ; Cost-Benefit Analysis ; Early Detection of Cancer/methods ; *Colorectal Neoplasms/diagnosis/prevention &amp; control ; Colonoscopy ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) screening has been shown to be effective and cost-saving. However, the trend of rising incidence of early-onset CRC challenges the current national screening program solely for people ≥50 years in Germany, where extending the screening to those 45-49 years might be justified. This study aims to evaluate the cost-effectiveness of CRC screening strategies starting at 45 years in Germany.<br><br>METHOD: DECAS, an individual-level simulation model accounting for both adenoma and serrated pathways of CRC development and validated with German CRC epidemiology and screening effects, was used for the cost-effectiveness analysis. Four CRC screening strategies starting at age 45, including 10-yearly colonoscopy (COL), annual/biennial fecal immunochemical test (FIT), or the combination of the two, were compared with the current screening offer starting at age 50&#x2009;years in Germany. Three adherence scenarios were considered: perfect adherence, current adherence, and high screening adherence. For each strategy, a cohort of 100,000 individuals with average CRC risk was simulated from age 20 until 90 or death. Outcomes included CRC cases averted, prevented death, quality-adjusted life-years gained (QALYG), and total incremental costs considering both CRC treatment and screening costs. A 3% discount rate was applied and costs were in 2023 Euro.<br><br>RESULT: Initiating 10-yearly colonoscopy-only or combined FIT&#x2009;+&#x2009;COL strategies at age 45 resulted in incremental gains of 7-28 QALYs with incremental costs of &#x20ac;28,360-&#x20ac;71,759 per 1,000 individuals, compared to the current strategy. The ICER varied from &#x20ac;1,029 to &#x20ac;9,763 per QALYG, and the additional number needed for colonoscopy ranged from 129 to 885 per 1,000 individuals. Among the alternatives, a three times colonoscopy strategy starting at 45&#x2009;years of age proves to be the most effective, while the FIT-only strategy was dominated by the currently implemented strategy. The findings remained consistent across probabilistic sensitivity analyses.<br><br>CONCLUSION: The cost-effectiveness findings support initiating CRC screening at age 45 with either colonoscopy alone or combined with FIT, demonstrating substantial gains in quality-adjusted life-years with a modest increase in costs. Our findings emphasize the importance of implementing CRC screening 5&#x2009;years earlier than the current practice to achieve more significant health and economic benefits.}, }
@article {pmid38454775, year = {2024}, author = {Mortezaee, K and Majidpoor, J}, title = {Immunotherapy of Human Melanoma: Past, Present, Future.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673283943240227104122}, pmid = {38454775}, issn = {1875-533X}, abstract = {Immunotherapy with immune checkpoint inhibitors (ICIs) is a promising therapeutic schedule in advanced solid cancers. In this review, clinical trials from highly reputable journals are interpreted for safety and efficacy evaluation of the common anti-programmed death-1 (PD-1) inhibitor nivolumab and/or the most known anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitor ipilimumab in advanced melanoma. Current progress in the field of melanoma immunotherapy is the focus of this review. Solo nivolumab and combo nivolumab-ipilimumab show higher responses compared to solo ipilimumab or chemotherapy. BRAF and programmed death-ligand 1 (PDL1) expression states are seemingly not reliable biomarkers of response to ICI therapy in melanoma. Solo ipilimumab and particularly a combination of nivolumab-ipilimumab show higher adverse events (AEs) compared with solo nivolumab or chemotherapy. Besides, ICI therapy is safer in mucosal melanoma, but its efficacy is higher in the cutaneous subtype. Patients receiving combination regimens who are experiencing serious AEs can discontinue such regimens until recovery and still maintain clinical benefits. To conclude, combo nivolumab-ipilimumab represents more therapeutic advantages compared with solo nivolumab or ipilimumab, but the rate of AEs is higher for combination regimens. Resistance to combo nivolumab-ipilimumab demands the application of novel approaches to go with ICIs in melanoma immunotherapy. Immunogenic agents, alternative immune checkpoints, vaccination, oncolytic viruses, extracellular vesicles (EVs) and fecal microbiome transplantation (FMT) are novel strategies in patients developing ICI resistance.}, }
@article {pmid38454425, year = {2024}, author = {Zeng, F and Su, X and Liang, X and Liao, M and Zhong, H and Xu, J and Gou, W and Zhang, X and Shen, L and Zheng, JS and Chen, YM}, title = {Gut microbiome features and metabolites in non-alcoholic fatty liver disease among community-dwelling middle-aged and older adults.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {104}, pmid = {38454425}, issn = {1741-7015}, support = {2023A1515030155//Guangdong Basic and Applied Basic Research Foundation/ ; 81602853//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82073546//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82073529//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 2007032//the 5010 Program for Clinical Researches/ ; }, mesh = {Middle Aged ; Humans ; Animals ; Mice ; Aged ; *Non-alcoholic Fatty Liver Disease/epidemiology/metabolism ; *Gastrointestinal Microbiome ; Liver/metabolism ; Independent Living ; *Microbiota ; }, abstract = {BACKGROUND: The specific microbiota and associated metabolites linked to non-alcoholic fatty liver disease (NAFLD) are still controversial. Thus, we aimed to understand how the core gut microbiota and metabolites impact NAFLD.<br><br>METHODS: The data for the discovery cohort were collected from the Guangzhou Nutrition and Health Study (GNHS) follow-up conducted between 2014 and 2018. We collected 272 metadata points from 1546 individuals. The metadata were input into four interpretable machine learning models to identify important gut microbiota associated with NAFLD. These models were subsequently applied to two validation cohorts [the internal validation cohort (n&#x2009;=&#x2009;377), and the prospective validation cohort (n&#x2009;=&#x2009;749)] to assess generalizability. We constructed an individual microbiome risk score (MRS) based on the identified gut microbiota and conducted animal faecal microbiome transplantation experiment using faecal samples from individuals with different levels of MRS to determine the relationship between MRS and NAFLD. Additionally, we conducted targeted metabolomic sequencing of faecal samples to analyse potential metabolites.<br><br>RESULTS: Among the four machine learning models used, the lightGBM algorithm achieved the best performance. A total of 12 taxa-related features of the microbiota were selected by the lightGBM algorithm and further used to calculate the MRS. Increased MRS was positively associated with the presence of NAFLD, with odds ratio (OR) of 1.86 (1.72, 2.02) per 1-unit increase in MRS. An elevated abundance of the faecal microbiota (f__veillonellaceae) was associated with increased NAFLD risk, whereas f__rikenellaceae, f__barnesiellaceae, and s__adolescentis were associated with a decreased presence of NAFLD. Higher levels of specific gut microbiota-derived metabolites of bile acids (taurocholic acid) might be positively associated with both a higher MRS and NAFLD risk. FMT in mice further confirmed a causal association between a higher MRS and the development of NAFLD.<br><br>CONCLUSIONS: We confirmed that an alteration in the composition of the core gut microbiota might be biologically relevant to NAFLD development. Our work demonstrated the role of the microbiota in the development of NAFLD.}, }
@article {pmid38454297, year = {2024}, author = {Buldukoglu, OC and Ocal, S and Cekin, AH}, title = {Fecal microbiota transplantation as an early therapeutic option in treatment refractory Clostridioides difficile infection.}, journal = {Journal of gastroenterology and hepatology}, volume = {39}, number = {6}, pages = {1200}, doi = {10.1111/jgh.16535}, pmid = {38454297}, issn = {1440-1746}, mesh = {Humans ; Middle Aged ; Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; Treatment Outcome ; }, }
@article {pmid38453435, year = {2024}, author = {Zhuang, B and Gan, L and Liu, B and Yuan, W and Shi, M and Peng, A and Wang, L and Chen, X and Liu, T and Zhang, S and Wang, S and Gao, Q and Wang, B and Zheng, H and Liu, C and Luo, Y and Ye, H and Lin, H and Li, Y and He, Q and Zheng, F and Luo, P and Long, G and Lu, W and Li, K and Yang, J and Liu, YC and Zhang, Z and Li, X and Zhang, W and Zuo, L}, title = {Tolerability, safety and efficacy of a novel phosphate binder VS-505 (AP301): a Phase 2 dose-escalation and dose-ranging study in patients undergoing maintenance hemodialysis.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {39}, number = {10}, pages = {1649-1661}, doi = {10.1093/ndt/gfae053}, pmid = {38453435}, issn = {1460-2385}, support = {//Shanghai Alebund Pharmaceuticals Limited/ ; }, mesh = {Humans ; Male ; *Renal Dialysis/adverse effects ; Female ; Middle Aged ; *Hyperphosphatemia/drug therapy/etiology ; Aged ; *Chelating Agents/administration &amp; dosage/therapeutic use/adverse effects ; Dose-Response Relationship, Drug ; Adult ; Phosphates/blood ; Ferric Compounds/administration &amp; dosage/adverse effects/therapeutic use ; Sevelamer/administration &amp; dosage/therapeutic use ; Follow-Up Studies ; Kidney Failure, Chronic/therapy/complications ; Renal Insufficiency, Chronic/therapy/complications ; }, abstract = {BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part Phase 2 study evaluated the tolerability, safety and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD).<br><br>METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50 and 9.00&#xa0;g/day for 2&#xa0;weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50 or 6.75&#xa0;g/day) or sevelamer carbonate 4.80&#xa0;g/day for 6&#xa0;weeks. The primary efficacy endpoint was the change in serum phosphorus.<br><br>RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during Weeks 1-2 of treatment). Most gastrointestinal disorders resolved without intervention, and none was serious. In Part 1, serum phosphorus significantly improved (mean change -2.0&#xa0;mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75&#xa0;g/day, and sevelamer carbonate 4.80&#xa0;g/day [mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2) and -1.4 (-2.2, -0.5) mg/dL, respectively]. In both parts, serum phosphorus reductions occurred within 1&#xa0;week of VS-505 initiation, returning to baseline within 2&#xa0;weeks of VS-505 discontinuation.<br><br>CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD.<br><br>NCT04551300&#x2009;.}, }
@article {pmid38452932, year = {2024}, author = {Zhang, D and Lv, W and Xu, Y and Zhang, Z and Zeng, S and Zhang, W and Gong, L and Shao, L and Zhang, M and He, T and Liu, Y and Wang, Y and Liu, L and Hu, X}, title = {Microbial bile acid metabolite ameliorates mycophenolate mofetil-induced gastrointestinal toxicity through vitamin D3 receptor.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {24}, number = {7}, pages = {1132-1145}, doi = {10.1016/j.ajt.2024.02.029}, pmid = {38452932}, issn = {1600-6143}, mesh = {Animals ; *Mycophenolic Acid/pharmacology ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Receptors, Calcitriol/metabolism ; *Bile Acids and Salts/metabolism ; Immunosuppressive Agents ; Mice, Inbred C57BL ; Male ; Gastrointestinal Diseases/chemically induced ; Lithocholic Acid ; Humans ; }, abstract = {Mycophenolate mofetil (MMF) is one of the most used immunosuppressive drugs in organ transplantation, but frequent gastrointestinal (GI) side effects through unknown mechanisms limit its clinical use. Gut microbiota and its metabolites were recently reported to play a vital role in MMF-induced GI toxicity, but the specific mechanism of how they interact with the human body is still unclear. Here, we found that secondary bile acids (BAs), as bacterial metabolites, were significantly reduced by MMF administration in the gut of mice. Microbiome data and fecal microbiota transfer model supported a microbiota-dependent effect on the reduction of secondary BAs. Supplementation of the secondary BA lithocholic acid alleviated MMF-induced weight loss, colonic inflammation, and oxidative phosphorylation damage. Genetic deletion of the vitamin D3 receptor (VDR), which serves as a primary colonic BA receptor, in colonic epithelial cells (VDR[ΔIEC]) abolished the therapeutic effect of lithocholic acid on MMF-induced GI toxicity. Impressively, we discovered that paricalcitol, a Food and Drug Administration-approved VDR agonist that has been used in clinics for years, could effectively alleviate MMF-induced GI toxicity. Our study reveals a previously unrecognized mechanism of gut microbiota, BAs, and VDR signaling in MMF-induced GI side effects, offering potential therapeutic strategies for clinics.}, }
@article {pmid38449863, year = {2024}, author = {Hediyal, TA and Vichitra, C and Anand, N and Bhaskaran, M and Essa, SM and Kumar, P and Qoronfleh, MW and Akbar, M and Kaul-Ghanekar, R and Mahalakshmi, AM and Yang, J and Song, BJ and Monaghan, TM and Sakharkar, MK and Chidambaram, SB}, title = {Protective effects of fecal microbiota transplantation against ischemic stroke and other neurological disorders: an update.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1324018}, pmid = {38449863}, issn = {1664-3224}, mesh = {Humans ; *Ischemic Stroke ; Fecal Microbiota Transplantation ; *Nervous System Diseases/therapy ; *Stroke/therapy ; *Parkinson Disease ; }, abstract = {The bidirectional communication between the gut and brain or gut-brain axis is regulated by several gut microbes and microbial derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides. The Gut microbiota (GM) produce neuroactives, specifically neurotransmitters that modulates local and central neuronal brain functions. An imbalance between intestinal commensals and pathobionts leads to a disruption in the gut microbiota or dysbiosis, which affects intestinal barrier integrity and gut-immune and neuroimmune systems. Currently, fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection. FMT elicits its action by ameliorating inflammatory responses through the restoration of microbial composition and functionality. Thus, FMT may be a potential therapeutic option in suppressing neuroinflammation in post-stroke conditions and other neurological disorders involving the neuroimmune axis. Specifically, FMT protects against ischemic injury by decreasing IL-17, IFN-γ, Bax, and increasing Bcl-2 expression. Interestingly, FMT improves cognitive function by lowering amyloid-β accumulation and upregulating synaptic marker (PSD-95, synapsin-1) expression in Alzheimer's disease. In Parkinson's disease, FMT was shown to inhibit the expression of TLR4 and NF-κB. In this review article, we have summarized the potential sources and methods of administration of FMT and its impact on neuroimmune and cognitive functions. We also provide a comprehensive update on the beneficial effects of FMT in various neurological disorders by undertaking a detailed interrogation of the preclinical and clinical published literature.}, }
@article {pmid38449416, year = {2024}, author = {Yuki, H and Okazaki, M and Katano, K and Sugita, A and Tokoro, T and Gabata, R and Takada, S and Nakanuma, S and Makino, I and Yagi, S}, title = {[Two Cases of Portal Vein Stent Placement for Portal Vein Stenosis Due to Recurrence of Pancreatic Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {51}, number = {2}, pages = {211-213}, pmid = {38449416}, issn = {0385-0684}, mesh = {Female ; Humans ; Aged ; Portal Vein/surgery ; Constriction, Pathologic/etiology/surgery ; *Pancreatic Neoplasms/complications/surgery ; Pancreas ; Melena ; *Anemia ; }, abstract = {We report 2 cases of portal vein stent placement for malignant portal stenosis due to recurrence of pancreatic cancer with symptoms of portal hypertension. Case 1: The patient was a 68-year-old female. Five years ago, a mass was found around the aorta on a computerized tomography(CT)scan taken after a residual pancreatectomy for pancreatic cancer. It was diagnosed as lymph node recurrence and S-1 therapy was started. As further tumor enlargement led to portal vein compression, venostasis around the ascending jejunum, anemia, and black stools, a portal vein stent was placed. The portal vein blood flow was improved, the collateral vessels disappeared, and the patient no longer experienced anemia or black stool. Case 2: A 75-year-old female patient underwent a subtotal gastric-sparing pancreaticoduodenectomy and combined resection of the portal vein for pancreas head cancer. On a postoperative CT scan taken 6 months later, a mass compressing the portal vein appeared, which was diagnosed as a local recurrence. As thrombocytopenia was observed, a portal vein stent was placed before starting chemotherapy. The portal vein blood flow and the platelet count improved. Portal vein stenting is an effective procedure for malignant portal stenosis, improving portal blood flow and clinical symptoms.}, }
@article {pmid38447617, year = {2024}, author = {Cai, J and Zhu, Z and Li, Y and Li, Q and Tian, T and Meng, Q and Wang, T and Ma, Y and Wu, J}, title = {Artemisia capillaris Thunb. Polysaccharide alleviates cholestatic liver injury through gut microbiota modulation and Nrf2 signaling pathway activation in mice.}, journal = {Journal of ethnopharmacology}, volume = {327}, number = {}, pages = {118009}, doi = {10.1016/j.jep.2024.118009}, pmid = {38447617}, issn = {1872-7573}, mesh = {Mice ; Animals ; NF-E2-Related Factor 2/metabolism ; *Gastrointestinal Microbiome ; *Artemisia ; Liver ; *Cholestasis/chemically induced ; Signal Transduction ; *Jaundice/metabolism ; Bile Acids and Salts/metabolism ; }, abstract = {According to traditional Chinese medicine (TCM) theory, cholestasis belongs to category of jaundice. Artemisia capillaris Thunb. has been widely used for the treatment of jaundice in TCM. The polysaccharides are the one of main active components of the herb, but its effects on cholestasis remain unclear.<br><br>AIM OF THE STUDY: To investigate the protective effect and mechanism of Artemisia capillaris Thunb. polysaccharide (APS) on cholestasis and liver injury.<br><br>MATERIALS AND METHODS: The amelioration of APS on cholestasis was evaluated in an alpha-naphthyl isothiocyanate (ANIT)-induced mice model. Then nuclear Nrf2 knockout mice, mass spectrometry, 16s rDNA sequencing, metabolomics, and molecular biotechnology methods were used to elucidate the associated mechanisms of APS against cholestatic liver injury.<br><br>RESULTS: Treatment with low and high doses of APS markedly decreased cholestatic liver injury of mice. Mechanistically, APS promoted nuclear translocation of hepatic nuclear factor erythroid 2-related factor (Nrf2), upregulated downstream bile acid (BA) efflux transporters and detoxifying enzymes expression, improved BA homeostasis, and attenuated oxidative liver injury; however, these effects were annulled in Nrf2 knock-out mice. Furthermore, APS ameliorated the microbiota dysbiosis of cholestatic mice and selectively increased short-chain fatty acid (SCFA)-producing bacteria growth. Fecal microbiota transplantation of APS also promoted hepatic Nrf2 activation, increased BA efflux transporters and detoxifying enzymes expression, ameliorated intrahepatic BA accumulation and cholestatic liver injury. Non-targeted metabolomics and in vitro microbiota culture confirmed that APS significantly increased the production of a microbiota-derived SCFA (butyric acid), which is also able to upregulate Nrf2 expression.<br><br>CONCLUSIONS: These findings indicate that APS can ameliorate cholestasis by modulating gut microbiota and activating the Nrf2 pathway, representing a novel therapeutic approach for cholestatic liver disease.}, }
@article {pmid38446328, year = {2024}, author = {Olejnik, P and Buczma, K and Cudnoch-Jędrzejewska, A and Kasarełło, K}, title = {Involvement of gut microbiota in multiple sclerosis-review of a new pathophysiological hypothesis and potential treatment target.}, journal = {Immunologic research}, volume = {72}, number = {4}, pages = {554-565}, pmid = {38446328}, issn = {1559-0755}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Multiple Sclerosis/immunology/microbiology/therapy ; Animals ; *Dysbiosis/immunology ; *Probiotics/therapeutic use/administration &amp; dosage ; *Fecal Microbiota Transplantation ; Blood-Brain Barrier/immunology/metabolism ; Fatty Acids, Volatile/metabolism ; }, abstract = {Multiple sclerosis (MS) is a chronic inflammatory disease that leads to demyelination and damage to the central nervous system. It is well known, the significance of the involvement and influence of the immune system in the development and course of MS. Nowadays, more and more studies are demonstrating that an important factor that affects the action of the immune system is the gut microbiota. Changes in the composition and interrelationships in the gut microbiota have a significant impact on the course of MS. Dysbiosis affects the disease course mainly by influencing the immune system directly but also by modifying the secreted metabolites and increasing mucosal permeability. The essential metabolites affecting the course of MS are short-chain fatty acids, which alter pro- and anti-inflammatory responses in the immune system but also increase the permeability of the intestinal wall and the blood-brain barrier. Dietary modification alone can have a significant impact on MS. Based on these interactions, new treatments for MS are being developed, including probiotics administration, supplementation of bacterial metabolites, fecal microbiota transplantation, and dietary changes. Further studies may serve to develop new drugs and therapeutic approaches for MS.}, }
@article {pmid38446309, year = {2024}, author = {El-Salhy, M and Hatlebakk, JG}, title = {Factors Underlying the Difference in Response to Fecal Microbiota Transplantation Between IBS Patients with Severe and Moderate Symptoms.}, journal = {Digestive diseases and sciences}, volume = {69}, number = {4}, pages = {1336-1344}, pmid = {38446309}, issn = {1573-2568}, mesh = {Humans ; Duodenum ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; *Irritable Bowel Syndrome/diagnosis ; Treatment Outcome ; }, abstract = {BACKGROUND: Previous studies showed that patients with Severe IBS respond better to fecal microbiota transplantation (FMT) than do those with Moderate IBS.<br><br>AIMS: The present study aimed to determine the effects of the transplant dose, route of administering it and repeating FMT on this difference.<br><br>METHODS: This study included 186 patients with IBS randomized 1:1:1 into groups with a 90-g transplant administered once to the colon (LI), once to the duodenum (SI), or twice to the distal duodenum twice (repeated SI). The patients provided a fecal sample and were asked to complete three questionnaires at baseline and at 3, 6, and 12 months after FMT. The fecal bacteria composition and Dysbiosis index were analyzed using 16&#xa0;S rRNA gene PCR DNA amplification/probe hybridization covering regions V3-V9.<br><br>RESULTS: There was no difference in the response rates between severe IBS and moderate IBS for SI and repeated SI at all observation intervals after FMT. In the LI group, the response rate at 3 months after FMT was higher for moderate IBS than for severe IBS. The levels of Dorea spp. were higher and those of Streptococcus salivarius subsp. Thermophilus, Alistipes spp., Bacteroides and Prevotella spp., Parabacteroides johnsoni and Parabacteroides spp. were lower in moderate IBS than in severe IBS.<br><br>CONCLUSIONS: There was no difference in the response to FMT between severe and moderate IBS when a 90-g transplant was administered to the small intestine. The difference in the bacterial profile between severe and moderate IBS may explain the difference in symptoms between these patients. (www.<br><br>CLINICALTRIALS: gov : NCT04236843).}, }
@article {pmid38444807, year = {2024}, author = {Ye, W and Fan, J and Wu, W and Chen, Z and Huang, Q and Qian, L}, title = {Effects of fecal microbiota transplantation on metabolic health of DBA mice.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1352555}, pmid = {38444807}, issn = {1664-302X}, abstract = {INTRODUCTION: Numerous studies have demonstrated that C57BL/6 mice exhibit superior growth rates and overall growth performance compared to DBA mice. To investigate whether this discrepancy in growth performance is linked to the composition of gut microorganisms, we conducted fecal microbiome transplantation (FMT) experiments.<br><br>METHODS: Specifically, we transplanted fecal fluids from adult C57BL/6 mice, high-fat C57BL/6 mice, and Wistar rats into weaned DBA mice (0.2mL/d), and subsequently analyzed their gut contents and gene expression through 16S rRNA sequencing and transcriptome sequencing. During the test period, C57BL/6 mice and Wistar rats were provided with a normal diet, and high-fat C57BL/6 mice were provided with a high-fat diet.<br><br>RESULTS: The results of our study revealed that mice receiving FMT from all three donor groups exhibited significantly higher daily weight gain and serum triglyceride (TG) levels compared to mice of CK group. 16S rRNA sequensing unveiled substantial differences in the abundance and function of the gut microbiota between the FMT groups and the CK group. Transcriptome analysis revealed a total of 988 differential genes, consisting of 759 up-regulated genes and 187 down-regulated genes, between the three experimental groups and the CK group. Functional Gene Ontology (GO) annotation suggested that these genes were primarily linked to lipid metabolism, coagulation, and immunity. Pearson correlation analysis was performed on the differential genes and clusters, and it revealed significant correlations, mainly related to processes such as fatty acid metabolism, fat digestion and absorption, and cholesterol metabolism.<br><br>DISCUSSION: In summary, FMT from dominant strains improved the growth performance of DBA mice, including body weight gain, institutional growth, and immune performance. This change may be due to the increase of probiotic content in the intestinal tract by FMT and subsequent alteration of intestinal gene expression. However, the effects of cross-species fecal transplantation on the intestinal flora and gene expression of recipient mice were not significant.}, }
@article {pmid38441806, year = {2024}, author = {Blair, HA}, title = {SER-109 (VOWST[™]): A Review in the Prevention of Recurrent Clostridioides difficile Infection.}, journal = {Drugs}, volume = {84}, number = {3}, pages = {329-336}, pmid = {38441806}, issn = {1179-1950}, mesh = {Adult ; Humans ; Adolescent ; Quality of Life ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy/prevention &amp; control ; Gastrointestinal Tract ; Recurrence ; Fecal Microbiota Transplantation ; }, abstract = {SER-109 (VOWST[™]; fecal microbiota spores, live-brpk) is a live biotherapeutic product indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in patients 18 years of age and older following standard of care (SOC) antibacterial treatment for recurrent CDI. It is a purified bacterial spore suspension sourced from healthy donors. As the first oral faecal microbiota product approved for prevention of recurrent CDI, SER-109 is administered as four capsules once daily for three consecutive days. In a well-designed, placebo-controlled, phase III trial (ECOSPOR III), SER-109 significantly reduced the risk of recurrent CDI at 8 weeks post-treatment, with a durable response seen at 6 months post-treatment. Treatment with SER-109 was also associated with rapid and steady improvement in health-related quality of life compared with placebo. SER-109 was generally well tolerated, with a safety profile similar to that of placebo. The most common adverse events were of mild to moderate severity and generally gastrointestinal in nature. Thus, with the convenience of oral administration and lack of necessity for cold storage, SER-109 is a valuable option for preventing further CDI recurrence in adults following antibacterial treatment for recurrent CDI.}, }
@article {pmid38441196, year = {2024}, author = {Oldereid, TS and Jiang, X and Nordhus, KS and Ponzetta, A and Bjørnholt, JV and Björkström, NK and Melum, E and Rasmussen, H}, title = {Role of bacteria and microbial metabolites in immune modulation during early life.}, journal = {Scandinavian journal of immunology}, volume = {99}, number = {2}, pages = {e13336}, doi = {10.1111/sji.13336}, pmid = {38441196}, issn = {1365-3083}, support = {//Helse S&#xf8;r-&#xd8;st RHF/ ; //Norwegian PSC Research Center/ ; //Research Support Services, Oslo University Hospital/ ; }, mesh = {Animals ; Mice ; *Sodium Chloride ; Administration, Oral ; *B-Lymphocytes ; Bacteria ; Feces ; }, abstract = {Host-microbiome interplay from birth is essential for immune imprinting and tuning. Live gut microbes and microbial-derived metabolites regulate the development and modulation of the immune system, but whether microbial metabolites solely are sufficient to induce immune maturation remains unclear. Sterile faecal filtrates (FFT) were generated from murine gut contents. Newborn germ-free (GF) mice were treated twice daily with FFT (GF-FFT) or saline (GF-NaCl) from post-natal day 5 until 4 weeks of age. A third group of GF neonates were conventionalized by the transfer of caecal microbiota with live gut microbes. Host immune compartments were comprehensively immunophenotyped and systemically analysed in all available immune-related organs using flow cytometry. Oral FFT was associated with reduced survival among neonates (n = 7/19; 36.8% mortality), while saline treatment was well tolerated (n = 1/17, 5.9% mortality). Four-week-old FFT-treated pups were comparable in body weight to GF-NaCl, and the major B-cell, conventional T-cell and unconventional T-cell subsets were unchanged from saline-treated mice. Live bacteria administered during early life induced clear changes in proportions of B cells, T cells and T-cell subsets in all mucosal tissues and secondary lymphoid organs compared to GF-FFT, including restoration of intestinal natural killer T (NKT) cells with characteristics similar to conventional pups. Our findings show that oral administration of a FFT made of microbial metabolites, antigens and bacteriophages alone is insufficient to induce normal immune development elicited by the presence of live bacteria. Reduced survival during neonatal FFT treatment suggests a potential bioactive attribute of sterile faecal filtrates.}, }
@article {pmid38439546, year = {2024}, author = {Madhav, A and Bousfield, R and Pereira-Dias, J and Cormie, C and Forrest, S and Keane, J and Kermack, L and Higginson, E and Dougan, G and Spiers, H and Massey, D and Sharkey, L and Rutter, C and Woodward, J and Russell, N and Amin, I and Butler, A and Atkinson, K and Dymond, T and Bartholdson Scott, J and Baker, S and Gkrania-Klotsas, E}, title = {A metagenomic prospective cohort study on gut microbiome composition and clinical infection in small bowel transplantation.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2323232}, pmid = {38439546}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Metagenome ; Prospective Studies ; *Sepsis ; *Microbiota ; }, abstract = {Two-thirds of small-bowel transplantation (SBT) recipients develop bacteremia, with the majority of infections occurring within 3 months post-transplant. Sepsis-related mortality occurs in 31% of patients and is commonly caused by bacteria of gut origin, which are thought to translocate across the implanted organ. Serial post-transplant surveillance endoscopies provide an opportunity to study whether the composition of the ileal and colonic microbiota can predict the emergence as well as the pathogen of subsequent clinical infections in the SBT patient population. Five participants serially underwent aspiration of ileal and colonic bowel effluents at transplantation and during follow-up endoscopy either until death or for up to 3 months post-SBT. We performed whole-metagenome sequencing (WMS) of 40 bowel effluent samples and compared the results with clinical infection episodes. Microbiome composition was concordant between participants and timepoint-matched ileal and colonic samples. Four out of five (4/5) participants had clinically significant infections thought to be of gut origin. Bacterial translocation from the gut was observed in 3/5 patients with bacterial infectious etiologies. In all three cases, the pathogens had demonstrably colonized the gut between 1-10 days prior to invasive clinical infection. Recipients with better outcomes received donor grafts with higher alpha diversity. There was an increase in the number of antimicrobial resistance genes associated with longer hospital stay for all participants. This metagenomic study provides preliminary evidence to support the pathogen translocation hypothesis of gut-origin sepsis in the SBT cohort. Ileal and colonic microbiome compositions were concordant; therefore, fecal metagenomic analysis could be a useful surveillance tool for impeding infection with specific gut-residing pathogens.}, }
@article {pmid38436067, year = {2024}, author = {Zhang, L and Liu, Z and Zhang, W and Wang, J and Kang, H and Jing, J and Han, L and Gao, A}, title = {Gut microbiota-palmitoleic acid-interleukin-5 axis orchestrates benzene-induced hematopoietic toxicity.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2323227}, pmid = {38436067}, issn = {1949-0984}, mesh = {Animals ; Mice ; Mice, Inbred C57BL ; *Interleukin-5 ; Benzene/toxicity ; *Gastrointestinal Microbiome ; Fatty Acids ; Inflammation ; *Fatty Acids, Monounsaturated ; }, abstract = {Due to the annual increase in its production and consumption in occupational environments, the adverse blood outcomes caused by benzene are of concern. However, the mechanism of benzene-induced hematopoietic damage remains elusive. Here, we report that benzene exposure causes hematopoietic damage in a dose-dependent manner and is associated with disturbances in gut microbiota-long chain fatty acids (LCFAs)-inflammation axis. C57BL/6J mice exposed to benzene for 45 days were found to have a significant reduction in whole blood cells and the suppression of hematopoiesis, an increase in Bacteroides acidifaciens and a decrease in Lactobacillus murinus. Recipient mice transplanted with fecal microbiota from benzene-exposed mice showed potential for hematopoietic disruption, LCFAs, and interleukin-5 (IL-5) elevation. Abnormally elevated plasma LCFAs, especially palmitoleic acid (POA) exacerbated benzene-induced immune-inflammation and hematopoietic damage via carnitine palmitoyltransferase 2 (CPT2)-mediated disorder of fatty acid oxidation. Notably, oral administration of probiotics protects the mice against benzene-induced hematopoietic toxicity. In summary, our data reveal that the gut microbiota-POA-IL-5 axis is engaged in benzene-induced hematopoietic damage. Probiotics might be a promising candidate to prevent hematopoietic abnormalities from benzene exposure.}, }
@article {pmid38435309, year = {2024}, author = {Tang, F and Deng, M and Xu, C and Yang, R and Ji, X and Hao, M and Wang, Y and Tian, M and Geng, Y and Miao, J}, title = {Unraveling the microbial puzzle: exploring the intricate role of gut microbiota in endometriosis pathogenesis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1328419}, pmid = {38435309}, issn = {2235-2988}, mesh = {Female ; Humans ; *Gastrointestinal Microbiome ; *Endometriosis/etiology ; *Microbiota ; Estrogens ; Inflammation ; }, abstract = {Endometriosis (EMs) is a prevalent gynecological disorder characterized by the growth of uterine tissue outside the uterine cavity, causing debilitating symptoms and infertility. Despite its prevalence, the exact mechanisms behind EMs development remain incompletely understood. This article presents a comprehensive overview of the relationship between gut microbiota imbalance and EMs pathogenesis. Recent research indicates that gut microbiota plays a pivotal role in various aspects of EMs, including immune regulation, generation of inflammatory factors, angiopoietin release, hormonal regulation, and endotoxin production. Dysbiosis of gut microbiota can disrupt immune responses, leading to inflammation and impaired immune clearance of endometrial fragments, resulting in the development of endometriotic lesions. The dysregulated microbiota can contribute to the release of lipopolysaccharide (LPS), triggering chronic inflammation and promoting ectopic endometrial adhesion, invasion, and angiogenesis. Furthermore, gut microbiota involvement in estrogen metabolism affects estrogen levels, which are directly related to EMs development. The review also highlights the potential of gut microbiota as a diagnostic tool and therapeutic target for EMs. Interventions such as fecal microbiota transplantation (FMT) and the use of gut microbiota preparations have demonstrated promising effects in reducing EMs symptoms. Despite the progress made, further research is needed to unravel the intricate interactions between gut microbiota and EMs, paving the way for more effective prevention and treatment strategies for this challenging condition.}, }
@article {pmid38431789, year = {2024}, author = {Hendrickx, T and Peetermans, M and D'Hoore, A and Claes, K and Van Hootegem, A and Sabino, J}, title = {STEC colitis mimicking acute severe colitis with life-threatening consequences: a case report.}, journal = {Acta gastro-enterologica Belgica}, volume = {87}, number = {1}, pages = {37-39}, doi = {10.51821/87.1.11652}, pmid = {38431789}, issn = {1784-3227}, mesh = {Humans ; *Shiga-Toxigenic Escherichia coli ; *Escherichia coli Infections/complications/diagnosis ; *Colitis, Ulcerative/complications/diagnosis ; *Hemolytic-Uremic Syndrome/diagnosis/complications ; *Colitis/diagnosis ; }, abstract = {Acute colitis is a common feature of infection with Shiga-toxin producing Escherichia coli (STEC) and can mimic acute severe ulcerative colitis. Early recognition is important as there is a risk of developing Shiga toxin-induced haemolytic uremic syndrome (STEC-HUS), defined by the triad of microangiopathic haemolytic anemia, thrombocytopenia and organ damage. In severe cases STEC-HUS can cause severe neurological complications and can be fatal. We present a patient with a medical history of refractory ulcerative colitis, where making the diagnosis of STEC-HUS was challenging since the initial clinical presentation was difficult to differentiate from a flare of ulcerative colitis. This case illustrates that STEC induced colitis can mimic acute severe ulcerative colitis. This finding is of utmost clinical importance because of the potential life-threatening complications of STEC-HUS. Therefore it should be excluded promptly in patients with acute severe ulcerative colitis by using multiplex-PCR assay on a faecal sample.}, }
@article {pmid38430889, year = {2024}, author = {Wang, W and Fan, J and Zhang, C and Huang, Y and Chen, Y and Fu, S and Wu, J}, title = {Targeted modulation of gut and intra-tumor microbiota to improve the quality of immune checkpoint inhibitor responses.}, journal = {Microbiological research}, volume = {282}, number = {}, pages = {127668}, doi = {10.1016/j.micres.2024.127668}, pmid = {38430889}, issn = {1618-0623}, mesh = {Humans ; Immune Checkpoint Inhibitors/therapeutic use ; *Microbiota ; *Gastrointestinal Microbiome ; Cloning, Molecular ; *Neoplasms/therapy ; Tumor Microenvironment ; }, abstract = {Immune checkpoint inhibitor (ICI) therapies, such as those blocking the interaction of PD-1 with its ligands, can restore the immune-killing function of T cells. However, ICI therapy is clinically beneficial in only a small number of patients, and it is difficult to predict post-treatment outcomes, thereby limiting its widespread clinical use. Research suggests that gut microbiota can regulate the host immune system and affect cancer progression and treatment. Moreover, the effectiveness of immunotherapy is related to the composition of the patient's gut microbiota; different gut microbial strains can either activate or inhibit the immune response. However, the importance of the microbial composition within the tumor has not been explored until recently. This study describes recent advances in the crosstalk between microbes in tumors and gut microbiota, which can modulate the tumor microbiome by directly translocating into the tumor and altering the tumor microenvironment. This study focused on the potential manipulation of the tumor and gut microbiota using fecal microbiota transplantation (FMT), probiotics, antimicrobials, prebiotics, and postbiotics to enrich immune-boosting bacteria while decreasing unfavorable bacteria to proactively improve the efficacy of ICI treatments. In addition, the use of genetic technologies and nanomaterials to modify microorganisms can largely optimize tumor immunotherapy and advance personalized and precise cancer treatment.}, }
@article {pmid38428658, year = {2024}, author = {Hu, Y and Tang, J and Xie, Y and Xu, W and Zhu, W and Xia, L and Fang, J and Yu, D and Liu, J and Zheng, Z and Zhou, Q and Shou, Q and Zhang, W}, title = {Gegen Qinlian decoction ameliorates TNBS-induced ulcerative colitis by regulating Th2/Th1 and Tregs/Th17 cells balance, inhibiting NLRP3 inflammasome activation and reshaping gut microbiota.}, journal = {Journal of ethnopharmacology}, volume = {328}, number = {}, pages = {117956}, doi = {10.1016/j.jep.2024.117956}, pmid = {38428658}, issn = {1872-7573}, mesh = {Humans ; Mice ; Animals ; *Colitis, Ulcerative/chemically induced/drug therapy ; *Drugs, Chinese Herbal/adverse effects ; Inflammasomes/metabolism ; Interleukin-18/metabolism/pharmacology/therapeutic use ; *Gastrointestinal Microbiome ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Th17 Cells ; Occludin/metabolism ; RNA, Ribosomal, 16S/metabolism ; Mice, Inbred CBA ; *Colitis/drug therapy ; Cytokines/metabolism ; Trinitrobenzenes/metabolism/pharmacology/therapeutic use ; Anti-Inflammatory Agents/pharmacology ; Body Weight ; Caspases/metabolism ; Disease Models, Animal ; Colon ; }, abstract = {Chinese herbal medicine Gegen Qinlian Decoction (GQD) has been clinically shown to be an effective treatment of ulcerative colitis (UC) in China. However, the underlying mechanism of GQD's anti-ulcerative colitis properties and its effect on gut microbiota still deserve further exploration.<br><br>AIM OF THE STUDY: This study observed the regulatory effects of GQD on Th2/Th1 and Tregs/Th17&#xa0;cells balance, the NOD-like receptor family pyrin domain containing 3 (NLRP3) infammasome and gut microbiota in TNBS-induced UC in BALB/c mice.<br><br>MATERIALS AND METHODS: 61 main chemical compounds in the GQD were determined by UPLC-Q-TOF/MS. The UC BALB/c model was established by intrarectal administration of trinitrobenzene sulfonic acid (TNBS), and GQD was orally administered at low and high dosages of 2.96 and 11.83&#xa0;g/kg/day, respectively. The anti-inflammatory effects of GQD for ulcerative colitis were evaluated by survival rate, body weight, disease activity index (DAI) score, colonic weight and index, spleen index, hematoxylin-eosin (HE) staining and histopathological scores. Flow cytometry was used to detect the percentage of CD4, Th1, Th2, Th17 and Tregs cells. The levels of Th1-/Th2-/Th17-/Tregs-related inflammatory cytokines and additional proinflammatory cytokines (IL-1&#x3b2;, IL-18) were detected by CBA, ELISA, and RT-PCR. The expressions of GATA3, T-bet, NLRP3, Caspase-1, IL-I&#x3b2;, Occludin and Zonula occludens-1 (ZO-1) on colon tissues were detected by Western blot and RT-PCR. Transcriptome sequencing was performed using colon tissue and 16S rRNA gene sequencing was performed on intestinal contents. Fecal microbiota transplantation (FMT) was employed to assess the contribution of intestinal microbiota and its correlation with CD4 T cells and the NLRP3 inflammasome.<br><br>RESULTS: GQD increased the survival rate of TNBS-induced UC in BALB/c mice, and significantly improved their body weight, DAI score, colonic weight and index, spleen index, and histological characteristics. The intestinal barrier dysfunction was repaired after GQD administration through promoting the expression of tight junction proteins (Occludin and ZO-1). GQD restored the balance of Th2/Th1 and Tregs/Th17&#xa0;cells immune response of colitis mice, primarily inhibiting the increase in Th2/Th1 ratio and their transcription factor production (GATA3 and T-bet). Morever, GQD changed the secretion of Th1-/Th2-/Th17-/Tregs-related cytokines (IL-2, IL-12, IL-5, IL-13, IL-6, IL-10, and IL-17A) and reduced the expressions of IL-1&#x3b2;, IL-18. Transcriptome results suggested that GQD could also remodel the immune inflammatory response of colitis by inhibiting NOD-like receptor signaling pathway, and Western blot, immunohistochemistry and RT-PCR further revealed that GQD exerted anti-inflammatory effects by inhibiting the NLRP3 inflammasome, such as down-regulating the expression of NLRP3, Caspase-1 and IL-1&#x3b2;. More interestingly, GQD regulated gut microbiota dysbiosis, suppressed the overgrowth of conditional pathogenic gut bacteria like Helicobacter, Proteobacteria, and Mucispirillum, while the probiotic gut microbiota, such as Lactobacillus, Muribaculaceae, Ruminiclostridium_6, Akkermansia, and Ruminococcaceae_unclassified were increased. We further confirmed that GQD-treated gut microbiota was sufficient to relieve TNBS-induced colitis by FMT, involving the modulation of Th2/Th1 and Tregs/Th17 balance, inhibition of NLRP3 inflammasome activation, and enhancement of colonic barrier function.<br><br>CONCLUSIONS: GQD might alleviate TNBS-induced UC via regulating Th2/Th1 and Tregs/Th17 cells Balance, inhibiting NLRP3 inflammasome and reshaping gut microbiota, which may provide a novel strategy for patients with colitis.}, }
@article {pmid38428648, year = {2024}, author = {Ma, X and Kim, JK and Shin, YJ and Park, HS and Lee, DY and Yim, SV and Kim, DH}, title = {Lipopolysaccharide-producing Veillonella infantium and Escherichia fergusonii cause vagus nerve-mediated cognitive impairment in mice.}, journal = {Brain, behavior, and immunity}, volume = {118}, number = {}, pages = {136-148}, doi = {10.1016/j.bbi.2024.02.031}, pmid = {38428648}, issn = {1090-2139}, mesh = {Humans ; Mice ; Animals ; *Lipopolysaccharides/pharmacology ; NF-kappa B/metabolism ; Brain-Derived Neurotrophic Factor ; Tumor Necrosis Factor-alpha/metabolism ; Neuroinflammatory Diseases ; Caco-2 Cells ; *Cognitive Dysfunction ; Vagus Nerve ; Mice, Inbred C57BL ; *Escherichia ; *Veillonella ; }, abstract = {Gut microbiota communicates bidirectionally with the brain through the nervous, immune, and endocrine systems of the gut. In our preliminary study, the fecal microbiota of volunteers with mild cognitive impairment (Fmci) exhibited a higher abundance of Escherichia fergusonii (NK2001), Veillonella infantium (NK2002), and Enterococcus faecium (NK2003) populations compared with those of healthy volunteers. Therefore, we examined the effects of Fmci, NK2001 (gram-negative), NK2002 (gram-negative-like), and NK2003 (gram-positive) on cognitive impairment-like behavior, neuroinflammation, and colitis in mice with or without antibiotics. Fmci transplantation increased cognitive impairment-like behavior, hippocampal tumor necrosis factor (TNF)-α expression, and the size of toll-like receptor (TLR)4[+]Iba1[+], TLR2[+]Iba1[+], and NF-κB[+]Iba1[+] cell populations independent of antibiotic treatment. Oral gavage of NK2001, NK2002, or NK2003, which induced TNF-α expression in Caco-2 cells, significantly increased cognitive impairment-like behavior and hippocampal TNF-α expression and Iba1-positive cell populations and decreased brain-derived neurotrophic factor (BDNF) expression in mice. Celiac vagotomy significantly decreased NK2001- or NK2002-induced cognitive impairment-like behavior and hippocampal Iba1[+] cell population and TNF-α expression and increased NK2001- or NK2002-suppressed hippocampal BDNF expression. However, NK2003-induced cognitive impairment-like behavior and hippocampal Iba1[+] cell population and TNF-α expression were partially, but not significantly, attenuated by celiac vagotomy. Furthermore, celiac vagotomy did not affect NK2001-, NK2002-, or NK2003-induced lipopolysaccharide (LPS) levels in the blood and feces and TNF-α expression and NF-κB-positive cell population in the colon. In conclusion, LPS-producing NK2001 and NK2002 and LPS-nonproducing NK2003 may induce NF-κB-mediated neuroinflammation through the translocation of byproducts such as LPS and peptidoglycan into the brain through gut-blood/vagus nerve-brain and gut-blood-brain pathways, respectively, resulting in cognitive impairment.}, }
@article {pmid38428570, year = {2024}, author = {Ran, X and Hu, G and Guo, W and Li, K and Wang, X and Liu, J and Fu, S}, title = {Hesperetin regulates the intestinal flora and inhibits the TLR4/NF-κB signaling axis to protect the blood-milk barrier and prevent mastitis.}, journal = {Life sciences}, volume = {342}, number = {}, pages = {122533}, doi = {10.1016/j.lfs.2024.122533}, pmid = {38428570}, issn = {1879-0631}, mesh = {Humans ; Female ; Animals ; Mice ; NF-kappa B/metabolism ; Toll-Like Receptor 4/metabolism ; Milk/metabolism ; Lactation ; Lipopolysaccharides/adverse effects ; *Gastrointestinal Microbiome ; *Mastitis/prevention &amp; control/metabolism/pathology ; Mammary Glands, Animal/metabolism ; *Hesperidin ; }, abstract = {The World Health Organization recommends breastfeeding for 6 months, but mastitis, a common disease during lactation, presents a major obstacle to fulfilling this recommendation. Maternal nutrient intake during lactation has been shown to be related to mastitis. Therefore, this study aimed to explore the effect of hesperetin, a phytonutrient, on mastitis. The oral administration of hesperetin to lipopolysaccharide (LPS)-induced mastitis mice alleviated their pathological damage, reduced the secretion of pro-inflammatory cytokines, and maintained the integrity of their blood-milk barrier. Moreover, our results showed that oral administration of hesperetin regulates the composition of the intestinal flora of mice. Fecal microbial transplantation (FMT) from the mice of hesperetin group alleviated LPS-induced mastitis in recipient mice. In additional, hesperetin attenuated the inflammatory response and increased the expression of tight junction proteins (TJs) in LPS-stimulated mouse mammary epithelial cells (mMECs). Through network pharmacological analysis and further research, we demonstrated hesperetin inhibits the expression of TLR4 and the activation of NF-κB signaling. In conclusion, hesperetin protects the blood-milk barrier and improve mastitis by regulating intestinal flora and inhibiting the activation of TLR4/NF-κB signaling axis. This study provides a theoretical basis for lactating females to consume hesperetin as a supplement to prevent mastitis and maintain mammary health.}, }
@article {pmid38427251, year = {2024}, author = {Niccolai, E and Martinelli, I and Quaranta, G and Nannini, G and Zucchi, E and De Maio, F and Gianferrari, G and Bibbò, S and Cammarota, G and Mandrioli, J and Masucci, L and Amedei, A}, title = {Fecal Microbiota Transplantation in Amyotrophic Lateral Sclerosis: Clinical Protocol and Evaluation of Microbiota Immunity Axis.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2761}, number = {}, pages = {373-396}, pmid = {38427251}, issn = {1940-6029}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Amyotrophic Lateral Sclerosis/therapy ; *Microbiota ; *Gastrointestinal Microbiome/physiology ; Clinical Protocols ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; }, abstract = {The fecal microbial transplantation (FMT) is a therapeutic transplant of fecal microbiota from healthy donors to patients. This practice is aimed at restoring eubiosis and rebalancing the enteric and systemic immune responses, and then eliminating pathogenic triggers of multiple disease, including neurodegenerative diseases. Alterations of gut microbiota (GM) affect the central nervous system (CNS) health, impacting neuro-immune interactions, synaptic plasticity, myelination, and skeletal muscle function. T-regulatory lymphocytes (Treg) are among the most important players in the pathogenesis of amyotrophic lateral sclerosis (ALS), altering the disease course. Along with circulating neuropeptides, other immune cells, and the gut-brain axis, the GM influences immunological tolerance and controls Treg's number and suppressive functions. A double-blind, controlled, multicenter study on FMT in ALS patients has been designed to evaluate if FMT can modulate neuroinflammation, by restoring Treg number, thus modifying disease activity and progression.}, }
@article {pmid38423412, year = {2024}, author = {Luo, Y and Fu, S and Liu, Y and Kong, S and Liao, Q and Lin, L and Li, H}, title = {Banxia Xiexin decoction modulates gut microbiota and gut microbiota metabolism to alleviate DSS-induced ulcerative colitis.}, journal = {Journal of ethnopharmacology}, volume = {326}, number = {}, pages = {117990}, doi = {10.1016/j.jep.2024.117990}, pmid = {38423412}, issn = {1872-7573}, mesh = {Male ; Animals ; Mice ; Mice, Inbred C57BL ; *Colitis, Ulcerative/chemically induced/drug therapy ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Tumor Necrosis Factor-alpha ; Amino Acids ; *Antifibrinolytic Agents ; Purines ; Body Weight ; Lipids ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Colon ; *Colitis ; *Drugs, Chinese Herbal ; }, abstract = {Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine prescription for treating ulcerative colitis (UC). However, its potential mechanism of action is still unclear.<br><br>AIM OF THE STUDY: Reveal the correlation between the beneficial impacts of BXD on UC and the composition of the gut microbiota.<br><br>MATERIALS AND METHODS: The major constituents of BXD were identified using the HPLC-DAD technique. An experimental model of UC was induced in male C57BL/6 mice by administering dextran sodium sulfate (DSS). A total of 48 mice were divided into different groups, including control, model, high-dose BXD treatment, medium-dose BXD treatment, low-dose BXD treatment, and a group treated with 5-amino acid salicylic acid (5-ASA). Body weight changes and disease activity index (DAI) scores were documented; colon length, colon index, spleen index, and thymus index scores were determined; myeloperoxidase (MPO) and tumor necrosis factor-&#x3b1; (TNF-&#x3b1;) activities were assessed; and histological staining with hematoxylin-eosin and alcian blue/phosphate Schiff was performed. The immunofluorescence technique was employed to examine the presence of ZO-1 and occludin in the colon tissue. 16S rRNA sequencing was employed to assess the gut microbiota's diversity and metabolomics was utilized to examine alterations in metabolites within the gut microbiota. The impact of BXD on the gut microbiota was confirmed through fecal microbiota transplantation (FMT).<br><br>RESULTS: BXD exhibited a positive impact on UC mice, particularly in the high-dose BXD treatment group. The BXD group experienced weight recovery, decreased DAI scores, improved colon length, and restored of spleen and thymus index scores compared to the DSS group. Additionally, BXD alleviated colon damage and the inflammatory response while restoring intestinal barrier function. FMT in BXD-treated mice also showed therapeutic effects in UC mice. At the phylum level, the relative abundance of Desulfobacterota, Deferribacterota and Actinobacteriota increased; at the genus level, g__norank__f__Muribaculaceae, Dubosiella, Akkermansia, and Lactobacillus increased, whereas Faecalibaculum, Alloprevotella, Turicibacter, and g_Paraprevotella decreased. g__norank_f__Muribaculaceae was positively correlated with body weight and colon length and negatively with colon index scores, splenic index scores, and MPO levels; Alloprevotella was positively correlated with splenic index scores, histological scores, and TNF-&#x3b1; levels and negatively with thymus index scores and thymus index scores. Faecalibaculum was positively correlated with colon index scores and MPO levels. Metabolic investigations revealed 58 potential indicators, primarily associated with the metabolism of amino acids, purines, and lipids. Alloprevotella, g_Paraprevotella, and Bifidobacterium were strongly associated with metabolic pathways.<br><br>CONCLUSION: BXD showed beneficial therapeutic effects in UC mice. The mechanism may be by promoting the balance and variety of gut microbiota, as well as regulating the metabolism of amino acids, purines, and lipids.}, }
@article {pmid38419010, year = {2024}, author = {Nooij, S and Vendrik, KEW and Zwittink, RD and Ducarmon, QR and Keller, JJ and Kuijper, EJ and Terveer, EM and , }, title = {Long-term beneficial effect of faecal microbiota transplantation on colonisation of multidrug-resistant bacteria and resistome abundance in patients with recurrent Clostridioides difficile infection.}, journal = {Genome medicine}, volume = {16}, number = {1}, pages = {37}, pmid = {38419010}, issn = {1756-994X}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Clostridioides difficile/genetics ; Feces/microbiology ; *Microbiota ; *Clostridium Infections/therapy/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases.<br><br>METHODS: We study the effect of FMT in patients with multiple recurrent C. difficile infections on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3&#xa0;weeks) and long term (1-3&#xa0;years), combining culture methods and faecal metagenomics.<br><br>RESULTS: Based on MDR culture (n&#x2009;=&#x2009;87 patients), we notice a decrease of 11.5% in the colonisation rate of MDR bacteria after FMT (20/87 before FMT&#x2009;=&#x2009;23%, 10/87 3&#xa0;weeks after FMT). Metagenomic sequencing of patient stool samples (n&#x2009;=&#x2009;63) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to stools of their corresponding healthy donors (n&#x2009;=&#x2009;11). Furthermore, plasmid predictions in metagenomic data indicate that patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long term (n&#x2009;=&#x2009;22 patients), the recipients' resistomes are still donor-like, suggesting the effect of FMT may last for years.<br><br>CONCLUSIONS: Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes.}, }
@article {pmid38417315, year = {2024}, author = {Chen, X and Zhu, D and Ge, R and Bao, Z}, title = {Fecal transplantation of young mouse donors effectively improves enterotoxicity in elderly recipients exposed to triphenyltin.}, journal = {Ecotoxicology and environmental safety}, volume = {273}, number = {}, pages = {116140}, doi = {10.1016/j.ecoenv.2024.116140}, pmid = {38417315}, issn = {1090-2414}, mesh = {Humans ; Mice ; Animals ; Aged ; Infant ; *Fecal Microbiota Transplantation ; *Organotin Compounds/toxicity ; Feces ; RNA, Messenger/metabolism ; }, abstract = {Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1β, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.}, }
@article {pmid38417203, year = {2024}, author = {Zhu, X and Zhao, L and Lei, L and Zhu, Y and Xu, J and Liu, L}, title = {Fecal microbiota transplantation ameliorates abdominal obesity through inhibiting microbiota-mediated intestinal barrier damage and inflammation in mice.}, journal = {Microbiological research}, volume = {282}, number = {}, pages = {127654}, doi = {10.1016/j.micres.2024.127654}, pmid = {38417203}, issn = {1618-0623}, mesh = {Mice ; Humans ; Animals ; *Fecal Microbiota Transplantation ; Obesity, Abdominal ; Dysbiosis/therapy ; Obesity/drug therapy/metabolism ; Inflammation ; *Microbiota ; Mice, Inbred C57BL ; }, abstract = {Abdominal obesity (AO), characterized by the excessive abdominal fat accumulation, has emerged as a significant public health concern due to its metabolic complications and escalating prevalence worldwide, posing a more pronounced threat to human health than general obesity. While certain studies have indicated that intestinal flora contributed to diet-induced general obesity, the precise involvement of gut microbiota in the development of AO, specifically the accumulation of abdominal fat, remains inadequately explored. In this study, the 16 S rDNA sequencing was employed to analyze gut flora alterations, and the intestinal microbiota dysbiosis characterized by a vanishing decline of Akkermansia was found in the AO group. Along with notable gut microbiota changes, the intestinal mucosal barrier damage and metabolic inflammation were detected, which collectively promoted metabolic dysregulation in AO. Furthermore, the metabolic inflammation and AO were ameliorated after the intestinal microbiota depletion with antibiotics (ABX) drinking, underscoring a significant involvement of gut microbiota dysbiosis in the progression of AO. More importantly, our findings demonstrated that the transplantation of healthy intestinal flora successfully reversed the gut microbiota dysbiosis, particularly the decline of Akkermansia in the AO group. The gut flora reshaping has led to the repair of gut barrier damage and mitigation of metabolic inflammation, which ultimately ameliorated abdominal fat deposition. Our study established the role of interactions between gut flora, mucus barrier, and metabolic inflammation in the development of AO, thereby offering a theoretical foundation for the clinical application of fecal microbiota transplantation (FMT) as a treatment for AO.}, }
@article {pmid38414441, year = {2024}, author = {Wang, N and Huo, Y and Gao, X and Li, Y and Cheng, F and Zhang, Z}, title = {Lead exposure exacerbates liver injury in high-fat diet-fed mice by disrupting the gut microbiota and related metabolites.}, journal = {Food &amp; function}, volume = {15}, number = {6}, pages = {3060-3075}, doi = {10.1039/d3fo05148j}, pmid = {38414441}, issn = {2042-650X}, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome ; Lead/toxicity ; Diet, High-Fat/adverse effects ; Dysbiosis ; Inflammation ; Anti-Bacterial Agents ; Lipopolysaccharides ; Liver ; }, abstract = {Lead (Pb) is a widespread toxic endocrine disruptor that could cause liver damage and gut microbiota dysbiosis. However, the causal relationship and underlying mechanisms between the gut microbiota and Pb-induced liver injury are unclear. In this study, we investigated the metabolic toxicity caused by Pb exposure in normal chow (Chow) and high-fat diet (HFD) mice and confirmed the causal relationship by fecal microbial transplantation (FMT) and antibiotic cocktail experiments. The results showed that Pb exposure exacerbated HFD-induced hepatic lipid deposition, fibrosis, and inflammation, but it had no significant effect on Chow mice. Pb increased serum lipopolysaccharide (LPS) levels and induced intestinal inflammation and barrier damage by activating TLR4/NFκB/MLCK in HFD mice. Furthermore, Pb exposure disrupted the gut microbiota, reduced short-chain fatty acid (SCFA) concentrations and the colonic SCFA receptors, G protein-coupled receptor (GPR) 41/43/109A, in HFD mice. Additionally, Pb significantly inhibited the hepatic GPR109A-mediated adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway, resulting in hepatic lipid accumulation. FMT from Pb-exposed HFD mice exacerbated liver damage, disturbed lipid metabolic pathways, impaired intestinal barriers, and altered the gut microbiota and metabolites in recipient mice. However, mice exposed to HFD + Pb and HFD mice had similar levels of these biomarkers in microbiota depleted by antibiotics. In conclusion, our study provides new insights into gut microbiota dysbiosis as a potential novel mechanism for human health related to liver function impairment caused by Pb exposure.}, }
@article {pmid38414430, year = {2024}, author = {Moinul, D and Hao, C and Dimitropoulos, G and Taylor, VH}, title = {Patient Perceptions of Microbiome-Based Therapies as Novel Treatments for Mood Disorders: A Mixed Methods Study: Perceptions des patients sur les thérapies basées sur le microbiome pour les troubles de l'humeur : une étude à méthodes mixtes.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {69}, number = {7}, pages = {503-512}, pmid = {38414430}, issn = {1497-0015}, mesh = {Humans ; Female ; Male ; Adult ; Middle Aged ; *Bipolar Disorder/therapy ; *Depressive Disorder, Major/therapy ; *Fecal Microbiota Transplantation ; *Probiotics/pharmacology/therapeutic use ; Prebiotics ; Gastrointestinal Microbiome/physiology ; }, abstract = {OBJECTIVE: Medications are critical for treating major depressive disorder (MDD) and bipolar disorder (BD). Unfortunately, 30% to 40% of individuals do not respond well to current pharmacotherapy. Given the compelling growing body of research on the gut-brain axis, this study aims to assess patient perspectives regarding microbiome-based therapies (MBT) such as probiotics, prebiotics, dietary changes, or fecal microbiota transplantation (FMT) in the management of MDD and BD.<br><br>METHODS: This single-centred observational study used quantitative and qualitative assessments to examine patient perceptions of MBT. Participants diagnosed with MDD or BD completed an anonymous questionnaire obtaining demographics, prior medication history, and symptom burden. Self-assessment questionnaires specific to each diagnosis were also used: Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), Altman Self-Rating Mania Scale (ASRM), and General Anxiety Disorder Questionnaire (GAD-7). A logistic regression model analysed the association of MBT acceptance with disorder type, QIDS-SR, and GAD-7 scores. A bootstrap method assessed the proportion of MBT acceptance. The qualitative assessment consisted of 30-minute interviews to elicit perceptions and attitudes towards MBT.<br><br>RESULTS: The qualitative assessment achieved information power with n&#x2009;=&#x2009;20. Results from the 63-item MBT questionnaire (n&#x2009;=&#x2009;43) showed probiotics (37.2%) as the top choice, followed by FMT (32.6%), dietary change (25.6%), and prebiotics (4.6%). A majority of participants (72.1%) expressed willingness to try MBT for their mood disorder, however, logistic regression analysis did not identify statistically significant predictors for MBT acceptance among disorder type, QIDS-SR, and GAD-7.<br><br>CONCLUSION: There is an increased focus on the gut microbiota's role in mood disorders' etiology and treatment. Promising research and patient interest underscore the necessity for exploring and educating on patient perspectives and the factors influencing attitudes towards MBT.}, }
@article {pmid38414054, year = {2024}, author = {Ma, YY and Li, X and Yu, JT and Wang, YJ}, title = {Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {12}, pmid = {38414054}, issn = {2047-9158}, support = {92249305//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; *Amyotrophic Lateral Sclerosis ; *Alzheimer Disease ; *Parkinson Disease/therapy ; }, abstract = {The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), are complex and multifaceted. A growing body of evidence suggests that the gut microbiome plays crucial roles in the development and progression of neurodegenerative diseases. Clinicians have come to realize that therapeutics targeting the gut microbiome have the potential to halt the progression of neurodegenerative diseases. This narrative review examines the alterations in the gut microbiome in AD, PD, ALS and HD, highlighting the close relationship between the gut microbiome and the brain in neurodegenerative diseases. Processes that mediate the gut microbiome-brain communication in neurodegenerative diseases, including the immunological, vagus nerve and circulatory pathways, are evaluated. Furthermore, we summarize potential therapeutics for neurodegenerative diseases that modify the gut microbiome and its metabolites, including diets, probiotics and prebiotics, microbial metabolites, antibacterials and faecal microbiome transplantation. Finally, current challenges and future directions are discussed.}, }
@article {pmid38413211, year = {2024}, author = {Yau, YK and Su, Q and Xu, Z and Tang, W and Ching, JYL and Cheung, CP and Fung, M and Ip, M and Chan, PKS and Chan, FKL and Ng, SC}, title = {Faecal microbiota transplantation for patients with irritable bowel syndrome: abridged secondary publication.}, journal = {Hong Kong medical journal = Xianggang yi xue za zhi}, volume = {30 Suppl 1}, number = {1}, pages = {34-38}, pmid = {38413211}, issn = {1024-2708}, }
@article {pmid38412097, year = {2024}, author = {Dong, J and Wang, B and Xiao, Y and Liu, J and Wang, Q and Xiao, H and Jin, Y and Liu, Z and Chen, Z and Li, Y and Fan, S and Li, Y and Cui, M}, title = {Roseburia intestinalis sensitizes colorectal cancer to radiotherapy through the butyrate/OR51E1/RALB axis.}, journal = {Cell reports}, volume = {43}, number = {3}, pages = {113846}, doi = {10.1016/j.celrep.2024.113846}, pmid = {38412097}, issn = {2211-1247}, mesh = {Humans ; Animals ; Mice ; Butyrates/pharmacology ; Clostridiales ; Azoxymethane/toxicity ; *Colorectal Neoplasms/metabolism ; *Rectal Neoplasms ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Mice, Inbred C57BL ; Receptors, G-Protein-Coupled ; }, abstract = {The radioresistant signature of colorectal cancer (CRC) hampers the clinical utility of radiotherapy. Here, we find that fecal microbiota transplantation (FMT) potentiates the tumoricidal effects of radiation and degrades the intertwined adverse events in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. FMT cumulates Roseburia intestinalis (R. intestinalis) in the gastrointestinal tract. Oral gavage of R. intestinalis assembles at the CRC site and synthetizes butyrate, sensitizing CRC to radiation and alleviating intestinal toxicity in primary and CRC hepatic metastasis mouse models. R. intestinalis-derived butyrate activates OR51E1, a G-protein-coupled receptor overexpressing in patients with rectal cancer, facilitating radiogenic autophagy in CRC cells. OR51E1 shows a positive correlation with RALB in clinical rectal cancer tissues and CRC mouse model. Blockage of OR51E1/RALB signaling restrains butyrate-elicited autophagy in irradiated CRC cells. Our findings highlight that the gut commensal bacteria R. intestinalis motivates radiation-induced autophagy to accelerate CRC cell death through the butyrate/OR51E1/RALB axis and provide a promising radiosensitizer for CRC in a pre-clinical setting.}, }
@article {pmid38412095, year = {2024}, author = {Hu, J and He, K and Yang, Y and Huang, C and Dou, Y and Wang, H and Zhang, G and Wang, J and Niu, C and Bi, G and Zhang, L and Zhu, S}, title = {Amino acid formula induces microbiota dysbiosis and depressive-like behavior in mice.}, journal = {Cell reports}, volume = {43}, number = {3}, pages = {113817}, doi = {10.1016/j.celrep.2024.113817}, pmid = {38412095}, issn = {2211-1247}, mesh = {Humans ; Infant ; Female ; Cattle ; Child ; Animals ; Mice ; Infant Formula/chemistry ; Amino Acids ; Dysbiosis ; *Milk Hypersensitivity ; *Microbiota ; }, abstract = {Amino acid formula (AAF) is increasingly consumed in infants with cow's milk protein allergy; however, the long-term influences on health are less described. In this study, we established a mouse model by subjecting neonatal mice to an amino acid diet (AAD) to mimic the feeding regimen of infants on AAF. Surprisingly, AAD-fed mice exhibited dysbiotic microbiota and increased neuronal activity in both the intestine and brain, as well as gastrointestinal peristalsis disorders and depressive-like behavior. Furthermore, fecal microbiota transplantation from AAD-fed mice or AAF-fed infants to recipient mice led to elevated neuronal activations and exacerbated depressive-like behaviors compared to that from normal chow-fed mice or cow's-milk-formula-fed infants, respectively. Our findings highlight the necessity to avoid the excessive use of AAF, which may influence the neuronal development and mental health of children.}, }
@article {pmid38411876, year = {2024}, author = {Mascaretti, F and Haider, S and Amoroso, C and Caprioli, F and Ramai, D and Ghidini, M}, title = {Role of the Microbiome in the Diagnosis and Management of Gastroesophageal Cancers.}, journal = {Journal of gastrointestinal cancer}, volume = {55}, number = {2}, pages = {662-678}, pmid = {38411876}, issn = {1941-6636}, mesh = {Humans ; *Esophageal Neoplasms/microbiology/therapy/diagnosis/pathology ; *Stomach Neoplasms/microbiology/therapy/diagnosis/pathology ; *Gastrointestinal Microbiome ; *Dysbiosis/diagnosis/microbiology/therapy ; Probiotics/therapeutic use/administration &amp; dosage ; Adenocarcinoma/microbiology/therapy/diagnosis/pathology ; }, abstract = {PURPOSE: Stomach and esophageal cancers are among the highest mortality from cancers worldwide. Microbiota has an interplaying role within the human gastrointestinal (GI) tract. Dysbiosis occurs when a disruption of the balance between the microbiota and the host happens. With this narrative review, we discuss the main alterations in the microbiome of gastroesophageal cancer, revealing its potential role in the pathogenesis, early detection, and treatment.<br><br>RESULTS: Helicobacter pylori plays a major role the development of a cascade of preneoplastic conditions ranging from atrophic gastritis to metaplasia and dysplasia, ultimately culminating in gastric cancer, while other pathogenic agents are Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli, and Lactobacillus. Campylobacter species (spp.)'s role in the progression of esophageal adenocarcinoma may parallel that of Helicobacter pylori in the context of gastric cancer, with other esophageal carcinogenic agents being Escherichia coli, Bacteroides fragilis, and Fusobacterium nucleatum. Moreover, gut microbiome could significantly alter the outcomes of chemotherapy and immunotherapy. The gut microbiome can be modulated through interventions such as antibiotics, probiotics, or prebiotics intake. Fecal microbiota transplantation has emerged as a therapeutic strategy as well.<br><br>CONCLUSIONS: Nowadays, it is widely accepted that changes in the normal gut microbiome causing dysbiosis and immune dysregulation play a role gastroesophageal cancer. Different interventions, including probiotics and prebiotics intake are being developed to improve therapeutic outcomes and mitigate toxicities associated with anticancer treatment. Further studies are required in order to introduce the microbiome among the available tools of precision medicine in the field of anticancer treatment.}, }
@article {pmid38411457, year = {2024}, author = {Vieujean, S and Gillard, R and Delanaye, P and Seidel, L and Bequet, E and Salée, C and Meuwis, MA and Massot, C and Pierre, N and Meunier, P and Cavalier, E and Louis, E}, title = {Matrix gla protein, a potential marker of tissue remodelling and physiological ageing of the gut in crohn's disease.}, journal = {Scandinavian journal of gastroenterology}, volume = {59}, number = {3}, pages = {296-303}, doi = {10.1080/00365521.2023.2286913}, pmid = {38411457}, issn = {1502-7708}, mesh = {Female ; Humans ; *Crohn Disease ; Matrix Gla Protein ; Constriction, Pathologic ; Aging ; Leukocyte L1 Antigen Complex ; }, abstract = {BACKGROUND: The inactive dephosphorylated and uncarboxylated form of the matrix Gla protein (dp-ucMGP) has been shown to be increased in plasma of inflammatory bowel disease (IBD) patients. Our aim was to assess if the plasmatic level of dp-ucMGP could reflect disease endoscopic activity, presence of strictures and cumulative structural bowel damage in Crohn's disease (CD) patients.<br><br>METHODS: The plasmatic level of dp-ucMGP was measured in a monocentric cohort of prospectively recruited patients. The analysis was done by chemiluminescent immunoassay on blood samples collected the day of a planned ileocolonoscopy. In addition to classical clinical data (gender, age, body mass index (BMI), disease duration, current treatment), endoscopic data (disease location, Crohn's Disease Endoscopic Index of Severity (CDEIS), mucosal healing (MH), presence of 9&#x2009;CD lesion types) and biological markers (faecal calprotectin and C-reactive protein (CRP)) were collected. The association between dp-ucMGP level and L&#xe9;mann index was also investigated. Univariate linear regression was used to investigate the relationship between dp-ucMGP level and different parameters collected.<br><br>RESULTS: A total of 82 ileocolonoscopies and dp-ucMGP assays were performed in 75&#x2009;CD patients (45 females; 37 ileocolonic, 19 ileal and 19 colonic diseases) between October 2012 and November 2019. A total of 24 patients (29.3%) showed MH. The dp-ucMGP levels were not associated with MH, CDEIS, faecal calprotectin or CRP levels. Plasmatic dp-ucMGP levels increased significantly with age (p&#x2009;=&#x2009;0.0032), disease duration (p&#x2009;=&#x2009;0.0033), corticosteroids use (p&#x2009;=&#x2009;0.019) and tended to increase in patients with intestinal strictures (p&#x2009;=&#x2009;0.086) but not with the L&#xe9;mann index.<br><br>CONCLUSION: The significant increase of plasmatic dp-ucMGP levels with age, disease duration and the trend observed in patients with non-ulcerated strictures may suggest that this extracellular matrix protein could be a marker of tissue remodelling and physiological ageing of the gut.}, }
@article {pmid38410824, year = {2023}, author = {Pasam, T and Dandekar, MP}, title = {Fecal microbiota transplantation unveils sex-specific differences in a controlled cortical impact injury mouse model.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1336537}, pmid = {38410824}, issn = {1664-302X}, abstract = {INTRODUCTION: Contusion type of traumatic brain injury (TBI) is a major cause of locomotor disability and mortality worldwide. While post-TBI deleterious consequences are influenced by gender and gut dysbiosis, the sex-specific importance of commensal gut microbiota is underexplored after TBI. In this study, we investigated the impact of controlled cortical impact (CCI) injury on gut microbiota signature in a sex-specific manner in mice.<br><br>METHODS: We depleted the gut microflora of male and female C57BL/6 mice using antibiotic treatment. Thereafter, male mice were colonized by the gut microbiota of female mice and vice versa, employing the fecal microbiota transplantation (FMT) method. CCI surgery was executed using a stereotaxic impactor (Impact One&#x2122;). For the 16S rRNA gene amplicon study, fecal boli of mice were collected at 3 days post-CCI (dpi).<br><br>RESULTS AND DISCUSSION: CCI-operated male and female mice exhibited a significant alteration in the genera of Akkermansia, Alistipes, Bacteroides, Clostridium, Lactobacillus, Prevotella, and Ruminococcus. At the species level, less abundance of Lactobacillus helveticus and Lactobacillus hamsteri was observed in female mice, implicating the importance of sex-specific bacteriotherapy in CCI-induced neurological deficits. FMT from female donor mice to male mice displayed an increase in genera of Alistipes, Lactobacillus, and Ruminococcus and species of Bacteroides acidifaciens and Ruminococcus gnavus. Female FMT-recipient mice from male donors showed an upsurge in the genus Lactobacillus and species of Lactobacillus helveticus, Lactobacillus hamsteri, and Prevotella copri. These results suggest that the post-CCI neurological complications may be influenced by the differential gut microbiota perturbation in male and female mice.}, }
@article {pmid38410679, year = {2024}, author = {Chen, S and Li, M and Tong, C and Wang, Y and He, J and Shao, Q and Liu, Y and Wu, Y and Song, Y}, title = {Regulation of miRNA expression in the prefrontal cortex by fecal microbiota transplantation in anxiety-like mice.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1323801}, pmid = {38410679}, issn = {1664-0640}, abstract = {BACKGROUND: The gut-brain axis and gut microbiota have emerged as key players in emotional disorders. Recent studies suggest that alterations in gut microbiota may impact psychiatric symptoms through brain miRNA along the gut-brain axis. However, direct evidence linking gut microbiota to the pathophysiology of generalized anxiety disorder (GAD) via brain miRNA is limited. In this study, we explored the effects of fecal microbiota transplantation (FMT) from GAD donors on gut microbiota and prefrontal cortex miRNA in recipient mice, aiming to understand the relationship between these two factors.<br><br>METHODS: Anxiety scores and gut microbiota composition were assessed in GAD patients, and their fecal samples were utilized for FMT in C57BL/6J mice. Anxiety-like behavior in mice was evaluated using open field and elevated plus maze tests. High-throughput sequencing of gut microbiota 16S rRNA and prefrontal cortex miRNA was performed.<br><br>RESULTS: The fecal microbiota of GAD patients exhibited a distinct microbial structure compared to the healthy group, characterized by a significant decrease in Verrucomicrobia and Akkermansia, and a significant increase in Actinobacteria and Bacteroides. Subsequent FMT from GAD patients to mice induced anxiety-like behavior in recipients. Detailed analysis of gut microbiota composition revealed lower abundances of Verrucomicrobia, Akkermansia, Bifidobacterium, and Butyricimonas, and higher abundances of Deferribacteres, Allobaculum, Bacteroides, and Clostridium in mice that received FMT from GAD patients. MiRNA analysis identified five key miRNAs affecting GAD pathogenesis, including mmu-miR-10a-5p, mmu-miR-1224-5p, mmu-miR-218-5p, mmu-miR-10b-5p, and mmu-miR-488-3p. Notably, mmu-miR-488-3p showed a strong negative correlation with Verrucomicrobia and Akkermansia.<br><br>CONCLUSION: This study demonstrates that anxiety-like behavior induced by human FMT can be transmitted through gut microbiota and is associated with miRNA expression in the prefrontal cortex. It is inferred that the reduction of Akkermansia caused by FMT from GAD patients leads to the upregulation of mmu-miR-488-3p expression, resulting in the downregulation of its downstream target gene Creb1 and interference with its related signaling pathway. These findings highlight the gut microbiota's crucial role in the GAD pathophysiology.}, }
@article {pmid38409485, year = {2024}, author = {Yadav, A and Yadav, R and Sharma, V and Dutta, U}, title = {A comprehensive guide to assess gut mycobiome and its role in pathogenesis and treatment of inflammatory bowel disease.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {43}, number = {1}, pages = {112-128}, pmid = {38409485}, issn = {0975-0711}, mesh = {Humans ; *Mycobiome/physiology ; Dysbiosis/therapy/microbiology ; Ecosystem ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Gastrointestinal Microbiome ; }, abstract = {Inflammatory bowel disease (IBD) is an immune mediated chronic inflammatory disorder of gastrointestinal tract, which has underlying multifactorial pathogenic determinants such as environmental factors, susceptibility genes, gut microbial dysbiosis and a dysregulated immune response. Human gut is a frequent inhabitant of complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi and other microorganisms that have an undisputable role in maintaining balanced homeostasis. All of these microbes interact with immune system and affect human gut physiology either directly or indirectly with interaction of each other. Intestinal fungi represent a smaller but crucial component of the human gut microbiome. Besides interaction with bacteriome and virome, it helps in balancing homoeostasis between pathophysiological and physiological processes, which is often dysregulated in patients with IBD. Understanding of gut mycobiome and its clinical implications are still in in its infancy as opposed to bacterial component of gut microbiome, which is more often focused. Modulation of gut mycobiome represents a novel and promising strategy in the management of patients with IBD. Emerging mycobiome-based therapies such as diet interventions, fecal microbiota transplantation (FMT), probiotics (both fungal and bacterial strains) and antifungals exhibit substantial effects in calibrating the gut mycobiome and restoring dysbalanced immune homeostasis by restoring the core gut mycobiome. In this review, we summarized compositional and functional diversity of the gut mycobiome in healthy individuals and patients with IBD, gut mycobiome dysbiosis in patients with IBD, host immune-fungal interactions and therapeutic role of modulation of intestinal fungi in patients with IBD.}, }
@article {pmid38409241, year = {2024}, author = {Kasahara, N and Teratani, T and Yokota, S and Sakuma, Y and Sasanuma, H and Fujimoto, Y and Ijichi, T and Urahashi, T and Yoshitomi, H and Kitayama, J and Sata, N}, title = {Dietary polyamines promote intestinal adaptation in an experimental model of short bowel syndrome.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4605}, pmid = {38409241}, issn = {2045-2322}, support = {JP26461926//JSPS KAKENHI/ ; }, mesh = {Rats ; Animals ; Male ; *Short Bowel Syndrome/metabolism ; Polyamines/metabolism ; Rats, Sprague-Dawley ; Rats, Inbred Lew ; Intestine, Small/metabolism ; Diet ; Models, Theoretical ; Intestinal Mucosa/metabolism ; }, abstract = {Intestinal adaptation does not necessarily recover absorptive capacity in short bowel syndrome (SBS), sometimes resulting in intestinal failure-associated liver disease (IFALD). Additionally, its therapeutic options remain limited. Polyamines (spermidine and spermine) are known as one of the autophagy inducers and play important roles in promoting the weaning process; however, their impact on intestinal adaptation is unknown. The aim of this study was to investigate the impact of polyamines ingestion on adaptation and hepatic lipid metabolism in SBS. We performed resection of two-thirds of the small intestine in male Lewis rats as an SBS model. They were allocated into three groups and fed different polyamine content diets (0%, 0.01%, 0.1%) for 30 days. Polyamines were confirmed to distribute to remnant intestine, whole blood, and liver. Villous height and number of Ki-67-positive cells in the crypt area increased with the high polyamine diet. Polyamines increased secretory IgA and mucin content in feces, and enhanced tissue Claudin-3 expression. In contrast, polyamines augmented albumin synthesis, mitochondrial DNA copy number, and ATP storage in the liver. Moreover, polyamines promoted autophagy flux and activated AMP-activated protein kinase with suppression of lipogenic gene expression. Polyamines ingestion may provide a new therapeutic option for SBS with IFALD.}, }
@article {pmid38408636, year = {2024}, author = {Yousef, M and Rob, M and Varghese, S and Rao, S and Zamir, F and Paul, P and Chaari, A}, title = {The effect of microbiome therapy on COVID-19-induced gut dysbiosis: A narrative and systematic review.}, journal = {Life sciences}, volume = {342}, number = {}, pages = {122535}, doi = {10.1016/j.lfs.2024.122535}, pmid = {38408636}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/complications/therapy ; *Dysbiosis/etiology/therapy ; Microbiota ; *Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {AIMS: Emerging evidence highlights the role of COVID-19 in instigating gut dysbiosis, with repercussions on disease severity and bidirectional gut-organ communication involving the lung, heart, brain, and liver. This study aims to evaluate the efficacy of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) in addressing gut dysbiosis associated with COVID-19, as well as their impact on related disease severity and clinical outcomes.<br><br>MATERIALS AND METHODS: We systematically review 27 studies exploring the efficacy of different microbiome-modulating therapies: probiotics, prebiotics, synbiotics, and fecal microbiota transplantation as potential interventions for COVID-19.<br><br>KEY FINDINGS: The probiotics and synbiotics investigated encompassed a spectrum of eight bacterial and fungal genera, namely Lactobacillus, Bifidobacterium, Streptococcus, Enterococcus, Pediococcus, Bacillus, Saccharomyces, and Kluyveromyces. Noteworthy prebiotics employed in these studies included chestnut tannin, galactooligosaccharides, fructooligosaccharides, xylooligosaccharide, and resistant dextrin. The majority of the investigated biotics exhibited positive effects on COVID-19 patients, manifesting in symptom alleviation, inflammation reduction, and notable decreases in mortality rates. Five studies reported death rates, showing an average mortality ranging from 0&#xa0;% to 11&#xa0;% in the intervention groups, as compared to 3&#xa0;% to 30&#xa0;% in the control groups. Specifically, probiotics, prebiotics, and synbiotics demonstrated efficacy in diminishing the duration and severity of symptoms while significantly accelerating viral and symptomatic remission. FMT emerged as a particularly effective strategy, successfully restoring gut microbiota and ameliorating gastrointestinal disorders.<br><br>SIGNIFICANCE: The insights gleaned from this review significantly contribute to our broader comprehension of the therapeutic potential of biotics in addressing COVID-19-related gut dysbiosis and mitigating secondary multi-organ complications.}, }
@article {pmid38407390, year = {2024}, author = {Tian, B and Pan, Y and Zhou, X and Jiang, Y and Zhang, X and Luo, X and Yang, K}, title = {Yellow leaf green tea modulates the AMPK/ACC/SREBP1c signaling pathway and gut microbiota in high-fat diet-induced mice to alleviate obesity.}, journal = {Journal of the science of food and agriculture}, volume = {104}, number = {10}, pages = {5882-5895}, doi = {10.1002/jsfa.13413}, pmid = {38407390}, issn = {1097-0010}, support = {2022C04036//Zhejiang Provincial Key Research and Development Program/ ; 2023C02040//Zhejiang Provincial Key Research and Development Program/ ; }, mesh = {Animals ; Humans ; Male ; Mice ; Acetyl-CoA Carboxylase/metabolism ; AMP-Activated Protein Kinases/metabolism ; Anti-Obesity Agents/pharmacology/administration &amp; dosage ; Bacteria/classification/drug effects ; *Camellia sinensis/chemistry ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Liver/metabolism/drug effects ; Mice, Inbred C57BL ; *Obesity/diet therapy/drug therapy/microbiology ; *Plant Extracts/pharmacology/chemistry ; *Plant Leaves/chemistry ; *Signal Transduction/drug effects ; Sterol Regulatory Element Binding Protein 1/metabolism/genetics ; }, abstract = {BACKGROUND: Yellow leaf green tea (YLGT) is a new variety of Camellia sinensis (L.) O. Ktze, which has yellow leaves and the unique qualities of 'three green through three yellow'. The present study aimed to investigate the anti-obesity effect of YLGT in mice fed a high-fat diet (HFD) and to explore the potential mechanisms by regulating the AMPK/ACC/SREBP1c signaling pathways and gut microbiota.<br><br>RESULTS: The results showed that YLGT aqueous extract reduced body weight, hepatic inflammation, fat accumulation and hyperlipidemia in HFD-induced C57BL/6J mice, and also accelerated energy metabolism, reduced fat synthesis and suppressed obesity by activating the AMPK/CPT-1&#x3b1; signaling pathway and inhibiting the FAS/ACC/SREBP-1c signaling pathway. Fecal microbiota transplantation experiment further confirmed that the alteration of gut microbiota (e.g. increasing unclassified_Muribaculaceae and decreasing Colidextribacter) might be an important cause of YLGT water extract inhibiting obesity.<br><br>CONCLUSION: In conclusion, YLGT has a broad application prospect in the treatment of obesity and the development of anti-obesity function beverages. &#xa9; 2024 Society of Chemical Industry.}, }
@article {pmid38407164, year = {2024}, author = {Mena, CJ and Garófalo, MP and Perazzo, J and Epelbaum, C and Castro, G and Sicilia, P and Barnes, A and Guasconi, L and Burstein, VL and Beccacece, I and Almeida, MA and Cervi, L and Santin, M and Chiapello, LS}, title = {Enterocytozoon bieneusi Infection after Hematopoietic Stem Cell Transplant in Child, Argentina.}, journal = {Emerging infectious diseases}, volume = {30}, number = {3}, pages = {613-616}, pmid = {38407164}, issn = {1080-6059}, mesh = {Humans ; Child ; Argentina/epidemiology ; *Enterocytozoon/genetics ; Transplant Recipients ; Feces ; *Hematopoietic Stem Cell Transplantation/adverse effects ; }, abstract = {We report a case of Enterocytozoon bieneusi infection in a pediatric hematopoietic stem cell transplant recipient in Argentina. Spores were visualized in feces using Calcofluor White and modified trichrome stainings. PCR and sequencing identified E. bieneusi genotype D in fecal samples and liver samples, confirming extraintestinal dissemination of the parasite.}, }
@article {pmid38405608, year = {2024}, author = {Lu, X and Yang, R and Chen, Y and Chen, D}, title = {NAD metabolic therapy in metabolic dysfunction-associated steatotic liver disease: Possible roles of gut microbiota.}, journal = {iScience}, volume = {27}, number = {3}, pages = {109174}, pmid = {38405608}, issn = {2589-0042}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly named non-alcoholic fatty liver disease (NAFLD), is induced by alterations of hepatic metabolism. As a critical metabolites function regulator, nicotinamide adenine dinucleotide (NAD) nowadays has been validated to be effective in the treatment of diet-induced murine model of MASLD. Additionally, gut microbiota has been reported to have the potential to prevent MASLD by dietary NAD precursors metabolizing together with mammals. However, the underlying mechanism remains unclear. In this review, we hypothesized that NAD enhancing mitochondrial activity might reshape a specific microbiota signature, and improve MASLD progression demonstrated by fecal microbiota transplantation. Here, this review especially focused on the mechanism of Microbiota-Gut-Liver Axis together with NAD metabolism for the MASLD progress. Notably, we found significant changes in Prevotella associated with NAD in a gut microbiome signature of certain MASLD patients. With the recent researches, we also inferred that Prevotella can not only regulate the level of NAD pool by boosting the carbon metabolism, but also play a vital part in regulating the branched-chain amino acid (BCAA)-related fatty acid metabolism pathway. Altogether, our results support the notion that the gut microbiota contribute to the dietary NAD precursors metabolism in MASLD development and the dietary NAD precursors together with certain gut microbiota may be a preventive or therapeutic strategy in MASLD management.}, }
@article {pmid38405047, year = {2024}, author = {Kopera, AF and Khiew, YC and Amer Alsamman, M and Mattar, MC and Olsen, RS and Doman, DB}, title = {Depression and the Aberrant Intestinal Microbiome.}, journal = {Gastroenterology &amp; hepatology}, volume = {20}, number = {1}, pages = {30-40}, pmid = {38405047}, issn = {1554-7914}, abstract = {Depression is one of the most common mental health disorders affecting adults in the United States. The current treatment is the combination of pharmacotherapy and psychotherapy. Recently, the evidence linking gut microbiome dysregulation to the development of depression has grown. The pathophysiology is currently poorly understood, although leading hypotheses include involvement of the hypothalamic-pituitary-adrenal axis, a bidirectional relationship between the gut microbiome and the central nervous system, and production of signaling molecules by the gut microbiome. Available and emerging treatments of the aberrant microbiome include antidepressants, antibiotics, diet modification, probiotics, and fecal microbiota transplant. This article explores the interconnectivity of gut microbiota and depression and treatments targeted toward the gut, reviews the gastroenterologist's potential role in managing gut dysbiosis in patients with depression, and highlights research topics to be addressed to create evidence-based guidelines.}, }
@article {pmid38404132, year = {2024}, author = {Joo, MK and Lee, JW and Woo, JH and Kim, HJ and Kim, DH and Choi, JH}, title = {Regulation of colonic neuropeptide Y expression by the gut microbiome in patients with ulcerative colitis and its association with anxiety- and depression-like behavior in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2319844}, pmid = {38404132}, issn = {1949-0984}, mesh = {Humans ; Anxiety ; *Colitis, Ulcerative/microbiology ; Depression ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Neuropeptide Y/genetics ; Animals ; Mice ; }, abstract = {Patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC), show an increased incidence of anxiety and depression; however, the association between UC-associated psychiatric disorders and the gut microbiota is unclear. This study aimed to examine whether gut microbiota from patients with UC can alter colonic gene expression, leading to anxiety- and depression-like behavior in mice receiving fecal microbiota transplantation (FMT). RNA sequencing transcriptome analyses revealed a difference in colonic gene expression between mice receiving FMT from patients with UC (UC-FMT mice) and those receiving FMT from healthy controls (HC-FMT mice). Gene ontology analysis revealed the downregulation of neuropeptide signaling pathways, including neuropeptide Y (NPY) expression, in the colons of UC-FMT mice. The protein levels of NPY also decreased in the colon and plasma of UC-FMT mice compared to those in HC-FMT mice. The oral administration of Enterococcus mundtii (EM), a bacterium isolated from the feces of patients with UC, reduced NPY expression in the colons of mice and induced intestinal inflammation, anxiety, and depression-like behavior. Reduced NPY protein levels were also observed in the plasma and hippocampus of EM-treated mice. Intraperitoneal administration of NPY significantly alleviated anxiety- and depressive-like behaviors induced by EM in mice. Capsular polysaccharide in EM was associated with EM-induced NPY downregulation in the colon. Analysis of Gene Expression Omnibus datasets showed markedly reduced NPY expression in the inflamed colons of patients with UC compared with that in the colons of healthy controls. In summary, EM-induced reduction in the colonic expression of NPY may be associated with a decrease in hippocampal NPY and anxiety- and depression-like behavior in mice.}, }
@article {pmid38402605, year = {2024}, author = {Ijeomah, IM and Temitope, FOC and Lander, C and Sheriff, AT and Uwem, GE and Bernard, OA and Oluseyi, OA and Elijah, OI and Toluwani, AG and Arthur, OO and Toluwanimi, AE and Bolutife, PO and Damilola, OG and Titilola, OO and Oluwadamilola, GA and Muhammad, AI and Omotosho, KI and Johnson, AA and Jelle, M and Olubusuyi, AM}, title = {Classic human astrovirus 4, 8, MLB-3, and likely new genotype 5 sublineage in stool samples of children in Nigeria.}, journal = {Journal of medical virology}, volume = {96}, number = {3}, pages = {e29489}, doi = {10.1002/jmv.29489}, pmid = {38402605}, issn = {1096-9071}, mesh = {Child ; Humans ; Aged ; *Mamastrovirus/genetics ; Phylogeny ; Nigeria/epidemiology ; *Astroviridae Infections/epidemiology ; Feces ; Genotype ; }, abstract = {Human astrovirus (HAstV) is a nonenveloped RNA virus and has been implicated in acute gastroenteritis among children and elderly. However, there exists a substantial dearth of information on HAstV strains circulating in Nigeria. Viral-like particles were purified from archived 254 stool samples of children with acute flaccid paralysis between January and December 2020 from five states in Nigeria, using the NetoVIR protocol. Extracted viral RNA and DNA were subjected to a reverse transcription step and subsequent random polymerase chain reaction amplification. Library preparation and Illumina sequencing were performed. Using the virome paired-end reads pipeline, raw reads were processed into genomic contigs. Phylogenetic and pairwise identity analysis of the recovered HAstV genomes was performed. Six near-complete genome sequences of HAstV were identified and classified as HAstV4 (n = 1), HAstV5 (n = 1), HAstV8 (n = 1), and MLB-3 (n = 3). The HAstV5 belonged to a yet unclassified sublineage, which we tentatively named HAstV-5d. Phylogenetic analysis of open reading frames 1a, 1b, and 2 suggested recombination events inside the MAstV1 species. Furthermore, phylogenetic analysis implied a geographic linkage between the HAstV5 strain from this study with two strains from Cameroon across all the genomic regions. We report for the first time the circulation of HAstV genotypes 4, 8, and MLB-3 in Nigeria and present data suggestive for the existence of a new sublineage of HAstV5. To further understand the burden, diversity, and evolution of HAstV, increased research interest as well as robust HAstV surveillance in Nigeria is essential.}, }
@article {pmid38402460, year = {2024}, author = {Zhu, Y and He, H and Sun, W and Wu, J and Xiao, Y and Peng, Y and Hu, P and Jin, M and Liu, P and Zhang, D and Xie, T and Huang, L and He, W and Wei, M and Wang, L and Xu, X and Tang, Y}, title = {IgA nephropathy: gut microbiome regulates the production of hypoglycosilated IgA1 via the TLR4 signaling pathway.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {39}, number = {10}, pages = {1624-1641}, pmid = {38402460}, issn = {1460-2385}, support = {82304948//National Natural Science Foundation of China/ ; 2022MHZ004//Natural Science Foundation in Minhang District of Shanghai/ ; 2022MW13//Research project of Shanghai Minhang District Health Committee/ ; 2020MZYS19//Minhang District High-Level Specialty Key Physician Training Program/ ; 2020MWTZB07//Minhang District Medical Characteristic Specialty Project/ ; YJXK-2021-13//Hospital-level Discipline-Chronic Disease Group-Chronic Kidney Disease Project/ ; //Jiangsu Provincial Medical Innovation Center/ ; }, mesh = {Adult ; Animals ; Female ; Humans ; Male ; Mice ; Middle Aged ; Case-Control Studies ; *Gastrointestinal Microbiome ; *Glomerulonephritis, IGA/microbiology/metabolism/immunology/pathology ; *Immunoglobulin A/metabolism ; Mice, Inbred C57BL ; *Signal Transduction ; *Toll-Like Receptor 4/metabolism ; }, abstract = {BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a major cause of primary glomerulonephritis characterized by mesangial deposits of galactose-deficient IgA1 (Gd-IgA1). Toll-like receptors (TLRs), particularly TLR4, are involved in the pathogenesis of IgAN. The role of gut microbiota on IgAN patients was recently investigated. However, whether gut microbial modifications of Gd-IgA1 through TLR4 play a role in IgAN remains unclear.<br><br>METHODS: We recruited subjects into four groups, including 48 patients with untreated IgAN, 22 treated IgAN patients (IgANIT), 22 primary membranous nephropathy and 31 healthy controls (HCs). Fecal samples were collected to analyze changes in gut microbiome. Gd-IgA1 levels, expression of TLR4, B-cell stimulators and intestinal barrier function were evaluated in all subjects. C57BL/6 mice were treated with a broad-spectrum antibiotic cocktail to deplete the gut microbiota and then gavaged with fecal microbiota transplanted from clinical subjects of every group. Gd-IgA1 and TLR4 pathway were detected in peripheral blood mononuclear cells (PBMCs) from IgAN and HCs co-incubated with lipopolysaccharide (LPS) and TLR4 inhibitor.<br><br>RESULTS: Compared with the other three groups, different compositions and decreased diversity demonstrated gut dysbiosis in the untreated IgAN group, especially the enrichment of Escherichia-Shigella. Elevated Gd-IgA1 levels were found in untreated IgAN patients and correlated with gut dysbiosis, TLR4, B-cell stimulators, indexes of intestinal barrier damage and proinflammatory cytokines. In vivo, mice colonized with gut microbiota from IgAN and IgANIT patients mimicked the IgAN phenotype with the activation of TLR4/MyD88/nuclear factor-&#x3ba;B pathway and B-cell stimulators in the intestine, and had with enhanced proinflammatory cytokines. In vitro, LPS activated TLR4/MyD88/NF-&#x3ba;B pathway, B-cell stimulators and proinflammatory cytokines in PBMCs of IgAN patients. This process may induce the overproduction of Gd-IgA1, which was inhibited by TLR4 inhibitors.<br><br>CONCLUSIONS: Our results illustrated that the gut-kidney axis is involved in the pathogenesis of IgAN. Gut dysbiosis could stimulate the overproduction of Gd-IgA1 via TLR4 signaling pathway production and B-cell stimulators.}, }
@article {pmid38400885, year = {2024}, author = {Chen, X and Wang, G and Qin, L and Hu, B and Li, J}, title = {Intestinal Microbiota Modulates the Antitumor Effect of Oncolytic Virus Vaccines in Colorectal Cancer.}, journal = {Digestive diseases and sciences}, volume = {69}, number = {4}, pages = {1228-1241}, pmid = {38400885}, issn = {1573-2568}, support = {22NSFCS1601//Department of Science and Technology of Sichuan Province/ ; }, mesh = {Humans ; Animals ; Mice ; *Oncolytic Viruses/genetics ; *Gastrointestinal Microbiome/physiology ; CD8-Positive T-Lymphocytes/metabolism ; *Colorectal Neoplasms/pathology ; DNA, Ribosomal/pharmacology ; }, abstract = {BACKGROUND: Immunotherapies, such as oncolytic viruses, have become powerful cancer treatments, but only some patients with cancer can benefit from them, especially those with advanced-stage cancer, and new therapeutic strategies are needed to facilitate extended survival. The intestinal microbiota may contribute to colorectal cancer (CRC) carcinogenesis and the response to immunotherapy. However, whether and how the intestinal microbiota modulates the effects of oncolytic virus vaccines (OVVs) in CRC remain to be investigated.<br><br>METHODS: We generated an MC38-gp33 CRC mouse model and treated it with OVV-gp33 in early and advanced stages. Probiotics, fecal microbiota transplantation (FMT), and antibiotics (ABX) were administered to regulate the microbial composition of CRC mice at an advanced stage. The tumor growth rate and survival time of the mice were recorded; 16S rDNA sequencing was used to analyze the microbial composition and flow cytometry was used to detect T-cell subset activity.<br><br>RESULTS: OVV-gp33 treatment inhibited tumor growth and prolonged survival in the early stage of CRC but&#xa0;did not have a significant effect on the advanced stage of CRC. Moreover, 16S rDNA sequence analysis and flow cytometry showed significant differences in intestinal microbiota composition, microbial metabolites, and T-cell subsets in early and advanced-stage CRC. Probiotic and FMT treatment significantly enhanced the antitumor effect of OVV in the advanced stage of CRC with an increased abundance of activated CD8[+] T cells and a decreased ratio of Treg cells, while depletion of the microbiota by ABX eliminated the antitumor activity of OVV with decreased CD8[+] T-cell activation and upregulated Treg cells.<br><br>CONCLUSIONS: These results indicate that the intestinal microbiota and microbial metabolites play an important role in the antitumor effect of OVV in CRC. Furthermore, altering the intestinal microbiota composition can modulate the antitumor and immunomodulatory effects of OVV in CRC.}, }
@article {pmid38400752, year = {2024}, author = {He, Z and Xie, H and Xu, H and Wu, J and Zeng, W and He, Q and Jobin, C and Jin, S and Lan, P}, title = {Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2319511}, pmid = {38400752}, issn = {1949-0984}, mesh = {Humans ; Mice ; Animals ; Oxaliplatin/toxicity ; Interleukin-10/genetics ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Macrophages ; *Probiotics/pharmacology/therapeutic use ; *Antineoplastic Agents/adverse effects ; }, abstract = {The gut microbiota has been shown to influence the efficacy and toxicity of chemotherapy, thereby affecting treatment outcomes. Understanding the mechanism by which microbiota affects chemotherapeutic toxicity would have a profound impact on cancer management. In this study, we report that fecal microbiota transplantation from oxaliplatin-exposed mice promotes toxicity in recipient mice. Splenic RNA sequencing and macrophage depletion experiment showed that the microbiota-induced toxicity of oxaliplatin in mice was dependent on macrophages. Furthermore, oxaliplatin-mediated toxicity was exacerbated in Il10[-/-] mice, but not attenuated in Rag1[-/-] mice. Adoptive transfer of macrophage into Il10[-/-] mice confirmed the role of macrophage-derived IL-10 in the improvement of oxaliplatin-induced toxicity. Depletion of fecal Lactobacillus and Bifidobacterium was associated with the exacerbation of oxaliplatin-mediated toxicity, whereas supplementation with these probiotics alleviated chemotherapy-induced toxicity. Importantly, IL-10 administration and probiotics supplementation did not attenuate the antitumor efficacy of chemotherapy. Clinically, patients with colorectal cancer exposed to oxaliplatin exhibited downregulation of peripheral CD45[+]IL-10[+] cells. Collectively, our findings indicate that microbiota-mediated IL-10 production influences tolerance to chemotherapy, and thus represents a potential clinical target.}, }
@article {pmid38400709, year = {2024}, author = {de Wit, S and Geerlings, L and Shi, C and Dronkers, J and Schouten, EM and Blancke, G and Andries, V and Yntema, T and Meijers, WC and Koonen, DPY and Vereecke, L and Silljé, HHW and Aboumsallem, JP and de Boer, RA}, title = {Heart failure-induced microbial dysbiosis contributes to colonic tumour formation in mice.}, journal = {Cardiovascular research}, volume = {120}, number = {6}, pages = {612-622}, pmid = {38400709}, issn = {1755-3245}, support = {/ERC_/European Research Council/International ; }, mesh = {Animals ; *Dysbiosis ; *Mice, Inbred C57BL ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Disease Models, Animal ; *Myocardial Infarction/pathology/microbiology ; *Heart Failure/microbiology/pathology/etiology ; Male ; *Colon/microbiology/pathology ; Ribotyping ; Colonic Neoplasms/pathology/microbiology ; Bacteria/genetics ; Feces/microbiology ; Host-Pathogen Interactions ; }, abstract = {AIMS: Heart failure (HF) and cancer are the leading causes of death worldwide. Epidemiological studies revealed that HF patients are prone to develop cancer. Preclinical studies provided some insights into this connection, but the exact mechanisms remain elusive. In colorectal cancer (CRC), gut microbial dysbiosis is linked to cancer progression and recent studies have shown that HF patients display microbial dysbiosis. This current study focussed on the effects of HF-induced microbial dysbiosis on colonic tumour formation.<br><br>METHODS AND RESULTS: C57BL/6J mice were subjected to myocardial infarction (MI), with sham surgery as control. After six weeks faeces were collected, processed for 16&#x2005;s rRNA sequencing, and pooled for faecal microbiota transplantation. CRC tumour growth was provoked in germ-free mice by treating them with Azoxymethane/Dextran sodium sulphate. The CRC mice were transplanted with faeces from MI or sham mice. MI-induced HF resulted in microbial dysbiosis, characterized by a decreased &#x3b1;-diversity and microbial alterations on the genus level, several of which have been associated with CRC. We then performed faecal microbiota transplantation with faeces from HF mice in CRC mice, which resulted in a higher endoscopic disease score and an increase in the number of tumours in CRC mice.<br><br>CONCLUSION: We demonstrated that MI-induced HF contributes to colonic tumour formation by altering the gut microbiota composition, providing a mechanistic explanation for the observed association between HF and increased risk for cancer. Targeting the microbiome may present as a tool to mitigate HF-associated co-morbidities, especially cancer.}, }
@article {pmid38399665, year = {2024}, author = {Raymo, G and Ali, A and Ahmed, RO and Salem, M}, title = {Early-Life Fecal Transplantation from High Muscle Yield Rainbow Trout to Low Muscle Yield Recipients Accelerates Somatic Growth through Respiratory and Mitochondrial Efficiency Modulation.}, journal = {Microorganisms}, volume = {12}, number = {2}, pages = {}, pmid = {38399665}, issn = {2076-2607}, support = {2023-67015-39742//National Institute of Food and Agriculture/ ; }, abstract = {Previous studies conducted in our lab revealed microbial assemblages to vary significantly between high (ARS-FY-H) and low fillet yield (ARS-FY-L) genetic lines in adult rainbow trout. We hypothesized that a high ARS-FY-H donor microbiome can accelerate somatic growth in microbiome-depleted rainbow trout larvae of the ARS-FY-L line. Germ-depleted larvae of low ARS-FY-L line trout reared in sterile environments were exposed to high- or low-fillet yield-derived microbiomes starting at first feeding for 27 weeks. Despite weight-normalized diets, somatic mass was significantly increased in larvae receiving high fillet yield microbiome cocktails at 27 weeks post-hatch. RNA-seq from fish tails reveals enrichment in NADH dehydrogenase activity, oxygen carrier, hemoglobin complex, gas transport, and respiratory pathways in high fillet yield recolonized larvae. Transcriptome interrogation suggests a relationship between electron transport chain inputs and body weight assimilation, mediated by the gut microbiome. These findings suggest that microbiome payload originating from high fillet yield adult donors primarily accelerates juvenile somatic mass assimilation through respiratory and mitochondrial input modulation. Further microbiome studies are warranted to assess how increasing beneficial microbial taxa could be a basis for formulating appropriate pre-, pro-, or post-biotics in the form of feed additives and lead to fecal transplantation protocols for accelerated feed conversion and fillet yield in aquaculture.}, }
@article {pmid38399561, year = {2024}, author = {Di Leo, V and Annese, F and Papadia, F and Russo, MS and Giliberti, M and Sallustio, F and Gesualdo, L}, title = {Refractory IgA Nephropathy: A Challenge for Future Nephrologists.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {2}, pages = {}, pmid = {38399561}, issn = {1648-9144}, mesh = {Humans ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; *Glomerulonephritis, IGA/drug therapy ; Angiotensin Receptor Antagonists/therapeutic use ; Nephrologists ; Antihypertensive Agents/therapeutic use ; *Kidney Failure, Chronic/therapy ; Steroids/therapeutic use ; Immunosuppressive Agents/therapeutic use ; }, abstract = {IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin-angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.}, }
@article {pmid38398873, year = {2024}, author = {Suprunowicz, M and Tomaszek, N and Urbaniak, A and Zackiewicz, K and Modzelewski, S and Waszkiewicz, N}, title = {Between Dysbiosis, Maternal Immune Activation and Autism: Is There a Common Pathway?.}, journal = {Nutrients}, volume = {16}, number = {4}, pages = {}, pmid = {38398873}, issn = {2072-6643}, mesh = {Child ; Humans ; *Autism Spectrum Disorder/etiology/metabolism ; *Autistic Disorder/etiology ; Dysbiosis/complications ; *Gastrointestinal Microbiome/physiology ; Family ; Bacteria ; }, abstract = {Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut-brain-microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother's obesity as potentially environmental factors of ASD. The purpose of this review is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.}, }
@article {pmid38397562, year = {2024}, author = {Cheng, N and Wang, X and Zhou, Y and Zhao, X and Chen, M and Zhao, H and Cao, W}, title = {Schisandra chinensis Bee Pollen Ameliorates Colitis in Mice by Modulating Gut Microbiota and Regulating Treg/Th17 Balance.}, journal = {Foods (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, pmid = {38397562}, issn = {2304-8158}, support = {2022YFD1600205//the National Key Research and Development Program of China/ ; No. 32372428//the National Natural Science Foundation of China/ ; TZ0389//the Shaanxi high-level talent special support plan/ ; 23KGDW0010-2023//the Xi'an Science&amp; Technology Project/ ; }, abstract = {Colitis is a chronic disease associated with alterations in the composition of gut microbiota. Schisandra chinensis bee pollen extract (SCPE) has been proved to be rich in phenolic compounds and effective in modulating gut microbiota, but its effect on colitis and the underlying mechanism remains unclear. This study investigates the relationship between colitis amelioration and the gut microbiota regulation of SCPE via fecal microbial transplantation (FMT). The results showed that administration of 20.4 g/kg BW of SCPE could primely ameliorate colitis induced by dextran sulfate sodium (DSS) in mice, showing as more integration of colon tissue structure and the colonic epithelial barrier, as well as lower oxidative stress and inflammation levels compared with colitis mice. Moreover, SCPE supplement restored the balance of T regulatory (Treg) cells and T helper 17 (Th17) cells. Gut microbiota analysis showed SCPE treatment could reshape the gut microbiota balance and improve the abundance of gut microbiota, especially the beneficial bacteria (Akkermansia and Lactobacillus) related to the production of short-chain fatty acids and the regulation of immunity. Most importantly, the protection of 20.4 g/kg BW of SCPE on colitis can be perfectly transmitted by fecal microbiota. Therefore, the gut microbiota-SCFAS-Treg/Th17 axis can be the main mechanism for SCPE to ameliorate colitis. This study suggests that SCPE can be a new promising functional food for prevention and treatment of colitis by reshaping gut microbiota and regulating gut immunity.}, }
@article {pmid38395525, year = {2024}, author = {Peery, AF and Kelly, CR and Kao, D and Vaughn, BP and Lebwohl, B and Singh, S and Imdad, A and Altayar, O and , }, title = {AGA Clinical Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases.}, journal = {Gastroenterology}, volume = {166}, number = {3}, pages = {409-434}, doi = {10.1053/j.gastro.2024.01.008}, pmid = {38395525}, issn = {1528-0012}, mesh = {Adult ; Humans ; *Irritable Bowel Syndrome/drug therapy ; *Clostridioides difficile ; Treatment Outcome ; *Gastrointestinal Diseases/therapy/drug therapy ; Fecal Microbiota Transplantation/adverse effects ; *Inflammatory Bowel Diseases/drug therapy ; *Clostridium Infections/therapy/drug therapy ; Anti-Bacterial Agents/therapeutic use ; *Microbiota ; Recurrence ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota-based therapies include conventional fecal microbiota transplant and US Food and Drug Administration-approved therapies, fecal microbiota live-jslm and fecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of fecal microbiota-based therapies in adults with recurrent Clostridioides difficile infection; severe to fulminant C difficile infection; inflammatory bowel diseases, including pouchitis; and irritable bowel syndrome.<br><br>METHODS: The&#xa0;guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of fecal microbiota-based therapies in the specified gastrointestinal conditions and provided implementation considerations for clinical practice.<br><br>RESULTS: The guideline panel made 7 recommendations. In immunocompetent adults with recurrent C difficile infection, the AGA suggests select use of fecal microbiota-based therapies on completion of standard of care antibiotics to prevent recurrence. In mildly or moderately immunocompromised adults with recurrent C difficile infection, the AGA suggests select use of conventional fecal microbiota transplant. In severely immunocompromised adults, the AGA suggests against the use of any fecal microbiota-based therapies to prevent recurrent C difficile. In adults hospitalized with severe or fulminant C difficile not responding to standard of care antibiotics, the AGA suggests select use of conventional fecal microbiota transplant. The AGA suggests against the use of conventional fecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials.<br><br>CONCLUSIONS: Fecal microbiota-based therapies are effective therapy to prevent recurrent C difficile in select patients. Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.}, }
@article {pmid38392196, year = {2024}, author = {Tao, W and Fan, Q and Wei, J}, title = {Gut-Liver Axis as a Therapeutic Target for Drug-Induced Liver Injury.}, journal = {Current issues in molecular biology}, volume = {46}, number = {2}, pages = {1219-1236}, pmid = {38392196}, issn = {1467-3045}, support = {2021-620-000-001-021//Hubei Innovation Center of Agricultural Science and Technology/ ; 2024NKYJJ17//Youth Foundation of Hubei Academy of Agricultural Sciences/ ; }, abstract = {Drug-induced liver injury (DILI) is a liver disease that remains difficult to predict and diagnose, and the underlying mechanisms are yet to be fully clarified. The gut-liver axis refers to the reciprocal interactions between the gut and the liver, and its homeostasis plays a prominent role in maintaining liver health. It has been recently reported that patients and animals with DILI have a disrupted gut-liver axis, involving altered gut microbiota composition, increased intestinal permeability and lipopolysaccharide translocation, decreased short-chain fatty acids production, and impaired bile acid metabolism homeostasis. The present review will summarize the evidence from both clinical and preclinical studies about the role of the gut-liver axis in the pathogenesis of DILI. Moreover, we will focus attention on the potential therapeutic strategies for DILI based on improving gut-liver axis function, including herbs and phytochemicals, probiotics, fecal microbial transplantation, postbiotics, bile acids, and Farnesoid X receptor agonists.}, }
@article {pmid38391047, year = {2024}, author = {Lauwers, E and Sabino, J and Hoffman, I and van Hoeve, K}, title = {Faecal microbiota transplantation in children: A systematic review.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {113}, number = {9}, pages = {1991-2002}, doi = {10.1111/apa.17167}, pmid = {38391047}, issn = {1651-2227}, support = {//Fonds Wetenschappelijk Onderzoek/ ; //Viatris/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Child ; *Clostridium Infections/therapy ; Gastrointestinal Microbiome ; }, abstract = {AIM: Novel technologies offer insights into the potential role of the intestinal microbiota in human health and disease. Dysbiosis has been associated with several diseases, and it is thought to play a role in the pathogenesis of different gastrointestinal diseases. Faecal microbiota transplantation (FMT) is emerging as a method to modulate the gastrointestinal microbial ecosystem. While recurrent Clostridioides difficile infection is the recognised FMT indication, exploration of other therapeutic uses is ongoing.<br><br>METHODS: Following PRISMA guidelines, we conducted a systematic review, extracting 583 articles from Embase and PubMed (index date to October 2022).<br><br>RESULTS: The search yielded 58 studies for full review, with 50 included in the systematic review. Articles were categorised by FMT indication, study design, efficacy, adverse events, donor selection and administration route. FMT appears safe and effective for recurrent Clostridioides difficile infection, although severe adverse events are reported in children. However, there are currently insufficient data to support the use of FMT for other potential therapeutic indications (such as irritable or inflammatory bowel disease or obesity), beside the potential to decolonise multi-drug resistant organisms.<br><br>CONCLUSION: This underscores the need for randomised, controlled, prospective cohort studies in children to assess FMT effectiveness in diverse conditions and counteract publication bias.}, }
@article {pmid38390942, year = {2024}, author = {Jirillo, E and Palmirotta, R and Colella, M and Santacroce, L}, title = {A Bird's-Eye View of the Pathophysiologic Role of the Human Urobiota in Health and Disease: Can We Modulate It?.}, journal = {Pathophysiology : the official journal of the International Society for Pathophysiology}, volume = {31}, number = {1}, pages = {52-67}, pmid = {38390942}, issn = {1873-149X}, abstract = {For a long time, urine has been considered sterile in physiological conditions, thanks to the particular structure of the urinary tract and the production of uromodulin or Tamm-Horsfall protein (THP) by it. More recently, thanks to the development and use of new technologies, i.e., next-generation sequencing and expanded urine culture, the identification of a microbial community in the urine, the so-called urobiota, became possible. Major phyla detected in the urine are represented by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Particularly, the female urobiota is largely represented by Lactobacillus spp., which are very active against urinary pathogenic Escherichia (E.) coli (UPEC) strains via the generation of lactic acid and hydrogen peroxide. Gut dysbiosis accounts for recurrent urinary tract infections (UTIs), so-called gut-bladder axis syndrome with the formation of intracellular bacterial communities in the course of acute cystitis. However, other chronic urinary tract infections are caused by bacterial strains of intestinal derivation. Monomicrobial and polymicrobial infections account for the outcome of acute and chronic UTIs, even including prostatitis and chronic pelvic pain. E. coli isolates have been shown to be more invasive and resistant to antibiotics. Probiotics, fecal microbial transplantation, phage therapy, antimicrobial peptides, and immune-mediated therapies, even including vaccines for the treatment of UTIs, will be described.}, }
@article {pmid38389631, year = {2024}, author = {Franco, CD and Sagar, RS and Bokhari, SFH}, title = {From Microbes to Memories: Challenges and Future Perspectives Regarding the Gut-Brain Axis for Improved Cognitive Health in Alzheimer's.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e52795}, pmid = {38389631}, issn = {2168-8184}, abstract = {The gut-brain axis, a bidirectional communication network between the gastrointestinal tract and the central nervous system, regulates various physiological processes crucial for health, including immune response, metabolism, and neurotransmitter production. In the context of neurodegenerative diseases, especially Alzheimer's disease (AD), understanding the intricate connection of the gut-brain axis has gained significance. Disturbances along this axis have been implicated in neurodegenerative diseases, emphasizing its role in AD pathogenesis. Microbiota dysbiosis, influenced by diet, lifestyle, and genetics, contributes to altered gut permeability, leading to protein dyshomeostasis, astroglial activation, neuroinflammation, and cognitive decline. Understanding these mechanisms is crucial for developing interventions to restore a healthy gut microbiota and potentially mitigate AD-related cognitive decline. The bidirectional communication along the gut-brain axis involves microbial metabolites, influencing oxidative stress, protein aggregation, and other pathways linked to neuroprotection. Modulating the gut microbiota through dietary changes, prebiotics, probiotics, or fecal microbiota transplantation emerges as a promising approach to target cognitive decline in AD. Despite progress, challenges persist, including the correlational nature of studies, the complexity of the gut microbiome, and variations in methodologies. Standardization is essential for reliable findings and the identification of biomarkers associated with AD. Unanswered questions warrant further exploration, particularly in understanding specific mechanisms, the temporal dynamics of microbiota changes, and the influence of diet and lifestyle on the gut-brain axis in AD. Future perspectives involve promising therapeutic interventions targeting the gut-brain axis, emphasizing personalized medicine to optimize outcomes based on individual variations in the gut-brain axis characteristics.}, }
@article {pmid38389170, year = {2024}, author = {Lyu, X and Zhang, TT and Ye, Z and Chen, C}, title = {Astragaloside IV Mitigated Diabetic Nephropathy by Restructuring Intestinal Microflora and Ferroptosis.}, journal = {Molecular nutrition &amp; food research}, volume = {68}, number = {6}, pages = {e2300734}, doi = {10.1002/mnfr.202300734}, pmid = {38389170}, issn = {1613-4133}, support = {Q202147//Jiangsu Provincial Pharmaceutical Society-Tianqing Hospital Pharmacy Fund/ ; }, mesh = {Mice ; Animals ; *Diabetic Nephropathies/drug therapy ; *Gastrointestinal Microbiome ; *Ferroptosis ; Kidney ; *Diabetes Mellitus ; *Saponins ; *Triterpenes ; }, abstract = {SCOPE: To investigate the underlying mechanism of Astragaloside IV (AS-IV) in ameliorating diabetic nephropathy (DN) by regulating intestinal microbiota ecology and intestinal mucosal barrier.<br><br>METHODS AND RESULTS: Genetically db/db mice are used to establish DN mouse model to monitor the therapeutic effects of AS-IV and fecal microbiota transplantation (FMT) against DN. Supplementation with AS-IV dramatically attenuates several clinical indicators of DN in db/db mice. In addition, AS-IV markedly improves intestinal barrier function, modifies intestinal permeability, and reduces inflammation. Moreover, AS-IV treatment remarkably improves intestinal dysbiosis in db/db mice, characterized by an elevated abundance of Akkermansia, Ligilactobacillus, and Lactobacillus, indicating the fundamental role of the microbiome in DN progression. Furthermore, FMT derived from AS-IV-treated db/db mice is potentially efficient in antagonizing renal dysfunction, rebalancing gut microbiota, and improving intestinal permeability in recipient db/db mice. AS-IV-enriched Akkermansia muciniphila dramatically alleviates DN and intestinal mucosal barrier dysfunction in db/db mice. Intriguingly, AS-IV intervention dramatically diminishes ferroptosis in the kidney and colon tissues. CONCLUSION&#xa0;: Intestinal microbiome alterations and ferroptosis modulation by AS-IV may play instrumental roles in this mechanism, providing compelling evidence for the role of the gut-renal axis in DN.}, }
@article {pmid38388538, year = {2024}, author = {Cao, Z and Fan, D and Sun, Y and Huang, Z and Li, Y and Su, R and Zhang, F and Li, Q and Yang, H and Zhang, F and Miao, Y and Lan, P and Wu, X and Zuo, T}, title = {The gut ileal mucosal virome is disturbed in patients with Crohn's disease and exacerbates intestinal inflammation in mice.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {1638}, pmid = {38388538}, issn = {2041-1723}, support = {82172323//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32100134//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82060107//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; Animals ; Mice ; *Crohn Disease/pathology ; Virome ; *Inflammatory Bowel Diseases/pathology ; Intestinal Mucosa/metabolism ; Ileum/pathology ; *Bacteriophages ; Bacteria ; Inflammation/pathology ; }, abstract = {Gut bacteriome dysbiosis is known to be implicated in the pathogenesis of inflammatory bowel disease (IBD). Crohn's disease (CD) is an IBD subtype with extensive mucosal inflammation, yet the mucosal virome, an empirical modulator of the bacteriome and mucosal immunity, remains largely unclear regarding its composition and role. Here, we exploited trans-cohort CD patients and healthy individuals to compositionally and functionally investigate the small bowel (terminal ileum) virome and bacteriome. The CD ileal virome was characterised by an under-representation of both lytic and temperate bacteriophages (especially those targeting bacterial pathogens), particularly in patients with flare-up. Meanwhile, the virome-bacteriome ecology in CD ileal mucosa was featured by a lack of Bifidobacterium- and Lachnospiraceae-led mutualistic interactions between bacteria and bacteriophages; surprisingly it was more pronounced in CD remission than flare-up, underlining the refractory and recurrent nature of mucosal inflammation in CD. Lastly, we substantiated that ileal virions from CD patients causally exacerbated intestinal inflammation in IBD mouse models, by reshaping a gut virome-bacteriome ecology preceding intestinal inflammation (microbial trigger) and augmenting microbial sensing/defence pathways in the intestine cells (host response). Altogether, our results highlight the significance of mucosal virome in CD pathogenesis and importance of mucosal virome restoration in CD therapeutics.}, }
@article {pmid38388458, year = {2024}, author = {Yang, J and Liu, W and Han, X and Hao, X and Yao, Q and Du, W}, title = {Gut microbiota modulation enhances the immune capacity of lizards under climate warming.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {37}, pmid = {38388458}, issn = {2049-2618}, support = {32301304//National Natural Science Foundation of China/ ; 31821001//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Lizards/microbiology ; Climate Change ; Bacteria/genetics ; Anti-Bacterial Agents ; }, abstract = {BACKGROUND: Host-microbial interactions are expected to affect species' adaptability to climate change but have rarely been explored in ectothermic animals. Some studies have shown that short-term warming reduced gut microbial diversity that could hamper host functional performance.<br><br>RESULTS: However, our longitudinal experiments in semi-natural conditions demonstrated that warming decreased gut microbiota diversity at 2&#xa0;months, but increased diversity at 13 and 27&#xa0;months in a desert lizard (Eremias multiocellata). Simultaneously, long-term warming significantly increased the antibacterial activity of serum, immune responses (higher expression of intestinal immune-related genes), and the concentration of short-chain fatty acids (thereby intestinal barrier and immunity) in the lizard. Fecal microbiota transplant experiments further revealed that increased diversity of gut microbiota significantly enhanced antibacterial activity and the immune response of lizards. More specifically, the enhanced immunity is likely due to the higher relative abundance of Bacteroides in warming lizards, given that the bacteria of Bacteroides fragilis regulated IFN-&#x3b2; expression to increase the immune response of lizards under a warming climate.<br><br>CONCLUSIONS: Our study suggests that gut microbiota can help ectotherms cope with climate warming by enhancing host immune response, and highlights the importance of long-term studies on host-microbial interactions and their biological impacts.}, }
@article {pmid38382594, year = {2025}, author = {Wu, JJ and Zheng, X and Wu, C and Ma, W and Wang, Y and Wang, J and Wei, Y and Zeng, X and Zhang, S and Guan, W and Chen, F}, title = {Melatonin alleviates high temperature exposure induced fetal growth restriction via the gut-placenta-fetus axis in pregnant mice.}, journal = {Journal of advanced research}, volume = {68}, number = {}, pages = {131-146}, pmid = {38382594}, issn = {2090-1224}, mesh = {Animals ; *Melatonin/pharmacology ; Female ; Pregnancy ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Fetal Growth Retardation/etiology/prevention &amp; control/drug therapy/metabolism ; *Placenta/drug effects/metabolism ; Fecal Microbiota Transplantation ; Hot Temperature/adverse effects ; Fetus/drug effects ; Lipopolysaccharides ; }, abstract = {INTRODUCTION: Global warming augments the risk of adverse pregnancy outcomes in vulnerable expectant mothers. Pioneering investigations into heat stress (HS) have predominantly centered on its direct impact on reproductive functions, while the potential roles of gut microbiota, despite its significant influence on distant tissues, remain largely unexplored. Our understanding of deleterious mechanisms of HS and the development of effective intervention strategies to mitigate the detrimental impacts are still limited.<br><br>OBJECTIVES: In this study, we aimed to explore the mechanisms by which melatonin targets gut microbes to alleviate HS-induced reproductive impairment.<br><br>METHODS: We firstly evaluated the alleviating effects of melatonin supplementation on HS-induced reproductive disorder in pregnant mice. Microbial elimination and fecal microbiota transplantation (FMT) experiments were then conducted to confirm the efficacy of melatonin through regulating gut microbiota. Finally, a lipopolysaccharide (LPS)-challenged experiment was performed to verify the mechanism by which melatonin alleviates HS-induced reproductive impairment.<br><br>RESULTS: Melatonin supplementation reinstated gut microbiota in heat stressed pregnant mice, reducing LPS-producing bacteria (Aliivibrio) and increasing beneficial butyrate-producing microflora (Butyricimonas). This restoration corresponded to decreased LPS along the maternal gut-placenta-fetus axis, accompanied by enhanced intestinal and placental barrier integrity, safeguarding fetuses from oxidative stress and inflammation, and ultimately improving fetal weight. Further pseudo-sterile and fecal microbiota transplantation trials confirmed that the protective effect of melatonin on fetal intrauterine growth under HS was partially dependent on gut microbiota. In LPS-challenged pregnant mice, melatonin administration mitigated placental barrier injury and abnormal angiogenesis via the inactivation of the TLR4/MAPK/VEGF signaling pathway, ultimately leading to enhanced nutrient transportation in the placenta and thereby improving the fetal weight.<br><br>CONCLUSION: Melatonin alleviates HS-induced low fetal weight during pregnancy via the gut-placenta-fetus axis, the first time highlighting the gut microbiota as a novel intervention target to mitigate the detrimental impact of global temperature rise on vulnerable populations.}, }
@article {pmid38380023, year = {2024}, author = {Chen, L and Xie, L and Tan, J and Li, N and Luo, Y and Li, M and Zhang, S and Wang, Z}, title = {The gut microbiota regulates the depressive-type behaviors and inflammatory processes after severe burn injuries in mice.}, journal = {Heliyon}, volume = {10}, number = {4}, pages = {e25617}, pmid = {38380023}, issn = {2405-8440}, abstract = {An emerging number of studies have recently revealed the correlation between burn injuries and psychological disorders. Gut microbiota and inflammatory factors may play a vital role in this process. Nevertheless, there are few studies conducted to disclose the potential mechanism of the gut microbiota between depression and burn injuries. In this study, we constructed a burn model of C57BL/6 mice, which showed that the symptom of depression became more and more severe with the burn of mice lasted longer. Meanwhile, there are significant differences of composition of gut microbiota among mice before and after burn. Then, we tested the inflammatory factors in the brain and peripheral blood, which showed an increased expression of Iba1, VWF, TNF-α and IL-6, and a decreased expression of IL-10 in burn mice. In addition, the expression of zonula occludens-1 (ZO-1) in cecum showed a down-regulation in burn mice, which indicated impaired intestinal barrier function. Lastly, the crossing fecal microbiota transplantation (FMT) and cohousing experiment were conducted to determine the functions of cross-transplantation of fecal microbiota on the depressive-type behaviours in burned mice. According to the score of Tail suspension test (TST), the burn mice were divided into two groups: Resilient mice (no-depressed mice) and Abnormal mice (depressed mice). After abnormal mice were transplanted with fecal microbiota of resilient mice, the symptom of depression was improved, and the expression of TNF-α, IL-6 and IL-10 return to normal levels (P < 0.05). On the contrary, after resilient mice were transplanted with fecal microbiota of abnormal mice both the TST scores and inflammatory factor developed depressive-type changes. In conclusion, our study demonstrated the changes of gut microbiota and inflammatory factors in depressed burn mice and non-depressed burn mice. The gut microbiota dysbiosis could impaired intestinal barrier function and lead to neuroinflammation, and this phenomenon could be significantly mitigated by FMT.}, }
@article {pmid38378622, year = {2024}, author = {Hao, W and Ma, Q and Wang, L and Yuan, N and Gan, H and He, L and Li, X and Huang, J and Chen, J}, title = {Gut dysbiosis induces the development of depression-like behavior through abnormal synapse pruning in microglia-mediated by complement C3.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {34}, pmid = {38378622}, issn = {2049-2618}, support = {2023M741396//China Postdoctoral Science Foundation/ ; 2021A1515010869; 2022A1515011699//the Guangdong Basic and Applied Basic Research Foundation/ ; 2021A1515010869; 2022A1515011699//the Guangdong Basic and Applied Basic Research Foundation/ ; 82074300, 82174278//National Natural Science Foundation of China/ ; 82074300, 82174278//National Natural Science Foundation of China/ ; 2020B1111100001//Key-Area Research and Development Program of Guangdong Province/ ; 2020B1111100001//Key-Area Research and Development Program of Guangdong Province/ ; 2021B1212040007//Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization/ ; 2021B1212040007//Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization/ ; 202201020052//Science and Technology Program of Guangzhou/ ; 202102010014//the Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine/ ; 202102010014//the Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine/ ; 201911//the Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University/ ; }, mesh = {Animals ; Mice ; Complement C3 ; *Depression/microbiology ; Dysbiosis ; *Microglia/physiology ; Synapses/physiology ; }, abstract = {BACKGROUND: Remodeling eubiosis of the gut microenvironment may contribute to preventing the occurrence and development of depression. Mounting experimental evidence has shown that complement C3 signaling is associated with the pathogenesis of depression, and disruption of the gut microbiota may be an underlying cause of complement system activation. However, the mechanism by which complement C3 participates in gut-brain crosstalk in the pathogenesis of depression remains unknown.<br><br>RESULTS: In the present study, we found that chronic unpredictable mild stress (CUMS)-induced mice exhibited obvious depression-like behavior as well as cognitive impairment, which was associated with significant gut dysbiosis, especially enrichment of Proteobacteria and elevation of microbiota-derived lipopolysaccharides (LPS). In addition, peripheral and central complement C3 activation and central C3/CR3-mediated aberrant synaptic pruning in microglia have also been observed. Transplantation of gut microbiota from CUMS-induced depression model mice into specific pathogen-free and germ-free mice induced depression-like behavior and concomitant cognitive impairment in the recipient mice, accompanied by increased activation of the complement C3/CR3 pathway in the prefrontal cortex and abnormalities in microglia-mediated synaptic pruning. Conversely, antidepressants and fecal microbiota transplantation from antidepressant-treated donors improved depression-like behaviors and restored gut microbiome disturbances in depressed mice. Concurrently, inhibition of the complement C3/CR3 pathway, amelioration of abnormal microglia-mediated synaptic pruning, and increased expression of the synapsin and postsynaptic density protein 95 were observed. Collectively, our results revealed that gut dysbiosis induces the development of depression-like behaviors through abnormal synapse pruning in microglia-mediated by complement C3, and the inhibition of abnormal synaptic pruning is the key to targeting microbes to treat depression.<br><br>CONCLUSIONS: Our findings provide novel insights into the involvement of complement C3/CR3 signaling and aberrant synaptic pruning of chemotactic microglia in gut-brain crosstalk in the pathogenesis of depression. Video Abstract.}, }
@article {pmid38376627, year = {2024}, author = {Isali, I and Helstrom, EK and Uzzo, N and Lakshmanan, A and Nandwana, D and Valentine, H and Sindhani, M and Abbosh, P and Bukavina, L}, title = {Current Trends and Challenges of Microbiome Research in Bladder Cancer.}, journal = {Current oncology reports}, volume = {26}, number = {3}, pages = {292-298}, pmid = {38376627}, issn = {1534-6269}, mesh = {Humans ; Mice ; Animals ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Urinary Bladder Neoplasms ; High-Throughput Nucleotide Sequencing/methods ; }, abstract = {PURPOSE OF THE REVIEW: Microbiome research has provided valuable insights into the associations between microbial communities and bladder cancer. However, this field faces significant challenges that hinder the interpretation, generalization, and translation of findings into clinical practice. This review aims to elucidate these challenges and highlight the importance of addressing them for the advancement of microbiome research in bladder cancer.<br><br>RECENT FINDINGS: Recent findings underscore the complexities involved in microbiome research, particularly in the context of bladder cancer. Challenges include low microbial biomass in urine samples, potential contamination issues during collection and processing, variability in sequencing methods and primer selection, and the difficulty of establishing causality between microbiota and bladder cancer. Studies have shown the impact of sample storage conditions and DNA isolation kits on microbiome analysis, emphasizing the need for standardization. Additionally, variations in urine collection methods can introduce contamination and affect results. The choice of 16S rRNA gene amplicon sequencing or shotgun metagenomic sequencing introduces technical challenges, including primer selection and sequencing read length. Establishing causality between the microbiota and bladder cancer requires experimental methods like fecal microbiota transplantation and human microbiota-associated murine models, which face their own set of challenges. Translating microbiome research into therapeutic applications is hindered by methodological variability, incomplete understanding of bioactive molecules, imperfect animal models, and the inherent heterogeneity of microbiome communities among individuals. Microbiome research in bladder cancer presents significant challenges stemming from technical and conceptual complexities. Addressing these challenges through standardization, improved experimental models, and advanced analytical approaches is essential for advancing our understanding of the microbiome's role in bladder cancer and its potential clinical applications. Achieving this goal can lead to improved patient outcomes and novel therapeutic strategies in the future.}, }
@article {pmid38375101, year = {2024}, author = {Monday, L and Tillotson, G and Chopra, T}, title = {Microbiota-Based Live Biotherapeutic Products for Clostridioides Difficile Infection- The Devil is in the Details.}, journal = {Infection and drug resistance}, volume = {17}, number = {}, pages = {623-639}, pmid = {38375101}, issn = {1178-6973}, abstract = {Clostridioides difficile infection (CDI) remains a significant contributor to healthcare costs and morbidity due to high rates of recurrence. Currently, available antibiotic treatment strategies further disrupt the fecal microbiome and do not address the alterations in commensal flora (dysbiosis) that set the stage for CDI. Advances in microbiome-based research have resulted in the development of new agents, classified as live biotherapeutic products (LBPs), for preventing recurrent CDI (rCDI) by restoring eubiosis. Prior to the LBPs, fecal microbiota transplantation (FMT) was available for this purpose; however, lack of large-scale availability and safety concerns have remained barriers to its widespread use. The LBPs are an exciting development, but questions remain. Some are derived directly from human stool while other developmental products contain a defined microbial consortium manufactured ex vivo, and they may be composed of either living bacteria or their spores, making it difficult to compare members of this heterogenous drug class to one another. None have been studied head-to head or against FMT in preventing rCDI. As a class, they have considerable variability in their biologic composition, biopharmaceutic science, route of administration, stages of development, and clinical trial data. This review will start by explaining the role of dysbiosis in CDI, then give the details of the biopharmaceutical components for the LBPs which are approved or in development including how they differ from FMT and from one another. We then discuss the clinical trials of the LBPs currently approved for rCDI and end with the future clinical directions of LBPs beyond C. difficile.}, }
@article {pmid38370838, year = {2024}, author = {McMillan, AS and Zhang, G and Dougherty, MK and McGill, SK and Gulati, AS and Baker, ES and Theriot, CM}, title = {Metagenomic, metabolomic, and lipidomic shifts associated with fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.02.07.579219}, pmid = {38370838}, issn = {2692-8205}, support = {T32 GM133366/GM/NIGMS NIH HHS/United States ; }, abstract = {Recurrent C. difficile infection (rCDI) is an urgent public health threat for which the last resort and lifesaving treatment is a fecal microbiota transplant (FMT). However, the exact mechanisms which mediate a successful FMT are not well understood. Here we use longitudinal stool samples collected from patients undergoing FMT to evaluate changes in the microbiome, metabolome, and lipidome after successful FMTs. We show changes in the abundance of many lipids, specifically acylcarnitines and bile acids, in response to FMT. These changes correlate with Enterobacteriaceae, which encode carnitine metabolism genes, and Lachnospiraceae, which encode bile salt hydrolases and baiA genes. LC-IMS-MS revealed a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here we define the structural and functional changes in successful FMTs. This information will help guide targeted Live Biotherapeutic Product development for the treatment of rCDI and other intestinal diseases.}, }
@article {pmid38369241, year = {2025}, author = {Meroni, M and Longo, M and Paolini, E and Dongiovanni, P}, title = {A narrative review about cognitive impairment in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Another matter to face through a holistic approach.}, journal = {Journal of advanced research}, volume = {68}, number = {}, pages = {231-240}, pmid = {38369241}, issn = {2090-1224}, mesh = {Humans ; *Cognitive Dysfunction/etiology/therapy ; *Fatty Liver/complications/psychology ; *Metabolic Syndrome/complications ; Holistic Health ; Quality of Life ; }, abstract = {BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic hepatic disorder worldwide in both adults and children. It is well established that MASLD represents the hepatic manifestation of the metabolic syndrome whose definition includes the presence of obesity, type 2 diabetes (T2D), dyslipidemia, hypertension and hypercoagulability. All these conditions contribute to a chronic inflammatory status which may impact on blood brain barrier (BBB) integrity leading to an impaired function of central nervous system (CNS).<br><br>AIM OF REVIEW: Since the mechanisms underlying the brain-liver-gut axis derangement are still inconclusive, the present narrative review aims to make a roundup of the most recent studies regarding the cognitive decline in MASLD also highlighting possible therapeutic strategies to reach a holistic advantage for the patients.<br><br>Due to its ever-growing prevalence, the MASLD-related mental dysfunction represents an enormous socio-economic burden since it largely impacts on the quality of life of patients as well as on their working productivity. Indeed, cognitive decline in MASLD translates in low concentration and processing speed, reduced memory, sleepiness but also anxiety and depression. Chronic systemic inflammation, hyperammonemia, genetic background and intestinal dysbiosis possibly contribute to the cognitive decline in MASLD patients. However, its diagnosis is still underestimated since the leading mechanisms are multi-faceted and unexplained and do not exist standardized diagnostic tools or cognitive test strategies. In this scenario, nutritional and lifestyle interventions as well as intestinal microbiota manipulation (probiotics, fecal transplantation) may represent new approaches to counteract mental impairment in these subjects. In sum, to face the "mental aspect" of this multifactorial disease which is almost unexplored, cognitive tools should be introduced in the management of MASLD patients.}, }
@article {pmid38367807, year = {2024}, author = {Xu, H and Li, O and Kim, D and Yang, F and Bao, Z}, title = {Age-Related Gut Microbiota Transplantation Disrupts Myocardial Energy Homeostasis and Induces Oxidative Damage.}, journal = {The Journal of nutrition}, volume = {154}, number = {4}, pages = {1189-1199}, doi = {10.1016/j.tjnut.2024.02.011}, pmid = {38367807}, issn = {1541-6100}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/analysis ; Glucose/metabolism ; Cardiomegaly ; Homeostasis ; Oxidative Stress ; }, abstract = {BACKGROUND: Aging-related energy homeostasis significantly affects normal heart function and disease development. The relationship between the gut microbiota and host energy metabolism has been well established. However, the influence of an aged microbiota on energy metabolism in the heart remains unclear.<br><br>OBJECTIVE: The objective of this was to explore the effects of age-related microbiota composition on energy metabolism in the heart.<br><br>METHODS: In this study, we used the fecal microbiota transplantation (FMT) method. The fecal microbiota from young (2-3 mo) and aged (18-22 mo) donor mice were transplanted into separate groups of young (2-3 mo) recipient mice. The analysis utilized whole 16S rRNA sequencing and plasma metabolomics to assess changes in the gut microbiota composition and metabolic potential. Energy changes were monitored by performing an oral glucose tolerance test, biochemical testing, body composition analysis, and metabolic cage measurements. Metabolic markers and markers of DNA damage were assessed in heart samples.<br><br>RESULTS: FMT of an aged microbiota changed the composition of the recipient's gut microbiota, leading to an elevated Firmicutes-to-Bacteroidetes ratio. It also affected overall energy metabolism, resulting in elevated plasma glucose concentrations, impaired glucose tolerance, and epididymal fat accumulation. Notably, FMT of an aged microbiota increased the heart weight and promoted cardiac hypertrophy. Furthermore, there were significant associations between heart weight and cardiac hypertrophy indicators, epididymal fat weight, and fasting glucose concentrations. Mechanistically, FMT of an aged microbiota modulated the glucose metabolic pathway and induced myocardial oxidative damage.<br><br>CONCLUSIONS: Our findings suggested that an aged microbiota can modulate metabolism and induce cardiac injury. This highlights the possible role of the gut microbiota in age-related metabolic disorders and cardiac dysfunction.}, }
@article {pmid38367621, year = {2024}, author = {Chen, Q and Wu, C and Xu, J and Ye, C and Chen, X and Tian, H and Zong, N and Zhang, S and Li, L and Gao, Y and Zhao, D and Lv, X and Yang, Q and Wang, L and Cui, J and Lin, Z and Lu, J and Yang, R and Yin, F and Qin, N and Li, N and Xu, Q and Qin, H}, title = {Donor-recipient intermicrobial interactions impact transfer of subspecies and fecal microbiota transplantation outcome.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {3}, pages = {349-365.e4}, doi = {10.1016/j.chom.2024.01.013}, pmid = {38367621}, issn = {1934-6069}, mesh = {Feces ; *Autism Spectrum Disorder ; East Asian People ; Humans ; Gastrointestinal Tract ; *Gastrointestinal Microbiome/genetics ; Treatment Outcome ; Clostridium Infections ; Fecal Microbiota Transplantation ; }, abstract = {Studies on fecal microbiota transplantation (FMT) have reported inconsistent connections between clinical outcomes and donor strain engraftment. Analyses of subspecies-level crosstalk and its influences on lineage transfer in metagenomic FMT datasets have proved challenging, as single-nucleotide polymorphisms (SNPs) are generally not linked and are often absent. Here, we utilized species genome bin (SGB), which employs co-abundance binning, to investigate subspecies-level microbiome dynamics in patients with autism spectrum disorder (ASD) who had gastrointestinal comorbidities and underwent encapsulated FMT (Chinese Clinical Trial: 2100043906). We found that interactions between donor and recipient microbes, which were overwhelmingly phylogenetically divergent, were important for subspecies transfer and positive clinical outcomes. Additionally, a donor-recipient SGB match was indicative of a high likelihood of strain transfer. Importantly, these ecodynamics were shared across FMT datasets encompassing multiple diseases. Collectively, these findings provide detailed insight into specific microbial interactions and dynamics that determine FMT success.}, }
@article {pmid38367140, year = {2024}, author = {Tao, Y and Luo, CJ and Zhang, BH and Shen, XY and Zhao, RK and Ma, BY and Shen, N and Luo, CY and Wang, JM and Xia, YJ and Xie, L and Chen, J and Mo, X}, title = {Diagnostic performance of a multiplexed gastrointestinal PCR panel for identifying diarrheal pathogens in children undergoing hematopoietic stem cell transplant.}, journal = {World journal of pediatrics : WJP}, volume = {20}, number = {9}, pages = {966-975}, pmid = {38367140}, issn = {1867-0687}, support = {20dz2260900//Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics/ ; 20dz2261100//Shanghai Key Laboratory of Emergency Prevention Diagnosis and Treatment of Respiratory Infectious Diseases/ ; 22ZR1440300//Natural Science Foundation of Shanghai/ ; 81971890//National Natural Science Foundation of China/ ; PKJ2020-Y01//Science and Technology Innovation Plan Of Shanghai Science and Technology CommissionScience and Technology Development Fund of Shanghai Pudong New Area/ ; 20Y11903600//Scientific and Technology Commission of Shanghai Municipality/ ; 2022XD054//Shanghai Municipal Health Commission/ ; 22SG13//Shanghai Municipal Education Commission/ ; }, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; *Diarrhea/microbiology/diagnosis/etiology ; Child ; Child, Preschool ; Prospective Studies ; Adolescent ; Multiplex Polymerase Chain Reaction ; Feces/microbiology/virology ; Infant ; Graft vs Host Disease/diagnosis ; }, abstract = {BACKGROUND: Diarrhea is a common complication of hematopoietic stem cell transplantation (HSCT) and is associated with substantial morbidity, but its etiology is often unknown. Etiologies of diarrhea in this population include infectious causes, chemotherapy- or medication-induced mucosal injury and graft-versus-host disease (GVHD). Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial, and the etiologies often overlap in transplant patients. The objectives of this study were to evaluate whether the FilmArray gastrointestinal (GI) panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation infection.<br><br>METHODS: From November 2019 to February 2021, a total of 158 patients undergoing HSCT were prospectively included in the study. Stool specimens were obtained from all HSCT recipients prior to conditioning therapy, 28&#x2009;&#xb1;&#x2009;7&#xa0;days after transplantation and at any new episode of diarrhea. All stool samples were tested by the FilmArray GI panel and other clinical microbiological assays.<br><br>RESULTS: The primary cause of post-transplantation diarrhea was infection (57/84, 67.86%), followed by medication (38/84, 45.24%) and GVHD (21/84, 25.00%). Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy, and the incidence of infectious diarrhea was significantly higher in colonized patients (47/95, 49.47%) than in non-colonized patients (10/63, 15.87%) (P&#x2009;<&#x2009;0.001). Fourteen of 19 (73.68%) patients who were initially colonized with norovirus pre-transplantation developed a post-transplantation norovirus infection. Twenty-four of 62 (38.71%) patients colonized with Clostridium difficile developed a diarrheal infection. In addition, FilmArray GI panel testing improved the diagnostic yield by almost twofold in our study (55/92, 59.78% vs. 30/92, 32.61%).<br><br>CONCLUSIONS: Our data show that more than half of pediatric patients who were admitted for HSCT were colonized with various gastrointestinal pathogens, and more than one-third of these pathogens were associated with post-transplantation diarrhea. In addition, the FilmArray GI panel can increase the detection rate of diarrheal pathogens in pediatric HSCT patients, but the panel needs to be optimized for pathogen species, and further studies assessing its clinical impact and cost-effectiveness in this specific patient population are also needed.}, }
@article {pmid38365257, year = {2024}, author = {Dong, Q and Hua, D and Wang, X and Jiao, Y and Liu, L and Deng, Q and Wu, T and Zou, H and Zhao, C and Wang, C and Reng, J and Ding, L and Hu, S and Shi, J and Wang, Y and Zhang, H and Sheng, Y and Sun, W and Shen, Y and Tang, L and Kong, X and Chen, L}, title = {Temporal colonization and metabolic regulation of the gut microbiome in neonatal oxen at single nucleotide resolution.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {38365257}, issn = {1751-7370}, support = {32394052//National Natural Science Foundation of China/ ; JSSCBS20221815//Jiangsu Shuangchuang Project/ ; BK20220709//Natural Science Foundation of Jiangsu/ ; C2022204247//Natural Science Foundation of Hebei/ ; CMCM202204//Nanjing Medical University/ ; //Development of Jiangsu Higher Education Institutions Priority Academic Program/ ; }, mesh = {Infant, Newborn ; Humans ; Female ; *Gastrointestinal Microbiome/physiology ; Nucleotides ; Levodopa ; *Microbiota ; Feces ; Metagenomics/methods ; }, abstract = {The colonization of microbes in the gut is key to establishing a healthy host-microbiome symbiosis for newborns. We longitudinally profiled the gut microbiome in a model consisting of 36 neonatal oxen from birth up to 2 months postpartum and carried out microbial transplantation to reshape their gut microbiome. Genomic reconstruction of deeply sequenced fecal samples resulted in a total of 3931 metagenomic-assembled genomes from 472 representative species, of which 184 were identified as new species when compared with existing databases of oxen. Single nucleotide level metagenomic profiling shows a rapid influx of microbes after birth, followed by dynamic shifts during the first few weeks of life. Microbial transplantation was found to reshape the genetic makeup of 33 metagenomic-assembled genomes (FDR < 0.05), mainly from Prevotella and Bacteroides species. We further linked over 20 million microbial single nucleotide variations to 736 plasma metabolites, which enabled us to characterize 24 study-wide significant associations (P < 4.4 × 10-9) that identify the potential microbial genetic regulation of host immune and neuro-related metabolites, including glutathione and L-dopa. Our integration analyses further revealed that microbial genetic variations may influence the health status and growth performance by modulating metabolites via structural regulation of their encoded proteins. For instance, we found that the albumin levels and total antioxidant capacity were correlated with L-dopa, which was determined by single nucleotide variations via structural regulations of metabolic enzymes. The current results indicate that temporal colonization and transplantation-driven strain replacement are crucial for newborn gut development, offering insights for enhancing newborn health and growth.}, }
@article {pmid38363696, year = {2024}, author = {Weber, AT and Lichtenstein, GR}, title = {Evidence-Based Approach to Chronic Antibiotic Refractory Pouchitis: A Review.}, journal = {Diseases of the colon and rectum}, volume = {67}, number = {S1}, pages = {S99-S105}, doi = {10.1097/DCR.0000000000003207}, pmid = {38363696}, issn = {1530-0358}, mesh = {*Pouchitis/drug therapy/therapy ; Humans ; *Anti-Bacterial Agents/therapeutic use ; *Proctocolectomy, Restorative/adverse effects/methods ; Chronic Disease ; Fecal Microbiota Transplantation/methods ; Evidence-Based Medicine ; }, abstract = {BACKGROUND: Chronic antibiotic refractory pouchitis after restorative proctocolectomy with IPAA, characterized by at least 4 weeks of pouchitis symptoms that have not responded to standard antibiotic therapy, presents a therapeutic challenge for patients and health care providers.<br><br>OBJECTIVE: The aim of this narrative review was to summarize the current evidence regarding the management of chronic antibiotic refractory pouchitis.<br><br>DATA SOURCES: Studies were identified through a search of the PubMed database from the National Library of Medicine.<br><br>STUDY SELECTION: We included case series, cohort studies, randomized controlled trials, and systematic reviews with meta-analyses that addressed chronic antibiotic refractory pouchitis management, with prioritization of data published within the past 3 to 5 years.<br><br>INTERVENTION: Studies examining pharmacologic and select nonpharmacologic interventions were included.<br><br>MAIN OUTCOME MEASURE: Outcomes measures included clinical, endoscopic, and histologic end points.<br><br>RESULTS: Mesalamine has demonstrated efficacy in symptom improvement but no improvement in quality of life. Budesonide has demonstrated high rates of clinical remission that have mostly been sustained in a small number of patients. Anti-tumor necrosis factor therapies have demonstrated efficacy in reaching clinical and even endoscopic end points, although rates of treatment discontinuation were not insignificant. Limited evidence is encouraging for the use of ustekinumab in achieving clinical response. Data for vedolizumab are favorable across clinical, endoscopic, and histologic end points, including one of the only randomized, placebo-controlled trials. Nonmedication therapies, including hyperbaric oxygen therapy and fecal microbiota transplant, have undergone limited evaluation, and concerns about the ultimate accessibility of these therapies remain.<br><br>LIMITATIONS: Overall, studies assessing therapeutic options for chronic antibiotic refractory pouchitis are mostly limited to case series and retrospective studies with small sample sizes.<br><br>CONCLUSIONS: Biologic therapies have demonstrated efficacy in the management of chronic antibiotic refractory pouchitis and offer a steroid-sparing option for refractory disease. Nonpharmacologic therapies, including hyperbaric oxygen and fecal microbiota transplant, require further exploration. See video from symposium .}, }
@article {pmid38362864, year = {2024}, author = {Schöler, D and Schnabl, B}, title = {The role of the microbiome in liver disease.}, journal = {Current opinion in gastroenterology}, volume = {40}, number = {3}, pages = {134-142}, pmid = {38362864}, issn = {1531-7056}, support = {R01 AA020703/AA/NIAAA NIH HHS/United States ; I01 BX004594/BX/BLRD VA/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; U01 AA026939/AA/NIAAA NIH HHS/United States ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy ; *Liver Neoplasms/therapy ; *Liver Diseases, Alcoholic/drug therapy ; *Probiotics/therapeutic use ; *Gastrointestinal Microbiome/physiology ; *Hepatitis, Alcoholic ; }, abstract = {PURPOSE OF REVIEW: The intestinal microbiome and the gut-liver axis play a major role in health and disease. The human gut harbors trillions of microbes and a disruption of the gut homeostasis can contribute to liver disease. In this review, the progress in the field within the last 3 years is summarized, focusing on metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), autoimmune liver disease (AILD), and hepatocellular carcinoma (HCC).<br><br>RECENT FINDINGS: Changes in the fecal virome and fungal mycobiome have been described in patients with various liver diseases. Several microbial derived metabolites including endogenous ethanol produced by bacteria, have been mechanistically linked to liver disease such as MASLD. Virulence factors encoded by gut bacteria contribute to ALD, AILD and HCC. Novel therapeutic approaches focused on the microbiome including phages, pre- and postbiotics have been successfully used in preclinical models. Fecal microbiota transplantation has been effective in attenuating liver disease. Probiotics are safe in patients with alcohol-associated hepatitis and improve liver disease and alcohol addiction.<br><br>SUMMARY: The gut-liver axis plays a key role in the pathophysiology of liver diseases. Understanding the microbiota in liver disease can help to develop precise microbiota centered therapies.}, }
@article {pmid38361239, year = {2024}, author = {Mohamed, ME and Saqr, A and Staley, C and Onyeaghala, G and Teigen, L and Dorr, CR and Remmel, RP and Guan, W and Oetting, WS and Matas, AJ and Israni, AK and Jacobson, PA}, title = {Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation.}, journal = {Transplantation}, volume = {108}, number = {9}, pages = {1895-1910}, pmid = {38361239}, issn = {1534-6080}, support = {R01 AI140303/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Immunosuppressive Agents/pharmacokinetics/adverse effects ; *Gastrointestinal Microbiome/drug effects ; *Organ Transplantation/adverse effects ; Graft Rejection/prevention &amp; control/immunology/microbiology ; Animals ; }, abstract = {The human microbiome is associated with human health and disease. Exogenous compounds, including pharmaceutical products, are also known to be affected by the microbiome, and this discovery has led to the field of pharmacomicobiomics. The microbiome can also alter drug pharmacokinetics and pharmacodynamics, possibly resulting in side effects, toxicities, and unanticipated disease response. Microbiome-mediated effects are referred to as drug-microbiome interactions (DMI). Rapid advances in the field of pharmacomicrobiomics have been driven by the availability of efficient bacterial genome sequencing methods and new computational and bioinformatics tools. The success of fecal microbiota transplantation for recurrent Clostridioides difficile has fueled enthusiasm and research in the field. This review focuses on the pharmacomicrobiome in transplantation. Alterations in the microbiome in transplant recipients are well documented, largely because of prophylactic antibiotic use, and the potential for DMI is high. There is evidence that the gut microbiome may alter the pharmacokinetic disposition of tacrolimus and result in microbiome-specific tacrolimus metabolites. The gut microbiome also impacts the enterohepatic recirculation of mycophenolate, resulting in substantial changes in pharmacokinetic disposition and systemic exposure. The mechanisms of these DMI and the specific bacteria or communities of bacteria are under investigation. There are little or no human DMI data for cyclosporine A, corticosteroids, and sirolimus. The available evidence in transplantation is limited and driven by small studies of heterogeneous designs. Larger clinical studies are needed, but the potential for future clinical application of the pharmacomicrobiome in avoiding poor outcomes is high.}, }
@article {pmid38360862, year = {2024}, author = {Loh, JS and Mak, WQ and Tan, LKS and Ng, CX and Chan, HH and Yeow, SH and Foo, JB and Ong, YS and How, CW and Khaw, KY}, title = {Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases.}, journal = {Signal transduction and targeted therapy}, volume = {9}, number = {1}, pages = {37}, pmid = {38360862}, issn = {2059-3635}, mesh = {Humans ; Brain/metabolism ; *Neurodegenerative Diseases/therapy/metabolism ; Brain-Gut Axis ; *Probiotics/therapeutic use ; Prebiotics ; }, abstract = {The human gastrointestinal tract is populated with a diverse microbial community. The vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect of human biology, including health maintenance, development, aging, and disease. The advent of new sequencing technologies and culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations to shed light on microbiome-host interactions. Evidence has unveiled the bidirectional communication between the gut microbiome and the central nervous system, referred to as the "microbiota-gut-brain axis". The microbiota-gut-brain axis represents an important regulator of glial functions, making it an actionable target to ameliorate the development and progression of neurodegenerative diseases. In this review, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases. As the gut microbiome provides essential cues to microglia, astrocytes, and oligodendrocytes, we examine the communications between gut microbiota and these glial cells during healthy states and neurodegenerative diseases. Subsequently, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases using a metabolite-centric approach, while also examining the role of gut microbiota-related neurotransmitters and gut hormones. Next, we examine the potential of targeting the intestinal barrier, blood-brain barrier, meninges, and peripheral immune system to counteract glial dysfunction in neurodegeneration. Finally, we conclude by assessing the pre-clinical and clinical evidence of probiotics, prebiotics, and fecal microbiota transplantation in neurodegenerative diseases. A thorough comprehension of the microbiota-gut-brain axis will foster the development of effective therapeutic interventions for the management of neurodegenerative diseases.}, }
@article {pmid38357521, year = {2024}, author = {Kriz, J and Hysperska, V and Bebrova, E and Roznetinska, M}, title = {Faecal microbiota transplantation for multidrug-resistant organism decolonization in spinal cord injury patients: a case series.}, journal = {Infection prevention in practice}, volume = {6}, number = {1}, pages = {100340}, pmid = {38357521}, issn = {2590-0889}, abstract = {INTRODUCTION: The increase of multidrug-resistant (MDR) bacteria in healthcare settings is a worldwide concern. Isolation precautions must be implemented to control the significant risk of transmitting these pathogens among patients. Antibiotic decolonization is not recommended because of the threat of increasing antibiotic resistance. However, restoring gut microflora through faecal microbiota transplantation (FMT) is a hopeful solution.<br><br>PATIENTS AND METHOD: In 2019-2022, FMT was indicated in seven patients of the Spinal Cord Unit at University Hospital Motol who were colonized with MDR bacterial strains. Five patients tested positive for carriage of carbapenemase-producing Enterobacteriaceae, and two were carriers of vancomycin-resistant enterococci. Isolation measures were implemented in all patients. Donor faeces were obtained from healthy, young, screened volunteers. According to local protocol, 200-300 ml of suspension was applied through a nasoduodenal tube.<br><br>RESULTS: The mean age of the patients was 43 years. The mean length of previous hospital stay was 93.2 days. All patients were treated with broad-spectrum antibiotics for infectious complications before detecting colonisation with MDR bacteria. MDR organism decolonization was achieved in five patients, and consequently, isolation measures could be removed. Colonization persisted in two patients, one of whom remained colonized even after a third FMT. No adverse events were reported after FMT.<br><br>CONCLUSION: FMT is a safe and effective strategy to eradicate MDR bacteria, even in spinal cord injured patients. FMT can allow relaxation of isolation facilitates, the participation of patients in a complete rehabilitation program, their social integration, and transfer to follow-up rehabilitation centres.}, }
@article {pmid38357210, year = {2023}, author = {Zhang, H and Dong, M and Zheng, J and Yang, Y and He, J and Liu, T and Wei, H}, title = {Fecal bacteria-free filtrate transplantation is proved as an effective way for the recovery of radiation-induced individuals in mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1343752}, pmid = {38357210}, issn = {2235-2988}, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation/methods ; Dysbiosis/therapy/microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Microbiota ; }, abstract = {BACKGROUND: Ionizing radiation can cause intestinal microecological dysbiosis, resulting in changes in the composition and function of gut microbiota. Altered gut microbiota is closely related to the development and progression of radiation-induced intestinal damage. Although microbiota-oriented therapeutic options such as fecal microbiota transplantation (FMT) have shown some efficacy in treating radiation toxicity, safety concerns endure. Therefore, fecal bacteria-free filtrate transplantation (FFT), which has the potential to become a possible alternative therapy, is well worth investigating. Herein, we performed FFT in a mouse model of radiation exposure and monitored its effects on radiation damage phenotypes, gut microbiota, and metabolomic profiles to assess the effectiveness of FFT as an alternative therapy to FMT safety concerns.<br><br>RESULTS: FFT treatment conferred radioprotection against radiation-induced toxicity, representing as better intestinal integrity, robust proinflammatory and anti-inflammatory cytokines homeostasis, and accompanied by significant shifts in gut microbiome. The bacterial compartment of recipients following FFT was characterized by an enrichment of radioprotective microorganisms (members of family Lachnospiraceae). Furthermore, metabolome data revealed increased levels of microbially generated short-chain fatty acids (SCFAs) in the feces of FFT mice.<br><br>CONCLUSIONS: FFT improves radiation-induced intestinal microecological dysbiosis by reshaping intestinal mucosal barrier function, gut microbiota configurations, and host metabolic profiles, highlighting FFT regimen as a promising safe alternative therapy for FMT is effective in the treatment of radiation intestinal injury.}, }
@article {pmid38356049, year = {2024}, author = {van Bergeijk, DA and Augustijn, HE and Elsayed, SS and Willemse, J and Carrión, VJ and Du, C and Urem, M and Grigoreva, LV and Cheprasov, MY and Grigoriev, S and Jansen, H and Wintermans, B and Budding, AE and Spaink, HP and Medema, MH and van Wezel, GP}, title = {Taxonomic and metabolic diversity of Actinomycetota isolated from faeces of a 28,000-year-old mammoth.}, journal = {Environmental microbiology}, volume = {26}, number = {2}, pages = {e16589}, doi = {10.1111/1462-2920.16589}, pmid = {38356049}, issn = {1462-2920}, support = {//Universiteit Leiden/ ; 101055020-COMMUNITY//European Research Council/International ; 948770-DECIPHER//European Research Council/International ; }, mesh = {Animals ; Phylogeny ; *Mammoths ; Genomics ; *Streptomyces/genetics ; *Actinomycetales ; Feces ; }, abstract = {Ancient environmental samples, including permafrost soils and frozen animal remains, represent an archive with microbial communities that have barely been explored. This yet unexplored microbial world is a genetic resource that may provide us with new evolutionary insights into recent genomic changes, as well as novel metabolic pathways and chemistry. Here, we describe Actinomycetota Micromonospora, Oerskovia, Saccharopolyspora, Sanguibacter and Streptomyces species were successfully revived and their genome sequences resolved. Surprisingly, the genomes of these bacteria from an ancient source show a large phylogenetic distance to known strains and harbour many novel biosynthetic gene clusters that may well represent uncharacterised biosynthetic potential. Metabolic profiles of the strains display the production of known molecules like antimycin, conglobatin and macrotetrolides, but the majority of the mass features could not be dereplicated. Our work provides insights into Actinomycetota isolated from an ancient source, yielding unexplored genomic information that is not yet present in current databases.}, }
@article {pmid38355755, year = {2024}, author = {Zhang, J and Hasty, J and Zarrinpar, A}, title = {Live bacterial therapeutics for detection and treatment of colorectal cancer.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {21}, number = {5}, pages = {295-296}, pmid = {38355755}, issn = {1759-5053}, support = {R01 EB030134/EB/NIBIB NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; R01 AI163483/AI/NIAID NIH HHS/United States ; U01 CA265719/CA/NCI NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; }, mesh = {*Colorectal Neoplasms/diagnosis/therapy ; Humans ; Probiotics/therapeutic use ; Gastrointestinal Microbiome ; }, abstract = {Live microorganisms can be manipulated and engineered for colorectal cancer detection and treatment through methods such as faecal microbiota transplantation, native bacteria engineering and synthetic circuit engineering. Although promising, substantial effort is required to translate these approaches for clinical use.}, }
@article {pmid38353638, year = {2024}, author = {Liu, B and Fan, L and Wang, Y and Wang, H and Yan, Y and Chen, S and Hung, I and Liu, C and Wei, H and Ge, L and Ren, W}, title = {Gut microbiota regulates host melatonin production through epithelial cell MyD88.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2313769}, pmid = {38353638}, issn = {1949-0984}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Escherichia coli ; *Melatonin ; Myeloid Differentiation Factor 88/genetics ; Adaptor Proteins, Signal Transducing ; Epithelial Cells ; }, abstract = {Melatonin has various physiological effects, such as the maintenance of circadian rhythms, anti-inflammatory functions, and regulation of intestinal barriers. The regulatory functions of melatonin in gut microbiota remodeling have also been well clarified; however, the role of gut microbiota in regulating host melatonin production remains poorly understood. To address this, we studied the contribution of gut microbiota to host melatonin production using gut microbiota-perturbed models. We demonstrated that antibiotic-treated and germ-free mice possessed diminished melatonin levels in the serum and elevated melatonin levels in the colon. The influence of the intestinal microbiota on host melatonin production was further confirmed by fecal microbiota transplantation. Notably, Lactobacillus reuteri (L. R) and Escherichia coli (E. coli) recapitulated the effects of gut microbiota on host melatonin production. Mechanistically, L. R and E. coli activated the TLR2/4/MyD88/NF-κB signaling pathway to promote expression of arylalkylamine N-acetyltransferase (AANAT, a rate-limiting enzyme for melatonin production), and MyD88 deficiency in colonic epithelial cells abolished the influence of intestinal microbiota on colonic melatonin production. Collectively, we revealed a specific underlying mechanism of gut microbiota to modulate host melatonin production, which might provide novel therapeutic ideas for melatonin-related diseases.}, }
@article {pmid38352546, year = {2024}, author = {Kellogg, TD and Ceglia, S and Mortzfeld, BM and Zeamer, AL and Foley, SE and Ward, DV and Bhattarai, SK and McCormick, BA and Reboldi, A and Bucci, V}, title = {Microbiota encoded fatty-acid metabolism expands tuft cells to protect tissues homeostasis during Clostridioides difficile infection in the large intestine.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38352546}, issn = {2692-8205}, support = {T32 AI007349/AI/NIAID NIH HHS/United States ; U01 AI172987/AI/NIAID NIH HHS/United States ; }, abstract = {Metabolic byproducts of the intestinal microbiota are crucial in maintaining host immune tone and shaping inter-species ecological dynamics. Among these metabolites, succinate is a driver of tuft cell (TC) differentiation and consequent type 2 immunity-dependent protection against invading parasites in the small intestine. Succinate is also a growth enhancer of the nosocomial pathogen Clostridioides difficile in the large intestine. To date, no research has shown the role of succinate in modulating TC dynamics in the large intestine, or the relevance of this immune pathway to C. difficile pathophysiology. Here we reveal the existence of a three-way circuit between commensal microbes, C. difficile and host epithelial cells which centers around succinate. Through selective microbiota depletion experiments we demonstrate higher levels of type 2 cytokines leading to expansion of TCs in the colon. We then demonstrate the causal role of the microbiome in modulating colonic TC abundance and subsequent type 2 cytokine induction using rational supplementation experiments with fecal transplants and microbial consortia of succinate-producing bacteria. We show that administration of a succinate-deficient Bacteroides thetaiotaomicron knockout (Δfrd) significantly reduces the enhanced type 2 immunity in mono-colonized mice. Finally, we demonstrate that mice prophylactically administered with the consortium of succinate-producing bacteria show reduced C. difficile-induced morbidity and mortality compared to mice administered with heat-killed bacteria or the vehicle. This effect is reduced in a partial tuft cell knockout mouse, Pou2f3[+/-], and nullified in the tuft cell knockout mouse, Pou2f3[-/-], confirming that the observed protection occurs via the TC pathway. Succinate is an intermediary metabolite of the production of short-chain fatty acids, and its concentration often increases during dysbiosis. The first barrier to enteric pathogens alike is the intestinal epithelial barrier, and host maintenance and strengthening of barrier integrity is vital to homeostasis. Considering our data, we propose that activation of TC by the microbiota-produced succinate in the colon is a mechanism evolved by the host to counterbalance microbiome-derived cues that facilitate invasion by intestinal pathogens.}, }
@article {pmid38351748, year = {2024}, author = {Wang, J and Gao, Y and Ren, S and Li, J and Chen, S and Feng, J and He, B and Zhou, Y and Xuan, R}, title = {Gut microbiota-derived trimethylamine N-Oxide: a novel target for the treatment of preeclampsia.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2311888}, pmid = {38351748}, issn = {1949-0984}, mesh = {Animals ; Female ; Humans ; Mice ; Pregnancy ; Cohort Studies ; Endothelial Cells/metabolism ; *Gastrointestinal Microbiome ; Methylamines/metabolism ; *Pre-Eclampsia/therapy ; RNA, Ribosomal, 16S ; }, abstract = {Pre-eclampsia (PE) is the most common complication of pregnancy and seriously threatens the health and safety of the mother and child. Studies have shown that an imbalance in gut microbiota can affect the progression of PE. Trimethylamine N-oxide (TMAO) is an intestinal microbiota-derived metabolite that is thought to be involved in the occurrence of PE; however, its causal relationship and mechanism remain unclear. In this clinical cohort study, including 28 patients with eclampsia and 39 matched healthy controls, fecal samples were collected for 16S rRNA gene sequencing, and serum was collected for targeted metabolomics research. The results showed that the level of TMAO and the abundance of its source bacteria had significantly increased in patients with PE, and were positively correlated with the clinical progression of PE. Fecal microbiota transplantation (FMT) was applied to an antibiotic-depleted-treated mouse model and targeted inhibition of TMAO. The results of the FMT experiment revealed that mice that received fecal microbiota transplantation from patients with PE developed typical PE symptoms and increased oxidative stress and inflammatory damage, both of which were reversed by 3,3-Dimethyl-1-butanol (DMB), a TMAO inhibitor, which also improved pregnancy outcomes in the model mice. Similar results were obtained in the classical NG-Nitroarginine methyl ester (L-NAME) induced PE mouse model. Mechanistically, TMAO promotes the progression of PE by regulating inflammatory and oxidative stress-related signaling pathways, affecting the migration and angiogenesis of vascular endothelial cells, as well as the migration and invasion of trophoblast cells. Our results reveal the role and mechanism of gut microbiota and TMAO in the progression of PE, provides new ideas for exploring the pathogenesis and therapeutic targets of PE, and determines the potential application value of TMAO as a target for PE intervention.}, }
@article {pmid38350484, year = {2023}, author = {Yin, S and Liao, Y and Ma, Y and Han, X and Yang, Z and Fang, J and Alahmadi, RM and Hatamleh, AA and Duraipandiyan, V and Gurusunathan, VR and Arokiyaraj, S and Liu, G}, title = {Lactiplantibacillus plantarum and faecal microbiota transplantation can improve colitis in mice by affecting gut microbiota and metabolomics.}, journal = {Beneficial microbes}, volume = {14}, number = {6}, pages = {609-622}, doi = {10.1163/18762891-20230046}, pmid = {38350484}, issn = {1876-2891}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; *Probiotics/analysis ; *Colitis/chemically induced/therapy ; *Inflammatory Bowel Diseases/therapy ; *Lactobacillus plantarum/physiology ; Dextran Sulfate ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {Gut microbiota may have therapeutic effects on inflammatory bowel disease (IBD). Regulating intestinal microbiota through Lactiplantibacillus plantarum (L. plantarum) and faecal microbiota transplantation (FMT) is a novel approach to treating IBD. This study aimed to explore the effect of L. plantarum and FMT pretreatment in alleviating colitis in mice. Five groups of mice (n = 6 per group) were included: CON group, DSS group (dextran sodium sulphate-induced colitis mice), LP-DSS pretreatment group (colitis mice were given strain L. plantarum and 5% DSS), DSS-FMT group (mice pretreated with faecal microbiota transplantation were given 5% DSS), and LP-FMT pretreatment group (mice pretreated with faecal microbiota transplantation and L. plantarum were given 5% DSS). Serum metabolites and intestinal microbiota were analysed by 16S rRNA sequencing liquid chromatography-mass spectrometry (LC-MS). The results demonstrated that L. plantarum and FMT improved gut microbiota in mice by increasing Firmicutes and decreasing the Bacteroidetes. In the serum metabolomics analysis, there were 11 differential metabolites in the DSS-FMT and LP-FMT pretreatment groups, and these differential metabolites were mainly glycerophospholipids and sphingolipids. It is worth noting that Lachnospira and Lactobacillus were positively associated with 8 differential metabolites. These results suggest that L. plantarum and FMT can regulate intestinal microorganisms and serum metabolomics to alleviate inflammation.}, }
@article {pmid38347911, year = {2024}, author = {Zhou, X and Chen, R and Cai, Y and Chen, Q}, title = {Fecal Microbiota Transplantation: A Prospective Treatment for Type 2 Diabetes Mellitus.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {17}, number = {}, pages = {647-659}, pmid = {38347911}, issn = {1178-7007}, abstract = {PURPOSE OF REVIEW: The aim of this review is to summarize the role of gastrointestinal microbiome (GM) in the development of type 2 diabetes mellitus (T2DM). Besides, we discuss the feasibility of applying FMT in the treatment of T2DM and propose a series of processes to refine the use of FMT in the treatment of T2DM.<br><br>RECENT FINDINGS: T2DM is a metabolic disease which is connected with the GM. According to many researches, GM can produce a variety of metabolites such as bile acid, short chain fatty acids, lipopolysaccharides and trimethylamine oxide which play an important role in metabolism. FMT is a method to regulate GM and has been observed to be effective in the treatment of metabolic diseases such as T2DM in some mouse models and people. However, there is still a lack of direct evidence for the use of FMT in the treatment of T2DM, and the process of FMT is not standardized.<br><br>SUMMARY: Dysregulation of GM is closely related to the development of T2DM. Promoting the conversion of GM in T2DM patients to normal population through FMT can reduce insulin resistance and lower their blood glucose level, which is an optional treatment for T2DM patients in the future. At present, the feasibility and limitations of applying FMT to the treatment of T2DM need to be further studied.}, }
@article {pmid38347627, year = {2024}, author = {Behling, AH and Wilson, BC and Ho, D and Cutfield, WS and Vatanen, T and O'Sullivan, JM}, title = {Horizontal gene transfer after faecal microbiota transplantation in adolescents with obesity.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {26}, pmid = {38347627}, issn = {2049-2618}, mesh = {Adolescent ; Humans ; Fecal Microbiota Transplantation/methods ; Gene Transfer, Horizontal ; *Pediatric Obesity ; *Microbiota ; *Gastrointestinal Microbiome/genetics ; Bacteria/genetics ; Feces/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Horizontal gene transfer (HGT) describes the transmission of DNA outside of direct ancestral lineages. The process is best characterised within the bacterial kingdom and can enable the acquisition of genetic traits that support bacterial adaptation to novel niches. The adaptation of bacteria to novel niches has particular relevance for faecal microbiota transplantation (FMT), a therapeutic procedure which aims to resolve gut-related health conditions of individuals, through transplanted gut microbiota from healthy donors.<br><br>RESULTS: Three hundred eighty-one stool metagenomic samples from a placebo-controlled FMT trial for obese adolescents (the Gut Bugs Trial) were analysed for HGT, using two complementary methodologies. First, all putative HGT events, including historical HGT signatures, were quantified using the bioinformatics application WAAFLE. Second, metagenomic assembly and gene clustering were used to assess and quantify donor-specific genes transferred to recipients following the intervention. Both methodologies found no difference between the level of putative HGT events in the gut microbiomes of FMT and placebo recipients, post-intervention. HGT events facilitated by engrafted donor species in the FMT recipient gut at 6&#xa0;weeks post-intervention were identified and characterised. Bacterial strains contributing to this subset of HGT events predominantly belonged to the phylum Bacteroidetes. Engraftment-dependent horizontally transferred genes were retained within recipient microbiomes at 12 and 26&#xa0;weeks post-intervention.<br><br>CONCLUSION: Our study suggests that novel microorganisms introduced into the recipient gut following FMT have no impact on the basal rate of HGT within the human gut microbiome. Analyses of further FMT studies are required to assess the generalisability of this conclusion across different FMT study designs and for the treatment of different gut-related conditions. Video Abstract.}, }
@article {pmid38346843, year = {2024}, author = {}, title = {Correction: Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial.}, journal = {RMD open}, volume = {10}, number = {1}, pages = {}, doi = {10.1136/rmdopen-2023-003750corr1}, pmid = {38346843}, issn = {2056-5933}, }
@article {pmid38345223, year = {2024}, author = {Pett, N and Hunter, M and Carranza García, NA and Seo, JH and Collins, SR and Rohwer, F and Osborne, LC and Tropini, C}, title = {T4 Bacteriophage and E. coli Interaction in the Murine Intestine: A Prototypical Model for Studying Host-Bacteriophage Dynamics In Vivo.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {203}, pages = {}, doi = {10.3791/65906}, pmid = {38345223}, issn = {1940-087X}, mesh = {Humans ; Mice ; Animals ; *Bacteriophages/physiology ; Bacteriophage T4 ; Escherichia coli ; Gastrointestinal Tract/microbiology ; Intestines ; *Microbiota ; Bacteria ; }, abstract = {Bacteriophages (phages) are viruses that infect bacteria with species- and strain-level specificity and are the most abundant biological entities across all known ecosystems. Within bacterial communities, such as those found in the gut microbiota, phages are implicated in regulating microbiota population dynamics and driving bacterial evolution. There has been renewed interest in phage research in the last decade, in part due to the host-specific killing capabilities of lytic phages, which offer a promising tool to counter the increasing threat of antimicrobial resistant bacteria. Furthermore, recent studies demonstrating that phages adhere to intestinal mucus suggest they may have a protective role in preventing bacterial invasion into the underlying epithelium. Importantly, like bacterial microbiomes, disrupted phageomes have been associated with worsened outcomes in diseases such as inflammatory bowel disease. Previous studies have demonstrated that phages can modulate the microbiome of animals and humans through fecal filtrate transplants, benefiting the host's health. With this recent wave of research comes the necessity to establish and standardize protocols for studying phages in the context of the gut microbiome. This protocol provides a set of procedures to study isolated T4 phages and their bacterial host, Escherichia coli, in the context of the murine gastrointestinal tract. The methods described here outline how to start from a phage lysate, administer it to mice and assess effects on bacterial host and phage levels. This protocol can be modified and applied to other phage-bacterial pairs and provides a starting point for studying host-phage dynamics in vivo.}, }
@article {pmid38344334, year = {2024}, author = {Deac, I&#x15e; and Ofrim, AM and Fărcaş, RA and Grad, S and Popa, &#x15e;L and Dumitraşcu, DL}, title = {The management of Clostridioides difficile infection: from empirism to evidence.}, journal = {Medicine and pharmacy reports}, volume = {97}, number = {1}, pages = {5-11}, pmid = {38344334}, issn = {2668-0572}, abstract = {Clostridioides difficile infection (CDI) in clinical practice represents a challenge for its management and also prevention of recurrence. Even though there are updated guidelines for infection prevention, control and treatment, CDI remains a leading cause of healthcare acquired diarrhea with increasing incidence in the community. We present here a synthesis of the most recent international guidelines on the management of CDI. In 2021 updated guidelines on the treatment of CDI in adults were published by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA), American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). These guidelines focused on CDI management in adults, including new data on the clinical efficacy of Fidaxomicin (FDX) and Bezlotoxumab. The 2017 publication of IDSA and SHEA - Clinical Practice Guidelines for Clostridium difficile infection also included pediatric treatment recommendations that are not a part of the 2021 update. Vancomycin (VAN) treatment for an initial CDI episode remains an acceptable alternative to FDX, considering the monetary and logistical challenge of acquiring FDX. There is growing literature on fecal microbiota transplantation (FMT) and the 2021 guidelines describe its role in severe complicated refractory CDI cases and for which surgical management is not feasible. Moreover, there are new data on the secondary prophylaxis with VAN in refractory CDI in patients with risk factors who receive broad spectrum antibiotics.}, }
@article {pmid38344171, year = {2024}, author = {Zhu, H and Wang, W and Li, Y}, title = {The interplay between microbiota and brain-gut axis in epilepsy treatment.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1276551}, pmid = {38344171}, issn = {1663-9812}, abstract = {The brain-gut axis plays a vital role in connecting the cognitive and emotional centers of the brain with the intricate workings of the intestines. An imbalance in the microbiota-mediated brain-gut axis extends far beyond conditions like Irritable Bowel Syndrome (IBS) and obesity, playing a critical role in the development and progression of various neurological disorders, including epilepsy, depression, Alzheimer's disease (AD), and Parkinson's disease (PD). Epilepsy, a brain disorder characterized by unprovoked seizures, affects approximately 50 million people worldwide. Accumulating evidence suggests that rebuilding the gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and ketogenic diets (KD) can benefit drug-resistant epilepsy. The disturbances in the gut microbiota could contribute to the toxic side effects of antiepileptic drugs and the development of drug resistance in epilepsy patients. These findings imply the potential impact of the gut microbiota on epilepsy and suggest that interventions targeting the microbiota, such as the KD, hold promise for managing and treating epilepsy. However, the full extent of the importance of microbiota in epilepsy treatment is not yet fully understood, and many aspects of this field remain unclear. Therefore, this article aims to provide an overview of the clinical and animal evidence supporting the regulatory role of gut microbiota in epilepsy, and of potential pathways within the brain-gut axis that may be influenced by the gut microbiota in epilepsy. Furthermore, we will discuss the recent advancements in epilepsy treatment, including the KD, fecal microbiota transplantation, and antiseizure drugs, all from the perspective of the gut microbiota.}, }
@article {pmid38343539, year = {2024}, author = {Luqman, A and Hassan, A and Ullah, M and Naseem, S and Ullah, M and Zhang, L and Din, AU and Ullah, K and Ahmad, W and Wang, G}, title = {Role of the intestinal microbiome and its therapeutic intervention in cardiovascular disorder.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1321395}, pmid = {38343539}, issn = {1664-3224}, mesh = {Humans ; *Cardiovascular Diseases/therapy/etiology ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; *Hypertension/complications ; *Atherosclerosis/complications ; *Methylamines ; }, abstract = {The gut microbiome is a heterogeneous population of microbes comprising viruses, bacteria, fungi, and protozoa. Such a microbiome is essential for sustaining host equilibrium, and its impact on human health can be altered by a variety of factors such as external variables, social behavior, age, nutrition, and genetics. Gut microbes' imbalances are related to a variety of chronic diseases including cancer, obesity, and digestive disorders. Globally, recent findings show that intestinal microbes have a significant role in the formation of cardiovascular disease (CVD), which is still the primary cause of fatalities. Atherosclerosis, hypertension, diabetes, inflammation, and some inherited variables are all cardiovascular risk variables. However, studies found correlations between metabolism, intestinal flora, and dietary intake. Variations in the diversity of gut microbes and changes in their activity are thought to influence CVD etiology. Furthermore, the gut microbiota acts as an endocrine organ, producing bioactive metabolites such as TMA (trimethylamine)/TMAO (trimethylamine N-oxide), SCFA (short-chain fatty acids), and bile acids, which have a substantial impact on host wellness and disease by multiple mechanisms. The purpose of this overview is to compile current evidence highlighting the intricate links between gut microbiota, metabolites, and the development of CVD. It focuses on how intestinal dysbiosis promotes CVD risk factors such as heart failure, hypertension, and atherosclerosis. This review explores the normal physiology of intestinal microbes and potential techniques for targeting gut bacteria for CVD treatment using various microbial metabolites. It also examines the significance of gut bacteria in disease treatment, including supplements, prebiotics, probiotics, antibiotic therapies, and fecal transplantation, which is an innovative approach to the management of CVD. As a result, gut bacteria and metabolic pathways become increasingly attractive as potential targets for CVD intervention.}, }
@article {pmid38340564, year = {2024}, author = {Sun, H and Yang, B and Zhu, X and Li, Q and Song, E and Song, Y}, title = {Oral exposure of polystyrene microplastics and doxycycline affects mice neurological function via gut microbiota disruption: The orchestrating role of fecal microbiota transplantation.}, journal = {Journal of hazardous materials}, volume = {467}, number = {}, pages = {133714}, doi = {10.1016/j.jhazmat.2024.133714}, pmid = {38340564}, issn = {1873-3336}, mesh = {Humans ; Animals ; Mice ; *Doxycycline/toxicity ; *Gastrointestinal Microbiome ; Microplastics/toxicity ; Plastics ; Polystyrenes/toxicity ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/toxicity ; }, abstract = {The debris of plastics with a size < 5 mm, called microplastics, possess long-lived legacies of plastic pollution and a growing threat to human beings. The adverse effects and corresponding molecular mechanisms of microplastics are still largely unknown and must be prioritized. Antibiotics commonly co-existed with microplastics; the current study investigated the syngenetic toxic effect of doxycycline (Dox) and polystyrene microplastics (PS). Specifically, we found that Dox combined with PS exposure perturbed gut microbiota homeostasis in mice, which mediated brain lesions and inflammation with a concomitant decline in learning and memory behaviors through the gut-brain axis. Of note, PS exposure resulted in intestinal damage and structural change, but Dox did not accelerate the disruption of intestinal barrier integrity in PS-treated mice. Interestingly, fecal microbiota transplantation (FMT) can reverse neurological impairment caused by combined PS and Dox exposure via compensating gut microbes; therefore, the learning and memory abilities of mice were also recovered. This work not only provides insights into the syngenetic effect of microplastics and antibiotics and highlights their distal neurotoxicity through the gut-brain axis but also offers a promising strategy against their combined toxicity.}, }
@article {pmid38339251, year = {2024}, author = {Vongsavath, T and Rahmani, R and Tun, KM and Manne, V}, title = {The Use of Fecal Microbiota Transplant in Overcoming and Modulating Resistance to Anti-PD-1 Therapy in Patients with Skin Cancer.}, journal = {Cancers}, volume = {16}, number = {3}, pages = {}, pmid = {38339251}, issn = {2072-6694}, abstract = {While immune checkpoint inhibitors have evolved into the standard of care for advanced melanoma, 40-50% of melanoma cases progress while on therapies. The relationship between bacterium and carcinogenesis is well founded, such as in H. pylori in gastric cancers, and Fusobacterium in colorectal cancers. This interplay between dysbiosis and carcinogenesis questions whether changes in the microbiome could affect treatment. Thus, FMT may find utility in modifying the efficacy of anti-PD-1. This review aims to examine the use of FMT in treatment-resistant melanoma. A literature search was performed using the keywords "fecal microbiota transplant" and "skin cancer". Studies were reviewed for inclusion criteria and quality and in the final stage, and three studies were included. Overall objective responses were reported in 65% of patients who were able to achieve CR, and 45% who achieved PR. Clinical benefit rate of combined CR/PR with stable disease greater or equal to 6 months was 75%. Reported objective responses found durable stable disease lasting 12 months. Overall survival was 7 months, and overall PRS was 3 months. As for the evaluation of safety, many patients reported grade 1-2 FMT related AE. Only following the administration of anti-PD-1 therapy were there a grade 3 or higher AE.}, }
@article {pmid38339169, year = {2024}, author = {Chechushkov, A and Desyukevich, P and Yakovlev, T and Al Allaf, L and Shrainer, E and Morozov, V and Tikunova, N}, title = {Sterile Fecal Microbiota Transplantation Boosts Anti-Inflammatory T-Cell Response in Ulcerative Colitis Patients.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38339169}, issn = {1422-0067}, support = {21-14-00360//Russian Science Foundation/ ; }, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy/etiology ; Quality of Life ; *Gastrointestinal Microbiome ; Feces ; Anti-Inflammatory Agents ; T-Lymphocytes, Helper-Inducer ; }, abstract = {Ulcerative colitis is a chronic immune-mediated disease of unclear etiology, affecting people of different ages and significantly reducing the quality of life. Modern methods of therapy are mainly represented by anti-inflammatory drugs and are not aimed at a specific pathogenetic factor. In this study, we investigated the effect of transplantation of sterile stool filtrate from healthy donors on the induction of anti-inflammatory immune mechanisms. It was shown that performing such a procedure in patients with ulcerative colitis caused the appearance of T helper cells in the blood, which reacted to the content of sterile stool filtrates in an antigen-specific manner and produced IL-10. At the same time, cells of the same patients before therapy in response to the addition of sterile stool filtrates were less reactive and predominantly produced IL-4, indicating its pro-inflammatory skewing. The obtained data demonstrated the effect of an anti-inflammatory shift in the T-helper response after transplantation of sterile stool filtrate, which increased and persisted for at least three months after the procedure.}, }
@article {pmid38334893, year = {2024}, author = {Singh, A and Midha, V and Chauhan, NS and Sood, A}, title = {Current perspectives on fecal microbiota transplantation in inflammatory bowel disease.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {43}, number = {1}, pages = {129-144}, pmid = {38334893}, issn = {0975-0711}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Inflammatory Bowel Diseases/therapy/complications ; *Clostridium Infections/therapy/complications ; Longitudinal Studies ; Inflammation/complications ; Dysbiosis/therapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic modality within the domain of inflammatory bowel disease (IBD). While FMT has secured approval and demonstrated efficacy in addressing recurrent and refractory Clostridioides difficile infection, its application in IBD remains an area of active exploration and research. The current status of FMT in IBD reflects a nuanced landscape, with ongoing investigations delving into its effectiveness, safety and optimal implementation. Early-stage clinical trials and observational studies have provided insights into the potential of FMT to modulate the dysbiotic gut microbiota associated with IBD, aiming to mitigate inflammation and promote mucosal healing. However, considerable complexities persist, including variations in donor selection, treatment protocols and outcome assessments. Challenges in standardizing FMT protocols for IBD treatment are compounded by the dynamic nature of the gut microbiome and the heterogeneity of IBD itself. Despite these challenges, enthusiasm for FMT in IBD emanates from its capacity to address gut microbial dysbiosis, signifying a paradigm shift towards more comprehensive approaches in IBD management. As ongoing research progresses, an enhanced understanding of FMT's role in IBD therapy is anticipated. This article synthesizes the current status of FMT in IBD, elucidating the attendant challenges and aspiring towards the refinement of its application for improved patient outcomes.}, }
@article {pmid38334013, year = {2024}, author = {Liu, Y and Li, Z and Sun, T and Li, Z and Manyande, A and Xiang, H and He, Z}, title = {Gut microbiota regulates hepatic ischemia-reperfusion injury-induced cognitive dysfunction via the HDAC2-ACSS2 axis in mice.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {30}, number = {2}, pages = {e14610}, pmid = {38334013}, issn = {1755-5949}, support = {81670240//National Natural Science Foundation of China/ ; 81873467//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; Acetates/metabolism ; *Cognitive Dysfunction/etiology/metabolism ; Dysbiosis/complications ; *Gastrointestinal Microbiome ; Liver/metabolism ; Mice, Inbred C57BL ; *Reperfusion Injury/complications/metabolism ; }, abstract = {AIMS: Hepatic ischemia-reperfusion injury (HIRI) resulting from hepatic inflow occlusion, which is a common procedure in liver surgery is inevitable. Previous research has confirmed that the cognitive dysfunction induced by HIRI is closely related to dysbiosis of the gut microbiota. This research aims to investigate the mechanisms underlying this complication.<br><br>METHODS: C57BL/6 mice underwent hepatic ischemia experimentally through the occlusion of the left hepatic artery and portal vein. To assess the HDAC2-ACSS2 axis, gut microbiota transplantation. Enzyme-linked immunosorbent assay and LC/MS short-chain fatty acid detection were utilized.<br><br>RESULTS: The findings indicated a notable decline in ACSS2 expression in the hippocampus of mice experiencing hepatic ischemia-reperfusion injury, emphasizing the compromised acetate metabolism in this particular area. Furthermore, the cognitive impairment phenotype and the dysregulation of the HDAC2-ACSS2 axis could also be transmitted to germ-free mice via fecal microbial transplantation. Enzyme-linked immunosorbent assay revealed reduced Acetyl-coenzyme A (acetyl-CoA) and Acetylated lysine levels in the hippocampus.<br><br>CONCLUSION: These findings suggest that acetate metabolism is impaired in the hippocampus of HIRI-induced cognitive impairment mice and related to dysbiosis, leading to compromised histone acetylation.}, }
@article {pmid38332676, year = {2024}, author = {Jiang, Y and Wang, X and Chen, J and Zhang, Y and Hashimoto, K and Yang, JJ and Zhou, Z}, title = {Repeated (S)-ketamine administration ameliorates the spatial working memory impairment in mice with chronic pain: role of the gut microbiota-brain axis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2310603}, pmid = {38332676}, issn = {1949-0984}, mesh = {Mice ; Animals ; *Ketamine/pharmacology/therapeutic use ; Brain-Derived Neurotrophic Factor/genetics/metabolism/pharmacology ; Memory, Short-Term ; *Gastrointestinal Microbiome ; *Chronic Pain/drug therapy ; RNA, Ribosomal, 16S ; Hippocampus/metabolism ; Memory Disorders/drug therapy ; Butyrates/pharmacology ; }, abstract = {Chronic pain is commonly linked with diminished working memory. This study explores the impact of the anesthetic (S)-ketamine on spatial working memory in a chronic constriction injury (CCI) mouse model, focusing on gut microbiome. We found that multiple doses of (S)-ketamine, unlike a single dose, counteracted the reduced spontaneous alteration percentage (%SA) in the Y-maze spatial working memory test, without affecting mechanical or thermal pain sensitivity. Additionally, repeated (S)-ketamine treatments improved the abnormal composition of the gut microbiome (β-diversity), as indicated by fecal 16S rRNA analysis, and increased levels of butyrate, a key gut - brain axis mediator. Protein analysis showed that these treatments also corrected the upregulated histone deacetylase 2 (HDAC2) and downregulated brain-derived neurotrophic factor (BDNF) in the hippocampi of CCI mice. Remarkably, fecal microbiota transplantation from mice treated repeatedly with (S)-ketamine to CCI mice restored %SA and hippocampal BDNF levels in CCI mice. Butyrate supplementation alone also improved %SA, BDNF, and HDAC2 levels in CCI mice. Furthermore, the TrkB receptor antagonist ANA-12 negated the beneficial effects of repeated (S)-ketamine on spatial working memory impairment in CCI mice. These results indicate that repeated (S)-ketamine administration ameliorates spatial working memory impairment in CCI mice, mediated by a gut microbiota - brain axis, primarily through the enhancement of hippocampal BDNF - TrkB signaling by butyrate.}, }
@article {pmid38331095, year = {2024}, author = {Lin, Q and Kuypers, M and Baglaenko, Y and Cao, E and Hezaveh, K and Despot, T and de Amat Herbozo, C and Cruz Tleugabulova, M and Umaña, JM and McGaha, TL and Philpott, DJ and Mallevaey, T}, title = {The intestinal microbiota modulates the transcriptional landscape of iNKT cells at steady-state and following antigen exposure.}, journal = {Mucosal immunology}, volume = {17}, number = {2}, pages = {226-237}, doi = {10.1016/j.mucimm.2024.02.002}, pmid = {38331095}, issn = {1935-3456}, mesh = {Male ; Female ; Mice ; Animals ; *Natural Killer T-Cells ; *Gastrointestinal Microbiome ; Antigens ; Inflammation ; *Colitis ; Lymphocyte Activation ; }, abstract = {Invariant Natural Killer T (iNKT) cells are unconventional T cells that respond to microbe-derived glycolipid antigens. iNKT cells exert fast innate effector functions that regulate immune responses in a variety of contexts, including during infection, cancer, or inflammation. The roles these unconventional T cells play in intestinal inflammation remain poorly defined and vary based on the disease model and species. Our previous work suggested that the gut microbiota influenced iNKT cell functions during dextran sulfate sodium-induced colitis in mice. This study, shows that iNKT cell homeostasis and response following activation are altered in germ-free mice. Using prenatal fecal transplant in specific pathogen-free mice, we show that the transcriptional signatures of iNKT cells at steady state and following αGC-mediated activation in vivo are modulated by the microbiota. Our data suggest that iNKT cells sense the microbiota at homeostasis independently of their T cell receptors. Finally, iNKT cell transcriptional signatures are different in male and female mice. Collectively, our findings suggest that sex and the intestinal microbiota are important factors that regulate iNKT cell homeostasis and responses. A deeper understanding of microbiota-iNKT cell interactions and the impact of sex could improve the development of iNKT cell-based immunotherapies.}, }
@article {pmid38329942, year = {2024}, author = {Zhan, K and Wu, H and Xu, Y and Rao, K and Zheng, H and Qin, S and Yang, Y and Jia, R and Chen, W and Huang, S}, title = {The function of the gut microbiota-bile acid-TGR5 axis in diarrhea-predominant irritable bowel syndrome.}, journal = {mSystems}, volume = {9}, number = {3}, pages = {e0129923}, pmid = {38329942}, issn = {2379-5077}, support = {81974563, 81703992, 81904148//MOST | National Natural Science Foundation of China (NSFC)/ ; No.SZ2022QN08//Guangdong Provincial Academy of Chinese Medical Sciences/ ; 202102010226, 202102010207, 2023A03J0733, 2023A03J0735//Bureau of Science and Information Technology of Guangzhou Municipality | Guangzhou Municipal Science and Technology Project (Guangzhou Science and Technology Plan)/ ; }, mesh = {Humans ; Rats ; Animals ; *Irritable Bowel Syndrome/metabolism ; Bile Acids and Salts ; *Gastrointestinal Microbiome ; Diarrhea/etiology ; Intestinal Mucosa/metabolism ; Chenodeoxycholic Acid/pharmacology ; *Hypersensitivity/complications ; *Bacteroides ; }, abstract = {UNLABELLED: Imbalanced gut microbiota (GM) and abnormal fecal bile acid (BA) are thought to be the key factors for diarrhea-predominant irritable bowel syndrome (IBS-D), but the underlying mechanism remains unclear. Herein, we explore the influence of the GM-BA-Takeda G-protein-coupled receptor 5 (TGR5) axis on IBS-D. Twenty-five IBS-D patients and fifteen healthy controls were recruited to perform BA-related metabolic and metagenomic analyses. Further, the microbiota-humanized IBS-D rat model was established by fecal microbial transplantation (FMT) to investigate the GM-BA-TGR5 axis effects on the colonic barrier and visceral hypersensitivity (VH) in IBS-D. Finally, we used chenodeoxycholic acid (CDCA), an important BA screened out by metabolome, to evaluate whether it affected diarrhea and VH via the TGR5 pathway. Clinical research showed that GM associated with bile salt hydrolase (BSH) activity such as Bacteroides ovatus was markedly reduced in the GM of IBS-D, accompanied by elevated total and primary BA levels. Moreover, we found that CDCA not only was increased as the most important primary BA in IBS-D patients but also could induce VH through upregulating TGR5 in the colon and ileum of normal rats. TGR5 inhibitor could reverse the phenotype, depression-like behaviors, pathological change, and level of fecal BSH in a microbiota-humanized IBS-D rat model. Our findings proved that human-associated FMT could successfully induce the IBS-D rat model, and the imbalanced GM-BA-TGR5 axis may promote colonic mucosal barrier dysfunction and enhance VH in IBS-D.<br><br>IMPORTANCE: Visceral hypersensitivity and intestinal mucosal barrier damage are important factors that cause abnormal brain-gut interaction in diarrhea-predominant irritable bowel syndrome (IBS-D). Recently, it was found that the imbalance of the gut microbiota-bile acid axis is closely related to them. Therefore, understanding the structure and function of the gut microbiota and bile acids and the underlying mechanisms by which they shape visceral hypersensitivity and mucosal barrier damage in IBS-D is critical. An examination of intestinal feces from IBS-D patients revealed that alterations in gut microbiota and bile acid metabolism underlie IBS-D and symptom onset. We also expanded beyond existing knowledge of well-studied gut microbiota and bile acid and found that Bacteroides ovatus and chenodeoxycholic acid may be potential bacteria and bile acid involved in the pathogenesis of IBS-D. Moreover, our data integration reveals the influence of the microbiota-bile acid-TGR5 axis on barrier function and visceral hypersensitivity.}, }
@article {pmid38329115, year = {2024}, author = {Kesh, K and Tao, J and Ghosh, N and Jalodia, R and Singh, S and Dawra, R and Roy, S}, title = {Prescription opioids induced microbial dysbiosis worsens severity of chronic pancreatitis and drives pain hypersensitivity.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2310291}, pmid = {38329115}, issn = {1949-0984}, support = {R01 DK117576/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Mice ; Analgesics, Opioid/adverse effects ; Oxycodone/adverse effects ; Dysbiosis/chemically induced/drug therapy ; Ceruletide/adverse effects ; *Gastrointestinal Microbiome/physiology ; Mice, Inbred C57BL ; *Pancreatitis, Chronic/chemically induced/drug therapy/pathology ; Morphine/adverse effects ; Pain/drug therapy ; Inflammation ; }, abstract = {Opioids, such as morphine and oxycodone, are widely used for pain management associated with chronic pancreatitis (CP); however, their impact on the progression and pain sensitivity of CP has never been evaluated. This report investigates the impact of opioid use on the severity of CP, pain sensitivity, and the gut microbiome. C57BL/6 mice were divided into control, CP, CP with morphine/oxycodone, and either morphine or oxycodone alone groups. CP was induced by administration of caerulein (50ug/kg/h, i.p. hourly x7, twice a week for 10 weeks). The mouse-to-pancreas weight ratio, histology, and Sirius red staining were performed to measure CP severity. Tail flick and paw pressure assays were used to measure thermal and mechanical pain. DNA was extracted from the fecal samples and subjected to whole-genome shotgun sequencing. Germ-free mice were used to validate the role of gut microbiome in sensitizing acute pancreatic inflammation. Opioid treatment exacerbates CP by increasing pancreatic necrosis, fibrosis, and immune-cell infiltration. Opioid-treated CP mice exhibited enhanced pain hypersensitivity and showed distinct clustering of the gut microbiome compared to untreated CP mice, with severely compromised gut barrier integrity. Fecal microbiota transplantation (FMT) from opioid-treated CP mice into germ-free mice resulted in pancreatic inflammation in response to a suboptimal caerulein dose. Together, these analyses revealed that opioids worsen the severity of CP and induce significant alterations in pain sensitivity and the gut microbiome in a caerulein CP mouse model. Microbial dysbiosis plays an important role in sensitizing the host to pancreatic inflammation.}, }
@article {pmid38328082, year = {2024}, author = {Gray, SM and Moss, AD and Herzog, JW and Kashiwagi, S and Liu, B and Young, JB and Sun, S and Bhatt, A and Fodor, AA and Balfour Sartor, R}, title = {Mouse Adaptation of Human Inflammatory Bowel Diseases Microbiota Enhances Colonization Efficiency and Alters Microbiome Aggressiveness Depending on Recipient Colonic Inflammatory Environment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38328082}, issn = {2692-8205}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; }, abstract = {Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis. Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10[-/-] mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10[-/-] mice. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10[-/-] host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10[-/-] mice than the distinct microbiota reassembled in non-inflamed WT hosts. Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer.}, }
@article {pmid38328040, year = {2024}, author = {Bauer, KC and Trehan, R and Ruf, B and Myojin, Y and Benmebarek, MR and Ma, C and Seifert, M and Nur, A and Qi, J and Huang, P and Soliman, M and Green, BL and Wabitsch, S and Springer, DA and Rodriguez-Matos, FJ and Ghabra, S and Gregory, SN and Matta, J and Dawson, B and Golino, J and Xie, C and Dzutsev, A and Trinchieri, G and Korangy, F and Greten, TF}, title = {The Gut Microbiome Controls Liver Tumors via the Vagus Nerve.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.23.576951}, pmid = {38328040}, issn = {2692-8205}, abstract = {Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8 [+] T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.}, }
@article {pmid38325336, year = {2024}, author = {She, J and Tuerhongjiang, G and Guo, M and Liu, J and Hao, X and Guo, L and Liu, N and Xi, W and Zheng, T and Du, B and Lou, B and Gao, X and Yuan, X and Yu, Y and Zhang, Y and Gao, F and Zhuo, X and Xiong, Y and Zhang, X and Yu, J and Yuan, Z and Wu, Y}, title = {Statins aggravate insulin resistance through reduced blood glucagon-like peptide-1 levels in a microbiota-dependent manner.}, journal = {Cell metabolism}, volume = {36}, number = {2}, pages = {408-421.e5}, doi = {10.1016/j.cmet.2023.12.027}, pmid = {38325336}, issn = {1932-7420}, mesh = {Humans ; Animals ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/therapeutic use ; *Insulin Resistance ; Atorvastatin/pharmacology/therapeutic use ; Glucagon-Like Peptide 1 ; *Glucose Intolerance/drug therapy ; Bile Acids and Salts ; Ursodeoxycholic Acid/pharmacology/therapeutic use ; *Microbiota ; }, abstract = {Statins are currently the most common cholesterol-lowering drug, but the underlying mechanism of statin-induced hyperglycemia is unclear. To investigate whether the gut microbiome and its metabolites contribute to statin-associated glucose intolerance, we recruited 30 patients with atorvastatin and 10 controls, followed up for 16 weeks, and found a decreased abundance of the genus Clostridium in feces and altered serum and fecal bile acid profiles among patients with atorvastatin therapy. Animal experiments validated that statin could induce glucose intolerance, and transplantation of Clostridium sp. and supplementation of ursodeoxycholic acid (UDCA) could ameliorate statin-induced glucose intolerance. Furthermore, oral UDCA administration in humans alleviated the glucose intolerance without impairing the lipid-lowering effect. Our study demonstrated that the statin-induced hyperglycemic effect was attributed to the Clostridium sp.-bile acids axis and provided important insights into adjuvant therapy of UDCA to lower the adverse risk of statin therapy.}, }
@article {pmid38324560, year = {2024}, author = {Barko, P and Nguyen-Edquilang, J and Williams, DA and Gal, A}, title = {Fecal microbiome composition and diversity of cryopreserved canine stool at different duration and storage conditions.}, journal = {PloS one}, volume = {19}, number = {2}, pages = {e0294730}, pmid = {38324560}, issn = {1932-6203}, mesh = {Humans ; Dogs ; Animals ; *Specimen Handling ; Feces/microbiology ; *Microbiota ; Cryopreservation/veterinary ; Gastrointestinal Tract ; Bacteria/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Fresh-frozen stool banks intended for humans with gastrointestinal and metabolic disorders have been recently established and there are ongoing efforts to establish the first veterinary fresh-frozen stool bank. Fresh frozen stored feces provide an advantage of increased availability and accessibility to high-quality optimal donor fecal material. The stability of frozen canine feces regarding fecal microbiome composition and diversity has not been reported in dogs, providing the basis for this study. We hypothesized that fecal microbial composition and diversity of healthy dogs would remain stable when stored at -20°C and -80°C for up to 12 months compared to baseline samples evaluated before freezing. Stool samples were collected from 20 apparently healthy dogs, manually homogenized, cryopreserved in 20% glycerol and aliquoted, frozen in liquid nitrogen and stored at -20°C or -80°C for 3, 6, 9, and 12 months. At baseline and after period of storage, aliquots were thawed and treated with propidium monoazide before fecal DNA extraction. Following long-read 16S-rRNA amplicon sequencing, bacterial community composition and diversity were compared among treatment groups. We demonstrated that fresh-frozen canine stools collected from 20 apparently healthy dogs could be stored for up to 12 months at -80°C with minimal change in microbial community composition and diversity and that storage at -80°C is superior to storage at -20°C. We also found that differences between dogs had the largest effect on community composition and diversity. Relative abundances of certain bacterial taxa, including those known to be short-chain fatty acid producers, varied significantly with specific storage temperatures and duration. Further work is required to ascertain whether fecal donor material that differs in bacterial community composition and diversity across storage conditions and duration could lead to differences in clinical efficacy for specific clinical indications of fecal microbiota transplantation.}, }
@article {pmid38323255, year = {2024}, author = {Prayag, PS and Patwardhan, SA and Ajapuje, PS and Melinkeri, S and Gadhikar, H and Palnitkar, S and Simbasivam, R and Joshi, RS and Baheti, A and Sheth, US and Prayag, AP}, title = {Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India.}, journal = {Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine}, volume = {28}, number = {2}, pages = {106-110}, pmid = {38323255}, issn = {0972-5229}, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is an emerging option for recurrent or refractory Clostridium difficile-associated diarrhea (CDAD). We describe a single-center experience of FMT in hematopoietic stem cell transplant (HSCT) recipients with CDAD in India.<br><br>METHODS: A prospective observational study of HSCT recipients with CDAD who received FMT in our center.<br><br>RESULTS: A total of 13 patients were included. All the patients were allogenic HSCT recipients; FMT was performed in seven patients due to refractory CDAD, in five patients due to the presence of both CDAD and graft vs host disease (GVHD), and in 1 patient due to recurrent CDAD. The approach to FMT was colonoscopic in 10 (77%) patients. Only one patient reported bacteremia and one patient had candidemia, both of which were unrelated to FMT. Of the 10 patients who had complete resolution of CDAD, only one patient presented with a recurrence of CDAD within 8 weeks post-FMT.<br><br>CONCLUSION: This is the first study from India using FMT as a therapeutic modality for CDAD in the setting of HSCT. Here we demonstrate that FMT in India is an effective option, especially when patients have refractory CDAD, recurrent CDAD, or both GVHD and CDAD. Further studies should explore the efficacy and feasibility of FMT in India.<br><br>HOW TO CITE THIS ARTICLE: Prayag PS, Patwardhan SA, Ajapuje PS, Melinkeri S, Gadhikar H, Palnitkar S, et al. Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India. Indian J Crit Care Med 2024;28(2):106-110.}, }
@article {pmid38323251, year = {2024}, author = {Gopal, PB}, title = {Lurking Danger: Emerging Evidence.}, journal = {Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine}, volume = {28}, number = {2}, pages = {93-94}, pmid = {38323251}, issn = {0972-5229}, abstract = {How to cite this article: Gopal PB. Lurking Danger: Emerging Evidence. Indian J Crit Care Med 2024;28(2):93-94.}, }
@article {pmid38322428, year = {2024}, author = {Wolstenholme, JT and Duong, NK and Brocato, ER and Bajaj, JS}, title = {Gut-Liver-Brain Axis and Alcohol Use Disorder: Treatment Potential of Fecal Microbiota Transplantation.}, journal = {Alcohol research : current reviews}, volume = {44}, number = {1}, pages = {01}, pmid = {38322428}, issn = {2169-4796}, support = {R21 TR003095/TR/NCATS NIH HHS/United States ; I01 CX001076/CX/CSRD VA/United States ; R01 AA026347/AA/NIAAA NIH HHS/United States ; P50 AA022537/AA/NIAAA NIH HHS/United States ; R01 AA029398/AA/NIAAA NIH HHS/United States ; }, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Alcoholism ; *Non-alcoholic Fatty Liver Disease/therapy ; *Liver Diseases, Alcoholic/therapy ; Alcohol Drinking ; }, abstract = {PURPOSE: Chronic alcohol use is a major cause of liver damage and death. In the United States, multiple factors have led to low utilization of pharmacotherapy for alcohol use disorder (AUD), including lack of provider knowledge and comfort in prescribing medications for AUD. Alcohol consumption has direct effects on the gut microbiota, altering the diversity of bacteria and leading to bacterial overgrowth. Growing evidence suggests that alcohol's effects on the gut microbiome may contribute to increased alcohol consumption and progression of alcohol-associated liver disease (ALD). This article reviews human and preclinical studies investigating the role of fecal microbiota transplantation (FMT) in ameliorating alcohol-associated alterations to the liver, gut, and brain resulting in altered behavior; it also discusses the therapeutic potential of FMT.<br><br>SEARCH METHODS: For this narrative review, a literature search was conducted in September 2022 of PubMed, Web of Science Core Collection, and Google Scholar to identify studies published between January 2012 and September 2022. Search terms used included "fecal microbiota transplantation" and "alcohol."<br><br>SEARCH RESULTS: Most results of the literature search were review articles or articles on nonalcoholic fatty liver disease; these were excluded. Of the remaining empirical manuscripts, very few described clinical or preclinical studies that were directly investigating the effects of FMT on alcohol drinking or related behaviors. Ultimately, 16 studies were included in the review.<br><br>DISCUSSION AND CONCLUSIONS: The literature search identified only a few studies that were directly investigating the effect of FMT on ALD or alcohol drinking and related behaviors. Largely proof-of-concept studies, these findings demonstrate that alcohol can alter the gut microbiome and that the microbiome can be transferred between humans and rodents to alter affective behaviors frequently associated with increased alcohol use. Other studies have shown promise of FMT or other probiotic supplementation in alleviating some of the symptoms associated with ALD and drinking. These results show that the implementation of FMT as a therapeutic approach is still in the investigatory stages.}, }
@article {pmid38322318, year = {2024}, author = {Feng, P and Xue, X and Bukhari, I and Qiu, C and Li, Y and Zheng, P and Mi, Y}, title = {Gut microbiota and its therapeutic implications in tumor microenvironment interactions.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1287077}, pmid = {38322318}, issn = {1664-302X}, abstract = {The development of cancer is not just the growth and proliferation of a single transformed cell, but its tumor microenvironment (TME) also coevolves with it, which is primarily involved in tumor initiation, development, metastasis, and therapeutic responses. Recent years, TME has been emerged as a potential target for cancer diagnosis and treatment. However, the clinical efficacy of treatments targeting the TME, especially its specific components, remains insufficient. In parallel, the gut microbiome is an essential TME component that is crucial in cancer immunotherapy. Thus, assessing and constructing frameworks between the gut microbiota and the TME can significantly enhance the exploration of effective treatment strategies for various tumors. In this review the role of the gut microbiota in human cancers, including its function and relationship with various tumors was summarized. In addition, the interaction between the gut microbiota and the TME as well as its potential applications in cancer therapeutics was described. Furthermore, it was summarized that fecal microbiota transplantation, dietary adjustments, and synthetic biology to introduce gut microbiota-based medical technologies for cancer treatment. This review provides a comprehensive summary for uncovering the mechanism underlying the effects of the gut microbiota on the TME and lays a foundation for the development of personalized medicine in further studies.}, }
@article {pmid38320845, year = {2024}, author = {Tweedie-Cullen, RY and Leong, K and Wilson, BC and Derraik, JGB and Albert, BB and Monk, R and Vatanen, T and Creagh, C and Depczynski, M and Edwards, T and Beck, K and Thabrew, H and O'Sullivan, JM and Cutfield, WS}, title = {Protocol for the Gut Bugs in Autism Trial: a double-blind randomised placebo-controlled trial of faecal microbiome transfer for the treatment of gastrointestinal symptoms in autistic adolescents and adults.}, journal = {BMJ open}, volume = {14}, number = {2}, pages = {e074625}, pmid = {38320845}, issn = {2044-6055}, mesh = {Adult ; Humans ; Adolescent ; *Autistic Disorder/therapy ; *Autism Spectrum Disorder/therapy ; Fecal Microbiota Transplantation/methods ; Quality of Life ; *Gastrointestinal Diseases/therapy ; Double-Blind Method ; *Gastrointestinal Microbiome ; Treatment Outcome ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Autism (formally autism spectrum disorder) encompasses a group of complex neurodevelopmental conditions, characterised by differences in communication and social interactions. Co-occurring chronic gastrointestinal symptoms are common among autistic individuals and can adversely affect their quality of life. This study aims to evaluate the efficacy of oral encapsulated faecal microbiome transfer (FMT) in improving gastrointestinal symptoms and well-being among autistic adolescents and adults.<br><br>METHODS AND ANALYSIS: This double-blind, randomised, placebo-controlled trial will recruit 100 autistic adolescents and adults aged 16-45 years, who have mild to severe gastrointestinal symptoms (Gastrointestinal Symptoms Rating Scale (GSRS) score &#x2265;2.0). We will also recruit eight healthy donors aged 18-32 years, who will undergo extensive clinical screening. Recipients will be randomised 1:1 to receive FMT or placebo, stratified by biological sex. Capsules will be administered over two consecutive days following an overnight bowel cleanse with follow-up assessments at 6, 12 and 26 weeks post-treatment. The primary outcome is GSRS score at 6 weeks. Other assessments include anthropometry, body composition, hair cortisol concentration, gut microbiome profile, urine/plasma gut-derived metabolites, plasma markers of gut inflammation/permeability and questionnaires on general well-being, sleep quality, physical activity, food diversity and treatment tolerability. Adverse events will be recorded and reviewed by an independent data monitoring committee.<br><br>ETHICS AND DISSEMINATION: Ethics approval for the study was granted by the Central Health and Disability Ethics Committee on 24 August 2021 (reference number: 21/CEN/211). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12622000015741.}, }
@article {pmid38319728, year = {2024}, author = {Yu, X and Ou, J and Wang, L and Li, Z and Ren, Y and Xie, L and Chen, Z and Liang, J and Shen, G and Zou, Z and Zhao, C and Li, G and Hu, Y}, title = {Gut microbiota modulate CD8[+] T cell immunity in gastric cancer through Butyrate/GPR109A/HOPX.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2307542}, pmid = {38319728}, issn = {1949-0984}, mesh = {Humans ; Mice ; Animals ; Butyrates/metabolism ; *Gastrointestinal Microbiome/physiology ; CD8-Positive T-Lymphocytes ; *Stomach Neoplasms ; Fatty Acids, Volatile/metabolism ; Butyric Acid ; Claudins ; }, abstract = {The gut microbiota and Short-chain fatty acids (SCFAs) can influence the progression of diseases, yet the role of these factors on gastric cancer (GC) remains uncertain. In this work, the analysis of the gut microbiota composition and SCFA content in the blood and feces of both healthy individuals and GC patients indicated that significant reductions in the abundance of intestinal bacteria involved in SCFA production were observed in GC patients compared with the controls. ABX mice transplanted with fecal microbiota from GC patients developed more tumors during the induction of GC and had lower levels of butyric acid. Supplementation of butyrate during the induction of gastric cancer along with H. pylori and N-methyl-N-nitrosourea (MNU) in WT in GPR109A[-/-]mice resulted in fewer tumors and more IFN-γ[+] CD8[+] T cells, but this effect was significantly weakened after knockout of GPR109A. Furthermore, In vitro GC cells and co-cultured CD8[+] T cells or CAR-Claudin 18.2[+] CD8[+] T cells, as well as in vivo tumor-bearing studies, have indicated that butyrate enhanced the killing function of CD8[+] T cells or CAR-Claudin 18.2[+] CD8[+] T cells against GC cells through G protein-coupled receptor 109A (GPR109A) and homologous domain protein homologous box (HOPX). Together, these data highlighted that the restoration of gut microbial butyrate enhanced CD8[+] T cell cytotoxicity via GPR109A/HOPX, thus inhibiting GC carcinogenesis, which suggests a novel theoretical foundation for GC management against GC.}, }
@article {pmid38319686, year = {2024}, author = {Martini, S and Zaccaria, T and Gasbarrini, A and Cammarota, G and Romagnoli, R and Ianiro, G}, title = {Fecal microbiota transplantation before liver transplant in patient colonized with New Delhi metallo-beta-lactamase: Are we ready for a sequential approach?.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {26}, number = {2}, pages = {e14248}, doi = {10.1111/tid.14248}, pmid = {38319686}, issn = {1399-3062}, support = {GR-2018-12365734//Ricerca Finalizzata Giovani Ricercatori 2018 of the Italian Ministry of Health/ ; FIS_00001711//Fondo Italiano per la Scienza 2021 of the Italian Ministry of University and Research/ ; //BIOMIS grant of the Italian Ministry of Research/ ; }, mesh = {Humans ; Fecal Microbiota Transplantation ; *Liver Transplantation/adverse effects ; beta-Lactamases/genetics ; *Klebsiella Infections ; Microbial Sensitivity Tests ; }, }
@article {pmid38317780, year = {2024}, author = {He, H and He, H and Mo, L and Yuan, Q and Xiao, C and Ma, Q and Yi, S and Zhou, T and You, Z and Zhang, J}, title = {Gut microbiota regulate stress resistance by influencing microglia-neuron interactions in the hippocampus.}, journal = {Brain, behavior, &amp; immunity - health}, volume = {36}, number = {}, pages = {100729}, pmid = {38317780}, issn = {2666-3546}, abstract = {Communication among the brain, gut and microbiota in the gut is known to affect the susceptibility to stress, but the mechanisms involved are unclear. Here we demonstrated that stress resistance in mice was associated with more abundant Lactobacillus and Akkermansia in the gut, but less abundant Bacteroides, Alloprevotella, Helicobacter, Lachnoclostridium, Blautia, Roseburia, Colidextibacter and Lachnospiraceae NK4A136. Stress-sensitive animals showed higher permeability and stronger immune responses in their colon, as well as higher levels of pro-inflammatory cytokines in serum. Their hippocampus also showed more extensive microglial activation, abnormal interactions between microglia and neurons, and lower synaptic plasticity. Transplanting fecal microbiota from stress-sensitive mice into naïve ones perturbed microglia-neuron interactions and impaired synaptic plasticity in the hippocampus, translating to more depression-like behavior after stress exposure. Conversely, transplanting fecal microbiota from stress-resistant mice into naïve ones protected microglia from activation and preserved synaptic plasticity in the hippocampus, leading to less depression-like behavior after stress exposure. These results suggested that gut microbiota may influence resilience to chronic psychological stress by regulating microglia-neuron interactions in the hippocampus.}, }
@article {pmid38317473, year = {2024}, author = {Chowdhury, M and Raj Chaudhary, N and Kaur, P and Goyal, A and Sahu, SK}, title = {Different Strategies Targeting Gut Microbiota for the Management of Several Disorders: A Sustainable Approach.}, journal = {Infectious disorders drug targets}, volume = {24}, number = {5}, pages = {e160124225675}, doi = {10.2174/0118715265267536231121095634}, pmid = {38317473}, issn = {2212-3989}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; *Prebiotics/administration &amp; dosage ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Synbiotics/administration &amp; dosage ; Gastrointestinal Tract/microbiology ; Obesity/microbiology/therapy ; }, abstract = {BACKGROUND: A potential limelight is flashed on the Gut Microbiota (GM) in the human body, which confers additional psychological as well as physiological attributes to health. Other than just occupying a wide portion of the gastrointestinal tract, it also plays numerous functions in the systems of the body. Gut Microbiota is largely responsible for a considerably vast array of conditions such as obesity, diabetes ,other metabolic disorders, and cardiovascular disorders. Strategies targeting the gut microbiota have been proposed as a promising approach for the management of these disorders.<br><br>OBJECTIVE: This review aims to summarize the different strategies targeting the gut microbiota for the management of several disorders and to highlight the importance of a sustainable approach.<br><br>METHODS: A comprehensive literature search was conducted using various databases between 2008 and 2022 that focused on the use of prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, dietary interventions, and antibiotics.<br><br>RESULTS: Different strategies targeting the gut microbiota for the management of several disorders were identified, including probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and dietary interventions. Modification in diet and lifestyle, allowing favorable microbiota growth in the stomach, intake of prebiotics and probiotics, and fecal microbiota transplantation are amongst the widely accepted recent approaches allowing the application of GM in the field of treatment.<br><br>CONCLUSION: Although considerable steps in enhancing and understanding the mechanism of treatment with the help of gut microbiota are under progress, much diversified and elaborate research must be conducted in order to enhance and implement the use of GM with high effectiveness.}, }
@article {pmid38317217, year = {2024}, author = {Xing, JH and Niu, TM and Zou, BS and Yang, GL and Shi, CW and Yan, QS and Sun, MJ and Yu, T and Zhang, SM and Feng, XZ and Fan, SH and Huang, HB and Wang, JH and Li, MH and Jiang, YL and Wang, JZ and Cao, X and Wang, N and Zeng, Y and Hu, JT and Zhang, D and Sun, WS and Yang, WT and Wang, CF}, title = {Gut microbiota-derived LCA mediates the protective effect of PEDV infection in piglets.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {20}, pmid = {38317217}, issn = {2049-2618}, support = {U21A20261&#xff0c; 721 32202819, 31941018, 31972696 and 32072888//National Natural Science Foundation of China/ ; CARS-35//China Agriculture Research System of MOF 722 and MARA/ ; 20190301042NY, YDZJ202102CXJD029, and 20210202102NC//Science and Technology Development Program of Jilin Province/ ; }, mesh = {Animals ; Swine ; *Gastrointestinal Microbiome ; *Porcine epidemic diarrhea virus ; *Coronavirus Infections/prevention &amp; control/veterinary ; *Swine Diseases/prevention &amp; control ; Disease Resistance ; }, abstract = {BACKGROUND: The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics.<br><br>RESULTS: Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids' deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8[+] CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8[+] CTLs to exert antiviral effects.<br><br>CONCLUSIONS: Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract.}, }
@article {pmid38316929, year = {2024}, author = {Ritz, NL and Draper, LA and Bastiaanssen, TFS and Turkington, CJR and Peterson, VL and van de Wouw, M and Vlckova, K and Fülling, C and Guzzetta, KE and Burokas, A and Harris, H and Dalmasso, M and Crispie, F and Cotter, PD and Shkoporov, AN and Moloney, GM and Dinan, TG and Hill, C and Cryan, JF}, title = {The gut virome is associated with stress-induced changes in behaviour and immune responses in mice.}, journal = {Nature microbiology}, volume = {9}, number = {2}, pages = {359-376}, pmid = {38316929}, issn = {2058-5276}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Mice ; Virome ; RNA, Ribosomal, 16S/genetics ; *Viruses/genetics ; *Microbiota ; *Bacteriophages/genetics ; Immunity ; }, abstract = {The microbiota-gut-brain axis has been shown to play an important role in the stress response, but previous work has focused primarily on the role of the bacteriome. The gut virome constitutes a major portion of the microbiome, with bacteriophages having the potential to remodel bacteriome structure and activity. Here we use a mouse model of chronic social stress, and employ 16S rRNA and whole metagenomic sequencing on faecal pellets to determine how the virome is modulated by and contributes to the effects of stress. We found that chronic stress led to behavioural, immune and bacteriome alterations in mice that were associated with changes in the bacteriophage class Caudoviricetes and unassigned viral taxa. To determine whether these changes were causally related to stress-associated behavioural or physiological outcomes, we conducted a faecal virome transplant from mice before stress and autochthonously transferred it to mice undergoing chronic social stress. The transfer of the faecal virome protected against stress-associated behaviour sequelae and restored stress-induced changes in select circulating immune cell populations, cytokine release, bacteriome alterations and gene expression in the amygdala. These data provide evidence that the virome plays a role in the modulation of the microbiota-gut-brain axis during stress, indicating that these viral populations should be considered when designing future microbiome-directed therapies.}, }
@article {pmid38316805, year = {2024}, author = {Prakash, A and Rubin, N and Staley, C and Onyeaghala, G and Wen, YF and Shaukat, A and Milne, G and Straka, RJ and Church, TR and Prizment, A}, title = {Effect of ginger supplementation on the fecal microbiome in subjects with prior colorectal adenoma.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {2988}, pmid = {38316805}, issn = {2045-2322}, mesh = {Adult ; Humans ; *Zingiber officinale ; RNA, Ribosomal, 16S/genetics/analysis ; *Colorectal Neoplasms/pathology ; Feces/chemistry ; *Microbiota ; *Adenoma/drug therapy ; Dietary Supplements ; }, abstract = {Ginger has been associated with a decreased incidence of colorectal cancer (CRC) through reduction in inflammatory pathways and inhibition of tumor growth. Recent pre-clinical models have implicated changes in the gut microbiome as a possible mediator of the ginger effect on CRC. We hypothesized that, in adults previously diagnosed with a colorectal adenoma, ginger supplementation would alter the fecal microbiome in the direction consistent with its CRC-inhibitory effect. Sixty-eight adults were randomized to take either ginger or placebo daily for 6 weeks, with a 6-week washout and longitudinal stool collection throughout. We performed 16S rRNA sequencing and evaluated changes in overall microbial diversity and the relative abundances of pre-specified CRC-associated taxa using mixed-effects logistic regression. Ginger supplementation showed no significant effect on microbial community structure through alpha or beta diversity. Of 10 pre-specified CRC-associated taxa, there were significant decreases in the relative abundances of the genera Akkermansia (p < 0.001), Bacteroides (p = 0.018), and Ruminococcus (p = 0.013) after 6-week treatment with ginger compared to placebo. Ginger supplementation led to decreased abundances of Akkermansia and Bacteroides, which suggests that ginger may have an inhibitory effect on CRC-associated taxa. Overall, ginger supplementation appears to have a limited effect on gut microbiome in patients with colorectal adenomas.}, }
@article {pmid38316265, year = {2024}, author = {Qu, L and Ma, X and Wang, F}, title = {The roles of gut microbiome and metabolites associated with skin photoaging in mice by intestinal flora sequencing and metabolomics.}, journal = {Life sciences}, volume = {341}, number = {}, pages = {122487}, doi = {10.1016/j.lfs.2024.122487}, pmid = {38316265}, issn = {1879-0631}, mesh = {Animals ; Mice ; *Skin Aging ; *Gastrointestinal Microbiome ; Matrix Metalloproteinase 1 ; RNA, Ribosomal, 16S/genetics ; Receptors, Tumor Necrosis Factor, Type I ; TNF Receptor-Associated Factor 2 ; Tandem Mass Spectrometry ; Ultraviolet Rays/adverse effects ; Metabolomics ; Arginine ; Citrulline ; Ornithine ; }, abstract = {Photoaging of skin, a chronic disease, can produce the appearance changes and cancer lesions of skin. Therefore, it is of great significance to investigate the mechanisms and explore effective methods to treat the disorder. Gut microbiota and intestinal metabolisms have critical roles in a variety of diseases. However, their roles on photoaging of skin were not well tested. In the present work, the results showed that compared with control group, the levels of MDA, SOD and CAT associated with oxidative stress, the levels of COL I, CER, and HA associated with skin function, and the mRNA levels of IL-1β, IL-6, TNF-α associated with inflammation after long-term exposure to ultraviolet radiation in mice were significantly changed. Skin pathological tissue was also seriously damaged. The protein levels of AQP3 and FLG were significantly decreased. Ultraviolet exposure also promoted skin photoaging by activating TNFR1/TRAF2-mediated MAPK pathway, in which the protein levels of P38/P-P38, c-FOS/P-c-FOS, MMP1, TNFR1 and TRAF2 were significantly increased in model mice compared with control group. In fecal microbiota transplantation (FMT) experiment, we found that the intestinal microbiome of control mice alleviated skin photoaging via adjusting the protein levels of P38/P-P38, c-FOS/P-c-FOS, MMP1, TNFR1 and TRAF2. 16S rRNA sequencing found that 1639 intestinal bacteria were found, in which 15 bacteria including norank_f_Ruminococcaceae, Lachnospirac -eae_NK4A136_group, Lachnoclostridium, etc., were significantly different at the genus level. Untargeted GC-TOF/MS and UHPLC-MS/MS metabolomics showed 72 and 188 metabolites including taurine, ornithine, L-arginine, L-histidine, sucrose with significant differences compared with control group. Then, amino acid targeting assay showed 10 amino acids including L-ornithine, L-arginine and L-citrulline with higher levels in control group compared with model group. In addition, we also found that the variation of Lachnoclostridium abundance may regulate L-arginine metabolism to affect skin photoaging. Some intestinal bacteria and metabolites including amino acids may be closely related to skin photoaging, which should provide new methods to treat skin photoaging in the future.}, }
@article {pmid38314929, year = {2024}, author = {Diaz-Marugan, L and Rutsch, A and Kaindl, AM and Ronchi, F}, title = {The impact of microbiota and ketogenic diet interventions in the management of drug-resistant epilepsy.}, journal = {Acta physiologica (Oxford, England)}, volume = {240}, number = {3}, pages = {e14104}, doi = {10.1111/apha.14104}, pmid = {38314929}, issn = {1748-1716}, support = {//Helmut Horten Foundation/ ; 2020/R-Single/029//FISM-Fondazione Italiana Sclerosi Multipla-Cod/ ; //Biostime Institute Nutrition &amp; Care (BINC)-Geneva/ ; //the Spanish Ministry of Universities (University of Barcelona)/ ; }, mesh = {Humans ; *Diet, Ketogenic ; Quality of Life ; *Microbiota ; Seizures ; *Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {AIM: Drug-resistant epilepsy (DRE) is a neurological disorder characterized by uncontrolled seizures. It affects between 10%-40% of the patients with epilepsy worldwide. Drug-resistant patients have been reported to have a different microbiota composition compared to drug-sensitive patients and healthy controls. Importantly, fecal microbiota transplantations (FMTs), probiotic and dietary interventions have been shown to be able to reduce seizure frequency and improve the quality of life in drug-resistant patients. The classic ketogenic diet (KD) and its modifications may reduce seizures in DRE in some patients, whereas in others they do not. The mechanisms mediating the dietary effects remain elusive, although it is known that gut microbes play an important role in transmitting dietary effects to the host. Indeed, specific commensal microbes differ even between responders and non-responders to KD treatment.<br><br>METHODS: In this narrative mini-review, we summarize what is known about the gut microbiota changes and ketogenic diets with special focus on patients with DRE.<br><br>RESULTS AND CONCLUSIONS: By highlighting unanswered questions and by suggesting future research directions, we map the route towards future improvement of successful DRE therapy.}, }
@article {pmid38314132, year = {2024}, author = {Yuan, XY and Chen, YS and Liu, Z}, title = {Relationship among Parkinson's disease, constipation, microbes, and microbiological therapy.}, journal = {World journal of gastroenterology}, volume = {30}, number = {3}, pages = {225-237}, pmid = {38314132}, issn = {2219-2840}, mesh = {Humans ; *Parkinson Disease/complications/therapy/microbiology ; Constipation/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson's disease (PD), a prevalent non-motor symptom contributing significantly to patients' morbidity. A marked alteration in the gut microbiota, predominantly an increase in the abundance of Proteobacteria and Bacteroidetes, is observed in PD-related constipation. Conventional treatments, although safe, have failed to effectively alleviate symptoms, thereby necessitating the development of novel therapeutic strategies. Microbiological interventions such as prebiotics, probiotics, and fecal microbiota transplantation (FMT) hold therapeutic potential. While prebiotics improve bowel movements, probiotics are effective in enhancing stool consistency and alleviating abdominal discomfort. FMT shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with PD. Despite promising developments, the causal relationship between changes in gut microbiota and PD-related constipation remains elusive, highlighting the need for further research in this expanding field.}, }
@article {pmid38313244, year = {2024}, author = {Shah, YR and Ali, H and Tiwari, A and Guevara-Lazo, D and Nombera-Aznaran, N and Pinnam, BSM and Gangwani, MK and Gopakumar, H and Sohail, AH and Kanumilli, S and Calderon-Martinez, E and Krishnamoorthy, G and Thakral, N and Dahiya, DS}, title = {Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions.}, journal = {World journal of hepatology}, volume = {16}, number = {1}, pages = {17-32}, pmid = {38313244}, issn = {1948-5182}, abstract = {Fecal microbiota transplantation (FMT) offers a potential treatment avenue for hepatic encephalopathy (HE) by leveraging beneficial bacterial displacement to restore a balanced gut microbiome. The prevalence of HE varies with liver disease severity and comorbidities. HE pathogenesis involves ammonia toxicity, gut-brain communication disruption, and inflammation. FMT aims to restore gut microbiota balance, addressing these factors. FMT's efficacy has been explored in various conditions, including HE. Studies suggest that FMT can modulate gut microbiota, reduce ammonia levels, and alleviate inflammation. FMT has shown promise in alcohol-associated, hepatitis B and C-associated, and non-alcoholic fatty liver disease. Benefits include improved liver function, cognitive function, and the slowing of disease progression. However, larger, controlled studies are needed to validate its effectiveness in these contexts. Studies have shown cognitive improvements through FMT, with potential benefits in cirrhotic patients. Notably, trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care. Although evidence is promising, challenges remain: Limited patient numbers, varied dosages, administration routes, and donor profiles. Further large-scale, controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy. While FMT holds potential for HE management, ongoing research is needed to address these challenges, optimize protocols, and expand its availability as a therapeutic option for diverse hepatic conditions.}, }
@article {pmid38312240, year = {2024}, author = {Huang, H and Jiang, J and Wang, X and Jiang, K and Cao, H}, title = {Exposure to prescribed medication in early life and impacts on gut microbiota and disease development.}, journal = {EClinicalMedicine}, volume = {68}, number = {}, pages = {102428}, pmid = {38312240}, issn = {2589-5370}, abstract = {The gut microbiota during early life plays a crucial role in infant development. This microbial-host interaction is also essential for metabolism, immunity, and overall human health in later life. Early-life pharmaceutical exposure, mainly referring to exposure during pregnancy, childbirth, and infancy, may change the structure and function of gut microbiota and affect later human health. In this Review, we describe how healthy gut microbiota is established in early life. We summarise the commonly prescribed medications during early life, including antibiotics, acid suppressant medications and other medications such as antidepressants, analgesics and steroid hormones, and discuss how these medication-induced changes in gut microbiota are involved in the pathological process of diseases, including infections, inflammatory bowel disease, metabolic diseases, allergic diseases and neurodevelopmental disorders. Finally, we review some critical methods such as dietary therapy, probiotics, prebiotics, faecal microbiota transplantation, genetically engineered phages, and vagus nerve stimulation in early life, aiming to provide a new strategy for the prevention of adverse health outcomes caused by prescribed medications exposure in early life.}, }
@article {pmid38309391, year = {2024}, author = {Zheng, YZ and Chen, QR and Yang, HM and Zhao, JA and Ren, LZ and Wu, YQ and Long, YL and Li, TM and Yu, Y}, title = {Modulation of gut microbiota by crude mulberry polysaccharide attenuates knee osteoarthritis progression in rats.}, journal = {International journal of biological macromolecules}, volume = {262}, number = {Pt 2}, pages = {129936}, doi = {10.1016/j.ijbiomac.2024.129936}, pmid = {38309391}, issn = {1879-0003}, mesh = {Rats ; Animals ; *Osteoarthritis, Knee/drug therapy ; *Gastrointestinal Microbiome ; Fruit ; *Morus ; Polysaccharides/pharmacology/therapeutic use ; }, abstract = {Mulberry (Morus alba L.), a kind of common fruits widely cultivated worldwide, has been proven various biological activities. However, its potential role in the progression of knee osteoarthritis (KOA) remains unclear. This study aims to investigate the potential protective effects of crude polysaccharide extracted from mulberry fruit, referred to as a complex blend of polysaccharides and other unidentified extracted impurities, on KOA progression. The KOA rats were established by injection of 1 mg sodium monoiodoacetate into knee, and administrated with crude mulberry polysaccharide (Mup) by gastric gavage for 4 weeks. Furthermore, intestinal bacteria clearance assay (IBCA) and fecal microbiota transplantation were conducted for the evaluation of the effect of gut microbiota (GM) on KOA. Our findings demonstrated that Mup, particularly at a dosage of 200 mg/kg, effectively improved abnormal gait patterns, reduced the level of inflammation, mitigated subchondral bone loss, restored compromised joint surfaces, alleviated cartilage destruction, and positively modulated the dysregulated profile of GM in KOA rats. Moreover, IBCA compromised the protective effects of Mup, while transplantation of fecal bacteria from Mup-treated rats facilitated KOA recovery. Collectively, our study suggested that Mup had the potential to ameliorate the progression of KOA, potentially through its modulation of GM profile.}, }
@article {pmid38309340, year = {2024}, author = {Yu, K and Song, Y and Wang, N and Yu, X and Sun, T and Yu, H and Ruan, Z and Qiu, Y}, title = {Exposure of Danio rerio to environmental sulfamethoxazole may contribute to neurobehavioral abnormalities via gut microbiome disturbance.}, journal = {The Science of the total environment}, volume = {918}, number = {}, pages = {170546}, doi = {10.1016/j.scitotenv.2024.170546}, pmid = {38309340}, issn = {1879-1026}, mesh = {Animals ; *Gastrointestinal Microbiome ; Zebrafish/genetics ; Sulfamethoxazole/toxicity ; *Microbiota ; Metagenome ; }, abstract = {The neurotoxic effects and mechanisms of low-dose and long-term sulfamethoxazole (SMZ) exposure remain unknown. This study exposed zebrafish to environmental SMZ concentrations and observed behavioral outcomes. SMZ exposure increased hyperactivity and altered the transcript levels of 17 genes associated with neurological function. It impaired intestinal function by reducing the number of intestinal goblet cells and lipid content. Metabolomic results indicated that the contents of several lipids and amino acids in the gut were altered, which might affect the expression levels of neurological function-related genes. Metagenomic results demonstrated that SMZ exposure substantially altered the composition of the gut microbiome. Zebrafish receiving a transplanted fecal microbiome from the SMZ group were also found to exhibit abnormal behavior, suggesting that the gut microbiome is an important target for SMZ exposure-induced neurobehavioral abnormalities. Multi-omics correlation analysis revealed that gut micrometabolic function was related to differential gut metabolite levels, which may affect neurological function through the gut-brain-axis. Reduced abundance of Lefsonia and Microbacterium was strongly correlated with intestinal metabolic function and may be the key bacterial genera in neurobehavioral changes. This study confirms for the first time that SMZ-induced neurotoxicity in zebrafish is closely mediated by alterations in the gut microbiome.}, }
@article {pmid38306142, year = {2024}, author = {Natarelli, N and Aflatooni, S and Boby, A and Krenitsky, A and Grichnik, J}, title = {The Gastrointestinal Microbiome and Immune Checkpoint Inhibitors: A Review of Human Interventional Studies Among Melanoma Patients.}, journal = {Journal of drugs in dermatology : JDD}, volume = {23}, number = {2}, pages = {78-84}, doi = {10.36849/JDD.7674}, pmid = {38306142}, issn = {1545-9616}, mesh = {Humans ; *Colitis ; *Gastrointestinal Microbiome ; Immune Checkpoint Inhibitors/adverse effects ; *Melanoma/therapy ; Remission Induction ; }, abstract = {Immune checkpoint inhibitors (ICI) are widely utilized for the treatment of malignant melanoma. Interestingly, gastrointestinal microbiome composition has emerged as a predictive biomarker of immunotherapy outcomes. This review seeks to assess the effect of microbiota-modulatory interventions on the clinical and immunological response of metastatic melanoma treated with ICIs. A systematic search was performed to retrieve studies and cases involving any microbiota-modulating intervention. Three studies assessed the effect of fecal microbiota transplantation (FMT) on ICI efficacy, and one case report assessed its effect on clearance of ICI-associated colitis. Overall, 37.5% of melanoma patients who had been previously refractory to ICI immunotherapy demonstrated complete or partial response following FMT and subsequent immunotherapy. 65% of immunotherapy-na&amp;iuml;ve melanoma patients demonstrated an objective response. No severe FMT-associated adverse events were reported, and FMT depicted efficacy in the remission of ICI-associated colitis. The results suggest that FMT may be a safe and moderately effective microbiota-modulating intervention to improve the efficacy of therapy in ICI-treated melanoma patients. Large, randomized, controlled trials are needed to determine optimal FMT donors and assess other microbiota-modulating interventions, such as pre- and probiotics, in melanoma patients.&amp;nbsp; J Drugs Dermatol. 2024;23(2):78-84.&amp;nbsp; &amp;nbsp;&amp;nbsp; doi:10.36849/JDD.7674.}, }
@article {pmid39093178, year = {2023}, author = {Von Muhlenbrock, C and Núñez, P and Espinoza, R and Quera, R}, title = {[Update in diagnosis and management of Clostridioides difficile].}, journal = {Revista medica de Chile}, volume = {151}, number = {7}, pages = {887-898}, doi = {10.4067/s0034-98872023000700887}, pmid = {39093178}, issn = {0717-6163}, mesh = {Humans ; *Clostridium Infections/diagnosis/therapy ; *Clostridioides difficile/pathogenicity ; Anti-Bacterial Agents/therapeutic use ; Risk Factors ; Practice Guidelines as Topic ; Fecal Microbiota Transplantation ; Chile/epidemiology ; }, abstract = {Clostridioides difficile (C. difficile) is one of the leading causes of infection associated with health care with high morbidity and mortality, especially among hospitalized older adults. The increase in the use of antibiotics has been associated with a higher number of cases and greater virulence. Its clinical presentation ranges from asymptomatic carriers to toxic megacolon. Studies with stool tests (glutamate dehydrogenase, toxins A and B, and nuclear acid amplification techniques) should be considered in these cases. Fidaxomicin, fecal microbiota transplant, and new therapies such as monoclonal antibodies have been incorporated into the therapeutic arsenal, with a higher level of evidence. Nevertheless, the severity, patient comorbidity, recurrence risk factors, and the economic cost of each therapeutic option must be considered. This review aims to update the last guidelines proposed by the Chilean Societies of Gastroenterology and Infectious Diseases published in 2016, providing the latest recommendations regarding prevention, diagnosis, and treatment of C. difficile infection.}, }
@article {pmid39295910, year = {2023}, author = {Sehn Hilgert, S and Dias, DPM}, title = {The intestinal microbiota as an ally in the treatment of Alzheimer's disease.}, journal = {Gut microbiome (Cambridge, England)}, volume = {4}, number = {}, pages = {e9}, pmid = {39295910}, issn = {2632-2897}, abstract = {The evolution of the understanding of the intestinal microbiota and its influence on our organism leverages it as a potential protagonist in therapies aimed at diseases that affect not only the intestine but also neural pathways and the central nervous system itself. This study, developed from a thorough systematic review, sought to demonstrate the influence of the intervention on the intestinal microbiota in subjects with Alzheimer's disease. Clinical trials using different classes of probiotics have depicted noteworthy remission of symptoms, whose measurement was performed based on screenings and scores applied before, during, and after the period of probiotics use, allowing the observation of changes in functionality and symptomatology of patients. On the other hand, faecal microbiota transplantation requires further validation through clinical trials, even though it has already been reported in case studies as promising from the symptomatology point of view. The current compilation of studies made it possible to demonstrate the potential influence of the intestinal microbiota on Alzheimer's pathology. However, new clinical studies with a larger number of participants are needed to obtain further clarification on pathophysiological correlations.}, }
@article {pmid39130120, year = {2023}, author = {Kahan, T and Chandan, S and Khan, SR and Deliwala, S and Chang, S and Axelrad, J and Shaukat, A}, title = {Safety and Efficacy of Fecal Microbiota Transplant in Chronic Pouchitis-A Systematic Review With Meta-Analysis.}, journal = {Gastro hep advances}, volume = {2}, number = {6}, pages = {843-852}, pmid = {39130120}, issn = {2772-5723}, support = {K23 DK124570/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND AND AIMS: Pouchitis is the most common long-term complication after ileal-pouch anal anastomosis in patients with ulcerative colitis. We conducted a systematic review and meta-analysis evaluating the safety and efficacy of fecal microbiota transplant (FMT) in chronic antibiotic dependent and refractory pouchitis.<br><br>METHODS: Multiple databases were searched through April 2022 for studies that reported the efficacy and safety of FMT in patients with chronic pouchitis. Meta-analysis using random effects model was performed to calculate pooled rates.<br><br>RESULTS: Eight studies with a total of 89 patients were included in our review, with 74 patients having received FMT and 15 patients having received placebo. The mean age ranged from 32.6 to 51.5 years. In patients that received FMT, the pooled rates of overall remission was (Pouchitis Disease Activity Index score < 7) 22% (95% CI, 9%-43%; I[2], 29%), clinical remission was 20% (95% CI, 6%-49%; I[2], 25%), clinical response rate was 42% (95% CI, 30%-54%; I[2], 7%), and the relapse rate 60% (95% CI, 40%-77%, I[2] 16%) over the mean follow up of 4.67 months (range 1-12 months). The pooled proportion of patients with adverse events was 54% (95% CI, 21%-84%; I[2], 73%). There were no serious adverse events or deaths.<br><br>CONCLUSION: In patients with chronic pouchitis, FMT is safe though there are mixed results in terms of its long-term efficacy. Future Randomized Controlled Trials with larger sample sizes and greater standardization in terms of preparation, delivery, and length of treatment of FMT are needed to determine efficacy.}, }
@article {pmid38868343, year = {2023}, author = {Liu, J and Ding, M and Bai, J and Luo, R and Liu, R and Qu, J and Li, X}, title = {Decoding the role of immune T cells: A new territory for improvement of metabolic-associated fatty liver disease.}, journal = {iMeta}, volume = {2}, number = {1}, pages = {e76}, pmid = {38868343}, issn = {2770-596X}, abstract = {Metabolic-associated fatty liver disease (MAFLD) is a new emerging concept and is associated with metabolic dysfunction, generally replacing the name of nonalcoholic fatty liver disease (NAFLD) due to heterogeneous liver condition and inaccuracies in definition. The prevalence of MAFLD is rising by year due to dietary changes, metabolic disorders, and no approved therapy, affecting a quarter of the global population and representing a major economic problem that burdens healthcare systems. Currently, in addition to the common causative factors like insulin resistance, oxidative stress, and lipotoxicity, the role of immune cells, especially T cells, played in MAFLD is increasingly being emphasized by global scholars. Based on the diverse classification and pathophysiological effects of immune T cells, we comprehensively analyzed their bidirectional regulatory effects on the hepatic inflammatory microenvironment and MAFLD progression. This interaction between MAFLD and T cells was also associated with hepatic-intestinal immune crosstalk and gut microbiota homeostasis. Moreover, we pointed out several T-cell-based therapeutic approaches including but not limited to adoptive transfer of T cells, fecal microbiota transplantation, and drug therapy, especially for natural products and Chinese herbal prescriptions. Overall, this study contributes to a better understanding of the important role of T cells played in MAFLD progression and corresponding therapeutic options and provides a potential reference for further drug development.}, }
@article {pmid38868341, year = {2023}, author = {Wang, XW and Wu, L and Dai, L and Yin, X and Zhang, T and Weiss, ST and Liu, YY}, title = {Ecological dynamics imposes fundamental challenges in community-based microbial source tracking.}, journal = {iMeta}, volume = {2}, number = {1}, pages = {e75}, pmid = {38868341}, issn = {2770-596X}, support = {U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; RF1 AG067744/AG/NIA NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, abstract = {Quantifying the contributions of possible environmental sources ("sources") to a specific microbial community ("sink") is a classical problem in microbiology known as microbial source tracking (MST). Solving the MST problem will not only help us understand how microbial communities were formed, but also have far-reaching applications in pollution control, public health, and forensics. MST methods generally fall into two categories: target-based methods (focusing on the detection of source-specific indicator species or chemicals); and community-based methods (using community structure to measure similarity between sink samples and potential source environments). As next-generation sequencing becomes a standard community-assessment method in microbiology, numerous community-based computational methods, referred to as MST solvers hereafter have been developed and applied to various real datasets to demonstrate their utility across different contexts. Yet, those MST solvers do not consider microbial interactions and priority effects in microbial communities. Here, we revisit the performance of several representative MST solvers. We show compelling evidence that solving the MST problem using existing MST solvers is impractical when ecological dynamics plays a role in community assembly. In particular, we clearly demonstrate that the presence of either microbial interactions or priority effects will render the MST problem mathematically unsolvable for MST solvers. We further analyze data from fecal microbiota transplantation studies, finding that the state-of-the-art MST solvers fail to identify donors for most of the recipients. Finally, we perform community coalescence experiments to demonstrate that the state-of-the-art MST solvers fail to identify the sources for most of the sinks. Our findings suggest that ecological dynamics imposes fundamental challenges in MST. Interpretation of results of existing MST solvers should be done cautiously.}, }
@article {pmid39165756, year = {2023}, author = {Hosseini, PSK and Wang, B and Luan, Y and Sun, F and Michail, S}, title = {Gut metabolomic profiles in paediatric ulcerative colitis patients prior to and after receiving faecal microbiota transplants.}, journal = {Gut microbiome (Cambridge, England)}, volume = {4}, number = {}, pages = {}, pmid = {39165756}, issn = {2632-2897}, support = {R01 HD081197/HD/NICHD NIH HHS/United States ; UL1 TR000130/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; }, abstract = {Ulcerative colitis (UC) is an immune-mediated inflammation of the colonic mucosa. Gut microbiota dysbiosis may play a significant role in disease pathogenesis by causing shifts in metabolomic profiles within the gut. To identify differences and trends in the metabolomic profile of paediatric UC patients pre- and post-faecal microbiota transplants (FMT). Forty-six paediatric patients with mild-to-moderate UC and 30 healthy paediatric patients were enrolled in this study. Baseline stool samples were collected prior to FMT initiation and at months 1, 3, 6, and 12 post-FMT. Pediatric Ulcerative Colitis Activity Index (PUCAI) scores were calculated at baseline and months 1, 3, 6, and 12 after FMT. The average Bray-Curtis dissimilarities to healthy subjects decreased after FMT. In principal coordinate analysis plots, UC patients' centroids drew nearer to healthy individuals. The variance explained by phenotype (Healthy versus UC) reduced and remained significant. From 1 to 3 months after FMT, PUCAI trends were statistically significant and decreasing. PUCAI scores remain flat starting 6 months after FMT. This study concludes that paediatric UC patients have a significantly different baseline metabolite profile than healthy controls. Although being time limited, FMT significantly altered these metabolite profiles and shifted them towards that of healthy controls.}, }
@article {pmid38867907, year = {2022}, author = {Ma, Y and Ke, D and Li, D and Zhang, Q}, title = {Donors' experiences and attitudes of fecal microbiota transplantation: An empirical bioethics study from China.}, journal = {iMeta}, volume = {1}, number = {4}, pages = {e62}, pmid = {38867907}, issn = {2770-596X}, abstract = {Donor participation is a critical part of ensuring the development of human microbiome research and the clinical application of fecal microbiota transplantation (FMT). Most FMT donors are still not sufficiently aware of the risks associated with the act of donating gut microbiota, especially the risk of data privacy disclosure. Enhanced awareness of the moral responsibility of the researchers and ethical oversight by ethics committees are needed.}, }
@article {pmid39295774, year = {2022}, author = {Iribarren, C and Maasfeh, L and Öhman, L and Simrén, M}, title = {Modulating the gut microenvironment as a treatment strategy for irritable bowel syndrome: a narrative review.}, journal = {Gut microbiome (Cambridge, England)}, volume = {3}, number = {}, pages = {e7}, pmid = {39295774}, issn = {2632-2897}, abstract = {Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction with a complex pathophysiology. Growing evidence suggests that alterations of the gut microenvironment, including microbiota composition and function, may be involved in symptom generation. Therefore, attempts to modulate the gut microenvironment have provided promising results as an indirect approach for IBS management. Antibiotics, probiotics, prebiotics, food and faecal microbiota transplantation are the main strategies for alleviating IBS symptom severity by modulating gut microbiota composition and function (eg. metabolism), gut barrier integrity and immune activity, although with varying efficacy. In this narrative review, we aim to provide an overview of the current approaches targeting the gut microenvironment in order to indirectly manage IBS symptoms.}, }
@article {pmid38868710, year = {2022}, author = {Hu, H and Tan, Y and Li, C and Chen, J and Kou, Y and Xu, ZZ and Liu, YY and Tan, Y and Dai, L}, title = {StrainPanDA: Linked reconstruction of strain composition and gene content profiles via pangenome-based decomposition of metagenomic data.}, journal = {iMeta}, volume = {1}, number = {3}, pages = {e41}, pmid = {38868710}, issn = {2770-596X}, abstract = {Microbial strains of variable functional capacities coexist in microbiomes. Current bioinformatics methods of strain analysis cannot provide the direct linkage between strain composition and their gene contents from metagenomic data. Here we present Strain-level Pangenome Decomposition Analysis (StrainPanDA), a novel method that uses the pangenome coverage profile of multiple metagenomic samples to simultaneously reconstruct the composition and gene content variation of coexisting strains in microbial communities. We systematically validate the accuracy and robustness of StrainPanDA using synthetic data sets. To demonstrate the power of gene-centric strain profiling, we then apply StrainPanDA to analyze the gut microbiome samples of infants, as well as patients treated with fecal microbiota transplantation. We show that the linked reconstruction of strain composition and gene content profiles is critical for understanding the relationship between microbial adaptation and strain-specific functions (e.g., nutrient utilization and pathogenicity). Finally, StrainPanDA has minimal requirements for computing resources and can be scaled to process multiple species in a community in parallel. In short, StrainPanDA can be applied to metagenomic data sets to detect the association between molecular functions and microbial/host phenotypes to formulate testable hypotheses and gain novel biological insights at the strain or subspecies level.}, }
@article {pmid39131119, year = {2022}, author = {Watts, AE and Sninsky, JA and Richey, MM and Donovan, K and Dougherty, MK and McGill, SK}, title = {Family Stool Donation Predicts Failure of Fecal Microbiota Transplant for Clostridioides difficile Infection.}, journal = {Gastro hep advances}, volume = {1}, number = {2}, pages = {141-146}, pmid = {39131119}, issn = {2772-5723}, support = {T32 DK007634/DK/NIDDK NIH HHS/United States ; U01 TR002398/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplant (FMT) via colonoscopy is highly effective treatment for Clostridioides difficile infection (CDI). We aimed to determine baseline patient characteristics that predict failure to respond to colonoscopy-based FMT.<br><br>METHODS: We evaluated adult patients who received FMT for CDI not responding to standard therapies at a single tertiary center between 2014 and 2018 in this retrospective cohort study. We defined clinical success as formed stool or C difficile-negative diarrhea at 2 months after FMT. If patients required a second FMT, follow-up was extended 2 months after repeat infusion. We performed multivariate logistic regression and a random forest model to identify variables predictive of response to FMT.<br><br>RESULTS: Clinical success was attained in 87.3% of 103 patients who underwent FMT for CDI. In the multivariate model, the odds of FMT failure for family donation compared with stool bank were odds ratio 4.13 (1.00-7.01 P&#xa0;= .049). Diarrhea while taking anti-CDI antibiotics was common (37.8% of patients) and did not predict failure (odds ratio 0.64, 0.19-2.11 P&#xa0;= .46) in the univariate model. A machine learning model to predict response using clinical factors only achieved a sensitivity of 70%, specificity of 77%, and negative predictive value of 96%.<br><br>CONCLUSION: Colonoscopy-based FMT was highly effective for CDI, even in a population where immunosuppression and proton pump inhibitor use were common. Family stool donation was associated with FMT failure, compared with the use of a stool bank. The study suggests that the use of a stool bank may not only improve access to FMT but also its efficacy.}, }
@article {pmid38624958, year = {2021}, author = {Malhotra, S and Mohandas, S}, title = {Updates and Opinions in Diagnosis and Treatment of Clostridiodes difficile in Pediatrics.}, journal = {Current treatment options in pediatrics}, volume = {7}, number = {4}, pages = {203-216}, pmid = {38624958}, issn = {2198-6088}, abstract = {PURPOSE OF REVIEW: Clostridiodes difficile infection (CDI) has unique challenges for diagnosis and treatment in pediatrics. Though new antibiotics and biologics are being approved or developed for adults, most of the pediatric therapies still rely on multiple or extended antibiotic courses. This review aims to highlight emerging evidence and our clinical experience with CDI in children and can help inform readers' approach to pediatric CDI.<br><br>RECENT FINDINGS: Use of fidaxomicin for CDI in pediatrics has been shown to be to be non-inferior to vancomycin and is associated with higher global cure rates and decreased risk of recurrence. Fecal microbiota transplant is a successful emerging therapy with cure rates of up to 90%, though safety alerts should be noted. Diagnostic laboratory testing for C. difficile remains a challenge as it still cannot definitively distinguish between colonization and true infection, and this is particularly relevant to pediatric patients as they have the highest rates of colonization.<br><br>SUMMARY: The diagnosis and treatment of C. difficile infection in pediatrics remain challenging and recommendations lag behind advances made in the adult field. Recent data suggests that use of fidaxomicin both as treatment of first episode or recurrences may be beneficial in pediatrics just as in adults. At an experienced center, FMT is associated with high cure rates. Bezlotuxumab a monoclonal antibody to toxin B that is already recommended for use in adults is being studied in children and should be available for clinical use soon. Oral vancomycin prophylaxis is also an emerging strategy for high-risk patients. Finally, a possible vaccine may be on the horizon for pediatrics.}, }
@article {pmid38305096, year = {2024}, author = {Linnehan, BK and Kodera, SM and Allard, SM and Brodie, EC and Allaband, C and Knight, R and Lutz, HL and Carroll, MC and Meegan, JM and Jensen, ED and Gilbert, JA}, title = {Evaluation of the safety and efficacy of fecal microbiota transplantations in bottlenose dolphins (Tursiops truncatus) using metagenomic sequencing.}, journal = {Journal of applied microbiology}, volume = {135}, number = {2}, pages = {}, pmid = {38305096}, issn = {1365-2672}, support = {S10 OD026929/OD/NIH HHS/United States ; #S10 OD026929/NH/NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation/methods ; *Bottle-Nosed Dolphin ; Prospective Studies ; Feces ; *Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {AIMS: Gastrointestinal disease is a leading cause of morbidity in bottlenose dolphins (Tursiops truncatus) under managed care. Fecal microbiota transplantation (FMT) holds promise as a therapeutic tool to restore gut microbiota without antibiotic use. This prospective clinical study aimed to develop a screening protocol for FMT donors to ensure safety, determine an effective FMT administration protocol for managed dolphins, and evaluate the efficacy of FMTs in four recipient dolphins.<br><br>METHODS AND RESULTS: Comprehensive health monitoring was performed on donor and recipient dolphins. Fecal samples were collected before, during, and after FMT therapy. Screening of donor and recipient fecal samples was accomplished by in-house and reference lab diagnostic tests. Shotgun metagenomics was used for sequencing. Following FMT treatment, all four recipient communities experienced engraftment of novel microbial species from donor communities. Engraftment coincided with resolution of clinical signs and a sustained increase in alpha diversity.<br><br>CONCLUSION: The donor screening protocol proved to be safe in this study and no adverse effects were observed in four recipient dolphins. Treatment coincided with improvement in clinical signs.}, }
@article {pmid38302438, year = {2024}, author = {Eberhart, T and Stanley, FU and Ricci, L and Chirico, T and Ferrarese, R and Sisti, S and Scagliola, A and Baj, A and Badurek, S and Sommer, A and Culp-Hill, R and Dzieciatkowska, M and Shokry, E and Sumpton, D and D'Alessandro, A and Clementi, N and Mancini, N and Cardaci, S}, title = {ACOD1 deficiency offers protection in a mouse model of diet-induced obesity by maintaining a healthy gut microbiota.}, journal = {Cell death &amp; disease}, volume = {15}, number = {2}, pages = {105}, pmid = {38302438}, issn = {2041-4889}, support = {Start-Up 2017 - ID. 20464 project//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; GR-2018-12365954//Ministero della Salute (Ministry of Health, Italy)/ ; }, mesh = {Animals ; Mice ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Obesity/metabolism ; *Succinates ; }, abstract = {Aconitate decarboxylase 1 (ACOD1) is the enzyme synthesizing itaconate, an immuno-regulatory metabolite tuning host-pathogen interactions. Such functions are achieved by affecting metabolic pathways regulating inflammation and microbe survival. However, at the whole-body level, metabolic roles of itaconate remain largely unresolved. By using multiomics-integrated approaches, here we show that ACOD1 responds to high-fat diet consumption in mice by promoting gut microbiota alterations supporting metabolic disease. Genetic disruption of itaconate biosynthesis protects mice against obesity, alterations in glucose homeostasis and liver metabolic dysfunctions by decreasing meta-inflammatory responses to dietary lipid overload. Mechanistically, fecal metagenomics and microbiota transplantation experiments demonstrate such effects are dependent on an amelioration of the intestinal ecosystem composition, skewed by high-fat diet feeding towards obesogenic phenotype. In particular, unbiased fecal microbiota profiling and axenic culture experiments point towards a primary role for itaconate in inhibiting growth of Bacteroidaceae and Bacteroides, family and genus of Bacteroidetes phylum, the major gut microbial taxon associated with metabolic health. Specularly to the effects imposed by Acod1 deficiency on fecal microbiota, oral itaconate consumption enhances diet-induced gut dysbiosis and associated obesogenic responses in mice. Unveiling an unrecognized role of itaconate, either endogenously produced or exogenously administered, in supporting microbiota alterations underlying diet-induced obesity in mice, our study points ACOD1 as a target against inflammatory consequences of overnutrition.}, }
@article {pmid38301301, year = {2024}, author = {Yan, M and Zhao, Y and Man, S and Dai, Y and Ma, L and Gao, W}, title = {Diosgenin as a substitute for cholesterol alleviates NAFLD by affecting CYP7A1 and NPC1L1-related pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {125}, number = {}, pages = {155299}, doi = {10.1016/j.phymed.2023.155299}, pmid = {38301301}, issn = {1618-095X}, mesh = {Mice ; Animals ; *Non-alcoholic Fatty Liver Disease/drug therapy/pathology ; *Diosgenin/pharmacology/metabolism ; Molecular Docking Simulation ; Liver ; Cholesterol/metabolism ; *Hypercholesterolemia/drug therapy ; Lipid Metabolism ; Diet, High-Fat/adverse effects ; }, abstract = {BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) rapidly becomes the leading cause of end-stage liver disease or liver transplantation. Nowadays, there has no approved drug for NAFLD treatment. Diosgenin as the structural analogue of cholesterol attenuates hypercholesterolemia by inhibiting cholesterol metabolism, which is an important pathogenesis in NAFLD progression. However, there has been no few report concerning its effects on NAFLD so far.<br><br>METHODS: Using a high-fat diet &amp; 10% fructose-feeding mice, we evaluated the anti-NAFLD effects of diosgenin. Transcriptome sequencing, LC/MS analysis, molecular docking simulation, molecular dynamics simulations and Luci fluorescent reporter gene analysis were used to evaluate pathways related to cholesterol metabolism.<br><br>RESULTS: Diosgenin treatment ameliorated hepatic dysfunction and inhibited NAFLD formation including lipid accumulation, inflammation aggregation and fibrosis formation through regulating cholesterol metabolism. For the first time, diosgenin was structurally similar to cholesterol, down-regulated expression of CYP7A1 and regulated cholesterol metabolism in the liver (p < 0.01) and further affecting bile acids like CDCA, CA and TCA in the liver and feces. Besides, diosgenin decreased expression of NPC1L1 and suppressed cholesterol transport (p < 0.05). Molecular docking and molecular dynamics further proved that diosgenin was more strongly bound to CYP7A1. Luci fluorescent reporter gene analysis revealed that diosgenin concentration-dependently inhibited the enzymes activity of CYP7A1.<br><br>CONCLUSION: Our findings demonstrated that diosgenin was identified as a specific regulator of cholesterol metabolism, which pave way for the design of novel clinical therapeutic strategies.}, }
@article {pmid38300802, year = {2024}, author = {Kirk, D and Costeira, R and Visconti, A and Khan Mirzaei, M and Deng, L and Valdes, AM and Menni, C}, title = {Bacteriophages, gut bacteria, and microbial pathways interplay in cardiometabolic health.}, journal = {Cell reports}, volume = {43}, number = {2}, pages = {113728}, pmid = {38300802}, issn = {2211-1247}, mesh = {Humans ; *Bacteriophages ; *Gastrointestinal Microbiome ; Bacteria ; Fecal Microbiota Transplantation ; *Cardiovascular Diseases/therapy ; }, abstract = {Cardiometabolic diseases are leading causes of mortality in Western countries. Well-established risk factors include host genetics, lifestyle, diet, and the gut microbiome. Moreover, gut bacterial communities and their activities can be altered by bacteriophages (also known simply as phages), bacteria-infecting viruses, making these biological entities key regulators of human cardiometabolic health. The manipulation of bacterial populations by phages enables the possibility of using phages in the treatment of cardiometabolic diseases through phage therapy and fecal viral transplants. First, however, a deeper understanding of the role of the phageome in cardiometabolic diseases is required. In this review, we first introduce the phageome as a component of the gut microbiome and discuss fecal viral transplants and phage therapy in relation to cardiometabolic diseases. We then summarize the current state of phageome research in cardiometabolic diseases and propose how the phageome might indirectly influence cardiometabolic health through gut bacteria and their metabolites.}, }
@article {pmid38299844, year = {2024}, author = {Zhang, Z and Huang, J and Li, C and Zhao, Z and Cui, Y and Yuan, X and Wang, X and Liu, Y and Zhou, Y and Zhu, Z}, title = {The gut microbiota contributes to the infection of bovine viral diarrhea virus in mice.}, journal = {Journal of virology}, volume = {98}, number = {2}, pages = {e0203523}, pmid = {38299844}, issn = {1098-5514}, support = {YQ2023C036//Natural Science Foundation of the Heilongjiang Province of China/ ; XYB202014//Heilongjiang Bayi Agricultural University Talent Research Start-up Fund/ ; 32302949//MOST | National Natural Science Foundation of China (NSFC)/ ; 2023ZXJ02B03//Heilongjiang Province's "Jie Bang Gua Shuai" Science and Technology Research Project/ ; }, mesh = {Animals ; Cattle ; Mice ; *Bovine Virus Diarrhea-Mucosal Disease/complications/microbiology/therapy/virology ; Butyrates/metabolism ; Caspase 3/metabolism ; Caspase 9/metabolism ; Diarrhea ; *Diarrhea Viruses, Bovine Viral/pathogenicity/physiology ; Dysbiosis/complications/microbiology/virology ; Extracellular Signal-Regulated MAP Kinases/immunology/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Interferon Type I/immunology/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Disease Models, Animal ; }, abstract = {Bovine viral diarrhea virus (BVDV) is prevalent worldwide and causes significant economic losses. Gut microbiota is a large microbial community and has a variety of biological functions. However, whether there is a correlation between gut microbiota and BVDV infection and what kind of relation between them have not been reported. Here, we found that gut microbiota composition changed in normal mice after infecting with BVDV, but mainly the low abundance microbe was affected. Interestingly, BVDV infection significantly reduced the diversity of gut microbiota and changed its composition in gut microbiota-dysbiosis mice. Furthermore, compared with normal mice of BVDV infection, there were more viral loads in the duodenum, jejunum, spleen, and liver of the gut microbiota-dysbiosis mice. However, feces microbiota transplantation (FMT) reversed these effects. The data above indicated that the dysbiosis of gut microbiota was a key factor in the high infection rate of BVDV. It is found that the IFN-I signal was involved by investigating the underlying mechanisms. The inhibition of the proliferation and increase in the apoptosis of peripheral blood lymphocytes (PBL) were also observed. However, FMT treatment reversed these changes by regulating PI3K/Akt, ERK, and Caspase-9/Caspase-3 pathways. Furthermore, the involvement of butyrate in the pathogenesis of BVDV was also further confirmed. Our results showed for the first time that gut microbiota acts as a key endogenous defense mechanism against BVDV infection; moreover, targeting regulation of gut microbiota structure and abundance may serve as a new strategy to prevent and control the disease.IMPORTANCEWhether the high infection rate of BVDV is related to gut microbiota has not been reported. In addition, most studies on BVDV focus on in vitro experiments, which limits the study of its prevention and control strategy and its pathogenic mechanism. In this study, we successfully confirmed the causal relationship between gut microbiota and BVDV infection as well as the potential molecular mechanism based on a mouse model of BVDV infection and a mouse model of gut microbiota dysbiosis. Meanwhile, a mouse model which is more susceptible to BVDV provided in this study lays an important foundation for further research on prevention and control strategy of BVDV and its pathogenesis. In addition, the antiviral effect of butyrate, the metabolites of butyrate-producing bacteria, has been further revealed. Overall, our findings provide a promising prevention and control strategy to treat this infectious disease which is distributed worldwide.}, }
@article {pmid38296309, year = {2024}, author = {Kragsnaes, MS and Jensen, JRB and Nilsson, AC and Malik, MI and Munk, HL and Pedersen, JK and Horn, HC and Kruhøffer, M and Kristiansen, K and Mullish, BH and Marchesi, JR and Kjeldsen, J and Röttger, R and Ellingsen, T}, title = {Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial.}, journal = {RMD open}, volume = {10}, number = {1}, pages = {}, pmid = {38296309}, issn = {2056-5933}, support = {2022-0026//Sygeforsikringen 'danmark'/ ; CL-2019-21-002//NIHR Academic Clinical Lectureship/ ; }, mesh = {Humans ; *Arthritis, Psoriatic/therapy/etiology ; Fecal Microbiota Transplantation/adverse effects ; Interleukin-6 ; Treatment Outcome ; Inflammation/etiology ; Tumor Necrosis Factor-alpha ; Antigens, Neoplasm ; Cell Adhesion Molecules ; }, abstract = {OBJECTIVES: The gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on 92 inflammation-associated plasma proteins.<br><br>METHODS: This study relates to the FLORA trial cohort, where 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate treatment, were included in a 26-week, double-blind, randomised, sham-controlled trial. Participants were allocated to receive either one gastroscopic-guided healthy donor FMT (n=15) or sham (n=16). Patient plasma samples were collected at baseline, week 4, 12 and 26 while samples from 31 age-matched and sex-matched healthy controls (HC) were collected at baseline. Samples were analysed using proximity extension assay technology (Olink Target-96 Inflammation panel).<br><br>RESULTS: Levels of 26 proteins differed significantly between PsA and HC pre-FMT (adjusted p<0.05), of which 10 proteins were elevated in PsA: IL-6, CCL20, CCL19, CDCP1, FGF-21, HGF, interferon-&#x3b3; (IFN-&#x3b3;), IL-18R1, monocyte chemotactic protein 3, and IL-2. In the FMT group, levels of 12 proteins changed significantly across all timepoints (tumour necrosis factor (TNF), CDCP1, IFN-&#x3b3;, TWEAK, signalling lymphocytic activation molecule (SLAMF1), CD8A, CD5, Flt3L, CCL25, FGF-23, CD6, caspase-8). Significant differences in protein levels between FMT and sham-treated patients were observed for TNF (p=0.002), IFN-&#x3b3; (p=0.011), stem cell factor (p=0.024), matrix metalloproteinase-1 (p=0.038), and SLAMF1 (p=0.042). FMT had the largest positive effect on IFN-&#x3b3;, Axin-1 and CCL25 and the largest negative effect on CCL19 and IL-6.<br><br>CONCLUSIONS: Patients with active PsA have a distinct immunological plasma protein signature compared with HC pre-FMT. FMT affects several of these disease markers, including sustained elevation of IFN-&#x3b3;.<br><br>TRIAL REGISTRATION NUMBER: NCT03058900.}, }
@article {pmid38296308, year = {2024}, author = {Gilbert, BTP and Tadeo, RYT and Lamacchia, C and Studer, O and Courvoisier, D and Raes, J and Finckh, A}, title = {Gut microbiome and intestinal inflammation in preclinical stages of rheumatoid arthritis.}, journal = {RMD open}, volume = {10}, number = {1}, pages = {}, pmid = {38296308}, issn = {2056-5933}, mesh = {Humans ; Autoantibodies ; *Gastrointestinal Microbiome ; *Arthritis, Rheumatoid ; Inflammation ; Leukocyte L1 Antigen Complex ; }, abstract = {BACKGROUND: Faecal Prevotellaceae, and other microbes, have been associated with rheumatoid arthritis (RA) and preclinical RA. We have performed a quantitative microbiome profiling study in preclinical stages of RA.<br><br>METHODS: First-degree relatives of patients with RA (RA-FDRs) from the SCREEN-RA cohort were categorised into four groups: controls, healthy asymptomatic RA-FDRs; high genetic risk, asymptomatic RA-FDRs with two copies of the shared epitope; autoimmunity, asymptomatic RA-FDRs with RA-associated autoimmunity; and symptomatic, clinically suspect arthralgias or untreated new-onset RA.Faecal samples were collected and frozen. 16S sequencing was performed, processed with DADA2 pipeline and Silva database. Cell counts (cytometry) and faecal calprotectin (enzyme-linked immunosorbent assay, ELISA) were also obtained. Microbial community analyses were conducted using non-parametric tests, such as permutational multivariate analysis of variance (PERMANOVA), Wilcoxon and Kruskal-Wallis, or Aldex2.<br><br>RESULTS: A total of 371 individuals were included and categorised according to their preclinical stage of the disease. Groups had similar age, gender and body mass index. We found no significant differences in the quantitative microbiome profiles by preclinical stages (PERMANOVA, R2=0.00798, p=0.56) and, in particular, no group differences in Prevotellaceae abundance. Results were similar when using relative microbiome profiling data (PERMANOVA, R2=0.0073, p=0.83) or Aldex2 on 16S sequence counts. Regarding faecal calprotectin, we found no differences between groups (p=0.3).<br><br>CONCLUSIONS: We could not identify microbiome profiles associated with preclinical stages of RA. Only in a subgroup of individuals with the most pronounced phenotypes did we modestly retrieve the previously reported associations.}, }
@article {pmid38296019, year = {2024}, author = {Wei, J and Wang, G and Lai, M and Zhang, Y and Li, F and Wang, Y and Tan, Y}, title = {Faecal Microbiota Transplantation Alleviates Ferroptosis after Ischaemic Stroke.}, journal = {Neuroscience}, volume = {541}, number = {}, pages = {91-100}, doi = {10.1016/j.neuroscience.2024.01.021}, pmid = {38296019}, issn = {1873-7544}, mesh = {Male ; Animals ; Rats ; Rats, Sprague-Dawley ; *Stroke/therapy ; Fecal Microbiota Transplantation ; *Brain Ischemia/therapy ; *Ferroptosis ; *Ischemic Stroke/therapy ; Chlorides ; Glutathione ; Iron ; }, abstract = {Ischaemic stroke can induce changes in the abundance of gut microbiota constituents, and the outcome of stroke may also be influenced by the gut microbiota. This study aimed to determine whether gut microbiota transplantation could rescue changes in the gut microbiota and reduce ferroptosis after stroke in rats. Male Sprague-Dawley rats (6 weeks of age) were subjected to ischaemic stroke by middle cerebral artery occlusion (MCAO). Fecal samples were collected for 16S ribosomal RNA (rRNA) sequencing to analyze the effects of FMT on the gut microbiota. Neurological deficits were evaluated using the Longa score. triphenyl tetrazolium chloride (TTC) staining was performed in the brain, and kits were used to measure malondialdehyde (MDA), iron, and glutathione (GSH) levels in the ipsilateral brain of rats. Western blotting was used to detect the protein expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and the transferrin receptor 2 (TFR2) in the ipsilateral brain of rats. Stroke induced significant changes in the gut microbiota, and FMT ameliorated these changes. TTC staining results showed that FMT reduced cerebral infarct volume. In addition, FMT diminished MDA and iron levels and elevated GSH levels in the ipsilateral brain. Western blot analysis showed that FMT increased GPX4 and SLC7A11 protein expression and decreased TFR2 protein expression in the ipsilateral brain after stroke. FMT can reverse gut microbiota dysbiosis, reduce cerebellar infarct volume, and decrease ferroptosis after stroke.}, }
@article {pmid38294580, year = {2024}, author = {Dong, L and Tang, Y and Wen, S and He, Y and Li, F and Deng, Y and Tao, Z}, title = {Fecal Microbiota Transplantation Alleviates Allergic Rhinitis via CD4[+] T Cell Modulation Through Gut Microbiota Restoration.}, journal = {Inflammation}, volume = {47}, number = {4}, pages = {1278-1297}, pmid = {38294580}, issn = {1573-2576}, support = {81970860//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; *Rhinitis, Allergic/therapy/immunology/microbiology ; Mice ; *CD4-Positive T-Lymphocytes/immunology/metabolism ; Cytokines/metabolism ; Nasal Mucosa/immunology/microbiology/metabolism ; Ovalbumin/immunology ; Signal Transduction ; Mice, Inbred BALB C ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {Allergic rhinitis (AR) is an allergic condition of the upper respiratory tract with a complex pathogenesis, including epithelial barrier disruption, immune regulation, and gut microbiota, which is not yet fully understood. Gut microbiota is closely linked to allergic diseases, including AR. Fecal microbiota transplantation (FMT) has recently been recognized as a potentially effective therapy for allergic diseases. However, the efficacy and mechanism of action of FMT in AR remain unknown. Herein, we aimed to observe the implications of gut microbiota on epithelial barrier function and T cell homeostasis, as well as the effect of FMT in AR, using the ovalbumin (OVA)-induced AR mice. The intestinal microbiota of recipient mice was cleared using an antibiotic cocktail; thereafter, FMT was performed. Subsequently, the nasal symptom scores and histopathological features of colon and nasal mucosa tissues of mice were monitored, and serum OVA-sIgE and cytokines of IL-4, IFNγ, IL-17A, and IL-10 cytokine concentrations were examined. Thereafter, tight junction protein and CD4[+] T cell-related transcription factor and cytokine expressions were observed in the colon and nasal mucosa, and changes in the expression of PI3K/AKT/mTOR and NFκB signaling pathway were detected by WB assay in each group. Fecal DNA was extracted from the four mice groups for high-throughput 16S rRNA sequencing. FMT ameliorated nasal symptoms and reduced nasal mucosal inflammation in AR mice. Moreover, according to 16S rRNA sequencing, FMT restored the disordered gut microbiota in AR mice. Following FMT, ZO-1 and claudin-1 and Th1/Th2/Th17-related transcription factor and cytokine expressions were upregulated, whereas Treg cell-related Foxp3 and IL-10 expressions were downregulated. Mechanistic studies have revealed that FMT also inhibited PI3K/AKT/mTOR and NF-κB pathway protein phosphorylation in AR mouse tissues. FMT alleviates allergic inflammation in AR by repairing the epithelial barrier and modulating CD4[+] T cell balance and exerts anti-inflammatory effects through the PI3K/AKT/mTOR and NF-κB signaling pathways. Moreover, gut microbiota disorders are involved in AR pathogenesis. Disturbed gut microbiota causes an altered immune-inflammatory state in mice and increases susceptibility to AR. This study suggested the regulatory role of the gut-nose axis in the pathogenesis of AR is an emerging field, which provides novel directions and ideas for the treatment of AR.}, }
@article {pmid38293097, year = {2024}, author = {Ma, L and Ge, Y and Brown, J and Choi, SC and Elshikha, A and Kanda, N and Terrell, M and Six, N and Garcia, A and Mohamadzadeh, M and Silverman, G and Morel, L}, title = {Dietary tryptophan and genetic susceptibility expand gut microbiota that promote systemic autoimmune activation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38293097}, issn = {2692-8205}, support = {P30 CA054174/CA/NCI NIH HHS/United States ; R01 AI143313/AI/NIAID NIH HHS/United States ; S10 OD030432/OD/NIH HHS/United States ; }, abstract = {Tryptophan modulates disease activity and the composition of microbiota in the B6.Sle1.Sle2.Sle3 (TC) mouse model of lupus. To directly test the effect of tryptophan on the gut microbiome, we transplanted fecal samples from TC and B6 control mice into germ-free or antibiotic-treated non-autoimmune B6 mice that were fed with a high or low tryptophan diet. The recipient mice with TC microbiota and high tryptophan diet had higher levels of immune activation, autoantibody production and intestinal inflammation. A bloom of Ruminococcus gnavus (Rg), a bacterium associated with disease flares in lupus patients, only emerged in the recipients of TC microbiota fed with high tryptophan. Rg depletion in TC mice decreased autoantibody production and increased the frequency of regulatory T cells. Conversely, TC mice colonized with Rg showed higher autoimmune activation. Overall, these results suggest that the interplay of genetic and tryptophan can influence the pathogenesis of lupus through the gut microbiota.}, }
@article {pmid38292634, year = {2024}, author = {Xu, TC and Liu, Y and Yu, Z and Xu, B}, title = {Gut-targeted therapies for type 2 diabetes mellitus: A review.}, journal = {World journal of clinical cases}, volume = {12}, number = {1}, pages = {1-8}, pmid = {38292634}, issn = {2307-8960}, abstract = {Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance. The global prevalence of T2DM has reached epidemic proportions, affecting approximately 463 million adults worldwide in 2019. Current treatments for T2DM include lifestyle modifications, oral antidiabetic agents, and insulin therapy. However, these therapies may carry side effects and fail to achieve optimal glycemic control in some patients. Therefore, there is a growing interest in the role of gut microbiota and more gut-targeted therapies in the management of T2DM. The gut microbiota, which refers to the community of microorganisms that inhabit the human gut, has been shown to play a crucial role in the regulation of glucose metabolism and insulin sensitivity. Alterations in gut microbiota composition and diversity have been observed in T2DM patients, with a reduction in beneficial bacteria and an increase in pathogenic bacteria. This dysbiosis may contribute to the pathogenesis of the disease by promoting inflammation and impairing gut barrier function. Several gut-targeted therapies have been developed to modulate the gut microbiota and improve glycemic control in T2DM. One potential approach is the use of probiotics, which are live microorganisms that confer health benefits to the host when administered in adequate amounts. Several randomized controlled trials have demonstrated that certain probiotics, such as Lactobacillus and Bifidobacterium species, can improve glycemic control and insulin sensitivity in T2DM patients. Mechanisms may include the production of short-chain fatty acids, the improvement of gut barrier function, and the reduction of inflammation. Another gut-targeted therapy is fecal microbiota transplantation (FMT), which involves the transfer of fecal material from a healthy donor to a recipient. FMT has been used successfully in the treatment of Clostridioides difficile infection and is now being investigated as a potential therapy for T2DM. A recent randomized controlled trial showed that FMT from lean donors improved glucose metabolism and insulin sensitivity in T2DM patients with obesity. However, FMT carries potential risks, including transmission of infectious agents and alterations in the recipient's gut microbiota that may be undesirable. In addition to probiotics and FMT, other gut-targeted therapies are being investigated for the management of T2DM, such as prebiotics, synbiotics, and postbiotics. Prebiotics are dietary fibers that promote the growth of beneficial gut bacteria, while synbiotics combine probiotics and prebiotics. Postbiotics refer to the metabolic products of probiotics that may have beneficial effects on the host. The NIH SPARC program, or the Stimulating Peripheral Activity to Relieve Conditions, is a research initiative aimed at developing new therapies for a variety of health conditions, including T2DM. The SPARC program focuses on using electrical stimulation to activate peripheral nerves and organs, in order to regulate glucose levels in the body. The goal of this approach is to develop targeted, non-invasive therapies that can help patients better manage their diabetes. One promising area of research within the SPARC program is the use of electrical stimulation to activate the vagus nerve, which plays an important role in regulating glucose metabolism. Studies have shown that vagus nerve stimulation can improve insulin sensitivity and lower blood glucose levels in patients with T2DM. Gut-targeted therapies, such as probiotics and FMT, have shown potential for improving glycemic control and insulin sensitivity in T2DM patients. However, further research is needed to determine the optimal dose, duration, and safety of these therapies.}, }
@article {pmid38292322, year = {2024}, author = {Huang, T and Lv, Y and Wang, W and Chen, Y and Fan, L and Teng, Z and Zhou, X and Shen, H and Fu, G}, title = {Case Report: Fecal Microbiota Transplantation for the Treatment of Generalized Eczema Occurring After COVID-19 Vaccination.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {17}, number = {}, pages = {229-235}, pmid = {38292322}, issn = {1178-7015}, abstract = {Adverse skin reactions caused by the COVID-19 vaccine have attracted considerable attention. As we all know, the development mechanism of some skin diseases is related to the gut and skin microbiome. A 78-year-old male patient who received the COVID-19 vaccine developed generalized eczema with multiple dense black patches over the body, a widespread rash, erosion, and scabs on his limbs, as well as facial edema. The patient experienced recurrent flare-ups after conventional treatment, but then recovered well without recurrence after undergoing three fecal microbial transplantation (FMT) treatments. This rare case is reported for the first time in this study. This report demonstrates the possible potential of FMT in targeting refractory skin diseases, such as eczema, as well as diseases associated with gut microbiota disturbance after vaccination.}, }
@article {pmid38288791, year = {2024}, author = {Bahmani, M and Mehrtabar, S and Jafarizadeh, A and Zoghi, S and Heravi, FS and Abbasi, A and Sanaie, S and Rahnemayan, S and Leylabadlo, HE}, title = {The Gut Microbiota and Major Depressive Disorder: Current Understanding and Novel Therapeutic Strategies.}, journal = {Current pharmaceutical biotechnology}, volume = {25}, number = {16}, pages = {2089-2107}, pmid = {38288791}, issn = {1873-4316}, support = {Grant number: 71737//Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Depressive Disorder, Major/microbiology/therapy ; *Probiotics/therapeutic use ; *Prebiotics/administration &amp; dosage ; *Fecal Microbiota Transplantation ; Animals ; Synbiotics/administration &amp; dosage ; }, abstract = {Major depressive disorder (MDD) is a common neuropsychiatric challenge that primarily targets young females. MDD as a global disorder has a multifactorial etiology related to the environment and genetic background. A balanced gut microbiota is one of the most important environmental factors involved in human physiological health. The interaction of gut microbiota components and metabolic products with the hypothalamic-pituitary-adrenal system and immune mediators can reverse depression phenotypes in vulnerable individuals. Therefore, abnormalities in the quantitative and qualitative structure of the gut microbiota may lead to the progression of MDD. In this review, we have presented an overview of the bidirectional relationship between gut microbiota and MDD, and the effect of pre-treatments and microbiomebased approaches, such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and a new generation of microbial alternatives, on the improvement of unstable clinical conditions caused by MDD.}, }
@article {pmid38287975, year = {2023}, author = {Wetzel, S and Müller, A and Kohnert, E and Mehrbarzin, N and Huber, R and Häcker, G and Kreutz, C and Lederer, AK and Badr, MT}, title = {Longitudinal dynamics of gut bacteriome and mycobiome interactions pre- and post-visceral surgery in Crohn's disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1275405}, pmid = {38287975}, issn = {2235-2988}, mesh = {Humans ; *Mycobiome ; *Crohn Disease/surgery ; RNA, Ribosomal, 16S/genetics ; Prospective Studies ; Bacteria/genetics ; *Digestive System Surgical Procedures ; Fungi/genetics ; }, abstract = {INTRODUCTION: Alterations of the gut microbiome are involved in the pathogenesis of Crohn's disease (CD). The role of fungi in this context is unclear. This study aimed to determine postoperative changes in the bacterial and fungal gut communities of CD patients undergoing intestinal resection, and to evaluate interactions between the bacteriome and mycobiome and their impact on the patients' outcome.<br><br>METHODS: We report a subgroup analysis of a prospective cohort study, focusing on 10 CD patients whose fecal samples were collected for bacterial 16S rRNA and fungal ITS2 genes next-generation sequencing the day before surgery and on the 5th or 6th postoperative day.<br><br>RESULTS: No significant differences in bacterial and fungal diversity were observed between preoperative and postoperative stool samples. By in-depth analysis, significant postoperative abundance changes of bacteria and fungi and 17 interkingdom correlations were detected. Network analysis identified 13 microbial clusters in the perioperative gut communities, revealing symbiotic and competitive interactions. Relevant factors were gender, age, BMI, lifestyle habits (smoking, alcohol consumption) and surgical technique. Postoperative abundance changes and identified clusters were associated with clinical outcomes (length of hospital stay, complications) and levels of inflammatory markers.<br><br>CONCLUSIONS: Our findings highlight the importance of dissecting the interactions of gut bacterial and fungal communities in CD patients and their potential influence on postoperative and disease outcomes.}, }
@article {pmid38287961, year = {2023}, author = {Li, H and Lv, N and Li, D and Qian, Y and Si, X and Hua, Y and Wang, Y and Han, X and Xu, T}, title = {Tongbian decoction restores intestinal microbiota and activates 5-hydroxytryptamine signaling: implication in slow transit constipation.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1296163}, pmid = {38287961}, issn = {1664-302X}, abstract = {INTRODUCTION: Slow transit constipation (STC) is a type of functional constipation. The detailed mechanism of STC, for which there is currently no effective treatment, is unknown as of yet. Tongbian decoction (TBD), a traditional Chinese medicinal formula, is commonly used to treat STC in clinical settings. However, the potential impact of TBD on the management of STC via modulation of the gut microbiota remains unclear.<br><br>METHODS: Pseudo-germ-free rats were constructed after 6&#x2009;days of treatment with bacitracin, neomycin, and streptomycin (abbreviated as ABX forthwith). Based on the successful construction of pseudo-germ-free rats, the STC model (ABX&#x2009;+&#x2009;STC) was induced using loperamide hydrochloride. After successful modeling, based on the different sources of donor rat microbiota, the ABX&#x2009;+&#x2009;STC rats were randomly divided into three groups: Control &#x2192; ABX&#x2009;+&#x2009;STC, STC&#x2009;&#x2192;&#x2009;ABX&#x2009;+&#x2009;STC, and STC&#x2009;+&#x2009;TBD&#x2009;&#x2192;&#x2009;ABX&#x2009;+&#x2009;STC for fecal microbiota transplant (FMT). Body weight, fecal water content, and charcoal power propelling rate of the rats were recorded. Intestinal microbiota was detected by 16S rRNA sequencing, and the 5-hydroxytryptamine (5-HT) signaling pathway was examined by western blots, immunofluorescence, and immunohistochemical analysis.<br><br>RESULTS: After treatment with fecal bacterial solutions derived from rats treated with Tongbian decoction (TBD), there was an increase in body weight, fecal water content, and the rate of charcoal propulsion in the rats. Additionally, activation of the 5-hydroxytryptamine (5-HT) signaling pathway was observed. The 16S rRNA sequencing results showed that the fecal bacterial solution from TBD-treated rats affected the intestinal microbiota of STC rats by increasing the proliferation of beneficial bacteria and suppressing the expansion of harmful bacteria.<br><br>CONCLUSION: Our study showed that TBD alleviated constipation in STC rats by modulating the structure of the intestinal microbiota.}, }
@article {pmid38283489, year = {2023}, author = {Sinnathamby, ES and Mason, JW and Flanagan, CJ and Pearl, NZ and Burroughs, CR and De Witt, AJ and Wenger, DM and Klapper, VG and Ahmadzadeh, S and Varrassi, G and Shekoohi, S and Kaye, AD}, title = {Clostridioides difficile Infection: A Clinical Review of Pathogenesis, Clinical Considerations, and Treatment Strategies.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e51167}, pmid = {38283489}, issn = {2168-8184}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is a common nosocomial infection. Risk factors for developing CDI include prior hospitalization, being older than 65 years old, antibiotic use, and chronic disease. It is linked with diarrhea and colitis and can vary in severity. It is a major cause of increased morbidity and mortality among hospitalized patients. However, community-acquired CDI is also increasing. Proper diagnosis and determination of severity are crucial for the treatment of CDI. Depending on how severe the CDI is, the patient may endorse different symptoms and physical exam findings. The severity of CDI will determine how aggressively it is treated. Management and treatment: Laboratory studies can be helpful in the diagnosis of CDI. In this regard, common labs include complete blood count, stool assays, and, in certain cases, radiography and endoscopy. Mild-to-moderate colitis is treated with antibiotics, but severe colitis requires a different approach, which may include surgery. Several alternative therapies for CDI exist and have shown promising results. This review will touch upon these therapies, which include fecal transplants, intravenous immunoglobulin, and the use of cholestyramine and tigecycline.<br><br>CONCLUSION: Prevention of CDI can be achieved by proper hygiene, vaccinations, and detecting the infection early. Proper hygiene is indeed noted to be one of the best ways to prevent CDI in the hospital setting. Overprescribing antibiotics is also another huge reason why CDI occurs. Proper prescription of antibiotics can also help reduce the chances of acquiring CDI.}, }
@article {pmid38281930, year = {2024}, author = {Sabbaghian, M and Gheitasi, H and Shekarchi, AA and Tavakoli, A and Poortahmasebi, V}, title = {The mysterious anelloviruses: investigating its role in human diseases.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {40}, pmid = {38281930}, issn = {1471-2180}, mesh = {Humans ; *Anelloviridae/genetics ; *DNA Virus Infections/epidemiology ; *Torque teno virus/genetics ; *Body Fluids ; Liver ; DNA, Viral ; }, abstract = {Anelloviruses (AVs) that infect the human population are members of the Anelloviridae family. They are widely distributed in human populations worldwide. Torque teno virus (TTV) was the first virus of this family to be identified and is estimated to be found in the serum of 80-90% of the human population. Sometime after the identification of TTV, Torque teno mini virus (TTMV) and Torque teno midi virus (TTMDV) were also identified and classified in this family. Since identifying these viruses, have been detected in various types of biological fluids of the human body, including blood and urine, as well as vital organs such as the liver and kidney. They can be transmitted from person to person through blood transfusions, fecal-oral contact, and possibly sexual intercourse. Recent studies on these newly introduced viruses show that although they are not directly related to human disease, they may be indirectly involved in initiating or exacerbating some human population-related diseases and viral infections. Among these diseases, we can mention various types of cancers, immune system diseases, viral infections, hepatitis, and AIDS. Also, they likely use the microRNAs (miRNAs) they encode to fulfill this cooperative role. Also, in recent years, the role of proliferation and their viral load, especially TTV, has been highlighted to indicate the immune system status of immunocompromised people or people who undergo organ transplants. Here, we review the possible role of these viruses in diseases that target humans and highlight them as important viruses that require further study. This review can provide new insights to researchers.}, }
@article {pmid38281337, year = {2024}, author = {Ren, P and Yue, H and Tang, Q and Wang, Y and Xue, C}, title = {Astaxanthin exerts an adjunctive anti-cancer effect through the modulation of gut microbiota and mucosal immunity.}, journal = {International immunopharmacology}, volume = {128}, number = {}, pages = {111553}, doi = {10.1016/j.intimp.2024.111553}, pmid = {38281337}, issn = {1878-1705}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Immunity, Mucosal ; Intestines/pathology ; Intestinal Mucosa ; Xanthophylls ; }, abstract = {This study aimed to investigate the function of gut microbiota in astaxanthin's adjuvant anticancer effects. Our prior research demonstrated that astaxanthin enhanced the antitumor effects of sorafenib by enhancing the body's antitumor immune response; astaxanthin also regulated the intestinal flora composition of tumor-bearing mice. However, it is presently unknown whether this beneficial effect is dependent on the gut microbiota. We first used broad-spectrum antibiotics to eradicate gut microbiota of tumor-bearing mice, followed by the transplantation of fecal microbiota. The results of this study indicate that the beneficial effects of astaxanthin when combined with molecular targeting are dependent on the presence of intestinal microbiota. Astaxanthin facilitates the infiltration of CD8+ T lymphocytes into the tumor microenvironment and increases Granzyme B production by modulating the intestinal flora. Therefore, it strengthens the body's anti-tumor immune response and synergistically boosts the therapeutic efficacy of drugs. Astaxanthin stimulates the production of cuprocytes and mucus in the intestines by promoting the proliferation of Akkermansia. In addition, astaxanthin enhances the intestinal mucosal immunological function. Our research supports the unique ability of astaxanthin to sustain intestinal flora homeostasis and its function as a dietary immune booster for individuals with tumors.}, }
@article {pmid38280701, year = {2024}, author = {Liu, M and Ma, J and Xu, J and Huangfu, W and Zhang, Y and Ali, Q and Liu, B and Li, D and Cui, Y and Wang, Z and Sun, H and Zhu, X and Ma, S and Shi, Y}, title = {Fecal microbiota transplantation alleviates intestinal inflammatory diarrhea caused by oxidative stress and pyroptosis via reducing gut microbiota-derived lipopolysaccharides.}, journal = {International journal of biological macromolecules}, volume = {261}, number = {Pt 1}, pages = {129696}, doi = {10.1016/j.ijbiomac.2024.129696}, pmid = {38280701}, issn = {1879-0003}, mesh = {Infant ; Humans ; Animals ; Swine ; *Fecal Microbiota Transplantation/adverse effects/methods ; Lipopolysaccharides ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; Pyroptosis ; Diarrhea/microbiology ; Oxidative Stress ; }, abstract = {Infancy is a critical period in the maturation of the gut microbiota and a phase of susceptibility to gut microbiota dysbiosis. Early disturbances in the gut microbiota can have long-lasting effects on host physiology, including intestinal injury and diarrhea. Fecal microbiota transplantation (FMT) can remodel gut microbiota and may be an effective way to treat infant diarrhea. However, limited research has been conducted on the mechanisms of infant diarrhea and the regulation of gut microbiota balance through FMT, primarily due to ethical challenges in testing on human infants. Our study demonstrated that elevated Lipopolysaccharides (LPS) levels in piglets with diarrhea were associated with colon microbiota dysbiosis induced by early weaning. Additionally, LPS upregulated NLRP3 levels by activating TLR4 and inducing ROS production, resulting in pyroptosis, disruption of the intestinal barrier, bacterial translocation, and subsequent inflammation, ultimately leading to diarrhea in piglets. Through microbiota regulation, FMT modulated β-PBD-2 secretion in the colon by increasing butyric acid levels. This modulation alleviated gut microbiota dysbiosis, reduced LPS levels, attenuated oxidative stress and pyroptosis, inhibited the inflammatory response, maintained the integrity of the intestinal barrier, and ultimately reduced diarrhea in piglets caused by colitis. These findings present a novel perspective on the pathogenesis, pathophysiology, prevention, and treatment of diarrhea diseases, underscoring the significance of the interaction between FMT and the gut microbiota as a critical strategy for treating diarrhea and intestinal diseases in infants and farm animals.}, }
@article {pmid38280329, year = {2024}, author = {Hu, L and Feng, X and Lan, Y and Zhang, J and Nie, P and Xu, H}, title = {Co-exposure with cadmium elevates the toxicity of microplastics: Trojan horse effect from the perspective of intestinal barrier.}, journal = {Journal of hazardous materials}, volume = {466}, number = {}, pages = {133587}, doi = {10.1016/j.jhazmat.2024.133587}, pmid = {38280329}, issn = {1873-3336}, mesh = {Animals ; Mice ; *Cadmium/toxicity ; Microplastics/toxicity ; Plastics/toxicity ; *Metals, Heavy/toxicity ; Oxidative Stress ; Polystyrenes/pharmacology ; }, abstract = {Microplastics (MPs) have been shown to adsorb heavy metals and serve as vehicles for their environmental transport. To date, insufficient studies have focused on enterohepatic injury in mice co-exposed to both MPs and cadmium (Cd). Here, we report that Cd adsorption increased the surface roughness and decreased the monodispersity of PS-MPs. Furthermore, exposure to both PS-MPs and Cd resulted in a more severe toxic effect compared to single exposure, with decreased body weight gain, shortened colon length, and increased colonic and hepatic inflammatory response observed. This can be attributed to an elevated accumulation of Cd resulting from increased gut permeability, coupled with the superimposed effects of oxidative stress. In addition, using 16 S sequencing and fecal microbiota transplantation, it was demonstrated that gut microbiota dysbiosis plays an essential role in the synergistic toxicity induced by PS-MPs and Cd in mice. This study showed that combined exposure to MPs and Cd induced more severe intestinal and liver damage in mice compared to individual exposure, and provided a new perspective for a more systematic risk assessment process related to MPs exposure.}, }
@article {pmid38276546, year = {2024}, author = {Czarnik, W and Fularski, P and Gajewska, A and Jakubowska, P and Uszok, Z and Młynarska, E and Rysz, J and Franczyk, B}, title = {The Role of Intestinal Microbiota and Diet as Modulating Factors in the Course of Alzheimer's and Parkinson's Diseases.}, journal = {Nutrients}, volume = {16}, number = {2}, pages = {}, pmid = {38276546}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Parkinson Disease/therapy ; *Alzheimer Disease ; Diet ; *Microbiota ; Dysbiosis ; Brain ; }, abstract = {Many researchers propose manipulating microbiota to prevent and treat related diseases. The brain-gut axis is an object that remains the target of modern research, and it is not without reason that many researchers enrich it with microbiota and diet in its name. Numerous connections and mutual correlations have become the basis for seeking answers to many questions related to pathology as well as human physiology. Disorders of this homeostasis as well as dysbiosis itself accompany neurodegenerative diseases such as Alzheimer's and Parkinson's. Heavily dependent on external factors, modulation of the gut microbiome represents an opportunity to advance the treatment of neurodegenerative diseases. Probiotic interventions, synbiotic interventions, or fecal transplantation can undoubtedly support the biotherapeutic process. A special role is played by diet, which provides metabolites that directly affect the body and the microbiota. A holistic view of the human organism is therefore essential.}, }
@article {pmid38276309, year = {2024}, author = {Gurung, B and Stricklin, M and Wang, S}, title = {Gut Microbiota-Gut Metabolites and Clostridioides difficile Infection: Approaching Sustainable Solutions for Therapy.}, journal = {Metabolites}, volume = {14}, number = {1}, pages = {}, pmid = {38276309}, issn = {2218-1989}, support = {19168-20-4250002//Start-up funding and RSAC (Research and Scholarly Awards Committee) pilot grant support from Ohio University Heritage College of Osteopathic Medicine/ ; }, abstract = {Clostridioides difficile (C. difficile) infection (CDI) is the most common hospital-acquired infection. With the combination of a high rate of antibiotic resistance and recurrence, it has proven to be a debilitating public health threat. Current treatments for CDI include antibiotics and fecal microbiota transplantation, which contribute to recurrent CDIs and potential risks. Therefore, there is an ongoing need to develop new preventative treatment strategies for CDI. Notably, gut microbiota dysbiosis is the primary risk factor for CDI and provides a promising target for developing novel CDI therapy approaches. Along with gut microbiota dysbiosis, a reduction in important gut metabolites like secondary bile acids and short-chain fatty acids (SCFAs) were also seen in patients suffering from CDI. In this review study, we investigated the roles and mechanisms of gut microbiota and gut microbiota-derived gut metabolites, especially secondary bile acids and SCFAs in CDI pathogenesis. Moreover, specific signatures of gut microbiota and gut metabolites, as well as different factors that can modulate the gut microbiota, were also discussed, indicating that gut microbiota modulators like probiotics and prebiotics can be a potential therapeutic strategy for CDI as they can help restore gut microbiota and produce gut metabolites necessary for a healthy gut. The understanding of the associations between gut microbiota-gut metabolites and CDI will allow for developing precise and sustainable approaches, distinct from antibiotics and fecal transplant, for mitigating CDI and other gut microbiota dysbiosis-related diseases.}, }
@article {pmid38276223, year = {2023}, author = {Suswał, K and Tomaszewski, M and Romaniuk, A and Świechowska-Starek, P and Zygmunt, W and Styczeń, A and Romaniuk-Suswał, M}, title = {Gut-Lung Axis in Focus: Deciphering the Impact of Gut Microbiota on Pulmonary Arterial Hypertension.}, journal = {Journal of personalized medicine}, volume = {14}, number = {1}, pages = {}, pmid = {38276223}, issn = {2075-4426}, support = {DS 640//Polish Society of Cardiology/ ; }, abstract = {Recent advancements in the understanding of pulmonary arterial hypertension (PAH) have highlighted the significant role of the gut microbiota (GM) in its pathogenesis. This comprehensive review delves into the intricate relationship between the GM and PAH, emphasizing the influence of gut microbial composition and the critical metabolites produced. We particularly focus on the dynamic interaction between the gut and lung, examining how microbial dysbiosis contributes to PAH development through inflammation, altered immune responses, and changes in the gut-lung axis. Noteworthy findings include variations in the ratios of key bacterial groups such as Firmicutes and Bacteroidetes in PAH and the pivotal roles of metabolites like trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and serotonin in the disease's progression. Additionally, the review elucidates potential diagnostic biomarkers and novel therapeutic approaches, including the use of probiotics and fecal microbiota transplantation, which leverage the gut microbiota for managing PAH. This review encapsulates the current state of research in this field, offering insights into the potential of gut microbiota modulation as a promising strategy in PAH diagnosing and treatment.}, }
@article {pmid38275924, year = {2024}, author = {Rojas, CA and Entrolezo, Z and Jarett, JK and Jospin, G and Martin, A and Ganz, HH}, title = {Microbiome Responses to Oral Fecal Microbiota Transplantation in a Cohort of Domestic Dogs.}, journal = {Veterinary sciences}, volume = {11}, number = {1}, pages = {}, pmid = {38275924}, issn = {2306-7381}, abstract = {Fecal microbiota transplants (FMTs) have been successful at treating digestive and skin conditions in dogs. The degree to which the microbiome is impacted by FMT in a cohort of dogs has not been thoroughly investigated. Using 16S rRNA gene sequencing, we document the changes in the microbiome of fifty-four dogs that took capsules of lyophilized fecal material for their chronic diarrhea, vomiting, or constipation. We found that the relative abundances of five bacterial genera (Butyricicoccus, Faecalibacterium, Fusobacterium, Megamonas, and Sutterella) were higher after FMT than before FMT. Fecal microbiome alpha- and beta-diversity were correlated with kibble and raw food consumption, and prior antibiotic use. On average, 18% of the stool donor's bacterial amplicon sequence variants (ASVs) engrafted in the FMT recipient, with certain bacterial taxa like Bacteroides spp., Fusobacterium spp., and Lachnoclostridium spp. engrafting more frequently than others. Lastly, analyses indicated that the degree of overlap between the donor bacteria and the community of microbes already established in the FMT recipient likely impacts engraftment. Collectively, our work provides further insight into the microbiome and engraftment dynamics of dogs before and after taking oral FMTs.}, }
@article {pmid38274729, year = {2023}, author = {Wang, L and Xu, A and Wang, J and Fan, G and Liu, R and Wei, L and Pei, M}, title = {The effect and mechanism of Fushen Granule on gut microbiome in the prevention and treatment of chronic renal failure.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1334213}, pmid = {38274729}, issn = {2235-2988}, mesh = {Humans ; Rats ; Animals ; *Gastrointestinal Microbiome ; Creatinine/therapeutic use ; *Kidney Failure, Chronic/drug therapy/metabolism ; Lactobacillus ; Lactates/therapeutic use ; Endotoxins ; }, abstract = {BACKGROUND: Fushen Granule is an improved granule based on the classic formula Fushen Formula, which is used for the treatment of peritoneal dialysis-related intestinal dysfunction in patients with end-stage renal disease. However, the effect and mechanism of this granule on the prevention and treatment of chronic renal failure have not been fully elucidated.<br><br>METHODS: A 5/6 nephrectomy model of CRF was induced and Fushen Granule was administered at low and high doses to observe its effects on renal function, D-lactate, serum endotoxin, and intestinal-derived metabolic toxins. The 16SrRNA sequencing method was used to analyze the abundance and structure of the intestinal flora of CRF rats. A FMT assay was also used to evaluate the effects of transplantation of Fushen Granule fecal bacteria on renal-related functional parameters and metabolic toxins in CRF rats.<br><br>RESULTS: Gavage administration of Fushen Granule at low and high doses down-regulated creatinine, urea nitrogen, 24-h urine microalbumin, D-lactate, endotoxin, and the intestinal-derived toxins indophenol sulphateand p-cresol sulphate in CRF rats. Compared with the sham-operated group in the same period, CRF rats had a decreased abundance of the firmicutes phylum and an increased abundance of the bacteroidetes phylum at the phylum level, and a decreasing trend of the lactobacillus genus at the genus level. Fushen Granule intervention increased the abundance of the firmicutes phylum, decreased the abundance of the bacteroidetes phylum, and increased the abundance of the lactobacillus genus. The transplantation of Fushen Granule fecal bacteria significantly reduced creatinine(Cr), blood urea nitrogen(Bun), uric acid(UA), 24-h urinary microalbumin, D-lactate, serum endotoxin, and enterogenic metabolic toxins in CRF rats. Compared with the sham-operated group, the transplantation of Fushen Granule fecal bacteria modulated the Firmicutes and Bacteroidetes phyla and the Lactobacillus genus.<br><br>CONCLUSION: Fushen Granule improved renal function and intestinal barrier function by regulating intestinal flora, inhibiting renal fibrosis, and delaying the progression of chronic renal failure.}, }
@article {pmid38273106, year = {2024}, author = {Zhang, YD and Shi, DD and Liao, BB and Li, Y and Zhang, S and Gao, J and Lin, LJ and Wang, Z}, title = {Human microbiota from drug-naive patients with obsessive-compulsive disorder drives behavioral symptoms and neuroinflammation via succinic acid in mice.}, journal = {Molecular psychiatry}, volume = {29}, number = {6}, pages = {1782-1797}, pmid = {38273106}, issn = {1476-5578}, support = {82071518//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32271066//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2021-01-07-00-02-E0086//Shanghai Municipal Education Commission/ ; }, mesh = {Animals ; *Obsessive-Compulsive Disorder/metabolism/microbiology ; *Gastrointestinal Microbiome/physiology ; Mice ; Humans ; Male ; *Succinic Acid/metabolism ; *Disease Models, Animal ; *Fecal Microbiota Transplantation/methods ; Female ; Neuroinflammatory Diseases/metabolism ; Feces/microbiology ; Adult ; Behavioral Symptoms/metabolism ; Inflammation/metabolism ; Prefrontal Cortex/metabolism ; Anxiety/metabolism/microbiology ; Mice, Inbred C57BL ; Behavior, Animal ; Brain/metabolism ; Brain-Gut Axis/physiology ; }, abstract = {Emerging evidence suggests that the gut microbiota is closely related to psychiatric disorders. However, little is known about the role of the gut microbiota in the development of obsessive-compulsive disorder (OCD). Here, to investigate the contribution of gut microbiota to the pathogenesis of OCD, we transplanted fecal microbiota from first-episode, drug-naive OCD patients or demographically matched healthy individuals into antibiotic-treated specific pathogen-free (SPF) mice and showed that colonization with OCD microbiota is sufficient to induce core behavioral deficits, including abnormal anxiety-like and compulsive-like behaviors. The fecal microbiota was analyzed using 16 S rRNA full-length sequencing, and the results demonstrated a clear separation of the fecal microbiota of mice colonized with OCD and control microbiota. Notably, microbiota from OCD-colonized mice resulted in injured neuronal morphology and function in the mPFC, with inflammation in the mPFC and colon. Unbiased metabolomic analyses of the serum and mPFC region revealed the accumulation of succinic acid (SA) in OCD-colonized mice. SA impeded neuronal activity and induced an inflammatory response in both the colon and mPFC, impacting intestinal permeability and brain function, which act as vital signal mediators in gut microbiota-brain-immune crosstalk. Manipulations of dimethyl malonate (DM) have been reported to exert neuroprotective effects by suppressing the oxidation of accumulated succinic acid, attenuating the downstream inflammatory response and neuronal damage, and can help to partly improve abnormal behavior and reduce neuroinflammation and intestinal inflammation in OCD-colonized mice. We propose that the gut microbiota likely regulates brain function and behaviors in mice via succinic acid signaling, which contributes to the pathophysiology of OCD through gut-brain crosstalk and may provide new insights into the treatment of this disorder.}, }
@article {pmid38272165, year = {2024}, author = {Do Nascimento, J and Palos Ladeiro, M and Bonnard, I and Gantzer, C and Boudaud, N and Lopes, C and Geffard, A}, title = {Assessing viral freshwater hazard using a toxicokinetic model and Dreissena polymorpha.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {344}, number = {}, pages = {123420}, doi = {10.1016/j.envpol.2024.123420}, pmid = {38272165}, issn = {1873-6424}, mesh = {Animals ; *Dreissena ; Toxicokinetics ; *Bivalvia ; Fresh Water/chemistry ; Water ; }, abstract = {The detection all pathogenic enteric viruses in water is expensive, time-consuming, and limited by numerous technical difficulties. Consequently, using reliable indicators such as F-specific RNA phages (FRNAPH) can be well adapted to assess the risk of viral contamination of fecal origin in surface waters. However, the variability of results inherent to the water matrix makes it difficult to use them routinely and to interpret viral risk. Spatial and temporal variability of surface waters can lead to underestimate this risk, in particular in the case of low loading. The use of bivalve mollusks as accumulating systems appears as a promising alternative, as recently highlighted with the freshwater mussel Dreissena polymorpha, but its capacity to accumulate and depurate FRNAPH needs to be better understood and described. The purpose of this study is to characterise the kinetics of accumulation and elimination of infectious FRNAPH by D. polymorpha in laboratory conditions, formalised by a toxico-kinetic (TK) mechanistic model. Accumulation and depuration experiments were performed at a laboratory scale to determine the relationship between the concentration of infectious FRNAPH in water and the concentration accumulated by D. polymorpha. The mussels accumulated infectious FRNAPH (3-5.4 × 10[4] PFU/g) in a fast and concentration-dependent way in only 48 h, as already recently demonstrated. The second exposure demonstrated that the kinetics of infectious FRNAPH depuration by D. polymorpha was independent to the exposure dose, with a T90 (time required to depurate 90 % of the accumulated concentration) of approximately 6 days. These results highlight the capacities of D. polymorpha to detect and reflect the viral pollution in an integrative way and over time, which is not possible with point water sampling. Different TK models were fitted based on the concentrations measured in the digestive tissues (DT) of D. polymorpha. The model has been developed to formalise the kinetics of phage accumulation in mussels tissues through the simultaneous estimation of accumulation and depuration rates. This model showed that accumulation depended on the exposure concentration, while depuration did not. Standardized D. polymorpha could be easily transplanted to the environment to predict viral concentrations using the TK model defined in the present study to predict the level of contamination of bodies of water on the basis of the level of phages accumulated by the organisms. It will be also provide a better understanding of the dynamics of the virus in continental waters at different time and spatial scales, and thereby contribute to the protection of freshwater resources.}, }
@article {pmid38268839, year = {2024}, author = {Wu, J and Deng, X and Sun, Y and Li, J and Dai, H and Qi, S and Huang, Y and Sun, W}, title = {Aged oolong tea alleviates dextran sulfate sodium-induced colitis in mice by modulating the gut microbiota and its metabolites.}, journal = {Food chemistry: X}, volume = {21}, number = {}, pages = {101102}, pmid = {38268839}, issn = {2590-1575}, abstract = {In this study, the mechanism of aged oolong tea (AOT) to alleviate colitis was investigated in terms of microbiome, metabolome, and fecal microbiota transplantation (FMT). AOT storage period could alleviate colitis in mice and there were some differences in AOT between storage periods, especially AOT-10. AOT improves UC by modulating oxidative stress and inflammatory factors and upregulating intestinal tight junction protein expression (Occludin, Claudin-1, ZO-1 and MUC2), which is associated with the recovery of gut microbiota. FMT and targeted metabolomics further demonstrate that the anti-inflammatory effects of AOT can reshape the gut microbiota through faecal bacterial transfer. Anti-inflammatory effects are exerted through the stimulation of metabolic pathways associated with amino acid, fatty acid and bile acid metabolites. Importantly, the study identified key bacteria (e.g., Sutterella, Clostridiaceae_Clostridium, Mucispirillum, Oscillospira and Ruminococcus) for the development and remission of inflammation. Conclusively, AOT may have great potential in the future adjuvant treatment of colitis.}, }
@article {pmid38266859, year = {2024}, author = {Hu, H and Sun, W and Zhang, L and Zhang, Y and Kuang, T and Qu, D and Lian, S and Hu, S and Cheng, M and Xu, Y and Liu, S and Qian, Y and Lu, Y and He, L and Cheng, Y and Si, H}, title = {Carboxymethylated Abrus cantoniensis polysaccharide prevents CTX-induced immunosuppression and intestinal damage by regulating intestinal flora and butyric acid content.}, journal = {International journal of biological macromolecules}, volume = {261}, number = {Pt 1}, pages = {129590}, doi = {10.1016/j.ijbiomac.2024.129590}, pmid = {38266859}, issn = {1879-0003}, mesh = {Mice ; Animals ; Butyric Acid ; *Abrus ; *Gastrointestinal Microbiome ; Immunosuppression Therapy ; Intestines ; Polysaccharides/pharmacology ; }, abstract = {As a Chinese folk health product, Abrus cantoniensis exhibits good immunomodulatory activity because of its polysaccharide components (ACP), and carboxymethylation of polysaccharides can often further improve the biological activity of polysaccharides. In this study, we explored the impact of prophylactic administration of carboxymethylated Abrus cantoniensis polysaccharide (CM-ACP) on immunosuppression and intestinal damage induced by cyclophosphamide (CTX) in mice. Our findings demonstrated that CM-ACP exhibited a more potent immunomodulatory activity compared to ACP. Additionally, CM-ACP effectively enhanced the abundance of short-chain fatty acid (SCFA)-producing bacteria in immunosuppressed mice and regulated the gene expression of STAT6 and STAT3 mediated pathway signals. In order to further explore the relationship among polysaccharides, intestinal immunity and intestinal flora, we performed a pseudo-sterile mouse validation experiment and fecal microbiota transplantation (FMT) experiment. The findings suggest that CM-FMT and butyrate attenuate CTX-induced immunosuppression and intestinal injury. CM-FMT and butyrate show superior immunomodulatory ability, and may effectively regulate intestinal cell metabolism and repair the damaged intestine by activating STAT6 and STAT3-mediated pathways. These findings offer new insights into the mechanisms by which CM-ACP functions as functional food or drug, facilitating immune response regulation and maintaining intestinal health.}, }
@article {pmid38260901, year = {2023}, author = {Song, J and Luo, C and Liu, Z and Liu, J and Xie, L and Zhang, X and Xie, Z and Li, X and Ma, Z and Ding, J and Li, H and Xiang, H}, title = {Early fecal microbiota transplantation from high abdominal fat chickens affects recipient cecal microbiome and metabolism.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1332230}, pmid = {38260901}, issn = {1664-302X}, abstract = {Abdominal fat deposition (AFD) in chickens is closely related to the gut microecological balance. In this study, the gut microbiota from high-AFD chickens was transplanted into the same strain of 0-day-old chicks via fecal microbiota transplantation (FMT). The FTM from chickens with high AFD had no obvious effects on growth traits, adult body weight, carcass weight, abdominal fat weight, and abdominal fat percentage, but did reduce the coefficient of variation of AFD traits. FMT significantly decreased cecal microbiome richness, changed the microbiota structure, and regulated the biological functions associated with energy metabolism and fat synthesis. Additionally, the cecal metabolite composition and metabolic function of FMT recipient chickens were also significantly altered from those of the controls. Transplantation of high-AFD chicken gut microbiota promoted fatty acid elongation and biosynthesis and reduced the metabolism of vitamins, steroids, and carbohydrates in the cecum. These findings provide insights into the mechanisms by which chicken gut microbiota affect host metabolic profiles and fat deposition.}, }
@article {pmid38260539, year = {2024}, author = {Liu, C and Cyphert, EL and Stephen, SJ and Wang, B and Morales, AL and Nixon, JC and Natsoulas, NR and Garcia, M and Blazquez Carmona, P and Vill, AC and Donnelly, EL and Brito, IL and Vashishth, D and Hernandez, CJ}, title = {Microbiome-induced Increases and Decreases in Bone Tissue Strength can be Initiated After Skeletal Maturity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38260539}, issn = {2692-8205}, support = {F32 AG076244/AG/NIA NIH HHS/United States ; R01 AG067997/AG/NIA NIH HHS/United States ; S10 OD025049/OD/NIH HHS/United States ; }, abstract = {Recent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16 weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n=143 total, n=12-17/group/sex) were allocated into five study groups:1) Unaltered, 2) Continuous (dosing 4-24 weeks of age), 3) Delayed (dosing only 16-24 weeks of age), 4) Initial (dosing 4-16 weeks of age, suspended at 16 weeks), and 5) Reconstituted (dosing from 4-16 weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24 weeks of age. In males, bone matrix strength in the femur was 25-35% less than expected from geometry in mice from the Continuous (p= 0.001), Delayed (p= 0.005), and Initial (p=0.040) groups as compared to Unaltered. Reconstitution of the gut microbiota, however, led to a bone matrix strength similar to Unaltered animals (p=0.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating sex-related differences in the response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed (Raman spectroscopy). Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16 weeks) is small; however, this suggests that microbiome-induced changes in bone matrix occur without osteoblast/osteoclast turnover using an, as of yet unidentified mechanism. These findings add to evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.}, }
@article {pmid38260015, year = {2023}, author = {Mogi, K and Akiyama, U and Futagawa, N and Tamura, K and Kamiya, M and Mizuta, M and Yamaoka, M and Kamimura, I and Kuze-Arata, S and Kikusui, T}, title = {Intergenerational transmission of maternal behavioral traits in mice: involvement of the gut microbiota.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1302841}, pmid = {38260015}, issn = {1662-4548}, abstract = {The matrilineal transmission of maternal behavior has been reported in several species. Studies, primarily on rats, have suggested the importance of postnatal experience and the involvement of epigenetic mechanisms in mediating these transmissions. This study aims to determine whether the matrilineal transmission of maternal behavior occurs in mice and whether the microbiota is involved. We first observed that early weaned (EW) female mice showed lower levels of maternal behavior, particularly licking/grooming (LG) of their own pups, than normally weaned (NW) female mice. This difference in maternal behavioral traits was also observed in the second generation, even though all mice were weaned normally. In the subsequent cross-fostering experiment, the levels of LG were influenced by the nurturing mother but not the biological mother. Finally, we transplanted the fecal microbiota from EW or NW mice into germ-free (GF) mice raising pups. The maternal behaviors that the pups exhibited toward their own offspring after growth were analyzed, and the levels of LG in GF mice colonized with microbiota from EW mice were lower than those in GF mice colonized with microbiota from NW mice. These results clearly indicate that, among maternal behavioral traits, LG is intergenerationally transmitted in mice and suggest that the vertical transmission of microbiota is involved in this process. This study demonstrates the universality of the intergenerational transmission of maternal behavioral traits and provides new insights into the role of microbiota.}, }
@article {pmid38259389, year = {2023}, author = {Ghazanfar, H and Kandhi, S and Acherjee, T and Qureshi, ZA and Shaban, M and Yordanka, DS and Cordero, D and Chinta, S and Jyala, A and Patel, H}, title = {Role of Fecal Microbiota Transplantation in Managing Clostridium Difficile Infection and Inflammatory Bowel Disease: A Narrative Review.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e51004}, pmid = {38259389}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) has been emerging as an alternate treatment modality in the management of patients with dysbiosis by restoring abnormal gut microbiota composition through the transplantation of normal fecal microbiota from healthy donors. This technique has lately gained a lot of attention in the treatment of recurrent or refractory Clostridium difficile infection (CDI) owing to its high success rates combined with its favorable safety profile. FMT has also been attracting the interest of clinicians as a new treatment option for inflammatory bowel diseases (IBD). Here, we reviewed most of the recent advancements in the use of FMT for CDI as well as its use in the treatment of IBD.}, }
@article {pmid38257851, year = {2023}, author = {Ciernikova, S and Sevcikova, A and Mladosievicova, B and Mego, M}, title = {Microbiome in Cancer Development and Treatment.}, journal = {Microorganisms}, volume = {12}, number = {1}, pages = {}, pmid = {38257851}, issn = {2076-2607}, support = {No. 2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; No. 1/0738/21//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, abstract = {Targeting the microbiome, microbiota-derived metabolites, and related pathways represents a significant challenge in oncology. Microbiome analyses have confirmed the negative impact of cancer treatment on gut homeostasis, resulting in acute dysbiosis and severe complications, including massive inflammatory immune response, mucosal barrier disruption, and bacterial translocation across the gut epithelium. Moreover, recent studies revealed the relationship between an imbalance in the gut microbiome and treatment-related toxicity. In this review, we provide current insights into the role of the microbiome in tumor development and the impact of gut and tumor microbiomes on chemo- and immunotherapy efficacy, as well as treatment-induced late effects, including cognitive impairment and cardiotoxicity. As discussed, microbiota modulation via probiotic supplementation and fecal microbiota transplantation represents a new trend in cancer patient care, aiming to increase bacterial diversity, alleviate acute and long-term treatment-induced toxicity, and improve the response to various treatment modalities. However, a more detailed understanding of the complex relationship between the microbiome and host can significantly contribute to integrating a microbiome-based approach into clinical practice. Determination of causal correlations might lead to the identification of clinically relevant diagnostic and prognostic microbial biomarkers. Notably, restoration of intestinal homeostasis could contribute to optimizing treatment efficacy and improving cancer patient outcomes.}, }
@article {pmid38256945, year = {2024}, author = {Kim, SJ and Park, M and Choi, A and Yoo, S}, title = {Microbiome and Prostate Cancer: Emerging Diagnostic and Therapeutic Opportunities.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {1}, pages = {}, pmid = {38256945}, issn = {1424-8247}, support = {Project No: 20016285//Technology Innovation Pro-398 gram funded by the Ministry of Trade, Industry and Energy (MOTIE)/ ; 2022RIS-005//"Regional Innovation Strategy (RIS)" through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) in 2023/ ; }, abstract = {This review systematically addresses the correlation between the microbiome and prostate cancer and explores its diagnostic and therapeutic implications. Recent research has indicated an association between the urinary and gut microbiome composition and prostate cancer incidence and progression. Specifically, the urinary microbiome is a potential non-invasive biomarker for early detection and risk evaluation, with altered microbial profiles in prostate cancer patients. This represents an advancement in non-invasive diagnostic approaches to prostate cancer. The role of the gut microbiome in the efficacy of various cancer therapies has recently gained attention. Gut microbiota variations can affect the metabolism and effectiveness of standard treatment modalities, including chemotherapy, immunotherapy, and hormone therapy. This review explores the potential of gut microbiome modification through dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation for improving the treatment response and mitigating adverse effects. Moreover, this review discusses the potential of microbiome profiling for patient stratification and personalized treatment strategies. While the current research identifies the pivotal role of the microbiome in prostate cancer, it also highlights the necessity for further investigations to fully understand these complex interactions and their practical applications in improving patient outcomes in prostate cancer management.}, }
@article {pmid38255326, year = {2024}, author = {Clemente-Suárez, VJ and Redondo-Flórez, L and Rubio-Zarapuz, A and Martín-Rodríguez, A and Tornero-Aguilera, JF}, title = {Microbiota Implications in Endocrine-Related Diseases: From Development to Novel Therapeutic Approaches.}, journal = {Biomedicines}, volume = {12}, number = {1}, pages = {}, pmid = {38255326}, issn = {2227-9059}, abstract = {This comprehensive review article delves into the critical role of the human microbiota in the development and management of endocrine-related diseases. We explore the complex interactions between the microbiota and the endocrine system, emphasizing the implications of microbiota dysbiosis for the onset and progression of various endocrine disorders. The review aims to synthesize current knowledge, highlighting recent advancements and the potential of novel therapeutic approaches targeting microbiota-endocrine interactions. Key topics include the impact of microbiota on hormone regulation, its role in endocrine pathologies, and the promising avenues of microbiota modulation through diet, probiotics, prebiotics, and fecal microbiota transplantation. We underscore the importance of this research in advancing personalized medicine, offering insights for more tailored and effective treatments for endocrine-related diseases.}, }
@article {pmid38255161, year = {2023}, author = {Li, J and Liu, Y and Li, Y and Sun, T and Xiang, H and He, Z}, title = {The Role of Gut Microbiota and Circadian Rhythm Oscillation of Hepatic Ischemia-Reperfusion Injury in Diabetic Mice.}, journal = {Biomedicines}, volume = {12}, number = {1}, pages = {}, pmid = {38255161}, issn = {2227-9059}, support = {82070302,81873467//National Natural Science Foundation of China/ ; }, abstract = {Circadian rhythm oscillation and the gut microbiota play important roles in several physiological functions and pathology regulations. In this study, we aimed to elucidate the characteristics of diabetic hepatic ischemia-reperfusion injury (HIRI) and the role of the intestinal microbiota in diabetic mice with HIRI. Hepatic ischemia-reperfusion injury surgery was performed at ZT0 or ZT12. The liver pathological score and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed to evaluate liver injury. We conducted an FMT experiment to examine the role of intestinal microbiota in diabetic mice with HIRI. The 16S rRNA gene sequencing of fecal samples was performed for microbial analysis. Our results showed that hyperglycemia aggravated HIRI in diabetic mice, but there was no diurnal variation seen in diabetic HIRI. We also demonstrated that there were significant alterations in the gut microbiota composition between the diabetic and control mice and that gut microbiota transplantation from diabetic mice had obvious harmful effects on HIRI. These findings provide some useful information for the future research of diabetic mice with HIRI.}, }
@article {pmid38255150, year = {2023}, author = {Lauko, S and Gancarcikova, S and Hrckova, G and Hajduckova, V and Andrejcakova, Z and Fecskeova, LK and Bertkova, I and Hijova, E and Kamlarova, A and Janicko, M and Ambro, L and Kvakova, M and Gulasova, Z and Strojny, L and Strkolcova, G and Mudronova, D and Madar, M and Demeckova, V and Nemetova, D and Pacuta, I and Sopkova, D}, title = {Beneficial Effect of Faecal Microbiota Transplantation on Mild, Moderate and Severe Dextran Sodium Sulphate-Induced Ulcerative Colitis in a Pseudo Germ-Free Animal Model.}, journal = {Biomedicines}, volume = {12}, number = {1}, pages = {}, pmid = {38255150}, issn = {2227-9059}, support = {APVV-16-0176//Slovak Research and Development Agency/ ; VEGA 1/0015/21//Ministry of Education of SR/ ; }, abstract = {Transplantation of faecal microbiota (FMT) is generally considered a safe therapeutic procedure with few adverse effects. The main factors that limit the spread of the use of FMT therapy for idiopathic inflammatory bowel disease (IBD) are the necessity of minimising the risk of infection and transfer of another disease. Obtaining the animal model of UC (ulcerative colitis) by exposure to DSS (dextran sodium sulphate) depends on many factors that significantly affect the result. Per os intake of DSS with water is individual for each animal and results in the development of a range of various forms of induced UC. For this reason, the aim of our study was to evaluate the modulation and regenerative effects of FMT on the clinical and histopathological responses and the changes in the bowel microenvironment in pseudo germ-free (PGF) mice of the BALB/c line subjected to chemical induction of mild, moderate and serious forms of UC. The goal was to obtain new data related to the safety and effectiveness of FMT that can contribute to its improved and optimised use. The animals with mild and moderate forms of UC subjected to FMT treatment exhibited lower severity of the disease and markedly lower damage to the colon, including reduced clinical and histological disease index and decreased inflammatory response of colon mucosa. However, FMT treatment failed to achieve the expected therapeutic effect in animals with the serious form of UC activity. The results of our study indicated a potential safety risk involving development of bacteraemia and also translocation of non-pathogenic representatives of bowel microbiota associated with FMT treatment of animals with a diagnosed serious form of UC.}, }
@article {pmid38254757, year = {2024}, author = {Oberhoff, G and Schooren, L and Vondran, F and Kroh, A and Koch, A and Bednarsch, J and Neumann, UP and Schmitz, SM and Alizai, PH}, title = {Impairment of Nutritional Status and Quality of Life Following Minimal-Invasive Esophagectomy-A Prospective Cohort Analysis.}, journal = {Cancers}, volume = {16}, number = {2}, pages = {}, pmid = {38254757}, issn = {2072-6694}, support = {START Grant//Universit&#xe4;tsklinikum Aachen/ ; }, abstract = {Minimal-invasive resection of the esophagus for esophageal cancer has led to a relevant decrease in postoperative morbidity. Postoperatively, patients still suffer from surgical and adjuvant therapy-related symptoms impairing nutrition and quality of life. The aim of this study was to evaluate the nutritional status and associated symptoms six months after esophagectomy. Patients who attended follow-up examination six months after minimal-invasive esophagectomy were included. Blood and fecal tests, quality of life surveys (QLQ-C30 and QLQ-OG25) and nutritional risk screening (NRS) were performed. Twenty-four patients participated. The mean weight loss was 11 kg. A significant decrease in vitamin B12 (737 to 467 pg/mL; p = 0.033), ferritin (302 to 126 ng/mL; p = 0.012) and haptoglobin (227 to 152 mg/dL; p = 0.025) was found. In total, 47% of the patients had an impaired pancreatic function (fecal elastase < 500 µg/g). Physical (72 to 58; p = 0.034) and social functioning (67 to 40; p = 0.022) was significantly diminished, while self-reported global health status remained stable (52 to 54). The number of patients screened and found to be in need of nutritional support according to NRS score decreased slightly (59% to 52%). After MIE, patients should be meticulously monitored for nutritional status after surgery.}, }
@article {pmid38254421, year = {2024}, author = {Leduc, L and Costa, M and Leclère, M}, title = {The Microbiota and Equine Asthma: An Integrative View of the Gut-Lung Axis.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {2}, pages = {}, pmid = {38254421}, issn = {2076-2615}, abstract = {Both microbe-microbe and host-microbe interactions can have effects beyond the local environment and influence immunological responses in remote organs such as the lungs. The crosstalk between the gut and the lungs, which is supported by complex connections and intricate pathways, is defined as the gut-lung axis. This review aimed to report on the potential role of the gut-lung gut-lung axis in the development and persistence of equine asthma. We summarized significant determinants in the development of asthma in horses and humans. The article discusses the gut-lung axis and proposes an integrative view of the relationship between gut microbiota and asthma. It also explores therapies for modulating the gut microbiota in horses with asthma. Improving our understanding of the horse gut-lung axis could lead to the development of techniques such as fecal microbiota transplants, probiotics, or prebiotics to manipulate the gut microbiota specifically for improving the management of asthma in horses.}, }
@article {pmid38253409, year = {2024}, author = {Zong, Y and Mao, T and Yao, P and Liang, J and Lai, Y and Chen, Z and Chen, S and Huang, L and Guo, Y and Zhu, M and Zhao, J and Liu, Y and Li, Y and Guo, K and Tang, H and Ke, X and Zhou, Y}, title = {Effects of Guizhi and Erxian Decoction on menopausal hot flashes: insights from the gut microbiome and metabolic profiles.}, journal = {Journal of applied microbiology}, volume = {135}, number = {4}, pages = {}, doi = {10.1093/jambio/lxae016}, pmid = {38253409}, issn = {1365-2672}, support = {2019IIT17//Guangzhou University of Chinese Medicine/ ; 202102010400//City School (hospital) joint funding project/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Hot Flashes/metabolism/drug therapy ; Rats ; Female ; *Drugs, Chinese Herbal/pharmacology ; *Menopause ; Fecal Microbiota Transplantation ; Ovariectomy ; Rats, Sprague-Dawley ; RNA, Ribosomal, 16S/genetics ; Metabolome/drug effects ; }, abstract = {AIMS: To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes.<br><br>METHODS AND RESULTS: 16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition.<br><br>CONCLUSIONS: Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.}, }
@article {pmid38250691, year = {2024}, author = {Homma, Y and Mimura, T and Koinuma, K and Horie, H and Lefor, AK and Sata, N}, title = {Low anterior resection syndrome: Incidence and association with quality of life.}, journal = {Annals of gastroenterological surgery}, volume = {8}, number = {1}, pages = {114-123}, pmid = {38250691}, issn = {2475-0328}, abstract = {AIM: Low anterior resection syndrome (LARS) causes devastating symptoms and impairs quality of life (QOL). Although its incidence and risk factors have been reported, these data are scarce in Japan. This study aimed to elucidate the incidence and risk factors of LARS as well as to evaluate its association with QOL in Japanese patients.<br><br>METHOD: Patients with anal defecation at the time of the survey between November 2020 and April 2021 were included, among those who underwent anus-preserving surgery for rectal tumors between 2014 and 2019 in tertiary referral university hospital. The severity of LARS and QOL were evaluated with the LARS score and the Japanese version of the fecal incontinence quality of life scale (JFIQL), respectively. Primary endpoint was the incidence of major LARS. Secondary endpoints were risk factors and association with JFIQL.<br><br>RESULTS: Of 332 eligible patients, 238 (71.7%) answered the LARS survey completely. The incidence of major LARS was 22% overall, and 48% when limited to lower tumors. Independent risk factors included lower tumors (OR: 7.0, 95% CI: 2.1-23.1, p&#x2009;=&#x2009;0.001) and surgical procedures with lower anastomoses (OR: 4.6, 95% CI: 1.2-18.5, p&#x2009;=&#x2009;0.03). The JFIQL generic score correlated moderately with the LARS score (correlation coefficient of -0.65). The JFIQL generic score was also significantly lower in lower tumors.<br><br>CONCLUSIONS: The incidence of major LARS is 22% in Japanese patients, and independent risk factors include lower tumors and surgical procedures with lower anastomoses. More severe LARS is associated with worse QOL which is significantly more impaired in patients with lower tumors.}, }
@article {pmid38250318, year = {2024}, author = {Kim, JS and Park, H and Lee, JH and Shin, J and Cha, B and Kwon, KS and Shin, YW and Kim, Y and Kim, Y and Bae, JS and Lee, JH and Choi, SJ and Kim, TJ and Ko, SB and Park, SH}, title = {Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer's dementia following fecal microbiota transplantation: a preliminary study.}, journal = {Therapeutic advances in neurological disorders}, volume = {17}, number = {}, pages = {17562864231218181}, pmid = {38250318}, issn = {1756-2856}, abstract = {BACKGROUND: The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement.<br><br>OBJECTIVE: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT.<br><br>METHODS: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction.<br><br>RESULTS: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3&#x2009;months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT.<br><br>CONCLUSION: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.}, }
@article {pmid38249807, year = {2024}, author = {Jiang, H and Zhang, Q}, title = {Gut microbiota influences the efficiency of immune checkpoint inhibitors by modulating the immune system (Review).}, journal = {Oncology letters}, volume = {27}, number = {2}, pages = {87}, pmid = {38249807}, issn = {1792-1082}, abstract = {Immune checkpoint inhibitors (ICIs) are commonly utilized in tumor treatment. However, they still have limitations, including insufficient effectiveness and unavoidable adverse events. It has been demonstrated that gut microbiota can influence the effectiveness of ICIs, although the precise mechanism remains unclear. Gut microbiota plays a crucial role in the formation and development of the immune system. Gut microbiota and their associated metabolites play a regulatory role in immune balance. Tumor occurrence and development are linked to their ability to evade recognition and destruction by the immune system. The purpose of ICIs treatment is to reinitiate the immune system's elimination of tumor cells. Thus, the immune system acts as a communication bridge between gut microbiota and ICIs. Varied composition and characteristics of gut microbiota result in diverse outcomes in ICIs treatment. Certain gut microbiota-related metabolites also influence the therapeutic efficacy of ICIs to some extent. The administration of antibiotics before or during ICIs treatment can diminish treatment effectiveness. The utilization of probiotics and fecal transplantation can partially alter the outcome of ICIs treatment. The present review synthesized previous studies to examine the association between gut microbiota and ICIs, elucidated the role of gut microbiota and its associated factors in ICIs treatment, and offered direction for future research.}, }
@article {pmid38249454, year = {2023}, author = {Li, D and Liang, W and Zhang, W and Huang, Z and Liang, H and Liu, Q}, title = {Fecal microbiota transplantation repairs intestinal permeability and regulates the expression of 5-HT to influence alcohol-induced depression-like behaviors in C57BL/6J mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1241309}, pmid = {38249454}, issn = {1664-302X}, abstract = {The epidemic of alcohol abuse affects millions of people worldwide. Relevant evidence supports the notion that the gut microbiota (GM) plays a crucial role in central nervous system (CNS) function, and its composition undergoes changes following alcohol consumption. Therefore, the purpose of this study was to investigate the effect of reconstructing the gut microbiota by fecal microbiota transplantation (FMT) on alcohol dependence. Here, we established an alcohol dependence model with C57BL/6J mice and proved that FMT treatment improved anxiety-like behavior and alcohol-seeking behavior in alcohol-dependent mice. Additionally, we found that the expression of the intestinal intercellular tight junction structure proteins ZO-1 and occludin was significantly increased after FMT. FMT repaired intestinal permeability in alcohol-dependent mice and decreased the levels of lipopolysaccharide (LPS) and proinflammatory factors. Moreover, the serotonin (5-hydroxytryptamine, 5-HT) content was significantly increased in alcohol-dependent mouse intestinal and brain tissues after receiving the fecal microbiome from healthy mice. 16S rRNA sequencing demonstrated that FMT markedly reshaped the composition of the gut microbiota and elicited changes in the intestinal barrier and 5-HT levels. Collectively, our results revealed that FMT has a palliative effect on alcohol dependence and explored the underlying mechanisms, which provides new strategies for the treatment of alcohol dependence.}, }
@article {pmid38249228, year = {2023}, author = {Bhattacharjee, P and Karim, KA and Khan, Z}, title = {Harnessing the Microbiome: A Comprehensive Review on Advancing Therapeutic Strategies for Rheumatic Diseases.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50964}, pmid = {38249228}, issn = {2168-8184}, abstract = {Rheumatic diseases are a group of disorders that affect the joints, muscles, and bones. These diseases, such as rheumatoid arthritis, lupus, and psoriatic arthritis, can cause pain, stiffness, and swelling, leading to reduced mobility and disability. Recent studies have identified the microbiome, the diverse community of microorganisms that live in and on the human body, as a potential factor in the development and progression of rheumatic diseases. Harnessing the microbiome offers a promising new avenue for developing therapeutic strategies for these debilitating conditions. There is growing interest in the role of oral and gut microbiomes in the management of rheumatoid arthritis and other autoimmune disease. Microbial metabolites have immunomodulatory properties that could be exploited for rheumatic disorders. A wide range of microorganisms are present in the oral cavity and are found to be vulnerable to the effects of the environment. The physiology and ecology of the microbiota become intimately connected with those of the host, and they critically influence the promotion of health or progression toward disease. This article aims to provide a comprehensive overview of the current state of knowledge on oral and gut microbiome and its potential future role in the management of rheumatic diseases. This article will also discuss newer treatment strategies such as bioinformatic analyses and fecal transplantation.}, }
@article {pmid38247148, year = {2024}, author = {Taha, AS}, title = {Editorial: The microbiome and gastric mucosal protection in aspirin users.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {59}, number = {4}, pages = {575-576}, doi = {10.1111/apt.17821}, pmid = {38247148}, issn = {1365-2036}, mesh = {Humans ; *Microbiota ; *Aspirin/adverse effects ; *Gastric Mucosa/drug effects ; }, }
@article {pmid38244075, year = {2024}, author = {Yuan, L and Li, Y and Chen, M and Xue, L and Wang, J and Ding, Y and Gu, Q and Zhang, J and Zhao, H and Xie, X and Wu, Q}, title = {Therapeutic applications of gut microbes in cardiometabolic diseases: current state and perspectives.}, journal = {Applied microbiology and biotechnology}, volume = {108}, number = {1}, pages = {156}, pmid = {38244075}, issn = {1432-0614}, support = {2021YFA0910200//Guangdong Province National key research and development project/ ; 2022B1111070006//Guangdong Province key research and development project/ ; 2020GDASYL20200102003//Innovation Development Project of Guangdong Academy of Sciences/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/therapy ; Diet ; *Microbiota ; *Heart Failure ; }, abstract = {Cardiometabolic disease (CMD) encompasses a range of diseases such as hypertension, atherosclerosis, heart failure, obesity, and type 2 diabetes. Recent findings about CMD's interaction with gut microbiota have broadened our understanding of how diet and nutrition drive microbes to influence CMD. However, the translation of basic research into the clinic has not been smooth, and dietary nutrition and probiotic supplementation have yet to show significant evidence of the therapeutic benefits of CMD. In addition, the published reviews do not suggest the core microbiota or metabolite classes that influence CMD, and systematically elucidate the causal relationship between host disease phenotypes-microbiome. The aim of this review is to highlight the complex interaction of the gut microbiota and their metabolites with CMD progression and to further centralize and conceptualize the mechanisms of action between microbial and host disease phenotypes. We also discuss the potential of targeting modulations of gut microbes and metabolites as new targets for prevention and treatment of CMD, including the use of emerging technologies such as fecal microbiota transplantation and nanomedicine. KEY POINTS: • To highlight the complex interaction of the gut microbiota and their metabolites with CMD progression and to further centralize and conceptualize the mechanisms of action between microbial and host disease phenotypes. • We also discuss the potential of targeting modulations of gut microbes and metabolites as new targets for prevention and treatment of CMD, including the use of emerging technologies such as FMT and nanomedicine. • Our study provides insight into identification-specific microbiomes and metabolites involved in CMD, and microbial-host changes and physiological factors as disease phenotypes develop, which will help to map the microbiome individually and capture pathogenic mechanisms as a whole.}, }
@article {pmid38243335, year = {2024}, author = {Han, Y and Zeng, X and Hua, L and Quan, X and Chen, Y and Zhou, M and Chuang, Y and Li, Y and Wang, S and Shen, X and Wei, L and Yuan, Z and Zhao, Y}, title = {The fusion of multi-omics profile and multimodal EEG data contributes to the personalized diagnostic strategy for neurocognitive disorders.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {12}, pmid = {38243335}, issn = {2049-2618}, support = {0106/2019/A2//Science and Technology Development Fund, Macau SAR/ ; MYRG-CRG2022-00011-ICMS//University of Macau/ ; }, mesh = {Humans ; Animals ; Mice ; Aged ; *Multiomics ; *Proteomics/methods ; Metagenomics/methods ; Metabolomics/methods ; Electroencephalography/methods ; }, abstract = {BACKGROUND: The increasing prevalence of neurocognitive disorders (NCDs) in the aging population worldwide has become a significant concern due to subjectivity of evaluations and the lack of precise diagnostic methods and specific indicators. Developing personalized diagnostic strategies for NCDs has therefore become a priority.<br><br>RESULTS: Multimodal electroencephalography (EEG) data of a matched cohort of normal aging (NA) and NCDs seniors were recorded, and their faecal samples and urine exosomes were collected to identify multi-omics signatures and metabolic pathways in NCDs by integrating metagenomics, proteomics, and metabolomics analysis. Additionally, experimental verification of multi-omics signatures was carried out in aged mice using faecal microbiota transplantation (FMT). We found that NCDs seniors had low EEG power spectral density and identified specific microbiota, including Ruminococcus gnavus, Enterocloster bolteae, Lachnoclostridium sp. YL 32, and metabolites, including L-tryptophan, L-glutamic acid, gamma-aminobutyric acid (GABA), and fatty acid esters of hydroxy fatty acids (FAHFAs), as well as disturbed biosynthesis of aromatic amino acids and TCA cycle dysfunction, validated in aged mice. Finally, we employed a support vector machine (SVM) algorithm to construct a machine learning model to classify NA and NCDs groups based on the fusion of EEG data and multi-omics profiles and the model demonstrated 92.69% accuracy in classifying NA and NCDs groups.<br><br>CONCLUSIONS: Our study highlights the potential of multi-omics profiling and EEG data fusion in personalized diagnosis of NCDs, with the potential to improve diagnostic precision and provide insights into the underlying mechanisms of NCDs. Video Abstract.}, }
@article {pmid38242462, year = {2024}, author = {Feng, Y and Wu, H and Feng, L and Zhang, R and Feng, X and Wang, W and Xu, H and Fu, F}, title = {Maternal F-53B exposure during pregnancy and lactation induced glucolipid metabolism disorders and adverse pregnancy outcomes by disturbing gut microbiota in mice.}, journal = {The Science of the total environment}, volume = {915}, number = {}, pages = {170130}, doi = {10.1016/j.scitotenv.2024.170130}, pmid = {38242462}, issn = {1879-1026}, mesh = {Humans ; Mice ; Pregnancy ; Female ; Animals ; Pregnancy Outcome ; *Gastrointestinal Microbiome ; Lactation ; Inflammation ; *Metabolic Diseases ; }, abstract = {In the metal plating industry, F-53B has been widely used for almost half a century as a replacement for perfluorooctane sulfonate. However, F-53B can reach the food chain and affect human health. Pregnant women have distinct physiological characteristics and may thus be more sensitive to the toxicity of F-53B. In the present study, F-53B was added to the drinking water of pregnant mice during gestation and lactation at doses of 0 mg/L (Ctrl), 0.57 mg/L (L-F), and 5.7 mg/L (H-F). The aim was to explore the potential effects of F-53B on glucolipid metabolism and pregnancy outcomes in dams. Results showed that F-53B induced disordered glucolipid metabolism, adverse pregnancy outcomes, hepatic inflammation, oxidative stress and substantially altered related biochemical parameters in maternal mice. Moreover, F-53B induced remarkable gut barrier damage and gut microbiota perturbation. Correlation analysis revealed that gut microbiota is associated with glucolipid metabolism disorders and hepatic inflammation. The fecal microbiota transplant experiment demonstrated that altered gut microbiota induced by F-53B caused metabolic disorders, adverse pregnancy outcomes, and gut barrier damage. These results suggested that maternal mice exposed to F-53B during gestation and lactation had an increased risk of developing metabolic disorders and adverse pregnancy outcomes and highlighted the crucial role of the gut microbiota in this process, offering novel insights into the risk of F-53B to health.}, }
@article {pmid38241975, year = {2024}, author = {Yang, Y and An, Y and Dong, Y and Chu, Q and Wei, J and Wang, B and Cao, H}, title = {Fecal microbiota transplantation: no longer cinderella in tumour immunotherapy.}, journal = {EBioMedicine}, volume = {100}, number = {}, pages = {104967}, pmid = {38241975}, issn = {2352-3964}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Microbiota ; *Gastrointestinal Microbiome ; *Neoplasms/therapy ; Immunotherapy ; Tumor Microenvironment ; }, abstract = {The incidence of cancer has shown a great increase during the past decades and poses tough challenges to cancer treatment. Anti-tumour immunotherapy, represented by immune checkpoint inhibitors (ICIs), possesses favorable remission in unrestricted spectrum of cancer types. However, its efficacy seems to be heterogeneous among accumulating studies. Emerging evidences suggest that gut microbiota can modulate anti-tumour immuno-response and predict clinical prognosis. Therefore, remodeling microbiota characteristics with fecal microbiota transplantation (FMT) may be capable of reinforcing host ICIs performance by regulating immune-tumour cell interactions and altering microbial metabolites, thereby imperceptibly shifting the tumour microenvironment. However, the long-term safety of FMT is under concern, which calls for more rigorous screening. In this review, we examine current experimental and clinical evidences supporting the FMT efficacy in boosting anti-tumour immuno-response and lessening tumour-related complications. Moreover, we discuss the challenges in FMT and propose feasible resolutions, which may offer crucial guidance for future clinical operations.}, }
@article {pmid38241896, year = {2024}, author = {Tyszka, M and Maciejewska-Markiewicz, D and Styburski, D and Biliński, J and Tomaszewska, A and Stachowska, E and Basak, GW}, title = {Altered lipid metabolism in patients with acute graft-versus-host disease after allogeneic hematopoietic cell transplantation.}, journal = {Leukemia research}, volume = {137}, number = {}, pages = {107435}, doi = {10.1016/j.leukres.2024.107435}, pmid = {38241896}, issn = {1873-5835}, mesh = {Humans ; Lipid Metabolism ; Prospective Studies ; *Graft vs Host Disease/etiology/prevention &amp; control ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Bile Acids and Salts ; Cholesterol ; Acute Disease ; }, abstract = {Allogeneic hematopoietic cell transplantation (allo-HCT) remains the sole curative option for many hematological malignancies and other diseases. Nevertheless, its application is limited due to the risk of life-threatening complications, mainly graft-versus-host disease (GVHD). Currently, in clinical practice, the risk of developing GVHD is estimated for every patient based on factors related to the donor and the host. In our prospective, observational study, we analyzed serum from 38 patients undergoing allo-HCT at our institution. We compared the metabolic profiles of patients who developed acute GVHD (aGVHD) with those without such complication by identification and comparison of metabolites masses on the XCMS platform. We observed that patients diagnosed with aGVHD had different metabolic profiles compared to the remaining patients and this alteration was noticeable already 7 days before the procedure. We identified dysregulated metabolites involved in bile acid transformation and cholesterol synthesis. Our study of the untargeted metabolome in allo-HCT recipients has revealed a potential link between lipid metabolism, specifically involving bile acid transformation and cholesterol synthesis, and the development of aGVHD. This finding might be an important indication for future research focused on understanding GVHD development, discovering prediction models, and investigating possible prophylactic interventions.}, }
@article {pmid38238900, year = {2024}, author = {Yan, H and Zhang, Y and Lin, X and Huang, J and Zhang, F and Chen, C and Ren, H and Zheng, S and Yang, J and Hui, S}, title = {Resveratrol improves diabetic kidney disease by modulating the gut microbiota-short chain fatty acids axis in db/db mice.}, journal = {International journal of food sciences and nutrition}, volume = {75}, number = {3}, pages = {264-276}, doi = {10.1080/09637486.2024.2303041}, pmid = {38238900}, issn = {1465-3478}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Fatty Acids, Volatile/metabolism ; *Diabetic Nephropathies/drug therapy ; *Resveratrol/pharmacology ; Mice ; Male ; Fibrosis ; Feces/microbiology ; Dysbiosis ; Kidney/drug effects ; Mice, Inbred C57BL ; }, abstract = {Diabetic kidney disease is associated with the dysbiosis of the gut microbiota and its metabolites. db/db mice were fed chow diet with or without 0.4% resveratrol for 12 weeks, after which the gut microbiota, faecal short-chain fatty acids (SCFAs), and renal fibrosis were analysed. Resveratrol ameliorated the progression of diabetic kidney disease and alleviated tubulointerstitial fibrosis. Further studies showed that gut microbiota dysbiosis was modulated by resveratrol, characterised by the expansion of SCFAs-producing bacteria Faecalibaculum and Lactobacillus, which increased the concentrations of SCFAs (especially acetic acid) in the faeces. Moreover, microbiota transplantation experiments found that alteration of the gut microbiota contributed to the prevention of diabetic kidney disease. Acetate treatment ameliorated proteinuria, glomerulosclerosis and tubulointerstitial fibrosis in db/db mice. Overall, resveratrol improved the progression of diabetic kidney disease by suppressing tubulointerstitial fibrosis, which may be involved, at least in part, in the regulation of the gut microbiota-SCFAs axis.}, }
@article {pmid38237167, year = {2024}, author = {Guo, L and Liu, Q and Yin, X}, title = {Gut Microbiota Protects Listeria monocytogenes-Infected Mice by Reducing the Inflammatory Cytokines Storm and Cell Apoptosis.}, journal = {Foodborne pathogens and disease}, volume = {21}, number = {5}, pages = {288-297}, doi = {10.1089/fpd.2023.0121}, pmid = {38237167}, issn = {1556-7125}, mesh = {Animals ; *Listeriosis/microbiology/immunology ; *Gastrointestinal Microbiome ; *Listeria monocytogenes ; *Apoptosis ; Mice ; *Fecal Microbiota Transplantation ; *Cytokines/metabolism ; Humans ; Caco-2 Cells ; Liver/microbiology ; Spleen/microbiology ; Female ; }, abstract = {Gut microbiota (GM) has been proven to resist pathogenic infection through nutritional competition, colonization resistance and promotion of the host immune response. However, in clinical practice, GM is mainly used in intestinal diseases, such as Clostridium difficile infection, and there are few reports on its application in the treatment of pathogenic bacterial infections. In this study, GM from healthy mice was transplanted into mice infected with Listeria monocytogenes using fecal microbiota transplantation (FMT) and the effects were observed. We found that GM from healthy mice could reduce the mortality of infected mice and decrease the counts of L. monocytogenes in their liver and spleen. In addition, FMT inhibited the expression of inflammatory factors in the liver and spleen of infected mice. In vitro cell experiments revealed that GM can reduce the count of L. monocytogenes invading Caco-2 cells and inhibit the L. monocytogenes-caused apoptosis. These results indicate that GM can be used to protect mice infected with L. monocytogenes by eliminating the amount of L. monocytogenes in the host and inhibiting the overexpression of inflammatory factors. Hence, this method can potentially replace antibiotics in the treatment of L. monocytogenes infection.}, }
@article {pmid38232140, year = {2024}, author = {Bhattarai, SK and Du, M and Zeamer, AL and M Morzfeld, B and Kellogg, TD and Firat, K and Benjamin, A and Bean, JM and Zimmerman, M and Mardi, G and Vilbrun, SC and Walsh, KF and Fitzgerald, DW and Glickman, MS and Bucci, V}, title = {Commensal antimicrobial resistance mediates microbiome resilience to antibiotic disruption.}, journal = {Science translational medicine}, volume = {16}, number = {730}, pages = {eadi9711}, pmid = {38232140}, issn = {1946-6242}, support = {R01 GM129325/GM/NIGMS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; K23 AI175686/AI/NIAID NIH HHS/United States ; R01 AG075283/AG/NIA NIH HHS/United States ; U01 AI172987/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U19 AI162568/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; Anti-Bacterial Agents/pharmacology/therapeutic use ; *Resilience, Psychological ; Drug Resistance, Bacterial/genetics ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {Despite their therapeutic benefits, antibiotics exert collateral damage on the microbiome and promote antimicrobial resistance. However, the mechanisms governing microbiome recovery from antibiotics are poorly understood. Treatment of Mycobacterium tuberculosis, the world's most common infection, represents the longest antimicrobial exposure in humans. Here, we investigate gut microbiome dynamics over 20 months of multidrug-resistant tuberculosis (TB) and 6 months of drug-sensitive TB treatment in humans. We find that gut microbiome dynamics and TB clearance are shared predictive cofactors of the resolution of TB-driven inflammation. The initial severe taxonomic and functional microbiome disruption, pathobiont domination, and enhancement of antibiotic resistance that initially accompanied long-term antibiotics were countered by later recovery of commensals. This resilience was driven by the competing evolution of antimicrobial resistance mutations in pathobionts and commensals, with commensal strains with resistance mutations reestablishing dominance. Fecal-microbiota transplantation of the antibiotic-resistant commensal microbiome in mice recapitulated resistance to further antibiotic disruption. These findings demonstrate that antimicrobial resistance mutations in commensals can have paradoxically beneficial effects by promoting microbiome resilience to antimicrobials and identify microbiome dynamics as a predictor of disease resolution in antibiotic therapy of a chronic infection.}, }
@article {pmid38231673, year = {2024}, author = {Sung, C and Park, CG and Maienschein-Cline, M and Chlipala, G and Green, S and Doorenbos, A and Fink, A and Bronas, U and Lockwood, M}, title = {Associations Between Gut Microbial Features and Sickness Symptoms in Kidney Transplant Recipients.}, journal = {Biological research for nursing}, volume = {26}, number = {3}, pages = {368-379}, doi = {10.1177/10998004241227560}, pmid = {38231673}, issn = {1552-4175}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; Female ; Prospective Studies ; Middle Aged ; Longitudinal Studies ; Adult ; Cross-Sectional Studies ; Transplant Recipients/statistics &amp; numerical data ; Feces/microbiology ; }, abstract = {PURPOSE: The study investigated the relationship of gut microbiome features and sickness symptoms in kidney transplant recipients.<br><br>METHODS: Employing a prospective, longitudinal design, we collected data from 19 participants who had undergone living-donor kidney transplant at three timepoints (pre-transplant and 1&#xa0;week and 3&#xa0;months post-transplant). Sickness symptom data and fecal specimens were collected at each timepoint. Participants were grouped either as high or low sickness symptom severity at baseline. Shotgun metagenomics sequencing characterized gut microbial structure and functional gene content. Fecal microbial features, including alpha (evenness and richness within samples) and beta (dissimilarities between samples) diversity and relative abundances, were analyzed using R statistical packages. Cross-sectional and longitudinal analyses examined relationships between gut microbial features and sickness symptoms.<br><br>RESULTS: Although our exploratory findings revealed no significant differences in alpha and beta diversity between groups, the high-severity group showed lower microbial richness and evenness than the low-severity group. The high-severity group had enriched relative abundance of bacteria from the genera Citrobacter and Enterobacter and reduced relative abundance of bacteria from the genus Akkermansia across timepoints. No functional genes differed significantly between groups or timepoints.<br><br>CONCLUSIONS: Kidney transplant recipients with high symptom burden displayed increased putative proinflammatory bacteria and decreased beneficial bacteria. This study provides an effect size that future large cohort studies can employ to confirm associations between gut microbial features and sickness symptom experiences in the kidney transplant population. The study findings also have implications for future interventional studies aiming to alleviate the sickness symptom burden in this population.}, }
@article {pmid38228976, year = {2024}, author = {Babu, A and Devi Rajeswari, V and Ganesh, V and Das, S and Dhanasekaran, S and Usha Rani, G and Ramanathan, G}, title = {Gut Microbiome and Polycystic Ovary Syndrome: Interplay of Associated Microbial-Metabolite Pathways and Therapeutic Strategies.}, journal = {Reproductive sciences (Thousand Oaks, Calif.)}, volume = {31}, number = {6}, pages = {1508-1520}, pmid = {38228976}, issn = {1933-7205}, mesh = {*Polycystic Ovary Syndrome/metabolism/microbiology/therapy ; Humans ; Female ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy ; *Probiotics/therapeutic use/administration &amp; dosage ; Prebiotics/administration &amp; dosage ; Brain-Gut Axis/physiology ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Polycystic ovary syndrome (PCOS) is a multifaceted disease with an intricate etiology affecting reproductive-aged women. Despite attempts to unravel the pathophysiology, the molecular mechanism of PCOS remains unknown. There are no effective or suitable therapeutic strategies available to ameliorate PCOS; however, the symptoms can be managed. In recent years, a strong association has been found between the gut microbiome and PCOS, leading to the formulation of novel ideas on the genesis and pathological processes of PCOS. Further, gut microbiome dysbiosis involving microbial metabolites may trigger PCOS symptoms via many mechanistic pathways including those associated with carbohydrates, short-chain fatty acids, lipopolysaccharides, bile acids, and gut-brain axis. We present the mechanistic pathways of PCOS-related microbial metabolites and therapeutic opportunities available to treat PCOS, such as prebiotics, probiotics, and fecal microbiota therapy. In addition, the current review highlights the emerging treatment strategies available to alleviate the symptoms of PCOS.}, }
@article {pmid38227935, year = {2024}, author = {Renga, G and Nunzi, E and Stincardini, C and Pariano, M and Puccetti, M and Pieraccini, G and Di Serio, C and Fraziano, M and Poerio, N and Oikonomou, V and Mosci, P and Garaci, E and Fianchi, L and Pagano, L and Romani, L}, title = {CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance, and immune homeostasis.}, journal = {Blood}, volume = {143}, number = {16}, pages = {1628-1645}, doi = {10.1182/blood.2023021380}, pmid = {38227935}, issn = {1528-0020}, mesh = {Adult ; Humans ; *Gastrointestinal Microbiome ; Antifungal Agents/therapeutic use ; Dysbiosis/etiology ; Daunorubicin ; *Leukemia, Myeloid, Acute/drug therapy ; Cytarabine ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Homeostasis ; }, abstract = {CPX-351, a liposomal combination of cytarabine plus daunorubicin, has been approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes, because it improves survival and outcome of patients who received hematopoietic stem cell transplant compared with the continuous infusion of cytarabine plus daunorubicin (referred to as "7 + 3" combination). Because gut dysbiosis occurring in patients with AML during induction chemotherapy heavily affects the subsequent phases of therapy, we have assessed whether the superior activity of CPX-351 vs "7 + 3" combination in the real-life setting implicates an action on and by the intestinal microbiota. To this purpose, we have evaluated the impact of CPX-351 and "7 + 3" combination on mucosal barrier function, gut microbial composition and function, and antifungal colonization resistance in preclinical models of intestinal damage in vitro and in vivo and fecal microbiota transplantation. We found that CPX-351, at variance with "7 + 3" combination, protected from gut dysbiosis, mucosal damage, and gut morbidity while increasing antifungal resistance. Mechanistically, the protective effect of CPX-351 occurred through pathways involving both the host and the intestinal microbiota, namely via the activation of the aryl hydrocarbon receptor-interleukin-22 (IL-22)-IL-10 host pathway and the production of immunomodulatory metabolites by anaerobes. This study reveals how the gut microbiota may contribute to the good safety profile, with a low infection-related mortality, of CPX-351 and highlights how a better understanding of the host-microbiota dialogue may contribute to pave the way for precision medicine in AML.}, }
@article {pmid38227850, year = {2024}, author = {Marasco, G and Cremon, C and Barbaro, MR and Stanghellini, V and Barbara, G}, title = {Journal of Clinical Gastroenterology Lectureship Dubai 2022 : Management of Irritable Bowel Syndrome With Diarrhea.}, journal = {Journal of clinical gastroenterology}, volume = {58}, number = {3}, pages = {221-231}, pmid = {38227850}, issn = {1539-2031}, mesh = {Humans ; *Irritable Bowel Syndrome/complications/therapy ; Quality of Life ; *Gastroenterology ; Gastrointestinal Agents/therapeutic use ; Diarrhea/therapy/chemically induced ; Abdominal Pain/etiology/therapy ; }, abstract = {Irritable bowel syndrome (IBS) with diarrhea (IBS-D) affects ~1% of the general population and is characterized by abdominal pain associated with diarrhea. IBS-D symptoms significantly impact the quality of life of patients. Major uncertainties remain regarding the optimal management of these patients. Several therapies have been investigated over the years for the treatment of IBS-D. In the initial management, commonly prescribed approaches with an effect on global IBS symptoms include a low Fermentable Oligo-, Di-, Mono-Saccharides and Polyols diet and probiotics, while antispasmodics are used for targeting abdominal pain and loperamide for diarrhea only. Additional therapeutic options for the relief of global IBS symptoms include rifaximin, 5-HT 3 antagonists, gut-directed psychological therapies, and eluxadoline, while tricyclic antidepressants can target abdominal pain and bile acid sequestrants diarrhea. Promising evidence exists for the use of mesalazine and fecal microbiota transplantation in IBS-D, although further evidence is needed for definitive conclusions regarding their efficacy.}, }
@article {pmid38227539, year = {2024}, author = {Fang, X and Liu, S and Muhammad, B and Zheng, M and Ge, X and Xu, Y and Kan, S and Zhang, Y and Yu, Y and Zheng, K and Geng, D and Liu, CF}, title = {Gut microbiota dysbiosis contributes to α-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson's disease.}, journal = {Neural regeneration research}, volume = {19}, number = {9}, pages = {2081-2088}, pmid = {38227539}, issn = {1673-5374}, abstract = {JOURNAL/nrgr/04.03/01300535-202409000-00042/figure1/v/2024-01-16T170235Z/r/image-tiff Parkinson's disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction. Gastrointestinal dysfunction can precede the onset of motor symptoms by several years. Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson's disease, whether it plays a causal role in motor dysfunction, and the mechanism underlying this potential effect, remain unknown. CCAAT/enhancer binding protein β/asparagine endopeptidase (C/EBPβ/AEP) signaling, activated by bacterial endotoxin, can promote α-synuclein transcription, thereby contributing to Parkinson's disease pathology. In this study, we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling, α-synuclein-related pathology, and motor symptoms using a rotenone-induced mouse model of Parkinson's disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation. We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier, as well as activation of the C/EBP/AEP pathway, α-synuclein aggregation, and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits. However, treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics. Importantly, we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits, intestinal inflammation, and endotoxemia. Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits, intestinal inflammation, endotoxemia, and intestinal barrier impairment. These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits, C/EBPβ/AEP signaling activation, and α-synuclein-related pathology in a rotenone-induced mouse model of Parkinson's disease. Additionally, our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson's disease.}, }
@article {pmid38226811, year = {2024}, author = {Zhang, Q and Guan, G and Liu, J and Hu, W and Jin, P}, title = {Gut microbiota dysbiosis and decreased levels of acetic and propionic acid participate in glucocorticoid-induced glycolipid metabolism disorder.}, journal = {mBio}, volume = {15}, number = {2}, pages = {e0294323}, pmid = {38226811}, issn = {2150-7511}, support = {81670730//MOST | National Natural Science Foundation of China (NSFC)/ ; 2021JJ31007//National Natural Science Foundation of China Hunan Province/ ; 202103061081//Research Project of Hunan Health Committee/ ; }, mesh = {Humans ; Animals ; Mice ; Propionates ; Glucocorticoids/adverse effects ; *Gastrointestinal Microbiome ; *Cushing Syndrome ; Dysbiosis/chemically induced ; *Metabolic Diseases ; Proteobacteria ; Acetic Acid ; Clostridiales ; Disease Models, Animal ; Faecalibacterium ; Glucagon-Like Peptide 1 ; Glycolipids ; RNA, Messenger ; }, abstract = {Long-term/high-dose glucocorticoid (GC) use results in glycolipid metabolism disorder, which severely limits its clinical application. The role of the gut microbiota and its metabolites in GC-induced glycolipid metabolism disorder remains unclear. Our previous human study found that obvious gut microbiota dysbiosis characterized by an increasing abundance of Proteobacteria and a decreased abundance of Lachnospiraceae and Faecalibacterium were observed in patients with endogenous hypercortisolism. In this study, we established a mouse model of GC-induced glycolipid metabolism disorder (Dex group) and found that the relative abundances of Proteobacteria and Parasuttrerella were increased, while the abundances of Lachnospiraceae, Faecalibacterium, and Lachnospiraceae_NK4A136_group were decreased significantly in the Dex group. Compared with the control group, serum total short-chain fatty acids (SCFAs), acetic acid, propionic acid, and GLP-1 levels were all decreased in the Dex group. The mRNA expression of the GPR41 receptor and Pcsk1 in the colon was significantly decreased in the Dex group. Furthermore, GC-induced glycolipid metabolism disorder could be alleviated by depletion of the gut microbiota or fecal bacteria transplantation with control bacteria. The abundances of Lachnospiraceae_NK4A136_group and the serum GLP-1 levels were significantly increased, while the abundances of Proteobacteria and Parasutterella were significantly decreased after fecal bacteria transplantation with control bacteria. Our work indicates that gut microbiota dysbiosis and decreased levels of serum acetic acid and propionic acid may participate in GC-induced glycolipid metabolism disorder. These findings may provide novel insights into the prevention and treatment of GC-induced metabolic disorders.IMPORTANCEThe role of the gut microbiota in glucocorticoid (GC)-induced glycolipid metabolism disorder remains unclear. In our study, gut microbiota dysbiosis characterized by an increased abundance of Proteobacteria/Parasuttrerella and a decreased abundance of Lachnospiraceae_NK4A136_group was observed in mice with GC-induced glycolipid metabolism disorder. Some bacteria were shared in our previous study in patients with endogenous hypercortisolism and the mouse model used in the study. Furthermore, the depletion of the gut microbiota and fecal bacteria transplantation with control bacteria could alleviate GC-induced glycolipid metabolism disorder. Plasma acetic acid, propionic acid, and GLP-1 and the mRNA expression of the GPR41 receptor and Pcsk1 in the colon were decreased significantly in mice with GC-induced glycolipid metabolism disorder, which indicated that the gut microbiota/SCFA/GPR41/GLP-1 axis may participate in GC-induced glycolipid metabolism disorder. Our findings indicate that the gut microbiota may serve as a novel therapeutic target for GC-related metabolic disorders.}, }
@article {pmid38224464, year = {2024}, author = {Bu, L and Wang, C and Bai, J and Song, J and Zhang, Y and Chen, H and Suo, H}, title = {Gut microbiome-based therapies for alleviating cognitive impairment: state of the field, limitations, and future perspectives.}, journal = {Food &amp; function}, volume = {15}, number = {3}, pages = {1116-1134}, doi = {10.1039/d3fo02307a}, pmid = {38224464}, issn = {2042-650X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics ; Diet ; *Cognitive Dysfunction/therapy ; }, abstract = {Cognitive impairment (CI) is a multifaceted neurological condition that can trigger negative emotions and a range of concurrent symptoms, imposing significant public health and economic burdens on society. Therefore, it is imperative to discover a remedy for CI. Nevertheless, the mechanisms behind the onset of this disease are multifactorial, which makes the search for effective amelioration difficult and complex, hindering the search for effective measures. Intriguingly, preclinical research indicates that gut microbiota by influencing brain function, plays an important role in the progression of CI. Furthermore, numerous preclinical studies have highlighted the potential of probiotics, prebiotics, fecal microbiota transplantation (FMT), and diet in modulating the gut microbiota, thereby ameliorating CI symptoms. This review provides a comprehensive evaluation of CI pathogenesis, emphasizing the contribution of gut microbiota disorders to CI development. It also summarizes and discusses current strategies and mechanisms centered on the synergistic role of gut microbiota modulation in the microbiota-gut-brain axis in CI development. Finally, problems with existing approaches are contemplated and the development of microbial modulation strategies as therapeutic approaches to promote and restore brain cognition is discussed. Further research considerations and directions are highlighted to provide ideas for future CI prevention and treatment strategies.}, }
@article {pmid38223927, year = {2024}, author = {Wu, H and Zhang, P and Zhou, J and Hu, S and Hao, J and Zhong, Z and Yu, H and Yang, J and Chi, J and Guo, H}, title = {Paeoniflorin confers ferroptosis resistance by regulating the gut microbiota and its metabolites in diabetic cardiomyopathy.}, journal = {American journal of physiology. Cell physiology}, volume = {326}, number = {3}, pages = {C724-C741}, doi = {10.1152/ajpcell.00565.2023}, pmid = {38223927}, issn = {1522-1563}, support = {82174204//MOST | National Natural Science Foundation of China (NSFC)/ ; 81873120//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Animals ; Mice ; *Diabetic Cardiomyopathies/drug therapy ; *Gastrointestinal Microbiome ; *Ferroptosis ; Myocardium ; *Diabetes Mellitus ; *Glucosides ; *Monoterpenes ; }, abstract = {Diabetic cardiomyopathy (DCM) is closely related to ferroptosis, a new type of cell death that mainly manifests as intracellular iron accumulation and lipid peroxidation. Paeoniflorin (PA) helps to improve impaired glucose tolerance, influences the distribution of the intestinal flora, and induces significant resistance to ferroptosis in several models. In this study, we found that PA improved cardiac dysfunction in mice with DCM by alleviating myocardial damage, resisting oxidative stress and ferroptosis, and changing the community composition and structure of the intestinal microbiota. Metabolomics analysis revealed that PA-treated fecal microbiota transplantation affected metabolites in DCM mice. Based on in vivo and in vitro experiments, 11,12-epoxyeicosatrienoic acid (11,12-EET) may serve as a key contributor that mediates the cardioprotective and antiferroptotic effects of PA-treated fecal microbiota transplantation (FMT) in DCM mice.NEW &amp; NOTEWORTHY This study demonstrated for the first time that paeoniflorin (PA) exerts protective effects in diabetic cardiomyopathy mice by alleviating myocardial damage, resisting ferroptosis, and changing the community composition and structure of the intestinal microbiota, and 11,12-epoxyeicosatrienoic acid (11,12-EET) may serve as a key contributor in its therapeutic efficacy.}, }
@article {pmid38223735, year = {2024}, author = {Zhou, Y and Liu, X and Gao, W and Luo, X and Lv, J and Wang, Y and Liu, D}, title = {The role of intestinal flora on tumor immunotherapy: recent progress and treatment implications.}, journal = {Heliyon}, volume = {10}, number = {1}, pages = {e23919}, pmid = {38223735}, issn = {2405-8440}, abstract = {Immunotherapy, specifically immune checkpoint inhibitors, has emerged as a promising approach for treating malignant tumors. The gut, housing approximately 70 % of the body's immune cells, is abundantly populated with gut bacteria that actively interact with the host's immune system. Different bacterial species within the intestinal flora are in a delicate equilibrium and mutually regulate each other. However, when this balance is disrupted, pathogenic microorganisms can dominate, adversely affecting the host's metabolism and immunity, ultimately promoting the development of disease. Emerging researches highlight the potential of interventions such as fecal microflora transplantation (FMT) to improve antitumor immune response and reduce the toxicity of immunotherapy. These remarkable findings suggest the major role of intestinal flora in the development of cancer immunotherapy and led us to the hypothesis that intestinal flora transplantation may be a new breakthrough in modifying immunotherapy side effects.}, }
@article {pmid38223452, year = {2023}, author = {Qu, C and Xu, QQ and Yang, W and Zhong, M and Yuan, Q and Xian, YF and Lin, ZX}, title = {Gut dysbiosis aggravates cognitive deficits, amyloid pathology and lipid metabolism dysregulation in a transgenic mouse model of Alzheimer's disease.}, journal = {Journal of pharmaceutical analysis}, volume = {13}, number = {12}, pages = {1526-1547}, pmid = {38223452}, issn = {2214-0883}, abstract = {Gut dysbiosis, a well-known risk factor to triggers the progression of Alzheimer's disease (AD), is strongly associated with metabolic disturbance. Trimethylamine N-oxide (TMAO), produced in the dietary choline metabolism, has been found to accelerate neurodegeneration in AD pathology. In this study, the cognitive function and gut microbiota of TgCRND8 (Tg) mice of different ages were evaluated by Morris water maze task (MWMT) and 16S rRNA sequencing, respectively. Young pseudo germ-free (PGF) Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type (WT) mice were selected to determine the role of the gut microbiota in the process of neuropathology. Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions. Our results showed that gut dysbiosis, neuroinflammation response, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and cyclin-dependent kinase 5 (CDK5)/transcription 3 (STAT3) activation occurred in Tg mice age-dependently. Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice, with the activation of CDK5/STAT3 signaling in the brains. On the contrary, faecal microbiota transplantation from WT mice alleviated the cognitive deficits, attenuated neuroinflammation, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice. Moreover, excessive choline treatment was also shown to aggravate the cognitive deficits, Aβ deposition, neuroinflammation and CDK5/STAT3 pathway activation. These findings provide a novel insight into the interaction between gut dysbiosis and AD progression, clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.}, }
@article {pmid38216845, year = {2024}, author = {Cintron, M and Jani, K and Madhavappallil, J and Kamboj, M and Babady, NE}, title = {Prevalence of astrovirus and sapovirus among adult oncology patients with acute gastroenteritis using a multiplexed gastrointestinal pathogen PCR panel.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {43}, number = {3}, pages = {525-531}, pmid = {38216845}, issn = {1435-4373}, mesh = {Adult ; Humans ; Infant ; *Sapovirus/genetics ; Prevalence ; Retrospective Studies ; *Norovirus/genetics ; *Gastroenteritis/diagnosis ; Diarrhea/epidemiology ; *Neoplasms/complications ; Feces ; Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Multiplex syndromic gastrointestinal panels (GIPCR) have streamlined the diagnosis of infectious diarrhea. Additionally, they have expanded the number of pathogens that can be routinely evaluated, allowing further understanding of the prevalence of enteric pathogens in various patient populations. The goal of this study was to investigate the prevalence and clinical presentation of astrovirus and sapovirus gastroenteritis in adult oncology patients as detected by the FilmArray GIPCR.<br><br>METHODS: All GIPCR panel results from December 2017 to June 2021 were retrospectively reviewed to determine the prevalence of astrovirus and sapovirus in adult oncology patients. Medical records were also reviewed to obtain clinical information. Repeat GIPCR positivity and symptom duration were used to estimate prolonged viral shedding.<br><br>RESULTS: A total of 18,014 panels were performed on samples collected from 9303 adults. Overall, astrovirus and sapovirus were detected in 0.35% (33/9303) and 0.45% (42/9303) GIPCRs respectively. At least one viral target was detected in 424 (4.4%) patients. Astrovirus accounted for 7.8% (33/424) and sapovirus 9.9% (42/424) of patients. Diarrhea was the most common symptom documented. A subset of transplant patients had protracted viral detection with a median of ~27 days (range 23-43 days) for astrovirus and 97 days (range 11-495) for sapovirus. No clusters or outbreaks were identified during the study period.<br><br>CONCLUSION: In oncology patients with viral gastroenteritis, astrovirus and sapovirus were the causative agents in 18% of the cases. Both viruses were associated with mild disease. Prolonged diarrhea and viral shedding were observed in a few transplant patients.}, }
@article {pmid38216353, year = {2024}, author = {Powell-Brett, S and Halle-Smith, JM and Hall, LA and Hodson, J and Phillips, ME and Roberts, KJ}, title = {Comprehensive, long-term evaluation of pancreatic exocrine insufficiency after pancreatoduodenectomy.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {24}, number = {2}, pages = {298-305}, doi = {10.1016/j.pan.2023.11.016}, pmid = {38216353}, issn = {1424-3911}, mesh = {Humans ; Pancreaticoduodenectomy/adverse effects ; Quality of Life ; *Body Fluids ; Breath Tests ; *Exocrine Pancreatic Insufficiency/diagnosis/epidemiology/etiology ; }, abstract = {AIMS: Treatment of pancreatic exocrine insufficiency (PEI) following pancreatoduodenectomy (PD) improves quality of life, clinical outcomes, and survival. However, diagnosing PEI following PD is challenging owing to the difficulties with current tests and often non-specific symptoms. This work aims to quantify the true rate of long-term PEI in patients following a PD.<br><br>METHODS: Patients underwent a PEI screen approximately one to two years following PD for oncologic indication, including the [13]C Mixed triglyceride breath test ([13]CMTGT), faecal elastase 1 (FE-1) and the PEI Questionnaire (PEI-Q). Four reviewers with expertise in PEI reviewed the results blinded to other decisions to classify PEI status; disagreements were resolved on consensus.<br><br>RESULTS: 26 patients were recruited. Of those with valid test results, these were indicative of PEI based on pre-specified thresholds for 60&#xa0;% (15/25) for the [13]CMTGT, 82&#xa0;% (18/22) for FE-1, and 88&#xa0;% (22/25) for the PEI-Q. After discussion between reviewers, the consensus PEI prevalence was 81&#xa0;% (95&#xa0;% CI: 61-93&#xa0;%; 21/26), with 50&#xa0;% (N&#xa0;=&#xa0;13) classified as having severe, 23&#xa0;% (N&#xa0;=&#xa0;6) moderate, and 8&#xa0;% (N&#xa0;=&#xa0;2) mild PEI.<br><br>DISCUSSION: Since no ideal test exists for PEI, this collation of diagnostic modalities and blinded expert review was designed to ascertain the true rate of long-term PEI following PD. This required our cohort to survive a year, travel to hospital, and undergo a period of starvation and PERT hold, and therefore there is likely to be recruitment bias towards fitter, younger patients with less aggressive pathology. Despite this, over 80&#xa0;% were deemed to have PEI, with over 90&#xa0;% of these being considered moderate or severe.}, }
@article {pmid38214604, year = {2024}, author = {Hartikainen, AK and Khan, I and Karjalainen, EK and Renkonen-Sinisalo, L and Arkkila, P and Jalanka, J and Lepistö, AH and Satokari, R}, title = {Microbiota and mucosal gene expression of fecal microbiota transplantation or placebo treated patients with chronic pouchitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2295445}, pmid = {38214604}, issn = {1949-0984}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Pouchitis/therapy/metabolism ; *Colitis, Ulcerative/therapy ; *Gastrointestinal Microbiome ; *Microbiota ; Gene Expression ; Feces ; }, abstract = {Altered microbiota and impaired host immune function have been linked to the pathogenesis of pouchitis. We used 16S rRNA gene sequencing and RNA sequencing data from a previous randomized clinical trial (RCT) on fecal microbiota transplantation (FMT) therapy in 26 chronic pouchitis patients with one-year follow-up. We analyzed changes in both luminal and mucosal microbiota composition, as well as in host mucosal gene expression to gain insights into the host-microbiota interactions possibly underlying clinical outcomes of the patients. Antibiotic type and pattern of use were significant drivers of the luminal microbiota at baseline. Differential gene expression analysis indicated transition from ileal to colonic gene expression in the pouch, and upregulation in inflammation- and immune system-related pathways in the pouch. At 4 weeks, the non-relapsed FMT patients had a lower microbiota dissimilarity to the donor than the non-relapsed placebo patients (p = .02). While two FMT-treated patients showed a shift toward the donor's microbiota during the one-year follow-up, the overall FMT microbiota modulation effect was low. Patient's luminal and mucosal microbiota profiles were unstable in both FMT and placebo groups. Expression of the chemokine receptor CXCR4 was downregulated at 52 weeks compared to the baseline in the non-relapsed patients in both FMT and placebo groups. Microbiota modulation by FMT seems to be low in this patient group. The microbiota composition or alterations did not explain the relapse status of the patients. Some evidence for remission-related host gene expression pattern was found; specifically, CXCR4 expression may have a role in sustained remission.}, }
@article {pmid38213259, year = {2024}, author = {Yunqi, X and Junxiang, LI and Yali, Y and Tangyou, M}, title = {The combination of gut microbiota-depleted treatment and fecal microbiota transplantation is an important strategy to verify the efficacy of Traditional Chinese Medicine though modulation of gut dysbiosis.}, journal = {Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan}, volume = {44}, number = {1}, pages = {222-223}, pmid = {38213259}, issn = {2589-451X}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Medicine, Chinese Traditional ; Dysbiosis/therapy ; Feces ; }, }
@article {pmid38212672, year = {2024}, author = {Youngster, I and Eshel, A and Geva, M and Danylesko, I and Henig, I and Zuckerman, T and Fried, S and Yerushalmi, R and Shem-Tov, N and Fein, JA and Bomze, D and Shimoni, A and Koren, O and Shouval, R and Nagler, A}, title = {Fecal microbiota transplantation in capsules for the treatment of steroid refractory and steroid dependent acute graft vs. host disease: a pilot study.}, journal = {Bone marrow transplantation}, volume = {59}, number = {3}, pages = {409-416}, pmid = {38212672}, issn = {1476-5365}, support = {K08CA282987//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; }, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; Pilot Projects ; Prospective Studies ; Gastrointestinal Tract ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Graft vs Host Disease/etiology ; Steroids ; }, abstract = {Acute graft-versus-host disease (aGvHD) is a serious complication of allogeneic hematopoietic stem-cell transplantation with limited treatment options. The gut microbiome plays a critical role in aGvHD pathogenesis. Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach to restore gut microbial diversity. In this prospective pilot study, 21 patients with steroid-resistant or steroid-dependent lower gastrointestinal aGvHD received FMT in capsule form. At 28 days after the first FMT, the overall response rate was 52.4%, with 23.8% complete and 28.6% partial responses. However, sustained responses were infrequent, with only one patient remaining aGvHD-free long-term. FMT was generally well-tolerated. Microbiome analysis revealed dysbiosis in pre-FMT patient stool samples, with distinct microbial characteristics compared to donors. Following FMT, there was an increase in beneficial Clostridiales and a decrease in pathogenic Enterobacteriales. These findings highlight the potential of FMT as a treatment option for steroid-resistant aGvHD. Trial registration number NCT #03214289.}, }
@article {pmid38203833, year = {2024}, author = {Ahn, JS and Koo, BC and Choi, YJ and Jung, WW and Kim, HS and Lee, SJ and Hong, ST and Chung, HJ}, title = {Identification of Muscle Strength-Related Gut Microbes through Human Fecal Microbiome Transplantation.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203833}, issn = {1422-0067}, support = {C380300//Korea Basic Science Institute/ ; C320000//Korea Basic Science Institute/ ; C330340//Korea Basic Science Institute/ ; HV22C0171//Korea Health Industry Development Institute/Republic of Korea ; RS-2023-00224099//National Research Foundation of Korea/ ; }, mesh = {Humans ; Animals ; Mice ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Microbiota ; Feces ; Muscle Strength ; }, abstract = {The gut microbiome is well known for its influence on human physiology and aging. Therefore, we speculate that the gut microbiome may affect muscle strength in the same way as the host's own genes. To demonstrate candidates for gut microbes affecting muscle strength, we remodeled the original gut microbiome of mice into human intestinal microbiome through fecal microbiome transplantation (FMT), using human feces and compared the changes in muscle strength in the same mice before and three months after FMT. After comparing before and after FMT, the mice were divided into three groups based on the observed changes in muscle strength: positive, none, and negative changes in muscle strength. As a result of analyzing the α-diversity, β-diversity, and co-occurrence network of the intestinal microbial community before and after FMT, it was observed that a more diverse intestinal microbial community was established after FMT in all groups. In particular, the group with increased muscle strength had more gut microbiome species and communities than the other groups. Fold-change comparison showed that Eisenbergiella massiliensis and Anaeroplasma abactoclasticum from the gut microbiome had positive contributions to muscle strength, while Ileibacterium valens and Ethanoligenens harbinense had negative effects. This study identifies candidates for the gut microbiome that contribute positively and those that contribute negatively to muscle strength.}, }
@article {pmid38203771, year = {2024}, author = {Feješ, A and Belvončíková, P and Porcel Sanchis, D and Borbélyová, V and Celec, P and Džunková, M and Gardlík, R}, title = {The Effect of Cross-Sex Fecal Microbiota Transplantation on Metabolism and Hormonal Status in Adult Rats.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203771}, issn = {1422-0067}, support = {APVV-21-0370//Slovak Research and Development Agency/ ; VEGA 1/0649/21//Ministry of Education, Science, Research and Sport of the Slovak Republic/ ; VEGA 1/0398/24//Ministry of Education, Science, Research and Sport of the Slovak Republic/ ; CDEIGENT/2021/008//Generalitat Valenciana/ ; CIACIF/2022/070//Generalitat Valenciana/ ; }, mesh = {Animals ; Female ; Male ; Rats ; *Fecal Microbiota Transplantation ; Lipid Metabolism ; Rats, Wistar ; Testosterone/blood ; }, abstract = {Increasing evidence of sexual dimorphism in the pathophysiology of metabolic complications caused by sex steroids is under investigation. The gut microbiota represents a complex microbial ecosystem involved in energy metabolism, immune response, nutrition acquisition, and the health of host organisms. Gender-specific differences in composition are present between females and males. The purpose of this study was to use cross-sex fecal microbiota transplantation (FMT) for the detection of sex-dependent metabolic, hormonal, and gut microbiota changes in female and male recipients. Healthy non-obese female and male Wistar rats were divided into donor, same-sex, and cross-sex recipient groups. After a 30-day period of FMT administration, biochemical markers (glucose and lipid metabolism) and sex hormones were measured, and the gut microbiota was analyzed. The cross-sex male recipients displayed a significantly lower testosterone concentration compared to the males that received same-sex FMT. Sex-dependent changes caused by cross-sex FMT were detected, while several bacterial taxa correlated with plasma testosterone levels. This study represents the first to study the effect of cross-sex changes in the gut microbiome concerning metabolic and hormonal changes/status in adult non-obese Wistar rats. Herein, we present cross-sex FMT as a potential tool to modify sex-specific pathologies.}, }
@article {pmid38202028, year = {2023}, author = {Friis, KH and Thomsen, KL and Laleman, W and Montagnese, S and Vilstrup, H and Lauridsen, MM}, title = {Post-Transjugular Intrahepatic Portosystemic Shunt (TIPS) Hepatic Encephalopathy-A Review of the Past Decade's Literature Focusing on Incidence, Risk Factors, and Prophylaxis.}, journal = {Journal of clinical medicine}, volume = {13}, number = {1}, pages = {}, pmid = {38202028}, issn = {2077-0383}, abstract = {Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for portal hypertension and its' complications in liver cirrhosis, yet the development of hepatic encephalopathy (HE) remains a significant concern. This review covers the reported incidence, risk factors, and management strategies for post-TIPS HE over the past decade. Incidence varies widely (7-61%), with factors like age, liver function, hyponatremia, and spontaneous portosystemic shunts influencing risk. Procedural aspects, including TIPS timing, indication, and stent characteristics, also contribute. Pharmacological prophylaxis with lactulose and rifaximin shows promise, but current evidence is inconclusive. Procedural preventive measures, such as shunt embolization and monitoring portal pressure gradients, are explored. Treatment involves pharmacological options like lactulose and rifaximin, and procedural interventions like stent diameter reduction. Ongoing studies on novel predictive markers and emerging treatments, such as faecal microbiota transplant, reflect the evolving landscape in post-TIPS HE management. This concise review provides clinicians with insights into the multifaceted nature of post-TIPS HE, aiding in improved risk assessment, prophylaxis, and management for patients undergoing TIPS procedures.}, }
@article {pmid38201921, year = {2023}, author = {Poto, R and Fusco, W and Rinninella, E and Cintoni, M and Kaitsas, F and Raoul, P and Caruso, C and Mele, MC and Varricchi, G and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {The Role of Gut Microbiota and Leaky Gut in the Pathogenesis of Food Allergy.}, journal = {Nutrients}, volume = {16}, number = {1}, pages = {}, pmid = {38201921}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Food Hypersensitivity/prevention &amp; control ; Fecal Microbiota Transplantation ; Health Status ; Intestinal Barrier Function ; }, abstract = {Food allergy (FA) is a growing public health concern, with an increasing prevalence in Western countries. Increasing evidence suggests that the balance of human gut microbiota and the integrity of our intestinal barrier may play roles in the development of FA. Environmental factors, including industrialization and consumption of highly processed food, can contribute to altering the gut microbiota and the intestinal barrier, increasing the susceptibility to allergic sensitization. Compositional and functional alterations to the gut microbiome have also been associated with FA. In addition, increased permeability of the gut barrier allows the translocation of allergenic molecules, triggering Th2 immune responses. Preclinical and clinical studies have highlighted the potential of probiotics, prebiotics, and postbiotics in the prevention and treatment of FA through enhancing gut barrier function and promoting the restoration of healthy gut microbiota. Finally, fecal microbiota transplantation (FMT) is now being explored as a promising therapeutic strategy to prevent FA in both experimental and clinical studies. In this review article, we aim to explore the complex interplay between intestinal permeability and gut microbiota in the development of FA, as well as depict potential therapeutic strategies.}, }
@article {pmid38197171, year = {2024}, author = {Huang, Y and Ge, R and Qian, J and Lu, J and Qiao, D and Chen, R and Jiang, H and Cui, D and Zhang, T and Wang, N and He, S and Wang, M and Yan, F}, title = {Lacticaseibacillus rhamnosus GG Improves Periodontal Bone Repair via Gut-Blood Axis in Hyperlipidemia.}, journal = {Journal of dental research}, volume = {103}, number = {3}, pages = {253-262}, doi = {10.1177/00220345231217402}, pmid = {38197171}, issn = {1544-0591}, mesh = {Rats ; Animals ; *Lacticaseibacillus rhamnosus ; *Hyperlipidemias/complications ; Selenomethionine ; Rats, Sprague-Dawley ; *Alveolar Bone Loss ; *Periodontitis/therapy ; *Probiotics/therapeutic use ; }, abstract = {Periodontal bone regeneration remains a clinical challenge, and hyperlipidemia can aggravate alveolar bone resorption. Probiotics have recently been reported to improve bone mass. We aimed to determine the role of Lacticaseibacillus rhamnosus GG (LGG) in periodontal bone regeneration improvement within the context of periodontitis with hyperlipidemia. A Sprague Dawley rat model for periodontitis, hyperlipidemia, and periodontal fenestration defect was constructed (n = 36) and administered LGG gavage for 6 wk (the rats were subsequently sacrificed). Fecal microbiota from donor rats 3 wk after LGG gavage was transplanted into recipient rats to evaluate the role of LGG-modulated gut microbiota in periodontal bone regeneration. Regenerated bone mass was detected using micro-computerized tomography and hematoxylin and eosin stain. Gut microbiota was analyzed using 16S ribosomal RNA sequencing. Serum metabolites were detected by liquid chromatography-mass spectrometry (6 wk after LGG gavage). The pro-osteogenic effects of screened serum metabolite were verified in vitro on bone marrow mesenchymal stem cells (BMMSCs). We found that the bone mineral density, bone volume (BV), trabecular bone volume fraction (BV/TV), and trabecular thickness of the regenerated periodontal bone increased after LGG gavage (P < 0.05) but had little effect on oral flora. After LGG gavage, Staphylococcus, Corynebacterium, and Collinsella in the gut of donors were significantly changed, and these differences were maintained in recipients, who also showed increased trabecular thickness of the regenerated periodontal bone (P < 0.05). These key genera were correlated with BV/TV and BV (P < 0.05). In addition, LGG gavage significantly regulated bone-related blood metabolites, of which selenomethionine promoted BMMSC osteogenesis. Notably, selenomethionine was associated with key gut genera (P < 0.05). Collectively, LGG improved periodontal bone regeneration in the context of periodontitis with hyperlipidemia by modulating gut microbiota and increasing pro-osteogenic metabolites in the blood. These results reveal new insights into the use of probiotics to promote periodontal bone regeneration via the gut-blood-bone axis.}, }
@article {pmid38195483, year = {2024}, author = {Zhao, T and Yu, Z}, title = {Modified Gexia-Zhuyu Tang inhibits gastric cancer progression by restoring gut microbiota and regulating pyroptosis.}, journal = {Cancer cell international}, volume = {24}, number = {1}, pages = {21}, pmid = {38195483}, issn = {1475-2867}, abstract = {BACKGROUND: Gexia-Zhuyu Tang (GZT), a traditional Chinese medicine formula, is used to treat a variety of diseases. However, its roles in gastric cancer (GC) remain unclear.<br><br>OBJECTIVE: The aim of this study was to explore the roles and underlying molecular mechanisms of modified GZT in GC.<br><br>METHODS: The effects of modified GZT on GC were investigated by constructing mouse xenograft models with MFC cell line. The fecal samples from low-dose, high-dose, and without modified GZT treatment groups were collected for the 16S rRNA gene sequencing and fecal microbiota transplantation (FMT). Histopathological alterations of mice were evaluated using the hematoxylin-eosin (HE). Immunohistochemical (IHC) analysis with Ki67 and GSDMD was performed to measure tissue cell proliferation and pyroptosis, respectively. Proteins associated with pyroptosis, invasion, and metastasis were detected by Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to assess inflammation-related factors levels.<br><br>RESULTS: Modified GZT inhibited GC tumor growth and reduced metastasis and invasion-related proteins expression levels, including CD147, VEGF, and MMP-9. Furthermore, it notably promoted caspase-1-dependent pyroptosis, as evidenced by a dose-dependent increase in TNF-&#x3b1;, IL-1&#x3b2;, IL-18, and LDH levels, along with elevated protein expression of NLRP3, ASC, and caspase-1. Additionally, modified GZT increased species abundance and diversity of the intestinal flora. FMT assay identified that modified GZT inhibited GC tumor progression through regulation of intestinal flora.<br><br>CONCLUSIONS: Modified GZT treatment may promote pyroptosis by modulating gut microbiota in GC. This study identifies a new potential approach for the GC clinical treatment.}, }
@article {pmid38195358, year = {2024}, author = {Andary, CM and Al, KF and Chmiel, JA and Gibbons, S and Daisley, BA and Parvathy, SN and Maleki Vareki, S and Bowdish, DME and Silverman, MS and Burton, JP}, title = {Dissecting mechanisms of fecal microbiota transplantation efficacy in disease.}, journal = {Trends in molecular medicine}, volume = {30}, number = {3}, pages = {209-222}, doi = {10.1016/j.molmed.2023.12.005}, pmid = {38195358}, issn = {1471-499X}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Clostridioides difficile ; *Microbiota ; *Clostridium Infections/therapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as an alternative or adjunct experimental therapy for microbiome-associated diseases following its success in the treatment of recurrent Clostridioides difficile infections (rCDIs). However, the mechanisms of action involved remain relatively unknown. The term 'dysbiosis' has been used to describe microbial imbalances in relation to disease, but this traditional definition fails to consider the complex cross-feeding networks that define the stability of the microbiome. Emerging research transitions toward the targeted restoration of microbial functional networks in treating different diseases. In this review, we explore potential mechanisms responsible for the efficacy of FMT and future therapeutic applications, while revisiting definitions of 'dysbiosis' in favor of functional network restoration in rCDI, inflammatory bowel diseases (IBDs), metabolic diseases, and cancer.}, }
@article {pmid38195204, year = {2024}, author = {Trøseid, M and Molinaro, A and Gelpi, M and Vestad, B and Kofoed, KF and Fuchs, A and Køber, L and Holm, K and Benfield, T and Ueland, PM and Hov, JR and Nielsen, SD and Knudsen, AD}, title = {Gut Microbiota Alterations and Circulating Imidazole Propionate Levels Are Associated With Obstructive Coronary Artery Disease in People With HIV.}, journal = {The Journal of infectious diseases}, volume = {229}, number = {3}, pages = {898-907}, pmid = {38195204}, issn = {1537-6613}, support = {//Rigshospitalet/ ; //Lundbeck Foundation/ ; //Novo Nordisk Foundation/ ; 2016004//South-Eastern Norway Regional Health Authority/ ; 240787/F20//Research Council of Norway/ ; }, mesh = {Humans ; HIV ; *HIV Infections/complications ; *Coronary Artery Disease ; *Gastrointestinal Microbiome ; Dysbiosis ; RNA, Ribosomal, 16S/genetics ; *Imidazoles ; }, abstract = {BACKGROUND: The impact of gut microbiota and its metabolites on coronary artery disease (CAD) in people with human immunodeficiency virus (PWH) is unknown. Emerging evidence suggests that imidazole propionate (ImP), a microbial metabolite, is linked with cardiometabolic diseases.<br><br>METHODS: Fecal samples from participants of the Copenhagen Comorbidity in HIV infection (COCOMO) study were processed for 16S rRNA sequencing and ImP measured with liquid chromatography-tandem mass spectrometry. CAD severity was investigated by coronary computed tomography-angiography, and participants grouped according to obstructive CAD (n = 60), nonobstructive CAD (n = 80), or no CAD (n = 114).<br><br>RESULTS: Participants with obstructive CAD had a gut microbiota with lower diversity and distinct compositional shift, with increased abundance of Rumiococcus gnavus and Veillonella, known producers of ImP. ImP plasma levels were associated with this dysbiosis, and significantly elevated in participants with obstructive CAD. However, gut dysbiosis but not plasma ImP was independently associated with obstructive CAD after adjustment for traditional and HIV-related risk factors (adjusted odds ratio, 2.7; 95% confidence interval, 1.1-7.2; P = .048).<br><br>CONCLUSIONS: PWH with obstructive CAD displays a distinct gut microbiota profile and increased circulating ImP plasma levels. Future studies should determine whether gut dysbiosis and related metabolites such as ImP are predictive of incident cardiovascular events.}, }
@article {pmid38194829, year = {2024}, author = {Liu, X and Wang, C and Li, Y and Wang, Y and Sun, X and Wang, Q and Luo, J and Lv, W and Yang, X and Liu, Y}, title = {Fecal microbiota transplantation revealed the function of folic acid on reducing abdominal fat deposition in broiler chickens mediated by gut microbiota.}, journal = {Poultry science}, volume = {103}, number = {3}, pages = {103392}, pmid = {38194829}, issn = {1525-3171}, mesh = {Animals ; Folic Acid/pharmacology ; Fecal Microbiota Transplantation/veterinary ; Chickens/physiology ; *Gastrointestinal Microbiome ; *Communicable Diseases/veterinary ; Abdominal Fat ; }, abstract = {Excess abdominal fat reduces carcass yield and feed conversion ratio, thereby resulting in significant economic losses in the poultry industry. Our previous study demonstrated that dietary addition of folic acid reduced fat deposition and changed gut microbiota and short-chain fatty acid. However, whether folic acid regulating abdominal fat deposition was mediated by gut microbiota was unclear. A total of 210 one-day-old broiler chickens were divided into 3 groups including the control (CON), folic acid (FA), and fecal microbiota transplantation (FMT) groups. From 14th day, broiler chickens in CON and FA groups were given perfusion administration with 1 mL diluent daily, while 1 mL fecal microbiota transplantation suspension from FA group prepared before was perfusion in FMT group receiving control diets. The result showed that abdominal fat percentage was significantly lower in FA and FMT groups when compared with CON group (P < 0.05). Morphology analysis revealed that the villus height of jejunum and ileum were significantly higher in FMT group (P < 0.05), and the villus height of jejunum was also significantly higher in FA group (P < 0.05), while the diameter and cross-sectional area (CSA) of adipocytes were significantly decreased in FA and FMT groups when compared with CON group (P < 0.05). Western blot results indicated that the expression levels of FOXO1 and PLIN1 in FMT group were significantly increased (P < 0.05), whereas the expression levels of PPARγ, C/EBPα, and FABP4 were significantly decreased (P < 0.05). Additionally, the Chao1, Observed-species, Shannon and Simpson indexes in FA and FMT groups were significantly higher (P < 0.05), but the microbiota were similar between FMT and FA groups (P < 0.05). LEfSe analysis determined that Lactobacillus, Clostridium and Dehalobacterium were found to be predominant in FA group, while Oscillospira, Shigella, and Streptococcus were the dominant microflora in FMT group. Furthermore, these cecal microbiota were mostly involved in infectious disease, cellular community prokaryotes, cell motility and signal transduction in FA group (P < 0.05), whereas functional capacities involved in signal transduction, cell motility, infectious disease and environment adaptation were enriched significantly of cecal microbiota in FMT group (P < 0.05). In summary, both fecal microbiota transplantation from the broiler chickens of dietary added folic acid and dietary folic acid addition effectively reduced abdominal fat deposition, indicating that the regulatory effect of folic acid on abdominal fat deposition was mediated partly by gut microbiota in broiler chickens.}, }
@article {pmid38194333, year = {2024}, author = {Birn, FH and Wester, SR and Andreasen, SE and Hvas, CL and Bager, P}, title = {Quality of life among older patients receiving faecal microbiota transplant for Clostridioides difficile infection.}, journal = {British journal of nursing (Mark Allen Publishing)}, volume = {33}, number = {1}, pages = {8-14}, doi = {10.12968/bjon.2024.33.1.8}, pmid = {38194333}, issn = {2052-2819}, mesh = {Humans ; Aged ; *Quality of Life ; Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; Health Personnel ; Patients ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has mainly been studied in quantitative research to investigate effect rates. However, there is a lack of qualitative studies to explore patient perspectives.<br><br>AIM: To explore perceptions of quality of life in older patients with Clostridioides difficile infection (CDI) at least 1 week after receiving FMT.<br><br>METHOD: A qualitative study examining quality of life for patients treated with FMT.<br><br>FINDINGS: Patients with a permanent or transient treatment effect experienced an increase in quality of life in the physical, psychological and social domains. However, patients who did not respond to the treatment experienced negative impacts on their psychological, physical, and social domains. Although patients found the content unappealing, none had reservations about receiving the treatment.<br><br>CONCLUSION: This study highlights the importance of considering the psychological, social and physical wellbeing of patients when assessing the efficacy of FMT as a treatment option for patients with CDI. It further emphasises the importance of health professionals identifying patients' individual ways of handling the disease and everyday life to improve their quality of life.}, }
@article {pmid38193712, year = {2024}, author = {Guo, H and Cui, J and Li, Q and Liang, X and Li, J and Yang, B and Kalds, P and Chen, Y and Yang, Y}, title = {A multi-omic assessment of the mechanisms of intestinal microbes used to treat diarrhea in early-weaned lambs.}, journal = {mSystems}, volume = {9}, number = {2}, pages = {e0095323}, pmid = {38193712}, issn = {2379-5077}, support = {2022YFD1300201//MOST | National Key Research and Development Program of China (NKPs)/ ; 2021YFD1600704//MOST | National Key Research and Development Program of China (NKPs)/ ; CARS-39-12//MOA | Earmarked Fund for China Agriculture Research System/ ; }, mesh = {Animals ; Sheep ; *Multiomics ; Weaning ; *Dietary Supplements ; Diarrhea/therapy ; Inflammation ; }, abstract = {Transplant of donor microbiota can significantly alter the structure of the host's intestinal microbiota and alleviate early weaning stress. Screening for alternative-resistant products by transplanting fecal bacteria from healthy lambs is a current research trend in the livestock industry. In the present study, fecal microbiota transplantation was performed in lambs with diarrhea during early weaning. The transplanted fecal microbiota greatly reduced the diarrhea and serum inflammatory factor levels caused by early weaning. Transcriptome sequencing revealed that fecal microbiota transplantation alleviated colonic inflammation and increased the expression of colonic ion transport proteins. In addition, the levels of Streptococcus, Enterococcus, and Escherichia Shigella decreased in the jejunum, cecum, and colon of the lambs; meanwhile, the levels of Bifidobacterium and multiple secondary bile acids, such as ursodeoxycholic acid, increased in the colon. Furthermore, the abundance of Bifidobacterium was significantly negatively correlated with the diarrhea index. The fecal microbiota transplantation reshaped the intestinal microbiota of early-weaned lambs, protected the intestinal physiology and immune barrier, and reduced weaning stress. In addition to making available bacteriological products for controlling intestinal inflammation in young lambs, this study offers a theoretical framework and technical system for the mechanisms by which microbiota transplantation regulates intestinal health in young lambs.IMPORTANCEBefore weaning, the digestive system of lambs is not well developed; hence, its resistance to infectious diseases is weak. Under intensive feeding systems, lambs can easily be stressed and the risk of bacterial infection is high, which causes diarrhea, which in turn may cause mortality and significant economic losses to the livestock industry. With the elimination of antibiotics in animal feed, the incidence of mortality due to intestinal illnesses in lambs has gradually increased. There are several types of probiotics routinely used in young animals, but the effects and processes of their usage have only been assessed in monogastric animals. The lack of data on ruminants, particularly sheep, has severely hampered the process of efficient and healthy sheep breeding. Therefore, there is an urgent need to identify effective and safe functional supplements for lambs.}, }
@article {pmid38193707, year = {2024}, author = {Ghosh, S and Erickson, D and Chua, MJ and Collins, J and Jala, VR}, title = {The microbial metabolite urolithin A reduces Clostridioides difficile toxin expression and toxin-induced epithelial damage.}, journal = {mSystems}, volume = {9}, number = {2}, pages = {e0125523}, pmid = {38193707}, issn = {2379-5077}, support = {P30 ES030283/ES/NIEHS NIH HHS/United States ; R21 AA030638/AA/NIAAA NIH HHS/United States ; P20 GM125504/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Bacterial Toxins/genetics ; Enterotoxins/genetics ; *Clostridioides difficile/metabolism ; Bacterial Proteins/genetics ; *Enterocolitis, Pseudomembranous/drug therapy ; *Clostridium Infections/drug therapy ; *Colitis/chemically induced ; *Coumarins ; }, abstract = {Clostridioides difficile is a Gram-positive, anaerobic, spore-forming bacterium responsible for antibiotic-associated pseudomembranous colitis. Clostridioides difficile infection (CDI) symptoms can range from diarrhea to life-threatening colon damage. Toxins produced by C. difficile (TcdA and TcdB) cause intestinal epithelial injury and lead to severe gut barrier dysfunction, stem cell damage, and impaired regeneration of the gut epithelium. Current treatment options for intestinal repair are limited. In this study, we demonstrate that treatment with the microbial metabolite urolithin A (UroA) attenuates CDI-induced adverse effects on the colon epithelium in a preclinical model of CDI-induced colitis. Moreover, our analysis suggests that UroA treatment protects against C. difficile-induced inflammation, disruption of gut barrier integrity, and intestinal tight junction proteins in the colon of CDI mice. Importantly, UroA treatment significantly reduced the expression and release of toxins from C. difficile without inducing bacterial cell death. These results indicate the direct regulatory effects of UroA on bacterial gene regulation. Overall, our findings reveal a novel aspect of UroA activity, as it appears to act at both the bacterial and host levels to protect against CDI-induced colitis pathogenesis. This research sheds light on a promising avenue for the development of novel treatments for C. difficile infection.IMPORTANCETherapy for Clostridioides difficile infections includes the use of antibiotics, immunosuppressors, and fecal microbiota transplantation. However, these treatments have several drawbacks, including the loss of colonization resistance, the promotion of autoimmune disorders, and the potential for unknown pathogens in donor samples. To date, the potential benefits of microbial metabolites in CDI-induced colitis have not been fully investigated. Here, we report for the first time that the microbial metabolite urolithin A has the potential to block toxin production from C. difficile and enhance gut barrier function to mitigate CDI-induced colitis.}, }
@article {pmid38193259, year = {2024}, author = {De Paepe, E and Plekhova, V and Vangeenderhuysen, P and Baeck, N and Bullens, D and Claeys, T and De Graeve, M and Kamoen, K and Notebaert, A and Van de Wiele, T and Van Den Broeck, W and Vanlede, K and Van Winckel, M and Vereecke, L and Elliott, C and Cox, E and Vanhaecke, L}, title = {Integrated gut metabolome and microbiome fingerprinting reveals that dysbiosis precedes allergic inflammation in IgE-mediated pediatric cow's milk allergy.}, journal = {Allergy}, volume = {79}, number = {4}, pages = {949-963}, doi = {10.1111/all.16005}, pmid = {38193259}, issn = {1398-9995}, support = {//Fonds Wetenschappelijk Onderzoek/ ; //Bijzonder Onderzoeksfonds UGent/ ; }, mesh = {Humans ; Child ; Child, Preschool ; Cattle ; Female ; Mice ; Animals ; *Milk Hypersensitivity ; Dysbiosis ; RNA, Ribosomal, 16S ; *Microbiota ; Inflammation ; Allergens ; Lactoglobulins ; Immunoglobulin E ; Metabolome ; }, abstract = {BACKGROUND: IgE-mediated cow's milk allergy (IgE-CMA) is one of the first allergies to arise in early childhood and may result from exposure to various milk allergens, of which β-lactoglobulin (BLG) and casein are the most important. Understanding the underlying mechanisms behind IgE-CMA is imperative for the discovery of novel biomarkers and the design of innovative treatment and prevention strategies.<br><br>METHODS: We report a longitudinal in&#xa0;vivo murine model, in which two mice strains (BALB/c and C57Bl/6) were sensitized to BLG using either cholera toxin or an oil emulsion (n&#x2009;=&#x2009;6 per group). After sensitization, mice were challenged orally, their clinical signs monitored, antibody (IgE and IgG1) and cytokine levels (IL-4 and IFN-&#x3b3;) measured, and fecal samples subjected to metabolomics. The results of the murine models were further extrapolated to fecal microbiome-metabolome data from our population of IgE-CMA (n&#x2009;=&#x2009;22) and healthy (n&#x2009;=&#x2009;23) children (Trial: NCT04249973), on which polar metabolomics, lipidomics and 16S rRNA metasequencing were performed. In&#xa0;vitro gastrointestinal digestions and multi-omics corroborated the microbial origin of proposed metabolic changes.<br><br>RESULTS: During mice sensitization, we observed multiple microbially derived metabolic alterations, most importantly bile acid, energy and tryptophan metabolites, that preceded allergic inflammation. We confirmed microbial dysbiosis, and its associated effect on metabolic alterations in our patient cohort, through in&#xa0;vitro digestions and multi-omics, which was accompanied by metabolic signatures of low-grade inflammation.<br><br>CONCLUSION: Our results indicate that gut dysbiosis precedes allergic inflammation and nurtures a chronic low-grade inflammation in children on elimination diets, opening important new opportunities for future prevention and treatment strategies.}, }
@article {pmid38193161, year = {2024}, author = {Margalit-Yehuda, R and Maradey-Romero, C and Davidov, Y and Ram, E and Carter, D}, title = {Comparison of etiological and physiological characteristics of fecal incontinence in men and women.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {326}, number = {3}, pages = {G274-G278}, doi = {10.1152/ajpgi.00113.2023}, pmid = {38193161}, issn = {1522-1547}, mesh = {Female ; Humans ; Male ; *Anal Canal/pathology ; Ataxia/complications ; *Fecal Incontinence/epidemiology/etiology ; Manometry ; *Rectum/pathology ; }, abstract = {Fecal incontinence (FI) is often underreported and underestimated in men. Our aims were to clarify the causes and the physiological characteristics of FI in men and to underline the differences between etiological and physiological factors in men and women diagnosed with FI. The study cohort encompassed 200 men and 200 women who underwent anatomical and physiological evaluation for FI in a tertiary referral center specializing in pelvic floor disorders. All patients underwent endoanal ultrasound and anorectal manometry. Evacuation proctography was performed in some patients. Demographic, medical, anatomical, and physiological parameters were compared between the two study groups. Urge incontinence was the most frequent type of FI in both genders. In men, anal fistula, history of anal surgeries, rectal tumors, and pelvic radiotherapy were common etiologic factors, whereas history of pelvic surgeries was more common in women. Associated urinary incontinence was reported more frequently by women. External anal sphincter defects, usually anterior, were more common in women (M: 1.5%, F: 24%, P < 0.0001), whereas internal anal sphincter defect prevalence was similar in men and women (M: 6%, F: 12%, P = 0.19). Decreased resting and squeeze pressures were less common in men (M: 29%, F: 46%, P < 0.0001: M: 44%, F: 66%, P < 0.0001). The incidence of rectal hyposensitivity was higher in men (M: 11.1%, F: 2.8%, P < 0.0001), whereas rectal hypersensitivity was higher in women (M: 5.8%, F: 10.8%, P < 0.0001). Anorectal dyssynergia was more common in men (M: 66%, F: 37%, P < 0.0001). Significantly different etiological factors and physiological characteristics for FI were found in men. Acknowledging these differences is significant and may yield better treatment options.NEW &amp; NOTEWORTHY Fecal incontinence (FI) in men has different etiological factors when compared with women. The prevalence of internal anal sphincter defect among men with FI was similar to women. Different manometric measurements were found among men with FI: decreased anal pressures were less common among men, whereas rectal hyposensitivity and anorectal dyssynergia were more common among men.}, }
@article {pmid38192292, year = {2023}, author = {Dai, W and Cai, D and Zhou, S and Li, A and Xie, J and Zhang, J}, title = {Uncovering a causal connection between the Lachnoclostridium genus in fecal microbiota and non-alcoholic fatty liver disease: a two-sample Mendelian randomization analysis.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1276790}, pmid = {38192292}, issn = {1664-302X}, abstract = {BACKGROUND: Previous observational studies have indicated that an imbalance in gut microbiota may contribute to non-alcoholic fatty liver disease (NAFLD). However, given the inevitable bias and unmeasured confounders in observational studies, the causal relationship between gut microbiota and NAFLD cannot be deduced. Therefore, we employed a two-sample Mendelian randomization (TSMR) study to assess the causality between gut microbiota and NAFLD.<br><br>METHODS: The gut microbiota-related genome-wide association study (GWAS) data of 18,340 individuals were collected from the International MiBioGen consortium. The GWAS summary data for NAFLD from the Anstee cohort (1,483 cases and 17,781 controls) and the FinnGen consortium (894 cases and 217,898 controls) were utilized in the discovery and verification phases, respectively. The inverse variance weighted (IVW) method was used as the principal method in our Mendelian randomization (MR) study, with sensitivity analyses using the MR-Egger, weighted median, simple mode, and weighted mode methods. The MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy. Moreover, a fixed-effect meta-analysis was conducted to verify the robustness of the results.<br><br>RESULTS: The gene prediction results showed that at the genus level, four gut microbiota were causally associated with NAFLD in the GWAS conducted by Anstee et al. The relative abundance of Intestinimonas (OR: 0.694, 95%CI: 0.533-0.903, p&#x2009;=&#x2009;0.006, IVW), Lachnoclostridium (OR: 0.420, 95%CI: 0.245-0.719, p&#x2009;=&#x2009;0.002, IVW), and Senegalimassilia (OR: 0.596, 95%CI: 0.363-0.978, p&#x2009;=&#x2009;0.041, IVW) was negatively associated with NAFLD. The relative abundance of Ruminococcus1 (OR: 1.852, 95%CI: 1.179-2.908, p&#x2009;=&#x2009;0.007, IVW) was positively correlated with NAFLD. Among them, the Lachnoclostridium genus was validated in FinnGen GWAS (OR: 0.53, 95%CI: 0.304-0.928, p&#x2009;=&#x2009;0.026, IVW). The Lachnoclostridium genus was also significantly associated with NAFLD risk in the meta-analyses (OR: 0.470, 95%CI: 0.319-0.692, p&#x2009;=&#x2009;0.0001, IVW). No heterogeneity or pleiotropy was observed.<br><br>CONCLUSION: This study provided new evidence of the relationship between the Lachnoclostridium genus and NAFLD, suggesting that augmentation of the relative abundance of the Lachnoclostridium genus through the oral administration of probiotics or fecal microbiota transplantation could be an effective way to reduce the risk of NAFLD.}, }
@article {pmid38191517, year = {2024}, author = {Ichikawa, M and Okada, H and Nakamoto, N and Taniki, N and Chu, PS and Kanai, T}, title = {The gut-liver axis in hepatobiliary diseases.}, journal = {Inflammation and regeneration}, volume = {44}, number = {1}, pages = {2}, pmid = {38191517}, issn = {1880-9693}, support = {JP21ek0109416//Japan Agency for Medical Research and Development/ ; }, abstract = {Recent advances in the analysis of intestinal bacteria have led to reports of variations in intestinal bacterial levels among hepatobiliary diseases. The mechanisms behind the changes in intestinal bacteria in various hepatobiliary diseases include the abnormal composition of intestinal bacteria, weakening of the intestinal barrier, and bacterial translocation outside the intestinal tract, along with their metabolites, but many aspects remain unresolved. Further research employing clinical studies and animal models is expected to clarify the direct relationship between intestinal bacteria and hepatobiliary diseases and to validate the utility of intestinal bacteria as a diagnostic biomarker and potential therapeutic target. This review summarizes the involvement of the microbiota in the pathogenesis of hepatobiliary diseases via the gut-liver axis.}, }
@article {pmid38191281, year = {2024}, author = {Tariq, R and Loftus, EV and Pardi, D and Khanna, S}, title = {Durability and outcomes of fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with moderate to severe inflammatory bowel disease.}, journal = {Intestinal research}, volume = {22}, number = {2}, pages = {208-212}, pmid = {38191281}, issn = {1598-9100}, support = {T32 DK007198/DK/NIDDK NIH HHS/United States ; DK07198/DK/NIDDK NIH HHS/United States ; }, }
@article {pmid38190716, year = {2024}, author = {Cao, Q and Zhao, M and Su, Y and Liu, S and Lin, Y and Da, H and Yue, C and Liu, Y and Jing, D and Zhao, Q and Liu, N and Du, J and Zuo, Z and Fu, Y and Chen, A and Birnbaumer, L and Yang, Y and Dai, B and Gao, X}, title = {Chronic Stress Dampens Lactobacillus Johnsonii-Mediated Tumor Suppression to Enhance Colorectal Cancer Progression.}, journal = {Cancer research}, volume = {84}, number = {5}, pages = {771-784}, doi = {10.1158/0008-5472.CAN-22-3705}, pmid = {38190716}, issn = {1538-7445}, support = {82072720//National Natural Science Foundation of China (NSFC)/ ; 82273329//National Natural Science Foundation of China (NSFC)/ ; 82273972//National Natural Science Foundation of China (NSFC)/ ; 82304551//National Natural Science Foundation of China (NSFC)/ ; 82002971//National Natural Science Foundation of China (NSFC)/ ; 2022ZB308//Jiangsu Funding Program for Excellent Postdoctoral Talent/ ; 2022M713478//China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)/ ; BK20231023//Natural Science Foundation of Jiangsu Province (Jiangsu Natural Science Foundation)/ ; 2022BEG02043//Key Research and Development Program of Ningxia Hui autonomous region/ ; Z01-ES-101684//Intramural Research Program of the NIH/ ; }, mesh = {Humans ; Animals ; Mice ; *Colorectal Neoplasms/metabolism ; beta Catenin/genetics ; *Lactobacillus johnsonii/genetics ; RNA, Ribosomal, 16S/genetics ; *Gastrointestinal Microbiome ; }, abstract = {UNLABELLED: Colorectal cancer development and outcome are impacted by modifiable risk factors, including psychologic stress. The gut microbiota has also been shown to be linked to psychologic factors. Here, we found a marked deteriorative effect of chronic stress in multiple colorectal cancer models, including chemically induced (AOM/DSS), genetically engineered (APCmin/+), and xenograft tumor mouse models. RNA sequencing data from colon tissues revealed that expression of stemness-related genes was upregulated in the stressed colorectal cancer group by activated β-catenin signaling, which was further confirmed by results from ex vivo organoid analyses as well as in vitro and in vivo cell tumorigenicity assays. 16S rRNA sequencing of the gut microbiota showed that chronic stress disrupted gut microbes, and antibiotic treatment and fecal microbiota transplantation abolished the stimulatory effects of chronic stress on colorectal cancer progression. Stressed colorectal cancer mice displayed a significant decrease in Lactobacillus johnsonii (L. johnsonii) abundance, which was inversely correlated with tumor load. Moreover, protocatechuic acid (PCA) was identified as a beneficial metabolite produced by L. johnsonii based on metabolome sequencing and LC/MS-MS analysis. Replenishment of L. johnsonii or PCA blocked chronic stress-induced colorectal cancer progression by decreasing β-catenin expression. Furthermore, PCA activated the cGMP pathway, and the cGMP agonist sildenafil abolished the effects of chronic stress on colorectal cancer. Altogether, these data identify that stress impacts the gut microbiome to support colorectal cancer progression.<br><br>SIGNIFICANCE: Chronic stress stimulates cancer stemness by reducing the intestinal abundance of L. johnsonii and its metabolite PCA to enhance &#x3b2;-catenin signaling, forming a basis for potential strategies to circumvent stress-induced cancer aggressiveness. See related commentary by McCollum and Shah, p. 645.}, }
@article {pmid38188335, year = {2023}, author = {Hu, Y and Hu, C and Jiang, J and Zhang, J and Li, Y and Peng, Z}, title = {Clostridioides difficile infection after extracorporeal membrane oxygenation support for acute myocardial infarction: a case report.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1333209}, pmid = {38188335}, issn = {2296-858X}, abstract = {INTRODUCTION: Restored cardiopulmonary function is efficiently achieved by utilizing extracorporeal membrane oxygenation (ECMO). Nevertheless, the incidence of Clostridioides difficile infection (CDI) associated with ECMO is relatively uncommon.<br><br>CASE PRESENTATION: In this report, we present the case of a 59-year-old male with severe chest pain due to acute myocardial infarction, subsequently necessitating ECMO support. During the first day of hospitalization, pulmonary infections were observed, and piperacillin-tazobactam was prescribed for 7&#x2009;days at low dosages. However, the patient developed severe diarrhea 4&#x2009;days later. After ruling out common pathogens, we suspected the occurrence of CDI and performed genetic testing for C. difficile toxin, confirming our diagnosis. The prescription of vancomycin resulted in slight improvement, while fecal microbiota transplantation (FMT) proved to be more effective.<br><br>CONCLUSION: In this case, temporary application of ECMO was applied, and the anti-infective treatment relied on the use of antibiotics at short-term, low-dose, and low CDI risk. Hence, the occurrence of CDI was considered an uncommon event, which may serve as a reference for future cases.}, }
@article {pmid38187130, year = {2023}, author = {Zhang, R and Qiu, W and Sun, X and Li, J and Geng, X and Yu, S and Liu, Y and Huang, H and Li, M and Fan, Z and Li, M and Lv, G}, title = {Gut microbiota dynamics in a 1-year follow-up after adult liver transplantation in Northeast China.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1266635}, pmid = {38187130}, issn = {1664-042X}, abstract = {Background: Liver transplantation (LTx) is the most effective treatment for end-stage liver diseases. Gut microorganisms influence the host physiology. We aim to profile the dynamics of gut microbiota in the perioperative period and a 1-year follow-up of LTx recipients in Northeast China. Methods: A total of 257 fecal samples were longitudinally collected from 85 LTx patients using anal swabs from pre-LTx to 1-year post-LTx. A total of 48 fecal samples from end-stage liver disease patients without LTx served as the control. 16S rRNA sequencing was used to analyze gut microbiota diversity, bacterial genera, phenotype classification, and metabolic pathways. Results: The diversity of gut microbiota decreased significantly after transplantation, accompanied by a profound change in the microbial structure, which is characterized by increased abundance of facultative anaerobic bacteria dominated by g_Enterococcus and reduced anaerobic bacteria composition. Predicted functional analysis also revealed disturbances in the metabolic pathway of the gut microbiota. After LTx, the diversity of microbiota gradually recovered but to a less preoperative level after 1 year of recovery. Compared with pre-transplantation, the microbiome structure was characterized by an increase in Acidaminococcus and Acidithiobacillus after 1 year of transplantation. Conclusion: LTx and perioperative treatment triggered gut microbial dysbiosis. The gut microbiota was restructured after LTx to near to but significantly differed from that of pre-LTx.}, }
@article {pmid38184271, year = {2024}, author = {Yang, T and Qin, N and Liu, F and Zhao, Y and Liu, W and Fan, D}, title = {Berberine regulates intestinal microbiome and metabolism homeostasis to treat ulcerative colitis.}, journal = {Life sciences}, volume = {338}, number = {}, pages = {122385}, doi = {10.1016/j.lfs.2023.122385}, pmid = {38184271}, issn = {1879-0631}, mesh = {Mice ; Animals ; *Colitis, Ulcerative/drug therapy ; *Berberine/pharmacology/therapeutic use ; *Gastrointestinal Microbiome ; Inflammation ; Homeostasis ; *Colitis ; Dextran Sulfate/pharmacology ; }, abstract = {AIMS: This study aims to investigate the effects of berberine (BBR) on the intestinal microbiome (IM) and serum metabolome in ulcerative colitis (UC). Furthermore, the underlying molecular mechanisms of BBR in treating UC also will be explored systematically.<br><br>MATERIALS AND METHODS: A multi-omics approach that integrates the 16s rDNA, serum metabolome, transcriptomics and bioinformatics was profiled to investigate the potential effects of BBR on the IM, serum metabolites and metabolic pathways, and gene expression. In addition, BBR-induced fecal microbiota transplantation (BBR_FMT) was conducted in pseudo germ-free mice combined with the UC model to explore the effects of the IM on metabolic pathways and gene expression. The results of the transcriptomics and metabolic pathway-related genes were further examined by real-time PCR and western blot.<br><br>KEY FINDINGS: BBR ameliorated the community of IM and significantly promoted the abundance of f__Muribaculaceae, Bacteroides, Dubosiella, Allobaculum and Akkermansia. The metabolic profiles in UC mice were significantly modulated by BBR treatment. Furthermore, the inflammation-related metabolites and metabolic pathways in serum were negatively correlated with the abundance of Bacteroides and Akkermansia, which were induced by BBR treatment. BBR_FMT significantly inhibited the arachidonic acid (AA) metabolism pathway and its multiple markers with the mediation of the IM.<br><br>SIGNIFICANCE: BBR ameliorated serum metabolic homeostasis by regulating the IM. The inhibition of the AA metabolism pathway and its multiple markers was one of the mechanisms of BBR in the treatment of UC.}, }
@article {pmid38184214, year = {2024}, author = {Ji, H and Feng, S and Liu, Y and Cao, Y and Lou, H and Li, Z}, title = {Effect of GVHD on the gut and intestinal microflora.}, journal = {Transplant immunology}, volume = {82}, number = {}, pages = {101977}, doi = {10.1016/j.trim.2023.101977}, pmid = {38184214}, issn = {1878-5492}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/diagnosis/therapy/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Epithelial Cells/metabolism ; Anti-Bacterial Agents ; }, abstract = {Graft-versus-host disease (GVHD) is one of the most important cause of death in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The gastrointestinal tract is one of the most common sites affected by GVHD. However, there is no gold standard clinical practice for diagnosing gastrointestinal GVHD (GI-GVHD), and it is mainly diagnosed by the patient's clinical symptoms and related histological changes. Additionally, GI-GVHD causes intestinal immune system disorders, damages intestinal epithelial tissue such as intestinal epithelial cells((IEC), goblet, Paneth, and intestinal stem cells, and disrupts the intestinal epithelium's physical and chemical mucosal barriers. The use of antibiotics and diet alterations significantly reduces intestinal microbial diversity, further reducing bacterial metabolites such as short-chain fatty acids and indole, aggravating infection, and GI-GVHD. gut microbe diversity can be restored by fecal microbiota transplantation (FMT) to treat refractory GI-GVHD. This review article focuses on the clinical diagnosis of GI-GVHD and the effect of GVHD on intestinal flora and its metabolites.}, }
@article {pmid38184015, year = {2024}, author = {Wang, Y and Zhang, X and Yao, Y and Hu, S and Wang, W and Wang, D and Huang, C and Liu, H and Zhang, Q and He, T and Wang, S and Wu, Z and Jiang, R and Yang, C}, title = {Inferior social hierarchy is vulnerable to anxiety-like behavior in chronic pain mice: Potential role of gut microbiota and metabolites.}, journal = {Neurobiology of disease}, volume = {191}, number = {}, pages = {106402}, doi = {10.1016/j.nbd.2024.106402}, pmid = {38184015}, issn = {1095-953X}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/genetics ; Depression ; *Chronic Pain ; RNA, Ribosomal, 16S ; Hierarchy, Social ; Anxiety ; }, abstract = {Social dominance is a universal phenomenon among grouped animals that profoundly affects survival, health, and reproductive success by determining access to resources, and exerting a powerful influence on subsequent behavior. However, the understanding of pain and anxiety comorbidities in dominant or subordinate animals suffering from chronic pain is not well-defined. Here, we provide evidence that subordinate mice are more susceptible to pain-induced anxiety compared to dominant mice. We propose that the gut microbiota may play a mediating role in this mechanism. Our findings demonstrate that transplantation of fecal microbiota from subordinate mice with chronic inflammatory pain, but not dominant mice, into antibiotics-treated pseudo-germ-free mice significantly amplifies anxiety-like phenotypes, highlighting the critical involvement of gut microbiota in this behavioral response. Using chronic inflammatory pain model, we carried out 16S rRNA sequencing and untargeted metabolomic analyses to explore the relationship between microbiota and metabolites in a stable social hierarchy of mice. Interestingly, anxiety-like behaviors were directly associated with some microbial genera and metabolites, especially bile acid metabolism. Overall, we have demonstrated a close relationship between social status and anxiety susceptibility, highlighting the contributions of gut microbiota and the associated metabolites in the high-anxiety state of subordinate mice with chronic inflammatory pain.}, }
@article {pmid38183474, year = {2024}, author = {Lin, QY and Du, JJ and Xu, H and Lv, MK and Xu, L and Li, J and Cao, ZH}, title = {Effects of fecal microbial transplantation on police performance and transportation stress in Kunming police dogs.}, journal = {Applied microbiology and biotechnology}, volume = {108}, number = {1}, pages = {46}, pmid = {38183474}, issn = {1432-0614}, support = {202305AC160040//Yunnan Provincial Middle-Young Academic and Technical Leader Candidate/ ; YNWR-QNBJ-2018-137//Young Top-notch Talent of Yunnan Xingdian Support Project for High Level Talents/ ; }, mesh = {Dogs ; Animals ; *Fecal Microbiota Transplantation ; *Working Dogs ; Feces ; Bifidobacterium ; Diarrhea ; }, abstract = {Fecal microbiota transplantation (FMT) has been shown to improve gut dysbiosis in dogs; however, it has not completely been understood in police dogs. This study aimed to investigate the effects of FMT on performance and gut microflora in Kunming police dogs. Twenty Wolf Cyan dogs were randomly assigned to receive physiological saline or fecal suspension at low, medium, or high doses through oral gavage for 14 days. Growth performance, police performance, serum biochemical profiling, and gut microflora were determined 2-week post-FMT. Dogs after FMT treatment were also subjected to an hour road transportation and then were evaluated for serum stress indicators. Overall, FMT enhanced the growth performance and alleviated diarrhea rate in Kunming dogs with the greatest effects occurring in the low dose FMT (KML) group. The improvement of FMT on police performance was also determined. These above alterations were accompanied by changed serum biochemical parameters as indicated by elevated total protein and albumin and reduced total cholesterol and glycerol. Furthermore, the serum stress indicators after road transportation in dog post-FMT significantly decreased. Increased bacterial diversity and modified bacterial composition were found in the feces of dogs receiving FMT. The fecal samples from FMT dogs were characterized by higher abundances of the genera Lactobacillus, Prevotella, and Fusobacterium and lower concentrations of Cetobacterium, Allobaculum, Bifidobacterium, and Streptococcus. The present study supports a potential benefit of FMT on police performance in Kunming dogs. KEY POINTS: • FMT improves the growth performance and reduces diarrhea rates in Kunming police dogs. • FMT alleviates the serum stress profiles after road transportation in Kunming police dogs. • FMT modifies the gut microbiota composition of Kunming police dogs.}, }
@article {pmid38183010, year = {2024}, author = {Pourali, G and Kazemi, D and Chadeganipour, AS and Arastonejad, M and Kashani, SN and Pourali, R and Maftooh, M and Akbarzade, H and Fiuji, H and Hassanian, SM and Ghayour-Mobarhan, M and Ferns, GA and Khazaei, M and Avan, A}, title = {Microbiome as a biomarker and therapeutic target in pancreatic cancer.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {16}, pmid = {38183010}, issn = {1471-2180}, mesh = {Humans ; *Pancreatic Neoplasms/diagnosis/therapy ; Biomarkers ; *Microbiota ; Anti-Bacterial Agents ; Dysbiosis/therapy ; Tumor Microenvironment ; }, abstract = {Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC.}, }
@article {pmid38182136, year = {2024}, author = {Frishman, S and Nuriel-Ohayon, M and Turjeman, S and Pinto, Y and Yariv, O and Tenenbaum-Gavish, K and Peled, Y and Poran, E and Pardo, J and Chen, R and Muller, E and Borenstein, E and Hod, M and Louzoun, Y and Schwartz, B and Hadar, E and Collado, MC and Koren, O}, title = {Positive effects of diet-induced microbiome modification on GDM in mice following human faecal transfer.}, journal = {Gut}, volume = {73}, number = {10}, pages = {e17}, pmid = {38182136}, issn = {1468-3288}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Mice ; Humans ; Female ; *Gastrointestinal Microbiome/physiology ; Pregnancy ; Diet ; Feces/microbiology ; Disease Models, Animal ; }, }
@article {pmid38181823, year = {2024}, author = {Zheng, C and Wang, L and Zou, T and Lian, S and Luo, J and Lu, Y and Hao, H and Xu, Y and Xiang, Y and Zhang, X and Xu, G and Zou, X and Jiang, R}, title = {Ileitis promotes MASLD progression via bile acid modulation and enhanced TGR5 signaling in ileal CD8[+] T cells.}, journal = {Journal of hepatology}, volume = {80}, number = {5}, pages = {764-777}, doi = {10.1016/j.jhep.2023.12.024}, pmid = {38181823}, issn = {1600-0641}, mesh = {Mice ; Animals ; Bile Acids and Salts ; Interleukin-10 ; CD8-Positive T-Lymphocytes ; *Ileitis ; Signal Transduction/genetics ; Ileum ; *Fatty Liver ; *Crohn Disease ; Mice, Knockout ; TOR Serine-Threonine Kinases ; }, abstract = {BACKGROUND &amp; AIMS: Clinical evidence substantiates a link between inflammatory bowel disease, particularly Crohn's disease (CD), and metabolic dysfunction-associated steatotic liver disease (MASLD). This study aims to explore the underlying molecular mechanisms responsible for this association.<br><br>METHODS: MASLD was induced by administering high-fat and western diets, while inflammatory bowel disease was induced using DSS (dextran sulfate sodium) and the Il10 knockout (KO) mouse model. The investigation into the role of secondary bile acids (SBAs) in ileitis involved employing metagenomic sequencing, conducting metabolomics detection, performing fecal microbiota transplantation, and constructing CD8[+] T cell-specific gene knockout mice.<br><br>RESULTS: In MASLD+DSS and Il10 KO MASLD mice, we observed ileitis characterized by T-cell infiltration and activation in the terminal ileum. This condition resulted in decreased bile acid levels in the portal vein and liver, inhibited hepatic farnesoid X receptor (FXR) activation, and exacerbated MASLD. Metagenomic and metabolomic analysis of ileal contents revealed increased Clostridium proliferation and elevated SBA levels in MASLD-associated ileitis. Experiments using germ-free mice and fecal microbiota transplantation suggested an association between SBA and MASLD-related ileitis. In&#xa0;vitro, SBAs promoted CD8[+] T-cell activation via the TGR5, mTOR, and oxidative phosphorylation pathways. In&#xa0;vivo, TGR5 KO in CD8[+] T cells effectively alleviated ileitis and reversed the MASLD phenotype. Clinical data further supported these findings, demonstrating a positive correlation between ileitis and MASLD.<br><br>CONCLUSION: MASLD-induced changes in intestinal flora result in elevated levels of SBAs in the ileum. In the presence of a compromised intestinal barrier, this leads to severe CD8[+] T cell-mediated ileitis through the TGR5/mTOR/oxidative phosphorylation signaling pathway. Ileitis-induced tissue damage impairs enterohepatic circulation, inhibits hepatic FXR activation, and exacerbates the MASLD phenotype.<br><br>IMPACT AND IMPLICATIONS: Our study provides a comprehensive investigation of the interplay and underlying mechanisms connecting ileitis and metabolic dysfunction-associated steatotic liver disease (MASLD). Secondary bile acids produced by intestinal bacteria act as the critical link between MASLD and ileitis. Secondary bile acids exert their influence by disrupting liver lipid metabolism through the promotion of CD8[+] T cell-mediated ileitis. In future endeavors to prevent and treat MASLD, it is essential to thoroughly account for the impact of the intestinal tract, especially the ileum, on liver function via the enterohepatic circulation.}, }
@article {pmid38180642, year = {2024}, author = {Theofilis, P and Vlachakis, PK and Oikonomou, E and Tsioufis, K and Tousoulis, D}, title = {Targeting the Gut Microbiome to Treat Cardiometabolic Disease.}, journal = {Current atherosclerosis reports}, volume = {26}, number = {2}, pages = {25-34}, pmid = {38180642}, issn = {1534-6242}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/therapy ; Prebiotics ; *Probiotics/therapeutic use ; *Cardiovascular Diseases/therapy ; }, abstract = {PURPOSE OF REVIEW: Cardiometabolic diseases, which include obesity, type 2 diabetes, and cardiovascular diseases, constitute a worldwide health crisis of unparalleled proportions. The human gut microbiota has emerged as a prominent topic of inquiry in the search for novel treatment techniques. This review summarizes current research on the potential of addressing the gut microbiota to treat cardiometabolic disease.<br><br>RECENT FINDINGS: Recent studies have highlighted a complex link between the gut microbiota and host physiology, shedding light on the several processes through which gut microorganisms impact metabolic health, inflammation, and cardiovascular function. Furthermore, a growing corpus of research is available on microbiome-based therapies such as dietary interventions, probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. These therapies show promise as methods for reshaping the gut microbiota and, as a result, improving cardiometabolic outcomes. However, hurdles remain, ranging from the intricacies of microbiome research to the necessity for tailored treatments that take individual microbial variations into consideration, emphasizing the significance of furthering research to bridge the gap between microbiome science and clinical practice. The gut microbiome is a beacon of hope for improving the management of cardiometabolic disease in the age of precision medicine, since its association with their pathophysiology is constantly being unraveled and strengthened. Available studies point to the potential of gut microbiome-based therapeutics, which remains to be tested in appropriately designed clinical trials. Further preclinical research is, however, essential to provide answers to the existing obstacles, with the ultimate goal of enhancing patient care.}, }
@article {pmid38176929, year = {2023}, author = {Zhang, W and Ye, Y and Song, J and Sang, T and Xia, T and Xie, L and Qiu, X and Zeng, Q and Luo, X}, title = {Research Progress of Microbiota-Gut-Brain Axis in Parkinson's Disease.}, journal = {Journal of integrative neuroscience}, volume = {22}, number = {6}, pages = {157}, doi = {10.31083/j.jin2206157}, pmid = {38176929}, issn = {0219-6352}, mesh = {Humans ; *Parkinson Disease/therapy ; Brain-Gut Axis ; *Gastrointestinal Microbiome ; *Probiotics ; Brain/pathology ; }, abstract = {Parkinson's disease (PD) is a common neurodegenerative disorder characterized by misfolding of α-synuclein. Clinical manifestations include slowly developing resting tremor, muscle rigidity, bradykinesia and abnormal gait. The pathological mechanisms underlying PD are complex and yet to be fully elucidated. Clinical studies suggest that the onset of gastrointestinal symptoms may precede motor symptoms in PD patients. The microbiota-gut-brain axis plays a bidirectional communication role between the enteric nervous system and the central nervous system. This bidirectional communication between the brain and gut is influenced by the neural, immune and endocrine systems related to the gut microbiome. A growing body of evidence indicates a strong link between dysregulation of the gut microbiota and PD. In this review, we present recent progress in understanding the relationship between the microbiota-gut-brain axis and PD. We focus on the role of the gut microbiota, the unique changes observed in the microbiome of PD patients, and the impact of these changes on the progression of PD. Finally, we evaluate the role of current treatment strategies for PD, including probiotics, fecal microbial transplants, dietary modifications, and related drug therapies.}, }
@article {pmid38176570, year = {2024}, author = {He, H and Zhao, Z and Xiao, C and Li, L and Liu, YE and Fu, J and Liao, H and Zhou, T and Zhang, J}, title = {Gut microbiome promotes mice recovery from stress-induced depression by rescuing hippocampal neurogenesis.}, journal = {Neurobiology of disease}, volume = {191}, number = {}, pages = {106396}, doi = {10.1016/j.nbd.2023.106396}, pmid = {38176570}, issn = {1095-953X}, mesh = {Humans ; Mice ; Animals ; *Depression/metabolism ; *Gastrointestinal Microbiome/genetics ; Temozolomide/metabolism/pharmacology ; Hippocampus/metabolism ; Neurogenesis ; Stress, Psychological/psychology ; }, abstract = {Studies from rodents to primates and humans indicate that individuals vary in how resilient they are to stress, and understanding the basis of these variations may help improve treatments for depression. Here we explored the potential contribution of the gut microbiome to such variation. Mice were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks then allowed to recover for 3 weeks, after which they were subjected to behavioral tests and categorized as showing low or high stress resilience. The two types of mouse were compared in terms of hippocampal gene expression using RNA sequencing, fecal microbiomes using 16S RNA sequencing, and extent of neurogenesis in the hippocampus using immunostaining of brain sections. Fecal microbiota were transplanted from either type of mouse into previously stress-exposed and stress-naïve animals, and the effects of the transplantation on stress-induced behaviors and neurogenesis in the hippocampus were examined. Finally, we blocked neurogenesis using temozolomide to explore the role of neurogenesis promoted by fecal microbiota transplantation in enhancing resilience to stress. Results showed that highly stress-resilient mice, but not those with low resilience, improved significantly on measures of anhedonia, behavioral despair, and anxiety after 3-week recovery from CUMS. Their feces showed greater abundance of Lactobacillus, Bifidobacterium and Romboutsia than feces from mice with low stress resilience, as well as lower abundance of Staphylococcus, Psychrobacter and Corynebacterium. Similarly, highly stress-resilient mice showed greater neurogenesis in hippocampus than animals with low stress resilience. Transplanting fecal microbiota from mice with high stress resilience into previously CUMS-exposed recipients rescued neurogenesis in hippocampus, facilitating recovery from stress-induced depression and cognitive decline. Blockade of neurogenesis with temozolomide abolished recovery of recipients from CUMS-induced depression and cognitive decline in mice transplanted with fecal microbiota from mice with high stress resilience. In conclusion, our results suggested that remodeling of the gut microbiome after stress may reverse stress-induced impairment of hippocampal neurogenesis and thereby promote recovery from stress-induced depression.}, }
@article {pmid38175474, year = {2024}, author = {Campidelli, C and Bruxelle, JF and Collignon, A and Péchiné, S}, title = {Immunization Strategies Against Clostridioides difficile.}, journal = {Advances in experimental medicine and biology}, volume = {1435}, number = {}, pages = {117-150}, pmid = {38175474}, issn = {0065-2598}, mesh = {Animals ; Humans ; *Clostridioides difficile ; Immunization ; Vaccination ; Immunization, Passive ; Virulence Factors ; }, abstract = {Clostridioides difficile (C. difficile) infection (CDI) is an important healthcare but also a community-associated disease. CDI is considered a public health threat and an economic burden. A major problem is the high rate of recurrences. Besides classical antibiotic treatments, new therapeutic strategies are needed to prevent infection, to treat patients, and to prevent recurrences. If fecal transplantation has been recommended to treat recurrences, another key approach is to elicit immunity against C. difficile and its virulence factors. Here, after a summary concerning the virulence factors, the host immune response against C. difficile, and its role in the outcome of disease, we review the different approaches of passive immunotherapies and vaccines developed against CDI. Passive immunization strategies are designed in function of the target antigen, the antibody-based product, and its administration route. Similarly, for active immunization strategies, vaccine antigens can target toxins or surface proteins, and immunization can be performed by parenteral or mucosal routes. For passive immunization and vaccination as well, we first present immunization assays performed in animal models and second in humans and associated clinical trials. The different studies are presented according to the mode of administration either parenteral or mucosal and the target antigens and either toxins or colonization factors.}, }
@article {pmid38175472, year = {2024}, author = {Porcari, S and Maida, M and Bibbò, S and McIlroy, J and Ianiro, G and Cammarota, G}, title = {Fecal Microbiota Transplantation as Emerging Treatment in European Countries 2.0.}, journal = {Advances in experimental medicine and biology}, volume = {1435}, number = {}, pages = {85-99}, pmid = {38175472}, issn = {0065-2598}, mesh = {Humans ; Fecal Microbiota Transplantation ; Feces ; Anti-Bacterial Agents ; *Cross Infection ; *Inflammatory Bowel Diseases/therapy ; }, abstract = {Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections and one of the leading causes of morbidity and mortality in hospitalized patients in the world. Although several antibiotics effectively treat CDI, some individuals may not respond to these drugs and may be cured by transplanting stool from healthy donors. FMT has demonstrated extraordinary cure rates for the cure of CDI recurrences.Moreover, FMT has also been investigated in other disorders associated with the alteration of gut microbiota, such as inflammatory bowel disease (IBD), where the alterations of the gut microbiota ecology have been theorized to play a causative role. Although FMT is currently not recommended to cure IBD patients in clinical practice, several studies have been recently carried out with the ultimate goal to search new therapeutic options to patients.This review summarizes data on the use of FMT for the treatment of both CDI and IBD, with a special attention to highlight studies conducted in European countries.}, }
@article {pmid38175471, year = {2024}, author = {Fitzpatrick, F and Brennan, R and van Prehn, J and Skally, M and Brady, M and Burns, K and Rooney, C and Wilcox, MH}, title = {European Practice for CDI Treatment.}, journal = {Advances in experimental medicine and biology}, volume = {1435}, number = {}, pages = {57-84}, pmid = {38175471}, issn = {0065-2598}, mesh = {Humans ; Fidaxomicin ; *Metronidazole ; Vancomycin ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy ; }, abstract = {Clostridioides difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) management guidance for CDI were updated in 2021. This guidance document outlines the treatment options for a variety of CDI clinical scenarios and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). One of the main changes is that metronidazole is no longer recommended as first-line CDI treatment. Rather, fidaxomicin is preferred on the basis of reduced recurrence rates with vancomycin as an acceptable alternative. Recommended options for recurrent CDI now include bezlotoxumab as well as FMT.A 2017 survey of 20 European countries highlighted variation internationally in CDI management strategies. A variety of restrictions were in place in 65% countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. This survey was repeated in November 2022 to assess the current landscape of CDI management practices in Europe. Of 64 respondents from 17 countries, national CDI guidelines existed in 14 countries, and 11 have already/plan to incorporate the ESCMID 2021 CDI guidance, though implementation has not been surveyed in 6. Vancomycin is the most commonly used first-line agent for the treatment of CDI (n = 42, 66%), followed by fidaxomicin (n = 30, 47%). Six (9%) respondents use metronidazole as first-line agent for CDI treatment, whereas 22 (34%) only in selected low-risk patient groups. Fidaxomicin is more likely to be used in high-risk patient groups. Availability of anti-CDI therapy influenced prescribing in six respondents (9%). Approval pre-prescription was required before vancomycin (n = 3, 5%), fidaxomicin (n = 10, 6%), bezlotoxumab (n = 11, 17%) and FMT (n = 10, 6%). Implementation of CDI guidelines is rarely audited.Novel anti-CDI agents are being evaluated; it is not yet clear what will be the roles of these agents. The treatment of recurrent CDI is particularly troublesome, and several different live biotherapeutics are being developed, in addition to FMT.}, }
@article {pmid38174845, year = {2024}, author = {Liu, YH and Chen, J and Chen, X and Liu, H}, title = {Factors of faecal microbiota transplantation applied to cancer management.}, journal = {Journal of drug targeting}, volume = {32}, number = {2}, pages = {101-114}, doi = {10.1080/1061186X.2023.2299724}, pmid = {38174845}, issn = {1029-2330}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Treatment Outcome ; *Gastrointestinal Microbiome ; *Neoplasms/therapy ; }, abstract = {The homeostasis of the microbiota is essential for human health. In particular, the gut microbiota plays a critical role in the regulation of the immune system. Thus, faecal microbiota transplantation (FMT), a technology that has rapidly developed in the last decade, has specifically been utilised for the treatment of intestinal inflammation and has recently been found to be able to treat tumours in combination with immunotherapy. FMT has become a breakthrough in enhancing the response rate to immunotherapy in cancer patients by altering the composition of the patient's gut microbiota. This review discusses the mechanisms of faecal microorganism effects on tumour development, drug treatment efficacy, and adverse effects and describes the recent clinical research trials on FMT. Moreover, the factors influencing the efficacy and safety of FMT are described. We summarise the possibilities of faecal transplantation in the treatment of tumours and its complications and propose directions to explore the development of FMT.}, }
@article {pmid38173790, year = {2023}, author = {Jia, X and Chen, Q and Zhang, Y and Asakawa, T}, title = {Multidirectional associations between the gut microbiota and Parkinson's disease, updated information from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1296713}, pmid = {38173790}, issn = {2235-2988}, mesh = {Animals ; Humans ; Mice ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Parkinson Disease ; }, abstract = {The human gastrointestinal tract is inhabited by a diverse range of microorganisms, collectively known as the gut microbiota, which form a vast and complex ecosystem. It has been reported that the microbiota-gut-brain axis plays a crucial role in regulating host neuroprotective function. Studies have shown that patients with Parkinson's disease (PD) have dysbiosis of the gut microbiota, and experiments involving germ-free mice and fecal microbiota transplantation from PD patients have revealed the pathogenic role of the gut microbiota in PD. Interventions targeting the gut microbiota in PD, including the use of prebiotics, probiotics, and fecal microbiota transplantation, have also shown efficacy in treating PD. However, the causal relationship between the gut microbiota and Parkinson's disease remains intricate. This study reviewed the association between the microbiota-gut-brain axis and PD from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway. We found that the interactions among gut microbiota and PD are very complex, which should be "multidirectional", rather than conventionally regarded "bidirectional". To realize application of the gut microbiota-related mechanisms in the clinical setting, we propose several problems which should be addressed in the future study.}, }
@article {pmid38172339, year = {2024}, author = {Thiele Orberg, E and Meedt, E and Hiergeist, A and Xue, J and Heinrich, P and Ru, J and Ghimire, S and Miltiadous, O and Lindner, S and Tiefgraber, M and Göldel, S and Eismann, T and Schwarz, A and Göttert, S and Jarosch, S and Steiger, K and Schulz, C and Gigl, M and Fischer, JC and Janssen, KP and Quante, M and Heidegger, S and Herhaus, P and Verbeek, M and Ruland, J and van den Brink, MRM and Weber, D and Edinger, M and Wolff, D and Busch, DH and Kleigrewe, K and Herr, W and Bassermann, F and Gessner, A and Deng, L and Holler, E and Poeck, H}, title = {Bacteria and bacteriophage consortia are associated with protective intestinal metabolites in patients receiving stem cell transplantation.}, journal = {Nature cancer}, volume = {5}, number = {1}, pages = {187-208}, pmid = {38172339}, issn = {2662-1347}, support = {360372040, 395357507, 324392634//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 70114547//Deutsche Krebshilfe (German Cancer Aid)/ ; 464797012//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; DE 2360/6-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; P30 CA008748/CA/NCI NIH HHS/United States ; DJCLS 01 GvHD/2016//Jos&amp; Carreras Leuk&amp;mie-Stiftung (Deutsche Jos&amp; Carreras Leuk&amp;mie-Stiftung)/ ; 2021.040.1//Wilhelm Sander-Stiftung (Wilhelm Sander Foundation)/ ; 395357507//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 360372040//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BA 2851/6-1, 360372040//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 324392634, 395357507//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; DE 2360/1-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; R01-HL123340, R01-HL147584//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; }, mesh = {Humans ; *Bacteriophages/genetics ; Feces/microbiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Bacteria/genetics/metabolism ; Butyric Acid/metabolism ; }, abstract = {The microbiome is a predictor of clinical outcome in patients receiving allogeneic hematopoietic stem cell transplantation (allo-SCT). Microbiota-derived metabolites can modulate these outcomes. How bacteria, fungi and viruses contribute to the production of intestinal metabolites is still unclear. We combined amplicon sequencing, viral metagenomics and targeted metabolomics from stool samples of patients receiving allo-SCT (n = 78) and uncovered a microbiome signature of Lachnospiraceae and Oscillospiraceae and their associated bacteriophages, correlating with the production of immunomodulatory metabolites (IMMs). Moreover, we established the IMM risk index (IMM-RI), which was associated with improved survival and reduced relapse. A high abundance of short-chain fatty acid-biosynthesis pathways, specifically butyric acid via butyryl-coenzyme A (CoA):acetate CoA-transferase (BCoAT, which catalyzes EC 2.8.3.8) was detected in IMM-RI low-risk patients, and virome genome assembly identified two bacteriophages encoding BCoAT as an auxiliary metabolic gene. In conclusion, our study identifies a microbiome signature associated with protective IMMs and provides a rationale for considering metabolite-producing consortia and metabolite formulations as microbiome-based therapies.}, }
@article {pmid38170622, year = {2024}, author = {Huang, F and Cao, Y and Liang, J and Tang, R and Wu, S and Zhang, P and Chen, R}, title = {The influence of the gut microbiome on ovarian aging.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2295394}, pmid = {38170622}, issn = {1949-0984}, mesh = {Female ; Humans ; *Gastrointestinal Microbiome ; Ovary ; Aging ; *Microbiota ; }, abstract = {Ovarian aging occurs prior to the aging of other organ systems and acts as the pacemaker of the aging process of multiple organs. As life expectancy has increased, preventing ovarian aging has become an essential goal for promoting extended reproductive function and improving bone and genitourinary conditions related to ovarian aging in women. An improved understanding of ovarian aging may ultimately provide tools for the prediction and mitigation of this process. Recent studies have suggested a connection between ovarian aging and the gut microbiota, and alterations in the composition and functional profile of the gut microbiota have profound consequences on ovarian function. The interaction between the gut microbiota and the ovaries is bidirectional. In this review, we examine current knowledge on ovary-gut microbiota crosstalk and further discuss the potential role of gut microbiota in anti-aging interventions. Microbiota-based manipulation is an appealing approach that may offer new therapeutic strategies to delay or reverse ovarian aging.}, }
@article {pmid38169417, year = {2024}, author = {Cheng, S and Yu, J and Cui, M and Su, H and Cao, Y}, title = {Changes in the composition of the fecal metabolome and gut microbiota contribute to intervertebral disk degeneration in a rabbit model.}, journal = {Journal of orthopaedic surgery and research}, volume = {19}, number = {1}, pages = {6}, pmid = {38169417}, issn = {1749-799X}, mesh = {Animals ; Rabbits ; *Gastrointestinal Microbiome/genetics ; Dysbiosis/microbiology ; *Intervertebral Disc Degeneration ; Metabolome ; DNA, Ribosomal ; Tyrosine ; }, abstract = {PURPOSE: Lower back pain (LBP), mainly caused by intervertebral disk (IVD) degeneration (IDD), is widely prevalent worldwide and is a serious socioeconomic burden. Numerous factors may trigger this degenerative process, and microbial dysbiosis has recently been implicated as one of the likely causes. However, the exact relationship between IDD and the microbiome remains obscure. In this study, we investigated the gut microbiota composition and fecal metabolic phenotype and discussed the possible influences of microbiome dysbiosis on IDD.<br><br>METHODS: Fecal DNA was extracted from 16 fecal samples (eight rabbit models with IDD and eight sex- and age-matched healthy controls) and analyzed by high-throughput 16S rDNA sequencing. The fecal samples were also analyzed by liquid chromatography-mass spectrometry-based metabolomics. Multivariate analyses were conducted for the relationship between the omics data and IDD, linear discriminant analysis effect size was employed for biomarker discovery. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the differential metabolites. The potential correlation between differential gut microbiota and metabolites was then assessed.<br><br>RESULTS: The 16S rDNA sequencing results showed that the &#x3b2;-diversity of the gut microbiota was significantly different between the IDD and control groups, with distinct abundance levels of dominant genera. Moreover, 59 metabolites were significantly upregulated and 91 were downregulated in IDD rabbits versus the controls. The KEGG enrichment analysis revealed that the top pathways remarkably impacted by IDD were tyrosine metabolism, amino sugar and nucleotide sugar metabolism, benzoate degradation, ABC transporters, ascorbate and aldarate metabolism, pantothenate and CoA biosynthesis, and pyrimidine metabolism. The correlation analysis revealed that DL-tyrosine and N-acetylmuramic acid were associated with multiple differential bacterial genera, including Helicobacter and Vibrio, which may play important roles in the process of IVD degeneration.<br><br>CONCLUSION: Our findings revealed that IDD altered gut microbiota and fecal metabolites in a rabbit model. The correlation analysis of microbiota and metabolome provides a deeper understanding of IDD and its possible etiopathogenesis. These results also provide a direction and theoretical basis for the clinical application of fecal transplantation, probiotics, and other methods to regulate gut microbiota in the treatment of LBP caused by IDD.}, }
@article {pmid38168034, year = {2024}, author = {Zhu, L and Jian, X and Zhou, B and Liu, R and Muñoz, M and Sun, W and Xie, L and Chen, X and Peng, C and Maurer, M and Li, J}, title = {Gut microbiota facilitate chronic spontaneous urticaria.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {112}, pmid = {38168034}, issn = {2041-1723}, support = {81974476//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82173424//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82073458//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81830096//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Dysbiosis/microbiology ; *Dermatitis ; *Chronic Urticaria ; Inflammation ; *Gastrointestinal Microbiome ; Fatty Acids, Volatile/metabolism ; Humans ; Clostridiales ; Mice ; Lipopolysaccharides/pharmacology ; Animals ; }, abstract = {Chronic spontaneous urticaria (CSU) comes with gut dysbiosis, but its relevance remains elusive. Here we use metagenomics sequencing and short-chain fatty acids metabolomics and assess the effects of human CSU fecal microbial transplantation, Klebsiella pneumoniae, Roseburia hominis, and metabolites in vivo. CSU gut microbiota displays low diversity and short-chain fatty acids production, but high gut Klebsiella pneumoniae levels, negatively correlates with blood short-chain fatty acids levels and links to high disease activity. Blood lipopolysaccharide levels are elevated, link to rapid disease relapse, and high gut levels of conditional pathogenic bacteria. CSU microbiome transfer and Klebsiella pneumoniae transplantation facilitate IgE-mediated mast cell(MC)-driven skin inflammatory responses and increase intestinal permeability and blood lipopolysaccharide accumulation in recipient mice. Transplantation of Roseburia hominis and caproate administration protect recipient mice from MC-driven skin inflammation. Here, we show gut microbiome alterations, in CSU, may reduce short-chain fatty acids and increase lipopolysaccharide levels, respectively, and facilitate MC-driven skin inflammation.}, }
@article {pmid38164399, year = {2023}, author = {Shayya, NW and Bandick, R and Busmann, LV and Mousavi, S and Bereswill, S and Heimesaat, MM}, title = {Metabolomic signatures of intestinal colonization resistance against Campylobacter jejuni in mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1331114}, pmid = {38164399}, issn = {1664-302X}, abstract = {INTRODUCTION: Campylobacter jejuni stands out as one of the leading causes of bacterial enteritis. In contrast to humans, specific pathogen-free (SPF) laboratory mice display strict intestinal colonization resistance (CR) against C. jejuni, orchestrated by the specific murine intestinal microbiota, as shown by fecal microbiota transplantation (FMT) earlier.<br><br>METHODS: Murine infection models, comprising SPF, SAB, hma, and mma mice were employed. FMT and microbiota depletion were confirmed by culture and culture-independent analyses. Targeted metabolome analyses of fecal samples provided insights into the associated metabolomic signatures.<br><br>RESULTS: In comparison to hma mice, the murine intestinal microbiota of mma and SPF mice (with CR against C. jejuni) contained significantly elevated numbers of lactobacilli, and Mouse Intestinal Bacteroides, whereas numbers of enterobacteria, enterococci, and Clostridium coccoides group were reduced. Targeted metabolome analysis revealed that fecal samples from mice with CR contained increased levels of secondary bile acids and fatty acids with known antimicrobial activities, but reduced concentrations of amino acids essential for C. jejuni growth as compared to control animals without CR.<br><br>DISCUSSION: The findings highlight the role of microbiota-mediated nutrient competition and antibacterial activities of intestinal metabolites in driving murine CR against C. jejuni. The study underscores the complex dynamics of host-microbiota-pathogen interactions and sets the stage for further investigations into the mechanisms driving CR against enteric infections.}, }
@article {pmid38163440, year = {2024}, author = {Lu, X and Yang, R and Chen, Y and Chen, D}, title = {Evaluating the therapeutic efficacy of NAD supplementation in management of metabolic dysfunction-associated steatotic liver disease: Key considerations.}, journal = {Clinical and molecular hepatology}, volume = {30}, number = {3}, pages = {582-584}, pmid = {38163440}, issn = {2287-285X}, support = {2022-QY-216//Qinghai Province Key Research and Development and Transformation Plan Specific fund of Science and Technology Assistance to Qinghai/ ; }, mesh = {Humans ; *NAD/metabolism ; Dietary Supplements ; Non-alcoholic Fatty Liver Disease/drug therapy/pathology/complications/diagnosis/metabolism ; Fatty Liver/complications/diagnosis ; }, }
@article {pmid38162858, year = {2023}, author = {Toshida, K and Itoh, S and Kosai-Fujimoto, Y and Ishikawa, T and Nakayama, Y and Tsutsui, Y and Iseda, N and Izumi, T and Bekki, Y and Yoshiya, S and Toshima, T and Nakamuta, M and Yoshizumi, T}, title = {Association of gut microbiota with portal vein pressure in patients with liver cirrhosis undergoing living donor liver transplantation.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {7}, number = {12}, pages = {982-989}, pmid = {38162858}, issn = {2397-9070}, abstract = {BACKGROUND AND AIM: Many recent studies have shown a relationship between various systemic diseases and the gut microbiota (GM), with the gut-liver axis receiving particular attention. In contrast, no report has comprehensively shown the effects of GM on the pathophysiology of patients undergoing living donor liver transplantation (LDLT).<br><br>METHOD: We enrolled 16 recipients who underwent LDLT for liver cirrhosis, and 17 donors constituted the reference group. We examined the differences in GM between recipients and donors. We also examined the relationships between GM, short-chain fatty acids, and portal vein pressure (PVP) in recipients.<br><br>RESULTS: There was no significant difference in alpha-diversity between the recipients and donors, but there was variation in beta-diversity among the recipients. The abundance of the phylum Bacteroidetes was significantly higher in recipients than in donors (P&#x2009;=&#x2009;0.016), and it was positively correlated with PVP (r&#x2009;=&#x2009;0.511, P&#x2009;=&#x2009;0.043). Propionic acid, which is a component of short-chain fatty acids, was positively correlated with PVP (r&#x2009;=&#x2009;0.544, P&#x2009;=&#x2009;0.0295), the phylum Bacteroidetes (r&#x2009;=&#x2009;0.677, P&#x2009;=&#x2009;0.004), and total bilirubin concentration (r&#x2009;=&#x2009;0.501, P&#x2009;=&#x2009;0.048). Propionic acid was negatively correlated with serum albumin concentration (r&#x2009;=&#x2009;-0.482, P&#x2009;=&#x2009;0.043).<br><br>CONCLUSION: Our findings suggest relationships between fecal Bacteroidetes levels, propionic acid concentrations, and PVP in patients with liver cirrhosis undergoing LDLT.}, }
@article {pmid38158466, year = {2024}, author = {Terra, DAA and de Oliveira Carvalho, RD and da Silva, TF and Dos Santos Freitas, A and Góes-Neto, A and Amarante, VS and Azevedo, V and Vilela, EG and Coelho, LGV and Silva, ROS}, title = {Bacterial microbiome changes after fecal transplantation for recurrent Clostridioides difficile infection in the Brazilian center.}, journal = {Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]}, volume = {55}, number = {1}, pages = {719-725}, pmid = {38158466}, issn = {1678-4405}, support = {FAPEMIG RED-00132-16//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de Minas Gerais/ ; }, mesh = {Humans ; Fecal Microbiota Transplantation ; Brazil ; Feces/microbiology ; *Clostridioides difficile ; Treatment Outcome ; *Clostridium Infections/microbiology ; *Microbiota ; Bacteria ; }, abstract = {Clostridioides difficile infection (CDI) poses a significant global health threat owing to its substantial morbidity and associated healthcare costs. A key challenge in controlling CDI is the risk of multiple recurrences, which can affect up to 30% of patients. In such instances, fecal microbiota transplantation (FMT) is increasingly recognized as the optimal treatment. However, few related studies have been conducted in developing countries, and the microbiota composition of Brazilian patients and its dynamic modification post-FMT remain largely unexplored. This study aimed to evaluate the changes in the bacterial gut microbiome in Brazilian patients with recurrent CDI post-FMT. Ten patients underwent FMT, and the primary and overall CDI resolution rates were 80% and 90% after the first and second FMT, respectively. FMT was associated with an early increase in Shannon's diversity, evident as soon as 1 week post-FMT and persisting for at least 25 days post-treatment. Post-treatment, the abundance of Firmicutes increased and that of Proteobacteria decreased. Specifically, the abundance of the genera Ruminococcus, Faecalibacterium, Lachnospira, and Roseburia of the Firmicutes phylum was significantly higher 1 week post-transplantation, with Ruminococcus and Faecalibacterium remaining enriched 25 days post-transplantation. This study is the first of its kind in Brazil to evaluate the microbiota of a donor and patients undergoing FMT. Our findings suggest that FMT can induce remarkable changes in the gut microbiota, characterized by an early and sustained increase in diversity lasting at least 25 days. FMT also promotes enrichment of genera such as Ruminococcus spp., Faecalibacterium spp., and Roseburia spp., essential for therapeutic success.}, }
@article {pmid38157106, year = {2024}, author = {Chen, S and Huang, L and Liu, B and Duan, H and Li, Z and Liu, Y and Li, H and Fu, X and Lin, J and Xu, Y and Liu, L and Wan, D and Yin, Y and Xie, L}, title = {Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging.}, journal = {Science China. Life sciences}, volume = {67}, number = {4}, pages = {745-764}, pmid = {38157106}, issn = {1869-1889}, mesh = {Mice ; Animals ; *Butyrates ; *Dysbiosis ; RNA, Ribosomal, 16S/genetics ; Aging ; Homeostasis ; }, abstract = {The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions, such as developing and preserving the skeletal muscle system. However, the interplay between gut microbiota/metabolites and the regulation of satellite cell (SC) homeostasis, particularly during aging, remains elusive. We propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development, regeneration, and aging process. Our investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice, leads to the activation of SCs or a significant reduction in the total number. Furthermore, employing multi-omics (e.g., RNA-seq, 16S rRNA gene sequencing, and metabolomics) and bioinformatic analysis, we demonstrate that the reduced butyrate levels, alongside the gut microbial dysbiosis, could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle aging. Meanwhile, butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota, potentially by inhibiting the proliferation and differentiation of SCs/myoblasts. The butyrate effect is likely facilitated through the monocarboxylate transporter 1 (Mct1), a lactate transporter enriched on membranes of SCs and myoblasts. As a result, butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle aging. Our findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.}, }
@article {pmid38156008, year = {2023}, author = {He, KY and Lei, XY and Zhang, L and Wu, DH and Li, JQ and Lu, LY and Laila, UE and Cui, CY and Xu, ZX and Jian, YP}, title = {Development and management of gastrointestinal symptoms in long-term COVID-19.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1278479}, pmid = {38156008}, issn = {1664-302X}, abstract = {BACKGROUND: Emerging evidence reveals that SARS-CoV-2 possesses the capability to disrupt the gastrointestinal (GI) homeostasis, resulting in the long-term symptoms such as loss of appetite, diarrhea, gastroesophageal reflux, and nausea. In the current review, we summarized recent reports regarding the long-term effects of COVID-19 (long COVID) on the gastrointestine.<br><br>OBJECTIVE: To provide a narrative review of abundant clinical evidence regarding the development and management of long-term GI symptoms in COVID-19 patients.<br><br>RESULTS: Long-term persistent digestive symptoms are exhibited in a majority of long-COVID patients. SARS-CoV-2 infection of intestinal epithelial cells, cytokine storm, gut dysbiosis, therapeutic drugs, psychological factors and exacerbation of primary underlying diseases lead to long-term GI symptoms in COVID-19 patients. Interventions like probiotics, prebiotics, fecal microbiota transplantation, and antibiotics are proved to be beneficial in preserving intestinal microecological homeostasis and alleviating GI symptoms.<br><br>CONCLUSION: Timely diagnosis and treatment of GI symptoms in long-COVID patients hold great significance as they may contribute to the mitigation of severe conditions and ultimately lead to the improvement of outcomes of the patients.}, }
@article {pmid38155743, year = {2023}, author = {Sun, X and Zhou, X and He, W and Sun, W and Xu, Z}, title = {Co-Housing and Fecal Microbiota Transplantation: Technical Support for TCM Herbal Treatment of Extra-Intestinal Diseases Based on Gut Microbial Ecosystem Remodeling.}, journal = {Drug design, development and therapy}, volume = {17}, number = {}, pages = {3803-3831}, pmid = {38155743}, issn = {1177-8881}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Housing ; *Intestinal Diseases/drug therapy ; }, abstract = {Dysregulation of the gut microbial ecosystem (GME) (eg, alterations in the gut microbiota, gut-derived metabolites, and gut barrier) may contribute to the onset and progression of extra-intestinal diseases. Previous studies have found that Traditional Chinese Medicine herbs (TCMs) play an important role in manipulating the GME, but a prominent obstacle in current TCM research is the causal relationship between GME and disease amelioration. Encouragingly, co-housing and fecal microbiota transplantation (FMT) provide evidence-based support for TCMs to treat extra-intestinal diseases by targeting GME. In this review, we documented the principles, operational procedures, applications and limitations of the key technologies (ie, co-housing and FMT); furthermore, we provided evidence that TCM works through the GME, especially the gut microbiota (eg, SCFA- and BSH-producing bacteria), the gut-derived metabolites (eg, IS, pCS, and SCFAs), and intestinal barrier to alleviate extra-intestinal diseases. This will be beneficial in constructing microecological pathways for TCM treatment of extra-intestinal diseases in the future.}, }
@article {pmid38154268, year = {2024}, author = {Dong, P and Wang, H and Li, Y and Yu, J and Liu, X and Wang, Y and Dai, L and Wang, S}, title = {Active peptides from Eupolyphaga sinensis walker attenuates experimental hyperlipidemia by regulating the gut microbiota and biomarkers in rats with dyslipidemia.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {170}, number = {}, pages = {116064}, doi = {10.1016/j.biopha.2023.116064}, pmid = {38154268}, issn = {1950-6007}, mesh = {Rats ; Animals ; *Hyperlipidemias/metabolism ; *Gastrointestinal Microbiome ; Zebrafish ; Diet, High-Fat/adverse effects ; Biomarkers ; Lactobacillus ; Bacteria ; gamma-Aminobutyric Acid/pharmacology ; *Hominidae ; }, abstract = {Eupolyphaga sinensis Walker (ESW) is a traditional Chinese medicine formulation used to treat hyperlipidemia. However, the hypolipidemic effect of the active peptides from E. sinensis Walker (APE) is incompletely understood. We studied the hypolipidemic effect of APE and explored the impact of APE on the gut microbiota (GM) in rats suffering from hyperlipidemia. APE was prepared by enzymatic digestion, and its structure was characterized using various methods. The anti-hyperlipidemic activity of APE was assessed using a high-fat diet (HFD)-induced model in zebrafish and rats. In rats, HFD administration caused abnormalities of lipid metabolism and disturbances of the GM and amino acid (AA) profile in plasma. The abundance of bacteria of the phyla Firmicutes and Bacteroides was increased significantly (p < 0.05), and the relative abundance of Lactobacillus species and Clostridium species was decreased significantly (p < 0.05). HFD therapy affected the levels of 12 AAs in vivo: 10 AAs showed increased levels and two AAs had decreased levels (p < 0.05). Similar results were demonstrated in an experiment on fecal microbiota transplantation. APE treatment dose-dependently decreased lipid factors and liver damage (p < 0.05). Sequencing of the 16 S rRNA gene indicated that APE improved the intestinal-flora structure of rats with HL markedly, and increased the relative abundance of Lactobacillus species and Clostridium species. Metabolomics analysis indicated that APE could alter the levels of 10 AAs affected by HFD consumption. Spearman correlation analysis revealed that gamma-aminobutyric acid (GABA) could be a crucial metabolite, and Lactobacillus species and Clostridium species might be important bacteria for the action of APE against hyperlipidemia. We speculate that APE exhibited an anti-hyperlipidemic effect by regulating GABA synthesis in the presence of Lactobacillus species and Clostridium species.}, }
@article {pmid38153838, year = {2024}, author = {Yang, CJ and Chang, HC and Sung, PC and Ge, MC and Tang, HY and Cheng, ML and Cheng, HT and Chou, HH and Lin, CY and Lin, WR and Lee, YS and Hsieh, SY}, title = {Oral fecal transplantation enriches Lachnospiraceae and butyrate to mitigate acute liver injury.}, journal = {Cell reports}, volume = {43}, number = {1}, pages = {113591}, doi = {10.1016/j.celrep.2023.113591}, pmid = {38153838}, issn = {2211-1247}, mesh = {Humans ; Animals ; Mice ; *Fecal Microbiota Transplantation ; *Butyrates ; Feces ; Liver ; }, abstract = {While fecal microbiota transplantation (FMT) shows promise in treating human diseases, oral capsule FMT is more accepted and accessible to patients. However, microbe selection in the upper gastrointestinal tract (UGIT) through oral administration remains unclear. Here, we demonstrate that short-term oral fecal gavage (OFG) alleviates acetaminophen-induced acute liver injury (AILI) in mice, regardless of the divergent effects of commensal gut microbes. Pasteurized fecal gavage yields similar therapeutic effects. OFG enriches gut Lachnospiraceae and butyrate compared to donor feces. Butyrate mitigates AILI-induced ferroptosis via AMPK-ULK1-p62 signaling to simultaneously induce mitophagy and Nrf2 antioxidant responses. Combined N-acetylcysteine and butyrate administration significantly improves AILI mouse survival rates. These observations indicate the significance of the UGIT in modulating the implanted fecal microbes through oral administration and its potential biological and clinical impacts. Our findings also highlight a possible strategy for applying microbial metabolites to treat acute liver injury.}, }
@article {pmid38153260, year = {2024}, author = {Cross, TL and Simpson, AMR and Lin, CY and Hottmann, NM and Bhatt, AP and Pellock, SJ and Nelson, ER and Loman, BR and Wallig, MA and Vivas, EI and Suchodolski, J and Redinbo, MR and Rey, FE and Swanson, KS}, title = {Gut microbiome responds to alteration in female sex hormone status and exacerbates metabolic dysfunction.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2295429}, pmid = {38153260}, issn = {1949-0984}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R01 HL144651/HL/NHLBI NIH HHS/United States ; R01 HL148577/HL/NHLBI NIH HHS/United States ; T32 HL007936/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Female ; Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Obesity/metabolism ; Liver/metabolism ; Diet, High-Fat/adverse effects ; Inflammation/metabolism ; Gonadal Steroid Hormones/metabolism ; Mice, Inbred C57BL ; }, abstract = {Women are at significantly greater risk of metabolic dysfunction after menopause, which subsequently leads to numerous chronic illnesses. The gut microbiome is associated with obesity and metabolic dysfunction, but its interaction with female sex hormone status and the resulting impact on host metabolism remains unclear. Herein, we characterized inflammatory and metabolic phenotypes as well as the gut microbiome associated with ovariectomy and high-fat diet feeding, compared to gonadal intact and low-fat diet controls. We then performed fecal microbiota transplantation (FMT) using gnotobiotic mice to identify the impact of ovariectomy-associated gut microbiome on inflammatory and metabolic outcomes. We demonstrated that ovariectomy led to greater gastrointestinal permeability and inflammation of the gut and metabolic organs, and that a high-fat diet exacerbated these phenotypes. Ovariectomy also led to alteration of the gut microbiome, including greater fecal β-glucuronidase activity. However, differential changes in the gut microbiome only occurred when fed a low-fat diet, not the high-fat diet. Gnotobiotic mice that received the gut microbiome from ovariectomized mice fed the low-fat diet had greater weight gain and hepatic gene expression related to metabolic dysfunction and inflammation than those that received intact sham control-associated microbiome. These results indicate that the gut microbiome responds to alterations in female sex hormone status and contributes to metabolic dysfunction. Identifying and developing gut microbiome-targeted modulators to regulate sex hormones may be useful therapeutically in remediating menopause-related diseases.}, }
@article {pmid38153222, year = {2024}, author = {Feuerstadt, P and LaPlante, KL}, title = {Efficacy and Practical Implementation of Fecal Microbiota Spores, Live-BRPK: A Novel Approach for Preventing Recurrent Clostridioides difficile Infection.}, journal = {The American journal of gastroenterology}, volume = {119}, number = {1S}, pages = {S22-S26}, doi = {10.14309/ajg.0000000000002582}, pmid = {38153222}, issn = {1572-0241}, mesh = {Humans ; Spores, Bacterial ; *Clostridium Infections/prevention &amp; control/drug therapy ; *Clostridioides difficile ; *Microbiota ; Fecal Microbiota Transplantation ; Recurrence ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use ; }, }
@article {pmid38153221, year = {2024}, author = {Oneto, C and Khanna, S}, title = {Prescription Microbiome Therapeutic for Recurrent Clostridioides difficile Infection: Fecal Microbiota Live-jslm.}, journal = {The American journal of gastroenterology}, volume = {119}, number = {1S}, pages = {S16-S21}, doi = {10.14309/ajg.0000000000002577}, pmid = {38153221}, issn = {1572-0241}, mesh = {Humans ; *Clostridium Infections/drug therapy ; *Microbiota ; Fecal Microbiota Transplantation ; Recurrence ; Treatment Outcome ; }, }
@article {pmid38151280, year = {2023}, author = {Hanssen, HM and Fjellstad, MS and Skjevling, L and Johnsen, PH and Kulseng, B and Goll, R and Almå, KH and Valle, PC}, title = {Randomised, placebo-controlled, double-blinded trial of fecal microbiota transplantation in severe obesity: a study protocol.}, journal = {BMJ open}, volume = {13}, number = {12}, pages = {e073242}, pmid = {38151280}, issn = {2044-6055}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Obesity, Morbid/therapy/etiology ; Obesity/therapy/etiology ; Double-Blind Method ; Weight Loss ; Treatment Outcome ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Obesity is one of the main threats to public health in western countries and increases the risk of several diseases, overall morbidity and mortality. Sustained weight loss will reduce risk factors and improve several obesity comorbidities. Options are conservative treatment such as lifestyle changes, bariatric surgery or medications. Conservative treatment has a low success rate, and bariatric surgery is typically not reversible, with the risk of complications and recurrences. Treatment of obesity with medications has in recent years shown great promise, but the side effects are many, and the long-term effect is unknown. There is also a need for an option for patients where surgery has contraindications and conservative follow-up does not succeed.The research on obesity and gut microbiota has yielded promising results regarding weight reduction and metabolic health, but more research is needed to better understand the relationship between gut microbiota and severe obesity. This study could show proof of concept that gut microbiota from a lean donor could, in addition to lifestyle intervention, contribute to weight reduction in people suffering from severe obesity.<br><br>METHOD AND ANALYSIS: This study aims to investigate if a fecal microbiota transplantation (FMT) from a lean donor leads to weight reduction in participants suffering from severe obesity. The study is a single-centre, double-blinded, placebo-controlled, parallel-group study with 60 participants. Participants will be randomised 1:1 for FMT from a lean donor or placebo. FMT or placebo will be delivered once by enema.We will include participants from the outpatient clinic for severe obesity, at the Medical Department, University Hospital of North Norway, Harstad, by invitation only. The study has a follow-up period of 12 months, with study visits of 3, 6 and 12 months post FMT. The primary endpoint is a weight reduction of &#x2265;10%, 12 months after intervention.The results of the study will be published in open access journals. At the end of the study, the participants will receive information on which treatment group they belong to.<br><br>ETHICS AND DISSEMINATION: The Regional Ethical Committee in North Norway (REK) approved the study protocol (2017/1655/REK Nord). We plan to present the results from the study at (inter)national conferences and publish in open-access general peer-reviewed journals. The enema method for FMT administration used in this study was developed by our study team.<br><br>TRIAL REGISTRATION NUMBER: NCT03273855.}, }
@article {pmid38150616, year = {2024}, author = {Huang, X and He, X and Chen, X and Li, Y}, title = {Fecal Microbiota Transplantation Alleviates Severe PD-1 Inhibitor-Associated Colitis Caused by Neoadjuvant Therapy for Esophageal Cancer: A Case Report.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {47}, number = {5}, pages = {331-337}, pmid = {38150616}, issn = {1538-9766}, mesh = {Humans ; Male ; Middle Aged ; *Fecal Microbiota Transplantation ; *Neoadjuvant Therapy ; *Esophageal Neoplasms/therapy ; Colitis/therapy ; Immune Checkpoint Inhibitors/adverse effects/therapeutic use ; }, abstract = {Surgical resection is the preferred treatment for early-stage esophageal cancer. But most patients with esophageal cancer are diagnosed at advanced stages, making them ineligible for surgery. Therefore, preoperative neoadjuvant therapy has been introduced to help them meet surgical requirements. However, this therapy has been associated with serious complications, such as diarrhea, preventing patients from surgery. During neoadjuvant therapy combined with chemoradiotherapy, a 58-year-old male patient with esophageal cancer was diagnosed with severe immune-related colitis, which seriously affected both cancer treatment and the patient's quality of life. Despite conventional antidiarrheal therapy, the patient remained refractory to treatment. However, after undergoing fecal microbiota transplantation, the frequency of diarrhea was significantly reduced. During e-colonoscopy, no significant ulcers were found in the sigmoid colon. Additionally, successful radical resection of esophageal cancer was performed, resulting in a favorable outcome for the patient. Regular follow-up appointments were scheduled to monitor the patient's progress. Fecal microbiota transplantation effectively relieved severe immune-related diarrhea in a patient undergoing neoadjuvant immunotherapy and chemoradiotherapy for esophageal cancer. This successful treatment ultimately enabled the patient to meet the surgical requirements for radical esophagectomy.}, }
@article {pmid38148326, year = {2023}, author = {Song, Y and Lau, HC and Zhang, X and Yu, J}, title = {Bile acids, gut microbiota, and therapeutic insights in hepatocellular carcinoma.}, journal = {Cancer biology &amp; medicine}, volume = {21}, number = {2}, pages = {144-162}, pmid = {38148326}, issn = {2095-3941}, support = {2020J01122587//Fujian Provincial Natural Science Foundation project/ ; 82103355//National Natural Science Foundation of China/ ; 82102255//National Natural Science Foundation of China/ ; 82222901//National Natural Science Foundation of China/ ; T12-703/19-R//RGC Theme-based Research Scheme/ ; 14117422//Research grants Council-General Research Fund/ ; 14117123//Research grants Council-General Research Fund/ ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy ; Bile Acids and Salts ; *Gastrointestinal Microbiome ; *Liver Neoplasms/therapy ; }, abstract = {Hepatocellular carcinoma (HCC) is a prevalent and aggressive liver malignancy. The interplay between bile acids (BAs) and the gut microbiota has emerged as a critical factor in HCC development and progression. Under normal conditions, BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs. The gut microbiota plays a critical role in BA metabolism, and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis. Of note, dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis, thereby leading to liver inflammation and fibrosis, and ultimately contributing to HCC development. Therefore, understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis. In this review, we comprehensively explore the roles and functions of BA metabolism, with a focus on the interactions between BAs and gut microorganisms in HCC. Additionally, therapeutic strategies targeting BA metabolism and the gut microbiota are discussed, including the use of BA agonists/antagonists, probiotic/prebiotic and dietary interventions, fecal microbiota transplantation, and engineered bacteria. In summary, understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.}, }
@article {pmid38147728, year = {2024}, author = {Feng, H and Xiong, J and Liang, S and Wang, Y and Zhu, Y and Hou, Q and Yang, X and Yang, X}, title = {Fecal virus transplantation has more moderate effect than fecal microbiota transplantation on changing gut microbial structure in broiler chickens.}, journal = {Poultry science}, volume = {103}, number = {2}, pages = {103282}, pmid = {38147728}, issn = {1525-3171}, mesh = {Animals ; *Fecal Microbiota Transplantation/veterinary ; Chickens/microbiology ; *Gastrointestinal Microbiome ; Occludin ; Immunoglobulin A, Secretory ; }, abstract = {Growing evidence of fecal microbiota transplantation (FMT) and fecal virus transplantation (FVT) provides a possibility to regulate animal health, whereas little is known about the impact of the 2 methods. This study aimed to investigate the effects of gut microbes on jejunal function in healthy broiler chickens, with the objective of establishing a theoretical basis for the application of FMT and FVT. Cecal feces from 28-day-old AA broilers were collected to prepare gavage juice for FMT and FVT. FMT for Group FM, FVT for group FV and PBS gavage for group CON, continuously treated for 6 days start at 5-day-old chicks. Samples were collected at d 11 and d 21. The results showed that the treatment d 2 and the overall fecal score in treatment groups were significantly lower than CON group (P < 0.05). The jejunum morphology showed that FMT increased crypt depth, decreased villus height, V/C (P < 0.05) and FVT increased villus height (P < 0.05) at d 11. At d 21, villus height and crypt depth significantly higher (P < 0.05) in group FM and group FV. The expression of Claudin1, Occludin, ZO2, and Muc2 in the FV group was significantly increased (P < 0.05) at 11-day-old. FMT increased the secretion of sIgA at 11-day-old, and this influence lasted up to 21-day-old (P < 0.05). At 11-day-old, the expression of b[0+]AT of basic amino acid transport carrier and chymotrypsin activity (P < 0.05) had a significant correlation. At 21 d of age, FVT significantly increased the expression of PepT1 and SGLT1 (P < 0.05). At 11-day-old, FM group showed significantly higher faith pd index (P = 0.004) and Shannon index (P = 0.037), and separated from FV and CON according to PCoA. Among differentiating bacteria, Bacteroides significantly enriched (P < 0.05) in group FM, which positively correlated with the expression of ZO2, Muc2, Occludin, and Claudin1; R_Ruminococcus, L_Ruminococcus, Butyricicoccuss significantly enriched (P < 0.05) in group CON, which significantly higher than processing groups, R_Ruminococcus and L_Ruminococcus negatively correlated with the expression of Occludin (P < 0.05), and R_Ruminococcus, Butyricicoccus negatively correlated with the expression of Claudin1 (P < 0.05). At 21-day-old, PCoA based on Bray-Curtis shows that microbes taxa of 3 groups are isolated with each other and treatment groups were significant different with CON group based on Unweighted UniFrac and weighted UniFrac. The expression of PepT1 was significantly negatively (P < 0.05) correlated with Ruminococcus, and the expression of sIgA was significantly negatively (P < 0.05) correlated with Parabacteroides. In conclusion, FMT regulated intestinal flora rapidly, while it had little effect on intestinal function and a higher potential damaging risk on jejunal. FVT regulated intestinal flora structure softer, improved tight junction expression, but the mechanism of action needs further exploration.}, }
@article {pmid38147649, year = {2024}, author = {Ritz, NL and Brocka, M and Butler, MI and Cowan, CSM and Barrera-Bugueño, C and Turkington, CJR and Draper, LA and Bastiaanssen, TFS and Turpin, V and Morales, L and Campos, D and Gheorghe, CE and Ratsika, A and Sharma, V and Golubeva, AV and Aburto, MR and Shkoporov, AN and Moloney, GM and Hill, C and Clarke, G and Slattery, DA and Dinan, TG and Cryan, JF}, title = {Social anxiety disorder-associated gut microbiota increases social fear.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {1}, pages = {e2308706120}, pmid = {38147649}, issn = {1091-6490}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Animals ; Mice ; *Phobia, Social ; *Gastrointestinal Microbiome/physiology ; Oxytocin ; RNA, Ribosomal, 16S/genetics ; Fear ; Anxiety/psychology ; }, abstract = {Social anxiety disorder (SAD) is a crippling psychiatric disorder characterized by intense fear or anxiety in social situations and their avoidance. However, the underlying biology of SAD is unclear and better treatments are needed. Recently, the gut microbiota has emerged as a key regulator of both brain and behaviour, especially those related to social function. Moreover, increasing data supports a role for immune function and oxytocin signalling in social responses. To investigate whether the gut microbiota plays a causal role in modulating behaviours relevant to SAD, we transplanted the microbiota from SAD patients, which was identified by 16S rRNA sequencing to be of a differential composition compared to healthy controls, to mice. Although the mice that received the SAD microbiota had normal behaviours across a battery of tests designed to assess depression and general anxiety-like behaviours, they had a specific heightened sensitivity to social fear, a model of SAD. This distinct heightened social fear response was coupled with changes in central and peripheral immune function and oxytocin expression in the bed nucleus of the stria terminalis. This work demonstrates an interkingdom basis for social fear responses and posits the microbiome as a potential therapeutic target for SAD.}, }
@article {pmid38143595, year = {2023}, author = {Kamal, FD and Dagar, M and Reza, T and Karim Mandokhail, A and Bakht, D and Shahzad, MW and Silloca-Cabana, EO and Mohsin, SN and Chilla, SP and Bokhari, SFH}, title = {Beyond Diet and Exercise: The Impact of Gut Microbiota on Control of Obesity.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e49339}, pmid = {38143595}, issn = {2168-8184}, abstract = {Obesity, a widespread health concern characterized by the excessive accumulation of body fat, is a complex condition influenced by genetics, environment, and social determinants. Recent research has increasingly focused on the role of gut microbiota in obesity, highlighting its pivotal involvement in various metabolic processes. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, interacts with the host in a myriad of ways, impacting energy metabolism, appetite regulation, inflammation, and the gut-brain axis. Dietary choices significantly shape the gut microbiota, with diets high in fat and carbohydrates promoting the growth of harmful bacteria while reducing beneficial microbes. Lifestyle factors, like physical activity and smoking, also influence gut microbiota composition. Antibiotics and medications can disrupt microbial diversity, potentially contributing to obesity. Early-life experiences, including maternal obesity during pregnancy, play a vital role in the developmental origins of obesity. Therapeutic interventions targeting the gut microbiota, including prebiotics, probiotics, fecal microbiota transplantation, bacterial consortium therapy, and precision nutrition, offer promising avenues for reshaping the gut microbiota and positively influencing weight regulation and metabolic health. Clinical applications of microbiota-based therapies are on the horizon, with potential implications for personalized treatments and condition-based interventions. Emerging technologies, such as next-generation sequencing and advanced bioinformatics, empower researchers to identify specific target species for microbiota-based therapeutics, opening new possibilities in healthcare. Despite the promising outlook, microbiota-based therapies face challenges related to microbial selection, safety, and regulatory issues. However, with ongoing research and advances in the field, these challenges can be addressed to unlock the full potential of microbiota-based interventions.}, }
@article {pmid38138246, year = {2023}, author = {Ilie, OD and Duta, R and Nita, IB and Dobrin, I and Gurzu, IL and Girleanu, I and Huiban, L and Muzica, C and Ciobica, A and Popescu, R and Cianga, P and Stanciu, C and Cimpoesu, D and Trifan, A}, title = {A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {12}, pages = {}, pmid = {38138246}, issn = {1648-9144}, mesh = {Humans ; *Hepatic Encephalopathy/therapy ; Randomized Controlled Trials as Topic ; Lactulose/therapeutic use ; Liver Cirrhosis/complications/drug therapy ; *Probiotics/therapeutic use ; }, abstract = {Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.}, }
@article {pmid38138045, year = {2023}, author = {Bosch, B and Hartikainen, A and Ronkainen, A and Scheperjans, F and Arkkila, P and Satokari, R}, title = {Development of a Protocol for Anaerobic Preparation and Banking of Fecal Microbiota Transplantation Material: Evaluation of Bacterial Richness in the Cultivated Fraction.}, journal = {Microorganisms}, volume = {11}, number = {12}, pages = {}, pmid = {38138045}, issn = {2076-2607}, support = {6600A-C1012//Finnish National Agency for Education/ ; 323156//Academy of Finland/ ; TYH2019204//The Hospital District of Helsinki and Uusimaa/ ; }, abstract = {Fecal microbiota transplantation (FMT) has shown highly variable results in indications beyond recurrent Clostridioides difficile infection. Microbiota dysbiosis in many diseases is characterized by the depletion of strictly anaerobic bacteria, which may be crucial for FMT efficacy. We developed a protocol to ensure anaerobic conditions during the entire transplant preparation and banking process, from material collection to administration. The protocol necessitates an anaerobic cabinet, i.e., a non-standard laboratory equipment. We analyzed the population of viable anaerobes by combining cultivation and 16S rRNA gene profiling during the transplant preparation, and after 4, 8, and 12 months of anaerobic or aerobic storage at -80 °C, 78% of fecal species were captured via cultivation. Our findings suggest that strictly anaerobic transplant preparation and storage may preserve species richness better than oxic conditions, but the overall difference was not significant. However, specific anaerobes such as Neglecta and Anaerotruncus were affected by the oxygen exposure. A storage time of up to 12 months did not affect the presence of cultivated taxa. Noteworthy, our analysis focused on the richness of cultivated anaerobes rather than their abundance, which may have been affected. The benefits of the developed anaerobic protocol in FMT for specific indications remain to be demonstrated in clinical trials.}, }
@article {pmid38137998, year = {2023}, author = {Li, M and Yang, H and Shao, C and Liu, Y and Wen, S and Tang, L}, title = {Application of Dominant Gut Microbiota Promises to Replace Fecal Microbiota Transplantation as a New Treatment for Alzheimer's Disease.}, journal = {Microorganisms}, volume = {11}, number = {12}, pages = {}, pmid = {38137998}, issn = {2076-2607}, abstract = {Several studies have confirmed that the pathophysiological progression of Alzheimer's disease (AD) is closely related to changes in the intestinal microbiota; thus, modifying the intestinal microbiota has emerged as a new way to treat AD. Effective interventions for gut microbiota include the application of probiotics and other measures such as fecal microbiota transplantation (FMT). However, the application of probiotics ignores that the intestine is a complete microecosystem with competition among microorganisms. FMT also has issues when applied to patient treatment. In a previous study, we found that eight species of bacteria that are isolated with high frequency in the normal intestinal microbiota (i.e., intestinal dominant microbiota) have biological activities consistent with the effects of FMT. In this article, we confirmed that the treatment of intestinal dominant microbiota significantly restored intestinal microbiota abundance and composition to normal levels in APP/PS1 mice; downregulated brain tissue pro-inflammatory cytokines (IL-1β and IL-6) and amyloid precursor protein (APP) and β-site APP cleavage enzyme 1 (BACE1) expression levels; and reduced the area of Aβ plaque deposition in the brain hippocampus. Our study provides a new therapeutic concept for the treatment of AD, adjusting the intestinal microecological balance through dominant intestinal microbiota may be an alternative to FMT.}, }
@article {pmid38137984, year = {2023}, author = {Laeeq, T and Vongsavath, T and Tun, KM and Hong, AS}, title = {The Potential Role of Fecal Microbiota Transplant in the Reversal or Stabilization of Multiple Sclerosis Symptoms: A Literature Review on Efficacy and Safety.}, journal = {Microorganisms}, volume = {11}, number = {12}, pages = {}, pmid = {38137984}, issn = {2076-2607}, abstract = {Multiple sclerosis (MS) affects millions of people worldwide, and recent data have identified the potential role of the gut microbiome in inducing autoimmunity in MS patients. To investigate the potential of fecal microbiota transplant (FMT) as a treatment option for MS, we conducted a comprehensive literature search (PubMed/Medline, Embase, Web of Science, Scopus, and Cochrane) and identified five studies that involved 15 adult MS patients who received FMT for gastrointestinal symptoms. The primary outcome of this review was to assess the effect of FMT in reversing and improving motor symptoms in MS patients, while the secondary outcome was to evaluate the safety of FMT in this patient population. Our findings suggest that all 15 patients who received FMT experienced improved and reversed neurological symptoms secondary to MS. This improvement was sustained even in follow-up years, with no adverse effects observed. These results indicate that FMT may hold promise as a treatment option for MS, although further research is necessary to confirm these findings.}, }
@article {pmid38137770, year = {2023}, author = {Tikunov, AY and Fedorets, VA and Shrainer, EV and Morozov, VV and Bystrova, VI and Tikunova, NV}, title = {Intestinal Microbiome Changes and Clinical Outcomes of Patients with Ulcerative Colitis after Fecal Microbiota Transplantation.}, journal = {Journal of clinical medicine}, volume = {12}, number = {24}, pages = {}, pmid = {38137770}, issn = {2077-0383}, support = {21-14-00360//Russian Science Foundation/ ; }, abstract = {BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic inflammatory disease that affects many people. One of the possible ways to treat UC is fecal microbiota transplantation (FMT). In this study, changes in the intestinal microbiome and clinical outcomes of 20 patients with UC after FMT were estimated.<br><br>METHODS: FMT enemas were administrated ten times, once a day, and fecal microbiota from three donors was used for each enema. The clinical outcomes were assessed after eight weeks and then via a patient survey. The 16S rRNA profiles of the gut microbiota were compared between three samplings: samples from 20 patients with UC before and after FMT and samples from 18 healthy volunteers.<br><br>RESULTS: Clinical remission was achieved in 19 (95%) patients at week 8. Adverse events occurred in five patients, including one non-responder. A significant increase in average biodiversity was shown in samples after FMT compared to samples before FMT, as well as a decrease in the proportion of some potentially pathogenic bacteria.<br><br>CONCLUSION: The efficacy of FMT for UC treatment was confirmed; however, the duration of remission varied substantially, possibly due to different characteristics of the initial microbiota of patients. Targeted analysis of a patient's microbiome before FMT could increase the treatment efficacy.}, }
@article {pmid38137679, year = {2023}, author = {Tsogka, A and Kitsos, DK and Stavrogianni, K and Giannopapas, V and Chasiotis, A and Christouli, N and Tsivgoulis, G and Tzartos, JS and Giannopoulos, S}, title = {Modulating the Gut Microbiome in Multiple Sclerosis Management: A Systematic Review of Current Interventions.}, journal = {Journal of clinical medicine}, volume = {12}, number = {24}, pages = {}, pmid = {38137679}, issn = {2077-0383}, abstract = {This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple sclerosis (MS), including dietary protocols, probiotics, fecal microbiota transplantation (FMT), and intermittent fasting (IF). Methods: Thirteen studies were held between 2011 and 2023 this demonstrated interventions in gut microbiome among patients with MS and their impact the clinical parameters of the disease. These included specialized dietary interventions, the supply of probiotic mixtures, FMT, and IF. Results: Dietary interventions positively affected various aspects of MS, including relapse rates, EDSS disability scores, MS-related fatigue, and metabolic features. Probiotic mixtures showed promising results on MS-related fatigue, EDSS parameters, inflammation; meanwhile, FMT-though a limited number of studies was included-indicated some clinical improvement in similar variables. IF showed reductions in EDSS scores and significant improvement in patients' emotional statuses. Conclusions: In dietary protocols, clinical MS parameters, including relapse rate, EDSS, MFIS, FSS, and MSQoL54 scales, were significantly improved through the application of a specific diet each time. Probiotic nutritional mixtures promote a shift in inflammation towards an anti-inflammatory cytokine profile in patients with MS. The administration of such mixtures affected disability, mood levels, and quality of life among patients with MS. FMT protocols possibly demonstrate a therapeutic effect in some case reports. IF protocols were found to ameliorate EDSS and FAMS scores. All interventional means of gut microbiome modulation provided significant conclusions on several clinical aspects of MS and highlight the complexity in the relationship between MS and the gut microbiome.}, }
@article {pmid38137495, year = {2023}, author = {Li, A and Bowen, JM and Ball, IA and Wilson, S and Yong, A and Yeung, DT and Lee, CH and Bryant, RV and Costello, SP and Ryan, FJ and Wardill, HR}, title = {Autologous Faecal Microbiota Transplantation to Improve Outcomes of Haematopoietic Stem Cell Transplantation: Results of a Single-Centre Feasibility Study.}, journal = {Biomedicines}, volume = {11}, number = {12}, pages = {}, pmid = {38137495}, issn = {2227-9059}, support = {APP1140992//National Health and Medical Research Council/ ; 2021/81-QA25313//Hospital Research Foundation/ ; 9766//Royal Adelaide Hospital/ ; }, abstract = {Haematopoietic stem cell transplantation (HSCT) is a curative approach for blood cancers, yet its efficacy is undermined by a range of acute and chronic complications. In light of mounting evidence to suggest that these complications are linked to a dysbiotic gut microbiome, we aimed to evaluate the feasibility of faecal microbiota transplantation (FMT) delivered during the acute phase after HSCT. Of note, this trial opted for FMT prepared using the individual's own stool (autologous FMT) to mitigate the risks of disease transmission from a donor stool. Adults (>18 years) with multiple myeloma were recruited from a single centre. The stool was collected prior to starting first line therapy. Patients who progressed to HSCT were offered FMT via 3 × retention enemas before day +5 (HSCT = day 0). The feasibility was determined by the recruitment rate, number and volume of enemas administered, and the retention time. Longitudinally collected stool samples were also collected to explore the influence of auto-FMT using 16S rRNA gene sequencing. n = 4 (2F:2M) participants received auto-FMT in 12 months. Participants received an average of 2.25 (1-3) enemas 43.67 (25-50) mL total, retained for an average of 60.78 (10-145) min. No adverse events (AEs) attributed to the FMT were identified. Although the minimum requirements were met for the volume and retention of auto-FMT, the recruitment was significantly impacted by the logistical challenges of the pretherapy stool collection. This ultimately undermined the feasibility of this trial and suggests that third party (donor) FMT should be prioritised.}, }
@article {pmid38137365, year = {2023}, author = {Świrkosz, G and Szczygieł, A and Logoń, K and Wrześniewska, M and Gomułka, K}, title = {The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis-A Literature Review.}, journal = {Biomedicines}, volume = {11}, number = {12}, pages = {}, pmid = {38137365}, issn = {2227-9059}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum. UC's pathogenesis involves colonic epithelial cell abnormalities and mucosal barrier dysfunction, leading to recurrent mucosal inflammation. The purpose of the article is to show the complex interplay between ulcerative colitis and the microbiome. The literature search was conducted using the PubMed database. After a screening process of studies published before October 2023, a total of 136 articles were selected. It has been discovered that there is a fundamental correlation of a robust intestinal microbiota and the preservation of gastrointestinal health. Dysbiosis poses a grave risk to the host organism. It renders the host susceptible to infections and has been linked to the pathogenesis of chronic diseases, with particular relevance to conditions such as ulcerative colitis. Current therapeutic strategies for UC involve medications such as aminosalicylic acids, glucocorticoids, and immunosuppressive agents, although recent breakthroughs in monoclonal antibody therapies have significantly improved UC treatment. Furthermore, modulating the gut microbiome with specific compounds and probiotics holds potential for inflammation reduction, while fecal microbiota transplantation shows promise for alleviating UC symptoms. This review provides an overview of the gut microbiome's role in UC pathogenesis and treatment, emphasizing areas for further research.}, }
@article {pmid38137038, year = {2023}, author = {Nohesara, S and Abdolmaleky, HM and Zhou, JR and Thiagalingam, S}, title = {Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies.}, journal = {Genes}, volume = {14}, number = {12}, pages = {}, pmid = {38137038}, issn = {2073-4425}, support = {R01 CA138509/CA/NCI NIH HHS/United States ; R21 CA165707/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Depressive Disorder, Major/drug therapy/genetics ; *Microbiota ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use/pharmacology ; Epigenesis, Genetic ; }, abstract = {Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes, drugs, and diet, are involved in the pathogenesis of depressive disorders. However, the underlying mechanisms of depression are complex and include the interaction of genetics with epigenetics and the host immune system. Modifications of the gut microbiome and its metabolites influence stress-related responses and social behavior in patients with depressive disorders by modulating the maturation of immune cells and neurogenesis in the brain mediated by epigenetic modifications. Here, we discuss the potential roles of a leaky gut in the development of depressive disorders via changes in gut microbiota-derived metabolites with epigenetic effects. Next, we will deliberate how altering the gut microbiome composition contributes to the development of depressive disorders via epigenetic alterations. In particular, we focus on how microbiota-derived metabolites such as butyrate as an epigenetic modifier, probiotics, maternal diet, polyphenols, drugs (e.g., antipsychotics, antidepressants, and antibiotics), and fecal microbiota transplantation could positively alleviate depressive-like behaviors by modulating the epigenetic landscape. Finally, we will discuss challenges associated with recent therapeutic approaches for depressive disorders via microbiome-related epigenetic shifts, as well as opportunities to tackle such problems.}, }
@article {pmid38134862, year = {2024}, author = {Zhang, Z and Zuo, L and Song, X and Wang, L and Zhang, Y and Cheng, Y and Huang, J and Zhao, T and Yang, Z and Zhang, H and Li, J and Zhang, X and Geng, Z and Wang, Y and Ge, S and Hu, J}, title = {Arjunolic acid protects the intestinal epithelial barrier, ameliorating Crohn's disease-like colitis by restoring gut microbiota composition and inactivating TLR4 signalling.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {123}, number = {}, pages = {155223}, doi = {10.1016/j.phymed.2023.155223}, pmid = {38134862}, issn = {1618-095X}, mesh = {Mice ; Animals ; *Crohn Disease/drug therapy/metabolism/pathology ; Interleukin-10/metabolism ; *Gastrointestinal Microbiome ; Toll-Like Receptor 4/metabolism ; Lipopolysaccharides/adverse effects ; *Colitis/chemically induced/drug therapy/metabolism ; Inflammation/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Dextran Sulfate/adverse effects ; Colon/pathology ; *Triterpenes ; }, abstract = {BACKGROUND AND AIMS: Crohn's disease (CD) is characterized by an overabundance of epithelial cell death and an imbalance in microflora, both of which contribute to the dysfunction of the intestinal barrier. Arjunolic acid (AA) has anti-apoptotic effects and regulates microbiota efficacy. The objective of this study was to assess the impact of the treatment on colitis resembling Crohn's disease, along with exploring the potential underlying mechanism.<br><br>METHODS: CD animal models were created using Il-10[-/-] mice, and the impact of AA on colitis in mice was evaluated through disease activity index, weight fluctuations, pathological examination, and assessment of intestinal barrier function. To clarify the direct role of AA on intestinal epithelial cell apoptosis, organoids were induced by LPS, and TUNEL staining was performed. To investigate the potential mechanisms of AA in protecting the intestinal barrier, various methods including bioinformatics analysis and FMT experiments were employed.<br><br>RESULTS: The treatment for AA enhanced the condition of colitis and the function of the intestinal barrier in Il-10[-/-] mice. This was demonstrated by the amelioration of weight loss, reduction in tissue inflammation score, and improvement in intestinal permeability. Moreover, AA suppressed the apoptosis of intestinal epithelial cells in Il-10[-/-] mice and LPS-induced colon organoids, while also reducing the levels of Bax and C-caspase-3. In terms of mechanism, AA suppressed the activation of TLR4 signaling in Il-10[-/-] mice and colon organoids induced by LPS. In addition, AA increased the abundance of short-chain fatty acid-producing bacteria in the stool of Il-10[-/-] mice, and transplantation of feces from AA-treated mice improved CD-like colitis.<br><br>CONCLUSIONS: The results of our study demonstrate that AA has a protective effect on the intestinal barrier in Crohn's disease-like colitis by preventing apoptosis. Additionally, this groundbreaking study reveals the capacity of AA to hinder TLR4 signaling and alter the makeup of the intestinal microbiome. The findings present fresh possibilities for treating individuals diagnosed with Crohn's disease. AA offers a hopeful novel strategy for managing Crohn's disease by obstructing crucial pathways implicated in intestinal inflammation and enhancing the gut microbiota.}, }
@article {pmid38134565, year = {2024}, author = {Sah, RK and Nandan, A and Kv, A and S, P and S, S and Jose, A and Venkidasamy, B and Nile, SH}, title = {Decoding the role of the gut microbiome in gut-brain axis, stress-resilience, or stress-susceptibility: A review.}, journal = {Asian journal of psychiatry}, volume = {91}, number = {}, pages = {103861}, doi = {10.1016/j.ajp.2023.103861}, pmid = {38134565}, issn = {1876-2026}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Brain-Gut Axis ; Dysbiosis ; *Resilience, Psychological ; Brain/metabolism ; }, abstract = {Increased exposure to stress is associated with stress-related disorders, including depression, anxiety, and neurodegenerative conditions. However, susceptibility to stress is not seen in every individual exposed to stress, and many of them exhibit resilience. Thus, developing resilience to stress could be a big breakthrough in stress-related disorders, with the potential to replace or act as an alternative to the available therapies. In this article, we have focused on the recent advancements in gut microbiome research and the potential role of the gut-brain axis (GBA) in developing resilience or susceptibility to stress. There might be a complex interaction between the autonomic nervous system (ANS), immune system, endocrine system, microbial metabolites, and bioactive lipids like short-chain fatty acids (SCFAs), neurotransmitters, and their metabolites that regulates the communication between the gut microbiota and the brain. High fiber intake, prebiotics, probiotics, plant supplements, and fecal microbiome transplant (FMT) could be beneficial against gut dysbiosis-associated brain disorders. These could promote the growth of SCFA-producing bacteria, thereby enhancing the gut barrier and reducing the gut inflammatory response, increase the expression of the claudin-2 protein associated with the gut barrier, and maintain the blood-brain barrier integrity by promoting the expression of tight junction proteins such as claudin-5. Their neuroprotective effects might also be related to enhancing the expression of brain-derived neurotrophic factor (BDNF) and glucagon-like peptide (GLP-1). Further investigations are needed in the field of the gut microbiome for the elucidation of the mechanisms by which gut dysbiosis contributes to the pathophysiology of neuropsychiatric disorders.}, }
@article {pmid38133764, year = {2024}, author = {Hiltzik, DM and Goodwin, AM and Kurapaty, SS and Inglis, JE and Pagadala, MS and Edelstein, AI and Hsu, WK}, title = {The Role of the Gut Microbiome in Orthopedic Surgery-a Narrative Review.}, journal = {Current reviews in musculoskeletal medicine}, volume = {17}, number = {2}, pages = {37-46}, pmid = {38133764}, issn = {1935-973X}, abstract = {PURPOSE OF REVIEW: The importance of the gut microbiome has received increasing attention in recent years. New literature has revealed significant associations between gut health and various orthopedic disorders, as well as the potential for interventions targeting the gut microbiome to prevent disease and improve musculoskeletal outcomes. We provide a broad overview of available literature discussing the links between the gut microbiome and pathogenesis and management of orthopedic disorders.<br><br>RECENT FINDINGS: Human and animal models have characterized the associations between gut microbiome dysregulation and diseases of the joints, spine, nerves, and muscle, as well as the physiology of bone formation and fracture healing. Interventions such as probiotic supplementation and fecal transplant have shown some promise in ameliorating the symptoms or slowing the progression of these disorders. We aim to aid discussions regarding optimization of patient outcomes in the field of orthopedic surgery by providing a narrative review of the available evidence-based literature involving gut microbiome dysregulation and its effects on orthopedic disease. In general, we believe that the gut microbiome is a viable target for interventions that can augment current management models and lead to significantly improved outcomes for patients under the care of orthopedic surgeons.}, }
@article {pmid38133321, year = {2023}, author = {Goloshchapov, OV and Shchukina, OB and Kusakin, AV and Tsai, VV and Kalinin, RS and Eismont, YA and Glotov, OS and Chukhlovin, AB}, title = {Next-Generation Sequencing-Based Monitoring of Intestinal Bacteria and Bacteriophages Following Fecal Microbiota Transplantation in Inflammatory Bowel Diseases.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {38133321}, issn = {2076-0817}, support = {22-15-00149//Russian Science Foundation/ ; }, abstract = {Inflammatory bowel diseases (IBD) and acute graft-versus-host disease (GVHD) are associated with persistent intestinal dysfunction preceded by gut bacterial dysbiosis. There are limited data on intestinal bacteriophages in these conditions. The aim of the present work was to detect associations between dominant intestinal bacteria by means of 16S rRNA gene sequencing, and some clinically significant viruses detected with a customized primer panel for NGS-based study. The clinical group included patients with Crohn's disease (IBD, n = 9), or GVHD (n = 6) subjected to fecal microbiota transplantation (FMT) from healthy donors. The stool specimens were taken initially, and 5 times post-FMT until day 120. Using NGS approach, we have found a higher abundance of Proteobacterota phylum in GVHD, especially, at later terms post-FMT. Moreover, we found an early increase of Klebsiella and E. coli/Shigella abundance in GVHD, along with decreased relative content of Faecalibacterium. Upon evaluation of intestinal phageome, the relative amount of Caudoviricetes class was higher in GVHD. A significant correlation was found between Proteobacteria and Caudoviricetes, thus suggesting their association during the post-FMT period. Moreover, the relative amounts of five Caudoviricetes phage species showed distinct correlations with Klebsiella and Enterococcus ratios at different terms of FMT. In conclusion, parallel use of 16S rRNA gene sequencing and targeted NGS viral panel is a feasible and useful option for tracing specific viral strains in fecal microbiota. The developed array of viral primers may be extended to detect other phages infecting the clinically relevant bacteria.}, }
@article {pmid38133287, year = {2023}, author = {Avtanski, D and Reddy, V and Stojchevski, R and Hadzi-Petrushev, N and Mladenov, M}, title = {The Microbiome in the Obesity-Breast Cancer Axis: Diagnostic and Therapeutic Potential.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {38133287}, issn = {2076-0817}, abstract = {A growing body of evidence has demonstrated a relationship between the microbiome, adiposity, and cancer development. The microbiome is emerging as an important factor in metabolic disease and cancer pathogenesis. This review aimed to highlight the role of the microbiome in obesity and its association with cancer, with a particular focus on breast cancer. This review discusses how microbiota dysbiosis may contribute to obesity and obesity-related diseases, which are linked to breast cancer. It also explores the potential of the gut microbiome to influence systemic immunity, leading to carcinogenesis via the modulation of immune function. This review underscores the potential use of the microbiome profile as a diagnostic tool and treatment target, with strategies including probiotics, fecal microbiota transplantation, and dietary interventions. However, this emphasizes the need for more research to fully understand the complex relationship between the microbiome, metabolic disorders, and breast cancer. Future studies should focus on elucidating the mechanisms underlying the impact of the microbiome on breast cancer and exploring the potential of the microbiota profile as a biomarker and treatment target.}, }
@article {pmid38129963, year = {2024}, author = {Cai, J and Cheung, J and Cheung, SWM and Chin, KTC and Leung, RWK and Lam, RST and Sharma, R and Yiu, JHC and Woo, CW}, title = {Butyrate acts as a positive allosteric modulator of the 5-HT transporter to decrease availability of 5-HT in the ileum.}, journal = {British journal of pharmacology}, volume = {181}, number = {11}, pages = {1654-1670}, doi = {10.1111/bph.16305}, pmid = {38129963}, issn = {1476-5381}, support = {202011159091//HKU Internal Seed Fund for Basic Research/ ; 17102920//Hong Kong Research Grant Council/ ; AoE/M-707/18//Hong Kong Research Grant Council/ ; PDFS2021-7S06//Hong Kong RGC Postdoctoral Fellowship Scheme/ ; }, mesh = {Animals ; *Ileum/metabolism/drug effects ; *Serotonin/metabolism ; Humans ; Mice ; Allosteric Regulation/drug effects ; *Butyrates/pharmacology ; Male ; *Gastrointestinal Microbiome/drug effects ; *Serotonin Plasma Membrane Transport Proteins/metabolism ; *Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Diet, High-Fat ; Organoids/drug effects/metabolism ; }, abstract = {BACKGROUND AND PURPOSE: Radiation therapy-induced gastrointestinal distress is partly associated with the elimination of gut microbiota. The effectiveness of 5-HT receptor antagonists to treat radiation therapy-induced emesis implies a pathophysiological role of 5-HT. Peripheral 5-HT is derived from intestinal epithelium. We have investigated the role of gut microbiota in regulating intestinal 5-HT availability.<br><br>EXPERIMENTAL APPROACH: A radiation therapy murine model accompanied by faecal microbiota transplantation from donors fed different diets was investigated, and mouse ileal organoids were used for mechanistic studies. The clinical relevance was validated by a small-scale human study.<br><br>KEY RESULTS: Short-term high-fat diet (HFD) induced gut bacteria to produce butyrate. Irradiated mice receiving HFD-induced microbiome had the lowest ileal levels of 5-HT, compared with other recipients. Treatment with butyrate increased 5-HT uptake in mouse ileal organoids, assayed by the real-time tracking of a fluorescent substrate for monoamine transporters. Silencing the 5-HT transporter (SERT) in the organoids abolished butyrate-stimulated 5-HT uptake. The competitive tests using different types of selective 5-HT reuptake inhibitors suggested that butyrate acted as a positive allosteric modulator of SERT. In human gut microbiota, butyrate production was associated with the interconversion between acetate and butyrate. Faecal contents of both acetate and butyrate were negatively associated with serum 5-HT, but only butyrate was positively correlated with body mass index in humans.<br><br>CONCLUSION AND IMPLICATIONS: Short-term HFD may be beneficial for alleviating gastrointestinal reactions by increasing butyrate to suppress local 5-HT levels and providing energy to cancer patients given radiation therapy.}, }
@article {pmid38129926, year = {2023}, author = {Deng, R and Yu, S and Ruan, X and Liu, H and Zong, G and Cheng, P and Tao, R and Chen, W and Wang, A and Zhao, Y and Wei, Z and Lu, Y}, title = {Capsaicin orchestrates metastasis in gastric cancer via modulating expression of TRPV1 channels and driving gut microbiota disorder.}, journal = {Cell communication and signaling : CCS}, volume = {21}, number = {1}, pages = {364}, pmid = {38129926}, issn = {1478-811X}, support = {BK20200154//Natural Science Foundation of Jiangsu Province/ ; 2020M671551//China Postdoctoral Science Foundation/ ; 82004124//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Animals ; Mice ; Capsaicin/pharmacology ; *Stomach Neoplasms ; *Transient Receptor Potential Channels ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Zebrafish/metabolism ; TRPV Cation Channels/metabolism ; *Antineoplastic Agents ; Zebrafish Proteins/metabolism ; }, abstract = {The association between capsaicin, the major natural pungent compound of chili peppers, and gastric cancer progression has engendered conflicting findings. In this work, we sought to explore the character of a high capsaicin diet in gastric cancer metastasis and its possible mechanism. The impact of high capsaicin consumption on gastric cancer metastasis was investigated in vivo (xenograft mouse and zebrafish models) and in vitro (biochemical and molecular assays). It was demonstrated that high diet of capsaicin gave rise to accelerate tumor metastasis, which was partially mediated by elevating the expression of transient receptor potential vanilloid 1 (TRPV1) in gastric cancer cells. Importantly, we found that genetic depletion of TRPV1 could reduce gastric cancer metastasis by diminishing the motility of tumor cells in vitro, but acted poorly in xenograft mouse model. Considering the distribution of capsaicin in vivo, 16S rRNA sequencing and fecal microbiota transplantation (FMT) were used to appraise whether the gut microbiota involved in the high capsaicin diet induced metastasis. It was demonstrated that the level of Firmicutes and Clostridiales was expressively boosted following the high consumption of capsaicin. This microbial shift contributed to the increased peripheral 5-hydroxytryptamine (5-HT) levels, yielding the aggravated metastatic burden. Collectively, our findings highlighted the potential risk of high capsaicin diet in promoting gastric cancer metastasis by virtue of modulating TRPV1 expression and gut microbiota composition, indicating the importance of controlled consumption of chili peppers for patients with gastric cancer. Video Abstract.}, }
@article {pmid38129370, year = {2023}, author = {Chen, Y and Wang, X and Ye, Y and Ren, Q}, title = {Gut microbiota in cancer: insights on microbial metabolites and therapeutic strategies.}, journal = {Medical oncology (Northwood, London, England)}, volume = {41}, number = {1}, pages = {25}, pmid = {38129370}, issn = {1559-131X}, mesh = {Humans ; *Gastrointestinal Microbiome ; Immunotherapy ; *Neoplasms/therapy ; *Radiation Oncology ; }, abstract = {In recent years, the role of gut microbiota in cancer treatment has attracted substantial attention. It is now well established that gut microbiota and its metabolites significantly contribute to the incidence, treatment, and prognosis of various cancers. This review provides a comprehensive review on the pivotal role of gut microbiota and their metabolites in cancer initiation and progression. Furthermore, it evaluates the impact of gut microbiota on the efficacy and associated side effects of anticancer therapies, including radiotherapy, chemotherapy, and immunotherapy, thus emphasizing the clinical importance of gut microbiota reconstitution in cancer treatment.}, }
@article {pmid38129277, year = {2024}, author = {Bonaz, B}, title = {The gut-brain axis in Parkinson's disease.}, journal = {Revue neurologique}, volume = {180}, number = {1-2}, pages = {65-78}, doi = {10.1016/j.neurol.2023.11.004}, pmid = {38129277}, issn = {0035-3787}, mesh = {Humans ; *Parkinson Disease/therapy/pathology ; Brain-Gut Axis ; *Gastrointestinal Microbiome/physiology ; Brain/pathology ; Central Nervous System ; }, abstract = {There is a bi-directional communication between the gut, including the microbiota, and the brain through the autonomic nervous system. Accumulating evidence has suggested a bidirectional link between gastrointestinal inflammation and neurodegeneration, in accordance with the concept of the gut-rain axis. An abnormal microbiota-gut-brain interaction contributes to the pathogeny of Parkinson's disease. This supports the hypothesis that Parkinson's disease originates in the gut to spread to the central nervous system, in particular through the vagus nerve. Targeting the gut-to-brain axis with vagus nerve stimulation, fecal microbiota transplantation, gut-selective antibiotics, as well as drugs targeting the leaky gut might be of interest in the management of Parkinson's disease.}, }
@article {pmid38128750, year = {2024}, author = {Kim, HN and Cheong, HS and Kim, B and Sohn, W and Cho, YK and Kwon, MJ and Kim, J and Song, Y and Joo, EJ}, title = {Human gut microbiota from hepatitis B virus-infected individuals is associated with reduced triglyceride level in mice: faecal transplantation study.}, journal = {Microbes and infection}, volume = {26}, number = {3}, pages = {105281}, doi = {10.1016/j.micinf.2023.105281}, pmid = {38128750}, issn = {1769-714X}, mesh = {Humans ; Animals ; Mice ; Fecal Microbiota Transplantation/methods ; Hepatitis B virus ; *Gastrointestinal Microbiome ; *Hepatitis B, Chronic ; *Hepatitis B ; *Dyslipidemias ; Triglycerides ; }, abstract = {BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection is associated with a reduced risk of dyslipidaemia. Using a human faecal microbiota transplantation (FMT), we compared changes in gut microbiota and lipid profiles in mice transplanted with human faeces from HBV-infected and non-infected individuals.<br><br>APPROACH AND RESULTS: A total of 19 mice received human FMT from four HBV-infected individuals and were categorised into the HBV-positive mice group, while 20 mice received FMT from four HBV-non-infected individuals into the HBV-negative one. In the analysis of gut microbiota in FMT mice, we observed a robust increase in alpha diversity and abundance of Akkermansia muciniphila in HBV-positive mice, compared to that in HBV-negative. Functional inference analysis revealed that the pathways involved in glycerolipid metabolism were more enriched in HBV-positive mice. At 5 weeks of FMT, the reduced triglyceride (TG) level was predominantly observed in HBV-positive mice.<br><br>CONCLUSIONS: Altered gut microbiota accompanied by HBV infection was associated with a robust increase in alpha diversity and butyrate producers, which resulted in a reduced level of TG at 5 weeks post-FMT. This indicates that the reduced risk of dyslipidaemia in chronic HBV infection may be due to the altered gut microbiota accompanied by HBV infection.}, }
@article {pmid38128454, year = {2024}, author = {Wu, D and Liang, S and Du, X and Xiao, J and Feng, H and Ren, Z and Yang, X and Yang, X}, title = {Effects of fecal microbiota transplantation and fecal virome transplantation on LPS-induced intestinal injury in broilers.}, journal = {Poultry science}, volume = {103}, number = {2}, pages = {103316}, pmid = {38128454}, issn = {1525-3171}, mesh = {Animals ; *Fecal Microbiota Transplantation/veterinary/methods ; Lipopolysaccharides/toxicity ; Chickens ; Virome ; *Intestinal Diseases/veterinary ; RNA, Messenger ; }, abstract = {The interesting roles and efficiencies of fecal microbiota transplantation (FMT) have attracted considerable attention and have been gradually evidenced in specific animal models. While the growing evidence that bacteriophages play roles in FMT efficacy has attracted considerable interest. In this study, we aimed to explore the effects of FMT and fecal virome transplantation (FVT) in improving inflammatory damage and ileal microbiota disorder in broilers. A total of 224 Arbor Acres broilers were selected at 1-day-old and randomly divided into the following 4 groups, with 56 broilers in each group: the CON group (the negative control group, sterile physiological saline injection + sterile phosphate-buffered saline (PBS) solution gavage), LPS group (the positive control group, lipopolysaccharide (LPS) injection + sterile PBS solution gavage), LPS + FMT group (LPS injection + FMT solution gavage), LPS + FVT group (LPS injection + FVT solution gavage). The results showed that: LPS injection significantly upregulated the mRNA expression levels of IFN-γ (P < 0.05) and IL-8 (P < 0.001) in ileal mucosa of broilers at 11th day of age (D11), while LPS + FMT and LPS + FVT did not; LPS injection significantly upregulated the mRNA expression of ZO-1 in ileal mucosa at D11 (P < 0.01), while LPS + FMT and LPS + FVT did not; at D11, compare to CON group, LPS injection and LPS + FMT significantly increased the relative abundance of virulence factor Rab2 interacting conserved protein A-related genes in broiler ileum contents (P < 0.05), while LPS + FVT had no significant difference with CON group (P > 0.05); at D11, LPS injection significantly downregulated the biosynthesis of antibiotics pathway (P < 0.05) in the ileal contents, while LPS + FVT did not. In conclusion, both FMT and FVT could promote the recovery of inflammation caused by LPS. Furthermore, FVT had shown less disadvantage stimulation on the broilers and could reduce the risk of transmission of pathogenic genes, compared to FMT.}, }
@article {pmid38126747, year = {2024}, author = {Peng, J and Liu, T and Meng, P and Luo, Y and Zhu, S and Wang, Y and Ma, M and Han, J and Zhou, J and Su, X and Li, S and Ho, C-T and Lu, C}, title = {Gallic acid ameliorates colitis by trapping deleterious metabolite ammonia and improving gut microbiota dysbiosis.}, journal = {mBio}, volume = {15}, number = {2}, pages = {e0275223}, pmid = {38126747}, issn = {2150-7511}, support = {LY22C010002//MOST | NSFC | NSFC-Zhejiang Joint Fund | | Natural Science Foundation of Zhejiang Province (ZJNSF)/ ; 2022M721732//China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)/ ; NA//K.C. Wong Magna Fund of Ningbo University/ ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Ammonia ; Dysbiosis ; Gallic Acid/adverse effects ; *Colitis/chemically induced ; *Inflammatory Bowel Diseases ; Amino Acids ; Disease Models, Animal ; Mice, Inbred C57BL ; Colon ; }, abstract = {Gut microbiota dysbiosis is causally related to inflammatory bowel disease (IBD), and increased levels of the gut metabolite ammonia have been proposed to contribute to IBD development. In this study, we aimed to clarify the anti-colitis mechanism of gallic acid (GA) based on its ability to trap the deleterious metabolite ammonia and improve gut microbiota. Aminated product was detected in the fecal samples of mice after oral gavage of gallic acid (GA) and identified as 4-amino-substituted gallic acid (4-NH2-GA), thus confirming the ability of GA to trap ammonia in vivo. Then, we compared the beneficial effects of GA and 4-NH2-GA on dextran sulfate sodium (DSS)-induced colitis mouse and found that both compounds managed to alleviate colitis phenotypes, indicating ammonia trapping had no adverse effect on the original anti-colitis activity of GA. In addition, both GA and 4-NH2-GA improved the gut microbiota dysbiosis induced by DSS, and fecal microbiota transplantation was subsequently performed, which further revealed that the gut microbiota mediated the anti-colitis activity of both GA and 4-NH2-GA. In summary, this study clarified that GA alleviated colitis by targeting both the symptoms and root causes: it directly reduced the deleterious metabolite ammonia by forming aminated metabolites without compromising the original anti-colitis activity, and it also improved gut microbiota dysbiosis, which in turn contributed to the alleviation of colitis. Since the GA structure is presented in various polyphenols as a common building block, the novel anti-colitis mechanism obtained from GA may also apply to other complex polyphenols.IMPORTANCEThe dysbiosis of the gut microbiota and its metabolism directly cause the emergence of IBD. In this study, we aimed to clarify the anti-colitis mechanism of GA in sight of gut microbiota and its metabolite ammonia. We discovered that GA directly captured and reduced the harmful metabolite ammonia in vivo to produce the aminated metabolite 4-NH2-GA, while the amination of GA had no adverse effect on its initial anti-colitis activity. In addition, both GA and its aminated metabolite improved the gut microbiota in colitis mice, and the modified gut microbiota, in turn, helped to relieve colitis. Since the GA structure is presented in diverse polyphenols as a common building block, the novel anti-colitis mechanism targeting the symptoms and root causes might also apply to other complex polyphenols.}, }
@article {pmid38126116, year = {2024}, author = {Ma, X and Shin, JW and Cho, JH and Han, SW and Kim, DH}, title = {IL-6 expression-suppressing Lactobacillus reuteri strains alleviate gut microbiota-induced anxiety and depression in mice.}, journal = {Letters in applied microbiology}, volume = {77}, number = {1}, pages = {}, doi = {10.1093/lambio/ovad144}, pmid = {38126116}, issn = {1472-765X}, support = {22203MFDS539//Ministry of Food and Drug Safety/ ; 2017R1A5A2014768//Korea Healthy Industry Development Institute and the Medical Research Program/ ; }, mesh = {Rats ; Humans ; Mice ; Animals ; *Limosilactobacillus reuteri ; Interleukin-6/genetics ; Depression/therapy ; Tumor Necrosis Factor-alpha/genetics ; *Gastrointestinal Microbiome ; Lipopolysaccharides/toxicity ; Corticosterone/pharmacology ; Serotonin/pharmacology ; Brain-Derived Neurotrophic Factor/genetics/metabolism/pharmacology ; *Neuroblastoma ; Anxiety/therapy/etiology ; Mice, Inbred C57BL ; }, abstract = {Fecal microbiota transplantation from patients with depression/inflammatory bowel disease (PDI) causes depression with gut inflammation in mice. Here, we investigated the effects of six Lactobacillus reuteri strains on brain-derived neurotropic factor (BDNF), serotonin, and interleukin (IL)-6 expression in neuronal or macrophage cells and PDI fecal microbiota-cultured microbiota (PcM)-induced depression in mice. Of these strains, L6 most potently increased BDNF and serotonin levels in corticosterone-stimulated SH-SY5Y and PC12 cells, followed by L3. L6 most potently decreased IL-6 expression in lipopolysaccharide (LPS)-stimulated macrophages. When L1 (weakest in vitro), L3, and L6 were orally administered in mice with PcM-induced depression, L6 most potently suppressed depression-like behaviors and hippocampal TNF-α and IL-6 expression and increased hippocampal serotonin, BDNF, 5HT7, GABAARα1, and GABABR1b expression, followed by L3 and L1. L6 also suppressed TNF-α and IL-6 expression in the colon. BDNF or serotonin levels in corticosterone-stimulated neuronal cells were negatively correlated with depression-related biomarkers in PcM-transplanted mice, while IL-6 levels in LPS-stimulated macrophage were positively correlated. These findings suggest that IL-6 expression-suppressing and BDNF/serotonin expression-inducing LBPs in vitro, particularly L6, may alleviate gut microbiota-involved depression with colitis in vivo.}, }
@article {pmid38124157, year = {2023}, author = {Miller, J and Żebrowska-Różańska, P and Czajkowska, A and Szponar, B and Kumala-Ćwikła, A and Chmielarz, M and Łaczmański, &#x141;}, title = {Faecal microbiota and fatty acids in feline chronic enteropathy.}, journal = {BMC veterinary research}, volume = {19}, number = {1}, pages = {281}, pmid = {38124157}, issn = {1746-6148}, support = {N060/0020/20//Wroclaw University of Environmental and Life Sciences, Wroc&#x142;aw, Poland/ ; N060/0020/20//Wroclaw University of Environmental and Life Sciences, Wroc&#x142;aw, Poland/ ; N060/0020/20//Wroclaw University of Environmental and Life Sciences, Wroc&#x142;aw, Poland/ ; }, mesh = {Cats ; Animals ; Fatty Acids/analysis ; RNA, Ribosomal, 16S/genetics/analysis ; Fatty Acids, Volatile/analysis ; *Inflammatory Bowel Diseases/veterinary ; Feces/microbiology ; *Microbiota ; *Cat Diseases ; }, abstract = {BACKGROUND: Feline chronic enteropathy is a set of disorders defined as the presence of clinical signs of gastrointestinal disease for at least three weeks. The most common final diagnoses are inflammatory bowel disease and alimentary small cell lymphoma. The etiopathogenesis of these diseases is incompletely understood; however, it is hypothesised that they involve a combination of factors, including altered composition and/or functionality of the intestinal microbiome. An important factor in the interplay of the microbiome and host is the production of short- and branched-chain fatty acids. The aim of this study was to evaluate the possible differences in faecal microbiota diversity, composition and fatty acid production between cats suffering from chronic enteropathy and healthy cats. Sixteen cats suffering from chronic enteropathy and fourteen healthy control cats were enrolled in the study. The microbiota compositions of faecal samples were analysed by using next-generation amplicon sequencing of the V3V4 fragment of the 16S rRNA gene. Fatty acids were evaluated by high-performance liquid chromatography.<br><br>RESULTS: Both the alpha and beta diversities were significantly lower in samples obtained from cats with chronic enteropathy. The relative abundance of the phylum Proteobacteria, orders Lactobacillales and Enterobacterales, family Enteriobacteriaceae and genus Escherichia Shigella were higher in diseased cats, whereas the abundance of the phylum Bacteroidota and order Peptococcales were higher in control cats. The faecal concentrations of short-chain fatty acids were higher in cats with chronic enteropathy, with lower propionate proportions and higher butyrate proportions.<br><br>CONCLUSION: The study revealed alterations in microbiota compositions and short-chain fatty acid concentration in cats suffering from chronic enteropathy, which is an important finding both for research on the pathogenesis of the disease and for potential therapeutic interventions in the form of faecal microbiota transplantation and/or probiotic supplementation.}, }
@article {pmid38124090, year = {2023}, author = {Bleich, RM and Li, C and Sun, S and Ahn, JH and Dogan, B and Barlogio, CJ and Broberg, CA and Franks, AR and Bulik-Sullivan, E and Carroll, IM and Simpson, KW and Fodor, AA and Arthur, JC}, title = {A consortia of clinical E. coli strains with distinct in vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {277}, pmid = {38124090}, issn = {2049-2618}, support = {P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30DK034987/NH/NIH HHS/United States ; K12 GM000678/GM/NIGMS NIH HHS/United States ; R21 AI159786/AI/NIAID NIH HHS/United States ; K01 DK103952/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Young Adult ; Dysbiosis/complications ; Escherichia coli/genetics ; *Escherichia coli Infections/microbiology ; *Gastrointestinal Microbiome ; Inflammation/metabolism ; Interleukin-10 ; Intestinal Mucosa/microbiology ; RNA, Ribosomal, 16S/genetics/metabolism ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in vitro definition fully predicts mucosal colonization in vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis.<br><br>RESULTS: Germ-free inflammation-susceptible interleukin-10-deficient (Il10[-/-]) and inflammation-resistant WT mice were colonized with a consortium of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10[-/-] mice. These E. coli expand in Il10[-/-] mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization.<br><br>CONCLUSIONS: Our findings establish the in vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in vivo colonization dynamics of patient-derived bacteria in murine models. Video Abstract.}, }
@article {pmid38123016, year = {2024}, author = {Gonçalves, CL and Doifode, T and Rezende, VL and Costa, MA and Rhoads, JM and Soutullo, CA}, title = {The many faces of microbiota-gut-brain axis in autism spectrum disorder.}, journal = {Life sciences}, volume = {337}, number = {}, pages = {122357}, doi = {10.1016/j.lfs.2023.122357}, pmid = {38123016}, issn = {1879-0631}, mesh = {Humans ; Brain-Gut Axis ; *Autism Spectrum Disorder/therapy ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; *Gastrointestinal Diseases/drug therapy ; }, abstract = {The gut-brain axis is gaining more attention in neurodevelopmental disorders, especially autism spectrum disorder (ASD). Many factors can influence microbiota in early life, including host genetics and perinatal events (infections, mode of birth/delivery, medications, nutritional supply, and environmental stressors). The gut microbiome can influence blood-brain barrier (BBB) permeability, drug bioavailability, and social behaviors. Developing microbiota-based interventions such as probiotics, gastrointestinal (GI) microbiota transplantation, or metabolite supplementation may offer an exciting approach to treating ASD. This review highlights that RNA sequencing, metabolomics, and transcriptomics data are needed to understand how microbial modulators can influence ASD pathophysiology. Due to the substantial clinical heterogeneity of ASD, medical caretakers may be unlikely to develop a broad and effective general gut microbiota modulator. However, dietary modulation followed by administration of microbiota modulators is a promising option for treating ASD-related behavioral and gastrointestinal symptoms. Future work should focus on the accuracy of biomarker tests and developing specific psychobiotic agents tailored towards the gut microbiota seen in ASD patients, which may include developing individualized treatment options.}, }
@article {pmid38118419, year = {2023}, author = {Quesada-Vázquez, S and Castells-Nobau, A and Latorre, J and Oliveras-Cañellas, N and Puig-Parnau, I and Tejera, N and Tobajas, Y and Baudin, J and Hildebrand, F and Beraza, N and Burcelin, R and Martinez-Gili, L and Chilloux, J and Dumas, ME and Federici, M and Hoyles, L and Caimari, A and Del Bas, JM and Escoté, X and Fernández-Real, JM and Mayneris-Perxachs, J}, title = {Potential therapeutic implications of histidine catabolism by the gut microbiota in NAFLD patients with morbid obesity.}, journal = {Cell reports. Medicine}, volume = {4}, number = {12}, pages = {101341}, pmid = {38118419}, issn = {2666-3791}, mesh = {Humans ; Mice ; Rats ; Animals ; *Non-alcoholic Fatty Liver Disease/drug therapy ; Histidine/therapeutic use ; *Obesity, Morbid ; *Gastrointestinal Microbiome/physiology ; Diet, High-Fat ; }, abstract = {The gut microbiota contributes to the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Histidine is a key energy source for the microbiota, scavenging it from the host. Its role in NAFLD is poorly known. Plasma metabolomics, liver transcriptomics, and fecal metagenomics were performed in three human cohorts coupled with hepatocyte, rodent, and Drosophila models. Machine learning analyses identified plasma histidine as being strongly inversely associated with steatosis and linked to a hepatic transcriptomic signature involved in insulin signaling, inflammation, and trace amine-associated receptor 1. Circulating histidine was inversely associated with Proteobacteria and positively with bacteria lacking the histidine utilization (Hut) system. Histidine supplementation improved NAFLD in different animal models (diet-induced NAFLD in mouse and flies, ob/ob mouse, and ovariectomized rats) and reduced de novo lipogenesis. Fecal microbiota transplantation (FMT) from low-histidine donors and mono-colonization of germ-free flies with Enterobacter cloacae increased triglyceride accumulation and reduced histidine content. The interplay among microbiota, histidine catabolism, and NAFLD opens therapeutic opportunities.}, }
@article {pmid38118418, year = {2023}, author = {Liu, X and Xu, B and Xu, X and Wang, Z and Luo, Y and Gao, Y and Ling, S and Wang, A and Zhou, Y and Wang, X and Leng, SX and Li, W and Yao, X}, title = {Attenuation of allergen-specific immunotherapy for atopic dermatitis by ectopic colonization of Brevundimonas vesicularis in the intestine.}, journal = {Cell reports. Medicine}, volume = {4}, number = {12}, pages = {101340}, pmid = {38118418}, issn = {2666-3791}, mesh = {*Dermatitis, Atopic/therapy ; Caulobacteraceae ; Intestines ; Allergens ; Humans ; Mice ; Desensitization, Immunologic ; Animals ; }, abstract = {Allergen-specific immunotherapy (AIT) has shown beneficial effects against atopic dermatitis (AD); however, the mechanisms and parameters underlying the efficacy of AIT remain unclear. Here, we report that the community structure and function of the oral and gut microbiota are changed in patients with AD undergoing AIT. Transplantation of fecal microbiota from patients who respond well to AIT improves AD-like dermatitis in mice. The abundance of Brevundimonas vesicularis in the gut of AD patients has been found to be positively correlated with disease severity and is decreased following AIT. Furthermore, we find that B. vesicularis from the oral cavity might ectopically colonize the gut of AD patients. In AD model mice, meanwhile, B. vesicularis promotes the skewing of the Treg/Th17 balance toward Th17 polarization and attenuates the efficacy of ovalbumin-specific immunotherapy. Our findings provide potential strategies for the optimization of AIT for AD via the modulation of the gut microbiota.}, }
@article {pmid38116809, year = {2024}, author = {Ren, P and Yue, H and Tang, Q and Wang, Y and Xue, C}, title = {Astaxanthin slows down skeletal muscle atrophy in H22 tumor-bearing mice during sorafenib treatment by modulating the gut microbiota.}, journal = {Food &amp; function}, volume = {15}, number = {2}, pages = {543-558}, doi = {10.1039/d3fo04633h}, pmid = {38116809}, issn = {2042-650X}, mesh = {Mice ; Humans ; Animals ; Sorafenib ; *Gastrointestinal Microbiome ; Muscular Atrophy/metabolism ; Muscle, Skeletal/metabolism ; *Neoplasms/metabolism ; Xanthophylls ; }, abstract = {Astaxanthin is a carotenoid that is taken orally and has antitumor and anti-inflammatory properties. Our previous research demonstrated that astaxanthin alleviated skeletal muscle atrophy during sorafenib treatment in H22 tumor-bearing mice and altered the intestinal flora composition. However, the relationship between astaxanthin's amelioration of skeletal muscle atrophy in tumor-bearing mice and its ability to regulate intestinal flora is not clear. We used broad-spectrum antibiotics to create pseudo-sterile tumor-bearing mice, which we then used in fecal bacteria transplantation experiments. Our results indicate that the role of astaxanthin in ameliorating skeletal muscle atrophy during molecularly targeted therapy in mice with tumors is dependent on the intestinal flora. Astaxanthin substantially promoted the proliferation of Blautia, Parabacteroides, and Roseburia, altered the levels of metabolites in mouse serum, and primarily affected the amino acid metabolism of mice. Astaxanthin ameliorated skeletal muscle atrophy by promoting the activation of AKT/FOXO3a, which inhibited the expression of ubiquitination-degrading Fbx32 and MuRF1 and promoted myogenesis in skeletal muscle. Our study confirms that the intestinal flora is an important target for astaxanthin to combat skeletal muscle atrophy. Our research supports the use of astaxanthin as a nutritional supplement and intestinal microecological regulator for cancer patients.}, }
@article {pmid38115597, year = {2024}, author = {Li, X and Li, J and Ji, J and Li, S and Yao, X and Fan, H and Yao, R}, title = {Gut microbiota modification by diosgenin mediates antiepileptic effects in a mouse model of epilepsy.}, journal = {Journal of neurochemistry}, volume = {168}, number = {12}, pages = {3982-4000}, doi = {10.1111/jnc.16033}, pmid = {38115597}, issn = {1471-4159}, support = {KYCX22_2869//Graduate Research and Innovation Projects of Jiangsu Province/ ; BK20221221//Natural Science Foundation of Jiangsu Province/ ; }, mesh = {Animals ; *Diosgenin/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Mice ; Male ; *Epilepsy/drug therapy ; *Disease Models, Animal ; *Anticonvulsants/pharmacology/therapeutic use ; *Mice, Inbred C57BL ; Pentylenetetrazole/toxicity ; Fecal Microbiota Transplantation ; }, abstract = {Diosgenin, a natural steroid saponin, holds promise as a multitarget therapeutic for various diseases, including neurodegenerative conditions. Its efficacy in slowing Alzheimer's disease, Parkinson's disease, multiple sclerosis, and stroke progression has been demonstrated. However, the role of diosgenin in anti-epilepsy and its potential connection to the modulation of the intestinal microbiota remain poorly understood. In this study, exogenous diosgenin significantly mitigated pentylenetetrazole (PTZ)-induced seizures, learning and memory deficits, and hippocampal neuronal injury. 16S ribosomal RNA (16S rRNA) sequencing revealed a reversal in the decrease of Bacteroides and Parabacteroides genera in the PTZ-induced mouse epileptic model following diosgenin treatment. Fecal microbiota transplantation (FMT) experiments illustrated the involvement of diosgenin in modulating gut microbiota and providing neuroprotection against epilepsy. Our results further indicated the repression of enteric glial cells (EGCs) activation and the TLR4-MyD88 pathway, coupled with reduced production of inflammatory cytokines in the colonic lumen, and improved intestinal barrier function in epilepsy mice treated with diosgenin or FMT. This study suggests that diosgenin plays a role in modifying gut microbiota, contributing to the alleviation of intestinal inflammation and neuroinflammation, ultimately inhibiting epilepsy progression in a PTZ-induced mouse model. Diosgenin emerges as a potential therapeutic option for managing epilepsy and its associated comorbidities.}, }
@article {pmid38113887, year = {2024}, author = {Zhu, Y and Jian, X and Chen, S and An, G and Jiang, D and Yang, Q and Zhang, J and Hu, J and Qiu, Y and Feng, X and Guo, J and Chen, X and Li, Z and Zhou, R and Hu, C and He, N and Shi, F and Huang, S and Liu, H and Li, X and Xie, L and Zhu, Y and Zhao, L and Jiang, Y and Li, J and Wang, J and Qiu, L and Chen, X and Jia, W and He, Y and Zhou, W}, title = {Targeting gut microbial nitrogen recycling and cellular uptake of ammonium to improve bortezomib resistance in multiple myeloma.}, journal = {Cell metabolism}, volume = {36}, number = {1}, pages = {159-175.e8}, doi = {10.1016/j.cmet.2023.11.019}, pmid = {38113887}, issn = {1932-7420}, mesh = {Humans ; Bortezomib/pharmacology/therapeutic use/metabolism ; *Multiple Myeloma/drug therapy/metabolism ; *Gastrointestinal Microbiome ; Cell Line, Tumor ; Membrane Proteins/metabolism ; NIMA-Related Kinases/metabolism/therapeutic use ; Solute Carrier Family 12, Member 2/pharmacology ; }, abstract = {The gut microbiome has been found to play a crucial role in the treatment of multiple myeloma (MM), which is still considered incurable due to drug resistance. In previous studies, we demonstrated that intestinal nitrogen-recycling bacteria are enriched in patients with MM. However, their role in MM relapse remains unclear. This study highlights the specific enrichment of Citrobacter freundii (C. freundii) in patients with relapsed MM. Through fecal microbial transplantation experiments, we demonstrate that C. freundii plays a critical role in inducing drug resistance in MM by increasing levels of circulating ammonium. The ammonium enters MM cells through the transmembrane channel protein SLC12A2, promoting chromosomal instability and drug resistance by stabilizing the NEK2 protein. We show that furosemide sodium, a loop diuretic, downregulates SLC12A2, thereby inhibiting ammonium uptake by MM cells and improving progression-free survival and curative effect scores. These findings provide new therapeutic targets and strategies for the intervention of MM progression and drug resistance.}, }
@article {pmid38113632, year = {2024}, author = {Wang, J and Xin, J and Xu, X and Chen, W and Lv, Y and Wei, Y and Wei, X and Li, Z and Ding, Q and Zhao, H and Wen, Y and Zhang, X and Fang, Y and Zu, X}, title = {Bacopaside I alleviates depressive-like behaviors by modulating the gut microbiome and host metabolism in CUMS-induced mice.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {170}, number = {}, pages = {115679}, doi = {10.1016/j.biopha.2023.115679}, pmid = {38113632}, issn = {1950-6007}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Depression/metabolism ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Antidepressive Agents/pharmacology/therapeutic use ; Acetates/pharmacology ; Stress, Psychological/metabolism ; }, abstract = {Bacopaside I (BSI) is a natural compound that is difficult to absorb orally but has been shown to have antidepressant effects. The microbiota-gut-brain axis is involved in the development of depression through the peripheral nervous system, endocrine system, and immune system and may be a key factor in the effect of BSI. Therefore, this study aimed to investigate the potential mechanism of BSI in the treatment of depression via the microbiota-gut-brain axis and to validate it in a fecal microbiota transplantation model. The antidepressant effect of BSI was established in CUMS-induced mice using behavioral tests and measurement of changes in hypothalamicpituitaryadrenal (HPA) axis-related hormones. The improvement of stress-induced gut-brain axis damage by BSI was observed by histopathological sections and enzyme-linked immunosorbent assay (ELISA). 16 S rDNA sequencing analysis indicated that BSI could modulate the abundance of gut microbiota and increase the abundance of probiotic bacteria. We also observed an increase in short-chain fatty acids, particularly acetic acid. In addition, BSI could modulate the disruption of lipid metabolism induced by CUMS. Fecal microbiota transplantation further confirmed that disruption of the microbiota-gut-brain axis is closely associated with the development of depression, and that the microbiota regulated by BSI exerts a partial antidepressant effect. In conclusion, BSI exerts antidepressant effects by remodeling gut microbiota, specifically through the Lactobacillus and Streptococcus-acetic acid-neurotrophin signaling pathways. Furthermore, BSI can repair damage to the gut-brain axis, regulate HPA axis dysfunction, and maintain immune homeostasis.}, }
@article {pmid38112268, year = {2024}, author = {Chen, C and Liang, ZF and He, YQ and Li, AQ and Gao, Y and Pan, QW and Cao, JS}, title = {Pravastatin promotes type 2 diabetes vascular calcification through activating intestinal Bacteroides fragilis to induce macrophage M1 polarization.}, journal = {Journal of diabetes}, volume = {16}, number = {6}, pages = {e13514}, pmid = {38112268}, issn = {1753-0407}, support = {2021JJ40490//Natural Science Foundation of Hunan Province, China/ ; 2021JJ70113//Natural Science Foundation of Hunan Province, China/ ; 22A0292//The Research Foundation of Education Bureau of Hunan Province, China/ ; }, mesh = {*Pravastatin/pharmacology ; Animals ; *Vascular Calcification/metabolism/etiology/pathology ; Mice ; *Macrophages/metabolism/drug effects ; Humans ; *Diabetes Mellitus, Type 2/drug therapy/metabolism ; *Bacteroides fragilis ; Male ; Gastrointestinal Microbiome/drug effects ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Mice, Inbred C57BL ; Female ; }, abstract = {BACKGROUND: Pravastatin is an oral lipid-lowering drug, commonly used by patients with diabetes that is positively correlated with the occurrence of vascular calcification (VC), but the mechanism is unclear.<br><br>METHODS: In this study, 16S rRNA sequencing and qRT-PCR wereused to detect the differential gut bacteria. Metabolomics and ELISA were used to analyze the differential metabolites. qRT-PCR and western blotting (WB) were used to detect genes expression. Flow cytometry was used to analyze macrophage phenotype. Immunohistochemistry was used to analyze aortic calcification.<br><br>RESULTS: We found that gut Bacteroides fragilis (BF) increased significantly in patients who took pravastatin or type 2 diabetes (T2D) mice treated with pravastatin. In vitro experiments showed that pravastatin had little effect on BF but significantly promoted BF proliferation in vivo. Further analysis showed that ArsR was an important gene for pravastatin to regulate the activation of BF, and overexpression of ArsR significantly promoted the secretion of 3,4,5-trimethoxycinnamic acid (TMCA). Importantly, pravastatin significantly promoted BF secretion of TMCA and significantly increased TMCA secretion in T2D patients or T2D mice. TMCA had little effect on vascular smooth muscle cell calcification but significantly promoted macrophage M1 polarization, which we had demonstrated that M1 macrophages promoted T2D VC. In vivo studies found that pravastatin significantly upregulated TMCA levels in the feces and serum of T2D mice transplanted with BF and promoted the macrophage M1 polarization in bone marrow and the osteoblastic differentiation of aortic cells. Similar results were obtained in T2D mice after intravenous infusion of TMCA.<br><br>CONCLUSIONS: Promoting intestinal BF to secrete TMCA, which leads to macrophage M1 polarization, is an important mechanism by which pravastatin promotes calcification, and the result will be used for the optimization of clinical medication strategies of pravastatin supplying a theoretical basis and experimental basis.}, }
@article {pmid38111204, year = {2023}, author = {Song, Y and Yu, J and Wang, B and Wen, Q and Zhong, Y and Wu, M and Zheng, X}, title = {Effect of fecal microbiota transplantation on early intestinal immune function and histomorphology of immune organs in chicks.}, journal = {Letters in applied microbiology}, volume = {76}, number = {12}, pages = {}, doi = {10.1093/lambio/ovad140}, pmid = {38111204}, issn = {1472-765X}, support = {21ZGN16//Changchun Key R&amp;D Program/ ; 20230508004RC//Middle and Young People Project of Jilin Province/ ; }, mesh = {Animals ; Female ; *Fecal Microbiota Transplantation/methods ; *Chickens ; Fatty Acids, Volatile ; Butyric Acid ; Immunity ; }, abstract = {UNLABELLED: The intestinal microbiota drives the maturation of the immune system, which is essential for maintaining lifetime homeostasis. Whether fecal microbiota transplantation can promote the development of the immune system in chicks? On days 1, 3, and 5, the post-hatch Hy-line Brown chicks were treated with fecal suspension from breeding hens. Intestinal length, blood biochemical indicators, the morphology of immune organs, and intestinal immunity-related indicators were focused on days 7 and 14. Short-chain fatty acids were determined by gas chromatography. We discovered that fecal microbial transplantation significantly increased the area of the follicles and medulla from the bursa of Fabricius, as well as the area of the medulla, cortex, and both ratios from the thymus on 14 d, the concentration of butyric acid in feces, the levels of immunologically active substances (transforming growth factor-β, interleukin 10, forkhead box protein P3, G-Protein Coupled Receptor 43, immunoglobulin A, etc.) in serum or the intestine, and the number of goblet cells. Correlation analysis indicated that short-chain fatty acids, as metabolites of the gut microbiota, were correlated with intestinal immunity. In short, fecal microbiota transplantation regulated early intestinal immunity, which provided the possibility for the processing and utilization of gut microbiota as germplasm resources.<br><br>IMPACT STATEMENT: Modern management of eggs causes the normal vertical transmission of microbiota from hens to be significantly reduced. The risk of environmental threats to newborn chicks is raised. The microbial community helps to mature the immune system of chicks and protect them from pathogen invasion. We still have doubts about whether transplanting the microbiota can regulate gut immunity. Using the gut microbiota of hens as an excellent resource to improve the immunity of chicks may provide new ideas for the development of the poultry industry.}, }
@article {pmid38110638, year = {2023}, author = {Xie, B and Wang, B and Shang, R and Wang, L and Huang, X and Xie, L}, title = {Blocking MyD88 signaling with MyD88 inhibitor prevents colitis-associated colorectal cancer development by maintaining colonic microbiota homeostasis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {22552}, pmid = {38110638}, issn = {2045-2322}, support = {2021CFB401//the Hubei Provincial Natural Science Foundation of China/ ; WJ2023M014//the Hubei Province health and family planning scientific research project/ ; 2020QYKF02//Open Project of the Key Laboratory of Organ Transplantation, Ministry of Education, and NHC/ ; 81702817//National Natural Science Foundations for Young Scientists of China/ ; 82273309//National Natural Science Foundations of China/ ; }, mesh = {Animals ; Mice ; *Colitis/complications/microbiology ; *Colitis-Associated Neoplasms ; Colon/metabolism ; Dextran Sulfate ; Disease Models, Animal ; Mice, Inbred C57BL ; *Myeloid Differentiation Factor 88/antagonists &amp; inhibitors/metabolism ; Signal Transduction ; *Gastrointestinal Microbiome ; }, abstract = {Certain intestinal microbiota alterations appear to positively correlate with tumorigenesis of CAC due to the disruption of the balance between the host and microorganisms. It is proven that blocking MyD88 signaling can prevent colitis-associated colorectal cancer (CAC) development in mice. We are aim to reveal the role of MyD88 signaling of maintaining colonic microbiota homeostasis for preventing CAC development. We here analyzed the landscape of gut microbiome in the mice model of AOM/DSS-induced CAC with MyD88 inhibitor treatment. PCoA revealed significant reduction in Lactobacillus load and increase in Escherichia load in the mucosal microbial composition of mice with CAC, compared with normal controls (NCs). Inhibitor-treatment led to almost undetectable Proteobacteria (Escherichia) and the retention of the dominance of Firmicutes and Bacteroidota (Muribaculaceae) in the mucosa. RNA sequencing analysis identified genes were up-regulated (Hp, SAA3 and IL-1F9) and down-regulated (CYP3A44, SLC30A10, GPNMB and OTC) in Inhibitor-treated mice (vs. CAC). Meanwhile, Inhibitor-treated mice had higher percentage of MUC2-positive area in colon sections (vs. CAC, which was less than NCs) by IF staining and decreased Escherichia in the mucus layer (vs. CAC) by FISH. And intestinal microbiota from mice with MyD88 inhibitor treatment could lessen the outcome of CAC by fecal microbiota transplantation. The development of CAC was involved in the increasing and ectopic Escherichia in the decreasing colonic mucus layer. MyD88 signaling blockade may maintain the host-microbiota homeostasis by up-regulating MUC2 production, increasing probiotics and their protective effects, and inhibiting the reproduction of Escherichia.}, }
@article {pmid38109364, year = {2024}, author = {Pun, CK and Huang, HC and Chang, CC and Hsu, SJ and Huang, YH and Hou, MC and Lee, FY}, title = {Hepatic encephalopathy: From novel pathogenesis mechanism to emerging treatments.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {87}, number = {3}, pages = {245-251}, doi = {10.1097/JCMA.0000000000001041}, pmid = {38109364}, issn = {1728-7731}, mesh = {Humans ; *Hepatic Encephalopathy/therapy/drug therapy ; Quality of Life ; Gastrointestinal Agents ; Lactulose/therapeutic use ; Rifaximin/therapeutic use ; }, abstract = {Hepatic encephalopathy (HE) is one of the major complications of liver disease and significantly affects the quality of life (QOL) of patients. HE is common and frequently relapses in cirrhotic patients. The management of HE is supportive, and precipitating conditions should be eliminated. Most drugs used to treat HE are conventional and include nonabsorbable disaccharides such as lactulose, and antibiotics such as rifaximin. However, their therapeutic efficacy is still suboptimal, and novel therapeutic agents are urgently needed. In addition, the optimal management and diagnosis of minimal HE/covert HE are under debate. In this review, we focus on novel pathogenetic mechanisms such as central nervous system clearance, and emerging therapeutic targets of HE, such as fecal material transplantation. We also discuss different classifications and etiologies of HE.}, }
@article {pmid38108689, year = {2023}, author = {Zhang, JY and Xiao, J and Xie, B and Barba, H and Boachie-Mensah, M and Shah, RN and Nadeem, U and Spedale, M and Dylla, N and Lin, H and Sidebottom, AM and D'Souza, M and Theriault, B and Sulakhe, D and Chang, EB and Skondra, D}, title = {Oral Metformin Inhibits Choroidal Neovascularization by Modulating the Gut-Retina Axis.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {64}, number = {15}, pages = {21}, pmid = {38108689}, issn = {1552-5783}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; }, mesh = {Male ; Female ; Animals ; Mice ; Angiogenesis Inhibitors ; RNA, Ribosomal, 16S ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; Retina ; *Choroidal Neovascularization/prevention &amp; control ; }, abstract = {PURPOSE: Emerging data indicate that metformin may prevent the development of age-related macular degeneration (AMD). Whereas the underlying mechanisms of metformin's anti-aging properties remain undetermined, one proposed avenue is the gut microbiome. Using the laser-induced choroidal neovascularization (CNV) model, we investigate the effects of oral metformin on CNV, retinal pigment epithelium (RPE)/choroid transcriptome, and gut microbiota.<br><br>METHODS: Specific pathogen free (SPF) male mice were treated via daily oral gavage of metformin 300&#xa0;mg/kg or vehicle. Male mice were selected to minimize sex-specific differences to laser induction and response to metformin. Laser-induced CNV size and macrophage/microglial infiltration were assessed by isolectin and Iba1 immunostaining. High-throughput RNA-seq of the RPE/choroid was performed using Illumina. Fecal pellets were analyzed for gut microbiota composition/pathways with 16S rRNA sequencing/shotgun metagenomics, as well as microbial-derived metabolites, including small-chain fatty acids and bile acids. Investigation was repeated in metformin-treated germ-free (GF) mice and antibiotic-treated/GF mice receiving fecal microbiota transplantation (FMT) from metformin-treated SPF mice.<br><br>RESULTS: Metformin treatment reduced CNV size (P < 0.01) and decreased Iba1+ macrophage/microglial infiltration (P < 0.005). One hundred forty-five differentially expressed genes were identified in the metformin-treated group (P < 0.05) with a downregulation in pro-angiogenic genes Tie1, Pgf, and Gata2. Furthermore, metformin altered the gut microbiome in favor of Bifidobacterium and Akkermansia, with a significant increase in fecal levels of butyrate, succinate, and cholic acid. Metformin did not suppress CNV in GF mice but colonization of microbiome-depleted mice with metformin-derived FMT suppressed CNV.<br><br>CONCLUSIONS: These data suggest that oral metformin suppresses CNV, the hallmark lesion of advanced neovascular AMD, via gut microbiome modulation.}, }
@article {pmid38108398, year = {2024}, author = {Elkrief, A and Waters, NR and Smith, N and Dai, A and Slingerland, J and Aleynick, N and Febles, B and Gogia, P and Socci, ND and Lumish, M and Giardina, PA and Chaft, JE and Eng, J and Motzer, RJ and Mendelsohn, RB and Markey, KA and Zhuang, M and Li, Y and Yang, Z and Hollmann, TJ and Rudin, CM and van den Brink, MRM and Shia, J and DeWolf, S and Schoenfeld, AJ and Hellmann, MD and Babady, NE and Faleck, DM and Peled, JU}, title = {Immune-Related Colitis Is Associated with Fecal Microbial Dysbiosis and Can Be Mitigated by Fecal Microbiota Transplantation.}, journal = {Cancer immunology research}, volume = {12}, number = {3}, pages = {308-321}, pmid = {38108398}, issn = {2326-6074}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; P50 CA254838/CA/NCI NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; Prospective Studies ; Dysbiosis/therapy/etiology ; *Gastrointestinal Microbiome ; Treatment Outcome ; *Colitis/therapy/complications ; *Biological Products ; }, abstract = {Colitis induced by treatment with immune-checkpoint inhibitors (ICI), termed irColitis, is a substantial cause of morbidity complicating cancer treatment. We hypothesized that abnormal fecal microbiome features would be present at the time of irColitis onset and that restoring the microbiome with fecal transplant from a healthy donor would mitigate disease severity. Herein, we present fecal microbiota profiles from 18 patients with irColitis from a single center, 5 of whom were treated with healthy-donor fecal microbial transplantation (FMT). Although fecal samples collected at onset of irColitis had comparable α-diversity to that of comparator groups with gastrointestinal symptoms, irColitis was characterized by fecal microbial dysbiosis. Abundances of Proteobacteria were associated with irColitis in multivariable analyses. Five patients with irColitis refractory to steroids and biologic anti-inflammatory agents received healthy-donor FMT, with initial clinical improvement in irColitis symptoms observed in four of five patients. Two subsequently exhibited recurrence of irColitis symptoms following courses of antibiotics. Both received a second "salvage" FMT that was, again, followed by clinical improvement of irColitis. In summary, we observed distinct microbial community changes that were present at the time of irColitis onset. FMT was followed by clinical improvements in several cases of steroid- and biologic-agent-refractory irColitis. Strategies to restore or prevent microbiome dysbiosis in the context of immunotherapy toxicities should be further explored in prospective clinical trials.}, }
@article {pmid38108213, year = {2024}, author = {Li, L and Liu, T and Shi, Y}, title = {Treatment of preterm brain injury via gut-microbiota-metabolite-brain axis.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {30}, number = {1}, pages = {e14556}, pmid = {38108213}, issn = {1755-5949}, support = {M1392//345 Talent Project of Shengjing Hospital/ ; M1415//345 Talent Project of Shengjing Hospital/ ; 2020JH1/10300001//Key R&amp;D Guidance Plan Project in Liaoning Province/ ; 82171709//National Natural Science Foundation of China/ ; 81801500//National Natural Science Foundation of China/ ; 2022-MS-207//Natural Science Foundation of Liaoning Province/ ; }, mesh = {Infant ; Infant, Newborn ; Humans ; Brain-Gut Axis ; Infant, Premature ; *Gastrointestinal Microbiome/physiology ; *Brain Injuries/therapy ; Brain ; }, abstract = {BACKGROUND: Brain injury in preterm infants potentially disrupts critical structural and functional connective networks in the brain. It is a major cause of neurological sequelae and developmental deficits in preterm infants. Interesting findings suggest that the gut microbiota (GM) and their metabolites contribute to the programming of the central nervous system (CNS) during developmental stages and may exert structural and functional effects throughout the lifespan.<br><br>AIM: To summarize the existing knowledge of the potential mechanisms related to immune, endocrine, neural, and blood-brain barrier (BBB) mediated by GM and its metabolites in neural development and function.<br><br>METHODS: We review the recent literature and included 150 articles to summarize the mechanisms through which GM and their metabolites work on the nervous system. Potential health benefits and challenges of relevant treatments are also discussed.<br><br>RESULTS: This review discusses the direct and indirect ways through which the GM may act on the nervous system. Treatment of preterm brain injury with GM or related derivatives, including probiotics, prebiotics, synbiotics, dietary interventions, and fecal transplants are also included.<br><br>CONCLUSION: This review summarizes mechanisms underlying microbiota-gut-brain axis and novel therapeutic opportunities for neurological sequelae in preterm infants. Optimizing the initial colonization and microbiota development in preterm infants may represent a novel therapy to promote brain development and reduce long-term sequelae.}, }
@article {pmid38103544, year = {2024}, author = {Lehmann, CJ and Dylla, NP and Odenwald, M and Nayak, R and Khalid, M and Boissiere, J and Cantoral, J and Adler, E and Stutz, MR and Dela Cruz, M and Moran, A and Lin, H and Ramaswamy, R and Sundararajan, A and Sidebottom, AM and Little, J and Pamer, EG and Aronsohn, A and Fung, J and Baker, TB and Kacha, A}, title = {Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {1}, pages = {117-130.e4}, doi = {10.1016/j.chom.2023.11.016}, pmid = {38103544}, issn = {1934-6069}, mesh = {Humans ; *Liver Transplantation/adverse effects ; Dysbiosis ; Feces ; Fatty Acids ; *Gastrointestinal Microbiome ; }, abstract = {Metabolites produced by the intestinal microbiome modulate mucosal immune defenses and optimize epithelial barrier function. Intestinal dysbiosis, including loss of intestinal microbiome diversity and expansion of antibiotic-resistant pathobionts, is accompanied by changes in fecal metabolite concentrations and increased incidence of systemic infection. Laboratory tests that quantify intestinal dysbiosis, however, have yet to be incorporated into clinical practice. We quantified fecal metabolites in 107 patients undergoing liver transplantation (LT) and correlated these with fecal microbiome compositions, pathobiont expansion, and postoperative infections. Consistent with experimental studies implicating microbiome-derived metabolites with host-mediated antimicrobial defenses, reduced fecal concentrations of short- and branched-chain fatty acids, secondary bile acids, and tryptophan metabolites correlate with compositional microbiome dysbiosis in LT patients and the relative risk of postoperative infection. Our findings demonstrate that fecal metabolite profiling can identify LT patients at increased risk of postoperative infection and may provide guideposts for microbiome-targeted therapies.}, }
@article {pmid38103514, year = {2024}, author = {Wu, Y and Feng, X and Li, M and Hu, Z and Zheng, Y and Chen, S and Luo, H}, title = {Gut microbiota associated with appetite suppression in high-temperature and high-humidity environments.}, journal = {EBioMedicine}, volume = {99}, number = {}, pages = {104918}, pmid = {38103514}, issn = {2352-3964}, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome ; Appetite ; Humidity ; Temperature ; Body Weight ; }, abstract = {BACKGROUND: Food is crucial for maintaining vital human and animal activities. Disorders in appetite control can lead to various metabolic disturbances. Alterations in the gut microbial composition can affect appetite and energy metabolism. While alterations in the gut microbiota have been observed in high-temperature and high-humidity (HTH) environments, the relationship between the gut microbiota during HTH and appetite remains unclear.<br><br>METHODS: We utilised an artificial climate box to mimic HTH environments, and established a faecal bacteria transplantation (FMT) mouse model. Mendelian randomisation (MR) analysis was used to further confirm the causal relationship between gut microbiota and appetite or appetite-related hormones.<br><br>FINDINGS: We found that, in the eighth week of exposure to HTH environments, mice showed a decrease in food intake and body weight, and there were significant changes in the intestinal microbiota compared to the control group. After FMT, we observed similar changes in food intake, body weight, and gut bacteria. Appetite-related hormones, including ghrelin, glucagon-like peptide-1, and insulin, were reduced in DH (mice exposed to HTH conditions) and DHF (FMT from mice exposed to HTH environments for 8 weeks), while the level of peptide YY initially increased and then decreased in DH and increased after FMT. Moreover, MR analysis further confirmed that these changes in the intestinal microbiota could affect appetite or appetite-related hormones.<br><br>INTERPRETATION: Together, our data suggest that the gut microbiota is closely associated with appetite suppression in HTH. These findings provide novel insights into the effects of HTH on appetite.<br><br>FUNDING: This work was supported by the National Natural Science Foundation of China and Guangzhou University of Chinese Medicine.}, }
@article {pmid38101472, year = {2024}, author = {Benech, N and Barbut, F and Fitzpatrick, F and Krutova, M and Davies, K and Druart, C and Cordaillat-Simmons, M and Heritage, J and Guery, B and Kuijper, E and , }, title = {Update on microbiota-derived therapies for recurrent Clostridioides difficile infections.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {4}, pages = {462-468}, doi = {10.1016/j.cmi.2023.12.007}, pmid = {38101472}, issn = {1469-0691}, mesh = {Humans ; *Clostridioides difficile ; Treatment Outcome ; Fecal Microbiota Transplantation ; *Clostridium Infections/microbiology ; *Microbiota ; Recurrence ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is the standard treatment for patients with multiple recurrent Clostridioides difficile infection (rCDI). Recently, new commercially developed human microbiota-derived medicinal products have been evaluated and Food and Drug Administration-approved with considerable differences in terms of composition, administration, and targeted populations.<br><br>OBJECTIVES: To review available data on the different microbiota-derived treatments at the stage of advanced clinical evaluation and research in rCDI in comparison with FMT.<br><br>SOURCES: Phase II or III trials evaluating a microbiota-derived medicinal product to prevent rCDI.<br><br>CONTENT: Two commercial microbiota-derived medicinal products are approved by the Food and Drug Administration: Rebyota (RBX2660 Ferring Pharmaceuticals, marketed in the United States) and VOWST (SER-109 -Seres Therapeutics, marketed in the United States), whereas VE303 (Vedanta Biosciences Inc) will be studied in phase III trial. RBX2660 and SER-109 are based on the processing of stools from healthy donors, whereas VE303 consists of a defined bacterial consortium originating from human stools and produced from clonal cell banks. All have proven efficacy to prevent rCDI compared with placebo in patients considered at high risk of recurrence. However, the heterogeneity of the inclusion criteria, and the time between each episode and CDI diagnostics makes direct comparison between trials difficult. The differences regarding the risk of recurrence between the treatment and placebo arms were lower than previously described for FMT (FMT: &#x394;&#xa0;=&#xa0;50.5%; RBX2660-phase III: &#x394;&#xa0;=&#xa0;13.1%; SER-109-phase III: &#x394;&#xa0;=&#xa0;28%; high-dose VE303-phase-II: &#x394;&#xa0;=&#xa0;31.7%). All treatments presented a good overall safety profile with mainly mild gastrointestinal symptoms.<br><br>IMPLICATIONS: Stool-derived products and bacterial consortia need to be clearly distinguished in terms of product characterization and their associated risks with specific long-term post-marketing evaluation similar to registries used for FMT. Their place in the therapeutic strategy for patients with rCDI requires further studies to determine the most appropriate patient population and administration route to prevent rCDI.}, }
@article {pmid38098663, year = {2023}, author = {Zheng, C and Zhong, Y and Xie, J and Wang, Z and Zhang, W and Pi, Y and Zhang, W and Liu, L and Luo, J and Xu, W}, title = {Bacteroides acidifaciens and its derived extracellular vesicles improve DSS-induced colitis.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1304232}, pmid = {38098663}, issn = {1664-302X}, abstract = {INTRODUCTION: "Probiotic therapy" to regulate gut microbiota and intervene in intestinal diseases such as inflammatory bowel disease (IBD) has become a research hotspot. Bacteroides acidifaciens, as a new generation of probiotics, has shown beneficial effects on various diseases.<br><br>METHODS: In this study, we utilized a mouse colitis model induced by dextran sodium sulfate (DSS) to investigate how B. acidifaciens positively affects IBD. We evaluated the effects ofB. acidifaciens, fecal microbiota transplantation, and bacterial extracellular vesicles (EVs) on DSS-induced colitis in mice. We monitored the phenotype of mouse colitis, detected serum inflammatory factors using ELISA, evaluated intestinal mucosal barrier function using Western blotting and tissue staining, evaluated gut microbiota using 16S rRNA sequencing, and analyzed differences in EVs protein composition derived from B. acidifaciens using proteomics to explore how B. acidifaciens has a positive impact on mouse colitis.<br><br>RESULTS: We confirmed that B. acidifaciens has a protective effect on colitis, including alleviating the colitis phenotype, reducing inflammatory response, and improving intestinal barrier function, accompanied by an increase in the relative abundance of B. acidifaciens and Ruminococcus callidus but a decrease in the relative abundance of B. fragilis. Further fecal bacterial transplantation or fecal filtrate transplantation confirmed the protective effect of eosinophil-regulated gut microbiota and metabolites on DSS-induced colitis. Finally, we validated that EVs derived from B. acidifaciens contain rich functional proteins that can contribute to the relief of colitis.<br><br>CONCLUSION: Therefore, B. acidifaciens and its derived EVs can alleviate DSS-induced colitis by reducing mucosal damage to colon tissue, reducing inflammatory response, promoting mucosal barrier repair, restoring gut microbiota diversity, and restoring gut microbiota balance in mice. The results of this study provide a theoretical basis for the preclinical application of the new generation of probiotics.}, }
@article {pmid38098430, year = {2024}, author = {Neubauer, J and Kaiser, A and Hohmann, S}, title = {[Gut Microbiota and Autism Spectrum Disorders: An Overview of Correlations and Potential Implications for Therapeutic Interventions].}, journal = {Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie}, volume = {52}, number = {3}, pages = {151-165}, doi = {10.1024/1422-4917/a000962}, pmid = {38098430}, issn = {1422-4917}, mesh = {*Autism Spectrum Disorder/therapy/microbiology/diagnosis/psychology ; Humans ; *Gastrointestinal Microbiome ; Child ; *Probiotics/therapeutic use ; *Brain-Gut Axis ; *Fecal Microbiota Transplantation ; *Prebiotics ; Dysbiosis ; Correlation of Data ; }, abstract = {Gut Microbiota and Autism Spectrum Disorders: An Overview of Correlations and Potential Implications for Therapeutic Interventions Abstract: At the beginning of research on microbiota, researchers focused mainly on the role of microbiota dysbiosis in the development of gastrointestinal diseases. However, over the last years, researchers have also identified correlations with other physical processes and neuropsychiatric diseases such as autism spectrum disorder. These correlations are believed to be at least partly mediated through the brain-gut-microbiome axis. An altered composition of microbiota in patients with autism spectrum disorder was detected compared to healthy controls. Today, the discussion centers around a possible systemic impact of the metabolites of some microbiota or microbiota-induced chronic inflammatory processes on the brain (mediated through the brain-gut-microbiome axis) as an underlying mechanism. Still, the specific underlying mechanisms remain largely unknown, so conclusions on therapeutic implications are difficult to determine. Here, we describe some promising approaches to improving autistic behavior through dietary changes, the use of prebiotics and probiotics, stool transplantation from healthy controls, and restricted absorbance of certain metabolites. We need further clinical studies of high quality to fully understand the pathophysiology of autism spectrum disorder and to improve diagnostic and therapeutic strategies.}, }
@article {pmid38096785, year = {2023}, author = {Rabot, S}, title = {tHIS way to cognitive development.}, journal = {Cell host &amp; microbe}, volume = {31}, number = {12}, pages = {1947-1949}, doi = {10.1016/j.chom.2023.11.018}, pmid = {38096785}, issn = {1934-6069}, mesh = {*Gastrointestinal Microbiome ; *Microbiota ; Fecal Microbiota Transplantation ; Cognition ; }, abstract = {The effect of the microbiota-gut-brain axis on cognitive development in infancy is increasingly being scrutinized. In this issue of Cell Host &amp; Microbe, Cerdó, Ruiz, and colleagues skillfully combine clinical and preclinical analyses, including a fecal transplantation experiment, to reveal associations between microbiota composition, cognitive scores, and histidine metabolism.}, }
@article {pmid38096022, year = {2023}, author = {Nita, AF and Chanpong, A and Nikaki, K and Rybak, A and Thapar, N and Borrelli, O}, title = {Recent advances in the treatment of gastrointestinal motility disorders in children.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {17}, number = {12}, pages = {1285-1300}, doi = {10.1080/17474124.2023.2295495}, pmid = {38096022}, issn = {1747-4132}, mesh = {Humans ; Child ; Quality of Life ; *Gastrointestinal Diseases/diagnosis/therapy ; *Esophageal Achalasia/diagnosis ; Constipation ; Gastrointestinal Motility ; }, abstract = {INTRODUCTION: Pediatric gastrointestinal motility disorders represent some of the most challenging clinical conditions with largely undefined pathogenetic pathways and therefore limited therapeutic options. Herein, we provide an overview of the recent advances in treatment options for these disorders and their clinical impact.<br><br>AREAS COVERED: PubMed and Medline databases were searched for relevant articles related to the treatment of achalasia, esophageal atresia, gastroparesis, PIPO and constipation published between 2017 and 2022. In this article, we review and summarize recent advances in management of gastrointestinal motility disorders in children with a particular focus on emerging therapies as well as novel diagnostic modalities that help guide their application or develop new, more targeted treatments.<br><br>EXPERT OPINION: Gastrointestinal motility disorders represent one of the most challenging conundrums in pediatric age and despite significant advances in investigative tools, the palette of treatment options remain limited. Overall, while pharmacological options have failed to bring a curative solution, recent advances in minimal invasive therapeutic and diagnostic techniques have emerged as potential keys to symptom and quality of life improvement, such as ENDOFLIP, POEM, cine-MRI, fecal microbiota transplantation.}, }
@article {pmid38095865, year = {2023}, author = {Pang, X and Chen, L and Xu, G}, title = {New Awareness of the Interplay Between the Gut Microbiota and Circadian Rhythms.}, journal = {Polish journal of microbiology}, volume = {72}, number = {4}, pages = {355-363}, pmid = {38095865}, issn = {2544-4646}, mesh = {*Gastrointestinal Microbiome ; Circadian Rhythm/physiology ; }, abstract = {Circadian rhythms influence various aspects of the biology and physiology of the host, such as food intake and sleep/wake cycles. In recent years, an increasing amount of genetic and epidemiological data has shown that the light/dark cycle is the main cue that regulates circadian rhythms. Other factors, including sleep/wake cycles and food intake, have necessary effects on the composition and rhythms of the gut microbiota. Interestingly, the gut microbiota can affect the circadian rhythm of hosts in turn through contact-dependent and contact-independent mechanisms. Furthermore, the gut microbiota has been shown to regulate the sleep/wake cycles through gut-brain-microbiota interaction. In addition to diabetes, the gut microbiota can also intervene in the progression of neuro- degenerative diseases through the gut-brain-microbiota interaction, and also in other diseases such as hypertension and rheumatoid arthritis, where it is thought to have a spare therapeutic potential. Even though fecal microbiota transplantation has good potential for treating many diseases, the risk of spreading intestinal pathogens should not be ignored.}, }
@article {pmid38094621, year = {2023}, author = {Li, SQ and Shen, Y and Zhang, J and Weng, CZ and Wu, SD and Jiang, W}, title = {Immune modulation of gut microbiota and its metabolites in chronic hepatitis B.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1285556}, pmid = {38094621}, issn = {1664-302X}, abstract = {The gut microbiota is a diverse ecosystem consisting of 100 trillion microbiomes. The interaction between the host's gut and distal organs profoundly impacts various functions such as metabolism, immunity, neurology, and nutrition within the human body. The liver, as the primary immune organ, plays a crucial role in maintaining immune homeostasis by receiving a significant influx of gut-derived components and toxins. Perturbations in gut microbiota homeostasis have been linked to a range of liver diseases. The advancements in sequencing technologies, such as 16S rRNA and metagenomics, have opened up new avenues for comprehending the intricate physiological interplay between the liver and the intestine. Metabolites produced by the gut microbiota function as signaling molecules and substrates, influencing both pathological and physiological processes. Establishing a comprehensive host-bacterium-metabolism axis holds tremendous potential for investigating the mechanisms underlying liver diseases. In this review, we have provided a summary of the detrimental effects of the gut-liver axis in chronic liver diseases, primarily focusing on hepatitis B virus-related chronic liver diseases. Moreover, we have explored the potential mechanisms through which the gut microbiota and its derivatives interact with liver immunity, with implications for future clinical therapies.}, }
@article {pmid38093327, year = {2023}, author = {Zhong, HJ and Wang, SQ and Zhang, RX and Zhuang, YP and Li, L and Yi, SZ and Li, Y and Wu, L and Ding, Y and Zhang, J and Xie, X and He, XX and Wu, Q}, title = {Supplementation with high-GABA-producing Lactobacillus plantarum L5 ameliorates essential tremor triggered by decreased gut bacteria-derived GABA.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {58}, pmid = {38093327}, issn = {2047-9158}, support = {2022B1111070006//Guangdong Science and Technology Department/ ; 2019QN01N107//Guangdong Science and Technology Department/ ; 2022GDASZH-2022020402-01//Guangdong Academy of Sciences/ ; }, mesh = {Humans ; Mice ; Animals ; *Lactobacillus plantarum/genetics ; *Essential Tremor ; Tremor ; Bacteria ; gamma-Aminobutyric Acid ; Dietary Supplements ; Mammals ; }, abstract = {BACKGROUND: The γ-aminobutyric acid (GABA) hypothesis posits a role of GABA deficiency in the central nervous system in the pathogenesis and progression of essential tremor (ET). However, the specific causative factor for GABA deficiency is not clear. The gut microbiota in mammals has recently been considered as a significant source of GABA. Furthermore, the GABA-based signals originating from the intestine can be transmitted to the brain through the "enteric nervous system-vagus nerve-brain" axis. However, the plausible contribution of gut microbiota to ET seems inspiring but remains obscure.<br><br>METHODS: Fecal samples from patients with ET and healthy controls were examined by metagenomic sequencing to compare the composition of gut microbiota and the expression of genes involved in GABA biosynthesis. The impact of gut microbiota on ET was explored through transplantation of fecal microbiota from patients with ET into the murine ET model. Lactic acid bacteria producing high amounts of GABA were identified through whole-genome sequencing and ultra-performance liquid chromatography-tandem mass spectrometry. Subsequently, mice were treated with the high-GABA-producing strain Lactobacillus plantarum L5. Tremor severity, behavioral tests, pro-inflammatory cytokines, GABA concentration, and gut microbiota composition were examined in these mice.<br><br>RESULTS: The gut microbiota of patients with ET demonstrated an impaired GABA-producing capacity and a reduced fecal GABA concentration. Transplantation of the gut microbiota from patients with ET induced an extension of tremor duration and impaired mobility in the murine model of ET. L5 exhibited an augmented GABA-producing capacity, with the De Man-Rogosa-Sharpe culture broth containing 262&#xa0;mg/l of GABA. In addition, administration of L5 significantly decreased the tremor severity and enhanced the movement capability and grasping ability of ET mice. In vivo mechanistic experiments indicated that L5 reshaped the gut microbial composition, supplemented the mucosa-associated microbiota with GABA-producing capacity, increased the GABA concentrations in the cerebellum, and diminished inflammation in the central nervous system.<br><br>CONCLUSIONS: These findings highlight that deficiency of GABA-producing gut microbes plays an essential role in the pathogenesis of ET and that L5 is a promising candidate for treating ET.}, }
@article {pmid38090578, year = {2023}, author = {Liu, W and Jiang, H and Liu, X and Zheng, Y and Liu, Y and Pan, F and Yu, F and Li, Z and Gu, M and Du, Q and Li, X and Zhang, H and Han, D}, title = {Altered intestinal microbiota enhances adenoid hypertrophy by disrupting the immune balance.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1277351}, pmid = {38090578}, issn = {1664-3224}, mesh = {Child ; Humans ; Animals ; Mice ; *Gastrointestinal Microbiome/physiology ; *Adenoids ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Hypertrophy ; Bacteroides/genetics ; }, abstract = {INTRODUCTION: Adenoid hypertrophy (AH) is a common upper respiratory disorder in children. Disturbances of gut microbiota have been implicated in AH. However, the interplay of alteration of gut microbiome and enlarged adenoids remains elusive.<br><br>METHODS: 119 AH children and 100 healthy controls were recruited, and microbiome profiling of fecal samples in participants was performed using 16S rRNA gene sequencing. Fecal microbiome transplantation (FMT) was conducted to verify the effects of gut microbiota on immune response in mice.<br><br>RESULTS: In AH individuals, only a slight decrease of diversity in bacterial community was found, while significant changes of microbial composition were observed between these two groups. Compared with HCs, decreased abundances of Akkermansia, Oscillospiraceae and Eubacterium coprostanoligenes genera and increased abundances of Bacteroides, Faecalibacterium, Ruminococcus gnavus genera were revealed in AH patients. The abundance of Bacteroides remained stable with age in AH children. Notably, a microbial marker panel of 8 OTUs were identified, which discriminated AH from HC individuals with an area under the curve (AUC) of 0.9851 in the discovery set, and verified in the geographically different validation set, achieving an AUC of 0.9782. Furthermore, transfer of mice with fecal microbiota from AH patients dramatically reduced the proportion of Treg subsets within peripheral blood and nasal-associated lymphoid tissue (NALT) and promoted the expansion of Th2 cells in NALT.<br><br>CONCLUSION: These findings highlight the effect of the altered gut microbiota in the AH pathogenesis.}, }
@article {pmid38088972, year = {2023}, author = {Fang, H and Yao, T and Li, W and Pan, N and Xu, H and Zhao, Q and Su, Y and Xiong, K and Wang, J}, title = {Efficacy and safety of fecal microbiota transplantation for chronic insomnia in adults: a real world study.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1299816}, pmid = {38088972}, issn = {1664-302X}, abstract = {OBJECTIVE: To assess the efficacy and safety of fecal microbiota transplantation (FMT) for adult chronic insomnia.<br><br>METHODS: Patients treated with FMT for chronic diseases were divided into chronic insomnia and non-insomnia group. The primary endpoint was the efficacy of FMT for insomnia 4&#x2009;weeks after treatment, the secondary endpoints included the impacts of FMT on anxiety, depression, health-related quality of life, gut microbiota, and adverse events associated with FMT. Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) were utilized to assess the efficacy of FMT on insomnia, self-rating anxiety/depression scale [Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS)] was employed to evaluate anxiety and depression. Quality of life was evaluated by SF-36. 16S rRNA sequencing was employed to analyze the gut microbiota and correlation analysis was performed.<br><br>RESULTS: Forty patients met the inclusion criteria and seven were excluded. 33 patients were enrolled and stratified into chronic insomnia group (N&#x2009;=&#x2009;17) and non-insomnia group (N&#x2009;=&#x2009;16). Compared to baseline, FMT significantly ameliorated the ISI (17.31&#x2009;&#xb1;&#x2009;5.12 vs. 5.38&#x2009;&#xb1;&#x2009;5.99), PSQI (14.56&#x2009;&#xb1;&#x2009;2.13 vs. 6.63&#x2009;&#xb1;&#x2009;4.67), SAS (54.25&#x2009;&#xb1;&#x2009;8.90 vs. 43.68&#x2009;&#xb1;&#x2009;10.64) and SDS (57.43&#x2009;&#xb1;&#x2009;10.96 vs. 50.68&#x2009;&#xb1;&#x2009;15.27) score and quality of life of chronic insomnia patients. 76.47% (13/17) of insomnia patients achieved the primary endpoints. In chronic insomnia patients, the relative abundance of Eggerthella marked enhanced at baseline, while the relative abundance of Lactobacillus, Bifidobacterium, Turicibacter, Anaerostipes, and Eisenbergiella significantly increased after FMT treatment, the latter positive correlated with the efficacy of FMT. Encouragingly, FMT also improved the sleep quality of non-insomnia patients.<br><br>CONCLUSION: Eggerthella may potentially serve as a distinctive genus associated with chronic insomnia. FMT maybe a novel treatment option for adults with chronic insomnia and provide an alternative to traditional treatments for insomnia. The effects were positive correlated with the augmentation of probiotics, such as Bifidobacterium, Lactobacillus, Turicibacter, and Fusobacterium.}, }
@article {pmid38088959, year = {2023}, author = {Deng, H and Yu, Y and Sha, Q and Sun, W and Liang, L and Ren, F and Ji, H and Shen, X and Fan, X}, title = {Construction of antibiotic-induced depression mice model and the function of intestinal microbiota.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1093486}, pmid = {38088959}, issn = {1664-302X}, abstract = {Many research studies focus on intestinal microbiota-related depression induced by the usage of antibiotics, but the use of antibiotics is fairly different. To construct an effective antibiotic-induced depression mice model and explore the effect of intestinal microbiota in antibiotic-induced depression, we used several kinds of antibiotic mixtures to induce mice depression and used depression-related behavioral tests and neurobiological factors to evaluate the construction of the antibiotic-induced depression mice model. SPSS statistical software was used to analyze the above data, and the optimal model was selected according to the stability of the results and the simplicity of the modeling methods. Metagenomic analysis and fecal microbiota transplantation (FMT) of intestinal microbiota from antibiotic-induced depression mice were performed to analyze the effect of intestinal microbiota. The results showed that antibiotic mixture A (1.25 μg/mL natamycin, 5 mg/mL neomycin sulfate, and 5 mg/mL bacitracin), antibiotic mixture B (24 mg/mL bacitracin, 24 mg/mL neomycin sulfate, 9.6 mg/mL ampicillin, 4.8 mg/mL meropenem, and 1.47 mg/mL vancomycin), and antibiotic solution D (only containing 5 mg/mL neomycin sulfate) could induce depression-like behavior in mice. By using these antibiotics, the concentrations of norepinephrine (NE), 5-hydroxytryptamine (5-HT), and brain-derived neurotrophic factor (BDNF) in mice hippocampus and prefrontal cortex tissues were significantly decreased. All the above results were consistent with those of chronic unpredictable mild stress (CUMS) depression mice. The FMT results showed that fecal microbiota from antibiotic-induced depressed mice transplanted into normal mice (8 weeks-old male C57BL/6J SPF mice) also could induce depression-like behavior and cause similar changes in neurobiological factors. Metagenomic analysis showed that the community structure of microbiota in the intestinal tract of antibiotic-induced depression mice was significantly different from that in control mice, the intestinal microbiota species diversity in antibiotic-induced depression mice was lower, the lipoic acid metabolism pathway was significantly activated, and the abundance of functional gene lipA was explicitly increased. Quantitative real-time PCR (qPCR) further verified the abundance of enriched bacteria in the intestinal microbiota of antibiotic-induced depression mice. In summary, the specific antibiotic mixtures can induce depression by causing changes in intestinal microbiota in mice. Antibiotic-induced depressed mice show differences in intestinal microbiota abundance, high enrichment of the unique metabolic pathway, and the functional gene.}, }
@article {pmid38088183, year = {2024}, author = {Chalif, J and Wang, H and Spakowicz, D and Quick, A and Arthur, EK and O'Malley, D and Chambers, LM}, title = {The microbiome and gynecologic cancer: cellular mechanisms and clinical applications.}, journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society}, volume = {34}, number = {2}, pages = {317-327}, doi = {10.1136/ijgc-2023-004894}, pmid = {38088183}, issn = {1525-1438}, mesh = {Humans ; Female ; *Genital Neoplasms, Female/microbiology/therapy ; Microbiota/physiology ; Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; }, abstract = {The microbiome plays a vital function in maintaining human health and homeostasis. Each microbiota has unique characteristics, including those of the gastrointestinal and female reproductive tract. Dysbiosis, or alterations to the composition of the microbial communities, impacts the microbiota-host relationship and is linked to diseases, including cancer. In addition, studies have demonstrated that the microbiota can contribute to a pro-carcinogenic state through altered host immunologic response, modulation of cell proliferation, signaling, gene expression, and dysregulated metabolism of nutrients and hormones.In recent years, the microbiota of the gut and female reproductive tracts have been linked to many diseases, including gynecologic cancers. Numerous pre-clinical and clinical studies have demonstrated that specific bacteria or microbial communities may contribute to the development of gynecologic cancers. Further, the microbiota may also impact the toxicity and efficacy of cancer therapies, including chemotherapy, immunotherapy, and radiation therapy in women with gynecologic malignancies. The microbiota is highly dynamic and may be altered through various mechanisms, including diet, exercise, medications, and fecal microbiota transplantation. This review provides an overview of the current literature detailing the relationship between gynecologic cancers and the microbiota of the female reproductive and gastrointestinal tracts, focusing on mechanisms of carcinogenesis and strategies for modulating the microbiota for cancer prevention and treatment. Advancing our understanding of the complex relationship between the microbiota and gynecologic cancer will provide a novel approach for prevention and therapeutic modulation in the future.}, }
@article {pmid38088063, year = {2024}, author = {Nohesara, S and Abdolmaleky, HM and Thiagalingam, S and Zhou, JR}, title = {Gut microbiota defined epigenomes of Alzheimer's and Parkinson's diseases reveal novel targets for therapy.}, journal = {Epigenomics}, volume = {16}, number = {1}, pages = {57-77}, pmid = {38088063}, issn = {1750-192X}, support = {R01 CA138509/CA/NCI NIH HHS/United States ; R21 CA165707/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Parkinson Disease/genetics/therapy ; *Alzheimer Disease/genetics/therapy/metabolism ; Brain/metabolism ; Epigenome ; }, abstract = {The origins of Alzheimer's disease (AD) and Parkinson's disease (PD) involve genetic mutations, epigenetic changes, neurotoxin exposure and gut microbiota dysregulation. The gut microbiota's dynamic composition and its metabolites influence intestinal and blood-brain barrier integrity, contributing to AD and PD development. This review explores protein misfolding, aggregation and epigenetic links in AD and PD pathogenesis. It also highlights the role of a leaky gut and the microbiota-gut-brain axis in promoting these diseases through inflammation-induced epigenetic alterations. In addition, we investigate the potential of diet, probiotics and microbiota transplantation for preventing and treating AD and PD via epigenetic modifications, along with a discussion related to current challenges and future considerations. These approaches offer promise for translating research findings into practical clinical applications.}, }
@article {pmid38087767, year = {2024}, author = {Tabata, K and Ikarashi, N and Shinozaki, Y and Yoshida, R and Kon, R and Sakai, H and Hosoe, T and Kamei, J}, title = {Effect of the gut microbiota on the expression of genes that are important for maintaining skin function: Analysis using aged mice.}, journal = {The Journal of dermatology}, volume = {51}, number = {3}, pages = {419-428}, doi = {10.1111/1346-8138.17062}, pmid = {38087767}, issn = {1346-8138}, support = {19K08783//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/genetics ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiota changes greatly at the onset of disease, and the importance of intestinal bacteria has been highlighted. The gut microbiota also changes greatly with aging. Aging causes skin dryness, but it is not known how changes in the gut microbiota with aging affects the expression of genes that are important for maintaining skin function. In this study, we investigated how age-related changes in gut microbiota affect the expression of genes that regulate skin function. The gut microbiotas from young mice and aged mice were transplanted into germ-free mice (fecal microbiota transplantation [FMT]). These recipient mice were designated FMT-young mice and FMT-old mice respectively, and the expression levels of genes important for maintaining skin function were analyzed. The dermal water content was significantly lower in old mice than that in young mice, indicating dry skin. The gut microbiota significantly differed between old mice and young mice. The water channel aquaporin-3 (Aqp3) expression level in the skin of FMT-old mice was significantly higher than that in FMT-young mice. In addition, among the genes that play an important role in maintaining skin function, the expression levels of those encoding ceramide-degrading enzyme, ceramide synthase, hyaluronic acid-degrading enzyme, and Type I collagen were also significantly higher in FMT-old mice than in FMT-young mice. It was revealed that the gut microbiota, which changes with age, regulates the expression levels of genes related to skin function, including AQP3.}, }
@article {pmid38087724, year = {2024}, author = {Pakmehr, A and Mousavi, SM and Ejtahed, HS and Hoseini-Tavassol, Z and Siadat, SD and Hasani-Ranjbar, S and Larijani, B}, title = {The Effect of Fecal Microbiota Transplantation on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis.}, journal = {Clinical therapeutics}, volume = {46}, number = {2}, pages = {e87-e100}, doi = {10.1016/j.clinthera.2023.11.015}, pmid = {38087724}, issn = {1879-114X}, mesh = {Humans ; *Cardiovascular Diseases/prevention &amp; control ; Dysbiosis ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Insulin Resistance ; }, abstract = {PURPOSE: Cardiometabolic disease (CMD) is increasing along with its predisposing factors and adverse consequences. As gut microbiota dysbiosis is established in these patients, fecal microbiota transplantation (FMT), which alters the bacterial composition of the intestine, supposedly can help improve cardiometabolic disturbances. We conducted a systematic review and meta-analysis evaluating the impact of FMT on the cardiometabolic parameters and gut microbiota composition of patients experiencing at least one cardiometabolic issue.<br><br>METHODS: Eligible studies were searched through the PubMed, Web of Science, and Scopus databases until December 2022. The initial search results underwent duplication removal and screening until each included study was scanned for intended data. The Cochrane risk of bias tool was used to evaluate the methodologic accuracy of studies and the random effects model was used for conducting the meta-analysis.<br><br>FINDINGS: Eighteen of the original 2414 articles from the literature search were entered into the systematic review; of these, 11 were included in the meta-analysis. Insulin showed a significant decrease by 24.7 pmol/L (weighted mean difference [WMD], -24.77; 95% CI, -48.704 to -0.848) after short-term follow-up, and HDL increased by 0.1 mmol/l(WMD, 0.106; 95% CI, 0.027 to 0.184) and 0.12 mmol/l(WMD, 0.120; 95% CI, 0.003 to 0.237) in those using a capsule deliver mode and in short-term follow-up, respectively. No significant changes were seen in other lipid profiles, blood glucose, insulin resistance, or anthropometric indices. In addition, multiple studies reported gut microbiota alterations after the intervention, including an increase in butyrate-producing species.<br><br>IMPLICATIONS: Although some articles reported the beneficial effects of FMT on metabolic parameters, we failed to find a clinically significant alteration. Also, information regarding proper donors and the best method to induce FMT have not yet been sufficiently investigated, which should be considered along with means to prevent potential damages. PROSPERO identifier: CRD42022380705.}, }
@article {pmid38087373, year = {2023}, author = {Yang, J and Liu, S and Zhao, Q and Li, X and Jiang, K}, title = {Gut microbiota-related metabolite alpha-linolenic acid mitigates intestinal inflammation induced by oral infection with Toxoplasma gondii.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {273}, pmid = {38087373}, issn = {2049-2618}, support = {202301BD070001-069//Joint Special Project of Agricultural Basic Research in Yunnan/ ; 202301AU070109//Yunnan Fundamental Research Projects/ ; }, mesh = {Mice ; Animals ; *Toxoplasma ; alpha-Linolenic Acid ; *Gastrointestinal Microbiome/physiology ; RNA, Ribosomal, 16S/genetics ; Myeloid Differentiation Factor 88 ; NF-kappa B ; *Toxoplasmosis/microbiology ; *Communicable Diseases ; *Colitis ; Cytokines ; Bacteria ; Inflammation/microbiology ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Oral infection with cysts is the main transmission route of Toxoplasma gondii (T. gondii), which leads to lethal intestinal inflammation. It has been widely recognized that T. gondii infection alters the composition and metabolism of the gut microbiota, thereby affecting the progression of toxoplasmosis. However, the potential mechanisms remain unclear. In our previous study, there was a decrease in the severity of toxoplasmosis after T. gondii α-amylase (α-AMY) was knocked out. Here, we established mouse models of ME49 and Δα-amy cyst infection and then took advantage of 16S rRNA gene sequencing and metabolomics analysis to identify specific gut microbiota-related metabolites that mitigate T. gondii-induced intestinal inflammation and analyzed the underlying mechanism.<br><br>RESULTS: There were significant differences in the intestinal inflammation between ME49 cyst- and &#x394;&#x3b1;-amy cyst-infected mice, and transferring feces from mice infected with &#x394;&#x3b1;-amy cysts into antibiotic-treated mice mitigated colitis caused by T. gondii infection. 16S rRNA gene sequencing showed that the relative abundances of gut bacteria, such as Lactobacillus and Bacteroides, Bifidobacterium, [Prevotella], Paraprevotella and Macellibacteroides, were enriched in mice challenged with &#x394;&#x3b1;-amy cysts. Spearman correlation analysis between gut microbiota and metabolites indicated that some fatty acids, including azelaic acid, suberic acid, alpha-linolenic acid (ALA), and citramalic acid, were highly positively correlated with the identified bacterial genera. Both oral administration of ALA and fecal microbiota transplantation (FMT) decreased the expression of pro-inflammatory cytokines and restrained the MyD88/NF-&#x3ba;B pathway, which mitigated colitis and ultimately improved host survival. Furthermore, transferring feces from mice treated with ALA reshaped the colonization of beneficial bacteria, such as Enterobacteriaceae, Proteobacteria, Shigella, Lactobacillus, and Enterococcus.<br><br>CONCLUSIONS: The present findings demonstrate that the host gut microbiota is closely associated with the severity of T. gondii infection. We provide the first evidence that ALA can alleviate T. gondii-induced colitis by improving the dysregulation of the host gut microbiota and suppressing the production of pro-inflammatory cytokines via the MyD88/NF-&#x3ba;B pathway. Our study provides new insight into the medical application of ALA for the treatment of lethal intestinal inflammation caused by Toxoplasma infection. Video Abstract.}, }
@article {pmid38087164, year = {2024}, author = {Chen, S and Jiao, Y and Han, C and Li, Y and Zou, W and Liu, J}, title = {Drug-Resistant Epilepsy and Gut-Brain Axis: an Overview of a New Strategy for Treatment.}, journal = {Molecular neurobiology}, volume = {61}, number = {12}, pages = {10023-10040}, pmid = {38087164}, issn = {1559-1182}, support = {2021JH2/10300135//Liaoning Directed project for planning of science and technology/ ; 2112006//Dalian Science and Technology Innovation Fund/ ; 2021RQ028//Dalian High-Level Talent Innovation Program/ ; XLYC1902031//Liaoning Province Excellent Talent Program Project/ ; 2022RG18//Dalian High-level Talent Team Project/ ; CMR-20161129-1003//National Health and Family Planning Commission and Food and Drug Administration/ ; }, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; *Brain-Gut Axis/physiology ; *Drug Resistant Epilepsy/therapy/microbiology ; Diet, Ketogenic ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation/methods ; }, abstract = {Drug-resistant epilepsy (DRE), also known as intractable epilepsy or refractory epilepsy, is a disease state with long-term poorly controlled seizures attack. Without effective treatment, patients are at an elevated risk of injury, premature death, mental disorders, and poor quality of life, increasing the need for a fresh perspective on the etiology and treatment of DRE. The gut is known to harbor a wide variety of microorganisms that can regulate the host's response to exogenous signals and participate in various physiological and pathological processes in the human body. Interestingly, emerging evidence has uncovered the changes in gut microbiota in patients with epilepsy, particularly those with DRE. In addition, both dietary interventions and specific antibiotic therapy have been proven to be effective in restoring the microecological environment and, more importantly, reducing seizures. Here, we reviewed recent studies on DRE and the involvement of gut microbiota in it, describing changes in the gut microflora composition in patients with DRE and corresponding animal models. Furthermore, the influence of the ketogenic diet, probiotics, fecal microbiota transplantation (FMT), and antibiotics as microbiome-related factors on seizure control and its possible mechanisms are broadly discussed. Finally, we highlighted the significance of gut microbiome in DRE, in order to provide a new prospect for early identification and individualized treatment of patients with DRE.}, }
@article {pmid38087159, year = {2023}, author = {Wu, D and Xiong, W and Ma, S and Luo, J and Ye, H and Huang, S and Li, F and Xiang, X and Chen, Q and Gao, B and Deng, J and Yin, Y and Tan, C}, title = {Konjac flour-mediated gut microbiota alleviates insulin resistance and improves placental angiogenesis of obese sows.}, journal = {AMB Express}, volume = {13}, number = {1}, pages = {143}, pmid = {38087159}, issn = {2191-0855}, support = {2021A1515012116//Natural science foundation of guangdong province/ ; 32272895//national natural science foundation china/ ; 32172744//national natural science foundation china/ ; }, abstract = {Our previous study revealed that dietary konjac flour (KF) could remodel gut microbiota and improve reproductive performance of sows, but its underlying mechanisms remain unclear. This experiment aimed to investigate how dietary KF improves reproductive performance of obese sows. Here, 60 sows were assigned into three groups according to their backfat thickness: normal backfat sows fed with control diet (CON-N), high backfat sows fed with control diet (CON-H) and high backfat sows fed with KF inclusion diet (KF-H). The characteristics of sows and piglets were recorded. Next, fecal microbiota transplantation (FMT) was performed on female mice, followed by recording the characteristics of female mice. The results showed that compared with CON-H group, KF-H group showed downtrend in stillbirth rate (P = 0.07), an increase in placental efficiency (P < 0.01) and average piglet weight (P < 0.01); coupled with a decrease in the values of homeostasis model assessment-insulin resistance (P < 0.01); as well as an increase in placental vascular density and protein expression of angiogenesis markers (P < 0.01). As expected, sows fed KF diets had improved abundance and diversity of gut microbiota. More importantly, compared with CON-H(FMT) group, KF-H(FMT) group showed improvement in reproductive performance and insulin sensitivity (P < 0.05), as well as an increase in placental labyrinth zone and protein expression of angiogenesis markers (P < 0.05). Furthermore, we found a content increase (P < 0.05) of SCFAs in both KF-H group sow and KF-H (FMT) group mice. Overall, KF supplementation could alleviate insulin resistance, promote placental angiogenesis, and ultimately improve the reproductive performance of sows via gut microbiota remodeling.}, }
@article {pmid38087070, year = {2024}, author = {Corriero, A and Giglio, M and Inchingolo, F and Moschetta, A and Varrassi, G and Puntillo, F}, title = {Gut Microbiota Modulation and Its Implications on Neuropathic Pain: A Comprehensive Literature Review.}, journal = {Pain and therapy}, volume = {13}, number = {1}, pages = {33-51}, pmid = {38087070}, issn = {2193-8237}, abstract = {Neuropathic pain (NP) is a chronic pain disorder arising from somatosensory nervous system impairment. Extensive evidence supports the notion that the gut microbiota (GM) is crucial in maintaining human health by performing vital tasks. At the same time, its disruption has been linked to the emergence and advancement of an expanding range of disorders, including NP, in which GM could play a role in its pathophysiology. The crosstalk between the nervous system and GM happens through immune mediators, metabolites, and nervous structures and involves both central and peripheral nervous systems. This literature review aims to thoroughly investigate the function of modulating GM in the treatment of NP. It will achieve this by integrating existing knowledge, identifying underlying mechanisms, and evaluating the possible clinical consequences of exploiting the gut-brain axis. We will cover the main therapeutic applications of the described GM-modulators, such as probiotics, faecal microbiota transplantation, dietary supplements and emotional support, to the main kinds of NP in which any evidence, even if only pre-clinical, has been unravelled in recent years. The explored NP areas include chemotherapy-induced peripheral neuropathy, diabetic neuropathy, trauma-induced neuropathic pain, trigeminal neuralgia, postherpetic neuralgia and low back pain.}, }
@article {pmid38084725, year = {2024}, author = {El-Salhy, M and Gilja, OH and Hatlebakk, JG}, title = {Increasing the transplant dose and repeating faecal microbiota transplantation results in the responses of male patients with IBS reaching those of females.}, journal = {Scandinavian journal of gastroenterology}, volume = {59}, number = {4}, pages = {391-400}, doi = {10.1080/00365521.2023.2292479}, pmid = {38084725}, issn = {1502-7708}, mesh = {Humans ; Male ; Female ; Fecal Microbiota Transplantation/methods ; *Irritable Bowel Syndrome/diagnosis ; Quality of Life ; RNA, Ribosomal, 16S ; *Gastrointestinal Microbiome ; Feces/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) performed with a proper protocol is a safe treatment for IBS that has high efficacy and durable effects. Females have been reported to respond better than males to FMT. The present study aimed at determining whether increasing the transplant dose or repeating FMT improve the responses of males to FMT.<br><br>METHODS: This study included 186 IBS patients (131 females and 55 males) who were randomized at a 1:1:1 ratio to receive 90&#x2009;g of donor faeces once into the large intestine, once into the small intestine or twice into the small intestine. Patients completed five questionnaires that assessed their symptoms and quality of life, and provided faecal samples at baseline and at 3, 6 and 12&#x2009;months after FMT. The faecal bacterial profile and dysbiosis index were determined using 16S rRNA gene PCR DNA amplification covering variable genes V3-V9.<br><br>RESULTS: The response rates to FMT at all observation times did not differ significantly between females and males regardless of the transplant administration route or whether it was repeated. Faecal Alistipes levels were higher in females than in males at baseline and increased in both females and males after FMT. In the repeated group, the Alistipes levels did not differ between females and males after FMT.<br><br>CONCLUSIONS: Increasing the transplant dose and repeating FMT results in the responses of male IBS patients to FMT reaching those of females regardless of the administration route. Alistipes spp. levels appear to play a role in this improvement.www.clinicaltrials.gov (NCT04236843).}, }
@article {pmid38079533, year = {2024}, author = {He, X and Gao, X and Hong, Y and Zhong, J and Li, Y and Zhu, W and Ma, J and Huang, W and Li, Y and Li, Y and Wang, H and Liu, Z and Bao, Y and Pan, L and Zheng, N and Sheng, L and Li, H}, title = {High Fat Diet and High Sucrose Intake Divergently Induce Dysregulation of Glucose Homeostasis through Distinct Gut Microbiota-Derived Bile Acid Metabolism in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {1}, pages = {230-244}, doi = {10.1021/acs.jafc.3c02909}, pmid = {38079533}, issn = {1520-5118}, mesh = {Animals ; Mice ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 2 ; Sucrose ; Lipid Metabolism ; Glucose/pharmacology ; Homeostasis ; Bile Acids and Salts/pharmacology ; Mice, Inbred C57BL ; }, abstract = {A high calorie diet such as excessive fat and sucrose intake is always accompanied by impaired glucose homeostasis such as T2DM (type 2 diabetes mellitus). However, it remains unclear how fat and sucrose individually affect host glucose metabolism. In this study, mice were fed with high fat diet (HFD) or 30% sucrose in drinking water (HSD) for 24 weeks, and glucose metabolism, gut microbiota composition, as well as bile acid (BA) profile were investigated. In addition, the functional changes of HFD or HSD-induced gut microbiota were further verified by fecal microbiota transplantation (FMT) and ex vivo culture of gut bacteria with BAs. Our results showed that both HFD and HSD caused dysregulated lipid metabolism, while HFD feeding had a more severe effect on impaired glucose homeostasis, accompanied by reduced hyocholic acid (HCA) levels in all studied tissues. Meanwhile, HFD had a more dramatic influence on composition and function of gut microbiota based on α diversity indices, β diversity analysis, as well as the abundance of secondary BA producers than HSD. In addition, the phenotypes of impaired glucose homeostasis and less formation of HCA caused by HFD can be transferred to recipient mice by FMT. Ex vivo culture with gut bacteria and BAs revealed HFD-altered gut bacteria produced less HCA than HSD, which might closely associate with reduced relative abundance of C7 epimerase-coding bacteria g_norank/unclassified_f_Eggerthellaceae and bile salt hydrolase-producing bacteria Lactobacillus and Bifidobacterium in HFD group. Our findings revealed that the divergent effects of different high-calorie diets on glucose metabolism may be due to the gut microbiota-mediated generation and metabolism of BAs, highlighting the importance of dietary management in T2DM.}, }
@article {pmid38076985, year = {2023}, author = {Jain, R and Hadjigeorgiou, A and Harkos, C and Mishra, A and Morad, G and Johnson, S and Ajami, N and Wargo, J and Munn, L and Stylianopoulos, T}, title = {Dissecting the Impact of the Gut Microbiome on Cancer Immunotherapy.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38076985}, issn = {2693-5015}, support = {F32 CA260769/CA/NCI NIH HHS/United States ; R01 NS118929/NS/NINDS NIH HHS/United States ; U01 CA224348/CA/NCI NIH HHS/United States ; R01 CA259253/CA/NCI NIH HHS/United States ; R21 EB031982/EB/NIBIB NIH HHS/United States ; R35 CA197743/CA/NCI NIH HHS/United States ; R01 CA208205/CA/NCI NIH HHS/United States ; R01 CA247441/CA/NCI NIH HHS/United States ; R01 CA219896/CA/NCI NIH HHS/United States ; U01 CA261842/CA/NCI NIH HHS/United States ; }, abstract = {The gut microbiome has emerged as a key regulator of response to cancer immunotherapy. However, there is a gap in our understanding of the underlying mechanisms by which the microbiome influences immunotherapy. To this end, we developed a mathematical model based on i) gut microbiome data derived from preclinical studies on melanomas after fecal microbiota transplant, ii) mechanistic modeling of antitumor immune response, and iii) robust association analysis of murine and human microbiome profiles with model-predicted immune profiles. Using our model, we could distill the complexity of these murine and human studies on microbiome modulation in terms of just two model parameters: the activation and killing rate constants of immune cells. We further investigated associations between specific bacterial taxonomies and antitumor immunity and immunotherapy efficacy. This model can guide the design of studies to refine and validate mechanistic links between the microbiome and immune system.}, }
@article {pmid38075901, year = {2023}, author = {Li, Y and Zhang, Y and Luo, X and Meng, Y and Zhong, Z and Zheng, H and Yang, Y}, title = {The fecal microbiota from children with autism impact gut metabolism and learning and memory abilities of honeybees.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1278162}, pmid = {38075901}, issn = {1664-302X}, abstract = {Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders, with an increasing incidence. Gastrointestinal symptoms are common comorbidities of ASD. The gut microbiota composition of children with autism is distinct from that of typical developmental (TD) children, suggesting that the gut microbiota probably influences on hosts via the microbiota-gut-brain axis. However, the relationship between intestinal dysbiosis and host brain function remains unclear. In this study, we creatively developed a honeybee model and investigated the potential effects of fecal microbiota on hosts. Fecal microbiota from children with autism and TD children were transplanted into microbiota-free honeybees (Apis mellifera), resulting in induced ASD-fecal microbiota transplantation (FMT) honeybees (A-BEE group) and TD-FMT honeybees (T-BEE group), respectively. We found that cognitive abilities of honeybees in the A-BEE group were significantly impaired in olfactory proboscis extension response conditioning. Metagenomics was used to evaluate fecal microbiota colonization, revealing several differential species responsible for altered tryptophan metabolism and taurine metabolism within the bee gut, including Bacteroides dorei, Bacteroides fragilis, Lactobacillus gasseri, and Lactobacillus paragasseri. Furthermore, fecal microbiota from children with autism downregulated brain genes involved in neural signaling and synaptic transmission within honeybees. Notably, differentially spliced genes observed within brains of honeybees from the A-BEE group largely overlapped with those identified in human diagnosed with autism via SFARI and SPARK gene sets. These differentially spliced genes were also enriched within pathways related to neural synaptic transmission. Our findings provide novel insights into the pivotal role of the human gut microbiota, which may contribute to neurological processes in honeybees. Additionally, we present a few research sources on gut-brain connections in ASD.}, }
@article {pmid38075897, year = {2023}, author = {Bonnet, M and Eckert, C and Tournebize, R}, title = {Decolonization of asymptomatic carriage of multi-drug resistant bacteria by bacteriophages?.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1266416}, pmid = {38075897}, issn = {1664-302X}, abstract = {Antimicrobial resistance is a major threat to human and animal health and accounted for up to 4.5 million deaths worldwide in 2019. Asymptomatic colonization of the digestive tract by multidrug resistant (multi-resistant) bacteria such as extended-spectrum beta-lactamase-, or carbapenemase- producing Enterobacterales is (i) a risk factor for infection by these multi-resistant bacteria, (ii) a risk factor of dissemination of these multi-resistant bacteria among patients and in the community, and (iii) allows the exchange of resistance genes between bacteria. Hence, decolonization or reduction of the gastrointestinal tract colonization of these multi-resistant bacteria needs to be urgently explored. Developing new non-antibiotic strategies to limit or eradicate multi-resistant bacteria carriage without globally disrupting the microbiota is considered a priority to fight against antibiotic resistance. Probiotics or Fecal Microbiota Transplantation are alternative strategies to antibiotics that have been considered to decolonize intestinal tract from MDR bacteria but there is currently no evidence demonstrating their efficacy. Lytic bacteriophages are viruses that kill bacteria and therefore could be considered as a promising strategy to combat antibiotic resistance. Successful decolonization by bacteriophages has already been observed clinically. Here, we discuss the current alternative strategies considered to decolonize the digestive tract of multidrug resistant bacteria, briefly describing probiotics and fecal microbiota transplantation approaches, and then detail the in vivo and in vitro studies using bacteriophages, while discussing their limits regarding the animal models used, the characteristics of phages used and their activity in regards of the gut anatomy.}, }
@article {pmid38075879, year = {2023}, author = {Zhang, RX and Xu, JT and Zhong, HJ and Cai, YL and Zhuang, YP and Xie, YT and He, XX}, title = {Gut microbiota from essential tremor patients aggravates tremors in mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1252795}, pmid = {38075879}, issn = {1664-302X}, abstract = {BACKGROUND AND OBJECTIVE: Essential tremor (ET) lacks effective treatments because its underlying mechanism is largely unknown, but may involve gut microbiota via the microbiome-gut-brain axis. We explored the effects of gut microbiota on ET in mice.<br><br>METHODS: Specific pathogen-free C57BL/6J mice were gavaged with stools from ET patients or matched healthy individuals. After 3&#x2009;weeks of gavaging, behavioral tests were performed on all mice. Next, each mouse was injected with harmaline to induce tremors. The tremor duration was recorded; the tremor score was estimated every 30&#x2009;min. Behavioral tests were repeated after modeling. Intestinal tissues and fecal samples of the mice were examined using histology and 16Sr DNA sequencing, respectively.<br><br>RESULTS: Compared with mice receiving microbiota from healthy controls, mice receiving fecal suspensions from ET patients showed worse performance in the pre-modeling behavioral tests. After modeling, ET-group mice showed significantly greater tremor scores, longer tremor duration, and worse motor performance. They also had significantly lower body weight and lower fecal pellet count. Pathological scoring revealed more severe intestinal lesions in ET-group mice. The 16S rDNA sequencing data revealed significant differences in microbiota indices, and a correlation between these indices and tremors in mice. Functional predictions indicated that the abundance of GABA-related enzymes was altered in ET-group mice.<br><br>CONCLUSION: Mice transplanted with gut microbiota from ET patients showed worse performance in behavioral tests. After modeling, ET-group mice presented longer tremor duration, higher tremor score, and worse motor performance. This study provides evidence for gut microbiota dysbiosis that may affect the pathogenesis of ET.}, }
@article {pmid38074650, year = {2023}, author = {Zhang, H and Xu, Z}, title = {Gut-lung axis: role of the gut microbiota in non-small cell lung cancer immunotherapy.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1257515}, pmid = {38074650}, issn = {2234-943X}, abstract = {Immunotherapy for non-small cell lung cancer (NSCLC) has advanced considerably over the past two decades. In particular, immune checkpoint inhibitors are widely used for treating NSCLC. However, the overall cure and survival rates of patients with NSCLC remain low. Therefore, continuous investigation into complementary treatments is necessary to expand the clinical advantages of immunotherapy to a larger cohort of patients with NSCLC. Recently, the distinctive role of the gut microbiota (GM) in the initiation, progression, and dissemination of cancer has attracted increasing attention. Emerging evidence indicates a close relationship between the gut and lungs, known as the gut-lung axis (GLA). In this review, we aim to provide a comprehensive summary of the current knowledge regarding the connection between the GM and the outcomes of immunotherapy in NSCLC, with particular focus on the recent understanding of GLA. Overall, promising GM-based therapeutic strategies have been observed to improve the effectiveness or reduce the toxicity of immunotherapy in patients with NSCLC, thus advancing the utilization of microbiota precision medicine.}, }
@article {pmid38073530, year = {2023}, author = {Taylor, VH and Kumar, V}, title = {Can we manage gut microbiome imbalances in patients with bipolar disorder with pharmacotherapy?.}, journal = {Expert opinion on pharmacotherapy}, volume = {24}, number = {18}, pages = {1957-1961}, doi = {10.1080/14656566.2023.2288287}, pmid = {38073530}, issn = {1744-7666}, mesh = {Humans ; *Bipolar Disorder/drug therapy ; *Gastrointestinal Microbiome ; *Microbiota ; Biomarkers ; }, abstract = {INTRODUCTION: A novel new area of exploration in the treatment of bipolar disorder is the gut brain axis. Studies have shown significant differences between the gut microbiome in those with bipolar disorder and those without the illness, as well as documented microbiome changes associated with the effects of bipolar pharmacotherapy and targeted microbial interventions. Although we have evidence suggesting the bi-directional relationship between the gut microbiome and psychiatric disorders, we are still unable to utilize this understanding clinically.<br><br>AREAS COVERED: We need to better understand the factors that impact the microbiome in this illness and vice versa.<br><br>EXPERT OPINION: Additionally, changes in gut microbiome in bipolar disorder might be used for biomarker identification with a potential to help in diagnosis and monitoring of the condition. It is an important area for further research and may provide improved therapeutic outcomes.}, }
@article {pmid38072872, year = {2024}, author = {Yao, S and Yagi, S and Sugimoto, T and Asahara, T and Uemoto, S and Hatano, E}, title = {Occult bacteremia in living donor liver transplantation: a prospective observational study of recipients and donors.}, journal = {Surgery today}, volume = {54}, number = {6}, pages = {596-605}, pmid = {38072872}, issn = {1436-2813}, support = {18K08567//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Liver Transplantation/adverse effects ; *Living Donors ; *Bacteremia/epidemiology/etiology/microbiology ; Prospective Studies ; Male ; Female ; Middle Aged ; Adult ; *Postoperative Complications/microbiology/epidemiology/etiology ; Incidence ; Gastrointestinal Microbiome ; Aged ; Feces/microbiology ; }, abstract = {PURPOSE: To investigate the incidence and clinical impact of occult bacteremia in liver transplantation (LT).<br><br>METHODS: This prospective observational study involved a fixed-point observation for up to 2&#xa0;weeks after living donor LT in 20 recipients, with 20 donors as comparison subjects. Bacteria in the blood samples were detected using the ribosomal RNA-targeted reverse-transcription quantitative polymerase chain reaction method. To identify the causality with the gut microbiota (GM), fecal samples were collected and analyzed simultaneously.<br><br>RESULTS: Occult bacteremia was identified in four recipients (20%) and three donors (15%) before the operation, and in seven recipients (35%) and five donors (25%) after the operation. Clostridium leptum subgroup, Prevotella, Colinesella, Enterobacteriaceae, and Streptococcus were the main pathogens responsible. Although it did not negatively affect the donor post-hepatectomy outcomes, the recipients with occult bacteremia had a higher rate of infectious complications post-LT. The GM analyses showed fewer post-LT predominant obligate anaerobes in both the recipients and donors with occult bacteremia.<br><br>CONCLUSIONS: Occult bacteremia is a common condition that occurs in both donors and recipients. While occult bacteremia generally remains subclinical in the healthy population, there is potential risk of the development of an apparent post-LT infection in recipients who are highly immunosuppressed.}, }
@article {pmid38072552, year = {2023}, author = {Li, T and Chen, H and Xu, B and Yu, M and Li, J and Shi, Y and Xia, S and Wu, S}, title = {Deciphering the interplay between LPS/TLR4 pathways, neurotransmitter, and deltamethrin-induced depressive-like behavior: Perspectives from the gut-brain axis.}, journal = {Pesticide biochemistry and physiology}, volume = {197}, number = {}, pages = {105697}, doi = {10.1016/j.pestbp.2023.105697}, pmid = {38072552}, issn = {1095-9939}, mesh = {Mice ; Humans ; Animals ; *Lipopolysaccharides/toxicity ; *Brain-Gut Axis ; Dysbiosis ; Toll-Like Receptor 4/metabolism ; Tight Junction Proteins ; }, abstract = {The improper use of deltamethrin (DM) can result in its accumulation in soil, water, food, and even the human body, which is associated with an elevated risk of neurotoxicity and behavioral abnormalities; however, the underlying mechanisms remain insufficiently investigated. Emerging evidence underscores the significance of the gut-brain axis in central nervous system (CNS) dysfunctions. Accordingly, this study investigates the role of the gut-brain axis in DM-induced behavioral anomalies in mice. The results showed that DM exposure induced depressive-like behavior, and the hippocampus, the region that is responsible for the modulation of emotional behavior, showed structural integrity disrupted (neuronal nuclear shrinkage and decreased tight junction protein expression). In addition, DM exposure led to compromised gut barrier integrity (disruptions on crypt surfaces and decreased tight junction protein expression), which might contribute to the gut bacterial-derived lipopolysaccharide (LPS) leakage into the bloodstream and reaching the brain, triggering LPS/toll-like receptor (TLR) 4 -mediated increases in brain pro-inflammatory cytokines. Subsequently, we observed a disturbance in neurotransmitter metabolic pathways following DM exposure, which inhibited the production of 5-hydroxytryptamine (5-HT). Additionally, DM exposure resulted in gut microbiota dysbiosis. Characteristic bacteria, such as Alistipes, Bifidobacterium, Gram-negative bacterium cTPY-13, and Odoribacter exhibited significant correlations with behavior, tight junction proteins, inflammatory response, and neurotransmitters. Further fecal microbiota transplantation (FMT) experiments suggested that DM-induced gut microbiota dysbiosis might contribute to depressive-like behavior. These results provide a new perspective on the toxicity mechanism of DM, indicating that its neurotoxicity may be partially regulated by the microbiota-gut-brain axis.}, }
@article {pmid38071977, year = {2024}, author = {Zhao, H and Li, W and Zhou, X and Pan, L and Feng, Y and Gao, P and Ji, J and Zhang, H and Zhao, K and Wang, C and Lu, Z}, title = {C-X-C Motif Chemokine Ligand 1 Promotes Colitis by Modulating the Gut Microbiota.}, journal = {Journal of innate immunity}, volume = {16}, number = {1}, pages = {33-44}, pmid = {38071977}, issn = {1662-8128}, mesh = {Animals ; Humans ; Mice ; *Colitis/chemically induced/metabolism ; Colon/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Ligands ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; }, abstract = {INTRODUCTION: C-X-C motif chemokine ligand 1 (CXCL1) is a potent neutrophil chemoattractant that plays a pivotal role in recruiting neutrophils during inflammatory conditions. This study explored the role of CXCL1 in modulating the gut microbiota, influencing neutrophil infiltration, and contributing to the development of colitis.<br><br>METHODS: We employed quantitative PCR to assess CXCL1 expression in colon samples. A mouse model of dextran sulfate sodium (DSS)-induced colitis was utilized to explore the progression of colitis in wild-type (WT) and CXCL1-deficient (CXCL1-/-) mice.<br><br>RESULTS: Colitis attenuation was evident in CXCL1-/- mice. Significant alterations were observed in the gut microbiome, as revealed by 16S rRNA gene sequencing. Furthermore, CXCL1-/- mice exhibited reduced gut permeability and diminished endotoxin levels in peripheral blood following DSS treatment compared to WT mice. In response to DSS treatment, WT mice showed a clear increase in neutrophil infiltration, while CXCL1-/- mice exhibited lower levels of infiltration. Fecal microbiota transplantation (FMT) using stools from CXCL1-/- mice alleviated DSS-induced colitis. Interestingly, FMT from patients with colitis increased CXCL1 and Ly6G expression in the colons of gut-sterilized mice. Clinical data analysis revealed elevated CXCL1 and CD15 expression in patients with colitis, with a positive correlation between the severity of colitis and the expression of CXCL1 and CD15.<br><br>CONCLUSION: These findings shed light on the pivotal role of CXCL1 in promoting colitis by modulating the gut microbiota.}, }
@article {pmid38071422, year = {2024}, author = {Sun, K and Fournier, M and Sundberg, AK and Song, IH}, title = {Maribavir: Mechanism of action, clinical, and translational science.}, journal = {Clinical and translational science}, volume = {17}, number = {1}, pages = {e13696}, pmid = {38071422}, issn = {1752-8062}, mesh = {Humans ; *Antiviral Agents ; Translational Science, Biomedical ; *Cytomegalovirus Infections/chemically induced/drug therapy ; Benzimidazoles ; Dichlororibofuranosylbenzimidazole/*analogs &amp; derivatives ; }, abstract = {Maribavir is an oral benzimidazole riboside for treatment of post-transplant cytomegalovirus (CMV) infection/disease that is refractory to prior antiviral treatment (with or without resistance). Through competitive inhibition of adenosine triphosphate, maribavir prevents the phosphorylation actions of UL97 to inhibit CMV DNA replication, encapsidation, and nuclear egress. Maribavir is active against CMV strains with viral DNA polymerase mutations that confer resistance to other CMV antivirals. After oral administration, maribavir is rapidly and highly absorbed (fraction absorbed >90%). The approved dose of 400 mg twice daily (b.i.d.) achieves a steady-state area under the curve per dosing interval of 128 h*μg/mL and trough concentration of 4.90 μg/mL (13.0 μM). Maribavir is highly bound to human plasma proteins (98%) with a small apparent volume of distribution of 27.3 L. Maribavir is primarily cleared by hepatic CYP3A4 metabolism; its major metabolite, VP44669 (pharmacologically inactive), is excreted in the urine and feces. There is no clinically relevant impact on maribavir pharmacokinetics by age, sex, race/ethnicity, body weight, transplant type, or hepatic/renal impairment status. In phase II dose-ranging studies, maribavir showed similar rates of CMV viral clearance across 400, 800, or 1200 mg b.i.d. groups, ranging from 62.5-70% in study 202 (NCT01611974) and 74-83% in study 203 (EudraCT 2010-024247-32). In the phase III SOLSTICE trial (NCT02931539), maribavir 400 mg b.i.d. demonstrated superior CMV viremia clearance at week 8 versus investigator-assigned treatments, with lower treatment discontinuation rates. Dysgeusia, nausea, vomiting, and diarrhea were commonly experienced adverse events among patients treated with maribavir in clinical trials.}, }
@article {pmid38068763, year = {2023}, author = {Komorniak, N and Kaczmarczyk, M and Łoniewski, I and Martynova-Van Kley, A and Nalian, A and Wroński, M and Kaseja, K and Kowalewski, B and Folwarski, M and Stachowska, E}, title = {Analysis of the Efficacy of Diet and Short-Term Probiotic Intervention on Depressive Symptoms in Patients after Bariatric Surgery: A Randomized Double-Blind Placebo Controlled Pilot Study.}, journal = {Nutrients}, volume = {15}, number = {23}, pages = {}, pmid = {38068763}, issn = {2072-6643}, mesh = {Humans ; *Gastric Bypass ; Depression/prevention &amp; control ; Pilot Projects ; *Bariatric Surgery/adverse effects ; Diet ; *Probiotics ; *Obesity, Morbid/surgery ; }, abstract = {(1) Background: studies have shown that some patients experience mental deterioration after bariatric surgery. (2) Methods: We examined whether the use of probiotics and improved eating habits can improve the mental health of people who suffered from mood disorders after bariatric surgery. We also analyzed patients' mental states, eating habits and microbiota. (3) Results: Depressive symptoms were observed in 45% of 200 bariatric patients. After 5 weeks, we noted an improvement in patients' mental functioning (reduction in BDI and HRSD), but it was not related to the probiotic used. The consumption of vegetables and whole grain cereals increased (DQI-I adequacy), the consumption of simple sugars and SFA decreased (moderation DQI-I), and the consumption of monounsaturated fatty acids increased it. In the feces of patients after RYGB, there was a significantly higher abundance of two members of the Muribaculaceae family, namely Veillonella and Roseburia, while those after SG had more Christensenellaceae R-7 group, Subdoligranulum, Oscillibacter, and UCG-005. (4) Conclusions: the noted differences in the composition of the gut microbiota (RYGB vs. SG) may be one of the determinants of the proper functioning of the gut-brain microbiota axis, although there is currently a need for further research into this topic using a larger group of patients and different probiotic doses.}, }
@article {pmid38065352, year = {2024}, author = {Jingyi, L and Lin, W and Yuan, C and Lingling, Z and Qianqian, J and Anlong, X and Yansong, G}, title = {Intravenous transplantation of bone marrow-derived mesenchymal stem cells improved behavioral deficits and altered fecal microbiota composition of BTBR mice.}, journal = {Life sciences}, volume = {336}, number = {}, pages = {122330}, doi = {10.1016/j.lfs.2023.122330}, pmid = {38065352}, issn = {1879-0631}, mesh = {Mice ; Animals ; Humans ; *Autism Spectrum Disorder/therapy ; Mice, Inbred C57BL ; Bone Marrow ; Mice, Inbred Strains ; *Gastrointestinal Microbiome ; *Mesenchymal Stem Cells ; }, abstract = {AIMS: It is recognized that autism spectrum disorder (ASD) is a highly complex neurodevelopmental disorder with communication deficits as well as multiple social barriers. The core symptoms of ASD are not treatable with current therapeutics. Therefore, finding new treatment strategies for ASD is urgently needed. Mesenchymal stem cells (MSC) have been shown to be a promising therapeutic approach in previous studies. However, the underlying mechanisms of MSC treatment for ASD through gut microbiota remain unclear and require further investigation.<br><br>MAIN METHODS: BTBR mice were used as ASD model and then randomly assigned to the human bone marrow-derived mesenchymal stem cell (hBMMSC) intravenous treatment group or vehicle treatment group. C57BL/6J (C57) mice served as control. Multiple social behavioral tests were performed during the 6-week period and fecal samples were collected at different time points for 16&#xa0;s rRNA sequencing analysis.<br><br>KEY FINDINGS: The administration of hBMMSC improved social deficits of BTBR mice in the open field test (OFT), light-dark box test (LBT), novel object recognition (NOR), and free social test (FST), while also significantly reducing stereotypic behaviors. Additionally, hBMMSC administration notably reversed the alterations of microbiota abundance in BTBR mice, particularly the Firmicutes/Bacteroidetes ratio. Several specific differential taxa were further selected and showed a correlation with the prognosis and behavioral scores of ASD.<br><br>SIGNIFICANCE: Overall, intravenous treatment with hBMMSC had a beneficial impact on ASD by ameliorating social deficits and modifying microbiota compositions. This outcome indicates that hBMMSC intravenous transplantation could be a promising therapeutic strategy for enhancing ASD symptoms improvements.}, }
@article {pmid38065343, year = {2024}, author = {D'arienzo, PD and Pinato, DJ}, title = {Fecal Microbiota Transplantation to Reverse Host-Related Determinants of Resistance to Anticancer Immunotherapy.}, journal = {Gastroenterology}, volume = {166}, number = {3}, pages = {535}, doi = {10.1053/j.gastro.2023.12.001}, pmid = {38065343}, issn = {1528-0012}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Immunotherapy ; }, }
@article {pmid38064388, year = {2023}, author = {Khurram, S and Asad, A and Fatima, SZ}, title = {Fecal microbiota transplantation: the need for effective treatment of Clostridioides difficile infection in Pakistan.}, journal = {Journal of infection in developing countries}, volume = {17}, number = {11}, pages = {1626-1627}, doi = {10.3855/jidc.17498}, pmid = {38064388}, issn = {1972-2680}, }
@article {pmid38062990, year = {2024}, author = {Dunbar, A and Drigo, B and Djordjevic, SP and Donner, E and Hoye, BJ}, title = {Impacts of coprophagic foraging behaviour on the avian gut microbiome.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {99}, number = {2}, pages = {582-597}, doi = {10.1111/brv.13036}, pmid = {38062990}, issn = {1469-185X}, support = {//University of South Australia's Science, Technology, Engineering, and Mathematics/ ; DE200100884//Australian Research Council/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Coprophagia ; Birds ; Diet/veterinary ; Feces ; }, abstract = {Avian gut microbial communities are complex and play a fundamental role in regulating biological functions within an individual. Although it is well established that diet can influence the structure and composition of the gut microbiota, foraging behaviour may also play a critical, yet unexplored role in shaping the composition, dynamics, and adaptive potential of avian gut microbiota. In this review, we examine the potential influence of coprophagic foraging behaviour on the establishment and adaptability of wild avian gut microbiomes. Coprophagy involves the ingestion of faeces, sourced from either self (autocoprophagy), conspecific animals (allocoprophagy), or heterospecific animals. Much like faecal transplant therapy, coprophagy may (i) support the establishment of the gut microbiota of young precocial species, (ii) directly and indirectly provide nutritional and energetic requirements, and (iii) represent a mechanism by which birds can rapidly adapt the microbiota to changing environments and diets. However, in certain contexts, coprophagy may also pose risks to wild birds, and their microbiomes, through increased exposure to chemical pollutants, pathogenic microbes, and antibiotic-resistant microbes, with deleterious effects on host health and performance. Given the potentially far-reaching consequences of coprophagy for avian microbiomes, and the dearth of literature directly investigating these links, we have developed a predictive framework for directing future research to understand better when and why wild birds engage in distinct types of coprophagy, and the consequences of this foraging behaviour. There is a need for comprehensive investigation into the influence of coprophagy on avian gut microbiotas and its effects on host health and performance throughout ontogeny and across a range of environmental perturbations. Future behavioural studies combined with metagenomic approaches are needed to provide insights into the function of this poorly understood behaviour.}, }
@article {pmid38062089, year = {2023}, author = {Qian, J and Lu, J and Cheng, S and Zou, X and Tao, Q and Wang, M and Wang, N and Zheng, L and Liao, W and Li, Y and Yan, F}, title = {Periodontitis salivary microbiota exacerbates colitis-induced anxiety-like behavior via gut microbiota.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {93}, pmid = {38062089}, issn = {2055-5008}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Histidine/adverse effects ; *Colitis/chemically induced/microbiology ; *Microbiota ; Anxiety/microbiology ; *Periodontitis ; }, abstract = {The gut-brain axis is a bidirectional communication system between the gut and central nervous system. Many host-related factors can affect gut microbiota, including oral bacteria, making the brain a vulnerable target via the gut-brain axis. Saliva contains a large number of oral bacteria, and periodontitis, a common oral disease, can change the composition of salivary microbiota. However, the role and mechanism of periodontitis salivary microbiota (PSM) on the gut-brain axis remain unclear. Herein, we investigated the nature and mechanisms of this relationship using the mice with dextran sulfate sodium salt (DSS)-induced anxiety-like behavior. Compared with healthy salivary microbiota, PSM worsened anxiety-like behavior; it significantly reduced the number of normal neurons and activated microglia in DSS mice. Antibiotic treatment eliminated the effect of PSM on anxiety-like behavior, and transplantation of fecal microbiota from PSM-gavaged mice exacerbated anxiety-like behavior. These observations indicated that the anxiety-exacerbating effect of PSM was dependent on the gut microbiota. Moreover, the PSM effect on anxiety-like behavior was not present in non-DSS mice, indicating that DSS treatment was a prerequisite for PSM to exacerbate anxiety. Mechanistically, PSM altered the histidine metabolism in both gut and brain metabolomics. Supplementation of histidine-related metabolites had a similar anxiety-exacerbating effect as that of PSM, suggesting that histidine metabolism may be a critical pathway in this process. Our results demonstrate that PSM can exacerbate colitis-induced anxiety-like behavior by directly affecting the host gut microbiota, emphasizing the importance of oral diseases in the gut-brain axis.}, }
@article {pmid38061593, year = {2024}, author = {Yu, Z and Xiaojia, L and Wei, Z and Jian, Z and Aiting, W and Jing, W and Lin, Y and Bangwei, C and Dan, Y}, title = {Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids.}, journal = {Pharmacological research}, volume = {199}, number = {}, pages = {107033}, doi = {10.1016/j.phrs.2023.107033}, pmid = {38061593}, issn = {1096-1186}, mesh = {Humans ; Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; CD8-Positive T-Lymphocytes/metabolism ; Programmed Cell Death 1 Receptor ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; *Flavonoids ; }, abstract = {Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally to mice following fecal microbiota transplantation from patients resistant to ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are presently unknown. In this present study, ATB-treated C57BL/6 J mice received FMT from patients with advanced NSCLC amenable to αPD-1. Additionally, subcutaneous LLC cells were injected into the mice. Baicalin oral gavage and αPD-1 injection were administered to the mice on days 3 and 9 after tumour inoculation. 16 S rRNA, metabolomics, and flow cytometry were utilized to clarify the mechanisms of baicalin's relief of immunosuppression. The results indicated that oral administration of baicalin enriched bacteria such as Akkermansia and Clostridia_UCG-014, resulted in an increase in SCFAs, which improved the ratio of PD-1[+] (CD8[+] T cell/Treg) and promoted the levels of IFN-γ[+] CD8[+] T cells and TNF-α[+] CD8[+] T cells within the tumour microenvironment. In conclusion, baicalin regulates the metabolites of the gut microbiota to improve the PD-1[+] (CD8[+] T cell/Treg) balance and circumvent anti-PD-1 resistance. This is achieved through the regulation of short-chain fatty acids.}, }
@article {pmid38057970, year = {2023}, author = {Cheng, Y and Tan, G and Zhu, Q and Wang, C and Ruan, G and Ying, S and Qie, J and Hu, X and Xiao, Z and Xu, F and Chen, L and Chen, M and Pei, Y and Zhang, H and Tian, Y and Chen, D and Liu, X and Huang, H and Wei, Y}, title = {Efficacy of fecal microbiota transplantation in patients with Parkinson's disease: clinical trial results from a randomized, placebo-controlled design.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2284247}, pmid = {38057970}, issn = {1949-0984}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Parkinson Disease/therapy ; *Gastrointestinal Microbiome ; Dysbiosis/therapy/etiology ; China ; Treatment Outcome ; Feces ; }, abstract = {The occurrence and development of Parkinson's disease (PD) have been demonstrated to be related to gut dysbiosis, however, the impact of fecal microbiota transplantation (FMT) on microbiota engraftment in PD patients is uncertain. We performed a randomized, placebo-controlled trial at the Department of Neurology, Army Medical University Southwest Hospital in China (ChiCTR1900021405) from February 2019 to December 2019. Fifty-six participants with mild to moderate PD (Hoehn-Yahr stage 1-3) were randomly assigned to the FMT and placebo group, 27 patients in the FMT group and 27 in the placebo group completed the whole trial. During the follow-up, no severe adverse effect was observed, and patients with FMT treatment showed significant improvement in PD-related autonomic symptoms compared with the placebo group at the end of this trial (MDS-UPDRS total score, group×time effect, B = -6.56 [-12.98, -0.13], P < 0.05). Additionally, FMT improved gastrointestinal disorders and a marked increase in the complexity of the microecological system in patients. This study demonstrated that FMT through oral administration is clinically feasible and has the potential to improve the effectiveness of current medications in the clinical symptoms of PD patients.}, }
@article {pmid38057705, year = {2023}, author = {Yang, C and Hu, T and Xue, X and Su, X and Zhang, X and Fan, Y and Shen, X and Dong, X}, title = {Multi-omics analysis of fecal microbiota transplantation's impact on functional constipation and comorbid depression and anxiety.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {389}, pmid = {38057705}, issn = {1471-2180}, support = {202102130501015//Key R&amp;D Program of Shanxi Province/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation ; Depression/therapy ; Multiomics ; Serotonin ; Constipation/therapy ; Feces/microbiology ; *Gastrointestinal Diseases ; Anxiety/therapy ; }, abstract = {BACKGROUND: Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted.<br><br>METHODS: We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients' fecal supernatants exposed to the QGP-1 cell model in vitro.<br><br>RESULTS: Our study demonstrated that patient's constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients' fecal supernatants increased 5-HT biosynthesis in QGP-1 cells.<br><br>CONCLUSION: FMT can relieve patients' constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms.}, }
@article {pmid38057297, year = {2023}, author = {Yan, M and Man, S and Sun, B and Ma, L and Guo, L and Huang, L and Gao, W}, title = {Gut liver brain axis in diseases: the implications for therapeutic interventions.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {443}, pmid = {38057297}, issn = {2059-3635}, support = {82074069//National Natural Science Foundation of China (National Science Foundation of China)/ ; 20YFZCSY00560//Natural Science Foundation of Tianjin Municipal Science and Technology Commission (Natural Science Foundation of Tianjin Municipal Science &amp; Technology Commission)/ ; }, mesh = {*Brain-Gut Axis ; Epigenesis, Genetic ; *Gastrointestinal Microbiome ; Liver/metabolism ; Brain ; }, abstract = {Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In the past few decades, breakthrough progress has been made in the gut liver brain axis, mainly through understanding its formation mechanism and increasing treatment strategies. In this review, we discuss various complex networks including barrier permeability, gut hormones, gut microbial metabolites, vagus nerve, neurotransmitters, immunity, brain toxic metabolites, β-amyloid (Aβ) metabolism, and epigenetic regulation in the gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet and nanotechnology application regulate the gut liver brain axis. Besides, some special treatments targeting gut-liver axis include farnesoid X receptor (FXR) agonists, takeda G protein-coupled receptor 5 (TGR5) agonists, glucagon-like peptide-1 (GLP-1) receptor antagonists and fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain axis embraces cognitive behavioral therapy (CBT), antidepressants and tryptophan metabolism-related therapies. Targeting liver-brain axis contains epigenetic regulation and Aβ metabolism-related therapies. In the future, a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.}, }
@article {pmid38057285, year = {2024}, author = {Wang, N and Gao, X and Huo, Y and Li, Y and Cheng, F and Zhang, Z}, title = {Lead exposure aggravates glucose metabolism disorders through gut microbiota dysbiosis and intestinal barrier damage in high-fat diet-fed mice.}, journal = {Journal of the science of food and agriculture}, volume = {104}, number = {5}, pages = {3057-3068}, doi = {10.1002/jsfa.13197}, pmid = {38057285}, issn = {1097-0010}, support = {//National Natural Scientific Funding of China/ ; //Postgraduate Research &amp; Practice Innovation Program of Jiangsu Province/ ; //Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, mesh = {Mice ; Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Lead/toxicity ; Dysbiosis/etiology/metabolism ; Mice, Inbred C57BL ; *Glucose Metabolism Disorders/etiology ; Fatty Acids, Volatile/metabolism ; Inflammation/etiology ; Glucose ; }, abstract = {BACKGROUND: Lead (Pb) is an ancient toxic metal and is still a major public health issue. Our previous study found that Pb exposure promotes metabolic disorders in obese mice, but the molecular mechanisms remain unclear. The present study explored the effects of Pb exposure on glucose homeostasis in mice fed a normal diet (ND) and high-fat diet (HFD) from the perspective of gut microbiota.<br><br>RESULTS: Pb exposure had little effect on glucose metabolism in ND mice, but exacerbated hyperglycemia and insulin resistance, and impaired glucose tolerance in HFD mice. Pb exposure impaired intestinal tight junctions and mucin expression in HFD mice, increasing intestinal permeability and inflammation. Moreover, Pb exposure altered the composition and structure of the gut microbiota and decreased short-chain fatty acids (SCFAs) levels in HFD mice. Correlation analysis revealed that the gut microbiota and SCFAs were significantly correlated with the gut barrier and glucose homeostasis. Furthermore, the fecal microbiota transplantation from Pb-exposed HFD mice resulted in glucose homeostasis imbalance, intestinal mucosal structural damage and inflammation in recipient mice. However, Pb did not exacerbate the metabolic toxicity in HFD mice under depleted gut microbiota.<br><br>CONCLUSION: The findings of the present study suggest that Pb induces impairment of glucose metabolism in HFD mice by perturbing the gut microbiota. Our study offers new perspectives on the mechanisms of metabolic toxicity of heavy metals and demonstrates that the gut microbiota may be a target of action for heavy metal exposure. &#xa9; 2023 Society of Chemical Industry.}, }
@article {pmid38056511, year = {2024}, author = {Sehgal, K and Yadav, D and Saha, S and Mara, K and Grover, M and Khanna, S}, title = {Sex-Discordant Fecal Microbiota Transplantation for Clostridioides difficile May Increase Risk of Postinfection Irritable Bowel Syndrome.}, journal = {Gastroenterology}, volume = {166}, number = {4}, pages = {704-706.e2}, doi = {10.1053/j.gastro.2023.11.295}, pmid = {38056511}, issn = {1528-0012}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Irritable Bowel Syndrome/diagnosis/therapy ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; *Gastrointestinal Microbiome ; Treatment Outcome ; Recurrence ; }, }
@article {pmid38056144, year = {2024}, author = {Liu, YF and Xie, WJ and Xi, P and Zhang, ZC and Chen, R and Fu, SQ and Lei, KY and Liu, J and Cheng, XF and Nie, YC and Yang, XR and Ma, M and Sun, T and Gong, BB}, title = {Astaxanthin alleviates chronic prostatitis/chronic pelvic pain syndrome by increasing colonization of Akkermansia muciniphila in the intestine.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {123}, number = {}, pages = {155249}, doi = {10.1016/j.phymed.2023.155249}, pmid = {38056144}, issn = {1618-095X}, mesh = {Humans ; Male ; Mice ; Animals ; *Prostatitis/drug therapy ; RNA, Ribosomal, 16S ; Inflammation/drug therapy ; Pelvic Pain/drug therapy/metabolism ; Intestines ; *Chronic Pain ; Akkermansia ; Xanthophylls ; }, abstract = {BACKGROUND: Astaxanthin (AST) is a natural compound with anti-inflammatory/immunomodulatory properties that has been found to have probiotic properties. However, the role and mechanism of AST in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still not fully understood.<br><br>PURPOSE: The aim of this study was to evaluate the effect of AST on CP/CPPS and elucidate the mediating role of the gut microbiota.<br><br>MATERIALS AND METHODS: An experimental autoimmune prostatitis (EAP) mouse model was utilized to test the potential role of AST on CP/CPPS. Antibiotic cocktail (ABX) treatment and fecal microbiota transplantation (FMT) were used to elucidate the gut microbiota-mediated effects on AST. In addition, 16S rRNA gene sequencing and qRT-PCR analyses were used to analyze changes in the gut microbiota of EAP mice and CP/CPPS patients. Finally, the mechanism by which AST exerts a protective effect on CP/CPPS was explored by untargeted metabolomics and gut barrier function assays.<br><br>RESULTS: Oral administration of AST reduced prostate inflammation scores, alleviated tactile sensitization of the pelvic region in EAP mice, reduced CD4+ T cell and CD68+ macrophage infiltration in the prostatic interstitium, and inhibited the up-regulation of systemic and localized pain/pro-inflammatory mediators in the prostate. After ABX, the protective effect of AST against CP/CPPS was attenuated, whereas colonization with fecal bacteria from AST-treated EAP mice alleviated CP/CPPS. 16S rRNA gene sequencing and qRT-PCR analyses showed that Akkermansia muciniphila in the feces of EAP mice and CP/CPPS patients showed a trend toward a decrease, which was associated with poor progression of CP/CPPS. In contrast, oral administration of AST increased the relative abundance of A. muciniphila, and oral supplementation with A. muciniphila also alleviated inflammation and pain in EAP mice. Finally, we demonstrated that both AST and A. muciniphila interventions increased serum levels of SCFAs acetate, up-regulated expression of colonic tight junction markers, and decreased serum lipopolysaccharide levels in EAP mice.<br><br>CONCLUSION: Our results showed that AST improved CP/CPPS by up-regulating A. muciniphila, which provides new potentially effective strategies and ideas for CP/CPPS management.}, }
@article {pmid38055355, year = {2023}, author = {He, K and Gao, Q and Su, J and Shang, H and Meng, X and Jiang, S and Liu, D and Huang, B}, title = {Gut Microbiome and Metabolomics Study of Selenium-Enriched Kiwifruit Regulating Hyperlipidemia in Mice Induced by a High-Fat Diet.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {50}, pages = {20386-20401}, doi = {10.1021/acs.jafc.3c00108}, pmid = {38055355}, issn = {1520-5118}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Diet, High-Fat/adverse effects ; *Hyperlipidemias/drug therapy/etiology ; *Selenium ; Mice, Inbred C57BL ; Metabolomics ; Lipid Metabolism ; Mammals ; }, abstract = {Our previous study showed that as a substitute for statins, selenium-enriched kiwifruit (Se-Kiwi) might reduce blood lipids and protect the liver in Kunming mice, but the underlying mechanism remains unclear. Metabolic regulation of mammalian intestinal microflora plays an important role in obesity and related diseases induced by a high-fat diet (HFD). Here, samples of serum, liver, colon, and fresh feces from the Se-Kiwi-treated hyperlipidemia C57BL/6J mouse model were collected. Based on metabolome (UHPLC-Q-TOF MS) and gut microbiome (16S rDNA) analyses as well as the integrative analysis of physiological and biochemical indices and pathological data of mice, we aimed to systematically illustrate the gut microbiome and metabolomics mechanism of Se-Kiwi in HFD-induced hyperlipidemic mice. As a result, Se-Kiwi can significantly increase the abundance of potentially beneficial gut bacteria such as Parabacteroides, Bacteroides, and Allobaculum in the colon and improve hyperlipidemia by regulating the digestion and absorption of vitamins, pyrimidine metabolism, purine metabolism, and other metabolic pathways, which have been confirmed by the following fecal microbiota transplantation experiment. This process was significantly regulated by the Ada, Gda, Pank1, Ppara, Pparg, and Cd36 genes. These findings may provide a theoretical basis for the research and development of selenium-enriched functional foods in the treatment of hyperlipidemia.}, }
@article {pmid38053512, year = {2023}, author = {Qi, L and Peng, J and Huang, X and Zhou, T and Tan, G and Li, F}, title = {Longitudinal dynamics of gut microbiota in the pathogenesis of acute graft-versus-host disease.}, journal = {Cancer medicine}, volume = {12}, number = {24}, pages = {21567-21578}, pmid = {38053512}, issn = {2045-7634}, support = {20212BCG74001//Science and Technology Innovation Base Construction Project of Jiangxi Province/ ; 20211ZDG02006//Science and Technology Innovation Base Construction Project of Jiangxi Province/ ; }, mesh = {Acinetobacter ; *Gastrointestinal Microbiome ; Transplantation, Homologous/adverse effects ; Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Tumor Necrosis Factor-alpha ; *Graft vs Host Disease/genetics ; Acute Disease ; }, abstract = {AIM: The gut microbiota has been reported to be associated with acute graft-versus-host disease (aGvHD) in hematopoietic stem cell transplantation (HSCT). Dynamic surveillance of the microbiota is required to understand the detailed pathogenesis involved in the process of aGvHD.<br><br>METHODS: Fecal samples were collected prospectively at four timepoints, including pre-HSCT (T1), graft infusion (T2), neutrophil engraftment (T3), and 30&#x2009;days after transplantation (T4). Fecal samples were profiled by 16S ribosomal RNA gene sequencing to assess the microbiota composition.<br><br>RESULTS: From the T1 to T4 timepoint, the diversity of the gut microbiota decreased, and the dominant species also changed, with a decrease in the obligate anaerobic bacteria and a shift toward a "pathogenic community". Compared with non-aGvHD patients, aGvHD patients had a lower abundance of Roseburia at T1 and a higher abundance of Acinetobacter johnsonii at T2. Furthermore, Acinetobacter johnsonii was negatively correlated with the secretion of IL-4 and TNF-&#x3b1;. At T3, Rothia mucilaginos was demonstrated to be linked with a decreased risk of aGvHD, which was accompanied by decreased secretion of IL-8. At T4, higher abundances of Lactobacillus paracasei and Acinetobacter johnsonii were identified to be related with aGvHD. Lactobacillus paracasei was associated with the downregulation of IL-10, and Acinetobacter johnsonii was associated with the downregulation of IL-2 and TNF-&#x3b1;.<br><br>CONCLUSIONS: Dynamic changes in gut microbiota composition and related cytokines were found to be related to aGvHD, including pathogenic or protective changes. These findings suggested that manipulation of gut microbiota at different timepoints might be a promising avenue for preventing or treating this common complication.}, }
@article {pmid38052405, year = {2024}, author = {Yu, Z and Han, J and Li, L and Zhang, Q and Chen, A and Chen, J and Wang, K and Jin, J and Li, H and Chen, G}, title = {Chronic triclosan exposure induce impaired glucose tolerance by altering the gut microbiota.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {183}, number = {}, pages = {114305}, doi = {10.1016/j.fct.2023.114305}, pmid = {38052405}, issn = {1873-6351}, mesh = {Humans ; Rats ; Animals ; *Glucose Intolerance/chemically induced ; *Triclosan/toxicity ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Glucose ; }, abstract = {Triclosan (TCS) is an antimicrobial compound incorporated into more than 2000 consumer products. This compound is frequently detected in the human body and causes ubiquitous contamination in the environment, thereby raising concerns about its impact on human health and environmental pollution. Here, we demonstrated that 20 weeks' exposure of TCS drove the development of glucose intolerance by inducing compositional and functional alterations in intestinal microbiota in rats. Fecal-transplantation experiments corroborated the involvement of gut microbiota in TCS-induced glucose-tolerance impairment. 16S rRNA gene-sequencing analysis of cecal contents showed that TCS disrupted the gut microbiota composition in rats and increased the ratio of Firmicutes to Bacteroidetes. Cecal metabolomic analyses detected that TCS altered host metabolic pathways that are linked to host glucose and amino acid metabolism, particularly branched-chain amino acid (BCAA) biosynthesis. BCAA measurement confirmed the increase in serum BCAAs in rats exposed to TCS. Western blot and immunostaining results further confirmed that elevated BCAAs stimulated mTOR, a nutrient-sensing complex, and following IRS-1 serine phosphorylation, resulted in insulin resistance and glucose intolerance. These results suggested that TCS may induce glucose metabolism imbalance by regulating BCAA concentration by remodeling the gut microbiota.}, }
@article {pmid38052208, year = {2023}, author = {Cerdó, T and Ruiz-Rodríguez, A and Acuña, I and Torres-Espínola, FJ and Menchén-Márquez, S and Gámiz, F and Gallo, M and Jehmlich, N and Haange, SB and von Bergen, M and Campoy, C and Suárez, A}, title = {Infant gut microbiota contributes to cognitive performance in mice.}, journal = {Cell host &amp; microbe}, volume = {31}, number = {12}, pages = {1974-1988.e4}, doi = {10.1016/j.chom.2023.11.004}, pmid = {38052208}, issn = {1934-6069}, mesh = {Humans ; Infant ; Animals ; Mice ; *Gastrointestinal Microbiome ; Histidine ; *Microbiota ; Feces/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {Gut microbiota has been linked to infant neurodevelopment. Here, an association between infant composite cognition and gut microbiota composition is established as soon as 6 months. Higher diversity and evenness characterize microbial communities of infants with composite cognition above (Inf-aboveCC) versus below (Inf-belowCC) median values. Metaproteomic and metabolomic analyses establish an association between microbial histidine ammonia lyase and infant histidine metabolome with cognition. Fecal transplantation from Inf-aboveCC versus Inf-belowCC donors into germ-free mice shows that memory, assessed by a novel object recognition test, is a transmissible trait. Furthermore, Inf-aboveCC mice are enriched in species belonging to Phocaeicola, as well as Bacteroides and Bifidobacterium, previously linked to cognition. Finally, Inf-aboveCC mice show lower fecal histidine and urocanate:histidine and urocanate:glutamate ratios in the perirhinal cortex compared to Inf-belowCC mice. Overall, these findings reveal a causative role of gut microbiota on infant cognition, pointing at the modulation of histidine metabolite levels as a potential underlying mechanism.}, }
@article {pmid38052097, year = {2024}, author = {Cooper, J and Markovinovic, A and Coward, S and Herauf, M and Shaheen, AA and Swain, M and Panaccione, R and Ma, C and Lu, C and Novak, K and Kroeker, KI and Ng, SC and Kaplan, GG}, title = {Incidence and Prevalence of Primary Sclerosing Cholangitis: A Meta-analysis of Population-based Studies.}, journal = {Inflammatory bowel diseases}, volume = {30}, number = {11}, pages = {2019-2026}, pmid = {38052097}, issn = {1536-4844}, support = {PJT-162393//CIHR/Canada ; G-2106-04697//Leona M. and Harry B. Helmsley Charitable Trust/ ; //Study of Inflammatory Bowel Disease/ ; PJT-162393//CIHR/Canada ; }, mesh = {Humans ; *Cholangitis, Sclerosing/epidemiology ; Incidence ; Prevalence ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis is a chronic liver disease associated with significant morbidity, mortality, and healthcare utilization. We conducted a systematic review and meta-analysis of population-based studies of the incidence and prevalence of primary sclerosing cholangitis.<br><br>METHODS: Medline and Embase were systematically searched to identify population-based studies of a defined geographic area and reported the incidence or prevalence of primary sclerosing cholangitis in the general population. Meta-analyses, using random-effects, were performed to calculate overall and country-specific incidence (per 100 000 persons/year) and prevalence rates (per 100 000 persons) with 95% confidence intervals.<br><br>RESULTS: The 14 studies on incidence and the 12 for prevalence originated from North America, Asia, Europe, and Oceania. Incidence and prevalence rates of primary sclerosing cholangitis were 0.87 (95% confidence interval, 0.59-1.29) and 13.53 (95% confidence interval, 10.20-17.94) per 100 000 persons, respectively.<br><br>CONCLUSIONS: Both the prevalence and incidence of primary sclerosing cholangitis is low in the general population. Future studies on the incidence and prevalence of primary sclerosing cholangitis in the general population should be directed at Asia, Africa, and Latin America to allow for a more robust assessment of the global epidemiology of primary sclerosing cholangitis.}, }
@article {pmid38051967, year = {2023}, author = {Kelly, CR and Allegretti, JR}, title = {Review Article: Gastroenterology and Clostridium difficile Infection: Past, Present, and Future.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {Suppl 6}, pages = {S463-S470}, doi = {10.1093/cid/ciad644}, pmid = {38051967}, issn = {1537-6591}, mesh = {Humans ; Feces ; *Gastroenterology ; *Clostridioides difficile ; Gastrointestinal Tract ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Recurrence ; Treatment Outcome ; }, abstract = {Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists. The emergence of standardized, approved live biotherapeutic products for treatment of recurrent CDI is an inflection point in our management of this difficult clinical problem, and real-world performance of these therapies will inform optimal treatment algorithms.}, }
@article {pmid38051964, year = {2023}, author = {Lavoie, T and Appaneal, HJ and LaPlante, KL}, title = {Advancements in Novel Live Biotherapeutic Products for Clostridioides difficile Infection Prevention.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {Suppl 6}, pages = {S447-S454}, doi = {10.1093/cid/ciad639}, pmid = {38051964}, issn = {1537-6591}, support = {//Seres and Ferring/ ; }, mesh = {Humans ; Dysbiosis/therapy ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; *Clostridium Infections/prevention &amp; control/drug therapy ; Feces/microbiology ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {The profound impact of the human microbiome on health and disease has captivated the interest of clinical and scientific communities. The human body hosts a vast array of microorganisms collectively forming the human microbiome, which significantly influences various physiological processes and profoundly shapes overall well-being. Notably, the gut stands out as an exceptional reservoir, harboring the most significant concentration of microorganisms, akin to an organ in itself. The gut microbiome's composition and function are influenced by genetics, environment, age, underlying conditions, and antibiotic usage, leading to dysbiosis and pathogenesis, such as Clostridioides difficile infection (CDI). Conventional CDI treatment, involving antibiotics like oral vancomycin and fidaxomicin, fails to address dysbiosis and may further disrupt gut microbial communities. Consequently, emerging therapeutic strategies are focused on targeting dysbiosis and restoring gut microbiota to advance CDI therapeutics. Fecal microbiota transplantation (FMT) has demonstrated remarkable efficacy in treating recurrent CDI by transferring processed stool from a healthy donor to a recipient, restoring gut dysbiosis and enhancing bacterial diversity. Moreover, 2 newer Food and Drug Administration (FDA)-approved live biotherapeutic products (LBP), namely, Fecal Microbiota Live-JSLM and Fecal Microbiota Spores Live-BRPK, have shown promise in preventing CDI recurrence. This review explores the role of the gut microbiota in preventing and treating CDI, with an emphasis on gut-based interventions like FMT and fecal microbiota-based products that hold potential for gut restoration and prevention of CDI recurrence. Understanding the microbiome's impact on CDI prevention and treatment offers valuable insights for advancing future CDI therapeutics.}, }
@article {pmid38051896, year = {2024}, author = {Huang, Q and Wei, M and Feng, X and Luo, Y and Liu, Y and Xia, J}, title = {Hemorrhagic transformation in patients with large-artery atherosclerotic stroke is associated with the gut microbiota and lipopolysaccharide.}, journal = {Neural regeneration research}, volume = {19}, number = {7}, pages = {1532-1540}, pmid = {38051896}, issn = {1673-5374}, abstract = {Hemorrhagic transformation is a major complication of large-artery atherosclerotic stroke (a major ischemic stroke subtype) that worsens outcomes and increases mortality. Disruption of the gut microbiota is an important feature of stroke, and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation pathogenesis. We aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in large-artery atherosclerotic stroke. An observational retrospective study was conducted. From May 2020 to September 2021, blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy, as well as 16 healthy controls. Patients with stroke who developed hemorrhagic transformation (n = 15) were compared to those who did not develop hemorrhagic transformation (n = 17) and with healthy controls. The gut microbiota was assessed through 16S ribosomal ribonucleic acid sequencing. We also examined key components of the lipopolysaccharide pathway: lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14. We observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transformation group compared with the healthy controls. The patients with ischemic stroke who developed hemorrhagic transformation exhibited altered gut microbiota composition, in particular an increase in the relative abundance and diversity of members belonging to the Enterobacteriaceae family. Plasma lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transformation group. lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14 concentrations were associated with increased abundance of Enterobacteriaceae. Next, the role of the gut microbiota in hemorrhagic transformation was evaluated using an experimental stroke rat model. In this model, transplantation of the gut microbiota from hemorrhagic transformation rats into the recipient rats triggered higher plasma levels of lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14. Taken together, our findings demonstrate a noticeable change in the gut microbiota and lipopolysaccharide-related inflammatory response in stroke patients with hemorrhagic transformation. This suggests that maintaining a balanced gut microbiota may be an important factor in preventing hemorrhagic transformation after stroke.}, }
@article {pmid38047407, year = {2024}, author = {Liu, X and Li, J and Shi, M and Fu, J and Wang, Y and Kang, W and Liu, J and Zhu, F and Huang, K and Chen, X and Liu, Y}, title = {Melatonin improves cholestatic liver disease via the gut-liver axis.}, journal = {Journal of pineal research}, volume = {76}, number = {1}, pages = {e12929}, doi = {10.1111/jpi.12929}, pmid = {38047407}, issn = {1600-079X}, support = {32102741//National Natural Science Foundation of China/ ; BK20210399//Natural Science Foundation of Jiangsu Province/ ; }, mesh = {Mice ; Animals ; *Melatonin/pharmacology/metabolism ; Liver/metabolism ; *Cholestasis/drug therapy/metabolism/pathology ; *Liver Diseases/metabolism/pathology ; Bile Acids and Salts/metabolism/pharmacology ; Mice, Knockout ; Liver Cirrhosis/chemically induced/drug therapy/metabolism ; Mice, Inbred C57BL ; }, abstract = {Cholestatic liver disease is characterized by disturbances in the intestinal microbiota and excessive accumulation of toxic bile acids (BA) in the liver. Melatonin (MT) can improve liver diseases. However, the underlying mechanism remains unclear. This study aimed to explore the mechanism of MT on hepatic BA synthesis, liver injury, and fibrosis in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed and Mdr2[-/-] mice. MT significantly improved hepatic injury and fibrosis with a significant decrease in hepatic BA accumulation in DDC-fed and Mdr2[-/-] mice. MT reprogramed gut microbiota and augmented fecal bile salt hydrolase activity, which was related to increasing intestinal BA deconjugation and fecal BA excretion in both DDC-fed and Mdr2[-/-] mice. MT significantly activated the intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF-15) axis and subsequently inhibited hepatic BA synthesis in DDC-fed and Mdr2[-/-] mice. MT failed to improve DDC-induced liver fibrosis and BA synthesis in antibiotic-treated mice. Furthermore, MT provided protection against DDC-induced liver injury and fibrosis in fecal microbiota transplantation mice. MT did not decrease liver injury and fibrosis in DDC-fed intestinal epithelial cell-specific FXR knockout mice, suggesting that the intestinal FXR mediated the anti-fibrosis effect of MT. In conclusion, MT ameliorates cholestatic liver diseases by remodeling gut microbiota and activating intestinal FXR/FGF-15 axis-mediated inhibition of hepatic BA synthesis and promotion of BA excretion in mice.}, }
@article {pmid38047235, year = {2023}, author = {Fremin, BJ and Bhatt, AS and Kyrpides, NC}, title = {Identification of over ten thousand candidate structured RNAs in viruses and phages.}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {5630-5639}, pmid = {38047235}, issn = {2001-0370}, support = {R01 AI148623/AI/NIAID NIH HHS/United States ; }, abstract = {Structured RNAs play crucial roles in viruses, exerting influence over both viral and host gene expression. However, the extensive diversity of structured RNAs and their ability to act in cis or trans positions pose challenges for predicting and assigning their functions. While comparative genomics approaches have successfully predicted candidate structured RNAs in microbes on a large scale, similar efforts for viruses have been lacking. In this study, we screened over 5 million DNA and RNA viral sequences, resulting in the prediction of 10,006 novel candidate structured RNAs. These predictions are widely distributed across taxonomy and ecosystem. We found transcriptional evidence for 206 of these candidate structured RNAs in the human fecal microbiome. These candidate RNAs exhibited evidence of nucleotide covariation, indicative of selective pressure maintaining the predicted secondary structures. Our analysis revealed a diverse repertoire of candidate structured RNAs, encompassing a substantial number of putative tRNAs or tRNA-like structures, Rho-independent transcription terminators, and potentially cis-regulatory structures consistently positioned upstream of genes. In summary, our findings shed light on the extensive diversity of structured RNAs in viruses, offering a valuable resource for further investigations into their functional roles and implications in viral gene expression and pave the way for a deeper understanding of the intricate interplay between viruses and their hosts at the molecular level.}, }
@article {pmid38046820, year = {2023}, author = {Roggiani, S and Mengoli, M and Conti, G and Fabbrini, M and Brigidi, P and Barone, M and D'Amico, F and Turroni, S}, title = {Gut microbiota resilience and recovery after anticancer chemotherapy.}, journal = {Microbiome research reports}, volume = {2}, number = {3}, pages = {16}, pmid = {38046820}, issn = {2771-5965}, abstract = {Although research on the role of the gut microbiota (GM) in human health has sharply increased in recent years, what a "healthy" gut microbiota is and how it responds to major stressors is still difficult to establish. In particular, anticancer chemotherapy is known to have a drastic impact on the microbiota structure, potentially hampering its recovery with serious long-term consequences for patients' health. However, the distinguishing features of gut microbiota recovery and non-recovery processes are not yet known. In this narrative review, we first investigated how gut microbiota layouts are affected by anticancer chemotherapy and identified potential gut microbial recovery signatures. Then, we discussed microbiome-based intervention strategies aimed at promoting resilience, i.e., the rapid and complete recovery of a healthy gut microbial network associated with a better prognosis after such high-impact pharmacological treatments.}, }
@article {pmid38045814, year = {2023}, author = {Gómez-Gallego, C and El-Nezami, H}, title = {Editorial: Novel developments for promoting health through microbiota modulation.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1331665}, pmid = {38045814}, issn = {2296-861X}, }
@article {pmid38045612, year = {2023}, author = {Brüssow, H}, title = {The human microbiome project at ten years - some critical comments and reflections on "our third genome", the human virome.}, journal = {Microbiome research reports}, volume = {2}, number = {1}, pages = {7}, pmid = {38045612}, issn = {2771-5965}, abstract = {The Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable exception of fecal microbiota transplantation in Clostridioides difficile infection, practical application of microbiome intervention has only achieved modest clinical effects. It is argued here that we need criteria for the link between microbiome and disease modelled on the links between pathogens and infectious disease in Koch's postulates. The most important question is whether the microbiome change is a cause of the given disease or a consequence of a pathology leading to disease where the microbiome change is only a parallel event without a causal connection to the disease - in philosophical parlance, an epiphenomenon. Also discussed here is whether human virome research is a necessary complement to the microbiome project with a high potential for practical applications.}, }
@article {pmid38045189, year = {2023}, author = {Chen, JH and Zhao, CL and Li, YS and Yang, YB and Luo, JG and Zhang, C and Wang, L}, title = {Moutai Distiller's grains Polyphenol extracts and rutin alleviate DSS-induced colitis in mice: Modulation of gut microbiota and intestinal barrier function （R2）.}, journal = {Heliyon}, volume = {9}, number = {11}, pages = {e22186}, pmid = {38045189}, issn = {2405-8440}, abstract = {Distiller's grains, byproducts of the brewing process, represent a valuable resource for extracting natural phenolic compounds due to their significant global production. This study presents the first evidence of the protective effects of Moutai distiller's grain polyphenol extract (MDGP) on dextran sulfate sodium (DSS)-induced colitis in mice. These protective effects manifest predominantly through the amelioration of general colitis indices and histopathological improvements. Utilizing liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), the main components of MDGP were identified as rutin, quercetin, naringenin, and dihydroquercetin. Moreover, a novel mechanism was elucidated by which rutin, the primary active component of MDGP, alleviates DSS-induced colitis. Assessment of intestinal barrier function, microbial sequencing, fecal transplantation, and antibiotic depletion experiments revealed that rutin suppresses the abundance of pathogenic bacteria (Helicobacter, Klebsiella, and Veillonella) while promoting the proliferation of beneficial bacteria (Ruminococcus_torques_group, Lachnoclostridium, and norank_f__Muribaculaceae). This modulation culminates in elevated butyric acid concentrations within short-chain fatty acids (SCFAs), amplified integrity of tight (ZO-1, occludin) and adherent (E-cadherin, β-catenin) junctional complexes, fortified intestinal barrier function, and diminished intestinal inflammation.This investigation accentuates the innovative therapeutic potential of MDGP and its main active component, rutin, in assuaging DSS-induced intestinal inflammation and fortifying the intestinal barrier through a mechanism predominantly mediated by the intestinal microbiota. Such insights potentially elevate the prominence of distiller's grains in the realm of functional food development.}, }
@article {pmid38044504, year = {2023}, author = {Meade, S and Liu Chen Kiow, J and Massaro, C and Kaur, G and Squirell, E and Bressler, B and Lunken, G}, title = {Gut microbiome-associated predictors as biomarkers of response to advanced therapies in inflammatory bowel disease: a systematic review.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2287073}, pmid = {38044504}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/microbiology ; Feces/microbiology ; Fecal Microbiota Transplantation ; Biomarkers/analysis ; }, abstract = {Loss of response to therapy in inflammatory bowel disease (IBD) has led to a surge in research focusing on precision medicine. Three systematic reviews have been published investigating the associations between gut microbiota and disease activity or IBD therapy. We performed a systematic review to investigate the microbiome predictors of response to advanced therapy in IBD. Unlike previous studies, our review focused on predictors of response to therapy; so the included studies assessed microbiome predictors before the proposed time of response or remission. We also provide an update of the available data on mycobiomes and viromes. We highlight key themes in the literature that may serve as future biomarkers of treatment response: the abundance of fecal SCFA-producing bacteria and opportunistic bacteria, metabolic pathways related to butyrate synthesis, and non-butyrate metabolomic predictors, including bile acids (BAs), amino acids, and lipids, as well as mycobiome predictors of response.}, }
@article {pmid38042820, year = {2023}, author = {Swarte, JC and Knobbe, TJ and Björk, JR and Gacesa, R and Nieuwenhuis, LM and Zhang, S and Vila, AV and Kremer, D and Douwes, RM and Post, A and Quint, EE and Pol, RA and Jansen, BH and ,  and de Borst, MH and de Meijer, VE and Blokzijl, H and Berger, SP and Festen, EAM and Zhernakova, A and Fu, J and Harmsen, HJM and Bakker, SJL and Weersma, RK}, title = {Health-related quality of life is linked to the gut microbiome in kidney transplant recipients.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {7968}, pmid = {38042820}, issn = {2041-1723}, mesh = {Humans ; Quality of Life ; *Gastrointestinal Microbiome/genetics ; *Kidney Transplantation/adverse effects ; Feces/microbiology ; Dysbiosis/microbiology ; }, abstract = {Kidney transplant recipients (KTR) have impaired health-related quality of life (HRQoL) and suffer from intestinal dysbiosis. Increasing evidence shows that gut health and HRQoL are tightly related in the general population. Here, we investigate the association between the gut microbiome and HRQoL in KTR, using metagenomic sequencing data from fecal samples collected from 507 KTR. Multiple bacterial species are associated with lower HRQoL, many of which have previously been associated with adverse health conditions. Gut microbiome distance to the general population is highest among KTR with an impaired physical HRQoL (R = -0.20, P = 2.3 × 10[-65]) and mental HRQoL (R = -0.14, P = 1.3 × 10[-3]). Physical and mental HRQoL explain a significant part of variance in the gut microbiome (R[2] = 0.58%, FDR = 5.43 × 10[-4] and R[2] = 0.37%, FDR = 1.38 × 10[-3], respectively). Additionally, multiple metabolic and neuroactive pathways (gut brain modules) are associated with lower HRQoL. While the observational design of our study does not allow us to analyze causality, we provide a comprehensive overview of the associations between the gut microbiome and HRQoL while controlling for confounders.}, }
@article {pmid38037086, year = {2023}, author = {Deng, ZL and Pieper, DH and Stallmach, A and Steube, A and Vital, M and Reck, M and Wagner-Döbler, I}, title = {Engraftment of essential functions through multiple fecal microbiota transplants in chronic antibiotic-resistant pouchitis-a case study using metatranscriptomics.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {269}, pmid = {38037086}, issn = {2049-2618}, support = {FP7/2007-2013//Innovative Medicines Initiative Joint Undertaking/ ; FP7/2007-2013//Innovative Medicines Initiative Joint Undertaking/ ; FP7/2007-2013//Innovative Medicines Initiative Joint Undertaking/ ; TRR 51//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Pouchitis/therapy/diagnosis/microbiology ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; Feces/microbiology ; *Microbiota ; *Colitis, Ulcerative/surgery ; Butyrates/analysis ; }, abstract = {BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the standard of care after total proctocolectomy for ulcerative colitis (UC). Around 50% of patients will experience pouchitis, an idiopathic inflammatory condition. Antibiotics are the backbone of treatment of pouchitis; however, antibiotic-resistant pouchitis develops in 5-10% of those patients. It has been shown that fecal microbiota transplantation (FMT) is an effective treatment for UC, but results for FMT antibiotic-resistant pouchitis are inconsistent.<br><br>METHODS: To uncover which metabolic activities were transferred to the recipients during FMT and helped the remission, we performed a longitudinal case study of the gut metatranscriptomes from three patients and their donors. The patients were treated by two to three FMTs, and stool samples were analyzed for up to 140&#xa0;days.<br><br>RESULTS: Reduced expression in pouchitis patients compared to healthy donors was observed for genes involved in biosynthesis of amino acids, cofactors, and B vitamins. An independent metatranscriptome dataset of UC patients showed a similar result. Other functions including biosynthesis of butyrate, metabolism of bile acids, and tryptophan were also much lower expressed in pouchitis. After FMT, these activities transiently increased, and the overall metatranscriptome profiles closely mirrored those of the respective donors with notable fluctuations during the subsequent weeks. The levels of the clinical marker fecal calprotectin were concordant with the metatranscriptome data. Faecalibacterium prausnitzii represented the most active species contributing to butyrate synthesis via the acetyl-CoA pathway. Remission occurred after the last FMT in all patients and was characterized by a microbiota activity profile distinct from donors in two of the patients.<br><br>CONCLUSIONS: Our study demonstrates the clear but short-lived activity engraftment of donor microbiota, particularly the butyrate biosynthesis after each FMT. The data suggest that FMT triggers shifts in the activity of patient microbiota towards health which need to be repeated to reach critical thresholds. As a case study, these insights warrant cautious interpretation, and validation in larger cohorts is necessary for generalized applications. In the long run, probiotics with high taxonomic diversity consisting of well characterized strains could replace FMT to avoid the costly screening of donors and the risk of transferring unwanted genetic material. Video Abstract.}, }
@article {pmid38036190, year = {2024}, author = {Cai, X and Li, Z and Yao, Y and Zheng, Y and Zhang, M and Ye, Y}, title = {Glycolithocholic acid increases the frequency of circulating Tregs through constitutive androstane receptor to alleviate postmenopausal osteoporosis.}, journal = {Biochemical pharmacology}, volume = {219}, number = {}, pages = {115951}, doi = {10.1016/j.bcp.2023.115951}, pmid = {38036190}, issn = {1873-2968}, mesh = {Humans ; Female ; Rats ; Animals ; *Osteoporosis, Postmenopausal/drug therapy/genetics ; Osteogenesis ; Constitutive Androstane Receptor ; Cell Differentiation ; }, abstract = {BACKGROUND AND PURPOSE: Gut microbiota and their metabolic activity are important regulators of host immunity. However, the role of gut microbiota and their metabolic activity-mediated osteoimmunity in postmenopausal osteoporosis (PMO) remains unknown. This study aimed to explore the role of gut microbiota and their metabolic activity in PMO.<br><br>EXPERIMENTAL APPROACH: 16S rDNA sequencing was used for analyzing the gut microbiota diversity of patients with PMO and rat models, and a targeted metabolism study was performed for analyzing metabolite levels. Flow cytometry was used for analyzing the frequency of immune cells. Micro-CT was used for analyzing bone damage in rat models. Fecal microbiota transplantation was performed for exploring the therapeutic effect of the gut microbiota on PMO. CD4[+] T cells were co-cultured with bone marrow mesenchymal stem cells for evaluating their molecular mechanisms.<br><br>KEY RESULTS: Patients with PMO exhibited reduced gut microbiota diversity, and fecal glycolithocholic acid (GLCA) levels correlated with the degree of osteoporosis. GLCA levels in the gut were positively correlated with the frequency of circulating Tregs in ovariectomized rats. Restoration of the gut microbiota alleviated osteoporosis in ovariectomized rats. Circulating GLCA augmented CD4[+] T cell differentiation into Tregs via constitutive androstane receptors. The increased frequency of Tregs further promoted the osteogenic differentiation of bone marrow mesenchymal stem cells to alleviate osteoporosis.<br><br>CONCLUSION AND IMPLICATIONS: GLCA alleviated PMO by increasing the frequency of circulating Tregs, acting via the constitutive androstane receptor. This study reveals a new strategy for the treatment of PMO, with GLCA as a potential drug candidate.}, }
@article {pmid38035338, year = {2023}, author = {Van Dingenen, L and Segers, C and Wouters, S and Mysara, M and Leys, N and Kumar-Singh, S and Malhotra-Kumar, S and Van Houdt, R}, title = {Dissecting the role of the gut microbiome and fecal microbiota transplantation in radio- and immunotherapy treatment of colorectal cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1298264}, pmid = {38035338}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Immunotherapy ; *Colorectal Neoplasms/therapy ; }, abstract = {Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and poses a major burden on the human health worldwide. At the moment, treatment of CRC consists of surgery in combination with (neo)adjuvant chemotherapy and/or radiotherapy. More recently, immune checkpoint blockers (ICBs) have also been approved for CRC treatment. In addition, recent studies have shown that radiotherapy and ICBs act synergistically, with radiotherapy stimulating the immune system that is activated by ICBs. However, both treatments are also associated with severe toxicity and efficacy issues, which can lead to temporary or permanent discontinuation of these treatment programs. There's growing evidence pointing to the gut microbiome playing a role in these issues. Some microorganisms seem to contribute to radiotherapy-associated toxicity and hinder ICB efficacy, while others seem to reduce radiotherapy-associated toxicity or enhance ICB efficacy. Consequently, fecal microbiota transplantation (FMT) has been applied to reduce radio- and immunotherapy-related toxicity and enhance their efficacies. Here, we have reviewed the currently available preclinical and clinical data in CRC treatment, with a focus on how the gut microbiome influences radio- and immunotherapy toxicity and efficacy and if these treatments could benefit from FMT.}, }
@article {pmid38035329, year = {2023}, author = {Mbaye, B and Magdy Wasfy, R and Borentain, P and Tidjani Alou, M and Mottola, G and Bossi, V and Caputo, A and Gerolami, R and Million, M}, title = {Increased fecal ethanol and enriched ethanol-producing gut bacteria Limosilactobacillus fermentum, Enterocloster bolteae, Mediterraneibacter gnavus and Streptococcus mutans in nonalcoholic steatohepatitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1279354}, pmid = {38035329}, issn = {2235-2988}, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/etiology ; Ethanol ; Streptococcus mutans/genetics ; *Limosilactobacillus fermentum ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; Glucose ; Cholesterol ; }, abstract = {BACKGROUND: Non-alcoholic steatohepatitis (NASH) has become a major public health issue as one of the leading causes of liver disease and transplantation worldwide. The instrumental role of the gut microbiota is emerging but still under investigation. Endogenous ethanol (EtOH) production by gut bacteria and yeasts is an emerging putative mechanism. Microbial metagenomics and culture studies targeting enterobacteria or yeasts have been reported, but no culturomics studies have been conducted so far.<br><br>AIM: To assess fecal EtOH and other biochemical parameters, characterize NASH-associated dysbiosis and identify EtOH-producing gut microbes associated with the disease, fecal samples from 41 NASH patients and 24 controls were analyzed. High-performance liquid chromatography (HPLC) was used for EtOH, glucose, total proteins, triglyceride and total cholesterol. Viable bacteria were assessed with microbial culturomics. Microbial genetic material was assessed using 16S metagenomics targeting the hypervariable V3V4 region.<br><br>RESULTS: Fecal EtOH and glucose was elevated in the stools of NASH patients (p < 0.05) but not triglyceride, total cholesterol or proteins. In culturomics, EtOH-producing Enterocloster bolteae and Limosilactobacillus fermentum were enriched in NASH. V3V4 16S rRNA amplicon sequencing confirmed the enrichment in EtOH-producing bacteria including L. fermentum, Mediterraneibacter gnavus and Streptococcus mutans, species previously associated with NASH and other dysbiosis-associated diseases. Strikingly, E. bolteae was identified only by culturomics. The well-known Lacticaseibacillus casei was identified in controls but never isolated in patients with NASH (p < 0.05).<br><br>CONCLUSION: Elevated fecal EtOH and glucose is a feature of NASH. Several different EtOH-producing gut bacteria may play an instrumental role in the disease. Culturomics and metagenomics, two complementary methods, will be critical to identify EtOH-producing bacteria for future diagnostic markers and therapeutic targets for NASH. Suppression of EtOH-producing gut microbes and L. casei administration are options to be tested in NASH treatment.}, }
@article {pmid38035162, year = {2023}, author = {Yuan, QF and Wu, HY and Chen, XY and Zheng, YM and Fu, SL and Wang, XH and Zhu, JW and Guo, JD and He, XX and Wu, LH}, title = {Colonic Endoscopic Tubing Is Safe and Effective Approach for Washed Microbiota Transplantation in Autistic Children.}, journal = {Gastroenterology research and practice}, volume = {2023}, number = {}, pages = {7838601}, pmid = {38035162}, issn = {1687-6121}, abstract = {BACKGROUND: Washed microbiota transplantation (WMT) as the improved methods of fecal microbiota transplantation has been employed as a therapeutic approach for ameliorating symptoms associated with autism spectrum disorder (ASD). In this context, colonic transendoscopic enteral tubing (TET) has been utilized as a novel procedure for administering WMT.<br><br>METHODS: Data of children with ASD who received WMT by TET were retrospectively reviewed, including bowel preparation methods, TET operation time, success rate, tube retention time, the comfort of children, adverse events, and parent satisfaction.<br><br>RESULTS: A total of 38 participants underwent 124 colonic TET catheterization procedures. The average time of TET operation was 15 minutes, and the success rate was 100% (124/124). There was no significant difference in TET operation time between high-seniority physicians and low-seniority physicians. In 123 procedures (99%), the TET tube allowed the completion of WMT treatment for 6 consecutive days. In 118 procedures (95.2%), the tube was detached spontaneously after the end of the treatment course, and the average TET tube retention time was 8 days. There was no incidence of tube blockage during the treatment course. No severe adverse events occurred during follow-up. Parents of all participants reported a high level of satisfaction with TET.<br><br>CONCLUSION: Colonic TET is a safe and feasible method for WMT in children with ASD.}, }
@article {pmid38034098, year = {2023}, author = {Bai, M and Guo, H and Zheng, XY}, title = {Inflammatory bowel disease and Clostridium difficile infection: clinical presentation, diagnosis, and management.}, journal = {Therapeutic advances in gastroenterology}, volume = {16}, number = {}, pages = {17562848231207280}, pmid = {38034098}, issn = {1756-283X}, abstract = {As a frequent complication of inflammatory bowel disease (IBD), Clostridium difficile infection (CDI) was confirmed to not only aggravate the symptoms of IBD but also result in unexpected outcomes, including death. With the increasing prevalence rate of IBD and the updating of CDI diagnosis, the incidence of CDI in IBD patients is also seen rising. Although a detection method consisting of glutamate dehydrogenase immunoassay or nucleic acid amplification test and then toxin A/B enzyme immunoassay was recommended and widely adopted, the diagnosis of CDI in IBD is still a challenge because of the overlap between the symptoms of CDI in IBD and CDI itself. Vancomycin and fidaxomicin are the first-line therapy for CDI in IBD; however, the treatment has different effects due to the complexity of IBD patients' conditions and the choice of different treatment schemes. Although the use of fecal microbial transplantation is now in the ascendant for IBD management, the prospects are still uncertain and the prevention and treatment of the recurrence of CDI in IBD remain a clinical challenge. In this paper, the epidemiology, pathophysiology, clinical manifestation, prevention, and therapy of CDI in IBD were summarized and presented.}, }
@article {pmid38034050, year = {2023}, author = {Chang, TE and Lee, KC and Lee, PC and Wang, YP and Lin, YT and Huang, HC and Luo, JC and Ho, HL and Huang, YH and Hou, MC and , }, title = {Assuring safety of fecal microbiota transplantation in the COVID-19 era: A single-center experience.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {7}, number = {11}, pages = {765-771}, pmid = {38034050}, issn = {2397-9070}, abstract = {BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) is used to treat recurrent or refractory Clostridioides difficile infection (CDI). In the past, screening of fecal donors required surveillance of personal behavior, medical history, and diseases that could be transmitted by the blood or fecal-oral route. In addition, the exclusion of multidrug-resistant organisms (MDROs) has been recommended since 2018. This task has become more complicated in the era of the coronavirus disease-2019 (COVID-19) pandemic. To prevent fecal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is crucial to commence screening for SARS-CoV-2, alongside other traditional tests. Our aim was to investigate whether hidden carriers of SARS-CoV-2 were enrolled for stool donation, and the status of the presence or incidence of MDRO during fecal donation in Taiwan.<br><br>METHODS: Fecal products collected from March 2019 to December 2022 were tested for MDRO and nucleic acid amplification tests for SARS-CoV-2 using the pooling method. The period of fecal product collection crossed the time before and during the COVID pandemic in Taiwan.<br><br>RESULTS: A total of 151 fecal samples were collected. The fecal products were tested using polymerase chain reaction (PCR) to detect SARS-CoV-2. The results were negative for all stocks. This was similar to the results of MDRO testing. The safety of FMT products has been guaranteed during the pandemic.<br><br>CONCLUSION: Our FMT center produced MDRO-free and COVID-19-free products before and during the COVID-19 outbreak in Taiwan. Our protocol was effective for ensuring the safety of FMT products.}, }
@article {pmid38033573, year = {2023}, author = {Zhu, Q and Wu, K and Yang, Q and Meng, B and Niu, Y and Zhao, F}, title = {Advances in psoriasis and gut microorganisms with co-metabolites.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1192543}, pmid = {38033573}, issn = {1664-302X}, abstract = {This review summarizes the potential role of gut microbes and their metabolites as novel mediators of psoriasis, including their composition and function in disease pathogenesis, progression, and management. Gut microbiota network analysis, colony construction, and in vivo large-scale interaction experiments showed that different degrees of damage and repair in psoriasis, both in animals and humans, involve cross-border homeostasis of the microbial community. Which gut microbiota interactions are present in psoriasis and how they collaborate with immune cells and influence psoriasis development via the gut-skin axis remain incompletely elucidated. In this article, we review the latest information on the unique patterns of gut microbiota and co-metabolites involved in the pathogenesis of psoriasis and attempt to explore microbial-based therapeutic targets derived from mono-and polymicrobial probiotics, fecal microbiota transplantation, pharmacomicrobiomics, and dietary interventions as diagnostic or therapeutic approaches promising to provide new options and long-term management for psoriasis.}, }
@article {pmid38033557, year = {2023}, author = {Xiang, W and Xiang, H and Wang, J and Jiang, Y and Pan, C and Ji, B and Zhang, A}, title = {Fecal microbiota transplantation: a novel strategy for treating Alzheimer's disease.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1281233}, pmid = {38033557}, issn = {1664-302X}, abstract = {Alzheimer's disease is a common neurological disorder, which has become one of the major factors affecting human health due to its serious impact on individuals, families and society. It has been confirmed that gut microbiota can affect the occurrence and development of Alzheimer's disease. Especially, fecal microbiota transplantation plays a positive role in the treatment of Alzheimer's disease. The mechanisms for improving Alzheimer's disease might include anti-inflammation and regulation of amyloid β-protein, synaptic plasticity, short-chain fatty acids, and histone acetylation. In this mini-review, the relationship between fecal microbiota transplantation and Alzheimer's disease was summarized. It is hoped that fecal microbiota transplantation would play a positive role in the prevention and treatment of Alzheimer's disease in the future.}, }
@article {pmid38031252, year = {2023}, author = {Crossland, NA and Beck, S and Tan, WY and Lo, M and Mason, JB and Zhang, C and Guo, W and Crott, JW}, title = {Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2288187}, pmid = {38031252}, issn = {1949-0984}, support = {R03 CA234999/CA/NCI NIH HHS/United States ; S10 OD026983/OD/NIH HHS/United States ; S10 OD030269/OD/NIH HHS/United States ; S10 OD032203/OD/NIH HHS/United States ; }, mesh = {Mice ; Animals ; Azoxymethane/toxicity ; *Gastrointestinal Microbiome ; *Microbiota ; Fecal Microbiota Transplantation ; *Colonic Neoplasms ; Inflammation ; Carcinogenesis ; Cell Proliferation ; }, abstract = {Aging is a strong risk factor for colorectal cancer (CRC). It is well established that gut microbial dysbiosis can play a role in the etiology of CRC. Although the composition of the gut microbial community changes with age and is reported to become more pro-inflammatory, it is unclear whether such changes are also pro-tumorigenic for the colon. To address this gap, we conducted fecal microbiota transplants (FMT) from young (DY, ~6 wk) and old (DO, ~72 wk) donor mice into young (8 wk) recipient mice that were pre-treated with antibiotics. After initiating tumorigenesis with azoxymethane, recipients were maintained for 19 wk during which time they received monthly FMT boosters. Compared to recipients of young donors (RY), recipients of old donors (RO) had an approximately 3-fold higher prevalence of histologically confirmed colon tumors (15.8 vs 50%, Chi2 P = .03), approximately 2-fold higher proliferating colonocytes as well as significantly elevated colonic IL-6, IL-1β and Tnf-α. Transcriptomics analysis of the colonic mucosa revealed a striking upregulation of mitochondria-related genes in the RO mice, a finding corroborated by increased mitochondrial abundance. Amongst the differences in fecal microbiome observed between DY and DO mice, the genera Ruminoclostridium, Lachnoclostridium and Marvinbryantia were more abundant in DY mice while the genera Bacteroides and Akkermansia were more abundant in DO mice. Amongst recipients, Ruminoclostridium and Lachnoclostridium were higher in RY mice while Bacteroides was higher in RO mice. Differences in fecal microbiota were observed between young and old mice, some of which persisted upon transplant into recipient mice. Recipients of old donors displayed significantly higher colonic proliferation, inflammation and tumor abundance compared to recipients of young donors. These findings support an etiological role for altered gut microbial communities in the increased risk for CRC with increasing age and establishes that such risk can be transmitted between individuals.}, }
@article {pmid38030980, year = {2023}, author = {Liu, H and Li, J and Yuan, J and Huang, J and Xu, Y}, title = {Fecal microbiota transplantation as a therapy for treating ulcerative colitis: an overview of systematic reviews.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {371}, pmid = {38030980}, issn = {1471-2180}, mesh = {Humans ; *Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation/adverse effects ; Systematic Reviews as Topic ; }, abstract = {AIM: The current overview on published systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically gather, evaluate, and synthesize solid evidence for using fecal microbiota transplantation (FMT) to treat ulcerative colitis (UC).<br><br>METHODS: Relevant articles published before January 2023 were collected from Web of Science, Embase, PubMed, and Cochrane Library. Two authors used Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, PRISMA checklists, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system were applied by two authors to independently evaluate the methodological quality, reporting quality, and evidence quality, respectively. Re-meta-analysis on the primary RCTs was conducted after excluding overlapping randomized controlled trials (RCTs).<br><br>RESULTS: Six SRs/MAs involving 12 primary RCTs and 544 participants were included. According to the AMSTAR-2 tool and PRISMA checklist, methodological quality and reporting quality of the included studies was overall satisfactory. The evidence quality of a great majority of outcomes was rated as moderate to high according to the GRADE system. Compared to placebo, the re-meta-analysis found a great advantage of use FMT in inducing combined clinical and endoscopic remission (OR 3.83 [2.31, 6.34]), clinical remission (3.31 [2.09, 5.25]), endoscopic remission (OR 3.75 [2.20, 6.39]), clinical response (OR 2.56 [1.64, 4.00]), and endoscopic response (OR 2.18 [1.12, 4.26]). Pooled data showed no significant difference in serious adverse events between patients receiving FMT and those receiving placebo (OR 1.53 [0.74, 3.19]). Evidence quality of the outcomes derived from re-meta-analysis was significantly higher after overcoming the limitations of previous SRs/MAs.<br><br>CONCLUSION: In conclusion, moderate- to high-quality evidence supported a promising use of FMT to safely induce remission in UC. However, further trials with larger sample size are still required to comprehensively analyze the delivery route, total dosage, frequency, and donor selection in FMT.}, }
@article {pmid38030463, year = {2024}, author = {Catalán, V and Gómez-Ambrosi, J}, title = {Will the manipulation of the gut microbiota be effective for the treatment of metabolic diseases?.}, journal = {European journal of internal medicine}, volume = {119}, number = {}, pages = {36-38}, doi = {10.1016/j.ejim.2023.11.025}, pmid = {38030463}, issn = {1879-0828}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Metabolic Diseases/therapy ; Gastrointestinal Tract ; *Probiotics ; }, }
@article {pmid38030048, year = {2024}, author = {Gong, X and Ma, Y and Deng, X and Li, A and Li, X and Kong, X and Liu, Y and Liu, X and Guo, K and Yang, Y and Li, Z and Wei, H and Zhou, D and Hong, Z}, title = {Intestinal dysbiosis exacerbates susceptibility to the anti-NMDA receptor encephalitis-like phenotype by changing blood brain barrier permeability and immune homeostasis.}, journal = {Brain, behavior, and immunity}, volume = {116}, number = {}, pages = {34-51}, doi = {10.1016/j.bbi.2023.11.030}, pmid = {38030048}, issn = {1090-2139}, mesh = {Humans ; Mice ; Animals ; *Anti-N-Methyl-D-Aspartate Receptor Encephalitis ; Blood-Brain Barrier ; Dysbiosis ; Homeostasis ; Permeability ; }, abstract = {Changes in the intestinal microbiota have been observed in patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE). However, whether and how the intestinal microbiota is involved in the pathogenesis of NMDARE susceptibility needs to be demonstrated. Here, we first showed that germ-free (GF) mice that underwent fecal microbiota transplantation (FMT) from NMDARE patients, whose fecal microbiota exhibited low short-chain fatty acid content, decreased abundance of Lachnospiraceae, and increased abundance of Verrucomicrobiota, Akkermansia, Parabacteroides, Oscillospirales, showed significant behavioral deficits. Then, these FMT mice were actively immunized with an amino terminal domain peptide from the GluN1 subunit (GluN1356-385) to mimic the pathogenic process of NMDARE. We found that FMT mice showed an increased susceptibility to an encephalitis-like phenotype characterized by more clinical symptoms, greater pentazole (PTZ)-induced susceptibility to seizures, and higher levels of T2 weighted image (T2WI) hyperintensities following immunization. Furthermore, mice with dysbiotic microbiota had impaired blood-brain barrier integrity and a proinflammatory condition. In NMDARE-microbiota recipient mice, the levels of Evan's blue (EB) dye extravasation increased, ZO-1 and claudin-5 expression decreased, and the levels of proinflammatory cytokines (IL-1, IL-6, IL-17, TNF-α and LPS) increased. Finally, significant brain inflammation, mainly in hippocampal and cortical regions, with modest neuroinflammation, immune cell infiltration, and reduced expression of NMDA receptors were observed in NMDARE microbiota recipient mice following immunization. Overall, our findings demonstrated that intestinal dysbiosis increased NMDARE susceptibility, suggesting a new target for limiting the occurrence of the severe phenotype of NMDARE.}, }
@article {pmid38029942, year = {2024}, author = {Xie, Z and Zhou, J and Zhang, X and Li, Z}, title = {Clinical potential of microbiota in thyroid cancer therapy.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1870}, number = {2}, pages = {166971}, doi = {10.1016/j.bbadis.2023.166971}, pmid = {38029942}, issn = {1879-260X}, mesh = {Humans ; Iodine Radioisotopes ; Quality of Life ; *Thyroid Neoplasms/therapy ; *Microbiota ; }, abstract = {Thyroid cancer is one of the most common tumors of the endocrine system because of its rapid and steady increase in incidence and prevalence. In recent years, a growing number of studies have identified a key role for the gut, thyroid tissue and oral microbiota in the regulation of metabolism and the immune system. A growing body of evidence has conclusively demonstrated that the microbiota influences tumor formation, prevention, diagnosis, and treatment. We provide extensive information in which oral, gut, and thyroid microbiota have an effect on thyroid cancer development in this review. In addition, we thoroughly discuss the various microbiota species, their potential functions, and the underlying mechanisms for thyroid cancer. The microbiome offers a unique opportunity to improve the effectiveness of immunotherapy and radioiodine therapy thyroid cancer by maintaining the right type of microbiota, and holds great promise for improving clinical outcomes and quality of life for thyroid cancer patients.}, }
@article {pmid38029189, year = {2023}, author = {Zhang, X and Luo, X and Tian, L and Yue, P and Li, M and Liu, K and Zhu, D and Huang, C and Shi, Q and Yang, L and Xia, Z and Zhao, J and Ma, Z and Li, J and Leung, JW and Lin, Y and Yuan, J and Meng, W and Li, X and Chen, Y}, title = {The gut microbiome dysbiosis and regulation by fecal microbiota transplantation: umbrella review.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1286429}, pmid = {38029189}, issn = {1664-302X}, abstract = {BACKGROUND: Gut microbiome dysbiosis has been implicated in various gastrointestinal and extra-gastrointestinal diseases, but evidence on the efficacy and safety of fecal microbiota transplantation (FMT) for therapeutic indications remains unclear.<br><br>METHODS: The gutMDisorder database was used to summarize the associations between gut microbiome dysbiosis and diseases. We performed an umbrella review of published meta-analyses to determine the evidence synthesis on the efficacy and safety of FMT in treating various diseases. Our study was registered in PROSPERO (CRD42022301226).<br><br>RESULTS: Gut microbiome dysbiosis was associated with 117 gastrointestinal and extra-gastrointestinal. Colorectal cancer was associated with 92 dysbiosis. Dysbiosis involving Firmicutes (phylum) was associated with 34 diseases. We identified 62 published meta-analyses of FMT. FMT was found to be effective for 13 diseases, with a 95.56% cure rate (95% CI: 93.88-97.05%) for recurrent Chloridoids difficile infection (rCDI). Evidence was high quality for rCDI and moderate to high quality for ulcerative colitis and Crohn's disease but low to very low quality for other diseases.<br><br>CONCLUSION: Gut microbiome dysbiosis may be implicated in numerous diseases. Substantial evidence suggests FMT improves clinical outcomes for certain indications, but evidence quality varies greatly depending on the specific indication, route of administration, frequency of instillation, fecal preparation, and donor type. This variability should inform clinical, policy, and implementation decisions regarding FMT.}, }
@article {pmid38025767, year = {2023}, author = {Sun, H and Su, X and Liu, Y and Li, G and Du, Q}, title = {Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats.}, journal = {iScience}, volume = {26}, number = {12}, pages = {108392}, pmid = {38025767}, issn = {2589-0042}, abstract = {Previous research has demonstrated significant differences in intestinal flora between pregnant women with intrahepatic cholestasis of pregnancy (ICP) and healthy pregnant women. The objective of our study is to identify the key bacteria involved in ICP rats and explore the underlying mechanism. We established an ICP rat model and collected rat feces for metagenomic sequencing and found that Roseburia intestinalis (R.I) is the key bacteria in ICP. Transplantation of R.I improved phenotypes associated with ICP through the bile acid/farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) signaling pathway. We used the FXR antagonist Z-Guggulsterone (Z-Gu) to verify the key role of FXR in ICP and found that Z-Gu reversed the benefits of R.I on ICP rats. Our research highlights the important role of intestinal flora in the pathogenesis of ICP and provides a novel approach for its treatment.}, }
@article {pmid38024855, year = {2023}, author = {Mao, Z and Hui, H and Zhao, X and Xu, L and Qi, Y and Yin, L and Qu, L and Han, L and Peng, J}, title = {Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling.}, journal = {Journal of pharmaceutical analysis}, volume = {13}, number = {10}, pages = {1153-1167}, pmid = {38024855}, issn = {2214-0883}, abstract = {It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease (PD). Dioscin, a bioactive steroidal saponin, shows various activities. However, its effects and mechanisms against PD are limited. In this study, dioscin dramatically alleviated neuroinflammation and oxidative stress, and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus, Streptococcus, Bacteroides and Lactobacillus genera, which further inhibited bile salt hydrolase (BSH) activity and blocked bile acid (BA) deconjugation. Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent. In addition, non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis. Moreover, targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid and β-muricholic acid in feces and serum. In addition, ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice. Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5 (TGR5), glucagon-like peptide-1 receptor (GLP-1R), GLP-1, superoxide dismutase (SOD), and down-regulated NADPH oxidases 2 (NOX2) and nuclear factor-kappaB (NF-κB) levels. Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice, suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.}, }
@article {pmid38024475, year = {2023}, author = {Zhao, W and Lei, J and Ke, S and Chen, Y and Xiao, J and Tang, Z and Wang, L and Ren, Y and Alnaggar, M and Qiu, H and Shi, W and Yin, L and Chen, Y}, title = {Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215).}, journal = {EClinicalMedicine}, volume = {66}, number = {}, pages = {102315}, pmid = {38024475}, issn = {2589-5370}, abstract = {BACKGROUND: Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1 inhibitors. Antiangiogenic therapy can enhance anti-PD-1 efficacy, but it still cannot meet clinical needs. Increasing evidence supported a close relationship between gut microbiome and anti-PD-1 efficacy. This study aimed to explore the efficacy and safety of the combination of fecal microbiota transplantation (FMT) and tislelizumab and fruquintinib in refractory MSS mCRC.<br><br>METHODS: In the phase II trial, MSS mCRC patients were administered FMT plus tislelizumab and fruquintinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), clinical benefit rate (CBR), safety and quality of life. Feces and peripheral blood were collected for exploratory biomarker analysis. This study is registered with Chictr.org.cn, identifier ChiCTR2100046768.<br><br>FINDINGS: From May 10, 2021 to January 17, 2022, 20 patients were enrolled. Median follow-up was 13.7 months. Median PFS was 9.6 months (95% CI 4.1-15.1). Median OS was 13.7 months (95% CI 9.3-17.7). Median DoR was 8.1 months (95% CI 1.7-10.6). ORR was 20% (95% CI 5.7-43.7). DCR was 95% (95% CI 75.1-99.9). CBR was 60% (95% CI 36.1-80.9). Nineteen patients (95%) experienced at least one treatment-related adverse event (TRAE). Six patients (30%) had grade 3-4 TRAEs, with the most common being albuminuria (10%), urine occult blood (10%), fecal occult blood (10%), hypertension (5%), hyperglycemia (5%), liver dysfunction (5%), hand-foot skin reaction (5%), and hypothyroidism (5%). No treatment-related deaths occurred. Responders had a high-abundance of Proteobacteria and Lachnospiraceae family and a low-abundance of Actinobacteriota and Bifidobacterium. The treatment did not change the structure of peripheral blood TCR repertoire. However, the expanded TCRs exhibited the characteristics of antigen-driven responses in responders.<br><br>INTERPRETATION: FMT plus tislelizumab and fruquintinib as third-line or above treatment showed improved survival and manageable safety in refractory MSS mCRC, suggesting a valuable new treatment option for this patient population.<br><br>FUNDING: This study was supported by the National Natural Science Foundation of China (82102954 to Wensi Zhao) and the Special Project of Central Government for Local Science and Technology Development of Hubei Province (ZYYD2020000169 to Yongshun Chen).}, }
@article {pmid38022314, year = {2023}, author = {Sharifa, M and Ghosh, T and Daher, OA and Bhusal, P and Alaameri, YA and Naz, J and Ekhator, C and Bellegarde, SB and Bisharat, P and Vaghani, V and Hussain, A}, title = {Unraveling the Gut-Brain Axis in Multiple Sclerosis: Exploring Dysbiosis, Oxidative Stress, and Therapeutic Insights.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e47058}, pmid = {38022314}, issn = {2168-8184}, abstract = {This comprehensive review delves into the intricate relationship between the gut microbiota and multiple sclerosis (MS), shedding light on the potential therapeutic avenues for this complex autoimmune disease. It emphasizes the multifactorial nature of MS, including genetic, environmental, and gender-related factors. Furthermore, the article highlights the emerging role of gut microbiota in MS pathophysiology, particularly in terms of gut dysbiosis, oxidative stress, and inflammasome activation within the gut-brain axis. This interplay raises intriguing questions about how the gut microbiota influences the onset and progression of MS. Environmental factors, such as diet and pollutants, add further layers of complexity to the connection between gut health and MS risk. This review also discusses promising therapeutic interventions, such as fecal microbiota transplantation, probiotics, dietary adjustments, and gut-derived metabolites that offer potential avenues for managing MS. It underscores the need for ongoing research to fully unravel the complexities of the role of the gut-brain axis in MS. Ultimately, this article provides a comprehensive exploration of the topic, offering hope for novel preventive and therapeutic strategies that could significantly improve the lives of individuals affected by this challenging autoimmune condition.}, }
@article {pmid38021361, year = {2023}, author = {Sehgal, K and Feuerstadt, P}, title = {The real efficacy of microbiota restoration following standard of care antimicrobial in patients with recurrent Clostridiodes difficile.}, journal = {Translational gastroenterology and hepatology}, volume = {8}, number = {}, pages = {31}, pmid = {38021361}, issn = {2415-1289}, }
@article {pmid38019088, year = {2024}, author = {Feuerstadt, P and Crawford, CV and Tan, X and Pokhilko, V and Bancke, L and Ng, S and Guthmueller, B and Bidell, MR and Tillotson, G and Johnson, S and Skinner, AM}, title = {Fecal Microbiota, Live-jslm for the Prevention of Recurrent Clostridioides difficile Infection : Subgroup Analysis of PUNCH CD2 and PUNCH CD3.}, journal = {Journal of clinical gastroenterology}, volume = {58}, number = {8}, pages = {818-824}, pmid = {38019088}, issn = {1539-2031}, support = {IK2 BX005609/BX/BLRD VA/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Anti-Bacterial Agents/administration &amp; dosage/adverse effects ; Bayes Theorem ; *Clostridioides difficile/isolation &amp; purification ; *Clostridium Infections/prevention &amp; control/microbiology ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Recurrence ; Risk Factors ; Secondary Prevention/methods ; Treatment Outcome ; Vancomycin/administration &amp; dosage/therapeutic use ; }, abstract = {GOALS: To assess fecal microbiota, live-jslm (REBYOTA, abbreviated as RBL, formerly RBX2660) efficacy and safety in participants grouped by recurrent Clostridioides difficile infection (rCDI) risk factors and treatment-related variables.<br><br>BACKGROUND: RBL is the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration for the prevention of rCDI in adults after antibiotic treatment for rCDI.<br><br>STUDY: Treatment success rates across subgroups for PUNCH CD3 (NCT03244644) were estimated using a Bayesian hierarchical model, borrowing data from PUNCH CD2 (NCT02299570). Treatment-emergent adverse events were summarized for the double-blind treatment period within 8 weeks.<br><br>RESULTS: Treatment differences between RBL and placebo at 8 weeks were similar to the total population for most subgroups. Treatment effect sizes were similar between CDI tests, higher for oral vancomycin courses >14 days versus &#x2264;14 days and higher for antibiotic washout periods of 3 days versus &#x2264;2 days. The largest reductions in the rate of rCDI with RBL versus placebo were observed for participants with a 3-day CDI antibiotic washout period and participants with &#x2265;4 previous CDI episodes. Most RBL-treated participants experienced TEAEs that were mild or moderate in severity and related to preexisting conditions.<br><br>CONCLUSION: This analysis provides further evidence of RBL efficacy and safety across subgroups, including those at high risk for rCDI.}, }
@article {pmid38018424, year = {2023}, author = {Hu, S and Zhao, R and Xu, Y and Gu, Z and Zhu, B and Hu, J}, title = {Orally-administered nanomedicine systems targeting colon inflammation for the treatment of inflammatory bowel disease: latest advances.}, journal = {Journal of materials chemistry. B}, volume = {12}, number = {1}, pages = {13-38}, doi = {10.1039/d3tb02302h}, pmid = {38018424}, issn = {2050-7518}, mesh = {Humans ; Drug Delivery Systems/methods ; Nanomedicine ; *Inflammatory Bowel Diseases/drug therapy/metabolism ; *Colitis, Ulcerative/drug therapy ; Inflammation/drug therapy ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic and idiopathic condition that results in inflammation of the gastrointestinal tract, leading to conditions such as ulcerative colitis and Crohn's disease. Commonly used treatments for IBD include anti-inflammatory drugs, immunosuppressants, and antibiotics. Fecal microbiota transplantation is also being explored as a potential treatment method; however, these drugs may lead to systemic side effects. Oral administration is preferred for IBD treatment, but accurately locating the inflamed area in the colon is challenging due to multiple physiological barriers. Nanoparticle drug delivery systems possess unique physicochemical properties that enable precise delivery to the target site for IBD treatment, exploiting the increased permeability and retention effect of inflamed intestines. The first part of this review comprehensively introduces the pathophysiological environment of IBD, covering the gastrointestinal pH, various enzymes in the pathway, transport time, intestinal mucus, intestinal epithelium, intestinal immune cells, and intestinal microbiota. The second part focuses on the latest advances in the mechanism and strategies of targeted delivery using oral nanoparticle drug delivery systems for colitis-related fields. Finally, we present challenges and potential directions for future IBD treatment with the assistance of nanotechnology.}, }
@article {pmid38018317, year = {2024}, author = {Xiao, Y and Feng, J and Jia, J and Li, J and Zhou, Y and Song, Z and Guan, F and Li, X and Liu, L}, title = {Vitamin K1 ameliorates lipopolysaccharide-triggered skeletal muscle damage revealed by faecal bacteria transplantation.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {15}, number = {1}, pages = {81-97}, pmid = {38018317}, issn = {2190-6009}, support = {2022YFS0632//Sichuan Provincial Science and Technology Plan Joint Innovation Projects/ ; }, mesh = {Humans ; Mice ; Animals ; *Fecal Microbiota Transplantation ; Lipopolysaccharides/adverse effects ; Sirtuin 1 ; Vitamin K 1/adverse effects ; Inflammation ; *Sepsis ; Muscle, Skeletal ; Muscle Weakness ; }, abstract = {BACKGROUND: Sepsis-associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis-induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis-associated muscle weakness.<br><br>METHODS: In a lipopolysaccharide (LPS)-induced inflammation mouse model, mice with different sensitivities to LPS-induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS-triggered muscle damage was investigated, and the underlying mechanism was explored.<br><br>RESULTS: Recipients exhibited varying LPS-triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF-1 (0.825&#xa0;&#xb1;&#xa0;0.063 vs. 0.304&#xa0;&#xb1;&#xa0;0.293, P&#xa0;=&#xa0;0.0141) and MAFbx (1.055&#xa0;&#xb1;&#xa0;0.079 vs. 0.456&#xa0;&#xb1;&#xa0;0.3, P&#xa0;=&#xa0;0.0092). Colonic tight junction proteins ZO-1 (0.550&#xa0;&#xb1;&#xa0;0.087 vs. 0.842&#xa0;&#xb1;&#xa0;0.094, P&#xa0;=&#xa0;0.0492) and occludin (0.284&#xa0;&#xb1;&#xa0;0.057 vs. 0.664&#xa0;&#xb1;&#xa0;0.191, P&#xa0;=&#xa0;0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P&#xa0;=&#xa0;0.0195) and serum of the Res group (P&#xa0;=&#xa0;0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy-related protein expression downregulated (P&#xa0;<&#xa0;0.05). Meanwhile SIRT1 protein expression were upregulated (0.320&#xa0;&#xb1;&#xa0;0.035 vs. 0.685&#xa0;&#xb1;&#xa0;0.081, P&#xa0;=&#xa0;0.0281) and pNF-&#x3ba;B protein expression were downregulated (0.815&#xa0;&#xb1;&#xa0;0.295 vs. 0.258&#xa0;&#xb1;&#xa0;0.130, P&#xa0;=&#xa0;0.0308). PI3K (0.365&#xa0;&#xb1;&#xa0;0.142 vs. 0.763&#xa0;&#xb1;&#xa0;0.013, P&#xa0;=&#xa0;0.0475), pAKT (0.493&#xa0;&#xb1;&#xa0;0.159 vs. 1.183&#xa0;&#xb1;&#xa0;0.344, P&#xa0;=&#xa0;0.0254) and pmTOR (0.509&#xa0;&#xb1;&#xa0;0.088 vs. 1.110&#xa0;&#xb1;&#xa0;0.190, P&#xa0;=&#xa0;0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels.<br><br>CONCLUSIONS: Vitamin K1 might ameliorate LPS-triggered skeletal muscle damage by antagonizing NF-&#x3ba;B-mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism.}, }
@article {pmid38016701, year = {2024}, author = {Lin, J and Xiong, J and Jin, Y and Wang, H and Wu, L and Chen, L and Zhang, F and Ji, G and Cui, B}, title = {Fecal microbiota transplantation through transendoscopic enteral tubing for inflammatory bowel disease: High acceptance and high satisfaction.}, journal = {Journal of gastroenterology and hepatology}, volume = {39}, number = {2}, pages = {328-336}, doi = {10.1111/jgh.16435}, pmid = {38016701}, issn = {1440-1746}, support = {BK20211384//Nature Science Foundation of Jiangsu Province/ ; }, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Inflammatory Bowel Diseases/therapy/etiology ; *Crohn Disease/therapy/etiology ; *Colitis, Ulcerative/therapy ; Personal Satisfaction ; }, abstract = {BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) has been shown to positively affect the treatment of inflammatory bowel disease (IBD). However, the safety and efficacy of FMT may depend on the route of microbiota delivery. This study investigates the acceptance, satisfaction, and selection preference of a new delivery route, transendoscopic enteral tubing (TET), for treating IBD.<br><br>METHODS: A survey was conducted among patients with IBD from five medical centers across China. The objective was to assess their acceptance, subjective feelings, and major concerns regarding two types of TET: colonic TET and mid-gut TET. In addition, the survey also analyzed the factors affecting the selection of TET and TET types among these patients.<br><br>RESULTS: The final analysis included 351 questionnaires. Up to 76.6% of patients were willing to accept TET and preferred to choose colonic TET when they first learned about TET. Patients with longer disease duration, history of enema therapy, or enteral nutrition were more open to considering TET among IBD patients. After treatment, 95.6% of patients were satisfied with TET, including colonic TET (95.9%) and mid-gut TET (95.1%). Patients with a history of enema therapy and ulcerative colitis preferred colonic TET. In contrast, those with a history of enteral nutrition and Crohn's disease were willing to choose mid-gut TET. However, some patients hesitated to accept TET due to concerns about efficacy, safety, and cost.<br><br>CONCLUSIONS: TET was highly accepted and satisfied patients with IBD. Disease type and combination therapy influenced the choice of colonic or mid-gut TET.}, }
@article {pmid38016505, year = {2024}, author = {Li, S and Chen, T and Zhou, Y and Li, X}, title = {Palmitic acid and trans-4-hydroxy-3-methoxycinnamate, the active ingredients of Yaobishu formula, reduce inflammation and pain by regulating gut microbiota and metabolic changes after lumbar disc herniation to activate autophagy and the Wnt/β-catenin pathway.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1870}, number = {2}, pages = {166972}, doi = {10.1016/j.bbadis.2023.166972}, pmid = {38016505}, issn = {1879-260X}, mesh = {Animals ; Rats ; *Intervertebral Disc Displacement ; *Gastrointestinal Microbiome ; Interleukin-18 ; Palmitic Acid ; beta Catenin ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Inflammation ; Pain ; Autophagy ; }, abstract = {The imbalance in gut microbiota triggers an inflammatory response that spreads from the gut to the discs and is associated with lumbar disc herniation (LDH). In this study, we investigated the mechanism of palmitic acid (PA) and trans-4-hydroxy-3-methoxycinnamic acid (THMC) on microbiota, metabolic homeostasis, and autophagy after LDH. The LDH rat model was established by puncturing the exposed intervertebral disc. 16S rDNA was used to assess the gut microbiome composition. The microbial metabolites were analyzed by UPLC-MS. The mechanism of PA and THMC in LDH was explored by fecal microbiota transplantation (FMT). We found that Yaobishu, PA, THMC, and the positive control drug Celebrex attenuated intervertebral disc damage in LDH rats and downregulated TRPV1, IL-1β, and IL-18 expression. In addition, Yaobishu reduced Oscillospirales and Ruminococcaceae abundances after LDH. PA increased Bacilli's abundance while decreasing Negativicutes and Ruminococcaceae abundances. Metabolomics showed that Yaobishu increased 2-hexanone, methyl isobutyl ketone, 2-methylpentan-3-one, and nonadecanoic acid levels but decreased pantetheine and urocanate levels. PA and THMC reduced uridine and urocanate levels. Yaobishu, PA, and THMC activated autophagy and the Wnt/β-catenin pathway in LDH rats. Moreover, antibiotics abrogated these effects. FMT-PA and FMT-THMC activated autophagy and decreased IL-1β, IL-18, Wnt1, β-catenin, and TRPV1 expression. FMT-PA and FMT-THMC partially reversed the effects of 3-MA. Taken together, our data suggest that Yaobishu, PA, and THMC relieve inflammation and pain by remodeling the gut microbiota and restoring metabolic homeostasis after LDH to activate autophagy and the Wnt/β-catenin pathway, which provide a new therapeutic target for LDH in the clinic.}, }
@article {pmid38016344, year = {2024}, author = {Wu, Y and Zhang, Y and Xie, B and Zhang, X and Wang, G and Yuan, S}, title = {Esketamine mitigates cognitive impairment following exposure to LPS by modulating the intestinal flora/subdiaphragmatic vagus nerve/spleen axis.}, journal = {International immunopharmacology}, volume = {126}, number = {}, pages = {111284}, doi = {10.1016/j.intimp.2023.111284}, pmid = {38016344}, issn = {1878-1705}, mesh = {Mice ; Animals ; Lipopolysaccharides/pharmacology ; Spleen ; Brain-Derived Neurotrophic Factor ; Splenomegaly ; *Gastrointestinal Microbiome ; *Coinfection ; Vagus Nerve ; Cytokines ; *Cognitive Dysfunction/drug therapy ; }, abstract = {INTRODUCTION: Susceptibility to secondary infection often increases after primary infection. Secondary infections can lead to more severe inflammatory injuries; however, the underlying mechanisms are not yet fully elucidated.<br><br>OBJECTIVE: To investigate whether esketamine treatment immediately after primary lipopolysaccharide (LPS) exposure could alleviate cognitive impairment caused by secondary infection.<br><br>METHODS: Mice were injected intraperitoneally (IP) with LPS (5&#xa0;mg/kg) 10&#xa0;days apart. Esketamine (10, 15, or 30&#xa0;mg/kg) was administered IP immediately after the primary LPS injection. Splenectomy or subdiaphragmatic vagotomy (SDV) was performed 7&#xa0;days before secondary LPS exposure or broad-spectrum antibiotic administration.<br><br>RESULTS: Splenomegaly was observed after the primary LPS injection on Days 3 and 10. Splenomegaly was attenuated by treatment with 30&#xa0;mg/kg esketamine. Esketamine treatment prevented increased plasma proinflammatory cytokines levels and cognitive dysfunction induced by secondary LPS exposure. Mice that underwent splenectomy or SDV had lower proinflammatory cytokines levels, higher hippocampal brain-derived neurotrophic factor (BDNF) levels, and improved cognitive function 1&#xa0;day after secondary infection, which was not further improved by esketamine. Fecal microbiota transplantation (FMT) from endotoxic mice treated with esketamine attenuated hippocampal BDNF downregulation and cognitive dysfunction only in pseudo germ-free (PGF) mice without splenectomy. FMT with fecal suspensions from esketamine-treated endotoxic mice abrogated splenomegaly only in PGF mice without SDV. Blocking BDNF signaling blocked esketamine's ameliorating effects on secondary LPS exposure-induced cognitive dysfunction.<br><br>CONCLUSION: The intestinal flora/subdiaphragmatic vagus nerve/spleen axis-mediated hippocampal BDNF downregulation significantly affected secondary LPS-induced systemic inflammation and cognitive dysfunction. Esketamine preserves cognitive function via this mechanism.}, }
@article {pmid38015634, year = {2023}, author = {Gurczynski, SJ and Lipinski, JH and Strauss, J and Alam, S and Huffnagle, GB and Ranjan, P and Kennedy, LH and Moore, BB and O'Dwyer, DN}, title = {Horizontal transmission of gut microbiota attenuates mortality in lung fibrosis.}, journal = {JCI insight}, volume = {9}, number = {1}, pages = {}, pmid = {38015634}, issn = {2379-3708}, support = {R00 HL139996/HL/NHLBI NIH HHS/United States ; R01 HL162659/HL/NHLBI NIH HHS/United States ; R56 HL155055/HL/NHLBI NIH HHS/United States ; }, mesh = {Mice ; Animals ; Humans ; *Gastrointestinal Microbiome/physiology ; *Pulmonary Fibrosis ; Mice, Inbred C57BL ; Lung ; *Microbiota/physiology ; }, abstract = {Pulmonary fibrosis is a chronic and often fatal disease. The pathogenesis is characterized by aberrant repair of lung parenchyma, resulting in loss of physiological homeostasis, respiratory failure, and death. The immune response in pulmonary fibrosis is dysregulated. The gut microbiome is a key regulator of immunity. The role of the gut microbiome in regulating the pulmonary immunity in lung fibrosis is poorly understood. Here, we determine the impact of gut microbiota on pulmonary fibrosis in substrains of C57BL/6 mice derived from different vendors (C57BL/6J and C57BL/6NCrl). We used germ-free models, fecal microbiota transplantation, and cohousing to transmit gut microbiota. Metagenomic studies of feces established keystone species between substrains. Pulmonary fibrosis was microbiota dependent in C57BL/6 mice. Gut microbiota were distinct by β diversity and α diversity. Mortality and lung fibrosis were attenuated in C57BL/6NCrl mice. Elevated CD4+IL-10+ T cells and lower IL-6 occurred in C57BL/6NCrl mice. Horizontal transmission of microbiota by cohousing attenuated mortality in C57BL/6J mice and promoted a transcriptionally altered pulmonary immunity. Temporal changes in lung and gut microbiota demonstrated that gut microbiota contributed largely to immunological phenotype. Key regulatory gut microbiota contributed to lung fibrosis, generating rationale for human studies.}, }
@article {pmid38015106, year = {2023}, author = {Sun, L and Li, Z and Hu, C and Ding, J and Zhou, Q and Pang, G and Wu, Z and Yang, R and Li, S and Li, J and Cai, J and Sun, Y and Li, R and Zhen, H and Sun, S and Zhang, J and Fang, M and Chen, Z and Lv, Y and Cao, Q and Sun, Y and Gong, R and Huang, Z and Duan, Y and Liu, H and Dong, J and Li, J and Ruan, J and Lu, H and He, B and Li, N and Li, T and Xue, W and Li, Y and Shen, J and Yang, F and Zhao, C and Liang, Q and Zhang, M and Chen, C and Gong, H and Hou, Y and Wang, J and Zhang, Y and Yang, H and Zhu, S and Xiao, L and Jin, Z and Guo, H and Zhao, P and Brix, S and Xu, X and Jia, H and Kristiansen, K and Yang, Z and Nie, C}, title = {Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging.}, journal = {Aging cell}, volume = {22}, number = {12}, pages = {e14028}, pmid = {38015106}, issn = {1474-9726}, support = {U23A20470//National Scientific Foundation of P. R. China/ ; 82260289//National Scientific Foundation of P. R. China/ ; 91849132//National Scientific Foundation of P. R. China/ ; 81571385//National Scientific Foundation of P. R. China/ ; BJ-2018-139//Beijing Hospital Nova Project/ ; 2021-I2M-1-050//CAMS Innovation Fund for Medical Sciences/ ; 2021YFE0111800//National Key Research and Development Program of China/ ; 2023YFC3603300//National Key Research and Development Program of China/ ; 2018YFC2000400//National Key Research and Development Program of China/ ; 202001AY070001-011//The Priority Union Foundation of Yunnan Provincial Science and Technology Department/ ; BJ-2023-168//National High Level Hospital Clinical Research Funding/ ; BJ-2023-075//National High Level Hospital Clinical Research Funding/ ; 2022ZD0211600//Science and Technology lnnovation 2030 Major Projects/ ; }, mesh = {Humans ; Aged ; *Gastrointestinal Microbiome ; China ; Metabolome ; Aging ; Biomarkers ; Kidney ; }, abstract = {Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.}, }
@article {pmid38014241, year = {2023}, author = {Frith, ME and Kashyap, PC and Linden, DR and Theriault, B and Chang, EB}, title = {Microbiota-dependent early life programming of gastrointestinal motility.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.11.08.566304}, pmid = {38014241}, issn = {2692-8205}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DK129315/DK/NIDDK NIH HHS/United States ; }, abstract = {Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNAseq of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later - or not at all - showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early life microbiome in later life dysmotility.}, }
@article {pmid38012646, year = {2023}, author = {Kim, N and Ju, IG and Jeon, SH and Lee, Y and Jung, MJ and Gee, MS and Cho, JS and Inn, KS and Garrett-Sinha, LA and Oh, MS and Lee, JK}, title = {Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer's disease mouse model.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {282}, pmid = {38012646}, issn = {1742-2094}, support = {NRF-2022R1A6A3A01087341//National Research Foundation of Korea/ ; NRF-2017R1A5A2014768//National Research Foundation of Korea/ ; }, mesh = {Mice ; Animals ; *Alzheimer Disease/pathology ; Microglia/metabolism ; M Cells ; Neuroinflammatory Diseases ; Amyloid beta-Peptides/metabolism ; Memory Disorders ; Mice, Knockout ; Phenotype ; Disease Models, Animal ; Mice, Transgenic ; }, abstract = {BACKGROUND: The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer's disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown.<br><br>METHODS: Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) na&#xef;ve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age.<br><br>RESULTS: In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-&#x3b2; accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib[-/-] mice.<br><br>CONCLUSION: Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications.}, }
@article {pmid38012463, year = {2023}, author = {Hart, NH and Wallen, MP and Farley, MJ and Haywood, D and Boytar, AN and Secombe, K and Joseph, R and Chan, RJ and Kenkhuis, MF and Buffart, LM and Skinner, TL and Wardill, HR}, title = {Exercise and the gut microbiome: implications for supportive care in cancer.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {31}, number = {12}, pages = {724}, pmid = {38012463}, issn = {1433-7339}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Exercise/physiology ; *Neoplasms/therapy ; Diet ; *Sports ; *Probiotics/therapeutic use ; }, abstract = {PURPOSE: Growing recognition of the gut microbiome as an influential modulator of cancer treatment efficacy and toxicity has led to the emergence of clinical interventions targeting the microbiome to enhance cancer and health outcomes. The highly modifiable nature of microbiota to endogenous, exogenous, and environmental inputs enables interventions to promote resilience of the gut microbiome that have rapid effects on host health, or response to cancer treatment. While diet, probiotics, and faecal microbiota transplant are primary avenues of therapy focused on restoring or protecting gut function in people undergoing cancer treatment, the role of physical activity and exercise has scarcely been examined in this population.<br><br>METHODS: A narrative review was conducted to explore the nexus between cancer care and the gut microbiome in the context of physical activity and exercise as a widely available and clinically effective supportive care strategy used by cancer survivors.<br><br>RESULTS: Exercise can facilitate a more diverse gut microbiome and functional metabolome in humans; however, most physical activity and exercise studies have been conducted in healthy or athletic populations, primarily using aerobic exercise modalities. A scarcity of exercise and microbiome studies in cancer exists.<br><br>CONCLUSIONS: Exercise remains an attractive avenue to promote microbiome health in cancer survivors. Future research should elucidate the various influences of exercise modalities, intensities, frequencies, durations, and volumes to explore dose-response relationships between exercise and the gut microbiome among cancer survivors, as well as multifaceted approaches (such as diet and probiotics), and examine the influences of exercise on the gut microbiome and associated symptom burden prior to, during, and following cancer treatment.}, }
@article {pmid38011635, year = {2023}, author = {Choueiry, F and Gold, A and Xu, R and Zhang, S and Zhu, J}, title = {Secondary-Electrospray Ionization Mass Spectrometry-Based Online Analyses of Mouse Volatilome Uncover Gut Microbiome-Dictated Metabolic Changes in the Host.}, journal = {Journal of the American Society for Mass Spectrometry}, volume = {34}, number = {12}, pages = {2793-2800}, doi = {10.1021/jasms.3c00304}, pmid = {38011635}, issn = {1879-1123}, mesh = {Humans ; Animals ; Mice ; Spectrometry, Mass, Electrospray Ionization/methods ; *Gastrointestinal Microbiome ; *Volatile Organic Compounds/analysis ; Metabolome ; Bacteria/chemistry ; Mammals ; }, abstract = {The symbiotic relationship between the gut microbial population is capable of regulating numerous aspects of host physiology, including metabolism. Bacteria can modulate the metabolic processes of the host by feeding on nutritional components within the lumen and releasing bioactive components into circulation. Endogenous volatile organic compound (VOC) synthesis is dependent on the availability of precursors found in mammalian metabolism. Herein, we report that microbial-mediated metabolic influences can alter the host volatilome and the prominent volatile changes can be uncovered by a novel volatile analysis technique named secondary electrospray ionization mass spectrometry. Mice were subjected to an antibiotic cocktail to deplete the microbiome and then inoculated with either single strain bacteria or fecal matter transplantation (FMT) to replete the microbial population in the gut. VOC sampling was achieved by using an advanced secondary electrospray ionization (SESI) source that directly mounted onto a Thermo Q-Exactive high-resolution mass spectrometer (HRMS). A principal component analysis summarizing the volatile profiles of the mice revealed independent clustering of each strain of the FMT-inoculated groups, suggesting unique volatile profiles. The Mummichog algorithm uncovered phenylalanine metabolism as a significantly altered metabolic profile in the volatilome of the microbiome-repleted mice. Our results indicated that the systemic metabolic changes incurred by the host are translated to unique volatile profiles correlated to the diversity of the microbial population colonized within the host. It is thus possible to take advantage of SESI-HRMS-based platforms for noninvasive screening of VOCs to determine the contribution of various microbial colonization within human gut that may impact host health.}, }
@article {pmid38010914, year = {2023}, author = {Liang, D and Liu, H and Jin, R and Feng, R and Wang, J and Qin, C and Zhang, R and Chen, Y and Zhang, J and Teng, J and Tang, B and Ding, X and Wang, X}, title = {Escherichia coli triggers α-synuclein pathology in the LRRK2 transgenic mouse model of PD.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2276296}, pmid = {38010914}, issn = {1949-0984}, mesh = {Mice ; Animals ; *Parkinson Disease/genetics/pathology ; Mice, Transgenic ; alpha-Synuclein/genetics/metabolism ; Escherichia coli/genetics/metabolism ; *Gastrointestinal Microbiome ; }, abstract = {Alpha-synuclein (α-syn) pathology is the hallmark of Parkinson's disease (PD). The leucine-rich repeat kinase 2 (LRRK2) gene is a major-effect risk gene for sporadic PD (sPD). However, what environmental factors may trigger the formation of α-syn pathology in carriers of LRRK2 risk variants are still unknown. Here, we report that a markedly increased abundance of Escherichia coli (E. coli) in the intestinal microbiota was detected in LRRK2 risk variant(R1628P or G2385R) carriers with sPD compared with carriers without sPD. Animal experiments showed that E. coli administration triggered pathological α-syn accumulation in the colon and spread to the brain via the gut-brain axis in Lrrk2 R1628P mice, due to the co-occurrence of Lrrk2 variant-induced inhibition of α-syn autophagic degradation and increased phosphorylation of α-syn caused by curli in E. coli-derived extracellular vesicles. Fecal microbiota transplantation (FMT) effectively ameliorated motor deficits and α-syn pathology in Lrrk2 R1628P mice. Our findings elaborate on the mechanism that E. coli triggers α-syn pathology in Lrrk2 R1628P mice, and highlight a novel gene-environment interaction pattern in LRRK2 risk variants. Even more importantly, the findings reveal the interplay between the specific risk gene and the matched environmental factors triggers the initiation of α-syn pathology in sPD.}, }
@article {pmid38010886, year = {2023}, author = {Garrett, S and Asada, MC and Sun, J}, title = {Axin1's mystique in manipulating microbiome amidst colitis.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2286674}, pmid = {38010886}, issn = {1949-0984}, support = {I01 BX004824/BX/BLRD VA/United States ; R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; R01 DK134343/DK/NIDDK NIH HHS/United States ; }, mesh = {Inflammation ; Akkermansia ; Paneth Cells ; *Axin Protein/genetics ; Mice ; Animals ; *Gastrointestinal Microbiome ; beta Catenin ; *Colitis/chemically induced/genetics ; *Microbiota ; }, abstract = {Classically, Axin1 is considered a regulator of Wnt/β-catenin signaling. However, Axin1's roles in host-microbial interactions have been unknown. Our recent study has demonstrated that deletion of intestinal epithelial Axin1 in epithelial cells and Paneth cells protects the host against colitis by enhancing Akkermansia muciniphila. Loss of intestinal epithelial or Paneth cell Axin1 results in increased Wnt/β-catenin signaling, proliferation, and cell migration. This is associated with morphologically altered goblet and Paneth cells, including increased Muc2 and decreased lysozyme. Axin1 deletion specifically enriched Akkermansia muciniphila. Akkermansia muciniphila in Axin1 knockout mice is the driver of protection against DSS-induced inflammation. Here, we feature several significant conceptual changes, such as differences between Axin1 and Axin2, Axin1 in innate immunity and microbial homeostasis, and Axin1 reduction of Akkermansia muciniphila. We discuss an important trend in the field related to Paneth cells and tissue-specific Axin1 manipulation of microbiome in health and inflammation.}, }
@article {pmid38010872, year = {2023}, author = {Ahmad, R and Kumar, B and Thapa, I and Talmon, GA and Salomon, J and Ramer-Tait, AE and Bastola, DK and Dhawan, P and Singh, AB}, title = {Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2282789}, pmid = {38010872}, issn = {1949-0984}, support = {R01 DK124095/DK/NIDDK NIH HHS/United States ; P30 GM110768/GM/NIGMS NIH HHS/United States ; R01 CA250383/CA/NCI NIH HHS/United States ; I01 BX002086/BX/BLRD VA/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; I01 BX002761/BX/BLRD VA/United States ; P20 GM103427/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Claudin-3/genetics ; *Colitis/genetics/complications ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/complications ; Animals ; Mice ; }, abstract = {Dysregulation of both the gut barrier and microbiota (dysbiosis) promotes susceptibility to and severity of Inflammatory Bowel Diseases (IBD). Leaky gut and dysbiosis often coexist; however, potential interdependence and molecular regulation are not well understood. Robust expression of claudin-3 (CLDN3) characterizes the gut epithelium, and studies have demonstrated a positive association between CLDN3 expression and gut barrier maturity and integrity, including in response to probiotics. However, the exact status and causal role of CLDN3 in IBD and regulation of gut dysbiosis remain unknown. Analysis of mouse and human IBD cohorts helped examine CLDN3 expression in IBD. The causal role was determined by modeling CLDN3 loss of expression during experimental colitis. 16S sequencing and in silico analysis helped examine gut microbiota diversity between Cldn3KO and WT mice and potential host metabolic responses. Fecal microbiota transplant (FMT) studies were performed to assess the role of gut dysbiosis in the increased susceptibility of Cldn3KO mice to colitis. A significant decrease in CLDN3 expression characterized IBD and CLDN3 loss of expression promoted colitis. 16S sequencing analysis suggested gut microbiota changes in Cldn3KO mice that were capable of modulating fatty acid metabolism and oxidative stress response. FMT from naïve Cldn3KO mice promoted colitis susceptibility in recipient germ-free mice (GFM) compared with GFM-receiving microbiota from WT mice. Our data demonstrate a critical role of CLDN3 in maintaining normal gut microbiota and inflammatory responses, which can be harnessed to develop novel therapeutic opportunities for patients with IBD.}, }
@article {pmid38010168, year = {2023}, author = {Ye, H and Ghosh, TS and Hueston, CM and Vlckova, K and Golubeva, AV and Hyland, NP and O'Toole, PW}, title = {Engraftment of aging-related human gut microbiota and the effect of a seven-species consortium in a pre-clinical model.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2282796}, pmid = {38010168}, issn = {1949-0984}, mesh = {Humans ; Animals ; Mice ; Aged ; *Gastrointestinal Microbiome/genetics ; *Frailty ; Bacteroidetes ; Feces/microbiology ; Fecal Microbiota Transplantation ; Acetates ; }, abstract = {Human aging is characterized by gut microbiome alteration and differential loss of gut commensal species associated with the onset of frailty. The administration of cultured commensal strains to replenish lost taxa could potentially promote healthy aging. To investigate the interaction of whole microbiomes and administered strains, we transplanted gut microbiota from a frail or healthy elderly subject into germ-free mice. We supplemented the frail-donor recipient group with a defined consortium of taxa (the "S7") that we identified by analyzing healthy aging subjects in our previous studies and whose abundance correlated with health-promoting dietary intervention. Inoculation with a frail or a healthy donor microbiome resulted in differential microbiota compositions in murine recipients 5 weeks post-transplantation. Fecal acetate levels were significantly higher in healthy donor recipient mice than in frail donor recipient mice after 4 weeks. However, the frailty-related phenotype was not replicated in recipient mice with single-dose microbiota transplantation from a healthy and a frail donor. Five S7 species colonized successfully in germ-free mice, with a relatively high abundance of Barnesiella intestinihominis and Eubacterium rectale. The engraftment of five S7 species in germ-free mice increased fecal acetate levels and reduced colon permeability and plasma TNF-ɑ concentration. Supplementation with the S7 in frail-microbiota recipient mice did not increase alpha-diversity but significantly increased the abundance of Barnesiella intestinihominis. S7 supplementation showed the potential for improving spatial reference memory in frail-microbiota recipient mice. Collectively, these data highlight the challenge of elderly microbiota engraftment in the germ-free mouse model but show promise for modulating the gut microbiome of frail elderly subjects by administering an artificial gut microbe consortium associated with healthy aging.}, }
@article {pmid38009301, year = {2024}, author = {Xiong, Y and He, Y and Chen, Z and Wu, T and Xiong, Y and Peng, Y and Yang, X and Liu, Y and Zhou, J and Zhou, H and Zhang, W and Shu, Y and Li, X and Li, Q}, title = {Lactobacillus induced by irbesartan on spontaneously hypertensive rat contribute to its antihypertensive effect.}, journal = {Journal of hypertension}, volume = {42}, number = {3}, pages = {460-470}, doi = {10.1097/HJH.0000000000003613}, pmid = {38009301}, issn = {1473-5598}, mesh = {Rats ; Animals ; *Antihypertensive Agents/pharmacology/therapeutic use ; Irbesartan/therapeutic use ; Rats, Inbred SHR ; Lactobacillus/genetics ; Chromatography, Liquid ; Dysbiosis ; RNA, Ribosomal, 16S ; Rats, Inbred WKY ; Tandem Mass Spectrometry ; *Hypertension ; Blood Pressure ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; }, abstract = {OBJECTIVE: Hypertension is linked to gut dysbiosis. Here, the impact of the angiotensin receptor antagonist irbesartan on the gut microbiota of spontaneously hypertensive rats (SHR) were investigated. In addition, we assessed their contribution to its antihypertensive effect.<br><br>METHODS: Eight-week-old Wistar-Kyoto (WKY) rats and SHR were administered irbesartan for 8 weeks. Fecal microbiota transplantation (FMT) was performed from SHR treated with irbesartan or untreated SHR to recipient untreated SHR. The preventive effect of Lactobacillus on hypertension in SHR was evaluated. Blood pressure (BP) was calculated using a tail-sleeve sphygmomanometer. To better assess the composition of the gut microbiota, the V3-V4 region of the 16S rRNA gene was amplified while short-chain fatty acids (SCFAs) in feces were tested by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).<br><br>RESULTS: Irbesartan restored gut dysbiosis, increased the abundance of Lactobacillus , and improved anti-inflammatory ability, antioxidative ability, intestinal integrity, and intestinal inflammation in SHR. The microbiota in SHR-treated irbesartan could reduce BP and improve antioxidative ability and gut integrity in SHR. Lactobacillus johnsonii (L. johnsonii) and Lactobacillus reuteri (L. reuteri) reduced BP, restored gut dysbiosis and improved anti-inflammatory ability, antioxidative ability, intestinal integrity in SHR. Most notably, irbesartan, L. johnsonii , and L. reuteri can significantly increase SCFA content in SHR feces.<br><br>CONCLUSION: The current study demonstrated that irbesartan treatment ameliorated gut dysbiosis in SHR. Irbesartan induced alterations in gut microbiota, with increased prevalence of Lactobacillus .}, }
@article {pmid38009195, year = {2024}, author = {Hu, S and Zhou, J and Hao, J and Zhong, Z and Wu, H and Zhang, P and Yang, J and Guo, H and Chi, J}, title = {Emodin ameliorates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis through the remodeling of gut microbiota composition.}, journal = {American journal of physiology. Cell physiology}, volume = {326}, number = {1}, pages = {C161-C176}, doi = {10.1152/ajpcell.00477.2023}, pmid = {38009195}, issn = {1522-1563}, support = {No. 82174204//MOST | National Natural Science Foundation of China (NSFC)/ ; No. 81873120//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Animals ; Mice ; *Emodin/pharmacology ; *Gastrointestinal Microbiome ; Cardiotoxicity ; *Ferroptosis ; NF-E2-Related Factor 2/genetics ; Doxorubicin/toxicity ; Myocytes, Cardiac ; }, abstract = {The relationship between gut microbiota and doxorubicin-induced cardiotoxicity (DIC) is becoming increasingly clear. Emodin (EMO), a naturally occurring anthraquinone, exerts cardioprotective effects and plays a protective role by regulating gut microbiota composition. Therefore, the protective effect of EMO against DIC injury and its underlying mechanisms are worth investigating. In this study, we analyzed the differences in the gut microbiota in recipient mice transplanted with different flora using 16S-rDNA sequencing, analyzed the differences in serum metabolites among groups of mice using a nontargeted gas chromatography-mass spectrometry coupling system, and assessed cardiac function based on cardiac morphological staining, cardiac injury markers, and ferroptosis indicator assays. We found EMO ameliorated DIC and ferroptosis, as evidenced by decreased myocardial fibrosis, cardiomyocyte hypertrophy, and myocardial disorganization; improved ferroptosis indicators; and the maintenance of normal mitochondrial morphology. The protective effect of EMO was eliminated by the scavenging effect of antibiotics on the gut microbiota. Through fecal microbiota transplantation (FMT), we found that EMO restored the gut microbiota disrupted by doxorubicin (DOX) to near-normal levels. This was evidenced by an increased proportion of Bacteroidota and a decreased proportion of Verrucomicrobiota. FMT resulted in changes in the composition of serum metabolites. Mice transplanted with EMO-improved gut microbiota showed better cardiac function and ferroptosis indices; however, these beneficial effects were not observed in Nrf2 (Nfe2l2)[-/-] mice. Overall, EMO exerted a protective effect against DIC by attenuating ferroptosis, and the above effects occurred by remodeling the composition of gut microbiota perturbed by DOX and required Nrf2 mediation.NEW &amp; NOTEWORTHY This study demonstrated for the first time the protective effect of emodin against DIC and verified by FMT that its cardioprotective effect was achieved by remodeling gut microbiota composition, resulting in attenuation of ferroptosis. Furthermore, we demonstrated that these effects were mediated by the redox-related gene Nrf2.}, }
@article {pmid38007451, year = {2023}, author = {Ma, J and Zhou, M and Song, Z and Deng, Y and Xia, S and Li, Y and Huang, X and Xiao, D and Yin, Y and Yin, J}, title = {Clec7a drives gut fungus-mediated host lipid deposition.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {264}, pmid = {38007451}, issn = {2049-2618}, support = {2022YFD1301500//National Key Research and Development Program of China/ ; 32172761//National Natural Science Foundation of China/ ; CARS-37//Earmarked Fund for China Agriculture Research System/ ; }, mesh = {Animals ; Humans ; Mice ; *Antifungal Agents ; Diet, High-Fat/adverse effects ; Fungi ; Lipids ; Mice, Inbred C57BL ; *Obesity/metabolism ; Swine ; }, abstract = {BACKGROUND: Compared to that of bacteria, the role of gut fungi in obesity development remains unknown.<br><br>RESULTS: Here, alterations in gut fungal biodiversity and composition were confirmed in obese pig models and high-fat diet (HFD)-fed mice. Antifungal drugs improved diet-induced obesity, while fungal reconstruction by cohousing or fecal microbiota transplantation maintained the obese phenotype in HFD-fed mice. Fungal profiling identified 5 fungal species associated with obesity. Specifically, Ascomycota_sp. and Microascaceae_sp. were reduced in obese mice and negatively correlated with fat content. Oral supplementation with fungi was sufficient to prevent and treat diet-induced obesity. Clec7a, which is involved in fungal recognition, was highly expressed in HFD-fed mice. The Clec7a agonist accelerated diet-induced obesity, while Clec7a deficieny in mice resulted in resistance to diet-induced obesity and blocked the anti-obese effect of antifungal drugs and fungi.<br><br>CONCLUSIONS: Taken together, these results indicate that gut fungi/Clec7a signaling is involved in diet-induced obesity and may have therapeutic implications as a biomarker for metabolic dysregulation in humans. Video Abstract.}, }
@article {pmid38004817, year = {2023}, author = {Parigi, TL and Vieujean, S and Paridaens, K and Dalgaard, K and Peyrin-Biroulet, L and Danese, S}, title = {Efficacy, Safety, and Concerns on Microbiota Modulation, Antibiotics, Probiotics, and Fecal Microbial Transplant for Inflammatory Bowel Disease and Other Gastrointestinal Conditions: Results from an International Survey.}, journal = {Microorganisms}, volume = {11}, number = {11}, pages = {}, pmid = {38004817}, issn = {2076-2607}, abstract = {The gut microbiota play a pivotal role in human health. Dysbiosis, alterations in microbiota composition and function, is associated with gastrointestinal disorders, including inflammatory bowel disease (IBD). This international survey aimed to assess physicians' experiences, perceptions, and practices related to microbiome modulation for gastrointestinal conditions, with a focus on IBD. Results from 142 healthcare professionals, predominantly gastroenterologists, confirmed a consensus on the relevance of the gut microbiota in IBD pathogenesis. However, the utilization of microbial composition analysis and probiotics in clinical practice was limited, primarily due to the lack of standardized guidelines and supporting evidence. Physicians held conflicting views on antibiotics, recognizing their potential for inducing remission but also causing flares in IBD. Respondents also had varying opinions on the efficacy of fecal microbiota transplantation (FMT) for different gastrointestinal conditions, with higher confidence in FMT effectiveness for irritable bowel syndrome with diarrhea, pouchitis, and ulcerative colitis. Concerns on FMT included uncertainty about effect duration, administration intervals, and conflicting evidence. Donor selection was believed to be a crucial factor in FMT outcomes. This survey highlights the need for further research and evidence-based guidelines to optimize the use of microbiome-based therapies in clinical practice. As our understanding of the gut microbiome continues to evolve, these insights will contribute to more informed and personalized approaches to managing gastrointestinal disorders.}, }
@article {pmid38004765, year = {2023}, author = {Salandre, A and Delannoy, J and Goudiaby, MTB and Barbut, F and Thomas, M and Waligora-Dupriet, AJ and Kapel, N}, title = {A Simple In Vitro Test to Select Stools for Fecal Microbiota Transplantation to Limit Intestinal Carriage of Extensively Drug-Resistant Bacteria.}, journal = {Microorganisms}, volume = {11}, number = {11}, pages = {}, pmid = {38004765}, issn = {2076-2607}, abstract = {Treatment options for multidrug-resistant bacterial infections are limited and often ineffective. Fecal microbiota transplantation (FMT) has emerged as a promising therapy for intestinal multidrug-resistant bacterial decolonization. However, clinical results are discrepant. The aim of our pilot study was to evaluate the screening performance of a simple diagnostic tool to select fecal samples that will be effective in decolonizing the intestine. Fecal samples from 10 healthy subjects were selected. We developed an agar spot test to evaluate their antagonistic activity toward the growth of VanA Enterococcus faecium and OXA-48-producing Klebsiella pneumoniae, two of the most serious and urgent threats of antibiotic resistance. Most fecal samples were able to limit the growth of both bacteria in vitro but with large inter-individual variation. The samples with the highest and lowest antagonistic activity were used for FMT in a mouse model of intestinal colonization. FMT was not successful in reducing intestinal colonization with VanA Enterococcus faecium, whereas FMT performed with the fecal sample showing the highest activity on the agar spot test was able to significantly reduce the intestinal colonization of mice with Klebsiella pneumoniae OXA-48. The agar spot test could thus serve as a reliable screening tool to select stool samples with the best potential to eradicate/reduce multidrug-resistant bacteria carriage after FMT.}, }
@article {pmid38004758, year = {2023}, author = {Yan, P and Luo, S and Guo, L and Wang, X and Ren, X and Lv, J and Chen, Y and Lin, X and Chen, J and Wang, R}, title = {Unraveling Intestinal Microbial Shifts in ESRD and Kidney Transplantation: Implications for Disease-Related Dysbiosis.}, journal = {Microorganisms}, volume = {11}, number = {11}, pages = {}, pmid = {38004758}, issn = {2076-2607}, support = {82070766//National Natural Science Foundation of China/ ; 2022RC147//Medical Health Science and Technology Project of Zhejiang Provincial Health Commission/ ; LQ23H050003//Zhejiang Provincial Natural Science Foundation of China/ ; }, abstract = {The composition of the gut microbiome is profoundly influenced by the accumulation of toxins in end-stage renal disease (ESRD) and specific medical treatments during kidney transplantation (KT). However, variations in results may arise due to factors such as genetics, dietary habits, and the strategy of anti-rejection therapy. Therefore, we conducted a 16S rRNA sequencing study to characterize intestinal microbiomes by using 75 fecal specimens obtained from 25 paired Chinese living donors (LDs) of kidneys and recipients before and after KT. Surprisingly, similar enterotypes were observed between healthy LDs and ESRD recipients. Nonetheless, following KT, the fecal communities of recipients exhibited distinct clustering, which was primarily characterized by Escherichia-Shigella and Streptococcus at the genus level, along with a reduction in the diversity of microbiota. To further explore the characteristics of gut microorganisms in early rejection episodes, two recipients with biopsy-proven borderline changes during follow-up were enrolled in a preliminary sub-cohort study. Our findings reveal a comparable construction of gut microbiota between ESRD patients and their healthy relatives while also highlighting the significant impact of KT on gut microbial composition.}, }
@article {pmid38004180, year = {2023}, author = {Zhou, J and Ho, V}, title = {Role of Baseline Gut Microbiota on Response to Fiber Intervention in Individuals with Irritable Bowel Syndrome.}, journal = {Nutrients}, volume = {15}, number = {22}, pages = {}, pmid = {38004180}, issn = {2072-6643}, support = {Investigator Initiated Funding Scheme//Nestl&#xe9; Foundation/ ; }, mesh = {Humans ; *Irritable Bowel Syndrome/therapy ; *Gastrointestinal Microbiome/physiology ; Feces ; *Microbiota ; Fecal Microbiota Transplantation ; }, abstract = {Irritable bowel syndrome (IBS) is one of the most prevalent functional gut disorders in the world. Partially hydrolyzed guar gum, a low-viscosity soluble fiber, has shown promise in the management of IBS-related symptoms. In this study, we aimed to determine if an individual's baseline gut microbiota impacted their response to a partially hydrolyzed guar gum intervention. Patients diagnosed with IBS undertook a 90-day intervention and follow-up. IBS symptom severity, tolerability, quality-of-life, and fecal microbiome composition were recorded during this study. Patients with normal microbiota diversity (Shannon index ≥ 3) showed significant improvements to IBS symptom scores, quality-of-life, and better tolerated the intervention compared to patients with low microbiota diversity (Shannon index < 3). Our findings suggest that an individual's baseline microbiome composition exerts a substantial influence on their response to fiber intervention. Future investigations should explore a symbiotic approach to the treatment of IBS.}, }
@article {pmid38004128, year = {2023}, author = {He, S and Lin, F and Hu, X and Pan, P}, title = {Gut Microbiome-Based Therapeutics in Critically Ill Adult Patients-A Narrative Review.}, journal = {Nutrients}, volume = {15}, number = {22}, pages = {}, pmid = {38004128}, issn = {2072-6643}, support = {z047-02//The national key clinical specialist construction programs of China/ ; }, mesh = {Humans ; Adult ; *Gastrointestinal Microbiome/physiology ; Critical Illness/therapy ; *Microbiota/physiology ; Fecal Microbiota Transplantation/adverse effects ; Prognosis ; Dysbiosis/therapy/etiology ; }, abstract = {The gut microbiota plays a crucial role in the human microenvironment. Dysbiosis of the gut microbiota is a common pathophysiological phenomenon in critically ill patients. Therefore, utilizing intestinal microbiota to prevent complications and improve the prognosis of critically ill patients is a possible therapeutic direction. The gut microbiome-based therapeutics approach focuses on improving intestinal microbiota homeostasis by modulating its diversity, or treating critical illness by altering the metabolites of intestinal microbiota. There is growing evidence that fecal microbiota transplantation (FMT), selective digestive decontamination (SDD), and microbiota-derived therapies are all effective treatments for critical illness. However, different treatments are appropriate for different conditions, and more evidence is needed to support the selection of optimal gut microbiota-related treatments for different diseases. This narrative review summarizes the curative effects and limitations of microbiome-based therapeutics in different critically ill adult patients, aiming to provide possible directions for gut microbiome-based therapeutics for critically ill patients such as ventilator-associated pneumonia, sepsis, acute respiratory distress syndrome, and COVID-19, etc.}, }
@article {pmid38002138, year = {2023}, author = {Xiao, N and Ruan, S and Mo, Q and Zhao, M and Feng, F}, title = {The Effect of Sodium Benzoate on Host Health: Insight into Physiological Indexes and Gut Microbiota.}, journal = {Foods (Basel, Switzerland)}, volume = {12}, number = {22}, pages = {}, pmid = {38002138}, issn = {2304-8158}, support = {32072224,32001693 and 32172214//National Natural Science Foundation of China/ ; LD19C200001and LQ21C200007//Zhejiang Provincial Natural Science Foundation/ ; }, abstract = {Sodium benzoate (SB) is a common food preservative widely used in the food industry. However, the effects of SB intake on host health at different stages were still unclear. Hence, we investigated the impact of SB with three concentrations (150 mg/kg, 500 mg/kg and 1000 mg/kg) and at three stages (intake for 5-weeks, intake for 10-weeks and removal for 5 weeks) on host health in normal mice. The results showed that SB intake for 5 weeks slightly changed gut microbiota composition, but it significantly increased TG (only 150 mg/kg and 1000 mg/kg) and blood glucose levels (only 500 mg/kg) and promoted the secretion of interleukin (IL)-1β and IL-6 (p < 0.01). However, SB intake for 10 weeks mostly maintained normal glucolipid metabolism; although, IL-1β (p < 0.01) and IL-6 (p < 0.05) levels were also significantly increased and positively regulated the gut microbiota by significantly increasing the relative abundance of Lactobacillus and significantly decreasing the relative abundance of Ileibacterium. Meanwhile, the safety of SB for host metabolism and gut microbiota was also confirmed via a fecal microbiota transplantation experiment. In addition, we found that SB removal after 10 weeks of intake significantly increased the levels of blood glucose, insulin and HOMA-IR index, which might be attributed to gut microbiota dysbiosis. Mechanistically, these positive effects and negative effects had no close relationship with the concentration of short-chain fatty acids in the gut, which might be associated with metabolites of SB or special bacterial strains. In short, this work provided positive evidence for the safety of SB consumption within the recommended range.}, }
@article {pmid38001930, year = {2023}, author = {Boicean, A and Birlutiu, V and Ichim, C and Brusnic, O and Onișor, DM}, title = {Fecal Microbiota Transplantation in Liver Cirrhosis.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, pmid = {38001930}, issn = {2227-9059}, abstract = {The human gastrointestinal tract houses a diverse array of probiotic and pathogenic bacteria and any alterations in this microbial composition can exert a significant influence on an individual's well-being. It is well-established that imbalances in the gut microbiota play a pivotal role in the development of liver diseases. In light of this, a new adjuvant therapy for liver diseases could be regulating the intestinal microbiota. Through fecal microbiota transplantation, patients whose microbiomes are compromised are treated with stool from healthy donors in an attempt to restore a normal microbiome and alleviate their symptoms. A review of cross-sectional studies and case reports suggests that fecal microbiota transplants may offer effective treatment for chronic liver diseases. Adding to the potential of this emerging therapy, recent research has indicated that fecal microbiota transplantation holds promise as a therapeutic approach specifically for liver cirrhosis. By introducing a diverse range of beneficial microorganisms into the gut, this innovative treatment aims to address the microbial imbalances often observed in cirrhotic patients. While further validation is still required, these preliminary findings highlight the potential impact of fecal microbiota transplantation as a novel and targeted method for managing liver cirrhosis. We aimed to summarize the current state of understanding regarding this procedure, as a new therapeutic method for liver cirrhosis, as well as to explain its clinical application and future potential.}, }
@article {pmid38001551, year = {2023}, author = {Xu, H and Fang, F and Wu, K and Song, J and Li, Y and Lu, X and Liu, J and Zhou, L and Yu, W and Yu, F and Gao, J}, title = {Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {262}, pmid = {38001551}, issn = {2049-2618}, support = {32001696//National Natural Science Foundation of China/ ; 2021AC19445//Specific Research Project of Guangxi for Research Bases and Talents/ ; }, mesh = {Animals ; Mice ; *Bile Acids and Salts/metabolism ; Diet, High-Fat ; *Gastrointestinal Microbiome/physiology ; Lipid Metabolism ; Liver/metabolism ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Diet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the humanized dyslipidemia mice model was successfully built by using fecal microbiota transplantation from dyslipidemic donors (FMT-dd) to study the causal role of gut microbiota in diet-induced dyslipidemia.<br><br>RESULTS: We demonstrated that FMT-dd reshaped the gut microbiota of mice by increasing Faecalibaculum and Ruminococcaceae UCG-010, which then elevated serum cholicacid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA), reduced bile acid synthesis and increased cholesterol accumulation via the hepatic farnesoid X receptor-small heterodimer partner (FXR-SHP) axis. Nevertheless, high-fat diet led to decreased Muribaculum in the humanized dyslipidemia mice induced by FMT-dd, which resulted in reduced intestinal hyodeoxycholic acid (HDCA), raised bile acid synthesis and increased lipid absorption via the intestinal farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) axis.<br><br>CONCLUSIONS: Our studies implicated that intestinal FXR is responsible for the regulation of lipid metabolism in diet-induced dyslipidemia mediated by gut microbiota-bile acid crosstalk. Video Abstract.}, }
@article {pmid38001323, year = {2024}, author = {Yang, Y and Yan, J and Li, S and Liu, M and Han, R and Wang, Y and Wang, Z and Wang, D}, title = {Efficacy of fecal microbiota transplantation in type 2 diabetes mellitus: a systematic review and meta-analysis.}, journal = {Endocrine}, volume = {84}, number = {1}, pages = {48-62}, pmid = {38001323}, issn = {1559-0100}, support = {(No.[2020] No.23)//Project Fund of Clinical Medicine Excellent Talents funded by Hebei Provincial Department of Finance (No.: [2020] No.23);/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Diabetes Mellitus, Type 2/drug therapy ; Triglycerides ; Cholesterol ; Body Mass Index ; Lipoproteins, HDL ; Blood Glucose/metabolism ; }, abstract = {OBJECTIVE: Type 2 diabetes mellitus (T2DM) is one of the common metabolic diseases worldwide, and studies have found significant differences in the composition and ratio of intestinal flora between patients with T2DM and normal glucose tolerance, and fecal microbiota transplantation (FMT) may modulate the composition of the intestinal microbiota thereby alleviating the hyperglycemic state. We conducted a meta-analysis and systematic review of existing randomized controlled trials (RCTs) to assess the efficacy of FMT in T2DM.<br><br>METHODS: We conducted a computer search of PubMed, Embase, The Cochrane Library, and Web of Science to screen randomized controlled trials studies on FMT treatment for T2DM and extracted data from studies that met inclusion criteria. RevMan 5.4 software and Stata 11 software was used for meta-analysis. The indexes of Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial blood glucose (PBG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), body mass index (BMI), Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) were mainly evaluated after FMT treatment of T2DM patients, and the changes of intestinal flora were evaluated.<br><br>RESULTS: Four RCTs met the inclusion criteria and were included in the meta-analysis. Results of the meta-analysis showed that compared with the non-FMT group, FMT combined treatment could significantly reduce the PBG level in patients with type 2 diabetes (MD&#x2009;=&#x2009;-0.51, 95% CI: -1.42-0.40, P&#x2009;=&#x2009;0.27). Compared with single FMT treatment, FMT combined treatment could reduce TG levels in patients with type 2 diabetes (MD&#x2009;=&#x2009;-0.60, 95% CI: -1.12~-0.07, P&#x2009;=&#x2009;0.03). The levels of TG (MD&#x2009;=&#x2009;-0.26, 95% CI: -0.51~-0.02, P&#x2009;=&#x2009;0.03), HOMA-IR (MD&#x2009;=&#x2009;-2.73, 95% CI: -4.71~0.75, P&#x2009;=&#x2009;0.007) and HDL (MD&#x2009;=&#x2009;-0.06,95% CI: -0.10~-0.02, P&#x2009;=&#x2009;0.003) were significantly decreased after treatment in the single FMT group. The level of TC (MD&#x2009;=&#x2009;-0.65, 95% CI: -1.00~-0.31, P&#x2009;=&#x2009;0.0002) was significantly decreased after FMT combined treatment. Compared with before treatment, ALT (MD&#x2009;=&#x2009;-2.52, 95% CI: -3.86~-1.17, P&#x2009;=&#x2009;0.0002) and DBP (MD&#x2009;=&#x2009;-2, 95% CI: -3.32~0.68, P&#x2009;=&#x2009;0.003) levels decreased after treatment in the single FMT group and the FMT combined group. FPG (MD&#x2009;=&#x2009;-0.94, 95% CI: -1.86~-0.02, P&#x2009;=&#x2009;0.04), TG (MD&#x2009;=&#x2009;-0.73, 95% CI: -1.42~-0.04, P&#x2009;=&#x2009;0.04) and TC (MD&#x2009;=&#x2009;-0.94, 95% CI: -1.45~-0.43, P&#x2009;=&#x2009;0.0003) were significantly decreased after combined drug and diet therapy. Secondly, FMT can promote the colonization and growth of donor-related flora in patients with type 2 diabetes.<br><br>CONCLUSION: In patients with type 2 diabetes mellitus, FMT treatment can reduce the levels of PBG, TG, HOMA-IR, TC, ALT, and DBP, especially in the combined treatment regimen. In addition, FMT can reshape the intestinal flora and establish the balance of dominant flora.}, }
@article {pmid38000189, year = {2023}, author = {de-Mendoza, C and Pérez, L and Rando, A and Reina, G and Aguilera, A and Benito, R and Eirós, JM and Rodríguez-Avial, I and Ortega, D and Pozuelo, MJ and Pena, MJ and Soriano, V and , }, title = {HTLV-1-associated myelopathy in Spain.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {169}, number = {}, pages = {105619}, doi = {10.1016/j.jcv.2023.105619}, pmid = {38000189}, issn = {1873-5967}, mesh = {Middle Aged ; Humans ; Female ; *Paraparesis, Tropical Spastic/epidemiology/diagnosis ; Spain/epidemiology ; Leukocytes, Mononuclear ; *HTLV-I Infections/epidemiology/diagnosis ; *Human T-lymphotropic virus 1/genetics ; Viral Load ; }, abstract = {BACKGROUND: HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1 carriers develop HTLV-1-associated myelopathy (HAM), a progressive subacute neurological disabling disease.<br><br>METHODS: We report the main features of patients diagnosed with HAM up to date in Spain, a non-endemic country with a relatively high migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic.<br><br>RESULTS: A total of 451 cases of HTLV-1 had been recorded in Spain until the end of year 2022. HAM had been diagnosed in 58 (12.9%). The current incidence is of 2-3 new cases per year. Women represent 76%. Mean age at diagnosis is 49 years-old. Nearly 60% are Latin Americans. Although sexual transmission is the most likely route of HTLV-1 acquisition, up to 6 individuals had been infected following solid organ transplantation. Rapid onset myelopathy developed in all but one of these transplant recipients from three HTLV-1-positive donors. HTLV-1 subtype 1a transcontinental was the only variant recognized in HAM patients. HTLV-1 proviral load was significantly greater in HAM patients than in asymptomatic HTLV-1 carriers (677&#xa0;vs 104 HTLV-1 DNA copies/10[4] PBMC; p&#xa0;=&#xa0;0.012). Symptom relief medications and physiotherapy have been the only treatment providing some benefit to HAM patients. Neither significant clinical nor virological efficacy was noticed using antiretrovirals in at least 9 HAM patients. Two thirds of HAM patients ended up in a wheelchair and with urinary/fecal sphincter incontinence.<br><br>CONCLUSION: HAM is the most frequent clinical manifestation of HTLV-1 infection in Spain, a non-endemic country. Middle aged women migrants from Latin America are the most frequently affected. Two thirds end up in a wheelchair despite using antiretroviral therapy.}, }
@article {pmid37999101, year = {2023}, author = {Duttagupta, S and Hakozaki, T and Routy, B and Messaoudene, M}, title = {The Gut Microbiome from a Biomarker to a Novel Therapeutic Strategy for Immunotherapy Response in Patients with Lung Cancer.}, journal = {Current oncology (Toronto, Ont.)}, volume = {30}, number = {11}, pages = {9406-9427}, pmid = {37999101}, issn = {1718-7729}, mesh = {Humans ; *Lung Neoplasms/drug therapy ; *Gastrointestinal Microbiome ; *Carcinoma, Non-Small-Cell Lung/drug therapy ; Immunotherapy ; Biomarkers ; }, abstract = {The gastrointestinal microbiome has been shown to play a key role in determining the responses to cancer immunotherapy, including immune checkpoint inhibitor (ICI) therapy and CAR-T. In patients with non-small cell lung cancer (NSCLC), increasing evidence suggests that a microbiome composition signature is associated with clinical response to ICIs as well as with the development of immune-related adverse events. In support of this, antibiotic (ATB)-related dysbiosis has been consistently linked with the deleterious impact of ICI response, shortening the overall survival (OS) among patients on ATBs prior to ICI initiation. In parallel, several preclinical experiments have unravelled various strategies using probiotics, prebiotics, diet, and fecal microbiota transplantation as new therapeutic tools to beneficially shift the microbiome and enhance ICI efficacy. These approaches are currently being evaluated in clinical trials and have achieved encouraging preliminary results. In this article, we reviewed the recent studies on the gut microbiome as a potential biomarker and an adjuvant therapy to ICIs in NSCLC patients.}, }
@article {pmid37998819, year = {2023}, author = {DuPont, HL and Salge, MMH}, title = {The Importance of a Healthy Microbiome in Pregnancy and Infancy and Microbiota Treatment to Reverse Dysbiosis for Improved Health.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {37998819}, issn = {2079-6382}, abstract = {BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.<br><br>METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).<br><br>RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during pregnancy, cesarean delivery, prematurity, and formula feeding contribute to dysbiosis in the newborn. Microbiota therapy is an important approach to repair dysbiosis in pregnant women and their infants. Currently available probiotics can have favorable metabolic effects on mothers and infants, but these effects are variable. In research settings, reversal of infant dysbiosis can be achieved via vaginal seeding or FMT. Next generation probiotics in development should replace current probiotics and FMT.<br><br>CONCLUSIONS: The most critical phase of human microbiome development is in the first 2-3 years of life. Preventing and treating dysbiosis during pregnancy and early life can have a profound effect on an infant's later health.}, }
@article {pmid37996087, year = {2024}, author = {Chen, YF and Li, SC and Huang, EY}, title = {Role of microbiota in radiation-induced small-bowel damage.}, journal = {Journal of radiation research}, volume = {65}, number = {1}, pages = {55-62}, pmid = {37996087}, issn = {1349-9157}, support = {CORPG8K0161//Kaohsiung Chang Gung Medical Research Project/ ; }, mesh = {Humans ; Mice ; Animals ; *Galectin 1/pharmacology ; Interleukin-6/pharmacology ; Cytokine Receptor gp130 ; Quality of Life ; Intestine, Small ; *Gastrointestinal Microbiome ; }, abstract = {Radiation-induced gastrointestinal damage is a common acute radiation syndrome. Previous studies have highlighted that Galectin-1 and Interleukin-6 (IL-6) are associated with flaking of small intestinal villi and intestinal radioresistance. Therefore, our goal is to study whether gut bacteria regulated by galectin-1 or IL-6 can mitigate radiation-induced small intestine damage. In this study, differences between galectin-1, sgp130-regulated and wild-type (WT) mice were analyzed by microbiome array. The effects of the Firmicutes/Bacteroidetes (F/B) ratio and the proportion of bacterial distribution at the phylum level were observed after 18 Gy whole abdomen radiation. Fecal microbiota transplantation was used to implant radioresistant gut flora into WT mice, and the number of viable small intestinal crypt foci was observed by immunohistochemistry. Fecal transplantation from galectin-1 knockout and sgp130 transgenic mice, with higher radiation resistance, into WT mice significantly increased the number of surviving small intestinal crypts. This radiation resistance, generated through gene regulation, was not affected by the F/B ratio. We initially found that the small intestinal villi of WT mice receiving radioresistant mouse fecal bacteria demonstrated better repair outcomes after radiation exposure. These results indicate the need for a focus on the identification and application of superior radioresistant bacterial strains. In our laboratory, we will further investigate specific radioresistant bacterial strains to alleviate acute side effects of radiation therapy to improve the patients' immune ability and postoperative quality of life.}, }
@article {pmid37995723, year = {2024}, author = {Distante, M and Rotulo, S and Ranalli, M and Pedace, E and Lionetti, P and Arrigo, S and Alvisi, P and Miele, E and Martinelli, M and Zuin, G and Bramuzzo, M and Cananzi, M and Aloi, M and , }, title = {Clusters of Disease Activity and Early Risk Factors of Clinical Course of Pediatric Crohn's Disease.}, journal = {Inflammatory bowel diseases}, volume = {30}, number = {11}, pages = {1983-1991}, doi = {10.1093/ibd/izad275}, pmid = {37995723}, issn = {1536-4844}, mesh = {Humans ; *Crohn Disease/complications/pathology ; Male ; Female ; Child ; Adolescent ; Risk Factors ; Prognosis ; Follow-Up Studies ; *Disease Progression ; *Severity of Illness Index ; Registries ; Italy/epidemiology ; Feces/chemistry ; Leukocyte L1 Antigen Complex/analysis ; }, abstract = {BACKGROUND: This study aimed to define clusters of disease activity and prognostic factors of disease course in a well-characterized cohort of children with Crohn's disease (CD).<br><br>METHODS: All patients from the SIGENP IBD (Italian Society of Pediatric Gastroenterology Hepatology and Nutrition Inflammatory Bowel Disease) registry with a 5-year follow-up and 6-monthly evaluation were included. Active disease was defined for each semester as follows: clinical activity (weighted Pediatric Crohn's Disease Activity Index &#x2265;12.5 or Mucosal Inflammation Noninvasive Index &#x2265;8) and active disease on endoscopy (Simple Endoscopic Score for Crohn's Disease >3 or fecal calprotectin >250 &#xb5;g/g) or imaging. Formula-based clusters were generated based on previously published patterns in adults.<br><br>RESULTS: Data from 332 patients were analyzed. A total of 105 (32%) experienced a quiescent disease course; 49 (15%) and 31 (9%) a moderate-to-severe chronically active and chronic intermittent disease, respectively; 104 (31%) and 43 (13%) had active disease in the first 2 years after diagnosis and remission thereafter and vice versa, respectively. Surgery at diagnosis was significantly associated with a quiescent course (odds ratio [OR], 10.05; 95% confidence interval [CI], 3.05-25.22; P=.0005), while growth impairment at the diagnosis and active disease requiring corticosteroids at 6 months were inversely related to the quiescent group (OR, 0.48; 95% CI, 0.27-0.81; P= .007; and OR, 0.35; 95% CI, 0.16-0.71; P= .005, respectively). Perianal involvement at diagnosis and moderate-severe activity at 6 months correlated with disease progression (OR, 3.85; 95% CI, 1.20-12.85; P=.02).<br><br>CONCLUSIONS: During the first 5 years of follow-up, one-third of children with CD experience a quiescent course. However, another one-third have a moderate-to-severe disease course. Surgery at the diagnosis is related to a quiescent course, while growth impairment and lack of response to induction therapy correlate with more severe disease activity during follow-up.}, }
@article {pmid37993541, year = {2023}, author = {Li, Z and Zhang, X and Wu, H and Ma, Z and Liu, X and Ma, J and Zhang, D and Sheng, L and Chen, X and Zhang, S}, title = {Hydrangea paniculata coumarins attenuate experimental membranous nephritis by bidirectional interactions with the gut microbiota.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {1189}, pmid = {37993541}, issn = {2399-3642}, mesh = {Rats ; Animals ; *Gastrointestinal Microbiome ; Coumarins/pharmacology ; *Hydrangea ; Dysbiosis ; *Endotoxemia ; *Nephritis ; }, abstract = {Coumarins isolated from Hydrangea paniculata (HP) had a renal protective effect in experimental membranous nephritis (MN), but the mechanisms are not clear. Currently, we investigate whether the modulation of gut dysbiosis by HP contributes to its renal protection. Experimental MN rats were treated with HP for six weeks. Fecal 16S rDNA sequencing and metabolomics were performed. Fecal microbiota transplantation (FMT) was used for the evaluation study. The results demonstrate that deteriorated renal function and gut dysbiosis are found in MN rats, as manifested by a higher Firmicutes/Bacteroidetes ratio and reduced diversity and richness, but both changes were reversed by HP treatment. Reduced gut dysbiosis is correlated with improved colonic integrity and lower endotoxemia in HP-treated rats. HP normalized the abnormal level of fecal metabolites by increasing short-chain fatty acid production and hindering the production of uremic toxin precursors. FMT of HP-treated feces to MN animals moderately reduced endotoxemia and albuminuria. Moreover, major coumarins in HP were only biotransformed into more bioactive 7-hydroxycoumarin by gut microbiota, which strengthened the effect of HP in vivo. Depletion of the gut microbiota partially abolished its renal protective effect. In conclusion, the bidirectional interaction between HP and the gut microbiota contributes to its beneficial effect.}, }
@article {pmid37992712, year = {2023}, author = {Zhang, C and Yu, L and Ma, C and Jiang, S and Zhang, Y and Wang, S and Tian, F and Xue, Y and Zhao, J and Zhang, H and Liu, L and Chen, W and Huang, S and Zhang, J and Zhai, Q}, title = {A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation.}, journal = {Cell host &amp; microbe}, volume = {31}, number = {12}, pages = {1989-2006.e8}, doi = {10.1016/j.chom.2023.10.011}, pmid = {37992712}, issn = {1934-6069}, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome ; Constipation/therapy/microbiology ; Polysaccharides ; *Probiotics/therapeutic use ; }, abstract = {Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics, such as Bifidobacteria, can improve this bowel disorder; however, efficacy is strain-dependent. We determine that a genetic factor, the abfA cluster governing arabinan utilization, in Bifidobacterium longum impacts treatment efficacy against functional constipation (FC). In mice with FC, B. longum, but not an abfA mutant, improved gastrointestinal transit time, an affect that was dependent upon dietary arabinan. abfA genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly abfA-dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with abfA-cluster-carrying B. longum, but not an abfA-deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, abfA-cluster abundance can predict FC, and transplantation of abfA cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial abfA cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies.}, }
@article {pmid37992400, year = {2023}, author = {Qian, X and Hai, W and Chen, S and Zhang, M and Jiang, X and Tang, H}, title = {Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP/PS1 mice.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2282790}, pmid = {37992400}, issn = {1949-0984}, mesh = {Mice ; Animals ; Amyloid beta-Protein Precursor/genetics/metabolism ; Mice, Transgenic ; Neuroinflammatory Diseases ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Multiomics ; Positron Emission Tomography Computed Tomography ; *Alzheimer Disease/complications ; Glycerophospholipids ; Disease Models, Animal ; }, abstract = {Numerous studies have described the notable impact of gut microbiota on the brain in Alzheimer's disease (AD) via the gut - brain axis. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of AD are limited. This study aimed to explore the potential mechanisms of gut microbiota in AD by integrating multi-omics data. In this study, APP/PS1 and WT mice at nine months of age were used as study mouse model. Cognitive function was assessed using the Morris water maze test. The levels of Aβ plaque and neuroinflammation in the brain were detected using immunofluorescence and PET/CT. In addition, we not only used 16S rRNA gene sequencing and metabolomics to explore the variation characteristics of gut microbiota and serum metabolism abundance, but also combined spatial metabolomics and transcriptomics to explore the change in the brain and identify their potential correlation. APP/PS1 mice showed significant cognitive impairment and amyloid-β deposits in the brain. The abundance of gut microbiota was significantly changed in APP/PS1 mice, including decreased Desulfoviobrio, Enterococcus, Turicibacter, and Ruminococcus and increased Pseudomonas. The integration of serum untargeted metabolomics and brain spatial metabolomics showed that glycerophospholipid metabolism was a common alteration pathway in APP/PS1 mice. Significant proliferation and activation of astrocyte and microglia were observed in APP/PS1 mice, accompanied by alterations in immune pathways. Integration analysis and fecal microbiota transplantation (FMT) intervention revealed potential association of gut microbiota, host glycerophospholipid metabolism, and neuroinflammation levels in APP/PS1 mice.}, }
@article {pmid37992054, year = {2023}, author = {Zhang, M and Yang, T and Li, R and Ren, K and Li, J and He, M and Chen, J and Yi, SQ}, title = {Gut microbiota of Suncus murinus, a naturally obesity-resistant animal, improves the ecological diversity of the gut microbiota in high-fat-diet-induced obese mice.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0293213}, pmid = {37992054}, issn = {1932-6203}, mesh = {Humans ; Animals ; Mice ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Mice, Obese ; RNA, Ribosomal, 16S/genetics ; Ecosystem ; Mice, Inbred C57BL ; Obesity/etiology/therapy/metabolism ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/pharmacology ; }, abstract = {BACKGROUND: The global population of obese individuals is increasing, affecting human health. High-fat diets are a leading cause of this epidemic, and animal models, such as mice, are often used in related research. Obese individuals have a different gut microbiota composition from non-obese ones, characterized by a sizeable population of certain bacteria associated with fat storage. The gut microbiome plays a significant role in regulating human physiological and metabolic functions. Links between obesity, high-fat diets and gut microbiota have become hot topics of discussion. Recently, research on the modulation of the gut microbiota has focused on fecal microbiota transplantation (FMT), which has been recognized as an effective method of studying the function of gut microbiota.<br><br>OBJECTIVES: The purpose of this study was to investigate how the gut microbiota of Suncus murinus, a naturally obesity-resistant animal, through FMT, affected the ecology of the gut microbiota of high-fat diet induced obese mice.<br><br>METHODS: In this study, Suncus murinus was used as a donor for FMT. High-fat diet induced C57BL/6NCrSIc mice were used as recipients, the body weight changes were measured and changes in their gut flora were analyzed using a 16S rRNA gene analysis.<br><br>RESULTS: The study found that, after the FMT procedure, the FMT group tended to have a lower body weight than the control group. At the phylum level, the most predominant phyla in all groups were Firmicutes and Proteobacteria, while Deferribacteres was not detected in the FMT or antibiotic administration groups, and Bacteroidetes was not present in the antibiotic administration group. At the genus level, the FMT group had significantly lower OTU richness than the control group but greater diversity than the control group.<br><br>CONCLUSIONS: These results indicate that FMT from Suncus murinus can help reorganize and improve the gut microbiota of mice in a balanced and diverse ecosystem.}, }
@article {pmid37990909, year = {2023}, author = {Boatman, S and Kaiser, T and Nalluri-Butz, H and Khan, MH and Dietz, M and Kohn, J and Johnson, AJ and Gaertner, WB and Staley, C and Jahansouz, C}, title = {Diet-induced shifts in the gut microbiota influence anastomotic healing in a murine model of colonic surgery.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2283147}, pmid = {37990909}, issn = {1949-0984}, mesh = {Mice ; Humans ; Animals ; *Gastrointestinal Microbiome ; Disease Models, Animal ; Colon/surgery/microbiology ; Anastomosis, Surgical/adverse effects ; Fecal Microbiota Transplantation/methods ; Anastomotic Leak/microbiology ; Diet, Western/adverse effects ; }, abstract = {Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia. We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.}, }
@article {pmid37988085, year = {2024}, author = {Zhang, S and Huang, Y and Lu, G and Zhang, Z and Wang, Y and Liu, Y and Wang, W and Li, Q and Li, P and Wen, Q and Cui, B and Zhang, F}, title = {Comparison between washed microbiota transplantation and infliximab: Medical cost during long-term management in patients with inflammatory bowel disease.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {87}, number = {1}, pages = {109-118}, doi = {10.1097/JCMA.0000000000001025}, pmid = {37988085}, issn = {1728-7731}, mesh = {Humans ; Infliximab/therapeutic use/adverse effects ; Mesalamine ; *Inflammatory Bowel Diseases/therapy/chemically induced ; Hospitalization ; *Microbiota ; }, abstract = {BACKGROUND: Both infliximab (IFX) and fecal microbiota transplantation (FMT) have shown the efficacy for inflammatory bowel disease (IBD). However, there has no head-to-head study on the cost-value of the such treatments on IBD. This study aimed to compare the medical costs using IFX and the new method of FMT (washed microbiota transplantation [WMT]) in the long-term management for IBD under the current health economic condition in China.<br><br>METHODS: Patients with IBD who underwent initial WMT via upper gastrointestinal endoscopy, mid-gut tube, or colonic transendoscopic enteral tubing at a university hospital between April 2013 and August 2021 and achieved the long-term sustainment with WMT or WMT combined with mesalazine until August 2022 were recruited in the real-world. The costs and hospitalizations were analyzed among two therapies mentioned above and IFX standard therapy. The charge of WMT was stable in the long term at our center, and the charge of IFX came from virtual statistics publicized by China Healthcare Security.<br><br>RESULTS: Sixty eligible patients with IBD were included in the study. The long-term costs of patients using WMT monotherapy annually or per hospitalization were lower than those on WMT combined with mesalazine, respectively (p < 0.001, respectively). The cumulative costs of IFX at the time of 0.52 and 0.85 years exceeded that of the above WMT, respectively (p < 0.001, respectively). Besides, patients on WMT monotherapy paid 51.1 k CNY annually in the nonsustain phase but cut down the costs by 7.2 k CNY and duration of hospitalization by 5.1 days per hospitalization when reaching the goal of sustainment.<br><br>CONCLUSION: This study demonstrated that WMT could dramatically reduce the cost and duration of hospitalizations in the long-term sustainment in the current Chinese IBD cohort. Compared with IFX, WMT could be a good way for the patients with IBD achieving long-term sustainment and saving medical costs.}, }
@article {pmid37986824, year = {2024}, author = {Berryhill, BA and Burke, KB and Fontaine, J and Brink, CE and Harvill, MG and Goldberg, DA and Konstantinidis, KT and Levin, BR and Woodworth, MH}, title = {Enteric Populations of Escherichia coli are Likely to be Resistant to Phages Due to O Antigen Expression.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37986824}, issn = {2692-8205}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; R35 GM136407/GM/NIGMS NIH HHS/United States ; }, abstract = {There is a surfeit of bioinformatic data showing that bacteriophages abound in the enteric microbiomes of humans. What is the contribution of these viruses in shaping the bacterial strain and species composition of the gut microbiome and how are these phages maintained over time? To address these questions, we performed experiments with Escherichia coli and phages isolated from four fecal microbiota transplantation (FMT) doses as representative samples of non-dysbiotic enteric microbiota and develop and analyze the properties of a mathematical model of the population and evolutionary dynamics of bacteria and phage. Our models predict and experiments confirm that due to production of the O antigen, E. coli in the enteric microbiome are likely to be resistant to infection with co-occurring phages. Furthermore, our modeling suggests that the phages can be maintained in the population due to the high rates of host transition between resistant and sensitive states, which we call leaky resistance. Based on our observations and model predictions, we postulate that the phages found in the human gut are likely to play little role in shaping the composition of E. coli at the strain level in the enteric microbiome in healthy individuals. How general this is for other species of bacteria in the enteric flora is not yet clear, although O antigen expression is common across many taxa.}, }
@article {pmid37981872, year = {2023}, author = {Oliva-Hemker, M and Kahn, SA and Steinbach, WJ and ,  and , }, title = {Fecal Microbiota Transplantation: Information for the Pediatrician.}, journal = {Pediatrics}, volume = {152}, number = {6}, pages = {}, doi = {10.1542/peds.2023-062922}, pmid = {37981872}, issn = {1098-4275}, mesh = {Child ; Humans ; Fecal Microbiota Transplantation ; Feces ; *Autism Spectrum Disorder ; *Inflammatory Bowel Diseases/therapy ; Pediatricians ; *Clostridium Infections/therapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) involves the delivery of an entire microbial community from a healthy donor to a recipient with the intention of ameliorating or curing a specific disease. Current evidence strongly supports a role for FMT in the treatment of Clostridiodes difficile infection, with cure rates of approximately 80% to 90%. This success has led to increasing attention for FMT as a potential therapeutic intervention for other conditions associated with disturbances of the intestinal microbiome, including inflammatory bowel diseases, autism spectrum disorder, and obesity. This clinical report endorses the joint society statement by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition and is meant to provide the general pediatrician with a broad overview to enable appropriate guidance to families seeking FMT as treatment of a child's condition.}, }
@article {pmid37981746, year = {2024}, author = {Arora, U and Kedia, S and Ahuja, V}, title = {The practice of fecal microbiota transplantation in inflammatory bowel disease.}, journal = {Intestinal research}, volume = {22}, number = {1}, pages = {44-64}, pmid = {37981746}, issn = {1598-9100}, abstract = {Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.}, }
@article {pmid37981012, year = {2024}, author = {Zheng, M and Ye, H and Yang, X and Shen, L and Dang, X and Liu, X and Gong, Y and Wu, Q and Wang, L and Ge, X and Fang, X and Hou, B and Zhang, P and Tang, R and Zheng, K and Huang, XF and Yu, Y}, title = {Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis.}, journal = {Brain, behavior, and immunity}, volume = {115}, number = {}, pages = {565-587}, doi = {10.1016/j.bbi.2023.11.016}, pmid = {37981012}, issn = {1090-2139}, mesh = {Humans ; Animals ; Mice ; Brain-Gut Axis ; *Clostridium butyricum ; Dysbiosis/complications ; Mice, Obese ; *Neurodegenerative Diseases ; Obesity/complications ; *Cognitive Dysfunction/etiology ; *Probiotics/pharmacology ; }, abstract = {Obesity is a risk factor for cognitive dysfunction and neurodegenerative disease, including Alzheimer's disease (AD). The gut microbiota-brain axis is altered in obesity and linked to cognitive impairment and neurodegenerative disorders. Here, we targeted obesity-induced cognitive impairment by testing the impact of the probiotic Clostridium butyricum, which has previously shown beneficial effects on gut homeostasis and brain function. Firstly, we characterized and analyzed the gut microbial profiles of participants with obesity and the correlation between gut microbiota and cognitive scores. Then, using an obese mouse model induced by a Western-style diet (high-fat and fiber-deficient diet), the effects of Clostridium butyricum on the microbiota-gut-brain axis and hippocampal cognitive function were evaluated. Finally, fecal microbiota transplantation was performed to assess the functional link between Clostridium butyricum remodeling gut microbiota and hippocampal synaptic protein and cognitive behaviors. Our results showed that participants with obesity had gut microbiota dysbiosis characterized by an increase in phylum Proteobacteria and a decrease in Clostridium butyricum, which were closely associated with cognitive decline. In diet-induced obese mice, oral Clostridium butyricum supplementation significantly alleviated cognitive impairment, attenuated the deficit of hippocampal neurite outgrowth and synaptic ultrastructure, improved hippocampal transcriptome related to synapses and dendrites; a comparison of the effects of Clostridium butyricum in mice against human AD datasets revealed that many of the genes changes in AD were reversed by Clostridium butyricum; concurrently, Clostridium butyricum also prevented gut microbiota dysbiosis, colonic barrier impairment and inflammation, and attenuated endotoxemia. Importantly, fecal microbiota transplantation from donor-obese mice with Clostridium butyricum supplementation facilitated cognitive variables and colonic integrity compared with from donor obese mice, highlighting that Clostridium butyricum's impact on cognitive function is largely due to its ability to remodel gut microbiota. Our findings provide the first insights into the neuroprotective effects of Clostridium butyricum on obesity-associated cognitive impairments and neurodegeneration via the gut microbiota-gut-brain axis.}, }
@article {pmid37979881, year = {2024}, author = {Liang, Y and Liu, D and Li, Y and Hou, H and Li, P and Ma, X and Li, P and Zhan, J and Wang, P}, title = {Maternal polysorbate 80 intake promotes offspring metabolic syndrome through vertical microbial transmission in mice.}, journal = {The Science of the total environment}, volume = {909}, number = {}, pages = {168624}, doi = {10.1016/j.scitotenv.2023.168624}, pmid = {37979881}, issn = {1879-1026}, mesh = {Mice ; Animals ; Pregnancy ; Female ; Humans ; *Metabolic Syndrome ; Polysorbates ; Cesarean Section ; Mice, Inbred C57BL ; Pectins ; Mammals ; }, abstract = {Polysorbate 80 (P80) is an emulsifier extensively produced, consumed and discharged into the environment, consequently making human exposure inevitable. Despite evidence suggesting that P80 intake causes metabolic syndrome (MS) in mammals via microbial perturbation, limited data exist on its transgenerational impacts on offspring. In this study, we found that maternal P80 treatment impaired intestinal barrier integrity, leading to metabolic endotoxemia, low-grade inflammation and MS-related symptoms in C57BL/6J female offspring. Further analysis of the gut microbiome revealed MS-related changes in the offspring of P80-treated dams. Fecal microbiota transplantation experiment confirmed the crucial role of the altered microbiome in offspring in the transgenerational impacts of P80. Furthermore, we found that the P80-induced microbial alterations were directly transmitted from P80-treated mothers to their offspring and that interrupting vertical microbial transmission through cesarean section and foster nursing blocked the transgenerational impacts of P80 on the offspring microbiome and metabolic health. Moreover, maternal pectin supplementation also effectively mitigated P80-induced microbial alterations and MS-associated phenotypes in offspring. Together, our results indicated that maternal P80 intake could impair offspring metabolic health through the mother-to-offspring transmission of the microbiome, and maternal pectin supplementation might be a promising strategy for reducing the adverse effects of P80.}, }
@article {pmid37979452, year = {2024}, author = {Xi, D and Liu, P and Feng, Y and Teng, Y and Liang, Y and Zhou, J and Deng, H and Zeng, G and Zong, S}, title = {Fecal microbiota transplantation regulates the microbiota-gut-spinal cord axis to promote recovery after spinal cord injury.}, journal = {International immunopharmacology}, volume = {126}, number = {}, pages = {111212}, doi = {10.1016/j.intimp.2023.111212}, pmid = {37979452}, issn = {1878-1705}, mesh = {Humans ; Rats ; Animals ; Fecal Microbiota Transplantation ; Interleukin-17/pharmacology ; *Gastrointestinal Microbiome ; Dysbiosis/therapy ; *Spinal Cord Injuries/therapy ; }, abstract = {Spinal cord injury (SCI) is devastating for patients, and currently lacks effective treatments. Dysbiosis commonly occurs after SCI and has significant immunomodulatory effects, but its impact on recovery remains unclear. The current study investigated the effects and mechanisms of fecal microbiota transplantation (FMT) in SCI. FMT was administered in a rat model of SCI and spinal pathology, inflammatory cytokines, and gut microbiome composition were assessed. Flow cytometry identified a source of interleukin (IL)-17 in spinal cord tissues, and carboxyfluorescein succimidyl ester labeling tracked γδ T cell migration. In vitro coculture was used to analyze the regulatory mechanisms of γδ T cells. Seahorse analysis was used to profile dendritic cell (DC) metabolism. Here we show that FMT improved spinal pathology and dampened post-injury inflammation. It also corrected post-SCI dysbiosis, increasing levels of the beneficial bacterium Akkermansia. The therapeutic effects of FMT were mediated by IL-17 produced by γδ T cells. FMT regulated γδ T cells via DC-T regulatory cell interaction, and induced metabolic reprogramming in DCs. These findings suggest that FMT represents a promising therapeutic approach for SCI, with potential to target IL-17[+] γδ T cells. Elucidating the interconnected pathways between microbiota, immunity, and the spinal cord may facilitate novel treatment strategies.}, }
@article {pmid37979154, year = {2023}, author = {Kujawa, D and Laczmanski, L and Budrewicz, S and Pokryszko-Dragan, A and Podbielska, M}, title = {Targeting gut microbiota: new therapeutic opportunities in multiple sclerosis.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2274126}, pmid = {37979154}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Multiple Sclerosis/therapy ; *Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Diet ; Dysbiosis ; Prebiotics ; }, abstract = {Multiple sclerosis (MS) causes long-lasting, multifocal damage to the central nervous system. The complex background of MS is associated with autoimmune inflammation and neurodegeneration processes, and is potentially affected by many contributing factors, including altered composition and function of the gut microbiota. In this review, current experimental and clinical evidence is presented for the characteristics of gut dysbiosis found in MS, as well as for its relevant links with the course of the disease and the dysregulated immune response and metabolic pathways involved in MS pathology. Furthermore, therapeutic implications of these investigations are discussed, with a range of pharmacological, dietary and other interventions targeted at the gut microbiome and thus intended to have beneficial effects on the course of MS.}, }
@article {pmid37976078, year = {2024}, author = {Wang, Y and Wang, Z and Lu, Q}, title = {Microbiome dynamics in rheumatic diseases.}, journal = {Current opinion in rheumatology}, volume = {36}, number = {2}, pages = {134-141}, doi = {10.1097/BOR.0000000000000993}, pmid = {37976078}, issn = {1531-6963}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; *Rheumatic Diseases/drug therapy ; *Probiotics/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: Rheumatic disease are characterized by their autoimmune nature, frequently affecting joints, bones, muscles, blood vessels, and connective tissues. The onset of these conditions typically unfolds gradually and subtly. It is noteworthy that individuals with rheumatic diseases often experience shifts in their microbiome, specifically on mucosal surfaces. The purpose of this review is to delve into the intricate interplay between the microbiome, encompassing bacteria, viruses and fungi, and its role in the development and aggravation of various rheumatic diseases. Additionally, it aims to offer insights into microbiome-centered therapeutic approaches for patients in the field of rheumatology.<br><br>RECENT FINDINGS: The advent of next-generation sequencing has significantly improved our understanding of microbiome changes. Numerous studies have consistently revealed a strong link between rheumatism and the microbiome, especially in the oral and gut microbiota.<br><br>SUMMARY: A deeper comprehension of the microbiome's connection to rheumatism holds potential for enhancing disease diagnosis and treatment. Targeted therapeutic approaches, including probiotics, fecal microbiota transplantation, and combination therapies with medications, offer promising avenues for disease management.}, }
@article {pmid37975092, year = {2023}, author = {Guo, J and Zhou, B and Niu, Y and Liu, L and Yang, L}, title = {Engineered probiotics introduced to improve intestinal microecology for the treatment of chronic diseases: present state and perspectives.}, journal = {Journal of diabetes and metabolic disorders}, volume = {22}, number = {2}, pages = {1029-1038}, pmid = {37975092}, issn = {2251-6581}, abstract = {PURPOSE: Correcting intestinal microecological imbalance has become one of the core strategies to treat chronic diseases. Some traditional microecology-based therapies targeting intestine, such as prebiotic therapy, probiotic therapy and fecal microbiota transplantation therapy, have been used in the prevention and treatment of clinical chronic diseases, which still facing low safety and poor controllability problems. The development of synthetic biology technology has promoted the development of intestinal microecology-based therapeutics for chronic diseases, which exhibiting higher robustness and controllability, and become an important part of the next generation of microecological therapy. The purpose of this review is to summarize the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases.<br><br>METHODS: The available literatures were searched to find out experimental studies and relevant review articles on the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases from year 1990 to 2023.<br><br>RESULTS: Evidence proposed that synthetic biology has been applied in the intestinal microecology-based therapeutics for chronic diseases, covering metabolic diseases (e.g. diabetes, obesity, nonalcoholic fatty liver disease and phenylketonuria), digestive diseases (e.g. inflammatory bowel disease and colorectal cancer), and neurodegenerative diseases (e.g. Alzheimer's disease and Parkinson's disease).<br><br>CONCLUSION: This review summarizes the application of synthetic biology in intestinal microecology-based therapeutics for major chronic diseases and discusses the opportunities and challenges in the above process, providing clinical possibilities of synthetic biology technology applied in microecological therapies.}, }
@article {pmid37974103, year = {2023}, author = {Khan, FA and Pandupuspitasari, NS and Huang, C and Negara, W and Ahmed, B and Putri, EM and Lestari, P and Priyatno, TP and Prima, A and Restitrisnani, V and Surachman, M and Akhadiarto, S and Darmawan, IWA and Wahyuni, DS and Herdis, H}, title = {Unlocking gut microbiota potential of dairy cows in varied environmental conditions using shotgun metagenomic approach.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {344}, pmid = {37974103}, issn = {1471-2180}, mesh = {Female ; Cattle ; Animals ; *Lactation ; Diet/veterinary ; *Gastrointestinal Microbiome ; Milk Proteins ; Gases ; Methane/metabolism ; }, abstract = {Food security and environmental pollution are major concerns for the expanding world population, where farm animals are the largest source of dietary proteins and are responsible for producing anthropogenic gases, including methane, especially by cows. We sampled the fecal microbiomes of cows from varying environmental regions of Pakistan to determine the better-performing microbiomes for higher yields and lower methane emissions by applying the shotgun metagenomic approach. We selected managed dairy farms in the Chakwal, Salt Range, and Patoki regions of Pakistan, and also incorporated animals from local farmers. Milk yield and milk fat, and protein contents were measured and correlated with microbiome diversity and function. The average milk protein content from the Salt Range farms was 2.68%, with an average peak milk yield of 45 litters/head/day, compared to 3.68% in Patoki farms with an average peak milk yield of 18 litters/head/day. Salt-range dairy cows prefer S-adenosyl-L-methionine (SAMe) to S-adenosyl-L-homocysteine (SAH) conversion reactions and are responsible for low milk protein content. It is linked to Bacteroides fragilles which account for 10% of the total Bacteroides, compared to 3% in the Patoki region. The solid Non-Fat in the salt range was 8.29%, whereas that in patoki was 6.34%. Moreover, Lactobacillus plantarum high abundance in Salt Range provided propionate as alternate sink to [H], and overcoming a Methanobrevibacter ruminantium high methane emissions in the Salt Range. Furthermore, our results identified ruminant fecal microbiomes that can be used as fecal microbiota transplants (FMT) to high-methane emitters and low-performing herds to increase farm output and reduce the environmental damage caused by anthropogenic gases emitted by dairy cows.}, }
@article {pmid37969732, year = {2023}, author = {Zeng, X and Liao, Y and Qiao, X and Liang, K and Luo, Q and Deng, M and Liu, Y and Zhang, W and Hong, X and Xiao, Y}, title = {Novel NIR-II fluorescent probes for biliary atresia imaging.}, journal = {Acta pharmaceutica Sinica. B}, volume = {13}, number = {11}, pages = {4578-4590}, pmid = {37969732}, issn = {2211-3835}, abstract = {Biliary atresia is a rare infant disease that predisposes patients to liver transplantation and death if not treated in time. However, early diagnosis is challenging because the clinical manifestations and laboratory tests of biliary atresia overlap with other cholestatic diseases. Therefore, it is very important to develop a simple, safe and reliable method for the early diagnosis of biliary atresia. Herein, a novel NIR-II fluorescence probe, HZL2, with high quantum yield, excellent biocompatibility, low cytotoxicity and rapid excretion through the liver and gallbladder was developed based on the oil/water partition coefficient and permeability. A simple fecal sample after injection of HZL2 can be used to efficiently identify the success of the mouse model of biliary atresia for the first time, allowing for an early diagnosis of the disease. This study not only developed a simple and safe method for the early diagnosis of biliary atresia with great potential in clinical translation but also provides a research tool for the development of pathogenesis and therapeutic medicines for biliary atresia.}, }
@article {pmid37967548, year = {2024}, author = {Naito, Y}, title = {Gut Frailty: Its Concept and Pathogenesis.}, journal = {Digestion}, volume = {105}, number = {1}, pages = {49-57}, pmid = {37967548}, issn = {1421-9867}, mesh = {Humans ; *Frailty/diagnosis/etiology/therapy ; *Probiotics/therapeutic use ; Prebiotics ; *Gastrointestinal Microbiome ; Dysbiosis/complications/therapy ; Constipation ; }, abstract = {BACKGROUND: There is still a considerable gap between average life expectancy and healthy life expectancy in Japan. Recent research has revealed that gut frailty may be a worsening factor for various diseases, a cause of chronic inflammation, and a precursor to frailty.<br><br>SUMMARY: Among self-reported symptoms, constipation is particularly significant as one of the key symptoms of gut frailty. Studies have demonstrated that individuals with constipation have significantly lower survival rates and are also at a higher risk of developing various diseases such as chronic kidney disease, cardiovascular diseases, and neurodegenerative disorders like Parkinson's disease. Various molecular mechanisms could contribute to gut frailty, and the decrease in mucus secretion is an extremely early-stage pathology. Dysbiosis of gut microbiota has a major impact on many conditions associated with gut frailty. Prebiotics, probiotics, post-biotics, and fecal microbiota transplantation are under investigation as a treatment option for gut frailty.<br><br>KEY MESSAGE: Although the concept of gut frailty has not yet gained widespread recognition, we hope to propose more practical screening methods, diagnostic approaches, and specific interventions in the future.}, }
@article {pmid37966684, year = {2024}, author = {An, S and Zhen, Z and Wang, S and Sang, M and Zhang, S}, title = {Intestinal Microbiota Is a Key Target for Load Swimming to Improve Anxiety Behavior and Muscle Strength in Shank 3[-/-] Rats.}, journal = {Molecular neurobiology}, volume = {61}, number = {12}, pages = {9961-9976}, pmid = {37966684}, issn = {1559-1182}, support = {7232239//Beijing Municipal Natural Science Foundation/ ; 21BTY023//National Social Science Fund of China/ ; 19YTA007//Key project of Beijing Social Science Foundation/ ; BNUXKJC2110//BNU Interdisciplinary Research Foundation for the First-Year Doctoral Candidates/ ; 20YJA890036//Research and planning fund for Humanities and social sciences of the Ministry of Education/ ; AEEA2020017//Priority topics of Beijing's 13th five year plan for Educational Science/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Swimming ; *Anxiety/microbiology/physiopathology ; *Muscle Strength/physiology ; Rats ; Male ; Nerve Tissue Proteins/metabolism ; Behavior, Animal/physiology ; Rats, Sprague-Dawley ; }, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social disorder and stereotypical behavior, and its incidence rate is increasing yearly. It is considered that acritical period for the prognosis of young children with ASD exists, thus early treatment is crucial. Swimming, due to its comforting effect, is often used to induce enthusiasm in young children for completing activities and has a good effect in the treatment of ASD, but the effective path of swimming has yet to be reported. The intestinal microbiota of ASD patients and animal models has been reported to be different from that of healthy controls, and these changes may affect the brain environment. Therefore, whether the intestinal microbiota is involved in the treatment of ASD by early swimming is our concern. In this study, we used 8-day old Shank3 gene knockout rats with 8 weeks of early load swimming training and conducted behavioral, small intestine morphology, and intestinal content sequencing after training. The results showed that early load swimming significantly reduced the stereotyped and anxious behaviors of Shank3[-/-] rats, increased their muscle strength, increased the length of intestinal villi and the width of the muscular layer after Shank3 knockout, and affected the abundance of intestinal microorganisms. The abundances with statistical significance were Lactobacillus, Lachnospiraceae, and Alloprevotella. To further confirm the role of intestinal microorganisms in it, we designed a 14-day intestinal stool transplantation experiment. Fecal microbiota transplantation demonstrated that load swimming can significantly reduce the anxiety behavior of Shank3 rats, increase their muscle strength, change the structure of the small intestine, and affect the abundance of intestinal contents. The abundance of Epsilonbateraeota, Prevotella, and Bacteroides significantly changed after transplantation. Our findings confirm the possibility of early load swimming therapy for individuals with ASD and explain that the intestinal microbiota is a key pathway for early exercise therapy for patients with ASD.}, }
@article {pmid37965266, year = {2023}, author = {Piazzesi, A and Pane, S and Russo, A and Del Chierico, F and Francalanci, P and Cotugno, N and Rossi, P and Locatelli, F and Palma, P and Putignani, L}, title = {Case Report: The impact of severe cryptosporidiosis on the gut microbiota of a pediatric patient with CD40L immunodeficiency.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1281440}, pmid = {37965266}, issn = {2235-2988}, mesh = {Animals ; Humans ; Child ; Child, Preschool ; *Cryptosporidiosis/complications/parasitology ; CD40 Ligand ; *Gastrointestinal Microbiome ; *Cryptosporidium/genetics ; Intestines/microbiology ; *Immunologic Deficiency Syndromes/complications ; *Parasites ; *Cryptosporidium parvum ; Bacteria/genetics ; Propionibacterium acnes ; }, abstract = {Cryptosporidium parvum is a protozoan parasite and one of the leading causes of gastroenteritis in the world, primarily affecting very young children and immunocompromised patients. While infection is usually self-limiting, it can become chronic and even lethal in these vulnerable populations, in whom Cryptosporidium treatments are generally ineffective, due to their acting in concert with a functioning immune system. Here, we describe a case of chronic cryptosporidiosis in a European child with severe CD40L immunodeficiency infected with Cryptosporidium parvum of the IIa20G1 subgenotype, a lineage which has thus far only ever been described in the Middle East. After years of on-off treatment with conventional and non-conventional anti-parasitic drugs failed to clear parasitosis, we performed targeted metagenomics to observe the bacterial composition of the patient's gut microbiota (GM), and to evaluate fecal microbiota transplantation (FMT) as a potential treatment option. We found that C. parvum infection led to significant shifts in GM bacterial composition in our patient, with consequent shifts in predicted intestinal functional signatures consistent with a state of persistent inflammation. This, combined with the patient's poor prognosis and increasing parasitic burden despite many rounds of anti-parasitic drug treatments, made the patient a potential candidate for an experimental FMT procedure. Unfortunately, given the many comorbidities that were precipitated by the patient's immunodeficiency and chronic C. parvum infection, FMT was postponed in favor of more urgently necessary liver and bone marrow transplants. Tragically, after the first liver transplant failed, the patient lost his life before undergoing FMT and a second liver transplant. With this case report, we present the first description of how cryptosporidiosis can shape the gut microbiota of a pediatric patient with severe immunodeficiency. Finally, we discuss how both our results and the current scientific literature suggest that GM modulations, either by probiotics or FMT, can become novel treatment options for chronic Cryptosporidium infection and its consequent complications, especially in those patients who do not respond to the currently available anti-parasitic therapies.}, }
@article {pmid37962812, year = {2024}, author = {Lachmansingh, DA and Lavelle, A and Cryan, JF and Clarke, G}, title = {Microbiota-Gut-Brain Axis and Antidepressant Treatment.}, journal = {Current topics in behavioral neurosciences}, volume = {66}, number = {}, pages = {175-216}, pmid = {37962812}, issn = {1866-3370}, mesh = {Humans ; *Brain-Gut Axis/physiology/drug effects ; *Antidepressive Agents/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/physiology/drug effects ; *Probiotics/pharmacology/therapeutic use ; Prebiotics/administration &amp; dosage ; Animals ; Depressive Disorder/therapy/drug therapy/microbiology ; Brain ; }, abstract = {In the treatment of depressive disorders, conventional antidepressant therapy has been the mainstay of clinical management, along with well-established nonpharmacological interventions such as various kinds of psychotherapy. Over the last 2 decades, there has been considerable interest in the role of the gastrointestinal system and its microbiota on brain function, behavior, and mental health. Components of what is referred to as the microbiota-gut-brain axis have been uncovered, and further research has elicited functional capabilities such as "gut-brain modules." Some studies have found associations with compositional alterations of gut microbiota in patients with depressive disorders and individuals experiencing symptoms of depression. Regarding the pathogenesis and neurobiology of depression itself, there appears to be a multifactorial contribution, in addition to the theories involving deficits in catecholaminergic and monoamine neurotransmission. Interestingly, there is evidence to suggest that antidepressants may play a role in modulating the gut microbiota, thereby possibly having an impact on the microbiota-gut-brain axis in this manner. The development of prebiotics, probiotics, and synbiotics has led to studies investigating not only their impact on the microbiota but also their therapeutic value in mental health. These psychobiotics have the potential to be used as therapeutic adjuncts in the treatment of depression. Regarding future directions, and in an attempt to further understand the role of the microbiota-gut-brain axis in depression, more studies such as those involving fecal microbiota transplantation will be required. In addition to recent findings, it is also suggested that more research will have to be undertaken to elicit whether specific strains of gut organisms are linked to depression. In terms of further investigation of the therapeutic potential of prebiotics, probiotics, and synbiotics as adjuncts to antidepressant treatment, we also expect there to be more research targeting specific microorganisms, as well as a strong focus on the effects of specific prebiotic fibers from an individualized (personalized) point of view.}, }
@article {pmid37962207, year = {2024}, author = {Yang, T and Xie, S and Cao, L and Li, M and Ding, L and Wang, L and Pang, S and Wang, Z and Geng, L}, title = {ASTRAGALOSIDE Ⅳ MODULATES GUT MACROPHAGES M1/M2 POLARIZATION BY RESHAPING GUT MICROBIOTA AND SHORT CHAIN FATTY ACIDS IN SEPSIS.}, journal = {Shock (Augusta, Ga.)}, volume = {61}, number = {1}, pages = {120-131}, pmid = {37962207}, issn = {1540-0514}, mesh = {Humans ; Animals ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Inflammasomes/metabolism ; *Gastrointestinal Microbiome ; Caco-2 Cells ; RNA, Ribosomal, 16S/metabolism ; Fatty Acids, Volatile/metabolism ; Butyrates/metabolism ; Inflammation/metabolism ; Macrophages/metabolism ; *Sepsis/metabolism ; Cytokines/metabolism ; *Saponins ; *Triterpenes ; }, abstract = {M1 macrophage-mediated inflammation is critical in sepsis. We previously found the protective role of astragaloside intravenous (AS-IV) in sepsis-associated gut impairment, whose specific mechanism remains unknown. Gut microbiota modulates gut homeostatic balance to avoid excessive inflammation. Here, we aimed to investigate effects of AS-IV on gut macrophages polarization and potential roles of gut microbiota and short chain fatty acids (SCFAs) in septic gut damage. Mice were pretreated by AS-IV gavage for 7 days before cecal ligation and puncture. M1 polarization of gut lamina propria macrophages (LpMs) was promoted by cecal ligation and puncture, accompanied by abnormal cytokines release and intestinal barrier dysfunction. NLRP3 inflammasome was activated in M1 LpMs. 16S rRNA sequencing demonstrated gut microbiota imbalance. The levels of acetate, propionate, and butyrate in fecal samples decreased. Notably, AS-IV reversed LpMs M1/M2 polarization, lightened gut inflammation and barrier injury, reduced NLRP3 inflammasome expression in LpMs, restored the diversity of gut microbiome, and increased butyrate levels. Similarly, these benefits were mimicked by fecal microbiota transplantation or exogenous butyrate supplementation. In Caco-2 and THP-1 cocultured model, LPS and interferon γ caused THP-1 M1 polarization, Caco-2 barrier impairment, abnormal cytokines release, and high NLRP3 inflammasome expression in THP-1 cells, all of which were mitigated by butyrate administration. However, these protective effects of butyrate were abrogated by NLRP3 gene overexpression in THP-1. In conclusion, AS-IV can ameliorate sepsis-induced gut inflammation and barrier dysfunction by modulating M1/M2 polarization of gut macrophages, whose underlying mechanism may be restoring gut microbiome and SCFA to restrain NLRP3 inflammasome activation.}, }
@article {pmid37961950, year = {2023}, author = {Guo, S and Shi, Y and Xu, A and Wang, Y and Xu, P}, title = {Liubao tea extract ameliorates ovalbumin-induced allergic asthma by regulating gut microbiota in mice.}, journal = {Food &amp; function}, volume = {14}, number = {23}, pages = {10605-10616}, doi = {10.1039/d3fo03470d}, pmid = {37961950}, issn = {2042-650X}, mesh = {Animals ; Mice ; Ovalbumin/adverse effects ; *Gastrointestinal Microbiome ; *Asthma/metabolism ; Cytokines/metabolism ; Tea/metabolism ; Mice, Inbred BALB C ; Disease Models, Animal ; Lung ; Bronchoalveolar Lavage Fluid ; }, abstract = {Asthma, a chronic airway inflammatory disease, has a complicated pathogenesis and limited therapeutic treatment. Evidence shows that the intestinal microbiota exhibits crucial functional interaction with asthma syndrome. Liubao tea (LBT), a type of postfermented tea in China, positively modulates gut microbiota. However, the potential benefits of LBT extract (LBTE) for allergic asthma are still not understood. Herein, the anti-inflammatory effects of LBTE and its modulation of the gut microbiota of asthmatic mice induced by ovalbumin were explored. The results demonstrate that LBTE significantly inhibited airway hyper-responsiveness and restrained the proliferation of proinflammatory cytokines and inflammatory cells associated with allergic asthma. Additionally, LBTE suppressed inflammatory infiltration, mucus secretion, and excessive goblet cell production by downregulating the gene expression of inflammatory indicators. Interestingly, fecal microbiota transplantation results further implied that the modulation of LBTE on gut microbiota played an essential role in alleviating airway inflammatory symptoms of allergic asthma.}, }
@article {pmid37961091, year = {2023}, author = {Dubey, H and Roychoudhury, R and Alex, A and Best, C and Liu, S and White, A and Carlson, A and Azcarate-Peril, MA and Mansfield, LS and Knickmeyer, R}, title = {Effect of Human Infant Gut Microbiota on Mouse Behavior, Dendritic Complexity, and Myelination.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.10.24.563309}, pmid = {37961091}, issn = {2692-8205}, abstract = {UNLABELLED: The mammalian gut microbiome influences numerous developmental processes. In human infants it has been linked with cognition, social skills, hormonal responses to stress, and brain connectivity. Yet, these associations are not necessarily causal. The present study tested whether two microbial stool communities, common in human infants, affected behavior, myelination, dendritic morphology, and spine density when used to colonize mouse models. Humanized animals were more like specific-pathogen free mice than germ-free mice for most phenotypes, although in males, both humanized groups were less social. Both humanized groups had thinner myelin sheaths in the hippocampus, than did germ-free animals. Humanized animals were similar to each other except for dendritic morphology and spine density where one group had greater dendritic length in the prefrontal cortex, greater dendritic volume in the nucleus accumbens, and greater spine density in both regions, compared to the other. Results add to a body of literature suggesting the gut microbiome impacts brain development.<br><br>TEASER: Fecal transplants from human infants with highly abundant Bifidobacterium , an important inhabitant of the intestinal tract of breastfed newborns, may promote brain connectivity in mice.}, }
@article {pmid37960284, year = {2023}, author = {Zheng, Y and Bonfili, L and Wei, T and Eleuteri, AM}, title = {Understanding the Gut-Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders.}, journal = {Nutrients}, volume = {15}, number = {21}, pages = {}, pmid = {37960284}, issn = {2072-6643}, support = {Fondi Studenti PhD//University of Camerino/ ; }, mesh = {Humans ; Brain-Gut Axis ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; *Alzheimer Disease/therapy ; *Parkinson Disease/therapy ; Brain ; Dysbiosis/therapy ; }, abstract = {The gut-brain axis (GBA) is a complex bidirectional communication network connecting the gut and brain. It involves neural, immune, and endocrine communication pathways between the gastrointestinal (GI) tract and the central nervous system (CNS). Perturbations of the GBA have been reported in many neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), among others, suggesting a possible role in disease pathogenesis. The gut microbiota is a pivotal component of the GBA, and alterations in its composition, known as gut dysbiosis, have been associated with GBA dysfunction and neurodegeneration. The gut microbiota might influence the homeostasis of the CNS by modulating the immune system and, more directly, regulating the production of molecules and metabolites that influence the nervous and endocrine systems, making it a potential therapeutic target. Preclinical trials manipulating microbial composition through dietary intervention, probiotic and prebiotic supplementation, and fecal microbial transplantation (FMT) have provided promising outcomes. However, its clear mechanism is not well understood, and the results are not always consistent. Here, we provide an overview of the major components and communication pathways of the GBA, as well as therapeutic approaches targeting the GBA to ameliorate NDDs.}, }
@article {pmid37958637, year = {2023}, author = {Han, Z and Min, Y and Pang, K and Wu, D}, title = {Therapeutic Approach Targeting Gut Microbiome in Gastrointestinal Infectious Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {21}, pages = {}, pmid = {37958637}, issn = {1422-0067}, support = {2022-I2M-1-003//CAMS Innovation Fund for Medical Sciences/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; *Gastrointestinal Diseases/therapy ; Diarrhea ; Salmonella typhimurium ; }, abstract = {While emerging evidence highlights the significance of gut microbiome in gastrointestinal infectious diseases, treatments like Fecal Microbiota Transplantation (FMT) and probiotics are gaining popularity, especially for diarrhea patients. However, the specific role of the gut microbiome in different gastrointestinal infectious diseases remains uncertain. There is no consensus on whether gut modulation therapy is universally effective for all such infections. In this comprehensive review, we examine recent developments of the gut microbiome's involvement in several gastrointestinal infectious diseases, including infection of Helicobacter pylori, Clostridium difficile, Vibrio cholerae, enteric viruses, Salmonella enterica serovar Typhimurium, Pseudomonas aeruginosa Staphylococcus aureus, Candida albicans, and Giardia duodenalis. We have also incorporated information about fungi and engineered bacteria in gastrointestinal infectious diseases, aiming for a more comprehensive overview of the role of the gut microbiome. This review will provide insights into the pathogenic mechanisms of the gut microbiome while exploring the microbiome's potential in the prevention, diagnosis, prediction, and treatment of gastrointestinal infections.}, }
@article {pmid37957893, year = {2023}, author = {Garner, W and Hamza, A and Haidar, G}, title = {Investigational non-antibiotic therapeutics for infections in hematopoietic cell transplant recipients and patients with hematologic malignancies receiving cellular therapies.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {25 Suppl 1}, number = {}, pages = {e14193}, doi = {10.1111/tid.14193}, pmid = {37957893}, issn = {1399-3062}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Transplant Recipients ; Bone Marrow Transplantation ; *Hematologic Neoplasms/complications/therapy ; Bone Marrow ; Granulocyte Colony-Stimulating Factor/pharmacology/therapeutic use ; }, abstract = {In the age of progressive antimicrobial resistance and increased difficulty combating infections in immunocompromised hosts, there has been renewed interest in the use of nontraditional therapeutics for infections. Herein, we review the use of investigational non-pharmaceutical anti-infective agents targeting fungal, bacterial, and viral infections in patients with hematologic malignancies, focusing on those receiving hematopoietic cell transplantation or cellular therapies. We discuss immune checkpoint inhibitors, granulocyte transfusions, bone marrow colony-stimulating factors, bacteriophages, fecal microbiota transplantation, and virus specific T-cell therapy. Although there is promising early experience with many of these treatments, further studies will be required to define their optimal role in the therapeutic armamentarium against infections in immunocompromised hosts.}, }
@article {pmid37956701, year = {2024}, author = {Bornbusch, SL and Power, ML and Schulkin, J and Drea, CM and Maslanka, MT and Muletz-Wolz, CR}, title = {Integrating microbiome science and evolutionary medicine into animal health and conservation.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {99}, number = {2}, pages = {458-477}, doi = {10.1111/brv.13030}, pmid = {37956701}, issn = {1469-185X}, support = {BCS 1749465//National Science Foundation/ ; IOS 2131060//National Science Foundation/ ; U4DMC39438//Pregnancy-Related Care Research Network (HRSA; HHS)/ ; //Smithsonian George E. Burch Fellowship in Theoretical Medicine and Affiliated Theoretical Science/ ; }, mesh = {Animals ; Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Ecology ; Mammals ; Diet ; }, abstract = {Microbiome science has provided groundbreaking insights into human and animal health. Similarly, evolutionary medicine - the incorporation of eco-evolutionary concepts into primarily human medical theory and practice - is increasingly recognised for its novel perspectives on modern diseases. Studies of host-microbe relationships have been expanded beyond humans to include a wide range of animal taxa, adding new facets to our understanding of animal ecology, evolution, behaviour, and health. In this review, we propose that a broader application of evolutionary medicine, combined with microbiome science, can provide valuable and innovative perspectives on animal care and conservation. First, we draw on classic ecological principles, such as alternative stable states, to propose an eco-evolutionary framework for understanding variation in animal microbiomes and their role in animal health and wellbeing. With a focus on mammalian gut microbiomes, we apply this framework to populations of animals under human care, with particular relevance to the many animal species that suffer diseases linked to gut microbial dysfunction (e.g. gut distress and infection, autoimmune disorders, obesity). We discuss diet and microbial landscapes (i.e. the microbes in the animal's external environment), as two factors that are (i) proposed to represent evolutionary mismatches for captive animals, (ii) linked to gut microbiome structure and function, and (iii) potentially best understood from an evolutionary medicine perspective. Keeping within our evolutionary framework, we highlight the potential benefits - and pitfalls - of modern microbial therapies, such as pre- and probiotics, faecal microbiota transplants, and microbial rewilding. We discuss the limited, yet growing, empirical evidence for the use of microbial therapies to modulate animal gut microbiomes beneficially. Interspersed throughout, we propose 12 actionable steps, grounded in evolutionary medicine, that can be applied to practical animal care and management. We encourage that these actionable steps be paired with integration of eco-evolutionary perspectives into our definitions of appropriate animal care standards. The evolutionary perspectives proposed herein may be best appreciated when applied to the broad diversity of species under human care, rather than when solely focused on humans. We urge animal care professionals, veterinarians, nutritionists, scientists, and others to collaborate on these efforts, allowing for simultaneous care of animal patients and the generation of valuable empirical data.}, }
@article {pmid37955340, year = {2023}, author = {Bibbò, S and Porcari, S and Del Vecchio, LE and Severino, A and Mullish, BH and Ianiro, G and Gasbarrini, A and Cammarota, G}, title = {Gut microbiota and immunotherapy of renal cell carcinoma.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {19}, number = {3}, pages = {2268982}, pmid = {37955340}, issn = {2164-554X}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *Carcinoma, Renal Cell/therapy ; *Gastrointestinal Microbiome ; Immunotherapy ; *Kidney Neoplasms/therapy ; Immune Checkpoint Inhibitors/therapeutic use ; *Neoplasms ; }, abstract = {The gut microbiome has recently been proposed as a key player in cancer development and progression. Several studies have reported that the composition of the gut microbiome plays a role in the response to immune checkpoint inhibitors (ICIs). The gut microbiome modulation has been investigated as a potential therapeutic strategy for cancer, mainly in patients undergoing therapy with ICIs. In particular, modulation through probiotics, FMT or other microbiome-related approaches have proven effective to improve the response to ICIs. In this review, we examine the role of the gut microbiome in enhancing clinical responses to ICIs in the treatment of renal cancer.}, }
@article {pmid37954280, year = {2023}, author = {Vasudevan, D and Ramakrishnan, A and Velmurugan, G}, title = {Exploring the diversity of blood microbiome during liver diseases: Unveiling Novel diagnostic and therapeutic Avenues.}, journal = {Heliyon}, volume = {9}, number = {11}, pages = {e21662}, pmid = {37954280}, issn = {2405-8440}, abstract = {Liver diseases are a group of major metabolic and immune or inflammation related diseases caused due to various reasons including infection, abnormalities in immune system, genetic defects, and lifestyle habits. However, the cause-effect relationship is not completely understood in liver disease. The role of microbiome, particularly, the role of gut and oral microbiome in liver diseases has been extensively studied in recent years. More interestingly, the presence of blood microbiome and tissue microbiome has been identified in many liver diseases. The translocation of microbes from the gut into the portal circulation has been attributed to be the major reason for the presence of blood microbial components and its clinical implications in liver disorders. Besides microbial translocation, Pathogen associated Molecular Patterns (PAMPs) derived from gut microbiota might also translocate. The presence of blood microbiome in liver disease has been reviewed earlier. However, the role of blood microbiome as a biomarker and therapeutic target in liver diseases has not been analysed earlier. In this review, we confabulate the origin and physiology of blood microbiome and blood microbial components in relation to the progression and pathogenesis of liver disease. In conclusion, we discuss the translational perspectives targeting the blood microbial components in the diagnosis and therapy of liver disease.}, }
@article {pmid37953693, year = {2024}, author = {Lee, RB and Gasparetto, M}, title = {Novel pharmacological developments in the management of paediatric inflammatory bowel disease: Time for guideline update - A narrative review.}, journal = {Journal of paediatrics and child health}, volume = {60}, number = {6}, pages = {168-175}, doi = {10.1111/jpc.16519}, pmid = {37953693}, issn = {1440-1754}, mesh = {Humans ; Child ; *Inflammatory Bowel Diseases/drug therapy ; Practice Guidelines as Topic ; }, abstract = {AIM: The incidence of paediatric inflammatory bowel disease (IBD) continues to increase in both adults and children across the globe, with more than one third of the patients not responding to anti-tumour necrosis factor biologics and immune modulators. This narrative review provides an overview of novel pharmacological developments in the management of paediatric IBD, including new biological therapies.<br><br>METHODS: A PubMed Medline search was performed to include randomised controlled trials, retrospective and prospective observational studies, and relevant case reports of children with IBD published between 2018 and January 2023. Guidelines and protocols from relevant paediatric and adult gastroenterology societies, such as the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organisation, were also included. Non-pharmacological treatments including therapeutic diets and faecal microbiota transplantation were outside the scope of this work.<br><br>RESULTS: Early real-world evidence suggests that newer biologics and small molecules, such as anti-integrins, interleukin-12 and/or interleukin-23 inhibitors, Janus kinase and signal transducer and activator of transcription proteins inhibitors, are safe and effective in adult patients with IBD, with promising growing evidence for paediatric IBD.<br><br>CONCLUSION: While many developments have been achieved with novel pharmacological treatments to manage IBD, ongoing research is required to confirm their effectiveness and safety in the paediatric age. Extending the licence of novel treatments to children will be crucial to tackle the increasing loss of response to conventional treatments. International guidelines will require timely updating to incorporate novel treatments within the existing protocols.}, }
@article {pmid37951913, year = {2023}, author = {Mousavinasab, F and Karimi, R and Taheri, S and Ahmadvand, F and Sanaaee, S and Najafi, S and Halvaii, MS and Haghgoo, A and Zamany, M and Majidpoor, J and Khosravifar, M and Baniasadi, M and Talebi, M and Movafagh, A and Aghaei-Zarch, SM and Khorram, N and Farnia, P and Kalhor, K}, title = {Microbiome modulation in inflammatory diseases: Progress to microbiome genetic engineering.}, journal = {Cancer cell international}, volume = {23}, number = {1}, pages = {271}, pmid = {37951913}, issn = {1475-2867}, abstract = {Recent developments in sequencing technology and analytical approaches have allowed researchers to show that the healthy gut microbiome is very varied and capable of performing a wide range of tasks. The importance of gut microbiota in controlling immunological, neurological, and endocrine function is becoming well-recognized. Thereby, numerous inflammatory diseases, including those that impact the gastrointestinal system, as well as less obvious ones, including Rheumatoid arthritis (RA), cancer, gestational diabetes (GD), type 1 diabetes (T1D), and type 2 diabetes (T2D), have been linked to dysbiotic gut microbiota. Microbiome engineering is a rapidly evolving frontier for solutions to improve human health. Microbiome engineering seeks to improve the function of an ecosystem by manipulating the composition of microbes. Thereby, generating potential therapies against metabolic, inflammatory, and immunological diseases will be possible through microbiome engineering. This essay first provides an overview of the traditional technological instruments that might be used for microbiome engineering, such as Fecal Microbiota Transplantation (FMT), prebiotics, and probiotics. Moreover, we will also discuss experimental genetic methods such as Metagenomic Alteration of Gut microbiome by In situ Conjugation (MAGIC), Bacteriophage, and Conjugative plasmids in manipulating intestinal microbiota.}, }
@article {pmid37950332, year = {2023}, author = {Promsuwan, O and Malathum, K and Ingsathit, A}, title = {Epidemiology of extended-spectrum β-lactamase-producing Enterobacterales infection in kidney transplant recipients.}, journal = {Antimicrobial resistance and infection control}, volume = {12}, number = {1}, pages = {123}, pmid = {37950332}, issn = {2047-2994}, mesh = {Humans ; Escherichia coli ; Prospective Studies ; *Kidney Transplantation/adverse effects ; beta-Lactamases ; *Bacteremia/epidemiology ; }, abstract = {BACKGROUND: Extended-spectrum b-lactamase (ESBL)-producing gram-negative bacilli (ESBL-GNB) are the most important pathogenic bacteria infecting kidney transplant patients. Kidney transplantation has been shown to be a risk factor for nosocomial ESBL-GNB bacteremia. The aims of this study were to describe the epidemiology of ESBL-GNB acquisition and to identify factors associated with ESBL-GNB infection in kidney transplant recipients, including pretransplant ESBL-GNB fecal carriage.<br><br>METHODS: A prospective study of patients undergoing kidney transplantation at Ramathibodi Hospital from March 1, 2019-November 30, 2020 was conducted. During this period, 66 patients who underwent kidney transplantation. Perianal swab cultures and urine cultures for ESBL-GNB were obtained from all subjects upon admission for transplantation and on Days 3, 7, 14 and 21 after surgery to determine the prevalence, incidence, and duration of admission before acquisition of the organisms.<br><br>RESULTS: Of the 66 patients undergoing kidney transplantation, 18 preoperative perianal swabs were detected to be positive for ESBL-GNB upon admission, representing 27.3% of the cases. The in-hospital perianal swab tests showed a significant increase to 96.8% positive ESBL-GNB cultures at the end of week 3. Approximately one-fourth (27.8%) of patients who acquired ESBL-GNB developed a postoperative symptomatic infection. The infection occurred in 13% of such patients who were not ESBL positive at first. These infections included urinary tract infections (20 cases, [30%], of which 55% were due to ESBL-GNB) and bloodstream infections (13 cases; of which 9 [69.2%] were due to ESBL-GNB). E. coli was the most common pathogen. Previous exposure to antibiotics, including surgical prophylaxis, underlying disease, duration of indwelling urinary catheters and ureteric stents, as well as other operative factors were not found to be significantly associated with the acquisition of ESBL-producing organisms in this dataset.<br><br>CONCLUSIONS: ESBL carriage may be a risk factor for the development of bacteremia and other serious infections among kidney transplant recipients, although a statistically significant difference could not be demonstrated owing to the small size of the sample. The high rate of ESBL acquisition suggests that more stringent infection prevention and control efforts are needed.}, }
@article {pmid37948152, year = {2023}, author = {Song, W and Wang, Y and Li, G and Xue, S and Zhang, G and Dang, Y and Wang, H}, title = {Modulating the gut microbiota is involved in the effect of low-molecular-weight Glycyrrhiza polysaccharide on immune function.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2276814}, pmid = {37948152}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Molecular Weight ; Polysaccharides/pharmacology ; *Glycyrrhiza ; Immunity ; }, abstract = {Low molecular weight (6.5 kDa) Glycyrrhiza polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut microbiota remains unclear. In this study, we aimed to reveal the mechanisms underlying GP-mediated regulation of immunity and gut microbiota using cyclophosphamide (CTX)-induced immunosuppressed and intestinal mucosal injury models. GP reversed CTX-induced intestinal structural damage and increased the number of goblet cells, CD4[+], CD8[+] T lymphocytes, and mucin content, particularly by maintaining the balance of helper T lymphocyte 1/helper T lymphocyte 2 (Th1/Th2). Moreover, GP alleviated immunosuppression by down-regulating extracellular regulated protein kinases/p38/nuclear factor kappa-Bp50 pathways and increasing short-chain fatty acids level and secretion of cytokines, including interferon-γ, interleukin (IL)-4, IL-2, IL-10, IL-22, and transforming growth factor-β3 and immunoglobulin (Ig) M, IgG and secretory immunoglobulin A. GP treatment increased the total species and diversity of the gut microbiota. Microbiota analysis showed that GP promoted the proliferation of beneficial bacteria, including Muribaculaceae_unclassified, Alistipes, Lachnospiraceae_NK4A136_group, Ligilactobacillus, and Clostridia_vadinBB60_group, and reduced the abundance of Proteobacteria and CTX-derived bacteria (Clostridiales_unclassified, Candidatus_Arthromitus, Firmicutes_unclassified, and Clostridium). The studies of fecal microbiota transplantation and the pseudo-aseptic model conformed that the gut microbiota is crucial in GP-mediated immunity regulation. GP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.}, }
@article {pmid37947218, year = {2024}, author = {Gudi, RR and Johnson, BM and Gaudreau, MC and Sun, W and Ball, L and Vasu, C}, title = {Intestinal permeability and inflammatory features of juvenile age correlate with the eventual systemic autoimmunity in lupus-prone female SWR × NZB F1 (SNF1) mice.}, journal = {Immunology}, volume = {171}, number = {2}, pages = {235-249}, pmid = {37947218}, issn = {1365-2567}, support = {P30 DK034987/DK/NIDDK NIH HHS/United States ; R01 DK136094/DK/NIDDK NIH HHS/United States ; R01DK136094/NH/NIH HHS/United States ; R21AI136339/NH/NIH HHS/United States ; R01AI138511/NH/NIH HHS/United States ; R01 AI138511/AI/NIAID NIH HHS/United States ; R21 AI136339/AI/NIAID NIH HHS/United States ; }, mesh = {Female ; Humans ; Male ; Mice ; Animals ; *Autoimmunity ; Intestinal Barrier Function ; Sexism ; *Lupus Erythematosus, Systemic ; Mice, Inbred NZB ; Autoantibodies ; Disease Models, Animal ; }, abstract = {The incidence of systemic lupus erythematosus (SLE) is about nine times higher in women than in men, and the underlying mechanisms that contribute to this gender bias are not fully understood. Previously, using lupus-prone (SWR × NZB)F1 (SNF1) mice, we have shown that the intestinal immune system could play a role in the initiation and progression of disease in SLE, and depletion of gut microbiota produces more pronounced disease protection in females than in males. Here, we show that the gut permeability features of lupus-prone female SNF1 mice at juvenile ages directly correlate with the expression levels of pro-inflammatory factors, faecal IgA abundance and nAg reactivity and the eventual systemic autoantibody levels and proteinuria onset. Furthermore, we observed that the disease protection achieved in female SNF1 mice upon depletion of gut microbiota correlates with the diminished gut inflammatory protein levels, intestinal permeability and circulating microbial DNA levels. However, faecal microbiota transplant from juvenile male and females did not result in modulation of gut inflammatory features or permeability. Overall, these observations suggest that the early onset of intestinal inflammation, systemic autoantibody production and clinical stage disease in lupus-prone females is linked to higher gut permeability in them starting at as early as juvenile age. While the higher gut permeability in juvenile lupus-prone females is dependent on the presence of gut microbes, it appears to be independent of the composition of gut microbiota.}, }
@article {pmid37944820, year = {2024}, author = {Zeng, K and Brewster, R and Kang, JB and Tkachenko, E and Brooks, E and Bhatt, AS and Fodor, AA and Andermann, TM}, title = {Acute Steroid-Refractory Gastrointestinal Graft-Versus-Host Disease Is Not Associated With Significant Differences in Gut Taxonomic Composition Compared to Steroid-Sensitive Gastrointestinal Graft-Versus-Host Disease Immediately Before Onset of Disease.}, journal = {Transplantation and cellular therapy}, volume = {30}, number = {2}, pages = {237.e1-237.e9}, pmid = {37944820}, issn = {2666-6367}, support = {K08 CA184420/CA/NCI NIH HHS/United States ; K23 AI163365/AI/NIAID NIH HHS/United States ; T32 GM144273/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Retrospective Studies ; *Gastrointestinal Tract ; *Graft vs Host Disease/therapy ; Leukocyte L1 Antigen Complex ; Steroids/therapeutic use ; }, abstract = {Taxonomic composition of the gut microbiota at the time of neutrophil engraftment is associated with the development of acute gastrointestinal graft-versus-host disease (GI GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation. However, less is known about the relationship between the gut microbiota and development of steroid-refractory GI GVHD immediately before the onset of disease. Markers of steroid-refractory GI GVHD are needed to identify patients who may benefit from the early initiation of non-corticosteroid-based GVHD treatment. Our aim was to identify differences in taxonomic composition in stool samples from patients without GVHD, with steroid-responsive GVHD and with steroid-refractory GI GVHD to identify predictive microbiome biomarkers of steroid-refractory GI GVHD. We conducted a retrospective case-control, single institution study, performing shotgun metagenomic sequencing on stool samples from patients with (n = 36) and without GVHD (n = 34) matched for time since transplantation. We compared the taxonomic composition of the gut microbiome in those with steroid-sensitive GI GVHD (n = 17) and steroid-refractory GI GVHD (n = 19) to each other and to those without GVHD. We also performed associations between steroid-refractory GI GVHD, gut taxonomic composition, and fecal calprotectin, a marker of GI GVHD to develop composite fecal markers of steroid-refractory GVHD before the onset of GI disease. We found that fecal samples within 30 days of GVHD onset from patients with and without GVHD or with and without steroid-refractory GI GVHD did not differ significantly in Shannon diversity (alpha-diversity) or in overall taxonomic composition (beta-diversity). Although those patients without GVHD had higher relative abundance of Clostridium spp., those with and without steroid-refractory GI GVHD did not significantly differ in taxonomic composition between one another. In our study, fecal calprotectin before disease onset was significantly higher in patients with GVHD compared to those without GVHD and higher in patients with steroid-refractory GI GVHD compared to steroid-sensitive GI GVHD. No taxa were significantly associated with higher levels of calprotectin.}, }
@article {pmid37944641, year = {2023}, author = {D, T and Venkatesh, MP}, title = {Fecal microbiota transplantation: History, procedure and regulatory considerations.}, journal = {Presse medicale (Paris, France : 1983)}, volume = {52}, number = {4}, pages = {104204}, doi = {10.1016/j.lpm.2023.104204}, pmid = {37944641}, issn = {2213-0276}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; Feces ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy ; *Clostridium Infections/therapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a medical treatment which involves the transfer of feces from a healthy donor to a recipient to restore the balance of gut microbiota and improve clinical outcomes. FMT has gained recognition in recent years due to its effectiveness in treating recurrent Clostridioides difficile infections (rCDI) and other gastrointestinal disorders. Additionally, it has been studied as an intervention for some other conditions, like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). This review covers regulatory considerations related to FMT, including the current state of FMT regulation and the need for further research to fully understand the safety and efficacy of this treatment. For transplantation of fecal microbiota, the Food and Drug Administration (FDA) classifies the treatment as an investigational new drug (IND), which typically requires physicians and scientists to submit an IND application. Ethical issues surrounding FMT, including the necessity of informed consent from donors and recipients and the potential transmission of infectious agents, are also discussed. Overall, FMT has the potential to offer significant therapeutic benefits, but it also raises regulatory and ethical considerations that require careful consideration. Further research is necessary to fully comprehend risks and benefits of FMT and to develop guidelines for its use in clinical practice.}, }
@article {pmid37942659, year = {2024}, author = {Normington, C and Chilton, CH and Buckley, AM}, title = {Clostridioides difficile infections; new treatments and future perspectives.}, journal = {Current opinion in gastroenterology}, volume = {40}, number = {1}, pages = {7-13}, pmid = {37942659}, issn = {1531-7056}, mesh = {Humans ; *Clostridioides difficile ; Dysbiosis/therapy ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy ; Fidaxomicin/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {PURPOSE OF REVIEW: As a significant cause of global morbidity and mortality, Clostridioides difficile infections (CDIs) are listed by the Centres for Disease Control and prevention as one of the top 5 urgent threats in the USA. CDI occurs from gut microbiome dysbiosis, typically through antibiotic-mediated disruption; however, antibiotics are the treatment of choice, which can result in recurrent infections. Here, we highlight new treatments available and provide a perspective on different classes of future treatments.<br><br>RECENT FINDINGS: Due to the reduced risk of disease recurrence, the microbiome-sparing antibiotic Fidaxomicin has been recommended as the first-line treatment for C. difficile infection. Based on the success of faecal microbiota transplantations (FMT) in treating CDI recurrence, defined microbiome biotherapeutics offer a safer and more tightly controlled alterative as an adjunct to antibiotic therapy. Given the association between antibiotic-mediated dysbiosis of the intestinal microbiota and the recurrence of CDI, future prospective therapies aim to reduce the dependence on antibiotics for the treatment of CDI.<br><br>SUMMARY: With current first-in-line antibiotic therapy options associated with high levels of recurrent CDI, the availability of new generation targeted therapeutics can really impact treatment success. There are still unknowns about the long-term implications of these new CDI therapeutics, but efforts to expand the CDI treatment toolbox can offer multiple solutions for clinicians to treat this multifaceted infectious disease to reduce patient suffering.}, }
@article {pmid37942583, year = {2023}, author = {Wang, Q and Lin, H and Shen, C and Zhang, M and Wang, X and Yuan, M and Yuan, M and Jia, S and Cao, Z and Wu, C and Chen, B and Gao, A and Bi, Y and Ning, G and Wang, W and Wang, J and Liu, R}, title = {Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2274124}, pmid = {37942583}, issn = {1949-0984}, mesh = {Mice ; Animals ; *Glucagon-Like Peptide 1/metabolism ; *Gastrointestinal Microbiome ; Signal Transduction ; Receptors, G-Protein-Coupled/genetics/metabolism ; Bile Acids and Salts ; Ileum ; }, abstract = {The gut microbiota interacts with intestinal epithelial cells through microbial metabolites to regulate the release of gut hormones. We investigated whether the gut microbiota affects the postprandial glucagon-like peptide-1 (GLP-1) response using antibiotic-treated mice and germ-free mice. Gut microbiome depletion completely abolished postprandial GLP-1 response in the circulation and ileum in a lipid tolerance test. Microbiome depletion did not influence the GLP-1 secretory function of primary ileal cells in response to stimulators in vitro, but dramatically changed the postprandial dynamics of endogenous bile acids, particularly ω-muricholic acid (ωMCA) and hyocholic acid (HCA). The bile acid receptor Takeda G protein-coupled receptor 5 (TGR5) but not farnesoid X receptor (FXR), participated in the regulation of postprandial GLP-1 response in the circulation and ileum, and ωMCA or HCA stimulated GLP-1 secretion via TGR5. Finally, fecal microbiota transplantation or ωMCA and HCA supplementation restored postprandial GLP-1 response. In conclusion, gut microbiota is indispensable for maintaining the postprandial GLP-1 response specifically in the ileum, and bile acid (ωMCA and HCA)-TGR5 signaling is involved in this process. This study helps to understand the essential interplay between the gut microbiota and host in regulating postprandial GLP-1 response and opens the foundation for new therapeutic targets.}, }
@article {pmid37939900, year = {2024}, author = {Bu, X and Gao, Y and Pan, W and Liu, L and Wang, J and Yin, Z and Ping, B}, title = {Human Amniotic Membrane-Derived Mesenchymal Stem Cells Prevent Acute Graft-Versus-Host Disease in an Intestinal Microbiome-Dependent Manner.}, journal = {Transplantation and cellular therapy}, volume = {30}, number = {2}, pages = {189.e1-189.e13}, doi = {10.1016/j.jtct.2023.11.005}, pmid = {37939900}, issn = {2666-6367}, mesh = {Humans ; Mice ; Animals ; *Gastrointestinal Microbiome ; Amnion/metabolism/pathology ; RNA, Ribosomal, 16S/genetics/metabolism ; Immunologic Factors/metabolism ; *Graft vs Host Disease/prevention &amp; control ; *Mesenchymal Stem Cells/metabolism ; }, abstract = {Acute graft-versus-host disease (aGVHD) represents a fatal severe complication after allogeneic hematopoietic stem cell transplantation. As a promising cell therapeutic strategy of aGVHD, the mechanism of mesenchymal stem cells (MSC) to ameliorate aGVHD has not been fully clarified, especially in the field of intestinal homeostasis including the intestinal microbiome involved in the pathogenesis of aGVHD. The present study aimed to explore the effect of MSC on intestinal homeostasis including the intestinal barrier and intestinal microbiome and its metabolites, as well as the role of intestinal microbiome in the preventive process of hAMSCs ameliorating aGVHD. The preventive effects of human amniotic membrane-derived MSC (hAMSCs) was assessed in humanized aGVHD mouse models. Immunohistochemistry and RT-qPCR were used to evaluate intestinal barrier function. The 16S rRNA sequencing and targeted metabolomics assay were performed to observe the alternation of intestinal microbiome and the amounts of medium-chain fatty acids (MCFAs) and short-chain fatty acids (SCFAs), respectively. Flow cytometry was performed to analyze the frequencies of T immune cells. Through animal experiments, we found that hAMSCs had the potential to prevent aGVHD. HAMSCs could repair the damage of intestinal barrier structure and function, as well as improve the dysbiosis of intestinal microbiome induced by aGVHD, and meanwhile, upregulate the concentration of metabolites SCFAs, so as to reshape intestinal homeostasis. Gut microbiota depletion and fecal microbial transplantation confirmed the involvement of intestinal microbiome in the preventive process of hAMSCs on aGVHD. Our findings showed that hAMSCs prevented aGVHD in an intestinal microbiome-dependent manner, which might shed light on a new mechanism of hAMSCs inhibiting aGVHD and promote the development of new prophylaxis regimes for aGVHD prevention.}, }
@article {pmid37938097, year = {2023}, author = {León-Janampa, N and Caballero-Posadas, I and Barc, C and Darrouzain, F and Moreau, A and Guinoiseau, T and Gatault, P and Fleurot, I and Riou, M and Pinard, A and Pezant, J and Rossignol, C and Gaudy-Graffin, C and Brand, D and Marlet, J}, title = {A pig model of chronic hepatitis E displaying persistent viremia and a downregulation of innate immune responses in the liver.}, journal = {Hepatology communications}, volume = {7}, number = {11}, pages = {}, pmid = {37938097}, issn = {2471-254X}, mesh = {Humans ; Swine ; Animals ; *Hepatitis E ; Down-Regulation ; Viremia ; Tacrolimus ; Immunity, Innate/genetics ; }, abstract = {BACKGROUND: Hepatitis E virus (HEV) is a zoonotic virus transmitted by pig meat and responsible for chronic hepatitis E in immunocompromised patients. It has proved challenging to reproduce this disease in its natural reservoir. We therefore aimed to develop a pig model of chronic hepatitis E to improve the characterization of this disease.<br><br>METHODS: Ten pigs were treated with a tacrolimus-based regimen and intravenously inoculated with HEV. Tacrolimus trough concentration, HEV viremia, viral diversity, innate immune responses, liver histology, clinical disease and biochemical markers were monitored for 11 weeks post-infection (p.i.).<br><br>RESULTS: HEV viremia persisted for 11 weeks p.i. HEV RNA was detected in the liver, small intestine, and colon at necropsy. Histological analysis revealed liver inflammation and fibrosis. Several mutations selected in the HEV genome were associated with compartmentalization in the feces and intestinal tissues, consistent with the hypothesis of extrahepatic replication in the digestive tract. Antiviral responses were characterized by a downregulation of IFN pathways in the liver, despite an upregulation of RIG-I and ISGs in the blood and liver.<br><br>CONCLUSIONS: We developed a pig model of chronic hepatitis E that reproduced the major hallmarks of this disease. This model revealed a compartmentalization of HEV genomes in the digestive tract and a downregulation of innate immune responses in the liver. These original features highlight the relevance of our model for studies of the pathogenesis of chronic hepatitis E and for validating future treatments.}, }
@article {pmid37937304, year = {2023}, author = {Chen, Z and Guan, D and Wang, Z and Li, X and Dong, S and Huang, J and Zhou, W}, title = {Microbiota in cancer: molecular mechanisms and therapeutic interventions.}, journal = {MedComm}, volume = {4}, number = {6}, pages = {e417}, pmid = {37937304}, issn = {2688-2663}, abstract = {The diverse bacterial populations within the symbiotic microbiota play a pivotal role in both health and disease. Microbiota modulates critical aspects of tumor biology including cell proliferation, invasion, and metastasis. This regulation occurs through mechanisms like enhancing genomic damage, hindering gene repair, activating aberrant cell signaling pathways, influencing tumor cell metabolism, promoting revascularization, and remodeling the tumor immune microenvironment. These microbiota-mediated effects significantly impact overall survival and the recurrence of tumors after surgery by affecting the efficacy of chemoradiotherapy. Moreover, leveraging the microbiota for the development of biovectors, probiotics, prebiotics, and synbiotics, in addition to utilizing antibiotics, dietary adjustments, defensins, oncolytic virotherapy, and fecal microbiota transplantation, offers promising alternatives for cancer treatment. Nonetheless, due to the extensive and diverse nature of the microbiota, along with tumor heterogeneity, the molecular mechanisms underlying the role of microbiota in cancer remain a subject of intense debate. In this context, we refocus on various cancers, delving into the molecular signaling pathways associated with the microbiota and its derivatives, the reshaping of the tumor microenvironmental matrix, and the impact on tolerance to tumor treatments such as chemotherapy and radiotherapy. This exploration aims to shed light on novel perspectives and potential applications in the field.}, }
@article {pmid37937006, year = {2023}, author = {Secondo, D and Massaro, D and Verrienti, G and Perri, F and Biscaglia, G}, title = {Clostridioides difficile Infection in the Neurorehabilitation Setting: Importance of a Multidisciplinary Approach and Impact of the Fecal Microbiota Transplantation.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e46574}, pmid = {37937006}, issn = {2168-8184}, abstract = {Clostridioides difficile infection (CDI) is considered to be one of the most frequent causes of bacterial infectious diarrhea in nosocomial settings. The prolonged hospitalization in bed-ridden conditions and the frequent administration of antibiotic therapy are usually encountered among the risk factors for CDI. Therefore, it is not surprising that CDI rates among rehabilitation hospitals are higher in neurologic facilities. In the neurorehabilitation setting, CDIs, especially if they present with refractory or recurrent aspects, may interrupt the normal course of rehabilitation, influencing, subsequently, the neurological outcomes. CDI treatment depends on the severity of the disease and includes both conservative and surgical approaches, with the latter reserved for severe complicated CDI. Another emerging, highly effective therapeutic option is represented by fecal microbiota transplantation (FMT), which consists of the transfer of screened healthy donor stool to a recipient's gastrointestinal tract. In this paper, we report two cases of refractory CDI, affecting patients in the neurorehabilitation pathway; both cases were resolved through FMT. On the one hand, our cases provide more evidence of FMT efficacy in refractory CDIs; on the other hand, they emphasize the need for a multidisciplinary approach to grant the best care to CDI patients.}, }
@article {pmid37936686, year = {2023}, author = {Reynolds, HM and Bettini, ML}, title = {Early-life microbiota-immune homeostasis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1266876}, pmid = {37936686}, issn = {1664-3224}, support = {R01 AI136963/AI/NIAID NIH HHS/United States ; R01 AI173406/AI/NIAID NIH HHS/United States ; R01 DK114456/DK/NIDDK NIH HHS/United States ; T32 AI138945/AI/NIAID NIH HHS/United States ; }, mesh = {Infant, Newborn ; Humans ; *Probiotics/therapeutic use ; Dysbiosis ; *Microbiota ; *Gastrointestinal Microbiome ; Homeostasis ; }, abstract = {As the prevalence of allergy and autoimmune disease in industrialized societies continues to rise, improving our understanding of the mechanistic roles behind microbiota-immune homeostasis has become critical for informing therapeutic interventions in cases of dysbiosis. Of particular importance, are alterations to intestinal microbiota occurring within the critical neonatal window, during which the immune system is highly vulnerable to environmental exposures. This review will highlight recent literature concerning mechanisms of early-life microbiota-immune homeostasis as well as discuss the potential for therapeutics in restoring dysbiosis in early life.}, }
@article {pmid37936242, year = {2023}, author = {Pan, C and Zhang, H and Zhang, L and Chen, L and Xu, L and Xu, N and Liu, X and Meng, Q and Wang, X and Zhang, ZY}, title = {Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {248}, pmid = {37936242}, issn = {2049-2618}, mesh = {Animals ; Mice ; *Cognitive Dysfunction ; Dexamethasone/pharmacology/therapeutic use ; Dysbiosis/etiology ; *Gastrointestinal Microbiome/genetics ; Indoles/pharmacology ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Gut microbial dysbiosis is associated with neurological diseases; however, the mechanisms by which the microbiota regulates postoperative gastrointestinal and cognitive function are incompletely understood.<br><br>METHODS: Behavioral testing, MiSeq 16S rRNA gene sequencing, non-target metabolism, intestinal permeability detection, protein assays, and immunofluorescence staining were employed to discern the impacts of surgery on microbial profiles, intestinal barriers, serum metabolism, and the brain. Interventions in mice included fecal microbiota transplantation, the anti-inflammatory agent dexamethasone, Lactobacillus supplementation, indole propionic acid supplementation, and palmitic amide administration.<br><br>RESULTS: Surgery-induced cognitive impairment occurs predominantly in aged mice, and surgery-induced alterations in the microbiota composition profile exacerbate intestinal barrier disruption in aged mice. These adverse effects can be mitigated by transferring microbiota from young donors or by bolstering the intestinal barrier function using dexamethasone, Lactobacillus, or indole propionic acid. Moreover, microbiota composition profiles can be restored by transplanting feces from young mice to aged surgical mice, improving neuropathology and cognitive function, and these effects coincide with increased intestinal permeability. Metabolomic screening identified alterations in metabolites in mouse serum after surgery, especially the increase in palmitic amide. Palmitic amide levels in serum and brain can be decreased by transplanting feces from young mice to aged surgical mice. Oral palmitic amide exacerbates cognitive impairment and neuropathological changes in mice.<br><br>CONCLUSIONS: Gut microbial dysbiosis in mice after surgery is a key mechanism leading to cognition dysfunction, which disrupts the intestinal barrier and metabolic abnormalities, resulting in neuroinflammation and dendritic spine loss. Intestinal barrier damage and high level of palmitic amide in old mice may be the cause of high incidence of PND in the elderly. Preoperative microbiota regulation and intestinal barrier restoration may be of therapeutic benefit in preventing PND. Video Abstract.}, }
@article {pmid37935653, year = {2024}, author = {Pandey, H and Jain, D and Tang, DWT and Wong, SH and Lal, D}, title = {Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease.}, journal = {Intestinal research}, volume = {22}, number = {1}, pages = {15-43}, pmid = {37935653}, issn = {1598-9100}, support = {021337-00001//Nanyang Technological University/ ; //Wang Lee Wah Memorial Fund/ ; RG37/22//Ministry of Education - Singapore/ ; }, abstract = {Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.}, }
@article {pmid37935276, year = {2023}, author = {Ye, X and Sun, P and Lao, S and Wen, M and Zheng, R and Lin, Y and Gan, L and Fan, X and Wang, P and Li, Z and Yan, X and Zhao, L}, title = {Fgf21-Dubosiella axis mediates the protective effects of exercise against NAFLD development.}, journal = {Life sciences}, volume = {334}, number = {}, pages = {122231}, doi = {10.1016/j.lfs.2023.122231}, pmid = {37935276}, issn = {1879-0631}, mesh = {Male ; Animals ; Mice ; *Non-alcoholic Fatty Liver Disease/prevention &amp; control/pathology ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Exercise ; Lipids ; }, abstract = {AIM: To explore the mechanism of gut microbiota mediates protective effects of exercise against non-alcoholic fatty liver disease (NAFLD) development.<br><br>MAIN METHODS: The male C57BL/6 mice were fed with high fat food (HFD) or normal diet (CON) respectively, and the obese mice were randomly divided into sedentariness (HFD) and exercise groups (HFD&#xa0;+&#xa0;Exe). The total intervention period was 18&#xa0;weeks. Antibiotic treatment and fecal microbiota transplantation were applied to evaluate gut microbiota mediates the protective effects of exercise against NAFLD development. 16S rDNA profiling of gut microbiota and extracorporeal rehydration of Dubosiella newyorkensis were performed to identify the crucial role of Dubosiella in NAFLD improvement during exercise training. FGF21 knock-out mice were used to reveal the potential mechanism of exercise increased the abundance of Dubosiella. RT-PCR, Western blot, Histopathological examinations and Biochemical testing were performed to evaluate the lipid deposition and function in the liver.<br><br>KEY FINDINGS: Treadmill exercise significantly ameliorated hepatic function and mitigated lipid accumulation in NAFLD mice, and these hepatoprotective benefits were mostly mediated by the Dubosiella. In addition, the increased abundance of Dubosiella during exercise training was modulated by FGF21 specifically.<br><br>SIGNIFICANCE: In short, Dubosiella, chiefly regulated by FGF21 signaling during exercise training, has been discovered to govern the protective impacts of exercising counter to the development of NAFLD and exhibits a promising treatment target for NAFLD.}, }
@article {pmid37934614, year = {2023}, author = {Zhang, T and Gao, G and Kwok, LY and Sun, Z}, title = {Gut microbiome-targeted therapies for Alzheimer's disease.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2271613}, pmid = {37934614}, issn = {1949-0984}, mesh = {Humans ; *Alzheimer Disease/therapy ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; Prebiotics ; *Synbiotics ; Dysbiosis/therapy ; }, abstract = {The advent of high-throughput 'omics' technologies has improved our knowledge of gut microbiome in human health and disease, including Alzheimer's disease (AD), a neurodegenerative disorder. Frequent bidirectional communications and mutual regulation exist between the gastrointestinal tract and the central nervous system through the gut-brain axis. A large body of research has reported a close association between the gut microbiota and AD development, and restoring a healthy gut microbiota may curb or even improve AD symptoms and progression. Thus, modulation of the gut microbiota has become a novel paradigm for clinical management of AD, and emerging effort has focused on developing potential novel strategies for preventing and/or treating the disease. In this review, we provide an overview of the connection and causal relationship between gut dysbiosis and AD, the mechanisms of gut microbiota in driving AD progression, and the successes and challenges of implementing available gut microbiome-targeted therapies (including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation) in preventive and/or therapeutic preclinical and clinical intervention studies of AD. Finally, we discuss the future directions in this field.}, }
@article {pmid37934064, year = {2024}, author = {Cao, Y and Zhang, L and Xiong, F and Guo, X and Kan, X and Song, S and Liang, B and Liang, B and Yu, L and Zheng, C}, title = {Effect of probiotics and fecal microbiota transplantation in dirty rats with established primary liver cancer.}, journal = {Future microbiology}, volume = {19}, number = {}, pages = {117-129}, doi = {10.2217/fmb-2022-0234}, pmid = {37934064}, issn = {1746-0921}, mesh = {Rats ; Animals ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; Feces ; *Probiotics/pharmacology ; *Liver Neoplasms/therapy ; }, abstract = {Background: The modulating effects of probiotics and fecal microbiota transplantation (FMT) on gut flora and their direct antitumor effects remain unclear in dirty rats with established primary liver cancer. Materials &amp; methods: Probiotics (VSL#3), FMT or tap water were administrated to three groups. Fresh fecal samples were collected from all groups for 16S rRNA analysis. Liver cancer tissues were collected to evaluate the tumor response. Results: Significant modulation of β-diversity (p = 0.023) was observed after FMT. VSL#3 and FMT had no inhibitory effect on tumors, but the density of Treg cells decreased (p = 0.031) in the FMT group. Conclusion: FMT is a more attractive alternative to probiotics in dirty rats with liver cancer.}, }
@article {pmid37933950, year = {2023}, author = {Zhang, M and Mo, R and Wang, H and Liu, T and Zhang, G and Wu, Y}, title = {Grape seed proanthocyanidin improves intestinal inflammation in canine through regulating gut microbiota and bile acid compositions.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {37}, number = {12}, pages = {e23285}, doi = {10.1096/fj.202300819RR}, pmid = {37933950}, issn = {1530-6860}, mesh = {Dogs ; Animals ; *Gastrointestinal Microbiome ; Bile Acids and Salts ; *Inflammatory Bowel Diseases/microbiology ; Inflammation ; Polyphenols/pharmacology ; }, abstract = {Although certain progress has been made in treating canine inflammatory bowel disease (IBD), a large proportion of dogs have a poor prognosis and may develop resistance and side effects. Therefore, it is of great significance to prevent or alleviate canine IBD through nutritional intervention. Plant polyphenol can interact with intestinal bacteria and has important prospects in the intestinal health improvement. This study evaluated the effect of grape seed proanthocyanidin (GSP), a plant-derived natural polyphenol, on Labrador Retrievers with mild IBD. In Experiment 1 of this study, GSP alleviated persistent intestinal inflammation in canines by improving inflammatory indexes and reducing intestinal permeability. Moreover, GSP treatment increased the abundance of bacteria with potential anti-inflammatory properties and engaging bile acid metabolism, including Ruminococcaceae, Faecalibacterium, Ruminococcus_torques_group, and Lachnospiraceae_NK4A136_group. Notably, targeted metabolomic analysis identified elevated productions of fecal chenodeoxycholic acid and its microbial transformation product lithocholic acid, which might contribute to relieving canine intestinal inflammation. Further, in Experiment 2, fecal microbiota transplantation was used to determine whether gut microbiota is a potential mechanism for GSP efficacy. Dogs with mild IBD received the fecal microbiota from the group administered GSP and mirrored the improvement effects of GSP, which results verified that gut microbial alteration could be an underlying mechanism for GSP efficiency on canine IBD. Our findings highlight that the mechanism of the GSP function on canine IBD is mediated by altering gut microbial composition and improving bile acid metabolism. This study proposes a natural polyphenol-based dietary strategy for improving canine intestinal health.}, }
@article {pmid37932511, year = {2024}, author = {Blake, SJ and Wolf, Y and Boursi, B and Lynn, DJ}, title = {Role of the microbiota in response to and recovery from cancer therapy.}, journal = {Nature reviews. Immunology}, volume = {24}, number = {5}, pages = {308-325}, pmid = {37932511}, issn = {1474-1741}, mesh = {Humans ; *Neoplasms/immunology/therapy/microbiology ; *Tumor Microenvironment/immunology ; Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation ; Animals ; Microbiota/immunology ; Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {Our understanding of how the microbiota affects the balance between response to and failure of cancer treatment by modulating the tumour microenvironment and systemic immune system has advanced rapidly in recent years. Microbiota-targeting interventions in patients with cancer are an area of intensive investigation. Promisingly, phase I-II clinical trials have shown that interventions such as faecal microbiota transplantation can overcome resistance to immune checkpoint blockade in patients with melanoma, improve therapeutic outcomes in treatment-naive patients and reduce therapy-induced immunotoxicities. Here, we synthesize the evidence showing that the microbiota is an important determinant of both cancer treatment efficacy and treatment-induced acute and long-term toxicity, and we discuss the complex and inter-related mechanisms involved. We also assess the potential of microbiota-targeting interventions, including bacterial engineering and phage therapy, to optimize the response to and recovery from cancer therapy.}, }
@article {pmid37928687, year = {2023}, author = {Okamura, T and Hasegawa, Y and Hamaguchi, M and Sasano, R and Fukui, M}, title = {The role of chicken eggs in modulating sarcopenic obesity and gut microbiota in db/db mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1281217}, pmid = {37928687}, issn = {1664-302X}, abstract = {BACKGROUND: Sarcopenia obesity, in which loss of muscle mass and fat accumulation occur simultaneously, is the pathological basis of type 2 diabetes mellitus. The usefulness of chicken eggs in sarcopenia prevention has been reported in several previous studies. The purpose of this study was to determine the beneficial effects of chicken eggs in the prevention of sarcopenic obesity in db/db mice.<br><br>METHODS: We raised 8-week-old db/db male mice, a model of sarcopenia obesity, for 8&#x2009;weeks and fed them a diet mixed with dried whole eggs. The fecal microbiota transplant (FMT) group was treated with antibiotics for 2&#x2009;weeks, starting at 6&#x2009;weeks of age, followed by FMT twice a week until 16&#x2009;weeks of age.<br><br>RESULTS: Eggs administered to db/db mice showed increased grip strength (p&#x2009;=&#x2009;0.022) and muscle mass (p&#x2009;=&#x2009;0.013), decreased visceral fat mass (p&#x2009;=&#x2009;0.005), and significantly increased physical activity (p&#x2009;<&#x2009;0.001). The FMT group of egg-fed mice showed a significant improvement in glucose intolerance and sarcopenic obesity. Sequencing of gene expression in the small intestine showed that the gene expression of amino acid transporters such as Slc6a18, Slc6a19, and Slc38a6 was increased in egg-fed mice. 16S rRNA sequencing of the gut microbiota showed an increase in the genus Vampirovibrio in both the egg-fed and FMT groups compared to that in egg-fed mice.<br><br>CONCLUSION: The results of this study indicate that egg consumption not only increases the intake of amino acids and other nutrients but also alters the intestinal microbiota and increases amino acid absorption from the intestinal tract, suggesting that eggs might contribute to the ameliorative mechanism of sarcopenic obesity.}, }
@article {pmid37927130, year = {2023}, author = {Lee, J and Kim, EJ and Park, GS and Kim, J and Kim, TE and Lee, YJ and Park, J and Kang, J and Koo, JW and Choi, TY}, title = {Lactobacillus reuteri ATG-F4 Alleviates Chronic Stress-induced Anhedonia by Modulating the Prefrontal Serotonergic System.}, journal = {Experimental neurobiology}, volume = {32}, number = {5}, pages = {313-327}, pmid = {37927130}, issn = {1226-2560}, abstract = {Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD). Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.}, }
@article {pmid37922956, year = {2023}, author = {Pilonis, N}, title = {Positive fecal immunochemical test but negative colonoscopy: what's next?.}, journal = {Endoscopy}, volume = {55}, number = {12}, pages = {1070-1071}, doi = {10.1055/a-2182-6316}, pmid = {37922956}, issn = {1438-8812}, mesh = {Humans ; *Colonoscopy ; Mass Screening ; Occult Blood ; *Colorectal Neoplasms/diagnosis ; Early Detection of Cancer ; Feces ; }, }
@article {pmid37924444, year = {2024}, author = {Rubio-Mora, E and Carrascoso, GR and Rodríguez, JG}, title = {Sapovirus infection as another cause of persistent viral diarrhea: case series and review of the literature.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {43}, number = {1}, pages = {55-59}, pmid = {37924444}, issn = {1435-4373}, mesh = {Humans ; Child ; Infant ; *Sapovirus/genetics ; Retrospective Studies ; *Caliciviridae Infections/diagnosis ; *Gastroenteritis/diagnosis ; Diarrhea/diagnosis ; *Adenovirus Infections, Human ; *Enterovirus Infections ; Immunosuppressive Agents ; Feces ; }, abstract = {Human sapovirus (HuSaV) is a common cause of gastroenteritis worldwide and is responsible for approximately 4% of acute gastroenteritis episodes in Europe. As reported with norovirus, patients with immunocompromised states are at increased risk of developing HuSaV infection, which can lead to persistent diarrhea and chronic viral shedding in some individuals. Chronic infections are incompletely investigated in these patients, and, due to the lack of specific treatment for HuSaV infection, different clinical approaches were carried out in order to provide further evidence on clinical evolution of these patients with different treatments. In this retrospective study, we report five immunocompromised pediatric patients with recurrent diarrhea caused by HuSaV and long-term viral shedding. Stool samples were analyzed by real-time PCR and tested for enteropathogenic viruses and bacteria and protozoa. Among transplant recipients, reduction of immunosuppressant therapy led to clinical improvement and relief of symptoms, maintaining a balance between managing the infection and preventing graft rejection. Nitazoxanide for 14 days was only used in one of these patients, showing to be an effective therapy to achieve reduction in time to resolution of symptoms. Neither nitazoxanide nor modification of immunosuppressant therapy could avoid recurrences. Further investigations are needed to develop new approaches that can both clear the infection and avoid persistent diarrhea in these patients.}, }
@article {pmid37923839, year = {2024}, author = {Routy, B and Lenehan, JG and Miller, WH and Jamal, R and Messaoudene, M and Daisley, BA and Hes, C and Al, KF and Martinez-Gili, L and Punčochář, M and Ernst, S and Logan, D and Belanger, K and Esfahani, K and Richard, C and Ninkov, M and Piccinno, G and Armanini, F and Pinto, F and Krishnamoorthy, M and Figueredo, R and Thebault, P and Takis, P and Magrill, J and Ramsay, L and Derosa, L and Marchesi, JR and Parvathy, SN and Elkrief, A and Watson, IR and Lapointe, R and Segata, N and Haeryfar, SMM and Mullish, BH and Silverman, MS and Burton, JP and Maleki Vareki, S}, title = {Author Correction: Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial.}, journal = {Nature medicine}, volume = {30}, number = {2}, pages = {604}, doi = {10.1038/s41591-023-02650-8}, pmid = {37923839}, issn = {1546-170X}, }
@article {pmid37921501, year = {2023}, author = {Wang, H and Bi, H and Yang, M and Wang, X and Song, C and Yang, W and Wang, Y and Xie, D and Li, H and Zhou, Z}, title = {Intestinal flora altered and correlated with interleukin-2/4 in patients with primary immune thrombocytopenia.}, journal = {Hematology (Amsterdam, Netherlands)}, volume = {28}, number = {1}, pages = {2277501}, doi = {10.1080/16078454.2023.2277501}, pmid = {37921501}, issn = {1607-8454}, mesh = {Humans ; *Gastrointestinal Microbiome ; Interleukin-2 ; Interleukin-4 ; *Purpura, Thrombocytopenic, Idiopathic ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Little is known about the changes and mechanisms of intestinal flora in primary immune thrombocytopenia (ITP) patients.<br><br>AIM: To explore the structural and functional differences of intestinal flora between ITP patients and healthy controls, and clarify the correlation between intestinal flora and Th1/Th2 imbalance.<br><br>METHODS: Feces from ITP patients and healthy controls were studied by 16S rRNA and metagenomic techniques at phylum, genus, species or functional levels. Blood samples were collected for the detection of interleukin -2 (IL-2) and IL-4 concentrations.<br><br>RESULTS: The following changes in ITP patients were found: a decrease of Bacteroidetes phylum, an increase of Proteobacteria phylum and alterations of ten genera and 1045 species. IL-2 and IL-4 were significantly correlated with six and five genera, respectively. Species of C. freundii, C. rodentium, and C. youngae were negatively correlated with bleeding scores, and S. infantis was positively related to platelet counts. Functionally, the intestinal flora of ITP patients changed mainly in terms of motility, chemotaxis, membrane transport, and metabolism.<br><br>CONCLUSION: The mechanism underlying functional and structural changes of intestinal flora in ITP patients may be related to inflammation and immunity, providing possibilities of probiotics or fecal transplants for ITP.}, }
@article {pmid37918500, year = {2024}, author = {Feng, W and Zhang, Y and Zhang, Y and Dong, Y and Wu, J and Chen, Q and Liu, M and Wang, D and Wu, Y and Wang, T}, title = {Anemoside B4 ameliorates dextran sulfate sodium (DSS)-induced colitis through inhibiting NLRP3 inflammasome and modulating gut microbiota.}, journal = {European journal of pharmacology}, volume = {963}, number = {}, pages = {176164}, doi = {10.1016/j.ejphar.2023.176164}, pmid = {37918500}, issn = {1879-0712}, mesh = {Animals ; Mice ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; *Gastrointestinal Microbiome ; Dextran Sulfate/toxicity ; Dysbiosis ; *Colitis/chemically induced/drug therapy ; *Colitis, Ulcerative ; Colon ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Ulcerative colitis (UC) has been recognized as a chronic and relapsing inflammatory disease of the gastrointestinal tract. Clinically, aminosalicylates, immunosuppressants and biological agents are commonly used to treat UC at different stages of the disease. However, these drugs often have side effects. Here, we investigated the anti-UC activity of Anemoside B4 (AB4) in mice with dextran sulfate sodium (DSS) induced colitis. Colon tissues, serum, and colonic contents were collected for assessment of intestinal barrier function, inflammatory cytokines production and microenvironment of intestinal microbiota. Results showed that AB4 alleviated colon shortening, weight lossing and histopathological damage in DSS-induced mice. In addition, we demonstrated both in vivo and in vitro that AB4 remarkably ameliorated colonic inflammation through suppressing NLRP3 pathway. Moreover, AB4 strengthened the intestinal epithelial barrier by regulating myosin light chain kinase (MLCK)-phosphorylated myosin light chain 2 (pMLC2) signaling pathway. Furthermore, we performed 16 S rRNA gene sequencing and fecal microbiome transplantation (FMT) experiments to demonstrate that AB4 alleviated colitis through regulating dysbiosis of intestinal microbiota. These results revealed that AB4 effectively ameliorate experimental UC mainly through regulating MLCK/pMLC2 pathway, NLRP3 pathway and dysbiosis of microbiota, provided new insights into the development of novel anti-UC drugs.}, }
@article {pmid37918459, year = {2024}, author = {Ross, FC and Mayer, DE and Gupta, A and Gill, CIR and Del Rio, D and Cryan, JF and Lavelle, A and Ross, RP and Stanton, C and Mayer, EA}, title = {Existing and Future Strategies to Manipulate the Gut Microbiota With Diet as a Potential Adjuvant Treatment for Psychiatric Disorders.}, journal = {Biological psychiatry}, volume = {95}, number = {4}, pages = {348-360}, doi = {10.1016/j.biopsych.2023.10.018}, pmid = {37918459}, issn = {1873-2402}, support = {U54 DK123755/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Diet ; *Mental Disorders ; Brain ; *Brain Diseases/metabolism ; }, abstract = {Nutrition and diet quality play key roles in preventing and slowing cognitive decline and have been linked to multiple brain disorders. This review compiles available evidence from preclinical studies and clinical trials on the impact of nutrition and interventions regarding major psychiatric conditions and some neurological disorders. We emphasize the potential role of diet-related microbiome alterations in these effects and highlight commonalities between various brain disorders related to the microbiome. Despite numerous studies shedding light on these findings, there are still gaps in our understanding due to the limited availability of definitive human trial data firmly establishing a causal link between a specific diet and microbially mediated brain functions and symptoms. The positive impact of certain diets on the microbiome and cognitive function is frequently ascribed with the anti-inflammatory effects of certain microbial metabolites or a reduction of proinflammatory microbial products. We also critically review recent research on pro- and prebiotics and nondietary interventions, particularly fecal microbiota transplantation. The recent focus on diet in relation to brain disorders could lead to improved treatment outcomes with combined dietary, pharmacological, and behavioral interventions.}, }
@article {pmid37918425, year = {2023}, author = {Scharl, M and Rogler, G}, title = {[Microbiome: from pathophysiology to clinical application?].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {148}, number = {22}, pages = {1419-1424}, doi = {10.1055/a-1951-0063}, pmid = {37918425}, issn = {1439-4413}, mesh = {Humans ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Microbiota ; Treatment Outcome ; }, abstract = {The "microbiome" or the intestinal microbiota is currently in the focus of scientific interest. The number of publications on the topic of the microbiome is increasing every year. In particular, the role of the microbiome in the pathophysiology of various diseases has been studied. Currently it is impossible to have an overview on all new developments with over 25.000 publication in the field per year. However, some key news stand out from this large number of publications. The first microbiota compounds for the therapy of Clostridioides difficile colitis were approved by the FDA last year or are about to be approved. This means that, for the first time, standardized microbiome products are available in addition to fecal microbiota transplantation (FMT) and are finding their way into everyday clinical practice.}, }
@article {pmid37916626, year = {2024}, author = {Zhang, L and Ma, XG}, title = {A Comprehensive Review on Biotransformation, Interaction, and Health of Gut Microbiota and Bioactive Components.}, journal = {Combinatorial chemistry &amp; high throughput screening}, volume = {27}, number = {11}, pages = {1551-1565}, pmid = {37916626}, issn = {1875-5402}, support = {JYZY-2022-72//Key Project of Jiyuan Vocational and Technical College, China/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Biotransformation ; Animals ; Flavonoids/metabolism/pharmacology/chemistry ; }, abstract = {BACKGROUND: The relationship between gut microbiota and bioactive components has become the research focus in the world. We attempted to clarify the relationship between biotransformation and metabolites of gut microbiota and bioactive components, and explore the metabolic pathway and mechanism of bioactive ingredients in vivo, which will provide an important theoretical basis for the clinical research of bioactive ingredients and rationality of drugs, and also provide an important reference for the development of new drugs with high bioavailability.<br><br>METHODS: The related references of this review on microbiota and bioactive components were collected from both online and offline databases, such as ScienceDirect, PubMed, Elsevier, Willy, SciFinder, Google Scholar, Web of Science, Baidu Scholar, SciHub, Scopus, and CNKI.<br><br>RESULTS: This review summarized the biotransformation of bioactive components under the action of gut microbiota, including flavonoids, terpenoids, phenylpropanoids, alkaloids, steroids, and other compounds. The interaction of bioactive components and gut microbiota is a key link for drug efficacy. Relevant research is crucial to clarify bioactive components and their mechanisms, which involve the complex interaction among bioactive components, gut microbiota, and intestinal epithelial cells. This review also summarized the individualized, precise, and targeted intervention of gut microbiota in the field of intestinal microorganisms from the aspects of dietary fiber, microecological agents, fecal microbiota transplantation, and postbiotics. It will provide an important reference for intestinal microecology in the field of nutrition and health for people.<br><br>CONCLUSION: To sum up, the importance of human gut microbiota in the research of bioactive components metabolism and transformation has attracted the attention of scholars all over the world. It is believed that with the deepening of research, human gut microbiota will be more widely used in the pharmacodynamic basis, drug toxicity relationship, new drug discovery, drug absorption mechanism, and drug transport mechanism in the future.}, }
@article {pmid37915416, year = {2023}, author = {Zhang, D and Tang, Y and Bai, X and Li, D and Zhou, M and Yu, C and Wu, H}, title = {Efficacy and safety of fecal microbiota transplantation for the treatment of irritable bowel syndrome: an overview of overlapping systematic reviews.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1264779}, pmid = {37915416}, issn = {1663-9812}, abstract = {Aim: Evidence from overlapping systematic reviews (SRs) and meta-analyses (MAs) has yielded conflicting results on the treatment of irritable bowel syndrome (IBS) with fecal microbiota transplantation (FMT). To thoroughly gather, assess, and synthesize evidence on FMT for IBS, we carried out the present study. Methods: A comprehensive search was conducted in Cochrane Library, Web of Science, PubMed, and Embase from inception to May 2023. Tools for assessing the methodological quality, reporting quality, and confidence in outcomes, including A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Seven eligible SRs/MAs were finally included in this overview. By AMSTAR-2, the methodological quality of SRs/MAs included five that were very low quality, one that was low quality, and one that was high quality. According to PRISMA, limitations were associated with items 5 (Method: Protocol and Registration), 8 (Method: Search), and 27 (Funding). In GRADE, a total of 19 outcomes were included in the seven reviews, of which 12 outcomes were low quality and seven outcomes were moderate quality. Imprecision due to small sample size was the primary factor leading to evidence downgrading. Conclusion: We conclude that there is insufficient evidence to determine whether FMT has a more beneficial effect on patient with IBS than placebo treatment. Well-designed, larger trails are needed to provide evidence in this field. In addition, selection of donor, route of administration, dosage, and frequency still need to be determined.}, }
@article {pmid37915336, year = {2023}, author = {Carrington, AE and Maloh, J and Nong, Y and Agbai, ON and Bodemer, AA and Sivamani, RK}, title = {The Gut and Skin Microbiome in Alopecia: Associations and Interventions.}, journal = {The Journal of clinical and aesthetic dermatology}, volume = {16}, number = {10}, pages = {59-64}, pmid = {37915336}, issn = {1941-2789}, abstract = {OBJECTIVE: This review examines the current literature on the gut-skin connection in alopecia and summarizes interventions that impact hair growth by modulation of the gut or skin microbiome.<br><br>METHODS: PubMed searches were done to assess studies of the gut and skin microbiome and forms of alopecia including, alopecia areata (AA), androgenic alopecia (AGA), alopecia universalis (AU), central centrifugal cicatricial alopecia (CCCA) and lichen planopilaris (LPP). Filters were applied for human and animal studies. Articles not translated to English and studies assessing supplemental therapies on alopecia were excluded.<br><br>RESULTS: There is evidence that scalp, hair follicle, and gut microbiome alterations are associated with various types of alopecia. There is potential in the use of interventions targeting microbiome dysbiosis, including fecal transplants and probiotics.<br><br>LIMITATIONS: This field of study still requires more high-quality research and studies with larger participant populations.<br><br>CONCLUSION: Dysbiosis on the scalp, within the hair follicle and the gut seem to have a role in the pathophysiology of various forms of alopecia. There is evidence that interventions targeting dysbiosis may have potential in the treatment and management of hair loss. Further studies are needed to establish a direct connection and to clarify specific effects of these interventions.}, }
@article {pmid37914662, year = {2023}, author = {Yu, Y and Wang, W and Zhang, F}, title = {The Next Generation Fecal Microbiota Transplantation: To Transplant Bacteria or Virome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {10}, number = {35}, pages = {e2301097}, pmid = {37914662}, issn = {2198-3844}, support = {2021YFA0717004//National Key Research and Development Program of China/ ; //Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Virome ; Feces/microbiology ; Bacteria ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for dysbiosis-related diseases. However, the clinical practice of crude fecal transplants presents limitations in terms of acceptability and reproductivity. Consequently, two alternative solutions to FMT are developed: transplanting bacteria communities or virome. Advanced methods for transplanting bacteria mainly include washed microbiota transplantation and bacteria spores treatment. Transplanting the virome is also explored, with the development of fecal virome transplantation, which involves filtering the virome from feces. These approaches provide more palatable options for patients and healthcare providers while minimizing research heterogeneity. In general, the evolution of the next generation of FMT in global trends is fecal microbiota components transplantation which mainly focuses on transplanting bacteria or virome.}, }
@article {pmid37914097, year = {2024}, author = {He, H and He, H and Mo, L and You, Z and Zhang, J}, title = {Priming of microglia with dysfunctional gut microbiota impairs hippocampal neurogenesis and fosters stress vulnerability of mice.}, journal = {Brain, behavior, and immunity}, volume = {115}, number = {}, pages = {280-294}, doi = {10.1016/j.bbi.2023.10.031}, pmid = {37914097}, issn = {1090-2139}, mesh = {Humans ; Mice ; Male ; Animals ; *Depression/microbiology ; *Gastrointestinal Microbiome ; Microglia ; Minocycline/pharmacology ; RNA, Ribosomal, 16S ; Mice, Inbred C57BL ; Hippocampus ; Neurogenesis/physiology ; Stress, Psychological ; }, abstract = {BACKGROUND: Mental disorders may be involved in neuroinflammatory processes that are triggered by gut microbiota. How gut microbiota influence microglia-mediated sensitivity to stress remains unclear. Here we explored in an animal model of depression whether disruption of the gut microbiome primes hippocampal microglia, thereby impairing neurogenesis and sensitizing to stress.<br><br>METHODS: Male C57BL/6J mice were exposed to chronic unpredictable mild stress (CUMS) for 4&#xa0;weeks, and effects on gut microbiota were assessed using 16S rRNA sequencing. Fecal microbiota was transplanted from control or CUMS mice into na&#xef;ve animals. The depression-like behaviors of recipients were evaluated in a forced swimming test and sucrose preference test. The morphology and phenotype of microglia in the hippocampus of recipients were examined using immunohistochemistry, quantitative PCR, and enzyme-linked immunosorbent assays. The recipients were treated with lipopolysaccharide or chronic stress exposure, and effects were evaluated on behavior, microglial responses and hippocampal neurogenesis. Finally, we explored the ability of minocycline to reverse the effects of CUMS on hippocampal neurogenesis and stress sensitivity in recipients.<br><br>RESULTS: CUMS altered the gut microbiome, leading to higher relative abundance of some bacteria (Helicobacter, Bacteroides, and Desulfovibrio) and lower relative abundance of some bacteria (Lactobacillus, Bifidobacterium, and Akkermansia). Fecal microbiota transplantation from CUMS mice to na&#xef;ve animals induced microglial priming in the dentate gyrus of recipients. This microglia showed hyper-ramified morphology, and became more sensitive to LPS challenge or chronic stress, which characterized by more significant morphological changes and inflammatory responses, as well as impaired hippocampal neurogenesis and increased depressive-like behaviors. Giving minocycline to recipients reversed these effects of fecal transplantation.<br><br>CONCLUSIONS: These findings suggest that gut microbiota from stressed animals can induce microglial priming in the dentate gyrus, which is associated with a hyper-immune response to stress and impaired hippocampal neurogenesis. Remodeling the gut microbiome or inhibiting microglial priming may be strategies to reduce sensitivity to stress.}, }
@article {pmid37910603, year = {2023}, author = {Woodworth, MH and Conrad, RE and Haldopoulos, M and Pouch, SM and Babiker, A and Mehta, AK and Sitchenko, KL and Wang, CH and Strudwick, A and Ingersoll, JM and Philippe, C and Lohsen, S and Kocaman, K and Lindner, BG and Hatt, JK and Jones, RM and Miller, C and Neish, AS and Friedman-Moraco, R and Karadkhele, G and Liu, KH and Jones, DP and Mehta, CC and Ziegler, TR and Weiss, DS and Larsen, CP and Konstantinidis, KT and Kraft, CS}, title = {Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement.}, journal = {Science translational medicine}, volume = {15}, number = {720}, pages = {eabo2750}, pmid = {37910603}, issn = {1946-6242}, support = {P51 OD011132/OD/NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; S10 OD026799/OD/NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; P30 AI050409/AI/NIAID NIH HHS/United States ; K23 AI144036/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; Anti-Bacterial Agents/pharmacology ; *Gastrointestinal Microbiome ; Drug Resistance, Bacterial ; Feces/microbiology ; Treatment Outcome ; }, abstract = {Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa (Akkermansia muciniphila, Alistipes putredinis, Phocaeicola dorei, Phascolarctobacterium faecium, Alistipes species, Mesosutterella massiliensis, Barnesiella intestinihominis, and Faecalibacterium prausnitzii) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible Enterobacterales strains that replaced baseline extended-spectrum β-lactamase-producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.}, }
@article {pmid37909786, year = {2023}, author = {Richie, TG and Heeren, L and Kamke, A and Monk, K and Pogranichniy, S and Summers, T and Wiechman, H and Ran, Q and Sarkar, S and Plattner, BL and Lee, STM}, title = {Limitation of amino acid availability by bacterial populations during enhanced colitis in IBD mouse model.}, journal = {mSystems}, volume = {8}, number = {6}, pages = {e0070323}, pmid = {37909786}, issn = {2379-5077}, support = {P30 GM122731/GM/NIGMS NIH HHS/United States ; P20 GM103418/GM/NIGMS NIH HHS/United States ; U54 HD090216/HD/NICHD NIH HHS/United States ; S10 OD021743/OD/NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; }, mesh = {Mice ; Animals ; Amino Acids ; *Gastrointestinal Microbiome ; *Colitis/microbiology ; Inflammation ; *Inflammatory Bowel Diseases/drug therapy ; Bacteria ; }, abstract = {Inflammatory bowel disease is associated with an increase in Enterobacteriaceae and Enterococcus species; however, the specific mechanisms are unclear. Previous research has reported the associations between microbiota and inflammation, here we investigate potential pathways that specific bacteria populations use to drive gut inflammation. Richie et al. show that these bacterial populations utilize an alternate sulfur metabolism and are tolerant of host-derived immune-response products. These metabolic pathways drive host gut inflammation and fuel over colonization of these pathobionts in the dysbiotic colon. Cultured isolates from dysbiotic mice indicated faster growth supplemented with L-cysteine, showing these microbes can utilize essential host nutrients.}, }
@article {pmid37906091, year = {2023}, author = {Zhou, H and Yu, B and Sun, J and Chen, H and Liu, Z and Ge, L and Chen, D}, title = {Gut microbiota absence and transplantation affect diarrhea: an investigation in the germ-free piglet model.}, journal = {Animal biotechnology}, volume = {34}, number = {8}, pages = {3971-3977}, doi = {10.1080/10495398.2023.2248200}, pmid = {37906091}, issn = {1532-2378}, mesh = {Swine ; Animals ; Female ; *Gastrointestinal Microbiome ; Diarrhea/therapy/veterinary ; Fecal Microbiota Transplantation ; Feces ; }, abstract = {This experiment was conducted to explore the effects of gut microbiota on neonatal diarrhea in a germ-free (GF) pig model. Twelve hysterectomy-derived GF piglets were housed in six sterile isolators. Among them, six piglets were treated as the GF group, and the other six piglets were orally introduced with healthy sow fecal suspension and regarded as the fecal microbiota transplantation (FMT) group. Another six piglets from natural birth were considered as the conventional (CV) group. The GF and FMT piglets were hand-fed with sterile milk powder for 21 days, and the CV piglets were suckled for the same days. Then, all piglets were fed with sterile feed for another 21 days. Results exhibited that the GF group's fecal score and moisture level were higher than those in the CV and FMT groups (p < 0.05). Meanwhile, the abundances of colonic AQP1 and AQP8 in the GF group were the greatest among these treatments (p < 0.05). However, FMT piglets had a lower fecal score in d 22-28 and d 29-35 than that in the CV piglets (p < 0.05). Collectively, the absence of gut microbiota may cause diarrhea in the piglet model, and transplantation of maternal fecal microbiota may reverse it.}, }
@article {pmid37905694, year = {2024}, author = {Tian, X and Wang, G and Teng, F and Xue, X and Pan, J and Mao, Q and Guo, D and Song, X and Ma, K}, title = {Zhi Zi Chi decoction (Gardeniae fructus and semen Sojae Praeparatum) attenuates anxious depression via modulating microbiota-gut-brain axis in corticosterone combined with chronic restraint stress-induced mice.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {30}, number = {4}, pages = {e14519}, pmid = {37905694}, issn = {1755-5949}, support = {//National Natural Science Foundation of China/ ; //Natural Science Foundation of Shandong Province/ ; //Shandong Province Universities' Development Plan for Youth Innovation Teams/ ; }, mesh = {Mice ; Animals ; Depression/drug therapy/etiology ; *Gardenia/chemistry ; Corticosterone ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Brain-Gut Axis ; RNA, Ribosomal, 16S ; Seeds/chemistry ; Antidepressive Agents ; }, abstract = {BACKGROUND: The microbiota-gut-brain axis plays a critical role in neuropsychiatric disorders, particularly anxious depression, and attracts more attention gradually. Zhi Zi Chi decoction (ZZCD) consisting of Gardenia jasminoides J. Ellis and Glycine max (L.) Merr, is a classic formula in clinic and widely applied in anxiety and depression treatment. However, the underlying mechanisms of regulating microbiota-gut-brain axis in the treatment of anxious depression by oral administration of ZZCD remain elusive.<br><br>MATERIALS AND METHODS: In this project, we clarified the origin and preparation methods of the Gardenia jasminoides J. Ellis and Glycine max (L.) Merr and examined the chemical ingredients of ZZCD by liquid chromatograph mass spectrometer. Then, corticosterone combined with chronic restraint stress was applied to establish an anxious depression model. After treated with ZZCD standard decoction, based on enzyme-linked immunosorbent assay (ELISA), 16S rRNA technology, high-throughput sequencing, quantitative RT-PCR and fecal microbiota transplantation (FMT), the multiple associations between nucleus accumbens and intestinal flora in anxious depression mice were determined to clarify the mechanism of ZZCD in the treatment of anxiety and depression disorder.<br><br>RESULTS: We found various substances with antidepressant and antianxiety properties in ZZCD such as rosiridin and oleanolic acid. ZZCD could alleviate depressive and anxiety behaviors in anxious depression mice via regulating the disturbance of gut microbiota. Meanwhile, the bioactive compounds of ZZCD might directly active on neurodevelopment and neuroimmune-related genes. Furthermore, the secretion of prolactin and estrogen, and interfering with mitogen-activated protein kinase (MAPK) and tumor necrosis factor (TNF) signaling pathways were mainly involved in the multi-target therapeutic effects of ZZCD against anxiety and depression.<br><br>CONCLUSIONS: These findings suggested that ZZCD exerts antidepressant effects pleiotropically through modulating the microbiota-gut-brain.}, }
@article {pmid37902074, year = {2023}, author = {Balzano, T and Llansola, M and Arenas, YM and Izquierdo-Altarejos, P and Felipo, V}, title = {Hepatic encephalopathy: investigational drugs in preclinical and early phase development.}, journal = {Expert opinion on investigational drugs}, volume = {32}, number = {11}, pages = {1055-1069}, doi = {10.1080/13543784.2023.2277386}, pmid = {37902074}, issn = {1744-7658}, mesh = {Humans ; *Hepatic Encephalopathy/drug therapy ; Drugs, Investigational/pharmacology/therapeutic use ; Neuroinflammatory Diseases ; Ammonia/therapeutic use ; Inflammation ; }, abstract = {INTRODUCTION: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, in patients with liver disease, which affects life quality and span. Current treatments are lactulose or rifaximin, acting on gut microbiota. Treatments aiming ammonia levels reduction have been tested with little success.<br><br>AREAS COVERED: Pre-clinical research shows that the process inducing HE involves sequentially: liver failure, altered microbiome, hyperammonemia, peripheral inflammation, changes in immunophenotype and extracellular vesicles and neuroinflammation, which alters neurotransmission impairing cognitive and motor function. HE may be reversed using drugs acting at any step: modulating microbiota with probiotics or fecal transplantation; reducing peripheral inflammation with anti-TNF&#x3b1;, autotaxin inhibitors or silymarin; reducing neuroinflammation with sulforaphane, p38 MAP kinase or phosphodiesteras 5 inhibitors, antagonists of sphingosine-1-phosphate receptor 2, enhancing meningeal lymphatic drainage or with extracellular vesicles from mesenchymal stem cells; reducing GABAergic neurotransmission with indomethacin or golexanolone.<br><br>EXPERT OPINION: A factor limiting the progress of HE treatment is the lack of translation of research advances into clinical trials. Only drugs acting on microbiota or ammonia reduction have been tested in patients. It is urgent to change the mentality on how to approach HE treatment to develop clinical trials to assess drugs acting on the immune system/peripheral inflammation, neuroinflammation or neurotransmission to improve HE.}, }
@article {pmid37896894, year = {2023}, author = {Louge Uriarte, EL and Badaracco, A and Spetter, MJ and Miño, S and Armendano, JI and Zeller, M and Heylen, E and Späth, E and Leunda, MR and Moreira, AR and Matthijnssens, J and Parreño, V and Odeón, AC}, title = {Molecular Epidemiology of Rotavirus A in Calves: Evolutionary Analysis of a Bovine G8P[11] Strain and Spatio-Temporal Dynamics of G6 Lineages in the Americas.}, journal = {Viruses}, volume = {15}, number = {10}, pages = {}, pmid = {37896894}, issn = {1999-4915}, mesh = {Animals ; Cattle ; *Rotavirus/genetics ; Molecular Epidemiology ; Phylogeny ; *Rotavirus Infections/epidemiology/veterinary ; Diarrhea/epidemiology/veterinary ; Genotype ; Feces ; *Cattle Diseases/epidemiology ; }, abstract = {Rotavirus A (RVA) causes diarrhea in calves and frequently possesses the G6 and P[5]/P[11] genotypes, whereas G8 is less common. We aimed to compare RVA infections and G/P genotypes in beef and dairy calves from major livestock regions of Argentina, elucidate the evolutionary origin of a G8 strain and analyze the G8 lineages, infer the phylogenetic relationship of RVA field strains, and investigate the evolution and spatio-temporal dynamics of the main G6 lineages in American countries. Fecal samples (n = 422) from diarrheic (beef, 104; dairy, 137) and non-diarrheic (beef, 78; dairy, 103) calves were analyzed by ELISA and semi-nested multiplex RT-PCR. Sequencing, phylogenetic, phylodynamic, and phylogeographic analyses were performed. RVA infections were more frequent in beef (22.0%) than in dairy (14.2%) calves. Prevalent genotypes and G6 lineages were G6(IV)P[5] in beef (90.9%) and G6(III)P[11] (41.2%) or mixed genotypes (23.5%) in dairy calves. The only G8 strain was phylogenetically related to bovine and artiodactyl bovine-like strains. Re-analyses inside the G8 genotype identified G8(I) to G8(VIII) lineages. Of all G6 strains characterized, the G6(IV)P[5](I) strains from "Cuenca del Salado" (Argentina) and Uruguay clustered together. According to farm location, a clustering pattern for G6(IV)P[5] strains of beef farms was observed. Both G6 lineage strains together revealed an evolutionary rate of 1.24 × 10[-3] substitutions/site/year, and the time to the most recent common ancestor was dated in 1853. The most probable ancestral locations were Argentina in 1981 for G6(III) strains and the USA in 1940 for G6(IV) strains. The highest migration rates for both G6 lineages together were from Argentina to Brazil and Uruguay. Altogether, the epidemiology, genetic diversity, and phylogeny of RVA in calves can differ according to the production system and farm location. We provide novel knowledge about the evolutionary origin of a bovine G8P[11] strain. Finally, bovine G6 strains from American countries would have originated in the USA nearly a century before its first description.}, }
@article {pmid37895006, year = {2023}, author = {Kim, S and Noh, JH and Lee, MJ and Park, YJ and Kim, BM and Kim, YS and Hwang, S and Park, C and Kim, K}, title = {Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37895006}, issn = {1422-0067}, support = {NRF- 2020R1A2C3004508//National Research Foundation of Korea/ ; }, mesh = {Rats ; Animals ; *Transcriptome ; Mitochondria/genetics/metabolism ; Gene Expression Profiling ; *Sepsis/genetics/metabolism ; }, abstract = {Previously, we demonstrated that mitochondrial transplantation has beneficial effects in a polymicrobial sepsis model. However, the mechanism has not been fully investigated. Mitochondria have their own genes, and genomic changes in sepsis are an important issue in terms of pathophysiology, biomarkers, and therapeutic targets. To investigate the changes in transcriptomic features after mitochondrial transplantation in a polymicrobial sepsis model, we used a rat model of fecal slurry polymicrobial sepsis. Total RNA from splenocytes of sham-operated (SHAM, n = 10), sepsis-induced (SEPSIS, n = 7), and sepsis receiving mitochondrial transplantation (SEPSIS + MT, n = 8) samples was extracted and we conducted a comparative transcriptome-wide analysis between three groups. We also confirmed these results with qPCR. In terms of percentage of mitochondrial mapped reads, the SEPSIS + MT group had a significantly higher mapping ratio than the others. RT1-M2 and Cbln2 were identified as highly expressed in SEPSIS + MT compared with SEPSIS. Using SHAM expression levels as another control variable, we further identified six genes (Fxyd4, Apex2l1, Kctd4, 7SK, SNORD94, and SNORA53) that were highly expressed after sepsis induction and observed that their expression levels were attenuated by mitochondrial transplantation. Changes in transcriptomic features were identified after mitochondrial transplantation in sepsis. This might provide a hint for exploring the mechanism of mitochondrial transplantation in sepsis.}, }
@article {pmid37894615, year = {2023}, author = {Ni, Z and Li, J and Qian, X and Yong, Y and Wu, M and Wang, Y and Lv, W and Zhang, S and Zhang, Y and Shao, Y and Chen, A}, title = {Phellinus igniarius Polysaccharides Ameliorate Hyperglycemia by Modulating the Composition of the Gut Microbiota and Their Metabolites in Diabetic Mice.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {20}, pages = {}, pmid = {37894615}, issn = {1420-3049}, support = {BY2022773//Jiangsu Province's industry university research cooperation project/ ; BY2022777//Jiangsu Province's industry university research cooperation project/ ; KC22477//Xuzhou Science and Technology Program/ ; }, mesh = {Phellinus ; *Gastrointestinal Microbiome ; Polysaccharides/pharmacology/therapeutic use ; *Diabetes Mellitus, Type 2/drug therapy ; *Hyperglycemia/drug therapy ; Mice ; Animals ; *Diabetes Mellitus, Experimental ; Dysbiosis/drug therapy/microbiology ; }, abstract = {Gut microbiota dysbiosis has been reported as a risk factor in the development of type 2 diabetes mellitus (T2DM). Polysaccharides from Phellinus igniarius (P. igniarius) possess various properties that help manage metabolic diseases; however, their underlying mechanism of action remains unclear. Therefore, in this study, we aimed to evaluate the effect of P. igniarius polysaccharides (SH-P) on improving hyperglycemia in mice with T2DM and clarified its association with the modulation of gut microbiota and their metabolites using 16S rDNA sequencing and liquid chromatography-mass spectrometry. Fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. SH-P supplementation alleviated hyperglycemia symptoms in T2DM mice, ameliorated gut dysbiosis, and significantly increased the abundance of Lactobacillus in the gut. Pathway enrichment analysis indicated that SH-P treatment altered metabolic pathways associated with the occurrence and development of diabetes. Spearman's correlation analysis revealed that changes in the dominant bacterial genera were significantly correlated with metabolite levels closely associated with hyperglycemia. Additionally, FMT significantly improved insulin sensitivity and antioxidative capacity and reduced inflammation and tissue injuries, indicating improved glucose homeostasis. These results indicate that the ameliorative effects of SH-P on hyperglycemia are associated with the modulation of gut microbiota composition and its metabolites.}, }
@article {pmid37894194, year = {2023}, author = {Lopetuso, LR and Laterza, L and Petito, V and Pecere, S and Quaranta, G and Del Chierico, F and Puca, P and Schiavoni, E and Napolitano, D and Poscia, A and Ianiro, G and Pugliese, D and Putignani, L and Sanguinetti, M and Armuzzi, A and Masucci, L and Gasbarrini, A and Cammarota, G and Scaldaferri, F}, title = {Serial Fecal Microbiota Infusions via Colonoscopy for Active Ulcerative Colitis: A Feasibility, Safety, and Translational Monocentric Italian Study.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894194}, issn = {2076-2607}, abstract = {The effectiveness of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study aimed to investigate the feasibility and effectiveness of serial fecal infusions via colonoscopy in patients with active UC. Subjects with mild-to-moderate UC received three consecutive fecal infusions via colonoscopy. A control population with the same baseline features receiving Infliximab treatment was enrolled. Adverse events and clinical, endoscopic, and microbial outcomes were investigated. Nineteen patients with mildly-to-moderately active UC were enrolled. Clinical response was obtained in six patients at week 2, in eight at week 6, and in nine at week 12. Clinical response was maintained in eight patients at week 24. Endoscopic remission at week 12 was reached in six patients. In the control population, 13/19 patients achieved clinical response at week 6, and 10/19 patients maintained clinical response after 6 months. Microbiota richness was higher in responders compared with the non-responders. Peptostreptococcus, Lactobacillus, and Veillonella were higher in non-responders, while Parabacteroides, Bacteroides, Faecalibacterium, and Akkermansia were higher in responders at all timepoints. Serial FMT infusions appear to be feasible, safe, and effective in UC patients, with a potential role in inducing and maintaining clinical response. Specific bacteria predict the response to FMT.}, }
@article {pmid37894186, year = {2023}, author = {Beharry, KD and Latkowska, M and Valencia, AM and Allana, A and Soto, J and Cai, CL and Golombek, S and Hand, I and Aranda, JV}, title = {Factors Influencing Neonatal Gut Microbiome and Health with a Focus on Necrotizing Enterocolitis.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894186}, issn = {2076-2607}, abstract = {Maturational changes in the gut start in utero and rapidly progress after birth, with some functions becoming fully developed several months or years post birth including the acquisition of a full gut microbiome, which is made up of trillions of bacteria of thousands of species. Many factors influence the normal development of the neonatal and infantile microbiome, resulting in dysbiosis, which is associated with various interventions used for neonatal morbidities and survival. Extremely low gestational age neonates (<28 weeks' gestation) frequently experience recurring arterial oxygen desaturations, or apneas, during the first few weeks of life. Apnea, or the cessation of breathing lasting 15-20 s or more, occurs due to immature respiratory control and is commonly associated with intermittent hypoxia (IH). Chronic IH induces oxygen radical diseases of the neonate, including necrotizing enterocolitis (NEC), the most common and devastating gastrointestinal disease in preterm infants. NEC is associated with an immature intestinal structure and function and involves dysbiosis of the gut microbiome, inflammation, and necrosis of the intestinal mucosal layer. This review describes the factors that influence the neonatal gut microbiome and dysbiosis, which predispose preterm infants to NEC. Current and future management and therapies, including the avoidance of dysbiosis, the use of a human milk diet, probiotics, prebiotics, synbiotics, restricted antibiotics, and fecal transplantation, for the prevention of NEC and the promotion of a healthy gut microbiome are also reviewed. Interventions directed at boosting endogenous and/or exogenous antioxidant supplementation may not only help with prevention, but may also lessen the severity or shorten the course of the disease.}, }
@article {pmid37894065, year = {2023}, author = {Martinelli, S and Nannini, G and Cianchi, F and Staderini, F and Coratti, F and Amedei, A}, title = {Microbiota Transplant and Gynecological Disorders: The Bridge between Present and Future Treatments.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894065}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients' intestines to restore gut-immunity homeostasis. While FMT was primarily supposed to treat gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome-and especially Clostridium difficile infection (currently the only used as clinical treatment)-recent research has suggested that it may also become a potential treatment for gynecological disorders, including endometriosis and polycystic ovary syndrome (PCOS). On the contrary, vaginal microbiota transplantation (VMT) is a newer and less commonly used procedure than the FMT approach, and its potential applications are still being explored. It involves direct grafting of the entire vaginal microbiota of healthy women into the vaginal tract of patients to easily rebuild the local microbiota environment, restoring vaginal eubiosis and relieving symptoms. Like FMT, VMT is thought to have potential in treating different microbiota-related conditions. In fact, many gynecological disorders, such as bacterial vaginosis and vulvovaginal candidiasis, are thought to be caused by an imbalance in the vaginal microbiota. In this review, we will summarize the development, current challenges, and future perspectives of microbiota transplant, with the aim of exploring new strategies for its employment as a promising avenue for treating a broad range of gynecological diseases.}, }
@article {pmid37894027, year = {2023}, author = {Napolitano, M and Fasulo, E and Ungaro, F and Massimino, L and Sinagra, E and Danese, S and Mandarino, FV}, title = {Gut Dysbiosis in Irritable Bowel Syndrome: A Narrative Review on Correlation with Disease Subtypes and Novel Therapeutic Implications.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894027}, issn = {2076-2607}, abstract = {Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, and unclassified. Over the past decade, the role of gut microbiota in IBS has garnered significant attention in the scientific community. Emerging research spotlights the intricate involvement of microbiota dysbiosis in IBS pathogenesis. Studies have demonstrated reduced microbial diversity and stability and specific microbial alterations for each disease subgroup. Microbiota-targeted treatments, such as antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and even diet, offer exciting prospects for managing IBS. However, definitive conclusions are hindered by the heterogeneity of these studies. Further research should focus on elucidating the mechanisms, developing microbiome-based diagnostics, and enabling personalized therapies tailored to an individual's microbiome profile. This review takes a deep dive into the microscopic world inhabiting our guts, and its implications for IBS. Our aim is to elucidate the complex interplay between gut microbiota and each IBS subtype, exploring novel microbiota-targeted treatments and providing a comprehensive overview of the current state of knowledge.}, }
@article {pmid37892453, year = {2023}, author = {Wu, S and Wu, Z and Chen, Y}, title = {Effect of Cordyceps militaris Powder Prophylactic Supplementation on Intestinal Mucosal Barrier Impairment and Microbiota-Metabolites Axis in DSS-Injured Mice.}, journal = {Nutrients}, volume = {15}, number = {20}, pages = {}, pmid = {37892453}, issn = {2072-6643}, support = {82070543//National Natural Science Foundation of China/ ; 82270581//National Natural Science Foundation of China/ ; 2021YFA0717001//National Key R&amp;D Program of China/ ; KCXFZ20211020163558024//Shenzhen Science and Technology Planning Project/ ; ZDSYS20220606100800002//Shenzhen Science and Technology Program/ ; }, mesh = {Humans ; Animals ; Mice ; *Cordyceps ; Powders ; *Microbiota ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/chemically induced/prevention &amp; control ; *Food Ingredients ; Dietary Supplements ; Dextran Sulfate ; Disease Models, Animal ; Mice, Inbred C57BL ; *Colitis ; Colon ; }, abstract = {Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease with an unknown pathogenesis and increasing incidence. The objective of this study is to investigate the impact of prophylactic treatment with Cordyceps militaris on UC. The findings demonstrate that prophylactic supplementation of C. militaris powder effectively mitigates disease symptoms in DSS-injured mice, while also reducing the secretion of pro-inflammatory cytokines. Furthermore, C. militaris powder enhances the integrity of the intestinal mucosal barrier by up-regulating MUC2 protein expression and improving tight junction proteins (ZO-1, occludin, and claudin 1) in DSS-injured mice. Multiomics integration analyses revealed that C. militaris powder not only reshaped gut microbiota composition, with an increase in Lactobacillus, Odoribacter, and Mucispirillum, but also exerted regulatory effects on various metabolic pathways including amino acid, glyoxylates, dicarboxylates, glycerophospholipids, and arachidonic acid. Subsequent analysis further elucidated the intricate interplay of gut microbiota, the intestinal mucosal barrier, and metabolites, suggesting that the microbiota-metabolite axis may involve the effect of C. militaris on intestinal mucosal barrier repair in UC. Moreover, in vitro experiments demonstrated that peptides and polysaccharides, derived from C. militaris, exerted an ability to change the gut microbiota structure of UC patients' feces, particularly by promoting the growth of Lactobacillus. These findings suggest that regulatory properties of C. militaris on gut microbiota may underlie the potential mechanism responsible for the protective effect of C. militaris in UC. Consequently, our study will provide support for the utilization of C. militaris as a whole food-based ingredient against the occurrence and development of UC.}, }
@article {pmid37891616, year = {2023}, author = {Moreno, AF and Lavín-Alconero, L and de Ugarriza, PL and Blanco, LS and Hernández, SC and Burgués, JMB and de Miguel, MI and Huerta, AJG and Zarzuela, MP and Boluda, B and Humala, K and Calabuig, ML and Amigo, ML and Casas, MC and Del Mar García-Saiz, M and Verdugo, AF and Domínguez, JF and Bernal, T}, title = {FOVOCIP study: a multicenter randomized trial of fosfomycin versus ciprofloxacin for febrile neutropenia in hematologic patients-efficacy and microbiologic safety.}, journal = {Trials}, volume = {24}, number = {1}, pages = {694}, pmid = {37891616}, issn = {1745-6215}, support = {FIS PI21/01590//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; Ciprofloxacin/adverse effects ; *Fosfomycin/therapeutic use ; *Hematopoietic Stem Cell Transplantation ; *Leukemia, Myeloid, Acute ; *Febrile Neutropenia/diagnosis/drug therapy ; Anti-Bacterial Agents/adverse effects ; }, abstract = {BACKGROUND: Multidrug-resistant Gram-negative bacterial (MRGNB) infections represent a major public health threat. Cancer patients and, among them, hematological patients are most vulnerable to these infections. Gut colonization by MRGNB is a common phenomenon occurring during hospitalization and chemotherapy exposure. In the neutropenic phase that occurs after chemotherapy, MRGNB translocation occurs increasing patient's mortality. Fluoroquinolone prophylaxis with ciprofloxacin or levofloxacin efficacy is now being questioned due to the increase of incidence in MRGNB.<br><br>METHODS: A phase III randomized, controlled, clinical trial, open-label parallel-group with a 1:1 ratio, aimed to demonstrate the non-inferiority of oral fosfomycin versus oral ciprofloxacin for febrile neutropenia prevention in patients with acute leukemia (AL) or hematopoietic cell transplant (HSC) receptors. Weekly surveillance cultures are planned to detect gut colonization. Changes in fecal microbiome at the beginning and end of prophylaxis will also be analyzed.<br><br>DISCUSSION: This trial will provide evidence of the efficacy of an alternative drug to ciprofloxacin for febrile neutropenia prevention in high-risk hematological patients. The battery of planned microbiological studies will allow us to evaluate prospectively the microbiological safety of both pharmacological strategies in terms of the selection of MRGNB occurring in each arm. In addition, valuable information on the way in which each drug changes the fecal microbiome of the patients throughout the treatment will be generated.<br><br>TRIAL REGISTRATION: Clinical trials NCT05311254, Registered on 5 April 2022, https://clinicaltrials.gov/ct2/show/NCT05311254?term=FOVOCIP&amp;cntry=ES&amp;draw=2&amp;rank=1 .<br><br>PROTOCOL VERSION: 3.0, dated 20 May 2022.}, }
@article {pmid37888102, year = {2023}, author = {Kaltsas, A and Zachariou, A and Markou, E and Dimitriadis, F and Sofikitis, N and Pournaras, S}, title = {Microbial Dysbiosis and Male Infertility: Understanding the Impact and Exploring Therapeutic Interventions.}, journal = {Journal of personalized medicine}, volume = {13}, number = {10}, pages = {}, pmid = {37888102}, issn = {2075-4426}, abstract = {The human microbiota in the genital tract is pivotal for maintaining fertility, but its disruption can lead to male infertility. This study examines the relationship between microbial dysbiosis and male infertility, underscoring the promise of precision medicine in this field. Through a comprehensive review, this research indicates microbial signatures associated with male infertility, such as altered bacterial diversity, the dominance of pathogenic species, and imbalances in the genital microbiome. Key mechanisms linking microbial dysbiosis to infertility include inflammation, oxidative stress, and sperm structural deterioration. Emerging strategies like targeted antimicrobial therapies, probiotics, prebiotics, and fecal microbiota transplantation have shown potential in adjusting the genital microbiota to enhance male fertility. Notably, the application of precision medicine, which customizes treatments based on individual microbial profiles and specific causes of infertility, emerges as a promising approach to enhance treatment outcomes. Ultimately, microbial dysbiosis is intricately linked to male infertility, and embracing personalized treatment strategies rooted in precision medicine principles could be the way forward in addressing infertility associated with microbial factors.}, }
@article {pmid37887364, year = {2023}, author = {Jess, AT and Eskander, GH and Vu, MH and Michail, S}, title = {Short-Chain Fatty Acid Levels after Fecal Microbiota Transplantation in a Pediatric Cohort with Recurrent Clostridioides difficile Infection.}, journal = {Metabolites}, volume = {13}, number = {10}, pages = {}, pmid = {37887364}, issn = {2218-1989}, support = {UL1 TR000130/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; }, abstract = {Though antibiotics are the mainstay treatment for Clostridioides difficile, a large population of individuals infected will experience recurrence. In turn, fecal microbiota transplantation (FMT) has emerged as a promising treatment for recurrent C. difficile infection (rCDI). Mechanistically, by providing a healthy, diverse flora to the infected individual, FMT "resets" the underlying gut microbiome dysbiosis associated with rCDI. A proposed mechanism through which this occurs is via microbiome metabolites such as short-chain fatty acids (SCFAs); however, this has not been previously studied in pediatric patients. Using mass spectroscopy, we quantified pre- and post-transplant levels of acetate, isovalerate, butyrate, formate, and propionate in pediatric patients diagnosed with rCDI (n = 9). We compared pre- and post-transplant levels within the rCDI cohort at 1, 3, 6, and 12 months post-transplant and correlated these levels with healthy controls (n = 19). We witnessed a significant difference in the combined SCFA levels and the individual levels of acetate, butyrate, isovalerate, and propionate in the pre-treatment rCDI cohort compared to the healthy controls. In addition, there was a significant increase in combined SCFA levels at 12 months post-transplant within the rCDI group compared to that of their pre-transplant levels, and, more specifically, acetate, propionate, and isovalerate increased from pre-transplant to 12 months post-transplant. The longitudinal aspect of this study allowed us to identify mechanisms that contribute to the durability of responses to FMT, as well as characterize the unique patterns of short-chain fatty acid level recovery in rCDI pediatric patients.}, }
@article {pmid37887204, year = {2023}, author = {Pang, J and Beyi, AF and Looft, T and Zhang, Q and Sahin, O}, title = {Fecal Microbiota Transplantation Reduces Campylobacter jejuni Colonization in Young Broiler Chickens Challenged by Oral Gavage but Not by Seeder Birds.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {37887204}, issn = {2079-6382}, support = {2018-67017-28117//United States Department of Agriculture/ ; }, abstract = {Campylobacter spp., particularly C. jejuni and C. coli, are major food safety concerns, transmitted to humans mainly via contaminated poultry meat. In a previous study, we found that some commercial broiler farms consistently produced Campylobacter-free flocks while others consistently reared Campylobacter-colonized flocks, and significant differences in the gut microbiota compositions between the two types of farm categories were revealed. Therefore, we hypothesized that gut microbiota influences Campylobacter colonization in poultry and that the microbiota from Campylobacter-free flocks may confer colonization resistance to Campylobacter in the chicken intestine. In this study, two fecal microbiota transplantation (FMT) trials were performed to test the hypothesis. Newly hatched chicks were given FMT via oral gavage of the cecal content of Campylobacter-free adult chickens (treatment groups) or PBS (control groups) before the feed consumption. Approximately two weeks after the FMT, the birds were challenged with C. jejuni either by oral gavage (trial 1) or by co-mingling with Campylobacter-colonized seeder birds (trial 2) to evaluate the potential protective effect of the FMT. Cecal contents were collected (3 times, 5 days apart) to determine the Campylobacter colonization levels via culture and microbiota compositions via 16S rRNA gene sequencing. FMT reduced cecal Campylobacter colonization significantly (log10 1.2-2.54 CFU/g) in trial 1 but not in trial 2, although FMT significantly impacted the diversity and compositions of the gut microbiota in both trials. Several genera, such as Butyricimonas, Parabacteroides, Parasutterella, Bilophila, Fournierella, Phascolarctobacterium, and Helicobacter, had increased abundance in the FMT-treated groups in both trials. Furthermore, Campylobacter abundance was found to be negatively correlated with the Escherichia and Ruminococcus_torques_group genera. These findings indicate that even though FMT with adult cecal microbiota can positively affect the subsequent development of the gut microbiota in young broilers, its inhibitory effect on Campylobacter colonization varies and appears to be influenced by the challenge models.}, }
@article {pmid37885166, year = {2023}, author = {El-Salhy, M and Gilja, OH and Hatlebakk, JG}, title = {Letter: A step forward towards a standard FMT protocol for IBS.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {58}, number = {10}, pages = {1115-1116}, doi = {10.1111/apt.17749}, pmid = {37885166}, issn = {1365-2036}, mesh = {Feces ; *Irritable Bowel Syndrome/diagnosis/therapy ; Semustine ; Fluorouracil ; Triazines ; Antineoplastic Combined Chemotherapy Protocols ; Treatment Outcome ; Humans ; Fecal Microbiota Transplantation/methods ; }, }
@article {pmid37879794, year = {2023}, author = {Liu, Y and Wu, H and Wang, T and Shi, X and He, H and Huang, H and Yang, Y and Dai, M}, title = {Paeonol reduces microbial metabolite α-hydroxyisobutyric acid to alleviate the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in atherosclerosis mice.}, journal = {Chinese journal of natural medicines}, volume = {21}, number = {10}, pages = {759-774}, doi = {10.1016/S1875-5364(23)60506-0}, pmid = {37879794}, issn = {1875-5364}, mesh = {Animals ; Mice ; *Atherosclerosis/drug therapy ; Diet, High-Fat ; Endothelial Cells ; Inflammation/drug therapy ; Mice, Inbred C57BL ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; Reactive Oxygen Species ; }, abstract = {Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE[-/-] mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg[-1]) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.}, }
@article {pmid37879793, year = {2023}, author = {Zhou, J and Fan, Q and Cai, X and Zhang, Y and Hou, Y and Cao, S and Li, Z and Feng, M and Wang, Q and Zhang, J and Wang, G and Zheng, X and Hao, H}, title = {Ginkgo biloba extract protects against depression-like behavior in mice through regulating gut microbial bile acid metabolism.}, journal = {Chinese journal of natural medicines}, volume = {21}, number = {10}, pages = {745-758}, doi = {10.1016/S1875-5364(23)60496-0}, pmid = {37879793}, issn = {1875-5364}, mesh = {Humans ; Mice ; Animals ; *Depression/drug therapy ; *Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba ; }, abstract = {Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.}, }
@article {pmid37873265, year = {2023}, author = {Chang, D and Gupta, VK and Hur, B and Cobo-López, S and Cunningham, KY and Han, NS and Lee, I and Kronzer, VL and Teigen, LM and Karnatovskaia, LV and Longbrake, EE and Davis, JM and Nelson, H and Sung, J}, title = {Gut Microbiome Wellness Index 2 for Enhanced Health Status Prediction from Gut Microbiome Taxonomic Profiles.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37873265}, issn = {2692-8205}, support = {UL1 TR002377/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; }, abstract = {Recent advancements in human gut microbiome research have revealed its crucial role in shaping innovative predictive healthcare applications. We introduce Gut Microbiome Wellness Index 2 (GMWI2), an advanced iteration of our original GMWI prototype, designed as a robust, disease-agnostic health status indicator based on gut microbiome taxonomic profiles. Our analysis involved pooling existing 8069 stool shotgun metagenome data across a global demographic landscape to effectively capture biological signals linking gut taxonomies to health. GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence (i.e., outside the "reject option"). The enhanced classification accuracy of GMWI2 outperforms both the original GMWI model and traditional species-level α-diversity indices, suggesting a more reliable tool for differentiating between healthy and non-healthy phenotypes using gut microbiome data. Furthermore, by reevaluating and reinterpreting previously published data, GMWI2 provides fresh insights into the established understanding of how diet, antibiotic exposure, and fecal microbiota transplantation influence gut health. Looking ahead, GMWI2 represents a timely pivotal tool for evaluating health based on an individual's unique gut microbial composition, paving the way for the early screening of adverse gut health shifts. GMWI2 is offered as an open-source command-line tool, ensuring it is both accessible to and adaptable for researchers interested in the translational applications of human gut microbiome science.}, }
@article {pmid37872499, year = {2023}, author = {Skjevling, LK and Hanssen, HM and Valle, PC and Goll, R and Juul, FE and Arlov, &#xd8; and Johnsen, PH}, title = {Colonic distribution of FMT by different enema procedures compared to colonoscopy - proof of concept study using contrast fluid.}, journal = {BMC gastroenterology}, volume = {23}, number = {1}, pages = {363}, pmid = {37872499}, issn = {1471-230X}, mesh = {Humans ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Colon/diagnostic imaging ; Colonoscopy ; Cross-Over Studies ; Enema ; Fecal Microbiota Transplantation/methods ; Feces ; Proof of Concept Study ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has become an important treatment method in recurrent Clostridioides difficile infections and is under investigation as a treatment for several other diseases. FMT's mechanism of action is assumed to be through alterations of the colon microbiota. FMT can be delivered by several methods, but few studies have directly compared how FMT is distributed in the colon by different methods. Specifically, the proximal distribution of FMT delivered by enema is unknown.<br><br>METHODS: In eight participants, we administered contrast fluid (CF) with viscosity similar to an FMT in a crossover study design. First, CF was administered by colonoscopy, followed by an abdominal X-ray to visualize the CF distribution. Next, after four to eight weeks, participants were given CF, but as an enema, followed by a positioning procedure. X-rays were obtained before (enema &#xf7;) and after (enema +) the positioning procedure.<br><br>CONCLUSION: Proportion of participants with CF in cecum were 100% after colonoscopy, 50% after enema&#x2009;+&#x2009;and 38% after enema &#xf7;. In the transverse colon, proportions were 100% (colonoscopy), 88% (enema +) and 63% (enema &#xf7;). There were no adverse events.<br><br>INTERPRETATION: This study shows proof of concept for the distribution of FMT to proximal colon when delivered by enema. A positioning procedure after the enema slightly improves the proximal distribution. However, colonoscopy is the only method that ensures delivery to the cecum. Studies are needed to see if FMT colon distribution correlates with treatment effectiveness.<br><br>TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov (NCT05121285) (16/11/2021).}, }
@article {pmid37872356, year = {2024}, author = {Jadhav, G and Dudhabhate, BB and Kokare, DM and Sakharkar, AJ}, title = {Gut Microbiota Regulates Epigenetic Remodelling in the Amygdala: A Role in Repeated Mild Traumatic Brain Injury (rMTBI)-Induced Anxiety.}, journal = {Molecular neurobiology}, volume = {61}, number = {12}, pages = {9892-9914}, pmid = {37872356}, issn = {1559-1182}, support = {RUSA-CBS-TH 4.5//Rashtriya Uchchatar Shiksha Abhiyan/ ; CRG/2020/004971//Science and Engineering Research Board (IN), SERB/ ; }, mesh = {Animals ; Male ; *Gastrointestinal Microbiome/physiology ; *Anxiety/microbiology ; *Epigenesis, Genetic ; *Amygdala/metabolism ; *Rats, Wistar ; *Brain-Derived Neurotrophic Factor/metabolism ; DNA Methylation/genetics ; Fecal Microbiota Transplantation ; Rats ; Dysbiosis ; Neuronal Plasticity/physiology ; }, abstract = {Gut microbiota serves in the development and maintenance of phenotype. However, the underlying mechanisms are still in its infancy. The current study shows epigenetic remodelling in the brain as a causal mechanism in the gut microbiota-brain axis. Like in trauma patients, gut dysbiosis and anxiety were comorbid in adult male Wistar rats subjected to repeated mild traumatic brain injuries (rMTBI). rMTBI caused epigenetic dysregulation of brain-derived neurotrophic factor (Bdnf) expression in the amygdala, owing to the formation of transcriptional co-repressor complex due to dynamic interaction between histone deacetylase and DNA methylation modification at the Bdnf gene promoter. The probiosis after faecal microbiota transplantation (FMT) from healthy naïve rats or by administration of single strain probiotic (SSP), Lactobacillus rhamnosus GG (LGG), recuperated rMTBI-induced anxiety. Concurrently, LGG infusion or naïve FMT also dislodged rMTBI-induced co-repressor complex resulting in the normalization of Bdnf expression and neuronal plasticity as measured by Golgi-Cox staining. Furthermore, sodium butyrate, a short-chain fatty acid, produced neurobehavioural effects similar to naïve FMT or LGG administration. Interestingly, the gut microbiota from rMTBI-exposed rats per se was able to provoke anxiety in naïve rats in parallel with BDNF deficits. Therefore, gut microbiota seems to be causally linked with the chromatin remodelling necessary for neuroadaptations via neuronal plasticity which drives experience-dependent behavioural manifestations.}, }
@article {pmid37871256, year = {2023}, author = {Peled, JU and van den Brink, MRM}, title = {Fecal Transplantation in Hematopoietic Transplantation.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {41}, number = {34}, pages = {5320-5323}, pmid = {37871256}, issn = {1527-7755}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Fecal Microbiota Transplantation ; *Hematopoietic Stem Cell Transplantation ; *Graft vs Host Disease/etiology/prevention &amp; control ; }, }
@article {pmid37870235, year = {2024}, author = {Duan, R and von Ehrlich-Treuenstätt, VH and Kakoschke, SC and Schardey, J and Wirth, U and Albertsmeier, M and Renz, BW and Andrassy, J and Bazhin, AV and Hodin, RA and Werner, J and Ilmer, M and Kühn, F}, title = {Effect of Surgery on Postoperative Levels of the Gut Homeostasis-Regulating Enzyme Intestinal Alkaline Phosphatase.}, journal = {Journal of the American College of Surgeons}, volume = {238}, number = {1}, pages = {70-80}, doi = {10.1097/XCS.0000000000000879}, pmid = {37870235}, issn = {1879-1190}, mesh = {Humans ; *Alkaline Phosphatase/metabolism/physiology ; Homeostasis ; Intestinal Mucosa ; *Lipopolysaccharides ; Postoperative Period ; *Pancreaticoduodenectomy/adverse effects/rehabilitation ; }, abstract = {BACKGROUND: Intestinal homeostasis is a crucial factor for complication-free short- and long-term postoperative recovery. The brush border enzyme intestinal alkaline phosphatase (IAP) is an important regulator of gut barrier function and intestinal homeostasis and prevents endotoxemia by detoxifying lipopolysaccharides (LPSs). As IAP is predominantly secreted by enterocytes in the duodenum, we hypothesized that pancreaticoduodenectomy (PD) leads to a significantly stronger decrease in IAP than other major abdominal surgery.<br><br>STUDY DESIGN: Pre- and postoperative blood, stool, and intestinal samples were collected from patients undergoing PD, as well as other major surgical procedures without duodenectomy. The samples were analyzed using enzyme histochemistry, the para -nitrophenyl phosphate method for IAP, and the limulus amebocyte lysate assay for LPS.<br><br>RESULTS: Overall, 88 patients were prospectively enrolled in the study. Fecal IAP activity negatively correlated with serum LPS (r = -0.3603, p = 0.0006). PD led to a significant decline in IAP compared to preoperative baseline levels (p < 0.0001). The decline in IAP correlated with the length of proximal small intestinal resection (r = 0.4271, p = 0.0034). Compared to controls, PD was associated with a much more pronounced reduction in IAP-also after adjusting for surgical trauma (operative time, blood loss; r = 0.4598, p = 0.0086). Simultaneously, PD triggered a clearly more prominent increase in serum LPS compared to controls (p = 0.0001). Increased postoperative LPS was associated with an elongated hospitalization (r = 0.7534, p = 0.0062) and more prominent in pancreatic cancer (p = 0.0009).<br><br>CONCLUSIONS: Based upon the functional roles for IAP, supplementation with exogenous IAP might be a new treatment option to improve short- and long-term outcome after PD.}, }
@article {pmid37868345, year = {2023}, author = {Yuan, C and He, Y and Xie, K and Feng, L and Gao, S and Cai, L}, title = {Review of microbiota gut brain axis and innate immunity in inflammatory and infective diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1282431}, pmid = {37868345}, issn = {2235-2988}, mesh = {Humans ; Brain-Gut Axis ; *Autism Spectrum Disorder ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; Immunity, Innate ; *Communicable Diseases ; Brain ; }, abstract = {The microbiota gut brain (MGB) axis has been shown to play a significant role in the regulation of inflammatory and infective diseases. Exploring the structure and communication mode of MGB axis is crucial for understanding its role in diseases, and studying the signaling pathways and regulatory methods of MGB axis regulation in diseases is also of profound significance for future clinical research. This article reviews the composition, communication mechanism of MGB axis and its role in inflammatory and infective diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD), depression, psoriasis, irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBD). In addition, our investigation delved into the regulatory functions of the inflammasome, IFN-I, NF-κB, and PARK7/DJ-1 innate immune signaling pathway in the context of inflammatory and infective diseases. Ultimately, we discussed the efficacy of various interventions, including fecal microbiota transplantation (FMT), antibiotics, probiotics, prebiotics, synbiotics, and postbiotics, in the management of inflammatory and infective diseases. Understanding the role and mechanism of the MGB axis might make positive effects in the treatment of inflammatory and infective diseases.}, }
@article {pmid37867202, year = {2023}, author = {Ma, J and Wen, S and Dong, A and Fan, W and Kang, Y}, title = {Gut Microbiome (Bacteria, Fungi, and Viruses) and HIV Infection: Revealing Novel Treatment Strategies.}, journal = {Molecular nutrition &amp; food research}, volume = {67}, number = {23}, pages = {e2300566}, doi = {10.1002/mnfr.202300566}, pmid = {37867202}, issn = {1613-4133}, support = {202103021223240//Natural Science Foundation of Shanxi Province for Youths/ ; SD2009//Science Research Start-up Fund of Shanxi Province for Doctors/ ; XD2014//Science Research Start-up Fund of Shanxi Medical University for Doctor/ ; 2021L217//Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *HIV Infections/therapy ; *Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation/methods ; Bacteria ; Fungi ; *Viruses ; }, abstract = {Plenty of research on microbial-viral interactions has revealed that some commensal microorganisms in the gut, including bacteria, fungi, and viruses, can resist or promote viral infection, whereas other microorganisms are involved in pathogenicity. Therefore, the balance between commensal microorganisms and human organisms is a key factor for determining infection and disease progression, and commensal microorganisms have become a hot research area in the medical field. In this review, the compositional characteristics of gut microbiota (bacteria, fungi, and viruses) during HIV infection are reviewed and changes in gut microbiota among different HIV-infected populations are described. Furthermore, the latest progress of potential microbial therapeutic methods, including a) probiotics, prebiotics, and synbiotics, b) fecal microbiota transplantation (FMT), c) phage therapy, and d) antifungal strategy, microbial enzyme inhibition, and dietary therapeutics, is analyzed based on gut bacteria, fungi, and viruses in the field of HIV infection. This study aims to provide a useful reference for developing novel strategies for the prevention and treatment of HIV infection based on commensal microorganisms.}, }
@article {pmid37865904, year = {2023}, author = {Clifford, T}, title = {Practice Corner: Fecal Microbiota Transplant.}, journal = {Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses}, volume = {38}, number = {6}, pages = {950-951}, doi = {10.1016/j.jopan.2023.08.011}, pmid = {37865904}, issn = {1532-8473}, mesh = {*Fecal Microbiota Transplantation ; }, }
@article {pmid37865177, year = {2023}, author = {Guha, L and Agnihotri, TG and Jain, A and Kumar, H}, title = {Gut microbiota and traumatic central nervous system injuries: Insights into pathophysiology and therapeutic approaches.}, journal = {Life sciences}, volume = {334}, number = {}, pages = {122193}, doi = {10.1016/j.lfs.2023.122193}, pmid = {37865177}, issn = {1879-0631}, mesh = {Humans ; *Gastrointestinal Microbiome ; Central Nervous System ; *Brain Injuries, Traumatic/therapy/metabolism ; Prebiotics ; *Spinal Cord Injuries/metabolism ; Brain/metabolism ; }, abstract = {Traumatic brain injury and spinal cord injury are two distinct but fundamentally similar types of acute insults to the central nervous system (CNS) that often culminate in death or cognitive and motor impairment. Over the past decade, researchers have tapped into research to discover the potential role being played by gut bacteria in CNS. After an acute CNS injury, the altered composition of the gut microbiota disturbs the balance of the bidirectional gut-brain axis, aggravating secondary CNS injury, motor dysfunctions, and cognitive deficits, which worsens the patient's prognosis. Some of the well-known therapeutic interventions which can also be used as adjuvant therapy for alleviating CNS injuries include, the use of pro and prebiotics, fecal microbiota transplantation, and microbial engineering. In this review, we aim to discuss the importance of gut microbes in our nervous system, anatomy, and signaling pathways involved in regulating the gut-brain axis, the alteration of the gut microbiome in CNS injuries, and the therapeutic strategies to target gut microbiomes in traumatic CNS injuries.}, }
@article {pmid37863204, year = {2023}, author = {Guan, Y and Liu, T and Xu, F and Xie, S and Gu, W and Bie, Y}, title = {Integration of 16S rRNA gene sequencing and LC/MS-based metabolomic analysis of early biomarkers of acute ischaemic stroke in Tibetan miniature pigs.}, journal = {Journal of microbiological methods}, volume = {215}, number = {}, pages = {106846}, doi = {10.1016/j.mimet.2023.106846}, pmid = {37863204}, issn = {1872-8359}, mesh = {Animals ; Swine ; Swine, Miniature/genetics ; RNA, Ribosomal, 16S/genetics/analysis ; Tibet ; *Brain Ischemia/genetics ; Genes, rRNA ; Feces/microbiology ; *Stroke/genetics ; Metabolomics/methods ; Metabolome ; Biomarkers/analysis ; *Ischemic Stroke/genetics ; ATP-Binding Cassette Transporters/genetics ; }, abstract = {Acute ischaemic stroke (AIS) is a complex, systemic, pathological, and physiological process. Systemic inflammatory responses and disorders of the gut microbiome contribute to increased mortality and disability following AIS. We conducted 16S high-throughput sequencing and ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry-based non-targeted metabolomic analyses of the plasma from a Tibetan miniature pig middle cerebral artery occlusion (MCAO) model. A significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Actinobacteria were observed after the onset of AIS. Among the plasma metabolites, the levels of phospholipids and amino acids were considerably altered. Loading values and differential metabolite-bacterial group association analyses of the metabolome and microbiome indicated a correlation between the microbiome and metabolome of Tibetan miniature pigs after MCAO. Furthermore, significant changes were observed in the ABC transporter pathway and purine metabolism in the gut microbiome-plasma metabolome during the early stage of AIS. Kyoto Encyclopaedia of Genes and Genomes enrichment analysis showed that arginine, proline, and cyanoamino acid metabolism was upregulated while ABC transporter metabolism pathway and carbohydrate digestion and absorption were substantially downregulated. The results of this study suggest that AIS affects the gut microbiota and plasma metabolites in Tibetan miniature pigs and that faecal microbiota transplantation could be a potential therapeutic approach for AIS.}, }
@article {pmid37862466, year = {2023}, author = {Diaz, LA and Winder, GS and Leggio, L and Bajaj, JS and Bataller, R and Arab, JP}, title = {New insights into the molecular basis of alcohol abstinence and relapse in alcohol-associated liver disease.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, pmid = {37862466}, issn = {1527-3350}, abstract = {Alcohol use disorder remains a significant public health concern, affecting around 5% of adults worldwide. Novel pathways of damage have been described during the last years, providing insight into the mechanism of injury due to alcohol misuse beyond the direct effect of ethanol byproducts on the liver parenchyma and neurobehavioral mechanisms. Thus, the gut-liver-brain axis and immune system involvement could be therapeutic targets for alcohol use disorder. In particular, changes in gut microbiota composition and function, and bile acid homeostasis, have been shown with alcohol consumption and cessation. Alcohol can also directly disrupt intestinal and blood-brain barriers. Activation of the immune system can be triggered by intestinal barrier dysfunction and translocation of bacteria, pathogen-associated molecular patterns (such as lipopolysaccharide), cytokines, and damage-associated molecular patterns. These factors, in turn, promote liver and brain inflammation and the progression of liver fibrosis. Other involved mechanisms include oxidative stress, apoptosis, autophagy, and the release of extracellular vesicles and miRNA from hepatocytes. Potential therapeutic targets include gut microbiota (probiotics and fecal microbiota transplantation), neuroinflammatory pathways, as well as neuroendocrine pathways, for example, the ghrelin system (ghrelin receptor blockade), incretin mimetics (glucagon-like peptide-1 analogs), and the mineralocorticoid receptor system (spironolactone). In addition, support with psychological and behavioral treatments is essential to address the multiple dimensions of alcohol use disorder. In the future, a personalized approach considering these novel targets can contribute to significantly decreasing the alcohol-associated burden of disease.}, }
@article {pmid37860535, year = {2023}, author = {Ma, L and Song, J and Chen, X and Dai, D and Chen, J and Zhang, L}, title = {Fecal microbiota transplantation regulates TFH/TFR cell imbalance via TLR/MyD88 pathway in experimental autoimmune hepatitis.}, journal = {Heliyon}, volume = {9}, number = {10}, pages = {e20591}, pmid = {37860535}, issn = {2405-8440}, abstract = {OBJECTIVE: Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. Intestinal flora disturbance in AIH is closely related to TFH/TFR cell imbalances. As a new method of microbial therapy, the role of fecal microbiota transplantation (FMT) in AIH remains elusive. Here, we attempted to verify the functional role and molecular mechanism of FMT in AIH.<br><br>METHODS: An experimental autoimmune hepatitis (EAH) mouse model was established to mimic the characteristics of AIH. H&amp;E staining was used to detect histological features in mouse liver tissues. Serological tests were employed to identify several liver function biomarkers. Flow cytometry was utilized to examine the status of TFH/TFR cell subsets. Western blotting was used to evaluate TLR pathway-associated protein abundance. RT&#x2012;qPCR was applied to evaluate Treg cell markers and inflammation marker levels in mouse liver tissues.<br><br>RESULTS: There was significant liver inflammation and dysregulated TFR/TFH cells with elevated levels of liver inflammation-associated biomarkers in EAH mice. Interestingly, transferring therapeutic FMT into EAH mice dramatically reduced liver injury and improved the imbalance between splenic TFR and TFH cells. FMT treatment also reduced elevated contents of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in EAH mice. Furthermore, therapeutic FMT reversed the increased levels of IL-21 while promoting IL-10 and TGF-&#x3b2; cytokines. Mechanistically, FMT regulated TFH cell response in EAH mice in a TLR4/11/MyD88 pathway-dependent manner.<br><br>CONCLUSION: Our findings demonstrated that liver injury and dysregulation between TFR and TFH cells in EAH might be reversed by therapeutic FMT via the TLR4/11-MyD88 signaling pathway.}, }
@article {pmid37858797, year = {2024}, author = {Yang, J and Wei, H and Lin, Y and Chu, ESH and Zhou, Y and Gou, H and Guo, S and Lau, HCH and Cheung, AHK and Chen, H and To, KF and Sung, JJY and Wang, Y and Yu, J}, title = {High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice.}, journal = {Gastroenterology}, volume = {166}, number = {2}, pages = {323-337.e7}, doi = {10.1053/j.gastro.2023.10.012}, pmid = {37858797}, issn = {1528-0012}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Inulin/pharmacology ; Mice, Inbred C57BL ; Carcinogenesis ; Dietary Fiber/metabolism ; Cellulose/pharmacology ; Azoxymethane ; *Colorectal Neoplasms/pathology ; }, abstract = {BACKGROUND &amp; AIMS: Dietary fibers are mainly fermented by the gut microbiota, but their roles in colorectal cancer (CRC) are largely unclear. Here, we investigated the associations of different fibers with colorectal tumorigenesis in mice.<br><br>METHODS: Apc[min/+] mice and C57BL/6 mice with azoxymethane (AOM) injection were used as CRC mouse models. Mice were fed with mixed high-fiber diet (20% soluble fiber and 20% insoluble fiber), high-inulin diet, high-guar gum diet, high-cellulose diet, or diets with different inulin dose. Germ-free mice were used for validation. Fecal microbiota and metabolites were profiled by shotgun metagenomic sequencing and liquid chromatography-mass spectrometry, respectively.<br><br>RESULTS: Mixed high-fiber diet promoted colorectal tumorigenesis with increased tumor number and tumor load in AOM-treated and Apc[min/+] mice. Antibiotics use abolished the pro-tumorigenic effect of mixed high-fiber diet, while transplanting stools from mice fed with mixed high-fiber diet accelerated tumor growth in AOM-treated germ-free mice. We therefore characterized the contribution of soluble and insoluble fiber in CRC separately. Our results revealed that soluble fiber inulin or guar gum, but not insoluble fiber cellulose, promoted colorectal tumorigenesis in AOM-treated and Apc[min/+] mice. Soluble fiber induced gut dysbiosis with Bacteroides uniformis enrichment and Bifidobacterium pseudolongum depletion, accompanied by increased fecal butyrate and serum bile acids and decreased inosine. We also identified a positive correlation between inulin dosage and colorectal tumorigenesis. Moreover, transplanting stools from mice fed with high-inulin diet increased colonic cell proliferation and oncogene expressions in germ-free mice.<br><br>CONCLUSION: High-dose soluble but not insoluble fiber potentiates colorectal tumorigenesis in a dose-dependent manner by dysregulating gut microbiota and metabolites in mice.}, }
@article {pmid37858192, year = {2023}, author = {Zhong, HJ and Xie, X and Chen, WJ and Zhuang, YP and Hu, X and Cai, YL and Zeng, HL and Xiao, C and Li, Y and Ding, Y and Xue, L and Chen, M and Zhang, J and Wu, Q and He, XX}, title = {Washed microbiota transplantation improves renal function in patients with renal dysfunction: a retrospective cohort study.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {740}, pmid = {37858192}, issn = {1479-5876}, mesh = {Humans ; Retrospective Studies ; Kidney/metabolism ; *Renal Insufficiency, Chronic/therapy ; *Gastrointestinal Microbiome ; *Microbiota ; }, abstract = {BACKGROUND: Changes in the gut microbiota composition is a hallmark of chronic kidney disease (CKD), and interventions targeting the gut microbiota present a potent approach for CKD treatment. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a modified faecal microbiota transplantation method, on the renal activity of patients with renal dysfunction.<br><br>METHODS: A comparative analysis of gut microbiota profiles was conducted in patients with renal dysfunction and healthy controls. Furthermore, the efficacy of WMT on renal parameters in patients with renal dysfunction was evaluated, and the changes in gut microbiota and urinary metabolites after WMT treatment were analysed.<br><br>RESULTS: Principal coordinate analysis revealed a significant difference in microbial community structure between patients with renal dysfunction and healthy controls (P&#x2009;=&#x2009;0.01). Patients with renal dysfunction who underwent WMT exhibited significant improvement in serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen (all P&#x2009;<&#x2009;0.05) compared with those who did not undergo WMT. The incidence of adverse events associated with WMT treatment was low (2.91%). After WMT, the Shannon index of gut microbiota and the abundance of several probiotic bacteria significantly increased in patients with renal dysfunction, aligning their gut microbiome profiles more closely with those of healthy donors (all P&#x2009;<&#x2009;0.05). Additionally, the urine of patients after WMT demonstrated relatively higher levels of three toxic metabolites, namely hippuric acid, cinnamoylglycine, and indole (all P&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: WMT is a safe and effective method for improving renal function in patients with renal dysfunction by modulating the gut microbiota and promoting toxic metabolite excretion.}, }
@article {pmid37857731, year = {2023}, author = {Bahar Halpern, K and Korem Kohanim, Y and Biram, A and Harnik, Y and Egozi, A and Yakubovsky, O and Shulman, Z and Itzkovitz, S}, title = {The cellular states and fates of shed intestinal cells.}, journal = {Nature metabolism}, volume = {5}, number = {11}, pages = {1858-1869}, pmid = {37857731}, issn = {2522-5812}, mesh = {Male ; Mice ; Animals ; *Colitis/chemically induced ; Intestinal Mucosa ; Epithelial Cells ; }, abstract = {The intestinal epithelium is replaced every few days[1]. Enterocytes are shed into the gut lumen predominantly from the tips of villi[2,3] and have been believed to rapidly die upon their dissociation from the tissue[4,5]. However, technical limitations prohibited studying the cellular states and fates of shed intestinal cells. Here we show that shed epithelial cells remain viable and upregulate distinct anti-microbial programmes upon shedding, using bulk and single-cell RNA sequencing of male mouse intestinal faecal washes. We further identify abundant shedding of immune cells, which is elevated in mice with dextran sulfate sodium-induced colitis. We find that faecal host transcriptomics reflect changes in the intestinal tissue following perturbations. Our study suggests potential functions of shed cells in the intestinal lumen and demonstrates that host cell transcriptomes in intestinal washes can be used to probe tissue states.}, }
@article {pmid37857710, year = {2023}, author = {Riwes, MM and Golob, JL and Magenau, J and Shan, M and Dick, G and Braun, T and Schmidt, TM and Pawarode, A and Anand, S and Ghosh, M and Maciejewski, J and King, D and Choi, S and Yanik, G and Geer, M and Hillman, E and Lyssiotis, CA and Tewari, M and Reddy, P}, title = {Feasibility of a dietary intervention to modify gut microbial metabolism in patients with hematopoietic stem cell transplantation.}, journal = {Nature medicine}, volume = {29}, number = {11}, pages = {2805-2813}, pmid = {37857710}, issn = {1546-170X}, support = {P01 HL149633/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Humans ; Butyrates ; Feasibility Studies ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/prevention &amp; control ; *Hematopoietic Stem Cell Transplantation/methods ; }, abstract = {Evaluation of the impact of dietary intervention on gastrointestinal microbiota and metabolites after allogeneic hematopoietic stem cell transplantation (HCT) is lacking. We conducted a feasibility study as the first of a two-phase trial. Ten adults received resistant potato starch (RPS) daily from day -7 to day 100. The primary objective was to test the feasibility of RPS and its effect on intestinal microbiome and metabolites, including the short-chain fatty acid butyrate. Feasibility met the preset goal of 60% or more, adhering to 70% or more doses; fecal butyrate levels were significantly higher when participants were on RPS than when they were not (P < 0.0001). An exploratory objective was to evaluate plasma metabolites. We observed longitudinal changes in plasma metabolites compared to baseline, which were independent of RPS (P < 0.0001). However, in recipients of RPS, the dominant plasma metabolites were more stable compared to historical controls with significant difference at engraftment (P < 0.05). These results indicate that RPS in recipients of allogeneic HCT is feasible; in this study, it was associated with significant alterations in intestinal and plasma metabolites. A phase 2 trial examining the effect of RPS on graft-versus-host disease in recipients of allogeneic HCT is underway. ClinicalTrials.gov registration: NCT02763033 .}, }
@article {pmid37857552, year = {2023}, author = {Chen, Z and Lv, M and Liang, J and Yang, K and Li, F and Zhou, Z and Qiu, M and Chen, H and Cai, Z and Cui, W and Li, Z}, title = {Neuropeptide Y-Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {10}, number = {33}, pages = {e2303015}, pmid = {37857552}, issn = {2198-3844}, support = {81871090//National Natural Science Foundation of China/ ; 32171340//National Natural Science Foundation of China/ ; 32101104//National Natural Science Foundation of China/ ; 2020YFA0908200//National Key Research and Development Program of China/ ; 202140127//Shanghai Municipal Health Planning Commission/ ; }, mesh = {Female ; Humans ; Rats ; Animals ; Neuropeptide Y/metabolism ; *Osteoporosis, Postmenopausal ; *Gastrointestinal Microbiome ; Lipopolysaccharides ; Hypothalamus/metabolism ; }, abstract = {Postmenopausal osteoporosis (PMO) is often accompanied by neuroendocrine changes in the hypothalamus, which closely associates with the microbial diversity, community composition, and intestinal metabolites of gut microbiota (GM). With the emerging role of GM in bone metabolism, a potential neuroendocrine signal neuropeptide Y (NPY) mediated brain-gut-bone axis has come to light. Herein, it is reported that exogenous overexpression of NPY reduced bone formation, damaged bone microstructure, and up-regulated the expressions of pyroptosis-related proteins in subchondral cancellous bone in ovariectomized (OVX) rats, but Y1 receptor antagonist (Y1Ra) reversed these changes. In addition, it is found that exogenous overexpression of NPY aggravated colonic inflammation, impaired intestinal barrier integrity, enhanced intestinal permeability, and increased serum lipopolysaccharide (LPS) in OVX rats, and Y1Ra also reversed these changes. Most importantly, NPY and Y1Ra modulated the microbial diversity and changed the community composition of GM in OVX rats, and thereby affecting the metabolites of GM (e.g., LPS) entering the blood circulation. Moreover, fecal microbiota transplantation further testified the effect of NPY-mediated GM changes on bone. In vitro, LPS induced pyroptosis, reduced viability, and inhibited differentiation of osteoblasts. The study demonstrated the existence of NPY-mediated brain-gut-bone axis and it might be a novel emerging target to treat PMO.}, }
@article {pmid37856155, year = {2023}, author = {Cheng, J and Liu, D and Huang, Y and Chen, L and Li, Y and Yang, Z and Fu, S and Hu, G}, title = {Phlorizin Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Gut Microbiota and Inhibiting Ferroptosis.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {43}, pages = {16043-16056}, doi = {10.1021/acs.jafc.3c01497}, pmid = {37856155}, issn = {1520-5118}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Phlorhizin ; Dextran Sulfate/adverse effects ; *Ferroptosis ; *Colitis/chemically induced/drug therapy ; *Colitis, Ulcerative/chemically induced/drug therapy ; Colon ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {Phlorizin (PHZ) is the main active component of apple peel and presents a potential application value. In the past few years, some reports have suggested that PHZ may have antioxidant and anti-inflammatory effects. Herein, we have attempted to assess the protective effects of PHZ on dextran sodium sulfate (DSS)-induced colitis in mice and to determine the underlying molecular mechanisms. Our results suggested that early intervention with PHZ (20, 40, and 80 mg/kg) significantly reduced the severity of DSS-induced colitis in mice, as presented by a longer colon, improved tight junction protein, decreased disease activity index, and attenuated inflammatory factors. Additionally, early intervention with + (20, 40, and 80 mg/kg) significantly inhibited ferroptosis by decreasing the surrogate ferroptosis marker levels (MDA and Iron Content). Additionally, PHZ (80 mg/kg) increased the diversity of intestinal flora in colitic mice by elevating the levels of beneficial bacteria (Lactobacillaceae and Muribaculaceae) and reducing the levels of harmful bacteria (Lachnospiraceae). This indirectly led to an increase in the amount of short-chain fatty acids. A fecal microbial transplantation (FMT) test was conducted to show that PHZ (80 mg/kg) ameliorated ulcerative colitis (UC) by regulating gut dysbiosis. In conclusion, early intervention with PHZ decreased DSS-induced colitis in mice by preserving their intestinal barrier and regulating their intestinal flora.}, }
@article {pmid37854336, year = {2023}, author = {Guo, C and Zhang, P and Li, J and Zhou, C and Yang, Z and Zhang, Y and Luo, Y and Zhou, J and Cai, Y and Ming, Y}, title = {The characteristics of intestinal microbiota in patients with chronic schistosomiasis japonica-induced liver fibrosis by 16S rRNA gene sequence.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1276404}, pmid = {37854336}, issn = {1664-302X}, abstract = {BACKGROUND: The intestinal microbiota is known to play a role in the development of liver disease, there is a limited understanding of the intestinal microbiota associated with chronic schistosomiasis japonica. This study sought to explore the characteristics of the intestinal microbiota in patients with chronic schistosomiasis japonica and identify potential biomarkers that could aid diagnosis.<br><br>METHODS: A total of 40 residents of Qingshan Island in Yueyang (Hunan, China) were enrolled in this cross-sectional study. These individuals were divided into two groups for analysis of the intestinal microbiota: patients with chronic schistosomiasis japonica-induced liver fibrosis group (CSJ group, n = 10) and a healthy control group (HC group, n = 30). Feces were collected from each participant and analyzed by 16S rRNA gene sequencing, which included species composition analysis at the phylum and family levels, &#x3b1; and &#x3b2; diversity analysis, LEfSe, Kyoto Encyclopedia of Genes and Genome (KEGG) and Clusters of Orthologous Groups of proteins (COG) analysis.<br><br>RESULTS: Our results indicated that Schistosoma japonicum infection changed the composition and abundance of intestinal microbiota at the phylum and family levels. Compared with the HC group, the &#x3b1; and &#x3b2; diversity results showed that CSJ group had low diversity of species of the intestinal microbiome. LEfSe and relative abundance analysis found that the Prevotella 7, Alloprevotella, and Holdemanella genera were significantly higher in the CSJ group than in the HC group. Meanwhile, the ROC analysis showed that the area under the curve (AUC) of Prevotella 7, Alloprevotella, and Holdemanella genera was 0.779, 0.769, and 0.840, respectively. KEGG and COG analysis showed that the Replication and Repair, and Defense Mechanism pathways correlated strongly with chronic schistosomiasis japonica infection.<br><br>CONCLUSION: The current study was the first to explore differences in the intestinal microbiota of patients with chronic schistosomiasis japonica-induced liver fibrosis and healthy people from Qingshan Island, which indicated that Prevotella 7, Alloprevotella, and Holdemanella genera could have a potential value in non-invasive diagnosis of chronic schistosomiasis japonica-induced fibrosis.}, }
@article {pmid37852131, year = {2023}, author = {Fang, G and Wang, S and Chen, Q and Luo, H and Lian, X and Shi, D}, title = {Time-restricted feeding affects the fecal microbiome metabolome and its diurnal oscillations in lung cancer mice.}, journal = {Neoplasia (New York, N.Y.)}, volume = {45}, number = {}, pages = {100943}, pmid = {37852131}, issn = {1476-5586}, mesh = {Mice ; Animals ; Mice, Nude ; *Lung Neoplasms ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; *Microbiota ; Feces ; Metabolome ; Urethane ; }, abstract = {The homeostasis of the gut microbiota and circadian rhythm is critical to host health, and both are inextricably intertwined with lung cancer. Although time-restricted feeding (TRF) can maintain circadian synchronization and improve metabolic disorders, the effects of TRF on the fecal microbiome, metabolome and their diurnal oscillations in lung cancer have not been discussed. We performed 16S rRNA sequencing and untargeted metabonomic sequencing of the feces prepared from models of tumor-bearing BALB/c nude mice and urethane-induced lung cancer. We demonstrated for the first time that TRF significantly delayed the growth of lung tumors. Moreover, TRF altered the abundances of the fecal microbiome, metabolome and circadian clocks, as well as their rhythmicity, in lung cancer models of tumor-bearing BALB/c nude mice and/or urethane-induced lung cancer C57BL/6J mice. The results of fecal microbiota transplantation proved that the antitumor effects of TRF occur by regulating the fecal microbiota. Notably, Lactobacillus and Bacillus were increased upon TRF and were correlated with most differential metabolites. Pathway enrichment analysis of metabolites revealed that TRF mainly affected immune and inflammatory processes, which might further explain how TRF exerted its anticancer benefits. These findings underscore the possibility that the fecal microbiome/metabolome regulates lung cancer following a TRF paradigm.}, }
@article {pmid37851840, year = {2023}, author = {Zhang, Z and Cheng, N and Liang, J and Deng, Y and Xiang, P and Hei, Z and Li, X}, title = {Gut microbiota changes in animal models of spinal cord injury: a preclinical systematic review and meta-analysis.}, journal = {Annals of medicine}, volume = {55}, number = {2}, pages = {2269379}, pmid = {37851840}, issn = {1365-2060}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *Microbiota ; Fecal Microbiota Transplantation ; Models, Animal ; Bacteria ; *Spinal Cord Injuries ; }, abstract = {BACKGROUND: An increasing number of studies show that the intestinal flora is closely related to spinal cord injury. Many researchers are exploring the changes in the richness, diversity, and evenness of intestinal flora in spinal cord injury animal models to identify the characteristic bacteria.<br><br>METHODS: A comprehensive literature search was conducted using three databases: PubMed, Embase, and Web of Science. A meta-analysis was performed using R 4.3.1 to evaluate the comparison of microbiota diversity, richness, and evenness and the relative abundance of intestinal microbiota in animals with spinal cord injury and blank controls.<br><br>RESULTS: Fifteen studies were included in the meta-analysis, of which 12 involved gut microbiota distribution indicators and 11 included intestinal microflora relative abundance indicators. Meta-analysis of high-dimensional indicators describing the distribution of the gut microbiota identified a substantial decline in the evenness and richness of the intestinal flora. In addition, the Actinobacteria phylum and Erysipelotrichales and Clostridiales orders were significantly different between the spinal cord injury and sham groups; therefore, they may be the characteristic bacteria in spinal cord injury models.<br><br>CONCLUSION: Our meta-analysis suggested that the gut microbiota in the spinal cord injury animal model group was altered compared with that in the control group, with varying degrees of changes in richness and evenness and potentially pathogenic characteristic flora. More rigorous methodological studies are needed because of the high heterogeneity and limited sample size. Further research is needed to clinically apply intestinal microbiota and potentially guide fecal microbiota transplantation therapy.}, }
@article {pmid37851313, year = {2024}, author = {Pan, I and Issac, PK and Rahman, MM and Guru, A and Arockiaraj, J}, title = {Gut-Brain Axis a Key Player to Control Gut Dysbiosis in Neurological Diseases.}, journal = {Molecular neurobiology}, volume = {61}, number = {12}, pages = {9873-9891}, pmid = {37851313}, issn = {1559-1182}, mesh = {Humans ; *Dysbiosis ; *Gastrointestinal Microbiome/physiology ; *Brain-Gut Axis/physiology ; Animals ; *Nervous System Diseases/microbiology/physiopathology ; Brain/metabolism ; Parkinson Disease/microbiology/therapy ; }, abstract = {Parkinson's disease is a chronic neuropathy characterised by the formation of Lewy bodies (misfolded alpha-synuclein) in dopaminergic neurons of the substantia nigra and other parts of the brain. Dopaminergic neurons play a vital role in generating both motor and non-motor symptoms. Finding therapeutic targets for Parkinson's disease (PD) is hindered due to an incomplete understanding of the disease's pathophysiology. Existing evidence suggests that the gut microbiota participates in the pathogenesis of PD via immunological, neuroendocrine, and direct neural mechanisms. Gut microbial dysbiosis triggers the loss of dopaminergic neurons via mitochondrial dysfunction. Gut dysbiosis triggers bacterial overgrowth in the small intestine, which increases the permeability barrier and induces systemic inflammation. It results in excessive stimulation of the innate immune system. In addition to that, activation of enteric neurons and enteric glial cells initiates the aggregation of alpha-synuclein. This alpha-synucleinopathy thus affects all levels of the brain-gut axis, including the central, autonomic, and enteric nervous systems. Though the neurobiological signaling cascade between the gut microbiome and the central nervous system is poorly understood, gut microbial metabolites may serve as a promising therapeutic strategy for PD. This article summarises all the known possible ways of bidirectional signal communication, i.e., the "gut-brain axis," where microbes from the middle gut interact with the brain and vice versa, and highlights a unique way to treat neurodegenerative diseases by maintaining homeostasis. The tenth cranial nerve (vagus nerve) plays a significant part in this signal communication. However, the leading regulatory factor for this axis is a diet that helps with microbial colonisation and brain function. Short-chain fatty acids (SCFAs), derived from microbially fermented dietary fibres, link host nutrition to maintain intestinal homeostasis. In addition to that, probiotics modulate cognitive function and the metabolic and behavioural conditions of the body. As technology advances, new techniques will emerge to study the tie-up between gut microbes and neuronal diseases.}, }
@article {pmid37849493, year = {2023}, author = {Lan, KY and Le, PH and Chiu, CT and Chen, CC and Yeh, YM and Cheng, HT and Kuo, CJ and Chen, CL and Chen, YC and Yeh, PJ and Chiu, CH and Chang, CJ}, title = {Fecal microbiota transplantation for treatment of refractory or recurrent Clostridioides difficile infection in Taiwan: a cost-effectiveness analysis.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1229148}, pmid = {37849493}, issn = {2296-858X}, abstract = {BACKGROUND: Compared to antibiotic treatment, fecal microbiota transplantation (FMT) is a more effective treatment for refractory or recurrent CDI (rCDI). Patients with inflammatory bowel disease (IBD) have a higher incidence of CDI and worse outcomes. There has been no study from Asia to evaluate the cost-effectiveness of FMT for overall rCDI patients and rCDI patients with IBD.<br><br>METHODS: We applied a Markov model with deterministic and probabilistic sensitivity analyses to evaluate the cost and effectiveness of different treatments for rCDI patients with a time horizon of 1 year from the payer's perspective. We compared the cost and clinical outcomes of FMT through colonoscopy to two antibiotics (vancomycin and fidaxomicin) using data from Chang Gung Memorial Hospital, Taoyuan, Taiwan.<br><br>RESULTS: Compared to vancomycin, FMT was cost-effective in overall rCDI patients as well as IBD patients with rCDI [USD 39356 (NT$1,101,971.98)/quality-adjusted life year (QALY) gained in overall patients; USD65490 (NT$1,833,719.14)/QALY gained in IBD patients]. Compared to fidaxomicin, FMT was only cost-effective in overall rCDI patients [USD20255 (NT$567,133.45)/QALY gained] but slightly increased QALY (0.0018 QALY gained) in IBD patients with rCDI.<br><br>CONCLUSION: FMT is cost-effective, compared to vancomycin or fidaxomicin, for the treatment of rCDI in most scenarios from the payers' perspective in Taiwan.}, }
@article {pmid37849266, year = {2023}, author = {Cui, JQ and Tian, HL and Wang, XJ and Wang, L and Liu, YK and Ye, C and Ding, LF and Li, N and Chen, QY}, title = {[Analysis of short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {26}, number = {10}, pages = {955-962}, doi = {10.3760/cma.j.cn441530-20230816-00052}, pmid = {37849266}, issn = {1671-0274}, support = {202240177//Shanghai Health Commission's Surface Project/ ; }, mesh = {Female ; Humans ; Male ; Middle Aged ; Abdominal Pain/complications ; China ; Diarrhea ; *Enteritis/etiology/therapy ; *Fecal Microbiota Transplantation/methods ; Flatulence/complications ; Hemoglobins ; *Intestinal Obstruction/etiology/surgery ; *Nutritional Support ; Postoperative Complications ; Prealbumin ; Prospective Studies ; Quality of Life ; Retrospective Studies ; Treatment Outcome ; Adult ; *Radiotherapy/adverse effects ; }, abstract = {Objective: To explore the short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction. Methods: The cohort of this prospective cohort study comprised 45 patients (nine men and 36 women) with radiation-induced enteritis complicated by intestinal obstruction admitted to Shanghai Tenth People's Hospital Affiliated to Tongji University from January 2022 to October 2022. The median age was 53 (42-65) years. Thirty-five of the patients had gynecological tumors and 10 colorectal malignancies. The patients were randomly allocated to a fecal microbiota transplantation group of 20 patients who underwent fecal microbiota transplantation starting 2 weeks before surgery for 6 days, in addition to receiving conventional perioperative treatment, and a conventional treatment group of 25 patients who only received nutritional support during the perioperative period. There were no significant differences in baseline characteristics (sex, age, preoperative nutritional indices, and surgical procedure) between the two groups (all P>0.05). Postoperative recovery (time to passing flatus or a bowel movement, length of stay) and complications were compared between the two groups. Postoperative complications within 30 days after surgery classified in accordance with the international Clavien-Dindo classification of surgical complications (I-V) were statistically analyzed. Improvement in gastrointestinal symptoms, namely abdominal pain, distension, diarrhea, and rectal bleeding) and gastrointestinal quality of life scores (which include 36 problems rated 0-144 points related to physical, psychological, social activities and family life; the lower the score, the more severe the symptoms) were compared between the two groups. Nutritional recovery was assessed by body mass, body mass index, total protein, albumin, prealbumin, and hemoglobin. Results: Compared with the conventional treatment group, the postoperative hospital stay was shorter in the fecal microbiota transplantation group (8.0±4.3 days vs. 11.2±5.4 days, t=2.157, P=0.037) and the time to passage of flatus or having a bowel movement was earlier (2.2±3.2 days vs. 3.9±2.3 days, t=2.072, P=0.044). There were 26 postoperative complications in the fecal microbiota transplantation group and 59 in the conventional treatment group. There were 20 and 36 Grade I to II complications and no and three Grade III to V complications in the transplantation and conventional treatment group, respectively. The overall grade of complication did not differ significantly between the two groups (P=0.544). However, the incidence of postoperative intestinal inflammatory obstruction was lower in the fecal microbiota transplantation than the conventional treatment group (10.0% [2/20] vs. 40.0% [10/25], P=0.040). One patient in the conventional treatment group died. This patient had complete intestinal obstruction complicated by severe malnutrition preoperatively, and an intestinal fistula complicated by abdominal infection postoperatively, and died despite active treatment. Nineteen and 23 patients in the transplantation and conventional treatment group, respectively, attended for follow-up 1 month after surgery; 19 and 21, respectively, attended for follow-up 3 months after surgery, and 17 and 20, respectively, attended for follow-up 6 months after surgery. There were no significant differences between the two groups in abdominal pain or rectal bleeding 1, 3, or 6 months after surgery (all P>0.05). One month after surgery, the incidence of abdominal distension and diarrhea was lower in the fecal microbiota transplantation than in the conventional treatment group (3/19 vs. 48.0% [11/23], P=0.048; 3/19 vs. 52.2% [12/23], P=0.023). However, at the 3 and 6 month follow-ups the incidence of abdominal distension and diarrhea had gradually decreased in both groups and the differences between the groups were not statistically significant (P>0.05 for all). Scores for gastrointestinal quality of life improved significantly in both treatment groups compared with preoperative values (F=71.250, P<0.001; F=79.130, P<0.001, respectively). Scores for gastrointestinal quality of life were higher in the fecal microbiota transplantation than the conventional treatment group at all follow-up time points (P<0.05). One-way ANOVA showed that body mass, body mass index, and total protein, albumin and hemoglobin concentrations improved in both groups compared with preoperative values (all P<0.05). Prealbumin concentration improved significantly in the transplantation (F=5.514, P=0.002), but not in the conventional, group (F=1.535, P=0.211). The improvements in body mass, body mass index, total protein, and albumin were better in the fecal microbiota transplantation than conventional treatment group at 3 and 6 months of follow-up (all P<0.05). Conclusion: Perioperative fecal microbiota transplantation combined with nutritional support is effective in improving early postoperative nutritional status and quality of life in patients with radiation-induced enteritis complicated by intestinal obstruction.}, }
@article {pmid37849234, year = {2023}, author = {Grabrucker, S and Marizzoni, M and Silajdžić, E and Lopizzo, N and Mombelli, E and Nicolas, S and Dohm-Hansen, S and Scassellati, C and Moretti, DV and Rosa, M and Hoffmann, K and Cryan, JF and O'Leary, OF and English, JA and Lavelle, A and O'Neill, C and Thuret, S and Cattaneo, A and Nolan, YM}, title = {Microbiota from Alzheimer's patients induce deficits in cognition and hippocampal neurogenesis.}, journal = {Brain : a journal of neurology}, volume = {146}, number = {12}, pages = {4916-4934}, pmid = {37849234}, issn = {1460-2156}, support = {MR/S00484X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Rats ; Animals ; *Alzheimer Disease ; Hippocampus ; Cognition ; *Gastrointestinal Microbiome/physiology ; Neurogenesis/physiology ; }, abstract = {Alzheimer's disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer's disease by showing specific alterations in the gut microbiome composition of Alzheimer's patients and in rodent models. However, it is unknown whether gut microbiota alterations are causal in the manifestation of Alzheimer's symptoms. To understand the involvement of Alzheimer's patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer's patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer's patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer's systemic environment on proxy neurogenesis readouts. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera. Our findings reveal for the first time, that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer's disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer's.}, }
@article {pmid37846600, year = {2024}, author = {Li, Y and Liu, Q and Zhang, L and Zou, J and He, R and Zhou, Y and Qian, C and Zhu, Y and Chen, R and Zhang, Y and Cai, P and Wang, M and Shao, W and Ji, M and Wu, H and Zhang, F and Liu, Z and Liu, Y}, title = {Washed microbiota transplantation reduces glycemic variability in unstable diabetes.}, journal = {Journal of diabetes}, volume = {16}, number = {2}, pages = {e13485}, pmid = {37846600}, issn = {1753-0407}, support = {2022YFA0806103//National Key R&amp;D Program of China/ ; 81770778//National Natural Science Foundation of China/ ; 81800724//National Natural Science Foundation of China/ ; 81800735//National Natural Science Foundation of China/ ; 82070849//National Natural Science Foundation of China/ ; 82270871//National Natural Science Foundation of China/ ; BK20180672//Natural Science Foundation of Jiangsu Province/ ; 18KJB310005//Natural Science Foundation of the Jiangsu Higher Education Institutions/ ; BE2022794//the Jiangsu Provincial Key Research Development Program/ ; }, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; *Diabetes Mellitus/therapy ; Insulin ; *Gastrointestinal Microbiome/genetics ; Glucose ; }, abstract = {BACKGROUND: Dysbiosis of gut microbiota is causally linked to impaired host glucose metabolism. We aimed to study effects of the new method of fecal microbiota transplantation, washed microbiota transplantation (WMT), on reducing glycemic variability (GV) in unstable diabetes.<br><br>METHODS: Fourteen eligible patients received three allogenic WMTs and were followed up at 1&#x2009;week, 1&#x2009;month, and 3&#x2009;months. Primary outcomes were daily insulin dose, glucose excursions during meal tests, and GV indices calculated from continuous monitoring or self-monitoring glucose values. Secondary outcomes were multiomics data, including 16S rRNA gene sequencing, metagenomics, and metabolomics to explore underlying mechanisms.<br><br>RESULTS: Daily insulin dose and glucose excursions markedly dropped, whereas GV indices significantly improved up to 1&#x2009;month. WMT increased gut microbial alpha diversity, beta diversity, and network complexity. Taxonomic changes featured lower abundance of genera Bacteroides and Escherichia-Shigella, and higher abundance of genus Prevotella. Metagenomics functional annotations revealed enrichment of distinct microbial metabolic pathways, including methane biosynthesis, citrate cycle, amino acid degradation, and butyrate production. Derived metabolites correlated significantly with improved GV indices. WMT did not change circulating inflammatory cytokines, enteroendocrine hormones, or C-peptide.<br><br>CONCLUSIONS: WMT showed strong ameliorating effect on GV, raising the possibility of targeting gut microbiota as an effective regimen to reduce GV in diabetes.}, }
@article {pmid37842639, year = {2023}, author = {Patra, D and Banerjee, D and Ramprasad, P and Roy, S and Pal, D and Dasgupta, S}, title = {Recent insights of obesity-induced gut and adipose tissue dysbiosis in type 2 diabetes.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1224982}, pmid = {37842639}, issn = {2296-889X}, abstract = {An imbalance in microbial homeostasis, referred to as dysbiosis, is critically associated with the progression of obesity-induced metabolic disorders including type 2 diabetes (T2D). Alteration in gut microbial diversity and the abundance of pathogenic bacteria disrupt metabolic homeostasis and potentiate chronic inflammation, due to intestinal leakage or release of a diverse range of microbial metabolites. The obesity-associated shifts in gut microbial diversity worsen the triglyceride and cholesterol level that regulates adipogenesis, lipolysis, and fatty acid oxidation. Moreover, an intricate interaction of the gut-brain axis coupled with the altered microbiome profile and microbiome-derived metabolites disrupt bidirectional communication for instigating insulin resistance. Furthermore, a distinct microbial community within visceral adipose tissue is associated with its dysfunction in obese T2D individuals. The specific bacterial signature was found in the mesenteric adipose tissue of T2D patients. Recently, it has been shown that in Crohn's disease, the gut-derived bacterium Clostridium innocuum translocated to the mesenteric adipose tissue and modulates its function by inducing M2 macrophage polarization, increasing adipogenesis, and promoting microbial surveillance. Considering these facts, modulation of microbiota in the gut and adipose tissue could serve as one of the contemporary approaches to manage T2D by using prebiotics, probiotics, or faecal microbial transplantation. Altogether, this review consolidates the current knowledge on gut and adipose tissue dysbiosis and its role in the development and progression of obesity-induced T2D. It emphasizes the significance of the gut microbiota and its metabolites as well as the alteration of adipose tissue microbiome profile for promoting adipose tissue dysfunction, and identifying novel therapeutic strategies, providing valuable insights and directions for future research and potential clinical interventions.}, }
@article {pmid37842346, year = {2023}, author = {Warraich, F and Sohail, SH and Knee, A and Smith, J and Schlecht, H and Skiest, D}, title = {Factors Associated With Fecal Microbiota Transplant Failure in the Treatment of Recurrent Clostridioides difficile Infection: A Single-Center Retrospective Study.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e45118}, pmid = {37842346}, issn = {2168-8184}, abstract = {Background Clostridioides difficile infection (CDI) is a major cause of hospital-acquired diarrhea and is associated with substantial morbidity and mortality. Recurrences following treatment are common. Fecal microbiota transplantation (FMT) is a therapeutic intervention in which stool from a healthy donor is administered to a patient with recurrent CDI. Studies to date of predictors of FMT failure have primarily included inpatients. In this study, we aimed to describe FMT failure rates within one year of FMT and evaluate factors associated with FMT failure. Methodology We conducted an exploratory retrospective study of consecutive patients who underwent outpatient FMT at a single tertiary care center in Western Massachusetts from December 2014 through September 2018. We collected patient data including demographics, CDI-related factors, and FMT-related factors. FMT failure was defined as non-response or recurrence of diarrhea, associated with positive stool C. difficile toxin or polymerase chain reaction. Unadjusted relative risk (RR) and 95% confidence intervals for factors associated with FMT failure were estimated using log-binomial regression. Results A total of 92 patients were included with a mean age of 64 years. CDI severity was mild or moderate in 73% and severe or fulminant in 27%. The most common FMT indication was recurrent CDI in 76% of patients. FMT failure occurred in 25 of 92 (27%) patients, with half occurring within 11 days. Factors associated with FMT failure were active malignancy (RR = 2.56), prior hospitalizations (RR = 2.42), and receipt of non-CDI antibiotics within six months of FMT (RR = 2.80). We did not observe strong associations for risk of FMT failure with age ≥65, sex, use of proton pump inhibitors or H2 receptor agonists, history of colectomy, immunosuppression, history of malignancy, diabetes, appendectomy, CDI severity, or probiotic use. Conclusions Active malignancy, prior CDI hospitalizations, and non-CDI antibiotics within six months before FMT were associated with FMT failure in the outpatient setting. Knowledge of the above factors may help inform shared decision-making with patients at risk for FMT failure.}, }
@article {pmid37842104, year = {2023}, author = {Quattrini, C and Bozorgmanesh, R and Egli, P and Magdesian, KG}, title = {Fecal microbiota transplant for treatment of diarrhea in adult hospitalized horses-111 cases (2013-2018).}, journal = {Open veterinary journal}, volume = {13}, number = {9}, pages = {1135-1140}, pmid = {37842104}, issn = {2218-6050}, mesh = {Horses ; Animals ; Fecal Microbiota Transplantation/veterinary ; Retrospective Studies ; Case-Control Studies ; Prospective Studies ; Treatment Outcome ; Diarrhea/therapy/veterinary ; *Colitis/therapy/veterinary ; *Horse Diseases/therapy ; }, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) is increasingly administered as part of the treatment of colitis in horses, yet there is little data as to its effectiveness.<br><br>AIM: Retrospective evaluation of the effects of FMT on discharge status, fecal consistency, length of hospitalization, and improvement in clinical signs in horses hospitalized for diarrhea.<br><br>METHODS: Retrospective case-control study. Medical records of adult horses (>1 year old) that received at least one transfaunation treatment (2013-2018) in two referral hospitals were identified through a medical records database search. Medical records of contemporary adult horses with diarrhea who did not receive FMT at the same study centers were used as controls.<br><br>RESULTS: Control horses had statistically significant shorter hospitalization [7 (1-21)] as compared to the transfaunation group [12 (3-31)] (p = 0.0006). There were no significant differences between groups in the number of days to the improvement of feces (p = 0.38), or in days to normalization of fecal consistency (p = 0.43), respiratory rate (p = 0.42), heart rate (p = 0.27), body temperature (p = 0.12), peripheral white blood cell count (p = 0.37), improvement in appetite (p = 0.81), or attitude (p = 0.06). There was also no significant difference in survival to discharge (transfaunation 28/37, 75.7%; control 56/74, 75.7%, p = 1.0).<br><br>CONCLUSION: There were no significant advantages of performing FMTs in horses with diarrhea in this retrospective study. This highlights the need for prospective, randomized studies to evaluate the efficacy of FMT, as well as different formulations, in horses with colitis before this can become standard practice.}, }
@article {pmid37841750, year = {2023}, author = {Huang, J and Gong, C and Zhou, A}, title = {Modulation of gut microbiota: a novel approach to enhancing the effects of immune checkpoint inhibitors.}, journal = {Therapeutic advances in medical oncology}, volume = {15}, number = {}, pages = {17588359231204854}, pmid = {37841750}, issn = {1758-8340}, abstract = {Although immune checkpoint inhibitors (ICIs) have greatly improved the prognosis of some cancer patients, the majority still fail to respond adequately, and the available biomarkers cannot reliably predict drug efficacy. The gut microbiota has received widespread attention among the various intrinsic and extrinsic factors contributing to drug resistance. As an essential regulator of physiological function, the impact of gut microbiota on host immunity and response to cancer therapy is increasingly recognized. Several studies have demonstrated significant differences in gut microbiota between responders and nonresponders. The gut microbiota associated with better clinical outcomes is called 'favorable gut microbiota'. Significantly, interventions can alter the gut microbiota. By shifting the gut microbiota to the 'favorable' one through various modifications, preclinical and clinical studies have yielded more pronounced responses and better clinical outcomes when combined with ICIs treatment, providing novel approaches to improve the efficacy of cancer immunotherapy. These findings may be attributed to the effects of gut microbiota and its metabolites on the immune microenvironment and the systemic immune system, but the underlying mechanisms remain to be discovered. In this review, we summarize the clinical evidence that the gut microbiota is strongly associated with the outcomes of ICI treatment and describe the gut microbiota characteristics associated with better clinical outcomes. We then expand on the current prevalent modalities of gut microbiota regulation, provide a comprehensive overview of preclinical and clinical research advances in improving the therapeutic efficacy and prognosis of ICIs by modulating gut microbiota, and suggest fundamental questions we need to address and potential directions for future research expansion.}, }
@article {pmid37841685, year = {2023}, author = {Fagan, MM and Welch, CB and Scheulin, KM and Sneed, SE and Jeon, JH and Golan, ME and Cheek, SR and Barany, DA and Oeltzschner, G and Callaway, TR and Zhao, Q and Park, HJ and Lourenco, JM and Duberstein, KJ and West, FD}, title = {Fecal microbial transplantation limits neural injury severity and functional deficits in a pediatric piglet traumatic brain injury model.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1249539}, pmid = {37841685}, issn = {1662-4548}, abstract = {Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. Due to bidirectional communication between the brain and gut microbial population, introduction of key gut bacteria may mitigate critical TBI-induced secondary injury cascades, thus lessening neural damage and improving functional outcomes. The objective of this study was to determine the efficacy of a daily fecal microbial transplant (FMT) to alleviate neural injury severity, prevent gut dysbiosis, and improve functional recovery post TBI in a translational pediatric piglet model. Male piglets at 4-weeks of age were randomly assigned to Sham + saline, TBI + saline, or TBI + FMT treatment groups. A moderate/severe TBI was induced by controlled cortical impact and Sham pigs underwent craniectomy surgery only. FMT or saline were administered by oral gavage daily for 7 days. MRI was performed 1 day (1D) and 7 days (7D) post TBI. Fecal and cecal samples were collected for 16S rRNA gene sequencing. Ipsilateral brain and ileum tissue samples were collected for histological assessment. Gait and behavior testing were conducted at multiple timepoints. MRI showed that FMT treated animals demonstrated decreased lesion volume and hemorrhage volume at 7D post TBI as compared to 1D post TBI. Histological analysis revealed improved neuron and oligodendrocyte survival and restored ileum tissue morphology at 7D post TBI in FMT treated animals. Microbiome analysis indicated decreased dysbiosis in FMT treated animals with an increase in multiple probiotic Lactobacilli species, associated with anti-inflammatory therapeutic effects, in the cecum of the FMT treated animals, while non-treated TBI animals showed an increase in pathogenic bacteria, associated with inflammation and disease such in feces. FMT mediated enhanced cellular and tissue recovery resulted in improved motor function including stride and step length and voluntary motor activity in FMT treated animals. Here we report for the first time in a highly translatable pediatric piglet TBI model, the potential of FMT treatment to significantly limit cellular and tissue damage leading to improved functional outcomes following a TBI.}, }
@article {pmid37841431, year = {2023}, author = {Wang, Y and Han, W and Wang, N and Han, M and Ban, M and Dai, J and Dong, Y and Sun, T and Xu, J}, title = {The role of microbiota in the development and treatment of gastric cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1224669}, pmid = {37841431}, issn = {2234-943X}, abstract = {The stomach was once considered a sterile organ until the discovery of Helicobacter pylori (HP). With the application of high-throughput sequencing technology and macrogenomics, researchers have identified fungi and fivemajor bacterial phyla within the stomachs of healthy individuals. These microbial communities exert regulatory influence over various physiological functions, including energy metabolism and immune responses. HP is a well-recognized risk factor for gastric cancer, significantly altering the stomach's native microecology. Currently, numerous studies are centered on the mechanisms by which HP contributes to gastric cancer development, primarily involving the CagA oncoprotein. However, aside from exogenous infections such as HP and EBV, certain endogenous dysbiosis can also lead to gastric cancer through multiple mechanisms. Additionally, gut microbiota and its metabolites significantly impact the development of gastric cancer. The role of microbial therapies, including diet, phages, probiotics and fecal microbiota transplantation, in treating gastric cancer should not be underestimated. This review aims to study the mechanisms involved in the roles of exogenous pathogen infection and endogenous microbiota dysbiosis in the development of gastric cancer. Also, we describe the application of microbiota therapy in the treatment and prognosis of gastric cancer.}, }
@article {pmid37841129, year = {2023}, author = {Li, MY and Duan, JQ and Wang, XH and Liu, M and Yang, QY and Li, Y and Cheng, K and Liu, HQ and Wang, F}, title = {Inulin Inhibits the Inflammatory Response through Modulating Enteric Glial Cell Function in Type 2 Diabetic Mellitus Mice by Reshaping Intestinal Flora.}, journal = {ACS omega}, volume = {8}, number = {40}, pages = {36729-36743}, pmid = {37841129}, issn = {2470-1343}, abstract = {Inulin, a commonly used dietary fiber supplement, is capable of modulating the gut microbiome. Chronic inflammation resulting from metabolic abnormalities and gut flora dysfunction plays a significant role in the development of type 2 diabetes mellitus (T2DM). Our research has demonstrated that inulin administration effectively reduced colonic inflammation in T2DM mice by inducing changes in the gut microbiota and increasing the concentration of butyric acid, which in turn modulated the function of enteric glial cells (EGCs). Experiments conducted on T2DM mice revealed that inulin administration led to an increase in the Bacteroidetes/Firmicutes ratio and the concentration of butyric acid in the colon. The anti-inflammatory effects of altered gastrointestinal flora and its metabolites were further confirmed through fecal microbiota transplantation. Butyric acid was found to inhibit the activation of the κB inhibitor kinase β/nuclear factor κB pathway, regulate the expression levels of interleukin-6 and tumor necrosis factor-α, suppress the abnormal activation of EGCs, and prevent the release of inflammatory factors by EGCs. Similar results were observed in vitro experiments with butyric acid. Our findings demonstrate that inulin, by influencing the intestinal flora, modifies the activity of EGCs to effectively reduce colonic inflammation in T2DM mice.}, }
@article {pmid37840733, year = {2023}, author = {Hua, F and Cui, E and Lv, L and Wang, B and Li, L and Lu, H and Chen, N and Chen, W}, title = {Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1243102}, pmid = {37840733}, issn = {1664-302X}, abstract = {INTRODUCTION: Acute lung injury (ALI) is a severe respiratory tract disorder facilitated by dysregulated inflammation, oxidative stress and intestinal ecosystem. Fecal microbiota transplantation (FMT) is a rapid method for gut microbiota (GM) reconstruction. Furthermore, our previous studies have confirmed that human umbilical cord mesenchymal stromal cells (HUC-MSCs) can alleviate ALI by improving GM composition. Therefore, we aimed to explore the efficacy and mechanism of FMT from HUC-MSCs-treated mice on ALI.<br><br>METHODS: In brief, fresh feces from HUC-MSCs-treated mice were collected for FMT, and the mice were randomly assigned into NC, FMT, LPS, ABX-LPS, and ABX-LPS-FMT groups (n = 12/group). Subsequently, the mice were administrated with antibiotic mixtures to deplete GM, and given lipopolysaccharide and FMT to induce ALI and rebuild GM. Next, the therapeutic effect was evaluated by bronchoalveolar lavage fluid (BALF) and histopathology. Immune cells in peripheral blood and apoptosis in lung tissues were measured. Furthermore, oxidative stress- and inflammation-related parameter levels were tested in BALF, serum, lung and ileal tissues. The expressions of apoptosis-associated, TLR4/NF-&#x3ba;B pathway-associated, Nrf2/HO-1 pathway related and tightly linked proteins in the lung and ileal tissues were assessed. Moreover, 16S rRNA was conducted to assess GM composition and distribution.<br><br>RESULTS: Our results revealed that FMT obviously improved the pathological damage of lung and ileum, recovered the immune system of peripheral blood, decreased the cell apoptosis of lung, and inhibited inflammation and oxidative stress in BALF, serum, lung and ileum tissues. Moreover, FMT also elevated ZO-1, claudin-1, and occludin protein expressions, activating the Nrf2/HO-1 pathway but hindering the TLR4/NF-&#x3ba;B pathway. Of note, the relative abundances of Bacteroides, Christensenella, Coprococcus, and Roseburia were decreased, while the relative abundances of Xenorhabdus, Sutterella, and Acinetobacter were increased in the ABX-LPS-FMT group.<br><br>CONCLUSION: FMT from HUC-MSCs-treated mice may alleviate ALI by inhibiting inflammation and reconstructing GM, additionally, we also found that the TLR4/NF-&#x3ba;B and Nrf2/HO-1 pathways may involve in the improvement of FMT on ALI, which offers novel insights for the functions and mechanisms of FMT from HUC-MSCs-treated mice on ALI.}, }
@article {pmid37840104, year = {2023}, author = {Jayachandran, M and Qu, S}, title = {Non-alcoholic fatty liver disease and gut microbial dysbiosis- underlying mechanisms and gut microbiota mediated treatment strategies.}, journal = {Reviews in endocrine &amp; metabolic disorders}, volume = {24}, number = {6}, pages = {1189-1204}, pmid = {37840104}, issn = {1573-2606}, support = {2018YFC1314101//The National Key R&amp;D Program of China/ ; 2016YFC1305600//The National Key R&amp;D Program of China/ ; 81970677//National Natural Science Foundation of China/ ; 82170861//National Natural Science Foundation of China/ ; 22120190210//Fundamental Research Funds for the Central Universities of Tongji University/ ; SHDC2020CR1017B//Clinical Research Plan of SHDC/ ; 19DZ1910200//Shanghai Committee of Science and Technology, China/ ; 17DZ1910603//Shanghai Committee of Science and Technology, China/ ; 18411951803//Shanghai Committee of Science and Technology, China/ ; }, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/therapy/metabolism ; *Gastrointestinal Microbiome ; Dysbiosis/therapy/microbiology ; Liver/metabolism ; Prebiotics ; Obesity/metabolism ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is by far the most prevalent form of liver disease worldwide. It's also the leading cause of liver-related hospitalizations and deaths. Furthermore, there is a link between obesity and NAFLD risk. A projected 25% of the world's population grieves from NAFLD, making it the most common chronic liver disorder. Several factors, such as obesity, oxidative stress, and insulin resistance, typically accompany NAFLD. Weight loss, lipid-lowering agents, thiazolidinediones, and metformin help prominently control NAFLD. Interestingly, pre-clinical studies demonstrate gut microbiota's potential causal role in NAFLD. Increased intestinal permeability and unhindered transport of microbial metabolites into the liver are the major disruptions due to gut microbiome dysbiosis, contributing to the development of NAFLD by dysregulating the gut-liver axis. Hence, altering the pathogenic bacterial population using probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) could benefit patients with NAFLD. Therefore, it is crucial to acknowledge the importance of microbiota-mediated therapeutic approaches for NAFLD and comprehend the underlying mechanisms that establish a connection between NAFLD and gut microbiota. This review provides a comprehensive overview of the affiliation between dysbiosis of gut microbiota and the progress of NAFLD, as well as the potential benefits of prebiotic, probiotic, synbiotic supplementation, and FMT in obese individuals with NAFLD.}, }
@article {pmid37839834, year = {2023}, author = {Yang, Y and Lv, L and Shi, S and Cai, G and Yu, L and Xu, S and Zhu, T and Su, X and Mao, N and Zhang, Y and Peng, S and He, J and Liu, Z and Wang, D}, title = {Polysaccharide from walnut green husk alleviates liver inflammation and gluconeogenesis dysfunction by altering gut microbiota in ochratoxin A-induced mice.}, journal = {Carbohydrate polymers}, volume = {322}, number = {}, pages = {121362}, doi = {10.1016/j.carbpol.2023.121362}, pmid = {37839834}, issn = {1879-1344}, mesh = {Mice ; Rats ; Animals ; Gluconeogenesis ; *Juglans ; *Gastrointestinal Microbiome ; Liver ; Polysaccharides/pharmacology/therapeutic use ; Inflammation/chemically induced/drug therapy/metabolism ; }, abstract = {Walnut green husk polysaccharides (WGP) are isolated from the walnut green husk with a mean molecular weight of 12.77 kDa. The structural characterization revealed by methylation and NMR analysis indicated that WGP might consist of →4-α-D-Galp-(1→, α-D-Galp (1→, and →2)-α-L-Rhap-(1→. Previous studies have been demonstrated that WGP effectively prevented liver injury and modulated gut microbiota in high fructose-treated mice and high fat diet-treated rats. In this study, we found for the first time that WGP presenting outstanding protective effects on liver inflammation and gluconeogenesis dysfunction induced by ochratoxin A (OTA) in mice. Firstly, WGP decreased oxidative stress, down-regulated the expression of inflammatory factors and inhibited the TLR4/p65/IκBα pathway in the liver. Then, WGP reversed OTA-induced lower phosphoenolpyruvate carboxyl kinase (PEPCK), and glucose 6-phosphatase (G6PC) activities in the liver. Furthermore, WGP increased the diversity of gut microbiota and the abundance of beneficial bacteria, especially Lactobacillus and Akkermansia. Importantly, the results of fecal microbiota transplantation (FMT) experiment further confirmed that gut microbiota involved in the protective effects of WGP on liver damage induced by OTA. Our results indicated that the protective effect of WGP on liver inflammation and gluconeogenesis dysfunction caused by OTA may be due to the regulation of gut microbiota.}, }
@article {pmid37839771, year = {2024}, author = {Wang, C and Jiang, S and Zheng, H and An, Y and Zheng, W and Zhang, J and Liu, J and Lin, H and Wang, G and Wang, F}, title = {Integration of gut microbiome and serum metabolome revealed the effect of Qing-Wei-Zhi-Tong Micro-pills on gastric ulcer in rats.}, journal = {Journal of ethnopharmacology}, volume = {319}, number = {Pt 3}, pages = {117294}, doi = {10.1016/j.jep.2023.117294}, pmid = {37839771}, issn = {1872-7573}, mesh = {Male ; Rats ; Animals ; *Stomach Ulcer/chemically induced/drug therapy ; *Gastrointestinal Microbiome ; Rats, Wistar ; Metabolome ; Acetic Acid ; }, abstract = {Qing-Wei-Zhi-Tong Micro-pills (QWZT) is herbal compound used in the treatment of GU, whose functions include clearing the stomach and fire, softening the liver and relieving pain. However, its mechanistic profile on host intestinal microbiota and metabolism has not been determined.<br><br>AIM OF THE STUDY: The present study aimed to observe the healing effect of QWZT on acetic acid-induced gastric ulcer in a rat model and to preliminarily elucidate its possible therapeutic mechanism from the perspective of host intestinal microbiota and metabolism.<br><br>MATERIALS AND METHODS: The Wistar male rats (7 weeks old; weight 180-200&#xa0;g) were randomly divided into normal control group (NC), acetic acid-induced gastric ulcer group (GU), and QWZT treatment group (High dose: 1250&#xa0;mg/kg/day, Middle dose: 625&#xa0;mg/kg/day, Low dose: 312.5&#xa0;mg/kg/day) of 6 rats each. An acetic acid-induced gastric ulcer rat model was constructed based on anatomical surgery. QWZT (High dose, Middle dose, and Low dose) was used to treat gastric ulcer rats for 7 days by gavage. At the end of treatment, the body weight, macroscopic condition of gastric tissue ulcers, pathological changes (HE staining), inflammatory factors, oxidative stress factors, and endocrine factors were assessed in each group of rats. Fresh feces and serum from each group of rats were collected for microbiome and metabolome analysis on the machine, respectively. Drug-disease common targets and functional pathways were captured based on network pharmacology. The complex network of Herbs-Targets-Pathways-Metabolites-Microbiota interactions was constructed. Ultimately, Fecal Microbiota Transplantation (FMT) evaluated the contribution of gut microbiota in disease.<br><br>RESULTS: QWZT increased the abundance of beneficial bacteria (Bacteroides, Alloprevotella, Rikenellaceae_RC9_gut_group, Lactobacillus, Lachnospiraceae_NK4A136_group, Parabacteroides, etc.), reduced the abundance of harmful bacteria (Micromonospora, Geobacter, Nocardioides, and Arenimonas, etc.), reduced the levels of inflammatory mediators (12,13-EpOME, 9,10-Epoxyoctadecenoic acid, SM(d18:1/16:0) and Leukotriene A4, etc.), restored host metabolic disorders (Linoleic acid metabolism, Glycerophospholipid metabolism, and Arachidonic acid metabolism), and regulated the level of cytokines (IL-6, TNF-a, SOD, MDA, PEG-2 and NO), ultimately exerting an anti-ulcer effect. Apart from that, FMT improved acetic acid-induced gastric ulcers in rats.<br><br>CONCLUSION: QWZT improved acetic acid-induced gastric ulcers in rats by remodeling intestinal microbiota and regulating host metabolism. This work may promote the process of developing and utilizing clinical applications of QWZT.}, }
@article {pmid37839469, year = {2024}, author = {Tao, Y and Zhou, H and Li, Z and Wu, H and Wu, F and Miao, Z and Shi, H and Huang, F and Wu, X}, title = {TGR5 deficiency-induced anxiety and depression-like behaviors: The role of gut microbiota dysbiosis.}, journal = {Journal of affective disorders}, volume = {344}, number = {}, pages = {219-232}, doi = {10.1016/j.jad.2023.10.072}, pmid = {37839469}, issn = {1573-2517}, mesh = {Animals ; Mice ; *Anxiety/genetics/microbiology ; *Depression/genetics/microbiology ; *Dysbiosis/complications ; *Gastrointestinal Microbiome ; Mice, Knockout ; Serotonin ; *Receptors, G-Protein-Coupled/genetics ; }, abstract = {BACKGROUND AND PURPOSE: Anxiety and depression have been associated with imbalances in the gut microbiota and bile acid metabolism. Takeda G protein-coupled receptor 5 (TGR5), a bile acid receptor involved in metabolism, is influenced by the gut microbiota. This study aimed to investigate the relationship between anxiety, depression, and microbiota using TGR5 knockout mice.<br><br>METHODS: We employed the following methods: (1) Assessment of behavioral changes, (2) Measurement of 5-HT levels and protein expression, (3) Analysis of stool samples, (4) Utilization of gene sequencing and statistical analysis to identify microbial signatures, (5) Examination of correlations between microbial signatures and 5-HT levels, and (6) Fecal microbiota transplantation experiments of TGR5[-/-] mice.<br><br>RESULTS: The deletion of TGR5 was found to result in increased anxiety- and depression-like behaviors in mice. TGR5 knockout mice exhibited significant reductions in 5-hydroxytryptamine (5-HT) levels in both serum and hippocampus, accompanied by a decrease in the expression of 5-HT1A receptor in the hippocampus. Moreover, TGR5 deficiency was associated with a decrease in the species richness of the gut microbiota. Specifically, the gut microbiota compositions of TGR5 knockout mice displayed distinct differences compared to their littermates, characterized by higher abundances of Anaeroplasma, Prevotella, Staphylococcus, Jeotgalicoccus, and Helicobacter, and a lower abundance of Bifidobacterium. Notably, a strong association between Jeotgalicoccus as well as Staphylococcus and serum 5-HT levels was observed in co-occurrence network. Furthermore, mice that received fecal microbiota transplants from TGR5[-/-] mice displayed anxiety and depression -like behaviors, accompanied by alterations in 5-HT levels in the hippocampus and serum.<br><br>LIMITATIONS: Study limitations for gut bacteria were analyzed at the genus level only.<br><br>CONCLUSION: TGR5 deletion in mice induces anxiety and depression-like behaviors, linked to reduced 5-HT levels in serum and the hippocampus. Gut microbiota changes play a direct role in these behaviors and serotonin alterations. This implicates TGR5 and gut bacteria in mood regulation, with potential therapeutic implications.}, }
@article {pmid37834066, year = {2023}, author = {Zhou, Y and Bi, Z and Hamilton, MJ and Zhang, L and Su, R and Sadowsky, MJ and Roy, S and Khoruts, A and Chen, C}, title = {p-Cresol Sulfate Is a Sensitive Urinary Marker of Fecal Microbiota Transplantation and Antibiotics Treatments in Human Patients and Mouse Models.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834066}, issn = {1422-0067}, support = {R21 AI091907/AI/NIAID NIH HHS/United States ; R01 DA043252/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; Fecal Microbiota Transplantation/methods ; Vancomycin ; *Clostridioides difficile ; Treatment Outcome ; Feces/chemistry ; *Clostridium Infections/therapy ; Anti-Bacterial Agents/pharmacology/therapeutic use/analysis ; Disease Models, Animal ; Recurrence ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) and also a potential therapy for other diseases associated with dysbiotic gut microbiota. Monitoring metabolic changes in biofluids and excreta is a noninvasive approach to identify the biomarkers of microbial recolonization and to understand the metabolic influences of FMT on the host. In this study, the pre-FMT and post FMT urine samples from 11 rCDI patients were compared through metabolomic analyses for FMT-induced metabolic changes. The results showed that p-cresol sulfate in urine, a microbial metabolite of tyrosine, was rapidly elevated by FMT and much more responsive than other microbial metabolites of aromatic amino acids (AAAs). Because patients were treated with vancomycin prior to FMT, the influence of vancomycin on the microbial metabolism of AAAs was examined in a mouse feeding trial, in which the decreases in p-cresol sulfate, phenylacetylglycine, and indoxyl sulfate in urine were accompanied with significant increases in their AAA precursors in feces. The inhibitory effects of antibiotics and the recovering effects of FMT on the microbial metabolism of AAAs were further validated in a mouse model of FMT. Overall, urinary p-cresol sulfate may function as a sensitive and convenient therapeutic indicator on the effectiveness of antibiotics and FMT for the desired manipulation of gut microbiota in human patients.}, }
@article {pmid37834010, year = {2023}, author = {Jamshidi, P and Farsi, Y and Nariman, Z and Hatamnejad, MR and Mohammadzadeh, B and Akbarialiabad, H and Nasiri, MJ and Sechi, LA}, title = {Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834010}, issn = {1422-0067}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Irritable Bowel Syndrome/therapy/etiology ; *Gastrointestinal Microbiome ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Feces ; }, abstract = {Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT in relieving symptoms in IBS patients. A thorough search was executed on PubMed/Medline and Embase databases until 14 June 2023, including all studies on FMT use in IBS patients. We examined the efficiency of FMT in reducing patients' symptoms overall and in particular subgroups, classified by placebo preparation, FMT preparation, frequency, and route of administration. Among 1015 identified studies, seven met the inclusion criteria for the meta-analysis. The overall symptomatology of FMT-treated IBS patients did not significantly differ from the control group (Odds Ratio (OR) = 0.99, 95% Confidence Interval (CI) 0.39-2.5). Multiple doses of FMT compared with non-FMT placebo, or single-donor FMT therapy compared with autologous FMT placebo also showed no significant benefit (OR = 0.32, 95%CI (0.07-1.32), p = 0.11, and OR = 1.67, 95%CI (0.59-4.67), p = 0.32, respectively). However, a single dose of multiple-donor FMT administered via colonoscopy (lower gastrointestinal (GI) administration) significantly improved patient symptoms compared with autologous FMT placebo (OR = 2.54, 95%CI (1.20-5.37), p = 0.01, and OR = 2.2, 95%CI (1.20-4.03), p = 0.01, respectively). The studies included in the analysis showed a low risk of bias and no publication bias. In conclusion, lower GI administration of a single dose of multiple-donor FMT significantly alleviates patient complaints compared with the autologous FMT used as a placebo. The underlying mechanisms need to be better understood, and further experimental studies are desired to fill the current gaps.}, }
@article {pmid37833682, year = {2023}, author = {Diwan, B and Yadav, R and Singh, A and Kumar, D and Sharma, R}, title = {Murine sterile fecal filtrate is a potent pharmacological agent that exerts age-independent immunomodulatory effects in RAW264.7 macrophages.}, journal = {BMC complementary medicine and therapies}, volume = {23}, number = {1}, pages = {362}, pmid = {37833682}, issn = {2662-7671}, support = {IFA17-LSPA79//Department of Science and Technology, Ministry of Science and Technology, India/ ; }, mesh = {Animals ; Mice ; *Antioxidants/chemistry ; *Interleukin-10 ; Signal Transduction ; Reactive Oxygen Species/metabolism ; Lipopolysaccharides/pharmacology ; Macrophages ; Anti-Inflammatory Agents/pharmacology ; Cytokines/metabolism ; Nitric Oxide/metabolism ; }, abstract = {BACKGROUND: Sterile fecal filtrate (SFF) is being considered a safer alternative to fecal microbiota transplantation (FMT) therapy; however, its bioactive potency is very little understood. The present study thus assessed the age-dependent immunostimulatory and immunomodulatory attributes of murine SFF in vitro.<br><br>METHODS: SFF from young (Y-SFF) and old (O-SFF) Swiss albino mice were prepared. Immunostimulatory and immunomodulatory effects of SFF were evaluated in resting and lipopolysaccharide (LPS) stimulated macrophage cells by measuring intracellular reactive oxygen species (ROS), nitric oxide (NO) production, inflammatory cytokines profile, as well as gene expression of oxidative and inflammatory transcription factors. SFF were also evaluated for native antioxidant capacity by measuring DPPH and ABTS free radical scavenging activity. Bioactive components present in SFF were also determined by GC/MS analysis.<br><br>RESULTS: Both Y-SFF and O-SFF induced potent immunostimulatory effects characterized by changes in cell morphology, a significant increase in NO production, ROS levels, and an increased ratio of pro-inflammatory (IL-6, TNF-&#x3b1;, IL-1&#x3b2;) to anti-inflammatory (IL-10) secretory proteins although no significant aggravation in the transcription of NF-&#x3ba;B and Nrf-2 could be observed. Application of LPS to cells significantly augmented a pro-oxidative and pro-inflammatory response which was much higher in comparison to Y-SFF or O-SFF application alone and mediated by strong suppression of Nrf-2 gene expression. Pre-treatment of macrophages with both Y-SFF and O-SFF robustly attenuated cellular hyperresponsiveness to LPS characterized by significantly decreased levels of NO, ROS, and inflammatory cytokines while a concomitant increase in anti-inflammatory protein (IL-10) was observed. Further, both Y-SFF and O-SFF strongly resisted LPS-induced downregulation of Nrf-2 expression although O-SFF appeared to protect cells slightly better from the overall LPS threat. Neat SFF samples exhibited moderate antioxidant capacity and GC/MS analysis of SFF revealed diverse volatile organic compounds characterized by alkanes, organosulphur compounds, furans, amides, amino acids, and antimicrobial elements.<br><br>CONCLUSION: Our results indicate that SFF is a potent stimulant of macrophages and confers strong anti-inflammatory effects regardless of donor age thereby suggesting its therapeutic efficacy in lieu of FMT therapy.}, }
@article {pmid37831533, year = {2023}, author = {Keller, JJ and Terveer, EM}, title = {Editorial: Continuous monitoring to improve outcome of treatment-the next step towards safe and effective faecal microbiota transplantation.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {58}, number = {9}, pages = {946-947}, doi = {10.1111/apt.17694}, pmid = {37831533}, issn = {1365-2036}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; Feces ; *Colitis, Ulcerative ; Treatment Outcome ; }, }
@article {pmid37831529, year = {2023}, author = {Lesmana, E and Grover, M}, title = {Editorial: Faecal microbiota transplantation in IBS-Moving closer or away from success?.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {58}, number = {9}, pages = {950-951}, doi = {10.1111/apt.17724}, pmid = {37831529}, issn = {1365-2036}, support = {R01 AI027998/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Fecal Microbiota Transplantation ; *Irritable Bowel Syndrome/therapy ; Feces ; *Microbiota ; }, }
@article {pmid37831526, year = {2023}, author = {Su, Q and Yau, YK and Ng, SC}, title = {Editorial: Faecal microbiota transplantation in IBS-Moving closer or away from success? Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {58}, number = {9}, pages = {952-953}, doi = {10.1111/apt.17729}, pmid = {37831526}, issn = {1365-2036}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Irritable Bowel Syndrome/therapy ; Feces ; *Microbiota ; }, }
@article {pmid37831525, year = {2023}, author = {Baunwall, SMD and Hansen, MM and Andreasen, SE and Eriksen, MK and Rågård, N and Kelsen, J and Grosen, AK and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Editorial: Continuous monitoring to improve outcome of treatment-the next step towards safe and effective faecal microbiota transplantation. Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {58}, number = {9}, pages = {948-949}, doi = {10.1111/apt.17721}, pmid = {37831525}, issn = {1365-2036}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; Feces ; *Clostridium Infections ; Treatment Outcome ; }, }
@article {pmid37830929, year = {2023}, author = {Qian, X and Jiang, H and Wu, Y and Shao, H and He, W and He, Y and Bao, X and He, L and Jia, Y and Xu, Z}, title = {Fecal microbiota transplantation combined with prebiotics ameliorates ulcerative colitis in mice.}, journal = {Future microbiology}, volume = {18}, number = {}, pages = {1251-1263}, doi = {10.2217/fmb-2023-0001}, pmid = {37830929}, issn = {1746-0921}, mesh = {Mice ; Animals ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy ; Feces/microbiology ; Prebiotics ; Oligosaccharides ; }, abstract = {Aim: To investigate the effect of treatment with fecal microbiota transplantation (FMT) and galacto- and fructo-oligosaccharides on ulcerative colitis (UC) in mice. Materials &amp; methods: A total of 90 mice, divided into nine groups, were administered FMT or prebiotics or combined treatment. The disease activity index scores, gut microbiota and inflammation factors were evaluated. Results: The treatment using FMT combined with galacto- and fructo-oligosaccharides in a 9:1 ratio significantly reduced intestinal barrier damage and alleviated symptoms of UC. Lactobacillus and Bifidobacterium and short-chain fatty acids were significantly increased after the combined treatment. Conclusion: The results demonstrate that FMT with prebiotics is a new method for UC treatment.}, }
@article {pmid37828613, year = {2023}, author = {Guo, C and Kong, L and Xiao, L and Liu, K and Cui, H and Xin, Q and Gu, X and Jiang, C and Wu, J}, title = {The impact of the gut microbiome on tumor immunotherapy: from mechanism to application strategies.}, journal = {Cell &amp; bioscience}, volume = {13}, number = {1}, pages = {188}, pmid = {37828613}, issn = {2045-3701}, support = {82272819//National Natural Science Foundation of China/ ; 81972888//National Natural Science Foundation of China/ ; JNL202204A//the Research Project of Jinan Microecological Biomedicine Shandong Laboratory/ ; JNL202219B//the Research Project of Jinan Microecological Biomedicine Shandong Laboratory/ ; JNL-2023017D//the Research Project of Jinan Microecological Biomedicine Shandong Laboratory/ ; BE2022840//the Primary Research &amp; Development Plan of Jiangsu Province/ ; SYS202202//Shandong Provincial Laboratory Project/ ; 2020YLXK007//the Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine/ ; }, abstract = {Immunotherapy is one of the fastest developing areas in the field of oncology. Many immunological treatment strategies for refractory tumors have been approved and marketed. Nevertheless, much clinical and preclinical experimental evidence has shown that the efficacy of immunotherapy in tumor treatment varies markedly among individuals. The commensal microbiome mainly colonizes the intestinal lumen in humans, is affected by a variety of factors and exhibits individual variation. Moreover, the gut is considered the largest immune organ of the body due to its influence on the immune system. In the last few decades, with the development of next-generation sequencing (NGS) techniques and in-depth research, the view that the gut microbiota intervenes in antitumor immunotherapy through the immune system has been gradually confirmed. Here, we review important studies published in recent years focusing on the influences of microbiota on immune system and the progression of malignancy. Furthermore, we discuss the mechanism by which microbiota affect tumor immunotherapy, including immune checkpoint blockade (ICB) and adoptive T-cell therapy (ACT), and strategies for modulating the microbial composition to facilitate the antitumor immune response. Finally, opportunity and some challenges are mentioned to enable a more systematic understanding of tumor treatment in the future and promote basic research and clinical application in related fields.}, }
@article {pmid37824034, year = {2023}, author = {Zhou, J and Qiu, X and Chen, X and Ma, S and Chen, Z and Wang, R and Tian, Y and Jiang, Y and Fan, L and Wang, J}, title = {Comprehensive Analysis of Gut Microbiota Alteration in the Patients and Animal Models with Polycystic Ovary Syndrome.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {61}, number = {9}, pages = {821-836}, pmid = {37824034}, issn = {1976-3794}, support = {WJ2023M169//Scientific research Project of Hubei Provincial Health Commission/ ; No. 22Y26//Scientific and Technological Project of Shiyan City of Hubei Province/ ; S202110929010//National Undergraduate Training Program for Innovation and Entrepreneurship/ ; 2016QDJZR17//Cultivating Project for Young Scholar at Hubei University of Medicine/ ; }, mesh = {Humans ; Female ; Rats ; Animals ; *Polycystic Ovary Syndrome/drug therapy/etiology ; *Gastrointestinal Microbiome ; Letrozole/pharmacology/therapeutic use ; Disease Models, Animal ; }, abstract = {Polycystic ovary syndrome (PCOS) is a common disease of endocrine-metabolic disorder, and its etiology remains largely unknown. The gut microbiota is possibly involved in PCOS, while the association remains unclear. The comprehensive analysis combining gut microbiota with PCOS typical symptoms was performed to analyze the role of gut microbiota in PCOS in this study. The clinical patients and letrozole-induced animal models were determined on PCOS indexes and gut microbiota, and fecal microbiota transplantation (FMT) was conducted. Results indicated that the animal models displayed typical PCOS symptoms, including disordered estrous cycles, elevated testosterone levels, and ovarian morphological change; meanwhile, the symptoms were improved after FMT. Furthermore, the microbial diversity exhibited disordered, and the abundance of the genus Ruminococcus and Lactobacillus showed a consistent trend in PCOS rats and patients. The microbiota diversity and several key genera were restored subjected to FMT, and correlation analysis also supported relevant conclusions. Moreover, LEfSe analysis showed that Gemmiger, Flexispira, and Eubacterium were overrepresented in PCOS groups. Overall, the results indicate the involvement of gut microbiota in PCOS and its possible alleviation of endocrinal and reproductive dysfunctions through several special bacteria taxa, which can function as the biomarker or potential target for diagnosis and treatment. These results can provide the new insights for treatment and prevention strategies of PCOS.}, }
@article {pmid37823985, year = {2023}, author = {Jothimani, D and Paramasivam, R and Manoharan, M and Ramachandran, H and Muthusamy, S and Simon, E and Ravichandran, J and Rela, M}, title = {Fecal calprotectin in patients with liver cirrhosis.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {42}, number = {6}, pages = {818-823}, pmid = {37823985}, issn = {0975-0711}, mesh = {Humans ; Leukocyte L1 Antigen Complex/metabolism ; Prospective Studies ; Biomarkers ; Liver Cirrhosis/complications ; *Sepsis/complications ; Feces ; *Acute-On-Chronic Liver Failure/diagnosis/etiology ; }, abstract = {BACKGROUND AND OBJECTIVES: Sepsis is the most challenging complication in patients with liver cirrhosis. It destabilizes patients leading to worsening of liver dysfunction and increased mortality. Intestinal bacterial dysbiosis, release of endotoxins, increased gut permeability and associated immune dysregulation have been described in cirrhotic patients with septic complications. Calprotectin is a major cytosolic protein secreted by the inflammatory cells and has been widely studied in patients with inflammatory bowel disease. We aimed at evaluating the role of fecal calprotectin (FCAL) in patients with liver cirrhosis.<br><br>METHODS: A prospective, observational study on the utility of FCAL test was conducted in patients with liver cirrhosis. Fifteen milligrams of fecal specimen was collected and analyzed within 48&#xa0;hours of hospitalization from patients with end-stage liver disease (ESLD), acute-on-chronic liver failure (ACLF) and at the time of outpatient visit for stable cirrhotics. Five healthy volunteers underwent FCAL test as control population.<br><br>RESULTS: The mean FCAL (&#xb5;g/g) level in healthy control (n&#x2009;=&#x2009;5), stable cirrhotics (n&#x2009;=&#x2009;10), ESLD (n&#x2009;=&#x2009;10) and ACLF (n&#x2009;=&#x2009;10) patients was 109.2 (95% CI:&#x2009;-&#x2009;53.39 to 271.79), 143.3 (95% CI: 50.5-236.45), 176.9 (95% CI: 122.93-230.87) and 543.5 (95% CI: 207.09-879.91) (p&#x2009;=&#x2009;0.005), respectively. Sepsis was identified in 13 (43.3%) patients. Area under the receiver-operating characteristics curve (AUROC) of FCAL was 0.80 (p&#x2009;=&#x2009;0.005) and FCAL&#x2009;&#x2265;&#x2009;200&#xa0;&#xb5;g/g (OR&#x2009;=&#x2009;10.8, p&#x2009;=&#x2009;0.006) was associated with sepsis. Nine (25.7%) patients expired. FCAL level was significantly higher in dead patients compared to survivors (mean, 493.67 (95% CI: 142.20-845.14) vs. 199.71 (95% CI: 99.84-299.59) &#x3bc;g/g,p&#x2009;=&#x2009;0.005.<br><br>CONCLUSIONS: FCAL levels are increased in patients with chronic liver disease, with highest level in ACLF. An FCAL level of&#x2009;&#x2265;&#x2009;200&#xa0;&#xb5;g/g was associated with sepsis and mortality in cirrhotic patients. Larger studies are required to identify the role of FCAL in these patients. Early identification and initiation of anti-microbials may mitigate sepsis and reduce mortality.}, }
@article {pmid37823484, year = {2024}, author = {Straub, TJ and Lombardo, MJ and Bryant, JA and Diao, L and Lodise, TP and Freedberg, DE and Wortman, JR and Litcofsky, KD and Hasson, BR and McGovern, BH and Ford, CB and Henn, MR}, title = {Impact of a Purified Microbiome Therapeutic on Abundance of Antimicrobial Resistance Genes in Patients With Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {78}, number = {4}, pages = {833-841}, pmid = {37823484}, issn = {1537-6591}, support = {//Seres Therapeutics/ ; }, mesh = {Adult ; Humans ; Female ; Aged ; Male ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; *Clostridioides difficile/genetics ; Drug Resistance, Bacterial ; *Microbiota ; *Clostridium Infections/microbiology ; Bacteria ; Firmicutes ; }, abstract = {BACKGROUND: The gastrointestinal microbiota is an important line of defense against colonization with antimicrobial resistant (AR) bacteria. In this post hoc analysis of the phase 3 ECOSPOR III trial, we assessed impact of a microbiota-based oral therapeutic (fecal microbiota spores, live; VOWST Oral Spores [VOS], formerly SER-109]; Seres Therapeutics) compared with placebo, on AR gene (ARG) abundance in patients with recurrent Clostridioides difficile infection (rCDI).<br><br>METHODS: Adults with rCDI were randomized to receive VOS or placebo orally for 3 days following standard-of-care antibiotics. ARG and taxonomic profiles were generated using whole metagenomic sequencing of stool at baseline and weeks 1, 2, 8, and 24 posttreatment.<br><br>RESULTS: Baseline (n = 151) and serial posttreatment stool samples collected through 24 weeks (total N = 472) from 182 patients (59.9% female; mean age: 65.5 years) in ECOSPOR III as well as 68 stool samples obtained at a single time point from a healthy cohort were analyzed. Baseline ARG abundance was similar between arms and significantly elevated versus the healthy cohort. By week 1, there was a greater decline in ARG abundance in VOS versus placebo (P = .003) in association with marked decline of Proteobacteria and repletion of spore-forming Firmicutes, as compared with baseline. We observed abundance of Proteobacteria and non-spore-forming Firmicutes were associated with ARG abundance, while spore-forming Firmicutes abundance was negatively associated.<br><br>CONCLUSIONS: This proof-of-concept analysis suggests that microbiome remodeling with Firmicutes spores may be a potential novel approach to reduce ARG colonization in the gastrointestinal tract.}, }
@article {pmid37823111, year = {2023}, author = {He, G and Chen, T and Huang, L and Zhang, Y and Feng, Y and Liu, Q and Yin, X and Qu, S and Yang, C and Wan, J and Liang, L and Yan, J and Liu, W}, title = {Tibetan tea reduces obesity brought on by a high-fat diet and modulates gut flora in mice.}, journal = {Food science &amp; nutrition}, volume = {11}, number = {10}, pages = {6582-6595}, pmid = {37823111}, issn = {2048-7177}, abstract = {It has been shown that Tibetan tea (TT) inhibits obesity and controls lipid metabolism. The fundamental processes by which TT prevents obesity are yet entirely unknown. Consequently, this research aimed to ascertain if TT may prevent obesity by modifying the gut flora. Our research demonstrated that TT prevented mice from gaining weight and accumulating fat due to the high-fat diet (HFD), decreased levels of blood total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and raised levels of high-density lipoprotein cholesterol (HDL-C). Adipogenesis-related genes such as acetyl-Coenzyme A carboxylase 1 (ACC1, LOC107476), fatty acid synthase (Fas, LOC14104), sterol regulatory element-binding protein-1c (SREBP-1c, LOC20787), CCAAT/enhancer-binding protein α (C/EBPα, LOC12606), stearoyl-CoA desaturase 1 (SCD1, LOC20249), and peroxisome proliferator-activated receptor γ (PPARγ, LOC19016) had their expression downregulated by lowering the Firmicutes/Bacteroidetes (F/B) ratio and controlling the number of certain gut bacteria. TT also alleviated HFD-induced abnormalities of the gut microbiota. The Muribaculaceae, Lachnospiraceae NK4A136_group, Alistipes, and Odoribacter families were identified as the major beneficial gut microorganisms using Spearman's correlation analysis. Fecal microbiota transplantation (FMT) demonstrated that TT's anti-obesity and gut microbiota-modulating benefits might be transmitted to mice on an HFD, demonstrating that one of TT's targets for preventing obesity is the gut microbiota. TT also increased the amount of short-chain fatty acids (SCFAs) in the feces, including acetic, propionic, and butyric acids. These results indicate the possible development of TT as a prebiotic to combat obesity and associated disorders. These results suggest that TT may act as a prebiotic against obesity and its associated diseases.}, }
@article {pmid37822750, year = {2023}, author = {Zhu, J and Lyu, J and Zhao, R and Liu, G and Wang, S}, title = {Gut macrobiotic and its metabolic pathways modulate cardiovascular disease.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1272479}, pmid = {37822750}, issn = {1664-302X}, abstract = {Thousands of microorganisms reside in the human gut, and extensive research has demonstrated the crucial role of the gut microbiota in overall health and maintaining homeostasis. The disruption of microbial populations, known as dysbiosis, can impair the host's metabolism and contribute to the development of various diseases, including cardiovascular disease (CVD). Furthermore, a growing body of evidence indicates that metabolites produced by the gut microbiota play a significant role in the pathogenesis of cardiovascular disease. These bioactive metabolites, such as short-chain fatty acids (SCFAs), trimethylamine (TMA), trimethylamine N-oxide (TMAO), bile acids (BAs), and lipopolysaccharides (LPS), are implicated in conditions such as hypertension and atherosclerosis. These metabolites impact cardiovascular function through various pathways, such as altering the composition of the gut microbiota and activating specific signaling pathways. Targeting the gut microbiota and their metabolic pathways represents a promising approach for the prevention and treatment of cardiovascular diseases. Intervention strategies, such as probiotic drug delivery and fecal transplantation, can selectively modify the composition of the gut microbiota and enhance its beneficial metabolic functions, ultimately leading to improved cardiovascular outcomes. These interventions hold the potential to reshape the gut microbial community and restore its balance, thereby promoting cardiovascular health. Harnessing the potential of these microbial metabolites through targeted interventions offers a novel avenue for tackling cardiovascular health issues. This manuscript provides an in-depth review of the recent advances in gut microbiota research and its impact on cardiovascular health and offers a promising avenue for tackling cardiovascular health issues through gut microbiome-targeted therapies.}, }
@article {pmid37822139, year = {2023}, author = {Tie, Y and Huang, Y and Chen, R and Li, L and Chen, M and Zhang, S}, title = {Current insights on the roles of gut microbiota in inflammatory bowel disease-associated extra-intestinal manifestations: pathophysiology and therapeutic targets.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2265028}, pmid = {37822139}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/therapy ; *Inflammatory Bowel Diseases/complications/therapy/diagnosis ; *Microbiota ; Fecal Microbiota Transplantation ; Cytokines ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease of the gastrointestinal tract. In addition to digestive symptoms, patients with IBD may also develop extra-intestinal manifestations (EIMs), the etiology of which remains undefined. The gut microbiota has been reported to exert a critical role in the pathogenesis of IBD, with a similar pattern of gut dysbiosis observed between patients with IBD and those with EIMs. Therefore, it is hypothesized that the gut microbiota is also involved in the pathogenesis of EIMs. The potential mechanisms are presented in this review, including: 1) impaired gut barrier: dysbiosis induces pore formation in the intestinal epithelium, and activates pattern recognition receptors to promote local inflammation; 2) microbial translocation: intestinal pathogens, antigens, and toxins translocate via the impaired gut barrier into extra-intestinal sites; 3) molecular mimicry: certain microbial antigens share similar epitopes with self-antigens, inducing inflammatory responses targeting extra-intestinal tissues; 4) microbiota-related metabolites: dysbiosis results in the dysregulation of microbiota-related metabolites, which could modulate the differentiation of lymphocytes and cytokine production; 5) immunocytes and cytokines: immunocytes are over-activated and pro-inflammatory cytokines are excessively released. Additionally, we summarize microbiota-related therapies, including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation, to promote better clinical management of IBD-associated EIMs.}, }
@article {pmid37821652, year = {2023}, author = {Yost, RT and Fowler, AE and Adler, LS}, title = {Gut Transplants from Bees Fed an Antipathogenic Pollen Diet Do Not Confer Pathogen Resistance to Recipients.}, journal = {Microbial ecology}, volume = {86}, number = {4}, pages = {3133-3137}, pmid = {37821652}, issn = {1432-184X}, support = {2128221//National Science Foundation/ ; NE2001//U.S. Department of Agriculture/ ; }, mesh = {Bees ; Animals ; Pollen ; Diet/veterinary ; *Microbiota ; *Gastrointestinal Microbiome ; Crithidia ; *Biological Products ; }, abstract = {Pollinators are threatened by diverse stressors, including microbial pathogens such as Crithidia bombi. Consuming sunflower pollen dramatically reduces C. bombi infection in the bumble bee Bombus impatiens, but the mechanism behind this medicinal effect is unclear. We asked whether diet mediates resistance to C. bombi through changes in the gut microbiome. We hypothesized that sunflower pollen changes the gut microbiome, which in turn reduces Crithidia infection. To test this, we performed a gut transplant experiment. We fed donor bees either a sunflower pollen treatment or buckwheat pollen as a control treatment and then inoculated recipient bees with homogenized guts from either sunflower-fed or buckwheat-fed donor bees. All recipient bees were then fed a wildflower pollen diet. Two days after the transplant, we infected recipients with C. bombi, and 2 days later, we provided another donor gut transplant. To quantify infection, we performed both fecal screens and dissections of the recipient bees. We found no significant differences in C. bombi infection intensity or presence between bees that received sunflower-fed microbiomes versus buckwheat-fed microbiomes. This suggests that sunflower pollen's effects on pathogen resistance are not mediated by gut microbiota.}, }
@article {pmid37820424, year = {2023}, author = {Xu, C and Zhao, L and Zhou, W and Li, Y and Hu, H and Wang, Z}, title = {Synergistic effect of berberine hydrochloride and dehydrocostus lactone in the treatment of ulcerative colitis: Take gut microbiota as the target.}, journal = {International immunopharmacology}, volume = {124}, number = {Pt B}, pages = {111009}, doi = {10.1016/j.intimp.2023.111009}, pmid = {37820424}, issn = {1878-1705}, mesh = {Animals ; Mice ; *Colitis, Ulcerative/drug therapy ; *Berberine/therapeutic use ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases ; Colon ; Dextran Sulfate ; *Colitis ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Ulcerative colitis (UC) is a difficult-to-cure and recurrent inflammatory bowel disease, and it is difficult to maintain long-term results with a single drug. Inspired by clinical medication in traditional Chinese medicine, we used berberine hydrochloride (BBH) and dehydrocostus lactone (DEH) in combination for the first time and focused on studying their mechanism of treating UC based on gut microbiota. Therefore, we evaluated the therapeutic effects of BBH and DEH on DSS-induced UC mice using ELISA, HE and AB-PAS staining, 16s rDNA amplicon sequencing technology, and fecal transplantation experiments (FMT). In this study, the combination of BBH and DEH significantly relieved symptoms, colonic inflammation, and intestinal barrier damage of DSS-induced UC mice, and they did not show antagonism. In addition, the co-administration of BBH and DEH altered the composition and function of gut microbiota, with BBH increasing the abundance of key beneficial bacterial genus Akkermansia and DEH aiming to enhance species diversity and supplying intestinal proteins to prevent overconsumption. Furthermore, our data showed that BBH and DEH improve the levels of short-chain fatty acids, which also proved the positive regulation of gut microbiota by BBH and DEH. Finally, the FMT confirmed the strong correlation between BBH, DEH, and the gut microbiota. In conclusion, the co-administration of BBH and DEH protected the intestinal barrier and reduced inflammatory damage by regulating gut microbiota, targeting the key beneficial bacterial genus Akkermansia, and maintaining a normal supply of intestinal proteins.}, }
@article {pmid37820064, year = {2024}, author = {Liu, Y and Tu, J and Shi, L and Fang, Z and Fan, M and Zhang, J and Ding, L and Chen, Y and Wang, Y and Zhang, E and Xu, S and Sharma, N and Gillece, JD and Reining, LJ and Jin, L and Huang, W}, title = {CYP8B1 downregulation mediates the metabolic effects of vertical sleeve gastrectomy in mice.}, journal = {Hepatology (Baltimore, Md.)}, volume = {79}, number = {5}, pages = {1005-1018}, pmid = {37820064}, issn = {1527-3350}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; R01 DK124627/DK/NIDDK NIH HHS/United States ; R01 DK138665/DK/NIDDK NIH HHS/United States ; R56 DK129332/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Bariatric Surgery ; Down-Regulation ; Gastrectomy ; Obesity/metabolism ; *Steroid 12-alpha-Hydroxylase/metabolism ; }, abstract = {BACKGROUND AND AIMS: Although the benefits of vertical sleeve gastrectomy (VSG) surgery are well known, the molecular mechanisms by which VSG alleviates obesity and its complications remain unclear. We aim to determine the role of CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) in mediating the metabolic benefits of VSG.<br><br>APPROACH AND RESULTS: We found that expression of CYP8B1, a key enzyme in controlling the 12&#x3b1;-hydroxylated (12&#x3b1;-OH) bile acid (BA) to non-12&#x3b1;-OH BA ratio, was strongly downregulated after VSG. Using genetic mouse models of CYP8B1 overexpression, knockdown, and knockout, we demonstrated that overexpression of CYP8B1 dampened the metabolic improvements associated with VSG. In contrast, short hairpin RNA-mediated CYP8B1 knockdown improved metabolism similar to those observed after VSG. Cyp8b1 deficiency diminished the metabolic effects of VSG. Further, VSG-induced alterations to the 12&#x3b1;-OH/non-12&#x3b1;-OH BA ratio in the BA pool depended on CYP8B1 expression level. Consequently, intestinal lipid absorption was restricted, and the gut microbiota (GM) profile was altered. Fecal microbiota transplantation from wild type-VSG mice (vs. fecal microbiota transplantation from wild-type-sham mice) improved metabolism in recipient mice, while there were no differences between mice that received fecal microbiota transplantation from knockout-sham and knockout-VSG mice.<br><br>CONCLUSIONS: CYP8B1 is a critical downstream target of VSG. Modulation of BA composition and gut microbiota profile by targeting CYP8B1 may provide novel insight into the development of therapies that noninvasively mimic bariatric surgery to treat obesity and its complications.}, }
@article {pmid37819130, year = {2023}, author = {Van Den Ham, KM and Little, MR and Bednarski, OJ and Fusco, EM and Mandal, RK and Mitra, R and Li, S and Doumbo, S and Doumtabe, D and Kayentao, K and Ongoiba, A and Traore, B and Crompton, PD and Schmidt, NW}, title = {Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota.}, journal = {Microbiology spectrum}, volume = {11}, number = {6}, pages = {e0155423}, pmid = {37819130}, issn = {2165-0497}, support = {R01 AI148525/AI/NIAID NIH HHS/United States ; T32 GM148382/GM/NIGMS NIH HHS/United States ; R01 AI148525/AI/NIAID NIH HHS/United States ; }, mesh = {Child ; Humans ; Animals ; Mice ; *Intestines ; Disease Models, Animal ; Germ-Free Life ; *Gastrointestinal Microbiome ; Feces ; }, abstract = {There is increasing evidence that microbes residing within the intestines (gut microbiota) play important roles in the well-being of humans. Yet, there are considerable challenges in determining the specific role of gut microbiota in human diseases owing to the complexity of diverse internal and environmental factors that can contribute to diseases. Mice devoid of all microorganisms (germ-free mice) can be colonized with human stool samples to examine the specific contribution of the gut microbiota to a disease. These approaches have been primarily focused on stool samples obtained from individuals in Western countries. Thus, there is limited understanding as to whether the same methods used to colonize germ-free mice with stool from Western individuals would apply to the colonization of germ-free mice with stool from non-Western individuals. Here, we report the results from colonizing germ-free mice with stool samples of Malian children.}, }
@article {pmid37818040, year = {2023}, author = {Zhan, X and Zuo, Q and Huang, G and Qi, Z and Wang, Y and Zhu, S and Zhong, Y and Xiong, Y and Chen, T and Tan, B}, title = {Tripterygium glycosides sensitizes cisplatin chemotherapeutic potency by modulating gut microbiota in epithelial ovarian cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1236272}, pmid = {37818040}, issn = {2235-2988}, mesh = {Humans ; Mice ; Female ; Animals ; Cisplatin/pharmacology/therapeutic use ; Tripterygium ; Glycosides/pharmacology/therapeutic use ; Carcinoma, Ovarian Epithelial/drug therapy ; *Gastrointestinal Microbiome ; *Ovarian Neoplasms/drug therapy ; Anti-Bacterial Agents/pharmacology/therapeutic use ; }, abstract = {Epithelial ovarian cancer (EOC) is a fatal gynecological malignancy with limited therapeutic options. Previous research has demonstrated that Tripterygium glycosides (GTW) can enhance effectiveness of cisplatin (DDP) chemotherapy against EOC. However, the underlying mechanism of GTW alleviating EOC still remains unclear. In this article, an ID8 cell-derived xenograft mouse model was established to evaluate the anti-tumor efficacy of GTW combined with DDP. Consistent with previous findings, the results suggested that GTW combined with DDP can exhibit a stronger tumor suppressive effect than DDP alone. Additionally, GTW was found can further exert gastrointestinal protection against DDP by reducing pathological damage on colon tissue. Secondly, to verify whether gut microbiota play an instrumental role in GTW's anticancer effect, we treated mice models with antibiotic to eliminate gut microbiota. And our experimental results indicated that all drug groups showed a weaker tumor suppressive effect and more severe gastrointestinal damage post antibiotic supplement. At genus level, the relative abundance of Lactobacillus was dramatically diminished by the antibiotic treatment, while combined treatment of GTW and DDP can significantly restore the level. Moreover, we performed Lactobacillus acidophilus transplantation and healthy mice fecal microbiota transplantation experiments to further investigate the link between the anticancer effect of GTW and gut microbiota. Our results suggested that both cisplatin-sensitizing and intestinal barrier-protecting effects of GTW can be recovered to a different extent. In conclusion, our results indicated that GTW is a promising chemosensitization and intestinal barrier repair drug for EOC, and the potential mechanism may corelate with the restoration of the compromised intestinal microbial balance.}, }
@article {pmid37815701, year = {2023}, author = {Emile, SH and Horesh, N and Freund, MR and Garoufalia, Z and Gefen, R and Khan, SM and Silva-Alvarenga, E and Wexner, SD}, title = {A Systematic Review and Meta-analysis of Randomized Clinical Trials on the Prevention and Treatment of Pouchitis after Ileoanal Pouch Anastomosis.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {27}, number = {11}, pages = {2650-2660}, pmid = {37815701}, issn = {1873-4626}, mesh = {Humans ; *Pouchitis/etiology/prevention &amp; control ; Metronidazole/adverse effects ; *Colitis, Ulcerative/surgery ; Randomized Controlled Trials as Topic ; *Proctocolectomy, Restorative/adverse effects ; Ciprofloxacin/therapeutic use ; Anastomosis, Surgical/adverse effects ; }, abstract = {BACKGROUND: This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA).<br><br>METHODS: PubMed, Scopus, and Web of Science were searched for randomized clinical trials that assessed prevention or treatment of pouchitis. The systematic review was reported in line with updated 2020 PRISMA guidelines. Risk of bias in the trials included was assessed using the&#xa0;ROB-2 tool and certainty of evidence was assessed using GRADE. The main outcomes were the&#xa0;incidence of new pouchitis episodes in the preventative studies and resolution or improvement of active pouchitis in the treatment studies.<br><br>RESULTS: Fifteen randomized trials were included. A meta-analysis of 7 trials on probiotics revealed significantly lower odds of pouchitis with the use of probiotics (RR: 0.26, 95% CI: 0.16-0.42, I[2]&#x2009;=&#x2009;20%, p&#x2009;<&#x2009;0.001) and&#xa0;similar odds of adverse effects to placebo (RR: 2.43, 95% CI: 0.11-55.9, I[2]&#x2009;=&#x2009;0, p&#x2009;=&#x2009;0.579). One trial investigated the prophylactic role of allopurinol in preventing pouchitis and found a comparable incidence of pouchitis in the two groups (31% vs 28%; p&#x2009;=&#x2009;0.73). Seven trials assessed different treatments for active pouchitis. One recorded the resolution of pouchitis in all patients treated with ciprofloxacin versus 67% treated with metronidazole. Both budesonide enema and oral metronidazole were associated with similar significant improvement in pouchitis (58.3% vs 50%, p&#x2009;=&#x2009;0.67). Rifaximin, adalimumab, fecal microbiota transplantation, and bismuth carbomer foam enema were not effective in treating pouchitis.<br><br>CONCLUSIONS: Probiotics are effective in preventing pouchitis after IPAA. Antibiotics, including ciprofloxacin and metronidazole, are likely effective in treating active pouchitis.}, }
@article {pmid37814565, year = {2023}, author = {Korpak, K and Defourny, L and Lali, S and Delvallée, M and Demeester, R and Toussaint, E}, title = {Treatment of recurrent Clostridioides difficile infections with faecal microbiota transplantation: peri-procedural methods in a consecutive case series.}, journal = {Acta gastro-enterologica Belgica}, volume = {86}, number = {3}, pages = {486-489}, doi = {10.51821/86.3.11795}, pmid = {37814565}, issn = {1784-3227}, mesh = {Humans ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation/methods ; Feces ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has high efficacy against recurrent Clostridioides difficile infection (CDI). Despite the increasing use of this therapy, the delay between diagnosis and treatment is excessive. Furthermore, donor selection is an important and time-consuming process.<br><br>METHODS: We reviewed patients who underwent FMT for recurrent CDI at the CHU Charleroi Hospital between 2015 and 2022. The general context, type of administration, adverse events, and donor selection were reported. FMT was conducted using gastroduodenoscopy, colonoscopy, and enema with either fresh or frozen material.<br><br>RESULTS: Ten patients with multiple comorbidities were treated by FMT. Seven patients were cured after one procedure. One patient was successfully cured after a change to an unrelated donor, and preliminary efficacy was established.<br><br>CONCLUSIONS: FMT is an effective treatment that should be considered during the earlier phases of treatment. Stool donors should be thoroughly screened for infectious diseases and other criteria related to microbiota composition.}, }
@article {pmid37814439, year = {2023}, author = {Zhang, J and Zhang, C and Zhang, T and Zhang, L and Duan, L}, title = {Distinct Effects of Non-absorbed Agents Rifaximin and Berberine on the Microbiota-Gut-Brain Axis in Dysbiosis-induced Visceral Hypersensitivity in Rats.}, journal = {Journal of neurogastroenterology and motility}, volume = {29}, number = {4}, pages = {520-531}, pmid = {37814439}, issn = {2093-0879}, abstract = {BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is accepted as a disorder of gut-brain interactions. Berberine and rifaximin are non-absorbed antibiotics and have been confirmed effective for IBS treatment, but there is still lack of direct comparison of their effects. This study aims to compare the effect of the 2 drugs on the alteration of gut-brain axis caused by gut microbiota from IBS patients.<br><br>METHODS: Germ-free rats received fecal microbiota transplantation from screened IBS patients and healthy controls. After 14 days' colonization, rats were administrated orally with berberine, rifaximin or vehicle respectively for the next 14 days. The visceral sensitivity was evaluated, fecal microbiota profiled and microbial short chain fatty acids were determined. Immunofluorescence staining and morphological analysis were performed to evaluate microglial activation.<br><br>RESULTS: Visceral hypersensitivity induced by IBS-fecal microbiota transplantation was relieved by berberine and rifaximin, and berberine increased sucrose preference rate. Microbial &#x3b1;-diversity were reduced by both drugs. Compared with rifaximin, berberine significantly changed microbial structure and enriched Lachnoclostridium. Furthermore, berberine but not rifaximin significantly increased fecal concentrations of acetate and propionate acids. Berberine restored the morphological alterations of microglia induced by dysbiosis, which may be associated with its effect on the expression of microbial gene pathways involved in peptidoglycan biosynthesis. Rifaximin affected neither the numbers of activated microglial cells nor the microglial morphological alterations.<br><br>CONCLUSIONS: Berberine enriched Lachnoclostridium, reduced the expression of peptidoglycan biosynthesis genes and increased acetate and propionate. The absence of these actions of rifaximin may explain the different effects of the drugs on microbiota-gut-brain axis.}, }
@article {pmid37813835, year = {2023}, author = {Han, D and Wu, Y and Lu, D and Pang, J and Hu, J and Zhang, X and Wang, Z and Zhang, G and Wang, J}, title = {Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation.}, journal = {Cell death &amp; disease}, volume = {14}, number = {10}, pages = {656}, pmid = {37813835}, issn = {2041-4889}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Polyphenols/pharmacology/metabolism ; Neutrophils/metabolism ; Ellagic Acid/metabolism/pharmacology ; *Colitis/metabolism ; Inflammation/pathology ; Diet ; Macrophages/metabolism ; Dextran Sulfate/toxicity ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/pathology ; }, abstract = {Dietary phenolic acids alleviate intestinal inflammation through altering gut microbiota composition and regulating macrophage activation. However, it is unclear how individual phenolic acids affect the interactions between intestinal microbiota and macrophages in the context of inflammatory bowel disease (IBD). Here, we aim to elucidate the mechanism by which phenolic acids alleviate gut inflammation. Mice with or without depletion of macrophages were administered with four individual phenolic acids including chlorogenic, ferulic, caffeic, and ellagic acids, following dextran sulfate sodium (DSS) treatment. Gut microbiota depletion and fecal microbiota transplantation were further performed in mice to investigate the role of the gut microbiota in phenolic acid-mediated protective effect. Colitis severity was evaluated using histological, serological, and immunological measurements. Absence of intestinal microbiota and macrophage deteriorate the epithelial injury in DSS colitis. Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation. However, ferulic acid-mediated reduction of colitis was neutrophil-dependent through diminishing the formation of neutrophil extracellular traps. On the other hand, the beneficial effects of caffeic acid and ellagic acid were dependent upon the gut microbiota. In fact, urolithin A (UroA), a metabolite transformed from ellagic acid by the gut microbiota, was found to alleviate colitis and enhance gut barrier function in an IL22-dependent manner. Overall, our findings demonstrated that the mechanisms by which phenolic acid protected against colitis were resulted from the interaction between gut microbiota and macrophage-neutrophil.}, }
@article {pmid37809261, year = {2023}, author = {Masood, L and Müller, A and Ali, NZ and Mummadisetty, A and Yahya, A and Burugu, SS and Sajid, R and Lakkimsetti, M and Sagireddy, S and Abdin, ZU and Nazir, Z}, title = {A Narrative Literature Review on Sepsis: A Primary Manifestation of Colorectal Neoplasm.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e44803}, pmid = {37809261}, issn = {2168-8184}, abstract = {Sepsis and colorectal cancer (CRC) exhibit a complex relationship that warrants further exploration. This review delves into the interplay of factors between sepsis and CRC, uncovering shared pathophysiological traits and potential bacterial associations. Understanding these connections could pave the way for earlier diagnosis, improved management, and enhanced outcomes in CRC patients. The role of immune system dysfunction, hypoalbuminemia, and specific microbial imbalances, such as Streptococcus bovis and Clostridium septicum, are discussed. Recognizing sepsis in CRC patients is crucial for timely intervention, and tailored approaches encompassing antibiotic therapy, source control measures, and cancer treatment are essential for comprehensive care. Monitoring biomarkers and ratios can provide valuable insights into complications and overall health outcomes. A multidisciplinary approach involving various specialists is necessary to address the global burden of CRC and its association with sepsis while exploring novel interventions, such as fecal microbiota transplantation and personalized care. We conducted a thorough search using reputable databases such as PubMed, Scopus, and Google Scholar to investigate the connection between sepsis and CRC. We refined our search terms, utilized sidebar filters, and examined references in selected articles. This meticulous process helped us create a comprehensive literature review and gain valuable insights into this relationship.}, }
@article {pmid37807005, year = {2023}, author = {Arjomand Fard, N and Bording-Jorgensen, M and Wine, E}, title = {A Potential Role for Gut Microbes in Mediating Effects of Omega-3 Fatty Acids in Inflammatory Bowel Diseases: A Comprehensive Review.}, journal = {Current microbiology}, volume = {80}, number = {11}, pages = {363}, pmid = {37807005}, issn = {1432-0991}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy/microbiology ; Bacteria/genetics ; Fecal Microbiota Transplantation ; *Fatty Acids, Omega-3 ; }, abstract = {Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with several inflammatory conditions, including inflammatory bowel diseases (IBDs), and found to have an impact on gut microbiota. In fact, some randomized controlled studies suggest benefits to IBD patients, but others do not. Our aim was to review recent evidence on the effects of omega-3 on IBD and establish the contribution of the gut microbiome. Omega-3 mediate anti-inflammatory effects in IBD through various mechanisms, including suppression of NLR family pyrin domain-containing 3 (NLRP3) inflammasome, Toll-like receptor-4 (TLR4), and nucleotide-binding oligomerization domain 2 (NOD2) signaling; this results in the repression of the nuclear factor-kappa B (Nf-kB) pathway and the secretion of pro-inflammatory cytokines. Omega-3 can also affect gut microbiota and revert the bacterial community to patterns associated with healthy status by increasing short-chain fatty acid (SCFA)-producing bacteria and enhancing the mucosal gut barrier, thus promoting homeostasis. The combination of these immunoregulatory effects and anti-inflammation properties with the promotion of a balanced gut microbiome environment could suggest that omega-3 might benefit IBD patients. Considering the microbiota of IBD patients while using omega-3 might predict and improve omega-3 effectiveness. Combining omega-3 with bacteria-altering therapy, such as probiotics and fecal microbiota transplantation, may further enhance its efficacy; however, further studies are required to elucidate mechanisms and potential preventive or treatment roles of omega-3 in IBD.}, }
@article {pmid37806386, year = {2023}, author = {Kumbhare, SV and Pedroso, I and Ugalde, JA and Márquez-Miranda, V and Sinha, R and Almonacid, DE}, title = {Drug and gut microbe relationships: Moving beyond antibiotics.}, journal = {Drug discovery today}, volume = {28}, number = {11}, pages = {103797}, doi = {10.1016/j.drudis.2023.103797}, pmid = {37806386}, issn = {1878-5832}, mesh = {*Gastrointestinal Microbiome ; Anti-Bacterial Agents/pharmacology ; *Probiotics ; }, abstract = {Our understanding of drug-microbe relationships has evolved from viewing microbes as mere drug producers to a dynamic, modifiable system where they can serve as drugs or targets of precision pharmacology. This review highlights recent findings on the gut microbiome, particularly focusing on four aspects of research: (i) drugs for bugs, covering recent strategies for targeting gut pathogens; (ii) bugs as drugs, including probiotics; (iii) drugs from bugs, including postbiotics; and (iv) bugs and drugs, discussing additional types of drug-microbe interactions. This review provides a perspective on future translational research, including efficient companion diagnostics in pharmaceutical interventions.}, }
@article {pmid37806074, year = {2023}, author = {Pötgens, SA and Lecop, S and Havelange, V and Li, F and Neyrinck, AM and Neveux, N and Maertens, J and Walter, J and Schoemans, H and Delzenne, NM and Bindels, LB}, title = {Gut microbiota alterations induced by intensive chemotherapy in acute myeloid leukaemia patients are associated with gut barrier dysfunction and body weight loss.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {42}, number = {11}, pages = {2214-2228}, doi = {10.1016/j.clnu.2023.09.021}, pmid = {37806074}, issn = {1532-1983}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Cachexia ; Weight Loss ; Metabolomics ; *Leukemia, Myeloid, Acute/drug therapy ; }, abstract = {BACKGROUND &amp; AIMS: Acute myeloid leukaemia (AML) chemotherapy has been reported to impact gut microbiota composition. In this study, we investigated using a multi -omics strategy the changes in the gut microbiome induced by AML intense therapy and their association with gut barrier function and cachectic hallmarks.<br><br>METHODS: 10 AML patients, allocated to standard induction chemotherapy (SIC), were recruited. Samples and data were collected before any therapeutic intervention (T0), at the end of the SIC (T1) and at discharge (T4). Gut microbiota composition and function, markers of inflammation, metabolism, gut barrier function and cachexia, as well as faecal, blood and urine metabolomes were assessed.<br><br>RESULTS: AML patients demonstrated decreased appetite, weight loss and muscle wasting during hospitalization, with an incidence of cachexia of 50%. AML intensive treatment transiently impaired the gut barrier function and led to a long-lasting change of gut microbiota composition characterized by an important loss of diversity. Lactobacillaceae and Campylobacter concisus were increased at T1 while Enterococcus faecium and Staphylococcus were increased at T4. Metabolomics analyses revealed a reduction in urinary hippurate and faecal bacterial amino acid metabolites (bAAm) (2-methylbutyrate, isovalerate, phenylacetate). Integration using DIABLO revealed a deep interconnection between all the datasets. Importantly, we identified bacteria which disappearance was associated with impaired gut barrier function (Odoribacter splanchnicus) and body weight loss (Gemmiger formicilis), suggesting these bacteria as actionable targets.<br><br>CONCLUSION: AML intensive therapy transiently impairs the gut barrier function while inducing enduring alterations in the composition and metabolic activity of the gut microbiota that associate with body weight loss.<br><br>TRIAL REGISTRATION: NCT03881826, https://clinicaltrials.gov/ct2/show/NCT03881826.}, }
@article {pmid37805634, year = {2023}, author = {Peña-Cearra, A and Song, D and Castelo, J and Palacios, A and Lavín, JL and Azkargorta, M and Elortza, F and Fuertes, M and Pascual-Itoiz, MA and Barriales, D and Martín-Ruiz, I and Fullaondo, A and Aransay, AM and Rodríguez, H and Palm, NW and Anguita, J and Abecia, L}, title = {Mitochondrial dysfunction promotes microbial composition that negatively impacts on ulcerative colitis development and progression.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {74}, pmid = {37805634}, issn = {2055-5008}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; *Colitis, Ulcerative/genetics/microbiology ; RNA, Ribosomal, 16S/genetics ; *Colitis ; *Inflammatory Bowel Diseases ; Immunoglobulin A ; Mitochondria/genetics ; Disease Progression ; }, abstract = {Recent evidence demonstrates potential links between mitochondrial dysfunction and inflammatory bowel diseases (IBD). In addition, bidirectional interactions between the intestinal microbiota and host mitochondria may modulate intestinal inflammation. We observed previously that mice deficient in the mitochondrial protein MCJ (Methylation-controlled J protein) exhibit increased susceptibility to DSS colitis. However, it is unclear whether this phenotype is primarily driven by MCJ[-/-] associated gut microbiota dysbiosis or by direct effects of MCJ-deficiency. Here, we demonstrate that fecal microbiota transplantation (FMT) from MCJ-deficient into germ-free mice was sufficient to confer increased susceptibility to colitis. Therefore, an FMT experiment by cohousing was designed to alter MCJ-deficient microbiota. The phenotype resulting from complex I deficiency was reverted by FMT. In addition, we determined the protein expression pathways impacted by MCJ deficiency, providing insight into the pathophysiology of IBD. Further, we used magnetic activated cell sorting (MACS) and 16S rRNA gene sequencing to characterize taxa-specific coating of the intestinal microbiota with Immunoglobulin A (IgA-SEQ) in MCJ-deficient mice. We show that high IgA coating of fecal bacteria observed in MCJ-deficient mice play a potential role in disease progression. This study allowed us to identify potential microbial signatures in feces associated with complex I deficiency and disease progression. This research highlights the importance of finding microbial biomarkers, which might serve as predictors, permitting the stratification of ulcerative colitis (UC) patients into distinct clinical entities of the UC spectrum.}, }
@article {pmid37802720, year = {2024}, author = {Portincasa, P and Khalil, M and Graziani, A and Frühbeck, G and Baffy, G and Garruti, G and Di Ciaula, A and Bonfrate, L}, title = {Gut microbes in metabolic disturbances. Promising role for therapeutic manipulations?.}, journal = {European journal of internal medicine}, volume = {119}, number = {}, pages = {13-30}, doi = {10.1016/j.ejim.2023.10.002}, pmid = {37802720}, issn = {1879-0828}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 2 ; Obesity/therapy/microbiology ; *Metabolic Syndrome/therapy ; *Fatty Liver ; Inflammation ; }, abstract = {The prevalence of overweight, obesity, type 2 diabetes, metabolic syndrome and steatotic liver disease is rapidly increasing worldwide with a huge economic burden in terms of morbidity and mortality. Several genetic and environmental factors are involved in the onset and development of metabolic disorders and related complications. A critical role also exists for the gut microbiota, a complex polymicrobial ecology at the interface of the internal and external environment. The gut microbiota contributes to food digestion and transformation, caloric intake, and immune response of the host, keeping the homeostatic control in health. Mechanisms of disease include enhanced energy extraction from the non-digestible dietary carbohydrates, increased gut permeability and translocation of bacterial metabolites which activate a chronic low-grade systemic inflammation and insulin resistance, as precursors of tangible metabolic disorders involving glucose and lipid homeostasis. The ultimate causative role of gut microbiota in this respect remains to be elucidated, as well as the therapeutic value of manipulating the gut microbiota by diet, pre- and pro- synbiotics, or fecal microbial transplantation.}, }
@article {pmid37802272, year = {2024}, author = {Jangi, S and Hsia, K and Zhao, N and Kumamoto, CA and Friedman, S and Singh, S and Michaud, DS}, title = {Dynamics of the Gut Mycobiome in Patients With Ulcerative Colitis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {22}, number = {4}, pages = {821-830.e7}, pmid = {37802272}, issn = {1542-7714}, support = {KL2 TR002545/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Humans ; *Colitis, Ulcerative/pathology ; *Mycobiome ; Prospective Studies ; *Crohn Disease/complications ; *Inflammatory Bowel Diseases/complications ; Feces/microbiology ; }, abstract = {BACKGROUND &amp; AIMS: Intestinal fungi have been implicated in the pathogenesis of ulcerative colitis (UC). However, it remains unclear if fungal composition is altered during active versus quiescent disease.<br><br>METHODS: We analyzed clinical and metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn's &amp; Colitis Foundation. We evaluated the fungal composition of fecal samples from 421 patients with UC during clinical activity and remission. Within a longitudinal subcohort (n&#xa0;= 52), we assessed for dynamic taxonomic changes across alterations in clinical activity over time. We examined if fungal amplicon sequence variants and fungal-bacterial relationships were altered during activity versus remission. Finally, we classified activity in UC using a supervised machine learning random forest model trained on fungal abundance data.<br><br>RESULTS: During clinical activity, the relative abundance of genus Candida was increased 3.5-fold (P-adj < 1&#xa0;&#xd7; 10[-4]) compared with during remission. Patients with longitudinal reductions in clinical activity demonstrated parallel reductions in Candida relative abundance (P < .05). Candida relative abundance correlated with Parabacteroides diastonis, Faecalibacterium prausnitzii, and Bacteroides dorei relative abundance (P < .05) during remission; however, these correlations were disrupted during activity. Fungal abundance data successfully classified patients with active or quiescent UC (area under the curve &#x223c;0.80), with Candida relative abundance critical to the success of the model.<br><br>CONCLUSIONS: Clinical activity in UC is associated with an increased relative abundance of Candida, cross-sectionally and dynamically over time. The role of fecal Candida as a target for therapeutics in UC should be evaluated.}, }
@article {pmid37800288, year = {2023}, author = {Hosonuma, M and Murayama, M and Yoshimura, K}, title = {[The Gut Microbiota Metabolite A Enhances the Anti-Tumor Effects of Anti-PD-1 Antibody Therapy through Immune Modulation].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {50}, number = {9}, pages = {960-964}, pmid = {37800288}, issn = {0385-0684}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics ; *Inflammatory Bowel Diseases/therapy ; *Neoplasms/therapy ; }, abstract = {The gut microbiota is an important partner in humans, and its dysregulation is associated with the development of inflammatory bowel diseases and cancer. Furthermore, the gut microbiota is involved in the therapeutic effects of immune checkpoint inhibitors, and controlling the gut microbiota may enhance the efficacy of cancer immunotherapy. Currently, the development of therapies to control the gut microbiota includes fecal transplantation, probiotics, prebiotics, and postbiotics. In this article, we introduce SCFA-A, a type of short-chain fatty acid(SCFA)and a metabolite of gut microbiota, which is involved in the activation of T cells and induction of M1 macrophages, thereby enhancing the anti-tumor effects of anti- PD-1 antibody therapy. SCFA-A holds promise as a novel treatment approach in cancer immunotherapy as a postbiotic.}, }
@article {pmid37798771, year = {2023}, author = {Zhou, C and Li, J and Guo, C and Zhou, Z and Yang, Z and Zhang, Y and Jiang, J and Cai, Y and Zhou, J and Xia, M and Ming, Y}, title = {Alterations in gut microbiome and metabolite profile of patients with Schistosoma japonicum infection.}, journal = {Parasites &amp; vectors}, volume = {16}, number = {1}, pages = {346}, pmid = {37798771}, issn = {1756-3305}, support = {81771722//National Natural Science Foundation of China/ ; 2021SK2032//Key Research and Development Plan of Hunan Province/ ; }, mesh = {Animals ; Humans ; *Schistosomiasis japonica/genetics ; *Gastrointestinal Microbiome ; *Schistosoma japonicum ; *Schistosomiasis/diagnosis ; China ; }, abstract = {BACKGROUND: Schistosoma infection is a significant public health issue, affecting over 200 million individuals and threatening 700 million people worldwide. The species prevalent in China is Schistosoma japonicum. Recent studies showed that both gut microbiota and metabolome are closely related to schistosomiasis caused by S. japonicum, but clinical study is limited and the underlying mechanism is largely unclear. This study aimed to explore alterations as well as function of gut microbiota and metabolite profile in the patients with S. japonicum infection.<br><br>METHODS: This study included 20 patients diagnosed with chronic schistosomiasis caused by S. japonicum, eight patients with advanced schistosomiasis caused by S. japonicum and 13 healthy volunteers. The fresh feces of these participators, clinical examination results and basic information were collected. 16S ribosomal RNA gene sequencing was used to investigate gut microbiota, while ultraperformance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to explore the metabolome of patients in different stages of schistosomiasis.<br><br>RESULTS: The study found that gut microbiota and metabolites were altered in patients with different stages of S. japonicum infection. Compared with healthy control group, the gut microbial diversity in patients with chronic S. japonicum infection was decreased significantly. However, the diversity of gut microbiota in patients with chronic schistosomiasis was similar to that in patients with advanced schistosomiasis. Compared with uninfected people, patients with schistosomiasis showed decreased Firmicutes and increased Proteobacteria. As disease progressed, Firmicutes was further reduced in patients with advanced S. japonicum infection, while Proteobacteria was further increased. In addition, the most altered metabolites in patients with S. japonicum infection were lipids and lipid-like molecules as well as organo-heterocyclic compounds, correlated with the clinical manifestations and disease progress of schistosomiasis caused by S. japonicum.<br><br>CONCLUSIONS: This study suggested that the gut microbiota and metabolome altered in patients in different stages of schistosomiasis, which was correlated with progression of schistosomiasis caused by S. japonicum. This inter-omics analysis may shed light on a better understanding of the mechanisms of the progression of S. japonicum infection and contribute to identifying new potential targets for the diagnosis and prognosis of S. japonicum infection. However, a large sample size of validation in clinic is needed, and further study is required to investigate the underlying mechanism.}, }
@article {pmid37798034, year = {2023}, author = {Vendrik, KE and Chernova, VO and Kuijper, EJ and Terveer, EM and van Hilten, JJ and Contarino, MF and , }, title = {Safety and feasibility of faecal microbiota transplantation for patients with Parkinson's disease: a protocol for a self-controlled interventional donor-FMT pilot study.}, journal = {BMJ open}, volume = {13}, number = {10}, pages = {e071766}, pmid = {37798034}, issn = {2044-6055}, mesh = {Humans ; Feasibility Studies ; *Fecal Microbiota Transplantation/adverse effects/methods ; Feces ; Levodopa ; *Parkinson Disease/therapy/etiology ; Pilot Projects ; Prospective Studies ; Treatment Outcome ; }, abstract = {INTRODUCTION: Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson's disease (PD) via the gut-brain axis. The gut microbiota can also influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by faecal microbiota transplantation (FMT) could be a supportive treatment strategy.<br><br>METHODS AND ANALYSIS: We have developed a study protocol for a single-centre, prospective, self-controlled, interventional, safety and feasibility donor-FMT pilot study with randomisation and double-blinded allocation of donor faeces. The primary objectives are feasibility and safety of FMT in patients with PD. Secondary objectives include exploring whether FMT leads to alterations in motor complications (fluctuations and dyskinesias) and PD motor and non-motor symptoms (including constipation), determining alterations in gut microbiota composition, assessing donor-recipient microbiota similarities and their association with PD symptoms and motor complications, evaluating the ease of the study protocol and examining FMT-related adverse events in patients with PD. The study population will consist of 16 patients with idiopathic PD that use levodopa and experience motor complications. They will receive FMT with faeces from one of two selected healthy human donors. FMT will be administered via a gastroscope into the duodenum, after treatment with oral vancomycin, bowel lavage and domperidone. There will be seven follow-up moments during 12 months.<br><br>ETHICS AND DISSEMINATION: This study was approved by the Medical Ethical Committee Leiden Den Haag Delft (ref. P20.087). Study results will be disseminated through publication in peer-reviewed journals and international conferences.<br><br>TRIAL REGISTRATION NUMBER: International Clinical Trial Registry Platform: NL9438.}, }
@article {pmid37797200, year = {2023}, author = {Han, Q and Liu, R and Wang, H and Zhang, R and Liu, H and Li, J and Bao, J}, title = {Gut Microbiota-Derived 5-Hydroxyindoleacetic Acid Alleviates Diarrhea in Piglets via the Aryl Hydrocarbon Receptor Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {41}, pages = {15132-15144}, doi = {10.1021/acs.jafc.3c04658}, pmid = {37797200}, issn = {1520-5118}, mesh = {Swine ; Animals ; Female ; *Gastrointestinal Microbiome ; Hydroxyindoleacetic Acid ; Receptors, Aryl Hydrocarbon/genetics ; Diarrhea/therapy/veterinary/microbiology ; Cytokines/genetics ; }, abstract = {With the improvement in sow prolificacy, formula feeding has been increasingly used in the pig industry. Diarrhea remains a serious health concern in formula-fed (FF) piglets. Fecal microbiota transplantation (FMT) is an efficacious strategy to reshape gut microbiota and the metabolic profile for treating diarrhea. This study aims to investigate whether FMT from breast-fed piglets could alleviate diarrhea in FF piglets. The piglets were randomly assigned to the control (CON) group, FF group, and FMT group. Our results showed that FF piglets exhibited a higher diarrhea incidence, damaged colonic morphology, and disrupted barrier function. In contrast, FMT treatment normalized the morphology and barrier function. FMT suppressed the JNK/MAPK pathway and production of proinflammatory cytokines. Additionally, FF piglets had a lower abundance of the beneficial bacterial genus Bifidobacterium compared to CON piglets. Following FMT administration, Bifidobacterium was restored. Meanwhile, 5-HIAA, a metabolite of tryptophan, and AHR-responsive CYP1A1 and CYP1B1 were upregulated. Importantly, integrated multiomics analysis revealed a strong positive correlation between Bifidobacterium and 5-HIAA. In vitro, 5-HIAA supplementation reversed the LPS-induced disruption of tight junctions and production of proinflammatory cytokines in IPEC-J2 cells. In conclusion, FMT reduced diarrhea incidence and improved growth performance. The alleviative effect of FMT on diarrhea was associated with Bifidobacterium and 5-HIAA.}, }
@article {pmid37796494, year = {2023}, author = {Stewart, AK and Foley, MH and Dougherty, MK and McGill, SK and Gulati, AS and Gentry, EC and Hagey, LR and Dorrestein, PC and Theriot, CM and Dodds, JN and Baker, ES}, title = {Using Multidimensional Separations to Distinguish Isomeric Amino Acid-Bile Acid Conjugates and Assess Their Presence and Perturbations in Model Systems.}, journal = {Analytical chemistry}, volume = {95}, number = {41}, pages = {15357-15366}, pmid = {37796494}, issn = {1520-6882}, support = {RM1 GM145416/GM/NIGMS NIH HHS/United States ; P42 ES031009/ES/NIEHS NIH HHS/United States ; R01 DK136117/DK/NIDDK NIH HHS/United States ; R01 GM141277/GM/NIGMS NIH HHS/United States ; P42 ES027704/ES/NIEHS NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; T32 DK007634/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; *Bile Acids and Salts ; *Amino Acids ; Isomerism ; Mass Spectrometry ; Steroids ; }, abstract = {Bile acids play key roles in nutrient uptake, inflammation, signaling, and microbiome composition. While previous bile acid analyses have primarily focused on profiling 5 canonical primary and secondary bile acids and their glycine and taurine amino acid-bile acid (AA-BA) conjugates, recent studies suggest that many other microbial conjugated bile acids (or MCBAs) exist. MCBAs are produced by the gut microbiota and serve as biomarkers, providing information about early disease onset and gut health. Here we analyzed 8 core bile acids synthetically conjugated with 22 proteinogenic and nonproteogenic amino acids totaling 176 MCBAs. Since many of the conjugates were isomeric and only 42 different m/z values resulted from the 176 MCBAs, a platform coupling liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) was used for their separation. Their molecular characteristics were then used to create an in-house extended bile acid library for a combined total of 182 unique compounds. Additionally, ∼250 rare bile acid extracts were also assessed to provide additional resources for bile acid profiling and identification. This library was then applied to healthy mice dosed with antibiotics and humans having fecal microbiota transplantation (FMT) to assess the MCBA presence and changes in the gut before and after each perturbation.}, }
@article {pmid37796016, year = {2023}, author = {Kamer, O and Rinott, E and Tsaban, G and Kaplan, A and Yaskolka Meir, A and Zelicha, H and Knights, D and Tuohy, K and Fava, F and Uwe Scholz, M and Ziv, O and Rubin, E and Blüher, M and Stumvoll, M and Ceglarek, U and Clément, K and Koren, O and Hu, FB and Stampfer, MJ and Wang, DD and Youngster, I and Shai, I}, title = {Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2264457}, pmid = {37796016}, issn = {1949-0984}, support = {R00 DK119412/DK/NIDDK NIH HHS/United States ; R01 AG077489/AG/NIA NIH HHS/United States ; R01 NR019992/NR/NINR NIH HHS/United States ; }, mesh = {Humans ; Middle Aged ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Feces ; Weight Loss ; Weight Gain ; }, abstract = {We previously reported that autologous-fecal-microbiota-transplantation (aFMT), following 6 m of lifestyle intervention, attenuated subsequent weight regain and insulin rebound for participants consuming a high-polyphenol green-Mediterranean diet. Here, we explored whether specific changes in the core (abundant) vs. non-core (low-abundance) gut microbiome taxa fractions during the weight-loss phase (0-6 m) were differentially associated with weight maintenance following aFMT. Eighty-two abdominally obese/dyslipidemic participants (age = 52 years; 6 m weightloss = -8.3 kg) who provided fecal samples (0 m, 6 m) were included. Frozen 6 m's fecal samples were processed into 1 g, opaque and odorless aFMT capsules. Participants were randomly assigned to receive 100 capsules containing their own fecal microbiota or placebo over 8 m-14 m in ten administrations (adherence rate > 90%). Gut microbiome composition was evaluated using shotgun metagenomic sequencing. Non-core taxa were defined as ≤ 66% prevalence across participants. Overall, 450 species were analyzed. At baseline, 13.3% were classified as core, and Firmicutes presented the highest core proportion by phylum. During 6 m weight-loss phase, abundance of non-core species changed more than core species (P < .0001). Subject-specific changes in core and non-core taxa fractions were strongly correlated (Jaccard Index; r = 0.54; P < .001). Following aFMT treatment, only participants with a low 6 m change in core taxa, and a high change in non-core taxa, avoided 8-14 m weight regain (aFMT = -0.58 ± 2.4 kg, corresponding placebo group = 3.18 ± 3.5 kg; P = .02). In a linear regression model, low core/high non-core 6 m change was the only combination that was significantly associated with attenuated 8-14 m weight regain (P = .038; P = .002 for taxa patterns/treatment intervention interaction). High change in non-core, low-abundance taxa during weight-loss might mediate aFMT treatment success for weight loss maintenance.ClinicalTrials.gov: NCT03020186.}, }
@article {pmid37795613, year = {2023}, author = {Wang, C and Liu, XL and Sun, Q and Zhao, FY and Dai, PQ and Li, LX and Hu, DG}, title = {Apple consumption affects cecal health by regulating 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) levels through modifying the microbiota in rats.}, journal = {Food &amp; function}, volume = {14}, number = {20}, pages = {9419-9433}, doi = {10.1039/d3fo03207h}, pmid = {37795613}, issn = {2042-650X}, mesh = {Humans ; Rats ; Animals ; *Malus/metabolism ; Rats, Wistar ; Arachidonic Acids/metabolism ; Arachidonic Acid/metabolism ; Hydroxyeicosatetraenoic Acids/metabolism ; Cecum/metabolism ; }, abstract = {Apples are rich in many nutrients and functional components. However, the mechanism of the effect of fresh apple consumption on rats remains unclear. In the present study, fresh apples (10 g kg[-1]) were added to the diet of Wistar rats, and changes in the microbiota and metabolite content of the cecum were analyzed after 28 days of feeding, and changes in the 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) content and indicators related to inflammation, oxidative stress, and apoptosis were detected. Subsequently, a fecal microbiota transplantation (FMT) protocol was designed and carried out to verify the relationship between the microbiota and 12(S)-HETE, the cecal structure, and inflammatory factors. The results show that apple consumption significantly reduced the serum levels of alanine aminotransferase (ALT) and immunoglobulin G (IgG), altered the cecal histomorphology, and significantly upregulated the gene expression of claudin-1 and zonula occludens-1 (ZO-1), which encode tight junction proteins. Apple consumption also changed the structure of the cecal microbiota, increasing the abundance of some species (such as Shuttleworthia) and decreasing the abundance of others (such as Alphaproteobacteria). Metabolomic screening identified 64 significantly different metabolites. The FMT results showed that apple consumption reduced 12(S)-HETE metabolite levels in the cecal contents, improved the intestinal structure, and reduced the levels of proinflammatory factor expression by altering the cecal microbiota. In conclusion, this study provides further insight into the effects of apples on animals using rats as experimental animals. It provides basic data for future exploration of the mechanisms of the effect of apple consumption on humans.}, }
@article {pmid37795305, year = {2023}, author = {Yang, Y and Cui, B and Lv, Y and Lu, X and Shen, W and Feng, M and Ding, X and Dong, P and Wang, Y}, title = {Plateau pika fecal microbiota transplantation ameliorates inflammatory bowel disease manifestations in a mouse model of colitis.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1228778}, pmid = {37795305}, issn = {1664-302X}, abstract = {Inflammatory bowel disease (IBD) is a serious global public health concern. Although the pathogenesis of the disease is currently unknown, it has been reported to be associated with both intestinal microbiota and inflammatory mediators. There is evidence suggesting that the feces of the Plateau pika is useful for treating gastrointestinal injuries and pain. Although fecal microbiota transplantation is highly efficacious intervention for IBD prevention, however, potential the transfer of pathogenic microbes or toxic substances is potentially hazardous. Fortunately, micropore filtering of the donor feces can minimize the risk of bacterial infection allowing retention of the therapeutic effects of the residual bacteriophages. Here, we demonstrated that Plateau pika feces not only alleviated the IBD symptoms but also promoted optimal structure and composition of the intestinal microbiota. Additionally, Plateau pika feces transfer also enhanced phenotypic features, such as, body-weight, disease activity index, and histological scores. In conclusion, Plateau pika feces was found to protect mice against colitis induced by dextran sodium sulfate by reducing inflammation and regulating microbial dysbiosis. These findings suggest the potential of Plateau pika feces as an alternative therapy for IBD.}, }
@article {pmid37794047, year = {2023}, author = {Li, G and Liu, L and Lu, T and Sui, Y and Zhang, C and Wang, Y and Zhang, T and Xie, Y and Xiao, P and Zhao, Z and Cheng, C and Hu, J and Chen, H and Xue, D and Chen, H and Wang, G and Kong, R and Tan, H and Bai, X and Li, Z and McAllister, F and Li, L and Sun, B}, title = {Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {6179}, pmid = {37794047}, issn = {2041-1723}, mesh = {Bacteroides ; Interleukin-17/metabolism ; *Extracellular Traps/metabolism ; *Pancreatitis/metabolism ; Humans ; *Gastrointestinal Microbiome/physiology ; Taurine/metabolism ; Mice ; Animals ; }, abstract = {Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. Moreover, Bacteroides uniformis or taurine inhibits the activation of NF-κB and IL-17 signaling pathways in neutrophils which harness NETs and alleviate pancreatic injury. Our findings establish roles of endogenous Bacteroides uniformis-derived metabolic and inflammatory products on suppressing NETs release, which provides potential insights of ameliorating HTGP through gut microbiota modulation.}, }
@article {pmid37793354, year = {2023}, author = {Shi, X and Li, Z and Lin, W and Shi, W and Hu, R and Chen, G and Li, X and Li, X and Zhang, S}, title = {Altered Intestinal Microbial Flora and Metabolism in Patients with Idiopathic Membranous Nephropathy.}, journal = {American journal of nephrology}, volume = {54}, number = {11-12}, pages = {451-470}, doi = {10.1159/000533537}, pmid = {37793354}, issn = {1421-9670}, mesh = {Humans ; Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; *Glomerulonephritis, Membranous ; Dysbiosis ; RNA, Ribosomal, 16S/genetics ; Biomarkers ; }, abstract = {INTRODUCTION: Dysbiosis of the intestinal microbiome and related metabolites have been observed in chronic kidney disease, yet their roles in idiopathic membranous nephropathy (IMN) are poorly understood.<br><br>METHODS: In this study, we describe the variation of intestinal bacteria and fecal metabolites in patients with IMN in Chinese population. Stool samples were collected from 41 IMN patients at the beginning of diagnosis confirmation and 41 gender- and age-matched healthy control (HC). Microbial communities are investigated by sequencing of 16S rRNA genes and functional profiles predicted using Tax4Fun, and the correlation between intestinal bacteria and IMN clinical characteristics is also analyzed. Untargeted metabolomic analysis is performed to explore the relationship between colon's microbiota and fecal metabolites.<br><br>RESULTS: IMN gastrointestinal microbiota demonstrates lower richness and diversity compared to HC, and exhibits a marked taxonomic and inferred functional dysbiosis when compared to HC. Some genera are closely related to the clinical parameters, such as Citrobacter and Akkermansia. Twenty characteristic microbial biomarkers are selected to establish a disease prediction model with a diagnostic accuracy of 93.53%. Fecal metabolomics shows that tryptophan metabolism is reduced in IMN patients but uremic toxin accumulation in feces is not noticeable. Fecal microbiota transplantation demonstrates that gut dysbiosis impairs gut permeability in microbiota-depleted mice and induces NOD-like receptor activation in the kidneys.<br><br>CONCLUSIONS: Clarifying the changes in intestinal microbiota in IMN patients will help further know the pathogenesis of this disease, and microbiota-targeted biomarkers will provide a potentially powerful tool for diagnosing and treating IMN.}, }
@article {pmid37793163, year = {2024}, author = {Zhang, S and Zhao, X and Wang, X and Jin, H and Chen, L and Ma, Y and Chi, Y and Zhang, J and Zhang, J and Gao, Y}, title = {Gut Microecology May Be Involved in the Pathogenesis of Hashimoto Thyroiditis by Reducing Production of Hydrogen Sulfide.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {109}, number = {3}, pages = {792-801}, doi = {10.1210/clinem/dgad588}, pmid = {37793163}, issn = {1945-7197}, mesh = {Animals ; Mice ; Humans ; Female ; *Hashimoto Disease ; *Hydrogen Sulfide ; Mice, Inbred CBA ; *Thyroiditis, Autoimmune ; Feces ; }, abstract = {CONTEXT: Hashimoto thyroiditis (HT) is related to intestinal microbiota alteration, but the causal relationship remains unclear. Hydrogen sulfide (H2S) is a microbiota-derived metabolite. We speculated that abnormal intestinal microbiota might limit H2S production capacity, promoting HT pathogenesis.<br><br>OBJECTIVE: This work aimed to illustrate that the intestinal microbiota plays important roles in HT pathogenesis via microbiota-derived H2S levels.<br><br>METHODS: We collected feces from HT patients and healthy donors for fecal microbiota transplantation (FMT). Thirty-six female CBA/J mice were randomly assigned to 4 groups: experimental autoimmune thyroiditis (EAT) group, EAT + Healthy group, EAT + HT group, and EAT + HT + H2S group. 16S ribosomal RNA sequencing was performed to examine gut microbiota alterations and the H2S production pathway. Serum TgAb and H2S levels were assayed by enzyme-linked immunosorbent assay and H2S-selective sensors, respectively. T-cell subpopulations in the spleen were detected by flow cytometry.<br><br>RESULTS: The gut microbiota was different after FMT among the EAT, EAT + Healthy, and EAT + HT groups. The thyroiditis score assessed by hematoxylin and eosin staining was higher in the EAT + HT group than that in the EAT and EAT + HT + H2S groups. Helper T (Th1) and Th17 cell differentiation ratios were increased in the EAT + HT group compared to the other 3 groups. Serum H2S levels were decreased and the dissimilatory sulfate reduction (DSR) pathway was attenuated in the EAT + HT group compared to the EAT + Healthy group.<br><br>CONCLUSION: H2S alleviated thyroiditis severity and related immune disorders, which were aggravated by the FMT from HT patients. The attenuated DSR pathway in the gut microbiota from HT patients might be involved in thyroiditis pathogenesis.}, }
@article {pmid37791342, year = {2023}, author = {Kamiya, S}, title = {Microbial ecology between Clostridioides difficile and gut microbiota.}, journal = {Bioscience of microbiota, food and health}, volume = {42}, number = {4}, pages = {229-235}, pmid = {37791342}, issn = {2186-6953}, abstract = {Clostridioides difficile colonizes a polymicrobial environment in the intestine and is a causative agent for antibiotic-associated diarrhea (AAD) and pseudomembranous colitis (PMC). The most important virulence factors of C. difficile are bacterial toxins, and three toxins (toxin A, toxin B, and binary toxin) are produced by toxigenic strains. Other virulence factors include spores, flagella, capsules, biofilms, hydrolytic enzymes and adhesins. C. difficile infection (CDI) is specifically diagnosed by anaerobic culture and toxin detection by either nucleic acid amplification test (NAAT) or enzyme-linked immunosorbent assay (ELISA). For treatment of CDI, metronidazole, vancomycin and fidaxomicin are used based on the severity of CDI. Mutual interaction between C. difficile and gut microbiota is associated with pathogenesis of CDI, and decreased microbial diversity with altered gut microbiome was detected in CDI patients. Restoration of certain gut microbiota is considered to be potentially effective for the prevention and treatment of CDI, and an ideal goal for CDI patients is restoration of the gut microbiota to a healthy state. Fecal microbiota transplantation (FMT) is a highly successful method of microbiome restoration and has been reported to be effective for the prevention of recurrent CDI. In addition, approaches to restoring the gut microbiota by using probioitcs and live biotherapeutic products (LBPs) are currently being studied to examine the effect on CDI. Further microbial ecological research on C. difficile and gut microbiota could lead to a better understanding of the pathogenesis and treatment of CDI.}, }
@article {pmid37789073, year = {2023}, author = {Battipaglia, G and Mooyaart, JE and Meyer, R and Mohty, M and Sadowska-Klasa, A and Goloshchapov, O and Locatelli, F and Styczynski, J and Pavlu, J and Dybko, J and Bronin, G and Salmenniemi, U and Jindra, P and Hoogenboom, JD and Kuball, J and Ruggeri, A and Malard, F}, title = {Current use of fecal microbiota transfer in patients with hematologic diseases: a survey on behalf of the Cellular Therapy and Immunobiology Working Party of the EBMT.}, journal = {Bone marrow transplantation}, volume = {58}, number = {12}, pages = {1419-1421}, pmid = {37789073}, issn = {1476-5365}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Hematopoietic Stem Cell Transplantation ; *Hematologic Diseases/therapy ; Surveys and Questionnaires ; }, }
@article {pmid37788279, year = {2023}, author = {Wang, J and Liu, X and Sun, R and Mao, H and Liu, M and Jin, X}, title = {Akkermansia muciniphila participates in the host protection against helminth-induced cardiac fibrosis via TLR2.}, journal = {PLoS pathogens}, volume = {19}, number = {10}, pages = {e1011683}, pmid = {37788279}, issn = {1553-7374}, mesh = {Akkermansia ; *Toll-Like Receptor 2/genetics ; Trichinella spiralis ; *Trichinellosis/immunology ; Humans ; Mice ; RNA, Ribosomal, 16S/genetics ; *Verrucomicrobia/genetics ; Animals ; Fibrosis ; }, abstract = {Helminth Trichinella spiralis (Ts) is one of the major pathogens of human infective myocarditis that can lead to cardiac fibrosis (CF). The gut microbiota involved in this pathology are of interest. Here, we use mice infected with Ts as a model to examine the interactions between gut microbes and host protection to CF. Infected mice show enhanced CF severity. We find that antibiotics treatment to deplete the microbiota aggravates the disease phenotype. Attempts to restore microbiota using fecal microbiota transplantation ameliorates helminth-induced CF. 16S rRNA gene sequencing and metagenomics sequencing reveal a higher abundance of Akkermansia muciniphila in gut microbiomes of Ts-infected mice. Oral supplementation with alive or pasteurized A. muciniphila improves CF via TLR2. This work represents a substantial advance toward our understanding of causative rather than correlative relationships between the gut microbiota and CF.}, }
@article {pmid37787998, year = {2023}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Kazadi, D and Halaweish, H and Khan, MH and Hoeschen, A and Cao, Q and Luo, X and Kabage, AJ and Lopez, S and Holtan, SG and Weisdorf, DJ and Khoruts, A and Staley, C}, title = {Potential of Fecal Microbiota Transplantation to Prevent Acute GVHD: Analysis from a Phase II Trial.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {29}, number = {23}, pages = {4920-4929}, pmid = {37787998}, issn = {1557-3265}, support = {KL2 TR002492/TR/NCATS NIH HHS/United States ; P30 CA077598/CA/NCI NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; Dysbiosis/therapy/complications ; *Gastrointestinal Microbiome ; *Microbiota ; *Graft vs Host Disease/etiology/prevention &amp; control ; Treatment Outcome ; }, abstract = {PURPOSE: Intestinal microbiota disruptions early after allogeneic hematopoietic cell transplantation have been associated with increased risk for acute GVHD (aGVHD). In our recent randomized phase II trial of oral, encapsulated, third-party fecal microbiota transplantation (FMT) versus placebo, FMT at the time of neutrophil recovery was safe and ameliorated dysbiosis. Here, we evaluated in post hoc analysis whether donor microbiota engraftment after FMT may protect against aGVHD.<br><br>EXPERIMENTAL DESIGN: We analyzed pre- and post-FMT stool samples and estimated donor microbiota engraftment (a preplanned secondary endpoint) by determining the fraction of post-FMT microbiota formed by unique donor taxa (donor microbiota fraction; dMf).<br><br>RESULTS: dMf was higher in patients who later developed grade I or no aGVHD (median 33.9%; range, 1.6%-74.3%) than those who developed grade II-IV aGVHD (median 25.3%; range, 2.2%-34.8%; P = 0.006). The cumulative incidence of grade II-IV aGVHD by day 180 was lower in the group with greater-than-median dMf than the group with less-than-median dMf [14.3% (95% confidence interval, CI, 2.1-37.5) vs. 76.9% (95% CI, 39.7-92.8), P = 0.008]. The only determinant of dMf in cross-validated least absolute shrinkage and selection operator (LASSO)-regularized regression was the patient's pre-FMT microbiota diversity (Pearson correlation coefficient -0.82, P = 1.6 &#xd7; 10-9), indicating more potent microbiota modulation by FMT in patients with more severe dysbiosis. Microbiota network analysis revealed major rewiring including changes in the most central nodes, without emergence of keystone species, as a potential mechanism of FMT effect.<br><br>CONCLUSIONS: FMT may have protective effects against aGVHD, especially in patients with more severe microbiota disruptions.}, }
@article {pmid37787835, year = {2024}, author = {Li, S and Zhao, L and Xiao, J and Guo, Y and Fu, R and Zhang, Y and Xu, S}, title = {The gut microbiome: an important role in neurodegenerative diseases and their therapeutic advances.}, journal = {Molecular and cellular biochemistry}, volume = {479}, number = {9}, pages = {2217-2243}, pmid = {37787835}, issn = {1573-4919}, support = {No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 21JCYBJC01620//Tianjin Municipal Science and Technology Commission of China/ ; No. 2021099//Tianjin Health Committee/ ; No. 2021KJ146//Tianjin Education Committee/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Neurodegenerative Diseases/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Animals ; Parkinson Disease/therapy/microbiology ; Alzheimer Disease/therapy/microbiology ; }, abstract = {There are complex interactions between the gut and the brain. With increasing research on the relationship between gut microbiota and brain function, accumulated clinical and preclinical evidence suggests that gut microbiota is intimately involved in the pathogenesis of neurodegenerative diseases (NDs). Increasingly studies are beginning to focus on the association between gut microbiota and central nervous system (CNS) degenerative pathologies to find potential therapies for these refractory diseases. In this review, we summarize the changes in the gut microbiota in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis and contribute to our understanding of the function of the gut microbiota in NDs and its possible involvement in the pathogenesis. We subsequently discuss therapeutic approaches targeting gut microbial abnormalities in these diseases, including antibiotics, diet, probiotics, and fecal microbiota transplantation (FMT). Furthermore, we summarize some completed and ongoing clinical trials of interventions with gut microbes for NDs, which may provide new ideas for studying NDs.}, }
@article {pmid37787395, year = {2023}, author = {Lo Porto, D and Mularoni, A and Castagnola, E and Saffioti, C}, title = {Clostridioides difficile infection in the allogeneic hematopoietic cell transplant recipient.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {25 Suppl 1}, number = {}, pages = {e14159}, doi = {10.1111/tid.14159}, pmid = {37787395}, issn = {1399-3062}, support = {Ricerca Corrente: RC 2022 Linea 1//Italian Ministry of Health/ ; }, mesh = {Adult ; Humans ; Child ; Vancomycin/therapeutic use ; Fidaxomicin/therapeutic use ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Transplant Recipients ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/therapy ; Diarrhea/drug therapy ; }, abstract = {Clostridioides difficile (CD) is one of the most important causes of diarrhea in hospitalized patients, in particular those who undergo an allogeneic hematopoietic cell transplant (allo-HCT) and who are more at risk of developing a CD infection (CDI) due to frequent hospitalizations, iatrogenic immunosuppression, and prolonged antibiotic cycles. CDI may represent a severe condition in allo-HCT patients, increasing the length of hospitalization, influencing the intestinal microbiome with a bidirectional association with graft-versus-host disease, and leading to unfavorable outcomes, including death. The diagnosis of CDI requires the exclusion of other probable causes of diarrhea in HCT patients and is based on highly sensitive and highly specific tests to distinguish colonization from infection. In adult patients, fidaxomicin is recommended as first-line, with oral vancomycin as an alternative agent. Bezlotoxumab may be used to reduce the risk of recurrence. In pediatric patients, vancomycin and metronidazole are still suggested as first-line therapy, but fidaxomicin will probably become standard in pediatrics in the near future. Because of insufficient safety data, fecal microbiota transplantation is not routinely recommended in HCT in spite of promising results for the management of recurrences in other populations.}, }
@article {pmid37787118, year = {2023}, author = {Shou, D and Luo, Q and Tang, W and Cao, C and Huang, H and Chen, H and Zhou, Y}, title = {Hepatobiliary and pancreatic: Multi-donor fecal microbiota transplantation attenuated high-fat diet-induced hepatic steatosis in mice by remodeling the gut microbiota.}, journal = {Journal of gastroenterology and hepatology}, volume = {38}, number = {12}, pages = {2195-2205}, doi = {10.1111/jgh.16359}, pmid = {37787118}, issn = {1440-1746}, support = {81970507//Natural Science Foundation of China/ ; 82170585//Natural Science Foundation of China/ ; 2023A0505010007//Science and Technology Planning Project of Guangdong Province/ ; 2021A1515011290//Natural Science Foundation of Guangdong Province/ ; 2023A03J0955//Guangzhou Municipal Science and Technology Project/ ; }, mesh = {Humans ; Mice ; Animals ; *Non-alcoholic Fatty Liver Disease/etiology/therapy/metabolism ; Diet, High-Fat/adverse effects ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Dysbiosis ; *Noncommunicable Diseases ; Mice, Inbred C57BL ; Liver/metabolism ; }, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) can improve the symptoms of nonalcoholic fatty liver disease (NAFLD) by restoring the gut microbiota. This study was aimed to evaluate the therapeutic effects of single-donor (SD) or multi-donor (MD) FMT in a mouse model of hepatic steatosis and explore the underlying mechanisms.<br><br>METHODS: Fecal samples were collected from NAFLD patients and healthy controls with similar baseline characteristics, with gut microbiota analyzed. Mice were fed either a normal-chow diet (NCD) or a high-fat diet (HFD) for 3&#xa0;weeks and then administered fecal microbiota collected from healthy SDs or MDs for 12&#xa0;weeks.<br><br>RESULTS: Fecal samples from NAFLD patients showed significantly lower microbial diversity than those from healthy controls. MD-FMT reduced liver fat accumulation and body weight and significantly improved serum and liver biochemical indices in HFD-fed mice. Compared to untreated HFD-fed mice, MD-FMT significantly decreased the relative expression of IL-1&#x3b2;, IL-6, TNF-&#x3b1;, IFN-&#x3b3;, and IL-1&#x3b2; mRNAs in the liver. The relative protein level of intestinal barrier components, including claudin-1, occludin, and E-cadherin, as well as serum lipopolysaccharide (LPS) level in mice, were found to be improved following MD-FMT intervention. Furthermore, FMT reversed HFD-induced gut dysbiosis and increased the abundance of beneficial bacteria such as Blautia and Akkermansia.<br><br>CONCLUSION: NAFLD patients and healthy controls showed distinct gut microbiota. Likewise, HFD altered gut microbiota in mice compared to NCD-fed controls. MD-FMT restored gut dysbiosis in HFD-fed mice and attenuated liver steatosis, and should be considered as an effective treatment option for NAFLD.}, }
@article {pmid37781523, year = {2023}, author = {Shao, X and Liu, L and Zhou, Y and Zhong, K and Gu, J and Hu, T and Yao, Y and Zhou, C and Chen, W}, title = {High-fat diet promotes colitis-associated tumorigenesis by altering gut microbial butyrate metabolism.}, journal = {International journal of biological sciences}, volume = {19}, number = {15}, pages = {5004-5019}, pmid = {37781523}, issn = {1449-2288}, mesh = {Mice ; Animals ; Butyrates/therapeutic use ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Obesity/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; *Colitis ; Inflammation ; Cell Transformation, Neoplastic ; Carcinogenesis ; Caspases ; }, abstract = {Background: Dietary fat intake is associated with an increased risk of colitis associated cancer (CAC). A high-fat diet (HFD) leads to systemic low-grade inflammation. The colon is believed to be the first organ suffering from inflammation caused by the infiltration of pro-inflammatory macrophages, and promotes CAC progression. We explored the role of HFD in driving CAC by altering gut microbial butyrate metabolism. Methods: Changes in the gut microbiota caused by HFD were investigated via HFD treatment or fecal microbiota transplantation (FMT). The underlying mechanisms were further explored by analyzing the role of gut microbiota, microbial butyrate metabolism, and NLRP3 inflammasome in colon tissues in a CAC mouse model. Results: HFD accelerated CAC progression in mice, and it could be reversed by broad-spectrum antibiotics (ABX). 16S-rRNA sequencing revealed that HFD inhibited the abundance of butyrate-producing bacteria in the gut. The level of short-chain fatty acids (SCFAs), especially butyrate, in the gut of mice treated with HFD was significantly reduced. In addition, treatment with exogenous butyrate reversed the M1 polarization of proinflammatory macrophages, aggravation of intestinal inflammation, and accelerated tumor growth induced by HFD; the NLRP3/Caspase-1 pathway activated by HFD in the colon was also significantly inhibited. In vitro, macrophages were treated with lipopolysaccharide combined with butyrate to detect the M1 polarization level and NLRP3/Caspase-1 pathway expression, and the results were consistent with those of the in vivo experiments. Conclusion: HFD drives colitis-associated tumorigenesis by inducing gut microbial dysbiosis and inhibiting butyrate metabolism to skew macrophage polarization. Exogenous butyrate is a feasible new treatment strategy for CAC, and has good prospect for clinical application.}, }
@article {pmid37781044, year = {2023}, author = {Zhang, L and Ji, Q and Chen, Q and Wei, Z and Liu, S and Zhang, L and Zhang, Y and Li, Z and Liu, H and Sui, H}, title = {Akkermansia muciniphila inhibits tryptophan metabolism via the AhR/β-catenin signaling pathway to counter the progression of colorectal cancer.}, journal = {International journal of biological sciences}, volume = {19}, number = {14}, pages = {4393-4410}, pmid = {37781044}, issn = {1449-2288}, mesh = {Sequence Analysis, DNA ; Phylogeny ; RNA, Ribosomal, 16S ; Receptors, Aryl Hydrocarbon/genetics/metabolism ; Base Composition ; Wnt Signaling Pathway ; Humans ; *Colonic Neoplasms ; Animals ; Mice, Inbred C57BL ; Akkermansia ; beta Catenin/metabolism ; Tryptophan/adverse effects ; Mice ; *Colorectal Neoplasms/metabolism ; }, abstract = {Akkermansia muciniphila (A. muciniphila), a gram-negative anaerobic bacterium, is selectively decreased in the fecal microbiota of patients with colorectal cancer (CRC), but its molecular mechanism in CRC development remains inconclusive. In this study, we first confirmed the inhibitory effect of A. muciniphila on CRC formation and analyzed the metabolic role of intestinal flora in human Polyps, A-CRA (advanced colorectal adenoma) and CRC samples. To better clarify the role of A. muciniphila in CRC development, a pseudo-germ-free (GF) azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model was established, followed by infection with or without A. muciniphila. Metabolomic analysis and RNA-seq analysis showed tryptophan-mediated aryl hydrocarbon receptor (AhR) was significantly down-regulated in A. muciniphila-infected CRC mice. Then, mice with intestinal specific AhR deficiency (AhR[fl/fl] Cre) were generated and were used in 2 murine models: AOM/DSS treatment as a model of carcinogen-induced colon cancer and a genetically induced model using Apc[Min/+] mice. Notably, AhR deficiency inhibited CRC growth in the AOM/DSS and Apc[Min/+] mouse model. Moreover, AhR deficiency inhibited, rather than enhanced, tumor formation and tumor-derived organoids in Apc-deficient cells both in vivo and in vitro by activating Wnt/β-catenin signaling and TCF4/LEF1-dependent transcription. Furthermore, the antitumor effectiveness of A. muciniphila was abolished either in a human colon cancer tumor model induced by subcutaneous transplantation of AhR-silenced CRC cells, or AhR-deficienty spontaneous colorectal cancer model. In conclusion, supplementation with A. muciniphila. protected mice from CRC development by specifically inhibiting tryptophan-mediated AhR/β-catenin signaling.}, }
@article {pmid37780282, year = {2023}, author = {Li, W and Zhang, W and Fan, X and Xu, H and Yuan, H and Wang, Y and Yang, R and Tian, H and Wu, Y and Yang, H}, title = {Fructo-oligosaccharide enhanced bioavailability of polyglycosylated anthocyanins from red radish via regulating gut microbiota in mice.}, journal = {Food chemistry: X}, volume = {19}, number = {}, pages = {100765}, pmid = {37780282}, issn = {2590-1575}, abstract = {The anthocyanins from red radish (ARR) rich in polyglycosylated pelargonidin glucosides were used as pigment. However, bioavailability of anthocyanins was considered at low level. This work examined the intensive effects of fructo-oligosaccharide (FOS) on ARR bioavailability. Pelargonidin, cyanidin and pelargonidin-3-glucoside showed higher level in serum of mice fed with FOS together with ARR for 8 weeks than that fed with only ARR. Co-ingestion of FOS and ARR more effectively elevated the hepatic antioxidant activity by increase in total antioxidant capacity and activities of superoxide dismutase and glutathione peroxidase when compared with intake of ARR. FOS also markedly increased pelargonidin level in cecum of mice. 16S RNA sequencing found that Bacteroides genus play an important role in FOS elevating bioavailability of ARR. Fecal bacteria transplantation verified the positive effects of FOS on ARR bioavailability. These results suggested that combined ingestion of FOS and ARR is effective strategy for bioactivity of ARR.}, }
@article {pmid37779873, year = {2023}, author = {Machado, AP and Shatila, M and De Toni, EN and Török, HP and Philpott, J and Zhao, D and Zhou, Y and Varatharajalu, K and Shafi, MA and Zhang, HC and Thomas, AS and Wang, Y}, title = {Colon Adenoma After Diagnosis of Immune Checkpoint Inhibitor-mediated Colitis.}, journal = {Journal of Cancer}, volume = {14}, number = {14}, pages = {2686-2693}, pmid = {37779873}, issn = {1837-9664}, abstract = {Purpose: While the occurrence of colitis during immune checkpoint inhibitor (ICI) treatment is recognized as a sign of robust immune activation and correlates with better oncological outcomes, the long-term impact of ICI-mediated colitis on the colonic mucosa has not been studied. We thus aim to describe the colonoscopy and histology findings in patients at a follow-up time of ≥ 6 months post initial colitis event. Methods: This retrospective analysis included adult cancer patients diagnosed with ICI colitis at a tertiary cancer center between October 2013 and June 2020. The study group included patients diagnosed with immune mediated colitis who had also undergone a follow up colonoscopy or flex sigmoidoscopy. The control group was patients exposed to ICI without immune mediated colitis. We reported patients' colitis clinical course, treatment, outcomes, and endoscopic and histologic features at diagnosis and at follow-up time of ≥ 6 months. Results: Total 39 patients met the study criteria, with 82% being male, and 35.8% having melanoma. Most patients received a combination of CTLA-4 and PD-1/L1 inhibitors (82%). On initial endoscopic evaluation, inflammation without ulceration was reported in 76.9% of patients and active inflammation on histologic examination in 79.3% of patients. Most patients (79.4%) received corticosteroids, and 56.4% received add-on selective immunosuppressive therapy. Four patients received fecal microbiota transplantation. On follow-up, new incidence of colonic polyps was reported in 51.2% of patients, including adenomas in 33.3% among the colitis patients with median follow up duration of 12 months. The incidence of adenoma polyps 12 months after the colitis event was significantly higher compared to the control group without colitis based on the time-to-event analysis (p=0.041). Conclusion: At a median follow up of 12 months after their initial colitis diagnosis, 51.2% of the patients had new incidence of colonic polyps, including a third with adenoma, at a significantly higher incidence than the control group without colitis. Studies with larger sample sizes are needed to further define the long-term impact of colitis and its treatments on colon health and to refine recommendations for surveillance of colonic adenomas and colorectal cancer.}, }
@article {pmid37778924, year = {2024}, author = {Custer, GF and Bresciani, L and Dini-Andreote, F}, title = {Toward an integrative framework for microbial community coalescence.}, journal = {Trends in microbiology}, volume = {32}, number = {3}, pages = {241-251}, doi = {10.1016/j.tim.2023.09.001}, pmid = {37778924}, issn = {1878-4380}, mesh = {*Microbiota ; }, abstract = {Community coalescence is defined as the mixing of intact ecological communities. From river confluences to fecal microbiota transplantation, community coalescence constitutes a common ecological occurrence affecting natural and engineered microbial systems. In this opinion article, we propose an integrative framework for microbial community coalescence to guide advances in our understanding of this important - yet underexplored - ecological phenomenon. We start by aligning community coalescence with the unified framework of biological invasion and enumerate commonalities and idiosyncrasies between these two analogous processes. Then, we discuss how organismal interactions and cohesive establishment affect coalescence outcomes with direct implications for community functioning. Last, we propose the use of ecological null modeling to study the interplay of ecological processes structuring community reassembly following coalescence.}, }
@article {pmid37777765, year = {2023}, author = {Wen, Y and Yang, L and Wang, Z and Liu, X and Gao, M and Zhang, Y and Wang, J and He, P}, title = {Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig model.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {218}, pmid = {37777765}, issn = {2049-2618}, mesh = {Mice ; Animals ; Swine ; Butyrates/metabolism ; *Lactobacillus johnsonii/metabolism ; Copper ; Acetates ; *Microbiota ; }, abstract = {BACKGROUND: High-copper diets have been widely used to promote growth performance of pigs, but excess copper supplementation can also produce negative effects on ecosystem stability and organism health. High-copper supplementation can damage the intestinal barrier and disturb the gut microbiome community. However, the specific relationship between high-copper-induced intestinal damage and gut microbiota or its metabolites is unclear.<br><br>OBJECTIVE: Using fecal microbiota transplantation and metagenomic sequencing, responses of colonic microbiota to a high-copper diet was profiled. In addition, via comparison of specific bacteria and its metabolites rescue, we investigated a network of bacteria-metabolite interactions involving conversion of specific metabolites as a key mechanism linked to copper-induced damage of the colon.<br><br>RESULTS: High copper induced colonic damage, Lactobacillus extinction, and reduction of SCFA (acetate and butyrate) concentrations in pigs. LefSe analysis and q-PCR results confirmed the extinction of L. johnsonii. In addition, transplanting copper-rich fecal microbiota to ABX mice reproduced the gut characteristics of the pig donors. Then, L. johnsonii rescue could restore decreased SCFAs (mainly acetate and butyrate) and colonic barrier damage including thinner mucus layer, reduced colon length, and tight junction protein dysfunction. Given that acetate and butyrate concentrations exhibited a positive correlation with L. johnsonii abundance, we investigated how L. johnsonii exerted its effects by supplementing acetate and butyrate. L. johnsonii and butyrate administration but not acetate could correct the damaged colonic barrier. Acetate administration had no effects on butyrate concentration, indicating blocked conversion from acetate to butyrate. Furthermore, L. johnsonii rescue enriched a series of genera with butyrate-producing ability, mainly Lachnospiraceae NK4A136 group.<br><br>CONCLUSIONS: For the first time, we reveal the microbiota-mediated mechanism of high-copper-induced colonic damage in piglets. A high-copper diet can induce extinction of L. johnsonii which leads to colonic barrier damage and loss of SCFA production. Re-establishment of L. johnsonii normalizes the SCFA-producing pathway and restores colonic barrier function. Mechanistically, Lachnospiraceae NK4A136 group mediated conversion of acetate produced by L. johnsonii to butyrate is indispensable in the protection of colonic barrier function. Collectively, these findings provide a feasible mitigation strategy for gut damage caused by high-copper diets. Video Abstract.}, }
@article {pmid37775582, year = {2024}, author = {Samaey, A and Vázquez-Castellanos, JF and Caenepeel, C and Evenepoel, P and Vermeire, S and Raes, J and Knops, N}, title = {Effects of fecal microbiota transplantation for recurrent Clostridium difficile infection in children on kidney replacement therapy: a pilot study.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {39}, number = {4}, pages = {1201-1212}, pmid = {37775582}, issn = {1432-198X}, support = {1236321N//FWO Vlaanderen/ ; }, mesh = {Child ; Humans ; Child, Preschool ; Fecal Microbiota Transplantation/methods ; Pilot Projects ; Dysbiosis/therapy ; *Clostridium Infections/therapy/microbiology ; Treatment Outcome ; Renal Replacement Therapy ; Leukocyte L1 Antigen Complex ; *Renal Insufficiency, Chronic/therapy ; Recurrence ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (rCDI) is a rising problem in children with chronic diseases. Fecal microbiota transplantation (FMT) is a recent alternative for rCDI patients who do not respond to conventional treatment. FMT could have an additional positive effect on the intestinal dysbiosis and accumulation of uremic retention molecules (URM) associated with chronic kidney disease (CKD). Our aim was to investigate the clinical efficacy of FMT for rCDI in children with CKD together with the effect on dysbiosis and URM levels.<br><br>METHODS: We analyzed stool and blood samples before and until 3&#xa0;months after FMT in 3 children between 4 and 8&#xa0;years old with CKD and rCDI. The microbiome was analyzed by 16&#xa0;s rRNA sequencing. URM were analyzed with ultra-performance liquid chromatography-tandem mass spectrometry. CRP and fecal calprotectin were analyzed as parameters for systemic and gut inflammation, respectively.<br><br>RESULTS: CDI resolved after FMT in all three without adverse events; one patient needed a second FMT. No significant effect on CRP and calprotectin was observed. Stool samples demonstrated a reduced richness and bacterial diversity which did not improve after FMT. We did observe a trend in the decrease of specific URM up to 3&#xa0;months after FMT.<br><br>CONCLUSION: FMT is an effective treatment for rCDI in patients with CKD. Analysis of the microbiome showed an important intestinal dysbiosis that, besides a significant reduction in Clostridium difficile, did not significantly change after FMT. A trend for reduction was seen in some of the measured URM after FMT.}, }
@article {pmid37774733, year = {2023}, author = {Mandal, S and Simmons, R and Ireland, G and Charlett, A and Desai, M and Coughlan, L and Powell, A and Leeman, D and Williams, C and Neill, C and O'Leary, MC and Sawyer, C and Rowley, F and Harris, C and Houlihan, C and Gordon, C and Rampling, T and Callaby, H and Hoschler, K and Cogdale, J and Renz, E and Sebastianpilli, P and Thompson, C and Talts, T and Celma, C and Davies, EA and Ahmad, S and Machin, N and Gifford, L and Moore, C and Dickson, EM and Divala, TH and Henderson, D and Li, K and Broadbent, P and Ushiro-Lumb, I and Humphreys, C and Grammatikopoulos, T and Hartley, J and Kelgeri, C and Rajwal, S and Okike, I and Kelly, DA and Guiver, M and Borrow, R and Bindra, R and Demirjian, A and Brown, KE and Ladhani, SN and Ramsay, ME and Bradley, DT and Gjini, A and Roy, K and Chand, M and Zambon, M and Watson, CH}, title = {Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.}, journal = {The Lancet. Child &amp; adolescent health}, volume = {7}, number = {11}, pages = {786-796}, doi = {10.1016/S2352-4642(23)00215-8}, pmid = {37774733}, issn = {2352-4650}, mesh = {Child, Preschool ; Female ; Humans ; Male ; Acute Disease ; Case-Control Studies ; *COVID-19 ; *Hepatitis ; SARS-CoV-2 ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes.<br><br>METHODS: We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information. Then, we did a case-control study to investigate the association between adenoviraemia and other viruses and case-status using multivariable Firth penalised logistic regression. Cases aged 1-10 years and tested for adenovirus were included and compared with controls (ie, children admitted to hospital with an acute non-hepatitis illness who had residual blood samples collected between Jan 1 and May 28, 2022, and without known laboratory-confirmed diagnosis or previous adenovirus testing). Controls were frequency-matched on sex, age band, sample months, and nation or supra-region with randomised selection. We explored temporal associations between frequency of circulating viruses identified through routine laboratory pathogen surveillance and occurrence of cases by linear regression. SARS-CoV-2 seropositivity of cases was examined against residual serum from age-matched clinical comparison groups.<br><br>FINDINGS: Between Jan 1 and July 4, 2022, 274 cases were identified (median age 3 years [IQR 2-5]). 131 (48%) participants were male, 142 (52%) were female, and one (<1%) participant had sex data unknown. Jaundice (195 [83%] of 235) and gastrointestinal symptoms (202 [91%] of 222) were common. 15 (5%) children required liver transplantation and none died. Adenovirus was detected in 172 (68%) of 252 participants tested, regardless of sample type; 137 (63%) of 218 samples were positive for adenovirus in the blood. For cases that were successfully genotyped, 58 (81%) of 72 had Ad41F, and 57 were identified as positive via blood samples (six of these were among participants who had undergone a transplant). In the case-control analysis, adenoviraemia was associated with hepatitis case-status (adjusted OR 37&#xb7;4 [95% CI 15&#xb7;5-90&#xb7;3]). Increases in the detection of adenovirus from faecal samples, but not other infectious agents, in routine laboratory pathogen surveillance correlated with hepatitis cases 4 weeks later, which independently suggested an association (&#x3b2; 0&#xb7;06 [95% CI 0&#xb7;02-0&#xb7;11]). No association was identified for SARS-CoV-2 antibody seropositivity.<br><br>INTERPRETATION: We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation.<br><br>FUNDING: None.}, }
@article {pmid37771706, year = {2023}, author = {Feng, E and Yang, X and Zhao, K and Li, Y and Zhu, H and Wang, Z and Zhang, Z}, title = {Gut microbiota is associated with spatial memory and seed-hoarding behavior of South China field mice (Apodemus draco).}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1236359}, pmid = {37771706}, issn = {1664-302X}, abstract = {BACKGROUND: Scatter-hoarding animals store food in multiple locations within their home range and rely on spatial memory for subsequent localization and retrieval. The relationship between memory and scatter-hoarding behavior has been widely demonstrated, but the association of gut microbiota with spatial memory and seed-hoarding behavior of animals remains unclear.<br><br>METHODS: In this study, by using enclosure behavior tests, memory tests including an object location test (OLT) and a novel object recognition test (NORT), and fecal microbiota transplantation (FMT) experiment, we evaluated the role of gut microbiota in affecting the memory and seed-hoarding behavior of rodents. According to their scatter-hoarding intensity, South China field mice (Apodemus draco) were divided into scatter-hoarding group (SG) and non-scatter-hoarding group (NG).<br><br>RESULTS: We found that the SG performed better than the NG in the NORT. FMT from SG donor mice altered the NG recipient mice's gut microbiota structure. Further tests demonstrated FMT from SG donor mice increased memory of NG recipient mice in laboratory tests and seed larder hoarding intensity of NG recipient mice in enclosures.<br><br>CONCLUSION: Our results suggest gut microbiota could modulate the memory and seed-hoarding behavior of animals.}, }
@article {pmid37771694, year = {2023}, author = {Tang, J and Zhang, H and Yin, L and Zhou, Q and Zhang, H}, title = {The gut microbiota from maintenance hemodialysis patients with sarcopenia influences muscle function in mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1225991}, pmid = {37771694}, issn = {2235-2988}, mesh = {Humans ; Mice ; Animals ; *Sarcopenia/etiology ; *Gastrointestinal Microbiome/physiology ; RNA, Ribosomal, 16S/genetics ; Fecal Microbiota Transplantation ; *Muscular Diseases ; Muscles ; }, abstract = {BACKGROUND: Sarcopenia is a common complication in patients undergoing maintenance hemodialysis (MHD). Growing evidence suggests a close relationship between the gut microbiota and skeletal muscle. However, research on gut microbiota in patients with sarcopenia undergoing MHD (MS) remains scarce. To bridge this knowledge gap, we aimed to evaluate the pathogenic influence of gut microbiota in the skeletal muscle of patients with MS, to clarify the causal association between gut microbiota and skeletal muscle symptoms in patients with MS and identify the potential mechanisms underlying this causal association.<br><br>METHODS: Fecal samples were collected from 10 patients with MS and 10 patients without MS (MNS). Bacteria were extracted from these samples for transplantation. Mice (n=42) were randomly divided into three groups and, after antibiotic treatment, fecal microbiota transplantation (FMT) was performed once a day for 3 weeks. Skeletal muscle and fecal samples from the mice were collected for 16S rRNA gene sequencing and for histological, real-time PCR, and metabolomic analyses.<br><br>RESULTS: Mice colonized with gut microbiota from MS patients exhibited notable decreases in muscle function and muscle mass, compared with FMT from patients with MNS. Moreover, 16S rRNA sequencing revealed that the colonization of MS gut microbiota reduced the abundance of Akkermansia in the mouse intestines. Metabolome analysis revealed that seven metabolic pathways were notably disrupted in mice transplanted with MS microbiota.<br><br>CONCLUSION: This study established a connection between skeletal muscle and the gut microbiota of patients with MS, implying that disruption of the gut microbiota may be a driving factor in the development of skeletal muscle disorders in patients undergoing MHD. This finding lays the foundation for understanding the pathogenesis and potential treatment methods for sarcopenia in patients undergoing MHD.}, }
@article {pmid37771199, year = {2024}, author = {Horvath, A and Zukauskaite, K and Hazia, O and Balazs, I and Stadlbauer, V}, title = {Human gut microbiome: Therapeutic opportunities for metabolic syndrome-Hype or hope?.}, journal = {Endocrinology, diabetes &amp; metabolism}, volume = {7}, number = {1}, pages = {e436}, pmid = {37771199}, issn = {2398-9238}, support = {KLI 741/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Metabolic Syndrome/therapy ; Prebiotics ; *Microbiota ; *Metabolic Diseases/therapy/etiology ; }, abstract = {Shifts in gut microbiome composition and metabolic disorders are associated with one another. Clinical studies and experimental data suggest a causal relationship, making the gut microbiome an attractive therapeutic goal. Diet, intake of probiotics or prebiotics and faecal microbiome transplantation (FMT) are methods to alter a person's microbiome composition. Although FMT may allow establishing a proof of concept to use microbiome modulation to treat metabolic disorders, studies show mixed results regarding the effects on metabolic parameters as well as on the composition of the microbiome. This review summarizes the current knowledge on diet, probiotics, prebiotics and FMT to treat metabolic diseases, focusing on studies that also report alterations in microbiome composition. Furthermore, clinical trial results on the effects of common drugs used to treat metabolic diseases are synopsized to highlight the bidirectional relationship between the microbiome and metabolic diseases. In conclusion, there is clear evidence that microbiome modulation has the potential to influence metabolic diseases; however, it is not possible to distinguish which intervention is the most successful. In addition, a clear commitment from all stakeholders is necessary to move forward in the direction of developing targeted interventions for microbiome modulation.}, }
@article {pmid37770953, year = {2023}, author = {Zhang, M and Liu, J and Xia, Q}, title = {Role of gut microbiome in cancer immunotherapy: from predictive biomarker to therapeutic target.}, journal = {Experimental hematology &amp; oncology}, volume = {12}, number = {1}, pages = {84}, pmid = {37770953}, issn = {2162-3619}, support = {2022ZZ01016//Shanghai Organ Transplantation Research Center/ ; 92059205//National Natural Science Foundation of China/ ; }, abstract = {Immunotherapy has emerged as an effective treatment for various types of cancers. Recent studies have highlighted a significant correlation between the gut microbiome and patients' response to immunotherapy. Several characteristics of the gut microbiome, such as community structures, taxonomic compositions, and molecular functions, have been identified as crucial biomarkers for predicting immunotherapy response and immune-related adverse events (irAEs). Unlike other -omics, the gut microbiome can serve as not only biomarkers but also potential targets for enhancing the efficacy of immunotherapy. Approaches for modulating the gut microbiome include probiotics/prebiotics supplementation, dietary interventions, fecal microbiota transplantation (FMT), and antibiotic administration. This review primarily focuses on elucidating the potential role of the gut microbiome in predicting the response to cancer immunotherapy and improving its efficacy. Notably, we explore reasons behind inconsistent findings observed in different studies, and highlight the underlying benefits of antibiotics in liver cancer immunotherapy.}, }
@article {pmid37769622, year = {2023}, author = {Rossier, L and Matter, C and Burri, E and Galperine, T and Hrúz, P and Juillerat, P and Schoepfer, A and Vavricka, SR and Zahnd, N and Décosterd, N and Seibold, F}, title = {Swiss expert opinion: current approaches in faecal microbiota transplantation in daily practice.}, journal = {Swiss medical weekly}, volume = {153}, number = {}, pages = {40100}, doi = {10.57187/smw.2023.40100}, pmid = {37769622}, issn = {1424-3997}, mesh = {Humans ; *Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; *Colitis, Ulcerative/etiology/therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Inflammatory Bowel Diseases/therapy ; Switzerland ; Treatment Outcome ; }, abstract = {INTRODUCTION: Faecal microbiota transplantation (FMT) is an established therapy for recurrent C. difficile infection, and recent studies have reported encouraging results of FMT in patients with ulcerative colitis. Few international consensus guidelines exist for this therapy, and thus FMT policies and practices differ among European countries. As of 2019, stool transplants are considered a non-standardised medicinal product in Switzerland, and a standardised production process requires authorisation by the Swiss Agency for Therapeutic Products. This authorisation leads to prolonged administrative procedures and increasing costs, which reduces treatment accessibility. In particular, patients with ulcerative colitis in Switzerland can only benefit from FMT off-label, even though it is a valid therapeutic option. Therefore, this study summarised the available data on FMT and established a framework for the standardised use of FMT.<br><br>METHODS: A panel of Swiss gastroenterologists with a special interest in inflammatory bowel disease was established to identify the current key issues of FMT. After a comprehensive review of the literature, statements were formulated about FMT indications, donor screening, stool transplant preparation and administration, and safety aspects. The panel then voted on the statements following the Delphi process; the statements were reformulated and revoted until a consensus was reached. The manuscript was then reviewed by an infectiologist (the head of Lausanne's FMT centre).<br><br>RESULTS: The established statements are summarised in the supplementary tables in the appendix to this paper. The working group hopes these will help standardise FMT practice in Switzerland and contribute to making faecal microbiota transplantation a safe and accessible treatment for patients with recurrent&#xa0;C. difficile&#xa0;infections and selected patients with ulcerative colitis, as well as other indications in the future.}, }
@article {pmid37764957, year = {2023}, author = {Boicean, A and Bratu, D and Fleaca, SR and Vasile, G and Shelly, L and Birsan, S and Bacila, C and Hasegan, A}, title = {Exploring the Potential of Fecal Microbiota Transplantation as a Therapy in Tuberculosis and Inflammatory Bowel Disease.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {9}, pages = {}, pmid = {37764957}, issn = {2076-0817}, support = {contract no. 28PFE/30.12.2021//Ministerul Cercet&#x103;rii &#x219;i Inov&#x103;rii/ ; }, abstract = {This review explores the potential benefits of fecal microbiota transplantation (FMT) as an adjunct treatment in tuberculosis (TB), drawing parallels from its efficacy in inflammatory bowel disease (IBD). FMT has shown promise in restoring the gut microbial balance and modulating immune responses in IBD patients. Considering the similarities in immunomodulation and dysbiosis between IBD and TB, this review hypothesizes that FMT may offer therapeutic benefits as an adjunct therapy in TB. Methods: We conducted a systematic review of the existing literature on FMT in IBD and TB, highlighting the mechanisms and potential implications of FMT in the therapeutic management of both conditions. The findings contribute to understanding FMT's potential role in TB treatment and underscore the necessity for future research in this direction to fully leverage its clinical applications. Conclusion: The integration of FMT into the comprehensive management of TB could potentially enhance treatment outcomes, reduce drug resistance, and mitigate the side effects of conventional therapies. Future research endeavors should focus on well-designed clinical trials to develop guidelines concerning the safety and short- and long-term benefits of FMT in TB patients, as well as to assess potential risks.}, }
@article {pmid37764783, year = {2023}, author = {Li, L and Wu, L and Jiang, T and Liang, T and Yang, L and Li, Y and Gao, H and Zhang, J and Xie, X and Wu, Q}, title = {Lactiplantibacillus plantarum 124 Modulates Sleep Deprivation-Associated Markers of Intestinal Barrier Dysfunction in Mice in Conjunction with the Regulation of Gut Microbiota.}, journal = {Nutrients}, volume = {15}, number = {18}, pages = {}, pmid = {37764783}, issn = {2072-6643}, support = {(2022B1111070006)//the Key Research and Development Program of Guangdong Province/ ; 2019QN01N107//the Department of Science and Technology of Guangdong Province/ ; 2020GDASYL-20200102003//GDAS' Project of Science and Technology Development/ ; }, mesh = {Animals ; Mice ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome ; Sleep Deprivation ; *Gastrointestinal Diseases ; *Intestinal Diseases ; Firmicutes ; Cytokines ; }, abstract = {Intestinal diseases caused by sleep deprivation (SD) are severe public health threats worldwide. However, whether or not probiotics attenuate the intestinal damage associated with SD remains unclear. In this study, we used antibiotic pretreatment and fecal microbiota transplantation to investigate the protective role of Lactiplantibacillus plantarum (L. plantarum) 124 against SD-related intestinal barrier damage in C57BL/6 mice. Compared with those of a normal sleeping mouse, we observed that intestinal antioxidant capacity and anti-inflammatory cytokine levels were decreased, while pro-inflammatory cytokines were increased in sleep deprivation mice with an increasing duration of sleep deprivation. This resulted in decreased tight junction protein expression and increased intestinal barrier permeability. In contrast, intragastric administration with L. plantarum 124 reversed SD-associated intestinal oxidative stress, inflammation, colonic barrier damage, and the dysbiosis of the microbiota in the colon. In addition, L. plantarum 124 restored gut microbiota homeostasis via restoring abundance, including that of Dubosiella, Faecalibaculum, Bacillus, Lachnoclostridium, and Bifidobacterium. Further studies showed that gut microbiota mediated SD-associated intestinal damage and the treatment L. plantarum 124 in SD-associated colonic barrier damage. L. plantarum 124 is a potential candidate for alleviating SD-associated intestinal barrier damage. Overall, L. plantarum 124 consumption attenuates intestinal oxidative stress, inflammation, and intestinal barrier damage in SD-associated mice via the modulation of gut microbes.}, }
@article {pmid37764082, year = {2023}, author = {Bénard, MV and Arretxe, I and Wortelboer, K and Harmsen, HJM and Davids, M and de Bruijn, CMA and Benninga, MA and Hugenholtz, F and Herrema, H and Ponsioen, CY}, title = {Anaerobic Feces Processing for Fecal Microbiota Transplantation Improves Viability of Obligate Anaerobes.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, pmid = {37764082}, issn = {2076-2607}, support = {innovation grant 2021 - Amsterdam Gastroenterology Endocrinology Metabolism (AGEM)//University of Amsterdam/ ; }, abstract = {Fecal microbiota transplantation (FMT) is under investigation for several indications, including ulcerative colitis (UC). The clinical success of FMT depends partly on the engraftment of viable bacteria. Because the vast majority of human gut microbiota consists of anaerobes, the currently used aerobic processing protocols of donor stool may diminish the bacterial viability of transplanted material. This study assessed the effect of four processing techniques for donor stool (i.e., anaerobic and aerobic, both direct processing and after temporary cool storage) on bacterial viability. By combining anaerobic culturing on customized media for anaerobes with 16S rRNA sequencing, we could successfully culture and identify the majority of the bacteria present in raw fecal suspensions. We show that direct anaerobic processing of donor stool is superior to aerobic processing conditions for preserving the bacterial viability of obligate anaerobes and butyrate-producing bacteria related to the clinical response to FMT in ulcerative colitis patients, including Faecalibacterium, Eubacterium hallii, and Blautia. The effect of oxygen exposure during stool processing decreased when the samples were stored long-term. Our results confirm the importance of sample conditioning to preserve the bacterial viability of oxygen-sensitive gut bacteria. Anaerobic processing of donor stool may lead to increased clinical success of FMT, which should further be investigated in clinical trials.}, }
@article {pmid37764025, year = {2023}, author = {Metafuni, E and Di Marino, L and Giammarco, S and Bellesi, S and Limongiello, MA and Sorà, F and Frioni, F and Maggi, R and Chiusolo, P and Sica, S}, title = {The Role of Fecal Microbiota Transplantation in the Allogeneic Stem Cell Transplant Setting.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, pmid = {37764025}, issn = {2076-2607}, abstract = {Microbiota changes during allogeneic hematopoietic stem cell transplantation has several known causes: conditioning chemotherapy and radiation, broad-spectrum antibiotic administration, modification in nutrition status and diet, and graft-versus-host disease. This article aims to review the current knowledge about the close link between microbiota and allogeneic stem cell transplantation setting. The PubMed search engine was used to perform this review. We analyzed data on microbiota dysbiosis related to the above-mentioned affecting factors. We also looked at treatments aimed at modifying gut dysbiosis and applications of fecal microbiota transplantation in the allogeneic stem cell transplant field, with particular interest in fecal microbiota transplantation for graft-versus-host disease (GvHD), multidrug-resistant and clostridium difficile infections, and microbiota restoration after chemotherapy and antibiotic therapy.}, }
@article {pmid37764005, year = {2023}, author = {Dicks, LMT}, title = {Biofilm Formation of Clostridioides difficile, Toxin Production and Alternatives to Conventional Antibiotics in the Treatment of CDI.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, pmid = {37764005}, issn = {2076-2607}, abstract = {Clostridioides difficile is considered a nosocomial pathogen that flares up in patients exposed to antibiotic treatment. However, four out of ten patients diagnosed with C. difficile infection (CDI) acquired the infection from non-hospitalized individuals, many of whom have not been treated with antibiotics. Treatment of recurrent CDI (rCDI) with antibiotics, especially vancomycin (VAN) and metronidazole (MNZ), increases the risk of experiencing a relapse by as much as 70%. Fidaxomicin, on the other hand, proved more effective than VAN and MNZ by preventing the initial transcription of RNA toxin genes. Alternative forms of treatment include quorum quenching (QQ) that blocks toxin synthesis, binding of small anion molecules such as tolevamer to toxins, monoclonal antibodies, such as bezlotoxumab and actoxumab, bacteriophage therapy, probiotics, and fecal microbial transplants (FMTs). This review summarizes factors that affect the colonization of C. difficile and the pathogenicity of toxins TcdA and TcdB. The different approaches experimented with in the destruction of C. difficile and treatment of CDI are evaluated.}, }
@article {pmid37762509, year = {2023}, author = {Zabolotneva, AA and Gaponov, AM and Roumiantsev, SA and Vasiliev, IY and Grigoryeva, TV and Kit, OI and Zlatnik, EY and Maksimov, AY and Goncharova, AS and Novikova, IA and Appolonova, SA and Markin, PA and Shestopalov, AV}, title = {Alkylresorcinols as New Modulators of the Metabolic Activity of the Gut Microbiota.}, journal = {International journal of molecular sciences}, volume = {24}, number = {18}, pages = {}, pmid = {37762509}, issn = {1422-0067}, abstract = {Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db, and LDLR (-/-) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol's regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (-/-) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (-/-) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism.}, }
@article {pmid37761817, year = {2023}, author = {Carapeto, S and Cunha, E and Serrano, I and Pascoal, P and Pereira, M and Abreu, R and Neto, S and Antunes, B and Dias, R and Tavares, L and Oliveira, M}, title = {Effect of the Administration of a Lyophilised Faecal Capsules on the Intestinal Microbiome of Dogs: A Pilot Study.}, journal = {Genes}, volume = {14}, number = {9}, pages = {}, pmid = {37761817}, issn = {2073-4425}, mesh = {Dogs ; Animals ; *Gastrointestinal Microbiome ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; Feces ; Diarrhea ; }, abstract = {Faecal Microbiota Transplantation (FMT) is a promising strategy for modulating the gut microbiome. We aimed to assess the effect of the oral administration of capsules containing lyophilised faeces on dogs with diarrhoea for 2 months as well as evaluate their long-term influence on animals' faecal consistency and intestinal microbiome. This pilot study included five dogs: two used as controls and three with diarrhoea. Animals were evaluated for four months by performing a monthly faecal samples collection and physical examination, which included faecal consistency determination using the Bristol scale. The total number of viable bacteria present in the capsules was quantified and their bacterial composition was determined by 16S rRNA gene sequencing, which was also applied to the faecal samples. During the assay, no side effects were reported. Animals' faecal consistency improved and, after ending capsules administration, Bristol scale values remained stable in two of the three animals. The animals' microbiome gradually changed toward a composition associated with a balanced microbiota. After FMT, a slight shift was observed in its composition, but the capsules' influence remained evident during the 4-month period. Capsules administration seems to have a positive effect on the microbiota modulation; however, studies with more animals should be performed to confirm our observations.}, }
@article {pmid37761327, year = {2023}, author = {Stojic, J and Kukla, M and Grgurevic, I}, title = {The Intestinal Microbiota in the Development of Chronic Liver Disease: Current Status.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {18}, pages = {}, pmid = {37761327}, issn = {2075-4418}, abstract = {Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut-liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut-liver interplay into clinical practice as an additional tool to fight CLD and its complications.}, }
@article {pmid37760856, year = {2023}, author = {Wu, L and Lin, ZH and Lu, XJ and Hu, X and Zhong, HJ and Lin, DJ and Liu, T and Xu, JT and Lin, WY and Wu, QP and He, XX}, title = {Washed Microbiota Transplantation Improves Patients with Overweight by the Gut Microbiota and Sphingolipid Metabolism.}, journal = {Biomedicines}, volume = {11}, number = {9}, pages = {}, pmid = {37760856}, issn = {2227-9059}, support = {2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; B2022209//Medical Scientific Research Foundation of Guangdong Province/ ; 20221232//Scientific Research Projects of Guangdong Bureau of Traditional Chinese Medicine/ ; 2021KCXTD025//Guangdong Innovation Research Team for Higher Education/ ; }, abstract = {BACKGROUND: Overweight (OW) and obesity have become increasingly serious public health problems worldwide. The clinical impact of washed microbiota transplantation (WMT) from healthy donors in OW patients is unclear. This study aimed to investigate the effect of WMT in OW patients.<br><br>METHODS: The changes in body mass index (BMI = weight (kg)/height (m)[2]), blood glucose, blood lipids and other indicators before and after WMT were compared. At the same time, 16S rRNA gene amplicon sequencing was performed on fecal samples of OW patients before and after transplantation. Finally, serum samples were tested for sphingolipids targeted by lipid metabolomics.<br><br>RESULTS: A total of 166 patients were included, including 52 in the OW group and 114 in the normal weight (NOW) group. For OW patients, WMT significantly improved the comprehensive efficacy of OW. In the short term (about 1 month) and medium term (about 2 months), a significant reduction in BMI was seen. At the same time, in the short term (about 1 month), liver fat attenuation (LFA), triglyceride (TG) and fasting blood glucose (FBG) were significantly reduced. In the long term (about 5 months), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein (non-HDL-c), etc. were significantly reduced. WMT improved the gut microbiota of OW patients, and also had an improvement effect on OW patients by regulating sphingolipid metabolism.<br><br>CONCLUSION: WMT had a significant improvement effect on OW patients. WMT could restore gut microbiota homeostasis and improve OW patients by regulating sphingolipid metabolism.}, }
@article {pmid37756370, year = {2024}, author = {Zhou, J and Hao, J and Zhong, Z and Yang, J and Lv, T and Zhao, B and Lin, H and Chi, J and Guo, H}, title = {Fecal Microbiota Transplantation in Mice Exerts a Protective Effect Against Doxorubicin-Induced Cardiac Toxicity by Regulating Nrf2-Mediated Cardiac Mitochondrial Fission and Fusion.}, journal = {Antioxidants &amp; redox signaling}, volume = {41}, number = {1-3}, pages = {1-23}, doi = {10.1089/ars.2023.0355}, pmid = {37756370}, issn = {1557-7716}, mesh = {Animals ; *NF-E2-Related Factor 2/metabolism ; *Fecal Microbiota Transplantation ; Mice ; *Doxorubicin/adverse effects ; *Mitochondrial Dynamics/drug effects ; *Cardiotoxicity ; Gastrointestinal Microbiome/drug effects ; Male ; Reactive Oxygen Species/metabolism ; Oxidative Stress/drug effects ; }, abstract = {Aims: The relationship between the gut microbiota and cardiovascular system has been increasingly clarified. Fecal microbiota transplantation (FMT), used to improve gut microbiota, has been applied clinically for disease treatment and has great potential in combating doxorubicin (DOX)-induced cardiotoxicity. However, the application of FMT in the cardiovascular field and its molecular mechanisms are poorly understood. Results: During DOX-induced stress, FMT alters the gut microbiota and serum metabolites, leading to a reduction in cardiac injury. Correlation analysis indicated a close association between serum metabolite indole-3-propionic acid (IPA) and cardiac function. FMT and IPA achieve this by facilitating the translocation of Nfe2l2 (Nrf2) from the cytoplasm to the nucleus, thereby activating the expression of antioxidant molecules, reducing reactive oxygen species production, and inhibiting excessive mitochondrial fission. Consequently, mitochondrial function is preserved, leading to the mitigation of cardiac injury under DOX-induced stress. Innovation: FMT has the ability to modify the composition of the gut microbiota, providing not only protection to the intestinal mucosa but also influencing the generation of serum metabolites and regulating the Nrf2 gene to modulate the balance of cardiac mitochondrial fission and fusion. This study comprehensively demonstrates the efficacy of FMT in countering DOX-induced myocardial damage and elucidates the pathways linking the microbiota and the heart. Conclusion: FMT alters the gut microbiota and serum metabolites of recipient mice, promoting nuclear translocation of Nrf2 and subsequent activation of downstream antioxidant molecule expression, while inhibiting excessive mitochondrial fission to preserve cardiac integrity. Correlation analysis highlights IPA as a key contributor among differentially regulated metabolites.}, }
@article {pmid37756322, year = {2023}, author = {Stefansson, M and Bladh, O and Flink, O and Skolling, O and Ekre, HP and Rombo, L and Engstrand, L and Ursing, J}, title = {Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0292132}, pmid = {37756322}, issn = {1932-6203}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; Feces ; *Clostridium Infections/therapy/etiology ; *Gastrointestinal Microbiome ; Anti-Bacterial Agents ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is recommended treatment for recurrent Clostridioides difficile infection and is studied as a potential modifier of other gastrointestinal and systemic disorders. Autologous FMT limits the potential risks of donor transplant material and enables prophylactic treatment. Capsulized FMT is convenient and accessible, but safety data are lacking.<br><br>AIMS: To describe safety and tolerability of capsules containing autologous FMT, compared to placebo, in healthy volunteers treated with antibiotics.<br><br>METHOD: Healthy volunteers without antibiotic exposure during the past three months, that had a negative Clostridioides difficile stool sample, were recruited. Study persons donated faeces for production of capsules containing autologous microbiota. They were then given Clindamycin for seven days to disrupt the intestinal microbiota, which was followed by a two-day washout. Study persons were then randomized (1:1) to unsupervised treatment with autologous faecal matter or placebo, with two capsules twice daily for five days. A standardized questionnaire about side effects and tolerability, daily until day 28, and on days 60 and 180, was completed.<br><br>RESULTS: Twenty-four study persons were included, all completed the treatment. One person from the placebo and FMT groups each, were lost to follow up from days 21 and 60, respectively. No study person experienced serious side effects, but severe fatigue was reported during the antibiotic period (n = 2). Reported side effects were mild to moderate and there were no significant differences between the groups. Reported general and intestinal health improved significantly and similarly in both groups after the antibiotic treatment. Time to normalized intestinal habits were 17 and 19 days from study start in the placebo group and the FMT group, respectively (p = 0.8).<br><br>CONCLUSION: Capsulized frozen autologous faecal microbiota transplantation was safe and well tolerated but did not affect time to normalized intestinal habits compared to placebo.<br><br>TRIAL REGISTRATION: EudraCT 2017-002418-30.}, }
@article {pmid37756083, year = {2023}, author = {Rojas, CA and Entrolezo, Z and Jarett, JK and Jospin, G and Kingsbury, DD and Martin, A and Eisen, JA and Ganz, HH}, title = {Microbiome Responses to Fecal Microbiota Transplantation in Cats with Chronic Digestive Issues.}, journal = {Veterinary sciences}, volume = {10}, number = {9}, pages = {}, pmid = {37756083}, issn = {2306-7381}, support = {AB-1001//AnimalBiome/ ; }, abstract = {There is growing interest in the application of fecal microbiota transplants (FMTs) in small animal medicine, but there are few published studies that have tested their effects in the domestic cat (Felis catus). Here we use 16S rRNA gene sequencing to examine fecal microbiome changes in 46 domestic cats with chronic digestive issues that received FMTs using lyophilized stool that was delivered in oral capsules. Fecal samples were collected from FMT recipients before and two weeks after the end of the full course of 50 capsules, as well as from their stool donors (N = 10), and other healthy cats (N = 113). The fecal microbiomes of FMT recipients varied with host clinical signs and dry kibble consumption, and shifts in the relative abundances of Clostridium, Collinsella, Megamonas, Desulfovibrio and Escherichia were observed after FMT. Overall, donors shared 13% of their bacterial amplicon sequence variants (ASVs) with FMT recipients and the most commonly shared ASVs were classified as Prevotella 9, Peptoclostridium, Bacteroides, and Collinsella. Lastly, the fecal microbiomes of cats with diarrhea became more similar to the microbiomes of age-matched and diet-matched healthy cats compared to cats with constipation. Overall, our results suggest that microbiome responses to FMT may be modulated by the FMT recipient's initial presenting clinical signs, diet, and their donor's microbiome.}, }
@article {pmid37754772, year = {2023}, author = {Liu, X and Yang, M and Liu, R and Zhou, F and Zhu, H and Wang, X}, title = {The impact of Parkinson's disease-associated gut microbiota on the transcriptome in Drosophila.}, journal = {Microbiology spectrum}, volume = {11}, number = {5}, pages = {e0017623}, pmid = {37754772}, issn = {2165-0497}, abstract = {Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people, and many studies have confirmed that the disorder of gut microbiota is involved in the pathophysiological process of PD. However, the molecular mechanism of gut microbiota in regulating the pathogenesis of PD is still lacking. In this study, to investigate the impact of PD-associated gut microbiota on host transcriptome, we established various PD models with fecal microbiota transplantation (FMT) in the model organism Drosophila followed by integrative data analysis of microbiome and transcriptome. We first constructed rotenone-induced PD models in Drosophila followed by FMT in different groups. Microbial analysis by 16S rDNA sequencing showed that gut microbiota from PD Drosophila could affect bacterial structure of normal Drosophila, and gut microbiota from normal Drosophila could affect bacterial structure of PD Drosophila. Transcriptome analysis revealed that PD-associated gut microbiota influenced expression patterns of genes enriched in neuroactive ligand-receptor interaction, lysosome, and diverse metabolic pathways. Importantly, to verify our findings, we transplanted Drosophila with fecal samples from clinical PD patients. Compared to the control, Drosophila transplanted with fecal samples from PD patients had reduced microbiota Acetobacter and Lactobacillus, and differentially expressed genes enriched in diverse metabolic pathways. In summary, our results reveal the influence of PD-associated gut microbiota on host gene expression, and this study can help better understand the link between gut microbiota and PD pathogenesis through gut-brain axis. IMPORTANCE Gut microbiota plays important roles in regulating host gene expression and physiology through complex mechanisms. Recently, it has been suggested that disorder of gut microbiota is involved in the pathophysiological process of Parkinson's disease (PD). However, the molecular mechanism of gut microbiota in regulating the pathogenesis of PD is still lacking. In this study, to investigate the impact of PD-associated gut microbiota on host transcriptome, we established various PD models with fecal microbiota transplantation in the model organism Drosophila followed by integrative data analysis of microbiome and transcriptome. We also verified our findings by transplanting Drosophila with fecal samples from clinical PD patients. Our results demonstrated that PD-associated gut microbiota can induce differentially expressed genes enriched in diverse metabolic pathways. This study can help better understand the link between gut microbiota and PD pathogenesis through gut-brain axis.}, }
@article {pmid37754239, year = {2023}, author = {Malnick, SDH and Ohayon Michael, S}, title = {The Intestinal Microbiome and the Metabolic Syndrome-How Its Manipulation May Affect Metabolic-Associated Fatty Liver Disease (MAFLD).}, journal = {Current issues in molecular biology}, volume = {45}, number = {9}, pages = {7197-7211}, pmid = {37754239}, issn = {1467-3045}, abstract = {Metabolic-associated fatty liver disease (MAFLD) is now the predominant liver disease worldwide consequent to the epidemic of obesity. The intestinal microbiome (IM), consisting of the bacteria, fungi, archaea, and viruses residing in the gastrointestinal tract, plays an important role in human metabolism and preserving the epithelial barrier function. Disturbances in the IM have been shown to influence the development and progression of MAFLD and play a role in the development of metabolic syndrome (MS). The main treatment for MAFLD involves lifestyle changes, which also influence the IM. Manipulation of the IM by fecal microbial transplantation (FMT) has been approved for the treatment of recurrent Closteroides difficile infection. This may be administered by endoscopic administration from the lower or upper GI tract. Other methods of administration include nasogastric tube, enema, and oral capsules of stool from healthy donors. In this narrative review, we elaborate on the role of the IM in developing MS and MAFLD and on the current experience with IM modulation by FMT on MAFLD.}, }
@article {pmid37753568, year = {2023}, author = {Liu, Y and Zhang, P and Sheng, H and Xu, D and Li, D and An, L}, title = {16S rRNA gene sequencing and machine learning reveal correlation between drug abuse and human host gut microbiota.}, journal = {Addiction biology}, volume = {28}, number = {10}, pages = {e13311}, doi = {10.1111/adb.13311}, pmid = {37753568}, issn = {1369-1600}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Genes, rRNA ; China ; *Substance-Related Disorders ; Citrates ; }, abstract = {Over the past few years, there has been increasing evidence highlighting the strong connection between gut microbiota and overall well-being of the host. This has led to a renewed emphasis on studying and addressing substance use disorder from the perspective of brain-gut axis. Previous studies have suggested that alcohol, food, and cigarette addictions are strongly linked to gut microbiota and faecal microbiota transplantation or the use of probiotics achieved significant efficacy. Unfortunately, little is known about the relationship between drug abuse and gut microbiota. This paper aims to reveal the potential correlation between gut microbiota and drug abuse and to develop an accurate identification model for drug-related faeces samples by machine learning. Faecal samples were collected from 476 participants from three regions in China (Shanghai, Yunnan, and Shandong). Their gut microbiota information was obtained using 16S rRNA gene sequencing, and a substance use disorder identification model was developed by machine learning. Analysis revealed a lower diversity and a more homogeneous gut microbiota community structure among participants with substance use disorder. Bacteroides, Prevotella_9, Faecalibacterium, and Blautia were identified as important biomarkers associated with substance use disorder. The function prediction analysis revealed that the citrate and reductive citrate cycles were significantly upregulated in the substance use disorder group, while the shikimate pathway was downregulated. In addition, the machine learning model could distinguish faecal samples between substance users and nonsubstance users with an AUC = 0.9, indicating its potential use in predicting and screening individuals with substance use disorder within the community in the future.}, }
@article {pmid37753524, year = {2023}, author = {Ejtahed, HS and Parsa, M and Larijani, B}, title = {Ethical challenges in conducting and the clinical application of human microbiome research.}, journal = {Journal of medical ethics and history of medicine}, volume = {16}, number = {}, pages = {5}, pmid = {37753524}, issn = {2008-0387}, }
@article {pmid37753364, year = {2023}, author = {Gulumbe, BH and Abdulrahim, A}, title = {Pushing the frontiers in the fight against antimicrobial resistance: the potential of fecal and maggot therapies.}, journal = {Future science OA}, volume = {9}, number = {10}, pages = {FSO899}, pmid = {37753364}, issn = {2056-5623}, abstract = {The escalating crisis of antimicrobial resistance (AMR) warrants innovative therapeutic strategies. Fecal microbiota transplantation (FMT) and maggot debridement therapy (MDT) represent paradigm-shifting approaches, leveraging biological systems to mitigate AMR. FMT restores a healthy gut microbiome, providing a biotherapeutic counter to pathogenic bacteria, thereby reducing reliance on traditional antibiotics. Conversely, MDT, a form of bio-debridement, utilizes the antimicrobial secretions of maggots to cleanse wounds and eliminate resistant bacteria. Despite the promise these therapies hold, their broader clinical adoption faces multifaceted challenges including the need for rigorous scientific substantiation, standardized protocols, deepened understanding of mechanisms of action, and surmounting regulatory and public acceptance barriers. However, their potential integration with precision medicine could revolutionize disease management, particularly with antibiotic-resistant infections.}, }
@article {pmid37752615, year = {2023}, author = {Jin, Z and Yang, Y and Cao, Y and Wen, Q and Xi, Y and Cheng, J and Zhao, Q and Weng, J and Hong, K and Jiang, H and Hang, J and Zhang, Z}, title = {The gut metabolite 3-hydroxyphenylacetic acid rejuvenates spermatogenic dysfunction in aged mice through GPX4-mediated ferroptosis.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {212}, pmid = {37752615}, issn = {2049-2618}, mesh = {Mice ; Male ; Animals ; *Ferroptosis ; Semen ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Spermatogenesis ; }, abstract = {BACKGROUND: Aging-related fertility decline is a prevalent concern globally. Male reproductive system aging is mainly characterized by a decrease in sperm quality and fertility. While it is known that intestinal physiology changes with age and that microbiota is shaped by physiology, the underlying mechanism of how the microbiota affects male reproductive aging is still largely unexplored.<br><br>RESULTS: Here, we utilized fecal microbiota transplantation (FMT) to exchange the fecal microbiota between young and old mice. Cecal shotgun metagenomics and metabolomics were used to identify differences in gut microbiota composition and metabolic regulation during aging. Our results demonstrated that FMT from young to old mice alleviated aging-associated spermatogenic dysfunction through an unexpected mechanism mediated by a gut bacteria-derived metabolite, 3-hydroxyphenylacetic acid (3-HPAA). 3-HPAA treatment resulted in an improvement of spermatogenesis in old mice. RNA sequencing analysis, qRT-PCR and Western blot revealed that 3-HPAA induced an upregulation of GPX4, thereby restraining ferroptosis and restoring spermatogenesis. These findings were further confirmed by in vitro induction of ferroptosis and inhibition of GPX4 expression.<br><br>CONCLUSIONS: Our results demonstrate that the microbiome-derived metabolite, 3-HPAA, facilitates spermatogenesis of old mice through a ferroptosis-mediated mechanism. Overall, these findings provide a novel mechanism of dysregulated spermatogenesis of old mice, and suggest that&#xa0;3-HPAA could be a&#xa0;potential therapy for fertility decline of aging males in clinical practice. Video Abstract.}, }
@article {pmid37752426, year = {2023}, author = {Lapauw, L and Dupont, J and Amini, N and Vercauteren, L and Verschueren, S and Tournoy, J and Raes, J and Gielen, E}, title = {Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT): protocol of a cross-sequential study to explore the gut-muscle axis in the development and treatment of sarcopenia in community-dwelling older adults.}, journal = {BMC geriatrics}, volume = {23}, number = {1}, pages = {599}, pmid = {37752426}, issn = {1471-2318}, mesh = {Aged ; Humans ; *Sarcopenia/therapy ; Cross-Sectional Studies ; Independent Living ; Muscles ; Inflammation/therapy ; Feces ; }, abstract = {BACKGROUND: Gut microbiota (GM) might play a role in muscle metabolism and physiological processes through a hypothesized gut-muscle axis, influencing muscle mass and function and thus, sarcopenia. The Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT) aims to explore the gut-muscle axis in sarcopenia.<br><br>METHODS: First, in a cross-sectional case-control phase, 100 community-dwelling adults without sarcopenia will be compared to 100 community-dwelling adults (&#x2265;&#x2009;65&#xa0;years) with sarcopenia of similar age-, gender and BMI-ratio, participating in the ongoing 'Exercise and Nutrition for Healthy AgeiNg' (ENHANce; NCT03649698) study. Sarcopenia is diagnosed according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. GM composition and intestinal inflammatory markers (fecal calprotectin, lactoferrin and S100A12) will be determined in fecal samples. Systemic inflammatory markers (hs-CRP, IL-4, IL-6, TNF-&#x3b1;, IL-13, IL-1&#x3b2; and creatine kinase) will be determined in fasted blood samples. Both groups will be compared using appropriate statistical testing, whereas linear regression will be used for cross-sectional associations between gut, inflammatory and sarcopenia parameters. Second, in the longitudinal phase, sarcopenic older adults will be requested to deliver five fecal samples during the 12-week intervention to assess the effects of protein, omega-3 and a physical exercise program on the GM.<br><br>DISCUSSION: TEMPUS-FUGIT aims to explore the gut-muscle axis by comparing GM composition between sarcopenic and non-sarcopenic older adults and to determine the association of GM with intestinal and systemic inflammatory markers and sarcopenia-defining parameters (muscle mass, muscle strength and physical performance). Furthermore, effects of single or combined, optimized and individualized anabolic interventions (exercise, protein and omega-3 supplementation), on GM will be explored in persons with sarcopenia. TEMPUS-FUGIT aims to impact clinical practice by clarifying the relationship between the gut-muscle axis and sarcopenia. TEMPUS-FUGIT is expected to contribute to the discovery of clinical and microbial biomarkers for sarcopenia and insights in its pathophysiology, opening possible future perspectives for novel sarcopenia treatment strategies targeting GM.<br><br>TRIAL REGISTRATION: ClinicalTrails.gov NCT05008770, registered on August 17, 2021; first participant enrolled on September 21 2021.}, }
@article {pmid37752225, year = {2023}, author = {Luo, Y and Liu, C and Luo, Y and Zhang, X and Li, J and Hu, C and Yang, S}, title = {Thiostrepton alleviates experimental colitis by promoting RORγt ubiquitination and modulating dysbiosis.}, journal = {Cellular &amp; molecular immunology}, volume = {20}, number = {11}, pages = {1352-1366}, pmid = {37752225}, issn = {2042-0226}, mesh = {Animals ; Mice ; *Interleukin-17/metabolism ; Thiostrepton/metabolism/pharmacology/therapeutic use ; Immunity, Innate ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; Dysbiosis ; Lymphocytes/metabolism ; *Colitis/chemically induced/therapy ; Colon/metabolism ; Inflammation/metabolism ; Ubiquitination ; Dextran Sulfate ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {Thiostrepton (TST) is a natural antibiotic with pleiotropic properties. This study aimed to elucidate the therapeutic effect of TST on experimental colitis and identify its targets. The effect of TST on colon inflammation was evaluated in a dextran sulfate sodium (DSS)-induced colitis model and a T-cell transfer colitis model. The therapeutic targets of TST were investigated by cytokine profiling, immunophenotyping and biochemical approaches. The effect of TST on the gut microbiota and its contribution to colitis were evaluated in mice with DSS-induced colitis that were subjected to gut microbiota depletion and fecal microbiota transplantation (FMT). Alterations in the gut microbiota caused by TST were determined by 16S rDNA and metagenomic sequencing. Here, we showed that TST treatment significantly ameliorated colitis in the DSS-induced and T-cell transfer models. Specifically, TST targeted the retinoic acid-related orphan nuclear receptor RORγt to reduce the production of IL-17A by γδ T cells, type 3 innate lymphoid cells (ILC3s) and Th17 cells in mice with DSS-induced colitis. Similarly, TST selectively prevented the development of Th17 cells in the T-cell transfer colitis model and the differentiation of naïve CD4[+] T cells into Th17 cells in vitro. Mechanistically, TST induced the ubiquitination and degradation of RORγt by promoting the binding of Itch to RORγt. Moreover, TST also reversed dysbiosis to control colonic inflammation. Taken together, these results from our study describe the previously unexplored role of TST in alleviating colonic inflammation by reducing IL-17A production and modulating dysbiosis, suggesting that TST is a promising candidate drug for the treatment of IBD.}, }
@article {pmid37750481, year = {2023}, author = {Gryschek, RCB and Corral, MA and Sitta, RB and Gottardi, M and Pierrotti, LC and Costa, SF and Abdala, E and Chieffi, PP and de Paula, FM}, title = {Strongyloides infection screening in transplant candidates: What is the best strategy?.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {25}, number = {6}, pages = {e14153}, doi = {10.1111/tid.14153}, pmid = {37750481}, issn = {1399-3062}, support = {2010/51110-2//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do EStado de S&#xe3;o Paulo (FAPESP)/ ; 2013/04236-9//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do EStado de S&#xe3;o Paulo (FAPESP)/ ; }, mesh = {Animals ; Humans ; *Strongyloidiasis/diagnosis ; *Strongyloides stercoralis/genetics ; Mass Screening ; Polymerase Chain Reaction ; Enzyme-Linked Immunosorbent Assay/methods ; Feces ; }, abstract = {BACKGROUND: The potential that Strongyloides stercoralis infection has to cause major morbidity and high mortality when the disseminated form occurs in transplant patients is of particular concern.<br><br>METHODS: In this study, the objective was to observe S. stercoralis infection in patients who are candidates for transplantation by using parasitological, serological, and molecular techniques and to propose an algorithm for the detection of that infection in transplant candidates.<br><br>RESULTS: By parasitological techniques, 10% of fecal samples were positive. Anti-Strongyloides antibodies immunoglobulin G were detected in 19.3% and 20.7% of patients by immunofluorescence assay and enzyme-linked immunosorbent assay, respectively. S. stercoralis DNA was observed in 17.3% of samples by conventional polymerase chain reaction and 32.7% of samples by quantitative polymerase chain reaction (qPCR).<br><br>CONCLUSION: The set of results allows us to reinforce that a positive result by parasitological techniques and/or qPCR indicates that the specific treatment should be applied. However, the improvement of diagnostic techniques may suggest changes in the screening for strongyloidiasis in these patients.}, }
@article {pmid37749611, year = {2023}, author = {Liu, A and Liang, X and Wang, W and Wang, C and Song, J and Guo, J and Sun, D and Wang, D and Song, M and Qian, J and Zhang, X}, title = {Human umbilical cord mesenchymal stem cells ameliorate colon inflammation via modulation of gut microbiota-SCFAs-immune axis.}, journal = {Stem cell research &amp; therapy}, volume = {14}, number = {1}, pages = {271}, pmid = {37749611}, issn = {1757-6512}, mesh = {Humans ; *Gastrointestinal Microbiome ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; *Colitis/chemically induced/therapy ; *Inflammatory Bowel Diseases ; *Mesenchymal Stem Cells ; Fatty Acids, Volatile ; Inflammation ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has emerged as a prospective novel tool for managing IBD, and which can also regulate the composition of gut microbiota. However, the functional significance of MSCs-induced changes in gut microbiome is poorly understood.<br><br>METHODS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of human umbilical cord MSCs (HUMSCs) on DSS-induced colitis. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Spectrum antibiotic cocktail (ABX), fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) were employed to evaluate the protective effect of intestinal flora and its metabolites. Cytokine microarray, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry were conducted to assess the effect on CD4[+]T homeostasis.<br><br>RESULTS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of MSCs on DSS-induced colitis. By performing gut microbiota depletion and fecal microbiota transplantation (FMT) experiments, we revealed that MSCs derived from human umbilical cord ameliorated colon inflammation and reshaped T-cells immune homeostasis via remodeling the composition and diversity of gut flora, especially up-regulated SCFAs-producing bacterial abundance, such as Akkermansia, Faecalibaculum, and Clostridia_UCG_014. Consistently, targeted metabolomics manifested the increased SCFAs production with MSCs administration, and there was also a significant positive correlation between differential bacteria and SCFAs. Meanwhile, combined with sterile fecal filtrate (SFF) gavage experiments, the underlying protective mechanism was further associated with the improved Treg/Th2/Th17 balance in intestinal mucosa mediated via the increased microbiota-derived SCFAs production.<br><br>CONCLUSION: The present study advances understanding of MSCs in the protective effects on colitis, providing evidence for the new role of the microbiome-metabolite-immune axis in the recovery of colitis by MSCs.}, }
@article {pmid37746903, year = {2023}, author = {Verhoef, JI and Klont, E and van Overveld, FJ and Rijkers, GT}, title = {The long and winding road of faecal microbiota transplants to targeted intervention for improvement of immune checkpoint inhibition therapy.}, journal = {Expert review of anticancer therapy}, volume = {23}, number = {11}, pages = {1179-1191}, doi = {10.1080/14737140.2023.2262765}, pmid = {37746903}, issn = {1744-8328}, mesh = {Humans ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/pharmacology ; Butyrates/metabolism ; *Gastrointestinal Microbiome ; *Neoplasms ; }, abstract = {INTRODUCTION: Immune checkpoint inhibition (ICI) therapy has revolutionized the treatment of cancer. Inhibitory molecules, either on the tumor or on cells of the immune system, are blocked, allowing the immune system of the patient to attack and eradicate the tumor. Not all patients respond to ICI therapy, and response or non-response has been associated with composition of gut microbiota.<br><br>AREA COVERED: Fecal microbiota transplantation (FMT) is used as adjunctive therapy in order to improve the outcome of ICI. ClinicalTrials.gov, and other databases were searched (October 2022) for studies dealing with gut microbiota modification and the outcome of ICI.<br><br>EXPERT OPINION: There is ample evidence for the beneficial effect of FMT on the outcome of ICI therapy for cancer, especially melanoma. Progress is being made in the unraveling of the mechanisms by which microbiota and their metabolites (butyrate and the tryptophan metabolite indole-3-aldehyde) interact with the mucosal immune system of the host. A better understanding of the mechanisms involved will allow the identification of key bacterial species which mediate the effect of FMT. Promising species are Faecalibacterium prausnitzii, Eubacterium rectale, Bifidobacterium adolescentis, B. bifidum, and B. longum, because they are important direct and indirect butyrate producers.}, }
@article {pmid37743861, year = {2023}, author = {Hu, X and Jin, H and Yuan, S and Ye, T and Chen, Z and Kong, Y and Liu, J and Xu, K and Sun, J}, title = {Fecal microbiota transplantation inhibited neuroinflammation of traumatic brain injury in mice via regulating the gut-brain axis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1254610}, pmid = {37743861}, issn = {2235-2988}, mesh = {Animals ; Mice ; *Brain-Gut Axis ; Neuroinflammatory Diseases ; Fecal Microbiota Transplantation ; *Brain Injuries, Traumatic/therapy ; Cytokines ; Disease Models, Animal ; }, abstract = {INTRODUCTION: Recent studies have highlighted the vital role of gut microbiota in traumatic brain injury (TBI). Fecal microbiota transplantation (FMT) is an effective means of regulating the microbiota-gut-brain axis, while the beneficial effect and potential mechanisms of FMT against TBI remain unclear. Here, we elucidated the anti-neuroinflammatory effect and possible mechanism of FMT against TBI in mice via regulating the microbiota-gut-brain axis.<br><br>METHODS: The TBI mouse model was established by heavy object falling impact and then treated with FMT. The neurological deficits, neuropathological change, synaptic damage, microglia activation, and neuroinflammatory cytokine production were assessed, and the intestinal pathological change and gut microbiota composition were also evaluated. Moreover, the population of Treg cells in the spleen was measured.<br><br>RESULTS: Our results showed that FMT treatment significantly alleviated neurological deficits and neuropathological changes and improved synaptic damage by increasing the levels of the synaptic plasticity-related protein such as postsynaptic density protein 95 (PSD-95) and synapsin I in the TBI mice model. Moreover, FMT could inhibit the activation of microglia and reduce the production of the inflammatory cytokine TNF-&#x3b1;, alleviating the inflammatory response of TBI mice. Meanwhile, FMT treatment could attenuate intestinal histopathologic changes and gut microbiota dysbiosis and increase the Treg cell population in TBI mice.<br><br>CONCLUSION: These findings elucidated that FMT treatment effectively suppressed the TBI-induced neuroinflammation via regulating the gut microbiota-gut-brain axis, and its mechanism was involved in the regulation of peripheral immune cells, which implied a novel strategy against TBI.}, }
@article {pmid37742728, year = {2023}, author = {Ciernikova, S and Sevcikova, A and Drgona, L and Mego, M}, title = {Modulating the gut microbiota by probiotics, prebiotics, postbiotics, and fecal microbiota transplantation: An emerging trend in cancer patient care.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {1878}, number = {6}, pages = {188990}, doi = {10.1016/j.bbcan.2023.188990}, pmid = {37742728}, issn = {1879-2561}, mesh = {Humans ; Prebiotics ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; *Neoplasms/therapy/microbiology ; Patient Care ; }, abstract = {Treatment resistance, together with acute and late adverse effects, represents critical issues in the management of cancer patients. Promising results from preclinical and clinical research underline the emerging trend of a microbiome-based approach in oncology. Favorable bacterial species and higher gut diversity are associated with increased treatment efficacy, mainly in chemo- and immunotherapy. On the other hand, alterations in the composition and activity of gut microbial communities are linked to intestinal dysbiosis and contribute to high treatment-induced toxicity. In this Review, we provide an overview of studies concerning gut microbiota modulation in patients with solid and hematologic malignancies with a focus on probiotics, prebiotics, postbiotics, and fecal microbiota transplantation. Targeting the gut microbiome might bring clinical benefits and improve patient outcomes. However, a deeper understanding of mechanisms and large clinical trials concerning microbiome and immunological profiling is warranted to identify safe and effective ways to incorporate microbiota-based interventions in routine clinical practice.}, }
@article {pmid37741298, year = {2023}, author = {Liu, Z and Sun, M and Jin, C and Sun, X and Feng, F and Niu, X and Wang, B and Zhang, Y and Wang, J}, title = {Naringenin confers protection against experimental autoimmune encephalomyelitis through modulating the gut-brain axis: A multiomics analysis.}, journal = {The Journal of nutritional biochemistry}, volume = {122}, number = {}, pages = {109448}, doi = {10.1016/j.jnutbio.2023.109448}, pmid = {37741298}, issn = {1873-4847}, mesh = {Mice ; Animals ; *Encephalomyelitis, Autoimmune, Experimental/drug therapy/prevention &amp; control ; Brain-Gut Axis ; RNA, Ribosomal, 16S/genetics ; Multiomics ; *Multiple Sclerosis/pathology ; }, abstract = {Multiple sclerosis (MS) is a disease of the central nervous system that involves the immune system attacking the protective covering of nerve fibers. This disease can be influenced by both environmental and genetic factors. Evidence has highlighted the critical role of the intestinal microbiota in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). The composition of gut microflora is mainly determined by dietary components, which, in turn, modulate host homeostasis. A diet rich in naringenin at 0.5% can effectively mitigate the severity of EAE in mice. However, there is little direct data on the impact of naringenin at optimal doses on EAE development, as well as its intestinal microbiota and metabolites. Our study revealed that 2.0% naringenin resulted in the lowest clinical score and pathological changes in EAE mice, and altered the gene expression profiles associated with inflammation and immunity in spinal cord tissue. We then used untargeted metabolomics and 16S rRNA gene sequences to identify metabolites and intestinal microbiota, respectively. Naringenin supplementation enriched gut microbiota in EAE mice, including increasing the abundance of Paraprevotellaceae and Comamonadaceae, while decreasing the abundance of Deltaproteobacteria, RF39, and Desulfovibrionaceae. Furthermore, the changes in gut microbiota affected the production of metabolites in the feces and brain, suggesting a role in regulating the gut-brain axis. Finally, we conducted a fecal transplantation experiment to validate that gut microbiota partly mediates the effect of naringenin on EAE alleviation. In conclusion, naringenin has potential immunomodulatory effects that are influenced to some extent by the gut microbiome.}, }
@article {pmid37741061, year = {2023}, author = {Yue, C and Luan, W and Gu, H and Qiu, D and Ding, X and Liu, P and Wang, X and Hashimoto, K and Yang, JJ}, title = {The role of the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve in chronic inflammatory pain and comorbid spatial working memory impairment in complete Freund's adjuvant mice.}, journal = {Journal of psychiatric research}, volume = {166}, number = {}, pages = {61-73}, doi = {10.1016/j.jpsychires.2023.09.003}, pmid = {37741061}, issn = {1879-1379}, mesh = {Mice ; Animals ; Freund's Adjuvant ; Memory, Short-Term ; RNA, Ribosomal, 16S ; *Chronic Pain ; Hyperalgesia ; *Microbiota ; Memory Disorders ; Brain ; Vagus Nerve ; }, abstract = {Chronic inflammatory pain (CIP) is a common public medical problem, often accompanied by memory impairment. However, the mechanisms underlying CIP and comorbid memory impairment remain elusive. This study aimed to examine the role of the gut-microbiota-brain axis in CIP and comorbid memory impairment in mice treated with complete Freund's adjuvant (CFA). 16S rRNA analysis showed the altered diversity of gut microbiota from day 1 to day 14 after CFA injection. Interestingly, fecal microbiota transplantation (FMT) from healthy naive mice ameliorated comorbidities, such as mechanical allodynia, thermal hyperalgesia, spatial working memory impairment, neuroinflammation, and abnormal composition of gut microbiota in the CFA mice. Additionally, subdiaphragmatic vagotomy (SDV) blocked the onset of these comorbidities. Interestingly, the relative abundance of the bacterial genus or species was also correlated with these comorbidities after FMT or SDV. Therefore, our results suggest that the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve is crucial for the development of CIP and comorbid spatial working memory impairment in CFA mice.}, }
@article {pmid37736702, year = {2023}, author = {Kragsnaes, MS and Miguens Blanco, J and Mullish, BH and Serrano-Contreras, JI and Kjeldsen, J and Horn, HC and Pedersen, JK and Munk, HL and Nilsson, AC and Salam, A and Lewis, MR and Chekmeneva, E and Kristiansen, K and Marchesi, JR and Ellingsen, T}, title = {Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial.}, journal = {ACR open rheumatology}, volume = {5}, number = {11}, pages = {583-593}, pmid = {37736702}, issn = {2578-5745}, support = {21228/VAC_/Versus Arthritis/United Kingdom ; }, abstract = {OBJECTIVE: We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate-treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT).<br><br>METHODS: This exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate-treatment, were included in a 26-week, double-blind, 1:1 randomized, sham-controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n&#xa0;=&#xa0;15) or sham (n&#xa0;=&#xa0;16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26&#x2009;weeks. We performed a lactulose-to-mannitol ratio (LMR) test at baseline (n&#xa0;=&#xa0;31) and at week 26 (n&#xa0;=&#xa0;26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using [1] H Nuclear Magnetic Resonance.<br><br>RESULTS: Trial failures (n&#xa0;=&#xa0;7) had significantly higher LMR compared with responders (n&#xa0;=&#xa0;19) at week 26 (0.027 [0.017-0.33]) vs. 0.012 [0-0.064], P =&#x2009;0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n&#xa0;=&#xa0;19) versus failures (n&#xa0;=&#xa0;12) at all time points based on their fecal (P <&#x2009;0.0001) and plasma (P =&#x2009;0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P =&#x2009;1). Fecal N-acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient&#xa0;=&#xa0;0.50; P =&#x2009;0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient&#xa0;=&#xa0;27, P =&#x2009;0.02).<br><br>CONCLUSION: Intestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.}, }
@article {pmid37734581, year = {2024}, author = {Yau, YK and Lau, LHS and Lui, RNS and Wong, SH and Guo, CL and Mak, JWY and Ching, JYL and Ip, M and Kamm, MA and Rubin, DT and Chan, PKS and Chan, FKL and Ng, SC}, title = {Long-Term Safety Outcomes of Fecal Microbiota Transplantation: Real-World Data Over 8 Years From the Hong Kong FMT Registry.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {22}, number = {3}, pages = {611-620.e12}, doi = {10.1016/j.cgh.2023.09.001}, pmid = {37734581}, issn = {1542-7714}, mesh = {Humans ; Male ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Female ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces ; Hong Kong ; Prospective Studies ; *Diabetes Mellitus, Type 2 ; *Clostridioides difficile ; Treatment Outcome ; Recurrence ; *Clostridium Infections/therapy ; }, abstract = {BACKGROUND AND AIMS: Prospective long-term real-world safety data after fecal microbiota transplantation (FMT) remain limited. We reported long-term outcomes of FMT from a population-based FMT registry in Hong Kong.<br><br>METHODS: We recruited patients undergoing FMT for recurrent Clostridioides difficile infection (CDI) and non-CDI indications from clinical trials, from June 2013 to April 2022 in Hong Kong. We captured data on demographics, FMT indications and procedures, clinical outcomes and short- to long-term safety. New medical diagnoses were obtained from electronic medical records and independently adjudicated by clinicians. Long-term safety in patients with recurrent CDI was compared with a control group treated with antibiotics.<br><br>RESULTS: Overall, 123 subjects (median age 53 years, range 13-90 years; 52.0% male) underwent 510 FMTs and were prospectively followed up for a median of 30.3 (range, 1-57.9) months. The most common indication for FMT was type 2 diabetes mellitus. The most common short-term adverse events within 1 month of FMT included diarrhea and abdominal pain. At long-term follow-up beyond 12 months, 16 patients reported 21 new-onset medical conditions confirmed by electronic medical records. All were adjudicated to be unlikely to be related to FMT. There was no new case of inflammatory bowel disease, irritable bowel syndrome, allergy, diabetes mellitus, or psychiatric disorder. In a subgroup of patients with recurrent CDI, FMT was associated with a significantly higher cumulative survival probability compared with matched control subjects.<br><br>CONCLUSIONS: This prospective real-world data from Asia's first FMT registry demonstrated that FMT has an excellent long-term safety profile. The risk of developing new medical conditions beyond 12 months after FMT is low.}, }
@article {pmid37733476, year = {2024}, author = {Kashyap, Y and Wang, ZJ}, title = {Gut microbiota dysbiosis alters chronic pain behaviors in a humanized transgenic mouse model of sickle cell disease.}, journal = {Pain}, volume = {165}, number = {2}, pages = {423-439}, pmid = {37733476}, issn = {1872-6623}, support = {R35 HL140031/HL/NHLBI NIH HHS/United States ; R35 HL140021/HL/NHLBI NIH HHS/United States ; }, mesh = {Mice ; Animals ; Humans ; Mice, Transgenic ; *Chronic Pain ; Hyperalgesia ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; Anti-Bacterial Agents ; *Anemia, Sickle Cell/complications ; }, abstract = {Pain is the most common symptom experienced by patients with sickle cell disease (SCD) throughout their lives and is the main cause of hospitalization. Despite the progress that has been made towards understanding the disease pathophysiology, major gaps remain in the knowledge of SCD pain, the transition to chronic pain, and effective pain management. Recent evidence has demonstrated a vital role of gut microbiota in pathophysiological features of SCD. However, the role of gut microbiota in SCD pain is yet to be explored. We sought to evaluate the compositional differences in the gut microbiota of transgenic mice with SCD and nonsickle control mice and investigate the role of gut microbiota in SCD pain by using antibiotic-mediated gut microbiota depletion and fecal material transplantation (FMT). The antibiotic-mediated gut microbiota depletion did not affect evoked pain but significantly attenuated ongoing spontaneous pain in mice with SCD. Fecal material transplantation from mice with SCD to wild-type mice resulted in tactile allodynia (0.95 ± 0.17 g vs 0.08 ± 0.02 g, von Frey test, P < 0.001), heat hyperalgesia (15.10 ± 0.79 seconds vs 8.68 ± 1.17 seconds, radiant heat, P < 0.01), cold allodynia (2.75 ± 0.26 seconds vs 1.68 ± 0.08 seconds, dry ice test, P < 0.01), and anxiety-like behaviors (Elevated Plus Maze Test, Open Field Test). On the contrary, reshaping gut microbiota of mice with SCD with FMT from WT mice resulted in reduced tactile allodynia (0.05 ± 0.01 g vs 0.25 ± 0.03 g, P < 0.001), heat hyperalgesia (5.89 ± 0.67 seconds vs 12.25 ± 0.76 seconds, P < 0.001), and anxiety-like behaviors. These findings provide insights into the relationship between gut microbiota dysbiosis and pain in SCD, highlighting the importance of gut microbial communities that may serve as potential targets for novel pain interventions.}, }
@article {pmid37731574, year = {2023}, author = {Zyoud, SH and Shakhshir, M and Abushanab, AS and Koni, A and Shahwan, M and Jairoun, AA and Abu Taha, A and Al-Jabi, SW}, title = {Unveiling the hidden world of gut health: Exploring cutting-edge research through visualizing randomized controlled trials on the gut microbiota.}, journal = {World journal of clinical cases}, volume = {11}, number = {26}, pages = {6132-6146}, pmid = {37731574}, issn = {2307-8960}, abstract = {BACKGROUND: The gut microbiota plays a crucial role in gastrointestinal and overall health. Randomized clinical trials (RCTs) play a crucial role in advancing our knowledge and evaluating the efficacy of therapeutic interventions targeting the gut microbiota.<br><br>AIM: To conduct a comprehensive bibliometric analysis of the literature on RCTs involving the gut microbiota.<br><br>METHODS: Using bibliometric tools, a descriptive cross-sectional investigation was conducted on scholarly publications concentrated on RCTs related to gut microbiota, spanning the years 2003 to 2022. The study used VOSviewer version 1.6.9 to examine collaboration networks between different countries and evaluate the frequently employed terms in the titles and abstracts of the retrieved publications. The primary objective of this analysis was to identify key research areas and focal points associated with RCTs involving the gut microbiota.<br><br>RESULTS: A total of 1061 relevant articles were identified from the 24758 research articles published between 2003 and 2022. The number of publications showed a notable increase over time, with a positive correlation (R[2] = 0.978, P < 0.001). China (n = 276, 26.01%), the United States (n = 254, 23.94%), and the United Kingdom (n = 97, 9.14%) were the leading contributing countries. K&#xf8;benhavns Universitet (n = 38, 3.58%) and Dankook University (n = 35, 3.30%) were the top active institutions. The co-occurrence analysis shows current gut microbiota research trends and important topics, such as obesity interventions targeting the gut microbiota, the efficacy and safety of fecal microbiota transplantation, and the effects of dietary interventions on humans.<br><br>CONCLUSION: The study highlights the rapid growth and importance of research on RCTs that involve the gut microbiota. This study provides valuable insight into research trends, identifies key players, and outlines potential future directions in this field. Additionally, the co-occurrence analysis identified important topics that play a critical role in the advancement of science and provided insights into future research directions in this field.}, }
@article {pmid37730588, year = {2023}, author = {Wang, H and Liu, S and Xie, L and Wang, J}, title = {Gut microbiota signature in children with autism spectrum disorder who suffered from chronic gastrointestinal symptoms.}, journal = {BMC pediatrics}, volume = {23}, number = {1}, pages = {476}, pmid = {37730588}, issn = {1471-2431}, mesh = {Female ; Male ; Child ; Humans ; Child, Preschool ; *Gastrointestinal Microbiome ; *Autism Spectrum Disorder ; *Microbiota ; Anxiety ; Constipation ; }, abstract = {BACKGROUND: Children diagnosed with autism spectrum disorder (ASD) frequently suffer from persistent gastrointestinal symptoms, such as constipation and diarrhea. Various studies have highlighted differences in gut microbiota composition between individuals with ASD and healthy controls of similar ages. However, it's essential to recognize that these disparities may be influenced by cultural practices, dietary habits, and environmental factors.<br><br>METHODS: In this study, we collected fecal samples from both children diagnosed with ASD (n&#x2009;=&#x2009;42) and healthy individuals (n&#x2009;=&#x2009;41) residing in the southeastern coastal region of China. Subsequently, 16&#xa0;S rRNA gene sequencing and advanced bioinformatics analyses were conducted to investigate the distinctive features of gut microbial communities within each group.<br><br>RESULTS: The ASD group consisted of 28 males and 14 females, with a median age of 5.8 years, while the control group included 25 males and 16 females, with a median age of 6.8 years. Among the 83 sequenced fecal samples, a total of 1031 operational taxonomic units (OTUs) were identified. These included 122 unique OTUs specific to the control group and 285 unique OTUs specific to the ASD group. Analyses of &#x3b1;-diversity and &#x3b2;-diversity unveiled significant differences in the abundance and composition of gut microbiota between the two groups. It was found that the dominant bacterial taxa in healthy individuals were UBA1819, Flavonifractor, and Bradyrhizobium. In contrast, the ASD group exhibited a prevalence of Streptococcus, Ruminococcus, and Ruminiclostridium. Further analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) showed significant differences in the metabolic functionalities of the gut microbiota between the two groups. Notably, the metabolic pathway related to alpha-linolenic acid (ALA) in the gut microbiota of the ASD group was notably diminished compared to the control group. Conversely, the ASD group demonstrated significantly elevated levels of metabolic pathways involving uncharacterized conserved proteins, aminoglycoside phosphotransferase, and inorganic pyrophosphatase compared to the control group.<br><br>CONCLUSIONS: Overall, these results confirm that there are significant differences in the gut microbiota structure between children with ASD and healthy controls in the southeast coastal region of China. This underscores the critical significance of delving into clinical interventions capable of mitigating the gastrointestinal and psychological symptoms encountered by children with ASD. A particularly encouraging path for such interventions lies in the realm of fecal microbiota transplantation, a prospect that merits deeper inquiry.}, }
@article {pmid37727718, year = {2023}, author = {Del Giglio, A and Atui, FC}, title = {Fecal transplantation in patient with metastatic melanoma refractory to immunotherapy: A case report.}, journal = {World journal of clinical cases}, volume = {11}, number = {24}, pages = {5830-5834}, pmid = {37727718}, issn = {2307-8960}, abstract = {BACKGROUND: Immunotherapy has revolutionized the treatment of metastatic melanoma, but a significant proportion of patients still experience treatment resistance. Fecal microbiota transplantation (FMT) has emerged as a potential strategy to overcome immunotherapy resistance by modulating the gut microbiome.<br><br>CASE SUMMARY: We present a case report of a 57-year-old male with metastatic melanoma refractory to immunotherapy who received FMT in combination with anti-programmed death-ligand 1 (PD-L1) immunotherapy (pembrolizumab). After failing multiple lines of treatment, the patient underwent a single FMT procedure by colonoscopy using fecal material from a female metastatic melanoma donor who successfully responded to immunotherapy. Following FMT, the patient demonstrated a response with decreased subcutaneous disease and subsequently underwent surgery to remove the residual disease. Despite a subsequent recurrence in the small bowel that was resected, the patient remained on pembrolizumab without evidence of melanoma recurrence at the time of writing.<br><br>CONCLUSION: The favorable clinical and long-lasting effect we saw in our patient without significant toxicity suggests that this procedure should be considered in similar patients with immunotherapy refractory melanomas.}, }
@article {pmid37727287, year = {2023}, author = {Li, Y and Li, X and Nie, C and Wu, Y and Luo, R and Chen, C and Niu, J and Zhang, W}, title = {Effects of two strains of Lactobacillus isolated from the feces of calves after fecal microbiota transplantation on growth performance, immune capacity, and intestinal barrier function of weaned calves.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1249628}, pmid = {37727287}, issn = {1664-302X}, abstract = {INTRODUCTION: Weaning stress seriously affects the welfare of calves and causes huge economic losses to the cattle breeding industry. Probiotics play an important role in improving animal growth performance, enhancing immune function, and improving gut microbiota. The newly isolated strains of Lactobacillus reuteri L81 and Lactobacillus johnsonii L29 have shown potential as probiotics. Here, we studied the probiotic properties of these two strains on weaned calves.<br><br>METHODS: Forty calves were randomly assigned to four groups before weaning, with 10 calves in each group, control group (Ctrl group), L. reuteri L81 supplementation group (2 g per day per calf), L. johnsonii L29 supplementation group (2 g per day per calf), L. reuteri L81 and L. johnsonii L29 composite group (2 g per day per calf), and the effects of Lactobacillus reuteri L81 and Lactobacillus johnsonii L29 supplementation on growth performance, immune status, antioxidant capacity, and intestinal barrier function of weaned calves were evaluated.<br><br>RESULTS: The results showed that probiotics supplementation increased the average daily weight gain of calves after weaning, reduced weaning diarrhea index (p&#x2009;<&#x2009;0.05), and increased serum IgA, IgM, and IgG levels (p&#x2009;<&#x2009;0.05). L. reuteri L81 supplementation significantly decreased IL-6, increased IL-10 and superoxide dismutase (SOD) levels at 21 d after weaning (p&#x2009;<&#x2009;0.05). Moreover, probiotics supplementation significantly decreased serum endotoxin (ET), diamine oxidase (DAO), and D-lactic acid (D-LA) levels at different time points (p&#x2009;<&#x2009;0.05). In addition, supplementation with L. reuteri L81 significantly reduced the crypt depth and increased the ratio of villus height to crypt depth (p&#x2009;<&#x2009;0.05) in the ileum, increased gene expression of tight junction protein ZO-1, Claudin-1 and Occludin in jejunum and ileum mucosa, reduced the gene expression of INF- &#x3b3; in ileum mucosa and IL-8 in jejunum mucosa, and increased the abundance of beneficial bacteria, including Bifidobacterium, Lactobacillus, Oscillospira, etc.<br><br>DISCUSSION: verall, these results showed that the two strains isolated from cattle feces after low concentration fecal microbiota transplantation improved the growth performance, immune performance, antioxidant capacity, and intestinal barrier function of weaned calves, indicating their potential as supplements to alleviate weaning diarrhea in calves.}, }
@article {pmid37725892, year = {2023}, author = {Shang, S and Zhu, J and Liu, X and Wang, W and Dai, T and Wang, L and Li, B}, title = {The Impacts of Fecal Microbiota Transplantation from Same Sex on the Symptoms of Ulcerative Colitis Patients.}, journal = {Polish journal of microbiology}, volume = {72}, number = {3}, pages = {247-268}, pmid = {37725892}, issn = {2544-4646}, mesh = {Adolescent ; Humans ; Female ; Male ; *Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; Prospective Studies ; RNA, Ribosomal, 16S ; Abdominal Pain ; Bifidobacterium ; Diarrhea ; *Fabaceae ; Lactobacillus ; }, abstract = {We aimed to compare the clinical efficacy of fecal microbiota transplantation (FMT) from the same sex on ulcerative colitis (UC) patients. A total of 272 UC patients were selected in the prospective clinical study, which incorporated four distinct groups, each comprising male and female patients, who were either receiving FMT or placebo, respectively. FMT was performed by sending the gut microbiota of healthy female or male adolescents to the same gender patients via gastroscope three times (one time/three weeks), and a placebo was used with an equal volume of saline. Abdominal pain, diarrhea, thick bloody stool, intestinal mucosal lesion, and Mayo scores were measured. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were evaluated. The changes of intestinal flora were detected by the 16S rRNA sequencing. FMT reduced the scores of diarrhea, abdominal pain, mucosal lesion, and Mayo, SAS, and SDS in UC patients compared to the placebo group (p < 0.05). Clostridiales and Desulfovibrionaceae were dominant in gut microbiota from male patients and were reduced after FMT. Meanwhile, the abundance of Prevotella, Lactobacillus, and Bifidobacterium was increased in the male group. Female patients had a higher abundance of Escherichia-Shigella, Desulfovibrionaceae, and Staphylococcaceae before FMT, and it was reduced after FMT. Meanwhile, the abundance of Porphyromonadaceae, Prevotella, Lactobacillus, and Bifidobacterium was increased in the female group. There were no significant changes for the species in the corresponding placebo groups. FMT improved the UC symptoms of male and female patients, which may be associated with different gut microbiota changes.}, }
@article {pmid37721283, year = {2024}, author = {Cui, Y and Liu, J and Lei, X and Liu, S and Chen, H and Wei, Z and Li, H and Yang, Y and Zheng, C and Li, Z}, title = {Dual-directional regulation of spinal cord injury and the gut microbiota.}, journal = {Neural regeneration research}, volume = {19}, number = {3}, pages = {548-556}, pmid = {37721283}, issn = {1673-5374}, abstract = {There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis. The spinal cord is a vital important part of the central nervous system; however, the underlying association between spinal cord injury and gut interactions remains unknown. Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis. Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury. This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury. Our research identified three key points. First, the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury. Second, following spinal cord injury, weakened intestinal peristalsis, prolonged intestinal transport time, and immune dysfunction of the intestine caused by abnormal autonomic nerve function, as well as frequent antibiotic treatment, may induce gut dysbiosis. Third, the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury; cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system. Fecal microbiota transplantation, probiotics, dietary interventions, and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota. Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.}, }
@article {pmid37714338, year = {2023}, author = {Liu, D and Gao, X and Huang, X and Fan, Y and Wang, YE and Zhang, Y and Chen, X and Wen, J and He, H and Hong, Y and Liang, Y and Zhang, Y and Liu, Z and Chen, S and Li, X}, title = {Moderate altitude exposure impacts host fasting blood glucose and serum metabolome by regulation of the intestinal flora.}, journal = {The Science of the total environment}, volume = {905}, number = {}, pages = {167016}, doi = {10.1016/j.scitotenv.2023.167016}, pmid = {37714338}, issn = {1879-1026}, mesh = {Humans ; Mice ; Animals ; *Gastrointestinal Microbiome ; Blood Glucose ; Propionates ; Glutamic Acid ; Altitude ; Escherichia coli ; Metabolome ; Glucose ; Fasting ; }, abstract = {Moderate altitude exposure has shown beneficial effects on diabetes incidence but the underlying mechanisms are not understood. Our study aimed to investigate how the human gut microbiome impacted the serum metabolome and associated with glucose homeostasis in healthy Chinese individuals upon moderate-altitude exposure. Faecal microbiome composition was assessed using shotgun metagenomic sequencing. Serum metabolome was acquired by untargeted metabolomics technology, and amino acids (AAs) and propionic acid in serum were quantified by targeted metabolomics technology. The results indicated that the moderate-altitude exposed individuals presented lowered fasting blood glucose (FBG) and propionic acid, increased circulating L-Glutamine but decreased L-Glutamate and L-Valine, which correlated with enriched Bacteroidetes and decreased Proteobacteria. Additionally, the silico causality associations among gut microbiota, serum metabolome and host FBG were analyzed by mediation analysis. It showed that increased Bacteroides ovatus (B. ovatus) and decreased Escherichia coli (E. coli) were identified as the main antagonistic species driving the association between L-Glutamate and FBG in silico causality. Furthermore, the high-fat diet (HFD) fed mice subjected to faecal microbiota transplantation (FMT) were applied to validate the cause-in-fact effects of gut microbiota on the beneficial glucose response. We found that microbiome in the moderate-altitude exposed donor could predict the extent of the FBG response in recipient mice, which showed lowered FBG, L-Glutamate and Firmicutes/Bacteroidetes ratio. Our findings suggest that moderate-altitude exposure targeting gut microbiota and circulating metabolome, may pave novel avenues to counter dysglycemia.}, }
@article {pmid37712213, year = {2023}, author = {Mahroum, N and Seida, R and Shoenfeld, Y}, title = {Triggers and regulation: the gut microbiome in rheumatoid arthritis.}, journal = {Expert review of clinical immunology}, volume = {19}, number = {12}, pages = {1449-1456}, doi = {10.1080/1744666X.2023.2260103}, pmid = {37712213}, issn = {1744-8409}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; *Arthritis, Rheumatoid/drug therapy ; *Microbiota ; Inflammation/complications ; }, abstract = {INTRODUCTION: Rheumatoid arthritis is a chronic inflammatory disease marked by systemic symptoms and joint degeneration. Interestingly, the development and progression of rheumatoid arthritis have been linked to the microbiome, notably the gut microbiome. Dysbiosis, an alteration in the gut microbiome, has been connected to the etiology and pathogenesis of rheumatoid arthritis. For instance, dysbiosis increases intestinal permeability and promotes the movement of bacteria and their products, which in turn triggers and aggravates systemic inflammation.<br><br>AREAS COVERED: The correlation between the gut microbiome and RA. Triggers of RA including dysbiosis. The therapeutic potential of the gut microbiome in RA due to its critical function in influencing the immune response. The fecal microbiota transplantation (FMT), a therapeutic strategy that involves the transfer of healthy fecal microbiota from a donor to a recipient, has produced encouraging results in the treatment of several autoimmune illnesses, including rheumatoid arthritis.<br><br>EXPERT OPINION: The role of the gut microbiome in RA is critical and serves as a basis for etiology and pathogenesis, as well as having therapeutic implications. In our opinion, FMT is an excellent example of this correlation. Still, more investigations and well-designed studies are needed in order to make firm conclusions and recommendations.}, }
@article {pmid37712178, year = {2023}, author = {Sfanos, KS}, title = {Intratumoral Bacteria as Mediators of Cancer Immunotherapy Response.}, journal = {Cancer research}, volume = {83}, number = {18}, pages = {2985-2986}, doi = {10.1158/0008-5472.CAN-23-1857}, pmid = {37712178}, issn = {1538-7445}, mesh = {Humans ; Animals ; Mice ; *Esophageal Squamous Cell Carcinoma ; *Esophageal Neoplasms/therapy ; Immunotherapy ; *Microbiota ; Bacteria ; Tumor Microenvironment ; }, abstract = {Multiple lines of evidence spanning from animal models to human clinical trials indicate that the microbiome influences cancer immunotherapy response. Whereas initial studies focused exclusively on the gastrointestinal (gut) microbiota-tumor axis, more recent studies have examined the possibility that bacteria located within tumor cells or within the tumor microenvironment mediate cancer treatment response. Strikingly, this phenomenon has been demonstrated in cancers that arise in anatomic locations that are traditionally thought to be devoid of resident microbiota. In this issue of Cancer Research, Wu and colleagues examine the effects of intratumoral bacterial signatures on treatment response in the setting of neoadjuvant chemotherapy combined with immunotherapy (NACI) in the treatment of esophageal squamous cell carcinoma (ESCC). The study reports that intratumoral Streptococcus, presumably due to bacterial translocation from the gut, predicts the treatment efficacy of NACI in murine models as well as individuals with ESCC. These new findings further highlight the possibility that the presence of intratumoral microbes as well as their associated metabolites influence both the tumor immune microenvironment and immunotherapy efficacy. These findings also raise the intriguing possibility of cross-reactivity between tumor and bacterial antigens. Given that the gut microbiome is potentially a modifiable factor via diet, prebiotics/probiotics, and fecal microbiota transplantation, among other strategies, further exploration into the mechanisms by which gut and/or intratumoral bacteria influence antitumor immunity is certainly warranted. See related article by Wu et al., p. 3131.}, }
@article {pmid37712110, year = {2023}, author = {Liao, Y and Peng, Z and Xu, S and Meng, Z and Li, D and Zhou, X and Zhang, R and Shi, S and Hao, L and Liu, L and Yang, W}, title = {Deoxynivalenol Exposure Induced Colon Damage in Mice Independent of the Gut Microbiota.}, journal = {Molecular nutrition &amp; food research}, volume = {67}, number = {22}, pages = {e2300317}, doi = {10.1002/mnfr.202300317}, pmid = {37712110}, issn = {1613-4133}, support = {2022YFC3600600//National Key Research and Development Program of China/ ; NSFC82173521//National Natural Science Foundation of China/ ; 2018YFC1603100//National Natural Science Foundation of China/ ; AT2021-01//Hubei Provincial Key Laboratory for Applied Toxicology/ ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Colon ; Tight Junction Proteins ; Anti-Bacterial Agents ; }, abstract = {SCOPE: To investigate whether deoxynivalenol (DON) can induce intestinal damage through gut microbiota in mice.<br><br>METHODS AND RESULTS: Mice are orally administered DON (1 mg&#xa0;kg[-1] bw&#xa0;day[-1]) for 4 weeks, and then recipient mice receive fecal microbiota transplantation (FMT) from DON-exposed mice after antibiotic treatment. Furthermore, the mice are orally treated with DON (1 mg kg[-1] bw&#xa0;day[-1]) for 4 weeks after antibiotic treatment. Histological damage, disruption of tight junction protein expression, and increased oxidative stress and apoptosis in the colon as well as higher serum lipopolysaccharides are observed after DON exposure. Moreover, DON exposure changes the composition and diversity of the gut microbiota as well as the contents of fecal metabolites (mainly bile acids). Differential metabolic pathways may be related to mitochondrial metabolism, apoptosis, and inflammation following DON exposure. However, only a decrease in mRNA levels of occludin and claudin-3 is observed in the colon of recipient mice after FMT. After depleting the gut microbiota in mice, DON exposure can also cause histological damage, disorders of tight junction protein expression, and increased oxidative stress and apoptosis in the colon.<br><br>CONCLUSIONS: DON exposure can induce colon damage in mice independent of the gut microbiota.}, }
@article {pmid37709342, year = {2023}, author = {Fenneman, AC and Rampanelli, E and van der Spek, AH and Fliers, E and Nieuwdorp, M}, title = {Protocol for a double-blinded randomised controlled trial to assess the effect of faecal microbiota transplantations on thyroid reserve in patients with subclinical autoimmune hypothyroidism in the Netherlands: the IMITHOT trial.}, journal = {BMJ open}, volume = {13}, number = {9}, pages = {e073971}, pmid = {37709342}, issn = {2044-6055}, mesh = {Fecal Microbiota Transplantation ; *Autoimmune Diseases ; Hashimoto Disease ; Netherlands ; Randomized Controlled Trials as Topic ; Thyroiditis, Autoimmune ; Humans ; *Hypothyroidism/therapy ; }, abstract = {BACKGROUND: Hashimoto's thyroiditis (HT) is a common endocrine autoimmune disease affecting roughly 5% of the general population and involves life-long treatment with levothyroxine, as no curative treatment yet exists. Over the past decade, the crosstalk between gut microbiota and the host immune system has been well-recognised, identifying the gut microbiome as an important factor in host health and disease, including susceptibility to autoimmune diseases. Previous observational studies yielded a link between disruption of the gut microbiome composition and HT. This is the first study that investigates the potential of restoring a disrupted gut microbiome with faecal microbiota transplantations (FMTs) to halt disease progression and dampen autoimmunity.<br><br>METHODS AND ANALYSIS: The IMITHOT trial is a randomised, double-blinded, placebo-controlled study evaluating either autologous or allogenic FMTs in medication-na&#xef;ve patients with subclinical autoimmune hypothyroidism. In total, 34 patients will be enrolled to receive either three allogenic or autologous FMTs. FMT will be made of fresh stool and directly administered into the duodenum. Patients will be evaluated at baseline before the first FMT is administered and at 6, 12 and 24 months post-intervention to assess efficacy and adverse events. The primary outcome measure will be the net incremental increase (incremental area under the curve) on thyrotropin-stimulated free thyroxine and free triiodothyronine release at 6 and 12 months compared with baseline. Results will be disseminated via peer-reviewed journals and international conferences. The recruitment of the first patient and donor occurred on 18 December 2019.<br><br>ETHICS AND DISSEMINATION: Ethics approval was obtained from the hospital Ethics Committee (Medical Ethics Committee) at Amsterdam University Medical Center. The trial's outcomes offer high-quality evidence that aids in unveiling distinct patterns within the gut microbiota potentially associated with improved thyroid function. Consequently, this may open avenues for the future clinical applications of microbial-targeted therapy in individuals at risk of developing overt HT.<br><br>TRIAL REGISTRATION NUMBER: NL7931.}, }
@article {pmid37709134, year = {2023}, author = {Watanabe, Y and Fujisaka, S and Morinaga, Y and Watanabe, S and Nawaz, A and Hatta, H and Kado, T and Nishimura, A and Bilal, M and Aslam, MR and Honda, K and Nakagawa, Y and Softic, S and Hirabayashi, K and Nakagawa, T and Nagai, Y and Tobe, K}, title = {Isoxanthohumol improves obesity and glucose metabolism via inhibiting intestinal lipid absorption with a bloom of Akkermansia muciniphila in mice.}, journal = {Molecular metabolism}, volume = {77}, number = {}, pages = {101797}, pmid = {37709134}, issn = {2212-8778}, mesh = {Glucose/metabolism ; Akkermansia ; Obesity/drug therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; Dietary Fats ; *Insulin Resistance ; Lipase ; Diet, High-Fat/adverse effects ; Verrucomicrobia/genetics/metabolism ; Mice ; Animals ; }, abstract = {OBJECTIVE: Polyphenols have health-promoting effects, such as improving insulin resistance. Isoxanthohumol (IX), a prenylated flavonoid found in beer hops, has been suggested to reduce obesity and insulin resistance; however, the mechanism remains unknown.<br><br>METHODS: High-fat diet-fed mice were administered IX. We analyzed glucose metabolism, gene expression profiles and histology of liver, epididymal adipose tissue and colon. Lipase activity, fecal lipid profiles and plasma metabolomic analysis were assessed. Fecal 16s rRNA sequencing was obtained and selected bacterial species were used for in&#xa0;vitro studies. Fecal microbiota transplantation and monocolonization were conducted to antibiotic-treated or germ-free (GF) mice.<br><br>RESULTS: The administration of IX lowered weight gain, decreased steatohepatitis and improved glucose metabolism. Mechanistically, IX inhibited pancreatic lipase activity and lipid absorption by decreasing the expression of the fatty acid transporter CD36 in the small intestine, which was confirmed by increased lipid excretion in feces. IX administration increased markers of intestinal barrier function, including thickening the mucin layer and increasing caludin-1, a tight-junction related protein in the colon. In contrast, the effects of IX were nullified by antibiotics. As revealed using 16S rRNA sequencing, the microbial community structure changed with a significant increase in the abundance of Akkermansia muciniphila in the IX-treated group. An anaerobic chamber study showed that IX selectively promoted the growth of A.&#xa0;muciniphila while exhibiting antimicrobial activity against some Bacteroides and Clostridium species. To further explore the direct effect of A.&#xa0;muciniphila on lipid and glucose metabolism, we monocolonized either A.&#xa0;muciniphila or Bacteroides thetaiotaomicron to GF mice. A.&#xa0;muciniphila monocolonization decreased CD36 expression in the jejunum and improved glucose metabolism, with decreased levels of multiple classes of fatty acids determined using plasma metabolomic analysis.<br><br>CONCLUSIONS: Our study demonstrated that IX prevents obesity and enhances glucose metabolism by inhibiting dietary fat absorption. This mechanism is linked to suppressing pancreatic lipase activity and shifts in microbial composition, notably an increase in A.&#xa0;muciniphila. These highlight new treatment strategies for preventing metabolic syndrome by boosting the gut microbiota with food components.}, }
@article {pmid37706187, year = {2023}, author = {Gawey, BJ and Khanna, S}, title = {Clostridioides difficile Infection: Landscape and Microbiome Therapeutics.}, journal = {Gastroenterology &amp; hepatology}, volume = {19}, number = {6}, pages = {319-328}, pmid = {37706187}, issn = {1554-7914}, abstract = {Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhea and is common in the community. Both younger individuals who may be healthy otherwise and older individuals with comorbid conditions are at risk for developing CDI, with the predominant risk factor being antibiotic use. Unlike other gastrointestinal infections, CDI is not self-limited, requires antimicrobial therapy, and tends to recur at high rates even without additional risk factor exposure. The goals of CDI management include controlling active symptoms and using a recurrence prevention strategy such as a narrow-spectrum antibiotic, tapered and pulsed regimens, antibody- based therapies (directed against toxin B), or microbiome restoration. In recent years, fecal microbiota transplantation (FMT) has been the most used modality to prevent recurrent CDI with high cure rates. Heterogeneity, lack of scalability, and serious adverse events from FMT have led to development of standardized microbiota restoration therapies (MRTs). The US Food and Drug Administration has approved 2 stool-derived MRTs for prevention of recurrent CDI: fecal microbiota, live-jslm, an enema-based therapy; and fecal microbiota spores, live-brpk, an oral therapy. A phase 3 trial for a synthetic oral MRT is underway. This article outlines the pathophysiology and treatment of CDI, focusing primarily on the gut microbiome and standardized MRTs.}, }
@article {pmid37704493, year = {2023}, author = {Guillot, N and Roméo, B and Manesh, SS and Milano, G and Brest, P and Zitvogel, L and Hofman, P and Mograbi, B}, title = {Manipulating the gut and tumor microbiota for immune checkpoint inhibitor therapy: from dream to reality.}, journal = {Trends in molecular medicine}, volume = {29}, number = {11}, pages = {897-911}, doi = {10.1016/j.molmed.2023.08.004}, pmid = {37704493}, issn = {1471-499X}, mesh = {Humans ; Animals ; Mice ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Immunotherapy ; *Neoplasms/drug therapy/etiology ; *Microbiota ; Tumor Microenvironment ; }, abstract = {The past decade has witnessed a revolution in cancer treatment by shifting from conventional therapies to immune checkpoint inhibitors (ICIs). These immunotherapies unleash the host immune system against the tumor and have achieved unprecedented durable remission. However, 80% of patients do not respond. This review discusses how bacteria are unexpected drivers that reprogram tumor immunity. Manipulating the microbiota impacts on tumor development and reprograms the tumor microenvironment (TME) of mice on immunotherapy. We anticipate that harnessing commensals and the tumor microbiome holds promise to identify patients who will benefit from immunotherapy and guide the choice of new ICI combinations to advance treatment efficacy.}, }
@article {pmid37704113, year = {2023}, author = {Gou, H and Su, H and Liu, D and Wong, CC and Shang, H and Fang, Y and Zeng, X and Chen, H and Li, Y and Huang, Z and Fan, M and Wei, C and Wang, X and Zhang, X and Li, X and Yu, J}, title = {Traditional Medicine Pien Tze Huang Suppresses Colorectal Tumorigenesis Through Restoring Gut Microbiota and Metabolites.}, journal = {Gastroenterology}, volume = {165}, number = {6}, pages = {1404-1419}, doi = {10.1053/j.gastro.2023.08.052}, pmid = {37704113}, issn = {1528-0012}, mesh = {Mice ; Animals ; Signal Transduction ; *Gastrointestinal Microbiome ; Dextran Sulfate/toxicity ; Phosphatidylinositol 3-Kinases/metabolism ; Apoptosis ; Medicine, Traditional ; *Colorectal Neoplasms/chemically induced/prevention &amp; control/metabolism ; Carcinogenesis ; Azoxymethane/toxicity ; }, abstract = {BACKGROUND &amp; AIMS: Pien Tze Huang (PZH) is a well-established traditional medicine with beneficial effects against inflammation and cancer. We aimed to explore the chemopreventive effect of PZH in colorectal cancer (CRC) through modulating gut microbiota.<br><br>METHODS: CRC mouse models were established by azoxymethane plus dextran sulfate sodium treatment or in Apc[min/+] mice treated with or without PZH (270 mg/kg and 540 mg/kg). Gut barrier function was determined by means of intestinal permeability assays and transmission electron microscopy. Fecal microbiota and metabolites were analyzed by means of metagenomic sequencing and liquid chromatography mass spectrometry, respectively. Germ-free mice or antibiotic-treated mice were used as models of microbiota depletion.<br><br>RESULTS: PZH inhibited colorectal tumorigenesis in azoxymethane plus dextran sulfate sodium-treated mice and in Apc[min/+] mice in a dose-dependent manner. PZH treatment altered the gut microbiota profile, with an increased abundance of probiotics Pseudobutyrivibrio xylanivorans and Eubacterium limosum, while pathogenic bacteria Aeromonas veronii, Campylobacter jejuni, Collinsella aerofaciens, and Peptoniphilus harei were depleted. In addition, PZH increased beneficial metabolites taurine and hypotaurine, bile acids, and unsaturated fatty acids, and significantly restored gut barrier function. Transcriptomic profiling revealed that PZH inhibited PI3K-Akt, interleukin-17, tumor&#xa0;necrosis factor, and cytokine-chemokine signaling. Notably, the chemopreventive effect of PZH involved both microbiota-dependent and -independent mechanisms. Fecal microbiota transplantation from PZH-treated mice to germ-free mice partly recapitulated the chemopreventive effects of PZH. PZH components ginsenoside-F2 and ginsenoside-Re demonstrated inhibitory effects on CRC cells and primary organoids, and PZH also inhibited tumorigenesis in azoxymethane plus dextran sulfate sodium-treated germ-free mice.<br><br>CONCLUSIONS: PZH manipulated gut microbiota and metabolites toward a more favorable profile, improved gut barrier function, and suppressed oncogenic and pro-inflammatory pathways, thereby suppressing colorectal carcinogenesis.}, }
@article {pmid37703304, year = {2023}, author = {Subramaniam, S and Fares-Gusmao, R and Sato, S and Cullen, JM and Takeda, K and Farci, P and McGivern, DR}, title = {Distinct disease features of acute and persistent genotype 3 hepatitis E virus infection in immunocompetent and immunosuppressed Mongolian gerbils.}, journal = {PLoS pathogens}, volume = {19}, number = {9}, pages = {e1011664}, pmid = {37703304}, issn = {1553-7374}, mesh = {Animals ; Humans ; *Hepatitis E virus/genetics ; Gerbillinae ; Tacrolimus ; Viremia ; *Hepatitis E ; Genotype ; }, abstract = {Hepatitis E virus (HEV) causes self-limited acute hepatitis in immunocompetent individuals and can establish chronic infection in solid organ transplant recipients taking immunosuppressive drugs. A well characterized small animal model is needed to understand HEV pathogenesis. In this study, we established a robust model to study acute and persistent HEV infection using Mongolian gerbils (Meriones unguiculatus) with or without immunosuppression. Gerbils were implanted subcutaneously with continuous release tacrolimus pellet to induce immunosuppression. Gerbils with or without tacrolimus treatment were inoculated with HEV intraperitoneally. Viremia, fecal virus shedding, serum antibody and ALT levels, liver histopathological lesions, hepatocyte apoptosis, and liver macrophage distribution were assessed. Mild to moderate self-limited hepatitis and IgM and IgG antibody responses against HEV ORF2 were observed in immunocompetent gerbils. Levels of HEV-specific IgM responses were higher and lasted longer in immunocompetent gerbils with higher peak viremia. Persistent viremia and fecal virus shedding with either weak, or absent HEV antibody levels were seen in immunosuppressed gerbils. Following HEV infection, serum ALT levels were increased, with lower and delayed peaks observed in immunosuppressed compared to immunocompetent gerbils. In immunocompetent gerbils, foci of apoptotic hepatocytes were detected that were distributed with inflammatory infiltrates containing CD68+ macrophages. However, these foci were absent in immunosuppressed gerbils. The immunosuppressed gerbils showed no inflammation with no increase in CD68+ macrophages despite high virus replication in liver. Our findings suggest adaptive immune responses are necessary for inducing hepatocyte apoptosis, CD68+ macrophage recruitment, and inflammatory cell infiltration in response to HEV infection. Our studies show that Mongolian gerbils provide a promising model to study pathogenesis during acute and persistent HEV infection.}, }
@article {pmid37702234, year = {2024}, author = {Sepordeh, S and Jafari, AM and Bazzaz, S and Abbasi, A and Aslani, R and Houshmandi, S and Rad, AH}, title = {Postbiotic as Novel Alternative Agent or Adjuvant for the Common Antibiotic Utilized in the Food Industry.}, journal = {Current pharmaceutical biotechnology}, volume = {25}, number = {10}, pages = {1245-1263}, pmid = {37702234}, issn = {1873-4316}, support = {68571//Student Research Committee, Tabriz University of Medical Sciences/ ; }, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology/administration &amp; dosage ; *Probiotics/therapeutic use/administration &amp; dosage ; Animals ; Food Industry ; Gastrointestinal Microbiome/drug effects ; Drug Resistance, Microbial ; Drug Resistance, Bacterial ; }, abstract = {BACKGROUND: Antibiotic resistance is a serious public health problem as it causes previously manageable diseases to become deadly infections that can cause serious disability or even death. Scientists are creating novel approaches and procedures that are essential for the treatment of infections and limiting the improper use of antibiotics in an effort to counter this rising risk.<br><br>OBJECTIVES: With a focus on the numerous postbiotic metabolites formed from the beneficial gut microorganisms, their potential antimicrobial actions, and recent associated advancements in the food and medical areas, this review presents an overview of the emerging ways to prevent antibiotic resistance.<br><br>RESULTS: Presently, scientific literature confirms that plant-derived antimicrobials, RNA therapy, fecal microbiota transplantation, vaccines, nanoantibiotics, haemofiltration, predatory bacteria, immunotherapeutics, quorum-sensing inhibitors, phage therapies, and probiotics can be considered natural and efficient antibiotic alternative candidates. The investigations on appropriate probiotic strains have led to the characterization of specific metabolic byproducts of probiotics named postbiotics. Based on preclinical and clinical studies, postbiotics with their unique characteristics in terms of clinical (safe origin, without the potential spread of antibiotic resistance genes, unique and multiple antimicrobial action mechanisms), technological (stability and feasibility of largescale production), and economic (low production costs) aspects can be used as a novel alternative agent or adjuvant for the common antibiotics utilized in the production of animal-based foods.<br><br>CONCLUSION: Postbiotic constituents may be a new approach for utilization in the pharmaceutical and food sectors for developing therapeutic treatments. Further metabolomics investigations are required to describe novel postbiotics and clinical trials are also required to define the sufficient dose and optimum administration frequency of postbiotics.}, }
@article {pmid37701737, year = {2023}, author = {Yuan, Q and Sun, L and Ma, G and Shen, H and Wang, S and Guo, F and Sun, X and Gao, C}, title = {Alterations of the gut microbial community structure modulates the Th17 cells response in a rat model of asphyxial cardiac arrest.}, journal = {Biochemistry and biophysics reports}, volume = {35}, number = {}, pages = {101543}, pmid = {37701737}, issn = {2405-5808}, abstract = {Th17 cells triggered inflammation is a critical element in cerebral ischemic injury, and the gut microbiota intricately impacts T lymphocytes. Nevertheless, it remains unclear whether the gut microbiota involves in cardiac arrest/cardiopulmonary resuscitation (CA/CPR) induced-brain injury through Th17 cells. The present study investigated the interaction between gut microbiota and Th17 cells in a rat model. We observed that CA/CPR induced the alterations of the gut microbial community structure, and elevated the level of IL-17 in the serum, and a slight infiltration of Th17 cells into the brain. The Th17 cells were increased significantly in the peripheral blood, 28.33 ± 6.18% of these Th17 cells were derived from the Peyer's patches of small intestine. Furthermore, fecal microbiota transplantation (FMT) from rats with CA/CPR induced Th17 cell response, promoting hippocampal cell apoptosis and declining learning ability and memory in recipient rats. Taken together, CA/CPR-induced alterations of the gut microbial community structure stimulated Th17 cell response which aggravated brain injury.}, }
@article {pmid37699894, year = {2023}, author = {Wortelboer, K and de Jonge, PA and Scheithauer, TPM and Attaye, I and Kemper, EM and Nieuwdorp, M and Herrema, H}, title = {Phage-microbe dynamics after sterile faecal filtrate transplantation in individuals with metabolic syndrome: a double-blind, randomised, placebo-controlled clinical trial assessing efficacy and safety.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5600}, pmid = {37699894}, issn = {2041-1723}, mesh = {Bacteriophages ; Blood Glucose ; Double-Blind Method ; *Metabolic Syndrome/therapy ; Humans ; *Fecal Microbiota Transplantation ; }, abstract = {Bacteriophages (phages) are bacterial viruses that have been shown to shape microbial communities. Previous studies have shown that faecal virome transplantation can decrease weight gain and normalize blood glucose tolerance in diet-induced obese mice. Therefore, we performed a double-blind, randomised, placebo-controlled pilot study in which 24 individuals with metabolic syndrome were randomised to a faecal filtrate transplantation (FFT) from a lean healthy donor (n = 12) or placebo (n = 12). The primary outcome, change in glucose metabolism, and secondary outcomes, safety and longitudinal changes within the intestinal bacteriome and phageome, were assessed from baseline up to 28 days. All 24 included subjects completed the study and are included in the analyses. While the overall changes in glucose metabolism are not significantly different between both groups, the FFT is well-tolerated and without any serious adverse events. The phage virion composition is significantly altered two days after FFT as compared to placebo, which coincides with more virulent phage-microbe interactions. In conclusion, we provide evidence that gut phages can be safely administered to transiently alter the gut microbiota of recipients.}, }
@article {pmid37698033, year = {2023}, author = {Zuo, T and Liang, G and Huang, Z and Cao, Z and Bai, F and Zhou, Y and Wu, X and Wu, X and Chen, YQ and Balati, M and Maimaitiyiming, M and ,  and Lan, P}, title = {Baseline gut microbiome features prior to SARS-CoV-2 infection are associated with host symptoms in and post COVID-19.}, journal = {Journal of medical virology}, volume = {95}, number = {9}, pages = {e29083}, doi = {10.1002/jmv.29083}, pmid = {37698033}, issn = {1096-9071}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19 ; SARS-CoV-2 ; *Microbiota ; China/epidemiology ; }, abstract = {The human gut microbiome varies substantially across individuals and populations and differentially tames our immunity at steady-state. Hence, we hypothesize that the large heterogeneity of gut microbiomes at steady-state may shape our baseline immunity differentially, and then mediate discrepant immune responses and symptoms when one encounters a viral infection, such as SARS-CoV-2 infection. To validate this hypothesis, we conducted an exploratory, longitudinal microbiome-COVID-19 study involving homogenous young participants from two geographically different regions in China. Subjects were recruited and sampled of fecal specimens before the 3-week surge window of COVID-19 (between December 11 and December 31, 2022) in China, and then were followed up for assessment of COVID-19 and post-COVID-19 manifestations. Our data showed that the baseline gut microbiome composition was intricately associated with different COVID-19 manifestations, particularly gastrointestinal involvement and post-COVID-19 lingering symptoms, in both an individual- and population-dependent manner. Our study intriguingly for the first time highlight that the gut microbiome at steady-state may prepare us differentially for weathering a respiratory viral infection.}, }
@article {pmid37697393, year = {2023}, author = {Zeng, X and Li, J and Shan, W and Lai, Z and Zuo, Z}, title = {Gut microbiota of old mice worsens neurological outcome after brain ischemia via increased valeric acid and IL-17 in the blood.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {204}, pmid = {37697393}, issn = {2049-2618}, support = {R01 NS099118/NS/NINDS NIH HHS/United States ; RF1 AG061047/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Male ; Mice ; *Brain Ischemia ; Fatty Acids, Nonesterified ; *Gastrointestinal Microbiome ; Inflammation ; Interleukin-17 ; Mice, Inbred C57BL ; *Aging ; }, abstract = {BACKGROUND: Aging is a significant risk factor for ischemic stroke and worsens its outcome. However, the mechanisms for this worsened neurological outcome with aging are not clearly defined.<br><br>RESULTS: Old C57BL/6J male mice (18 to 20 months old) had a poorer neurological outcome and more severe inflammation after transient focal brain ischemia than 8-week-old C57BL/6J male mice (young mice). Young mice with transplantation of old mouse gut microbiota had a worse neurological outcome, poorer survival curve, and more severe inflammation than young mice receiving young mouse gut microbiota transplantation. Old mice and young mice transplanted with old mouse gut microbiota had an increased level of blood valeric acid. Valeric acid worsened neurological outcome and heightened inflammatory response including blood interleukin-17 levels after brain ischemia. The increase of interleukin-17 caused by valeric acid was inhibited by a free fatty acid receptor 2 antagonist. Neutralizing interleukin-17 in the blood by its antibody improved neurological outcome and attenuated inflammatory response in mice with brain ischemia and receiving valeric acid. Old mice transplanted with young mouse feces had less body weight loss and better survival curve after brain ischemia than old mice transplanted with old mouse feces or old mice without fecal transplantation.<br><br>CONCLUSIONS: These results suggest that the gut microbiota-valeric acid-interleukin-17 pathway contributes to the aging-related changes in the outcome after focal brain ischemia and response to stimulus. Valeric acid may activate free fatty acid receptor 2 to increase interleukin-17.}, }
@article {pmid37696680, year = {2024}, author = {Del Chierico, F and Cardile, S and Baldelli, V and Alterio, T and Reddel, S and Bramuzzo, M and Knafelz, D and Lega, S and Bracci, F and Torre, G and Maggiore, G and Putignani, L}, title = {Characterization of the Gut Microbiota and Mycobiota in Italian Pediatric Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {30}, number = {4}, pages = {529-537}, pmid = {37696680}, issn = {1536-4844}, support = {//Italian Ministry of Health/ ; }, mesh = {Humans ; Child ; *Colitis, Ulcerative/complications ; *Gastrointestinal Microbiome ; *Cholangitis, Sclerosing/complications ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; Bacteroidetes ; Italy ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory, cholestatic liver disease of unknown etiopathogenesis, often associated with inflammatory bowel diseases. Recent evidence ascribes, together with immunologic and environmental components, a significant role to the intestinal microbiota or its molecules in the PSC pathogenesis.<br><br>METHODS: By metagenomic sequencing of 16S rRNA and ITS2 loci, we describe the fecal microbiota and mycobiota of 26 pediatric patients affected by PSC and concomitant ulcerative colitis (PSC-UC), 27 patients without PSC but with UC (UC), and 26 healthy subjects (CTRLs).<br><br>RESULTS: Compared with CTRL, the bacterial and fungal gut dysbiosis was evident for both PSC-UC and UC groups; in particular, Streptococcus, Saccharomyces, Sporobolomyces, Tilletiopsis, and Debaryomyces appeared increased in PSC-UC, whereas Klebsiella, Haemophilus, Enterococcus Collinsella, Piptoporus, Candida, and Hyphodontia in UC. In both patient groups, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma and Malassezia were decreased. Co-occurrence analysis evidenced the lowest number of nodes and edges for fungi networks compared with bacteria. Finally, we identified a specific patient profile, based on liver function tests, bacterial and fungal signatures, that is able to distinguish PSC-UC from UC patients.<br><br>CONCLUSIONS: We describe the gut microbiota and mycobiota dysbiosis associated to PSC-UC disease. Our results evidenced a gut imbalance, with the reduction of gut commensal microorganisms with stated anti-inflammatory properties (ie, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma, and Malassezia) and the increase of pathobionts (ie, Streptococcus, Saccharomyces, and Debaryomyces) that could be involved in PSC progression. Altogether, these events may concur in the pathophysiology of PSC in the framework of UC.}, }
@article {pmid37696191, year = {2023}, author = {Gao, T and Zhang, H and Li, Q and Zhao, F and Wang, N and He, W and Zhang, J and Wang, R}, title = {Fuzi decoction treats chronic heart failure by regulating the gut microbiota, increasing the short-chain fatty acid levels and improving metabolic disorders.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {236}, number = {}, pages = {115693}, doi = {10.1016/j.jpba.2023.115693}, pmid = {37696191}, issn = {1873-264X}, abstract = {Fuzi decoction (FZD) is clinically used to treat chronic heart failure (CHF) in China, but the mechanism underlying FZD treatment in CHF remains unclear. Here, we investigated the potential mechanism underlying FZD treatment of CHF in rats. First, the compounds in FZD-containing serum of rats were identified, and 16 S rRNA sequencing and GC-MS-based untargeted metabolomics analysis were then performed. The levels of fecal short-chain fatty acids (SCFAs) were determined and compared, and fecal microbiota transplantation (FMT) was used to verify the role of the gut microbiota. Our results identified 27 in FD-containing serum. FZD increased the Firmicutes-to-Bacteroidetes ratio and the Lactobacillus abundance and affected the β diversity of the gut microbiota in rats with CHF. Differential species analysis showed that Lactobacillus and Prevotella were biomarkers of FZD treatment of CHF. Untargeted metabolomics analysis revealed that FZD affected valine, leucine and isoleucine biosynthesis; galactose metabolism; and aminoacyl-tRNA biosynthesis in rats with CHF. Furthermore, FZD significantly increased the acetic acid, propionic acid, butyric acid and isopentanoic acid levels in the feces of rats with CHF. Correlation analysis showed that the butyric acid and Lactobacillus levels had the strongest correlation in the control, sham and high-dose FZD (HFZD) groups, and many microbiota components were closely related to differentially abundant metabolites. FMT revealed that the fecal microbiota obtained from the HFZD group changed the heart rate; the brain natriuretic peptide (BNP), acetic acid, propionic acid, butyric acid, and metabolite levels; and the gut microbiota in rats with CHF. In summary, our study revealed that the mechanism of action of FZD in CHF treatment may be related to improvements in the gut microbiota, elevations in the SCFA content and the regulation of valine, leucine, and isoleucine biosynthesis; galactose metabolism; and other metabolic pathways.}, }
@article {pmid37694136, year = {2023}, author = {Bubeck, AM and Urbain, P and Horn, C and Jung, AS and Ferrari, L and Ruple, HK and Podlesny, D and Zorn, S and Laupsa-Borge, J and Jensen, C and Lindseth, I and Lied, GA and Dierkes, J and Mellgren, G and Bertz, H and Matysik, S and Krautbauer, S and Liebisch, G and Schoett, HF and Dankel, SN and Fricke, WF}, title = {High-fat diet impact on intestinal cholesterol conversion by the microbiota and serum cholesterol levels.}, journal = {iScience}, volume = {26}, number = {9}, pages = {107697}, pmid = {37694136}, issn = {2589-0042}, abstract = {Cholesterol-to-coprostanol conversion by the intestinal microbiota has been suggested to reduce intestinal and serum cholesterol availability, but the relationship between intestinal cholesterol conversion and the gut microbiota, dietary habits, and serum lipids has not been characterized in detail. We measured conserved proportions of cholesterol high and low-converter types in individuals with and without obesity from two distinct, independent low-carbohydrate high-fat (LCHF) dietary intervention studies. Across both cohorts, cholesterol conversion increased in previous low-converters after LCHF diet and was positively correlated with the fecal relative abundance of Eubacterium coprostanoligenes. Lean cholesterol high-converters had increased serum triacylglycerides and decreased HDL-C levels before LCHF diet and responded to the intervention with increased LDL-C, independently of fat, cholesterol, and saturated fatty acid intake. Our findings identify the cholesterol high-converter type as a microbiome marker, which in metabolically healthy lean individuals is associated with increased LDL-C in response to LCHF.}, }
@article {pmid37692169, year = {2023}, author = {Negi, S and Pahari, S}, title = {Editorial: Gut microbiota as a weapon against infections.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1277517}, doi = {10.3389/fcimb.2023.1277517}, pmid = {37692169}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; *Infections ; }, }
@article {pmid37691890, year = {2023}, author = {Wang, B and Hu, W and Zhang, X and Cao, Y and Shao, L and Xu, X and Liu, P}, title = {Sarcopenia and gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {35}, number = {4}, pages = {386-398}, pmid = {37691890}, issn = {1000-9604}, abstract = {OBJECTIVE: The aim of this study was to investigate the prevalence of sarcopenia (SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT).<br><br>METHODS: A total of 108 patients with various hematological disorders were selected from Peking University People's Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity.<br><br>RESULTS: After HSCT, significant decreases in calf circumference and body mass index (BMI) were observed, accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT (P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients (P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the post-HSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre- and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size (LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups (P<0.05).<br><br>CONCLUSIONS: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.}, }
@article {pmid37691753, year = {2023}, author = {Malik, A and Malik, MI}, title = {Fecal Microbiota Transplantation in Human Immunodeficiency Virus-Infected Patient Population: A Systematic Review and Meta-Analysis.}, journal = {Gastroenterology research}, volume = {16}, number = {4}, pages = {209-216}, pmid = {37691753}, issn = {1918-2805}, abstract = {BACKGROUND: Patients with human immunodeficiency virus (HIV) infection suffer from alterations in gut microbiota due to recurrent gastrointestinal infections and systemic inflammation. Fecal microbiota transplantation (FMT) appears to be a potential therapy; however, there are concerns about its safety. Likewise, no previous meta-analysis evaluated FMT efficacy in HIV-infected patients.<br><br>METHODS: We conducted a thorough electronic search on PubMed, Scopus, OVID, Web of Science, and Cochrane CENTRAL for clinical studies assessing the safety and efficacy of FMT in patients with HIV and gastrointestinal dysbiosis, where FMT was indicated to restore the disrupted microbiota.<br><br>RESULTS: FMT significantly restored the typical microbiome in patients with Clostridium difficile (C. difficile) and non-C. difficile and reduced the risk of gastrointestinal infections in HIV patients receiving antiretroviral therapy (odds ratio (OR) = 0.774, 95% confidence interval (CI): (0.62, 0.966)). Furthermore, adverse events, such as distention and bloating, associated with FMT were comparable between HIV and health controls (OR = 0.60, 95% CI: (0.07, 4.6)), with no statistical difference.<br><br>CONCLUSIONS: Current evidence demonstrated that FMT is safe and effective in HIV patients suffering from alterations in gut microbiota. We recommend further multi-centric clinical studies to address the optimal transplant amount and source for FMT. To the best of our knowledge, this is the first meta-analysis to assess the safety and efficacy of FMT in patients with HIV.}, }
@article {pmid37690971, year = {2023}, author = {Liu, X and Liu, M and Zhao, M and Li, P and Gao, C and Fan, X and Cai, G and Lu, Q and Chen, X}, title = {Fecal microbiota transplantation for the management of autoimmune diseases: Potential mechanisms and challenges.}, journal = {Journal of autoimmunity}, volume = {141}, number = {}, pages = {103109}, doi = {10.1016/j.jaut.2023.103109}, pmid = {37690971}, issn = {1095-9157}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Treatment Outcome ; *Autoimmune Diseases/therapy/etiology ; Feces ; }, abstract = {Autoimmune diseases (AIDs) are a series of immune-mediated lethal diseases featured by over-activated immune cells attacking healthy self-tissues and organs due to the loss of immune tolerance, which always causes severe irreversible systematical organ damage and threatens human health heavily. To date, there are still no definitive cures for the treatment of AIDs due to their pathogenesis has not been clearly understood. Besides, the current clinical treatments of AIDs majorly rely on glucocorticoids and immune suppressors, which can lead to serious side effects. In the past years, there are increasing studies demonstrating that an imbalance of gut microbiota is intimately related to the pathogenesis of various AIDs, shedding light on the development of therapeutics by targeting the gut microbiota for the management of AIDs. Among all the approaches targeting the gut microbiota, fecal microbiota transplantation (FMT) has attracted increasing interest, and it has been proposed as a possible strategy to intervene in the homeostasis of gut microbiota for the treatment of various diseases. However, despite the reported good curative effects and clinical studies conducted on FMT, the detailed mechanisms of FMT for the effective treatment of those diseases have not been figured out. To fully understand the mechanisms of the therapeutic effects of FMT on AIDs and improve the therapeutic efficacy of FMT treatment, a systematic review of this topic is necessary. Hence, in this review paper, the potential mechanisms of FMT for the treatment of various AIDs were summarized, including promotion, shaping, activation, or inhibition of the host immune system via the interactions between the microorganisms and the gut immune system, gut-brain, gut-liver, gut-kidney axis, and so on. Then, applications of FMT for the treatment of various AIDs were detailed presented. Finally, the current challenges and potential solutions for the development of FMT formulations and FMT therapeutics were comprehensively discussed.}, }
@article {pmid37690584, year = {2024}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {An updated overview on the relationship between human gut microbiome dysbiosis and psychiatric and psychological disorders.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {128}, number = {}, pages = {110861}, doi = {10.1016/j.pnpbp.2023.110861}, pmid = {37690584}, issn = {1878-4216}, abstract = {There is a lot of evidence establishing that nervous system development is related to the composition and functions of the gut microbiome. In addition, the central nervous system (CNS) controls the imbalance of the intestinal microbiota, constituting a bidirectional communication system. At present, various gut-brain crosstalk routes have been described, including immune, endocrine and neural circuits via the vagal pathway. Several empirical data have associated gut microbiota alterations (dysbiosis) with neuropsychiatric diseases, such as Alzheimer's disease, autism and Parkinson's disease, and with other psychological disorders, like anxiety and depression. Fecal microbiota transplantation (FMT) therapy has shown that the gut microbiota can transfer behavioral features to recipient animals, which provides strong evidence to establish a causal-effect relationship. Interventions, based on prebiotics, probiotics or synbiotics, have demonstrated an important influence of microbiota on neurological disorders by the synthesis of neuroactive compounds that interact with the nervous system and by the regulation of inflammatory and endocrine processes. Further research is needed to demonstrate the influence of gut microbiota dysbiosis on psychiatric and psychological disorders, and how microbiota-based interventions may be used as potential therapeutic tools.}, }
@article {pmid37689184, year = {2023}, author = {Liu, J and Peng, F and Cheng, H and Zhang, D and Zhang, Y and Wang, L and Tang, F and Wang, J and Wan, Y and Wu, J and Zhou, Y and Feng, W and Peng, C}, title = {Chronic cold environment regulates rheumatoid arthritis through modulation of gut microbiota-derived bile acids.}, journal = {The Science of the total environment}, volume = {903}, number = {}, pages = {166837}, doi = {10.1016/j.scitotenv.2023.166837}, pmid = {37689184}, issn = {1879-1026}, abstract = {The pathologies of many diseases are influenced by environmental temperature. As early as the classical Roman age, people believed that exposure to cold weather was bad for rheumatoid arthritis (RA). However, there is no direct evidence supporting this notion, and the molecular mechanisms of the effects of chronic cold exposure on RA remain unknown. Here, in a temperature-conditioned environment, we found that chronic cold exposure aggravates collagen-induced arthritis (CIA) by increasing ankle swelling, bone erosion, and cytokine levels in rats. Furthermore, in chronic cold-exposed CIA rats, gut microbiota dysbiosis was identified, including a decrease in the differential relative abundance of the families Lachnospiraceae and Ruminococcaceae. We also found that an antibiotic cocktail suppressed arthritis severity under cold conditions. Notably, the fecal microbiota transplantation (FMT) results showed that transplantation of cold-adapted microbiota partly recapitulated the microbiota signature in the respective donor rats and phenocopied the cold-induced effects on CIA rats. In addition, cold exposure disturbed bile acid profiles, in particular decreasing gut microbiota-derived taurohyodeoxycholic acid (THDCA) levels. The perturbation of bile acids was also associated with activation of the TGR5-cAMP-PKA axis and NLRP3 inflammasome. Oral THDCA supplementation mitigated the arthritis exacerbation induced by chronic cold exposure. Our findings identify an important role of aberrant gut microbiota-derived bile acids in cold exposure-related RA, highlighting potential opportunities to treat cold-related RA by manipulating the gut microbiota and/or supplementing with THDCA.}, }
@article {pmid37686740, year = {2023}, author = {Chen, J and Deng, LL and Xiao, XL and Long, SY and Deng, Y and Peng, T and Xie, J and Zhang, XY}, title = {An Association between Decreased Small Intestinal RNA Modification and Disturbed Glucagon-like Peptide-1 Secretion under High-Fat Diet Stress.}, journal = {Nutrients}, volume = {15}, number = {17}, pages = {}, pmid = {37686740}, issn = {2072-6643}, support = {23SYSX0098//Project of Science and Technology Ministry of Sichuan Province/ ; 32001078//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Diet, High-Fat/adverse effects ; Glucagon-Like Peptide 1 ; Mice, Obese ; *Gastrointestinal Hormones ; Intestine, Small ; }, abstract = {Unhealthy diets rich in fats and/or sugar are considered as the major external cause of the obesity epidemic, which is often accompanied by a significant decrease in gut hormone glucagon-like peptide-1 (GLP1) levels. Numerous studies have demonstrated notable contributions of the gut microbiota in this process. Nevertheless, the underlying mechanism still needs further investigation. The role of epigenetic modifications in gene expression and metabolism has been well demonstrated, with m6A methylation on RNAs being the most prevalent modification throughout their metabolism. In the present study, we found that the expressions of small intestinal Gcg and Pc3, two key genes regulating GLP1 expression, were significantly downregulated in obese mice, associated with reduced GLP1 level. Immunohistochemistry analysis indicated that a high-fat diet slightly increased the density of enteroendocrine L cells in the small intestine, implying that decreased GLP1 levels were not caused by the changes in L cell intensity. Instead, the small intestinal m6A level as well as the expression of known "writers", mettl3/14 and wtap, were found to be positively correlated with the expression of Gcg and Pc3. Fecal microbiota transplantation with feces from normal and obese mice daily to antibiotic-treated mice revealed that dysbiosis in diet-induced obesity was sufficient to reduce serum GLP1, small intestinal m6A level, and intestinal expressions of Gcg, Pc3, and writer genes (mettl3/14, wtap). However, as the most direct and universal methyl donor, the production of fecal S-adenosylmethionine was neither affected by the different dietary patterns nor their shaped microbiota. These results suggested that microbial modulation of the epitranscriptome may be involved in regulating GLP1 expression, and highlighted epitranscriptomic modifications as an additional level of interaction between diet and individual health.}, }
@article {pmid37686143, year = {2023}, author = {Campagnoli, LIM and Varesi, A and Barbieri, A and Marchesi, N and Pascale, A}, title = {Targeting the Gut-Eye Axis: An Emerging Strategy to Face Ocular Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {17}, pages = {}, pmid = {37686143}, issn = {1422-0067}, mesh = {Humans ; Eye ; Face ; *Glaucoma ; *Macular Degeneration ; *Diabetic Retinopathy ; }, abstract = {The human microbiota refers to a large variety of microorganisms (bacteria, viruses, and fungi) that live in different human body sites, including the gut, oral cavity, skin, and eyes. In particular, the presence of an ocular surface microbiota with a crucial role in maintaining ocular surface homeostasis by preventing colonization from pathogen species has been recently demonstrated. Moreover, recent studies underline a potential association between gut microbiota (GM) and ocular health. In this respect, some evidence supports the existence of a gut-eye axis involved in the pathogenesis of several ocular diseases, including age-related macular degeneration, uveitis, diabetic retinopathy, dry eye, and glaucoma. Therefore, understanding the link between the GM and these ocular disorders might be useful for the development of new therapeutic approaches, such as probiotics, prebiotics, symbiotics, or faecal microbiota transplantation through which the GM could be modulated, thus allowing better management of these diseases.}, }
@article {pmid37686104, year = {2023}, author = {Uceda, S and Echeverry-Alzate, V and Reiriz-Rojas, M and Martínez-Miguel, E and Pérez-Curiel, A and Gómez-Senent, S and Beltrán-Velasco, AI}, title = {Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach-A Comprehensive Narrative Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {17}, pages = {}, pmid = {37686104}, issn = {1422-0067}, mesh = {Humans ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; Metabolome ; }, abstract = {The comprehensive narrative review conducted in this study delves into the mechanisms of communication and action at the molecular level in the human organism. The review addresses the complex mechanism involved in the microbiota-gut-brain axis as well as the implications of alterations in the microbial composition of patients with neurodegenerative diseases. The pathophysiology of neurodegenerative diseases with neuronal loss or death is analyzed, as well as the mechanisms of action of the main metabolites involved in the bidirectional communication through the microbiota-gut-brain axis. In addition, interventions targeting gut microbiota restructuring through fecal microbiota transplantation and the use of psychobiotics-pre- and pro-biotics-are evaluated as an opportunity to reduce the symptomatology associated with neurodegeneration in these pathologies. This review provides valuable information and facilitates a better understanding of the neurobiological mechanisms to be addressed in the treatment of neurodegenerative diseases.}, }
@article {pmid37681235, year = {2023}, author = {Wu, X and Ai, RJ and Xu, J and Wen, Q and Pan, HQ and Zhang, ZH and Ning, W and Fang, Y and Ding, DF and Wang, Q and Han, S and Liu, X and Wu, M and Jia, ZY and Jia, S and Lin, T and Cui, BT and Nie, YZ and Wang, X and Zhang, FM}, title = {Washed microbiota transplantation for Clostridioides difficile infection: A national multicenter real-world study.}, journal = {Journal of digestive diseases}, volume = {24}, number = {10}, pages = {540-549}, doi = {10.1111/1751-2980.13227}, pmid = {37681235}, issn = {1751-2980}, support = {2021YFA0717004//National Key R&amp;D Program of China/ ; 2023-3HIM//Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; 82170563//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Aged ; Treatment Outcome ; Cohort Studies ; *Clostridioides difficile ; Neoplasm Recurrence, Local ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; *Microbiota ; Recurrence ; }, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) has been recommended for the treatment of recurrent Clostridioides difficile infection (CDI). We aimed to evaluate the therapeutic efficacy and safety of washed microbiota transplantation (WMT), a new method of FMT, for CDI across various medical settings.<br><br>METHODS: This multicenter real-world cohort study included CDI patients undergoing WMT. The primary outcome was the clinical cure rate of CDI within 8&#x2009;weeks after WMT. Secondary outcomes included the CDI recurrence rate and reduction in total abdominal symptom score (TASS) during the follow-up period. Adverse events related to WMT were recorded.<br><br>RESULTS: Altogether 90.7% (49/54) of CDI patients achieved clinical cure after treated with WMT. The cure rate was 83.3% for cases with severe and complicated CDI (ScCDI) (n&#x2009;=&#x2009;30) and 100% for non-ScCDI cases (n&#x2009;=&#x2009;24) (P&#x2009;=&#x2009;0.059). No difference was observed in the clinical cure rate between patients with first and recurrent CDI (91.9% vs 88.2%, P&#x2009;=&#x2009;0.645). One week post-WMT, TASS showed a remarkable decrease compared to that at baseline (P&#x2009;<&#x2009;0.001). Totally, 8.2% (4/49) of patients suffered CDI recurrence during the follow-up period. A WHO performance score of 4, age&#x2009;&#x2265;65&#x2009;years, higher TASS score, and higher Charlson comorbidity index score were potential risk factors for efficacy (P&#x2009;=&#x2009;0.018, 0.03, 0.01, 0.034, respectively). Four (3.8%) transient adverse events related to WMT were observed.<br><br>CONCLUSIONS: This study emphasizes the attractive value of WMT for CDI. Early WMT may be recommended for CDI, especially for those in serious condition or with complex comorbidities.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT03895593 (registered on&#xa0;27 March 2019).}, }
@article {pmid37679804, year = {2023}, author = {Zhang, Z and Ye, J and Liu, X and Zhao, W and Zhao, B and Gao, X and Lan, H and Wu, Y and Yang, Y and Cao, P}, title = {Huangqi Guizhi Wuwu decoction alleviates oxaliplatin-induced peripheral neuropathy via the gut-peripheral nerve axis.}, journal = {Chinese medicine}, volume = {18}, number = {1}, pages = {114}, pmid = {37679804}, issn = {1749-8546}, support = {BRA202202//The 333 high-level talents project of Jiangsu Province/ ; }, abstract = {BACKGROUND: Oxaliplatin-induced peripheral neurotoxicity (OIPN) limits the dose of chemotherapy and seriously affects the quality of life. Huangqi Guizhi Wuwu Decoction (HGWD) is a classical Traditional Chinese Medicine (TCM) formula for the prevention of OIPN. However, its specific pharmacological mechanism of action remains unknown. Our study found that HGWD can effectively alleviate chronic OIPN and regulate intestinal flora. Therefore, we explored the mechanism of action of HGWD in alleviating chronic OIPN from the perspective of intestinal flora.<br><br>METHODS: In this study, we established an OIPN model in C57BL/6 mice treated with different concentrations of HGWD. Mechanical pain and cold pain were assessed at certain time points, and samples of mice colon, dorsal root ganglion (DRG), serum, and feces were collected. Associated inflammation levels in the colon and DRG were detected using immunohistochemical techniques; the serum lipopolysaccharide (LPS) levels and associated inflammation were assessed using the appropriate kits; and 16S rRNA sequencing was used to examine the dynamic changes in gut microorganisms. Finally, established fecal microbiota transplantation (FMT) and antibiotic (ABX) pretreatment models were used to validate flora's role in HGWD for chronic OIPN by pain scoring and related pathological analysis.<br><br>RESULTS: HGWD treatment significantly alleviated pain sensitivity in chronic OIPN mice. Pathological results showed that HGWD treatment improved intestinal ZO-1 expression and reduced serum LPS levels and associated inflammatory factors in the colon, serum, and DRG. The 16S rRNA results showed that HGWD restored the composition of the intestinal flora in a time-dependent manner to alleviate OIPN. FMT and ABX experiments demonstrated that HGWD can alleviate chronic OIPN by regulating intestinal flora homeostasis.<br><br>CONCLUSIONS: HGWD prevents chronic OIPN by dynamically regulating intestinal flora homeostasis, thereby ameliorating intestinal barrier damage and reducing serum LPS and relevant inflammatory factor levels in the colon, serum, and DRG.}, }
@article {pmid37679072, year = {2023}, author = {Zhou, Z and Zhang, Y and Liu, M and Jia, W and Cheng, R and Shen, X and He, F}, title = {[Influence of different fecal microbiota transplantation cycles on the recovery of intestinal microbiota in the antibiotic cocktail-pretreated mice].}, journal = {Wei sheng yan jiu = Journal of hygiene research}, volume = {52}, number = {4}, pages = {585-590}, doi = {10.19813/j.cnki.weishengyanjiu.2023.04.011}, pmid = {37679072}, issn = {1000-8020}, mesh = {Animals ; Mice ; Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Feces ; Anti-Bacterial Agents/pharmacology ; }, abstract = {OBJECTIVE: To explore the effects of different transplantation frequencies and time of fecal microbiota transplantation on mice.<br><br>METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, fecal microbiota transplantation group 1(FMT1), fecal microbiota transplantation group 2(FMT2), and fecal microbiota transplantation group 3(FMT3). The control group was used as the donor of fecal microbiota transplantation, and the FMT1, FMT2, and FMT3 groups were intervened with mixed antibiotics(200 &#x3bc;L/d) for 2 weeks, and received fecal bacterial suspension(200 &#x3bc;L/d). The transplantation time of the FMT1 group frequency was 1 time/d for 1 weeks, the FMT2 group was 1 time/d for 2 weeks, and the FMT3 group was 3 times/week for 2 weeks. At the end of the experiment, the feces of the mice were collected to analyze the gut microbiota.<br><br>RESULTS: Compared with the control group, there were more independent Amplicon Sequence Variants in the intestinal microbiota of mice in FMT1 group, FMT2 group and FMT3 group, and the ACE index and Chao1 index were significantly reduced(P<0.05). Beta diversity showed differences between fecal microbiota transplantation and control groups, with FMT2 and control groups being the closest. At the phylum level, there were two species in FMT1 group and one species in FMT3 group showed statistically significant differences compared with control group(P<0.05). However, there was no significant difference between the FMT2 group and the control group. At the genus level, there were 6 species in the FMT1 with statistically significant differences from the control group(P<0.05), and 2 species in the FMT2, 5 species in the FMT3 respectively. Among which FMT2 group has the least number of species that differed from the control group, suggesting that the compitsition of its intestinal microbiota is closet to that of the control group.<br><br>CONCLUSION: Fecal bacteria transplantation helps to restore the intestinal microbiota structure of mice cleaned by antibiotics, and different transplantation frequencies and transplantation times have different recovery effects on the intestinal microbiota of mice pretreated with antibiotics, and the fecal bacteria transplantation effect is better with 1 time/d lasting 2 weeks.}, }
@article {pmid37678703, year = {2024}, author = {Meng, Y and Sun, J and Zhang, G}, title = {Pick fecal microbiota transplantation to enhance therapy for major depressive disorder.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {128}, number = {}, pages = {110860}, doi = {10.1016/j.pnpbp.2023.110860}, pmid = {37678703}, issn = {1878-4216}, abstract = {In recent years, fecal microbiota transplantation (FMT) has emerged as a promising therapy for major depressive disorder (MDD). The goal of the operation is to restore a healthy gut microbiota by introducing feces from a healthy donor into the recipient's digestive system. The brain-gut axis is thought to have a significant role in regulating mood, behavior, and cognition, which supports the use of FMT in the treatment of MDD. Numerous studies have shown a correlation between abnormalities of the gut microbiota and MDD, whereas FMT has demonstrated the potential to restore microbial equilibrium. While FMT has shown encouraging results, it is crucial to highlight the potential hazards and limits inherent to this therapeutic approach. Stool donor-to-recipient disease transfer is a concern of FMT. Furthermore, it still needs to be determined what effect FMT has on the gut microbiota and the brain in the long run. This literature review provides an overview of the possible efficacy of FMT as a therapeutic modality for MDD. There is hope for patients who have not reacted well to typical antidepressant therapy since FMT may become an invaluable tool in the treatment of MDD as researchers continue to examine the relationship between gut microbiota and MDD.}, }
@article {pmid37678377, year = {2023}, author = {Baker, KA and Poole, C}, title = {CE: Current and Emerging Applications of Fecal Microbiota Transplantation.}, journal = {The American journal of nursing}, volume = {123}, number = {10}, pages = {30-38}, doi = {10.1097/01.NAJ.0000978920.88346.77}, pmid = {37678377}, issn = {1538-7488}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Quality of Life ; Abdominal Pain ; Anti-Bacterial Agents ; Dehydration ; }, abstract = {Fecal microbiota transplantation (FMT) is a life-changing treatment for people with recurrent Clostridioides difficile infection (rCDI). Frequently acquired in the hospital, CDI can cause serious gastrointestinal symptoms, including persistent watery diarrhea, abdominal pain, and severe dehydration. Antibiotics, the primary treatment, can unfortunately disrupt the gut microbiome and lead to antimicrobial resistance. FMT involves introducing stool from a healthy donor into the affected recipient to strengthen their compromised microbiome. Individuals receiving this treatment have reported remarkable improvement in clinical outcomes and quality of life. In addition to a discussion of rCDI within the context of the gastrointestinal microbiome, this article provides an overview of the FMT procedure, discusses nursing management of individuals undergoing FMT, and highlights emerging applications beyond rCDI. A case scenario is also provided to illustrate a typical trajectory for a patient undergoing FMT.}, }
@article {pmid37678055, year = {2023}, author = {Gao, T and Li, Y and Wang, X and Tao, R and Ren, F}, title = {Bifidobacterium longum 68S mediated gut-skin axis homeostasis improved skin barrier damage in aging mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {120}, number = {}, pages = {155051}, doi = {10.1016/j.phymed.2023.155051}, pmid = {37678055}, issn = {1618-095X}, mesh = {Animals ; Mice ; *Bifidobacterium longum ; RNA, Ribosomal, 16S ; Aging ; Ceramides ; Disease Models, Animal ; Homeostasis ; }, abstract = {BACKGROUND: Bifidobacterium as probiotics, play important roles in skin status, while the potential mechanisms interaction remains unknown. The study further explored the potential mechanism of B. longum 68S in ameliorating skin barrier damage from the perspective of the gut-skin axis in aging mice.<br><br>METHODS: B. longum 68S supplied natural aging mouse model and fecal microbiota transplantation (FMT) experiment proves the key role of intestinal microbiota in B. longum 68S up-regulating the production of ceramide synthesis key enzyme (SPT1) and ceramide level and improving skin barrier damage. Moreover, B. longum 68S supplied SPT1 gene deletion mouse model to investigate the mechanism of B. longum 68S on improving skin barrier damage.<br><br>RESULTS: Transcriptome analysis and 16S rRNA high-throughput pyrosequencing demonstrated that aging mice exhibited skin barrier dysfunction and intestinal dysbiosis. Meanwhile, aging mice exhibited an up-regulation in the trans epidermal water loss (TEWL) and a down-regulation in the level of SPT1, ceramide and skin barrier-related proteins (Loricrin, Keratin 10 and Desmoglein 1). Similarity, the FMT from aging mice to normal mice and SPT1 gene deletion mice could rebuild skin barrier damage and B. longum 68S supplementation exerted a positive effect on it. Further, B. longum 68S-mediated SPT1-derived ceramide production prevented impaired ceramide synthesis-induced endoplasmic reticulum stress and apoptotic response, ultimately improving skin barrier damage in vitro.<br><br>CONCLUSION: Emerging anti-aging therapies are necessary given the poor safety profiles of current pharmaceutical drugs. B. longum 68S may be better alternatives, considering the association between the gut microbiota and healthy aging. The findings suggested that B. longum 68S-mediated gut-skin axis homeostasis, thereby exhibiting an anti-aging effect and facilitate a better understanding of the mechanisms governing the various beneficial effects of B. longum 68S.}, }
@article {pmid37677965, year = {2023}, author = {Wang, J and Guo, X and Zou, Z and Yu, M and Li, X and Xu, H and Chen, Y and Jiao, T and Wang, K and Ma, Y and Jiang, J and Liang, X and Wang, J and Xie, C and Zhong, Y}, title = {Ootheca mantidis mitigates renal fibrosis in mice by the suppression of apoptosis via increasing the gut microbe Akkermansia muciniphila and modulating glutamine metabolism.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {166}, number = {}, pages = {115434}, doi = {10.1016/j.biopha.2023.115434}, pmid = {37677965}, issn = {1950-6007}, mesh = {Akkermansia ; *Gastrointestinal Microbiome ; Apoptosis ; *Renal Insufficiency, Chronic ; Mice ; Glutamine ; *Ureteral Obstruction ; Animals ; Fibrosis ; }, abstract = {Renal interstitial fibrosis (RIF), a progressive process affecting the kidneys in chronic kidney disease (CKD), currently lacks an effective therapeutic intervention. Traditional Chinese medicine (TCM) has shown promise in reducing RIF and slowing CKD progression. In this study, we demonstrated the dose-dependent attenuation of RIF by Ootheca mantidis (SPX), a commonly prescribed TCM for CKD, in a mouse model of unilateral ureteral obstruction (UUO). RNA-sequencing analysis suggested that SPX treatment prominently downregulated apoptosis and inflammation-associated pathways, thereby inhibiting the fibrogenic signaling in the kidney. We further found that transplantation of fecal microbiota from SPX-treated mice conferred protection against renal injury and fibrosis through suppressing apoptosis in UUO mice, indicating that SPX ameliorated RIF via remodeling the gut microbiota and reducing apoptosis in the kidneys. Further functional exploration of the gut microbiota combined with fecal metabolomics revealed increased levels of some probiotics, including Akkermansia muciniphila (A. muciniphila), and modulations in glutamine-related amino acid metabolism in UUO mice treated with SPX. Subsequent colonization of A. muciniphila and supplementation with glutamine effectively mitigated cell apoptosis and RIF in UUO mice. Collectively, these findings unveil a functionally A. muciniphila- and glutamine-involved gut-renal axis that contributes to the action of SPX, and provide important clue for the therapeutic potential of SPX, A. muciniphila, and glutamine in combatting RIF.}, }
@article {pmid37676478, year = {2024}, author = {Wang, G and Jiang, Z and Song, Y and Xing, Y and He, S and Boomi, P}, title = {Gut microbiota contribution to selenium deficiency-induced gut-liver inflammation.}, journal = {BioFactors (Oxford, England)}, volume = {50}, number = {2}, pages = {311-325}, doi = {10.1002/biof.2006}, pmid = {37676478}, issn = {1872-8081}, support = {222102110290//Key R&amp;D and Promotion Projects in Henan Province/ ; 222102110381//Key R&amp;D and Promotion Projects in Henan Province/ ; 32102744//National Natural Science Foundation of China/ ; 202300410008//Natural Science Foundation of Henan Province/ ; }, mesh = {Mice ; Animals ; Lipopolysaccharides/pharmacology ; *Gastrointestinal Microbiome ; *Selenium/pharmacology ; Toll-Like Receptor 4/genetics/metabolism ; *Hepatitis ; Inflammation/genetics ; NF-kappa B/metabolism ; }, abstract = {There is limited knowledge about the factors that drive gut-liver axis changes after selenium (Se) deficiency-induced gut or liver injuries. Thus, we tested Se deficiency in mice to determine its effects on intestinal bacterial balance and whether it induced liver injury. Serum Se concentration, lipopolysaccharide (LPS) level, and liver injury biomarkers were tested using a biochemical method, while pathological changes in the liver and jejunum were observed via hematoxylin and eosin stain, and a fluorescence spectrophotometer was used to evaluate intestinal permeability. Tight junction (TJ)-related and toll-like receptor (TLR) signaling-related pathway genes and proteins were tested using quantitative polymerase chain reaction, western blotting, immunohistochemistry, and 16S ribosomal ribonucleic acid gene-targeted sequencing of jejunum microorganisms. Se deficiency significantly decreased glutathione peroxidase activity and disrupted the intestinal flora, with the most significant effect being a decrease in Lactobacillus reuteri. The expression of TJ-related genes and proteins decreased significantly with increased treatment time, whereas supplementation with Se, fecal microbiota transplantation, or L. reuteri reversed these decreases. Signs of liver injury and LPS content were significantly increased after intestinal flora imbalance or jejunum injury, and the levels of TLR signaling-related genes were significantly increased. The results indicated that Se deficiency disrupted the microbiota balance, decreased the expression of intestinal TJ factors, and increased intestinal permeability. By contrast, LPS increased due to a bacterial imbalance, which may induce inflammatory liver injury via the TLR4 signaling pathway.}, }
@article {pmid37675433, year = {2023}, author = {Wei, J and Chen, J and Fang, X and Liu, T and Yuan, Y and Zhang, J}, title = {Protocol for the safety and efficacy of fecal microbiota transplantation liquid in children with autism spectrum disorder: a randomized controlled study.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1236904}, pmid = {37675433}, issn = {1664-302X}, abstract = {BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, repetitive behavior and language impairment, and its worldwide prevalence has been found to be increasing annually in recent years. Till now, ASD is uncurable as its pathogenesis remains unknown. However, studies on both animals and humans have demonstrated that fecal microbiota transplantation (FMT) may ameliorate the symptoms of ASD, as well as gastrointestinal symptoms. Nonetheless, there is still no agreement regarding the optimal dosage or duration of FMT treatment for individuals with ASD.<br><br>METHODS: This clinical study is a double-blind, randomized, interventional trial conducted at a single center. The aim is to investigate the safety and efficacy of a pediatric formulation of FMT for ASD. A total of 42 children between the ages of 3-9 with ASD will be randomly assigned in a 2:1 ratio to either an FMT treatment group (n&#x2009;=&#x2009;28) or a placebo group (n&#x2009;=&#x2009;14), forming cohort 1. Additionally, 30 healthy children of similar age and gender will be recruited as the control group (cohort 2). Cohort 1 will be assessed using a variety of scales, including the Autism Behavior Checklist, Childhood Autism Rating Scale, Social Responsiveness Scale, Gastrointestinal Symptom Rating Scale, Children's Sleep Habits Questionnaire, and Psychoeducational Profile (Third Edition). These assessments will evaluate the effectiveness of FMT in reducing core symptoms and comorbidities (such as gastrointestinal symptoms and sleep disturbances) in children with ASD. The study will use metagenomic and metabolomic sequencing to assess changes in the composition and structure of the intestinal flora and its metabolites in blood, urine, and feces following treatment. Furthermore, the study will evaluate the acceptability of the FMT formulation by participants' legal guardians and investigate differences in the intestinal flora and metabolism in the FMT group before and after treatment compared to 30 healthy children.<br><br>CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/, identifier ChiCTR2200058459.}, }
@article {pmid37675126, year = {2023}, author = {Shan, H and Wei, C and Zhang, J and He, M and Zhang, Z}, title = {Case Report: Severe Diarrhea Caused by Cryptosporidium Diagnosed by Metagenome Next-Generation Sequencing in Blood.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {5777-5782}, pmid = {37675126}, issn = {1178-6973}, abstract = {BACKGROUND: Cryptosporidium is one of the major pathogens causing diarrhea worldwide. At present, cryptosporidiosis is difficult to prevent and control, especially in immunocompromised hosts. It may cause life-threatening diarrhea and malabsorption among children and immunocompromised patients. Therefore, it is very important to explore rapid diagnostic tools and treatment methods for Cryptosporidium infection.<br><br>CASE PRESENTATION: We reported a case of severe diarrhea caused by cryptosporidiosis in a liver transplant recipient, whose condition was finally confirmed by metagenomic next-generation sequencing (mNGS) and fecal microscopy. His illness was resolved with immunosuppression regulation, nitazoxanide administration, and infection control.<br><br>CONCLUSION: So far, nitazoxanide is still the first choice for the treatment of cryptosporidiosis. Our institutional experience suggested that nitazoxanide alone may be effective on the basis of adjusting immunosuppressant. In addition, even though diagnosis of Cryptosporidium infection is a challenge, mNGS can serve as a rapid screening tool in low-prevalence setting.}, }
@article {pmid37674043, year = {2024}, author = {Ma, XZ and Chen, LL and Qu, L and Li, H and Wang, J and Song, N and Xie, JX}, title = {Gut microbiota-induced CXCL1 elevation triggers early neuroinflammation in the substantia nigra of Parkinsonian mice.}, journal = {Acta pharmacologica Sinica}, volume = {45}, number = {1}, pages = {52-65}, pmid = {37674043}, issn = {1745-7254}, mesh = {Mice ; Animals ; Male ; Rotenone/toxicity ; Neuroinflammatory Diseases ; *Gastrointestinal Microbiome ; PPAR gamma ; Mice, Inbred C57BL ; *Parkinson Disease/pathology ; Substantia Nigra/pathology ; Dopaminergic Neurons/pathology ; Inflammation/pathology ; Iron ; Disease Models, Animal ; }, abstract = {Gut microbiota disturbance and systemic inflammation have been implicated in the degeneration of dopaminergic neurons in Parkinson's disease (PD). How the alteration of gut microbiota results in neuropathological events in PD remains elusive. In this study, we explored whether and how environmental insults caused early neuropathological events in the substantia nigra (SN) of a PD mouse model. Aged (12-month-old) mice were orally administered rotenone (6.25 mg·kg[-1]·d[-1]) 5 days per week for 2 months. We demonstrated that oral administration of rotenone to ageing mice was sufficient to establish a PD mouse model and that microglial activation and iron deposition selectively appeared in the SN of the mice prior to loss of motor coordination and dopaminergic neurons, and these events could be fully blocked by microglial elimination with a PLX5622-formulated diet. 16 S rDNA sequencing analysis showed that the gut microbiota in rotenone-treated mice was altered, and mice receiving faecal microbial transplantation (FMT) from ageing mice treated with rotenone for 2 months exhibited the same pathology in the SN. We demonstrated that C-X-C motif chemokine ligand-1 (CXCL1) was an essential molecule, as intravenous injection of CXCL1 mimicked almost all the pathology in serum and SN induced by oral rotenone and FMT. Using metabolomics and transcriptomics analyses, we identified the PPAR pathway as a key pathway involved in rotenone-induced neuronal damage. Inhibition of the PPARγ pathway was consistent in the above models, whereas its activation by linoleic acid (60 mg·kg[-1]·d[-1], i.g. for 1 week) could block these pathological events in mice intravenously injected with CXCL1. Altogether, these results reveal that the altered gut microbiota resulted in neuroinflammation and iron deposition occurring early in the SN of ageing mice with oral administration of rotenone, much earlier than motor symptoms and dopaminergic neuron loss. We found that CXCL1 plays a crucial role in this process, possibly via PPARγ signalling inhibition. This study may pave the way for understanding the "brain-gut-microbiota" molecular regulatory networks in PD pathogenesis. The aged C57BL/6 male mice with rotenone intragastric administration showed altered gut microbiota, which caused systemic inflammation, PPARγ signalling inhibition and neuroinflammation, brain iron deposition and ferroptosis, and eventually dopaminergic neurodegeneration in PD.}, }
@article {pmid37673907, year = {2023}, author = {Xia, Y and Xiao, Y and Wang, ZH and Liu, X and Alam, AM and Haran, JP and McCormick, BA and Shu, X and Wang, X and Ye, K}, title = {Bacteroides Fragilis in the gut microbiomes of Alzheimer's disease activates microglia and triggers pathogenesis in neuronal C/EBPβ transgenic mice.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5471}, pmid = {37673907}, issn = {2041-1723}, support = {P20 GM130456/GM/NIGMS NIH HHS/United States ; R01 AG065177/AG/NIA NIH HHS/United States ; R01 AG067483/AG/NIA NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; }, mesh = {Mice ; Animals ; Bacteroides fragilis/genetics ; Mice, Transgenic ; *Gastrointestinal Microbiome ; *Alzheimer Disease/therapy ; Dinoprostone ; Microglia ; RNA, Ribosomal, 16S/genetics ; Bacteroides ; *Bacterial Infections ; Hydroxy Acids ; }, abstract = {Gut dysbiosis contributes to Alzheimer's disease (AD) pathogenesis, and Bacteroides strains are selectively elevated in AD gut microbiota. However, it remains unknown which Bacteroides species and how their metabolites trigger AD pathologies. Here we show that Bacteroides fragilis and their metabolites 12-hydroxy-heptadecatrienoic acid (12-HHTrE) and Prostaglandin E2 (PGE2) activate microglia and induce AD pathogenesis in neuronal C/EBPβ transgenic mice. Recolonization of antibiotics cocktail-pretreated Thy1-C/EBPβ transgenic mice with AD patient fecal samples elicits AD pathologies, associated with C/EBPβ/Asparaginyl endopeptidase (AEP) pathway upregulation, microglia activation, and cognitive disorders compared to mice receiving healthy donors' fecal microbiota transplantation (FMT). Microbial 16S rRNA sequencing analysis shows higher abundance of proinflammatory Bacteroides fragilis in AD-FMT mice. Active components characterization from the sera and brains of the transplanted mice revealed that both 12-HHTrE and PGE2 activate primary microglia, fitting with poly-unsaturated fatty acid (PUFA) metabolites enrichment identified by metabolomics. Strikingly, recolonization with live but not dead Bacteroides fragilis elicited AD pathologies in Thy1-C/EBPβ transgenic mice, so did 12-HHTrE or PGE2 treatment alone. Collectively, our findings support a causal role for Bacteroides fragilis and the PUFA metabolites in activating microglia and inducing AD pathologies in Thy1- C/EBPβ transgenic mice.}, }
@article {pmid37673036, year = {2023}, author = {Ni, Y and Qian, L and Siliceo, SL and Long, X and Nychas, E and Liu, Y and Ismaiah, MJ and Leung, H and Zhang, L and Gao, Q and Wu, Q and Zhang, Y and Jia, X and Liu, S and Yuan, R and Zhou, L and Wang, X and Li, Q and Zhao, Y and El-Nezami, H and Xu, A and Xu, G and Li, H and Panagiotou, G and Jia, W}, title = {Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations.}, journal = {Cell metabolism}, volume = {35}, number = {9}, pages = {1530-1547.e8}, doi = {10.1016/j.cmet.2023.08.002}, pmid = {37673036}, issn = {1932-7420}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Microbiota ; *Non-alcoholic Fatty Liver Disease ; Resistant Starch ; Triglycerides ; Humans ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic dysfunction for which effective interventions are lacking. To investigate the effects of resistant starch (RS) as a microbiota-directed dietary supplement for NAFLD treatment, we coupled a 4-month randomized placebo-controlled clinical trial in individuals with NAFLD (ChiCTR-IOR-15007519) with metagenomics and metabolomics analysis. Relative to the control (n = 97), the RS intervention (n = 99) resulted in a 9.08% absolute reduction of intrahepatic triglyceride content (IHTC), which was 5.89% after adjusting for weight loss. Serum branched-chain amino acids (BCAAs) and gut microbial species, in particular Bacteroides stercoris, significantly correlated with IHTC and liver enzymes and were reduced by RS. Multi-omics integrative analyses revealed the interplay among gut microbiota changes, BCAA availability, and hepatic steatosis, with causality supported by fecal microbiota transplantation and monocolonization in mice. Thus, RS dietary supplementation might be a strategy for managing NAFLD by altering gut microbiota composition and functionality.}, }
@article {pmid37672855, year = {2023}, author = {Xia, X and Zhang, Y and Zhu, L and Ying, Y and Hao, W and Wang, L and He, L and Zhao, D and Chen, JX and Gao, Y and Huang, JQ}, title = {Liquiritin apioside alleviates colonic inflammation and accompanying depression-like symptoms in colitis by gut metabolites and the balance of Th17/Treg.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {120}, number = {}, pages = {155039}, doi = {10.1016/j.phymed.2023.155039}, pmid = {37672855}, issn = {1618-095X}, mesh = {Humans ; Animals ; Mice ; Depression/drug therapy ; RNA, Ribosomal, 16S ; T-Lymphocytes, Regulatory ; *Colitis/drug therapy ; Inflammation ; *Inflammatory Bowel Diseases ; Cytokines ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a significant global health concern that can lead to depression in affected patients. Liquiritin apioside (LA) possesses anti-oxidative and anti-inflammatory properties. However, its anti-inflammatory mechanism in IBD has not been extensively studied.<br><br>PURPOSE: This study elucidates the pivotal role of LA in alleviating inflammation by regulating gut metabiota-derived metabolites and evaluating its regulative effects on promoting a balance of Th17/Treg cells in colitis mice.<br><br>METHODS: To evaluate the effect of LA on IBD,16S rRNA gene sequencing and UPLC-QTOF-MS analysis were used to identify the changes of intestinal bacteria and their metabolites. Cytokines levels were determined by ELISA and qPCR, while immune cell ratios were evaluated via flow cytometry.<br><br>RESULTS: Our findings revealed that LA treatment ameliorated general states of DSS-induced colitis mice and their accompanying depressive behaviors. Moreover, LA restricted the expression of pro-inflammatory cytokines and revised the imbalanced Treg/Th17 differentiation, while promoting SCFAs production in inflamed colon tissues. Fecal microbiota transplantation from LA-fed mice also corrected the imbalanced Treg/Th17 differentiation, indicating that LA-mediated restoration of the colonic Treg/Th17 balance mainly depends on the changes in gut metabolites.<br><br>CONCLUSION: These results provide scientific evidence explaining the apparent paradox of low bioavailability and high bioactivity in polyphenols, and suggesting that LA could be used as a potential dietary supplement for the prevention and improvement of IBD.}, }
@article {pmid37671830, year = {2024}, author = {Xia, K and Gao, R and Li, L and Wu, X and Wu, T and Ruan, Y and Yin, L and Chen, C}, title = {Transformation of colitis and colorectal cancer: a tale of gut microbiota.}, journal = {Critical reviews in microbiology}, volume = {50}, number = {5}, pages = {653-662}, doi = {10.1080/1040841X.2023.2254388}, pmid = {37671830}, issn = {1549-7828}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Colorectal Neoplasms/microbiology ; *Colitis/microbiology ; Animals ; Probiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Prebiotics/administration &amp; dosage ; }, abstract = {Intestinal inflammation modifies host physiology to promote the occurrence of colorectal cancer (CRC), as seen in colitis-associated CRC. Gut microbiota is crucial in cancer progression, primarily by inducing intestinal chronic inflammatory microenvironment, leading to DNA damage, chromosomal mutation, and alterations in specific metabolite production. Therefore, there is an increasing interest in microbiota-based prevention and treatment strategies, such as probiotics, prebiotics, microbiota-derived metabolites, and fecal microbiota transplantation. This review aims to provide valuable insights into the potential correlations between gut microbiota and colitis-associated CRC, as well as the promising microbiota-based strategies for colitis-associated CRC.}, }
@article {pmid37671803, year = {2023}, author = {Li, N and Tan, S and Wang, Y and Deng, J and Wang, N and Zhu, S and Tian, W and Xu, J and Wang, Q}, title = {Akkermansia muciniphila supplementation prevents cognitive impairment in sleep-deprived mice by modulating microglial engulfment of synapses.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2252764}, pmid = {37671803}, issn = {1949-0984}, mesh = {Dietary Supplements ; *Cognitive Dysfunction ; Akkermansia ; *Gastrointestinal Microbiome ; Sleep Deprivation ; Dysbiosis ; Synapses ; Microglia ; Sleep ; Mice ; Animals ; }, abstract = {The microbiome-gut-brain axis plays a crucial role in many neurological diseases, including mild cognitive impairment. Sleep deprivation (SD) induces cognitive decline accompanied by alterations in the gut microbiota. However, the role of gut microbiota alterations in SD-induced cognitive dysfunction and the underlying mechanisms remain unclear. Here, we found that dysbiosis of the gut microbiota following pretreatment with broad-spectrum antibiotics worsens SD-induced cognitive impairment in mice. Fecal microbiota transplantation from SD mice to healthy mice induced cognitive impairment. Additionally, the abundance of Akkermansia muciniphila (A. muciniphila) in the mouse gut microbiota was significantly reduced after 7 days of SD. A. muciniphila pretreatment alleviated cognitive dysfunction and prevented synaptic reduction in the hippocampus in SD mice. A. muciniphila pretreatment inhibited extensive microglial activation and synaptic engulfment in the hippocampus of SD mice. Metabolomics analysis revealed that A. muciniphila pretreatment increased the serum acetate and butanoic acid levels in SD mice. Finally, pretreatment with short-chain fatty acids (SCFAs) inhibited microglial synaptic engulfment and prevented neuronal synaptic loss in SD mice and primary microglia-neuron co-culture following LPS stimulation. Together, our findings illustrate that gut dysbiosis plays an essential role in SD-induced cognitive impairment by activating microglial engulfment at synapses. A. muciniphila supplementation may be a novel preventative strategy for SD-induced cognitive dysfunction, by increasing SCFAs production and maintaining microglial homeostasis.}, }
@article {pmid37668964, year = {2024}, author = {Zhang, Y and Liu, J and Liu, X and Zhou, Y and Geng, J and Shi, Z and Ma, L}, title = {Fecal Microbiota Transplantation-Mediated Ghrelin Restoration Improves Neurological Functions After Traumatic Brain Injury: Evidence from 16S rRNA Sequencing and In Vivo Studies.}, journal = {Molecular neurobiology}, volume = {61}, number = {2}, pages = {919-934}, pmid = {37668964}, issn = {1559-1182}, mesh = {Rats ; Animals ; *Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; Ghrelin ; *Brain Injuries, Traumatic/therapy ; Glucagon-Like Peptide 1 ; }, abstract = {This study aimed to investigate how gut microbiota dysbiosis impacts the repair of the blood-brain barrier and neurological deficits following traumatic brain injury (TBI). Through 16S rRNA sequencing analysis, we compared the gut microbiota of TBI rats and normal controls, discovering significant differences in abundance, species composition, and ecological function, potentially linked to Ghrelin-mediated brain-gut axis functionality. Further, in vivo experiments showed that fecal microbiota transplantation or Ghrelin injection could block the intracerebral TNF signaling pathway, enhance GLP-1 expression, significantly reduce brain edema post-TBI, promote the repair of the blood-brain barrier, and improve neurological deficits. However, the TNF signaling pathway activation could reverse these beneficial effects. In summary, our research suggests that by restoring the balance of gut microbiota, the levels of Ghrelin can be elevated, leading to the blockade of intracerebral TNF signaling pathway and enhanced GLP-1 expression, thereby mitigating post-TBI blood-brain barrier disruption and neurological injuries.}, }
@article {pmid37668317, year = {2023}, author = {Mendes de Almeida, V and Engel, DF and Ricci, MF and Cruz, CS and Lopes, &#xcd;S and Alves, DA and d' Auriol, M and Magalhães, J and Machado, EC and Rocha, VM and Carvalho, TG and Lacerda, LSB and Pimenta, JC and Aganetti, M and Zuccoli, GS and Smith, BJ and Carregari, VC and da Silva Rosa, E and Galvão, I and Dantas Cassali, G and Garcia, CC and Teixeira, MM and André, LC and Ribeiro, FM and Martins, FS and Saia, RS and Costa, VV and Martins-de-Souza, D and Hansbro, PM and Marques, JT and Aguiar, ERGR and Vieira, AT}, title = {Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2249146}, pmid = {37668317}, issn = {1949-0984}, mesh = {Animals ; Mice ; *COVID-19 ; *Gastrointestinal Microbiome ; SARS-CoV-2 ; Anti-Bacterial Agents ; Disease Progression ; }, abstract = {Long-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut microbiota, which is linked to disease severity in patients with COVID-19. Here, we report that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with an antibiotic-resistant phenotype compared to healthy controls. Additionally, short-chain fatty acid (SCFA) levels were reduced in feces. Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae. transplanted mice also exhibited poor cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection on the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target.}, }
@article {pmid37667968, year = {2023}, author = {Yau, YK and Su, Q and Xu, Z and Tang, W and Ching, JYL and Mak, JWY and Cheung, CP and Fung, M and Ip, M and Chan, PKS and Wu, JCY and Chan, FKL and Ng, SC}, title = {Randomised clinical trial: Faecal microbiota transplantation for irritable bowel syndrome with diarrhoea.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {58}, number = {8}, pages = {795-804}, doi = {10.1111/apt.17703}, pmid = {37667968}, issn = {1365-2036}, mesh = {Humans ; *Irritable Bowel Syndrome/microbiology ; Fecal Microbiota Transplantation/adverse effects ; *Hydrogen Sulfide ; Diarrhea/therapy/etiology ; Feces/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has been shown to improve symptoms in a proportion of patients with irritable bowel syndrome (IBS).<br><br>AIM: We performed a randomised trial to assess the efficacy of FMT in patients with IBS.<br><br>METHODS: We randomised 56 patients with diarrhoea-predominant IBS 1:1 to FMT or placebo via the duodenal route at baseline and week 4. The primary outcome was > 50 points decrease in IBS severity scoring system (IBS-SSS) score at week 12. Secondary outcomes were improvement in bloating and change in gut microbiota at week 12. After 12-week follow-up, those in the placebo group were assigned to receive open-label FMT.<br><br>RESULTS: At week 12, 57.1% in the FMT group and 46.4% in the placebo group achieved the primary endpoint (p&#x2009;=&#x2009;0.42). More patients receiving FMT than placebo had improvement in bloating (72% vs 30%; p&#x2009;=&#x2009;0.005). In an open-label extension, 65.2% and 82.4% of patients achieved, respectively, the primary endpoint and improvement in bloating. Faecal microbiome of patients in the FMT group showed a reduction in bacteria like Ruminococcus gnavus and enrichment of bacteria such as Lawsonibacter at week 12, while no change in the placebo group. Functional analyses showed that the hydrogen sulphide-producing pathway decreased in patients who had FMT (p&#x2009;<&#x2009;0.05) accompanied by a reduction in contributing bacteria. There were no serious adverse events related to FMT.<br><br>CONCLUSION: FMT performed twice at an interval of four weeks did not significantly reduce IBS-SSS score. However, more patients had improvement in abdominal bloating, which was associated with a reduction in hydrogen sulphide-producing bacteria. (ClinicalTrials.gov NCT03125564).}, }
@article {pmid37667688, year = {2023}, author = {Feuerstadt, P and Oneto, C and Tillotson, G and Van Hise, NW}, title = {Patient Perception of Route of Rectal Administration of Live Biotherapeutic Product for Recurrent Clostridioides difficile Infection.}, journal = {Patient preference and adherence}, volume = {17}, number = {}, pages = {2153-2159}, pmid = {37667688}, issn = {1177-889X}, abstract = {INTRODUCTION: CDI is a recurrent disease that is treated with antibiotics, but patients commonly experience repeat infections with significant impacts on hospital budgets and patient health quality. Standard of care management includes the antibiotics, vancomycin and fidaxomicin, which frequently provide clinical response, but do not avoid recurrence of Clostridioides difficile infection (rCDI). These recurrent infections occur due to dysbiosis of the colonic microbiota. One adjunctive therapeutic approach is to restore the deficient gastrointestinal flora using fecal microbiota transplantation (FMT) or live biotherapeutic products (LBP) when given after standard of care antimicrobials, which have been successful in reducing repeat infections with success rates up to 88%. FMT or LBP can be given by various routes.<br><br>METHODS: Two groups of subjects aged &#x2265;18 years with at least one previous CDI episode within the previous 36 months completed self-administered online surveys to assess the acceptability of an LBP administered rectally. Group 1 consisted of LBP-recipients who had received RBL (REBYOTA) rectally as part of the Phase III PUNCH CD3 clinical trial. Group 2 consisted of LBP-na&#xef;ve subjects who volunteered to participate and had experienced CDI within the prior 36 months but had no history of receiving FMT or LBP therapy.<br><br>RESULTS: LBP-recipients considered rectal administration easy (96%) and quick (94%), while 98% of respondents considered the lack of need for bowel preparation appealing. Most LBP-recipients (96%) wished they had earlier access to RBL. Most LBP-na&#xef;ve subjects (87%) were likely or somewhat likely to consider a rectally administered treatment and 80% preferred a treatment option that does not require bowel preparation. Many of these subjects (76%) expressed interest in finding out about new treatment options for rCDI.<br><br>DISCUSSION: LBP-recipients and LBP-na&#xef;ve subjects alike felt that rectal delivery of microbiome therapy is not only acceptable but highly interesting as a treatment avenue.}, }
@article {pmid37667277, year = {2023}, author = {Hotta, R and Rahman, A and Bhave, S and Stavely, R and Pan, W and Srinivasan, S and de Couto, G and Rodriguez-Borlado, L and Myers, R and Burns, AJ and Goldstein, AM}, title = {Transplanted ENSCs form functional connections with intestinal smooth muscle and restore colonic motility in nNOS-deficient mice.}, journal = {Stem cell research &amp; therapy}, volume = {14}, number = {1}, pages = {232}, pmid = {37667277}, issn = {1757-6512}, mesh = {Animals ; Mice ; *Neurons ; *Muscle, Smooth ; Cell- and Tissue-Based Therapy ; Colon ; Electric Stimulation ; }, abstract = {BACKGROUND: Enteric neuropathies, which result from abnormalities of the enteric nervous system, are associated with significant morbidity and high health-care costs, but current treatments are unsatisfactory. Cell-based therapy offers an innovative approach to replace the absent or abnormal enteric neurons and thereby restore gut function.<br><br>METHODS: Enteric neuronal stem cells (ENSCs) were isolated from the gastrointestinal tract of Wnt1-Cre;R26tdTomato mice and generated neurospheres (NS). NS transplants were performed via injection into the mid-colon mesenchyme of nNOS[-/-] mouse, a model of colonic dysmotility, using either 1 (n&#x2009;=&#x2009;12) or 3 (n&#x2009;=&#x2009;12) injections (30 NS per injection) targeted longitudinally 1-2&#xa0;mm apart. Functional outcomes were assessed up to 6&#xa0;weeks later using electromyography (EMG), electrical field stimulation (EFS), optogenetics, and by measuring colorectal motility.<br><br>RESULTS: Transplanted ENSCs formed nitrergic neurons in the nNOS[-/-] recipient colon. Multiple injections of ENSCs resulted in a significantly larger area of coverage compared to single injection alone and were associated with a marked improvement in colonic function, demonstrated by (1) increased colonic muscle activity by EMG recording, (2) faster rectal bead expulsion, and (3) increased fecal pellet output in vivo. Organ bath studies revealed direct neuromuscular communication by optogenetic stimulation of channelrhodopsin-expressing ENSCs and restoration of smooth muscle relaxation in response to EFS.<br><br>CONCLUSIONS: These results demonstrate that transplanted ENSCs can form effective neuromuscular connections and improve colonic motor function in a model of colonic dysmotility, and additionally reveal that multiple sites of cell delivery led to an improved response, paving the way for optimized clinical trial design.}, }
@article {pmid37665106, year = {2023}, author = {}, title = {Retraction statement: Role of the immune system in vascular function and blood pressure control induced by faecal microbiota transplantation in rats.}, journal = {Acta physiologica (Oxford, England)}, volume = {239}, number = {4}, pages = {e14039}, doi = {10.1111/apha.14039}, pmid = {37665106}, issn = {1748-1716}, abstract = {Toral, M, Robles-Vera, I, de la Visitación, N, et al. Role of the immune system in vascular function and blood pressure control induced by faecal microbiota transplantation in rats. Acta Physiol. 2019; 227:e13285. https://doi.org/10.1111/apha.13285. The above article, published online on April 20, 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Pontus B. Persson, the Scandinavian Physiological Society, and John Wiley and Sons Ltd. The retraction has been agreed due to the similarity of a figure and inconsistencies regarding underlying data between this article and the following article published in Front Physiol, "Critical Role of the Interaction Gut Microbiota-Sympathetic Nervous System in the Regulation of Blood Pressure" by Toral M, Robles-Vera I, de la Visitación N, et al., 2019; 10:231. doi: 10.3389/fphys.2019.00231.}, }
@article {pmid37665061, year = {2023}, author = {Yang, J and Shi, X and Gao, R and Fan, L and Chen, R and Cao, Y and Xu, T and Yang, J}, title = {Polydatin alleviates bleomycin-induced pulmonary fibrosis and alters the gut microbiota in a mouse model.}, journal = {Journal of cellular and molecular medicine}, volume = {27}, number = {23}, pages = {3717-3728}, pmid = {37665061}, issn = {1582-4934}, support = {81774231//Data Center of Management Science, National Natural Science Foundation of China - Peking University/ ; 82174300//Data Center of Management Science, National Natural Science Foundation of China - Peking University/ ; }, mesh = {Mice ; Animals ; *Pulmonary Fibrosis/chemically induced/therapy/metabolism ; Bleomycin/pharmacology ; *Gastrointestinal Microbiome ; Lung/pathology ; Fibrosis ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Mice, Inbred C57BL ; }, abstract = {To investigate the effect and mechanism of polydatin on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model. The lung fibrosis model was induced by BLM. The contents of TNF-α, LPS, IL-6 and IL-1β in lung tissue, intestine and serum were detected by ELISA. Gut microbiota diversity was detected by 16S rDNA sequencing; R language was used to analyse species composition, α-diversity, β-diversity, species differences and marker species. Mice were fed drinking water mixed with four antibiotics (ampicillin, neomycin, metronidazole, vancomycin; antibiotics, ABx) to build a mouse model of ABx-induced bacterial depletion; and faecal microbiota from different groups were transplanted into BLM-treated or untreated ABx mice. The histopathological changes and collagen I and α-SMA expression were determined. Polydatin effectively reduced the degree of fibrosis in a BLM-induced pulmonary fibrosis mouse model; BLM and/or polydatin affected the abundance of the dominant gut microbiota in mice. Moreover, faecal microbiota transplantation (FMT) from polydatin-treated BLM mice effectively alleviated lung fibrosis in BLM-treated ABx mice compared with FMT from BLM mice. Polydatin can reduce fibrosis and inflammation in a BLM-induced mouse pulmonary fibrosis model. The alteration of gut microbiota by polydatin may be involved in the therapeutic effect.}, }
@article {pmid37663603, year = {2023}, author = {Hu, C and He, T and Zou, B and Li, H and Zhao, J and Hu, C and Cui, J and Huang, Z and Shu, S and Hao, Y}, title = {Fecal microbiota transplantation in a child with severe ASD comorbidities of gastrointestinal dysfunctions-a case report.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1219104}, pmid = {37663603}, issn = {1664-0640}, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by social communication impairments and restricted, repetitive behaviors. In addition to behavioral interventions and psychotherapies, and pharmacological interventions, in-depth studies of intestinal microbiota in ASD has obvious abnormalities which may effectively influenced in ASD. Several attempts have been made to indicate that microbiota can reduce the occurrence of ASD effectively. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient's gastrointestinal tract to improve the gut microenvironment. In this case report, we describe a case of child ASD treated by FMT. The patient have poor response to long-term behavioral interventions. After five rounds of FMT, clinical core symptoms of ASD and gastrointestinal(GI) symptoms were significantly altered. Moreover, the multiple levels of functional development of child were also significantly ameliorated. We found that FMT changed the composition of the intestinal microbiota as well as the metabolites, intestinal inflammatory manifestations, and these changes were consistent with the patient's symptoms. This report suggests further FMT studies in ASD could be worth pursuing, and more studies are needed to validate the effectiveness of FMT in ASD and its mechanisms.}, }
@article {pmid37662996, year = {2023}, author = {Hsieh, JC and Chuang, ST and Hsu, YT and Ho, ST and Li, KY and Chou, SH and Chen, MJ}, title = {In vitro ruminal fermentation and cow-to-mouse fecal transplantations verify the inter-relationship of microbiome and metabolome biomarkers: potential to promote health in dairy cows.}, journal = {Frontiers in veterinary science}, volume = {10}, number = {}, pages = {1228086}, pmid = {37662996}, issn = {2297-1769}, abstract = {INTRODUCTION: There are differences in the gut microbiome and metabolome when the host undergoes different physical or pathological conditions. However, the inter-relationship of microbiome and metabolome biomarkers to potentially promote the health of dairy cows needs to be studied. Further, the development of next-generation probiotics for dairy cattle health promotion has not been demonstrated.<br><br>OBJECTIVE: In the present study, we identified the microbiome and metabolome biomarkers associated with healthy cows.<br><br>METHODS: We analyzed the relationships of the ruminal microorganism profile and metabolites between healthy and mastitis lactating dairy cows. The roles of bacterial biomarker were further verified by in vitro fermentation and cow-to-mouse fecal microbiota transplantation (FMT).<br><br>RESULTS: Two species, Ruminococcus flavefaciens and Bifidobacterium longum subsp. longum, and six rumen metabolites were positively correlated with healthy cows by Spearman's correlation analysis. Through in vitro ruminal fermentation, inoculating R. flavefaciens and B. longum subsp. longum showed the upregulation of the levels of putrescine, xanthurenic acid, and pyridoxal in the mastitis ruminal fluid, which confirmed the inter-relationships between these microbiota and metabolites associated with healthy cows. Further, we verified the role of R. flavefaciens and B. longum subsp. longum in promoting health by FMT. The administration of R. flavefaciens and B. longum subsp. longum reduced the death rate and recovered the bodyweight loss of germ-free mice caused by FMT mastitis feces.<br><br>DISCUSSION: We provided evidence that the bacterial biomarkers alter downstream metabolites. This could indirectly indicate that the two bacterial biomarkers have the potential to be used as next-generation probiotics for dairy cattle, although it needs more evidence to support our hypothesis. Two species, R. flavefaciens and B. longum subsp. longum, with three metabolites, putrescine, xanthurenic acid, and pyridoxal, identified in the ruminal fluid, may point to a new health-promoting and disease-preventing approach for dairy cattle.}, }
@article {pmid37662857, year = {2023}, author = {Wen, X and Xie, R and Wang, HG and Zhang, MN and He, L and Zhang, MH and Yang, XZ}, title = {Fecal microbiota transplantation alleviates experimental colitis through the Toll-like receptor 4 signaling pathway.}, journal = {World journal of gastroenterology}, volume = {29}, number = {30}, pages = {4657-4670}, pmid = {37662857}, issn = {2219-2840}, mesh = {Animals ; Mice ; *Colitis/chemically induced/therapy ; *Colitis, Ulcerative/chemically induced/genetics/therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Signal Transduction ; *Toll-Like Receptor 4/genetics ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis (UC). FMT modulates the Toll-like receptor 4 (TLR4) signaling pathway to treat some other diseases. However, it remains unknown whether this modulation is also involved in the treatment of UC.<br><br>AIM: To clarify the necessity of TLR4 signaling pathway in FMT on dextran sodium sulphate (DSS)-induced mice and explain the mechanism of FMT on UC, through association analysis of gut microbiota with colon transcriptome in mice.<br><br>METHODS: A mouse colitis model was constructed with wild-type (WT) and TLR4-knockout (KO) mice. Fecal microbiota was transplanted by gavage. Colon inflammation severity was measured by disease activity index (DAI) scoring and hematoxylin and eosin staining. Gut microbiota structure was analyzed through 16S ribosomal RNA sequencing. Gene expression in the mouse colon was obtained by transcriptome sequencing.<br><br>RESULTS: The KO (DSS + Water) and KO (DSS + FMT) groups displayed indistinguishable body weight loss, colon length, DAI score, and histology score, which showed that FMT could not inhibit the disease in KO mice. In mice treated with FMT, the relative abundance of Akkermansia decreased, and Lactobacillus became dominant. In particular, compared with those in WT mice, the scores of DAI and colon histology were clearly decreased in the KO-DSS group. Microbiota structure showed a significant difference between KO and WT mice. Akkermansia were the dominant genus in healthy KO mice. The ineffectiveness of FMT in KO mice was related to the decreased abundance of Akkermansia. Gene Ontology enrichment analysis showed that differentially expressed genes between each group were mainly involved in cytoplasmic translation and cellular response to DNA damage stimulus. The top nine genes correlating with Akkermansia included Aqp4, Clca4a, Dpm[3], Fau, Mcrip1, Meis3, Nupr1 L, Pank3, and Rps13 (|R| > 0.9, P < 0.01).<br><br>CONCLUSION: FMT may ameliorate DSS-induced colitis by regulating the TLR4 signaling pathway. TLR4 modulates the composition of gut microbiota and the expression of related genes to ameliorate colitis and maintain the stability of the intestinal environment. Akkermansia bear great therapeutic potential for colitis.}, }
@article {pmid37661203, year = {2023}, author = {Feng, J and Chen, Y and Liu, Y and Lin, L and Lin, X and Gong, W and Xia, R and He, J and Sheng, J and Cai, H and Xiao, C}, title = {Efficacy and safety of fecal microbiota transplantation in the treatment of ulcerative colitis: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {14494}, pmid = {37661203}, issn = {2045-2322}, mesh = {Humans ; *Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation/adverse effects ; Databases, Factual ; MEDLINE ; Odds Ratio ; Randomized Controlled Trials as Topic ; }, abstract = {To explore the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment approach for ulcerative colitis (UC), a comprehensive systematic review and meta-analysis of randomized controlled trials was conducted. To collect and evaluate randomized controlled trials of high quality on FMT for UC, we searched a number of databases, including PubMed, Web of Science, Cochrane, Embase, and Medline, for studies published between the establishment of the databases and March 2023. We conducted a meta-analysis of the studies using Review Manager software (version 5.4.1) to determine the differences in rates of remission and adverse reactions between the FMT group and the control group, utilizing the risk ratio (RR) and 95% confidence interval (CI) to combine our findings. A total of 13 randomized controlled trials (RCTs) on the efficacy of FMT in patients with UC were included in the study, in which 580 patients participated, including 293 patients treated with FMT and 287 control subjects. Meta-analysis revealed that clinical remission was significantly better in the FMT group than in the control group [RR = 1.73; 95% CI = (1.41, 2.12); P < 0.00001]; endoscopic remission was significantly better in the FMT group than in the control group [RR = 1.74; 95% CI = (1.24, 2.44); P = 0.001]. Additionally, there were no significant differences in the incidence of adverse reactions between the two groups [RR = 1.00; 95% CI = (0.86, 1.15); P = 0.96]. Fecal microbiota transplantation has shown potential as a therapeutic intervention for inducing clinical remission in ulcerative colitis UC; nevertheless, the attainment of endoscopic remission and the maintenance of long-term remission continue to present challenges. Safety concerns persist throughout the treatment process, necessitating the implementation of measures to augment both safety and success rates.}, }
@article {pmid37661007, year = {2024}, author = {McGuinness, AJ and Loughman, A and Foster, JA and Jacka, F}, title = {Mood Disorders: The Gut Bacteriome and Beyond.}, journal = {Biological psychiatry}, volume = {95}, number = {4}, pages = {319-328}, doi = {10.1016/j.biopsych.2023.08.020}, pmid = {37661007}, issn = {1873-2402}, mesh = {Humans ; Mood Disorders ; *Depressive Disorder, Major ; Ecosystem ; *Gastrointestinal Microbiome/physiology ; *Bipolar Disorder/therapy ; }, abstract = {Knowledge of the microbiome-gut-brain axis has revolutionized the field of psychiatry. It is now well recognized that the gut bacteriome is associated with, and likely influences, the pathogenesis of mental disorders, including major depressive disorder and bipolar disorder. However, while substantial advances in the field of microbiome science have been made, we have likely only scratched the surface in our understanding of how these ecosystems might contribute to mental disorder pathophysiology. Beyond the gut bacteriome, research into lesser explored components of the gut microbiome, including the gut virome, mycobiome, archaeome, and parasitome, is increasingly suggesting relevance in psychiatry. The contribution of microbiomes beyond the gut, including the oral, lung, and small intestinal microbiomes, to human health and pathology should not be overlooked. Increasing both our awareness and understanding of these less traversed fields of research are critical to improving the therapeutic benefits of treatments targeting the gut microbiome, including fecal microbiome transplantation, postbiotics and biogenics, and dietary intervention. Interdisciplinary collaborations integrating systems biology approaches are required to fully elucidate how these different microbial components and distinct microbial niches interact with each other and their human hosts. Excitingly, we may be at the start of the next microbiome revolution and thus one step closer to informing the field of precision psychiatry to improve outcomes for those living with mental illness.}, }
@article {pmid37655340, year = {2023}, author = {Zhang, Q and Zhou, J and Zhang, X and Mao, R and Zhang, C}, title = {Mendelian randomization supports causality between gut microbiota and chronic hepatitis B.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1243811}, pmid = {37655340}, issn = {1664-302X}, abstract = {BACKGROUND: Observational studies have provided evidence of a close association between gut microbiota and the progression of chronic hepatitis B (CHB). However, establishing a causal relationship between gut microbiota and CHB remains a subject of investigation.<br><br>METHODS: Genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of CHB came from the Medical Research Council Integrative Epidemiology Unit (IEU) Open GWAS project. Based on the maximum likelihood (ML), Mendelian randomization (MR)-Egger regression, inverse variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and weighted-mode and weighted-median methods, we conducted a bidirectional, two-sample, MR analysis to explore the causal relationship between the gut microbiota and CHB. Additionally, we evaluated the genetic associations between individual gut microbes and CHB using the Linkage disequilibrium score regression (LDSC) program.<br><br>RESULTS: According to the IVW method estimates, genetically predicted class Alphaproteobacteria (odds ratio [OR]&#x2009;=&#x2009;0.57; 95% confidence interval [CI], 0.34-0.96; false discovery rate [FDR]&#x2009;=&#x2009;0.046), genus Family XIII AD3011 group (OR&#x2009;=&#x2009;0.60; 95% CI, 0.39-0.91; FDR&#x2009;=&#x2009;0.026), genus Prevotella 7 (OR&#x2009;=&#x2009;0.73; 95% CI, 0.56-0.94; FDR&#x2009;=&#x2009;0.022) exhibited a protective effect against CHB. On the other hand, family Family XIII (OR&#x2009;=&#x2009;1.79; 95% CI, 1.03-3.12; FDR&#x2009;=&#x2009;0.061), genus Eggerthella group (OR&#x2009;=&#x2009;1.34; 95% CI, 1.04-1.74; FDR&#x2009;=&#x2009;0.043), genus Eubacterium ventriosum group (OR&#x2009;=&#x2009;1.59; 95% CI, 1.01-2.51; FDR&#x2009;=&#x2009;0.056), genus Holdemania (OR&#x2009;=&#x2009;1.35; 95% CI, 1.00-1.82; FDR&#x2009;=&#x2009;0.049), and genus Ruminococcus gauvreauii group (OR&#x2009;=&#x2009;1.69; 95% CI, 1.10-2.61; FDR&#x2009;=&#x2009;0.076) were associated with an increased risk of CHB. The results from LDSC also indicated a significant genetic correlation between most of the aforementioned gut microbiota and CHB. Our reverse MR analysis demonstrated no causal relationship between genetically predicted CHB and gut microbiota, and we observed no significant horizontal pleiotropy or heterogeneity of instrumental variables (IVs).<br><br>CONCLUSION: In this study, we identified three types of gut microbiota with a protective effect on CHB and five types with an adverse impact on CHB. We postulate that this information will facilitate the clinical prevention and treatment of CHB through fecal microbiota transplantation.}, }
@article {pmid37654676, year = {2023}, author = {Jiang, Y and Cui, W and Zhang, Y and Wang, T and Zheng, X and Li, H and Shang, J}, title = {FG-4592 relieves diabetic kidney disease severity by influencing metabolic profiles via gut microbiota reconstruction in both human and mouse models.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1195441}, pmid = {37654676}, issn = {1664-042X}, abstract = {Objective: Diabetic kidney disease (DKD) is one of the most prevalent complications of diabetes mellitus (DM) and is highly associated with devastating outcomes. Hypoxia-inducible factor (HIF), the main transcription factor that regulates cellular responses to hypoxia, plays an important role in regulating erythropoietin (EPO) synthesis. FG-4592 is the HIF stabilizer that is widely used in patients with renal anemia. We investigated the effect of FG-4592 on DKD phenotypes and the pharmacologic mechanism from the perspective of gut microbiota and systemic metabolism. Design: We collected the clinical data of 73 participants, including 40 DKD patients with combined renal anemia treated with FG-4592, and 33 clinical index-matched DKD patients without FG-4592 treatment from The First Affiliated Hospital of Zhengzhou University at the beginning and after a 3-6-month follow-up period. We established DKD mouse models treated by FG-4592 and performed fecal microbiota transplantation from FG-4592-treated DKD mice to investigate the effects of FG-4592 on DKD and to understand this mechanism from a microbial perspective. Untargeted metabolome-microbiome combined analysis was implemented to globally delineate the mechanism of FG-4592 from both microbial and metabolomic aspects. Result: DKD phenotypes significantly improved after 3-6 months of FG-4592 treatment in DKD patients combined with renal anemia, including a decreased level of systolic blood pressure, serum creatinine, and increased estimated glomerular infiltration rate. Such effects were also achieved in the DKD mouse model treated with FG-4592 and can be also induced by FG-4592-influenced gut microbiota. Untargeted plasma metabolomics-gut microbiota analysis showed that FG-4592 dramatically altered both the microbial and metabolic profiles of DKD mice and relieved DKD phenotypes via upregulating beneficial gut microbiota-associated metabolites. Conclusion: FG-4592 can globally relieve the symptoms of DKD patients combined with renal anemia. In the animal experiment, FG-4592 can reconstruct the intestinal microbial profiles of DKD to further upregulate the production of gut-associated beneficial metabolites, subsequently improving DKD phenotypes.}, }
@article {pmid37654670, year = {2023}, author = {Malard, F and Loschi, M and Huynh, A and Cluzeau, T and Guenounou, S and Legrand, F and Magro, L and Orvain, C and Charbonnier, A and Panz-Klapuch, M and Desmier, D and Mear, JB and Cornillon, J and Robin, C and Daguindau, E and Bilger, K and Vehreschild, MJGT and Chevallier, P and Labussière-Wallet, H and Mediavilla, C and Couturier, MA and Bulabois, CE and Camus, V and Chantepie, S and Ceballos, P and Gaugler, B and Holler, E and Doré, J and Prestat, E and Gasc, C and Plantamura, E and Mohty, M}, title = {Pooled allogeneic faecal microbiota MaaT013 for steroid-resistant gastrointestinal acute graft-versus-host disease: a single-arm, multicentre phase 2 trial.}, journal = {EClinicalMedicine}, volume = {62}, number = {}, pages = {102111}, pmid = {37654670}, issn = {2589-5370}, abstract = {BACKGROUND: Failure of gastrointestinal acute graft-versus-host disease (GI-aGvHD) to respond to steroid therapy is associated with limited further therapeutic options. We aimed to assess the safety and efficacy of the first-in-human use of the pooled allogeneic faecal microbiota, MaaT013, for the treatment of steroid-refractory GI-aGvHD.<br><br>METHODS: This prospective, international, single-arm, phase 2a study reports clinical outcomes from a 24-patient cohort with grade III-IV, steroid refractory GI-aGvHD treated with the pooled allogeneic faecal microbiota MaaT013. MaaT013 involved pooling faecal matter from 3 to 8 screened donors then transplanting the pooled batches into patients to treat GI-aGVHD. The 24 patients were treated in the HERACLES study (Aug 2018 to Nov 2020) at 26 sites in Europe and an additional 52 patients were treated in a compassionate use/expanded access program (EAP) in France (July 2018 to April 2021). The primary endpoint was GI response at day 28, defined as the proportion of patients with GI-aGvHD who had a complete response (CR) or very good partial response (VGPR). GvHD grading and staging were assessed according to the revised Glucksberg criteria. Adverse events and severe adverse events were monitored for 6 months and 12 months, respectively. The HERACLES study was registered with ClinicalTrials.gov (NCT03359980).<br><br>FINDINGS: Compared with single donors, MaaT013 is characterised by higher microbial richness and reduced variability across batches. At day 28 (D28), the GI-overall response rate (ORR) was 38% in the prospective population, including 5 complete responses (CR), 2 very good partial responses (VGPR) and 2 partial responses (PR). In the EAP, the GI-ORR was 58% (17 CR, 9 VGPR and 4&#xa0;PR). The 12-month overall survival (OS) was 25% in the prospective study and 38% in the EAP. Regarding safety, five infectious complications, including 3 sepsis, could not be excluded from being related to the study procedure in HERACLES. Shotgun sequencing analyses of the identified strains suggest that none were found in MaaT013. In the EAP, 18 pharmacovigilance cases were reported among 52 treated patients, including 11 bacteraemia/sepsis. In HERACLES, we observed in stools from responding patients at D28 a higher microbiota richness and increased levels of beneficial bacteria, in particular butyrate producers, along with increased levels of short-chain fatty acid and bile acids. In contrast, stools from non-responding (NR) patients displayed increased levels of pathogenic pro-inflammatory bacteria along with increased systemic inflammatory parameters.<br><br>INTERPRETATION: Overall, MaaT013 was safe in this population of highly immunocompromised patients and was associated with responses in some patients with GI-aGvHD and deserves further investigation.<br><br>FUNDING: MaaT Pharma.}, }
@article {pmid37652953, year = {2023}, author = {Wu, J and Li, C and Gao, P and Zhang, C and Zhang, P and Zhang, L and Dai, C and Zhang, K and Shi, B and Liu, M and Zheng, J and Pan, B and Chen, Z and Zhang, C and Liao, W and Pan, W and Fang, W and Chen, C}, title = {Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {326}, pmid = {37652953}, issn = {2059-3635}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Prospective Studies ; *Lung Transplantation ; Cytokines ; Allografts ; }, abstract = {Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.}, }
@article {pmid37648006, year = {2023}, author = {Li, X and Fu, B and Zhao, C and Hu, J and Zhang, X and Fu, Y and She, X and Gu, C and Cheng, M and Wang, F and Song, X and Dai, J and Yin, J and Fu, Y and Zheng, P and Wu, F and Zhu, Y and Ma, K and Gao, X and Wang, M and Zeng, Q and Cui, B}, title = {Early-life noise exposure causes cognitive impairment in a sex-dependent manner by disrupting homeostasis of the microbiota-gut-brain axis.}, journal = {Brain, behavior, and immunity}, volume = {114}, number = {}, pages = {221-239}, doi = {10.1016/j.bbi.2023.08.021}, pmid = {37648006}, issn = {1090-2139}, mesh = {Male ; Female ; Rats ; Animals ; Brain-Gut Axis ; Neuroinflammatory Diseases ; *Cognitive Dysfunction ; *Gastrointestinal Microbiome/physiology ; Fatty Acids, Volatile/metabolism/pharmacology ; Homeostasis ; }, abstract = {Epidemiological investigations show that noise exposure in early life is associated with health and cognitive impairment. The gut microbiome established in early life plays a crucial role in modulating developmental processes that subsequently affect brain function and behavior. Here, we examined the impact of early-life exposure to noise on cognitive function in adolescent rats by analyzing the gut microbiome and metabolome to elucidate the underlying mechanisms. Chronic noise exposure during early life led to cognitive deficits, hippocampal injury, and neuroinflammation. Early-life noise exposure showed significant difference on the composition and function of the gut microbiome throughout adolescence, subsequently causing axis-series changes in fecal short-chain fatty acid (SCFA) metabolism and serum metabolome profiles, as well as dysregulation of endothelial tight junction proteins, in both intestine and brain. We also observed sex-dependent effects of microbiota depletion on SCFA-related beneficial bacteria in adolescence. Experiments on microbiota transplantation and SCFA supplementation further confirmed the role of intestinal bacteria and related SCFAs in early-life noise-exposure-induced impairments in cognition, epithelial integrity, and neuroinflammation. Overall, these results highlight the homeostatic imbalance of microbiota-gut-brain axis as an important physiological response toward environmental noise during early life and reveals subtle differences in molecular signaling processes between male and female rats.}, }
@article {pmid37647637, year = {2024}, author = {Brothers, AW and Pak, DJ and Poole, NM and Kronman, MP and Bettinger, B and Wilkes, JJ and Carpenter, PA and Englund, JA and Weissman, SJ}, title = {Individualized Antibiotic Plans as a Quality Improvement Initiative to Reduce Carbapenem Use for Hematopoietic Cell Transplant Patients at a Freestanding Pediatric Hospital.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {78}, number = {1}, pages = {15-23}, doi = {10.1093/cid/ciad518}, pmid = {37647637}, issn = {1537-6591}, mesh = {Child ; Humans ; *Anti-Bacterial Agents ; Carbapenems/therapeutic use ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Hospitals, Pediatric ; Quality Improvement ; }, abstract = {BACKGROUND: Providers must balance effective empiric therapy against toxicity risks and collateral damage when selecting antibiotic therapy for patients receiving hematopoietic cell transplant (HCT). Antimicrobial stewardship interventions during HCT are often challenging due to concern for undertreating potential infections.<br><br>METHODS: In an effort to decrease unnecessary carbapenem exposure for patients undergoing HCT at our pediatric center, we implemented individualized antibiotic plans (IAPs) to provide recommendations for preengraftment neutropenia prophylaxis, empiric treatment of febrile neutropenia, and empiric treatment for hemodynamic instability. We compared monthly antibiotic days of therapy (DOT) adjusted per 1000 patient-days for carbapenems, antipseudomonal cephalosporins, and all antibiotics during two 3-year periods immediately before and after the implementation of IAPs to measure the impact of IAP on prescribing behavior. Bloodstream infection (BSIs) and Clostridioides difficile (CD) positivity test rates were also compared between cohorts. Last, providers were surveyed to assess their experience of using IAPs in antibiotic decision making.<br><br>RESULTS: Overall antibiotic use decreased after the implementation of IAPs (monthly reduction of 19.6 DOT/1000 patient-days; P = .004), with carbapenems showing a continuing decline after IAP implementation. BSI and CD positivity rates were unchanged. More than 90% of providers found IAPs to be either extremely or very valuable for their practice.<br><br>CONCLUSIONS: Implementation of IAPs in this high-risk HCT population led to reduction in overall antibiotic use without increase in rate of BSI or CD test positivity. The program was well received by providers.}, }
@article {pmid37646895, year = {2023}, author = {Reasoner, SA and Nicholson, MR}, title = {Clostridioides difficile Infection in Pediatric Inflammatory Bowel Disease.}, journal = {Current gastroenterology reports}, volume = {25}, number = {11}, pages = {316-322}, pmid = {37646895}, issn = {1534-312X}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; T32 GM007347/GM/NIGMS NIH HHS/United States ; T32GM007347/GF/NIH HHS/United States ; K23AI156132/GF/NIH HHS/United States ; }, mesh = {Adult ; Humans ; Child ; *Clostridioides difficile ; *Inflammatory Bowel Diseases/complications/therapy ; *Clostridium Infections/complications/diagnosis/epidemiology ; Fecal Microbiota Transplantation/methods ; Risk Factors ; }, abstract = {PURPOSE OF REVIEW: Children with inflammatory bowel disease (IBD) are at increased risk of C. difficile infection (CDI) and experience worse outcomes associated with an infection. In this article, we review recent research on the incidence, diagnosis, complications, and treatment options for CDI in children with IBD.<br><br>RECENT FINDINGS: Children with IBD have an elevated incidence of CDI, but their CDI risk does not associate with established risk factors in adults with IBD. Existing testing methodologies are inadequate at differentiating CDI from C. difficile colonization in children with IBD. Fecal microbiota transplantation offers a durable cure for recurrent CDI. CDI remains a frequent occurrence in children with IBD. Careful clinical monitoring should be used to diagnose CDI and patients with co-occurring IBD and CDI require careful surveillance for worse outcomes. Future research should explore the optimal diagnosis and treatment modalities in this unique patient population.}, }
@article {pmid37644161, year = {2023}, author = {Koo, H and Morrow, CD}, title = {Identification of donor Bacteroides vulgatus genes encoding proteins that correlate with early colonization following fecal transplant of patients with recurrent Clostridium difficile.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {14112}, pmid = {37644161}, issn = {2045-2322}, mesh = {Child ; Humans ; Animals ; Mice ; *Fecal Microbiota Transplantation ; *Clostridioides difficile/genetics ; Tissue Donors ; Bacteroides/genetics ; }, abstract = {Due to suppressive antibiotics, patients with recurrent Clostridium difficile have gut microbial communities that are devoid of most commensal microbes. Studies have shown that most of the failures using fecal microbe transplantation (FMT) for recurrent C. difficile occur during the first 4 weeks following transplantation. To identify features of donor Bacteroides vulgatus that lead to early colonization, we used two data sets that collected fecal samples from recipients at early times points post FMT. The first analysis used the shotgun metagenomic DNA sequencing data set from Aggarwala et al. consisting of 7 FMT donors and 13 patients with recurrent C. difficile with fecal samples taken as early as 24 h post FMT. We identified 2 FMT donors in which colonization of recipients by donor B. vulgatus was detected as early as 24 h post FMT. We examined a second data set from Hourigan et al. that collected fecal samples from C. difficile infected children and identified 1 of 3 FMT that also had early colonization of the donor B. vulgatus. We found 19 genes out of 4911 encoding proteins were unique to the 3 donors that had early colonization. A gene encoding a putative chitobiase was identified that was in a gene complex that had been previously identified to enhance colonization in mice. A gene encoding a unique fimbrillin (i.e., pili) family protein and 17 genes encoding hypothetical proteins were also specific for early colonizing donors. Most of the genes encoding hypothetical proteins had neighboring genes that encoded proteins involved in mobilization or transposition. Finally, analysis of 42 paired fecal samples from the human microbiome project (HMP) found no individuals had all 19 genes while 2 individuals had none of the 19 genes. Based on the results from our study, consideration should be given to the screening of FMT donors for these B. vulgatus genes found to enhance early colonization that would be of benefit to promote colonization following FMT.}, }
@article {pmid37641627, year = {2023}, author = {Zhang, D and Liu, Z and Bai, F}, title = {Roles of Gut Microbiota in Alcoholic Liver Disease.}, journal = {International journal of general medicine}, volume = {16}, number = {}, pages = {3735-3746}, pmid = {37641627}, issn = {1178-7074}, abstract = {Alcoholic liver disease (ALD)-one of the most common liver diseases - involves a wide range of disorders, including asymptomatic hepatic steatosis, alcoholic hepatitis (AH), liver fibrosis, and cirrhosis. Alcohol consumption induces a weakened gut barrier and changes in the composition of the gut microbiota. The presence of CYP2E1 and its elevated levels in the gastrointestinal tract after alcohol exposure lead to elevated levels of ROS and acetaldehyde, inducing inflammation and oxidative damage in the gut. At the same time, the influx of harmful molecules such as the bacterial endotoxin LPS and peptidogly from gut dysbiosis can induce intestinal inflammation and oxidative damage, further compromising the intestinal mucosal barrier. In this process, various oxidative stress-mediated post-translational modifications (PTMs) play an important role in the integrity of the barrier, eg, the presence of acetaldehyde will result in the sustained phosphorylation of several paracellular proteins (occludin and zona occludens-1), which can lead to intestinal leakage. Eventually, persistent oxidative stress, LPS infiltration and hepatocyte damage through the enterohepatic circulation will lead to hepatic stellate cell activation and hepatic fibrosis. In addition, probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), bioengineered bacteria, gut-restricted FXR agonists and others are promising therapeutic approaches that can alter gut microbiota composition to improve ALD. In the future, there will be new challenges to study the interactions between the genetics of individuals with ALD and their gut microbiome, to provide personalized interventions targeting the gut-liver axis, and to develop better techniques to measure microbial communities and metabolites in the body.}, }
@article {pmid37641043, year = {2023}, author = {Wu, L and Yuan, Q and Wu, L and Hua-Xiang Xia, H and Zhong, M and Liu, T and Ye, X and Luo, D and Xu, J and Xie, W and He, X and Cai, J}, title = {Efficacy of washed microbiota transplantation for therapeutic targets of refractory functional constipation and the influencing factors: a single-center, retrospective, 24-week follow-up study.}, journal = {BMC gastroenterology}, volume = {23}, number = {1}, pages = {291}, pmid = {37641043}, issn = {1471-230X}, support = {2023A04J1850//Science and Technology Program of Guangzhou, China/ ; A2020172//Medical Scientific Research Foundation of Guangdong Province/ ; 20221232//Scientific Research Project of Guangdong Provincial Bureau of traditional Chinese Medicine/ ; 2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; }, mesh = {Humans ; Follow-Up Studies ; Retrospective Studies ; *Constipation/therapy ; Defecation ; *Microbiota ; }, abstract = {BACKGROUND: The efficacy of washed microbiota transplantation (WMT) in terms of refractory functional constipation (FC)-related therapeutic targets and influencing factors have not been elucidated. This study aimed to assess the efficacy and influencing factors of WMT in treating refractory FC-related therapeutic targets.<br><br>METHODS: The clinical data of patients diagnosed with refractory FC and received with WMT were retrospectively collected. The therapeutic targets included straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, manual maneuvers, and decreased stool frequency. Each target was recorded as 1 (yes) or 0 (no). All patients were followed up for approximately 24 weeks from the end of the first course of WMT. The primary outcomes were the improvement rates for the individual therapeutic targets and the overall response in respect of the therapeutic targets decreased by 2 at weeks 4, 8, and 24. The secondary outcomes were the clinical remission rate (i.e., the proportion of patients with an average of 3 or more spontaneous complete bowel movements per week), clinical improvement rate (i.e., the proportion of patients with an average increase of 1 or more SCBMs/week or patients with remission), stool frequency, Wexner constipation score, Bristol Stool Form Scale (BSFS) score, and adverse events. The factors influencing the efficacy were also analyzed.<br><br>RESULTS: Overall, 63 patients with 112 WMT courses were enrolled. The improvement rates at weeks 8 and 24 were 45.6% and 35.0%, 42.9% and 38.6%, 45.0% and 35.7%, 55.6% and 44.4%, and 60.9% and 50.0%, respectively, for straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, and decreased stool frequency. The overall response rates were 49.2%, 50.8%, and 42.9%, respectively, at weeks 4, 8, and 24. The rates of clinical remission and clinical improvement were 54.0% and 68.3%, respectively, at weeks 4. The stool frequency, BSFS score, and Wexner constipation score tended to improve post-WMT. Only 22 mild adverse events were observed during the 112 WMT courses and the follow-up. The number of WMT courses was identified to be the independent factor influencing the efficacy.<br><br>CONCLUSIONS: WMT is efficacious in improving refractory FC-related therapeutic targets. The effectiveness of WMT in the management of FC is enhanced with the administration of multiple courses.}, }
@article {pmid37640503, year = {2023}, author = {Muino, AF and Compo, NR and Everett, BM and Abrahams, DF and Baldwin, MK and James, TN and Wanner, SE and Perkins, MJ and Parr, CE and Wiltshire, ND and Miedel, EL and Engelman, RW}, title = {Equipment and Methods for Concurrently Housing Germfree and Gnotobiotic Mice in the Same Room.}, journal = {Journal of the American Association for Laboratory Animal Science : JAALAS}, volume = {62}, number = {5}, pages = {395-408}, pmid = {37640503}, issn = {2769-6677}, mesh = {Mice ; Animals ; *Germ-Free Life ; *Microbiota ; Housing, Animal ; Sterilization ; Hydrogen Peroxide ; }, abstract = {Here, we combined the use of 2 technologies that have not previously been used together-a positively pressurized isolator IVC (IsoIVC-P) and a modular isolator with integrated vaporized hydrogen peroxide (VHP) technology???to develop highly tractable and scalable methods to support long-term maintenance of germfree mouse colonies and the concurrent use of germfree and gnotobiotic mice in the same room. This space-efficient system increases the practicality of microbiome studies. Specifically, the exterior surfaces of microbially similar IsoIVC-P were sterilized by using VHP prior to opening the cages and handling the mice therein. This space-efficient system increases the feasibility of microbiome studies. After over 74 wk of experimentation and handling equivalent to more than 1,379,693 germfree mouse-days, we determined that the method and practices we developed have a weekly performance metric of 0.0001 sterility breaks per husbandry unit; this rate is comparable to the isolator 'gold standard.' These data were achieved without adverse incidents while maintaining an Altered Schaedler Flora colony and multiple gnotobiotic studies involving fecal microbial transplants in the same room. Our novel IsoIVC-P???VHP workstation housing system thus improves microbiome research efficiency, eliminates hazards, and reduces risks associated with traditional methods.}, }
@article {pmid37640378, year = {2023}, author = {Hwang, SW and Kim, MK and Kweon, MN}, title = {Gut microbiome on immune checkpoint inhibitor therapy and consequent immune-related colitis: a review.}, journal = {Intestinal research}, volume = {21}, number = {4}, pages = {433-442}, pmid = {37640378}, issn = {1598-9100}, support = {2022IP0079//Asan Institute for Life Sciences, Asan Medical Center/ ; 2023IP0058//Asan Institute for Life Sciences, Asan Medical Center/ ; }, abstract = {Immune checkpoint inhibitors have dramatically revolutionized the therapeutic landscape for patients with advanced malignancies. Recently, convincing evidence has shown meaningful influence of gut microbiome on human immune system. With the complex link between gut microbiome, host immunity and cancer, the variations in the gut microbiota may influence the efficacy of immune checkpoint inhibitors. Indeed, some bacterial species have been reported to be predictive for cancer outcome in patients treated with immune checkpoint inhibitors. Although immune checkpoint inhibitors are currently proven to be an effective anti-tumor treatment, they can induce a distinct form of toxicity, termed immune-related adverse events. Immune-related colitis is one of the common toxicities from immune checkpoint inhibitors, and it might preclude the cancer therapy in severe or refractory cases. The manipulation of gut microbiome by fecal microbiota transplantation or probiotics administration has been suggested as one of the methods to enhance anti-tumor effects and decrease the risk of immune-related colitis. Here we review the role of gut microbiome on immune checkpoint inhibitor therapy and consequent immune-related colitis to provide a new insight for better anti-cancer therapy.}, }
@article {pmid37639247, year = {2023}, author = {Bretthauer, M and Wieszczy, P and Løberg, M and Kaminski, MF and Werner, TF and Helsingen, LM and Mori, Y and Holme, &#xd8; and Adami, HO and Kalager, M}, title = {Estimated Lifetime Gained With Cancer Screening Tests: A Meta-Analysis of Randomized Clinical Trials.}, journal = {JAMA internal medicine}, volume = {183}, number = {11}, pages = {1196-1203}, pmid = {37639247}, issn = {2168-6114}, mesh = {Male ; Humans ; Early Detection of Cancer ; Prostate-Specific Antigen ; Mass Screening/methods ; *Prostatic Neoplasms/diagnosis ; *Lung Neoplasms ; Randomized Controlled Trials as Topic ; *Colorectal Neoplasms ; Colonoscopy ; Occult Blood ; }, abstract = {IMPORTANCE: Cancer screening tests are promoted to save life by increasing longevity, but it is unknown whether people will live longer with commonly used cancer screening tests.<br><br>OBJECTIVE: To estimate lifetime gained with cancer screening.<br><br>DATA SOURCES: A systematic review and meta-analysis was conducted of randomized clinical trials with more than 9 years of follow-up reporting all-cause mortality and estimated lifetime gained for 6 commonly used cancer screening tests, comparing screening with no screening. The analysis included the general population. MEDLINE and the Cochrane library databases were searched, and the last search was performed October 12, 2022.<br><br>STUDY SELECTION: Mammography screening for breast cancer; colonoscopy, sigmoidoscopy, or fecal occult blood testing (FOBT) for colorectal cancer; computed tomography screening for lung cancer in smokers and former smokers; or prostate-specific antigen testing for prostate cancer.<br><br>DATA EXTRACTION AND SYNTHESIS: Searches and selection criteria followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Data were independently extracted by a single observer, and pooled analysis of clinical trials was used for analyses.<br><br>MAIN OUTCOMES AND MEASURES: Life-years gained by screening was calculated as the difference in observed lifetime in the screening vs the no screening groups and computed absolute lifetime gained in days with 95% CIs for each screening test from meta-analyses or single randomized clinical trials.<br><br>RESULTS: In total, 2&#x202f;111&#x202f;958 individuals enrolled in randomized clinical trials comparing screening with no screening using 6 different tests were eligible. Median follow-up was 10 years for computed tomography, prostate-specific antigen testing, and colonoscopy; 13 years for mammography; and 15 years for sigmoidoscopy and FOBT. The only screening test with a significant lifetime gain was sigmoidoscopy (110 days; 95% CI, 0-274 days). There was no significant difference following mammography (0 days: 95% CI, -190 to 237 days), prostate cancer screening (37 days; 95% CI, -37 to 73 days), colonoscopy (37 days; 95% CI, -146 to 146 days), FOBT screening every year or every other year (0 days; 95% CI, -70.7 to 70.7 days), and lung cancer screening (107 days; 95% CI, -286 days to 430 days).<br><br>CONCLUSIONS AND RELEVANCE: The findings of this meta-analysis suggest that current evidence does not substantiate the claim that common cancer screening tests save lives by extending lifetime, except possibly for colorectal cancer screening with sigmoidoscopy.}, }
@article {pmid37637989, year = {2023}, author = {Contarino, MF and van Hilten, JJ and Kuijper, EJ}, title = {Targeting the Gut-Brain Axis with Fecal Microbiota Transplantation: Considerations on a Potential Novel Treatment for Parkinson's Disease.}, journal = {Movement disorders clinical practice}, volume = {10}, number = {Suppl 2}, pages = {S21-S25}, pmid = {37637989}, issn = {2330-1619}, }
@article {pmid37637623, year = {2023}, author = {Ratna, HVK and Jeyaraman, M and Yadav, S and Jeyaraman, N and Nallakumarasamy, A}, title = {Is Dysbiotic Gut the Cause of Low Back Pain?.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42496}, pmid = {37637623}, issn = {2168-8184}, abstract = {Low back pain (LBP) is the foremost cause of disability that affects the day-to-day activities of millions of people worldwide. The putative trigger of LBP is linked to the gut microbiome (GM) and its dysbiotic environment. With the concept of GM, various disease pathogenesis has been revisited with plausible crosstalks and micromolecular mimicry. In the normal intervertebral disc (IVD), Firmicutes and Actinobacteria were found in abundance. The blood-disc barrier protects IVD from systemic infection, resists inflammation, and halts the immune surveillance of the inner aspects of IVD. The insights into microbial ecology will broaden our horizons in GM and IVD degeneration in LBP cases. However, an improved understanding of GM and back pain has to be explored in large-scale individuals with varied timescales to validate the above findings. The role of GM (diet, prebiotics, probiotics, and fecal microbiota transplantation) in pain modulation can form novel therapies in cases of LBP.}, }
@article {pmid37636278, year = {2023}, author = {Yin, J and Li, Y and Tian, Y and Zhou, F and Ma, J and Xia, S and Yang, T and Ma, L and Zeng, Q and Liu, G and Yin, Y and Huang, X}, title = {Obese Ningxiang pig-derived microbiota rewires carnitine metabolism to promote muscle fatty acid deposition in lean DLY pigs.}, journal = {Innovation (Cambridge (Mass.))}, volume = {4}, number = {5}, pages = {100486}, pmid = {37636278}, issn = {2666-6758}, abstract = {The gut microbiota consistently shows strong correlations with lipid metabolism in humans and animals, and whether the gut microbiota contributes to muscle fatty acid (FA) deposition and meat traits in farm animals has not been fully resolved. In this study, we aimed to unveil the microbial mechanisms underlying muscle FA deposition in pigs. First, we systematically revealed the correlation between the gut microbiome and muscle FA levels in 43 obese Ningxiang pigs and 50 lean Duroc Landrace Yorkshire (DLY) pigs. Mutual fecal microbial transplantation showed that the obese Ningxiang pig-derived microbiota increased the muscle FA content and improved meat quality by reshaping the gut microbial composition in lean DLY pigs. Lactobacillus reuteri has been identified as a potential microbial biomarker in obese Ningxiang pig-derived microbiota-challenged DLY pigs. A gavage experiment using lean DLY pigs confirmed that L. reuteri XL0930 isolated from obese Ningxiang pigs was the causal species that increased the muscle FA content. Mechanistically, SLC22A5, a carnitine transporter, was downregulated in L. reuteri XL0930-fed DLY pigs, resulting in reduced muscle carnitine levels. Muscle and intestinal L-carnitine levels, which correlated with the muscle FA content, impeded fat synthesis and FA accumulation in in vitro and in vivo models. In conclusion, we uncovered an unexpected and important role of the obese Ningxiang pig-derived microbiota in regulating muscle FA metabolism via the SLC22A5-mediated carnitine system.}, }
@article {pmid37630824, year = {2023}, author = {Yang, JC and Troutman, R and Buri, H and Gutta, A and Situ, J and Aja, E and Jacobs, JP}, title = {Ileal Dysbiosis Is Associated with Increased Acoustic Startle in the 22q11.2 Microdeletion Mouse Model of Schizophrenia.}, journal = {Nutrients}, volume = {15}, number = {16}, pages = {}, pmid = {37630824}, issn = {2072-6643}, support = {IK2 CX001717/CX/CSRD VA/United States ; NA//University of California Los Angeles/ ; }, mesh = {*Chromosomes, Human, Pair 22 ; Disease Models, Animal ; *Chromosome Deletion ; *Schizophrenia/complications/genetics ; *Dysbiosis/complications/genetics ; *Gastrointestinal Microbiome ; Ileum/microbiology ; Reflex, Startle ; *Acoustics ; Humans ; Animals ; Mice ; Mice, Inbred C57BL ; }, abstract = {Recent studies involving transplantation of feces from schizophrenia (SCZ) patients and their healthy controls into germ-free mice have demonstrated that the gut microbiome plays a critical role in mediating SCZ-linked physiology and behavior. To date, only one animal model (a metabotropic glutamate receptor 5 knockout) of SCZ has been reported to recapitulate SCZ-linked gut dysbiosis. Since human 22q11.2 microdeletion syndrome is associated with increased risk of SCZ, we investigated whether the 22q11.2 microdeletion ("Q22") mouse model of SCZ exhibits both SCZ-linked behaviors and intestinal dysbiosis. We demonstrated that Q22 mice display increased acoustic startle response and ileal (but not colonic) dysbiosis, which may be due to the role of the ileum as an intestinal region with high immune and neuroimmune activity. We additionally identified a negative correlation between the abundance of a Streptococcus species in the ilea of Q22 mice and their acoustic startle response, providing early evidence of a gut-brain relationship in these mice. Given the translational relevance of this mouse model, our work suggests that Q22 mice could have considerable utility in preclinical research probing the relationship between gut dysbiosis and the gut-brain axis in the pathogenesis of SCZ.}, }
@article {pmid37630649, year = {2023}, author = {Salmeri, N and Sinagra, E and Dolci, C and Buzzaccarini, G and Sozzi, G and Sutera, M and Candiani, M and Ungaro, F and Massimino, L and Danese, S and Mandarino, FV}, title = {Microbiota in Irritable Bowel Syndrome and Endometriosis: Birds of a Feather Flock Together-A Review.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630649}, issn = {2076-2607}, abstract = {Endometriosis and irritable bowel syndrome (IBS) are chronic conditions affecting up to 10% of the global population, imposing significant burdens on healthcare systems and patient quality of life. Interestingly, around 20% of endometriosis patients also present with symptoms indicative of IBS. The pathogenesis of both these multifactorial conditions remains to be fully elucidated, but connections to gut microbiota are becoming more apparent. Emerging research underscores significant differences in the gut microbiota composition between healthy individuals and those suffering from either endometriosis or IBS. Intestinal dysbiosis appears pivotal in both conditions, exerting an influence via similar mechanisms. It impacts intestinal permeability, triggers inflammatory reactions, and initiates immune responses. Furthermore, it is entwined in a bidirectional relationship with the brain, as part of the gut-brain axis, whereby dysbiosis influences and is influenced by mental health and pain perception. Recent years have witnessed the development of microbiota-focused therapies, such as low FODMAP diets, prebiotics, probiotics, antibiotics, and fecal microbiota transplantation, designed to tackle dysbiosis and relieve symptoms. While promising, these treatments present inconsistent data, highlighting the need for further research. This review explores the evidence of gut dysbiosis in IBS and endometriosis, underscoring the similar role of microbiota in both conditions. A deeper understanding of this common mechanism may enable enhanced diagnostics and therapeutic advancements.}, }
@article {pmid37630643, year = {2023}, author = {Kappéter, &#xc1; and Sipos, D and Varga, A and Vigvári, S and Halda-Kiss, B and Péterfi, Z}, title = {Migraine as a Disease Associated with Dysbiosis and Possible Therapy with Fecal Microbiota Transplantation.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630643}, issn = {2076-2607}, abstract = {Migraine is a painful neurological condition characterized by severe pain on one or both sides of the head. It may be linked to changes in the gut microbiota, which are influenced by antibiotic use and other factors. Dysbiosis, which develops and persists as a result of earlier antibiotic therapy, changes the composition of the intestinal flora, and can lead to the development of various diseases such as metabolic disorders, obesity, hematological malignancies, neurological or behavioral disorders, and migraine. Metabolites produced by the gut microbiome have been shown to influence the gut-brain axis. The use of probiotics as a dietary supplement may reduce the number and severity of migraine episodes. Dietary strategies can affect the course of migraines and are a valuable tool for improving migraine management. With fecal microbiota transplantation, gut microbial restoration is more effective and more durable. Changes after fecal microbiota transplantation were studied in detail, and many data help us to interpret the successful interventions. The microbiological alteration of the gut microflora can lead to normalization of the inflammatory mediators, the serotonin pathway, and influence the frequency and intensity of migraine pain.}, }
@article {pmid37630549, year = {2023}, author = {Munley, JA and Kirkpatrick, SL and Gillies, GS and Bible, LE and Efron, PA and Nagpal, R and Mohr, AM}, title = {The Intestinal Microbiome after Traumatic Injury.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630549}, issn = {2076-2607}, support = {T32 GM008721/GM/NIGMS NIH HHS/United States ; T32 HL160491/HL/NHLBI NIH HHS/United States ; T32 GM-008721/GM/NIGMS NIH HHS/United States ; }, abstract = {The intestinal microbiome plays a critical role in host immune function and homeostasis. Patients suffering from-as well as models representing-multiple traumatic injuries, isolated organ system trauma, and various severities of traumatic injury have been studied as an area of interest in the dysregulation of immune function and systemic inflammation which occur after trauma. These studies also demonstrate changes in gut microbiome diversity and even microbial composition, with a transition to a pathobiome state. In addition, sex has been identified as a biological variable influencing alterations in the microbiome after trauma. Therapeutics such as fecal transplantation have been utilized to ameliorate not only these microbiome changes but may also play a role in recovery postinjury. This review summarizes the alterations in the gut microbiome that occur postinjury, either in isolated injury or multiple injuries, along with proposed mechanisms for these changes and future directions for the field.}, }
@article {pmid37630442, year = {2023}, author = {Ishibashi, R and Matsuhisa, R and Nomoto, M and Chudan, S and Nishikawa, M and Tabuchi, Y and Ikushiro, S and Nagai, Y and Furusawa, Y}, title = {Effect of Oral Administration of Polyethylene Glycol 400 on Gut Microbiota Composition and Diet-Induced Obesity in Mice.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630442}, issn = {2076-2607}, support = {20K05929//JSPS KAKENHI/ ; n/a//Takeda Science Foundation/ ; n/a//Kanamori Foundation/ ; }, abstract = {Polyethylene glycol (PEG) is a commonly used dispersant for oral administration of hydrophobic agents. PEG is partly absorbed in the small intestine, and the unabsorbed fraction reaches the large intestine; thus, oral administration of PEG may impact the gut microbial community. However, to the best of our knowledge, no study evaluated the effects of PEG on gut commensal bacteria. Herein, we aimed to determine whether oral administration of PEG modifies the gut microbiota. Administration of PEG400 and PEG4000 altered gut microbial diversity in a concentration-dependent manner. Taxonomic analysis revealed that Akkermansia muciniphila and particularly Parabacteroides goldsteinii were overrepresented in mice administered with 40% PEG. PEG400 administration ameliorated the high-fat diet (HFD)-induced obesity and adipose tissue inflammation. Fecal microbiome transplantation from PEG400-administered donors counteracted the HFD-induced body and epididymal adipose tissue weight gain, indicating that PEG400-associated bacteria are responsible for the anti-obesity effect. Conversely, carboxymethyl cellulose, also used as a dispersant, did not affect the abundance of these two bacterial species or HFD-induced obesity. In conclusion, we demonstrated that oral administration of a high concentration of PEG400 (40%) alters the gut microbiota composition and ameliorates HFD-induced obesity.}, }
@article {pmid37629716, year = {2023}, author = {Abenavoli, L and Montori, M and Svegliati Baroni, G and Argenziano, ME and Giorgi, F and Scarlata, GGM and Ponziani, F and Scarpellini, E}, title = {Perspective on the Role of Gut Microbiome in the Treatment of Hepatocellular Carcinoma with Immune Checkpoint Inhibitors.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {8}, pages = {}, pmid = {37629716}, issn = {1648-9144}, mesh = {Humans ; *Carcinoma, Hepatocellular/drug therapy ; *Gastrointestinal Microbiome ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Sorafenib ; *Liver Neoplasms/drug therapy ; }, abstract = {Background and Objectives: Hepatocellular carcinoma (HCC) is the leading cause of liver cancer worldwide and has a high mortality rate. Its incidence has increased due to metabolic-associated liver disease (MAFLD) epidemics. Liver transplantation and surgery remain the most resolute measures. Despite the optimistic use of multi-kinase inhibitors, namely sorafenib, the co-existence of chronic liver disease made the response rate low in these patients. Immune checkpoint inhibitors (ICIs) have become a promising hope for certain advanced solid tumors and, also, for advanced HCC. Unfortunately, a large cohort of patients with HCC fail to respond to immunotherapy. Materials and Methods: We conducted a narrative search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: hepatocellular carcinoma, immunotherapy, checkpoint inhibitors, gut microbiota, and fecal microbiota transplantation. Results: ICIs are a promising and sufficiently safe treatment option for HCC. In detail, they have significantly improved survival and prognosis in these patients vs. sorafenib. Although there are several highlighted mechanisms of resistance, the gut microbiota signature can be used both as a response biomarker and as an effect enhancer. Practically, probiotic dose-finding and fecal microbiota transplantation are the weapons that can be used to increase ICI's treatment-response-reducing resistance mechanisms. Conclusion: Immunotherapy has been a significant step-up in HCC treatment, and gut microbiota modulation is an effective liaison to increase its efficacy.}, }
@article {pmid37627687, year = {2023}, author = {MacNair, CR and Tsai, CN and Rutherford, ST and Tan, MW}, title = {Returning to Nature for the Next Generation of Antimicrobial Therapeutics.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {37627687}, issn = {2079-6382}, support = {NA//Genentech/ ; }, abstract = {Antibiotics found in and inspired by nature are life-saving cures for bacterial infections and have enabled modern medicine. However, the rise in resistance necessitates the discovery and development of novel antibiotics and alternative treatment strategies to prevent the return to a pre-antibiotic era. Once again, nature can serve as a source for new therapies in the form of natural product antibiotics and microbiota-based therapies. Screening of soil bacteria, particularly actinomycetes, identified most of the antibiotics used in the clinic today, but the rediscovery of existing molecules prompted a shift away from natural product discovery. Next-generation sequencing technologies and bioinformatics advances have revealed the untapped metabolic potential harbored within the genomes of environmental microbes. In this review, we first highlight current strategies for mining this untapped chemical space, including approaches to activate silent biosynthetic gene clusters and in situ culturing methods. Next, we describe how using live microbes in microbiota-based therapies can simultaneously leverage many of the diverse antimicrobial mechanisms found in nature to treat disease and the impressive efficacy of fecal microbiome transplantation and bacterial consortia on infection. Nature-provided antibiotics are some of the most important drugs in human history, and new technologies and approaches show that nature will continue to offer valuable inspiration for the next generation of antibacterial therapeutics.}, }
@article {pmid37625154, year = {2024}, author = {Gratacós-Ginès, J and Bruguera, P and Pérez-Guasch, M and López-Lazcano, A and Borràs, R and Hernández-Évole, H and Pons-Cabrera, MT and Lligoña, A and Bataller, R and Ginès, P and López-Pelayo, H and Pose, E}, title = {Medications for alcohol use disorder promote abstinence in alcohol-associated cirrhosis: Results from a systematic review and meta-analysis.}, journal = {Hepatology (Baltimore, Md.)}, volume = {79}, number = {2}, pages = {368-379}, doi = {10.1097/HEP.0000000000000570}, pmid = {37625154}, issn = {1527-3350}, mesh = {Humans ; *Alcoholism/complications ; Alcohol Drinking/adverse effects ; Acamprosate/therapeutic use ; Liver Cirrhosis, Alcoholic/drug therapy ; Liver Cirrhosis/drug therapy ; }, abstract = {BACKGROUND AND AIMS: The role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these patients is scarce.<br><br>APPROACH AND RESULTS: We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines on the efficacy of MAUD in patients with cirrhosis. A search was conducted in PubMed, Embase, and Scopus, including all studies until May 2022. The population was defined as patients with AUD and cirrhosis. The primary outcome was alcohol abstinence. Safety was a secondary outcome. We performed a random-effect analysis and expressed the results as relative risk of alcohol consumption. Heterogeneity was measured by I2 . Out of 4095 unique references, 8 studies on 4 different AUD treatments [baclofen (n = 6), metadoxine (n = 1), acamprosate (n = 1), and fecal microbiota transplant (n = 1)] in a total of 794 patients were included. Four were cohort studies, and 4 were RCTs. Only RCTs were included in the meta-analysis. MAUD was associated with a reduced rate of alcohol consumption [relative risk = 0.68 (CI: 0.48-0.97), P = 0.03], increasing alcohol abstinence by 32% compared to placebo or standard treatment, despite high heterogeneity (I2 = 67%). Regarding safety, out of 165 serious adverse events in patients treated with MAUD, only 5 (3%) were possibly or probably related to study medications.<br><br>CONCLUSION: MAUD in patients with cirrhosis is effective in promoting alcohol abstinence and has a good safety profile. Larger studies on the effects of MAUD are needed, especially in patients with advanced liver disease.}, }
@article {pmid37624549, year = {2023}, author = {Pal, P and Shastry, RP}, title = {Exploring the complex role of gut microbiome in the development of precision medicine strategies for targeting microbial imbalance-induced colon cancer.}, journal = {Folia microbiologica}, volume = {68}, number = {5}, pages = {691-701}, pmid = {37624549}, issn = {1874-9356}, support = {ICMR/5/13/84/2020/NCD-III dated 16/03/2021//ICMR-DHR, Government of India, New Delhi/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Precision Medicine/methods ; Dysbiosis/therapy ; *Probiotics/therapeutic use ; *Colonic Neoplasms/therapy ; }, abstract = {The gut microbiome has been increasingly recognized as a key player in the development and progression of colon cancer. Alterations in the gut microbiota, known as dysbiosis, can lead to a variety of medical issues. Microbial adaptation through signals and small molecules can enhance pathogen colonization and modulate host immunity, significantly impacting disease progression. Quorum sensing peptides and molecules have been linked to the progression of colon cancer. Various interventions, such as fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics, have been used to reverse dysbiosis with mixed results and potential side effects. Thus, a personalized approach to treatment selection based on patient characteristics, such as individual gut microbiota manipulation, is necessary to prevent and treat diseases like colon cancer. With advances in metagenomic sequencing and other omics technologies, there has been a growing interest in developing precision medicine strategies for microbial imbalance-induced colon cancer. This review serves as a comprehensive synthesis of current knowledge on the gut microbiome involvement in colon cancer. By exploring the potential of utilizing the gut microbiome as a target for precision medicine, this review underscores the exciting opportunities that lie ahead. Although challenges exist, the integration of microbiome data into precision medicine approaches has the potential to revolutionize the management of colon cancer, providing patients with more personalized and effective treatment options.}, }
@article {pmid37624256, year = {2023}, author = {Mafra, D and Kemp, JA and Borges, NA and Wong, M and Stenvinkel, P}, title = {Gut Microbiota Interventions to Retain Residual Kidney Function.}, journal = {Toxins}, volume = {15}, number = {8}, pages = {}, pmid = {37624256}, issn = {2072-6651}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; Quality of Life ; Fecal Microbiota Transplantation ; Kidney ; }, abstract = {Residual kidney function for patients with chronic kidney disease (CKD) is associated with better quality of life and outcome; thus, strategies should be implemented to preserve kidney function. Among the multiple causes that promote kidney damage, gut dysbiosis due to increased uremic toxin production and endotoxemia need attention. Several strategies have been proposed to modulate the gut microbiota in these patients, and diet has gained increasing attention in recent years since it is the primary driver of gut dysbiosis. In addition, medications and faecal transplantation may be valid strategies. Modifying gut microbiota composition may mitigate chronic kidney damage and preserve residual kidney function. Although various studies have shown the influential role of diet in modulating gut microbiota composition, the effects of this modulation on residual kidney function remain limited. This review discusses the role of gut microbiota metabolism on residual kidney function and vice versa and how we could preserve the residual kidney function by modulating the gut microbiota balance.}, }
@article {pmid37624046, year = {2023}, author = {Ma, C and McCallen, J and McVey, JC and Trehan, R and Bauer, K and Zhang, Q and Ruf, B and Wang, S and Lai, CW and Trinchieri, G and Berzofsky, JA and Korangy, F and Greten, TF}, title = {CSF-1R+ Macrophages Control the Gut Microbiome-Enhanced Liver Invariant NKT Function through IL-18.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {211}, number = {7}, pages = {1099-1107}, pmid = {37624046}, issn = {1550-6606}, support = {ZIA BC011345/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Interleukin-18 ; Vancomycin/pharmacology ; Macrophages ; Liver ; Mice, Knockout ; Receptor Protein-Tyrosine Kinases ; }, abstract = {The gut microbiome is an important modulator of the host immune system. In this study, we found that altering the gut microbiome by oral vancomycin increases liver invariant NKT (iNKT) cell function. Enhanced iNKT cytokine production and activation marker expression were observed in vancomycin-treated mice following both Ag-specific and Ag-independent in vivo iNKT stimulations, with a more prominent effect in the liver than in the spleen. Fecal transplantation studies demonstrated that the iNKT functional regulation is mediated by altering the gut microbiome but uncoupled from the modulation of iNKT cell population size. Interestingly, when stimulated in vitro, iNKT cells from vancomycin-treated mice did not show increased activation, suggesting an indirect regulation. iNKT cells expressed high levels of IL-18 receptor, and vancomycin increased the expression of IL-18 in the liver. Blocking IL-18 by neutralizing Ab or using genetically deficient mice attenuated the enhanced iNKT activation. Liver macrophages were identified as a major source of IL-18. General macrophage depletion by clodronate abolished this iNKT activation. Using anti-CSF-1R depletion or LyzCrexCSF-1RLsL-DTR mice identified CSF-1R+ macrophages as a critical modulator of iNKT function. Vancomycin treatment had no effect on iNKT cell function in vivo in IL-18 knockout macrophage reconstituted mice. Together, our results demonstrate that the gut microbiome controls liver iNKT function via regulating CSF-1R+ macrophages to produce IL-18.}, }
@article {pmid37623261, year = {2023}, author = {Sanekommu, H and Taj, S and Mah Noor, R and Umair Akmal, M and Akhtar, R and Hossain, M and Asif, A}, title = {Probiotics and Fecal Transplant: An Intervention in Delaying Chronic Kidney Disease Progression?.}, journal = {Clinics and practice}, volume = {13}, number = {4}, pages = {881-888}, pmid = {37623261}, issn = {2039-7275}, abstract = {Chronic kidney disease (CKD) is a global health challenge affecting nearly 700 million people worldwide. In the United States alone, the Medicare costs for CKD management has reached nearly USD 80 billion per year. While reversing CKD may be possible in the future, current strategies aim to slow its progression. For the most part, current management strategies have focused on employing Renin Angiotensin Aldosterone (RAS) inhibitors and optimizing blood pressure and diabetes mellitus control. Emerging data are showing that a disruption of the gut-kidney axis has a significant impact on delaying CKD progression. Recent investigations have documented promising results in using microbiota-based interventions to better manage CKD. This review will summarize the current evidence and explore future possibilities on the use of probiotics, prebiotics, synbiotics, and fecal microbial transplant to reduce CKD progression.}, }
@article {pmid37621873, year = {2023}, author = {Fu, X and Tan, H and Huang, L and Chen, W and Ren, X and Chen, D}, title = {Gut microbiota and eye diseases: a bibliometric study and visualization analysis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1225859}, pmid = {37621873}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Graves Ophthalmopathy ; *Diabetic Retinopathy ; Dysbiosis ; Inflammation ; Bibliometrics ; *Macular Degeneration ; }, abstract = {INTRODUCTION: Recently the role of gut microbial dysbiosis in many ocular disorders, including but not limited to uveitis, age-related macular degeneration (AMD), diabetic retinopathy (DR), dry eye, keratitis and orbitopathy is a hot research topic in the field. Targeting gut microbiota to treat these diseases has become an unstoppable trend. Bibliometric study and visualization analysis have become essential methods for literature analysis in the medical research field. We aim to depict this area's research hotspots and future directions by bibliometric software and methods.<br><br>METHODS: We search all the related publications from the Web of Science Core Collection. Then, CiteSpace was applied to analyze and visualize the country distributions, dual-map overlay of journals, keyword bursts, and co-cited references. VOSviewer was employed to identify authors, co-cited authors, journals and co-cited journals and display the keyword co-occurrence networks.<br><br>RESULTS: A total of 284 relevant publications were identified from 2009 to 2023. The number of studies has been small in the first five years and has grown steadily since 2016. These studies were completed by 1,376 authors from 41 countries worldwide, with the United States in the lead. Lin P has published the most papers while Horai R is the most co-cited author. The top journal and co-cited journal are both Investigative Ophthalmology &amp; Visual Science. In the keyword co-occurrence network, except gut microbiota, inflammation becomes the keyword with the highest frequency. Co-citation analyses reveal that gut dysbiosis is involved in common immune- and inflammation-mediated eye diseases, including uveitis, diabetic retinopathy, age-related macular degeneration, dry eye, and Graves' orbitopathy, and the study of microbiomes is no longer limited to the bacterial populations. Therapeutic strategies that target the gut microbiota, such as probiotics, healthy diet patterns, and fecal microbial transplantation, are effective and critical to future research.<br><br>CONCLUSIONS: In conclusion, the bibliometric analysis displays the research hotspots and developmental directions of the involvement of gut microbiota in the pathogenesis and treatment of some ocular diseases. It provides an overview of this field's dynamic evolution and structural relationships.}, }
@article {pmid37621810, year = {2023}, author = {Cheng, X and Li, X and Yang, X and Fang, S and Wang, Z and Liu, T and Zheng, M and Zhai, M and Yang, Z and Shen, T}, title = {Successful Treatment of pMMR MSS IVB Colorectal Cancer Using Anti-VEGF and Anti-PD-1 Therapy in Combination of Gut Microbiota Transplantation: A Case Report.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42347}, pmid = {37621810}, issn = {2168-8184}, abstract = {Immune checkpoint inhibitors (ICI) have shown great promise in treating advanced or metastatic colorectal cancer (mCRC), especially for CRC patients with deficient mismatch repair (dMMR) and high microsatellite instability (MSI-H). For the remainder of CRC patients presenting with proficient mismatch repair (pMMR) and microsatellite stable (MSS) or low microsatellite instability (MSI-L), ICI showed a low-level response. This study describes a 57-year-old Chinese man diagnosed with pMMR MSS IVb CRC with liver metastasis. Primarily, the patient was administered two consecutive treatments, one composed of an anti-EGFR and modified FOLFOX6 and the other composed of an anti-VEGF and FOLFOXIRI. Due to severe chemotherapy side effects, the patient discontinued treatment and decided to take a third investigational treatment, where an anti-PD-1 and an anti-VEGF were given in combination with fecal microbiota transplantation (FMT) capsules. The patient achieved a partial response (PR), and the tumor size decreased to the extent amenable to surgical resection. After surgery, the patient achieved a pathological complete response (pCR). Patients with pMMR MSS or MSI-L hardly benefit from anti-PD-1 immunotherapy. This study indicated that, to a limited extent, FMT might improve the response to ICI for pMMR MSS CRC patients.}, }
@article {pmid37619529, year = {2023}, author = {Sumida, K and Pierre, JF and Yuzefpolskaya, M and Colombo, PC and Demmer, RT and Kovesdy, CP}, title = {Gut Microbiota-Targeted Interventions in the Management of Chronic Kidney Disease.}, journal = {Seminars in nephrology}, volume = {43}, number = {2}, pages = {151408}, pmid = {37619529}, issn = {1558-4488}, support = {R01 DK125586/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/therapy ; *Renal Insufficiency, Chronic/therapy ; *Probiotics/therapeutic use ; *Cardiovascular Diseases ; }, abstract = {Recent advances in microbiome research have informed the potential role of the gut microbiota in the regulation of metabolic, cardiovascular, and renal systems, and, when altered, in the pathogenesis of various cardiometabolic disorders, including chronic kidney disease (CKD). The improved understanding of gut dysbiosis in cardiometabolic pathologies in turn has led to a vigorous quest for developing therapeutic strategies. These therapeutic strategies aim to investigate whether interventions targeting gut dysbiosis can shift the microbiota toward eubiosis and if these shifts, in turn, translate into improvements in (or prevention of) CKD and its related complications, such as premature cardiovascular disease. Existing evidence suggests that multiple interventions (eg, plant-based diets; prebiotic, probiotic, and synbiotic supplementation; constipation treatment; fecal microbiota transplantation; and intestinal dialysis) might result in favorable modulation of the gut microbiota in patients with CKD, and thereby potentially contribute to improving clinical outcomes in these patients. In this review, we summarize the current understanding of the characteristics and roles of the gut microbiota in CKD and discuss the potential of emerging gut microbiota-targeted interventions in the management of CKD.}, }
@article {pmid37615494, year = {2023}, author = {Zhanel, GG and Keynan, R and Keynan, Y and Karlowsky, JA}, title = {The role of Fecal Microbiota Transplantation (FMT) in treating patients with multiple sclerosis.}, journal = {Expert review of neurotherapeutics}, volume = {23}, number = {10}, pages = {921-930}, doi = {10.1080/14737175.2023.2250919}, pmid = {37615494}, issn = {1744-8360}, mesh = {Humans ; Animals ; Mice ; Fecal Microbiota Transplantation/methods ; *Multiple Sclerosis/therapy ; *Gastrointestinal Microbiome ; Inflammation ; Treatment Outcome ; }, abstract = {INTRODUCTION: The associations between multiple sclerosis (MS) and altered intestinal microbiomes have clinicians considering the use of fecal microbiota transplantation (FMT). Animal data suggests that administering FMT from people with MS into healthy mice results in a microbiome with decreased abundance of Sutterella, reduced anti-inflammatory signals, increase in inflammation and experimental autoimmune encephalomyelitis (EAE). Animal studies that administered FMT (from normal healthy donors) into mice resulted in slowing down EAE development relieving symptoms, improving BBB integrity and restoration of microbiota diversity. Human studies indicated clinical benefits of FMT (from healthy donors) in people with MS including: improved intestinal motility and motor ability which lasted at least for the duration of the studies, ranging from 2 to 15 years.<br><br>AREAS COVERED: The authors discuss the efficacy and safety of FMT in treatment of experimental MS in animals and humans with MS. A literature search was performed via PubMed (up to July 2023), using the key words: multiple sclerosis, fecal microbiota transplantation, microbiome.<br><br>EXPERT OPINION: Limited associative data do not provide an understanding of role of FMT in the treatment for MS. Until appropriately designed randomized comparative trials which are underway, are completed, we cannot recommend routine use of FMT in people with MS.}, }
@article {pmid37615438, year = {2023}, author = {Fadlallah, S and Bitar, ER and Hussein, H and Jallad, MA and Matar, GM and Rahal, EA}, title = {The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model.}, journal = {Microbiology spectrum}, volume = {11}, number = {5}, pages = {e0204223}, pmid = {37615438}, issn = {2165-0497}, abstract = {Epstein-Barr virus (EBV) DNA may influence the development of autoimmune diseases by increasing the production of proinflammatory cytokines. Such cytokines have been associated with inducing the dysbiosis of colonic microbiota, which, in turn, is a risk factor for autoimmune diseases such as rheumatoid arthritis (RA). Therefore, we investigated the role that EBV DNA may play in modulating the intestinal microbiota and consequent exacerbation of arthritis in a mouse model. Mice were treated with collagen (arthritis-inducing agent), EBV DNA and collagen, EBV DNA, or water. Fecal samples were collected from arthritic and control mice, and 16S rRNA sequencing was performed to determine the effect of EBV DNA on the composition of colonic microbiota. EBV DNA causes a change in the alpha diversity of the microbiota resulting in an increased Chao1 microbial richness and decreased Shannon diversity index in the RA mouse model. In addition, the abundance of particular genera/genus clusters was significantly altered among the various groups, with the EBV DNA-exacerbated arthritic group having the highest number of altered genera/genus cluster abundances. This group also had the highest number of cells co-expressing IL-17A, FOXP3, and IFNγ in the colons. Antimicrobial-cleared mice transplanted with fecal samples from EBV DNA-exacerbated arthritic mice showed a higher incidence and enhanced severity of RA compared to those transplanted with fecal samples from water or collagen-treated mice. IMPORTANCE Epstein-Barr virus (EBV) DNA alters the composition and diversity of the gut microbiota in a rheumatoid arthritis (RA) mouse model. These induced changes are associated with enhanced severity of symptoms. This better understanding of the various factors involved in the development of RA will possibly help in creating individualized treatments for RA patients including target mediators triggered by viral DNA. Given that a large swathe of the population harbors EBV, a significant proportion of subjects with arthritis may benefit from possible approaches that target EBV or mediators triggered by this virus.}, }
@article {pmid37615344, year = {2023}, author = {Hyde, MK and Masser, BM and Spears, L}, title = {"Why don't you want my poop?" Willing stool donor's experiences of being ineligible to donate intestinal microbiota.}, journal = {Transfusion}, volume = {63}, number = {10}, pages = {1916-1925}, doi = {10.1111/trf.17516}, pmid = {37615344}, issn = {1537-2995}, mesh = {Humans ; *Gastrointestinal Microbiome ; Tissue Donors ; Blood Donors ; Feces ; Emotions ; Motivation ; }, abstract = {BACKGROUND: Blood collection agencies (BCAs) hosting stool (fecal or poo) donor programs report high rates of donor deferral. However, the impact of deferral on willing donors, in terms of personal well-being and future engagement with BCAs, remains unexplored. Accordingly, we surveyed those attempting to donate intestinal microbiota about their experience of being ineligible.<br><br>STUDY DESIGN AND METHODS: A total of 196 potential stool donors from Australia's BCA (>90% blood/blood product donors) completed the first stage of eligibility screening and then an online survey once notified of their ineligibility. Respondents reported motives for donating, perceptions of screening and improvements needed, experience of being told they are ineligible, and their feelings about this.<br><br>RESULTS: Over 80% of participants were ineligible to donate. Of those ineligible, 58% did not know why they were ineligible resulting in potentially future eligible donors being permanently lost. Motives (>5%) included helping others, being a human substance donor, understanding benefits, curiosity/novelty, and helping science/research. Participants identified they needed clear and timely information during screening and a specific reason for their ineligibility. Participants commonly experienced disappointment, confusion, and calm in response to being ineligible.<br><br>DISCUSSION: BCAs need strategies to mitigate the disappointment of ineligible donors, maintain satisfaction with BCAs, and preserve donor identity since many ineligible donors give multiple human substances. BCAs should provide more information about eligibility criteria during early screening stages to reduce disappointment and give personalized information about ineligibility to resolve the confusion. Offering alternative opportunities to give may reduce disappointment and increase ineligible donor engagement.}, }
@article {pmid37615334, year = {2023}, author = {Rajapakse, J and Khatiwada, S and Akon, AC and Yu, KL and Shen, S and Zekry, A}, title = {Unveiling the complex relationship between gut microbiota and liver cancer: opportunities for novel therapeutic interventions.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2240031}, pmid = {37615334}, issn = {1949-0984}, mesh = {Animals ; Humans ; *Liver Neoplasms/therapy ; *Carcinoma, Hepatocellular/therapy ; *Gastrointestinal Microbiome ; Bile Acids and Salts ; }, abstract = {Hepatocellular carcinoma (HCC) has been linked to the gut microbiota, with recent studies revealing the potential of gut-generated responses to influence several arms of the immune responses relevant to HCC formation. The pro- or anti-tumor effects of specific bacterial strains or gut microbiota-related metabolites, such as bile acids and short-chain fatty acids, have been highlighted in many human and animal studies. The critical role of the gut microbiota in HCC development has spurred interest in modulating the gut microbiota through dietary interventions, probiotics, and fecal microbiota transplantation as a potential strategy to improve liver cancer outcomes. Encouragingly, preclinical and clinical studies have demonstrated that modulation of the gut microbiota can ameliorate liver function, reduce inflammation, and inhibit liver tumor growth, underscoring the potential of this approach to improve HCC outcomes. As research continues to unravel the complex and dynamic mechanisms underlying the gut-liver axis, the development of safe and effective interventions to target this pathway for liver cancer prevention and treatment appears to be on the horizon, heralding a significant advance in our ongoing efforts to combat this devastating disease.}, }
@article {pmid37610978, year = {2023}, author = {Koning, M and Herrema, H and Nieuwdorp, M and Meijnikman, AS}, title = {Targeting nonalcoholic fatty liver disease via gut microbiome-centered therapies.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2226922}, pmid = {37610978}, issn = {1949-0984}, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/microbiology ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics ; *Microbiota ; Bacteria/genetics ; Liver/pathology ; }, abstract = {Humans possess abundant amounts of microorganisms, including bacteria, fungi, viruses, and archaea, in their gut. Patients with nonalcoholic fatty liver disease (NAFLD) exhibit alterations in their gut microbiome and an impaired gut barrier function. Preclinical studies emphasize the significance of the gut microbiome in the pathogenesis of NAFLD. In this overview, we explore how adjusting the gut microbiome could serve as an innovative therapeutic strategy for NAFLD. We provide a summary of current information on untargeted techniques such as probiotics and fecal microbiota transplantation, as well as targeted microbiome-focused therapies including engineered bacteria, prebiotics, postbiotics, and phages for the treatment of NAFLD.}, }
@article {pmid37610564, year = {2024}, author = {Arcucci, MS and Menendez, L and Orsi, M and Gallo, J and Guzman, L and Busoni, V and Lifschitz, C}, title = {Role of adjuvant Crohn's disease exclusion diet plus enteral nutrition in asymptomatic pediatric Crohn's disease having biochemical activity: A randomized, pilot study.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {43}, number = {1}, pages = {199-207}, pmid = {37610564}, issn = {0975-0711}, support = {International Cooperation Grant in Child Nutrition of the Spanish Society of Gastroenterology//SEGHNP/ ; Hepatology//SEGHNP/ ; nutrition 2021//SEGHNP/ ; Young Investigator Award of the Latin American Society of Gastroenterology//LASPGHAN/ ; Hepatology//LASPGHAN/ ; Pediatric Nutrition 2022//LASPGHAN/ ; }, mesh = {Humans ; Child ; *Crohn Disease/therapy ; Enteral Nutrition ; Pilot Projects ; Remission Induction ; Diet ; Leukocyte L1 Antigen Complex ; *Biological Products ; }, abstract = {BACKGROUND: Conventional therapy can result in remission in mild-moderate pediatric Crohn's disease (CD). However, some patients experience loss of response to biological drugs despite increased dosage.<br><br>METHODS: We planned to determine that CD exclusion diet plus partial enteral nutrition offers additional benefits in asymptomatic children with CD having elevated fecal calprotectin. A randomized, open-label, pilot, controlled interventional study was conducted in children with CD while on medical treatment and elevated fecal calprotectin on routine testing. Patients continued their medications and were randomized into a group that received CD exclusion diet plus partial enteral nutrition for 12&#xa0;weeks and one that continued a regular diet.<br><br>RESULTS: Twenty-one patients participated: 11 received CD exclusion diet plus partial enteral nutrition and 10, regular diet. Median fecal calprotectin in the CD exclusion diet plus partial enteral nutrition decreased in 9/11 to 50% of baseline, remaining practically unchanged in the regular diet, except for two patients (p&#x2009;=&#x2009;0.005). Body mass index z-score increased in the CD exclusion diet plus partial enteral nutrition. Only 1/11 patients in the CD exclusion diet plus partial enteral nutrition group, while 4/10 in the regular diet, experienced clinical relapse (p&#x2009;=&#x2009;0.149). Only one patient in the CD exclusion diet plus partial enteral nutrition, while eight in the regular diet, were considered to need their biologic treatment intensified (p&#x2009;=&#x2009;0.005); 2/11 in the CD exclusion diet plus partial enteral nutrition had the dose or frequency of the biologic reduced vs. none (0/10) in the regular diet group. The short Pediatric Crohn's Disease Activity Index and anthropometry showed no significant changes in either group.<br><br>CONCLUSIONS: Diet therapy could be a useful addition to medications in children with CD in apparent remission, but elevated fecal calprotectin.<br><br>TRIAL REGISTRATION: Clinical trial number: NCT05034458.}, }
@article {pmid37609255, year = {2023}, author = {Jenior, ML and Leslie, JL and Kolling, GL and Archbald-Pannone, L and Powers, DA and Petri, WA and Papin, JA}, title = {Systems-ecology designed bacterial consortium protects from severe Clostridioides difficile infection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.08.08.552483}, pmid = {37609255}, issn = {2692-8205}, support = {R01 AI124214/AI/NIAID NIH HHS/United States ; R01 AI152477/AI/NIAID NIH HHS/United States ; }, abstract = {Fecal Microbiota Transplant (FMT) is an emerging therapy that has had remarkable success in treatment and prevention of recurrent Clostridioides difficile infection (rCDI). FMT has recently been associated with adverse outcomes such as inadvertent transfer of antimicrobial resistance, necessitating development of more targeted bacteriotherapies. To address this challenge, we developed a novel systems biology pipeline to identify candidate probiotic strains that would be predicted to interrupt C. difficile pathogenesis. Utilizing metagenomic characterization of human FMT donor samples, we identified those metabolic pathways most associated with successful FMTs and reconstructed the metabolism of encoding species to simulate interactions with C. difficile . This analysis resulted in predictions of high levels of cross-feeding for amino acids in species most associated with FMT success. Guided by these in silico models, we assembled consortia of bacteria with increased amino acid cross-feeding which were then validated in vitro . We subsequently tested the consortia in a murine model of CDI, demonstrating total protection from severe CDI through decreased toxin levels, recovered gut microbiota, and increased intestinal eosinophils. These results support the novel framework that amino acid cross-feeding is likely a critical mechanism in the initial resolution of CDI by FMT. Importantly, we conclude that our predictive platform based on predicted and testable metabolic interactions between the microbiota and C. difficile led to a rationally designed biotherapeutic framework that may be extended to other enteric infections.}, }
@article {pmid37606962, year = {2023}, author = {Khanna, S and Voth, E}, title = {Therapeutics for Clostridioides difficile infection: molecules and microbes.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {17}, number = {9}, pages = {903-911}, doi = {10.1080/17474124.2023.2250716}, pmid = {37606962}, issn = {1747-4132}, mesh = {Humans ; Vancomycin/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Fidaxomicin/therapeutic use ; *Clostridioides difficile ; Systematic Reviews as Topic ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation/adverse effects ; Recurrence ; }, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) is a major healthcare problem in the developed world, and effective management of recurrent infection remains one of the biggest challenges. Several advances have occurred in the management of CDI, and in the last 15 years, multiple new agents have been tested. Since 2011, four new products have been approved by the US FDA for treatment of CDI or prevention of recurrent CDI.<br><br>AREAS COVERED: This review focuses on therapeutics of CDI and includes sections on primary prevention, management of active infection, and prevention of recurrent CDI. Specifically, data are included on fecal microbiota transplantation and live biotherapeutics. A comprehensive search of several databases including Ovid MEDLINE(R) and Epub Ahead of Print, In-Process &amp; Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from inception to 1 May 2023 was conducted.<br><br>EXPERT OPINION: Metronidazole is no longer advised for management of outpatient CDI. The preferred medication of choice for a first episode is oral vancomycin or fidaxomicin. For those patients who recur after the first episode, vancomycin taper pulse or fidaxomicin can be used. Intravenous bezlotoxumab, a monoclonal antibody, is available to prevent recurrences. There are now two FDA-approved microbiome-based therapies or live biotherapeutics for prevention of recurrent CDI, for any recurrent CDI and not necessarily multiply recurrent C difficile. Fecal microbiota transplantation remains available in limited settings for recurrent CDI.}, }
@article {pmid37606431, year = {2023}, author = {Jaramillo, AP and Castells, J and Ibrahimli, S and Siegel, S}, title = {Recurrent Multidrug-Resistant Clostridium difficile Infection Secondary to Ulcerative Colitis a Case Report.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {11}, number = {3}, pages = {}, pmid = {37606431}, issn = {2076-3271}, mesh = {Female ; Humans ; *Colitis, Ulcerative/complications/drug therapy ; *Clostridium Infections/complications/drug therapy ; Mesalamine ; Adalimumab ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {IBD consists of two diseases-CD and UC-that affect the digestive tract, with a greater affinity for the large bowel. In this case report, we focus on one of its most common complications. CDI is a pathology that is mostly secondary to UC. Another cause of this bacterial infection is established after the use of antibiotics, most commonly at the hospital level. Around 20 percent of CDI persists because of a chronic dysbiosis of the microbiota and low levels of antibodies against CD toxins. In this case report, we demonstrated mdCDI in a young woman after treatment with multiple drug therapies as well as with semi-invasive procedures as follows: antibiotics (vancomycin, fidaxomicin), anti-inflammatory agents (mesalamine, sulfasalazine), corticosteroids (budesonide, prednisone), integrin receptor antagonists (vedolizumab), several semi-invasive procedures such as fecal transplant microbiota (FMT), aminosalicylates (5-ASA), treatment with tumor necrosis factor (TNF) blockers (adalimumab, golimumab), and immunomodulators (upadcitinib, tofacitinib). This leads us to establish how rCDI and its resistance to different treatments make this a challenge for the health system, both for hospitals and for outpatients, as well as how time-consuming each treatment is from the first intake of the drug until its total efficacy or until patients reach a dose-response and time-response to the disease. Accordingly, this case report and other similar cases reflect the need for randomized control trials or meta-analyses to establish therapeutic guidelines for cases of mdCDI in the near future.}, }
@article {pmid37602197, year = {2023}, author = {Gao, XF and Wu, BB and Pan, YL and Zhou, SM and Zhang, M and You, YH and Cai, YP and Liang, Y}, title = {Gut microbiome biomarkers in adolescent obesity: a regional study.}, journal = {Health information science and systems}, volume = {11}, number = {1}, pages = {37}, pmid = {37602197}, issn = {2047-2501}, abstract = {PURPOSE: This study aimed to characterize the gut microbiota in obese adolescents from Shenzhen (China), and evaluate influence of gender on BMI-related differences in the gut microbiome.<br><br>METHODS: Evaluation of physical examination, blood pressure measurement, serological assay and body composition were conducted in 205 adolescent subjects at Shenzhen. Fecal microbiome composition was profiled via high-throughput sequencing of the V3-V4 regions of the 16S rRNA gene. A Random Forest (RF) classifier model was built to distinguish the BMI categories based on the gut bacterial composition.<br><br>RESULTS: Fifty-six taxa consisting mainly of Firmicutes were identified that having significant associations with BMI; 2 OTUs belonging to Ruminococcaceae and 1 belonging to Lachnospiraceae had relatively strong positive correlations with body fate rate, waistline and most of serum biochemical properties. Based on the 56 BMI-associated OTUs, the RF model showed a robust classification accuracy (AUC 0.96) for predicting the obese phenotype. Gender-specific differences in the gut microbiome composition was obtained, and a lower relative abundance of Odoribacter genus was particularly found in obese boys. Functional analysis revealed a deficiency in bacterial gene contents related to peroxisome and PPAR signaling pathway in the obese subjects for both genders.<br><br>CONCLUSIONS: This study reveals unique features of gut microbiome in terms of microbial composition and metabolic functions in obese adolescents, and provides a baseline for reference and comparison studies.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13755-023-00236-9.}, }
@article {pmid37602044, year = {2023}, author = {Jaramillo, AP and Awosusi, BL and Ayyub, J and Dabhi, KN and Gohil, NV and Tanveer, N and Hussein, S and Pingili, S and Makkena, VK}, title = {Effectiveness of Fecal Microbiota Transplantation Treatment in Patients With Recurrent Clostridium difficile Infection, Ulcerative Colitis, and Crohn's Disease: A Systematic Review.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42120}, pmid = {37602044}, issn = {2168-8184}, abstract = {Cronh's disease and ulcerative colitis (UC) are diseases with unknown etiologies that cause ongoing inflammation in the gastrointestinal system. Chron's disease causes immunological dysregulation, and UC causes intestinal harm due to immune reactions. According to our study, fecal microbiota transplantation (FMT) has many benefits in the treatment of inflammatory bowel disease (IBD) by restoring intestinal homeostasis and reducing clinical symptoms. In mildly symptomatic patients with UC, an FMT treatment combined with an anti-inflammatory diet can produce remission, which would then be followed by a diet that maintained the anti-inflammatory effects. The efficacy of FMT consists of preventing flares or the consequences of IBD. As a result, we must emphasize that more investigation should be done before developing a therapeutic procedure for FMT in IBD and its associated consequences.}, }
@article {pmid37601998, year = {2023}, author = {Edupuganti, S and Yadav, D and Upadhyay, M and Benck, AR and Nika, A}, title = {A Rare Presentation of Myositis and Diffuse Alveolar Hemorrhage Associated With Disseminated Cryptococcus neoformans Infection.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42062}, pmid = {37601998}, issn = {2168-8184}, abstract = {Cryptococcosis is a fungal infection caused by species of the Cryptococcus genus which are commonly found in soil contaminated with bird feces, decaying wood, and tree hollows. It is usually seen in immunocompromised patients such as those with AIDS, with hematological malignancy, on immunosuppressive therapy, or after organ transplantation, and rare in immunocompetent hosts. The primary site of infection is usually the lung and the infection starts after inhalation of the pathogen and depending upon the host's immune response shows a different pattern of infection. Here we present a case report of a female in her late forties, who presented with two weeks of rash in her bilateral upper extremity, lower extremity, chest, and back along with arthralgia, myalgia, and proximal lower extremity weakness. Initial laboratory workup showed leukocytosis, elevated erythrocyte sedimentation rate, C-reactive protein, serum ferritin, and serum aldolase level with normal creatinine kinase. Rheumatological workups including ANA, ANCA, RF, C3, and C4 were normal. Magnetic resonance imaging of the right femur showed hyperintensity of the thigh and proximal calf musculature suggestive of muscle edema. A punch biopsy from the rash showed dyskeratosis with mild perivascular neutrophilic infiltrate. Steroid therapy and rituximab were started with some improvement. However, the patient developed respiratory distress and diffuse alveolar hemorrhage. Bronchoscopy was done and bronchoalveolar lavage fluid grew Serratia and Candida. The patient improved with antibiotic and antifungal therapy. However, the patient again developed respiratory distress and a new diffuse alveolar hemorrhage. A repeat bronchoscopy was done and the new bronchoalveolar lavage grew Cryptococcus neoformans. Blood cultures also grew Cryptococcus neoformans. The patient was started on amphotericin B and flucytosine. The patient initially improved and was transferred to the rehabilitation unit but ultimately her course was complicated by multiple infections and intubations and she unfortunately passed away.}, }
@article {pmid37600604, year = {2023}, author = {Busing, JD and Fouladi, F and Bulik-Sullivan, EC and Carroll, IM and Fodor, AA and Thomsen, KF and Gulati, AS and Nicholson, MR}, title = {Gut Microbial Changes Following Fecal Microbiota Transplantation for D-Lactic Acidosis in Two Children.}, journal = {JPGN reports}, volume = {4}, number = {3}, pages = {e319}, pmid = {37600604}, issn = {2691-171X}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; L30 AI140315/AI/NIAID NIH HHS/United States ; }, abstract = {D-lactic acidosis (D-LA) is an uncommon complication of short bowel syndrome characterized by elevated plasma D-lactate and encephalopathy. Treatments include rehydration, dietary carbohydrate restriction, and antibiotics to alter the gut microbiota. Fecal microbiota transplantation (FMT) has recently been used in children to successfully treat D-LA. We compared the clinical course and then utilized metagenomic shotgun sequencing to describe changes in the composition and function of the intestinal microbiome following FMT in 2 patients with recurrent D-LA. FMT altered the composition of the fecal microbiota in these 2 patients with recurrent D-LA, though not necessarily in a consistent manner. Importantly, microbial metabolic pathways were also impacted by FMT, which may be critical for achieving desired clinical outcomes. While sample size limits the generalizability of our results, these findings set the stage for further understanding of the role of microbes in the pathogenesis of recurrent D-LA.}, }
@article {pmid37599693, year = {2023}, author = {Wang, Y and Ni, Z and Li, J and Shao, Y and Yong, Y and Lv, W and Zhang, S and Fu, T and Chen, A}, title = {Cordyceps cicadae polysaccharides alleviate hyperglycemia by regulating gut microbiota and its mmetabolites in high-fat diet/streptozocin-induced diabetic mice.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1203430}, pmid = {37599693}, issn = {2296-861X}, abstract = {INTRODUCTION: The polysaccharides found in Cordyceps cicadae (C. cicadae) have received increasing academic attention owing to their wide variety of therapeutic activities.<br><br>METHODS: This study evaluated the hypoglycemic, antioxidant, and anti-inflammatory effects of polysaccharides from C. cicadae (CH-P). In addition, 16s rDNA sequencing and untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) were used to estimate the changes and regulatory relationships between gut microbiota and its metabolites. The fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling.<br><br>RESULTS: The results showed that CH-P treatment displayed hypoglycemic, antioxidant, and anti-inflammatory effects and alleviated tissue damage induced by diabetes. The CH-P treatment significantly reduced the Firmicutes/Bacteroidetes ratio and increased the abundance of Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, Mucispirillum, and significantly decreased the abundance of Helicobacter and Lactobacillus compared to the diabetic group. The alterations in the metabolic pathways were mostly related to amino acid biosynthesis and metabolic pathways (particularly those involving tryptophan) according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Correlation analysis showed that Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, and Mucispirillum were positively correlated with indole and its derivatives, such as 5-hydroxyindole-3-acetic acid. Indole intervention significantly improved hyperglycemic symptoms and insulin sensitivity, and increased the secretion of glucagon-like peptide-1 (GLP-1) in diabetic mice. FMT reduced blood glucose levels, improved glucose tolerance, and increased insulin sensitivity in diabetic mice. However, FMT did not significantly improve GLP-1 levels.<br><br>DISCUSSION: This indicates that C. cicadae polysaccharides alleviate hyperglycemia by regulating the production of metabolites other than indole and its derivatives by gut microbiota. This study provides an important reference for the development of novel natural products.}, }
@article {pmid37599322, year = {2023}, author = {Salimi, A and Sepehr, A and Hejazifar, N and Talebi, M and Rohani, M and Pourshafie, MR}, title = {The Anti-Inflammatory Effect of a Probiotic Cocktail in Human Feces Induced-Mouse Model.}, journal = {Inflammation}, volume = {46}, number = {6}, pages = {2178-2192}, pmid = {37599322}, issn = {1573-2576}, mesh = {Humans ; Animals ; Mice ; Feces/microbiology ; *Inflammatory Bowel Diseases/chemically induced/therapy ; Inflammation/chemically induced ; *Probiotics/pharmacology/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; Dextran Sulfate/toxicity ; *Colitis/therapy/drug therapy ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract due to altered interaction between the immune system and the gut microbiota. The aim of this study was to investigate the role of a probiotic cocktail in modulating immune dysregulation induced in mice. Mice were divided into 5 groups (n = 5/group), and inflammation was induced in two separate groups by fecal microbiota transplantation (FMT) from the stool of human with IBD and dextran sulfate sodium (DSS). In the other two groups, the cocktail of Lactobacillus spp. and Bifidobacterium spp. (10[8]CFU/kg/day) was administered daily for a total of 28days in addition to inducing inflammation. A group as a contcxsrol group received only water and food. The alteration of the selected genera of gut microbiota and the expression of some genes involved in the regulation of the inflammatory response were studied in the probiotic-treated and untreated groups by quantitative real-time PCR. The selected genera of gut microbiota of the FMT and DSS groups showed similar patterns on day 28 after each treatment. In the probiotic-treated groups, the population of the selected genera of gut microbiota normalized and the abundance of Firmicutes and Actinobacteria increased compared to the DSS and FMT groups. The expression of genes related to immune response and tight junctions was positively affected by the probiotic. Changes in the gut microbiota could influence the inflammatory status in the gut, and probiotics as a preventive or complementary treatment could improve the well-being of patients with inflammatory bowel disease symptoms.}, }
@article {pmid37596429, year = {2023}, author = {Qiao, CM and Zhou, Y and Quan, W and Ma, XY and Zhao, LP and Shi, Y and Hong, H and Wu, J and Niu, GY and Chen, YN and Zhu, S and Cui, C and Zhao, WJ and Shen, YQ}, title = {Fecal Microbiota Transplantation from Aged Mice Render Recipient Mice Resistant to MPTP-Induced Nigrostriatal Degeneration Via a Neurogenesis-Dependent but Inflammation-Independent Manner.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {20}, number = {5}, pages = {1405-1426}, pmid = {37596429}, issn = {1878-7479}, mesh = {Animals ; Mice ; *Fecal Microbiota Transplantation ; Neuroinflammatory Diseases ; Ki-67 Antigen ; Inflammation ; Dopaminergic Neurons ; Neurogenesis ; *Parkinson Disease ; }, abstract = {Accumulating data support a crucial role of gut microbiota in Parkinson's disease (PD). However, gut microbiota vary with age and, thus, will affect PD in an age-dependent, but unknown manner. We examined the effects of fecal microbiota transplantation (FMT) pretreatment, using fecal microbiota from young (7 weeks) or aged mice (23 months), on MPTP-induced PD model. Motor function, pathological changes, striatal neurotransmitters, neuroinflammation, gut inflammation and gut permeability were examined. Gut microbiota composition and metabolites, namely short-chain fatty acids (SCFAs), were analyzed. Neurogenesis was also evaluated by measuring the number of doublecortin-positive (DCX[+]) neurons and Ki67-positive (Ki67[+]) cells in the hippocampus. Expression of Cd133 mRNA, a cellular stemness marker, in the hippocampus was also examined. Mice who received FMT from young mice showed MPTP-induced motor dysfunction, and reduction of striatal dopamine (DA), dopaminergic neurons and striatal tyrosine hydroxylase (TH) levels. Interestingly and unexpectedly, mice that received FMT from aged mice showed recovery of motor function and rescue of dopaminergic neurons and striatal 5-hydroxytryptamine (5-HT), as well as decreased DA metabolism after MPTP challenge. Further, they showed improved metabolic profiling and a decreased amount of fecal SCFAs. High-throughput sequencing revealed that FMT remarkably reshaped the gut microbiota of recipient mice. For instance, levels of genus Akkermansia and Candidatus Saccharimonas were elevated in fecal samples of recipient mice receiving aged microbiota (AM + MPTP mice) than YM + MPTP mice. Intriguingly, both young microbiota and aged microbiota had no effect on neuroinflammation, gut inflammation or gut permeability. Notably, AM + MPTP mice showed a marked increase in DCX[+] neurons, as well as Ki67[+] cells and Cd133 expression in the hippocampal dentate gyrus (DG) compared to YM + MPTP mice. These results suggest that FMT from aged mice augments neurogenesis, improves motor function and restores dopaminergic neurons and neurotransmitters in PD model mice, possibly through increasing neurogenesis.}, }
@article {pmid37593952, year = {2023}, author = {Koneru, S and Thiruvadi, V and Ramesh, M}, title = {Gut microbiome and its clinical implications: exploring the key players in human health.}, journal = {Current opinion in infectious diseases}, volume = {36}, number = {5}, pages = {353-359}, doi = {10.1097/QCO.0000000000000958}, pmid = {37593952}, issn = {1473-6527}, mesh = {Humans ; *Gastrointestinal Microbiome ; Disease Management ; Fecal Microbiota Transplantation ; *Phage Therapy ; *Probiotics/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: The human gut harbors a diverse community of microorganisms known as the gut microbiota. Extensive research in recent years has shed light on the profound influence of the gut microbiome on human health and disease. This review aims to explore the role of the gut microbiome in various clinical conditions and highlight the emerging therapeutic potential of targeting the gut microbiota for disease management.<br><br>RECENT FINDINGS: Knowledge of the influence of gut microbiota on human physiology led to the development of various therapeutic possibilities such as fecal microbiota transplant (FMT), phage therapy, prebiotics, and probiotics. Recently, the U.S. FDA approved two FMT products for the treatment of recurrent Clostridioides difficile infection with ongoing research for the treatment of various disease conditions.<br><br>SUMMARY: Advancement in the knowledge of the association between gut microbiota and various disease processes has paved the way for novel therapeutics.}, }
@article {pmid37585413, year = {2023}, author = {Li, C and Liu, Y and Liu, X and Bai, X and Jin, X and Xu, F and Chen, H and Zhang, Y and Vallee, I and Liu, M and Yang, Y}, title = {The gut microbiota contributes to changes in the host immune response induced by Trichinella spiralis.}, journal = {PLoS neglected tropical diseases}, volume = {17}, number = {8}, pages = {e0011479}, pmid = {37585413}, issn = {1935-2735}, mesh = {Mice ; Animals ; *Trichinella spiralis ; *Trichinellosis/parasitology ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Immunity ; }, abstract = {The gut microbiota plays an important role in parasite-host interactions and the induction of immune defense responses. Trichinella spiralis is an important zoonotic parasite that can directly or indirectly interact with the host in the gut. Changes in the gut microbiota following infection with T. spiralis and the role of the gut microbiota in host immune defense against T. spiralis infection were investigated in our study. 16S rRNA sequencing analysis revealed that infection with T. spiralis can reduce the diversity of the gut microbiota and alter the structure of the gut microbiota during early infection, which was restored when the worm left the gut. Antibiotic treatment (ABX) and fecal bacterial transplantation (FMT) were used to investigate the role of the gut microbiota in the host expulsion response during infection with T. spiralis. We found that ABX mice had a higher burden of parasites, and the burden of parasites decreased after fecal bacterial transplantation. The results of flow cytometry and qPCR revealed that the disturbance of the gut microbiota affects the proportion of CD4+ T cells and the production of IL-4, which weakens Th2 responses and makes expulsion difficult. In addition, as the inflammatory response decreased with the changes of the microbiota, the Th1 response also decreased. The metabolomic results were in good agreement with these findings, as the levels of inflammatory metabolites such as ceramides were reduced in the ABX group. In general, T. spiralis infection can cause changes in the gut microbiota, and the presence or absence of microbes may also weaken intestinal inflammation and the expulsion of T. spiralis by affecting the immune response of the host.}, }
@article {pmid37583860, year = {2023}, author = {Kriger-Sharabi, O and Malnick, SDH and Fisher, D}, title = {Manipulation of the intestinal microbiome-a slow journey to primetime.}, journal = {World journal of clinical cases}, volume = {11}, number = {21}, pages = {4975-4988}, pmid = {37583860}, issn = {2307-8960}, abstract = {The gut microbiota has important functions in the regulation of normal body functions. Alterations of the microbiota are being increasingly linked to various disease states. The microbiome has been manipulated via the administration of stool from animals or humans, for more than 1000 years. Currently, fecal microbiota transplantation can be performed via endoscopic administration of fecal matter to the duodenum or colon or via capsules of lyophilized stools. More recently fecal microbial transplantation has been shown to be very effective for recurrent Clostridoides difficile infection (CDI). In addition there is some evidence of efficacy in the metabolic syndrome and its hepatic manifestation, metabolic associated fatty liver disease (MAFLD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We review the current literature regarding the microbiome and the pathogenesis and treatment of CDI, MAFLD, IBS and IBD.}, }
@article {pmid37583034, year = {2024}, author = {Bae, GS and Jeon, ES and Son, HC and Kang, P and Lim, KS and Hwang, EH and Kim, G and Baek, SH and An, YJ and Shim, GY and Woo, YM and Kim, Y and Oh, T and Kim, SH and Hong, J and Koo, BS}, title = {Clostridium ventriculi in a cynomolgus monkey with acute gastric dilatation and rupture: A case report.}, journal = {Journal of medical primatology}, volume = {53}, number = {1}, pages = {e12668}, doi = {10.1111/jmp.12668}, pmid = {37583034}, issn = {1600-0684}, support = {//The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021M3H9A2098600)./ ; }, mesh = {Female ; Animals ; Macaca fascicularis ; *Gastric Dilatation/veterinary/pathology ; RNA, Ribosomal, 16S ; *Clostridium ; }, abstract = {Acute gastric dilatation (AGD) is one of the most prevalent and life-threatening diseases in nonhuman primates worldwide. However, the etiology of this syndrome has not been determined. Recently, sudden death occurred in a 7-year-old female cynomolgus monkey with a history of fecal microbiota transplantation using diarrheic stools. The monkey had undergone surgery previously. On necropsy, gastric dilatation and rupture demonstrated a tetrad arrangement on histopathologic examination. On 16S rRNA sequencing, a high population of Clostridium ventriculi was identified in the duodenum adjacent to stomach but not in the colon. This paper is the first report of Clostridium ventriculi infection in a cynomolgus macaque with acute gastric dilatation and rupture.}, }
@article {pmid37581848, year = {2024}, author = {Dou, M and Chu, Y and Zhou, X and Wang, M and Li, X and Ma, R and Fan, Z and Zhao, X and Wang, W and Li, S and Lv, Y and Zhu, L}, title = {Matrine Mediated Immune Protection in MS by Regulating Gut Microbiota and Production of SCFAs.}, journal = {Molecular neurobiology}, volume = {61}, number = {1}, pages = {74-90}, pmid = {37581848}, issn = {1559-1182}, support = {31870334//National Natural Science Foundation of China/ ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Matrines ; RNA, Ribosomal, 16S/genetics ; *Multiple Sclerosis/drug therapy ; *Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Fatty Acids, Volatile ; }, abstract = {There is clearly an unmet need for more effective and safer treatments for multiple sclerosis (MS). Our previous studies showed a significant therapeutic effect of matrine, a monomer of traditional herbal medicine, on experimental autoimmune encephalomyelitis (EAE) mice. To explore the mechanism of matrine action, we used 16S rRNA sequencing technology to determine the gut microbes in matrine-treated EAE mice and controls. The concentrations of short-chain fatty acids (SCFAs) were then tested by metabonomics. Finally, we established pseudo-sterile mice and transplanted into them fecal microbiota, which had been obtained from the high-dose matrine-treated EAE mice to test the effects of matrine. The results showed that matrine could restore the diversity of gut microbiota and promote the production of SCFAs in EAE mice. Transplantation of fecal microbiota from matrine-treated mice significantly alleviated EAE severity, reduced CNS inflammatory infiltration and demyelination, and decreased the level of IL-17 but increased IL-10 in sera of mice. In conclusion, matrine treatment can regulate gut microbiota and metabolites and halt the progression of MS.}, }
@article {pmid37580821, year = {2023}, author = {Shtossel, O and Turjeman, S and Riumin, A and Goldberg, MR and Elizur, A and Bekor, Y and Mor, H and Koren, O and Louzoun, Y}, title = {Recipient-independent, high-accuracy FMT-response prediction and optimization in mice and humans.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {181}, pmid = {37580821}, issn = {2049-2618}, mesh = {Humans ; Animals ; Mice ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Treatment Outcome ; *Microbiota ; }, abstract = {BACKGROUND: Some microbiota compositions are associated with negative outcomes, including among others, obesity, allergies, and the failure to respond to treatment. Microbiota manipulation or supplementation can restore a community associated with a healthy condition. Such interventions are typically probiotics or fecal microbiota transplantation (FMT). FMT donor selection is currently based on donor phenotype, rather than the anticipated microbiota composition in the recipient and associated health benefits. However, the donor and post-transplant recipient conditions differ drastically. We here propose an algorithm to identify ideal donors and predict the expected outcome of FMT based on donor microbiome alone. We also demonstrate how to optimize FMT for different required outcomes.<br><br>RESULTS: We show, using multiple microbiome properties, that donor and post-transplant recipient microbiota differ widely and propose a tool to predict the recipient post-transplant condition (engraftment success and clinical outcome), using only the donors' microbiome and, when available, demographics for transplantations from humans to either mice or other humans (with or without antibiotic pre-treatment). We validated the predictor using a de novo FMT experiment highlighting the possibility of choosing transplants that optimize an array of required goals. We then extend the method to characterize a best-planned transplant (bacterial cocktail) by combining the predictor and a generative genetic algorithm (GA). We further show that a limited number of taxa is enough for an FMT to produce a desired microbiome or phenotype.<br><br>CONCLUSIONS: Off-the-shelf FMT requires recipient-independent optimized FMT selection. Such a transplant can be from an optimal donor or from a cultured set of microbes. We have here shown the feasibility of both types of manipulations in mouse and human recipients. Video Abstract.}, }
@article {pmid37579688, year = {2023}, author = {Liu, Y and Zhou, Q and Ye, F and Yang, C and Jiang, H}, title = {Gut microbiota-derived short-chain fatty acids promote prostate cancer progression via inducing cancer cell autophagy and M2 macrophage polarization.}, journal = {Neoplasia (New York, N.Y.)}, volume = {43}, number = {}, pages = {100928}, pmid = {37579688}, issn = {1476-5586}, mesh = {*Gastrointestinal Microbiome ; *Fatty Acids, Volatile/metabolism ; Disease Progression ; *Autophagy ; *Macrophages/pathology ; Cell Polarity ; *Ruminococcus/metabolism ; *Prostatic Neoplasms, Castration-Resistant/microbiology/pathology ; Mice, Transgenic ; *Bacteroidetes/metabolism ; *Veillonellaceae/metabolism ; Fecal Microbiota Transplantation ; Humans ; Male ; Animals ; Mice ; }, abstract = {We have previously demonstrated abnormal gut microbial composition in castration-resistant prostate cancer (CRPC) patients, here we revealed the mechanism of gut microbiota-derived short-chain fatty acids (SCFAs) as a mediator linking CRPC microbiota dysbiosis and prostate cancer (PCa) progression. By using transgenic TRAMP mouse model, PCa patient samples, in vitro PCa cell transwell and macrophage recruitment assays, we examined the effects of CRPC fecal microbiota transplantation (FMT) and SCFAs on PCa progression. Our results showed that FMT with CRPC patients' fecal suspension increased SCFAs-producing gut microbiotas such as Ruminococcus, Alistipes, Phascolarctobaterium in TRAMP mice, and correspondingly raised their gut SCFAs (acetate and butyrate) levels. CRPC FMT or SCFAs supplementation significantly accelerated mice's PCa progression. In vitro, SCFAs enhanced PCa cells migration and invasion by inducing TLR3-triggered autophagy that further activated NF-κB and MAPK signalings. Meanwhile, autophagy of PCa cells released higher level of chemokine CCL20 that could reprogramme the tumor microenvironment by recruiting more macrophage infiltration and simultaneously polarizing them into M2 type, which in turn further strengthened PCa cells invasiveness. Finally in a cohort of 362 PCa patients, we demonstrated that CCL20 expression in prostate tissue was positively correlated with Gleason grade, pre-operative PSA, neural/seminal vesical invasion, and was negatively correlated with post-operative biochemical recurrence-free survival. Collectively, CRPC gut microbiota-derived SCFAs promoted PCa progression via inducing cancer cell autophagy and M2 macrophage polarization. CCL20 could become a biomarker for prediction of prognosis in PCa patients. Intervention of SCFAs-producing microbiotas may be a useful strategy in manipulation of CRPC.}, }
@article {pmid37577219, year = {2023}, author = {Tan, N and Lubel, J and Kemp, W and Roberts, S and Majeed, A}, title = {Current Therapeutics in Primary Sclerosing Cholangitis.}, journal = {Journal of clinical and translational hepatology}, volume = {11}, number = {5}, pages = {1267-1281}, pmid = {37577219}, issn = {2310-8819}, abstract = {Primary sclerosing cholangitis (PSC) is an orphan, cholestatic liver disease that is characterized by inflammatory biliary strictures with variable progression to end-stage liver disease. Its pathophysiology is poorly understood. Chronic biliary inflammation is likely driven by immune dysregulation, gut dysbiosis, and environmental exposures resulting in gut-liver crosstalk and bile acid metabolism disturbances. There is no proven medical therapy that alters disease progression in PSC, with the commonly prescribed ursodeoxycholic acid being shown to improve liver biochemistry at low-moderate doses (15-23 mg/kg/day) but not alter transplant-free survival or liver-related outcomes. Liver transplantation is the only option for patients who develop end-stage liver disease or refractory complications of PSC. Immunosuppressive and antifibrotic agents have not proven to be effective, but there is promise for manipulation of the gut microbiome with fecal microbiota transplantation and antibiotics. Bile acid manipulation via alternate synthetic bile acids such as norursodeoxycholic acid, or interaction at a transcriptional level via nuclear receptor agonists and fibrates have shown potential in phase II trials in PSC with several leading to larger phase III trials. In view of the enhanced malignancy risk, statins, and aspirin show potential for reducing the risk of colorectal cancer and cholangiocarcinoma in PSC patients. For patients who develop clinically relevant strictures with cholestatic symptoms and worsening liver function, balloon dilatation is safer compared with biliary stent insertion with equivalent clinical efficacy.}, }
@article {pmid37572993, year = {2023}, author = {Singh, A and Ashar, H and Butcher, JT and Ranjan, A}, title = {Age-associated changes in the gut microbiome impact efficacy of tumor immunomodulatory treatments.}, journal = {Experimental gerontology}, volume = {181}, number = {}, pages = {112268}, pmid = {37572993}, issn = {1873-6815}, support = {K01 AG064121/AG/NIA NIH HHS/United States ; R01 CA260974/CA/NCI NIH HHS/United States ; R37 CA239150/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Melanoma/therapy ; Fecal Microbiota Transplantation ; Aging ; Immunity ; }, abstract = {In-situ vaccination (ISV) utilizing nanoparticles (NPs) and therapeutic devices like focused ultrasound (FUS) can trigger immune-mediated killing of both treated and untreated cancer cells. However, the impact of confounding factors such as aging and gut microbiota composition on therapeutic outcomes remains poorly understood. In this study, we sequentially treated young mice (∼8 weeks) and old mice (>18 months) with bilateral melanoma using FUS and calreticulin nanoparticles (CRT-NP) to enhance immunogenic cell death. The combination of CRT-NP and FUS (CFUS) demonstrated greater efficacy in inducing regression of treated and untreated tumors in young mice compared to old mice. The diminished effectiveness in older mice was associated with significant differences in gut microbiome composition, characterized by alterations in bacterial species and splenic immune cells. Specifically, young mice exposed to CFUS exhibited higher abundance of Bacteroidetes and Verrucomicrobia, which was not observed in the aged cohorts. Turicibacter, Anaerotruncus, and Ruminiclostridium demonstrated negative correlations with CD8+ T cells but positive correlations with CD4+ T cells and MDSC cells in both age groups. Taxon set enrichment analysis revealed 58 significantly enriched host gene targets in the young cluster compared to only 11 in the aged cluster. These findings highlight the relationship between ISV treatment efficacy and gut microbiome composition, suggesting that interventions such as diet modification, probiotics, or fecal microbiota transplantation may hold potential as therapeutic strategies to enhance immune responses against solid tumors.}, }
@article {pmid37572864, year = {2023}, author = {Mansoor, AE and O'Neil, CA and Kwon, JH}, title = {The role of microbiome-based therapeutics for the reduction and prevention of antimicrobial-resistant organism colonization.}, journal = {Anaerobe}, volume = {83}, number = {}, pages = {102772}, doi = {10.1016/j.anaerobe.2023.102772}, pmid = {37572864}, issn = {1095-8274}, mesh = {Humans ; Feces ; *Microbiota ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Clostridium Infections/prevention &amp; control ; }, abstract = {The gut is host to a diverse array of microbiota that constitute a complex ecological system crucial to human physiology. Disruptors to the normal host microbiota, such as antimicrobials, can cause a loss of species diversity in the gut, reducing its ability to resist colonization by invading pathogens and potentially leading to colonization with antimicrobial resistant organisms (AROs). ARO negatively impact gut health by disrupting the usual heterogeneity of gut microbiota and have the potential to cause systemic disease. In recent years, fecal microbiota transplantation (FMT) has been increasingly explored in the management of specific disease states such as Clostridioides difficile infection (CDI). Promising data from management of CDI has led to considerable interest in understanding the role of therapeutics to restore the gut microbiota to a healthy state. This review aims to discuss key studies that highlight the current landscape, and explore existing clinical evidence, for the use of FMT and microbiome-based therapeutics in combating intestinal colonization with ARO. We also explore potential future directions of such therapeutics and discuss unaddressed needs in this field that merit further investigation.}, }
@article {pmid37571277, year = {2023}, author = {Wu, X and Li, P and Wang, W and Xu, J and Ai, R and Wen, Q and Cui, B and Zhang, F}, title = {The Underlying Changes in Serum Metabolic Profiles and Efficacy Prediction in Patients with Extensive Ulcerative Colitis Undergoing Fecal Microbiota Transplantation.}, journal = {Nutrients}, volume = {15}, number = {15}, pages = {}, pmid = {37571277}, issn = {2072-6643}, support = {82170563//National Natural Science Foundation of China/ ; 2021YFA0717004//National Key R&amp;D Program of China/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy/etiology ; Treatment Outcome ; Metabolome ; Metabolomics ; Feces ; }, abstract = {(1) Background: Fecal microbiota transplantation (FMT) is an effective treatment for ulcerative colitis (UC). Metabolomic techniques would assist physicians in clinical decision-making. (2) Methods: Patients with active UC undergoing FMT were enrolled in the study and monitored for 3 months. We explored short-term changes in the serum metabolic signatures of groups and the association between baseline serum metabolomic profiles and patient outcomes. (3) Results: Forty-four eligible patients were included in the analysis. Of them, 50.0% and 29.5% achieved clinical response and clinical remission, respectively, 3 months post-FMT. The top two significantly altered pathways in the response group were vitamin B6 metabolism and aminoacyl-tRNA biosynthesis. Both the remission and response groups exhibited an altered and enriched pathway for the biosynthesis of primary bile acid. We found a clear separation between the remission and non-remission groups at baseline, characterized by the higher levels of glycerophosphocholines, glycerophospholipids, and glycerophosphoethanolamines in the remission group. A random forest (RF) classifier was constructed with 20 metabolic markers selected by the Boruta method to predict clinical remission 3 months post-FMT, with an area under the curve of 0.963. (4) Conclusions: FMT effectively induced a response in patients with active UC, with metabolites partially improving post-FMT in the responsive group. A promising role of serum metabolites in the non-invasive prediction of FMT efficacy for UC demonstrated the value of metabolome-informed FMT in managing UC.}, }
@article {pmid37569381, year = {2023}, author = {Mingaila, J and Atzeni, A and Burokas, A}, title = {A Comparison of Methods of Gut Microbiota Transplantation for Preclinical Studies.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, pmid = {37569381}, issn = {1422-0067}, support = {No. 01.2.2-LMT-K-718-02-0014//European Regional Development Fund/ ; }, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome ; Feces/microbiology ; Reproducibility of Results ; RNA, Ribosomal, 16S/genetics ; Fecal Microbiota Transplantation/methods ; Anti-Bacterial Agents ; }, abstract = {The experimental details reported in preclinical fecal microbiota transplantation (FMT) protocols are highly inconsistent, variable, and/or incomplete. We therefore evaluated FMT from a human donor to antibiotic-induced microbial-depleted mice by exploring the effects of six techniques based on antibiotic (AB) or antibiotic + antimycotic (AB + T) gut decontamination, different administration routes, and different dosing intervals on the gut microbial population, assessed using 16S and 18S sequencing. In addition, we explored the effectiveness of FMT in terms of inflammation, physiological, and behavioral outcomes. Our results showed that intrarectal FMT at low dosing intervals better preserved the donor's gut bacterial community at genus level. Furthermore, we showed a lower abundance of several genera of fungi in animals treated with AB + T. In addition, we observed that AB + T gut decontamination followed by per os FMT, once every 3 days, affected behavioral parameters when compared to other FMT techniques. Accordingly, the same FMT groups that showed an association with some of the behavioral tests were also related to specific gut fungal genera, suggesting a possible mediation. Our findings may be useful for optimizing the practice of FMT and also in terms of donor microbiota preservation. This information may help to improve the reproducibility and reliability of FMT studies.}, }
@article {pmid37569349, year = {2023}, author = {Bendriss, G and MacDonald, R and McVeigh, C}, title = {Microbial Reprogramming in Obsessive-Compulsive Disorders: A Review of Gut-Brain Communication and Emerging Evidence.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, pmid = {37569349}, issn = {1422-0067}, mesh = {*Obsessive-Compulsive Disorder/microbiology/therapy ; Humans ; *Gastrointestinal Microbiome ; *Brain-Gut Axis/physiology ; *Dysbiosis/microbiology ; *Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; Brain/physiopathology ; }, abstract = {Obsessive-compulsive disorder (OCD) is a debilitating mental health disorder characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). Dysbiosis, an imbalance in the gut microbial composition, has been associated with various health conditions, including mental health disorders, autism, and inflammatory diseases. While the exact mechanisms underlying OCD remain unclear, this review presents a growing body of evidence suggesting a potential link between dysbiosis and the multifaceted etiology of OCD, interacting with genetic, neurobiological, immunological, and environmental factors. This review highlights the emerging evidence implicating the gut microbiota in the pathophysiology of OCD and its potential as a target for novel therapeutic approaches. We propose a model that positions dysbiosis as the central unifying element in the neurochemical, immunological, genetic, and environmental factors leading to OCD. The potential and challenges of microbial reprogramming strategies, such as probiotics and fecal transplants in OCD therapeutics, are discussed. This review raises awareness of the importance of adopting a holistic approach that considers the interplay between the gut and the brain to develop interventions that account for the multifaceted nature of OCD and contribute to the advancement of more personalized approaches.}, }
@article {pmid37569261, year = {2023}, author = {Cao, Z and Ling, X and Sun, P and Zheng, X and Zhang, H and Zhong, J and Yin, W and Fan, K and Sun, Y and Li, H and Sun, N}, title = {Matrine Targets Intestinal Lactobacillus acidophilus to Inhibit Porcine Circovirus Type 2 Infection in Mice.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, pmid = {37569261}, issn = {1422-0067}, support = {32172904//National Natural Science Foundation of China/ ; 2022YFD1801101//National Key Research and Development Program/ ; 202102140601019//Key Research and Development Plan of Shanxi Province/ ; 202204051001021//The special fund for Science and Technology Innovation Teams of Shanxi Province/ ; No. 20211331-16, No. 20211331-13//Shanxi "1331 Project"/ ; None//the earmarked fund for Modern Agro-industry Technology Research System/ ; }, mesh = {Mice ; Swine ; Animals ; *Circovirus ; Matrines ; Lactobacillus acidophilus ; *Swine Diseases ; RNA, Messenger/genetics ; }, abstract = {Porcine circovirus type 2 (PCV2) has caused huge economic losses to the pig industry across the world. Matrine is a natural compound that has been shown to regulate intestinal flora and has anti-PCV2 activity in mouse models. PCV2 infection can lead to changes in intestinal flora. The intestinal flora has proved to be one of the important pharmacological targets of the active components of Traditional Chinese Medicine. This study aimed to determine whether matrine exerts anti-PCV2 effects by regulating intestinal flora. In this study, fecal microbiota transplantation (FMT) was used to evaluate the effect of matrine on the intestinal flora of PCV2-infected Kunming (KM) mice. The expression of the Cap gene in the liver and the ileum, the relative expression of IL-1β mRNA, and the Lactobacillus acidophilus (L. acidophilus) gene in the ileum of mice were determined by real-time quantitative polymerase chain reaction (qPCR). ELISA was used to analyze the content of secretory immunoglobulin A (SIgA) in small intestinal fluid. L. acidophilus was isolated and identified from the feces of KM mice in order to study its anti-PCV2 effect in vivo. The expression of the Cap gene in the liver and the ileum and the relative expression of L. acidophilus and IL-1β mRNA in the ileum were determined by qPCR. The results showed that matrine could reduce the relative expression of IL-1β mRNA by regulating intestinal flora, and that its pharmacological anti-PCV2 and effect may be related to L. acidophilus. L. acidophilus was successfully isolated and identified from the feces of KM mice. The in vivo experiment revealed that administration of L. acidophilus also reduced the relative expression of IL-1β mRNA, and that it had anti-PCV2 effects in PCV2-infected mice. It was found that matrine could regulate the abundance of L. acidophilus in the gut of mice to exert an anti-PCV2 effect and inhibit PCV2-induced inflammatory response.}, }
@article {pmid37567034, year = {2023}, author = {Dai, Y and Shen, Z and Khachatryan, LG and Vadiyan, DE and Karampoor, S and Mirzaei, R}, title = {Unraveling mechanistic insights into the role of microbiome in neurogenic hypertension: A comprehensive review.}, journal = {Pathology, research and practice}, volume = {249}, number = {}, pages = {154740}, doi = {10.1016/j.prp.2023.154740}, pmid = {37567034}, issn = {1618-0631}, mesh = {Humans ; Dysbiosis/complications/metabolism/microbiology ; *Hypertension/drug therapy/metabolism ; *Microbiota ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Cardiovascular Diseases ; Inflammation/complications ; }, abstract = {Neurogenic hypertension, a complex and multifactorial cardiovascular disorder, is known to be influenced by various genetic, environmental, and lifestyle factors. In recent years, there has been growing interest in the role of the gut microbiome in hypertension pathogenesis. The bidirectional communication between the gut microbiota and the central nervous system, known as the microbiota-gut-brain axis, has emerged as a crucial mechanism through which the gut microbiota exerts its influence on neuroinflammation, immune responses, and blood pressure regulation. Recent studies have shown how the microbiome has a substantial impact on a variety of physiological functions, such as cardiovascular health. The increased sympathetic activity to the gut may cause microbial dysbiosis, increased permeability of the gut, and increased inflammatory reactions by altering a number of intestinal bacteria producing short-chain fatty acids (SCFAs) and the concentrations of lipopolysaccharide (LPS) in the plasma. Collectively, these microbial metabolic and structural compounds stimulate sympathetic stimulation, which may be an important stage in the onset of hypertension. The result is an upsurge in peripheral and central inflammatory response. In addition, it has recently been shown that a link between the immune system and the gut microbiota might play a significant role in hypertension. The therapeutic implications of the gut microbiome including probiotic usage, prebiotics, dietary modifications, and fecal microbiota transplantation in neurogenic hypertension have also been found. A large body of research suggests that probiotic supplementation might help reduce chronic inflammation and hypertension that have an association with dysbiosis in the gut microbiota. Overall, this review sheds light on the intricate interplay between the gut microbiome and neurogenic hypertension, providing valuable insights for both researchers and clinicians. As our knowledge of the microbiome's role in hypertension expands, novel therapeutic strategies and diagnostic biomarkers may pave the way for more effective management and prevention of this prevalent cardiovascular disorder. Exploring the potential of the microbiome in hypertension offers an exciting avenue for future research and offers opportunities for precision medicine and improved patient care.}, }
@article {pmid37566894, year = {2023}, author = {Allegretti, JR and Khanna, S and Feuerstadt, P}, title = {Practical Use of Fecal Microbiota Spores, Live BRPK for the Prevention of Recurrent Clostridioides difficile Infection.}, journal = {The American journal of gastroenterology}, volume = {118}, number = {12}, pages = {2106-2108}, doi = {10.14309/ajg.0000000000002463}, pmid = {37566894}, issn = {1572-0241}, mesh = {Humans ; Spores, Bacterial ; *Clostridium Infections/prevention &amp; control ; Feces ; *Microbiota ; Fecal Microbiota Transplantation ; Recurrence ; Treatment Outcome ; }, }
@article {pmid37566569, year = {2023}, author = {Hong, Y and Dong, H and Zhou, J and Luo, Y and Yuan, MM and Zhan, JF and Liu, YL and Xia, JY and Zhang, L}, title = {Aged gut microbiota contribute to different changes in antioxidant defense in the heart and liver after transfer to germ-free mice.}, journal = {PloS one}, volume = {18}, number = {8}, pages = {e0289892}, pmid = {37566569}, issn = {1932-6203}, mesh = {Mice ; Animals ; *Antioxidants ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Liver ; Fecal Microbiota Transplantation ; Glutathione ; Superoxide Dismutase ; }, abstract = {Age-associated impairment in antioxidant defense is an important cause of oxidative stress, and elderly individuals are usually associated with gut microbiota (GM) changes. Studies have suggested a potential relationship between the GM and changes in antioxidant defense in aging animals. Direct evidence regarding the impact of aging-associated shifts in GM on the antioxidant defense is lacking. The heart is a kind of postmitotic tissue, which is more prone to oxidative stress than the liver (mitotic tissue). To test and compare the influence of an aged GM on antioxidant defense changes in the heart and liver of the host, in this study, GM from young adolescent (5 weeks) or aged (20 months) mice was transferred to young adolescent (5 weeks) germ-free (GF) mice (N = 5 per group) by fecal microbiota transplantation (FMT). Four weeks after the first FMT was performed, fecal samples were collected for 16S rRNA sequencing. Blood, heart and liver samples were harvested for oxidative stress marker and antioxidant defense analysis. The results showed that mice that received young or aged microbiota showed clear differences in GM composition and diversity. Mice that received aged microbiota had a lower ratio of Bacteroidetes/Firmicutes in GM at the phylum level and an increased relative abundance of four GM genera: Akkermansia, Dubosiella, Alistipes and Rikenellaceae_RC9_gut_group. In addition, GM α-diversity scores based on the Shannon index and Simpson index were significantly higher in aged GM-treated mice. Oxidative stress marker and antioxidant defense tests showed that FMT from aged donors did not have a significant influence on malondialdehyde content in serum, heart and liver. However, the capacity of anti-hydroxyl radicals in the heart and liver, as well as the capacity of anti-superoxide anions in the liver, were significantly increased in mice with aged microbiota. FMT from aged donors increased the activities of Cu/Zn superoxide SOD (Cu/Zn-SOD), catalase (CAT) and glutathione-S-transferase in the heart, as well as the activity of Cu/Zn-SOD in the liver. Positive correlations were found between Cu/Zn-SOD activity and radical scavenging capacities. On the other hand, glutathione reductase activity and glutathione content in the liver were decreased in mice that received aged GM. These findings suggest that aged GM transplantation from hosts is sufficient to influence the antioxidant defense system of young adolescent recipients in an organ-dependent manner, which highlights the importance of the GM in the aging process of the host.}, }
@article {pmid37562707, year = {2023}, author = {Zhang, Z and Li, Q and Zhang, S and Liu, Y and Lu, G and Wen, Q and Cui, B and Zhang, F and Zhang, F}, title = {Washed microbiota transplantation targeting both gastrointestinal and extraintestinal symptoms in patients with irritable bowel syndrome.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {127}, number = {}, pages = {110839}, doi = {10.1016/j.pnpbp.2023.110839}, pmid = {37562707}, issn = {1878-4216}, mesh = {Humans ; *Irritable Bowel Syndrome/psychology ; *Gastrointestinal Microbiome ; Quality of Life ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Diseases ; *Sleep Wake Disorders ; }, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) has been reported with the treatment potential for irritable bowel syndrome (IBS). However, the knowledge of its effect on extraintestinal symptoms of IBS is limited. This study aimed to evaluate the efficacy of the improved methodology of FMT, washed microbiota transplantation (WMT), on sleep disturbances, and psychological and gastrointestinal symptoms among patients with IBS.<br><br>METHODS: This was a prospective observational study involving patients with IBS who underwent WMT. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The Gastrointestinal Symptom Rating Scale (GSRS) and IBS Severity Scoring System (IBS-SSS) were used to evaluate gastrointestinal symptoms and IBS severity, respectively. The Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) were used to evaluate depression and anxiety, respectively. All the symptoms were evaluated at baseline and one month after WMT. A multiple logistic regression model was used to determine the predictive factors of sleep improvement one month after WMT.<br><br>RESULTS: Seventy-three patients with IBS were included in the study. Sleep quality (Z&#xa0;=&#xa0;-4.211, P&#xa0;<&#xa0;0.001), anxiety (Z&#xa0;=&#xa0;-4.775, P&#xa0;<&#xa0;0.001), depression (Z&#xa0;=&#xa0;-4.610, P&#xa0;<&#xa0;0.001), gastrointestinal symptoms (Z&#xa0;=&#xa0;-5.364, P&#xa0;<&#xa0;0.001), and IBS severity (Z&#xa0;=&#xa0;-6.468, P&#xa0;<&#xa0;0.001) significantly improved one month after WMT in all patients. The scores of the five components of PSQI including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, and sleep disturbances decreased in 52 patients with poor sleep quality (all P&#xa0;<&#xa0;0.05). Baseline sleep duration scores were identified as an independent predictive factor of sleep improvement one month after WMT in patients with poor sleep quality (OR 2.180 [95% CI&#xa0;=&#xa0;1.017-4.673]; P&#xa0;=&#xa0;0.045). Patients that experienced sleep improvement demonstrated greater alleviation in depression (Z&#xa0;=&#xa0;-1.990, P&#xa0;=&#xa0;0.047) and IBS severity (Z&#xa0;=&#xa0;-2.486, P&#xa0;=&#xa0;0.013) compared with patients without sleep improvement.<br><br>CONCLUSION: This study suggested that WMT might be a promising therapy for patients with IBS, especially those with comorbid sleep and psychological disorders.}, }
@article {pmid37560802, year = {2023}, author = {Shirley, DA and Tornel, W and Warren, CA and Moonah, S}, title = {Clostridioides difficile Infection in Children: Recent Updates on Epidemiology, Diagnosis, Therapy.}, journal = {Pediatrics}, volume = {152}, number = {3}, pages = {}, pmid = {37560802}, issn = {1098-4275}, support = {R01 DK131313/DK/NIDDK NIH HHS/United States ; R34 AI165304/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Child ; Humans ; Child, Preschool ; Anti-Bacterial Agents/adverse effects ; *Clostridioides difficile ; Vancomycin/adverse effects ; *Clostridium Infections/diagnosis/drug therapy/epidemiology ; Diarrhea/drug therapy ; }, abstract = {Clostridioides (formerly Clostridium) difficile is the most important infectious cause of antibiotic-associated diarrhea worldwide and a leading cause of healthcare-associated infection in the United States. The incidence of C. difficile infection (CDI) in children has increased, with 20 000 cases now reported annually, also posing indirect educational and economic consequences. In contrast to infection in adults, CDI in children is more commonly community-associated, accounting for three-quarters of all cases. A wide spectrum of disease severity ranging from asymptomatic carriage to severe diarrhea can occur, varying by age. Fulminant disease, although rare in children, is associated with high morbidity and even fatality. Diagnosis of CDI can be challenging as currently available tests detect either the presence of organism or disease-causing toxin but cannot distinguish colonization from infection. Since colonization can be high in specific pediatric groups, such as infants and young children, biomarkers to aid in accurate diagnosis are urgently needed. Similar to disease in adults, recurrence of CDI in children is common, affecting 20% to 30% of incident cases. Metronidazole has long been considered the mainstay therapy for CDI in children. However, new evidence supports the safety and efficacy of oral vancomycin and fidaxomicin as additional treatment options, whereas fecal microbiota transplantation is gaining popularity for recurrent infection. Recent advancements in our understanding of emerging epidemiologic trends and management of CDI unique to children are highlighted in this review. Despite encouraging therapeutic advancements, there remains a pressing need to optimize CDI therapy in children, particularly as it pertains to severe and recurrent disease.}, }
@article {pmid37558058, year = {2023}, author = {Arditi, Z and Bunyavanich, S}, title = {Commensal collaborations: Food allergy and the microbiome.}, journal = {The Journal of allergy and clinical immunology}, volume = {152}, number = {6}, pages = {1417-1419}, pmid = {37558058}, issn = {1097-6825}, support = {R01 AI147028/AI/NIAID NIH HHS/United States ; U19 AI136053/AI/NIAID NIH HHS/United States ; UM1 AI173380/AI/NIAID NIH HHS/United States ; }, }
@article {pmid37558018, year = {2023}, author = {Zhou, Y and Jia, Y and Xu, N and Tang, L and Chang, Y}, title = {Auricularia auricula-judae (Bull.) polysaccharides improve obesity in mice by regulating gut microbiota and TLR4/JNK signaling pathway.}, journal = {International journal of biological macromolecules}, volume = {250}, number = {}, pages = {126172}, doi = {10.1016/j.ijbiomac.2023.126172}, pmid = {37558018}, issn = {1879-0003}, mesh = {Auricularia ; MAP Kinase Signaling System ; Obesity/metabolism ; Polysaccharides/pharmacology ; *Gastrointestinal Microbiome ; Humans ; *Toll-Like Receptor 4/metabolism ; Mice ; Animals ; }, abstract = {Obesity has emerged as a crucial factor impacting people's lives, and gut microbiota disorders contribute to its development and progression. Auricularia auricula-judae (Bull.) polysaccharides (AAPs), a traditional functional food in Asia, exhibit potential anti-obesity effects. However, the specific mechanism still needs to be further confirmed. This study investigated the beneficial effects and specific mechanisms of AAPs on obesity. Firstly, AAPs showed significant improvements in overweight, insulin resistance, glucose and lipid metabolism disorders, and liver damage in obese mice. Additionally, AAPs ameliorated gut microbiota disorders, promoting the proliferation of beneficial bacteria like Lactobacillus and Roseburia, resulting in increased levels of SCFAs, folate, and cobalamin. Simultaneously, AAPs inhibited the growth of harmful bacteria, thereby protecting intestinal barrier function, improving endotoxemia, and decreasing the levels of inflammatory factors such as TNF-α and IL-6. Furthermore, AAPs can inhibit the TLR4/JNK signaling pathway while promoting the activation of AKT and AMPK. Importantly, our study underscored the pivotal role of gut microbiota in the anti-obesity effects of AAPs, as evidenced by fecal microbiota transplantation experiments. In conclusion, our findings elucidated that AAPs improve obesity by regulating gut microbiota and TLR4/JNK signaling pathway, offering novel perspectives for further conclusion the anti-obesity potential of AAPs.}, }
@article {pmid37557963, year = {2023}, author = {Guzzardi, MA and La Rosa, F and Granziera, F and Panetta, D and Pardo-Tendero, M and Barone, M and Turroni, S and Faita, F and Kusmic, C and Brigidi, P and Monleon, D and Iozzo, P}, title = {Gut-derived metabolites mediating cognitive development in 5-year-old children: Early-life transplant in mice has lasting effects throughout adulthood.}, journal = {Brain, behavior, and immunity}, volume = {114}, number = {}, pages = {94-110}, doi = {10.1016/j.bbi.2023.08.009}, pmid = {37557963}, issn = {1090-2139}, abstract = {The gut microbiota has been causally linked to cognitive development. We aimed to identify metabolites mediating its effect on cognitive development, and foods or nutrients related to most promising metabolites. Faeces from 5-year-old children (DORIAN-PISAC cohort, including 90 general population families with infants, 42/48 females/males, born in 2011-2014) were transplanted (FMT) into C57BL/6 germ-free mice. Children and recipient mice were stratified by cognitive phenotype, or based on protective metabolites. Food frequency questionnaires were obtained in children. Cognitive measurements in mice included five Y-maze tests until 23 weeks post-FMT, and (at 23 weeks) PET-CT for brain metabolism and radiodensity, and ultrasound-based carotid vascular indices. Children (faeces, urine) and mice (faeces, plasma) metabolome was measured by 1H NMR spectroscopy, and the faecal microbiota was profiled in mice by 16S rRNA amplicon sequencing. Cognitive scores of children and recipient mice were correlated. FMT-dependent modifications of brain metabolism were observed. Mice receiving FMT from high-cognitive or protective metabolite-enriched children developed superior cognitive-behavioural performance. A panel of metabolites, namely xanthine, hypoxanthine, formate, mannose, tyrosine, phenylalanine, glutamine, was found to mediate the gut-cognitive axis in donor children and recipient mice. Vascular indices partially explained the metabolite-to-phenotype relationships. Children's consumption of legumes, whole-milk yogurt and eggs, and intake of iron, zinc and vitamin D appeared to support protective gut metabolites. Overall, metabolites involved in inflammation, purine metabolism and neurotransmitter synthesis mediate the gut-cognitive axis, and holds promise for screening. The related dietary and nutritional findings offer leads to microbiota-targeted interventions for cognitive protection, with long-lasting effects.}, }
@article {pmid37555952, year = {2023}, author = {Benešová, I and Křížová, &#x13d; and Kverka, M}, title = {Microbiota as the unifying factor behind the hallmarks of cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {15}, pages = {14429-14450}, pmid = {37555952}, issn = {1432-1335}, support = {NV19-03-00179//Agentura Pro Zdravotnick&#xfd; V&#xfd;zkum &#x10c;esk&#xe9; Republiky/ ; LQ200202105//Mikrobiologick&#xfd; &#xda;stav, Akademie V&#x11b;d &#x10c;esk&#xe9; Republiky/ ; }, abstract = {The human microbiota is a complex ecosystem that colonizes body surfaces and interacts with host organ systems, especially the immune system. Since the composition of this ecosystem depends on a variety of internal and external factors, each individual harbors a unique set of microbes. These differences in microbiota composition make individuals either more or less susceptible to various diseases, including cancer. Specific microbes are associated with cancer etiology and pathogenesis and several mechanisms of how they drive the typical hallmarks of cancer were recently identified. Although most microbes reside in the distal gut, they can influence cancer initiation and progression in distant tissues, as well as modulate the outcomes of established cancer therapies. Here, we describe the mechanisms by which microbes influence carcinogenesis and discuss their current and potential future applications in cancer diagnostics and management.}, }
@article {pmid37554826, year = {2023}, author = {Chen, Y and Chai, H and Li, Z and Liu, B and Tan, M and Li, S and Ma, Y}, title = {Gut microbiota and their metabolite profiles following peripheral nerve xenotransplantation.}, journal = {Heliyon}, volume = {9}, number = {8}, pages = {e18529}, pmid = {37554826}, issn = {2405-8440}, abstract = {BACKGROUND: Intestinal pathogens are associated with xenotransplantation tolerance and rejection. However, changes in the gut microbiota in patients who have undergone peripheral nerve xenotransplantation and their association with immune rejection have not yet been reported.<br><br>OBJECTIVE: We aimed to explore intestinal microbes and their metabolites at different time points after peripheral nerve transplantation to provide new insight into improving transplant tolerance.<br><br>METHODS: A peripheral nerve xenotransplantation model was constructed by suturing the segmented nerves of Sprague Dawley rats to those of C57 male mice using xenotransplantation nerve bridging. Fecal samples and intestinal contents were collected at three time points: before surgery (Pre group; n&#xa0;=&#xa0;10), 1 month after transplantation (Pos1 m group; n&#xa0;=&#xa0;10), and 3 months after transplantation (Pos3 m group; n&#xa0;=&#xa0;10) for 16S DNA sequencing and nontargeted metabolome detection.<br><br>RESULTS: Alpha diversity results suggested that species diversity was significantly downregulated after peripheral nerve xenotransplantation. There were six gut flora genera with significantly different expression levels after xenotransplantation: four were downregulated and two were upregulated. A comparison of the Pre vs. Pos1 m groups and the Pos1 m vs. Pos3 m groups revealed that the most significant differentially expressed Kyoto Encyclopedia of Genes and Genomes metabolite pathways were involved in phenylalanine, tyrosine, and tryptophan biosynthesis, as well as histidine metabolism. Metabolites with a strong relationship to the differentially expressed microbial flora were identified.<br><br>CONCLUSION: Our study found lower gut microbiome diversity, with increased short-chain fatty acid (SCFA)-producing and sulfate-reducing bacteria at 1 month post peripheral nerve xenotransplantation, and these were decreased at 3 months post-transplantation. The identification of specific bacterial metabolites is essential for recognizing potential diagnostic markers of xenotransplantation rejection or characterizing therapeutic targets to prevent post-transplant infection.}, }
@article {pmid37554593, year = {2023}, author = {Sadagopan, A and Mahmoud, A and Begg, M and Tarhuni, M and Fotso, M and Gonzalez, NA and Sanivarapu, RR and Osman, U and Latha Kumar, A and Mohammed, L}, title = {Understanding the Role of the Gut Microbiome in Diabetes and Therapeutics Targeting Leaky Gut: A Systematic Review.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e41559}, pmid = {37554593}, issn = {2168-8184}, abstract = {The gut microbiota has been studied and continues to be a developing area in the pathognomic development of metabolic diseases like diabetes. Treatment with diet changes, the addition of supplements like prebiotics/probiotics, and the impact of fecal microbial transplantation can be correlated to targeting changes in dysbiosis. Understanding the impacts of various anti-hyperglycemic agents such as metformin and the implications of post-bariatric surgery on the gut microbiota diversity has emerged. These areas of study are crucial to understanding the pathognomic aspects of diabetes disease progression at the microbial level of metabolic and inflammatory mechanisms, which may give more insight into focusing on the role of diet prebiotic/probiotic supplements as potential forms of prospective management in diabetes and the development of more agents that target gut microbiota, which harbors low-grade inflammation. Intestinal dysbiosis was consistently observed in the mechanism of gut microbial change in diabetic individuals, contributing to reduced insulin sensitivity and poor glycemic control. This systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 checklist. We performed a literature search using the PubMed, Google Scholar and Science Direct databases in accordance with the eligibility criteria and ultimately selected 14 articles for final analysis. The Scale for the Assessment of Narrative Review Articles (SANRA) and the PRISMA 2020 checklist were used to assess the quality of selected articles for cross-sectional studies, traditional literature reviews, and systematic reviews, respectively. We collected papers from 2012 to 2022 for this review. We gathered articles from databases, such as this study, which show there is a strong connection between microbiota and diabetes that appears to exist. The objective is to assess and identify any dietary and therapeutic agents that may alter the microbiota and potentially target and modulate insulin sensitivity. This review article will discuss the pathophysiological effects of gut microbiota in diabetes management and the impact of various gut biodiversity therapeutics that can aid in reversing insulin sensitivity.}, }
@article {pmid37554355, year = {2023}, author = {Kwak, MJ and Kim, SH and Kim, HH and Tanpure, R and Kim, JI and Jeon, BH and Park, HK}, title = {Psychobiotics and fecal microbial transplantation for autism and attention-deficit/hyperactivity disorder: microbiome modulation and therapeutic mechanisms.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1238005}, pmid = {37554355}, issn = {2235-2988}, mesh = {Humans ; *Autistic Disorder ; *Attention Deficit Disorder with Hyperactivity/therapy ; *Autism Spectrum Disorder/therapy ; *Microbiota ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, abstract = {Dysbiosis of the gut microbiome is thought to be the developmental origins of the host's health and disease through the microbiota-gut-brain (MGB) axis: such as immune-mediated, metabolic, neurodegenerative, and neurodevelopmental diseases. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common neurodevelopmental disorders, and growing evidence indicates the contribution of the gut microbiome changes and imbalances to these conditions, pointing to the importance of considering the MGB axis in their treatment. This review summarizes the general knowledge of gut microbial colonization and development in early life and its role in the pathogenesis of ASD/ADHD, highlighting a promising therapeutic approach for ASD/ADHD through modulation of the gut microbiome using psychobiotics (probiotics that positively affect neurological function and can be applied for the treatment of psychiatric diseases) and fecal microbial transplantation (FMT).}, }
@article {pmid37554279, year = {2023}, author = {Chen, PP and Zhang, JX and Li, XQ and Li, L and Wu, QY and Liu, L and Wang, GH and Ruan, XZ and Ma, KL}, title = {Outer membrane vesicles derived from gut microbiota mediate tubulointerstitial inflammation: a potential new mechanism for diabetic kidney disease.}, journal = {Theranostics}, volume = {13}, number = {12}, pages = {3988-4003}, pmid = {37554279}, issn = {1838-7640}, mesh = {Rats ; Mice ; Animals ; *Diabetic Nephropathies/pathology ; *Diabetes Mellitus, Experimental ; *Gastrointestinal Microbiome ; Inflammation ; Caspases ; }, abstract = {Rationale: Chronic tubulointerstitial inflammation is a common pathological process in diabetic kidney disease (DKD). However, its underlying mechanism is largely unknown. This study aims at investigating the role of gut microbiota-derived outer membrane vesicles (OMVs) in tubulointerstitial inflammation in DKD. Methods: Gut microbiota in diabetes mellitus rats was manipulated by microbiota depletion and fecal microbiota transplantation to explore its role in tubulointerstitial inflammation. To check the direct effects of OMVs, fecal bacterial extracellular vesicles (fBEVs) were administrated to mice orally and HK-2 cells in vitro. For mechanistic investigations, HK-2 cells were treated with small interfering RNA against caspase-4 and fBEVs pre-neutralized by polymyxin B. Results: By performing gut microbiota manipulation, it was confirmed that gut microbiota mediated tubulointerstitial inflammation in DKD. In diabetic rats, gut microbiota-derived OMVs were increased and were clearly detected in distant renal tubulointerstitium. Diabetic fBEVs directly administered by gavage translocated into tubular epithelial cells and induced tubulointerstitial inflammation and kidney injury. In vitro, OMVs were internalized through various endocytic pathways and triggered cellular inflammatory response. Mechanistically, it was revealed that OMVs-derived lipopolysaccharide induced tubular inflammation, which was mediated by the activation of the caspase-11 pathway. Conclusions: Increased OMVs due to dysbiosis translocated through leaky gut barrier into distant tubulointerstitium and induced cellular inflammation and renal tubulointerstitial injury in DKD. These findings enrich the mechanism understanding of how gut microbiota and its releasing OMVs influence the development and progression of kidney disease.}, }
@article {pmid37553783, year = {2023}, author = {El Jurdi, N and Holtan, SG and Hoeschen, A and Velguth, J and Hillmann, B and Betts, BC and MacMillan, ML and Weisdorf, DJ and Khoruts, A and Rashidi, A and Shields-Cutler, R}, title = {Pre-transplant and longitudinal changes in faecal microbiome characteristics are associated with subsequent development of chronic graft-versus-host disease.}, journal = {British journal of haematology}, volume = {203}, number = {2}, pages = {288-294}, doi = {10.1111/bjh.19016}, pmid = {37553783}, issn = {1365-2141}, support = {//UMN Grant-in-Aid/ ; //Chainbreaker/ ; //BRAINS/ ; }, abstract = {The role of the gastrointestinal microbiome in predisposing to chronic graft-versus-host disease (cGVHD), an immune-mediated haematopoietic cell transplant (HCT) complication, is not well defined. We examined the relationship of the host faecal microbiome with subsequent cGVHD development by analysing baseline stool samples as well as post-HCT changes in microbiome composition and metabolite pathway analyses. We analysed pre-transplant baseline samples from 11 patients who subsequently developed cGVHD compared to 13 controls who did not develop acute GVHD or cGVHD at any time. We found a significant differential abundance of multiple taxa at baseline between cGVHD versus controls, including the Actinobacteria phylum and Clostridium genus. A subgroup analysis of longitudinal samples within each patient revealed a greater loss of alpha diversity from baseline to post-engraftment in patients who subsequently developed cGVHD. Metabolic pathways analysis revealed that two pathways associated with short-chain fatty acid metabolism were enriched in cGVHD patient microbiomes: β-oxidation and acyl-CoA synthesis, and γ-aminobutyrate shunt. In contrast, a tryptophan catabolism pathway was enriched in controls. Our findings show a distinct pattern of baseline microbiome and metabolic capacity that may play a role in modulating alloreactivity in patients developing cGVHD. These findings support the therapeutic potential of microbiome manipulation for cGVHD prevention.}, }
@article {pmid37550190, year = {2023}, author = {Zheng, YY and Yang, XT and Lin, GQ and Bian, MR and Si, YJ and Zhang, XX and Zhang, YM and Wu, DP}, title = {[Clinical study of 19 cases of steroid-refractory gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with fecal microbiota transplantation].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {44}, number = {5}, pages = {401-407}, pmid = {37550190}, issn = {0253-2727}, support = {M2020058//General Project of Medical Scientific Research of Jiangsu Provincial Health Commission/ ; SBK202003003//Opening Project of Sample Bank of Biological Resources of Key Diseases in Jiangsu Province/ ; XZSYSKF2020038, XZSYSKF2021026//Opening Project of Jiangsu Key Laboratory/ ; }, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; Treatment Outcome ; *Graft vs Host Disease/therapy/diagnosis/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Steroids ; }, abstract = {Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.}, }
@article {pmid37549868, year = {2023}, author = {Zong, X and Zhang, H and Zhu, L and Deehan, EC and Fu, J and Wang, Y and Jin, M}, title = {Auricularia auricula polysaccharides attenuate obesity in mice through gut commensal Papillibacter cinnamivorans.}, journal = {Journal of advanced research}, volume = {52}, number = {}, pages = {203-218}, pmid = {37549868}, issn = {2090-1224}, mesh = {Auricularia ; RNA, Ribosomal, 16S ; Polysaccharides/pharmacology ; *Proteomics ; Clostridiales ; Mice ; Animals ; Lipids ; *Obesity/drug therapy/microbiology ; }, abstract = {INTRODUCTION: Auricularia auricula is a well-known traditional edible and medical fungus with high nutritional and pharmacological values, as well as metabolic and immunoregulatory properties. Nondigestible fermentable polysaccharides are identified as primary bioactive constituents of Auricularia auricula extracts. However, the exact mechanisms underlying the effects of Auricularia auricula polysaccharides (AAP) on obesity and related metabolic endpoints, including the role of the gut microbiota, remain insufficiently understood.<br><br>METHODS: The effects of AAP on obesity were assessed within high-fat diet (HFD)-based mice through obesity trait analysis and metabolomic profiling. To determine the mechanistic role of the gut microbiota in observed anti-obesogenic effects AAP, faecal microbiota transplantation (FMT) and pseudo-germ-free mice model treated with antibiotics were also applied, together with 16S rRNA genomic-derived taxonomic profiling.<br><br>RESULTS: High-fat diet (HFD) murine exposure to AAP thwarted weight gains, reduced fat depositing and enhanced glucose tolerance, together with upregulating thermogenesis proteomic biomarkers within adipose tissue. Serum metabolome indicated these effects were associated with changes in fatty acid metabolism. Intestine-dwelling microbial population assessments discovered that AAP selectively enhanced Papillibacter cinnamivorans, a commensal bacterium with reduced presence in HFD mice. Notably, HFD mice treated with oral formulations of P. cinnamivorans attenuated obesity, which was linked to decreased intestinal lipid transportation and hepatic thermogenesis. Mechanistically, it was demonstrated that P. cinnamivorans regulated intestinal lipids metabolism and liver thermogenesis by reducing the proinflammatory response and gut permeability in a JAK-STAT signaling-related manner.<br><br>CONCLUSION: Datasets from the present study show that AAP thwarted dietary-driven obesity and metabolism-based disorders by regulating intestinal lipid transportation, a mechanism that is dependent on the gut commensal P. cinnamivorans. These results indicated AAP and P. cinnamivorans as newly identified pre- and probiotics that could serve as novel therapeutics against obesity.}, }
@article {pmid37549451, year = {2023}, author = {Chen, H and Wang, C and Bai, J and Song, J and Bu, L and Liang, M and Suo, H}, title = {Targeting microbiota to alleviate the harm caused by sleep deprivation.}, journal = {Microbiological research}, volume = {275}, number = {}, pages = {127467}, doi = {10.1016/j.micres.2023.127467}, pmid = {37549451}, issn = {1618-0623}, mesh = {Humans ; Sleep Deprivation ; *Microbiota ; *Probiotics/therapeutic use ; Prebiotics ; *Gastrointestinal Microbiome ; }, abstract = {Sleep deprivation has become a common health hazard, affecting 37-58% of the population and promoting the occurrence and development of many diseases. To date, effective treatment strategies are still elusive. Accumulating evidence indicates that modulating the intestinal microbiota harbors significant potential for alleviating the deleterious impacts of sleep deprivation. This paper first reviews the effects of sleep deprivation on gastrointestinal diseases, metabolic diseases, and neuropsychiatric diseases, discussing its specific mechanisms of influence. We then focus on summarizing existing interventions, including probiotics, melatonin, prebiotics, diet, and fecal microbiota transplantation (FMT). Finally, we have discussed the advantages and limitations of each strategy. Compared with other strategies, probiotics showed a high potential in alleviating sleep deprivation-related hazards due to their reduced risk and high security. We suggest that future research should focus on the specific mechanisms by which probiotics mitigate the harms of sleep deprivation, such insights may unveil novel pathways for treating diseases exacerbated by insufficient sleep.}, }
@article {pmid37549387, year = {2023}, author = {Kanjee, Z and Allegretti, JR and Alonso, CD and Burns, RB}, title = {How Would You Manage This Patient With Clostridioides difficile Infection? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.}, journal = {Annals of internal medicine}, volume = {176}, number = {8}, pages = {1101-1108}, doi = {10.7326/M23-0754}, pmid = {37549387}, issn = {1539-3704}, mesh = {Female ; Humans ; Middle Aged ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Teaching Rounds ; *Clostridioides difficile ; Practice Guidelines as Topic ; }, abstract = {The Infectious Diseases Society of America/Society for Healthcare Epidemiology of America and the American College of Gastroenterology recently released updated guidelines on management of patients with Clostridioides difficile infection. Although these 2 guidelines generally agree, there are a few important differences in their advice to clinicians. In these rounds, 2 experts, an infectious diseases specialist and a gastroenterologist, discuss antibiotic treatment options for nonsevere disease, the role of fecal microbiota transplantation for fulminant disease, and the use of bezlotoxumab to prevent recurrence in the context of Ms. C, a 48-year-old woman with fulminant C difficile infection.}, }
@article {pmid37548864, year = {2023}, author = {Philips, CA and Ahamed, R and Abduljaleel, JK and Rajesh, S and Tharakan, A and Augustine, P}, title = {Significant gut microbiota related to patterns of drinking and alcohol relapse in patients with alcoholic hepatitis undergoing stool transplant or corticosteroid therapy.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {42}, number = {5}, pages = {724-730}, pmid = {37548864}, issn = {0975-0711}, mesh = {Animals ; Humans ; *Hepatitis, Alcoholic/therapy ; Fecal Microbiota Transplantation ; Retrospective Studies ; *Gastrointestinal Microbiome ; Ethanol ; Feces/microbiology ; Adrenal Cortex Hormones ; Recurrence ; Treatment Outcome ; }, abstract = {Alcohol-induced gut microbiota (GM) alterations are linked to alcohol use disorder (AUD) pathogenesis. Healthy donor stool transplant (fecal microbiota transplant [FMT]) reduced alcohol desire and improved clinical outcomes in small animal and human studies. Baseline and post-therapy-related GM changes in a real-world cohort with severe alcohol-related liver disease and AUD, patterns of drinking, and relapse have not been studied. We prospectively analyzed retrospective clinical data and stored samples to examine GM alterations in a cohort of severe alcohol-associated hepatitis (SAH) patients who underwent FMT or corticosteroid treatment followed for at least 12 months. The GM changes at baseline in the context of a pattern of drinking (binge vs. every day) and baseline and post-treatment alcohol relapse status (relapser vs. non-relapser). We identified 28 patients on FMT and 25 on corticosteroids who survived 1 year post-treatment. After necessary exclusions, the final cohort for various grouped GM analysis included 16 patients in the FMT arm and 14 on corticosteroids. Pedobacter and Streptophyta species at the commencement of treatment predicted alcohol relapse in steroid-ineligible patients receiving FMT and steroid-treated patients, respectively. At 6-12 months post-FMT, non-relapsers had elevated short-chain fatty acid-producing bacterial taxa linked with lower alcohol cravings. Alcohol relapse was significantly more in those on steroid therapy and was associated with the upregulation of the nucleotide metabolism pathway related to ethanol metabolism. We demonstrate pertinent baseline and post-treatment intestinal bacterial alterations that impact patterns of AUD patterns and relapse in SAH patients in the context of the therapy offered.}, }
@article {pmid37548627, year = {2023}, author = {Ramos Maia, DR and Otsuki, DA and Rodrigues, CE and Zboril, S and Sanches, TR and Neto, AND and Andrade, L and Auler, JOC}, title = {TREATMENT WITH HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS IN A PIG MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY: EFFECTS ON MICROVASCULAR ENDOTHELIAL CELLS AND TUBULAR CELLS IN THE KIDNEY.}, journal = {Shock (Augusta, Ga.)}, volume = {60}, number = {3}, pages = {469-477}, doi = {10.1097/SHK.0000000000002191}, pmid = {37548627}, issn = {1540-0514}, mesh = {Humans ; *Acute Kidney Injury/therapy/chemically induced ; Endothelial Cells/metabolism ; Kidney/metabolism ; *Mesenchymal Stem Cell Transplantation ; *Mesenchymal Stem Cells/metabolism ; NF-kappa B/metabolism ; *Sepsis/complications/therapy/metabolism ; Toll-Like Receptor 4/metabolism ; Umbilical Cord/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Animals ; Swine ; }, abstract = {Background: Approximately 50% of patients with sepsis develop acute kidney injury (AKI), which is predictive of poor outcomes, with mortality rates of up to 70%. The endothelium is a major target for treatments aimed at preventing the complications of sepsis. We hypothesized that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could attenuate tubular and endothelial injury in a porcine model of sepsis-induced AKI. Methods: Anesthetized pigs were induced to fecal peritonitis, resulting in septic shock, and were randomized to treatment with fluids, vasopressors, and antibiotics (sepsis group; n = 11) or to that same treatment plus infusion of 1 × 10 6 cells/kg of hUC-MSCs (sepsis+MSC group; n = 11). Results: At 24 h after sepsis induction, changes in serum creatinine and mean arterial pressure were comparable between the two groups, as was mortality. However, the sepsis+MSC group showed some significant differences in comparison with the sepsis group: lower fractional excretions of sodium and potassium; greater epithelial sodium channel protein expression; and lower protein expression of the Na-K-2Cl cotransporter and aquaporin 2 in the renal medulla. Expression of P-selectin, thrombomodulin, and vascular endothelial growth factor was significantly lower in the sepsis+MSC group than in the sepsis group, whereas that of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) was lower in the former. Conclusion: Treatment with hUC-MSCs seems to protect endothelial and tubular cells in sepsis-induced AKI, possibly via the TLR4/NF-κB signaling pathway. Therefore, it might be an effective treatment for sepsis-induced AKI.}, }
@article {pmid37546903, year = {2023}, author = {Shrode, RL and Ollberding, NJ and Mangalam, AK}, title = {Looking at the Full Picture: Utilizing Topic Modeling to Determine Disease-Associated Microbiome Communities.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37546903}, issn = {2692-8205}, support = {F31 DE033564/DE/NIDCR NIH HHS/United States ; I01 CX002212/CX/CSRD VA/United States ; R01 AI137075/AI/NIAID NIH HHS/United States ; T90 DE023520/DE/NIDCR NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; }, abstract = {The microbiome is a complex micro-ecosystem that provides the host with pathogen defense, food metabolism, and other vital processes. Alterations of the microbiome (dysbiosis) have been linked with a number of diseases such as cancers, multiple sclerosis (MS), Alzheimer's disease, etc. Generally, differential abundance testing between the healthy and patient groups is performed to identify important bacteria (enriched or depleted in one group). However, simply providing a singular species of bacteria to an individual lacking that species for health improvement has not been as successful as fecal matter transplant (FMT) therapy. Interestingly, FMT therapy transfers the entire gut microbiome of a healthy (or mixture of) individual to an individual with a disease. FMTs do, however, have limited success, possibly due to concerns that not all bacteria in the community may be responsible for the healthy phenotype. Therefore, it is important to identify the community of microorganisms linked to the health as well as the disease state of the host. Here we applied topic modeling, a natural language processing tool, to assess latent interactions occurring among microbes; thus, providing a representation of the community of bacteria relevant to healthy vs. disease state. Specifically, we utilized our previously published data that studied the gut microbiome of patients with relapsing-remitting MS (RRMS), a neurodegenerative autoimmune disease that has been linked to a variety of factors, including a dysbiotic gut microbiome. With topic modeling we identified communities of bacteria associated with RRMS, including genera previously discovered, but also other taxa that would have been overlooked simply with differential abundance testing. Our work shows that topic modeling can be a useful tool for analyzing the microbiome in dysbiosis and that it could be considered along with the commonly utilized differential abundance tests to better understand the role of the gut microbiome in health and disease.}, }
@article {pmid37545638, year = {2023}, author = {Maslennikov, R and Alieva, A and Poluektova, E and Zharikov, Y and Suslov, A and Letyagina, Y and Vasileva, E and Levshina, A and Kozlov, E and Ivashkin, V}, title = {Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota.}, journal = {World journal of gastroenterology}, volume = {29}, number = {27}, pages = {4236-4251}, pmid = {37545638}, issn = {2219-2840}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; *Sarcopenia/etiology/therapy ; Liver Cirrhosis/complications/therapy/microbiology ; }, abstract = {Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.}, }
@article {pmid37545398, year = {2023}, author = {Huang, W and Chen, H and He, Q and Xie, W and Peng, Z and Ma, Q and Huang, Q and Chen, Z and Liu, Y}, title = {Nobiletin protects against ferroptosis to alleviate sepsis-associated acute liver injury by modulating the gut microbiota.}, journal = {Food &amp; function}, volume = {14}, number = {16}, pages = {7692-7704}, doi = {10.1039/d3fo01684f}, pmid = {37545398}, issn = {2042-650X}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; *Ferroptosis ; NF-E2-Related Factor 2/genetics/metabolism ; RNA, Ribosomal, 16S ; *Sepsis/complications/drug therapy/metabolism ; Liver/metabolism ; }, abstract = {Nobiletin (NOB), a plant-based polymethoxyflavone, is a promising protective agent against sepsis; yet the mechanisms were not fully elucidated. The gut microbiota is found to be strongly associated with sepsis-associated acute liver injury (SALI). Here, our study aimed to evaluate the protective effect of NOB on SALI and explore the underlying molecular mechanisms. Cecal ligation and puncture (CLP) was used to induce SALI in mice. NOB was administered by gavage for 7 days before CLP induction. The 16S rRNA gene sequencing and fecal microbiota transplantation (FMT) were performed to verify the function of the gut microbiota. The markers of ferroptosis, inflammation, gut microbiota composition, and liver injury were determined. NOB administration significantly alleviated hepatic ferroptosis and inflammation in septic mice. Meanwhile, NOB upregulated the expression levels of nuclear factor E2-related factor 2 (Nrf2) and its downstream protein heme oxygenase-1 (HO-1). The protective effect of NOB administration against ferroptosis in SALI mice was reversed by the Nrf2 inhibitor ML385. Additionally, increased abundances of Ligilactobacillus, Akkermansia, and Lactobacillus, and decreased abundances of Dubosiella and Bacteroides in the gut were observed under NOB administration, suggesting that NOB might modulate the gut microbiota composition of septic mice. Furthermore, gut microbiota ablation by antibiotic treatment partly reversed the protective effects of NOB on sepsis. FMT also confirmed that NOB inhibited ferroptosis and activated Nrf2 signalling in SALI mice by modulating the gut microbiota. These results revealed that, by modulating the gut microbiota, NOB attenuated ferroptosis in septic liver injury through upregulating Nrf2-Gpx4. Our findings provide novel insights into microbiome-based therapeutic approaches for sepsis.}, }
@article {pmid37542273, year = {2023}, author = {Weng, S and Huang, L and Cai, B and He, L and Wen, S and Li, J and Zhong, Z and Zhang, H and Huang, C and Yang, Y and Jiang, Q and Liu, F}, title = {Astragaloside IV ameliorates experimental autoimmune myasthenia gravis by regulating CD4 + T cells and altering gut microbiota.}, journal = {Chinese medicine}, volume = {18}, number = {1}, pages = {97}, pmid = {37542273}, issn = {1749-8546}, support = {81904133//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 2019QN28//First Affiliated Hospital of Zhengzhou University/ ; 202102080136//Guangzhou Municipal Science and Technology Project/ ; 2021XK18//Collaborative Innovation Center for Modern Science and Technology and Industrial Development of Jiangxi Traditional Medicine/ ; }, abstract = {BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease and its pathogenesis is closely related to CD4 + T cells. In recent years, gut microbiota is considered to play an important role in the pathogenesis of MG. Astragaloside IV (AS-IV) is one of the main active components extracted from Astragalus membranaceus and has immunomodulatory effects. To study the immunomodulatory effect of AS-IV and the changes of gut microbiota on experimental autoimmune myasthenia gravis (EAMG) mice, we explore the possible mechanism of AS-IV in improving MG.<br><br>METHODS: In this study, network pharmacology was utilized to screen the crucial targets of AS-IV in the treatment of MG. Subsequently, a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to identify potential pathways through which AS-IV acts against MG. Furthermore, experimental investigations were conducted to validate the underlying mechanism of AS-IV in MG treatment. Before modeling, 5 mice were randomly selected as the control group (CFA group), and the other 10 were induced to EAMG model. These mice were randomly divided into EAMG group and EAMG&#x2009;+&#x2009;AS-IV group, n&#x2009;=&#x2009;5/group. In EAMG&#x2009;+&#x2009;AS-IV group, AS-IV was administered by gavage. CFA and EAMG groups were given the same volume of PBS. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. At the last administration, the feces were collected for 16S RNA microbiota analysis. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected by flow cytometry. The levels of IFN-&#x3b3;, IL-17 and TGF-&#x3b2; in serum were measured by ELISA. Furthermore, fecal microbial transplantation (FMT) experiments were performed for exploring the influence of changed intestinal flora on EAMG. After EAMG model was induced, the mice were treated with antibiotics daily for 4&#xa0;weeks to germ-free. Then germ-free EAMG mice were randomly divided into two groups: FMT EAMG group, FMT AS-IV group, n&#x2009;=&#x2009;3/group. Fecal extractions from EAMG and EAMG&#x2009;+&#x2009;AS-IV groups as gathered above were used to administered daily to the respective groups for 4&#xa0;weeks. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected at the last administration. The levels of IFN-&#x3b3;, IL-17 and TGF-&#x3b2; in serum were measured by ELISA.<br><br>RESULTS: The network pharmacology and KEGG pathway analysis revealed that AS-IV regulates T cell pathways, including T cell receptor signaling pathway and Th17 cell differentiation, suggesting its potential in improving MG. Further experimental verification demonstrated that AS-IV administration improved muscle strength and body weight, reduced the level of Th1 and Th17 cells, enhanced the level of Treg cells, and resulted in alterations of the gut microbiota, including changes in beta diversity, the Firmicutes/Bacteroidetes (F/B) ratio, and the abundance of Clostridia in EAMG mice. We further conducted FMT tests and demonstrated that the EAMG Abx-treated mice which were transplanted the feces of mice treated with AS-IV significantly alleviated myasthenia symptoms, reduced Th1 and Th17 cells levels, and increased Treg cell levels.<br><br>CONCLUSION: This study speculated that AS-IV ameliorates EAMG by regulating CD4&#x2009;+&#x2009;T cells and altering the structure and species of gut microbiota of EAMG.}, }
@article {pmid37540090, year = {2023}, author = {McChalicher, CWJ and Lombardo, MJ and Khanna, S and McKenzie, GJ and Halvorsen, EM and Almomani, S and Schuster, B and Hasson, BR and McGovern, BH and Ege, DS and Auniņš, JG}, title = {Manufacturing Processes of a Purified Microbiome Therapeutic Reduce Risk of Transmission of Potential Bacterial Pathogens in Donor Stool.}, journal = {The Journal of infectious diseases}, volume = {228}, number = {10}, pages = {1452-1455}, pmid = {37540090}, issn = {1537-6613}, mesh = {Humans ; *Clostridioides difficile ; *Gastrointestinal Microbiome ; Feces/microbiology ; Fecal Microbiota Transplantation ; *Microbiota ; *Clostridium Infections/prevention &amp; control/microbiology ; Recurrence ; }, abstract = {BACKGROUND: Although fecal microbiota transplant has been used to prevent recurrent Clostridioides difficile infection (rCDI), documented pathogen transmissions highlight inherent safety risks of minimally processed stool. We describe manufacturing processes for fecal microbiota spores, live (VOWST; VOS, formerly SER-109), a microbiota-based oral therapeutic of Firmicutes spores.<br><br>METHODS: Bacterial inactivation kill curves were obtained after ethanol exposure for 4 model organisms spiked into process intermediates.<br><br>RESULTS: Bacterial log reduction factors ranged from 6.5 log10 to 7.4 log10 and lysis of spiked organisms occurred rapidly within 30 seconds.<br><br>CONCLUSIONS: These experiments demonstrate substantial and rapid inactivation of representative organisms, supporting the potential benefit of VOS manufacturing processes to mitigate risk.}, }
@article {pmid37537245, year = {2023}, author = {Scott, AP and Henden, A and Kennedy, GA and Tey, SK}, title = {PET assessment of acute gastrointestinal graft versus host disease.}, journal = {Bone marrow transplantation}, volume = {58}, number = {9}, pages = {973-979}, pmid = {37537245}, issn = {1476-5365}, mesh = {Humans ; *Graft vs Host Disease/diagnostic imaging/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Gastrointestinal Tract/diagnostic imaging ; Positron-Emission Tomography/adverse effects ; Biopsy/adverse effects ; Acute Disease ; *Gastrointestinal Diseases/diagnostic imaging/etiology ; }, abstract = {Acute gastrointestinal graft versus host disease (GI-GVHD) is a common complication following allogeneic haematopoietic cell transplantation (HCT), and is characterised by severe morbidity, frequent treatment-refractoriness, and high mortality. Early, accurate identification of GI-GVHD could allow for therapeutic interventions to ameliorate its severity, improve response rates and survival; however, standard endoscopic biopsy is inadequately informative in terms of diagnostic sensitivity or outcome prediction. In an era where rapid technological and laboratory advances have dramatically expanded our understanding of GI-GVHD biology and potential therapeutic targets, there is substantial scope for novel investigations that can precisely guide GI-GVHD management. In particular, the combination of tissue-based biomarker assessment (plasma cytokines, faecal microbiome) and molecular imaging by positron emission tomography (PET) offers the potential for non-invasive, real-time in vivo assessment of donor:recipient immune activity within the GI tract for GI-GVHD prediction or diagnosis. In this article, we review the evidence regarding GI-GVHD diagnosis, and examine the potential roles and translational opportunities posed by these novel diagnostic tools, with a focus on the evolving role of PET.}, }
@article {pmid37537181, year = {2023}, author = {Wu, Q and Boonma, P and Badu, S and Yalcinkaya, N and So, SY and Garey, KW and Williams, K and Arnold, LE and Shulman, RJ and Kellermayer, R and Savidge, TC}, title = {Donor-recipient specificity and age-dependency in fecal microbiota therapy and probiotic resolution of gastrointestinal symptoms.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {54}, pmid = {37537181}, issn = {2055-5008}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 DK130517/DK/NIDDK NIH HHS/United States ; R01 NR005337/NR/NINR NIH HHS/United States ; }, mesh = {Adult ; Humans ; Child ; *Autism Spectrum Disorder ; *Clostridioides difficile ; Feces ; Fecal Microbiota Transplantation ; *Microbiota ; *Clostridium Infections/therapy ; }, abstract = {Fecal microbiota transplantation (FMT) has proven to be an effective treatment for recurrent Clostridioides difficile infection (rCDI) in both adult and pediatric patients. However, as microbiome development is a critical factor in children, it remains unclear whether adult fecal donors can provide age-appropriate functional restoration in pediatric patients. To address this issue, we conducted an integrated systems approach and found that concordant donor strain engraftment, along with metabolite restoration, are associated with FMT outcomes in both adult and pediatric rCDI patients. Although functional restoration after FMT is not strain-specific, specialized metabolic functions are retained in pediatric patients when adult fecal donors are used. Furthermore, we demonstrated broad utility of high-resolution variant-calling by linking probiotic-strain engraftment with improved gastrointestinal symptoms in adults with irritable bowel syndrome and in children with autism spectrum disorder. Our findings emphasize the importance of strain-level identification when assessing the efficacy of probiotics and microbiota-based therapeutics.}, }
@article {pmid37536860, year = {2023}, author = {Hyoju, S and Machutta, K and Krezalek, MA and Alverdy, JC}, title = {What Is the Role of the Gut in Wound Infections?.}, journal = {Advances in surgery}, volume = {57}, number = {1}, pages = {31-46}, pmid = {37536860}, issn = {1878-0555}, support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Surgical Wound Infection/prevention &amp; control ; *Gastrointestinal Microbiome ; }, abstract = {Emerging evidence suggest a major role for the gut microbiome in wound infections. A Trojan Horse mechanism of surgical site infections has been hypothesized to occur when pathogens in the gut, gums, and periodontal areas enter an immune cell and silently travel to the wound site where they release their infectious payload. Genetic tracking of microbes at the strain level is now possible with genetic sequencing techniques and can clarify the origin of microbes that cause wound infections. An emerging field of dietary prehabilitation to modulate the microbiome before surgery is being described to improve infection-related outcomes from surgery.}, }
@article {pmid37536616, year = {2023}, author = {Gupta, U and Dey, P}, title = {Rise of the guardians: Gut microbial maneuvers in bacterial infections.}, journal = {Life sciences}, volume = {330}, number = {}, pages = {121993}, doi = {10.1016/j.lfs.2023.121993}, pmid = {37536616}, issn = {1879-0631}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Bacterial Infections/drug therapy ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; *Probiotics ; }, abstract = {AIMS: Bacterial infections are one of the major causes of mortality globally. The gut microbiota, primarily comprised of the commensals, performs an important role in maintaining intestinal immunometabolic homeostasis. The current review aims to provide a comprehensive understanding of how modulation of the gut microbiota influences opportunistic bacterial infections.<br><br>MATERIALS AND METHODS: Primarily centered around mechanisms related to colonization resistance, nutrient, and metabolite-associated factors, mucosal immune response, and commensal-pathogen reciprocal interactions, we discuss how gut microbiota can promote or prevent bacterial infections.<br><br>KEY FINDINGS: Opportunistic infections can occur directly due to obligate pathogens or indirectly due to the overgrowth of opportunistic pathobionts. Gut microbiota-centered mechanisms of altered intestinal immunometabolic and metabolomic homeostasis play a significant role in infection promotion and prevention. Depletion in the population of commensals, increased abundance of pathobionts, and overall decrease in gut microbial diversity and richness caused due to prolonged antibiotic use are risk factors of opportunistic bacterial infections, including infections from multidrug-resistant spp. Gut commensals can limit opportunistic infections by mechanisms including the production of antimicrobials, short-chain fatty acids, bile acid metabolism, promoting mucin formation, and maintaining immunological balance at the mucosa. Gut microbiota-centered strategies, including the administration of probiotics and fecal microbiota transplantation, could help attenuate opportunistic bacterial infections.<br><br>SIGNIFICANCE: The current review discussed the gut microbial population and function-specific aspects contributing to bacterial infection susceptibility and prophylaxis. Collectively, this review provides a comprehensive understanding of the mechanisms related to the dual role of gut microbiota in bacterial infections.}, }
@article {pmid37536115, year = {2023}, author = {Vagaggini, C and Brai, A and Bonente, D and Lombardi, J and Poggialini, F and Pasqualini, C and Barone, V and Nicoletti, C and Bertelli, E and Dreassi, E}, title = {Development and validation of derivatization-based LC-MS/MS method for quantification of short-chain fatty acids in human, rat, and mouse plasma.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {235}, number = {}, pages = {115599}, doi = {10.1016/j.jpba.2023.115599}, pmid = {37536115}, issn = {1873-264X}, mesh = {Mice ; Rats ; Humans ; Animals ; Aged ; Chromatography, Liquid/methods ; *Tandem Mass Spectrometry/methods ; Feces/chemistry ; Fatty Acids, Volatile/analysis ; *Gastrointestinal Microbiome ; }, abstract = {Short-chain fatty acids (SCFAs), the end products of gut microbial fermentation of dietary fibers and non-digestible polysaccharides, act as a link between the microbiome, immune system, and inflammatory processes. The importance of accurately quantifying SCFAs in plasma has recently emerged to understand their biological role. In this work, a sensitive and reproducible LC-MS/MS method is reported for SCFAs quantification in three different matrices such as human, rat and mouse plasma via derivatization, using as derivatizing agent O-benzylhydroxylamine (O-BHA), coupled with liquid-liquid extraction. First, the instrumental parameters of the mass spectrometer and then the chromatographic conditions were optimized using previously SCFAs derivatives synthetized and used as standards. After that, the best conditions for derivatization and extraction from plasma were studied and a series of determinations were performed on human, rat, and mouse plasma aliquots to validate the overall method (derivatization, extraction, and LC-MS/MS determination). The method showed good performance in terms of recovery (> 80%), precision (RSD <14%), accuracy (RE < ± 10%) and sensitivity (LOQ of 0.01 µM for acetic, butyric, propionic and isobutyric acid) in all plasma samples. The method thus developed and validated was applied to the quantification of major SCFAs in adult and aged mice, germ-free mice and in germ-free recipient mice subjected to fecal transplant from adult and aged donors. Results highlighted how plasma concentrations of SCFAs are correlated with age further highlighting the importance of developing a method that is reliable for the quantification of SCFAs to study their biological role.}, }
@article {pmid37534844, year = {2023}, author = {Halue, G and Tharapanich, H and Phannajit, J and Kanjanabuch, T and Banjongjit, A and Lorvinitnun, P and Sritippayawan, S and Sopassathit, W and Poonvivatchaikarn, U and Buranaosot, S and Somboonsilp, W and Wongtrakul, P and Boonyakrai, C and Narenpitak, S and Tatiyanupanwong, S and Saikong, W and Uppamai, S and Panyatong, S and Chieochanthanakij, R and Lounseng, N and Wongpiang, A and Treamtrakanpon, W and Rattanasoonton, P and Lukrat, N and Songviriyavithaya, P and Parinyasiri, U and Rojsanga, P and Kanjanabuch, P and Puapatanakul, P and Pongpirul, K and Johnson, DW and Perl, J and Pecoits-Filho, R and Ophascharoensuk, V and Tungsanga, K and , }, title = {Constipation and clinical outcomes in peritoneal dialysis: Results from Thailand PDOPPS.}, journal = {Nephrology (Carlton, Vic.)}, volume = {28 Suppl 1}, number = {}, pages = {35-47}, doi = {10.1111/nep.14224}, pmid = {37534844}, issn = {1440-1797}, mesh = {Humans ; Thailand/epidemiology ; *Peritoneal Dialysis/methods ; Renal Dialysis/adverse effects ; Constipation/diagnosis/epidemiology/therapy ; *Peritonitis/diagnosis/epidemiology/etiology ; *Kidney Failure, Chronic/diagnosis/therapy/complications ; }, abstract = {BACKGROUND: Patient-reported outcome measures (PROMs) are widely recognized as valuable predictors of clinical outcomes in peritoneal dialysis (PD). Our study aimed to explore the connections between patient-reported constipation and clinical outcomes.<br><br>METHODS: We assessed constipation in patients across 22 facilities participating in the Thailand Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014 to 2017. Constipation diagnosis utilized objective assessment tools such as the Bristol stool form scale (BSFS) and a self-reported questionnaire known as the constipation severity score (CSS). The BSFS is a 7-level scale that visually inspects feces based on texture and morphology, while the CSS measures constipation duration and severity using a 5-point Likert scale for various factors. We employed Cox proportional hazards model regression to determine the associations between constipation and clinical outcomes, including mortality, hemodialysis (HD) transfer and peritonitis.<br><br>RESULTS: Among 975 randomly selected PD patients from 22 facilities, 845 provided written informed consent, and 729 completed CSS questionnaire. Constipation was prevalent in the PD population (13%), particularly among older patients, those who were caregiver dependent, had diabetes and poorer nutritional status (indicated by lower time-averaged serum albumin, potassium, creatinine and phosphate concentrations). Twenty-seven percent of which experiencing symptoms of constipation for over a year. Notably, self-reported constipation at baseline was significantly associated with a shorter time to first peritonitis and higher rates of peritonitis and death. However, no significant association was found between constipation and HD transfer after adjusting for various factors, including age, gender, PD vintage, comorbidities, shared frailty by study sites and serum albumin.<br><br>CONCLUSION: Patient-reported constipation independently correlated with increased risks of peritonitis and all-cause mortality, though no such correlation was observed with HD transfer. These findings underscore the need for further investigation to identify effective interventions for constipation in PD patients.}, }
@article {pmid37533870, year = {2023}, author = {Yao, K and Xie, Y and Wang, J and Lin, Y and Chen, X and Zhou, T}, title = {Gut microbiota: a newly identified environmental factor in systemic lupus erythematosus.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1202850}, pmid = {37533870}, issn = {1664-3224}, mesh = {Humans ; Female ; *Gastrointestinal Microbiome ; *Lupus Erythematosus, Systemic/therapy/complications ; Autoimmunity ; Fecal Microbiota Transplantation/adverse effects ; *Probiotics/therapeutic use ; }, abstract = {Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age and is characterized by the damage to multiple target organs. The pathogenesis of SLE is complex, and its etiology mainly involves genetic and environmental factors. At present, there is still a lack of effective means to cure SLE. In recent years, growing evidence has shown that gut microbiota, as an environmental factor, triggers autoimmunity through potential mechanisms including translocation and molecular mimicry, leads to immune dysregulation, and contributes to the development of SLE. Dietary intervention, drug therapy, probiotics supplement, fecal microbiome transplantation and other ways to modulate gut microbiota appear to be a potential treatment for SLE. In this review, the dysbiosis of gut microbiota in SLE, potential mechanisms linking gut microbiota and SLE, and immune dysregulation associated with gut microbiota in SLE are summarized.}, }
@article {pmid37533828, year = {2023}, author = {Zhang, P and Chen, J and Ming, Y and Niu, Y}, title = {Probiotics treatment ameliorated mycophenolic acid-induced colitis by enhancing intestinal barrier function and improving intestinal microbiota dysbiosis in mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1153188}, pmid = {37533828}, issn = {1664-302X}, abstract = {BACKGROUND: Mycophenolic acid (MPA)-induced colitis was still a severe side effect and challenge faced by solid transplant recipients. We aimed to explore the function and mechanism of probiotics in the treatment of MPA-induced colitis.<br><br>METHODS: In this study, 15 mice (C57BL/6) were randomly assigned into three groups: control (CNTL) group (n =&#x2009;5), MPA group (n =&#x2009;5) and the MPA&#x2009;+&#x2009;Probiotic group (n =&#x2009;5). Bifid Triple Viable capsules, which were drugs for clinical use and consisted of Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis, were used in Probiotic group. Body weight change, stool scores, colon histopathology and morphology were used to evaluate the disease severity. The intestinal mucosal barrier function was assessed by measuring the expression level of secretory immunoglobulin A (sIgA), Zonula occludens-1 (ZO-1) and Occludin. Finally, 16S rDNA sequencing and bioinformatics analysis were performed on mice feces to compare the different intestinal microbial composition and diversity among three groups.<br><br>RESULTS: Compared with the CNTL group, the mice in MPA group showed a significantly decreased body weight, increased stool scores, shortened colon length and severe colon inflammation. However, probiotics treated MPA mice reversed the disease severity, indicating that probiotics ameliorated MPA-induced colitis in mice. Mechanistically, probiotics improved the intestinal barrier function by up-regulating the expression of sIgA, ZO-1 and Occludin. Moreover, MPA-induced colitis led to intestinal microbiota dysbiosis, including the change of Firmicutes/Bacteroidetes ratio, &#x3b1;- and &#x3b2;-diversity. But probiotic treated group showed mild change in these microbial features. Additionally, we found that Clostridiales was the most significantly different microbiota flora in MPA group.<br><br>CONCLUSION: Probiotics treatment ameliorated MPA-induced colitis by enhancing intestinal barrier function and improving intestinal microbiota dysbiosis. Clostridiales might be the dominant functional intestinal microflora and serve as the potential therapy target in MPA-induced colitis.}, }
@article {pmid37533076, year = {2023}, author = {Yang, X and Li, D and Zhang, M and Feng, Y and Jin, X and Liu, D and Guo, Y and Hu, Y}, title = {Ginkgo biloba extract alleviates fatty liver hemorrhagic syndrome in laying hens via reshaping gut microbiota.}, journal = {Journal of animal science and biotechnology}, volume = {14}, number = {1}, pages = {97}, pmid = {37533076}, issn = {1674-9782}, support = {2022YFA1304201//National Key Research and Development Program of China/ ; 6222032//Natural Science Foundation of Beijing Municipality/ ; }, abstract = {BACKGROUND: Ginkgo biloba extract (GBE) is evidenced to be effective in the prevention and alleviation of metabolic disorders, including obesity, diabetes and fatty liver disease. However, the role of GBE in alleviating fatty liver hemorrhagic syndrome (FLHS) in laying hens and the underlying mechanisms remain to be elucidated. Here, we investigated the effects of GBE on relieving FLHS with an emphasis on the modulatory role of GBE in chicken gut microbiota.<br><br>RESULTS: The results showed that GBE treatment ameliorated biochemical blood indicators in high-fat diet (HFD)-induced FLHS laying hen model by decreasing the levels of TG, TC, ALT and ALP. The lipid accumulation and pathological score of liver were also relieved after GBE treatment. Moreover, GBE treatment enhanced the antioxidant activity of liver and serum by increasing GSH, SOD, T-AOC, GSH-PX and reducing MDA, and downregulated the expression of genes related to lipid synthesis (FAS, LXR&#x3b1;, GPAT1, PPAR&#x3b3; and ChREBP1) and inflammatory cytokines (TNF-&#x3b1;, IL-6, TLR4 and NF-&#x3ba;B) in the liver. Microbial profiling analysis revealed that GBE treatment reshaped the HFD-perturbed gut microbiota, particularly elevated the abundance of Megasphaera in the cecum. Meanwhile, targeted metabolomic analysis of SCFAs revealed that GBE treatment significantly promoted the production of total SCFAs, acetate and propionate, which were positively correlated with the GBE-enriched gut microbiota. Finally, we confirmed that the GBE-altered gut microbiota was sufficient to alleviate FLHS by fecal microbiota transplantation (FMT).<br><br>CONCLUSIONS: We provided evidence that GBE alleviated FLHS in HFD-induced laying hens through reshaping the composition of gut microbiota. Our findings shed light on mechanism underlying the anti-FLHS efficacy of GBE and lay foundations for future use of GBE as additive to prevent and control FLHS in laying hen industry.}, }
@article {pmid37527781, year = {2023}, author = {Ranjbarian, T and Schnabl, B}, title = {Gut Microbiome-Centered Therapies for Alcohol-Associated Liver Disease.}, journal = {Seminars in liver disease}, volume = {43}, number = {3}, pages = {311-322}, doi = {10.1055/a-2145-7331}, pmid = {37527781}, issn = {1098-8971}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Liver Diseases, Alcoholic/therapy ; Liver ; Ethanol/therapeutic use ; *Fatty Liver ; *Liver Neoplasms/complications ; Dysbiosis/complications ; }, abstract = {Globally, liver disease caused by alcohol is becoming more prevalent each year. Misuse of alcohol causes a spectrum of liver diseases, such as liver steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The cornerstone of treatment is abstinence from alcohol. In spite of this, available treatment for alcohol-associated liver disease (ALD) shows limited effectiveness currently. There are numerous ways in which alcohol disrupts the gut-liver axis, including dysbiosis of the gut microbiome, disruption of mucus and epithelial cell barriers, impaired production of antimicrobial molecules, and dysfunction of the immune system, causing translocation of viable microbes and microbial products to the liver and systemic circulation. Microbial exposure results in not only inflammation and progression of liver disease but also infections in late-stage ALD. This led scientists to focus their therapeutic strategies and targets for ALD on the gut microbiome. Throughout this review, we address the role of gut microbiome-centered therapeutic approaches for ALD focusing predominantly on randomized controlled trials. We will summarize the latest clinical trials using probiotics, antibiotics, and fecal microbial transplants in modulating the gut-liver axis and for improvement of ALD.}, }
@article {pmid37527604, year = {2023}, author = {Yi, X and Cai, R and Shaoyong, W and Wang, G and Yan, W and He, Z and Li, R and Chao, M and Zhao, T and Deng, L and Yang, G and Pang, W}, title = {Melatonin promotes gut anti-oxidative status in perinatal rat by remodeling the gut microbiome.}, journal = {Redox biology}, volume = {65}, number = {}, pages = {102829}, pmid = {37527604}, issn = {2213-2317}, mesh = {Female ; Rats ; Animals ; *Gastrointestinal Microbiome ; *Melatonin/pharmacology ; Fecal Microbiota Transplantation/methods ; Inflammation ; Mammals ; }, abstract = {Gut health is important for nutrition absorption, reproduction, and lactation in perinatal and early weaned mammals. Although melatonin functions in maintaining circadian rhythms and preventing obesity, neurodegenerative diseases, and viral infections, its impact on the gut microbiome and its function in mediating gut health through gut microbiota remain largely unexplored. In the present study, the microbiome of rats was monitoring after fecal microbiota transplantation (FMT) and foster care (FC). The results showed that FMT and FC increased intestinal villus height/crypt depth in perinatal rats. Mechanistically, the melatonin-mediated remodeling of gut microbiota inhibited oxidative stress, which led to attenuation of autophagy and inflammation. In addition, FMT and FC encouraged the growth of more beneficial intestinal bacteria, such as Allobaculum, Bifidobacterium, and Faecalibaculum, which produce more short-chain fatty acids to strengthen intestinal anti-oxidation. These findings suggest that melatonin-treated gut microbiota increase the production of SCFAs, which improve gut health by reducing oxidative stress, autophagy and inflammation. The transfer of melatonin-treated gut microbiota may be a new and effective method by which to ameliorate gut health in perinatal and weaned mammals.}, }
@article {pmid37527003, year = {2023}, author = {Puerta-Alcalde, P and Garcia-Vidal, C and Soriano, A}, title = {Prevention and treatment of C. difficile in cancer patients.}, journal = {Current opinion in infectious diseases}, volume = {36}, number = {6}, pages = {473-480}, pmid = {37527003}, issn = {1473-6527}, mesh = {Humans ; *Clostridioides difficile ; Neoplasm Recurrence, Local/chemically induced/drug therapy ; Anti-Bacterial Agents ; Fidaxomicin ; *Clostridium Infections/prevention &amp; control ; }, abstract = {PURPOSE OF REVIEW: We provide an update on the recent literature on Clostridioides difficile infection (CDI) in cancer patients.<br><br>RECENT FINDINGS: Distinguishing between colonization and infection remains challenging in cancer patients. Many patients with negative toxin analysis are still treated for CDI, and some meet criteria for severe cases. The incidence of CDI is high in cancer patients, especially those with haematological malignancies. Disruption of the gut microbiome due to antibiotic consumption, chemotherapy and radiotherapy is the primary factor contributing to CDI development. The severity of CDI in cancer patients is often unclear due to the absence of well-defined severity criteria. Certain microbiome species predominance and specific ribotypes have been associated with worse outcomes. Whole genome sequencing could be helpful for differentiating recurrence from reinfection and exploring potential nosocomial transmission. While certain new drugs such as fidaxomicin or bezlotoxumab show promise, the optimal treatment and prevention strategies for CDI in cancer patients remain uncertain. Faecal microbiota transplantation (FMT) holds potential for reducing CDI recurrence rates.<br><br>SUMMARY: Further studies are needed to provide robust recommendations for diagnosis, grading severity, and therapeutic management of CDI in cancer patients. Recurrences are particularly concerning due to subsequent exposition to CDI risk factors.}, }
@article {pmid37524154, year = {2023}, author = {Yan, J and Duan, W and Gao, Q and Mao, T and Wang, M and Duan, J and Li, J}, title = {ENPP2 inhibitor improves proliferation in AOM/DSS-induced colorectal cancer mice via remodeling the gut barrier function and gut microbiota composition.}, journal = {Pharmacological research}, volume = {195}, number = {}, pages = {106877}, doi = {10.1016/j.phrs.2023.106877}, pmid = {37524154}, issn = {1096-1186}, mesh = {Animals ; Mice ; Azoxymethane/adverse effects ; Cell Proliferation ; Colitis/chemically induced ; *Colorectal Neoplasms/drug therapy/metabolism ; Dextran Sulfate/pharmacology ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; *Phosphoric Diester Hydrolases/metabolism ; }, abstract = {In our previous multicenter study, we delineated the inherent metabolic features of colorectal cancer (CRC). Therein, we identified a member of the ectonucleotide pyrophosphatase/ phosphodiesterase family (ENPP2) as a significant differential metabolite of CRC. In this study, the role of ENPP2 in CRC has been demonstrated using established in vitro and in vivo models including ENPP2 gene knockdown, and use of the ENPP2 inhibitor, GLPG1690. We found that CRC proliferation was decreased after either ENPP2 gene knockdown or use of ENPP2 inhibitors. We further evaluated the role of GLPG1690 in AOM/DSS-induced CRC mice via intestinal barrier function, macrophage polarization, inflammatory response and microbial homeostasis. Results of immunofluorescence staining and Western blotting showed that GLPG1690 can restore gut-barrier function by increasing the expression of tight junction proteins, claudin-1, occludin and ZO-1. M2 tumor-associated macrophage polarization and colonic inflammation were attenuated after treatment with GLPG1690 using the Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) model. Moreover, 16 S rDNA pyrosequencing and metagenomic analysis showed that GLPG1690 could alleviate gut dysbiosis in mice. Furthermore, administration of GLPG1690 with antibiotics as well as fecal microbiota transplantation assays demonstrated a close link between the efficacy of GLPG1690 and the gut microbiota composition. Finally, results of metabolomic analysis implicated mainly the gut microbiota-derived metabolites of aromatic amino acids in CRC progression. These findings may provide novel insights into the development of small-molecule ENPP2 inhibitors for the treatment of CRC.}, }
@article {pmid37523293, year = {2023}, author = {Maigoro, AY and Muhammad, M and Bello, B and Useh, U and Lee, S}, title = {Exploration of Gut Microbiome Research in Africa: A Scoping Review.}, journal = {Journal of medicinal food}, volume = {26}, number = {9}, pages = {616-623}, doi = {10.1089/jmf.2023.K.0005}, pmid = {37523293}, issn = {1557-7600}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota ; Africa ; Dietary Supplements ; }, abstract = {The crucial role of the gut microbiome in various diseases has led to increased interest in interventions and therapeutics targeting the human microbiome. Accordingly, the current scoping review analyzed the diseases and interventions involved in gut microbiome research in Africa. The electronic databases of PubMed, Google Scholar, and Scopus were searched from inception to October 2021. This study identified 48 studies involving 7073 study participants. Of the 48 studies, 20 (42%) used interventions to modulate gut microbiota, whereas the remaining 28 (58%) did not. Out of the total African countries, only 13% were involved in intervention-based gut microbiome research, whereas a larger proportion of 67% were not involved in any gut microbiome research. The interventions used in gut microbiome research in Africa include supplements, natural products, educational approaches, associated pathogens, albendazole, fresh daily yogurt, iron-containing lipid-based nutrient supplements, fecal microbiota transplant, and prophylactic cotrimoxazole. This scoping review highlights the current state of gut microbiome research in Africa. The findings of this review can inform the design of future studies and interventions aimed at improving gut health in African populations.}, }
@article {pmid37521153, year = {2023}, author = {Alfuzaie, R}, title = {The Link Between Gastrointestinal Microbiome and Ocular Disorders.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {17}, number = {}, pages = {2133-2140}, pmid = {37521153}, issn = {1177-5467}, abstract = {The gut-eye axis has been hypothesized to be a factor in many eye pathologies. This review examines papers from PubMed about this topic. Bacterial commensals could either be protective by regulating the immune system or prove to be damaging to the gut mucosal wall and incite an inflammatory process. The balance between the two appears to be crucial in maintaining eye health. Imbalances have been implicated in ophthalmologic conditions. The use of probiotics, dietary modifications, antibiotics, and faecal microbiota transplant in mice with pathologies such as those encountered in our practice appears to reverse disease course or at least prevent its progression. Clinical trials are currently underway to investigate their clinical significance in diseased patients.}, }
@article {pmid37518975, year = {2023}, author = {Van Jacobs, A and Williams, MD and Ralph, OG and Becerra, AZ and Chan, EY and Olaitan, O}, title = {Pancreatic Exocrine Secretion and Weight Gain After Pancreas Transplantation.}, journal = {Progress in transplantation (Aliso Viejo, Calif.)}, volume = {33}, number = {3}, pages = {236-241}, doi = {10.1177/15269248231189877}, pmid = {37518975}, issn = {2164-6708}, mesh = {Humans ; *Pancreas Transplantation ; C-Peptide ; Pancreas ; Weight Gain ; Pancreatic Elastase ; }, abstract = {INTRODUCTION: Weight gain after pancreas transplant is a poorly understood phenomenon thought to be related to increased posttransplant insulin production, immunosuppressive medications, and appetite changes. No study has investigated the effect of increased exocrine secretion posttransplant.<br><br>AIMS AND HYPOTHESIS: We hypothesized that exocrine function, measured by fecal elastase-1 (FE-1), was normal posttransplant and not correlated with weight gain. Our primary aim was to investigate changes in FE-1 levels with pancreas transplantation and to correlate this with weight gain. Establishing weight trends and identifying additional correlating factors were secondary aims.<br><br>DESIGN: Forty-two patients that underwent simultaneous pancreas and kidney or pancreas after kidney transplant at a single center between 2013 and 2021 were included. Fecal elastase was measured prospectively in each patient at a single time point, with >500&#x2005;&#xb5;g/g categorized as high. Weight and C-peptide values were obtained. All the patients were on steroid-free immunosuppression.<br><br>RESULTS: Nineteen patients (45%) had fecal elastase levels >500&#x2005;&#xb5;g/g, with a maximum of 3910&#x2005;&#xb5;g/g; 43% had levels greater than twice the upper limit of normal. The biggest increase in weight occurred between years 1 and 2, which continued to a median weight gain of 14% at 3 years. There was no correlation between weight gain and FE-1, pretransplant C-peptide levels, or duration of diabetes.<br><br>CONCLUSION: This study demonstrated supranormal fecal elastase levels and weight gain posttransplant; however, there was no correlation. Future study with serial FE-1 before and after transplant is needed to better assess its correlation with weight gain.}, }
@article {pmid37517290, year = {2023}, author = {Li, L and Yang, J and Liu, T and Shi, Y}, title = {Role of the gut-microbiota-metabolite-brain axis in the pathogenesis of preterm brain injury.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {165}, number = {}, pages = {115243}, doi = {10.1016/j.biopha.2023.115243}, pmid = {37517290}, issn = {1950-6007}, mesh = {Female ; Infant, Newborn ; Humans ; Infant, Premature ; *Premature Birth ; *Microbiota ; *Probiotics/therapeutic use ; *Brain Injuries/etiology ; Brain ; }, abstract = {Brain injury, a common complication in preterm infants, includes the destruction of the key structural and functional connections of the brain and causes neurodevelopmental disorders; it has high morbidity and mortality rates. The exact mechanism underlying brain injury in preterm infants is unclear. Intestinal flora plays a vital role in brain development and the maturation of the immune system in infants; however, detailed understanding of the gut microbiota-metabolite-brain axis in preterm infants is lacking. In this review, we summarise the key mechanisms by which the intestinal microbiota contribute to neurodevelopment and brain injury in preterm infants, with special emphasis on the influence of microorganisms and their metabolites on the regulation of neurocognitive development and neurodevelopmental risks related to preterm birth, infection and neonatal necrotising enterocolitis (NEC). This review provides support for the development and application of novel therapeutic strategies, including probiotics, prebiotics, synbiotics, and faecal bacteria transplantation targeting at brain injury in preterm infants.}, }
@article {pmid37516837, year = {2023}, author = {Salonen, T and Jokinen, E and Satokari, R and Lahtinen, P}, title = {Randomized, double-blinded, placebo-controlled pilot study: efficacy of faecal microbiota transplantation on chronic fatigue syndrome.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {513}, pmid = {37516837}, issn = {1479-5876}, mesh = {Humans ; Female ; Male ; Adult ; *Fatigue Syndrome, Chronic/therapy ; Fecal Microbiota Transplantation ; Pilot Projects ; Quality of Life ; Double-Blind Method ; }, abstract = {BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling illness of unknown aetiology. Disruption of gut microbiota may play a role in several neurological disorders. In this study, the effect of faecal microbiota transplantation (FMT) on fatigue severity and health-related quality of life (HRQOL) in patients with CFS was evaluated.<br><br>METHODS: Randomized, placebo-controlled pilot trial. Patients and researchers were blinded to treatment assignment. 11 patients with CFS (10 female and 1 male, mean age 42.2&#xa0;years and mean duration of CFS 6.3&#xa0;years) were randomly assigned to receive either FMT from a universal donor (n&#x2009;=&#x2009;5) or autologous FMT (n&#x2009;=&#x2009;6) via colonoscopy. Patients' HRQOL was assessed by using visual analog scale (VAS) and self-reporting questionnaires Modified Fatigue Impact Scale (MFIS), 15D and EQ-5D-3L. Patients' HRQOL was evaluated at baseline, and 1 and 6&#xa0;months after the FMT.<br><br>RESULTS: The baseline VAS scores in the FMT and placebo groups were 62.4 and 76.0 (p&#x2009;=&#x2009;0.29). 1-month scores were 60.0 and 73.7 and 6-months scores 72.8 and 69.5, respectively. Total MFIS scores in the FMT and placebo groups were 59.6 and 61.0 at the baseline (p&#x2009;=&#x2009;0.80), 53.5 and 62.0 at 1&#xa0;month and 58.6 and 56.2 at 6&#xa0;months. Compared to the baseline scores, differences at 1 and 6&#xa0;months were statistically insignificant both in VAS and in MFIS. The 15D and EQ-5D-3L profiles did not change after the FMT or placebo. FMT-related adverse events were not reported.<br><br>CONCLUSION: FMT was safe but did not relieve symptoms or improve the HRQOL of patients with CFS. Small number of study subjects limits the generalizability of these results. Trial Registration ClinicalTrials.gov Identifier NCT04158427, https://register.<br><br>CLINICALTRIALS: gov , date of registration 08/08/2019.}, }
@article {pmid37511862, year = {2023}, author = {Hu, D and Zhao, J and Zhang, H and Wang, G and Gu, Z}, title = {Fecal Microbiota Transplantation for Weight and Glycemic Control of Obesity as Well as the Associated Metabolic Diseases: Meta-Analysis and Comprehensive Assessment.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {7}, pages = {}, pmid = {37511862}, issn = {2075-1729}, abstract = {Objectives: An analysis of the weight and blood glucose management associated with fecal microbiota transplantation (FMT) as well as metabolic diseases associated with FMT was conducted by the authors in order to provide clinical recommendations regarding the treatment of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods: We searched PubMed, Embase, and the Cochrane Library for papers that were published between the creation of the database and October 2022. We reviewed research that investigated how FMT affected weight and glycemic management in cases of obesity and metabolic conditions that are related to obesity. Studies that were published more than once, lacked the entire text, included insufficient information, or were impossible to extract data from were excluded. Additionally, case reports, reviews, and systematic reviews were excluded from the analysis. In order to analyze the data, STATA 15.1 was used. Outcomes: When we combined all of our findings, we discovered that pooled outcomes showed that weight levels (WMD equals -4.77, 95%CI: -7.40~-2.14), BMI levels (WMD equals -1.59, 95%CI: -2.21~-0.97), HOMA-IR (WMD equals -0.79, 95%CI: -1.57~-0.00), and HbA1c (WMD equals -0.65, 95%CI: -0.75~-0.55) after FMT treatment were significantly lower than before treatment. However, FMT treatment may have no effect on glucose and insulin levels in obese patients at fasting and related metabolic diseases. Additionally, subgroup analysis outcomes found that FMT significantly reduced fasting blood glucose in people with diabetes. Conclusions: As a weight loss and glycemic control therapy, FMT helps to prevent and treat metabolic problems linked to obesity, and is a viable alternative to bariatric surgery for patients who do not wish to undergo the procedure.}, }
@article {pmid37511151, year = {2023}, author = {Ahn, JS and Choi, YJ and Kim, HB and Chung, HJ and Hong, ST}, title = {Identification of the Intestinal Microbes Associated with Locomotion.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511151}, issn = {1422-0067}, support = {C380300//Korea Basic Science Institute/ ; C320000//Korea Basic Science Institute/ ; C330340//Korea Basic Science Institute/ ; HV22C0171//Korea Health Industry Development Institute/Republic of Korea ; RS-2023-00224099//National Research Foundation of Korea/ ; }, mesh = {Humans ; Animals ; Mice ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Locomotion ; }, abstract = {Given the impact of the gut microbiome on human physiology and aging, it is possible that the gut microbiome may affect locomotion in the same way as the host's own genes. There is not yet any direct evidence linking the gut microbiome to locomotion, though there are some potential connections, such as regular physical activity and the immune system. In this study, we demonstrate that the gut microbiome can contribute differently to locomotion. We remodeled the original gut microbiome of mice through fecal microbiota transplantation (FMT) using human feces and compared the changes in locomotion of the same mice before and three months after FMT. We found that FMT affected locomotion in three different ways: positive, none (the same), and negative. Analysis of the phylogenesis, α-diversities, and β-diversities of the gut microbiome in the three groups showed that a more diverse group of intestinal microbes was established after FMT in each of the three groups, indicating that the human gut microbiome is more diverse than that of mice. The FMT-remodeled gut microbiome in each group was also different from each other. Fold change and linear correlation analyses identified Lacrimispora indolis, Pseudoflavonifractor phocaeensis, and Alistipes senegalensis in the gut microbiome as positive contributors to locomotion, while Sphingobacterium cibi, Prevotellamassilia timonensis, Parasutterella excrementihominis, Faecalibaculum rodentium, and Muribaculum intestinale were found to have negative effects. This study not only confirms the presence of gut microbiomes that contribute differently to locomotion, but also explains the mixed results in research on the association between the gut microbiome and locomotion.}, }
@article {pmid37511148, year = {2023}, author = {Yan, X and Bai, L and Qi, P and Lv, J and Song, X and Zhang, L}, title = {Potential Effects of Regulating Intestinal Flora on Immunotherapy for Liver Cancer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511148}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Neoplasms/therapy ; Fecal Microbiota Transplantation ; Immunotherapy ; }, abstract = {The intestinal flora plays an important role in the occurrence and development of liver cancer, affecting the efficacy and side effects of conventional antitumor therapy. Recently, immunotherapy for liver cancer has been a palliative treatment for patients with advanced liver cancer lacking surgical indications. Representative drugs include immune checkpoint inhibitors, regulators, tumor vaccines, and cellular immunotherapies. The effects of immunotherapy on liver cancer vary because of the heterogeneity of the tumors. Intestinal flora can affect the efficacy and side effects of immunotherapy for liver cancer by regulating host immunity. Therefore, applying probiotics, prebiotics, antibiotics, and fecal transplantation to interfere with the intestinal flora is expected to become an important means of assisting immunotherapy for liver cancer. This article reviews publications that discuss the relationship between intestinal flora and immunotherapy for liver cancer and further clarifies the potential relationship between intestinal flora and immunotherapy for liver cancer.}, }
@article {pmid37510327, year = {2023}, author = {Liu, P and Zhang, Y and Zhang, Z and Huang, X and Su, X and Yang, S and Xie, Y}, title = {Antibiotic-Induced Dysbiosis of the Gut Microbiota Impairs Gene Expression in Gut-Liver Axis of Mice.}, journal = {Genes}, volume = {14}, number = {7}, pages = {}, pmid = {37510327}, issn = {2073-4425}, mesh = {Mice ; Humans ; Animals ; Anti-Bacterial Agents/adverse effects ; *Gastrointestinal Microbiome ; Dysbiosis/chemically induced ; RNA, Ribosomal, 16S/genetics ; Liver/pathology ; *Microbiota ; Ascorbic Acid/pharmacology ; Gene Expression ; }, abstract = {Antibiotics can be a double-edged sword. The application of broad-spectrum antibiotics leads to the suppression of microorganisms in the human body without selective targeting, including numerous non-pathogenic microorganisms within the gut. As a result, dysbiosis of the gut microbiota can occur. The gut microbiota is a vast and intricate ecosystem that has been connected with various illnesses. Significantly, the gut and liver function in a closely coupled anatomical and physiological relationship referred to as the "gut-liver axis". Consequently, metabolites stemming from the gut microbiota migrate via the portal vein to the liver, thereby influencing gene expression and proper physiological activity within the liver. This study aimed to investigate the dysbiosis of gut microbiota ecology and the disruption of gene expression resulting from oral antibiotics and their subsequent recovery. In the experiment, mice were tube-fed neomycin (0.5 mg/mL) and ampicillin (1 mg/mL) for 21 days (ABX group) to conduct 16s rRNA sequencing. By simultaneously analyzing public datasets PRJDB6615, which utilized the same antibiotics, it was found that nearly 50% of the total microbiota abundance was attributed to the f__Lactobacillaceae family. Additionally, datasets GSE154465 and GSE159761, using the same antibiotics, were used to screen for differentially expressed genes pre-and post-antibiotic treatment. Quantitative real-time PCR was employed to evaluate gene expression levels before and after antibiotic treatment. It was discovered that oral antibiotics significantly disrupted gene expression in the gut and liver, likely due to the dysregulation of the gut microbiota ecology. Fecal microbiota transplantation (FMT) was found to be an effective method for restoring gut microbiota dysbiosis. To further enhance the restoration of gut microbiota and gene expression, an antioxidant, vitamin C, was added to the FMT process to counteract the oxidative effect of antibiotics on microorganisms. The results showed that FMTs with vitamin C were more effective in restoring gut microbiota and gene expression to the level of the fecal transplant donor.}, }
@article {pmid37509487, year = {2023}, author = {López-Villodres, JA and Escamilla, A and Mercado-Sáenz, S and Alba-Tercedor, C and Rodriguez-Perez, LM and Arranz-Salas, I and Sanchez-Varo, R and Bermúdez, D}, title = {Microbiome Alterations and Alzheimer's Disease: Modeling Strategies with Transgenic Mice.}, journal = {Biomedicines}, volume = {11}, number = {7}, pages = {}, pmid = {37509487}, issn = {2227-9059}, support = {C1 from Plan Propio//University of Malaga/ ; }, abstract = {In the last decade, the role of the microbiota-gut-brain axis has been gaining momentum in the context of many neurodegenerative and metabolic disorders, including Alzheimer's disease (AD) and diabetes, respectively. Notably, a balanced gut microbiota contributes to the epithelial intestinal barrier maintenance, modulates the host immune system, and releases neurotransmitters and/or neuroprotective short-chain fatty acids. However, dysbiosis may provoke immune dysregulation, impacting neuroinflammation through peripheral-central immune communication. Moreover, lipopolysaccharide or detrimental microbial end-products can cross the blood-brain barrier and induce or at least potentiate the neuropathological progression of AD. Thus, after repeated failure to find a cure for this dementia, a necessary paradigmatic shift towards considering AD as a systemic disorder has occurred. Here, we present an overview of the use of germ-free and/or transgenic animal models as valid tools to unravel the connection between dysbiosis, metabolic diseases, and AD, and to investigate novel therapeutical targets. Given the high impact of dietary habits, not only on the microbiota but also on other well-established AD risk factors such as diabetes or obesity, consistent changes of lifestyle along with microbiome-based therapies should be considered as complementary approaches.}, }
@article {pmid37507843, year = {2023}, author = {Zhong, HJ and Chen, WR and Lu, XJ and Hu, DX and Lin, DJ and Liu, T and Wu, L and Wu, LH and He, XX}, title = {Washed microbiota transplantation improves haemoglobin levels in anaemia of chronic disease.}, journal = {European journal of clinical investigation}, volume = {53}, number = {12}, pages = {e14072}, doi = {10.1111/eci.14072}, pmid = {37507843}, issn = {1365-2362}, support = {2021KCXTD025//the Education Department of Guangdong Province/ ; 2022B1111070006//the Guangdong Provincial Department of Science and Technology/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Butyrates ; Chronic Disease ; *Anemia/therapy ; Hemoglobins ; }, abstract = {BACKGROUND: Anaemia of chronic disease (ACD) is the second most common type of anaemia and lacks an effective treatment. Patients with anaemia are reported to have altered gut microbial profiles, which may affect erythropoiesis. Here, we investigated the gut microbial features of patients with ACD and determined whether regulating gut microbiota using washed microbiota transplantation (WMT) was effective in treating ACD.<br><br>METHODS: We compared the gut microbiota profile of patients with ACD and healthy controls, evaluated the efficacy of WMT on haematological parameters in the patients, and analysed the alterations in gut microbiota after WMT treatment.<br><br>RESULTS: Patients with ACD had lower gut microbial richness, and differences in microbial composition and function, relative to healthy controls. Additionally, the relative abundances of two butyrate-producing genera Lachnospiraceae NK4A136 group and Butyricicoccus, were positively correlated with the haemoglobin (HGB) level and lower in patients with ACD than controls. WMT significantly increased HGB levels in patients with ACD. After the first, second and third WMT rounds, normal HGB levels were restored in 27.02%, 27.78% and 36.37% (all p&#x2009;<&#x2009;.05) of patients with ACD, respectively. Moreover, WMT significantly increased the abundance of butyrate-producing genera and downregulated gut microbial functions that were upregulated in patients with ACD.<br><br>CONCLUSIONS: Patients with ACD exhibited differences in gut microbial composition and function relative to healthy controls. WMT is an effective treatment for ACD that reshapes gut microbial composition, restores butyrate-producing bacteria and regulates the functions of gut microbiota.}, }
@article {pmid37505972, year = {2023}, author = {Gao, J and Nie, R and Chang, H and Yang, W and Ren, Q}, title = {A meta-analysis of microbiome therapies for hepatic encephalopathy.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {35}, number = {9}, pages = {927-937}, doi = {10.1097/MEG.0000000000002596}, pmid = {37505972}, issn = {1473-5687}, mesh = {Humans ; Ammonia ; *Hepatic Encephalopathy/prevention &amp; control ; *Microbiota ; *Probiotics/adverse effects ; *Synbiotics ; Randomized Controlled Trials as Topic ; }, abstract = {Microbiome therapies may be reported to be effective in hepatic encephalopathy (HE). We thus did a meta-analysis of randomized controlled trials to assess the effect of microbiome therapies for HE. We systematically searched PubMed, Web of Science, EMBASE, and Cochrane Library for randomized controlled trials that compared the different treatments for HE including probiotics, symbiotics, and fecal microbiota transplant (FMT). Meta-analysis was performed to calculate pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Twenty-one studies met our inclusion criteria (N = 1746 participants). Probiotics, synbiotics and FMT significantly reversed minimal HE (MHE) (OR: 0.41, 95% CI: 0.19-0.90, P = 0.03), reduced overt HE (OHE) development (OR, 0.41; 95% CI: 0.28-0.61 P < 0.00001)and the frequency of serious adverse events(SAEs) (OR:0.14, 95% CI: 0.04-0.47, P = 0.001), meanwhile decreased ammonia levels (WMD: -9.26, 95% CI: -16.92 to -1.61; P = 0.02), NCT level (MD = -4.41, 95% CI: -0.87 to -0.22, P = 0.04) and hospitalization rates (OR, 0.38; 95% CI: 0.19-0.79, P = 0.009) compared with placebo/no treatment. Finally, we conclude that microbiome therapies were more effective in improving MHE and preventing progression to OHE, reducing the frequency of SAEs, and decreasing ammonia levels, NCT level, and hospitalization rates when compared to placebo/no treatment.}, }
@article {pmid37505920, year = {2023}, author = {Tan, J and Hu, R and Gong, J and Fang, C and Li, Y and Liu, M and He, Z and Hou, DX and Zhang, H and He, J and Wu, S}, title = {Protection against Metabolic Associated Fatty Liver Disease by Protocatechuic Acid.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2238959}, pmid = {37505920}, issn = {1949-0984}, mesh = {Mice ; Animals ; Cholesterol, LDL ; Fibroblast Growth Factor 1/metabolism/pharmacology ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; *Non-alcoholic Fatty Liver Disease/etiology ; Liver/metabolism ; Diet, High-Fat/adverse effects ; }, abstract = {Gut microbiota-diet interaction has been identified as a key factor of metabolic associated fatty liver disease (MAFLD). Recent studies suggested that dietary polyphenols may protect against MAFLD by regulating gut microbiota; however, the underlying mechanisms remain elusive. We first investigated the effects of cyanidin 3-glucoside and its phenolic metabolites on high-fat diet induced MAFLD in C57BL/6J mice, and protocatechuic acid (PCA) showed a significant positive effect. Next, regulation of PCA on lipid metabolism and gut microbiota were explored by MAFLD mouse model and fecal microbiota transplantation (FMT) experiment. Dietary PCA reduced intraperitoneal and hepatic fat deposition with lower levels of transaminases (AST &amp; ALT) and inflammatory cytokines (IL-1β, IL-2, IL-6, TNF-α &amp; MCP-1), but higher HDL-c/LDL-c ratio. Characterization of gut microbiota indicated that PCA decreased the Firmicutes/Bacteroidetes ratio mainly by reducing the relative abundance of genus Enterococcus, which was positively correlated with the levels of LDL-c, AST, ALT and most of the up-regulated hepatic lipids by lipidomics analysis. FMT experiments showed that Enterococcus faecalis caused hepatic inflammation, fat deposition and insulin resistance with decreased expression of carnitine palmitoyltransferase-1 alpha (CPT1α), which can be reversed by PCA through inhibiting Enterococcus faecalis. Transcriptomics analysis suggested that Enterococcus faecalis caused a significant decrease in the expression of fibroblast growth factor 1 (Fgf1), and PCA recovered the expression of Fgf1 with insulin-like growth factor binding protein 2 (Igfbp2), insulin receptor substrate 1 (Irs1) and insulin receptor substrate 2 (Irs2). These results demonstrated that high proportion of gut Enterococcus faecalis accelerates MAFLD with decreased expression of CPT1α and Fgf1, which can be prevented by dietary supplementation of PCA.}, }
@article {pmid37504971, year = {2023}, author = {Liu, J and Cai, J and Fan, P and Dong, X and Zhang, N and Tai, J and Cao, Y}, title = {Salidroside alleviates dextran sulfate sodium-induced colitis in mice by modulating the gut microbiota.}, journal = {Food &amp; function}, volume = {14}, number = {16}, pages = {7506-7519}, doi = {10.1039/d3fo01929b}, pmid = {37504971}, issn = {2042-650X}, abstract = {Dysbiosis causes continuous progress of inflammatory bowel disease (IBD). Herein, we aim to explore whether Salidroside (Sal), which is a major glycoside extracted from Rhodiola rosea L., could ameliorate dextran sulfate sodium (DSS)-induced colitis by modulating the microbiota. Results showed that oral treatment with 15 mg kg[-1] of Sal inhibited DSS-induced colitis in mice as evidenced by colon length, histological analysis, disease activity index (DAI) score, and the proportion and number of macrophages in the intestine. The gut microbiota of colitic mice was also partly restored by Sal. A fecal microbiota transplantation (FMT) study was designed to verify the causality. Compared with DSS-treated mice, FM from the Sal-treated donor mice significantly mitigated the symptoms of colitic mice, including reducing the DAI score, alleviating tissue damage, boosting the expression of mucin protein (mucin-2) and tight junction (TJ) proteins (occludin and zonula occludens-1 (ZO-1), and decreasing M1 macrophages in the gut. It was found that both Sal and FMT affected the structure and abundance of the gut microbiota as reflected by the decreased relative abundance of Turicibacter, Alistipes, Romboutsia and the increased relative abundance of Lactobacillus at the genus level. Moreover, the anti-inflammatory effect of Sal disappeared when the gut microbiota was depleted by antibiotics, demonstrating that Sal alleviated the intestinal inflammation in a gut microbiota-dependent manner. Thus, Sal could be a remarkable candidate as a functional food for colitis.}, }
@article {pmid37503350, year = {2023}, author = {Yang, S and Liu, G and Savelkoul, HFJ and Jansen, CA and Li, B}, title = {Mini-review: microbiota have potential to prevent PEDV infection by improved intestinal barrier.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1230937}, pmid = {37503350}, issn = {1664-3224}, mesh = {Swine ; Animals ; *Porcine epidemic diarrhea virus ; Intestines ; Intestine, Small ; *Microbiota ; *Coronavirus Infections/prevention &amp; control/veterinary ; }, abstract = {Porcine epidemic diarrhea virus (PEDV) infection poses a significant threat to the global pig industry. Current prevention and control strategies are inadequate in protecting pigs from new PEDV variants. This review aims to examine the relationship between PEDV and intestinal microbes, and investigate whether modulating intestinal microbes could affect PEDV infection. The mechanisms by which various intestinal microbes affect viral infection were initially introduced. Intestinal microbes can influence enteric viral infection through direct contact, such as binding, or by affecting interferons (IFNs) production and the intestinal barrier. Influencing the intestinal barrier by microbes can impact PEDV infection in young piglets. To narrow down the range of microbes that may influence PEDV infection, this review summarized microbes that change after infection. Short chain fatty acids (SCFAs), bacterial cell components, and toxins from microbes were identified as important mediators affecting PEDV infection. SCFAs primarily strengthen the intestinal barrier and inhibit intestinal inflammation, while bacterial cell components and toxins are more likely to damage the intestinal barrier. Therefore, this review hypothesizes that fecal transplantation, which allows the host to colonize more SCFAs-producing microbes, may prevent PEDV infection. However, these hypotheses require further proof, and the transplantation of intestinal microbes in pigs requires more exploration.}, }
@article {pmid37503065, year = {2023}, author = {Muchhala, K and Kang, M and Koseli, E and Poklis, J and Xu, Q and Dewey, W and Fettweis, J and Jimenez, N and Akbarali, H}, title = {The Role of Morphine-Induced Impairment of Intestinal Epithelial Antibacterial Activity in Dysbiosis and its Impact on the Microbiota-Gut-Brain Axis.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37503065}, issn = {2693-5015}, support = {P30 DA033934/DA/NIDA NIH HHS/United States ; R01 DA024009/DA/NIDA NIH HHS/United States ; T32 DA007027/DA/NIDA NIH HHS/United States ; }, abstract = {Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupt the intestinal epithelial layer and cause intestinal dysbiosis. Inhibiting opioid-induced dysbiosis can preclude the development of tolerance to opioid-induced antinociception, suggesting an important role of the gut-brain axis in mediating opioid effects. However, the mechanism underlying opioid-induced dysbiosis remains unclear. Host-produced antimicrobial peptides (AMPs) are critical for the integrity of the intestinal epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that chronic morphine exposure reduces expression of the antimicrobial peptide, Regenerating islet-derived 3 gamma (Reg3γ), in the ileum resulting in reduced intestinal antimicrobial activity against Gram-positive bacteria, L. reuteri. Fecal samples from morphine-treated mice had reduced levels of the phylum, Firmicutes, concomitant with reduced levels of short-chain fatty acid, butyrate. Fecal microbial transplant (FMT) from morphine-naïve mice restored the antimicrobial activity, the expression of Reg3γ, and prevented the increase in intestinal permeability and the development of antinociceptive tolerance in morphine-dependent mice. Similarly, oral gavage with sodium butyrate dose-dependently reduced the development of antinociceptive tolerance, and prevented the downregulation of Reg3γ and the reduction in antimicrobial activity. The alpha diversity of the microbiome was also restored by oral butyrate in morphine-dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which morphine disrupts the microbiota-gut-brain axis.}, }
@article {pmid37498052, year = {2023}, author = {Huang, Z and Li, Y and Park, H and Ho, M and Bhardwaj, K and Sugimura, N and Lee, HW and Meng, H and Ebert, MP and Chao, K and Burgermeister, E and Bhatt, AP and Shetty, SA and Li, K and Wen, W and Zuo, T}, title = {Unveiling and harnessing the human gut microbiome in the rising burden of non-communicable diseases during urbanization.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2237645}, pmid = {37498052}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Urbanization ; *Noncommunicable Diseases/therapy/drug therapy ; *Microbiota ; *Probiotics ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; Dysbiosis/drug therapy ; Prebiotics ; }, abstract = {The world is witnessing a global increase in the urban population, particularly in developing Asian and African countries. Concomitantly, the global burden of non-communicable diseases (NCDs) is rising, markedly associated with the changing landscape of lifestyle and environment during urbanization. Accumulating studies have revealed the role of the gut microbiome in regulating the immune and metabolic homeostasis of the host, which potentially bridges external factors to the host (patho-)physiology. In this review, we discuss the rising incidences of NCDs during urbanization and their links to the compositional and functional dysbiosis of the gut microbiome. In particular, we elucidate the effects of urbanization-associated factors (hygiene/pollution, urbanized diet, lifestyles, the use of antibiotics, and early life exposure) on the gut microbiome underlying the pathogenesis of NCDs. We also discuss the potential and feasibility of microbiome-inspired and microbiome-targeted approaches as novel avenues to counteract NCDs, including fecal microbiota transplantation, diet modulation, probiotics, postbiotics, synbiotics, celobiotics, and precision antibiotics.}, }
@article {pmid37495339, year = {2023}, author = {Barber, TM and Hanson, P and Weickert, MO}, title = {Metabolic-Associated Fatty Liver Disease and the Gut Microbiota.}, journal = {Endocrinology and metabolism clinics of North America}, volume = {52}, number = {3}, pages = {485-496}, doi = {10.1016/j.ecl.2023.01.004}, pmid = {37495339}, issn = {1558-4410}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Non-alcoholic Fatty Liver Disease ; *Liver/metabolism ; Obesity ; }, abstract = {As an important sequela of the burgeoning global obesity problem, metabolic-associated fatty liver disease (MAFLD) has gained increasing prominence recently. The gut-liver axis (GLA) provides a direct conduit to the liver for the gut microbiota and their metabolic by-products (including secondary bile acids, ethanol, and trimethylamine). These GLA-related factors, including the host inflammatory response and integrity of the gut mucosal wall, likely contribute to the pathogenesis of MAFLD. Accordingly, these GLA-related factors are targets for possible preventive and treatment strategies for MAFLD, and include probiotics, prebiotics, bile acids, short-chain fatty acids, fecal microbiota transplantation, carbon nanoparticles, and bacteriophages.}, }
@article {pmid37494556, year = {2023}, author = {Gedgaudas, R and Bajaj, JS and Skieceviciene, J and Valantiene, I and Kiudeliene, E and Bang, C and Franke, A and Schreiber, S and Kupcinskas, J}, title = {Sterile Fecal Filtrate From A Healthy Donor Improves Microbial Diversity In Patients With Hepatic Encephalopathy.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {32}, number = {3}, pages = {332-338}, doi = {10.15403/jgld-4906}, pmid = {37494556}, issn = {1842-1121}, mesh = {Humans ; *Hepatic Encephalopathy/diagnosis/etiology/therapy ; Feces/microbiology ; Fecal Microbiota Transplantation/adverse effects/methods ; Liver Cirrhosis/diagnosis/complications ; Fibrosis ; Bacteria ; }, abstract = {BACKGROUND AND AIMS: Hepatic encephalopathy (HE) remains one of the most debilitating complications of liver cirrhosis. Changes in gut microbiome composition have been linked to liver diseases and its complications including HE. Recent randomized controlled trials showed fecal microbiota transplantation to be safe and effective in HE treatment, however transferring unidentified live bacteria could cause various complications, including infections, especially in immunocompromised patients. This study aimed to evaluate the safety and efficacy of sterile fecal filtrate transfer (SFFT) for the modulation of the intestinal microbiome of patients with cirrhosis and HE.<br><br>METHODS: A custom-made air pressure filtration device was used for the sterile fecal filtrate preparation. Seven patients received SFFT from the same healthy donor. Patients were monitored at least 30 days after the procedure. Cognition tests, blood and stool sampling were performed to assess the safety and efficacy of SFFT on HE, liver function, and stool microbiome composition on follow-up days 7 and 30.<br><br>RESULTS: SFFT was well tolerated and resulted in fluctuations in the microbial composition of study participants: &#x3b1;-diversity increased in 4/7 of the patients, without robust engraftment of donors' microbial composition as assessed by &#x3b2;-diversity analysis. No significant effect on cognition tests or liver function was noted after the procedure. One death occurred three months after the procedure, however, it was not related to the SFFT.<br><br>CONCLUSIONS: Despite the effect on the gut microbiome, we did not observe robust improvement in patients' liver function or HE cognition tests after the procedure.}, }
@article {pmid37493938, year = {2023}, author = {Berry, P and Khanna, S}, title = {Recurrent Clostridioides difficile Infection: Current Clinical Management and Microbiome-Based Therapies.}, journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy}, volume = {37}, number = {6}, pages = {757-773}, pmid = {37493938}, issn = {1179-190X}, mesh = {United States ; Humans ; *Clostridioides difficile ; *Clostridium Infections/drug therapy/microbiology ; *Microbiota ; Anti-Bacterial Agents/therapeutic use ; Diarrhea/drug therapy/prevention &amp; control ; }, abstract = {Clostridioides difficile is one of the most important causes of healthcare-associated diarrhea. The high incidence and recurrence rates of C. difficile infection, as well as its associated morbidity and mortality, are great concerns. The most common complication of C. difficile infection is recurrence, with rates of 20-30% after a primary infection and 60% after three or more episodes. Medical management of recurrent C. difficile infection involves a choice of therapy that is different from the antibiotic used in the primary episode. Patients with recurrent C. difficile infection also benefit from fecal microbiota transplantation or standardized microbiome restoration therapies (approved or experimental) to restore eubiosis. In contrast to antibiotics, microbiome restoration therapies restore a normal gut flora and eliminate C. difficile colonization and infection. Fecal microbiota transplantation in recurrent C. difficile infection has demonstrated higher success rates than vancomycin, fidaxomicin, or placebo. Fecal microbiota transplantation has traditionally been considered safe, with the most common adverse reactions being abdominal discomfort, and diarrhea, and rare serious adverse events. Significant heterogeneity and a lack of standardization regarding the process of preparation, and administration of fecal microbiota transplantation remain a major pitfall. Standardized microbiome-based therapies provide a promising alternative. In the ECOSPOR III trial of SER-109, an oral formulation of bacterial spores, a significant reduction in the recurrence rate (12%) was observed compared with placebo (40%). In the phase III PUNCH CD3 trial, RBX2660 also demonstrated high efficacy rates of 70.6% versus 57.5%. Both these agents are now US Food and Drug Administration approved for recurrent C. difficile infection. Other standardized microbiome-based therapies currently in the pipeline are VE303, RBX7455, and MET-2. Antibiotic neutralization strategies, vaccines, passive monoclonal antibodies, and drug repurposing are other therapeutic strategies being explored to treat C. difficile infection.}, }
@article {pmid37491512, year = {2023}, author = {Pernigoni, N and Guo, C and Gallagher, L and Yuan, W and Colucci, M and Troiani, M and Liu, L and Maraccani, L and Guccini, I and Migliorini, D and de Bono, J and Alimonti, A}, title = {The potential role of the microbiota in prostate cancer pathogenesis and treatment.}, journal = {Nature reviews. Urology}, volume = {20}, number = {12}, pages = {706-718}, pmid = {37491512}, issn = {1759-4820}, support = {MR/W018217/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Male ; Humans ; *Prostatic Neoplasms/therapy/genetics ; *Probiotics/therapeutic use ; Prostate/pathology ; *Gastrointestinal Microbiome ; Carcinogenesis ; }, abstract = {The human body hosts a complex and dynamic population of trillions of microorganisms - the microbiota - which influences the body in homeostasis and disease, including cancer. Several epidemiological studies have associated specific urinary and gut microbial species with increased risk of prostate cancer; however, causal mechanistic data remain elusive. Studies have associated bacterial generation of genotoxins with the occurrence of TMPRSS2-ERG gene fusions, a common, early oncogenic event during prostate carcinogenesis. A subsequent study demonstrated the role of the gut microbiota in prostate cancer endocrine resistance, which occurs, at least partially, through the generation of androgenic steroids fuelling oncogenic signalling via the androgen receptor. These studies present mechanistic evidence of how the host microbiota might be implicated in prostate carcinogenesis and tumour progression. Importantly, these findings also reveal potential avenues for the detection and treatment of prostate cancer through the profiling and modulation of the host microbiota. The latter could involve approaches such as the use of faecal microbiota transplantation, prebiotics, probiotics, postbiotics or antibiotics, which can be used independently or combined with existing treatments to reverse therapeutic resistance and improve clinical outcomes in patients with prostate cancer.}, }
@article {pmid37491256, year = {2023}, author = {He, S and Li, J and Yao, Z and Gao, Z and Jiang, Y and Chen, X and Peng, L}, title = {Insulin alleviates murine colitis through microbiome alterations and bile acid metabolism.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {498}, pmid = {37491256}, issn = {1479-5876}, mesh = {Mice ; Humans ; Animals ; Insulin ; RNA, Ribosomal, 16S/genetics ; *Colitis/drug therapy ; *Inflammatory Bowel Diseases/drug therapy ; Inflammation ; *Gastrointestinal Microbiome/genetics ; Bile Acids and Salts ; Receptors, G-Protein-Coupled ; Anti-Inflammatory Agents ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Insulin has been reported to exhibit anti-inflammatory activities in the context of bowel inflammation. However, the role of the interaction between insulin and the microbiota in gut health is unclear. Our goal was to investigate the mechanism of action of insulin in bowel inflammation and the relationship between insulin and the gut microbiota.<br><br>METHODS: We used acute and chronic murine models of inflammatory bowel disease (IBD) to evaluate whether insulin influences the progression of colitis. Colonic tissues, the host metabolome and the gut microbiome were analyzed to investigate the relationship among insulin treatment, the microbiome, and disease. Experiments involving antibiotic (Abx) treatment and fecal microbiota transplantation (FMT) confirmed the association among the gut microbiota, insulin and IBD. In a series of experiments, we further defined the mechanisms underlying the anti-inflammatory effects of insulin.<br><br>RESULTS: We found that low-dose insulin treatment alleviated intestinal inflammation but did not cause death. These effects were dependent on the gut microbiota, as confirmed by experiments involving Abx treatment and FMT. Using untargeted metabolomic profiling and 16S rRNA sequencing, we discovered that the level of the secondary bile acid lithocholic acid (LCA) was notably increased and the LCA levels were significantly associated with the abundance of Blautia, Enterorhadus and Rumi-NK4A214_group. Furthermore, LCA exerted anti-inflammatory effects by activating a G-protein-coupled bile acid receptor (TGR5), which inhibited the polarization of classically activated (M1) macrophages.<br><br>CONCLUSION: Together, these data suggest that insulin alters the gut microbiota and affects LCA production, ultimately delaying the progression of IBD.}, }
@article {pmid37486121, year = {2023}, author = {Zhang, K and Yang, J and Chen, L and He, J and Qu, D and Zhang, Z and Liu, Y and Li, X and Liu, J and Li, J and Xie, X and Wang, Q}, title = {Gut Microbiota Participates in Polystyrene Microplastics-Induced Hepatic Injuries by Modulating the Gut-Liver Axis.}, journal = {ACS nano}, volume = {17}, number = {15}, pages = {15125-15145}, doi = {10.1021/acsnano.3c04449}, pmid = {37486121}, issn = {1936-086X}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Microplastics ; Plastics ; Polystyrenes/pharmacology ; Inflammation ; }, abstract = {Dietary pollution by polystyrene microplastics (MPs) can cause hepatic injuries and microbial dysbiosis. Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, exerts beneficial effects on the liver by modulating the gut microbiota. However, the role of microbiota in MPs-induced hepatic injuries and the protective effect of EGCG have not been clarified. Here, 5 μm MPs were orally administered to mice to induce hepatic injuries. Subsequently, antibiotic cocktail (ABX) and fecal microbial transplant (FMT) experiments were performed to investigate the underlying microbial mechanisms. Additionally, EGCG was orally administered to mice to explore its protection against MPs-induced hepatic injuries. Our results showed that MPs activated systemic and hepatic inflammation, promoted fibrosis, and altered the liver metabolome; meanwhile, MPs damaged the gut homeostasis by disturbing the gut microbiome, promoting colonic inflammation, and impairing the intestinal barrier. Notably, MPs reduced the abundance of the probiotics Akkermansia, Mucispirillum, and Faecalibaculum while increasing the pathogenic Tuzzerella. Interestingly, the elimination of gut microbiota mitigated MPs-induced colonic inflammation and intestinal barrier impairment. Moreover, ABX ameliorated MPs-induced systemic and hepatic inflammation but not fibrosis. Correspondingly, microbiota from MPs-administered mice induced colonic, systemic, and hepatic inflammation, while their profibrosis effect on the liver was not observed. Finally, EGCG elevated the abundance of probiotics and effectively repressed MPs-induced colonic inflammation. MPs-induced systemic and hepatic inflammation, fibrosis, and remodeling of the liver metabolome were also attenuated by EGCG. These findings illustrated that gut microbiota contributed to MPs-induced colonic and hepatic injuries, while EGCG could serve as a potential prevention strategy for these adverse consequences.}, }
@article {pmid37484415, year = {2023}, author = {Churchward, MA and Michaud, ER and Mullish, BH and Miguens Blanco, J and Garcia Perez, I and Marchesi, JR and Xu, H and Kao, D and Todd, KG}, title = {Short-chain fatty and carboxylic acid changes associated with fecal microbiota transplant communally influence microglial inflammation.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e16908}, pmid = {37484415}, issn = {2405-8440}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {The intestinal microbiota has been proposed to influence human mental health and cognition through the gut-brain axis. Individuals experiencing recurrent Clostridioides difficile infection (rCDI) frequently report depressive symptoms, which are improved after fecal microbiota transplantation (FMT); however, mechanisms underlying this association are poorly understood. Short-chain fatty acids and carboxylic acids (SCCA) produced by the intestinal microbiota cross the blood brain barrier and have been proposed to contribute to gut-brain communication. We hypothesized that changes in serum SCCA measured before and after successful FMT for rCDI influences the inflammatory response of microglia, the resident immune cells of the central nervous system. Serum SCCA were quantified using gas chromatography-mass spectroscopy from 38 patients who participated in a randomized trial comparing oral capsule-vs colonoscopy-delivered FMT for rCDI, and quality of life was assessed by SF-36 at baseline, 4, and 12 weeks after FMT treatment. Successful FMT was associated with improvements in mental and physical health, as well as significant changes in a number of circulating SCCA, including increased butyrate, 2-methylbutyrate, valerate, and isovalerate, and decreased 2-hydroxybutyrate. Primary cultured microglia were treated with SCCA and the response to a pro-inflammatory stimulus was measured. Treatment with a combination of SCCA based on the post-FMT serum profile, but not single SCCA species, resulted in significantly reduced inflammatory response including reduced cytokine release, reduced nitric oxide release, and accumulation of intracellular lipid droplets. This suggests that both levels and diversity of SCCA may be an important contributor to gut-brain communication.}, }
@article {pmid37483406, year = {2023}, author = {Shi, H and Chen, M and Zheng, C and Yinglin, B and Zhu, B}, title = {Fecal Microbiota Transplantation Alleviated Paclitaxel-Induced Peripheral Neuropathy by Interfering with Astrocytes and TLR4/p38MAPK Pathway in Rats.}, journal = {Journal of pain research}, volume = {16}, number = {}, pages = {2419-2432}, pmid = {37483406}, issn = {1178-7090}, abstract = {PURPOSE: Paclitaxel-induced peripheral neuropathy (PIPN) constitutes a refractory and progressive adverse consequence of paclitaxel treatment, causing pain and sensory anomalies in cancer survivors. Although the gut-brain axis is involved in multiple disorders including cancer, its impact on peripheral pain conditions remains elusive. Thus, we assessed the importance of gut microbiota and related mechanisms in PIPN.<br><br>METHODS: By implementing fecal microbiota transplantation (FMT) in a rat PIPN model (ie, rats treated with paclitaxel; hereafter as PIPN rats), we explored the effect of gut microbiota on PIPN rats using multiple methods, including different behavioral tests, 16S ribosomal DNA (rDNA) sequencing, and biochemical techniques.<br><br>RESULTS: Sequencing of 16S rDNA revealed that the abundance of genera Bacteroides and UCG-005 increased, while that of genera Turicibacter, Clostridium sensu stricto 1 and Corynebacterium decreased in the PIPN rats. However, when treated with FMT using fecal from normal rats, the mechanical allodynia and thermal hyperalgesia in PIPN rats were significantly alleviated. In addition, FMT treatment reduced the expression of toll-like receptor 4 (TLR4), phospho-p38 mitogen-activated protein kinase (p-p38MAPK), and the astrocytic marker glial fibrillary acidic protein in the colon and spinal dorsal horn. TAK242 (a TLR4 inhibitor) significantly alleviated the behavioral hypersensitivity of PIPN rats and inhibited the TLR4/p38MAPK pathway in astrocytes in these rats.<br><br>CONCLUSION: The gut microbiota played a critical role in PIPN. Future therapies treating PIPN should consider microbe-based treatment as an option.}, }
@article {pmid37482926, year = {2023}, author = {Baunwall, SMD and Hansen, MM and Andreasen, SE and Eriksen, MK and Rågård, N and Kelsen, J and Grosen, AK and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Donor, patient age and exposure to antibiotics are associated with the outcome of faecal microbiota transplantation for recurrent Clostridioides difficile infection: A prospective cohort study.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {58}, number = {5}, pages = {503-515}, doi = {10.1111/apt.17642}, pmid = {37482926}, issn = {1365-2036}, mesh = {Humans ; Aged ; *Fecal Microbiota Transplantation/adverse effects/methods ; Anti-Bacterial Agents/therapeutic use ; Prospective Studies ; Cohort Studies ; *Clostridium Infections/therapy ; Treatment Outcome ; Recurrence ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI), but its effect varies inexplicably.<br><br>AIMS: To optimise the effectiveness of FMT for rCDI and validate determinants for effect METHODS: We conducted a cohort study, including all patients treated with FMT for rCDI between October 2018 and June 2020. Statistical process control was used to evaluate the impact of prospective quality improvement on the effect of single FMT treatments per 10-11 patients. Targeting an 80% effect, optimisations included changes to processing procedures, preparation and clinical application of FMT. The primary outcome was the resolution of Clostridioides difficile-associated diarrhoea at week 8. If CDI recurred, FMT was repeated. All patients were followed for 8&#x2009;weeks after their latest FMT.<br><br>RESULTS: 183 patients with rCDI received 290 FMT treatments. A single FMT achieved resolution at week 8 in 127 (69%, 95% CI: 62%-76%), while repeated FMT cumulatively achieved resolution in 167/183 (91%, 95% CI: 86%-95%). The single FMT effect varied between 36% and 100% over time. In a mixed-effect model, patient age above 65&#x2009;years, non-rCDI antibiotics at week 1 post-FMT, and donor were associated with effect. Neither increasing the dosages of faecal microbes nor standardising the processing improved outcomes.<br><br>CONCLUSION: FMT has a high cumulative effectiveness in patients with rCDI following multiple administrations, but the single FMT effect is variable and may be optimised using statistical process control. Optimising FMT by considering patient age, post-FMT antibiotics, donor and multiple administrations may improve the treatment outcomes.<br><br>CLINICALTRIALS: gov (Study identifier: NCT03712722).}, }
@article {pmid37482657, year = {2023}, author = {Wang, Z and Dan, W and Zhang, N and Fang, J and Yang, Y}, title = {Colorectal cancer and gut microbiota studies in China.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2236364}, pmid = {37482657}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Colorectal Neoplasms/diagnosis ; Carcinogenesis ; China ; Biomarkers ; }, abstract = {Colorectal cancer (CRC) is the third most common malignant tumor worldwide. The incidence and mortality rates of CRC have been increasing in China, possibly due to economic development, lifestyle, and dietary changes. Evidence suggests that gut microbiota plays an essential role in the tumorigenesis of CRC. Gut dysbiosis, specific pathogenic microbes, metabolites, virulence factors, and microbial carcinogenic mechanisms contribute to the initiation and progression of CRC. Gut microbiota biomarkers have potential translational applications in CRC screening and early diagnosis. Gut microbiota-related interventions could improve anti-tumor therapy's efficacy and severe intestinal toxic effects. Chinese researchers have made many achievements in the relationship between gut microbiota and CRC, although some challenges remain. This review summarizes the current evidence from China on the role of gut microbiota in CRC, mainly including the gut microbiota characteristics, especially Fusobacterium nucleatum and Parvimonas micra, which have been identified to be enriched in CRC patients; microbial pathogens such as F. nucleatum and enterotoxigenic Bacteroides fragilis, and P. micra, which Chinese scientists have extensively studied; diagnostic biomarkers especially F. nucleatum; therapeutic effects, including microecological agents represented by certain Lactobacillus strains, fecal microbiota transplantation, and traditional Chinese medicines such as Berberine and Curcumin. More efforts should be focused on exploring the underlying mechanisms of microbial pathogenesis of CRC and providing novel gut microbiota-related therapeutic and preventive strategies.}, }
@article {pmid37478946, year = {2023}, author = {Zhang, L and Kang, H and Zhang, W and Wang, J and Liu, Z and Jing, J and Han, L and Gao, A}, title = {Probiotics ameliorate benzene-induced systemic inflammation and hematopoietic toxicity by inhibiting Bacteroidaceae-mediated ferroptosis.}, journal = {The Science of the total environment}, volume = {899}, number = {}, pages = {165678}, doi = {10.1016/j.scitotenv.2023.165678}, pmid = {37478946}, issn = {1879-1026}, mesh = {Humans ; Animals ; Mice ; *Ferroptosis ; Benzene/toxicity ; Bacteroidaceae ; Inflammation/chemically induced ; *Probiotics/pharmacology ; *Hematopoietic Stem Cell Transplantation ; }, abstract = {The intestinal microbiota is associated with the development of benzene-induced hematopoietic toxicity. Modulation of intestinal homeostasis by probiotic supplementation has been considered an effective strategy to prevent adverse health effects. However, the role and mechanism of probiotics in benzene-induced hematopoietic toxicity are unclear. After 45 days of exposure, benzene caused bone marrow hematopoietic toxicity in mice. Furthermore, we found that benzene altered the intestinal barrier in mice, leading to an increase in the abundance of Bacteroidaceae and the activation of systemic inflammation. Interestingly, Fe[2+] accumulation, lipid peroxidation, and differential expression of ferroptosis proteins were observed in the intestinal tissues of benzene-exposed mice. After fecal microbiota transplantation, stool microbes from benzene-exposed mice led to the development of intestinal ferroptosis in recipient mice. In particular, oral probiotics significantly reversed elevated Bacteroidaceae and intestinal ferroptosis, ultimately improving benzene-induced hematopoietic damage. We further used the benzene metabolite 1,4-BQ to treat human normal colonic epithelial cells (NCM460) and intervened with the ferroptosis inhibitor liproxstatin-1 (Lip-1) to validate the relationship between intestinal ferroptosis and inflammation. The results showed that 1,4-BQ treatment resulted in increased intracellular ROS levels and abnormal expression of ferroptosis proteins and the inflammatory factors IL-5 and IL-13. However, the use of Lip-1 significantly inhibited oxidative stress, ferroptosis, and inflammation in NCM460 cells. This result suggested that ferroptosis might be involved in benzene-induced hematopoietic toxicity by mediating Th2-type systemic inflammation. Overall, these findings revealed a role for Bacteroidaceae-intestinal ferroptosis-inflammation in benzene-induced hematopoietic toxicity and highlighted that probiotics could be a promising strategy to prevent adverse hematologic outcomes.}, }
@article {pmid37477511, year = {2023}, author = {Granger, MF and Kelly, M and Fortier, LC and Fournier, E and Côté-Gravel, J and Malouin, F and Valiquette, L and Lévesque, S}, title = {Chronic Diarrhea Caused by a Klebsiella oxytoca Toxin Producer Strain Following Antibiotic-Associated Hemorrhagic Colitis: Successful Treatment by Fecal Microbiota Transplant.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {12}, pages = {1700-1703}, doi = {10.1093/cid/ciad436}, pmid = {37477511}, issn = {1537-6591}, support = {2015-05916//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2020-05776//Natural Sciences and Engineering Council of Canada/ ; }, mesh = {Humans ; Klebsiella oxytoca ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation/adverse effects ; *Klebsiella Infections/microbiology ; *Enterocolitis, Pseudomembranous/etiology ; Diarrhea/drug therapy ; *Colitis/complications/drug therapy ; }, abstract = {Klebsiella oxytoca is a gram-negative bacterium found in fecal microbiota and known to cause several infections in humans, including antibiotic-associated hemorrhagic colitis. We present here a case of colitis caused by K. oxytoca toxin-producing strains that evolved in chronic diarrhea successfully treated by fecal microbiota transplant.}, }
@article {pmid37475750, year = {2023}, author = {Videvall, E and Bensch, HM and Engelbrecht, A and Cloete, S and Cornwallis, CK}, title = {Coprophagy rapidly matures juvenile gut microbiota in a precocial bird.}, journal = {Evolution letters}, volume = {7}, number = {4}, pages = {240-251}, pmid = {37475750}, issn = {2056-3744}, abstract = {Coprophagy is a behavior where animals consume feces, and has been observed across a wide range of species, including birds and mammals. The phenomenon is particularly prevalent in juveniles, but the reasons for this remain unclear. One hypothesis is that coprophagy enables offspring to acquire beneficial gut microbes that aid development. However, despite the potential importance of this behavior, studies investigating the effects in juveniles are rare. Here we experimentally test this idea by examining how ingestion of adult feces by ostrich chicks affects their gut microbiota development, growth, feeding behavior, pathogen abundance, and mortality. We conducted extensive longitudinal experiments for 8 weeks, repeated over 2 years. It involved 240 chicks, of which 128 were provided daily access to fresh fecal material from adults and 112 were simultaneously given a control treatment. Repeated measures, behavioral observations, and DNA metabarcoding of the microbial gut community, both prior to and over the course of the experiment, allowed us to evaluate multiple aspects of the behavior. The results show that coprophagy causes (a) marked shifts to the juvenile gut microbiota, including a major increase in diversity and rapid maturation of the microbial composition, (b) higher growth rates (fecal-supplemented chicks became 9.4% heavier at 8 weeks old), (c) changes to overall feeding behavior but no differences in feed intake, (d) lower abundance of a common gut pathogen (Clostridium colinum), and (e) lower mortality associated with gut disease. Together, our results suggest that the behavior of coprophagy in juveniles is highly beneficial and may have evolved to accelerate the development of gut microbiota.}, }
@article {pmid37475479, year = {2023}, author = {Lawenius, L and Cowardin, C and Grahnemo, L and Scheffler, JM and Horkeby, K and Engdahl, C and Wu, J and Vandenput, L and Koskela, A and Tuukkanen, J and Coward, E and Hveem, K and Langhammer, A and Abrahamsson, S and Gordon, JI and Sjögren, K and Ohlsson, C}, title = {Transplantation of gut microbiota from old mice into young healthy mice reduces lean mass but not bone mass.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2236755}, pmid = {37475479}, issn = {1949-0984}, support = {T32 AI007172/AI/NIAID NIH HHS/United States ; }, mesh = {Young Adult ; Humans ; Mice ; Animals ; Aged ; Infant ; *Gastrointestinal Microbiome ; *Microbiota ; Fecal Microbiota Transplantation ; Aging ; Cecum ; }, abstract = {Aging is associated with low bone and lean mass as well as alterations in the gut microbiota (GM). In this study, we determined whether the reduced bone mass and relative lean mass observed in old mice could be transferred to healthy young mice by GM transplantation (GMT). GM from old (21-month-old) and young adult (5-month-old) donors was used to colonize germ-free (GF) mice in three separate studies involving still growing 5- or 11-week-old recipients and 17-week-old recipients with minimal bone growth. The GM of the recipient mice was similar to that of the donors, demonstrating successful GMT. GM from old mice did not have statistically significant effects on bone mass or bone strength, but significantly reduced the lean mass percentage of still growing recipient mice when compared with recipients of GM from young adult mice. The levels of propionate in the cecum of mice receiving old donor GM were significantly lower than those in mice receiving young adult donor GM. Bacteroides ovatus was enriched in the microbiota of recipient mice harboring GM from young adult donors. The presence of B. ovatus was not only significantly associated with high lean mass percentage in mice, but also with lean mass adjusted for fat mass in the large human HUNT cohort. In conclusion, GM from old mice reduces lean mass percentage but not bone mass in young, healthy, still growing recipient mice. Future studies are warranted to determine whether GM from young mice improves the musculoskeletal phenotype of frail elderly recipient mice.}, }
@article {pmid37475473, year = {2023}, author = {Borin, JM and Liu, R and Wang, Y and Wu, TC and Chopyk, J and Huang, L and Kuo, P and Ghose, C and Meyer, JR and Tu, XM and Schnabl, B and Pride, DT}, title = {Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2236750}, pmid = {37475473}, issn = {1949-0984}, support = {P30 DK120515/DK/NIDDK NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; }, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation ; Virome ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Obesity/microbiology ; *Microbiota ; Diet, High-Fat/adverse effects ; Bacteria/genetics ; *Viruses ; Phenotype ; Mice, Inbred C57BL ; }, abstract = {The gastrointestinal microbiome plays a significant role in modulating numerous host processes, including metabolism. Prior studies show that when mice receive fecal transplants from obese donors on high-fat diets (HFD) (even when recipient mice are fed normal diets after transplantation), they develop obese phenotypes, demonstrating the prominent role that gut microbiota play in determining lean and obese phenotypes. While much of the credit has been given to gut bacteria, the impact of gut viruses on these phenotypes is understudied. To address this shortcoming, we gavaged mice with viromes isolated from donors fed HFD or normal chow over a 4-week study. By characterizing the gut bacterial biota via 16S rRNA amplicon sequencing and measuring mouse weights over time, we demonstrate that transplanted viruses affect the gut bacterial community, as well as weight gain/loss. Notably, mice fed chow but gavaged with HFD-derived viromes gained more weight than their counterparts receiving chow-derived viromes. The converse was also true: mice fed HFD but gavaged with chow-derived viromes gained less weight than their counterparts receiving HFD-derived viromes. Results were replicated in two independent experiments and phenotypic changes were accompanied by significant and identifiable differences in the fecal bacterial biota. Due to methodological limitations, we were unable to identify the specific bacterial strains responsible for respective phenotypic changes. This study confirms that virome-mediated perturbations can alter the fecal microbiome in vivo and indicates that such perturbations are sufficient to drive lean and obese phenotypes in mice.}, }
@article {pmid37474764, year = {2023}, author = {Chuang, C and Lee, KC and Wang, YP and Lee, PC and Chang, TE and Huang, YH and Lin, YT and Hou, MC}, title = {High carriage rate of extended-spectrum β-lactamase Enterobacterales and diarrheagenic Escherichia coli in healthy donor screening for fecal microbiota transplantation.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {42}, number = {9}, pages = {1103-1113}, pmid = {37474764}, issn = {1435-4373}, support = {V107E-007-1 (108)//Taipei Veterans General Hospital/ ; V108E-007-1 (108)//Taipei Veterans General Hospital/ ; V108E-007-1 (109)//Taipei Veterans General Hospital/ ; V110E-002-1//Taipei Veterans General Hospital/ ; }, mesh = {Humans ; *Escherichia coli ; Fecal Microbiota Transplantation ; Donor Selection ; beta-Lactamases/genetics ; *Escherichia coli Infections/diagnosis/epidemiology/microbiology ; Klebsiella pneumoniae ; Feces/microbiology ; Anti-Bacterial Agents ; Microbial Sensitivity Tests ; }, abstract = {The safety of fecal microbiota transplantation (FMT) has been highlighted by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli bacteremia transmitted from donors and acquisition of diarrheagenic E. coli (Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC)) via FMT. The use of donor screening criteria to lower the risk of pathogen transmission via FMT is essential. This study aimed to demonstrate the outcomes of our strict donor screening program. This study was conducted at our FMT center between January 2019 and June 2022. Our donor screening program included an initial questionnaire and subsequent blood and stool testing. We further used selective culture for third-generation cephalosporin-resistant (3GCR) Enterobacterales and multiplex PCR to detect diarrheagenic E. coli in stools. The resistance mechanisms and sequence type of 3GCR Enterobacterales were determined. A total of 742 individuals were assessed, and 583 participants (78.6%) were excluded after questionnaire. Of the remaining 159 participants undergoing stool and blood tests, 37 participants were finally qualified (5.0%, 37/742). A high fecal carriage rate of ESBL-producing Enterobacterales (35.2%, 56/159), including E. coli (n=53) and Klebsiella pneumoniae (n=5), and diarrheagenic E. coli (31.4%, 50/159), including EPEC (n=41), enteroaggregative E. coli (n=11), enterotoxigenic E. coli (n=4), and STEC (n=1), was noted. CTX-M-79 and CTX-M-15 were dominant in E. coli and K. pneumoniae, respectively. The sequence types of the ESBL-producing strains were diverse. The screening for 3GCR Enterobacterales and diarrheagenic E. coli in stool is necessary. Our findings also support the effectiveness of multiplex PCR panels in FMT donor screening programs.}, }
@article {pmid37474544, year = {2023}, author = {Castellini, G and Cassioli, E and Vitali, F and Rossi, E and Dani, C and Melani, G and Flaccomio, D and D'Andria, M and Mejia Monroy, M and Galli, A and Cavalieri, D and Ricca, V and Bartolucci, GL and De Filippo, C}, title = {Gut microbiota metabolites mediate the interplay between childhood maltreatment and psychopathology in patients with eating disorders.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11753}, pmid = {37474544}, issn = {2045-2322}, mesh = {Humans ; Child ; Adolescent ; Young Adult ; *Gastrointestinal Microbiome ; *Feeding and Eating Disorders ; *Anorexia Nervosa/psychology ; Butyrates ; *Child Abuse ; }, abstract = {Eating disorders (EDs) are syndromes with a multifactorial etiopathogenesis, involving childhood traumatic experiences, as well as biological factors. Human microbiome has been hypothesised to play a fundamental role, impacting on emotion regulation, as well as with eating behaviours through its metabolites such as short chain fatty acids (SCFAs). The present study investigated the interactions between psychopathology of EDs, the gut microbiome and SCFAs resulting from bacterial community metabolic activities in a population of 47 patients with Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder and in healthy controls (HCs). Bacterial gut microbiota composition differences were found between subjects with EDs and HCs, especially in association with different pathological behaviours (binge-purge vs restricting). A mediation model of early trauma and ED-specific psychopathology linked reduction of microbial diversity to a typical microbiota-derived metabolite such as butyric acid. A possible interpretation for this model might be that childhood trauma represents a risk factor for gut dysbiosis and for a stable modification of mechanisms responsible for SCFAs production, and that this dysfunctional community is inherited in the passage from childhood to adulthood. These findings might open the way to novel interventions of butyric acid-like compounds as well as faecal transplant.}, }
@article {pmid37474412, year = {2024}, author = {Ribaldone, DG and Parisio, L and Variola, A and Bossa, F and Castiglione, F and Marzo, M and Piazza, N and Aratari, A and Savarino, EV and Bodini, G and Mastronardi, M and Micheli, F and Mazzuoli, S and Ascolani, M and Viganò, C and Cappello, M and Bezzio, C and Ciccocioppo, R and Scardino, G and Sarli, E and Pugliese, D and Scaldaferri, F and Napolitano, D and Todeschini, A and Geccherle, A and Colaci, N and Guerra, M and Annese, M and Testa, A and Caiazzo, A and Conforti, FS and Festa, S and Lorenzon, G and Marra, A and Magiotta, A and Baccini, F and Amato, A and Poshnjari, A and Vernero, M and Caprioli, F and Caviglia, GP and , }, title = {Switching from VEDOlizumab intravenous to subcutaneous formulation in ulcerative colitis patients in clinical remission: The SVEDO Study, an IG-IBD study.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {56}, number = {1}, pages = {77-82}, doi = {10.1016/j.dld.2023.07.011}, pmid = {37474412}, issn = {1878-3562}, mesh = {Humans ; Administration, Intravenous ; *Colitis, Ulcerative/drug therapy ; Gastrointestinal Agents ; *Inflammatory Bowel Diseases/drug therapy ; Prospective Studies ; Steroids/therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: The administration of biological drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations.<br><br>AIMS: To evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis (UC) patients in corticosteroid-free clinical remission.<br><br>METHODS: An observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD (IG-IBD). UC patients in clinical remission (pMAYO < 2) not receiving steroids for > 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO &#x2265; 2) or needing oral steroids or stopping subcutaneous vedolizumab during the 6 months of follow-up after the switch.<br><br>RESULTS: Overall, 168 patients were included. The switch was a success in 134 patients (79.8%). Vedolizumab retention rate was 88.7% at month six. C-reactive protein and faecal calprotectin values did not change after the switch (p&#xa0;=&#xa0;0.07 and p&#xa0;=&#xa0;0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation recapturing clinical remission in 80%. Side effects were observed in 22 patients (13.1%).<br><br>CONCLUSION: Effectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting.}, }
@article {pmid37473910, year = {2023}, author = {Zhao, Q and Chen, J and Wu, M and Yin, X and Jiang, Q and Gao, H and Zheng, H}, title = {Microbiota from healthy mice alleviates cognitive decline via reshaping the gut-brain metabolic axis in diabetic mice.}, journal = {Chemico-biological interactions}, volume = {382}, number = {}, pages = {110638}, doi = {10.1016/j.cbi.2023.110638}, pmid = {37473910}, issn = {1872-7786}, mesh = {Mice ; Animals ; Brain-Gut Axis ; *Diabetes Mellitus, Type 1 ; *Diabetes Mellitus, Experimental/therapy ; *Microbiota ; Brain ; *Cognitive Dysfunction/therapy ; }, abstract = {Diabetic cognitive decline has been associated with the gut microbial disorders, but its potential gut-brain axis mechanisms remain unclear. Herein we transplanted the gut microbiota from healthy mice into type 1 diabetic (T1D) mice and then investigated the effect of fecal microbiota transplantation (FMT) on cognitive function and the gut-brain metabolic axis. The results demonstrate that FMT from healthy mice effectively improved the learning and memory abilities in T1D mice, and significantly reduced neuroinflammation and neuron injury in the cortex and hippocampus. Moreover, FMT partly reversed the gut microbiota and gut-brain metabolic disorders, particularly glutamate metabolism. In vitro study, we found that glutamate notably decreased microglia activation and the expression levels of proinflammatory factor. Hence, our study suggests that glutamate serves as a key signal metabolite connecting the gut to brain and affects cognitive functions.}, }
@article {pmid37471410, year = {2023}, author = {Qiu, B and Liang, J and Li, C}, title = {Effects of fecal microbiota transplantation in metabolic syndrome: A meta-analysis of randomized controlled trials.}, journal = {PloS one}, volume = {18}, number = {7}, pages = {e0288718}, pmid = {37471410}, issn = {1932-6203}, mesh = {Humans ; Cholesterol, HDL ; Diabetes Mellitus, Type 2/therapy ; Fecal Microbiota Transplantation ; Glycated Hemoglobin ; *Metabolic Syndrome/therapy ; *Obesity/therapy ; Randomized Controlled Trials as Topic ; }, abstract = {OBJECTIVE: The prevalence of obesity and type 2 diabetes is rapidly increasing worldwide, posing serious threats to human health. This study aimed to evaluate the role of FMT in the treatment of obesity and/or metabolic syndrome and its impact on clinically important parameters.<br><br>METHODS: We searched Medline, Embase, and Cochrane Library databases up to April 31, 2022 and further assessed articles that met the eligibility criteria. Mean differences and 95% confidence intervals were used to analyze continuous data. The I2 statistic was used to measure study heterogeneity. Univariate meta-regression or subgroup analyses were performed to explore the covariates that might contribute to heterogeneity. Potential publication bias was assessed using the Egger's test. We used the GRADEpro guideline development tool to assess the quality of the evidence.<br><br>RESULTS: Nine studies, comprising 303 participants, were included in the meta-analysis. In the short-term outcomes (<6 weeks after FMT), compared with the placebo group, patients in the FMT group had lower FBG (MD = -0.12 mmol/L, 95% Cl: -0.23, -0.01), HbA1c (MD = -0.37 mmol/mol, 95%Cl: -0.73, -0.01), and insulin levels (MD = -24.77 mmol/L, 95% Cl: -37.60, -11.94), and higher HDL cholesterol levels (MD = 0.07 mmol/L, 95% Cl: 0.02, 0.11).<br><br>CONCLUSIONS: FMT, as an adjunctive therapy, does not produce any serious adverse effects and may be useful in the treatment of metabolic syndrome, especially in improving HbA1c, insulin sensitivity, and HDL cholesterol. However, there was no significant difference between the FMT group and the placebo group in terms of weight reduction.}, }
@article {pmid37470727, year = {2024}, author = {Wang, W and Cui, B and Nie, Y and Sun, L and Zhang, F}, title = {Radiation injury and gut microbiota-based treatment.}, journal = {Protein &amp; cell}, volume = {15}, number = {2}, pages = {83-97}, pmid = {37470727}, issn = {1674-8018}, support = {2021YFA0717004//National Key Research and Development Program of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Microbiota ; Fecal Microbiota Transplantation ; *Radiation Injuries/therapy ; }, abstract = {The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury (RI). RI is a common disease involving multiple human body parts and organs, yet effective treatments are currently limited. Accumulating evidence suggests gut microbiota are closely associated with the development and prevention of various RI. This article summarizes 10 common types of RI and their possible mechanisms. It also highlights the changes and potential microbiota-based treatments for RI, including probiotics, metabolites, and microbiota transplantation. Additionally, a 5P-Framework is proposed to provide a comprehensive strategy for managing RI.}, }
@article {pmid37469740, year = {2023}, author = {Singh, SV and Ganguly, R and Jaiswal, K and Yadav, AK and Kumar, R and Pandey, AK}, title = {Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review.}, journal = {World journal of clinical cases}, volume = {11}, number = {19}, pages = {4458-4476}, pmid = {37469740}, issn = {2307-8960}, abstract = {Irritable bowel syndrome (IBS) is a chronic functional disorder which alters gastrointestinal (GI) functions, thus leading to compromised health status. Pathophysiology of IBS is not fully understood, whereas abnormal gut brain axis (GBA) has been identified as a major etiological factor. Recent studies are suggestive for visceral hyper-sensitivity, altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients. Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors, such as microbiota population and diversity, microbial metabolites, dietary uptake, and psychological abnormalities. Strategic efforts focused to study these interactions including probiotics, antibiotics and fecal transplantations in normal and germ-free animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology. Additionally, neurotransmitters act as communication tools between enteric microbiota and brain functions, where serotonin (5-hydroxytryptamine) plays a key role in pathophysiology of IBS. It regulates GI motility, pain sense and inflammatory responses particular to mucosal and brain activity. In the absence of a better understanding of various interconnected crosstalks in GBA, more scientific efforts are required in the search of novel and targeted therapies for the management of IBS. In this review, we have summarized the gut microbial composition, interconnected signalling pathways and their regulators, available therapeutics, and the gaps needed to fill for a better management of IBS.}, }
@article {pmid37469721, year = {2023}, author = {da Ponte Neto, AM and Clemente, ACO and Rosa, PW and Ribeiro, IB and Funari, MP and Nunes, GC and Moreira, L and Sparvoli, LG and Cortez, R and Taddei, CR and Mancini, MC and de Moura, EGH}, title = {Fecal microbiota transplantation in patients with metabolic syndrome and obesity: A randomized controlled trial.}, journal = {World journal of clinical cases}, volume = {11}, number = {19}, pages = {4612-4624}, pmid = {37469721}, issn = {2307-8960}, abstract = {BACKGROUND: Metabolic syndrome is a multifactorial disease, and the gut microbiota may play a role in its pathogenesis. Obesity, especially abdominal obesity, is associated with insulin resistance, often increasing the risk of type two diabetes mellitus, vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease.<br><br>AIM: To evaluate the outcomes of fecal microbiota transplantation (FMT) in patients with metabolic syndrome.<br><br>METHODS: This was a randomized, single-blind placebo-controlled trial comparing FMT and a sham procedure in patients with metabolic syndrome. We selected 32 female patients, who were divided into eight groups of four patients each. All of the patients were submitted to upper gastrointestinal endoscopy. In each group, two patients were randomly allocated to undergo FMT, and the other two patients received saline infusion. The patients were followed for one year after the procedures, during which time anthropometric, bioimpedance, and biochemical data were collected. The patients also had periodic consultations with a nutritionist and an endocrinologist. The primary end point was a change in the gut microbiota.<br><br>RESULTS: There was evidence of a postprocedural change in microbiota composition in the patients who underwent FMT in relation to that observed in those who underwent the sham procedure. However, we found no difference between the two groups in terms of the clinical parameters evaluated.<br><br>CONCLUSION: There were no significant differences in biochemical or anthropometric parameters, between the two groups evaluated. Nevertheless, there were significant postprocedural differences in the microbiota composition between the placebo group. To date, clinical outcomes related to FMT remain uncertain.}, }
@article {pmid37469558, year = {2023}, author = {Tian, E and Wang, F and Zhao, L and Sun, Y and Yang, J}, title = {The pathogenic role of intestinal flora metabolites in diabetic nephropathy.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1231621}, pmid = {37469558}, issn = {1664-042X}, abstract = {With the increasing incidence of diabetes, diabetic kidney disease has become a major cause of chronic kidney disease. The role of the gut microbiota in diabetes and its related complications have been extensively investigated; the modulatory effect of the gut microbiota on the host depends on several gut microbial metabolites, particularly short-chain fatty acids, secondary bile acids, and trimethylamine N-oxide. In this review, we focused on the evidence related to the pathogenic role of each of the gut microbial metabolites in diabetic nephropathy. The main novel therapies targeting the gut microbiota include probiotics, dietary prebiotics, synbiotic supplements, and faecal microbiota transplants, although there is no standard treatment principle. Further research is therefore needed to elucidate the link between gut microbes and diabetic nephropathy, and more therapeutic targets should be explored to treat diabetic nephropathy with dysbiosis of the gut microbes.}, }
@article {pmid37469017, year = {2023}, author = {Tian, H and Cui, J and Ye, C and Zhao, J and Yang, B and Xu, Y and Ji, S and Wang, L and Lv, X and Ma, C and Zhou, S and Li, N and Wang, X and Qin, H and Chen, Q}, title = {Depletion of butyrate-producing microbes of the Firmicutes predicts nonresponse to FMT therapy in patients with recurrent Clostridium difficile infection.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2236362}, pmid = {37469017}, issn = {1949-0984}, mesh = {Humans ; Fecal Microbiota Transplantation ; Firmicutes ; *Clostridioides difficile/physiology ; *Gastrointestinal Microbiome ; Feces/microbiology ; *Clostridium Infections/therapy/microbiology ; Butyrates ; Treatment Outcome ; }, abstract = {Approximately 10% of individuals diagnosed with Clostridium difficile infection (CDI) show the resistance to fecal microbiota transplantation (FMT), with the underlying mechanisms remaining elusive. Deciphering the intricate microbiome profile within this particular subset of FMT-refractory patients via clinical FMT investigations assumes paramount importance, as it holds the key to designing targeted therapeutic interventions tailored for CDI, particularly recurrent CDI (rCDI). A cohort of twenty-three patients afflicted with rCDI, exhibiting congruent clinical baselines, was meticulously selected for FMT. Rigorous screening of thousands of healthy individuals identified ten FMT donors who met stringent health standards, while a total of 171 stool samples were collected to serve as healthy controls. To assess the influence of microbiome dynamics on FMT efficacy, fecal samples were collected from four donors over a continuous period of twenty-five weeks. After FMT treatment, seven individuals exhibited an inadequate response to FMT. These non-remission patients displayed a significant reduction in α-diversity indexes. Meanwhile, prior to FMT, the abundance of key butyrate-producing Firmicutes bacteria, including Christensenellaceae_R_7_group, Ruminococcaceae_unclassified, Coprococcus_2, Fusicatenibacter, Oscillospira, and Roseburia, were depleted in non-remission patients. Moreover, Burkholderiales_unclassified, Coprococcus_2, and Oscillospira failed to colonize non-remission patients both pre- and post-treatment. Conversely, patients with a favorable FMT response exhibited a higher relative abundance of Veillonella prior to treatment, whereas its depletion was commonly observed in non-remission individuals. Genera interactions in lower effectiveness FMT donors were more similar to those in non-remission patients, and Burkholderiales_unclassified, Coprococcus_2, and Oscillospira were frequently depleted in these lower effectiveness donors. Older patients were not conducive to the colonization of Veillonella, consistent with their poor prognosis after FMT. FMT non-remission rCDI patients exhibited distinct characteristics that hindered the colonization of beneficial butyrate-producing Firmicutes microbes. These findings hold promise in advancing the precision of FMT therapy for rCDI patients.}, }
@article {pmid37467715, year = {2023}, author = {Jarosch, S and Köhlen, J and Ghimire, S and Orberg, ET and Hammel, M and Gaag, D and Evert, M and Janssen, KP and Hiergeist, A and Gessner, A and Weber, D and Meedt, E and Poeck, H and D'Ippolito, E and Holler, E and Busch, DH}, title = {Multimodal immune cell phenotyping in GI biopsies reveals microbiome-related T cell modulations in human GvHD.}, journal = {Cell reports. Medicine}, volume = {4}, number = {7}, pages = {101125}, pmid = {37467715}, issn = {2666-3791}, mesh = {Humans ; *Graft vs Host Disease/pathology ; *Microbiota/genetics ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Gastrointestinal Tract/pathology ; CD8-Positive T-Lymphocytes/pathology ; }, abstract = {Acute graft-versus-host disease (aGvHD) is a significant complication after allogeneic hematopoietic stem cell transplantation (aHSCT), but major factors determining disease severity are not well defined yet. By combining multiplexed tissue imaging and single-cell RNA sequencing on gastrointestinal biopsies from aHSCT-treated individuals with fecal microbiome analysis, we link high microbiome diversity and the abundance of short-chain fatty acid-producing bacteria to the sustenance of suppressive regulatory T cells (Tregs). Furthermore, aGvHD severity strongly associates with the clonal expansion of mainly CD8 T cells, which we find distributed over anatomically distant regions of the gut, persistent over time, and inversely correlated with the presence of suppressive Tregs. Overall, our study highlights the pathophysiological importance of expanded CD8 T cell clones in the progression of aGvHD toward more severe clinical manifestations and strongly supports the further development of microbiome interventions as GvHD treatment via repopulation of the gut Treg niche to suppress inflammation.}, }
@article {pmid37464825, year = {2023}, author = {Moghadam, MT and Ramírez-Coronel, AA and Darijani, S and Akbarizadeh, MR and Naderifar, M and Soltaninejad, S and Shahbazi, S and Dousari, AS and Mojtahedi, A and Akhavan-Sigari, R}, title = {Perturbations in Microbiota Composition as a Novel Mediator in Neuropsychiatric, Neurological and Mental Disorders: Preventive and Therapeutic Complementary Therapies to Balance the Change.}, journal = {Current Alzheimer research}, volume = {20}, number = {4}, pages = {213-223}, doi = {10.2174/1567205020666230718160914}, pmid = {37464825}, issn = {1875-5828}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Probiotics ; *Microbiota ; *Mental Disorders/prevention &amp; control ; *Nervous System Diseases/therapy ; *Complementary Therapies ; }, abstract = {Although microbiology and neurology are separate disciplines, they are linked to some infectious and neurological diseases. Today, microbiome is considered as one of the biomarkers of health by many researchers. This has led to the association of microbiome changes with many neurological diseases. The natural microbiota has many beneficial properties. If disrupted and altered, it can lead to irreversible complications and many neurological diseases. Therefore, according to previous studies, some preventive and therapeutic complementary therapies can prevent or restore microbiome dysbiosis and inflammation in the nervous system. With our current perception of the microbiological basis for different neurological disorders, both aspects of drug treatment and control of perturbations of the microbiome should be considered, and targeting them simultaneously will likely help to attain favorable results.}, }
@article {pmid37460073, year = {2023}, author = {Fang, J and Li, YX and Luo, HY and Zhang, WH and Chan, KC and Chan, YM and Chen, HB and Zhao, ZZ and Li, SL and Dong, CX and Xu, J}, title = {Impacts of sulfur fumigation on the chemistry and immunomodulatory activity of polysaccharides in ginseng.}, journal = {International journal of biological macromolecules}, volume = {247}, number = {}, pages = {125843}, doi = {10.1016/j.ijbiomac.2023.125843}, pmid = {37460073}, issn = {1879-0003}, mesh = {Mice ; Animals ; *Panax/chemistry ; Fumigation ; Sulfur/chemistry ; Polysaccharides/pharmacology ; Plant Extracts ; }, abstract = {Ginseng is widely regarded as a panacea in Oriental medicine mainly due to its immunomodulatory activity. We previously found that sulfur fumigation, a commonly used pesticidal and anti-bacterial processing practice, weakened the immunomodulatory activity of ginseng. However, if and how sulfur fumigation affects the polysaccharides in ginseng, the crucial components contributing to the immunomodulatory function, remain unknown. Here we report that polysaccharides extracted from sulfur-fumigated ginseng (SGP) presented different chemical properties with polysaccharides extracted with non-fumigated ginseng (NGP), particularly increased water extraction yield and decreased branching degree. SGP had weaker immunomodulatory activity than NGP in immunocompromised mice, as evidenced by less improved immunophenotypes involving body weight, immune organ indexes, white blood cells, lymphocyte cell populations and inflammation. The different immunomodulatory activities were accompanied by changes in the interaction between the polysaccharides and gut microbiota, in which SGP stimulated the growth of different bacteria but produced less SCFAs as compared to NGP. Fecal microbiota transplantation experiment suggested that gut microbiota played a central role in causing the weakened immunomodulatory activity in vivo. This study provides definite evidence that sulfur fumigation affects the chemistry and bioactivity of ginseng polysaccharides, thereby contributing to understanding how sulfur fumigation weakens the immunomodulatory activity of ginseng.}, }
@article {pmid37458581, year = {2023}, author = {Montalto, M and Gallo, A and Agnitelli, MC and Pellegrino, S and Lipari, A and Pero, E and Covino, M and Landi, F and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile infection in frail and very old patients.}, journal = {Journal of the American Geriatrics Society}, volume = {71}, number = {11}, pages = {3530-3537}, doi = {10.1111/jgs.18500}, pmid = {37458581}, issn = {1532-5415}, support = {//Italian Ministry of Health-Ricerca Corrente 2023 and European Union-Next Generation EU (AGE-IT)/ ; }, mesh = {Humans ; Aged ; Aged, 80 and over ; Fecal Microbiota Transplantation/adverse effects/methods ; Retrospective Studies ; Frail Elderly ; *Frailty/therapy/etiology ; Reproducibility of Results ; Treatment Outcome ; *Clostridioides difficile ; Recurrence ; *Clostridium Infections/drug therapy ; }, abstract = {BACKGROUND: Older age is a well-known risk factor for recurrent and severe Clostridioides difficile infection (CDI). Fecal microbiota transplantation (FMT) is widely recognized as an effective and safe therapeutic option for the treatment of recurrent CDI (rCDI). However, the efficacy and safety of FMT for rCDI in very old patients are uncertain. This study evaluated the efficacy and safety of FMT in a group of very old subjects with rCDI, and the reliability of overall comorbidity and frailty assessment for identifying patients at higher risk of worse clinical outcomes.<br><br>METHODS: This is a retrospective single-center study including patients &#x2265;85&#x2009;years undergoing FMT for rCDI between 2014 and 2022. Primary outcomes included efficacy of FMT, defined as cure of CDI at 8&#x2009;week-follow-up, and safety evaluation. At baseline, comorbidity was measured with the Charlson Comorbidity Index (CCI). Frailty was measured with the Clinical Frailty Scale (CFS).<br><br>RESULTS: Overall, 43 patients with a median age of 88&#x2009;years underwent FMT by colonoscopy in the study period. The rate of first FMT success was 77%. Five of the 10 patients who failed the first FMT infusion were cured after repeat FMT, with an overall efficacy of 88%. In patients with successful treatment, the CFS was significantly lower compared to those who failed the FMT or underwent repeat FMT (p&#x2009;<&#x2009;0.01 for both). Mild adverse events occurred in 11 patients (25%). One death, not related to FMT or rCDI, occurred within 7&#x2009;days from the first procedure.<br><br>CONCLUSIONS: FMT is effective and safe in very old patients. Frailty and high comorbidity do not limit use of FMT in these patients. Frailty assessment has potential to better identify patients at higher risk of worse outcomes or for repeat treatment with FMT.}, }
@article {pmid37457968, year = {2023}, author = {Fatani, AMN and Suh, JH and Auger, J and Alabasi, KM and Wang, Y and Segal, MS and Dahl, WJ}, title = {Pea hull fiber supplementation does not modulate uremic metabolites in adults receiving hemodialysis: a randomized, double-blind, controlled trial.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1179295}, pmid = {37457968}, issn = {2296-861X}, abstract = {BACKGROUND: Fiber is a potential therapeutic to suppress microbiota-generated uremic molecules. This study aimed to determine if fiber supplementation decreased serum levels of uremic molecules through the modulation of gut microbiota in adults undergoing hemodialysis.<br><br>METHODS: A randomized, double-blinded, controlled crossover study was conducted. Following a 1-week baseline, participants consumed muffins with added pea hull fiber (PHF) (15&#x2009;g/d) and control muffins daily, each for 4 weeks, separated by a 4-week washout. Blood and stool samples were collected per period. Serum p-cresyl sulfate (PCS), indoxyl sulfate (IS), phenylacetylglutamine (PAG), and trimethylamine N-oxide (TMAO) were quantified by LC-MS/MS, and fecal microbiota profiled by 16S rRNA gene amplicon sequencing and specific taxa of interest by qPCR. QIIME 2 sample-classifier was used to discover unique microbiota profiles due to the consumption of PHF.<br><br>RESULTS: Intake of PHF contributed an additional 9&#x2009;g/d of dietary fiber to the subjects' diet due to compliance. No significant changes from baseline were observed in serum PCS, IS, PAG, or TMAO, or for the relative quantification of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bifidobacterium, or Roseburia, taxa considered health-enhancing. Dietary protein intake and IS (r&#x2009;=&#x2009;-0.5, p&#x2009;=&#x2009;0.05) and slow transit stool form and PCS (r&#x2009;=&#x2009;0.7, p&#x2009;<&#x2009;0.01) were significantly correlated at baseline. PHF and control periods were not differentiated; however, using machine learning, taxa most distinguishing the microbiota composition during the PHF periods compared to usual diet alone were enriched Gemmiger, Collinsella, and depleted Lactobacillus, Ruminococcus, Coprococcus, and Mogibacteriaceae.<br><br>CONCLUSION: PHF supplementation did not mitigate serum levels of targeted microbial-generated uremic molecules. Given the high cellulose content, which may be resistant to fermentation, PHF may not exert sufficient effects on microbiota composition to modulate its activity at the dose consumed.}, }
@article {pmid37457967, year = {2023}, author = {Cao, C and Shi, M and Wang, X and Yao, Y and Zeng, R}, title = {Effects of probiotics on non-alcoholic fatty liver disease: a review of human clinical trials.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1155306}, pmid = {37457967}, issn = {2296-861X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a global public health issue, of which the prevalence is about 25% worldwide. The incidence of NAFLD is increasing in patients with obesity, type 2 diabetes (T2DM) and the metabolic syndrome. The crosstalk between gut microbiota and metabolism-related diseases has been raised great concern. Patients with NAPLD were observed with disruption of gut microbiota. Several researches showed that gut microbiota was the determination in the progression of NAFLD by the experiments using fecal microbiota transplants. The application of probiotics, as one of the most important strategies for the regulation of gut microbiota disorder, have been explored whether it is beneficial to gut-related diseases of intestine-distal organs. Some probiotics were showed to improve the liver parameters and phenotype in patients with NAFLD. The oral intake of them might become the effective management for the prevention and treatment of NAFLD. In this review, we summarized the human clinical trials focusing on the effects of probiotics on NAFLD to give some evidential reference for the administration of NAFLD.}, }
@article {pmid37454252, year = {2023}, author = {Jun, Z and Junhua, W and Xiaobing, LI and Chenyi, W and Fangjun, LI and Yanni, L and Hao, C and Meiying, S}, title = {Efficacy of Heshouwu () on gut mircobiota in mice with autoimmune encephalomyelitis.}, journal = {Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan}, volume = {43}, number = {4}, pages = {676-685}, pmid = {37454252}, issn = {2589-451X}, support = {82101419//National Natural Science Foundation of China: Role and Mechanism of Akkermansia-Mediated Activation of Microglia NLRP3 Inflammasome in Multiple Sclerosis/ ; 20212BAB216024//Jiangxi Provincial Natural Science Foundation: the Role and Mechanism of p38 MAPK Signaling Pathway Induced by Intestinal Flora Change in EAE Mice/ ; 2021B660//Jiangxi Science and Technology Project of Chinese Medicine: Study on the Role and Mechanism of CGAS-STING Signaling Pathway in Microglia Mediated by Rhodiola Sachalinensis in Multiple Sclerosis/ ; 2022B1007//Jiangxi Science and Technology Project of Chinese Medicine: Study on the Role and Mechanism of CGAS-STING Signaling Pathway in Microglia Mediated by Rhodiola Sachalinensis in Multiple Sclerosis/ ; 202210392//Jiangxi Science and Technology Program of Health Commission: the Role and Mechanism of Intestinal Flora Changes in Mediating the Activation of NLRP3 Inflammasome in Microglia in Multiple Sclerosis/ ; GJJ200215//Science and Technology Research Project of Jiangxi Education: Study on the Role and Mechanism of p38 MAPK Signaling Pathway Induced by Intestinal Flora Changes in EAE Mice/ ; YFYPY202021//Scientific Research and Development Project of the First Affiliated Hospital of Nanchang University: Effects of Exercise Training on Intestinal Flora of Multiple Sclerosis Model Rats and Its Mechanism/ ; }, mesh = {Mice ; Animals ; Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use ; RNA, Ribosomal, 16S ; *Encephalomyelitis, Autoimmune, Experimental/drug therapy/genetics ; Spinal Cord/pathology ; *Encephalomyelitis/pathology ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVE: To learn the mechanisms between gut microbiome and the autoimmunity benefits on Traditional Chinese Medicine (TCM) in central nervous system (CNS), we investigated the neuro-protection effects and gut mircobiota changes of Heshouwu () on experimental autoimmune encepha-lomyelitis (EAE), an animal model of multiple sclerosis (MS).<br><br>METHODS: Mice were randomly divided into four groups: EAE mice (control phosphate-buffered saline group), 50 mg&#xb7;kg&#xb7;d Heshouwu ()-treated EAE mice, 100 mg&#xb7;kg&#xb7;d Heshouwu ()-treated EAE mice, and 200 mg&#xb7;kg&#xb7;d Heshouwu ()-treated EAE mice. The spinal cords were stained with hematoxylin and eosin (HE) and luxol fast blue for evaluating inflammatory infiltration and demyelination. The percentages of granulocyte macrophage-colony stimulating factor (GM-CSF)+CD4+, interleukin 17 (IL-17)+CD4+, Foxp3 CD4+, and interferon-&#x3b3; (IFN-&#x3b3;)+CD4+ T cells in the inguinal lymph nodes (LNs) and brain were determined by flow cytometry analysis. 16S rRNA gene sequencing was employed to analyze the changes in gut microbiota.<br><br>RESULTS: We found that Heshouwu () alleviated the disease severity and neuropathology of EAE as evaluated by clinical and histopathologyical scores. Heshouwu () increased the diversity and abundance of the gut microbiota, and decreased / ratio (F/B ratio). Heshouwu () also decreased the concentrations of IL-10, and IL-21 and increase the levels of GM-CSF, IL-17A, IL-17F and IL-22 in serum of EAE mice. Moreover, Heshouwu () modulated the T cell responses by inhibiting Th17 cells and restoring Treg cells in the small intestine lymphoid tissues and inguinal lymph nodes. Microbiota-depleted mice receiving Heshouwu ()-treated fecal microbiota trans-plantation had lower disease severity, neuropathology scores and alleviation of Th17/Treg imbalance compared to ad libitum group.<br><br>CONCLUSIONS: Our findings suggested that the vital neuro-protection role of Heshouwu () (TCM) in immunomodulation effects partly by regulations of gut microbiome.}, }
@article {pmid37454113, year = {2023}, author = {Zheng, H and Zhao, Q and Chen, J and Lu, J and Li, Y and Gao, H}, title = {Gastrointestinal microbiome of ARDS patients induces neuroinflammation and cognitive impairment in mice.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {166}, pmid = {37454113}, issn = {1742-2094}, support = {22074106//National Natural Science Foundation of China/ ; 21974096//National Natural Science Foundation of China/ ; }, mesh = {Male ; Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Neuroinflammatory Diseases ; RNA, Ribosomal, 16S/genetics ; Quality of Life ; *Cognitive Dysfunction ; *Pneumonia ; *Respiratory Distress Syndrome/microbiology ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Acute respiratory distress syndrome (ARDS) is a respiratory failure syndrome that can cause many complications, impacting patients' quality of life. Behavioral and cognitive disorders have attracted increasing attention in patients with ARDS, but its potential mechanisms are still elusive.<br><br>METHODS: Herein we transferred the faecal microbiota from patients with ARDS caused by community-acquired pneumonia (CAP) to antibiotics-treated recipient male mice to explore the microbiota-gut-brain mechanisms. Behavioral functions of mice were evaluated by the open field test, Morris water maze and Y-maze test. The structure and composition of the gut microbiota were analyzed by using 16S rRNA sequencing analysis. Microglia, astrocyte&#xa0;and neuron in the cortex and hippocampus were examined via immunofluorescent staining.<br><br>RESULTS: We found that the major characteristic of the intestinal flora in ARDS/CAP patients was higher abundances of Gram-negative bacteria than normal controls. The gut microbiota derived from ARDS/CAP patients promoted neuroinflammation and behavioral dysfunctions in mice. Mice who underwent fecal transplant from ARDS/CAP patients had increased systemic lipopolysaccharide&#xa0;(LPS), systemic inflammation, and increased colonic barrier permeability. This may adversely impact blood barrier permeability and facilitate microglia activation, astrocyte proliferation, and loss of neurons.<br><br>CONCLUSIONS: Our study proposes the role of the microbiota-gut-brain crosstalk on ARDS/CAP-associated behavioral impairments and suggests the gut microbiota as a potential target for the protection of brain health in ARDS patients in clinical practice.}, }
@article {pmid37453856, year = {2023}, author = {Jiang, L and Xu, J and Cheng, SY and Wang, Y and Cai, W}, title = {The gut microbiome and intestinal failure-associated liver disease.}, journal = {Hepatobiliary &amp; pancreatic diseases international : HBPD INT}, volume = {22}, number = {5}, pages = {452-457}, doi = {10.1016/j.hbpd.2023.07.002}, pmid = {37453856}, issn = {1499-3872}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Intestinal Failure ; *Liver Diseases/etiology ; *Intestinal Diseases/complications ; *Liver Failure/complications ; *Hypertension, Portal/complications ; }, abstract = {Intestinal failure-associated liver disease (IFALD) is a common hepatobiliary complication resulting from long-term parenteral nutrition (PN) in patients with intestinal failure. The spectrum of IFALD ranges from cholestasis, steatosis, portal fibrosis, to cirrhosis. Development of IFALD is a multifactorial process, in which gut dysbiosis plays a critical role in its initiation and progression in conjunction with increased intestinal permeability, activation of hepatic immune responses, and administration of lipid emulsion. Gut microbiota manipulation including pre/probiotics, fecal microbiota transplantation, and antibiotics has been studied in IFALD with varying success. In this review, we summarize current knowledge on the taxonomic and functional changes of gut microbiota in preclinical and clinical studies of IFALD. We also review the function of microbial metabolites and associated signalings in the context of IFALD. By providing microbiota-targeted interventions aiming to optimize PN-induced liver injury, our review provides perspectives for future basic and translational investigations in the field.}, }
@article {pmid37451630, year = {2023}, author = {Zhang, X and Cremers, N and Hendrickx, S and Debing, Y and Roskams, T and Coelmont, L and Neyts, J and Kaptein, SJF}, title = {Establishment of a robust rat hepatitis E virus fecal-oral infection model and validation for antiviral studies.}, journal = {Antiviral research}, volume = {216}, number = {}, pages = {105670}, doi = {10.1016/j.antiviral.2023.105670}, pmid = {37451630}, issn = {1872-9096}, mesh = {Animals ; Rats ; Humans ; *Hepatitis E virus ; Antiviral Agents/pharmacology/therapeutic use ; Ribavirin/pharmacology/therapeutic use ; *Hepatitis E/drug therapy ; RNA, Viral/genetics ; Feces ; }, abstract = {The hepatitis E virus (HEV) is a major cause of hepatitis, with an estimated 3.3 million symptomatic cases annually. There is no HEV-specific treatment besides the off-label use of ribavirin and a vaccine is only available in China and Pakistan. To aid the development of therapeutic and preventive strategies, there is a need for convenient HEV infection models in small laboratory animals. To this end, we make use of the rat hepatitis E virus. Human infections with this virus have been reported in recent years, making it a relevant pathogen for the establishment of a small animal infection model. We here report that oral gavage of a feces suspension, containing a pre-defined viral RNA load, results in a reproducible synchronized infection in athymic nude rats. This route of administration mimics fecal-oral transmission in a standardized fashion. The suitability of the model to study the effect of antiviral drugs was assessed by using ribavirin, which significantly reduced viral loads in the feces, liver, and other tissues.}, }
@article {pmid37451270, year = {2023}, author = {Yang, J and Yang, X and Wu, G and Huang, F and Shi, X and Wei, W and Zhang, Y and Zhang, H and Cheng, L and Yu, L and Shang, J and Lv, Y and Wang, X and Zhai, R and Li, P and Cui, B and Fang, Y and Deng, X and Tang, S and Wang, L and Yuan, Q and Zhao, L and Zhang, F and Zhang, C and Yuan, H}, title = {Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes.}, journal = {Cell metabolism}, volume = {35}, number = {9}, pages = {1548-1562.e7}, doi = {10.1016/j.cmet.2023.06.010}, pmid = {37451270}, issn = {1932-7420}, mesh = {*Diabetic Neuropathies/drug therapy/etiology/pathology ; *Gastrointestinal Microbiome ; *Polyneuropathies/complications ; Humans ; }, abstract = {The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood. Here, we discover that the gut microbiota from patients with DSPN can induce a phenotype exhibiting more severe peripheral neuropathy in db/db mice. In a randomized, double-blind, and placebo-controlled trial (ChiCTR1800017257), compared to 10 patients who received placebo, DSPN was significantly alleviated in the 22 patients who received fecal microbiota transplants from healthy donors, independent of glycemic control. The gut bacterial genomes that correlated with the Toronto Clinical Scoring System (TCSS) score were organized in two competing guilds. Increased guild 1, which had higher capacity in butyrate production, and decreased guild 2, which harbored more genes in synthetic pathway of endotoxin, were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched guild 1 and suppressed guild 2. Thus, changes in these two competing guilds may play a causative role in DSPN and have the potential for therapeutic targeting.}, }
@article {pmid37450947, year = {2024}, author = {Zaman, S and Akingboye, A and Mohamedahmed, AYY and Peterknecht, E and Bhattacharya, P and El-Asrag, ME and Iqbal, TH and Quraishi, MN and Beggs, AD}, title = {Faecal Microbiota Transplantation [FMT] in the Treatment of Chronic Refractory Pouchitis: A Systematic Review and Meta-analysis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {18}, number = {1}, pages = {144-161}, pmid = {37450947}, issn = {1876-4479}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Pouchitis/therapy/etiology ; Quality of Life ; Remission Induction ; *Gastrointestinal Microbiome ; Treatment Outcome ; Feces ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: The aim of this systematic review and meta-analysis is to assess the efficacy and safety of faecal microbiota transplantation [FMT] in the treatment of chronic pouchitis.<br><br>METHODS: A PRISMA-compliant systematic review and meta-analysis was conducted using the following databases and clinical trial registers: Medline, Embase, Scopus, Cochrane Database of Systematic Reviews [CENTRAL], clinical trials.gov, ScienceDirect, and VHL [virtual health library]. The primary outcome was clinical response/remission in patients treated with FMT. Secondary outcomes included safety profile, quality of life, and changes in the gut microbiome.<br><br>RESULTS: Seven observational cohort studies/case series and two randomised, controlled trials with a total of 103 patients were included. The route, preparation, and quantity of FMT administered varied among the included studies. Clinical response rate of 42.6% with a remission rate of 29.8% was estimated in our cohort following FMT therapy. Minor, self-limiting, adverse events were reported, and the treatment was well tolerated with good short- and long-term safety profiles. Successful FMT engraftment in recipients varied and, on average, microbial richness and diversity was lower in patients with pouchitis. In some instances, shifts with specific changes towards abundance of species, suggestive of a 'healthier' pouch microbiota, were observed following treatment with FMT.<br><br>CONCLUSION: The evidence for FMT in the treatment of chronic pouchitis is sparse, which limits any recommendations being made for its use in clinical practice. Current evidence from low-quality studies suggests a variable clinical response and remission rate, but the treatment is well tolerated, with a good safety profile. This review emphasises the need for rationally designed, well-powered, randomised, placebo-controlled trials to understand the efficacy of FMT for the treatment of pouchitis.}, }
@article {pmid37450589, year = {2023}, author = {Shi, B and Zhang, X and Song, Z and Dai, Z and Luo, K and Chen, B and Zhou, Z and Cui, Y and Feng, B and Zhu, Z and Zheng, J and Zhang, H and He, X}, title = {Targeting gut microbiota-derived kynurenine to predict and protect the remodeling of the pressure-overloaded young heart.}, journal = {Science advances}, volume = {9}, number = {28}, pages = {eadg7417}, pmid = {37450589}, issn = {2375-2548}, mesh = {Animals ; Mice ; *Kynurenine/metabolism ; *Gastrointestinal Microbiome ; Heart ; Fibroblasts/metabolism ; Metabolomics ; }, abstract = {Pressure-overloaded left ventricular remodeling in young population is progressive and readily degenerate into heart failure. The aims of this study were to identify a plasma metabolite that predicts and is mechanistically linked to the disease. Untargeted metabolomics determined elevated plasma kynurenine (Kyn) in both the patient cohorts and the mice model, which was correlated with remodeling parameters. In vitro and in vivo evidence, combined with single-nucleus RNA sequencing (snRNA-seq), demonstrated that Kyn affected both cardiomyocytes and cardiac fibroblasts by activating aryl hydrocarbon receptors (AHR) to up-regulate hypertrophy- and fibrosis-related genes. Shotgun metagenomics and fecal microbiota transplantation revealed the existence of the altered gut microbiota-Kyn relationship. Supplementation of selected microbes reconstructed the gut microbiota, reduced plasma Kyn, and alleviated ventricular remodeling. Our data collectively discovered a gut microbiota-derived metabolite to activate AHR and its gene targets in remodeling young heart, a process that could be prevented by specific gut microbiota modulation.}, }
@article {pmid37449731, year = {2023}, author = {}, title = {Fecal Microbiota Transplantation plus Anti-PD-1 Is Safe in a First-line Setting.}, journal = {Cancer discovery}, volume = {13}, number = {9}, pages = {1957}, doi = {10.1158/2159-8290.CD-RW2023-109}, pmid = {37449731}, issn = {2159-8290}, mesh = {Humans ; *Fecal Microbiota Transplantation ; }, abstract = {Fecal microbiota transplantation combined with anti-PD-1 is safe in melanoma in the first-line setting.}, }
@article {pmid37446647, year = {2023}, author = {Yan, X and Li, J and Wu, D}, title = {The Role of Short-Chain Fatty Acids in Acute Pancreatitis.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {13}, pages = {}, pmid = {37446647}, issn = {1420-3049}, support = {32170788//National Natural Science Foundation of China/ ; 2022-PUMCH-B-023//National High Level Hospital Clinical Research Funding/ ; ZK108000//National Key Clinical Specialty Construction Project/ ; 7232123//Beijing Natural Science Foundation/ ; }, mesh = {Humans ; *Pancreatitis/therapy ; Acute Disease ; Fatty Acids, Volatile/metabolism ; Butyrates ; Inflammation/metabolism ; }, abstract = {Acute pancreatitis (AP) is a digestive emergency and can develop into a systematic illness. The role of the gut in the progression and deterioration of AP has drawn much attention from researchers, and areas of interest include dysbiosis of the intestinal flora, weakened intestinal barrier function, and bacterial and endotoxin translocation. Short-chain fatty acids (SCFAs), as one of the metabolites of gut microbiota, have been proven to be depleted in AP patients. SCFAs help restore gut homeostasis by rebuilding gut flora, stabilizing the intestinal epithelial barrier, and regulating inflammation. SCFAs can also suppress systematic inflammatory responses, improve the injured pancreas, and prevent and protect other organ dysfunctions. Based on multiple beneficial effects, increasing SCFAs is an essential idea of gut protective treatment in AP. Specific strategies include the direct use of butyrate or indirect supplementation through fiber, pre/pro/synbiotics, or fecal microbiota transplantation as a promising adjective therapy to enteral nutrition.}, }
@article {pmid37446182, year = {2023}, author = {Zhu, M and Song, Y and Xu, Y and Xu, H}, title = {Manipulating Microbiota in Inflammatory Bowel Disease Treatment: Clinical and Natural Product Interventions Explored.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37446182}, issn = {1422-0067}, support = {U1902213//the NSFC-Joint Foundation of Yunnan Province/ ; 2020B1111110003//the Guangdong Province Key Area R&amp;D Program of China/ ; }, mesh = {Humans ; *Inflammatory Bowel Diseases/drug therapy ; *Colitis, Ulcerative ; *Crohn Disease/drug therapy ; Intestines ; *Microbiota ; }, abstract = {Inflammatory bowel disease (IBD) is a complex multifactorial chronic inflammatory disease, that includes Crohn's disease (CD) and ulcerative colitis (UC), having progressively increasing global incidence. Disturbed intestinal flora has been highlighted as an important feature of IBD and offers promising strategies for IBD remedies. A brief overview of the variations occurring in intestinal flora during IBD is presented, and the role of the gut microbiota in intestinal barrier maintenance, immune and metabolic regulation, and the absorption and supply of nutrients is reviewed. More importantly, we review drug research on gut microbiota in the past ten years, including research on clinical and natural drugs, as well as adjuvant therapies, such as Fecal Microbiota Transplantation and probiotic supplements. We also summarize the interventions and mechanisms of these drugs on gut microbiota.}, }
@article {pmid37444223, year = {2023}, author = {Ang, WS and Law, JW and Letchumanan, V and Hong, KW and Wong, SH and Ab Mutalib, NS and Chan, KG and Lee, LH and Tan, LT}, title = {A Keystone Gut Bacterium Christensenella minuta-A Potential Biotherapeutic Agent for Obesity and Associated Metabolic Diseases.}, journal = {Foods (Basel, Switzerland)}, volume = {12}, number = {13}, pages = {}, pmid = {37444223}, issn = {2304-8158}, support = {ECR-000039//Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia/ ; }, abstract = {A new next-generation probiotic, Christensenella minuta was first discovered in 2012 from healthy human stool and described under the phylum Firmicutes. C. minuta is a subdominant commensal bacterium with highly heritable properties that exhibits mutual interactions with other heritable microbiomes, and its relative abundance is positively correlated with the lean host phenotype associated with a low BMI index. It has been the subject of numerous studies, owing to its potential health benefits. This article reviews the evidence from various studies of C. minuta interventions using animal models for managing metabolic diseases, such as obesity, inflammatory bowel disease, and type 2 diabetes, characterized by gut microbiota dysbiosis and disruption of host metabolism. Notably, more studies have presented the complex interaction between C. minuta and host metabolism when it comes to metabolic health. Therefore, C. minuta could be a potential candidate for innovative microbiome-based biotherapy via fecal microbiota transplantation or oral administration. However, the detailed underlying mechanism of action requires further investigation.}, }
@article {pmid37443082, year = {2023}, author = {Zhang, H and Zheng, L and Li, C and Jing, J and Li, Z and Sun, S and Xue, T and Zhang, K and Xue, M and Cao, C and Ouyang, L and Qian, Z and Xu, R and He, Z and Ma, R and Chen, L and Yao, B}, title = {Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice.}, journal = {Journal of ovarian research}, volume = {16}, number = {1}, pages = {138}, pmid = {37443082}, issn = {1757-2215}, support = {82271687//National Natural Science Foundation of China/ ; 82274651//National Natural Science Foundation of China/ ; BE2022712//Jiangsu Provincial Key Research and Development Program/ ; ZD2022004//Key Medical Research Projects of Jiangsu Provincial Health Commission/ ; }, mesh = {Animals ; Female ; Mice ; Dehydroepiandrosterone/toxicity ; *Gastrointestinal Microbiome/physiology ; Insulin Resistance ; *Polycystic Ovary Syndrome/chemically induced/drug therapy/physiopathology ; *Fatty Acids, Omega-3/therapeutic use ; *Dietary Supplements ; }, abstract = {BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota.<br><br>METHODS: We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated.<br><br>RESULTS: We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1&#x3b2;, TNF-&#x3b1; and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues.<br><br>CONCLUSION: These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.}, }
@article {pmid37442498, year = {2023}, author = {Keubler, LM and Talbot, SR and Bleich, A and Boyle, EC}, title = {Systematic review and meta-analysis of the effect of fecal microbiota transplantation on behavior in animals.}, journal = {Neuroscience and biobehavioral reviews}, volume = {153}, number = {}, pages = {105316}, doi = {10.1016/j.neubiorev.2023.105316}, pmid = {37442498}, issn = {1873-7528}, abstract = {The bi-directional interaction between gut microbiota and the central nervous system has been coined the gut microbiota-brain axis. Fecal microbiota transplantation (FMT) is the administration of a solution of fecal matter from a donor into the intestinal tract of a recipient. Preclinical FMT experiments are essential to prove causality in the context of the gut microbiota-brain axis. In this systematic review, we assess the body of evidence related to the ability of FMT to modulate an animal's behavior. Accordingly, we provide a detailed summary of the use of FMT in behavior-related animal studies, an extensive risk of bias analysis, and a meta-analysis of the overall effect of FMT on behavioral outcome measures in 64 studies, representing 4889 animals. The resulting meta-analysis revealed FMT was effective at changing animal behavior, thereby substantiating evidence for the gut microbiota-brain axis. However, our study also highlights an urgent need for methodological safeguards within this research field to reduce the risk of bias and improve the internal validity of future studies.}, }
@article {pmid37442219, year = {2023}, author = {Qi, D and Zou, S and Lu, D and Pei, X and Huang, S and Huang, DL and Liu, J and Si, H and Li, Z}, title = {Long-term high fructose intake promotes lacrimal gland dysfunction by inducing gut dysbiosis in mice.}, journal = {Experimental eye research}, volume = {234}, number = {}, pages = {109573}, doi = {10.1016/j.exer.2023.109573}, pmid = {37442219}, issn = {1096-0007}, mesh = {Mice ; Animals ; *Lacrimal Apparatus/metabolism ; Dysbiosis/metabolism ; RNA, Ribosomal, 16S/genetics ; *Gastrointestinal Microbiome ; Fructose/toxicity/metabolism ; }, abstract = {The lacrimal gland is essential for maintaining ocular surface health through the secretion of the aqueous layer of the tear film. It is therefore important to explore the intrinsic and extrinsic factors that affect the structure and function of the lacrimal gland and the mechanisms underlying them. With the prevalence of Westernized diets characterized by high sugar and fat content, the susceptibility to many diseases, including ocular diseases, is increased by inducing dysbiosis of the gut microbiome. Here, we found that the composition, abundance, and diversity of the gut microbiome was significantly altered in mice by drinking 15% high fructose water for one month, as determined by 16S rRNA sequencing. This was accompanied by a significant increase in lipid deposition and inflammatory cell infiltration in the extraorbital lacrimal glands (ELGs) of mice. Transcriptome analysis based on bulk RNA-sequencing revealed abnormal activation of some of several metabolic and immune-related pathways. In addition, the secretory response to stimulation with the cholinergic receptor agonist pilocarpine was significantly reduced. However, when the composition and diversity of the gut microbiome of high fructose intake (HFI)-treated mice were improved by transplanting feces from normal young healthy mice, the pathological alterations in ELG structure, inflammatory cell infiltration, secretory function and transcriptome analysis described above were significantly reversed compared to age-matched control mice. In conclusion, our data suggest that prolonged HFI may cause pathological damage to the structure and function of the ELG through the induction of gut dysbiosis. Restoration of intestinal dysbiosis in HFI-treated mice by fecal transplantation has a potential role in ameliorating these pathological impairments.}, }
@article {pmid37441951, year = {2023}, author = {Zhang, Y and Hou, B and Liu, T and Wu, Y and Wang, Z}, title = {Probiotics improve polystyrene microplastics-induced male reproductive toxicity in mice by alleviating inflammatory response.}, journal = {Ecotoxicology and environmental safety}, volume = {263}, number = {}, pages = {115248}, doi = {10.1016/j.ecoenv.2023.115248}, pmid = {37441951}, issn = {1090-2414}, mesh = {Male ; Animals ; Mice ; Microplastics ; Plastics ; Polystyrenes/toxicity ; Semen ; *Environmental Pollutants ; Lactobacillus ; *Probiotics/pharmacology ; }, abstract = {As a new type of environmental pollutant, microplastics have been garnered increasing attention, especially in regard to their effects on the reproductive system. However, researchers have yet to report whether prevention and treatment measures exist for reproductive injury caused by microplastics. The aim of this study was therefore to explore the mechanism of spermatogenic injury induced by polystyrene microplastics (PS-MPs) and the intervention effect of probiotics based on the gut microbiota-testis axis. Mice were orally exposed for 35 days to 5 µm of PS-MPs with a gavage dose was 0.1 mg/day, and the intervention group was given probiotics (Lactobacillus, Bifidobacterium longum, and Enterococcus) orally. Fecal samples were then subjected to 16 S rRNA sequencing analysis, and sperm motion was analyzed by a Hamilton-Thorne Sperm analyzer. The results showed that PS-MPs exposed mice had significant spermatogenic dysfunction and testicular inflammation. In addition, the intestinal microbial structure of exposed mice changed significantly; the abundance of Lactobacillus decreased, and the abundance of Prevotella increased. Furthermore, with fecal microbiota transplantation, the recipient mice showed a significant decrease in sperm quality. However, probiotics supplementation helped inhibit the activation of IL-17A signaling driven by gut microbes, thereby alleviating the inflammatory response and improving sperm quality decline caused by PS-MPs. These results may provide a scientific basis for further understanding of the mechanism of male reproductive damage caused by environmental pollutants such as microplastics and for novel reproductive damage intervention measures.}, }
@article {pmid37441494, year = {2023}, author = {Neri-Rosario, D and Martínez-López, YE and Esquivel-Hernández, DA and Sánchez-Castañeda, JP and Padron-Manrique, C and Vázquez-Jiménez, A and Giron-Villalobos, D and Resendis-Antonio, O}, title = {Dysbiosis signatures of gut microbiota and the progression of type 2 diabetes: a machine learning approach in a Mexican cohort.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1170459}, pmid = {37441494}, issn = {1664-2392}, mesh = {Humans ; *Diabetes Mellitus, Type 2/diagnosis ; *Gastrointestinal Microbiome ; *Prediabetic State/diagnosis ; Dysbiosis ; RNA, Ribosomal, 16S/genetics ; Machine Learning ; }, abstract = {INTRODUCTION: The gut microbiota (GM) dysbiosis is one of the causal factors for the progression of different chronic metabolic diseases, including type 2 diabetes mellitus (T2D). Understanding the basis that laid this association may lead to developing new therapeutic strategies for preventing and treating T2D, such as probiotics, prebiotics, and fecal microbiota transplants. It may also help identify potential early detection biomarkers and develop personalized interventions based on an individual's gut microbiota profile. Here, we explore how supervised Machine Learning (ML) methods help to distinguish taxa for individuals with prediabetes (prediabetes) or T2D.<br><br>METHODS: To this aim, we analyzed the GM profile (16s rRNA gene sequencing) in a cohort of 410 Mexican na&#xef;ve patients stratified into normoglycemic, prediabetes, and T2D individuals. Then, we compared six different ML algorithms and found that Random Forest had the highest predictive performance in classifying T2D and prediabetes patients versus controls.<br><br>RESULTS: We identified a set of taxa for predicting patients with T2D compared to normoglycemic individuals, including Allisonella, Slackia, Ruminococus_2, Megaspgaera, Escherichia/Shigella, and Prevotella, among them. Besides, we concluded that Anaerostipes, Intestinibacter, Prevotella_9, Blautia, Granulicatella, and Veillonella were the relevant genus in patients with prediabetes compared to normoglycemic subjects.<br><br>DISCUSSION: These findings allow us to postulate that GM is a distinctive signature in prediabetes and T2D patients during the development and progression of the disease. Our study highlights the role of GM and opens a window toward the rational design of new preventive and personalized strategies against the control of this disease.}, }
@article {pmid37441065, year = {2023}, author = {Yang, JW and Wan, S and Li, KP and Chen, SY and Yang, L}, title = {Gut and urinary microbiota: the causes and potential treatment measures of renal cell carcinoma.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1188520}, pmid = {37441065}, issn = {1664-3224}, mesh = {Male ; Humans ; *Carcinoma, Renal Cell/etiology/therapy ; *Microbiota ; *Gastrointestinal Microbiome ; *Prostatic Neoplasms ; *Kidney Neoplasms/etiology/therapy/pathology ; }, abstract = {Mounting evidence suggests that the gut microbiota plays a crucial role in the development and treatment of various cancers. Recent research on the urinary microbiota challenges the long-standing belief that urine is sterile, as urinary microbiota has been implicated in the development of bladder and prostate cancers, similar to the role of gut microbiota in cancer development. Although the precise involvement of microbiota in the proliferation and differentiation of renal cell carcinoma (RCC) remains unclear, dysbiosis is considered one possible mechanism by which microbiota may contribute to RCC development and treatment. This review summarizes potential mechanisms by which gut microbiota may contribute to the development of RCC, and provides evidence for the involvement of urinary microbiota in RCC. We also explore the role of gut microbiota in RCC treatment and propose that the composition of gut microbiota could serve as a predictive marker for the potential efficacy of immune checkpoint inhibitors (ICIs) in RCC patients. Additionally, evidence suggests that modulating the abundance and distribution of microbiota can enhance the therapeutic effects of drugs, suggesting that microbiota may serve as a promising adjuvant therapy for RCC. Overall, we believe that further investigation into the gut and urinary microbiome of RCC patients could yield valuable insights and strategies for the prevention and personalized treatment of RCC.}, }
@article {pmid37440825, year = {2023}, author = {Pei, B and Ma, X and Wu, N and Wang, C and Yang, W}, title = {Effect of microbiome group on immune checkpoint inhibitors in treatment of gastrointestinal tumors.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {35}, number = {3}, pages = {252-265}, pmid = {37440825}, issn = {1000-9604}, abstract = {In recent years, immune checkpoint blockade (ICB) therapy has become an important treatment strategy for gastrointestinal tumors, however, it only benefits about 1/3 of patients. Since the microbiome has been shown to play an important role in the human body for a long time, a growing number of studies are focusing on its relationship to ICB therapy in cancer, specifically how intestinal microbes affect the efficacy of immune checkpoint inhibitors (ICIs) therapy in patients. On this basis, probiotic interventions, fecal microbiota transplantation (FMT), dietary interventions, and other methods which improve or maintain the structure of the intestinal flora have attracted widespread attention. This article discusses the four aspects of the microbiome, ICB, combined treatment of gastrointestinal tumors, and regulation of gut microbiome. Particularly, the discussion focuses on the contribution of probiotic intervention in improving the therapeutic effect of ICIs to prolong the survival time of patients and reduce the severity of immune-related adverse effects (irAEs).}, }
@article {pmid37440367, year = {2023}, author = {Muralitharan, RR and Snelson, M and Meric, G and Coughlan, MT and Marques, FZ}, title = {Guidelines for microbiome studies in renal physiology.}, journal = {American journal of physiology. Renal physiology}, volume = {325}, number = {3}, pages = {F345-F362}, doi = {10.1152/ajprenal.00072.2023}, pmid = {37440367}, issn = {1522-1466}, mesh = {Animals ; Male ; Female ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents ; }, abstract = {Gut microbiome research has increased dramatically in the last decade, including in renal health and disease. The field is moving from experiments showing mere association to causation using both forward and reverse microbiome approaches, leveraging tools such as germ-free animals, treatment with antibiotics, and fecal microbiota transplantations. However, we are still seeing a gap between discovery and translation that needs to be addressed, so that patients can benefit from microbiome-based therapies. In this guideline paper, we discuss the key considerations that affect the gut microbiome of animals and clinical studies assessing renal function, many of which are often overlooked, resulting in false-positive results. For animal studies, these include suppliers, acclimatization, baseline microbiota and its normalization, littermates and cohort/cage effects, diet, sex differences, age, circadian differences, antibiotics and sweeteners, and models used. Clinical studies have some unique considerations, which include sampling, gut transit time, dietary records, medication, and renal phenotypes. We provide best-practice guidance on sampling, storage, DNA extraction, and methods for microbial DNA sequencing (both 16S rRNA and shotgun metagenome). Finally, we discuss follow-up analyses, including tools available, metrics, and their interpretation, and the key challenges ahead in the microbiome field. By standardizing study designs, methods, and reporting, we will accelerate the findings from discovery to translation and result in new microbiome-based therapies that may improve renal health.}, }
@article {pmid37439281, year = {2023}, author = {Mo, X and Shen, L and Cheng, R and Wang, P and Wen, L and Sun, Y and Wang, Q and Chen, J and Lin, S and Liao, Y and Yang, W and Yan, H and Liu, L}, title = {Faecal microbiota transplantation from young rats attenuates age-related sarcopenia revealed by multiomics analysis.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {14}, number = {5}, pages = {2168-2183}, pmid = {37439281}, issn = {2190-6009}, support = {82230112//National Natural Science Foundation of China/ ; AF2019001-3//Angel Nutrition Research Fund/ ; }, abstract = {BACKGROUND: Gut microbiota plays a key role in the development of sarcopenia via the 'gut-muscle' axis, and probiotics-based therapy might be a strategy for sarcopenia. Fecal microbiota transplantation from young donors (yFMT) has attracted much attention because of its probiotic function. However, whether or not yFMT is effective for sarcopenia in old recipients is largely unknown. Thus, we aimed to investigate the effect and mechanism of yFMT on age-related sarcopenia.<br><br>METHODS: The fecal microbiota of either young (12&#xa0;weeks) or old (88&#xa0;weeks) donor rats was transplanted into aged recipient rats for 8&#xa0;weeks. Then, muscle mass, muscle strength, muscle function, muscle atrophy, and muscle regeneration capacity were measured. Analysis of fecal 16&#xa0;s rRNA, serum non-targeted metabolomic, gut barrier integrity, and muscle transcriptome was conducted to elucidate the interaction between gut microbiota and skeletal muscles.<br><br>RESULTS: As evaluated by magnetic resonance imaging examination, grip strength test (P&#xa0;<&#xa0;0.01), rotarod test (P&#xa0;<&#xa0;0.05), and exhaustive running test (P&#xa0;<&#xa0;0.05), we found that yFMT mitigated muscle mass loss, muscle strength weakness, and muscle function impairment in aged rats. yFMT also countered age-related atrophy and poor regeneration capacity in fast- and slow-switch muscles, which were manifested by the decrease in slow-switch myofibres (both P&#xa0;<&#xa0;0.01) and muscle interstitial fibrosis (both P&#xa0;<&#xa0;0.05) and the increase in the cross-section area of myofibres (both P&#xa0;<&#xa0;0.001), fast-switch myofibres (both P&#xa0;<&#xa0;0.01), and muscle satellite cells (both P&#xa0;<&#xa0;0.001). In addition, yFMT ameliorated age-related dysbiosis of gut microbiota and metabolites by promoting the production of beneficial bacteria and metabolites-Akkermansia, Lactococcus, Lactobacillus, &#x3b3;-glutamyltyrosine, 3R-hydroxy-butanoic acid, and methoxyacetic acid and inhibiting the production of deleterious bacteria and metabolites-Family_XIII_AD3011_group, Collinsella, indoxyl sulfate, indole-3-carboxilic acid-O-sulphate, and trimethylamine N-oxide. Also, yFMT prevented age-related destruction of gut barrier integrity by increasing the density of goblet cells (P&#xa0;<&#xa0;0.0001) and the expression levels of mucin-2 (P&#xa0;<&#xa0;0.0001) and tight junctional proteins (all P&#xa0;<&#xa0;0.05). Meanwhile, yFMT attenuated age-related impairment of mitochondrial biogenesis and function in fast- and slow-switch muscles. Correlation analysis revealed that yFMT-induced alterations of gut microbiota and metabolites might be closely related to mitochondria-related genes and sarcopenia-related phenotypes.<br><br>CONCLUSIONS: yFMT could reshape the dysbiosis of gut microbiota and metabolites, maintain gut barrier integrity, and improve muscle mitochondrial dysfunction, eventually alleviating sarcopenia in aged rats. yFMT might be a new therapeutic strategy for age-related sarcopenia.}, }
@article {pmid37439168, year = {2023}, author = {Fan, J and Sun, Y and Liang, B and Zhang, X and Xiao, C and Huang, Z}, title = {[Role of gut microbiota in perioperative neurocognitive disorders after cardiopulmonary bypass surgery in rats with humanized gut flora].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {43}, number = {6}, pages = {964-969}, pmid = {37439168}, issn = {1673-4254}, mesh = {Male ; Animals ; Rats ; Rats, Sprague-Dawley ; *Cardiopulmonary Bypass ; *Gastrointestinal Microbiome ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Neurocognitive Disorders ; }, abstract = {OBJECTIVE: To investigate whether gut microbiota disturbance after cardiopulmonary bypass (CPB) contributes to the development of perioperative neurocognitive disorders (PND).<br><br>METHODS: Fecal samples were collected from healthy individuals and patients with PND after CPB to prepare suspensions of fecal bacteria, which were transplanted into the colorectum of two groups of pseudo-germ-free adult male SD rats (group NP and group P, respectively), with the rats without transplantation as the control group (n=10). The feces of the rats were collected for macrogenomic sequencing analysis, and serum levels of IL-1&#x3b2;, IL-6 and TNF-&#x3b1; were measured with ELISA. The expression levels of GFAP and p-Tau protein in the hippocampus of the rats were detected using Western blotting, and the cognitive function changes of the rats were assessed with Morris water maze test.<br><br>RESULTS: In all the 3 groups, macrogenomic sequencing analysis showed clustering and clear partitions of the gut microbiota after the transplantation. The relative abundances of Klebsiella in the control group (P < 0.005), Akkermansia in group P (P < 0.005) and Bacteroides in group NP (P < 0.005) were significantly increased after the transplantation. Compared with those in the control group, the rats in group NP and group P showed significantly decreased serum levels of IL-1&#x3b2;, IL-6 and TNF-&#x3b1; and lowered expression levels of GFAP and p-Tau proteins (all P < 0.05). Escape platform crossings and swimming duration in the interest quadrant increased significantly in group NP (P < 0.05), but the increase was not statistically significant in group N. Compared with those in group P, the rats in group NP had significantly lower serum levels of IL-1&#x3b2;, IL-6 and TNF-&#x3b1; and protein expressions of GFAP and p-Tau (all P < 0.05) with better performance in water maze test (P < 0.05).<br><br>CONCLUSION: In patients receiving CPB, disturbances in gut mirobiota contributes to the development of PND possibly in relation with inflammatory response.}, }
@article {pmid37433041, year = {2023}, author = {Wu, H and Leng, X and Liu, Q and Mao, T and Jiang, T and Liu, Y and Li, F and Cao, C and Fan, J and Chen, L and Chen, Y and Yao, Q and Lu, S and Liang, R and Hu, L and Liu, M and Wan, Y and Li, Z and Peng, J and Luo, Q and Zhou, H and Yin, J and Xu, K and Lan, M and Peng, X and Lan, H and Li, G and Han, Y and Zhang, X and Xiao, ZJ and Lang, J and Wang, G and Xu, C}, title = {Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma.}, journal = {Cancer research}, volume = {83}, number = {18}, pages = {3131-3144}, doi = {10.1158/0008-5472.CAN-22-2593}, pmid = {37433041}, issn = {1538-7445}, mesh = {Animals ; Mice ; *Esophageal Squamous Cell Carcinoma/therapy/pathology ; *Esophageal Neoplasms/therapy ; CD8-Positive T-Lymphocytes ; *Microbiota ; Immunotherapy ; Tumor Microenvironment ; }, abstract = {UNLABELLED: Neoadjuvant chemoimmunotherapy (NACI) has shown promise in the treatment of resectable esophageal squamous cell carcinoma (ESCC). The microbiomes of patients can impact therapy response, and previous studies have demonstrated that intestinal microbiota influences cancer immunotherapy by activating gut immunity. Here, we investigated the effects of intratumoral microbiota on the response of patients with ESCC to NACI. Intratumoral microbiota signatures of β-diversity were disparate and predicted the treatment efficiency of NACI. The enrichment of Streptococcus positively correlated with GrzB+ and CD8+ T-cell infiltration in tumor tissues. The abundance of Streptococcus could predict prolonged disease-free survival in ESCC. Single-cell RNA sequencing demonstrated that responders displayed a higher proportion of CD8+ effector memory T cells but a lower proportion of CD4+ regulatory T cells. Mice that underwent fecal microbial transplantation or intestinal colonization with Streptococcus from responders showed enrichment of Streptococcus in tumor tissues, elevated tumor-infiltrating CD8+ T cells, and a favorable response to anti-PD-1 treatment. Collectively, this study suggests that intratumoral Streptococcus signatures could predict NACI response and sheds light on the potential clinical utility of intratumoral microbiota for cancer immunotherapy.<br><br>SIGNIFICANCE: Analysis of intratumoral microbiota in patients with esophageal cancer identifies a microbiota signature that is associated with chemoimmunotherapy response and reveals that Streptococcus induces a favorable response by stimulating CD8+ T-cell infiltration. See related commentary by Sfanos, p. 2985.}, }
@article {pmid37432606, year = {2023}, author = {Feitelson, MA and Arzumanyan, A and Medhat, A and Spector, I}, title = {Short-chain fatty acids in cancer pathogenesis.}, journal = {Cancer metastasis reviews}, volume = {42}, number = {3}, pages = {677-698}, pmid = {37432606}, issn = {1573-7233}, mesh = {Humans ; *Dysbiosis ; Cytokines/metabolism ; Inflammation/metabolism ; *Neoplasms/etiology ; Fatty Acids, Volatile/metabolism ; }, abstract = {Cancer is a multi-step process that can be viewed as a cellular and immunological shift away from homeostasis in response to selected infectious agents, mutations, diet, and environmental carcinogens. Homeostasis, which contributes importantly to the definition of "health," is maintained, in part by the production of short-chain fatty acids (SCFAs), which are metabolites of specific gut bacteria. Alteration in the composition of gut bacteria, or dysbiosis, is often a major risk factor for some two dozen tumor types. Dysbiosis is often characterized by diminished levels of SCFAs in the stool, and the presence of a "leaky gut," permitting the penetration of microbes and microbial derived molecules (e.g., lipopolysaccharides) through the gut wall, thereby triggering chronic inflammation. SCFAs attenuate inflammation by inhibiting the activation of nuclear factor kappa B, by decreasing the expression of pro-inflammatory cytokines such as tumor necrosis factor alpha, by stimulating the expression of anti-inflammatory cytokines such as interleukin-10 and transforming growth factor beta, and by promoting the differentiation of naïve T cells into T regulatory cells, which down-regulate immune responses by immunomodulation. SCFA function epigenetically by inhibiting selected histone acetyltransferases that alter the expression of multiple genes and the activity of many signaling pathways (e.g., Wnt, Hedgehog, Hippo, and Notch) that contribute to the pathogenesis of cancer. SCFAs block cancer stem cell proliferation, thereby potentially delaying or inhibiting cancer development or relapse by targeting genes and pathways that are mutated in tumors (e.g., epidermal growth factor receptor, hepatocyte growth factor, and MET) and by promoting the expression of tumor suppressors (e.g., by up-regulating PTEN and p53). When administered properly, SCFAs have many advantages compared to probiotic bacteria and fecal transplants. In carcinogenesis, SCFAs are toxic against tumor cells but not to surrounding tissue due to differences in their metabolic fate. Multiple hallmarks of cancer are also targets of SCFAs. These data suggest that SCFAs may re-establish homeostasis without overt toxicity and either delay or prevent the development of various tumor types.}, }
@article {pmid37431863, year = {2023}, author = {Han, B and Lv, X and Liu, G and Li, S and Fan, J and Chen, L and Huang, Z and Lin, G and Xu, X and Huang, Z and Zhan, L and Lv, X}, title = {Gut microbiota-related bile acid metabolism-FXR/TGR5 axis impacts the response to anti-α4β7-integrin therapy in humanized mice with colitis.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2232143}, pmid = {37431863}, issn = {1949-0984}, mesh = {Animals ; Mice ; Humans ; *Gastrointestinal Microbiome ; Caco-2 Cells ; *Colitis/chemically induced/drug therapy ; *Inflammatory Bowel Diseases ; Bile Acids and Salts ; Integrins ; }, abstract = {The gut microbiota and bile acid metabolism are key determinants of the response of inflammatory bowel disease to biologic therapy. However, the molecular mechanisms underlying the interactions between the response to anti-α4β7-integrin therapy and the gut microbiota and bile acid metabolism remain unknown. In this research, we investigated the role of gut microbiota-related bile acid metabolism on the response to anti-α4β7-integrin therapy in a humanized immune system mouse model with colitis induced by 2,4,6-trinitrobenzene sulfonic acid. We found that anti-α4β7-integrin significantly mitigated intestinal inflammation, pathological symptoms, and gut barrier disruption in remission-achieving colitis mice. Whole-genome shotgun metagenomic sequencing demonstrated that employing baseline microbiome profiles to predict remission and the treatment response was a promising strategy. Antibiotic-mediated gut microbiota depletion and fecal microbiome transplantation revealed that the baseline gut microbiota contained common microbes with anti-inflammatory effects and reduced mucosal barrier damage, improving the treatment response. Targeted metabolomics analysis illustrated that bile acids associated with microbial diversity were involved in colitis remission. Furthermore, the activation effects of the microbiome and bile acids on FXR and TGR5 were evaluated in colitis mice and Caco-2 cells. The findings revealed that the production of gastrointestinal bile acids, particularly CDCA and LCA, further directly promoted the stimulation of FXR and TGR5, significantly improving gut barrier function and suppressing the inflammatory process. Taken together, gut microbiota-related bile acid metabolism-FXR/TGR5 axis may be a potential mechanism for impacting the response to anti-α4β7-integrin in experimental colitis. Thus, our research provides novel insights into the treatment response in inflammatory bowel disease.}, }
@article {pmid37431860, year = {2023}, author = {Jain, N and Umar, TP and Fahner, AF and Gibietis, V}, title = {Advancing therapeutics for recurrent clostridioides difficile infections: an overview of vowst's FDA approval and implications.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2232137}, pmid = {37431860}, issn = {1949-0984}, mesh = {United States ; Humans ; *Clostridioides difficile ; *Gastrointestinal Microbiome ; United States Food and Drug Administration ; *Clostridium Infections/drug therapy/prevention &amp; control ; *Cross Infection ; }, abstract = {Clostridioides difficile infections (CDI) are a leading cause of healthcare-associated infections with a high relapse rate. Current treatment guidelines recommend fidaxomicin as the primary therapy for initial CDI episodes and suggest alternative approaches for recurrent episodes, including fecal microbiota transplantation (FMT). This paper explores the recent approval of Vowst, a novel oral FMT drug, by the United States Food and Drug Administration (FDA) as a prophylactic therapy to prevent recurrent CDIs. Vowst comprises a formulation of live fecal microbiota spores and works by reestablishing the disrupted gut microbiota, limiting C. difficile spore germination, and promoting microbiome repair. Furthermore, this paper will discuss the product's approval journey and the uncertainties regarding its efficacy in CDI patients beyond the ones who participated in the clinical trials, pharmacovigilance, cost estimates, and the need for a more stringent donor screening process. Overall, Vowst's approval marks a significant step forward in the prevention of recurrent CDI infections with various beneficial implications for future gastroenterology.}, }
@article {pmid37431096, year = {2023}, author = {Kim, HM and Lee, J and Kim, S and Lee, JW and Kim, HJ and Cho, YS}, title = {Fecal microbiota transplantation for steroid-refractory gastrointestinal graft-versus-host disease.}, journal = {Blood research}, volume = {58}, number = {3}, pages = {145-148}, pmid = {37431096}, issn = {2287-979X}, }
@article {pmid37429676, year = {2023}, author = {Wilson, BC and Derraik, JGB and Albert, BB and Leong, KSW and Tweedie-Cullen, RY and Creagh, C and Depczynski, M and Edwards, T and Vatanen, T and Thabrew, H and Cutfield, WS and O'Sullivan, JM}, title = {An open-label pilot trial of faecal microbiome transfer to restore the gut microbiome in anorexia nervosa: protocol.}, journal = {BMJ open}, volume = {13}, number = {7}, pages = {e070616}, pmid = {37429676}, issn = {2044-6055}, mesh = {Female ; *Anorexia Nervosa/therapy ; Capsules ; *Gastrointestinal Microbiome ; *Microbiota ; Pilot Projects ; Humans ; Adolescent ; Young Adult ; Adult ; }, abstract = {INTRODUCTION: Individuals with anorexia nervosa (AN) harbour distinct gut microbiomes compared with healthy individuals, which are sufficient to induce weight loss and anxiety-like behaviours when transplanted into germ-free mice. We hypothesise that faecal microbiome transfer (FMT) from healthy donors would help restore the gut microbiome of individuals with AN, which in turn, may aid patient recovery.<br><br>METHODS: We aim to conduct an open-label pilot study in 20 females aged 16-32 years in Auckland, New Zealand who meet the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria for AN and have a body mass index 13-19&#x2009;kg/m[2]. We will recruit four healthy, lean, female donors, aged 18-32 years, who will undergo extensive clinical screening prior to stool donation. Faecal microbiota will be harvested from donors and double encapsulated in delayed release, acid-resistant capsules. All participants will receive a single course of 20 FMT capsules (five from each donor) which they can choose to take over two or four consecutive days. Stool and blood samples will be collected from participants over a period of 3&#x2009;months to assess their gut microbiome profile, metabolome, levels of intestinal inflammation and nutritional status. Our primary outcome is a shift in the gut microbiome composition at 3 weeks post-FMT (Bray-Curtis dissimilarity). We will also monitor participants' body composition (whole-body dual-energy X-ray absorptiometry scans), eating disorder psychopathology, mental health and assess their views on, and tolerability of, treatment. All adverse events will be recorded and reviewed by an independent data monitoring committee.<br><br>ETHICS AND DISSEMINATION: Ethics approval was provided by the Central Health and Disability Ethics Committee (Ministry of Health, New Zealand, 21/CEN/212). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12621001504808.}, }
@article {pmid37429503, year = {2024}, author = {Wei, J and Zheng, Z and Hou, X and Jia, F and Yuan, Y and Yuan, F and He, F and Hu, L and Zhao, L}, title = {Echinacoside inhibits colorectal cancer metastasis via modulating the gut microbiota and suppressing the PI3K/AKT signaling pathway.}, journal = {Journal of ethnopharmacology}, volume = {318}, number = {Pt A}, pages = {116866}, doi = {10.1016/j.jep.2023.116866}, pmid = {37429503}, issn = {1872-7573}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; RNA, Ribosomal, 16S ; Signal Transduction ; Fatty Acids, Volatile/metabolism ; Butyrates/therapeutic use ; *Colonic Neoplasms/pathology ; Glycosides/pharmacology/therapeutic use ; *Liver Neoplasms/drug therapy ; Disease Models, Animal ; *Colorectal Neoplasms/drug therapy/metabolism ; }, abstract = {Echinacoside (ECH) is the dominant phenylethanoid glycoside-structured compound identified from our developed herbal formula Huangci granule, which has been previously reported to inhibit the invasion and metastasis of CRC and prolong patients' disease-free survival duration. Though ECH has inhibitory activity against aggressive colorectal cancer (CRC) cells, its anti-metastasis effect in vivo and the action mechanism is undetermined. Given that ECH has an extremely low bioavailability and gut microbiota drives the CRC progression, we hypothesized that ECH could inhibit metastatic CRC by targeting the gut microbiome.<br><br>AIM OF THE STUDY: The purpose of this study was to investigate the impact of ECH on colorectal cancer liver metastasis in vivo and its potential mechanisms.<br><br>MATERIALS AND METHODS: An intrasplenic injection-induced liver metastatic model was established to examine the efficiency of ECH on tumor metastasis in vivo. Fecal microbiota from the model group and the ECH group were separately transplanted into pseudo-sterile CRLM mice in order to verify the role of gut flora in the ECH anti-metastatic effect. The 16S rRNA gene sequence was applied to analyze the structure and composition of the gut microbiota after ECH intervention, and the effect of ECH on short-chain fatty acid (SCFAs)-producing bacteria growth was proven by anaerobic culturing in vitro. GC-MS was applied to quantitatively analyze the serum SCFAs levels in mice. RNA-seq was performed to detect the gene changes involving tumor-promoting signaling pathway.<br><br>RESULTS: ECH inhibited CRC metastasis in a dose-dependent manner in the metastatic colorectal cancer (mCRC) mouse model. Manipulation of gut bacteria in the mCRC mouse model further proved that SCFA-generating gut bacteria played an indispensable role in mediating the antimetastatic action of ECH. Under an anaerobic condition, ECH benefited SCFA-producing microbiota without affecting the total bacterial load, presenting a dose-dependent promotion on the growth of a butyrate producer, Faecalibacterium prausnitzii (F.p). Furthermore, ECH-reshaped or F.p-colonized microbiota with a high butyrate-producing capability inhibited liver metastasis by suppressing PI3K/AKT signaling and reversing the epithelial-mesenchymal transition (EMT) process, whereas this anti-metastatic ability was abrogated by the butyrate synthase inhibitor heptanoyl-CoA.<br><br>CONCLUSION: This study demonstrated that ECH exhibits oral anti-metastatic efficacy by facilitating butyrate-producing gut bacteria, which downregulates PI3K/AKT signaling and EMT. It hints at a novel role for ECH in CRC therapy.}, }
@article {pmid37429232, year = {2023}, author = {Song, W and Yue, Y and Zhang, Q}, title = {Imbalance of gut microbiota is involved in the development of chronic obstructive pulmonary disease: A review.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {165}, number = {}, pages = {115150}, doi = {10.1016/j.biopha.2023.115150}, pmid = {37429232}, issn = {1950-6007}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Pulmonary Disease, Chronic Obstructive ; Lung ; *Lung Diseases ; Inflammation ; }, abstract = {Chronic obstructive pulmonary disease (COPD) is a common chronic disease characterized by chronic airway inflammation and remodeling, which seriously endangers human health. Recent developments in genomics and metabolomics have revealed the roles of the gut microbiota and its metabolites in COPD. Dysbiosis of the gut microbiota directly increases gut permeability, thereby promoting the translocation of pathological bacteria. The gut microbiota and associated metabolites may influence the development and progression of COPD by modulating immunity and inflammation. Furthermore, the systemic hypoxia and oxidative stress that occur in COPD may also be involved in intestinal dysfunction. The cross-talk between the gut and lungs is known as the gut-lung axis; however, an overview of its mechanism is lacking. This review highlights the critical and complex interplay of gut microbiota and immune responses in the gut-lung axis, further explores possible links between the gut and lungs, and summarizes new interventions through diet, probiotics, vitamins, and fecal microbiota transplantation, which are critical to COPD.}, }
@article {pmid37427566, year = {2024}, author = {El-Salhy, M and Gilja, OH and Hatlebakk, JG}, title = {Factors affecting the outcome of fecal microbiota transplantation for patients with irritable bowel syndrome.}, journal = {Neurogastroenterology and motility}, volume = {36}, number = {1}, pages = {e14641}, doi = {10.1111/nmo.14641}, pmid = {37427566}, issn = {1365-2982}, support = {//Hesle Fonna/ ; }, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Irritable Bowel Syndrome/diagnosis ; Quality of Life ; RNA, Ribosomal, 16S ; Treatment Outcome ; *Gastrointestinal Microbiome/physiology ; Feces/microbiology ; Dysbiosis/microbiology ; Bacteria ; }, abstract = {BACKGROUND: A previous study that introduced a Fecal microbiota transplantation (FMT) protocol with a high efficacy applied a combination of favorable factors.<br><br>AIMS: The present study aimed to evaluate some of these factors.<br><br>METHODS: This study included 186 patients with IBS randomized 1:1:1 into transplant administered to the colon (single LI), to the duodenum (single SI), or to the duodenum twice with a 1-week interval (repeated SI). The patients provided a fecal sample and were asked to complete five questionnaires at baseline and at 3, 6, and 12&#x2009;months after FMT. The fecal bacteria composition and dysbiosis index (DI) were analyzed using 16S rRNA gene PCR DNA amplification/probe hybridization covering regions V3-V9.<br><br>RESULTS: The response rate was significantly higher in single SI than in single LI at 12&#x2009;months after FMT. Symptoms and quality of life improved in all the treated groups at all time intervals after FMT. The abdominal symptoms were significantly reduced and the quality of life improved for repeated SI compared with for single SI. DI significantly decreased in all the treated groups at all observation times after FMT. The bacterial profiles changed in all groups at all observation intervals. However, these changes differed between single LI and single SI/repeated SI.<br><br>CONCLUSION: Administrating transplant to the small intestine had a long-term higher response rate than that administrated to the large intestine, and led to long-term colonization of beneficial bacteria. Repeating FMT had more effect on symptoms and quality of life than a single FMT. (www.<br><br>CLINICALTRIALS: gov: NCT04236843).}, }
@article {pmid37424343, year = {2023}, author = {Yan, Q and Su, S and Dai, G and He, L}, title = {Prebiotics Modulate Gut Microbiota-mediated T-cell Immunity to Enhance the Inhibitory Effect of Sintilimab in Lewis Lung Adenocarcinoma Model Mice.}, journal = {Anti-cancer agents in medicinal chemistry}, volume = {23}, number = {17}, pages = {1966-1973}, doi = {10.2174/1871520623666230707112244}, pmid = {37424343}, issn = {1875-5992}, abstract = {BACKGROUND: Sintilimab (Sin) helps the body to restore the anti-tumor response of T lymphocytes. However, in clinical use, the treatment process is more complicated due to adverse effects and different dosing regimens. It is not clear whether prebiotics (PREB) have a potentiating effect on Sin for lung adenocarcinoma, and this study intends to investigate the inhibitory effect, safety and possible mechanism of Sin combined with PREB on lung adenocarcinoma from animal experiments.<br><br>METHODS: Lewis lung adenocarcinoma cells were inoculated into the right axilla of mice subcutaneously to prepare the Lewis lung cancer mouse model and treated in groups. The volume of transplanted tumors was measured, the histopathology of the liver and kidney of mice was observed by H&amp;E staining, the levels of ALT, AST, UREA, CREA, WBC, RBC, and HGB in blood were analyzed biochemically; the ratio of T-cell subpopulations in blood, spleen, and bone marrow was detected by flow cytometry, the expression of PD-L1 in tumor tissue was detected by immunofluorescence staining, and 16S rRNA to analyze the diversity of fecal flora.<br><br>RESULTS: Sin inhibited tumor growth and regulated immune cell homeostasis in lung adenocarcinoma mice, but liver and kidney histopathology showed different degrees of damage after Sin treatment, while the addition of PREB reduced liver and kidney damage in lung adenocarcinoma mice and promoted Sin's regulation of immune cells. In addition, the beneficial effects of Sin were associated with changes in intestinal flora diversity.<br><br>CONCLUSION: The mechanism by which Sintilimab combined with prebiotics inhibits tumor volume and regulates immune cell subpopulation balance in lung adenocarcinoma mice may be related to gut microbes.}, }
@article {pmid37423726, year = {2023}, author = {Yoshimatsu, Y and Sujino, T and Kanai, T}, title = {[Involvement of microbiota in IBD and bacteriotherapy].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {120}, number = {7}, pages = {554-561}, doi = {10.11405/nisshoshi.120.554}, pmid = {37423726}, issn = {0446-6586}, mesh = {Humans ; *Microbiota ; Fecal Microbiota Transplantation ; *Inflammatory Bowel Diseases/therapy ; }, }
@article {pmid37422760, year = {2023}, author = {Lai, Y and Wu, X and Chao, E and Bloomstein, JD and Wei, G and Hwang, ST and Shi, Z}, title = {Impact of Gut Bacterial Metabolites on Psoriasis and Psoriatic Arthritis: Current Status and Future Perspectives.}, journal = {The Journal of investigative dermatology}, volume = {143}, number = {9}, pages = {1657-1666}, doi = {10.1016/j.jid.2023.05.012}, pmid = {37422760}, issn = {1523-1747}, mesh = {Humans ; *Arthritis, Psoriatic ; *Gastrointestinal Microbiome ; *Psoriasis/therapy/microbiology ; Fecal Microbiota Transplantation ; Dysbiosis/microbiology ; }, abstract = {There is growing evidence that supports a role of gut dysbiosis in the pathogenesis of psoriasis (Pso). Thus, probiotic supplementation and fecal microbiota transplantation may serve as promising preventive and therapeutic strategies for patients with Pso. One of the basic mechanisms through which the gut microbiota interacts with the host is through bacteria-derived metabolites, usually intermediate or end products produced by microbial metabolism. In this study, we provide an up-to-date review of the most recent literature on microbial-derived metabolites and highlight their roles in the immune system, with a special focus on Pso and one of its most common comorbidities, psoriatic arthritis.}, }
@article {pmid37422682, year = {2023}, author = {Shang, H and Huang, C and Xiao, Z and Yang, P and Zhang, S and Hou, X and Zhang, L}, title = {Gut microbiota-derived tryptophan metabolites alleviate liver injury via AhR/Nrf2 activation in pyrrolizidine alkaloids-induced sinusoidal obstruction syndrome.}, journal = {Cell &amp; bioscience}, volume = {13}, number = {1}, pages = {127}, pmid = {37422682}, issn = {2045-3701}, support = {81800463//National Natural Science Foundation of China/ ; 81720108006//National Natural Science Foundation of China/ ; 81570486//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND AND AIMS: Hepatic sinusoidal obstruction syndrome (HSOS) is caused by toxic injury, such as pyrrolizidine alkaloids, to the liver sinusoidal endothelial cells, and the gut microbiota may be involved. However, the specific role and underlying mechanism of gut microbiota in HSOS is unknown.<br><br>METHODS: HSOS model was established by gavage of monocrotaline (MCT) in rats. Fecal microbiota transplantation (FMT) with HSOS-derived or healthy gut flora was also conducted to validate the role of gut microflora in MCT-induced liver injury. The microbial 16&#xa0;s rRNA analysis and untargeted metabolomics analysis in the faeces were performed to identify HSOS-related flora and metabolites. Finally, by supplementation with specific tryptophan metabolites, such as indole-3-acetaldehyde (IAAld) and indole acetic acid (IAA), we further confirmed the role of tryptophan metabolism in HSOS and the role of the AhR/Nrf2 pathway in MCT-induced liver injury.<br><br>RESULTS: MCT induced HSOS-like liver injury in rats with significantly altered gut microbiota. Particularly, some tryptophan-metabolizing bacteria reduced in MCT-treated rats, such as Bacteroides, Bifidobacterium, Lactobacillus and Clostridium, and accompanied by a decrease in microbial tryptophan metabolic activity and a series of tryptophan derivatives. Restoring the gut microbiota via FMT improved MCT-induced liver damage, while HSOS-derived gut microbiota aggravated the liver injury induced by MCT. Supplementation with microbial tryptophan derivatives (IAAld or IAA), or 6-formylindolo(3,2-b)carbazole (Ficz, an AhR agonist) could activate the AhR/Nrf2 signaling pathway, thereby attenuating the MCT-induced liver oxidative stress and liver sinusoidal endothelial cells injury.<br><br>CONCLUSIONS: Gut microbiota plays a critical role in MCT-induced HSOS, with inadequate microbial tryptophan metabolism in the gut and consequently a lower activity of the AhR/Nrf2 signaling pathway in the liver, which should be a potential target for the management of HSOS.}, }
@article {pmid37422372, year = {2023}, author = {Jiang, ZM and Zeng, SL and Huang, TQ and Lin, Y and Wang, FF and Gao, XJ and Li, J and Li, P and Liu, EH}, title = {Sinomenine ameliorates rheumatoid arthritis by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation.}, journal = {Science bulletin}, volume = {68}, number = {14}, pages = {1540-1555}, doi = {10.1016/j.scib.2023.06.027}, pmid = {37422372}, issn = {2095-9281}, abstract = {Gut microbiota dysbiosis is associated with the development of rheumatoid arthritis (RA). Sinomenine (SIN) is an effective immunosuppressive and anti-inflammatory drug used for treating RA, but how SIN regulates gut microbiota to alleviate RA remains underexplored. To identify the critical gut microbial species and microbial metabolites associated with the RA-protective effects of SIN, the microbiota-dependent anti-RA effects of SIN were assessed by 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation. Metabolomics analysis, transcriptional analysis, and targeted bacteria/metabolites gavage were conducted to explore how SIN regulates gut microbiota to reduce the severity of RA. SIN could restore intestinal microbial balance by mainly modulating the abundance of Lactobacillus, and significantly relieve collagen-induced arthritis (CIA) symptoms in a gut microbiota-dependent manner. SIN significantly elevated microbial tryptophan metabolites indole-3-acrylic acid (IA), indole-3-propionic acid (IPA), and indole-3-acetic acid (IAA). Tryptophan metabolites supplementation could activate aryl hydrocarbon receptor (AhR) and regulate Th17/Treg balance in CIA rats. Intriguingly, SIN relieved the arthritis symptoms involving the enrichment of two beneficial anti-CIA Lactobacillus species, L. paracasei and L. casei by mono-colonization. The promising therapeutic function of SIN was mostly attributed to the activation of AhR by explicitly targeting the Lactobacillus and microbial tryptophan metabolites. The intestinal bacterium L. paracasei and L. casei may be used to reduce the severity of CIA.}, }
@article {pmid37422196, year = {2023}, author = {Wong, SP and Er, YX and Tan, SM and Lee, SC and Rajasuriar, R and Lim, YAL}, title = {Oral and Gut Microbiota Dysbiosis is Associated with Mucositis Severity in Autologous Hematopoietic Stem Cell Transplantation: Evidence from an Asian Population.}, journal = {Transplantation and cellular therapy}, volume = {29}, number = {10}, pages = {633.e1-633.e13}, doi = {10.1016/j.jtct.2023.06.016}, pmid = {37422196}, issn = {2666-6367}, abstract = {Mucositis is a debilitating complication of hematopoietic stem cell transplantation (HSCT). It is unclear how changes in the composition of microbiota, which are modulated by geographical location and ethnicity, may influence immune regulation leading to the development of mucositis, and the study of both oral and gut microbiota in a single population of autologous HSCT in the Asian region is lacking. The present study aimed to characterize the oral and gut microbiota changes, and the impact on both oral and lower gastrointestinal (GI) mucositis, with associated temporal changes in a population of adult recipients of autologous HSCT. Autologous HSCT recipients age ≥18 years were recruited from Hospital Ampang, Malaysia, between April 2019 and December 2020. Mucositis assessments were conducted daily, and blood, saliva, and fecal samples were collected prior to conditioning, on day 0, and at 7 days and 6 months post-transplantation. Longitudinal differences in alpha diversity and beta diversity were determined using the Wilcoxon signed-rank test and permutational multivariate analysis of variance, respectively. Changes in relative abundances of bacteria across time points were assessed using the microbiome multivariate analysis by linear models function. The combined longitudinal effects of clinical, inflammatory, and microbiota variables on mucositis severity were measured using the generalized estimating equation. Among the 96 patients analyzed, oral mucositis and diarrhea (representing lower GI mucositis) occurred in 58.3% and 95.8%, respectively. Alpha and beta diversities were significantly different between sample types (P < .001) and across time points, with alpha diversity reaching statistical significance at day 0 in fecal samples (P < .001) and at day +7 in saliva samples (P < .001). Diversities normalized to baseline by 6 months post-transplantation. Significant microbiota, clinical, and immunologic factors were associated with increasing mucositis grades. Increasing relative abundances of saliva Paludibacter, Leuconostoc, and Proteus were associated with higher oral mucositis grades, whereas increasing relative abundances of fecal Rothia and Parabacteroides were associated with higher GI mucositis grades. Meanwhile, increasing relative abundances of saliva Lactococcus and Acidaminococcus and fecal Bifidobacterium were associated with protective effects against worsening oral and GI mucositis grades, respectively. This study provides real-world evidence and insights into the dysbiosis of the microbiota in patients exposed to conditioning regimen during HSCT. Independent of clinical and immunologic factors, we demonstrated significant associations between relative bacteria abundances with the increasing severity of oral and lower GI mucositis. Our findings offer a potential rationale to consider the inclusion of preventive and restorative measures targeting oral and lower GI dysbiosis as interventional strategies to ameliorate mucositis outcome in HSCT recipients.}, }
@article {pmid37419267, year = {2023}, author = {Zhou, YF and Nie, J and Shi, C and Zheng, WW and Ning, K and Kang, J and Sun, JX and Cong, X and Xie, Q and Xiang, H}, title = {Lysimachia christinae polysaccharide attenuates diet-induced hyperlipidemia via modulating gut microbes-mediated FXR-FGF15 signaling pathway.}, journal = {International journal of biological macromolecules}, volume = {248}, number = {}, pages = {125725}, doi = {10.1016/j.ijbiomac.2023.125725}, pmid = {37419267}, issn = {1879-0003}, mesh = {Mice ; Animals ; Lysimachia ; *Hyperlipidemias/drug therapy/etiology/metabolism ; *Gastrointestinal Microbiome ; Bile Acids and Salts/metabolism ; Polysaccharides/pharmacology/metabolism ; Cholesterol/metabolism ; Diet, High-Fat/adverse effects ; Signal Transduction ; Fibroblast Growth Factors/metabolism ; Mice, Inbred C57BL ; Liver ; }, abstract = {Polysaccharides are one of the most abundant and active components of Lysimachia christinae (L. christinae), which is widely adopted for attenuating abnormal cholesterol metabolism; however, its mechanism of action remains unclear. Therefore, we fed a natural polysaccharide (NP) purified from L. christinae to high-fat diet mice. These mice showed an altered gut microbiota and bile acid pool, which was characterized by significantly increased Lactobacillus murinus and unconjugated bile acids in the ileum. Oral administration of the NP reduced cholesterol and triglyceride levels and enhanced bile acid synthesis via cholesterol 7α-hydroxylase. Additionally, the effects of NP are microbiota-dependent, which was reconfirmed by fecal microbiota transplantation (FMT). Altered gut microbiota reshaped bile acid metabolism by modulating bile salt hydrolase (BSH) activity. Therefore, bsh genes were genetically engineered into Brevibacillus choshinensis, which was gavaged into mice to verify BSH function in vivo. Finally, adeno-associated-virus-2-mediated overexpression or inhibition of fibroblast growth factor 15 (FGF15) was used to explore the farnesoid X receptor-fibroblast growth factor 15 pathway in hyperlipidemic mice. We identified that the NP relieves hyperlipidemia by altering the gut microbiota, which is accompanied by the active conversion of cholesterol to bile acids.}, }
@article {pmid37416999, year = {2023}, author = {Tang, H and Li, H and Li, D and Peng, J and Zhang, X and Yang, W}, title = {The Gut Microbiota of Pregnant Rats Alleviates Fetal Growth Restriction by Inhibiting the TLR9/MyD88 Pathway.}, journal = {Journal of microbiology and biotechnology}, volume = {33}, number = {9}, pages = {1213-1227}, pmid = {37416999}, issn = {1738-8872}, mesh = {Humans ; Pregnancy ; Female ; Rats ; Animals ; *Myeloid Differentiation Factor 88/genetics/metabolism ; Toll-Like Receptor 9/metabolism ; *Gastrointestinal Microbiome ; Fetal Growth Retardation ; RNA, Ribosomal, 16S/genetics ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Fetal growth restriction (FGR) is a prevalent obstetric condition. This study aimed to investigate the role of Toll-like receptor 9 (TLR9) in regulating the inflammatory response and gut microbiota structure in FGR. An FGR animal model was established in rats, and ODN1668 and hydroxychloroquine (HCQ) were administered. Changes in gut microbiota structure were assessed using 16S rRNA sequencing, and fecal microbiota transplantation (FMT) was conducted. HTR-8/Svneo cells were treated with ODN1668 and HCQ to evaluate cell growth. Histopathological analysis was performed, and relative factor levels were measured. The results showed that FGR rats exhibited elevated levels of TLR9 and myeloid differentiating primary response gene 88 (MyD88). In vitro experiments demonstrated that TLR9 inhibited trophoblast cell proliferation and invasion. TLR9 upregulated lipopolysaccharide (LPS), LPS-binding protein (LBP), interleukin (IL)-1β and tumor necrosis factor (TNF)-α while downregulating IL-10. TLR9 activated the TARF3-TBK1-IRF3 signaling pathway. In vivo experiments showed HCQ reduced inflammation in FGR rats, and the relative cytokine expression followed a similar trend to that observed in vitro. TLR9 stimulated neutrophil activation. HCQ in FGR rats resulted in changes in the abundance of Eubacterium_coprostanoligenes_group at the family level and the abundance of Eubacterium_coprostanoligenes_group and Bacteroides at the genus level. TLR9 and associated inflammatory factors were correlated with Bacteroides, Prevotella, Streptococcus, and Prevotellaceae_Ga6A1_group. FMT from FGR rats interfered with the therapeutic effects of HCQ. In conclusion, our findings suggest that TLR9 regulates the inflammatory response and gut microbiota structure in FGR, providing new insights into the pathogenesis of FGR and suggesting potential therapeutic interventions.}, }
@article {pmid37416062, year = {2023}, author = {Ma, J and Wei, Q and Cheng, X and Zhang, J and Zhang, Z and Su, J}, title = {Potential role of gut microbes in the efficacy and toxicity of immune checkpoints inhibitors.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1170591}, pmid = {37416062}, issn = {1663-9812}, abstract = {In recent years, Immune checkpoint inhibitors have been extensively used in the treatment of a variety of cancers. However, the response rates ranging from 13% to 69% depending on the tumor type and the emergence of immune-related adverse events have posed significant challenges for clinical treatment. As a key environmental factor, gut microbes have a variety of important physiological functions such as regulating intestinal nutrient metabolism, promoting intestinal mucosal renewal, and maintaining intestinal mucosal immune activity. A growing number of studies have revealed that gut microbes further influence the anticancer effects of tumor patients through modulation of the efficacy and toxicity of immune checkpoint inhibitors. Currently, faecal microbiota transplantation (FMT) have been developed relatively mature and suggested as an important regulator in order to enhance the efficacy of treatment. This review is dedicated to exploring the impact of differences in flora composition on the efficacy and toxicity of immune checkpoint inhibitors as well as to summarizing the current progress of FMT.}, }
@article {pmid37415149, year = {2023}, author = {Chandra, S and Di Meco, A and Dodiya, HB and Popovic, J and Cuddy, LK and Weigle, IQ and Zhang, X and Sadleir, K and Sisodia, SS and Vassar, R}, title = {The gut microbiome regulates astrocyte reaction to Aβ amyloidosis through microglial dependent and independent mechanisms.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {45}, pmid = {37415149}, issn = {1750-1326}, support = {F30 AG079577/AG/NIA NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; F30AG079577/AG/NIA NIH HHS/United States ; }, mesh = {Mice ; Male ; Female ; Animals ; Amyloid beta-Peptides/metabolism ; *Alzheimer Disease/metabolism ; Microglia/metabolism ; Astrocytes/metabolism ; Amyloid beta-Protein Precursor/metabolism ; *Gastrointestinal Microbiome ; Mice, Transgenic ; Gliosis/metabolism ; *Amyloidosis/metabolism ; Plaque, Amyloid/pathology ; }, abstract = {BACKGROUND: Previous studies show that antibiotic-mediated (abx) alteration of the gut microbiome (GMB) results in a reduction of amyloid beta (Aβ) plaques and proinflammatory microglial phenotype in male APPPS1-21 mice. However, the effect of GMB perturbation on astrocyte phenotypes and microglial-astrocyte communication in the context of amyloidosis has not been examined.<br><br>METHODS: To study whether the GMB modulates astrocyte phenotype in the context of amyloidosis, APPPS1-21 male and female mice were treated with broad-spectrum abx leading to GMB perturbation. GFAP&#x2009;+&#x2009;astrocytes, plaque-associated astrocytes (PAA), PAA morphological parameters, and astrocyte complement component C3 levels were quantified using a combination of immunohistochemistry, immunoblotting, widefield microscopy, and confocal microscopy. Furthermore, these same astrocyte phenotypes were assessed in abx-treated APPPS1-21 male mice that received either fecal matter transplant (FMT) from untreated APPPS1-21&#xa0;male donors to restore their microbiome or vehicle control. To assess complete absence of the GMB on astrocyte phenotypes, the same astrocyte phenotypes were quantified in APPPS1-21 male mice raised in germ-free (GF) or specific-pathogen free conditions (SPF). Lastly, we assessed whether microglia are necessary for abx-induced astrocyte phenotypes by depleting microglia in APPPS1-21 male mice via treatment with a colony-stimulating factor 1 receptor (CSF1R) inhibitor (PLX5622) and vehicle control or PLX5622 and abx.<br><br>RESULTS: Herein, we demonstrate that postnatal treatment of male APPPS1-21 mice with broad-spectrum abx leading to GMB perturbation reduces GFAP&#x2009;+&#x2009;reactive astrocytes and PAAs, suggesting that the GMB plays a role in regulating reactive astrocyte induction and recruitment to A&#x3b2; plaques. Additionally, we show that compared to controls, PAAs in abx-treated male APPPS1-21 mice exhibit an altered morphology with increased number and length of processes and reduced astrocytic complement C3, consistent with a homeostatic phenotype. GFAP&#x2009;+&#x2009;astrocyte reduction, PAA reduction, astrocyte morphological changes, and C3 levels are restored when abx-treated mice are subject to FMT from untreated APPPS1-21 male donor mice. Next, we found that APPPS1-21 male mice raised in GF conditions have similar astrocyte phenotypes as abx-treated male APPPS1-21 male mice. Correlational analysis revealed that pathogenic bacteria depleted by abx correlate with GFAP&#x2009;+&#x2009;astrocytosis, PAAs, and astrocyte morphological changes. Finally, we determined that abx-mediated reduction in GFAP&#x2009;+&#x2009;astrocytosis, PAAs, and&#xa0;astrocytic C3 expression is independent of microglia. However, abx-induced astrocyte morphological alterations are dependent on the presence of microglia, suggesting that there is both microglial independent and dependent GMB control of reactive astrocyte phenotypes.<br><br>CONCLUSIONS: We show for the first time, in the context of amyloidosis, that the GMB plays an important role in controlling reactive astrocyte induction, morphology, and astrocyte recruitment to A&#x3b2; plaques. GMB regulation of these astrocytic phenotypes is both independent and dependent on microglia.}, }
@article {pmid37414899, year = {2023}, author = {Routy, B and Lenehan, JG and Miller, WH and Jamal, R and Messaoudene, M and Daisley, BA and Hes, C and Al, KF and Martinez-Gili, L and Punčochář, M and Ernst, S and Logan, D and Belanger, K and Esfahani, K and Richard, C and Ninkov, M and Piccinno, G and Armanini, F and Pinto, F and Krishnamoorthy, M and Figueredo, R and Thebault, P and Takis, P and Magrill, J and Ramsay, L and Derosa, L and Marchesi, JR and Parvathy, SN and Elkrief, A and Watson, IR and Lapointe, R and Segata, N and Haeryfar, SMM and Mullish, BH and Silverman, MS and Burton, JP and Maleki Vareki, S}, title = {Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial.}, journal = {Nature medicine}, volume = {29}, number = {8}, pages = {2121-2132}, pmid = {37414899}, issn = {1546-170X}, support = {MC_PC_12025/MRC_/Medical Research Council/United Kingdom ; PJT &#x2013; 156295//CIHR/Canada ; MOP 389137//CIHR/Canada ; PJT-178341//CIHR/Canada ; }, mesh = {Animals ; Mice ; *Fecal Microbiota Transplantation/methods ; Immune Checkpoint Inhibitors ; Feces/microbiology ; *Melanoma/therapy ; Immunotherapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) represents a potential strategy to overcome resistance to immune checkpoint inhibitors in patients with refractory melanoma; however, the role of FMT in first-line treatment settings has not been evaluated. We conducted a multicenter phase I trial combining healthy donor FMT with the PD-1 inhibitors nivolumab or pembrolizumab in 20 previously untreated patients with advanced melanoma. The primary end point was safety. No grade 3 adverse events were reported from FMT alone. Five patients (25%) experienced grade 3 immune-related adverse events from combination therapy. Key secondary end points were objective response rate, changes in gut microbiome composition and systemic immune and metabolomics analyses. The objective response rate was 65% (13 of 20), including four (20%) complete responses. Longitudinal microbiome profiling revealed that all patients engrafted strains from their respective donors; however, the acquired similarity between donor and patient microbiomes only increased over time in responders. Responders experienced an enrichment of immunogenic and a loss of deleterious bacteria following FMT. Avatar mouse models confirmed the role of healthy donor feces in increasing anti-PD-1 efficacy. Our results show that FMT from healthy donors is safe in the first-line setting and warrants further investigation in combination with immune checkpoint inhibitors. ClinicalTrials.gov identifier NCT03772899 .}, }
@article {pmid37414494, year = {2023}, author = {Hashimoto, K}, title = {Neuroinflammation through the vagus nerve-dependent gut-microbiota-brain axis in treatment-resistant depression.}, journal = {Progress in brain research}, volume = {278}, number = {}, pages = {61-77}, doi = {10.1016/bs.pbr.2023.01.003}, pmid = {37414494}, issn = {1875-7855}, mesh = {Humans ; Depression/drug therapy ; *Depressive Disorder, Major/drug therapy ; Neuroinflammatory Diseases ; *Microbiota ; Antidepressive Agents/pharmacology/therapeutic use ; Inflammation/therapy ; Vagus Nerve ; Brain ; }, abstract = {Neuroinflammation plays a key role in the pathogenesis of major depressive disorder (MDD), including treatment-resistant depression (TRD). Patients with TRD have higher levels of inflammatory biomarkers compared with responders to antidepressants. Multiple lines of evidence suggest that the gut-microbiota-brain axis via the vagus nerve plays a key role in neuroinflammation. Preclinical and clinical data suggest that fecal microbiota transplantation (FMT) from MDD patients or rodents with depression-like behaviors cause depression-like behaviors in rodents through systemic inflammation. Importantly, subdiaphragmatic vagotomy blocked these depression-like phenotypes and systemic inflammation in rodents after FMT of depression-related microbes. Subdiaphragmatic vagotomy also blocked the antidepressant-like effects of serotonergic antidepressants in rodents. Preclinical findings suggest that the new antidepressant, (R)-ketamine (or arketamine), may restore the altered composition of gut microbiota in rodents with depression-like behaviors, contributing to the beneficial effects of arketamine. In this chapter, the author reviews the role of the vagus nerve-dependent gut-microbiota-brain axis in depression (including TRD), and also discuss the potential of FMT, vagus nerve stimulation, and arketamine for the treatment of TRD.}, }
@article {pmid37408823, year = {2023}, author = {Zhang, L and Yang, L and Chu, H}, title = {Targeting Gut Microbiota for the Treatment of Primary Biliary Cholangitis: From Bench to Bedside.}, journal = {Journal of clinical and translational hepatology}, volume = {11}, number = {4}, pages = {958-966}, pmid = {37408823}, issn = {2310-8819}, abstract = {Primary biliary cholangitis (PBC) is a complex cholestatic liver disease with an unresolved etiology. The gut microbiota is composed of a dynamic community of bacteria, archaea, fungi, and viruses that have a key role in physiological processes related to nutrition, immunity, and host defense responses. A number of recent studies found that the composition of the gut microbiota of PBC patients was significantly altered, and reported that gut dysbiosis might arise during PBC development because of the close interactions of the liver and the gut. In light of the growing interest in this topic, the focus of this review is to characterize PBC gut microbiota alterations, the correlation between PBC pathology and the gut microbiota, and prospective therapies that target the altered gut microbiota, such as probiotics and fecal microbiota transplantation.}, }
@article {pmid37408039, year = {2023}, author = {Bo, T and Liu, H and Liu, M and Liu, Q and Li, Q and Cong, Y and Luo, Y and Wang, Y and Yu, B and Pu, T and Wang, L and Wang, Z and Wang, D}, title = {Mechanism of inulin in colic and gut microbiota of captive Asian elephant.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {148}, pmid = {37408039}, issn = {2049-2618}, mesh = {Animals ; Mice ; Inulin ; *Elephants/genetics ; Prebiotics/analysis ; *Gastrointestinal Microbiome/genetics ; *Colic ; RNA, Ribosomal, 16S/genetics ; Fatty Acids, Volatile/analysis ; }, abstract = {BACKGROUND: Gut microbiota have a complex role on the survivability, digestive physiology, production, and growth performance in animals. Recent studies have emphasized the effects of prebiotics therapy on the gut disease, but the relationship between elephant gut-related diseases and prebiotics remains elusive. Here, a case study was undertaken to evaluate the mechanism of inulin treatment in colic in Asian elephant (Elephas maximus Linnaeus).<br><br>METHODS: Fecal samples were collected from a sick elephant and four healthy elephants. Analysis of microbial profile was carried out by 16S rRNA sequencing, and the short chain fatty acids were tested by gas chromatography. The physiological function of "inulin-microbiota" of elephant was verified in mice by fecal microbial transplantation (FMT). The expression of related proteins was determined by Western blotting and qPCR.<br><br>RESULTS: (1) Eating inulin can cure gut colic of the sick elephant and changed gut microbiota. (2) It was found that "inulin microbiota" from the post-treatment elephants can promote the proliferation of intestinal cells, increase the utilization of short chain fatty acids (SCFAs), maintain intestinal barrier, and reduce the inflammation in mice. (3) The mechanism was inulin-gut microbiota-SCFAs-immune barrier.<br><br>CONCLUSIONS: Inulin contributed to rehabilitate the gut microbiota and gut immune barrier of the elephant with colic. This provides reasonable verification for using prebiotics to treat the colic in captive elephants. Prebiotics will foresure play an increasingly important role in disease prevention and treatment of captive animals in the future. Video Abstract.}, }
@article {pmid37407171, year = {2023}, author = {Sheng, W and Xu, W and Ding, J and Lu, B and Liu, L and He, Q and Zhou, Q}, title = {Guijiajiao (Colla Carapacis et Plastri, CCP) prevents male infertility via gut microbiota modulation.}, journal = {Chinese journal of natural medicines}, volume = {21}, number = {6}, pages = {403-410}, doi = {10.1016/S1875-5364(23)60471-6}, pmid = {37407171}, issn = {1875-5364}, mesh = {Humans ; Rats ; Male ; Animals ; *Gastrointestinal Microbiome ; Lipopolysaccharides/pharmacology ; RNA, Ribosomal, 16S ; Semen ; Sperm Motility ; *Infertility, Male/chemically induced/prevention &amp; control ; Testosterone ; }, abstract = {Male infertility is a significant cause of psychosocial and marital distress in approximately 50% of couples who are unable to conceive, with male factors being the underlying cause. Guijiajiao (Colla Carapacis et Plastri, CCP) is a Traditional Chinese Medicine commonly used to treat male infertility. The present study aimed to investigate the potential mechanisms underlying the preventive effects of CCP on male infertility. An infertile male rat model was established using cyclophosphamide (CTX), and CCP was administered for both treatment and prevention. Fecal microbiota transplantation (FMT) was also performed to explore the role of gut microbiota in the CCP-mediated prevention of male infertility in rats. Sperm motility and concentration were determined using a semi-automatic sperm classification analyzer. Subsequently, histopathological analysis using HE staining was performed to examine the changes in the small intestine and testis. Moreover, the serum levels of lipopolysaccharide (LPS) and testosterone were measured by ELISA. In addition, immunohistochemistry was conducted to detect CD3 expression in the small intestine, while RT-qPCR was employed to assess the expressions of interleukin-1 beta (IL-1β), cluster of differentiation 3 (CD3), Monocyte chemoattractant protein-1 (MCP-1), and C-X-C motif chemokine ligand 10 (CXCL-10) in the small intestine and epididymis. Finally, gut microbiota was analyzed by 16S rRNA sequencing. CCP improved sperm motility, number, and concentration in CTX-induced infertile male rats. CCP increased the serum testosterone level, inhibited the immune cell infiltration of the intestinal lamina propria, and promoted the aggregation of CD3[+] T cells in CTX-induced male infertility rats. CCP also inhibited the expressions of MCP-1, CXCL-10, and IL-1β in the epididymis of male infertility rats. At the genus level, CTX led to a reduction in the abundance of Lactobacillus, Clostridia_UCG.014, and Romboutsia in the intestinal tract of rats. In contrast, CCP decreased the abundance of Ruminococcus and increased the abundance of Romboutsia in infertile male rats. Additionally, FMT experiments proved that the gut microbiota of CCP-treated rats facilitated testicular tissue recovery and spermatogenesis while also reducing the serum LPS level in infertile male rats. CCP improves the spermatogenic ability of infertile male rats by restoring gut microbiota diversity and inhibiting epididymal inflammation.}, }
@article {pmid37406338, year = {2023}, author = {Ye, L and Chen, H and Tsim, KWK and Shen, X and Li, X and Li, X and Lei, H and Liu, Y}, title = {Aflatoxin B1 Induces Inflammatory Liver Injury via Gut Microbiota in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {28}, pages = {10787-10797}, doi = {10.1021/acs.jafc.3c02617}, pmid = {37406338}, issn = {1520-5118}, mesh = {Mice ; Humans ; Animals ; Aflatoxin B1/toxicity/metabolism ; *Gastrointestinal Microbiome ; *Chemical and Drug Induced Liver Injury, Chronic/metabolism ; Liver/metabolism ; *Aflatoxins/metabolism ; Inflammation/metabolism ; }, abstract = {Aflatoxin B1 (AFB1), a potent food-borne hepatocarcinogen, is the most toxic aflatoxin that induces liver injury in humans and animals. Species-specific sensitivities of aflatoxins cannot be fully explained by differences in the metabolism of AFB1 between animal species. The gut microbiota are critical in inflammatory liver injury, but it remains to reveal the role of gut microbiota in AFB1-induced liver injury. Here, mice were gavaged with AFB1 for 28 days. Then, the modulation of gut microbiota, colonic barrier, and liver pyroptosis and inflammation were analyzed. To further verify the direct role of gut microbiota in AFB1-induced liver injury, mice were treated with antibiotic mixtures (ABXs) to deplete the microbiota, and fecal microbiota transplantation (FMT) was conducted. The treatment of AFB1 in mice altered gut microbiota composition, such as increasing the relative abundance of Bacteroides, Parabacteroides, and Lactobacillus, inducing colonic barrier dysfunction and promoting liver pyroptosis. In ABX-treated mice, AFB1 had little effect on the colonic barrier and liver pyroptosis. Notably, after FMT, in which the mice were colonized with gut microbiota from AFB1-treated mice, colonic barrier dysfunction, and liver pyroptosis and inflammation were obliviously identified. We proposed that the gut microbiota directly participated in AFB1-induced liver pyroptosis and inflammation. These results provide new insights into the mechanisms of AFB1 hepatotoxicity and pave a window for new targeted interventions to prevent or reduce AFB1 hepatotoxicity.}, }
@article {pmid37405390, year = {2023}, author = {Kamath, S and Stringer, AM and Prestidge, CA and Joyce, P}, title = {Targeting the gut microbiome to control drug pharmacomicrobiomics: the next frontier in oral drug delivery.}, journal = {Expert opinion on drug delivery}, volume = {20}, number = {10}, pages = {1315-1331}, doi = {10.1080/17425247.2023.2233900}, pmid = {37405390}, issn = {1744-7593}, mesh = {*Gastrointestinal Microbiome ; Pharmaceutical Preparations/metabolism ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {INTRODUCTION: The trillions of microorganisms that comprise the gut microbiome form dynamic bidirectional interactions with orally administered drugs and host health. These relationships can alter all aspects of drug pharmacokinetics and pharmacodynamics (PK/PD); thus, there is a desire to control these interactions to maximize therapeutic efficacy. Attempts to modulate drug-gut microbiome interactions have spurred advancements within the field of 'pharmacomicrobiomics' and are poised to become the next frontier of oral drug delivery.<br><br>AREAS COVERED: This review details the bidirectional interactions that exist between oral drugs and the gut microbiome, with clinically relevant case examples outlining a clear motive for controlling pharmacomicrobiomic interactions. Specific focus is attributed to novel and advanced strategies that have demonstrated success in mediating drug-gut microbiome interactions.<br><br>EXPERT OPINION: Co-administration of gut-active supplements (e.g. pro- and pre-biotics), innovative drug delivery vehicles, and strategic polypharmacy serve as the most promising and clinically viable approaches for controlling pharmacomicrobiomic interactions. Targeting the gut microbiome through these strategies presents new opportunities for improving therapeutic efficacy by precisely mediating PK/PD, while mitigating metabolic disturbances caused by drug-induced gut dysbiosis. However, successfully translating preclinical potential into clinical outcomes relies on overcoming key challenges related to interindividual variability in microbiome composition and study design parameters.}, }
@article {pmid37404180, year = {2023}, author = {Natarajan, A and Fremin, BJ and Schmidtke, DT and Wolfe, MK and Zlitni, S and Graham, KE and Brooks, EF and Severyn, CJ and Sakamoto, KM and Lacayo, NJ and Kuersten, S and Koble, J and Caves, G and Kaplan, I and Singh, U and Jagannathan, P and Rezvani, AR and Bhatt, AS and Boehm, AB}, title = {The Tomato Brown Rugose Fruit Virus Movement Protein Gene Is a Novel Microbial Source Tracking Marker.}, journal = {Applied and environmental microbiology}, volume = {89}, number = {7}, pages = {e0058323}, pmid = {37404180}, issn = {1098-5336}, support = {DK098132/GF/NIH HHS/United States ; DGE-1656518/GF/NIH HHS/United States ; R01 AI148623/GF/NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Wastewater ; *Solanum lycopersicum ; Fruit ; Biomarkers ; Feces/microbiology ; Environmental Monitoring/methods ; }, abstract = {Microbial source tracking (MST) identifies sources of fecal contamination in the environment using host-associated fecal markers. While there are numerous bacterial MST markers that can be used herein, there are few such viral markers. Here, we designed and tested novel viral MST markers based on tomato brown rugose fruit virus (ToBRFV) genomes. We assembled eight nearly complete genomes of ToBRFV from wastewater and stool samples from the San Francisco Bay Area in the United States. Next, we developed two novel probe-based reverse transcription-PCR (RT-PCR) assays based on conserved regions of the ToBRFV genome and tested the markers' sensitivities and specificities using human and non-human animal stool as well as wastewater. The ToBRFV markers are sensitive and specific; in human stool and wastewater, they are more prevalent and abundant than a commonly used viral marker, the pepper mild mottle virus (PMMoV) coat protein (CP) gene. We used the assays to detect fecal contamination in urban stormwater samples and found that the ToBRFV markers matched cross-assembly phage (crAssphage), an established viral MST marker, in prevalence across samples. Taken together, these results indicate that ToBRFV is a promising viral human-associated MST marker. IMPORTANCE Human exposure to fecal contamination in the environment can cause transmission of infectious diseases. Microbial source tracking (MST) can identify sources of fecal contamination so that contamination can be remediated and human exposures can be reduced. MST requires the use of host-associated MST markers. Here, we designed and tested novel MST markers from genomes of tomato brown rugose fruit virus (ToBRFV). The markers are sensitive and specific to human stool and highly abundant in human stool and wastewater samples.}, }
@article {pmid37404011, year = {2023}, author = {Rooney, AM and Cochrane, K and Fedsin, S and Yao, S and Anwer, S and Dehmiwal, S and Hota, S and Poutanen, S and Allen-Vercoe, E and Coburn, B and , }, title = {A microbial consortium alters intestinal Pseudomonadota and antimicrobial resistance genes in individuals with recurrent Clostridioides difficile infection.}, journal = {mBio}, volume = {14}, number = {4}, pages = {e0348222}, pmid = {37404011}, issn = {2150-7511}, mesh = {Humans ; Microbial Consortia ; Anti-Bacterial Agents/pharmacology ; *Clostridioides difficile ; *Gastrointestinal Microbiome ; Drug Resistance, Bacterial ; Fecal Microbiota Transplantation ; *Clostridium Infections/therapy/microbiology ; Feces/microbiology ; *Microbiota ; Treatment Outcome ; }, abstract = {Intestinal colonization with pathogens and antimicrobial-resistant organisms (AROs) is associated with increased risk of infection. Fecal microbiota transplant (FMT) has successfully been used to cure recurrent Clostridioides difficile infection (rCDI) and to decolonize intestinal AROs. However, FMT has significant practical barriers to safe and broad implementation. Microbial consortia represent a novel strategy for ARO and pathogen decolonization, with practical and safety advantages over FMT. We undertook an investigator-initiated analysis of stool samples collected from previous interventional studies of a microbial consortium, microbial ecosystem therapeutic (MET-2), and FMT for rCDI before and after treatment. Our aim was to assess whether MET-2 was associated with decreased Pseudomonadota (Proteobacteria) and antimicrobial resistance gene (ARG) burden with similar effects to FMT. Participants were selected for inclusion if baseline stool had Pseudomonadota relative abundance ≥10%. Pre- and post-treatment Pseudomonadota relative abundance, total ARGs, and obligate anaerobe and butyrate-producer relative abundances were determined by shotgun metagenomic sequencing. MET-2 administration had similar effects to FMT on microbiome outcomes. The median Pseudomonadota relative abundance decreased by four logs after MET-2 treatment, a greater decrease than that observed after FMT. Total ARGs decreased, while beneficial obligate anaerobe and butyrate-producer relative abundances increased. The observed microbiome response remained stable over 4 months post-administration for all outcomes. IMPORTANCE Overgrowth of intestinal pathogens and AROs is associated with increased risk of infection. With the rise in antimicrobial resistance, new therapeutic strategies that decrease pathogen and ARO colonization in the gut are needed. We evaluated whether a microbial consortium had similar effects to FMT on Pseudomonadota abundances and ARGs as well as obligate anaerobes and beneficial butyrate producers in individuals with high Pseudomonadota relative abundance at baseline. This study provides support for a randomized, controlled clinical trial of microbial consortia (such as MET-2) for ARO decolonization and anaerobe repletion.}, }
@article {pmid37403348, year = {2023}, author = {Ren, H and Wu, Q and Sun, Z and Fang, M and Liu, J and Luo, J}, title = {Research progress and treatment of radiation enteritis and gut microbiota.}, journal = {Radiation oncology journal}, volume = {41}, number = {2}, pages = {61-68}, pmid = {37403348}, issn = {2234-1900}, support = {82073339//National Natural Science Foundation of China/ ; CJ20210166//Changzhou Sci&amp;Tech Program/ ; CJ20220092//Changzhou Sci&amp;Tech Program/ ; 202209030703//Development Plan of Medical Science and Technology of Shandong province/ ; }, abstract = {Radiation enteritis is a kind of intestinal radiation injury in patients with pelvic and retroperitoneal malignancies after radiotherapy, and its occurrence and development process are very complicated. At present, studies have confirmed that intestinal microecological imbalance is an important factor in the formation of this disease. Abdominal radiation causes changes in the composition of the flora and a decrease in its diversity, which is mainly manifested by a decrease in beneficial bacterial species such as Lactobacilli and Bifidobacteria. Intestinal dysbacteriosis aggravates radiation enteritis, weakens the function of the intestinal epithelial barrier, and promotes the expression of inflammatory factors, thereby aggravating the occurrence of enteritis. Given the role of the microbiome in radiation enteritis, we suggest that the gut microbiota may be a potential biomarker for the disease. Treatment methods such as probiotics, antibiotics, and fecal microbiota transplantation are ways to correct the microbiota and may be an effective way to prevent and treat radiation enteritis. Based on a review of the relevant literature, this paper reviews the mechanism and treatment of intestinal microbes in radiation enteritis.}, }
@article {pmid37402856, year = {2023}, author = {Hashimoto, K}, title = {Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein-Barr virus and the gut-brain axis.}, journal = {Molecular psychiatry}, volume = {28}, number = {12}, pages = {4968-4976}, pmid = {37402856}, issn = {1476-5578}, support = {21H00184//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05612//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H02846//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; }, mesh = {Humans ; *Brain/virology ; *Brain-Gut Axis/physiology ; *COVID-19/complications ; Epstein-Barr Virus Infections/complications ; *Gastrointestinal Microbiome/physiology ; *Herpesvirus 4, Human/pathogenicity ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in a serious public health burden worldwide. In addition to respiratory, heart, and gastrointestinal symptoms, patients infected with SARS-CoV-2 experience a number of persistent neurological and psychiatric symptoms, known as long COVID or "brain fog". Studies of autopsy samples from patients who died from COVID-19 detected SARS-CoV-2 in the brain. Furthermore, increasing evidence shows that Epstein-Barr virus (EBV) reactivation after SARS-CoV-2 infection might play a role in long COVID symptoms. Moreover, alterations in the microbiome after SARS-CoV-2 infection might contribute to acute and long COVID symptoms. In this article, the author reviews the detrimental effects of COVID-19 on the brain, and the biological mechanisms (e.g., EBV reactivation, and changes in the gut, nasal, oral, or lung microbiomes) underlying long COVID. In addition, the author discusses potential therapeutic approaches based on the gut-brain axis, including plant-based diet, probiotics and prebiotics, fecal microbiota transplantation, and vagus nerve stimulation, and sigma-1 receptor agonist fluvoxamine.}, }
@article {pmid37402619, year = {2024}, author = {Delplanque, M and Benech, N and Rolhion, N and Oeuvray, C and Straube, M and Galbert, C and Brot, L and Henry, T and Jamilloux, Y and Savey, L and Grateau, G and Sokol, H and Georgin-Lavialle, S}, title = {Gut microbiota alterations are associated with phenotype and genotype in familial Mediterranean fever.}, journal = {Rheumatology (Oxford, England)}, volume = {63}, number = {4}, pages = {1039-1048}, doi = {10.1093/rheumatology/kead322}, pmid = {37402619}, issn = {1462-0332}, support = {//Soci&#xe9;t&#xe9; Nationale Fran&#xe7;aise de M&#xe9;decine Interne-REMI/ ; }, mesh = {Humans ; *Familial Mediterranean Fever/drug therapy/genetics/complications ; *Gastrointestinal Microbiome/genetics ; Genotype ; Colchicine/therapeutic use ; Phenotype ; Mutation ; Pyrin/genetics ; *Clostridiales ; }, abstract = {OBJECTIVE: FMF is the most common monogenic autoinflammatory disease associated with MEFV mutations. Disease phenotype and response to treatment vary from one patient to another, despite similar genotype, suggesting the role of environmental factors. The objective of this study was to analyse the gut microbiota of a large cohort of FMF patients in relation to disease characteristics.<br><br>METHODS: The gut microbiotas of 119 FMF patients and 61 healthy controls were analysed using 16&#x2009;s rRNA gene sequencing. Associations between bacterial taxa, clinical characteristics, and genotypes were evaluated using multivariable association with linear models (MaAslin2), adjusting on age, sex, genotype, presence of AA amyloidosis (n&#x2009;=&#x2009;17), hepatopathy (n&#x2009;=&#x2009;5), colchicine intake, colchicine resistance (n&#x2009;=&#x2009;27), use of biotherapy (n&#x2009;=&#x2009;10), CRP levels, and number of daily faeces. Bacterial network structures were also analysed.<br><br>RESULTS: The gut microbiotas of FMF patients differ from those of controls in having increased pro-inflammatory bacteria, such as the Enterobacter, Klebsiella and Ruminococcus gnavus group. Disease characteristics and resistance to colchicine correlated with homozygous mutations and were associated with specific microbiota alteration. Colchicine treatment was associated with the expansion of anti-inflammatory taxa such as Faecalibacterium and Roseburia, while FMF severity was associated with expansion of the Ruminococcus gnavus group and Paracoccus. Colchicine-resistant patients exhibited an alteration of the bacterial network structure, with decreased intertaxa connectivity.<br><br>CONCLUSION: The gut microbiota of FMF patients correlates with disease characteristics and severity, with an increase in pro-inflammatory taxa in the most severe patients. This suggests a specific role for the gut microbiota in shaping FMF outcomes and response to treatment.}, }
@article {pmid37401755, year = {2023}, author = {Ronkainen, A and Khan, I and Krzyżewska-Dudek, E and Hiippala, K and Freitag, TL and Satokari, R}, title = {In vitro adhesion, pilus expression, and in vivo amelioration of antibiotic-induced microbiota disturbance by Bifidobacterium spp. strains from fecal donors.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2229944}, pmid = {37401755}, issn = {1949-0984}, mesh = {Animals ; Mice ; Anti-Bacterial Agents/pharmacology ; Bifidobacterium ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; *Clostridioides difficile ; Mice, Inbred C57BL ; Feces/microbiology ; Fecal Microbiota Transplantation ; *Microbiota ; *Clostridium Infections/microbiology ; }, abstract = {Fecal microbiota transplantation (FMT) is used routinely to treat recurrent Clostridioides difficile infection (rCDI) and investigated as a treatment for numerous conditions associated with gut microbiota alterations. Metagenomic analyses have indicated that recipient colonization by donor bacteria may be associated with favorable clinical outcomes. Bifidobacteria are abundant gut commensals associated with health. We have previously demonstrated that Bifidobacterium strains transferred in FMT can colonize recipients in long term, at least for a year, and recovered such strains by cultivation. This study addressed in vitro adhesion and pilus gene expression of long-term colonizing Bifidobacterium strains from FMT donors as well as in vivo colonization and capability to ameliorate antibiotic-induced microbiota disturbance. RNA-Seq differential gene expression analysis showed that the strongly adherent B. longum strains DY_pv11 and DX_pv23 expressed tight adherence and sortase-dependent pilus genes, respectively. Two B. longum strains, adherent DX_pv23 and poorly adhering DX_pv18, were selected to address in vivo colonization and efficacy to restore antibiotic-disturbed microbiota in C57BL/6 murine model. DX_pv23 colonized mice transiently with a rate comparable to that of the B. animalis BB-12 used as a reference. Although long-term colonization was not observed with any of the three strains, 16S rRNA gene profiling revealed that oral administration of DX_pv23 enhanced the recovery of antibiotic-disturbed microbiota to the original configuration significantly better than the other strains. The findings suggest that selected strains from FMT donors, such as DX_pv23 in this study, may have therapeutic potential by in vitro expression of colonization factors and boosting endogenous gut microbiota.}, }
@article {pmid37400423, year = {2023}, author = {Wang, L and Tu, YX and Chen, L and Zhang, Y and Pan, XL and Yang, SQ and Zhang, SJ and Li, SH and Yu, KC and Song, S and Xu, HL and Yin, ZC and Yue, JQ and Ni, QL and Tang, T and Zhang, JL and Guo, M and Zhang, S and Yao, F and Liang, XJ and Chen, ZX}, title = {Male-Biased Gut Microbiome and Metabolites Aggravate Colorectal Cancer Development.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {10}, number = {25}, pages = {e2206238}, pmid = {37400423}, issn = {2198-3844}, support = {2021ABA011//The science and technology major program of Hubei Province/ ; 2021hszd012//Foundation of Hubei Hongshan Laboratory/ ; 2022SWZX04//Research Projects of Biomedical Center of Hubei Cancer Hospital/ ; SZYJY2021010//HZAU-AGIS Cooperation Fund/ ; 2662020PY001//Fundamental Research Funds for the Central Universities/ ; WJ2021Z001//The Health Commission of Hubei Province/ ; //Huazhong Agricultural University/ ; }, mesh = {Male ; Female ; Animals ; Mice ; *Colorectal Neoplasms/pathology ; *Gastrointestinal Microbiome ; Dextran Sulfate ; Carcinogenesis ; Cell Transformation, Neoplastic ; }, abstract = {Men demonstrate higher incidence and mortality rates of colorectal cancer (CRC) than women. This study aims to explain the potential causes of such sexual dimorphism in CRC from the perspective of sex-biased gut microbiota and metabolites. The results show that sexual dimorphism in colorectal tumorigenesis is observed in both Apc[Min/] [+] mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice with male mice have significantly larger and more tumors, accompanied by more impaired gut barrier function. Moreover, pseudo-germ mice receiving fecal samples from male mice or patients show more severe intestinal barrier damage and higher level of inflammation. A significant change in gut microbiota composition is found with increased pathogenic bacteria Akkermansia muciniphila and deplets probiotic Parabacteroides goldsteinii in both male mice and pseudo-germ mice receiving fecal sample from male mice. Sex-biased gut metabolites in pseudo-germ mice receiving fecal sample from CRC patients or CRC mice contribute to sex dimorphism in CRC tumorigenesis through glycerophospholipids metabolism pathway. Sexual dimorphism in tumorigenesis of CRC mouse models. In conclusion, the sex-biased gut microbiome and metabolites contribute to sexual dimorphism in CRC. Modulating sex-biased gut microbiota and metabolites could be a potential sex-targeting therapeutic strategy of CRC.}, }
@article {pmid37398134, year = {2023}, author = {Willis, KA and Silverberg, M and Martin, I and Abdelgawad, A and Karabayir, I and Halloran, BA and Myers, ED and Desai, JP and White, CT and Lal, CV and Ambalavanan, N and Peters, BM and Jain, VG and Akbilgic, O and Tipton, L and Jilling, T and Cormier, SA and Pierre, JF and Talati, AJ}, title = {The fungal intestinal microbiota predict the development of bronchopulmonary dysplasia in very low birthweight newborns.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.05.29.23290625}, pmid = {37398134}, support = {K08 HL151907/HL/NHLBI NIH HHS/United States ; L40 HL159581/HL/NHLBI NIH HHS/United States ; }, abstract = {RATIONALE: Bronchopulmonary dysplasia (BPD) is the most common morbidity affecting very preterm infants. Gut fungal and bacterial microbial communities contribute to multiple lung diseases and may influence BPD pathogenesis.<br><br>METHODS: We performed a prospective, observational cohort study comparing the multikingdom fecal microbiota of 144 preterm infants with or without moderate to severe BPD by sequencing the bacterial 16S and fungal ITS2 ribosomal RNA gene. To address the potential causative relationship between gut dysbiosis and BPD, we used fecal microbiota transplant in an antibiotic-pseudohumanized mouse model. Comparisons were made using RNA sequencing, confocal microscopy, lung morphometry, and oscillometry.<br><br>RESULTS: We analyzed 102 fecal microbiome samples collected during the second week of life. Infants who later developed BPD showed an obvious fungal dysbiosis as compared to infants without BPD (NoBPD, p = 0.0398, permutational multivariate ANOVA). Instead of fungal communities dominated by Candida and Saccharomyces, the microbiota of infants who developed BPD were characterized by a greater diversity of rarer fungi in less interconnected community architectures. On successful colonization, the gut microbiota from infants with BPD augmented lung injury in the offspring of recipient animals. We identified alterations in the murine intestinal microbiome and transcriptome associated with augmented lung injury.<br><br>CONCLUSIONS: The gut fungal microbiome of infants who will develop BPD is dysbiotic and may contribute to disease pathogenesis.}, }
@article {pmid37397151, year = {2023}, author = {Chakraborty, PS and Daniel, R and Navarro, FA}, title = {Non-pharmacologic approaches to treatment of pediatric functional abdominal pain disorders.}, journal = {Frontiers in pediatrics}, volume = {11}, number = {}, pages = {1118874}, pmid = {37397151}, issn = {2296-2360}, abstract = {Functional abdominal pain disorders (FAPDs) affect up to 25% of children in the United States. These disorders are more recently known as disorders of "brain-gut" interaction. The diagnosis is based on the ROME IV criteria, and requires the absence of an organic condition to explain the symptoms. Although these disorders are not completely understood, several factors have been involved in the pathophysiology including disordered gut motility, visceral hypersensitivity, allergies, anxiety/stress, gastrointestinal infection/inflammation, as well dysbiosis of the gut microbiome. The pharmacologic and non-pharmacologic treatments for FAPDs are directed to modifying these pathophysiologic mechanisms. This review aims to summarize the non-pharmacologic interventions used in the treatment of FAPDs including dietary modifications, manipulation of the gut microbiome (neutraceuticals, prebiotics, probiotics, synbiotics and fecal microbiota transplant) and psychological interventions that addresses the "brain" component of the brain-gut axis (cognitive behavioral therapy, hypnotherapy, breathing and relaxation techniques). In a survey conducted at a large academic pediatric gastroenterology center, 96% of patients with functional pain disorders reported using at least 1 complementary and alternative medicine treatment to ameliorate symptoms. The paucity of data supporting most of the therapies discussed in this review underscores the need for large randomized controlled trials to assess their efficacy and superiority compared to other treatments.}, }
@article {pmid37395845, year = {2023}, author = {Baum, J and Lax, H and Lehmann, N and Merkel-Jens, A and Beelen, DW and Jöckel, KH and Dührsen, U}, title = {Preventive health care in blood cancer survivors: results from the ABC study.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {13}, pages = {11531-11540}, pmid = {37395845}, issn = {1432-1335}, support = {01GY1341//Bundesministerium f&#xfc;r Bildung und Forschung/ ; }, mesh = {Humans ; *Cancer Survivors ; Retrospective Studies ; *Neoplasms/diagnosis ; Survivors ; Preventive Health Services ; *Hematologic Neoplasms ; }, abstract = {BACKGROUND: Blood cancer survivors are at increased risk for second primary malignancies, cardiovascular diseases, and infections. Little is known about preventive care in blood cancer survivors.<br><br>METHODS: Our questionnaire-based study included blood cancer patients diagnosed at the University Hospital of Essen before 2010, with a&#x2009;&#x2265;&#x2009;3-year interval from the last intense treatment. One section of the retrospective study covered preventive care (cancer screening, cardiovascular screening, vaccination).<br><br>RESULTS: Preventive care was delivered by a general practitioner for 1100 of 1504 responding survivors (73.1%), by an oncologist for 125 (8.3%), by a general practitioner together with an oncologist for 156 (10.4%), and by other disciplines for 123 (8.2%). Cancer screening was more consistently performed by general practitioners than by oncologists. The converse was true for vaccination, with particularly high vaccination rates in allogeneic transplant recipients. Cardiovascular screening did not differ between care providers. Cancer and cardiovascular screening rates in survivors eligible for statutory prevention&#xa0;programs were higher than in the general population (skin cancer screening 71.1%; fecal occult blood testing 70.4%; colonoscopy 64.6%; clinical breast examination 92.1%; mammography 86.8%; cervical smear 86.0%; digital rectal examination 61.9%; blood pressure test 69.4%; urine glucose test 54.4%; blood lipid test 76.7%; information about overweight 71.0%). The Streptococcus pneumoniae vaccination rate was higher (37.0%) and the influenza vaccination rate was lower (57.0%) than in the general population.<br><br>CONCLUSIONS: Utilization of preventive care is high among German blood cancer survivors. To ensure widespread delivery and avoid redundancy, communication between oncologists and preventive care providers is essential.}, }
@article {pmid37394554, year = {2023}, author = {Terauchi, J}, title = {[Introduction of industry precompetitive consortium to promote microbiome based drug discovery in Japan].}, journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica}, volume = {158}, number = {4}, pages = {326-331}, doi = {10.1254/fpj.22112}, pmid = {37394554}, issn = {0015-5691}, mesh = {*Clostridioides difficile ; Japan ; *Microbiota ; Drug Discovery ; *Gastrointestinal Microbiome ; Drug Industry ; }, abstract = {With the advent of next-generation sequencers and subsequent large national projects by the U.S. and Europe, scientific information and knowledge have been dramatically accumulated on the microbiome and data associated with various diseases. Ever since the surprising highly successful efficacy of refractory C. difficile infectious disease by fecal microbiota transplantation is reported, microbiome modulation has been expected as a new approach for drug discovery. Therefore, lots of microbiome drug discovery ventures have sprung up and clinical pipelines in late-stage clinical development have already been created especially in U.S. and Europe. Unfortunately, Japan is lagging behind U.S. and Europe., as is often the case with other modalities such as the genome-based drug discovery. However, since pioneering research on gut microbiota began in Japan and has since been highly successful, the establishment of a domestic microbiome drug discovery infrastructure is long overdue. Under this environment, the Japan Microbiome Consortium, a general incorporated association established in 2017 to promote the industrial application of microbiome research, has been promoting pre-competitive collaborative activities with the participation of more than 30 domestic companies, including pharmaceutical companies, to build the microbiome drug discovery infrastructure. The consortium has been working on the construction of a drug discovery ecosystem that will lead to (1) a reliable measurement platform, (2) microbiome data in the healthy gut, and (3) microbiome drug discovery, by utilizing government projects. In this paper, we introduce the consortium and its activities to promote industrialization through pre-competitive collaborative activities.}, }
@article {pmid37392210, year = {2023}, author = {Coe, GL and Krout, IN and Munro-Ehrlich, M and Beamish, CR and Vorojeikina, D and Colman, DR and Boyd, EJ and Walk, ST and Rand, MD}, title = {Assessing the role of the gut microbiome in methylmercury demethylation and elimination in humans and gnotobiotic mice.}, journal = {Archives of toxicology}, volume = {97}, number = {9}, pages = {2399-2418}, pmid = {37392210}, issn = {1432-0738}, support = {T32 207026/ES/NIEHS NIH HHS/United States ; P30 ES001247/ES/NIEHS NIH HHS/United States ; ES001247/ES/NIEHS NIH HHS/United States ; R01 ES030940/ES/NIEHS NIH HHS/United States ; ES030940/ES/NIEHS NIH HHS/United States ; T32 ES007026/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; *Methylmercury Compounds/toxicity/metabolism ; *Gastrointestinal Microbiome ; *Microbiota ; Kinetics ; Demethylation ; }, abstract = {The risk of methylmercury (MeHg) toxicity following ingestion of contaminated foodstuffs (e.g., fish) is directly related to the kinetics of MeHg elimination among individuals. Yet, the factors driving the wide range of inter-individual variability in MeHg elimination within a population are poorly understood. Here, we investigated the relationship between MeHg elimination, gut microbiome demethylation activity, and gut microbiome composition using a coordinated human clinical trial and gnotobiotic mouse modeling approach together with metagenomic sequence analysis. We first observed MeHg elimination half-lives (t1/2) ranging from 28 to 90 days across 27 volunteers. Subsequently, we found that ingestion of a prebiotic induced changes in the gut microbiome and mixed effects (increased, decrease, and no effect) on elimination in these same individuals. Nonetheless, elimination rates were found to correlate with MeHg demethylation activity in cultured stool samples. In mice, attempts to remove the microbiome via generation of germ-free (GF) animals or through antibiotic (Abx) treatment both diminished MeHg demethylation to a similar extent. While both conditions substantially slowed elimination, Abx treatment resulted in significantly slower elimination than the GF condition, indicating an additional role for host-derived factors in supporting elimination. Human fecal microbiomes transplanted to GF mice restored elimination rates to that seen in control mice. Metagenomic sequence analysis of human fecal DNA did not identify genes encoding proteins typically involved in demethylation (e.g., merB, organomercury lyase). However, the abundance of several anaerobic taxa, notably Alistipes onderdonkii, were positively correlated with MeHg elimination. Surprisingly, mono-colonization of GF free mice with A. onderdonkii did not restore MeHg elimination to control levels. Collectively, our findings indicate the human gut microbiome uses a non-conventional pathway of demethylation to increase MeHg elimination that relies on yet to be resolved functions encoded by the gut microbes and the hostClinical Trial NCT04060212, prospectively registered 10/1/2019.}, }
@article {pmid37390712, year = {2023}, author = {Ling, H and Lin, Y and Bao, W and Xu, N and Chen, L and Zhao, L and Liu, C and Shen, Y and Zhang, D and Gong, Y and Gao, Q and Wang, J and Jin, S}, title = {Erythropoietin-mediated IL-17 F attenuates sepsis-induced gut microbiota dysbiosis and barrier dysfunction.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {165}, number = {}, pages = {115072}, doi = {10.1016/j.biopha.2023.115072}, pmid = {37390712}, issn = {1950-6007}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Dysbiosis/therapy ; Interleukin-17 ; *Erythropoietin/pharmacology ; *Sepsis/complications ; }, abstract = {Septic gut damage is critical in the progression of sepsis and multiple organ failure, characterized by gut microbiota dysbiosis and epithelium deficiency in the gut barrier. Recent studies highlight the protective effects of Erythropoietin (EPO) on multiple organs. The present study found that EPO treatment significantly alleviated the survival rate, suppressed inflammatory responses, and ameliorated intestine damage in mice with sepsis. EPO treatment also reversed sepsis-induced gut microbiota dysbiosis. The protective role of EPO in the gut barrier and microbiota was impaired after EPOR knockout. Notably, we innovatively demonstrated that IL-17 F screened by transcriptome sequencing could ameliorate sepsis and septic gut damage including gut microbiota dysbiosis and barrier dysfunction, which was verified by IL-17 F-treated fecal microbiota transplantation (FMT) as well. Our findings highlight the protection effects of EPO-mediated IL-17 F in sepsis-induced gut damage by alleviating gut barrier dysfunction and restoring gut microbiota dysbiosis. EPO and IL-17 F may be potential therapeutic targets in septic patients.}, }
@article {pmid37390560, year = {2023}, author = {Chen, C and Chen, W and Ding, H and Wu, P and Zhang, G and Xie, K and Zhang, T}, title = {High-fat diet-induced gut microbiota alteration promotes lipogenesis by butyric acid/miR-204/ACSS2 axis in chickens.}, journal = {Poultry science}, volume = {102}, number = {9}, pages = {102856}, pmid = {37390560}, issn = {1525-3171}, mesh = {Animals ; Mice ; Butyric Acid/pharmacology ; Diet, High-Fat/adverse effects/veterinary ; *Gastrointestinal Microbiome ; Chickens/genetics ; Obesity/veterinary ; Lipogenesis ; Dysbiosis/veterinary ; RNA, Ribosomal, 16S ; *MicroRNAs/metabolism ; RNA, Messenger/metabolism ; Mice, Inbred C57BL ; }, abstract = {The gut microbiota is known to have significant involvement in the regulation of lipogenesis and adipogenesis, yet the mechanisms responsible for this relationship remain poorly understood. The current study aims to provide insight into the potential mechanisms by which the gut microbiota modulates lipogenesis in chickens. Using chickens fed with a normal-fat diet (NFD, n = 5) and high-fat diet (HFD, n = 5), we analyzed the correlation between gut microbiota, cecal metabolomics, and lipogenesis by 16s rRNA sequencing, miRNA and mRNA sequencing as well as targeted metabolomics analysis. The potential metabolite/miRNA/mRNA axis regulated by gut microbiota was identified using chickens treated with antibiotics (ABX, n = 5). The possible mechanism of gut microbiota regulating chicken lipogenesis was confirmed by fecal microbiota transplantation (FMT) from chickens fed with NFD to chickens fed with HFD (n = 5). The results showed that HFD significantly altered gut microbiota composition and enhanced chicken lipogenesis, with a significant correlation between 3. Furthermore, HFD significantly altered the hepatic miRNA expression profiles and reduced the abundance of hepatic butyric acid. Procrustes analysis indicated that the HFD-induced dysbiosis of the gut microbiota might affect the expression profiles of hepatic miRNA. Specifically, HFD-induced gut microbiota dysbiosis may reduce the abundance of butyric acid and downregulate the expression of miR-204 in the liver. Multiomics analysis identified ACSS2 as a target gene of miR-204. Gut microbiota depletion by an antibiotic cocktail (ABX) showed a gut microbiota-dependent manner in the abundance of butyric acid and the expression of miR-204/ACSS2, which have been observed to be significantly correlated. Fecal microbiota transplantation from NFD chickens into HFD chickens effectively attenuated the HFD-induced excessive lipogenesis, elevated the abundance of butyric acid and the relative expression of miR-204, and reduced the expression of ACSS2 in the liver. Mechanistically, our results showed that the gut microbiota plays an antiobesity role by regulating the butyric acid/miR-204/ACSS2 axis in chickens. This work contributed to a better understanding of the functions of gut microbiota in regulating chicken lipogenesis.}, }
@article {pmid37389459, year = {2023}, author = {Rocha, IM and Fonseca, DC and Torrinhas, RSM and Waitzberg, DL}, title = {Understanding the gut microbiota in cancer cachexia.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {26}, number = {5}, pages = {482-489}, doi = {10.1097/MCO.0000000000000957}, pmid = {37389459}, issn = {1473-6519}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome/physiology ; Cachexia/therapy/complications ; Quality of Life ; *Probiotics/therapeutic use ; *Neoplasms/complications ; Prebiotics ; *Synbiotics ; Inflammation/complications ; Dysbiosis/complications ; }, abstract = {PURPOSE OF REVIEW: Cachexia is a complex, multifactorial syndrome primarily characterized by weight loss, muscle wasting, anorexia, and systemic inflammation. It is prevalent in cancer patients and is associated with a poor prognosis, including lower resistance to intervention toxicity, quality of life, and survival, compared to patients without the syndrome. The gut microbiota and its metabolites have been shown to influence host metabolism and immune response. Our article reviews the current evidence suggesting a role of gut microbiota in the development and progression of cachexia, while discussing the potential mechanisms involved. We also describe promising interventions targeting gut microbiota aiming to improve outcomes related to cachexia.<br><br>RECENT FINDINGS: Dysbiosis, an imbalance in gut microbiota, has been associated with cancer cachexia through pathways involving muscle wasting, inflammation, and gut barrier dysfunction. Interventions targeting gut microbiota, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have shown promising results in managing this syndrome in animal models. However, evidence in humans is currently limited.<br><br>SUMMARY: Mechanisms linking gut microbiota and cancer cachexia need to be further explored, and additional human research is necessary to evaluate the appropriate dosages, safety, and long-term outcomes of prebiotic and probiotic use in microbiota management for cancer cachexia.}, }
@article {pmid37386523, year = {2023}, author = {Zhou, M and Fan, Y and Xu, L and Yu, Z and Wang, S and Xu, H and Zhang, J and Zhang, L and Liu, W and Wu, L and Yu, J and Yao, H and Wang, J and Gao, R}, title = {Microbiome and tryptophan metabolomics analysis in adolescent depression: roles of the gut microbiota in the regulation of tryptophan-derived neurotransmitters and behaviors in human and mice.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {145}, pmid = {37386523}, issn = {2049-2618}, mesh = {Humans ; Adolescent ; Animals ; Mice ; *Gastrointestinal Microbiome ; Tryptophan ; Kynurenine ; Depression ; Quinolinic Acid ; Serotonin ; Sertraline ; *Microbiota ; Metabolomics ; }, abstract = {BACKGROUND: Adolescent depression is becoming one of the major public health concerns, because of its increased prevalence and risk of significant functional impairment and suicidality. Clinical depression commonly emerges in adolescence; therefore, the prevention and intervention of depression at this stage is crucial. Recent evidence supports the importance of the gut microbiota (GM) in the modulation of multiple functions associated with depression through the gut-brain axis (GBA). However, the underlying mechanisms remain poorly understood. Therefore, in the current study, we aimed to screen the microbiota out from healthy and depressive adolescents, delineate the association of the targeted microbiota and the adolescent depression, address the salutary effects of the targeted microbiota on anti-depressive behaviors in mice involving the metabolism of the tryptophan (Trp)-derived neurotransmitters along the GBA.<br><br>RESULTS: Here, we found the gut microbiota from healthy adolescent volunteers, first diagnosis patients of adolescent depression, and sertraline interveners after first diagnosis displayed significant difference, the relative abundance of Faecalibacterium, Roseburia, Collinsella, Blautia, Phascolarctobacterium, Lachnospiraceae-unclassified decreased in adolescent depressive patients, while restored after sertraline treatment. Of note, the Roseburia abundance exhibited a high efficiency in predicting adolescent depression. Intriguingly, transplantation of the fecal microbiota from healthy adolescent volunteers to the chronic restraint stress (CRS)-induced adolescent depressed mice significantly ameliorated mouse depressive behaviors, in which the Roseburia exerted critical roles, since its effective colonization in the mouse colon resulted in remarkably increased 5-HT level and reciprocally decreased kynurenine (Kyn) toxic metabolites quinolinic acid (Quin) and 3-hydroxykynurenine (3-HK) levels in both the mouse brain and colon. The specific roles of the Roseburia were further validated by the target bacteria transplantation mouse model, Roseburia intestinalis (Ri.) was gavaged to mice and importantly, it dramatically ameliorated CRS-induced mouse depressive behaviors, increased 5-HT levels in the brain and colon via promoting tryptophan hydroxylase-2 (TPH2) or -1 (TPH1) expression. Reciprocally, Ri. markedly restrained the limit-step enzyme responsible for kynurenine (indoleamine2,3-dioxygenase 1, IDO1) and quinolinic acid (3-hydroxyanthranilic acid 3,4-dioxygenase, 3HAO) generation, thereby decreased Kyn and Quin levels. Additionally, Ri. administration exerted a pivotal role in the protection of CRS-induced synaptic loss, microglial activation, and astrocyte maintenance.<br><br>CONCLUSIONS: This study is the first to delineate the beneficial effects of Ri. on adolescent depression by balancing Trp-derived neurotransmitter metabolism and improving synaptogenesis and glial maintenance, which may yield novel insights into the microbial markers and therapeutic strategies of GBA in adolescent depression. Video Abstract.}, }
@article {pmid37386288, year = {2023}, author = {Cozzi, G and Scagnellato, L and Lorenzin, M and Savarino, E and Zingone, F and Ometto, F and Favero, M and Doria, A and Vavricka, SR and Ramonda, R}, title = {Spondyloarthritis with inflammatory bowel disease: the latest on biologic and targeted therapies.}, journal = {Nature reviews. Rheumatology}, volume = {19}, number = {8}, pages = {503-518}, pmid = {37386288}, issn = {1759-4804}, mesh = {Humans ; Quality of Life ; *Spondylarthritis/complications ; *Inflammatory Bowel Diseases/complications ; Tumor Necrosis Factor Inhibitors/therapeutic use ; *Biological Products/therapeutic use ; }, abstract = {Spondyloarthritis (SpA) encompasses a heterogeneous group of chronic inflammatory diseases that can affect both axial and peripheral joints, tendons and entheses. Among the extra-articular manifestations, inflammatory bowel disease (IBD) is associated with considerable morbidity and effects on quality of life. In everyday clinical practice, treatment of these conditions requires a close collaboration between gastroenterologists and rheumatologists to enable early detection of joint and intestinal manifestations during follow-up and to choose the most effective therapeutic regimen, implementing precision medicine for each patient's subtype of SpA and IBD. The biggest issue in this field is the dearth of drugs that are approved for both diseases, as only TNF inhibitors are currently approved for the treatment of full-spectrum SpA-IBD. Janus tyrosine kinase inhibitors are among the most promising drugs for the treatment of peripheral and axial SpA, as well as for intestinal manifestations. Other therapies such as inhibitors of IL-23 and IL-17, phosphodiesterase 4 inhibitor, α4β7 integrin blockers and faecal microbiota transplantation seem to only be able to control some disease domains, or require further studies. Given the growing interest in the development of novel drugs to treat both conditions, it is important to understand the current state of the art and the unmet needs in the management of SpA-IBD.}, }
@article {pmid37384665, year = {2023}, author = {Galpérine, T and Engelmann, I and Hantz, S and Postil, D and Dewilde, A and Deplanque, D and Martin, R and Labreuche, J and Lazrek, M and Somers, S and Ribot, E and Alain, S}, title = {Cytomegalovirus in donors for fecal microbiota transplantation, the phantom menace?.}, journal = {PloS one}, volume = {18}, number = {6}, pages = {e0287847}, pmid = {37384665}, issn = {1932-6203}, mesh = {Humans ; *Fecal Microbiota Transplantation ; Cytomegalovirus ; Cross-Sectional Studies ; Prospective Studies ; Antibodies, Viral ; *Cytomegalovirus Infections/diagnosis/therapy ; Immunoglobulin M ; }, abstract = {BACKGROUND: Fecal Microbiota Transplantation (FMT) has become the preferred treatment for recurrent Clostridioides difficile Infections (CDI). However, donor screening is a complex process that varies between countries. The primary objective of screening is to prevent the transfer of potential pathogens from the donor to the recipient via feces. Many guidelines recommend Cytomegalovirus (CMV) testing as part of donor screening, but is the risk of CMV transmission well supported by evidence?<br><br>MATERIALS/METHODS: A French prospective cross-sectional multicenter single-arm study estimated the frequency of detection of CMV in the stool of voluntary healthy donors selected for FMT. All preselected donors were tested for CMV antibodies in blood, and if positive, CMV DNA PCR was performed on whole blood and stool. For samples CMV positive in stool PCR, or case of serological markers positive for IgM, we planned isolation of CMV in cell culture.<br><br>RESULTS: From June 1, 2016, to July 31, 2017, 500 healthy donors (250 per center) were recruited and 483 included. Of these, 301 were CMV seronegative, and 182 tested positive for CMV IgM and/or IgG. Stool CMV PCR was performed in 162 donors. In two cases, the initial analysis was positive, but below the limit of quantification. Repeated PCR tests using Siemens and Altostar assays were negative. No infectious CMV could be detected in cell culture of these two samples and in the stool of 6 CMV IgM-positive donors.<br><br>CONCLUSIONS: Our study shows that healthy volunteers with positive CMV serology do not shed CMV DNA in their stool, as detected by PCR or cell culture. This study provides another argument to remove CMV screening for FMT donors.}, }
@article {pmid37384590, year = {2023}, author = {Sjöland, W and Wahlström, A and Makki, K and Schöler, M and Molinaro, A and Olsson, L and Greiner, TU and Caesar, R and de Boer, JF and Kuipers, F and Bäckhed, F and Marschall, HU}, title = {Absence of gut microbiota reduces neonatal survival and exacerbates liver disease in Cyp2c70-deficient mice with a human-like bile acid composition.}, journal = {Clinical science (London, England : 1979)}, volume = {137}, number = {13}, pages = {995-1011}, pmid = {37384590}, issn = {1470-8736}, mesh = {Animals ; Female ; Male ; Mice ; Animals, Newborn ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome ; *Liver Diseases/metabolism/mortality ; Survival Analysis ; Mice, Knockout ; }, abstract = {Mice with deletion of Cyp2c70 have a human-like bile acid composition, display age- and sex-dependent signs of hepatobiliary disease and can be used as a model to study interactions between bile acids and the gut microbiota in cholestatic liver disease. In the present study, we rederived Cyp2c70-/- mice as germ-free (GF) and colonized them with a human or a mouse microbiota to investigate whether the presence of a microbiota can be protective in cholangiopathic liver disease associated with Cyp2c70-deficiency. GF Cyp2c70-/- mice showed reduced neonatal survival, liver fibrosis, and distinct cholangiocyte proliferation. Colonization of germ-free breeding pairs with a human or a mouse microbiota normalized neonatal survival of the offspring, and particularly colonization with mouse microbiota from a conventionally raised mouse improved the liver phenotype at 6-10 weeks of age. The improved liver phenotype in conventionalized (CD) Cyp2c70-/- mice was associated with increased levels of tauro-ursodeoxycholic acid (TUDCA) and UDCA, resulting in a more hydrophilic bile acid profile compared with GF and humanized Cyp2c70-/- mice. The hydrophobicity index of biliary bile acids of CD Cyp2c70-/- mice was associated with changes in gut microbiota, liver weight, liver transaminases, and liver fibrosis. Hence, our results indicate that neonatal survival of Cyp2c70-/- mice seems to depend on the establishment of a gut microbiota at birth, and the improved liver phenotype in CD Cyp2c70-/- mice may be mediated by a larger proportion of TUDCA/UDCA in the circulating bile acid pool and/or by the presence of specific bacteria.}, }
@article {pmid37384524, year = {2023}, author = {Bao, Z and Guo, C and Chen, Y and Li, C and Lei, T and Zhou, S and Qi, D and Xiang, Z}, title = {Fatty acid metabolization and insulin regulation prevent liver injury from lipid accumulation in Himalayan marmots.}, journal = {Cell reports}, volume = {42}, number = {7}, pages = {112718}, doi = {10.1016/j.celrep.2023.112718}, pmid = {37384524}, issn = {2211-1247}, mesh = {Animals ; Marmota/genetics ; Insulin ; Fatty Acids ; *Fatty Liver ; *Hibernation/physiology ; }, abstract = {Fat storage and weight gain are dominant traits for hibernating mammals. However, excessive fat accumulation may cause liver damage. Here, we explore the lipid accumulation and metabolic processes of the Himalayan marmot (Marmota himalayana), a hibernating rodent species. We find that the unsaturated fatty acid (UFA) content in food was consistent with a large increase in the body mass of Himalayan marmots. Metagenomic analysis shows that Firmicutes Bacterium CAG:110 plays a synergistic role by synthesizing UFAs, which is demonstrated by fecal transplantation experiments, indicating that the gut microbiome promotes fat storage in Himalayan marmots for hibernation. Microscopic examination results indicate that the risk of fatty liver appears at maximum weight; however, liver function is not affected. Upregulations of UFA catabolism and insulin-like growth factor binding protein genes provide an entry point for avoiding liver injury.}, }
@article {pmid37382445, year = {2023}, author = {Joubert, M and André, M and Barnich, N and Billard, E}, title = {Microbiome and Behçet's disease: a systematic review.}, journal = {Clinical and experimental rheumatology}, volume = {41}, number = {10}, pages = {2093-2104}, doi = {10.55563/clinexprheumatol/zbt4gx}, pmid = {37382445}, issn = {0392-856X}, mesh = {Humans ; Animals ; Mice ; *Behcet Syndrome/diagnosis ; Dysbiosis ; Epigenesis, Genetic ; *Uveitis ; *Microbiota ; Bacteria ; }, abstract = {The aim of this review was to describe the changes in the microbiota of patients with Behçet's disease (BD) and the mechanisms involved in the relationship between the microbiome and immunity in BD. A systematic search for relevant articles was made on PubMed and the Cochrane Library database using the following terms: "microbiota AND Behçet's disease" or "microbiome AND Behçet's disease". Sixteen articles were included in a qualitative synthesis. This systematic review on the microbiome and Behçet's disease underlines the presence of gut dysbiosis in BD patients. This dysbiosis is marked by (i) a decrease in butyrate-producing bacteria, which could affect T cell differentiation and epigenetic regulation of immune-related genes, (ii) a modification of tryptophan-metabolising bacteria, which could be linked to dysregulated IL-22 secretion, and (iii) a decrease in bacteria known to have anti-inflammatory properties. Regarding oral microbiota, this review underlines the possible role of Streptococcus sanguinis through molecular mimicry and NETosis. Clinical studies of BD have shown that (i) need for dentistry is associated with a more severe course in BD, and (ii) antibiotic-supplemented mouthwash reduces pain and ulcers. Fecal transplantation of BD patients' microbiota into mouse models led to decreased SCFA production, neutrophil activation, and Th1/Th17 responses.Recipient mice showed exacerbated experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE). In Herpes Virus Simplex-1 (HSV-1) infected mice mimicking BD, administration of butyrateproducing bacteria improved symptoms and immune variables. The microbiome may thus be involved in BD through immunity regulation and epigenetic modifications.}, }
@article {pmid37382423, year = {2023}, author = {Habibi, S and Rashidi, A}, title = {Fecal microbiota transplantation in hematopoietic cell transplant and cellular therapy recipients: lessons learned and the path forward.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2229567}, pmid = {37382423}, issn = {1949-0984}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/prevention &amp; control ; Dysbiosis/therapy ; }, abstract = {Disruptions to the gut microbiota have been associated with adverse outcomes including graft-versus-host disease, infections, and mortality after hematopoietic cell transplantation and cellular therapy. Evidence for causal links is accumulating, thus supporting therapeutic interventions targeting the microbiota with the goal of preventing and treating adverse outcomes. One such intervention is fecal microbiota transplantation (FMT) by which an entire community of gut microbiota is transferred to the patient with dysbiosis. As this approach in transplant and cellular therapy recipients is still in its infancy, no best approach has been defined and many open questions need to be addressed before FMT becomes a standard treatment. In this review, we highlight microbiota-outcome associations with the highest level of evidence, provide an overview of the main FMT trials, and suggest some paths forward.}, }
@article {pmid37381833, year = {2023}, author = {Lan, Y and Wang, D and He, J and Yang, H and Hou, Y and Di, W and Wang, H and Luo, X and Wei, L}, title = {The gut microbiome and metabolome in kidney transplant recipients with normal and moderately decreased kidney function.}, journal = {Renal failure}, volume = {45}, number = {1}, pages = {2228419}, pmid = {37381833}, issn = {1525-6049}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Kidney Transplantation ; Metabolome ; Amino Acids ; Kidney ; }, abstract = {BACKGROUND: The kidney transplant recipients (KTRs) were diagnosed with Chronic Kidney Disease after transplantation (CKD-T). CKD-T can be affected by the microbial composition and metabolites. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of CKD-T.<br><br>METHODS: We collected 100 fecal samples of KTRs and divided them into two groups according to the stage progression of CKD-T. Among them, 55 samples were analyzed by Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of KTRs were comprehensively characterized.<br><br>RESULTS: As well as significant differences in gut microbiome diversity between the CKD G1-2T group and CKD G3T group. Eight flora including Akkermansia were found to be enriched in CKD G3T group. As compared with CKD G1-2T group, the relative abundance of some amino acid metabolism, glycerophospholipid metabolism, amino acid biosynthesis, carbohydrate metabolism and purine metabolism in CKD G3T group were differential expressed significantly. In addition, fecal metabolome analysis indicated that CKD G3T group had a unique metabolite distribution characteristic. Two differentially expressed metabolites, N-acetylornithine and 5-deoxy-5'-(Methylthio) Adenosine, were highly correlated with serum creatinine, eGFR and cystatin C. The enrichment of gut microbial function in CKD-T is correlated with the expression of gut metabolites.<br><br>CONCLUSION: Gut microbiome and metabolites in the progression of CKD-T display some unique distribution and expression characteristics. The composition of the gut microbiome and their metabolites appears to be different between patients with CKD G3T and those with CKD G1-2T.}, }
@article {pmid37380586, year = {2023}, author = {Lee, DH and Jee, JJ and Lee, YS and Kim, DY and Bang, JY and Lee, HW and Koh, H and Bae, SH}, title = {Fecal microbiota transplantation improves hepatic fibro-inflammation via regulating oxidative stress in experimental NASH.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {55}, number = {11}, pages = {1521-1532}, doi = {10.1016/j.dld.2023.06.015}, pmid = {37380586}, issn = {1878-3562}, mesh = {Humans ; Animals ; Mice ; *Non-alcoholic Fatty Liver Disease/therapy ; Fecal Microbiota Transplantation ; Oxidative Stress ; Inflammation/therapy/pathology ; }, abstract = {Nonalcoholic steatohepatitis (NASH) is associated with imbalance of gut microbiome, indicating participation of gut environment in hepatic health status. Therefore, modulating gut environment via fecal microbiota transplantation (FMT) is a promising therapeutic procedure for NASH patients. However, the effect and mechanism of the FMT remains largely unknown. Here, we investigated the gut-liver axis to understand the FMT-mediated hepatic improvement in NASH. Feces from specific pathogen free mice were infused allogeneically into gastrointestinal tract of mice fed with high fat, high cholesterol and fructose (HFHCF), resulting in suppressing hepatic pathogenic events, featured by decreasing inflammatory and fibrotic mediators. The FMT elevated NF-E2-related factor 2 (NRF2), a key transcription factor that regulates antioxidant enzymes, in livers. The HFHCF-induced NASH increased intestinal permeability with abundant Facklamia and Aerococcus, an imbalanced gut environment that was significantly improved by the FMT, characterized with restoration of intestinal barrier function and an enrichment of Clostridium. Notably, the gut environment created by FMT was inferred to produce metabolites from the aromatic biogenic amine degradation pathway, specifically 4-hydroxyphenylacetic acid (4-HPA), which is known to ameliorate liver injury. We suggest that gut-derived molecules, related to hepatic improvement such as 4-HPA are the potential therapeutic agents for preventing and treating NASH.}, }
@article {pmid37379664, year = {2023}, author = {Zhang, Y and Li, M and Pu, Z and Chi, X and Yang, J}, title = {Multi-omics data reveals the disturbance of glycerophospholipid metabolism and linoleic acid metabolism caused by disordered gut microbiota in PM2.5 gastrointestinal exposed rats.}, journal = {Ecotoxicology and environmental safety}, volume = {262}, number = {}, pages = {115182}, doi = {10.1016/j.ecoenv.2023.115182}, pmid = {37379664}, issn = {1090-2414}, abstract = {The relationships between fine particulate matter (PM2.5) exposure and health effects are complex and incompletely understood. Evidence suggests that PM2.5 exposure alters gut microbiota composition and metabolites, but the connections between these changes remain unclear. The aim of our study was to investigate how gut microbiota are involved in the systemic metabolic changes following PM2.5 gastrointestinal exposure. We used multi-omics approaches, including 16S rRNA sequencing and serum metabolomics, to identify alterations in gut microbes and metabolites of PM2.5-exposed rats. We then explored correlations between perturbed gut microbiota and metabolic changes, and conducted pathway analyses to determine critical metabolic pathways impacted by PM2.5 exposure. To verify links between gut microbiome and metabolome disruptions, we performed fecal microbiota transplantation (FMT) experiment. A total of 30 differential gut microbe taxa were identified between PM2.5 and control groups, primarily in Firmicutes, Acidobacteria, and Proteobacteria phyla. We also identified 30 differential metabolites, including glycerophospholipids, fatty acyls, amino acids and others. Pathway analysis revealed disruptions in glycerophospholipid metabolism, steroid hormone biosynthesis, and linoleic acid metabolism. Through FMT, we confirmed PM2.5 altered phosphatidylcholine and linoleic acid metabolism by changing specific gut bacteria. Our results suggest that PM2.5 gastrointestinal exposure triggers systemic metabolic changes by disrupting the gut microbiome, especially glycerophospholipid and linoleic acid metabolism pathways.}, }
@article {pmid37377226, year = {2023}, author = {Dörk, R and Pelczar, P and Shiri, AM and Volmari, A and Zierz, E and Giannou, A and Böttcher, M and Bosurgi, L and Huber, S and Manthey, CF}, title = {Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility.}, journal = {Journal of Crohn's &amp; colitis}, volume = {17}, number = {11}, pages = {1858-1869}, doi = {10.1093/ecco-jcc/jjad103}, pmid = {37377226}, issn = {1876-4479}, support = {MA-4980/4-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; *Colitis/pathology ; *Inflammatory Bowel Diseases/complications ; Myeloid Cells/pathology ; Anti-Inflammatory Agents/adverse effects ; Dextran Sulfate ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND AND AIMS: The incidence of inflammatory bowel diseases [IBD] is steadily increasing, and thus the identification of new targets to improve therapy is a major goal. Growth factors of the PDGF family and their receptors are expressed early in intestinal development and are found in mononuclear cells and macrophages in adult tissues. Macrophages play a distinct role in the pathogenesis of IBD since their function is crucial to maintaining tolerance.<br><br>METHODS: We aimed to study the role of myeloid expression of PDGFR-&#x3b1; in mediating intestinal homeostasis in mouse IBD and infectious models.<br><br>RESULTS: Our results show that loss of myeloid PDGFR-&#x3b1; increases susceptibility to dextran saline sulphate-induced colitis. Accordingly, LysM-PDGFR-&#x3b1;-/- mice showed higher colitis scores, and reduced levels of anti-inflammatory macrophages compared to control mice. This effect was mediated via a pro-colitogenic microbiota, which developed in the absence of myeloid PDGFR-&#x3b1; and caused increased colitis susceptibility in gnotobiotic mice upon faecal microbiota transplantation compared to controls. Furthermore, LysM-PDGFR-&#x3b1;-/- mice had a leaky gut, accompanied by impaired phagocytosis, resulting in a severe barrier defect.<br><br>CONCLUSIONS: Taken together, our results indicate a protective role for myeloid PDGFR-&#x3b1; in maintaining gut homeostasis by promoting a protective intestinal microbiota and providing an anti-inflammatory macrophage phenotype.}, }
@article {pmid37376687, year = {2023}, author = {Songtanin, B and Molehin, AJ and Brittan, K and Manatsathit, W and Nugent, K}, title = {Hepatitis E Virus Infections: Epidemiology, Genetic Diversity, and Clinical Considerations.}, journal = {Viruses}, volume = {15}, number = {6}, pages = {}, pmid = {37376687}, issn = {1999-4915}, mesh = {Animals ; Humans ; *Hepatitis E virus/genetics ; Molecular Epidemiology ; *Hepatitis E ; Zoonoses/epidemiology ; Hepatitis, Chronic ; Genotype ; }, abstract = {According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are four main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans via undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection, and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.}, }
@article {pmid37375456, year = {2023}, author = {Boicean, A and Bratu, D and Bacila, C and Tanasescu, C and Fleacă, RS and Mohor, CI and Comaniciu, A and Băluță, T and Roman, MD and Chicea, R and Cristian, AN and Hasegan, A and Birsan, S and Dura, H and Mohor, CI}, title = {Therapeutic Perspectives for Microbiota Transplantation in Digestive Diseases and Neoplasia-A Literature Review.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {6}, pages = {}, pmid = {37375456}, issn = {2076-0817}, support = {contract no. 28PFE/30.12.2021//Ministerul Cercet&#x103;rii &#x219;i Inov&#x103;rii/ ; }, abstract = {In a mutually beneficial connection with its host, the gut microbiota affects the host's nutrition, immunity, and metabolism. An increasing number of studies have shown links between certain types of disease and gut dysbiosis or specific microorganisms. Fecal microbiota transplantation (FMT) is strongly advised for the treatment of recurrent or resistant Clostridium difficile infection (CDI) due to its outstanding clinical effectiveness against CDI. The therapeutic potential of FMT for other disorders, particularly inflammatory bowel diseases and malignancies, is currently gaining more and more attention. We summarized the most recent preclinical and clinical evidence to show the promise of FMT in the management of cancer as well as complications related to cancer treatment after reviewing the most recent research on the gut microbiota and its relationship to cancer.}, }
@article {pmid37374979, year = {2023}, author = {Inchingolo, AM and Patano, A and Piras, F and Mancini, A and Inchingolo, AD and Paduanelli, G and Inchingolo, F and Palermo, A and Dipalma, G and Malcangi, G}, title = {Interconnection between Microbiota-Gut-Brain Axis and Autism Spectrum Disorder Comparing Therapeutic Options: A Scoping Review.}, journal = {Microorganisms}, volume = {11}, number = {6}, pages = {}, pmid = {37374979}, issn = {2076-2607}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a group of neurodevelopmental illnesses characterized by difficulty in social communication, social interaction, and repetitive behaviors. These clinical diagnostic criteria can be seen in children as early as one year old and are commonly associated with long-term difficulties. ASD is connected with a higher frequency of various medical diseases such as gastrointestinal complaints, seizures, anxiety, interrupted sleep, and immunological dysfunction, in addition to the range of developmental abnormalities listed.<br><br>METHODS: From 1 January 2013 to 28 February 2023, we searched PubMed, Scopus and Web of Science for English-language papers that matched our topic. The following Boolean keywords were utilized in the search approach: "autism" AND "microbiota". After deleting duplicates, a total of 2370 publications were found from the databases, yielding 1222 articles. (1148). Nine hundred and eighty-eight items were excluded after their titles and abstracts were scrutinized. The method resulted in the removal of 174 items for being off-topic. The final 18 articles for qualitative analysis are included in the evaluation.<br><br>CONCLUSION: The findings of this extensive study revealed that probiotics, prebiotics, their combination as synbiotics, fecal microbiota transplantation, and microbiota transfer therapy may benefit ASD patients suffering from both gastrointestinal and central nervous system symptoms.}, }
@article {pmid37374933, year = {2023}, author = {Aljuraiban, GS and Alfhili, MA and Aldhwayan, MM and Aljazairy, EA and Al-Musharaf, S}, title = {Shared and Distinct Gut Microbial Profiles in Saudi Women with Metabolically Healthy and Unhealthy Obesity.}, journal = {Microorganisms}, volume = {11}, number = {6}, pages = {}, pmid = {37374933}, issn = {2076-2607}, support = {IFKSUDR_H137//The authors extend their appreciation to the Deputyship for Research &amp; Innovation, "Ministry of Education" in Saudi Arabia for funding this research work through the Directed Research Projects Fund number/ ; }, abstract = {Mounting evidence suggests a pivotal role for the gut microbiome in energy disequilibrium characteristic of obesity. The clinical utility of microbial profiling for the distinction between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) remains ill-defined. We aim to probe microbial composition and diversity in young adult Saudi females with MHO and MUO. This observational study included anthropometric and biochemical measurements and shotgun sequencing of stool DNA for 92 subjects. α- and β-diversity metrics were calculated to determine the richness and variability in microbial communities, respectively. Results showed that Bacteroides and Bifidobacterium merycicum were less abundant in MUO compared to healthy and MHO groups. BMI was negatively correlated with B. adolescentis, B. longum, and Actinobacteria in MHO, while being positively correlated with Bacteroides thetaiotaomicron in both MHO and MUO. Positive correlations between waist circumference and B. merycicum and B. thetaiotaomicron were observed in MHO and MUO, respectively. Compared to MHO and MUO groups, higher α-diversity was detected in healthy individuals who also had higher β-diversity compared to those with MHO. We conclude that modulation of the gut microbiome cohorts through prebiotics, probiotics, and fecal microbiota transplantation may be a promising preventive and therapeutic approach to obesity-associated disease.}, }
@article {pmid37374929, year = {2023}, author = {Tuniyazi, M and Zhang, N}, title = {Possible Therapeutic Mechanisms and Future Perspectives of Vaginal Microbiota Transplantation.}, journal = {Microorganisms}, volume = {11}, number = {6}, pages = {}, pmid = {37374929}, issn = {2076-2607}, abstract = {Microbial communities inhabiting the human body play a crucial role in protecting the host against pathogens and inflammation. Disruptions to the microbial composition can lead to various health issues. Microbial transfer therapy (MTT) has emerged as a potential treatment option to address such issues. Fecal microbiota transplantation (FMT) is the most widely used form of MTT and has been successful in treating several diseases. Another form of MTT is vaginal microbiota transplantation (VMT), which involves transferring vaginal microbiota from a healthy female donor to a diseased patient's vaginal cavity with the goal of restoring normal vaginal microbial composition. However, VMT has not been extensively studied due to safety concerns and a lack of research. This paper explores the therapeutic mechanisms of VMT and discusses future perspectives. Further research is necessary to advance the clinical applications and techniques of VMT.}, }
@article {pmid37373260, year = {2023}, author = {Kim, YS and Lee, HAR and Lee, MJ and Park, YJ and Mun, S and Yune, CJ and Chung, TN and Bae, J and Kim, MJ and Choi, YS and Kim, K}, title = {The Effects of Mitochondrial Transplantation on Sepsis Depend on the Type of Cell from Which They Are Isolated.}, journal = {International journal of molecular sciences}, volume = {24}, number = {12}, pages = {}, pmid = {37373260}, issn = {1422-0067}, support = {2020R1A2C3004508//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Lipopolysaccharides/metabolism ; Mitochondria/metabolism ; *Sepsis/metabolism ; Inflammation/metabolism ; Monocytes/metabolism ; }, abstract = {Previously, we have shown that mitochondrial transplantation in the sepsis model has immune modulatory effects. The mitochondrial function could have different characteristics dependent on cell types. Here, we investigated whether the effects of mitochondrial transplantation on the sepsis model could be different depending on the cell type, from which mitochondria were isolated. We isolated mitochondria from L6 muscle cells, clone 9 liver cells and mesenchymal stem cells (MSC). We tested the effects of mitochondrial transplantation using in vitro and in vivo sepsis models. We used the LPS stimulation of THP-1 cell, a monocyte cell line, as an in vitro model. First, we observed changes in mitochondrial function in the mitochondria-transplanted cells. Second, we compared the anti-inflammatory effects of mitochondrial transplantation. Third, we investigated the immune-enhancing effects using the endotoxin tolerance model. In the in vivo polymicrobial fecal slurry sepsis model, we examined the survival and biochemical effects of each type of mitochondrial transplantation. In the in vitro LPS model, mitochondrial transplantation with each cell type improved mitochondrial function, as measured by oxygen consumption. Among the three cell types, L6-mitochondrial transplantation significantly enhanced mitochondrial function. Mitochondrial transplantation with each cell type reduced hyper-inflammation in the acute phase of in vitro LPS model. It also enhanced immune function during the late immune suppression phase, as shown by endotoxin tolerance. These functions were not significantly different between the three cell types of origin for mitochondrial transplantation. However, only L6-mitochondrial transplantation significantly improved survival compared to the control in the polymicrobial intraabdominal sepsis model. The effects of mitochondria transplantation on both in vitro and in vivo sepsis models differed depending on the cell types of origin for mitochondria. L6-mitochondrial transplantation might be more beneficial in the sepsis model.}, }
@article {pmid37371254, year = {2023}, author = {Mandato, C and Colucci, A and Lanzillo, R and Staiano, A and Scarpato, E and Schiavo, L and Operto, FF and Serra, MR and Di Monaco, C and Napoli, JS and Massa, G and Vajro, P}, title = {Multiple Sclerosis-Related Dietary and Nutritional Issues: An Updated Scoping Review with a Focus on Pediatrics.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {37371254}, issn = {2227-9067}, abstract = {PURPOSE: Lifestyle/dietetic habits play an important role in the development and progression of multiple sclerosis (MS) disease. Here, we examine the basic pathomechanisms underlying intestinal and brain barrier modifications in MS and consider diets and dietary supplementations proposed over time to complement pharmacological therapies for improving disease outcome both in adults and in children.<br><br>METHODS: Scoping literature search about evidence-based findings in MS-related gut-brain axis (GBA) pathophysiology and nutritional issues at all ages.<br><br>FINDINGS: Data show that (1) no universal best diet exists, (2) healthy/balanced diets are, however, necessary to safeguard the adequate intake of all essential nutrients, (3) diets with high intakes of fruits, vegetables, whole grains, and lean proteins that limit processed foods, sugar, and saturated fat appear beneficial for their antioxidant and anti-inflammatory properties and their ability to shape a gut microbiota that respects the gut and brain barriers, (4) obesity may trigger MS onset and/or its less favorable course, especially in pediatric-onset MS. Vitamin D and polyunsaturated fatty acids are the most studied supplements for reducing MS-associated inflammation.<br><br>CONCLUSIONS: Pending results from other and/or newer approaches targeting the GBA (e.g., pre- and probiotics, engineered probiotics, fecal-microbiota transplantation), accurate counseling in choosing adequate diet and maintaining physical activity remains recommended for MS prevention and management both in adults and children.}, }
@article {pmid37370508, year = {2023}, author = {Arnaud, EA and Gardiner, GE and Lawlor, PG}, title = {Selected Nutrition and Management Strategies in Suckling Pigs to Improve Post-Weaning Outcomes.}, journal = {Animals : an open access journal from MDPI}, volume = {13}, number = {12}, pages = {}, pmid = {37370508}, issn = {2076-2615}, support = {2019R518//Irish Department of Agriculture, Food and the Marine/ ; }, abstract = {Weaning is a critical period in a pig's life. Piglets are confronted with abrupt changes to their physical and social environment, as well as management and nutritional changes. Weaning has always been associated with a growth check and is frequently accompanied by post-weaning diarrhoea in piglets. However, rapid increases in litter size in the last decade have increased within-litter piglet weight variation, with piglets now generally lighter at weaning, making the challenges associated with weaning even greater. Many interventions can be employed during the suckling period to ease the weaning transition for piglets. Pre-weaning strategies such as supervised farrowing (assistance with suckling and oxytocin provision), the provision of pain relief to sows around farrowing, split-suckling, early oral supplementation with glucose, bovine colostrum, faecal microbiota transplantation, feed additives and solid and liquid creep feeding (milk and liquid feed) have all been investigated. The objective of these strategies is to stimulate earlier maturation of the digestive tract, improve immunity, reduce latency to the first feed post-weaning and increase early post-weaning feed intake and growth. This review focuses in particular on: (1) pain relief provision to sows around farrowing, (2)split-suckling of piglets, (3) pre-weaning provision of supplementary milk and/or liquid feed, (4) other strategies to stimulate earlier enzyme production (e.g., enzyme supplementation), (5) other nutritional strategies to promote improved gut structure and function (e.g., L-glutamine supplementation), and (6) other strategies to modulate gut microbiota (e.g., probiotics and prebiotics). Correctly implementing these strategies can, not only increase post-weaning growth and reduce mortality, but also maximise lifetime growth in pigs.}, }
@article {pmid37370393, year = {2023}, author = {Roson-Calero, N and Ballesté-Delpierre, C and Fernández, J and Vila, J}, title = {Insights on Current Strategies to Decolonize the Gut from Multidrug-Resistant Bacteria: Pros and Cons.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {6}, pages = {}, pmid = {37370393}, issn = {2079-6382}, abstract = {In the last decades, we have witnessed a steady increase in infections caused by multidrug-resistant (MDR) bacteria. These infections are associated with higher morbidity and mortality. Several interventions should be taken to reduce the emergence and spread of MDR bacteria. The eradication of resistant pathogens colonizing specific human body sites that would likely cause further infection in other sites is one of the most conventional strategies. The objective of this narrative mini-review is to compile and discuss different strategies for the eradication of MDR bacteria from gut microbiota. Here, we analyse the prevalence of MDR bacteria in the community and the hospital and the clinical impact of gut microbiota colonisation with MDR bacteria. Then, several strategies to eliminate MDR bacteria from gut microbiota are described and include: (i) selective decontamination of the digestive tract (SDD) using a cocktail of antibiotics; (ii) the use of pre and probiotics; (iii) fecal microbiota transplantation; (iv) the use of specific phages; (v) engineered CRISPR-Cas Systems. This review intends to provide a state-of-the-art of the most relevant strategies to eradicate MDR bacteria from gut microbiota currently being investigated.}, }
@article {pmid37368219, year = {2024}, author = {Tripathi, PR and Srivastava, A}, title = {Approach to a Child with Chronic Diarrhea.}, journal = {Indian journal of pediatrics}, volume = {91}, number = {5}, pages = {472-480}, pmid = {37368219}, issn = {0973-7693}, mesh = {Infant, Newborn ; Child ; Adolescent ; Humans ; *Diarrhea/diagnosis ; *Colonoscopy/adverse effects ; Feces ; Physical Examination/adverse effects ; Chronic Disease ; }, abstract = {Chronic diarrhea in children is challenging both with regards to etiological diagnosis and for management. Etiology and pathophysiological mechanisms vary widely from neonates to adolescents. Congenital or genetic causes are more frequent in neonates, while infections, allergy and immune-mediated mechanisms are more frequent in childhood. A thorough history and proper physical examination are required to decide for further diagnostic evaluation. The approach to a child with chronic diarrhea should be age specific and based predominantly on the pathophysiological mechanism involved. The nature of the stool like watery, bloody or fatty (steatorrhea) can suggest the probable etiology and organ system involved. After routine tests, evaluation with specific serological tests, imaging, endoscopy (gastroscopy/colonoscopy), histopathology of intestinal mucosa, breath tests or radionuclide imaging may be required to make a definitive diagnosis. Genetic evaluation is important in congenital diarrheas, monogenic inflammatory bowel disease (IBD) and immunodeficiency disorders. Management is aimed at stabilization, nutritional support and etiology specific treatment. Specific therapy can be as simple as exclusion of specific nutrient or as complicated as small bowel transplant. Evaluation and management require expertise and thus patients need to be referred in a timely fashion. This will minimise morbidity including nutritional consequences and improve outcome.}, }
@article {pmid37366528, year = {2023}, author = {Scaglione, S and Gotta, F and Vay, D and Leli, C and Roveta, A and Maconi, A and Rocchetti, A}, title = {Rapid RT-PCR identification of SARS-CoV-2 in screening donors of fecal microbiota transplantation.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e17438}, pmid = {37366528}, issn = {2405-8440}, abstract = {Since its first appearance in late 2019 in Wuhan, China, severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2) has had a major impact on healthcare facilities around the world. Although in the past year, mass vaccination and the development of monoclonal antibody treatments have reduced the number of deaths and severe cases, the circulation of SARS-CoV-2 remains high. Over the past two years, diagnostics have played a crucial role in virus containment both in health care facilities and at the community level. For SARS-CoV-2 detection, the commonly used specimen type is the nasopharyngeal swab, although the virus can be identified in other matrices such as feces. Since fecal microbiota transplantation (FMT) assumes significant importance in the treatment of chronic gut infections and that feces may be a potential vehicle for transmission of SARS-CoV-2, in this study we have evaluated the performance of the rapid cartridge-based RT-PCR test STANDARD™ M10 SARS-CoV-2 (SD Biosensor Inc., Suwon, South Korea) using fecal samples. The results obtained indicates that STANDARD™ M10 SARS-CoV-2 can detect SARS-CoV-2 in stool samples even at low concentration. For this reason, STANDARD™ M10 SARS-CoV-2 could be used as reliable methods for the detection of SARS-CoV-2 in fecal samples and for the screening of FMT donors.}, }
@article {pmid37365109, year = {2023}, author = {Chu, HK and Ai, Y and Cheng, ZL and Yang, L and Hou, XH}, title = {Contribution of gut microbiota to drug-induced liver injury.}, journal = {Hepatobiliary &amp; pancreatic diseases international : HBPD INT}, volume = {22}, number = {5}, pages = {458-465}, doi = {10.1016/j.hbpd.2023.06.008}, pmid = {37365109}, issn = {1499-3872}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *Liver Diseases ; *Chemical and Drug Induced Liver Injury/etiology/therapy ; Fecal Microbiota Transplantation ; Dysbiosis ; *Probiotics/therapeutic use ; }, abstract = {Drug-induced liver injury (DILI) is caused by various drugs with complex pathogenesis, and diverse clinical and pathological phenotypes. Drugs damage the liver directly through drug hepatotoxicity, or indirectly through drug-mediated oxidative stress, immune injury and inflammatory insult, which eventually lead to hepatocyte necrosis. Recent studies have found that the composition, relative content and distribution of gut microbiota in patients and animal models of DILI have changed significantly. It has been confirmed that gut microbial dysbiosis brings about intestinal barrier destruction and microorganisms translocation, and the alteration of microbial metabolites may cause or aggravate DILI. In addition, antibiotics, probiotics, and fecal microbiota transplantation are all emerging as prospective therapeutic methods for DILI by regulating the gut microbiota. In this review, we discussed how the altered gut microbiota participates in DILI.}, }
@article {pmid37364760, year = {2024}, author = {Zhou, X and Zhang, X and Yu, J}, title = {Gut mycobiome in metabolic diseases: Mechanisms and clinical implication.}, journal = {Biomedical journal}, volume = {47}, number = {3}, pages = {100625}, pmid = {37364760}, issn = {2320-2890}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Mycobiome ; *Metabolic Diseases/microbiology ; Dysbiosis/microbiology ; Diabetes Mellitus, Type 2/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation/methods ; Non-alcoholic Fatty Liver Disease/microbiology ; Animals ; Fungi ; }, abstract = {Obesity, type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are three common metabolic diseases with high prevalence worldwide. Emerging evidence suggests that gut dysbiosis may influence the development of metabolic diseases, in which gut fungal microbiome (mycobiome) is actively involved. In this review, we summarize the studies exploring the composition changes of gut mycobiome in metabolic diseases and mechanisms by which fungi affect the development of metabolic diseases. The current mycobiome-based therapies, including probiotic fungi, fungal products, anti-fungal agents and fecal microbiota transplantation (FMT), and their implication in treating metabolic diseases are discussed. We highlight the unique role of gut mycobiome in metabolic diseases, providing perspectives for future research on gut mycobiome in metabolic diseases.}, }
@article {pmid37364420, year = {2023}, author = {Lan, T and Tang, T and Li, Y and Duan, Y and Yuan, Q and Liu, W and Ren, Y and Li, N and Liu, X and Zhang, Y and Li, X and Jin, G and Wang, S and Guo, J}, title = {FTZ polysaccharides ameliorate kidney injury in diabetic mice by regulating gut-kidney axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {118}, number = {}, pages = {154935}, doi = {10.1016/j.phymed.2023.154935}, pmid = {37364420}, issn = {1618-095X}, mesh = {Mice ; Animals ; *Diabetes Mellitus, Experimental ; Ecosystem ; RNA, Ribosomal, 16S ; Kidney ; Polysaccharides/pharmacology ; Inflammation ; }, abstract = {BACKGROUND: The Fufang-zhenzhu-tiaozhi formula (FTZ), a traditional Chinese medicine (TCM) commonly used to treat metabolic diseases, potentially impacts the microbial ecosystem. Increasing evidence suggests that polysaccharides, bioactive components of TCMs, have great potential on kinds of diseases such as DKD by regulating intestinal flora.<br><br>PURPOSE: This study aimed to investigate whether the polysaccharide components in FTZ (FTZPs) have beneficial effects in DKD mice via the gut-kidney axis.<br><br>STUDY DESIGN AND METHODS: The DKD model in mice was established by streptozotocin combined with a high-fat diet (STZ/HFD). Losartan was used as a positive control, and FTZPs were administered at doses of 100 and 300&#xa0;mg/kg daily. Renal histological changes were measured by H&amp;E and Masson staining. Western blotting, quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry were performed to analyze the effects of FTZPs on renal inflammation and fibrosis, which were further confirmed using RNA sequencing. Immunofluorescence was used to analyze the effects of FTZPs on colonic barrier function in DKD mice. Faecal microbiota transplantation (FMT) was used to evaluate the contribution of intestinal flora. 16S rRNA sequencing was utilized to analyze the composition of intestinal bacteria, and UPLC-QTOF-MS-based untargeted metabolomics was used to identify the metabolite profiles.<br><br>RESULTS: Treatment with FTZPs attenuated kidney injury, as indicated by the decreased urinary albumin/creatinine ratio and improved renal architecture. FTZPs downregulated the expression of renal genes associated with inflammation, fibrosis, and systematically blunted related pathways. FTZPs also restored the colonic mucosal barrier and increased the expression of tight junction proteins (E-cadherin). The FMT experiment confirmed the substantial contribution of the FTZPs-reshaped microbiota to relieving DKD symptoms. Moreover, FTZPs elevated the content of short-chain fatty acids (propionic acid and butanoic acid) and increased the level of the SCFAs transporter Slc22a19. Intestinal flora disorders caused by diabetes, including the growth of the genera Weissella, Enterococcus and Akkermansia, were inhibited by FTZPs treatment. Spearman's analysis revealed that these bacteria were positively correlated with indicators of renal damage.<br><br>CONCLUSION: These results show that oral administration of FTZPs, by altering SCFAs levels and the gut microbiome, is a therapeutic strategy for the treatment of DKD.}, }
@article {pmid37362944, year = {2023}, author = {Du, W and Wang, X and Hu, M and Hou, J and Du, Y and Si, W and Yang, L and Xu, L and Xu, Q}, title = {Modulating gastrointestinal microbiota to alleviate diarrhea in calves.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1181545}, pmid = {37362944}, issn = {1664-302X}, abstract = {The calf stage is a critical period for the development of heifers. Newborn calves have low gastrointestinal barrier function and immunity before weaning, making them highly susceptible to infection by various intestinal pathogens. Diarrhea in calves poses a significant threat to the health of young ruminants and may cause serious economic losses to livestock farms. Antibiotics are commonly used to treat diarrhea and promote calf growth, leading to bacterial resistance and increasing antibiotic residues in meat. Therefore, finding new technologies to improve the diarrhea of newborn calves is a challenge for livestock production and public health. The operation of the gut microbiota in the early stages after birth is crucial for optimizing immune function and body growth. Microbiota colonization of newborn animals is crucial for healthy development. Early intervention of the calf gastrointestinal microbiota, such as oral probiotics, fecal microbiota transplantation and rumen microbiota transplantation can effectively relieve calf diarrhea. This review focuses on the role and mechanisms of oral probiotics such as Lactobacillus, Bifidobacterium and Faecalibacterium in relieving calf diarrhea. The aim is to develop appropriate antibiotic alternatives to improve calf health in a sustainable and responsible manner, while addressing public health issues related to the use of antibiotics in livestock.}, }
@article {pmid37362402, year = {2023}, author = {Niyazi, D and Micheva, I and Dokova, K and Stoeva, T}, title = {Incidence, Risk Factors and Outcome of Bloodstream Infections in Patients After Hematopoietic Stem-Cell Transplantation: A Single Center Study.}, journal = {Indian journal of hematology &amp; blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion}, volume = {39}, number = {4}, pages = {1-5}, pmid = {37362402}, issn = {0971-4502}, abstract = {The bloodstream infections (BSIs) are among the most common infectious complications after hematopoietic stem-cell transplantation (HSCT), often associated with high mortality rates. The aim of this study was to evaluate the incidence, risk factors and outcome of BSIs in HSCT recipients from the Transplantation Center of the University Hospital in Varna, Bulgaria during the period January 2019-December 2021. The role of patient- and transplantation-related variables was studied as potential risk factors for BSIs and survival after HSCT. Seventy-four patients were included in the study. The cumulative incidence of BSIs was 35%. The mean period of BSI onset after HSCT was 8 days. The Gram-positive bacteria were more commonly isolated as causative agents (52.3%). The mortality rate 30 days after the diagnosis of BSI was 23%. Fecal colonization with multidrug-resistant (MDR) bacteria (p = 0.005) and pre-transplant BSI (p = 0.05) were associated with significantly increased risk for post-HSCT BSIs. The overall 4-month survival was 86.5%. A statistical significance was found between the type of the underlying disease (acute leukemia and lymphoma, p = 0.043), previous HSCT (p = 0.001) and 4-month survival. This study confirms that the fecal colonization with MDR bacteria before transplantation and pre-transplant BSIs are independent risk factors for the occurrence of BSI in the early period after HSCT. Pre- and posttransplant monitoring of the patient fecal colonization status with MDR organisms, could contribute considerably to the prevention and successful management of the infectious complications in patients after HSCT.}, }
@article {pmid37358099, year = {2022}, author = {Núñez, P and Quera, R and Von Muhlenbrock, C and Concha, A and Flores, K}, title = {[Fecal microbiota transplantation in an older patient with Clostridioides difficile recurrent infection. Report of one case].}, journal = {Revista medica de Chile}, volume = {150}, number = {10}, pages = {1396-1400}, doi = {10.4067/S0034-98872022001001396}, pmid = {37358099}, issn = {0717-6163}, mesh = {Aged ; Humans ; Male ; *Clostridioides difficile ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; *Reinfection/therapy ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection (CDI) is a major public health problem and responsible for significant morbidity and mortality. Eighty percent of CDIs occur in adults older than 65 years of age due to a decreased gastrointestinal microbial diversity, immunosenescence and frailty. Thus, the most reported risk factor for recurrent CDI is older age since nearly 60% of cases occur in individuals aged ≥ 65 years. Fecal microbiota transplantation (FMT) is a highly cost-effective alternative to antibiotic treatment for patients with recurrent CDI. We report a 75-year-old male with recurrent CDI, who received a FMT after several unsuccessful antimicrobial treatments. He had a satisfactory evolution after the procedure and remained without diarrhea during the ensuing five months.}, }
@article {pmid37357103, year = {2023}, author = {Marsool, MDM and Vora, N and Marsool, ADM and Pati, S and Narreddy, M and Patel, P and Gadam, S and Prajjwal, P}, title = {Ulcerative colitis: Addressing the manifestations, the role of fecal microbiota transplantation as a novel treatment option and other therapeutic updates.}, journal = {Disease-a-month : DM}, volume = {69}, number = {11}, pages = {101606}, doi = {10.1016/j.disamonth.2023.101606}, pmid = {37357103}, issn = {1557-8194}, mesh = {Humans ; *Colitis, Ulcerative/therapy/diagnosis ; Fecal Microbiota Transplantation/methods ; Feces ; Inflammation ; Treatment Outcome ; }, abstract = {The prevalence and incidence of Ulcerative Colitis (UC), a recurrent and remitting inflammatory condition, are rising. Any part of the colon may be affected, beginning with inflammation of the mucosa in the rectum and continuing proximally continuously. Bloody diarrhea, tenesmus, fecal urgency, and stomach pain are typical presenting symptoms. Many patients present with extraintestinal manifestations (EIMs) including musculoskeletal, ocular, renal, hepatobiliary, and dermatological presentation, among others. Most cases are treated with pharmacological therapy including mesalazine and glucocorticoids. Fecal microbiota transplantation (FMT) is a novel procedure that is increasingly being used to treat UC, however, its use yet remains controversial because of uncertain efficacy. FMT can lower gut permeability and consequently disease severity by boosting short-chain fatty acids production, helping in epithelial barrier integrity preservation. Upadacitinib (JAK Kinase inhibitor) is another newer treatment option, which is an FDA-approved drug that is being used to treat UC. This review article provides a comprehensive review of the EIMs of UC, the role of FMT along with various recent clinical trials pertaining to FMT as well as other diagnostic and therapeutic updates.}, }
@article {pmid37356750, year = {2023}, author = {Sharma, G and Biswas, SS and Mishra, J and Navik, U and Kandimalla, R and Reddy, PH and Bhatti, GK and Bhatti, JS}, title = {Gut microbiota dysbiosis and Huntington's disease: Exploring the gut-brain axis and novel microbiota-based interventions.}, journal = {Life sciences}, volume = {328}, number = {}, pages = {121882}, doi = {10.1016/j.lfs.2023.121882}, pmid = {37356750}, issn = {1879-0631}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Brain-Gut Axis ; Dysbiosis/therapy ; *Huntington Disease/therapy ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {Huntington's disease (HD) is a complex progressive neurodegenerative disorder affected by genetic, environmental, and metabolic factors contributing to its pathogenesis. Gut dysbiosis is termed as the alterations of intestinal microbial profile. Emerging research has highlighted the pivotal role of gut dysbiosis in HD, focusing on the gut-brain axis as a novel research parameter in science. This review article provides a comprehensive overview of gut microbiota dysbiosis and its relationship with HD and its pathogenesis along with the future challenges and opportunities. The focuses on the essential mechanisms which link gut dysbiosis to HD pathophysiology including neuroinflammation, immune system dysregulation, altered metabolites composition, and neurotransmitter imbalances. We also explored the impacts of gut dysbiosis on HD onset, severity, and symptoms such as cognitive decline, motor dysfunction, and psychiatric symptoms. Furthermore, we highlight recent advances in therapeutics including microbiota-based therapeutic approaches, including dietary interventions, prebiotics, probiotics, fecal microbiota transplantation, and combination therapies with conventional HD treatments and their applications in managing HD. The future challenges are also highlighted as the heterogeneity of gut microbiota, interindividual variability, establishing causality between gut dysbiosis and HD, identifying optimal therapeutic targets and strategies, and ensuring the long-term safety and efficacy of microbiota-based interventions. This review provides a better understanding of the potential role of gut microbiota in HD pathogenesis and guides the development of novel therapeutic approaches.}, }
@article {pmid37356723, year = {2023}, author = {Zecheng, L and Donghai, L and Runchuan, G and Yuan, Q and Qi, J and Yijia, Z and Shuaman, R and Xiaoqi, L and Yi, W and Ni, M and Yijin, Q and Liang, P and Jun, W}, title = {Fecal microbiota transplantation in obesity metabolism: A meta analysis and systematic review.}, journal = {Diabetes research and clinical practice}, volume = {202}, number = {}, pages = {110803}, doi = {10.1016/j.diabres.2023.110803}, pmid = {37356723}, issn = {1872-8227}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Metabolic Syndrome/therapy ; Obesity/therapy/metabolism ; Glucose/metabolism ; Lipids ; }, abstract = {OBJECTIVE: The effect of fecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome remains unclear. This systematic review employed a meta-analysis of RCTs for assessment on the role of FMT in treating obesity and metabolic syndrome, and its impact on clinically relevant parameters.<br><br>METHOD: Major databases and grey literatures were searched identifying RCTs comparing FMT of lean donors with placebo in obese/metabolic syndrome patients. Studies using any form of placebo were included. Variations in the parameters before and after treatment were calculated followed by meta-analyses.<br><br>RESULT: Ten studies met the inclusion criteria and a total of 334 patients were included for further analysis. Clinically significant parameters associated with obesity and metabolic syndrome were explored and FMT was identified significantly and negatively associated with most indices of abdominal adiposity including caloric intake, fasting glucose, HOMA-IR, systolic blood pressure, diastolic blood pressure, total cholesterol, HDL, LDL, triglycerides and CRP, Obesity parameters including fasting glucose and acetic acid were increased following FMT.<br><br>CONCLUSION: FMT is more advantageous for obese patients with elevated blood pressure, disordered glucose and insulin metabolism, and elevated blood lipids. The study of metabolic factors in obese patients will be our starting point in the future.}, }
@article {pmid37356668, year = {2023}, author = {Li, Z and Chen, L and Sepulveda, M and Wang, P and Rasic, M and Tullius, SG and Perkins, D and Alegre, ML}, title = {Microbiota-dependent and -independent effects of obesity on transplant rejection and hyperglycemia.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {23}, number = {10}, pages = {1526-1535}, pmid = {37356668}, issn = {1600-6143}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R25 GM109439/GM/NIGMS NIH HHS/United States ; T32 AI007090/AI/NIAID NIH HHS/United States ; R01 AG064165/AG/NIA NIH HHS/United States ; TL1 DK132769/DK/NIDDK NIH HHS/United States ; U01 AI132898/AI/NIAID NIH HHS/United States ; R01 AI115716/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Mice ; Graft Rejection/etiology ; *Glucose Intolerance/complications ; Dysbiosis/etiology ; *Gastrointestinal Microbiome ; Obesity/etiology ; Diet, High-Fat/adverse effects ; *Hyperglycemia/complications ; Inflammation/etiology ; Mice, Inbred C57BL ; }, abstract = {Obesity is associated with dysbiosis and a state of chronic inflammation that contributes to the pathogenesis of metabolic diseases, including diabetes. We have previously shown that obese mice develop glucose intolerance, increased alloreactivity, and accelerated transplant rejection. In the present study, we investigated the influence of the microbiota on diet-induced obesity (DIO)-associated transplant rejection and hyperglycemia. Antibiotic treatment prolonged graft survival and reduced fasting glycemia in high-fat diet (HFD)-fed specific-pathogen-free (SPF) mice, supporting a role for the microbiota in promoting accelerated graft rejection and hyperglycemia induced by DIO. Further supporting a microbiota-dependent effect, fecal microbiota transfer from DIO SPF mice into germ-free mice also accelerated graft rejection when compared with lean mice-fecal microbiota transfer. Notably, HFD could be also detrimental to the graft independently from microbiota, obesity, and hyperglycemia. Thus, whereas HFD-associated hyperglycemia was exclusively microbiota-dependent, HFD affected transplant outcomes via both microbiota-dependent and -independent mechanisms. Importantly, hyperglycemia in DIO SPF mice could be reduced by the addition of the gut commensal Alistipes onderdonkii, which alleviated both HFD-induced inflammation and glucose intolerance. Thus, microbial dysbiosis can be manipulated via antibiotics or select probiotics to counter some of the pathogenic effects of obesity in transplantation.}, }
@article {pmid37356123, year = {2023}, author = {Wu, X and Xuan, W and Yang, X and Liu, W and Zhang, H and Jiang, G and Cao, B and Jiang, Y}, title = {Ficolin A knockout alleviates sepsis-induced severe lung injury in mice by restoring gut Akkermansia to inhibit S100A4/STAT3 pathway.}, journal = {International immunopharmacology}, volume = {121}, number = {}, pages = {110548}, doi = {10.1016/j.intimp.2023.110548}, pmid = {37356123}, issn = {1878-1705}, mesh = {Mice ; Animals ; Akkermansia/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Interleukin-6/metabolism ; Lipopolysaccharides/metabolism ; Mice, Inbred C57BL ; Lung/metabolism ; *Acute Lung Injury/chemically induced ; *Sepsis/metabolism ; Ficolins ; }, abstract = {Acute lung injury (ALI) is a life-threatening disease with high morbidity and mortality. Our previous results demonstrated that Ficolin A (FcnA) protected against lipopolysaccharide (LPS)-induced mild ALI via activating complement, however the mechanism of severe lung damage caused by sepsis remains unclear. This study aimed to investigate whether FcnA modulated gut microbiota to affect the progression of sepsis-induced severe ALI. Fcna[-/-] and Fcnb[-/-] C57BL/6 mice were applied to establish the ALI model by injection of LPS intraperitoneally. Mice were treated with antibiotics, fecal microbiota transplantation (FMT), and intratracheal administration of recombinant protein S100A4. Changes in body weight of mice were recorded, and lung injury were assessed. Then lung tissue wet/dry weight was calculated. We found knockout of FcnA, but not FcnB, alleviated sepsis-induced severe ALI evidenced by increased body weight change, decreased wet/dry weight of lung tissue, reduced inflammatory infiltration, decreased lung damage score, decreased Muc-2, TNF-α, IL-1β, IL-6, and Cr levels, and increased sIgA levels. Furthermore, knockout of FcnA restored gut microbiota homeostasis in mice. Correlation analysis showed that Akkermansia was significantly negatively associated with TNF-α, IL-1β, and IL-6 levels in serum and bronchoalveolar lavage fluid (BALF). Moreover, knockout of FcnA regulated gut microbiota to protect ALI through S100A4. Finally, we found knockout of FcnA alleviated ALI by inhibiting S100A4 via gut Akkermansia in mice, which may provide further insights and new targets into treating sepsis-induced severe lung injury.}, }
@article {pmid37355675, year = {2023}, author = {Wang, Y and Guo, A and Zou, Y and Mu, W and Zhang, S and Shi, Z and Liu, Z and Cai, X and Zhu, XQ and Wang, S}, title = {Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulation.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {43}, pmid = {37355675}, issn = {2055-5008}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Microbiota ; *Colitis/metabolism ; *Helminths ; }, abstract = {Tissue-dwelling helminths affect billions of people around the world. They are potent manipulators of the host immune system, prominently by promoting regulatory T cells (Tregs) and are generally associated with a modified host gut microbiome. However, the role of the gut microbiota in the immunomodulatory processes for these non-intestinal parasites is still unclear. In the present study, we used an extra-intestinal cestode helminth model-larval Echinococcus multilocularis to explore the tripartite partnership (host-helminth-bacteria) in the context of regulating colonic Tregs in Balb/c mice. We showed that larval E. multilocularis infection in the peritoneal cavity attenuated colitis in Balb/c mice and induced a significant expansion of colonic Foxp3[+] Treg populations. Fecal microbiota depletion and transplantation experiments showed that the gut microbiota contributed to increasing Tregs after the helminth infection. Shotgun metagenomic and metabolic analyses revealed that the gut microbiome structure after infection was significantly shifted with a remarkable increase of Lactobacillus reuteri and that the microbial metabolic capability was reprogrammed to produce more Treg cell regulator-short-chain fatty acids in feces. Furthermore, we also prove that the L. reuteri strain elevated in infected mice was sufficient to promote the colonic Treg frequency and its growth was potentially associated with T cell-dependent immunity in larval E. multilocularis infection. Collectively, these findings indicate that the extraintestinal helminth drives expansions of host colonic Tregs through the gut microbes. This study suggests that the gut microbiome serves as a critical component of anti-inflammation effects even for a therapy based on an extraintestinal helminth.}, }
@article {pmid37354347, year = {2025}, author = {Gundluru, SB and Roy, PS and Biswal, M and Trehan, A and Kaur, J and Ray, P and Bansal, D}, title = {Isolation of Multidrug-Resistant Organisms in Surveillance Stool Culture at Diagnosis Fails to Predict Mortality or Subsequent Sepsis due to Multidrug-Resistant Organisms in Children with Acute Leukemia: A Single-Center, Prospective, Observational Study.}, journal = {Indian journal of pediatrics}, volume = {92}, number = {3}, pages = {295-298}, pmid = {37354347}, issn = {0973-7693}, mesh = {Humans ; Prospective Studies ; *Feces/microbiology ; Male ; Female ; Child, Preschool ; Child ; *Drug Resistance, Multiple, Bacterial ; *Sepsis/microbiology/mortality ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications/mortality ; Infant ; *Leukemia, Myeloid, Acute/complications/mortality ; Anti-Bacterial Agents/therapeutic use ; *Febrile Neutropenia/drug therapy/microbiology ; }, abstract = {The utility of surveillance stool culture (SSC) to guide antibiotics for febrile neutropenia (FN) is unresolved in non-transplant settings. The prospective study explored the prevalence of multidrug-resistant organisms (MDRO) in SSCs, its correlation with mortality, and the concordance of SSCs with cultures obtained during subsequent episodes of FN amongst children with acute leukemia. SSCs were obtained at presentation and 2 mo into chemotherapy. Seventy-nine patients (mean age: 5.9±3.2 y) with acute lymphoblastic leukemia (ALL) (80%), acute myeloid leukemia (AML) (16%), or biphenotypic leukemia (4%) were enrolled. MDROs were isolated from 14 (17.5%) patients in the first SSCs, including E.coli (80%), K. pneumoniae (10%), and E. faecium (10%). Three (3.8%) patients developed MDRO sepsis; none concorded with the SSCs. Eleven (14%) patients died; 4/14 (28.5%) with MDRO-colonization vis-à-vis 7/66 (10.6%) without MDRO-colonization (OR: 3.37, 95% CI: 0.8-13.6; p = 0.095). MDRO-colonization failed to predict MDRO-sepsis, bloodstream infection, or mortality. SSC failed to guide the choice of antibiotics for FN in children with acute leukemia.}, }
@article {pmid37353002, year = {2024}, author = {Gao, Y and Liang, Z and Mao, B and Zheng, X and Shan, J and Jin, C and Liu, S and Kolliputi, N and Chen, Y and Xu, F and Shi, L}, title = {Gut microbial GABAergic signaling improves stress-associated innate immunity to respiratory viral infection.}, journal = {Journal of advanced research}, volume = {60}, number = {}, pages = {41-56}, pmid = {37353002}, issn = {2090-1224}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; Mice ; *gamma-Aminobutyric Acid/metabolism ; *Immunity, Innate/immunology ; *Stress, Psychological/immunology/metabolism ; *COVID-19/immunology ; *Macrophages, Alveolar/immunology/metabolism ; Disease Models, Animal ; Signal Transduction/immunology ; Male ; SARS-CoV-2/immunology ; Influenza A virus/immunology ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation/methods ; Respiratory Tract Infections/immunology/metabolism/microbiology/virology ; }, abstract = {INTRODUCTION: Epidemiological evidences reveal that populations with psychological stress have an increased likelihood of respiratory viral infection involving influenza A virus (IAV) and SARS-CoV-2.<br><br>OBJECTIVES: This study aims to explore the potential correlation between psychological stress and increased susceptibility to respiratory viral infections and how this may contribute to a more severe disease progression.<br><br>METHODS: A chronic restraint stress (CRS) mouse model was used to infect IAV and estimate lung inflammation. Alveolar macrophages (AMs) were observed in the numbers, function and metabolic-epigenetic properties. To confirm the central importance of the gut microbiome in stress-exacerbated viral pneumonia, mice were conducted through microbiome depletion and gut microbiome transplantation.<br><br>RESULTS: Stress exposure induced a decline in Lactobacillaceae abundance and hence &#x3b3;-aminobutyric acid (GABA) level in mice. Microbial-derived GABA was released in the peripheral and sensed by AMs via GABAAR, leading to enhanced mitochondrial metabolism and &#x3b1;-ketoglutarate (&#x3b1;KG) generation. The metabolic intermediator in turn served as the cofactor for the epigenetic regulator Tet2 to catalyze DNA hydroxymethylation and promoted the PPAR&#x3b3;-centered gene program underpinning survival, self-renewing, and immunoregulation of AMs. Thus, we uncover an unappreciated GABA/Tet2/PPAR&#x3b3; regulatory circuitry initiated by the gut microbiome to instruct distant immune cells through a metabolic-epigenetic program. Accordingly, reconstitution with GABA-producing probiotics, adoptive transferring of GABA-conditioned AMs, or resumption of pulmonary &#x3b1;KG level remarkably improved AMs homeostasis and alleviated severe pneumonia in stressed mice.<br><br>CONCLUSION: Together, our study identifies microbiome-derived tonic signaling tuned by psychological stress to imprint resident immune cells and defensive response in the lungs. Further studies are warranted to translate these findings, basically from murine models, into the individuals with psychiatric stress during respiratory viral infection.}, }
@article {pmid37352702, year = {2023}, author = {Yuan, S and Wang, KS and Meng, H and Hou, XT and Xue, JC and Liu, BH and Cheng, WW and Li, J and Zhang, HM and Nan, JX and Zhang, QG}, title = {The gut microbes in inflammatory bowel disease: Future novel target option for pharmacotherapy.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {165}, number = {}, pages = {114893}, doi = {10.1016/j.biopha.2023.114893}, pmid = {37352702}, issn = {1950-6007}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/drug therapy ; *Microbiota ; *Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Gut microbes constitute the main microbiota in the human body, which can regulate biological processes such as immunity, cell proliferation, and differentiation, hence playing a specific function in intestinal diseases. In recent years, gut microbes have become a research hotspot in the pharmaceutical field. Because of their enormous number, diversity, and functional complexity, gut microbes have essential functions in the development of many digestive diseases. Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease with a complex etiology, the exact cause and pathogenesis are unclear. There are no medicines that can cure IBD, and more research on therapeutic drugs is urgently needed. It has been reported that gut microbes play a critical role in pathogenesis, and there is a tight and complex association between gut microbes and IBD. The dysregulation of gut microbes may be a predisposing factor for IBD, and at the same time, IBD may exacerbate gut microbes' disorders, but the mechanism of interaction between the two is still not well defined. The study of the relationship between gut microbes and IBD is not only important to elucidate the pathogenesis but also has a positive effect on the treatment based on the regimen of regulating gut microbes. This review describes the latest research progress on the functions of gut microbes and their relationship with IBD, which can provide reference and assistance for further research. It may provide a theoretical basis for the application of probiotics, fecal microbiota transplantation, and other therapeutic methods to regulate gut microbes in IBD.}, }
@article {pmid37351724, year = {2023}, author = {Tariq, R and Tosh, PK and Pardi, DS and Khanna, S}, title = {Reduction in urinary tract infections in patients treated with fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {42}, number = {8}, pages = {1037-1041}, pmid = {37351724}, issn = {1435-4373}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile ; Treatment Outcome ; Recurrence ; *Clostridium Infections/microbiology ; *Urinary Tract Infections/therapy/etiology ; }, abstract = {We performed an updated study to investigate the rates of urinary tract infections (UTIs) in patients with recurrent Clostridioides difficile infection (CDI) who received fecal microbiota transplantation (FMT) for CDI. We found a significant reduction in number of UTIs after FMT compared to patients who received antibiotics for CDI treatment. After FMT, we also observed a trend towards reduction of antibiotic resistance in organisms causing UTI.}, }
@article {pmid37350780, year = {2023}, author = {Han, S and Cai, L and Chen, P and Kuang, W}, title = {A study of the correlation between stroke and gut microbiota over the last 20years: a bibliometric analysis.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1191758}, pmid = {37350780}, issn = {1664-302X}, abstract = {PURPOSE: This study intends to uncover a more thorough knowledge structure, research hotspots, and future trends in the field by presenting an overview of the relationship between stroke and gut microbiota in the past two decades.<br><br>METHOD: Studies on stroke and gut microbiota correlations published between 1st January 2002 and 31st December 2021 were retrieved from the Web of Science Core Collection and then visualized and scientometrically analyzed using CiteSpace V.<br><br>RESULTS: A total of 660 papers were included in the study, among which the United States, the United Kingdom, and Germany were the leading research centers. Cleveland Clinic, Southern Medical University, and Chinese Academy of Science were the top three institutions. The NATURE was the most frequently co-cited journal. STANLEY L HAZEN was the most published author, and Tang WHW was the most cited one. The co-occurrence analysis revealed eight clusters (i.e., brain-gut microbiota axis, fecal microbiome transplantation, gut microbiota, hypertension, TMAO, ischemic stroke, neuroinflammation, atopobiosis). "gut microbiota," "Escherichia coli," "cardiovascular disease," "risk," "disease," "ischemic stroke," "stroke," "metabolism," "inflammation," and "phosphatidylcholine" were the most recent keyword explosions.<br><br>CONCLUSION: Findings suggest that in the next 10&#x2009;years, the number of publications produced annually may increase significantly. Future research trends tend to concentrate on the mechanisms of stroke and gut microbiota, with the inflammation and immunological mechanisms, TMAO, and fecal transplantation as hotspots. And the relationship between these mechanisms and a particular cardiovascular illness may also be a future research trend.}, }
@article {pmid37349964, year = {2023}, author = {Rahman, R and Fouhse, JM and Prisnee, TL and Ju, T and Diether, NE and Willing, BP}, title = {Comparing the impact of mixed-culture microbial communities and fecal transplant on the intestinal microbiota and metabolome of weaned piglets.}, journal = {FEMS microbiology ecology}, volume = {99}, number = {7}, pages = {}, doi = {10.1093/femsec/fiad068}, pmid = {37349964}, issn = {1574-6941}, mesh = {Swine ; Animals ; Female ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Weaning ; Pilot Projects ; *Microbiota ; Feces ; Metabolome ; }, abstract = {Fecal microbiota transplantation (FMT) is an emerging technique for modulating the pig microbiota, however, donor variability is one of the major reasons for inconsistent outcomes across studies. Cultured microbial communities may address some limitations of FMT; however, no study has tested cultured microbial communities as inocula in pigs. This pilot study compared the effects of microbiota transplants derived from sow feces to cultured mixed microbial community (MMC) following weaning. Control, FMT4X, and MMC4X were applied four times, while treatment FMT1X was administered once (n = 12/group). On postnatal day 48, microbial composition was modestly altered in pigs receiving FMT in comparison with Control (Adonis, P = .003), mainly attributed to reduced inter-animal variations in pigs receiving FMT4X (Betadispersion, P = .018). Pigs receiving FMT or MMC had consistently enriched ASVs assigned to genera Dialister and Alloprevotella. Microbial transplantation increased propionate production in the cecum. MMC4X piglets showed a trend of higher acetate and isoleucine compared to Control. A consistent enrichment of metabolites from amino acid metabolism in pigs that received microbial transplantation coincided with enhanced aminoacyl-tRNA biosynthesis pathway. No differences were observed among treatment groups for body weight or cytokine/chemokine profiles. Overall, FMT and MMC exerted similar effects on gut microbiota composition and metabolite production.}, }
@article {pmid37346914, year = {2023}, author = {Shrateh, ON and Jobran, A and Zaid, MA and Saleh, M}, title = {Successful management of life-threatening post-COVID-19 cryptosporidiosis in a renal transplant patient: a case report.}, journal = {The Pan African medical journal}, volume = {45}, number = {}, pages = {10}, pmid = {37346914}, issn = {1937-8688}, mesh = {Male ; Animals ; Humans ; Adult ; *Cryptosporidiosis/diagnosis ; *Cryptosporidium ; *Kidney Transplantation ; *COVID-19/complications ; Diarrhea/etiology ; Feces/parasitology ; }, abstract = {Worldwide, Cryptosporidium spp. is a common parasite that affects domestic and wild animals, including humans, and causes diarrhea in both immunocompetent and immunocompromised hosts. The fecal-oral pathway accounts for the majority of its transfer. Although C. parvum and C. hominis are the most common zoonotic species in humans, other zoonotic species can also infect immunocompetent and immunocompromised people. Patients undergoing renal transplants are more likely to contract cryptosporidiosis, which can cause severe and potentially fatal diarrhea. A 41-year-old male patient who presented to the emergency department complained of a sudden onset, severe and continuous fatigue, and a feverish sensation of two-day duration. Two days prior to the current admission, the patient started to complain of weakness affecting his whole body, as well as a fever of 39°C and continuous yellowish diarrhea occurring 4-5 times daily without blood. Stool analysis revealed a cryptosporidium infection. The patient underwent surgery for kidney transplantation. The donated kidney was the left one from his brother and was attached to the patient´s right groin. As illustrated by our example, cryptosporidiosis should be considered a significant cause of acute, persistent, watery diarrhea in immunocompromised kidney transplant recipients. Patients undergoing renal transplants should be instructed to wash their hands frequently, stay away from young animals, sick people, and swimming pools in order to lower their risk of infection.}, }
@article {pmid37346153, year = {2023}, author = {Halkjær, SI and Lo, B and Cold, F and Højer Christensen, A and Holster, S and König, J and Brummer, RJ and Aroniadis, OC and Lahtinen, P and Holvoet, T and Gluud, LL and Petersen, AM}, title = {Fecal microbiota transplantation for the treatment of irritable bowel syndrome: A systematic review and meta-analysis.}, journal = {World journal of gastroenterology}, volume = {29}, number = {20}, pages = {3185-3202}, pmid = {37346153}, issn = {2219-2840}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/etiology ; Fecal Microbiota Transplantation/adverse effects/methods ; *Gastrointestinal Microbiome ; Quality of Life ; Dysbiosis/therapy/etiology ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients' quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as 'gut dysbiosis'. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS.<br><br>AIM: To assess the efficacy and safety of FMT for the treatment of IBS.<br><br>METHODS: We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence.<br><br>RESULTS: Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision.<br><br>CONCLUSION: We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed.}, }
@article {pmid37346031, year = {2023}, author = {Ye, J and Yao, J and He, F and Sun, J and Zhao, Z and Wang, Y}, title = {Regulation of gut microbiota: a novel pretreatment for complications in patients who have undergone kidney transplantation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1169500}, pmid = {37346031}, issn = {2235-2988}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Gastrointestinal Microbiome/physiology ; Quality of Life ; *Microbiota ; Fecal Microbiota Transplantation ; }, abstract = {Kidney transplantation is an effective method to improve the condition of patients with end-stage renal disease. The gut microbiota significantly affects the immune system and can be used as an influencing factor to change the prognoses of patients who have undergone kidney transplantation. Recipients after kidney transplantation showed a lower abundance of Firmicutes and Faecalibacterium prausnitzii and a higher proportion of Bacteroidetes and Proteobacteria. After using prebiotics, synbiotics, and fecal microbiota transplantation to regulate the microbial community, the prognoses of patients who underwent kidney transplantation evidently improved. We aimed to determine the relationship between gut microbiota and various postoperative complications inpatients who have undergone kidney transplantation in recent years and to explore how gut microecology affects post-transplant complications. An in-depth understanding of the specific functions of gut microbiota and identification of the actual pathogenic flora during complications in patients undergoing kidney transplantation can help physicians develop strategies to restore the normal intestinal microbiome of transplant patients to maximize their survival and improve their quality of life.}, }
@article {pmid37344888, year = {2023}, author = {Ma, Z and Akhtar, M and Pan, H and Liu, Q and Chen, Y and Zhou, X and You, Y and Shi, D and Liu, H}, title = {Fecal microbiota transplantation improves chicken growth performance by balancing jejunal Th17/Treg cells.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {137}, pmid = {37344888}, issn = {2049-2618}, mesh = {Animals ; *T-Lymphocytes, Regulatory ; *Chickens/metabolism ; Fecal Microbiota Transplantation ; Th17 Cells ; Jejunum/metabolism ; Cytokines ; Body Weight ; }, abstract = {BACKGROUND: Intestinal inflammation has become a threatening concern in chicken production worldwide and is closely associated with Th17/Treg cell imbalance. Several studies described that gut microbiota is significantly implicated in chicken growth by modulating intestinal immune homeostasis and immune cell differentiation. Whether reshaping gut microbiota by fecal microbiota transplantation (FMT) could improve chicken growth by balancing Th17/Treg cells is an interesting question.<br><br>RESULTS: Here, the chickens with significantly different body weight from three different breeds (Turpan cockfighting&#x2009;&#xd7;&#x2009;White Leghorn chickens, white feather chickens, and yellow feather chickens) were used to compare Th17 and Treg cells. qPCR and IHC staining results indicated that Th17 cell-associated transcriptional factors Stat3 and ror&#x3b3;t and cytokines IL-6, IL-17A, and IL-21 were significantly (P&#x2009;<&#x2009;0.05) higher in the jejunum of low body weight chickens, while Treg cell-associated transcriptional factor foxp3 and cytokines TGF-&#x3b2; and IL-10 were significantly (P&#x2009;<&#x2009;0.05) lower in the jejunum of low body weight chickens, indicating imbalanced Th17/Treg cells were closely related to chicken growth performance. Transferring fecal microbiota from the healthy donor with better growth performance and abundant Lactobacillus in feces to 1-day-old chicks markedly increased growth performance (P&#x2009;<&#x2009;0.001), significantly decreased Th17 cell-associated transcriptional factors and cytokines, and increased Treg cell-associated transcriptional factors and cytokines in the jejunum (P&#x2009;<&#x2009;0.05). Furthermore, FMT increased the abundance of Lactobacillus (FMT vs Con; 84.98% vs 66.94%). Besides, the metabolites of tryptophan including serotonin, indole, and 5-methoxyindoleacetate were increased as well, which activated their receptor aryl-hydrocarbon-receptor (AhR) and expressed more CYP1A2 and IL-22 to maintain Th17/Treg cell balance and immune homeostasis.<br><br>CONCLUSION: These findings suggested that imbalanced Th17/Treg cells decreased chicken growth performance, while FMT-reshaped gut microbiota, i.e., higher Lactobacilli, increased chicken growth performance by balancing Th17/Treg cells. Video Abstract.}, }
@article {pmid37344836, year = {2023}, author = {Lin, X and Wang, M and He, Z and Hao, G}, title = {Gut microbiota mediated the therapeutic efficiency of Simiao decoction in the treatment of gout arthritis mice.}, journal = {BMC complementary medicine and therapies}, volume = {23}, number = {1}, pages = {206}, pmid = {37344836}, issn = {2662-7671}, support = {LY21H270006//Science Fund for Distinguished Young Scholars of Zhejiang Province/ ; }, mesh = {Mice ; Animals ; *Arthritis, Gouty/drug therapy ; Uric Acid ; *Gastrointestinal Microbiome ; Allopurinol/therapeutic use ; Inflammation ; }, abstract = {BACKGROUND: Gut microbiota plays a significant role in the development and treatment of gouty arthritis. Simiao decoction has been shown to alleviate gouty arthritis by inhibiting inflammation, regulating NLRP3 inflammasome, and altering gut microbiota. However, there is no evidence to prove whether gut microbiota directly mediates the therapeutic efficiency of Simiao decoction in treating gout arthritis.<br><br>METHODS: In this study, fecal microbiota transplantation (FMT) was used to transfer the gut microbiota of gout arthritis mice treated with Simiao decoction or allopurinol to blank gout arthritis mice, in order to investigate whether FMT had therapeutic effects on gout arthritis.<br><br>RESULTS: Both Simiao decoction and allopurinol effectively reduced the levels of serum uric acid, liver XOD activity, foot thickness, serum IL-1&#x3b2;, and G-CSF in gout arthritis mice. However, Simiao decoction also had additional benefits, including raising the pain threshold, reducing serum TNF-&#x3b1; and IL-6, alleviating gut inflammation, and repairing intestinal pathology, which were not observed with allopurinol treatment. Moreover, Simiao decoction had a greater impact on gut microbiota than allopurinol, as it was able to restore the abundance of phylum Proteobacteria and genus Helicobacter. After transplantation into gout arthritis mice, gut microbiota altered by Simiao decoction exhibited similar therapeutic effects to those of Simiao decoction, but gut microbiota altered by allopurinol showed no therapeutic effect.<br><br>CONCLUSIONS: These findings demonstrates that Simiao decoction can alleviate gout arthritis symptoms by regulating gut microbiota.}, }
@article {pmid37344135, year = {2023}, author = {Miguel, A}, title = {An overview of Clostridioides difficile and faecal microbiota transplant: implications for nursing practice.}, journal = {British journal of nursing (Mark Allen Publishing)}, volume = {32}, number = {12}, pages = {546-549}, doi = {10.12968/bjon.2023.32.12.546}, pmid = {37344135}, issn = {2052-2819}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Clostridioides difficile ; Feces/microbiology ; Clostridioides ; *Clostridium Infections/drug therapy/microbiology ; Anti-Bacterial Agents/therapeutic use ; Bacteria ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridioides difficile bacteria can cause excessive diarrhoea in patients, leading to further complications, such as severe dehydration and sepsis. Although C.difficile bacteria tend to reside harmlessly in many people's bowels, prolonged antibiotic use can alter the bacterial balance of the bowel resulting in a C.difficile infection. Guidance from the National Institute for Health and Care Excellence recommends treating a C.difficile infection with further antibiotic therapy; however, it also states that in cases of recurrent infection, a faecal microbiota transplant (FMT) should be considered. This article focuses on the treatment modality of FMT and is aimed at increasing awareness of the treatment. As well as discussing how the nurse can approach the topic with a patient considering FMT, the article also considers the nurse's role throughout the process.}, }
@article {pmid37343363, year = {2023}, author = {Kang, X and Ng, SK and Liu, C and Lin, Y and Zhou, Y and Kwong, TNY and Ni, Y and Lam, TYT and Wu, WKK and Wei, H and Sung, JJY and Yu, J and Wong, SH}, title = {Altered gut microbiota of obesity subjects promotes colorectal carcinogenesis in mice.}, journal = {EBioMedicine}, volume = {93}, number = {}, pages = {104670}, pmid = {37343363}, issn = {2352-3964}, mesh = {Humans ; Mice ; Animals ; *Gastrointestinal Microbiome ; *Colonic Neoplasms ; Carcinogenesis ; Obesity/complications ; Azoxymethane/toxicity ; *Colorectal Neoplasms/genetics ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {BACKGROUND: Obesity is a risk factor for colorectal cancer (CRC). The role of gut microbiota in mediating the cancer-promoting effect of obesity is unknown.<br><br>METHODS: Azoxymethane (AOM)-treated, Apc[Min/+] and germ-free mice were gavaged with feces from obese individuals and control subjects respectively. The colonic tumor load and number were recorded at the endpoint in two carcinogenic models. The gut microbiota composition and colonic transcriptome were assessed by metagenomic sequencing and RNA sequencing, respectively. The anticancer effects of bacteria depleted in fecal samples of obese individuals were validated.<br><br>FINDINGS: Conventional AOM-treated and Apc[Min/+] mice receiving feces from obese individuals showed significantly increased colon tumor formation compared with those receiving feces from control subjects. AOM-treated mice receiving feces from obese individuals showed impaired intestinal barrier function and significant upregulation of pro-inflammatory cytokines and activation of oncogenic Wnt signaling pathway. Consistently, transferring feces from obese individuals to germ-free mice led to increased colonic cell proliferation, intestinal barrier function impairment, and induction of oncogenic and proinflammatory gene expression. Moreover, germ-free mice transplanted with feces from obese human donors had increased abundance of potential pathobiont Alistipes finegoldii, and reduced abundance of commensals Bacteroides vulgatus and Akkermansia muciniphila compared with those receiving feces from human donors with normal body mass index (BMI). Validation experiments showed that B.&#xa0;vulgatus and A.&#xa0;muciniphila demonstrated anti-proliferative effects in CRC, while A.&#xa0;finegoldii promoted CRC tumor growth.<br><br>INTERPRETATION: Our results supported the role of obesity-associated microbiota in colorectal carcinogenesis and identified putative bacterial candidates that may mediate its mechanisms. Microbiota modulation in obese individuals may provide new approaches to prevent or treat obesity-related cancers including CRC.<br><br>FUNDING: This work was funded by National Key Research and Development Program of China (2020YFA0509200/2020YFA0509203), National Natural Science Foundation of China (81922082), RGC Theme-based Research Scheme Hong Kong (T21-705/20-N), RGC Research Impact Fund Hong Kong (R4632-21F), RGC-CRF Hong Kong (C4039-19GF and C7065-18GF), RGC-GRF Hong Kong (14110819, 14111621), and NTU Start-Up Grant (021337-00001).}, }
@article {pmid37343183, year = {2023}, author = {Rosenberg, J and Ritter, T}, title = {Practical use of fecal microbiota spores, live-brpk (formerly SER-109): an oral therapeutic for the prevention of recurrent Clostridioides difficile infection.}, journal = {Expert review of anti-infective therapy}, volume = {21}, number = {7}, pages = {687-690}, doi = {10.1080/14787210.2023.2219894}, pmid = {37343183}, issn = {1744-8336}, mesh = {Humans ; Spores, Bacterial ; Fecal Microbiota Transplantation ; *Microbiota ; *Clostridium Infections/prevention &amp; control ; Recurrence ; }, }
@article {pmid37339849, year = {2023}, author = {Lopetuso, LR and Deleu, S and Godny, L and Petito, V and Puca, P and Facciotti, F and Sokol, H and Ianiro, G and Masucci, L and Abreu, M and Dotan, I and Costello, SP and Hart, A and Iqbal, TH and Paramsothy, S and Sanguinetti, M and Danese, S and Tilg, H and Cominelli, F and Pizarro, TT and Armuzzi, A and Cammarota, G and Gasbarrini, A and Vermeire, S and Scaldaferri, F}, title = {The first international Rome consensus conference on gut microbiota and faecal microbiota transplantation in inflammatory bowel disease.}, journal = {Gut}, volume = {72}, number = {9}, pages = {1642-1650}, pmid = {37339849}, issn = {1468-3288}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Rome ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Colitis, Ulcerative/therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: Several randomised clinical trials (RCTs) performing faecal microbiota transplantation (FMT) for the management of inflammatory bowel disease (IBD), particularly for ulcerative colitis, have recently been published, but with major variations in study design. These include differences in administered dose, route and frequency of delivery, type of placebo and evaluated endpoints. Although the overall outcomes appear to be promising, they are highly dependent on both donor and recipient factors.<br><br>OBJECTIVE: To develop concensus-based statements and recommendations for the evaluation, management and potential treatment of IBD using FMT in order to move towards standardised practices.<br><br>DESIGN: An international panel of experts convened several times to generate evidence-based guidelines by performing a deep evaluation of currently available and/or published data. Twenty-five experts in IBD, immunology and microbiology collaborated in different working groups to provide statements on the following key issues related to FMT in IBD: (A) pathogenesis and rationale, (B) donor selection and biobanking, (C) FMT practices and (D) consideration of future studies and perspectives. Statements were evaluated and voted on by all members using an electronic Delphi process, culminating in a plenary consensus conference and generation of proposed guidelines.<br><br>RESULTS AND CONCLUSIONS: Our group has provided specific statements and recommendations, based on best available evidence, with the end goal of providing guidance and general criteria required to promote FMT as a recognised strategy for the treatment of IBD.}, }
@article {pmid37337469, year = {2023}, author = {Koop, AH and Travers, PM and Khanna, S and Pardi, DS and Farraye, FA and Hashash, JG}, title = {Fidaxomicin treatment for Clostridioides difficile infection in patients with inflammatory bowel disease.}, journal = {Journal of gastroenterology and hepatology}, volume = {38}, number = {11}, pages = {1910-1916}, doi = {10.1111/jgh.16265}, pmid = {37337469}, issn = {1440-1746}, mesh = {Adult ; Humans ; Female ; Male ; Fidaxomicin ; Anti-Bacterial Agents ; Vancomycin ; *Clostridioides difficile ; Retrospective Studies ; *Clostridium Infections/drug therapy ; *Inflammatory Bowel Diseases/complications/drug therapy ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIM: Although fidaxomicin is an effective first-line treatment for Clostridioides difficile infection, it has not been well studied in patients with inflammatory bowel disease. We aimed to assess the effectiveness of fidaxomicin for the treatment of C. difficile infection in patients with inflammatory bowel disease.<br><br>METHODS: This was a multicenter retrospective study of adults with inflammatory bowel disease and C.&#xa0;difficile infection treated with fidaxomicin with at least 3&#xa0;months of follow up. The primary outcomes were treatment response, defined as resolution of C.&#xa0;difficile infection-attributed diarrhea and/or negative C.&#xa0;difficile infection stool test, and time to C.&#xa0;difficile infection recurrence after fidaxomicin.<br><br>RESULTS: Thirty-three patients (median age 42&#xa0;years; 60.6% female) were included. Most patients had ulcerative colitis (26, 78.8%), were receiving treatment with a biologic or small molecule medication (19, 57.6%), and had a prior episode of C.&#xa0;difficile infection (26, 78.8%, median 2 episodes, range 0-15). Fidaxomicin led to resolution of C.&#xa0;difficile infection in 20 (60.6%) patients, with 6/20 (30.0%) developing a recurrence at a median of 55&#xa0;days. Most patients who failed to respond to fidaxomicin underwent fecal microbiota transplantation (10/13, 76.9%) with resolution.<br><br>CONCLUSIONS: In this cohort of patients with inflammatory bowel disease and C.&#xa0;difficile infection, 60.6% responded to treatment with fidaxomicin. Of those who did not respond, fecal microbiota transplantation was an effective therapy.}, }
@article {pmid37334140, year = {2023}, author = {Lou, X and Xue, J and Shao, R and Mo, C and Wang, F and Chen, G}, title = {Postbiotics as potential new therapeutic agents for sepsis.}, journal = {Burns &amp; trauma}, volume = {11}, number = {}, pages = {tkad022}, pmid = {37334140}, issn = {2321-3868}, abstract = {Sepsis is the main cause of death in critically ill patients and gut microbiota dysbiosis plays a crucial role in sepsis. On the one hand, sepsis leads to the destruction of gut microbiota and induces and aggravates terminal organ dysfunction. On the other hand, the activation of pathogenic gut flora and the reduction in beneficial microbial products increase the susceptibility of the host to sepsis. Although probiotics or fecal microbiota transplantation preserve gut barrier function on multiple levels, their efficacy in sepsis with intestinal microbiota disruptions remains uncertain. Postbiotics consist of inactivated microbial cells or cell components. They possess antimicrobial, immunomodulatory, antioxidant and antiproliferative activities. Microbiota-targeted therapy strategies, such as postbiotics, may reduce the incidence of sepsis and improve the prognosis of patients with sepsis by regulating gut microbial metabolites, improving intestinal barrier integrity and changing the composition of the gut microbiota. They offer a variety of mechanisms and might even be superior to more conventional 'biotics' such as probiotics and prebiotics. In this review, we present an overview of the concept of postbiotics and summarize what is currently known about postbiotics and their prospective utility in sepsis therapy. Overall, postbiotics show promise as a viable adjunctive therapy option for sepsis.}, }
@article {pmid37333464, year = {2023}, author = {Lee, C and Louie, T and Bancke, L and Guthmueller, B and Harvey, A and Feuerstadt, P and Khanna, S and Orenstein, R and Dubberke, ER}, title = {Safety of fecal microbiota, live-jslm (REBYOTA[™]) in individuals with recurrent Clostridioides difficile infection: data from five prospective clinical trials.}, journal = {Therapeutic advances in gastroenterology}, volume = {16}, number = {}, pages = {17562848231174277}, pmid = {37333464}, issn = {1756-283X}, abstract = {BACKGROUND: Microbiota-based treatments reduce the incidence of recurrent Clostridioides difficile infections (rCDIs), but prospectively collected safety data needed to broaden patient access and protect public health have been limited.<br><br>OBJECTIVES: We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) - the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration - for preventing rCDI in adults.<br><br>DESIGN: Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL.<br><br>METHODS: Trial participants were at least 18&#x2009;years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or two doses of RBL (or placebo) administered rectally, depending on the trial design. In four of the five trials, participants with CDI recurrence within 8&#x2009;weeks after RBL or placebo administration were eligible for treatment with open-label RBL. Treatment-emergent adverse events (TEAEs) were recorded for at least 6&#x2009;months following last study treatment; in PUNCH CD2 and PUNCH Open-Label trials, TEAEs and serious TEAEs were collected through 12 and 24&#x2009;months, respectively.<br><br>RESULTS: Among the five trials, 978 participants received at least one dose of RBL (assigned treatment or after recurrence) and 83 participants received placebo only. TEAEs were reported in 60.2% of Placebo Only participants and 66.4% of RBL Only participants. Only abdominal pain, nausea, and flatulence were significantly higher in the RBL Only group compared with the Placebo Only group. Most TEAEs were mild or moderate in severity and were most frequently related to preexisting conditions. There were no reported infections for which the causative pathogen was traced to RBL. Potentially life-threatening TEAEs were infrequent (3.0% of participants).<br><br>CONCLUSION: Across five clinical trials, RBL was well tolerated in adults with rCDI. In aggregate, these data consistently demonstrated the safety of RBL.}, }
@article {pmid37323141, year = {2023}, author = {Khatoon, S and Kalam, N and Rashid, S and Bano, G}, title = {Effects of gut microbiota on neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1145241}, pmid = {37323141}, issn = {1663-4365}, abstract = {A progressive degradation of the brain's structure and function, which results in a reduction in cognitive and motor skills, characterizes neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The morbidity linked to NDs is growing, which poses a severe threat to human being's mental and physical ability to live well. The gut-brain axis (GBA) is now known to have a crucial role in the emergence of NDs. The gut microbiota is a conduit for the GBA, a two-way communication system between the gut and the brain. The myriad microorganisms that make up the gut microbiota can affect brain physiology by transmitting numerous microbial chemicals from the gut to the brain via the GBA or neurological system. The synthesis of neurotransmitters, the immunological response, and the metabolism of lipids and glucose have all been demonstrated to be impacted by alterations in the gut microbiota, such as an imbalance of helpful and harmful bacteria. In order to develop innovative interventions and clinical therapies for NDs, it is crucial to comprehend the participation of the gut microbiota in these conditions. In addition to using antibiotics and other drugs to target particular bacterial species that may be a factor in NDs, this also includes using probiotics and other fecal microbiota transplantation to maintain a healthy gut microbiota. In conclusion, the examination of the GBA can aid in understanding the etiology and development of NDs, which may benefit the improvement of clinical treatments for these disorders and ND interventions. This review indicates existing knowledge about the involvement of microbiota present in the gut in NDs and potential treatment options.}, }
@article {pmid37321188, year = {2023}, author = {Mairinger, M and Maget, A and Wagner-Skacel, J and Mörkl, S and Dalkner, N and Hellinger, T and Birner, A and Fellendorf, FT and Platzer, M and Kreuzer, K and Queissner, R and Reininghaus, B and Lenger, M and Fabisch, K and Fitz, W and Kohlhammer-Dohr, A and Krammer, A and Holl, AK and Painold, A and Häussl, A and Stross, TM and Schmiedhofer, F and Tmava-Berisha, A and Pahsini, K and Marinschek, S and Wenninger, J and Hamm, C and Pilz, R and Lehofer, M and Amouzadeh-Ghadikolai, O and Horvath, A and Kainz, G and Gallé, B and Dinan, TG and Butler, MI and Reininghaus, E and Bengesser, S}, title = {Gut Microbiome Composition and Its Association with Sleep in Major Psychiatric Disorders.}, journal = {Neuropsychobiology}, volume = {82}, number = {4}, pages = {220-233}, doi = {10.1159/000530386}, pmid = {37321188}, issn = {1423-0224}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Depressive Disorder, Major ; RNA, Ribosomal, 16S/genetics ; Cross-Sectional Studies ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; *Mental Disorders/diagnosis ; Sleep ; *Sleep Wake Disorders ; }, abstract = {INTRODUCTION: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality.<br><br>METHODS: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera.<br><br>RESULTS: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI >8), compared to poor-sleep quality patients (PSQI &#x2264;8).<br><br>CONCLUSION: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances.}, }
@article {pmid37318134, year = {2023}, author = {Gonzales-Luna, AJ and Carlson, TJ and Garey, KW}, title = {Gut microbiota changes associated with Clostridioides difficile infection and its various treatment strategies.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2223345}, pmid = {37318134}, issn = {1949-0984}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis/therapy ; *Microbiota ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/therapy ; }, abstract = {Human gut microbiota are critical to both the development of and recovery from Clostridioides difficile infection (CDI). Antibiotics are the mainstay of CDI treatment, yet inherently cause further imbalances in the gut microbiota, termed dysbiosis, complicating recovery. A variety of microbiota-based therapeutic approaches are in use or in development to limit disease- and treatment-associated dysbiosis and improve rates of sustained cure. These include the recently FDA-approved fecal microbiota, live-jslm (formerly RBX2660) and fecal microbiota spores, live-brpk (formerly SER-109), which represent a new class of live biotherapeutic products (LBPs), traditional fecal microbiota transplantation (FMT), and ultra-narrow-spectrum antibiotics. Here, we aim to review the microbiome changes associated with CDI as well as a variety of microbiota-based treatment approaches.}, }
@article {pmid37317246, year = {2023}, author = {Hsu, M and Tun, KM and Batra, K and Haque, L and Vongsavath, T and Hong, AS}, title = {Safety and Efficacy of Fecal Microbiota Transplantation in Treatment of Inflammatory Bowel Disease in the Pediatric Population: A Systematic Review and Meta-Analysis.}, journal = {Microorganisms}, volume = {11}, number = {5}, pages = {}, pmid = {37317246}, issn = {2076-2607}, abstract = {Background and Aims: Fecal microbiota transplantation (FMT) has been increasingly studied in the inflammatory bowel disease (IBD) population. However, most studies have focused on the adult population, and the safety and efficacy of FMT in a pediatric population is less well understood. This systematic review and meta-analysis investigates the safety and efficacy of FMT in a pediatric IBD population. Methods: A comprehensive literature search of publications published prior to 30 June 2022 was undertaken. Safety data, IBD-related outcomes, and microbiome analysis were obtained from these studies when accessible. Individual estimates of each study were pooled, and sensitivity analysis was conducted. Results: Eleven studies satisfied our eligibility criteria. The calculated pooled rate of adverse events was 29% (95% confidence interval [CI]: 15.0%, 44.0%; p < 0.001; I2 = 89.0%, Q = 94.53), and the calculated pooled rate of serious adverse events was 10% (95% confidence interval [CI]: 6.0%, 14.0%; p = 0.28; I2 = 18.0%, Q = 9.79). One month after FMT, clinical response was achieved in 20/34 (58.8%) pediatric IBD patients, clinical remission was achieved in 22/34 (64.7%), and both clinical response and remission were achieved in 15/34 (44.1%) pediatric IBD patients. Conclusions: FMT can be a safe and effective treatment in the pediatric IBD population and may demonstrate improved safety and efficacy in the pediatric population compared to the adult population. However, our results are limited by a lack of established protocol as well as long-term follow-up for FMT in a pediatric IBD population.}, }
@article {pmid37317027, year = {2023}, author = {Stols-Gonçalves, D and Mak, AL and Madsen, MS and van der Vossen, EWJ and Bruinstroop, E and Henneman, P and Mol, F and Scheithauer, TPM and Smits, L and Witjes, J and Meijnikman, AS and Verheij, J and Nieuwdorp, M and Holleboom, AG and Levin, E}, title = {Faecal Microbiota transplantation affects liver DNA methylation in Non-alcoholic fatty liver disease: a multi-omics approach.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2223330}, pmid = {37317027}, issn = {1949-0984}, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/therapy ; Fecal Microbiota Transplantation ; DNA Methylation ; Multiomics ; *Gastrointestinal Microbiome ; Choline ; }, abstract = {Individuals with nonalcoholic fatty liver disease (NAFLD) have an altered gut microbiota composition. Moreover, hepatic DNA methylation may be altered in the state of NAFLD. Using a fecal microbiota transplantation (FMT) intervention, we aimed to investigate whether a change in gut microbiota composition relates to altered liver DNA methylation in NAFLD. Moreover, we assessed whether plasma metabolite profiles altered by FMT relate to changes in liver DNA methylation. Twenty-one individuals with NAFLD underwent three 8-weekly vegan allogenic donor (n = 10) or autologous (n = 11) FMTs. We obtained hepatic DNA methylation profiles from paired liver biopsies of study participants before and after FMTs. We applied a multi-omics machine learning approach to identify changes in the gut microbiome, peripheral blood metabolome and liver DNA methylome, and analyzed cross-omics correlations. Vegan allogenic donor FMT compared to autologous FMT induced distinct differential changes in I) gut microbiota profiles, including increased abundance of Eubacterium siraeum and potential probiotic Blautia wexlerae; II) plasma metabolites, including altered levels of phenylacetylcarnitine (PAC) and phenylacetylglutamine (PAG) both from gut-derived phenylacetic acid, and of several choline-derived long-chain acylcholines; and III) hepatic DNA methylation profiles, most importantly in Threonyl-TRNA Synthetase 1 (TARS) and Zinc finger protein 57 (ZFP57). Multi-omics analysis showed that Gemmiger formicillis and Firmicutes bacterium_CAG_170 positively correlated with both PAC and PAG. E siraeum negatively correlated with DNA methylation of cg16885113 in ZFP57. Alterations in gut microbiota composition by FMT caused widespread changes in plasma metabolites (e.g. PAC, PAG, and choline-derived metabolites) and liver DNA methylation profiles in individuals with NAFLD. These results indicate that FMTs might induce metaorganismal pathway changes, from the gut bacteria to the liver.}, }
@article {pmid37315113, year = {2023}, author = {Halsey, TM and Thomas, AS and Hayase, T and Ma, W and Abu-Sbeih, H and Sun, B and Parra, ER and Jiang, ZD and DuPont, HL and Sanchez, C and El-Himri, R and Brown, A and Flores, I and McDaniel, L and Ortega Turrubiates, M and Hensel, M and Pham, D and Watowich, SS and Hayase, E and Chang, CC and Jenq, RR and Wang, Y}, title = {Microbiome alteration via fecal microbiota transplantation is effective for refractory immune checkpoint inhibitor-induced colitis.}, journal = {Science translational medicine}, volume = {15}, number = {700}, pages = {eabq4006}, pmid = {37315113}, issn = {1946-6242}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; }, mesh = {*Immune Checkpoint Inhibitors/adverse effects ; *Colitis/chemically induced/therapy ; *Fecal Microbiota Transplantation/methods ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Humans ; Male ; Female ; Middle Aged ; Aged ; }, abstract = {Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line immunosuppression (infliximab or vedolizumab). Ten patients (83%) achieved symptom improvement after FMT, and three patients (25%) required repeat FMT, two of whom had no subsequent response. At the end of the study, 92% achieved IMC clinical remission. 16S rRNA sequencing of patient stool samples revealed that compositional differences between FMT donors and patients with IMC before FMT were associated with a complete response after FMT. Comparison of pre- and post-FMT stool samples in patients with complete responses showed significant increases in alpha diversity and increases in the abundances of Collinsella and Bifidobacterium, which were depleted in FMT responders before FMT. Histologically evaluable complete response patients also had decreases in select immune cells , including CD8[+] T cells, in the colon after FMT when compared with non-complete response patients (n = 4). This study validates FMT as an effective treatment strategy for IMC and gives insights into the microbial signatures that may play a critical role in FMT response.}, }
@article {pmid37313343, year = {2023}, author = {Wang, Y and Sun, J and Xie, S and Zhou, Y and Wang, T and Liu, Z and Li, C and Gao, L and Pan, T}, title = {Increased abundance of bacteria of the family Muribaculaceae achieved by fecal microbiome transplantation correlates with the inhibition of kidney calcium oxalate stone deposition in experimental rats.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1145196}, pmid = {37313343}, issn = {2235-2988}, mesh = {Male ; Rats ; Animals ; Guinea Pigs ; *Calcium Oxalate ; Fecal Microbiota Transplantation ; Renin ; Creatinine ; RNA, Ribosomal, 16S/genetics ; Uric Acid ; Rats, Sprague-Dawley ; Kidney/physiology ; Bacteria/genetics ; Bacteroidetes ; *Kidney Calculi/therapy ; Oxalic Acid ; }, abstract = {BACKGROUND: The incidence of nephrolithiasis is increasing rapidly worldwide. Calcium oxalate is the most common constituent, contributing to approximately 80% of all kidney stones. The gut microbiome, through its oxalate-degrading ability, may play a role in decreasing morbidity due to urinary calculus. Fecal microbiome transplantation (FMT) has been reported to be effective in restoring the gastrointestinal microbial community in different conditions. The transplantation of whole communities that have oxalate-degrading function may be a more effective strategy than the transplantation of isolated strains.<br><br>METHODS: FMT was carried out in male guinea pigs and male Sprague-Dawley laboratory rats (SDRs). Fresh feces were collected from guinea pigs housed in metabolic cages. SDRs were divided into four groups: two groups received standard rat chow (SC) (groups SC and SC + FMT), and two groups were fed a 5% potassium oxalate diet (OD) (groups OD + phosphate-buffered saline (PBS) and OD + FMT). On day 14, groups OD + PBS, OD + FMT, and SC + FMT received either PBS or guinea pig feces by esophageal gavage. The composition of the microbiota of guinea pigs and SDRs was analyzed using a 16S rRNA gene sequencing approach. Biochemical analysis of urine samples from SDRs revealed the presence of calcium oxalate (CaOx) crystals, which were presumed to originate from kidney stones. Renal function was examined using real-time PCR analysis and immunohistochemical staining for renin, angiotensin-converting enzyme, and osteopontin (OPN) expression.<br><br>RESULTS: FMT resulted in a gut microbiota that was a mixture of guinea pig and SDR bacteria. A microbial network involving Muribaculaceae, Lactobacillus, and Bifidobacterium was activated by FMT in group OD + FMT. As a result, urinary oxalate, calcium, uric acid, creatinine and urea in urine samples were reduced significantly. Similarly, significant reduction of uric acid and blood urea nitrogen to creatinine ratio in serum samples was observed (p < 0.05). Microscopic observations revealed a high CaOx crystal score (4+) in the kidneys of rats in group OD + PBS, whereas a lower score (2+) was observed in the rats in group OD + FMT. Up-regulation of OPN and down-regulation of renin were also associated with FMT.<br><br>CONCLUSION: A microbial network involving Muribaculaceae and other oxalate-degrading bacteria achieved by FMT was capable of reducing urinary oxalate excretion and CaOx crystal deposition in the kidney through increasing intestinal oxalate degradation. FMT may exert a renoprotective function in oxalate-related kidney stones.}, }
@article {pmid37309179, year = {2023}, author = {Xia, J and Guo, W and Hu, M and Jin, X and Zhang, S and Liu, B and Qiu, H and Wang, K and Zhuge, A and Li, S and Ji, Z and Li, L and Xu, K}, title = {Resynchronized rhythmic oscillations of gut microbiota drive time-restricted feeding induced nonalcoholic steatohepatitis alleviation.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2221450}, pmid = {37309179}, issn = {1949-0984}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Non-alcoholic Fatty Liver Disease ; *Microbiota ; Fasting ; Intermittent Fasting ; Clostridiales ; }, abstract = {With the drive of the endogenous circadian clock and external cues such as feeding behavior, the microbial community generates rhythmic oscillations in composition and function. Microbial oscillations are crucial in orchestrating host metabolic homeostasis during the predictable 24-hour diurnal cycle. A time-restricted feeding (TRF) regimen is a promising dietary strategy to optimize energy utilization, alleviate metabolic syndrome and reinforce microbial cyclical fluctuations. However, the causative relationship between reinforced microbial rhythmicity and TRF-induced metabolic improvement remains elusive. In this study, we corroborated that the TRF regimen notably alleviated obesity and nonalcoholic steatohepatitis (NASH) with reinstated rhythmicity of genera such as Lactobacillus, Mucispirillum, Acetatifactor, and Lachnoclostridium. The reshaped microbial oscillations correlate with cyclical fluctuations in intestinal amino acids. Furthermore, fecal microbiota transplantation (FMT) indicated that only the TRF feeding phase-derived microbiota, but not the TRF fasting phase-derived microbiota, could protect mice from NASH and reinstate microbial rhythmicity, confirming that the microbiota improved NASH in a time-of-day-specific manner. The unique role of the TRF-feeding phase-derived microbiota was accompanied by regulation of the serotonergic synapse pathway and rejuvenation of the microbial production of indole derivatives. Our results revealed the discrepant characteristics between the feeding and fasting phases and the time-of-day-specific configuration of microbiota functionality in the TRF regimen.}, }
@article {pmid37308187, year = {2023}, author = {Zhong, P and Xu, Y and Ye, S and Yang, F and Wu, L and Su, G and Liu, Y and Feng, J and Wang, Y and Wu, Z and Zheng, Z}, title = {[A preliminary study on the effects of fecal microbiota transplantation on the intestinal microecology of patients with severe pneumonia during the convalescence period].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {35}, number = {4}, pages = {352-357}, doi = {10.3760/cma.j.cn121430-20221206-01065}, pmid = {37308187}, issn = {2095-4352}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Complement C3 ; Convalescence ; Prospective Studies ; Feces ; }, abstract = {OBJECTIVE: To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period.<br><br>METHODS: A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group.<br><br>RESULTS: The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68&#xb1;0.27 vs. 0.80&#xb1;0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the &#x3b1; diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and &#x3b2; diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030).<br><br>CONCLUSIONS: FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.}, }
@article {pmid37307732, year = {2023}, author = {Zhao, Q and Hao, Y and Yang, X and Mao, J and Tian, F and Gao, Y and Tian, X and Yan, X and Qiu, Y}, title = {Mitigation of maternal fecal microbiota transplantation on neurobehavioral deficits of offspring rats prenatally exposed to arsenic: Role of microbiota-gut-brain axis.}, journal = {Journal of hazardous materials}, volume = {457}, number = {}, pages = {131816}, doi = {10.1016/j.jhazmat.2023.131816}, pmid = {37307732}, issn = {1873-3336}, mesh = {Rats ; Animals ; Pregnancy ; Female ; *Fecal Microbiota Transplantation ; Toll-Like Receptor 4/genetics/metabolism ; Brain-Gut Axis ; *Arsenic/toxicity/metabolism ; NF-kappa B/metabolism ; Lipopolysaccharides/toxicity ; Myeloid Differentiation Factor 88/metabolism ; }, abstract = {It is established that gut microbiota dysbiosis is implicated in arsenic (As)-induced neurotoxic process, however, the underlying mode of action remains largely unclear. Here, through remodeling gut microbiota on As-intoxicated pregnancy rats using fecal microbiota transplantation (FMT) from Control rats, neuronal loss and neurobehavioral deficits in offspring prenatally exposed to As were significantly alleviated after maternal FMT treatment. In prenatal As-challenged offspring after maternal FMT treatment, remarkably, suppressed expression of inflammatory cytokines in tissues (colon, serum, and striatum) were observed along with reversed mRNA and protein expression of tight junction related molecules in intestinal barrier and blood-brain barrier (BBB); Further, expression of serum lipopolysaccharide (LPS), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and nuclear transcription factor-κB (NF-κB) in colonic and striatal tissues were repressed with activation of astrocytes and microglia inhibited. In particular, tightly correlated and enriched microbiomes were identified such as higher-expressed g_Prevotella, g_UCG_005, and lower-expressed p_Desulfobacterota, g_Eubacterium_xylanophilum_group. Collectively, our results first demonstrated that reconstruction of normal gut microbiota by maternal FMT treatment alleviated prenatal As-induced overall inflammatory state and impairments of intestinal barrier and BBB integrity by impeding LPS-mediated TLR4/Myd88/NF-κB signaling pathway through microbiota-gut-brain axis, which provides a novel therapeutic avenue for developmental arsenic neurotoxicity.}, }
@article {pmid37307215, year = {2023}, author = {Kashyap, S and Das, A}, title = {Exploring the complex and multifaceted interplay of the gut microbiome and cancer prevention and therapy.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {70}, number = {2}, pages = {85-99}, doi = {10.1556/030.2023.02054}, pmid = {37307215}, issn = {1588-2640}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota/physiology ; *Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Immunotherapy ; *Neoplasms/prevention &amp; control ; }, abstract = {Recent scientific research has indicated that the gut microbiota constitutes a nuanced, diverse ecosystem of microorganisms that have gained significant attention due to its crucial involvement in shaping human health and diseases. In particular, the gut microbiota plays a pivotal role in cancer prevention, and disturbances in its composition and function, known as dysbiosis, that have been linked to an increased risk of developing various malignancies. The gut microbiota exerts a myriad of effects on the production of anti-cancer compounds, the host's immune system and inflammation, underscoring its crucial involvement in cancer. Additionally, recent studies have shown that the gut microbiota has a role in the development of cancer, influencing cancer risk, co-infections, disease progression, and treatment response. The observation of reduced efficacy of immunotherapy in patients receiving antibiotic treatment indicates a substantial influence of the microbiota in mediating the toxicity and response of cancer therapy, notably immunotherapy, and its immune-related side effects. A growing body of research has focused on cancer treatments that target the microbiome, including probiotics, dietary modifications, and faecal microbiota transplantation (FMT). The forthcoming era of personalised cancer therapies is anticipated to prioritise tumor evolution, molecular and phenotypic heterogeneity, and immunological profiling, with gut microbiota assuming a pivotal position in this domain. This review aims to offer clinicians a comprehensive perspective on the microbiota-cancer axis, including its influence on cancer prevention and therapy and highlights the importance of integrating microbiome science into the design and implementation of cancer therapies.}, }
@article {pmid37306423, year = {2023}, author = {Ishimwe, JA and Zhong, J and Kon, V and Kirabo, A}, title = {Murine Fecal Isolation and Microbiota Transplantation.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {195}, pages = {}, doi = {10.3791/64310}, pmid = {37306423}, issn = {1940-087X}, support = {UL1 TR002243/TR/NCATS NIH HHS/United States ; R03 HL155041/HL/NHLBI NIH HHS/United States ; R01 HL144941/HL/NHLBI NIH HHS/United States ; P01 HL116263/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; *Cardiovascular Diseases ; Dysbiosis ; *Microbiota ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, abstract = {Gut microbiota dysbiosis plays a role in the pathophysiology of cardiovascular and metabolic disorders, but the mechanisms are not well understood. Fecal microbiota transplantation (FMT) is a valuable approach to delineating a direct role of the total microbiota or isolated species in disease pathophysiology. It is a safe treatment option for patients with recurrent Clostridium difficile infection. Preclinical studies demonstrate that manipulating the gut microbiota is a useful tool to study the mechanistic link between dysbiosis and disease. Fecal microbiota transplantation may help elucidate novel gut microbiota-targeted therapeutics for the management and treatment of cardiometabolic disease. Despite a high success rate in rodents, there remains translational changes associated with the transplantation. The goal here is to provide guidance in studying the effects of gut microbiome in experimental cardiovascular disease. In this study, a detailed protocol for the collection, handling, processing, and transplantation of fecal microbiota in murine studies is described. The collection and processing steps are described for both human and rodent donors. Lastly, we describe using a combination of the Swiss-rolling and immunostaining techniques to assess gut-specific morphology and integrity changes in cardiovascular disease and related gut microbiota mechanisms.}, }
@article {pmid37301689, year = {2023}, author = {Dini-Andreote, F and Custer, GF}, title = {Ecological principles of fecal microbiota transplantation.}, journal = {Trends in microbiology}, volume = {31}, number = {8}, pages = {776-779}, doi = {10.1016/j.tim.2023.05.009}, pmid = {37301689}, issn = {1878-4380}, mesh = {Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Microbiota ; Feces ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a procedure used to treat diseases related to microbiome imbalances. We discuss how ecological principles can inform the design of FMT clinical trials and contribute to data interpretation. This effort will promote a better understanding of microbiome engraftment and assist the development of clinical protocols.}, }
@article {pmid37301133, year = {2023}, author = {Cai, Y and Kang, Y}, title = {Gut microbiota and metabolites in diabetic retinopathy: Insights into pathogenesis for novel therapeutic strategies.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {164}, number = {}, pages = {114994}, doi = {10.1016/j.biopha.2023.114994}, pmid = {37301133}, issn = {1950-6007}, mesh = {Animals ; *Diabetic Retinopathy/drug therapy ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology ; Inflammation/pathology ; Retina ; *Diabetes Mellitus/pathology ; }, abstract = {Diabetic retinopathy (DR) is the most common and detrimental microvascular complication of diabetes mellitus. It has become one of the top causes of blindness and visual impairment in the working-age population. However, prevention and treatment options for DR are limited, invasive, and expensive, and most are focused on advanced-stage disease. The gut microbiota is an intricate system that alters the body's microenvironment, and its dysbiosis is strongly associated with DR. Recently, more and more investigations into the relationship between microbiota and DR have enhanced our understanding of how the gut microbiota influences the occurrence, development, prevention, and treatment of DR. In this review, we summarize the changes in the gut microbiota of animals and patients with DR and the function of metabolites and anti-diabetes drugs. Furthermore, we discuss the potential use of gut microbiota as an early diagnostic marker and targeting for DR in the healthy people and diabetic patients. Finally, the microbiota-gut-retina axis is presented to help us understand the mechanisms underlying the effect of gut microbiota on triggering or promoting DR, with a focus on the key pathways (e.g., bacterial dysbiosis and gut barrier dysfunction) that promote inflammation, insulin resistance, retinal cell and acellular capillary damage, leading to DR. Based on these data, we can hope to achieve a non-invasive, inexpensive treatment for DR by modulating the gut microbiota, either by supplementation with probiotics or by fecal transplantation. We outline the gut microbiota-targeting treatments in detail that could prevent DR progression.}, }
@article {pmid37299462, year = {2023}, author = {Lupu, VV and Trandafir, LM and Raileanu, AA and Mihai, CM and Morariu, ID and Starcea, IM and Mocanu, A and Butnariu, LI and Stoleriu, G and Salaru, DL and Chisnoiu, T and Munteanu, D and Mitrofan, C and Lupu, A}, title = {Advances in Understanding the Human Gut Microbiota and Its Implication in Pediatric Celiac Disease-A Narrative Review.}, journal = {Nutrients}, volume = {15}, number = {11}, pages = {}, pmid = {37299462}, issn = {2072-6643}, mesh = {Humans ; Child ; *Celiac Disease ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology ; Glutens/adverse effects ; Diet, Gluten-Free ; }, abstract = {Celiac disease (CD) is a multifactorial disorder, defined by a complex interplay of genetic and environmental factors. Both genetic predisposition and dietary exposure to gluten are essential factors in triggering CD. However, there is proof that their presence is necessary, but not sufficient, for disease development. Through gut microbiota modulation, several additional environmental factors have shown their potential role as co-factors in CD pathogenesis. The aim of this review is to illustrate the possible mechanisms that stand behind the gut microbiota's involvement in CD pathogenesis. Furthermore, we discuss microbiota manipulation's potential role as both a preventative and therapeutic option. The available literature provides evidence that even before CD onset, factors including cesarean birth and formula feeding, as well as intestinal infection exposure, amplify the risk of CD in genetically predisposed individuals, due to their influence on the intestinal microbiome composition. Active CD was associated with elevated levels of several Gram-negative bacterial genera, including Bacteroides, Escherichia, and Prevotella, while beneficial bacteria such as lactobacilli and bifidobacteria were less abundant. Viral and fungal dysbiosis has also been described in CD, evidencing specific taxa alteration. A gluten-free diet (GFD) may improve the clinical symptoms and duodenal histopathology, but the persistence of intestinal dysbiosis in CD children under a GFD urges the need for additional therapy. Probiotics, prebiotics, and fecal microbial transplant have demonstrated their efficacy in restoring gut microbiota eubiosis in adult CD patients; however, their efficacy and safety as adjunctive therapies to a GFD in pediatric patients needs further investigation.}, }
@article {pmid37299414, year = {2023}, author = {Hughes, RL and Frankenfeld, CL and Gohl, DM and Huttenhower, C and Jackson, SA and Vandeputte, D and Vogtmann, E and Comstock, SS and Kable, ME}, title = {Methods in Nutrition &amp; Gut Microbiome Research: An American Society for Nutrition Satellite Session [13 October 2022].}, journal = {Nutrients}, volume = {15}, number = {11}, pages = {}, pmid = {37299414}, issn = {2072-6643}, support = {IAFNS-HUGESRILEY-20221026//Institute for the Advancement of Food and Nutrition Sciences/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Nutritional Status ; *Microbiota ; Research ; *Nutrition Therapy ; }, abstract = {The microbial cells colonizing the human body form an ecosystem that is integral to the regulation and maintenance of human health. Elucidation of specific associations between the human microbiome and health outcomes is facilitating the development of microbiome-targeted recommendations and treatments (e.g., fecal microbiota transplant; pre-, pro-, and post-biotics) to help prevent and treat disease. However, the potential of such recommendations and treatments to improve human health has yet to be fully realized. Technological advances have led to the development and proliferation of a wide range of tools and methods to collect, store, sequence, and analyze microbiome samples. However, differences in methodology at each step in these analytic processes can lead to variability in results due to the unique biases and limitations of each component. This technical variability hampers the detection and validation of associations with small to medium effect sizes. Therefore, the American Society for Nutrition (ASN) Nutritional Microbiology Group Engaging Members (GEM), sponsored by the Institute for the Advancement of Food and Nutrition Sciences (IAFNS), hosted a satellite session on methods in nutrition and gut microbiome research to review currently available methods for microbiome research, best practices, as well as tools and standards to aid in comparability of methods and results. This manuscript summarizes the topics and research discussed at the session. Consideration of the guidelines and principles reviewed in this session will increase the accuracy, precision, and comparability of microbiome research and ultimately the understanding of the associations between the human microbiome and health.}, }
@article {pmid37298527, year = {2023}, author = {Bicknell, B and Liebert, A and Borody, T and Herkes, G and McLachlan, C and Kiat, H}, title = {Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298527}, issn = {1422-0067}, mesh = {Animals ; Humans ; Brain-Gut Axis ; *Neurodegenerative Diseases/metabolism ; *Autism Spectrum Disorder/metabolism ; Dysbiosis/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism ; *Microbiota ; Brain/metabolism ; }, abstract = {The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases. This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.}, }
@article {pmid37295406, year = {2023}, author = {Nguyen, CL and Markey, KA and Miltiadous, O and Dai, A and Waters, N and Sadeghi, K and Fei, T and Shouval, R and Taylor, BP and Liao, C and Slingerland, JB and Slingerland, AE and Clurman, AG and Maloy, MA and Bohannon, L and Giardina, PA and Brereton, DG and Armijo, GK and Fontana, E and Gradissimo, A and Gyurkocza, B and Sung, AD and Chao, NJ and Devlin, SM and Taur, Y and Giralt, SA and Perales, MA and Xavier, JB and Pamer, EG and Peled, JU and Gomes, ALC and van den Brink, MRM}, title = {High-resolution analyses of associations between medications, microbiome, and mortality in cancer patients.}, journal = {Cell}, volume = {186}, number = {12}, pages = {2705-2718.e17}, pmid = {37295406}, issn = {1097-4172}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; R56 AI137269/AI/NIAID NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; R21 AG066388/AG/NIA NIH HHS/United States ; R01 HL151365/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 CA203950/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; Metagenome ; *Hematopoietic Stem Cell Transplantation ; Anti-Bacterial Agents ; *Neoplasms/drug therapy ; }, abstract = {Discerning the effect of pharmacological exposures on intestinal bacterial communities in cancer patients is challenging. Here, we deconvoluted the relationship between drug exposures and changes in microbial composition by developing and applying a new computational method, PARADIGM (parameters associated with dynamics of gut microbiota), to a large set of longitudinal fecal microbiome profiles with detailed medication-administration records from patients undergoing allogeneic hematopoietic cell transplantation. We observed that several non-antibiotic drugs, including laxatives, antiemetics, and opioids, are associated with increased Enterococcus relative abundance and decreased alpha diversity. Shotgun metagenomic sequencing further demonstrated subspecies competition, leading to increased dominant-strain genetic convergence during allo-HCT that is significantly associated with antibiotic exposures. We integrated drug-microbiome associations to predict clinical outcomes in two validation cohorts on the basis of drug exposures alone, suggesting that this approach can generate biologically and clinically relevant insights into how pharmacological exposures can perturb or preserve microbiota composition. The application of a computational method called PARADIGM to a large dataset of cancer patients' longitudinal fecal specimens and detailed daily medication records reveals associations between drug exposures and the intestinal microbiota that recapitulate in vitro findings and are also predictive of clinical outcomes.}, }
@article {pmid37294712, year = {2023}, author = {Sheykhsaran, E and Abbasi, A and Ebrahimzadeh Leylabadlo, H and Sadeghi, J and Mehri, S and Naeimi Mazraeh, F and Feizi, H and Bannazadeh Baghi, H}, title = {Gut microbiota and obesity: an overview of microbiota to microbial-based therapies.}, journal = {Postgraduate medical journal}, volume = {99}, number = {1171}, pages = {384-402}, doi = {10.1136/postgradmedj-2021-141311}, pmid = {37294712}, issn = {1469-0756}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome/physiology ; Obesity/therapy ; *Probiotics/therapeutic use ; Prebiotics ; Body Weight ; }, abstract = {The increasing prevalence of obesity and overweight is a significant public concern throughout the world. Obesity is a complex disorder involving an excessive amount of body fat. It is not just a cosmetic concern. It is a medical challenge that increases the risk of other diseases and health circumstances, such as diabetes, heart disease, high blood pressure and certain cancers. Environmental and genetic factors are involved in obesity as a significant metabolic disorder along with diabetes. Gut microbiota (GM) has a high potential for energy harvesting from the diet. In the current review, we aim to consider the role of GM, gut dysbiosis and significant therapies to treat obesity. Dietary modifications, probiotics, prebiotics, synbiotics compounds, using faecal microbiota transplant, and other microbial-based therapies are the strategies to intervene in obesity reducing improvement. Each of these factors serves through various mechanisms including a variety of receptors and compounds to control body weight. Trial and animal investigations have indicated that GM can affect both sides of the energy-balancing equation; first, as an influencing factor for energy utilisation from the diet and also as an influencing factor that regulates the host genes and energy storage and expenditure. All the investigated articles declare the clear and inevitable role of GM in obesity. Overall, obesity and obesity-relevant metabolic disorders are characterised by specific modifications in the human microbiota's composition and functions. The emerging therapeutic methods display positive and promising effects; however, further research must be done to update and complete existing knowledge.}, }
@article {pmid37293229, year = {2023}, author = {Pargin, E and Roach, MJ and Skye, A and Papudeshi, B and Inglis, LK and Mallawaarachchi, V and Grigson, SR and Harker, C and Edwards, RA and Giles, SK}, title = {The human gut virome: composition, colonization, interactions, and impacts on human health.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {963173}, pmid = {37293229}, issn = {1664-302X}, abstract = {The gut virome is an incredibly complex part of the gut ecosystem. Gut viruses play a role in many disease states, but it is unknown to what extent the gut virome impacts everyday human health. New experimental and bioinformatic approaches are required to address this knowledge gap. Gut virome colonization begins at birth and is considered unique and stable in adulthood. The stable virome is highly specific to each individual and is modulated by varying factors such as age, diet, disease state, and use of antibiotics. The gut virome primarily comprises bacteriophages, predominantly order Crassvirales, also referred to as crAss-like phages, in industrialized populations and other Caudoviricetes (formerly Caudovirales). The stability of the virome's regular constituents is disrupted by disease. Transferring the fecal microbiome, including its viruses, from a healthy individual can restore the functionality of the gut. It can alleviate symptoms of chronic illnesses such as colitis caused by Clostridiodes difficile. Investigation of the virome is a relatively novel field, with new genetic sequences being published at an increasing rate. A large percentage of unknown sequences, termed 'viral dark matter', is one of the significant challenges facing virologists and bioinformaticians. To address this challenge, strategies include mining publicly available viral datasets, untargeted metagenomic approaches, and utilizing cutting-edge bioinformatic tools to quantify and classify viral species. Here, we review the literature surrounding the gut virome, its establishment, its impact on human health, the methods used to investigate it, and the viral dark matter veiling our understanding of the gut virome.}, }
@article {pmid37293210, year = {2023}, author = {Huang, L and Ma, Z and Ze, X and Zhao, X and Zhang, M and Lv, X and Zheng, Y and Liu, H}, title = {Gut microbiota decreased inflammation induced by chronic unpredictable mild stress through affecting NLRP3 inflammasome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1189008}, pmid = {37293210}, issn = {2235-2988}, mesh = {Rats ; Animals ; *Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Gastrointestinal Microbiome ; Brain/metabolism ; Inflammation ; Stress, Psychological ; }, abstract = {Dysbiosis of the gut microbiota is associated with the development of depression, but the underlying mechanism remains unclear. The aim of this study was to determine the relationship between microbiota and NLRP3 inflammasome induced by chronic unpredictable mild stress (CUMS). Fecal transplantation (FMT) experiment was conducted to elucidate the potential mechanism. Levels of NLRP3 inflammasome, microbiota, inflammatory factors and tight junction proteins were measured. CUMS stimulation significantly increased the levels of NLRP3, Caspase-1 and ASC in brain and colon(p<0.05), decreased the levels of tight junction proteins Occludin and ZO-1 (p<0.05). Interestingly, increased NLRP3 inflammasome and inflammatory cytokines and decreased tight junction proteins were found in antibiotic-treated (Abx) rats received CUMS rat fecal microbiota transplantation. Furthermore, fecal microbiota transplantation altered the microbiota in Abx rats, which partially overlapped with that of the donor rats. Importantly, probiotic administration amended the alteration of microbiota induced by CUMS treatment, then reduced the levels of NLRP3 inflammasome and inflammatory factors. In conclusion, these findings suggested that depression-like behaviors induced by CUMS stimulation were related to altered gut microbiota, broke the intestinal barrier, promoted the expression of NLRP3 inflammasome and elevated inflammation. Therefore, improving the composition of microbiota via probiotic can attenuate inflammation by amending the microbiota and suppressing the activation of NLRP3 inflammasome, which is considered as a novel therapeutic strategy for depression.}, }
@article {pmid37292211, year = {2023}, author = {Zheng, Q and Wang, S and Tian, X and Liu, W and Gao, P}, title = {Fecal microbiota transplantation confirmed that 919 Syrup reduced the ratio of erucamide to 5-AVAB in hippocampus to alleviate postpartum depression by regulating gut microbes.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1203015}, pmid = {37292211}, issn = {1664-3224}, mesh = {Humans ; Mice ; Female ; Animals ; *Depression, Postpartum/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Hippocampus ; }, abstract = {BACKGROUND: Postpartum depression has a crucial impact on the physical and psychological comfort and the work of postnatal women, the growth and development of infants and mental health in adulthood. Finding a safe and effective anti-postnatal depression drug is currently an important research goal in this field.<br><br>METHODS: In this study, the forced swimming test (FST) and tail suspension test (TST) were used to evaluated the depressive behaviors of mice, and the changes of metabolites and intestinal microflora in mice with postpartum depression were examined through non-target metabolomics and 16S RNA sequencing respectively.<br><br>RESULTS: We found that traditional Chinese medicine compound 919 Syrup could alleviate postpartum depression in mice and inhibit the elevated erucamide level in depressive hippocampus. However, mice treated with antibiotics were not sensitive to the anti-postnatal depression effect of 919 Syrup, and the level of 5-aminovaleric acid betaine (5-AVAB) in their hippocampus was significantly decreased. Transplanting fecal microflora treated with 919 Syrup could effectively improve the depressive behaviors of mice, upregulate the level of gut-derived 5-AVAB in the hippocampus, and downregulate the level of erucamide. Erucamide was significantly negatively correlated with increased Bacteroides in intestine after 919 Syrup treatment or fecal transplantation, and significantly positively correlated with Ruminococcaceae UCG-014 which was increased in feces of mice with postpartum depression. The increase of Bacteroides, Lactobacillus, and Ruminiclostridium in intestine after fecal transplantation had a clearly positive correlation with 5-AVAB.<br><br>CONCLUSION: In brief, 919 Syrup may downregulate the ratio of hippocampal metabolites erucamide to 5-AVAB by regulating intestinal flora to alleviate postpartum depression, laying a scientific foundation for future pathological research and development of therapeutic drugs for postpartum depression.}, }
@article {pmid37291901, year = {2024}, author = {Sugihara, N and Okada, Y and Tomioka, A and Ito, S and Tanemoto, R and Nishii, S and Mizoguchi, A and Inaba, K and Hanawa, Y and Horiuchi, K and Wada, A and Akita, Y and Higashiyama, M and Kurihara, C and Komoto, S and Tomita, K and Hokari, R}, title = {Probiotic Yeast from Miso Ameliorates Stress-Induced Visceral Hypersensitivity by Modulating the Gut Microbiota in a Rat Model of Irritable Bowel Syndrome.}, journal = {Gut and liver}, volume = {18}, number = {3}, pages = {465-475}, pmid = {37291901}, issn = {2005-1212}, mesh = {Animals ; *Irritable Bowel Syndrome/microbiology/therapy ; *Probiotics/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/physiology ; Male ; *Rats, Wistar ; Rats ; *Fecal Microbiota Transplantation/methods ; *Disease Models, Animal ; Humans ; Caco-2 Cells ; Stress, Psychological/complications ; Fermented Foods/microbiology ; }, abstract = {BACKGROUND/AIMS: Recent studies indicate that probiotics, which have attracted attention as a treatment for irritable bowel syndrome, affect intestinal homeostasis. In this study, we investigated whether Zygosaccharomyces sapae (strain I-6), a probiotic yeast isolated from miso (a traditional Japanese fermented food), could improve irritable bowel syndrome symptoms.<br><br>METHODS: Male Wistar rats were exposed to water avoidance stress (WAS). The number of defecations during WAS and the visceral hypersensitivity before and after WAS were evaluated using colorectal distension. Tight junction changes were assessed by Western blotting. Some rats were fed with strain I-6 or &#x3b2;-glucan from strain I-6. Changes in the intestinal microbiota were analyzed. The effect of fecal microbiota transplantation after WAS was evaluated similarly. Caco-2 cells were stimulated with interleukin-1&#x3b2; and tight junction changes were investigated after coculture with strain I-6.<br><br>RESULTS: The increased number of stool pellets and visceral hypersensitivity induced by WAS were suppressed by administering strain I-6. The decrease in tight junction protein occludin by WAS was reversed by the administration of strain I-6. &#x3b2;-Glucan from strain I-6 also suppressed those changes induced by WAS. In the rat intestinal microbiota, treatment with strain I-6 altered the &#x3b2;-diversity and induced changes in bacterial occupancy. Upon fecal microbiota transplantation, some symptoms caused by WAS were ameliorated.<br><br>CONCLUSIONS: These results suggest that traditional fermented foods such as miso in Japan are valuable sources of probiotic yeast candidates, which may be useful for preventing and treating stress-induced visceral hypersensitivity.}, }
@article {pmid37291807, year = {2023}, author = {Romo-Araiza, A and Picazo-Aguilar, RI and Griego, E and Márquez, LA and Galván, EJ and Cruz, Y and Fernández-Presas, AM and Chávez-Guerra, A and Rodríguez-Barrera, R and Azpiri-Cardós, AP and Rosas-Quintero, C and Jasso-Chávez, R and Borlongan, CV and Ibarra, A}, title = {Symbiotic Supplementation (E. faecium and Agave Inulin) Improves Spatial Memory and Increases Plasticity in the Hippocampus of Obese Rats: A Proof-of-Concept Study.}, journal = {Cell transplantation}, volume = {32}, number = {}, pages = {9636897231177357}, pmid = {37291807}, issn = {1555-3892}, mesh = {Rats ; Animals ; Male ; *Spatial Memory ; *Agave/metabolism ; Inulin/pharmacology/therapeutic use ; Rats, Sprague-Dawley ; Hippocampus/metabolism ; Neuronal Plasticity/physiology ; Receptors, N-Methyl-D-Aspartate/metabolism ; Maze Learning/physiology ; Obesity/therapy ; Dietary Supplements ; Inflammation ; }, abstract = {Obesity has been linked to cognitive impairment through systemic low-grade inflammation. High fat and sugar diets (HFSDs) also induce systemic inflammation, either by induced Toll-like receptor 4 response, or by causing dysbiosis. This study aimed to evaluate the effect of symbiotics supplementation on spatial and working memory, butyrate concentration, neurogenesis, and electrophysiological recovery of HFSD-fed rats. In a first experiment, Sprague-Dawley male rats were given HFSD for 10 weeks, after which they were randomized into 2 groups (n = 10 per group): water (control), or Enterococcus faecium + inulin (symbiotic) administration, for 5 weeks. In the fifth week, spatial and working memory was analyzed through the Morris Water Maze (MWM) and Eight-Arm Radial Maze (RAM) tests, respectively, with 1 week apart between tests. At the end of the study, butyrate levels from feces and neurogenesis at hippocampus were determined. In a second experiment with similar characteristics, the hippocampus was extracted to perform electrophysiological studies. Symbiotic-supplemented rats showed a significantly better memory, butyrate concentrations, and neurogenesis. This group also presented an increased firing frequency in hippocampal neurons [and a larger N-methyl-d-aspartate (NMDA)/α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) current ratio] suggesting an increase in NMDA receptors, which in turn is associated with an enhancement in long-term potentiation and synaptic plasticity. Therefore, our results suggest that symbiotics could restore obesity-related memory impairment and promote synaptic plasticity.}, }
@article {pmid37289890, year = {2023}, author = {Fidelle, M and Rauber, C and Alves Costa Silva, C and Tian, AL and Lahmar, I and de La Varende, AM and Zhao, L and Thelemaque, C and Lebhar, I and Messaoudene, M and Pizzato, E and Birebent, R and Mbogning Fonkou, MD and Zoppi, S and Reni, A and Dalban, C and Leduc, M and Ferrere, G and Durand, S and Ly, P and Silvin, A and Mulder, K and Dutertre, CA and Ginhoux, F and Yonekura, S and Roberti, MP and Tidjani-Alou, M and Terrisse, S and Chen, J and Kepp, O and Schippers, A and Wagner, N and Suárez-Gosálvez, J and Kobold, S and Fahrner, JE and Richard, C and Bosq, J and Lordello, L and Vitali, G and Galleron, N and Quinquis, B and Le Chatelier, E and Blanchard, L and Girard, JP and Jarry, A and Gervois, N and Godefroy, E and Labarrière, N and Koschny, R and Daillère, R and Besse, B and Truntzer, C and Ghiringhelli, F and Coatnoan, N and Mhanna, V and Klatzmann, D and Drubay, D and Albiges, L and Thomas, AM and Segata, N and Danlos, FX and Marabelle, A and Routy, B and Derosa, L and Kroemer, G and Zitvogel, L}, title = {A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers.}, journal = {Science (New York, N.Y.)}, volume = {380}, number = {6649}, pages = {eabo2296}, doi = {10.1126/science.abo2296}, pmid = {37289890}, issn = {1095-9203}, mesh = {Animals ; Humans ; Mice ; *Anti-Bacterial Agents/adverse effects ; Bacteria/immunology ; *Cell Adhesion Molecules/metabolism ; Cell Movement ; *Drug Resistance, Neoplasm ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; *Immune Checkpoint Inhibitors/therapeutic use ; *Immune Tolerance/drug effects ; *Immunologic Surveillance ; *Integrins/metabolism ; Interleukin-17/metabolism ; *Mucoproteins/metabolism ; *Neoplasms/immunology/therapy ; Th17 Cells/immunology ; Gastrointestinal Tract/immunology/microbiology ; }, abstract = {Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but the mechanisms underlying their immunosuppressive effects remain unknown. By inducing the down-regulation of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in the ileum, post-ABX gut recolonization by Enterocloster species drove the emigration of enterotropic α4β7[+]CD4[+] regulatory T 17 cells into the tumor. These deleterious ABX effects were mimicked by oral gavage of Enterocloster species, by genetic deficiency, or by antibody-mediated neutralization of MAdCAM-1 and its receptor, α4β7 integrin. By contrast, fecal microbiota transplantation or interleukin-17A neutralization prevented ABX-induced immunosuppression. In independent lung, kidney, and bladder cancer patient cohorts, low serum levels of soluble MAdCAM-1 had a negative prognostic impact. Thus, the MAdCAM-1-α4β7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.}, }
@article {pmid37287985, year = {2023}, author = {Chen, Y and Chen, J and Wei, H and Gong, K and Meng, J and Long, T and Guo, J and Hong, J and Yang, L and Qiu, J and Xiong, K and Wang, Z and Xu, Q}, title = {Akkermansia muciniphila-Nlrp3 is involved in the neuroprotection of phosphoglycerate mutase 5 deficiency in traumatic brain injury mice.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1172710}, pmid = {37287985}, issn = {1664-3224}, mesh = {Male ; Akkermansia ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism ; Phosphoglycerate Mutase ; Mice ; Verrucomicrobia/chemistry/metabolism ; Neuroinflammatory Diseases ; *Neuroprotection ; Animals ; *Brain Injuries, Traumatic/therapy/metabolism ; }, abstract = {INTRODUCTION: Gut-microbiota-brain axis is a potential treatment to decrease the risk of chronic traumatic encephalopathy following traumatic brain injury (TBI). Phosphoglycerate mutase 5 (PGAM5), a mitochondrial serine/threonine protein phosphatase, resides in mitochondrial membrane and regulates mitochondrial homeostasis and metabolism. Mitochondria mediates intestinal barrier and gut microbiome.<br><br>OBJECTIVES: This study investigated the association between PGAM5 and gut microbiota in mice with TBI.<br><br>METHODS: The controlled cortical impact injury was established in mice with genetically-ablated Pgam5 (Pgam5[-/-]) or wild type, and WT male mice were treated with fecal microbiota transplantation (FMT) from male Pgam5[-/-] mice or Akkermansia muciniphila (A. muciniphila). Then the gut microbiota abundance, blood metabolites, neurological function, and nerve injury were detected.<br><br>RESULTS: Treated with antibiotics for suppressing gut microbiota in Pgam5[-/-] mice partially relieved the role of Pgam5 deficiency in the improvement of initial inflammatory factors and motor dysfunction post-TBI. Pgam5 knockout exhibited an increased abundance of A. muciniphila in mice. FMT from male Pgam5[-/-] mice enabled better maintenance of amino acid metabolism and peripherial environment than that in TBI-vehicle mice, which suppressed neuroinflammation and improved neurological deficits, and A. muciniphila was negatively associated with intestinal mucosal injury and neuroinflammation post-TBI. Moreover, A. muciniphila treatment ameliorated neuroinflammation and nerve injury by regulating Nlrp3 inflammasome activation in cerebral cortex with TBI.<br><br>CONCLUSION: Thus, the present study provides evidence that Pgam5 is involved in gut microbiota-mediated neuroinflammation and nerve injury, with A. muciniphila-Nlrp3 contributing to peripheral effects.}, }
@article {pmid37286117, year = {2023}, author = {Song, S and Fan, M and Wen, X and Shi, X and Lou, Y and He, Z and Wen, C and Shao, T}, title = {Integrated network pharmacology and gut microbiome analysis to reveal the mechanism of Qu-Zhuo-Tong-Bi decoction against hyperuricemia and gout.}, journal = {Journal of ethnopharmacology}, volume = {316}, number = {}, pages = {116736}, doi = {10.1016/j.jep.2023.116736}, pmid = {37286117}, issn = {1872-7573}, mesh = {Mice ; Animals ; *Hyperuricemia/drug therapy ; *Gastrointestinal Microbiome ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; *Gout/drug therapy ; Cytokines ; TOR Serine-Threonine Kinases ; }, abstract = {Qu-zhuo-tong-bi decoction (QZTBD) is a classic Chinese herbal medicine that has shown therapeutic efficacy in clinical practice against hyperuricemia and gout. However, the potential mechanisms of QZTBD remain poorly investigated.<br><br>AIM OF THE STUDY: To assess the therapeutic effects of QZTBD on hyperuricemia and gout and to reveal its mechanisms of action.<br><br>MATERIALS AND METHODS: A Uox-KO mouse model of hyperuricemia and gout was established, and QZTBD was administered at a dosage of 18.0&#xa0;g/kg/d. Throughout the experimental period, the effects of QZTBD on gout symptoms were monitored and analyzed. The integrated network pharmacology and gut microbiota analysis strategy was conducted to explore the mechanism of QZTBD in the treatment of hyperuricemia and gout. Targeted metabolomic analysis was performed to investigate the variation of amino acids and Spearman's rank correlation analysis was conducted to reveal the relationship between the discrepant bacterial genera and the altered amino acid. Flow cytometry was utilized to analysis the proportion of Th17 and Treg cells, and the production of pro-inflammatory cytokines was measured by ELISA. qRT-PCR and Western blot assay were applied to detect the expression of mRNA and protein respectively. Autodock vina 1.1.2 was used to evaluate the docking interactions.<br><br>RESULTS: QZTBD treatment showed remarkable efficacy against hyperuricemia and gout with respect to attenuation of disease activity metrics through gut microbiome recovery and intestinal immune homeostasis. The administration of QZTBD significantly elevated the abundance of Allobaculum and Candidatus sacchairmonas, corrected the aberrant amino acid patterns, repaired the impaired intestinal barrier, restored the balance of Th17/Treg cells via PI3K-AKT-mTOR pathway, and reduced the levels of inflammatory cytokines such as IL-1&#x3b2;, IL-6, TNF-&#x3b1; and IL-17. Fecal microbiota transplantation from QZTBD treated mice demonstrated convincing evidence of efficacy and mechanism of QZTBD.<br><br>CONCLUSION: Taken together, our study explores the therapeutic mechanism of an effective herbal formula, QZTBD, for gout treatment through remodeling gut microbiome and regulating the differentiation of CD4[+] T cells via PI3K-AKT-mTOR pathway.}, }
@article {pmid37280255, year = {2023}, author = {Li, J and Feng, S and Wang, Z and He, J and Zhang, Z and Zou, H and Wu, Z and Liu, X and Wei, H and Tao, S}, title = {Limosilactobacillus mucosae-derived extracellular vesicles modulates macrophage phenotype and orchestrates gut homeostasis in a diarrheal piglet model.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {33}, pmid = {37280255}, issn = {2055-5008}, mesh = {Animals ; Swine ; Mice ; *Antidiarrheals ; Diarrhea/veterinary ; *Microbiota ; Lactobacillus ; Bacteria ; Escherichia coli ; Homeostasis ; }, abstract = {The diarrheal disease causes high mortality, especially in children and young animals. The gut microbiome is strongly associated with diarrheal disease, and some specific strains of bacteria have demonstrated antidiarrheal effects. However, the antidiarrheal mechanisms of probiotic strains have not been elucidated. Here, we used neonatal piglets as a translational model and found that gut microbiota dysbiosis observed in diarrheal piglets was mainly characterized by a deficiency of Lactobacillus, an abundance of Escherichia coli, and enriched lipopolysaccharide biosynthesis. Limosilactobacillus mucosae and Limosilactobacillus reuteri were a signature bacterium that differentiated healthy and diarrheal piglets. Germ-free (GF) mice transplanted with fecal microbiota from diarrheal piglets reproduced diarrheal disease symptoms. Administration of Limosilactobacillus mucosae but not Limosilactobacillus reuteri alleviated diarrheal disease symptoms induced by fecal microbiota of diarrheal piglets and by ETEC K88 challenge. Notably, Limosilactobacillus mucosae-derived extracellular vesicles alleviated diarrheal disease symptoms caused by ETEC K88 by regulating macrophage phenotypes. Macrophage elimination experiments demonstrated that the extracellular vesicles alleviated diarrheal disease symptoms in a macrophage-dependent manner. Our findings provide insights into the pathogenesis of diarrheal disease from the perspective of intestinal microbiota and the development of probiotic-based antidiarrheal therapeutic strategies.}, }
@article {pmid37279097, year = {2023}, author = {Zhu, R and Liu, L and Zhang, G and Dong, J and Ren, Z and Li, Z}, title = {The pathogenesis of gut microbiota in hepatic encephalopathy by the gut-liver-brain axis.}, journal = {Bioscience reports}, volume = {43}, number = {6}, pages = {}, pmid = {37279097}, issn = {1573-4935}, mesh = {Humans ; *Hepatic Encephalopathy/therapy/metabolism/microbiology ; *Gastrointestinal Microbiome ; Ammonia/metabolism ; *Hyperammonemia/therapy/metabolism ; Liver Cirrhosis/metabolism ; Fibrosis ; Brain/metabolism ; }, abstract = {Hepatic encephalopathy (HE) is a neurological disease occurring in patients with hepatic insufficiency and/or portal-systemic blood shunting based on cirrhosis. The pathogenesis is not completely clear till now, but it is believed that hyperammonemia is the core of HE. Hyperammonemia caused by increased sources of ammonia and decreased metabolism further causes mental problems through the gut-liver-brain axis. The vagal pathway also plays a bidirectional role in the axis. Intestinal microorganisms play an important role in the pathogenesis of HE through the gut-liver-brain axis. With the progression of cirrhosis to HE, intestinal microbial composition changes gradually. It shows the decrease of potential beneficial taxa and the overgrowth of potential pathogenic taxa. Changes in gut microbiota may lead to a variety of effects, such as reduced production of short-chain fatty acids (SCFAs), reduced production of bile acids, increased intestinal barrier permeability, and bacterial translocation. The treatment aim of HE is to decrease intestinal ammonia production and intestinal absorption of ammonia. Prebiotics, probiotics, antibiotics, and fecal microbiota transplantation (FMT) can be used to manipulate the gut microbiome to improve hyperammonemia and endotoxemia. Especially the application of FMT, it has become a new treated approach to target microbial composition and function. Therefore, restoring intestinal microbial homeostasis can improve the cognitive impairment of HE, which is a potential treatment method.}, }
@article {pmid37278910, year = {2023}, author = {Ha, MV and McCormick, TS and Salem, I and Al-Shakhshir, H and Ghannoum, MA and Carroll, BT}, title = {Skin and gut microbial associations with squamous cell carcinoma in solid organ transplant recipients.}, journal = {Archives of dermatological research}, volume = {315}, number = {9}, pages = {2709-2713}, pmid = {37278910}, issn = {1432-069X}, support = {P30 CA043703/CA/NCI NIH HHS/United States ; P30 CA043703/CA/NCI NIH HHS/United States ; P30 CA043703/CA/NCI NIH HHS/United States ; P30 CA043703/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Adolescent ; *Skin Neoplasms/epidemiology/pathology ; Case-Control Studies ; *Gastrointestinal Microbiome ; Pilot Projects ; *Carcinoma, Squamous Cell/epidemiology/etiology/pathology ; *Organ Transplantation/adverse effects/methods ; }, abstract = {Solid organ transplant recipients (SOTRs) are burdened with a significantly higher risk of squamous cell carcinoma (SCC) compared to the general population. Accumulating evidence suggests the potential influence of microbial dysbiosis on transplant outcomes. Based on these observations, we sought to identify differences in the cutaneous and gut microbiomes of SOTRs with and without a history of SCC. This case-control study collected and analyzed non-lesional skin and fecal samples of 20 SOTRs > 18 years old with either ≥ 4 diagnoses of SCC since most recent transplant (n = 10) or 0 diagnoses of SCC (n = 10). The skin and gut microbiomes were investigated with Next-Generation Sequencing, and analysis of variance (ANOVA) followed by Tukey pairwise comparison procedure was used to test for differences in taxonomic relative abundances and microbial diversity indices between the two cohorts. Analyses of the skin microbiome showed increased bacterial and reduced fungal diversity in SOTRs with a history of SCC compared to SOTRs without a history of SCC (bacterial median Shannon diversity index (SDI) = 3.636 and 3.154, p < 0.05; fungal SDI = 4.474 and 6.174, p < 0.05, respectively). Analyses of the gut microbiome showed reduced bacterial and fungal diversity in the SCC history cohort compared to the SCC history-negative cohort (bacterial SDI = 2.620 and 3.300, p < 0.05; fungal SDI = 3.490 and 3.812, p < 0.05, respectively). The results of this pilot study thus show a trend toward the bacterial and fungal communities of the gut and skin being distinct in SOTRs with a history of SCC compared to SOTRs without a history of SCC. It furthermore demonstrates the potential for microbial markers to be used in the prognostication of squamous cell carcinoma risk in solid organ transplant recipients.}, }
@article {pmid37278206, year = {2023}, author = {Li, R and Xu, S and Li, B and Zhang, B and Chen, W and Dai, D and Liu, Z}, title = {Gut indigenous Ruminococcus gnavus alleviates constipation and stress-related behaviors in mice with loperamide-induced constipation.}, journal = {Food &amp; function}, volume = {14}, number = {12}, pages = {5702-5715}, doi = {10.1039/d2fo03574j}, pmid = {37278206}, issn = {2042-650X}, mesh = {Mice ; Animals ; *Loperamide/adverse effects ; *Ruminococcus/genetics ; Constipation/chemically induced/drug therapy/microbiology ; Clostridiales ; Feces/microbiology ; }, abstract = {Refractory constipation is the most severe form of constipation, and its etiology remains unknown. The symptoms of constipation occur repeatedly, which brings great pain to the patient's body and psychology. Accumulating studies suggest that constipation patients present a significant dysbiosis of the gut microbiota compared with healthy individuals. In this study, we analyzed the gut microbiota composition of fresh feces and accumulated feces (old feces) of patients with refractory constipation and found that there was a significant difference between them. Through a mouse model of loperamide-induced constipation, it was proved that the old feces of patients with refractory constipation could aggravate the constipation symptoms in mice, while the fresh feces could alleviate the symptoms, which is consistent with the effect of feces from healthy volunteers in a mouse model of loperamide-induced constipation. We identified an indigenous strain Ruminococcus gnavus (R. gnavus), which is highly enriched in the fresh feces of patients with refractory constipation, and found that oral administration of R. gnavus could effectively improve the constipation symptoms in mice with constipation induced by loperamide and fecal bacteria transplanted from patients with constipation and significantly improve the stress-related behaviors of mice. This result may be related to the regulation of intestinal muc2, c-kit, sert and other gene expression by R. gnavus and the control of somatostatin (SS) and motilin (MTL) production. Our results suggest that gut microbe intervention with indigenous strains such as R. gnavus is a potential and promising alternative for the treatment of constipation, especially for refractory constipation.}, }
@article {pmid37278059, year = {2023}, author = {Liu, L and Wu, Q and Chen, Y and Ren, H and Zhang, Q and Yang, H and Zhang, W and Ding, T and Wang, S and Zhang, Y and Liu, Y and Sun, J}, title = {Gut microbiota in chronic pain: Novel insights into mechanisms and promising therapeutic strategies.}, journal = {International immunopharmacology}, volume = {115}, number = {}, pages = {109685}, doi = {10.1016/j.intimp.2023.109685}, pmid = {37278059}, issn = {1878-1705}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Chronic Pain/therapy ; Quality of Life ; *Neuralgia ; *Probiotics/therapeutic use ; }, abstract = {Chronic pain remains one of the world's most persistent and unsolved clinical challenges that severely affect patients' quality of life. Presently, considering that the mechanisms underlying chronic pain are not fully understood, there is a lack of effective drugs and interventions to treat chronic pain in clinical practice. Therefore, exploring the pathogenic mechanism of chronic pain and establishing potential targets are the keys to treating chronic pain. Substantial evidence has indicated that gut microbiota plays a crucial role in modulating chronic pain, which has opened up a new frontier for investigating the pathogenesis of chronic pain. The gut microbiota is a pivotal junction point between the neuroimmune-endocrine and the microbiome-gut-brain axes that could directly or indirectly affect chronic pain. Different signaling molecules (such as metabolites, neuromodulators, neuropeptides, and neurotransmitters) from the gut microbiota regulate the progress of chronic pain by modulating the peripheral and central sensitization by targeting the corresponding receptors. Furthermore, gut microbiota dysbiosis is associated with the progress of different chronic pain disorders, such as visceral pain, neuropathic pain, inflammatory pain, migraine, and fibromyalgia. Therefore, the present review attempted to systematically summarize the action of the gut microbiota toward regulating the pathological mechanisms of chronic pain and discussed the beneficial effects of probiotics supplementation or fecal microbiota transplantation (FMT) to restore the gut microbiota in chronic pain patients so as to provide a new strategy for targeting the gut microbiota for alleviating chronic pain issues.}, }
@article {pmid37276766, year = {2023}, author = {Lund, MC and Larsen, BB and Rowsey, DM and Otto, HW and Gryseels, S and Kraberger, S and Custer, JM and Steger, L and Yule, KM and Harris, RE and Worobey, M and Van Doorslaer, K and Upham, NS and Varsani, A}, title = {Using archived and biocollection samples towards deciphering the DNA virus diversity associated with rodent species in the families cricetidae and heteromyidae.}, journal = {Virology}, volume = {585}, number = {}, pages = {42-60}, doi = {10.1016/j.virol.2023.05.006}, pmid = {37276766}, issn = {1096-0341}, mesh = {Animals ; *Rodentia ; Phylogeny ; DNA Viruses/genetics ; *Viruses/genetics ; Mammals ; Genome, Viral ; }, abstract = {Rodentia is the most speciose order of mammals, and they are known to harbor a wide range of viruses. Although there has been significant research on zoonotic viruses in rodents, research on the diversity of other viruses has been limited, especially for rodents in the families Cricetidae and Heteromyidae. In fecal and liver samples of nine species of rodents, we identify 346 distinct circular DNA viral genomes. Of these, a large portion are circular, single-stranded DNA viruses in the families Anelloviridae (n = 3), Circoviridae (n = 5), Genomoviridae (n = 7), Microviridae (n = 297), Naryaviridae (n = 4), Vilyaviridae (n = 15) and in the phylum Cressdnaviricota (n = 13) that cannot be assigned established families. We also identified two large bacteriophages of 36 and 50 kb that are part of the class Caudoviricetes. Some of these viruses are clearly those that infect rodents, however, most of these likely infect various organisms associated with rodents, their environment or their diet.}, }
@article {pmid37275867, year = {2023}, author = {Wang, M and Xie, X and Zhao, S and Ma, X and Wang, Z and Zhang, Y}, title = {Fecal microbiota transplantation for irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1136343}, pmid = {37275867}, issn = {1664-3224}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy ; Fecal Microbiota Transplantation/adverse effects ; Randomized Controlled Trials as Topic ; Feces ; *Gastrointestinal Microbiome/physiology ; }, abstract = {OBJECTIVE: Whether fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS) is effective in improving outcomes remains controversial. We assessed the safety and efficacy of FMT for patients with IBS.<br><br>METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, the Cochrane Library, the clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP) up to February 25, 2022, updated to March 28, 2023. Randomized controlled trials (RCTs) compared the stool and capsule FMT with placebo in patients with IBS were included. Two authors independently assessed study eligibility, extracted the data, and assessed risk of bias. We did meta-analysis with RevMan, and the Stata software was used for sensitivity analysis and meta-regression. The GRADE system was used to assess the quality of evidences. Mean difference (MD) or standardized Mean difference (SMD) with 95% CI for continuous data, and risk ratios (RR) with 95% CI for dichotomous data were used with random-effects models. The primary outcomes included the clinical response rate and IBS-SSS score. This study is registered with PROSPERO: CRD42022328377.<br><br>RESULTS: Nineteen reports from nine RCTs were included finally. Compared with the placebo, a single stool FMT could significantly decrease the IBS-SSS score at 1 month (MD=-65.75, 95%CI [-129.37, -2.13]), 3 months (MD=-102.11, 95% CI [-141.98, -62.24]), 6 months (MD=-84.38, 95%CI [-158.79, -9.97]), 24 months (MD=-110.41, 95%CI [-145.37, -75.46]), and 36 months (MD=-104.71, 95%CI [-137.78, -71.64]). It also could improve the clinical response rate at 3 months (RR=1.91, 95% [1.12, 3.25]), 24 months (RR=2.97, 95% [1.94, 4.54]), and 36 months (RR=2.48, 95% [1.65, 3.72]), and increase the IBS-QoL score at 3 months, 24 months, and 36 months. FMT did not increase the serious adverse event. The risk of bias was low, and the quality of evidence based on GRADE system was moderate in the stool FMT group. However, we did not find positive effect of capsule FMT on patients with IBS based on the current available data.<br><br>CONCLUSION: A single stool FMT is effective and safe for patients with IBS. However, some factors may affect the effectiveness of FMT, and the relationship between the gut microbiome and the effect of FMT for IBS is still unclear.<br><br>https://www.crd.york.ac.uk/prospero/, identifier CRD42022328377.}, }
@article {pmid37275381, year = {2023}, author = {García-Mateo, S and Lanas, A}, title = {Editorial: Improving the gut microbiome: applications of fecal transplantation in disease.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1203448}, doi = {10.3389/fmed.2023.1203448}, pmid = {37275381}, issn = {2296-858X}, }
@article {pmid37275140, year = {2023}, author = {Bao, Z and Wei, R and Zheng, X and Zhang, T and Bi, Y and Shen, S and Zou, P and Zhang, J and Yan, H and Li, MD and Yang, Z and Gao, H}, title = {Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1185993}, pmid = {37275140}, issn = {1664-302X}, abstract = {INTRODUCTION: Submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant) is a likely characteristic pathological feature of ACLF in patients with hepatitis B cirrhosis. We aimed to comprehensively explore microbiome and bile acids patterns across enterhepatic circulation and build well-performing machine learning models to predict SMHN status.<br><br>METHODS: Based on the presence or absence of SMHN, 17 patients with HBV-related end-stage liver disease who received liver transplantation were eligible for inclusion. Serum, portal venous blood, and stool samples were collected for comparing differences of BA spectra and gut microbiome and their interactions. We adopted the random forest algorithm with recursive feature elimination (RF-RFE) to predict SMHN status.<br><br>RESULTS: By comparing total BA spectrum between SMHN (-) and SMHN (+) patients, significant changes were detected only in fecal (P = 0.015). Compared with the SMHN (+) group, the SMHN (-) group showed that UDCA, 7-KLCA, 3-DHCA, 7-KDCA, ISOLCA and &#x3b1;-MCA in feces, r-MCA, 7-KLCA and 7-KDCA in serum, &#x3b3;-MCA and 7-KLCA in portal vein were enriched, and TUDCA in feces was depleted. PCoA analysis showed significantly distinct overall microbial composition in two groups (P = 0.026). Co-abundance analysis showed that bacterial species formed strong and broad relationships with BAs. Among them, Parabacteroides distasonis had the highest node degree. We further identified a combinatorial marker panel with a high AUC of 0.92.<br><br>DISCUSSION: Our study demonstrated the changes and interactions of intestinal microbiome and BAs during enterohepatic circulation in ACLF patients with SMHN. In addition, we identified a combinatorial marker panel as non-invasive biomarkers to distinguish the SMHN status with high AUC.}, }
@article {pmid37274526, year = {2023}, author = {Crump, JA and Nyirenda, TS and Kalonji, LM and Phoba, MF and Tack, B and Platts-Mills, JA and Gordon, MA and Kariuki, SM}, title = {Nontyphoidal Salmonella Invasive Disease: Challenges and Solutions.}, journal = {Open forum infectious diseases}, volume = {10}, number = {Suppl 1}, pages = {S32-S37}, pmid = {37274526}, issn = {2328-8957}, support = {R01 AI099525/AI/NIAID NIH HHS/United States ; R01 AI121378/AI/NIAID NIH HHS/United States ; }, abstract = {Nontyphoidal Salmonella are a leading cause of community-onset bacteremia and other serious infections in sub-Saharan African countries where large studies indicate that they are an uncommon cause of moderate-to-severe diarrhea. Approximately 535 000 nontyphoidal Salmonella invasive disease illnesses and 77 500 deaths were estimated to occur in 2017; 422 000 (78.9%) illnesses and 66 500 (85.9%) deaths in countries in sub-Saharan Africa. Lineages of Salmonella enterica serovar Typhimurium sequence type (ST) 313 and lineages of Salmonella enterica serovar Enteritidis ST11 dominate as causes of invasive disease. A major reservoir for these specific strains outside of humans has not been identified to date. Human fecal shedding of such strains is common in areas where nontyphoidal Salmonella invasive disease incidence is high. The case-fatality ratio of nontyphoidal Salmonella invasive disease is approximately 15%. Early diagnosis and treatment are needed to avert fatal outcomes. Antimicrobial resistance, including multiple drug resistance, decreased fluoroquinolone susceptibility, and resistance to third-generation cephalosporins, is increasing in prevalence and is likely to further compromise patient outcomes. Naturally acquired immunity against invasive disease develops in children aged >3 years in endemic areas, likely mediated in part by the sequential acquisition of T-cell immunity, followed by antigen-specific immunoglobulin G antibodies. Vaccines in preclinical or clinical development include live-attenuated S. enterica serovar Typhimurium, nontyphoidal S. enterica core and O-polysaccharide glycoconjugates, multiple antigen-presenting system complexes, and generalized modules for membrane antigens vaccines. The latter are in phase I trials in Europe and Africa. Both vaccine use, and other effective, evidence-based nonvaccine interventions, are needed to prevent and control nontyphoidal Salmonella invasive disease.}, }
@article {pmid37274301, year = {2023}, author = {Tariq, R and Pardi, DS and Khanna, S}, title = {Resolution rates in clinical trials for microbiota restoration for recurrent Clostridioides difficile infection: an updated systematic review and meta-analysis.}, journal = {Therapeutic advances in gastroenterology}, volume = {16}, number = {}, pages = {17562848231174293}, pmid = {37274301}, issn = {1756-283X}, abstract = {BACKGROUND: Microbiota restoration is highly effective to treat recurrent Clostridioides difficile infection (CDI) in observational studies (cure rates >90%) but efficacy in controlled clinical trials appears to be lower.<br><br>OBJECTIVES: To perform an updated meta-analysis to assess the efficacy of microbiota restoration for recurrent CDI in open-label registered prospective clinical trials compared to randomized controlled trials (RCTs).<br><br>DESIGN: A systematic review and meta-analysis was conducted.<br><br>DATA SOURCES AND METHODS: A systematic search of various databases was performed up to July 2022 to identify studies of interest. Clinical trials of microbiota restoration for recurrent CDI with clinical resolution with one dose were included. We calculated weighted pooled rates (WPRs) with 95% confidence intervals (CIs).<br><br>RESULTS: In all, 19 clinical trials with 1176 recurrent CDI patients were included. Of the patients treated with microbiota restoration, 897 experienced a clinical cure with a single microbiota restoration therapy (WPR, 78%; 95% CI, 71-85%). There was significant heterogeneity among studies with an I[2] of 88%. Analysis of trials with a control arm (non-microbiota restoration) revealed CDI resolution in 373 of 523 patients (WPR, 72%; 95% CI, 60-82%) with microbiota restoration. Among the nine open-label clinical trials, CDI resolution was seen in 524 of 653 patients after initial microbiota restoration (WPR, 84%; 95% CI, 74-92%). Comparison of resolution rates between RCTs and open-label trials revealed a lower cure rate in RCTs compared to open-label trials (WPR, 73 versus 84%, p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSIONS: Microbiota restoration in a randomized controlled setting leads to lower resolution rates compared to open label and observational settings, likely due to stricter definitions and inclusion criteria. Resolution rates in open-label studies were similar to observational studies.}, }
@article {pmid37272879, year = {2023}, author = {Huang, J and Zhou, H and Song, T and Wang, B and Ge, H and Zhang, D and Shen, P and Qiu, X and Li, H}, title = {Fecal microbiota transplantation from sodium alginate-dosed mice and normal mice mitigates intestinal barrier injury and gut dysbiosis induced by antibiotics and cyclophosphamide.}, journal = {Food &amp; function}, volume = {14}, number = {12}, pages = {5690-5701}, doi = {10.1039/d3fo01193c}, pmid = {37272879}, issn = {2042-650X}, mesh = {Animals ; Mice ; *Fecal Microbiota Transplantation ; Dysbiosis/chemically induced/therapy/metabolism ; Intestinal Mucosa/metabolism ; *Intestinal Diseases/metabolism ; Inflammation/metabolism ; Toll-Like Receptors/metabolism ; }, abstract = {This study investigated the protective properties of fecal microbiota derived from mice treated with sodium alginate (SA) and normal mice with both types immunosuppressed by exposure to antibiotics and cyclophosphamide. A dietary intervention using SA obviously increased the diversity and improved the composition of gut microbiota in normal mice. Fecal microbiota transfer (FMT) from both mice treated with sodium alginate and normal mice alleviated spleen tissue damage and improved immune function. FMT alleviated intestinal mucosal injury and reduced intestinal permeability via increasing mucin and tight junction protein expression. In addition, FMT reduced gut inflammation via down-regulating the expression of toll-like receptor 4 protein. Furthermore, FMT treatment improved the disordered gut microbiota via increasing the abundance of Lactobacillus and Lachnospiraceae NK4A136 group whilst decreasing the abundance of Bacteroides. PICRUSt2 function prediction analysis showed that, compared with the model group, FMT treatment significantly down-regulated lipopolysaccharide biosynthesis and the mitogen-activated protein kinase signaling pathway-fly. Collectively, we found that SA can regulate the gut microbiota structure of normal mice and confirms the effectiveness of FMT in alleviating intestinal barrier damage and gut dysbiosis in antibiotic-cyclophosphamide-induced immunosuppressed mice. This work also reveals that SA can potentially alleviate the immunosuppression caused by cyclophosphamide in mice by modulating the intestinal microbiota and exploiting their functional properties.}, }
@article {pmid37269894, year = {2023}, author = {Zhang, S and Zhao, T and Wang, Y and Mi, J and Liu, J and Fan, X and Niu, R and Sun, Z}, title = {Intestinal microbiota regulates colonic inflammation in fluorosis mice by TLR/NF-κB pathway through short-chain fatty acids.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {178}, number = {}, pages = {113866}, doi = {10.1016/j.fct.2023.113866}, pmid = {37269894}, issn = {1873-6351}, mesh = {Mice ; Animals ; NF-kappa B/metabolism ; Signal Transduction ; *Gastrointestinal Microbiome ; Fluorides/toxicity ; Toll-Like Receptor 4/metabolism ; Inflammation ; *Intestinal Diseases ; Colon/metabolism ; Fatty Acids, Volatile ; }, abstract = {Intestinal inflammation and microbial dysbiosis are found simultaneously in patients with fluorosis. However, whether the inflammation derived from fluoride exposure only or intestinal microbial disorders has not been clarified. In this study, 100 mg/L NaF exposure for 90 days significantly elevated the expressions of inflammatory factors (TNF-α, IL-1β, IL-6, IFN-γ, TGF-β, and IL-10), and the levels of TLR4, TRAF6, Myd88, IKKβ, and NF-κB P65 in mouse colon, while the above factors were reduced in pseudo germ-free mice with fluorosis, hinting that disordered microbiota might play a more direct role in the development of colonic inflammation than fluoride. Fecal microbiota transplantation (FMT) lowered the levels of inflammatory factors and inactivated the TLR/NF-κB pathway in fluoride-exposed mice. In addition, supplementing short-chain fatty acids (SCFAs) exhibited the identical effects to the model of FMT. In summary, intestinal microbiota may alleviate the colonic inflammatory of mice with fluorosis by regulating TLR/NF-κB pathway through SCFAs.}, }
@article {pmid37265903, year = {2023}, author = {Duhan, S and Keisham, B and Salim, A}, title = {Fulminant Clostridioides difficile Colitis With SARS-CoV-2 Infection.}, journal = {Cureus}, volume = {15}, number = {5}, pages = {e38401}, pmid = {37265903}, issn = {2168-8184}, abstract = {Clostridioides difficile (C. difficile)and coronavirus disease 2019 (COVID-19) infections can have overlapping symptoms. Recently, the association and outcomes of coinfection have been studied. We present the case of an 83-year-old lady with Parkinson's disease (PD) who was admitted with pneumonia secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. She was treated with empiric antibiotics ampicillin-sulbactam and azithromycin, along with antiviral therapy remdesivir and baricitinib, and dexamethasone. The patient developed severe C. difficile infection with a leukemoid reaction. She was treated with intravenous metronidazole and oral vancomycin without any improvement. Before she could receive a fecal microbiota transplant, her infection progressed to fulminant colitis, and she required emergent surgery. The patient developed several complications post-surgery and succumbed to the severe illness. Our patient's multiple comorbidities and an underlying COVID-19 infection predisposed her to severe illness. This case emphasizes the long-standing discussion on antibiotic stewardship and encourages a debate on the role of immunosuppressant antiviral medications and underlying PD in predisposing patients to a severe C. difficile infection.}, }
@article {pmid37265797, year = {2023}, author = {Zha, C and Peng, Z and Huang, K and Tang, K and Wang, Q and Zhu, L and Che, B and Li, W and Xu, S and Huang, T and Yu, Y and Zhang, W}, title = {Potential role of gut microbiota in prostate cancer: immunity, metabolites, pathways of action?.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1196217}, pmid = {37265797}, issn = {2234-943X}, abstract = {The gut microbiota helps to reveal the relationship between diseases, but the role of gut microbiota in prostate cancer (PCa) is still unclear. Recent studies have found that the composition and abundance of specific gut microbiota are significantly different between PCa and non-PCa, and the gut microbiota may have common and unique characteristics between different diseases. Intestinal microorganisms are affected by various factors and interact with the host in a variety of ways. In the complex interaction model, the regulation of intestinal microbial metabolites and the host immune system is particularly important, and they play a key role in maintaining the ecological balance of intestinal microorganisms and metabolites. However, specific changes in the composition of intestinal microflora may promote intestinal mucosal immune imbalance, leading to the formation of tumors. Therefore, this review analyzes the immune regulation of intestinal flora and the production of metabolites, as well as their effects and mechanisms on tumors, and briefly summarizes that specific intestinal flora can play an indirect role in PCa through their metabolites, genes, immunity, and pharmacology, and directly participate in the occurrence, development, and treatment of tumors through bacterial and toxin translocation. We also discussed markers of high risk PCa for intestinal microbiota screening and the possibility of probiotic ingestion and fecal microbiota transplantation, in order to provide better treatment options for clinic patients. Finally, after summarizing a number of studies, we found that changes in immunity, metabolites.}, }
@article {pmid37265220, year = {2023}, author = {Alhobayb, T and Ciorba, MA}, title = {Clostridium difficile in inflammatory bowel disease.}, journal = {Current opinion in gastroenterology}, volume = {39}, number = {4}, pages = {257-262}, pmid = {37265220}, issn = {1531-7056}, support = {P30 DK052574/DK/NIDDK NIH HHS/United States ; R01 AI167285/AI/NIAID NIH HHS/United States ; T32 DK007130/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Child ; Humans ; *Clostridioides difficile ; Recurrence ; *Inflammatory Bowel Diseases/therapy/drug therapy ; *Crohn Disease/complications ; *Colitis, Ulcerative/complications ; *Clostridium Infections/diagnosis/epidemiology/therapy ; Fecal Microbiota Transplantation/methods ; *Colonic Diseases/complications ; }, abstract = {PURPOSE OF REVIEW: The chronic inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis, are associated with an increased risk of symptomatic Clostridium difficile infection (CDI). CDI may also masquerade as an IBD flare and complicate IBD management. This review provides a comprehensive overview of the epidemiology, diagnosis, and treatment of CDI in IBD patients.<br><br>RECENT FINDINGS: CDI remains common in IBD with complications including flares in disease activity, recurrent CDI episodes, and prolonged hospital stays. Newer IBD therapeutics including vedolizumab, ustekinumab, and tofacitinib are less likely to cause severe CDI. A high index of suspicion, rapid testing via a two-step method, and prompt treatment with vancomycin or fidaxomicin are paramount to managing CDI in IBD patients. Strategies to prevent recurrent CDI (rCDI) include the monoclonal antibody bezlotoxumab as well as fecal microbiota transplantation (FMT). FMT has a robust profile of safety and effectiveness in preventing rCDI in adults and children.<br><br>SUMMARY: Clinicians must remain vigilant in the prompt diagnosis and treatment of CDI in IBD patients. Corticosteroids, unnecessary antibiotics, and ongoing colonic inflammatory disease are modifiable risk factors. Improved infection control measures, newer IBD medications, and using effective CDI treatments will facilitate a reduced burden of severe CDI and complications for IBD patients.}, }
@article {pmid37264259, year = {2023}, author = {Zurek-Leffers, FM and Lehmann, F and Brabenec, L and Kintrup, S and Hellenthal, KEM and Mersjann, K and Kneifel, F and Hessler, M and Arnemann, PH and Kampmeier, TG and Ertmer, C and Kellner, P and Wagner, NM}, title = {A model of porcine polymicrobial septic shock.}, journal = {Intensive care medicine experimental}, volume = {11}, number = {1}, pages = {31}, pmid = {37264259}, issn = {2197-425X}, support = {WA3786/3-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs.<br><br>MATERIALS AND METHODS: The literature search was performed using the keywords "pig", "sepsis" and "septic shock". For the establishment of septic shock in n&#x2009;=&#x2009;10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3&#xa0;g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA.<br><br>RESULTS: Published porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8&#x2009;&#xb1;&#x2009;0.29&#xa0;h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54&#x2009;&#xb1;&#x2009;1&#xa0;mmHg) and significant hyperlactatemia (3.76&#x2009;&#xb1;&#x2009;0.65&#xa0;mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred.<br><br>CONCLUSIONS: We here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.}, }
@article {pmid37263544, year = {2023}, author = {Sumiyoshi, A and Fujii, H and Okuma, Y}, title = {Targeting microbiome, drug metabolism, and drug delivery in oncology.}, journal = {Advanced drug delivery reviews}, volume = {199}, number = {}, pages = {114902}, doi = {10.1016/j.addr.2023.114902}, pmid = {37263544}, issn = {1872-8294}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; *Neoplasms/drug therapy ; Immunity ; Tumor Microenvironment ; }, abstract = {Recent emerging scientific evidence shows a relationship between gut microbiota (GM) and immunomodulation. In the recently published "Hallmarks of Cancer", the microbiome has been reported to play a crucial role in cancer research, and perspectives for its clinical implementation to improve the effectiveness of pharmacotherapy were explored. Several studies have shown that GM can affect the outcomes of pharmacotherapy in cancer, suggesting that GM may affect anti-tumor immunity. Thus, studies on GM that analyze big data using computer-based analytical methods are required. In order to successfully deliver GM to an environment conducive to the proliferation of immune cells both within and outside the tumor microenvironment (TME), it is crucial to address a variety of challenges associated with distinct delivery methods, specifically those pertaining to oral, endoscopic, and intravenous delivery. Clinical trials are in progress to evaluate the effects of targeting GM and whether it can enhance immunity or act on the TME, thereby to improve the clinical outcomes for cancer patients.}, }
@article {pmid37261348, year = {2023}, author = {Singh, A and Alexander, SG and Martin, S}, title = {Gut microbiome homeostasis and the future of probiotics in cancer immunotherapy.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1114499}, pmid = {37261348}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Neoplasms ; Immunotherapy ; Prebiotics ; }, abstract = {The gut microbiome has an impact on cancer immune surveillance and immunotherapy, with recent studies showing categorical differences between immunotherapy-sensitive and immunotherapy-resistant cancer patient cohorts. Although probiotics are traditionally being supplemented to promote treatments or sustain therapeutic benefits; the FDA has not approved any for use with immunotherapy. The first step in developing probiotics for immunotherapy is identifying helpful or harmful bacteria down to the strain level. The gut microbiome's heterogeneity before and during treatment is also being investigated to determine microbial strains that are important for immunotherapy. Moreover, Dietary fiber intake, prebiotic supplementation and fecal microbiota transplantation (FMT) were found to enhance intratumoral CD8+ T cell to T-reg ratio in the clinics. The possibility of probiotic immunotherapy as a "living adjuvant" to CAR treatment and checkpoint blockade resistance is actively being investigated.}, }
@article {pmid37258604, year = {2023}, author = {Sugita, K and Shima, A and Takahashi, K and Ishihara, G and Kawano, K and Ohmori, K}, title = {Pilot evaluation of a single oral fecal microbiota transplantation for canine atopic dermatitis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {8824}, pmid = {37258604}, issn = {2045-2322}, mesh = {Animals ; Dogs ; *Dermatitis, Atopic/veterinary/drug therapy ; *Dog Diseases/pathology ; Fecal Microbiota Transplantation ; Pilot Projects ; Pruritus/veterinary ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The gut microbiota has been suggested to be involved in the pathogenesis of canine atopic dermatitis (cAD). However, the gut microbiota has not been well characterized in dogs with atopic dermatitis (AD). In addition, the efficacy of fecal microbiota transplantation (FMT) in dogs with AD remains unclear. This research, therefore, aimed to characterize the gut microbiota of dogs with AD and conduct pilot evaluation of the efficacy of a single oral FMT on clinical signs and the gut microbiota of dogs with AD. For these purposes, we used 12 dogs with AD and 20 healthy dogs. The 16S rRNA analysis of the fecal microbiota revealed significant differences between 12 dogs with AD and 20 healthy dogs. Next, a single oral FMT was performed in 12 dogs with AD as a single-arm, open-label clinical trial for 56 days. A single oral FMT significantly decreased Canine Atopic Dermatitis Extent and Severity Index (CADESI)-04 scores from day 0 (median score, 16.5) to day 56 (8) and Pruritus Visual Analog Scale (PVAS) scores from days 0 (median score, 3) to day 56 (1). Furthermore, a single oral FMT changed the composition of the fecal microbiota of dogs with AD at the phylum and genus levels. The number of common amplicon sequence variants in the fecal microbiota between donor dogs and dogs with AD was positively correlated with CADESI-04 and PVAS reduction ratios 56 days after FMT. Our findings suggest that the gut microbiota plays a pivotal role in the pathogenesis of cAD, and that oral FMT could be a new therapeutic approach targeting the gut microbiota in cAD.}, }
@article {pmid37258543, year = {2023}, author = {Liu, J and Sun, J and Yu, J and Chen, H and Zhang, D and Zhang, T and Ma, Y and Zou, C and Zhang, Z and Ma, L and Yu, X}, title = {Gut microbiome determines therapeutic effects of OCA on NAFLD by modulating bile acid metabolism.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {29}, pmid = {37258543}, issn = {2055-5008}, mesh = {Mice ; Animals ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; *Gastrointestinal Microbiome ; Chenodeoxycholic Acid/pharmacology/therapeutic use ; Bile Acids and Salts ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, had no approved pharmacological agents yet. Obeticholic acid (OCA), a novel bile acid derivative, was demonstrated to ameliorate NAFLD-related manifestations. Regarding the role of gut-liver axis in liver disease development, this study aimed to explore the potential role of gut microbiota in the treatment of OCA in NAFLD mice induced by the high-fat diet (HFD). Antibiotic-induced microbiome depletion (AIMD) and fecal microbiota transplantation (FMT) confirmed the critical role of gut microbiota in OCA treatment for NAFLD by effectively alleviating histopathological lesions and restoring liver function impaired by HFD. Metagenomic analysis indicated that OCA intervention in HFD mice remarkably increased the abundance of Akkermansia muciniphila, Bifidobacterium spp., Bacteroides spp., Alistipes spp., Lactobacillus spp., Streptococcus thermophilus, and Parasutterella excrementihominis. Targeted metabolomics analysis indicated that OCA could modulate host bile acids pool by reducing levels of serum hydrophobic cholic acid (CA) and chenodeoxycholic acid (CDCA), and increasing levels of serum-conjugated bile acids, such as taurodeoxycholic acid (TDCA) and tauroursodesoxycholic acid (TUDCA) in the HFD-fed mice. Strong correlations were observed between differentially abundant microbes and the shifted bile acids. Furthermore, bacteria enriched by OCA intervention exhibited much greater potential in encoding 7alpha-hydroxysteroid dehydrogenase (7α-HSDs) producing secondary bile acids rather than bile salt hydrolases (BSHs) mainly responsible for primary bile acid deconjugation. In conclusion, this study demonstrated that OCA intervention altered gut microbiota composition with specially enriched gut microbes modulating host bile acids, thus effectively alleviating NAFLD in the mice.}, }
@article {pmid37257477, year = {2023}, author = {Schönherr, S and Jung, L and Lübbert, C}, title = {[Clostridioides difficile - New Insights and Therapy Recommendations].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {148}, number = {12}, pages = {752-758}, doi = {10.1055/a-1970-9211}, pmid = {37257477}, issn = {1439-4413}, mesh = {Humans ; Aged ; Vancomycin/therapeutic use ; *Clostridioides difficile ; Clostridioides ; Anti-Bacterial Agents/therapeutic use ; Fidaxomicin/therapeutic use ; *Clostridium Infections/drug therapy/epidemiology ; }, abstract = {After an increase in Clostridioides difficile infections (CDI) until 2013 due to epidemic ribotypes such as 027 and 078, CDI incidence in Germany is now declining, as confirmed by recent epidemiological data. Despite this success through antimicrobial stewardship and hospital hygiene, the burden of disease remains high, especially in older patients (>65 years) with comorbidities. The main risk factor for CDI is the use of broad-spectrum antibiotics, which disrupt the gut microbiota, allowing C. difficile colonization. Coinfection with other intestinal pathogens such as enterococci can further increase the virulence of C. difficile. The updated 2021 ESCMID guidelines recommend fidaxomicin instead of vancomycin as the antibiotic of choice for the treatment of CDI because of its lower recurrence rate. Vancomycin remains a good alternative; however, metronidazole should only be used if neither antibiotic is available. In the future, ridinilazole may be available as another therapeutic option that has a narrow spectrum of activity and low intestinal absorption. For the treatment of recurrent CDI, the new guidelines also include the use of the monoclonal antibody bezlotoxumab. In addition, a new oral microbiome therapy, SER-109 (capsules containing purified Firmicutes spores), which showed promising results in a phase 3 study, may provide an easy-to-administer alternative to fecal microbiota transplantation. Hopes for a well-performing toxoid vaccine for primary and secondary prevention of CDI have unfortunately not been fulfilled in the CLOVER trial.}, }
@article {pmid37256150, year = {2023}, author = {Ben-Azu, B and Del Re, EC and VanderZwaag, J and Carrier, M and Keshavan, M and Khakpour, M and Tremblay, M&#xc8;}, title = {Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1139357}, pmid = {37256150}, issn = {1662-5102}, support = {R01 MH096942/MH/NIMH NIH HHS/United States ; }, abstract = {Brain aging, which involves a progressive loss of neuronal functions, has been reported to be premature in probands affected by schizophrenia (SCZ). Evidence shows that SCZ and accelerated aging are linked to changes in epigenetic clocks. Recent cross-sectional magnetic resonance imaging analyses have uncovered reduced brain reserves and connectivity in patients with SCZ compared to typically aging individuals. These data may indicate early abnormalities of neuronal function following cyto-architectural alterations in SCZ. The current mechanistic knowledge on brain aging, epigenetic changes, and their neuropsychiatric disease association remains incomplete. With this review, we explore and summarize evidence that the dynamics of gut-resident bacteria can modulate molecular brain function and contribute to age-related neurodegenerative disorders. It is known that environmental factors such as mode of birth, dietary habits, stress, pollution, and infections can modulate the microbiota system to regulate intrinsic neuronal activity and brain reserves through the vagus nerve and enteric nervous system. Microbiota-derived molecules can trigger continuous activation of the microglial sensome, groups of receptors and proteins that permit microglia to remodel the brain neurochemistry based on complex environmental activities. This remodeling causes aberrant brain plasticity as early as fetal developmental stages, and after the onset of first-episode psychosis. In the central nervous system, microglia, the resident immune surveillance cells, are involved in neurogenesis, phagocytosis of synapses and neurological dysfunction. Here, we review recent emerging experimental and clinical evidence regarding the gut-brain microglia axis involvement in SCZ pathology and etiology, the hypothesis of brain reserve and accelerated aging induced by dietary habits, stress, pollution, infections, and other factors. We also include in our review the possibilities and consequences of gut dysbiosis activities on microglial function and dysfunction, together with the effects of antipsychotics on the gut microbiome: therapeutic and adverse effects, role of fecal microbiota transplant and psychobiotics on microglial sensomes, brain reserves and SCZ-derived accelerated aging. We end the review with suggestions that may be applicable to the clinical setting. For example, we propose that psychobiotics might contribute to antipsychotic-induced therapeutic benefits or adverse effects, as well as reduce the aging process through the gut-brain microglia axis. Overall, we hope that this review will help increase the understanding of SCZ pathogenesis as related to chronobiology and the gut microbiome, as well as reveal new concepts that will serve as novel treatment targets for SCZ.}, }
@article {pmid37255721, year = {2023}, author = {Solanki, R and Karande, A and Ranganathan, P}, title = {Emerging role of gut microbiota dysbiosis in neuroinflammation and neurodegeneration.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1149618}, pmid = {37255721}, issn = {1664-2295}, abstract = {Alzheimer's disease (AD), is a chronic age-related progressive neurodegenerative disorder, characterized by neuroinflammation and extracellular aggregation of Aβ peptide. Alzheimer's affects every 1 in 14 individuals aged 65 years and above. Recent studies suggest that the intestinal microbiota plays a crucial role in modulating neuro-inflammation which in turn influences Aβ deposition. The gut and the brain interact with each other through the nervous system and chemical means via the blood-brain barrier, which is termed the Microbiota Gut Brain Axis (MGBA). It is suggested that the gut microbiota can impact the host's health, and numerous factors, such as nutrition, pharmacological interventions, lifestyle, and geographic location, can alter the gut microbiota composition. Although, the exact relationship between gut dysbiosis and AD is still elusive, several mechanisms have been proposed as drivers of gut dysbiosis and their implications in AD pathology, which include, action of bacteria that produce bacterial amyloids and lipopolysaccharides causing macrophage dysfunction leading to increased gut permeability, hyperimmune activation of inflammatory cytokines (IL-1β, IL-6, IL-8, and NLRP3), impairment of gut- blood brain barrier causing deposition of Aβ in the brain, etc. The study of micro-organisms associated with dysbiosis in AD with the aid of appropriate model organisms has recognized the phyla Bacteroidetes and Firmicutes which contain organisms of the genus Escherichia, Lactobacillus, Clostridium, etc., to contribute significantly to AD pathology. Modulating the gut microbiota by various means, such as the use of prebiotics, probiotics, antibiotics or fecal matter transplantation, is thought to be a potential therapeutic intervention for the treatment of AD. This review aims to summarize our current knowledge on possible mechanisms of gut microbiota dysbiosis, the role of gut brain microbiota axis in neuroinflammation, and the application of novel targeted therapeutic approaches that modulate the gut microbiota in treatment of AD.}, }
@article {pmid37253485, year = {2023}, author = {Chen, L and Guo, L and Feng, S and Wang, C and Cui, Z and Wang, S and Lu, Q and Chang, H and Hang, B and Snijders, AM and Mao, JH and Lu, Y and Ding, D}, title = {Fecal microbiota transplantation ameliorates type 2 diabetes via metabolic remodeling of the gut microbiota in db/db mice.}, journal = {BMJ open diabetes research &amp; care}, volume = {11}, number = {3}, pages = {}, pmid = {37253485}, issn = {2052-4897}, support = {R01 ES031322/ES/NIEHS NIH HHS/United States ; }, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 2/therapy ; Feces ; Inflammation/pathology ; }, abstract = {INTRODUCTION: Gut microbiome (GM) deregulation has been implicated in major conditions such as obesity and type 2 diabetes (T2DM). Our previous prospective study indicated that fecal microbiota transplantation (FMT) successfully improved patients with T2DM. We hypothesized that FMT may be a potential therapeutic method for T2DM, but its precise mechanisms in T2DM remains to be elucidated.<br><br>RESEARCH DESIGN AND METHODS: Eight db/m mice were FMT donors and control mice, and 16 genetically diabetic db/db mice were equally divided into two groups (db/db+phosphate-buffered saline (PBS) group, db/db+FMT group). The db/db+FMT group was administered fresh fecal suspension (0.2 mL/mice) daily for 4&#x2009;weeks. Analysis of the GM and serum metabolome was carried out by 16S ribosomal RNA sequencing and liquid chromatogram-mass spectrometry, respectively. Effects of FMT on the gut barrier and pancreas were assessed using protein assays, messenger RNA, immunohistology and clinical indicators testing.<br><br>RESULTS: Our results showed that FMT treatment of db/db mice relieves a series of clinical indicators, including fasting plasma glucose, serum insulin and oral glucose tolerance test among others. Compared with non-diabetic control mice, db/db+PBS mice exhibited decreased abundance of Ruminococaceae, Porphyromonadaceae and increased abundance of Rikenellaceae and Lactobacillaceae. FMT treatment reversed this effect on the microbiome. Eleven metabolites were changed between the db/db+PBS&#x2009;and db/db+FMT groups. Correlation analysis showed that the structural changes of the GM were correlated with host metabolite levels. We further showed that FMT treatment of db/db mice improved intestinal barrier function, reduced inflammation and caused an alteration in the number of circulating immune cells.<br><br>CONCLUSIONS: FMT-mediated changes in the GM, serum metabolites, intestinal epithelial barrier, inflammation and circulating immune cells play an important role in the efficacy of FMT on T2DM disease progression.}, }
@article {pmid37252544, year = {2023}, author = {Malik, H and Malik, H and Uderani, M and Berhanu, M and Soto, CJ and Saleem, F}, title = {Fulminant Hepatitis A and E Co-infection Leading to Acute Liver Failure: A Case Report.}, journal = {Cureus}, volume = {15}, number = {4}, pages = {e38101}, pmid = {37252544}, issn = {2168-8184}, abstract = {Acute liver failure (ALF) is a severe clinical condition with a high mortality rate. Although several factors can cause ALF, viral hepatitis remains one of the leading causes. Hepatitis A virus (HAV) and hepatitis E virus (HEV), which typically cause self-limiting acute disease, are rare but emerging causes of ALF, especially when both viruses infect the same individual. Both of these hepatotropic viruses share an enteric route and are most commonly transmitted through the fecal-oral route. The impact of HAV/HEV co-infection on acute hepatitis prognosis is not entirely understood, but dual infection can further exacerbate liver damage, leading to fulminant hepatic failure (FHF) with a higher mortality rate than a single virus infection. Here, we present a case of a 32-year-old male with no prior liver disease who presented to the emergency department with a two-week history of jaundice, abdominal pain, and hepatomegaly. Upon admission, he was disoriented with grade 2 encephalopathy. After a thorough investigation, co-infection with hepatitis A and E was identified as the primary cause of his ALF. The patient underwent intensive medical treatment and interventions, including dialysis. Unfortunately, the patient's survival was not possible due to the absence of availability of a transplanted organ, which is currently the only definitive treatment option. This case report underscores the significance of prompt diagnosis, timely intervention, and the accessibility of transplantation in the survival of liver failure, as it remains the sole definitive treatment for acute liver failure. Moreover, it provides a concise overview of the current literature on fulminant co-infection of HAV and HEV, including epidemiology, clinical characteristics, pathogenesis, diagnosis, treatment, and risk factors associated with co-infection of hepatitis A and E and their role in causing ALF. It also highlights the significance of identifying high-risk populations and implementing appropriate prevention and control measures such as vaccination, practising good hygiene and sanitation, and avoiding the consumption of contaminated food and water.}, }
@article {pmid37249910, year = {2023}, author = {Margolis, EB and Alfaro, GM and Sun, Y and Dallas, RH and Allison, KJ and Ferrolino, J and Ross, HS and Davis, AE and Jia, Q and Turner, P and Mackay, V and Morin, CE and Triplett, BM and Klein, EJ and Englund, JA and Tang, L and Hayden, RT}, title = {Microbiota Predict Infections and Acute Graft-Versus-Host Disease After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.}, journal = {The Journal of infectious diseases}, volume = {228}, number = {5}, pages = {627-636}, pmid = {37249910}, issn = {1537-6613}, mesh = {Adult ; Humans ; Child ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Bacteria/genetics ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Graft vs Host Disease ; }, abstract = {BACKGROUND: Despite preventive measures, infections continue to pose significant risks to pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The gut microbiota has been linked to clinical outcomes following adult allo-HCT. This study evaluated whether similar disruptions or differing microbiota patterns were associated with infection risk in pediatric allo-HCT.<br><br>METHODS: In a prospective observational study, fecal samples were obtained from 74 children before conditioning and upon neutrophil recovery. Microbiome signatures identified through sequencing were examined for their associations with infections or acute graft-versus-host disease (aGVHD) in the first-year post-HCT using Cox proportional hazards analysis.<br><br>RESULTS: Microbiome disruption in adults, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (eg, Lachnoclostridium, Parabacteroides) prior to conditioning predicted bacteremia risk (Cox hazard ratio [HR], 3.89). A distinct ratio of oral (eg, Rothia, Veillonella) to intestinal anaerobes (eg, Anaerobutyricum, Romboutsia) at neutrophil recovery predicted likelihood of bacterial infections (Cox HR, 1.81) and viral enterocolitis (Cox HR, 1.96).<br><br>CONCLUSIONS: Interactions between medical interventions, pediatric hosts, and microbial communities contribute to microbiota signatures that predict infections. Further multicenter study is necessary to validate the generalizability of these ratios as biomarkers.}, }
@article {pmid37249187, year = {2023}, author = {Horesh, N and Emile, SH and Khan, SM and Freund, MR and Garoufalia, Z and Silva-Alvarenga, E and Gefen, R and Wexner, SD}, title = {Meta-analysis of Randomized Clinical Trials on Long-term Outcomes of Surgical Treatment of Perforated Diverticulitis.}, journal = {Annals of surgery}, volume = {278}, number = {5}, pages = {e966-e972}, doi = {10.1097/SLA.0000000000005909}, pmid = {37249187}, issn = {1528-1140}, mesh = {Humans ; Anastomosis, Surgical/adverse effects ; Colostomy ; *Diverticulitis/surgery ; *Diverticulitis, Colonic/complications/surgery ; *Intestinal Perforation/surgery/complications ; *Laparoscopy/methods ; *Peritonitis/etiology/surgery ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {OBJECTIVE: To assess long-term outcomes of patients with perforated diverticulitis treated with resection or laparoscopic lavage (LL).<br><br>BACKGROUND: Surgical treatment of perforated diverticulitis has changed in the last few decades. LL and increasing evidence that primary anastomosis (PRA) is feasible in certain patients have broadened surgical options. However, debate about the optimal surgical strategy lingers.<br><br>METHODS: PubMed, Scopus, and Web of Science were searched for randomized clinical trials (RCT) on surgical treatment of perforated diverticulitis from inception to October 2022. Long-term reports of RCT comparing surgical interventions for the treatment of perforated diverticulitis were selected. The main outcome measures were long-term ostomy, long-term complications, recurrence, and reintervention rates.<br><br>RESULTS: After screening 2431 studies, 5 long-term follow-up studies of RCT comprising 499 patients were included. Three studies, excluding patients with fecal peritonitis, compared LL and colonic resection, and 2 compared PRA and Hartmann procedures. LL had lower odds of long-term ostomy [odds ratio (OR) = 0.133, 95% CI: 0.278-0.579; P < 0.001] and reoperation (OR = 0.585, 95% CI: 0.365-0.937; P = 0.02) compared with colonic resection but higher odds of diverticular disease recurrence (OR = 5.8, 95% CI: 2.33-14.42; P < 0.001). Colonic resection with PRA had lower odds of long-term ostomy (OR = 0.02, 95% CI: 0.003-0.195; P < 0.001), long-term complications (OR = 0.195, 95% CI: 0.113-0.335; P < 0.001), reoperation (OR = 0.2, 95% CI: 0.108-0.384; P < 0.001), and incisional hernia (OR = 0.184, 95% CI: 0.102-0.333; P < 0.001). There was no significant difference in odds of mortality among the procedures.<br><br>CONCLUSIONS: Long-term follow-up of patients who underwent emergency surgery for perforated diverticulitis showed that LL had lower odds of long-term ostomy and reoperation, but more risk for disease recurrence when compared with resection in purulent peritonitis. Colonic resection with PRA had better long-term outcomes than the Hartmann procedure for fecal peritonitis.}, }
@article {pmid37247177, year = {2023}, author = {Mohan, BP and Loganathan, P and Khan, SR and Garg, G and Muthusamy, A and Ponnada, S and Pasam, RT and Chandan, S and Tuteja, A}, title = {Fecal microbiota transplant delivered via invasive routes in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {42}, number = {3}, pages = {315-323}, pmid = {37247177}, issn = {0975-0711}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Irritable Bowel Syndrome/therapy/diagnosis ; Quality of Life ; *Gastrointestinal Microbiome ; Randomized Controlled Trials as Topic ; Feces ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) results in significant loss of quality of life. Management guidelines do not recommend fecal microbiota transplant (FMT) for IBS based on weak evidence as refined data is lacking. We performed a systematic review and meta-analysis to ascertain the pooled clinical outcomes of FMT in IBS, delivered via invasive routes.<br><br>METHODS: Multiple databases were searched through January 2023 to identify studies that reported on FMT treatment in IBS by invasive routes. Standard meta-analysis methodology using the random-effects model was used. Heterogeneity was assessed by I[2]% and 95% predication interval.<br><br>RESULTS: Five studies were included. As many as 377&#xa0;IBS patients were assessed, of which 238 received FMT and 139 received placebo. One study used nasojejunal tubes, one esophagogastroduodenoscopy&#xa0;and three colonoscopy for FMT delivery. FMT via colonoscopy was performed as a one-time procedure instilled into the cecum. Two studies used 30 g of stool from a single universal donor and one study used 50-80 g of pooled donor feces. The pooled odds ratio of improvement in IBS symptoms with FMT was significantly better as compared to that of placebo OR = 2.9 (95% CI [1.6-5.2, I[2] = 62%, p < 0.001]). This was true for studies that exclusively used colonoscopy (OR = 2.1 [1.1-4.2, p = 0.04]). In the FMT arm, 10 patients (10.6%) reported abdomen pain and worsening of symptoms with bloating and six patients (6.3%) reported diarrhea.<br><br>CONCLUSION: FMT delivered via invasive routes, especially colonoscopy, demonstrated significant improvement in IBS symptoms. A single FMT consisting of 30 g or more of single universal donor feces instilled into the cecum is the predominant modality.}, }
@article {pmid37247104, year = {2023}, author = {Ganji, N and Li, B and Lee, C and Pierro, A}, title = {Necrotizing enterocolitis: recent advances in treatment with translational potential.}, journal = {Pediatric surgery international}, volume = {39}, number = {1}, pages = {205}, pmid = {37247104}, issn = {1437-9813}, support = {353857/CAPMC/CIHR/Canada ; }, mesh = {Female ; Infant, Newborn ; Humans ; *Enterocolitis, Necrotizing/therapy ; *Infant, Newborn, Diseases ; Milk, Human ; }, abstract = {Necrotizing enterocolitis (NEC) is one of the most prevalent and devastating gastrointestinal disorders in neonates. Despite advances in neonatal care, the incidence and mortality due to NEC remain high, highlighting the need to devise novel treatments for this disease. There have been a number of recent advancements in therapeutic approaches for the treatment of NEC; these involve remote ischemic conditioning (RIC), stem cell therapy, breast milk components (human milk oligosaccharides, exosomes, lactoferrin), fecal microbiota transplantation, and immunotherapy. This review summarizes the most recent advances in NEC treatment currently underway as well as their applicability and associated challenges and limitations, with the aim to provide new insight into the paradigm of care for NEC worldwide.}, }
@article {pmid37246923, year = {2023}, author = {El-Salhy, M}, title = {Intestinal bacteria associated with irritable bowel syndrome and chronic fatigue.}, journal = {Neurogastroenterology and motility}, volume = {35}, number = {9}, pages = {e14621}, doi = {10.1111/nmo.14621}, pmid = {37246923}, issn = {1365-2982}, mesh = {Butyrates ; Epithelial Cells ; *Fatigue Syndrome, Chronic/therapy ; Firmicutes ; Humans ; *Irritable Bowel Syndrome/therapy ; }, abstract = {The etiology of irritable bowel syndrome (IBS) is unknown. Abnormal intestinal bacterial profiles and low bacterial diversity appear to play important roles in the pathophysiology of IBS. This narrative review was designed to present recent observations made relating to fecal microbiota transplantation (FMT), which implicate possible roles of 11 intestinal bacteria in the pathophysiology of IBS. The intestinal abundances of nine of these bacteria increased after FMT in patients with IBS, and these increases were inversely correlated with IBS symptoms and fatigue severity. These bacteria were Alistipes spp., Faecalibacterium prausnitzii, Eubacterium biforme, Holdemanella biformis, Prevotella spp., Bacteroides stercoris, Parabacteroides johnsonii, Bacteroides zoogleoformans, and Lactobacillus spp. The intestinal abundances of two bacteria were decreased in patients with IBS after FMT and were correlated with the severity of IBS symptoms and fatigue (Streptococcus thermophilus and Coprobacillus cateniformis). Ten of these bacteria are anaerobic and one (Streptococcus thermophilus) is facultative anaerobic. Several of these bacteria produce short-chain fatty acids, especially butyrate, which is used as an energy source by large intestine epithelial cells. Moreover, it modulates the immune response and hypersensitivity of the large intestine and decreases intestinal cell permeability and intestinal motility. These bacteria could be used as probiotics to improve these conditions. Protein-rich diets could increase the intestinal abundance of Alistipes, and plant-rich diet could increase the intestinal abundance of Prevotella spp., and consequently improve IBS and fatigue.}, }
@article {pmid37246133, year = {2023}, author = {Wu, R and Xiong, R and Li, Y and Chen, J and Yan, R}, title = {Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation.}, journal = {Journal of autoimmunity}, volume = {141}, number = {}, pages = {103062}, doi = {10.1016/j.jaut.2023.103062}, pmid = {37246133}, issn = {1095-9157}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy ; *Colitis, Ulcerative ; Metabolome ; Dysbiosis ; Feces ; }, abstract = {Gut dysbiosis has been associated with inflammatory bowel disease (IBD), one of the most common gastrointestinal diseases. The microbial communities play essential roles in host physiology, with profound effects on immune homeostasis, directly or via their metabolites and/or components. There are increasing clinical trials applying fecal microbiota transplantation (FMT) with Crohn's disease (CD) and ulcerative colitis (UC). The restoration of dysbiotic gut microbiome is considered as one of the mechanisms of FMT therapy. In this work, latest advances in the alterations in gut microbiome and metabolome features in IBD patients and experimental mechanistic understanding on their contribution to the immune dysfunction were reviewed. Then, the therapeutic outcomes of FMT on IBD were summarized based on clinical remission, endoscopic remission and histological remission of 27 clinical trials retrieved from PubMed which have been registered on ClinicalTrials.gov with the results been published in the past 10 years. Although FMT is established as an effective therapy for both subtypes of IBD, the promising outcomes are not always achieved. Among the 27 studies, only 11 studies performed gut microbiome profiling, 5 reported immune response alterations and 3 carried out metabolome analysis. Generally, FMT partially restored typical changes in IBD, resulted in increased α-diversity and species richness in responders and similar but less pronounced shifts of patient microbial and metabolomics profiles toward donor profiles. Measurements of immune responses to FMT mainly focused on T cells and revealed divergent effects on pro-/anti-inflammatory functions. The very limited information and the extremely confounding factors in the designs of the FMT trials significantly hindered a reasonable conclusion on the mechanistic involvement of gut microbiota and metabolites in clinical outcomes and an analysis of the inconsistencies.}, }
@article {pmid37245237, year = {2023}, author = {Li, DS and Wu, YR and Du, WH and Zhu, YL and Zhang, WJ and Fu, Y and Yang, GB}, title = {The composition of the intestinal microbiota after allogeneic haematopoietic stem cell transplantation and its association with graft versus host disease as assessed by 16Sribosomal ribonucleic acid.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {74}, number = {1}, pages = {}, doi = {10.26402/jpp.2023.1.10}, pmid = {37245237}, issn = {1899-1505}, mesh = {Humans ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Graft vs Host Disease/etiology ; Risk Factors ; }, abstract = {To observe the evolution of the intestinal microbiota in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and discuss the relationship between the intestinal microbiota and graft-versus-host disease (GVHD). In this study, 11 patients who underwent allo-HSCT in the Aerospace Central Hospital from January 2021 to October 2021 were selected, along with 11 donors. Fecal specimens were collected 7 times: at admission, after pre-treatment, and every 3 weeks after transplantation from patients and once from donors. The composition of the intestinal microbiota and its association with GVHD after allogeneic hematopoietic stem cell transplantation were analyzed by 16S rRNA sequencing. Of the 11 patients, 5 developed GVHD, and 6 did not. The diversity of the intestinal microbiota among GVHD patients first increased and then decreased after transplantation, while that among non-GVHD patients first increased and then tended to be stable. The diversity of the intestinal microbiota among GVHD patients was lower than that among non-GVHD patients before pre-treatment and after transplantation. The taxa diversity of the intestinal microbiota in the non-GVHD group was better than that in the GVHD group before allo-HSCT, and the difference was statistically significant (P<0.05 for OTUs and CHAO1 index). The taxa abundance of Enterococcaceae 2.16% (2.13%, 2.22%) before allo-HSCT was significantly higher than that in the non-GVHD group 1.33% (0.27%, 1.52%), and the difference was statistically significant (P=0.004). There was no significant difference between the GVHD group and the non-GVHD group in the diversity of the intestinal microbiota of donors (P<0.05). The characteristics of the intestinal microbiota in the final sample of patients in the GVHD group were similar to the preoperative structure of the intestinal microbiota. In conclusion: The decrease in the diversity of the intestinal microbiota after HSCT may be a risk factor for the occurrence of GVHD. The presence of Enterococcaceae in the intestinal microbiota may be associated with an increased risk of developing GVHD. The intestinal microbiota reconstitute to be close to the intestinal microbiota composition of the donors in the non-GVHD group.}, }
@article {pmid37245211, year = {2023}, author = {Alves, JC and Santos, A and Jorge, P and Pitães, &#xc2;}, title = {Faecal microbiome transplantation improves clinical signs of chronic idiopathic large bowel diarrhoea in working dogs.}, journal = {The Veterinary record}, volume = {193}, number = {10}, pages = {e3052}, doi = {10.1002/vetr.3052}, pmid = {37245211}, issn = {2042-7670}, mesh = {Animals ; Dogs ; Fecal Microbiota Transplantation/veterinary ; *Psyllium/therapeutic use ; Working Dogs ; Diarrhea/therapy/veterinary ; Feces/microbiology ; *Inflammatory Bowel Diseases/therapy/veterinary ; *Dog Diseases/diagnosis ; }, abstract = {BACKGROUND: Chronic diarrhoea is a common clinical sign in dogs with chronic enteropathy, and psyllium husk has been shown to improve clinical signs in affected dogs. The aim of this study was to investigate whether faecal microbiome transplant has a similar effect in alleviating clinical signs in dogs with chronic large bowel diarrhoea.<br><br>METHOD: Thirty large-breed working dogs with chronic large bowel diarrhoea were divided into a psyllium group (PG) and a faecal microbiome transplant group (FMTG). To the PG, 16&#xa0;g/day of psyllium husk was administered for 30 days. The FMTG received faecal microbiome transplantation (FMT) once via enema. A daily log of faecal characteristics was kept, and the dogs' canine inflammatory bowel disease index (CIBDAI) and body condition scores (BCS) were determined. A Wilcoxon-Mann-Whitney test was used to compare group results. In addition, the Kaplan-Meier test was used to evaluate the occurrence rate of 1 day or more of diarrhoea and 2 days or more of diarrhoea by day 30.<br><br>RESULTS: The sample had a mean age of 3.9&#xa0;&#xb1;&#xa0;2.1 years and a bodyweight of 25.3&#xa0;&#xb1;&#xa0;6.8&#xa0;kg. The FMTG showed a more rapid onset of CIBDAI improvement but no difference in other measures. At 30 days, the FMTG showed a greater improvement in bodyweight and BCS, but no differences were observed in faecal scores, defaecation frequency and time of appearance of episodes of diarrhoea. Time played a significant positive role in the results observed across both groups (p < 0.05).<br><br>LIMITATIONS: This study did not compare the microbiomes of the dogs before and after treatment, so the role of specific types of bacteria cannot be determined.<br><br>CONCLUSION: Psyllium husk and FMT had similar effects in improving clinical signs of chronic large bowel diarrhoea.}, }
@article {pmid37244385, year = {2023}, author = {Wang, L and Zhang, K and Zeng, Y and Luo, Y and Peng, J and Zhang, J and Kuang, T and Fan, G}, title = {Gut mycobiome and metabolic diseases: The known, the unknown, and the future.}, journal = {Pharmacological research}, volume = {193}, number = {}, pages = {106807}, doi = {10.1016/j.phrs.2023.106807}, pmid = {37244385}, issn = {1096-1186}, mesh = {Humans ; *Mycobiome ; Saccharomyces cerevisiae ; *Gastrointestinal Microbiome ; *Non-alcoholic Fatty Liver Disease/therapy ; *Diabetes Mellitus, Type 2 ; Obesity ; Bacteria ; }, abstract = {Metabolic diseases, such as type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD) and obesity, have become a major public health problem worldwide. In recent years, most research on the role of gut microbes in metabolic diseases has focused on bacteria, whereas fungal microbes have been neglected. This review aims to provide a comprehensive overview of gut fungal alterations in T2DM, obesity, and NAFLD, and to discuss the mechanisms associated with disease development. In addition, several novel strategies targeting gut mycobiome and/or their metabolites to improve T2DM, obesity and NAFLD, including fungal probiotics, antifungal drugs, dietary intervention, and fecal microbiota transplantation, are critically discussed. The accumulated evidence suggests that gut mycobiome plays an important role in the occurrence and development of metabolic diseases. The possible mechanisms by which the gut mycobiome affects metabolic diseases include fungal-induced immune responses, fungal-bacterial interactions, and fungal-derived metabolites. Candida albicans, Aspergillus and Meyerozyma may be potential pathogens of metabolic diseases because they can activate the immune system and/or produce harmful metabolites. Moreover, Saccharomyces boulardii, S. cerevisiae, Alternaria, and Cochliobolus fungi may have the potential to improve metabolic diseases. The information may provide an important reference for the development of new therapeutics for metabolic diseases based on gut mycobiome.}, }
@article {pmid37243505, year = {2023}, author = {Bruggeling, CE and Te Groen, M and Garza, DR and van Heeckeren Tot Overlaer, F and Krekels, JPM and Sulaiman, BC and Karel, D and Rulof, A and Schaaphok, AR and Hornikx, DLAH and Nagtegaal, ID and Dutilh, BE and Hoentjen, F and Boleij, A}, title = {Bacterial Oncotraits Rather than Spatial Organization Are Associated with Dysplasia in Ulcerative Colitis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {17}, number = {11}, pages = {1870-1881}, pmid = {37243505}, issn = {1876-4479}, support = {//Scientific Research 'Veni/ ; //Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Colitis, Ulcerative/pathology ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Hyperplasia ; Biomarkers ; }, abstract = {BACKGROUND AND AIMS: Colonic bacterial biofilms are frequently present in ulcerative colitis [UC] and may increase dysplasia risk through pathogens expressing oncotraits. This prospective cohort study aimed to determine [1] the association of oncotraits and longitudinal biofilm presence with dysplasia risk in UC, and [2] the relation of bacterial composition with biofilms and dysplasia risk.<br><br>METHODS: Faeces and left- and right-sided colonic biopsies were collected from 80 UC patients and 35 controls. Oncotraits [FadA of Fusobacterium, BFT of Bacteroides fragilis, colibactin [ClbB] and Intimin [Eae] of Escherichia coli] were assessed in faecal DNA with multiplex quantitative polymerase chain reaction [qPCR]. Biopsies were screened for biofilms [n&#x2005;=&#x2005;873] with 16S rRNA fluorescent in situ hybridiation. Shotgun metagenomic sequencing [n&#x2005;=&#x2005;265], and ki67-immunohistochemistry were performed. Associations were determined with a mixed-effects regression model.<br><br>RESULTS: Biofilms were highly prevalent in UC patients [90.8%] with a median persistence of 3 years (interquartile range [IQR] 2-5 years). Biofilm-positive biopsies showed increased epithelial hypertrophy [p&#x2005;=&#x2005;0.025] and a reduced Shannon diversity independent of disease status [p&#x2005;=&#x2005;0.015], but were not significantly associated with dysplasia in UC: adjusted odds ratio [aOR] 1.45, 95% confidence interval [CI] 0.63-3.40. In contrast, ClbB independently associated with dysplasia [aOR 7.16, 95% CI 1.75-29.28], and FadA and Fusobacteriales were associated with a decreased dysplasia risk in UC [aOR 0.23, 95% CI 0.06-0.83, p&#x2005;<0.01].<br><br>CONCLUSIONS: Biofilms are a hallmark of UC; however, because of their high prevalence are a poor biomarker for dysplasia. In contrast, colibactin presence and FadA absence independently associate with dysplasia in UC and might therefore be valuable biomarkers for future risk stratification and intervention strategies.}, }
@article {pmid37243442, year = {2023}, author = {Marasco, G and Buttitta, F and Cremon, C and Barbaro, MR and Stanghellini, V and Barbara, G}, title = {The role of microbiota and its modulation in colonic diverticular disease.}, journal = {Neurogastroenterology and motility}, volume = {35}, number = {12}, pages = {e14615}, doi = {10.1111/nmo.14615}, pmid = {37243442}, issn = {1365-2982}, support = {//Fondazione Carisbo/ ; //Fondazione del Monte di Bologna e Ravenna/ ; //Horizon 2020 Framework Programme/ ; //Italian Ministry of Health/ ; }, mesh = {Humans ; *Probiotics ; *Diverticulosis, Colonic ; *Diverticular Diseases ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Diverticular disease (DD) is a common condition in Western countries. The role of microbiota in the pathogenesis of DD and its related symptoms has been frequently postulated since most complications of this disease are bacteria-driven and most therapies rely on microbiota modulation. Preliminary data showed fecal microbial imbalance in patients with DD, particularly when symptomatic, with an increase of pro-inflammatory and potentially pathogenetic bacteria. In addition, bacterial metabolic markers can mirror specific pathways of the disease and may be even used for monitoring treatment effects. All treatments currently suggested for DD can affect microbiota structure and metabolome compositions.<br><br>PURPOSE: Sparse evidence is available linking gut microbiota perturbations, diverticular disease pathophysiology, and symptom development. We aimed to summarize the available knowledge on gut microbiota evaluation in diverticular disease, with a focus on symptomatic uncomplicated DD, and the relative treatment strategies.}, }
@article {pmid37241738, year = {2023}, author = {Huang, Y and Ying, N and Zhao, Q and Chen, J and Teow, SY and Dong, W and Lin, M and Jiang, L and Zheng, H}, title = {Amelioration of Obesity-Related Disorders in High-Fat Diet-Fed Mice following Fecal Microbiota Transplantation from Inulin-Dosed Mice.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {10}, pages = {}, pmid = {37241738}, issn = {1420-3049}, support = {2022KY1215//Medical and Health Science and Technology Project of Zhejiang Province/ ; }, mesh = {Animals ; Mice ; *Inulin/pharmacology ; *Diet, High-Fat/adverse effects ; Fecal Microbiota Transplantation ; Mice, Obese ; Obesity/metabolism ; Mice, Inbred C57BL ; }, abstract = {The role of inulin in alleviating obesity-related disorders has been documented; yet, its underlying mechanisms still need to be further investigated. This study attempted to elucidate the causative link between the gut microbiota and the beneficial effect of inulin on obesity-related disorders via transferring the fecal microbiota from inulin-dosed mice to high-fat diet (HFD)-induced obese recipient mice. The results show that inulin supplementation can decrease body weight, fat accumulation, and systemic inflammation and can also enhance glucose metabolism in HFD-induced obese mice. Treatment with inulin reshaped the structure and composition of the gut microbiota in HFD-induced obese mice, as characterized by increases in the relative abundances of Bifidobacterium and Muribaculum and decreases in unidentified_Lachnospiraceae and Lachnoclostridium. In addition, we found that these favorable effects of inulin could be partially transferable by fecal microbiota transplantation, and Bifidobacterium and Muribaculum might be the key bacterial genera. Therefore, our results suggest that inulin ameliorates obesity-related disorders by targeting the gut microbiota.}, }
@article {pmid37240769, year = {2023}, author = {Keathley, J and White, J and Reid, G}, title = {The Impact of Nutrition, Physical Activity, Beneficial Microbes, and Fecal Microbiota Transplant for Improving Health.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {5}, pages = {}, pmid = {37240769}, issn = {2075-1729}, support = {NA//Natural Science and Engineering Research Council of Canada/ ; }, abstract = {The recognition that microbes are integral to human life has led to studies on how to manipulate them in favor of health outcomes. To date, there has been no conjoint recommendation for the intake of dietary compounds that can complement the ingested organisms in terms of promoting an improved health outcome. The aim of this review is to discuss how beneficial microbes in the form of probiotics, fermented foods, and donor feces are being used to manage health. In addition, we explore the rationale for selecting beneficial microbial strains and aligning diets to accommodate their propagation in the gut. A pilot clinical trial design is presented to examine the effects of probiotics and exercise in patients with phenylketonuria (PKU); it is the most common inborn error of amino acid metabolism, and it is a complication that requires lifelong dietary intervention. The example design is provided to illustrate the importance of using omics technology to see if the intervention elevates neuroactive biogenic amines in the plasma; increases the abundance of Eubacterium rectale, Coprococcus eutactus, Akkermansia muciniphila, or Butyricicoccus; and increases Escherichia/Shigella in the gut, all as markers of improved health. By emphasizing the combined importance of diet, microbial supplements, and the gut microbiome, we hope that future studies will better align these components, not only to improve outcomes, but also to enhance our understanding of the mechanisms.}, }
@article {pmid37238943, year = {2023}, author = {Shahbazi, A and Sepehrinezhad, A and Vahdani, E and Jamali, R and Ghasempour, M and Massoudian, S and Sahab Negah, S and Larsen, FS}, title = {Gut Dysbiosis and Blood-Brain Barrier Alteration in Hepatic Encephalopathy: From Gut to Brain.}, journal = {Biomedicines}, volume = {11}, number = {5}, pages = {}, pmid = {37238943}, issn = {2227-9059}, abstract = {A common neuropsychiatric complication of advanced liver disease, hepatic encephalopathy (HE), impacts the quality of life and length of hospital stays. There is new evidence that gut microbiota plays a significant role in brain development and cerebral homeostasis. Microbiota metabolites are providing a new avenue of therapeutic options for several neurological-related disorders. For instance, the gut microbiota composition and blood-brain barrier (BBB) integrity are altered in HE in a variety of clinical and experimental studies. Furthermore, probiotics, prebiotics, antibiotics, and fecal microbiota transplantation have been shown to positively affect BBB integrity in disease models that are potentially extendable to HE by targeting gut microbiota. However, the mechanisms that underlie microbiota dysbiosis and its effects on the BBB are still unclear in HE. To this end, the aim of this review was to summarize the clinical and experimental evidence of gut dysbiosis and BBB disruption in HE and a possible mechanism.}, }
@article {pmid37237771, year = {2023}, author = {Airola, C and Severino, A and Porcari, S and Fusco, W and Mullish, BH and Gasbarrini, A and Cammarota, G and Ponziani, FR and Ianiro, G}, title = {Future Modulation of Gut Microbiota: From Eubiotics to FMT, Engineered Bacteria, and Phage Therapy.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {37237771}, issn = {2079-6382}, abstract = {The human gut is inhabited by a multitude of bacteria, yeasts, and viruses. A dynamic balance among these microorganisms is associated with the well-being of the human being, and a large body of evidence supports a role of dysbiosis in the pathogenesis of several diseases. Given the importance of the gut microbiota in the preservation of human health, probiotics, prebiotics, synbiotics, and postbiotics have been classically used as strategies to modulate the gut microbiota and achieve beneficial effects for the host. Nonetheless, several molecules not typically included in these categories have demonstrated a role in restoring the equilibrium among the components of the gut microbiota. Among these, rifaximin, as well as other antimicrobial drugs, such as triclosan, or natural compounds (including evodiamine and polyphenols) have common pleiotropic characteristics. On one hand, they suppress the growth of dangerous bacteria while promoting beneficial bacteria in the gut microbiota. On the other hand, they contribute to the regulation of the immune response in the case of dysbiosis by directly influencing the immune system and epithelial cells or by inducing the gut bacteria to produce immune-modulatory compounds, such as short-chain fatty acids. Fecal microbiota transplantation (FMT) has also been investigated as a procedure to restore the equilibrium of the gut microbiota and has shown benefits in many diseases, including inflammatory bowel disease, chronic liver disorders, and extraintestinal autoimmune conditions. One of the most significant limits of the current techniques used to modulate the gut microbiota is the lack of tools that can precisely modulate specific members of complex microbial communities. Novel approaches, including the use of engineered probiotic bacteria or bacteriophage-based therapy, have recently appeared as promising strategies to provide targeted and tailored therapeutic modulation of the gut microbiota, but their role in clinical practice has yet to be clarified. The aim of this review is to discuss the most recently introduced innovations in the field of therapeutic microbiome modulation.}, }
@article {pmid37237476, year = {2023}, author = {Pezzino, S and Sofia, M and Mazzone, C and Castorina, S and Puleo, S and Barchitta, M and Agodi, A and Gallo, L and La Greca, G and Latteri, S}, title = {Gut Microbiome in the Progression of NAFLD, NASH and Cirrhosis, and Its Connection with Biotics: A Bibliometric Study Using Dimensions Scientific Research Database.}, journal = {Biology}, volume = {12}, number = {5}, pages = {}, pmid = {37237476}, issn = {2079-7737}, abstract = {There is growing evidence that gut microbiota dysbiosis is linked to the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), from the initial stage of disease until the progressive stage of nonalcoholic steatohepatitis (NASH) and the final stage of cirrhosis. Conversely, probiotics, prebiotics, and synbiotics have shown promise in restoring dysbiosis and lowering clinical indicators of disease in a number of both preclinical and clinical studies. Additionally, postbiotics and parabiotics have recently garnered some attention. The purpose of this bibliometric analysis is to assess recent publishing trends concerning the role of the gut microbiome in the progression of NAFLD, NASH and cirrhosis and its connection with biotics. The free access version of the Dimensions scientific research database was used to find publications in this field from 2002 to 2022. VOSviewer and Dimensions' integrated tools were used to analyze current research trends. Research into the following topics is expected to emerge in this field: (1) evaluation of risk factors which are correlated with the progression of NAFLD, such as obesity and metabolic syndrome; (2) pathogenic mechanisms, such as liver inflammation through toll-like receptors activation, or alteration of short-chain fatty acids metabolisms, which contribute to NAFLD development and its progression in more severe forms, such as cirrhosis; (3) therapy for cirrhosis through dysbiosis reduction, and research on hepatic encephalopathy a common consequence of cirrhosis; (4) evaluation of diversity, and composition of gut microbiome under NAFLD, and as it varies under NASH and cirrhosis by rRNA gene sequencing, a tool which can also be used for the development of new probiotics and explore into the impact of biotics on the gut microbiome; (5) treatments to reduce dysbiosis with new probiotics, such as Akkermansia, or with fecal microbiome transplantation.}, }
@article {pmid37235836, year = {2023}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Kazadi, D and Halaweish, H and Khan, MH and Hoeschen, A and Cao, Q and Luo, X and Kabage, AJ and Lopez, S and Holtan, SG and Weisdorf, DJ and Khoruts, A and Staley, C}, title = {Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {41}, number = {34}, pages = {5306-5319}, pmid = {37235836}, issn = {1527-7755}, support = {KL2 TR002492/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Double-Blind Method ; *Leukemia, Myeloid, Acute/therapy ; Treatment Outcome ; Feces/microbiology ; }, abstract = {PURPOSE: Gut microbiota injury in allogeneic hematopoietic cell transplantation (HCT) recipients and patients with AML has been associated with adverse clinical outcomes. Previous studies in these patients have shown improvements in various microbiome indices after fecal microbiota transplantation (FMT). However, whether microbiome improvements translate into improved clinical outcomes remains unclear. We examined this question in a randomized, double-blind, placebo-controlled phase II trial.<br><br>METHODS: Two independent cohorts of allogeneic HCT recipients and patients with AML receiving induction chemotherapy were randomly assigned in a 2:1 ratio to receive standardized oral encapsulated FMT versus placebo upon neutrophil recovery. After each course of antibacterial antibiotics, patients received a study treatment. Up to three treatments were administered within 3 months. The primary end point was 4-month all-cause infection rate. Patients were followed for 9 months.<br><br>RESULTS: In the HCT cohort (74 patients), 4-month infection density was 0.74 and 0.91 events per 100 patient-days in FMT and placebo arms, respectively (infection rate ratio, 0.83; 95% CI, 0.48 to 1.42; P = .49). In the AML cohort (26 patients), 4-month infection density was 0.93 in the FMT arm and 1.25 in the placebo arm, with an infection rate ratio of 0.74 (95% CI, 0.32 to 1.71; P = .48). Unique donor bacterial sequences comprised 25%-30% of the fecal microbiota after FMT. FMT improved postantibiotic recovery of microbiota diversity, restored several depleted obligate anaerobic commensals, and reduced the abundance of expanded genera Enterococcus, Streptococcus, Veillonella, and Dialister.<br><br>CONCLUSION: In allogeneic HCT recipients and patients with AML, third-party FMT was safe and ameliorated intestinal dysbiosis, but did not decrease infections. Novel findings from this trial will inform future development of FMT trials.}, }
@article {pmid37235073, year = {2023}, author = {Nagarakanti, S and Orenstein, R}, title = {Treating Clostridioides difficile: Could Microbiota-based Live Biotherapeutic Products Provide the Answer?.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {3137-3143}, pmid = {37235073}, issn = {1178-6973}, abstract = {Clostridioides difficile infection (CDI) is a pressing health care issue due to the limited effectiveness of current treatments and high recurrence rates. Current available antibiotic options for CDI disrupt the fecal microbiome which predisposes recurrent CDI. Fecal microbiota transplantation (FMT) has improved the outcomes of recurrent CDI, but concerns surrounding the safety and standardization of the product persist. Microbiota-based live biotherapeutic products (LBPs), are emerging as potential alternatives to FMT for CDI treatment. This review explores the potential of LBPs as safe and effective therapy for CDI. While preclinical and early clinical studies have shown promising results, further research is necessary to determine the optimal composition and dosage of LBPs and to ensure their safety and efficacy in clinical practice. Overall, LBPs hold great promise as a novel therapy for CDI and warrant further investigation in other conditions related to disruption of the colonic microbiota.}, }
@article {pmid37234168, year = {2023}, author = {Yang, Y and He, J and Wang, Y and Liang, L and Zhang, Z and Tan, X and Tao, S and Wu, Z and Dong, M and Zheng, J and Zhang, H and Feng, S and Cheng, W and Chen, Q and Wei, H}, title = {Whole intestinal microbiota transplantation is more effective than fecal microbiota transplantation in reducing the susceptibility of DSS-induced germ-free mice colitis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1143526}, pmid = {37234168}, issn = {1664-3224}, mesh = {Animals ; Mice ; Fecal Microbiota Transplantation/methods ; Interleukin-10 ; *Colitis/chemically induced/therapy/microbiology ; Cytokines/metabolism ; *Inflammatory Bowel Diseases ; Arginine ; }, abstract = {Fecal microbiota transplantation (FMT) is an emerging and effective therapy for the treatment of inflammatory bowel disease (IBD). Previous studies have reported that compared with FMT, whole intestinal microbiota transplantation (WIMT) can more precisely replicate the community structure and reduce the inflammatory response of the host. However, it remains unclear whether WIMT is more effective in alleviating IBD. To examine the efficacy of WIMT and FMT in the intervention of IBD, GF (Germ-free) BALB/c mice were pre-colonized with whole intestinal microbiota or fecal microbiota before being treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by both WIMT and FMT, as demonstrated by the prevention of body weight loss and decreased the Disease activity index and histological scores in mice. However, WIMT's anti-inflammatory effect was superior to that of FMT. In addition, the inflammatory markers myeloperoxidase (MPO) and eosinophil peroxidase were dramatically downregulated by WIMT and FMT. Furthermore, the use of two different types of donors facilitated the regulation of cytokine homeostasis in colitis mice; the level of the pro-inflammatory cytokine IL-1β in the WIMT group was significantly lower than that in the FMT group, while the level of the anti-inflammatory factor IL-10 was significantly higher than that in the FMT group. Both groups showed enhanced expression of occludin to protect the intestinal barrier in comparison with the DSS group, and the WIMT group demonstrated considerably increased levels of ZO-1. The sequencing results showed that the WIMT group was highly enriched in Bifidobacterium, whereas the FMT group was significantly enriched in Lactobacillus and Ochrobactrum. Correlation analysis revealed that Bifidobacterium was negatively correlated with TNF-α, whereas Ochrobactrum was positively correlated with MPO and negatively correlated with IL-10, which might be related to different efficacies. Functional prediction using PICRUSt2 revealed that the FMT group was considerably enriched in the L-arginine biosynthesis I and L-arginine biosynthesis IV pathway, whereas the WIMT group was enriched in the L-lysine fermentation to acetate and butanoate pathway. In conclusion, the symptoms of colitis were subsided to varying degrees by the two different types of donors, with the WIMT group being more effective than the FMT group. This study provides new information on clinical interventions for IBD.}, }
@article {pmid37232579, year = {2023}, author = {Levast, B and Fontaine, M and Nancey, S and Dechelotte, P and Doré, J and Lehert, P}, title = {Single-Donor and Pooling Strategies for Fecal Microbiota Transfer Product Preparation in Ulcerative Colitis: A Systematic Review and Meta-analysis.}, journal = {Clinical and translational gastroenterology}, volume = {14}, number = {5}, pages = {e00568}, pmid = {37232579}, issn = {2155-384X}, mesh = {Humans ; *Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation/methods ; *Microbiota ; Remission Induction ; }, abstract = {INTRODUCTION: Patients with ulcerative colitis (UC) have a less diverse microbiome than healthy subjects. Multiple studies have evaluated fecal microbiota transfer (FMT) in these patients using different methods of product preparation, doses, and routes of administration. A systematic review and meta-analysis was performed to compare the efficacy of single-donor (SDN) and multidonor (MDN) strategies for product preparation.<br><br>METHODS: Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence for studies comparing FMT products manufactured using SDN or MDN strategies to placebo in patients with UC. Fourteen controlled studies were selected for meta-analysis (10 randomized and 4 nonrandomized). The treatment response was assessed by using fixed- and random-effects models, and the significance of the indirect difference between the interventions was assessed using a network approach.<br><br>RESULTS: Considering all 14 studies, MDN and SDN were superior to placebo in terms of treatment response (risk ratios [RRs]: 4.41 and 1.57, respectively [P &#x2264; 0.001 for both]), and MDN was superior to SDN (RR: 2.81, P = 0.005). Meta-analysis of the 10 studies with high quality of evidence showed that MDN was superior to SDN in terms of treatment response (RR: 2.31, P = 0.042). Results were identical for both models.<br><br>DISCUSSION: There was a significant clinical benefit (remission) for patients with UC who received FMT with products manufactured by MDN strategies. Reduction of donor effect may lead to a gain in microbial diversity that could improve response to treatment. These results may have implications in the treatment approach of other diseases amenable to microbiome manipulation.JOURNAL/cltg/04.03/01720094-202305000-00002/2FFU1/v/2023-05-23T220055Z/r/image-tiff.}, }
@article {pmid37231259, year = {2024}, author = {Pinto, Y and Chakraborty, M and Jain, N and Bhatt, AS}, title = {Phage-inclusive profiling of human gut microbiomes with Phanta.}, journal = {Nature biotechnology}, volume = {42}, number = {4}, pages = {651-662}, pmid = {37231259}, issn = {1546-1696}, support = {R01AI14862302//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R01AI14375702//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; 1S10OD02014101//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; 5T32HG000044-25//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; n/a//EIF | Stand Up To Cancer (SU2C)/ ; n/a//Alfred P. Sloan Foundation/ ; Dean's Fellowship//SU | School of Medicine, Stanford University (Stanford School of Medicine, Stanford University)/ ; NDSEG fellowship//U.S. Department of Defense (United States Department of Defense)/ ; }, mesh = {Adult ; Humans ; *Bacteriophages/genetics ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; *Viruses/genetics ; DNA Viruses/genetics ; }, abstract = {Due to technical limitations, most gut microbiome studies have focused on prokaryotes, overlooking viruses. Phanta, a virome-inclusive gut microbiome profiling tool, overcomes the limitations of assembly-based viral profiling methods by using customized k-mer-based classification tools and incorporating recently published catalogs of gut viral genomes. Phanta's optimizations consider the small genome size of viruses, sequence homology with prokaryotes and interactions with other gut microbes. Extensive testing of Phanta on simulated data demonstrates that it quickly and accurately quantifies prokaryotes and viruses. When applied to 245 fecal metagenomes from healthy adults, Phanta identifies ~200 viral species per sample, ~5× more than standard assembly-based methods. We observe a ~2:1 ratio between DNA viruses and bacteria, with higher interindividual variability of the gut virome compared to the gut bacteriome. In another cohort, we observe that Phanta performs equally well on bulk versus virus-enriched metagenomes, making it possible to study prokaryotes and viruses in a single experiment, with a single analysis.}, }
@article {pmid37230956, year = {2023}, author = {Song, Y and Cui, Y and Wang, Y and Yu, J and Wang, B and Wen, Q and Zheng, X}, title = {Donor selection for fecal bacterial transplantation and its combined effects with inulin on early growth and ileal development in chicks.}, journal = {Journal of applied microbiology}, volume = {134}, number = {5}, pages = {}, doi = {10.1093/jambio/lxad099}, pmid = {37230956}, issn = {1365-2672}, support = {21ZGN16//Changchun Key Research and Development Program/ ; }, mesh = {Humans ; Animals ; Female ; *Fecal Microbiota Transplantation/methods ; *Inulin/pharmacology ; Donor Selection ; Chickens ; Feces/microbiology ; Bacteria ; }, abstract = {AIMS: To select the best donor and investigate its combined effects with inulin on growth performance, and ileal health of chicks.<br><br>METHODS AND RESULTS: The chicks (Hy-line Brown) were treated with fecal microbiota suspension from different breeder hens to select the best donor. Treatment with fecal microbiota transplantation (FMT) alone or in combination with inulin resulted in improvement in gut microbiome in chicks. The organ indexes were improved on day 7, especially the bursa of fabricius index (P&#xa0;<&#xa0;0.05). On day 14, immune performance, ileal morphology, and barrier were improved, and simultaneously, the concentration of short-chain fatty acids was also increased. In addition, for the expression of ileal barrier-related genes, Anaerofustis and Clostridium were positively correlated with them (P&#xa0;<&#xa0;0.05), Blautia, Prevotella, Veillonella, and Weissella showed a negative correlation (P&#xa0;<&#xa0;0.05), and RFN20 showed a positive correlation with gut morphology (P&#xa0;<&#xa0;0.05).<br><br>CONCLUSION: Combination of homologous FMT and inulin promoted early growth and intestinal health of chicks.}, }
@article {pmid37229456, year = {2023}, author = {Wu, J and Yang, K and Fan, H and Wei, M and Xiong, Q}, title = {Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1114424}, pmid = {37229456}, issn = {1664-2392}, mesh = {Humans ; *Diabetes Mellitus, Type 2/therapy/metabolism ; *Gastrointestinal Microbiome ; Prebiotics ; *Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and insulin resistance. The incidence of T2DM is increasing globally, and a growing body of evidence suggests that gut microbiota dysbiosis may contribute to the development of this disease. Gut microbiota-derived metabolites, including bile acids, lipopolysaccharide, trimethylamine-N-oxide, tryptophan and indole derivatives, and short-chain fatty acids, have been shown to be involved in the pathogenesis of T2DM, playing a key role in the host-microbe crosstalk. This review aims to summarize the molecular links between gut microbiota-derived metabolites and the pathogenesis of T2DM. Additionally, we review the potential therapy and treatments for T2DM using probiotics, prebiotics, fecal microbiota transplantation and other methods to modulate gut microbiota and its metabolites. Clinical trials investigating the role of gut microbiota and its metabolites have been critically discussed. This review highlights that targeting the gut microbiota and its metabolites could be a potential therapeutic strategy for the prevention and treatment of T2DM.}, }
@article {pmid37229259, year = {2023}, author = {Li, HJ and Li, DQ and Zhang, YL and Ding, XF and Gao, HT and Zhu, Y and Liu, J and Zhang, LX and Chen, J and Chen, G and Yu, Y}, title = {Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1123387}, pmid = {37229259}, issn = {1663-9812}, abstract = {Gut microbiota affects the gut-brain axis; hence, the modulation of the microbiota has been proposed as a potential therapeutic strategy for cerebral ischemia/reperfusion injury (CIRI). However, the role and mechanism of the gut microbiota in regulating microglial polarization during CIRI remain poorly understood. Herein, using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model, we evaluated changes in the gut microbiota after CIRI and the potential effects of fecal microbiota transplant (FMT) on the brain. Rats underwent either MCAO/R or sham surgery, and then they received FMT (started 3 days later; continued for 10 days). 2,3,5-Triphenyltetrazolium chloride staining, neurological outcome scale, and Fluoro-Jade C staining showed that MCAO/R induced cerebral infarction, neurological deficits, and neuronal degeneration. In addition, immunohistochemistry or real-time PCR assay showed increased expression levels of M1-macrophage markers-TNF-α, IL-1β, IL-6, and iNOS-in the rats following MCAO/R. Our finding suggests that microglial M1 polarization is involved in CIRI. 16 S ribosomal RNA gene sequencing data revealed an imbalance in the gut microbiota of MCAO/R animals. In contrast, FMT reversed this MCAO/R-induced imbalance in the gut microbiota and ameliorated nerve injury. In addition, FMT prevented the upregulation in the ERK and NF-κB pathways, which reversed the M2-to-M1 microglial shift 10 days after MCAO/R injury in rats. Our primary data showed that the modulation of the gut microbiota can attenuate CIRI in rats by inhibiting microglial M1 polarization through the ERK and NF-κB pathways. However, an understanding of the underlying mechanism requires further study.}, }
@article {pmid37228365, year = {2023}, author = {Wang, R}, title = {Clostridioides difficile infection: microbe-microbe interactions and live biotherapeutics.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1182612}, pmid = {37228365}, issn = {1664-302X}, abstract = {Clostridioides difficile is a gram-positive, spore-forming, obligate anaerobe that infects the colon. C. difficile is estimated to cause nearly half a million cases in the United States annually, with about 29,000 associated deaths. Unfortunately, the current antibiotic treatment is not ideal. While antibiotics can treat the infections, they also disrupt the gut microbiota that mediates colonization resistance against enteric pathogens, including C. difficile; disrupted gut microbiota provides a window of opportunity for recurrent infections. Therefore, therapeutics that restore the gut microbiota and suppress C. difficile are being evaluated for safety and efficacy. This review will start with mechanisms by which gut bacteria affect C. difficile pathogenesis, followed by a discussion on biotherapeutics for recurrent C. difficile infections.}, }
@article {pmid37227445, year = {2023}, author = {Luo, Q and Gong, P and Shi, R and Chen, W and Wang, C and Zhang, C and Wu, Z}, title = {Syringic Acid Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {22}, pages = {8458-8470}, doi = {10.1021/acs.jafc.3c02441}, pmid = {37227445}, issn = {1520-5118}, mesh = {Animals ; Mice ; Dextran Sulfate/adverse effects ; *Gastrointestinal Microbiome ; *Colitis/chemically induced/drug therapy/metabolism ; Colon/metabolism ; *Inflammatory Bowel Diseases ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {Inflammatory bowel disease is known to be associated with alterations in gut microbiota. The bioactive compound syringic acid has been shown to alleviate inflammatory bowel disease, but its interaction with gut microbiota and mechanism of action remain unclear. To address this, we conducted a study in which we investigated the potential benefits of syringic acid in a mouse model of dextran sulfate sodium-induced colitis through gut microbiota modulation. Our results show that oral administration of syringic acid effectively reduced symptoms of colitis, as indicated by reduced disease activity index, and histopathology scores. Moreover, syringic acid administration enriched the abundance of Alistipes and norank_f__norank_o__Gastranaerophilales in mice, suggesting a restoration of impaired gut microbiota. Notably, we found that the effects of syringic acid were similar to those of fecal microbiota transplantation in dextran sulfate sodium-induced mice. Further analysis revealed that syringic acid inhibited the NLRP3-Cas-1-GSDMD-IL-1β inflammatory vesicle signaling pathway, leading to amelioration of colonic inflammation in a gut microbiota-dependent manner. Our findings demonstrate the potential of syringic acid as a preventive and therapeutic agent for inflammatory bowel disease.}, }
@article {pmid37223860, year = {2023}, author = {Geng, Y and Shi, T and Wang, Y}, title = {Transmission of Hepatitis E Virus.}, journal = {Advances in experimental medicine and biology}, volume = {1417}, number = {}, pages = {73-92}, pmid = {37223860}, issn = {0065-2598}, mesh = {Animals ; Humans ; *Hepatitis E virus/genetics ; Infectious Disease Transmission, Vertical ; Africa ; Asia ; *Epidemics ; }, abstract = {Transmission of hepatitis E virus (HEV) occurs predominantly by the fecal-oral route. Large epidemics of hepatitis E in the developing countries of Asia and Africa are waterborne and spread through contaminated drinking water. The reservoir of HEV in developed countries is believed to be in animals with zoonotic transmission to humans, possibly through direct contact or the consumption of undercooked contaminated meat. And HEV transmission through blood transfusion, organ transplantation, and vertical transmission has been reported.}, }
@article {pmid37222345, year = {2023}, author = {Barbosa, EC and Bucar, EEC and Jubé, GR and Silveira, LB and Silva, NCD and Faria, PCC and Ramos, PLC and Moraes, VRY and Barros, JOB}, title = {Fecal microbiota transplantation and its repercussions in patients with melanoma refractory to anti-PD-1 therapy: scope review.}, journal = {Revista do Colegio Brasileiro de Cirurgioes}, volume = {50}, number = {}, pages = {e20233490}, pmid = {37222345}, issn = {1809-4546}, mesh = {Humans ; *Melanoma ; Fecal Microbiota Transplantation ; }, abstract = {INTRODUCTION: despite being extremely effective in some cases, up to 70% of patients with melanoma do not respond to anti-PD-1/PD-L1 (primary resistance) and many of the responders eventually progress (secondary resistance). Extensive efforts are being made to overcome this resistance through new strategies, especially aimed at modulating the intestinal microbiota.<br><br>OBJECTIVE: to assess whether fecal microbiota transplantation (FMT), associated with immunotherapy, is beneficial in the clinical course of patients with refractory melanoma.<br><br>METHODS: this is a scope review, based on studies collected on the MEDLINE, ScienceDirect, The Cochrane Library, Embase and BMJ Journals; using the terms: "Antibodies, Monoclonal"; "Drug Resistance, Neoplasm"; "Fecal Microbiota Transplantation"; "Host Microbial Interactions"; "Immunotherapy"; "Melanoma"; and "Microbiota". Clinical trials, in English, with relevant data on the subject and fully available were included. A cut-off period was not determined, due to the limited amount of evidence on the topic.<br><br>RESULTS: crossing the descriptors allowed the identification of 342 publications and, after applying the eligibility criteria, allowed the selection of 4 studies. From the analyses, it was observed that a considerable part of those studied overcame resistance to immune checkpoint inhibitors after FMT, with better response to treatment, less tumor growth and increased beneficial immune response.<br><br>CONCLUSION: it is noted that FMT favors the response of melanoma to immunotherapy, translated into significant clinical benefit. However, further studies are necessary for the complete elucidation of the bacteria and the mechanisms involved, as well as for the translation of new evidence to oncological care practice.}, }
@article {pmid37221272, year = {2023}, author = {Hsia, K and Zhao, N and Chung, M and Algarrahi, K and Montaser Kouhsari, L and Fu, M and Chen, H and Singh, S and Michaud, DS and Jangi, S}, title = {Alterations in the Fungal Microbiome in Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {29}, number = {10}, pages = {1613-1621}, pmid = {37221272}, issn = {1536-4844}, support = {KL2 TR002545/TR/NCATS NIH HHS/United States ; R01 DK135937/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Humans ; *Colitis, Ulcerative/therapy ; *Mycobiome ; Prospective Studies ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/microbiology ; Candida ; *Biological Products ; }, abstract = {BACKGROUND: Although gut fungi have been implicated in the immunopathogenesis of inflammatory bowel disease, the fungal microbiome has not been deeply explored across endohistologic activity and treatment exposure in ulcerative colitis.<br><br>METHODS: We analyzed data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry. We evaluated the fungal composition of fecal samples from 98 patients with ulcerative colitis across endoscopic activity (n&#x2005;=&#x2005;43), endohistologic activity (n&#x2005;=&#x2005;41), and biologic exposure (n&#x2005;=&#x2005;82). Across all subgroups, we assessed fungal diversity and differential abundance of taxonomic groups.<br><br>RESULTS: We identified 500 unique fungal amplicon sequence variants across the cohort of 82 patients, dominated by phylum Ascomycota. Compared with endoscopic remission, patients with endoscopic activity had increased Saccharomyces (log2 fold change = 4.54; adjusted P&#x2005;<&#x2005;5&#x2005;&#xd7;&#x2005;10-5) and increased Candida (log2 fold change = 2.56; adjusted P&#x2005;<&#x2005;.03). After adjusting for age, sex, and biologic exposure among patients with endoscopic activity, Saccharomyces (log2 fold change = 7.76; adjusted P <&#x2005;1&#x2005;&#xd7;&#x2005;10-15) and Candida (log2 fold change = 7.28; adjusted P<&#x2005;1&#x2005;&#xd7;&#x2005;10-8) remained enriched during endoscopic activity compared with quiescence.<br><br>CONCLUSIONS: Endoscopic inflammation in ulcerative colitis is associated with an expansion of Saccharomyces and Candida compared with remission. The role of these fungal taxa as potential biomarkers and targets for personalized approaches to therapeutics in ulcerative colitis should be evaluated.}, }
@article {pmid37221233, year = {2023}, author = {Carvalho, T}, title = {First oral fecal microbiota transplant therapy approved.}, journal = {Nature medicine}, volume = {29}, number = {7}, pages = {1581-1582}, doi = {10.1038/d41591-023-00046-2}, pmid = {37221233}, issn = {1546-170X}, mesh = {*Fecal Microbiota Transplantation ; }, }
@article {pmid37220623, year = {2023}, author = {Benichou Haziot, C and Birak, KS}, title = {Therapeutic Potential of Microbiota Modulation in Alzheimer's Disease: A Review of Preclinical Studies.}, journal = {Journal of Alzheimer's disease reports}, volume = {7}, number = {1}, pages = {415-431}, pmid = {37220623}, issn = {2542-4823}, abstract = {Alzheimer's disease (AD) is the most common neurodegenerative disease, yet it currently lacks effective treatment due to its complex etiology. The pathological changes in AD have been linked to the neurotoxic immune responses following aggregation of Aβ and phosphorylated tau. The gut microbiota (GM) is increasingly studied for modulating neuroinflammation in neurodegenerative diseases and in vivo studies emerge for AD. This critical review selected 7 empirical preclinical studies from 2019 onwards assessing therapy approaches targeting GM modulating microglia neuroinflammation in AD mouse models. Results from probiotics, fecal microbiota transplantation, and drugs were compared and contrasted, including for cognition, neuroinflammation, and toxic aggregation of proteins. Studies consistently reported significant amelioration or prevention of cognitive deficits, decrease in microglial activation, and lower levels of pro-inflammatory cytokines, compared to AD mouse models. However, there were differences across papers for the brain regions affected, and changes in astrocytes were inconsistent. Aβ plaques deposition significantly decreased in all papers, apart from Byur dMar Nyer lNga Ril Bu (BdNlRB) treatment. Tau phosphorylation significantly declined in 5 studies. Effects in microbial diversity following treatment varied across studies. Findings are encouraging regarding the efficacy of study but information on the effect size is limited. Potentially, GM reverses GM derived abnormalities, decreasing neuroinflammation, which reduces AD toxic aggregations of proteins in the brain, resulting in cognitive improvements. Results support the hypothesis of AD being a multifactorial disease and the potential synergies through multi-target approaches. The use of AD mice models limits conclusions around effectiveness, as human translation is challenging.}, }
@article {pmid37219936, year = {2023}, author = {Luo, Y and Tong, Y and Wu, L and Niu, H and Li, Y and Su, LC and Wu, Y and Bozec, A and Zaiss, MM and Qing, P and Zhao, H and Tan, C and Zhang, Q and Zhao, Y and Tang, H and Liu, Y}, title = {Alteration of Gut Microbiota in Individuals at High-Risk for Rheumatoid Arthritis Associated With Disturbed Metabolome and the Initiation of Arthritis Through the Triggering of Mucosal Immunity Imbalance.}, journal = {Arthritis &amp; rheumatology (Hoboken, N.J.)}, volume = {75}, number = {10}, pages = {1736-1748}, doi = {10.1002/art.42616}, pmid = {37219936}, issn = {2326-5205}, mesh = {Humans ; Mice ; Animals ; *Gastrointestinal Microbiome/genetics ; Immunity, Mucosal ; Caco-2 Cells ; *Arthritis, Rheumatoid ; *Arthritis, Experimental ; Metabolome ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVE: In this study, we aimed to decipher the gut microbiome (GM) and serum metabolic characteristic of individuals at high risk for rheumatoid arthritis (RA) and to investigate the causative effect of GM on the mucosal immune system and its involvement in the pathogenesis of arthritis.<br><br>METHODS: Fecal samples were collected from 38 healthy individuals and 53 high-risk RA individuals with anti-citrullinated protein antibody (ACPA) positivity (Pre-RA), 12 of 53 Pre-RA individuals developed RA within 5&#x2009;years of follow-up. The differences in intestinal microbial composition between the healthy controls and Pre-RA individuals or among Pre-RA subgroups were identified by 16S ribosomal RNA sequencing. The serum metabolite profile and its correlation with GM were also explored. Moreover, antibiotic-pretreated mice that received GM from the healthy control or Pre-RA groups were then evaluated for intestinal permeability, inflammatory cytokines, and immune cell populations. Collagen-induced arthritis (CIA) was also applied to test the effect of fecal microbiota transplantation (FMT) from Pre-RA individuals on arthritis severity in mice.<br><br>RESULTS: Stool microbial diversity was lower in Pre-RA individuals than in healthy controls. The bacterial community structure and function significantly differed between healthy controls and Pre-RA individuals. Although there were differences to some extent in the bacterial abundance among the Pre-RA subgroups, no robust functional differences were observed. The metabolites in the serum of the Pre-RA group were dramatically different from those in the healthy controls group, with KEGG pathway enrichment of amino acid and lipid metabolism. Moreover, intestinal bacteria from the Pre-RA group increased intestinal permeability in FMT mice and zonula occludens-1 expression in the small intestine and Caco-2 cells. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer's patches were also increased in mice receiving Pre-RA feces compared to healthy controls. The changes in intestinal permeability and Th17-cell activation prior to arthritis induction enhanced CIA severity in PreRA-FMT mice compared with HC-FMT mice.<br><br>CONCLUSION: Gut microbial dysbiosis and metabolome alterations already occur in individuals at high risk for RA. FMT from preclinical individuals triggers intestinal barrier dysfunction and changes mucosal immunity, further contributing to the development of arthritis.}, }
@article {pmid37218816, year = {2023}, author = {Merrick, B and Sergaki, C and Edwards, L and Moyes, DL and Kertanegara, M and Prossomariti, D and Shawcross, DL and Goldenberg, SD}, title = {Modulation of the Gut Microbiota to Control Antimicrobial Resistance (AMR)-A Narrative Review with a Focus on Faecal Microbiota Transplantation (FMT).}, journal = {Infectious disease reports}, volume = {15}, number = {3}, pages = {238-254}, pmid = {37218816}, issn = {2036-7430}, abstract = {Antimicrobial resistance (AMR) is one of the greatest challenges facing humanity, causing a substantial burden to the global healthcare system. AMR in Gram-negative organisms is particularly concerning due to a dramatic rise in infections caused by extended-spectrum beta-lactamase and carbapenemase-producing Enterobacterales (ESBL and CPE). These pathogens have limited treatment options and are associated with poor clinical outcomes, including high mortality rates. The microbiota of the gastrointestinal tract acts as a major reservoir of antibiotic resistance genes (the resistome), and the environment facilitates intra and inter-species transfer of mobile genetic elements carrying these resistance genes. As colonisation often precedes infection, strategies to manipulate the resistome to limit endogenous infections with AMR organisms, as well as prevent transmission to others, is a worthwhile pursuit. This narrative review presents existing evidence on how manipulation of the gut microbiota can be exploited to therapeutically restore colonisation resistance using a number of methods, including diet, probiotics, bacteriophages and faecal microbiota transplantation (FMT).}, }
@article {pmid37217962, year = {2023}, author = {Wang, C and Lin, Y and Chen, L and Chen, H}, title = {Gut microbiota mediated the effects of high relative humidity on lupus in female MRL/lpr mice.}, journal = {Advances in rheumatology (London, England)}, volume = {63}, number = {1}, pages = {24}, pmid = {37217962}, issn = {2523-3106}, mesh = {Animals ; Mice ; Male ; Female ; Humans ; Mice, Inbred MRL lpr ; *Gastrointestinal Microbiome ; Humidity ; *Lupus Erythematosus, Systemic/therapy/pathology ; Kidney/pathology ; }, abstract = {INTRODUCTION: The relationship between humidity and systemic lupus erythematosus (SLE) has yielded inconsistent results in prior research, while the effects of humidity on lupus in animal experiments and its underlying mechanism remain inadequately explored.<br><br>METHODS: The present study aimed to investigate the impact of high humidity (80&#x2009;&#xb1;&#x2009;5%) on lupus using female and male MRL/lpr mice, with a particular focus on elucidating the role of gut microbiota in this process. To this end, fecal microbiota transplantation (FMT) was employed to transfer the gut microbiota of MRL/lpr mice under high humidity to blank MRL/lpr mice under normal humidity (50&#x2009;&#xb1;&#x2009;5%), allowing for an assessment of the effect of FMT on lupus.<br><br>RESULTS: The study revealed that high humidity exacerbated lupus indices (serum anti-dsDNA, ANA, IL-6, and IFN- g, and renal pathology) in female MRL/lpr mice but had no significant effect on male MRL/lpr mice. The aggravation of lupus caused by high humidity may be attributed to the increased abundances of the Rikenella, Romboutsia, Turicibacter, and Escherichia-Shigella genera in female MRL/lpr mice. Furthermore, FMT also exacerbated lupus in female MRL/lpr mice but not in male MRL/lpr mice.<br><br>CONCLUSION: In summary, this study has demonstrated that high humidity exacerbated lupus by modulating gut microbiota in female MRL/lpr mice. The findings underscore the importance of considering environmental factors and gut microbiota in the development and progression of lupus, particularly among female patients.}, }
@article {pmid37217087, year = {2023}, author = {Fu, C and Ni, J and Huang, R and Gao, Y and Li, S and Li, Y and JinjinLi,  and Zhong, K and Zhang, P}, title = {Sex different effect of antibiotic and probiotic treatment on intestinal microbiota composition in chemically induced liver injury rats.}, journal = {Genomics}, volume = {115}, number = {4}, pages = {110647}, doi = {10.1016/j.ygeno.2023.110647}, pmid = {37217087}, issn = {1089-8646}, mesh = {Female ; Male ; Rats ; Animals ; Anti-Bacterial Agents/pharmacology ; *Gastrointestinal Microbiome ; *Chemical and Drug Induced Liver Injury, Chronic ; Diethylnitrosamine/pharmacology ; Sex Characteristics ; *Probiotics ; }, abstract = {Differences in the gut microbiota and metabolic processes between males and females may explain differences in the risk of liver injury; however, the sex-specific effects of antibiotics and probiotics on these relationships are not clear. We evaluated differences in the gut microbiota and the risk of liver injury between male and female rats after the oral administration of antibiotics or probiotics followed by a period of diethylnitrosamine treatment to chemically induce liver injuryusing high-throughput sequencing of fecal microbiota combined with histological analyses of liver and colon tissues. Our results suggest that the ratio of gram-positive to gram-negative bacteria in kanamycin-treated rats was significantly higher than that of other groups, and this difference persisted for the duration of the experiment. Antibiotics significantly changed the composition of the gut microbiota of experimental rats. Clindamycin caused more diethylnitrosamine-induced damage to livers of male rats. Probiotics did not influencethe gut microbiota; however, they hadprotective effects against liver injury induced by diethylnitrosamine, especially in female rats. These results strengthen our understanding of sex differences in the indirect effects of antibiotics or probiotics on metabolism and liver injury in hosts via the gut microbiota.}, }
@article {pmid37216694, year = {2023}, author = {Strassmann, V and Silva-Alvarenga, E and Emile, SH and Garoufalia, Z and DaSilva, G and Wexner, SD}, title = {Gracilis Muscle Interposition: A Valuable Tool for the Treatment of Failed Repair of Post-partum Rectovaginal Fistulas-A Single-Center Experience.}, journal = {The American surgeon}, volume = {89}, number = {12}, pages = {6366-6369}, doi = {10.1177/00031348231175481}, pmid = {37216694}, issn = {1555-9823}, mesh = {Female ; Humans ; Adult ; Rectovaginal Fistula/etiology/surgery ; Retrospective Studies ; *Gracilis Muscle/transplantation ; Surgical Flaps/transplantation ; *Rectal Fistula/surgery ; Postoperative Complications/surgery ; Postpartum Period ; Treatment Outcome ; }, abstract = {INTRODUCTION: Rectovaginal fistulas (RVFs) account for approximately 40% of anorectal complications from obstetrical trauma. Treatment can be challenging requiring multiple surgical repairs. Interposition of healthy transposed tissue (lotus or Martius flap or gracilis muscle) has been used for recurrent RVF. We aimed to review our experience with gracilis muscle interposition (GMI) for post-partum RVF.<br><br>METHODS: A retrospective analysis of patients who underwent GMI for post-partum RVF from February 1995 to December 2019 was undertaken. Patient demographics, number of prior treatments, comorbidities, tobacco use, postoperative complications, additional procedures, and outcome were assessed. Success was defined as absence of leakage from the repair site after stoma reversal.<br><br>RESULTS: Six of 119 patients who underwent GMI did so for recurrent post-partum RVF. Median age was 34.2 (28-48) years. All patients had at least 1 previously failed procedure [median: 3 (1-7)] including endorectal advancement flap, fistulotomy, vaginoplasty, mesh interposition, and sphincteroplasty. All patients underwent fecal diversion prior to or at initial procedure. Success was achieved in 4/6 (66.7%) patients; 2 underwent further procedures (1 fistulotomy and 1 rectal flap advancement) for a final 100% success rate as all ileostomies were reversed. Morbidity was reported in 3 (50%) patients, including wound dehiscence, delayed rectoperineal fistula, and granuloma formation in one each, all managed without surgery. There was no morbidity related to stoma closure.<br><br>CONCLUSIONS: Gracilis muscle interposition is a valuable tool for recurrent post-partum RVF. Our ultimate success rate in this very small series was 100% with a relatively low morbidity rate.}, }
@article {pmid37216289, year = {2023}, author = {Groenewegen, B and Terveer, EM and Joosse, A and Barnhoorn, MC and Zwittink, RD}, title = {Fecal Microbiota Transplantation for Immune Checkpoint Inhibitor-Induced Colitis Is Safe and Contributes to Recovery: Two Case Reports.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {46}, number = {6}, pages = {216-220}, doi = {10.1097/CJI.0000000000000474}, pmid = {37216289}, issn = {1537-4513}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; Immune Checkpoint Inhibitors/adverse effects ; Feces/microbiology ; *Colitis/diagnosis/etiology/therapy ; Bacteria ; Leukocyte L1 Antigen Complex ; Treatment Outcome ; }, abstract = {Immune checkpoint inhibitors (ICIs) have improved the prognosis in multiple cancer types. However, ICIs can induce immune-related adverse events such as immune-mediated enterocolitis (IMC). The gut microbiota may be implicated in IMC development. Therefore, we investigated fecal microbiota transplantation (FMT) as a treatment option for 2 patients with metastatic cancer suffering from refractory IMC. The patients were treated with, respectively, 1 and 3 FMTs after vancomycin pre-treatment. We monitored defecation frequency, fecal calprotectin, and microbiota composition. After FMT, both patients improved in defecation frequency, were discharged from the hospital, and received lower dosage of immunosuppressive therapy. Patient 1 developed an invasive pulmonary aspergillosis deemed to be related to prolonged steroid exposure. Patient 2 suffered from a Campylobacter jejuni infection after the first FMT and was treated with meropenem, resulting in a low-diversity microbiota profile and increased calprotectin levels and defecation frequency. After a second and third FMT, bacterial diversity increased and defecation frequency and calprotectin levels decreased. Pre-FMT, both patients showed low bacterial richness, but varying bacterial diversity. After FMT, diversity and richness were similar to healthy donor levels. In conclusion, FMT resulted in improvement of IMC symptoms and corresponding microbial changes in 2 cancer patients with refractory IMC. While more research is warranted, microbiome-modulation could be a promising new therapeutic option for IMC.}, }
@article {pmid37216124, year = {2023}, author = {Markandey, M and Bajaj, A and Verma, M and Virmani, S and Singh, MK and Gaur, P and Das, P and Srikanth, CV and Makharia, G and Kedia, S and Ahuja, V}, title = {Fecal microbiota transplantation refurbishes the crypt-associated microbiota in ulcerative colitis.}, journal = {iScience}, volume = {26}, number = {5}, pages = {106738}, pmid = {37216124}, issn = {2589-0042}, abstract = {A crypt autochthonous microbial population called crypt-associated microbiota (CAM) is localized intimately with gut regenerative and immune machinery. The present report utilizes laser capture microdissection coupled with 16S amplicon sequencing to characterize the CAM in patients with ulcerative colitis (UC) before and after fecal microbiota transplantation with anti-inflammatory diet (FMT-AID). Compositional differences in CAM and its interactions with mucosa-associated microbiota (MAM) were compared between the non-IBD controls and in patients with UC pre- and post-FMT (n = 26). Distinct from the MAM, CAM is dominated by aerobic members of Actinobacteria and Proteobacteria and exhibits resilience of diversity. CAM underwent UC-associated dysbiosis and demonstrated restoration post-FMT-AID. These FMT-restored CAM taxa correlated negatively with disease activity in patients with UC. The positive effects of FMT-AID extended further in refurbishing CAM-MAM interactions, which were obliterated in UC. These results encourage investigation into host-microbiome interactions established by CAM, to understand their role in disease pathophysiology.}, }
@article {pmid37215136, year = {2023}, author = {Sun, Y and Wang, K and Zhao, W}, title = {Gut microbiota in perioperative neurocognitive disorders: current evidence and future directions.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1178691}, pmid = {37215136}, issn = {1664-3224}, mesh = {Humans ; *Quality of Life ; *Gastrointestinal Microbiome ; Neuroinflammatory Diseases ; Neurocognitive Disorders ; Central Nervous System ; }, abstract = {Perioperative neurocognitive disorders (PND) is a common surgical anesthesia complication characterized by impairment of memory, attention, language understanding and social ability, which can lead to a decline in the quality of life of patients, prolong the hospitalization period and increase the mortality rate. PND has a high incidence rate, which has a great impact on postoperative recovery and quality of life of patients, and has caused a heavy economic burden to society and families. In recent years, PND has become an important public health problem. The high risk population of PND is more prone to gut microbiota imbalance, and gut microbiota may also affect the inflammatory response of the central nervous system through the microbiota-gut-brain axis. Meanwhile, Neuroinflammation and immune activation are important mechanisms of PND. Regulating gut microbiota through probiotics or fecal bacteria transplantation can significantly reduce neuroinflammation, reduce the abnormal activation of immune system and prevent the occurrence of PND. This review summarizes the research progress of gut microbiota and PND, providing basis for the prevention and treatment of PND.}, }
@article {pmid37214858, year = {2023}, author = {Bleich, RM and Li, C and Sun, S and Barlogio, CJ and Broberg, CA and Franks, AR and Bulik-Sullivan, E and Dogan, B and Simpson, KW and Carroll, IM and Fodor, AA and Arthur, JC}, title = {A consortia of clinical E. coli strains with distinct in-vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37214858}, issn = {2693-5015}, support = {K12 GM000678/GM/NIGMS NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in-vitro definition fully predicts mucosal colonization in-vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis.<br><br>RESULTS: Germ-free inflammation-susceptible interleukin-10-deficient (Il10[-/-]) and inflammation-resistant WT mice were colonized with a consortia of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10[-/-] mice. These E. coli expand in Il10[-/-] mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization.<br><br>CONCLUSIONS: Our findings establish the in-vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in-vivo colonization dynamics of patient-derived bacteria in murine models.}, }
@article {pmid37214214, year = {2023}, author = {Yi, W and Huang, Q and Wang, Y and Shan, T}, title = {Lipo-nutritional quality of pork: The lipid composition, regulation, and molecular mechanisms of fatty acid deposition.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {13}, number = {}, pages = {373-385}, pmid = {37214214}, issn = {2405-6383}, abstract = {Pork is one of the main meats consumed by people, and its nutritional value is closely related to human health. The lipid deposition and composition of pork not only affect the sensory quality but also determine the nutritional quality of pork. The lipids in pork include triglycerides (TAG) and a small amount of cholesterol and phospholipids. TAG are the main lipids in skeletal muscle fat, which is divided into intermuscular fat and intramuscular fat (IMF). In addition to TAG, IMF also contains phospholipids, which are important factors affecting pork flavour. There are three types of fatty acids in TAG: saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA). PUFA, such as n-3 PUFA, have a beneficial effect on health, including the regulation of whole-body energy metabolism and protection against cardiovascular diseases. Therefore, regulating lipid deposition, especially the fatty acid composition, in pork is important for improving the nutritional quality for human health. Notably, several strategies, such as breeding, environmental control, and the nutritional regulation of lipid composition and deposition in pork, have been studied. More recently, faecal transplantation, molecular design breeding and non-coding RNA have been studied and proven useful for regulating lipid deposition in pigs. In this review, we mainly summarized and discussed the research findings to date on the lipid composition and regulation mechanisms of fatty acid deposition and provide new insights into efficient means of improving the lipid composition and lipo-nutritional quality of pork.}, }
@article {pmid37213506, year = {2023}, author = {Zhang, Y and Zhang, J and Wu, J and Zhu, Q and Chen, C and Li, Y}, title = {Implications of gut microbiota dysbiosis and fecal metabolite changes in psychologically stressed mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1124454}, pmid = {37213506}, issn = {1664-302X}, abstract = {INTRODUCTION: Psychological stress can induce affective disorders. Gut microbiota plays a vital role in emotional function regulation; however, the association between gut microbiota and psychological stress is poorly understood. We investigated effects of psychological stress on the gut microbiome and fecal metabolites and assessed the relationship between affective disorder behavior and altered fecal microbiota.<br><br>METHODS: A psychological stress model was established in C57BL/6J mice using a communication box. Sucrose preference test, forced swim test, and open field test helped assess anxiety- and depression-like behaviors. Fecal microbiota transplantation (FMT) was conducted using fecal samples from stressed and non-stressed mice. Moreover, 16S rRNA gene sequencing and untargeted metabolomics were performed.<br><br>RESULTS: After stress exposure for 14 days, a significant increase in anxiety- and depression-like behaviors was observed. FMT of "affective disorder microbiota" from psychologically stressed mice increased stress sensitivity relative to FMT of "normal microbiota" from non-stressed mice. 16S rRNA gene sequencing revealed decreased abundance of Bacteroides, Alistipes, and Lactobacillus and increased abundance of Parasutterella and Rikenellaceae_RC9_gut_group in stressed mice; furthermore, stressed mice showed differential metabolite profiles. KEGG pathway analysis indicated that differential metabolites were chiefly involved in the downregulated pathways of &#x3b1;-linolenic acid metabolism, taste transduction, and galactose metabolism. Alistipes and Bacteroides were mainly positively correlated and Parasutterella was mainly negatively correlated with diverse metabolites.<br><br>DISCUSSION: Our findings suggest that gut microbiome dysbiosis contributes to affective disorder development in response to psychological stress.}, }
@article {pmid37213403, year = {2023}, author = {Lahtinen, P and Jalanka, J and Mattila, E and Tillonen, J and Bergman, P and Satokari, R and Arkkila, P}, title = {Fecal microbiota transplantation for the maintenance of remission in patients with ulcerative colitis: A randomized controlled trial.}, journal = {World journal of gastroenterology}, volume = {29}, number = {17}, pages = {2666-2678}, pmid = {37213403}, issn = {2219-2840}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Colitis, Ulcerative/diagnosis/therapy/etiology ; Quality of Life ; Remission Induction ; Feces ; Leukocyte L1 Antigen Complex ; }, abstract = {BACKGROUND: Fecal microbial transplantation (FMT) is a promising new method for treating active ulcerative colitis (UC), but knowledge regarding FMT for quiescent UC is scarce.<br><br>AIM: To investigate FMT for the maintenance of remission in UC patients.<br><br>METHODS: Forty-eight UC patients were randomized to receive a single-dose FMT or autologous transplant via colonoscopy. The primary endpoint was set to the maintenance of remission, a fecal calprotectin level below 200 &#x3bc;g/g, and a clinical Mayo score below three throughout the 12-mo follow-up. As secondary endpoints, we recorded the patient's quality of life, fecal calprotectin, blood chemistry, and endoscopic findings at 12 mo.<br><br>RESULTS: The main endpoint was achieved by 13 out of 24 (54%) patients in the FMT group and by 10 out of 24 (41%) patients in the placebo group (log-rank test, P = 0.660). Four months after FMT, the quality-of-life scores decreased in the FMT group compared to the placebo group (P = 0.017). In addition, the disease-specific quality of life measure was higher in the placebo group than in the FMT group at the same time point (P = 0.003). There were no differences in blood chemistry, fecal calprotectin, or endoscopic findings among the study groups at 12 mo. The adverse events were infrequent, mild, and distributed equally between the groups.<br><br>CONCLUSION: There were no differences in the number of relapses between the study groups at the 12-mo follow-up. Thus, our results do not support the use of a single-dose FMT for the maintenance of remission in UC.}, }
@article {pmid37212669, year = {2023}, author = {Wu, Y and Dong, Z and Jiang, X and Qu, L and Zhou, W and Sun, X and Hou, J and Xu, H and Cheng, M}, title = {Gut Microbiota Taxon-Dependent Transformation of Microglial M1/M2 Phenotypes Underlying Mechanisms of Spatial Learning and Memory Impairment after Chronic Methamphetamine Exposure.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0030223}, pmid = {37212669}, issn = {2165-0497}, mesh = {Mice ; Animals ; *Methamphetamine/toxicity/metabolism ; Spatial Learning ; Microglia ; *Gastrointestinal Microbiome ; Memory Disorders/chemically induced/metabolism ; Phenotype ; }, abstract = {Methamphetamine (METH) exposure may lead to cognitive impairment. Currently, evidence suggests that METH exposure alters the configuration of the gut microbiota. However, the role and mechanism of the gut microbiota in cognitive impairment after METH exposure are still largely unknown. Here, we investigated the impact of the gut microbiota on the phenotype status of microglia (microglial phenotypes M1 and microglial M2) and their secreting factors, the subsequent hippocampal neural processes, and the resulting influence on spatial learning and memory of chronically METH-exposed mice. We determined that gut microbiota perturbation triggered the transformation of microglial M2 to M1 and a subsequent change of pro-brain-derived neurotrophic factor (proBDNF)-p75[NTR]-mature BDNF (mBDNF)-TrkB signaling, which caused reduction of hippocampal neurogenesis and synaptic plasticity-related proteins (SYN, PSD95, and MAP2) and, consequently, deteriorated spatial learning and memory. More specifically, we found that Clostridia, Bacteroides, Lactobacillus, and Muribaculaceae might dramatically affect the homeostasis of microglial M1/M2 phenotypes and eventually contribute to spatial learning and memory decline after chronic METH exposure. Finally, we found that fecal microbial transplantation could protect against spatial learning and memory decline by restoring the microglial M1/M2 phenotype status and the subsequent proBDNF-p75[NTR]/mBDNF-TrkB signaling in the hippocampi of chronically METH-exposed mice. IMPORTANCE Our study indicated that the gut microbiota contributes to spatial learning and memory dysfunction after chronic METH exposure, in which microglial phenotype status plays an intermediary role. The elucidated "specific microbiota taxa-microglial M1/M2 phenotypes-spatial learning and memory impairment" pathway would provide a novel mechanism and elucidate potential gut microbiota taxon targets for the no-drug treatment of cognitive deterioration after chronic METH exposure.}, }
@article {pmid37212529, year = {2023}, author = {Kvaerner, AS and Andersen, AR and Henriksen, HB and Knudsen, MD and Johansen, AMW and Hjartåker, A and Bøhn, SK and Paur, I and Wiedswang, G and Smeland, S and Rounge, TB and Blomhoff, R and Berstad, P}, title = {Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) cancer prevention recommendations with stages of colorectal carcinogenesis.}, journal = {Cancer medicine}, volume = {12}, number = {13}, pages = {14806-14819}, pmid = {37212529}, issn = {2045-7634}, mesh = {Humans ; United States/epidemiology ; *Patient Compliance ; Life Style ; Exercise ; Carcinogenesis ; *Colorectal Neoplasms/diagnosis/epidemiology/etiology ; Diet ; Risk Factors ; }, abstract = {BACKGROUND: While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with detection of colorectal lesions in a screening setting. As a secondary objective, we examined to what extent the recommendations were being followed in an external cohort of CRC patients.<br><br>METHODS: Adherence to the seven-point 2018 WCRF/AICR Score was measured in screening participants receiving a positive fecal immunochemical test and in CRC patients participating in an intervention study. Dietary intake, body fatness and physical activity were assessed using self-administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen-detected lesions.<br><br>RESULTS: Of 1486 screening participants, 548 were free from adenomas, 524 had non-advanced adenomas, 349 had advanced lesions and 65 had CRC. Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced lesions; OR 0.82 (95% CI 0.71, 0.94) per score point, but not with CRC. Of the seven individual components included in the score, alcohol, and BMI seemed to be the most influential. Of the 430 CRC patients included in the external cohort, the greatest potential for lifestyle improvement was seen for the recommendations concerning alcohol and red and processed meat, where 10% and 2% fully adhered, respectively.<br><br>CONCLUSIONS: Adherence to the 2018 WCRF/AICR Score was associated with lower probability of screen-detected advanced precancerous lesions, but not CRC. Although some components of the score seemed to be more influential than others (i.e., alcohol and BMI), taking a holistic approach to cancer prevention is likely the best way to prevent the occurrence of precancerous colorectal lesions.}, }
@article {pmid37211643, year = {2023}, author = {Rodig, NM and Weatherly, M and Kaplan, AL and Ballal, SA and Elisofon, SA and Daly, KP and Kahn, SA}, title = {Fecal Microbiota Transplant in Pediatric Solid Organ Transplant Recipients.}, journal = {Transplantation}, volume = {107}, number = {9}, pages = {2073-2077}, doi = {10.1097/TP.0000000000004656}, pmid = {37211643}, issn = {1534-6080}, support = {R24 AI118629/AI/NIAID NIH HHS/United States ; }, mesh = {Male ; Adult ; Humans ; Child ; Fecal Microbiota Transplantation/adverse effects ; Retrospective Studies ; *Clostridioides difficile ; Treatment Outcome ; *Clostridium Infections/epidemiology ; Transplant Recipients ; *Organ Transplantation/adverse effects ; }, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI). Safety concerns around FMT are increased in immunocompromised populations, such as solid organ transplant (SOT) recipients. Outcomes among adult SOT recipients suggest FMT is efficacious and safe; however, pediatric SOT data are lacking.<br><br>METHODS: We describe the efficacy and safety of FMT among pediatric SOT recipients in a single-center retrospective study from March 2016 to December 2019. Successful FMT was defined as no recurrence of CDI within 2 mo of FMT. We identified 6 SOT recipients ages 4-18 y who received FMT a median of 5.3 y post-SOT.<br><br>RESULTS: Success after a single FMT was 83.3%. One liver recipient did not achieve cure after 3 FMTs and remains on low-dose vancomycin. One serious adverse event (SAE) occurred; cecal perforation and bacterial peritonitis occurred following colonoscopic FMT coordinated with intestinal biopsy in a kidney transplant recipient. He achieved full recovery and CDI cure. There were no other SAEs. There were no adverse events related to immunosuppression or transplantation status including: bacteremia, cytomegalovirus activation or reactivation, allograft rejection, or allograft loss.<br><br>CONCLUSIONS: In this limited series, efficacy of FMT in pediatric SOT is comparable to efficacy in the general pediatric recurrent CDI population. There may be an increased risk of procedure-related SAE in SOT patients and larger cohort studies are needed.}, }
@article {pmid37211239, year = {2023}, author = {Varesi, A and Campagnoli, LIM and Chirumbolo, S and Candiano, B and Carrara, A and Ricevuti, G and Esposito, C and Pascale, A}, title = {The brain-gut-microbiota interplay in depression: A key to design innovative therapeutic approaches.}, journal = {Pharmacological research}, volume = {192}, number = {}, pages = {106799}, doi = {10.1016/j.phrs.2023.106799}, pmid = {37211239}, issn = {1096-1186}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Depression/therapy ; Brain ; *Probiotics/therapeutic use ; *Microbiota ; }, abstract = {Depression is the most prevalent mental disorder in the world associated with huge socio-economic consequences. While depressive-related symptoms are well known, the molecular mechanisms underlying disease pathophysiology and progression remain largely unknown. The gut microbiota (GM) is emerging as a key regulator of the central nervous system homeostasis by exerting fundamental immune and metabolic functions. In turn, the brain influences the intestinal microbial composition through neuroendocrine signals, within the so-called gut microbiota-brain axis. The balance of this bidirectional crosstalk is important to ensure neurogenesis, preserve the integrity of the blood-brain barrier and avoid neuroinflammation. Conversely, dysbiosis and gut permeability negatively affect brain development, behavior, and cognition. Furthermore, although not fully defined yet, changes in the GM composition in depressed patients are reported to influence the pharmacokinetics of common antidepressants by affecting their absorption, metabolism, and activity. Similarly, neuropsychiatric drugs may shape in turn the GM with an impact on the efficacy and toxicity of the pharmacological intervention itself. Consequently, strategies aimed at re-establishing the correct homeostatic gut balance (i.e., prebiotics, probiotics, fecal microbiota transplantation, and dietary interventions) represent an innovative approach to improve the pharmacotherapy of depression. Among these, probiotics and the Mediterranean diet, alone or in combination with the standard of care, hold promise for clinical application. Therefore, the disclosure of the intricate network between GM and depression will give precious insights for innovative diagnostic and therapeutic approaches towards depression, with profound implications for drug development and clinical practice.}, }
@article {pmid37211107, year = {2023}, author = {Hong, T and Zou, J and He, Y and Zhang, H and Liu, H and Mai, H and Yang, J and Cao, Z and Chen, X and Yao, J and Feng, D}, title = {Bisphenol A induced hepatic steatosis by disturbing bile acid metabolism and FXR/TGR5 signaling pathways via remodeling the gut microbiota in CD-1 mice.}, journal = {The Science of the total environment}, volume = {889}, number = {}, pages = {164307}, doi = {10.1016/j.scitotenv.2023.164307}, pmid = {37211107}, issn = {1879-1026}, mesh = {Male ; Mice ; Animals ; *Non-alcoholic Fatty Liver Disease/chemically induced ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Bile Acids and Salts ; Signal Transduction ; }, abstract = {Dysregulation of gut microbiota-mediated bile acid (BA) metabolism plays an important role in the pathogenesis of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Our previous studies found that bisphenol A (BPA) exposure induced hepatic steatosis and gut microbiota dysbiosis. However, whether the gut microbiota-dependent BA metabolism alterations were involved in BPA-induced hepatic steatosis remains unclear. Therefore, we explored the gut microbiota-related metabolic mechanisms of hepatic steatosis induced by BPA. Male CD-1 mice were exposed to low-dose BPA (50 μg/kg/day) for 6 months. Fecal microbiota transplantation (FMT) and broad-spectrum antibiotic cocktail (ABX) treatment were further adopted to test the role of gut microbiota in the adverse effects of BPA. We found that BPA induced hepatic steatosis in mice. Additionally, 16S rRNA gene sequencing showed that BPA reduced the relative abundance of Bacteroides, Parabacteroides and Akkermansia, which are associated with BA metabolism. Metabolomic analyses demonstrated that BPA significantly altered the ratio of conjugated to unconjugated BAs and increased the total level of taurine-α/β-muricholic acid while decreasing the level of chenodeoxycholic acid, thus inhibiting the activation of special receptors, including farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), in the ileum and liver. The inhibition of FXR reduced short heterodimer partner and subsequently induced cholesterol 7α-hydroxylase and sterol regulatory element-binding protein-1c expression, which is related to hepatic BA synthesis and lipogenesis, eventually leading to liver cholestasis and steatosis. Furthermore, we found that mice that received FMT from BPA-exposed mice developed hepatic steatosis, and the influences of BPA on hepatic steatosis and FXR/TGR5 signaling pathways could be eliminated by ABX treatment, confirming the role of gut microbiota in BPA effects. Collectively, our study illustrates that suppressed microbiota-BA-FXR/TGR signaling pathways may be a potential mechanism for hepatic steatosis induced by BPA, providing a new target for the prevention of BPA-induced NAFLD.}, }
@article {pmid37210914, year = {2023}, author = {Chen, Y and Shu, A and Jiang, M and Jiang, J and Du, Q and Chen, T and Shaw, C and Chai, W and Chao, T and Li, X and Wu, Q and Gao, C}, title = {Exenatide improves hypogonadism and attenuates inflammation in diabetic mice by modulating gut microbiota.}, journal = {International immunopharmacology}, volume = {120}, number = {}, pages = {110339}, doi = {10.1016/j.intimp.2023.110339}, pmid = {37210914}, issn = {1878-1705}, mesh = {Mice ; Male ; Animals ; Exenatide/therapeutic use/pharmacology ; Interleukin-6 ; Tumor Necrosis Factor-alpha/pharmacology ; *Diabetes Mellitus, Experimental/drug therapy ; NF-kappa B ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Inflammation ; *Hypogonadism/drug therapy ; }, abstract = {With the rising incidence of diabetes and its onset at a younger age, the impact on the male reproductive system has gradually gained attention. Exenatide is a glucagon-like peptide-1 receptor agonist effective in the treatment of diabetes. However, its role in diabetes-induced reproductive complications has rarely been reported. The study aimed to investigate the mechanism by which exenatide improved diabetic hypogonadism by regulating gut microbiota (GM) mediated inflammation. C57BL/6J mice were equally divided into normal control (NC), diabetic model control (DM) and exenatide-treated (Exe) groups. Testicular, pancreatic, colonic, and fecal samples were collected to assess microbiota, morphologic damage, and inflammation. Exenatide significantly reduced the fasting blood glucose (FBG) level in diabetic mice, increased the testosterone level, ameliorated the pathological morphological damage of islet, colon, and testes, and reduced the expression of pro-inflammatory factors, tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 in colon and testis. Furthermore, exenatide significantly reduced the abundance of some pathogenic bacteria, such as Streptococcaceae and Erysipelotrichaceae, and increased that of beneficial bacteria Akkermansia. Probiotics, such as Lactobacillus were negatively correlated with TNF-α, nuclear factor-kappa-B (NF-κB), IL-6, and FBG. Conditional pathogenic bacteria such as Escherichia/Shigella Streptococcus were positively correlated with TNF-α, NF-κB, IL-6, and FBG. The fecal bacteria transplantation experiment revealed that the abundance of pathogenic bacteria, Peptostreptococcaceae, significantly decreased from Exe group mice to pseudo-sterile diabetic mice, and the pathological damage to testes was also alleviated. These data suggested the protective effects of exenatide on male reproductive damage induced by diabetes by regulating GM.}, }
@article {pmid37208728, year = {2023}, author = {Yu, J and Meng, J and Qin, Z and Yu, Y and Liang, Y and Wang, Y and Min, D}, title = {Dysbiosis of gut microbiota inhibits NMNAT2 to promote neurobehavioral deficits and oxidative stress response in the 6-OHDA-lesioned rat model of Parkinson's disease.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {117}, pmid = {37208728}, issn = {1742-2094}, support = {NO. 2020-274//Scientific Research Project of Heilongjiang Provincial Health Commission/ ; GXZYB20220437//Project of Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine/ ; }, mesh = {Animals ; Rats ; Dysbiosis/metabolism ; *Gastrointestinal Microbiome/physiology ; NAD ; Oxidative Stress ; Oxidopamine/toxicity ; *Parkinson Disease/metabolism ; *Nicotinamide-Nucleotide Adenylyltransferase/metabolism ; }, abstract = {BACKGROUND: New data are accumulating on gut microbial dysbiosis in Parkinson's disease (PD), while the specific mechanism remains uncharacterized. This study aims to investigate the potential role and pathophysiological mechanism of dysbiosis of gut microbiota in 6-hydroxydopamine (6-OHDA)-induced PD rat models.<br><br>METHODS: The shotgun metagenome sequencing data of fecal samples from PD patients and healthy individuals were obtained from the Sequence Read Archive (SRA) database. The diversity, abundance, and functional composition of gut microbiota were further analyzed in these data. After the exploration of the functional pathway-related genes, KEGG and GEO databases were used to obtain PD-related microarray datasets for differential expression analysis. Finally, in vivo experiments were performed to confirm the roles of fecal microbiota transplantation (FMT) and upregulated NMNAT2 in neurobehavioral symptoms and oxidative stress response in 6-OHDA-lesioned rats.<br><br>RESULTS: Significant differences were found in the diversity, abundance, and functional composition of gut microbiota between PD patients and healthy individuals. Dysbiosis of gut microbiota could regulate NAD[+] anabolic pathway to affect the occurrence and development of PD. As a NAD[+] anabolic pathway-related gene, NMNAT2 was poorly expressed in the brain tissues of PD patients. More importantly, FMT or overexpression of NMNAT2 alleviated neurobehavioral deficits and reduced oxidative stress in 6-OHDA-lesioned rats.<br><br>CONCLUSIONS: Taken together, we demonstrated that dysbiosis of gut microbiota suppressed NMNAT2 expression, thus exacerbating neurobehavioral deficits and oxidative stress response in 6-OHDA-lesioned rats, which could be rescued by FMT or NMNAT2 restoration.}, }
@article {pmid37208544, year = {2023}, author = {Lange, O and Proczko-Stepaniak, M and Mika, A}, title = {Short-Chain Fatty Acids-A Product of the Microbiome and Its Participation in Two-Way Communication on the Microbiome-Host Mammal Line.}, journal = {Current obesity reports}, volume = {12}, number = {2}, pages = {108-126}, pmid = {37208544}, issn = {2162-4968}, support = {2021/43/B/NZ5/00039//Narodowe Centrum Nauki/ ; ST-40//Gda&#x144;ski Uniwersytet Medyczny/ ; }, mesh = {Animals ; Humans ; Obesity/metabolism ; *Microbiota ; *Gastrointestinal Microbiome ; Bacteria/metabolism ; Mammals/metabolism ; Fatty Acids, Volatile/metabolism/pharmacology/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: The review aims to describe short-chain fatty acids (SCFAs) as metabolites of bacteria, their complex influence on whole-body metabolism, and alterations in the SCFA profile in obesity and after bariatric surgery (BS).<br><br>RECENT FINDINGS: The fecal profile of SCFAs in obese patients differs from that of lean patients, as well as their gut microbiota composition. In obese patients, a lower diversity of bacteria is observed, as well as higher concentrations of SCFAs in stool samples. Obesity is now considered a global epidemic and bariatric surgery (BS) is an effective treatment for severe obesity. BS affects the structure and functioning of the digestive system, and also alters gut microbiota and the concentration of fecal SCFAs. Generally, after BS, SCFA levels are lower but levels of branched short-chain fatty acids (BSCFAs) are elevated, the effect of which is not fully understood. Moreover, changes in the profile of circulating SCFAs are little known and this is an area for further research. Obesity seems to be inherently associated with changes in the SCFA profile. It is necessary to better understand the impact of BS on microbiota and the metabolome in both feces and blood as only a small percentage of SCFAs are excreted. Further research may allow the development of a personalized therapeutic approach to the BS patient in terms of diet and prebiotic intervention.}, }
@article {pmid37207204, year = {2023}, author = {Hamada, K and Isobe, J and Hattori, K and Hosonuma, M and Baba, Y and Murayama, M and Narikawa, Y and Toyoda, H and Funayama, E and Tajima, K and Shida, M and Hirasawa, Y and Tsurui, T and Ariizumi, H and Ishiguro, T and Suzuki, R and Ohkuma, R and Kubota, Y and Sambe, T and Tsuji, M and Wada, S and Kiuchi, Y and Kobayashi, S and Kuramasu, A and Horiike, A and Kim, YG and Tsunoda, T and Yoshimura, K}, title = {Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1164724}, pmid = {37207204}, issn = {1664-3224}, mesh = {Humans ; *Immune Checkpoint Inhibitors/adverse effects ; Acidaminococcus ; *Neoplasms/drug therapy/etiology ; Immunotherapy/adverse effects ; Tumor Microenvironment ; }, abstract = {INTRODUCTION: Immune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown.<br><br>METHODS: We investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).<br><br>RESULTS: The genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.<br><br>DISCUSSION: Our Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy.}, }
@article {pmid37205307, year = {2023}, author = {Kouidhi, S and Zidi, O and Belkhiria, Z and Rais, H and Ayadi, A and Ben Ayed, F and Mosbah, A and Cherif, A and El Gaaied, ABA}, title = {Gut microbiota, an emergent target to shape the efficiency of cancer therapy.}, journal = {Exploration of targeted anti-tumor therapy}, volume = {4}, number = {2}, pages = {240-265}, pmid = {37205307}, issn = {2692-3114}, abstract = {It is now well-acknowledged that microbiota has a profound influence on both human health and illness. The gut microbiota has recently come to light as a crucial element that influences cancer through a variety of mechanisms. The connections between the microbiome and cancer therapy are further highlighted by a number of preclinical and clinical evidence, suggesting that these complicated interactions may vary by cancer type, treatment, or even by tumor stage. The paradoxical relationship between gut microbiota and cancer therapies is that in some cancers, the gut microbiota may be necessary to maintain therapeutic efficacy, whereas, in other cancers, gut microbiota depletion significantly increases efficacy. Actually, mounting research has shown that the gut microbiota plays a crucial role in regulating the host immune response and boosting the efficacy of anticancer medications like chemotherapy and immunotherapy. Therefore, gut microbiota modulation, which aims to restore gut microbial balance, is a viable technique for cancer prevention and therapy given the expanding understanding of how the gut microbiome regulates treatment response and contributes to carcinogenesis. This review will provide an outline of the gut microbiota's role in health and disease, along with a summary of the most recent research on how it may influence the effectiveness of various anticancer medicines and affect the growth of cancer. This study will next cover the newly developed microbiota-targeting strategies including prebiotics, probiotics, and fecal microbiota transplantation (FMT) to enhance anticancer therapy effectiveness, given its significance.}, }
@article {pmid37205106, year = {2023}, author = {Wang, M and Zhang, Y and Li, C and Chang, W and Zhang, L}, title = {The relationship between gut microbiota and COVID-19 progression: new insights into immunopathogenesis and treatment.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1180336}, pmid = {37205106}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/therapy ; SARS-CoV-2 ; *Gastrointestinal Microbiome ; COVID-19 Drug Treatment ; Gastrointestinal Tract ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a global health crisis. Increasing evidence underlines the key role of competent immune responses in resisting SARS-CoV-2 infection and manifests the disastrous consequence of host immune dysregulation. Elucidating the mechanisms responsible for deregulated host immunity in COVID-19 may provide a theoretical basis for further research on new treatment modalities. Gut microbiota comprises trillions of microorganisms colonizing the human gastrointestinal tract and has a vital role in immune homeostasis and the gut-lung crosstalk. Particularly, SARS-CoV-2 infection can lead to the disruption of gut microbiota equilibrium, a condition called gut dysbiosis. Due to its regulatory effect on host immunity, gut microbiota has recently received considerable attention in the field of SARS-CoV-2 immunopathology. Imbalanced gut microbiota can fuel COVID-19 progression through production of bioactive metabolites, intestinal metabolism, enhancement of the cytokine storm, exaggeration of inflammation, regulation of adaptive immunity and other aspects. In this review, we provide an overview of the alterations in gut microbiota in COVID-19 patients, and their effects on individuals' susceptibility to viral infection and COVID-19 progression. Moreover, we summarize currently available data on the critical role of the bidirectional regulation between intestinal microbes and host immunity in SARS-CoV-2-induced pathology, and highlight the immunomodulatory mechanisms of gut microbiota contributing to COVID-19 pathogenesis. In addition, we discuss the therapeutic benefits and future perspectives of microbiota-targeted interventions including faecal microbiota transplantation (FMT), bacteriotherapy and traditional Chinese medicine (TCM) in COVID-19 treatment.}, }
@article {pmid37204182, year = {2024}, author = {Wu, X and Tian, X and Cao, G and Wang, Z and Wu, X and Gu, Y and Yan, T}, title = {Distinct profiles of bile acid metabolism caused by gut microbiota in kidney transplantation recipients revealed by 16S rRNA gene sequencing.}, journal = {Archives of physiology and biochemistry}, volume = {130}, number = {5}, pages = {581-590}, doi = {10.1080/13813455.2023.2212331}, pmid = {37204182}, issn = {1744-4160}, mesh = {*Kidney Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; *Bile Acids and Salts/metabolism ; *RNA, Ribosomal, 16S/genetics ; Male ; Female ; Adult ; Middle Aged ; Phylogeny ; Feces/microbiology ; }, abstract = {The present study sought to characterise the gut microbiota of subjects with kidney transplantation and healthy control to identify the distinct gut microbiota and analyse their potential function. We found that gut microbiota abundance had significant differences in subjects between the two groups. Line Discriminant Analysis (LDA) Effect Size (LEfSe) analysis showed that the bacterial taxa were differentially represented between the two groups, and the potential biomarkers at different taxonomic levels in kidney transplant recipients were Streptococcus, Enterococcaceae, and Ruminococcus. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) Functional Inference analyses suggested that the difference in gut microbiota between the two groups was correlated with bile acid metabolism. In conclusion, gut microbiota abundance is different between the two groups, which is related to bile acid metabolism, and may influence the metabolic homeostasis of allograft recipients.}, }
@article {pmid37204063, year = {2023}, author = {Zhao, X and Zhang, T and Zheng, Y and Zhao, Z and Ding, W and Zhang, Z and Zhang, Z and Wang, R and Jiao, M and Liu, L and Yu, S and Wang, X and Huang, R and Wu, Q}, title = {Gut Microbiota from Short-Chain Chlorinated Paraffin-Exposed Mice Promotes Astrocyte Activation by Disrupting the Intestinal Tight Junction via Zonulin Upregulation.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {21}, pages = {8192-8202}, doi = {10.1021/acs.jafc.3c01058}, pmid = {37204063}, issn = {1520-5118}, mesh = {Animals ; Mice ; Paraffin ; *Gastrointestinal Microbiome ; Up-Regulation ; Astrocytes ; Tight Junctions ; Environmental Monitoring ; *Hydrocarbons, Chlorinated ; China ; }, abstract = {Short-chain chlorinated paraffins (SCCPs) are novel toxicants in food and are reported to possess neurotoxicity. Here, we investigated the mechanism of SCCP-induced astrocyte activation and neuroinflammation. SCCP gavage induced astrocyte activation and neuronal cell death with the changes of gut microbiome and metabolites. Antibiotic cocktail administration to deplete the gut microbiome ameliorated the astrocyte activation and inflammation induced by SCCPs. In fecal microbiota transplantation (FMT) assays, mice that received transplanted gut microbiome from SCCP-treated mice showed increased astrocyte activation and elevated inflammatory response. In addition, SCCP exposure promotes zonulin expression and tight junction injury, and antibiotic cocktail administration inhibited that in the intestinal tract. Increased zonulin and tight junction injury were also observed in SCCPs_FMT mice. The zonulin inhibition protected the tight junction in the intestinal tract from SCCP exposure and suppressed astrocyte activation. In summary, this study proposes a novel possibility for SCCP-induced astrocyte activation and neurotoxicity by the gut microbiome-mediated zonulin expression and tight junction.}, }
@article {pmid37203380, year = {2023}, author = {Zhou, W and Liu, P and Xu, W and Ran, L and Yan, Y and Lu, L and Zeng, X and Cao, Y and Mi, J}, title = {A purified fraction of polysaccharides from the fruits of Lycium barbarum L. improves glucose homeostasis and intestinal barrier function in high-fat diet-fed mice.}, journal = {Food &amp; function}, volume = {14}, number = {11}, pages = {5311-5325}, doi = {10.1039/d3fo00262d}, pmid = {37203380}, issn = {2042-650X}, mesh = {Mice ; Animals ; *Lycium ; Diet, High-Fat/adverse effects ; Fruit ; Polysaccharides/pharmacology ; Homeostasis ; Glucose ; Mice, Inbred C57BL ; }, abstract = {High-fat diet (HFD) consumption can induce intestinal barrier dysfunction and disrupt glucose metabolism. Our previous studies have demonstrated that polysaccharides obtained from the fruits of Lycium barbarum L. (LBPs) could suppress acute experimental diabetes as well as colitis in mice. In the present study, the modulating effects of a purified fraction of LBPs, named LBPs-4, on glucose homeostasis and intestinal barrier function in mice fed with a HFD were investigated. Our results indicated that the oral administration of LBP-4 (200 mg per kg per day) improved hyperglycemia, glucose intolerance, insulin resistance and islet β-cell hyperplasia in HFD-fed mice. Moreover, LBPs-4 intervention enhanced the intestinal barrier integrity by increasing the expression levels of zonula occludens 1 and claudin-1 and the number of goblet cells in the colon. LBPs-4 also modulated the composition of gut microbiota by increasing the relative abundances of butyrate producer Allobaculum and acetate producer Romboutsia. The results of fecal transplantation experiments, transferring of microbiota from LBPs-4-fed donor mice to HFD-fed recipient mice, validated the cause-effect relationship between LBPs-4-evoked changes in the gut microbiota and improvement of glucose homeostasis and intestinal barrier function. Collectively, these findings suggested that LBPs-4 might be developed as promising prebiotics to improve glucose metabolism and gut health.}, }
@article {pmid37202543, year = {2024}, author = {Zeng, N and Wu, F and Lu, J and Li, X and Lin, S and Zhou, L and Wang, Z and Wu, G and Huang, Q and Zheng, D and Gao, J and Wu, S and Chen, X and Chen, M and Meng, F and Shang, H and He, Y and Chen, P and Wei, H and Li, Z and Zhou, H}, title = {High-fat diet impairs gut barrier through intestinal microbiota-derived reactive oxygen species.}, journal = {Science China. Life sciences}, volume = {67}, number = {5}, pages = {879-891}, pmid = {37202543}, issn = {1869-1889}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Diet, High-Fat/adverse effects ; *Reactive Oxygen Species/metabolism ; Mice ; *Fecal Microbiota Transplantation ; *Mice, Inbred C57BL ; Male ; Intestinal Mucosa/metabolism/microbiology ; Dysbiosis/microbiology ; Superoxide Dismutase/metabolism ; Feces/microbiology ; Tight Junctions/metabolism ; }, abstract = {Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet (HFD)-associated metabolic disorders. However, the underlying mechanism remains elusive. In the present study, by comparing HFD- and normal diet (ND)-treated mice, we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut barrier. Metagenomic sequencing revealed that the HFD upregulates gut microbial functions related to redox reactions, as confirmed by the increased reactive oxygen species (ROS) levels in fecal microbiota incubation in vitro and in the lumen, which were detected using in vivo fluorescence imaging. This microbial ROS-producing capability induced by HFD can be transferred through fecal microbiota transplantation (FMT) into germ-free (GF) mice, downregulating the gut barrier tight junctions. Similarly, mono-colonizing GF mice with an Enterococcus strain excelled in ROS production, damaged the gut barrier, induced mitochondrial malfunction and apoptosis of the intestinal epithelial cells, and exacerbated fatty liver, compared with other low-ROS-producing Enterococcus strains. Oral administration of recombinant high-stability-superoxide dismutase (SOD) significantly reduced intestinal ROS, protected the gut barrier, and improved fatty liver against the HFD. In conclusion, our study suggests that extracellular ROS derived from gut microbiota play a pivotal role in HFD-induced gut barrier disruption and is a potential therapeutic target for HFD-associated metabolic diseases.}, }
@article {pmid37201335, year = {2023}, author = {Laragione, T and Harris, C and Azizgolshani, N and Beeton, C and Bongers, G and Gulko, PS}, title = {Magnesium increases numbers of Foxp3+ Treg cells and reduces arthritis severity and joint damage in an IL-10-dependent manner mediated by the intestinal microbiome.}, journal = {EBioMedicine}, volume = {92}, number = {}, pages = {104603}, pmid = {37201335}, issn = {2352-3964}, support = {R01 AR073165/AR/NIAMS NIH HHS/United States ; }, mesh = {Mice ; Animals ; T-Lymphocytes, Regulatory ; Magnesium/metabolism/pharmacology ; Interleukin-10/genetics/metabolism ; *Gastrointestinal Microbiome ; Cytokines/metabolism ; *Arthritis, Rheumatoid/metabolism ; Mice, Knockout ; Th17 Cells ; Forkhead Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with emerging environmental and microbiome risk factors. The western diet is typically deficient in magnesium (Mg), and there is some evidence suggesting that Mg may have anti-inflammatory properties. But the actual role of Mg supplementation in arthritis or in T cell subsets has not been explored.<br><br>METHODS: We investigated the role of a high Mg diet in two different mouse models of RA induced with the KRN serum, and collagen-induced arthritis. We also characterized the phenotypes of splenocytes, gene expression, and an extensive intestinal microbiome analyses including fecal material transplantation (FMT).<br><br>FINDINGS: The high Mg diet group was significantly protected with reduced arthritis severity and joint damage, and reduced expression of IL-1&#x3b2;, IL-6, and TNF&#x3b1;. The high Mg group also had increased numbers of Foxp3+ Treg cells and IL-10-producing T cells. The high Mg protective effect disappeared in IL-10 knockout mice. FMT from the high Mg diet mice recreated the phenotypes seen in the diet-treated mice, with reduced arthritis severity, increased Foxp3+ Treg, and increased IL-10-producing T cells. Intestinal microbiome analyses using 16S rDNA sequencing revealed diet-specific changes, including reduced levels of RA-associated Prevotella in the high Mg group, while increasing levels of Bacteroides and other bacteria associated with increased production of short-chain fatty acids. Metagenomic analyses implicated additional pathways including L-tryptophan biosynthesis and arginine deiminase.<br><br>INTERPRETATION: We describe a new role for Mg in suppressing arthritis, in expanding Foxp3+ T reg cells and in the production of IL-10, and show that these effects are mediated by the intestinal microbiome. Our discoveries suggest a novel strategy for modifying the intestinal microbiome to treat RA and other autoimmune and inflammatory diseases.<br><br>FUNDING: None.}, }
@article {pmid37200942, year = {2023}, author = {Jiang, Z and Wang, X and Zhang, H and Yin, J and Zhao, P and Yin, Q and Wang, Z}, title = {Ketogenic diet protects MPTP-induced mouse model of Parkinson's disease via altering gut microbiota and metabolites.}, journal = {MedComm}, volume = {4}, number = {3}, pages = {e268}, pmid = {37200942}, issn = {2688-2663}, abstract = {The ketogenic diet (KD) is a low-carbohydrate, high-fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP-induced histamine, N-acetylputrescine, d-aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD-treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic-pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet-gut microbiota-brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti-inflammatory mechanisms of the gut-brain axis in PD models fed with KD.}, }
@article {pmid37200041, year = {2023}, author = {Zhang, B and Li, J and Fu, J and Shao, L and Yang, L and Shi, J}, title = {Interaction between mucus layer and gut microbiota in non-alcoholic fatty liver disease: Soil and seeds.}, journal = {Chinese medical journal}, volume = {136}, number = {12}, pages = {1390-1400}, pmid = {37200041}, issn = {2542-5641}, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/therapy ; *Gastrointestinal Microbiome ; *Probiotics ; Prebiotics ; Fecal Microbiota Transplantation ; Bacteria ; Liver/pathology ; }, abstract = {The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells, as well as acts as the "mucus layer-soil" for intestinal flora adhesion and colonization. Its structural and functional integrity is crucial to human health. Intestinal mucus is regulated by factors such as diet, living habits, hormones, neurotransmitters, cytokines, and intestinal flora. The mucus layer's thickness, viscosity, porosity, growth rate, and glycosylation status affect the structure of the gut flora colonized on it. The interaction between "mucus layer-soil" and "gut bacteria-seed" is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Probiotics, prebiotics, fecal microbiota transplantation (FMT), and wash microbial transplantation are efficient methods for managing NAFLD, but their long-term efficacy is poor. FMT is focused on achieving the goal of treating diseases by enhancing the "gut bacteria-seed". However, a lack of effective repair and management of the "mucus layer-soil" may be a reason why "seeds" cannot be well colonized and grow in the host gut, as the thinning and destruction of the "mucus layer-soil" is an early symptom of NAFLD. This review summarizes the existing correlation between intestinal mucus and gut microbiota, as well as the pathogenesis of NAFLD, and proposes a new perspective that "mucus layer-soil" restoration combined with "gut bacteria-seed" FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.}, }
@article {pmid37199714, year = {2023}, author = {Bai, Y and Meng, Q and Wang, C and Ma, K and Li, J and Li, J and Shan, A}, title = {Gut Microbiota Mediates Lactobacillus rhamnosus GG Alleviation of Deoxynivalenol-Induced Anorexia.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {21}, pages = {8164-8181}, doi = {10.1021/acs.jafc.2c08076}, pmid = {37199714}, issn = {1520-5118}, mesh = {Male ; Animals ; Mice ; Mice, Inbred BALB C ; *Anorexia/chemically induced/microbiology ; *Gastrointestinal Microbiome ; *Lactobacillus/drug effects ; Anti-Bacterial Agents/pharmacology ; Cecum/drug effects/microbiology ; Enterocolitis/microbiology ; }, abstract = {Deoxynivalenol (DON) is a widespread mycotoxin and causes anorexia and emesis in humans and animals; Lactobacillus rhamnosus GG (LGG), a well-characterized probiotic, can improve intestinal barrier function and modulate immune response. Currently, it is unclear whether LGG has a beneficial effect on DON-induced anorexia. In the present study, mice were treated with DON, LGG, or both by gavage for 28 days to evaluate the effects of LGG on DON-induced anorexia. Antibiotic treatment and fecal microbiota transplant (FMT) experiment were also conducted to investigate the link between DON, LGG, and gut microbiota. LGG significantly increased the villus height and reduced the crypt depth in jejunum and ileum, enhanced the tight junction proteins expression in the intestine, and regulated the TLR4/NF-κB signaling pathway, consequently attenuating the intestinal inflammation caused by DON. In addition, LGG increased the relative abundance of Lactobacillus and butyric acid production of cecal contents; remodeled phenylalanine metabolism and tryptophan metabolism; reduced plasma peptide tyrosine tyrosine (PYY), 5-hydroxytryptamine (5-HT), and glucagon-like peptide-1 (GLP-1) concentrations; and promoted hypothalamic NPY and AgPR gene expression, which will further promote food intake and reduce weight loss, ultimately alleviating DON-induced anorexia in mice. Interestingly, antibiotic treatment diminished the intestinal toxicity of DON. The FMT experiment showed that DON-originated microbiota promotes intestinal inflammation and anorexia, while LGG + DON-originated microbiota has no adverse effects on mice. Both antibiotic treatment and FMT experiment have proved that gut microbiota was the primary vector for DON to exert its toxic effects and an essential mediator of LGG protection. In summary, our findings demonstrate that gut microbiota plays essential roles in DON-induced anorexia, and LGG can reduce the adverse effects caused by DON through its structure and regulate the gut microbiota, which may lay the important scientific foundation for future applications of LGG in food and feed products.}, }
@article {pmid37199635, year = {2023}, author = {Tao, Z and Chen, Y and He, F and Tang, J and Zhan, L and Hu, H and Ding, Z and Ruan, S and Chen, Y and Chen, B and Wang, Y and Guo, X and Xie, L and Zhong, M and Huang, Q}, title = {Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0007623}, pmid = {37199635}, issn = {2165-0497}, mesh = {Animals ; Female ; Humans ; Mice ; Pregnancy ; Dysbiosis ; *Fetal Growth Retardation/metabolism/microbiology ; *Gastrointestinal Microbiome ; Placenta/pathology ; Cohort Studies ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Bacteria/classification/genetics/metabolism ; Adult ; Biodiversity ; Serum/metabolism ; }, abstract = {Fetuses diagnosed with fetal growth restriction (FGR) are at an elevated risk of stillbirth and adulthood morbidity. Gut dysbiosis has emerged as one of the impacts of placental insufficiency, which is the main cause of FGR. This study aimed to characterize the relationships among the intestinal microbiome, metabolites, and FGR. Characterization was conducted on the gut microbiome, fecal metabolome, and human phenotypes in a cohort of 35 patients with FGR and 35 normal pregnancies (NP). The serum metabolome was analyzed in 19 patients with FGR and 31 normal pregnant women. Multidimensional data was integrated to reveal the links between data sets. A fecal microbiota transplantation mouse model was used to determine the effects of the intestinal microbiome on fetal growth and placental phenotypes. The diversity and composition of the gut microbiota were altered in patients with FGR. A group of microbial species altered in FGR closely correlated with fetal measurements and maternal clinical variables. Fecal and serum metabolism profiles were distinct in FGR patients compared to those in the NP group. Altered metabolites were identified and associated with clinical phenotypes. Integrated multi-omics analysis revealed the interactions among gut microbiota, metabolites, and clinical measurements. Microbiota from FGR gravida transplanted to mice progestationally induced FGR and placental dysfunction, including impaired spiral artery remodeling and insufficient trophoblast cell invasion. Taken together, the integration of microbiome and metabolite profiles from the human cohort indicates that patients with FGR endure gut dysbiosis and metabolic disorders, which contribute to disease pathogenesis. IMPORTANCE Downstream of the primary cause of fetal growth restriction are placental insufficiency and fetal malnutrition. Gut microbiota and metabolites appear to play an important role in the progression of gestation, while dysbiosis induces maternal and fetal complications. Our study elaborates the significant differences in microbiota profiles and metabolome characteristics between women with FGR and normal pregnancies. This is the first attempt so far that reveals the mechanistic links in multi-omics in FGR, providing a novel insight into host-microbe interaction in placenta-derived diseases.}, }
@article {pmid37199590, year = {2023}, author = {Xie, Z and Zhang, M and Luo, Y and Jin, D and Guo, X and Yang, W and Zheng, J and Zhang, H and Zhang, L and Deng, C and Zheng, W and Tan, EK and Jin, K and Zhu, S and Wang, Q}, title = {Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway.}, journal = {Aging and disease}, volume = {14}, number = {6}, pages = {2193-2214}, pmid = {37199590}, issn = {2152-5250}, abstract = {Increasing evidence has shown that gut dysbacteriosis may play a crucial role in neuroinflammation in Parkinson's disease (PD). However, the specific mechanisms that link gut microbiota to PD remain unexplored. Given the critical roles of blood-brain barrier (BBB) dysfunction and mitochondrial dysfunction in the development of PD, we aimed to evaluate the interactions among the gut microbiota, BBB, and mitochondrial resistance to oxidation and inflammation in PD. We investigated the effects of fecal microbiota transplantation (FMT) on the physiopathology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The aim was to explore the role of fecal microbiota from PD patients and healthy human controls in neuroinflammation, BBB components, and mitochondrial antioxidative capacity via the AMPK/SOD2 pathway. Compared to control mice, MPTP-treated mice exhibited elevated levels of Desulfovibrio, whereas mice given FMT from PD patients exhibited enriched levels of Akkermansia and mice given FMT from healthy humans showed no significant alterations in gut microbiota. Strikingly, FMT from PD patients to MPTP-treated mice significantly aggravated motor impairments, dopaminergic neurodegeneration, nigrostriatal glial activation and colonic inflammation, and inhibited the AMPK/SOD2 signaling pathway. However, FMT from healthy human controls greatly improved the aforementioned MPTP-caused effects. Surprisingly, the MPTP-treated mice displayed a significant loss in nigrostriatal pericytes, which was restored by FMT from healthy human controls. Our findings demonstrate that FMT from healthy human controls can correct gut dysbacteriosis and ameliorate neurodegeneration in the MPTP-induced PD mouse model by suppressing microgliosis and astrogliosis, ameliorating mitochondrial impairments via the AMPK/SOD2 pathway, and restoring the loss of nigrostriatal pericytes and BBB integrity. These findings raise the possibility that the alteration in the human gut microbiota may be a risk factor for PD and provide evidence for potential application of FMT in PD preclinical treatment.}, }
@article {pmid37198039, year = {2023}, author = {Emile, SH and Garoufalia, Z and Aeschbacher, P and Horesh, N and Gefen, R and Wexner, SD}, title = {Endorectal advancement flap compared to ligation of inter-sphincteric fistula tract in the treatment of complex anal fistulas: A meta-analysis of randomized clinical trials.}, journal = {Surgery}, volume = {174}, number = {2}, pages = {172-179}, doi = {10.1016/j.surg.2023.04.004}, pmid = {37198039}, issn = {1532-7361}, mesh = {Female ; Humans ; Male ; Anal Canal/surgery ; *Fecal Incontinence/epidemiology/etiology ; Inflammation/complications ; Ligation/adverse effects ; Neoplasm Recurrence, Local/complications ; Pain, Postoperative/epidemiology/etiology ; Randomized Controlled Trials as Topic ; *Rectal Fistula/surgery/etiology ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Rectal advancement flap and ligation of intersphincteric fistula tract are common procedures for treating complex anal fistula. The present meta-analysis aimed to compare the surgical outcomes of advancement flap and ligation of intersphincteric fistula tract.<br><br>METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of randomized clinical trials comparing the ligation of intersphincteric fistula tract and advancement flap was conducted. PubMed, Scopus, and Web of Science were searched through January 2023. The risk of bias was assessed using the Risk of Bias 2 tool and certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation approach. The primary outcomes were healing and recurrence of anal fistulas, and secondary outcomes were operative time, complications, fecal incontinence, and early pain.<br><br>RESULTS: Three randomized clinical trials (193 patients, 74.6% male) were included. The median follow-up was 19.2 months. Two trials had a low risk of bias, and 1 had some risk of bias. The odds of healing (odds ratio: 1.363, 95% confidence interval: 0.373-4.972, P&#xa0;= .639), recurrence (odds ratio: 0.525, 95% confidence interval: 0.263-1.047, P&#xa0;= .067), and complications (odds ratio: 0.356, 95% confidence interval: 0.085-1.487, P&#xa0;= .157) were similar between the 2 procedures. Ligation of intersphincteric fistula tract was associated with a significantly shorter operation time (weighted mean difference: -4.876, 95% confidence interval: -7.988 to -1.764, P&#xa0;= .002) and less postoperative pain (weighted mean difference: -1.030, 95% confidence interval: -1.418 to -0.641, 0.198, P < .001, I[2]&#xa0;= 3.85%) than advancement flap. Ligation of intersphincteric fistula tract was associated with marginally lower odds of fecal incontinence than advancement flap (odds ratio: 0.27, 95% confidence interval: 0.069-1.06, P&#xa0;= .06).<br><br>CONCLUSION: Ligation of intersphincteric fistula tract and advancement flap had similar odds of healing, recurrence, and complications. The odds of fecal incontinence and extent of pain after ligation of intersphincteric fistula tract were lower than after advancement flap.}, }
@article {pmid37197060, year = {2023}, author = {Yang, W and Xia, Z and Zhu, Y and Tang, H and Xu, H and Hu, X and Lin, C and Jiang, T and He, P and Shen, J}, title = {Comprehensive Study of Untargeted Metabolomics and 16S rRNA Reveals the Mechanism of Fecal Microbiota Transplantation in Improving a Mouse Model of T2D.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {16}, number = {}, pages = {1367-1381}, pmid = {37197060}, issn = {1178-7007}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a new therapy targeting gastrointestinal microbiota for the treatment of a growing number of diseases in recent years. Previous studies have suggested that FMT may be a potential therapy for type 2 diabetes (T2D), but the underlying mechanism remains unclear. Therefore, in the present study, we aimed to investigate the role of FMT in T2D and its underlying mechanisms.<br><br>METHODS: To induce T2D, mice were fed a high-fat diet and injected with low-dose streptozotocin (STZ) for four weeks. The mice were then randomly divided into four groups: control group (n = 7), T2D group (n = 7), metformin (MET)-treated group (n = 7), and FMT group (n = 7). The MET group was orally administered 0.2 g/kg MET, the FMT group was orally administered 0.3 mL of bacterial solution, and the other two groups were orally administered the same volume of saline for four weeks. Serum and fecal samples were collected for non-targeted metabolomics, biochemical indicators, and 16S rRNA sequencing, respectively.<br><br>RESULTS: Our results demonstrated that FMT had a curative effect on T2D by ameliorating hyperlipidemia and hyperglycemia. Using 16S rRNA sequencing and serum untargeted metabolomic analysis, we found that FMT could restore the disorders of gastrointestinal microbiota in T2D mice. Moreover, corticosterone, progesterone, L-urobilin, and other molecules were identified as biomarkers after FMT treatment. Our bioinformatics analysis suggested that steroid hormone biosynthesis, arginine, proline metabolism, and unsaturated fatty acid biosynthesis could be potential regulatory mechanisms of FMT.<br><br>CONCLUSION: In summary, our study provides comprehensive evidence for the role of FMT in the treatment of T2D. FMT has the potential to become a promising strategy for the treatment of metabolic disorders, T2D, and diabetes-related complications.}, }
@article {pmid37196685, year = {2023}, author = {Fang, C and Zuo, K and Liu, Z and Liu, Y and Liu, L and Wang, Y and Yin, X and Li, J and Liu, X and Chen, M and Yang, X}, title = {Disordered gut microbiota promotes atrial fibrillation by aggravated conduction disturbance and unbalanced linoleic acid/SIRT1 signaling.}, journal = {Biochemical pharmacology}, volume = {213}, number = {}, pages = {115599}, doi = {10.1016/j.bcp.2023.115599}, pmid = {37196685}, issn = {1873-2968}, mesh = {Animals ; Mice ; *Atrial Fibrillation/etiology/therapy ; *Gastrointestinal Microbiome/physiology ; Heart Atria ; Linoleic Acid ; Sirtuin 1/genetics ; }, abstract = {Emerging evidence suggests an association of dysbiotic gut microbiota (GM) with atrial fibrillation (AF). The current study aimed to determine whether aberrant GM promotes AF development. A fecal microbiota transplantation (FMT) mouse model demonstrated that dysbiotic GM is sufficient to enhance AF susceptibility assessed by transesophageal burst pacing. Compared with recipients transplanted with GM obtained from healthy subjects (FMT-CH), the prolonged P wave duration and an enlarging tendency for the left atrium were detected in recipients transplanted with AF GM (FMT-AF). Meanwhile, the disrupted localizations of connexin 43 and N-cadherin and increased expression levels of phospho-CaMKII and phospho-RyR2, were observed in the atrium of FMT-AF, which indicated aggravated electrical remodeling caused by the altered gut flora. Specifically, exacerbated fibrosis disarray, collagen deposition, α-SMA expression, and inflammation in the atrium were also confirmed to be transmissible by the GM. Furthermore, deteriorated intestinal epithelial barrier and intestinal permeability, accompanied by disturbing metabolomic features in both feces and plasma, especially decreased linoleic acid (LA), were identified in FMT-AF mice. Subsequently, the anti-inflammatory role of LA among the imbalanced SIRT1 signaling discovered in the atrium of FMT-AF was confirmed in mouse HL-1 cells treated with LPS/nigericin, LA, and SIRT1 knockdown. This study provides preliminary insights into the causal role of aberrant GM in the pathophysiology of AF, suggesting the GM-intestinal barrier-atrium axis might participate in the vulnerable substrates for AF development, and the GM could be utilized as an environmental target in AF management.}, }
@article {pmid37196633, year = {2023}, author = {Yadav, J and Liang, T and Qin, T and Nathan, N and Schwenger, KJP and Pickel, L and Xie, L and Lei, H and Winer, DA and Maughan, H and Robertson, SJ and Woo, M and Lou, W and Banks, K and Jackson, T and Okrainec, A and Hota, SS and Poutanen, SM and Sung, HK and Allard, JP and Philpott, DJ and Gaisano, HY}, title = {Gut microbiome modified by bariatric surgery improves insulin sensitivity and correlates with increased brown fat activity and energy expenditure.}, journal = {Cell reports. Medicine}, volume = {4}, number = {5}, pages = {101051}, pmid = {37196633}, issn = {2666-3791}, support = {TB2-138775//CIHR/Canada ; }, mesh = {Mice ; Animals ; *Insulin Resistance ; *Gastrointestinal Microbiome ; Adipose Tissue, Brown ; *Bariatric Surgery ; Obesity/surgery ; Energy Metabolism ; }, abstract = {Alterations in the microbiome correlate with improved metabolism in patients following bariatric surgery. While fecal microbiota transplantation (FMT) from obese patients into germ-free (GF) mice has suggested a significant role of the gut microbiome in metabolic improvements following bariatric surgery, causality remains to be confirmed. Here, we perform paired FMT from the same obese patients (BMI > 40; four patients), pre- and 1 or 6 months post-Roux-en-Y gastric bypass (RYGB) surgery, into Western diet-fed GF mice. Mice colonized by FMT from patients' post-surgery stool exhibit significant changes in microbiota composition and metabolomic profiles and, most importantly, improved insulin sensitivity compared with pre-RYGB FMT mice. Mechanistically, mice harboring the post-RYGB microbiome show increased brown fat mass and activity and exhibit increased energy expenditure. Moreover, improvements in immune homeostasis within the white adipose tissue are also observed. Altogether, these findings point to a direct role for the gut microbiome in mediating improved metabolic health post-RYGB surgery.}, }
@article {pmid37196556, year = {2023}, author = {Liu, H and Kang, X and Ren, P and Kuang, X and Yang, X and Yang, H and Shen, X and Yan, H and Kang, Y and Zhang, F and Wang, X and Guo, L and Fan, W}, title = {Hydrogen gas ameliorates acute alcoholic liver injury via anti-inflammatory and antioxidant effects and regulation of intestinal microbiota.}, journal = {International immunopharmacology}, volume = {120}, number = {}, pages = {110252}, doi = {10.1016/j.intimp.2023.110252}, pmid = {37196556}, issn = {1878-1705}, mesh = {Humans ; Mice ; Animals ; Antioxidants/therapeutic use/metabolism ; *Gastrointestinal Microbiome/physiology ; Liver/metabolism ; *Liver Diseases, Alcoholic ; Inflammation/metabolism ; Anti-Inflammatory Agents/therapeutic use/metabolism ; Mice, Inbred C57BL ; }, abstract = {Alcoholic liver disease (ALD) is a globally prevalent liver-related disorder characterized by severe oxidative stress and inflammatory liver damage, for which no effective treatment is currently available. Hydrogen gas (H2) has been demonstrated to be an efficient antioxidant in various diseases in animals as well as humans. However, the protective effects of H2 on ALD and its underlying mechanisms remain to be elucidated. The present study demonstrated that H2 inhalation ameliorated liver injury, and attenuated liver oxidative stress, inflammation, and steatosis in an ALD mouse model. Moreover, H2 inhalation improved gut microbiota, including increasing the abundance of Lachnospiraceae and Clostridia, and decreasing the abundance of Prevotellaceae and Muribaculaceae, and also improved intestinal barrier integrity. Mechanistically, H2 inhalation blocked activation of the LPS/TLR4/NF-κB pathway in liver. Notably, it was further demonstrated that the reshaped gut microbiota may accelerate alcohol metabolism, regulate lipid homeostasis and maintain immune balance by bacterial functional potential prediction (PICRUSt). Fecal microbiota transplantation from mice that had undergone H2 inhalation significantly alleviated acute alcoholic liver injury. In summary, the present study showed that H2 inhalation alleviated liver injury by reducing oxidative stress and inflammation, while also improving intestinal flora and enhancing the intestinal barrier. H2 inhalation may serve as an effective intervention for preventing and treating ALD in a clinical context.}, }
@article {pmid37193034, year = {2023}, author = {Huang, X and Zhang, Y and Huang, J and Gao, W and Yongfang, X and Zeng, C and Gao, C}, title = {The effect of FMT and vitamin C on immunity-related genes in antibiotic-induced dysbiosis in mice.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e15356}, pmid = {37193034}, issn = {2167-8359}, mesh = {Animals ; Mice ; *Anti-Bacterial Agents/adverse effects ; *Fecal Microbiota Transplantation ; Ascorbic Acid/pharmacology ; Dysbiosis/chemically induced ; Feces/microbiology ; Vitamins ; }, abstract = {Antibiotics are double-edged swords. Although antibiotics are used to inhibit pathogenic bacteria, they also run the risk of destroying some of the healthy bacteria in our bodies. We examined the effect of penicillin on the organism through a microarray dataset, after which 12 genes related to immuno-inflammatory pathways were selected by reading the literature and validated using neomycin and ampicillin. The expression of genes was measured using qRT-PCR. Several genes were significantly overexpressed in antibiotic-treated mice, including CD74 and SAA2 in intestinal tissues that remained extremely expressed after natural recovery. Moreover, transplantation of fecal microbiota from healthy mice to antibiotic-treated mice was made, where GZMB, CD3G, H2-AA, PSMB9, CD74, and SAA1 were greatly expressed; however, SAA2 was downregulated and normal expression was restored, and in liver tissue, SAA1, SAA2, SAA3 were extremely expressed. After the addition of vitamin C, which has positive effects in several aspects, to the fecal microbiota transplantation, in the intestinal tissues, the genes that were highly expressed after the fecal microbiota transplantation effectively reduced their expression, and the unaffected genes remained normally expressed, but the CD74 gene remained highly expressed. In liver tissues, normally expressed genes were not affected, but the expression of SAA1 was reduced and the expression of SAA3 was increased. In other words, fecal microbiota transplantation did not necessarily bring about a positive effect of gene expression restoration, but the addition of vitamin C effectively reduced the effects of fecal microbiota transplantation and regulated the balance of the immune system.}, }
@article {pmid37192676, year = {2023}, author = {Meng, Y and Sun, J and Zhang, G}, title = {Fecal microbiota transplantation holds the secret to youth.}, journal = {Mechanisms of ageing and development}, volume = {212}, number = {}, pages = {111823}, doi = {10.1016/j.mad.2023.111823}, pmid = {37192676}, issn = {1872-6216}, mesh = {Humans ; Adolescent ; Fecal Microbiota Transplantation ; *Diabetes Mellitus, Type 2 ; *Inflammatory Bowel Diseases/microbiology/therapy ; *Gastrointestinal Microbiome ; *Microbiota ; *Metabolic Diseases ; Bacteria ; }, abstract = {Aging shows itself not just at the cellular level, with shortened telomeres and cell cycle arrest, but also at the organ and organismal level, with diminished brainpower, dry eyes, intestinal inflammation, muscular atrophy, wrinkles, etc. When the gut microbiota, often called the "virtual organ of the host," fails to function normally, it can lead to a cascade of health problems including, but not limited to, inflammatory bowel disease, obesity, metabolic liver disease, type II diabetes, cardiovascular disease, cancer, and even neurological disorders. An effective strategy for restoring healthy gut bacteria is fecal microbiota transplantation (FMT). It can reverse the effects of aging on the digestive system, the brain, and the vision by transplanting the functional bacteria found in the excrement of healthy individuals into the gut tracts of patients. This paves the way for future research into using the microbiome as a therapeutic target for disorders associated with aging.}, }
@article {pmid37192552, year = {2023}, author = {Liu, J and Cai, J and Fan, P and Dong, X and Zhang, N and Tai, J and Cao, Y}, title = {Salidroside protects mice from high-fat diet-induced obesity by modulating the gut microbiota.}, journal = {International immunopharmacology}, volume = {120}, number = {}, pages = {110278}, doi = {10.1016/j.intimp.2023.110278}, pmid = {37192552}, issn = {1878-1705}, mesh = {Animals ; Mice ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Mice, Obese ; RNA, Ribosomal, 16S ; Obesity/metabolism ; Inflammation/complications ; Mice, Inbred C57BL ; }, abstract = {Obesity is a systemic disease with multisystem inflammation associated with gut dysbiosis. Salidroside (SAL) which is a major glycoside extracted from Rhodiola rosea L. has a wide range of pharmacological effects, but the role of gut microbiota in the protective effects of SAL on obesity has not been studied. Herein, we aim to explore whether SAL could ameliorate high-fat diet (HFD)-induced obesity in mice by modulating microbiota. Results showed that oral treatment with SAL alleviated HFD-induced obesity in mice as evidenced by body weight and fat weight. SAL supplementation effectively attenuated fat accumulation, lipid synthesis genes expression, liver inflammation, and metabolic endotoxemia. In addition, SAL treatment alleviated intestinal damage and increased the expression of mucin protein (Mucin-2) and tight junction (TJ) proteins (Occludin and Zonula Occludens-1). 16S rRNA sequencing analysis revealed that the gut microbiota of obese mice was also partly improved by SAL via restoring the microbial community structure and diversity. A fecal microbiota transplantation (FMT) study was designed to verify the causality. Compared with fecal transplantation (FM) from the HFD-treated mice, FM from the SAL-treated mice significantly mitigate the symptoms of obese mice, including decreasing body weight, fat accumulation, and attenuating pathological damage in the gut. Thus, SAL could be a remarkable candidate to prevent obesity.}, }
@article {pmid37191418, year = {2023}, author = {Zou, B and Li, J and Ma, RX and Cheng, XY and Ma, RY and Zhou, TY and Wu, ZQ and Yao, Y and Li, J}, title = {Gut Microbiota is an Impact Factor based on the Brain-Gut Axis to Alzheimer's Disease: A Systematic Review.}, journal = {Aging and disease}, volume = {14}, number = {3}, pages = {964-1678}, pmid = {37191418}, issn = {2152-5250}, abstract = {Alzheimer's disease (AD) is a degenerative disease of the central nervous system. The pathogenesis of AD has been explained using cholinergic, β-amyloid toxicity, tau protein hyperphosphorylation, and oxidative stress theories. However, an effective treatment method has not been developed. In recent years, with the discovery of the brain-gut axis (BGA) and breakthroughs made in Parkinson's disease, depression, autism, and other diseases, BGA has become a hotspot in AD research. Several studies have shown that gut microbiota can affect the brain and behavior of patients with AD, especially their cognitive function. Animal models, fecal microbiota transplantation, and probiotic intervention also provide evidence regarding the correlation between gut microbiota and AD. This article discusses the relationship and related mechanisms between gut microbiota and AD based on BGA to provide possible strategies for preventing or alleviating AD symptoms by regulating gut microbiota.}, }
@article {pmid37191003, year = {2024}, author = {Jiang, H and Ye, Y and Wang, M and Sun, X and Sun, T and Chen, Y and Li, P and Zhang, M and Wang, T}, title = {The progress on the relationship between gut microbiota and immune checkpoint blockade in tumors.}, journal = {Biotechnology &amp; genetic engineering reviews}, volume = {40}, number = {4}, pages = {4446-4465}, doi = {10.1080/02648725.2023.2212526}, pmid = {37191003}, issn = {2046-5556}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Neoplasms/immunology/therapy/microbiology/drug therapy ; *Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy/methods ; Animals ; }, abstract = {Immune checkpoint blockade (ICB) has emerged as a promising immunotherapeutic approach for the treatment of various tumors. However, the efficacy of this therapy is limited in a subset of patients, and it is important to develop strategies to enhance immune responses. Studies have demonstrated a critical role of gut microbiota in regulating the therapeutic response to ICB. Gut microbiota composition, diversity, and function are mediated by metabolites, such as short-chain fatty acids and secondary bile acids, that interact with host immune cells through specific receptors. In addition, gut bacteria may translocate to the tumor site and stimulate antitumor immune responses. Therefore, maintaining a healthy gut microbiota composition, for instance through avoiding the use of antibiotics or probiotic interventions, can be an effective approach to optimize ICB therapy. This review summarizes the current understanding of the microbiota-immunity interactions in the context of ICB therapy, and discusses potential clinical implications of these findings.}, }
@article {pmid37189804, year = {2023}, author = {Tews, HC and Elger, T and Grewal, T and Weidlich, S and Vitali, F and Buechler, C}, title = {Fecal and Urinary Adipokines as Disease Biomarkers.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, pmid = {37189804}, issn = {2227-9059}, abstract = {The use of biomarkers is of great clinical value for the diagnosis and prognosis of disease and the assessment of treatment efficacy. In this context, adipokines secreted from adipose tissue are of interest, as their elevated circulating levels are associated with a range of metabolic dysfunctions, inflammation, renal and hepatic diseases and cancers. In addition to serum, adipokines can also be detected in the urine and feces, and current experimental evidence on the analysis of fecal and urinary adipokine levels points to their potential as disease biomarkers. This includes increased urinary adiponectin, lipocalin-2, leptin and interleukin-6 (IL-6) levels in renal diseases and an association of elevated urinary chemerin as well as urinary and fecal lipocalin-2 levels with active inflammatory bowel diseases. Urinary IL-6 levels are also upregulated in rheumatoid arthritis and may become an early marker for kidney transplant rejection, while fecal IL-6 levels are increased in decompensated liver cirrhosis and acute gastroenteritis. In addition, galectin-3 levels in urine and stool may emerge as a biomarker for several cancers. With the analysis of urine and feces from patients being cost-efficient and non-invasive, the identification and utilization of adipokine levels as urinary and fecal biomarkers could become a great advantage for disease diagnosis and predicting treatment outcomes. This review article highlights data on the abundance of selected adipokines in urine and feces, underscoring their potential to serve as diagnostic and prognostic biomarkers.}, }
@article {pmid37189634, year = {2023}, author = {Boicean, A and Birlutiu, V and Ichim, C and Anderco, P and Birsan, S}, title = {Fecal Microbiota Transplantation in Inflammatory Bowel Disease.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, pmid = {37189634}, issn = {2227-9059}, abstract = {Inflammatory bowel diseases represent a complex array of diseases of incompletely known etiology that led to gastrointestinal tract chronic inflammation. In inflammatory bowel disease, a promising method of treatment is represented by fecal microbiota transplantation (FMT), FMT has shown its increasing effectiveness and safety in recent years for recurrent CDI; moreover, it showed real clinical benefits in treating SARS-CoV-2 and CDI co-infection. Crohn's disease and ulcerative colitis are characterized by immune dysregulation, resulting in digestive tract damage caused by immune responses. Most current therapeutic strategies are associated with high costs and many adverse effects by directly targeting the immune response, so modifying the microbial environment by FMT offers an alternative approach that could indirectly influence the host's immune system in a safe way. Studies outline the endoscopic and clinical improvements in UC and CD in FMT patients versus control groups. This review outlines the multiple benefits of FMT in the case of IBD by improving patients unbalanced gut, therefore improving endoscopic and clinical symptomatology. We aim to emphasize the clinical importance and benefits of FMT in order to prevent flares or complications of IBD and to highlight that further validation is needed for establishing a clinical protocol for FMT in IBD.}, }
@article {pmid37187187, year = {2024}, author = {Stallmach, A and von Müller, L and Storr, M and Link, A and Konturek, PC and Solbach, PC and Weiss, KH and Wahler, S and Vehreschild, MJGT}, title = {[Fecal Microbiota Transfer (FMT) in Germany - Status and Perspective].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {62}, number = {4}, pages = {490-499}, doi = {10.1055/a-2075-2725}, pmid = {37187187}, issn = {1439-7803}, mesh = {Humans ; Female ; Aged ; Male ; Fecal Microbiota Transplantation/methods ; *Clostridioides difficile ; *Clostridium Infections/therapy ; *Gastrointestinal Microbiome ; Germany/epidemiology ; Treatment Outcome ; Recurrence ; }, abstract = {INTRODUCTION: Fecal microbiota transfer (FMT) is a treatment to modulate the gastrointestinal microbiota. Its use in recurrent Clostridioides difficile infection (rCDI) is established throughout Europe and recommended in national and international guidelines. In Germany, the FMT is codeable in the hospital reimbursement system. A comprehensive survey on the frequency of use based on this coding is missing so far.<br><br>MATERIAL AND METHODOLOGY: Reports of the Institute for Hospital Remuneration (InEK), the Federal Statistical Office (DESTATIS), and hospital quality reports 2015-2021 were examined for FMT coding and evaluated in a structured expert consultation.<br><br>RESULTS: Between 2015 and 2021, 1,645 FMT procedures were coded by 175 hospitals. From 2016 to 2018, this was a median of 293 (274-313) FMT annually, followed by a steady decline in subsequent years to 119 FMT in 2021. Patients with FMT were 57.7% female, median age 74 years, and FMT was applied colonoscopically in 72.2%. CDI was the primary diagnosis in 86.8% of cases, followed by ulcerative colitis in 7.6%.<br><br>DISCUSSION: In Germany, FMT is used less frequently than in the European comparison. One application hurdle is the regulatory classification of FMT as a non-approved drug, which leads to significantly higher costs in manufacturing and administration and makes reimbursement difficult. The European Commission recently proposed a regulation to classify FMT as a transplant. This could prospectively change the regulatory situation of FMT in Germany and thus contribute to a nationwide offer of a therapeutic procedure recommended in guidelines.}, }
@article {pmid37185024, year = {2023}, author = {Lukáčová, I and Ambro, &#x13d; and Dubayová, K and Mareková, M}, title = {The gut microbiota, its relationship to the immune system, and possibilities of its modulation.}, journal = {Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne}, volume = {72}, number = {1}, pages = {40-53}, pmid = {37185024}, issn = {1210-7913}, mesh = {Humans ; *Gastrointestinal Microbiome ; Immune System ; Bacteria ; Fecal Microbiota Transplantation ; }, abstract = {Research of the gut microbiota allows a better understanding of its composition and function and reveals the links between changes in the composition of bacteria and various intestinal but also systemic diseases. The gut microbiota performs several of important functions in the host body and influences many physiological processes. Gut bacteria synthesize many compounds needed for the proper function of the body (e.g., vitamins, short-chain fatty acids, and amino acids). They help maintain the integrity of the intestinal barrier and protect against pathogens. The gut microbiota plays a crucial role in the development and function of the immune system. Significant changes in the composition of the intestinal microbiota led to a dysbiotic state and the loss of its beneficial functions for humans. The review article summarizes the basic knowledge about the composition and function of the bacterial gut microbiota in healthy people, its role in the development of the immune system, and the mechanisms involved in maintaining homeostasis. It also presents current knowledge about the possibility of targeted modulation of the bacterial gut microbiota and faecal transplantation.}, }
@article {pmid37180433, year = {2023}, author = {Fan, H and Liu, X and Ren, Z and Fei, X and Luo, J and Yang, X and Xue, Y and Zhang, F and Liang, B}, title = {Gut microbiota and cardiac arrhythmia.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1147687}, pmid = {37180433}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation ; Arrhythmias, Cardiac ; Dysbiosis/therapy ; }, abstract = {One of the most prevalent cardiac diseases is cardiac arrhythmia, however the underlying causes are not entirely understood. There is a lot of proof that gut microbiota (GM) and its metabolites have a significant impact on cardiovascular health. In recent decades, intricate impacts of GM on cardiac arrythmia have been identified as prospective approaches for its prevention, development, treatment, and prognosis. In this review, we discuss about how GM and its metabolites might impact cardiac arrhythmia through a variety of mechanisms. We proposed to explore the relationship between the metabolites produced by GM dysbiosis including short-chain fatty acids(SCFA), Indoxyl sulfate(IS), trimethylamine N-oxide(TMAO), lipopolysaccharides(LPS), phenylacetylglutamine(PAGln), bile acids(BA), and the currently recognized mechanisms of cardiac arrhythmias including structural remodeling, electrophysiological remodeling, abnormal nervous system regulation and other disease associated with cardiac arrythmia, detailing the processes involving immune regulation, inflammation, and different types of programmed cell death etc., which presents a key aspect of the microbial-host cross-talk. In addition, how GM and its metabolites differ and change in atrial arrhythmias and ventricular arrhythmias populations compared with healthy people are also summarized. Then we introduced potential therapeutic strategies including probiotics and prebiotics, fecal microbiota transplantation (FMT) and immunomodulator etc. In conclusion, the GM has a significant impact on cardiac arrhythmia through a variety of mechanisms, offering a wide range of possible treatment options. The discovery of therapeutic interventions that reduce the risk of cardiac arrhythmia by altering GM and metabolites is a real challenge that lies ahead.}, }
@article {pmid37179170, year = {2023}, author = {Xin, Y and Huang, C and Zheng, M and Zhou, W and Zhang, B and Zhao, M and Lu, Q}, title = {Fecal microbiota transplantation in the treatment of systemic lupus erythematosus: What we learnt from the explorative clinical trial.}, journal = {Journal of autoimmunity}, volume = {141}, number = {}, pages = {103058}, doi = {10.1016/j.jaut.2023.103058}, pmid = {37179170}, issn = {1095-9157}, mesh = {Animals ; Humans ; Mice ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; *Lupus Erythematosus, Systemic ; *Microbiota ; }, abstract = {Systemic lupus erythematosus (SLE) is an autoimmune disease with the characterized presence of autoantibodies and resulting in multiple organ damage, which is incurable and can be lethal. The current treatments are limited and less progress has been made in drug discovery for the last few decades. Researches imply that gut dysbiosis exists in both patients and murine models with SLE, taking part in the pathogenesis of SLE through multiple mechanisms such as microbiota translocation and molecular mimicry. Intestinal interventions on the gut microbiome by fecal transplantations to reconstitute the gut-immunity homeostasis serve as a novel therapeutic option for SLE patients. Fecal microbiota transplantation (FMT), which is usually used in intestinal diseases, has been firstly demonstrated to be safe and efficient in recovering gut microbiota structure of SLE patients and reducing lupus activity in our recent clinical trial, which is the first trial testing FMT therapy in SLE treatment. In this paper, we reviewed the results of the single-arm clinical trial and made recommendations on FMT practice in SLE treatment including therapeutic indications, screening items and dosage regimen, trying to provide references for future study and clinical practice. We also came up with the unanswered questions that need to be solved by the ongoing randomized controlled trial as well as the future expectations for the intestinal intervention strategies of SLE patients.}, }
@article {pmid37179169, year = {2023}, author = {Zhang, B and Zhou, W and Liu, Q and Huang, C and Hu, Z and Zheng, M and Xin, Y and Zhao, M and Lu, Q}, title = {Effects of fecal microbiota transplant on DNA methylation in patients with systemic lupus erythematosus.}, journal = {Journal of autoimmunity}, volume = {141}, number = {}, pages = {103047}, doi = {10.1016/j.jaut.2023.103047}, pmid = {37179169}, issn = {1095-9157}, mesh = {Humans ; *DNA Methylation ; Fecal Microbiota Transplantation ; Interferon-Induced Helicase, IFIH1/genetics ; Leukocytes, Mononuclear ; *Lupus Erythematosus, Systemic/genetics/therapy ; }, abstract = {Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterized by multiple organ damage accompanied by the over-production of autoantibodies. Decreased intestinal flora diversity and disruption of homeostasis have been proven to be associated with pathogenesis of SLE. In previous study, a clinical trial was conducted to verify the safety and effectiveness of fecal microbiota transplantation (FMT) in the treatment of SLE. To explore the mechanism of FMT in the treatment of SLE, we included 14 SLE patients participating in clinical trials, including 8 in responders group (Rs) and 6 in non-responders group (NRs), and collected peripheral blood DNA and serum. We found that the serum of S-adenosylmethionine (SAM), methylation group donor, was upregulated after FMT, accompanied by an increase in genome-wide DNA methylation level in Rs. We further showed that the methylation levels in promoter regions of Interferon-γ (IFN-γ), induced Helicase C Domain Containing Protein 1 (IFIH1), endoplasmic reticulum membrane protein complex 8 (EMC8), and Tripartite motif-containing protein 58 (TRIM58) increased after FMT treatment. On the contrary, there was no significant change in the methylation of IFIH1 promoter region in the NRs after FMT, and the methylation level of IFIH1 in the Rs was significantly higher than that in the NRs at week 0. We included 850 K methylation chip sequencing, combining previous data of metagenomic sequencing, and metabolomic sequencing for multi-omics analysis to discuss the relationship between flora-metabolite-methylation in FMT. Finally, we found that hexanoic acid treatment can up-regulate the global methylation of peripheral blood mononuclear cells in SLE patients. Overall, our results delineate changes in methylation level after FMT treatment of SLE and reveal possible mechanisms of FMT treatment in terms of the recovery of abnormal hypomethylation.}, }
@article {pmid37169290, year = {2023}, author = {Gray, AN and DeFilipp, Z}, title = {Fecal Microbiota Transplantation for Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation: Expanding the Horizon into Pediatrics.}, journal = {Transplantation and cellular therapy}, volume = {29}, number = {8}, pages = {484-491}, doi = {10.1016/j.jtct.2023.05.007}, pmid = {37169290}, issn = {2666-6367}, mesh = {Adult ; Humans ; Child ; Fecal Microbiota Transplantation ; *Graft vs Host Disease/therapy ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; *Hematopoietic Stem Cell Transplantation/adverse effects ; }, abstract = {The microbiome plays a vital role in maintaining homeostasis of the intestinal microenvironment and the immune response in allogeneic hematopoietic cell transplantation (HCT) recipients. Disruption of the intestinal microbiome has been associated with the development of acute graft-versus-host disease (GVHD) of the lower gastrointestinal tract and worse survival. Fecal microbiota transplantation (FMT) can achieve clinical responses in refractory GVHD, establishing the promise of microbiome-directed interventions in this population. Although most data on microbial changes in HCT recipients have been generated from the adult population, children with refractory GVHD represent an important group that may benefit from FMT. In this review, we first highlight characteristics that distinguish the pediatric intestinal microbiome from the adult intestinal microbiome. We then explore multiple clinical factors that warrant careful consideration to optimize the application of FMT and other microbiome-directed therapeutics to children.}, }
@article {pmid37168868, year = {2023}, author = {Satish, S and Abu, Y and Gomez, D and Kumar Dutta, R and Roy, S}, title = {HIV, opioid use, and alterations to the gut microbiome: elucidating independent and synergistic effects.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1156862}, pmid = {37168868}, issn = {1664-3224}, support = {F31 DA053795/DA/NIDA NIH HHS/United States ; R01 DA043252/DA/NIDA NIH HHS/United States ; R01 DA044582/DA/NIDA NIH HHS/United States ; R01 DA047089/DA/NIDA NIH HHS/United States ; R01 DA050542/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Analgesics, Opioid/therapeutic use ; HIV ; Dysbiosis/microbiology ; *HIV Infections/drug therapy/microbiology ; Inflammation ; Clostridiales ; *Opioid-Related Disorders ; }, abstract = {BACKGROUND: The microbiome is essential to immune development, defense against pathogens, and modulation of inflammation. Microbial dysbiosis has been reported in various diseases including human immunodeficiency virus (HIV) and opioid use disorder (OUD). Notably, people living with HIV (PLWH) have been reported to both have higher rates of OUD and use opioids at higher rates than the general public. Thus, studying gut microbial alterations in people living with HIV and with OUD could elucidate mechanisms pertaining to how these conditions both shape and are shaped by the microbiome. However, to date few studies have investigated how HIV and OUD in combination impact the microbiome.<br><br>AIM OF REVIEW: Here, we review previous studies outlining interactions between HIV, opioid use, and microbial dysbiosis and describe attempts to treat this dysbiosis with fecal microbial transplantation, probiotics, and dietary changes.<br><br>While the limited number of studies prevent overgeneralizations; accumulating data suggest that HIV and opioid use together induce distinct alterations in the gut microbiome. Among the three existing preclinical studies of HIV and opioid use, two studies reported a decrease in Lachnospiraceae and Ruminococcaceae, and one study reported a decrease in Muribaculaceae in the combined HIV and opioid group relative to HIV-alone, opioid-alone, or control groups. These bacteria are known to modulate immune function, decrease colonic inflammation, and maintain gut epithelial barrier integrity in healthy individuals. Accordingly, modulation of the gut microbiome to restore gut homeostasis may be attempted to improve both conditions. While mixed results exist regarding treating dysbiosis with microbial restoration in PLWH or in those with opioid dependency, larger well-defined studies that can improve microbial engraftment in hosts hold much promise and should still be explored.}, }
@article {pmid37167953, year = {2023}, author = {Porcari, S and Benech, N and Valles-Colomer, M and Segata, N and Gasbarrini, A and Cammarota, G and Sokol, H and Ianiro, G}, title = {Key determinants of success in fecal microbiota transplantation: From microbiome to clinic.}, journal = {Cell host &amp; microbe}, volume = {31}, number = {5}, pages = {712-733}, doi = {10.1016/j.chom.2023.03.020}, pmid = {37167953}, issn = {1934-6069}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Clostridioides difficile ; *Microbiota ; Feces ; *Gastrointestinal Microbiome ; *Clostridium Infections/therapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has achieved satisfactory results in preventing the recurrence of Clostridioides difficile infection, but these positive outcomes have only been partially replicated in other diseases. Several factors influence FMT success, including those related to donors and recipients (including diversity and specific composition of the gut microbiome, immune system, and host genetics) as well as to working protocols (fecal amount and number of infusions, route of delivery, and adjuvant treatments). Moreover, initial evidence suggests that the clinical success of FMT may be related to the degree of donor microbial engraftment. The application of cutting-edge technologies for microbiome assessment, along with changes in the current vision of fecal transplants, are expected to improve FMT protocols and outcomes. Here, we review the key determinants of FMT success and insights and strategies that will enable a close integration of lab-based and clinical approaches for increasing FMT success.}, }
@article {pmid37167952, year = {2023}, author = {Yadegar, A and Pakpoor, S and Ibrahim, FF and Nabavi-Rad, A and Cook, L and Walter, J and Seekatz, AM and Wong, K and Monaghan, TM and Kao, D}, title = {Beneficial effects of fecal microbiota transplantation in recurrent Clostridioides difficile infection.}, journal = {Cell host &amp; microbe}, volume = {31}, number = {5}, pages = {695-711}, pmid = {37167952}, issn = {1934-6069}, support = {K01 DK111794/DK/NIDDK NIH HHS/United States ; P20 GM109094/GM/NIGMS NIH HHS/United States ; P20 GM146584/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation/methods ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Treatment Outcome ; Recurrence ; }, abstract = {Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI). However, the mechanisms underpinning its clinical efficacy are incompletely understood. Herein, we provide an overview of rCDI pathogenesis followed by a discussion of potential mechanisms of action focusing on the current understanding of trans-kingdom microbial, metabolic, immunological, and epigenetic mechanisms. We then outline the current research gaps and offer methodological recommendations for future studies to elevate the quality of research and advance knowledge translation. By combining interventional trials with multiomics technology and host and environmental factors, analyzing longitudinally collected biospecimens will generate results that can be validated with animal and other models. Collectively, this will confirm causality and improve translation, ultimately to develop targeted therapies to replace FMT.}, }
@article {pmid37166426, year = {2023}, author = {Cheng, CH and Liu, YC and Yang, YSH and Lin, KJ and Wu, D and Liu, YR and Chang, CC and Hong, CT and Hu, CJ}, title = {Plasmon-activated water as a therapeutic strategy in Alzheimer's disease by altering gut microbiota.}, journal = {Aging}, volume = {15}, number = {9}, pages = {3715-3737}, pmid = {37166426}, issn = {1945-4589}, mesh = {Mice ; Animals ; *Alzheimer Disease/therapy/pathology ; *Gastrointestinal Microbiome/physiology ; Water ; Amyloid beta-Peptides ; Mice, Transgenic ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Disease Models, Animal ; }, abstract = {Gut microbiota (GM) are involved in the pathophysiology of Alzheimer's disease (AD) and might correlate to the machinery of the gut-brain axis. Alteration of the GM profiles becomes a potential therapy strategy in AD. Here, we found that plasmon-activated water (PAW) therapy altered GM profile and reduced AD symptoms in APPswe/PS1dE9 transgenic mice (AD mice). GM profile showed the difference between AD and WT mice. PAW therapy in AD mice altered GM profile and fecal microbiota transplantation (FMT) reproduced GM profile in AD mice. PAW therapy and FMT in AD mice reduced cognitive decline and amyloid accumulation by novel object recognition (NOR) test and amyloid PET imaging. Immunofluorescent staining and western blot analysis of β-amyloid (Aβ) and phosphorylated (p)-tau in the brain of AD mice were reduced in PAW therapy and FMT. The inflammatory markers, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α and pro-inflammatory indicator of arginase-1/CD86 ratio were also reduced. Furthermore, immunohistochemistry (IHC) analysis of occludin and claudin-5 in the intestine and AXL in the brain were increased to correlate with the abundant GM in PAW therapy and FMT. Our results showed the machinery of gut-brain axis, and PAW might be a potential therapeutic strategy in AD.}, }
@article {pmid37166218, year = {2023}, author = {Li, H and Li, Y and Qian, J}, title = {What is the "optimal formula" for donor selection and feces processing for fecal microbiota transplantation in ulcerative colitis?.}, journal = {Chinese medical journal}, volume = {136}, number = {12}, pages = {1410-1412}, pmid = {37166218}, issn = {2542-5641}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy ; Donor Selection ; Feces ; *Gastrointestinal Microbiome ; Treatment Outcome ; }, }
@article {pmid37164760, year = {2023}, author = {Lim, EY and Song, EJ and Shin, HS}, title = {Gut Microbiome as a Possible Cause of Occurrence and Therapeutic Target in Chronic Obstructive Pulmonary Disease.}, journal = {Journal of microbiology and biotechnology}, volume = {33}, number = {9}, pages = {1111-1118}, pmid = {37164760}, issn = {1738-8872}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics ; Inflammation ; *Pulmonary Disease, Chronic Obstructive/therapy ; Dysbiosis/therapy ; }, abstract = {As a long-term condition that affects the airways and lungs, chronic obstructive pulmonary disease (COPD) is characterized by inflammation, emphysema, breathlessness, chronic cough, and sputum production. Currently, the bronchodilators and anti-inflammatory drugs prescribed for COPD are mostly off-target, warranting new disease management strategies. Accumulating research has revealed the gut-lung axis to be a bidirectional communication system. Cigarette smoke, a major exacerbating factor in COPD and lung inflammation, affects gut microbiota composition and diversity, causing gut microbiota dysbiosis, a condition that has recently been described in COPD patients and animal models. For this review, we focused on the gut-lung axis, which is influenced by gut microbial metabolites, bacterial translocation, and immune cell modulation. Further, we have summarized the findings of preclinical and clinical studies on the association between gut microbiota and COPD to provide a basis for using gut microbiota in therapeutic strategies against COPD. Our review also proposes that further research on probiotics, prebiotics, short-chain fatty acids, and fecal microbiota transplantation could assist therapeutic approaches targeting the gut microbiota to alleviate COPD.}, }
@article {pmid37163080, year = {2023}, author = {Sadler, KE and Atkinson, SN and Ehlers, VL and Waltz, TB and Hayward, M and Rodríguez García, DM and Salzman, NH and Stucky, CL and Brandow, AM}, title = {Gut microbiota and metabolites drive chronic sickle cell disease pain.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37163080}, issn = {2692-8205}, support = {R00 HL155791/HL/NHLBI NIH HHS/United States ; T32 GM080202/GM/NIGMS NIH HHS/United States ; }, abstract = {Pain is a debilitating symptom and leading reason for hospitalization of individuals with sickle cell disease. Chronic sickle cell pain is poorly managed because the biological basis is not fully understood. Using transgenic sickle cell mice and fecal material transplant, we determined that the gut microbiome drives persistent sickle cell pain. In parallel patient and mouse analyses, we identified bilirubin as one metabolite that induces sickle cell pain by altering vagus nerve activity. Furthermore, we determined that decreased abundance of the gut bacteria Akkermansia mucinophila is a critical driver of chronic sickle cell pain. These experiments demonstrate that the sickle cell gut microbiome drives chronic widespread pain and identify bacterial species and metabolites that should be targeted for chronic sickle cell disease pain management.}, }
@article {pmid37162960, year = {2024}, author = {Carr, A and Baliga, NS and Diener, C and Gibbons, SM}, title = {Personalized Clostridioides difficile engraftment risk prediction and probiotic therapy assessment in the human gut.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37162960}, issn = {2692-8205}, support = {R01 DK133468/DK/NIDDK NIH HHS/United States ; }, abstract = {Clostridioides difficile colonizes up to 30-40% of community-dwelling adults without causing disease. C. difficile infections (CDIs) are the leading cause of antibiotic-associated diarrhea in the U.S. and typically develop in individuals following disruption of the gut microbiota due to antibiotic or chemotherapy treatments. Further treatment of CDI with antibiotics is not always effective and can lead to antibiotic resistance and recurrent infections (rCDI). The most effective treatment for rCDI is the reestablishment of an intact microbiota via fecal microbiota transplants (FMTs). However, the success of FMTs has been difficult to generalize because the microbial interactions that prevent engraftment and facilitate the successful clearance of C. difficile are still only partially understood. Here we show how microbial community-scale metabolic models (MCMMs) accurately predicted known instances of C. difficile colonization susceptibility or resistance in vitro and in vivo. MCMMs provide detailed mechanistic insights into the ecological interactions that govern C. difficile engraftment, like cross-feeding or competition involving metabolites like succinate, trehalose, and ornithine, which differ from person to person. Indeed, three distinct C. difficile metabolic niches emerge from our MCMMs, two associated with positive growth rates and one that represents non-growth, which are consistently observed across 15,204 individuals from five independent cohorts. Finally, we show how MCMMs can predict personalized engraftment and C. difficile growth suppression for a probiotic cocktail (VE303) designed to replace FMTs for the treatment rCDI. Overall, this powerful modeling approach predicts personalized C. difficile engraftment risk and can be leveraged to assess probiotic treatment efficacy. MCMMs could be extended to understand the mechanistic underpinnings of personalized engraftment of other opportunistic bacterial pathogens, beneficial probiotic organisms, or more complex microbial consortia.}, }
@article {pmid37162338, year = {2023}, author = {Naz, F and Petri, WA}, title = {Host Immunity and Immunization Strategies for Clostridioides difficile Infection.}, journal = {Clinical microbiology reviews}, volume = {36}, number = {2}, pages = {e0015722}, pmid = {37162338}, issn = {1098-6618}, support = {R01 AI124214/AI/NIAID NIH HHS/United States ; R01 AI152477/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Clostridioides difficile ; Immunity, Innate ; Vaccination ; *Clostridium Infections/prevention &amp; control ; }, abstract = {Clostridioides difficile infection (CDI) represents a significant challenge to public health. C. difficile-associated mortality and morbidity have led the U.S. CDC to designate it as an urgent threat. Moreover, recurrence or relapses can occur in up to a third of CDI patients, due in part to antibiotics being the primary treatment for CDI and the major cause of the disease. In this review, we summarize the current knowledge of innate immune responses, adaptive immune responses, and the link between innate and adaptive immune responses of the host against CDI. The other major determinants of CDI, such as C. difficile toxins, the host microbiota, and related treatments, are also described. Finally, we discuss the known therapeutic approaches and the current status of immunization strategies for CDI, which might help to bridge the knowledge gap in the generation of therapy against CDI.}, }
@article {pmid37161478, year = {2023}, author = {Raeisi, H and Noori, M and Azimirad, M and Mohebbi, SR and Asadzadeh Aghdaei, H and Yadegar, A and Zali, MR}, title = {Emerging applications of phage therapy and fecal virome transplantation for treatment of Clostridioides difficile infection: challenges and perspectives.}, journal = {Gut pathogens}, volume = {15}, number = {1}, pages = {21}, pmid = {37161478}, issn = {1757-4749}, support = {RIGLD 1138//Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran/ ; }, abstract = {Clostridioides difficile, which causes life-threatening diarrheal disease, is considered an urgent threat to healthcare setting worldwide. The current standards of care solely rely on conventional antibiotic treatment, however, there is a risk of promoting recurrent C. difficile infection (rCDI) because of the emergence of antibiotic-resistant strains. Globally, the alarming spread of antibiotic-resistant strains of C. difficile has resulted in a quest for alternative therapeutics. The use of fecal microbiota transplantation (FMT), which involves direct infusion of fecal suspension from a healthy donor into a diseased recipient, has been approved as a highly efficient therapeutic option for patients with rCDI. Bacteriophages or phages are a group of viruses that can infect and destroy bacterial hosts, and are recognized as the dominant viral component of the human gut microbiome. Accumulating data has demonstrated that phages play a vital role in microbial balance of the human gut microbiome. Recently, phage therapy and fecal virome transplantation (FVT) have been introduced as promising alternatives for the treatment of C. difficile -related infections, in particular drug-resistant CDI. Herein, we review the latest updates on C. difficile- specific phages, and phage-mediated treatments, and highlight the current and future prospects of phage therapy in the management of CDI.}, }
@article {pmid37160898, year = {2023}, author = {Pang, J and Raka, F and Heirali, AA and Shao, W and Liu, D and Gu, J and Feng, JN and Mineo, C and Shaul, PW and Qian, X and Coburn, B and Adeli, K and Ling, W and Jin, T}, title = {Resveratrol intervention attenuates chylomicron secretion via repressing intestinal FXR-induced expression of scavenger receptor SR-B1.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {2656}, pmid = {37160898}, issn = {2041-1723}, support = {R01 HL131597/HL/NHLBI NIH HHS/United States ; PJT159735//CIHR/Canada ; }, mesh = {Male ; Animals ; Mice ; Humans ; *Chylomicrons ; Resveratrol/pharmacology ; Caco-2 Cells ; *Polyphenols ; Receptors, Scavenger ; }, abstract = {Two common features of dietary polyphenols have hampered our mechanistic understanding of their beneficial effects for decades: targeting multiple organs and extremely low bioavailability. We show here that resveratrol intervention (REV-I) in high-fat diet (HFD)-challenged male mice inhibits chylomicron secretion, associated with reduced expression of jejunal but not hepatic scavenger receptor class B type 1 (SR-B1). Intestinal mucosa-specific SR-B1[-/-] mice on HFD-challenge exhibit improved lipid homeostasis but show virtually no further response to REV-I. SR-B1 expression in Caco-2 cells cannot be repressed by pure resveratrol compound while fecal-microbiota transplantation from mice on REV-I suppresses jejunal SR-B1 in recipient mice. REV-I reduces fecal levels of bile acids and activity of fecal bile-salt hydrolase. In Caco-2 cells, chenodeoxycholic acid treatment stimulates both FXR and SR-B1. We conclude that gut microbiome is the primary target of REV-I, and REV-I improves lipid homeostasis at least partially via attenuating FXR-stimulated gut SR-B1 elevation.}, }
@article {pmid37158970, year = {2023}, author = {Hu, J and Chen, J and Xu, X and Hou, Q and Ren, J and Yan, X}, title = {Gut microbiota-derived 3-phenylpropionic acid promotes intestinal epithelial barrier function via AhR signaling.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {102}, pmid = {37158970}, issn = {2049-2618}, mesh = {Animals ; Mice ; Swine ; *Gastrointestinal Microbiome ; Receptors, Aryl Hydrocarbon/genetics ; DNA, Ribosomal ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: The intestinal epithelial barrier confers protection against the intestinal invasion by pathogens and exposure to food antigens and toxins. Growing studies have linked the gut microbiota to the intestinal epithelial barrier function. The mining of the gut microbes that facilitate the function of intestinal epithelial barrier is urgently needed.<br><br>RESULTS: Here, we studied a landscape of the gut microbiome of seven pig breeds using metagenomics and 16S rDNA gene amplicon sequencing. The results indicated an obvious difference in the gut microbiome between Congjiang miniature (CM) pigs (a native Chinese breed) and commercial Duroc&#x2009;&#xd7;&#x2009;[Landrace&#x2009;&#xd7;&#x2009;Yorkshire] (DLY) pigs. CM finishing pigs had stronger intestinal epithelial barrier function than the DLY finishing pigs. Fecal microbiota transplantation from CM and DLY finishing pigs to germ-free (GF) mice transferred the intestinal epithelial barrier characteristics. By comparing the gut microbiome of the recipient GF mice, we identified and validated Bacteroides fragilis as a microbial species that contributes to the intestinal epithelial barrier. B. fragilis-derived 3-phenylpropionic acid metabolite had an important function on the enhancement of intestinal epithelial barrier. Furthermore, 3-phenylpropionic acid facilitated the intestinal epithelial barrier by activating aryl hydrocarbon receptor (AhR) signaling.<br><br>CONCLUSIONS: These findings suggest that manipulation of B. fragilis and 3-phenylpropionic acid is a promising strategy for improving intestinal epithelial barrier. Video Abstract.}, }
@article {pmid37156115, year = {2023}, author = {Liu, Y and Xu, L and Yang, Z and Wang, D and Li, T and Yang, F and Li, Z and Bai, X and Wang, Y}, title = {Gut-muscle axis and sepsis-induced myopathy: The potential role of gut microbiota.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {163}, number = {}, pages = {114837}, doi = {10.1016/j.biopha.2023.114837}, pmid = {37156115}, issn = {1950-6007}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Muscular Diseases/etiology/therapy ; Muscle, Skeletal/metabolism ; Muscular Atrophy/pathology ; *Sepsis/metabolism ; }, abstract = {Sepsis is described as an immune response disorder of the host to infection in which microorganisms play a non-negligible role. Most survivors of sepsis experience ICU-acquired weakness, also known as septic myopathy, characterized by skeletal muscle atrophy, weakness, and irreparable damage/regenerated or dysfunctional. The mechanism of sepsis-induced myopathy is currently unclear. It has been believed that this state is triggered by circulating pathogens and their related harmful factors, leading to impaired muscle metabolism. Sepsis and its resulting alterations in the intestinal microbiota are associated with sepsis-related organ dysfunction, including skeletal muscle wasting. There are also some studies on interventions targeting the flora, including fecal microbiota transplants, the addition of dietary fiber and probiotics in enteral feeding products, etc., aiming to improve sepsis-related myopathy. In this review, we critically assess the potential mechanisms and therapeutic prospects of intestinal flora in the development of septic myopathy.}, }
@article {pmid37154595, year = {2023}, author = {Long, J and Feng, Z and Zhou, H and Liu, J and Zhang, J and Ouyang, J}, title = {Assessing the Relationship Between Gut Microbiota and Posttransplant Diabetes Mellitus.}, journal = {Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation}, volume = {21}, number = {4}, pages = {350-360}, doi = {10.6002/ect.2022.0366}, pmid = {37154595}, issn = {2146-8427}, mesh = {Humans ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; *Kidney Transplantation/adverse effects ; *Diabetes Mellitus/diagnosis/etiology ; }, abstract = {OBJECTIVES: The incidence of diabetes significantly increases after kidney transplant, and the associated gut microbiota are closely related to diabetes. However, the gut microbiota of recipients with diabetes after kidney transplant remain unexplored.<br><br>MATERIALS AND METHODS: Feces samples from recipients with diabetes 3 months after kidney transplant were collected and analyzed using high-throughput 16S rRNA gene sequencing.<br><br>RESULTS: Our study included 45 transplant recipients: 23 posttransplant diabetes mellitus recipients, 11 recipients without diabetes mellitus, and 11 recipients with preexisting diabetes mellitus. No significant differences in intestinal flora richness and &#x3b1; diversity were observed among the 3 groups. However, principal coordinate analysis based on UniFrac distance revealed significant differences in &#x3b2; diversity. At the phyla level, the abundance of Proteobacteria in posttransplant diabetes mellitus recipients decreased (P = .028), whereas that of Bactericide (P = .004) increased. At the class level, the abundance of Gammaproteobacteria (P = .037) decreased, whereas thatofBacteroidia (P=.004)increased.Attheorderlevel, the abundanceof Enterobacteriales (P = .039)decreased, whereasBacteroidales (P=.004)increased.Atthe family level, the abundance of Enterobacteriaceae (P = .039) and Peptostreptococcaceae (P = .008) decreased, whereas Bacteroidaceae (P = .010) increased. At the genus level,the abundance of Lachnospiraceae incertae sedis (P = .008) decreased, whereas Bacteroides (P = .010) increased. Furthermore, KEGG analysis identified 33 pathways, among which the biosynthesis of unsaturated fatty acids was closely related to gut microbiota and posttransplant diabetes mellitus.<br><br>CONCLUSIONS: To our knowledge, this is the first comprehensive analysis of the gut microbiota from posttransplant diabetes mellitus recipients. The microbial composition of stool samples of post- transplant diabetes mellitus recipients was significantly different from recipients without diabetes and with preexisting diabetes. The number of bacteria producing short-chain fatty acids decreased, whereas pathogenic bacteria increased.}, }
@article {pmid37153213, year = {2023}, author = {Wu, X and Zhao, L and Zhang, Y and Li, K and Yang, J}, title = {The role and mechanism of the gut microbiota in the development and treatment of diabetic kidney disease.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1166685}, pmid = {37153213}, issn = {1664-042X}, abstract = {Diabetic kidney disease (DKD) is a common complication in patients with diabetes mellitus (DM). Increasing evidence suggested that the gut microbiota participates in the progression of DKD, which is involved in insulin resistance, renin-angiotensin system (RAS) activation, oxidative stress, inflammation and immunity. Gut microbiota-targeted therapies including dietary fiber, supplementation with probiotics or prebiotics, fecal microbiota transplantation and diabetic agents that modulate the gut microbiota, such as metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors. In this review, we summarize the most important findings about the role of the gut microbiota in the pathogenesis of DKD and the application of gut microbiota-targeted therapies.}, }
@article {pmid37151860, year = {2023}, author = {Galvao, FHF and Araki, J and Fonseca, ABS and Cruz, RJ and Lanchotte, C and Waisberg, DR and Chaib, E and Nacif, LS and Traldi, MCC and de Mello, EB and Andraus, W and Carneiro-D'Albuquerque, L}, title = {Multivisceral transplantation of pelvic organs in rats.}, journal = {Frontiers in surgery}, volume = {10}, number = {}, pages = {1086651}, pmid = {37151860}, issn = {2296-875X}, abstract = {BACKGROUND: Multivisceral transplantation of pelvic organs would be a potential treatment for severe pelvic floor dysfunction with fecal and urinary incontinence, extensive perineal trauma, or congenital disorders. Here, we describe the microsurgical technique of multivisceral transplantation of pelvic organs, including the pelvic floor, in rats.<br><br>DONOR OPERATION: We performed a perineal (including the genitalia, anus, muscles, and ligaments) and abdominal incision. The dissection progressed near the pelvic ring, dividing ligaments, muscles, external iliac vessels, and pudendal nerves, allowing pelvic floor mobilization. The aorta and vena cava were isolated distally, preserving the internal iliac and gonadal vessels. The graft containing the skin, muscles, ligaments, bladder, ureter, rectum, anus and vagina, uterus and ovarian (female), or penile, testis and its ducts (male) was removed en bloc, flushed, and cold-stored.<br><br>RECIPIENT OPERATION: The infrarenal aorta and vena cava were isolated and donor/recipient aorta-aorta and cava-cava end-to-side microanastomoses were performed. After pelvic floor and viscera removal, we performed microanastomoses between the donor and the recipient ureter, and the rectum and pudenda nerves. The pelvic floor was repositioned in its original position (orthotopic model) or the abdominal wall (heterotopic model). We sacrificed the animals 2 h after surgery.<br><br>RESULTS: We performed seven orthotopic and four heterotopic transplantations. One animal from the orthotopic model and one from the heterotopic model died because of technical failure. Six orthotopic and three heterotopic recipients survived up to 2&#x2005;h after transplantation.<br><br>CONCLUSION: The microsurgical technique for pelvic floor transplantation in rats is feasible, achieving an early survival rate of 81.82%.}, }
@article {pmid37151603, year = {2023}, author = {Lv, WJ and Huang, JY and Lin, J and Ma, YM and He, SQ and Zhang, YW and Wang, TZ and Cheng, K and Xiong, Y and Sun, FG and Pan, ZC and Sun, JB and Mao, W and Guo, SN}, title = {Phytosterols Alleviate Hyperlipidemia by Regulating Gut Microbiota and Cholesterol Metabolism in Mice.}, journal = {Oxidative medicine and cellular longevity}, volume = {2023}, number = {}, pages = {6409385}, pmid = {37151603}, issn = {1942-0994}, mesh = {Mice ; Animals ; *Phytosterols/pharmacology ; *Hyperlipidemias/drug therapy/metabolism ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics/metabolism ; Lipid Metabolism ; Cholesterol, LDL ; Liver/metabolism ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; }, abstract = {Phytosterols (PS) have been shown to regulate cholesterol metabolism and alleviate hyperlipidemia (HLP), but the mechanism is still unclear. In this study, we investigated the mechanism by which PS regulates cholesterol metabolism in high-fat diet (HFD) mice. The results showed that PS treatment reduced the accumulation of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the serum of HFD mice, while increasing the serum levels of high-density lipoprotein cholesterol (HDL-C). Compared with HFD mice, PS not only increased the antioxidant activity of the liver but also regulated the mRNA expression levels of enzymes and receptors related to cholesterol metabolism. The hypolipidemic effect of PS was abolished by antibiotic (Abx) intervention and reproduced by fecal transplantation (FMT) intervention. The results of 16S rRNA sequencing analysis showed that PS modulated the gut microbiota of mice. PS reduced the relative abundance of Lactobacillus and other bile salt hydrolase- (BSH-) producing gut microbiota in HFD mice, which are potentially related to cholesterol metabolism. These findings partially explain the mechanisms by which PS regulates cholesterol metabolism. This implies that regulation of the gut microbiota would be a potential target for the treatment of HLP.}, }
@article {pmid37150906, year = {2023}, author = {Rasmussen, TS and Mentzel, CMJ and Danielsen, MR and Jakobsen, RR and Zachariassen, LSF and Castro Mejia, JL and Brunse, A and Hansen, LH and Hansen, CHF and Hansen, AK and Nielsen, DS}, title = {Fecal virome transfer improves proliferation of commensal gut Akkermansia muciniphila and unexpectedly enhances the fertility rate in laboratory mice.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2208504}, pmid = {37150906}, issn = {1949-0984}, mesh = {Male ; Feces ; Birth Rate ; *Gastrointestinal Microbiome ; Infant ; Female ; Pregnancy ; Humans ; Animals ; Cell Proliferation ; Verrucomicrobia ; Mice, Inbred C57BL ; Akkermansia ; Virome ; Mice ; }, abstract = {Probiotics are intended to improve gastrointestinal health when consumed. However, the probiotics marketed today only colonize the densely populated gut to a limited extent. Bacteriophages comprise the majority of viruses in the human gut virome and there are strong indications that they play important roles in shaping the gut microbiome. Here, we investigate the use of fecal virome transplantation (FVT, sterile filtrated feces) as a mean to alter the gut microbiome composition to lead the way for persistent colonization of two types of probiotics: Lacticaseibacillus rhamnosus GG (LGG) representing a well-established probiotic and Akkermansia muciniphila (AKM) representing a putative next-generation probiotic. Male and female C57BL/6NTac mice were cohoused in pairs from 4 weeks of age and received the following treatment by oral gavage at week 5 and 6: AKM+FVT, LGG+FVT, probiotic sham (Pro-sham)+FVT, LGG+Saline, AKM+Saline, and control (Pro-sham+Saline). The FVT donor material originated from mice with high relative abundance of A. muciniphila. All animals were terminated at age 9 weeks. The FVT treatment did not increase the relative abundance of the administered LGG or AKM in the recipient mice. Instead FVT significantly (p < 0.05) increased the abundance of naturally occurring A. muciniphila compared to the control. This highlights the potential of propagating the existing commensal "probiotics" that have already permanently colonized the gut. Being co-housed male and female, a fraction of the female mice became pregnant. Unexpectedly, the FVT treated mice were found to have a significantly (p < 0.05) higher fertility rate independent of probiotic administration. These preliminary observations urge for follow-up studies investigating interactions between the gut microbiome and fertility.}, }
@article {pmid37150800, year = {2023}, author = {Emile, SH and Khan, SM and Garoufalia, Z and Silva-Alvarenga, E and Gefen, R and Horesh, N and Freund, MR and Wexner, SD}, title = {A network meta-analysis of surgical treatments of complete rectal prolapse.}, journal = {Techniques in coloproctology}, volume = {27}, number = {10}, pages = {787-797}, pmid = {37150800}, issn = {1128-045X}, mesh = {Humans ; *Rectal Prolapse/surgery/complications ; *Laparoscopy/methods ; Rectum/surgery ; *Digestive System Surgical Procedures/adverse effects ; *Fecal Incontinence/surgery/complications ; Surgical Mesh/adverse effects ; Recurrence ; Treatment Outcome ; Randomized Controlled Trials as Topic ; }, abstract = {PURPOSE: Surgical treatment of complete rectal prolapse can be undertaken via an abdominal or a perineal approach. The present network meta-analysis aimed to compare the outcomes of different abdominal and perineal procedures for rectal prolapse in terms of recurrence, complications, and improvement in fecal incontinence (FI).<br><br>METHODS: A PRISMA-compliant systematic review of PubMed, Scopus, and Web of Science was conducted. Randomized clinical trials comparing two or more procedures for the treatment of complete rectal prolapse were included. The risk of bias was assessed using the ROB-2 tool. The main outcomes were recurrence of full-thickness rectal prolapse, complications, operation time, and improvement in FI.<br><br>RESULTS: Nine randomized controlled trials with 728 patients were included. The follow-up ranged between 12 and 47&#xa0;months. Posterior mesh rectopexy had significantly lower odds of recurrence than did the Altemeier procedure (logOR, -&#x2009;12.75; &#x2009;95% credible intervals, -&#x2009;40.91,&#x2009;-&#x2009;1.75), Delorme procedure (-&#x2009;13.10;&#x2009;-&#x2009;41.26,&#x2009;-&#x2009;2.09), resection rectopexy (-&#x2009;11.98;&#x2009;-&#x2009;41.36,&#x2009;-&#x2009;0.19), sponge rectopexy (-&#x2009;13.19;&#x2009;-&#x2009;42.87,&#x2009;-&#x2009;0.54), and sutured rectopexy (-&#x2009;13.12;&#x2009;-&#x2009;42.58,&#x2009;-&#x2009;1.50), but similar odds to ventral mesh rectopexy (-&#x2009;12.09;&#x2009;-&#x2009;41.7, 0.03). Differences among the procedures in complications, operation time, and improvement in FI were not significant.<br><br>CONCLUSIONS: Posterior mesh rectopexy ranked best with the lowest recurrence while perineal procedures ranked worst with the highest recurrence rates.}, }
@article {pmid37150613, year = {2023}, author = {Qasimi, MI and Fukuzawa, S and Suenaga, K and Kambe, J and Li, C and Tomonaga, S and Kawase, T and Tsukahara, T and Hirayama, K and Inoue, R and Yamamoto, Y and Nagaoka, K}, title = {L-amino acid oxidase-1 is involved in the gut-liver axis by regulating 5-aminolevulinic acid production in mice.}, journal = {The Journal of veterinary medical science}, volume = {85}, number = {6}, pages = {672-679}, pmid = {37150613}, issn = {1347-7439}, mesh = {Animals ; Mice ; *Aminolevulinic Acid/metabolism ; *L-Amino Acid Oxidase/genetics/metabolism ; Hydrogen Peroxide/metabolism ; Liver/metabolism ; Cytokines/metabolism ; RNA, Messenger/metabolism ; Mice, Inbred C57BL ; }, abstract = {L-amino acid oxidase (LAAO) is a metabolic enzyme that converts L-amino acids into ketoacids, ammonia, and hydrogen peroxide (H2O2). The generated H2O2 has previously been shown to have antibacterial and gut microbiota-modulatory properties in LAO1 knock-out (KO) mice. Since most microbial metabolites reach the liver through the portal vein, we examined gut-liver interactions in LAO1 KO mice. We found lower total cholesterol levels, higher glutamic pyruvic transaminase (GPT) levels in the serum, and higher pro-inflammatory cytokine mRNA expression in the liver tissue. In wild-type (WT) mice, LAO1 was expressed in gut tissues (ileum and colon). Microbiome analysis revealed that the abundance of some bacteria was altered in LAO1 KO mice. However, short-chain fatty acid (SCFAs) levels in cecal feces and gut permeability did not change. Fecal microbiota transplantation (FMT) revealed that feces from LAO1 KO mice slightly stimulated pro-inflammatory cytokine expression in the liver. During metabolomic analysis, 5-aminolevulinic acid (5-ALA) was the only metabolite found to be significantly upregulated in the portal and abdominal veins of the LAO1 KO mice. Intraperitoneal administration of 5-ALA to WT mice significantly increased IL-6 mRNA expression in the liver. These observations suggest that gut LAO1 plays a role in regulating 5-ALA production and that a high level of 5-ALA stimulates the liver to increase pro-inflammatory cytokine expression by disrupting LAO1 in mice.}, }
@article {pmid37150070, year = {2023}, author = {Chernova, VO and Terveer, EM and van Prehn, J and Kuijper, EJ and Keller, JJ and van der Meulen-de Jong, AE and Bauer, MP and van Hilten, JJ and Contarino, MF}, title = {Fecal microbiota transplantation for Parkinson's disease using levodopa - carbidopa intestinal gel percutaneous endoscopic gastro-jejeunal tube.}, journal = {Parkinsonism &amp; related disorders}, volume = {111}, number = {}, pages = {105410}, doi = {10.1016/j.parkreldis.2023.105410}, pmid = {37150070}, issn = {1873-5126}, mesh = {Humans ; *Levodopa/therapeutic use ; Carbidopa ; *Parkinson Disease/drug therapy ; Antiparkinson Agents/therapeutic use ; Fecal Microbiota Transplantation ; Gels/therapeutic use ; Drug Combinations ; }, abstract = {We report a patient with a 5-year diagnosis of akinetic-rigid Parkinson's disease under treatment with Levodopa-Carbidopa Intestinal Gel therapy through a PEG-J tube due to motor complications, in which, in the context of a clinical study, we successfully and safely administered fecal microbiota transplant through a PEG-J.}, }
@article {pmid37147692, year = {2023}, author = {An, Y and Dai, H and Duan, Y and Cheng, L and Shi, L and He, C and Wang, C and Lv, Y and Li, H and Zhang, H and Huang, Y and Fu, W and Sun, W and Zhao, B}, title = {The relationship between gut microbiota and susceptibility to type 2 diabetes mellitus in rats.}, journal = {Chinese medicine}, volume = {18}, number = {1}, pages = {49}, pmid = {37147692}, issn = {1749-8546}, support = {81973535//National Natural Science Foundation of China/ ; }, abstract = {PURPOSE: The purpose of this study is to investigate the relationship between the susceptibility to type 2 diabetes and gut microbiota in rats and to explore the potential mechanism involved.<br><br>METHODS: Thirty-two SPF-grade SD rats were raised as donor rats, and divided into control, type 2 diabetes mellitus (T2DM, fasting blood glucose&#x2009;&#x2265;&#x2009;11.1&#xa0;mmol/L), and Non-T2DM (fasting blood glucose&#x2009;<&#x2009;11.1&#xa0;mmol/L) groups. Feces were collected and prepared as fecal bacteria supernatants Diab (fecal bacteria supernatant of T2DM group rats), Non (fecal bacteria supernatant of Non-T2DM group rats), and Con (fecal bacteria supernatant of control group rats). Another seventy-nine SPF-grade SD rats were separated into normal saline (NS) and antibiotics (ABX) groups and given normal saline and antibiotics solutions, respectively. In addition, the ABX group rats were randomly separated into ABX-ord (fed with a 4-week ordinary diet), ABX-fat (fed with a 4-week high-fat diet and STZ ip), FMT-Diab (with transplanted fecal bacteria supernatant Diab and fed with a 4-week high-fat diet and STZ ip), FMT-Non (with transplanted fecal bacteria supernatant Non and fed with a 4-week high-fat diet and STZ ip), and FMT-Con (with transplanted fecal bacteria supernatant Con and fed with a 4-week high-fat diet and STZ ip) groups. Furthermore, the NS group was randomly divided into NS-ord (fed with a 4-week ordinary diet) and NS-fat (fed with a 4-week high-fat diet and STZ ip) groups. After this, the short-chain fatty acids (SCFAs) in the feces were detected using gas chromatography, and the gut microbiota were detected using 16S rRNA gene sequencing. Finally, G protein-coupled receptor 41 (GPR41) and GPR43 were detected by western blot and quantitative real-time polymerase chain reaction.<br><br>RESULTS: G__Ruminococcus_gnavus_group were more abundant in the FMT-Diab group compared to the ABX-fat and FMT-Non groups. The levels of blood glucose, serum insulin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were also higher in the FMT-Diab group compared to those of the ABX-fat group. Compared to the ABX-fat group, both the FMT-Diab and FMT-Non groups had higher contents of acetic and butyric acid, and the expression of GPR41/43 were significantly higher as well.<br><br>CONCLUSIONS: G__Ruminococcus_gnavus_group might make rats more susceptible to T2DM; T2DM-susceptible flora transplantation increased the susceptibility to T2DM in rats. Additionally, gut microbiota-SCFAs-GPR41/43 may play a role in the development of T2DM. Lowering blood glucose by regulating gut microbiota may therefore become a new strategy for the treatment of T2DM in humans.}, }
@article {pmid37147641, year = {2023}, author = {Zhang, Y and Liu, L and Wei, C and Wang, X and Li, R and Xu, X and Zhang, Y and Geng, G and Dang, K and Ming, Z and Tao, X and Xu, H and Yan, X and Zhang, J and Hu, J and Li, Y}, title = {Vitamin K2 supplementation improves impaired glycemic homeostasis and insulin sensitivity for type 2 diabetes through gut microbiome and fecal metabolites.}, journal = {BMC medicine}, volume = {21}, number = {1}, pages = {174}, pmid = {37147641}, issn = {1741-7015}, mesh = {Mice ; Animals ; Humans ; *Gastrointestinal Microbiome ; *Insulin Resistance ; Vitamin K 2 ; *Diabetes Mellitus, Type 2 ; RNA, Ribosomal, 16S ; Feces ; Glucose/metabolism ; Obesity ; Dietary Supplements ; Homeostasis ; }, abstract = {BACKGROUND: There is insufficient evidence for the ability of vitamin K2 to improve type 2 diabetes mellitus symptoms by regulating gut microbial composition. Herein, we aimed to demonstrate the key role of the gut microbiota in the improvement of impaired glycemic homeostasis and insulin sensitivity by vitamin K2 intervention.<br><br>METHODS: We first performed a 6-month RCT on 60 T2DM participants with or without MK-7 (a natural form of vitamin K2) intervention. In addition, we conducted a transplantation of the MK-7-regulated microbiota in diet-induced obesity mice for 4&#xa0;weeks. 16S rRNA sequencing, fecal metabolomics, and transcriptomics in both study phases were used to clarify the potential mechanism.<br><br>RESULTS: After MK-7 intervention, we observed notable 13.4%, 28.3%, and 7.4% reductions in fasting serum glucose (P&#x2009;=&#x2009;0.048), insulin (P&#x2009;=&#x2009;0.005), and HbA1c levels (P&#x2009;=&#x2009;0.019) in type 2 diabetes participants and significant glucose tolerance improvement in diet-induced obesity mice (P&#x2009;=&#x2009;0.005). Moreover, increased concentrations of secondary bile acids (lithocholic and taurodeoxycholic acid) and short-chain fatty acids (acetic acid, butyric acid, and valeric acid) were found in human and mouse feces accompanied by an increased abundance of the genera that are responsible for the biosynthesis of these metabolites. Finally, we found that 4&#xa0;weeks of fecal microbiota transplantation significantly improved glucose tolerance in diet-induced obesity mice by activating colon bile acid receptors, improving host immune-inflammatory responses, and increasing circulating GLP-1 concentrations.<br><br>CONCLUSIONS: Our gut-derived findings provide evidence for a regulatory role of vitamin K2 on glycemic homeostasis, which may further facilitate the clinical implementation of vitamin K2 intervention for diabetes management.<br><br>TRIAL REGISTRATION: The study was registered at https://www.chictr.org.cn (ChiCTR1800019663).}, }
@article {pmid37146560, year = {2023}, author = {Kani, K and Kasai, K and Tada, Y and Ishibashi, R and Takano, S and Igarashi, N and Ichimura-Shimizu, M and Tsuneyama, K and Furusawa, Y and Nagai, Y}, title = {The innate immune receptor RP105 promotes metabolic syndrome by altering gut microbiota composition and intestinal barrier function.}, journal = {Biochemical and biophysical research communications}, volume = {664}, number = {}, pages = {77-85}, doi = {10.1016/j.bbrc.2023.04.068}, pmid = {37146560}, issn = {1090-2104}, mesh = {Animals ; Mice ; *Metabolic Syndrome ; Obesity/metabolism ; *Gastrointestinal Microbiome/physiology ; RNA, Ribosomal, 16S/genetics ; Diet, High-Fat/adverse effects ; Weight Gain ; Immunity, Innate ; Mice, Inbred C57BL ; }, abstract = {Radioprotective 105 (RP105) plays a key role in the development of high-fat diet (HFD)-induced metabolic disorders; however, the underlying mechanisms remain to be understood. Here, we aimed to uncover whether RP105 affects metabolic syndrome through the modification of gut microbiota. We confirmed that body weight gain and fat accumulation by HFD feeding were suppressed in Rp105[-/-] mice. Fecal microbiome transplantation from HFD-fed donor Rp105[-/-] mice into HFD-fed recipient wild-type mice significantly improved various abnormalities associated with metabolic syndrome, including body weight gain, insulin resistance, hepatic steatosis, macrophage infiltration and inflammation in the adipose tissue. In addition, HFD-induced intestinal barrier dysfunction was attenuated by fecal microbiome transplantation from HFD-fed donor Rp105[-/-] mice. A 16S rRNA sequence analysis indicated that RP105 modified gut microbiota composition and was involved in the maintenance of its diversity. Thus, RP105 promotes metabolic syndrome by altering gut microbiota composition and intestinal barrier function.}, }
@article {pmid37145345, year = {2023}, author = {Sha, H and He, X and Yan, K and Li, J and Li, X and Xie, Y and Yang, Y and Deng, Y and Li, G and Yang, J}, title = {Blocking coprophagy increases the levels of inflammation and depression in healthy mice as well as mice receiving fecal microbiota transplantation from disease model mice donors.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {131}, number = {7}, pages = {351-368}, doi = {10.1111/apm.13326}, pmid = {37145345}, issn = {1600-0463}, mesh = {Mice ; Animals ; *Fecal Microbiota Transplantation ; *Depression/psychology ; Coprophagia ; Inflammation ; Feces ; Cytokines/metabolism ; }, abstract = {Rodents have been extensively used as animal models in microbiome studies. However, all rodents have a habitual nature called coprophagy, a phenomenon that they self-reinoculate feces into their gastrointestinal tract. Recent studies have shown that blocking coprophagy can alter rodents' diversity of gut microbiota, metabolism, neurochemistry, and cognitive behavior. However, whether rodents' coprophagy behavior affects the levels of inflammation and depression is unclear. In order to address this problem, we first blocked coprophagy in healthy mice. It displayed an increase in the levels of depression, verified by depressive-like behaviors and mood-related indicators, and inflammation, verified by the increased levels of the pro-inflammatory cytokine, in coprophagy-blocked mice. Furthermore, we transplanted fecal microbiota from chronic restraint stress (CRS) depression model mice and lipopolysaccharide (LPS) inflammation model mice to healthy recipient mice, respectively. It showed that the disease-like phenotypes in the coprophagy-blocked group were worse than those in the coprophagy-unblocked group, including severer depressive symptoms and higher levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and IFN-γ) in serum, prefrontal cortex (PFC), and hippocampus (HIP). These findings showed that blocking coprophagy in mice not only increased the levels of inflammation and depression in healthy mice but also aggravated inflammation and depression induced by fecal microbiota from disease donors. The discovery may provide a vital reference for future research involving FMT in rodents.}, }
@article {pmid37145326, year = {2023}, author = {Sha, S and Zeng, H and Gao, H and Shi, H and Quan, X and Chen, F and Liu, M and Xu, B and Liu, X}, title = {Adherent-invasive Escherichia coli LF82 aggravated intestinal inflammation in colitis mice by affecting the gut microbiota and Th17/Treg cell differentiation balance.}, journal = {Archives of microbiology}, volume = {205}, number = {6}, pages = {218}, pmid = {37145326}, issn = {1432-072X}, support = {2021JQ-420 and 2022SF-195//the youth program of Shaanxi Natural Science Foundation/ ; 2021JQ-420 and 2022SF-195//the youth program of Shaanxi Natural Science Foundation/ ; 2021JQ-420 and 2022SF-195//the youth program of Shaanxi Natural Science Foundation/ ; 2021JQ-420 and 2022SF-195//the youth program of Shaanxi Natural Science Foundation/ ; 2021JQ-420 and 2022SF-195//the youth program of Shaanxi Natural Science Foundation/ ; 2021JQ-420 and 2022SF-195//the youth program of Shaanxi Natural Science Foundation/ ; 2021JQ-420 and 2022SF-195//the youth program of Shaanxi Natural Science Foundation/ ; 3502Z20209156//the medical and health guidance project of Xiamen/ ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Escherichia coli ; T-Lymphocytes, Regulatory/metabolism/pathology ; *Colitis/metabolism/microbiology/pathology ; *Escherichia coli Infections/microbiology ; Bacteria ; Inflammation ; Cell Differentiation ; }, abstract = {The imbalance of Th17 and Treg cell differentiation, intestinal flora imbalance, and intestinal mucosal barrier damage may be important links in the occurrence and development of inflammatory bowel disease (IBD) since Th17 and Treg differentiation are affected by the intestinal flora. This study aimed to explore the effect of Escherichia coli (E. coli) LF82 on the differentiation of Th17 and Treg cells and the role of the intestinal flora in mouse colitis. The effects of E. coli LF82 infection on intestinal inflammation were evaluated by analyzing the disease activity index, histology, myeloperoxidase activity, FITC-D fluorescence value, and claudin-1 and ZO-1 expression. The effects of E. coli LF82 on the Th17/Treg balance and intestinal flora were analyzed by flow cytometry and 16S rDNA sequencing. Inflammatory markers, changes in the intestinal flora, and Th17/Treg cells were then detected after transplanting fecal bacteria from normal mice into colitis mice infected by E. coli LF82. We found that E. coli LF82 infection can aggravate the intestinal inflammation of mice colitis, destroy their intestinal mucosal barrier, increase intestinal mucosal permeability, and aggravate the imbalance of Th17/Treg differentiation and the disorder of intestinal flora. After improving the intestinal flora imbalance by fecal bacteria transplantation, intestinal inflammation and intestinal mucosal barrier damage were reduced, and the differentiation balance of Th17 and Treg cells was restored. This study showed that E. coli LF82 infection aggravates intestinal inflammation and intestinal mucosal barrier damage in colitis by affecting the intestinal flora composition and indirectly regulating the Th17 and Treg cell differentiation balance.}, }
@article {pmid37143538, year = {2023}, author = {Yu, H and Li, XX and Han, X and Chen, BX and Zhang, XH and Gao, S and Xu, DQ and Wang, Y and Gao, ZK and Yu, L and Zhu, SL and Yao, LC and Liu, GR and Liu, SL and Mu, XQ}, title = {Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1126808}, pmid = {37143538}, issn = {1664-302X}, abstract = {Many lines of evidence demonstrate the associations of colorectal cancer (CRC) with intestinal microbial dysbiosis. Recent reports have suggested that maintaining the homeostasis of microbiota and host might be beneficial to CRC patients, but the underlying mechanisms remain unclear. In this study, we established a CRC mouse model of microbial dysbiosis and evaluated the effects of fecal microbiota transplantation (FMT) on CRC progression. Azomethane and dextran sodium sulfate were used to induce CRC and microbial dysbiosis in mice. Intestinal microbes from healthy mice were transferred to CRC mice by enema. The vastly disordered gut microbiota of CRC mice was largely reversed by FMT. Intestinal microbiota from normal mice effectively suppressed cancer progression as assessed by measuring the diameter and number of cancerous foci and significantly prolonged survival of the CRC mice. In the intestine of mice that had received FMT, there were massive infiltration of immune cells, including CD8[+] T and CD49b[+] NK, which is able to directly kill cancer cells. Moreover, the accumulation of immunosuppressive cells, Foxp3[+] Treg cells, seen in the CRC mice was much reduced after FMT. Additionally, FMT regulated the expressions of inflammatory cytokines in CRC mice, including down-regulation of IL1a, IL6, IL12a, IL12b, IL17a, and elevation of IL10. These cytokines were positively correlated with Azospirillum_sp._47_25, Clostridium_sensu_stricto_1, the E. coli complex, Akkermansia, Turicibacter, and negatively correlated with Muribaculum, Anaeroplasma, Candidatus_Arthromitus, and Candidatus Saccharimonas. Furthermore, the repressed expressions of TGFb, STAT3 and elevated expressions of TNFa, IFNg, CXCR4 together promoted the anti-cancer efficacy. Their expressions were positively correlated with Odoribacter, Lachnospiraceae-UCG-006, Desulfovibrio, and negatively correlated with Alloprevotella, Ruminococcaceae UCG-014, Ruminiclostridium, Prevotellaceae UCG-001 and Oscillibacter. Our studies indicate that FMT inhibits the development of CRC by reversing gut microbial disorder, ameliorating excessive intestinal inflammation and cooperating with anti-cancer immune responses.}, }
@article {pmid37143119, year = {2023}, author = {Li, S and Zheng, J and He, J and Liu, H and Huang, Y and Huang, L and Wang, K and Zhao, X and Feng, B and Che, L and Fang, Z and Li, J and Xu, S and Lin, Y and Jiang, X and Hua, L and Zhuo, Y and Wu, D}, title = {Dietary fiber during gestation improves lactational feed intake of sows by modulating gut microbiota.}, journal = {Journal of animal science and biotechnology}, volume = {14}, number = {1}, pages = {65}, pmid = {37143119}, issn = {1674-9782}, support = {2023NSFSC0010//National Science Foundation of Sichuan Province/ ; 32230102//National Natural Science Foundation of China/ ; No.2021ZDZX0009//Major Scientific and Technological Special Project of Sichuan Province/ ; scsztd-2023-08-03//National Modern Agricultural Industry Technology System Sichuan Pig innovation team/ ; }, abstract = {BACKGROUND: The feed intake of sows during lactation is often lower than their needs. High-fiber feed is usually used during gestation to increase the voluntary feed intake of sows during lactation. However, the mechanism underlying the effect of bulky diets on the appetites of sows during lactation have not been fully clarified. The current study was conducted to determine whether a high-fiber diet during gestation improves lactational feed intake (LFI) of sows by modulating gut microbiota.<br><br>METHODS: We selected an appropriate high-fiber diet during gestation and utilized the fecal microbial transplantation (FMT) method to conduct research on the role of the gut microbiota in feed intake regulation of sows during lactation, as follows: high-fiber (HF) diet during gestation (n&#x2009;=&#x2009;23), low-fiber (LF) diet during gestation (n&#x2009;=&#x2009;23), and low-fiber diet&#x2009;+&#x2009;HF-FMT (LFM) during gestation (n&#x2009;=&#x2009;23).<br><br>RESULTS: Compared with the LF, sows in the HF and LFM groups had a higher LFI, while the sows also had higher peptide tyrosine tyrosine and glucagon-like peptide 1 on d 110 of gestation (G110 d). The litter weight gain of piglets during lactation and weaning weight of piglets from LFM group were higher than LF group. Sows given a HF diet had lower Proteobacteria, especially Escherichia-Shigella, on G110 d and higher Lactobacillus, especially Lactobacillus_mucosae_LM1 and Lactobacillus_amylovorus, on d 7 of lactation (L7 d). The abundance of Escherichia-Shigella was reduced by HF-FMT in numerically compared with the LF. In addition, HF and HF-FMT both decreased the perinatal concentrations of proinflammatory factors, such as endotoxin (ET), lipocalin-2 (LCN-2), tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), and interleukin-1&#x3b2; (IL-1&#x3b2;). The concentration of ET and LCN-2 and the abundance of Proteobacteria and Escherichia-Shigella were negatively correlated with the LFI of sows.<br><br>CONCLUSION: The high abundance of Proteobacteria, especially Escherichia-Shigella of LF sows in late gestation, led to increased endotoxin levels, which result in inflammatory responses and adverse effects on the LFI of sows. Adding HF during gestation reverses this process by increasing the abundance of Lactobacillus, especially Lactobacillus_mucosae_LM1 and Lactobacillus_amylovorus.}, }
@article {pmid37142392, year = {2024}, author = {Ng, RW and Dharmaratne, P and Wong, S and Hawkey, P and Chan, P and Ip, M}, title = {Revisiting the donor screening protocol of faecal microbiota transplantation (FMT): a systematic review.}, journal = {Gut}, volume = {73}, number = {6}, pages = {1029-1031}, pmid = {37142392}, issn = {1468-3288}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Donor Selection/methods ; Gastrointestinal Microbiome ; Systematic Reviews as Topic ; }, }
@article {pmid37138170, year = {2023}, author = {Zhou, S and Yu, J}, title = {Crohn's disease and breast cancer: a literature review of the mechanisms and treatment.}, journal = {Internal and emergency medicine}, volume = {18}, number = {5}, pages = {1303-1316}, pmid = {37138170}, issn = {1970-9366}, support = {No. Z-2017-24-2110//the Nutrition Clinical Research Foundation of China Foundation/ ; }, mesh = {Humans ; Female ; *Crohn Disease ; NF-kappa B ; *Breast Neoplasms/therapy ; Intestinal Mucosa/metabolism/pathology ; Neoplasm Recurrence, Local/metabolism/pathology ; Inflammation ; }, abstract = {This is a literature review describes Crohn's disease (CD) concomitant with breast cancer and summarizes possible common pathogenic mechanisms shared by the two diseases involving the IL-17 and NF-κB signaling pathways. Inflammatory cytokines including TNF-α and Th17 cells in CD patients can induce activation of the ERK1/2, NF-κB and Bcl-2 pathways. Hub genes are involved in the generation of cancer stem cells (CSCs) and are related to inflammatory mediators, including CXCL8, IL1-β and PTGS2, which promote inflammation and breast cancer growth, metastasis, and development. CD activity is highly associated with altered intestinal microbiota processes, including secretion of complex glucose polysaccharides by Ruminococcus gnavus colonies; furthermore, γ-proteobacteria and Clostridium are associated with CD recurrence and active CD, while Ruminococcaceae, Faecococcus and Vibrio desulfuris are associated with CD remission. Intestinal microbiota disorder promotes breast cancer occurrence and development. Bacteroides fragilis can produce toxins that induce breast epithelial hyperplasia and breast cancer growth and metastasis. Gut microbiota regulation can also improve chemotherapy and immunotherapy efficacy in breast cancer treatment. Intestinal inflammation can affects the brain through the brain-gut axis, which activates the hypothalamic‒pituitary‒adrenal (HPA) axis to induce anxiety and depression in patients; these effects can inhibit the antitumor immune responses of the immune system and promote breast cancer occurrence in patients with CD. There are few studies on the treatment of patients with CD concomitant with breast cancer, but published studies show three main strategies: new biological agents combined with breast cancer treatment methods, intestinal fecal bacteria transplantation, and dietary treatment.}, }
@article {pmid37138075, year = {2023}, author = {Park, JS and Gazzaniga, FS and Wu, M and Luthens, AK and Gillis, J and Zheng, W and LaFleur, MW and Johnson, SB and Morad, G and Park, EM and Zhou, Y and Watowich, SS and Wargo, JA and Freeman, GJ and Kasper, DL and Sharpe, AH}, title = {Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance.}, journal = {Nature}, volume = {617}, number = {7960}, pages = {377-385}, pmid = {37138075}, issn = {1476-4687}, support = {F32 CA260769/CA/NCI NIH HHS/United States ; T32 HD055148/HD/NICHD NIH HHS/United States ; P01 AI056299/AI/NIAID NIH HHS/United States ; P50 CA206963/CA/NCI NIH HHS/United States ; F32 CA247072/CA/NCI NIH HHS/United States ; K22 CA258960/CA/NCI NIH HHS/United States ; 1F32CA260769-01/CA/NCI NIH HHS/United States ; P50 CA101942/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Cell Adhesion Molecules, Neuronal ; Disease Models, Animal ; Down-Regulation ; *Drug Resistance, Neoplasm/drug effects ; Fecal Microbiota Transplantation ; Germ-Free Life ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; *Immunotherapy ; *Melanoma/immunology/microbiology/therapy ; *Microbiota ; Protein Binding/drug effects ; T-Lymphocytes/drug effects/immunology ; }, abstract = {The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been identified in mice[1-6]. Moreover, transplantation of faecal specimens from responders can improve the efficacy of anti-PD-1 therapy in patients with melanoma[7,8]. However, the increased efficacy from faecal transplants is variable and how gut bacteria promote anti-tumour immunity remains unclear. Here we show that the gut microbiome downregulates PD-L2 expression and its binding partner repulsive guidance molecule b (RGMb) to promote anti-tumour immunity and identify bacterial species that mediate this effect. PD-L1 and PD-L2 share PD-1 as a binding partner, but PD-L2 can also bind RGMb. We demonstrate that blockade of PD-L2-RGMb interactions can overcome microbiome-dependent resistance to PD-1 pathway inhibitors. Antibody-mediated blockade of the PD-L2-RGMb pathway or conditional deletion of RGMb in T cells combined with an anti-PD-1 or anti-PD-L1 antibody promotes anti-tumour responses in multiple mouse tumour models that do not respond to anti-PD-1 or anti-PD-L1 alone (germ-free mice, antibiotic-treated mice and even mice colonized with stool samples from a patient who did not respond to treatment). These studies identify downregulation of the PD-L2-RGMb pathway as a specific mechanism by which the gut microbiota can promote responses to PD-1 checkpoint blockade. The results also define a potentially effective immunological strategy for treating patients who do not respond to PD-1 cancer immunotherapy.}, }
@article {pmid37132118, year = {2023}, author = {Okamura, T and Hamaguchi, M and Nakajima, H and Kitagawa, N and Majima, S and Senmaru, T and Okada, H and Ushigome, E and Nakanishi, N and Sasano, R and Fukui, M}, title = {Milk protects against sarcopenic obesity due to increase in the genus Akkermansia in faeces of db/db mice.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {14}, number = {3}, pages = {1395-1409}, pmid = {37132118}, issn = {2190-6009}, mesh = {Animals ; Male ; Mice ; Akkermansia ; *Diabetes Mellitus, Type 2 ; Feces ; Milk ; Obesity/complications ; RNA, Ribosomal, 16S ; *Sarcopenia/prevention &amp; control ; }, abstract = {BACKGROUND: Sarcopenic obesity, a combination of sarcopenia and obesity, is a pathological feature of type 2 diabetes. Several human studies have shown that milk is useful in the prevention of sarcopenia. This study was aimed at clarifying the effect of milk on the prevention of sarcopenic obesity in db/db mice.<br><br>METHODS: A randomized and investigator-blinded study was conducted using male db/db mice. Eight-week-old db/db mice were housed for 8&#xa0;weeks and fed milk (100&#xa0;&#x3bc;L/day) using a sonde. The faecal microbiota transplantation (FMT) group received antibiotics for 2&#xa0;weeks, starting at 6&#xa0;weeks of age, followed by FMT twice a week until 16&#xa0;weeks of age.<br><br>RESULTS: Milk administration to db/db mice increased grip strength (Milk-: 164.2&#xa0;&#xb1;&#xa0;4.7&#xa0;g, Milk+: 230.2&#xa0;&#xb1;&#xa0;56.0&#xa0;g, P&#xa0;=&#xa0;0.017), muscle mass (soleus muscle, Milk-: 164.2&#xa0;&#xb1;&#xa0;4.7&#xa0;mg, Milk+: 230.2&#xa0;&#xb1;&#xa0;56.0&#xa0;mg, P&#xa0;<&#xa0;0.001; plantaris muscle, Milk-: 13.3&#xa0;&#xb1;&#xa0;1.2&#xa0;mg, Milk+: 16.0&#xa0;&#xb1;&#xa0;1.7&#xa0;mg, P&#xa0;<&#xa0;0.001) and decreased visceral fat mass (Milk-: 2.39&#xa0;&#xb1;&#xa0;0.08&#xa0;g, Milk+: 1.98&#xa0;&#xb1;&#xa0;0.04&#xa0;mg, P&#xa0;<&#xa0;0.001), resulting in a significant increase in physical activity (light: P&#xa0;=&#xa0;0.013, dark: P&#xa0;=&#xa0;0.034). FMT from mice fed milk not only improved sarcopenic obesity but also significantly improved glucose intolerance. Microarray analysis of gene expression in the small intestine revealed that the expression of amino acid absorption transporter genes, namely, SIc7a5 (P&#xa0;=&#xa0;0.010), SIc7a1 (P&#xa0;=&#xa0;0.015), Ppp1r15a (P&#xa0;=&#xa0;0.041) and SIc7a11 (P&#xa0;=&#xa0;0.029), was elevated in mice fed milk. In 16S rRNA sequencing of gut microbiota, the genus Akkermansia was increased in both the mice fed milk and the FMT group from the mice fed milk.<br><br>CONCLUSIONS: The findings of this study suggest that besides increasing the intake of nutrients, such as amino acids, milk consumption also changes the intestinal environment, which might contribute to the mechanism of milk-induced improvement of sarcopenic obesity.}, }
@article {pmid37130682, year = {2023}, author = {Dougé, A and Ravinet, A and Corriger, A and Cabrespine, A and Wasiak, M and Pereira, B and Sokol, H and Nguyen, S and Bay, JO}, title = {Faecal microbiota transplantation to prevent complications after allogeneic stem cell transplantation for haematological malignancies: a study protocol for a randomised controlled phase-II trial (the FMT-allo study).}, journal = {BMJ open}, volume = {13}, number = {5}, pages = {e068480}, pmid = {37130682}, issn = {2044-6055}, mesh = {Humans ; Male ; Female ; Fecal Microbiota Transplantation/adverse effects ; Prospective Studies ; Neoplasm Recurrence, Local/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Graft vs Host Disease/prevention &amp; control/etiology ; *Hematologic Neoplasms/therapy ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; }, abstract = {INTRODUCTION: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) is a major treatment for many haematological malignancies. The procedure has a good success rate but high transplant-related toxicity (TRM). TRM is mostly related to graft-versus-host disease (GvHD) and infectious complications. Alterations of the intestinal microbiota plays a major role in the development of allo-HSCT complications. The gut microbiota could be restored by faecal microbiota transplantation (FMT). However, there are no published randomised studies assessing the efficacy of FMT for GvHD prophylaxis.<br><br>METHODS AND ANALYSIS: This prospective, open-label, multi-centre, parallel-group, randomised phase-II clinical trial has been designed to assess the effect of FMT on toxicity in patients treated with myeloablative allo-HSCT for haematological malignancy. Based on Fleming's single-stage sample size estimation procedure, the design plans to include 60 male and female patients aged 18 or over per arm, to be randomly assigned to two groups, one with and one without (control group) FMT. The primary endpoint is GvHD-free relapse-free survival rate at 1&#x2009;year after allo-HSCT. Secondary endpoints are outcome measures of the impact of FMT on allo-HSCT-related morbidity and mortality (overall survival and progression-free survival at 1 and 2 years, haematological parameters, infectious complications, tolerance and safety of FMT). The primary endpoint will be evaluated according to assumptions of the single-stage Fleming design, compared between groups by a log-rank test and further investigated in a multivariate marginal structural Cox model taking into account centre effect. The proportional-hazard hypothesis will be verified using Schoenfeld's test and by plotting residuals.<br><br>ETHICS AND DISSEMINATION: The local institutional review board (CPP Sud-Est II, France) issued approval on 27 January 2021. The French national authorities issued approval on 15 April 2021. The outcome of the study will be disseminated via peer-reviewed publications and at congresses.<br><br>TRIAL REGISTRATION NUMBER: NCT04935684.}, }
@article {pmid37125201, year = {2023}, author = {Xu, H and Xu, Z and Long, S and Li, Z and Jiang, J and Zhou, Q and Huang, X and Wu, X and Wei, W and Li, X}, title = {The role of the gut microbiome and its metabolites in cerebrovascular diseases.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1097148}, pmid = {37125201}, issn = {1664-302X}, abstract = {The gut microbiome is critically involved in maintaining normal physiological function in the host. Recent studies have revealed that alterations in the gut microbiome contribute to the development and progression of cerebrovascular disease via the microbiota-gut-brain axis (MGBA). As a broad communication network in the human body, MGBA has been demonstrated to have significant interactions with various factors, such as brain structure and function, nervous system diseases, etc. It is also believed that the species and composition of gut microbiota and its metabolites are intrinsically linked to vascular inflammation and immune responses. In fact, in fecal microbiota transplantation (FMT) research, specific gut microbiota and downstream-related metabolites have been proven to not only participate in various physiological processes of human body, but also affect the occurrence and development of cerebrovascular diseases directly or indirectly through systemic inflammatory immune response. Due to the high mortality and disability rate of cerebrovascular diseases, new treatments to improve intestinal dysbacteriosis have gradually attracted widespread attention to better ameliorate the poor prognosis of cerebrovascular diseases in a non-invasive way. This review summarizes the latest advances in the gut microbiome and cerebrovascular disease research and reveals the profound impact of gut microbiota dysbiosis and its metabolites on cerebrovascular diseases. At the same time, we elucidated molecular mechanisms whereby gut microbial metabolites regulate the expression of specific interleukins in inflammatory immune responses. Moreover, we further discuss the feasibility of novel therapeutic strategies targeting the gut microbiota to improve the outcome of patients with cerebrovascular diseases. Finally, we provide new insights for standardized diagnosis and treatment of cerebrovascular diseases.}, }
@article {pmid37125159, year = {2023}, author = {Kong, CY and Yang, YQ and Han, B and Chen, HL and Mao, YQ and Huang, JT and Wang, LS and Li, ZM}, title = {Fecal microbiome transplant from patients with lactation mastitis promotes mastitis in conventional lactating mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1123444}, pmid = {37125159}, issn = {1664-302X}, abstract = {INTRODUCTION: Lactation mastitis seriously severely affects the health of lactating females and their infants, yet the underlying causes of clinical lactation mastitis remain unclear.<br><br>METHODS: In this study, we used microbiota-humanized mice as a model to investigate the role of gut microbiota in lactation mastitis. We compared the fecal microbiota of lactation mastitis patients and healthy individuals and conducted fecal microbiota transplantation (FMT) experiments in an antibiotic-pretreated mouse model to test whether gut microbes contribute to human lactation mastitis.<br><br>RESULTS: Our results showed that gut microbiota diversity was reduced and dysbiosis was present in lactating mastitis patients. FMT from lactation mastitis patients (M-FMT), but not from healthy individuals (H-FMT), to antibiotic-treated mice resulted in lactation mastitis. The inflammation in mice caused by gut microbiota from lactating mastitis patients appears to be pervasive, as hepatocytes from mice that received feces from lactating mastitis patients showed marked swelling. In addition, serum pro-inflammatory factors, including IL-4, IL-17, MPO, IL-6, IL-1&#x3b2;, and TNF-&#x3b1;, were significantly increased in the M-FMT group. The Firmicutes/Bacteroidetes ratio (F/B), a biomarker of gut dysbiosis, was significantly increased in the M-FMT group. At the phylum level, Actinobacteria were significantly increased, and Verrucomicrobia were significantly decreased in the M-FMT group. At the genus level, Ruminococcus and Faecalibacterium were significantly reduced, while Parabacteroides were significantly increased in the feces of both patients with lactation mastitis and M-FMT mice. Moreover, our study revealed an "amplification effect" on microbiota differences and mastitis disease following human-to-mouse FMT.<br><br>CONCLUSION: Collectively, our findings demonstrate that the gut microbiota in lactating mastitis patients is dysbiotic and contributes to the pathogenesis of mastitis.}, }
@article {pmid37122756, year = {2023}, author = {Dong, Y and Zhang, K and Wei, J and Ding, Y and Wang, X and Hou, H and Wu, J and Liu, T and Wang, B and Cao, H}, title = {Gut microbiota-derived short-chain fatty acids regulate gastrointestinal tumor immunity: a novel therapeutic strategy?.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1158200}, pmid = {37122756}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; CD8-Positive T-Lymphocytes ; Fatty Acids, Volatile ; Butyrates/therapeutic use ; *Gastrointestinal Neoplasms/therapy ; Tumor Microenvironment ; }, abstract = {Tumor immune microenvironment (TIME), a tumor-derived immune component, is proven to be closely related to the development, metastasis, and recurrence of tumors. Gut microbiota and its fermented-metabolites short-chain fatty acids (SCFAs) play a critical role in maintaining the immune homeostasis of gastrointestinal tumors. Consisting mainly of acetate, propionate, and butyrate, SCFAs can interact with G protein-coupled receptors 43 of T helper 1 cell or restrain histone deacetylases (HDACs) of cytotoxic T lymphocytes to exert immunotherapy effects. Studies have shed light on SCFAs can mediate the differentiation and function of regulatory T cells, as well as cytokine production in TIME. Additionally, SCFAs can alter epigenetic modification of CD8[+] T cells by inhibiting HDACs to participate in the immune response process. In gastrointestinal tumors, the abundance of SCFAs and their producing bacteria is significantly reduced. Direct supplementation of dietary fiber and probiotics, or fecal microbiota transplantation to change the structure of gut microbiota can both increase the level of SCFAs and inhibit tumor development. The mechanism by which SCFAs modulate the progression of gastrointestinal tumors has been elucidated in this review, aiming to provide prospects for the development of novel immunotherapeutic strategies.}, }
@article {pmid37117118, year = {2023}, author = {Yang, R and Chen, Z and Cai, J}, title = {Fecal microbiota transplantation: Emerging applications in autoimmune diseases.}, journal = {Journal of autoimmunity}, volume = {141}, number = {}, pages = {103038}, doi = {10.1016/j.jaut.2023.103038}, pmid = {37117118}, issn = {1095-9157}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Microbiota ; *Inflammatory Bowel Diseases/therapy ; *Autoimmune Diseases/therapy ; Treatment Outcome ; }, abstract = {Both genetic susceptibility and environmental factors are important contributors to autoimmune disease pathogenesis. As an environmental factor, the gut microbiome plays a crucial role in the development and progression of autoimmune diseases. Thus, strategies targeting gut microbiome alterations can potentially be used to treat autoimmune disease. Microbiota-based interventions, such as prebiotics, probiotics, dietary interventions, and fecal microbiota transplantation (FMT), have attracted growing interest as novel treatment approaches. FMT is an effective method for treating recurrent Clostridioides difficile infections; moreover, it is emerging as a promising treatment for patients with inflammatory bowel disease and other autoimmune diseases. Although the mechanisms underpinning the interaction between the gut microbiome and host are not fully understood in patients with autoimmune disease, FMT has been shown to restore altered gut microbiota composition, rebuild the intestinal microecosystem, and mediate innate and adaptive immune responses to achieve a therapeutic effect. In this review, we provide an overview of FMT and discuss how FMT can be used as a novel treatment approach for autoimmune diseases. Furthermore, we discuss recent challenges and offer future research directions.}, }
@article {pmid37116852, year = {2023}, author = {Liu, Y and Chen, LJ and Li, XW and Yang, JZ and Liu, JL and Zhang, KK and Li, JH and Wang, Q and Xu, JT and Zhi, X}, title = {Gut microbiota contribute to Methamphetamine-induced cardiotoxicity in mouse model.}, journal = {Chemico-biological interactions}, volume = {379}, number = {}, pages = {110512}, doi = {10.1016/j.cbi.2023.110512}, pmid = {37116852}, issn = {1872-7786}, mesh = {Male ; Mice ; Animals ; *Methamphetamine/toxicity ; *Gastrointestinal Microbiome ; Cardiotoxicity ; Phosphatidylinositol 3-Kinases ; Anti-Bacterial Agents ; }, abstract = {Methamphetamine (METH) is a psychotropic drug known to cause cardiotoxicity. The gut-heart axis is emerging as an important pathway linking gut microbiota to cardiovascular disease, but the precise association between METH-induced cardiotoxicity and gut microbiota has yet to be elucidated. In this study, we established an escalating dose-multiple METH administration model in male BALB/c mice, examined cardiac injury and gut microbiota, and investigated the contribution of gut microbiota to cardiotoxicity induced by METH. Additionally, we treated mice with antibiotics and fecal microbiota transplantation (FMT) to assess the impact of gut microbiota on cardiotoxicity. Our results showed that METH exposure altered the p53 and PI3K/Akt signaling pathways and modulated the apoptosis pathway in heart tissue, accompanied by elevated levels of Bax/BCL-2 expression and cleaved caspase-3 proteins. METH exposure increased the diversity and richness of gut microbiota, and significantly changed the microbial community composition, accompanied by elevated abundance of Lactobacillus, Bifidobacterium, and decreased abundance of Bacteroides, norank_f_Muribaculaceae and Alistipes. Eliminating gut microbiota by antibiotics treatment alleviated METH-induced cardiotoxicity, while FMT treatment transferred similar cardiac injury manifestations from METH-exposed mice to healthy recipient mice. Our study unveils the crucial involvement of gut microbiota in the development of cardiotoxicity induced by METH and provides potential strategies for treating cardiac complications caused by METH.}, }
@article {pmid37114052, year = {2023}, author = {Schroeder, JH and Beattie, G and Lo, JW and Zabinski, T and Powell, N and Neves, JF and Jenner, RG and Lord, GM}, title = {CD90 is not constitutively expressed in functional innate lymphoid cells.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1113735}, pmid = {37114052}, issn = {1664-3224}, support = {MR/M003493/1/MRC_/Medical Research Council/United Kingdom ; MR/K002996/1/MRC_/Medical Research Council/United Kingdom ; MR/R024812/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; C7893/A26233/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; *Colitis/metabolism ; Cytokines/metabolism ; Dysbiosis/metabolism ; *Immunity, Innate ; Lymphocytes/metabolism ; Thy-1 Antigens/immunology ; }, abstract = {Huge progress has been made in understanding the biology of innate lymphoid cells (ILC) by adopting several well-known concepts in T cell biology. As such, flow cytometry gating strategies and markers, such as CD90, have been applied to indentify ILC. Here, we report that most non-NK intestinal ILC have a high expression of CD90 as expected, but surprisingly a sub-population of cells exhibit low or even no expression of this marker. CD90-negative and CD90-low CD127[+] ILC were present amongst all ILC subsets in the gut. The frequency of CD90-negative and CD90-low CD127[+] ILC was dependent on stimulatory cues in vitro and enhanced by dysbiosis in vivo. CD90-negative and CD90-low CD127[+] ILC were a potential source of IL-13, IFNγ and IL-17A at steady state and upon dysbiosis- and dextran sulphate sodium-elicited colitis. Hence, this study reveals that, contrary to expectations, CD90 is not constitutively expressed by functional ILC in the gut.}, }
@article {pmid37970585, year = {2022}, author = {Drefs, M and Schardey, J and von Ehrlich-Treuenstätt, V and Wirth, U and Burian, M and Zimmermann, P and Werner, J and Kühn, F}, title = {Endoscopic Treatment Options for Gastrointestinal Leaks.}, journal = {Visceral medicine}, volume = {38}, number = {5}, pages = {311-321}, pmid = {37970585}, issn = {2297-4725}, abstract = {BACKGROUND: Spontaneous or postoperative gastrointestinal defects are still life-threatening complications with elevated morbidity and mortality. Recently, endoscopic treatment options - up and foremost endoscopic vacuum therapy (EVT) - have become increasingly popular and have shown promising results in these patients.<br><br>METHODS: We performed an electronic systematic search of the MEDLINE databases (PubMed, EMBASE, and Cochrane) and searched for studies evaluating endoscopic options for the treatment of esophageal and colorectal leakages and/or perforations until March 2022.<br><br>RESULTS: The closure rate of both esophageal and colorectal defects by EVT is high and even exceeds the results of surgical revision in parts. Out of all endoscopic treatment options, EVT shows most evidence and appears to have the highest therapeutic success rates. Furthermore, EVT for both indications had a low rate of serious complications without relevant in-hospital mortality. In selected patients, EVT can be applied without fecal diversion and transferred to an outpatient setting.<br><br>CONCLUSION: Despite multiple endoscopic treatment options, EVT is increasingly becoming the new gold standard in endoscopic treatment of extraperitoneal defects of the upper and lower GI tract with localized peritonitis or mediastinitis and without close proximity to major blood vessels. However, further prospective, comparative studies are needed to strengthen the current evidence.}, }
@article {pmid38046904, year = {2022}, author = {Park, JC and Im, SH}, title = {The gut-immune-brain axis in neurodevelopment and neurological disorders.}, journal = {Microbiome research reports}, volume = {1}, number = {4}, pages = {23}, pmid = {38046904}, issn = {2771-5965}, abstract = {The gut-brain axis is gaining momentum as an interdisciplinary field addressing how intestinal microbes influence the central nervous system (CNS). Studies using powerful tools, including germ-free, antibiotic-fed, and fecal microbiota transplanted mice, demonstrate how gut microbiota perturbations alter the fate of neurodevelopment. Probiotics are also becoming more recognized as potentially effective therapeutic agents in alleviating symptoms of neurological disorders. While gut microbes may directly communicate with the CNS through their effector molecules, including metabolites, their influence on neuroimmune populations, including newly discovered brain-resident T cells, underscore the host immunity as a potent mediator of the gut-brain axis. In this review, we examine the unique immune populations within the brain, the effects of the gut microbiota on the CNS, and the efficacy of specific probiotic strains to propose the novel concept of the gut-immune-brain axis.}, }
@article {pmid38046357, year = {2022}, author = {Aguanno, D and Metwaly, A and Coleman, OI and Haller, D}, title = {Modeling microbiota-associated human diseases: from minimal models to complex systems.}, journal = {Microbiome research reports}, volume = {1}, number = {3}, pages = {17}, pmid = {38046357}, issn = {2771-5965}, abstract = {Alterations in the intestinal microbiota are associated with various human diseases of the digestive system, including obesity and its associated metabolic diseases, inflammatory bowel diseases (IBD), and colorectal cancer (CRC). All three diseases are characterized by modifications of the richness, composition, and metabolic functions of the human intestinal microbiota. Despite being multi-factorial diseases, studies in germ-free animal models have unarguably identified the intestinal microbiota as a causal driver of disease pathogenesis. However, for an increased mechanistic understanding of microbial signatures in human diseases, models require detailed refinement to closely mimic the human microbiota and reflect the complexity and range of dysbiosis observed in patients. The transplantation of human fecal microbiota into animal models represents a powerful tool for studying the causal and functional role of the dysbiotic human microbiome in a pathological context. While human microbiota-associated models were initially employed to study obesity, an increasing number of studies have applied this approach in the context of IBD and CRC over the past decade. In this review, we discuss different approaches that allow the functional validation of the bacterial contribution to human diseases, with emphasis on obesity and its associated metabolic diseases, IBD, and CRC. We discuss the utility of simple models, such as in vitro fermentation systems of the human microbiota and ex vivo intestinal organoids, as well as more complex whole organism models. Our focus here lies on human microbiota-associated mouse models in the context of all three diseases, as well as highlighting the advantages and limitations of this approach.}, }
@article {pmid38045643, year = {2022}, author = {Marasco, G and Cremon, C and Barbaro, MR and Stanghellini, V and Barbara, G}, title = {Gut microbiota signatures and modulation in irritable bowel syndrome.}, journal = {Microbiome research reports}, volume = {1}, number = {2}, pages = {11}, pmid = {38045643}, issn = {2771-5965}, abstract = {Irritable bowel syndrome (IBS) affects approximately one tenth of the general population and is characterized by abdominal pain associated with abnormalities in bowel habits. Visceral hypersensitivity, abnormal intestinal motor function, mucosal immune activation, and increased intestinal permeability concur to its pathophysiology. Psychological factors can influence symptom perception at the central nervous system level. In addition, recent evidence suggests that dysbiosis may be a key pathophysiological factor in patients with IBS. Increasing understanding of the pathophysiological mechanisms translates into new and more effective therapeutic approaches. Indeed, in line with this evidence, IBS therapies nowadays include agents able to modulate gut microbiota function and composition, such as diet, prebiotics, probiotics, and antibiotics. In addition, in the last decade, an increasing interest in fecal microbiota transplantation has been paid. An in-depth understanding of the intestinal microenvironment through accurate faucal microbiota and metabolite analysis may provide valuable insights into the pathophysiology of IBS, finally shaping new tailored IBS therapies.}, }
@article {pmid37600095, year = {2022}, author = {Freidin, D and Zilka, N and Horesh, N and Saukhat, O and Ram, E and Tejman-Yarden, S}, title = {Using Augmented Reality for Intraoperative Guidance During Sacral Neuromodulation System Implantation.}, journal = {Annals of surgery open : perspectives of surgical history, education, and clinical approaches}, volume = {3}, number = {1}, pages = {e138}, pmid = {37600095}, issn = {2691-3593}, abstract = {OBJECTIVE: The purpose of this study was to examine the feasibility of using augmented reality during lead placement for sacral nerve stimulation (SNS).<br><br>METHODS: The study was a prospective case series performed in a single tertiary center. Patients with fecal incontinence or urinary retention eligible for SNS according to the American society of colon and rectal surgeon's guidelines were included. Each patient underwent a computerized tomography scan of the sacrum and pelvic floor before surgery; and a segmentation of the sacral bone, the skin, and three fiducial markers on the lower back was produced. Surgical planning included the design of an ideal virtual transmission tract leading to the S3 foramen using the most suitable location and needle trajectory for introducing the lead. During the surgical intervention, a needle was inserted into the S3 foramen using the aligned tract as visualized using the Microsoft HoloLens first generation head mounted unit.<br><br>RESULTS: Overall, 11 patients were included. Mean operative time was 43.8 minutes (range 25-81 minutes). All patients reported a significant reduction from the preoperative level of the mean postoperative Cleveland Clinic Incontinence Score (CCIS) assessed 2 weeks after the temporary SNS implant (CCIS preoperative 13.3, postoperative 8.5; CI -7.35 to -2.25; P < 0.01). The surgeons reported the imaging useful, allowing accurate and easier approach.<br><br>CONCLUSIONS: Intraoperative augmented reality imaging for needle application during SNS appears to be feasible, practical, and may be useful in additional procedures.}, }
@article {pmid37117525, year = {2021}, author = {Mossad, O and Nent, E and Woltemate, S and Folschweiller, S and Buescher, JM and Schnepf, D and Erny, D and Staeheli, P and Bartos, M and Szalay, A and Stecher, B and Vital, M and Sauer, JF and Lämmermann, T and Prinz, M and Blank, T}, title = {Microbiota-dependent increase in δ-valerobetaine alters neuronal function and is responsible for age-related cognitive decline.}, journal = {Nature aging}, volume = {1}, number = {12}, pages = {1127-1136}, pmid = {37117525}, issn = {2662-8465}, mesh = {Animals ; Mice ; *Microbiota/physiology ; *Gastrointestinal Microbiome/physiology ; Cognition/physiology ; *Cognitive Dysfunction/metabolism ; Brain/metabolism ; }, abstract = {Understanding the physiological origins of age-related cognitive decline is of critical importance given the rising age of the world's population[1]. Previous work in animal models has established a strong link between cognitive performance and the microbiota[2-5], and it is known that the microbiome undergoes profound remodeling in older adults[6]. Despite growing evidence for the association between age-related cognitive decline and changes in the gut microbiome, the mechanisms underlying such interactions between the brain and the gut are poorly understood. Here, using fecal microbiota transplantation (FMT), we demonstrate that age-related remodeling of the gut microbiota leads to decline in cognitive function in mice and that this impairment can be rescued by transplantation of microbiota from young animals. Moreover, using a metabolomic approach, we found elevated concentrations of δ-valerobetaine, a gut microbiota-derived metabolite, in the blood and brain of aged mice and older adults. We then demonstrated that δ-valerobetaine is deleterious to learning and memory processes in mice. At the neuronal level, we showed that δ-valerobetaine modulates inhibitory synaptic transmission and neuronal network activity. Finally, we identified specific bacterial taxa that significantly correlate with δ-valerobetaine levels in the brain. Based on our findings, we propose that δ-valerobetaine contributes to microbiota-driven brain aging and that the associated mechanisms represent a promising target for countering age-related cognitive decline.}, }
@article {pmid37724079, year = {2021}, author = {Cheng, CK and Huang, Y}, title = {The gut-cardiovascular connection: new era for cardiovascular therapy.}, journal = {Medical review (2021)}, volume = {1}, number = {1}, pages = {23-46}, pmid = {37724079}, issn = {2749-9642}, abstract = {Our gut microbiome is constituted by trillions of microorganisms including bacteria, archaea and eukaryotic microbes. Nowadays, gut microbiome has been gradually recognized as a new organ system that systemically and biochemically interact with the host. Accumulating evidence suggests that the imbalanced gut microbiome contributes to the dysregulation of immune system and the disruption of cardiovascular homeostasis. Specific microbiome profiles and altered intestinal permeability are often observed in the pathophysiology of cardiovascular diseases. Gut-derived metabolites, toxins, peptides and immune cell-derived cytokines play pivotal roles in the induction of inflammation and the pathogenesis of dysfunction of heart and vasculature. Impaired crosstalk between gut microbiome and multiple organ systems, such as gut-vascular, heart-gut, gut-liver and brain-gut axes, are associated with higher cardiovascular risks. Medications and strategies that restore healthy gut microbiome might therefore represent novel therapeutic options to lower the incidence of cardiovascular and metabolic disorders.}, }
@article {pmid37117767, year = {2021}, author = {Boehme, M and Guzzetta, KE and Bastiaanssen, TFS and van de Wouw, M and Moloney, GM and Gual-Grau, A and Spichak, S and Olavarría-Ramírez, L and Fitzgerald, P and Morillas, E and Ritz, NL and Jaggar, M and Cowan, CSM and Crispie, F and Donoso, F and Halitzki, E and Neto, MC and Sichetti, M and Golubeva, AV and Fitzgerald, RS and Claesson, MJ and Cotter, PD and O'Leary, OF and Dinan, TG and Cryan, JF}, title = {Microbiota from young mice counteracts selective age-associated behavioral deficits.}, journal = {Nature aging}, volume = {1}, number = {8}, pages = {666-676}, pmid = {37117767}, issn = {2662-8465}, mesh = {Animals ; Mice ; *Microbiota ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Aging/genetics ; Brain ; }, abstract = {The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3-4 months) or old (19-20 months) donor mice into aged recipient mice (19-20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.}, }
@article {pmid37537802, year = {2015}, author = {Lee, EW and Lucioni, A and Lee, UJ and Kobashi, KC}, title = {National Practice Patterns of Infection Prophylaxis for Sacral Neuromodulation Device: A Survey of High Volume Providers.}, journal = {Urology practice}, volume = {2}, number = {1}, pages = {38-43}, doi = {10.1016/j.urpr.2014.07.003}, pmid = {37537802}, issn = {2352-0787}, abstract = {INTRODUCTION: Sacral neuromodulation using the InterStim® device is a safe, effective treatment for urgency, frequency, urgency incontinence, nonobstructive urinary retention and fecal incontinence. However, there is no standard recommendation regarding infection prophylaxis. Therefore, we surveyed the infection prophylaxis patterns of high volume device providers to describe current practice patterns of perioperative infection prophylaxis.<br><br>METHODS: A web based survey was sent to 35 high volume providers, including urologists, gynecologists and colorectal surgeons.<br><br>RESULTS: Our response rate was 89% (31 of 35 participants). Of the providers 51% were urologists, 39% were&#xa0;gynecologists and 10% were colorectal surgeons. Of the respondents 74% had performed more than 200&#xa0;procedures and 22% had done more than 500. The testing period was generally 1 to 2 weeks. Only 13% of the surveyed providers routinely screened for methicillin resistant Staphylococcus aureus. All providers administered antibiotics preoperatively, most commonly cefazolin or vancomycin, and 81% administered antibiotics postoperatively, most commonly cephalexin and trimethoprim-sulfamethoxazole. Most providers prescribed 5 to 7 days of treatment but 6 (19%) prescribed no postoperative antibiotics. In addition, 71% of respondents used adjunctive measures, frequently intraoperative wound irrigation and/or a preoperative chlorhexidine shower. After stages 1 and 2, 19% of providers prohibited showering for more than 3 days postoperatively while 61% permitted showering after 1 or 2 days and 19% recommended no bathing restriction.<br><br>CONCLUSIONS: We present the infection prevention practices of high volume InterStim sacral neuromodulation device implanters in the United States. Further study is warranted to guide evidence-based practice in InterStim infection prophylaxis.}, }
@article {pmid37113615, year = {2023}, author = {Lenti, MV and Scribano, ML and Biancone, L and Ciccocioppo, R and Pugliese, D and Pastorelli, L and Fiorino, G and Savarino, E and Caprioli, FA and Ardizzone, S and Fantini, MC and Tontini, GE and Orlando, A and Sampietro, GM and Sturniolo, GC and Monteleone, G and Vecchi, M and Kohn, A and Daperno, M and D'Incà, R and Corazza, GR and Di Sabatino, A}, title = {Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1031998}, pmid = {37113615}, issn = {2296-858X}, abstract = {Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice.}, }
@article {pmid37113132, year = {2023}, author = {Chen, X and Zhang, W and Lin, Z and Zheng, C and Chen, S and Zhou, H and Liu, Z}, title = {Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1103189}, pmid = {37113132}, issn = {2235-2988}, mesh = {Female ; Humans ; Activities of Daily Living ; *Cognitive Dysfunction/therapy/etiology ; *Fecal Microbiota Transplantation/adverse effects/methods ; Feces/microbiology ; Pilot Projects ; Treatment Outcome ; }, abstract = {BACKGROUND: Recent studies have reported that gut microbiota is closely associated with cognitive fuction. Fecal microbiota transplantation (FMT) may be a potential treatment for cognitive impairment, but its efficacy in patients with cognitive impairment is unknown.<br><br>OBJECTIVES: This study aimed to investigate the safety and efficacy of FMT for cognitive impairment treatment.<br><br>METHODS: Five patients aged 54-80 years (three women) were enrolled in this single-arm clinical trial from July 2021 to May 2022. The Montreal Cognitive Assessment-B (MoCA-B), Activities of Daily Living (ADL), and the cognitive section of the Alzheimer's Disease Assessment Scale (ADAS-Cog) were assessed at days 0, 30, 60, 90, and 180. Additionally, stool and serum samples were obtained twice before FMT was administered and six months after the treatment. The structure of fecal microbiota was analyzed by 16S RNA gene sequencing. Serum samples were analyzed for metabolomics and lipopolysaccharide (LPS)-binding proteins by liquid chromatography-mass spectrometry and enzyme-linked immunosorbent assay, respectively. Safety was assessed based on adverse events, vital signs, and laboratory parameters during FMT and the follow-up period.<br><br>RESULTS: The MoCA, ADL, and ADAS-Cog scores of patients with mild cognitive impairment (patients C and E) after FMT were improved or maintained compared with those before transplantation. However, patients with severe cognitive impairment (patients A, B, and D) had no worsening of cognitive scores. Fecal microbiota analysis showed that FMT changed the structure of gut microbiota. The results of serum metabolomics analysis suggested that there were significant changes in the serum metabolomics of patients after FMT, with 7 up-regulated and 28 down-regulated metabolites. 3b,12a-dihydroxy-5a-cholanoic acid, 25-acetylvulgaroside, deoxycholic acid, 2(R)-hydroxydocosanoic acid, and P-anisic acid increased, while bilirubin and other metabolites decreased. KEFF pathway analysis indicated that the main metabolic pathways were bile secretion and choline metabolism in cancer. No adverse effects were reported throughout the study.<br><br>CONCLUSIONS: In this pilot study, FMT could maintain and improve cognitive function in mild cognitive impairment by changing gut microbiota structure and affecting serum metabolomics. Fecal bacteria capsules were safe. However, further studies are needed to evaluate the safety and efficacy of fecal microbiota transplantation. ClinicalTrials.gov Identifier: CHiCTR2100043548.}, }
@article {pmid37111404, year = {2023}, author = {Sharma, M and Dhaliwal, M and Tyagi, R and Goyal, T and Sharma, S and Rawat, A}, title = {Microbiome and Its Dysbiosis in Inborn Errors of Immunity.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {37111404}, issn = {2076-0817}, abstract = {Inborn errors of immunity (IEI) can present with infections, autoimmunity, lymphoproliferation, granulomas, and malignancy. IEIs are due to genetic abnormalities that disrupt normal host-immune response or immune regulation. The microbiome appears essential for maintaining host immunity, especially in patients with a defective immune system. Altered gut microbiota in patients with IEI can lead to clinical symptoms. Microbial dysbiosis is the consequence of an increase in pro-inflammatory bacteria or a reduction in anti-inflammatory bacteria. However, functional and compositional differences in microbiota are also involved. Dysbiosis and a reduced alpha-diversity are well documented, particularly in conditions like common variable immunodeficiency. Deranged microbiota is also seen in Wiskott-Aldrich syndrome, severe combined immunodeficiency, chronic granulomatous disease, selective immunoglobulin-A deficiency, Hyper IgE syndrome (HIGES), X-linked lymphoproliferative disease-2, immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome, and defects of IL10 signalling. Distinct gastrointestinal, respiratory, and cutaneous symptoms linked to dysbiosis are seen in several IEIs, emphasizing the importance of microbiome identification. In this study, we discuss the processes that maintain immunological homeostasis between commensals and the host and the disruptions thereof in patients with IEIs. As the connection between microbiota, host immunity, and infectious illnesses is better understood, microbiota manipulation as a treatment strategy or infection prevention method would be more readily employed. Therefore, optimal prebiotics, probiotics, postbiotics, and fecal microbial transplantation can be promising strategies to restore the microbiota and decrease disease pathology in patients with IEIs.}, }
@article {pmid37111321, year = {2023}, author = {Kumar, A and Pramanik, J and Goyal, N and Chauhan, D and Sivamaruthi, BS and Prajapati, BG and Chaiyasut, C}, title = {Gut Microbiota in Anxiety and Depression: Unveiling the Relationships and Management Options.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {16}, number = {4}, pages = {}, pmid = {37111321}, issn = {1424-8247}, abstract = {The gut microbiota is critical for maintaining human health and the immunological system. Several neuroscientific studies have shown the significance of microbiota in developing brain systems. The gut microbiota and the brain are interconnected in a bidirectional relationship, as research on the microbiome-gut-brain axis shows. Significant evidence links anxiety and depression disorders to the community of microbes that live in the gastrointestinal system. Modified diet, fish and omega-3 fatty acid intake, macro- and micro-nutrient intake, prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, and 5-HTP regulation may all be utilized to alter the gut microbiota as a treatment approach. There are few preclinical and clinical research studies on the effectiveness and reliability of various therapeutic approaches for depression and anxiety. This article highlights relevant research on the association of gut microbiota with depression and anxiety and the different therapeutic possibilities of gut microbiota modification.}, }
@article {pmid37111173, year = {2023}, author = {Zhuang, H and Yang, Z and Chen, T and Jing, N and Zhou, Y and Jiang, G and Wang, Y and Wang, Z and Liu, Z}, title = {Boosting HSA Vaccination with Jujube Powder Modulating Gut Microbiota Favorable for Arginine Metabolism.}, journal = {Nutrients}, volume = {15}, number = {8}, pages = {}, pmid = {37111173}, issn = {2072-6643}, support = {2021Z99CFZ011//Chunfeng Foundation of Tsinghua University/ ; 20192000168//Xinjiang Tianhui Information Technology Co. Ltd./ ; 20172000941//Xinjiang Tianjianhemu Biotech Co. Ltd./ ; }, mesh = {Humans ; Animals ; Mice ; *Ziziphus ; Powders ; *Gastrointestinal Microbiome ; Serum Albumin, Human ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; Immunoglobulin G ; Vaccination ; Arginine/pharmacology ; }, abstract = {Whereas vaccination is established as one of the most effective and available methods against seasonal flu and holds high potential for many infectious diseases, immune response may differ among individuals and regions. In this study we examined the effects of gut microbiota on vaccination with human serum albumin (HSA) as the model vaccine in C57BL/6J mice. We observed that a two-week antibiotic cocktail (ABX) treatment hampered HSA-specific IgG1 in serum, whereas fecal microbiota transplantation (FMT) restored the gut microbiota impaired by the ABX treatment and consequently increased the proportions of macrophages in the mesenteric lymph nodes (MLNs), plasma cells in the peripheral blood, and HSA-specific immunoglobulin G1 (IgG1) in the serum. A week of daily application of jujube powder (800 mg/kg) to ABX-treated mice achieved a significantly higher HSA-specific IgG1 concentration in the serum compared with the ABX treatment group. Of particular note was that the administration of the jujube powder did not increase the myeloid cells, indicating a different mechanism of vaccination compared with FMT. More interestingly, daily pre-administration of jujube powder (800 mg/kg) to healthy mice one week ahead of vaccination boosted their immune response, as evidenced by the proportion of macrophages in the MLNs, B cells in the spleen, plasma cells and memory B cells in the peripheral blood, and HSA-specific IgG1 concentration in the serum. The 16S rRNA sequencing of gut microbiota revealed that the administration of jujube powder increased the abundance of Coriobacteriaceae associated with the metabolism of amino acids. The Kyoto encyclopedia of genes and genomes (KEGG) analysis suggested the altered microbiota is more favorable for arginine and proline metabolism, which may promote macrophages in the MLNs. These results indicate a high potential for boosting vaccination by manipulating gut microbiota with natural products.}, }
@article {pmid37110500, year = {2023}, author = {Dahiya, M and Jovel, J and Monaghan, T and Wong, K and Elhenawy, W and Chui, L and McAlister, F and Kao, D}, title = {In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {11}, number = {4}, pages = {}, pmid = {37110500}, issn = {2076-2607}, abstract = {IMPORTANCE: Although highly effective in treating recurrent Clostridioides difficile infection (RCDI), the mechanisms of action of fecal microbial transplantation (FMT) are not fully understood.<br><br>AIM: The aim of this study was to explore microbially derived products or pathways that could contribute to the therapeutic efficacy of FMT.<br><br>METHODS: Stool shotgun metagenomic sequencing data from 18 FMT-treated RCDI patients at 4 points in time were used for the taxonomic and functional profiling of their gut microbiome. The abundance of the KEGG orthology (KO) groups was subjected to univariate linear mixed models to assess the significance of the observed differences between 0 (pre-FMT), 1, 4, and 12 weeks after FMT.<br><br>RESULTS: Of the 59,987 KO groups identified by shotgun metagenomic sequencing, 27 demonstrated a statistically significant change after FMT. These KO groups are involved in many cellular processes, including iron homeostasis, glycerol metabolism, and arginine regulation, all of which have been implicated to play important roles in bacterial growth and virulence in addition to modulating the intestinal microbial composition.<br><br>CONCLUSION: Our findings suggest potential changes in key KO groups post-FMT, which may contribute to FMT efficacy beyond the restored microbial composition/diversity and metabolism of bile acids and short-chain fatty acids. Future larger studies that include a fecal metabolomics analysis combined with animal model validation work are required to further elucidate the molecular mechanisms.}, }
@article {pmid37107633, year = {2023}, author = {Benlabidi, S and Raddaoui, A and Lengliz, S and Cheriet, S and Hynds, P and Achour, W and Ghrairi, T and Abbassi, MS}, title = {Occurrence of High-Risk Clonal Lineages ST58, ST69, ST224, and ST410 among Extended-Spectrum β-Lactamase-Producing Escherichia coli Isolated from Healthy Free-Range Chickens (Gallus gallus domesticus) in a Rural Region in Tunisia.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, pmid = {37107633}, issn = {2073-4425}, mesh = {Animals ; *Escherichia coli ; *Chickens/genetics ; Multilocus Sequence Typing ; Tunisia/epidemiology ; beta-Lactamases/genetics ; Clone Cells ; }, abstract = {Antimicrobial-resistant Escherichia coli isolates have emerged in various ecologic compartments and evolved to spread globally. We sought to (1.) investigate the occurrence of ESBL-producing E. coli (ESBL-Ec) in feces from free-range chickens in a rural region and (2.) characterize the genetic background of antimicrobial resistance and the genetic relatedness of collected isolates. Ninety-five feces swabs from free-range chickens associated with two households (House 1/House 2) in a rural region in northern Tunisia were collected. Samples were screened to recover ESBL-Ec, and collected isolates were characterized for phenotype/genotype of antimicrobial resistance, integrons, and molecular typing (pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST)). Overall, 47 ESBL-Ec were identified, with the following genes detected: 35 blaCTX-M-1, 5 blaCTX-M-55, 5 blaCTX-M-15, 1 blaSHV-2, and 1 blaSHV-12. Resistance to fluoroquinolones, tetracycline, sulfonamides, and colistin was encoded by aac(6')-Ib-cr (n = 21), qnrB (n = 1), and qnrS (n = 2); tetA (n = 17)/tetB (n = 26); sul1 (n = 29)/sul2 (n = 18); and mcr-2 (n = 2) genes, respectively. PFGE and MLST identified genetic homogeneity of isolates in House 1; however, isolates from House 2 were heterogeneous. Notably, among nine identified sequence types, ST58, ST69, ST224, and ST410 belong to pandemic high-risk clonal lineages associated with extrapathogenic E. coli. Minor clones belonging to ST410 and ST471 were shared by chickens from both households. The virulence genes fyuA, fimH, papGIII, and iutA were detected in 35, 47, 17, and 23 isolates, respectively. Findings indicate a high occurrence of ESBL-Ec in free-range chickens and highlight the occurrence of pandemic zoonotic clones.}, }
@article {pmid37106510, year = {2023}, author = {Luo, X and Li, H and Fan, X and Wu, X and Zhou, R and Lei, Y and Xue, D and Yang, F and Xu, Y and Wang, K}, title = {The Gut Microbiota-Brain Axis: Potential Mechanism of Drug Addiction.}, journal = {Current topics in medicinal chemistry}, volume = {23}, number = {18}, pages = {1782-1792}, doi = {10.2174/1568026623666230418114133}, pmid = {37106510}, issn = {1873-4294}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Brain-Gut Axis ; *Microbiota ; Brain/metabolism ; *Nervous System Diseases/metabolism ; *Substance-Related Disorders ; }, abstract = {As a chronic encephalopathy, drug addiction is responsible for millions of deaths per year around the world. The gut microbiome is a crucial component of the human microbiome. Through dynamic bidirectional communication along the 'gut-brain axis,' gut bacteria cooperate with their hosts to regulate the development and function of the immune, metabolic, and nervous systems. These processes may affect human health because some brain diseases are related to the composition of gut bacteria, and disruptions in microbial communities have been implicated in neurological disorders. We review the compositional and functional diversity of the gut microbiome in drug addiction. We discuss intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems and possible contributions by the gut microbiota to neurological disorders. Finally, the treatment of probiotics and fecal transplantation was summarized. This was done to further understand the role of intestinal microecology in the pathogenesis of drug addiction and to explore new methods for the treatment of drug addiction.}, }
@article {pmid37106463, year = {2023}, author = {de Wouters d'Oplinter, A and Verce, M and Huwart, SJP and Lessard-Lord, J and Depommier, C and Van Hul, M and Desjardins, Y and Cani, PD and Everard, A}, title = {Obese-associated gut microbes and derived phenolic metabolite as mediators of excessive motivation for food reward.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {94}, pmid = {37106463}, issn = {2049-2618}, mesh = {Mice ; Animals ; *Motivation ; *Gastrointestinal Microbiome/physiology ; Obesity/metabolism ; Food ; Reward ; }, abstract = {BACKGROUND: Excessive hedonic consumption is one of the main drivers for weight gain. Identifying contributors of this dysregulation would help to tackle obesity. The gut microbiome is altered during obesity and regulates host metabolism including food intake.<br><br>RESULTS: By using fecal material transplantation (FMT) from lean or obese mice into recipient mice, we demonstrated that gut microbes play a role in the regulation of food reward (i.e., wanting and learning processes associated with hedonic food intake) and could be responsible for excessive motivation to obtain sucrose pellets and alterations in dopaminergic and opioid markers in reward-related brain areas. Through untargeted metabolomic approach, we identified the 3-(3'-hydroxyphenyl)propanoic acid (33HPP) as highly positively correlated with the motivation. By administrating 33HPP in mice, we revealed its effects on food reward.<br><br>CONCLUSIONS: Our data suggest that targeting the gut microbiota and its metabolites would be an interesting therapeutic strategy for compulsive eating, preventing inappropriate hedonic food intake. Video Abstract.}, }
@article {pmid37106038, year = {2024}, author = {Maghini, DG and Dvorak, M and Dahlen, A and Roos, M and Doyle, B and Kuersten, S and Bhatt, AS}, title = {Quantifying bias introduced by sample collection in relative and absolute microbiome measurements.}, journal = {Nature biotechnology}, volume = {42}, number = {2}, pages = {328-338}, pmid = {37106038}, issn = {1546-1696}, support = {Lieberman Fellowship//Stanford University (SU)/ ; T32GM007276//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; P30CA124435//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; 1S10OD02014101//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R01AI14862302//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R01AI14375702//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; }, mesh = {Feces ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; Metagenome ; DNA ; }, abstract = {To gain insight into the accuracy of microbial measurements, it is important to evaluate sources of bias related to sample condition, preservative method and bioinformatic analyses. There is increasing evidence that measurement of the total count and concentration of microbes in the gut, or 'absolute abundance', provides a richer source of information than relative abundance and can correct some conclusions drawn from relative abundance data. However, little is known about how preservative choice can affect these measurements. In this study, we investigated how two common preservatives and short-term storage conditions impact relative and absolute microbial measurements. OMNIgene GUT OMR-200 yields lower metagenomic taxonomic variation between different storage temperatures, whereas Zymo DNA/RNA Shield yields lower metatranscriptomic taxonomic variation. Absolute abundance quantification reveals two different causes of variable Bacteroidetes:Firmicutes ratios across preservatives. Based on these results, we recommend OMNIgene GUT OMR-200 preservative for field studies and Zymo DNA/RNA Shield for metatranscriptomics studies, and we strongly encourage absolute quantification for microbial measurements.}, }
@article {pmid37104445, year = {2023}, author = {Tuniyazi, M and Wang, W and Zhang, N}, title = {A Systematic Review of Current Applications of Fecal Microbiota Transplantation in Horses.}, journal = {Veterinary sciences}, volume = {10}, number = {4}, pages = {}, pmid = {37104445}, issn = {2306-7381}, abstract = {Fecal microbiota transplantation (FMT) is a technique involving transferring fecal matter from a healthy donor to a recipient, with the goal of reinstating a healthy microbiome in the recipient's gut. FMT has been used in horses to manage various gastrointestinal disorders, such as colitis and diarrhea. To evaluate the current literature on the use of FMT in horses, including its efficacy, safety, and potential applications, the authors conducted an extensive search of several databases, including PubMed, MEDLINE, Web of Science, and Google Scholar, published up to 11 January 2023. The authors identified seven studies that met their inclusion criteria, all of which investigated the FMT application as a treatment for gastrointestinal disorders such as colitis and diarrhea. The authors demonstrated that FMT was generally effective in treating these conditions. However, the authors noted that the quality of the studies was generally suboptimal and characterized by small sample sizes and a lack of control groups. The authors concluded that FMT is a promising treatment option for certain gastrointestinal disorders in horses. Nevertheless, more research is required to determine the optimal donor selection, dosing, and administration protocols, as well as the long-term safety and efficacy of FMT in horses.}, }
@article {pmid37104426, year = {2023}, author = {Toresson, L and Spillmann, T and Pilla, R and Ludvigsson, U and Hellgren, J and Olmedal, G and Suchodolski, JS}, title = {Clinical Effects of Faecal Microbiota Transplantation as Adjunctive Therapy in Dogs with Chronic Enteropathies-A Retrospective Case Series of 41 Dogs.}, journal = {Veterinary sciences}, volume = {10}, number = {4}, pages = {}, pmid = {37104426}, issn = {2306-7381}, abstract = {Chronic enteropathies (CE) are common in dogs, but not all affected dogs respond to standard therapy. Successful responses to faecal microbial transplantation (FMT) in dogs with non-responsive CE have been reported in two case series. The objective of this retrospective study was to describe the clinical effects of FMT as an adjunctive therapy in a larger population of dogs with CE. Forty-one dogs aged 0.6-13.0 years (median 5.8) under treatment for CE at one referral animal hospital were included. Dogs were treated with 1-5 (median 3) FMTs as a rectal enema at a dose of 5-7 g/kg body weight. The canine inflammatory bowel disease activity index (CIBDAI) was compared at baseline versus after the last FMT. Stored faecal samples (n = 16) were analysed with the dysbiosis index. CIBDAI at baseline was 2-17 (median 6), which decreased to 1-9 (median 2; p < 0.0001) after FMT. Subsequently, 31/41 dogs responded to treatment, resulting in improved faecal quality and/or activity level in 24/41 and 24/41 dogs, respectively. The dysbiosis index at baseline was significantly lower for good responders versus poor responders (p = 0.043). Results suggest that FMT can be useful as an adjunctive therapy in dogs with poorly responsive CE.}, }
@article {pmid37104044, year = {2023}, author = {Cunningham, A and Harris, DA}, title = {Gut microbiota analysis and faecal transplantation to improve surgical outcomes.}, journal = {The British journal of surgery}, volume = {110}, number = {7}, pages = {757-764}, doi = {10.1093/bjs/znad102}, pmid = {37104044}, issn = {1365-2168}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Feces ; Treatment Outcome ; }, }
@article {pmid37102320, year = {2023}, author = {Tao, J and An, Y and Xu, L and Wang, Y and Wang, C and Li, P and Li, M and Yan, D and Wang, M and Zhong, G and Wu, M}, title = {The protective role of microbiota in the prevention of MPTP/P-induced Parkinson's disease by resveratrol.}, journal = {Food &amp; function}, volume = {14}, number = {10}, pages = {4647-4661}, doi = {10.1039/d2fo03379h}, pmid = {37102320}, issn = {2042-650X}, mesh = {Animals ; Mice ; *Parkinson Disease/drug therapy ; Resveratrol/therapeutic use ; *Neurodegenerative Diseases ; Tyrosine 3-Monooxygenase ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Disease Models, Animal ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; }, abstract = {Parkinson's disease (PD) is a tricky neurodegenerative disease characterized with motor deficits and gastrointestinal (GI) dysfunction. Gut microbiota disturbance is reported to be involved in the clinical phenotypes of PD and its pathogenesis through the brain-gut-microbiota axis. Resveratrol is a natural polyphenol that possesses various biological activities in alleviating many diseases, including PD. The present study was aimed to investigate the role of gut microbiota in resveratrol-treated PD mice. A chronic mouse model of PD was generated via the injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid (MPTP/P) for 5 consecutive weeks. Resveratrol was orally administered once a day (30 mg kg[-1] d[-1]) for a total of 8 weeks. From the 6[th] week to the 8[th] week, fecal microbiota transplantation (FMT) was performed from resveratrol-treated PD mice to PD mice to evaluate the contribution of resveratrol-shaped microbiota in the alleviation of PD. The results showed that FMT from resveratrol-shaped microbiota remarkably alleviated the mice phenotype from PD progression, including increased latency in the rotarod, shortened beam walking time, increased the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta (SNpc) and enriched TH-positive fiber density in the striatum. Further experiments revealed that FMT could ameliorate the GI dysfunction by increasing the small intestinal transport rate and the colon length, decreasing the relative abundances of inflammatory cytokines (TNF-α, IL-6 and IL-1β) in colon epithelial tissue. The 16S rDNA sequencing indicated that FMT attenuated the gut microbial dysbiosis in PD mice by increasing the abundances of Prevotellaceae, Rikenellaceae, Erysipelotrichaceae, Blautia and Alistipes, lowering the ratio of Fimicutes/Bacteroidetes, and decreasing the abundances of Lachnospiraceae and Akkermansia. Therefore, results in this study demonstrated that gut microbiota played a vital role in the prevention of PD progression, and the shaping of the gut microbiota was the pharmacological mechanism of resveratrol in alleviating the phenotype of Parkinson's disease in PD mice.}, }
@article {pmid37101273, year = {2023}, author = {Tie, X and Zhang, Z and Zhou, R and Li, Y and Xu, J and Yin, W}, title = {A case of septic shock due to delayed diagnosis of Cryptosporidium infection after liver transplantation.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {260}, pmid = {37101273}, issn = {1471-2334}, support = {Sichuan Province Science//YiLi/ ; Technology Support Program (No. 2022YFS0379)//YiLi/ ; }, mesh = {Male ; Humans ; *Cryptosporidiosis/diagnosis/drug therapy/complications ; *Shock, Septic/etiology/complications ; *Cryptosporidium/genetics ; *Liver Transplantation/adverse effects ; Hypovolemia/complications/drug therapy ; Antacids/therapeutic use ; Delayed Diagnosis/adverse effects ; Diarrhea/etiology ; }, abstract = {BACKGROUND: Cryptosporidium is recognized as a significant pathogen of diarrhea disease in immunocompromised hosts, and studies have shown that Cryptosporidium infection is high in solid organ transplantation (SOT) patients and often has serious consequences. Because of the lack of specificity of diarrheasymptoms cased by Cryptosporidium infection, it is rarely reported in patients undergoing liver transplantation (LT). It frequently delays diagnosis, coming with severe consequences. In clinical work, diagnosing Cryptosporidium infection in LT patients is also complex but single, and the corresponding anti-infective treatment regimen has not yet been standardized. A rare case of septic shock due to a delayed diagnosis of Cryptosporidium infection after LT and relevant literature are discussed in the passage.<br><br>CASE PRESENTATION: A patient who had received LT for two years was admitted to the hospital with diarrhea more than 20&#xa0;days after eating an unclean diet. After failing treatment at a local hospital, he was admitted to Intensive Care Unit after going into septic shock. The patient presented hypovolemia due to diarrhea, which progressed to septic shock. The patient's sepsis shock was controlled after receiving multiple antibiotic combinations and fluid resuscitation. However, the persistent diarrhea, as the culprit of the patient's electrolyte disturbance, hypovolemia, and malnutrition, was unsolved. The causative agent of diarrhea, Cryptosporidium infection, was identified by colonoscopy, faecal antacid staining, and blood high-throughput sequencing (NGS). The patient was treated by reducing immunosuppression and Nitazoxanide (NTZ), which proved effective in this case.<br><br>CONCLUSION: When LT patients present with diarrhea, clinicians should consider the possibility of Cryptosporidium infection, in addition to screening for conventional pathogens. Tests such as colonoscopy, stool antacid staining and blood NGS sequencing can help diagnose and treat of Cryptosporidium infection early and avoid serious consequences of delayed diagnosis. In treating Cryptosporidium infection in LT patients, the focus should be on the patient's immunosuppressive therapy, striking a balance between anti-immunorejection and anti-infection should be sought. Based on practical experience, NTZ therapy in combination with controlled CD4&#x2009;+&#x2009;T cells at 100-300/mm[3] was highly effective against Cryptosporidium without inducing immunorejection.}, }
@article {pmid37099039, year = {2023}, author = {Sun, J and Xu, G}, title = {Mesenchymal Stem Cell-Derived Exosomal miR-150-3p Affects Intracerebral Hemorrhage By Regulating TRAF6/NF-κB Axis, Gut Microbiota and Metabolism.}, journal = {Stem cell reviews and reports}, volume = {19}, number = {6}, pages = {1907-1921}, pmid = {37099039}, issn = {2629-3277}, mesh = {Animals ; Mice ; Cerebral Hemorrhage/genetics/metabolism ; Disease Models, Animal ; *Gastrointestinal Microbiome/genetics ; *Mesenchymal Stem Cells/metabolism ; *MicroRNAs/genetics/metabolism ; NF-kappa B/genetics/metabolism ; RNA, Ribosomal, 16S/genetics/metabolism ; TNF Receptor-Associated Factor 6/genetics/metabolism ; }, abstract = {Intracerebral hemorrhage (ICH) is a severe subtype of stroke for which there is no effective treatment. Stem cell and exosome (Exo) therapies have great potential as new approaches for neuroprotection and neurorestoration in treating ICH. We aimed to investigate whether Exo affects ICH by regulating the ecology of gut microbiota and metabolism and the mechanisms involved. First, differential miRNAs in ICH were screened by bioinformatics and verified by qRT-PCR. Then, Exo was extracted from mouse bone marrow mesenchymal stem cells (MSCs) and identified. Dual-luciferase reporter gene assay was utilized to verify the binding relationship between miR-150-3p and TRAF6. A mouse ICH model was constructed and treated with Exo. Next, we knocked down miR-150-3p and performed fecal microbiota transplantation (FMT). Then changes in gut microbiota and differential metabolites were detected by 16S rRNA sequencing and metabolomics analysis. We found that miR-150-3p expression was lowest in the brain tissue of the ICH group compared to the Sham group. Besides, low miR-150-3p level in ICH was encapsulated by MSC-derived Exo. Moreover, miR-150-3p bound to TRAF6 and was negatively correlated. With the addition of Exo[miR-150-3p inhibitor], we found that MSC-derived exosomal miR-150-3p may affect ICH injury via TRAF6/NLRP3 axis. MSC-derived exosomal miR-150-3p caused changes in gut microbiota, including Proteobacteria, Muribaculaceae, Lachnospiraceae_NK4A136_group, and Acinetobacter. Moreover, MSC-derived exosomal miR-150-3p caused changes in metabolism. After further FMT, gut microbiota-mediated MSC-derived Exo affected ICH with reduced apoptosis and reduced levels of inflammatory factors. In conclusion, MSC-derived exosomal miR-150-3p affected ICH by regulating TRAF6/NF-κB axis, gut microbiota and metabolism.}, }
@article {pmid37098448, year = {2023}, author = {Porcari, S and Baunwall, SMD and Occhionero, AS and Ingrosso, MR and Ford, AC and Hvas, CL and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: A systematic review and meta-analysis.}, journal = {Journal of autoimmunity}, volume = {141}, number = {}, pages = {103036}, doi = {10.1016/j.jaut.2023.103036}, pmid = {37098448}, issn = {1095-9157}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile ; Treatment Outcome ; Recurrence ; *Inflammatory Bowel Diseases/therapy/etiology ; *Clostridium Infections/therapy/etiology ; }, abstract = {Fecal microbiota transplantation (FMT) is known to be highly effective in patients with recurrent Clostridioides difficile infection (rCDI), but its role in patients who also suffer from inflammatory bowel disease (IBD) is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT for the treatment of rCDI in patients with IBD. We searched the available literature until November 22, 2022 to identify studies that included patients with IBD treated with FMT for rCDI, reporting efficacy outcomes after at least 8 weeks of follow-up. The proportional effect of FMT was summarized with a generalized linear mixed-effect model fitting a logistic regression accounting for different intercepts among studies. We identified 15 eligible studies, containing 777 patients. Overall, FMT achieved high cure rates of rCDI, 81% for single FMT, based on all included studies and patients, and 92% for overall FMT, based on nine studies with 354 patients, respectively. We found a significant advantage of overall FMT over single FMT in improving cure rates of rCDI (from 80% to 92%, p = 0.0015). Serious adverse events were observed in 91 patients (12% of the overall population), with the most common being hospitalisation, IBD-related surgery, or IBD flare. In conclusion, in our meta-analysis FMT achieved high cure rates of rCDI in patients with IBD, with a significant advantage of overall FMT over single FMT, similar to data observed in patients without IBD. Our findings support the use of FMT as a treatment for rCDI in patients with IBD.}, }
@article {pmid37096495, year = {2023}, author = {Minkoff, NZ and Aslam, S and Medina, M and Tanner-Smith, EE and Zackular, JP and Acra, S and Nicholson, MR and Imdad, A}, title = {Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile).}, journal = {The Cochrane database of systematic reviews}, volume = {4}, number = {4}, pages = {CD013871}, pmid = {37096495}, issn = {1469-493X}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Child ; Humans ; Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile ; Clostridioides ; Quality of Life ; Dysbiosis ; Recurrence ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Clostridioides difficile (formerly known as Clostridium difficile) is a bacterium that can cause potentially life-threatening diarrheal illness in individuals with an unhealthy mixture of gut bacteria, known as dysbiosis, and can cause recurrent infections in nearly a third of infected individuals. The traditional treatment of recurrent C difficile infection (rCDI) includes antibiotics, which may further exacerbate dysbiosis. There is growing interest in correcting the underlying dysbiosis in rCDI using of fecal microbiota transplantation (FMT); and there is a need to establish the benefits and harms of FMT for the treatment of rCDI based on data from randomized controlled trials.<br><br>OBJECTIVES: To evaluate the benefits and harms of donor-based fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile infection in immunocompetent people.<br><br>SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 31 March 2022.<br><br>SELECTION CRITERIA: We considered randomized trials of adults or children with rCDI for inclusion. Eligible interventions must have met the definition of FMT, which is the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a person with rCDI. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, no intervention, or antibiotics with activity against C difficile.<br><br>DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. proportion of participants with resolution of rCDI and 2. serious adverse events. Our secondary outcomes were 3. treatment failure, 4. all-cause mortality, 5. withdrawal from study, 6. rate of new CDI infection after a successful FMT, 7. any adverse event, 8. quality of life, and 9. colectomy. We used the GRADE criteria to assess certainty of evidence for each outcome.<br><br>MAIN RESULTS: We included six studies with 320 participants. Two studies were conducted in Denmark, and one each in the Netherlands, Canada, Italy, and the US. Four were single-center and two were multicenter studies. All studies included only adults. Five studies excluded people who were severely immunocompromised, with only one study including 10 participants who were receiving immunosuppressive therapy out of the 64 enrolled; these were similarly distributed between the FMT arm (4/24 or 17%) and comparison arms (6/40 or 15%). The route of administration was the upper gastrointestinal tract via a nasoduodenal tube in one study, two studies used enema only, two used colonoscopic only delivery, and one used either nasojejunal or colonoscopic delivery, depending on a clinical determination of whether the recipient could tolerate a colonoscopy. Five studies had at least one comparison group that received vancomycin. The risk of bias (RoB 2) assessments did not find an overall high risk of bias for any outcome. All six studies assessed the efficacy and safety of FMT for the treatment of rCDI. Pooled results from six studies showed that the use of FMT in immunocompetent participants with rCDI likely leads to a large increase in resolution of rCDI in the FMT group compared to control (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.36 to 2.71; P = 0.02, I[2] = 63%; 6 studies, 320 participants; number needed to treat for an additional beneficial outcome (NNTB) 3; moderate-certainty evidence). Fecal microbiota transplantation probably results in a slight reduction in serious adverse events; however, the CIs around the summary estimate were wide (RR 0.73, 95% CI 0.38 to 1.41; P = 0.24, I&#xb2; = 26%; 6 studies, 320 participants; NNTB 12; moderate-certainty evidence). Fecal microbiota transplantation may result in a reduction in all-cause mortality; however, the number of events was small, and the CIs of the summary estimate were wide (RR 0.57, 95% CI 0.22 to 1.45; P = 0.48, I[2] = 0%; 6 studies, 320 participants; NNTB 20; low-certainty evidence). None of the included studies reported colectomy rates.<br><br>AUTHORS' CONCLUSIONS: In immunocompetent adults with rCDI, FMT likely leads to a large increase in the resolution of recurrent Clostridioides difficile infection compared to alternative treatments such as antibiotics. There was no conclusive evidence regarding the safety of FMT for the treatment of rCDI as the number of events was small for serious adverse events and all-cause mortality. Additional data from large national registry databases might be required to assess any short-term or long-term risks with using FMT for the treatment of rCDI. Elimination of the single study that included some immunocompromised people did not alter these conclusions. Due to the low number of immunocompromised participants enrolled, conclusions cannot be drawn about the risks or benefits of FMT for rCDI in the immunocompromised population.}, }
@article {pmid37095192, year = {2023}, author = {Zhou, X and Zhang, X and Niu, D and Zhang, S and Wang, H and Zhang, X and Nan, F and Jiang, S and Wang, B}, title = {Gut microbiota induces hepatic steatosis by modulating the T cells balance in high fructose diet mice.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {6701}, pmid = {37095192}, issn = {2045-2322}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Fructose/metabolism ; Liver/metabolism ; Diet ; *Non-alcoholic Fatty Liver Disease/metabolism ; Inflammation/metabolism ; Diet, High-Fat ; Mice, Inbred C57BL ; }, abstract = {Metabolic diseases are often associated with high fructose (HF) consumption. HF has also been found to alter the gut microbiota, which then favors the development of nonalcoholic fatty liver disease. However, the mechanisms underlying of the gut microbiota on this metabolic disturbance are yet to be determined. Thus, in this study, we further explored the effect the gut microbiota concerning the T cells balance in an HF diet mouse model. We fed mice 60% fructose-enriched diet for 12 weeks. At 4 weeks, HF diet did not affect the liver, but it caused injury to the intestine and adipose tissues. After 12 weeks, the lipid droplet aggregation was markedly increased in the liver of HF-fed mice. Further analysis of the gut microbial composition showed that HF decreased the Bacteroidetes/Firmicutes ratio and increased the levels of Blautia, Lachnoclostridium, and Oscillibacter. In addition, HF can increase the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the serum. T helper type 1 cells were significantly increased, and regulatory T(Treg) cells were markedly decreased in the mesenteric lymph nodes of the HF-fed mice. Furthermore, fecal microbiota transplantation alleviates systemic metabolic disorder by maintaining liver and intestinal immune homeostasis. Overall, our data indicated that intestinal structure injury and intestinal inflammation might be early, and liver inflammation and hepatic steatosis may be a subsequent effect following HF diets. Gut microbiota disorders impairing the intestinal barrier function and triggering immune homeostasis imbalance may be an importantly responsible for long-term HF diets induced hepatic steatosis.}, }
@article {pmid37094913, year = {2023}, author = {Rinninella, E and Tohumcu, E and Raoul, P and Fiorani, M and Cintoni, M and Mele, MC and Cammarota, G and Gasbarrini, A and Ianiro, G}, title = {The role of diet in shaping human gut microbiota.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {62-63}, number = {}, pages = {101828}, doi = {10.1016/j.bpg.2023.101828}, pmid = {37094913}, issn = {1532-1916}, mesh = {Humans ; *Gastrointestinal Microbiome ; Diet ; *Microbiota ; Intestines ; }, abstract = {Gut microbiota plays a fundamental role within human health, and exerts key functions within the human body. Diet is one of the most powerful modulators of gut microbiota functions and composition. This complex interplay involves also the immune system and the intestinal barrier, highlighting the central role of diet in the pathogenesis and treatment of multiple diseases. In this review article we will paint the landscape of the effects of specific dietary nutrients, and of the detrimental or beneficial outcomes of different dietary patterns, on the composition of human gut microbiota. Moreover, we will discuss the potential application of diet as a therapeutic modulator of gut microbiota, including cutting-edge ways of exploitation, including the use of dietary components as adjuvants to promote microbial engraftment after fecal microbiota transplantation, or personalized nutritional approaches, targeted to the patient microbiome.}, }
@article {pmid37094824, year = {2023}, author = {Imdad, A and Pandit, NG and Zaman, M and Minkoff, NZ and Tanner-Smith, EE and Gomez-Duarte, OG and Acra, S and Nicholson, MR}, title = {Fecal transplantation for treatment of inflammatory bowel disease.}, journal = {The Cochrane database of systematic reviews}, volume = {4}, number = {4}, pages = {CD012774}, pmid = {37094824}, issn = {1469-493X}, mesh = {Adult ; Child ; Humans ; *Colitis, Ulcerative/drug therapy ; *Crohn Disease/drug therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Inflammatory Bowel Diseases ; Quality of Life ; Remission Induction ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract that is thought to be associated with a complex interplay between the immune system, the GI tract lining, the environment, and the gut microbiome, leading to an abnormal inflammatory response in genetically susceptible individuals. An altered composition of the gut's native microbiota, known as dysbiosis, may have a major role in the pathogenesis of ulcerative colitis (UC) and Crohn disease (CD), two subtypes of IBD. There is growing interest in the correction of this underlying dysbiosis using fecal microbiota transplantation (FMT).<br><br>OBJECTIVES: To evaluate the benefits and safety profile of FMT for treatment of IBD in adults and children versus autologous FMT, placebo, standard medication, or no intervention.<br><br>SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two clinical trial registries, and the reference sections of published trials through 22 December 2022.<br><br>SELECTION CRITERIA: We included randomized controlled trials that studied adults and children with UC or CD. Eligible intervention arms used FMT, defined as the delivery of healthy donor stool containing gut microbiota to a recipient's GI tract, to treat UC or CD.<br><br>DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for inclusion. Our primary outcomes were: 1. induction of clinical remission, 2. maintenance of clinical remission, and 3. serious adverse events. Our secondary outcomes were: 4. any adverse events, 5. endoscopic remission, 6. quality of life, 7. clinical response, 8. endoscopic response, 9. withdrawals, 10. inflammatory markers, and 11. microbiome outcomes. We used the GRADE approach to assess the certainty of evidence.<br><br>MAIN RESULTS: We included 12 studies with 550 participants. Three studies were conducted in Australia; two in Canada; and one in each of the following: China, the Czech Republic, France, India, the Netherlands, and the USA. One study was conducted in both Israel and Italy. FMT was administered in the form of capsules or suspensions and delivered by mouth, nasoduodenal tube, enema, or colonoscopy. One study delivered FMT by both oral capsules and colonoscopy. Six studies were at overall low risk of bias, while the others had either unclear or high risk of bias. Ten studies with 468 participants, of which nine studies focused on adults and one focused on children, reported induction of clinical remission in people with UC at longest follow-up (range 6 to 12 weeks) and showed that FMT may increase rates of induction of clinical remission in UC compared to control (risk ratio (RR) 1.79, 95% confidence interval (CI) 1.13 to 2.84; low-certainty evidence). Five studies showed that FMT may increase rates of induction of endoscopic remission in UC at longest follow-up (range 8 to 12 weeks); however, the CIs around the summary estimate were wide and included a possible null effect (RR 1.45, 95% CI 0.64 to 3.29; low-certainty evidence). Nine studies with 417 participants showed that FMT may result in little to no difference in rates of any adverse events (RR 0.99, 95% CI 0.85 to 1.16; low-certainty evidence). The evidence was very uncertain about the risk of serious adverse events (RR 1.77, 95% CI 0.88 to 3.55; very low-certainty evidence) and improvement in quality of life (mean difference (MD) 15.34, 95% CI -3.84 to 34.52; very low-certainty evidence) when FMT was used to induce remission in UC. Two studies, of which one also contributed data for induction of remission in active UC, assessed maintenance of remission in people with controlled UC at longest follow-up (range 48 to 56 weeks). The evidence was very uncertain about the use of FMT for maintenance of clinical remission (RR 2.97, 95% CI 0.26 to 34.42; very low-certainty evidence) and endoscopic remission (RR 3.28, 95% CI 0.73 to 14.74; very low-certainty evidence). The evidence was also very uncertain about the risk of serious adverse events, risk of any adverse events, and improvement in quality of life when FMT was used to maintain remission in UC. None of the included studies assessed use of FMT for induction of remission in people with CD. One study with 21 participants reported data on FMT for maintenance of remission in people with CD. The evidence was very uncertain about the use of FMT for maintenance of clinical remission in CD at 24 weeks (RR 1.21, 95% CI 0.36 to 4.14; very low-certainty evidence). The evidence was also very uncertain about the risk of serious or any adverse events when FMT was used to maintain remission in CD. None of the studies reported data on use of FMT for maintenance of endoscopic remission or improvement in quality of life in people with CD.<br><br>AUTHORS' CONCLUSIONS: FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD.}, }
@article {pmid37094397, year = {2023}, author = {Luo, H and Ying, N and Zhao, Q and Chen, J and Xu, H and Jiang, W and Wu, Y and Wu, Y and Gao, H and Zheng, H}, title = {A novel polysaccharide from Rubus chingii Hu unripe fruits: Extraction optimization, structural characterization and amelioration of colonic inflammation and oxidative stress.}, journal = {Food chemistry}, volume = {421}, number = {}, pages = {136152}, doi = {10.1016/j.foodchem.2023.136152}, pmid = {37094397}, issn = {1873-7072}, mesh = {Mice ; Animals ; *Rubus/chemistry ; Fruit/chemistry ; Polysaccharides/chemistry ; Oxidative Stress ; Inflammation/drug therapy ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; }, abstract = {Raspberry is used as a medicine food homology species and its polysaccharides are worthy being investigated and developed. In the present study, a novel polysaccharide of unripe raspberry fruits (pRCP) was extracted and characterized. The results show that pRCP was an acidic heteropolysaccharide and its Mw value was 74.86 kDa with a high homogeneity. The main chain of pRCP consisted of → 3,6)-β-Galp(1 → and → 5)-α-Araf(1→, and its side chain was composed of α-Araf(1 → linked to the C3 position of → 3,6)-β-Galp(1 →. In addition, pRCP supplementation increased the gut microbial diversity and reduced harmful bacteria including Erysipelatoclostridium and Negativibacillus in high-fat diet (HFD)-fed mice. Treatment with pRCP also alleviated HFD-induced colonic inflammation and oxidative stress in mice. These beneficial effects can be transferred to recipient mice by faecal microbiota transplantation from pRCP-treated mice. Therefore, our study suggests that pRCP could be used as a potential prebiotics to improve intestinal health by modulating the gut microbiota.}, }
@article {pmid37093541, year = {2023}, author = {Anirvan, P and Panigrahi, MK and Singh, SP}, title = {Fecal microbiota transplantation in alcoholic hepatitis: new treatment paradigm or a shot in the dark?.}, journal = {Hepatology international}, volume = {17}, number = {5}, pages = {1318-1319}, pmid = {37093541}, issn = {1936-0541}, mesh = {Humans ; *Hepatitis, Alcoholic/therapy ; Fecal Microbiota Transplantation ; }, }
@article {pmid37093057, year = {2023}, author = {Chen, Q and Fan, Y and Zhang, B and Yan, C and Zhang, Q and Ke, Y and Chen, Z and Wang, L and Shi, H and Hu, Y and Huang, Q and Su, J and Xie, C and Zhang, X and Zhou, L and Ren, J and Xu, H}, title = {Capsulized Fecal Microbiota Transplantation Induces Remission in Patients with Ulcerative Colitis by Gut Microbial Colonization and Metabolite Regulation.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0415222}, pmid = {37093057}, issn = {2165-0497}, mesh = {Humans ; Bacteria ; *Colitis, Ulcerative/therapy/microbiology ; *Communicable Diseases ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) can induce clinical remission in ulcerative colitis (UC) patients. Enemas, nasoduodenal tubes, and colonoscopies are the most common routes for FMT administration. However, there is a lack of definitive evidence regarding the effectiveness of capsulized FMT treatment in UC patients. In this study, we administered capsulized FMT to 22 patients with active UC to assess the efficiency of capsulized FMT and determine the specific bacteria and metabolite factors associated with the response to clinical remission. Our results showed that the use of capsulized FMT was successful in the treatment of UC patients. Capsulized FMT induced clinical remission and clinical response in 57.1% (12 of 21) and 76.2% (16 of 21) of UC patients, respectively. Gut bacterial richness was increased after FMT in patients who achieved remission. Patients in remission after FMT exhibited enrichment of Alistipes sp. and Odoribacter splanchnicus, along with increased levels of indolelactic acid. Patients who did not achieve remission exhibited enrichment of Escherichia coli and Klebsiella and increased levels of biosynthesis of 12,13-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid) and lipopolysaccharides. Furthermore, we identified a relationship between specific bacteria and metabolites and the induction of remission in patients. These findings may provide new insights into FMT in UC treatment and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects. (This study has been registered at ClinicalTrails.gov under registration no. NCT03426683). IMPORTANCE Fecal microbiota transplantation has been successfully used in patients. Recently, capsulized FMT was reported to induce a response in patients with UC. However, limited patients were enrolled in such studies, and the functional factors of capsulized FMT have not been reported in the remission of patients with UC. In this study, we prospectively recruited patients with UC to receive capsulized FMT. First, we found that capsulized FMT could induce clinical remission in 57.1% of patients and clinical response in 76.2% after 12 weeks, which was more acceptable. Second, we found a relationship between the decrease of opportunistic pathogen and lipopolysaccharide synthesis in patients in remission after capsulized FMT. We also identified an association between specific bacteria and metabolites and remission induction in patients after capsulized FMT. These findings put forward a possibility for patients to receive FMT at home and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects.}, }
@article {pmid37091531, year = {2023}, author = {Bachour, SP and Dalal, R and Allegretti, JR}, title = {The impact of the COVID-19 pandemic on Clostridioides difficile infection and utilization of fecal microbiota transplantation.}, journal = {Therapeutic advances in gastroenterology}, volume = {16}, number = {}, pages = {17562848231165581}, pmid = {37091531}, issn = {1756-283X}, abstract = {Previous research has demonstrated that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains cell entry through the angiotensin-converting enzyme 2 receptor, which is abundantly found throughout the gastrointestinal (GI) tract, resulting in a wide array of GI manifestations of coronavirus disease 2019 (COVID-19). By gaining entry into the intestinal epithelial and stromal cells, SARS-CoV-2 has been observed to cause intestinal inflammation and gut dysbiosis. Alterations in gut microbiota are known to be involved in the pathophysiology of Clostridioides difficile infection (CDI). During the initial stages of the COVID-19 pandemic, rates of CDI were similar to historical data despite the increased use of antibiotics. This may be due to increased emphasis on hygiene and protective equipment and reduced C. difficile testing as diarrhea was presumed to be COVID-19 related. Studies also demonstrated additional risk factors for CDI in COVID-19 patients, including length of hospitalization and new abdominal pain during admission. Although not associated with increased mortality, CDI was associated with increased length of hospital stay among patients admitted with COVID-19. Due to fecal viral shedding and concern of oral-fecal transmission of SARS-CoV-2, increased safety regulations were introduced to fecal microbiota transplantation (FMT) leading to reduced rates of this procedure during the COVID-19 pandemic. FMT for recurrent CDI during the COVID-19 pandemic remained highly effective without any reports of SARS-CoV-2 transmission. In addition, limited data show that FMT may be effective in treating COVID-19 and restoring healthy gut microbiota. The goal of this article is to review the impact that the COVID-19 pandemic has had on hospital-acquired CDI and the utilization of FMT.}, }
@article {pmid37089571, year = {2023}, author = {Zhang, M and Sasaki, H and Yang, T and Chen, J and Li, R and Yi, C and Li, J and He, M and Yi, SQ}, title = {Fecal microbiota transplantation from Suncus murinus, an obesity-resistant animal, to C57BL/6NCrSIc mice, and the antibiotic effects in the approach.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1138983}, pmid = {37089571}, issn = {1664-302X}, abstract = {INTRODUCTION: Important studies on the relationship of the intestinal microbial flora with obesity have uncovered profound changes in the composition of the gut microbiota in obese individuals. Animal studies successfully altered body phenotypes by fecal microbiota transplantation (FMT).<br><br>METHODS: In this study, we analyzed the gut microbiome of Suncus murinus (S. murinus), a naturally obesity-resistant animal, and the changes of the gut flora of C57BL/6NCrSIc mice that received gut bacteria transplantation from S. murinus by 16S rRNA gene analysis method. And analyzed and discussed the possible impact of the use of antibiotics before transplantation on the outcome of transplantation.<br><br>RESULTS: Our results showed no significant changes in body weight in the FMT group compared to the control (AB) group, but large fluctuations due to antibiotics. There was no change in blood lipid levels between groups before and after FMT. The gut microbiota of S. murinus were enriched in Firmicutes and Proteobacteria, while Bacteroidetes were not detected, and fewer OTUs were detected in the intestine gut in comparison to other mouse groups. Statistically significant differences in alpha diversity were observed between the FMT group and other groups. Furthermore, a beta diversity analysis indicated an apparent structural separation between the FMT group and other groups.<br><br>CONCLUSION: It was suggested that the gut flora of S. murinus was not well established in the gut trace of mice through FMT, and the administration of antibiotics before transplantation was an important factor affecting the overall composition of the gut flora. Although FMT of S. murinus failed to completely colonize the intestinal tract of the mice, it still had a certain effect on the establishment of the intestinal flora of the mice. The unpredictable effects of pre-transplantation antibiotics on the results of transplantation cannot be ignored.}, }
@article {pmid37089558, year = {2023}, author = {Li, JH and Liu, JL and Li, XW and Liu, Y and Yang, JZ and Chen, LJ and Zhang, KK and Xie, XL and Wang, Q}, title = {Gut microbiota from sigma-1 receptor knockout mice induces depression-like behaviors and modulates the cAMP/CREB/BDNF signaling pathway.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1143648}, pmid = {37089558}, issn = {1664-302X}, abstract = {INTRODUCTION: Depression is a common mental disorder that affects approximately 350 million people worldwide. Much remains unknown about the molecular mechanisms underlying this complex disorder. Sigma-1 receptor (Sig-1R) is expressed at high levels in the central nervous system. Increasing evidence has demonstrated a close association between the Sig-1R and depression. Recently, research has suggested that the gut microbiota may play a crucial role in the development of depression.<br><br>METHODS: Male Sig-1R knockout (Sig-1R KO) and wild-type (WT) mice were used for this study. All transgenic mice were of a pure C57BL/6J background. Mice received a daily gavage of vancomycin (100 mg/kg), neomycin sulfate (200 mg/kg), metronidazole (200 mg/kg), and ampicillin (200 mg/kg) for one week to deplete gut microbiota. Fecal microbiota transplantation (FMT) was conducted to assess the effects of gut microbiota. Depression-like behaviors was evaluated by tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). Gut microbiota was analyzed by 16s rRNA and hippocampal transcriptome changes were assessed by RNA-seq.<br><br>RESULTS: We found that Sig-1R knockout induced depression-like behaviors in mice, including a significant reduction in immobility time and an increase in latency to immobility in the FST and TST, which was reversed upon clearance of gut microbiota with antibiotic treatment. Sig-1R knockout significantly altered the composition of the gut microbiota. At the genus level, the abundance of Alistipes, Alloprevotella, and Lleibacterium decreased significantly. Gut microbiota dysfunction and depression-like phenotypes in Sig-1R knockout mice could be reproduced through FMT experiments. Additionally, hippocampal RNA sequencing identified multiple KEGG pathways that are associated with depression. We also discovered that the cAMP/CREB/BDNF signaling pathway is inhibited in the Sig-1R KO group along with lower expression of neurotrophic factors including CTNF, TGF-&#x3b1; and NGF. Fecal bacteria transplantation from Sig-1R KO mice also inhibited cAMP/CREB/BDNF signaling pathway.<br><br>DISCUSSION: In our study, we found that the gut-brain axis may be a potential mechanism through which Sig-1R regulates depression-like behaviors. Our study provides new insights into the mechanisms by which Sig-1R regulates depression and further supports the concept of the gut-brain axis.}, }
@article {pmid37089545, year = {2023}, author = {Montero, I and Barrientos, D and Hidalgo-Cantabrana, C and Martínez-Álvarez, N}, title = {GutAlive[®] enables DNA-based microbiome analysis without disrupting the original composition and diversity.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1118291}, pmid = {37089545}, issn = {1664-302X}, abstract = {INTRODUCTION: A precise fecal microbiome analysis requires normalized methods for microbiome sampling, transport and manipulation in order to obtain a representative snapshot of the microbial community. GutAlive[®] is the unique stool collection kit that generates an anaerobic atmosphere enabling oxygen sensitive bacteria to survive, maintaining the original microbiome composition and diversity.<br><br>METHODS: Five stool samples from different donors were collected using two different sampling devices, GutAlive[&#xae;] and Zymo DNA/RNA Shield[&#xae;], and processed at four different time points. Shotgun metagenomics was used to evaluate the influence of the device and the processing timing on the microbial populations to unravel the potential fluctuations on the composition and diversity of the fecal microbiome and the metabolic pathways profiling. Additionally, RT-qPCR was used to quantify bacterial cell viability for downstream applications of microbiota samples beyond metagenomics.<br><br>RESULTS: Our results show that GutAlive[&#xae;] enables bacterial cell viability overtime preserving DNA integrity, obtaining high-quantity and high-quality DNA to perform microbiome analysis using shotgun metagenomics. Based on the taxonomic profiling, metabolic pathways analysis, phylogeny and metagenome-assembled genomes, GutAlive[&#xae;] displayed greater performance without significant variability over time, showcasing the stabilization of the microbiome preserving the original composition and diversity. Indeed, this DNA stabilization is enabled with the preservation of bacterial viability on an anaerobic environment inside of the sampling device, without the addition of any reagents that interact directly with sample.<br><br>CONCLUSION: All the above makes GutAlive[&#xae;] an user-friendly kit for self-collection of biological samples, suitable for microbiome analysis, diagnostics, fecal microbiota transplant and bacterial isolation, maintaining the stability and bacterial viability over time, preserving the original composition and diversity of the microbiome.}, }
@article {pmid37087457, year = {2023}, author = {Gu, F and Zhu, S and Hou, J and Tang, Y and Liu, JX and Xu, Q and Sun, HZ}, title = {The hindgut microbiome contributes to host oxidative stress in postpartum dairy cows by affecting glutathione synthesis process.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {87}, pmid = {37087457}, issn = {2049-2618}, mesh = {Animals ; Cattle ; Female ; Mice ; Cysteine ; Glutamates ; *Glutamine ; Glutathione ; *Microbiota ; Oxidative Stress ; Postpartum Period ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Dairy cows are susceptible to postpartum systemic oxidative stress (OS), which leads to significant production loss and metabolic disorders. The gut microbiota has been linked to host health and stress levels. However, to what extent the gut microbiota is associated with postpartum OS remains unknown. In this study, the contribution of the fecal microbiota to postpartum systemic OS and its underlying mechanisms were investigated by integrating 16S rRNA gene sequencing, metagenomics, and metabolomics in postpartum dairy cattle and by transplanting fecal microbiota from cattle to mice.<br><br>RESULTS: A strong link was found between fecal microbial composition and postpartum OS, with an explainability of 43.1%. A total of 17 significantly differential bacterial genera and 19 species were identified between cows with high (HOS) and low OS (LOS). Among them, 9 genera and 16 species showed significant negative correlations with OS, and Marasmitruncus and Ruminococcus_sp._CAG:724 had the strongest correlations. The microbial functional analysis showed that the fecal microbial metabolism of glutamine, glutamate, glycine, and cysteine involved in glutathione synthesis was lower in HOS cows. Moreover, 58 significantly different metabolites were identified between HOS and LOS cows, and of these metabolites, 19 were produced from microbiota or cometabolism of microbiota and host. Furthermore, these microbial metabolites were enriched in the metabolism of glutamine, glutamate, glycine, and cysteine. The mice gavaged with HOS fecal microbiota had significantly higher OS and lower plasma glutathione peroxidase and glutathione content than those orally administered saline or LOS fecal microbiota.<br><br>CONCLUSIONS: Integrated results suggest that the fecal microbiota is responsible for OS and that lower glutathione production plays a causative role in HOS. These findings provide novel insights into the mechanisms of postpartum OS and potential regulatory strategies to alleviate OS in dairy cows. Video Abstract.}, }
@article {pmid37087392, year = {2023}, author = {Mullish, BH and Tohumcu, E and Porcari, S and Fiorani, M and Di Tommaso, N and Gasbarrini, A and Cammarota, G and Ponziani, FR and Ianiro, G}, title = {The role of faecal microbiota transplantation in chronic noncommunicable disorders.}, journal = {Journal of autoimmunity}, volume = {141}, number = {}, pages = {103034}, doi = {10.1016/j.jaut.2023.103034}, pmid = {37087392}, issn = {1095-9157}, mesh = {Humans ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; *Clostridium Infections/therapy ; Treatment Outcome ; Chronic Disease ; }, abstract = {The gut microbiome plays a key role in influencing several pathways and functions involved in human health, including metabolism, protection against infection, and immune regulation. Perturbation of the gut microbiome is recognised as a pathogenic factor in several gastrointestinal and extraintestinal disorders, and is increasingly considered as a therapeutic target in these conditions. Faecal microbiota transplantation (FMT) is the transfer of the microbiota from healthy screened stool donors into the gut of affected patients, and is a well-established and highly effective treatment for recurrent Clostridioides difficile infection. Despite the mechanisms of efficacy of FMT not being fully understood, it has been investigated in several chronic noncommunicable disorders, with variable results. This review aims to give an overview of mechanisms of efficacy of FMT in chronic noncommunicable disorders, and to paint the current landscape of its investigation in these medical conditions, including inflammatory bowel disease (IBD), chronic liver disorders, and also extraintestinal autoimmune conditions.}, }
@article {pmid37087075, year = {2023}, author = {Zhu, M and Ouyang, J and Zhou, F and Zhao, C and Zhu, W and Liu, C and Huang, P and Li, J and Tang, J and Zhang, Z and Huang, J and Wu, M and Wang, K and Liu, Z}, title = {Polysaccharides from Fu brick tea ameliorate obesity by modulating gut microbiota and gut microbiota-related short chain fatty acid and amino acid metabolism.}, journal = {The Journal of nutritional biochemistry}, volume = {118}, number = {}, pages = {109356}, doi = {10.1016/j.jnutbio.2023.109356}, pmid = {37087075}, issn = {1873-4847}, mesh = {Rats ; Animals ; Mice ; *Gastrointestinal Microbiome ; Dysbiosis ; Obesity ; Fatty Acids, Volatile/metabolism ; Tea/chemistry ; Polysaccharides/pharmacology ; Amino Acids/pharmacology ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; }, abstract = {Fu brick tea (FBT) is a traditional tea manufactured by solid-state fermentation of tea leaves (Camellia sinensis). Although anti-obesity effects have been reported for FBT, the associated role of FBT polysaccharides (PSs) and the underlying mechanisms remain unknown. In this study, we found that FBTPSs inhibited obesity, hyperlipidemia, and inflammation; improved intestinal barrier function; and alleviated gut microbiota dysbiosis in high-fat diet-fed rats. Akkermansia muciniphila, Bacteroides, Parasutterella, Desulfovibrio, and Blautia were the core microbes regulated by FBTPSs. FBTPSs regulated the production of gut microbiota-related metabolites, including short-chain fatty acids (SCFAs), branched-chain amino acids, and aromatic amino acids throughout the development of obesity, and regulated the SCFA-GPR signaling pathway. FBTPS-treated fecal microbiota transplant ameliorated obesity, alleviated gut microbiota dysbiosis, and improved gut microbiota-associated metabolites, suggesting that the anti-obesity effect of FBTPSs was gut microbiota-dependent. FBTPSs may serve as novel prebiotic agents for the treatment of obesity and dysbiosis of gut microbiota.}, }
@article {pmid37085966, year = {2023}, author = {Zhong, P and Wu, H and Ma, Y and Xu, X and Jiang, Y and Jin, C and Zhu, Q and Liu, X and Suo, Z and Wang, J}, title = {P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitis.}, journal = {Clinical and translational medicine}, volume = {13}, number = {4}, pages = {e1227}, pmid = {37085966}, issn = {2001-1326}, mesh = {Mice ; Animals ; Receptors, Purinergic P2X4 ; Dysbiosis/chemically induced ; Mice, Inbred C57BL ; *Colitis/chemically induced/genetics ; Inflammation ; *Inflammatory Bowel Diseases/genetics ; *Colitis, Ulcerative/chemically induced/genetics ; Homeostasis ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a non-specific chronic inflammatory disease of the intestine. In addition to genetic susceptibility, environmental factors and dysregulated host immunity, the gut microbiota is implicated in the pathogenesis of Crohn's disease (CD) or ulcerative colitis (UC), the two primary types of IBD. The P2X4 receptor has been demonstrated to have a crucial role in preventing infection, inflammation, and organ damage. However, it remains unclear whether the P2X4 receptor affects IBD and the underlying mechanisms.<br><br>METHODS: Colitis was induced in mice administrated with dextran sodium sulphate (DSS). 16S rDNA sequencing was used to analyze the gut microbiota in knockout and wild-type mice. Clinical and histopathological parameters were monitored throughout the disease progression.<br><br>RESULTS: Gene Expression Omnibus analysis showed the downregulation of P2RX4 (P2rx4) expression in colonic tissues from patients or mice with IBD. However, its expression at the protein levels was upregulated on day 4 or 6 and then downregulated on day 7 in C57BL/6 mice treated with DSS. Gene ablation of P2rx4 aggravated DSS-induced colitis accompanying gut microbiota dysbiosis in mice. Moreover, P2X4 receptor-positive modulator ivermectin alleviated colitis and corrected dysregulated microbiota in wild-type C57BL/6 mice. Further antibiotic-treated gut microbiota depletion, cohousing experiment, and fecal microbiota transplantation proved that gut microbiota dysbiosis was associated with the aggravation of colitis in the mouse model initiated by P2rx4.<br><br>CONCLUSIONS: Our findings elaborate on an unrevealed etiopathophysiological mechanism by which microbiota dysbiosis induced by the P2X4 receptor influences the development of colitis, indicating that the P2X4 receptor represents a promising target for treating patients with CD and UC.}, }
@article {pmid37085337, year = {2023}, author = {Porcari, S and Severino, A and Rondinella, D and Bibbò, S and Quaranta, G and Masucci, L and Maida, M and Scaldaferri, F and Sanguinetti, M and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis.}, journal = {Journal of autoimmunity}, volume = {141}, number = {}, pages = {103033}, doi = {10.1016/j.jaut.2023.103033}, pmid = {37085337}, issn = {1095-9157}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Colitis, Ulcerative/therapy ; *Clostridioides difficile ; Retrospective Studies ; Cohort Studies ; Recurrence ; *Clostridium Infections/complications/drug therapy ; *Inflammatory Bowel Diseases/etiology ; Treatment Outcome ; }, abstract = {AIMS: Clostridioides difficile infection (CDI) is a major challenge for healthcare systems. Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, is a risk factor for primary and recurrent CDI (rCDI). Moreover, CDI itself often worsens the clinical picture of IBD, increasing the risk of complications. Fecal microbiota transplantation (FMT) is a highly effective treatment for rCDI, but data from patients with IBD and CDI are limited and often referred to mixed cohorts. We aimed to report outcomes from a cohort of patients with UC treated with FMT for rCDI superinfection.<br><br>METHODS AND RESULTS: In a retrospective, single-centre cohort study we evaluated characteristics and outcomes of patients with UC who received FMT for rCDI. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Thirty-five patients were included in the analysis. Sixteen patients were cured after single FMT, while 19 patients received repeat FMT. Overall, FMT cured rCDI in 32 patients (91%), and repeat FMT was significantly associated with sustained cure of CDI compared with single FMT (84% vs 50%, p&#xa0;=&#xa0;0.018). Twenty-four patients (69%) experienced remission or an amelioration of UC activity. Serious adverse events were not observed.<br><br>CONCLUSIONS: In our cohort of patients with UC, FMT was highly effective in curing rCDI without severe adverse events and repeat FMT was significantly associated with CDI cure. Most patients also experienced remission or amelioration of UC activity after FMT. Our findings suggest that a sequential FMT protocol may be used routinely in patients with UC and rCDI.}, }
@article {pmid37085058, year = {2023}, author = {Chen, C and Liu, L and Zhong, Y and Wang, M and Ai, Y and Hou, Y and Chen, H and Lin, X and Zhang, Y and Ding, M and Luo, T and Li, J and Li, X and Xiao, X}, title = {Gut microbiota-bile acids-glucagon like peptide-1 axis contributes the resistance to high fat diet-induced obesity in mice.}, journal = {The Journal of nutritional biochemistry}, volume = {117}, number = {}, pages = {109358}, doi = {10.1016/j.jnutbio.2023.109358}, pmid = {37085058}, issn = {1873-4847}, mesh = {Humans ; Animals ; Mice ; *Bile Acids and Salts ; Glucagon-Like Peptide 1/metabolism ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome/physiology ; Mice, Inbred C57BL ; Obesity/metabolism ; }, abstract = {In human and rodents, some individuals may remain lean even when they are challenged with high calorie intake. Here, we used C57BL/6J mice to establish animal models of high-fat diet (HFD) induced obesity sensitive (DIO) mice and obesity resistant (DIR) mice. In DIR mice, improved metabolic profile through brown adipose tissue (BAT) activation was observed, while plasma unconjugated bile acids (BAs) were decreased together with increased intestine tauro-conjugated BAs (e.g., T-β-MCA). The composition of the gut flora also differs greatly between DIR and DOR. Using fecal microbiota transplants from DIR mice, HFD fed recipient mice exhibited a trend toward reduced adiposity and improved glucose tolerance, showing increased serum tauro-conjugated BAs levels. STC-1 cell experiments confirmed T-β-MCA could activate FXR/TGR5 pathway and induce the production of GLP-1, inhibiting genes that regulate the ceramide synthesis. Our results indicated that the DIR mice exhibited higher energy expenditure by activating BAT thermogenesis, which may be related to altered gut microbiota-bile acids-glucagon like peptide-1 axis.}, }
@article {pmid37083877, year = {2023}, author = {Lei, Y and Liu, Q and Li, Q and Zhao, C and Zhao, M and Lu, Q}, title = {Exploring the Complex Relationship Between Microbiota and Systemic Lupus Erythematosus.}, journal = {Current rheumatology reports}, volume = {25}, number = {6}, pages = {107-116}, pmid = {37083877}, issn = {1534-6307}, support = {2022YFC3601800//National Key R&amp;D Program of China/ ; No.2021-I2M-1-059//CAMS Innovation Fund of Medical Sciences/ ; 2020-RC320-003//Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; NO. 81830097//National Natural Science Foundation of China/ ; NO. 32141004//Special Program of National Natural Science Foundation of China/ ; }, mesh = {Humans ; Dysbiosis/microbiology ; Epigenesis, Genetic ; *Lupus Erythematosus, Systemic ; *Microbiota ; *Gastrointestinal Microbiome/physiology ; }, abstract = {PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by various autoantibodies and multi-organ. Microbiota dysbiosis in the gut, skin, oral, and other surfaces has a significant impact on SLE development. This article summarizes relevant research and provides new microbiome-related strategies for exploring the mechanisms and treating patients with SLE.<br><br>RECENT FINDINGS: SLE patients have disruptions in multiple microbiomes, with the gut microbiota (bacteria, viruses, and fungi) and their metabolites being the most thoroughly researched. This dysbiosis can promote SLE progression through mechanisms such as the leaky gut, molecular mimicry, and epigenetic regulation. Notwithstanding study constraints on the relationship between microbiota and SLE, specific interventions targeting the gut microbiota, such as probiotics, dietary management, and fecal microbiota transplantation, have emerged as promising SLE therapeutics.}, }
@article {pmid37083032, year = {2023}, author = {Chancharoenthana, W and Kamolratanakul, S and Schultz, MJ and Leelahavanichkul, A}, title = {The leaky gut and the gut microbiome in sepsis - targets in research and treatment.}, journal = {Clinical science (London, England : 1979)}, volume = {137}, number = {8}, pages = {645-662}, pmid = {37083032}, issn = {1470-8736}, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; *Sepsis ; Inflammation ; Bacteria ; }, abstract = {Both a leaky gut (a barrier defect of the intestinal surface) and gut dysbiosis (a change in the intestinal microbial population) are intrinsic to sepsis. While sepsis itself can cause dysbiosis, dysbiosis can worsen sepsis. The leaky gut syndrome refers to a status with which there is an increased intestinal permeability allowing the translocation of microbial molecules from the gut into the blood circulation. It is not just a symptom of gastrointestinal involvement, but also an underlying cause that develops independently, and its presence could be recognized by the detection, in blood, of lipopolysaccharides and (1→3)-β-D-glucan (major components of gut microbiota). Gut-dysbiosis is the consequence of a reduction in some bacterial species in the gut microbiome, as a consequence of intestinal mucosal immunity defect, caused by intestinal hypoperfusion, immune cell apoptosis, and a variety of enteric neuro-humoral-immunity responses. A reduction in bacteria that produce short-chain fatty acids could change the intestinal barriers, leading to the translocation of pathogen molecules, into the circulation where it causes systemic inflammation. Even gut fungi might be increased in human patients with sepsis, even though this has not been consistently observed in murine models of sepsis, probably because of the longer duration of sepsis and also antibiotic use in patients. The gut virobiome that partly consists of bacteriophages is also detectable in gut contents that might be different between sepsis and normal hosts. These alterations of gut dysbiosis altogether could be an interesting target for sepsis adjuvant therapies, e.g., by faecal transplantation or probiotic therapy. Here, current information on leaky gut and gut dysbiosis along with the potential biomarkers, new treatment strategies, and future research topics are mentioned.}, }
@article {pmid37081964, year = {2023}, author = {Bao, K and Wang, M and Liu, L and Zhang, D and Jin, C and Zhang, J and Shi, L}, title = {Jinhong decoction protects sepsis-associated acute lung injury by reducing intestinal bacterial translocation and improving gut microbial homeostasis.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1079482}, pmid = {37081964}, issn = {1663-9812}, abstract = {Background: Currently no specific treatments are available for sepsis and the associated syndromes including acute lung injury (ALI). Jinhong Decoction (JHD) is a traditional Chinese prescription, and it has been applied clinically as an efficient and safe treatment for sepsis, but the underlying mechanism remains unknown. The aim of the study was to explore the potential mechanisms of JHD ameliorating sepsis and concurrent ALI. Methods: The cecum ligation puncture (CLP)- induced murine sepsis model was established for determining the efficacy of JHD protecting CLP and ALI. The role of gut microbiota involved in the efficacy of JHD was evaluated by 16S rRNA sequencing and fecal microbiota transplantation (FMT). Translocation of intestinal Escherichia coli (E. coli) to lungs after CLP was verified by qPCR and in vivo-imaging. Intestinal permeability was analyzed by detecting FITC-dextran leakness. Junction proteins were evaluated by Western blotting and immunofluorescence. Results: JHD treatment remarkably increased survival rate of septic mice and alleviated sepsis-associated lung inflammation and injury. FMT suggested that the protective role for JHD was mediated through the regulation of gut microbiota. We further revealed that JHD administration partially restored the diversity and configuration of microbiome that was distorted by CLP operation. Of interest, the intestinal bacteria, E. coli particularly, was found to translocate into the lungs upon CLP via disrupting the intestinal mucosal barrier, leading to the inflammatory response and tissue damage in lungs. JHD impeded the migration and hence lung accumulation of intestinal E. coli, and thereby prevented severe ALI associated with sepsis. This effect is causatively related with the ability of JHD to restore intestinal barrier by up-regulating tight junctions. Conclusion: Our study unveils a mechanism whereby the migration of gut bacteria leads to sepsis-associated ALI, and we demonstrate the potential of JHD as an effective strategy to block this bacterial migration for treating sepsis and the associated immunopathology in the distal organs.}, }
@article {pmid37078497, year = {2023}, author = {Zhou, B and Pang, X and Wu, J and Liu, T and Wang, B and Cao, H}, title = {Gut microbiota in COVID-19: new insights from inside.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2201157}, pmid = {37078497}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {The epidemic of coronavirus disease-19 (COVID-19) has grown to be a global health threat. Gastrointestinal symptoms are thought to be common clinical manifestations apart from a series of originally found respiratory symptoms. The human gut harbors trillions of microorganisms that are indispensable for complex physiological processes and homeostasis. Growing evidence demonstrate that gut microbiota alteration is associated with COVID-19 progress and severity, and post-COVID-19 syndrome, characterized by decrease of anti-inflammatory bacteria like Bifidobacterium and Faecalibacterium and enrichment of inflammation-associated microbiota including Streptococcus and Actinomyces. Therapeutic strategies such as diet, probiotics/prebiotics, herb, and fecal microbiota transplantation have shown positive effects on relieving clinical symptoms. In this article, we provide and summarize the recent evidence about the gut microbiota and their metabolites alterations during and after COVID-19 infection and focus on potential therapeutic strategies targeting gut microbiota. Understanding the connections between intestinal microbiota and COVID-19 would provide new insights into COVID-19 management in the future.}, }
@article {pmid37077050, year = {2023}, author = {Wu, LQ and Yuan, QF and Qin, ZC and Xu, YD and Li, L and Xu, JT and He, XX and Xie, WR and Wu, LH}, title = {Faecal microbiota transplantation for treatment of chronic urticaria with recurrent abdominal pain and food allergy.}, journal = {Singapore medical journal}, volume = {}, number = {}, pages = {}, doi = {10.4103/singaporemedj.SMJ-2021-423}, pmid = {37077050}, issn = {2737-5935}, }
@article {pmid37076953, year = {2023}, author = {Li, J and Zhang, F and Zhao, L and Dong, C}, title = {Microbiota-gut-brain axis and related therapeutics in Alzheimer's disease: prospects for multitherapy and inflammation control.}, journal = {Reviews in the neurosciences}, volume = {34}, number = {6}, pages = {695-718}, pmid = {37076953}, issn = {2191-0200}, mesh = {Humans ; Aged ; *Alzheimer Disease/drug therapy/pathology ; Brain-Gut Axis ; Brain ; Inflammation/drug therapy ; }, abstract = {Alzheimer's disease (AD) is the most common type of dementia in the elderly and causes neurodegeneration, leading to memory loss, behavioral disorder, and psychiatric impairment. One potential mechanism contributing to the pathogenesis of AD may be the imbalance in gut microbiota, local and systemic inflammation, and dysregulation of the microbiota-gut-brain axis (MGBA). Most of the AD drugs approved for clinical use today are symptomatic treatments that do not improve AD pathologic changes. As a result, researchers are exploring novel therapeutic modalities. Treatments involving the MGBA include antibiotics, probiotics, transplantation of fecal microbiota, botanical products, and others. However, single-treatment modalities are not as effective as expected, and a combination therapy is gaining momentum. The purpose of this review is to summarize recent advances in MGBA-related pathological mechanisms and treatment modalities in AD and to propose a new concept of combination therapy. "MGBA-based multitherapy" is an emerging view of treatment in which classic symptomatic treatments and MGBA-based therapeutic modalities are used in combination. Donepezil and memantine are two commonly used drugs in AD treatment. On the basis of the single/combined use of these two drugs, two/more additional drugs and treatment modalities that target the MGBA are chosen based on the characteristics of the patient's condition as an adjuvant treatment, as well as the maintenance of good lifestyle habits. "MGBA-based multitherapy" offers new insights for the treatment of cognitive impairment in AD patients and is expected to show good therapeutic results.}, }
@article {pmid37075927, year = {2023}, author = {Rakotonirina, A and Galperine, T and Audry, M and Kroemer, M and Baliff, A and Carrez, L and Sadeghipour, F and Schrenzel, J and Guery, B and Allémann, E}, title = {Dry alginate beads for fecal microbiota transplantation: From model strains to fecal samples.}, journal = {International journal of pharmaceutics}, volume = {639}, number = {}, pages = {122961}, doi = {10.1016/j.ijpharm.2023.122961}, pmid = {37075927}, issn = {1873-3476}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridioides difficile ; Treatment Outcome ; Feces/microbiology ; *Clostridium Infections/therapy/microbiology ; }, abstract = {Clostridioides difficile infection (CDI) is a critical nosocomial infection with more than 124,000 cases per year in Europe and a mortality rate of 15-17 %. The standard of care (SoC) is antibiotic treatment. Unfortunately, the relapse rate is high (∼35 %) and SoC is significantly less effective against recurrent infection (rCDI). Fecal microbiota transplantation (FMT) is a recommended treatment against rCDI from the second recurrence episode and has an efficacy of 90 %. The formulation of diluted donor stool deserves innovation because its actual administration routes deserve optimization (naso-duodenal/jejunal tubes, colonoscopy, enema or several voluminous oral capsules). Encapsulation of model bacteria strains in gel beads were first investigated. Then, the encapsulation method was applied to diluted stools. Robust spherical gel beads were obtained. The mean particle size was around 2 mm. A high loading of viable microorganisms was obtained for model strains and fecal samples. For plate-counting, values ranged from 10[15] to 10[17] CFU/g for single and mixed model strains, and 10[6] to 10[8] CFU/g for fecal samples. This corresponded to a viability of 30 % to 60 % as assessed by flow cytometry. This novel formulation is promising as the technology is applicable to both model strains and bacteria contained in the gut microbiota.}, }
@article {pmid37074200, year = {2023}, author = {Chen, Q and Ma, X and Xing, Z and Zhao, X and Zu, H and Guo, Z and Li, B}, title = {Antibiotic Conditioning Shapes Pseudosterile Mouse Models by Deleting Colonic Microbes Rather than Small Intestinal Microbes.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0081423}, pmid = {37074200}, issn = {2165-0497}, mesh = {Animals ; Mice ; *Anti-Bacterial Agents/pharmacology ; RNA, Ribosomal, 16S/genetics ; *Gastrointestinal Microbiome ; Intestine, Small ; Colon ; }, abstract = {A simple model of alternative microbiota in the developing intestinal environment has been highly desirable for the study of health and disease in the gut. The pattern of antibiotic depletion of natural gut microbes is necessary for this model. However, the effects and loci of antibiotic deletion of gut microbes remain unclear. In this study, a mixture of three proven broad-spectrum antibiotics was selected to study their effects on microbial deletions in the jejunum, ileum, and colon of mice. The 16S rRNA sequencing results showed that antibiotics significantly reduced colonic microbial diversity, with limited effects on the jejunum and ileum. At the level of microbial genera, only 93.38% of Burkholderia-Caballeronia-Paraburkholderia and 5.89% of Enterorhabdus were present in the colon after antibiotic treatment. However, such changes were not observed in the microbial composition of the jejunum and ileum. Our results suggest that the antibiotics depleted intestinal microorganisms by acting primarily in the colon and not in the small intestine (jejunum and ileum). IMPORTANCE Many studies have applied antibiotics to delete intestinal microbes to shape pseudosterile mouse models and further used for fecal microbial transplantation. However, few studies have explored the spatial location of antibiotic action in the intestine. This study shows that the selected antibiotics effectively deleted microbiota in the colon of mice, with limited effects on microbes in the jejunum and ileum. Our study provides guidance for the application of a mouse model of antibiotic deletion of intestinal microbes.}, }
@article {pmid37069691, year = {2023}, author = {Zhao, C and Hu, X and Qiu, M and Bao, L and Wu, K and Meng, X and Zhao, Y and Feng, L and Duan, S and He, Y and Zhang, N and Fu, Y}, title = {Sialic acid exacerbates gut dysbiosis-associated mastitis through the microbiota-gut-mammary axis by fueling gut microbiota disruption.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {78}, pmid = {37069691}, issn = {2049-2618}, mesh = {Humans ; Female ; Animals ; Cattle ; Mice ; *Gastrointestinal Microbiome/physiology ; N-Acetylneuraminic Acid ; Dysbiosis/chemically induced ; *Mastitis ; *Microbiota ; Enterobacteriaceae ; Escherichia coli ; }, abstract = {BACKGROUND: Mastitis is one of the most severe diseases in humans and animals, especially on dairy farms. Mounting evidence indicates that gastrointestinal dysbiosis caused by induction of subacute ruminal acidosis (SARA) by high-grain diet consumption and low in dietary fiber is associated with mastitis initiation and development, however, the underlying mechanism remains unknown.<br><br>RESULTS: In the present study, we found that cows with SARA-associated mastitis have altered metabolic profiles in the rumen, with increased sialic acids level in particular. Consumption of sialic acid (SA) in antibiotic-treated mice, but not healthy mice, induced marked mastitis. SA treatment of antibiotic-treated mice also induced mucosal and systemic inflammatory responses, as evidenced by increased colon and liver injuries and several inflammatory markers. In addition, gut dysbiosis caused by antibiotic impaired gut barrier integrity, which was aggravated by SA treatment. SA potentiated serum LPS level caused by antibiotic treatment, leading to increased activation of the TLR4-NF-&#x3ba;B/NLRP3 pathways in the mammary gland and colon. Moreover, SA facilitated gut dysbiosis caused by antibiotic, and especially enhanced Enterobacteriaceae and Akkermansiaceae, which correlated with mastitis parameters. Fecal microbiota transplantation from SA-antibiotic-treated mice mimicked mastitis in recipient mice. In vitro experiments showed that SA prompted Escherichia coli growth and virulence gene expression, leading to higher proinflammatory cytokine production in macrophages. Targeting the inhibition of Enterobacteriaceae by sodium tungstate or treating with the commensal Lactobacillus reuteri alleviated SA-facilitated mastitis. In addition, SARA cows had distinct ruminal microbial structure by the enrichment of SA-utilizing opportunistic pathogenic Moraxellaceae and the depletion of SA-utilizing commensal Prevotellaceae. Treating mice with the specific sialidase inhibitor zanamivir reduced SA production and Moraxellaceae abundance, and improved mastitis in mice caused by ruminal microbiota transplantation from cows with SARA-associated mastitis.<br><br>CONCLUSIONS: This study, for the first time, indicates that SA aggravates gut dysbiosis-induced mastitis by promoting gut microbiota disturbance and is regulated by commensal bacteria, indicating the important role of the microbiota-gut-mammary axis in mastitis pathogenesis and suggesting a potential strategy for mastitis intervention based on gut metabolism regulation. Video Abstract.}, }
@article {pmid37069665, year = {2023}, author = {Watson, AR and Füssel, J and Veseli, I and DeLongchamp, JZ and Silva, M and Trigodet, F and Lolans, K and Shaiber, A and Fogarty, E and Runde, JM and Quince, C and Yu, MK and Söylev, A and Morrison, HG and Lee, STM and Kao, D and Rubin, DT and Jabri, B and Louie, T and Eren, AM}, title = {Metabolic independence drives gut microbial colonization and resilience in health and disease.}, journal = {Genome biology}, volume = {24}, number = {1}, pages = {78}, pmid = {37069665}, issn = {1474-760X}, support = {P30 CA014599/CA/NCI NIH HHS/United States ; P30 DK042086/DK/NIDDK NIH HHS/United States ; RC2 DK122394/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Microbiota ; Metagenomics ; Amino Acids ; Feces ; }, abstract = {BACKGROUND: Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge.<br><br>RESULTS: Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients.<br><br>CONCLUSIONS: These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of "dysbiosis" that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.}, }
@article {pmid37069399, year = {2023}, author = {Fan, Y and Støving, RK and Berreira Ibraim, S and Hyötyläinen, T and Thirion, F and Arora, T and Lyu, L and Stankevic, E and Hansen, TH and Déchelotte, P and Sinioja, T and Ragnarsdottir, O and Pons, N and Galleron, N and Quinquis, B and Levenez, F and Roume, H and Falony, G and Vieira-Silva, S and Raes, J and Clausen, L and Telléus, GK and Bäckhed, F and Oresic, M and Ehrlich, SD and Pedersen, O}, title = {The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice.}, journal = {Nature microbiology}, volume = {8}, number = {5}, pages = {787-802}, pmid = {37069399}, issn = {2058-5276}, mesh = {Humans ; Female ; Animals ; Mice ; Male ; *Gastrointestinal Microbiome ; *Anorexia Nervosa/microbiology ; Metabolomics ; Feces/microbiology ; Feeding Behavior ; Bacteria/genetics ; }, abstract = {Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis.}, }
@article {pmid37067507, year = {2023}, author = {Wang, HR and Wang, MY and Sang, LX}, title = {How to Choose a Treatment for Immune Checkpoint Inhibitor-associated Colitis: Biologics, or Fecal Microbial Transplantation.}, journal = {Inflammatory bowel diseases}, volume = {29}, number = {8}, pages = {e33-e34}, doi = {10.1093/ibd/izad071}, pmid = {37067507}, issn = {1536-4844}, mesh = {Humans ; Immune Checkpoint Inhibitors ; *Biological Products/adverse effects ; *Colitis/therapy/drug therapy ; *Antineoplastic Agents, Immunological/adverse effects ; Fecal Microbiota Transplantation ; }, }
@article {pmid37067423, year = {2023}, author = {Wang, D and Zheng, Y and Fan, Y and He, Y and Liu, K and Deng, S and Liu, Y}, title = {Sodium Humate-Derived Gut Microbiota Ameliorates Intestinal Dysfunction Induced by Salmonella Typhimurium in Mice.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0534822}, pmid = {37067423}, issn = {2165-0497}, mesh = {Humans ; Animals ; Mice ; Salmonella typhimurium ; *Gastrointestinal Microbiome ; *Salmonella Infections, Animal/microbiology ; Intestines ; *Enteritis ; }, abstract = {Salmonella is a foodborne pathogen that is one of the main causes of gastroenteric disease in humans and animals. As a natural organic substance, sodium humate (HNa) possesses antibacterial, antidiarrheal, and anti-inflammatory properties. However, it is unclear whether the HNa and HNa-derived microbiota exert alleviative effects on Salmonella enterica serovar Typhimurium-induced enteritis. We found that treatment with HNa disrupted the cell wall of S. Typhimurium and decreased the virulence gene expression. Next, we explored the effect of HNa presupplementation on S. Typhimurium-induced murine enteritis. The results revealed that HNa ameliorated intestinal pathological damage. In addition, we observed that presupplementation with HNa enhanced intestinal barrier function via modulating gut microbiota, downregulating toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) and NOD-like receptor protein 3 (NLRP3) signaling pathways, regulating intestinal mucosal immunity, and enhancing tight junction protein expression. To further validate the effect of HNa-derived microbiota on S. Typhimurium-induced enteritis, we performed fecal microbiota transplantation and found that HNa-derived microbiota also alleviated S. Typhimurium-induced intestinal damage. It is noteworthy that both HNa and HNa-derived microbiota improved the liver injury caused by S. Typhimurium infection. Collectively, this is the first study to confirm that HNa could alleviate S. Typhimurium-induced enteritis in a gut microbiota-dependent manner. This study provides a new perspective on HNa as a potential drug to prevent and treat salmonellosis. IMPORTANCE Salmonella Typhimurium is an important zoonotic pathogen, widely distributed in nature. S. Typhimurium is one of the leading causes of foodborne illnesses worldwide, and more than 350,000 people died from Salmonella infection each year, which poses a substantial risk to public health and causes a considerable economic loss. Here, we found that the S. Typhimurium infection caused severe intestinal and liver damage. In addition, we first found that sodium humate (HNa) and HNa-derived gut microbiota can alleviate S. Typhimurium infection-induced intestinal damage. These findings extend the knowledge about the public health risk and pathogenic mechanisms of S. Typhimurium.}, }
@article {pmid37062804, year = {2023}, author = {Baek, OD and Hjermitslev, CK and Dyreborg, L and Baunwall, SMD and Høyer, KL and Rågård, N and Hammeken, LH and Povlsen, JV and Ehlers, LH and Hvas, CL}, title = {Early Economic Assessment of Faecal Microbiota Transplantation for Patients with Urinary Tract Infections Caused by Multidrug-Resistant Organisms.}, journal = {Infectious diseases and therapy}, volume = {12}, number = {5}, pages = {1429-1436}, pmid = {37062804}, issn = {2193-8229}, support = {8056-00006B//Innovationsfonden/ ; NNF22OC0074080//Novo Nordisk Fonden/ ; }, abstract = {INTRODUCTION: The use of faecal microbiota transplantation (FMT) to eradicate intestinal carriage of multidrug-resistant organisms (MDRO) has been described in case reports and small case series. Although few in numbers, these patients suffer from recurrent infections that may exacerbate both the patients' comorbidities and their healths. In the current study, we hypothesized that FMT for MDRO-related urinary tract infections (UTIs) reduces hospitalisations and associated costs.<br><br>METHODS: In a cohort of patients referred for FMT from 2015 to 2020, we selected all patients who had consecutively been referred for eradication of MRDO carriage with UTIs. An early economic assessment was performed to calculate hospital-related costs. The overall study cohort was registered at ClinicalTrials, study identifier NCT03712722.<br><br>RESULTS: We consecutively included five patients with UTIs caused by MDROs. Four of the patients were renal transplant recipients. Patients were followed for median 126&#xa0;days (range 60-320), where the follow-up duration for each patient was aligned with the number of days from the first UTI to FMT. The median number of UTIs per patient dropped from 4 to 0. Investigating hospital costs, hospital admission days dropped by 87% and monthly hospital costs by 79%.<br><br>CONCLUSIONS: FMT was effective in reducing the occurrence of UTIs and mediated a marked reduction in hospital costs. We suggest that this strategy is cost-effective.<br><br>TRIAL REGISTRATION: ClinicalTrials, study identifier NCT03712722.}, }
@article {pmid37062174, year = {2023}, author = {Benech, N and Sokol, H}, title = {Targeting the gut microbiota in inflammatory bowel diseases: where are we?.}, journal = {Current opinion in microbiology}, volume = {74}, number = {}, pages = {102319}, doi = {10.1016/j.mib.2023.102319}, pmid = {37062174}, issn = {1879-0364}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Microbiota ; Fecal Microbiota Transplantation ; Bacteria/genetics ; Inflammation ; }, abstract = {The gut microbiota is now recognized to be a key driver of mucosal inflammation in inflammatory bowel disease (IBD). Robust functional and compositional alterations of the gut microbiota have been described in IBD with a reduction in bacterial diversity, a reduction in some anti-inflammatory anaerobic bacteria, and an increase in bacteria with pro-inflammatory potential. However, despite 15 years of active research, therapeutical applications are still lacking. Recent studies have shed new light on how targeting the gut microbiota can be beneficial in IBD with fecal microbiota transplantation, next-generation probiotics, and phage therapy. Given the similarities in dysfunction and structure of the gut microbiota between IBD and other chronic conditions associated with intestinal inflammation, such as celiac disease, Familial Mediterranean Fever, or common variable immunodeficiency, common therapeutic strategies targeting the host-microbiota symbiosis may be applied in these different conditions.}, }
@article {pmid37059245, year = {2023}, author = {Gu, YY and Cui, XB and Jiang, J and Zhang, YX and Liu, MH and Cheng, SB and Li, YY and Liu, LL and Liao, RX and Zhao, P and Jin, W and Jia, YH and Wang, J and Zhou, FH}, title = {Dingxin recipe Ⅲ ameliorates hyperlipidemia injury in SD rats by improving the gut barrier, particularly the SCFAs/GPR43 pathway.}, journal = {Journal of ethnopharmacology}, volume = {312}, number = {}, pages = {116483}, doi = {10.1016/j.jep.2023.116483}, pmid = {37059245}, issn = {1872-7573}, mesh = {Rats ; Animals ; *Hyperlipidemias/drug therapy ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Lipids ; Fatty Acids, Volatile/metabolism ; }, abstract = {Dingxin Recipe Ⅲ (DXR Ⅲ) is a traditional Chinese medicine compound used for hyperlipidemia treatment in clinical practice. However, its curative effects and pharmacological mechanisms in hyperlipidemia have not been clarified to date.<br><br>AIM OF THE STUDY: Studies have demonstrated that gut barrier was strongly implicated in lipid deposition. Based on gut barrier and lipid metabolism, this study examined the effects and molecular mechanisms of DXR &#x2162; in hyperlipidemia.<br><br>MATERIALS AND METHODS: The bioactive compounds of DXR &#x2162; were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and its effects were evaluated in high-fat diet-fed rats. Specifically, the serum levels of lipids and hepatic enzymes were measured using the appropriate kits; colon and liver sections were obtained for histological analyses; gut microbiota and metabolites were analyzed by 16S rDNA sequencing and liquid chromatography-MS/MS; and the expression of genes and proteins was determined by real-time quantitative polymerase chain reaction and western blotting and immunohistochemistry, respectively. The pharmacological mechanisms of DXR &#x2162; were further explored by fecal microbiota transplantation and short-chain fatty acid (SCFAs)-based interventions.<br><br>RESULTS: DXR &#x2162; treatment significantly downregulated serum lipid levels, mitigated hepatocyte steatosis and improved lipid metabolism. Moreover, DXR &#x2162; improved the gut barrier, specifically by improving the physical barrier in the colon, causing part composition changes in the gut microbiota, and increasing the serum SCFAs level. DXR &#x2162; also upregulated the expression of colon GPR43/GPR109A. Fecal microbiota transplantation from rats treated with DXR &#x2162; downregulated part hyperlipidemia-related phenotypes, while the SCFAs intervention significantly improved most of the hyperlipidemia-related phenotypes and upregulated the expression of GPR43. Moreover, both DXR &#x2162; and SCFAs upregulated the expression of colon ABCA1.<br><br>CONCLUSION: DXR &#x2162; protects against hyperlipidemia by improving the gut barrier, particularly the SCFAs/GPR43 pathway.}, }
@article {pmid37055440, year = {2023}, author = {Song, W and Sheng, Q and Bai, Y and Li, L and Ning, X and Liu, Y and Song, C and Wang, T and Dong, X and Luo, Y and Hu, J and Zhu, L and Cui, X and Chen, B and Li, L and Cai, C and Cui, H and Yue, T}, title = {Obesity, but not high-fat diet, is associated with bone loss that is reversed via CD4[+]CD25[+]Foxp3[+] Tregs-mediated gut microbiome of non-obese mice.}, journal = {NPJ science of food}, volume = {7}, number = {1}, pages = {14}, pmid = {37055440}, issn = {2396-8370}, support = {31901701//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Osteoporosis is characterized by decreased bone mass, microarchitectural deterioration, and increased bone fragility. High-fat diet (HFD)-induced obesity also results in bone loss, which is associated with an imbalanced gut microbiome. However, whether HFD-induced obesity or HFD itself promotes osteoclastogenesis and consequent bone loss remains unclear. In this study, we developed HFD-induced obesity (HIO) and non-obesity (NO) mouse models to evaluate the effect of HFD on bone loss. NO mice were defined as body weight within 5% of higher or lower than that of chow diet fed mice after 10 weeks HFD feeding. NO was protected from HIO-induced bone loss by the RANKL /OPG system, with associated increases in the tibia tenacity, cortical bone mean density, bone volume of cancellous bone, and trabecular number. This led to increased bone strength and improved bone microstructure via the microbiome-short-chain fatty acids (SCFAs) regulation. Additionally, endogenous gut-SCFAs produced by the NO mice activated free fatty acid receptor 2 and inhibited histone deacetylases, resulting in the promotion of Treg cell proliferation in the HFD-fed NO mice; thereby, inhibiting osteoclastogenesis, which can be transplanted by fecal microbiome. Furthermore, T cells from NO mice retain differentiation of osteoclast precursors of RAW 264.7 macrophages ex vivo. Our data reveal that HFD is not a deleterious diet; however, the induction of obesity serves as a key trigger of bone loss that can be blocked by a NO mouse-specific gut microbiome.}, }
@article {pmid37052201, year = {2023}, author = {Jansen, D and Falony, G and Vieira-Silva, S and Simsek, C and Marcelis, T and Caenepeel, C and Machiels, K and Raes, J and Vermeire, S and Matthijnssens, J}, title = {Community Types of the Human Gut Virome are Associated with Endoscopic Outcome in Ulcerative Colitis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {17}, number = {9}, pages = {1504-1513}, pmid = {37052201}, issn = {1876-4479}, support = {1S78021N//Fonds Wetenschappelijk Onderzoek/ ; }, mesh = {Humans ; *Virome ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/virology/therapy ; Male ; Female ; *Feces/virology/microbiology ; Adult ; Middle Aged ; Bacteriophages/isolation &amp; purification ; Dysbiosis/virology ; Treatment Outcome ; High-Throughput Nucleotide Sequencing ; }, abstract = {BACKGROUND: Inflammatory bowel disease [IBD] is a major debilitating disease. Recently, the gut microbiota has gained attention as an important factor involved in the pathophysiology of IBD. As a complement to the established bacterial 'enterotypes' associated with IBD, we focused here on viruses. We investigated the intestinal virome of IBD patients undergoing biological therapy for the presence of virome configurations associated with IBD, and to uncover how those configurations are associated with therapeutic success.<br><br>METHODS: Viral-like particle enrichment followed by deep sequencing was performed on 432 faecal samples from 181 IBD patients starting biological therapy. Redundancy analysis and Dirichlet Multinomial Mixtures were applied to determine covariates of the virome composition and to condense the gut virota into 'viral community types', respectively.<br><br>RESULTS: Patients were stratified based on unsupervised clustering into two viral community types. Community type CA showed a low &#x3b1;-diversity and a high relative abundance of Caudoviricetes [non-CrAss] phages and was associated with the dysbiotic Bact2-enterotype. Community type CrM showed a high &#x3b1;-diversity and a high relative abundance of Crassvirales and Malgrandaviricetes phages. During post-interventional analysis, endoscopic outcome was associated with gut virome composition. Remitting UC patients had a high percentage of community type CrM, a high Shannon diversity and a low lysogenic potential. Pre-interventional analyses also identified five novel phages associated with treatment success.<br><br>CONCLUSIONS: This study proposed two gut virome configurations that may be involved in the pathophysiology of IBD. Interestingly, those viral configurations are further associated with therapeutic success, suggesting a potential clinical relevance.}, }
@article {pmid37049583, year = {2023}, author = {Hoelz, H and Heetmeyer, J and Tsakmaklis, A and Hiergeist, A and Siebert, K and De Zen, F and Häcker, D and Metwaly, A and Neuhaus, K and Gessner, A and Vehreschild, MJGT and Haller, D and Schwerd, T}, title = {Is Autologous Fecal Microbiota Transfer after Exclusive Enteral Nutrition in Pediatric Crohn's Disease Patients Rational and Feasible? Data from a Feasibility Test.}, journal = {Nutrients}, volume = {15}, number = {7}, pages = {}, pmid = {37049583}, issn = {2072-6643}, support = {395357507//Deutsche Forschungsgemeinschaft/ ; 2847//Leona M. and Harry B. Helmsley Charitable Trust/ ; }, mesh = {Feasibility Studies ; *Enteral Nutrition ; Child ; Humans ; *Fecal Microbiota Transplantation ; Remission Induction ; RNA, Ribosomal, 16S/genetics ; Crohn Disease ; }, abstract = {BACKGROUND: Exclusive enteral nutrition (EEN) is a highly effective therapy for remission induction in pediatric Crohn's disease (CD), but relapse rates after return to a regular diet are high. Autologous fecal microbiota transfer (FMT) using stool collected during EEN-induced clinical remission might represent a novel approach to maintaining the benefits of EEN.<br><br>METHODS: Pediatric CD patients provided fecal material at home, which was shipped at 4 &#xb0;C to an FMT laboratory for FMT capsule generation and extensive pathogen safety screening. The microbial community composition of samples taken before and after shipment and after encapsulation was characterized using 16S rRNA amplicon sequencing.<br><br>RESULTS: Seven pediatric patients provided fecal material for nine test runs after at least three weeks of nutritional therapy. FMT capsules were successfully generated in 6/8 deliveries, but stool weight and consistency varied widely. Transport and processing of fecal material into FMT capsules did not fundamentally change microbial composition, but microbial richness was <30 genera in 3/9 samples. Stool safety screening was positive for potential pathogens or drug resistance genes in 8/9 test runs.<br><br>CONCLUSIONS: A high pathogen burden, low-diversity microbiota, and practical deficiencies of EEN-conditioned fecal material might render autologous capsule-FMT an unsuitable approach as maintenance therapy for pediatric CD patients.}, }
@article {pmid37048642, year = {2023}, author = {Shaikh, SD and Sun, N and Canakis, A and Park, WY and Weber, HC}, title = {Irritable Bowel Syndrome and the Gut Microbiome: A Comprehensive Review.}, journal = {Journal of clinical medicine}, volume = {12}, number = {7}, pages = {}, pmid = {37048642}, issn = {2077-0383}, abstract = {Irritable Bowel Syndrome (IBS) is a functional disorder of the gastrointestinal tract characterized by abdominal pain and altered bowel habits. It has a prevalence of 10 to 25% in the United States and has a high disease burden, as evidenced by reduced quality of life, decreased work productivity and increased healthcare utilization and costs. IBS has been associated with several intra-intestinal and extra-intestinal conditions, including psychiatric comorbidities. Although the pathophysiology of IBS has not been fully elucidated, it involves dysregulation of communication between the brain and gut (brain-gut axis) which is associated with alterations in intestinal motility, gut permeability, visceral hypersensitivity and gut microbiota composition. The purpose of this article is to review the role the gut microbiota plays in the pathophysiology of IBS, understand factors that affect the gut microbiome and explore the microbiome as a target of treatment.}, }
@article {pmid37047094, year = {2023}, author = {Del Barrio, M and Lavín, L and Santos-Laso, &#xc1; and Arias-Loste, MT and Odriozola, A and Rodriguez-Duque, JC and Rivas, C and Iruzubieta, P and Crespo, J}, title = {Faecal Microbiota Transplantation, Paving the Way to Treat Non-Alcoholic Fatty Liver Disease.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047094}, issn = {1422-0067}, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Intestines ; *Microbiota ; Dysbiosis/therapy ; Liver ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent cause of chronic liver disease (CLD). Currently, the only therapeutic recommendation available is a lifestyle change. However, adherence to this approach is often difficult to guarantee. Alteration of the microbiota and an increase in intestinal permeability seem to be key in the development and progression of NAFLD. Therefore, the manipulation of microbiota seems to provide a promising therapeutic strategy. One way to do so is through faecal microbiota transplantation (FMT). Here, we summarize the key aspects of FMT, detail its current indications and highlight the most recent advances in NAFLD.}, }
@article {pmid37046762, year = {2023}, author = {Kiousi, DE and Kouroutzidou, AZ and Neanidis, K and Karavanis, E and Matthaios, D and Pappa, A and Galanis, A}, title = {The Role of the Gut Microbiome in Cancer Immunotherapy: Current Knowledge and Future Directions.}, journal = {Cancers}, volume = {15}, number = {7}, pages = {}, pmid = {37046762}, issn = {2072-6694}, support = {5047285//European Regional Development Fund/ ; }, abstract = {Cancer immunotherapy is a treatment modality that aims to stimulate the anti-tumor immunity of the host to elicit favorable clinical outcomes. Immune checkpoint inhibitors (ICIs) gained traction due to the lasting effects and better tolerance in patients carrying solid tumors in comparison to conventional treatment. However, a significant portion of patients may present primary or acquired resistance (non-responders), and thus, they may have limited therapeutic outcomes. Resistance to ICIs can be derived from host-related, tumor-intrinsic, or environmental factors. Recent studies suggest a correlation of gut microbiota with resistance and response to immunotherapy as well as with the incidence of adverse events. Currently, preclinical and clinical studies aim to elucidate the unique microbial signatures related to ICI response and anti-tumor immunity, employing metagenomics and/or multi-omics. Decoding this complex relationship can provide the basis for manipulating the malleable structure of the gut microbiota to enhance therapeutic success. Here, we delve into the factors affecting resistance to ICIs, focusing on the intricate gut microbiome-immunity interplay. Additionally, we review clinical studies and discuss future trends and directions in this promising field.}, }
@article {pmid37046603, year = {2023}, author = {Yang, Q and Wei, Y and Zhu, Y and Guo, J and Zhang, J and He, Y and Li, X and Liu, J and Zhou, W}, title = {The Interaction between Gut Microbiota and Host Amino Acids Metabolism in Multiple Myeloma.}, journal = {Cancers}, volume = {15}, number = {7}, pages = {}, pmid = {37046603}, issn = {2072-6694}, abstract = {Although novel therapies have dramatically improved outcomes for multiple myeloma (MM) patients, relapse is inevitable and overall outcomes are heterogeneous. The gut microbiota is becoming increasingly recognized for its influence on host metabolism. To date, evidence has suggested that the gut microbiota contributes to MM, not only via the progressive activities of specific bacteria but also through the influence of the microbiota on host metabolism. Importantly, the abnormal amino acid metabolism, as well as the altered microbiome in MM, is becoming increasingly apparent, as is the influence on MM progression and the therapeutic response. Moreover, the gut-microbiota-host-amino-acid metabolism interaction in the progression of MM has been highlighted. Modulation of the gut microbiota (such as fecal microbiota transplantation, FMT) can be modified, representing a new angle in MM treatment that can improve outcomes. In this review, the relationship between gut microbiota, metabolism, and MM, together with strategies to modulate the microbiota, will be discussed, and some unanswered questions for ongoing and future research will be presented.}, }
@article {pmid37041839, year = {2023}, author = {Syafruddin, S and Siregar, TN and Wahyuni, S and Gholib, G and Pulungan, ILC and Muchsalmina, M}, title = {Transplantation of Aceh cattle ovary into the uterus of pseudopregnant local rabbits: Effect of post-transplant stress on uterine histopathology and ovarian follicle dynamics.}, journal = {Veterinary world}, volume = {16}, number = {3}, pages = {500-508}, pmid = {37041839}, issn = {0972-8988}, abstract = {BACKGROUND AND AIM: The increase in the levels of the cortisol hormone caused by the stress conditions generated by an ovary transplantation procedure can damage the uterus of the transplant recipient as well as the transplanted ovaries. This study aimed to analyze the histopathological changes that occur in the uterine horn of pseudopregnant local rabbits (recipients), as well as the ovarian follicular integrity of the donor Aceh cattle after transplantation.<br><br>MATERIALS AND METHODS: After 30 days of adaptation, all rabbits were divided into three treatment groups: R1 (the group of rabbits that underwent ovarian transplantation for 3 days, n = 5), R2 (the group of rabbits that underwent ovarian transplantation for 5 days, n = 5), and R3 (the group of rabbits that underwent ovarian transplantation for 7 days, n = 5). Pseudopregnancy induction was performed using the pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) methods. The rabbits were injected with 100 IU of PMSG intramuscularly, followed by an injection of 75 IU of hCG intravenously 3 days later. Ovarian transplantation was performed on day 8 (day 0 was the day of hCG injection). The concentration of cortisol hormone metabolites was measured from fecal samples using an enzyme-linked immunosorbent assay technique. The uterus and ovaries were collected for histopathological and follicular dynamics examination after the transplantation process was completed.<br><br>RESULTS: The mean cortisol levels (ng/g) recorded before versus after the transplant in the R1, R2, and R3 groups were 146.23 &#xb1; 17.60 versus 338.84 &#xb1; 302.79, 128.97 &#xb1; 81.56 versus 174.79 &#xb1; 101.70, and 124.88 &#xb1; 43.61 versus 321.91 &#xb1; 221.63 (p < 0.05), respectively. The examination of the histopathological appearance of the uterus revealed edema in the uterine lumen, hyperemia and hemorrhage in the endometrium, necrosis of the epithelium, and infiltration of inflammatory cells. Hemorrhage and hyperemia were severe and filled the endometrium in the R1 compared with the R2 and R3 animals. Ovarian follicle development occurred in all treatment groups, although some histopathological features were observed. The number of tertiary follicles in R1, R2, and R3 animals was 24.67 &#xb1; 7.37, 20.67 &#xb1; 7.57, and 9.67 &#xb1; 3.79 (p < 0.05), respectively.<br><br>CONCLUSION: Based on the results of this study, it can be concluded that the transplantation of ovaries from Aceh cattle into pseudopregnant local rabbits triggered an increase in the levels of the cortisol hormone and uterine histological changes; however, follicles were still detected at various stages of development in the transplanted Aceh cattle ovaries. The results of this study are valuable for clinicians and researchers because they provide information regarding an alternative in vivo ovarian preservation technique using pseudopregnant rabbits.}, }
@article {pmid37039469, year = {2023}, author = {Luo, ZB and Han, S and Yin, XJ and Liu, H and Wang, J and Xuan, M and Hao, C and Wang, D and Liu, Y and Chang, S and Li, D and Gao, K and Li, H and Quan, B and Quan, LH and Kang, JD}, title = {Fecal transplant from myostatin deletion pigs positively impacts the gut-muscle axis.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37039469}, issn = {2050-084X}, mesh = {Animals ; Mice ; Swine ; *Fecal Microbiota Transplantation ; *Myostatin/genetics/metabolism ; Muscle, Skeletal/metabolism ; }, abstract = {The host genome may influence the composition of the intestinal microbiota, and the intestinal microbiota has a significant effect on muscle growth and development. In this study, we found that the deletion of the myostatin (MSTN) gene positively regulates the expression of the intestinal tight junction-related genes TJP1 and OCLN through the myosin light-chain kinase/myosin light chain pathway. The intestinal structure of MSTN[-/-] pigs differed from wild-type, including by the presence of a thicker muscularis and longer plicae. Together, these changes affect the structure of intestinal microbiota. Mice transplanted with the intestinal microbiota of MSTN[-/-] pigs had myofibers with larger cross-sectional areas and higher fast-twitch glycolytic muscle mass. Microbes responsible for the production of short-chain fatty acids (SCFAs) were enriched in both the MSTN[-/-] pigs and recipient mice, and SCFAs levels were elevated in the colon contents. We also demonstrated that valeric acid stimulates type IIb myofiber growth by activating the Akt/mTOR pathway via G protein-coupled receptor 43 and ameliorates dexamethasone-induced muscle atrophy. This is the first study to identify the MSTN gene-gut microbiota-SCFA axis and its regulatory role in fast-twitch glycolytic muscle growth.}, }
@article {pmid37036515, year = {2023}, author = {Liu, J and Chen, H and Yu, T and Fu, X and Qian, C and Feng, X}, title = {Berberine mitigates intracerebral hemorrhage-induced neuroinflammation in a gut microbiota-dependent manner in mice.}, journal = {Aging}, volume = {15}, number = {7}, pages = {2705-2720}, pmid = {37036515}, issn = {1945-4589}, mesh = {Mice ; Male ; Animals ; *Berberine/pharmacology/therapeutic use ; Neuroinflammatory Diseases ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Cerebral Hemorrhage/complications/metabolism ; }, abstract = {BACKGROUND: Neuroinflammation is a frequent cause of brain damage after intracerebral hemorrhage (ICH). Gut microbiota are reported to regulate neuroinflammation. Berberine has been found to have anti-inflammatory actions, including in the central nervous system. However, it is not known whether berberine regulates neuroinflammation after ICH, nor is the relationship between the antineuroinflammatory actions of berberine and the gut microbiota after ICH understood.<br><br>METHODS: ICH was induced in male mice by collagenase injection. Immunofluorescent staining and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect microglia/macrophage phenotypes. Immunofluorescent staining, ELISA, and FITC-dextran were conducted to determine gut function. 16S rRNA sequencing of the fecal material was conducted to determine alterations in the gut microbiota. Antibiotic cocktail treatment and fecal microbiota transplantation (FMT) were used to deplete or restore the gut microbiota, respectively. Cylinder, forelimb placement and wire hanging tests were conducted to evaluate neurobehavioral function.<br><br>RESULTS: Berberine significantly reduced neuroinflammation and alleviated neurological dysfunction by preventing microglial/macrophage proinflammatory polarization in ICH mice. Berberine also enhanced the function of the intestinal barrier, as shown by reductions in the levels of lipopolysaccharide-binding protein. Neuroinflammation in ICH mice was markedly reduced after transplantation of microbiota from berberine-treated mice, similar to treatment with oral berberine. In addition, a reduction in the microbiota reversed the neuroprotective effect of berberine.<br><br>CONCLUSIONS: Berberine is a potential treatment for ICH-induced neuroinflammation, and its effects are at least partially dependent on the gut microbiota.}, }
@article {pmid37030333, year = {2023}, author = {Liu, Y and Li, J and Kang, W and Liu, S and Liu, J and Shi, M and Wang, Y and Liu, X and Chen, X and Huang, K}, title = {Aflatoxin B1 induces liver injury by disturbing gut microbiota-bile acid-FXR axis in mice.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {176}, number = {}, pages = {113751}, doi = {10.1016/j.fct.2023.113751}, pmid = {37030333}, issn = {1873-6351}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Aflatoxin B1/toxicity/metabolism ; Bile Acids and Salts/metabolism ; *Chemical and Drug Induced Liver Injury, Chronic/metabolism ; Liver/metabolism ; Inflammation/metabolism ; Mice, Inbred C57BL ; }, abstract = {Aflatoxin B1 (AFB1) is one of major pollutant in food and feed worldwide. The purpose of this study is to investigate the mechanism of AFB1-induced liver injury. Our results showed that AFB1 caused hepatic bile duct proliferation, oxidative stress, inflammation and liver injury in mice. AFB1 exposure induced gut microbiota dysbiosis and reduced fecal bile salt hydrolase (BSH) activity. AFB1 exposure promoted hepatic bile acid (BA) synthesis and changed intestinal BA metabolism, especially increased intestinal conjugated bile acids levels. AFB1 exposure inhibited intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF-15) signaling. Furthermore, the mice received fecal microbiota transplantation from AFB1-treated mice induced liver injury, reduced intestinal FXR signaling and increased hepatic BA synthesis. Finally, the intestine-restricted FXR agonist treatment decreased hepatic BA synthesis, ROS level, inflammation and liver injury in AFB1-treated mice. This study suggests that modifying the gut microbiota, altering intestinal BA metabolism and/or activating intestinal FXR/FGF-15 signaling may be of value for the treatment of AFB1-induced liver disease.}, }
@article {pmid37029815, year = {2023}, author = {Shatila, M and Ma, W and Cui, Y and Naz, S and S Thomas, A and N De Toni, E and Török, HP and Khaled, NB and Altan, M and Schneider, B and Wang, Y}, title = {Effects of immunosuppressive treatment on patient outcomes after immune checkpoint inhibitor-related gastrointestinal toxicity.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {10}, pages = {7793-7803}, pmid = {37029815}, issn = {1432-1335}, mesh = {Humans ; Immune Checkpoint Inhibitors/adverse effects ; Immunosuppressive Agents/adverse effects ; *Neoplasms/therapy ; *Colitis/chemically induced/drug therapy ; Progression-Free Survival ; Retrospective Studies ; }, abstract = {PURPOSE: Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of certain cancers but cause immune-related adverse events (irAEs). Gastrointestinal irAEs may necessitate extended periods of steroid use and the initiation of selective immunosuppressive therapy (SIT) which could theoretically counteract the effect of ICIs. In this study, we aim to explore the impact of immunosuppression use and duration on cancer progression and progression-free survival (PFS).<br><br>METHODS: This is a single-center retrospective review exploring cancer outcomes in patients taking ICIs who developed gastrointestinal irAEs within 1&#xa0;year of ICI initiation. Cancer outcome and progression free survival (PFS) were measured and compared by using IBM SPSS Statistics 26.<br><br>RESULTS: Of the 116 patients included in this study, 69 received immunosuppression to treat irAEs. The occurrence of colitis and use of immunosuppression for colitis were associated with less cancer progression by later assessment (p&#x2009;<&#x2009;0.05). Shorter durations of steroids with or without SIT for colitis were associated with less cancer progression within the study window than no immunosuppression (p&#x2009;<&#x2009;0.05). Immunosuppression has no effect on PFS (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: Our study reported shorter duration of steroid treatment for colitis may be associated with less cancer progression. Though the use of immunosuppression was not found to impact PFS, this may be confounded by the presence of colitis, which is known to improve cancer outcomes and could mask any negative impact of immunosuppression on survival. It may be preferable to limit long-term immunosuppression in the treatment of immune-mediated colitis to minimize potential complications. Prospective studies are needed to clarify this relationship, and treatments that abrogate the need for immunosuppression in these patients such as fecal microbiota transplantation.}, }
@article {pmid37022735, year = {2023}, author = {Pietras, EM}, title = {Young bugs rejuvenate old blood.}, journal = {Blood}, volume = {141}, number = {14}, pages = {1650-1652}, doi = {10.1182/blood.2023019638}, pmid = {37022735}, issn = {1528-0020}, mesh = {Animals ; Mice ; *Fecal Microbiota Transplantation ; *Hematopoietic Stem Cells ; Inflammation ; }, }
@article {pmid37022171, year = {2023}, author = {Hankir, MK and Kovatcheva-Datchary, P and Springer, R and Hoffmann, A and Vogel, J and Seyfried, F and Arora, T}, title = {Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0510922}, pmid = {37022171}, issn = {2165-0497}, mesh = {Firmicutes ; Rats, Zucker ; *Gastric Bypass ; Mice ; Animals ; Rats ; *Obesity, Morbid/microbiology ; Obesity/surgery ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Weight Loss ; *Diabetes Mellitus, Type 2/therapy/microbiology ; }, abstract = {Roux-en-Y gastric bypass surgery (RYGB) leads to improved glycemic control in individuals with severe obesity beyond the effects of weight loss alone. Here, We addressed the potential contribution of gut microbiota in mediating this favourable surgical outcome by using an established preclinical model of RYGB. 16S rRNA sequencing revealed that RYGB-treated Zucker fatty rats had altered fecal composition of various bacteria at the phylum and species levels, including lower fecal abundance of an unidentified Erysipelotrichaceae species, compared with both sham-operated (Sham) and body weight-matched to RYGB-treated (BWM) rats. Correlation analysis further revealed that fecal abundance of this unidentified Erysipelotrichaceae species linked with multiple indices of glycemic control uniquely in RYGB-treated rats. Sequence alignment of this Erysipelotrichaceae species identified Longibaculum muris to be the most closely related species, and its fecal abundance positively correlated with oral glucose intolerance in RYGB-treated rats. In fecal microbiota transplant experiments, the improved oral glucose tolerance of RYGB-treated compared with BWM rats could partially be transferred to recipient germfree mice, independently of body weight. Unexpectedly, providing L. muris as a supplement to RYGB recipient mice further improved oral glucose tolerance, while administering L. muris alone to chow-fed or Western style diet-challenged conventionally raised mice had minimal metabolic impact. Taken together, our findings provide evidence that the gut microbiota contributes to weight loss-independent improvements in glycemic control after RYGB and demonstrate how correlation of a specific gut microbiota species with a host metabolic trait does not imply causation. IMPORTANCE Metabolic surgery remains the most effective treatment modality for severe obesity and its comorbidities, including type 2 diabetes. Roux-en-Y gastric bypass (RYGB) is a commonly performed type of metabolic surgery that reconfigures gastrointestinal anatomy and profoundly remodels the gut microbiota. While it is clear that RYGB is superior to dieting when it comes to improving glycemic control, the extent to which the gut microbiota contributes to this effect remains untested. In the present study, we uniquely linked fecal Erysipelotrichaceae species, including Longibaculum muris, with indices of glycemic control after RYGB in genetically obese and glucose-intolerant rats. We further show that the weight loss-independent improvements in glycemic control in RYGB-treated rats can be transmitted via their gut microbiota to germfree mice. Our findings provide rare causal evidence that the gut microbiota contributes to the health benefits of metabolic surgery and have implications for the development of gut microbiota-based treatments for type 2 diabetes.}, }
@article {pmid37020579, year = {2023}, author = {Di Pietro, R and Arroyo, LG and Leclere, M and Costa, M}, title = {Effects of concentrated fecal microbiota transplant on the equine fecal microbiota after antibiotic-induced dysbiosis.}, journal = {Canadian journal of veterinary research = Revue canadienne de recherche veterinaire}, volume = {87}, number = {2}, pages = {85-96}, pmid = {37020579}, issn = {1928-9022}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects ; Bacteria/isolation &amp; purification ; *Dysbiosis/chemically induced/therapy/veterinary ; *Fecal Microbiota Transplantation/methods/veterinary ; Feces/microbiology ; *Horse Diseases/chemically induced/therapy ; Horses ; Treatment Outcome ; Gastrointestinal Microbiome ; }, abstract = {Bacterial imbalances are observed in intestinal diseases and fecal microbiota transplantation (FMT) has been used to restore the intestinal microbiota of horses. However, there is evidence that the current methods proposed for FMT in horses have limited efficacy. The objective of this study was to concentrate the bacteria present in the donor stool by centrifugation, and to test the effect in horses with antibiotic-induced dysbiosis. One healthy 11-year-old horse was selected as a fecal donor and 9 horses were given trimethoprim sulfadiazine (TMS) for 5 days to induce dysbiosis. Horses received either a concentrated FMT (cFMT, n = 3), fresh unconcentrated FMT (fFMT, n = 3), or 10% glycerol solution (vehicle, VEH, n = 3) by nasogastric tube for 3 days. Fecal samples were collected on Days 0, 4, 9, 11, and 21 for microbiota analysis (Illumina sequencing). The TMS significantly changed the bacterial composition of horses' feces (D0 versus D4). The composition of the cFMT and fFMT recipient horses was significantly different after transplantation compared to after antibiotic-induced dysbiosis (D4 versus D11), whereas the microbiota of the vehicle recipients was not, indicating that both protocols induced transient changes. However, preparation of FMT solutions markedly changed the original composition present in the donor's feces, with significant enrichment of Escherichia genus in the cFMT. Individual susceptibility to restoration of the microbiota was observed in horses, similar to what is known for other species. Our results suggest that concentrating bacteria should not be recommended in preparation of FMT solutions and that further research is required to improve current methods recommended to perform FMT in horses.}, }
@article {pmid37019989, year = {2023}, author = {Nemoto, S and Kubota, T and Ohno, H}, title = {Exploring body weight-influencing gut microbiota by elucidating the association with diet and host gene expression.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {5593}, pmid = {37019989}, issn = {2045-2322}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Obesity/metabolism ; Weight Gain ; Diet, High-Fat ; Gene Expression ; *Insulins ; Mice, Inbred C57BL ; }, abstract = {We aimed to identify gut microbiota that influences body weight by elucidating the association with diets and host genes. Germ-free (GF) mice with and without fecal microbiota transplant (FMT) were fed a normal, high-carbohydrate, or high-fat diet. FMT mice exhibited greater total body weight; adipose tissue and liver weights; blood glucose, insulin, and total cholesterol levels; and oil droplet size than the GF mice, regardless of diet. However, the extent of weight gain and metabolic parameter levels associated with gut microbiota depended on the nutrients ingested. For example, a disaccharide- or polysaccharide-rich diet caused more weight gain than a monosaccharide-rich diet. An unsaturated fatty acid-rich diet had a greater microbial insulin-increasing effect than a saturated fatty acid-rich diet. Perhaps the difference in microbial metabolites produced from substances taken up by the host created metabolic differences. Therefore, we analyzed such dietary influences on gut microbiota, differentially expressed genes between GF and FMT mice, and metabolic factors, including body weight. The results revealed a correlation between increased weight gain, a fat-rich diet, increased Ruminococcaceae abundance, and decreased claudin 22 gene expression. These findings suggest that weight regulation might be possible through the manipulation of the gut microbiota metabolism using the host's diet.}, }
@article {pmid37019893, year = {2023}, author = {Panebianco, C and Pisati, F and Villani, A and Andolfo, A and Ulaszewska, M and Bellini, E and Ferro, C and Lombardi, R and Orsenigo, F and Latiano, TP and Belmonte, B and Tripodo, C and Perri, F and Pazienza, V}, title = {Counteracting gemcitabine+nab-paclitaxel induced dysbiosis in KRAS wild type and KRAS[G12D] mutated pancreatic cancer in vivo model.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {116}, pmid = {37019893}, issn = {2058-7716}, support = {IG 2019 - ID. 23006 project//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; Ricerca Corrente Program 2022-2024//Ministero della Salute (Ministry of Health, Italy)/ ; }, abstract = {Pancreatic cancer (PC) has a very low survival rate mainly due to late diagnosis and refractoriness to therapies. The latter also cause adverse effects negatively affecting the patients' quality of life, often requiring dose reduction or discontinuation of scheduled treatments, compromising the chances of cure. We explored the effects of a specific probiotic blend on PC mice xenografted with KRAS wild-type or KRASG12D mutated cell lines alone or together with gemcitabine+nab-paclitaxel treatment to then assess tumor volume and clinical pathological variables. Beside a semi-quantitative histopathological evaluation of murine tumor and large intestine samples, histochemical and immunohistochemical analyses were carried out to evaluate collagen deposition, proliferation index Ki67, immunological microenvironment tumor-associated, DNA damage markers and also mucin production. Blood cellular and biochemical parameters and serum metabolomics were further analyzed. 16S sequencing was performed to analyze the composition of fecal microbiota. Gemcitabine+nab-paclitaxel treatment impaired gut microbial profile in KRAS wild-type and KRASG12D mice. Counteracting gemcitabine+nab-paclitaxel- induced dysbiosis through the administration of probiotics ameliorated chemotherapy side effects and decreased cancer-associated stromatogenesis. Milder intestinal damage and improved blood count were also observed upon probiotics treatment as well as a positive effect on fecal microbiota, yielding an increase in species richness and in short chain fatty acids producing- bacteria. Mice' serum metabolomic profiles revealed significant drops in many amino acids upon probiotics administration in KRAS wild-type mice while in animals transplanted with PANC-1 KRASG12D mutated all treated groups showed a sharp decline in serum levels of bile acids with respect to control mice. These results suggest that counteracting gemcitabine+nab-paclitaxel-induced dysbiosis ameliorates chemotherapy side effects by restoring a favorable microbiota composition. Relieving adverse effects of the chemotherapy through microbiota manipulation could be a desirable strategy in order to improve pancreatic cancer patients' quality of life and to increase the chance of cure.}, }
@article {pmid37019665, year = {2023}, author = {Ka, Y and Ito, R and Nozu, R and Tomiyama, K and Ueno, M and Ogura, T and Takahashi, R}, title = {Establishment of a human microbiome- and immune system-reconstituted dual-humanized mouse model.}, journal = {Experimental animals}, volume = {72}, number = {3}, pages = {402-412}, pmid = {37019665}, issn = {1881-7122}, mesh = {Mice ; Animals ; Humans ; Mice, Inbred NOD ; *Immune System ; Hematopoietic Stem Cells ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Mice, SCID ; }, abstract = {Humanized mice are widely used to study the human immune system in vivo and investigate therapeutic targets for various human diseases. Immunodeficient NOD/Shi-scid-IL2rγ[null] (NOG) mice transferred with human hematopoietic stem cells are a useful model for studying human immune systems and analyzing engrafted human immune cells. The gut microbiota plays a significant role in the development and function of immune cells and the maintenance of immune homeostasis; however, there is currently no available animal model that has been reconstituted with human gut microbiota and immune systems in vivo. In this study, we established a new model of CD34[+] cell-transferred humanized germ-free NOG mice using an aseptic method. Flow cytometric analysis revealed that the germ-free humanized mice exhibited a lower level of human CD3[+] T cells than the SPF humanized mice. Additionally, we found that the human CD3[+] T cells slightly increased after transplanting human gut microbiota into the germ-free humanized mice, suggesting that the human microbiota supports T cell proliferation or maintenance in humanized mice colonized by the gut microbiota. Consequently, the dual-humanized mice may be useful for investigating the physiological role of the gut microbiota in human immunity in vivo and for application as a new humanized mouse model in cancer immunology.}, }
@article {pmid37012144, year = {2023}, author = {Emile, SH and Garoufalia, Z and Barsom, S and Horesh, N and Gefen, R and Zhou, P and Wexner, SD}, title = {Systematic review and meta-analysis of randomized clinical trials on the treatment of low anterior resection syndrome.}, journal = {Surgery}, volume = {173}, number = {6}, pages = {1352-1358}, doi = {10.1016/j.surg.2023.02.010}, pmid = {37012144}, issn = {1532-7361}, mesh = {Humans ; *Low Anterior Resection Syndrome ; Postoperative Complications/etiology/therapy ; *Rectal Neoplasms ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: We conducted a systematic review of randomized clinical trials on treating low anterior resection syndrome to help inform current practice.<br><br>METHODS: This Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of randomized clinical trials involved different treatments for low anterior resection syndrome. The risk of bias 2 tool was used to assess the risk of bias. The main outcomes were improvement in low anterior resection syndrome after treatment assessed by change in low anterior resection syndrome, fecal incontinence scores, and adverse treatment effects.<br><br>RESULTS: After an initial screening of 1,286 studies, 7 randomized clinical trials were included. Sample sizes ranged between 12 to 104 patients. Posterior tibial nerve stimulation was the most frequently assessed treatment in 3 randomized clinical trials. The weighted mean difference between posterior tibial nerve stimulation and medical treatment or sham therapy in follow-up low anterior resection syndrome score (-3.31, P&#xa0;= .157) was insignificant. Transanal irrigation reduced major low anterior resection syndrome symptoms by 61.5% compared with 28.6% after posterior tibial nerve stimulation with a significantly lower 6-month follow-up low anterior resection syndrome score. Pelvic floor training achieved better improvement in low anterior resection syndrome than standard care (47.8% vs 21.3%) at 6 months, but this was not maintained at 12 months (40.0% vs 34.9%). Ramosetron was associated with a greater short-term improvement in major low anterior resection syndrome (23% vs 8%) and a lower low anterior resection syndrome score (29.5 vs 34.6) at 4-weeks follow-up than Kegels or Sitz baths. No significant improvement in bowel function was noted after probiotics use as probiotics and placebo had similar follow-up low anterior resection syndrome scores (33.3 vs 36).<br><br>CONCLUSION: Transanal irrigation was associated with improvement in low anterior resection syndrome according to 2 trials, and ramosetron showed promising short-term results in one trial. Posterior tibial nerve stimulation had a marginal benefit compared with standard care. In contrast, pelvic floor training was associated with short-term symptomatic improvement, and probiotics showed no tangible improvement in low anterior resection syndrome symptoms. Firm conclusions cannot be drawn due to the small number of trials published.}, }
@article {pmid37011727, year = {2023}, author = {Gharaie, S and Lee, K and Newman-Rivera, AM and Xu, J and Patel, SK and Gooya, M and Arend, LJ and Raj, DS and Pluznick, J and Parikh, C and Noel, S and Rabb, H}, title = {Microbiome modulation after severe acute kidney injury accelerates functional recovery and decreases kidney fibrosis.}, journal = {Kidney international}, volume = {104}, number = {3}, pages = {470-491}, doi = {10.1016/j.kint.2023.03.024}, pmid = {37011727}, issn = {1523-1755}, support = {R01 DK123342/DK/NIDDK NIH HHS/United States ; R01 DK104662/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Acute Kidney Injury/chemically induced ; Kidney/pathology ; *Reperfusion Injury/pathology ; Ischemia ; Fibrosis ; *Microbiota ; Amoxicillin/adverse effects ; }, abstract = {Targeting gut microbiota has shown promise to prevent experimental acute kidney injury (AKI). However, this has not been studied in relation to accelerating recovery and preventing fibrosis. Here, we found that modifying gut microbiota with an antibiotic administered after severe ischemic kidney injury in mice, particularly with amoxicillin, accelerated recovery. These indices of recovery included increased glomerular filtration rate, diminution of kidney fibrosis, and reduction of kidney profibrotic gene expression. Amoxicillin was found to increase stool Alistipes, Odoribacter and Stomatobaculum species while significantly depleting Holdemanella and Anaeroplasma. Specifically, amoxicillin treatment reduced kidney CD4[+]T cells, interleukin (IL)-17 [+]CD4[+]T cells, and tumor necrosis factor-α double negative T cells while it increased CD8[+]T cells and PD1[+]CD8[+]T cells. Amoxicillin also increased gut lamina propria CD4[+]T cells while decreasing CD8[+]T and IL-17[+]CD4[+]T cells. Amoxicillin did not accelerate repair in germ-free or CD8-deficient mice, demonstrating microbiome and CD8[+]T lymphocytes dependence for amoxicillin protective effects. However, amoxicillin remained effective in CD4-deficient mice. Fecal microbiota transplantation from amoxicillin-treated to germ-free mice reduced kidney fibrosis and increased Foxp3[+]CD8[+]T cells. Amoxicillin pre-treatment protected mice against kidney bilateral ischemia reperfusion injury but not cisplatin-induced AKI. Thus, modification of gut bacteria with amoxicillin after severe ischemic AKI is a promising novel therapeutic approach to accelerate recovery of kidney function and mitigate the progression of AKI to chronic kidney disease.}, }
@article {pmid37010964, year = {2023}, author = {Klingensmith, NJ and Coopersmith, CM}, title = {Gut Microbiome in Sepsis.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {250-257}, pmid = {37010964}, issn = {1557-8674}, support = {R01 GM072808/GM/NIGMS NIH HHS/United States ; R01 GM104323/GM/NIGMS NIH HHS/United States ; R35 GM148217/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Intestinal Mucosa/microbiology ; *Probiotics ; Prebiotics ; Bacteria ; *Sepsis/therapy ; }, abstract = {Abstract The gut has been hypothesized to be the "motor" of multiple organ dysfunction in sepsis. Although there are multiple ways in which the gut can drive systemic inflammation, increasing evidence suggests that the intestinal microbiome plays a more substantial role than previously appreciated. An English language literature review was performed to summarize the current knowledge of sepsis-induced gut microbiome dysbiosis. Conversion of a normal microbiome to a pathobiome in the setting of sepsis is associated with worsened mortality. Changes in microbiome composition and diversity signal the intestinal epithelium and immune system resulting in increased intestinal permeability and a dysregulated immune response to sepsis. Clinical approaches to return to microbiome homeostasis may be theoretically possible through a variety of methods including probiotics, prebiotics, fecal microbial transplant, and selective decontamination of the digestive tract. However, more research is required to determine the efficacy (if any) of targeting the microbiome for therapeutic gain. The gut microbiome rapidly loses diversity with emergence of virulent bacteria in sepsis. Restoring normal commensal bacterial diversity through various therapies may be an avenue to improve sepsis mortality.}, }
@article {pmid37010962, year = {2023}, author = {Gibson, GA and Owen, EJ}, title = {Non-Antibiotic Approaches to Infection that Preserve the Microbiome in Critically Ill Patients.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {284-291}, doi = {10.1089/sur.2023.020}, pmid = {37010962}, issn = {1557-8674}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use ; Critical Illness/therapy ; Dysbiosis/therapy ; *Microbiota ; Gastrointestinal Tract ; }, abstract = {In critically ill patients, the gut microbiota is subjected to various factors including antimicrobial exposure, modified gastrointestinal transit, nutrition support, as well as infection, which may lead to dysbiosis during the intensive care unit and hospital stay. Dysbiosis occupies an increasingly important role in driving morbidity and perhaps mortality in the critically ill or injured. Given that antibiotics lead to dysbiosis, it is relevant to understand the range of non-antibiotic approaches to infection-including those related to multi-drug-resistant organisms-that may leave the microbiome unimpacted. These strategies most prominently include the elimination of unabsorbed antibiotic agents from the digestive tract, pro-/pre-/synbiotics, fecal microbiota transplant, selective digestive and oropharyngeal decontamination, phage therapy, anti-sense oligonucleotides, structurally nanoengineered antimicrobial peptide polymers, and vitamin C-based lipid nanoparticles for adoptive macrophage transfer. Herein, we review the rationale for these therapies, current data regarding their use in critically ill patients, and the therapeutic potential for strategies that are not yet deployed in human medical care.}, }
@article {pmid37010243, year = {2023}, author = {}, title = {Corrigendum: Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion.}, journal = {Chinese medical journal}, volume = {136}, number = {8}, pages = {1008}, pmid = {37010243}, issn = {2542-5641}, }
@article {pmid37009327, year = {2023}, author = {Jeyaraman, M and Nallakumarasamy, A and Jain, VK}, title = {Gut Microbiome - Should we treat the gut and not the bones?.}, journal = {Journal of clinical orthopaedics and trauma}, volume = {39}, number = {}, pages = {102149}, pmid = {37009327}, issn = {0976-5662}, abstract = {Gut microbiome (GM) forms an integral part of homeostasis of an individual. Due to the recent development of metagenomics, the plausibility of sequencing GM and its therapeutic ability for various diseases has been explored. Dysbiosis or disequilibrium or pertubations of GM leads to disruption of intercommunication signaling among gut-bone axis, gut-bone-brain axis, and gut-disc axis resulting in the progression of various chronic diseases. The therapeutic interventions to restore the GM like prebiotics and probiotics, bacteriophage therapy, fecal microbiota transplantation, and physical biomodulation have been identified. This review throw the lime light on the effect of gut dysbiosis in musculoskeletal diseases.}, }
@article {pmid37008345, year = {2023}, author = {Larsen, C and Andersen, AB and Sato, H and Brunse, A and Thymann, T}, title = {Transplantation of fecal filtrate to neonatal pigs reduces post-weaning diarrhea: A pilot study.}, journal = {Frontiers in veterinary science}, volume = {10}, number = {}, pages = {1110128}, pmid = {37008345}, issn = {2297-1769}, abstract = {Post-weaning diarrhea (PWD) remains a major source of mortality and morbidity in swine production. Transplantation of bacteria-free filtrate of feces (fecal filtrate transplant, FFT) has shown gut protective effects in neonatal pigs, and early postnatal establishment of the gut microbiome is suggested to determine later stability and robustness of the gut. We, therefore, hypothesized that early postnatal transplantation of bacteria-free feces would have a protective effect against PWD. Using fecal filtrates derived from healthy lactating sows, we compared oral administration of fecal filtrate transplantation (FFT, n = 20) and saline (CON, n = 18) in newborn piglets. We assessed growth, diarrhea prevalence, blood parameters, organ measurements, morphology, and gut brush border enzymes and analyzed luminal bacterial composition using 16S rRNA gene amplicon sequencing. The two groups showed similar average daily gain (ADG) during the suckling period, whereas in the post-weaning period, a negative ADG was observed in both groups. While diarrhea was largely absent in both groups before weaning, there was a lower diarrhea prevalence on days 27 (p = 2.07[*]10[-9]), 28 (p = 0.04), and 35 (p = 0.04) in the FFT group relative to CON. At weaning on day 27, the FFT group had higher numbers of red blood cells, monocytes, and lymphocytes, while on day 35, i.e., 1 week after weaning, the two groups were similar regarding hematology. The biochemical profile was largely similar between FFT and CON on days 27 and 35, except for a higher level of alanine aminotransferase and a lower level of Mg in the FFT group. Likewise, organ weights relative to body weight were largely similar on day 35, albeit with a lower stomach weight and more colon content in FFT relative to CON. Gut mucosal percentage and mucosal enzyme activity were similar between the two groups on days 27 and 35. Gut bacterial composition was slightly different on day 35 but not on day 27. In conclusion, early postnatal administration of FFT, showed positive clinical effects in post-weaning pigs, albeit with subtle effects on the gut mucosa and microbiome. Prophylactic treatment with FFT may offer a means to reduce morbidity, yet larger studies are required to document effect size.}, }
@article {pmid37005752, year = {2023}, author = {Gao, J and Chen, H and Xu, L and Li, S and Yan, H and Jiang, L and Cheng, W and Jiang, Z}, title = {Effects of Intestinal Microorganisms on Influenza-Infected Mice with Antibiotic-Induced Intestinal Dysbiosis, through the TLR7 Signaling Pathway.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {28}, number = {3}, pages = {43}, doi = {10.31083/j.fbl2803043}, pmid = {37005752}, issn = {2768-6698}, mesh = {Mice ; Animals ; Humans ; *Influenza, Human/complications ; *Orthomyxoviridae Infections/complications ; Myeloid Differentiation Factor 88/genetics/metabolism/pharmacology ; Toll-Like Receptor 7/genetics/metabolism ; Dysbiosis ; Signal Transduction ; NF-kappa B/metabolism ; Adaptor Proteins, Signal Transducing/metabolism ; Inflammation ; Intestines ; }, abstract = {BACKGROUND: Stability of intestinal flora is not only important for maintaining stable immune functions; it is also a key immune channel communicating the interaction between lung and intestine. In this study, probiotics and fecal microbiota transplantation (FMT) were used to regulate influenza-infected mice with antibiotic-induced intestinal dysbiosis and the effects of intestinal microorganisms on these mice were subsequently observed and evaluated.<br><br>METHODS: Mice are housed in a normal environment with intranasal infection with influenza virus (FM1). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine messenger RNA expression and lung viral replication of toll-like receptor 7 (TLR7), myeloid differentiation primary reaction 88 (MyD88) and nuclear factor &#x3ba;B (ss) p65 in the TLR7 signaling pathway. Western blotting is used to measure the expression levels of TLR7, MyD88, and NF-&#x3ba;B p65 proteins. Flow cytometry was used to detect the proportion of Th17/T regulated cells.<br><br>RESULTS: Results showed that compared with the simple virus group, both diversity and species of intestinal flora in influenza-infected mice with antibiotic-induced intestinal dysbiosis were lower, in vivo viral replication was significantly increased, lung and intestinal tissues were seriously damaged, degree of inflammation increased, expression of the TLR7 signaling pathway increased, and the Th1/Th2:Th17/Treg ratio decreased. Probiotics and FMT effectively regulated intestinal flora, improved pathological lung changes and inflammation caused by influenza infection, and adjusted the TLR7 signaling pathway and the Th1/Th2:Th17/Treg ratio. This effect was not obvious in TLR7-&#x2063;/- mice.In summary, by affecting the TLR7 signaling pathway, intestinal microorganisms reduced the inflammatory response in the lungs of influenza-infected mice with imbalances in antibiotic flora.<br><br>CONCLUSIONS: By affecting the TLR7 signaling pathway, intestinal microorganisms reduced the inflammatory response in the lungs of influenza-infected mice with imbalances in antibiotic flora. In summary, damage to lung tissue and intestinal mucosa in influenza-infected mice with antibiotic-induced intestinal dysbiosis is more serious compared to simple virus-infected mice. Improving intestinal flora using probiotics or FMT can alleviate intestinal inflammation and improve pulmonary inflammation through the TLR7 signaling pathway.}, }
@article {pmid37004699, year = {2023}, author = {He, Z and Liu, Y and Li, Z and Sun, T and Li, Z and Manyande, A and Xiang, H and Xiong, J}, title = {Gut microbiota regulates circadian oscillation in hepatic ischemia-reperfusion injury-induced cognitive impairment by interfering with hippocampal lipid metabolism in mice.}, journal = {Hepatology international}, volume = {17}, number = {6}, pages = {1645-1658}, pmid = {37004699}, issn = {1936-0541}, support = {81873467//National Natural Science Foundation of China/ ; 81670240//National Natural Science Foundation of China/ ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Lipid Metabolism ; *Liver Diseases/genetics ; *Reperfusion Injury/genetics/metabolism ; *Cognitive Dysfunction/etiology ; Hippocampus/metabolism ; Lipids ; }, abstract = {BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) is a common complication of liver surgery, which can lead to extrahepatic metabolic disorders, such as cognitive impairment. Recent observations have emphasized the critical effects of gut microbial metabolites in regulating the development of liver injury. Herein, we investigated the potential contribution of gut microbiota to HIRI-related cognitive impairment.<br><br>METHODS: HIRI murine models were established by ischemia-reperfusion surgery in the morning (ZT0, 08:00) and evening (ZT12, 20:00), respectively. Antibiotic-induced pseudo-germ-free mice were gavaged with fecal bacteria of the HIRI models. Behavioral test was used to assess cognitive function. 16S rRNA gene sequencing and metabolomics were used for microbial and hippocampal analysis.<br><br>RESULTS: Our results established that cognitive impairment caused by HIRI underwent diurnal oscillations; HIRI mice performed poorly on the Y-maze test and the novel object preference test when surgery occurred in the evening compared with the morning. In addition, fecal microbiota transplantation (FMT) from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior. The specific composition and metabolites of gut microbiota were analyzed between the ZT0-HIRI and ZT12-HIRI, and bioinformatic analysis showed that the differential fecal metabolites were significantly enriched in lipid metabolism pathways. After FMT, the hippocampal lipid metabolome between the P-ZT0-HIRI and P-ZT12-HIRI groups was analyzed to reveal a series of lipid molecules with significant differences.<br><br>CONCLUSIONS: Our findings indicate that gut microbiota are involved in circadian differences of HIRI-related cognitive impairment by affecting hippocampal lipid metabolism.}, }
@article {pmid37003055, year = {2023}, author = {Jamal, R and Messaoudene, M and de Figuieredo, M and Routy, B}, title = {Future indications and clinical management for fecal microbiota transplantation (FMT) in immuno-oncology.}, journal = {Seminars in immunology}, volume = {67}, number = {}, pages = {101754}, doi = {10.1016/j.smim.2023.101754}, pmid = {37003055}, issn = {1096-3618}, support = {//CIHR/Canada ; }, mesh = {Humans ; Animals ; Mice ; Fecal Microbiota Transplantation/adverse effects ; Immune Checkpoint Inhibitors ; Treatment Outcome ; *Microbiota ; *Neoplasms/therapy/etiology ; }, abstract = {The gut microbiota has rapidly emerged as one of the "hallmarks of cancers" and a key contributor to cancer immunotherapy. Metagenomics profiling has established the link between microbiota compositions and immune checkpoint inhibitors response and toxicity, while murine experiments demonstrating the synergistic benefits of microbiota modification with immune checkpoint inhibitors (ICIs) pave a clear path for translation. Fecal microbiota transplantation (FMT) is one of the most effective treatments for patients with Clostridioides difficile, but its utility in other disease contexts has been limited. Nonetheless, promising data from the first trials combining FMT with ICIs have provided strong clinical rationale to pursue this strategy as a novel therapeutic avenue. In addition to the safety considerations surrounding new and emerging pathogens potentially transmissible by FMT, several other challenges must be overcome in order to validate the use of FMT as a therapeutic option in oncology. In this review, we will explore how the lessons learned from FMT in other specialties will help shape the design and development of FMT in the immuno-oncology arena.}, }
@article {pmid37001978, year = {2024}, author = {Xu, Z and Mak, JWY and Lin, Y and Yang, K and Liu, Q and Zhang, F and Lau, L and Tang, W and Ching, JY and Tun, HM and Chan, P and Chan, FKL and Ng, SC}, title = {Mixed-donor faecal microbiota transplantation was associated with increased butyrate-producing bacteria for obesity.}, journal = {Gut}, volume = {73}, number = {5}, pages = {875-878}, doi = {10.1136/gutjnl-2022-328993}, pmid = {37001978}, issn = {1468-3288}, mesh = {Humans ; *Fecal Microbiota Transplantation ; Obesity/therapy ; *Microbiota ; Butyrates ; Bacteria ; Feces/microbiology ; }, }
@article {pmid37001737, year = {2023}, author = {Camilleri, M and Dilmaghani, S}, title = {Update on treatment of abdominal pain in irritable bowel syndrome: A narrative review.}, journal = {Pharmacology &amp; therapeutics}, volume = {245}, number = {}, pages = {108400}, doi = {10.1016/j.pharmthera.2023.108400}, pmid = {37001737}, issn = {1879-016X}, mesh = {Humans ; *Irritable Bowel Syndrome/chemically induced/drug therapy ; Fermentation ; Disaccharides/adverse effects ; Oligosaccharides/adverse effects ; Diet ; Abdominal Pain/therapy/chemically induced ; }, abstract = {The objectives of this narrative review are to update readers on the current state-of-the-art regarding diverse approaches for the treatment of pain, global symptoms, or adequate relief in irritable bowel syndrome (IBS). The article appraises medications, dietary interventions including low fermentable oligosaccharides, disaccharides, and monosaccharides and polyols (FODMAP) diet, fecal microbial transplantation (FMT), electrical approaches, and behavioral therapies including cognitive behavioral therapy (CBT), gut-directed hypnotherapy (GDH), mindfulness, and open-label placebo. Current evidence demonstrates only modest benefit in global IBS symptoms and pain relief. A future approach that identifies pathophysiological mechanisms of IBS through validated biomarkers has the potential to individualize treatment of patients rather than sequential therapeutic trial and error approaches.}, }
@article {pmid36997133, year = {2023}, author = {Li, MY and Wu, YZ and Qiu, JG and Lei, JX and Li, MX and Xu, N and Liu, YH and Jin, Z and Su, ZR and Lee, SM and Zheng, XB and Xiao-Qi, H}, title = {Huangqin Decoction ameliorates ulcerative colitis by regulating fatty acid metabolism to mediate macrophage polarization via activating FFAR4-AMPK-PPARα pathway.}, journal = {Journal of ethnopharmacology}, volume = {311}, number = {}, pages = {116430}, doi = {10.1016/j.jep.2023.116430}, pmid = {36997133}, issn = {1872-7573}, mesh = {Animals ; Mice ; PPAR alpha/genetics ; AMP-Activated Protein Kinases ; Scutellaria baicalensis ; *Colitis, Ulcerative/chemically induced/drug therapy ; Dextran Sulfate/toxicity ; RNA, Ribosomal, 16S ; Colon ; Disease Models, Animal ; Fatty Acids ; *Colitis ; Mice, Inbred C57BL ; }, abstract = {Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula chronicled in Shang Han Lun, is safe and effective for treatment of ulcerative colitis (UC).<br><br>AIM OF THE STUDY: To investigate the effect of HQD against dextran sulfate sodium (DSS)-induced UC mice by regulating gut microbiota and metabolites, and further explore the mechanism of fatty acid metabolism on macrophage polarization.<br><br>MATERIALS AND METHODS: Based on 3% dextran sulfate sodium (DSS)-induced UC mice model, clinical symptoms observation (body weight, DAI, and colon length) and histological inspection were used to evaluate the efficacy of HQD and fecal microbiota transplantation (FMT) from HQD-treated mice. The gut microbiota and metabolites were detected by 16S rRNA sequencing and metabolomics analysis. The parameters of fatty acid metabolism, macrophage polarization, and FFAR1/FFAR4-AMPK-PPAR&#x3b1; pathway were analyzed by immunofluorescence analysis, western blotting, and real-time PCR. Then, the effects of FFAR1 and FFAR4 on macrophage polarization were examined by agonists based on LPS-induced RAW264.7&#xa0;cell model.<br><br>RESULTS: The results showed that FMT, like HQD, ameliorated UC by improving weight loss, restoring colon length, and reducing DAI scores and histopathological scores. Besides, HQD and FMT both enhanced the richness of gut microbiota, and modulated intestinal bacteria and metabolites to achieve a new balance. Untargeted metabolomics analysis revealed that fatty acids, especially long-chain fatty acids (LCFAs), dominated in HQD against DSS-induced UC by regulating the gut microenvironment. Further, FMT and HQD recovered the expression of fatty acid metabolism-related enzymes, and simultaneously activated FFAR1/FFAR4-AMPK-PPAR&#x3b1; pathway but suppressed NF-&#x3ba;B pathway. Combined with cell experiment, HQD and FMT promoted macrophage polarization from M1 toward M2, which were well associated with anti-inflammatory cytokines and combined with the activated FFAR4.<br><br>CONCLUSIONS: The mechanism of HQD against UC was related to regulating fatty acid metabolism to mediate M2 macrophage polarization by activating the FFAR4-AMPK-PPAR&#x3b1; pathway.}, }
@article {pmid36996849, year = {2023}, author = {Zhang, Y and Sun, Y and Liu, Y and Liu, J and Sun, J and Liu, X and Fan, B and Lu, C and Wang, F}, title = {Polygonum sibiricum polysaccharides exert the antidepressant-like effects in chronic unpredictable mild stress-induced depressive mice by modulating microbiota-gut-brain axis.}, journal = {Phytotherapy research : PTR}, volume = {37}, number = {8}, pages = {3408-3423}, doi = {10.1002/ptr.7813}, pmid = {36996849}, issn = {1099-1573}, support = {CAAS-ASTIP-2023-IFST//Agricultural Science and Technology Innovation Program, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/ ; Y2022LM09//Central Public-Interest Scientific Institution Basal Research Fund/ ; YYLH05//Nanfan Special Project of Chinese Academy of Agricultural Sciences/ ; 2022YFD1600303//National Key R&amp;D Program of China/ ; }, mesh = {Mice ; Animals ; *Depression/drug therapy/metabolism ; *Polygonum/metabolism ; Brain-Gut Axis ; Phosphatidylinositol 3-Kinases/metabolism ; Antidepressive Agents/pharmacology ; Polysaccharides/pharmacology/metabolism ; Hippocampus ; Stress, Psychological/drug therapy/metabolism ; Disease Models, Animal ; }, abstract = {Polygonum sibiricum polysaccharides (PSP) are one of the main active components of Polygonatum sibiricum, which is a traditional Chinese medicine with food and drug homologies. Recent studies have revealed the antidepressant-like effects of PSP. However, the precise mechanisms have not been clarified. Therefore, the present study was conducted to explore that whether PSP could exert the antidepressant-like effects via microbiota-gut-brain (MGB) axis in chronic unpredictable mild stress (CUMS)-induced depressive mice by transplantation of fecal microbiota (FMT) from PSP administration mice. FMT markedly reversed the depressive-like behaviors of CUMS-induced mice in the open field, the sucrose preference, the tail suspension, the forced swimming, and the novelty-suppressed feeding tests. FMT significantly increased the levels of 5-hydroxytryptamine and norepinephrine, decreased the levels of the pro-inflammatory cytokines in the hippocampus and reduced the levels of corticosterone, an adrenocorticotropic-hormone, in the serum of CUMS-induced mice. In addition, administration of PSP and FMT significantly increased the expressions of ZO-1 and occludin in the colon and decreased the levels of lipopolysaccharide and interferon-γ in the serum of CUMS-induced mice. Moreover, administration of PSP and FMT regulated the signaling pathways of PI3K/AKT/TLR4/NF-κB and ERK/CREB/BDNF. Taken together, these findings indicated that PSP exerted antidepressant-like effects via the MGB axis.}, }
@article {pmid36994745, year = {2023}, author = {Yang, Z and Wang, Q and Liu, Y and Wang, L and Ge, Z and Li, Z and Feng, S and Wu, C}, title = {Gut microbiota and hypertension: association, mechanisms and treatment.}, journal = {Clinical and experimental hypertension (New York, N.Y. : 1993)}, volume = {45}, number = {1}, pages = {2195135}, doi = {10.1080/10641963.2023.2195135}, pmid = {36994745}, issn = {1525-6006}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Hypertension/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; Risk Factors ; *Probiotics/therapeutic use ; }, abstract = {OBJECTIVES: Hypertension is one of the most important risk factors for cardio-cerebral vascular diseases, which brings a heavy economic burden to society and becomes a major public health problem. At present, the pathogenesis of hypertension is unclear. Increasing evidence has proven that the pathogenesis of hypertension is closely related to the dysbiosis of gut microbiota. We briefly reviewed relevant literature on gut microbiota and hypertension to summarize the relationship between gut microbiota and hypertension, linked the antihypertension effects of drugs with their modulation on gut microbiota, and discussed the potential mechanisms of various gut microbes and their active metabolites to alleviate hypertension, thus providing new research ideas for the development of antihypertension drugs.<br><br>METHODS: The relevant literature was collected systematically from scientific database, including Elsevier, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Baidu Scholar, as well as other literature sources, such as classic books of herbal medicine.<br><br>RESULTS: Hypertension can lead to gut microbiota imbalance and gut barrier dysfunction, including increased harmful bacteria and hydrogen sulfide and lipopolysaccharide, decreased beneficial bacteria and short-chain fatty acids, decreased intestinal tight junction proteins and increased intestinal permeability. Gut microbiota imbalance is closely related to the occurrence and development of hypertension. At present, the main methods to regulate the gut microbiota include fecal microbiota transplantation, supplementation of probiotics, antibiotics, diet and exercise, antihypertensive drugs, and natural medicines.<br><br>CONCLUSIONS: Gut microbiota is closely related to hypertension. Investigating the correlation between gut microbiota and hypertension may help to reveal the pathogenesis of hypertension from the perspective of gut microbiota, which is of great significance for the prevention and treatment of hypertension.}, }
@article {pmid36993518, year = {2023}, author = {Hajjar, J and Voigt, A and Conner, M and Swennes, A and Fowler, S and Calarge, C and Mendonca, D and Armstrong, D and Chang, CY and Walter, J and Butte, M and Savidge, T and Oh, J and Kheradmand, F and Petrosino, J}, title = {Common Variable Immunodeficiency Patient Fecal Microbiota Transplant Recapitulates Gut Dysbiosis.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {36993518}, issn = {2693-5015}, support = {P30 CA125123/CA/NCI NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; }, abstract = {PURPOSE: Patients with non-infectious complications have worse clinical outcomes in common variable immunodeficiency (CVID) than those with infections-only. Non-infectious complications are associated with gut microbiome aberrations, but there are no reductionist animal models that emulate CVID. Our aim in this study was to uncover potential microbiome roles in the development of non-infectious complications in CVID.<br><br>METHODS: We examined fecal whole genome shotgun sequencing from patients CVID, and non-infectious complications, infections-only, and their household controls. We also performed Fecal Microbiota transplant from CVID patients to Germ-Free Mice.<br><br>RESULTS: We found potentially pathogenic microbes Streptococcus parasanguinis and Erysipelatoclostridium ramosum were enriched in gut microbiomes of CVID patients with non-infectious complications. In contrast, Fusicatenibacter saccharivorans and Anaerostipes hadrus, known to suppress inflammation and promote healthy metabolism, were enriched in gut microbiomes of infections-only CVID patients. Fecal microbiota transplant from non-infectious complications, infections-only, and their household controls into germ-free mice revealed gut dysbiosis patterns in recipients from CVID patients with non-infectious complications, but not infections-only CVID, or household controls recipients.<br><br>CONCLUSION: Our findings provide a proof of concept that fecal microbiota transplant from CVID patients with non-infectious complications to Germ-Free mice recapitulates microbiome alterations observed in the donors.}, }
@article {pmid36993296, year = {2023}, author = {Chiaro, TR and Bauer, KM and Ost, KS and Stephen-Victor, E and Nelson, MC and Hill, JH and Bell, R and Harwood, M and Voth, W and Jackson, T and Klag, KA and Oâ Connell, RM and Zac Stephens, W and Round, JL}, title = {Clec12a tempers inflammation while restricting expansion of a colitogenic commensal.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.03.16.532997}, pmid = {36993296}, issn = {2692-8205}, support = {T32 AI055434/AI/NIAID NIH HHS/United States ; T32 DK091317/DK/NIDDK NIH HHS/United States ; }, abstract = {Regulation of the microbiota is critical to intestinal health yet the mechanisms employed by innate immunity remain unclear. Here we show that mice deficient in the C-Type-lectin receptor, Clec12a developed severe colitis, which was dependent on the microbiota. Fecal-microbiota-transplantation (FMT) studies into germfree mice revealed a colitogenic microbiota formed within Clec12a [-/-] mice that was marked by expansion of the gram-positive organism, Faecalibaculum rodentium . Treatment with F. rodentium was sufficient to worsen colitis in wild-type mice. Macrophages within the gut express the highest levels of Clec12a. Cytokine and sequencing analysis in Clec12a [-/-] macrophages revealed heighten inflammation but marked reduction in genes associated with phagocytosis. Indeed, Clec12a [-/-] macrophages are impaired in their ability to uptake F. rodentium. Purified Clec12a had higher binding to gram-positive organisms such as F. rodentium . Thus, our data identifies Clec12a as an innate immune surveillance mechanism to control expansion of potentially harmful commensals without overt inflammation.}, }
@article {pmid36990700, year = {2023}, author = {,  and ,  and , }, title = {[Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis (2023)].}, journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases}, volume = {46}, number = {4}, pages = {352-372}, doi = {10.3760/cma.j.cn112147-20221214-00971}, pmid = {36990700}, issn = {1001-0939}, support = {2022-PUMCH-B-107//National High Level Hospital Clinical Research Funding/ ; 2021-I2M-1-003, 2021-I2M-1-056//CAMS Innovation Fund for Medical Sciences/ ; }, mesh = {Adult ; Child ; Child, Preschool ; Humans ; Male ; Adrenal Cortex Hormones/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; *Bronchiectasis/drug therapy ; Bronchodilator Agents/therapeutic use ; Chlorides/therapeutic use ; *Cystic Fibrosis/therapy/drug therapy ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics/therapeutic use ; Deoxyribonucleases/therapeutic use ; Hemoptysis ; Mannitol/therapeutic use ; }, abstract = {Cystic fibrosis (CF) is one of the most common autosomal recessive genetic diseases in Caucasians, but CF patients in China are rare, and it was listed as the first batch of rare diseases in China in 2018. In recent years, CF has been gradually recognized in China, and the number of CF patients reported in China in the past 10 years is more than 2.5 times the total number in the previous 30 years, and the total number of CF patients is estimated to be more than 20 000. The research progress of CF gene modification has led to the innovation of CF treatment. However, the sweat test as an important test for the diagnosis of CF has not been widely implemented in China. At present, the diagnosis and treatment of CF in China still lacks standardized recommendations. In view of these updates, the Chinese Experts Cystic Fibrosis Consensus Committee has formed "the Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis" based on extensive opinion gathering, literatures review, multiple meetings and discussions. This consensus collects 38 core issues related to CF, including pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and patient management. Finally, 32 recommendations were formulated. The consensus used the modified GRADE methodology to grade the evidence evaluation and recommendations. This is the current state of CF consensus in China, and we hope to improve the diagnosis and treatment of CF in China in the future.Summary of recommendationsQuestion 1: How can CF be identified?CF should be suspected if there is: (1) a family history of CF; (2) delayed meconium expulsion or meconium ileus; (3) pancreatic exocrine insufficiency, mainly characterized by long-standing steatorrhea and malnutrition; (4) recurrent lower respiratory tract infections of infantile onset, especially Pseudomonas aeruginosa (PA), Staphylococcus aureus infections of respiratory aetiology; (5) chronic sinusitis, especially when combined with juvenile presentation of nasal polyps; (6) chest CT abnormalities such as the presence of air trapping, bronchiectasis (upper lobe predominant); (7) pseudo-Bartter syndrome; (8) absence of vas deferens in males; (9) clubbing in young bronchiectasis patients(1C).Question 2: What are the diagnostic criteria for CF?1.1 Presence of one or more of the characteristic clinical manifestations or family history consistent with CF, and meeting at least one of the following definite diagnostic criteria in 1.2 or 1.3.1.2 Sweat chloride testing:(1) Concentrations of more than 60 mmol/L are diagnostic; (2) concentrations between 30-59 mmol/L are intermediate, and genetic variation must be considered to confirm the diagnosis; (3) concentrations less than 30 mmol/L are considered normal.1.3 Genetic testing:(1) Detection of two disease-causing CFTR(cystic fibrosis transmembrane conductance regulator) mutations on biallelic alleles; (2) The CFTR variants are of undetermined significance, but tests such as sweat chloride concentration, intestinal current measurement, or nasal mucosal potential difference suggest abnormal CFTR function, then CF is diagnostic(1C).Question 3: What is the diagnostic process for CF arranged?Sweat chloride testing and CFTR gene analysis are recommended in all patients suspected of CF(1D).Question 4: What is the value of sweat chloride testing in the diagnosis of CF?Sweat chloride testing is the gold standard for the clinical diagnosis of CF(1C).Question 5: What is the value of CFTR genetic testing in Chinese CF diagnosis?Biallelic pathogenic variants of CFTR are a definitive diagnosis of CF(1D).Question 6: What is the diagnostic value of imaging for CF?Chest CT is a sensitive test for early stages of lung disease in patients with CF and is appropriate in younger patients and to assess disease progression. The imaging findings of abdominal visceral involvement in CF lack specificity(2C).Question 7: How to evaluate the pancreatic function of CF patients?Fecal elastase may be used as the first indicator to assess pancreatic exocrine function in patients with CF (2C).Question 8: How to diagnose hepatic abnormality of CF?CF related liver disease was diagnosed when CF was confirmed and 2 of the following 4 criteria were met: (1) hepatomegaly and/or splenomegaly confirmed by ultrasound; (2) ALT, AST, and GGT on three consecutive occasions above the upper limit of normal on three consecutive occasions for more than 12 months and excluding other causes; (3) had evidence of liver involvement, portal hypertension, or bile duct dilatation by ultrasound; (4) liver biopsy confirmation (focal biliary cirrhosis or multilobular cirrhosis) may be indicated if the diagnosis is suspected(2D).Question 9: How to identify pulmonary exacerbations in patients with CF?Pulmonary exacerbations are indicated when any 4 of the following 12 signs or symptoms are met: increased sputum; new onset haemoptysis or increased haemoptysis; exacerbation of cough; increased dyspnea; malaise, fatigue, or somnolence; body temperature above 38 ℃; anorexia or weight loss; sinus pain or tenderness; increased sinus secretions; new chest signs; FEV1≥10% decline from previous; imaging changes suggestive of pulmonary infection(2D).Question 10: How to diagnose CF related diabetes?Diagnostic criteria for CF related diabetes are the same as those for diabetes in the population(1D).Question 11: How to evaluate the nutritional status of CF patients?Anthropometric parameters reflecting nutritional status should be assessed regularly. And the goal of nutritional assessment is to evaluate and monitor whether pediatric patients are achieving normal standards of growth and development or whether adult patients are maintaining adequate nutritional status(1C).Question 12: Does CF require pathological examination as a diagnostic basis?Pathohistological biopsy is not recommended as a first-line diagnostic method in patients with a suspected diagnosis of CF(1D).Question 13: Do CF patients need long-term macrolides?At least 6 months of azithromycin treatment is recommended for CF patients with chronic PA infection(2A).Question 14: Do CF patients need long-term inhalation of hypertonic saline?Long term treatment with hypertonic saline is recommended for patients with CF(1A).Question 15: Do CF patients need long-term inhalation of Dornase alfa(DNase)?Long term use of DNase is recommended in patients with CF aged 6 years and older(1A).Question 16: Do CF patients need inhalation of mannitol?Inhaled mannitol therapy is recommended for more than 6 months in patients with CF aged 18 years and older when other inhaled treatments are unavailable or intolerable(2A).Question 17: How to deal with PA found in the sputum culture of CF patients?When sputum cultures from patients with CF are positive for PA, it needs to determine the characteristics of the infection first. The purpose for acute infection is to eradicate PA. Chronic colonization does not need to be eradicated, and the main purpose is to reduce the bacterial load and improve symptoms(1A).Question 18: Do CF patients need inhalation of antibiotics?Inhaled antibiotic therapy is recommended for CF patients with PA infection(1A).Question 19: Do CF patients need inhaled or systemic corticosteroids?In patients with CF without asthma or ABPA, routine inhaled or systemic glucocorticoids are not recommended (2A).Question 20: Do CF patients need to inhale bronchodilators?Bronchodilators can be used in the short term to improve symptoms in patients with CF in the presence of airway obstruction, but the long-term benefit is insufficient (2B).Question 21: Do CF patients need expectorant medicine?Patients with CF can take acetylcysteine orally or aerosolized(2A).Question 22: How to deal with acute pulmonary exacerbation in CF patients?Intensive implementation of non-antimicrobial therapy is recommended during pulmonary exacerbations in patients with CF. Antimicrobials with activity against PA were selected for empirical treatment, and the treatment was adjusted according to the results of bacterial culture and drug susceptibility testing. A 21-day long course of anti-infective therapy is not recommended(1B).Question 23: How to treat CF patients with ABPA?Medical therapy is recommended for CF patients with ABPA who meet any of the following criteria: patients with elevated immunoglobulin E levels and concomitant worsening of pulmonary function and/or pulmonary symptoms, or imaging suggesting new infiltrative foci in the chest(1D).Glucocorticoids are recommended for ABPA exacerbations in CF patients without contraindications(2D).Itraconazole should be added if the patient presents with poor response to corticosteroids, recurrence of ABPA, corticosteroid dependence, or corticosteroid toxicity(2D).Question 24: Is lung transplantation recommended for patients with CF? When is it recommended?Patients with CF may be evaluated for lung transplantation when they meet the following criteria after optimal medical therapy: (1) FEV1<30% predicted; (2) FEV1<40% predicted (<50% predicted in children) with the following: 6-minute walk distance<400 meters; PaCO2>50 mmHg(1 mmHg=0.133 kPa); hypoxia at rest or after activity; pulmonary artery pressure measured by cardiotocography>50 mmHg or right heart dysfunction; continued deterioration despite aggressive supplementation of nutritional support; two exacerbations requiring intravenous antibiotic therapy per year; massive hemoptysis (>240 ml) requiring pulmonary artery embolization; presented with pneumothorax; (3) FEV1<50% predicted and rapid decline in lung function or rapid worsening of symptoms; (4) Presented with an acute exacerbation requiring positive pressure mechanical ventilation(2C).Question 25: How to deal with pancreatic disease in CF patients?Pancreatic enzyme replacement therapy is recommended in patients with CF pancreatic disease(1A).Question 26: How to deal with hepatobiliary disease in CF patients?Ursodeoxycholic acid is not recommended in asymptomatic patients with CF hepatobiliary disease(2B).Question 27: How to deal with gastrointestinal problems such as acid regurgitation in CF patients?Acid suppression is recommended for CF patients with gastrointestinal symptoms such as acid regurgitation (2B).Question 28: How to deal with CF related diabetes?Insulin therapy is recommended in CF related diabetes(1B).Question 29: How should nutritional support be given to patients with CF?Energy intake in patients with CF is recommended to be 110%-200% of the energy requirement of a healthy person under equivalent physiological conditions. And maintaining adequate protein, appropriate intake of fats, electrolytes, and fat-soluble vitamins are recommanded(1A).Question 30: How should respiratory rehabilitation be performed in patients with CF?Airway clearance therapy and appropriate exercise are recommended for patients with CF(1A).Question 31: What is included in the follow-up of CF patient?Patients with CF should have regular follow-up. Adult patients are recommended to be followed every 3-6 months, and children should be followed more frequently(2A).Question 32: How should CF patients avoid infections?Inpatients and outpatients are recommended to be separated according to microbiota carriage status(1D).Good hand hygiene is recommended for the patients with CF and their contacts(1D).It is recommended that CF patients wear masks in healthcare settings. This may reduce the release of potentially infectious aerosols during coughing (1D).Annual influenza vaccination is recommended for patients with CF>6 months of age and for all family members of patients with CF and all healthcare workers caring for these patients(2D).Palivizumab may be considered for the prevention of respiratory syncytial virus infection in patients with CF under two years of age(2A).}, }
@article {pmid36990372, year = {2023}, author = {Guzzardi, MA and La Rosa, F and Iozzo, P}, title = {Trust the gut: Outcomes of gut microbiota transplant in metabolic and cognitive disorders.}, journal = {Neuroscience and biobehavioral reviews}, volume = {149}, number = {}, pages = {105143}, doi = {10.1016/j.neubiorev.2023.105143}, pmid = {36990372}, issn = {1873-7528}, mesh = {Child ; Humans ; *Metabolic Syndrome/therapy ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/therapy ; Trust ; Obesity/therapy ; *Cognitive Dysfunction/therapy ; }, abstract = {Type 2 diabetes mellitus (T2DM) is a main public health concern, with increasing prevalence and growingly premature onset in children, in spite of emerging and successful therapeutic options. T2DM promotes brain aging, and younger age at onset is associated with a higher risk of subsequent dementia. Preventive strategies should address predisposing conditions, like obesity and metabolic syndrome, and be started from very early and even prenatal life. Gut microbiota is an emerging target in obesity, diabetes and neurocognitive diseases, which could be safely modulated since pregnancy and infancy. Many correlative studies have supported its involvement in disease pathophysiology. Faecal material transplantation (FMT) studies have been conducted in clinical and preclinical settings to deliver cause-effect proof and mechanistic insights. This review provides a comprehensive overview of studies in which FMT was used to cure or cause obesity, metabolic syndrome, T2DM, cognitive decline and Alzheimer's disease, including the evidence available in early life. Findings were analysed to dissect consolidated from controversial results, highlighting gaps and possible future directions.}, }
@article {pmid36990294, year = {2023}, author = {Kralicek, SE and Jenkins, C and Allegretti, JR and Lewis, JD and Osman, M and Hecht, GA}, title = {Transmission of the Potential Pathogen Atypical Enteropathogenic Escherichia coli by Fecal Microbiota Transplant.}, journal = {Gastroenterology}, volume = {165}, number = {1}, pages = {279-282.e1}, pmid = {36990294}, issn = {1528-0012}, support = {R21 AI142515/AI/NIAID NIH HHS/United States ; R24 AI118629/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Enteropathogenic Escherichia coli ; Fecal Microbiota Transplantation ; *Escherichia coli Infections/therapy ; Diarrhea ; }, }
@article {pmid36990029, year = {2023}, author = {Hao, H and Li, Z and Qiao, SY and Qi, Y and Xu, XY and Si, JY and Liu, YH and Chang, L and Shi, YF and Xu, B and Wei, ZH and Kang, LN}, title = {Empagliflozin ameliorates atherosclerosis via regulating the intestinal flora.}, journal = {Atherosclerosis}, volume = {371}, number = {}, pages = {32-40}, doi = {10.1016/j.atherosclerosis.2023.03.011}, pmid = {36990029}, issn = {1879-1484}, mesh = {Male ; Mice ; Animals ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation/methods ; *Atherosclerosis/prevention &amp; control ; Apolipoproteins E ; }, abstract = {BACKGROUND AND AIMS: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) has been reported to attenuate atherosclerosis. Further, it has been suggested that intestinal flora influences atherosclerosis progression. Herein we aimed to investigate whether SGLT2i can alleviate atherosclerosis through intestinal flora.<br><br>METHODS: Six-week-old male ApoE[-/-] mice fed a high-fat diet were gavaged either empagliflozin (SGLT2i group, n&#xa0;=&#xa0;9) or saline (Ctrl group, n&#xa0;=&#xa0;6) for 12 weeks. Feces were collected from both groups at the end of the experiment for fecal microbiota transplantation (FMT). Another 12 six-week-old male ApoE[-/-] mice were fed a high-fat diet and received FMT with feces either from SGLT2i (FMT-SGLT2i group, n&#xa0;=&#xa0;6) or from Ctrl (FMT-Ctrl group, n&#xa0;=&#xa0;6) groups. Blood, tissue, and fecal samples were collected for subsequent analyses.<br><br>RESULTS: In comparison with Ctrl group, atherosclerosis was less severe in the SGLT2i group (p&#xa0;<&#xa0;0.0001), and the richness of probiotic, such as f_Coriobacteriaceae, f_S24-7, f_Lachnospiraceae, and f_Adlercreutzia, was higher in feces. Besides, empagliflozin resulted in a significant reduction in the inflammatory response and altered intestinal flora metabolism. Interestingly, compared with FMT-Ctrl, FMT-SGLT2i also showed a reduction in atherosclerosis and systemic inflammatory response, as well as changes in the component of intestinal flora and pertinent metabolites similar to SGLT2i group.<br><br>CONCLUSIONS: Empagliflozin seems to mitigate atherosclerosis partly by regulating intestinal microbiota, and this anti-atherosclerotic effect can be transferred through intestinal flora transplantation.}, }
@article {pmid36988432, year = {2023}, author = {Chen, LA and Oliva-Hemker, M and Radin, A and Weidner, M and O'Laughlin, BD and Sears, CL and Javitt, NB and Hourigan, SK}, title = {Longitudinal Bile Acid Composition Changes Following Faecal Microbiota Transplantation for Clostridioides difficile Infection in Children With and Without Underlying Inflammatory Bowel Disease.}, journal = {Journal of Crohn's &amp; colitis}, volume = {17}, number = {8}, pages = {1364-1368}, pmid = {36988432}, issn = {1876-4479}, support = {K23 DK119544/DK/NIDDK NIH HHS/United States ; K23DK119544/DK/NIDDK NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Humans ; Child ; Fecal Microbiota Transplantation/methods ; Bile Acids and Salts ; *Clostridioides difficile ; Recurrence ; *Clostridium Infections/therapy/microbiology ; *Inflammatory Bowel Diseases/complications ; Bacteria ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Faecal microbiota transplant [FMT] is effective in treating recurrent Clostridioides difficile infection [CDI] and restores gut microbiota composition. This is unlikely to account for its entire mechanism of efficacy, as studies have shown that factors such as bile acids influence the risk of infection by affecting Clostridioides difficile germination. We therefore aimed to investigate longitudinal changes in the gut bile acid composition after FMT performed for recurrent CDI, in children with and without inflammatory bowel disease [IBD].<br><br>METHODS: Eight children received FMT; five had underlying IBD. Primary and secondary faecal bile acids were measured by liquid chromatography-mass spectrometry in recipients [pre-FMT and longitudinally post-FMT for up to 6 months] and donors.<br><br>RESULTS: Pre-FMT, recipients had higher primary and lower secondary bile acid proportions compared with donors. Post-FMT, there was a gradual increase of secondary and decrease of primary bile acids. Whereas gut bacterial diversity had been shown to be restored in all children shortly after FMT, normalisation of bile acids to donor levels occurred only by 6 months. In children with IBD, although microbiota diversity returned to pre-FMT levels within 6 months, secondary bile acids remained at donor levels.<br><br>CONCLUSIONS: The differences in bile acid profiles compared with gut bacterial diversity post-FMT suggests that interactions between the two may be more complex than previously appreciated and may contribute to FMT efficacy in different ways. This initial finding demonstrates the need to further investigate gut metabolites in larger cohorts, with longitudinal sampling to understand the mechanisms of FMT effectiveness.}, }
@article {pmid36986068, year = {2023}, author = {Rodriguez, DM and Hintze, KJ and Rompato, G and Stewart, EC and Barton, AH and Mortensen-Curtis, E and Green, PA and Van Wettere, AJ and Thomas, AJ and Benninghoff, AD}, title = {Basal Diet Fed to Recipient Mice Was the Driving Factor for Colitis and Colon Tumorigenesis, despite Fecal Microbiota Transfer from Mice with Severe or Mild Disease.}, journal = {Nutrients}, volume = {15}, number = {6}, pages = {}, pmid = {36986068}, issn = {2072-6643}, support = {USDA-2018-67017-27516//United States Department of Agriculture/ ; UTA-01178//Utah Agricultural Experiment Station/ ; UTA-01456//Utah Agricultural Experiment Station/ ; }, mesh = {Mice ; Animals ; *Fecal Microbiota Transplantation ; *Colitis ; Carcinogenesis ; Cell Transformation, Neoplastic ; Inflammation ; Diet, Western ; Mice, Inbred C57BL ; }, abstract = {Consumption of the total Western diet (TWD) in mice has been shown to increase gut inflammation, promote colon tumorigenesis, and alter fecal microbiome composition when compared to mice fed a healthy diet, i.e., AIN93G (AIN). However, it is unclear whether the gut microbiome contributes directly to colitis-associated CRC in this model. The objective of this study was to determine whether dynamic fecal microbiota transfer (FMT) from donor mice fed either the AIN basal diet or the TWD would alter colitis symptoms or colitis-associated CRC in recipient mice, which were fed either the AIN diet or the TWD, using a 2 × 2 factorial experiment design. Time-matched FMT from the donor mice fed the TWD did not significantly enhance symptoms of colitis, colon epithelial inflammation, mucosal injury, or colon tumor burden in the recipient mice fed the AIN diet. Conversely, FMT from the AIN-fed donors did not impart a protective effect on the recipient mice fed the TWD. Likewise, the composition of fecal microbiomes of the recipient mice was also affected to a much greater extent by the diet they consumed than by the source of FMT. In summary, FMT from the donor mice fed either basal diet with differing colitis or tumor outcomes did not shift colitis symptoms or colon tumorigenesis in the recipient mice, regardless of the basal diet they consumed. These observations suggest that the gut microbiome may not contribute directly to the development of disease in this animal model.}, }
@article {pmid36985379, year = {2023}, author = {Dossaji, Z and Khattak, A and Tun, KM and Hsu, M and Batra, K and Hong, AS}, title = {Efficacy of Fecal Microbiota Transplant on Behavioral and Gastrointestinal Symptoms in Pediatric Autism: A Systematic Review.}, journal = {Microorganisms}, volume = {11}, number = {3}, pages = {}, pmid = {36985379}, issn = {2076-2607}, abstract = {Background and Aims: There is a high prevalence of gastrointestinal-related (GI) symptoms among children with autism spectrum disorder (ASD), which is associated with the severity of behavioral symptoms. Fecal microbiota transplantation (FMT) is a proposed therapeutic strategy that aims to address the dysregulation of the gut microbiome among children with ASD. Our study performed the first systematic review aimed to evaluate the benefits of FMT on the behavioral and gastrointestinal symptoms of pediatric patients with autism. Methods: A literature search was performed using variations of the keywords "pediatrics" and "fecal microbiota transplantation" in PubMed, EMBASE, CINAHL, Cochrane, and Web of Science from inception to 30 June 2022. Four studies that met the eligibility criteria were included in the systematic review. The efficacy of FMT on behavioral symptoms was measured by the difference in Aberrant Behavior Checklist (ABC) and Child Autism Rating Scale (CARS) scores before and after FMT. Results: We found a statistically significant improvement (p < 0.05) in ABC and CARS scores following FMT, with a statistically significant decrease in scores observed across all studies. In addition, substantial improvements in gastrointestinal symptoms were observed across all studies. Conclusion: Our findings suggest that FMT may offer a promising intervention for treating both behavioral and gastrointestinal symptoms in pediatric patients with autism.}, }
@article {pmid36983718, year = {2023}, author = {Zhang, Z and Chen, H and Huang, J and Zhang, S and Li, Z and Kong, C and Mao, Y and Han, B}, title = {Early Administration of Vancomycin Inhibits Pulmonary Embolism by Remodeling Gut Microbiota.}, journal = {Journal of personalized medicine}, volume = {13}, number = {3}, pages = {}, pmid = {36983718}, issn = {2075-4426}, support = {81872245; 8180360//National Natural Science Foundation of China/ ; 2022MHBJ01//Minhang Hospital/ ; 2022YQ052//Shanghai Municipal Health Commission/ ; SKLGE-2112; 20214Y0327//Shanghai/ ; }, abstract = {Pulmonary embolism (PE) is a common and potentially fatal condition in the emergency department, and early identification of modifiable risk factors for prevention and management is highly desirable. Although gut dysbiosis is associated with a high incidence of venous thromboembolism, the role and mechanisms of the gut microbiome in the pathogenesis of venous thromboembolism, especially PE, remain unexplored. Here, we attempted to elucidate the benefits of the gut microbiome in the pathogenesis of PE using multiple antibiotics and fecal microbiota transplantation (FMT) for early intervention in a classical mouse model of PE. The results showed that early administration of various antibiotics (except ampicillin) could inhibit pulmonary thrombosis to a certain extent and reduced mortality in young and old mice with PE. Among them, vancomycin has the best inhibitory effect on PE. With the help of gut microbiota sequencing analysis, we found that antibiotic treatment can reshape the gut microbiota; especially vancomycin can significantly improve the gut microbiota structure in PE mice. Furthermore, FMT could transfer vancomycin-modified gut microbes into mice and inhibit the pathogenesis of PE, possibly due to increased intestinal colonization by Parasutterella. These data elucidate the underlying molecular mechanism by which early administration of vancomycin can remodel the gut microbiota to suppress PE, providing new clues for clinical optimization and development of PE prevention strategies.}, }
@article {pmid36983199, year = {2023}, author = {Palumbo, VD and Tutino, R and Messina, M and Santarelli, M and Nigro, C and Lo Secco, G and Piceni, C and Montanari, E and Barletta, G and Venturelli, P and Geraci, G and Bonventre, S and Lo Monte, AI}, title = {Altered Gut Microbic Flora and Haemorrhoids: Could They Have a Possible Relationship?.}, journal = {Journal of clinical medicine}, volume = {12}, number = {6}, pages = {}, pmid = {36983199}, issn = {2077-0383}, abstract = {To date, the exact pathophysiology of haemorrhoids is poorly understood. The different philosophies on haemorrhoids aetiology may lead to different approaches of treatment. A pathogenic theory involving a correlation between altered anal canal microflora, local inflammation, and muscular dyssynergia is proposed through an extensive review of the literature. Since the middle of the twentieth century, three main theories exist: (1) the varicose vein theory, (2) the vascular hyperplasia theory, and (3) the concept of a sliding anal lining. These phenomena determine changes in the connective tissue (linked to inflammation), including loss of organization, muscular hypertrophy, fragmentation of the anal subepithelial muscle and the elastin component, and vascular changes, including abnormal venous dilatation and vascular thrombosis. Recent studies have reported a possible involvement of gut microbiota in gut motility alteration. Furthermore, dysbiosis seems to represent the leading cause of bowel mucosa inflammation in any intestinal district. The alteration of the gut microbioma in the anorectal district could be responsible for haemorrhoids and other anorectal disorders. A deeper knowledge of the gut microbiota in anorectal disorders lays the basis for unveiling the roles of these various gut microbiota components in anorectal disorder pathogenesis and being conductive to instructing future therapeutics. The therapeutic strategy of antibiotics, prebiotics, probiotics, and fecal microbiota transplantation will benefit the effective application of precision microbiome manipulation in anorectal disorders.}, }
@article {pmid36980767, year = {2023}, author = {Mareschal, J and Hemmer, A and Douissard, J and Dupertuis, YM and Collet, TH and Koessler, T and Toso, C and Ris, F and Genton, L}, title = {Surgical Prehabilitation in Patients with Gastrointestinal Cancers: Impact of Unimodal and Multimodal Programs on Postoperative Outcomes and Prospects for New Therapeutic Strategies-A Systematic Review.}, journal = {Cancers}, volume = {15}, number = {6}, pages = {}, pmid = {36980767}, issn = {2072-6694}, abstract = {The advantages of prehabilitation in surgical oncology are unclear. This systematic review aims to (1) evaluate the latest evidence of preoperative prehabilitation interventions on postoperative outcomes after gastrointestinal (GI) cancer surgery and (2) discuss new potential therapeutic targets as part of prehabilitation. Randomized controlled trials published between January 2017 and August 2022 were identified through Medline. The population of interest was oncological patients undergoing GI surgery. Trials were considered if they evaluated prehabilitation interventions (nutrition, physical activity, probiotics and symbiotics, fecal microbiota transplantation, and ghrelin receptor agonists), alone or combined, on postoperative outcomes. Out of 1180 records initially identified, 15 studies were retained. Evidence for the benefits of unimodal interventions was limited. Preoperative multimodal programs, including nutrition and physical activity with or without psychological support, showed improvement in postoperative physical performance, muscle strength, and quality of life in patients with esophagogastric and colorectal cancers. However, there was no benefit for postoperative complications, hospital length of stay, hospital readmissions, and mortality. No trial evaluated the impact of fecal microbiota transplantation or oral ghrelin receptor agonists. Further studies are needed to confirm our findings, identify patients who are more likely to benefit from surgical prehabilitation, and harmonize interventions.}, }
@article {pmid36979685, year = {2023}, author = {Piccioni, A and Rosa, F and Mannucci, S and Manca, F and Merra, G and Chiloiro, S and Candelli, M and Covino, M and Gasbarrini, A and Franceschi, F}, title = {Gut Microbiota, LADA, and Type 1 Diabetes Mellitus: An Evolving Relationship.}, journal = {Biomedicines}, volume = {11}, number = {3}, pages = {}, pmid = {36979685}, issn = {2227-9059}, abstract = {There is much evidence confirming the crucial role played by the gut microbiota in modulating the immune system in the onset of autoimmune diseases. In this article, we focus on the relationship between alterations in the microbiome and the onset of diabetes mellitus type 1 and LADA, in light of the latest evidence. We will then look at both how the role of the gut microbiota appears to be increasingly crucial in the pathogenesis of these disorders and how this aspect may be instrumental in the development of new potential therapeutic strategies that modulate the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation.}, }
@article {pmid36977964, year = {2023}, author = {Balzano, T}, title = {Active Clinical Trials in Hepatic Encephalopathy: Something Old, Something New and Something Borrowed.}, journal = {Neurochemical research}, volume = {48}, number = {8}, pages = {2309-2319}, pmid = {36977964}, issn = {1573-6903}, support = {JUAN DE LA CIERVA-INCORPORACI&#xd3;N (IJC2020-043918-I)//MCIN/AEI /10.13039/501100011033 and European Union NextGenerationEU/PRTR/ ; }, mesh = {Animals ; Horses ; *Hepatic Encephalopathy/drug therapy ; Rifaximin/therapeutic use ; Lactulose/therapeutic use ; Quality of Life ; *Anti-Infective Agents/therapeutic use ; }, abstract = {Hepatic encephalopathy (HE) is a potentially reversible neurocognitive syndrome that occurs in patients with acute or chronic liver disease. Currently, most of the therapies for HE aim to reduce ammonia production or increase its elimination. To date, only two agents have been approved as treatments for HE: lactulose and rifaximin. Many other drugs have also been used, but data to support their use are limited, preliminary or lacking. The aim of this review is to provide an overview and discussion of the current development of treatments for HE. Data from ongoing clinical trials in HE were obtained from the ClinicalTrials.gov website, and a breakdown analysis of studies that were active on August 19th, 2022, was performed. Seventeen registered and ongoing clinical trials for therapeutics targeting HE were identified. More than 75% of these agents are in phase II (41.2%) or in phase III (34.7%). Among them, there are many old acquaintances in the field, such as lactulose and rifaximin, some new entries such as fecal microbiota transplantation and equine anti-thymocyte globulin, an immunosuppressive agent, but also some therapies borrowed from other conditions, such as rifamycin SV MMX and nitazoxanide, two antimicrobial agents FDA approved for the treatment of some types of diarrheas or VE303 and RBX7455, two microbiome restoration therapies, currently used as treatment of high-risk Clostridioides difficile infections. If working, some of these drugs could soon be used as valid alternatives to current therapies when ineffective or be approved as novel therapeutic approaches to improve the quality of life of HE patients.}, }
@article {pmid36977440, year = {2023}, author = {Dang, Z and Gao, M and Wang, L and Wu, J and Guo, Y and Zhu, Z and Huang, H and Kang, G}, title = {Synthetic bacterial therapies for intestinal diseases based on quorum-sensing circuits.}, journal = {Biotechnology advances}, volume = {65}, number = {}, pages = {108142}, doi = {10.1016/j.biotechadv.2023.108142}, pmid = {36977440}, issn = {1873-1899}, mesh = {Humans ; Quorum Sensing/genetics ; Bacteria ; *Gastrointestinal Microbiome/genetics ; Gene Regulatory Networks ; *Intestinal Diseases ; }, abstract = {Bacterial therapy has become a key strategy against intestinal infectious diseases in recent years. Moreover, regulating the gut microbiota through traditional fecal microbiota transplantation and supplementation of probiotics faces controllability, efficacy, and safety challenges. The infiltration and emergence of synthetic biology and microbiome provide an operational and safe treatment platform for live bacterial biotherapies. Synthetic bacterial therapy can artificially manipulate bacteria to produce and deliver therapeutic drug molecules. This method has the advantages of solid controllability, low toxicity, strong therapeutic effects, and easy operation. As an essential tool for dynamic regulation in synthetic biology, quorum sensing (QS) has been widely used for designing complex genetic circuits to control the behavior of bacterial populations and achieve predefined goals. Therefore, QS-based synthetic bacterial therapy might become a new direction for the treatment of diseases. The pre-programmed QS genetic circuit can achieve a controllable production of therapeutic drugs on particular ecological niches by sensing specific signals released from the digestive system in pathological conditions, thereby realizing the integration of diagnosis and treatment. Based on this as well as the modular idea of synthetic biology, QS-based synthetic bacterial therapies are divided into an environmental signal sensing module (senses gut disease physiological signals), a therapeutic molecule producing module (plays a therapeutic role against diseases), and a population behavior regulating module (QS system). This review article summarized the structure and function of these three modules and discussed the rational design of QS gene circuits as a novel intervention strategy for intestinal diseases. Moreover, the application prospects of QS-based synthetic bacterial therapy were summarized. Finally, the challenges faced by these methods were analyzed to make the targeted recommendations for developing a successful therapeutic strategy for intestinal diseases.}, }
@article {pmid36975808, year = {2023}, author = {Madden, GR and Rigo, I and Boone, R and Abhyankar, MM and Young, MK and Basener, W and Petri, WA}, title = {Novel Biomarkers, Including tcdB PCR Cycle Threshold, for Predicting Recurrent Clostridioides difficile Infection.}, journal = {Infection and immunity}, volume = {91}, number = {4}, pages = {e0009223}, pmid = {36975808}, issn = {1098-5522}, support = {R01 AI152477/AI/NIAID NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; R01 AI124214/AI/NIAID NIH HHS/United States ; T32 AI055432/AI/NIAID NIH HHS/United States ; KL2 TR003016/TR/NCATS NIH HHS/United States ; K23 AI163368/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Clostridioides difficile/genetics ; *Bacterial Toxins/genetics ; Interleukin-8 ; Interleukin-6 ; Bayes Theorem ; Endothelial Growth Factors/therapeutic use ; Epidermal Growth Factor/therapeutic use ; *Clostridium Infections/diagnosis/drug therapy ; Biomarkers/analysis ; Polymerase Chain Reaction ; }, abstract = {Traditional clinical models for predicting recurrent Clostridioides difficile infection do not perform well, likely owing to the complex host-pathogen interactions involved. Accurate risk stratification using novel biomarkers could help prevent recurrence by improving underutilization of effective therapies (i.e., fecal transplant, fidaxomicin, bezlotoxumab). We used a biorepository of 257 hospitalized patients with 24 features collected at diagnosis, including 17 plasma cytokines, total/neutralizing anti-toxin B IgG, stool toxins, and PCR cycle threshold (CT) (a proxy for stool organism burden). The best set of predictors for recurrent infection was selected by Bayesian model averaging for inclusion in a final Bayesian logistic regression model. We then used a large PCR-only data set to confirm the finding that PCR CT predicts recurrence-free survival using Cox proportional hazards regression. The top model-averaged features were (probabilities of >0.05, greatest to least): interleukin 6 (IL-6), PCR CT, endothelial growth factor, IL-8, eotaxin, IL-10, hepatocyte growth factor, and IL-4. The accuracy of the final model was 0.88. Among 1,660 cases with PCR-only data, cycle threshold was significantly associated with recurrence-free survival (hazard ratio, 0.95; P < 0.005). Certain biomarkers associated with C. difficile infection severity were especially important for predicting recurrence; PCR CT and markers of type 2 immunity (endothelial growth factor [EGF], eotaxin) emerged as positive predictors of recurrence, while type 17 immune markers (IL-6, IL-8) were negative predictors. In addition to novel serum biomarkers (particularly, IL-6, EGF, and IL-8), the readily available PCR CT may be critical to augment underperforming clinical models for C. difficile recurrence.}, }
@article {pmid36970196, year = {2023}, author = {Fan, X and Mai, C and Zuo, L and Huang, J and Xie, C and Jiang, Z and Li, R and Yao, X and Fan, X and Wu, Q and Yan, P and Liu, L and Chen, J and Xie, Y and Leung, EL}, title = {Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice.}, journal = {Acta pharmaceutica Sinica. B}, volume = {13}, number = {3}, pages = {1164-1179}, pmid = {36970196}, issn = {2211-3835}, abstract = {Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10[+] M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10[+] M2 macrophage production.}, }
@article {pmid36969340, year = {2023}, author = {Tian, H and Wang, J and Feng, R and Zhang, R and Liu, H and Qin, C and Meng, L and Chen, Y and Fu, Y and Liang, D and Yuan, X and Zhai, Y and Zhu, Q and Jin, L and Teng, J and Ding, X and Wang, X}, title = {Efficacy of faecal microbiota transplantation in patients with progressive supranuclear palsy-Richardson's syndrome: a phase 2, single centre, randomised clinical trial.}, journal = {EClinicalMedicine}, volume = {58}, number = {}, pages = {101888}, pmid = {36969340}, issn = {2589-5370}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has demonstrated efficacy in treating gastrointestinal (GI) diseases, such as Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). GI dysfunction is a frequent and occasionally dominating symptom of progressive supranuclear palsy-Richardson's syndrome (PSP-RS). However, it is not known whether FMT has clinical efficacy for PSP-RS.<br><br>METHODS: This 36-week, randomised, placebo-controlled, parallel-group, phase 2 clinical trial was performed at a university tertiary referral hospital in China. From August 15 2021 to December 31 2021, a total of 68 newly diagnosed patients with PSP-RS (male 40 [59%], female 28 [41%]) who had never received any antiparkinsonian medications were enrolled and randomly assigned to receive either healthy donor FMT (n&#xa0;=&#xa0;34, FMT group) or a mixture of 0.9% saline and food colouring (E150c) as sham transplantation (n&#xa0;=&#xa0;34, placebo group) through transendoscopic enteral tubing (TET). Two days after oral antibiotics, participants received 1 week of transplantation. After an interval of 4 weeks, retransplantation was performed. Then, the last transplantation was given after another interval of 4 weeks, and the participants were followed up for 24 weeks (week 36). Clinicaltrials.gov identifier: ChiCTR-2100045397.<br><br>FINDINGS: Among 68 patients who were randomised (mean age, 67.2 (SD 5.1); 40 [59%] were male, 28 [41%] were female), 63 participants completed the trial. Efficacy analyses were performed on the intention-to-treat (ITT) analysis set. At week 16, the mean PSP Rating Scale (PSPRS) scores (the primary outcome) improved from 40.1 (SD 7.6) to 36.9 (SD 5.9) in the FMT group, whereas the scores changed from 40.1 (SD 6.9) to 41.7 (SD 6.2) in the placebo group, for a treatment benefit of 4.3 (95% CI, 3.2-5.4) (P&#xa0;<&#xa0;0.0001). After 3-cycle intervention, symptoms of constipation, depression, and anxiety (the secondary outcome) improved significantly at week 16 in the FMT group compared with the placebo group, the majority of which were maintained at the 24-week follow-up (week 36).<br><br>INTERPRETATION: Our findings suggest that, compared with placebo, FMT treatment significantly improved motor and nonmotor symptoms in patients with PSP-RS, as well as reduced intestinal inflammation and enhanced the intestinal barrier by regulating the intestinal microbiota composition.<br><br>FUNDING: The National Natural Science Foundation of China (No. 82122022, 82171248, 81873791, and 82230084), Natural Science Foundation of Henan Province for Excellent Young Scholars (no. 202300410357), and Henan Province Young and Middle-Aged Health Science and Technology Innovation Talent Project (YXKC2020033).}, }
@article {pmid36968968, year = {2023}, author = {Garey, KW and Feuerstadt, P and Dubberke, ER and Guo, A and Tillotson, GS}, title = {Effect of fecal microbial transplantation on Clostridioides difficile infection: dysbiosis, metabolites and health related quality of life.}, journal = {Open forum infectious diseases}, volume = {10}, number = {3}, pages = {ofad113}, doi = {10.1093/ofid/ofad113}, pmid = {36968968}, issn = {2328-8957}, }
@article {pmid36968571, year = {2023}, author = {Tucker, EC and Haylock-Jacobs, S and Rapaic, M and Dann, LM and Bryant, RV and Costello, SP}, title = {Stool donor screening within a Therapeutic Goods Administration compliant donor screening program for fecal microbiota transplantation.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {7}, number = {3}, pages = {172-177}, pmid = {36968571}, issn = {2397-9070}, abstract = {BACKGROUND AND AIM: This study evaluates whether a stool donor program to supply fecal microbiota transplantation (FMT) product is feasible in the Australian regulatory environment. The primary outcome was capacity to supply FMT product. The secondary outcomes were donor eligibility, retention, and output.<br><br>METHODS: Prospective observational cohort study using data collected from the stool donor and FMT production records from BiomeBank, South Australia. Participants were people who engaged with BiomeBank's donor screening and FMT manufacturing process between 01 January 2021 and 31 December 2021.<br><br>RESULTS: In total 176 people registered interest in the program, 74 of 176 (42.0%) proceeded to written questionnaire, 14 of 176 (8.0%) underwent clinical assessment, and 8 of 176 (4.5%) enrolled in the program. Two people were ineligible based on laboratory tests: both had an extended spectrum beta-lactamase producing organism in stool and one also tested positive for hepatitis B core antibody. Two donors remained eligible from 2020, resulting in 10 enrolled donors in 2021; 5 of 10 (50%) male with a median age of 36.9&#x2009;years (interquartile range, 30.3-42.7&#x2009;years). All donors were ineligible to donate at some time point. There were 144 stool donations processed into 1480 50&#x2009;mL FMT; 413 FMT were shipped to 33 Australian hospitals for treatment, 470 for clinical trials, and 89 were destroyed prior to release from quarantine.<br><br>CONCLUSION: Recruitment into the program, retention, and maximizing the yield from a donation period was challenging. Despite this, BiomeBank was able to produce and supply FMT to Australian hospitals under the TGA-regulated Class 2 Biologicals framework.}, }
@article {pmid36968567, year = {2023}, author = {Philips, CA}, title = {"Seek and find" or "search and destroy?" Identifying and retaining "healthy" stool donors for fecal microbiota transplantation.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {7}, number = {3}, pages = {169-171}, pmid = {36968567}, issn = {2397-9070}, }
@article {pmid36965140, year = {2023}, author = {Xu, X and Li, G and Zhang, D and Zhu, H and Liu, GH and Zhang, Z}, title = {Gut Microbiota is Associated with Aging-Related Processes of a Small Mammal Species under High-Density Crowding Stress.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {10}, number = {14}, pages = {e2205346}, pmid = {36965140}, issn = {2198-3844}, support = {32090021//National Natural Science Foundation of China/ ; 32070460//National Natural Science Foundation of China/ ; XDPB16//Strategic Priority Research Program of Chinese Academy of Sciences/ ; 2022081//Youth Innovation Promotion Association of the Chinese Academy of Sciences/ ; }, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Arvicolinae/physiology ; Aging ; Brain ; }, abstract = {Humans and animals frequently encounter high-density crowding stress, which may accelerate their aging processes; however, the roles of gut microbiota in the regulation of aging-related processes under high-density crowding stress remain unclear. In the present study, it is found that high housing density remarkably increases the stress hormone (corticosterone), accelerates aging-related processes as indicated by telomere length (in brain and liver cells) and DNA damage or inflammation (as revealed by tumor necrosis factor-α and interleukin-10 levels), and reduces the lifespan of Brandt's vole (Lasiopodomys brandtii). Fecal microbiota transplantation from donor voles of habitats with different housing densities induces similar changes in aging-related processes in recipient voles. The elimination of high housing density or butyric acid administration delays the appearance of aging-related markers in the brain and liver cells of voles housed at high-density. This study suggests that gut microorganisms may play a significant role in regulating the density-dependent aging-related processes and subsequent population dynamics of animals, and can be used as potential targets for alleviating stress-related aging in humans exposed to high-density crowding stress.}, }
@article {pmid36963238, year = {2023}, author = {Liu, L and Wang, H and Chen, X and Zhang, Y and Zhang, H and Xie, P}, title = {Gut microbiota and its metabolites in depression: from pathogenesis to treatment.}, journal = {EBioMedicine}, volume = {90}, number = {}, pages = {104527}, pmid = {36963238}, issn = {2352-3964}, mesh = {Humans ; *Gastrointestinal Microbiome ; Depression/etiology/therapy ; Dysbiosis/therapy ; *Depressive Disorder, Major/therapy/complications ; *Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Major depressive disorder is one of the most disabling mental disorders worldwide. Increasing preclinical and clinical studies have highlighted that compositional and functional (e.g., metabolite) changes in gut microbiota, known as dysbiosis, are associated with the onset and progression of depression via regulating the gut-brain axis. However, the gut microbiota and their metabolites present a double-edged sword in depression. Dysbiosis is involved in the pathogenesis of depression while, at the same time, offering a novel therapeutic target. In this review, we describe the association between dysbiosis and depression, drug-microbiota interactions in antidepressant treatment, and the potential health benefits of microbial-targeted therapeutics in depression, including dietary interventions, fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and postbiotics. With the emergence of microbial research, we describe a new direction for future research and clinical treatment of depression.}, }
@article {pmid36961604, year = {2023}, author = {Nöltner, C and Bulashevska, A and Hübscher, K and Haberstroh, H and Grimbacher, B and Proietti, M}, title = {Fecal Immunoglobulin Levels as a Modifier of the Gut Microbiome in Patients with Common Variable Immunodeficiency.}, journal = {Journal of clinical immunology}, volume = {43}, number = {6}, pages = {1208-1220}, pmid = {36961604}, issn = {1573-2592}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Common Variable Immunodeficiency ; RNA, Ribosomal, 16S/genetics ; Immunoglobulin A ; Immunoglobulin M ; Feces ; }, abstract = {OBJECTIVE: Common variable immunodeficiency (CVID) is the most common clinically relevant entity of inborn errors of immunity. In these patients, an altered gut microbiome composition with reduced diversity has been described. We sought to investigate the fecal immunoglobulin levels and their impact on the gut microflora in patients with CVID.<br><br>METHODS: We analyzed the gut microbiome of 28 CVID patients and 42 healthy donors (HDs), including 21 healthy household controls, by sequencing the V3 and V4 regions of the bacterial 16S rRNA gene extracted from stool samples. The fecal levels of immunoglobulin A, M, and G of 27 CVID patients and 41 HDs were measured in the supernatant by ELISA and normalized for protein concentration.<br><br>RESULTS: We measured decreased IgA and increased IgG in stool samples from CVID patients compared to HDs. Decreased levels of fecal IgA and IgM were associated with reduced microbial diversity and increased dysbiosis. We identified a large number of significantly differentially abundant taxa, especially in patients with decreased IgA levels, but also in patients with decreased IgM levels compared to their counterparts.<br><br>CONCLUSIONS: CVID patients have an altered gut microbiota composition, which is most prevalent in patients with decreased fecal IgA and IgM levels. In this study, we identify fecal immunoglobulins as a potential modifier of the gut microbiome in CVID patients.}, }
@article {pmid36958092, year = {2023}, author = {Xu, X and Zhuo, L and Zhang, L and Peng, H and Lyu, Y and Sun, H and Zhai, Y and Luo, D and Wang, X and Li, X and Li, L and Zhang, Y and Ma, X and Wang, Q and Li, Y}, title = {Dexmedetomidine alleviates host ADHD-like behaviors by reshaping the gut microbiota and reducing gut-brain inflammation.}, journal = {Psychiatry research}, volume = {323}, number = {}, pages = {115172}, doi = {10.1016/j.psychres.2023.115172}, pmid = {36958092}, issn = {1872-7123}, mesh = {Rats ; Animals ; *Dexmedetomidine/pharmacology/therapeutic use ; *Attention Deficit Disorder with Hyperactivity/drug therapy ; *Gastrointestinal Microbiome ; *Encephalitis ; Rats, Inbred SHR ; Inflammation/drug therapy ; }, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders that affects children and even continues into adulthood. Dexmedetomidine (DEX), a short-term sedative, can selectively activate the α2-adrenoceptor. Treatment with α2-adrenergic agonists in patients with ADHD is becoming increasingly common. However, the therapeutic potential of DEX for the treatment of ADHD is unknown. Here, we evaluated the effect of DEX on ADHD-like behavior in spontaneously hypertensive rats (SHRs), a widely used animal model of ADHD. DEX treatment ameliorated hyperactivity and spatial working memory deficits and normalized θ electroencephalogram (EEG) rhythms in SHRs. We also found that DEX treatment altered the gut microbiota composition and promoted the enrichment of beneficial gut bacterial genera associated with anti-inflammatory effects in SHRs. The gut pathological scores and permeability and the level of inflammation observed in the gut and brain were remarkably improved after DEX administration. Moreover, transplantation of fecal microbiota from DEX-treated SHRs produced effects that mimicked the therapeutic effects of DEX administration. Therefore, DEX is a promising treatment for ADHD that functions by reshaping the composition of the gut microbiota and reducing inflammation in the gut and brain.}, }
@article {pmid36957981, year = {2023}, author = {Stoff, R and Wolf, Y and Boursi, B}, title = {Fecal Microbiota Transplantation as a Cancer Therapeutic.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {29}, number = {2}, pages = {102-108}, doi = {10.1097/PPO.0000000000000651}, pmid = {36957981}, issn = {1540-336X}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects/methods ; *Clostridioides difficile ; *Microbiota ; Treatment Outcome ; *Neoplasms/etiology/therapy ; Carcinogenesis ; Cell Transformation, Neoplastic ; Carcinogens ; }, abstract = {For decades, cancer research and treatment focused on the cellular level, viewing cancer as a genetic disease of cell transformation. In the era of chemotherapy and radiotherapy, studies from the second half of the 19th century suggesting an association between the microbiota and cancer were almost neglected. The main focus of the field was limited to identification of specific viruses and bacteria that may serve as direct carcinogens leading to the recognition of 7 viruses (i.e., human papillomavirus, hepatitis B virus, and Kaposi sarcoma-associated herpesvirus) and 1 bacterium (Helicobacter pylori) as human carcinogens by the International Agency for Research on Cancer (https://monographs.iarc.who.int/agents-classified-by-the-iarc/). Shortly after the publication of the first draft of the human genome project in February 2001, the Nobel laureate microbiologist Joshua Lederberg raised the question: "Is human identity all in the genes?" It took more than a decade later and the development of multiomic techniques to confirm that his answer "each one of us is a small ecological community" was correct (Lederberg J. Keynote Address: Beyond the Genome. Brooklyn Law Rev 67). This ecological notion became relevant to cancer prevention, prediction, and treatment following the immunotherapy revolution and the understanding of the metabolic and immunologic roles of the microbiota in health and disease. Recently, the microbiota was recognized as an emerging hallmark of cancer following a large body of research showing its role in tumorigenesis, treatment efficacy and toxicity, and initial data regarding the role of microbial modulation in cancer therapy (Cancer Discov 2022;12(1):31-46). In the current review, we will focus on the role of fecal microbiota transplantation, the first microbial modulation technique that is used mainly in low-complexity conditions such as recurrent Clostridium difficile infections (Aliment Pharmacol Ther 2017;46(5):479-493), as a possible cancer therapeutic. However, to better understand the suggested roles of fecal microbiota transplantation in medical oncology, we first need to understand cancer as an ecological niche and the role of the microbiota in tumorigenesis and cancer treatment, specifically immunotherapy.}, }
@article {pmid36957977, year = {2023}, author = {Malard, F and Jenq, RR}, title = {The Microbiome and Its Impact on Allogeneic Hematopoietic Cell Transplantation.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {29}, number = {2}, pages = {75-83}, pmid = {36957977}, issn = {1540-336X}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Graft vs Host Disease/etiology/prevention &amp; control ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Microbiota ; Prospective Studies ; }, abstract = {Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to be fully realized is targeting the microbiome to further improve clinical outcomes.In recent years, the intestinal microbiota, which includes bacteria, fungi, viruses, and other microbes that reside within the intestinal tract, has become established as a potent modulator of alloHCT outcomes. The composition of intestinal bacteria, in particular, has been found in large multicenter prospective studies to be strongly associated with GVHD, treatment-related mortality, and overall survival. Murine studies have demonstrated a causal relationship between intestinal microbiota injury and aggravated GVHD, and more recently, clinical interventional studies of repleting the intestinal microbiota with fecal microbiota transplantation have emerged as effective therapies for GVHD. How the composition of the intestinal bacterial microbiota, which is often highly variable in alloHCT patients, can modulate GVHD and other outcomes is not fully understood. Recent studies, however, have begun to make substantial headway, including identifying particular bacterial subsets and/or bacterial-derived metabolites that can mediate harm or benefit. Here, the authors review recent studies that have improved our mechanistic understanding of the relationship between the microbiota and alloHCT outcomes, as well as studies that are beginning to establish strategies to modulate the microbiota with the hope of optimizing clinical outcomes.}, }
@article {pmid36957974, year = {2023}, author = {Myojin, Y and Greten, TF}, title = {The Microbiome and Liver Cancer.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {29}, number = {2}, pages = {57-60}, pmid = {36957974}, issn = {1540-336X}, support = {Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy ; *Microbiota ; *Liver Neoplasms/therapy ; *Gastrointestinal Microbiome ; *Melanoma ; Tumor Microenvironment ; }, abstract = {The gut microbiome and liver are anatomically and functionally connected. The impact of the gut microbiota or microbial metabolites on liver cancer progression via immune cells has been recently revealed across various preclinical models. Commensal gut microbes of liver cancer patients differ from control subjects, and their composition is affected by the etiology of the hepatocellular carcinoma. The gut microbiota represents a potential novel target for intervention as shown in patients with melanoma, but we still lack data in patients with hepatocellular carcinoma. Fecal microbiota transplantation and dietary approaches may improve immunotherapy efficacy, and a couple of clinical trials are ongoing. In liver cancer, the ongoing recognition of interactions between gut microbes and the tumor immune microenvironment provides an exciting therapeutic avenue to complement established immunotherapy.}, }
@article {pmid36951547, year = {2023}, author = {Yang, Q and Wang, B and Zheng, Q and Li, H and Meng, X and Zhou, F and Zhang, L}, title = {A Review of Gut Microbiota-Derived Metabolites in Tumor Progression and Cancer Therapy.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {10}, number = {15}, pages = {e2207366}, pmid = {36951547}, issn = {2198-3844}, support = {2021YFA101000//Ministry of Science and Technology of China/ ; 2022YFA1105200//Ministry of Science and Technology of China/ ; 81973861//Chinese National Natural Science Funds/ ; 31870902//Chinese National Natural Science Funds/ ; 32070907//Chinese National Natural Science Funds/ ; 31871405//Chinese National Natural Science Funds/ ; U20A20393//Chinese National Natural Science Funds/ ; 32125016//National Science Fund for Distinguished Young Scholars/ ; 31925013//National Science Fund for Distinguished Young Scholars/ ; LD19C070001//Zhejiang Natural Science Fund/ ; WKJ-ZJ-2116//Key Construction Project Co-sponsored by Province and Ministry/ ; 2020KY495//General project of Zhejiang Health and Pharmaceutical Science and Technology Plan/ ; 2020ZQ009//Zhejiang Excellent Young Talents Fund for Traditional Chinese Medicine Project/ ; BK20180043//Jiangsu Provincial Distinguished Young Scholars award/ ; 19KJA550003//Key Project of University Natural Science Foundation of Jiangsu Province/ ; //Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; KYCX17_2036//Postgraduate Research &amp; Practice Innovation Program of Jiangsu Province/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota ; *Neoplasms/drug therapy ; *Antineoplastic Agents/therapeutic use/pharmacology ; Immunotherapy ; Tumor Microenvironment ; }, abstract = {Gut microbiota-derived metabolites are key hubs connecting the gut microbiome and cancer progression, primarily by remodeling the tumor microenvironment and regulating key signaling pathways in cancer cells and multiple immune cells. The use of microbial metabolites in radiotherapy and chemotherapy mitigates the severe side effects from treatment and improves the efficacy of treatment. Immunotherapy combined with microbial metabolites effectively activates the immune system to kill tumors and overcomes drug resistance. Consequently, various novel strategies have been developed to modulate microbial metabolites. Manipulation of genes involved in microbial metabolism using synthetic biology approaches directly affects levels of microbial metabolites, while fecal microbial transplantation and phage strategies affect levels of microbial metabolites by altering the composition of the microbiome. However, some microbial metabolites harbor paradoxical functions depending on the context (e.g., type of cancer). Furthermore, the metabolic effects of microorganisms on certain anticancer drugs such as irinotecan and gemcitabine, render the drugs ineffective or exacerbate their adverse effects. Therefore, a personalized and comprehensive consideration of the patient's condition is required when employing microbial metabolites to treat cancer. The purpose of this review is to summarize the correlation between gut microbiota-derived metabolites and cancer, and to provide fresh ideas for future scientific research.}, }
@article {pmid36951545, year = {2023}, author = {Dong, D and Su, T and Chen, W and Wang, D and Xue, Y and Lu, Q and Jiang, C and Ni, Q and Mao, E and Peng, Y}, title = {Clostridioides difficile aggravates dextran sulfate solution (DSS)-induced colitis by shaping the gut microbiota and promoting neutrophil recruitment.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2192478}, pmid = {36951545}, issn = {1949-0984}, mesh = {Mice ; Animals ; *Clostridioides difficile/metabolism ; Dextran Sulfate/toxicity ; *Gastrointestinal Microbiome ; Clostridioides/metabolism ; Neutrophil Infiltration ; *Colitis ; Colon/metabolism ; Inflammation/pathology ; Cytokines/metabolism ; *Inflammatory Bowel Diseases/pathology ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Clostridioides difficile is a pathogen contributing to increased morbidity and mortality of patients with inflammatory bowel disease (IBD). To determine how C. difficile affects the severity of colitis, we constructed a dextran sulfate solution-induced colitis model challenged with C. difficile. Without antibiotic administration, C. difficile led to transient colonization in mice with colitis, but still significantly enhanced disease severity as assessed by weight loss, histopathological damages, and inflammatory cytokine concentrations. Because this effect is independent of toxin production as shown by infection with a non-toxigenic strain, we focused on changes in the gut microbiota. The microbiota altered by C.difficile, featured with reduced proportions of g_Prevotellaceae_UCG-001 and g_Muribaculaceae, were confirmed to contribute to disease severity in colitis mice via fecal microbiota transplantations. The inflamed colon showed neutrophil accumulation by flow cytometric analysis and myeloperoxidase immunochemical staining. There was enrichment of upregulated genes in leukocyte chemotaxis or migration as shown by RNA sequencing analysis. The isolated neutrophils from C. difficile-infected mice with colitis showed a robust migratory ability and had enhanced expression of cytokines and chemokines. We observed a detrimental role of neutrophils in the progress of disease by hindering neutrophil recruitment with the CXCR2 inhibitor SB225002. Furthermore, neutrophil recruitment appeared to be regulated by interleukin (IL)-1β, as inhibition of IL-1β production by MCC950 markedly ameliorated inflammation with decreased neutrophil accumulation and neutrophil-derived chemokine expression. In conclusion, our study provides information on the complicated interaction between microbiota and immune responses in C. difficile-induced inflammation in mice with colitis. Our findings could help determine potential therapeutic targets for patients with IBD concurrent with C. difficile infection.}, }
@article {pmid36949312, year = {2023}, author = {Kim, IB and Park, SC and Kim, YK}, title = {Microbiota-Gut-Brain Axis in Major Depression: A New Therapeutic Approach.}, journal = {Advances in experimental medicine and biology}, volume = {1411}, number = {}, pages = {209-224}, pmid = {36949312}, issn = {0065-2598}, mesh = {Humans ; Depression/therapy ; *Depressive Disorder, Major/therapy ; Brain ; Brain-Gut Axis ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; }, abstract = {Major depression is impacted by the disruption of gut microbiota. Defects in gut microbiota can lead to microbiota-gut-brain axis dysfunction and increased vulnerability to major depression. While traditional chemotherapeutic approaches, such as antidepressant use, produce an overall partial therapeutic effect on depression, the gut microbiome has emerged as an effective target for better therapeutic outcomes. Recent representative studies on the microbiota hypothesis to explore the association between gut pathophysiology and major depression have indicated that restoring gut microbiota and microbiota-gut-brain axis could alleviate depression. We reviewed studies that supported the gut microbiota hypothesis to better understand the pathophysiology of depression; we also explored reports suggesting that gut microbiota restoration is an effective approach for improving depression. These findings indicate that gut microbiota and microbiota-gut-brain axis are appropriate new therapeutic targets for major depression.}, }
@article {pmid36949306, year = {2023}, author = {Evrensel, A}, title = {Microbiome-Induced Autoimmunity and Novel Therapeutic Intervention.}, journal = {Advances in experimental medicine and biology}, volume = {1411}, number = {}, pages = {71-90}, pmid = {36949306}, issn = {0065-2598}, mesh = {Humans ; *Gastrointestinal Microbiome ; Autoimmunity ; *Microbiota ; *Probiotics/therapeutic use ; Prebiotics ; Dysbiosis/therapy/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {Microorganisms' flora, which colonize in many parts of our body, stand out as one of the most important components for a healthy life. This microbial organization called microbiome lives in integration with the body as a single and whole organ/system. Perhaps, the human first encounters the microbial activity it carries through the immune system. This encounter and interaction are vital for the development of immune system cells that protect the body against pathogenic organisms and infections throughout life. In recent years, it has been determined that some disruptions in the host-microbiome interaction play an important role in the physiopathology of autoimmune diseases. Although the details of this interaction have not been clarified yet, the focus is on leaky gut syndrome, dysbiosis, toll-like receptor ligands, and B cell dysfunction. Nutritional regulations, prebiotics, probiotics, fecal microbiota transplantation, bacterial engineering, and vaccination are being investigated as new therapeutic approaches in the treatment of problems in these areas. This article reviews recent research in this area.}, }
@article {pmid36949304, year = {2023}, author = {Shin, C and Kim, YK}, title = {Microbiota-Gut-Brain Axis: Pathophysiological Mechanism in Neuropsychiatric Disorders.}, journal = {Advances in experimental medicine and biology}, volume = {1411}, number = {}, pages = {17-37}, pmid = {36949304}, issn = {0065-2598}, mesh = {Animals ; Humans ; Brain-Gut Axis ; Dysbiosis ; Brain/metabolism ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; *Probiotics ; }, abstract = {Gut microbiota influence human behavior. The immunological, metabolic, and endocrine systems are involved in bidirectional communication between the gut and the brain, which is regulated by microbes through the microbiota-derived neurochemicals and metabolites. Gut microbiota have certain effects on neurodevelopment and maturation of immunity. However, gut dysbiosis can lead to neuropsychiatric disorders. Animal research and clinical case-control studies have demonstrated that gut dysbiosis has an adverse effect on human behavior through a variety of mechanisms. Recent meta-analysis on clinical studies confirmed gut dysbiosis in several major neuropsychiatric disorders. Microbiota-targeted intervention has recently been in the spotlight and meta-analyses have confirmed its effectiveness. In this chapter, we summarize the evidence for the interactions between microbiota and brain-gut network, as well as the potential pathophysiological mechanisms involved.}, }
@article {pmid36948576, year = {2023}, author = {Mishra, SP and Wang, B and Jain, S and Ding, J and Rejeski, J and Furdui, CM and Kitzman, DW and Taraphder, S and Brechot, C and Kumar, A and Yadav, H}, title = {A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut.}, journal = {Gut}, volume = {72}, number = {10}, pages = {1848-1865}, pmid = {36948576}, issn = {1468-3288}, support = {RF1 AG071762/AG/NIA NIH HHS/United States ; R01 AG078153/AG/NIA NIH HHS/United States ; R21 AG072379/AG/NIA NIH HHS/United States ; R56 AG064075/AG/NIA NIH HHS/United States ; R01 AG018915/AG/NIA NIH HHS/United States ; R56 AG069676/AG/NIA NIH HHS/United States ; R01 AG045551/AG/NIA NIH HHS/United States ; U01 AG079828/AG/NIA NIH HHS/United States ; P30 AG021332/AG/NIA NIH HHS/United States ; U01 AG076928/AG/NIA NIH HHS/United States ; U01 HL160272/HL/NHLBI NIH HHS/United States ; }, mesh = {Mice ; Animals ; Humans ; *Gastrointestinal Microbiome ; Mice, Obese ; *Diabetes Mellitus, Experimental ; Inflammation/etiology ; Obesity/complications ; Glucose ; Permeability ; *MicroRNAs ; Ethanolamines ; }, abstract = {OBJECTIVE: Ample evidence exists for the role of abnormal gut microbiota composition and increased gut permeability ('leaky gut') in chronic inflammation that commonly co-occurs in the gut in both obesity and diabetes, yet the detailed mechanisms involved in this process have remained elusive.<br><br>DESIGN: In this study, we substantiate the causal role of the gut microbiota by use of faecal conditioned media along with faecal microbiota transplantation. Using untargeted and comprehensive approaches, we discovered the mechanism by which the obese microbiota instigates gut permeability, inflammation and abnormalities in glucose metabolism.<br><br>RESULTS: We demonstrated that the reduced capacity of the microbiota from both obese mice and humans to metabolise ethanolamine results in ethanolamine accumulation in the gut, accounting for induction of intestinal permeability. Elevated ethanolamine increased the expression of microRNA-miR-101a-3p by enhancing ARID3a binding on the miR promoter. Increased miR-101a-3p decreased the stability of zona occludens-1 (Zo1) mRNA, which in turn, weakened intestinal barriers and induced gut permeability, inflammation and abnormalities in glucose metabolism. Importantly, restoring ethanolamine-metabolising activity in gut microbiota using a novel probiotic therapy reduced elevated gut permeability, inflammation and abnormalities in glucose metabolism by correcting the ARID3a/miR-101a/Zo1 axis.<br><br>CONCLUSION: Overall, we discovered that the reduced capacity of obese microbiota to metabolise ethanolamine instigates gut permeability, inflammation and glucose metabolic dysfunctions, and restoring ethanolamine-metabolising capacity by a novel probiotic therapy reverses these abnormalities.<br><br>TRIAL REGISTRATION NUMBER: NCT02869659 and NCT03269032.}, }
@article {pmid36946907, year = {2023}, author = {Wood, N and Propst, K and Yao, M and Ferrando, CA}, title = {Fecal Microbiota Transfer for Clostridium difficile Infection and Its Effects on Recurrent Urinary Tract Infection.}, journal = {Urogynecology (Philadelphia, Pa.)}, volume = {29}, number = {10}, pages = {814-826}, pmid = {36946907}, issn = {2771-1897}, mesh = {Humans ; Female ; Fecal Microbiota Transplantation ; Retrospective Studies ; Treatment Outcome ; *Clostridioides difficile ; Recurrence ; *Clostridium Infections/epidemiology ; *Urinary Tract Infections/epidemiology ; }, abstract = {IMPORTANCE: Recurrent urinary tract infection (rUTI) poses a significant management challenge, and fecal microbiota transfer (FMT) has been shown in a limited manner to positively effect rUTI.<br><br>OBJECTIVES: The objective of this study was to compare UTI rates after FMT for Clostridium difficile infection (CDI) in patients with previously diagnosed rUTI and patients without a previous diagnosis of rUTI.<br><br>STUDY DESIGN: This was a retrospective cohort study of female patients who underwent FMT between 2015 and 2020 and were identified from a database at a tertiary care referral center. The electronic medical record was queried for demographic and UTI characteristics in the 3 years before and 5 years after FMT, which were compared between patients with or without a preexisting history of rUTI.<br><br>RESULTS: One hundred thirty-five patients were included, 17 of whom had a preexisting history of rUTI. The median number of culture-proven UTIs was 1 in the rUTI group versus 0 in the non-rUTI group both in the 1 year (P = 0.003) and 3 years (P < 0.001) before FMT. Most UTIs before and after FMT were Escherichia coli UTIs (53.8%) and carried some antibiotic resistance (54.6%). Comparatively, in the year after FMT, there were no differences between groups in UTI frequency or antibiotic administration (0 [0-1] vs 0.5 [0-1], P = 0.28). A trend toward decreased frequency of UTI in the 1 year after FMT was seen in the rUTI group. On survival analysis, there was a nonsignificant decrease in the 3-year UTI-free rate for the rUTI group compared with the non-rUTI group (76.5% vs 90.1%, P = 0.07).<br><br>CONCLUSIONS: Patients with recurrent UTI undergoing FMT for recurrent CDI experienced a trend toward a decrease in frequency of UTI after FMT.}, }
@article {pmid36944780, year = {2023}, author = {Oh, M and Zhang, L}, title = {DeepGeni: deep generalized interpretable autoencoder elucidates gut microbiota for better cancer immunotherapy.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {4599}, pmid = {36944780}, issn = {2045-2322}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Neoplasms/therapy ; Precision Medicine ; *Microbiota ; *Melanoma/therapy ; Immunotherapy ; Fecal Microbiota Transplantation ; }, abstract = {Recent studies revealed that gut microbiota modulates the response to cancer immunotherapy and fecal microbiota transplantation has clinical benefits in melanoma patients during treatment. Understanding how microbiota affects individual responses is crucial for precision oncology. However, it is challenging to identify key microbial taxa with limited data as statistical and machine learning models often lose their generalizability. In this study, DeepGeni, a deep generalized interpretable autoencoder, is proposed to improve the generalizability and interpretability of microbiome profiles by augmenting data and by introducing interpretable links in the autoencoder. DeepGeni-based machine learning classifier outperforms state-of-the-art classifier in the microbiome-driven prediction of responsiveness of melanoma patients treated with immune checkpoint inhibitors. Moreover, the interpretable links of DeepGeni elucidate the most informative microbiota associated with cancer immunotherapy response. DeepGeni not only improves microbiome-driven prediction of immune checkpoint inhibitor responsiveness but also suggests potential microbial targets for fecal microbiota transplant or probiotics improving the outcome of cancer immunotherapy.}, }
@article {pmid36943918, year = {2023}, author = {Kharofa, J and Haslam, D and Wilkinson, R and Weiss, A and Patel, S and Wang, K and Esslinger, H and Olowokure, O and Sohal, D and Wilson, G and Ahmad, S and Apewokin, S}, title = {Analysis of the fecal metagenome in long-term survivors of pancreas cancer.}, journal = {Cancer}, volume = {129}, number = {13}, pages = {1986-1994}, doi = {10.1002/cncr.34748}, pmid = {36943918}, issn = {1097-0142}, support = {K08 CA237735/CA/NCI NIH HHS/United States ; }, mesh = {Verrucomicrobia ; Feces ; *Pancreatic Neoplasms/genetics/therapy ; *Metagenome ; Cross-Sectional Studies ; Akkermansia ; Humans ; Survivors ; }, abstract = {BACKGROUND: The 5-year overall survival of pancreas adenocarcinoma (PCa) remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long-term survivors (LTSs) from unselected patients. Preclinical studies using fecal transplant experiments from LTSs of PCa have revealed delayed tumor growth through unknown mechanisms involving the fecal microbiota. However, features of the fecal microbiome in patients with long-term survival are not well described.<br><br>METHODS: In this cross-sectional study, comprehensive shotgun metagenomics was performed on stool from PCa patients with long-term survival (n&#xa0;=&#xa0;16). LTS was defined as >4&#xa0;years from pancreatectomy and all therapy without recurrence. LTSs were compared to control patients with PCa who completed pancreatectomy and chemotherapy (n&#xa0;=&#xa0;8). Stool was sequenced using an Illumina NextSeq500. Statistical analyses were performed in R with MicrobiomeSeq and Phyloseq for comparison of LTSs and controls.<br><br>RESULTS: All patients underwent pancreatectomy and chemotherapy before sample donation. The median time from pancreatectomy of 6&#xa0;years (4-14&#xa0;years) for LTSs without evidence of disease compared to a median disease-free survival of 1.8&#xa0;years from pancreatectomy in the control group. No differences were observed in overall microbial diversity for LTSs and controls using Shannon/Simpson indexes. Significant enrichment of species relative abundance was observed in LTSs for the Ruminococacceae family specifically Faecalibacterium prausnitzii species as well as Akkermansia muciniphila species.<br><br>CONCLUSIONS: Stool from patients cured from PCa has more relative abundance of Faecalibacterium prausnitzii and Akkermansia muciniphila. Additional studies are needed to explore potential mechanisms by which the fecal microbiota may influence survival in PCa.<br><br>PLAIN LANGUAGE SUMMARY: Although pancreatic cancer treatments have improved, the number of long-term survivors has remained stagnant with a 5-year overall survival estimate of 9%. Emerging evidence suggests that microbes within the gastrointestinal tract can influence cancer response through activation of the immune system. In this study, we profiled the stool microbiome in long-term survivors of pancreas cancer and controls. Several enriched species previously associated with enhanced tumor immune response were observed including Faecalibacterium prausnitzii and Akkermansia muciniphila. These findings warrant additional study assessing mechanisms by which the fecal microbiota may enhance pancreatic cancer immune response.}, }
@article {pmid36942967, year = {2023}, author = {Shi, YT and He, JM and Tong, ZA and Qian, YJ and Wang, QW and Jia, DJC and Zhu, WJ and Zhao, YX and Cai, BB and Chen, SJ and Si, MS}, title = {Ligature-Induced Periodontitis Drives Colorectal Cancer: An Experimental Model in Mice.}, journal = {Journal of dental research}, volume = {102}, number = {6}, pages = {689-698}, doi = {10.1177/00220345231158269}, pmid = {36942967}, issn = {1544-0591}, mesh = {Mice ; Animals ; *Periodontitis/microbiology ; Bacteria/genetics ; *Gastrointestinal Microbiome ; *Colorectal Neoplasms/complications ; Disease Models, Animal ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Periodontitis is a prevalent inflammatory oral disease associated with an increased risk of colorectal cancer. Experimental animal models are critical tools to investigate the effects and mechanisms of periodontitis on colorectal cancer. Several murine periodontitis models have been used in research, including oral gavage, periodontal pathogen injection, and ligature models. The role of experimental periodontitis caused by silk ligation in colorectal cancer remains unclear. In this study, we used an experimental periodontitis model on a colitis-associated colorectal cancer model and a spontaneous model, respectively. We observed the promotion of colorectal cancer in ligature-induced periodontitis mice compared to those control mice in 2 different models, as assessed by tumor number, tumor size, and tumor load. Since bacterial dysbiosis is an important feature of periodontitis, we next analyzed the oral and gut microbiomes using 16S ribosomal RNA gene sequencing. We found that the experimental periodontitis model reshaped the microbial community in the oral cavity and gut. In addition, we found a higher extent of programmed death 1 (PD-1)-positive CD8[+] T-cell infiltration in tumor samples of the periodontitis group than in controls by immunofluorescence staining. Regarding the potential molecular mechanism, we transplanted the fecal microbiota of the periodontitis patient into mice and observed a tumor-promoting effect in the periodontitis group, assessed by tumor volume and tumor weight, together with a low level of INF-γ[+] CD8[+] T-cell infiltration in subcutaneous tumor mice. Taken together, we show that ligature-induced periodontitis model promotes colorectal cancer by microbiota remodeling and suppression of the immune response.}, }
@article {pmid36940999, year = {2023}, author = {Jiang, S and Shen, B}, title = {[Research progress on the relationship between gut microbiota dysbiosis and osteoarthritis].}, journal = {Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery}, volume = {37}, number = {3}, pages = {371-376}, pmid = {36940999}, issn = {1002-1892}, mesh = {Humans ; *Dysbiosis/therapy ; *Gastrointestinal Microbiome ; Inflammation ; *Osteoarthritis ; Probiotics/therapeutic use ; }, abstract = {OBJECTIVE: To introduce the research progress on the relationship between gut microbiota dysbiosis and osteoarthritis (OA), focus on the possible mechanism of gut microbiota dysbiosis promoting OA, and propose a new therapeutic direction.<br><br>METHODS: The domestic and foreign research literature on the relationship between gut microbiota dysbiosis and OA was reviewed. The role of the former in the occurrence and development of OA and the new ideas for the treatment of OA were summarized.<br><br>RESULTS: The gut microbiota dysbiosis promotes the development of OA mainly in three aspects. First, the gut microbiota dysbiosis destroys intestinal permeability and causes low-grade inflammation, which aggravate OA. Secondly, the gut microbiota dysbiosis promotes the development of OA through metabolic syndrome. Thirdly, the gut microbiota dysbiosis is involved in the development of OA by regulating the metabolism and transport of trace elements. Studies have shown that improving gut microbiota dysbiosis by taking probiotics and transplanting fecal microbiota can reduce systemic inflammation and regulate metabolic balance, thus treating OA.<br><br>CONCLUSION: Gut microbiota dysbiosis is closely related to the development of OA, and improving gut microbiota dysbiosis can be an important idea for OA treatment.}, }
@article {pmid36938601, year = {2023}, author = {Br, VK and Sarin, SK}, title = {Acute-on-chronic liver failure: Terminology, mechanisms and management.}, journal = {Clinical and molecular hepatology}, volume = {29}, number = {3}, pages = {670-689}, pmid = {36938601}, issn = {2287-285X}, mesh = {Humans ; Severity of Illness Index ; *Acute-On-Chronic Liver Failure/diagnosis/therapy/etiology ; *End Stage Liver Disease ; Prognosis ; *Hepatic Encephalopathy/complications ; }, abstract = {Acute-on-chronic liver failure is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high probability of extrahepatic organ involvement and high 28-day mortality. The pathogenesis involves extensive hepatic necrosis, which is associated with severe systemic inflammation and subsequently causes the cytokine storm, leading to portal hypertension, organ dysfunction, and organ failure. These patients have increased gut permeability, releasing lipopolysaccharide (LPS) and damage-associated molecular patterns (DAMPS) in the blood, leading to hyper-immune activation and the secretion of cytokines, followed by immune paralysis, causing the development of infections and organ failure in a proportion of patients. Early detection and the institution of treatment, especially in the "Golden Window" period of 7 days, gives an opportunity for reversal of the syndrome. Scores like the Asian Pacific Association for the Study of the Liver (APASL) ACLF research consortium (AARC) score, a model for end stage liver disease (MELD), and the CLIF Consortium acute-on-chronic liver failure (CLIF-C ACLF) score can help in the prediction of mortality. Treatment strategy includes treatment of acute insult. Patients should be considered for early transplant with MELD score >28, AARC score >10, high-grade hepatic encephalopathy, and in the absence of >2 organ failure or overt sepsis to improve survival of up to 80% at five years. Patients, with no option of transplant, can be treated with emerging therapies like faecal microbial transplant, plasma exchange, etc., which need further evaluation.}, }
@article {pmid36938236, year = {2023}, author = {Wynn, AB and Beyer, G and Richards, M and Ennis, LA}, title = {Procedure, Screening, and Cost of Fecal Microbiota Transplantation.}, journal = {Cureus}, volume = {15}, number = {2}, pages = {e35116}, pmid = {36938236}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) is currently considered a potential treatment for various GI-related illnesses, with the goal to replenish natural healthy flora of the GI tract that has been harmed because of antibiotic use or overgrowth of harmful bacteria. Current methods of administering the processed stool include colonoscopy and enema, while an oral capsule is being developed. Each method of administration carries its own set of risks, including adverse reactions to treatment, infection following the invasive administration procedure, and flare-ups of GI-related symptoms. Current oral administration through nasoduodenal tube poses a risk for aspiration which has not been ruled out as the cause of subsequent pneumonia and death in patient trials. The development of an oral capsule could address some of the faults of the current methods, not only making treatment more affordable and accessible but also less of a risk due to its minimally invasive nature. FMT is also a treatment option to attenuate adverse effects associated with antibiotic use, including combatting the emergence of antibiotic resistance, as well as adverse effects related to other medical treatments such as chemotherapy. While FMT is an unexplored treatment option for multiple gastrointestinal disorders and is currently still largely inaccessible for many patients financially, studies have suggested that it could be a more affordable treatment option long-term for patients as aspects of the treatment become more affordable with further research.}, }
@article {pmid36938160, year = {2023}, author = {Spartz, EJ and Estafanos, M and Mallick, R and Gaertner, W and Vakayil, V and Jahansouz, C and Aggarwal, R and Ikramuddin, S and Khoruts, A and Harmon, JV}, title = {Fecal Microbiota Transplantation for Fulminant Clostridioides Difficile Infection: A Combined Medical and Surgical Case Series.}, journal = {Cureus}, volume = {15}, number = {2}, pages = {e34998}, pmid = {36938160}, issn = {2168-8184}, abstract = {Urgent abdominal colectomy is indicated for patients with fulminant Clostridioides difficile infection (CDI) when other medical therapies fail, yet mortality remains high. Fecal microbiota transplant is a less invasive alternative approach for patients with fulminant CDI. We report the 30-day complications of patients with fulminant CDI who underwent either abdominal colectomy, fecal microbiota transplantation (FMT), or FMT followed by abdominal colectomy (FMT-CO). Methods: We performed a single-center, retrospective case review of combined medical and surgical patients with CDI at a large academic medical center between 2008 and 2016. Cohorts were identified as patients with fulminant CDI who underwent total abdominal colectomy alone (CO), FMT alone (FMT), or FMT-CO. We analyzed patient demographics, history, comorbidities, clinical and laboratory variables, CDI severity scores, and mortality outcomes at 30 days. Results: We identified 5,150 patients with CDI at our center during the review period; 16 patients met the criteria for fulminant CDI and were included in this study, with four patients in the CO cohort, eight patients in the FMT cohort, and four patients in the FMT-CO cohort. Demographics and CDI severity scores were similar for all three groups, although the selected comorbidity profiles differed significantly among the three cohorts. The 30-day mortality rates for patients in the CO, FMT, and FMT-CO groups were 25%, 12.5%, and 25%, respectively. Conclusions: FMT is an alternative or adjunctive therapy to colectomy for patients with fulminant CDI that is not associated with increased mortality. Implementation of FMT protocols in clinical practice would be dependent on the availability of qualified transplant material and successful early identification of patients likely to benefit from FMT.}, }
@article {pmid36937721, year = {2023}, author = {Zhang, J and Zhu, G and Wan, L and Liang, Y and Liu, X and Yan, H and Zhang, B and Yang, G}, title = {Effect of fecal microbiota transplantation in children with autism spectrum disorder: A systematic review.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1123658}, pmid = {36937721}, issn = {1664-0640}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) may be helpful in the treatment of autism spectrum disorder (ASD) as rebalancing the gut microbiome has been shown to potentially improve behavioral symptoms in children with ASD.<br><br>METHODS: This systematic review was conducted to assess the effect of FMT for children with ASD. The Embase, PubMed, Web of Science, and Cochrane Library databases were searched for articles published from inception to October 6, 2022. Two reviewers independently screened the identified records and undertook data extraction.<br><br>RESULTS: The search identified a total of five studies: two prospective open-label studies, two retrospective observational studies, and a case report; however, no randomized controlled trial was identified. All five studies reported a significant post-FMT-treatment improvement in neuropsychological assessment of ASD. The two prospective open-label studies suggested that the Autism Behavior Checklist (ABC) score, and the Social Responsiveness Scale (SRS) score at the posttreatment assessment decreased from the baseline (Wilcoxon signed-rank test; all p < 0.01]). The two retrospective observational studies suggested that FMT helped to improve the ASD symptoms. One observational study reported that the Childhood Autism Rating Scale (CARS) score and ABC score of the constipation group decreased from the baseline after the second course assessment (CARS [baseline: mean 35.25 &#xb1; standard deviation 4.36, second course: 32.5 &#xb1; 3.1, p = 0.015]; ABC [baseline: 56.21 &#xb1; 16.08, second course: 46.54 &#xb1; 16.54, p = 0.046]). Another observational study found that both ABC and CARS scores decreased as the number of FMT courses increased, and significant differences were found at the end of each course as compared with the baseline.<br><br>CONCLUSION: Compared with the baseline, FMT significantly improved symptoms of autism in children with ASD in observational studies. However, rigorously designed randomized controlled clinical trials are needed to establish the safety and efficacy of FMT as a treatment for ASD.}, }
@article {pmid36937662, year = {2023}, author = {Wang, J and Liu, X and Li, Q}, title = {Interventional strategies for ischemic stroke based on the modulation of the gut microbiota.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1158057}, pmid = {36937662}, issn = {1662-4548}, abstract = {The microbiota-gut-brain axis connects the brain and the gut in a bidirectional manner. The organism's homeostasis is disrupted during an ischemic stroke (IS). Cerebral ischemia affects the intestinal flora and microbiota metabolites. Microbiome dysbiosis, on the other hand, exacerbates the severity of IS outcomes by inducing systemic inflammation. Some studies have recently provided novel insights into the pathogenesis, efficacy, prognosis, and treatment-related adverse events of the gut microbiome in IS. In this review, we discussed the view that the gut microbiome is of clinical value in personalized therapeutic regimens for IS. Based on recent non-clinical and clinical studies on stroke, we discussed new therapeutic strategies that might be developed by modulating gut bacterial flora. These strategies include dietary intervention, fecal microbiota transplantation, probiotics, antibiotics, traditional Chinese medication, and gut-derived stem cell transplantation. Although the gut microbiota-targeted intervention is optimistic, some issues need to be addressed before clinical translation. These issues include a deeper understanding of the potential underlying mechanisms, conducting larger longitudinal cohort studies on the gut microbiome and host responses with multiple layers of data, developing standardized protocols for conducting and reporting clinical analyses, and performing a clinical assessment of multiple large-scale IS cohorts. In this review, we presented certain opportunities and challenges that might be considered for developing effective strategies by manipulating the gut microbiome to improve the treatment and prevention of ischemic stroke.}, }
@article {pmid36937520, year = {2023}, author = {DuPont, HL and Suescun, J and Jiang, ZD and Brown, EL and Essigmann, HT and Alexander, AS and DuPont, AW and Iqbal, T and Utay, NS and Newmark, M and Schiess, MC}, title = {Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1104759}, pmid = {36937520}, issn = {1664-2295}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND AND PURPOSE: The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease.<br><br>METHODS: This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months).<br><br>RESULTS: Fecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks (p = 0.008) and 13 weeks (p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index (p = 0.0374) were improved in the FMT group.<br><br>CONCLUSIONS: Subjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms.<br><br>CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, identifier: NCT03671785.}, }
@article {pmid36936775, year = {2023}, author = {Fourati, S and Dumay, A and Roy, M and Willemetz, A and Ribeiro-Parenti, L and Mauras, A and Mayeur, C and Thomas, M and Kapel, N and Joly, F and Le Gall, M and Bado, A and Le Beyec, J}, title = {Fecal microbiota transplantation in a rodent model of short bowel syndrome: A therapeutic approach?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1023441}, pmid = {36936775}, issn = {2235-2988}, mesh = {Rats ; Animals ; *Short Bowel Syndrome/therapy/microbiology/pathology ; Rodentia ; Fecal Microbiota Transplantation ; Intestinal Mucosa/pathology ; Jejunum ; }, abstract = {Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic intestinal failure. Colon preservation is crucial for spontaneous adaptation, to improve absorption and reduce parenteral nutrition dependence. Fecal microbiota transplantation (FMT), a promising approach in pathologies with dysbiosis as the one observed in SBS patients, was assessed in SBS rats with jejuno-colonic anastomosis. The evolution of weight and food intake, the lenght of intestinal villi and crypts and the composition of fecal microbiota of Sham and SBS rats, transplanted or not with high fat diet rat microbiota, were analyzed. All SBS rats lost weight, increased their food intake and exhibited jejunal and colonic hyperplasia. Microbiota composition of SBS rats, transplanted or not, was largely enriched with Lactobacillaceae, and α- and β-diversity were significantly different from Sham. The FMT altered microbiota composition and α- and β-diversity in Sham but not SBS rats. FMT from high fat diet rats was successfully engrafted in Sham, but failed to take hold in SBS rats, probably because of the specific luminal environment in colon of SBS subjects favoring aero-tolerant over anaerobic bacteria. Finally, the level of food intake in SBS rats was positively correlated with their Lactobacillaceae abundance. Microbiota transfer must be optimized and adapted to this specific SBS environment.}, }
@article {pmid36934020, year = {2023}, author = {Berthouzoz, E and Lazarevic, V and Zekeridou, A and Castro, M and Debove, I and Aybek, S and Schrenzel, J and Burkhard, PR and Fleury, V}, title = {Oral and intestinal dysbiosis in Parkinson's disease.}, journal = {Revue neurologique}, volume = {179}, number = {9}, pages = {937-946}, doi = {10.1016/j.neurol.2022.12.010}, pmid = {36934020}, issn = {0035-3787}, mesh = {Animals ; Humans ; *Parkinson Disease/complications/therapy/metabolism ; Dysbiosis/complications/metabolism ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Inflammation/complications ; }, abstract = {The suspicion of an origin of Parkinson's disease (PD) at the periphery of the body and the involvement of environmental risk factors in the pathogenesis of PD have directed the attention of the scientific community towards the microbiota. The microbiota represents all the microorganisms residing both in and on a host. It plays an essential role in the physiological functioning of the host. In this article, we review the dysbiosis repeatedly demonstrated in PD and how it influences PD symptoms. Dysbiosis is associated with both motor and non-motor PD symptoms. In animal models, dysbiosis only promotes symptoms in individuals genetically susceptible to Parkinson's disease, suggesting that dysbiosis is a risk factor but not a cause of Parkinson's disease. We also review how dysbiosis contributes to the pathophysiology of PD. Dysbiosis induces numerous and complex metabolic changes, resulting in increased intestinal permeability, local and systemic inflammation, production of bacterial amyloid proteins that promote α-synuclein aggregation, as well as a decrease in short-chain fatty acid-producing bacteria that have anti-inflammatory and neuroprotective potential. In addition, we review how dysbiosis decreases the efficacy of dopaminergic treatments. We then discuss the interest of dysbiosis analysis as a biomarker of Parkinson's disease. Finally, we give an overview of how interventions modulating the gut microbiota such as dietary interventions, pro-biotics, intestinal decontamination and fecal microbiota transplantation could influence the course of PD.}, }
@article {pmid36931952, year = {2023}, author = {Lin, L and Zhang, K and Xiong, Q and Zhang, J and Cai, B and Huang, Z and Yang, B and Wei, B and Chen, J and Niu, Q}, title = {Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression.}, journal = {Journal of autoimmunity}, volume = {141}, number = {}, pages = {103001}, doi = {10.1016/j.jaut.2023.103001}, pmid = {36931952}, issn = {1095-9157}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Arthritis, Rheumatoid ; *Autoimmune Diseases ; Inflammation ; *MicroRNAs ; }, abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA is a prolonged state before clinical arthritis and RA develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due to the breakdown of immunologic self-tolerance. As early treatment initiation before the onset of polyarthritis may achieve sustained remission, optimize clinical outcomes, and even prevent RA progression, the pre-clinical RA stage is showing the prospect to be the window of opportunity for RA treatment. Growing evidence has shown the role of the gut microbiota in inducing systemic inflammation and polyarthritis via multiple mechanisms, which may involve molecular mimicry, impaired intestinal barrier function, gut microbiota-derived metabolites mediated immune regulation, modulation of the gut microbiota's effect on immune cells, intestinal epithelial cells autophagy, and the interaction between the microbiome and human leukocyte antigen alleles as well as microRNAs. Since gut microbiota alterations in pre-clinical RA have been reported, potential therapies for modifying the gut microbiota in pre-clinical RA, including natural products, antibiotic therapy, fecal microbiota transplantation, probiotics, microRNAs therapy, vitamin D supplementation, autophagy inducer-based treatment, prebiotics, and diet, holds great promise for the successful treatment and even prevention of RA via altering ongoing inflammation. In this review, we summarized current studies that include pathogenesis of gut microbiota in RA progression and promising therapeutic strategies to provide novel ideas for the management of pre-clinical RA and possibly preventing arthritis progression.}, }
@article {pmid36931236, year = {2023}, author = {Walter, J and Shanahan, F}, title = {Fecal microbiota-based treatment for recurrent Clostridioides difficile infection.}, journal = {Cell}, volume = {186}, number = {6}, pages = {1087}, doi = {10.1016/j.cell.2023.02.034}, pmid = {36931236}, issn = {1097-4172}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridioides difficile ; Feces ; *Clostridium Infections/therapy ; *Microbiota ; Recurrence ; }, abstract = {Rebyota is a rectally administered fecal microbiota suspension for prevention of recurrence of Clostridioides difficile infection. The mechanism of action of Rebyota probably involves competitive exclusion of C. difficile by donor microbes with reduced toxin production; other factors may include restoration of protective taxa and modulation of the recipient's microbiome by phage, donor microbes, or metabolites.}, }
@article {pmid36930488, year = {2023}, author = {Bellucci, E and Chiereghin, F and Pacifici, F and Donadel, G and De Stefano, A and Malatesta, G and Valente, MG and Guadagni, F and Infante, M and Rovella, V and Noce, A and Tesauro, M and Di Daniele, N and Della Morte, D and Pastore, D}, title = {Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {5}, pages = {1921-1944}, doi = {10.26355/eurrev_202303_31558}, pmid = {36930488}, issn = {2284-0729}, mesh = {Animals ; Humans ; *Non-alcoholic Fatty Liver Disease/metabolism ; Dysbiosis/therapy ; *Diabetes Mellitus, Type 2/pathology ; *Gastrointestinal Microbiome ; Inflammation/pathology ; *Insulins ; Liver/pathology ; }, abstract = {The growing global epidemic of obesity and type 2 diabetes mellitus has determined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the Western world and a leading cause of liver transplantation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close association between insulin resistance (IR), dysbiosis, and steatosis. However, all the mechanisms that lead to impaired permeability, inflammation, and fibrosis have not been fully clarified. Recently, new possible treatment modalities have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (polyphenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NAFLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the therapeutic strategies currently in use.}, }
@article {pmid36928160, year = {2023}, author = {Bhatt, A and Haslam, A and Prasad, V}, title = {The effect of gastrointestinal microbiome supplementation on immune checkpoint inhibitor immunotherapy: a systematic review.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {10}, pages = {7355-7362}, pmid = {36928160}, issn = {1432-1335}, mesh = {Humans ; *Nivolumab/therapeutic use ; Ipilimumab ; Immune Checkpoint Inhibitors/therapeutic use ; *Gastrointestinal Microbiome ; Retrospective Studies ; Immunotherapy ; }, abstract = {PURPOSE: Gastrointestinal (GI) microbiome modulators, such as fecal microbiome transplants (FMTs), are being considered as supplements to standard immune checkpoint inhibitor (ICI) treatment to improve efficacy. This systematic review aims to assess the study design and outcomes of clinical trials that use FMTs to enhance ICI treatment.<br><br>METHODS: Systematic literature searches were conducted on PubMed and Embase using search terms that included names of ICIs and gastrointestinal microbiome. A first search identified interventional trials, and the second search identified interventional, retrospective, and observational studies.<br><br>RESULTS: The search for interventional trials produced 205 articles, 3&#xa0;of which met the inclusion criteria. All studies had sample sizes ranging between 10 and 30 participants. 2 of the studies were single-arm studies with no control&#xa0;arm. One study reported an overall response rate (ORR) of 3 out of 15 (20%), a median progression-free survival (PFS) of 3&#xa0;months, and a median overall survival (OS) of 7&#xa0;months. The second study reported 1 complete response out of 10 (10%) and 2 partial responses out of 10 (20%). The third study reported an ORR of 58% vs. 20%, a median PFS of 12.7&#xa0;months vs. 2.5&#xa0;months in patients receiving nivolumab-ipilimumab plus CBM588 compared with patients receiving nivolumab-ipilimumab alone respectively, and an undefined median OS.<br><br>CONCLUSION: Current studies on the microbiome modulators with ICI use are limited in study design. Future clinical trials should be randomized, use larger sample sizes, and use an appropriate control arm to better ascertain the clinical effect of the GI microbiome on ICI treatment.}, }
@article {pmid36927795, year = {2023}, author = {Yi, X and Huang, C and Huang, C and Zhao, M and Lu, Q}, title = {Fecal microbiota from MRL/lpr mice exacerbates pristane-induced lupus.}, journal = {Arthritis research &amp; therapy}, volume = {25}, number = {1}, pages = {42}, pmid = {36927795}, issn = {1478-6362}, mesh = {Mice ; Animals ; Mice, Inbred MRL lpr ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Feces ; *Lupus Erythematosus, Systemic/chemically induced ; }, abstract = {BACKGROUND: The roles of gut microbiota in the pathogenesis of SLE have been receiving much attention during recent years. However, it remains unknown how fecal microbiota transplantation (FMT) and microbial metabolites affect immune responses and lupus progression.<br><br>METHODS: We transferred fecal microbiota from MRL/lpr (Lpr) mice and MRL/Mpj (Mpj) mice or PBS to pristane-induced lupus mice and observed disease development. We also screened gut microbiota and metabolite spectrums of pristane-induced lupus mice with FMT via 16S rRNA sequencing, metagenomic sequencing, and metabolomics, followed by correlation analysis.<br><br>RESULTS: FMT from MRL/lpr mice promoted the pathogenesis of pristane-induced lupus and affected immune cell profiles in the intestine, particularly the plasma cells. The structure and composition of microbial communities in the gut of the FMT-Lpr mice were different from those of the FMT-Mpj mice and FMT-PBS mice. The abundances of specific microbes such as prevotella taxa were predominantly elevated in the gut microbiome of the FMT-Lpr mice, which were positively associated with functional pathways such as cyanoamino acid metabolism. Differential metabolites such as valine and L-isoleucine were identified with varied abundances among the three groups. The abundance alterations of the prevotella taxa may affect the phenotypic changes such as proteinuria levels in the pristane-induced lupus mice.<br><br>CONCLUSION: These findings further confirm that gut microbiota play an important role in the pathogenesis of lupus. Thus, altering the gut microbiome may provide a novel way to treat lupus.}, }
@article {pmid36926604, year = {2023}, author = {Shin, YJ and Lee, DY and Kim, JY and Heo, K and Shim, JJ and Lee, JL and Kim, DH}, title = {Effect of fermented red ginseng on gut microbiota dysbiosis- or immobilization stress-induced anxiety, depression, and colitis in mice.}, journal = {Journal of ginseng research}, volume = {47}, number = {2}, pages = {255-264}, pmid = {36926604}, issn = {1226-8453}, abstract = {BACKGROUND: Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-β-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice.<br><br>METHODS: Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests.<br><br>RESULTS: Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF[+]NeuN[+] cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-&#x3b1; levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased.<br><br>CONCLUSION: Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.}, }
@article {pmid36925044, year = {2023}, author = {Baldanzi, G and Sayols-Baixeras, S and Theorell-Haglöw, J and Dekkers, KF and Hammar, U and Nguyen, D and Lin, YT and Ahmad, S and Holm, JB and Nielsen, HB and Brunkwall, L and Benedict, C and Cedernaes, J and Koskiniemi, S and Phillipson, M and Lind, L and Sundström, J and Bergström, G and Engström, G and Smith, JG and Orho-Melander, M and Ärnlöv, J and Kennedy, B and Lindberg, E and Fall, T}, title = {OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study.}, journal = {Chest}, volume = {164}, number = {2}, pages = {503-516}, pmid = {36925044}, issn = {1931-3543}, mesh = {Adult ; Animals ; Humans ; *Sleep Apnea, Obstructive ; *Gastrointestinal Microbiome ; Cross-Sectional Studies ; Sweden/epidemiology ; Hypoxia ; }, abstract = {BACKGROUND: OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism.<br><br>RESEARCH QUESTION: Does OSA in adults associate with the composition and functional potential of the human gut microbiota?<br><br>STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.<br><br>RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.<br><br>INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.}, }
@article {pmid36924566, year = {2023}, author = {Jiang, X and Liu, Z and Ma, Y and Miao, L and Zhao, K and Wang, D and Wang, M and Ruan, H and Xu, F and Zhou, Q and Xu, S}, title = {Fecal microbiota transplantation affects the recovery of AD-skin lesions and enhances gut microbiota homeostasis.}, journal = {International immunopharmacology}, volume = {118}, number = {}, pages = {110005}, doi = {10.1016/j.intimp.2023.110005}, pmid = {36924566}, issn = {1878-1705}, mesh = {Animals ; Mice ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Dermatitis, Atopic/therapy ; RNA, Ribosomal, 16S/genetics ; Cytokines ; Homeostasis ; Feces/microbiology ; }, abstract = {BACKGROUND: Accumulating evidence has shown that gut microbiota plays a key role in the progression of atopic dermatitis (AD). Fecal microbiota transplantation (FMT), as an effective method to restore gut microbiota homeostasis, has been successfully applied for treating many inflammatory diseases. However, the therapeutic effect of FMT on AD remains unclear. The following study examined the effect and mechanism of FMT on AD-skin lesions in an AD mouse model.<br><br>METHODS: In this study, we exposed the shaved back skin of BALB/c mice to calcipotriol (MC903) to induce AD model. Mice were then treated with FMT, which was performed with gut microbiota from healthy mice. The gut microbiota of treated mice was tracked by 16S rRNA gene sequencing. Mice skin tissues were examined by histopathology and inflammatory cytokines change in serum by ELISA.<br><br>RESULTS: FMT had a faster trend on the reversion of the increases in skin epidermal layer thicknesses and suppressed some of the representative inflammatory cytokines. The gut microbial community in the natural recovery process varied significantly in the FMT group at day 7 (ANOSIM P&#xa0;=&#xa0;0.0229, r&#xa0;=&#xa0;0.2593). Notably, FMT had a long-lasting and beneficial impact on the gut microbial compositions of AD mice by increasing the ratio of Firmicutes to Bacteroidetes and the amount of butyric-producing bacteria (BPB), including Erysipelotrichaceae, Lactobacillaceae, and Eubacteriacea. Furthermore, the relative abundances of gut microbiota-mediated functional pathways involved in the cell growth and death, amino acid, energy, lipid, and carbohydrate metabolisms, and immune system increased after FMT treatment.<br><br>CONCLUSION: FMT modulated the gut microbiota homeostasis and affected the recovery from AD-related inflammations, suggesting that it could be used as a treatment strategy for AD patients in the clinic.}, }
@article {pmid36923929, year = {2023}, author = {Shim, JA and Ryu, JH and Jo, Y and Hong, C}, title = {The role of gut microbiota in T cell immunity and immune mediated disorders.}, journal = {International journal of biological sciences}, volume = {19}, number = {4}, pages = {1178-1191}, pmid = {36923929}, issn = {1449-2288}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; T-Lymphocytes ; *Microbiota ; *Autoimmune Diseases ; Inflammation ; }, abstract = {Gut microbiota was only considered as a commensal organism that aids in digestion, but recent studies revealed that the microbiome play a critical role in both physiological and pathological immune system. The gut microbiome composition is altered by environmental factors such as diet and hygiene, and the alteration affects immune cells, especially T cells. Advanced genomic techniques in microbiome research defined that specific microbes regulate T cell responses and the pathogenesis of immune-mediated disorders. Here, we review features of specific microbes-T cell crosstalk and relationship between the microbes and immunopathogenesis of diseases including in cancers, autoimmune disorders and allergic inflammations. We also discuss the limitations of current experimental animal models, cutting-edge developments and current challenges to overcome in the field, and the possibility of considering gut microbiome in the development of new drug.}, }
@article {pmid36923594, year = {2023}, author = {Chen, P and Wang, K and Zhuang, M and Fu, X and Liu, S and Chen, M and Lei, Y}, title = {An insight into gut microbiota and metabolites in the mice with adenomyosis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1075387}, pmid = {36923594}, issn = {2235-2988}, mesh = {Humans ; Mice ; Female ; Animals ; *Gastrointestinal Microbiome/genetics ; Metabolome ; *Adenomyosis ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred ICR ; Feces/chemistry ; Bacteroidetes/genetics ; }, abstract = {BACKGROUND: Adenomyosis (AM) is a benign uterine disease characterized pathologically by the invasion of endometrial tissue into the myometrium. The pathogenesis of AM is still far from clear. Although the gut microbiome and metabolomics are thought to contribute to a variety of diseases, the role of them in AM has not been revealed.<br><br>OBJECTIVE: To investigate changes in the gut microbiota and derived metabolites in AM mice.<br><br>METHOD: Female ICR mice were randomly assigned to AM and control groups, and pituitary transplantation was employed to perform AM modeling. Then, the fecal samples were obtained for microbial (16S rRNA gene sequencing) and metabolomic (liquid chromatography mass spectrometry, LC-MS) analysis.<br><br>RESULT: The results of gut microbiota analysis showed that the intestinal microbiota composition of AM mice was altered. The ratio of Firmicutes/Bacteroidetes and the relative abundance of Lactobacillus in AM group increased compared with the control group. Sixty differential expressed metabolites were identified in intestinal metabolites, mainly involved in steroid hormone biosynthesis, cysteine and methionine metabolism, and alanine, aspartate, and glutamate metabolism. Further, correlation analysis verified that L-methionine and L-cystine were negatively correlated with Bacteroides and positively correlated with Desulfovibrio. The Pregnenolone, Androsterone glucuronide, and Testosterone glucuronide were negatively correlated with Unidentified_Ruminococcaceae and Alistipes, whereas they positively correlated with Bacteroides.<br><br>CONCLUSION: AM mice have a unique gut microbiome and intestinal metabolites.}, }
@article {pmid36920665, year = {2023}, author = {Costa, CJ and Cohen, MW and Goldberg, DC and Mellado, W and Willis, DE}, title = {Nicotinamide Riboside Improves Enteric Neuropathy in Streptozocin-Induced Diabetic Rats Through Myenteric Plexus Neuroprotection.}, journal = {Digestive diseases and sciences}, volume = {68}, number = {7}, pages = {2963-2974}, pmid = {36920665}, issn = {1573-2568}, mesh = {Humans ; Rats ; Animals ; Myenteric Plexus ; Streptozocin/adverse effects ; *Diabetes Mellitus, Experimental/complications/chemically induced ; Neuroprotection ; Niacinamide/adverse effects ; *Diabetic Neuropathies ; *Intestinal Pseudo-Obstruction ; }, abstract = {BACKGROUND: Diabetes Mellitus causes a systemic oxidative stress due in part to the hyperglycemia and the reactive oxygen species generated. Up to 75% of diabetic patients present with an autonomic neuropathy affecting the Enteric Nervous System. Deficits in the human population are chronic dysmotilities with either increased (i.e., constipation) or decreased (i.e., diarrhea) total gastrointestinal transit times. These are recapitulated in the streptozocin-induced diabetic rat, which is a model of Type I Diabetes Mellitus.<br><br>AIMS: Examine the effects that a precursor of nicotinamide adenosine dinucleotide (NAD), nicotinamide riboside (NR), had on the development of dysmotility in induced diabetic rats and if fecal microbiota transplant (FMT) could produce the same results.<br><br>MATERIALS AND METHODS: Utilizing a 6-week treatment paradigm, NR was administered intraperitoneally every 48&#xa0;h. Total gastrointestinal transit time was assessed weekly utilizing the carmine red method. Three weeks following hyperglycemic induction, FMT was performed between NR-treated animals and untreated animals.<br><br>SIGNIFICANT RESULTS: There is improvement in overall gastrointestinal transit time with the use of NR. 16S microbiome sequencing demonstrated decreased alpha and beta diversity in induced diabetic rats without change in animals receiving FMT. Improvements in myenteric plexus ganglia density in small and large intestines in diabetic animals treated with NR were seen.<br><br>CONCLUSIONS: NR treatment led to functional improvement in total gastrointestinal transit time in induced diabetic animals. This was associated with neuroprotection in the myenteric plexuses of both small and large intestines of induced diabetic rats. This represents an important first step in showing NR's benefit as a treatment for diabetic enteric neuropathy. Streptozocin-induced diabetic rats have improved transit times and increased myenteric plexus ganglia density when treated with intraperitoneal nicotinamide riboside.}, }
@article {pmid36919522, year = {2023}, author = {Merenstein, D and Pot, B and Leyer, G and Ouwehand, AC and Preidis, GA and Elkins, CA and Hill, C and Lewis, ZT and Shane, AL and Zmora, N and Petrova, MI and Collado, MC and Morelli, L and Montoya, GA and Szajewska, H and Tancredi, DJ and Sanders, ME}, title = {Emerging issues in probiotic safety: 2023 perspectives.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2185034}, pmid = {36919522}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents/adverse effects ; *Gastrointestinal Microbiome ; Prebiotics ; *Probiotics/adverse effects ; }, abstract = {Probiotics are used for both generally healthy consumers and in clinical settings. However, theoretical and proven adverse events from probiotic consumption exist. New probiotic strains and products, as well as expanding use of probiotics into vulnerable populations, warrants concise, and actionable recommendations on how to work toward their safe and effective use. The International Scientific Association for Probiotics and Prebiotics convened a meeting to discuss and produce evidence-based recommendations on potential acute and long-term risks, risks to vulnerable populations, the importance for probiotic product quality to match the needs of vulnerable populations, and the need for adverse event reporting related to probiotic use. The importance of whole genome sequencing, which enables determination of virulence, toxin, and antibiotic resistance genes, as well as clear assignment of species and strain identity, is emphasized. We present recommendations to guide the scientific and medical community on judging probiotic safety.}, }
@article {pmid36918627, year = {2023}, author = {Russell, MW and Muste, JC and Kuo, BL and Wu, AK and Singh, RP}, title = {Clinical trials targeting the gut-microbiome to effect ocular health: a systematic review.}, journal = {Eye (London, England)}, volume = {37}, number = {14}, pages = {2877-2885}, pmid = {36918627}, issn = {1476-5454}, mesh = {Humans ; *Gastrointestinal Microbiome ; Eye ; *Uveitis ; *Probiotics/therapeutic use ; Face ; }, abstract = {Clinical trials targeting the gut microbiome to mitigate ocular disease are now on the horizon. A review of clinical data thus far is essential to determine future directions in this novel promising field. This review examines recent clinical trials that support the plausibility of a gut-eye axis, and may form the basis of novel clinical interventions. PubMed was queried for English language clinical studies examining the relationships between gut microbiota and ocular pathology. 25 studies were extracted from 828 candidate publications, which suggest that gut imbalance is associated with ocular pathology. Of these, only four interventional studies exist which suggest probiotic supplementation or fecal microbiota transplant can reduce symptoms of chalazion or uveitis. The gut-eye axis appears to hold clinical relevance, but current data is limited in sample size and design. Further investigation via longitudinal clinical trials may be warranted.}, }
@article {pmid36918089, year = {2023}, author = {Kapoor, B and Gulati, M and Gupta, R and Singla, RK}, title = {Microbiota dysbiosis and myasthenia gravis: Do all roads lead to Rome?.}, journal = {Autoimmunity reviews}, volume = {22}, number = {5}, pages = {103313}, doi = {10.1016/j.autrev.2023.103313}, pmid = {36918089}, issn = {1873-0183}, mesh = {Humans ; Dysbiosis ; Rome ; *Probiotics/therapeutic use ; *Myasthenia Gravis/therapy ; Prebiotics ; *Gastrointestinal Microbiome ; }, abstract = {Dysregulated immune system with a failure to recognize self from non-self-antigens is one of the common pathogeneses seen in autoimmune diseases. The complex interplay of genetic and environmental factors is important for the occurrence and development of the disease. Among the environmental factors, disturbed gut microbiota (gut dysbiosis) has recently attracted particular attention, especially with advancement in human microbiome research. Although the alterations in microbiota have been seen in various autoimmune diseases, including those of nervous system, there is paucity of information on neuromuscular system diseases. Myasthenia gravis (MG) is one such rare autoimmune disease of neuromuscular junction, and is caused by generation of pathogenic autoantibodies to components of the postsynaptic muscle endplate. In the recent years, accumulating evidences have endorsed the key role of host microbiota, particularly those of gut, in the pathogenesis of MG. Differential microbiota composition, characterized by increased abundance of Fusobacteria, Bacteroidetes, and Proteobacteria, and decreased abundance of Actinobacteria and Firmicutes, has been seen in MG patients in comparison to healthy subjects. Disturbance of microbiota composition, particularly reduced ratio of Firmicutes/Bacteroidetes, alter the gut permeability, subsequently triggering the immunological response. Resultant reduction in levels of short chain fatty acids (SCFAs) is another factor contributing to the immunological response in MG patients. Modulation of gut microbiota via intervention of probiotics, prebiotics, synbiotics, postbiotics (metabiotics), and fecal microbiota transplantation (FMT) is considered to be the futuristic approach for the management of MG. This review summarizes the role of gut microbiota and their metabolites (postbiotics) in the progression of MG. Also, various bacteriotherapeutic approaches involving gut microbiota are discussed for the prevention of MG progression.}, }
@article {pmid36915683, year = {2023}, author = {Aoi, W and Inoue, R and Mizushima, K and Honda, A and Björnholm, M and Takagi, T and Naito, Y}, title = {Exercise-acclimated microbiota improves skeletal muscle metabolism via circulating bile acid deconjugation.}, journal = {iScience}, volume = {26}, number = {3}, pages = {106251}, pmid = {36915683}, issn = {2589-0042}, abstract = {Habitual exercise alters the intestinal microbiota composition, which may mediate its systemic benefits. We examined whether transplanting fecal microbiota from trained mice improved skeletal muscle metabolism in high-fat diet (HFD)-fed mice. Fecal samples from sedentary and exercise-trained mice were gavage-fed to germ-free mice. After receiving fecal samples from trained donor mice for 1 week, recipient mice had elevated levels of AMP-activated protein kinase (AMPK) and insulin growth factor-1 in skeletal muscle. In plasma, bile acid (BA) deconjugation was found to be promoted in recipients transplanted with feces from trained donor mice; free-form BAs also induced more AMPK signaling and glucose uptake than tauro-conjugated BAs. The transplantation of exercise-acclimated fecal microbiota improved glucose tolerance after 8 weeks of HFD administration. Intestinal microbiota may mediate exercise-induced metabolic improvements in mice by modifying circulating BAs. Our findings provide insights into the prevention and treatment of metabolic diseases.}, }
@article {pmid36913483, year = {2023}, author = {Rehman, A and Tyree, SM and Fehlbaum, S and DunnGalvin, G and Panagos, CG and Guy, B and Patel, S and Dinan, TG and Duttaroy, AK and Duss, R and Steinert, RE}, title = {A water-soluble tomato extract rich in secondary plant metabolites lowers trimethylamine-n-oxide and modulates gut microbiota: a randomized, double-blind, placebo-controlled cross-over study in overweight and obese adults.}, journal = {The Journal of nutrition}, volume = {153}, number = {1}, pages = {96-105}, doi = {10.1016/j.tjnut.2022.11.009}, pmid = {36913483}, issn = {1541-6100}, mesh = {Adult ; Humans ; Overweight ; *Gastrointestinal Microbiome ; *Solanum lycopersicum ; Cross-Over Studies ; Obesity ; Methylamines/metabolism ; Oxides ; }, abstract = {BACKGROUND: Natural products rich in polyphenols have been shown to lower plasma trimethylamine-n-oxide (TMAO) known for its proatherogenic effects by modulating the intestinal microbiota.<br><br>OBJECTIVES: We aimed to determine the impact of Fruitflow, a water-soluble tomato extract, on TMAO, fecal microbiota, and plasma and fecal metabolites.<br><br>METHODS: Overweight and obese adults (n = 22, BMI 28-35 kg/m[2]) were included in a double-blind, placebo-controlled, cross-over study receiving 2&#xd7;150 mg Fruitflow per day or placebo (maltodextrin) for 4 wk with a 6-week wash-out between interventions. Stool, blood, and urine samples were collected to assess changes in plasma TMAO (primary outcome) as well as fecal microbiota, fecal and plasma metabolites, and urine TMAO (secondary outcomes). In a subgroup (n = 9), postprandial TMAO was evaluated following a choline-rich breakfast (&#x223c;450 mg). Statistical methods included paired t-tests or Wilcoxon signed rank tests and permutational multivariate analysis of variance.<br><br>RESULTS: Fruitflow, but not placebo, reduced fasting levels of plasma (-1.5 &#x3bc;M, P &#x2264; 0.05) and urine (-19.1 &#x3bc;M, P &#x2264; 0.01) TMAO as well as plasma lipopolysaccharides (-5.3 ng/mL, P &#x2264; 0.05) from baseline to the end of intervention. However, these changes were significant only for urine TMAO levels when comparing between the groups (P &#x2264; 0.05). Changes in microbial beta, but not alpha, diversity paralleled this with a significant difference in Jaccard distance-based Principal Component (P &#x2264; 0.05) as well as decreases in Bacteroides, Ruminococccus, and Hungatella and increases in Alistipes when comparing between and within groups (P &#x2264; 0.05, respectively). There were no between-group differences in SCFAs and bile acids (BAs) in both faces and plasma but several changes within groups such as an increase in fecal cholic acid or plasma pyruvate with Fruitflow (P &#x2264; 0.05, respectively). An untargeted metabolomic analysis revealed TMAO as the most discriminant plasma metabolite between groups (P &#x2264; 0.05).<br><br>CONCLUSIONS: Our results support earlier findings that polyphenol-rich extracts can lower plasma TMAO in overweight and obese adults related to gut microbiota modulation. This trial was registered at clinicaltrials.gov as NCT04160481 (https://clinicaltrials.gov/ct2/show/NCT04160481?term= Fruitflow&amp;draw= 2&amp;rank= 2).}, }
@article {pmid36911747, year = {2023}, author = {Wang, L and Wei, Z and Pan, F and Song, C and Peng, L and Yang, Y and Huang, F}, title = {Case report: Fecal microbiota transplantation in refractory ankylosing spondylitis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1093233}, pmid = {36911747}, issn = {1664-3224}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Spondylitis, Ankylosing ; Feces ; *Gastrointestinal Microbiome ; *Microbiota ; *Colitis, Ulcerative/pathology ; }, abstract = {Ankylosing spondylitis (AS) is the prototype of a group of systemic inflammatory diseases referred to as spondyloarthritis. Comorbid inflammatory bowel disease and changed gut microbiota in AS have attracted attention to the influence of gut-joint axis and encouraged treating AS by targeting gut microbiota. Here we first reported a patient with refractory AS and comorbid ulcerative colitis (UC) who underwent three fecal microbiota transplantations (FMTs). Inadequate response to conventional treatments including tumor necrosis factor inhibitors impelled FMT as alternative therapy. Notable improvements in AS and UC accompanied with changed fecal microbiota were recorded at 1 week post-FMT1. Further recovery was found after the other two FMTs, and a roughly stable status was maintained in the follow-up period. More studies are needed to validate the effectiveness of FMT in AS and its mechanisms.}, }
@article {pmid36910213, year = {2023}, author = {Gholam-Mostafaei, FS and Azimirad, M and Naseri, K and Nabavi-Rad, A and Asadzadeh Aghdaei, H and Shahrokh, S and Ebrahimi Daryani, N and Yadegar, A and Zali, MR}, title = {Intestinal microbiota changes pre- and post-fecal microbiota transplantation for treatment of recurrent Clostridioides difficile infection among Iranian patients with concurrent inflammatory bowel disease.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1147945}, pmid = {36910213}, issn = {1664-302X}, abstract = {INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at a greater risk for the recurrence of Clostridioides difficile infection (rCDI) that is triggered by intestinal microbiota dysbiosis. Fecal microbiota transplantation (FMT) has emerged as a highly effective therapeutic option for this complication. However, little is known about the impact of FMT on intestinal microbiota alterations in rCDI patients suffering from IBD. In this study, we aimed to investigate post-FMT intestinal microbiota alterations in Iranian rCDI patients with underlying IBD.<br><br>METHODS: A total of 21 fecal samples were collected including 14 samples pre- and post-FMT and 7 samples from healthy donors. Microbial analysis was performed by quantitative real-time PCR (RT-qPCR) assay targeting the 16S rRNA gene. The pre-FMT profile and composition of the fecal microbiota were compared to the microbial changes of samples collected 28 days after FMT.<br><br>RESULTS AND DISCUSSION: Overall, the fecal microbiota profile of recipients was more similar to donor samples after the transplantation. We observed a significant increase in the relative abundance of Bacteroidetes post-FMT, compared to the pre-FMT microbial profile. Furthermore, there were remarkable differences between the microbial profile of pre-FMT, post-FMT, and healthy donor samples by PCoA analysis based on the ordination distance. This study demonstrates FMT as a safe and effective approach to restore the indigenous composition of the intestinal microbiota in rCDI patients and ultimately results in the treatment of concurrent IBD.}, }
@article {pmid36910163, year = {2023}, author = {van Lingen, EE and Baunwall, SSMD and Lieberknecht, SSC and Benech, NN and Ianiro, GG and Sokol, HH and Gasbarrini, AA and Cammarota, GG and Eriksen, MMK and van der Meulen-de Jong, AAE and Terveer, EEM and Verspaget, HHW and Vehreschild, MM and Hvas, CCL and Keller, JJJ}, title = {Short- and long-term follow-up after fecal microbiota transplantation as treatment for recurrent Clostridioides difficile infection in patients with inflammatory bowel disease.}, journal = {Therapeutic advances in gastroenterology}, volume = {16}, number = {}, pages = {17562848231156285}, pmid = {36910163}, issn = {1756-283X}, abstract = {BACKGROUND: Patients with inflammatory bowel disease (IBD) are at an increased risk of developing Clostridioides difficile infection (CDI). Treatment of CDI in patients with IBD is challenging due to higher failure rates and concomitant IBD activity.<br><br>OBJECTIVES: We performed a multicentre cohort study in patients with IBD who received fecal microbiota transplantation (FMT) for recurrent CDI (rCDI), to further investigate factors that influence the clinical outcome and course of both rCDI and IBD.<br><br>DESIGN: This is a multicentre cohort study conducted in five European FMT centres.<br><br>METHODS: Adult IBD patients treated with FMT for rCDI were studied. Cure was defined as clinical resolution of diarrhoea or diarrhoea with a negative C. difficile test. The definition of an IBD flare was record based. Long-term follow-up data were collected including new episodes of CDI, IBD flares, infections, hospital admissions, and death.<br><br>RESULTS: In total, 113 IBD patients underwent FMT because of rCDI. Mean age of the patients was 48&#x2009;years; 64% had ulcerative colitis. Concomitant rCDI was associated with an IBD flare in 54%, of whom 63% had received IBD remission-induction therapy prior to FMT. All FMT procedures were preceded by vancomycin treatment, 40% of patients received FMT via colonoscopy. CDI cure rate was 71%. Long-term follow-up data were available in 90 patients with a median follow-up of 784&#x2009;days (402-1251). IBD activity decreased in 39% of patients who had active IBD at baseline, whereas an IBD flare occurred in only 5%. During follow-up of up to 2&#x2009;years, 27% of the patients had infections, 39% were hospitalized, 5% underwent colectomy, and 10% died (median age of these latter patients: 72&#x2009;years).<br><br>CONCLUSION: FMT for rCDI in IBD patients is safe and effective, and IBD exacerbation after FMT is infrequent. Further studies should investigate the effects on IBD course following FMT.}, }
@article {pmid36909725, year = {2023}, author = {Zou, B and Liu, S and Li, X and He, J and Dong, C and Ruan, M and Huang, Z and Shu, S}, title = {Repeated and multiple fecal microbiota transplantations plus partial enteral nutrition as the first-line treatment in active pediatric Crohn's disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1083236}, pmid = {36909725}, issn = {2235-2988}, mesh = {Male ; Child ; Female ; Humans ; *Crohn Disease ; Fecal Microbiota Transplantation/methods ; Enteral Nutrition/methods ; Retrospective Studies ; Remission Induction ; Penicillin G ; Treatment Outcome ; }, abstract = {BACKGROUND: Most studies have reported fecal microbiota transplantation (FMT) as an effective secondary option for Crohn's disease (CD). However, there is little data on FMT as a first-line treatment for CD. In our study we explore the rates of clinical and endoscopic remission and mucosal healing after FMT plus partial enteral nutrition (PEN), as a first-line treatment for active CD in children.<br><br>METHODS: We retrospectively enrolled pediatric CD patients who underwent PEN or PEN plus FMT treatment at diagnosis from November 2016 to July 2019 at the Pediatric Department, Tongji Hospital. The two groups were defined as FMT group (repeated and multiple doses of FMT plus PEN) or PEN group (PEN alone). All the patients received PEN intervention. At baseline and week 8- 10, the FMT group was administered multiple doses of FMT to help induce and maintain remission. All patients were evaluated at week 8- 10 and 18-22 via clinical and relevant laboratory parameters and endoscopic results. The clinical and endoscopic remission and mucosal healing rates were compared between the two groups at different time points after the therapy.<br><br>RESULTS: Twenty-five newly diagnosed active CD patients were included in the study, containing 7 females and 18 males with a median age of 11. 1 &#xb1; 2.3 years. 13 and 12 patients were assigned to the PEN and FMT groups, respectively. At week 8-10, clinical remission was obtained in 83.3% and 53.8% of the FMT and PEN groups, respectively (p=0.202). The endoscopic remission rates were 72.7% for FMT and 25.0% for PEN (p=0.039), whereas the mucosal healing rates were 27.2% for FMT and 0% for PEN (p=0.093). At week 18-22, clinical remission was achieved in 72.7% and 20.0% of patients in the FMT and PEN groups, respectively (p=0.03). Theendoscopic remission rates were 66.6% and 12.5% in the FMT and PEN groups, respectively (p=0.05), whereas the mucosal healing rates were 55.5% and 0% in FMT and PEN groups, respectively (p=0.029).<br><br>CONCLUSION: This study demonstrate that FMT plus PEN can be used as a first-line treatment for active CD in children.}, }
@article {pmid36906253, year = {2023}, author = {Gao, T and Feng, M and Wang, Z and Cao, J and Chen, Y}, title = {Microbiota-gut-adipose axis: butyrate-mediated the improvement effect on inflammatory response and fatty acid oxidation dysregulation attenuates obesity in sleep-restricted mice.}, journal = {Microbes and infection}, volume = {25}, number = {6}, pages = {105125}, doi = {10.1016/j.micinf.2023.105125}, pmid = {36906253}, issn = {1769-714X}, mesh = {Animals ; Mice ; *Butyrates/pharmacology ; *Gastrointestinal Microbiome ; Lipopolysaccharides ; Dysbiosis/metabolism ; Glycogen Synthase Kinase 3 beta/pharmacology ; Obesity/metabolism ; Sleep ; }, abstract = {BACKGROUND: Insufficient sleep was considered as a substantial cause of obesity. The present study further explored the mechanism whereby sleep restriction (SR)-mediated intestinal dysbiosis induced metabolic disorder and ultimately lead to obesity in mice and the improvement effect of butyrate exerting on it.<br><br>METHODS: A continuous 3 months SR mouse model with or without butyrate supplementation and fecal microbiota transplantation to explore the key role of intestinal microbiota in butyrate improving inflammatory response in inguinal white adipose tissue (iWAT) and fatty acid oxidation dysfunction in brown adipose tissue (BAT), further ameliorating SR-induced obesity.<br><br>RESULTS: SR-mediated gut microbiota dysbiosis (down-regulation in butyrate level and up-regulation in LPS level) induced intestinal permeability increase and inflammatory response in iWAT and fatty acid oxidation dysfunction in BAT, ultimately resulting in obesity. Further, we demonstrated butyrate ameliorated gut microbiota homeostasis, suppressed inflammatory response via GPR43/LPS/TLR4/MyD88/GSK-3&#x3b2;/&#x3b2;-catenin loop in iWAT and restored fatty acid oxidation function via HDAC3/PPAR&#x3b1;/PGC-1&#x3b1;/UCP1/Calpain1 pathway in BAT, ultimately reversing SR-induced obesity.<br><br>CONCLUSIONS: We revealed that gut dysbiosis is a key factor for SR-induced obesity and provided a better understanding of the effects of butyrate. We further expected that reversing SR-induced obesity by improving microbiota-gut-adipose axis disorder could be a possible treatment for metabolic diseases.}, }
@article {pmid36905867, year = {2023}, author = {Zhang, CE and Yu, XH and Cui, YT and Wang, HJ and Chen, X and Ma, XJ and Li, H and Su, JR and Ma, ZJ and Huang, LQ}, title = {Shengjiang Xiexin Decoction ameliorates antibiotic-associated diarrhea by altering the gut microbiota and intestinal metabolic homeostasis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {113}, number = {}, pages = {154737}, doi = {10.1016/j.phymed.2023.154737}, pmid = {36905867}, issn = {1618-095X}, mesh = {Humans ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics/analysis ; Diarrhea/chemically induced/drug therapy ; Homeostasis ; Anti-Bacterial Agents/adverse effects ; }, abstract = {BACKGROUND: Antibiotic-associated diarrhea (AAD) has had a significant increase in the last years, with limited available effective therapies. Shengjiang Xiexin Decoction (SXD), a classic traditional Chinese medicine formula for treating diarrhea, is a promising alternative for reducing the incidence of AAD.<br><br>PURPOSE: This study aimed to explore the therapeutic effect of SXD on AAD and to investigate its potential therapeutic mechanism by integrated analysis of the gut microbiome and intestinal metabolic profile.<br><br>METHODS: 16S rRNA sequencing analysis of the gut microbiota and untargeted-metabolomics analysis of feces were performed. The mechanism was further explored by fecal microbiota transplantation (FMT).<br><br>RESULTS: SXD could effectively ameliorate AAD symptoms and restore intestinal barrier function. In addition, SXD could significantly improve the diversity of the gut microbiota and accelerate the recovery of the gut microbiota. At the genus level, SXD significantly increased the relative abundance of Bacteroides spp (p < 0.01) and decreased the relative abundance of Escherichia_Shigela spp (p < 0.001). Untargeted metabolomics showed that SXD significantly improved gut microbiota and host metabolic function, particularly bile acid metabolism and amino acid metabolism.<br><br>CONCLUSION: This study demonstrated that SXD could extensively modulate the gut microbiota and intestinal metabolic homeostasis to treat AAD.}, }
@article {pmid36904149, year = {2023}, author = {Yuan, C and Fan, J and Jiang, L and Ye, W and Chen, Z and Wu, W and Huang, Q and Qian, L}, title = {Integrated Analysis of Gut Microbiome and Liver Metabolome to Evaluate the Effects of Fecal Microbiota Transplantation on Lipopolysaccharide/D-galactosamine-Induced Acute Liver Injury in Mice.}, journal = {Nutrients}, volume = {15}, number = {5}, pages = {}, pmid = {36904149}, issn = {2072-6643}, mesh = {Mice ; Humans ; Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Lipopolysaccharides ; Galactosamine ; *Liver Failure, Acute/pathology ; Metabolome ; }, abstract = {Acute liver failure (ALF) refers to the occurrence of massive hepatocyte necrosis in a short time, with multiple complications, including inflammatory response, hepatic encephalopathy, and multiple organ failure. Additionally, effective therapies for ALF are lacking. There exists a relationship between the human intestinal microbiota and liver, so intestinal microbiota modulation may be a strategy for therapy of hepatic diseases. In previous studies, fecal microbiota transplantation (FMT) from fit donors has been used to modulate intestinal microbiota widely. Here, we established a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-gal) induced ALF to explore the preventive and therapeutic effects of FMT, and its mechanism of action. We found that FMT decreased hepatic aminotransferase activity and serum total bilirubin levels, and decreased hepatic pro-inflammatory cytokines in LPS/D-gal challenged mice (p < 0.05). Moreover, FMT gavage ameliorated LPS/D-gal induced liver apoptosis and markedly reduced cleaved caspase-3 levels, and improved histopathological features of the liver. FMT gavage also restored LPS/D-gal-evoked gut microbiota dysbiosis by modifying the colonic microbial composition, improving the abundance of unclassified_o_Bacteroidales (p < 0.001), norank_f_Muribaculaceae (p < 0.001), and Prevotellaceae_UCG-001 (p < 0.001), while reducing that of Lactobacillus (p < 0.05) and unclassified_f_Lachnospiraceae (p < 0.05). Metabolomics analysis revealed that FMT significantly altered LPS/D-gal induced disordered liver metabolites. Pearson's correlation revealed strong correlations between microbiota composition and liver metabolites. Our findings suggest that FMT ameliorate ALF by modulating gut microbiota and liver metabolism, and can used as a potential preventive and therapeutic strategy for ALF.}, }
@article {pmid36902512, year = {2023}, author = {Rodrigues, T and Rodrigues Fialho, S and Araújo, JR and Rocha, R and Moreira-Rosário, A}, title = {Procedures in Fecal Microbiota Transplantation for Treating Irritable Bowel Syndrome: Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {12}, number = {5}, pages = {}, pmid = {36902512}, issn = {2077-0383}, support = {RISE - LA/P/0053/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disease with no effective treatment. Altered microbiota composition seems implicated in disease etiology and therefore fecal microbial transplantation (FMT) has emerged as a possible treatment therapy. To clarify the clinical parameters impacting FMT efficacy, we conducted a systematic review with subgroup analysis.<br><br>METHODS: A literature search was performed identifying randomized controlled trials (RCTs) comparing FMT with placebo in IBS adult patients (8-week follow-up) with a reported improvement in global IBS symptoms.<br><br>RESULTS: Seven RCTs (489 participants) met the eligibility requirements. Although FMT seems not to be effective in global improvement of IBS symptoms, subgroup analysis shows that FMT through gastroscopy or nasojejunal tube are effective IBS treatments (RR 3.03; 95% CI 1.94-4.73; I[2] = 10%, p < 0.00001). When considering non-oral ingestion routes, IBS patients with constipation symptoms are more likely to benefit from FMT administration (p = 0.003 for the difference between IBS subtypes regarding constipation). Fresh fecal transplant and bowel preparation seem also to have impact on FMT efficacy (p = 0.03 and p = 0.01, respectively).<br><br>CONCLUSION: Our meta-analysis revealed a set of critical steps that could affect the efficacy of FMT as clinical procedure to treat IBS, nevertheless more RCTs are needed.}, }
@article {pmid36901792, year = {2023}, author = {Celiberto, F and Losurdo, G and Pricci, M and Girardi, B and Marotti, A and Di Leo, A and Ierardi, E}, title = {The State of the Art of Molecular Fecal Investigations for Helicobacter pylori (H. pylori) Antibiotic Resistances.}, journal = {International journal of molecular sciences}, volume = {24}, number = {5}, pages = {}, pmid = {36901792}, issn = {1422-0067}, mesh = {Humans ; Anti-Bacterial Agents/pharmacology ; *Helicobacter pylori ; Microbial Sensitivity Tests ; *Helicobacter Infections/drug therapy ; Drug Resistance, Microbial ; Drug Resistance, Bacterial ; }, abstract = {A new paradigm shift for the treatment of Helicobacter pylori (H. pylori) infection would be timely due to a progressive increase in antibiotic resistance. Such a shift in the perspective of the H. pylori approach should include the preliminary assessment of antibiotic resistance. However, the availability of sensitivity tests is not widespread and the guidelines have always indicated empirical treatments without taking into account the need to make sensitivity tests accessible, i.e., the necessary starting point for improving results in different geographical areas. Currently, the traditional tools for this purpose (culture) are based on performing an invasive investigation (endoscopy) and often involve technical difficulties; thus, they were only confined to the settings where multiple attempts at eradication have failed. In contrast, genotypic resistance testing of fecal samples using molecular biology methods is much less invasive and more acceptable to patients. The purpose of this review is to update the state of the art of molecular fecal susceptibility testing for the management of this infection and to extensively discuss the potential benefits of their large-scale deployment, i.e., novel pharmacological opportunities.}, }
@article {pmid36901656, year = {2023}, author = {Song, L}, title = {Toward Understanding Microbial Ecology to Restore a Degraded Ecosystem.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {5}, pages = {}, pmid = {36901656}, issn = {1660-4601}, mesh = {Humans ; *Ecosystem ; *Microbiota ; Fecal Microbiota Transplantation ; }, abstract = {The microbial community plays an important role in maintaining human health, addressing climate change, maintaining environmental quality, etc. High-throughput sequencing leads to the discovery and identification of more microbial community composition and function in diverse ecosystems. Microbiome therapeutics such as fecal microbiota transplantation for human health and bioaugmentation for activated sludge restoration have drawn great attention. However, microbiome therapeutics cannot secure the success of microbiome transplantation. This paper begins with a view on fecal microbiota transplantation and bioaugmentation and is followed by a parallel analysis of these two microbial therapeutic strategies. Accordingly, the microbial ecology mechanisms behind them were discussed. Finally, future research on microbiota transplantation was proposed. Successful application of both microbial therapeutics for human disease and bioremediation for contaminated environments relies on a better understanding of the microbial "entangled bank" and microbial ecology of these environments.}, }
@article {pmid36899725, year = {2023}, author = {Jia, X and He, Y and Kang, Z and Chen, S and Sun, W and Wang, J and Lai, S}, title = {Comparison of Fecal Microbiota Communities between Primiparous and Multiparous Cows during Non-Pregnancy and Pregnancy.}, journal = {Animals : an open access journal from MDPI}, volume = {13}, number = {5}, pages = {}, pmid = {36899725}, issn = {2076-2615}, support = {2021YFYZ0001//Science &amp; Technology Department of Sichuan Province/ ; SCCXTD-2022-13//Innovative Research Team of Beef Cattle in Sichuan Province/ ; }, abstract = {Imbalances in the gut microbiota composition may lead to several reproductive disorders and diseases during pregnancy. This study investigates the fecal microbiome composition between primiparous and multiparous cows during non-pregnancy and pregnancy to analyze the host-microbial balance at different stages. The fecal samples obtained from six cows before their first pregnancy (BG), six cows during their first pregnancy (FT), six open cows with more than three lactations (DCNP), and six pregnant cows with more than three lactations (DCP) were subjected to 16S rRNA sequencing, and a differential analysis of the fecal microbiota composition was performed. The three most abundant phyla in fecal microbiota were Firmicutes (48.68%), Bacteroidetes (34.45%), and Euryarchaeota (15.42%). There are 11 genera with more than 1.0% abundance at the genus level. Both alpha diversity and beta diversity showed significant differences among the four groups (p < 0.05). Further, primiparous women were associated with a profound alteration of the fecal microbiota. The most representative taxa included Rikenellaceae_RC9_gut_group, Prevotellaceae_UCG_003, Christensenellaceae_R_7_group, Ruminococcaceae UCG-005, Ruminococcaceae UCG-013, Ruminococcaceae UCG-014, Methanobrevibacter, and [Eubacterium] coprostanoligenes group, which were associated with energy metabolism and inflammation. The findings indicate that host-microbial interactions promote adaptation to pregnancy and will benefit the development of probiotics or fecal transplantation for treating dysbiosis and preventing disease development during pregnancy.}, }
@article {pmid36897813, year = {2023}, author = {Clottes, P and Benech, N and Dumot, C and Jarraud, S and Vidal, H and Mechtouff, L}, title = {Gut microbiota and stroke: New avenues to improve prevention and outcome.}, journal = {European journal of neurology}, volume = {30}, number = {11}, pages = {3595-3604}, doi = {10.1111/ene.15770}, pmid = {36897813}, issn = {1468-1331}, abstract = {Despite major recent therapeutic advances, stroke remains a leading cause of disability and death. Consequently, new therapeutic targets need to be found to improve stroke outcome. The deleterious role of gut microbiota alteration (often mentioned as "dysbiosis") on cardiovascular diseases, including stroke and its risk factors, has been increasingly recognized. Gut microbiota metabolites, such as trimethylamine-N-oxide, short chain fatty acids and tryptophan, play a key role. Evidence of a link between alteration of the gut microbiota and cardiovascular risk factors exists, with a possible causality link supported by several preclinical studies. Gut microbiota alteration also seems to be implicated at the acute phase of stroke, with observational studies showing more non-neurological complications, higher infarct size and worse clinical outcome in stroke patients with altered microbiota. Microbiota targeted strategies have been developed, including prebiotics/probiotics, fecal microbiota transplantation, short chain fatty acid and trimethylamine-N-oxide inhibitors. Research teams have been using different time windows and end-points for their studies, with various results. Considering the available evidence, it is believed that studies focusing on microbiota-targeted strategies in association with conventional stroke care should be conducted. Such strategies should be considered according to three therapeutic time windows: first, at the pre-stroke (primary prevention) or post-stroke (secondary prevention) phases, to enhance the control of cardiovascular risk factors; secondly, at the acute phase of stroke, to limit the infarct size and the systemic complications and enhance the overall clinical outcome; thirdly, at the subacute phase of stroke, to prevent stroke recurrence and promote neurological recovery.}, }
@article {pmid36897192, year = {2023}, author = {Zhang, B and Fan, X and Du, H and Zhao, M and Zhang, Z and Zhu, R and He, B and Zhang, Y and Li, X and Li, J and Gu, N}, title = {Foodborne Carbon Dot Exposure Induces Insulin Resistance through Gut Microbiota Dysbiosis and Damaged Intestinal Mucus Layer.}, journal = {ACS nano}, volume = {17}, number = {6}, pages = {6081-6094}, doi = {10.1021/acsnano.3c01005}, pmid = {36897192}, issn = {1936-086X}, mesh = {Animals ; Mice ; *Insulin Resistance ; *Gastrointestinal Microbiome ; Dysbiosis/chemically induced/metabolism ; RNA, Ribosomal, 16S ; Inflammation/metabolism ; Bacteria ; Mucus/metabolism ; Mice, Inbred C57BL ; Mammals ; }, abstract = {Foodborne carbon dots (CDs), an emerging food nanocontaminant, are an increasing risk factor for metabolic toxicity in mammals. Here, we report that chronic CD exposure induced glucose metabolism disorders via disruption of the gut-liver axis in mice. 16s rRNA analysis demonstrated that CD exposure decreased the abundance of beneficial bacteria (Bacteroides, Coprococcus, and S24-7) and increased the abundance of harmful bacteria (Proteobacteria, Oscillospira, Desulfovibrionaceae, and Ruminococcaceae), as well as increased the Firmicutes/Bacteroidetes ratio. Mechanistically, the increased pro-inflammatory bacteria release the endotoxin lipopolysaccharide, which induces an intestinal inflammation and disruption of the intestinal mucus layer, activating systemic inflammation and inducing hepatic insulin resistance in mice via the TLR4/NFκB/MAPK signaling pathway. Furthermore, these changes were almost completely reversed by probiotics. Fecal microbiota transplantation from CD-exposed mice induced glucose intolerance, damaged liver function, intestinal mucus layer injury, hepatic inflammation, and insulin resistance in the recipient mice. However, microbiota-depleted mice exposed to CDs had normal levels of these biomarkers consistent with microbiota-depleted control mice, which revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance. Together, our findings revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance and attempted to elucidate the specific underlying mechanism. Furthermore, we emphasized the importance of assessing the hazards associated with foodborne CDs.}, }
@article {pmid36896305, year = {2023}, author = {Zhao, JW and Chang, B and Sang, LX}, title = {Fecal microbiota transplantation as potential first-line treatment for patients with Clostridioides difficile infection and prior appendectomy.}, journal = {World journal of gastrointestinal surgery}, volume = {15}, number = {2}, pages = {303-306}, pmid = {36896305}, issn = {1948-9366}, abstract = {Clostridioides difficile infection (CDI) is a global health problem. The association of appendectomy on the severity and prognosis of CDI has been reported in many literatures, but there are still contradictions. In a retrospective study entitled "Patients with Closterium diffuse infection and prior appendectomy may be prone to word outcomes" published in World J Gastrointest Surg 2021, the author found that prior appendectomy affects the severity of CDI. Appendectomy may be a risk factor for increasing the severity of CDI. Therefore, it is necessary to seek alternative treatment for patients with prior appendectomy when they are more likely to have severe or fulminant CDI.}, }
@article {pmid36896026, year = {2023}, author = {Wang, J and Zhang, X and Li, M and Li, R and Zhao, M}, title = {Shifts in Intestinal Metabolic Profile Among Kidney Transplantation Recipients with Antibody-Mediated Rejection.}, journal = {Therapeutics and clinical risk management}, volume = {19}, number = {}, pages = {207-217}, pmid = {36896026}, issn = {1176-6336}, abstract = {BACKGROUND: Antibody-mediated rejection (AMR) is emerging as the main cause of graft loss after kidney transplantation. Our previous study revealed the gut microbiota alternation associated with AMR in kidney transplant recipients, which was predicted to affect the metabolism-related pathways.<br><br>METHODS: To further investigate the shifts in intestinal metabolic profile among kidney transplantation recipients with AMR, fecal samples from kidney transplant recipients and patients with end-stage renal disease (ESRD) were subjected to untargeted LC-MS-based metabolomics.<br><br>RESULTS: A total of 86 individuals were enrolled in this study, including 30 kidney transplantation recipients with AMR, 35 kidney transplant recipients with stable renal function (KT-SRF), and 21 participants with ESRD. Fecal metabolome in patients with ESRD and kidney transplantation recipients with KT-SRF were parallelly detected as controls. Our results demonstrated that intestinal metabolic profile of patients with AMR differed significantly from those with ESRD. A total of 172 and 25 differential metabolites were identified in the KT-AMR group, when compared with the ESRD group and the KT-SRF group, respectively, and 14 were common to the pairwise comparisons, some of which had good discriminative ability for AMR. KEGG pathway enrichment analysis demonstrated that the different metabolites between the KT-AMR and ESRD groups or between KT-AMR and KT-SRF groups were significantly enriched in 33 or 36 signaling pathways, respectively.<br><br>CONCLUSION: From the metabolic point of view, our findings may provide key clues for developing effective diagnostic biomarkers and therapeutic targets for AMR after kidney transplantation.}, }
@article {pmid36894930, year = {2023}, author = {Yang, J and Wang, L and Mei, M and Guo, J and Yang, X and Liu, S}, title = {Electroacupuncture repairs intestinal barrier by upregulating CB1 through gut microbiota in DSS-induced acute colitis.}, journal = {Chinese medicine}, volume = {18}, number = {1}, pages = {24}, pmid = {36894930}, issn = {1749-8546}, support = {81770536//National Natural Science Foundation of China/ ; 82270583//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: A few studies have reported that electroacupuncture (EA) can repair the intestinal barrier through unknown mechanisms. Cannabinoid receptor 1 (CB1) was shown to play an important role in the protection of the gut barrier in recent studies. Gut microbiota can influence the expression of CB1. In this study, we explored the effect of EA on the gut barrier in acute colitis and its mechanism.<br><br>METHODS: A dextran sulfate sodium (DSS)-induced acute colitis model, CB1 antagonist model and fecal microbiota transplantation (FMT) model were used in this study. The disease activity index (DAI) score, colon length, histological score, and inflammatory factors were detected to evaluate colonic inflammation. Methods for detecting intestinal barrier functions included the expression of tight junction proteins, intestinal permeability, and the number of goblet cells. Moreover, 16S rRNA sequencing was applied to analyze alterations in the gut microbiota. Western blotting and RT-PCR were performed to assess the levels of CB1 and autophagy-related proteins. Autophagosomes were observed by transmission electron microscopy.<br><br>RESULTS: EA reduced the DAI score, histological score, levels of inflammatory factors, and restored the colon length. Moreover, EA increased the expression of tight junction proteins and the number of goblet cells, and decreased intestinal permeability. In addition, EA remodeled the community structure of the gut microbiota, increased the expression of CB1, and enhanced the degree of autophagy. However, the therapeutic effects were reversed by CB1 antagonists. In addition, FMT in the EA group exhibited similar effects to EA and upregulated CB1.<br><br>CONCLUSIONS: We concluded that EA may protect intestinal barrier functions by increasing the expression of CB1 to enhance autophagy through gut microbiota in DSS-induced acute colitis.}, }
@article {pmid36893671, year = {2023}, author = {Yang, T and Guan, Q and Shi, JS and Xu, ZH and Geng, Y}, title = {Metformin alleviates liver fibrosis in mice by enriching Lactobacillus sp. MF-1 in the gut microbiota.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1869}, number = {5}, pages = {166664}, doi = {10.1016/j.bbadis.2023.166664}, pmid = {36893671}, issn = {1879-260X}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Lactobacillus ; *Metformin/pharmacology/therapeutic use ; Lipopolysaccharides/pharmacology ; RNA, Ribosomal, 16S/genetics ; Liver Cirrhosis/chemically induced/drug therapy ; }, abstract = {BACKGROUND: Liver fibrosis is associated with gut dysbiosis. Metformin administration has emerged as a promising method for the treatment of organ fibrosis. We aimed to investigate whether metformin ameliorates liver fibrosis by enhancing the gut microbiota in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and the underlying mechanism.<br><br>MATERIALS AND METHODS: A liver fibrosis mouse model was established, and the therapeutic effects of metformin were observed. We administered antibiotic treatment and performed fecal microbiota transplantation (FMT), and 16S rRNA-based microbiome analysis to evaluate the effects of the gut microbiome on metformin-treated liver fibrosis. We isolated the bacterial strain preferably enriched by metformin and assessed its antifibrotic effects.<br><br>RESULTS: Metformin treatment repaired the gut integrity of the CCl4-treated mice. It reduced the number of bacteria in colon tissues and reduced the portal vein lipopolysaccharide (LPS) levels. The FMT performed on the metformin-treated CCl4 mice alleviated their liver fibrosis and reduced their portal vein LPS levels. The markedly changed gut microbiota was screened out from the feces and named Lactobacillus sp. MF-1 (L. sp. MF-1). In the CCl4-treated mice, daily gavage of L. sp. MF-1 maintained gut integrity, inhibited bacterial translocation, and reduced liver fibrosis. Mechanistically, metformin or L. sp. MF-1 inhibited the apoptosis of intestinal epithelial cells and restored CD3[+] intestinal intraepithelial lymphocytes in the ileum and CD4[+]Foxp3[+] lamina propria lymphocytes in the colon.<br><br>CONCLUSIONS: Metformin and its enriched L. sp. MF-1 can reinforce the intestinal barrier to alleviate liver fibrosis by restoring immune function.}, }
@article {pmid36892328, year = {2023}, author = {Trinh, S and Keller, L and Herpertz-Dahlmann, B and Seitz, J}, title = {[Fecal Microbiota Transplants in the Context of (Child and Adolescent) Psychiatric Disorders].}, journal = {Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie}, volume = {51}, number = {6}, pages = {431-440}, doi = {10.1024/1422-4917/a000928}, pmid = {36892328}, issn = {1422-4917}, mesh = {Animals ; Humans ; Adolescent ; Child ; Fecal Microbiota Transplantation ; *Clostridioides difficile ; *Microbiota ; *Feeding and Eating Disorders ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Depressive Disorder, Major ; }, abstract = {Fecal Microbiota Transplants in the Context of (Child and Adolescent) Psychiatric Disorders Abstract: There has recently been a significant increase in interest in gut microbiota and its interaction with the brain (gut-brain axis). Not only are the findings of microbiome research interesting for basic scientists, they also offer relevant insights for clinical practice. A causal relationship between gut microbiome and various somatic diseases such as diabetes mellitus, inflammatory bowel diseases, and obesity as well as psychiatric diseases such as major depression, anxiety disorders, and eating disorders seems plausible. To study the causal relationship of intestinal bacteria with individual phenotypes, researchers apply so-called stool transplantations (fecal microbiota transplantations) in the preclinical context. For this purpose, they transfer microbiota samples from patients into laboratory animals to observe possible changes in phenotype. In the clinical context, fecal microbiota transplantation is already being used with therapeutic intentions for selected diseases, for example, recurrent infections with Clostridioides difficile or inflammatory bowel diseases; they have already become part of the official clinical guidelines for C. difficile. For many other diseases, however, including mental illnesses, the potential of using fecal transplantations for therapeutic purposes is still being explored. Previous findings suggest that the intestinal microbiome, particularly fecal microbiota transplantations, represent a promising starting point for new therapeutic approaches.}, }
@article {pmid36892039, year = {2023}, author = {He, J and Yang, M and Quan, X and Wen, J and Lan, Y and Yang, H and Zhao, G and Hou, Y and Lu, J and Xu, L and Wei, L}, title = {Microbial and metabolic features in renal transplant recipients with post-transplantation diabetes mellitus.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {30}, number = {6}, pages = {504-513}, doi = {10.1111/iju.15158}, pmid = {36892039}, issn = {1442-2042}, support = {2020JDJQ0066//Science and Technology Department of Sichuan Province/ ; 2020LZ03//China and Sichuan Provincial People's Hospital/ ; ZYGX2021YGLH210//China and University of Electronic Science and Technology of China &amp; Sichuan Provincial People's Hospital/ ; }, mesh = {Humans ; *Kidney Transplantation/adverse effects ; Risk Factors ; *Diabetes Mellitus/etiology ; Transplant Recipients ; }, abstract = {OBJECTIVE: Post-transplantation diabetes mellitus (PTDM) is a common complication in renal transplant recipients (RTRs). Gut microbiome plays important roles in a variety of chronic metabolic diseases, but its association with the occurrence and development of PTDM is still unknown. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of PTDM.<br><br>METHODS: A total of 100 RTRs fecal samples were collected in our study. Among them, 55 samples were submitted to Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of RTRs were comprehensively characterized.<br><br>RESULTS: The species Dialister invisus was significantly associated with fasting plasma glucose (FPG). The functions of tryptophan and phenylalanine biosynthesis were enhanced in RTRs with PTDM, while the functions of fructose and butyric acid metabolism were reduced. Fecal metabolome analysis indicated that RTRs with PTDM had unique metabolite distribution characteristics, and two differentially expressed specific metabolites were significantly correlated with FPG. The correlation analysis of gut microbiome and metabolites showed that gut microbiome had an obvious effect on the metabolic characteristics of RTRs with PTDM. Moreover, the relative abundance of microbial function is associated with the expression of several specific gut microbiome and metabolites.<br><br>CONCLUSIONS: Our study identified the characteristics of gut microbiome and fecal metabolites in RTRs with PTDM, and we also found two important metabolites and a bacterium were significantly associated with PTDM, which might be used as novel targets in the research field of PTDM.}, }
@article {pmid36891364, year = {2023}, author = {Gao, P and Liu, L and Zhang, Z and Xu, L and Wu, C and Fu, Q and Li, J and Wang, C}, title = {Abdominal catheter-induced intussusception following renal transplantation in two pediatric recipients: 2 cases report and literature review.}, journal = {Translational pediatrics}, volume = {12}, number = {2}, pages = {280-286}, pmid = {36891364}, issn = {2224-4344}, abstract = {BACKGROUND: Intussusception is a frequent abdominal emergency in the pediatric population when the proximal bowel invaginates into the distal bowel. However, catheter-induced intussusception has not previously been described in pediatric renal transplant recipients, and the risk factors need to be investigated.<br><br>CASE DESCRIPTION: We report 2 cases of post-transplant intussusception which were caused by abdominal catheters. Case 1 experienced ileocolonic intussusception 3 months after renal transplantation and presented with intermittent abdominal pain; the intussusception was successfully managed using air enema. However, this child experienced a total of 3 episodes of intussusception within 4 days, which discontinued only after removal of the peritoneal dialysis catheter. No further intussusception recurrence was observed and the patient's intermittent pain disappeared during the follow-up. Case 2 developed ileocolonic intussusception 2 days after renal transplantation and presented currant jelly stools. The intussusception was completely irreducible until the intraperitoneal drainage catheter was eliminated; the patient discharged normal feces during the following days. A search in the databases of PubMed, Web of Science, and Embase yielded 8 similar cases. Our 2 cases had a younger age at disease onset than those retrieved in the search, and abdominal catheter was revealed as a lead point. Possible leading points of the 8 previously reported cases included post-transplant lymphoproliferative disorder (PTLD), acute appendicitis, tuberculosis, lymphocele, and firm adhesions. We noted that our cases were managed successfully with nonoperative treatment, whereas the 8 reported cases underwent surgical intervention. All of the 10 cases of intussusception occurred after renal transplantation and showed that intussusception had been induced by a lead point.<br><br>CONCLUSIONS: Our 2 cases implied that abdominal catheter could be a lead point to induce intussusception, especially in pediatric recipients with abdominal disorder. This experience may be applicable to other surgeries involving indwelling abdominal catheters in children. Health practitioners should consider this pathologic lead point and avoid serious consequences when intussusception occurs.}, }
@article {pmid36891304, year = {2023}, author = {Liu, X and Tang, H and Zhou, Q and Zeng, Y and Lu, B and Chen, D and Li, Y and Qian, J and Chen, M and Zhao, J and Xu, Y and Wang, M and Tan, B}, title = {Gut microbiota composition in patients with advanced malignancies experiencing immune-related adverse events.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1109281}, pmid = {36891304}, issn = {1664-3224}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; *Carcinoma, Non-Small-Cell Lung ; *Lung Neoplasms ; *Colitis ; Fecal Microbiota Transplantation ; }, abstract = {INTRODUCTION: The gut microbiota is implicated in the occurrence and severity of immune-related adverse events (irAEs), but the role it plays as well as its causal relationship with irAEs has yet to be established.<br><br>METHODS: From May 2020 to August 2021, 93 fecal samples were prospectively collected from 37 patients with advanced thoracic cancers treated with anti-PD-1 therapy, and 61 samples were collected from 33 patients with various cancers developing different irAEs. 16S rDNA amplicon sequencing was performed. Antibiotic-treated mice underwent fecal microbiota transplantation (FMT) with samples from patients with and without colitic irAEs.<br><br>RESULTS: Microbiota composition was significantly different in patients with and without irAEs (P=0.001) and with and without colitic-type irAEs (P=0.003). Bifidobacterium, Faecalibacterium, and Agathobacter were less abundant and Erysipelatoclostridium more abundant in irAE patients, while Bacteroides and Bifidobacterium were less abundant and Enterococcus more abundant in colitis-type irAE patients. Major butyrate-producing bacteria were also less abundant in patients with irAEs than those without (P=0.007) and in colitic vs. non-colitic irAE patients (P=0.018). An irAE prediction model had an AUC of 86.4% in training and 91.7% in testing. Immune-related colitis was more common in colitic-irAE-FMT (3/9) than non-irAE-FMT mice (0/9).<br><br>CONCLUSIONS: The gut microbiota is important in dictating irAE occurrence and type, especially for immune-related colitis, possibly by modulating metabolic pathways.}, }
@article {pmid36890066, year = {2023}, author = {Wu, D and Zhang, C and Liu, Y and Yao, J and Yang, X and Wu, S and Du, J and Yang, X}, title = {Beyond faecal microbiota transplantation, the non-negligible role of faecal virome or bacteriophage transplantation.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {56}, number = {5}, pages = {893-908}, doi = {10.1016/j.jmii.2023.02.005}, pmid = {36890066}, issn = {1995-9133}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Bacteriophages ; Virome ; Feces/microbiology ; Forecasting ; Bacteria ; }, abstract = {Intestinal microbiota, which contains bacteria, archaea, fungi, protists, and viruses including bacteriophages, is symbiotic and evolves together with humans. The balanced intestinal microbiota plays indispensable roles in maintaining and regulating host metabolism and health. Dysbiosis has been associated with not only intestinal diseases but other diseases such as neurology disorders and cancers. Faecal microbiota transplantation (FMT) or faecal virome or bacteriophage transplantation (FVT or FBT), transfers faecal bacteria or viruses, with a focus on bacteriophage, from one healthy individual to another individual (normally unhealthy condition), and aims to restore the balanced gut microbiota and assist in subduing diseases. In this review, we summarized the applications of FMT and FVT in clinical settings, discussed the advantages and challenges of FMT and FVT currently and proposed several considerations prospectively. We further provided our understanding of why FMT and FVT have their limitations and raised the possible future development strategy of FMT and FVT.}, }
@article {pmid36889449, year = {2023}, author = {Kumei, S and Ishioh, M and Nozu, T and Okumura, T}, title = {Prostaglandin I2 suppresses the development of gut-brain axis disorder in irritable bowel syndrome in rats.}, journal = {Biochimica et biophysica acta. General subjects}, volume = {1867}, number = {5}, pages = {130344}, doi = {10.1016/j.bbagen.2023.130344}, pmid = {36889449}, issn = {1872-8006}, mesh = {Rats ; Animals ; *Irritable Bowel Syndrome/metabolism ; Brain-Gut Axis ; Epoprostenol ; Maternal Deprivation ; Feces ; }, abstract = {In this study, we attempted to clarify a role of prostaglandin (PG) I2 and its specific receptor, IP in the pathogenesis of irritable bowel syndrome (IBS) using a maternal separation (MS)-induced IBS model. Administration of beraprost (BPS), a specific IP agonist, improved visceral hypersensitivity and depressive state with decreased serum CRF level in the IBS rats. To clarify the mechanism of the effect of BPS, we performed serum metabolome analysis and 1-methylnicotinamide (1-MNA) was identified as a possible candidate for a clue metabolite of pathogenesis of IBS. The serum 1-MNA levels revealed inverse correlation to the level of visceral sensitivity, and positive correlation to a depression marker, immobilizing time. Administration of 1-MNA induced visceral hypersensitivity and depression with increased levels of serum CRF. Since fecal 1-MNA is known for a marker of dysbiosis, we examined the composition of fecal microbiota by T-RFLP analysis. The proportion of clostridium cluster XI, XIVa and XVIII was significantly changed in MS-induced IBS rats treated with BPS. Fecal microbiota transplant of BPS-treated rats improved visceral hypersensitivity and depression in IBS rats. These results suggest for the first time that PGI2-IP signaling plays an important role in IBS phenotypes such as visceral hypersensitivity and depressive state. BPS modified microbiota, thereby inhibition of 1-MNA-CRF pathway, followed by improvement of MS-induced IBS phenotype. These results suggest that the PGI2-IP signaling could be considered to be a therapeutic option for IBS.}, }
@article {pmid36883990, year = {2023}, author = {Wu, Y and Zheng, Y and Wang, X and Tang, P and Guo, W and Ma, H and Zhang, A and Li, D and Xie, Y and Wang, CZ and Yao, H and Wan, JY and Yuan, CS}, title = {Ginseng-Containing Sijunzi Decoction Ameliorates Ulcerative Colitis by Orchestrating Gut Homeostasis in Microbial Modulation and Intestinal Barrier Integrity.}, journal = {The American journal of Chinese medicine}, volume = {51}, number = {3}, pages = {677-699}, doi = {10.1142/S0192415X23500325}, pmid = {36883990}, issn = {1793-6853}, mesh = {Animals ; Mice ; *Colitis, Ulcerative/drug therapy ; *Panax ; Homeostasis ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Colitis ; Colon ; Dextran Sulfate ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Ulcerative colitis (UC) has become a global epidemic, and the lack of an effective cure highlights the necessity and urgency to explore novel therapies. Sijunzi Decoction (SJZD), a classical Chinese herbal formula, has been comprehensively applied and clinically proven effective in treating UC; however, the pharmacological mechanism behind its therapeutic benefits is largely obscure. Here, we find that SJZD can restore microbiota homeostasis and intestinal barrier integrity in DSS-induced colitis. SJZD significantly alleviated the colonic tissue damage and improved the goblet cell count, MUC2 secretion, and tight junction protein expressions, which indicated enhanced intestinal barrier integrity. SJZD remarkedly suppressed the abundance of phylum Proteobacteria and genus Escherichia-Shigella, which are typical features of microbial dysbiosis. Escherichia-Shigella was negatively correlated with body weight and colon length, and positively correlated with disease activity index and IL-1[Formula: see text]. Furthermore, through gut microbiota depletion, we confirmed that SJZD exerted anti-inflammatory activities in a gut microbiota-dependent manner, and fecal microbiota transplantation (FMT) validated the mediating role of gut microbiota in the SJZD treatment of UC. Through gut microbiota, SJZD modulates the biosynthesis of bile acids (BAs), especially tauroursodeoxycholic acid (TUDCA), which has been identified as the signature BA during SJZD treatment. Cumulatively, our findings disclose that SJZD attenuates UC via orchestrating gut homeostasis in microbial modulation and intestinal barrier integrity, thus offering a promising alternative approach to the clinical management of UC.}, }
@article {pmid36882658, year = {2023}, author = {Zhou, S and Cui, Y and Zhang, Y and Zhao, T and Cong, J}, title = {Fecal microbiota transplantation for induction of remission in Crohn's disease: a systematic review and meta-analysis.}, journal = {International journal of colorectal disease}, volume = {38}, number = {1}, pages = {62}, pmid = {36882658}, issn = {1432-1262}, support = {CNS-ZD2020-21//CNS-ZD Tizhi and Health Fund/ ; 2020BCA081-03//Key Research and Development Project of Hubei Province/ ; }, mesh = {Adult ; Humans ; *Crohn Disease/therapy ; Fecal Microbiota Transplantation/adverse effects ; Anti-Bacterial Agents ; Databases, Factual ; Remission Induction ; Randomized Controlled Trials as Topic ; }, abstract = {PURPOSE: Fecal microbiota transplantation (FMT) has been found to be a potential treatment for Crohn's disease (CD). We sought to perform a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD.<br><br>METHODS: Electronic databases were searched for studies until January 2023. Clinical remission was established as the primary outcome. The secondary outcome was clinical response, endoscopic remission, minor adverse events, serious adverse events, and changes in disease activity indices, biochemical indicators, and microbial diversities. Pooled effect sizes and 95% confidence intervals (CIs) were calculated under the random effects model.<br><br>RESULTS: Eleven cohort studies and one randomized controlled trial involving 228 patients were included. In a meta-analysis, the pooled proportion of adult patients with active CD that achieved clinical remission 2 to 4&#xa0;weeks after FMT was 57% (95% CI&#x2009;=&#x2009;49-64%) with a low risk of heterogeneity (I[2]&#x2009;=&#x2009;37%). Furthermore, our results showed that FMT significantly (standardized mean difference&#x2009;=&#x2009;-0.66; 95% CI&#x2009;=&#x2009;-1.12 to&#x2009;-0.20; I[2]&#x2009;=&#x2009;0) reduced Crohn's disease activity index scores 4 to 8&#xa0;weeks after FMT. Subgroup analyses showed no difference between FMT methodologies, except for pre-FMT treatment with antibiotics (P&#x2009;=&#x2009;0.02). Most adverse events were self-limiting and disappeared spontaneously within hours or days after FMT. Microbiota analysis showed an increased Shannon diversity and a shift toward donor-like microbiome after FMT.<br><br>CONCLUSION: FMT could be a promising therapy in the short-term treatment of active CD. More placebo-controlled randomized trials with a long-term follow-up treatment are necessary.<br><br>TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322694 No. CRD42022322694.}, }
@article {pmid36882216, year = {2023}, author = {Körner, E and Lorentz, A}, title = {Fecal microbiota transplantation in patients with irritable bowel syndrome: an overview of current studies.}, journal = {Journal of applied microbiology}, volume = {134}, number = {3}, pages = {}, doi = {10.1093/jambio/lxad044}, pmid = {36882216}, issn = {1365-2672}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Irritable Bowel Syndrome/therapy/complications/microbiology ; Quality of Life ; Feces/microbiology ; Intestines ; Treatment Outcome ; }, abstract = {As dysbiosis is a key factor associated with irritable bowel syndrome (IBS), modulation of the intestinal microbiota could improve IBS symptoms and quality of life. Fecal microbiota transplantation (FMT) could be one efficient way to restore bacterial composition in IBS patients. This review comprises 12 clinical trials published from 2017 to 2021. Inclusion criteria were the assessment of IBS symptoms using the IBS symptom severity score, quality of life measured by the lBS quality of life scale, and gut microbiota analysis. Improved symptoms were reported in all 12 studies, paralleling with an increased quality of life after FMT, but also partly after placebo treatment. The use of oral capsules showed that the placebo treatment can have similar or even stronger positive effects on IBS patients than FMT. Gastroscopic FMT appears to link modulation of the gut microbiome to significant symptom reduction in patients. The patient's microbiota profile shifted toward their respective donors. Symptom worsening or decreased quality of life after FMT was not reported. The results show that FMT could be a therapeutic approach in IBS patients. Further research is needed to investigate whether FMT has a more beneficial effect on IBS patient than placebo treatment with the patient's own stool, placebo capsules, or bowel cleansing. Moreover, optimal donor selection, frequency, dosage, and route of delivery still need to be defined.}, }
@article {pmid36881441, year = {2023}, author = {Daoust, L and Choi, BS and Agrinier, AL and Varin, TV and Ouellette, A and Mitchell, PL and Samson, N and Pilon, G and Levy, E and Desjardins, Y and Laplante, M and Anhê, FF and Houde, VP and Marette, A}, title = {Gnotobiotic mice housing conditions critically influence the phenotype associated with transfer of faecal microbiota in a context of obesity.}, journal = {Gut}, volume = {72}, number = {5}, pages = {896-905}, doi = {10.1136/gutjnl-2021-326475}, pmid = {36881441}, issn = {1468-3288}, support = {FDN-143247//CIHR/Canada ; }, mesh = {Animals ; Mice ; *Housing ; Housing Quality ; Obesity/metabolism ; *Microbiota ; Fecal Microbiota Transplantation ; Phenotype ; Diet, High-Fat/adverse effects ; Germ-Free Life ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVE: Faecal microbiota transplantation (FMT) in germ-free (GF) mice is a common approach to study the causal role of the gut microbiota in metabolic diseases. Lack of consideration of housing conditions post-FMT may contribute to study heterogeneity. We compared the impact of two housing strategies on the metabolic outcomes of GF mice colonised by gut microbiota from mice treated with a known gut modulator (cranberry proanthocyanidins (PAC)) or vehicle.<br><br>DESIGN: High-fat high-sucrose diet-fed GF mice underwent FMT-PAC colonisation in sterile individual positive flow ventilated cages under rigorous housing conditions and then maintained for 8 weeks either in the gnotobiotic-axenic sector or in the specific pathogen free (SPF) sector of the same animal facility.<br><br>RESULTS: Unexpectedly, 8 weeks after colonisation, we observed opposing liver phenotypes dependent on the housing environment of mice. Mice housed in the GF sector receiving the PAC gut microbiota showed a significant decrease in liver weight and hepatic triglyceride accumulation compared with control group. Conversely, exacerbated liver steatosis was observed in the FMT-PAC mice housed in the SPF sector. These phenotypic differences were associated with housing-specific profiles of colonising bacterial in the gut and of faecal metabolites.<br><br>CONCLUSION: These results suggest that the housing environment in which gnotobiotic mice are maintained post-FMT strongly influences gut microbiota composition and function and can lead to distinctive phenotypes in recipient mice. Better standardisation of FMT experiments is needed to ensure reproducible and translatable results.}, }
@article {pmid36880679, year = {2023}, author = {Kundu, S and Nayak, S and Rakshit, D and Singh, T and Shukla, R and Khatri, DK and Mishra, A}, title = {The microbiome-gut-brain axis in epilepsy: pharmacotherapeutic target from bench evidence for potential bedside applications.}, journal = {European journal of neurology}, volume = {30}, number = {11}, pages = {3557-3567}, doi = {10.1111/ene.15767}, pmid = {36880679}, issn = {1468-1331}, support = {SRG/2022/000961//Science and Engineering Research Board/ ; }, abstract = {The gut-brain axis augments the bidirectional communication between the gut and brain and modulates gut homeostasis and the central nervous system through the hypothalamic-pituitary-adrenal axis, enteroendocrine system, neuroendocrine system, inflammatory and immune pathways. Preclinical and clinical reports showed that gut dysbiosis might play a major regulatory role in neurological diseases such as epilepsy, Parkinson's, multiple sclerosis, and Alzheimer's disease. Epilepsy is a chronic neurological disease that causes recurrent and unprovoked seizures, and numerous risk factors are implicated in developing epilepsy. Advanced consideration of the gut-microbiota-brain axis can reduce ambiguity about epilepsy pathology, antiepileptic drugs, and effective therapeutic targets. Gut microbiota sequencing analysis reported that the level of Proteobacteria, Verrucomicrobia, Fusobacteria, and Firmicutes was increased and the level of Actinobacteria and Bacteroidetes was decreased in epilepsy patients. Clinical and preclinical studies also indicated that probiotics, ketogenic diet, faecal microbiota transplantation, and antibiotics can improve gut dysbiosis and alleviate seizure by enhancing the abundance of healthy biota. This study aims to give an overview of the connection between gut microbiota, and epilepsy, how gut microbiome changes may cause epilepsy, and whether gut microbiome restoration could be used as a treatment for epilepsy.}, }
@article {pmid36880221, year = {2023}, author = {Liu, J and Liu, H and Teng, Y and Qin, N and Ren, X and Xia, X}, title = {A high-sucrose diet causes microbiota composition shift and promotes the susceptibility of mice to Salmonella Typhimurium infection.}, journal = {Food &amp; function}, volume = {14}, number = {6}, pages = {2836-2846}, doi = {10.1039/d2fo03467k}, pmid = {36880221}, issn = {2042-650X}, mesh = {Mice ; Animals ; Salmonella typhimurium ; Sucrose/adverse effects ; Mice, Inbred C57BL ; *Salmonella Infections ; *Microbiota ; Diet, High-Fat/adverse effects ; }, abstract = {A westernized diet characterized by high fat and sugar is tightly associated with the development of metabolic diseases and inflammatory bowel disease. Although a high-fat diet has been extensively studied for its involvement in various diseases, fewer studies have examined the impact of a high-sugar diet on the development of certain diseases, particularly enteric infections. This study aimed to explore the effect of a high sucrose diet on Salmonella Typhimurium-induced infection. C57BL/6 mice received a normal diet (Control) or a high sucrose diet (HSD) for eight weeks and then were infected by Salmonella Typhimurium. The high-sugar diet profoundly altered the relative abundance of certain microbial taxa. Bacteroidetes and Verrucomicrobiota were more abundant in normal diet-fed mice than in HSD-fed mice. Moreover, short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) were significantly higher in mice from the control group than the HSD group. More S. Typhimurium counts in feces and other tissues were observed in HSD-fed mice after infection. Tight junction proteins and antimicrobial peptides were significantly decreased in HSD-fed mice. Fecal microbiota transplantation (FMT) demonstrated that mice that received normal fecal microbiota had lower Salmonella Typhimurium burdens compared with mice that received HSD fecal microbiota, indicating that the altered microbial communities are associated with the severity of infection. Together, these findings suggest that the excessive intake of sucrose disturbs intestinal homeostasis and predisposes mice to Salmonella-induced infection.}, }
@article {pmid36877601, year = {2024}, author = {Renteria, K and Nguyen, H and Koh, GY}, title = {The role of vitamin D in depression and anxiety disorders: a review of the literature.}, journal = {Nutritional neuroscience}, volume = {27}, number = {3}, pages = {262-270}, doi = {10.1080/1028415X.2023.2186318}, pmid = {36877601}, issn = {1476-8305}, mesh = {Animals ; Humans ; *Depression/microbiology ; *Vitamin D/therapeutic use ; Serotonin ; Anxiety Disorders/drug therapy ; Anxiety ; Vitamins ; }, abstract = {BACKGROUND: Prevalence of mental health disorders continue to increase worldwide. Over the past decades, suboptimal vitamin D (VD) levels and gut dysbiosis have been associated with neurological dysfunction and psychiatric disorders.<br><br>METHODS: In this review, we examined the available literature on VD and mental health disorders, particularly depression and anxiety, in both clinical and pre-clinical studies.<br><br>RESULTS: Our extensive review failed to find a link between VD deficiency, depression, and anxiety-related behavior in preclinical animal models. However, strong evidence suggests that VD supplementation may alleviate symptoms in chronically stressed rodents, with some promising evidence from clinical studies. Further, fecal microbiota transplantations suggest a potential role of gut microbiota in neuropsychiatric disorders, although the underlying mechanisms remain to be fully elucidated. It has been postulated that serotonin, primarily produced by gut bacteria, may be a crucial factor. Hence, whether VD has the ability to impact gut microbiota and modulate serotonin synthesis warrants further investigation.<br><br>CONCLUSIONS: Taken together, literature has suggested that VD may serve as a key regulator in the gut-brain axis to modulate gut microbiota and alleviate symptoms of depression and anxiety. The inconsistent results of VD supplementation in clinical studies, particularly among VD deficient participants, suggests that current intake recommendations may need to be re-evaluated for individuals at-risk (i.e. prior to diagnosis) of developing depression and/or anxiety.}, }
@article {pmid36876396, year = {2023}, author = {Ballif, A}, title = {[Not Available].}, journal = {Revue medicale suisse}, volume = {19}, number = {816}, pages = {434}, doi = {10.53738/REVMED.2023.19.816.434}, pmid = {36876396}, issn = {1660-9379}, mesh = {Humans ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; }, }
@article {pmid36876136, year = {2023}, author = {Takimoto, Y and Chu, PS and Nakamoto, N and Hagihara, Y and Mikami, Y and Miyamoto, K and Morikawa, R and Teratani, T and Taniki, N and Fujimori, S and Suzuki, T and Koda, Y and Ishihara, R and Ichikawa, M and Honda, A and Kanai, T}, title = {Myeloid TLR4 signaling promotes post-injury withdrawal resolution of murine liver fibrosis.}, journal = {iScience}, volume = {26}, number = {3}, pages = {106220}, pmid = {36876136}, issn = {2589-0042}, abstract = {The fate of resolution of liver fibrosis after withdrawal of liver injury is still incompletely elucidated. Toll-like receptor 4 (TLR4) in tissue fibroblasts is pro-fibrogenic. After withdrawal of liver injury, we unexpectedly observed a significant delay of fibrosis resolution as TLR4 signaling was pharmacologically inhibited in vivo in two murine models. Single-cell transcriptome analysis of hepatic CD11b[+] cells, main producers of matrix metalloproteinases (MMPs), revealed a prominent cluster of restorative Tlr4-expressing Ly6c2-low myeloid cells. Delayed resolution after gut sterilization suggested its microbiome-dependent nature. Enrichment of a metabolic pathway linking to a significant increase of bile salt hydrolase-possessing family Erysipelotrichaceae during resolution. Farnesoid X receptor-stimulating secondary bile acids including 7-oxo-lithocholic acids upregulated MMP12 and TLR4 in myeloid cells in vitro. Fecal material transplant in germ-free mice confirmed phenotypical correlations in vivo. These findings highlight a pro-fibrolytic role of myeloid TLR4 signaling after injury withdrawal and may provide targets for anti-fibrotic therapy.}, }
@article {pmid36875849, year = {2023}, author = {Maestri, M and Santopaolo, F and Pompili, M and Gasbarrini, A and Ponziani, FR}, title = {Gut microbiota modulation in patients with non-alcoholic fatty liver disease: Effects of current treatments and future strategies.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1110536}, pmid = {36875849}, issn = {2296-861X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is frequently associated with metabolic disorders, being highly prevalent in obese and diabetic patients. Many concomitant factors that promote systemic and liver inflammation are involved in NAFLD pathogenesis, with a growing body of evidence highlighting the key role of the gut microbiota. Indeed, the gut-liver axis has a strong impact in the promotion of NAFLD and in the progression of the wide spectrum of its manifestations, claiming efforts to find effective strategies for gut microbiota modulation. Diet is among the most powerful tools; Western diet negatively affects intestinal permeability and the gut microbiota composition and function, selecting pathobionts, whereas Mediterranean diet fosters health-promoting bacteria, with a favorable impact on lipid and glucose metabolism and liver inflammation. Antibiotics and probiotics have been used to improve NAFLD features, with mixed results. More interestingly, medications used to treat NAFLD-associated comorbidities may also modulate the gut microbiota. Drugs for the treatment of type 2 diabetes mellitus (T2DM), such as metformin, glucagon-like peptide-1 (GLP-1) agonists, and sodium-glucose cotransporter (SGLT) inhibitors, are not only effective in the regulation of glucose homeostasis, but also in the reduction of liver fat content and inflammation, and they are associated with a shift in the gut microbiota composition towards a healthy phenotype. Even bariatric surgery significantly changes the gut microbiota, mostly due to the modification of the gastrointestinal anatomy, with a parallel improvement in histological features of NAFLD. Other options with promising effects in reprogramming the gut-liver axis, such as fecal microbial transplantation (FMT) and next-generation probiotics deserve further investigation for future inclusion in the therapeutic armamentarium of NAFLD.}, }
@article {pmid36873657, year = {2023}, author = {Matošević, M and Kos, I and Davidović, M and Ban, M and Matković, H and Jakopčić, I and Vuković Brinar, I and Szilágyi, &#xc1; and Csuka, D and Sinkovits, G and Prohászka, Z and Vrljičak, K and Lamot, L}, title = {Hemolytic uremic syndrome in the setting of COVID-19 successfully treated with complement inhibition therapy: An instructive case report of a previously healthy toddler and review of literature.}, journal = {Frontiers in pediatrics}, volume = {11}, number = {}, pages = {1092860}, pmid = {36873657}, issn = {2296-2360}, abstract = {INTRODUCTION: As the global pandemic continues, new complications of COVID-19 in pediatric population have turned up, one of them being hemolytic uremic syndrome (HUS), a complement-mediated thrombotic microangiopathy (CM-TMA) characterized by triad of thrombocytopenia, microangiopathic hemolytic anemia and acute kidney injury (AKI). With both multisystem inflammatory syndrome in children (MIS-C) and HUS sharing complement dysregulation as one of the key factors, the aim of this case report is to highlight differences between these two conditions and also emphasize the importance of complement blockade as a treatment modality.<br><br>CASE REPORT: We describe a 21-month-old toddler who initially presented with fever and confirmed COVID-19. His condition quickly deteriorated and he developed oliguria, accompanied with diarrhea, vomiting and oral intake intolerance. HUS was suspected, supported with compelling laboratory findings, including decreased platelets count and C3 levels, elevated LDH, urea, serum creatinine and sC5b-9 and presence of schistocytes in peripheral blood, negative fecal Shiga toxin and normal ADAMTS13 metalloprotease activity. The patient was given C5 complement blocker Ravulizumab and started to display rapid improvement.<br><br>CONCLUSION: Although reports of HUS in the setting of COVID-19 continue to pour in, the questions of exact mechanism and similarities to MIS-C remain. Our case for the first time accentuates the use of complement blockade as a valuable treatment option in this scenario. We sincerely believe that reporting on HUS as a complication of COVID-19 in children will give rise to improved diagnosis and treatment, as well as better understanding of both of these intricating diseases.}, }
@article {pmid36867263, year = {2023}, author = {Brenig, A and Broekaert, I and Gerner, P and Posovszky, C and Hünseler, C and Joachim, A}, title = {Microbiome analysis and fecal microbiota transfer in pediatric gastroenterology - a structured online survey in German-speaking countries.}, journal = {International journal of colorectal disease}, volume = {38}, number = {1}, pages = {59}, pmid = {36867263}, issn = {1432-1262}, mesh = {Humans ; Child ; Fecal Microbiota Transplantation ; *Gastroenterology ; Donor Selection ; *Microbiota ; Nutritional Status ; }, abstract = {PURPOSE: To assess the current attitude and the status quo towards the use of microbiome analysis and fecal microbiota transfer (FMT) in pediatric patients in German-speaking pediatric gastroenterology centers.<br><br>METHODS: A structured online survey among all certified facilities of the German-speaking society of pediatric gastroenterology and nutrition (GPGE) was conducted from November 01, 2020, until March 30, 2021.<br><br>RESULTS: A total of 71 centers were included in the analysis. Twenty-two centers (31.0%) use diagnostic microbiome analysis, but only a few perform analysis frequently (2; 2.8%) or regularly (1; 1.4%). Eleven centers (15.5%) have performed FMT as a therapeutic approach. Most of these centers use individual in-house donor screening programs (61.5%). One-third (33.8%) of centers rate the therapeutic impact of FMT as high or moderate. More than two-thirds (69.0%) of all participants are willing to participate in studies assessing the therapeutic effect of FMT.<br><br>CONCLUSIONS: Guidelines for microbiome analyses and FMT in pediatric patients and clinical studies investigating their benefits are absolutely necessary to improve the patient-centered care in pediatric gastroenterology. The long-term and successful establishment of pediatric FMT centers with standardized procedures for patient selection, donor screening, application route, volume, and frequency of use is highly required to obtain a safe therapy.}, }
@article {pmid36864569, year = {2023}, author = {Liu, Y and Ji, X and Huang, Y and Li, Q and Ding, X and Wang, Y and Zhang, S and Wen, Q and Cui, B and Lu, X and Zhang, F}, title = {Older patients benefit more from sequential courses of washed microbiota transplantation than younger population with ulcerative colitis.}, journal = {Scandinavian journal of gastroenterology}, volume = {58}, number = {8}, pages = {890-899}, doi = {10.1080/00365521.2023.2185476}, pmid = {36864569}, issn = {1502-7708}, mesh = {Humans ; *Colitis, Ulcerative/therapy/etiology ; Retrospective Studies ; Prospective Studies ; Fecal Microbiota Transplantation/methods ; Treatment Outcome ; *Microbiota ; Feces ; }, abstract = {OBJECTIVES: The short-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) has increasingly been evaluated. However, few studies have examined the long-term efficacy and its predictors. This study aimed to assess the clinical factors affecting the long-term efficacy of FMT for patients with UC.<br><br>METHODS: This is a retrospective analysis of a prospective trial (NCT01790061) for patients with UC undergoing washed microbiota transplantation (WMT), which is the improved methodology of FMT. The long-term clinical efficacy of WMT and the factors affecting efficacy were analyzed.<br><br>RESULTS: A total of 259 patients were included for analysis. Of 70.7% (183/259) of patients achieved a clinical response at 1 month after WMT and 29.7% (77/259) achieved steroid-free clinical remission 6 months after WMT. Total 44 patients maintained a clinical response for &#x2265;24&#x2009;months, and 33 (17.1%, 33/193) achieved steroid-free clinical remission for &#x2265;24&#x2009;months with WMT monotherapy. Patients with age at UC onset of &#x2265;60&#x2009;years, mild disease severity and undergoing &#x2265;2 courses of WMT during the response within 6 months were more likely to achieve steroid-free clinical remission 6 months after WMT. Besides, independent factors associated with the long-term response of WMT for UC were age at onset of &#x2265;60&#x2009;years and &#x2265;2 courses of WMT during the response.<br><br>CONCLUSIONS: This study indicated WMT could induce short-term steroid-free clinical remission and maintain long-term response in UC, especially for older patients and patients undergoing sequential courses.}, }
@article {pmid36863483, year = {2023}, author = {Spreafico, A and Heirali, AA and Araujo, DV and Tan, TJ and Oliva, M and Schneeberger, PHH and Chen, B and Wong, MK and Stayner, LA and Hansen, AR and Saibil, SD and Wang, BX and Cochrane, K and Sherriff, K and Allen-Vercoe, E and Xu, W and Siu, LL and Coburn, B}, title = {First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial).}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {34}, number = {6}, pages = {520-530}, doi = {10.1016/j.annonc.2023.02.011}, pmid = {36863483}, issn = {1569-8041}, mesh = {Animals ; Humans ; *Immune Checkpoint Inhibitors/therapeutic use ; Ecosystem ; Treatment Outcome ; Fecal Microbiota Transplantation/methods ; *Melanoma/drug therapy ; }, abstract = {BACKGROUND: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use.<br><br>PATIENTS AND METHODS: We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors.<br><br>RESULTS: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes; however, differences in MET4 species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids.<br><br>CONCLUSIONS: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer.}, }
@article {pmid36863429, year = {2023}, author = {Lian, Z and Xu, Y and Wang, C and Chen, Y and Yuan, L and Liu, Z and Liu, Y and He, P and Cai, Z and Zhao, J}, title = {Gut microbiota-derived melatonin from Puerariae Lobatae Radix-resistant starch supplementation attenuates ischemic stroke injury via a positive microbial co-occurrence pattern.}, journal = {Pharmacological research}, volume = {190}, number = {}, pages = {106714}, doi = {10.1016/j.phrs.2023.106714}, pmid = {36863429}, issn = {1096-1186}, mesh = {Animals ; Rats ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; *Ischemic Stroke/drug therapy ; *Melatonin/pharmacology/therapeutic use ; Prebiotics ; *Pueraria ; Resistant Starch ; *Central Nervous System Depressants/pharmacology/therapeutic use ; }, abstract = {Ischemic stroke is closely associated with gut microbiota dysbiosis and intestinal barrier dysfunction. Prebiotic intervention could modulate the intestinal microbiota, thus considered a practical strategy for neurological disorders. Puerariae Lobatae Radix-resistant starch (PLR-RS) is a potential novel prebiotic; however, its role in ischemic stroke remains unknown. This study aimed to clarify the effects and underlying mechanisms of PLR-RS in ischemic stroke. Middle cerebral artery occlusion surgery was performed to establish a model of ischemic stroke in rats. After gavage for 14 days, PLR-RS attenuated ischemic stroke-induced brain impairment and gut barrier dysfunction. Moreover, PLR-RS rescued gut microbiota dysbiosis and enriched Akkermansia and Bifidobacterium. We transplanted the fecal microbiota from PLR-RS-treated rats into rats with ischemic stroke and found that the brain and colon damage were also ameliorated. Notably, we found that PLR-RS promoted the gut microbiota to produce a higher level of melatonin. Intriguingly, exogenous gavage of melatonin attenuated ischemic stroke injury. In particular, melatonin attenuated brain impairment via a positive co-occurrence pattern in the intestinal microecology. Specific beneficial bacteria served as leaders or keystone species to promoted gut homeostasis, such as Enterobacter, Bacteroidales_S24-7_group, Prevotella_9, Ruminococcaceae and Lachnospiraceae. Thus, this new underlying mechanism could explain that the therapeutic efficacy of PLR-RS on ischemic stroke at least partly attributed to gut microbiota-derived melatonin. In summary, improving intestinal microecology by prebiotic intervention and melatonin supplementation in the gut were found to be effective therapies for ischemic stroke.}, }
@article {pmid36863036, year = {2023}, author = {Grover, S}, title = {Continuing Medical Education Questions: March 2023.}, journal = {The American journal of gastroenterology}, volume = {118}, number = {3}, pages = {404}, doi = {10.14309/ajg.0000000000002199}, pmid = {36863036}, issn = {1572-0241}, mesh = {Humans ; *Education, Medical, Continuing ; *Fecal Microbiota Transplantation ; }, abstract = {Article Title: Fecal Microbiota Transplantation Across the Lifespan- Balancing Efficacy, Safety, and Innovation.}, }
@article {pmid36859447, year = {2023}, author = {Zhang, Y and Peng, Y and Xia, X}, title = {Autoimmune diseases and gut microbiota: a bibliometric and visual analysis from 2004 to 2022.}, journal = {Clinical and experimental medicine}, volume = {23}, number = {6}, pages = {2813-2827}, pmid = {36859447}, issn = {1591-9528}, support = {pdjh2023b0107//Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province/ ; 202212121008//National College Students Innovation and Entrepreneurship Training Program/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; *Autoimmune Diseases/therapy ; *Arthritis, Rheumatoid ; Bibliometrics ; }, abstract = {Many studies have shown that gut microbiota is closely related to autoimmune diseases (ADs). Studies on gut microbiota and ADs have also increased significantly, but no bibliometric analysis has summarized the association between gut microbiota and ADs. This study aimed to conduct a bibliometric and visual analysis of published studies on gut microbiota and ADs. Based on the Web of Science Core Collection SCI-expanded database, we utilize Excel 2019 and visualization analysis tools VOSviewer and co-occurrence13.2 (COOC13.2) for analysis. A total of 2516 related kinds of literature were included, and the number of papers presented an overall increasing trend. The country/region with the most publications is the USA, the institution is the Harvard Medical School, and the author is Mikael Knip from the USA. Hot research areas include intestinal regulation (such as dysbiosis, short chain fatty acids, and probiotics), multisystem ADs (such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease), and immune-related cells (such as T cells, and dendritic cells). Psoriasis, dysbiosis, autoimmune liver disease, and fecal microbiota transplantation may be the future research direction. Our research results can help researchers grasp the current status of ADs and gut microbiota research and find new research directions in the future.}, }
@article {pmid36858183, year = {2023}, author = {Guo, P and Yang, X and Guo, X and Yang, H and Pan, J and Li, Y}, title = {Dietary fish oil improves autistic behaviors and gut homeostasis by altering the gut microbial composition in a mouse model of fragile X syndrome.}, journal = {Brain, behavior, and immunity}, volume = {110}, number = {}, pages = {140-151}, doi = {10.1016/j.bbi.2023.02.019}, pmid = {36858183}, issn = {1090-2139}, mesh = {Animals ; Mice ; *Fragile X Syndrome/genetics/metabolism ; *Autistic Disorder ; *Gastrointestinal Microbiome ; Dysbiosis ; Disease Models, Animal ; Mice, Knockout ; Fish Oils/pharmacology ; Fragile X Mental Retardation Protein/genetics ; }, abstract = {Fragile X syndrome (FXS) is the most common inherited intellectual disability, caused by a lack of the fragile X mental retardation protein (FMRP). Individuals with neurodevelopmental disorders frequently experience gastrointestinal problems that are primarily linked to gut microbial dysbiosis, inflammation, and increased intestinal permeability. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are non-pharmacological agents that exert potential therapeutic effects against neurological disorders. However, it is unclear whether omega-3 PUFAs improve autistic behaviors in fragile X syndrome (FXS) by altering the gut microbial composition. Here, we describe gastrointestinal problems in Fmr1 knockout (KO) mice. FMRP deficiency causes intestinal homeostasis dysfunction in mice. Fish oil (FO) as a source of omega-3 PUFAs reduces intestinal inflammation but increases the mRNA and protein levels of TJP3 in the colon of juvenile Fmr1 KO mice. Fecal microbiota transplantation from FO-fed Fmr1 KO mice increased the gut abundance of Akkermansia and Gordonibacter in recipient Fmr1 KO mice and improved gut homeostasis and autistic behaviors. Our findings demonstrate that omega-3 PUFAs improve autistic behaviors and gut homeostasis in FMRP-deficient mice by suppressing gut microbiota dysbiosis, thereby presenting a novel therapeutic approach for juvenile FXS treatment.}, }
@article {pmid36858036, year = {2023}, author = {Saleh, A and Parsa, S and Garza, M and Quigley, EMM and Abraham, BP}, title = {The Role of Fecal Microbiota Transplantation in the Induction of Remission in Ulcerative Colitis.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {41}, number = {4}, pages = {656-665}, doi = {10.1159/000529591}, pmid = {36858036}, issn = {1421-9875}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy ; Feces/microbiology ; *Inflammatory Bowel Diseases ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: Considerable research supports an important role for the microbiome and/or microbiome-host immune system interactions in the pathogenesis of inflammatory bowel disease (IBD). Consequently, microbiota-modulating interventions, such as fecal microbiota transplantation (FMT), have attracted interest in the management of IBD, including ulcerative colitis (UC).<br><br>SUMMARY: While the clinical response to FMT in UC has varied between different studies, results to date may offer guidance toward optimal use of FMT. Thus, increased microbiome biodiversity, the presence of short-chain fatty acid-producing bacteria, Clostridium clusters IV and XIVa, Odoribacter splanchnicus, and reduced levels of Caudovirales bacteriophages have been identified as characteristics of the donor microbiome that predict a positive response. However, inconsistency in FMT protocol between studies confounds their interpretation, so it is currently difficult to predict response and premature to recommend FMT, in general, as a treatment for UC. Additional randomized controlled trials designed based on previous findings and employing a standardized protocol are needed to define the role of FMT in the management of UC.<br><br>KEY MESSAGES: There is a well-developed rationale for the use of microbiome-modulating interventions in UC. Despite variations in study protocol and limitations in study design that confound their interpretation, FMT seems to benefit patients with UC, overall. Available data identify factors predicting FMT response and should lead to the development of optimal FMT study protocols.}, }
@article {pmid36848791, year = {2023}, author = {Tong, M and Yang, X and Liu, H and Ge, H and Huang, G and Kang, X and Yang, H and Liu, Q and Ren, P and Kuang, X and Yan, H and Shen, X and Qiao, Y and Kang, Y and Li, L and Yang, Y and Fan, W}, title = {The Trichinella spiralis-derived antigens alleviate HFD-induced obesity and inflammation in mice.}, journal = {International immunopharmacology}, volume = {117}, number = {}, pages = {109924}, doi = {10.1016/j.intimp.2023.109924}, pmid = {36848791}, issn = {1878-1705}, mesh = {Animals ; Mice ; *Diet, High-Fat/adverse effects ; *Trichinella spiralis ; Dysbiosis/metabolism ; Mice, Inbred C57BL ; Obesity/metabolism ; Inflammation/drug therapy/complications ; Cytokines/therapeutic use ; }, abstract = {Obesity, an increasingly prevalent disease worldwide, is accompanied by chronic inflammation and intestinal dysbiosis. Helminth infections have been increasingly proved to exhibit a protective role in several inflammation-associated diseases. Considering the side effects of live parasite therapy, efforts have been made to develop helminth-derived antigens as promising candidates with fewer adverse effects. This study aimed to evaluate the effect and mechanisms of TsAg (T. spiralis-derived antigens) on obesity and the associated inflammation in high-fat diet (HFD)-fed mice. C57BL/6J mice were fed a normal diet or HFD with or without TsAg treatment. The results reported that TsAg treatment alleviated body weight gain and chronic inflammation induced by HFD. In the adipose tissue, TsAg treatment prevented macrophage infiltration, reduced the expression of Th1-type (IFN-γ) and Th17-type (IL-17A) cytokines while upregulating the production of Th2-type (IL-4) cytokines. Furthermore, TsAg treatment enhanced brown adipose tissue activation and energy and lipid metabolism and reduced intestinal dysbiosis, intestinal barrier permeability and LPS/TLR4 axis inflammation. Finally, the protective role of TsAg against obesity was transmissible via the fecal microbiota transplantation approach. For the first time, our findings showed that TsAg alleviated HFD-induced obesity and inflammation via modulation of the gut microbiota and balancing the immune disorders, suggesting that TsAg might be a safer promising therapeutic strategy for obesity.}, }
@article {pmid36847237, year = {2023}, author = {}, title = {Fecal microbiota, live-jslm.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {80}, number = {9}, pages = {e79-e80}, doi = {10.1093/ajhp/zxad032}, pmid = {36847237}, issn = {1535-2900}, mesh = {Humans ; Feces ; *Fecal Microbiota Transplantation ; *Microbiota ; }, }
@article {pmid36845793, year = {2023}, author = {Erguibi, D and Kamal, K and Eddaoudi, Y and Hajri, A and Boufettal, R and Rifki El Jai, S and Chehab, F}, title = {Parietal mass caused by a fish bone: case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {2}, pages = {299-301}, pmid = {36845793}, issn = {2049-0801}, abstract = {UNLABELLED: It is a great challenge to distinguish the parietal inflammation, centered on the foreign body that pierced the digestive tract and remained in the wall before surgery, because of its atypical clinical nature. Ingestion of foreign bodies is not uncommon. Fish bones are particularly notorious culprits; however, most will pass through the gastrointestinal tract uneventfully.<br><br>PATIENTS AND METHODS: The authors report a case of a patient who presented with periumbilical abdominal pain and a computed tomography (CT) scan that revealed the presence of periumbilical fat infiltration on a foreign body admitted on the Department of Digestive Cancer Surgery and Liver Transplantation, Casablanca, Morocco. An exploratory laparotomy revealed a parietal mass centered by a fish bone.<br><br>RESULTS: Accidental ingestion of foreign bodies is common in clinical practice. However, perforation of the intestine by a foreign body is less common because the majority of foreign bodies pass without incident into the feces and only 1% of them (the sharpest and most elongated objects) will perforate the gastrointestinal tract, usually at the level of the ileum.CT, especially multidetector CT, is considered the method of choice for preoperative diagnoses of ingested foreign bodies and their complications due to its high-quality multiplanar capabilities and high resolution.Foreign body ingestion usually goes unnoticed, but the complications of this incident can be severe.<br><br>CONCLUSION: This case report highlights the fact that intestinal perforation caused by an ingested foreign body is a difficult diagnosis that should always be suspected in an attack of abdominal pain. Frequently, the clinical diagnosis is difficult, and recourse to imaging is sometimes necessary. Most of the time, the treatment is only surgical.}, }
@article {pmid36844730, year = {2023}, author = {Hatahet, J and Cook, TM and Bonomo, RR and Elshareif, N and Gavini, CK and White, CR and Jesse, J and Mansuy-Aubert, V and Aubert, G}, title = {Fecal microbiome transplantation and tributyrin improves early cardiac dysfunction and modifies the BCAA metabolic pathway in a diet induced pre-HFpEF mouse model.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1105581}, pmid = {36844730}, issn = {2297-055X}, support = {K08 HL145136/HL/NHLBI NIH HHS/United States ; }, abstract = {More than 50% of patients with heart failure present with heart failure with preserved ejection fraction (HFpEF), and 80% of them are overweight or obese. In this study we developed an obesity associated pre-HFpEF mouse model and showed an improvement in both systolic and diastolic early dysfunction following fecal microbiome transplant (FMT). Our study suggests that the gut microbiome-derived short-chain fatty acid butyrate plays a significant role in this improvement. Cardiac RNAseq analysis showed butyrate to significantly upregulate ppm1k gene that encodes protein phosphatase 2Cm (PP2Cm) which dephosphorylates and activates branched-chain α-keto acid dehydrogenase (BCKDH) enzyme, and in turn increases the catabolism of branched chain amino acids (BCAAs). Following both FMT and butyrate treatment, the level of inactive p-BCKDH in the heart was reduced. These findings show that gut microbiome modulation can alleviate early cardiac mechanics dysfunction seen in the development of obesity associated HFpEF.}, }
@article {pmid36844713, year = {2023}, author = {Halper-Stromberg, A and Dalal, SR}, title = {The Role of the Microbiome in the Etiology of Inflammatory Bowel Diseases.}, journal = {Clinics in colon and rectal surgery}, volume = {36}, number = {2}, pages = {120-126}, pmid = {36844713}, issn = {1531-0043}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; }, abstract = {Inflammatory bowel diseases (IBDs) result from dysregulated immune responses to environmental and microbial triggers in genetically susceptible hosts. Many clinical observations and animal studies support the role of the microbiome in the pathogenesis of IBD. Restoration of the fecal stream leads to postoperative Crohn's recurrence, while diversion can treat active inflammation. Antibiotics can be effective in prevention of postoperative Crohn's recurrence and in pouch inflammation. Several gene mutations associated with Crohn's risk lead to functional changes in microbial sensing and handling. However, the evidence linking the microbiome to the IBD is largely correlative, given the difficulty in studying the microbiome before disease occurs. Attempts to modify the microbial triggers of inflammation have had modest success to date. Exclusive enteral nutrition can treat Crohn's inflammation though no whole food diet to date has been shown to treat inflammation. Manipulation of the microbiome through fecal microbiota transplant and probiotics have had limited success. Further focus on early changes in the microbiome and functional consequences of microbial changes through the study of metabolomics are needed to help advance the field.}, }
@article {pmid36844712, year = {2023}, author = {Paine, H and Jones, F and Kinross, J}, title = {Preparing the Bowel (Microbiome) for Surgery: Surgical Bioresilience.}, journal = {Clinics in colon and rectal surgery}, volume = {36}, number = {2}, pages = {138-145}, pmid = {36844712}, issn = {1531-0043}, abstract = {The preparation of the bowel for radical surgery is a corner stone of elective colorectal practice. The evidence for this intervention is of variable quality and it is often contradictory, yet there is now a global move toward the adoption of oral antibiotic therapy for the reduction of perioperative infective complications, such as surgical site infections. The gut microbiome is a critical mediator of the systemic inflammatory response to surgical injury, wound healing, and perioperative gut function. The loss of critical microbial symbiotic functions caused by bowel preparation and surgery has an adverse impact on surgical outcomes, yet the mechanisms through which this occurs are poorly defined. In this review, the evidence for bowel preparation strategies is critically appraised in the context of the gut microbiome. The impact of antibiotic therapy on the surgical gut microbiome and the importance of the intestinal "resistome" to surgical recovery is described. Data to support the augmentation of the microbiome through diet, probiotic and symbiotic approaches, as well as fecal transplantation are also appraised. Finally, we propose a novel strategy of bowel preparation defined as " surgical bioresilience " and define areas or prioritization in this emerging field. This describes the optimization of surgical intestinal homeostasis and core surgical exposome-microbiome interactions that regulate the wound immune microenvironment, the systemic inflammatory response to surgical injury, and gut function across the perioperative time course.}, }
@article {pmid36844708, year = {2023}, author = {Cheng, YW and Fischer, M}, title = {Fecal Microbiota Transplantation.}, journal = {Clinics in colon and rectal surgery}, volume = {36}, number = {2}, pages = {151-156}, pmid = {36844708}, issn = {1531-0043}, abstract = {Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a patient for therapeutic purposes. Current guidelines recommend FMT for the prevention of multiply recurrent Clostridioides difficile infection (CDI) after two recurrences, with cure rates approaching 90%. Emerging evidence also supports the use of FMT in the management of severe and fulminant CDI, resulting in decreased mortality and colectomy rates compared with standard of care approach. FMT shows promise as salvage therapy for critically-ill, refractory CDI patients who are poor surgical candidates. FMT should be considered early in the clinical course of severe CDI, preferably within 48 hours of failing to respond to antibiotic therapy and volume resuscitation. Besides CDI, ulcerative colitis was more recently identified as a potential treatment target for FMT. Several live biotherapeutics for microbiome restoration are on the horizon.}, }
@article {pmid36839510, year = {2023}, author = {Brumfield, KD and Cox, P and Geyer, J and Goepp, J}, title = {A Taxonomy-Agnostic Approach to Targeted Microbiome Therapeutics-Leveraging Principles of Systems Biology.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {36839510}, issn = {2076-0817}, abstract = {The study of human microbiomes has yielded insights into basic science, and applied therapeutics are emerging. However, conflicting definitions of what microbiomes are and how they affect the health of the "host" are less understood. A major impediment towards systematic design, discovery, and implementation of targeted microbiome therapeutics is the continued reliance on taxonomic indicators to define microbiomes in health and disease. Such reliance often confounds analyses, potentially suggesting associations where there are none, and conversely failing to identify significant, causal relationships. This review article discusses recent discoveries pointing towards a molecular understanding of microbiome "dysbiosis" and away from a purely taxonomic approach. We highlight the growing role of systems biological principles in the complex interrelationships between the gut microbiome and host cells, and review current approaches commonly used in targeted microbiome therapeutics, including fecal microbial transplant, bacteriophage therapies, and the use of metabolic toxins to selectively eliminate specific taxa from dysbiotic microbiomes. These approaches, however, remain wholly or partially dependent on the bacterial taxa involved in dysbiosis, and therefore may not capitalize fully on many therapeutic opportunities presented at the bioactive molecular level. New technologies capable of addressing microbiome-associated diseases as molecular problems, if solved, will open possibilities of new classes and categories of targeted microbiome therapeutics aimed, in principle, at all dysbiosis-driven disorders.}, }
@article {pmid36838416, year = {2023}, author = {Eribo, OA and Naidoo, CC and Theron, G and Walzl, G and du Plessis, N and Chegou, NN}, title = {An Archetypical Model for Engrafting Bacteroides fragilis into Conventional Mice Following Reproducible Antibiotic Conditioning of the Gut Microbiota.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, pmid = {36838416}, issn = {2076-2607}, support = {K43 TW012302/TW/FIC NIH HHS/United States ; R01 AI136894/AI/NIAID NIH HHS/United States ; }, abstract = {Bacteroides fragilis is a commonly investigated commensal bacterium for its protective role in host diseases. Here, we aimed to develop a reproducible antibiotic-based model for conditioning the gut microbiota and engrafting B. fragilis into a conventional murine host. Initially, we selected different combinations of antibiotics, including metronidazole, imipenem, and clindamycin, and investigated their efficacy in depleting the mouse Bacteroides population. We performed 16S rRNA sequencing of DNA isolated from fecal samples at different time points. The α-diversity was similar in mice treated with metronidazole (MET) and differed only at weeks 1 (p = 0.001) and 3 (p = 0.009) during metronidazole/imipenem (MI) treatment. Bacteroides compositions, during the MET and MI exposures, were similar to the pre-antibiotic exposure states. Clindamycin supplementation added to MET or MI regimens eliminated the Bacteroides population. We next repeated metronidazole/clindamycin (MC) treatment in two additional independent experiments, followed by a B. fragilis transplant. MC consistently and reproducibly eliminated the Bacteroides population. The depleted Bacteroides did not recover in a convalescence period of six weeks post-MC treatment. Finally, B. fragilis was enriched for ten days following engraftment into Bacteroides-depleted mice. Our model has potential use in gut microbiota studies that selectively investigate Bacteroides' role in diseases of interest.}, }
@article {pmid36838352, year = {2023}, author = {Bainum, TB and Reveles, KR and Hall, RG and Cornell, K and Alvarez, CA}, title = {Controversies in the Prevention and Treatment of Clostridioides difficile Infection in Adults: A Narrative Review.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, pmid = {36838352}, issn = {2076-2607}, support = {UL1 TR003163/TR/NCATS NIH HHS/United States ; }, abstract = {Clostridioides difficile remains a problematic pathogen resulting in significant morbidity and mortality, especially for high-risk groups that include immunocompromised patients. Both the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA), as well as the American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recently provided guideline updates for C. difficile infection (CDI). In this narrative review, the authors reviewed available literature regarding the prevention or treatment of CDI in adults and focused on disagreements between the IDSA/SHEA and ACG guidelines, as well as articles that have been published since the updates. Several options for primary prophylaxis are available, including probiotics and antibiotics (vancomycin, fidaxomicin). The literature supporting fidaxomicin is currently quite limited. While there are more studies evaluating probiotics and vancomycin, the optimal patient populations and regimens for their use have yet to be defined. While the IDSA/SHEA guidelines discourage metronidazole use for mild CDI episodes, evidence exists that it may remain a reasonable option for these patients. Fidaxomicin has an advantage over vancomycin in reducing recurrences, but its use is limited by cost. Despite this, recent studies suggest fidaxomicin's cost-effectiveness as a first-line therapy, though this is highly dependent on institutional contracts and payment structures. Secondary prophylaxis should focus on non-antimicrobial options to lessen the impact on the microbiome. The oral option of fecal microbiota transplantation (FMT), SER109, and the now FDA-approved RBX2660 represent exciting new options to correct dysbiosis. Bezlotoxumab is another attractive option to prevent recurrences. Further head-to-head studies of newer agents will be needed to guide selection of the optimal therapies for CDI primary and secondary prophylaxis.}, }
@article {pmid36838196, year = {2023}, author = {Loublier, C and Taminiau, B and Heinen, J and Lecoq, L and Amory, H and Daube, G and Cesarini, C}, title = {Evaluation of Bacterial Composition and Viability of Equine Feces after Processing for Transplantation.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, pmid = {36838196}, issn = {2076-2607}, support = {R.CFRA.35 90//University of Li&#xe8;ge/ ; }, abstract = {Fecal microbiota transplantation (FMT) has been used empirically for decades in equine medicine to treat intestinal dysbiosis but evidence-based information is scarce. This in vitro study aimed at assessing the effect of a commonly used pre-FMT processing method on the bacterial composition and viability of the fecal filtrate. Three samples of fresh equine manure (T0) were processed identically: the initial manure was mixed with 1 L of lukewarm water and chopped using an immersion blender to obtain a mixture (T1), which was left uncovered during 30 min (T2) and percolated through a sieve to obtain a fecal filtrate (T3). Samples were taken throughout the procedure (Tn) and immediately stored at 4 °C until processing. The 16S rDNA amplicon profiling associated with propidium monoazide treatment was performed on each sample to select live bacteria. Analyses of α and β diversity and main bacterial populations and quantitative (qPCR) analysis were performed and statistically compared (significance p < 0.05) between time points (T0-T3). No significant differences in ecological indices or mean estimated total living bacteria were found in the final fecal filtrate (T3) in regard to the original manure (T0); however, relative abundances of some minor genera (Fibrobacter, WCHB1-41_ge and Akkermansia) were significantly different in the final filtrate. In conclusion, the results support the viability of the major bacterial populations in equine feces when using the described pre-FMT protocol.}, }
@article {pmid36837875, year = {2023}, author = {Katsimichas, T and Theofilis, P and Tsioufis, K and Tousoulis, D}, title = {Gut Microbiota and Coronary Artery Disease: Current Therapeutic Perspectives.}, journal = {Metabolites}, volume = {13}, number = {2}, pages = {}, pmid = {36837875}, issn = {2218-1989}, abstract = {The human gut microbiota is the community of microorganisms living in the human gut. This microbial ecosystem contains bacteria beneficial to their host and plays important roles in human physiology, participating in energy harvest from indigestible fiber, vitamin synthesis, and regulation of the immune system, among others. Accumulating evidence suggests a possible link between compositional and metabolic aberrations of the gut microbiota and coronary artery disease in humans. Manipulating the gut microbiota through targeted interventions is an emerging field of science, aiming at reducing the risk of disease. Among the interventions with the most promising results are probiotics, prebiotics, synbiotics, and trimethylamine N-oxide (TMAO) inhibitors. Contemporary studies of probiotics have shown an improvement of inflammation and endothelial cell function, paired with attenuated extracellular matrix remodeling and TMAO production. Lactobacilli, Bifidobacteria, and Bacteroides are some of the most well studied probiotics in experimental and clinical settings. Prebiotics may also decrease inflammation and lead to reductions in blood pressure, body weight, and hyperlipidemia. Synbiotics have been associated with an improvement in glucose homeostasis and lipid abnormalities. On the contrary, no evidence yet exists on the possible benefits of postbiotic use, while the use of antibiotics is not warranted, due to potentially deleterious effects. TMAO inhibitors such as 3,3-dimethyl-1-butanol, iodomethylcholine, and fluoromethylcholine, despite still being investigated experimentally, appear to possess anti-inflammatory, antioxidant, and anti-fibrotic properties. Finally, fecal transplantation carries conflicting evidence, mandating the need for further research. In the present review we summarize the links between the gut microbiota and coronary artery disease and elaborate on the varied therapeutic measures that are being explored in this context.}, }
@article {pmid36836454, year = {2023}, author = {Stadlbauer, V}, title = {Liver-Gut-Interaction: Role of Microbiome Transplantation in the Future Treatment of Metabolic Disease.}, journal = {Journal of personalized medicine}, volume = {13}, number = {2}, pages = {}, pmid = {36836454}, issn = {2075-4426}, abstract = {The association between shifts in gut microbiome composition and metabolic disorders is a well-recognized phenomenon. Clinical studies and experimental data suggest a causal relationship, making the gut microbiome an attractive therapeutic goal. Fecal microbiome transplantation (FMT) is a method to alter a person's microbiome composition. Although this method allowed for the establishment of proof of concept for using microbiome modulation to treat metabolic disorders, the method is not yet ready for broad application. It is a resource-intensive method that also carries some procedural risks and whose effects are not always reproducible. This review summarizes the current knowledge on FMT to treat metabolic diseases and gives an outlook on open research questions. Further research is undoubtedly required to find applications that are less resource-intensive, such as oral encapsulated formulations, and have strong and predictable results. Furthermore, a clear commitment from all stakeholders is necessary to move forward in the direction of developing live microbial agents, next-generation probiotics, and targeted dietary interventions.}, }
@article {pmid36836218, year = {2023}, author = {Zhao, Y and Gong, C and Xu, J and Chen, D and Yang, B and Chen, Z and Wei, L}, title = {Research Progress of Fecal Microbiota Transplantation in Liver Diseases.}, journal = {Journal of clinical medicine}, volume = {12}, number = {4}, pages = {}, pmid = {36836218}, issn = {2077-0383}, abstract = {A growing body of evidence suggested that gut microbiota is associated with liver diseases through the gut-liver axis. The imbalance of gut microbiota could be correlated with the occurrence, development, and prognosis of a series of liver diseases, including alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, primary sclerosing cholangitis (PSC), and hepatocellular carcinoma (HCC). Fecal microbiota transplantation (FMT) seems to be a method to normalize the patient's gut microbiota. This method has been traced back to the 4th century. In recent decade, FMT has been highly regarded in several clinical trials. As a novel approach to reconstruct the intestinal microecological balance, FMT has been used to treat the chronic liver diseases. Therefore, in this review, the role of FMT in the treatment of liver diseases was summarized. In addition, the relationship between gut and liver was explored through the gut-liver axis, and the definition, objectives, advantages, and procedures of FMT were described. Finally, the clinical value of FMT therapy in liver transplant (LT) recipients was briefly discussed.}, }
@article {pmid36836185, year = {2023}, author = {Tiwari, P and Dwivedi, R and Bansal, M and Tripathi, M and Dada, R}, title = {Role of Gut Microbiota in Neurological Disorders and Its Therapeutic Significance.}, journal = {Journal of clinical medicine}, volume = {12}, number = {4}, pages = {}, pmid = {36836185}, issn = {2077-0383}, abstract = {In humans, the gut microbiota (GM) are known to play a significant role in the metabolism of nutrients and drugs, immunomodulation, and pathogen defense by inhabiting the gastrointestinal tract (GIT). The role of the GM in the gut-brain axis (GBA) has been documented for different regulatory mechanisms and associated pathways and it shows different behaviors with individualized bacteria. In addition, the GM are known as susceptibility factor for neurological disorders in the central nervous system (CNS), regulating disease progression and being amenable to intervention. Bidirectional transmission between the brain and the GM occurs in the GBA, implying that it performs a significant role in neurocrine, endocrine, and immune-mediated signaling pathways. The GM regulates multiple neurological disorders by supplementing them with prebiotics, probiotics, postbiotics, synbiotics, fecal transplantations, and/or antibiotics. A well-balanced diet is critically important for establishing healthy GM, which can alter the enteric nervous system (ENS) and regulate multiple neurological disorders. Here, we have discussed the function of the GM in the GBA from the gut to the brain and the brain to the gut, the pathways associated with neurology that interacts with the GM, and the various neurological disorders associated with the GM. Furthermore, we have highlighted the recent advances and future prospects of the GBA, which may require addressing research concerns about GM and associated neurological disorders.}, }
@article {pmid36835989, year = {2023}, author = {Singh, S and Pal, N and Shubham, S and Sarma, DK and Verma, V and Marotta, F and Kumar, M}, title = {Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics.}, journal = {Journal of clinical medicine}, volume = {12}, number = {4}, pages = {}, pmid = {36835989}, issn = {2077-0383}, abstract = {Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, typically characterized by anovulation, infertility, obesity, insulin resistance, and polycystic ovaries. Lifestyle or diet, environmental pollutants, genetics, gut dysbiosis, neuroendocrine alterations, and obesity are among the risk factors that predispose females to PCOS. These factors might contribute to upsurging metabolic syndrome by causing hyperinsulinemia, oxidative stress, hyperandrogenism, impaired folliculogenesis, and irregular menstrual cycles. Dysbiosis of gut microbiota may play a pathogenic role in the development of PCOS. The restoration of gut microbiota by probiotics, prebiotics, or a fecal microbiota transplant (FMT) might serve as an innovative, efficient, and noninvasive way to prevent and mitigate PCOS. This review deliberates on the variety of risk factors potentially involved in the etiology, prevalence, and modulation of PCOS, in addition to plausible therapeutic interventions, including miRNA therapy and the eubiosis of gut microbiota, that may help treat and manage PCOS.}, }
@article {pmid36835245, year = {2023}, author = {Haneishi, Y and Furuya, Y and Hasegawa, M and Picarelli, A and Rossi, M and Miyamoto, J}, title = {Inflammatory Bowel Diseases and Gut Microbiota.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835245}, issn = {1422-0067}, support = {JP22K17771//Japan Society for the Promotion of Science/ ; None//the Uehara Memorial Foundation/ ; None//the Lotte Foundation/ ; None//the Astellas Foundation for Research on Metabolic Disorders/ ; None//the Asahi Glass Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases ; *Microbiota ; *Probiotics ; Bacteria ; Fecal Microbiota Transplantation ; Dysbiosis/microbiology ; }, abstract = {Inflammatory bowel disease (IBD) is an inflammatory disease of the gastrointestinal tract, the incidence of which has rapidly increased worldwide, especially in developing and Western countries. Recent research has suggested that genetic factors, the environment, microbiota, and immune responses are involved in the pathogenesis; however, the underlying causes of IBD are unclear. Recently, gut microbiota dysbiosis, especially a decrease in the abundance and diversity of specific genera, has been suggested as a trigger for IBD-initiating events. Improving the gut microbiota and identifying the specific bacterial species in IBD are essential for understanding the pathogenesis and treatment of IBD and autoimmune diseases. Here, we review the different aspects of the role played by gut microbiota in the pathogenesis of IBD and provide a theoretical basis for modulating gut microbiota through probiotics, fecal microbiota transplantation, and microbial metabolites.}, }
@article {pmid36834904, year = {2023}, author = {Stec, A and Sikora, M and Maciejewska, M and Paralusz-Stec, K and Michalska, M and Sikorska, E and Rudnicka, L}, title = {Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36834904}, issn = {1422-0067}, support = {POWR.03.05.00-00-Z040/18-00//Medical University of Warsaw/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dermatitis, Atopic ; *Microbiota ; Bacteria/metabolism ; Fatty Acids, Volatile/metabolism ; Dysbiosis/microbiology ; }, abstract = {Dysbiosis has been identified in many dermatological conditions (e.g., psoriasis, atopic dermatitis, systemic lupus erythematosus). One of the ways by which the microbiota affect homeostasis is through microbiota-derived molecules (metabolites). There are three main groups of metabolites: short-chain fatty acids (SCFAs), tryptophan metabolites, and amine derivatives including trimethylamine N-oxide (TMAO). Each group has its own uptake and specific receptors through which these metabolites can exert their systemic function. This review provides up-to-date knowledge about the impact that these groups of gut microbiota metabolites may have in dermatological conditions. Special attention is paid to the effect of microbial metabolites on the immune system, including changes in the profile of the immune cells and cytokine disbalance, which are characteristic of several dermatological diseases, especially psoriasis and atopic dermatitis. Targeting the production of microbiota metabolites may serve as a novel therapeutic approach in several immune-mediated dermatological diseases.}, }
@article {pmid36832398, year = {2023}, author = {Tain, YL and Hsu, CN}, title = {Role of the Gut Microbiota in Children with Kidney Disease.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {36832398}, issn = {2227-9067}, support = {CMRPG8M0721 and CMRPG8M0751//Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan/ ; }, abstract = {Disruption of the composition and structure of the gut microbiota, namely dysbiosis, dictates the pathophysiology of kidney diseases. The bidirectional kidney-gut axis is of interest in chronic kidney disease (CKD); the uremic milieu leads to intestinal dysbiosis and gut microbial metabolites and toxins implicated in the loss of kidney function and increased comorbidity burden. Considering that kidney diseases can originate in childhood or even earlier in fetal life, identification of the pathogenetic connection between gut microbiota dysbiosis and the development of pediatric renal diseases deserves more attention. This review concentrates on the pathogenic link between dysbiotic gut microbiota and pediatric renal diseases, covering CKD, kidney transplantation, hemodialysis and peritoneal dialysis, and idiopathic nephrotic syndrome. Gut microbiota-targeted therapies including dietary intervention, probiotics, prebiotics, postbiotics and fecal microbial transplantation are discussed for their potential for the treatment of pediatric renal diseases. A deeper understanding of gut microbiota in pediatric renal diseases will aid in developing innovative gut microbiota-targeted interventions for preventing or attenuating the global burden of kidney diseases.}, }
@article {pmid36831641, year = {2023}, author = {Gholami, H and Chmiel, JA and Burton, JP and Maleki Vareki, S}, title = {The Role of Microbiota-Derived Vitamins in Immune Homeostasis and Enhancing Cancer Immunotherapy.}, journal = {Cancers}, volume = {15}, number = {4}, pages = {}, pmid = {36831641}, issn = {2072-6694}, support = {389137/CAPMC/CIHR/Canada ; IDI program//Western University/ ; }, abstract = {Not all cancer patients who receive immunotherapy respond positively and emerging evidence suggests that the gut microbiota may be linked to treatment efficacy. Though mechanisms of microbial contributions to the immune response have been postulated, one likely function is the supply of basic co-factors to the host including selected vitamins. Bacteria, fungi, and plants can produce their own vitamins, whereas humans primarily obtain vitamins from exogenous sources, yet despite the significance of microbial-derived vitamins as crucial immune system modulators, the microbiota is an overlooked source of these nutrients in humans. Microbial-derived vitamins are often shared by gut bacteria, stabilizing bioenergetic pathways amongst microbial communities. Compositional changes in gut microbiota can affect metabolic pathways that alter immune function. Similarly, the immune system plays a pivotal role in maintaining the gut microbiota, which parenthetically affects vitamin biosynthesis. Here we elucidate the immune-interactive mechanisms underlying the effects of these microbially derived vitamins and how they can potentially enhance the activity of immunotherapies in cancer.}, }
@article {pmid36831449, year = {2023}, author = {Knight, A and Karapetyan, L and Kirkwood, JM}, title = {Immunotherapy in Melanoma: Recent Advances and Future Directions.}, journal = {Cancers}, volume = {15}, number = {4}, pages = {}, pmid = {36831449}, issn = {2072-6694}, abstract = {The use of immunotherapy in the treatment of advanced and high-risk melanoma has led to a striking improvement in outcomes. Although the incidence of melanoma has continued to rise, median survival has improved from approximately 6 months to nearly 6 years for patients with advanced inoperable stage IV disease. Recent understanding of the tumor microenvironment and its interplay with the immune system has led to the explosive development of novel immunotherapy treatments. Since the approval of the therapeutic cytokines interleukin-2 and interferon alfa-2 in the 1990s, the development of novel immune checkpoint inhibitors (ICIs), oncolytic virus therapy, and modulators of the tumor microenvironment have given way to a new era in melanoma treatment. Monoclonal antibodies directed at programmed cell death protein 1 receptor (PD-1) and its ligand (PDL-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) have provided robust activation of the adaptive immune system, restoring immune surveillance leading to host tumor recognition and destruction. Multiple other immunomodulatory therapeutics are under investigation to overcome resistance to ICI therapy, including the toll-like receptor-9 (TLR-9) and 7/8 (TLR-7/8) agonists, stimulator of interferon genes (STING) agonists, and fecal microbiota transplantation. In this review, we focus on the recent advances in immunotherapy for the treatment of melanoma and provide an update on novel therapies currently under investigation.}, }
@article {pmid36830830, year = {2023}, author = {Campbell, C and Kandalgaonkar, MR and Golonka, RM and Yeoh, BS and Vijay-Kumar, M and Saha, P}, title = {Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy.}, journal = {Biomedicines}, volume = {11}, number = {2}, pages = {}, pmid = {36830830}, issn = {2227-9059}, support = {854385//Crohn's and Colitis Foundation/ ; 855256//American Heart Association (AHA)/ ; }, abstract = {Gut microbes and their metabolites are actively involved in the development and regulation of host immunity, which can influence disease susceptibility. Herein, we review the most recent research advancements in the gut microbiota-immune axis. We discuss in detail how the gut microbiota is a tipping point for neonatal immune development as indicated by newly uncovered phenomenon, such as maternal imprinting, in utero intestinal metabolome, and weaning reaction. We describe how the gut microbiota shapes both innate and adaptive immunity with emphasis on the metabolites short-chain fatty acids and secondary bile acids. We also comprehensively delineate how disruption in the microbiota-immune axis results in immune-mediated diseases, such as gastrointestinal infections, inflammatory bowel diseases, cardiometabolic disorders (e.g., cardiovascular diseases, diabetes, and hypertension), autoimmunity (e.g., rheumatoid arthritis), hypersensitivity (e.g., asthma and allergies), psychological disorders (e.g., anxiety), and cancer (e.g., colorectal and hepatic). We further encompass the role of fecal microbiota transplantation, probiotics, prebiotics, and dietary polyphenols in reshaping the gut microbiota and their therapeutic potential. Continuing, we examine how the gut microbiota modulates immune therapies, including immune checkpoint inhibitors, JAK inhibitors, and anti-TNF therapies. We lastly mention the current challenges in metagenomics, germ-free models, and microbiota recapitulation to a achieve fundamental understanding for how gut microbiota regulates immunity. Altogether, this review proposes improving immunotherapy efficacy from the perspective of microbiome-targeted interventions.}, }
@article {pmid36830185, year = {2023}, author = {Helmy, YA and Taha-Abdelaziz, K and Hawwas, HAE and Ghosh, S and AlKafaas, SS and Moawad, MMM and Saied, EM and Kassem, II and Mawad, AMM}, title = {Antimicrobial Resistance and Recent Alternatives to Antibiotics for the Control of Bacterial Pathogens with an Emphasis on Foodborne Pathogens.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {36830185}, issn = {2079-6382}, abstract = {Antimicrobial resistance (AMR) is one of the most important global public health problems. The imprudent use of antibiotics in humans and animals has resulted in the emergence of antibiotic-resistant bacteria. The dissemination of these strains and their resistant determinants could endanger antibiotic efficacy. Therefore, there is an urgent need to identify and develop novel strategies to combat antibiotic resistance. This review provides insights into the evolution and the mechanisms of AMR. Additionally, it discusses alternative approaches that might be used to control AMR, including probiotics, prebiotics, antimicrobial peptides, small molecules, organic acids, essential oils, bacteriophage, fecal transplants, and nanoparticles.}, }
@article {pmid36830173, year = {2023}, author = {Maeda, Y and Murakami, T}, title = {Diagnosis by Microbial Culture, Breath Tests and Urinary Excretion Tests, and Treatments of Small Intestinal Bacterial Overgrowth.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {36830173}, issn = {2079-6382}, abstract = {Small intestinal bacterial overgrowth (SIBO) is characterized as the increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract and accompanies various bowel symptoms such as abdominal pain, bloating, gases, diarrhea, and so on. Clinically, SIBO is diagnosed by microbial culture in duodenum/jejunum fluid aspirates and/or the breath tests (BT) of hydrogen/methane gases after ingestion of carbohydrates such as glucose. The cultural analysis of aspirates is regarded as the golden standard for the diagnosis of SIBO; however, this is invasive and is not without risk to the patients. BT is an inexpensive and safe diagnostic test but lacks diagnostic sensitivity and specificity depending on the disease states of patients. Additionally, the urinary excretion tests are used for the SIBO diagnosis using chemically synthesized bile acid conjugates such as cholic acid (CA) conjugated with para-aminobenzoic acid (PABA-CA), ursodeoxycholic acid (UDCA) conjugated with PABA (PABA-UDCA) or conjugated with 5-aminosalicylic acid (5-ASA-UDCA). These conjugates are split by bacterial bile acid (cholylglycine) hydrolase. In the tests, the time courses of the urinary excretion rates of PABA or 5-ASA, including their metabolites, are determined as the measure of hydrolytic activity of intestinal bacteria. Although the number of clinical trials with this urinary excretion tests is small, results demonstrated the usefulness of bile acid conjugates as SIBO diagnostic substrates. PABA-UDCA disulfate, a single-pass type unabsorbable compound without the hydrolysis of conjugates, was likely to offer a simple and rapid method for the evaluation of SIBO without the use of radioisotopes or expensive special apparatus. Treatments of SIBO with antibiotics, probiotics, therapeutic diets, herbal medicines, and/or fecal microbiota transplantation are also reviewed.}, }
@article {pmid36829082, year = {2023}, author = {Janczy, A and Szymanski, M and Stankiewicz, M and Kaska, L and Waleron, K and Stelmanska, E and Sledzinski, T and Mika, A}, title = {Increased Amount of Polyunsaturated Fatty Acids in the Intestinal Contents of Patients with Morbid Obesity.}, journal = {Obesity surgery}, volume = {33}, number = {4}, pages = {1228-1236}, pmid = {36829082}, issn = {1708-0428}, mesh = {Humans ; Gastrointestinal Contents ; *Obesity, Morbid/surgery ; Fatty Acids, Unsaturated ; Fatty Acids/metabolism ; *Fatty Acids, Omega-3 ; }, abstract = {INTRODUCTION: Obesity is associated with disturbed gut microbiota homeostasis that translates into altered intestinal and blood metabolite profiles. The long-chain fatty acid (LCFA) may be absorbed in the intestine, but until now, their composition in intestinal contents of patients with obesity has not been studied. The aim of the present study was to verify whether obesity is related to any changes in fecal LCFA content and whether intestinal LCFA content may be associated with the health status of patients with obesity.<br><br>METHODS: The fatty acid composition has been studied in stool samples obtained from 26 patients with morbid obesity and 25 lean subjects by gas chromatography-mass spectrometry. The dietary habits were assessed using the Food Frequency Questionnaire (FFQ-6).<br><br>RESULTS: Our results show for the first time that lean subjects and patients with obesity differ in their stool LCFA profiles. The levels of most n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs were significantly higher in fecal samples from people with obesity than in those from lean controls.<br><br>CONCLUSIONS: Based on the current knowledge, we have defined three hypotheses that may explain proving the cause-and-effect relationships observed differences in fecal LCFA profiles between patients with obesity and lean subjects. They may be related to alterations in fat digestion and/or LCFA absorption and diet. However, proving the cause-and-effect relationships requires further research.}, }
@article {pmid36828429, year = {2023}, author = {Caggiano, G and Stasi, A and Franzin, R and Fiorentino, M and Cimmarusti, MT and Deleonardis, A and Palieri, R and Pontrelli, P and Gesualdo, L}, title = {Fecal Microbiota Transplantation in Reducing Uremic Toxins Accumulation in Kidney Disease: Current Understanding and Future Perspectives.}, journal = {Toxins}, volume = {15}, number = {2}, pages = {}, pmid = {36828429}, issn = {2072-6651}, mesh = {Humans ; Uremic Toxins ; Fecal Microbiota Transplantation ; *Renal Insufficiency, Chronic/metabolism ; Dysbiosis ; *Gastrointestinal Microbiome ; }, abstract = {During the past decades, the gut microbiome emerged as a key player in kidney disease. Dysbiosis-related uremic toxins together with pro-inflammatory mediators are the main factors in a deteriorating kidney function. The toxicity of uremic compounds has been well-documented in a plethora of pathophysiological mechanisms in kidney disease, such as cardiovascular injury (CVI), metabolic dysfunction, and inflammation. Accumulating data on the detrimental effect of uremic solutes in kidney disease supported the development of many strategies to restore eubiosis. Fecal microbiota transplantation (FMT) spread as an encouraging treatment for different dysbiosis-associated disorders. In this scenario, flourishing studies indicate that fecal transplantation could represent a novel treatment to reduce the uremic toxins accumulation. Here, we present the state-of-the-art concerning the application of FMT on kidney disease to restore eubiosis and reverse the retention of uremic toxins.}, }
@article {pmid36828341, year = {2023}, author = {Liu, L and Zhang, T and Sui, Y and Li, G and Liu, L and Lu, T and Tan, H and Sun, B and Li, X and Li, L}, title = {Gut microbiota affects pancreatic fibrotic progression through immune modulation in chronic pancreatitis.}, journal = {Microbial pathogenesis}, volume = {177}, number = {}, pages = {106035}, doi = {10.1016/j.micpath.2023.106035}, pmid = {36828341}, issn = {1096-1208}, mesh = {Humans ; Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; *Pancreatitis, Chronic/microbiology ; Feces/microbiology ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Fibrosis ; }, abstract = {Chronic pancreatitis (CP) is characterized by chronic progressive pancreatic inflammation, which leads to the permanent damage of exocrine and endocrine cells. CP causes irreversible morphological and functional changes, and the clinical manifestations includes abdomen pain, steatorrhea and diabetes. CP induces changes in the composition of gut microbiota that could be used as potential biomarkers for pancreatic fibrosis evaluation. Gut microbiota has emerged as key regulator of immunomodulation and gut microbiota-induced immune activation has not been explored in CP. In current study, we profiled gut microbial signatures in mouse CP model, and found that higher proportion of Streptomyces, Turicibacter, Methylobacterium, Enterococcus and Candidatus_Paenicardiniummore were positively associated with the occurrence of pancreatic fibrosis. We then identified increased CD3[+]T cells and macrophage infiltration in mouse and human CP tissues by transcriptome sequencing data from GEO database. Subsequently, we demonstrated that fecal microbiota transplantation (FMT) from CP mouse (FMT-CP) exacerbated pancreatic fibrosis by increasing CD4[+]T cells and macrophage infiltration compared to fecal samples obtained from healthy mouse donor (FMT-HC). Our study describes the link between gut microbiota dysbiosis and immune activation in pancreatic fibrotic progression, and highlights the potential therapeutic roles of FMT and CP treatment.}, }
@article {pmid36825261, year = {2022}, author = {Ohkusa, T and Nishikawa, Y and Sato, N}, title = {Gastrointestinal disorders and intestinal bacteria: Advances in research and applications in therapy.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {935676}, pmid = {36825261}, issn = {2296-858X}, abstract = {Intestinal bacteria coexist with humans and play a role in suppressing the invasion of pathogens, producing short-chain fatty acids, producing vitamins, and controlling the immune system. Studies have been carried out on culturable bacterial species using bacterial culture methods for many years. However, as metagenomic analysis of bacterial genes has been developed since the 1990s, it has recently revealed that many bacteria in the intestine cannot be cultured and that approximately 1,000 species and 40 trillion bacteria are present in the gut microbiota. Furthermore, the composition of the microbiota is different in each disease state compared with the healthy state, and dysbiosis has received much attention as a cause of various diseases. Regarding gastrointestinal diseases, dysbiosis has been reported to be involved in inflammatory bowel disease, irritable bowel syndrome, and non-alcoholic steatohepatitis. Recent findings have also suggested that dysbiosis is involved in colon cancer, liver cancer, pancreatic cancer, esophageal cancer, and so on. This review focuses on the relationship between the gut microbiota and gastrointestinal/hepatobiliary diseases and also discusses new therapies targeting the gut microbiota.}, }
@article {pmid36825211, year = {2022}, author = {Hammond, TC and Messmer, S and Frank, JA and Lukins, D and Colwell, R and Lin, AL and Pennypacker, KR}, title = {Gut microbial dysbiosis correlates with stroke severity markers in aged rats.}, journal = {Frontiers in stroke}, volume = {1}, number = {}, pages = {}, pmid = {36825211}, issn = {2813-3056}, support = {RF1 AG062480/AG/NIA NIH HHS/United States ; S10 RR029541/RR/NCRR NIH HHS/United States ; T32 AG057461/AG/NIA NIH HHS/United States ; }, abstract = {BACKGROUND: An imbalanced gut microbial community, or dysbiosis, has been shown to occur following stroke. It is possible that this dysbiosis negatively impacts stroke recovery and rehabilitation. Species level resolution measurements of the gut microbiome following stroke are needed to develop and test precision interventions such as probiotic or fecal microbiota transplant therapies that target the gut microbiome. Previous studies have used 16S rRNA amplicon sequencing in young male mice to obtain broad profiling of the gut microbiome at the genus level following stroke, but further investigations will be needed with whole genome shotgun sequencing in aged rats of both sexes to obtain species level resolution in a model which will better translate to the demographics of human stroke patients.<br><br>METHODS: Thirty-nine aged male and female rats underwent middle cerebral artery occlusion. Fecal samples were collected before stroke and 3 days post stroke to measure gut microbiome. Machine learning was used to identify the top ranked bacteria which were changed following stroke. MRI imaging was used to obtain infarct and edema size and cerebral blood flow (CBF). ELISA was used to obtain inflammatory markers.<br><br>RESULTS: Dysbiosis was demonstrated by an increase in pathogenic bacteria such as Butyricimonas virosa (15.52 fold change, p < 0.0001), Bacteroides vulgatus (7.36 fold change, p < 0.0001), and Escherichia coli (47.67 fold change, p < 0.0001). These bacteria were positively associated with infarct and edema size and with the inflammatory markers Ccl19, Ccl24, IL17a, IL3, and complement C5; they were negatively correlated with CBF. Conversely, beneficial bacteria such as Ruminococcus flavefaciens (0.14 fold change, p < 0.0001), Akkermansia muciniphila (0.78 fold change, p < 0.0001), and Lactobacillus murinus (0.40 fold change, p < 0.0001) were decreased following stroke and associated with all the previous parameters in the opposite direction of the pathogenic species. There were not significant microbiome differences between the sexes.<br><br>CONCLUSION: The species level resolution measurements found here can be used as a foundation to develop and test precision interventions targeting the gut microbiome following stroke. Probiotics that include Ruminococcus flavefaciens, Akkermansia muciniphila, and Lactobacillus murinus should be developed to target the deficit following stroke to measure the impact on stroke severity.}, }
@article {pmid36821954, year = {2023}, author = {Ikeda, Y and Saigo, N and Nagasaki, Y}, title = {Direct evidence for the involvement of intestinal reactive oxygen species in the progress of depression via the gut-brain axis.}, journal = {Biomaterials}, volume = {295}, number = {}, pages = {122053}, doi = {10.1016/j.biomaterials.2023.122053}, pmid = {36821954}, issn = {1878-5905}, mesh = {Mice ; Animals ; *Depression/therapy/etiology ; Reactive Oxygen Species ; Brain-Gut Axis ; *Gastrointestinal Microbiome ; Brain/physiology ; }, abstract = {Depression is a serious global social problem. Various therapeutic drugs have been developed based on the monoamine hypothesis; however, treatment-resistant depression is a common clinical issue. Recently, the gut-brain axis, which is associated with the hypothesis that the intestinal environment affects the brain, has garnered significant interest, and several studies have attempted to treat brain disorders based on this axis. These attempts include fecal transplantation, probiotics and prebiotics. In this study, we focused on intestinal reactive oxygen species (ROS) because excessive ROS levels disturb the intestinal environment. To elucidate the impact of scavenging intestinal ROS on depression treatment via the gut-brain axis, a novel polymer-based antioxidant (siSMAPo[TN]), which was distributed only in the intestine and did not diffuse into the whole body after oral administration, was used. siSMAPo[TN] selectively scavenged intestinal ROS and protected the intestinal environment from damage caused by chronic restraint stress (CRS). In addition, siSMAPo[TN] suppressed physiological and behavioral depression-related symptoms in the CRS mouse model.}, }
@article {pmid36819586, year = {2023}, author = {Søfteland, JM}, title = {Modulation of the intestinal bacterial flora: a viable strategy to alleviate acute mesenteric ischemia?.}, journal = {Annals of translational medicine}, volume = {11}, number = {2}, pages = {30}, pmid = {36819586}, issn = {2305-5839}, }
@article {pmid36819429, year = {2023}, author = {Miró-González, &#xc1;A and Maldonado-Chaar, SM and Zambrana-Valenzuela, R and Iglesias-Escabi, IM and Arciniegas-Medina, NJ}, title = {Development of Very-Early-Onset Inflammatory Bowel Disease After Multiple Early-Life Antibiotic Exposures: A Case Report and Literature Review.}, journal = {Cureus}, volume = {15}, number = {1}, pages = {e33813}, pmid = {36819429}, issn = {2168-8184}, abstract = {The use of antibiotics has increased drastically over the last few decades. Many antibiotics can target the commensal microbiota and promote gut dysbiosis. These alterations contribute to disease onset and exacerbation. Although the etiology of inflammatory bowel disease (IBD) is mostly unknown, it involves a complex interaction among host genetics, microbiota, environmental factors, and aberrant immune responses. Studies have shown a relationship between very-early-onset inflammatory bowel disease (VEO-IBD) and microbiota alterations. The case discussed in this report endorses the current clinical evidence for this interaction. This is an anonymous record review with no identifiers involving a 23-month-old female patient who was brought to the emergency department by her parents due to persistent bloody diarrhea. Eight days before the presentation, she had experienced watery diarrhea that progressed to bloody stools. The patient had a history of acute otitis media, acute enteritis, and right-arm cutaneous abscess, for which she had received multiple antibiotic therapies. Strategies to manipulate the microbiome through diet, probiotics, antibiotics, or fecal microbiota transplantation (FMT) may be used therapeutically to modulate disease activity. A high index of clinical suspicion for VEO-IBD should be maintained for patients with a history of multiple, recurrent antibiotic use. We believe this case report will raise awareness about the issue of early anaerobic antibiotic exposure and help prevent its unnecessary use and, consequently, prevent gut microbiota dysbiosis that can lead to VEO-IBD. Also, our literature review will hopefully prompt clinicians to consider alternative therapeutic options for this patient population, such as rebuilding intestinal microbiota composition to improve VEO-IBD activity.}, }
@article {pmid36818228, year = {2023}, author = {Zhu, D and Jin, X and Guo, P and Sun, Y and Zhou, L and Qing, Y and Shen, W and Ji, G}, title = {Efficacy of Faecal Microbiota Transplantation for the Treatment of Autism in Children: Meta-Analysis of Randomised Controlled Trials.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2023}, number = {}, pages = {5993628}, pmid = {36818228}, issn = {1741-427X}, abstract = {OBJECTIVE: Evidence-based research methods were applied to assess the efficacy of faecal microbiota transplantation (FMT) for the treatment of autism in children.<br><br>METHODS: We searched the Chinese Biomedical Literature, CNKI, Wanfang, PubMed, Embase, Web of Science, and the Cochrane Library databases to collect randomised controlled trials on faecal microbiota transplantation for the treatment of autism in children. The search included studies published from the creation of the respective database to 5 April 2022. Literature screening, data extraction, and quality evaluation were implemented by three investigators according to the inclusion and exclusion criteria. The meta-analysis was performed using the RevMan 5.1 software.<br><br>RESULTS: Nine studies with population-based subjects and four studies with animal-based subjects were included. Five papers were screened for the meta-analysis. The results showed that FMT markedly reduced Autism Behaviour Checklist (ABC) scores in children with autism spectrum disorder (weighted mean difference (WMD)&#x2009;=&#x2009;-14.96; 95% confidence intervals (CI), -21.68 to -8.24; P < 0.001; I [2]&#x2009;=&#x2009;0%). FMT also reduced Childhood Autism Rating Scale (CARS) scores (WMD&#x2009;=&#x2009;-6.95; 95% CI, -8.76 to -5.14; P < 0.001; I [2]&#x2009;=&#x2009;28.1%).<br><br>CONCLUSION: Our results indicate that FMT can benefit children with autism by reducing ABC and CARS scores, but more high-quality studies are needed to verify these results.}, }
@article {pmid36816570, year = {2023}, author = {Wu, N and Li, X and Ma, H and Zhang, X and Liu, B and Wang, Y and Zheng, Q and Fan, X}, title = {The role of the gut microbiota and fecal microbiota transplantation in neuroimmune diseases.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1108738}, pmid = {36816570}, issn = {1664-2295}, abstract = {The gut microbiota plays a key role in the function of the host immune system and neuroimmune diseases. Alterations in the composition of the gut microbiota can lead to pathology and altered formation of microbiota-derived components and metabolites. A series of neuroimmune diseases, such as myasthenia gravis (MG), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), Guillain-Barré syndrome (GBS), and autoimmune encephalitis (AIE), are associated with changes in the gut microbiota. Microecological therapy by improving the gut microbiota is expected to be an effective measure for treating and preventing some neuroimmune diseases. This article reviews the research progress related to the roles of gut microbiota and fecal microbiota transplantation (FMT) in neuroimmune diseases.}, }
@article {pmid36816181, year = {2023}, author = {Jugan, MC and KuKanich, K and Freilich, L}, title = {Clinical response in dogs with acute hemorrhagic diarrhea syndrome following randomized probiotic treatment or fecal microbiota transplant.}, journal = {Frontiers in veterinary science}, volume = {10}, number = {}, pages = {1050538}, pmid = {36816181}, issn = {2297-1769}, abstract = {Probiotics and fecal microbiota transplants (FMTs) are two microbiome-targeted therapies that have been investigated for use in gastrointestinal diseases associated with dysbiosis. The aim of this study was to compare the effects of an oral multi-strain probiotic and enema-administered FMTs on clinical signs and serum lipopolysaccharide in dogs with acute hemorrhagic diarrhea syndrome (AHDS). A total of 18 client-owned dogs with a diagnosis of AHDS were enrolled in a randomized, blinded study at the time of hospital admission. The dogs were randomized into two groups: the probiotic group received a daily oral probiotic (200 × 10[9] CFU/10kg q 24 h) for 14 days and a single sham enema; the FMT group received a single FMT via retention enema (10 mL/kg) and placebo oral capsule for 14 days. All dogs received concurrent standard-of-care therapy, including intravenous fluids and anti-emetics; no dogs received antimicrobials. The fecal score, disease severity scores, and serum lipopolysaccharide were measured on days 0, 3, and 14. Fourteen of eighteen enrolled dogs completed the study (n = 9 probiotics; n = 5 FMT). Lipopolysaccharide decreased on days 3 and 14 from baseline and correlated with fecal and disease severity scores. There was no difference in the duration or severity of clinical signs in dogs with AHDS following an enema-administered FMT compared to probiotic treatment. Further evaluation of serum lipopolysaccharide as a marker of disease severity and recovery is warranted.}, }
@article {pmid36815880, year = {2023}, author = {Khan, RL and Khraibi, AA and Dumée, LF and Corridon, PR}, title = {From waste to wealth: Repurposing slaughterhouse waste for xenotransplantation.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {11}, number = {}, pages = {1091554}, pmid = {36815880}, issn = {2296-4185}, abstract = {Slaughterhouses produce large quantities of biological waste, and most of these materials are underutilized. In many published reports, the possibility of repurposing this form of waste to create biomaterials, fertilizers, biogas, and feeds has been discussed. However, the employment of particular offal wastes in xenotransplantation has yet to be extensively uncovered. Overall, viable transplantable tissues and organs are scarce, and developing bioartificial components using such discarded materials may help increase their supply. This perspective manuscript explores the viability and sustainability of readily available and easily sourced slaughterhouse waste, such as blood vessels, eyes, kidneys, and tracheas, as starting materials in xenotransplantation derived from decellularization technologies. The manuscript also examines the innovative use of animal stem cells derived from the excreta to create a bioartificial tissue/organ platform that can be translated to humans. Institutional and governmental regulatory approaches will also be outlined to support this endeavor.}, }
@article {pmid36814445, year = {2023}, author = {Liu, J and Lin, H and Cao, M and Lin, T and Lin, A and Xu, W and Wang, H and He, J and Li, Y and Tang, H and Zhang, B}, title = {Shifts and importance of viable bacteria in treatment of DSS-induced ulcerative colitis mice with FMT.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1124256}, pmid = {36814445}, issn = {2235-2988}, mesh = {Mice ; Humans ; Animals ; *Colitis, Ulcerative ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S ; Feces/microbiology ; Bacteria ; Dextran Sulfate ; *Colitis/therapy ; }, abstract = {BACKGROUND AND AIMS: Ulcerative colitis (UC) has become a global public health concern, and is in urgent need of novel therapies. Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of UC. Despite its recent successes, it is still largely unknown how FMT functionally modulates the gut microbiota and improves the disease.<br><br>METHODS: We prospectively collected fecal samples from the 40 mice (30 mice for dextran sulfate sodium (DSS)-induced, 10 for controls), followed by Propidium monoazide treatment for 16S rRNA gene sequencing. These 30 mice were divided equally into 3 groups, which were transplanted with original donor microbiota (DO), inactivated donor microbiota (DI) and saline, respectively. Subsequently, we used 16S rRNA gene sequencing to analyze the viable gut bacteria of ulcerative colitis (UC) mice and histological analysis to evaluate the effects of fecal microbiota transplantation (FMT) with viable microbiota.<br><br>RESULTS: We demonstrated that the community structure of viable bacteria was significantly different from fecal bacteria based on total DNA. Furthermore, the intestinal viable microbiota and colonic mucosal structure of mice were significantly changed by DSS induction. The histological analysis showed that only the mice treated with original donor microbiota group (HF) achieved a significant improvement. Compared with inactivated donor microbiota group (IF) and saline (NF), Lactobacillus and Halomonas were significantly enriched in the HF group.<br><br>CONCLUSION: We inferred that only live bacteria from human donor reversed the histopathology and symptoms of UC in mice and altered the gut microbiota. The activity of gut microbiota in donor samples should be considered in FMT and that detailed analysis of viable microbiota is essential to understand the mechanisms by which FMT produces therapeutic effects in the future.}, }
@article {pmid36814251, year = {2023}, author = {Rashidi, A and Koyama, M and Dey, N and McLean, JS and Hill, GR}, title = {Colonization resistance is dispensable for segregation of oral and gut microbiota.}, journal = {BMC medical genomics}, volume = {16}, number = {1}, pages = {31}, pmid = {36814251}, issn = {1755-8794}, mesh = {Humans ; *Gastrointestinal Microbiome ; Anti-Bacterial Agents/therapeutic use ; Feces/microbiology ; Bacteria ; *Inflammatory Bowel Diseases ; *Colonic Neoplasms ; }, abstract = {BACKGROUND: The oral and colonic microbiota are distinct in healthy individuals. However, this distinction is diminished in common diseases such as colon cancer and inflammatory bowel disease, suggesting a potential pathogenic role for oral bacteria when ectopically colonized in the gut. A key mechanism for the segregation of oral and colonic microbiota niches is thought to be microbiota-mediated colonization resistance whereby the commensal gut microbiota outcompete and eliminate the ingested oral bacteria.<br><br>METHODS: We tested this theory by analyzing exact amplicon sequence variants generated from concurrent fecal and oral samples from healthy volunteers exposed to a brief course of a single antibiotic (cohort 1), acute leukemia patients (cohort 2), and stem cell transplant recipients (cohort 3). Cohorts 2 and 3 represent extreme clinical scenarios with respect to antibiotic pressure and severity of gut microbiota injury.<br><br>RESULTS: While mild antibiotic exposure in cohort 1 was not sufficient for colonization of any oral bacteria in the gut, even with extreme antibiotic pressure and severe gut microbiota disruptions in cohorts 2 and 3, only one oral species in each cohort colonized the gut.<br><br>CONCLUSIONS: Colonization resistance is dispensable for segregation of oral and colonic microbiota in humans. This finding implies that the presence of oral bacteria in the distal gut in diseases such as colon cancer and inflammatory bowel disease is not driven by impaired colonization resistance.}, }
@article {pmid36813961, year = {2023}, author = {Tintelnot, J and Xu, Y and Lesker, TR and Schönlein, M and Konczalla, L and Giannou, AD and Pelczar, P and Kylies, D and Puelles, VG and Bielecka, AA and Peschka, M and Cortesi, F and Riecken, K and Jung, M and Amend, L and Bröring, TS and Trajkovic-Arsic, M and Siveke, JT and Renné, T and Zhang, D and Boeck, S and Strowig, T and Uzunoglu, FG and Güngör, C and Stein, A and Izbicki, JR and Bokemeyer, C and Sinn, M and Kimmelman, AC and Huber, S and Gagliani, N}, title = {Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer.}, journal = {Nature}, volume = {615}, number = {7950}, pages = {168-174}, pmid = {36813961}, issn = {1476-4687}, mesh = {Animals ; Humans ; Mice ; *Carcinoma, Pancreatic Ductal/diet therapy/drug therapy/metabolism/microbiology ; Glutathione Peroxidase/metabolism ; *Microbiota ; *Pancreatic Neoplasms/diet therapy/drug therapy/metabolism/microbiology ; Peroxidase/metabolism ; Reactive Oxygen Species/metabolism ; Tryptophan/metabolism/pharmacology/therapeutic use ; Neutrophils/enzymology ; Autophagy ; Metagenome ; Metabolomics ; Fecal Microbiota Transplantation ; Indoleacetic Acids/pharmacology/therapeutic use ; Disease Models, Animal ; Germ-Free Life ; }, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second most deadly cancer by 2040, owing to the high incidence of metastatic disease and limited responses to treatment[1,2]. Less than half of all patients respond to the primary treatment for PDAC, chemotherapy[3,4], and genetic alterations alone cannot explain this[5]. Diet is an environmental factor that can influence the response to therapies, but its role in PDAC is unclear. Here, using shotgun metagenomic sequencing and metabolomic screening, we show that the microbiota-derived tryptophan metabolite indole-3-acetic acid (3-IAA) is enriched in patients who respond to treatment. Faecal microbiota transplantation, short-term dietary manipulation of tryptophan and oral 3-IAA administration increase the efficacy of chemotherapy in humanized gnotobiotic mouse models of PDAC. Using a combination of loss- and gain-of-function experiments, we show that the efficacy of 3-IAA and chemotherapy is licensed by neutrophil-derived myeloperoxidase. Myeloperoxidase oxidizes 3-IAA, which in combination with chemotherapy induces a downregulation of the reactive oxygen species (ROS)-degrading enzymes glutathione peroxidase 3 and glutathione peroxidase 7. All of this results in the accumulation of ROS and the downregulation of autophagy in cancer cells, which compromises their metabolic fitness and, ultimately, their proliferation. In humans, we observed a significant correlation between the levels of 3-IAA and the efficacy of therapy in two independent PDAC cohorts. In summary, we identify a microbiota-derived metabolite that has clinical implications in the treatment of PDAC, and provide a motivation for considering nutritional interventions during the treatment of patients with cancer.}, }
@article {pmid36813004, year = {2023}, author = {Guo, L and Yin, X and Liu, Q}, title = {Fecal microbiota transplantation reduces mouse mortality from Listeria monocytogenes infection.}, journal = {Microbial pathogenesis}, volume = {178}, number = {}, pages = {106036}, doi = {10.1016/j.micpath.2023.106036}, pmid = {36813004}, issn = {1096-1208}, mesh = {Animals ; Mice ; Fecal Microbiota Transplantation ; *Listeria monocytogenes ; Feces/microbiology ; Gastrointestinal Tract ; *Gastrointestinal Microbiome ; *Listeriosis/therapy ; }, abstract = {Listeria monocytogenes (Lm) is a food bacterium with strong pathogenicity which causes infections via the gastrointestinal tract. Mechanisms by which gut microbiota (GM) resist microbial infections have received little attention. Eight-week-old mice were orally inoculated with wild-type Lm EGD-e and fecal microbiota transplantation (FMT) employed. GM richness and diversity of infected mice changed rapidly within 24h. Firmicutes class decreased and Bacteroidetes, Tenericutes and Ruminococcaceae increased significantly. Coprococcus, Blautia and Eubacterium also increased on the 3rd day post-infection. Moreover, GM transplanted from healthy mice reduced mortality of infected mice by approximately 32%. FMT treatment decreased production of TNFα, IFN-γ, IL-1β and IL-6 relative to PBS treatment. In summary, FMT has potential as a treatment against Lm infection and may be used for bacterial resistance management. Further work is required to elucidate the key GM effector molecules.}, }
@article {pmid36812497, year = {2023}, author = {Petrick, HL and Ogilvie, LM and Brunetta, HS and Robinson, A and Kirsh, AJ and Barbeau, PA and Handy, RM and Coyle-Asbil, B and Gianetto-Hill, C and Dennis, KMJH and van Loon, LJC and Chabowski, A and Schertzer, JD and Allen-Vercoe, E and Simpson, JA and Holloway, GP}, title = {Dietary Nitrate and Corresponding Gut Microbiota Prevent Cardiac Dysfunction in Obese Mice.}, journal = {Diabetes}, volume = {72}, number = {7}, pages = {844-856}, doi = {10.2337/db22-0575}, pmid = {36812497}, issn = {1939-327X}, mesh = {Male ; Mice ; Animals ; *Glucose Intolerance/prevention &amp; control ; *Gastrointestinal Microbiome/physiology ; Reactive Oxygen Species ; Mice, Obese ; Nitrates/pharmacology ; Dysbiosis/microbiology ; Obesity/metabolism ; Inflammation ; Diet, High-Fat/adverse effects ; Lipids ; *Heart Diseases ; Fibrosis ; *Hypertension ; Mice, Inbred C57BL ; }, abstract = {UNLABELLED: Impaired heart function can develop in individuals with diabetes in the absence of coronary artery disease or hypertension, suggesting mechanisms beyond hypertension/increased afterload contribute to diabetic cardiomyopathy. Identifying therapeutic approaches that improve glycemia and prevent cardiovascular disease are clearly required for clinical management of diabetes-related comorbidities. Since intestinal bacteria are important for metabolism of nitrate, we examined whether dietary nitrate and fecal microbial transplantation (FMT) from nitrate-fed mice could prevent high-fat diet (HFD)-induced cardiac abnormalities. Male C57Bl/6N mice were fed a low-fat diet (LFD), HFD, or HFD+Nitrate (4 mmol/L sodium nitrate) for 8 weeks. HFD-fed mice presented with pathological left ventricle (LV) hypertrophy, reduced stroke volume, and increased end-diastolic pressure, in association with increased myocardial fibrosis, glucose intolerance, adipose inflammation, serum lipids, LV mitochondrial reactive oxygen species (ROS), and gut dysbiosis. In contrast, dietary nitrate attenuated these detriments. In HFD-fed mice, FMT from HFD+Nitrate donors did not influence serum nitrate, blood pressure, adipose inflammation, or myocardial fibrosis. However, microbiota from HFD+Nitrate mice decreased serum lipids, LV ROS, and similar to FMT from LFD donors, prevented glucose intolerance and cardiac morphology changes. Therefore, the cardioprotective effects of nitrate are not dependent on reducing blood pressure, but rather mitigating gut dysbiosis, highlighting a nitrate-gut-heart axis.<br><br>ARTICLE HIGHLIGHTS: Identifying therapeutic approaches that prevent cardiometabolic diseases are clearly important, and nitrate represents one such potential compound given its multifactorial metabolic effects. We aimed to determine whether nitrate could prevent high-fat diet (HFD)-induced cardiac abnormalities and whether this was dependent on the gut microbiome. Dietary nitrate attenuated HFD-induced pathological changes in cardiac remodelling, left ventricle reactive oxygen species, adipose inflammation, lipid homeostasis, glucose intolerance, and gut dysbiosis. Fecal microbial transplantation from nitrate-fed mice also prevented serum dyslipidemia, left ventricle reactive oxygen species, glucose intolerance, and cardiac dysfunction. Therefore, the cardioprotective effects of nitrate are related to mitigating gut dysbiosis, highlighting a nitrate-gut-heart axis.}, }
@article {pmid36811017, year = {2023}, author = {Ralli, T and Saifi, Z and Rathee, A and Aeri, V and Kohli, K}, title = {Decoding the bidirectional relationship between gut microbiota and COVID-19.}, journal = {Heliyon}, volume = {9}, number = {3}, pages = {e13801}, pmid = {36811017}, issn = {2405-8440}, abstract = {From late 2019, whole world has been facing COVID-19 pandemic which is caused by SARS-CoV-2 virus. This virus primarily attacks the respiratory tract and enter host cell by binding with angiotensin 2 converting enzyme receptors present on alveoli of the lungs. Despite its binding in the lungs, many patients have reported gastrointestinal symptoms and indeed, RNA of the virus have been found in faecal sample of patients. This observation gave a clue of the involvement of gut-lung axis in this disease development and progression. From several studies reported in past two years, intestinal microbiome has shown to have bidirectional link with lungs i.e., gut dysbiosis increases the tendency of infection with COVID-19 and coronavirus can also cause perturbations in intestinal microbial composition. Thus, in this review we have tried to figure out the mechanisms by which disturbances in the gut composition can increase the susceptibility to COVID-19. Understanding these mechanisms can play a crucial role in decreasing the disease outcomes by manipulating the gut microbiome using prebiotics, probiotics, or combination of two. Even, faecal microbiota transplantation can also show better results, but intensive clinical trials need to be done first.}, }
@article {pmid36810253, year = {2023}, author = {Li, Z and Zhou, E and Liu, C and Wicks, H and Yildiz, S and Razack, F and Ying, Z and Kooijman, S and Koonen, DPY and Heijink, M and Kostidis, S and Giera, M and Sanders, IMJG and Kuijper, EJ and Smits, WK and van Dijk, KW and Rensen, PCN and Wang, Y}, title = {Dietary butyrate ameliorates metabolic health associated with selective proliferation of gut Lachnospiraceae bacterium 28-4.}, journal = {JCI insight}, volume = {8}, number = {4}, pages = {}, pmid = {36810253}, issn = {2379-3708}, mesh = {Humans ; Animals ; Mice ; *Butyrates/adverse effects ; Obesity/metabolism ; *Metabolic Syndrome ; RNA, Ribosomal, 16S ; Weight Gain ; Cell Proliferation ; }, abstract = {Short-chain fatty acids, including butyrate, have multiple metabolic benefits in individuals who are lean but not in individuals with metabolic syndrome, with the underlying mechanisms still being unclear. We aimed to investigate the role of gut microbiota in the induction of metabolic benefits of dietary butyrate. We performed antibiotic-induced microbiota depletion of the gut and fecal microbiota transplantation (FMT) in APOE*3-Leiden.CETP mice, a well-established translational model for developing human-like metabolic syndrome, and revealed that dietary butyrate reduced appetite and ameliorated high-fat diet-induced (HFD-induced) weight gain dependent on the presence of gut microbiota. FMT from butyrate-treated lean donor mice, but not butyrate-treated obese donor mice, into gut microbiota-depleted recipient mice reduced food intake, attenuated HFD-induced weight gain, and improved insulin resistance. 16S rRNA and metagenomic sequencing on cecal bacterial DNA of recipient mice implied that these effects were accompanied by the selective proliferation of Lachnospiraceae bacterium 28-4 in the gut as induced by butyrate. Collectively, our findings reveal a crucial role of gut microbiota in the beneficial metabolic effects of dietary butyrate as strongly associated with the abundance of Lachnospiraceae bacterium 28-4.}, }
@article {pmid36810115, year = {2023}, author = {Pan, W and Zhao, J and Wu, J and Xu, D and Meng, X and Jiang, P and Shi, H and Ge, X and Yang, X and Hu, M and Zhang, P and Tang, R and Nagaratnam, N and Zheng, K and Huang, XF and Yu, Y}, title = {Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {30}, pmid = {36810115}, issn = {2049-2618}, mesh = {Mice ; Animals ; *Diet, High-Fat ; Brain-Gut Axis ; Obesity/microbiology ; Propionates ; *Cognitive Dysfunction ; Cytokines/genetics ; Butyrates ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Gut homeostasis, including intestinal immunity and microbiome, is essential for cognitive function via the gut-brain axis. This axis is altered in high-fat diet (HFD)-induced cognitive impairment and is closely associated with neurodegenerative diseases. Dimethyl itaconate (DI) is an itaconate derivative and has recently attracted extensive interest due to its anti-inflammatory effect. This study investigated whether intraperitoneal administration of DI improves the gut-brain axis and prevents cognitive deficits in HF diet-fed mice.<br><br>RESULTS: DI effectively attenuated HFD-induced cognitive decline in behavioral tests of object location, novel object recognition, and nesting building, concurrent with the improvement of hippocampal RNA transcription profiles of genes associated with cognition and synaptic plasticity. In agreement, DI reduced the damage of synaptic ultrastructure and deficit of proteins (BDNF, SYN, and PSD95), the microglial activation, and neuroinflammation in the HFD-fed mice. In the colon, DI significantly lowered macrophage infiltration and the expression of pro-inflammatory cytokines (TNF-&#x3b1;, IL-1&#x3b2;, IL-6) in mice on the HF diet, while upregulating the expression of immune homeostasis-related cytokines (IL-22, IL-23) and antimicrobial peptide Reg3&#x3b3;. Moreover, DI alleviated HFD-induced gut barrier impairments, including elevation of colonic mucus thickness and expression of tight junction proteins (zonula occludens-1, occludin). Notably, HFD-induced microbiome alteration was improved by DI supplementation, characterized by the increase of propionate- and butyrate-producing bacteria. Correspondingly, DI increased the levels of propionate and butyrate in the serum of HFD mice. Intriguingly, fecal microbiome transplantation from DI-treated HF mice facilitated cognitive variables compared with HF mice, including higher cognitive indexes in behavior tests and optimization of hippocampal synaptic ultrastructure. These results highlight the gut microbiota is necessary for the effects of DI in improving cognitive impairment.<br><br>CONCLUSIONS: The present study provides the first evidence that DI improves cognition and brain function with significant beneficial effects via the gut-brain axis, suggesting that DI may serve as a novel drug for treating obesity-associated neurodegenerative diseases. Video Abstract.}, }
@article {pmid36809182, year = {2023}, author = {Olekhnovich, EI and Ivanov, AB and Babkina, AA and Sokolov, AA and Ulyantsev, VI and Fedorov, DE and Ilina, EN}, title = {Consistent Stool Metagenomic Biomarkers Associated with the Response To Melanoma Immunotherapy.}, journal = {mSystems}, volume = {8}, number = {2}, pages = {e0102322}, pmid = {36809182}, issn = {2379-5077}, mesh = {Humans ; Metagenome ; *Melanoma/genetics ; *Microbiota/genetics ; Bacteria/genetics ; Biomarkers ; Immunotherapy/methods ; }, abstract = {The human gut microbiome plays an important role in both health and disease. Recent studies have demonstrated a strong influence of the gut microbiome composition on the efficacy of cancer immunotherapy. However, available studies have not yet succeeded in finding reliable and consistent metagenomic markers that are associated with the response to immunotherapy. Therefore, the reanalysis of the published data may improve our understanding of the association between the composition of the gut microbiome and the treatment response. In this study, we focused on melanoma-related metagenomic data, which are more abundant than are data from other tumor types. We analyzed the metagenomes of 680 stool samples from 7 studies that were published earlier. The taxonomic and functional biomarkers were selected after comparing the metagenomes of patients showing different treatment responses. The list of selected biomarkers was also validated on additional metagenomic data sets that were dedicated to the influence of fecal microbiota transplantation on the response to melanoma immunotherapy. According to our analysis, the resulting cross-study taxonomic biomarkers included three bacterial species: Faecalibacterium prausnitzii, Bifidobacterium adolescentis, and Eubacterium rectale. 101 groups of genes were identified to be functional biomarkers, including those potentially involved in the production of immune-stimulating molecules and metabolites. Moreover, we ranked the microbial species by the number of genes encoding functionally relevant biomarkers that they contained. Thus, we put together a list of potentially the most beneficial bacteria for immunotherapy success. F. prausnitzii, E. rectale, and three species of bifidobacteria stood out as the most beneficial species, even though some useful functions were also present in other bacterial species. IMPORTANCE In this study, we put together a list of potentially the most beneficial bacteria that were associated with a responsiveness to melanoma immunotherapy. Another important result of this study is the list of functional biomarkers of responsiveness to immunotherapy, which are dispersed among different bacterial species. This result possibly explains the existing irregularities between studies regarding the bacterial species that are beneficial to melanoma immunotherapy. Overall, these findings can be utilized to issue recommendations for gut microbiome correction in cancer immunotherapy, and the resulting list of biomarkers might serve as a good stepping stone for the development of a diagnostic test that is aimed at predicting patients' responses to melanoma immunotherapy.}, }
@article {pmid36807754, year = {2023}, author = {Lindner, M and Radke, DI and Elke, G}, title = {[Bacterial gut microbiota-key player in sepsis].}, journal = {Medizinische Klinik, Intensivmedizin und Notfallmedizin}, volume = {118}, number = {2}, pages = {107-113}, pmid = {36807754}, issn = {2193-6226}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Bacteria ; *Sepsis ; Dysbiosis/complications/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiota is comprised of over 1200 different bacteria and forms a symbiotic community with the human organism, the holobiont. It plays an important role in the maintenance of homeostasis, e.g., of the immune system and essential metabolic processes. Disturbances in the balance of this reciprocal relationship are called dysbiosis and, in the field of sepsis, are associated with incidence of disease, extent of the systemic inflammatory response, severity of organ dysfunction, and mortality. In addition to providing guiding principles in the fascinating relationship between "human and microbe," this article summarizes recent findings regarding the role of the bacterial gut microbiota in sepsis, which is one a very relevant in intensive care medicine.}, }
@article {pmid36806616, year = {2023}, author = {Fortman, D and Avellan, MGP and Hurd, D and Schwartz, M and Dubner, H and Hewitt, C and Berton, S and Ernst, S and Rose, A and Zarour, HWH and Davar, D}, title = {Screening costs associated with donor selection for fecal microbiota transplantation for treatment of PD-1 refractory melanoma patients.}, journal = {Melanoma research}, volume = {33}, number = {2}, pages = {136-148}, pmid = {36806616}, issn = {1473-5636}, support = {R01 CA222203/CA/NCI NIH HHS/United States ; U01 CA268806/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; Donor Selection ; *Clostridioides difficile ; *Epstein-Barr Virus Infections/etiology ; Seroepidemiologic Studies ; SARS-CoV-2 ; *COVID-19 ; *Melanoma/etiology ; Herpesvirus 4, Human ; *Skin Neoplasms/etiology ; }, abstract = {The gut microbiome acts as a tumor-extrinsic regulator of responses to immune-checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors. Primary resistance to anti-PD-1 ICI can be reversed via responder-derived fecal microbiota transplant (FMT) in patients with refractory melanoma. Efforts to create stool banks for FMT have proved difficult. Therefore, we aimed to establish a novel donor-screening program to generate responder-derived FMT for use in PD-1 refractory melanoma. Candidate PD-1 responder donors and PD-1 refractory recipients were recruited via clinic-based encounters at the University of Pittsburgh Medical Center hospitals. Eligible donors and recipients underwent physician assessment and screening of serum, stool and nasopharynx for transmissible agents, which included SARS-CoV-2 modification. The cost of donor and recipient screening was calculated. Initially, 29 donors were screened with 14 eligible donors identified after exclusion; of the 14 donors, eight were utilized in clinical trials. The overall efficiency of screening was 48%. Seroprevalence rates for cytomegalovirus, Epstein-Barr virus, HSV-2, HHV-6, HTLV-1, HTLV-2, and syphilis were similar to published statistics from healthy blood donors in the USA. Donor stool studies indicated a 3.6% incidence of E. histolytica and norovirus, 3.7% incidence of giardia and 7.1% incidence of C. difficile. A single donor tested positive for SARS-CoV-2 in stool only. The cost for finding a single eligible donor was $2260.24 (pre-COVID) and $2,460.24 (post-COVID). The observed screening efficiency suggests that a well-resourced screening program can generate sufficient responder-derived donor material for clinical trial purposes. Eliminating testing for low-prevalence organisms may improve cost-effectiveness.}, }
@article {pmid36805882, year = {2023}, author = {Grosen, AK and Mikkelsen, S and Baunwall, SMD and Dahlerup, JF and Erikstrup, LT and Hvas, CL and Erikstrup, C}, title = {Risk of Helicobacter pylori transmission by faecal microbiota transplantation via oral capsules.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {29}, number = {6}, pages = {799.e1-799.e4}, doi = {10.1016/j.cmi.2023.02.011}, pmid = {36805882}, issn = {1469-0691}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Helicobacter pylori ; Retrospective Studies ; Feces/microbiology ; Tissue Donors ; }, abstract = {OBJECTIVES: The aim was to determine if Helicobacter pylori is transmitted from donors to recipients by faecal microbiota transplantation (FMT) via oral capsules.<br><br>METHODS: In a cohort of faeces donors not primarily screened for H.&#xa0;pylori, consecutive stool samples were retrospectively analysed by the H.&#xa0;pylori stool antigen test (SAT). Subsequently, we analysed recipient stool samples collected before and after receiving faeces donated by H.&#xa0;pylori SAT-positive donors, and we recorded recipient use of antibiotics and proton pump inhibitors. All stool samples were frozen upon collection and stored at&#xa0;-80&#xb0;C until use.<br><br>RESULTS: Thirteen out of 40 faeces donors (33%; 95% CI, 20-48%) were H.&#xa0;pylori SAT-positive. Among those positive, five donors donated faeces for 28 capsule-based FMTs performed in 26 recipients with stool samples collected before and after FMT. At a median of 59&#xa0;days (range, 7-84&#xa0;days) after FMT, no recipients (0%; 95% CI, 0-11%) were H.&#xa0;pylori SAT-positive.<br><br>DISCUSSION: We found no occurrence of H.&#xa0;pylori transmission from healthy, asymptomatic donors to recipients by oral capsule-based FMT, although with a wide CI.}, }
@article {pmid36805186, year = {2023}, author = {Liu, N and Liu, J and Zheng, B and Zeng, X and Ye, Z and Huang, X and Liu, W and Liu, Y and Fang, Q and Chen, L and Rao, T and Ouyang, D}, title = {Gut microbiota affects sensitivity to immune-mediated isoniazid-induced liver injury.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {160}, number = {}, pages = {114400}, doi = {10.1016/j.biopha.2023.114400}, pmid = {36805186}, issn = {1950-6007}, mesh = {Mice ; Animals ; Isoniazid/toxicity ; *Gastrointestinal Microbiome ; *Chemical and Drug Induced Liver Injury, Chronic ; Antitubercular Agents/toxicity ; *Chemical and Drug Induced Liver Injury ; Liver ; }, abstract = {Isoniazid (INH) is a highly effective single and/or combined first-line anti-tuberculosis (anti-TB) therapy drug, and the hepatotoxicity greatly limits its clinical application. INH-induced liver injury (INH-DILI) is a typical immune-mediated idiosyncratic drug-induced liver injury. Existing mechanisms including genetic variations in drug metabolism and immune responses cannot fully explain the differences in susceptibility and sensitivity to INH-DILI, suggesting that other factors may be involved. Accumulating evidence indicates that the development and severity of immune-mediated liver injury is related to gut microbiota. In this study, INH exposure caused liver damage, immune disregulation and microbiota profile alteration. Depletion of gut microbiota ameliorated INH-DILI, and improved INH-DILI-associated immune disorder and inflammatory response. Moreover, hepatotoxicity of INH was ameliorated by fecal microbiota transplantation (FMT) from INH-treated mice. Notably, Bifidobacterium abundance was significantly associated with transaminase levels. In conclusion, our results suggested that the effect of gut microbiota on INH-DILI was related to immunity, and the difference in INH-DILI sensitivity was related to the structure of gut microbiota. Changes in the structure of gut microbiota by continuous exposure of INH resulted in the tolerance to liver injury, and probiotics such as Bifidobacterium might play an important role in INH-DILI and its "adaptation" phenomenon. This work provides novel evidence for elucidating the underlying mechanism of difference in individual's response to INH-DILI and potential approach for intervening anti-TB drug liver injury by modulating gut microbiota.}, }
@article {pmid36805016, year = {2023}, author = {Donskey, CJ}, title = {Update on Clostridioides difficile Infection in Older Adults.}, journal = {Infectious disease clinics of North America}, volume = {37}, number = {1}, pages = {87-102}, doi = {10.1016/j.idc.2022.10.001}, pmid = {36805016}, issn = {1557-9824}, mesh = {Humans ; Aged ; *Clostridioides difficile ; Quality of Life ; *Clostridium Infections/diagnosis/drug therapy/epidemiology ; *Cross Infection/diagnosis/epidemiology ; Health Facilities ; }, abstract = {Clostridioides difficile is a common cause of community-associated and health care-associated infections. Older adults are disproportionately affected, and long-term care facilities (LTCFs) have borne a substantial proportion of the burden of C difficile infection (CDI). Recurrences of CDI are common in older adults and have substantial adverse effects on quality of life. Appropriate diagnostic testing and management is essential for older adults in the community and in LTCFs. This review focuses on current concepts related to the epidemiology, diagnosis, and management of CDI in older adults.}, }
@article {pmid36803643, year = {2023}, author = {Devolder, L and Pauwels, A and Van Remoortel, A and Falony, G and Vieira-Silva, S and Nagels, G and De Keyser, J and Raes, J and D'Hooghe, MB}, title = {Gut microbiome composition is associated with long-term disability worsening in multiple sclerosis.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2180316}, pmid = {36803643}, issn = {1949-0984}, mesh = {Humans ; *Multiple Sclerosis ; *Gastrointestinal Microbiome ; }, abstract = {Predicting the long-term outcome of multiple sclerosis (MS) remains an important challenge to this day. As the gut microbiota is emerging as a potential player in MS, we investigated in this study whether gut microbial composition at baseline is related to long-term disability worsening in a longitudinal cohort of 111 MS patients. Fecal samples and extensive host metadata were collected at baseline and 3 months post-baseline, with additional repeated neurological measurements performed over (median) 4.4 y. Worsening (with EDSS-Plus) occurred in 39/95 patients (outcome undetermined for 16 individuals). The inflammation-associated, dysbiotic Bacteroides 2 enterotype (Bact2) was detected at baseline in 43.6% of worsened patients, while only 16.1% of non-worsened patients harbored Bact2. This association was independent of identified confounders, and Bact2 was more strongly associated with EDSS-Plus than neurofilament light chain (NfL) plasma levels. Furthermore, using fecal sampling performed 3 months post-baseline, we observed Bact2 to be relatively stable, suggesting its potential use as a prognostic biomarker in MS clinical practice.}, }
@article {pmid36803386, year = {2023}, author = {Wang, Y and He, Y and Liang, Y and Liu, H and Chen, X and Kulyar, MF and Shahzad, A and Wei, K and Li, K}, title = {Fecal microbiota transplantation attenuates Escherichia coli infected outgrowth by modulating the intestinal microbiome.}, journal = {Microbial cell factories}, volume = {22}, number = {1}, pages = {30}, pmid = {36803386}, issn = {1475-2859}, support = {GuiKeAA18242040//Guangxi Science and Technology Project/ ; 804131//Start-up fund of Nanjing Agricultural University/ ; 80900219//Start-up Fund for Distinguished Scholars of Nanjing Agricultural Universitry/ ; }, mesh = {Humans ; Animals ; Mice ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Escherichia coli ; Feces/microbiology ; *Microbiota ; }, abstract = {BACKGROUND: Given the crucial role of gut microbiota in animal and human health, studies on modulating the intestinal microbiome for therapeutic purposes have grasped a significant attention, of which the role of fecal microbiota transplantation (FMT) has been emphasized.<br><br>METHODS: In the current study, we evaluated the effect of FMT on gut functions in Escherichia coli (E. coli) infection&#xa0;by using mice model. Moreover, we&#xa0;also investigated the subsequently dependent variables of infection, i.e., body weight, mortality, intestinal histopathology, and the expression&#xa0;changes in tight junction proteins (TJPs).<br><br>RESULTS: The FMT effectively decreased weight loss and mortality to a certain extent&#xa0;with the restoration of&#xa0;intestinal villi that resulted in high histological scores for jejunum tissue damage (p&#x2009;<&#x2009;0.05). The effect of FMT on alleviating the reduction of intestinal TJPs was also proved by immunohistochemistry analysis and mRNA expression levels.&#xa0;Moreover, the abundance of health-threatening bacteria, belonging to phylum Proteobacteria, family Enterobacteriaceae&#xa0;and Tannerellaceae, genus Escherichia-Shigella, Sphingomonas, Collinsella, etc., were significantly increased, whereas beneficial bacteria, belonging to&#xa0;phylum Firmicutes, family Lactobacillaceae, genus Lactobacillus&#xa0;were decreased in the gut of infected mice. Furthermore, we sought to investigate the association of clinical symptoms with FMT treatment with modulation in gut microbiota. According to beta diversity, the microbial community&#xa0;of gut microbiota results reflected the similarities between non-infected and FMT groups. The improvement of the intestinal microbiota in FMT&#xa0;group was characterized by the significant high level of beneficial microorganisms with the&#xa0;synergistic decrease of Escherichia-Shigella, Acinetobacter, and other taxa.<br><br>CONCLUSION: The findings suggest a beneficial host-microbiome correlation following fecal microbiota transplanatation&#xa0;for controlling gut infections and pathogens-associated diseases.}, }
@article {pmid36803092, year = {2024}, author = {Wang, C and Bai, J and Chen, X and Song, J and Zhang, Y and Wang, H and Suo, H}, title = {Gut microbiome-based strategies for host health and disease.}, journal = {Critical reviews in food science and nutrition}, volume = {64}, number = {19}, pages = {6834-6849}, doi = {10.1080/10408398.2023.2176464}, pmid = {36803092}, issn = {1549-7852}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Probiotics ; *Prebiotics ; *Fecal Microbiota Transplantation/methods ; *Diet ; Anti-Bacterial Agents/pharmacology ; Bacteriophages/physiology ; }, abstract = {Host health and disease are influenced by changes in the abundance and structure of intestinal flora. Current strategies are focused on regulating the structure of intestinal flora to ensure host health by alleviating disease. However, these strategies are limited by multiple factors, such as host genotype, physiology (microbiome, immunity, and gender), intervention, and diet. Accordingly, we reviewed the prospects and limitations of all strategies regulating the structure and abundance of microflora, including probiotics, prebiotics, diet, fecal microbiota transplantation, antibiotics, and phages. Some new technologies that can improve these strategies are also introduced. Compared with other strategies, diets and prebiotics are associated with reduced risk and high security. Besides, phages have the potential for application in the targeted regulation of intestinal microbiota due to their high specificity. Notably, the variability in individual microflora and their metabolic response to different interventions should be considered. Future studies should use artificial intelligence combined with multi-omics to investigate the host genome and physiology based on factors, such as blood type, dietary habits, and exercise, in order to develop individualized intervention strategies to improve host health.}, }
@article {pmid36800331, year = {2023}, author = {Shafique, I and Andleeb, S and Naeem, F and Ali, S and Tabassam, T and Sultan, T and Almas Abbasi, M}, title = {Cow dung putrefaction via vermicomposting using Eisenia fetida and its influence on seed sprouting and vegetative growth of Viola wittrockiana (pansy).}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0279828}, pmid = {36800331}, issn = {1932-6203}, mesh = {Animals ; Female ; Cattle ; *Viola ; *Oligochaeta ; Feces/chemistry ; Seeds ; Manure/analysis ; Soil ; }, abstract = {The current research was conducted at Vermi-tech Unit, Muzaffarabad in 2018 to evaluate the efficacy of cow dung and vermicompost on seed sprouting, seedlings, and vegetative developmental parameters of Viola x wittrokiana (pansy). In the current study, vermicompost was produced using Eisenia fetida. Physicochemical parameters of vermicompost and organic manure were recorded before each experimentation. The potting experiment was designed and comprised of eight germination mediums containing different combinations of soil, sand, cow dung, and various concentrations of vermicompost such as 10% VC, 15% VC, 20% VC, 25% VC, 30% VC, and 35% VC. Seed sprouting and seedling developmental parameters were observed for 28 days while vegetative plant growth parameters were recorded after 10 weeks of transplantation in various vermicompost amended germination media. Pre and post-physicochemical analysis of germination media were also recorded to check their quality and permanency. The current findings showed that 30% VC germination media was an effective dose for early seed germination initiation and all seed germination parameters. However, the significant vegetative plant growth and flowering parameters of pansy occurred at 35% VC. Findings revealed that vermicompost not only enhanced the seed germination and growth of pansy but also improved soil health. These results indicate that vermicompost can be exploited as a potent bio-fertilizer for ornamental plant production.}, }
@article {pmid36799251, year = {2023}, author = {Rector, A and Bloemen, M and Thijssen, M and Delang, L and Raymenants, J and Thibaut, J and Pussig, B and Fondu, L and Aertgeerts, B and Van Ranst, M and Van Geet, C and Arnout, J and Wollants, E}, title = {Monitoring of SARS-CoV-2 concentration and circulation of variants of concern in wastewater of Leuven, Belgium.}, journal = {Journal of medical virology}, volume = {95}, number = {2}, pages = {e28587}, doi = {10.1002/jmv.28587}, pmid = {36799251}, issn = {1096-9071}, mesh = {Humans ; *SARS-CoV-2 ; Belgium ; *COVID-19 ; Wastewater ; Wastewater-Based Epidemiological Monitoring ; RNA, Viral ; }, abstract = {Wastewater surveillance plays an important role in the management of the coronavirus disease 2019 (COVID-19) pandemic all over the world. Using different wastewater collection points in Leuven, we wanted to investigate the use of wastewater surveillance as an early warning system for an uprise of infections and as a tool to follow the circulation of specific variants of concern (VOCs) in particular geographic areas. Wastewater samples were collected from local neighborhood sewers and from a large regional wastewater treatment plant (WWTP) in the area of Leuven, Belgium. After virus concentration, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was quantified by real-time quantitative polymerase chain reaction (RT-qPCR) and normalized with the human fecal indicator pepper mild mottle virus (PMMoV). A combination of multiplex RT-qPCR assays was used to detect signature mutations of circulating VOCs. Fecal virus shedding of SARS-CoV-2 variants was measured in feces samples of hospitalized patients. In two residential sampling sites, a rise in wastewater SARS-CoV-2 concentration preceded peaks in positive cases. In the WWTP, viral load peaks were seen concomitant with the consecutive waves of positive cases caused by the original Wuhan SARS-CoV-2 strain and subsequent VOCs. During the Omicron BA.1 wave, the wastewater viral load increased to a lesser degree, even after normalization of SARS-CoV-2 concentration using PMMoV. This might be attributable to a lower level of fecal excretion of this variant. Circulation of SARS-CoV-2 VOCs Alpha, Delta, Omicron BA1/BA.2, and BA.4/BA.5 could be detected based on the presence of specific key mutations. The shift in variants was noticeable in the wastewater, with key mutations of two different variants being present simultaneously during the transition period. Wastewater-based surveillance is a sensitive tool to monitor SARS-CoV-2 circulation levels and VOCs in larger regions. In times of reduced test capacity, this can prove to be highly valuable. Differences in excretion levels of various SARS-CoV-2 variants should however be taken into account when using wastewater surveillance to monitor SARS-CoV-2 circulation levels in the population.}, }
@article {pmid36798129, year = {2023}, author = {Yuan, H and Gui, R and Wang, Z and Fang, F and Zhao, H}, title = {Gut microbiota: A novel and potential target for radioimmunotherapy in colorectal cancer.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1128774}, pmid = {36798129}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Radioimmunotherapy/adverse effects ; *Carcinoma, Non-Small-Cell Lung/complications ; *Lung Neoplasms/complications ; *Colorectal Neoplasms/radiotherapy/metabolism ; }, abstract = {Colorectal cancer (CRC) is one of the most common cancers, with a high mortality rate, and is a major burden on human health worldwide. Gut microbiota regulate human immunity and metabolism through producing numerous metabolites, which act as signaling molecules and substrates for metabolic reactions in various biological processes. The importance of host-gut microbiota interactions in immunometabolic mechanisms in CRC is increasingly recognized, and interest in modulating the microbiota to improve patient's response to therapy has been raising. However, the specific mechanisms by which gut microbiota interact with immunotherapy and radiotherapy remain incongruent. Here we review recent advances and discuss the feasibility of gut microbiota as a regulatory target to enhance the immunogenicity of CRC, improve the radiosensitivity of colorectal tumor cells and ameliorate complications such as radiotoxicity. Currently, great breakthroughs in the treatment of non-small cell lung cancer and others have been achieved by radioimmunotherapy, but radioimmunotherapy alone has not been effective in CRC patients. By summarizing the recent preclinical and clinical evidence and considering regulatory roles played by microflora in the gut, such as anti-tumor immunity, we discuss the potential of targeting gut microbiota to enhance the efficacy of radioimmunotherapy in CRC and expect this review can provide references and fresh ideas for the clinical application of this novel strategy.}, }
@article {pmid36796501, year = {2023}, author = {Wang, R and Jiang, C and Wu, Z and Wang, Z and Peng, Y and Li, Z and Zhang, Z and Lin, H and Chen, Z}, title = {Fecal Microbiota Transplantation Revealed a Pain-related Gut Microbiota Community in Ovariectomized Mice.}, journal = {The journal of pain}, volume = {24}, number = {7}, pages = {1203-1212}, doi = {10.1016/j.jpain.2023.02.003}, pmid = {36796501}, issn = {1528-8447}, mesh = {Female ; Mice ; Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Hyperalgesia/therapy ; RNA, Ribosomal, 16S/genetics ; Pain ; }, abstract = {Higher sensitivity to pain is a common clinical symptom in postmenopausal females. The gut microbiota (GM) has recently been identified as participating in various pathophysiological processes and may change during menopause and contribute to multiple postmenopausal symptoms. Here, we investigated the possible correlation between GM alteration and allodynia in ovariectomized (OVX) mice. Results showed that OVX mice exhibited allodynia from 7 weeks after surgery compared with sham-operated (SHAM) mice by comparing pain-related behaviors. Fecal microbiota transplantation (FMT) from OVX mice induced allodynia in normal mice while FMT from SHAM mice alleviated allodynia in OVX mice. Microbiome 16S rRNA sequencing and linear discriminant analysis revealed alteration of the GM after OVX. Furthermore, Spearman's correlation analysis showed associations between pain-related behaviors and genera, and further verification identified the possible pain-related genera complex. Our findings provide new insights into the underlying mechanisms of postmenopausal allodynia, and suggest pain-related microbiota community as a promising therapeutic target. PERSPECTIVE: This article provided the evidence of gut microbiota playing essential roles in postmenopausal allodynia. This work intended to offer a guidance for further mechanism investigation into gut-brain axis and probiotics screening for postmenopausal chronic pain.}, }
@article {pmid36794804, year = {2023}, author = {Kurt, F and Leventhal, GE and Spalinger, MR and Anthamatten, L and Rogalla von Bieberstein, P and Menzi, C and Reichlin, M and Meola, M and Rosenthal, F and Rogler, G and Lacroix, C and de Wouters, T}, title = {Co-cultivation is a powerful approach to produce a robust functionally designed synthetic consortium as a live biotherapeutic product (LBP).}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2177486}, pmid = {36794804}, issn = {1949-0984}, mesh = {Mice ; Animals ; Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Colitis/therapy ; Feces/microbiology ; *Microbiota ; }, abstract = {The success of fecal microbiota transplants (FMT) has provided the necessary proof-of-concept for microbiome therapeutics. Yet, feces-based therapies have many associated risks and uncertainties, and hence defined microbial consortia that modify the microbiome in a targeted manner have emerged as a promising safer alternative to FMT. The development of such live biotherapeutic products has important challenges, including the selection of appropriate strains and the controlled production of the consortia at scale. Here, we report on an ecology- and biotechnology-based approach to microbial consortium construction that overcomes these issues. We selected nine strains that form a consortium to emulate the central metabolic pathways of carbohydrate fermentation in the healthy human gut microbiota. Continuous co-culturing of the bacteria produces a stable and reproducible consortium whose growth and metabolic activity are distinct from an equivalent mix of individually cultured strains. Further, we showed that our function-based consortium is as effective as FMT in counteracting dysbiosis in a dextran sodium sulfate mouse model of acute colitis, while an equivalent mix of strains failed to match FMT. Finally, we showed robustness and general applicability of our approach by designing and producing additional stable consortia of controlled composition. We propose that combining a bottom-up functional design with continuous co-cultivation is a powerful strategy to produce robust functionally designed synthetic consortia for therapeutic use.}, }
@article {pmid36794690, year = {2023}, author = {Carnero, EA and Bock, CP and Liu, Y and Corbin, K and Wohlers-Kariesch, E and Ruud, K and Moon, J and Marcus, A and Krajmalnik-Brown, R and Muraviev, A and Vodopyanov, KL and Smith, SR}, title = {Measurement of 24-h continuous human CH4 release in a whole room indirect calorimeter.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {134}, number = {3}, pages = {766-776}, pmid = {36794690}, issn = {1522-1601}, support = {R01 DK105829/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Reproducibility of Results ; *Energy Metabolism ; *Diet ; Energy Intake ; Intestines ; }, abstract = {We describe the technology and validation of a new whole room indirect calorimeter (WRIC) methodology to quantify volume of methane (VCH4) released from the human body over 24 h concurrently with the assessment of energy expenditure and substrate utilization. The new system extends the assessment of energy metabolism by adding CH4, a downstream product of microbiome fermentation that could contribute to energy balance. Our new system consists of an established WRIC combined with the addition of off-axis integrated-cavity output spectroscopy (OA-ICOS) to measure CH4 concentration ([CH4]). Development, validation, and reliability of the system included environmental experiments to measure the stability of the atmospheric [CH4], infusing CH4 into the WRIC and human cross-validation studies comparing [CH4] quantified by OA-ICOS and mid-infrared dual-comb spectroscopy (MIR DCS).Our infusion data indicated that the system measured 24-h [CH4] and VCH4 with high sensitivity, reliability, and validity. Cross-validation studies showed good agreement between OA-ICOS and MIR DCS technologies (r = 0.979, P < 0.0001). Human data revealed 24-h VCH4 was highly variable between subjects and within/between days. Finally, our method to quantify VCH4 released by breath or colon suggested that over 50% of the CH4 was eliminated through the breath. The method allows, for the first time, measurement of 24-h VCH4 (in kcal) and therefore the measurement of the proportion of human energy intake fermented to CH4 by the gut microbiome and released via breath or from the intestine; also, it allows us to track the effects of dietary, probiotic, bacterial, and fecal microbiota transplantation on VCH4.NEW &amp; NOTEWORTHY This is the first time that continuous assessment of CH4 is reported in parallel with measurements of O2 consumption and CO2 production inside a whole room indirect calorimeter in humans and over 24 h. We provide a detailed description of the whole system and its parts. We carried out studies of reliability and validity of the whole system and its parts. CH4 is released in humans during daily activities.}, }
@article {pmid36794370, year = {2023}, author = {van Lier, YF and Vos, J and Blom, B and Hazenberg, MD}, title = {Allogeneic hematopoietic cell transplantation, the microbiome, and graft-versus-host disease.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2178805}, pmid = {36794370}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/etiology ; *Microbiota ; Gastrointestinal Tract ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; }, abstract = {Many patients with hematological malignancies, such as acute myeloid leukemia, receive an allogeneic hematopoietic cell transplantation (HCT) to cure their underlying condition. Allogeneic HCT recipients are exposed to various elements during the pre-, peri- and post-transplant period that can disrupt intestinal microbiota, including chemo- and radiotherapy, antibiotics, and dietary changes. The dysbiotic post-HCT microbiome is characterized by low fecal microbial diversity, loss of anaerobic commensals, and intestinal domination, particularly by Enterococcus species, and is associated with poor transplant outcomes. Graft-versus-host disease (GvHD) is a frequent complication of allogeneic HCT caused by immunologic disparity between donor and host cells and results in tissue damage and inflammation. Microbiota injury is particularly pronounced in allogeneic HCT recipients who go on to develop GvHD. At present, manipulation of the microbiome for example, via dietary interventions, antibiotic stewardship, prebiotics, probiotics, or fecal microbiota transplantation, is widely being explored to prevent or treat gastrointestinal GvHD. This review discusses current insights into the role of the microbiome in GvHD pathogenesis and summarizes interventions to prevent and treat microbiota injury.}, }
@article {pmid36793054, year = {2023}, author = {Li, J and Huang, H and Fan, R and Hua, Y and Ma, W}, title = {Lipidomic analysis of brain and hippocampus from mice fed with high-fat diet and treated with fecal microbiota transplantation.}, journal = {Nutrition &amp; metabolism}, volume = {20}, number = {1}, pages = {12}, pmid = {36793054}, issn = {1743-7075}, abstract = {BACKGROUND: Dietary fat intake affects brain composition and function. Different types of dietary fatty acids alter species and abundance of brain lipids in mice. The aim of this study is to explore whether the changes are effective through gut microbiota.<br><br>METHODS: In our study, 8-week-old male C57BL/6 mice were randomly divided into 7 groups and fed with high-fat diet (HFD) with different fatty acid compositions, control (CON) group, long-chain saturated fatty acid (LCSFA) group, medium-chain saturated fatty acid (MCSFA) group, n-3 polyunsaturated fatty acid (n-3 PUFA) group, n-6 polyunsaturated fatty acid (n-6 PUFA) group, monounsaturated fatty acid (MUFA) group and trans fatty acid (TFA) group. Then, the fecal microbiota transplant (FMT) was performed in other pseudo germ-free mice after antibiotic treatment. The experimental groups were orally perfused with gut microbiota that induced by HFD with different types of dietary fatty acids. The mice were fed with regular fodder before and after FMT. High-performance liquid chromatography-mass spectrometry (LC-MS) was used to analysis the composition of fatty acids in the brain of HFD-fed mice and hippocampus of mice treated with FMT which was collected from HFD-fed mice.<br><br>RESULTS: The content of acyl-carnitines (AcCa) increased and lysophosphatidylgylcerol (LPG) decreased in all kinds of HFD groups. phosphatidic acids (PA), phosphatidylethanolamine (PE) and sphingomyelin (SM) contents were significantly increased in the n-6 PUFA-fed HFD group. The HFD elevated the saturation of brain fatty acyl (FA). Lysophosphatidylcholine (LPC), lysodi-methylphosphatidylethanolamine (LdMePE), monolysocardiolipin (MLCL), dihexosylceramides (Hex2Cer), and wax ester (WE) significantly increased after LCSFA-fed FMT. MLCL reduced and cardiolipin (CL) raised significantly after n-3 PUFA-fed FMT.<br><br>CONCLUSIONS: The study revealed, HFD and FMT in mice had certain effects on the content and composition of fatty acids in the brain, especially on glycerol phospholipid (GP). The change of AcCa content in FA was a good indicator of dietary fatty acid intake. By altering the fecal microbiota, dietary fatty acids might affect brain lipids.}, }
@article {pmid36791303, year = {2022}, author = {Beneš, J and Stebel, R and Musil, V and Krůtová, M and Vejmelka, J and Kohout, P}, title = {[Updated Czech guidelines for the treatment of patients with colitis due to Clostridioides difficile].}, journal = {Klinicka mikrobiologie a infekcni lekarstvi}, volume = {28}, number = {3}, pages = {77-94}, pmid = {36791303}, issn = {1211-264X}, mesh = {Humans ; Vancomycin/therapeutic use ; Fidaxomicin/therapeutic use ; *Clostridioides difficile ; Clostridioides ; Tigecycline/therapeutic use ; Czech Republic ; Aminoglycosides/adverse effects ; *Clostridium Infections/drug therapy ; Anti-Bacterial Agents/therapeutic use ; *Colitis/chemically induced/drug therapy ; }, abstract = {The updated Czech guidelines differ in some aspects from the 2021 guidelines issued by the ESCMID Study Group for Clostridium difficile. The key points of these Czech recommendations may be summarized as follows: • The drug of choice for hospitalized patients is orally administered fidaxomicin or vancomycin. In outpatients with a mild first episode of C. difficile infection, metronidazole can also be used. • If the patient's response to treatment is good and there are no complications, the duration of antibiotic treatment can be reduced (e.g. to 5 days in case of fidaxomicin or to 6-7 days in case of vancomycin). • If oral therapy is impossible, the drug of choice is tigecycline, 100 mg i.v., b.i.d., with initial shortening of the interval between the first and second doses for faster saturation. If the severity of the disease progresses during this antibiotic treatment, it is necessary to access the ileum or cecum, i.e. to perform double ileostomy or percutaneous endoscopic cecostomy, and to instill vancomycin or fidaxomicin lavages. • Fulminant C. difficile colitis should be treated with oral fidaxomicin ± tigecycline i.v. If peristalsis ceases, fidaxomicin should be administered into the ileum or cecum as described above. If sepsis develops, a broad-spectrum beta-lactam antibiotic (piperacillin/tazobactam, carbapenem) i.v. is added to topically administered fidaxomicin instead of tigecycline i.v.; at the same time, colectomy should be considered as the last resort. • To treat first recurrence, fidaxomicin or vancomycin is administered with a subsequent fecal microbiota transplant (FMT) from a healthy donor. For second or subsequent recurrence, administration of fidaxomicin is of little benefit; the therapy of choice is oral vancomycin and subsequent FMT. Prolonged vancomycin or fidaxomicin taper and pulse treatment is appropriate only when FMT cannot be performed.}, }
@article {pmid36788674, year = {2023}, author = {Han, B and Zhang, X and Wang, L and Yuan, W}, title = {Dysbiosis of Gut Microbiota Contributes to Uremic Cardiomyopathy via Induction of IFNγ-Producing CD4[+] T Cells Expansion.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0310122}, pmid = {36788674}, issn = {2165-0497}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/genetics ; Dysbiosis/therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; Case-Control Studies ; *Renal Insufficiency, Chronic/drug therapy/microbiology ; Interferon-gamma ; *Cardiomyopathies/therapy ; CD4-Positive T-Lymphocytes ; }, abstract = {Uremic cardiomyopathy (UCM) correlates with chronic kidney disease (CKD)-induced morbidity and mortality. Gut microbiota has been involved in the pathogenesis of certain cardiovascular disease, but the role of gut microbiota in the pathogenesis of UCM remains unknown. Here, we performed a case-control study to compare the gut microbiota of patients with CKD and healthy controls by 16S rRNA (rRNA) gene sequencing. To test the causative relationship between gut microbiota and UCM, we performed fecal microbiota transplantation (FMT) in 5/6th nephrectomy model of CKD. We found that opportunistic pathogens, particularly Klebsiella pneumoniae (K. pneumoniae), are markedly enriched in patients with CKD. FMT from CKD patients aggravated diastolic dysfunction in the mouse model. The diastolic dysfunction was associated with microbiome-dependent increases in heart-infiltrating IFNγ[+] CD4[+] T cells. Monocolonization with K. pneumoniae increased cardiac IFNγ[+] CD4[+] T cells infiltration and promoted UCM development of the mouse model. A probiotic Bifidobacterium animalis decreased the relative abundance of K. pneumoniae, reduced levels of cardiac IFNγ[+] CD4[+] T cells and ameliorated the severity of diastolic dysfunction in the mice. Thus, the aberrant gut microbiota in CKD patients, especially K. pneumoniae, contributed to UCM pathogenesis through the induction of heart-infiltrating IFNγ[+] CD4[+] T cells expansion, proposing that a Gut Microbiota-Gut-Kidney-Heart axis could play a critical role in elucidating the etiology of UCM, and suggesting that modulation of the gut bacteria may serve as a promising target for the amelioration of UCM. IMPORTANCE Uremic cardiomyopathy (UCM) correlates tightly with increased mortality in patients with chronic kidney disease (CKD), yet the pathogenesis of UCM remains incompletely understood, limiting therapeutic approaches. Our study proposed that a Gut Microbiota-Gut-Kidney-Heart axis could play a critical role in understanding etiology of UCM. There is a major need in future clinical trials of patients with CKD to explore if modulation of gut microbiota by fecal microbiota transplantation (FMT), probiotics or antibiotics can alleviate cardiac dysfunction, reduce mortality, and improve life quality.}, }
@article {pmid36788638, year = {2023}, author = {Pottenger, S and Watts, A and Wedley, A and Jopson, S and Darby, AC and Wigley, P}, title = {Timing and delivery route effects of cecal microbiome transplants on Salmonella Typhimurium infections in chickens: potential for in-hatchery delivery of microbial interventions.}, journal = {Animal microbiome}, volume = {5}, number = {1}, pages = {11}, pmid = {36788638}, issn = {2524-4671}, support = {BB/R008914/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Exposure to microbes early in life has long-lasting effects on microbial community structure and function of the microbiome. However, in commercial poultry settings chicks are reared as a single-age cohort with no exposure to adult birds which can have profound effects on microbiota development and subsequent pathogen challenge. Microbiota manipulation is a proven and promising strategy to help reduce pathogen load and transmission within broiler flocks. However, administration of microbiota transplant products in a hatchery setting may prove challenging. Effective administration strategies are dependent on key factors, such as; the age of chicks receiving interventions and mode of delivery. This study aimed to assess these two aspects to provide supporting evidence towards microbiome manipulation strategies for use in commercial hatcheries.<br><br>RESULTS: Manipulation of the microbiota between 4 and 72&#xa0;h of hatch markedly reduced faecal shedding and colonisation with the foodborne pathogen Salmonella enterica serovar Typhimurium (ST4/74). Administration of transplant material via spray or gel drop delivery systems had minimal effect on the protection conferred with fewer birds in transplant groups shown to shed ST4/74 in the faeces compared to PBS-gavaged control birds. Analysis of the microbiome following transplantation demonstrated that all transplant groups had higher diversity and species richness than non-transplant groups during the first week of life and the early stages of infection with ST47/4.The relative abundance of the bacterium Faecalibacterium prausnitzii was significantly higher in CMT groups compared to PBS controls. The presence of F. prausnitzii was also shown to increase in PBS-challenged birds compared to unchallenged birds potentially indicating a role of this bacterium in limiting Salmonella infections.<br><br>CONCLUSIONS: This study demonstrated that administration of microbiome transplants, using methods that would align with hatchery practices, effectively reduced colonisation and shedding of Salmonella in chickens. Age of chicks at microbiome administration had limited effect on the diversity and composition of the microbiome and conferred protection against Salmonella infections. Traditional hatchery delivery systems, such as spray or gel-drop, are sufficient to transfer donor material, alter the microbiome and confer protection against Salmonella. This study helps highlight the opportunity for use of microbiome modification methods within the hatchery.}, }
@article {pmid36786456, year = {2023}, author = {Chauhan, A and Garg, M}, title = {Editorial: faecal microbiota transplantation for recurrent C. difficile infections-getting the support that is needed.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {57}, number = {5}, pages = {585-586}, doi = {10.1111/apt.17341}, pmid = {36786456}, issn = {1365-2036}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridioides difficile ; Feces ; *Clostridium Infections/therapy ; }, }
@article {pmid36781906, year = {2023}, author = {Jeon, JH and Kaiser, EE and Waters, ES and Yang, X and Lourenco, JM and Fagan, MM and Scheulin, KM and Sneed, SE and Shin, SK and Kinder, HA and Kumar, A and Platt, SR and Ahn, J and Duberstein, KJ and Rothrock, MJ and Callaway, TR and Xie, J and West, FD and Park, HJ}, title = {Tanshinone IIA-loaded nanoparticles and neural stem cell combination therapy improves gut homeostasis and recovery in a pig ischemic stroke model.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2520}, pmid = {36781906}, issn = {2045-2322}, support = {R01 CA247769/CA/NCI NIH HHS/United States ; R01 CA257851/CA/NCI NIH HHS/United States ; R01 NS093314/NS/NINDS NIH HHS/United States ; R01NS093314/NS/NINDS NIH HHS/United States ; }, mesh = {Male ; Animals ; Swine ; *Ischemic Stroke ; Tumor Necrosis Factor-alpha ; *Stroke/therapy ; *Neural Stem Cells/pathology ; Inflammation/pathology ; Fatty Acids, Volatile ; *Nanoparticles ; }, abstract = {Impaired gut homeostasis is associated with stroke often presenting with leaky gut syndrome and increased gut, brain, and systemic inflammation that further exacerbates brain damage. We previously reported that intracisternal administration of Tanshinone IIA-loaded nanoparticles (Tan IIA-NPs) and transplantation of induced pluripotent stem cell-derived neural stem cells (iNSCs) led to enhanced neuroprotective and regenerative activity and improved recovery in a pig stroke model. We hypothesized that Tan IIA-NP + iNSC combination therapy-mediated stroke recovery may also have an impact on gut inflammation and integrity in the stroke pigs. Ischemic stroke was induced, and male Yucatan pigs received PBS + PBS (Control, n = 6) or Tan IIA-NP + iNSC (Treatment, n = 6) treatment. The Tan IIA-NP + iNSC treatment reduced expression of jejunal TNF-α, TNF-α receptor1, and phosphorylated IkBα while increasing the expression of jejunal occludin, claudin1, and ZO-1 at 12 weeks post-treatment (PT). Treated pigs had higher fecal short-chain fatty acid (SCFAs) levels than their counterparts throughout the study period, and fecal SCFAs levels were negatively correlated with jejunal inflammation. Interestingly, fecal SCFAs levels were also negatively correlated with brain lesion volume and midline shift at 12 weeks PT. Collectively, the anti-inflammatory and neuroregenerative treatment resulted in increased SCFAs levels, tight junction protein expression, and decreased inflammation in the gut.}, }
@article {pmid36780159, year = {2023}, author = {Sims, MD and Khanna, S and Feuerstadt, P and Louie, TJ and Kelly, CR and Huang, ES and Hohmann, EL and Wang, EEL and Oneto, C and Cohen, SH and Berenson, CS and Korman, L and Lee, C and Lashner, B and Kraft, CS and Ramesh, M and Silverman, M and Pardi, DS and De, A and Memisoglu, A and Lombardi, DA and Hasson, BR and McGovern, BH and von Moltke, L and , }, title = {Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial.}, journal = {JAMA network open}, volume = {6}, number = {2}, pages = {e2255758}, pmid = {36780159}, issn = {2574-3805}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Anti-Bacterial Agents/adverse effects ; Canada ; *Clostridioides difficile ; *Clostridium Infections/drug therapy/epidemiology ; *Microbiota ; }, abstract = {IMPORTANCE: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence.<br><br>OBJECTIVES: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks.<br><br>This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry.<br><br>INTERVENTIONS: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI.<br><br>MAIN OUTCOMES AND MEASURES: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population.<br><br>RESULTS: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]).<br><br>CONCLUSIONS AND RELEVANCE: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03183141.}, }
@article {pmid36779996, year = {2023}, author = {Scharl, M}, title = {[Which microbiota-based therapies have proven to be effective today?].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {64}, number = {4}, pages = {401-405}, pmid = {36779996}, issn = {2731-7099}, mesh = {Feces/microbiology ; Fecal Microbiota Transplantation ; *Microbiota ; *Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {BACKGROUND: There is increasing interest in the microbiota (this includes bacteria, fungi and viruses) and microbiota-based therapies. The relationship between changes in the composition of the intestinal microbiota and the pathogenesis of various diseases is of specific interest. In particular, the possibilities offered by targeted manipulation of the microbiota composition as specific treatment approaches look promising.<br><br>OBJECTIVES: This review article summarizes the current data on microbiota-based therapies as well as the evidence-based treatment options applicable for certain diseases.<br><br>RESULTS: Current data on the clinical effectiveness of microbiota-based therapies varies greatly between different diseases. While certain therapies proved successful in the treatment of some diseases, the data is still insufficient on their effectiveness in other diseases. So far, the most successful treatment in this context is fecal microbiota transplantation with a&#xa0;success rate of 80-90% for the treatment of Clostridioides difficile colitis.<br><br>CONCLUSIONS: The correction of dysbioses of the intestinal microbiota could provide new possibilities for the treatment of diseases. However, due to the lack of a&#xa0;causal-functional understanding and the mainly descriptive knowledge to date, applications are still limited. The current clinical studies addressing the changes and the importance of intestinal microbiota could lead to new therapeutic options in the treatment of diverse diseases in the future.}, }
@article {pmid36778473, year = {2023}, author = {Zhang, YJ and Bousvaros, A and Docktor, M and Kaplan, A and Rufo, PA and Leier, M and Weatherly, M and Zimmerman, L and Nguyen, LTT and Barton, B and Russell, G and Alm, EJ and Kahn, SA}, title = {Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after Fecal Microbiota Transplant in Inflammatory Bowel Disease.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36778473}, support = {K12 HD052896/HD/NICHD NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal Microbiota Transplant (FMT) has proven effective in treating recurrent Clostridioides difficile infection (rCDI) and has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. However, there is little known regarding predictors of engraftment. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC).<br><br>RESULTS: Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. The treatment arm received seven days of antibiotics followed by FMT enema and then capsules weekly for seven weeks. We enrolled four subjects with CD and 11 with UC, ages 14-29 years. Due to weekly stool sampling, we were able to create a time series of alpha diversity, beta diversity and engraftment as they related to clinical response. Subjects exhibited a wide range of microbial diversity and donor engraftment as FMT progressed. Specifically, engraftment ranged from 26% to 90% at week 2 and 3% to 92% at two months. Consistent with the current literature, increases over time of both alpha diversity (p< 0.05) and donor engraftment (p< 0.05) correlated with improved clinical response. Additionally, our weekly time series enabled an investigation into the clinical and microbial correlates of engraftment at various time points. We discovered that the post-antibiotic but pre-FMT time point, often overlooked in FMT trials, was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial with publicly available weekly sequencing data.<br><br>CONCLUSIONS: We found that higher residual alpha diversity and Lactobacillus blooms after antibiotic treatment correlated with improved engraftment and clinical response to FMT. Future studies should closely examine the host microbial communities pre-FMT and the impact of antibiotic preconditioning on engraftment and response.}, }
@article {pmid36778328, year = {2023}, author = {Borin, JM and Liu, R and Wang, Y and Wu, TC and Chopyk, J and Huang, L and Kuo, P and Ghose, C and Meyer, JR and Tu, XM and Schnabl, B and Pride, DT}, title = {Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36778328}, issn = {2692-8205}, support = {P30 DK120515/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: The gastrointestinal microbiome plays a significant role in numerous host processes and has an especially large impact on modulating the host metabolism. Prior studies have shown that when mice receive fecal transplants from obese donors that were fed high-fat diets (HFD) (even when recipient mice are fed normal diets after transplantation), they develop obese phenotypes. These studies demonstrate the prominent role that the gut microbiota play in determining lean and obese phenotypes. While much of the credit has been given to gut bacteria, studies have not measured the impact of gut viruses on these phenotypes. To address this shortcoming, we gavaged mice with viromes isolated from donors fed HFD or normal chow. By characterizing the mice’s gut bacterial biota and weight-gain phenotypes over time, we demonstrate that viruses can shape the gut bacterial community and affect weight gain or loss.<br><br>RESULTS: We gavaged mice longitudinally over 4 weeks while measuring their body weights and collecting fecal samples for 16S rRNA amplicon sequencing. We evaluated mice that were fed normal chow or high-fat diets, and gavaged each group with either chow-derived fecal viromes, HFD-derived fecal viromes, or phosphate buffered saline controls. We found a significant effect of gavage type, where mice fed chow but gavaged with HFD-derived viromes gained significantly more weight than their counterparts receiving chow-derived viromes. The converse was also true: mice fed HFD but gavaged with chow-derived viromes gained significantly less weight than their counterparts receiving HFD-derived viromes. These results were replicated in two separate experiments and the phenotypic changes were accompanied by significant and identifiable differences in the fecal bacterial biota. Notably, there were differences in Lachnospirales and Clostridia in mice fed chow but gavaged with HFD-derived fecal viromes, and in Peptostreptococcales, Oscillospirales, and Lachnospirales in mice fed HFD but gavaged with chow-derived fecal viromes. Due to methodological limitations, we were unable to identify specific bacterial species or strains that were responsible for respective phenotypic changes.<br><br>CONCLUSIONS: This study confirms that virome-mediated perturbations can alter the fecal microbiome in an in vivo model and indicates that such perturbations are sufficient to drive lean and obese phenotypes in mice.}, }
@article {pmid36777669, year = {2023}, author = {Lv, S and Zhang, Y and Zhang, Z and Meng, S and Pu, Y and Liu, X and Liu, L and Ma, Y and Liu, W and Jiang, L}, title = {Diversity of the fecal microbiota in Chinese ponies.}, journal = {Frontiers in veterinary science}, volume = {10}, number = {}, pages = {1102186}, pmid = {36777669}, issn = {2297-1769}, abstract = {INTRODUCTION: The gut microbiomes of equine are plentiful and intricate, which plays an important part in the growth. However, there is a relative lack of information on the microbial diversity in the pony's gut.<br><br>METHODS: In this article, 118 fecal samples from DeBa pony, NiQi pony and GuZh horse were studied by 16S rRNA amplicon sequencing.<br><br>RESULTS: Diversity analysis was used to determine the difference of gut microbiota composition among different breeds. Alpha diversity analysis showed that the gut microbiota of NiQi ponies were abundant and various. Beta diversity analysis showed that the microorganisms constitution of DeBa ponies was more similar to that of NiQi ponies. LDA Effect Size (LEfSe) analysis result that the microorganism biomarkers for NiQi pony at the genus level were Phascolarctobacterium, Paludibacter, and Fibrobacter; the bacterial biomarker for DeBa pony was Streptococcus and Prevotella; and the bacterial biomarkers for GuZh horses was Treponema, Treponema Mogibacterium, Adlercreutzia, and Blautia. The correlation analysis between genera with >1% abundance and horse height found that Streptococcus (P < 0.01), Treponema (P < 0.01), Coprococcus (P < 0.01), Prevotella (P < 0.01), Phascolarctobacterium (P < 0.01), and Mogibacterium (P < 0.01) were significantly associated with horses' height. The functional prediction results indicated that DeBa pony have a microbiota functional more similar to NiQi pony.<br><br>DISCUSSION: For the first time, our results announce the species composition and structure of the gut microbiota in Chinese ponies. At the same time, our results can provide theoretical reference for further understanding the healthy breeding, feeding management and disease prevention of horses.}, }
@article {pmid36777348, year = {2023}, author = {Liu, B and Zhang, L and Yang, H and Zheng, H and Liao, X}, title = {Microbiota: A potential orchestrator of antidiabetic therapy.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {973624}, pmid = {36777348}, issn = {1664-2392}, mesh = {Humans ; Hypoglycemic Agents/therapeutic use ; *Diabetes Mellitus, Type 2/drug therapy/metabolism ; *Insulin Resistance ; *Microbiota ; Inflammation ; }, abstract = {The gut microbiota, as a 'new organ' of humans, has been identified to affect many biological processes, including immunity, inflammatory response, gut-brain neural circuits, and energy metabolism. Profound dysbiosis of the gut microbiome could change the metabolic pattern, aggravate systemic inflammation and insulin resistance, and exacerbate metabolic disturbance and the progression of type 2 diabetes (T2D). The aim of this review is to focus on the potential roles and functional mechanisms of gut microbiota in the antidiabetic therapy. In general, antidiabetic drugs (α-glucosidase inhibitor, biguanides, incretin-based agents, and traditional Chinese medicine) induce the alteration of microbial diversity and composition, and the levels of bacterial component and derived metabolites, such as lipopolysaccharide (LPS), short chain fatty acids (SCFAs), bile acids and indoles. The altered microbial metabolites are involved in the regulation of gut barrier, inflammation response, insulin resistance and glucose homeostasis. Furthermore, we summarize the new strategies for antidiabetic treatment based on microbial regulation, such as pro/prebiotics administration and fecal microbiota transplantation, and discuss the need for more basic and clinical researches to evaluate the feasibility and efficacy of the new therapies for diabetes.}, }
@article {pmid36776780, year = {2023}, author = {de la Villa, S and Herrero, S and Muñoz, P and Rodríguez, C and Valerio, M and Reigadas, E and Álvarez-Uría, A and Alcalá, L and Marín, M and Olmedo, M and Kestler, M and Chamorro, E and Bouza, E}, title = {Real-world Use of Bezlotoxumab and Fecal Microbiota Transplantation for the Treatment of Clostridioides difficile Infection.}, journal = {Open forum infectious diseases}, volume = {10}, number = {2}, pages = {ofad028}, pmid = {36776780}, issn = {2328-8957}, abstract = {BACKGROUND: We aimed to describe the frequency of use and effectiveness of bezlotoxumab (BZX) and fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) in real-world practice.<br><br>METHODS: This was a retrospective study conducted in a university hospital in which adult patients treated with BZX or FMT from January 2018 to April 2021 were included. The primary objective was to evaluate the effectiveness of BZX and FMT in preventing early (within 8 weeks) and late (within 1 year) CDI recurrences (rCDI). A multivariate analysis of risk factors for early recurrence was performed.<br><br>RESULTS: Of 1377 consecutive CDI episodes, 117 (8.5%) received BZX or FMT, with full information available for 100 of the episodes: 51 received BZX, and 49 received FMT. BZX was used mostly in immunosuppressed patients (66.7%) and in first episodes or first recurrences in 70.6% of the cases. FMT was prescribed only in CDI recurrences. Despite the different conditions of the patients, there were no significant differences between BZX and FMT in preventing early rCDI (19.6% vs 24.5%; P = .55) or late rCDI (9.8% vs 18.4%; P = .31). In the multivariate analysis, risk factors for recurrence were presence of &#x2265;2 previous rCDI episodes (odds ratio [OR], 2.90; 95% CI, 1.03-8.63) and use of non-CDI antibiotics (OR, 3.45; 95% CI, 1.24-9.57).<br><br>CONCLUSIONS: BZX and FMT were infrequently used in real-world practice. Both treatments had similar effectiveness in preventing CDI recurrence despite their application to different populations.}, }
@article {pmid36774109, year = {2022}, author = {Kong, CY and Li, ZM and Chen, HL and Mao, YQ and Han, B and Guo, JJ and Wang, LS}, title = {An Energy-Restricted Diet Including Yogurt, Fruit, and Vegetables Alleviates High-Fat Diet-Induced Metabolic Syndrome in Mice by Modulating the Gut Microbiota.}, journal = {The Journal of nutrition}, volume = {152}, number = {11}, pages = {2429-2440}, doi = {10.1093/jn/nxac181}, pmid = {36774109}, issn = {1541-6100}, mesh = {Male ; Animals ; Mice ; Diet, High-Fat/adverse effects ; Vegetables ; *Metabolic Syndrome/therapy ; Obesity/metabolism ; Fruit ; *Gastrointestinal Microbiome ; Yogurt ; Mice, Inbred C57BL ; Body Weight ; *Fatty Liver ; Glucose/pharmacology ; }, abstract = {BACKGROUND: The importance of the composition of an energy-restricted diet in the treatment of metabolic syndrome (MetS) is unknown.<br><br>OBJECTIVES: In this study we aimed to investigate the benefits of a novel dietary treatment (50% calorie restriction diet composed of yogurt, fruit, and vegetables [CR-YD]) in mice with MetS.<br><br>METHODS: Forty 7-wk-old male C57BL/6 J mice were randomly assigned to 4 groups (n = 10/group) that were fed for 14 wk ad libitum with a normal diet (ND; 10%:70%:20% energy from fat: carbohydrate: protein) or for 12 wk with a high-fat diet (HFD; 60:20:20) or the HFD followed by 2 wk of feeding with a 50% calorie-restricted HFD (CR-HFD) or YD (CR-YD, 21.2%:65.4%:13.4% energy). Body weight, fat deposition, hepatic steatosis, serum concentrations of inflammatory biomarkers, and glucose homeostasis were assessed. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in MetS.<br><br>RESULTS: The HFD group had 50% greater body weight and 475% greater fat deposition than the ND group (P < 0.05). Compared with the HFD group, the CR-HFD and CR-YD groups had 22% and 31% lower body weight and 49% and 75% less fat deposition, respectively (P < 0.05). Compared with the CR-HFD group, the CR-YD group had 11% lower body weight, 96% less fat deposition, 500% less hepatic steatosis, 75% lower glucose, and 450% more hepatic Akkermansia bacteria (P < 0.05). The CR-YD group also had 50% lower histopathology scores and 1.35-fold higher levels of Claudin4 than the CR-HFD group (P < 0.05). The HFD + CR-YD fecal group had 10.6% lower body weight, 119% lower steatosis, and 17.9% lower glucose (P < 0.05) than the HFD + CR-HFD fecal group.<br><br>CONCLUSIONS: Compared with CR alone, the CR-YD diet has a better therapeutic effect in mice with HFD-induced MetS.}, }
@article {pmid36771498, year = {2023}, author = {Yun, SW and Park, HS and Shin, YJ and Ma, X and Han, MJ and Kim, DH}, title = {Lactobacillus gasseri NK109 and Its Supplement Alleviate Cognitive Impairment in Mice by Modulating NF-κB Activation, BDNF Expression, and Gut Microbiota Composition.}, journal = {Nutrients}, volume = {15}, number = {3}, pages = {}, pmid = {36771498}, issn = {2072-6643}, support = {2017R1A5A2014768//National Research Foundation of Korea/ ; 22203MFDS539//Ministry of Food and Drug Safety/ ; S3142483//Technology Development Program/ ; }, mesh = {Mice ; Animals ; NF-kappa B/metabolism ; *Lactobacillus gasseri/metabolism ; Brain-Derived Neurotrophic Factor/genetics/metabolism ; *Gastrointestinal Microbiome ; Dysbiosis ; Tumor Necrosis Factor-alpha/genetics/metabolism ; *Cognitive Dysfunction/therapy ; Mice, Transgenic ; Inflammation ; *Dementia ; Mice, Inbred C57BL ; }, abstract = {Aging-related gut microbiota dysbiosis initiates gut inflammation and microbiota dysbiosis, which induce the occurrence of psychiatric disorders including dementia. The alleviation of gut microbiota dysbiosis by probiotics is suggested to be able to alleviate psychiatric disorders including cognitive impairment (CI). Therefore, to understand how probiotics could alleviate CI, we examined the effects of anti-inflammatory Lactobacillus gasseri NK109 and its supplement (NS, mixture of NK109 and soybean embryo ethanol extract) on cognitive function in aged (Ag), 5XFAD transgenic (Tg), or mildly cognition-impaired adult fecal microbiota (MCF)-transplanted mice. Oral administration of NK109 or NS decreased CI-like behaviors in Ag mice. Their treatments suppressed TNF-α and p16 expression and NF-κB-activated cell populations in the hippocampus and colon, while BDNF expression was induced. Moreover, they partially shifted the β-diversity of gut microbiota in Ag mice to those of young mice: they decreased Bifidobacteriaceae, Lactobacillaceae, and Helicobacteriaceae populations and increased Rikenellaceae and Prevotellaceae populations. Oral administration of NK109 or NS also reduced CI-like behaviors in Tg mice. Their treatments induced BDNF expression in the hippocampus, decreased hippocampal TNF-α and Aβ expression and hippocampal and colonic NF-κB-activated cell populations. NK109 and NS partially shifted the β-diversity of gut microbiota in Tg mice: they decreased Muribaculaceae and Rhodospiraceae populations and increased Helicobacteriaceae population. Oral administration of NK109 or NS decreased MCF transplantation-induced CI-like behaviors in mice. NK109 and NS increased hippocampal BDNF expression, while hippocampal and colonic TNF-α expression and NF-κB-activated cell populations decreased. These findings suggest that dementia can fluctuate the gut microbiota composition and NK109 and its supplement NS can alleviate CI with systemic inflammation by inducing BDNF expression and suppressing NF-κB activation and gut microbiota dysbiosis.}, }
@article {pmid36771383, year = {2023}, author = {Wang, Y and Wang, X and Xiao, X and Yu, S and Huang, W and Rao, B and Chen, F}, title = {A Single Strain of Lactobacillus (CGMCC 21661) Exhibits Stable Glucose- and Lipid-Lowering Effects by Regulating Gut Microbiota.}, journal = {Nutrients}, volume = {15}, number = {3}, pages = {}, pmid = {36771383}, issn = {2072-6643}, support = {82074061//National Natural Science Foundation of China/ ; }, mesh = {*Diabetes Mellitus, Type 2/therapy ; Glucose/pharmacology ; Lactobacillus ; *Gastrointestinal Microbiome ; Dysbiosis/therapy ; Bifidobacterium ; *Probiotics ; Cholesterol, LDL ; Animals ; Lipids/pharmacology ; Mice ; }, abstract = {Type 2 diabetes (T2D) is usually accompanied by obesity and nonalcoholic fatty-liver-related insulin resistance. The link between T2D and dysbiosis has been receiving increasing attention. Probiotics can improve insulin sensitivity by regulating imbalances in microbiota, but efficacy varies based on the probiotic used. This study screened the main strain in the feces of healthy adult mice and found it to be a new Lactobacillus (abbreviated as Lb., named as CGMCC No. 21661) after genetic testing. We designed the most common Bifidobacterium longum subsp. longum (CGMCC1.2186, abbreviated as B. longum. subsp.), fecal microbiota transplantation (FMT), and Lb. CGMCC No. 21661 protocols to explore the best way for modulating dysbiosis to improve T2D. After 6 weeks of gavage in T2D mice, it was found that all three protocols had a therapeutic alleviating effect. Among them, compared with the B. longum. subsp. and FMT, the Lb. CGMCC No. 21661 showed a 1- to 2-fold decrease in blood glucose (11.84 ± 1.29 mmol/L, p < 0.05), the lowest HOMA-IR (p < 0.05), a 1 fold increase in serum glucagon-like peptide-1 (5.84 ± 1.1 pmol/L, p < 0.05), and lowest blood lipids (total cholesterol, 2.21 ± 0.68 mmol/L, p < 0.01; triglycerides, 0.4 ± 0.15 mmol/L, p < 0.01; Low-density lipoprotein cholesterol, 0.53 ± 0.16 mmol/L, p < 0.01). In addition, tissue staining in the Lb. CGMCC No. 21661 showed a 2- to 3-fold reduction in T2D-induced fatty liver (p < 0.0001), a 1- to 2-fold decrease in pancreatic apoptotic cells (p < 0.05), and a significant increase in colonic mucus layer thickness (p < 0.05) compared with the B. longum. subsp. and FMT. The glucose and lipid lowering effects of this Lb. CGMCC No. 21661 indicate that it may provide new ideas for the treatment of diabetes.}, }
@article {pmid36769429, year = {2023}, author = {Wang, W and Lu, G and Wu, X and Wen, Q and Zhang, F}, title = {Colonic Transendoscopic Enteral Tubing Is a New Pathway to Microbial Therapy, Colonic Drainage, and Host-Microbiota Interaction Research.}, journal = {Journal of clinical medicine}, volume = {12}, number = {3}, pages = {}, pmid = {36769429}, issn = {2077-0383}, support = {2021YFA0717004//National Key Research and Development Program of China/ ; }, abstract = {The limitation of traditional delivery methods for fecal microbiota transplantation (FMT) gave birth to colonic transendoscopic enteral tubing (TET) to address the requirement of frequent FMTs. Colonic TET as a novel endoscopic intervention has received increasing attention in practice since 2015 in China. Emerging studies from multiple centers indicate that colonic TET is a promising, safe, and practical delivery method for microbial therapy and administering medication with high patient satisfaction. Intriguingly, colonic TET has been used to rescue endoscopy-related perforations by draining colonic air and fluid through the TET tube. Recent research based on collecting ileocecal samples through a TET tube has contributed to demonstrating community dynamics in the intestine, and it is expected to be a novel delivery of proof-of-concept in host-microbiota interactions and pharmacological research. The present article aims to review the concept and techniques of TET and to explore microbial therapy, colonic drainage, and microbial research based on colonic TET.}, }
@article {pmid36768173, year = {2023}, author = {Panebianco, C and Villani, A and Potenza, A and Favaro, E and Finocchiaro, C and Perri, F and Pazienza, V}, title = {Targeting Gut Microbiota in Cancer Cachexia: Towards New Treatment Options.}, journal = {International journal of molecular sciences}, volume = {24}, number = {3}, pages = {}, pmid = {36768173}, issn = {1422-0067}, support = {IG 2019 - ID. 23006 project//Italian Association for Cancer Research/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Cachexia/therapy/complications ; Quality of Life ; *Probiotics/therapeutic use ; Prebiotics ; *Neoplasms/complications/therapy ; Fecal Microbiota Transplantation ; Dysbiosis/complications/therapy ; }, abstract = {Cancer cachexia is a complex multifactorial syndrome whose hallmarks are weight loss due to the wasting of muscle tissue with or without the loss of adipose tissue, anorexia, systemic inflammation, and multi-organ metabolic alterations, which negatively impact patients' response to anticancer treatments, quality of life, and overall survival. Despite its clinical relevance, cancer cachexia often remains an underestimated complication due to the lack of rigorous diagnostic and therapeutic pathways. A number of studies have shown alterations in gut microbiota diversity and composition in association with cancer cachexia markers and symptoms, thus supporting a central role for dysbiosis in the pathogenesis of this syndrome. Different tools of microbiota manipulation, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been investigated, demonstrating encouraging improvements in cachexia outcomes. Albeit pioneering, these studies pave the way for future research with the aim of exploring the role of gut microbiota in cancer cachexia more deeply and setting up effective microbiota-targeting interventions to be translated into clinical practice.}, }
@article {pmid36768140, year = {2023}, author = {Majait, S and Nieuwdorp, M and Kemper, M and Soeters, M}, title = {The Black Box Orchestra of Gut Bacteria and Bile Acids: Who Is the Conductor?.}, journal = {International journal of molecular sciences}, volume = {24}, number = {3}, pages = {}, pmid = {36768140}, issn = {1422-0067}, mesh = {Humans ; Bile Acids and Salts/metabolism ; *Diabetes Mellitus, Type 2 ; Bacteria/metabolism ; *Microbiota ; *Gastrointestinal Microbiome/physiology ; }, abstract = {Over the past decades the potential role of the gut microbiome and bile acids in type 2 diabetes mellitus (T2DM) has been revealed, with a special reference to low bacterial alpha diversity. Certain bile acid effects on gut bacteria concern cytotoxicity, or in the case of the microbiome, bacteriotoxicity. Reciprocally, the gut microbiome plays a key role in regulating the bile acid pool by influencing the conversion and (de)conjugation of primary bile acids into secondary bile acids. Three main groups of bacterial enzymes responsible for the conversion of bile acids are bile salt hydrolases (BSHs), hydroxysteroid dehydrogenases (HSDHs) and enzymes encoded in the bile acid inducible (Bai) operon genes. Interventions such as probiotics, antibiotics and fecal microbiome transplantation can impact bile acids levels. Further evidence of the reciprocal interaction between gut microbiota and bile acids comes from a multitude of nutritional interventions including macronutrients, fibers, prebiotics, specific individual products or diets. Finally, anatomical changes after bariatric surgery are important because of their metabolic effects. The heterogeneity of studies, diseases, bacterial species and (epi)genetic influences such as nutrition may challenge establishing specific and detailed interventions that aim to tackle the gut microbiome and bile acids.}, }
@article {pmid36765735, year = {2023}, author = {Knisely, A and Seo, YD and Wargo, JA and Chelvanambi, M}, title = {Monitoring and Modulating Diet and Gut Microbes to Enhance Response and Reduce Toxicity to Cancer Treatment.}, journal = {Cancers}, volume = {15}, number = {3}, pages = {}, pmid = {36765735}, issn = {2072-6694}, support = {T32 CA009599/CA/NCI NIH HHS/United States ; T32 CA101642/CA/NCI NIH HHS/United States ; }, abstract = {The gut microbiome comprises a diverse array of microbial species that have been shown to dynamically modulate host immunity both locally and systemically, as well as contribute to tumorigenesis. In this review, we discuss the scientific evidence on the role that gut microbes and diet play in response and toxicity to cancer treatment. We highlight studies across multiple cancer cohorts that have shown an association between particular gut microbiome signatures and an improved response to immune checkpoint blockade, chemotherapy, and adoptive cell therapies, as well as the role of particular microbes in driving treatment-related toxicity and how the microbiome can be modulated through strategies, such as fecal transplant. We also summarize the current literature that implicate high fiber and ketogenic diets in improved response rates to immunotherapy and chemotherapy, respectively. Finally, we discuss the relevance of these findings in the context of patient care, advocate for a holistic approach to cancer treatment, and comment on the next frontier of targeted gut and tumor microbiome modulation through novel therapeutics, dietary intervention, and precision-medicine approaches.}, }
@article {pmid36761896, year = {2023}, author = {Qian, W and Wu, M and Qian, T and Xie, C and Gao, Y and Qian, S}, title = {The roles and mechanisms of gut microbiome and metabolome in patients with cerebral infarction.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1112148}, pmid = {36761896}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Feces ; Cerebral Infarction ; *Stroke ; Metabolome ; Fecal Microbiota Transplantation ; }, abstract = {As the most common type of stroke, ischemic stroke, also known as cerebral infarction (CI), with its high mortality and disability rate, has placed a huge burden on social economy and public health. Treatment methods for CI mainly include thrombectomy, thrombolysis, drug therapy, and so on. However, these treatments have certain timeliness and different side effects. In recent years, the gut-brain axis has become a hot topic, and its role in nervous system diseases has been confirmed by increasing evidences. The intestinal microbiota, as an important part of the gut-brain axis, has a non-negligible impact on the progression of CI through mechanisms such as inflammatory response and damage-associated molecular patterns, and changes in the composition of intestinal microbiota can also serve as the basis for predicting CI. At the same time, the diagnosis of CI requires more high-throughput techniques, and the analysis method of metabolomics just fits this demand. This paper reviewed the changes of intestinal microbiota in patients within CI and the effects of the intestinal microbiota on the course of CI, and summarized the therapeutic methods of the intervention with the intestinal microbiota. Furthermore, metabolic changes of CI patients were also discussed to reveal the molecular characteristics of CI and to elucidate the potential pathologic pathway of its interference.}, }
@article {pmid36758789, year = {2023}, author = {Ouyang, S and Wang, X and Chen, Y and Deng, L and Yang, X and Hu, S and Wu, S}, title = {Swimming training combined with fecal microbial transplantation protects motor functions in rats with spinal cord injury by improving the intestinal system.}, journal = {Neuroscience letters}, volume = {799}, number = {}, pages = {137104}, doi = {10.1016/j.neulet.2023.137104}, pmid = {36758789}, issn = {1872-7972}, mesh = {Rats ; Animals ; Rats, Sprague-Dawley ; *Swimming ; *Spinal Cord Injuries/pathology ; Spinal Cord/metabolism ; Gastrointestinal Tract/metabolism ; Recovery of Function/physiology ; }, abstract = {Spinal cord injury (SCI) leads to severe intestinal dysfunction and decreased motility. There is an interaction between the intestine and the nervous system, intestinal intervention through microbial regulation and exercise is a potential treatment option for spinal cord injury. We investigated the effects of swimming rehabilitation training combined with fecal microbial transplantation on intestinal as well as neurological functions in rats with spinal cord injuries, and explored the potential mechanisms. The animals were randomly divided into five groups: sham-operated control group (Sham), spinal cord injury only group (SCI), swimming training group (Swimming), fecal microbial transplantation group (FMT) and combined interventions group (Combined). Behavioral assessments, pathological and immunological analyses were performed after the interventions. Compared to rats in the spinal cord injury group, rats subjected to swimming training, fecal microbial transplantation and combined interventions group exhibited improved intestinal transit, barrier functions, motility, and motor conduction pathway conductivity(P < 0.05). The combined interventions group had better outcomes(P < 0.01). In addition, combined interventions significantly suppressed inflammatory factor levels (P < 0.05) in the colon and spinal cords and significantly protected forefoot motor neurons (NeuN) in the spinal cord injury area, inhibiting astrocyte activation and reducing the expressions of the signature glial fibrillary acidic protein (GFAP) and markers of microglia (Iba-1) at the lesion site(P < 0.05). In conclusion, all effects of combined swimming training and fecal microbial transplantation interventions were superior to swimming training or fecal microbial transplantation alone. Swimming training and fecal microbial transplantation interventions have a synergistic effect on the recovery of intestinal function and motility after spinal cord injury. The mechanism of mutual facilitation between gut function and motility may be related to the brain-gut axis interaction.}, }
@article {pmid36757537, year = {2023}, author = {Shao, T and Hsu, R and Hacein-Bey, C and Zhang, W and Gao, L and Kurth, MJ and Zhao, H and Shuai, Z and Leung, PSC}, title = {The Evolving Landscape of Fecal Microbial Transplantation.}, journal = {Clinical reviews in allergy &amp; immunology}, volume = {65}, number = {2}, pages = {101-120}, pmid = {36757537}, issn = {1559-0267}, mesh = {Humans ; Fecal Microbiota Transplantation ; Feces ; *Clostridioides difficile/physiology ; *Microbiota ; *Clostridium Infections/therapy ; *Neoplasms ; Treatment Outcome ; }, abstract = {The human gastrointestinal tract houses an enormous microbial ecosystem. Recent studies have shown that the gut microbiota plays significant physiological roles and maintains immune homeostasis in the human body. Dysbiosis, an imbalanced gut microbiome, can be associated with various disease states, as observed in infectious diseases, inflammatory diseases, autoimmune diseases, and cancer. Modulation of the gut microbiome has become a therapeutic target in treating these disorders. Fecal microbiota transplantation (FMT) from a healthy donor restores the normal gut microbiota homeostasis in the diseased host. Ample evidence has demonstrated the efficacy of FMT in recurrent Clostridioides difficile infection (rCDI). The application of FMT in other human diseases is gaining attention. This review aims to increase our understanding of the mechanisms of FMT and its efficacies in human diseases. We discuss the application, route of administration, limitations, safety, efficacies, and suggested mechanisms of FMT in rCDI, autoimmune diseases, and cancer. Finally, we address the future perspectives of FMT in human medicine.}, }
@article {pmid36757169, year = {2023}, author = {Stulic, M and Culafic, D and Jordovic, J and Culafic, M and Petrovic, N and Stojimirov, I and Loncar, Z}, title = {West Nile Virus Infection in Liver Transplant Recipient With Neither De Novo Infection nor Donor-Derived Infection: A Case Report.}, journal = {Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation}, volume = {21}, number = {1}, pages = {59-62}, doi = {10.6002/ect.2022.0226}, pmid = {36757169}, issn = {2146-8427}, mesh = {Male ; Animals ; Horses ; *West Nile Fever/diagnosis/drug therapy ; *Kidney Transplantation ; *Liver Transplantation/adverse effects ; Mycophenolic Acid/therapeutic use ; *West Nile virus ; }, abstract = {West Nile virus was first described in 1937 and has sinceperiodically appearedin variousparts oftheworld by infecting people and horses. Reported infection symptoms and signs may be highly variable, ranging from fever and myalgias to meningoencephalitis. A 59-year-old patient was admitted to the University Clinical Centre of Serbia, Belgrade, in September 2018, where livertransplantwasperformedtotreat cirrhosisof ethyl etiology. Immunosuppressive therapy was started immediately after successful transplant, with the patientreceiving methylprednisolone, tacrolimus, and mycophenolate mofetil. Mycophenolate mofetil was excluded from therapy on postoperative day 3 because of progressively worse white blood cell count. The patient became febrile on postoperative day 11 (39.6 °C), and arm tremor, nausea, vomiting, and frequent fluid stools occurred. He complained of pain in the muscles and joints of the lower extremities. The next day he experienced occasional disorientation. Neurological findings revealed no signs of acute focal neurological deficit. We performed culture tests to isolate pathological microorganisms, and results were negative in cultures of the blood, urine, feces, ascites, and a smear of the wound and tip of the central venous catheter. Lumbar puncture resulted in a clear cerebrospinal fluid that was sent for analysis that showed significant increases in white blood cell count (94 × 106 cells/L), total proteins (1.61 g/L), and microalbumin (504.5 mg/L), with a reduction of immunoglobulin G. On postoperative day 15, positive serology of West Nile virus immunoglobulin M in cerebrospinal fluid was verified. Intensive monitoring and symptomatic and supportive therapy resulted in clinical and laboratory improvement, and the patient was discharged in good general condition on postoperative day 22. Considering the high risk of posttransplant complications, there remains the question of whether all donors and recipients should be tested forWest Nile virus atthe onset oftransplant.}, }
@article {pmid36756869, year = {2023}, author = {Chopra, T}, title = {A profile of the live biotherapeutic product RBX2660 and its role in preventing recurrent Clostridioides difficile infection.}, journal = {Expert review of anti-infective therapy}, volume = {21}, number = {3}, pages = {243-253}, doi = {10.1080/14787210.2023.2171986}, pmid = {36756869}, issn = {1744-8336}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile ; *Clostridium Infections/drug therapy ; *Gastrointestinal Microbiome ; *Microbiota ; Recurrence ; }, abstract = {INTRODUCTION: Clostridiodes difficile infection (CDI) is a life-threatening illness that has been labelled as an urgent threat by the Centers for Disease prevention (CDC).<br><br>AREAS COVERED: RBX2660, a live biotherapeutic product offers a very promising treatment option for patients with recurrent Clostridiodes difficile infection(rCDI). RBX2660 restores the healthy gut microbiome and shows clinically meaningful benefits for patients suffering from rCDI. Safety, efficacy, and tolerability of RBX2660 have been thoroughly assessed .<br><br>EXPERT OPINION: An FDA-approved, standardized, and accessible microbiota restoration product like RBX2660 would provide a new option for patients in need of treatment for rCDI by breaking the cycle of disease recurrence.}, }
@article {pmid36756616, year = {2023}, author = {Varga, A and Makszin, L and Bufa, A and Sipos, D and Kása, P and Pál, S and Rosenstiel, P and Sommer, F and Kocsis, B and Péterfi, Z}, title = {Efficacy of lyophilised bacteria-rich faecal sediment and supernatant with reduced bacterial count for treating patients with Clostridioides difficile Infection - A novel method for capsule faecal microbiota transfer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1041384}, pmid = {36756616}, issn = {2235-2988}, mesh = {Humans ; Fecal Microbiota Transplantation ; Bacterial Load ; Capsules ; *Clostridioides difficile ; Feces/microbiology ; *Clostridium Infections/therapy/microbiology ; Bacteria ; Lipids ; Treatment Outcome ; Recurrence ; }, abstract = {BACKGROUND AND AIMS: Faecal microbiota transfer (FMT) has managed to earn its place in the Clostridioides difficile infection (CDI) guidelines by having comparable efficacy and recurrence rate of fidaxomicin. After more than 100 successful FMT administration through nasogastric tube, we started using hard gelatine capsules filled with lyophilised faecal sediment and supernatant. Our main question was whether uncoated capsules (containing faecal sediment or supernatant) are comparable to the widely used nasogastric tubes in CDI. We also investigated the effect of storage and time on the survival rate of bacteria in the samples.<br><br>METHODS: We compared the efficacy of our capsules to other treatment options of CDI at the Department of Infectology at the University of P&#xe9;cs (Hungary). For our study, stool was collected from a single donor. We treated 10 patients with relapsing CDI, 5 of them received supernatant, 5 received sediment. Donor samples were stored on 4 different temperatures and tested to determine the survival rates of bacteria. As pilot projects, we also assessed the changes of bacterial taxa, protein- and lipid compositions. Moreover, we selected 4 patients to compare their samples prior and after FMT by using microbiome (16S amplicon sequencing), protein, and lipid analyses.<br><br>RESULTS: 4 out of the 5 patients who received supernatant became symptomless within 2 days after FMT. In the sediment group 3 out of 5 patients were cured from CDI. Comparing the supernatant to the sediment, we found significantly lower number of colony-forming units in the supernatant. We found that -80&#xb0;C is the most suitable temperature to store the samples. The stool lipid profiles of recipients showed a more diverse composition after FMT, and changes in the stool protein profiles were observed as well. In the microbiome analysis, we observed an increase in the alpha diversity after FMT.<br><br>CONCLUSIONS: Our study of 10 patients showed good efficacy of lyophilised faecal supernatant using capsules. The single donor approach proved to be effective in our investigation. A significantly lower CFU number was sufficient for the effect, the separation can be achieved by widely available instruments. For storage temperature, -20&#xb0;C was sufficient in our clinical practice.}, }
@article {pmid36755640, year = {2022}, author = {Kalra, SJS and Shankar, H and Mansoori, N and Gupta, DL}, title = {Antibiotic-resistant bacteria originating from the gut may modulate the mucosal immune response during sepsis and septic shock.}, journal = {Drug target insights}, volume = {16}, number = {}, pages = {81-87}, pmid = {36755640}, issn = {1177-3928}, abstract = {The enrichment and diversity of gut microbiota play an important role in sepsis, but the role of gut microbiota composition and early-life colonization in sepsis and septic shock has not yet been characterized. The impact of gut microbiota diversity on host immunological disorders and future treatments of inflammatory diseases are not yet fully elucidated. Further, the association between the microbiota and immune development in sepsis remains unknown, and the underlying mechanisms are not well understood. The altered composition of gut microbiota during sepsis is profoundly associated with a loss of commensal bacteria and an overgrowth of potentially pathogenic bacteria, especially AMR bacteria. Disruptions of gut microbiota diversity are directly associated with susceptibility to sepsis and a higher risk of adverse outcomes. Several studies have confirmed that a mutual association between gut microbiota and the host is important for the metabolism of essential nutrients for the organism, for gut development, and for the maturation and development of a fully functional immune system. Therefore, understanding the gut microbiota diversity, composition, and function during various inflammatory conditions and sepsis may provide a comprehensive knowledge of the mechanisms behind the pathogenesis of gut-derived infection in diseases and the design of new treatment options (e.g., probiotics or fecal microbiota transplantation). Emerging evidence displays an important role of gut microbiota and their derived metabolites in modulating the host mucosal immune response and determining the susceptibility to, as well as outcomes of sepsis.}, }
@article {pmid36753681, year = {2023}, author = {Wang, Z and Yao, W and Sun, Y and Han, Y and Chen, X and Gong, P and Zhai, P and Pei, S and Xie, J and Ba, Q and Wang, H}, title = {Eucommia Bark/Leaf Extract Improves Lipid Metabolism Disorders by Affecting Intestinal Microbiota and Microbiome-Host Interaction in HFD Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c07239}, pmid = {36753681}, issn = {1520-5118}, abstract = {Eucommia bark contains many bioactive compounds and has anti-hyperlipidemic effects. However, due to the slow growth rate of the plant, there is a limited supply of this resource. Studies have demonstrated that Eucommia leaves contain active ingredients similar to those of Eucommia bark and also have anti-hyperlipidemic effects. It is not currently clear whether Eucommia leaf can be used as a substitute for Eucommia bark. Furthermore, their mechanism of action for anti-hyperlipidemia by improving the structure of the gut microbiota is also unclear. We aimed to determine the composition of the active ingredients in EBE and ELE by HPLC, establish an HFD-induced hyperlipidemia model, and combine fecal microbiota transplantation (FMT) experiments to investigate the mechanism of EBE/ELE anti-hyperlipidemia by modifying the structure of intestinal microbiota, as well as to compare the effects of EBE and ELE. Our results showed that EBE and ELE contained similar active ingredients and significantly alleviated lipid metabolism disorders and blood glucose levels in the HFD-induced hyperlipidemia model. In this study, EBE and ELE significantly reduced the relative abundance of Desulfovibrionaceae and Erysipelotrichaceae and significantly increased the relative abundance of Ruminococcaceae. They also promoted the production of short-chain fatty acids (SCFAs) and activated the gene expression of the SCFA receptors G protein-coupled receptor 41 (GPR41) and GPR43. In addition, EBE and ELE can significantly increase the expression of the fasting-induced adipose factor (Fiaf) gene in the colon and inhibit the secretion of lipoprotein lipase (LPL) in the liver, thereby inhibiting triglyceride (TG) synthesis. They also significantly activate the expression of GPR41 and GPR43 genes in the epididymal fat tissue, leading to reduced lipid accumulation in adipocytes. These effects on the target genes were associated with changes in the abundance of Desulfovibrionaceae, Erysipelotrichaceae, and Ruminococcaceae bacteria in the intestinal microbiota. Thus, regulating the relative abundance of these microbes may serve as prospective targets for EBE/ELE to influence the Fiaf-LPL gut-liver axis and the SCFAs-GPR41/GPR43 gut-fat axis. In addition, there was no significant difference in the anti-hyperlipidemic effects of ELE and EBE, suggesting that Eucommia leaf may be a suitable alternative to Eucommia bark for managing hyperlipidemia by regulating the structure of the intestinal microbiota. These findings suggest that Eucommia leaves have great potential for development as a functional food with lipid-lowering properties.}, }
@article {pmid36752887, year = {2023}, author = {Garcia, N and Gutierrez, E}, title = {Anorexia nervosa and microbiota: systematic review and critical appraisal.}, journal = {Eating and weight disorders : EWD}, volume = {28}, number = {1}, pages = {1}, pmid = {36752887}, issn = {1590-1262}, mesh = {Animals ; Humans ; *Anorexia Nervosa/complications ; *Microbiota ; *Gastrointestinal Microbiome ; Feces ; }, abstract = {PURPOSE: Recent studies have reported a gut microbiota imbalance or dysbiosis associated with anorexia nervosa (AN), which has prompted an appraisal of its aetiological role, and the reformulation of AN as a metabo-psychiatric disorder. Thus, the aim of this paper was to critically review the current scientific findings regarding the role of microbiota in anorexia nervosa.<br><br>METHODS: A systematic study of peer-reviewed literature published in four databases between 2009 and 2022 was conducted according to PRISMA guidelines. Both human and animal studies were included.<br><br>RESULTS: A total of 18 studies were included. In animal models, both the preclinical and clinical findings were inconsistent regarding microbiota composition, faecal metabolite concentrations, and the effects of human faecal microbiota transplants.<br><br>CONCLUSION: The methodological limitations, lack of standardisation, and conceptual ambiguity hinder the analysis of microbiota as a key explanatory factor for AN.<br><br>LEVEL OF EVIDENCE: Level I, systematic review.}, }
@article {pmid36752740, year = {2023}, author = {Liu, D and Tian, Q and Liu, K and Ren, F and Liu, G and Zhou, J and Yuan, L and Fang, Z and Zou, B and Wang, S}, title = {Ginsenoside Rg3 Ameliorates DSS-Induced Colitis by Inhibiting NLRP3 Inflammasome Activation and Regulating Microbial Homeostasis.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.2c07766}, pmid = {36752740}, issn = {1520-5118}, abstract = {Ulcerative colitis (UC) is a recurrent inflammatory disease without a specific cure or treatment for improvement. Here, we investigated the potential therapeutic effect and mechanism of ginsenoside Rg3 (Gin Rg3) on UC. We constructed an in vitro cellular inflammatory model and a dextran sulfate sodium (DSS)-induced UC mouse model. We also used Gin Rg3, MCC950 (NLRP3 inhibitor), MSU (NLRP3 activator), and fecal transplantation (FMT) to intervene the model. The results showed that Gin Rg3 inhibited NLRP3 inflammasome activation, pyroptosis, and apoptosis in vitro and in vivo. DSS-induced changes in the abundance of gut microbiota at the phylum or genus level were partially restored by Gin Rg3. Furthermore, gin Rg3 affected intestinal metabolism in mice by inhibiting the activation of NLRP3 inflammasome. The gut microbiota treated with Gin Rg3 was sufficient to alleviate DSS-induced UC. In summary, Gin Rg3 alleviated DSS-induced UC by inhibiting NLRP3 inflammasome activation and regulating gut microbiota homeostasis.}, }
@article {pmid36751730, year = {2023}, author = {Nørgaard, JC and Jørgensen, M and Moestrup, KS and Ilett, EE and Zucco, AG and Marandi, RZ and Julian, MN and Paredes, R and Lundgren, JD and Sengeløv, H and MacPherson, C}, title = {Impact of Antibiotic Treatment on the Gut Microbiome and its Resistome in Hematopoietic Stem Cell Transplant Recipients.}, journal = {The Journal of infectious diseases}, volume = {228}, number = {1}, pages = {28-36}, doi = {10.1093/infdis/jiad033}, pmid = {36751730}, issn = {1537-6613}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Anti-Bacterial Agents/adverse effects ; Drug Resistance, Microbial/genetics ; Bacteria/genetics ; *Hematopoietic Stem Cell Transplantation/adverse effects ; }, abstract = {Antibiotic-resistant bacterial infections are increasingly an issue in allogenic hematopoietic stem cell transplant patients. How antibiotic treatment impacts antibiotic resistance in the human gut microbiome remains poorly understood in vivo. Here, a total of 577 fecal samples from 233 heavily antibiotic-treated transplant patients were examined using high-resolution prescription data and shotgun metagenomics. The 13 most frequently used antibiotics were significantly associated with 154 (40% of tested associations) microbiome features. Use of broad-spectrum β-lactam antibiotics was most markedly associated with microbial disruption and increase in resistome features. The enterococcal vanA gene was positively associated with 8 of the 13 antibiotics, and in particular piperacillin/tazobactam and vancomycin. Here, we highlight the need for a high-resolution approach in understanding the development of antibiotic resistance in the gut microbiome. Our findings can be used to inform antibiotic stewardship and combat the increasing threat of antibiotic resistance.}, }
@article {pmid36749386, year = {2023}, author = {Tanaka, Y and Yamashita, R and Kawashima, J and Mori, H and Kurokawa, K and Fukuda, S and Gotoh, Y and Nakamura, K and Hayashi, T and Kasahara, Y and Sato, Y and Fukudo, S}, title = {Further notice of omics profiles of fecal and oral microbiota change in irritable bowel syndrome patients with diarrhea and symptom exacerbation.}, journal = {Journal of gastroenterology}, volume = {58}, number = {4}, pages = {427-428}, pmid = {36749386}, issn = {1435-5922}, support = {17K17584//JSPS KAKENHI/ ; 16H06279 (PAGS)//JSPS KAKENHI/ ; 19K22589//JSPS KAKENHI/ ; SRF//JSPS KAKENHI/ ; JST ERATO JPMJER1902//JSPS KAKENHI/ ; JP21gm1010009//AMED-CREST/ ; }, mesh = {Humans ; *Irritable Bowel Syndrome/diagnosis ; Symptom Flare Up ; Diarrhea/etiology/diagnosis ; Feces ; *Microbiota ; Fecal Microbiota Transplantation ; }, }
@article {pmid36746362, year = {2023}, author = {Ma, J and Liu, Z and Gao, X and Bao, Y and Hong, Y and He, X and Zhu, W and Li, Y and Huang, W and Zheng, N and Sheng, L and Zhou, B and Chen, H and Li, H}, title = {Gut microbiota remodeling improves natural aging-related disorders through Akkermansia muciniphila and its derived acetic acid.}, journal = {Pharmacological research}, volume = {189}, number = {}, pages = {106687}, doi = {10.1016/j.phrs.2023.106687}, pmid = {36746362}, issn = {1096-1186}, mesh = {Verrucomicrobia/genetics ; Akkermansia ; Acetic Acid ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/genetics ; Mice ; Animals ; }, abstract = {Accumulating evidence indicates gut microbiota contributes to aging-related disorders. However, the exact mechanism underlying gut dysbiosis-related pathophysiological changes during aging remains largely unclear. In the current study, we first performed gut microbiota remodeling on old mice by fecal microbiota transplantation (FMT) from young mice, and then characterized the bacteria signature that was specifically altered by FMT. Our results revealed that FMT significantly improved natural aging-related systemic disorders, particularly exerted hepatoprotective effects, and improved glucose sensitivity, hepatosplenomegaly, inflammaging, antioxidative capacity and intestinal barrier. Moreover, FMT particularly increased the abundance of fecal A.muciniphila, which was almost nondetectable in old mice. Interestingly, A.muciniphila supplementation also exerted similar benefits with FMT on old mice. Notably, targeted metabolomics on short chain fatty acids (SCFAs) revealed that only acetic acid was consistently reversed by FMT. Then, acetic acid intervention exerted beneficial actions on both Caenorhabditis elegans and natural aging mice. In conclusion, our current study demonstrated that gut microbiota remodeling improved natural aging-related disorders through A.muciniphila and its derived acetic acid, suggesting that interventions with potent stimulative capacity on A. muciniphila growth and production of acetic acid was alternative and effective way to maintain healthy aging. DATA AVAILABILITY STATEMENT: The data of RNAseq and 16 S rRNA gene sequencing can be accessed in NCBI with the accession number PRJNA848996 and PRJNA849355.}, }
@article {pmid36742327, year = {2023}, author = {Morse, ZJ and Simister, RL and Crowe, SA and Horwitz, MS and Osborne, LC}, title = {Virus induced dysbiosis promotes type 1 diabetes onset.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1096323}, pmid = {36742327}, issn = {1664-3224}, mesh = {Humans ; Animals ; Mice ; *Diabetes Mellitus, Type 1 ; Mice, Inbred NOD ; Dysbiosis/complications ; Intestines/microbiology ; *Enterovirus Infections/complications ; Genetic Predisposition to Disease ; }, abstract = {Autoimmune disorders are complex diseases of unclear etiology, although evidence suggests that the convergence of genetic susceptibility and environmental factors are critical. In type 1 diabetes (T1D), enterovirus infection and disruption of the intestinal microbiota are two environmental factors that have been independently associated with T1D onset in both humans and animal models. However, the possible interaction between viral infection and the intestinal microbiota remains unknown. Here, we demonstrate that Coxsackievirus B4 (CVB4), an enterovirus that accelerates T1D onset in non-obese diabetic (NOD) mice, induced restructuring of the intestinal microbiome prior to T1D onset. Microbiome restructuring was associated with an eroded mucosal barrier, bacterial translocation to the pancreatic lymph node, and increased circulating and intestinal commensal-reactive antibodies. The CVB4-induced change in community composition was strikingly similar to that of uninfected NOD mice that spontaneously developed diabetes, implying a mutual "diabetogenic" microbiome. Notably, members of the Bifidobacteria and Akkermansia genera emerged as conspicuous members of this diabetogenic microbiome, implicating these taxa, among others, in diabetes onset. Further, fecal microbiome transfer (FMT) of the diabetogenic microbiota from CVB4-infected mice enhanced T1D susceptibility and led to diminished expression of the short chain fatty acid receptor GPR43 and fewer IL-10-expressing regulatory CD4[+] T cells in the intestine of naïve NOD recipients. These findings support an overlap in known environmental risk factors of T1D, and suggest that microbiome disruption and impaired intestinal homeostasis contribute to CVB-enhanced autoreactivity and T1D.}, }
@article {pmid36737985, year = {2023}, author = {Wang, L and Zhang, P and Chen, J and Li, C and Tian, Y and Xu, F}, title = {Prebiotic properties of the polysaccharide from Rosa roxburghii Tratt fruit and its protective effects in high-fat diet-induced intestinal barrier dysfunction: A fecal microbiota transplantation study.}, journal = {Food research international (Ottawa, Ont.)}, volume = {164}, number = {}, pages = {112400}, doi = {10.1016/j.foodres.2022.112400}, pmid = {36737985}, issn = {1873-7145}, mesh = {Animals ; Mice ; Fecal Microbiota Transplantation ; *Rosa ; Prebiotics ; Diet, High-Fat/adverse effects ; Fruit ; *Colitis/chemically induced ; Polysaccharides/pharmacology ; }, abstract = {Polysaccharide from Rosa roxburghii Tratt fruit (RTFP) ameliorates high-fat diet (HFD)-induced colitis in mice. However, it is still unknown whether the gut microbiota can mediate the anti-colitis effects of RTFP in mice. This research aims to investigate the role of gut microbes in modulating RTFP in colitis mice through fecal microbiota transplantation (FMT). The findings demonstrated that RTFP exhibited prebiotic effects on HFD-induced colitis mice. After FMT treatment (transplatation of the microbiota from the fecal sample to each recipient daily), the fecal microbiota of RTFP-treated donor mice remarkably alleviated colitis-related symptoms (e.g., colonic inflammation, loss of body weight, gut microbiota dysbiosis, and loss of barrier integrity) and upregulated the expression of tight junction proteins compared to the HFD-treated donor mice. Overall, RTFP can reduce the severity of HFD-induced colitis by regulating gut microbiota.}, }
@article {pmid36737487, year = {2023}, author = {Poto, R and Laniro, G and de Paulis, A and Spadaro, G and Marone, G and Gasbarrini, A and Varricchi, G}, title = {Is there a role for microbiome-based approach in common variable immunodeficiency?.}, journal = {Clinical and experimental medicine}, volume = {23}, number = {6}, pages = {1981-1998}, pmid = {36737487}, issn = {1591-9528}, mesh = {Humans ; *Common Variable Immunodeficiency/therapy/etiology ; *Microbiota ; *Gastrointestinal Microbiome ; *Autoimmune Diseases ; }, abstract = {Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. CVID embraces a plethora of heterogeneous manifestations linked to complex immune dysregulation. While CVID is thought to be due to genetic defects, the exact cause of this immune disorder is unknown in the large majority of cases. Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. Here we discuss the potential of treating CVID patients by developing a gut microbiome-based personalized approach, including diet, prebiotics, probiotics, postbiotics and fecal microbiota transplantation. We also highlight the need for a better understanding of microbiota-host interactions in CVID patients to prime the development of improved preventive strategies and specific therapeutic targets.}, }
@article {pmid36736919, year = {2023}, author = {L, K and Ng, TKS and Wee, HN and Ching, J}, title = {Gut-brain axis through the lens of gut microbiota and their relationships with Alzheimer's disease pathology: Review and recommendations.}, journal = {Mechanisms of ageing and development}, volume = {211}, number = {}, pages = {111787}, doi = {10.1016/j.mad.2023.111787}, pmid = {36736919}, issn = {1872-6216}, mesh = {Animals ; Humans ; *Alzheimer Disease/pathology ; *Gastrointestinal Microbiome/physiology ; Brain-Gut Axis ; *Diabetes Mellitus, Type 2 ; Brain/pathology ; }, abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. Growing evidence suggests that the gut microbiome (GM) plays a pivotal role in the pathogenesis of AD through the microbiota-gut-brain axis (MGB). Alterations in GM composition and diversity have been observed in both animal models and in human patients with AD. GM dysbiosis has been implicated in increased intestinal permeability, blood-brain barrier (BBB) impairment, neuroinflammation and the development of hallmarks of AD. Further elucidation of the role of GM in AD could pave way for the development of holistic predictive methods for determining AD risk and progression of disease. Furthermore, accumulating evidence suggests that GM modulation could alleviate adverse symptoms of AD or serve as a preventive measure. In addition, increasing evidence shows that Type 2 Diabetes Mellitus (T2DM) is often comorbid with AD, with common GM alterations and inflammatory response, which could chart the development of GM-related treatment interventions for both diseases. We conclude by exploring the therapeutic potential of GM in alleviating symptoms of AD and in reducing risk. Furthermore, we also propose future directions in AD research, namely fecal microbiota transplantation (FMT) and precision medicine.}, }
@article {pmid36735734, year = {2023}, author = {Lee, C and Kim, S and Kim, B and Holzapfel, WH and Hyun, CK}, title = {Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice.}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0280850}, pmid = {36735734}, issn = {1932-6203}, mesh = {Animals ; Mice ; Adiponectin/metabolism ; Cholesterol ; *Colitis/chemically induced/metabolism ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Dysbiosis ; *Gastrointestinal Microbiome/physiology ; *Inflammatory Bowel Diseases ; *Insulins ; Lipid Metabolism ; Mice, Inbred C57BL ; }, abstract = {Hepatobiliary abnormality and metabolic disorders are frequently observed complications in patients with inflammatory bowel diseases (IBD). Given that microbiota dysbiosis is a common pathophysiological feature of both IBD and metabolic diseases, we examined how the IBD-induced dysbiosis affects the host metabolism and contributes to the development of associated metabolic diseases using germ-free (GF) mice transplanted with fecal microbiota of DSS-induced colitis mice. There was no significant change in inflammation or barrier integrity in the gut of GF mice that received microbiota from colitis mice compared to their counterparts that were transplanted with microbiota from non-colitis healthy mice. Interestingly, it was observed that the GF recipients of colitis-induced altered microbiota showed a significant decrease in the weight of adipose tissues including mesenteric, epididymal, subcutaneous, and brown fat without any change in body weight, which was accompanied by abnormalities in adipose tissue functions such as fat storage and adiponectin production. Transplantation of colitis-induced altered microbiota also disrupted hepatic lipid metabolism in the GF recipient mice, which was observed by increases in synthesis and accumulation of cholesterol and bile acids in hepatocytes and a decrease in plasma HDL-cholesterol. Additional observations including elevated plasma levels of insulin, decreased hepatic production of FGF21, and decreased levels of fecal short chain fatty acids (SCFAs) and hepatic expression of SCFA receptors led to a conclusion that the transplantation of the colitis-associated dysbiotic microbiota was causally associated with impairments of insulin action and FGF21-adiponectin axis, possibly due to the low SCFA-producing capacity of the colonized microbiota, leading to metabolic abnormalities including adipose tissue dysfunction and dysregulated hepatic lipid metabolism. Our findings suggest potential mechanisms that explain how colitis-associated gut dysbiosis may contribute to the development of metabolic dysfunctions, which could be applied to clinical practice to improve the efficacy of treatment of IBD patients with comorbid metabolic disorders or vice versa.}, }
@article {pmid36732497, year = {2023}, author = {Xu, Y and Wang, J and Wu, X and Jing, H and Zhang, S and Hu, Z and Rao, L and Chang, Q and Wang, L and Zhang, Z}, title = {Gut microbiota alteration after cholecystectomy contributes to post-cholecystectomy diarrhea via bile acids stimulating colonic serotonin.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2168101}, pmid = {36732497}, issn = {1949-0984}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Serotonin ; Bile Acids and Salts/metabolism ; Colon/metabolism ; Diarrhea/drug therapy/metabolism ; Cholecystectomy ; }, abstract = {Post-cholecystectomy diarrhea (PCD) is highly prevalent among outpatients with cholecystectomy, and gut microbiota alteration is correlated with it. However, how and to what extent changed fecal bacteria contributes to diarrhea are still unrevealed. Humanized gut microbiome mice model by fecal microbiota transplantation was established to explore the diarrhea-inducible effects of gut microbiota. The role of microbial bile acids (BAs) metabolites was identified by UPLC/MS and the underlying mechanisms were investigated with selective inhibitors and antagonists as probes. These mice transplanted with fecal microbiome of PCD patients (PCD mice) exhibited significantly enhanced gastrointestinal motility and elevated fecal water content, compared with these mice with fecal microbiome of NonPCD patients and HC. In analyzing gut microbiota, tryptophan metabolism was enriched in PCD microbiome. In addition, overabundant serotonin in serum and colon, along with elevated biosynthesis gene and reduced reuptake gene, and highly expressed 5-HT receptors (5-HTRs) in colon of PCD mice were found, but not in small intestine. Notably, diarrheal phenotypes in PCD mice were depleted by tryptophan hydroxylase 1 inhibitor (LX1606) and 5-HTRs selective antagonists (alosetron and GR113808). Furthermore, increased microbial secondary BAs metabolites of DCA, HDCA and LCA were revealed in feces of PCD mice and they were found responsible for stimulating 5-HT level in vitro and in vivo. Intriguingly, blocking BAs-conjugated TGR5/TRPA1 signaling pathway could significantly alleviate PCD. In conclusion, altered gut microbiota after cholecystectomy contributes to PCD by promoting secondary BAs in colon, which stimulates colonic 5-HT and increases colon motility.}, }
@article {pmid36732495, year = {2023}, author = {Dong, TS and Katzka, W and Yang, JC and Chang, C and Arias-Jayo, N and Lagishetty, V and Balioukova, A and Chen, Y and Dutson, E and Li, Z and Mayer, EA and Pisegna, JR and Sanmiguel, C and Jacobs, JP}, title = {Microbial changes from bariatric surgery alters glucose-dependent insulinotropic polypeptide and prevents fatty liver disease.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2167170}, pmid = {36732495}, issn = {1949-0984}, support = {IK2 CX001717/CX/CSRD VA/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; R01 DK048351/DK/NIDDK NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Non-alcoholic Fatty Liver Disease/prevention &amp; control/complications ; *Obesity, Morbid/surgery ; *Gastrointestinal Microbiome ; *Bariatric Surgery ; Obesity/surgery/complications ; Receptors, G-Protein-Coupled ; Peptides ; Glucose ; }, abstract = {Bariatric surgery remains a potent therapy for nonalcoholic fatty liver disease (NAFLD), but its inherent risk and eligibility requirement limit its adoption. Therefore, understanding how bariatric surgery improves NAFLD is paramount to developing novel therapeutics. Here, we show that the microbiome changes induced by sleeve gastrectomy (SG) reduce glucose-dependent insulinotropic polypeptide (GIP) signaling and confer resistance against diet-induced obesity (DIO) and NAFLD. We examined a cohort of NALFD patients undergoing SG and evaluated their microbiome, serum metabolites, and GI hormones. We observed significant changes in Bacteroides, lipid-related metabolites, and reduction in GIP. To examine if the changes in the microbiome were causally related to NAFLD, we performed fecal microbial transplants in antibiotic-treated mice from patients before and after their surgery who had significant weight loss and improvement of their NAFLD. Mice transplanted with the microbiome of patients after bariatric surgery were more resistant to DIO and NAFLD development compared to mice transplanted with the microbiome of patients before surgery. This resistance to DIO and NAFLD was also associated with a reduction in GIP levels in mice with post-bariatric microbiome. We further show that the reduction in GIP was related to higher levels of Akkermansia and differing levels of indolepropionate, bacteria-derived tryptophan-related metabolite. Overall, this is one of the few studies showing that GIP signaling is altered by the gut microbiome, and it supports that the positive effect of bariatric surgery on NAFLD is in part due to microbiome changes.}, }
@article {pmid36730049, year = {2023}, author = {Bolia, R}, title = {Transanal Irrigation in Children With Functional Constipation: Doing It the Right Way for the Right Indication.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {76}, number = {3}, pages = {e67}, doi = {10.1097/MPG.0000000000003676}, pmid = {36730049}, issn = {1536-4801}, mesh = {Humans ; Child ; *Constipation/therapy ; Treatment Outcome ; Therapeutic Irrigation ; *Fecal Incontinence ; Anal Canal ; }, }
@article {pmid36728562, year = {2023}, author = {Yang, W and Ren, D and Shao, H and Zhang, X and Li, T and Zhang, L and Liu, L and Zhao, Y and Niu, P and Yang, X}, title = {Theabrownin from Fu Brick Tea Improves Ulcerative Colitis by Shaping the Gut Microbiota and Modulating the Tryptophan Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {6}, pages = {2898-2913}, doi = {10.1021/acs.jafc.2c06821}, pmid = {36728562}, issn = {1520-5118}, mesh = {Animals ; Mice ; *Colitis ; *Colitis, Ulcerative/drug therapy ; Colon ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Fluorouracil ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; Tea ; Tryptophan ; }, abstract = {Fu brick tea theabrownin (FBTB) is a kind of biomacromolecule produced by oxidative polymerization of tea polyphenols. Although a variety of diseases can be alleviated by TB, its ability to treat ulcerative colitis (UC) is still worth exploring. A dextran sulfate sodium (DSS)-induced chronic UC mouse model was designed to first explore the alleviatory effect of FBTB on UC and its underlying mechanism by the sequencing of fecal 16S rRNA genes, metabolomics, and fecal microbiota transplantation (FMT). Administration of FBTB at 400 mg/kg bw in DSS-damaged mice could effectively reduce colonic damage and inflammation and improve colonic antioxidant capacity to relieve the UC-caused symptoms. FBTB could correct the disrupted gut microbiota caused by UC and contribute to the proliferation of Lactobacillus and Parasutterella. FMT in combination with antibiotic treatment showed that FBTB could elevate the levels of microbial tryptophan metabolites, including indole-3-acetaldehyde (IAld) and indole-3-acetic acid (IAA), by selectively promoting the growth of Lactobacillus. Importantly, FBTB-elevated IAld and IAA could activate aromatic hydrocarbon receptors (AhRs) and enhance interleukin-22 production to repair the intestinal barrier. These findings demonstrated that FBTB alleviated UC mainly by targeting the gut microbiota involved in the AhR pathway for prophylactic and therapeutic treatment of UC.}, }
@article {pmid36726574, year = {2022}, author = {Han, TR and Yang, WJ and Tan, QH and Bai, S and Zhong, H and Tai, Y and Tong, H}, title = {Gut microbiota therapy for nonalcoholic fatty liver disease: Evidence from randomized clinical trials.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1004911}, pmid = {36726574}, issn = {1664-302X}, abstract = {Nonalcoholic fatty liver disease (NAFLD) has a high prevalence worldwide, but there are no medications approved for treatment. Gut microbiota would be a novel and promising therapeutic target based on the concept of the gut-liver axis in liver disease. We reviewed randomized controlled trials on gut microbiota therapy in NAFLD in this study to evaluate its efficacy and plausibility in NAFLD.}, }
@article {pmid36725289, year = {2023}, author = {Zhao, Q and Hao, Y and Yang, XQ and Yan, XY and Qiu, YL}, title = {[Preliminary study on the effect of fecal microbiota transplantation on neurobehavior and gut microbiota of offspring rats exposed to arsenic].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {41}, number = {1}, pages = {14-20}, doi = {10.3760/cma.j.cn121094-20220311-00125}, pmid = {36725289}, issn = {1001-9391}, support = {82103961//Youth Program of National Natural Science Foundation of China/ ; 81773405//National Natural Science Foundation of China/ ; 20210302124297//Free Exploration Youth Science Research Project of Shanxi/ ; }, mesh = {Male ; Rats ; Animals ; Female ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Arsenic ; Rats, Sprague-Dawley ; Feces ; }, abstract = {Objective: To explore the effects of fecal microbiota transplantation (FMT) on neurobehavior and gut microbiota of arsenic-exposed offspring rats. Methods: In April 2021, Thirty-six SPF SD rats aged 8 weeks were seleted, rats were ranked by weight and divided into four groups according to randomized block design, namely control group, arsenic exposure group (As group) , arsenic+normal saline group (As+NaCl group) and As+FMT group, 6 females and 3 males in each group. Fecal microbiota fluid were provided by feces of rats in control group. Rats drank tap water containing 75 mg/L sodium arsenite for one week and then were caged together. The arsenic exposure was terminated until the pups were born. Female rats with vaginal plug were treated with fecal microbiota fluid via gavage during neurodevelopmental teratogenic window period. The volume of gavage was 1 ml/100 g with once every two days, for a total of three times. Weight alterations of offspring rats were recorded every week after weaning, and when offspring rats grew up for 6 weeks, Morris test and open field experiment was used to observe learning and memory abilities, as well as neurobehavioral performance of autonomous exploration and tension, respectively. 16S rDNA sequencing technology was used to detect microbiota diversities in fecal samples of rats in As group and As+FMT group. Results: Compared with the control group, the ratio of swimming distance and staying time in the target quadrant and the times of crossing the platform of rats in As group decreased significantly, and the motor distance, times entering central zone and the number of grid crossing of rats decreased significantly (P<0.05) . Compared with As group, the ratio of swimming distance in target quadrant, the motor distance in central zone and times entering central zone of rats in As+FMT group were evidently increased (P<0.05) . The analysis of fecal microbiota diversities showed that, at the phyla level, the relative abundance of Bacteroidetes in feces of rats in As+FMT group was higher than that in As group (68.34% vs 60.55%) , while the relative abundance of Firmicutes was lower than that in As group (28.02% vs 33.48%) . At the genus level, the relative abundance of Prevotella in As+FMT group was significantly higher than that in As group, becoming the dominant genus (42.08% vs 21.78%) . Additionally, compared with As group, a total of 22 genus were increased with 21 decreased genus in As+FMT group (P<0.05) . LEfSe analysis showed that dominant genuses in As+FMT group were Prevotella and UCG_005, and their relative abundance was significantly higher than that of As group (P<0.05) . Conclusion: FMT may alleviate the impaired learning and memory ability and anxiety like behavior of the offspring rats exposed to arsenic, and improve the disrupted gut microbiota.}, }
@article {pmid36725206, year = {2023}, author = {Peng, Y and Dong, W and Chen, G and Mi, J and Lu, L and Xie, Z and Xu, W and Zhou, W and Sun, Y and Zeng, X and Cao, Y and Yan, Y}, title = {Anthocyanins from Lycium ruthenicum Murray Ameliorated High-Fructose Diet-Induced Neuroinflammation through the Promotion of the Integrity of the Intestinal Barrier and the Proliferation of Lactobacillus.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {6}, pages = {2864-2882}, doi = {10.1021/acs.jafc.2c06713}, pmid = {36725206}, issn = {1520-5118}, mesh = {Animals ; Mice ; *Anthocyanins ; Cell Proliferation ; Diet ; Dysbiosis/drug therapy/etiology/metabolism ; Fructose ; Lactobacillus ; *Lycium ; Mice, Inbred C57BL ; Neuroinflammatory Diseases ; Toll-Like Receptor 4 ; }, abstract = {In the present study, we found that anthocyanins from Lycium ruthenicum Murray (ACN) potently ameliorated a high-fructose diet (HFrD)-induced neuroinflammation in mice. ACN improved the integrity of the intestinal barrier and suppressed the toll-like receptor 4 (TLR4) signaling pathway to ameliorate the neuroinflammation, which was verified by Tlr4[-/-] mice. Furthermore, ACN could modulate the HFrD-induced dysbiosis of gut microbiota. The fecal microbiota transplantation from ACN-induced mice was sufficient to attenuate the neuroinflammation, while the amelioration of neuroinflammation by ACN was blocked upon gut microbiota depletion. In addition, ACN-induced increment of the relative abundance of Lactobacillus might be responsible for the alleviation of the neuroinflammation, which was further confirmed in the promoting effect of ACN on the growth of Lactobacillus in vitro. Overall, these results provided the evidence of a comprehensive cross-talk mechanism between ACN and neuroinflammation in HFrD-fed mice, which was mediated by reducing gut microbiota dysbiosis and maintaining the intestinal barrier integrity.}, }
@article {pmid36722516, year = {2023}, author = {Kwa, WT and Sundarajoo, S and Toh, KY and Lee, J}, title = {Application of emerging technologies for gut microbiome research.}, journal = {Singapore medical journal}, volume = {64}, number = {1}, pages = {45-52}, pmid = {36722516}, issn = {2737-5935}, mesh = {Humans ; *Gastrointestinal Microbiome ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Health Status ; }, abstract = {Microbiome is associated with a wide range of diseases. The gut microbiome is also a dynamic reflection of health status, which can be modified, thus representing great potential to exploit the mechanisms that influence human physiology. Recent years have seen a dramatic rise in gut microbiome studies, which has been enabled by the rapidly evolving high-throughput sequencing methods (i.e. 16S rRNA sequencing and shotgun sequencing). As the emerging technologies for microbiome research continue to evolve (i.e. metatranscriptomics, metabolomics, culturomics, synthetic biology), microbiome research has moved beyond phylogenetic descriptions and towards mechanistic analyses. In this review, we highlight different approaches to study the microbiome, in particular, the current limitations and future promise of these techniques. This review aims to provide clinicians with a framework for studying the microbiome, as well as to accelerate the adoption of these techniques in clinical practice.}, }
@article {pmid36721210, year = {2023}, author = {Pi, Y and Wu, Y and Zhang, X and Lu, D and Han, D and Zhao, J and Zheng, X and Zhang, S and Ye, H and Lian, S and Bai, Y and Wang, Z and Tao, S and Ni, D and Zou, X and Jia, W and Zhang, G and Li, D and Wang, J}, title = {Gut microbiota-derived ursodeoxycholic acid alleviates low birth weight-induced colonic inflammation by enhancing M2 macrophage polarization.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {19}, pmid = {36721210}, issn = {2049-2618}, mesh = {Swine ; Animals ; Mice ; *Gastrointestinal Microbiome ; Ursodeoxycholic Acid ; Birth Weight ; Dysbiosis/drug therapy ; Inflammation/drug therapy ; *Colitis ; Disease Models, Animal ; }, abstract = {BACKGROUND: Low birth weight (LBW) is associated with intestinal inflammation and dysbiosis after birth. However, the underlying mechanism remains largely unknown.<br><br>OBJECTIVE: In the present study, we aimed to investigate the metabolism, therapeutic potential, and mechanisms of action of bile acids (BAs) in LBW-induced intestinal inflammation in a piglet model.<br><br>METHODS: The fecal microbiome and BA profile between LBW and normal birth weight (NBW) neonatal piglets were compared. Fecal microbiota transplantation (FMT) was employed to further confirm the linkage between microbial BA metabolism and intestinal inflammation. The therapeutic potential of ursodeoxycholic acid (UDCA), a highly differentially abundant BA between LBW and NBW piglets, in alleviating colonic inflammation was evaluated in both LBW piglets, an LBW-FMT mice model, and a DSS-induced colitis mouse model. The underlying cellular and molecular mechanisms by which UDCA suppresses intestinal inflammation were also investigated in both DSS-treated mice and a macrophage cell line. Microbiomes were analyzed by using 16S ribosomal RNA sequencing. Fecal and intestinal BA profiles were measured by using targeted BA metabolomics. Levels of farnesoid X receptor (FXR) were knocked down in J774A.1 cells with small interfering RNAs.<br><br>RESULTS: We show a significant difference in both the fecal microbiome and BA profiles between LBW and normal birth weight animals in a piglet model. Transplantation of the microbiota of LBW piglets to antibiotic-treated mice leads to intestinal inflammation. Importantly, oral administration of UDCA, a major BA diminished in the intestinal tract of LBW piglets, markedly alleviates intestinal inflammation in LBW piglets, an LBW-FMT mice model, and a mouse model of colitis by inducing M2 macrophage polarization. Mechanistically, UDCA reduces inflammatory cytokine production by engaging BA receptor FXR while suppressing NF-&#x3ba;B activation in macrophages.<br><br>CONCLUSIONS: These findings establish a causal relationship between LBW-associated intestinal abnormalities and dysbiosis, suggesting that restoring intestinal health and postnatal maldevelopment of LBW infants may be achieved by targeting intestinal microbiota and BA metabolism. Video Abstract.}, }
@article {pmid36721179, year = {2023}, author = {Wang, X and Wang, Z and Cao, J and Dong, Y and Chen, Y}, title = {Gut microbiota-derived metabolites mediate the neuroprotective effect of melatonin in cognitive impairment induced by sleep deprivation.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {17}, pmid = {36721179}, issn = {2049-2618}, mesh = {Animals ; Mice ; Sleep Deprivation/drug therapy ; *Gastrointestinal Microbiome ; *Melatonin/pharmacology/therapeutic use ; *Neuroprotective Agents ; Lipopolysaccharides ; Toll-Like Receptor 4 ; Butyrates ; Clostridiales ; *Cognitive Dysfunction/drug therapy ; }, abstract = {Sleep loss is a serious global health concern. Consequences include memory deficits and gastrointestinal dysfunction. Our previous research showed that melatonin can effectively improve cognitive impairment and intestinal microbiota disturbances caused by sleep deprivation (SD). The present study further explored the mechanism by which exogenous melatonin prevents SD-induced cognitive impairments. Here, we established fecal microbiota transplantation, Aeromonas colonization and LPS or butyrate supplementation tests to evaluate the role of the intestinal microbiota and its metabolites in melatonin in alleviating SD-induced memory impairment. RESULTS: Transplantation of the SD-gut microbiota into normal mice induced microglia overactivation and neuronal apoptosis in the hippocampus, cognitive decline, and colonic microbiota disorder, manifesting as increased levels of Aeromonas and LPS and decreased levels of Lachnospiraceae_NK4A136 and butyrate. All these events were reversed with the transplantation of SD + melatonin-gut microbiota. Colonization with Aeromonas and the addition of LPS produced an inflammatory response in the hippocampus and spatial memory impairment in mice. These changes were reversed by supplementation with melatonin, accompanied by decreased levels of Aeromonas and LPS. Butyrate administration to sleep-deprived mice restored inflammatory responses and memory impairment. In vitro, LPS supplementation caused an inflammatory response in BV2 cells, which was improved by butyrate supplementation. This ameliorative effect of butyrate was blocked by pretreatment with MCT1 inhibitor and HDAC3 agonist but was mimicked by TLR4 and p-P65 antagonists. CONCLUSIONS: Gut microbes and their metabolites mediate the ameliorative effects of melatonin on SD-induced cognitive impairment. A feasible mechanism is that melatonin downregulates the levels of Aeromonas and constituent LPS and upregulates the levels of Lachnospiraceae_NK4A136 and butyrate in the colon. These changes lessen the inflammatory response and neuronal apoptosis in the hippocampus through crosstalk between the TLR4/NF-κB and MCT1/ HDAC3 signaling pathways. Video Abstract.}, }
@article {pmid36720452, year = {2023}, author = {Yang, JZ and Zhang, KK and He, JT and Chen, LJ and Ding, JF and Liu, JL and Li, JH and Liu, Y and Li, XW and Zhao, D and Xie, XL and Wang, Q}, title = {Obeticholic acid protects against methamphetamine-induced anxiety-like behavior by ameliorating microbiota-mediated intestinal barrier impairment.}, journal = {Toxicology}, volume = {486}, number = {}, pages = {153447}, doi = {10.1016/j.tox.2023.153447}, pmid = {36720452}, issn = {1879-3185}, mesh = {Mice ; Animals ; *Methamphetamine/toxicity ; Neuroinflammatory Diseases ; *Microbiota ; Anxiety/chemically induced/prevention &amp; control ; }, abstract = {Methamphetamine (Meth) abuse can cause severe anxiety disorder and interfere with gut homeostasis. Obeticholic acid (OCA) has emerged as a protective agent against diet-related anxiety that improves gut homeostasis. The potential for OCA to ameliorate Meth-induced anxiety, and the microbial mechanisms involved, remain obscure. Here, C57/BL6 mice were intraperitoneally injected with Meth (15 mg/kg) to induce anxiety-like behavior. 16 S rRNA sequence analysis and fecal microbiome transplantation (FMT) were used to profile the gut microbiome and evaluate its effects, respectively. Orally administered OCA was investigated for protection against Meth-induced anxiety. Results indicated that Meth mediated anxiety-like behavior, aroused hippocampal neuroinflammation through activation of the TLR4/MyD88/NF-κB pathway, weakened intestinal barrier and disturbed the gut microbiome. Specifically, abundance of anxiety-related Rikenella was increased. FMT from Meth-administrated mice also weakened intestinal barrier and elevated serum LPS, inducing hippocampal neuroinflammation and anxiety-like behavior in recipient mice. Finally, OCA pretreatment ameliorated Meth-induced impairment of gut homeostasis by reshaping the microbial composition and improving the intestinal barrier. Meth-induced anxiety-like behavior and hippocampal neuroinflammation were also ameliorated by OCA pretreatment. These preliminary findings reveal the crucial role of gut microbiota in Meth-induced anxiety-like behavior and neuroinflammation, highlighting OCA as a potential candidate for the prevention of Meth-induced anxiety.}, }
@article {pmid36720105, year = {2023}, author = {Conover, KR and Absah, I and Ballal, S and Brumbaugh, D and Cho, S and Cardenas, MC and Knackstedt, ED and Goyal, A and Jensen, MK and Kaplan, JL and Kellermayer, R and Kociolek, LK and Michail, S and Oliva-Hemker, M and Reed, AW and Weatherly, M and Kahn, SA and Nicholson, MR}, title = {Fecal Microbiota Transplantation for Clostridioides difficile Infection in Immunocompromised Pediatric Patients.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {76}, number = {4}, pages = {440-446}, pmid = {36720105}, issn = {1536-4801}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; UL1 TR000445/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Humans ; Child ; Adolescent ; Fecal Microbiota Transplantation/adverse effects ; Retrospective Studies ; *Clostridioides difficile ; Treatment Outcome ; Recurrence ; *Clostridium Infections/therapy ; }, abstract = {OBJECTIVES: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients.<br><br>METHODS: This is a multicenter retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow-up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition.<br><br>RESULTS: Of 59 pediatric patients identified at 9 centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after 1 or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; 4 (9.5%) of which were likely treatment-related. There were no deaths or infections with multidrug resistant organisms during follow-up and all patients with a SAE fully recovered.<br><br>CONCLUSIONS: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit.}, }
@article {pmid36719820, year = {2023}, author = {Rokkas, T and Hold, GL}, title = {A systematic review, pairwise meta-analysis and network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in irritable bowel syndrome.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {35}, number = {4}, pages = {471-479}, doi = {10.1097/MEG.0000000000002519}, pmid = {36719820}, issn = {1473-5687}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Irritable Bowel Syndrome/therapy ; Network Meta-Analysis ; Randomized Controlled Trials as Topic ; Duodenoscopy ; Treatment Outcome ; Feces ; }, abstract = {BACKGROUND: Treatment is a challenge in Irritable Bowel Syndrome (IBS) and fecal microbiota transplantation (FMT) has attracted significant interest. Network meta-analysis (NWM) has been established as an evidence-synthesis tool that incorporates direct and indirect evidence in a collection of randomized controlled trials (RCTs) comparing therapeutic intervention competing for similar therapeutic results. No NWM exists concerning the comparative effectiveness and safety of various FMT modalities for IBS.<br><br>AIM: We updated pairwise meta-analyses published in the past and assessed the comparative effectiveness and safety of various FMT delivery modalities for IBS.<br><br>METHODS: Pairwise meta-analyses and Bayesian NWM were performed. Heterogeneity, consistency of results and publication bias were explored.<br><br>RESULTS: Of 510 titles raised by initial search, seven RCTs were entered into meta-analyses and NWM. They included 470 patients and controls, in whom four FMT delivery modalities were used, that is via colonoscopy, nasojejunal tube, duodenoscope and capsules per os. In the pairwise meta-analysis, the pooled results showed that overall FMT was not superior to placebo, whereas the subgroup analyses showed that FMT via duodenoscope and nasojejunal tube was superior. The NWM showed that 60-g FMT via duodenoscope had the highest efficacy (OR, 26.38; 95% CI, 9.22-75.51) and was by far the highest in the efficacy ranking (SUCRA, 98.8%).<br><br>CONCLUSION: The pooled results showed no overall advantage of FMT over placebo in IBS. However, upper GI delivery (via duodenoscopy or nasojejunal tube) proved to be effective. Consequently, well-designed RCTs are needed to ensure the efficacy and safety profile before FMT can be applied in everyday clinical practice for IBS patients.}, }
@article {pmid36717922, year = {2023}, author = {Xu, QQ and Su, ZR and Yang, W and Zhong, M and Xian, YF and Lin, ZX}, title = {Patchouli alcohol attenuates the cognitive deficits in a transgenic mouse model of Alzheimer's disease via modulating neuropathology and gut microbiota through suppressing C/EBPβ/AEP pathway.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {19}, pmid = {36717922}, issn = {1742-2094}, support = {82104414//National Natural Science Foundation of China/ ; 2019A1515011257//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Humans ; Mice ; Animals ; *Alzheimer Disease/therapy/drug therapy ; Mice, Transgenic ; tau Proteins/metabolism ; *Gastrointestinal Microbiome ; Neuroinflammatory Diseases ; Activities of Daily Living ; Dysbiosis ; *Neurodegenerative Diseases ; *Cognitive Dysfunction/metabolism ; Amyloid beta-Protein Precursor/genetics/metabolism ; Amyloid beta-Peptides/metabolism ; Cognition ; Disease Models, Animal ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive cognitive dysfunctions and behavioral impairments. Patchouli alcohol (PA), isolated from Pogostemonis Herba, exhibits multiple pharmacological properties, including neuroprotective effects. This study aimed to investigate the therapeutic effects of PA against AD using the TgCRND8 transgenic AD mouse model, and to explore the underlying mechanisms targeting CCAAT/enhancer-binding protein β/asparagine endopeptidase (C/EBPβ/AEP) signaling pathway.<br><br>METHODS: After genotyping to confirm the transgenicity, drug treatments were administered intragastrically once daily to 3-month-old TgCRND8 mice for 4 consecutive months. Several behavioral tests were applied to assess different aspects of neurological functions. Then the brain and colon tissues were harvested for in-depth mechanistic studies. To further verify whether PA exerts anti-AD effects via modulating C/EBP&#x3b2;/AEP signaling pathway in TgCRND8 mice, adeno-associated virus (AAV) vectors encoding CEBP/&#x3b2; were bilaterally injected into the hippocampal CA1 region in TgCRND8 mice to overexpress C/EBP&#x3b2;. Additionally, the fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of gut microbiota on the anti-AD effects of PA.<br><br>RESULTS: Our results showed that PA treatment significantly improved activities of daily living (ADL), ameliorated the anxiety-related behavioral deficits and cognitive impairments in TgCRND8 mice. PA modulated the amyloid precursor protein (APP) processing. PA also markedly reduced the levels of beta-amyloid (A&#x3b2;) 40 and A&#x3b2;42, suppressed A&#x3b2; plaque burdens, inhibited tau protein hyperphosphorylation at several sites and relieved neuroinflammation in the brains of TgCRND8 mice. Moreover, PA restored gut dysbiosis and inhibited the activation of the C/EBP&#x3b2;/AEP signaling pathway in the brain and colon tissues of TgCRND8 mice. Interestingly, PA strikingly alleviated the AD-like pathologies induced by the overexpression of C/EBP&#x3b2; in TgCRND8 mice. Additionally, the FMT of fecal microbiota from the PA-treated TgCRND8 mice significantly alleviated the cognitive impairments and AD-like pathologies in the germ-free TgCRND8 mice.<br><br>CONCLUSION: All these findings amply demonstrated that PA could ameliorate the cognitive deficits in TgCRND8 mice via suppressing A&#x3b2; plaques deposition, hyperphosphorylation of tau protein, neuroinflammation and gut dysbiosis through inhibiting the activation of C/EBP&#x3b2;/AEP pathway, suggesting that PA is a promising naturally occurring chemical worthy of further development into the pharmaceutical treatment of AD.}, }
@article {pmid36717576, year = {2023}, author = {Sun, WL and Hua, S and Li, XY and Shen, L and Wu, H and Ji, HF}, title = {Microbially produced vitamin B12 contributes to the lipid-lowering effect of silymarin.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {477}, pmid = {36717576}, issn = {2041-1723}, mesh = {Humans ; Rats ; Male ; Mice ; Animals ; *Silymarin/pharmacology/metabolism ; Vitamin B 12/pharmacology/metabolism ; Antioxidants/metabolism ; Liver/metabolism ; Lipid Metabolism ; Lipids/pharmacology ; }, abstract = {Silymarin has been used for improving hepatic damage and lipid disorders, but its action mechanism remains to be clarified. Here, we investigate the contributions of the gut microbiota to the improvement of liver lipid metabolism by silymarin. We find i) strong and significant microbial shifts upon silymarin but not silibinin treatment; ii) over 60% variations of liver fat are explained by silymarin-induced bacterial B12 production in male rats but not in male germ-free mice; iii) fecal microbiota transplantation confirms their protective roles against liver fat accumulation; iv) upregulation of one-carbon metabolism and fatty acid degradation pathways are observed based on the liver transcriptome analyses; and v) in humans the delta changes of serum B12 associate negatively with the fluctuations of serum triglycerides. Overall, we reveal a mechanism of action underpinning the lipid-lowering effect of silymarin via the gut microbiota and its vitamin B12 producing capabilities.}, }
@article {pmid36717202, year = {2023}, author = {}, title = {Early use of faecal microbiota transplantation for C. difficile infection.}, journal = {Drug and therapeutics bulletin}, volume = {61}, number = {3}, pages = {36}, doi = {10.1136/dtb.2023.000003}, pmid = {36717202}, issn = {1755-5248}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridioides difficile ; Feces ; *Clostridium Infections ; Double-Blind Method ; }, abstract = {Overview of: Baunwall SMD, Andreasen SE, Hansen MM, et al Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol 2022;7:1083-91.}, }
@article {pmid36714122, year = {2022}, author = {Hocking, L and Wilcox, M and Petrosillo, N and Griffin, P and Steiner, T and Attara, G and Doré, J and Cabling, M and Stockwell, S and Romanelli, RJ and Marjanovic, S}, title = {Improving care for patients with Clostridioides difficile infection: A clinical practice and healthcare systems perspective.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1033417}, pmid = {36714122}, issn = {2296-858X}, abstract = {INTRODUCTION: Arriving at a C. difficile infection (CDI) diagnosis, treating patients and dealing with recurrences is not straightforward, but a comprehensive and well-rounded understanding of what is needed to improve patient care is lacking. This manuscript addresses the paucity of multidisciplinary perspectives that consider clinical practice related and healthcare system-related challenges to optimizing care delivery.<br><br>METHODS: We draw on narrative review, consultations with clinical experts and patient representatives, and a survey of 95 clinical and microbiology experts from the UK, France, Italy, Australia and Canada, adding novel multi-method evidence to the knowledge base.<br><br>RESULTS AND DISCUSSION: We examine the patient pathway and variations in clinical practice and identify, synthesize insights on and discuss associated challenges. Examples of key challenges include the need to conduct multiple tests for a conclusive diagnosis, treatment side-effects, the cost of some antibiotics and barriers to access of fecal microbiota transplantation, difficulties in distinguishing recurrence from new infection, workforce capacity constraints to effective monitoring of patients on treatment and of recurrence, and ascertaining whether a patient has been cured. We also identify key opportunities and priorities for improving patient care that target both clinical practice and the wider healthcare system. While there is some variety across surveyed countries' healthcare systems, there is also strong agreement on some priorities. Key improvement actions seen as priorities by at least half of survey respondents in at least three of the five surveyed countries include: developing innovative products for both preventing (Canada, Australia, UK, Italy, and France) and treating (Canada, Australia, and Italy) recurrences; facilitating more multidisciplinary patient care (UK, Australia, and France); updating diagnosis and treatment guidelines (Australia, Canada, and UK); and educating and supporting professionals in primary care (Italy, UK, Canada, and Australia) and those in secondary care who are not CDI experts (Italy, Australia, and France) on identifying symptoms and managing patients. Finally, we discuss key evidence gaps for a future research agenda.}, }
@article {pmid36714101, year = {2022}, author = {Tkach, S and Dorofeyev, A and Kuzenko, I and Falalyeyeva, T and Tsyryuk, O and Kovalchuk, O and Kobyliak, N and Abenavoli, L and Boccuto, L}, title = {Efficacy and safety of fecal microbiota transplantation via colonoscopy as add-on therapy in patients with mild-to-moderate ulcerative colitis: A randomized clinical trial.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1049849}, pmid = {36714101}, issn = {2296-858X}, abstract = {INTRODUCTION: Growing evidence supports the effectiveness of fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), although its effects seem to depend on the method of introduction, the number of procedures, the donor material, and the severity of UC.<br><br>AIM: This study aimed to assess FMT's clinical and microbiological efficacy, tolerability, and safety in patients with mild-to-moderate UC.<br><br>MATERIAL AND METHODS: Patients with mild-to-moderate UC were randomized into two groups. The first group (standard-care, n = 27) was treated with basic therapy-mesalazine-at a daily dose of 3 g (2 g orally + 1 g rectally). In the second group (FMT group, n = 26), while taking mesalazine at the indicated dose, each patient with UC as add-on therapy underwent a single FMT procedure with fresh material delivered by colonoscopy from a healthy donor. The clinical efficacy of treatment in both groups was evaluated after 4 and 8 weeks. The primary outcome was remission of UC, defined as a partial Mayo score &#x2264;2, and decreased fecal calprotectin. All patients underwent bacteriological examination of feces for quantitative microbiota composition changes.<br><br>RESULTS: Clinical response in the form of a significant decrease in stool frequency and a tendency to normalize its consistency after 4 weeks was detected in 14 (51.9%) patients of the standard care group and 16 patients (61.5%) of the FMT group (p = 0.583). The Mayo score in the standard care group was 3.59 &#xb1; 1.21 and in the FMT group-3.15&#xb1;1.04 (p=0.166). After 8 weeks, the main primary endpoint was achieved in 70.4% of the standard-care group patients as compared to 84.6% of participants who received FMT as add-on therapy (p = 0.215). A more pronounced decrease in Mayo score was observed in the FMT group compared to the standard-care group (1.34 &#xb1; 1.44 vs. 2.14 &#xb1; 1.4; p = 0.045). All patients also showed a significant decrease in fecal calprotectin levels, which correlated with clinical data, stool frequency, and clinical remission. An improvement in gut microbiota composition was noted in both groups, albeit it was significantly more pronounced in the FMT group.<br><br>CONCLUSIONS: FTM in patients with mild-to-moderate UC is a well-tolerated, effective, and safe method of treatment in comparison to basic therapy.<br><br>CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT05538026?term=kobyliak&amp;draw=2&amp;rank=4, identifier: NCT05538026.}, }
@article {pmid36713461, year = {2022}, author = {Lou, X and Xue, J and Shao, R and Yang, Y and Ning, D and Mo, C and Wang, F and Chen, G}, title = {Fecal microbiota transplantation and short-chain fatty acids reduce sepsis mortality by remodeling antibiotic-induced gut microbiota disturbances.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1063543}, pmid = {36713461}, issn = {1664-3224}, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; RNA, Ribosomal, 16S/genetics ; Anti-Bacterial Agents/therapeutic use ; *Sepsis/therapy/microbiology ; Fatty Acids, Volatile ; }, abstract = {OBJECTIVE: Sepsis is the leading cause of death in critically ill patients. The gastrointestinal tract has long been thought to play an important role in the pathophysiology of sepsis. Antibiotic therapy can reduce a patient's commensal bacterial population and raise their risk of developing subsequent illnesses, where gut microbiota dysbiosis may be a key factor.<br><br>METHODS: In this study, we analyzed the 16S rRNA of fecal samples from both healthy people and patients with sepsis to determine if alterations in gut bacteria are associated with sepsis. Then, we developed a mouse model of sepsis using cecal ligation and puncture (CLP) in order to examine the effects of fecal microbiota transplantation (FMT) and short-chain fatty acids (SCFAs) on survival rate, systemic inflammatory response, gut microbiota, and mucosal barrier function.<br><br>RESULTS: Sepsis patients' gut microbiota composition significantly differed from that of healthy people. At the phylum level, the amount of Proteobacteria in the intestinal flora of sepsis patients was much larger than that of the control group, whereas the number of Firmicutes was significantly lower. Mice with gut microbiota disorders (ANC group) were found to have an elevated risk of death, inflammation, and organ failure as compared to CLP mice. However, all of these could be reversed by FMT and SCFAs. FMT and SCFAs could regulate the abundance of bacteria such as Firmicutes, Proteobacteria, Escherichia Shigella, and Lactobacillus, restoring them to levels comparable to those of healthy mice. In addition, they increased the expression of the Occludin protein in the colon of mice with sepsis, downregulated the expression of the NLRP3 and GSDMD-N proteins, and reduced the release of the inflammatory factors IL-1&#x3b2; and IL-18 to inhibit cell pyroptosis, ultimately playing a protective role in sepsis.<br><br>DISCCUSION: FMT and SCFAs provide a microbe-related survival benefit in a mouse model of sepsis, suggesting that they may be a viable treatment for sepsis.}, }
@article {pmid36713428, year = {2022}, author = {Li, N and Xu, S and Zhang, S and Zhu, Q and Meng, X and An, W and Fu, B and Zhong, M and Yang, Y and Lin, Z and Liu, X and Xia, J and Wang, J and You, T and Yan, C and Tang, H and Zhuang, G and Peng, Z}, title = {MSI2 deficiency in ILC3s attenuates DSS-induced colitis by affecting the intestinal microbiota.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {963379}, pmid = {36713428}, issn = {1664-3224}, mesh = {Animals ; Mice ; Bacteria/genetics ; *Colitis/chemically induced/genetics/metabolism ; *Gastrointestinal Microbiome ; Immunity, Innate ; *Inflammatory Bowel Diseases/chemically induced/genetics ; Lymphocytes/metabolism ; RNA, Ribosomal, 16S/genetics ; *RNA-Binding Proteins/genetics ; }, abstract = {BACKGROUND: The etiology and pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are generally believed to be related to immune dysfunction and intestinal microbiota disorder. However, the exact mechanism is not yet fully understood. The pathological changes associated with dextran sodium sulfate (DSS)-induced colitis are similar to those in human UC. As a subgroup of the innate immune system, group 3 innate lymphoid cells (ILC3s) are widely distributed in the lamina propria of the intestinal mucosa, and their function can be regulated by a variety of molecules. Musashi2 (MSI2) is a type of evolutionarily conserved RNA-binding protein that maintains the function of various tissue stem cells and is essential for postintestinal epithelial regeneration. The effect of MSI2 deficiency in ILC3s on IBD has not been reported. Thus, mice with conditional MSI2 knockout in ILC3s were used to construct a DSS-induced colitis model and explore its effects on the pathogenesis of IBD and the species, quantity and function of the intestinal microbiota.<br><br>METHODS: Msi2[flox/flox] mice (Msi2[fl/fl]) and Msi2[flox/flox]Rorc[Cre] mice (Msi2[&#x394;Rorc]) were induced by DSS to establish the IBD model. The severity of colitis was evaluated by five measurements: body weight percentage, disease activity index, colon shortening degree, histopathological score and routine blood examination. The species, quantity and function of the intestinal microbiota were characterized by high-throughput 16S rRNA gene sequencing of DNA extracted from fecal samples.<br><br>RESULTS: MSI2 was knocked out in the ILC3s of Msi2[&#x394;Rorc] mice. The Msi2[&#x394;Rorc] mice exhibited reductions in body weight loss, the disease activity index, degree of colon shortening, tissue histopathological score and immune cells in the peripheral blood compared to those of Msi2[fl/fl] mice after DSS administration. The 16S rRNA sequencing results showed that the diversity of the intestinal microbiota in DSS-treated Msi2[&#x394;Rorc] mice changed, with the abundance of Firmicutes increasing and that of Bacteroidetes decreasing. The linear discriminant analysis effect size (LEfSe) approach revealed that Lactobacillaceae could be the key bacteria in the Msi2[&#x394;Rorc] mouse during the improvement of colitis. Using PICRUST2 to predict the function of the intestinal microbiota, it was found that the functions of differential bacteria inferred by modeling were mainly enriched in infectious diseases, immune system and metabolic functions.<br><br>CONCLUSIONS: MSI2 deficiency in ILC3s attenuated DSS-induced colonic inflammation in mice and affected intestinal microbiota diversity, composition, and function, with Lactobacillaceae belonging to the phylum Firmicutes possibly representing the key bacteria. This finding could contribute to our understanding of the pathogenesis of IBD and provide new insights for its clinical diagnosis and treatment.}, }
@article {pmid36713373, year = {2022}, author = {Jiang, L and Yuan, C and Ye, W and Huang, Q and Chen, Z and Wu, W and Qian, L}, title = {Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1061627}, pmid = {36713373}, issn = {1664-3224}, mesh = {Mice ; Animals ; Akkermansia ; *Campylobacter Infections/therapy ; In Situ Hybridization, Fluorescence ; RNA, Ribosomal, 16S ; Phosphatidylinositol 3-Kinases/genetics ; Proteomics ; Mice, Inbred C57BL ; *Colitis ; *Gastroenteritis ; Deoxycholic Acid ; Butyrates ; }, abstract = {INTRODUCTION: Campylobacter jejuni (C. jejuni) is a common food-borne bacterial pathogen that can use the host's innate immune response to induce the development of colitis. There has been some research on the role of normal intestinal flora in C. jejuni-induced colitis, but the mechanisms that play a central role in resistance to C. jejuni infection have not been explored.<br><br>METHODS: We treated Campylobacter jejuni-infected mice with fecal microbiota transplantation (FMT), oral butyric acid and deoxycholic acid in a controlled trial and analyzed the possible mechanisms of treatment by a combination of chromatography, immunohistochemistry, fluorescence in situ hybridization, 16s rRNA gene, proteomics and western blot techniques.<br><br>RESULTS: We first investigated the therapeutic effect of FMT on C. jejuni infection. The results showed that FMT significantly reduced the inflammatory response and blocked the invasion of C.jejuni into the colonic tissue. We observed a significant increase in the abundance of Akkermansia in the colon of mice after FMT, as well as a significant increase in the levels of butyric acid and deoxycholic acid. We next demonstrated that oral administration of sodium butyrate or deoxycholic acid had a similar therapeutic effect. Further proteomic analysis showed that C.jejuni induced colitis mainly through activation of the PI3K-AKT signaling pathway and MAPK signaling pathway, whereas Akkermansia, the core flora of FMT, and the gut microbial metabolites butyric acid and deoxycholic acid both inhibited these signaling pathways to counteract the infection of C. jejuni and alleviate colitis. Finally, we verified the above idea by in vitro cellular assays. In conclusion, FMT is highly effective in the treatment of colitis caused by C. jejuni, with which Akkermansia and butyric and deoxycholic acids are closely associated.The present study demonstrates that Akkermansia and butyric and deoxycholic acids are effective in the treatment of colitis caused by C. jejuni.<br><br>DISCUSSION: This is the first time that Akkermansia has been found to be effective in fighting pathogens, which provides new ideas and insights into the use of FMT to alleviate colitis caused by C. jejuni and Akkermansia as a treatment for intestinal sexually transmitted diseases caused by various pathogens.}, }
@article {pmid36713364, year = {2022}, author = {Alam, MZ and Maslanka, JR and Abt, MC}, title = {Immunological consequences of microbiome-based therapeutics.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1046472}, pmid = {36713364}, issn = {1664-3224}, support = {R01 AI130115/AI/NIAID NIH HHS/United States ; R01 AI158830/AI/NIAID NIH HHS/United States ; R21 AI164385/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Fecal Microbiota Transplantation ; Bacteria ; *Neoplasms ; Obesity ; }, abstract = {The complex network of microscopic organisms living on and within humans, collectively referred to as the microbiome, produce wide array of biologically active molecules that shape our health. Disruption of the microbiome is associated with susceptibility to a range of diseases such as cancer, diabetes, allergy, obesity, and infection. A new series of next-generation microbiome-based therapies are being developed to treat these diseases by transplanting bacteria or bacterial-derived byproducts into a diseased individual to reset the recipient's microbiome and restore health. Microbiome transplantation therapy is still in its early stages of being a routine treatment option and, with a few notable exceptions, has had limited success in clinical trials. In this review, we highlight the successes and challenges of implementing these therapies to treat disease with a focus on interactions between the immune system and microbiome-based therapeutics. The immune activation status of the microbiome transplant recipient prior to transplantation has an important role in supporting bacterial engraftment. Following engraftment, microbiome transplant derived signals can modulate immune function to ameliorate disease. As novel microbiome-based therapeutics are developed, consideration of how the transplants will interact with the immune system will be a key factor in determining whether the microbiome-based transplant elicits its intended therapeutic effect.}, }
@article {pmid36713166, year = {2022}, author = {Singh, V and Lee, G and Son, H and Koh, H and Kim, ES and Unno, T and Shin, JH}, title = {Butyrate producers, "The Sentinel of Gut": Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1103836}, pmid = {36713166}, issn = {1664-302X}, abstract = {Gut-microbial butyrate is a short-chain fatty acid (SCFA) of significant physiological importance than the other major SCFAs (acetate and propionate). Most butyrate producers belong to the Clostridium cluster of the phylum Firmicutes, such as Faecalibacterium, Roseburia, Eubacterium, Anaerostipes, Coprococcus, Subdoligranulum, and Anaerobutyricum. They metabolize carbohydrates via the butyryl-CoA: acetate CoA-transferase pathway and butyrate kinase terminal enzymes to produce most of butyrate. Although, in minor fractions, amino acids can also be utilized to generate butyrate via glutamate and lysine pathways. Butyrogenic microbes play a vital role in various gut-associated metabolisms. Butyrate is used by colonocytes to generate energy, stabilizes hypoxia-inducible factor to maintain the anaerobic environment in the gut, maintains gut barrier integrity by regulating Claudin-1 and synaptopodin expression, limits pro-inflammatory cytokines (IL-6, IL-12), and inhibits oncogenic pathways (Akt/ERK, Wnt, and TGF-β signaling). Colonic butyrate producers shape the gut microbial community by secreting various anti-microbial substances, such as cathelicidins, reuterin, and β-defensin-1, and maintain gut homeostasis by releasing anti-inflammatory molecules, such as IgA, vitamin B, and microbial anti-inflammatory molecules. Additionally, butyrate producers, such as Roseburia, produce anti-carcinogenic metabolites, such as shikimic acid and a precursor of conjugated linoleic acid. In this review, we summarized the significance of butyrate, critically examined the role and relevance of butyrate producers, and contextualized their importance as microbial therapeutics.}, }
@article {pmid36713033, year = {2023}, author = {Li, R and Liu, R and Chen, L and Wang, G and Qin, L and Yu, Z and Wan, Z}, title = {Microbiota from Exercise Mice Counteracts High-Fat High-Cholesterol Diet-Induced Cognitive Impairment in C57BL/6 Mice.}, journal = {Oxidative medicine and cellular longevity}, volume = {2023}, number = {}, pages = {2766250}, pmid = {36713033}, issn = {1942-0994}, mesh = {Animals ; Mice ; Cholesterol/pharmacology ; *Cognitive Dysfunction/therapy ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases ; RNA, Ribosomal, 16S ; Physical Conditioning, Animal ; }, abstract = {Gut microbes may be the critical mediators for the cognitive enhancing effects of exercise. Via fecal microbiota transplantation (FMT), this study is aimed at determining the mechanism of how voluntary exercise improved learning and memory ability impairment post a high-fat, high-cholesterol (HFHC) diet. The learning and memory abilities assessed via the Morris water maze in the FMT recipient group of voluntary exercising mice were improved compared to sedentary group. 16S rRNA gene sequencing results indicated that exercise-induced changes in gut microbiota distribution were transmissible, mainly in terms of elevated Lactobacillus, Lactobacillus, and Eubacterium nodatum, as well as decreased Clostrida_UCG-014 and Akkermansia after FMT. The neuroprotective effects of FMT were mainly related to the improved insulin signaling pathway (IRS2/PI3K/AKT) and mitochondrial function; inhibition of AQP4; decreased p-Tau at serine 396 and 404; increased BDNF, PSD95, and synaptophysin in the hippocampus; and also decreased HDAC2 and HDAC3 protein expressions in the nuclear and cytoplasmic fractions of the hippocampus. The findings of qRT-PCR suggested that exercise-induced gut microbes, on the one hand, elevated GPR109A and decreased GPR43 and TNF-α in the hippocampus. On the other hand, it increased GPR109A and GPR41 expressions in the proximal colon tissue. In addition, total short-chain fatty acid (SCFA), acetic acid, propionic acid, isobutyric acid, valeric acid, and isovaleric acid contents were also elevated in the cecum. In conclusion, exercise-induced alterations in gut microbiota play a decisive role in ameliorating HFHC diet-induced cognitive deficits. FMT treatment may be a new considerable direction in ameliorating cognitive impairment induced by exposure to HFHC diet.}, }
@article {pmid36712100, year = {2023}, author = {Natarajan, A and Fremin, BJ and Schmidtke, DT and Wolfe, MK and Zlitni, S and Graham, KE and Brooks, EF and Severyn, CJ and Sakamoto, KM and Lacayo, NJ and Kuersten, S and Koble, J and Caves, G and Kaplan, I and Singh, U and Jagannathan, P and Rezvani, AR and Bhatt, AS and Boehm, AB}, title = {Tomato brown rugose fruit virus Mo gene is a novel microbial source tracking marker.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36712100}, issn = {2692-8205}, support = {R01 AI143757/AI/NIAID NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; T32 DK098132/DK/NIDDK NIH HHS/United States ; T32 GM007276/GM/NIGMS NIH HHS/United States ; }, abstract = {UNLABELLED: Microbial source tracking (MST) identifies sources of fecal contamination in the environment using fecal host-associated markers. While there are numerous bacterial MST markers, there are few viral markers. Here we design and test novel viral MST markers based on tomato brown rugose fruit virus (ToBRFV) genomes. We assembled eight nearly complete genomes of ToBRFV from wastewater and stool samples from the San Francisco Bay Area in the United States of America. Next, we developed two novel probe-based RT-PCR assays based on conserved regions of the ToBRFV genome, and tested the markers’ sensitivities and specificities using human and non-human animal stool as well as wastewater. TheToBRFV markers are sensitive and specific; in human stool and wastewater, they are more prevalent and abundant than a currently used marker, the pepper mild mottle virus (PMMoV) coat protein (CP) gene. We applied the assays to detect fecal contamination in urban stormwater samples and found that the ToBRFV markers matched cross-assembly phage (crAssphage), an established viral MST marker, in prevalence across samples. Taken together, ToBRFV is a promising viral human-associated MST marker.<br><br>IMPORTANCE: Human exposure to fecal contamination in the environment can cause transmission of infectious diseases. Microbial source tracking (MST) can identify sources of fecal contamination so that contamination can be remediated and human exposures can be reduced. MST requires the use of fecal host-associated MST markers. Here we design and test novel MST markers from genomes of tomato brown rugose fruit virus (ToBRFV). The markers are sensitive and specific to human stool, and highly abundant in human stool and wastewater samples.}, }
@article {pmid36710337, year = {2023}, author = {Tian, F and Li, Y and Wang, Y and Yu, B and Song, J and Ning, Q and Jian, C and Ni, M}, title = {Risk factors and molecular epidemiology of fecal carriage of carbapenem resistant Enterobacteriaceae in patients with liver disease.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {22}, number = {1}, pages = {10}, pmid = {36710337}, issn = {1476-0711}, mesh = {Adult ; Humans ; *Carbapenem-Resistant Enterobacteriaceae ; Anti-Bacterial Agents/pharmacology/therapeutic use ; *Enterobacteriaceae Infections/epidemiology/drug therapy ; Carbapenems/pharmacology ; Molecular Epidemiology ; Multilocus Sequence Typing ; beta-Lactamases/genetics ; Escherichia coli ; Klebsiella pneumoniae ; Risk Factors ; *Liver Diseases ; Cephalosporins ; }, abstract = {BACKGROUND: Carbapenem resistant Enterobacteriaceae (CRE) colonization is a risk factor for CRE infection. CRE infection results in an increase in mortality in patients with cirrhosis. However, minimal data regarding the prevalence and the risk factors of CRE colonization in patients with liver disease yet without liver transplantation are available. The present study aimed to investigate the prevalence, risk factors and molecular epidemiology characteristics of CRE fecal carriage among patients with liver disease.<br><br>METHODS: Stool specimens from 574 adult inpatients with liver disease were collected from December 2020 to April 2021. CRE were screened using selective chromogenic agar medium and identified by the Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using the broth microdilution method. Carbapenemase genes were characterized by polymerase chain reaction (PCR) and DNA sequencing. Multilocus sequence typing (MLST) was performed for Carbapenem Resistant Klebsiella pneumoniae (CR-KPN) isolates and Carbapenem Resistant Escherichia Coli (CR-ECO) isolates.<br><br>RESULTS: The total number of stool specimens (732) were collected from 574 patients with liver disease. 43 non-duplicated CRE strains were isolated from 39 patients with a carriage rate of 6.79% (39/574). The carriage rate was 15.60% (17/109) in patients with acute-on-chronic liver failure (ACLF). Multivariate analysis indicated that ACLF (P&#x2009;=&#x2009;0.018), the history of pulmonary infection within past 3&#xa0;months (P&#x2009;=&#x2009;0.001) and the use of third generation cephalosporin/&#x3b2;-lactamases inhibitor within past 3&#xa0;months (P&#x2009;=&#x2009;0.000) were independent risk factors of CRE colonization in patients with liver disease. Klebsiella Pnuemoniae (KPN) (51.28%) and Escherichia coli (ECO) (30.77%) were main strains in these patients. All CRE strains showed high resistance to most antimicrobials except for polymyxin B and tigecycline. Most (83.72%, 36/43) of the CRE carried carbapenemase genes. blaKPC-2 was the major carbapenemase gene. The molecular epidemiology of KPN were dominated by ST11, while the STs of ECO were scattered.<br><br>CONCLUSIONS: The present study revealed that CRE fecal carriage rates were higher in patients with ACLF than in patients without liver failure. ACLF, the history of pulmonary infection within past 3&#xa0;months and the use of third generation cephalosporin/&#x3b2;-lactamases inhibitor within past 3&#xa0;months were independent risk factors of CRE colonization in patients with liver disease. Regular CRE screening for hospitalized patients with liver disease should be conducted to limit the spread of CRE strain.}, }
@article {pmid36710269, year = {2023}, author = {Zhao, Q and Yu, J and Zhou, H and Wang, X and Zhang, C and Hu, J and Hu, Y and Zheng, H and Zeng, F and Yue, C and Gu, L and Wang, Z and Zhao, F and Zhou, P and Zhang, H and Huang, N and Wu, W and Zhou, Y and Li, J}, title = {Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {40}, pmid = {36710269}, issn = {2059-3635}, mesh = {*Dysbiosis/complications ; Vascular Endothelial Growth Factor A/genetics ; Aminoquinolines/adverse effects ; Fatty Acids ; Inflammation/pathology ; Phenotype ; Mice, Transgenic ; Bacteroidetes ; Cytokines/genetics ; Animals ; Mice ; *Psoriasis/genetics ; }, abstract = {The intestinal microbiota has been associated with host immunity as well as psoriasis; however, the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically. Here, we sought to examine its role and mechanism of action in the pathogenesis of psoriasis. We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota. We performed co-housing and fecal microbial transplantation (FMT) experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms, including increasing the infiltration and differentiation of Th17, and increased the abundance of Prevotella, while decreasing that of Parabacteroides distasonis, in the colon. These alterations affected fatty acid metabolism, increasing the abundance of oleic and stearic acids. Meanwhile, gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod (IMQ)-induced psoriasis-like mice. Indeed, administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo, as well as increased the secretion of IL-23 by stimulating DCs in vitro. At last, we found that, treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota, including the decrease of Prevotella and increase of Parabacteroides distasonis. Overall, our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice, suggesting a new target for the clinical diagnosis and treatment of psoriasis.}, }
@article {pmid36706918, year = {2023}, author = {Lu, T and Li, Q and Lin, W and Zhao, X and Li, F and Ji, J and Zhang, Y and Xu, N}, title = {Gut Microbiota-Derived Glutamine Attenuates Liver Ischemia/Reperfusion Injury via Macrophage Metabolic Reprogramming.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {15}, number = {5}, pages = {1255-1275}, pmid = {36706918}, issn = {2352-345X}, mesh = {Mice ; Animals ; Glutamine/pharmacology/metabolism ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Mice, Inbred C57BL ; Liver/metabolism ; Macrophages/metabolism ; *Reperfusion Injury/metabolism ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Ischemia/metabolism ; }, abstract = {BACKGROUND &amp; AIMS: Many studies have revealed crucial roles of the gut microbiota and its metabolites in liver disease progression. However, the mechanism underlying their effects on liver ischemia/reperfusion (I/R) injury remain largely unknown. Here, we investigate the function of gut microbiota and its metabolites in liver I/R injury.<br><br>METHODS: C57BL/6 mice was pretreated with an antibiotic cocktail. Then, we used multi-omics detection methods including 16s rRNA sequencing, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) to explore the changes of gut microbiota and metabolites in both feces and portal blood to reveal the mechanism of their protective effect in liver I/R injury.<br><br>RESULTS: We found that antibiotic pretreatment (ABX) could significantly reduce the severity of I/R-induced hepatic injury, and this effect could be transferred to germ-free mice by fecal microbiota transplantation (FMT), suggesting a protective role of the gut microbiota depletion. During I/R, the rates of serum &#x3b1;-ketoglutarate (&#x3b1;KG) production and glutamate reduction, downstream products of gut microbiota-derived glutamine, were more significant in the ABX mice. Then, we showed that &#x3b1;KG could promote alternative (M2) macrophage activation through oxidative phosphorylation, and oligomycin A could inhibit M2 macrophage polarization and reversed this protective effect.<br><br>CONCLUSIONS: These findings show that the gut microbiota and its metabolites play critical roles in hepatic I/R injury by modulating macrophage metabolic reprogramming. Potential therapies that target macrophage metabolism, including antibiotic therapies and novel immunometabolism modulators, can be exploited for the treatment of liver I/R injury.}, }
@article {pmid36704100, year = {2022}, author = {Wu, Z and Zhang, B and Chen, F and Xia, R and Zhu, D and Chen, B and Lin, A and Zheng, C and Hou, D and Li, X and Zhang, S and Chen, Y and Hou, K}, title = {Fecal microbiota transplantation reverses insulin resistance in type 2 diabetes: A randomized, controlled, prospective study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1089991}, pmid = {36704100}, issn = {2235-2988}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Diabetes Mellitus, Type 2/therapy ; *Insulin Resistance ; Prospective Studies ; Blood Glucose/metabolism ; *Metformin/therapeutic use ; Feces/microbiology ; }, abstract = {OBJECTIVES: Recent studies have shown that fecal microbiota transplantation (FMT) improved the metabolic profiles of patients with type 2 diabetes mellitus (T2DM), yet the effectiveness in reversing insulin resistance and increasing metformin sensitivity in T2DM patients have not been reported. In this study, we evaluated the improvements of T2DM patients and their gut microbiota by FMT alone and FMT plus metformin.<br><br>METHODS: A total of 31 patients with newly diagnosed T2DM were randomized to intervention by metformin, FMT, or FMT plus metformin in the study. Patients were followed up at baseline and week 4 after treatment. Blood and stool samples were collected and subject to analyze clinical parameters and microbial communities by metagenomic sequencing, respectively.<br><br>RESULTS: FMT alone and FMT plus metformin significantly improved the clinical indicators HOMA-IR and BMI in T2DM, besides fasting blood glucose, postprandial blood glucose, and hemoglobin A1c that were also controlled by metformin. Donor microbiota effectively colonized in T2DM with slightly higher colonization ration in FMT than FMT plus metformin within 4 weeks, resulting in increased microbial diversity and community changes from baseline after treatment. A total of 227 species and 441 species were significantly alerted after FMT and FMT plus metformin, respectively. FMT were significantly associated with the clinical parameters. Among them, Chlorobium phaeovibrioides, Bifidibacterium adolescentis and Synechococcus sp.WH8103 were potential due to their significantly negative correlations with HOMA-IR.<br><br>CONCLUSIONS: FMT with or without metformin significantly improve insulin resistance and body mass index and gut microbial communities of T2DM patients by colonization of donor-derived microbiota.}, }
@article {pmid36701104, year = {2023}, author = {Fan, L and Zeng, X and Xu, G}, title = {Metformin Regulates Gut Microbiota Abundance to Suppress M2 Skewing of Macrophages and Colorectal Tumorigenesis in Mice.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {61}, number = {1}, pages = {109-120}, pmid = {36701104}, issn = {1976-3794}, mesh = {Humans ; Mice ; Animals ; *Colorectal Neoplasms/metabolism ; *Gastrointestinal Microbiome ; Carcinogenesis/metabolism ; *Microbiota ; Bacteroidetes ; Macrophages/metabolism ; Mice, Inbred C57BL ; }, abstract = {The correlation of imbalanced gut microbiota with the onset and progression of colorectal cancer (CRC) has become clear. This work investigates the effect of metformin on gut microbiota and genesis of CRC in mice. Human fecal samples were collected from healthy control (HC) donors and CRC patients. Compared to HC donors, CRC patients had reduced abundance of gut microbiota; however, they had increased abundance of detrimental Bacteroidetes. Mice were injected with azomethane (AOM) to induce colorectal tumorigenesis models. Treatment of CRC patients-sourced fecal microbiota promoted tumorigenesis, and it increased the expression of Ki67, β-catenin, COX-2, and Cyclin D1 in mouse colon tissues. Further treatment of metformin blocked the colorectal tumorigenesis in mice. Fecal microbiota from the metformin-treated mice was collected, which showed decreased Bacteroidetes abundance and suppressed AOM-induced colorectal tumorigenesis in mice as well. Moreover, the metformin- modified microbiota promoted the M1 macrophage-related markers IL-6 and iNOS but suppressed the M2 macrophage-related markers IL-4R and Arg1 in mouse colon tissues. In conclusion, this study suggests that metformin-mediated gut microbiota alteration suppresses macrophage M2 polarization to block colorectal tumorigenesis.}, }
@article {pmid36700221, year = {2022}, author = {Chen, L and Ruan, G and Cheng, Y and Yi, A and Chen, D and Wei, Y}, title = {The role of Th17 cells in inflammatory bowel disease and the research progress.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1055914}, pmid = {36700221}, issn = {1664-3224}, mesh = {Humans ; *Th17 Cells ; *Inflammatory Bowel Diseases ; Intestinal Mucosa ; Cytokines ; Inflammation ; }, abstract = {Th17 cells play an important role in the abnormal immune response in inflammatory bowel disease (IBD) and are involved in the development and progression of inflammation and fibrosis. An increasing amount of data has shown that gut microbes are important parts of intestinal immunity and regulators of Th17 cellular immunity. Th17 cell differentiation is regulated by intestinal bacteria and cytokines, and Th17 cells regulate the intestinal mucosal immune microenvironment by secreting cytokines, such as IL-17, IL-21, and IL-26. Solid evidence showed that, regarding the treatment of IBD by targeting Th17 cells, the therapeutic effect of different biological agents varies greatly. Fecal bacteria transplantation (FMT) in the treatment of IBD has been a popular research topic in recent years and is safe and effective with few side effects. To further understand the role of Th17 cells in the progression of IBD and associated therapeutic prospects, this review will discuss the progress of related research on Th17 cells in IBD by focusing on the interaction and immune regulation between Th17 cells and gut microbiota.}, }
@article {pmid36698844, year = {2022}, author = {Chopra, T and Hecht, G and Tillotson, G}, title = {Gut microbiota and microbiota-based therapies for Clostridioides difficile infection.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1093329}, pmid = {36698844}, issn = {2296-858X}, abstract = {Clostridioides difficile infection poses significant clinical challenges due to its recurrent nature. Current antibiotic management does not address the underlying issue, that of a disturbed gastrointestinal microbiome, called dysbiosis. This provides a supportive environment for the germination of C. difficile spores which lead to infection and toxin production as well as an array of other health conditions. The use of microbiome restoration therapies such as live biotherapeutics can reverse dysbiosis and lead to good clinical outcomes. Several such therapies are under clinical investigation.}, }
@article {pmid36693853, year = {2023}, author = {Chadchan, SB and Naik, SK and Popli, P and Talwar, C and Putluri, S and Ambati, CR and Lint, MA and Kau, AL and Stallings, CL and Kommagani, R}, title = {Gut microbiota and microbiota-derived metabolites promotes endometriosis.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {28}, pmid = {36693853}, issn = {2058-7716}, support = {R01 CA220297/CA/NCI NIH HHS/United States ; R00 HD080742/HD/NICHD NIH HHS/United States ; R01 CA216426/CA/NCI NIH HHS/United States ; R01 HD065435/HD/NICHD NIH HHS/United States ; R01 HD102680/HD/NICHD NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; }, abstract = {Endometriosis is a pathological condition of the female reproductive tract characterized by the existence of endometrium-like tissue at ectopic sites, affecting 10% of women between the age 15 and 49 in the USA. However, currently there is no reliable non-invasive method to detect the presence of endometriosis without surgery and many women find hormonal therapy and surgery as ineffective in avoiding the recurrences. There is a lack of knowledge on the etiology and the factors that contribute to the development of endometriosis. A growing body of recent evidence suggests an association between gut microbiota and endometriosis pathophysiology. However, the direct impact of microbiota and microbiota-derived metabolites on the endometriosis disease progression is largely unknown. To understand the causal role of gut microbiota and endometriosis, we have implemented a novel model using antibiotic-induced microbiota-depleted (MD) mice to investigate the endometriosis disease progression. Interestingly, we found that MD mice showed reduced endometriotic lesion growth and, the transplantation of gut microbiota by oral gavage of feces from mice with endometriosis rescued the endometriotic lesion growth. Additionally, using germ-free donor mice, we indicated that the uterine microbiota is dispensable for endometriotic lesion growth in mice. Furthermore, we showed that gut microbiota modulates immune cell populations in the peritoneum of lesions-bearing mice. Finally, we found a novel signature of microbiota-derived metabolites that were significantly altered in feces of mice with endometriosis. Finally, we found one the altered metabolite, quinic acid promoted the survival of endometriotic epithelial cells in vitro and lesion growth in vivo, suggesting the disease-promoting potential of microbiota-derived metabolites. In summary, these data suggest that gut microbiota and microbiota-derived metabolome contribute to lesion growth in mice, possibly through immune cell adaptations. Of translational significance, these findings will aid in designing non-invasive diagnostics using stool metabolites for endometriosis.}, }
@article {pmid36693599, year = {2023}, author = {Hou, Q and Huang, J and Zhao, L and Pan, X and Liao, C and Jiang, Q and Lei, J and Guo, F and Cui, J and Guo, Y and Zhang, B}, title = {Dietary genistein increases microbiota-derived short chain fatty acid levels, modulates homeostasis of the aging gut, and extends healthspan and lifespan.}, journal = {Pharmacological research}, volume = {188}, number = {}, pages = {106676}, doi = {10.1016/j.phrs.2023.106676}, pmid = {36693599}, issn = {1096-1186}, mesh = {Mice ; Animals ; Longevity ; Genistein/pharmacology ; *Frailty ; Fatty Acids, Volatile/pharmacology ; Aging ; Inflammation ; *Gastrointestinal Microbiome ; Homeostasis ; Mice, Inbred C57BL ; Mammals ; }, abstract = {Age-related gastrointestinal decline contributes to whole-organism frailty and mortality. Genistein is known to have beneficial effects on age-related diseases, but its precise role in homeostasis of the aging gut remains to be elucidated. Here, wild-type aging mice and Zmpste24[-/-] progeroid mice were used to investigate the role of genistein in lifespan and homeostasis of the aging gut in mammals. A series of longitudinal, clinically relevant measurements were performed to evaluate the effect of genistein on healthspan. It was found that dietary genistein promoted a healthier and longer life and was associated with a decrease in the levels of systemic inflammatory cytokines in aging mice. Furthermore, dietary genistein ameliorated gut dysfunctions, such as intestinal inflammation, leaky gut, and impaired epithelial regeneration. A distinct genistein-mediated alteration in gut microbiota was observed by increasing Lachnospira abundance and short-chain fatty acid (SCFA) production. Further fecal microbiota transplantation and dirty cage sharing experiments indicated that the gut microbiota from genistein-fed mice rejuvenated the aging gut and extended the lifespan of progeroid mice. It was demonstrated that genistein-associated SCFAs alleviated tumor necrosis factor alpha-induced intestinal organoid damage. Moreover, genistein-associated propionate promoted regulatory T cell-derived interleukin 10 production, which alleviated macrophage-derived inflammation. This study provided the first data, to the authors' knowledge, indicating that dietary genistein modulates homeostasis in the aging gut and extends the healthspan and lifespan of aging mammals. Moreover, the existence of a link between genistein and the gut microbiota provides a rationale for dietary interventions against age-associated frailty.}, }
@article {pmid36692308, year = {2023}, author = {Pensinger, DA and Fisher, AT and Dobrila, HA and Van Treuren, W and Gardner, JO and Higginbottom, SK and Carter, MM and Schumann, B and Bertozzi, CR and Anikst, V and Martin, C and Robilotti, EV and Chow, JM and Buck, RH and Tompkins, LS and Sonnenburg, JL and Hryckowian, AJ}, title = {Butyrate Differentiates Permissiveness to Clostridioides difficile Infection and Influences Growth of Diverse C. difficile Isolates.}, journal = {Infection and immunity}, volume = {91}, number = {2}, pages = {e0057022}, pmid = {36692308}, issn = {1098-5522}, support = {R01 CA200423/CA/NCI NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Humans ; Animals ; Mice ; *Clostridioides difficile ; Butyrates ; Permissiveness ; *Clostridium Infections ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Fatty Acids, Volatile ; }, abstract = {A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota-accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C. difficile and for developing alternative approaches for coping with this pathogen. One prominent class of metabolites produced by the gut microbiome is short-chain fatty acids (SCFAs), the major metabolic end products of MAC metabolism. SCFAs are known to decrease the fitness of C. difficile in vitro, and high intestinal SCFA concentrations are associated with reduced fitness of C. difficile in animal models of C. difficile infection (CDI). Here, we use controlled dietary conditions (8 diets that differ only by MAC composition) to show that C. difficile fitness is most consistently impacted by butyrate, rather than the other two prominent SCFAs (acetate and propionate), during murine model CDI. We similarly show that butyrate concentrations are lower in fecal samples from humans with CDI than in those from healthy controls. Finally, we demonstrate that butyrate impacts growth in diverse C. difficile isolates. These findings provide a foundation for future work which will dissect how butyrate directly impacts C. difficile fitness and will lead to the development of diverse approaches distinct from antibiotics or fecal transplant, such as dietary interventions, for mitigating CDI in at-risk human populations. IMPORTANCE Clostridioides difficile is a leading cause of infectious diarrhea in humans, and it imposes a tremendous burden on the health care system. Current treatments for C. difficile infection (CDI) include antibiotics and fecal microbiota transplant, which contribute to recurrent CDIs and face major regulatory hurdles, respectively. Therefore, there is an ongoing need to develop new ways to cope with CDI. Notably, a disrupted "dysbiotic" gut microbiota is the primary risk factor for CDI, but we incompletely understand how a healthy microbiota resists CDI. Here, we show that a specific molecule produced by the gut microbiota, butyrate, is negatively associated with C. difficile burdens in humans and in a mouse model of CDI and that butyrate impedes the growth of diverse C. difficile strains in pure culture. These findings help to build a foundation for designing alternative, possibly diet-based, strategies for mitigating CDI in humans.}, }
@article {pmid36689162, year = {2023}, author = {Lin, MC and Peng, ZY and Chou, HC and Tsai, YT and Wei, YS and Wang, YS and Wang, YL and Chang, SJ and Chan, HL}, title = {Fecal Protein Analysis of Dusp6 Knockout C57BL/6J Mice by Metaproteomics.}, journal = {Applied biochemistry and biotechnology}, volume = {195}, number = {7}, pages = {4215-4236}, pmid = {36689162}, issn = {1559-0291}, mesh = {Mice ; Animals ; Mice, Knockout ; Mice, Inbred C57BL ; *Obesity/genetics ; Diet ; *Microbiota ; }, abstract = {The research of obesity and gut microbiota has been carried out for years, yet the study process was in a slow pace for several challenges to conquer. As a complex status of disorder, the contributing factors refer to gut microbiota about obesity were controversial in a wide range. In terms of proteomics, 2D-DIGE technology is a powerful method for this study to identify fecal proteins from lean microbiota in Dusp6 knockout C57BL/6J mice, exploring the protein markers of the ability resisting to diet-induced obesity (DIO) transferred to the host mice after fecal microbiota transplantation. The results showed that the fecal microbiota expressed 289 proteins differentially with 23 proteins identified, which were considered to be the reasons to assist the microbiota exhibiting distinct behavior. By means of proteomics technology, we had found that differentially expressed proteins of lean microbiota determined the lean microbial behavior might be able to resist leaky gut. To sum up our study, the proteomics strategies offered as a tool to demonstrate and analyze the features of lean microbiota, providing new speculations in the behavior about the gut microbiota reacting to DIO.}, }
@article {pmid36689003, year = {2023}, author = {Rajindrajith, S and Devanarayana, NM and Thapar, N and Benninga, MA}, title = {Myths and misconceptions about childhood constipation.}, journal = {European journal of pediatrics}, volume = {182}, number = {4}, pages = {1447-1458}, pmid = {36689003}, issn = {1432-1076}, mesh = {Child ; Humans ; *Quality of Life ; *Constipation/diagnosis/etiology/therapy ; Laxatives/therapeutic use ; Colon ; Diet ; }, abstract = {Many widely held beliefs and assumptions concerning childhood constipation continue to interfere with rational management of childhood constipation. Although many still believe that constipation is not a common disease, about 9.5% of the world's children suffer from chronic constipation. Most of these children live in non-Western countries. There are major misconceptions about the etiology of constipation as a significant proportion of clinicians still believe that constipation is caused by some form an organic pathology, whereas in reality, the majority have functional constipation. Contrary to a commonly held belief that children outgrow constipation without long-term problems, there is evidence that constipation leads to significant bowel and psychological consequences and has a major impact on the quality of life which detrimentally affects future health and education. Finally, ineffective management strategies such as increasing fiber and water in the diet, and short duration of treatment owing to the fear that long-term laxative treatment leads to colonic dysfunction, interfere with effective therapeutic strategies. Conclusions: It is apparent that myths and misconception often lead to wrong assumptions regarding the distribution of the disease, its etiology, pathophysiology, and management leading to ordering incorrect investigations and ineffective therapeutic strategies while spending large sums of public funds unnecessarily. Poorly treated constipation leads to deleterious psychological consequences predisposing children to develop significant psychological damage and bowel dysfunctions. This review aims to challenge these myths about various elements of constipation by exploring the existing literature and encouraging clinicians to have a fresh look at old concepts that could interfere with the well-being of children with constipation. What is Known: • Childhood constipation is a growing problem in the world leading to significant suffering and high healthcare expenditure • Myths and misconceptions lead to poor management strategies causing psychological and bowel damage What is New: • Organic, systemic, and bowel disorders leading to constipation are uncommon, and in the majority, it arises due to deliberate fecal withholding and most investigations ordered by clinicians are not very helpful in the management • Most non-pharmacological interventions are not effective in the day-to-day management of childhood constipation. The use of laxatives is considered to be the first-line management strategy.}, }
@article {pmid36688695, year = {2023}, author = {Pan, J and Chui, L and Liu, T and Zheng, Q and Liu, X and Liu, L and Zhao, Y and Zhang, L and Song, M and Han, J and Huang, J and Tang, C and Tao, C and Zhao, J and Wang, Y}, title = {Fecal Microbiota Was Reshaped in UCP1 Knock-In Pigs via the Adipose-Liver-Gut Axis and Contributed to Less Fat Deposition.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0354022}, pmid = {36688695}, issn = {2165-0497}, mesh = {Humans ; Animals ; Swine ; Mice ; Uncoupling Protein 1/genetics/metabolism ; *Obesity/metabolism ; Liver/metabolism ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; }, abstract = {The relationship between the host gut microbiota and obesity has been well documented in humans and mice; however, few studies reported the association between the gut microbiota and fat deposition in pigs. In a previous study, we generated uncoupling protein 1 (UCP1) knock-in pigs (UCP1 pigs), which exhibited a lower fat deposition phenotype. Whether the gut microbiota was reshaped in these pigs and whether the reshaped gut microbiota contributes to the lower fat content remain unknown. Here, we revealed that the fecal microbiota composition and metabolites were significantly altered under both chow diet (CD) and high-fat/high-cholesterol (HFHC) diet conditions in UCP1 pigs compared to those in wild-type (WT) pigs. The abundance of Oscillospira and Coprococcus and the level of metabolite hyodeoxycholic acid (HDCA) from feces were observed to be significantly increased in UCP1 pigs. An association analysis revealed that Oscillospira and Coprococcus were significantly negatively related to backfat thickness. In addition, after fecal microbiota transplantation (FMT), the mice that were orally gavaged with feces from UCP1 pigs exhibited less fat deposition under both CD and high-fat diet (HFD) conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Consistently, HDCA-treated mice also exhibited reduced fat content. Mechanistically, we found that UCP1 expression in white adipose tissue alters the gut microbiota via the adipose-liver-gut axis in pigs. Our study provides new data concerning the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolites in the regulation of fat deposition in pigs. IMPORTANCE This article investigated the effect of the ectopic expression of UCP1 on the regulation of fecal microbiota composition and metabolites and which alters the fat deposition phenotype. Bacteria, including Oscillospira and Coprococcus, and the metabolite HDCA were found to be significantly increased in feces of UCP1 pigs and had a negative relationship with backfat thickness. Mice with fecal microbiota transplantation phenocopied the UCP1 pigs under both CD and HFD conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Our study provides new data regarding the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolic production in the regulation of fat deposition in pigs.}, }
@article {pmid36688692, year = {2023}, author = {Strahm, N and Didriksen, H and Fretheim, H and Molberg, &#xd8; and Midtvedt, &#xd8; and Farstad, IN and Midtvedt, T and Lundin, KEA and Aabakken, L and Błyszczuk, P and Distler, O and Kania, G and Hoffmann-Vold, AM}, title = {Effects of faecal microbiota transplantation on the small intestinal mucosa in systemic sclerosis.}, journal = {Rheumatology (Oxford, England)}, volume = {62}, number = {8}, pages = {2918-2929}, pmid = {36688692}, issn = {1462-0332}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; Double-Blind Method ; Intestines ; Intestinal Mucosa ; *Scleroderma, Systemic/therapy/etiology ; Treatment Outcome ; }, abstract = {OBJECTIVES: In SSc, gastrointestinal tract (GIT) involvement is a major concern, with no disease-modifying and limited symptomatic therapies available. Faecal microbiota transplantation (FMT) represents a new therapeutic option for GIT-affliction in SSc, showing clinical promise in a recent controlled pilot trial. Here, we aim to investigate effects of FMT on duodenal biopsies collected from SSc patients by immunohistochemistry and transcriptome profiling.<br><br>METHODS: We analysed duodenal biopsies obtained pre-intervention (week 0) and post-intervention (weeks 2 and 16) from nine SSc patients receiving an intestinal infusion of FMT (n&#x2009;=&#x2009;5) or placebo (n&#x2009;=&#x2009;4). The analysis included immunohistochemistry (IHC) with a selected immune function and fibrosis markers, and whole biopsy transcriptome profiling.<br><br>RESULTS: In patients receiving FMT, the number of podoplanin- and CD64-expressing cells in the mucosa were lower at week 2 compared with baseline. This decline in podoplanin- (r&#x2009;=&#x2009;0.94) and CD64-positive (r&#x2009;=&#x2009;0.89) cells correlated with improved patient-reported lower GIT symptoms. Whole biopsy transcriptome profiling from week 2 showed significant enrichment of pathways critical for cellular and endoplasmic reticulum stress responses, microvillus and secretory vesicles, vascular and sodium-dependent transport, and circadian rhythm. At week 16, we found enrichment of pathways mandatory for binding activity of immunoglobulin receptors, T cell receptor complexes, and chemokine receptors, as well as response to zinc-ions. We found that 25 genes, including Matrix metalloproteinase-1 were upregulated at both week 2 and week 16.<br><br>CONCLUSION: Combining selective IHC and unbiased gene expression analyses, this exploratory study highlights the potential for disease-relevant organ effects of FMT in SSc patients with GIT involvement.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03444220.}, }
@article {pmid36687192, year = {2023}, author = {Aydin, OC and Aydın, S and Barun, S}, title = {Role of natural products and intestinal flora on type 2 diabetes mellitus treatment.}, journal = {World journal of clinical cases}, volume = {11}, number = {1}, pages = {65-72}, pmid = {36687192}, issn = {2307-8960}, abstract = {Diabetes mellitus (DM) is a complicated, globally expanding disease that is influenced by hereditary and environmental variables. Changes in modern society's food choices, physical inactivity, and obesity are significant factors in the development of type 2 DM (T2DM). The association between changes in intestinal flora and numerous disorders, including obesity, diabetes, and cardiovascular diseases, has been studied in recent years. The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients' intestinal flora, as well as their therapeutic choices. Also included is a summary of the anti-diabetic benefits of natural compounds demonstrated by studies. The short-chain fatty acids theory, the bile acid theory, and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM. Due to an intestinal flora imbalance, abnormalities in short-chain fatty acids and secondary bile acids have been found in diabetic patients. Additionally, metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation. The agenda for diabetes treatment includes the use of short-chain fatty acids, probiotics, prebiotics in the diet, fecal bacteria transplantation, and antibiotics. Animal studies have proven the antidiabetic benefits of numerous bioactive substances, including Flavonoids, Alkaloids, Saponin, and Allicin. However, further research is required to contribute to the treatment of diabetes.}, }
@article {pmid36687179, year = {2023}, author = {Yan, XX and Wu, D}, title = {Intestinal microecology-based treatment for inflammatory bowel disease: Progress and prospects.}, journal = {World journal of clinical cases}, volume = {11}, number = {1}, pages = {47-56}, pmid = {36687179}, issn = {2307-8960}, abstract = {Inflammatory bowel disease (IBD) is a chronic, recurrent, and debilitating disorder, and includes Crohn's disease and ulcerative colitis. The pathogenesis of IBD is closely associated with intestinal dysbiosis, but has not yet been fully clarified. Genetic and environmental factors can influence IBD patients' gut microbiota and metabolism, disrupt intestinal barriers, and trigger abnormal immune responses. Studies have reported the alteration of gut microbiota and metabolites in IBD, providing the basis for potential therapeutic options. Intestinal microbiota-based treatments such as pre/probiotics, metabolite supplementation, and fecal microbiota transplantation have been extensively studied, but their clinical efficacy remains controversial. Repairing the intestinal barrier and promoting mucosal healing have also been proposed. We here review the current clinical trials on intestinal microecology and discuss the prospect of research and practice in this field.}, }
@article {pmid36686492, year = {2022}, author = {Wang, G and Wang, Y and Bai, J and Li, G and Liu, Y and Deng, S and Zhou, R and Tao, K and Xia, Z}, title = {Increased plasma genistein after bariatric surgery could promote remission of NAFLD in patients with obesity.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {1024769}, pmid = {36686492}, issn = {1664-2392}, mesh = {Mice ; Animals ; *Non-alcoholic Fatty Liver Disease/complications ; Genistein ; Obesity/surgery/complications ; *Bariatric Surgery ; }, abstract = {BACKGROUND: Bariatric surgery is associated with a positive effect on the progress of non-alcoholic associated fatty liver disease (NAFLD). Although weight loss is the obvious mechanism, there are also weight-independent mechanisms.<br><br>METHODS: We collected blood samples from 5 patients with obesity before and 3 months after surgery and performed an LC-MS-based untargeted metabolomics test to detect potential systemic changes. We also constructed sleeve gastrectomy (SG) mice models. The plasma, liver and intestine samples were collected and analyzed by qPCR, ELISA and HPLC. Cohousing experiments and feces transplantation experiments were performed on mice to study the effect of gut microbiota. Genistein administration experiments were used to study the in vivo function of the metabolites.<br><br>RESULTS: Plasma genistein (GE) was identified to be elevated after surgery. Both clinical data and rodent models suggested that plasma GE is negatively related to the degree of NAFLD. We fed diet-induced obese (DIO) mice with GE, and we found that there was significant remission of NAFLD. Both in vivo and in vitro experiments showed that GE could restrict the inflammation state in the liver and thus relieve NAFLD. Finally, we used co-housing experiments to alter the gut microbiota in mice, and it was identified that sleeve gastrectomy (SG) mice had a special gut microbiota phenotype, which could result in higher plasma GE levels. By feces transplantation experiment (FMT), we found that only feces from the SG mice (and not from other lean mice) could induce higher plasma GE levels.<br><br>CONCLUSION: Our studies showed that SG but not calorie restriction could induce higher plasma GE levels by altering the gut microbiota. This change could promote NAFLD remission. Our study provides new insights into the systemic effects of bariatric surgery. Bariatric surgery could affect remote organs via altered metabolites from the gut microbiota. Our study also identified that additional supplement of GE after surgery could be a therapy for NAFLD.}, }
@article {pmid36685764, year = {2022}, author = {Minuti, A and Brufani, F and Menculini, G and Moretti, P and Tortorella, A}, title = {The complex relationship between gut microbiota dysregulation and mood disorders: A narrative review.}, journal = {Current research in neurobiology}, volume = {3}, number = {}, pages = {100044}, pmid = {36685764}, issn = {2665-945X}, abstract = {Gut microbiota regulates neurotransmission, neurogenesis, neuroinflammation, and neuroendocrine signaling. The aim of the present review is to analyze the literature concerning gut microbiota dysregulation and mood symptoms, with the specific hypothesis that such alterations play a role in the onset of mood disorders. Here, in fact, we review recent research focusing on how gut microbiota dysregulation influences the onset of mood disorders and on possible pathophysiological mechanisms involved in this interaction. We pay specific attention to the relationship between gut microbiota dysregulation and inflammatory state, Th17 differentiation, neuroactive factors, and TRP metabolism. The association between gut microbiota dysregulation and mood disorders is critically analyzed under a clinical point of view, also focusing on the emergence of mood symptoms in the context of medical conditions. These latter correlations may enable an interdisciplinary perspective in the clinical approach to such symptoms, as well as new treatment strategies, such as nutritional interventions, psychobiotics, antibiotics, as well as fecal microbiota transplantation.}, }
@article {pmid36683718, year = {2023}, author = {Senchukova, MA}, title = {Microbiota of the gastrointestinal tract: Friend or foe?.}, journal = {World journal of gastroenterology}, volume = {29}, number = {1}, pages = {19-42}, pmid = {36683718}, issn = {2219-2840}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Diseases/microbiology ; Inflammation/microbiology ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; *Probiotics ; }, abstract = {The gut microbiota is currently considered an external organ of the human body that provides important mechanisms of metabolic regulation and protection. The gut microbiota encodes over 3 million genes, which is approximately 150 times more than the total number of genes present in the human genome. Changes in the qualitative and quantitative composition of the microbiome lead to disruption in the synthesis of key bacterial metabolites, changes in intestinal barrier function, and inflammation and can cause the development of a wide variety of diseases, such as diabetes, obesity, gastrointestinal disorders, cardiovascular issues, neurological disorders and oncological concerns. In this review, I consider issues related to the role of the microbiome in the regulation of intestinal barrier function, its influence on physiological and pathological processes occurring in the body, and potential new therapeutic strategies aimed at restoring the gut microbiome. Herewith, it is important to understand that the gut microbiota and human body should be considered as a single biological system, where change of one element will inevitably affect its other components. Thus, the study of the impact of the intestinal microbiota on health should be considered only taking into account numerous factors, the role of which has not yet been fully elucidated.}, }
@article {pmid36683714, year = {2023}, author = {Luo, M and Xin, RJ and Hu, FR and Yao, L and Hu, SJ and Bai, FH}, title = {Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis.}, journal = {World journal of gastroenterology}, volume = {29}, number = {1}, pages = {144-156}, pmid = {36683714}, issn = {2219-2840}, mesh = {Animals ; *Hepatic Encephalopathy/etiology/therapy ; *Gastrointestinal Microbiome ; Dysbiosis/complications ; Liver Cirrhosis/complications ; *Probiotics/therapeutic use ; Brain ; }, abstract = {Minimal hepatic encephalopathy (MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety; however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.}, }
@article {pmid36683707, year = {2022}, author = {Chen, Q and Fan, Y and Zhang, B and Yan, C and Chen, Z and Wang, L and Hu, Y and Huang, Q and Su, J and Ren, J and Xu, H}, title = {Specific fungi associated with response to capsulized fecal microbiota transplantation in patients with active ulcerative colitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1086885}, pmid = {36683707}, issn = {2235-2988}, mesh = {Humans ; *Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Fungi/genetics ; Remission Induction ; Treatment Outcome ; }, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) is a novel microbial treatment for patients with ulcerative colitis (UC). In this study, we performed a clinical trial of capsulized FMT in UC patients to determine the association between the gut fungal community and capsulized FMT outcomes.<br><br>DESIGN: This study recruited patients with active UC (N = 22) and healthy individuals (donor, N = 9) according to the criteria. The patients received capsulized FMT three times a week. Patient stool samples were collected before (week 0) and after FMT follow-up visits at weeks 1, 4, and 12. Fungal communities were analysed using shotgun metagenomic sequencing.<br><br>RESULTS: According to metagenomic analysis, fungal community evenness index was greater in samples collected from patients, and the overall fungal community was clustered among the samples collected from donors. The dominant fungi in fecal samples collected from donors and patients were Ascomycota and Basidiomycota. However, capsulized FMT ameliorated microbial fungal diversity and altered fungal composition, based on metagenomic analysis of fecal samples collected before and during follow-up visits after capsulized FMT. Fungal diversity decreased in samples collected from patients who achieved remission after capsulized FMT, similar to samples collected from donors. Patients achieving remission after capsulized FMT had specific enrichment of Kazachstania naganishii, Pyricularia grisea, Lachancea thermotolerans, and Schizosaccharomyces pombe compared with patients who did not achieve remission. In addition, the relative abundance of P. grisea was higher in remission fecal samples during the follow-up visit. Meanwhile, decreased levels of pathobionts, such as Candida and Debaryomyces hansenii, were associated with remission in patients receiving capsulized FMT.<br><br>CONCLUSION: In the metagenomic analysis of fecal samples from donors and patients with UC receiving capsulized FMT, shifts in gut fungal diversity and composition were associated with capsulized FMT and validated in patients with active UC. We also identified the specific fungi associated with the induction of remission. ClinicalTrails.gov (NCT03426683).}, }
@article {pmid36683147, year = {2023}, author = {Jin, J and Xu, Z and Zhang, L and Zhang, C and Zhao, X and Mao, Y and Zhang, H and Liang, X and Wu, J and Yang, Y and Zhang, J}, title = {Gut-derived β-amyloid: Likely a centerpiece of the gut-brain axis contributing to Alzheimer's pathogenesis.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2167172}, pmid = {36683147}, issn = {1949-0984}, mesh = {Mice ; Humans ; Animals ; Aged ; Amyloid beta-Peptides/metabolism ; *Alzheimer Disease ; Amyloid Precursor Protein Secretases ; Brain-Gut Axis ; RNA, Ribosomal, 16S ; Mice, Transgenic ; *Gastrointestinal Microbiome/physiology ; Aspartic Acid Endopeptidases ; Amyloid beta-Protein Precursor/genetics/metabolism ; Disease Models, Animal ; }, abstract = {Peripheral β-amyloid (Aβ), including those contained in the gut, may contribute to the formation of Aβ plaques in the brain, and gut microbiota appears to exert an impact on Alzheimer's disease (AD) via the gut-brain axis, although detailed mechanisms are not clearly defined. The current study focused on uncovering the potential interactions among gut-derived Aβ in aging, gut microbiota, and AD pathogenesis. To achieve this goal, the expression levels of Aβ and several key proteins involved in Aβ metabolism were initially assessed in mouse gut, with key results confirmed in human tissue. The results demonstrated that a high level of Aβ was detected throughout the gut in both mice and human, and gut Aβ42 increased with age in wild type and mutant amyloid precursor protein/presenilin 1 (APP/PS1) mice. Next, the gut microbiome of mice was characterized by 16S rRNA sequencing, and we found the gut microbiome altered significantly in aged APP/PS1 mice and fecal microbiota transplantation (FMT) of aged APP/PS1 mice increased gut BACE1 and Aβ42 levels. Intra-intestinal injection of isotope or fluorescence labeled Aβ combined with vagotomy was also performed to investigate the transmission of Aβ from gut to brain. The data showed that, in aged mice, the gut Aβ42 was transported to the brain mainly via blood rather than the vagal nerve. Furthermore, FMT of APP/PS1 mice induced neuroinflammation, a phenotype that mimics early AD pathology. Taken together, this study suggests that the gut is likely a critical source of Aβ in the brain, and gut microbiota can further upregulate gut Aβ production, thereby potentially contributing to AD pathogenesis.}, }
@article {pmid36682132, year = {2023}, author = {Cao, S and Guo, D and Yin, H and Ding, X and Bai, S and Zeng, Q and Liu, J and Zhang, K and Mao, X and Wang, J}, title = {Improvement in ovarian function following fecal microbiota transplantation from high-laying rate breeders.}, journal = {Poultry science}, volume = {102}, number = {3}, pages = {102467}, pmid = {36682132}, issn = {1525-3171}, mesh = {Animals ; Female ; Chickens/physiology ; Cytokines ; Dietary Supplements ; *Fecal Microbiota Transplantation/veterinary ; Follicle Stimulating Hormone ; RNA, Messenger ; Sirtuin 1 ; }, abstract = {The underlying mechanism between the gut microbiota and reproductive function is not yet well-known. This study was conducted to investigate the effect of the administration of fecal microbiota transplantation (FMT) from highly laying rate donors on the cecal microbiota, intestinal health and ovarian function in broiler breeders. A total of 60 broiler breeders (53 wk of age) were selected by their laying rate [high (HP, 90.67 ± 0.69%; n = 10) and low (LP, 70.23 ± 0.87%; n = 20)]. The LP breeders were then be transplanted with fecal microbiota from HP hens (FMTHP; n = 10) or the same dosage of PBS (FMTCON; n = 10) for 28 d. The results revealed that FMT from HP donors increased egg-laying rate and serum hormone levels [17β-estradiol (E2), anti-Müller hormone], also decreased proinflammatory cytokine levels (interleukin-6, interleukin-8, tumor necrosis factor-α) of LP breeders (P < 0.05). The FMTHP group breeders had higher villus height, villus height/crypt depth ratio, and upregulated mRNA expression of jejunum barrier-related gene (ZO-2 and mucin-2) and estrogen, follicle-stimulating hormone (FSH) and anti-Müller hormone (AMH) receptor genes (ESR1, ESR2, FSHR, AMHR) (P < 0.05) than FMTCON group. FMT from HP donors led to higher mRNA expression of Bcl2 and sirtuin1 (SIRT1), while it downregulated the proapoptotic genes (Bax, caspase-3, caspase-8, and caspase-9) mRNA expressions in ovary compared with the FMTCON breeders (P < 0.05), and this pattern was also observed in HP donors. Also, HP breeder had higher observed_species and alpha-diversity indexes (Chao1 and ACE) than FMTCON group, while FMTHP can increase observed_species and alpha-diversity indexes (Chao1 and ACE) than FMTCON group (P < 0.05). The bacteria enrichment of Firmicutes (phylum), Bacteroidetes (phylum), Lactobacillus (genus), Enterococcus (genus), and Bacteroides (genus) were increased by FMTHP treatment. The genera Butyricicoccus, Enterococcus, and Lactobacillus were positively correlated with egg-laying rate. Therefore, cecal microbiomes of breeders with high egg-laying performance have more diverse activities, which may be related to the metabolism and health of the host; and FMT from high-yield donors can increase the hormone secretion, intestinal health, and ovarian function to improve egg-laying performance and the SIRT1-related apoptosis and cytokine signaling pathway were involved in this process.}, }
@article {pmid36681571, year = {2023}, author = {Ferre Aracil, C and El Hajra Martínez, I and Vera Mendoza, MS and Ramos Martínez, A and Muñez Rubio, E and Fernández-Cruz, A and Matallana Royo, V and García-Maseda, S and Sánchez Romero, I and Martínez Ruiz, R and Calleja Panero, JL}, title = {Faecal Microbiota Transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {41}, number = {4}, pages = {206-210}, doi = {10.1016/j.eimce.2022.01.004}, pmid = {36681571}, issn = {2529-993X}, mesh = {Humans ; Female ; Aged ; Male ; Fecal Microbiota Transplantation/methods ; *Clostridioides difficile ; Retrospective Studies ; Treatment Outcome ; Feces ; *Clostridium Infections ; }, abstract = {INTRODUCTION: Faecal microbiota transplantation (FMT) is a treatment supported by wide scientific evidence and proved to be very effective in the management of Clostridioides difficile infection (CDI). The objective of this study is to analyze its effectiveness and safety in a real clinical practice setting.<br><br>METHODS: Retrospective, single-center and descriptive observational study in which all FMT performed between May 2016 and December 2020 were included. Technical success was defined as the successful administration of the faecal preparation in the patient's gastrointestinal tract and clinical success the disappearance of diarrhoea in the first 72&#x202f;h after the procedure with no relapse within the following 8 weeks after the therapy was started.<br><br>RESULTS: 15 FMT were performed in 13 patients. Median age was 79 years (range: 40-98 years); being 60% women and 33.3% depedent persons. The indication for FMT was recurrent CDI in 84.6%. All FMTs were performed by colonoscopy and from related donors. With a first procedure, the FMT was effective in 11 of 13 patients (84.61%; 95% CI; 54.55-98.07). Time until resolution of symptoms was less than 48&#x202f;h in all cases. Post-transplant follow-up was 25.66&#x202f;&#xb1;&#x202f;17.5 months. No significant short or long-term complications were recorded at follow-up.<br><br>CONCLUSION: TMF is a simple, effective and safe procedure in CD infection, even in elderly patients or those with great comorbidities.}, }
@article {pmid36680756, year = {2023}, author = {Liu, Z and Wang, T and Zhu, Y and Zhao, H and Zhou, Z and Wu, Q}, title = {Improvements in Gut Microbiota Dysbiosis in Aged Mice Transplanted with Adipose-Derived Stem Cells.}, journal = {Stem cells and development}, volume = {32}, number = {7-8}, pages = {185-196}, doi = {10.1089/scd.2022.0257}, pmid = {36680756}, issn = {1557-8534}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Dysbiosis/therapy ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; Obesity/metabolism ; Stem Cells/metabolism ; }, abstract = {Adipose-derived stem cells (ASCs), as a cell therapy with considerable therapeutic potential, have received increasing attention in tissue repair, endocrine regulation, immune regulation, and aging and obesity research. Gut microbiota are present in all organisms and play important roles in the development of aging and obesity. Dysbiosis activates inflammatory pathways that may contribute to the development of aging and obesity. We used C57BL/6 J mice of different ages to carry out the experiment. Young mice were used as donors for ASC. Feces from the three groups were collected for 16sRNA sequencing to analyze the species composition of intestinal microorganisms, and then, predicted metabolic pathways by PICRUSt2 using 16s rRNA gene sequences. Immune cell levels in abdominal adipose tissue were assessed by flow cytometry. The content of IL-6, IL-1β, TNF-α, and lipopolysaccharides in serum was measured by ELISA kit. Our 16sRNA sequencing data showed restoration of gut microbiota diversity and an increase in beneficial flora (Akkermansia, Lactobacillus, Prevotella) 7 days after ASC transplantation. In addition, the inflammatory environment improved in older transplanted mice.}, }
@article {pmid36680641, year = {2023}, author = {Campos-Madueno, EI and Moradi, M and Eddoubaji, Y and Shahi, F and Moradi, S and Bernasconi, OJ and Moser, AI and Endimiani, A}, title = {Intestinal colonization with multidrug-resistant Enterobacterales: screening, epidemiology, clinical impact, and strategies to decolonize carriers.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {42}, number = {3}, pages = {229-254}, pmid = {36680641}, issn = {1435-4373}, support = {192514//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; 206400//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; }, mesh = {Humans ; *Drug Resistance, Multiple, Bacterial ; beta-Lactamases/genetics ; Klebsiella pneumoniae ; Escherichia coli ; Fecal Microbiota Transplantation ; Risk Factors ; *Gammaproteobacteria ; Anti-Bacterial Agents/pharmacology/therapeutic use ; }, abstract = {The clinical impact of infections due to extended-spectrum β-lactamase (ESBL)- and/or carbapenemase-producing Enterobacterales (Ent) has reached dramatic levels worldwide. Infections due to these multidrug-resistant (MDR) pathogens-especially Escherichia coli and Klebsiella pneumoniae-may originate from a prior asymptomatic intestinal colonization that could also favor transmission to other subjects. It is therefore desirable that gut carriers are rapidly identified to try preventing both the occurrence of serious endogenous infections and potential transmission. Together with the infection prevention and control countermeasures, any strategy capable of effectively eradicating the MDR-Ent from the intestinal tract would be desirable. In this narrative review, we present a summary of the different aspects linked to the intestinal colonization due to MDR-Ent. In particular, culture- and molecular-based screening techniques to identify carriers, data on prevalence and risk factors in different populations, clinical impact, length of colonization, and contribution to transmission in various settings will be overviewed. We will also discuss the standard strategies (selective digestive decontamination, fecal microbiota transplant) and those still in development (bacteriophages, probiotics, microcins, and CRISPR-Cas-based) that might be used to decolonize MDR-Ent carriers.}, }
@article {pmid36678326, year = {2023}, author = {Ma, X and Yan, H and Hong, S and Yu, S and Gong, Y and Wu, D and Li, Y and Xiao, H}, title = {Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice.}, journal = {Nutrients}, volume = {15}, number = {2}, pages = {}, pmid = {36678326}, issn = {2072-6643}, support = {81701367, 81901304//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; Mice, Obese ; *Adipocytes, Beige/metabolism ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Obesity/metabolism ; Lipids ; Firmicutes ; Mice, Inbred C57BL ; Diet, High-Fat ; }, abstract = {Given the increasing prevalence of obesity, the white-to-beige adipocyte conversion has attracted interest as a target for obesity treatment. Gamma-aminobutyric acid (GABA) treatment can reduce obesity, but the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism by which GABA triggers weight loss by improving the beiging of inguinal white adipose tissue (iWAT) and the role of gut microbiota in this process. The results showed that GABA reduced body weight and adipose inflammation and promoted the expression of thermogenic genes in the iWAT. The 16S rRNA sequence analysis of gut microbiota showed that GABA treatment increased the relative abundance of Bacteroidetes, Akkermansia, and Romboutsia and reduced that of Firmicutes and Erysipelatoclostridium in obese mice. Additionally, serum metabolomic analysis revealed that GABA treatment increased 3-hydroxybutyrate and reduced oxidized lipid levels in obese mice. Spearman's correlation analysis showed that Akkermansia and Romboutsia were negatively associated with the levels of oxidized lipids. Fecal microbiota transplantation analysis confirmed that the gut microbiota was involved in the white-to-beige adipocyte reconstruction by GABA. Overall, our findings suggest that GABA treatment may promote iWAT beiging through the gut microbiota in obese mice. GABA may be utilized to protect obese people against metabolic abnormalities brought on by obesity and gut dysbiosis.}, }
@article {pmid36678325, year = {2023}, author = {Daskova, N and Heczkova, M and Modos, I and Hradecky, J and Hudcovic, T and Kuzma, M and Pelantova, H and Buskova, I and Sticova, E and Funda, D and Golias, J and Drabonova, B and Jarkovska, J and Kralova, M and Cibulkova, I and Gojda, J and Cahova, M}, title = {Protective Effect of Vegan Microbiota on Liver Steatosis Is Conveyed by Dietary Fiber: Implications for Fecal Microbiota Transfer Therapy.}, journal = {Nutrients}, volume = {15}, number = {2}, pages = {}, pmid = {36678325}, issn = {2072-6643}, support = {grant NV-18-01-00040//Ministry of Health of the Czech Republic/ ; MH CR -DRO (IKEM - IN 00023001)//Ministry of Health of the Czech Republic/ ; Project No. LX22NPO5104//Programme EXCELES/ ; }, mesh = {Mice ; Animals ; Humans ; Fecal Microbiota Transplantation ; Vegans ; Inulin/pharmacology ; Dietary Fiber/pharmacology ; *Fatty Liver/prevention &amp; control/drug therapy ; *Gastrointestinal Microbiome ; Diet, Western ; Glucose/pharmacology ; }, abstract = {Fecal microbiota transfer may serve as a therapeutic tool for treating obesity and related disorders but currently, there is no consensus regarding the optimal donor characteristics. We studied how microbiota from vegan donors, who exhibit a low incidence of non-communicable diseases, impact on metabolic effects of an obesogenic diet and the potential role of dietary inulin in mediating these effects. Ex-germ-free animals were colonized with human vegan microbiota and fed a standard or Western-type diet (WD) with or without inulin supplementation. Despite the colonization with vegan microbiota, WD induced excessive weight gain, impaired glucose metabolism, insulin resistance, and liver steatosis. However, supplementation with inulin reversed steatosis and improved glucose homeostasis. In contrast, inulin did not affect WD-induced metabolic changes in non-humanized conventional mice. In vegan microbiota-colonized mice, inulin supplementation resulted in a significant change in gut microbiota composition and its metabolic performance, inducing the shift from proteolytic towards saccharolytic fermentation (decrease of sulfur-containing compounds, increase of SCFA). We found that (i) vegan microbiota alone does not protect against adverse effects of WD; and (ii) supplementation with inulin reversed steatosis and normalized glucose metabolism. This phenomenon is associated with the shift in microbiota composition and accentuation of saccharolytic fermentation at the expense of proteolytic fermentation.}, }
@article {pmid36677385, year = {2022}, author = {DuPont, HL and Jiang, ZD and Alexander, AS and DuPont, AW and Brown, EL}, title = {Intestinal IgA-Coated Bacteria in Healthy- and Altered-Microbiomes (Dysbiosis) and Predictive Value in Successful Fecal Microbiota Transplantation.}, journal = {Microorganisms}, volume = {11}, number = {1}, pages = {}, pmid = {36677385}, issn = {2076-2607}, abstract = {IgA-coated bacteria in the gut (IgA-biome) provide a homeostatic function in healthy people through inhibition of microbial invaders and by protecting the epithelial monolayer of the gut. The laboratory methods used to detect this group of bacteria require flow cytometry and DNA sequencing (IgA-Seq). With dysbiosis (reduced diversity of the microbiome), the IgA-biome also is impaired. In the presence of enteric infection, oral vaccines, or an intestinal inflammatory disorder, the IgA-biome focuses on the pathogenic bacteria or foreign antigens, while in other chronic diseases associated with dysbiosis, the IgA-biome is reduced in capacity. Fecal microbiota transplantation (FMT), the use of fecal product from well-screened, healthy donors administered to patients with dysbiosis, has been successful in engrafting the intestine with healthy microbiota and metabolites leading to improve health. Through FMT, IgA-coated bacteria have been transferred to recipients retaining their immune coating. The IgA-biome should be evaluated in FMT studies as these mucosal-associated bacteria are more likely to be associated with successful transplantation than free luminal organisms. Studies of the microbiome pre- and post-FMT should employ metagenomic methods that identify bacteria at least at the species level to better identify organisms of interest while allowing comparisons of microbiota data between studies.}, }
@article {pmid36674775, year = {2023}, author = {Przybyciński, J and Drożdżal, S and Wilk, A and Dziedziejko, V and Szumilas, K and Pawlik, A}, title = {The Effect of the Gut Microbiota on Transplanted Kidney Function.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36674775}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; Kidney ; *Kidney Transplantation/adverse effects ; Immunosuppressive Agents ; *Virus Diseases ; Bacteria ; }, abstract = {The intestinal microflora is extremely important, not only in the processes of absorption, digestion and biosynthesis of vitamins, but also in shaping the immune and cognitive functions of the human body. Several studies demonstrate a correlation between microbiota composition and such events as graft rejection, kidney interstitial fibrosis, urinary tract infections, and diarrhoea or graft tolerance. Some of those changes might be directly linked with pathologies such as colonization with pathogenic bacterial strains. Gut microbiota composition also plays an important role in metabolic complications and viral infections after transplantation. From the other side, gut microbiota might induce graft tolerance by promotion of T and B regulatory cells. Graft tolerance induction is still an extremely important issue regarding transplantology and might allow the reduction or even avoidance of immunosuppressive treatment. Although there is a rising evidence of the pivotal role of gut microbiota in aspects of kidney transplantation there is still a lack of knowledge on the direct mechanisms of microbiota action. Furthermore, some of those negative effects could be reversed by probiotics of faecal microbiota trapoinsplantation. While diabetes and hypertension as well as BKV and CMV viremia are common and important complications of transplantation, both worsening the graft function and causing systemic injuries, it opens up potential clinical treatment options. As has been also suggested in the current review, some bacterial subsets exhibit protective properties. However, currently, there is a lack of evidence on pro- and prebiotic supplementation in kidney transplant patients. In the current review, we describe the effect of the microbiota on the transplanted kidney in renal transplant recipients.}, }
@article {pmid36674517, year = {2023}, author = {Matheson, JT and Holsinger, RMD}, title = {The Role of Fecal Microbiota Transplantation in the Treatment of Neurodegenerative Diseases: A Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36674517}, issn = {1422-0067}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; *Microbiota ; *Clostridium Infections/therapy ; Dysbiosis/therapy ; }, abstract = {Neurodegenerative diseases are highly prevalent but poorly understood, and with few treatment options despite decades of intense research, attention has recently shifted toward other mediators of neurological disease that may present future targets for therapeutic research. One such mediator is the gut microbiome, which communicates with the brain through the gut-brain axis and has been implicated in various neurological disorders. Alterations in the gut microbiome have been associated with numerous neurological and other diseases, and restoration of the dysbiotic gut has been shown to improve disease conditions. One method of restoring a dysbiotic gut is via fecal microbiota transplantation (FMT), recolonizing the "diseased" gut with normal microbiome. Fecal microbiota transplantation is a treatment method traditionally used for Clostridium difficile infections, but it has recently been used in neurodegenerative disease research as a potential treatment method. This review aims to present a summary of neurodegenerative research that has used FMT, whether as a treatment or to investigate how the microbiome influences pathogenesis.}, }
@article {pmid36672796, year = {2022}, author = {Conti, G and D'Amico, F and Fabbrini, M and Brigidi, P and Barone, M and Turroni, S}, title = {Pharmacomicrobiomics in Anticancer Therapies: Why the Gut Microbiota Should Be Pointed Out.}, journal = {Genes}, volume = {14}, number = {1}, pages = {}, pmid = {36672796}, issn = {2073-4425}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics ; *Microbiota ; *Neoplasms/drug therapy ; }, abstract = {Anticancer treatments have shown a variable therapeutic outcome that may be partly attributable to the activity of the gut microbiota on the pathology and/or therapies. In recent years, microbiota-drug interactions have been extensively investigated, but most of the underlying molecular mechanisms still remain unclear. In this review, we discuss the relationship between the gut microbiota and some of the most commonly used drugs in oncological diseases. Different strategies for manipulating the gut microbiota layout (i.e., prebiotics, probiotics, antibiotics, and fecal microbiota transplantation) are then explored in order to optimize clinical outcomes in cancer patients. Anticancer technologies that exploit tumor-associated bacteria to target tumors and biotransform drugs are also briefly discussed. In the field of pharmacomicrobiomics, multi-omics strategies coupled with machine and deep learning are urgently needed to bring to light the interaction among gut microbiota, drugs, and host for the development of truly personalized precision therapies.}, }
@article {pmid36672518, year = {2022}, author = {Boicean, A and Neamtu, B and Birsan, S and Batar, F and Tanasescu, C and Dura, H and Roman, MD and Hașegan, A and Bratu, D and Mihetiu, A and Mohor, CI and Mohor, C and Bacila, C and Negrea, MO and Fleaca, SR}, title = {Fecal Microbiota Transplantation in Patients Co-Infected with SARS-CoV2 and Clostridioides difficile.}, journal = {Biomedicines}, volume = {11}, number = {1}, pages = {}, pmid = {36672518}, issn = {2227-9059}, support = {28PFE&#xa0;/&#xa0;30.12.2021//Ministerul Cercet&#x103;rii &#x219;i Inov&#x103;rii/ ; }, abstract = {Background: The COVID-19 pandemic has challenged the treatment of Clostridioides Difficile (CD)-infected patients given the increasing number of co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, fecal microbiota transplantation (FMT) shows promise in modulating the immune system’s function and alleviating the burdens associated with this condition. Methods: To achieve this goal, we performed a comparative, retrospective, single-center study on 86 patients (admitted between January 2020 and March 2022). We based our approach on specific inclusion criteria: 1. The study group included 46 co-infected patients (COVID-19 and CD) receiving antibiotics and FMT; 2. In the control group, 40 co-infected patients received antibiotics only. Our results showed no significant group differences in terms of gender, age, risk factors such as cardiovascular and neurological diseases, type 2 diabetes, and obesity (p > 0.05), or in pre-treatment inflammatory status, evaluated by white blood cell (WBC) count and C-reactive protein (CRP) levels. We report a significant decrease in inflammatory syndrome (CRP, WBC) in coinfected patients receiving FMT in addition to antibiotics (p < 0.05), with a lower relapse rate and mitigation of cramping and abdominal pain (91.3%). In addition, a higher level of fibrinogen, persistent moderate abdominal pain (82.5%), and a significantly higher CD infection relapse rate (42.5%) were recorded in co-infected patients treated only with antibiotics (p < 0.05). Conclusion: Our study provides new data to support the multiple benefits of FMT in the case of COVID-19 and CD co-infection by improving patients’ quality of life and inflammatory syndrome.}, }
@article {pmid36670104, year = {2023}, author = {Wang, J and Cao, Y and Hou, W and Bi, D and Yin, F and Gao, Y and Huang, D and Li, Y and Cao, Z and Yan, Y and Zhao, J and Kong, D and Lv, X and Huang, L and Zhong, H and Wu, C and Chen, Q and Yang, R and Wei, Q and Qin, H}, title = {Fecal microbiota transplantation improves VPA-induced ASD mice by modulating the serotonergic and glutamatergic synapse signaling pathways.}, journal = {Translational psychiatry}, volume = {13}, number = {1}, pages = {17}, pmid = {36670104}, issn = {2158-3188}, mesh = {Mice ; Animals ; *Autism Spectrum Disorder/chemically induced/therapy/metabolism ; Fecal Microbiota Transplantation ; Valproic Acid ; Dysbiosis/chemically induced/therapy ; Signal Transduction ; }, abstract = {Autism spectrum disorder (ASD) is a complex behavioral disorder diagnosed by social interaction difficulties, restricted verbal communication, and repetitive behaviors. Fecal microbiota transplantation (FMT) is a safe and efficient strategy to adjust gut microbiota dysbiosis and improve ASD-related behavioral symptoms, but its regulatory mechanism is unknown. The impact of the microbiota and its functions on ASD development is urgently being investigated to develop new therapeutic strategies for ASD. We reconstituted the gut microbiota of a valproic acid (VPA)-induced autism mouse model through FMT and found that ASD is in part driven by specific gut dysbiosis and metabolite changes that are involved in the signaling of serotonergic synapse and glutamatergic synapse pathways, which might be associated with behavioral changes. Further analysis of the microbiota showed a profound decrease in the genera Bacteroides and Odoribacter, both of which likely contributed to the regulation of serotonergic and glutamatergic synapse metabolism in mice. The engraftment of Turicibacter and Alistipes was also positively correlated with the improvement in behavior after FMT. Our results suggested that successful transfer of the gut microbiota from healthy donors to ASD mice was sufficient to improve ASD-related behaviors. Modulation of gut dysbiosis by FMT could be an effective approach to improve ASD-related behaviors in patients.}, }
@article {pmid36656870, year = {2023}, author = {Zhao, C and Bao, L and Zhao, Y and Wu, K and Qiu, M and Feng, L and Zhang, N and Hu, X and Fu, Y}, title = {A fiber-enriched diet alleviates Staphylococcus aureus-induced mastitis by activating the HDAC3-mediated antimicrobial program in macrophages via butyrate production in mice.}, journal = {PLoS pathogens}, volume = {19}, number = {1}, pages = {e1011108}, pmid = {36656870}, issn = {1553-7374}, mesh = {Animals ; Female ; Mice ; Anti-Bacterial Agents/pharmacology ; *Butyrates ; Diet ; Lactation ; Macrophages ; *Mastitis/therapy ; Staphylococcus aureus ; Dietary Fiber ; }, abstract = {Mounting evidence suggests that the gut microbiota plays an important role in the pathogenesis of mastitis, an important disease affecting the health of lactating women and the development of the dairy industry. However, the effect of the regulation of the gut microbiota by dietary components on mastitis development remains unknown. In this study, we found that a fiber-enriched diet alleviated Staphylococcus aureus (S. au)-induced mastitis in mice, which was dependent on the gut microbiota as depletion of the gut microbiota by antibiotics abolished this protective effect. Likewise, fecal microbiota transplantation (FMT) from high-inulin (HI)-treated mice (HIF) to recipient mice improved S. au-induced mastitis in mice. Consumption of an HI diet and HIF increased fecal short-chain fatty acid (SCFA) levels compared with the control group. Moreover, treatment with SCFAs, especially butyrate, alleviated S. au-induced mastitis in mice. Mechanistically, consumption of an HI diet enhanced the host antimicrobial program in macrophages through inhibiting histone deacetylase 3 by the production of butyrate. Collectively, our results suggest that modulation of the gut microbiota and its metabolism by dietary components is a potential strategy for mastitis intervention and serve as a basis for other infectious diseases.}, }
@article {pmid36656270, year = {2023}, author = {Gangwani, MK and Aziz, M and Aziz, A and Priyanka, F and Weissman, S and Phan, K and Dahiya, DS and Ahmed, Z and Sohail, AH and Lee-Smith, W and Kamal, F and Javaid, T and Nawras, A and Hart, B}, title = {Fresh Versus Frozen Versus Lyophilized Fecal Microbiota Transplant for Recurrent Clostridium Difficile Infection: A Systematic Review and Network Meta-analysis.}, journal = {Journal of clinical gastroenterology}, volume = {57}, number = {3}, pages = {239-245}, doi = {10.1097/MCG.0000000000001777}, pmid = {36656270}, issn = {1539-2031}, mesh = {Humans ; Fecal Microbiota Transplantation ; Network Meta-Analysis ; *Clostridioides difficile ; *Clostridium Infections/drug therapy ; Anti-Bacterial Agents/therapeutic use ; Treatment Outcome ; }, abstract = {INTRODUCTION: Clostridium difficile Infection is a significant source of morbidity and mortality, which is on the rise. Fecal Microbiota Transplantation (FMT) is an alternative therapy to antibiotics with a high success rate and low relapse rate. Current data regarding the efficacy of the types of FMT used, namely fresh, frozen, and lyophilized is conflicting. Our review attempts to consolidate this data and highlight the most efficacious treatment currently available.<br><br>METHODOLOGY: MEDLINE, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, SciELO, the Korean Citation Index, and Global Index Medicus were systematically searched from inception through May 3, 2022. Studies in which patients are undergoing any form of FMT who had failed antibiotic treatment previously were included. Both pairwise (direct) and network (direct + indirect) meta-analysis were performed using a random effects model and DerSimonian-Laird approach. A frequentist approach was used for network meta-analysis. Risk differences with (RD) with 95% confidence interval (CI) were calculated.<br><br>RESULTS: A total of 8 studies, including 4 RCTs and 4 cohort studies, were included with a total of 616 patients. Fresh FMT was determined to be most successful with 93% efficacy 95% CI (0.913 to 0.999) followed by frozen with 88% efficacy 95% CI (0.857 to 0.947) and lyophilized with 83% efficacy 95% CI (0.745 to 0.910). The direct meta-analysis showed no statistically significant difference between fresh and frozen group. (RD -0.051 95% CI -0.116 to 0.014 P =0.178). No significant differences were noted in frozen versus lyophilized groups with an overall trend towards Fresh FM (RD -0.061 95% CI -0.038 to 0.160 P =0.617). On network meta-analysis, when compared with fresh group, a lower recovery rate was noted with both frozen group (RD -0.06 95% CI -0.11 to 0.00 P =0.05) and lyophilized group (RD -0.16 95% CI -0.27 to -0.05 P =0.01).<br><br>CONCLUSION: We conclude the efficacy of Frozen and Lyophilized preparations is high with no difference in direct comparison, and the relative efficacy reduction based on network analysis is outweighed by the safety, accessibility, and practicality of Frozen or Lyophilized preparations.}, }
@article {pmid36654766, year = {2023}, author = {Hao, S and Yang, S and Zhang, N and Cheng, H}, title = {Fecal Microbiota Transplantation Research over the Past Decade: Current Status and Trends.}, journal = {The Canadian journal of infectious diseases &amp; medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale}, volume = {2023}, number = {}, pages = {6981721}, pmid = {36654766}, issn = {1712-9532}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a current research hotspot, with a surge in the output of publications over the past decade. This study dedicates to the exploration of the research status and highlights significant themes and future trends in FMT research with the aid of bibliometric analysis.<br><br>METHODS: FMT publications from 2012 to 2021 were retrieved on August 12, 2022, using the SCI-Expanded of Web of Science (WoS). The Bibliometrix in R program, Microsoft Office Excel, VOSviewer, and CiteSpace were utilized for bibliometrics and visual analysis, revealing the main publications, journals, countries, agencies, authors, and keywords distribution in FMT research.<br><br>RESULTS: There were 2,931 papers included. FMT research presented a growing trend from 2012 to 2021. The countries with the most publications and contributions in FMT area were China and the United States. The high-yield institutions were Harvard University, Udice French Research Universities, and the University of California System. The primary authors were Nieuwdorp Max, Allegretti Jessica R, and Kassam Zain. Frontiers in Microbiology and Science were the top-ranked journals in publications and total citations, respectively. The important topics primarily included FMT-related mechanisms and the usage of FMT in Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), metabolic disease, neurological disorders, and psychiatric disorders. Future research would primarily concentrate on neurological disorders, chemotherapy and immunotherapy for malignant tumors, and FMT-related consensus and guidelines.<br><br>CONCLUSION: With the help of bibliometric analysis, we were able to obtain the understanding of the status and trends of global FMT-related research. The field of FMT is undergoing tremendous progress, and our findings can guide clinical researchers' and practitioners' future work in the rapidly evolving field of FMT.}, }
@article {pmid36654598, year = {2022}, author = {Ferreira, A and Neves, MT and Baleiras, A and Malheiro, M and Martins, A}, title = {Fecal Microbiota Transplant in Immunotherapy-Resistant Melanoma: What Can We Expect in the Near Future?.}, journal = {Cureus}, volume = {14}, number = {12}, pages = {e32586}, pmid = {36654598}, issn = {2168-8184}, abstract = {Melanoma is a malignancy of melanocytes, melanin-producing cells in the basal layer of the epidermis. Despite representing only 1% of skin cancers, melanoma is responsible for over 80% of skin cancer deaths. Treatment with immune checkpoint inhibitors (ICIs) that target the programmed death 1 (PD-1) protein and the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways drastically transformed the management of patients with advanced melanoma. Before the introduction of ICIs, the average life expectancy for a patient with advanced melanoma ranged from six to 12 months, and now, this average survival has increased to over six years. However, despite this outstanding clinical success, most patients with advanced melanoma treated with ICIs will experience disease progression, immediately or after an initial response to treatment. Nowadays, some studies have looked at the mechanism behind the resistance to immunotherapy, with the aim of developing new treatments to overcome it. Emerging data suggest that gut microbiota (GM) influences response to immunotherapy. Importantly, unlike tumor genomics, the GM is changeable; thus, modulation of the GM is an attractive approach to overcome immunotherapy resistance. One of these approaches is the fecal microbiota transplant (FMT), which consists of the exchange of manipulated feces from a donor to a recipient who has a disorder related to intestinal dysbiosis to directly change the recipient's gut microbial composition and confer a health benefit. This review pretends to discuss the clinical benefit of FMT in the treatment of immunotherapy-resistant melanoma and potential adverse effects, including recent and ongoing clinical trials.}, }
@article {pmid36648505, year = {2023}, author = {Märtson, AG and da Silva Ferreira, AR and Veringa, A and Liu, L and Wardill, HR and Junier, LAT and van der Werf, TS and Harmsen, HJM and Sturkenboom, MGG and Span, LF and Tissing, WJE and Alffenaar, JC}, title = {Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study.}, journal = {Annals of hematology}, volume = {102}, number = {2}, pages = {421-427}, pmid = {36648505}, issn = {1432-0584}, support = {712660//H2020 Marie Sk&#x142;odowska-Curie Actions/ ; }, mesh = {Humans ; Middle Aged ; *Gastrointestinal Microbiome ; *Mucositis/chemically induced ; Pilot Projects ; Fluconazole/adverse effects ; Follow-Up Studies ; Prospective Studies ; Citrulline/pharmacology ; Stem Cell Transplantation ; *Anti-Infective Agents/adverse effects ; Ciprofloxacin/adverse effects ; }, abstract = {Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54-64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.}, }
@article {pmid36647403, year = {2023}, author = {Wakil, A and Niazi, M and Meybodi, MA and Pyrsopoulos, NT}, title = {Emerging Pharmacotherapies in Alcohol-Associated Hepatitis.}, journal = {Journal of clinical and experimental hepatology}, volume = {13}, number = {1}, pages = {116-126}, pmid = {36647403}, issn = {0973-6883}, abstract = {UNLABELLED: The incidence of alcoholic-associated hepatitis (AH) is increasing. The treatment options for severe AH (sAH) are scarce and limited to corticosteroid therapy which showed limited mortality benefit in short-term use only. Therefore, there is a dire need for developing safe and effective therapies for patients with sAH and to improve their high mortality rates.This review article focuses on the current novel therapeutics targeting various mechanisms in the pathogenesis of alcohol-related hepatitis. Anti-inflammatory agents such as IL-1 inhibitor, Pan-caspase inhibitor, Apoptosis signal-regulating kinase-1, and CCL2 inhibitors are under investigation. Other group of agents include gut-liver axis modulators, hepatic regeneration, antioxidants, and Epigenic modulators. We describe the ongoing clinical trials of some of the new agents for alcohol-related hepatitis.<br><br>CONCLUSION: A combination of therapies was investigated, possibly providing a synergistic effect of drugs with different mechanisms. Multiple clinical trials of novel therapies in AH remain ongoing. Their result could potentially make a difference in the clinical course of the disease. DUR-928 and granulocyte colony-stimulating factor had promising results and further trials are ongoing to evaluate their efficacy in the large patient sample.}, }
@article {pmid36641624, year = {2023}, author = {Uribe-Herranz, M and Beghi, S and Ruella, M and Parvathaneni, K and Salaris, S and Kostopoulos, N and George, SS and Pierini, S and Krimitza, E and Costabile, F and Ghilardi, G and Amelsberg, KV and Lee, YG and Pajarillo, R and Markmann, C and McGettigan-Croce, B and Agarwal, D and Frey, N and Lacey, SF and Scholler, J and Gabunia, K and Wu, G and Chong, E and Porter, DL and June, CH and Schuster, SJ and Bhoj, V and Facciabene, A}, title = {Modulation of the gut microbiota engages antigen cross-presentation to enhance antitumor effects of CAR T cell immunotherapy.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {31}, number = {3}, pages = {686-700}, pmid = {36641624}, issn = {1525-0024}, support = {R01 CA206012/CA/NCI NIH HHS/United States ; R01 CA219871/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; Receptors, Antigen, T-Cell/genetics ; Cross-Priming ; *Gastrointestinal Microbiome ; Vancomycin/pharmacology ; Immunotherapy ; T-Lymphocytes ; Immunotherapy, Adoptive/methods ; *Receptors, Chimeric Antigen/genetics ; Antigens, CD19 ; }, abstract = {Several studies have shown the influence of commensal microbes on T cell function, specifically in the setting of checkpoint immunotherapy for cancer. In this study, we investigated how vancomycin-induced gut microbiota dysbiosis affects chimeric antigen receptor (CAR) T immunotherapy using multiple preclinical models as well as clinical correlates. In two murine tumor models, hematopoietic CD19[+]-A20 lymphoma and CD19[+]-B16 melanoma, mice receiving vancomycin in combination with CD19-directed CAR T cell (CART-19) therapy displayed increased tumor control and tumor-associated antigens (TAAs) cross-presentation compared with CART-19 alone. Fecal microbiota transplant from human healthy donors to pre-conditioned mice recapitulated the results obtained in naive gut microbiota mice. Last, B cell acute lymphoblastic leukemia patients treated with CART-19 and exposed to oral vancomycin showed higher CART-19 peak expansion compared with unexposed patients. These results substantiate the role of the gut microbiota on CAR T cell therapy and suggest that modulation of the gut microbiota using vancomycin may improve outcomes after CAR T cell therapy across tumor types.}, }
@article {pmid36641024, year = {2023}, author = {Zhao, H and Li, M and Liu, L and Li, D and Zhao, L and Wu, Z and Zhou, M and Jia, L and Yang, F}, title = {Cordyceps militaris polysaccharide alleviates diabetic symptoms by regulating gut microbiota against TLR4/NF-κB pathway.}, journal = {International journal of biological macromolecules}, volume = {230}, number = {}, pages = {123241}, doi = {10.1016/j.ijbiomac.2023.123241}, pmid = {36641024}, issn = {1879-0003}, mesh = {Animals ; Mice ; NF-kappa B/metabolism ; Toll-Like Receptor 4/metabolism ; *Cordyceps/metabolism ; *Diabetes Mellitus, Type 2/drug therapy ; *Gastrointestinal Microbiome ; Polysaccharides/pharmacology ; }, abstract = {The relationship between gut microbiota and type 2 diabetes mellitus (T2DM) has attracted increasing attention. In our work, one purified fraction a (AEPSa) was obtained from Cordyceps militaris polysaccharides, and its hypoglycemic activity and underlying mechanisms were investigated in high-fat diet (HFD)- and streptozotocin (STZ)-induced T2DM mice. The results revealed that AEPSa reshaped gut microbiota by increasing Allobaculum, Alistipes, Lachnospiraceae_NK4A136_group and norank_f_Muribaculaceae and decreasing Enterococcus and Ruminococcus_torques_group to inhibit the colonic toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway and upregulate intestinal tight junction protein expression, thereby improving glucose and serum lipid metabolism, hormone secretion and complications. Fecal microbiota transplantation (FMT) also confirmed these findings. These results indicated that symptomatic relief of T2DM might be related to AEPSa regulating the gut microbiota against the TLR4/NF-κB pathway to protect the intestinal barrier. Therefore, AEPSa might be developed as a prebiotic agent against T2DM by regulating gut microbiota.}, }
@article {pmid36639024, year = {2023}, author = {Li, HY and Huang, SY and Zhou, DD and Xiong, RG and Luo, M and Saimaiti, A and Han, MK and Gan, RY and Zhu, HL and Li, HB}, title = {Theabrownin inhibits obesity and non-alcoholic fatty liver disease in mice via serotonin-related signaling pathways and gut-liver axis.}, journal = {Journal of advanced research}, volume = {52}, number = {}, pages = {59-72}, pmid = {36639024}, issn = {2090-1224}, mesh = {Mice ; Animals ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism/pathology ; Serotonin/pharmacology/therapeutic use ; RNA, Ribosomal, 16S ; Obesity/drug therapy/metabolism/microbiology ; Signal Transduction ; Tea ; }, abstract = {INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) with obesity seriously threats public health. Our previous studies showed that dark tea had more potential on regulating lipid metabolism than other teas, and theabrownin (TB) was considered to be a main contributor to the bioactivity of dark tea.<br><br>OBJECTIVES: This in vivo study aims to reveal the effects and molecular mechanisms of TB on NAFLD and obesity, and the role of the gut-liver axis is explored.<br><br>METHODS: The histopathological examinations, biochemical tests, and nuclear magnetic resonance were applied to evaluate the effects of TB on NAFLD and obesity. The untargeted metabolomics was used to find the key molecule for further exploration of molecular mechanisms. The 16S rRNA gene sequencing was used to assess the changes in gut microbiota. The antibiotic cocktail and fecal microbiota transplant were used to clarify the role of gut microbiota.<br><br>RESULTS: TB markedly reduced body weight gain (67.01%), body fat rate (62.81%), and hepatic TG level (51.35%) in the preventive experiment. Especially, TB decreased body weight (32.16%), body fat rate (42.56%), and hepatic TG level (42.86%) in the therapeutic experiment. The mechanisms of action could be the improvement of fatty acid oxidation, lipolysis, and oxidative stress via the regulation of serotonin-related signaling pathways. Also, TB increased the abundance of serotonin-related gut microbiota, such as Akkermansia, Bacteroides and Parabacteroides. Antibiotics-induced gut bacterial dysbiosis disrupted the regulation of TB on serotonin-related signaling pathways in liver, whereas the beneficial regulation of TB on target proteins was regained with the restoration of gut microbiota.<br><br>CONCLUSION: We find that TB has markedly preventive and therapeutic effects on NAFLD and obesity by regulating serotonin level and related signaling pathways through gut microbiota. Furthermore, gut microbiota and TB co-contribute to alleviating NAFLD and obesity. TB could be a promising medicine for NAFLD and obesity.}, }
@article {pmid36638854, year = {2023}, author = {Guo, HH and Shen, HR and Tang, MZ and Sheng, N and Ding, X and Lin, Y and Zhang, JL and Jiang, JD and Gao, TL and Wang, LL and Han, YX}, title = {Microbiota-derived short-chain fatty acids mediate the effects of dengzhan shengmai in ameliorating cerebral ischemia via the gut-brain axis.}, journal = {Journal of ethnopharmacology}, volume = {306}, number = {}, pages = {116158}, doi = {10.1016/j.jep.2023.116158}, pmid = {36638854}, issn = {1872-7573}, mesh = {Rats ; Animals ; Brain-Gut Axis ; Phosphatidylinositol 3-Kinases ; *Brain Ischemia ; *Microbiota ; Fatty Acids, Volatile/metabolism ; Cerebral Infarction ; }, abstract = {Dengzhan shengmai (DZSM) formula, composed of four herbal medicines (Erigeron breviscapus, Panax ginseng, Schisandra chinensis, and Ophiopogon japonicus), is widely used in the recovery period of ischemic cerebrovascular diseases; however, the associated molecular mechanism remains unclear.<br><br>AIM OF THE STUDY: The purpose of this study was to uncover the links between the microbiota-gut-brain axis and the efficacy of DZSM in ameliorating cerebral ischemic diseases.<br><br>MATERIALS AND METHODS: The effects of DZSM on the gut microbiota community and bacteria-derived short-chain fatty acid (SCFA) production were evaluated in vivo using a rat model of cerebral ischemia and in vitro through the anaerobic incubation with fresh feces derived from model animals. Subsequently, the mechanism underlying the role of SCFAs in the DZSM-mediated treatment of cerebral ischemia was explored.<br><br>RESULTS: We found that DZSM treatment significantly altered the composition of the gut microbiota and markedly enhanced SCFA production. The consequent increase in SCFA levels led to the upregulation of the expression of monocarboxylate transporters and facilitated the transportation of intestinal SCFAs into the brain, thereby inhibiting the apoptosis of neurocytes via the regulation of the PI3K/AKT/caspase-3 pathway. The increased intestinal SCFA levels also contributed to the repair of the 2VO-induced disruption of gut barrier integrity and inhibited the translocation of lipopolysaccharide from the intestine to the brain, thus attenuating neuroinflammation. Consequently, cerebral neuropathy and oxidative stress were significantly improved in 2VO model rats, leading to the amelioration of cerebral ischemia-induced cognitive dysfunction. Finally, fecal microbiota transplantation could reproduce the beneficial effects of DZSM on SCFA production and cerebral ischemia.<br><br>CONCLUSIONS: Our findings suggested that SCFAs mediate the effects of DZSM in ameliorating cerebral ischemia via the gut microbiota-gut-brain axis.}, }
@article {pmid36638713, year = {2023}, author = {Wang, Z and Sun, Y and Han, Y and Chen, X and Gong, P and Zhai, P and Yao, W and Ba, Q and Wang, H}, title = {Eucommia bark/leaf extract improves HFD-induced lipid metabolism disorders via targeting gut microbiota to activate the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {110}, number = {}, pages = {154652}, doi = {10.1016/j.phymed.2023.154652}, pmid = {36638713}, issn = {1618-095X}, mesh = {Mice ; Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Lipid Metabolism ; *Eucommiaceae/chemistry ; Lipoprotein Lipase ; Plant Bark ; Liver ; Fatty Acids, Volatile/metabolism ; Plant Extracts/therapeutic use ; *Lipid Metabolism Disorders/drug therapy/metabolism ; }, abstract = {BACKGROUND: The bark of Eucommia ulmoides (a perennial deciduous tree termed eucommia hereafter) has anti-hyperlipidemia effects due to its bioactive components. However, the slow growth of eucommia bark leads to a deficit in this resource. Studies have shown that eucommia leaf has bioactive components similar to those of eucommia bark and anti-hyperlipidemia effects. At present, the strength of the anti-hyperlipidemia effect of eucommia bark and eucommia leaf has not been reported. Their interaction with the gut microbiota and the mechanism by which the gut microbiota exerts anti-hyperlipidemia effects are unclear.<br><br>PURPOSES: Through fecal microbiota transplantation (FMT) experiments, this study aimed to investigate the mechanism by which fecal bacteria suspensions containing chlorogenic acid (CGA), eucommia bark extract (EBE), and eucommia leaves extract (ELE) improve high-fat diet (HFD)-induced lipid metabolism disorders. Difference in anti-hyperlipidemia effects between EBE and ELE and exploring an eucommia bark substitute to improve the sustainable utilization of eucommia were also evaluated.<br><br>RESULTS: EBE and ELE contain eight identical bioactive ingredients, and fecal bacteria suspensions containing EBE and ELE significantly improved HFD-induced lipid metabolism disorders and elevated blood glucose levels. The fecal bacteria suspension of healthy mice containing CGA, EBE, and ELE significantly reduced the relative abundance of Erysipelothrichaceae and Ruminococcaceae and promoted short chain fatty acids (SCFAs) production thereby activating the expression of the SCFA. G protein-coupled receptor 43 (GPR43) gene in colon and epididymal fat tissues. In addition, fecal bacteria suspensions of healthy mice containing CGA, EBE, or ELE significantly activated fasting-induced adipose factor (Fiaf) gene expression in colon tissue and inhibited the secretion of lipoprotein lipase (LPL) in liver tissue, thereby inhibiting the synthesis of triglycerides (TG). Changed in the Erysipelotrichaceae and Ruminococcaceae relative abundances were significantly correlated with these target genes. Thus, regulating the abundance of the Erysipelotrichaceae and Ruminococcaceae could serve as a potential target for the role of fecal bacteria suspensions of healthy mice containing CGA, EBE, or ELE in the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis. In addition, regarding HFD-induced lipid metabolism disorders and gut microbiota structural disorders, we found no significant difference between ELE and EBE.<br><br>CONCLUSIONS: Our FMT experiments evidenced that EBE and ELE improve lipid metabolism disorders by regulating the gut microbiota, providing a new pathway for treating hyperlipidemia using eucommia dietary therapy. There was no significant difference in the anti-hyperlipidemia effects of ELE and EBE; thus, eucommia leaf could replace eucommia bark in traditional Chinese medicine, so as to achieve a sustainable utilization of eucommia resources.}, }
@article {pmid36638348, year = {2023}, author = {Zeng, X and Li, X and Li, X and Wei, C and Shi, C and Hu, K and Kong, D and Luo, Q and Xu, Y and Shan, W and Zhang, M and Shi, J and Feng, J and Han, Y and Huang, H and Qian, P}, title = {Fecal microbiota transplantation from young mice rejuvenates aged hematopoietic stem cells by suppressing inflammation.}, journal = {Blood}, volume = {141}, number = {14}, pages = {1691-1707}, pmid = {36638348}, issn = {1528-0020}, support = {S10 OD026983/OD/NIH HHS/United States ; S10 OD030269/OD/NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Fecal Microbiota Transplantation ; *Hematopoietic Stem Cells/metabolism ; Inflammation/therapy/metabolism ; Cell Differentiation ; Hematopoiesis ; }, abstract = {Hematopoietic stem cell (HSC) aging is accompanied by hematopoietic reconstitution dysfunction, including loss of regenerative and engraftment ability, myeloid differentiation bias, and elevated risks of hematopoietic malignancies. Gut microbiota, a key regulator of host health and immunity, has recently been reported to affect hematopoiesis. However, there is currently limited empirical evidence explaining the direct impact of gut microbiome on aging hematopoiesis. In this study, we performed fecal microbiota transplantation (FMT) from young mice to aged mice and observed a significant increment in lymphoid differentiation and decrease in myeloid differentiation in aged recipient mice. Furthermore, FMT from young mice rejuvenated aged HSCs with enhanced short-term and long-term hematopoietic repopulation capacity. Mechanistically, single-cell RNA sequencing deciphered that FMT from young mice mitigated inflammatory signals, upregulated the FoxO signaling pathway, and promoted lymphoid differentiation of HSCs during aging. Finally, integrated microbiome and metabolome analyses uncovered that FMT reshaped gut microbiota composition and metabolite landscape, and Lachnospiraceae and tryptophan-associated metabolites promoted the recovery of hematopoiesis and rejuvenated aged HSCs. Together, our study highlights the paramount importance of the gut microbiota in HSC aging and provides insights into therapeutic strategies for aging-related hematologic disorders.}, }
@article {pmid36637229, year = {2023}, author = {Green, JE and Berk, M and Mohebbi, M and Loughman, A and McGuinness, AJ and Castle, D and Chatterton, ML and Perez, J and Strandwitz, P and Athan, E and Hair, C and Nierenberg, AA and Cryan, JF and Jacka, F}, title = {Feasibility, Acceptability, and Safety of Faecal Microbiota Transplantation in the Treatment of Major Depressive Disorder: A Pilot Randomized Controlled Trial.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {68}, number = {5}, pages = {315-326}, pmid = {36637229}, issn = {1497-0015}, mesh = {Adult ; Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Depressive Disorder, Major/therapy ; Pilot Projects ; Feasibility Studies ; Quality of Life ; Treatment Outcome ; Double-Blind Method ; }, abstract = {OBJECTIVES: Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD.<br><br>METHODS: The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial (n = 15) of enema-delivered FMT (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD.<br><br>RESULTS: Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful; nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD.<br><br>CONCLUSIONS: All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.}, }
@article {pmid36636378, year = {2023}, author = {Guan, X and Sun, Z}, title = {The Role of Intestinal Flora and Its Metabolites in Heart Failure.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {51-64}, pmid = {36636378}, issn = {1178-6973}, abstract = {Intestinal flora is a complex collection of microbial communities that participate in the physiological and pathological activities of the human body through various pathways. In recent years, numerous studies have reported that intestinal flora are involved in the occurrence and development of heart failure (HF) and its metabolic products could play an important role in this progression, suggesting a great value in the clinical treatment of this condition. This study reported the interaction between intestinal flora and HF, and with intestinal flora metabolites, such as short-chain fatty acids, trimethylamine N-oxide and bile acids and urotoxins, considered as the starting point, the mechanism of the roles in HF was summarized. Additionally, the current research status and the development prospects of applying flora and metabolites to the clinical therapeutic decision of HF were discussed.}, }
@article {pmid36632334, year = {2022}, author = {Wexler, A}, title = {Mapping the Landscape of Do-it-Yourself Medicine.}, journal = {Citizen science : theory and practice}, volume = {7}, number = {1}, pages = {}, pmid = {36632334}, issn = {2057-4991}, support = {DP5 OD026420/OD/NIH HHS/United States ; }, abstract = {The practice of medicine is typically conceptualized as remaining within the boundaries of a hospital or clinic. However, in recent years, patients have been able to gain access to information about medical research as it is ongoing. As a result, there has been a rise in do-it-yourself (DIY) medicine, where individuals treat themselves for medical conditions outside of clinical settings, often mimicking experimental therapies that remain inaccessible to the wider public. For example, in DIY brain stimulation, individuals suffering from depression build at-home electrical headsets using nine-volt batteries, mimicking an experimental neuroscience technique used in scientific laboratories. In DIY fecal transplantation, those with intestinal disorders like C. Difficile and inflammatory bowel disease transplant stool from donors into themselves with the aid of blenders and enemas. In the open Artificial Pancreas System movement, diabetes patients hacked together an artificial pancreas system from their glucose monitors and insulin pumps, years before such a system was approved by the United States Food and Drug Administration (US FDA). To date, scholarship on DIY medicine has largely been relegated to specific medical domains (e.g., neurology, gastroenterology, infectious disease). In this paper, however, I recognize DIY medicine as a cross-cutting phenomenon that has emerged independently across medical domains but shares common features. I map the varieties of DIY medicine across these domains and suggest that four key factors lead to their creation, growth, and uptake. In doing so, this essay sheds light on an understudied area of biomedical citizen science that is likely to grow substantially in the coming decades.}, }
@article {pmid36632246, year = {2022}, author = {Patel, M and Atluri, LM and Gonzalez, NA and Sakhamuri, N and Athiyaman, S and Randhi, B and Gutlapalli, SD and Pu, J and Zaidi, MF and Khan, S}, title = {A Systematic Review of Mixed Studies Exploring the Effects of Probiotics on Gut-Microbiome to Modulate Therapy in Children With Autism Spectrum Disorder.}, journal = {Cureus}, volume = {14}, number = {12}, pages = {e32313}, pmid = {36632246}, issn = {2168-8184}, abstract = {Autism spectrum disorder(ASD) is a complex neurodevelopmental disorder characterized by social deficits, repetitive typical behaviors, insistence on the same routines, and communication impairments. The prevalence of ASD has increased in the past decade. While we are aware that there is no cure for ASD, attempts are being made to reduce its symptoms and improve the learning, overall growth, and well-being of ASD patients. Gastrointestinal (GI) symptoms are frequent occurrences in patients with ASD, but the underlying mechanisms are unknown. Recent studies show that the microbiota-gut-brain axis is the key modulator of neuropsychiatric health. Although fecal transplants have shown positive outcomes in treating dysbiosis and symptoms of autism, lifestyle modifications such as dietary intervention will prevent and treat this disorder without causing major adverse effects. Probiotics enhance the microbiome to provide necessary metabolites, which help in gut permeability, cognitive function, and immunity. In some studies, children with increased GI symptoms have also shown increased behavioral disturbances. In this study, a systematic review of mixed studies is conducted to obtain more robust and conclusive results. We included randomized controlled studies with larger sample sizes and specifications on probiotics.}, }
@article {pmid36631604, year = {2023}, author = {Mei, T and Noguchi, H and Kuraji, R and Kubo, S and Sato, Y and Kaku, K and Okabe, Y and Onishi, H and Nakamura, M}, title = {Effects of periodontal pathogen-induced intestinal dysbiosis on transplant immunity in an allogenic skin graft model.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {544}, pmid = {36631604}, issn = {2045-2322}, mesh = {*Dysbiosis/complications/microbiology ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome ; Inflammation/pathology ; *Periodontal Diseases/complications/microbiology ; Porphyromonas gingivalis ; *Skin Transplantation ; Intestines/microbiology/pathology ; Mice ; *Graft Rejection/immunology/microbiology ; Animals ; }, abstract = {Periodontal disease can induce dysbiosis, a compositional and functional alteration in the microbiota. Dysbiosis induced by periodontal disease is known to cause systemic inflammation and may affect transplant immunity. Here, we examined the effects of periodontal disease-related intestinal dysbiosis on transplant immunity using a mouse model of allogenic skin graft in which the mice were orally administered the periodontal pathogen Porphyromonas gingivalis (Pg). For 6 weeks, the Pg group orally received Pg while the control group orally received phosphate-buffered saline solution. After that, both groups received allogenic skin grafts. 16 s rRNA analysis of feces revealed that oral administration of Pg significantly increased three short chain fatty acids (SCFAs) producing genera. SCFA (acetate and propionate) levels were significantly higher in the Pg group (p = 0.040 and p = 0.005). The ratio of regulatory T cells, which are positively correlated with SCFAs, to total CD4+ T cells in the peripheral blood and spleen was significantly greater (p = 0.002 and p < 0.001) in the Pg group by flowcytometry. Finally, oral administration of Pg significantly prolonged skin graft survival (p < 0.001) and reduced pathological inflammation in transplanted skin grafts. In conclusion, periodontal pathogen-induced intestinal dysbiosis may affect transplant immunity through increased levels of SCFAs and regulatory T cells. (198 words).}, }
@article {pmid36631533, year = {2023}, author = {Shrode, RL and Knobbe, JE and Cady, N and Yadav, M and Hoang, J and Cherwin, C and Curry, M and Garje, R and Vikas, P and Sugg, S and Phadke, S and Filardo, E and Mangalam, AK}, title = {Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {526}, pmid = {36631533}, issn = {2045-2322}, support = {P30 ES005605/ES/NIEHS NIH HHS/United States ; T32 GM139776/GM/NIGMS NIH HHS/United States ; I01 CX002212/CX/CSRD VA/United States ; R01 AI137075/AI/NIAID NIH HHS/United States ; P30 CA086862/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; United States/epidemiology ; Female ; *Breast Neoplasms ; Dysbiosis/microbiology ; Bacteria/genetics ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics/analysis ; }, abstract = {As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment.}, }
@article {pmid36631439, year = {2023}, author = {Yuan, X and Zhou, F and Wang, H and Xu, X and Xu, S and Zhang, C and Zhang, Y and Lu, M and Zhang, Y and Zhou, M and Li, H and Zhang, X and Zhang, T and Song, J}, title = {Systemic antibiotics increase microbiota pathogenicity and oral bone loss.}, journal = {International journal of oral science}, volume = {15}, number = {1}, pages = {4}, pmid = {36631439}, issn = {2049-3169}, mesh = {Humans ; Mice ; Animals ; Dysbiosis ; Anti-Bacterial Agents/pharmacology ; Virulence ; *Microbiota ; *Periodontitis/chemically induced ; Cytokines ; }, abstract = {Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.}, }
@article {pmid36629092, year = {2023}, author = {Thacher, PR and Kendrick, EL and Maslanka, M and Muletz-Wolz, CR and Bornbusch, SL}, title = {Fecal microbiota transplants modulate the gut microbiome of a two-toed sloth (Choloepus didactylus).}, journal = {Zoo biology}, volume = {42}, number = {3}, pages = {453-458}, doi = {10.1002/zoo.21751}, pmid = {36629092}, issn = {1098-2361}, mesh = {Humans ; Animals ; Fecal Microbiota Transplantation/veterinary/methods ; *Gastrointestinal Microbiome ; *Sloths ; Animals, Zoo ; Feces ; }, abstract = {The microbes inhabiting an animal's gastrointestinal tracts, collectively known as the gut microbiome, are vital to animal health and wellbeing. For animals experiencing gut distress or infection, modulation of the gut microbiome, for example, via fecal microbiota transplant (FMT), provides a possible disease prevention and treatment method. The beneficial microbes present in the donor's transplanted feces can help combat pathogens, assist in digestion, and rebalance the recipient's microbiota. Investigating the efficacy of FMTs in animal health is a crucial step toward improving management strategies for species under human care. We present a case study of the use of FMTs in a two-toed sloth experiencing abnormally large, clumped, and frequent stools. We used 16 S rRNA amplicon sequencing of fecal samples to (a) compare the microbiomes of the FMT donor, a healthy, cohoused conspecific, and the FMT recipient and (b) assess the influence of multiple rounds of FMTs on the recipient's microbiome and stool consistency and frequency over time. In response to the FMTs, we found that the recipient's microbiome showed trends toward increased diversity, shifted community composition, and altered membership that more resembled the community of the donor. FMT treatment was also associated with marked, yet temporary, alleviation of the recipient's abnormal bowel movements, suggesting a broader impact on gut health. Our results provide valuable preliminary evidence that FMT treatments can augment the recipient's gut microbiome, with potential implications for animal health and management.}, }
@article {pmid36627937, year = {2022}, author = {Yu, J and Cheon, JH}, title = {Microbial Modulation in Inflammatory Bowel Diseases.}, journal = {Immune network}, volume = {22}, number = {6}, pages = {e44}, pmid = {36627937}, issn = {1598-2629}, abstract = {Gut dysbiosis is one of prominent features in inflammatory bowel diseases (IBDs) which are of an unknown etiology. Although the cause-and-effect relationship between IBD and gut dysbiosis remains to be elucidated, one area of research has focused on the management of IBD by modulating and correcting gut dysbiosis. The use of antibiotics, probiotics either with or without prebiotics, and fecal microbiota transplantation from healthy donors are representative methods for modulating the intestinal microbiota ecosystem. The gut microbiota is not a simple assembly of bacteria, fungi, and viruses, but a complex organ-like community system composed of numerous kinds of microorganisms. Thus, studies on specific changes in the gut microbiota depending on which treatment option is applied are very limited. Here, we review previous studies on microbial modulation as a therapeutic option for IBD and its significance in the pathogenesis of IBD.}, }
@article {pmid36627827, year = {2023}, author = {Li, ZM and Kong, CY and Mao, YQ and Huang, JT and Chen, HL and Han, B and Wang, LS}, title = {Ampicillin exacerbates acetaminophen-induced acute liver injury by inducing intestinal microbiota imbalance and butyrate reduction.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {43}, number = {4}, pages = {865-877}, doi = {10.1111/liv.15512}, pmid = {36627827}, issn = {1478-3231}, mesh = {Animals ; Mice ; Acetaminophen/toxicity ; *Gastrointestinal Microbiome ; Butyrates/pharmacology ; Liver ; Ampicillin/adverse effects ; *Chemical and Drug Induced Liver Injury/etiology ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND AND AIMS: Antibiotics (ATBx) and acetaminophen (APAP) are widely used worldwide. APAP is the most common cause of acute liver injury (ALI) and might be used in combination with ATBx in clinics. However, the impact of ATBx on APAP-induced ALI has rarely been studied.<br><br>METHODS: First, we compared the effects of seven ATBx on APAP-induced ALI. Then, we analysed faecal, serum and liver samples to investigate the impact of the gut microbiota on this process. Finally, we assessed the role of short-chain fatty acids in this process.<br><br>RESULTS: In this work, we found that the ALI was significantly aggravated in the mice treated with ampicillin (Amp) instead of other ATBx. Amp exposure reduced the diversity and altered the composition of gut microbiota. The altered gut microbiota aggravated APAP-induced ALF, which was proven by faecal microbiota transplantation from ATBx-treated mice. Metagenomic analysis showed a significantly decreased Lactobacillus abundance in Amp-treated mice. Gavage with Lactobacillus, especially Lactobacillus rhamnosus, significantly reversed the severer ALF induced by APAP and Amp. Moreover, Lactobacillus supplementation increased butyrate-producing clostridia and lowered butyrate levels in Amp-treated mice. In accordance, butyrate supplementation could also alleviate Amp-aggravated ALI. In addition, inhibition of nuclear factor erythroid 2-related factor 2 counteracted the protective effect of butyrate on aggravated ALI induced by Amp and APAP.<br><br>CONCLUSION: Together, this study revealed a potential health impact of Amp that may exacerbate liver damage when co-exposed to excess APAP.}, }
@article {pmid36627762, year = {2023}, author = {Su, SH and Chen, M and Wu, YF and Lin, Q and Wang, DP and Sun, J and Hai, J}, title = {Fecal microbiota transplantation and short-chain fatty acids protected against cognitive dysfunction in a rat model of chronic cerebral hypoperfusion.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {29 Suppl 1}, number = {Suppl 1}, pages = {98-114}, pmid = {36627762}, issn = {1755-5949}, support = {81601146//National Natural Science Foundation of China/ ; 81771410//National Natural Science Foundation of China/ ; 81902521//National Natural Science Foundation of China/ ; 81974209//National Natural Science Foundation of China/ ; 19YF1432800//Shanghai Sailing Program/ ; }, mesh = {Rats ; Animals ; Fecal Microbiota Transplantation/methods ; Feces/chemistry ; Fatty Acids, Volatile/analysis ; *Brain Ischemia/therapy ; *Cognitive Dysfunction/etiology/therapy ; }, abstract = {AIMS: Clear roles and mechanisms in explaining gut microbial dysbiosis and microbial metabolites short-chain fatty acids (SCFAs) alterations in chronic cerebral ischemic pathogenesis have yet to be explored. In this study, we investigated chronic cerebral hypoperfusion (CCH)-induced gut microbiota and metabolic profiles of SCFAs as well as the effects and mechanisms of fecal microbiota transplantation (FMT) and SCFAs treatment on CCH-induced hippocampal neuronal injury.<br><br>METHODS: Bilateral common carotid artery occlusion (BCCAo) was used to establish the CCH model. Gut microbiota and SCFAs profiles in feces and hippocampus were evaluated by 16S ribosomal RNA sequencing and gas chromatography-mass spectrometry. RNA sequencing analysis was performed in hippocampal tissues. The potential molecular pathways and differential genes were verified through western blot, immunoprecipitation, immunofluorescence, and ELISA. Cognitive function was assessed via the Morris water maze test. Ultrastructures of mitochondria and synapses were tested through a transmission electron microscope.<br><br>RESULTS: Chronic cerebral hypoperfusion induced decreased fecal acetic and propionic acid and reduced hippocampal acetic acid, which were reversed after FMT and SCFAs administration by changing fecal microbial community structure and compositions. Furthermore, in the hippocampus, FMT and SCFAs replenishment exerted anti-neuroinflammatory effects through inhibiting microglial and astrocytic activation as well as switching microglial phenotype from M1 toward M2. Moreover, FMT and SCFAs treatment alleviated neuronal loss and microglia-mediated synaptic loss and maintained the normal process of synaptic vesicle fusion and release, resulting in the improvement of synaptic plasticity. In addition, FMT and SCFAs supplement prevented oxidative phosphorylation dysfunction via mitochondrial metabolic reprogramming. The above effects of FMT and SCFAs treatment led to the inhibition of CCH-induced cognitive impairment.<br><br>CONCLUSION: Our findings highlight FMT and SCFAs replenishment would be the feasible gut microbiota-based strategy to mitigate chronic cerebral ischemia-induced neuronal injury.}, }
@article {pmid36627187, year = {2023}, author = {Pinto, Y and Frishman, S and Turjeman, S and Eshel, A and Nuriel-Ohayon, M and Shrossel, O and Ziv, O and Walters, W and Parsonnet, J and Ley, C and Johnson, EL and Kumar, K and Schweitzer, R and Khatib, S and Magzal, F and Muller, E and Tamir, S and Tenenbaum-Gavish, K and Rautava, S and Salminen, S and Isolauri, E and Yariv, O and Peled, Y and Poran, E and Pardo, J and Chen, R and Hod, M and Borenstein, E and Ley, RE and Schwartz, B and Louzoun, Y and Hadar, E and Koren, O}, title = {Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.}, journal = {Gut}, volume = {72}, number = {5}, pages = {918-928}, pmid = {36627187}, issn = {1468-3288}, support = {R01 HD063142/HD/NICHD NIH HHS/United States ; }, mesh = {Pregnancy ; Female ; Humans ; *Diabetes, Gestational/diagnosis ; *Microbiota ; Pregnancy Trimester, Third ; Inflammation ; Cytokines ; }, abstract = {OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities.<br><br>DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394&#x2009;women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts.<br><br>RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy.<br><br>CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.}, }
@article {pmid36627028, year = {2023}, author = {Zhang, S and Zeng, L and Ma, J and Xu, W and Qu, Y and Wang, X and An, X and Wang, Q and Wu, Y and Wang, D and Chen, H and Ai, J}, title = {Gut Prevotellaceae-GABAergic septohippocampal pathway mediates spatial memory impairment in high-fat diet-fed ovariectomized mice.}, journal = {Neurobiology of disease}, volume = {177}, number = {}, pages = {105993}, doi = {10.1016/j.nbd.2023.105993}, pmid = {36627028}, issn = {1095-953X}, mesh = {Female ; Mice ; Animals ; *Spatial Memory ; *Diet, High-Fat/adverse effects ; Quality of Life ; Resistant Starch/metabolism/pharmacology ; Hippocampus/metabolism ; GABAergic Neurons/metabolism ; Theta Rhythm/physiology ; }, abstract = {Clarifying the risk factors and mechanisms that contribute to the onset of cognitive impairment following estrogen depletion is essential for improving the quality of life of older females. In the current study, using behavioral tests, 16S rDNA sequencing, in vivo and in vitro electrophysiology, optogenetics and chemogenetics, we found that high-fat diet (HFD)-accelerated impairment of hippocampus-dependent memory, gut microbiota, and hippocampal theta rhythmogenesis in ovariectomized (OVX) mice and fecal microbiota transplantation rescued these phenomena. The identification of fasting-activated medial septal neurons showed that PV[+] GABAergic neurons in the medial septal area (MSA) respond to gut sensory signals. Optogenetic activation of septohippocampal PV[+] GABAergic fibers (but not cholinergic fibers) significantly rescued hippocampal theta rhythmogenesis and spatial memory in HFD-fed OVX mice. Resistant starch supplementation (RSHFD) rectified the gut Prevotellaceae and considerably alleviated reduced septal gut-responsive neurons, decreased hippocampal theta rhythm, and impaired hippocampus-dependent memory in HFD-fed OVX mice. Furthermore, chemogenetic inhibition of septal PV[+] GABAergic neurons reversed the neuroprotective effects of resistant starch supplementation. These findings highlight the notable gut-sensory nature of medial septal PV[+] GABAergic neurons. A HFD accelerates estrogen deficiency-induced cognitive impairment by disrupting the gut Prevotellaceae-septo-hippocampal pathway. This study contributes to a better understanding of the precise gut-brain control of cognition and cognitive impairment in postmenopausal females.}, }
@article {pmid36626083, year = {2023}, author = {Wang, W and Yan, Y and Yu, F and Zhang, W and Su, S}, title = {Role of oral and gut microbiota in childhood obesity.}, journal = {Folia microbiologica}, volume = {68}, number = {2}, pages = {197-206}, pmid = {36626083}, issn = {1874-9356}, mesh = {Humans ; Child ; *Pediatric Obesity/therapy ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; *Probiotics/therapeutic use ; *Microbiota ; }, abstract = {Childhood obesity not only causes damage to children's respiratory, cardiovascular, endocrine, motor, and other systems but also is a significant risk factor for metabolic diseases such as obesity in adulthood, which has become one of the serious public health problems worldwide. The etiology and pathogenesis of obesity are complex. In addition to genetic and lifestyle factors, recent studies have found that the microbes in the digestive tract play a crucial role in the occurrence and development of obesity. Among them, the gut microbiota has been confirmed to be one of the important pathogenic factors of obesity, which can mediate the occurrence and development of obesity by interfering with the balance of host energy metabolism and inducing low-grade chronic inflammation throughout the host. Targeting the gut microbiota to treat obesity through various methods such as fecal microbiota transplantation, dietary intervention, and probiotic supplementation has become a research hotspot in obesity treatment. In addition, the oral microbiota is also considered closely related to the occurrence and development of obesity due to its regulatory effect on the balance of gut microbiota. Exploring the relationship between oral and gut microbiota and childhood obesity elucidates the pathogenesis and treatment concepts of childhood obesity from a new perspective. It may provide new methods for the prevention and treatment of childhood obesity in the future.}, }
@article {pmid36624625, year = {2023}, author = {Oh, L and Ab Rahman, S and Dubinsky, K and Azanan, MS and Ariffin, H}, title = {Manipulating the Gut Microbiome as a Therapeutic Strategy to Mitigate Late Effects in Childhood Cancer Survivors.}, journal = {Technology in cancer research &amp; treatment}, volume = {22}, number = {}, pages = {15330338221149799}, pmid = {36624625}, issn = {1533-0338}, mesh = {Child ; Adolescent ; Humans ; *Cancer Survivors ; *Gastrointestinal Microbiome ; Dysbiosis/etiology/therapy ; *Neoplasms/therapy ; Disease Progression ; Inflammation ; }, abstract = {Recent studies have identified causal links between altered gut microbiome, chronic inflammation, and inflammation-driven conditions such as diabetes and cardiovascular disease. Childhood cancer survivors (CCS) show late effects of therapy in the form of inflammaging-related disorders as well as microbial dysbiosis, supporting a hypothesis that the conditions are interconnected. Given the susceptibility of the gut microbiome to alteration, a number of therapeutic interventions have been investigated for the treatment of inflammatory conditions, though not within the context of cancer survivorship in children and adolescents. Here, we evaluate the potential for these interventions, which include probiotic supplementation, prebiotics/fiber-rich diet, exercise, and fecal microbiota transplantation for prevention and treatment of cancer treatment-related microbial dysbiosis in survivors. We also make recommendations to improve adherence and encourage long-term lifestyle changes for maintenance of healthy gut microbiome in CCS as a potential strategy to mitigate treatment-related late effects.}, }
@article {pmid36624505, year = {2023}, author = {Green, JE and McGuinness, AJ and Berk, M and Castle, D and Athan, E and Hair, C and Strandwitz, P and Loughman, A and Nierenberg, AA and Cryan, JF and Mohebbi, M and Jacka, F}, title = {Safety and feasibility of faecal microbiota transplant for major depressive disorder: study protocol for a pilot randomised controlled trial.}, journal = {Pilot and feasibility studies}, volume = {9}, number = {1}, pages = {5}, pmid = {36624505}, issn = {2055-5784}, abstract = {BACKGROUND: Mental disorders, including major depressive disorder (MDD), are a leading cause of non-fatal burden of disease globally. Current conventional treatments for depression have significant limitations, and there have been few new treatments in decades. The microbiota-gut-brain-axis is now recognised as playing a role in mental and brain health, and promising preclinical and clinical data suggest Faecal Microbiota Transplants (FMT) may be efficacious for treating a range of mental illnesses. However, there are no existing published studies in humans evaluating the efficacy of FMT for MDD.<br><br>METHODS AND DESIGN: This protocol describes an 8-week, triple-blind, 2:1 parallel group, randomised controlled pilot trial (n = 15), of enema-delivered FMT treatment (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. There will be a further 26-week follow-up to monitor longer-term safety. Participants will receive four FMT or placebo enemas over four consecutive days. The primary aims of the study are to evaluate feasibility and safety of FMT as an adjunctive treatment for MDD in adults. Changes in gut microbiota will be assessed as a secondary outcome. Other data will be collected, including changes in depression and anxiety symptoms, and safety parameters.<br><br>DISCUSSION: Modification of the microbiota-gut-brain axis via FMT is a promising potential treatment for MDD, but there are no published rigorous clinical trials evaluating its use. If this study finds that our FMT strategy is safe and feasible, a larger fully powered RCT is planned. Further high-quality research in this field is urgently needed to address unmet need.<br><br>TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12621000932864.}, }
@article {pmid36623885, year = {2023}, author = {Uehara, S and Higuchi, Y and Yoneda, N and Kato, H and Yamazaki, H and Suemizu, H}, title = {The Unique Human N10-Glucuronidated Metabolite Formation from Olanzapine in Chimeric NOG-TKm30 Mice with Humanized Livers.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {51}, number = {4}, pages = {480-491}, doi = {10.1124/dmd.122.001102}, pmid = {36623885}, issn = {1521-009X}, mesh = {Swine ; Humans ; Mice ; Rats ; Animals ; Rabbits ; Dogs ; Guinea Pigs ; Olanzapine/metabolism ; *Glucuronides/metabolism ; Swine, Miniature/metabolism ; *Microsomes, Liver/metabolism ; Glucuronosyltransferase/metabolism ; UDP-Glucuronosyltransferase 1A9 ; Mice, Inbred Strains ; Liver/metabolism ; }, abstract = {Olanzapine is an antipsychotic agent with species-dependent pharmacokinetic profiles in both humans and animals. In the present study, the metabolic profiles of olanzapine in vitro and in vivo were compared in non-transplanted immunodeficient NOG-TKm30 mice and chimeric mice with humanized livers (hereafter humanized-liver mice). Hepatic microsomal fractions prepared from humanized-liver mice and humans mediated olanzapine N10-glucuronidation, whereas fractions from cynomolgus monkeys, marmosets, minipigs, dogs, rabbits, guinea pigs, rats, CD1 mice, and NOG-TKm30 mice did not. The olanzapine N10-glucuronidation activity in liver microsomes from humanized-liver mice was inhibited by hecogenin, a human UDP-glucuronosyltransferase (UGT) 1A4 inhibitor. In addition, hepatocytes from humanized-liver mice suggest that olanzapine N10-glucuronidation was a major metabolic pathway in the livers of humanized-liver mice. After a single oral dose of olanzapine (10 mg/kg body weight) to humanized-liver mice and control NOG-TKm30 mice, olanzapine N10-glucuronide isomers and olanzapine N4'-glucuronide were detected only in the plasma of humanized-liver mice. In contrast, the area under the curve for N4'-demethylolanzapine, 2-hydroxymethylolanzapine, and 7-hydroxyolanzapine glucuronide was higher in NOG-TKm30 mice than that in humanized-liver mice. The cumulative excreted amounts of olanzapine N10-glucuronide isomers were high in the urine and feces from humanized-liver mice, whereas the cumulative excreted amounts of 2-hydroxymethylolanzapine were higher in NOG-TKm30 mice than in humanized-liver mice. Thus, production of human-specific olanzapine N10-glucuronide was observed in humanized-liver mice, which was consistent with the in vitro glucuronidation data. These results suggest that humanized-liver mice are useful for studying drug oxidation and conjugation of olanzapine in humans. SIGNIFICANCE STATEMENT: Human-specific olanzapine N10-glucuronide isomers were generated in chimeric NOG-TKm30 mice with humanized livers (humanized-liver mice), and high UGT1A4-dependent N10-glucuronidation was observed in the liver microsomes from humanized-liver mice. Hence, humanized-liver mice may be a suitable model for studying UGT1A4-dependent biotransformation of drugs in humans.}, }
@article {pmid36620981, year = {2023}, author = {Baunwall, SMD and Andreasen, SE and Hansen, MM and Kelsen, J and Høyer, KL and Rågård, N and Eriksen, LL and Støy, S and Rubak, T and Damsgaard, EMS and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Faecal microbiota transplantation for first and second episodes of Clostridioides difficile infection - Authors' reply.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {8}, number = {2}, pages = {112-113}, doi = {10.1016/S2468-1253(22)00424-1}, pmid = {36620981}, issn = {2468-1253}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; *Clostridioides difficile ; }, }
@article {pmid36620980, year = {2023}, author = {Krutova, M and Davis, K and Guery, B and Barbut, F}, title = {Faecal microbiota transplantation for first and second episodes of Clostridioides difficile infection.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {8}, number = {2}, pages = {111-112}, doi = {10.1016/S2468-1253(22)00388-0}, pmid = {36620980}, issn = {2468-1253}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; *Clostridioides difficile ; }, }
@article {pmid36620979, year = {2023}, author = {Aby, ES and Rajasingham, R and Enns, EA and Vaughn, BP}, title = {Faecal microbiota transplantation for first and second episodes of Clostridioides difficile infection.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {8}, number = {2}, pages = {110-111}, doi = {10.1016/S2468-1253(22)00353-3}, pmid = {36620979}, issn = {2468-1253}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; *Clostridioides difficile ; }, }
@article {pmid36620978, year = {2023}, author = {Goldenberg, SD and Merrick, B}, title = {Faecal microbiota transplantation for first and second episodes of Clostridioides difficile infection.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {8}, number = {2}, pages = {109-110}, doi = {10.1016/S2468-1253(22)00343-0}, pmid = {36620978}, issn = {2468-1253}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; *Clostridioides difficile ; }, }
@article {pmid36620977, year = {2023}, author = {van Prehn, J and Fitzpatrick, F and Kuijper, EJ and , }, title = {Faecal microbiota transplantation for first and second episodes of Clostridioides difficile infection.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {8}, number = {2}, pages = {109}, doi = {10.1016/S2468-1253(22)00342-9}, pmid = {36620977}, issn = {2468-1253}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; *Clostridioides difficile ; }, }
@article {pmid36620345, year = {2022}, author = {Xiang, H and Liu, QP}, title = {Alterations of the gut microbiota in coronavirus disease 2019 and its therapeutic potential.}, journal = {World journal of gastroenterology}, volume = {28}, number = {47}, pages = {6689-6701}, pmid = {36620345}, issn = {2219-2840}, mesh = {Humans ; *COVID-19/therapy ; SARS-CoV-2 ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology ; *Gastrointestinal Diseases ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global health. SARS-CoV-2 infects host cells primarily by binding to angiotensin-converting enzyme 2, which is coexpressed in alveolar type 2 cells and gut epithelial cells. It is known that COVID-19 often presents with gastrointestinal symptoms and gut dysbiosis, mainly characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria. In recent years, multiple studies have comprehensively explored gut microbiota alterations in COVID-19 and highlighted the clinical correlation between dysbiosis and COVID-19. SARS-CoV-2 causes gastrointestinal infections and dysbiosis mainly through fecal-oral transmission and the circulatory and immune pathways. Studies have shown that the gut microbiota and its metabolites can regulate the immune response and modulate antiviral effects. In addition, the gut microbiota is closely related to gastrointestinal symptoms, such as diarrhea, a common gastrointestinal symptom among COVID-19. Therefore, the contribution of the gut microbiota in COVID-19 should not be overlooked. Strategies targeting the gut microbiota via probiotics, prebiotics and fecal microbiota transplantation should be considered to treat this patient population in the future. However, the specific alterations and mechanisms as well as the contributions of gut microbiota in COVID-19 should be urgently further explored.}, }
@article {pmid36620003, year = {2022}, author = {Zhang, L and Lang, H and Ran, L and Tian, G and Shen, H and Zhu, J and Zhang, Q and Yi, L and Mi, M}, title = {Long-term high loading intensity of aerobic exercise improves skeletal muscle performance via the gut microbiota-testosterone axis.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1049469}, pmid = {36620003}, issn = {1664-302X}, abstract = {Exercise is reported to play a crucial role in skeletal muscle performance. However, the underlying mechanism is still unknown. Thus, we investigated the effect of high-intensity aerobic exercise on skeletal muscle performance. In this study, the male C57BL/6J mice were accepted by high-intensity aerobic exercise for 8 weeks to establish an exercise model. It was observed that high-intensity aerobic exercise markedly affected the expression of genes in skeletal muscle. Moreover, high-intensity aerobic exercise significantly improved skeletal muscle grip strength and serum testosterone levels. HE staining showed that the cross-sectional area (CSA) of the skeletal muscle was successfully increased after 8 weeks of high-intensity aerobic exercise. Additionally, we found that high-intensity aerobic exercise changed gut microbiota structure by altering the abundance of Akkermansia, Allobaculum, and Lactobacillus, which might be related to testosterone production. However, the beneficial effects disappeared after the elimination of the gut microbiota and recovered after fecal microbiota transplantation (FMT) experiments for 1 week. These results indicated that the beneficial effects of high-intensity aerobic exercise on skeletal muscle were partly dependent on the gut microbiota. Our results suggested that long-term high loading intensity of aerobic exercise could improve skeletal muscle performance, which was probably due to the gut microbiota-testosterone axis.}, }
@article {pmid36618438, year = {2022}, author = {Ramos, RJ and Zhu, C and Joseph, DF and Thaker, S and Lacomb, JF and Markarian, K and Lee, HJ and Petrov, JC and Monzur, F and Buscaglia, JM and Chawla, A and Small-Harary, L and Gathungu, G and Morganstern, JA and Yang, J and Li, J and Pamer, EG and Robertson, CE and Frank, DN and Cross, JR and Li, E}, title = {Metagenomic and bile acid metabolomic analysis of fecal microbiota transplantation for recurrent Clostridiodes difficile and/or inflammatory bowel diseases.}, journal = {Medical research archives}, volume = {10}, number = {10}, pages = {}, pmid = {36618438}, issn = {2375-1916}, support = {R25 AI140472/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infections (rCDI), but has more limited efficacy in treating either ulcerative colitis (UC) or Crohn's disease (CD), two major forms of inflammatory bowel diseases (IBD). We hypothesize that FMT recipients with rCDI and/or IBD have baseline fecal bile acid (BA) compositions that differ significantly from that of their healthy donors and that FMT will normalize the BA compositions.<br><br>AIM: To study the effect of single colonoscopic FMT on microbial composition and function in four recipient groups: 1.) rCDI patients without IBD (rCDI-IBD); 2.) rCDI with IBD (rCDI+IBD); 3.) UC patients without rCDI (UC-rCDI); 4.) CD patients without rCDI (CD-rCDI).<br><br>METHODS: We performed 16S rRNA gene sequence, shotgun DNA sequence and quantitative bile acid metabolomic analyses on stools collected from 55 pairs of subjects and donors enrolled in two prospective single arm FMT clinical trials (Clinical Trials.gov ID NCT03268213, 479696, UC no rCDI &#x2265; 2x IND 1564 and NCT03267238, IND 16795). Fitted linear mixed models were used to examine the effects of four recipient groups, FMT status (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on microbial diversity and composition, bile acid metabolites and bile acid metabolizing enzyme gene abundance.<br><br>RESULTS: The pre-FMT stools collected from rCDI &#xb1; IBD recipients had reduced &#x3b1;-diversity compared to the healthy donor stools and was restored post-FMT. The &#x3b1;-diversity in the pre-FMT stools collected from UC-rCDI or CD-rCDI recipients did not differ significantly from donor stools. FMT normalized some recipient/donor ratios of genus level taxa abundance in the four groups. Fecal secondary BA levels, including some of the secondary BA epimers that exhibit in vitro immunomodulatory activities, were lower in rCDI&#xb1;IBD and CD-rCDI but not UC-rCDI recipients compared to donors. FMT restored secondary BA levels. Metagenomic baiE gene and some of the eight bile salt hydrolase (BSH) phylotype abundances were significantly correlated with fecal BA levels.<br><br>CONCLUSION: Restoration of multiple secondary BA levels, including BA epimers implicated in immunoregulation, are associated with restoration of fecal baiE gene counts, suggesting that the 7-&#x3b1;-dehydroxylation step is rate-limiting.}, }
@article {pmid36615885, year = {2023}, author = {Flaig, B and Garza, R and Singh, B and Hamamah, S and Covasa, M}, title = {Treatment of Dyslipidemia through Targeted Therapy of Gut Microbiota.}, journal = {Nutrients}, volume = {15}, number = {1}, pages = {}, pmid = {36615885}, issn = {2072-6643}, mesh = {*Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics ; *Synbiotics ; *Microbiota ; }, abstract = {Dyslipidemia is a multifaceted condition with various genetic and environmental factors contributing to its pathogenesis. Further, this condition represents an important risk factor for its related sequalae including cardiovascular diseases (CVD) such as coronary artery disease (CAD) and stroke. Emerging evidence has shown that gut microbiota and their metabolites can worsen or protect against the development of dyslipidemia. Although there are currently numerous treatment modalities available including lifestyle modification and pharmacologic interventions, there has been promising research on dyslipidemia that involves the benefits of modulating gut microbiota in treating alterations in lipid metabolism. In this review, we examine the relationship between gut microbiota and dyslipidemia, the impact of gut microbiota metabolites on the development of dyslipidemia, and the current research on dietary interventions, prebiotics, probiotics, synbiotics and microbiota transplant as therapeutic modalities in prevention of cardiovascular disease. Overall, understanding the mechanisms by which gut microbiota and their metabolites affect dyslipidemia progression will help develop more precise therapeutic targets to optimize lipid metabolism.}, }
@article {pmid36615662, year = {2022}, author = {Zhang, W and Zhang, Y and Li, Y and Ma, D and Zhang, H and Kwok, LY}, title = {Lacticaseibacillus rhamnosus Probio-M9-Driven Mouse Mammary Tumor-Inhibitory Effect Is Accompanied by Modulation of Host Gut Microbiota, Immunity, and Serum Metabolome.}, journal = {Nutrients}, volume = {15}, number = {1}, pages = {}, pmid = {36615662}, issn = {2072-6643}, support = {31972083//National Natural Science Foundation of China/ ; 2021ZD0014//Science and Technology Major Projects of Inner Mongolia Autonomous Region/ ; }, mesh = {Female ; Mice ; Animals ; *Lacticaseibacillus rhamnosus ; *Gastrointestinal Microbiome/physiology ; Lacticaseibacillus ; Pilot Projects ; *Microbiota ; *Probiotics ; }, abstract = {Gut microbiome may influence tumor growth and cancer treatment efficacy, so it is a potential target for tumor prevention/treatment. This pilot study investigated the preventive and therapeutic effects of a probiotic strain, Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9), against murine mammary cancer. Thirty-six female mice were randomly divided into three groups (n = 12 per group): control (without tumor transplantation), model (tumor transplantation; no probiotic administration), and probiotic (30-day oral gavage of probiotic, started seven days before tumor transplantation). Changes in tumor size were recorded, and blood, tumor tissue, and stool samples were collected at the end of the trial for analyses. Comparing with the model group, the probiotic group had a significantly smaller tumor volume (p < 0.05), a higher fecal microbiota Shannon diversity index, with significant modifications in the gut microbiota structure (p < 0.05), characterized by more Alistipes sp._2, Porphyromonadaceae bacterium_7, and Bacteroidales bacterium 55_9 (p < 0.05). Additionally, Probio-M9 administration elevated the serum IFN-γ, IL-9, IL-13, and IL-27 levels and several metabolites (e.g., pyridoxal, nicotinic acid, 3-hydroxybutyric acid, glutamine; p < 0.05), while reducing IL-5 (p < 0.05). These changes might be associated with the protective effect of Probio-M9 against mammary tumor growth. Thus, probiotic administration could harness host gut microbiome in anti-cancer responses.}, }
@article {pmid36611911, year = {2022}, author = {Elangovan, S and Borody, TJ and Holsinger, RMD}, title = {Fecal Microbiota Transplantation Reduces Pathology and Improves Cognition in a Mouse Model of Alzheimer's Disease.}, journal = {Cells}, volume = {12}, number = {1}, pages = {}, pmid = {36611911}, issn = {2073-4409}, mesh = {Humans ; Mice ; Animals ; Fecal Microbiota Transplantation ; *Alzheimer Disease/therapy ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Disease Models, Animal ; Cognition ; }, abstract = {Characterized by the presence of amyloid plaques, neurofibrillary tangles and neuroinflammation, Alzheimer's disease (AD) is a progressive neurodegenerative disorder with no known treatment or cure. Global disease projections warrant an urgent and rapid therapeutic for the treatment of this devastating disease. Fecal microbiota transplantation (FMT) is a widely accepted and safely used treatment for recurrent Clostridium difficile infection and other metabolic diseases such as diabetes mellitus. FMT has also been demonstrated to be a possible AD therapeutic. We examined the potential of FMT for the treatment of AD in a robust, mouse model of the disease and report that a brief, 7-day treatment regimen demonstrated 'plaque-busting' and behavior-modifying effects in treated 5xFAD mice. Importantly, we show that donor age plays an important role in the efficacy of the treatment and these findings warrant further investigation in human trials.}, }
@article {pmid36611848, year = {2022}, author = {Anand, N and Gorantla, VR and Chidambaram, SB}, title = {The Role of Gut Dysbiosis in the Pathophysiology of Neuropsychiatric Disorders.}, journal = {Cells}, volume = {12}, number = {1}, pages = {}, pmid = {36611848}, issn = {2073-4409}, mesh = {Humans ; *Dysbiosis ; Ecosystem ; Brain ; *Gastrointestinal Microbiome/physiology ; Anxiety ; }, abstract = {Mounting evidence shows that the complex gut microbial ecosystem in the human gastrointestinal (GI) tract regulates the physiology of the central nervous system (CNS) via microbiota and the gut-brain (MGB) axis. The GI microbial ecosystem communicates with the brain through the neuroendocrine, immune, and autonomic nervous systems. Recent studies have bolstered the involvement of dysfunctional MGB axis signaling in the pathophysiology of several neurodegenerative, neurodevelopmental, and neuropsychiatric disorders (NPDs). Several investigations on the dynamic microbial system and genetic-environmental interactions with the gut microbiota (GM) have shown that changes in the composition, diversity and/or functions of gut microbes (termed "gut dysbiosis" (GD)) affect neuropsychiatric health by inducing alterations in the signaling pathways of the MGB axis. Interestingly, both preclinical and clinical evidence shows a positive correlation between GD and the pathogenesis and progression of NPDs. Long-term GD leads to overstimulation of hypothalamic-pituitary-adrenal (HPA) axis and the neuroimmune system, along with altered neurotransmitter levels, resulting in dysfunctional signal transduction, inflammation, increased oxidative stress (OS), mitochondrial dysfunction, and neuronal death. Further studies on the MGB axis have highlighted the significance of GM in the development of brain regions specific to stress-related behaviors, including depression and anxiety, and the immune system in the early life. GD-mediated deregulation of the MGB axis imbalances host homeostasis significantly by disrupting the integrity of the intestinal and blood-brain barrier (BBB), mucus secretion, and gut immune and brain immune functions. This review collates evidence on the potential interaction between GD and NPDs from preclinical and clinical data. Additionally, we summarize the use of non-therapeutic modulators such as pro-, pre-, syn- and post-biotics, and specific diets or fecal microbiota transplantation (FMT), which are promising targets for the management of NPDs.}, }
@article {pmid36610712, year = {2023}, author = {}, title = {Corrigendum to: Efficacy and Outcomes of Faecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease.}, journal = {Journal of Crohn's &amp; colitis}, volume = {17}, number = {5}, pages = {823}, doi = {10.1093/ecco-jcc/jjac195}, pmid = {36610712}, issn = {1876-4479}, }
@article {pmid36610264, year = {2023}, author = {Zheng, M and Zhou, W and Huang, C and Hu, Z and Zhang, B and Lu, Q and Zhao, M}, title = {A single-cell map of peripheral alterations after FMT treatment in patients with systemic lupus erythematosus.}, journal = {Journal of autoimmunity}, volume = {135}, number = {}, pages = {102989}, doi = {10.1016/j.jaut.2022.102989}, pmid = {36610264}, issn = {1095-9157}, mesh = {Humans ; *CD8-Positive T-Lymphocytes ; Fecal Microbiota Transplantation ; Lymphocytes ; Interferons ; *Lupus Erythematosus, Systemic ; }, abstract = {Systemic lupus erythematosus (SLE) is characterized by loss of self-tolerance and persistent self-aggression, sustained chronic inflammation, production of autoantibodies and multi-system damage, and is largely incurable to date. The gut microbiota and its metabolites, now recognized as crucial environmental triggers of local/systemic immune reactions, have been implicated in the development and progression of SLE. Fecal microbiota transplantation (FMT) is restoration of disturbed microbiota by transplanting foreign gut microbiota from healthy individuals into the gastrointestinal tract of diseased individuals. Our previous clinical trial suggests that FMT is a potentially safe and effective treatment for SLE. In order to elucidate the potential effect of FMT on peripheral immune cells of patients with SLE, we collected PBMCs (n = 30) of 13 SLE patients who participated in the clinical trial before and after the FMT-treatment, and performed single-cell RNA sequencing. The results first revealed that peripheral T lymphocytes of SLE patients decreased and NK cells increased after the FMT treatment. Then, sub-clustering analysis discovered that total CD4[+] T cells highly expressed genes of IL7R, CD28, and CD8[+] T cells highly expressed genes of GZMH and NKG7 after FMT treatment. Moreover, FMT treatment reduced the expression of interferon-related genes (IRGs) in CD4[+] T, CD8[+] T, DP, NK, and B cells of SLE patients. More importantly, interferon-related pathways were more enriched in cells of the FMT non-responder group, and further the interferon genes expression of lymphocytes and myeloid cells was negatively correlated with the efficiency of FMT treatment. Collectively, our data identified various immunophenotypic and associated gene set changes following FMT treatment, illustrating the heterogeneity of response to FMT treatment in SLE.}, }
@article {pmid36610135, year = {2023}, author = {Luo, Z and Xu, W and Yuan, T and Shi, C and Jin, T and Chong, Y and Ji, J and Lin, L and Xu, J and Zhang, Y and Kang, A and Zhou, W and Xie, T and Di, L and Shan, J}, title = {Platycodon grandiflorus root extract activates hepatic PI3K/PIP3/Akt insulin signaling by enriching gut Akkermansia muciniphila in high fat diet fed mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {109}, number = {}, pages = {154595}, doi = {10.1016/j.phymed.2022.154595}, pmid = {36610135}, issn = {1618-095X}, mesh = {Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; Insulin/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; *Insulin Resistance ; Diet, High-Fat/adverse effects ; Mice ; Animals ; Mice, Inbred C57BL ; *Platycodon ; Akkermansia ; *Metabolic Syndrome ; Plant Extracts/pharmacology ; }, abstract = {BACKGROUND: Increasing hepatic insulin signaling is found to be an important mechanism of Platycodon grandiflorus root to alleviate metabolic syndrome (MetS) symptoms such as insulin resistance, obesity, hyperlipidemia and hepatic steatosis, but the details are not yet clear. Since the main constituents of Platycodon grandiflorus root were hard to be absorbed by gastrointestinal tract, getting opportunity to interact with gut microbiota, we speculate the gut microorganisms may mediate its effect.<br><br>PURPOSE: Our work aimed to confirm the critical role of gut microbes in the intervention of Platycodon grandiflorus root extract (PRE) on MetS, and investigate the mechanism.<br><br>METHODS: Biochemical analyses, glucose tolerance test and hepatic lipidomics analysis were used to evaluate the anti-MetS effect of PRE on high fat diet (HFD) fed mice. Perform 16S rDNA analysis, qPCR analysis and in vitro co-incubation experiment to study its effect on gut microbes, followed by fecal microbiota transplantation (FMT) experiment and antibiotics intervention experiment. Also, the effect of Akkermansia muciniphila treatment on HFD mice was investigated.<br><br>RESULTS: PRE alleviated lipid accumulation and insulin resistance in HFD mice and remodeled the fecal microbiome. It also increased the gene expression of colonic tight junction proteins, alleviated metabolic endotoxemia and inflammation, so that reduced TNF-&#x3b1; induced hepatic JNK-dependent IRS-1 serine phosphorylation and the impairment of PI3K/PIP3/Akt insulin signaling pathway. A. muciniphila was one of the most significantly enriched microbes by PRE treatment, and its administration to HFD mice showed similar effects to PRE, repairing the gut barrier and activating hepatic PI3K/PIP3/Akt pathway. Finally, anti-MetS effect of PRE could be delivered to FMT recipients, and PRE could not further attenuate MetS in gut microbiota depleted mice.<br><br>CONCLUSION: We demonstrated for the first time that PRE alleviated MetS in a gut microbiota dependent manner, and found activation of hepatic insulin signaling mediated by gut A. muciniphila was a potential mechanism of it.}, }
@article {pmid36608164, year = {2023}, author = {Li, J and Liu, H and Guo, F and Guo, R and Zhang, H and He, X and Ming, X and Ma, X and Shang, G and Ji, P and Song, L and Gao, S}, title = {Increased GABAergic projections in the paraventricular nucleus regulate colonic hypersensitivity via oxytocin in a rat model of irritable bowel syndrome.}, journal = {Neuroreport}, volume = {34}, number = {2}, pages = {108-115}, doi = {10.1097/WNR.0000000000001867}, pmid = {36608164}, issn = {1473-558X}, mesh = {Rats ; Animals ; *Irritable Bowel Syndrome/drug therapy ; Paraventricular Hypothalamic Nucleus/metabolism ; Oxytocin ; Hyperalgesia ; Feces ; }, abstract = {Irritable bowel syndrome (IBS) is characterized by gastrointestinal dysmotility and visceral hyperalgesia, and the impaired brain-gut axis is accepted as a crucial cause for the onset of IBS. The objective of this study is to investigate the effects of the adaptive changes in the central neural system induced by stress on IBS-like syndromes in rats. Long-term water avoidance stress (WAS) was used to prepare IBS animals. The changes in neuronal excitation and GABA expression were shown by immunohistochemistry. The mRNA and protein expressions of neurotransmitters were detected with Quantitative reverse-transcription PCR (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA). The intestinal transit time, fecal moisture content, and abdominal withdrawal reflex scores of rats were recorded to monitor intestinal motility and visceral hyperalgesia. In the WAS-treated rats with enhanced intestinal motility and visceral hypersensitivity, more GABAergic projections were found in the paraventricular nucleus (PVN) of the hypothalamus, which inhibited the firing rate of neurons and decreased the expression of oxytocin. Exogenous oxytocin improved gut motility and decreased AWR scores. The inhibition of oxytocin by the adaptive GABAergic projection in the PVN might be an important mediator of IBS, which indicates a potential novel therapeutic target.}, }
@article {pmid36605728, year = {2022}, author = {Gangadhar, M and Kottapalli, A and Kottapalli, V}, title = {A Novel Treatment Approach to Treatment-Resistant, Recurrent Clostridium difficile.}, journal = {Case reports in gastroenterology}, volume = {16}, number = {3}, pages = {646-651}, pmid = {36605728}, issn = {1662-0631}, abstract = {A 36-year-old male with a previous medical history of persistent Clostridium difficile presented to clinic for evaluation of diarrheal symptoms intermittently for the last 2 years. He reported recurrent episodes of C. difficile that initially began after prophylactic antibiotic use prior to a tooth extraction. He underwent 12 unsuccessful treatment trials at a nearby clinic with courses of vancomycin, metronidazole, and fidaxomicin. His chronic diarrhea had caused him to endure significant lifestyle alterations over the years. After multiple episodes of incomplete bacterial clearance, he was referred to a university-based tertiary care facility but instead opted for care at a nearby clinic. Upon work-up, his serology was again positive for C. difficile, and he was initiated on a 14-day course of fidaxomicin 200 mg p.o. BID, along with yogurt and probiotic supplementation. Despite fidaxomicin treatment, subsequent serological PCR testing for C. difficile remained positive, consistent with CT abdomen and pelvis findings suspicious for enteritis. His recurrent resistance to standard therapy protocols inspired an unconventional treatment approach: another 14-day course of fidaxomicin 200 mg p.o. BID, followed by fidaxomicin 200 mg p.o. each morning and cholestyramine 4 g p.o. each evening for another 2 weeks, concluded by fecal microbial transplant. Two weeks following this antibiotic regimen and fecal transplant, serology was negative for C. difficile. Subsequent follow-up revealed no evidence of recurrence.}, }
@article {pmid36605506, year = {2022}, author = {Zhang, W and Xie, J and Xia, S and Fan, X and Schmitz-Esser, S and Zeng, B and Zheng, L and Huang, H and Wang, H and Zhong, J and Zhang, Z and Zhang, L and Jiang, M and Hou, R}, title = {Evaluating a potential model to analyze the function of the gut microbiota of the giant panda.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1086058}, pmid = {36605506}, issn = {1664-302X}, abstract = {To contribute to the conservation of endangered animals, the utilization of model systems is critical to analyze the function of their gut microbiota. In this study, the results of a fecal microbial transplantation (FMT) experiment with germ-free (GF) mice receiving giant panda or horse fecal microbiota showed a clear clustering by donor microbial communities in GF mice, which was consistent with the results of blood metabolites from these mice. At the genus level, FMT re-established approximately 9% of the giant panda donor microbiota in GF mice compared to about 32% for the horse donor microbiota. In line with this, the difference between the panda donor microbiota and panda-mice microbiota on whole-community level was significantly larger than that between the horse donor microbiota and the horse-mice microbiota. These results were consistent with source tracking analysis that found a significantly higher retention rate of the horse donor microbiota (30.9%) than the giant panda donor microbiota (4.0%) in GF mice where the microbiota remained stable after FMT. Further analyzes indicated that the possible reason for the low retention rate of the panda donor microbiota in GF mice was a low relative abundance of Clostridiaceae in the panda donor microbiota. Our results indicate that the donor microbiota has a large effect on GF mice microbiota after FMT.}, }
@article {pmid36604442, year = {2023}, author = {Le Guern, R and Grandjean, T and Stabler, S and Bauduin, M and Gosset, P and Kipnis, &#xc9; and Dessein, R}, title = {Gut colonisation with multidrug-resistant Klebsiella pneumoniae worsens Pseudomonas aeruginosa lung infection.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {78}, pmid = {36604442}, issn = {2041-1723}, mesh = {Animals ; Mice ; Male ; *Pseudomonas aeruginosa ; Klebsiella pneumoniae ; Dysbiosis ; Mice, Inbred C57BL ; Lung ; *Pseudomonas Infections ; Fatty Acids, Volatile ; }, abstract = {Carbapenemase-producing Enterobacterales (CPE) are spreading rapidly in hospital settings. Asymptomatic CPE gut colonisation may be associated with dysbiosis and gut-lung axis alterations, which could impact lung infection outcomes. In this study, in male C57BL/6JRj mice colonised by CPE, we characterise the resulting gut dysbiosis, and analyse the lung immune responses and outcomes of subsequent Pseudomonas aeruginosa lung infection. Asymptomatic gut colonisation by CPE leads to a specific gut dysbiosis and increases the severity of P. aeruginosa lung infection through lower numbers of alveolar macrophages and conventional dendritic cells. CPE-associated dysbiosis is characterised by a near disappearance of the Muribaculaceae family and lower levels of short-chain fatty acids. Faecal microbiota transplantation restores immune responses and outcomes of lung infection outcomes, demonstrating the involvement of CPE colonisation-induced gut dysbiosis in altering the immune gut-lung axis, possibly mediated by microbial metabolites such as short-chain fatty acids.}, }
@article {pmid36604080, year = {2023}, author = {Liu, Y and Li, P and Pan, W and Zhao, J and Olnood, CG and Liu, Y and Xu, YJ}, title = {Salecan confers anti-inflammatory effects in liver injury via regulating gut microbiota and its metabolites.}, journal = {Carbohydrate polymers}, volume = {302}, number = {}, pages = {120418}, doi = {10.1016/j.carbpol.2022.120418}, pmid = {36604080}, issn = {1879-1344}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Liver ; *beta-Glucans/pharmacology ; Anti-Inflammatory Agents/pharmacology/therapeutic use/metabolism ; Mice, Inbred C57BL ; }, abstract = {Salecan, a natural β-glucan and one of the novel food ingredients approved in China, has been shown a variety of positive health effects, yet the mechanism of liver injury remains poorly understood. In addition, β-glucan could induce the shifts in gut microbiota, however, whether modulation of gut microbiota by β-glucan is associated with their positive health effects remain elusive. Here, the anti-inflammatory effects and the underlying mechanism of Salecan supplementation in CCl4-induced liver injury were investigated. After 8 weeks of treatment, we observed that Salecan alleviated liver injury by regulating inflammatory response and M2 macrophage polarization. In addition, Salecan treatment modulated the composition of gut microbiota and antibiotic cocktail treatment indicated that the hepatoprotective effect of Salecan was dependent on the gut microbiota. Fecal microbiota transplantation was used to further verify the mechanism, and we confirmed that microbial colonization partially alleviated liver injury. Besides, microbiota-derived metabolites of Salecan also contributed to the hepatoprotective and anti-inflammatory effect of Salecan against liver injury. These findings supported that Salecan intervention attenuated liver injury by regulating gut microbiota and its metabolites.}, }
@article {pmid36601003, year = {2022}, author = {Shang, J and Cui, W and Guo, R and Zhang, Y and Wang, P and Yu, W and Zheng, X and Wang, T and Dong, Y and Zhao, J and Ding, S and Xiao, J and Ren, Z and Zhao, Z}, title = {The harmful intestinal microbial community accumulates during DKD exacerbation and microbiome-metabolome combined validation in a mouse model.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {964389}, pmid = {36601003}, issn = {1664-2392}, mesh = {Humans ; Mice ; Animals ; RNA, Ribosomal, 16S/genetics/analysis ; *Metabolome ; *Microbiota ; Feces ; Disease Models, Animal ; }, abstract = {OBJECTIVE: Diabetic kidney disease (DKD) is one of the most prevalent complications of diabetes mellitus (DM) and is associated with gut microbial dysbiosis. We aim to build a diagnostic model to aid clinical practice and uncover a crucial harmful microbial community that contributes to DKD pathogenesis and exacerbation.<br><br>DESIGN: A total of 528 fecal samples from 180 DKD patients and 348 non-DKD populations (138 DM and 210 healthy volunteers) from the First Affiliated Hospital of Zhengzhou University were recruited and randomly divided into a discovery phase and a validation phase. The gut microbial composition was compared using 16S rRNA sequencing. Then, the 180 DKD patients were stratified into four groups based on clinical stages and underwent gut microbiota analysis. We established DKD mouse models and a healthy fecal microbiota transplantation (FMT) model to validate the effects of gut microbiota on DKD and select the potential harmful microbial community. Untargeted metabolome-microbiome combined analysis of mouse models helps decipher the pathogenetic mechanism from a metabolic perspective.<br><br>RESULTS: The diversity of the gut microbiome was significantly decreased in DKD patients when compared with that of the non-DKD population and was increased in the patients with more advanced DKD stages. The DKD severity in mice was relieved after healthy gut microbiota reconstruction. The common harmful microbial community was accumulated in the subjects with more severe DKD phenotypes (i.e., DKD and DKD5 patients and DKD mice). The harmful microbial community was positively associated with the serum injurious metabolites (e.g., cholic acid and hippuric acid).<br><br>CONCLUSION: The fecal microbial community was altered markedly in DKD. Combining the fecal analysis of both human and animal models selected the accumulated harmful pathogens. Partially recovering healthy gut microbiota can relieve DKD phenotypes via influencing pathogens' effect on DKD mice's metabolism.}, }
@article {pmid36600789, year = {2022}, author = {Perez Del Nogal, G and Patel, N}, title = {Refractory Checkpoint Inhibitor Colitis Responsive to Ustekinumab.}, journal = {ACG case reports journal}, volume = {9}, number = {12}, pages = {e00946}, pmid = {36600789}, issn = {2326-3253}, abstract = {Immune checkpoint inhibitors have transformed the treatment of cancer. Nonetheless, multiple immune-related adverse events have been reported, including checkpoint inhibitor colitis. Severe colitis can be complicated by ileus, megacolon, intestinal perforation, and death. Current appropriate treatment includes steroids, followed by antitumor necrosis factor biologic therapy, infliximab. Alternatively, vedolizumab and fecal microbiota transplantation have reported efficacy for refractory cases. In this study, we present the first case report of a patient with steroid-refractory checkpoint inhibitor-induced colitis due to pembrolizumab for Stage IV anaplastic thyroid carcinoma successfully treated with ustekinumab after failure of infliximab, vedolizumab, and fecal microbiota transplantation. This may lead to a better understanding of treatment options for refractory checkpoint inhibitor colitis.}, }
@article {pmid36600636, year = {2023}, author = {Yao, B and Cai, Y and Wang, W and Deng, J and Zhao, L and Han, Z and Wan, L}, title = {The Effect of Gut Microbiota on the Progression of Intervertebral Disc Degeneration.}, journal = {Orthopaedic surgery}, volume = {15}, number = {3}, pages = {858-867}, pmid = {36600636}, issn = {1757-7861}, support = {202204074627//General items of Hunan Provincial Health Commission/ ; 2019-57//Hunan Health Commission's 2019 Medical Service and Support Capability Improvement Subsidy Fund/ ; }, mesh = {Animals ; Male ; Rats ; Aggrecans ; Collagen/genetics ; *Gastrointestinal Microbiome/genetics ; Interleukin-6 ; *Intervertebral Disc/metabolism ; *Intervertebral Disc Degeneration/microbiology/pathology ; Matrix Metalloproteinase 13/genetics ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; }, abstract = {OBJECTIVE: Intervertebral disc degeneration (IDD) is the main cause of back pain, and its treatment is a serious socio-economic burden. The safety and treatment of fecal microbiota transplantation (FMT) has been established. However, the relationship between FMT and IDD still unclear. We aimed to explore whether FMT plays a role in IDD to provide a reference for the treatment of IDD.<br><br>METHODS: An experimental model of IDD was established using 2-month-old male Sprague-Dawley rats. FMT was performed by intragastric gavage of IDD rats with a fecal bacterial solution. Rat serum, feces, and vertebral disc tissue were collected after surgery for 2 months. The levels of TNF-&#x3b1;, IL-1&#x3b2;, IL-6, matrix metalloproteinase (MMP)-3, MMP-13, Collagen II, and aggrecan in the serum or vertebral disc tissue were measured by an enzyme-linked immunosorbent assay, immunohistochemistry, quantitative real-time polymerase chain reaction, or western blotting. We also examined the pathology of the vertebral disc tissue using hematoxylin and eosin (HE) and safranin O-fast green staining. Finally, we examined the gut microbiota in rat feces using 16&#x2009;S rRNA gene sequencing.<br><br>RESULTS: We found that the expression of TNF-&#x3b1;, IL-1&#x3b2;, IL-6, MMP-3, MMP-13, NLRP3 and Caspase-1 increased in the IDD group rats. In contrast, Collagen II and aggrecan levels were downregulated. Additionally, vertebral disc tissue was severely damaged in the IDD group, with disordered cell arrangement and uneven safranin coloration. FMT reversed the effects of IDD modeling on these factors and alleviated cartilage tissue damage. In addition, FMT increased the gut microbiota diversity and microbial abundance in rats treated with IDD.<br><br>CONCLUSION: Our findings suggest that FMT has a positive effect in maintaining cellular stability in the vertebral disc and alleviating histopathological damage. It affects the diversity and abundance of gut microbiota in rats with IDD. Therefore, FMT may serve as a promising target for amelioration of IDD.}, }
@article {pmid36597735, year = {2023}, author = {Liu, JY and Zhu, YP and Han, BM and Xia, SJ}, title = {[Effects of androgen deprivation therapy for prostate cancer on gut microbiota and treatment].}, journal = {Zhonghua yi xue za zhi}, volume = {103}, number = {2}, pages = {84-88}, doi = {10.3760/cma.j.cn112137-20220822-01789}, pmid = {36597735}, issn = {0376-2491}, mesh = {Male ; Humans ; *Prostatic Neoplasms, Castration-Resistant/drug therapy/metabolism ; Androgens/physiology/therapeutic use ; Androgen Antagonists/therapeutic use ; *Gastrointestinal Microbiome ; Receptors, Androgen/therapeutic use ; }, abstract = {Androgen deprivation therapy is widely regarded as the first-line therapy for advanced prostate cancer. Although the initial efficacy is significant, clinical complications that arise after the therapy can reduce the patient's life quality, affect the efficacy, and even endanger their health or life due to the progression to castration-resistant prostate cancer (CRPC). The gut microbiota is associated not only with local diseases of the intestinal tract but also with systemic diseases such as liver or neurological diseases, but its relationship with prostate cancer is less frequently studied. Androgen deprivation therapy for prostate cancer affects the gut microbiota of prostate cancer patients, thereby inducing relevant complications and promoting CRPC formation. In this review, we present the microecological effects of androgen deprivation therapy for prostate cancer on gut microbiota from the perspectives of gut microbiota diversity, intestinal microbiota structure, and functional pathways. We also propose corresponding countermeasures, such as fecal microbiota transplantation, oral antibiotics, and oral probiotics, to improve the efficacy and outcome of androgen deprivation therapy for prostate cancer by regulating gut microbiota, and provide new ideas for the diagnosis and treatment of advanced prostate cancer.}, }
@article {pmid36596826, year = {2023}, author = {Xu, TT and Chen, P and Zhang, CD and Shaukat, A and Lin, LX and Yue, K and Ding, WL and Tong, X and Liu, KL and He, YF and Xie, JF and Liu, F and Zhang, C and Zhang, HY and Huang, SC}, title = {Gut microbiome dysregulation drives bone damage in broiler tibial dyschondroplasia by disrupting glucose homeostasis.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {1}, pmid = {36596826}, issn = {2055-5008}, mesh = {Animals ; *Osteochondrodysplasias/therapy/veterinary/metabolism ; Thiram ; *Gastrointestinal Microbiome ; Chickens ; RNA, Ribosomal, 16S ; Homeostasis ; Glucose ; }, abstract = {Tibial dyschondroplasia (TD) with multiple incentives is a metabolic skeletal disease that occurs in fast-growing broilers. Perturbations in the gut microbiota (GM) have been shown to affect bone homoeostasis, but the mechanisms by which GM modulates bone metabolism in TD broilers remain unknown. Here, using a broiler model of TD, we noted elevated blood glucose (GLU) levels in TD broilers, accompanied by alterations in the pancreatic structure and secretory function and damaged intestinal barrier function. Importantly, faecal microbiota transplantation (FMT) of gut microbes from normal donors rehabilitated the GM and decreased the elevated GLU levels in TD broilers. A high GLU level is a predisposing factor to bone disease, suggesting that GM dysbiosis-mediated hyperglycaemia might be involved in bone regulation. 16S rRNA gene sequencing and short-chain fatty acid analysis revealed that the significantly increased level of the metabolite butyric acid derived from the genera Blautia and Coprococcus regulated GLU levels in TD broilers by binding to GPR109A in the pancreas. Tibial studies showed reduced expression of vascular regulatory factors (including PI3K, AKT and VEFGA) based on transcriptomics analysis and reduced vascular distribution, contributing to nonvascularization of cartilage in the proximal tibial growth plate of TD broilers with elevated GLU levels. Additionally, treatment with the total flavonoids from Rhizoma drynariae further validated the improvement in bone homoeostasis in TD broilers by regulating GLU levels through the regulation of GM to subsequently improve intestinal and pancreatic function. These findings clarify the critical role of GM-mediated changes in GLU levels via the gut-pancreas axis in bone homoeostasis in TD chickens.}, }
@article {pmid36596758, year = {2023}, author = {Shin, J}, title = {Fecal microbiota transplantation is not a magical treatment, but better too early than too late.}, journal = {The Korean journal of internal medicine}, volume = {38}, number = {1}, pages = {3-4}, pmid = {36596758}, issn = {2005-6648}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; Feces ; *Gastrointestinal Microbiome ; Republic of Korea ; }, }
@article {pmid36596411, year = {2023}, author = {John Kenneth, M and Tsai, HC and Fang, CY and Hussain, B and Chiu, YC and Hsu, BM}, title = {Diet-mediated gut microbial community modulation and signature metabolites as potential biomarkers for early diagnosis, prognosis, prevention and stage-specific treatment of colorectal cancer.}, journal = {Journal of advanced research}, volume = {52}, number = {}, pages = {45-57}, pmid = {36596411}, issn = {2090-1224}, mesh = {Young Adult ; Humans ; *Colorectal Neoplasms/diagnosis/prevention &amp; control ; Dysbiosis/microbiology ; *Microbiota ; Prognosis ; Biomarkers ; Bacteria ; Early Diagnosis ; Diet ; }, abstract = {BACKGROUND: Over the last decade, studies have shown an increased incidence of colorectal cancer (CRC), particularly early onset colorectal cancer (EOCRC). Researchers have demonstrated that dietary behavior, especially among young adults, influences alterations in the gut microbial community, leading to an increased accumulation of pathogenic gut microbiota and a decrease in beneficial ones. Unfortunately, CRC is likely to be diagnosed at a late stage, increasing CRC-related mortality. However, this alteration in the gut microbiota (gut dysbiosis) can be harnessed as a biomarker for non-invasive diagnosis, prognosis, prevention, and treatment of CRC in an effort to prevent late diagnosis and poor prognosis associated with CRC.<br><br>AIM OF REVIEW: This review discusses identification of potential biomarkers by targeting diet-mediated gut dysbiosis for the stage-specific diagnosis, prognosis, treatment, and prevention of CRC. Our findings provide a comprehensive insight into the potential of protumorigenic bacteria (e.g.pathogenic Escherichia coli,enterotoxigenic Bacteroides fragilis and Fusobacterium nucleatum) and their metabolites (e.g., colibactin and B. fragilis toxin) from gut dysbiosis as biomarkers for the diagnosis of CRC.<br><br>Collectively, a detailed understanding of the available data from current studies suggests that, further research on quantification of metabolites and stage-specific pathogenic microbial abundance is required for the diagnosis and treatment of CRC based on microbial dysbiosis. Specifically, future studies on faecal samples, from patient with CRC, should be conducted for F. nucleatum among different opportunistic bacteria, given its repeated occurrence in faecal samples and CRC biopsies in numerous studies. Finally, we discuss the potential of faecal microbial transplantation (FMT) as an intervention to restore damaged gut microbiota during CRC treatment and management.}, }
@article {pmid36595955, year = {2022}, author = {Lynn, MA and Ryan, FJ and Tee, YC and Lynn, DJ}, title = {Protocol to colonize gnotobiotic mice in early life and assess the impact on early life immune programming.}, journal = {STAR protocols}, volume = {3}, number = {4}, pages = {101914}, pmid = {36595955}, issn = {2666-1667}, mesh = {Animals ; Mice ; *Microbiota ; Fecal Microbiota Transplantation ; Germ-Free Life ; *Gastrointestinal Microbiome ; Feces ; }, abstract = {Understanding how changes in gut microbiota in early life impact immune programming can be difficult to study due to variations in the assembly of the microbiota. In this protocol, we describe how to colonize gnotobiotic/germ-free mice in early life with different microbiota community types (e.g., PAMI and PAMII). We detail several assays to determine whether differential colonization alters immune programming in early life. We also describe how to propagate mouse fecal microbiota transplant material if the donor fecal sample is limited. For complete details on the use and execution of this protocol, please refer to Lynn et al. (2021).[1].}, }
@article {pmid36590421, year = {2022}, author = {Huang, Z and Liu, K and Ma, W and Li, D and Mo, T and Liu, Q}, title = {The gut microbiome in human health and disease-Where are we and where are we going? A bibliometric analysis.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1018594}, pmid = {36590421}, issn = {1664-302X}, abstract = {BACKGROUND: There are trillions of microbiota in our intestinal tract, and they play a significant role in health and disease via interacting with the host in metabolic, immune, neural, and endocrine pathways. Over the past decades, numerous studies have been published in the field of gut microbiome and disease. Although there are narrative reviews of gut microbiome and certain diseases, the whole field is lack of systematic and quantitative analysis. Therefore, we outline research status of the gut microbiome and disease, and present insights into developments and characteristics of this field to provide a holistic grasp and future research directions.<br><br>METHODS: An advanced search was carried out in the Web of Science Core Collection (WoSCC), basing on the term "gut microbiome" and its synonyms. The current status and developing trends of this scientific domain were evaluated by bibliometric methodology. CiteSpace was used to perform collaboration network analysis, co-citation analysis and citation burst detection.<br><br>RESULTS: A total of 29,870 articles and 13,311 reviews were retrieved from the database, which involve 42,900 keywords, 176 countries/regions, 19,065 institutions, 147,225 authors and 4,251 journals. The gut microbiome and disease research is active and has received increasing attention. Co-cited reference analysis revealed the landmark articles in the field. The United States had the largest number of publications and close cooperation with other countries. The current research mainly focuses on gastrointestinal diseases, such as inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), while extra-intestinal diseases are also rising, such as obesity, diabetes, cardiovascular disease, Alzheimer's disease, Parkinson's disease. Omics technologies, fecal microbiota transplantation (FMT) and metabolites linked to mechanism would be more concerned in the future.<br><br>CONCLUSION: The gut microbiome and disease has been a booming field of research, and the trend is expected to continue. Overall, this research field shows a multitude of challenges and great opportunities.}, }
@article {pmid36590298, year = {2022}, author = {Li, Q and Cao, M and Wei, Z and Mei, J and Zhang, Y and Li, M and Li, M and Zhang, Y and Wang, Z}, title = {The protective effect of Buzhong Yiqi decoction on ischemic stroke mice and the mechanism of gut microbiota.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {956620}, pmid = {36590298}, issn = {1662-4548}, abstract = {Buzhong Yiqi decoction (BZYQD) has been developed for preventing or reducing the recurrence of ischemic stroke for a long time in China. However, the mechanism of action of the BZYQD is not completely understood. Our research aims to determine whether the mechanism of action of BZYQD is by regulating gut microbiota using 16SR RNA and fecal microbiota transplantation. In a cerebral ischemia mouse model, the results showed that prophylactic administration of BZYQD could reduce brain infarct volume and improve neurological function and behavior. The prophylactic administration of BZYQD could regulate intestinal microbiota and increase the abundance of butyrate-producing Prevotellaceae_NK3B31_group and probiotic Akkermansia in mice 72 h after surgery. Transplanting BZYQD-administered bacterial flora into antibiotic-depleted mice could reproduce the therapeutic effects of BZYQD. Overall, our study provided molecular insights into the mechanism and impact of BZYQD in the prevention of cerebral ischemic damage and highlighted the potential of regulation of intestinal microbiota as a therapeutic approach for ischemic stroke.}, }
@article {pmid36586523, year = {2023}, author = {Cai, Y and Li, X and Han, Q and Bai, J and Zheng, Q and Sun, R and Liu, R}, title = {Si-Ni-San improves experimental colitis by favoring Akkermensia colonization.}, journal = {Journal of ethnopharmacology}, volume = {305}, number = {}, pages = {116067}, doi = {10.1016/j.jep.2022.116067}, pmid = {36586523}, issn = {1872-7573}, mesh = {Mice ; Animals ; *Colitis/chemically induced/drug therapy/pathology ; *Colitis, Ulcerative/chemically induced/drug therapy/pathology ; *Drugs, Chinese Herbal/therapeutic use ; Inflammation/pathology ; Dextran Sulfate/toxicity ; Mice, Inbred C57BL ; Colon/pathology ; Disease Models, Animal ; }, abstract = {Ulcerative colitis (UC) is widely believed to be a leading risk factor of colorectal cancer. Gut microbiota is a known vital player in the progression of UC. Si-Ni-San (SNS) has been considered to effectively treat colitis in clinical practice during thousands of years, yet whether SNS ameliorated acute colitis mouse model by modulating intestinal flora has not been distinctly elucidated.<br><br>AIM OF THE STUDY: Our study aimed to elucidate the effect of SNS against acute murine colitis and focused on the underlying mechanisms of SNS targeting gut microbiota.<br><br>MATERIALS AND METHODS: 16S RNA sequencing, molecular biological analysis, and fecal microbiota transplants (FMT) were conducted to reveal the mechanisms of SNS in regulating gut microbiota.<br><br>RESULTS: In our study, SNS dramatically inhibited DSS-induced acute inflammatory responses by improving gut microbiota dysbiosis, as evidenced by decreased abundance proinflammatory species, upregulated abundance of anti-inflammatory species and potentially altered microbiota metabolite metabolism. Additionally, intestinal flora knockout and FMT experiments confirmed that the therapeutic effect of SNS on colitis was dependent on gut microbiota, and specifically on favoring the growth of potential probiotics, Akkermansia genus. Furthermore, we found that SNS alone and SNS combined with Akkermansia muciniphila (A. muciniphila) increased Mucin 2 (MUC2) production, thus enhancing the competitive edge of A. muciniphila among pathogenic gut microbiota.<br><br>CONCLUSION: Our study shed lights on the underlying mechanism of SNS in attenuating acute murine colitis from the perspective of intestinal flora and provides novel insights into the discovery of adjacent therapeutic strategy against colitis based on SNS and probiotics.<br><br>CLASSIFICATION: Gastro-intestinal system.}, }
@article {pmid36586452, year = {2023}, author = {Lin, D and Sun, Q and Liu, Z and Pan, J and Zhu, J and Wang, S and Jia, S and Zheng, M and Li, X and Gong, F}, title = {Gut microbiota and bile acids partially mediate the improvement of fibroblast growth factor 21 on methionine-choline-deficient diet-induced non-alcoholic fatty liver disease mice.}, journal = {Free radical biology &amp; medicine}, volume = {195}, number = {}, pages = {199-218}, doi = {10.1016/j.freeradbiomed.2022.12.087}, pmid = {36586452}, issn = {1873-4596}, mesh = {Animals ; Mice ; Bile Acids and Salts/metabolism ; Choline/metabolism ; Diet ; Dysbiosis/drug therapy/metabolism ; *Gastrointestinal Microbiome/physiology ; Liver/metabolism ; Methionine/metabolism ; Mice, Inbred C57BL ; *Non-alcoholic Fatty Liver Disease/metabolism ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, inflammation, and fibrosis, as well as gut dysbiosis. Fibroblast growth factor 21 (FGF21), which regulates glucose and lipid metabolism, has been proven to have a good effect on NAFLD. However, the modulating process between FGF21 and gut microbiota remains unclear in treating NAFLD. Here, the fecal microbiota composition of 30 patients with NAFLD who had undergone liver biopsy and 29 matched healthy participants were studied, together with the fecal bile acid (BA) profile. Treatment with FGF21 was given in methionine-choline-deficient (MCD) diet-induced NAFLD model C57BL/6 mice. An antibiotic cocktail and fecal microbiota transplantation were used to further confirm the benefits of FGF21 that were partially attributable to the change in gut microbiota. Patients with NAFLD had higher serum FGF21 levels and dysregulated fecal microbiota compositions and fecal BA profiles. In NAFLD mice, FGF21 significantly reduced steatohepatitis and collagen deposition in vivo and restored intestinal structure. FGF21 treatment also changed gut microbiota composition and regulated dysbiosis in BA metabolism. After treatment with an antibiotic cocktail, FGF21 partially alleviated hepatic and intestinal damage in NAFLD mice. Furthermore, fecal microbiota transplantation from FGF21-treated mice showed benefits similar to FGF21 therapy. The improvement using FGF21 in MCD diet-induced NAFLD mice is partially mediated via gut microbiota and BA. Gut microbiota-regulated BA metabolism may be a potential target of FGF21 in improving NAFLD.}, }
@article {pmid36585803, year = {2023}, author = {Sun, T and Du, H and Li, Z and Xiong, J and Liu, Y and Li, Y and Zhang, W and Liang, F and He, J and Liu, X and Xiang, H}, title = {Decoding the contributions of gut microbiota and cerebral metabolism in acute liver injury mice with and without cognitive dysfunction.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {29 Suppl 1}, number = {Suppl 1}, pages = {31-42}, pmid = {36585803}, issn = {1755-5949}, support = {81873467//National Natural Science Foundation of China/ ; 21921004//National Natural Science Foundation of China/ ; }, mesh = {Mice ; Male ; Animals ; *Gastrointestinal Microbiome/physiology ; Mice, Inbred C57BL ; Liver ; Fecal Microbiota Transplantation ; *Cognitive Dysfunction ; }, abstract = {AIMS: Patients with acute liver injury (ALI) can develop cognitive dysfunction (CD). The study investigated the role of gut microbiota and cerebral metabolism in ALI mice with and without CD.<br><br>METHODS: Male C57BL/6 mice that received thioacetamide were classified into ALI mice with (susceptible) or without (unsusceptible) CD-like phenotypes by hierarchical cluster analysis of behavior. The role of gut microbiota was investigated by 16S ribosomal RNA gene sequencing and feces microbiota transplantation (FMT). [1] H-[[13] C] NMR and electrophysiology were used to detect the changes in cerebral neurotransmitter metabolic and synaptic transition in neurons or astrocytes.<br><br>RESULTS: Apromixlay 55% (11/20) of mice developed CD and FMT from the susceptible group transmitted CD to gut microbiota-depleted mice. Alloprevotella was enriched in the susceptible group. GABA production was decreased in the frontal cortex, while hippocampal glutamine was increased in the susceptible group. Altered Escherichia. Shigella and Alloprevotella were correlated with behaviors and cerebral metabolic kinetics and identified as good predictors of ALI-induced CD. The frequencies of both miniature inhibitory and excitatory postsynaptic currents in hippocampal CA1 and prefrontal cortex were decreased in the susceptible group.<br><br>CONCLUSION: Altered transmitter metabolism and synaptic transmission in the hippocampus and prefrontal cortex and gut microbiota disturbance may lead to ALI-induced CD.}, }
@article {pmid36585700, year = {2022}, author = {Borgers, JSW and Burgers, FH and Terveer, EM and van Leerdam, ME and Korse, CM and Kessels, R and Flohil, CC and Blank, CU and Schumacher, TN and van Dijk, M and Henderickx, JGE and Keller, JJ and Verspaget, HW and Kuijper, EJ and Haanen, JBAG}, title = {Conversion of unresponsiveness to immune checkpoint inhibition by fecal microbiota transplantation in patients with metastatic melanoma: study protocol for a randomized phase Ib/IIa trial.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {1366}, pmid = {36585700}, issn = {1471-2407}, mesh = {Humans ; Clinical Trials, Phase I as Topic ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces/microbiology ; Immune Checkpoint Inhibitors/therapeutic use ; *Melanoma/therapy/etiology ; *Neoplasms, Second Primary/etiology ; Randomized Controlled Trials as Topic ; *Skin Neoplasms/therapy/etiology ; Treatment Outcome ; Clinical Trials, Phase II as Topic ; Melanoma, Cutaneous Malignant ; }, abstract = {BACKGROUND: The gut microbiome plays an important role in immune modulation. Specifically, presence or absence of certain gut bacterial taxa has been associated with better antitumor immune responses. Furthermore, in trials using fecal microbiota transplantation (FMT) to treat melanoma patients unresponsive to immune checkpoint inhibitors (ICI), complete responses (CR), partial responses (PR), and durable stable disease (SD) have been observed. However, the underlying mechanism determining which patients will or will not respond and what the optimal FMT composition is, has not been fully elucidated, and a discrepancy in microbial taxa associated with clinical response has been observed between studies. Furthermore, it is unknown whether a change in the microbiome itself, irrespective of its origin, or FMT from ICI responding donors, is required for reversion of ICI-unresponsiveness. To address this, we will transfer microbiota of either ICI responder or nonresponder metastatic melanoma patients via FMT.<br><br>METHODS: In this randomized, double-blinded phase Ib/IIa trial, 24 anti-PD1-refractory patients with advanced stage cutaneous melanoma will receive an FMT from either an ICI responding or nonresponding donor, while continuing anti-PD-1 treatment. Donors will be selected from patients with metastatic melanoma treated with anti-PD-1 therapy. Two patients with a good response (&#x2265;&#x2009;30% decrease according to RECIST&#xa0;1.1 within the past 24&#xa0;months) and two patients with progression (&#x2265;&#x2009;20% increase according to RECIST&#xa0;1.1 within the past 3&#xa0;months) will be selected as ICI responding or nonresponding donors, respectively. The primary endpoint is clinical benefit (SD, PR or CR) at 12&#xa0;weeks, confirmed on a CT scan at 16&#xa0;weeks. The secondary endpoint is safety, defined as the occurrence of grade&#x2009;&#x2265;&#x2009;3 toxicity. Exploratory endpoints are progression-free survival and changes in the gut microbiome, metabolome, and immune cells.<br><br>DISCUSSION: Transplanting fecal microbiota to restore the patients' perturbed microbiome has proven successful in several indications. However, less is known about the potential role of FMT to improve antitumor immune response. In this trial, we aim to investigate whether administration of FMT can reverse resistance to anti-PD-1 treatment in patients with advanced stage melanoma, and whether the ICI-responsiveness of the feces donor is associated with its effectiveness.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov: NCT05251389 (registered 22-Feb-2022). Protocol V4.0 (08-02-2022).}, }
@article {pmid36585238, year = {2023}, author = {Hajjar, R and Gonzalez, E and Fragoso, G and Oliero, M and Alaoui, AA and Calvé, A and Vennin Rendos, H and Djediai, S and Cuisiniere, T and Laplante, P and Gerkins, C and Ajayi, AS and Diop, K and Taleb, N and Thérien, S and Schampaert, F and Alratrout, H and Dagbert, F and Loungnarath, R and Sebajang, H and Schwenter, F and Wassef, R and Ratelle, R and Debroux, E and Cailhier, JF and Routy, B and Annabi, B and Brereton, NJB and Richard, C and Santos, MM}, title = {Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines.}, journal = {Gut}, volume = {72}, number = {6}, pages = {1143-1154}, doi = {10.1136/gutjnl-2022-328389}, pmid = {36585238}, issn = {1468-3288}, mesh = {Mice ; Animals ; Cytokines ; *Gastrointestinal Microbiome/physiology ; Retrospective Studies ; RNA, Ribosomal, 16S ; Anastomosis, Surgical/adverse effects ; Anastomotic Leak/microbiology ; *Colorectal Neoplasms/surgery ; }, abstract = {OBJECTIVE: Colorectal cancer (CRC) is the third most diagnosed cancer, and requires surgical resection and reconnection, or anastomosis, of the remaining bowel to re-establish intestinal continuity. Anastomotic leak (AL) is a major complication that increases mortality and cancer recurrence. Our objective is to assess the causal role of gut microbiota in anastomotic healing.<br><br>DESIGN: The causal role of gut microbiota was assessed in a murine AL model receiving faecal microbiota transplantation (FMT) from patients with CRC collected before surgery and who later developed or not, AL. Anastomotic healing and gut barrier integrity were assessed after surgery. Bacterial candidates implicated in anastomotic healing were identified using 16S rRNA gene sequencing and were isolated from faecal samples to be tested both in vitro and in vivo.<br><br>RESULTS: Mice receiving FMT from patients that developed AL displayed poor anastomotic healing. Profiling of gut microbiota of patients and mice after FMT revealed correlations between healing parameters and the relative abundance of Alistipes onderdonkii and Parabacteroides goldsteinii. Oral supplementation with A. onderdonkii resulted in a higher rate of leaks in mice, while gavage with P. goldsteinii improved healing by exerting an anti-inflammatory effect. Patients with AL and mice receiving FMT from AL patients presented upregulation of mucosal MIP-1&#x3b1;, MIP-2, MCP-1 and IL-17A/F before surgery. Retrospective analysis revealed that patients with AL present higher circulating neutrophil and monocyte counts before surgery.<br><br>CONCLUSION: Gut microbiota plays an important role in surgical colonic healing in patients with CRC. The impact of these findings may extend to a vast array of invasive gastrointestinal procedures.}, }
@article {pmid36585105, year = {2023}, author = {Chen, BY and Lin, WZ and Li, YL and Bi, C and Du, LJ and Liu, Y and Zhou, LJ and Liu, T and Xu, S and Shi, CJ and Zhu, H and Wang, YL and Sun, JY and Liu, Y and Zhang, WC and Lu, HX and Wang, YH and Feng, Q and Chen, FX and Wang, CQ and Tonetti, MS and Zhu, YQ and Zhang, H and Duan, SZ}, title = {Roles of oral microbiota and oral-gut microbial transmission in hypertension.}, journal = {Journal of advanced research}, volume = {43}, number = {}, pages = {147-161}, pmid = {36585105}, issn = {2090-1224}, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome/physiology ; RNA, Ribosomal, 16S/genetics ; Cross-Sectional Studies ; Follow-Up Studies ; Mice, Inbred C57BL ; *Microbiota ; *Hypertension ; *Periodontitis ; }, abstract = {INTRODUCTION: Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD is known to aggravate different systematic diseases, but the alteration of oral microbiota in HTN and their impacts on blood pressure (BP) remains to be discovered.<br><br>OBJECTIVES: To characterize the alterations of oral and gut microbiota and their roles in HTN.<br><br>METHODS: We performed a cross-sectional (95 HTN participants and 39 controls) and a 6-month follow-up study (52 HTN participants and 26 controls) to analyze the roles of oral and gut microbiota in HTN. Saliva, subgingival plaques, and feces were collected for 16S rRNA gene sequencing or metagenomic analysis. C57BL/6J mice were pretreated with antibiotics to deplete gut microbiota, and then transplanted with human saliva by gavage to test the impacts of abnormal oral-gut microbial transmission on HTN.<br><br>RESULTS: BP in participants with PD was higher than no PD in both cross-sectional and follow-up cohort. Relative abundances of 14 salivary genera, 15 subgingival genera and 10 gut genera significantly altered in HTN and those of 7 salivary genera, 12 subgingival genera and 6 gut genera significantly correlated with BP. Sixteen species under 5 genera were identified as oral-gut transmitters, illustrating the presence of oral-gut microbial transmission in HTN. Veillonella was a frequent oral-gut transmitter stably enriched in HTN participants of both cross-sectional and follow-up cohorts. Saliva from HTN participants increased BP in hypertensive mice. Human saliva-derived Veillonella successfully colonized in mouse gut, more abundantly under HTN condition.<br><br>CONCLUSIONS: PD and oral microbiota are strongly associated with HTN, likely through oral-gut transmission of microbes. Ectopic colonization of saliva-derived Veillonella in the gut may aggravate HTN. Therefore, precise manipulations of oral microbiota and/or oral-gut microbial transmission may be useful strategies for better prevention and treatment of HTN.}, }
@article {pmid36581371, year = {2022}, author = {Holmstroem, RB and Dahl, EK and Helms, M and Nielsen, HV and Andersen, JB and Bjerrum, JT and Svane, IM and Ellebaek, E and Seidelin, JB}, title = {Tofacitinib and faecal microbiota transplantation in treating checkpoint inhibitor-induced enterocolitis: case report.}, journal = {BMJ open gastroenterology}, volume = {9}, number = {1}, pages = {}, pmid = {36581371}, issn = {2054-4774}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Antineoplastic Agents, Immunological/adverse effects ; *Enterocolitis/chemically induced/therapy ; *Colitis/therapy/drug therapy ; }, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) can induce a wide range of immune-related adverse events (irAEs), potentially affecting any organ. ICI-induced colitis is a frequently reported irAE, whereas enteritis is rare and not well documented.<br><br>CASE PRESENTATION: We are presenting a patient with metastatic melanoma who developed severe ICI-induced enterocolitis multirefractory for glucocorticoids, infliximab and vedolizumab, partially responding to faecal microbiota transplantation and final complete response to tofacitinib.<br><br>CONCLUSION: This case supports that tofacitinib may be an(other) effective agent in managing multirefractory ICI-induced diarrhoea caused by colitis and/or enteritis.}, }
@article {pmid36581324, year = {2023}, author = {Aburahma, A and Stewart, EL and Rana, S and Larsen, R and Ward, CS and Sprague, JE}, title = {Influence of fecal microbial transplant (FMT) between male and female rats on methamphetamine-induced hyperthermia.}, journal = {International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group}, volume = {40}, number = {1}, pages = {2159072}, doi = {10.1080/02656736.2022.2159072}, pmid = {36581324}, issn = {1464-5157}, mesh = {Male ; Female ; Rats ; Animals ; Feces/microbiology ; *Methamphetamine ; RNA, Ribosomal, 16S/genetics ; *Clostridium Infections/microbiology/therapy ; Bacteria ; *Hyperthermia, Induced ; }, abstract = {OBJECTIVE: To investigate the effect of bidirectional fecal microbial transplant (FMT) between male and female rats on methamphetamine (MA)-induced hyperthermia.<br><br>METHODS: FMT was performed between male and female rats prior to MA (10 mg/kg, sc) treatment. Core body temperature, plasma drug and norepinephrine (NE) levels were measured and compared between treatment groups. 16S rRNA gene sequencing of bacterial communities between male and female rats was performed.<br><br>RESULTS: MA treatment resulted in significantly higher core body temperatures in male groups (control and FMT-treated) compared to MA-treated female groups (control and FMT-treated). Plasma concentrations of MA and amphetamine were higher in females than males. Whereas, plasma norepinephrine (NE) levels were not different between male and female rats 90 minutes after MA treatment. At the phyla level, the microbiome of male and female control rats were dominated by Firmicutes and Bacteroidetes. Males had a higher relative abundance of Firmicutes and lower relative abundances of Bacteroidetes than females. The FMT procedure changed the recipient group towards their donor with males getting closer to their donors than females. In the control groups following MA treatment, Firmicutes increased and Bacteroides decreased in females and males. Conversely, in the FMT treatment groups following MA treatment, Firmicutes decreased while Bacteroidetes increased in females and males.<br><br>CONCLUSIONS: Although definite differences in the structure and diversity of the gut microbiome were observed using 16S rRNA gene sequencing of bacterial communities between male and female rats, these differences do not seem to contribute to the sex-based differences in MA-induced hyperthermia.}, }
@article {pmid36580630, year = {2023}, author = {Gulati, AS and Nicholson, MR and Khoruts, A and Kahn, SA}, title = {Fecal Microbiota Transplantation Across the Lifespan: Balancing Efficacy, Safety, and Innovation.}, journal = {The American journal of gastroenterology}, volume = {118}, number = {3}, pages = {435-439}, pmid = {36580630}, issn = {1572-0241}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; R24 AI118629/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Child ; Humans ; Aged ; Fecal Microbiota Transplantation/adverse effects/methods ; Longevity ; *Clostridioides difficile ; Treatment Outcome ; Feces ; *Clostridium Infections/therapy ; Recurrence ; }, abstract = {Fecal microbiota transplantation (FMT) is a rapidly growing therapy aimed at reconstituting the dysbiotic microbiota of a patient with the beneficial stool microbiota of a healthy individual. The efficacy rates of FMT are very robust for recurrent Clostridioides difficile infection in both children and adults. Although complications of FMT have been reported, it is generally believed to be a safe procedure. Novel indications for FMT are being studied, with the hope that ultimately it may be useful for a variety of disorders. As this field continues to grow, however, it is necessary to consider efficacy, safety, and innovation across the lifespan. There are unique concerns regarding FMT as it pertains to children, adults, and the elderly. In this review, we seek to update clinicians, researchers, and regulators on how these factors must be balanced across the lifespan as we move forward with this innovative therapy.}, }
@article {pmid36578000, year = {2022}, author = {Wang, L and Shao, L and Chen, MY and Wang, L and Zhang, W and Tan, FB and Huang, WH}, title = {Effect of ginsenoside compound K on alleviating colitis via modulating gut microbiota.}, journal = {Chinese medicine}, volume = {17}, number = {1}, pages = {146}, pmid = {36578000}, issn = {1749-8546}, support = {82074000//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Ginsenoside compound K (GC-K) potentially alleviates ulcerative colitis involved in gut microbiota, which is significantly associated with the occurrence and development of colitis. However, the effect and mechanism of GC-K on anti-colitis in relation to gut microbiota are not clear. This study focused on the prevention and mechanism of GC-K on Dextran sulfate sodium (DSS)-induced colitis of mice pertinent to gut microbiota.<br><br>METHODS: DSS was used to establish a chronic colitis mouse model. Body weight analysis, colon length measurement, HE staining, and inflammatory factors levels were processed in animal experiments. Flow cytometry was employed to analyze Th17/Treg cells in the mouse spleen and blood. 16S rRNA sequencing was utilized to analyze gut microbiota. Fecal microbiota transplantation (FMT) experiment was employed to verify the anti-colitis efficacy of GC-K by reshaping gut microbiota.<br><br>RESULTS: GC-K significantly relieved colitis-related symptoms due to decreased disease activity index (DAI) scores, spleen weight, and increased colon length. Additionally, the tight junction proteins were increased, and the pro-inflammatory cytokines, such as TNF-&#x3b1;, IL-6, IL-1&#x3b2; and IL-17, were decreased after GC-K treatment. Furthermore, Bacteroides spp. significantly increased after modeling. Moreover, FMT experiments confirmed that GC-K-driven gut microbiota greatly relieved DSS-induced colitis.<br><br>CONCLUSION: GC-K alleviated colitis via the modulation of gut microbiota.}, }
@article {pmid36577369, year = {2022}, author = {Wang, Z and Qin, X and Hu, D and Huang, J and Guo, E and Xiao, R and Li, W and Sun, C and Chen, G}, title = {Akkermansia supplementation reverses the tumor-promoting effect of the fecal microbiota transplantation in ovarian cancer.}, journal = {Cell reports}, volume = {41}, number = {13}, pages = {111890}, doi = {10.1016/j.celrep.2022.111890}, pmid = {36577369}, issn = {2211-1247}, mesh = {Mice ; Animals ; Female ; Humans ; *Fecal Microbiota Transplantation ; Akkermansia ; CD8-Positive T-Lymphocytes ; Feces ; *Ovarian Neoplasms/therapy ; Dietary Supplements ; }, abstract = {Ovarian cancer (OC) remains a clinical challenge for its difficulty in early diagnosis and insensitivity to treatments. Gut microbiota modulate multiple carcinoma progression through immunoregulation. The relationship between OC and gut microbiota has not been fully characterized. We find that the feces of patients with OC demonstrate different characteristics from benign controls. After fecal microbiota transplantation (FMT) from patients with OC into OC-bearing mice, the tumor development accelerates. Further, an Akkermansia supplementation with FMT significantly suppresses OC progression in mice. RNA sequencing of tumors shows that T cell activation pathways are upregulated after Akkermansia supplementation with FMT. Moreover, acetate accumulation accompanies Akkermansia abundance elevation, which is associated with enhanced interferon γ (IFNγ) secretion of CD8[+] T cells and also its tumor-killing property. This work highlights the importance of protective gut microbiome in immune surveillance of OC, which connects accumulation of acetate and the cytotoxic function of CD8[+] T cells by increasing IFNγ secretion.}, }
@article {pmid36576900, year = {2023}, author = {Bier, N and Hanson, B and Jiang, ZD and DuPont, HL and Arias, CA and Miller, WR}, title = {A Case of Successful Treatment of Recurrent Urinary Tract Infection by Extended-Spectrum β-Lactamase Producing Klebsiella pneumoniae Using Oral Lyophilized Fecal Microbiota Transplant.}, journal = {Microbial drug resistance (Larchmont, N.Y.)}, volume = {29}, number = {1}, pages = {34-38}, pmid = {36576900}, issn = {1931-8448}, support = {K08 AI135093/AI/NIAID NIH HHS/United States ; T32 AI055449/AI/NIAID NIH HHS/United States ; TL1 TR003169/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Klebsiella pneumoniae/genetics ; Fecal Microbiota Transplantation/adverse effects ; Anti-Bacterial Agents/pharmacology ; Microbial Sensitivity Tests ; *Urinary Tract Infections/drug therapy ; beta-Lactamases/genetics/therapeutic use ; }, abstract = {Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae UTIs in a patient with an ileal conduit and urostomy. In the 18 months after FMT, the patient had not experienced new infections with ESBL-producing organisms. The urine and stool microbiomes of the patient were tracked before and post-FMT using 16s RNA sequencing with measurement of α-diversity. Sequencing of the recipient microbiota did not mirror the donor stool taxa at either site, but an increase in the relative proportion of the genus Bacteroides as compared with Prevotella was noted in the stool post-transplant. FMTs may be a promising treatment option for recurrent multidrug-resistant infections.}, }
@article {pmid36574857, year = {2023}, author = {Zhang, SL and Cheng, LS and Zhang, ZY and Sun, HT and Li, JJ}, title = {Untangling determinants of gut microbiota and tumor immunologic status through a multi-omics approach in colorectal cancer.}, journal = {Pharmacological research}, volume = {188}, number = {}, pages = {106633}, doi = {10.1016/j.phrs.2022.106633}, pmid = {36574857}, issn = {1096-1186}, mesh = {Humans ; Mice ; Animals ; *Gastrointestinal Microbiome/genetics ; *Colorectal Neoplasms/metabolism ; Multiomics ; Feces ; *Microbiota/genetics ; }, abstract = {The changes in gut microbiota have been implicated in colorectal cancer (CRC). The interplays between the host and gut microbiota remain largely unclear, and few studies have investigated these interplays using integrative multi-omics data. In this study, large-scale multi-comic datasets, including microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing of CRC patients, were analyzed individually and integrated through advanced bioinformatics methods. We further examined the clinical relevance of these findings in the mice recolonized with microbiota from human. We found that CRC patients had distinct microbiota compositions compared to healthy controls. A machine-learning model was developed with 28 biomarkers for detection of CRC, which had high accuracy and clinical applicability. We identified multiple significant correlations between genera and well-characterized genes, suggesting the potential role of gut microbiota in tumor immunity. Further analysis showed that specific metabolites worked as profound communicators between these genera and tumor immunity. Integrating microbiota and metabolome perspectives, we cataloged gut taxonomic and metabolomic features that represented the key multi-omics signature of CRC. Furthermore, gut microbiota transplanted from CRC patients compromised the response of CRC to immunotherapy. These phenotypes were strongly associated with the alterations in gut microbiota, immune cell infiltration as well as multiple metabolic pathways. The comprehensive interplays across multi-comic data of CRC might explain how gut microbiota influenced tumor immunity. Hence, we proposed that modifying the CRC microbiota using healthy donors might serve as a promising strategy to improve response to immunotherapy.}, }
@article {pmid36572703, year = {2022}, author = {Stø, K and Valeur, J and Ueland, T and Malmstrøm, GH and Bjerkeli, V and Trøseid, M and Hov, JR and Holm, K and Vestad, B and Halvorsen, B and Skjelland, M and Skagen, KR}, title = {Fecal level of butyric acid, a microbiome-derived metabolite, is increased in patients with severe carotid atherosclerosis.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {22378}, pmid = {36572703}, issn = {2045-2322}, mesh = {Humans ; Butyric Acid/analysis ; RNA, Ribosomal, 16S/analysis ; Inflammasomes ; *Gastrointestinal Microbiome/physiology ; Fatty Acids, Volatile/metabolism ; *Microbiota ; Feces/chemistry ; *Carotid Artery Diseases ; }, abstract = {The short-chain fatty acid (SCFA) butyric acid maintains a healthy gut barrier and vascular endothelium. We aimed to investigate the association between fecal butyric acid, carotid atherosclerosis and risk factors for ischemic stroke. Patients with severe carotid atherosclerosis (i.e. ≥ 50% stenosis) (n = 43) were compared with healthy controls (n = 38). We analyzed fecal SCFAs by gas chromatography, microbiota composition by 16S rRNA sequencing, markers of gut barrier damage and inflammasome activation by immunoassay, and plasma SCFAs by ultra-high performance liquid chromatography-tandem mass spectroscopy. Patients had higher fecal butyric acid level (p = 0.024), along with increased functional potential of microbial butyric acid production (p = 0.031), compared with controls. Dietary fiber intake was comparable. Patients had higher levels of gut barrier damage markers CCL25 and IFABP, and the inflammasome activation marker IL-18, whereas plasma level of butyric was similar. Increased fecal butyric acid was associated with higher BMI, waist-hip ratio, HbA1c, CRP and leukocyte count. Contrary to our hypothesis, patients with severe carotid atherosclerosis had higher fecal butyric acid level, and increased microbial production, compared with controls. Gut barrier damage in patients might indicate decreased absorption of butyric acid and hence contribute to the higher fecal level.}, }
@article {pmid36572070, year = {2023}, author = {Shon, WJ and Jung, MH and Kim, Y and Kang, GH and Choi, EY and Shin, DM}, title = {Sugar-sweetened beverages exacerbate high-fat diet-induced inflammatory bowel disease by altering the gut microbiome.}, journal = {The Journal of nutritional biochemistry}, volume = {113}, number = {}, pages = {109254}, doi = {10.1016/j.jnutbio.2022.109254}, pmid = {36572070}, issn = {1873-4847}, mesh = {Humans ; Mice ; Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; *Sugar-Sweetened Beverages ; *Colitis/chemically induced/microbiology ; *Inflammatory Bowel Diseases/etiology ; Inflammation ; Sucrose/adverse effects ; Water/adverse effects ; Mice, Inbred C57BL ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; }, abstract = {High-fat diets (HFDs) and frequent consumption of sugar-sweetened beverages (SSBs) are potential contributors to increasing inflammatory bowel disease (IBD) incidences. While HFDs have been implicated in mild intestinal inflammation, the role of sucrose in SSBs remains unclear. Therefore, we studied the role of SSBs in IBD pathogenesis in a mouse model and humans. C57BL6/J mice were given ad libitum access to a sucrose solution or plain water for 10 weeks, with or without an HFD. Interestingly, sucrose solution consumption alone did not induce gut inflammation in mice; however, when combined with an HFD, it dramatically increased the inflammation score, submucosal edema, and CD45[+] cell infiltration. 16S ribosomal RNA gene-sequencing revealed that sucrose solution and HFD co-consumption significantly increased the relative abundance of IBD-related pathogenic bacteria when compared with HFD consumption. RNA sequencing and flow cytometry showed that co-consumption promoted pro-inflammatory cytokine and chemokine synthesis, dendritic-cell expansion, and IFN-γ[+]TNF-α[+]CD4[+] and CD8[+] T-cell activation. Fecal microbiota transplantation from HFD- and sucrose water-fed mice into gut-sterilized mice increased the susceptibility to dextran sulfate sodium-induced colitis in the recipient mice. Consistent herewith, high consumption of SSBs and animal fat-rich diets markedly increased systemic inflammation-associated IBD marker expression in humans. In conclusion, SSBs exacerbate HFD-induced colitis by triggering a shift of the gut microbiome into a pathobiome. Our findings provide new insights for the development of strategies aimed at preventing IBD.}, }
@article {pmid36570710, year = {2022}, author = {Guo, XH and Zhu, YL and Yang, L and Li, WJ and Du, XF}, title = {The Effects of Multi-Donor Fecal Microbiota Transplantation Capsules Combined with Thalidomide on Hormone-Dependent Ulcerative Colitis.}, journal = {Infection and drug resistance}, volume = {15}, number = {}, pages = {7495-7501}, pmid = {36570710}, issn = {1178-6973}, abstract = {OBJECTIVE: This study aimed to assess the effects of multi-donor fecal microbiota transplantation (FMT) capsules combined with thalidomide on hormone-dependent ulcerative colitis (UC).<br><br>METHODS: A total of 59 patients with steroid-dependent UC treated at the Gastroenterology Department of the First Affiliated Hospital of Xinxiang Medical University between January 2017 and January 2019 were enrolled in this study. Using a random number table, the patients were divided into two groups: a group treated with FMT capsules (the FMT group) and a group treated with FMT capsules and thalidomide (the FMT+S group). Multi-donor FMT capsules were prepared, and all subjects and stool donors followed the FMT pathway for FMT transplantation. Each patient's Mayo score, C-reactive protein (CRP) level, and level of fecal calprotectin before FMT treatment and at week 1 and week 13 after treatment were recorded. All patients were followed up for 15 weeks.<br><br>RESULTS: A total of 56.7% of the patients (34/59) achieved a therapeutic response at the end of the research period. Compared with the FMT group, the FMT+S group had better clinical benefit (P < 0.05). In the comparison of efficacy at week 1 and week 13 after treatment, the Mayo scores, calprotectin levels, and CRP indexes in the FMT+S group were better than those in the FMT group (P < 0.05). There were no serious adverse events in the treatment process or during follow-up.<br><br>CONCLUSION: A combination of FMT capsules and thalidomide provides a treatment choice for patients with hormone-dependent UC, and it can be used as an adjuvant therapy. However, large-scale, multi-center, and prospective trials are required to further verify the reliability of this treatment.}, }
@article {pmid36569199, year = {2022}, author = {Hadjadj, L and Cassir, N and Saïdani, N and Hoffman, C and Brouqui, P and Astoul, P and Rolain, JM and Baron, SA}, title = {Outbreak of carbapenem-resistant enterobacteria in a thoracic-oncology unit through clonal and plasmid-mediated transmission of the bla OXA-48 gene in Southern France.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1048516}, pmid = {36569199}, issn = {2235-2988}, mesh = {Humans ; Enterobacteriaceae/genetics ; Carbapenems/pharmacology ; Retrospective Studies ; *Enterobacteriaceae Infections/epidemiology/microbiology ; beta-Lactamases/genetics ; Bacterial Proteins/genetics ; Plasmids/genetics ; Disease Outbreaks ; *Carbapenem-Resistant Enterobacteriaceae/genetics ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Microbial Sensitivity Tests ; }, abstract = {BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) represent an increasing threat to public health, especially in hospitals.<br><br>OBJECTIVES: To investigate an outbreak of CPE in a thoracic-oncology unit by using whole genome sequencing (WGS) and to describe the control measures taken to limit the epidemic, including fecal microbiota transplantation (FMT).<br><br>METHODS: A retrospective study between December 2016 and October 2017 was performed to investigate an outbreak of CPE in a thoracic-oncology unit at the North Hospital in Marseille, France. The isolates were identified, and antimicrobial susceptibility tests were performed. All CPE were sequenced using MiSeq and/or MinIon technologies. Nucleotide variations between plasmids and similarity within the same species were investigated. The origin of this outbreak, its spread, and the decolonization of patients in the ward were also studied.<br><br>RESULTS: Four Citrobacter freundii, one Enterobacter cloacae and four E. hormaechei OXA-48 carbapenemase producers were isolated in eight patients hospitalized the same year in a thoracic-oncology ward. The bla OXA-48 gene was present in a Tn1999.2 transposon located in IncL/M plasmids, with single nucleotide variants (SNV) ranging from 0 to 5. All C. freundii strains belonged to the same ST22 and had more than 99.6% similarity between them. Two strains of E. hormaechei ST1007 were almost identical at 99.98%, while the others belonged to a different ST (ST98, ST114, ST133). No single source was identified. FMT resulted in decolonization in 4/6 patients.<br><br>CONCLUSIONS: WGS demonstrated the dissemination of the bla OXA-48 gene by both clonal (C. freundii ST22 and E. hormaechei ST1007) and plasmid spread (pOXA-48 IncL/M). The origin of this outbreak appeared to be both external and internal to the ward. This evidence of cross-infection supports the urgent need for the implementation of infection control measures to prevent CPE dissemination.}, }
@article {pmid36569149, year = {2022}, author = {Hamamah, S and Gheorghita, R and Lobiuc, A and Sirbu, IO and Covasa, M}, title = {Fecal microbiota transplantation in non-communicable diseases: Recent advances and protocols.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1060581}, pmid = {36569149}, issn = {2296-858X}, abstract = {Fecal microbiota transplant (FMT) is a therapeutic method that aims to restore normal gut microbial composition in recipients. Currently, FMT is approved in the USA to treat recurrent and refractory Clostridioides difficile infection and has been shown to have great efficacy. As such, significant research has been directed toward understanding the potential role of FMT in other conditions associated with gut microbiota dysbiosis such as obesity, type 2 diabetes mellitus, metabolic syndrome, neuropsychiatric disorders, inflammatory bowel disease, irritable bowel syndrome, decompensated cirrhosis, cancers and graft-versus-host disease. This review examines current updates and efficacy of FMT in treating conditions other than Clostridioides difficile infection. Further, protocols for administration of FMT are also discussed including storage of fecal samples in stool banks, inclusion/exclusion criteria for donors, fecal sample preparation and methods of treatment administration. Overall, understanding the mechanisms by which FMT can manipulate gut microbiota to provide therapeutic benefit as well as identifying potential adverse effects is an important step in clarifying its long-term safety and efficacy in treating multiple conditions in the future.}, }
@article {pmid36568836, year = {2022}, author = {Matzaras, R and Nikopoulou, A and Protonotariou, E and Christaki, E}, title = {Gut Microbiota Modulation and Prevention of Dysbiosis as an Alternative Approach to Antimicrobial Resistance: A Narrative Review.}, journal = {The Yale journal of biology and medicine}, volume = {95}, number = {4}, pages = {479-494}, pmid = {36568836}, issn = {1551-4056}, mesh = {Humans ; *Gastrointestinal Microbiome ; Anti-Bacterial Agents/pharmacology ; Dysbiosis/drug therapy/microbiology ; Drug Resistance, Bacterial ; *Probiotics/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Background: The importance of gut microbiota in human health is being increasingly studied. Imbalances in gut microbiota have been associated with infection, inflammation, and obesity. Antibiotic use is the most common and significant cause of major alterations in the composition and function of the gut microbiota and can result in colonization with multidrug-resistant bacteria. Methods: The purpose of this review is to present existing evidence on how microbiota modulation and prevention of gut dysbiosis can serve as tools to combat antimicrobial resistance. Results: While the spread of antibiotic-resistant pathogens requires antibiotics with novel mechanisms of action, the number of newly discovered antimicrobial classes remains very low. For this reason, the application of alternative modalities to combat antimicrobial resistance is necessary. Diet, probiotics/prebiotics, selective oropharyngeal or digestive decontamination, and especially fecal microbiota transplantation (FMT) are under investigation with FMT being the most studied. But, as prevention is better than cure, the implementation of antimicrobial stewardship programs and strict infection control measures along with newly developed chelating agents could also play a crucial role in decreasing colonization with multidrug resistant organisms. Conclusion: New alternative tools to fight antimicrobial resistance via gut microbiota modulation, seem to be effective and should remain the focus of further research and development.}, }
@article {pmid36567449, year = {2023}, author = {Xu, K and Guo, Y and Wang, Y and Ren, Y and Low, V and Cho, S and Ping, L and Peng, K and Li, X and Qiu, Y and Liu, Q and Li, Z and Wang, Z}, title = {Decreased Enterobacteriaceae translocation due to gut microbiota remodeling mediates the alleviation of premature aging by a high-fat diet.}, journal = {Aging cell}, volume = {22}, number = {2}, pages = {e13760}, pmid = {36567449}, issn = {1474-9726}, mesh = {Animals ; Mice ; *Aging, Premature/genetics ; Diet, High-Fat ; Dysbiosis/etiology ; Enterobacteriaceae ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; *Sirtuins ; }, abstract = {Aging-associated microbial dysbiosis exacerbates various disorders and dysfunctions, and is a major contributor to morbidity and mortality in the elderly, but the underlying cause of this aging-related syndrome is confusing. SIRT6 knockout (SIRT6 KO) mice undergo premature aging and succumb to death by 4 weeks, and are therefore useful as a premature aging research model. Here, fecal microbiota transplantation from SIRT6 KO mice into wild-type (WT) mice phenocopies the gut dysbiosis and premature aging observed in SIRT6 KO mice. Conversely, an expanded lifespan was observed in SIRT6 KO mice when transplanted with microbiota from WT mice. Antibiotic cocktail treatment attenuated inflammation and cell senescence in KO mice, directly suggesting that gut dysbiosis contributes to the premature aging of SIRT6 KO mice. Increased Enterobacteriaceae translocation, driven by the overgrowth of Escherichia coli, is the likely mechanism for the premature aging effects of microbiome dysregulation, which could be reversed by a high-fat diet. Our results provide a mechanism for the causal link between gut dysbiosis and aging, and support a beneficial effect of a high-fat diet for correcting gut dysbiosis and alleviating premature aging. This study provides a rationale for the integration of microbiome-based high-fat diets into therapeutic interventions against aging-associated diseases.}, }
@article {pmid36567333, year = {2022}, author = {Su, SH and Wu, YF and Lin, Q and Zhang, L and Wang, DP and Hai, J}, title = {Fecal microbiota transplantation and replenishment of short-chain fatty acids protect against chronic cerebral hypoperfusion-induced colonic dysfunction by regulating gut microbiota, differentiation of Th17 cells, and mitochondrial energy metabolism.}, journal = {Journal of neuroinflammation}, volume = {19}, number = {1}, pages = {313}, pmid = {36567333}, issn = {1742-2094}, support = {81601146//National Natural Science Foundation of China/ ; 81771410//National Natural Science Foundation of China/ ; }, mesh = {Rats ; Animals ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Th17 Cells/metabolism ; RNA, Ribosomal, 16S/metabolism ; Colon/chemistry/metabolism ; Fatty Acids, Volatile/metabolism ; Inflammation/metabolism ; *Brain Ischemia/metabolism ; Energy Metabolism ; Mitochondria/metabolism ; Cell Differentiation ; }, abstract = {BACKGROUND: Little is known about the association between gut microbiota and intestinal injury under a state of chronic cerebral hypoperfusion (CCH). Here, the effects of gut microbiota and short-chain fatty acids (SCFAs), as important metabolic products, on intestinal function and potential mechanisms after CCH were investigated.<br><br>METHODS: Rats were subjected to bilateral common carotid artery occlusion (BCCAo) to induce CCH. The gut microbiota and metabolites of SCFAs were assessed by 16S rRNA sequencing and targeted metabolomics, respectively. Transcriptomic analysis of colon tissues was also conducted. Subsequently, potential molecular pathways and differentially expressed genes were verified by western blot, immunoprecipitation, and immunofluorescence analyses. Furthermore, the integrity of the colonic barrier was evaluated by hematoxylin and eosin and mucin 2 staining and expression levels of tight junction proteins. Besides, colonic inflammation was further assessed by flow cytometry and expression levels of inflammatory cytokines. In addition, colonic mitochondrial dysfunction was analyzed via membrane potential, reactive oxygen species, electron transport chain (ETC) activities, adenosine triphosphate content, and mitochondrial ultrastructure.<br><br>RESULTS: CCH modified gut microbial composition and microbial metabolism of SCFAs, which may be associated with inhibition of mitochondrial ETC activities and oxidative phosphorylation, leading to dysregulation of mitochondrial energy metabolism. Furthermore, CCH induced differentiation of pathogenic Th17 cells, promoted the formation of complexes of interferon regulatory factor 4 and signal transducer and activator of transcription 3 (STAT3), and increased the phosphorylation of STAT3. This was associated with an impairment of colonic barrier function and chronic colonic inflammation. In contrast, FMT and SCFA replenishment ameliorated CCH-induced gut microbial dysbiosis by increasing the intestinal content of Ruminococcus_sp_N15_MGS_57 and modulating microbial metabolism of SCFAs by increasing acetic acid contents associated with an improvment of the balance between Tregs and Th17 cells, mitochondrial ETC activities, and oxidative phosphorylation to prevent colonic inflammation and dysregulation of mitochondrial energy metabolism.<br><br>CONCLUSION: These findings indicate that FMT and SCFA replenishment present a promising therapeutic strategy against colonic dysfunction under a state of chronic cerebral ischemia.}, }
@article {pmid36567320, year = {2022}, author = {Kim, KH and Chung, Y and Huh, JW and Park, DJ and Cho, Y and Oh, Y and Jeong, H and Yoon, J and Kang, JH and Shin, HS and Kim, HC and Kwon, SK and Seo, KY and Oh, SH and Seong, JK and Ha, SJ and Nam, KT and Kim, JF}, title = {Gut microbiota of the young ameliorates physical fitness of the aged in mice.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {238}, pmid = {36567320}, issn = {2049-2618}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Aging/physiology ; *Microbiota ; Fecal Microbiota Transplantation ; Physical Fitness ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Aging is a natural process that an organism gradually loses its physical fitness and functionality. Great efforts have been made to understand and intervene in this deteriorating process. The gut microbiota affects host physiology, and dysbiosis of the microbial community often underlies the pathogenesis of host disorders. The commensal microbiota also changes with aging; however, the interplay between the microbiota and host aging remains largely unexplored. Here, we systematically examined the ameliorating effects of the gut microbiota derived from the young on the physiology and phenotypes of the aged.<br><br>RESULTS: As the fecal microbiota was transplanted from young mice at 5 weeks after birth into 12-month-old ones, the thickness of the muscle fiber and grip strength were increased, and the water retention ability of the skin was enhanced with thickened stratum corneum. Muscle thickness was also marginally increased in 25-month-old mice after transferring the gut microbiota from the young. Bacteria enriched in 12-month-old mice that received the young-derived microbiota significantly correlated with the improved host fitness and altered gene expression. In the dermis of these mice, transcription of Dbn1 was most upregulated and DBN1-expressing cells increased twice. Dbn1-heterozygous mice exhibited impaired skin barrier function and hydration.<br><br>CONCLUSIONS: We revealed that the young-derived gut microbiota rejuvenates the physical fitness of the aged by altering the microbial composition of the gut and gene expression in muscle and skin. Dbn1, for the first time, was found to be induced by the young microbiota and to modulate skin hydration. Our results provide solid evidence that the gut microbiota from the young improves the vitality of the aged. Video Abstract.}, }
@article {pmid36564805, year = {2022}, author = {Li, X and Li, R and Ji, B and Zhao, L and Wang, J and Yan, T}, title = {Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {614}, pmid = {36564805}, issn = {1479-5876}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Gastrointestinal Microbiome/genetics ; Dysbiosis ; Antibodies ; Allografts ; Graft Rejection ; }, abstract = {BACKGROUND: Antibody-mediated rejection (AMR) remains one of the major barriers for graft survival after kidney transplantation. Our previous study suggested a gut microbiota dysbiosis in kidney transplantation recipients with AMR. However, alternations in gut microbial function and structure at species level have not been identified. In the present study, we investigated the metagenomic and metabolic patterns of gut microbiota in AMR patients to provide a comprehensive and in-depth understanding of gut microbiota dysbiosis in AMR.<br><br>METHODS: We enrolled 60 kidney transplantation recipients, 28 showed AMR and 32 were non-AMR controls with stable post-transplant renal functions. Shotgun sequencing and untargeted LC/MS metabolomic profiling of fecal samples were performed in kidney transplantation recipients with AMR and controls.<br><br>RESULTS: Totally, we identified 311 down-regulated and 27 up-regulated gut microbial species associated with AMR after kidney transplantation, resulting in the altered expression levels of 437 genes enriched in 22 pathways, of which 13 were related to metabolism. Moreover, 32 differential fecal metabolites were found in recipients with AMR. Among them, alterations in 3b-hydroxy-5-cholenoic acid, L-pipecolic acid, taurocholate, and 6k-PGF1alpha-d4 directly correlated with changes in gut microbial species and functions. Specific differential fecal species and metabolites were strongly associated with clinical indexes (Cr, BUN, etc.), and could distinguish the recipients with AMR from controls as potential biomarkers.<br><br>CONCLUSIONS: Altogether, our findings provided a comprehensive and in-depth understanding of the correlation between AMR and gut microbiota, which is important for the etiological and diagnostic study of AMR after kidney transplantation.}, }
@article {pmid36564793, year = {2022}, author = {Juottonen, H and Moghadam, NN and Murphy, L and Mappes, J and Galarza, JA}, title = {Host's genetic background determines the outcome of reciprocal faecal transplantation on life-history traits and microbiome composition.}, journal = {Animal microbiome}, volume = {4}, number = {1}, pages = {67}, pmid = {36564793}, issn = {2524-4671}, support = {322536//Academy of Finland/ ; 345091//Academy of Finland/ ; 322536//Academy of Finland/ ; }, abstract = {BACKGROUND: Microbes play a role in their host's fundamental ecological, chemical, and physiological processes. Host life-history traits from defence to growth are therefore determined not only by the abiotic environment and genotype but also by microbiota composition. However, the relative importance and interactive effects of these factors may vary between organisms. Such connections remain particularly elusive in Lepidoptera, which have been argued to lack a permanent microbiome and have microbiota primarily determined by their diet and environment. We tested the microbiome specificity and its influence on life-history traits of two colour genotypes of the wood tiger moth (Arctia plantaginis) that differ in several traits, including growth. All individuals were grown in the laboratory for several generations with standardized conditions. We analyzed the bacterial community of the genotypes before and after a reciprocal frass (i.e., larval faeces) transplantation and followed growth rate, pupal mass, and the production of defensive secretion.<br><br>RESULTS: After transplantation, the fast-growing genotype grew significantly slower compared to the controls, but the slow-growing genotype did not change its growth rate. The frass transplant also increased the volume of defensive secretions in the fast-growing genotype but did not affect pupal mass. Overall, the fast-growing genotype appeared more susceptible to the transplantation than the slow-growing genotype. Microbiome differences between the genotypes strongly suggest genotype-based selective filtering of bacteria from the diet and environment. A novel cluster of insect-associated Erysipelotrichaceae was exclusive to the fast-growing genotype, and specific Enterococcaceae were characteristic to the slow-growing genotype. These Enterococcaceae became more prevalent in the fast-growing genotype after the transplant, which suggests that a&#xa0;slower growth rate is&#xa0;potentially related to their presence.<br><br>CONCLUSIONS: We show that reciprocal frass transplantation can reverse some genotype-specific life-history traits in a lepidopteran host. The results indicate that genotype-specific selective filtering can fine-tune the bacterial community at specific life stages and tissues like the larval frass, even against a background of a highly variable community with stochastic assembly. Altogether, our findings suggest that the host's genotype can influence its susceptibility to being colonized by microbiota, impacting key life-history traits.}, }
@article {pmid36564273, year = {2022}, author = {Stoll, ML}, title = {Therapeutic alteration of the microbiota in rheumatic diseases: Hype or potential?.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {36}, number = {4}, pages = {101806}, doi = {10.1016/j.berh.2022.101806}, pmid = {36564273}, issn = {1532-1770}, mesh = {Humans ; *Microbiota ; Fecal Microbiota Transplantation/adverse effects ; Feces ; *Rheumatic Diseases/therapy ; *Arthritis, Rheumatoid/therapy/etiology ; }, abstract = {Multiple studies have demonstrated abnormalities in the contents of the fecal microbiota in patients with a variety of forms of arthritis. This has prompted interest in microbial-altering therapy as a therapeutic tool. While antibiotics as a long-term therapeutic tool have largely fallen out of favor, there have been multiple studies evaluating probiotics in rheumatoid arthritis, spondyloarthritis, or systemic sclerosis; a small number of studies have tested fecal microbial transplantation (FMT) in rheumatic diseases. Although probiotics were well tolerated, few studies detected meaningful clinical benefit regardless of indication. Likewise, one of the two randomized studies evaluating FMT showed minimal clinical benefit, while the other demonstrated worsening compared to sham treatment. In this review article, I summarize the literature on probiotics and FMT in rheumatic diseases, discuss potential reasons for the absence of demonstrable benefit, and suggest avenues of future direction of research.}, }
@article {pmid36563827, year = {2023}, author = {Deng, J and Zou, X and Liang, Y and Zhong, J and Zhou, K and Zhang, J and Zhang, M and Wang, Z and Sun, Y and Li, M}, title = {Hypoglycemic effects of different molecular weight konjac glucomannans via intestinal microbiota and SCFAs mediated mechanism.}, journal = {International journal of biological macromolecules}, volume = {234}, number = {}, pages = {122941}, doi = {10.1016/j.ijbiomac.2022.12.160}, pmid = {36563827}, issn = {1879-0003}, mesh = {Rats ; Animals ; Hypoglycemic Agents/pharmacology ; *Gastrointestinal Microbiome ; Molecular Weight ; Fatty Acids, Volatile/metabolism ; *Diabetes Mellitus ; Bile Acids and Salts/pharmacology ; }, abstract = {The hypoglycemic effects of konjac glucomannans (KGMs) are well recognized, and our previous study showed KGMs with different molecular weight have different hypoglycemic effects on diabetes rats, but the detailed mechanisms still remain unclear. In this study, KGMs with medium molecular weight (KGM-M, 757.1 kDa) and low molecular weight (KGM-L, 87.3 kDa) were utilized to investigate the possible mechanism on hypoglycemic effects of type 2 diabetic (T2DM) rats. The results revealed that KGM-M had better effects than KGM-L on decreasing fasting blood glucose, mitigating insulin resistance and improving inflammation. Further mechanism analysis showed that KGM-M better enriched gut flora diversity and the abundance of Ruminococcus and Lachnoclostridium, which was accompanied by increased short chain fatty acids (SCFAs) production and expression of G protein-coupled receptors (GPCRs), and improved regulation on bile acid synthesis. Antibiotics treatment eliminated the beneficial effects of KGMs on gut flora, SCFAs, GPCRs and bile acid synthesis. By contrast, fecal microbiota transplantation (FMT) treatment restored the structure of intestinal microbiota. And after FMT treatment, KGM-M displayed higher hypoglycemic activity than KGM-L, probably due to the better effects on intestinal microbiota, SCFAs production, GPCRs expression and bile acid synthesis inhibition.}, }
@article {pmid36561896, year = {2022}, author = {Elsayed, OH and Ercis, M and Pahwa, M and Singh, B}, title = {Treatment-Resistant Bipolar Depression: Therapeutic Trends, Challenges and Future Directions.}, journal = {Neuropsychiatric disease and treatment}, volume = {18}, number = {}, pages = {2927-2943}, pmid = {36561896}, issn = {1176-6328}, abstract = {INTRODUCTION: Bipolar disorder (BD) is a chronic mental illness impacting 1-2% of the population worldwide and causing high rates of functional impairment. Patients with BD spend most of their time in depressive episodes and up to one-third of patients do not respond to adequate doses of medications. Although no consensus exists for definition of treatment-resistant bipolar depression (TRBD), failure of symptoms improvement despite an adequate trial of two therapeutic agents is a common theme of TRBD. In this paper, we review the evidence base of therapeutic interventions, challenges, and potential future directions for TRBD.<br><br>METHODS: We conducted a literature search for randomized controlled trials on PubMed for the treatment of TRBD and ongoing trials for the treatment of TRBD/bipolar depression on clinicaltrials.gov.<br><br>RESULTS: Several therapeutic agents have been investigated for TRBD. Adjunctive pramipexole and modafinil have data supporting short-term efficacy in TRBD, along with limited data for racemic intravenous ketamine. Celecoxib augmentation of escitalopram and treatment with metformin in patients with insulin resistance showed promising results. Right unilateral electroconvulsive therapy displayed statistically significant response rate and improvement, but not remission compared to pharmacotherapy. Trials for transcranial magnetic stimulation (TMS) have failed to show a significant difference from sham treatment in TRBD.<br><br>FUTURE TRENDS: Pharmacological treatments with novel mechanisms of actions like brexpiprazole and vortioxetine are being investigated following successes in unipolar depression. Modified TMS protocols such as accelerated TMS are under investigation. Innovative approaches like psychedelic-assisted psychotherapy, interleukin-2, fecal microbiota transplantation and multipotent stromal cells are being studied.<br><br>CONCLUSION: Evidence on current treatment modalities for TRBD is limited with low efficacy. More research is needed for successful treatment of TRBD. Effective therapies and innovative approaches to treatment are being investigated and could show promise.}, }
@article {pmid36561217, year = {2022}, author = {Zhang, Y and Zhou, Y and Cui, W and Wang, Z and Wang, X and Wu, F and Wang, P and Wang, T and Yu, W and Wang, L and Shang, J and Zhao, Z}, title = {Characterization and diagnostic value of the gut microbial composition in patients with minimal change disease.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {1070569}, pmid = {36561217}, issn = {1664-042X}, abstract = {Background: Minimal change disease (MCD) is one of the most common causes of primary nephrotic syndrome with high morbidity. This study aimed to explore the typical alterations of gut microbiota in MCD and establish a non-invasive classifier using key gut microbiome. We also aimed to evaluate the therapeutic efficiency of gut microbiota intervention in MCD through animal experiments. Methods: A total of 222 stool samples were collected from MCD patients and healthy controls at the First Affiliated Hospital of Zhengzhou University and Shandong Provincial Hospital for 16S rRNA sequencing. Optimum operational taxonomic units (OTUs) were obtained for constructing a diagnostic model. MCD rat models were established using doxorubicin hydrochloride for exploring the therapeutic efficiency of gut microbial intervention through fecal microbiota transplantation (FMT). Results: The α-diversity of gut microbiota decreased in MCD patients when compared with healthy controls. The relative abundance of bacterial species also changed significantly. We constructed a diagnostic model based on eight optimal OTUs and it achieved efficiency of 97.81% in discovery cohort. The high efficiency of diagnostic model was also validated in the patients with different disease states and cross-regional cohorts. The treatment partially recovered the gut microbial dysbiosis in patients with MCD. In animal experiments, likewise, the gut microbiota changed sharply in MCD rats. However, gut microbial interventions did not reduce urinary protein or pathological kidney damage. Conclusion: Gut Microbiota shifts sharply in both patients and rats with MCD. Typical microbial changes can be used as biomarkers for MCD diagnosis. The gut microbiota compositions in patients with MCD tended to normalize after treatment. However, the intervention of gut microbiota seems to have no therapeutic effect on MCD.}, }
@article {pmid36560636, year = {2022}, author = {Ács, N and Holohan, R and Dunne, LJ and Fernandes, AR and Clooney, AG and Draper, LA and Ross, RP and Hill, C}, title = {Comparing In Vitro Faecal Fermentation Methods as Surrogates for Phage Therapy Application.}, journal = {Viruses}, volume = {14}, number = {12}, pages = {}, pmid = {36560636}, issn = {1999-4915}, mesh = {Humans ; Fermentation ; *Phage Therapy ; Feces ; Gastrointestinal Tract ; *Bacteriophages/genetics ; }, abstract = {The human microbiome and its importance in health and disease have been the subject of numerous research articles. Most microbes reside in the digestive tract, with up to 10[12] cells per gram of faecal material found in the colon. In terms of gene number, it has been estimated that the gut microbiome harbours >100 times more genes than the human genome. Several human intestinal diseases are strongly associated with disruptions in gut microbiome composition. Less studied components of the gut microbiome are the bacterial viruses called bacteriophages that may be present in numbers equal to or greater than the prokaryotes. Their potential to lyse their bacterial hosts, or to act as agents of horizontal gene transfer makes them important research targets. In this study in vitro faecal fermentation systems were developed and compared for their ability to act as surrogates for the human colon. Changes in bacterial and viral composition occurred after introducing a high-titre single phage preparation both with and without a known bacterial host during the 24 h-long fermentation. We also show that during this timeframe 50 mL plastic tubes can provide data similar to that generated in a sophisticated faecal fermenter system. This knowledge can guide us to a better understanding of the short-term impact of bacteriophage transplants on the bacteriomes and viromes of human recipients.}, }
@article {pmid36558532, year = {2022}, author = {Komorniak, N and Martynova-Van Kley, A and Nalian, A and Wroński, M and Kaseja, K and Kowalewski, B and Kaźmierczak-Siedlecka, K and Łoniewski, I and Kaczmarczyk, M and Podsiadło, K and Bogdański, P and Palma, J and Stachowska, E}, title = {Association between Fecal Microbiota, SCFA, Gut Integrity Markers and Depressive Symptoms in Patients Treated in the Past with Bariatric Surgery-The Cross-Sectional Study.}, journal = {Nutrients}, volume = {14}, number = {24}, pages = {}, pmid = {36558532}, issn = {2072-6643}, mesh = {Adult ; Humans ; Cross-Sectional Studies ; *Gastric Bypass ; Depression/etiology ; *Bariatric Surgery/adverse effects ; *Gastrointestinal Microbiome ; Fatty Acids, Volatile ; *Obesity, Morbid/surgery ; }, abstract = {(1) Background: Depressive symptoms often appear after surgical treatment. (2) Methods: We involved 41 adults who underwent bariatric surgery a minimum of 6 months before the study and had the Beck scale ≥12. We analysed patients' mental state, gut barrier markers, faecal short chain fatty acids, and microbiota. (3) Results: Gut microbiota composition differed significantly among patients undergoing two different types of surgery (F = 1.64, p = 0.00002). Additionally, we discovered an association between short chain fatty acids and the Beck scale (F = 1.22, p = 0.058). The rearrangement of bacterial metabolites may be due to the patients' use of increased dietary protein, with insufficient intake of products containing vegetable fiber (Diet Quality Index (DQI-I)adequacy 22.55 (±3.46) points). (4) Conclusions: Bariatric surgery affects the gut microbiota, which may play an important role in the development of depressive and gastrointestinal symptoms in patients after bariatric surgery. Low fiber consumption and increased levels of faecal isobutyric acid may lead to intestinal inflammation. There is a need for further research on this topic including a larger sample size.}, }
@article {pmid36558359, year = {2022}, author = {Bustamante, JM and Dawson, T and Loeffler, C and Marfori, Z and Marchesi, JR and Mullish, BH and Thompson, CC and Crandall, KA and Rahnavard, A and Allegretti, JR and Cummings, BP}, title = {Impact of Fecal Microbiota Transplantation on Gut Bacterial Bile Acid Metabolism in Humans.}, journal = {Nutrients}, volume = {14}, number = {24}, pages = {}, pmid = {36558359}, issn = {2072-6643}, support = {MC_PC_12025/MRC_/Medical Research Council/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; R21 AT010956/AT/NCCIH NIH HHS/United States ; R21AT010956/NH/NIH HHS/United States ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Feces/microbiology ; Bacteria/genetics ; Bile Acids and Salts/analysis ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients in which we found that FMT enhanced gut bacterial bile acid metabolism and delayed the development of impaired glucose tolerance relative to the placebo control group. Therefore, we conducted a secondary analysis of fecal samples collected from these patients to assess the potential gut microbial species contributing to the effect of FMT to improve metabolic health and increase gut bacterial bile acid metabolism. Fecal samples collected at baseline and after 4 weeks of FMT or placebo treatment underwent shotgun metagenomic analysis. Ultra-high-performance liquid chromatography-mass spectrometry was used to profile fecal bile acids. FMT-enriched bacteria that have been implicated in gut bile acid metabolism included Desulfovibrio fairfieldensis and Clostridium hylemonae. To identify candidate bacteria involved in gut microbial bile acid metabolism, we assessed correlations between bacterial species abundance and bile acid profile, with a focus on bile acid products of gut bacterial metabolism. Bacteroides ovatus and Phocaeicola dorei were positively correlated with unconjugated bile acids. Bifidobacterium adolescentis, Collinsella aerofaciens, and Faecalibacterium prausnitzii were positively correlated with secondary bile acids. Together, these data identify several candidate bacteria that may contribute to the metabolic benefits of FMT and gut bacterial bile acid metabolism that requires further functional validation.}, }
@article {pmid36557703, year = {2022}, author = {Tun, KM and Hsu, M and Batra, K and Lo, CH and Laeeq, T and Vongsavath, T and Mohammed, S and Hong, AS}, title = {Efficacy and Safety of Fecal Microbiota Transplantation in Treatment of Clostridioides difficile Infection among Pediatric Patients: A Systematic Review and Meta-Analysis.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557703}, issn = {2076-2607}, abstract = {Background and Aims: Cases of Clostridioides difficile infection have been rising among the pediatric and adolescent population. Fecal microbiota transplantation (FMT) has emerged as an alternative therapy for recurrent C. difficile infection. We aim to perform the first systematic review and meta-analysis investigating the safety and efficacy of fecal microbiota transplantation for C. difficile infection in children and adolescents. Methods: A literature search was performed using variations of the keywords “pediatrics”, “C. difficile infection”, and “fecal microbiota transplantation” in PubMed, EMBASE, CINAHL, Cochrane, and Google Scholar from inception to 30 June 2022. The resulting 575 articles were independently screened by three authors. Fourteen studies that satisfied the eligibility criteria were included in the meta-analysis. Results: The pooled success rate of FMT in the overall cohort was 86% (95% confidence interval: 77−95%; p < 0.001; I2 = 70%). There were 38 serious adverse events in 36 patients with a pooled rate of 2.0% (95% confidence interval: 0.0−3.0%; p = 0.1; I2 = 0.0%) and 47 adverse events in 45 patients with a pooled rate of 15% (95% confidence interval: 5.0−25.0%; p = 0.02; I2 = 54.0%). There was no death associated with FMT. Conclusions: FMT was concluded to be an effective and safe therapy in pediatric and adolescent patients with C. difficile infection. Underlying comorbidities may impede the efficacy. A rigorous screening process of the donors is recommended prior to embarking on FMT. There is no universal and cost-effective way to monitor the long-term outcomes of FMT. While promising, metagenomic sequencing may not be available in settings with limited resources. Robust data from randomized clinical trials is warranted.}, }
@article {pmid36557677, year = {2022}, author = {Quaranta, G and Guarnaccia, A and Fancello, G and Agrillo, C and Iannarelli, F and Sanguinetti, M and Masucci, L}, title = {Fecal Microbiota Transplantation and Other Gut Microbiota Manipulation Strategies.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557677}, issn = {2076-2607}, abstract = {The gut microbiota is composed of bacteria, archaea, phages, and protozoa. It is now well known that their mutual interactions and metabolism influence host organism pathophysiology. Over the years, there has been growing interest in the composition of the gut microbiota and intervention strategies in order to modulate it. Characterizing the gut microbial populations represents the first step to clarifying the impact on the health/illness equilibrium, and then developing potential tools suited for each clinical disorder. In this review, we discuss the current gut microbiota manipulation strategies available and their clinical applications in personalized medicine. Among them, FMT represents the most widely explored therapeutic tools as recent guidelines and standardization protocols, not only for intestinal disorders. On the other hand, the use of prebiotics and probiotics has evidence of encouraging findings on their safety, patient compliance, and inter-individual effectiveness. In recent years, avant-garde approaches have emerged, including engineered bacterial strains, phage therapy, and genome editing (CRISPR-Cas9), which require further investigation through clinical trials.}, }
@article {pmid36557658, year = {2022}, author = {Talapko, J and Včev, A and Meštrović, T and Pustijanac, E and Jukić, M and Škrlec, I}, title = {Homeostasis and Dysbiosis of the Intestinal Microbiota: Comparing Hallmarks of a Healthy State with Changes in Inflammatory Bowel Disease.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557658}, issn = {2076-2607}, abstract = {The gut microbiota, which represent a community of different microorganisms in the human intestinal tract, are crucial to preserving human health by participating in various physiological functions and acting as a metabolic organ. In physiological conditions, microbiota-host partnership exerts homeostatic stability; however, changes in intestinal microbiota composition (dysbiosis) are an important factor in the pathogenesis of inflammatory bowel disease and its two main disease entities: ulcerative colitis and Crohn's disease. The incidence and prevalence of these inflammatory conditions have increased rapidly in the last decade, becoming a significant problem for the healthcare system and a true challenge in finding novel therapeutic solutions. The issue is that, despite numerous studies, the etiopathogenesis of inflammatory bowel disease is not completely clear. Based on current knowledge, chronic intestinal inflammation occurs due to altered intestinal microbiota and environmental factors, as well as a complex interplay between the genetic predisposition of the host and an inappropriate innate and acquired immune response. It is important to note that the development of biological and immunomodulatory therapy has led to significant progress in treating inflammatory bowel disease. Certain lifestyle changes and novel approaches-including fecal microbiota transplantation and nutritional supplementation with probiotics, prebiotics, and synbiotics-have offered solutions for dysbiosis management and paved the way towards restoring a healthy microbiome, with only minimal long-term unfavorable effects.}, }
@article {pmid36556089, year = {2022}, author = {Mirsepasi-Lauridsen, HC}, title = {Therapy Used to Promote Disease Remission Targeting Gut Dysbiosis, in UC Patients with Active Disease.}, journal = {Journal of clinical medicine}, volume = {11}, number = {24}, pages = {}, pmid = {36556089}, issn = {2077-0383}, support = {39800705_814_Patentvoucher//Danish Erhvershuset-Patentvoucher 2022/ ; }, abstract = {Ulcerative colitis (UC) is a relapsing non-transmural chronic inflammatory disease of the colon characterized by bloody diarrhea. The etiology of UC is unknown. The goal is to reduce the inflammation and induce disease remission in UC patients with active disease. The aim of this study is to investigate the innovative treatment method used to promote disease remission in UC patients with active disease targeting gut dysbiosis. Immunosuppressants such as TNF-α blocker are used to promote disease remission in UC, but it is expensive and with side effects. Probiotic, prebiotic and diet are shown to be effective in maintaining disease remission. Fecal microbiota transplantation (FMT) might be the future therapy option to promote disease remission in UC patients with active disease. However, correct manufacturing and administration of the FMT are essential to achieve successful outcome. A few cohorts with FMT capsules show promising results in UC patients with active disease. However, randomized controlled clinical trials with long-term treatment and follow-up periods are necessary to show FMT capsules' efficacy to promote disease remission in UC patients.}, }
@article {pmid36555774, year = {2022}, author = {Nita, IB and Ilie, OD and Ciobica, A and Hritcu, LD and Dobrin, I and Doroftei, B and Dobrin, R}, title = {Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia.}, journal = {International journal of molecular sciences}, volume = {23}, number = {24}, pages = {}, pmid = {36555774}, issn = {1422-0067}, mesh = {Humans ; *Schizophrenia/drug therapy ; *Gastrointestinal Microbiome ; *Antipsychotic Agents/therapeutic use ; Olanzapine ; *Clozapine/therapeutic use ; *Probiotics/therapeutic use ; Prebiotics ; }, abstract = {Schizophrenia (SCZ) is a severe brain disorder characterized by an intriguing clinical panel that has begun to gain interest due to its particular phenotype. Having considered the role of gut microflora in psychiatry, the latest discoveries might offer further insight into the underlying mechanisms. Thus, we aimed to offer an updated overview of the therapeutic potential of microorganism-derived supplements alongside dedicated protocols that target the re-establishment of the host's eubiosis. Based on combinations of specific keywords, we performed searches in four databases (PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect) for the established interval (2018-2022) and identified twenty two eligible cases, restricted only to human patients' experiences. Up until the writing of this manuscript, it has been revealed that the administration of specific lactic acid bacteria strains (Lactobacillus and Bifidobacterium), or those combined with vitamin D and selenium, maintain the integrity of the gut flora, preventing antagonistic effects including inflammation, antipsychotic-related body weight gain (olanzapine) and other metabolic dysfunctionalities. However, there are multiple antipsychotics that exert a potent effect upon gut flora, influencing a plethora of pathways and creating a dysbalance ratio between beneficial and opportunistic pathogens. Risperidone, amisulpride, and clozapine are just a few examples, but the current literature is unfortunately inconsistent and reported data is contradictory, which is why we support additional studies in this context. Moreover, we further argue the utility of studying how distinct controlled substances influence microbial communities, considering that ketamine is proved to alleviate depressive-like behavior as opposed to amphetamine and phencyclidine, which are known substances to trigger SCZ-like symptoms in experimental models. Probiotics may be regarded as the most consequential vehicle through which the gut flora can be successfully influenced, in adequate doses exerting a beneficial role as an alternative approach to alleviate SCZ symptoms.}, }
@article {pmid36555600, year = {2022}, author = {Tyszka, M and Maciejewska-Markiewicz, D and Biliński, J and Lubas, A and Stachowska, E and Basak, GW}, title = {Increased Intestinal Permeability and Stool Zonulin, Calprotectin and Beta-Defensin-2 Concentrations in Allogenic Hematopoietic Cell Transplantation Recipients.}, journal = {International journal of molecular sciences}, volume = {23}, number = {24}, pages = {}, pmid = {36555600}, issn = {1422-0067}, support = {UMO-2018/29/N/NZ5/01779//National Science Center/ ; }, mesh = {Humans ; *beta-Defensins ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; *Graft vs Host Disease/etiology ; Permeability ; }, abstract = {Significant progress has been made in understanding the connection between intestinal barrier function and allogenic hematopoietic cell transplantation (allo-HCT) recipients' outcomes. The purpose of this study was to further evaluate gut barrier permeability and other potential intestinal barrier disruption markers in the allo-HCT setting. Fifty-one patients were enrolled in the study. Intestinal permeability was assessed with the sugar absorption test and faecal concentrations of the zonulin, calprotectin and beta-defensin-2 levels in the peri-transplantation period. Most patients undergoing allo-HCT in our department had a disrupted intestinal barrier at the baseline, which was associated with older age and higher Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). Regardless of this, we observed a further increase in gut barrier permeability after allo-HCT in most patients. However, there was no association between permeability assay and other markers (zonulin, calprotectin and beta-defensin-2). Patients with acute GVHD had significantly higher median calprotectin concentrations after allo-HCT compared with the patients without this complication. Our findings indicate that gut barrier damage develops prior to allo-HCT with progression after the procedure and precedes further complications, but did not prove other markers to be useful surrogates of intestinal permeability.}, }
@article {pmid36552041, year = {2022}, author = {Patel, D and Desai, C and Singh, D and Soppina, V and Parwani, K and Patel, F and Mandal, P}, title = {Synbiotic Intervention Ameliorates Oxidative Stress and Gut Permeability in an In Vitro and In Vivo Model of Ethanol-Induced Intestinal Dysbiosis.}, journal = {Biomedicines}, volume = {10}, number = {12}, pages = {}, pmid = {36552041}, issn = {2227-9059}, abstract = {Alcoholic liver disease (ALD) alters gut microbiota and tight junctions, causing bacterial components to enter the portal vein and induce oxidative stress-induced inflammation in the liver. Only corticosteroids and liver transplants are treatment options for severe alcoholic hepatitis. ALD's pathophysiology is unknown. However, acetaldehyde's toxic effects cause oxidative stress and intestinal permeability. This study investigates the influence of a synbiotic (a combination of aged garlic extract (AGE) and Lactobacillus rhamnosus MTCC1423) on colonic oxidative stress and inflammation in ALD male Wistar rats and Caco2 cells. MDA measurement by HPLC in CaCo2 cells, blood serum, and colon tissue demonstrated that synbiotic treatment in the ALD model reduces oxidative stress. Further, fecal high-throughput 16S rRNA gene sequencing revealed the microbiome's shift towards Firmicutes in the synbiotic group compared to ethanol. In addition, DCFDA labeling and H/E staining demonstrate that the synbiotic is beneficial in inhibiting the development of ALD. In the colon, the synbiotic reduces the activation of CYP2E1 and the inflammatory markers TNF-a and IL-6 while elevating the mRNA expression of ZO-1, occludin, and IL-10. Synbiotics colonize Lactobacillus to restore barrier function and microbiota and reduce colon oxidative stress. Thus, a synbiotic combination can be used in ALD treatment.}, }
@article {pmid36552029, year = {2022}, author = {Feng, J and Ma, H and Huang, Y and Li, J and Li, W}, title = {Ruminococcaceae_UCG-013 Promotes Obesity Resistance in Mice.}, journal = {Biomedicines}, volume = {10}, number = {12}, pages = {}, pmid = {36552029}, issn = {2227-9059}, abstract = {Alterations in the gut microbiome have been linked to obesity and type 2 diabetes, in epidemiologic studies and studies of fecal transfer effects in germ-free mice. Here, we aimed to identify the effects of specific gut microbes on the phenotype of mice fed a high-fat diet (HFD). After eight weeks of HFD feeding, male C57BL/6J mice in the HFD group ranking in the upper and lower quartiles for body weight gain were considered obese prone and obese resistant, respectively. 16S rRNA gene sequencing was used to determine the composition of the intestinal microbiota, and fecal transplantation (FMT) was conducted to determine whether the microbiota plays a causal role in phenotypic variation. Ruminococcaceae_UCG-013 was more abundant in the gut microbes of mice with a lean phenotype than in those with an obese phenotype. Ruminococcaceae_UCG-013 was identified as the most significant biomarker for alleviating obesity by random forest analysis. In a correlation analysis of serum parameters and body weight, Ruminococcaceae_UCG-013 was positively associated with serum HDL-C levels and negatively associated with serum TC, TG, and LDL-C levels. To conclude, Ruminococcaceae_UCG-013 was identified as a novel microbiome biomarker for obesity resistance, which may serve as a basis for understanding the critical gut microbes responsible for obesity resistance. Ruminococcaceae_UCG-013 may serve as a target for microbiome-based diagnoses and treatments in the future.}, }
@article {pmid36551772, year = {2022}, author = {Tian, P and Gao, J and Liang, L and Cui, B and Hu, Q and Zhou, W and Li, B and Liu, Y and Chen, T and Rao, J and Wei, H}, title = {Fecal Microbiota Transplantation Could Improve Chronic Diarrhea in Cynomolgus Monkey by Alleviating Inflammation and Modulating Gut Microbiota.}, journal = {Biomedicines}, volume = {10}, number = {12}, pages = {}, pmid = {36551772}, issn = {2227-9059}, support = {2021YFA0805904//National Key Research and Development Program/ ; 82200966//National Natural Science Foundation of China/ ; SKLRD-OP-202104//Open Project of State Key Laboratory of Respiratory Diseases/ ; }, abstract = {Chronic diarrhea is associated with enteric dysbiosis and provokes the overuse of antibiotics. Fecal microbiota transplantation (FMT) is a promising therapy, but it shows discrepant clinical efficacy. Bacterial colonization in recipients has been studied, although little is known about the role of gut fungi and Archaea after FMT. In this study, we evaluated the efficacy of human-derived FMT on spontaneous chronic diarrhea cynomolgus monkeys and revealed the effector mechanisms. We demonstrated that FMT can mitigate the appearance of diarrheal symptoms and inhibit the increase in interleukin-6, interleukin-8, interleukin-1β, and interferon-γ and the decrease in interleukin-10 in serum. We confirmed that FMT restored the disturbance of gut bacteria by reducing the relative abundances of potential pathogens, including Cloacibacillus porcorum, Desulfovibrio desulfuricans, Erysipelotrichaceae bacterium 5_2_54FAA, and Erysipelotrichaceae bacterium 21_3, and increasing the levels of Lactobacillus fermentum and Lactobacillus ruminis CAG_367 in diarrheal monkeys. The metabolic pathways of healthy and FMT monkeys' gut bacteria were enriched in amino acid metabolism, carbohydrate metabolism, and lipid metabolism, while the metabolic pathways of pre-FMT monkeys' gut bacteria were enriched in antibiotic production. Moreover, a higher Ascomycota/Basidiomycota ratio, higher Aspergillus levels, and lower Trichosporon asahii abundance were present in intestinal fungi after FMT. Although the abundance of the Archaea Methanosphaera stastmanae did not change significantly, it was inversely correlated with the anti-inflammatory factor IL-4 after FMT. These results support the further development and application of FMT for chronic diarrhea.}, }
@article {pmid36551258, year = {2022}, author = {Petakh, P and Isevych, V and Kamyshnyi, A and Oksenych, V}, title = {Weil's Disease-Immunopathogenesis, Multiple Organ Failure, and Potential Role of Gut Microbiota.}, journal = {Biomolecules}, volume = {12}, number = {12}, pages = {}, pmid = {36551258}, issn = {2218-273X}, mesh = {Humans ; *Weil Disease/pathology ; *Gastrointestinal Microbiome ; Multiple Organ Failure/pathology ; *Leptospirosis ; Liver/pathology ; }, abstract = {Leptospirosis is an important zoonotic disease, causing about 60,000 deaths annually. In this review, we have described in detail the immunopathogenesis of leptospirosis, the influence of cytokines, genetic susceptibility on the course of the disease, and the evasion of the immune response. These data are combined with information about immunological and pathomorphological changes in the kidneys, liver, and lungs, which are most affected by Weil's disease. The review also suggests a possible role of the gut microbiota in the clinical course of leptospirosis, the main mechanisms of the influence of gut dysbiosis on damage in the liver, kidneys, and lungs through several axes, i.e., gut-liver, gut-kidney, and gut-lungs. Modulation of gut microbiota by probiotics and/or fecal microbiota transplantation in leptospirosis may become an important area of scientific research.}, }
@article {pmid36550632, year = {2023}, author = {Li, J and Liang, J and Zeng, M and Sun, K and Luo, Y and Zheng, H and Li, F and Yuan, W and Zhou, H and Liu, J and Sun, H}, title = {Oxymatrine ameliorates white matter injury by modulating gut microbiota after intracerebral hemorrhage in mice.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {29 Suppl 1}, number = {Suppl 1}, pages = {18-30}, pmid = {36550632}, issn = {1755-5949}, support = {2020A1515010038//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2018B030340001//Key-Area Research and Development Program of Guangdong Province/ ; yzjj2018rc03//Presidential Foundation of Zhujiang Hospital, Southern Medical University/ ; GDHVPS2018//Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme/ ; 2019-QNRC2-C14//Young Elite Scientists Sponsorship Program by CACM/ ; Z20211397//Scientific research project funded by health Commission of Guangxi Zhuang Autonomous Region, China/ ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; *White Matter/pathology ; Dysbiosis/drug therapy ; Cerebral Hemorrhage/drug therapy/pathology ; *Brain Injuries/pathology ; Inflammation/pathology ; *Gastrointestinal Diseases ; }, abstract = {INTRODUCTION: White matter injury (WMI) significantly affects neurobehavioral recovery in intracerebral hemorrhage (ICH) patients. Gut dysbiosis plays an important role in the pathogenesis of neurological disorders. Oxymatrine (OMT) has therapeutic effects on inflammation-mediated diseases. Whether OMT exerts therapeutic effects on WMI after ICH and the role of gut microbiota involved in this process is largely unknown.<br><br>METHODS: Neurological deficits, WMI, gut microbial composition, intestinal barrier function, and systemic inflammation were investigated after ICH. Fecal microbiota transplantation (FMT) was performed to elucidate the role of gut microbiota in the pathogenesis of ICH.<br><br>RESULTS: OMT promoted long-term neurological function recovery and ameliorated WMI in the peri-hematoma region and distal corticospinal tract (CST) region after ICH. ICH induced significant and persistent gut dysbiosis, which was obviously regulated by OMT. In addition, OMT alleviated intestinal barrier dysfunction and systemic inflammation. Correlation analysis revealed that gut microbiota alteration was significantly correlated with inflammation, intestinal barrier permeability, and neurological deficits after ICH. Moreover, OMT-induced gut microbiota alteration could confer protection against neurological deficits and intestinal barrier disruption.<br><br>CONCLUSIONS: Our study demonstrates that OMT ameliorates ICH-induced WMI and neurological deficits by modulating gut microbiota.}, }
@article {pmid36550591, year = {2023}, author = {Li, Y and Yang, L and Li, J and Gao, W and Zhao, Z and Dong, K and Duan, W and Dai, B and Guo, R}, title = {Antidepression of Xingpijieyu formula targets gut microbiota derived from depressive disorder.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {29}, number = {2}, pages = {669-681}, pmid = {36550591}, issn = {1755-5949}, mesh = {Rats ; Animals ; Depression/drug therapy ; Brain-Derived Neurotrophic Factor/metabolism ; *Gastrointestinal Microbiome ; Hypothalamo-Hypophyseal System/metabolism ; Lipopolysaccharides ; Pituitary-Adrenal System/metabolism ; Cytokines/metabolism ; *Depressive Disorder/drug therapy ; Stress, Psychological/metabolism ; }, abstract = {OBJECTIVE: This investigation aims to determine the antidepressant role of Xingpijieyu formula (XPJYF) mediated via gut microbiota (GM)-brain axis.<br><br>METHODS: We collected fecal microbiota from patients with depressive disorder (DD) and cultured microbiota in vitro. Some of microbiota were transplanted into germ-free rats with the intragastric administration of XPJYF grain at the dose of 1.533&#xa0;g/kg/day. The behaviors were studied by forced swimming test, open field test, sucrose preference test, and body weight. Products of hypothalamus-pituitary-adrenocortical (HPA) axis, neurotransmitter, and serum cytokines were investigated by enzyme linked immunosorbent assay. Glial fibrillary acidic protein (GFAP), a biomarker of astrocyte, was quantified using immunofluorescence. Microbiota culturing in vitro after XPJYF treatment was analyze by 16&#x2009;s RNA sequencing technology. We used lipopolysaccharide (LPS) to mimic activated rat primary astrocyte in vitro. Brain-derived neurotrophic factor (BDNF), cytokines, and oxidative stress factors were determined by western blotting, and glycometabolism in astrocyte was investigated by 2-deoxy-D-glucose (2-DG) uptake, adenosine triphosphate (ATP), and glucose-1-phosphate (G1P) kits.<br><br>RESULTS: Microbiota composition during 8&#xa0;mg/ml of XPJYF (H12-8) for 12&#x2009;h showed the more consistency. Lactococcus is enriched in DD-derived microbiota composition, and Biffdobacterium and Lactobacillus in H12-8 group. GLUCOSE1PMETAB-PWY and PWY-7328 of which biofunctions were dominantly encoded by Biffdobacterium were the top two of altered pathways. XPJYF improved behaviors and repressed astrocyte activation in depression rats. XPJYF elevated 2-DG uptake, ATP, glucose-1-phosphate, and brain-derived neurotrophic factor (BDNF), and inhibited cytokines and oxidative stress in LPS-induced astrocyte.<br><br>CONCLUSION: XPJYF treatment targets inflammation, activation, and glycometabolim in astrocyte via gut microbiota modulation, thereby improve animal behaviors, HPA axis dysfunction, and neurotransmitter synthesis in depression rats.}, }
@article {pmid36550389, year = {2023}, author = {Zhao, M and Jiang, G and Zhou, H and Li, J and Xiang, W and Li, S and Wang, H and Zhou, J}, title = {Gut microbiota: a potential target for improved cancer therapy.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {1}, pages = {541-552}, pmid = {36550389}, issn = {1432-1335}, support = {2020-HJXNYD-6//Joint project of Hejiang County and Southwest Medical University/ ; 2018JY0403//Science and Technology Projects of Sichuan Province/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota ; Fecal Microbiota Transplantation/methods ; Immunotherapy/methods ; Biomarkers ; *Neoplasms/therapy ; }, abstract = {Drug resistance and toxicity are major challenges observed during cancer treatment. In recent years, gut microbiota has been found to be strongly associated with the efficacy, toxicity, and side effects of chemotherapy, radiotherapy, and immunotherapy. Both preclinical studies and clinical trials have demonstrated the potential of microbiota modulation for cancer treatment. The human gut microbiota has exciting prospects for developing biomarkers to predict the outcome of cancer treatment. Moreover, multiple approaches can alter the gut microbiota composition, including faecal microbiota transplantation (FMT), probiotics, antibiotics (ATB), and diet. We describe the mechanisms by which the gut microbiota influences the efficacy and toxicity of cancer therapy, disease-related biomarkers, and methods to target the gut microbiota to improve outcomes. The purpose of this review is to provide new ideas for optimising cancer therapy by providing up-to-date information on the relationship between gut microbiota and cancer therapy, and hopes to find new targets for cancer treatment from human microbiota.}, }
@article {pmid36549470, year = {2023}, author = {Cavestro, GM and Mannucci, A and Balaguer, F and Hampel, H and Kupfer, SS and Repici, A and Sartore-Bianchi, A and Seppälä, TT and Valentini, V and Boland, CR and Brand, RE and Buffart, TE and Burke, CA and Caccialanza, R and Cannizzaro, R and Cascinu, S and Cercek, A and Crosbie, EJ and Danese, S and Dekker, E and Daca-Alvarez, M and Deni, F and Dominguez-Valentin, M and Eng, C and Goel, A and Guillem, JG and Houwen, BBSL and Kahi, C and Kalady, MF and Kastrinos, F and Kühn, F and Laghi, L and Latchford, A and Liska, D and Lynch, P and Malesci, A and Mauri, G and Meldolesi, E and Møller, P and Monahan, KJ and Möslein, G and Murphy, CC and Nass, K and Ng, K and Oliani, C and Papaleo, E and Patel, SG and Puzzono, M and Remo, A and Ricciardiello, L and Ripamonti, CI and Siena, S and Singh, SK and Stadler, ZK and Stanich, PP and Syngal, S and Turi, S and Urso, ED and Valle, L and Vanni, VS and Vilar, E and Vitellaro, M and You, YN and Yurgelun, MB and Zuppardo, RA and Stoffel, EM and ,  and ,  and , }, title = {Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {21}, number = {3}, pages = {581-603.e33}, pmid = {36549470}, issn = {1542-7714}, support = {I01 BX004455/BX/BLRD VA/United States ; I01 CX001146/CX/CSRD VA/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA220329/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Endoscopy ; Genetic Testing ; *Colorectal Neoplasms/diagnosis ; }, abstract = {BACKGROUND &amp; AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC.<br><br>METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of &#x2265;80%.<br><br>RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients.<br><br>CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.}, }
@article {pmid36548856, year = {2022}, author = {Li, K and Yang, J and Zhou, X and Wang, H and Ren, Y and Huang, Y and Liu, H and Zhong, Z and Peng, G and Zheng, C and Zhou, Z}, title = {The Mechanism of Important Components in Canine Fecal Microbiota Transplantation.}, journal = {Veterinary sciences}, volume = {9}, number = {12}, pages = {}, pmid = {36548856}, issn = {2306-7381}, support = {2022010//Science and technology program of Sichuan Medical Products Administration/ ; }, abstract = {Fecal microbiota transplantation (FMT) is a potential treatment for many intestinal diseases. In dogs, FMT has been shown to have positive regulation effects in treating Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), canine parvovirus (CPV) enteritis, acute diarrhea (AD), and acute hemorrhagic diarrhea syndrome (AHDS). FMT involves transplanting the functional components of a donor's feces into the gastrointestinal tract of the recipient. The effective components of FMT not only include commensal bacteria, but also include viruses, fungi, bacterial metabolites, and immunoglobulin A (IgA) from the donor feces. By affecting microbiota and regulating host immunity, these components can help the recipient to restore their microbial community, improve their intestinal barrier, and induce anti-inflammation in their intestines, thereby affecting the development of diseases. In addition to the above components, mucin proteins and intestinal epithelial cells (IECs) may be functional ingredients in FMT as well. In addition to the abovementioned indications, FMT is also thought to be useful in treating some other diseases in dogs. Consequently, when preparing FMT fecal material, it is important to preserve the functional components involved. Meanwhile, appropriate fecal material delivery methods should be chosen according to the mechanisms these components act by in FMT.}, }
@article {pmid36545204, year = {2022}, author = {He, G and Chen, T and Huang, L and Zhang, Y and Feng, Y and Qu, S and Yin, X and Liang, L and Yan, J and Liu, W}, title = {Tremella fuciformis polysaccharide reduces obesity in high-fat diet-fed mice by modulation of gut microbiota.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1073350}, pmid = {36545204}, issn = {1664-302X}, abstract = {Obesity is a metabolic disease associated with gut microbiota and low-grade chronic inflammation. Tremella fuciformis is a medicinal and edible fungus; polysaccharide (TP) is the main active component, which has a variety of biological activities, such as hypoglycemic and hypolipidemic. However, the anti-obesity effects and potential mechanisms of TP have never been reported. This study was conducted to elucidate the inhibitory effect of TP on high-fat diet (HFD)-induced obesity in mice. Mice were split into five groups: normal chow diet (NCD) group, NCD_TP_H group, HFD group, HFD_TP_L group and HFD_TP_H group. Our study showed that TP inhibited high-fat diet-induced weight gain and fat accumulation in mice and reduced blood glucose, hyperlipidemia and inflammation. TP also improved gut microbiota disorders by reducing the Firmicutes/Bacteroidetes ratio and modulating the relative abundance of specific gut microbiota. We also found that the anti-obesity and gut microbiota-modulating effects of TP could be transferred to HFD-fed mice via faecal microbiota transplantation (FMT), confirming that the gut microbiota was one of the targets of TP for obesity inhibition. Further studies showed that TP increased the production of short-chain fatty acids and the secretion of intestinal hormones. Our studies showed that TP inhibited obesity by modulating inflammation and the microbe-gut-brain axis, providing a rationale for developing TP to treat obesity and its complications.}, }
@article {pmid36544550, year = {2022}, author = {Li, Y and Wang, Y and Zhang, T}, title = {Fecal Microbiota Transplantation in Autism Spectrum Disorder.}, journal = {Neuropsychiatric disease and treatment}, volume = {18}, number = {}, pages = {2905-2915}, pmid = {36544550}, issn = {1176-6328}, abstract = {Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that begin in infancy. In recent years, the incidence of ASD in the world is increasing year by year. At present, the etiology and pathogenesis of ASD are not clear, and effective treatments are still lacking. In addition to neurobehavioral symptoms, children with ASD often have obvious gastrointestinal symptoms. Gut microbiota is a large microbial community in the human gut, which is closely related to the nervous system and can affect brain development and behavior through the neuroendocrine, neuroimmune and autonomic nervous systems, forming a microbiota-gut-brain axis connection. Recent studies have shown that children with ASD have significant gut microbiota and metabolic disorders, and fecal microbiota transplantation (FMT) is expected to improve ASD-related symptoms by regulating gut microbiota and metabolism. This review paper will therefore focus on FMT in the treatment of ASD, and FMT is effective in improving gastrointestinal and neurobehavioral symptoms in children with ASD.}, }
@article {pmid36544495, year = {2022}, author = {Wortelboer, K and Koopen, AM and Herrema, H and de Vos, WM and Nieuwdorp, M and Kemper, EM}, title = {From fecal microbiota transplantation toward next-generation beneficial microbes: The case of Anaerobutyricum soehngenii.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1077275}, pmid = {36544495}, issn = {2296-858X}, abstract = {The commensal gut microbiota is important for human health and well-being whereas deviations of the gut microbiota have been associated with a multitude of diseases. Restoration of a balanced and diverse microbiota by fecal microbiota transplantation (FMT) has emerged as a potential treatment strategy and promising tool to study causality of the microbiota in disease pathogenesis. However, FMT comes with logistical challenges and potential safety risks, such as the transfer of pathogenic microorganisms, undesired phenotypes or an increased risk of developing disease later in life. Therefore, a more controlled, personalized mixture of cultured beneficial microbes might prove a better alternative. Most of these beneficial microbes will be endogenous commensals to the host without a long history of safe and beneficial use and are therefore commonly referred to as next-generation probiotics (NGP) or live biotherapeutic products (LBP). Following a previous FMT study within our group, the commensal butyrate producer Anaerobutyricum spp. (previously named Eubacterium hallii) was found to be associated with improved insulin-sensitivity in subjects with the metabolic syndrome. After the preclinical testing with Anaerobutyricum soehngenii in mice models was completed, the strain was produced under controlled conditions and several clinical studies evaluating its safety and efficacy in humans were performed. Here, we describe and reflect on the development of A. soehngenii for clinical use, providing practical guidance for the development and testing of NGPs and reflecting on the current regulatory framework.}, }
@article {pmid36544282, year = {2023}, author = {Bai, X and Xu, Q and Zhang, W and Wang, C}, title = {The Gut-Eye Axis: Correlation Between the Gut Microbiota and Autoimmune Dry Eye in Individuals With Sjögren Syndrome.}, journal = {Eye &amp; contact lens}, volume = {49}, number = {1}, pages = {1-7}, doi = {10.1097/ICL.0000000000000953}, pmid = {36544282}, issn = {1542-233X}, mesh = {Humans ; *Sjogren's Syndrome/complications ; *Gastrointestinal Microbiome ; *Autoimmune Diseases/complications/therapy ; Dysbiosis/complications ; *Dry Eye Syndromes/etiology/therapy ; }, abstract = {The impact of gut microbiota on human health, autoimmunity, and disease occurrence has long been recognized since the advancement of metagenomic sequencing technology has enabled a new level of perspective on the human microbiome. Emerging findings also suggest the existence of a gut-eye axis, wherein gut dysbiosis may be a crucial factor affecting the onset and progression of multiple ocular diseases. Sjögren syndrome (SS) is a chronic autoimmune disease mainly affecting the exocrine glands, primarily the lacrimal gland in the eye, resulting in severe dry eye. Although there are currently various treatments for environmental dry eye, the efficacy for SS-related autoimmune dry eye is limited, and new and more effective therapies still need to be explored. The latest studies have demonstrated that the gut microbiota plays a key role in the pathogenesis of autoimmune dry eye. This review describes the effect of gut microbiota on the ocular surface of autoimmune dry eye; introduces the presumable pathways forming the "gut dysbiosis-ocular surface-lacrimal gland axis"; discusses the advantages of restoring intestinal microecology to treat dry eye by fecal microbiota transplantation or probiotics, which are expected to provide perspectives into the correlation between the gut microbiome and dry eye; enhance our understanding of the pathogenesis in autoimmune dry eye; and be useful in the development of future interventions of dry eye by regulating the gut microbiota.}, }
@article {pmid36543925, year = {2023}, author = {Ahn, EH and Liu, X and Alam, AM and Kang, SS and Ye, K}, title = {Helicobacter hepaticus augmentation triggers Dopaminergic degeneration and motor disorders in mice with Parkinson's disease.}, journal = {Molecular psychiatry}, volume = {28}, number = {3}, pages = {1337-1350}, pmid = {36543925}, issn = {1476-5578}, support = {AG065177//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; }, mesh = {Mice ; Humans ; Animals ; *Parkinson Disease/genetics ; alpha-Synuclein ; *Motor Disorders ; Helicobacter hepaticus ; Mice, Transgenic ; Dopamine ; Inflammation ; }, abstract = {Gut dysbiosis contributes to Parkinson's disease (PD) pathogenesis. Gastrointestinal disturbances in PD patients, along with gut leakage and intestinal inflammation, take place long before motor disorders. However, it remains unknown what bacterial species in gut microbiomes play the key role in driving PD pathogenesis. Here we show that Helicobacter hepaticus (H. hepaticus), abundant in gut microbiota from rotenone-treated human α-Synuclein gene (SNCA) transgenic mice and PD patients, initiates α-Synuclein pathology and motor deficits in an AEP-dependent manner in SNCA mice. Chronic Dextran sodium sulfate (DSS) treatment, an inflammatory inducer in the gut, activates AEP (asparagine endopeptidase) that cleaves α-Synuclein N103 and triggers its aggregation, promoting inflammation in the gut and the brain and motor defects in SNCA mice. PD fecal microbiota transplant or live H. hepaticus administration into antibiotics cocktail (Abx)-pretreated SNCA mice induces α-Synuclein pathology, inflammation in the gut and brain, and motor dysfunctions, for which AEP is indispensable. Hence, Helicobacter hepaticus enriched in PD gut microbiomes may facilitate α-Synuclein pathologies and motor impairments via activating AEP.}, }
@article {pmid36543914, year = {2022}, author = {Chioma, OS and Mallott, EK and Chapman, A and Van Amburg, JC and Wu, H and Shah-Gandhi, B and Dey, N and Kirkland, ME and Blanca Piazuelo, M and Johnson, J and Bernard, GR and Bodduluri, SR and Davison, S and Haribabu, B and Bordenstein, SR and Drake, WP}, title = {Gut microbiota modulates lung fibrosis severity following acute lung injury in mice.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {1401}, pmid = {36543914}, issn = {2399-3642}, support = {P20GM125504/GM/NIGMS NIH HHS/United States ; P20 GM125504/GM/NIGMS NIH HHS/United States ; T32AR059039-10/AR/NIAMS NIH HHS/United States ; K24 HL127301/HL/NHLBI NIH HHS/United States ; K12 HL 143956-4/HL/NHLBI NIH HHS/United States ; T32 AR059039/AR/NIAMS NIH HHS/United States ; R56 HL149129/HL/NHLBI NIH HHS/United States ; 1R56HL149129-01A1/HL/NHLBI NIH HHS/United States ; K12 HL143956/HL/NHLBI NIH HHS/United States ; K24 HL127301-01/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Acute Lung Injury ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Interleukin-17 ; Mice, Inbred C57BL ; *Pulmonary Fibrosis/metabolism/pathology ; Fibroblasts/metabolism/microbiology ; }, abstract = {Independent studies demonstrate the significance of gut microbiota on the pathogenesis of chronic lung diseases; yet little is known regarding the role of the gut microbiota in lung fibrosis progression. Here we show, using the bleomycin murine model to quantify lung fibrosis in C57BL/6 J mice housed in germ-free, animal biosafety level 1 (ABSL-1), or animal biosafety level 2 (ABSL-2) environments, that germ-free mice are protected from lung fibrosis, while ABSL-1 and ABSL-2 mice develop mild and severe lung fibrosis, respectively. Metagenomic analysis reveals no notable distinctions between ABSL-1 and ABSL-2 lung microbiota, whereas greater microbial diversity, with increased Bifidobacterium and Lactobacilli, is present in ABSL-1 compared to ABSL-2 gut microbiota. Flow cytometric analysis reveals enhanced IL-6/STAT3/IL-17A signaling in pulmonary CD4 + T cells of ABSL-2 mice. Fecal transplantation of ABSL-2 stool into germ-free mice recapitulated more severe fibrosis than transplantation of ABSL-1 stool. Lactobacilli supernatant reduces collagen 1 A production in IL-17A- and TGFβ1-stimulated human lung fibroblasts. These findings support a functional role of the gut microbiota in augmenting lung fibrosis severity.}, }
@article {pmid36542917, year = {2023}, author = {Wu, Z and Tian, E and Chen, Y and Dong, Z and Peng, Q}, title = {Gut microbiota and its roles in the pathogenesis and therapy of endocrine system diseases.}, journal = {Microbiological research}, volume = {268}, number = {}, pages = {127291}, doi = {10.1016/j.micres.2022.127291}, pmid = {36542917}, issn = {1618-0623}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Gastrointestinal Diseases/therapy ; *Endocrine System Diseases/therapy ; }, abstract = {A new field of microbial research is the relationship between microorganisms and multicellular hosts. It is known that gut microbes can cause various endocrine system diseases, such as diabetes and thyroid disease. Changes in the composition or structure and the metabolites of gut microbes may cause gastrointestinal disorders, including ulcers or intestinal perforation and other inflammatory and autoimmune diseases. In recent years, reports on the interactions between intestinal microorganisms and endocrine system diseases have been increasingly documented. In the meantime, the treatment based on gut microbiome has also been paid much attention. For example, fecal microbiota transplantation is found to have a therapeutic effect on many diseases. As such, understanding the gut microbiota-endocrine system interactions is of great significance for the theranostic of endocrine system diseases. Herein, we summarize the relations of gut microbiome with endocrine system diseases, and discuss the potentials of regulating gut microbiome in treating those diseases. In addition, the concerns and possible solutions regarding the gut microbiome-based therapy are discussed.}, }
@article {pmid36537602, year = {2023}, author = {Santacroce, L and Di Domenico, M and Montagnani, M and Jirillo, E}, title = {Antibiotic Resistance and Microbiota Response.}, journal = {Current pharmaceutical design}, volume = {29}, number = {5}, pages = {356-364}, doi = {10.2174/1381612829666221219093450}, pmid = {36537602}, issn = {1873-4286}, mesh = {Animals ; Humans ; *Microbiota ; *Probiotics/therapeutic use ; Prebiotics ; Drug Resistance, Microbial ; *Gastrointestinal Microbiome ; Anti-Bacterial Agents/pharmacology/therapeutic use ; }, abstract = {Use of antibiotics has dramatically eradicated bacterial infections in humans and animals. However, antibiotic overdose and abuse are responsible for the emergence of so-called multi-drug resistant bacteria. Gut microbiota deserves many functions in the host, and among them, integrity of epithelial barrier and enhancement of protective immune responses are included. There is evidence that antibiotic treatment decreases the diversity of gut microbiota species, also provoking metabolic changes, increased susceptibility to colonization and decrease of antimicrobial peptide secretion, leading to antibiotic resistance. In this review, the major mechanisms involved in antibiotic resistance will be illustrated. However, novel findings on the potential use of alternative treatments to overcome antibiotic resistance will be elucidated. In this regard, special emphasis will be placed on microcins, prebiotics, probiotics and postbiotics, as well as phage therapy and fecal microbial transplantation.}, }
@article {pmid36537331, year = {2024}, author = {Wang, S and Cui, J and Jiang, S and Zheng, C and Zhao, J and Zhang, H and Zhai, Q}, title = {Early life gut microbiota: Consequences for health and opportunities for prevention.}, journal = {Critical reviews in food science and nutrition}, volume = {64}, number = {17}, pages = {5793-5817}, doi = {10.1080/10408398.2022.2158451}, pmid = {36537331}, issn = {1549-7852}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Probiotics ; *Prebiotics ; Fecal Microbiota Transplantation ; Infant ; Animals ; Diet ; Enterocolitis, Necrotizing/prevention &amp; control/microbiology ; Celiac Disease/prevention &amp; control/microbiology ; Obesity/prevention &amp; control/microbiology ; Hypersensitivity/prevention &amp; control ; Autism Spectrum Disorder/prevention &amp; control/microbiology ; Asthma/prevention &amp; control/microbiology ; }, abstract = {The gut microbiota influences many aspects of the host, including immune system maturation, nutrient absorption and metabolism, and protection from pathogens. Increasing evidences from cohort and animal studies indicate that changes in the gut microbiota early in life increases the risk of developing specific diseases early and later in life. Therefore, it is becoming increasingly important to identify specific disease prevention or therapeutic solutions targeting the gut microbiota, especially during infancy, which is the window of the human gut microbiota establishment process. In this review, we provide an overview of current knowledge concerning the relationship between disturbances in the gut microbiota early in life and health consequences later in life (e.g., necrotizing enterocolitis, celiac disease, asthma, allergies, autism spectrum disorders, overweight/obesity, diabetes and growth retardation), with a focus on changes in the gut microbiota prior to disease onset. In addition, we summarize and discuss potential microbiota-based interventions early in life (e.g., diet adjustments, probiotics, prebiotics, fecal microbiota transplantation, environmental changes) to promote health or prevent the development of specific diseases. This knowledge should aid the understanding of early life microbiology and inform the development of prediction and prevention measures for short- and long-term health disorders based on the gut microbiota.}, }
@article {pmid36537141, year = {2023}, author = {Nie, C and Xie, X and Liu, H and Yuan, X and Ma, Q and Tu, A and Zhang, M and Chen, Z and Li, J}, title = {Galactooligosaccharides ameliorate dietary advanced glycation end product-induced intestinal barrier damage in C57BL/6 mice by modulation of the intestinal microbiome.}, journal = {Food &amp; function}, volume = {14}, number = {2}, pages = {845-856}, doi = {10.1039/d2fo02959f}, pmid = {36537141}, issn = {2042-650X}, mesh = {Animals ; Mice ; *Dietary Advanced Glycation End Products ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Oligosaccharides/pharmacology ; Mice, Inbred C57BL ; }, abstract = {Advanced glycation end products (AGEs) are increasingly recognized as potentially pathogenic components of processed foods, and long-term consumption of dietary AGEs triggers disruption of the intestinal barrier integrity and increases the risk of chronic diseases. Galactooligosaccharides (GOS) as prebiotics can modulate the intestinal microbiota and improve the intestinal barrier integrity. In this study, we aimed to investigate whether GOS could ameliorate the intestinal barrier damage induced by AGEs. The results showed an increased number of goblet cells (AGEs vs. H-GOS, 133.4 vs. 174.7, p < 0.05) and neutral mucin area (PAS positive area, 7.29% vs. 10.05%, p < 0.05). Upregulated expressions of occludin and claudin-1 and improved intestinal barrier integrity were observed in the H-GOS group. Using 16S rRNA sequencing analysis, we found that GOS significantly reduced the high enrichment of Akkermansia (16.95% vs. 1.29%, p < 0.05) induced by dietary AGEs while increasing the content of short-chain fatty acids. Fecal microbiota transplantation (FMT) showed that AGE-induced damage to the intestinal mucus barrier was reversed in the H-GOS transplanted group. Collectively, GOS ameliorated dietary AGE-induced intestinal barrier damage by reversing the dysregulated state of the intestinal microbiota. Our study lays the foundation for further research on dietary guidelines for populations with high AGE diets.}, }
@article {pmid36536532, year = {2023}, author = {Bloom, PP and Young, VB}, title = {Microbiome therapeutics for the treatment of recurrent Clostridioides difficile infection.}, journal = {Expert opinion on biological therapy}, volume = {23}, number = {1}, pages = {89-101}, doi = {10.1080/14712598.2022.2154600}, pmid = {36536532}, issn = {1744-7682}, mesh = {Humans ; *Clostridioides difficile ; Fecal Microbiota Transplantation/adverse effects ; *Clostridium Infections/drug therapy ; *Microbiota ; Anti-Bacterial Agents/adverse effects ; Treatment Outcome ; Recurrence ; }, abstract = {INTRODUCTION: The gut microbiome is implicated in Clostridioides difficile infection (CDI) and recurrent CDI (rCDI).<br><br>AREAS COVERED: This review covers the mechanisms by which microbiome therapeutics treat rCDI, their efficacy and safety, and clinical trial design considerations for future research.<br><br>EXPERT OPINION: Altering the chemical environment of the gut and reconstituting colonization resistance is a promising strategy for preventing and treating rCDI. Fecal microbiota transplant (FMT) is safe and effective for the treatment of rCDI. However, limitations of FMT have prompted investigation into alternative microbiome therapeutics. These alternative microbiome therapies require further evaluation, and adaptive trial designs should be strongly considered to more rapidly discern variables including the need for bowel preparation, timing and selection of pre-treatment antibiotics, and dose and duration of microbiome therapeutics. A broad range of adverse events must be prospectively evaluated in these controlled trials, as microbiome therapeutics have the potential for numerous effects. Future studies will lead to a greater understanding of the mechanisms by which microbiome therapies can break the cycle of rCDI, which should ultimately yield a personalized approach to rCDI treatment that restores an individual's specific deficit(s) in colonization resistance to C. difficile.}, }
@article {pmid36535571, year = {2023}, author = {Yan, M and Man, S and Liang, Y and Ma, L and Guo, L and Huang, L and Gao, W}, title = {Diosgenin alleviates nonalcoholic steatohepatitis through affecting liver-gut circulation.}, journal = {Pharmacological research}, volume = {187}, number = {}, pages = {106621}, doi = {10.1016/j.phrs.2022.106621}, pmid = {36535571}, issn = {1096-1186}, mesh = {Animals ; Mice ; Choline/pharmacology ; Disease Models, Animal ; Liver ; Methionine/metabolism/pharmacology ; Mice, Inbred C57BL ; *Non-alcoholic Fatty Liver Disease/metabolism ; Intestines/metabolism ; }, abstract = {Nonalcoholic steatohepatitis (NASH), as the aggressive form of nonalcoholic fatty liver disease (NAFLD), rapidly becomes the leading cause of end-stage liver disease or liver transplantation. Nowadays, there has no approved drug for NASH treatment. Diosgenin possesses multiple beneficial effects towards inhibition of lipid accumulation, cholesterol metabolism, fibrotic progression and inflammatory response. However, there has been no report concerning its effects on NASH so far. Using methionine and choline-deficient (MCD) feeding mice, we evaluated the anti-NASH effects of diosgenin. 16 S rDNA was used to investigate gut microbiota composition. Transcriptome sequencing, LC/MS and GC/MS analysis were used to evaluate bile acids (BAs) metabolism and their related pathway. Compared with the MCD group, diosgenin treatment improved the hepatic dysfunction, especially decreased the serum and hepatic TC, TG, ALT, AST and TBA to nearly 50%. Content of BAs, especially CA and TCA, were decreased from 59.30 and 26.00-39.71 and 11.48 ng/mg in liver and from 0.96 and 2.1-0.47 and 1.13 μg/mL in serum, and increased from 7.01 and 11.08-3.278 and 5.11 ng/mg in feces, respectively. Antibiotic and fecal microbiota transplantation (FMT) treatment further confirmed the therapeutic effect of diosgenin on gut microbiota, especially Clostridia (LDA score of 4.94), which regulated BAs metabolism through the hepatic FXR-SHP and intestinal FXR-FGF15 pathways. These data indicate that diosgenin prevents NASH by altering Clostridia and BAs metabolism. Our results shed light on the mechanisms of diosgenin in treating NASH, which pave way for the design of novel clinical therapeutic strategies.}, }
@article {pmid36535435, year = {2023}, author = {Zhang, L and Zhang, Y and Jiang, X and Mao, L and Xia, Y and Fan, Y and Li, N and Jiang, Z and Qin, X and Jiang, Y and Liu, G and Qiu, F and Zhang, J and Zou, Z and Chen, C}, title = {Disruption of the lung-gut-brain axis is responsible for cortex damage induced by pulmonary exposure to zinc oxide nanoparticles.}, journal = {Toxicology}, volume = {485}, number = {}, pages = {153390}, doi = {10.1016/j.tox.2022.153390}, pmid = {36535435}, issn = {1879-3185}, mesh = {Mice ; Animals ; *Zinc Oxide/toxicity ; Brain-Gut Axis ; Mice, Inbred C57BL ; Lung ; *Nanoparticles/toxicity ; Cerebral Cortex ; }, abstract = {Increasing evidence shows that gut microbiota is important for host health in response to metal nanomaterials exposure. However, the effect of gut microbiota on the cortex damage caused by pulmonary exposure to zinc oxide nanoparticles (ZnONPs) remains mainly unknown. In this study, a total of 48 adult C57BL/6J mice were intratracheally instilled with 0.6 mg/kg ZnONPs in the presence or absence of antibiotics (ABX) treatment. Besides, 24 mice were treated with or without fecal microbiota transplantation (FMT) after the intraperitoneal administration of ABX. Our results demonstrated for the first time that dysbiosis induced by ABX treatment significantly aggravated cortex damage induced by pulmonary exposure to ZnONPs. Such damage might highly occur through the induction of oxidative stress, manifested by the enhancement of antioxidative enzymes and products of lipid peroxidation. However, ferroptosis was not involved in this process. Interestingly, our data revealed that ABX treatment exacerbated the alterations of gut-brain peptides (including Sst, Sstr2, and Htr4) induced by ZnONPs in both gut and cortex tissues. Moreover, fecal microbiota transplantation (FMT) was able to alleviate cerebral cortex damage, oxidative stress, and alterations of gut-brain peptides induced by pulmonary exposure to ZnONPs. The results together indicate that pulmonary exposure to ZnONPs causes cerebral cortex damage possibly via the disruption of the lung-gut-brain axis. These findings not only propose valuable insights into the mechanism of ZnONPs neurotoxicity but also provide a potential therapeutic method against brain disorders induced by pulmonary exposure to ZnONPs. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the current study are available from the The corresponding author on reasonable request.}, }
@article {pmid36532458, year = {2022}, author = {Zhou, Y and Zhou, C and Zhang, A}, title = {Gut microbiota in acute leukemia: Current evidence and future directions.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1045497}, pmid = {36532458}, issn = {1664-302X}, abstract = {Gut microbiota includes a large number of microorganisms inhabiting the human gastrointestinal tract, which show a wide range of physiological functions, including digestion, metabolism, immunity, neural development, etc., and are considered to play an increasingly important role in health and disease. A large number of studies have shown that gut microbiota are closely associated with the onset and development of several diseases. In particular, the interaction between gut microbiota and cancer has recently attracted scholars' attention. Acute leukemia (AL) is a common hematologic malignancy, especially in children. Microbiota can affect hematopoietic function, and the effects of chemotherapy and immunotherapy on AL are noteworthy. The composition and diversity of gut microbiota are important factors that influence and predict the complications and prognosis of AL after chemotherapy or hematopoietic stem cell transplantation. Probiotics, prebiotics, fecal microbiota transplantation, and dietary regulation may reduce side effects of leukemia therapy, improve response to treatment, and improve prognosis. This review concentrated on the role of the gut microbiota in the onset and development of AL, the response and side effects of chemotherapy drugs, infection during treatment, and therapeutic efficacy. According to the characteristics of gut microbes, the applications and prospects of microbial preparations were discussed.}, }
@article {pmid36532422, year = {2022}, author = {Liu, X and Zhang, M and Wang, X and Liu, P and Wang, L and Li, Y and Wang, X and Ren, F}, title = {Fecal microbiota transplantation restores normal fecal composition and delays malignant development of mild chronic kidney disease in rats.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1037257}, pmid = {36532422}, issn = {1664-302X}, abstract = {Chronic kidney disease (CKD) is associated with gut microbiome dysbiosis, but the role of intestinal flora in CKD treatment remains to be elucidated. Fecal microbiota transplantation (FMT) can be utilized to re-establish healthy gut microbiota for a variety of diseases, which offers new insight for treating CKD. First, 5/6 nephrectomy rats (Donor CKD) and sham rats (Donor Sham) were used as donors for FMT, and fecal metagenome were analyzed to explore potential therapeutic targets. Then, to assess the effect of FMT on CKD, sterilized 1/2 nephrectomy rats were transplanted with fecal microbiota from Donor sham (CKD/Sham) or Donor CKD (CKD/CKD) rats, and 1/2 nephrectomy rats without FMT (CKD) or no nephrectomy (Sham) were used as model control or normal control. Results showed that Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 were enriched in Donor CKD, while Lactobacillus johnsonii and Lactobacillus intestinalis were reduced. In addition, the increased abundance of microbial functions included tryptophan metabolism and lysine degradation contributing to the accumulation of protein-bound uremic toxins (PBUTs) in Donor CKD. Genome analysis indicated that FMT successfully differentiated groups of gut microbes and altered specific gut microbiota after 1 week of treatment, with Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 increasing in CKD/CKD group as well as Lactobacillus johnsonii and Lactobacillus intestinalis being improved in CKD/Sham group. In comparison to CKD group, substantial PBUT buildup and renal damage were observed in CKD/CKD. Interestingly, compared to CKD or CKD/CKD group, tryptophan metabolism and lysine degradation were efficiently suppressed in CKD/Sham group, while lysine biosynthesis was promoted. Therefore, FMT considerably reduced PBUTs accumulation. After FMT, PBUTs and renal function in CKD/Sham rats remained the same as in Sham group throughout the experimental period. In summary, FMT could delay the malignant development of CKD by modifying microbial amino acid metabolism through altering the microenvironment of intestinal flora, thereby providing a novel potential approach for treating CKD.}, }
@article {pmid36532416, year = {2022}, author = {Li, H and Li, N and Lu, Q and Yang, J and Zhao, J and Zhu, Q and Yi, S and Fu, W and Luo, T and Tang, J and Zhang, Y and Yang, G and Liu, Z and Xu, J and Chen, W and Zhu, J}, title = {Chronic alcohol-induced dysbiosis of the gut microbiota and gut metabolites impairs sperm quality in mice.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1042923}, pmid = {36532416}, issn = {1664-302X}, abstract = {Studies have indicated that the ethanol exposure impairs the gut microbiota, At the same time, high levels of alcohol exposure damage sperm in mice. However, whether the gut microbiota is involved in mediating the effects of alcohol on sperm quality remains unclear. This study aimed to assess the effect of chronic alcohol consumption on intestinal microbiota in mice and analyze the potential pathophysiological effect of altered intestinal microbiota on sperm quality. We established a mouse model of chronic alcohol consumption by allowing male C57 mice to freely ingest 10% ethanol for 10 weeks, and collected the fecal microbiota of the male mice in the chronic drinking group (alcohol) and the control group (control) and transplanted the specimens into the transplant groups (the alcohol-fecal microbiota transplantation [FMT] group and the control-FMT group). Sperm quality was significantly decreased in the alcohol-FMT group compared with the control-FMT group. Gut microbiota analysis revealed that the abundance of 11 operational taxonomic units (OTUs) was altered in the alcohol-FMT group. Nontargeted metabolomics identified 105 differentially altered metabolites, which were mainly annotated to amino acids, lipids, glycerophosphoethanolamine, organic oxygenic compounds, organic acids and their derivatives, steroids, and flavonoids. In particular, the oxidative phosphorylation pathway, which is the key to spermatogenesis, was significantly enriched in the alcohol-FMT group. Moreover, compared with the control-FMT group, the alcohol-FMT group presented significantly higher serum endotoxin and inflammatory cytokine levels, with more pronounced T cell and macrophage infiltration in the intestinal lamina propria and elevated levels of testicular inflammatory cytokines. In addition, RNA sequencing showed significant differences in the expression of testis-related genes between the alcohol-FMT group and the control-FMT group. In particular, the expression of genes involved in gamete meiosis, testicular mitochondrial function, and the cell division cycle was significantly reduced in alcohol-FMT mice. In conclusion, these findings indicated that intestinal dysbiosis induced by chronic alcohol consumption may be an important factor contributing to impaired sperm quality. Chronic alcohol consumption induces intestinal dysbiosis, which then leads to metabolic disorders, elevated serum endotoxin and inflammatory cytokine levels, testicular inflammation, abnormal expression of related genes, and ultimately, impaired sperm quality. These findings are potentially useful for the treatment of male infertility.}, }
@article {pmid36532026, year = {2022}, author = {Kang, Y and Ren, P and Kuang, X and Li, L and Kang, X and Yang, Y}, title = {Editorial: Improve metabolic and autoimmune diseases by regulating gut microbiota.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1091805}, doi = {10.3389/fimmu.2022.1091805}, pmid = {36532026}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Autoimmune Diseases/therapy ; }, }
@article {pmid36530877, year = {2022}, author = {Zhang, X and Ishikawa, D and Ohkusa, T and Fukuda, S and Nagahara, A}, title = {Hot topics on fecal microbiota transplantation for the treatment of inflammatory bowel disease.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1068567}, pmid = {36530877}, issn = {2296-858X}, abstract = {Inflammatory bowel disease (IBD) is a chronic intestinal mucosal inflammatory disease with complex etiology. Traditional anti-inflammatory treatment regimens have yielded unsatisfactory results. As research continues to deepen, it has been found that the gut microbiota of patients with IBD is generally altered. The presence of microorganisms in the human gastrointestinal tract is inextricably linked to the regulation of health and disease. Disruption of the microbiotic balance of microbiota in the gastrointestinal tract is called dysbiosis, which leads to disease. Therefore, in recent years, the exploration of therapeutic methods to restore the homeostasis of the gut microbiota has attracted attention. Moreover, the use of the well-established fecal microbiota transplantation (FMT) regimen for the treatment of Clostridioides difficile infection has attracted the interest of IBD researchers. Therefore, there are an increasing number of clinical studies regarding FMT for IBD treatment. However, a series of questions regarding FMT in the treatment of IBD warrants further investigation and discussion. By reviewing published studies, this review explored hot topics such as the efficacy, safety, and administration protocol flow of FMT in the treatment of IBD. Different administration protocols have generally shown reassuring results with significant efficacy and safety. However, the FMT treatment regimen needs to be further optimized. We believe that in the future, individual customized or standard FMT implementation will further enhance the relevance of FMT in the treatment of IBD.}, }
@article {pmid36530444, year = {2022}, author = {Zhang, S and Deng, F and Chen, J and Chen, F and Wu, Z and Li, L and Hou, K}, title = {Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes: A systematic review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1075201}, pmid = {36530444}, issn = {2235-2988}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Diabetes Mellitus, Type 1/therapy ; *Gastrointestinal Microbiome ; Feces ; Intestines ; }, abstract = {There is a strong link between fecal microbiota and the development of type 1 diabetes. As an emerging therapeutic modality, fecal microbiota transplantation has been shown to be safe and effective in the treatment of many intestinal and extraintestinal diseases. Various studies have found that fecal microbiota transplantation can treat diseases by correcting patients' immune disorders. Besides, many studies have found that fecal microbiota transplantation can improve glycemic control and insulin resistance in diabetic patients. Therefore, this paper reviews the mechanism of action of fecal microbiota transplantation on autoimmune-mediated T1DM and the current research progress, feasibility, and issues that need to be addressed in the future development of fecal microbiota transplantation in the treatment of autoimmune-mediated T1DM.}, }
@article {pmid36529248, year = {2023}, author = {Li, B and Xu, M and Wang, Y and Feng, L and Xing, H and Zhang, K}, title = {Gut microbiota: A new target for traditional Chinese medicine in the treatment of depression.}, journal = {Journal of ethnopharmacology}, volume = {303}, number = {}, pages = {116038}, doi = {10.1016/j.jep.2022.116038}, pmid = {36529248}, issn = {1872-7573}, mesh = {Humans ; Bacteria ; *Drugs, Chinese Herbal/pharmacology/therapeutic use/chemistry ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Medicine, Chinese Traditional ; }, abstract = {The causes of depression are complex. Many factors are involved in its pathogenesis, including the individual's biological and social environment. Although numerous studies have reported that the gut microbiota plays a significant role in depression, drugs that regulate the gut microbiota to treat depression have not yet been comprehensively reviewed. At the same time, more and more attention has been paid to the characteristics of traditional Chinese medicine (TCM) in improving depression by regulating gut microbiota. In ancient times, fecal microbiota transplantation was recorded in TCM for the treatment of severe diseases. There are also records in Chinese ancient books about the use of TCM to adjust gut microbiota to treat diseases, which has opened up a unique research field in TCM. Therefore, this article focuses on the pharmacological effects, targets, and mechanisms of TCM in improving depression by mediating the influence of gut microbiota.<br><br>AIM OF THIS REVIEW: To summarize the role the gut microbiota plays in depression, highlight potential regulatory targets, and elucidate the anti-depression mechanisms of TCMs through regulation of the gut microbiota.<br><br>METHODS: A systematic review of 256 clinical trials and pharmaceutical studies published until June 2022 was conducted in eight electronic databases (Web of Science, PubMed, SciFinder, Research Gate, ScienceDirect, Google Scholar, Scopus, and China Knowledge Infrastructure), according to the implemented PRISMA criteria, using the search terms "traditional Chinese medicine," "depression," and "gut microbiota."<br><br>RESULTS: Numerous studies reported the effects of different gut bacteria on depression and that antidepressants work through the gut microbiota. TCM preparations based on compound Chinese medicine, the Chinese Materia Medica, and major bioactive components exerted antidepressant-like effects by improving levels of neurotransmitters, short-chain fatty acids, brain-derived neurotrophic factor, kynurenine, and cytokines via regulation of the gut microbiota.<br><br>CONCLUSION: This review summarized the anti-depression effects of TCM on the gut microbiota, providing evidence that TCMs are safe and effective in the treatment of depression and may provide a new therapeutic approach.}, }
@article {pmid36527519, year = {2022}, author = {Yousefi, B and Babaeizad, A and Banihashemian, SZ and Feyzabadi, ZK and Dadashpour, M and Pahlevan, D and Ghaffari, H and Eslami, M}, title = {Gastrointestinal Tract, Microbiota and Multiple Sclerosis (MS) and the Link Between Gut Microbiota and CNS.}, journal = {Current microbiology}, volume = {80}, number = {1}, pages = {38}, pmid = {36527519}, issn = {1432-0991}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Multiple Sclerosis ; Fatty Acids, Volatile ; *Microbiota ; Gastrointestinal Tract ; Central Nervous System ; }, abstract = {Multiple sclerosis (MS) is a chronic inflammatory disease characterized by central nervous system (CNS) lesions that can lead to severe neurological defects. Evidence is mounting that immune function is crucial in neuroinflammatory illnesses like MS. Through its impact on systemic immunological reactions, the large microbial population known as the gut microbiota has been linked to both human health and disease. The gut-brain axis (GBA) therefore encompasses neurological, immunological, and hormonal pathways, and microbiota can have a number of effects on the immune system, influencing MS. Recent research revealed a bidirectional relationship between metabolites originating from the gut microbiota, namely short-chain fatty acids (SCFAs). Intestinal epithelial cells are influenced by SCFAs, which also boosts the secretion of -Defensins and regenerating islet-derived III (REGIII) proteins. These proteins reduce intestinal pathogens, induce T-reg differentiation, and modulate immune responses by reducing IL-1 and IL-6 expression and increasing IL-10. Nutrition and psychological stress are two of the most significant elements that can directly and indirectly change the microbiota compositions along with other environmental influencing factors. An important regulator of intestinal physiology in the gut-brain-microbiota axis is butyrate, a well-known SCFA. Intestinal dysbiosis, altered intestinal barrier function, behavioral abnormalities, and activation of the hypothalamic-pituitary-adrenal (HPA) axis are all brought on by exposure. Probiotics, bacterial metabolite supplementation, fecal matter transplantation, defined microbial communities, and dietary intervention are some methods for modifying the composition of the gut microbiota that may be used to affect disease-related immune dysfunction and serve as the foundation for a new class of therapeutics.}, }
@article {pmid36525272, year = {2022}, author = {Lahtinen, P and Juuti, A and Luostarinen, M and Niskanen, L and Liukkonen, T and Tillonen, J and Kössi, J and Ilvesmäki, V and Viljakka, M and Satokari, R and Arkkila, P}, title = {Effectiveness of Fecal Microbiota Transplantation for Weight Loss in Patients With Obesity Undergoing Bariatric Surgery: A Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {5}, number = {12}, pages = {e2247226}, pmid = {36525272}, issn = {2574-3805}, mesh = {Female ; Humans ; *Obesity, Morbid/surgery ; Fecal Microbiota Transplantation ; Weight Loss ; *Bariatric Surgery ; Obesity/surgery ; }, abstract = {IMPORTANCE: Severe obesity is a major health concern. However, a few patients remain resistant to bariatric surgery and other treatments. Animal studies suggest that weight may be altered by fecal microbiota transplantation (FMT) from a lean donor.<br><br>OBJECTIVE: To determine whether FMT from a lean donor reduces body weight and further improves the results of bariatric surgery.<br><br>This double-blinded, placebo-controlled, multicenter, randomized clinical trial was conducted in 2018 to 2021 among adult individuals with severe obesity treated at 2 bariatric surgery centers in Finland and included 18 months of follow-up. Patients eligible for bariatric surgery were recruited for the study. Data were analyzed from March 2021 to May 2022.<br><br>INTERVENTIONS: FMT from a lean donor or from the patient (autologous placebo) was administered by gastroscopy into the duodenum. Bariatric surgery was performed 6 months after the baseline intervention using laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG).<br><br>MAIN OUTCOMES AND MEASURES: The main outcome was weight reduction measured as the percentage of total weight loss (TWL).<br><br>RESULTS: Forty-one patients were recruited to participate in the study and were included in the final analysis (29 women [71.1%]; mean [SD] age, 48.7 [8.7] years; mean [SD] body mass index, 42.5 [6.0]). A total of 21 patients received FMT from a lean donor, and 20 received an autologous placebo. Six months after FMT, 34 patients underwent LRYGB and 4 underwent LSG. Thirty-four patients (82.9%) attended the last visit 18 months after the baseline visit. The percentage of TWL at 6 months was 4.8% (95% CI, 2.7% to 7.0%; P&#x2009;<&#x2009;.001) in the FMT group and 4.6% (95% CI, 1.5% to 7.6%; P&#x2009;=&#x2009;.006) in the placebo group, but no difference was observed between the groups. At 18 months from the baseline (ie, 12 months after surgery), the percentage of TWL was 25.3% (95% CI, 19.5 to 31.1; P&#x2009;<&#x2009;.001) in the FMT group and 25.2% (95% CI, 20.2 to 30.3; P&#x2009;<&#x2009;.001) in the placebo group; however, no difference was observed between the groups.<br><br>CONCLUSIONS AND RELEVANCE: FMT did not affect presurgical and postsurgical weight loss. Further studies are needed to elucidate the possible role of FMT in obesity.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03391817.}, }
@article {pmid36522083, year = {2023}, author = {Sun, B and Liu, M and Tang, L and Zhou, X and Hu, C and Chen, L}, title = {Variability in fecal metabolome depending on age, PFBS pollutant, and fecal transplantation in zebrafish: A non-invasive diagnosis of health.}, journal = {Journal of environmental sciences (China)}, volume = {127}, number = {}, pages = {530-540}, doi = {10.1016/j.jes.2022.06.019}, pmid = {36522083}, issn = {1001-0742}, mesh = {Animals ; *Zebrafish ; Fecal Microbiota Transplantation ; *Environmental Pollutants/analysis ; Metabolome ; Feces ; Metabolomics ; Hormones/analysis ; }, abstract = {To protect the wellbeing of research animals, certain non-invasive measures are in increasing need to facilitate an early diagnosis of health and toxicity. In this study, feces specimen was collected from adult zebrafish to profile the metabolome fingerprint. Variability in fecal metabolite composition was also distinguished as a result of aging, perfluorobutanesulfonate (PFBS) toxicant, and fecal transplantation. The results showed that zebrafish feces was very rich in a diversity of metabolites that belonged to several major classes, including lipid, amino acid, carbohydrate, vitamin, steroid hormone, and neurotransmitter. Fecal metabolites had functional implications to multiple physiological activities, which were characterized by the enrichment of digestion, absorption, endocrine, and neurotransmission processes. The high richness and functional involvement of fecal metabolites pinpointed feces as an abundant source of diagnostic markers. By comparison between young and aged zebrafish, fundamental modifications of fecal metabolomes were caused by aging progression, centering on the neuroactive ligand-receptor interaction pathway. Exposure of aged zebrafish to PFBS pollutant also significantly disrupted the metabolomic structure in feces. Of special concern were the changes in fecal hormone intermediates after PFBS exposure, which was concordant with the in vivo endocrine disrupting effects of PFBS. Furthermore, it was intriguing that transplantation of young zebrafish feces efficiently mitigated the metabolic perturbation of PFBS in aged recipients, highlighting the health benefits of therapeutic strategies based on gut microbiota manipulation. In summary, the present study provides preliminary clues to evidence the non-invasive advantage of fecal metabolomics in the early diagnosis and prediction of physiology and toxicology.}, }
@article {pmid36520071, year = {2023}, author = {Man, S and Xie, L and Liu, X and Wang, G and Liu, C and Gao, W}, title = {Diosgenin relieves oxaliplatin-induced pain by affecting TLR4/NF-κB inflammatory signaling and the gut microbiota.}, journal = {Food &amp; function}, volume = {14}, number = {1}, pages = {516-524}, doi = {10.1039/d2fo02877h}, pmid = {36520071}, issn = {2042-650X}, mesh = {Animals ; Mice ; Rats ; *Diosgenin/pharmacology ; *Gastrointestinal Microbiome ; *Neuralgia/drug therapy ; NF-kappa B/genetics/metabolism ; Oxaliplatin ; Toll-Like Receptor 4/genetics/metabolism ; }, abstract = {Diosgenin extracted from fenugreek, yam and other foods exhibits a wide range of pharmacological activities, especially for the treatment of pain and other nervous system diseases. However, its role in oxaliplatin-induced peripheral neuropathy (OIPN) is unclear. To explore its detailed mechanism on the pain caused by chemotherapy, we carried out this experiment. In this study, the effects of diosgenin on injured PC12 cells and OIPN mice were examined. The results showed that diosgenin not only protected PC12 from injury, but also reduced the mechanical withdrawal threshold and cold hyperalgesia in OIPN mice. Diosgenin inhibited oxidative stress, the cell glial fibrillary acidic protein, and the pro-inflammatory cytokines such as tumor necrosis factor-α, toll-like receptor 4 and nuclear factor-κB in the brain. Furthermore, the fecal microbiota transplantation experiment indicated that diosgenin improved OIPN through regulation of the gut microbiota. All in all, diosgenin ameliorates peripheral neuropathy and is worthy of further study in the treatment of neuropathic pain.}, }
@article {pmid36519447, year = {2022}, author = {Wei, S and Bahl, MI and Baunwall, SMD and Dahlerup, JF and Hvas, CL and Licht, TR}, title = {Gut microbiota differs between treatment outcomes early after fecal microbiota transplantation against recurrent Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2084306}, pmid = {36519447}, issn = {1949-0984}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Clostridioides difficile/physiology ; Vancomycin/therapeutic use ; *Clostridium Infections/therapy ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {AbstarctIn fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (CDI), clinical outcomes are usually determined after 8 weeks. We hypothesized that the intestinal microbiota changes earlier than this timepoint, and analyzed fecal samples obtained 1 week after treatment from 64 patients diagnosed with recurrent CDI and included in a randomized clinical trial, where the infection was treated with either vancomycin-preceded FMT (N = 24), vancomycin (N = 16) or fidaxomicin (N = 24). In comparison with non-responders, patients with sustained resolution after FMT had increased microbial alpha diversity, enrichment of Ruminococcaceae and Lachnospiraceae, depletion of Enterobacteriaceae, more pronounced donor microbiota engraftment, and resolution of gut microbiota dysbiosis. We found that a constructed index, based on markers for the identified genera Escherichia and Blautia, successfully predicted clinical outcomes at Week 8, which exemplifies a way to utilize clinically feasible methods to predict treatment failure. Microbiota changes were restricted to patients who received FMT rather than antibiotic monotherapy, indicating that FMT confers treatment response in a different way than antibiotics. We suggest that early identification of microbial community structures after FMT is of clinical value to predict response to the treatment.}, }
@article {pmid36519027, year = {2022}, author = {Tateishi, AT and Okuma, Y}, title = {Onco-biome in pharmacotherapy for lung cancer: a narrative review.}, journal = {Translational lung cancer research}, volume = {11}, number = {11}, pages = {2332-2345}, pmid = {36519027}, issn = {2218-6751}, abstract = {BACKGROUND AND OBJECTIVE: The gut microbiota (GM) was recently recognized to play an important role in modulating systemic immune responses and is known to influence the effects or adverse events of immune checkpoint blockade (ICB) or carcinogenesis by crosstalk with regulators of cancer-related immunity, and this relationship is complex and multifactorial. Diversity in the gut microbiome and the abundance of specific bacterial species have been identified to be associated with better response and prognosis. Therefore, the purpose of the current interest in the gut microbiome is to enable modulation of the immune system in donor cancer patients by the administration of specific bacterial species and enabling their dominance. To understand this "terra incognita" is to uncover the role of the mechanisms underlying unknown organ functions, and this knowledge will lead to enhanced immunotherapy for lung cancer patients.<br><br>METHODS: In this article, we summarized the literature on the relationship between the microbiome and lung cancer and the potential of the microbiome as a therapeutic target.<br><br>KEY CONTENT AND FINDINGS: This article is organized into the following sections: introduction, methods, microbiota and cancer development, microbiota and lung cancer treatment, future directions, and conclusion.<br><br>CONCLUSIONS: The gut microbiome is currently becoming the hallmark of cancer research and has an established and critical role in regulating antitumor immunity and the response to ICB in patients with lung cancers.}, }
@article {pmid36517893, year = {2022}, author = {Liu, Y and Zhong, X and Lin, S and Xu, H and Liang, X and Wang, Y and Xu, J and Wang, K and Guo, X and Wang, J and Yu, M and Li, C and Xie, C}, title = {Limosilactobacillus reuteri and caffeoylquinic acid synergistically promote adipose browning and ameliorate obesity-associated disorders.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {226}, pmid = {36517893}, issn = {2049-2618}, mesh = {Mice ; Animals ; *Adiposity ; *Limosilactobacillus reuteri ; RNA, Ribosomal, 16S/metabolism ; Propionates ; Obesity/complications ; Diet, High-Fat ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVE: High intake of caffeoylquinic acid (CQA)-rich dietary supplements, such as green coffee bean extracts, offers health-promoting effects on maintaining metabolic homeostasis. Similar to many active herbal ingredients with high pharmacological activities but low bioavailability, CQA has been reported as a promising thermogenic agent with anti-obesity properties, which contrasts with its poor oral absorption. Intestinal tract is the first site of CQA exposure and gut microbes might react quickly to CQA. Thus, it is of interest to explore the role of gut microbiome and microbial metabolites in the beneficial effects of CQA on obesity-related disorders.<br><br>RESULTS: Oral CQA supplementation effectively enhanced energy expenditure by activating browning of adipose and thus ameliorated obesity-related metabolic dysfunctions in high fat diet-induced obese (DIO) mice. Here, 16S rRNA gene amplicon sequencing revealed that CQA treatment remodeled the gut microbiota to promote its anti-obesity actions, as confirmed by antibiotic treatment and fecal microbiota transplantation. CQA enriched the gut commensal species Limosilactobacillus reuteri (L. reuteri) and stimulated the production of short-chain fatty acids, especially propionate. Mono-colonization of L. reuteri or low-dose CQA treatment did not reduce adiposity in DIO mice, while their combination elicited an enhanced thermogenic response, indicating the synergistic effects of CQA and L. reuteri on obesity. Exogenous propionate supplementation mimicked the anti-obesity effects of CQA alone or when combined with L. reuteri, which was ablated by the monocarboxylate transporter (MCT) inhibitor 7ACC1 or MCT1 disruption in inguinal white adipose tissues to block propionate transport.<br><br>CONCLUSIONS: Our data demonstrate a functional axis among L. reuteri, propionate, and beige fat tissue in the anti-obesity action of CQA through the regulation of thermogenesis. These findings provide mechanistic insights into the therapeutic use of herbal ingredients with poor bioavailability via their interaction with the gut microbiota. Video Abstract.}, }
@article {pmid36514447, year = {2022}, author = {Pendrasik, K and Gocel, O and Winter, K and Małecka-Wojciesko, E}, title = {Faecal microbiota transplantation as a non-standard therapy for the treatment of Clostridioides difficile in an ulcerative colitis patient.}, journal = {Przeglad gastroenterologiczny}, volume = {17}, number = {4}, pages = {338-341}, pmid = {36514447}, issn = {1895-5770}, }
@article {pmid36514019, year = {2022}, author = {Podolanczuk, AJ and Kim, JS and Cooper, CB and Lasky, JA and Murray, S and Oldham, JM and Raghu, G and Flaherty, KR and Spino, C and Noth, I and Martinez, FJ and , }, title = {Design and rationale for the prospective treatment efficacy in IPF using genotype for NAC selection (PRECISIONS) clinical trial.}, journal = {BMC pulmonary medicine}, volume = {22}, number = {1}, pages = {475}, pmid = {36514019}, issn = {1471-2466}, support = {U24 HL145265/HL/NHLBI NIH HHS/United States ; UH3 HL145266/HL/NHLBI NIH HHS/United States ; UH3HL145266/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Acetylcysteine/therapeutic use ; Double-Blind Method ; Genotype ; *Idiopathic Pulmonary Fibrosis/drug therapy/genetics ; Treatment Outcome ; Vital Capacity ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Clinical Trials, Phase III as Topic ; }, abstract = {BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with few treatment options. N-acetylcysteine (NAC) is a well-tolerated, inexpensive treatment with antioxidant and anti-fibrotic properties. The National Heart, Lung, and Blood Institute (NHLBI)-sponsored PANTHER (Prednisone Azathioprine and NAC therapy in IPF) trial confirmed the harmful effects of immunosuppression in IPF, and did not show a benefit to treatment with NAC. However, a post hoc analysis revealed a potential beneficial effect of NAC in a subgroup of individuals carrying a specific genetic variant, TOLLIP rs3750920 TT genotype, present in about 25% of patients with IPF. Here, we present the design and rationale for the Phase III, multi-center, randomized, double-blind, placebo-controlled Prospective Treatment Efficacy in IPF Using Genotype for NAC Selection (PRECISIONS) clinical trial.<br><br>METHODS: The PRECISIONS trial will randomize 200 patients with IPF and the TOLLIP rs3750920 TT genotype 1:1 to oral N-acetylcysteine (600&#xa0;mg tablets taken three times a day) or placebo for a 24-month duration. The primary endpoint is the composite of time to 10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplantation, or death from any cause. Secondary endpoints include change in patient-reported outcome scores and proportion of participants with treatment-emergent adverse events. Biospecimens, including blood, buccal, and fecal will be collected longitudinally for future research purposes. Study participants will be offered enrollment in a home spirometry substudy, which explores time to 10% relative FVC decline measured at home, and its comparison with study visit FVC.<br><br>DISCUSSION: The sentinel observation of a potential pharmacogenetic interaction between NAC and TOLLIP polymorphism highlights the urgent, unmet need for better, molecularly focused, and precise therapeutic strategies in IPF. The PRECISIONS clinical trial is the first study to use molecularly-focused techniques to identify patients with IPF most likely to benefit from treatment. PRECISIONS has the potential to shift the paradigm in how trials in this condition are designed and executed, and is the first step toward personalized medicine for patients with IPF. Trial Registration ClinicalTrials.gov identifier: NCT04300920. Registered March 9, 2020. https://clinicaltrials.gov/ct2/show/NCT04300920.}, }
@article {pmid36513509, year = {2022}, author = {Křížová, L and Benešová, I and Špaček, J and Petruželka, L and Vočka, M}, title = {Fecal microbiota transplantation - new possibility to influence the results of therapy of cancer patients.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {35}, number = {6}, pages = {436-440}, doi = {10.48095/ccko2022436}, pmid = {36513509}, issn = {1802-5307}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Carcinoma, Non-Small-Cell Lung ; *Lung Neoplasms ; *Melanoma ; Melanoma, Cutaneous Malignant ; }, abstract = {BACKGROUND: The intestinal microbio-me is essential for the function of the human body, it affects not only metabolism and digestion, but also the immune and neurobehavioral systems. The composition of the human intestinal microbio-me has been of interest to many scientific teams around the world in recent years, aided by the rapid development of molecular genetics methods. Intestinal microbio-me imbalance (so-called dysbio-sis) can help develop several pathological conditions such as autoimmune diseases or can be involved in the process of carcinogenesis. Microbio-me research in oncology has so far focused most on the effect of intestinal microbio-me composition on the effectiveness of checkpoint inhibitors. Differences in the relative proportions of individual bacterial strains and the overall microbio-me diversity in patients treated with checkpoint inhibitors appear to be related to the efficacy of this therapy. Many projects are currently studying the possibility of manipulating the composition of the intestinal microbio-me, especially by means of fecal microbial transplantation (FMT). Two published clinical studies have confirmed that it is possible to overcome resistance to checkpoint inhibitor therapy in malignant melanoma with this method and to re-establish a clinical response after FMT. One of the problems of this effort is the significant diversity in the composition of the microbio-me in different populations. Therefore, knowledge of the microbial composition in a particular population is of key importance. The Department of Oncology of the 1st Faculty of Medicine at Charles University and the General University Hospital in Prague is part of this effort, where a program to investigate intestinal microbio-me composition in patients with non-small cell lung cancer, renal cell carcinoma and malignant melanoma during checkpoint inhibitor therapy has been running for several years.<br><br>PURPOSE: The aim of the publication is to demonstrate the current information and the importance of fecal transplantation in oncology and also to present our currently ongoing research project.}, }
@article {pmid36512976, year = {2023}, author = {Shuwen, H and Yangyanqiu, W and Jian, C and Boyang, H and Gong, C and Jing, Z}, title = {Synergistic effect of sodium butyrate and oxaliplatin on colorectal cancer.}, journal = {Translational oncology}, volume = {27}, number = {}, pages = {101598}, pmid = {36512976}, issn = {1936-5233}, abstract = {BACKGROUND: Oxaliplatin (OXA) is a chemotherapy agent commonly used in the treatment of colorectal cancer (CRC). Sodium butyrate (NaB) has an antitumor effect.<br><br>METHODS: In total, 30 patients in stage III who completed 8 cycles of chemotherapy regimens were recruited for this study. The patients were divided into good and bad groups based on the chemotherapy efficacy. Gas chromatography-mass spectrometry (GC/MS) was used to detect microbial metabolites in stool samples from CRC patients. Cell counting kit-8 (CCK-8), Annexin-V APC/7-AAD double staining, Transwell assays, scratch-wound assays, and EdU assays were used to detect cell proliferation, apoptosis, invasion and migration, respectively. Fluoroelectron microscopy was used to observe the cell structures. To verify the inhibitory effect of NaB and OXA at animal level, a subcutaneous transplanted tumor model was established. Finally, 16S sequencing technology was used to detect intestinal bacteria. GC-MS was used to detect metabolites in mouse stools.<br><br>RESULTS: NaB was a differential metabolite that affected the efficacy of OXA. NAB and oxaliplatin can synergically inhibit cell proliferation, migration and invasion, and induce cell apoptosis. Animal experiments confirmed the inhibitory effect of oxaliplatin and sodium butyrate on tumor in mice. In addition, the intestinal microbe detection and microbial metabolite detection in fecal samples from mice showed significant differences between butyrate-producing bacteria and NaB.<br><br>CONCLUSION: NaB and OXA can synergistically inhibit the proliferation, invasion and metastasis of CRC cells and promote the apoptosis of CRC cells. NaB, as an OXA synergist, has the potential to become a new clinical adjuvant in CRC chemotherapy.}, }
@article {pmid36511953, year = {2022}, author = {Barbut, F and Eckert, C and Lalande, V and Le Neindre, K and Couturier, J}, title = {[Clostridioides difficile: updated recommendations].}, journal = {La Revue du praticien}, volume = {72}, number = {7}, pages = {703-709}, pmid = {36511953}, issn = {2101-017X}, mesh = {Humans ; Aged ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/epidemiology/therapy ; Clostridioides ; *Bacterial Toxins ; Fidaxomicin ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {UPDATED RECOMMENDATIONS Clostridioides difficile is a spore-forming anaerobic enteropathogen responsible for a wide spectrum of clinical features ranging from mild uncomplicated diarrhoea to severe debilitating disease, toxic megacolon, or even perforation and sometimes death. Risk factors for CDI include age >65 years, previous hospitalization and recent antibiotic therapy. Main virulence factors of C. difficile are toxins A (TcdA) and B (TcdB). The emergence and dissemination of a new hypervirulent strain (027/NAP/BI) in 2005 has stimulated clinical and basic research on C. difficile. Major advances have been made regarding the CDI epidemiology (better recognition of community acquired CDI), diagnosis (molecular tests) and therapy (new drugs such as fidaxomicin, bezlotoxumab, and fecal microbiota transplantation) aspects. These advances have allowed the updating of management recommendations, under the aegis of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Antibiotic treatment of CDI depends on both the severity of the infection, and the risk/number of recurrences. Prevention of CDI requires an antimicrobial stewardship policy and the implementation of contact precautions for the infected patients.}, }
@article {pmid36511706, year = {2023}, author = {Fang, H and Feng, X and Xu, T and Zhong, R and Lu, D and Zhang, H and Shen, W and Zhao, Y and Chen, L and Wang, J}, title = {Gut-Spleen Axis: Microbiota via Vascular and Immune Pathways Improve Busulfan-Induced Spleen Disruption.}, journal = {mSphere}, volume = {8}, number = {1}, pages = {e0058122}, pmid = {36511706}, issn = {2379-5042}, mesh = {*Busulfan ; Spleen ; *Microbiota ; Iron ; }, abstract = {Fecal microbiota transplantation (FMT) is an effective means of modulating gut microbiota for the treatment of many diseases, including Clostridioides difficile infections. The gut-spleen axis has been established, and this is involved in the development and function of the spleen. However, it is not understood whether gut microbiota can be used to improve spleen function, especially in spleens disrupted by a disease or an anti-cancer treatment. In the current investigation, we established that alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue anticancer drug busulfan-disrupted spleen vasculature and spleen function. A10-FMT improved the gene and/or protein expression of genes involved in vasculature development, increased the cell proliferation rate, enhanced the endothelial progenitor cell capability, and elevated the expression of the cell junction molecules to increase the vascularization of the spleen. This investigation found for the first time that the reestablishment of spleen vascularization restored spleen function by improving spleen immune cells and iron metabolism. These findings may be used as a strategy to minimize the side effects of anti-cancer drugs or to improve spleen vasculature-related diseases. IMPORTANCE Alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue busulfan disrupted spleen vasculature. A10-FMT improved the cell proliferation rate, endothelial progenitor cell capability, and cell junction molecules to increase vasculature formation in the spleen. This reestablishment restored spleen function by improving spleen immune cells and iron metabolism. These findings are useful for the treatment of spleen vasculature-related diseases.}, }
@article {pmid36509451, year = {2023}, author = {Raue, KD and David, BT and Fessler, RG}, title = {Spinal Cord-Gut-Immune Axis and Its Implications Regarding Therapeutic Development for Spinal Cord Injury.}, journal = {Journal of neurotrauma}, volume = {40}, number = {9-10}, pages = {793-806}, doi = {10.1089/neu.2022.0264}, pmid = {36509451}, issn = {1557-9042}, mesh = {Humans ; *Dysbiosis/etiology ; *Spinal Cord Injuries ; Spinal Cord ; Paralysis ; Central Nervous System ; }, abstract = {Spinal cord injury (SCI) affects ∼1,300,000 people living in the United States. Most research efforts have been focused on reversing paralysis, as this is arguably the most defining feature of SCI. The damage caused by SCI, however, extends past paralysis and includes other debilitating outcomes including immune dysfunction and gut dysbiosis. Recent efforts are now investigating the pathophysiology of and developing therapies for these more distal manifestations of SCI. One exciting avenue is the spinal cord-gut-immune axis, which proposes that gut dysbiosis amplifies lesion inflammation and impairs SCI recovery. This review will highlight the most recent findings regarding gut and immune dysfunction following SCI, and discuss how the central nervous system (CNS), gut, and immune system all coalesce to form a bidirectional axis that can impact SCI recovery. Finally, important considerations regarding how the spinal cord-gut-immune axis fits within the larger framework of therapeutic development (i.e., probiotics, fecal transplants, dietary modifications) will be discussed, emphasizing the lack of interdepartmental investigation and the missed opportunity to maximize therapeutic benefit in SCI.}, }
@article {pmid36507830, year = {2022}, author = {Bonetto, S and Boano, V and Valenzi, E and Saracco, GM and Pellicano, R}, title = {Non-pharmacological strategies to treat irritable bowel syndrome: 2022 update.}, journal = {Minerva gastroenterology}, volume = {68}, number = {4}, pages = {475-481}, doi = {10.23736/S2724-5985.22.03202-8}, pmid = {36507830}, issn = {2724-5365}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/diagnosis ; Analgesics, Opioid/therapeutic use ; Constipation/complications/drug therapy ; Diarrhea/complications/drug therapy ; Abdominal Pain/complications/therapy ; }, abstract = {Irritable bowel syndrome (IBS) is a chronic functional disorder characterized by abdominal pain associated with changes in stool frequency or form, in absence of organic disease. The treatment of IBS is often challenging and should be individually adjusted according to the prevalent symptomatology. Pharmacological treatment for IBS with diarrhea includes peripheral opioid agonists, bile acid sequestrants and antibiotics, while IBS with constipation can be treated with soluble fibers, osmotic agents or prokinetics. In case of abdominal pain, the available pharmacological options are antispasmodics, peripheral opioid agonists or antidepressants. Along with pharmacotherapy, non-pharmacological interventions should be considered as they can play an important role in symptom control. The first-line approach includes lifestyle modifications and dietary advice. Microbiota manipulation through probiotics, prebiotics and symbiotics is a widely used strategy, although the evidence upon the most effective among these in specific IBS subtypes is still unclear. Fecal microbiota transplantation is still in experimental phase for IBS, but it is giving promising results. Psychological therapies may be effective in patients with IBS, despite their application can be limited by long duration, high costs and poor patient's acceptance. Alternative medicine approaches, such as acupuncture, body relaxation techniques, dietary supplements or Chinese herbs, have been proposed; however, the evidence upon their efficacy and safety is still controversial.}, }
@article {pmid36504550, year = {2022}, author = {Li, ZJ and Gou, HZ and Zhang, YL and Song, XJ and Zhang, L}, title = {Role of intestinal flora in primary sclerosing cholangitis and its potential therapeutic value.}, journal = {World journal of gastroenterology}, volume = {28}, number = {44}, pages = {6213-6229}, pmid = {36504550}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Cholangitis, Sclerosing/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; *Autoimmune Diseases ; }, abstract = {Primary sclerosing cholangitis (PSC) is an autoimmune disease characterized by chronic cholestasis, a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis. Gut microbes, consisting of microorganisms colonized in the human gut, play an important role in nutrient intake, metabolic homeostasis, immune regulation, and immune regulation; however, their presence might aid PSC development. Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC. Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria. Dysbiosis of the intestinal flora leads to increased intestinal permeability, homing of intestinal lymphocytes, entry of bacteria and their associated metabolites, such as bile acids, into the liver, stimulation of hepatic immune activation, and promotion of PSC. Currently, PSC effective treatment is lacking. However, a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases (alcoholic liver disease, metabolic fatty liver, cirrhosis, and autoimmune liver disease). In addition, antibiotics, fecal microbiota transplantation, and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis, suggesting their effectiveness for PSC treatment. Therefore, this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.}, }
@article {pmid36504032, year = {2023}, author = {Hallowell, HA and Gao, AL and Suez, J}, title = {Double-edged sword: impact of fecal microbiome transplants on the gut resistome.}, journal = {Current opinion in gastroenterology}, volume = {39}, number = {1}, pages = {16-22}, doi = {10.1097/MOG.0000000000000894}, pmid = {36504032}, issn = {1531-7056}, mesh = {Humans ; *Clostridioides difficile ; Feces ; *Microbiota ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/pharmacology ; }, abstract = {PURPOSE OF REVIEW: Fecal microbiome transplants (FMT) show promise in treating various diseases, such as Clostridioides difficile infections. FMT have also demonstrated the capacity to modulate the collection of antibiotic resistance genes (ARGs), termed the resistome, within the gut. The purpose of this review was to critically evaluate the literature regarding the interaction between FMT and the gut resistome and determine whether FMT could be used specifically to reduce ARG carriage in the gut.<br><br>RECENT FINDINGS: Several studies have demonstrated a decrease in ARG carriage post-FMT administration in various disease states, including recurrent C. difficile infection and after antibiotic usage. However, other studies have reported an expansion of the resistome following FMT. Most studies contained small patient cohorts regardless of the outcome and showed heterogeneity in responses.<br><br>SUMMARY: Research on resistome modulation by FMT is preliminary, and human studies currently lack consensus regarding benefits and risks. From a safety perspective, screening donor samples for ARGs in addition to antibiotic-resistant organisms may be advisable. Additional studies on the mechanisms underlying heterogeneity between studies and individuals are required before FMT is considered an efficient approach for resistome amelioration.}, }
@article {pmid36503158, year = {2023}, author = {Fujikawa, H and Shimizu, H and Nambu, R and Takeuchi, I and Matsui, T and Sakamoto, K and Gocho, Y and Miyamoto, T and Yasumi, T and Yoshioka, T and Arai, K}, title = {Monogenic inflammatory bowel disease with STXBP2 mutations is not resolved by hematopoietic stem cell transplantation but can be alleviated via immunosuppressive drug therapy.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {246}, number = {}, pages = {109203}, doi = {10.1016/j.clim.2022.109203}, pmid = {36503158}, issn = {1521-7035}, mesh = {Humans ; Male ; Diarrhea ; *Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation ; *Inflammatory Bowel Diseases/genetics/therapy ; *Lymphohistiocytosis, Hemophagocytic/genetics/therapy ; Munc18 Proteins/genetics ; Mutation ; }, abstract = {STXBP2, encoding syntaxin-binding protein 2, is involved in intracellular organelle trafficking and is associated with familial hemophagocytic lymphohistiocytosis type 5. Although STXBP2 mutations reportedly cause monogenic inflammatory bowel disease, the clinical course and underlying pathogenic mechanisms remain unclear. We identified a novel mutation in STXBP2 [c.1197delC, p.Ala400fs] in a boy with congenital intractable diarrhea and hemophagocytic lymphohistiocytosis (HLH). HLH was treated with intravenous prednisolone, cyclosporine, and dexamethasone palmitate. Hematopoietic stem cell transplantation (HSCT) along with prophylaxis for graft-versus-host-disease was performed at 5 months of age. Additionally, colonoscopies done before and after HSCT showed mild colitis with cryptitis. The patient showed elevated fecal calprotectin levels and persistent diarrhea even after HSCT and required partial parenteral nutrition. While anti-inflammatory treatment reduced diarrhea, it was not completely normalized even after HSCT, suggesting that the pathogenesis of inflammatory bowel disease associated with STXBP2 mutations involves both hyperinflammation and functional epithelial barrier defects.}, }
@article {pmid36501055, year = {2022}, author = {Huang, L and Liu, Z and Wu, P and Yue, X and Lian, Z and He, P and Liu, Y and Zhou, R and Zhao, J}, title = {Puerariae lobatae Radix Alleviates Pre-Eclampsia by Remodeling Gut Microbiota and Protecting the Gut and Placental Barriers.}, journal = {Nutrients}, volume = {14}, number = {23}, pages = {}, pmid = {36501055}, issn = {2072-6643}, support = {82071669, 82271710, 81870522, and 82173304//National Natural Science Foundation of China/ ; 2022A1515011730 and 2020A1515011339//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Humans ; Animals ; Female ; Mice ; Pregnancy ; *Pre-Eclampsia/metabolism ; Placenta/metabolism ; *Gastrointestinal Microbiome ; Dysbiosis/metabolism ; Proteinuria ; }, abstract = {Pre-eclampsia (PE) is a serious pregnancy complication, and gut dysbiosis is an important cause of it. Puerariae lobatae Radix (PLR) is a medicine and food homologous species; however, its effect on PE is unclear. This study aimed to investigate the efficacy of PLR in alleviating PE and its mechanisms. We used an NG-nitro-L-arginine methyl ester (L-NAME)-induced PE mouse model to examine the efficacy of preventive and therapeutic PLR supplementation. The results showed that both PLR interventions alleviated hypertension and proteinuria, increased fetal and placental weights, and elevated the levels of VEGF and PlGF. Moreover, PLR protected the placenta from oxidative stress via activating the Nrf2/HO-1/NQO1 pathway and mitigated placental damage by increasing intestinal barrier markers (ZO-1, Occludin, and Claudin-1) expression and reducing lipopolysaccharide leakage. Notably, preventive PLR administration corrected gut dysbiosis in PE mice, as evidenced by the increased abundance and positive interactions of beneficial bacteria including Bifidobacterium, Blautia, and Turicibacter. Fecal microbiota transplantation confirmed that the gut microbiota partially mediated the beneficial effects of PLR on PE. Our findings revealed that modulating the gut microbiota is an effective strategy for the treatment of PE and highlighted that PLR might be used as an intestinal nutrient supplement in PE patients.}, }
@article {pmid36499254, year = {2022}, author = {Kim, JE and Roh, YJ and Choi, YJ and Lee, SJ and Jin, YJ and Song, HJ and Seol, AY and Son, HJ and Hong, JT and Hwang, DY}, title = {Dysbiosis of Fecal Microbiota in Tg2576 Mice for Alzheimer's Disease during Pathological Constipation.}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36499254}, issn = {1422-0067}, support = {2020R1l1A1A01052277//National Research Foundation of Korea/ ; F21YY8109033//National Research Foundation of Korea/ ; F22YY8109033//National Research Foundation of Korea/ ; }, mesh = {Animals ; Mice ; *Alzheimer Disease ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Constipation/therapy ; Mice, Transgenic ; }, abstract = {Tg2576 transgenic mice for Alzheimer's disease (AD) exhibited significant phenotypes for neuropathological constipation, but no research has been conducted on the association of the fecal microbiota with dysbiosis. The correlation between fecal microbiota composition and neuropathological constipation in Tg2576 mice was investigated by examining the profile of fecal microbiota and fecal microbiota transplantation (FMT) in 9-10-month-old Tg2576 mice with the AD phenotypes and constipation. Several constipation phenotypes, including stool parameters, colon length, and histopathological structures, were observed prominently in Tg2576 mice compared to the wild-type (WT) mice. The fecal microbiota of Tg2576 mice showed decreases in Bacteroidetes and increases in the Firmicutes and Proteobacteria populations at the phylum level. The FMT study showed that stool parameters, including weight, water content, and morphology, decreased remarkably in the FMT group transplanted with a fecal suspension of Tg2576 mice (TgFMT) compared to the FMT group transplanted with a fecal suspension of WT mice (WFMT). The distribution of myenteric neurons and the interstitial cells of Cajal (ICC), as well as the enteric nervous system (ENS) function, remained lower in the TgFMT group. These results suggest that the neuropathological constipation phenotypes of Tg2576 mice may be tightly linked to the dysbiosis of the fecal microbiota.}, }
@article {pmid36496175, year = {2023}, author = {Mitra, S and Dash, R and Nishan, AA and Habiba, SU and Moon, IS}, title = {Brain modulation by the gut microbiota: From disease to therapy.}, journal = {Journal of advanced research}, volume = {53}, number = {}, pages = {153-173}, pmid = {36496175}, issn = {2090-1224}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; Prebiotics ; Brain/metabolism ; *Brain Diseases/therapy/metabolism ; *Neurodegenerative Diseases/therapy/metabolism ; }, abstract = {BACKGROUND: The gut microbiota (GM) and brain are strongly associated, which significantly affects neuronal development and disorders. GM-derived metabolites modulate neuronal function and influence many cascades in age-related neurodegenerative disorders (NDDs). Because of the dual role of GM in neuroprotection and neurodegeneration, understanding the balance between beneficial and harmful bacteria is crucial for applying this approach to clinical therapies.<br><br>AIM OF THE REVIEW: This review briefly discusses the role of the gut-brain relationship in promoting brain and cognitive function. Although a healthy gut environment is helpful for brain function, gut dysbiosis can disrupt the brain's environment and create a vicious cycle of degenerative cascades. The ways in which the GM population can affect brain function and the development of neurodegeneration are also discussed. In the treatment and management of NDDs, the beneficial effects of methods targeting GM populations and their derivatives, including probiotics, prebiotics, and fecal microbial transplantation (FMT) are also highlighted.<br><br>In this review, we aimed to provide a deeper understanding of the mechanisms of the gut microbe-brain relationship and their twin roles in neurodegeneration progression and therapeutic applications. Here, we attempted to highlight the different pathways connecting the brain and gut, together with the role of GM in neuroprotection and neuronal development. Furthermore, potential roles of GM metabolites in the pathogenesis of brain disorders and in strategies for its treatment are also investigated. By analyzing existing in vitro, in vivo and clinical studies, this review attempts to identify new and promising therapeutic strategies for central nervous system (CNS) disorders. As the connection between the gut microbe-brain relationship and responses to NDD treatments is less studied, this review will provide new insights into the global mechanisms of GM modulation in disease progression, and identify potential future perspectives for developing new therapies to treat NDDs.}, }
@article {pmid36495561, year = {2023}, author = {Hocking, L and Ianiro, G and Leong, RW and Iqbal, T and Kao, D and Cabling, M and Stockwell, S and Romanelli, RJ and Marjanovic, S}, title = {Faecal microbiota transplantation for recurrent C. difficile infections: challenges and improvement opportunities for clinical practice and healthcare systems.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {57}, number = {5}, pages = {549-564}, doi = {10.1111/apt.17309}, pmid = {36495561}, issn = {1365-2036}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Clostridioides difficile ; Feces ; Treatment Outcome ; *Clostridium Infections/therapy ; Delivery of Health Care ; Recurrence ; }, abstract = {BACKGROUND: There is growing interest in faecal microbiota transplantation (FMT) as a treatment for recurrent Clostridioides difficile infection (CDI), but evidence on the diverse requirements for safe, effective and accessible services is fragmented and limited.<br><br>AIMS: To identify key components of FMT provision relating to the patient care pathway, stool donor pathway and wider healthcare system, and to explore variation in practice METHODS: We conducted a narrative review of the literature and consultations with key clinical experts in the field. Evidence is drawn from high-income country contexts, with an emphasis on Australia, Canada, Italy and the United Kingdom as case example countries.<br><br>RESULTS: We identify and discuss key challenges to do with healthcare capacity (workforce, FMT and stool banking facilities), donors and donations, patient access and choice of FMT delivery routes, regulation, costs and reimbursement. We also identify improvement opportunities to increase awareness of FMT and referral processes, physician training, maintaining patient registries and outcome monitoring metrics, in-country regulatory harmonisation and tackling reimbursement challenges and discuss future research needs.<br><br>CONCLUSION: Effectively bringing FMT to patients in a healthcare system requires much more than just the existence of a clinically effective procedure. With FMT being a potentially effective treatment option for recurrent CDI for many patients, a well-rounded understanding of how appropriate FMT capacity can be built and nurtured is important for both healthcare providers and policymakers seeking to improve patient care.}, }
@article {pmid36495304, year = {2023}, author = {Wang, X and Wu, J and Huang, R and Wang, S}, title = {Moxibustion improved the effect of fecal microbiota transplantation donor to dextran sulfate sodium-induced colitis in mice.}, journal = {Anatomical record (Hoboken, N.J. : 2007)}, volume = {306}, number = {12}, pages = {3144-3155}, doi = {10.1002/ar.25135}, pmid = {36495304}, issn = {1932-8494}, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation/methods ; Dextran Sulfate/toxicity ; *Moxibustion ; *Colitis/chemically induced/therapy/microbiology ; Disease Models, Animal ; }, abstract = {Fecal microbiota transplantation (FMT) is beneficial for several gastrointestinal diseases because it alters the intestinal microbiota of recipients. The efficacy of FMT is related to the microbial structure and composition of the donor. Mild moxibustion is a non-invasive and safe traditional Chinese therapy that can regulate the gut microbiota. In this study, we investigated whether moxibustion improved the efficacy of FMT in donors using a dextran sulfate sodium (DSS)-induced colitis mouse model. Normal mice were treated with mild moxibustion at acupoints ST25 and ST36 for 7 days. DSS (2%) was administered for 7 days to induce colitis. FMT was performed on Day 8 and lasted for 7 days. The effect of FMT on mice with DSS was observed on Day 21. Using hematoxylin and eosin staining and immunofluorescence, we analyzed the pathology and cell proliferation after FMT in DSS mice. In addition, using 16 S rDNA sequencing analysis, we investigated the gut microbiota of mice. The results indicated that moxibustion altered the colonic microbial community and increased the relative abundance of specific bacteria without changes in morphology and physiological function in normal mice. FMT using donors with moxibustion reduced body weight loss, inflammation, abnormal microbial community structure, and the relative abundance of some bacteria. These results provide potential strategies for the safe and targeted improvement of FMT donors.}, }
@article {pmid36494024, year = {2023}, author = {Yandle, Z and Gonzalez, G and Carr, M and Matthijnssens, J and De Gascun, C}, title = {A viral metagenomic protocol for nanopore sequencing of group A rotavirus.}, journal = {Journal of virological methods}, volume = {312}, number = {}, pages = {114664}, doi = {10.1016/j.jviromet.2022.114664}, pmid = {36494024}, issn = {1879-0984}, mesh = {Humans ; *Rotavirus/genetics ; *Nanopore Sequencing ; Phylogeny ; *Rotavirus Infections ; Polymerase Chain Reaction ; Genome, Viral ; Genotype ; }, abstract = {AIM: Development of an unbiased methodology using Oxford Nanopore Technology (ONT) sequencing to obtain whole-genome sequences (WGS) of Rotavirus A (RVA) from clinical samples.<br><br>METHODS: 157 RVA qRT-PCR positive faecal samples were enriched by virus-like particle (VLP) purification and host nuclease digestion to enhance the detection of viral nucleic acids and cDNA generated as per the NetoVIR protocol. ONT sequencing was then performed using the ONT Native Barcoding kit (SQK-LSK-109) on the GridION platform. Data was basecalled, demultiplexed and assembled into near complete RVA genomes. The accuracy and quality of the obtained sequences was assessed by comparing to Sanger sequencing and RVA reference genomes.<br><br>RESULTS: The developed protocol generated 146 near-complete RVA WGS out of the 157 RVA-positive clinical samples. The quality of the assembled genomes was assessed by comparison against publicly-available sequences with results showing 98.76 %&#xa0;&#xb1;&#xa0;0.03 % similarity and >&#xa0;90 % genome coverage. A concordance assessment was performed comparing the identity of partial RVA VP7 and VP4 segments obtained by Sanger sequencing (n&#xa0;=&#xa0;51) against corresponding nanopore sequences which demonstrated an overall identity of 100.0 %&#xa0;&#xb1;&#xa0;0.02 %.<br><br>CONCLUSIONS: The nanopore protocol generated both high quality and accurate RVA WGS extracted from faecal samples. This protocol can be extended to other viral agents in other sample types.}, }
@article {pmid36484924, year = {2024}, author = {Kawabata, S and Takagaki, M and Nakamura, H and Nishida, T and Terada, E and Kadono, Y and Izutsu, N and Takenaka, T and Matsui, Y and Yamada, S and Fukuda, T and Nakagawa, R and Kishima, H}, title = {Association of Gut Microbiome with Early Brain Injury After Subarachnoid Hemorrhage: an Experimental Study.}, journal = {Translational stroke research}, volume = {15}, number = {1}, pages = {87-100}, pmid = {36484924}, issn = {1868-601X}, mesh = {Rats ; Male ; Animals ; Blood-Brain Barrier ; Rats, Sprague-Dawley ; *Subarachnoid Hemorrhage/complications ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Brain ; *Brain Injuries/complications ; *Brain Edema/complications ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Water/pharmacology ; }, abstract = {The occurrence of early brain injury (EBI) following subarachnoid hemorrhage (SAH) is crucial in the prognosis of SAH; however, no effective treatment for EBI has been developed. Gut microbiome (GM) composition influences the outcome of various diseases, including ischemic stroke. Here, we evaluated whether prior GM alteration could prevent EBI following SAH. We altered the GM of 7-week-old male rats by administering antibiotic-containing water for 2 weeks and performing fecal microbiome transplantation after antibiotic induction. Composition of the GM was profiled using 16S rRNA. We induced SAH by injecting blood in the subarachnoid space of control rats and rats with altered GM. We evaluated EBI indicators such as neurological score, brain water content, Evans blue extravasation, and neuronal injury. Additionally, we studied inflammatory cells using immunohistochemistry, immunocytochemistry, quantitative PCR, and flow cytometry. EBI was significantly averted by alterations in GM using antibiotics. The altered GM significantly prevented neutrophil infiltration into the brain among inflammatory cells, and this anti-inflammatory effect was observed immediately following SAH onset. The altered GM also prevented neutrophil extracellular trap formation in the brain and blood, indicating the systemic protective effect. The cause of the protective effect was attributed to a significant decrease in aged neutrophils (CXCR4[high] CD62L[low]) by the altered GM. These protective effects against EBI disappeared when the altered GM was recolonized with normal flora. Our findings demonstrated that EBI following SAH is associated with GM, which regulated neutrophil infiltration.}, }
@article {pmid36484871, year = {2023}, author = {Gu, X and Chen, ZH and Zhang, SC}, title = {Fecal microbiota transplantation in childhood: past, present, and future.}, journal = {World journal of pediatrics : WJP}, volume = {19}, number = {9}, pages = {813-822}, pmid = {36484871}, issn = {1867-0687}, support = {30700917//National Natural Science Foundation of China/ ; 81570465//National Natural Science Foundation of China/ ; }, mesh = {Child ; Humans ; Fecal Microbiota Transplantation/methods ; Feces ; *Clostridioides difficile ; *Autism Spectrum Disorder ; *Inflammatory Bowel Diseases ; Recurrence ; *Non-alcoholic Fatty Liver Disease ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been well described in the treatment of pediatric diseases; however, the latest updates regarding its use in children are unclear and the concepts involved need to be revisited.<br><br>DATA SOURCES: We performed advanced searches in the MEDLINE, EMBASE, and Cochrane databases using the keywords "Fecal microbiota transplantation OR Fecal microbiota transfer" in the [Title/Abstract] to identify relevant articles published in English within the last five years. To identify additional studies, reference lists of review articles and included studies were manually searched. Retrieved manuscripts (case reports, reviews, and abstracts) were assessed by the authors.<br><br>RESULTS: Among the articles, studies were based on the mechanism (n&#x2009;=&#x2009;28), sample preparation (n&#x2009;=&#x2009;9), delivery approaches (n&#x2009;=&#x2009;23), safety (n&#x2009;=&#x2009;26), and indications (n&#x2009;=&#x2009;67), including Clostridium difficile infection (CDI) and recurrent C. difficile infection (rCDI; n&#x2009;=&#x2009;21), non-alcoholic fatty liver disease (NAFLD; n&#x2009;=&#x2009;10), irritable bowel syndrome (IBS; n&#x2009;=&#x2009;5), inflammatory bowel disease (IBD; n&#x2009;=&#x2009;15), diabetes (n&#x2009;=&#x2009;5), functional constipation (FC; n&#x2009;=&#x2009;4), and autism spectrum disorder (ASD; n&#x2009;=&#x2009;7).<br><br>CONCLUSIONS: Concepts of FMT in pediatric diseases have been updated with respect to underlying mechanisms, methodology, indications, and safety. Evidence-based clinical trials for the use of FMT in pediatric diseases should be introduced to resolve the challenges of dosage, duration, initiation, and the end point of treatment.}, }
@article {pmid36483198, year = {2022}, author = {Zhou, J and Zhang, R and Guo, P and Li, P and Huang, X and Wei, Y and Yang, C and Zhou, J and Yang, T and Liu, Y and Shi, S}, title = {Effects of intestinal microbiota on pharmacokinetics of cyclosporine a in rats.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1032290}, pmid = {36483198}, issn = {1664-302X}, abstract = {BACKGROUND: Intestinal microbiota has been confirmed to influencing the pharmacokinetic processes of a variety of oral drugs. However, the pharmacokinetic effects of the gut microbiota on cyclosporine A, a drug with a narrow therapeutic window, remain to be studied.<br><br>METHOD: Twenty-one rats were randomly divided into three groups: (a) control group (CON), (b) antibiotic treatment group (ABT) and (c) fecal microbe transplantation group (FMT). The ABT group was administrated with water containing multiple antibiotics to deplete microorganisms. FMT was with the same treatment, followed by oral administration of conventional rat fecal microorganisms for normalization.<br><br>RESULT: The bioavailability of CSA increased by 155.6% after intestinal microbes were consumed by antibiotics. After intestinal microbiota reconstruction by fecal transplantation, the increased bioavailability was significantly reduced and basically returned to the control group level. Changes in gut microbiota alter the protein expression of CYP3A1, UGT1A1 and P-gp in liver. The expressions of these three proteins in ABT group were significantly lower than those in CON and FMT groups. The relative abundance of Alloprevolleta and Oscillospiraceae UCG 005 was negatively correlated with CSA bioavailability while the relative abundance of Parasutterella and Eubacterium xylanophilum group was negatively correlated with CSA bioavailability.<br><br>CONCLUSION: Intestinal microbiota affects the pharmacokinetics of CSA by regulating the expression of CYP3A1, UGT1A1 and P-GP.}, }
@article {pmid36479654, year = {2023}, author = {Garoufalia, Z and Gefen, R and Emile, SH and Silva-Alvarenga, E and Freund, MR and Horesh, N and Wexner, SD}, title = {Outcomes of graciloplasty in the treatment of fecal incontinence: a systematic review and meta-analysis of the literature.}, journal = {Techniques in coloproctology}, volume = {27}, number = {6}, pages = {429-441}, pmid = {36479654}, issn = {1128-045X}, mesh = {Female ; Animals ; Humans ; *Fecal Incontinence/etiology/surgery/diagnosis ; Treatment Outcome ; Anal Canal/surgery ; *Plastic Surgery Procedures/adverse effects ; Reoperation ; }, abstract = {BACKGROUND: Patients with refractory fecal incontinence symptoms can be treated with several surgical procedures including graciloplasty. Reported outcomes and morbidity rates of this procedure are highly variable. The aim of this study was to assess continence rate and safety of dynamic and adynamic graciloplasty.<br><br>METHODS: PubMed and Google Scholar databases were systematically searched from inception until January 2022 according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Reviews, animal studies, studies with patients&#x2009;<&#x2009;18&#xa0;years or&#x2009;<&#x2009;10 patients, with no success rate reported or non-English text, were excluded. Main outcome measures were overall continence and morbidity rates of each technique.<br><br>RESULTS: Fourteen studies were identified, incorporating a total of 450 patients (337 females), published between 1980 and 2021. Most common etiology of incontinence (35.5%-n&#x2009;=&#x2009;160) was obstetric trauma followed by anorectal trauma (20%-n&#x2009;=&#x2009;90). The weighted mean rate of continence after dynamic graciloplasty was 69.1% (95% CI 0.53-0.84%, I[2]&#x2009;=&#x2009;90%) compared to 71% (95% CI 0.54-0.87, I[2]&#x2009;=&#x2009;82.5%) after adynamic. Although the weighted mean short-term complication rate was lower in the dynamic group (26% versus 40%), when focusing on complications requiring intervention under general anesthesia, there was a much higher incidence (43.4% versus 10.5%) in the dynamic group. The weighted mean rate of long-term complications was 59.4% (95% CI 0.13-1.04%, I[2]&#x2009;=&#x2009;97.7%) in the dynamic group, almost twice higher than in the adynamic group [30% (95% CI -&#x2009;0.03 to 0.63), I[2]&#x2009;=&#x2009;95.8%]. Median follow-up ranged from 1 to 13&#xa0;years.<br><br>CONCLUSIONS: Our data suggest that graciloplasty may be considered for incontinent patients. Dynamic graciloplasty may harbor higher risk for reoperation and complications compared to adynamic.&#xa0;The fact that the functional results between adynamic and dynamic graciloplasty are equivalent and the morbidity rate of adynamic graciloplasty is significantly lower reinforce the graciloplasty as an option to treat appropriately selected patients with fecal incontinence.}, }
@article {pmid36479155, year = {2022}, author = {Philips, CA and Ahamed, R and Rajesh, S and Singh, S and Tharakan, A and Abduljaleel, JK and Augustine, P}, title = {Clinical outcomes and gut microbiota analysis of severe alcohol-associated hepatitis patients undergoing healthy donor fecal transplant or pentoxifylline therapy: single-center experience from Kerala.}, journal = {Gastroenterology report}, volume = {10}, number = {}, pages = {goac074}, pmid = {36479155}, issn = {2052-0034}, abstract = {BACKGROUND: Severe alcohol-associated hepatitis (SAH) patients with infections have a high short-term mortality rate. Gut microbiota dysbiosis plays an important role in the pathogenesis of SAH. Preliminary studies have demonstrated long-term benefits with healthy donor fecal microbiota transplantation (FMT). Data on FMT compared with pentoxifylline for SAH and relevant gut microbial changes are lacking in literature.<br><br>METHODS: From January 2019 to February 2021, retrospective analysis of a single hospital's records revealed 47 SAH patients undergoing FMT (100&#x2009;mL/day via nasoduodenal tube for 7&#x2009;days) and 25 matched patients receiving pentoxifylline (400&#x2009;mg/8 h for 28&#x2009;days). The primary end point was a 6-month survival rate. Secondary end points included incidence of ascites, hepatic encephalopathy, infections, acute kidney injury, and gut microbiota changes between post-therapy groups. Biomarker discovery and network analysis were also performed to identify significant taxa of gut microbiota in post-treatment groups in retrospectively stored stool samples.<br><br>RESULTS: All were males. The 6-month survival rate was higher in the patients undergoing FMT than in patients receiving pentoxifylline (83.0% vs 56.0%, P&#x2009;=&#x2009;0.012). At the end of 6-month follow-up, the incidences of clinically significant ascites (56.0% vs 25.5%, P&#x2009;=&#x2009;0.011), hepatic encephalopathy (40.0% vs 10.6%, P&#x2009;=&#x2009;0.003), and critical infections (52.0% vs 14.9%, P&#x2009;<&#x2009;0.001) in patients administered pentoxifylline were significantly higher than those in patients treated with FMT. At 3&#x2009;months, biomarker analysis revealed a significant abundance of Bifidobacterium and Eggerthella in the FMT group and the pentoxifylline group, respectively. At 6&#x2009;months, Bifidobacterium in the FMT group and pathogenic Aerococcaceae in the pentoxifylline group were notable. Network analysis showed beneficial taxa (Bifidobacterium) as a central influencer in those undergoing FMT at 6&#x2009;months.<br><br>CONCLUSIONS: Healthy donor FMT improved survival rate and reduced liver-related complications compared with pentoxifylline. These clinical benefits were associated with favorable modulation of intestinal bacterial communities. Difficult-to-treat SAH patients may be safely bridged to transplantation using FMT. Controlled trials evaluating long-term outcomes are an unmet need.}, }
@article {pmid36478314, year = {2023}, author = {Akita, Y and Higashiyama, M and Kurihara, C and Ito, S and Nishii, S and Mizoguchi, A and Inaba, K and Tanemoto, R and Sugihara, N and Hanawa, Y and Wada, A and Horiuchi, K and Okada, Y and Narimatsu, K and Komoto, S and Tomita, K and Takei, F and Satoh, Y and Saruta, M and Hokari, R}, title = {Ameliorating Role of Hydrogen-Rich Water Against NSAID-Induced Enteropathy via Reduction of ROS and Production of Short-Chain Fatty Acids.}, journal = {Digestive diseases and sciences}, volume = {68}, number = {5}, pages = {1824-1834}, pmid = {36478314}, issn = {1573-2568}, mesh = {Mice ; Animals ; Reactive Oxygen Species ; *Intestinal Diseases/chemically induced ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Anti-Inflammatory Agents/adverse effects ; Fatty Acids, Volatile ; Hydrogen/pharmacology/therapeutic use ; Water ; }, abstract = {BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy, the mechanism of which is involved in oxidative stress, can be lethal due to hemorrhage. Thus, we aimed to investigate the effect of hydrogen-rich water (HRW), in terms of oxidative stress, on intestinal mucosal damage as well as changes in the gut microbiome and the short-chain fatty acids (SCFAs) content in feces.<br><br>METHODS: Hydrogen-rich water was orally administered for 5 days to investigate the effectiveness of indomethacin-induced enteropathy in mice. Small intestinal damage and luminal reactive oxygen species (ROS) were evaluated to investigate the ameliorating effects of hydrogen. Then, components of the gut microbiome were analyzed; fecal microbiota transplantation (FMT) was performed using the cecal contents obtained from mice drinking HRW. The cecal contents were analyzed for the SCFAs content. Finally, cells from the macrophage cell line RAW264 were co-cultured with the supernatants of cecal contents.<br><br>RESULTS: Hydrogen-rich water significantly ameliorated IND-induced enteropathy histologically and reduced the expression of IND-induced inflammatory cytokines. Microscopic evaluation revealed that luminal ROS was significantly reduced and that HRW did not change the gut microbiota; however, FMT from HRW-treated animals ameliorated IND-induced enteropathy. The SCFA content in the cecal contents of HRW-treated animals was significantly higher than that in control animals. The supernatant had significantly increased interleukin-10 expression in RAW264 cells in vitro.<br><br>CONCLUSION: Hydrogen-rich water ameliorated NSAID-induced enteropathy, not only via direct antioxidant effects but also via anti-inflammatory effects by increasing luminal SCFAs. These results suggest that hydrogen may have therapeutic potential in small intestinal inflammatory diseases.}, }
@article {pmid36476497, year = {2022}, author = {Corriero, A and Gadaleta, RM and Puntillo, F and Inchingolo, F and Moschetta, A and Brienza, N}, title = {The central role of the gut in intensive care.}, journal = {Critical care (London, England)}, volume = {26}, number = {1}, pages = {379}, pmid = {36476497}, issn = {1466-609X}, mesh = {Humans ; *Critical Care ; }, abstract = {Critically ill patients undergo early impairment of their gut microbiota (GM) due to routine antibiotic therapies and other environmental factors leading to intestinal dysbiosis. The GM establishes connections with the rest of the human body along several axes representing critical inter-organ crosstalks that, once disrupted, play a major role in the pathophysiology of numerous diseases and their complications. Key players in this communication are GM metabolites such as short-chain fatty acids and bile acids, neurotransmitters, hormones, interleukins, and toxins. Intensivists juggle at the crossroad of multiple connections between the intestine and the rest of the body. Harnessing the GM in ICU could improve the management of several challenges, such as infections, traumatic brain injury, heart failure, kidney injury, and liver dysfunction. The study of molecular pathways affected by the GM in different clinical conditions is still at an early stage, and evidence in critically ill patients is lacking. This review aims to describe dysbiosis in critical illness and provide intensivists with a perspective on the potential as adjuvant strategies (e.g., nutrition, probiotics, prebiotics and synbiotics supplementation, adsorbent charcoal, beta-lactamase, and fecal microbiota transplantation) to modulate the GM in ICU patients and attempt to restore eubiosis.}, }
@article {pmid36475195, year = {2022}, author = {Kanlioz, M and Ekici, U and Ferhatoğlu, MF}, title = {Total Gastrointestinal Flora Transplantation in the Treatment of Leaky Gut Syndrome and Flora Loss.}, journal = {Cureus}, volume = {14}, number = {11}, pages = {e31071}, pmid = {36475195}, issn = {2168-8184}, abstract = {Introduction The aim of this work was to treat patients with leaky gut syndrome (LGS) and gastrointestinal flora loss in a simple, inexpensive, permanent and effective way without the need for further treatment. Methods A total gastrointestinal flora transplantation (TGFT) procedure is performed by simultaneously transferring the "flora" taken from approximately 30 different anatomical sites, from the mouth to the anus, of healthy donors to the corresponding anatomical site of the patient using the endoscopic lavage method. Results Of the patients, 25 (44.6%) were female and 31 (55.4%) were male, totaling 56 (100%). The mean age was 32.88±15.78 years. Among the 56 patients enrolled in the study, TGFT had no efficacy in one patient, five patients underwent repeat TGFT during a mean follow-up period of 23.73±16.74 months, and the treatment was permanent in 50 patients; our success rate during the follow-up period was 89.3%. Conclusion In LGS, TGFT should be the gold standard treatment.}, }
@article {pmid36474346, year = {2022}, author = {Wang, D and Pham, VT and Steinert, RE and Zhernakova, A and Fu, J}, title = {Microbial vitamin production mediates dietary effects on diabetic risk.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2154550}, pmid = {36474346}, issn = {1949-0984}, mesh = {Humans ; Vitamins ; Health Promotion ; *Gastrointestinal Microbiome ; *Diabetes Mellitus ; Thiamine ; }, abstract = {Adequate levels of essential vitamins are important for the prevention of diabetes. While the main efforts to address this are currently focused on the intake of vitamin supplements, improving and maintaining intrinsic vitamin production capacity, which is determined by gut microbes, has received insufficient attention. In this study, we systematically investigated the relationship between gut microbial vitamin production and factors related to diabetes and cardiometabolic health in a deeply phenotyped cohort, Lifelines-DEEP (N = 1,135). We found that blood glucose-related factors, lipids, circulating inflammation, and fecal short-chain fatty acids are associated with gut microbial vitamin production. Use of laxatives and metformin are associated with increased levels of vitamin B1/B6 biosynthesis pathways. We further reveal a mediatory role for microbial vitamin B1/B2 production on the influence of fruit intake on diabetes risk. This study provides preliminary evidence for microbiome-targeted vitamin metabolism interventions to promote health.}, }
@article {pmid36473618, year = {2023}, author = {Liu, CS and Hu, YX and Luo, ZY and Qiu, CW and Deng, XH and Chen, FL}, title = {Xianglian pill modulates gut microbial production of succinate and induces regulatory T cells to alleviate ulcerative colitis in rats.}, journal = {Journal of ethnopharmacology}, volume = {303}, number = {}, pages = {116007}, doi = {10.1016/j.jep.2022.116007}, pmid = {36473618}, issn = {1872-7573}, mesh = {Rats ; Animals ; *Colitis, Ulcerative/chemically induced/drug therapy/pathology ; T-Lymphocytes, Regulatory ; Succinic Acid/metabolism/pharmacology/therapeutic use ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics/metabolism ; Colon ; Succinates/pharmacology ; Dextran Sulfate/toxicity ; *Colitis/drug therapy ; Disease Models, Animal ; }, abstract = {Xianglian pill (XLP), a traditional Chinese formula, is widely used as treatment for ulcerative colitis (UC) in China. However, the mechanism of its therapeutic effect is still unclear.<br><br>AIM OF THE STUDY: Our previous studies showed a low oral bioavailability and a predominant distribution of major XLP ingredients in the gut. In the present study, we aimed to explore the mechanism of action of XLP on UC with respect to the regulation of gut microecology.<br><br>MATERIALS AND METHODS: UC model rats established using 5% dextran sulfate sodium were treated with XLP. After the treatment period, bodyweight, colon length, histopathology, and inflammatory changes were evaluated. Further, changes in gut microbiota structure were detected via 16S rRNA sequencing, and microbial metabolites in feces were analyzed via a metabolomic assay. Antibiotic intervention and fecal microbiota transplantation were also employed to explore the involvement of gut microbiota, while the level of regulatory T cells (Tregs) in mesenteric lymph nodes was determined via flow cytometry. Transcriptome sequencing was also performed to determine colonic gene changes.<br><br>RESULTS: XLP alleviated colonic injury, inflammation, and gut microbial dysbiosis in UC model rats and also changed microbial metabolite levels. Particularly, it significantly decreased succinate level in the tyrosine pathway. We also observed that fecal microbiota derived from XLP-treated rats conferred resilience to UC model rats. However, this therapeutic effect of XLP on UC was inhibited by succinate. Moreover, XLP increased the level of anti-inflammatory cellular Tregs via gut microbiota. However, this beneficial effect was counteracted by succinate supplementation. Further, XLP induced the differentiation of Treg possibly by the regulation of the PHD2/HIF-1&#x3b1; pathway via decreasing microbial succinate production.<br><br>CONCLUSIONS: Our findings indicated that XLP exerts its therapeutic effects on UC mainly via the gut microbiota-succinate-Treg differentiation axis.}, }
@article {pmid36473615, year = {2023}, author = {Zádori, ZS and Király, K and Al-Khrasani, M and Gyires, K}, title = {Interactions between NSAIDs, opioids and the gut microbiota - Future perspectives in the management of inflammation and pain.}, journal = {Pharmacology &amp; therapeutics}, volume = {241}, number = {}, pages = {108327}, doi = {10.1016/j.pharmthera.2022.108327}, pmid = {36473615}, issn = {1879-016X}, mesh = {Animals ; Humans ; Analgesics, Opioid/adverse effects ; *Gastrointestinal Microbiome ; Dysbiosis/drug therapy/microbiology ; *Diabetes Mellitus, Type 2/drug therapy ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Inflammation/drug therapy ; *Arthritis, Rheumatoid/drug therapy ; *Neuralgia/drug therapy ; }, abstract = {The composition of intestinal microbiota is influenced by a number of factors, including medications, which may have a substantial impact on host physiology. Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics are among those widely used medications that have been shown to alter microbiota composition in both animals and humans. Although much effort has been devoted to identify microbiota signatures associated with these medications, much less is known about the underlying mechanisms. Mucosal inflammation, changes in intestinal motility, luminal pH and bile acid metabolism, or direct drug-induced inhibitory effect on bacterial growth are all potential contributors to NSAID- and opioid-induced dysbiosis, however, only a few studies have addressed directly these issues. In addition, there is a notable overlap between the microbiota signatures of these drugs and certain diseases in which they are used, such as spondyloarthritis (SpA), rheumatoid arthritis (RA) and neuropathic pain associated with type 2 diabetes (T2D). The aims of the present review are threefold. First, we aim to provide a comprehensive up-to-date summary on the bacterial alterations caused by NSAIDs and opioids. Second, we critically review the available data on the possible underlying mechanisms of dysbiosis. Third, we review the current knowledge on gut dysbiosis associated with SpA, RA and neuropathic pain in T2D, and highlight the similarities between them and those caused by NSAIDs and opioids. We posit that drug-induced dysbiosis may contribute to the persistence of these diseases, and may potentially limit the therapeutic effect of these medications by long-term use. In this context, we will review the available literature data on the effect of probiotic supplementation and fecal microbiota transplantation on the therapeutic efficacy of NSAIDs and opioids in these diseases.}, }
@article {pmid36472469, year = {2022}, author = {Gan, B and Sun, N and Lai, J and Wan, Z and Li, L and Wang, Y and Zeng, Y and Zeng, D and Pan, K and Fang, J and Shu, G and Wang, H and Xin, J and Ni, X}, title = {Dynamic Monitoring of Changes in Fecal Flora of Giant Pandas in Mice: Co-Occurrence Network Reconstruction.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0199122}, pmid = {36472469}, issn = {2165-0497}, abstract = {Giant pandas are uniquely vulnerable mammals in western China. It is important to develop an animal model to explore the intestinal flora of giant pandas to understand the relationship between digestive diseases and flora. Existing animal models of intestinal flora focus on human flora-associated animals, such as mice, and there is a very limited amount of knowledge regarding giant panda flora-associated animals. To fill this gap, fecal microorganisms from giant pandas were transplanted into pseudosterile and germfree mice using single and multiple gavages. Fecal samples were collected from mice at four time points after transplantation for microbial community analysis. We determined that compared to pseudosterile mice, the characteristics of intestinal flora in pandas were better reproduced in germfree mice. There was no significant difference in microbial diversity between germfree mice and giant panda gut microbes from day 3 to day 21. Germfree mice at the phylum level possessed large amounts of Firmicutes and Proteobacteria, and at the genus level, Escherichia-Shigella, Clostridium sensu stricto 1, and Streptococcus dominated the intestinal flora structure. The microbial community co-occurrence network based on indicator species indicated that germfree mice transplanted with fecal bacteria tended to form a microbial community co-occurrence network similar to that of giant pandas, while pseudosterile mice tended to restore the microbial community co-occurrence network originally present in these mice. Our data are helpful for the study of giant panda flora-associated animals and provide new insights for the in vitro study of giant panda intestinal flora. IMPORTANCE The giant panda is a unique vulnerable mammal in western China, and its main cause of death is digestive system diseases regardless of whether these animals are in the wild or in captivity. The relationship between the intestinal flora and the host exerts a significant impact on the nutrition and health of the giant pandas. However, the protected status of the giant panda has made in vivo, repeatable, and large-sample sampling studies of their intestinal flora difficult. This greatly hinders the research depth of the giant panda intestinal flora from the source. The development and utilization of specific animal models to simulate the structure and characteristics of the intestinal flora provide another means to deal with these research limitations. However, current research examining giant panda flora-associated animals is limited. This study is the first to reveal dynamic changes in the fecal flora of giant pandas in mice after transplantation.}, }
@article {pmid36472435, year = {2023}, author = {Zhang, B and Yang, L and Ning, H and Cao, M and Chen, Z and Chen, Q and Lian, G and Tang, H and Wang, Q and Wang, J and Lin, Z and Wen, J and Liu, Y and Xuan, J and Li, X and Lin, A and He, J and Zhang, L and Hou, X and Zeng, Q and Xiao, C}, title = {A Matching Strategy To Guide Donor Selection for Ulcerative Colitis in Fecal Microbiota Transplantation: Meta-Analysis and Analytic Hierarchy Process.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0215921}, pmid = {36472435}, issn = {2165-0497}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy/microbiology ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Analytic Hierarchy Process ; Donor Selection ; Treatment Outcome ; Feces/microbiology ; Bacteria/genetics ; }, abstract = {Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of ulcerative colitis (UC). However, preliminary trials showed that only a subset of patients responded to FMT, and the heterogeneity in donor gut microbiota probably played important roles in patients' responses, implying the significance of matching an appropriate donor to a specified patient. We developed a strategy to build a donor-recipient matching model to guide rational donor selection for UC in FMT. We collected and uniformly reanalyzed 656 fecal 16S rRNA gene sequencing samples (350 from UC patients and 306 from healthy subjects) from 9 studies. Significantly lower α-diversity indexes were observed in UC patients by random effects model. Thirty-four bacterial genera and 34 predicted pathways were identified with significant odds ratios and classification potentials for UC patients. Based on six bacterial indicators, including richness, overall distance, genera, and pathways (beneficial and harmful), the analytic hierarchy process-based donor-recipient matching model was set to rank and select appropriate donors for patients with UC. Finally, the model showed favorable classification powers (>70%) for FMT effectiveness in two previous clinical trials. This study revealed the dysbiosis of fecal bacterial diversity, composition, and predicted pathways of patients with UC by meta-analysis and hereby developed a donor-recipient matching strategy to guide donor selection for UC in FMT. This strategy can also be applied to other diseases associated with gut microbiota. IMPORTANCE Modulation of gut microbiota by FMT from donors has been applied to the treatment of UC and yielded variable effectiveness in clinical trials. One possibility is that this variable effectiveness was related to donor selection, as a patient's response to FMT may rely on the capability of the used donor's microbiota to restore the specific gut disturbances of the patient. However, the biggest issues on the practical level are what should be considered in the selection process and how to set up such a donor-recipient matching model. In this study, we presented a bacterial profile-based donor-recipient matching strategy to guide donor selection for UC in FMT by first meta-analysis of 656 fecal 16S rRNA gene sequencing samples from 9 studies to identify significant indicators and then setting up the model by an analytic hierarchy process. The applicability and accuracy of this model were verified in the data sets from two previous FMT clinical studies. Our data indicate that the donor-recipient matching model built in this study enables researchers to rationally select donors for UC patients in FMT clinical practice, although it needs more samples and prospective trials for validation. The strategy adopted in this study to leverage existing data sets to build donor-recipient matching models for precision FMT is feasible for other diseases associated with gut microbiota.}, }
@article {pmid36469298, year = {2023}, author = {Pande, A and Sharma, S and Khillan, V and Rastogi, A and Arora, V and Shasthry, SM and Vijayaraghavan, R and Jagdish, R and Kumar, M and Kumar, G and Mondot, S and Dore, J and Sarin, SK}, title = {Fecal microbiota transplantation compared with prednisolone in severe alcoholic hepatitis patients: a randomized trial.}, journal = {Hepatology international}, volume = {17}, number = {1}, pages = {249-261}, pmid = {36469298}, issn = {1936-0541}, mesh = {Humans ; Prednisolone/therapeutic use ; Fecal Microbiota Transplantation/methods ; *Hepatitis, Alcoholic/drug therapy ; *Microbiota ; Treatment Outcome ; }, abstract = {BACKGROUND: Severe alcoholic hepatitis (SAH) has high 90-day mortality. Prednisolone therapy has shown modest survival benefits over placebo at 28 but not 90 days. Fecal microbial transplantation (FMT) has shown promise in these patients. We compared the efficacy and safety of the two therapies in SAH patients.<br><br>METHODS: Steroid eligible SAH patients were randomized in an open-label study to prednisolone (n&#x2009;=&#x2009;60) 40&#xa0;mg/day for 28&#xa0;days (assessed at day-7 for continuation) or healthy donor FMT (n&#x2009;=&#x2009;60) through naso-duodenal tube, daily for seven days. Primary outcome of study was day-90 survival.<br><br>RESULTS: Patients in prednisolone and FMT arms were comparable at baseline (discriminant function score 65&#x2009;&#xb1;&#x2009;16.2 and 68&#x2009;&#xb1;&#x2009;14, MELD score 17.1 and 16.5, respectively). Of 120 patients, 112 [prednisolone-57; FMT-55] completed trial. As per intention-to-treat analysis, 90-day survival was achieved by 56.6% (34/60) patients in prednisolone and 75% (45/60) in FMT group (p&#x2009;=&#x2009;0.044, FMT HR&#x2009;=&#x2009;0.528, 95%CI 0.279-0.998). Secondary outcome of 28-day survival [78.33% (47/60) and 88.33% (53/60) (p&#x2009;=&#x2009;0.243, FMT HR&#x2009;=&#x2009;0.535, 95%CI 0.213-1.34)] with comparable severity scores over time between both arms. Infections accounted for 11 (19.3%) and 2 (3.6%) deaths in prednisolone and FMT groups, respectively (p&#x2009;=&#x2009;0.01). Path-tracing showed a slow establishment of microbiota and alpha diversity (Shannon index) improvement by day-28 (p&#x2009;=&#x2009;0.029). FMT resulted in 23 new taxa by day-28, reduction from baseline in pathogenic taxa [Campylobacter (19-fold, p&#x2009;=&#x2009;0.035), anaerobes (Parcubacteria, Weisella and Leuconostocaceae)], and increase of Alphaproteobacteria [~&#x2009;sevenfold, p&#x2009;=&#x2009;0.047] and Thaumarcheota (known ammonia oxidizer, p&#x2009;=&#x2009;0.06). Lachnospiraceae (p&#x2009;=&#x2009;0.008), Prevotella and Viellonella communities in gut favored survival (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: In severe alcoholic hepatitis, FMT is safe and improves 90-day survival and reduces infections by favorably modulating microbial communities. It can be a useful alternative to prednisolone therapy.}, }
@article {pmid36469257, year = {2023}, author = {Sankararaman, S and Noriega, K and Velayuthan, S and Sferra, T and Martindale, R}, title = {Gut Microbiome and Its Impact on Obesity and Obesity-Related Disorders.}, journal = {Current gastroenterology reports}, volume = {25}, number = {2}, pages = {31-44}, doi = {10.1007/s11894-022-00859-0}, pmid = {36469257}, issn = {1534-312X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/complications ; Dysbiosis/complications ; *Probiotics/therapeutic use ; Prebiotics ; Obesity/complications ; Inflammation/complications ; Fecal Microbiota Transplantation ; }, abstract = {PURPOSE OF REVIEW: The prevalence of overweight and obesity has been increasing worldwide at an alarming rate. Gut microbiota intimately influence host energy metabolism, and immune response. Studies indicate a prominent role of gut dysbiosis in propagating inflammation that is associated with the development of obesity and obesity-related disorders such as type 2 diabetes mellitus, metabolic syndrome, and non-alcoholic fatty liver disease. This article will review the current literature on gut microbiome and its impact on obesity and obesity-related disorders.<br><br>RECENT FINDINGS: An altered gut microbial composition in obesity and obesity-related disorders is associated with enhanced energy extraction from the non-digestible dietary carbohydrates, increased gut permeability, increased production of proinflammatory metabolites, such as lipopolysaccharides, resulting in systemic inflammation and insulin resistance. Gut microbiota modulation can be achieved either by dietary manipulation or by administration of probiotics, prebiotics, synbiotics, and/or fecal microbiota transplantation aiming at the improvement of the gut dysbiosis in obesity and metabolic disorders. Further clinical trials are required to better elucidate the dose, and frequency of these interventions and also their long-term impact on host metabolism.}, }
@article {pmid36468853, year = {2022}, author = {Zhang, B and Zhao, C and Zhang, X and Li, X and Zhang, Y and Liu, X and Yin, J and Li, X and Wang, J and Wang, S}, title = {An Elemental Diet Enriched in Amino Acids Alters the Gut Microbial Community and Prevents Colonic Mucus Degradation in Mice with Colitis.}, journal = {mSystems}, volume = {7}, number = {6}, pages = {e0088322}, pmid = {36468853}, issn = {2379-5077}, mesh = {Mice ; Humans ; Animals ; Amino Acids/adverse effects ; Expectorants/adverse effects ; *Colitis/chemically induced ; *Microbiota ; Bacteria ; Mucus/metabolism ; }, abstract = {The role of dietary amino acids or intact proteins in the progression of colitis remains controversial, and the mechanism involving gut microbes is unclear. Here, we investigated the effects of an elemental diet (ED) enriched in amino acids and a polymeric diet enriched in intact protein on the pathogenesis of dextran sulfate sodium (DSS)-induced colitis in mice. Our results showed that the ED induced remission of colitis in mice. Notably, ED treatment reduced the abundance of the mucolytic bacteria Akkermansia and Bacteroides, which was attributed to decreased colonic protein fermentation. Consistently, the activities of mucolytic enzymes were decreased, leading to protection against mucus layer degradation and microbial invasion. Fecal microbiota transplantation from ED-fed mice reshaped microbial ecology and alleviated intestinal inflammation in recipient mice. The ED failed to induce remission of colitis in pseudogermfree mice. Together, our results demonstrate the critical role of the gut microbiota in the prevention of colitis by an ED. IMPORTANCE The prevalence of inflammatory bowel disease is rapidly increasing and has become a global burden. Several specific amino acids have been shown to benefit mucosal healing and colitis remission. However, the role of amino acids or intact proteins in diets and enteral nutrition formulas is controversial, and the mechanisms involving gut microbes remain unclear. In this study, we investigated the effects of an elemental diet (ED) enriched in amino acids and a polymeric diet enriched in intact protein on the pathogenesis of colitis in mice. The underlying mechanisms were explored by utilizing fecal microbiota transplantation and pseudogermfree mice. ED treatment reduced the abundance of mucolytic bacteria, thereby protecting the mucus layer from microbial invasion and degradation. For the first time, we convincingly demonstrated the critical role of gut microbiota in the effects of the ED. This study may provide new insights into the gut microbiota-diet interaction and its role in human health.}, }
@article {pmid36468073, year = {2022}, author = {Yang, L and Li, W and Zhang, X and Tian, J and Ma, X and Han, L and Wei, H and Meng, W}, title = {The evaluation of different types fecal bacteria products for the treatment of recurrent Clostridium difficile associated diarrhea: A systematic review and network meta-analysis.}, journal = {Frontiers in surgery}, volume = {9}, number = {}, pages = {927970}, pmid = {36468073}, issn = {2296-875X}, abstract = {PURPOSE: To determine the efficacy of different types of fecal microbiota transplantation for the treatment of recurrent clostridium difficile associated diarrhea (RCDAD).<br><br>METHODS: We searched PubMed, Embase, The Cochrane Library, Web of Science, China Biomedical Medicine (CBM), China National Knowledge Infrastructure (CNKI) and WanFang database. We also tracked the references found in systematic reviews of RCDAD treated with fecal microbiota transplantation. We included randomized controlled trials (RCTs) comparing different types of fecal microbiota transplantation with other methods for the treatment of RCDAD. The search period was from the date of inception of this treatment method to January 16, 2022. Two reviewers independently screened the published literature, extracted the data and assessed the risk of bias. Systematic review and network meta-analysis were conducted using RevMan 5.4, Stata 16.0 and R 4.1.2 software.<br><br>RESULTS: Ten RCTs involving 765 patients were included in this network meta-analysis. The results showed that treatment with fresh fecal bacteria and frozen fecal bacteria were better than vancomycin, fresh vs. vancomycin [odds ratio, (OR)&#x2009;=&#x2009;8.98, 95% confidence interval (95% CI) (1.84, 43.92)], frozen vs. vancomycin [OR&#x2009;=&#x2009;7.44, 95% CI (1.39, 39.75)]. However, there were no statistically significant differences in cure rate [fresh vs. frozen: OR&#x2009;=&#x2009;1.21, 95% CI (0.22, 6.77); fresh vs. lyophilized, OR&#x2009;=&#x2009;1.95, 95% CI (0.20, 19.44); frozen vs. lyophilized, OR&#x2009;=&#x2009;1.62, 95% CI (0.30, 8.85)]. The Surface Under the Cumulative Ranking (SUCRA) indicated that fresh fecal bacteria were the best treatment for RCDAD.<br><br>CONCLUSIONS: Fresh fecal bacteria are the best treatment of RCDAD, frozen fecal bacteria and lyophilized fecal bacteria can achieve the same effect. Fecal microbiota transplantation is worthy of clinical and commercial application.}, }
@article {pmid36467356, year = {2022}, author = {Dong, YH and Hu, JJ and Deng, F and Chen, XD and Li, C and Liu, KX and Zhao, BC}, title = {Use of dexmedetomidine to alleviate intestinal ischemia-reperfusion injury via intestinal microbiota modulation in mice.}, journal = {Annals of translational medicine}, volume = {10}, number = {21}, pages = {1161}, pmid = {36467356}, issn = {2305-5839}, abstract = {BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a serious condition with unacceptable mortality rates. Our previous study revealed a protective effect of dexmedetomidine (DEX) on intestinal I/R injury, but its underlying mechanism remains unclear. Gut microbiota imbalance is associated with the progression of I/R injury. We hypothesized that DEX would attenuate intestinal I/R injury via modulating gut microbiota.<br><br>METHODS: An I/R injury model was established in C57BL/6 mice in the presence or absence of DEX preconditioning. Some mice were treated with antibiotics to deplete intestinal bacteria. Fecal microbiota transplantation (FMT) was performed by transplanting the feces of DEX-pretreated mice into a new batch of I/R mice. We analyzed the expression of Bacteroidetes and Firmicutes in feces, survival rate, and inflammatory cytokines.<br><br>RESULTS: DEX reversed I/R-induced bacterial abnormalities by increasing the ratio of Firmicutes to Bacteroidetes [DEX + I/R 3.02&#xb1;0.36 vs. normal saline (NS) + I/R 0.82&#xb1;0.15; 95% CI: 0.80-3.60; P<0.05] and was accompanied by increased 72-hour survival (0.40&#xb1;0.16 vs. 0.10&#xb1;0.09; P<0.05). The protective effect of DEX did not significantly differ from that of DEX + antibiotics. Furthermore, the bacteria of the DEX-pretreated mice decreased the release of inflammatory factors.<br><br>CONCLUSIONS: This study revealed that DEX can alleviate intestinal I/R injury through a microbiota-related mechanism, providing a potential avenue for the management of intestinal I/R injury.}, }
@article {pmid36467061, year = {2022}, author = {Wang, R and Liu, M and Ren, G and Luo, G and Wang, Z and Ge, Z and Pu, Q and Ren, W and Yang, S}, title = {Zhilong Huoxue Tongyu Capsules' Effects on ischemic stroke: An assessment using fecal 16S rRNA gene sequencing and untargeted serum metabolomics.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {1052110}, pmid = {36467061}, issn = {1663-9812}, abstract = {Zhilong Huoxue Tongyu capsule (ZHTC) is an effective traditional Chinese medicine compound for the treatment of ischemic stroke, which is widely used in clinical ischemic stroke patients. However, it is uncertain whether ZHTC affects ischemic stroke through gut microbiota and serum metabolites. In this study, a rat model of middle cerebral artery occlusion (MCAO) was prepared. By evaluating motor nerve function score, cerebral infarct size, brain tissue damage and intestinal barrier damage, it was found that ZHTC improved stroke-related symptoms in MCAO rats. Using 16S rRNA gene sequencing, fecal microbial transplantation (FMT), untargeted metabolomics, and spearman correlation analysis of gut microbiota and serum metabolites, we found that ZHTC can regulate the abundance of p_Firmicutes, p_Bacteroidota,p_Proteobacteria, g_Prevotella, and g_Lactobacillus, and regulated 23 differential metabolites. Spearman correlation analysis found that Arginine was positively correlated with p_Firmicutes, o_Clostridiales, c_Clostridia, and negatively correlated with p_Bacteroidetes, c_Bacteroidia,o_Bacteroidales; L-Lysine was negatively correlated with f_Christensenellaceae; L-methionine was positively correlated with o_Lactobacillales, f_Lactobacillaceae, and g_Lactobacillus. Altogether, this study shows for the first time that ZHTC can ameliorate ischemic stroke by modulating gut microbiota and metabolic disturbances. This lays the foundation for further revealing the causal relationship between ZHTC, gut dysbiosis, plasma metabolite levels and ischemic stroke, and provides a scientific explanation for the ameliorating effect of ZHTC on ischemic stroke.}, }
@article {pmid36466675, year = {2022}, author = {El Haddad, L and Mendoza, JF and Jobin, C}, title = {Bacteriophage-mediated manipulations of microbiota in gastrointestinal diseases.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1055427}, pmid = {36466675}, issn = {1664-302X}, support = {K01 AI166096/AI/NIAID NIH HHS/United States ; R01 DK073338/DK/NIDDK NIH HHS/United States ; R21 CA264927/CA/NCI NIH HHS/United States ; }, abstract = {Although some gastrointestinal diseases could be managed using various antibiotics regimen, this therapeutic approach lacks precision and damages the microbiota. Emerging literature suggests that phages may play a key role in restoring the gut microbiome balance and controlling disease progression either with exogenous phage intervention or filtered fecal transplantation or even engineered phages. In this review, we will discuss the current phage applications aiming at controlling the bacterial population and preventing infection, inflammation, and cancer progression in the context of gastrointestinal diseases.}, }
@article {pmid36466673, year = {2022}, author = {Wang, Y and Zhang, Z and Liu, B and Zhang, C and Zhao, J and Li, X and Chen, L}, title = {A study on the method and effect of the construction of a humanized mouse model of fecal microbiota transplantation.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1031758}, pmid = {36466673}, issn = {1664-302X}, abstract = {The gestation period is critical for the health of the mother and fetus. Malnutrition or over nutrition during pregnancy may cause gestational diseases that can result in adverse pregnancy outcomes. Fecal microbiota transplantation (FMT) can be used to re-establish new gut microbiota to treat a variety of diseases and construct a model to investigate the nutritional health during pregnancy. Therefore, this study investigated whether human-derived gut microbiota during pregnancy could colonize the intestines of mice. Moreover, we determined the time and method of intervention for FMT. Based on this information, a humanized mouse model of FMT was constructed to simulate the human intestinal microecology during pregnancy, and serve as a useful animal model for the study of nutritional health and disease during pregnancy. Germ-free (GF) and specific pathogen free (SPF) C57BL/6J mice were selected for humanized gestational FMT and the transplantation outcomes were evaluated. The results demonstrated that the gestational intestinal microbiota colonized the intestines of mice, allowing researchers to construct a humanized mouse model of gestational FMT. The main intestinal flora of the gestational period were transplanted into GF mice, with the gestational flora being similar to the flora of GF mice after transplantation. However, antibiotics could not eliminate the original microbial flora in SPF mice, and the flora was complex and variable after FMT with little increase in abundance. Background flora had a significant impact on the outcomes assessment. The results were better in GF mice than in SPF mice, and after microbiota transplantation, a superior effect was observed on day 21 compared to days 7 and 14.}, }
@article {pmid36466655, year = {2022}, author = {Wei, W and Wang, S and Xu, C and Zhou, X and Lian, X and He, L and Li, K}, title = {Gut microbiota, pathogenic proteins and neurodegenerative diseases.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {959856}, pmid = {36466655}, issn = {1664-302X}, abstract = {As the world's population ages, neurodegenerative diseases (NDs) have brought a great burden to the world. However, effective treatment measures have not been found to alleviate the occurrence and development of NDs. Abnormal accumulation of pathogenic proteins is an important cause of NDs. Therefore, effective inhibition of the accumulation of pathogenic proteins has become a priority. As the second brain of human, the gut plays an important role in regulate emotion and cognition functions. Recent studies have reported that the disturbance of gut microbiota (GM) is closely related to accumulation of pathogenic proteins in NDs. On the one hand, pathogenic proteins directly produced by GM are transmitted from the gut to the central center via vagus nerve. On the other hand, The harmful substances produced by GM enter the peripheral circulation through intestinal barrier and cause inflammation, or cross the blood-brain barrier into the central center to cause inflammation, and cytokines produced by the central center cause the production of pathogenic proteins. These pathogenic proteins can produced by the above two aspects can cause the activation of central microglia and further lead to NDs development. In addition, certain GM and metabolites have been shown to have neuroprotective effects. Therefore, modulating GM may be a potential clinical therapeutic approach for NDs. In this review, we summarized the possible mechanism of NDs caused by abnormal accumulation of pathogenic proteins mediated by GM to induce the activation of central microglia, cause central inflammation and explore the therapeutic potential of dietary therapy and fecal microbiota transplantation (FMT) in NDs.}, }
@article {pmid36466637, year = {2022}, author = {Elokil, AA and Chen, W and Mahrose, K and Elattrouny, MM and Abouelezz, KFM and Ahmad, HI and Liu, HZ and Elolimy, AA and Mandouh, MI and Abdelatty, AM and Li, S}, title = {Early life microbiota transplantation from highly feed-efficient broiler improved weight gain by reshaping the gut microbiota in laying chicken.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1022783}, pmid = {36466637}, issn = {1664-302X}, abstract = {Starting phase of laying chicken life is the building stone for rearing and production stages. Since, fecal microbial transplantation (FMT) regulates the gut microbial diversity and affects the productive performance of the bird. The aim of this study is to evaluate the effect of FMT from feed-efficient broiler chicken could program the diversity of gut microbiota and growth of recipient native slow growing egg-laying chicks. For this, a total of 150 (one-day-old) Jing Hong chicks were randomly assigned into two groups, each group consisted of 5 replicates (n = 15 bird/ replicate). The control group (CON) and FMT recipient birds (FMT) fed on basal diet, the FMT group received an oral daily dose of FMT prepared from Cobb-500 chickens. The FMT performed from the 1d to 28d of age, through the experimental period, feed intake and body weight were recorded weekly. At the end of a 28-day trial, carcass traits were assessed and cecal samples were collected for microbiome assessment via 16S rRNA-based metagenomic analysis to characterize the diversity and functions of microbial communities. The data were statistically analyzed using R software. Body weight and body weight gain increased, and FCR decreased (p = 0.01) in FMT group. The relative abundance of Firmicutes and the Firmicutes/Bacteroidetes (F/B) ratio were increased due to FMT administration (p = 0.01). A higher relative abundance of Lactobacillus, Lactococcus, and Bifidobacterium were presented in the FMT group. Meanwhile, Enterococcus, Helicobacter, and Bacteroides were more abundant in the CON group (p < 0.01). Kyoto encyclopedia of genes and genomes (KEGG) pathways for microbial functions regarding amino acid metabolism, secondary metabolites biosynthesis, carbohydrate metabolism, energy metabolism, and enzyme families, cofactors, and vitamins were significantly annotated in the FMT group. Overall, FMT administration from the donor of highly feed-efficient broilers improved weight gain by reshaping a distinct gut microbiome, which may be related to the metabolism and health in the recipients laying chicks, providing new insight on the application of the FMT technique for early life programming of laying chickens.}, }
@article {pmid36461391, year = {2022}, author = {Liu, X and Zhang, Y and Li, W and Yin, J and Zhang, B and Wang, J and Wang, S}, title = {Differential responses on gut microbiota and microbial metabolome of 2'-fucosyllactose and galactooligosaccharide against DSS-induced colitis.}, journal = {Food research international (Ottawa, Ont.)}, volume = {162}, number = {Pt B}, pages = {112072}, doi = {10.1016/j.foodres.2022.112072}, pmid = {36461391}, issn = {1873-7145}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Prebiotics ; *Colitis/chemically induced ; Metabolome ; }, abstract = {Prebiotics are effective in modulating gut microbiota and may further benefit colitis remission. 2'-fucosyllactose (2'FL) and galactooligosaccharide (GOS) are the main prebiotics in human and animal milk, respectively. This study aimed to investigate the colitis-preventing effects of 2'FL and GOS, and explore the underlying mechanisms involving the gut microbiota. The chronic colitis was induced by 1.5 % dextran sulfate sodium (DSS) for 4 consecutive cycles and manifested as aggravation of colitis symptoms, gut barrier disruption, and colonic inflammation. We found that 2'FL was more effective than GOS against colitis at the same dosage (500 mg/kg bw). 2'FL and GOS have a differential response on gut microbiota, reflecting the inhibition of Romboutsia and the enrichment of Akkermansia, Bifidobacterium, Faecalibaculum, and unclassified_f_Lachnosipiaceae. In addition, the differential response on microbial metabolome was reflected in the elevation of secondary bile acids, which activated Takeda G protein-coupled receptor 5 (TGR5) and further suppressed the nuclear factor-κB (NF-κB) pathway. Furthermore, fecal bacterial transplantation confirmed the critical role of gut microbiota in the prevention of colitis by 2'FL and GOS. Overall, microbiota and microbial metabolites are essential parts of 2'FL and GOS against colitis, and their differential responses may account for different effects in alleviating colitis.}, }
@article {pmid36461273, year = {2022}, author = {Tang, Q and Wang, C and Jin, G and Li, Y and Hou, H and Wang, X and Guo, Q and Liu, T and Wang, S and Dai, X and Wang, B and Cao, H}, title = {Early life dietary emulsifier exposure predisposes the offspring to obesity through gut microbiota-FXR axis.}, journal = {Food research international (Ottawa, Ont.)}, volume = {162}, number = {Pt A}, pages = {111921}, doi = {10.1016/j.foodres.2022.111921}, pmid = {36461273}, issn = {1873-7145}, mesh = {Female ; Pregnancy ; Mice ; Animals ; *Gastrointestinal Microbiome ; Dysbiosis ; Mice, Inbred C57BL ; Obesity ; Emulsifying Agents/adverse effects ; Bile Acids and Salts ; Polysorbates ; Inflammation ; }, abstract = {The prevalence of obesity is increasing rapidly around the world, and there is growing evidence that obesity is closely related to diet and gut microbiota. Early life adverse exposures have profound effects on gut microbiota. However, the effects of maternal emulsifier polysorbate 80 (P80) exposure in early life on obesity of offspring remains unclear. Female C57BL/6 mice were free access to water containing 1 % P80 during pregnancy and lactation to investigate the effects of maternal P80 exposure on gut microbiota and obesity susceptibility of offspring, while bile acid composition and the FGF15-FXR axis were also analyzed. Maternal P80 exposure significantly impaired intestinal development and barrier function and increased intestinal low-grade inflammation in offspring mice. Maternal P80 exposure led to gut dysbiosis in offspring at 3 weeks of age, which was characterized by increased potentially harmful bacteria, Prevotella, Helicobacter and Ruminococcus and Mucin degrading bacteria, Akkermansia. Interestingly, mice transplanted with the fecal microbiota of offspring exposed to maternal P80 showed more serious intestinal barrier impairment and increased low-grade inflammation than that received microbiota of offspring fed with normal diet. After a high-fat diet, Maternal P80 exposed offspring showed more severe in gut dysbiosis and obesity, accompanied by alternation in bile acid profile and up regulation of the FXR-FGF15 axis. Conclusively, early life emulsifier exposure predisposes the offspring to obesity through gut microbiota-FXR axis. The findings will provide new insights into effects of P80 on health.}, }
@article {pmid36457852, year = {2022}, author = {Wu, L and Lu, XJ and Lin, DJ and Chen, WJ and Xue, XY and Liu, T and Xu, JT and Xie, YT and Li, MQ and Lin, WY and Zhang, Q and Wu, QP and He, XX}, title = {Washed microbiota transplantation improves patients with metabolic syndrome in South China.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1044957}, pmid = {36457852}, issn = {2235-2988}, mesh = {Humans ; *Metabolic Syndrome/therapy ; Cholesterol, LDL ; RNA, Ribosomal, 16S/genetics ; Retrospective Studies ; China ; Triglycerides ; *Atherosclerosis ; *Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Metabolic syndrome (MS) is a growing public health problem worldwide. The clinical impact of fecal microbiota transplantation (FMT) from healthy donors in MS patients is unclear, especially in southern Chinese populations. This study aimed to investigate the effect of washed microbiota transplantation (WMT) in MS patients in southern China.<br><br>METHODS: The clinical data of patients with different indications receiving 1-3 courses of WMT were retrospectively collected. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared, such as fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c)), high-density lipoprotein cholesterol (HDL-c), non-high-density lipoprotein (non-HDL-c), systolic blood pressure (SBP), diastolic blood pressure (DBP), etc. At the same time, comprehensive efficacy evaluation and atherosclerotic cardiovascular disease (ASCVD) grade assessment were performed on MS patients. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of MS patients before and after transplantation.<br><br>RESULTS: A total of 237 patients were included, including 42 in the MS group and 195 in the non-MS group. For MS patients, WMT significantly improved the comprehensive efficacy of MS in short term 40.48% (p<0.001), medium term 36.00% (p=0.003), and long term 46.15% (p=0.020). Short-term significantly reduced FBG (p=0.023), TG (p=0.030), SBP (p=0.026) and BMI (p=0.031), and increased HDL-c (p=0.036). The medium term had a significant reduction in FBG (p=0.048), TC (p=0.022), LDL-c (p=0.043), non-HDL-c (p=0.024) and BMI (p=0.048). WMT had a significant short term (p=0.029) and medium term (p=0.011) ASCVD downgrading effect in the high-risk group of MS patients. WMT improved gut microbiota in MS patients.<br><br>CONCLUSION: WMT had a significant improvement effect on MS patients and a significant downgrade effect on ASCVD risk in the high-risk group of patients with MS. WMT could restore gut microbiota homeostasis in MS patients. Therefore, the regulation of gut microbiota by WMT may provide a new clinical approach for the treatment of MS.}, }
@article {pmid36456838, year = {2023}, author = {Liu, H and Kang, X and Yang, X and Yang, H and Kuang, X and Ren, P and Yan, H and Shen, X and Kang, Y and Li, L and Wang, X and Guo, L and Tong, M and Fan, W}, title = {Compound Probiotic Ameliorates Acute Alcoholic Liver Disease in Mice by Modulating Gut Microbiota and Maintaining Intestinal Barrier.}, journal = {Probiotics and antimicrobial proteins}, volume = {15}, number = {1}, pages = {185-201}, pmid = {36456838}, issn = {1867-1314}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Dysbiosis/therapy ; *Chemical and Drug Induced Liver Injury, Chronic/complications ; *Liver Diseases, Alcoholic/drug therapy ; *Probiotics ; Ethanol ; }, abstract = {Alcoholic liver disease (ALD) is a worldwide health threaten lack of effective treatment. Gut dysbiosis and concomitant augmented intestinal permeability are strongly implicated in the pathogenesis and progression of ALD. Research on the protective effect of probiotics on ALD is limited, and more effective intestinal microecological regulators and the related mechanisms still need to be further explored. In the present study, the protective effects and mechanisms of a compound probiotic against acute alcohol-induced liver injury in vivo were explod. It was showed that the compound probiotic ameliorated liver injury in acute ALD mice and stabilized the levels of ALT, AST, and TG in serum. The compound probiotic reversed acute alcohol-induced gut dysbiosis and maintained the intestinal barrier integrity by upregulating the production of mucus and the expression of tight junction (TJ) proteins and thus reduced LPS level in liver. Meanwhile, the compound probiotic reduced inflammation level by inhibiting TLR4/NF-κB signaling pathway and suppressed oxidative stress level in liver. Furthermore, the compound probiotic alleviated liver lipid accumulation by regulating fatty acid metabolism-associated genes and AMPK-PPARα signaling pathway. Noteworthy, fecal microbiota transplantation (FMT) realized comparable protective effect with that of compound probiotic. In conclusion, present study demonstrates the beneficial effects and underlying mechanism of the compound probiotic against acute alcohol-induced liver injury. It provides clues for development of novel strategy for treatment of ALD.}, }
@article {pmid36454023, year = {2023}, author = {Cumpelik, A and Cody, E and Yu, SM and Grasset, EK and Dominguez-Sola, D and Cerutti, A and Heeger, PS}, title = {Cutting Edge: Neutrophil Complement Receptor Signaling Is Required for BAFF-Dependent Humoral Responses in Mice.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {210}, number = {1}, pages = {19-23}, pmid = {36454023}, issn = {1550-6606}, support = {R01 AI141434/AI/NIAID NIH HHS/United States ; T32 AI078892/AI/NIAID NIH HHS/United States ; T32 DK007757/DK/NIDDK NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Neutrophils ; *B-Lymphocytes ; Complement System Proteins/metabolism ; Mice, Knockout ; Receptors, Complement/metabolism ; Immunoglobulin A ; }, abstract = {T cell-independent (TI) B cell responses to nonprotein Ags involve multiple cues from the innate immune system. Neutrophils express complement receptors and activated neutrophils can release BAFF, but mechanisms effectively linking neutrophil activation to TI B cell responses are incompletely understood. Using germline and conditional knockout mice, we found that TI humoral responses involve alternative pathway complement activation and neutrophil-expressed C3a and C5a receptors (C3aR1/C5aR1) that promote BAFF-dependent B1 cell expansion and TI Ab production. Conditional absence of C3aR1/C5aR1 on neutrophils lowered serum BAFF levels, led to fewer Peyer's patch germinal center B cells, reduced germinal center B cells IgA class-switching, and lowered fecal IgA levels. Together, the results indicate that sequential activation of complement on neutrophils crucially supports humoral TI and mucosal IgA responses through upregulating neutrophil production of BAFF.}, }
@article {pmid36451382, year = {2022}, author = {Chen, Q and Zhang, Z and Bei, S and Wang, X and Zhu, Y}, title = {Efficacy of oral fecal microbiota transplantation in recurrent bowel disease: A protocol for systematic review and meta-analysis.}, journal = {Medicine}, volume = {101}, number = {47}, pages = {e31477}, pmid = {36451382}, issn = {1536-5964}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Irritable Bowel Syndrome/therapy ; Quality of Life ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; Chronic Disease ; *Inflammatory Bowel Diseases/therapy ; }, abstract = {BACKGROUND: Recurrent bowel disease (RBD) refers to the chronic, recurrent intestinal diseases, including recurrent Clostridium Difficile Infection (rCDI), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), etc., these diseases have similar clinical characteristics, that is, abdominal pain, diarrhea, repeated attacks, prolonged recovery, etc. Clinically, there are relevant reports on the use of oral capsule fecal microbiota transplantation (oFMT) to treat RBD. However, both the advantages and disadvantages of clinical efficacy have been reported; there are some contradictions, the study sample size is too small, and the purpose of this systematic review was to evaluate the efficacy and safety of oral capsule fecal microbiota transplantation in the treatment of RBD.<br><br>METHODS: This systematic review will include articles identified through electronic searches of the PubMed, EMbase, and Cochrane Library. From inception to July 1, 2022. Two reviewers will independently search the database to conduct data extraction and assessment of study quality. Based on heterogeneity tests, data will be integrated using fixed or random effect models. RevMan V.5.4 will be used for data analysis. The results are expressed as the risk ratio of dichotomous data and the mean difference of continuous data.<br><br>RESULTS: We analyzed the clinical remission or cure rate, IBS-SSS, quality of life, anxiety, depression, total adverse effects, and total severe adverse effects (TSAE) in patients with RBD.<br><br>CONCLUSION: This systematic review evaluated the efficacy and safety of oFMT in the treatment of RBD to provide more comprehensive evidence.}, }
@article {pmid36451045, year = {2023}, author = {Thomas, AR and Liu, C and Tong, YT and Tan, D and Altan, M and Siddiqui, BA and Shatila, M and Khan, A and Thomas, AS and Wang, Y}, title = {Characteristics and outcomes of cancer patients with pre-existing microscopic colitis after exposure to PD-1 and PD-L1 inhibitors.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {8}, pages = {5429-5436}, pmid = {36451045}, issn = {1432-1335}, mesh = {Humans ; Immune Checkpoint Inhibitors/adverse effects ; Programmed Cell Death 1 Receptor ; Retrospective Studies ; *Antineoplastic Agents, Immunological/adverse effects ; *Colitis/chemically induced/drug therapy ; *Lung Neoplasms/drug therapy ; *Colitis, Microscopic/chemically induced/drug therapy ; }, abstract = {PURPOSE: Immune checkpoint inhibitors (ICIs) are frequently associated with adverse events, often affecting the gastrointestinal tract. We conducted this study to determine the characteristics and outcomes of cancer patients with pre-existing microscopic colitis (MC) who underwent ICI treatment.<br><br>METHODS: In this retrospective study, we identified 10 patients with pre-existing MC who received ICIs at our center 01/2010-06/2020. Clinical characteristics and disease outcomes were recorded.<br><br>RESULTS: Of 124 screened patients with MC before ICI exposure, 10 had sufficient data to be included in the study. Melanoma (40%) and lung cancer (30%) were the most prevalent cancer types, with 70% of stage IV cancer. Patients received either anti-programmed death 1 regimen (8, 80%) or anti-programmed death ligand 1 agent (2, 20%). Six patients (60%) had collagenous colitis, and 4 (40%) had lymphocytic colitis. The median time from MC diagnosis to ICI initiation was 4&#xa0;years, with 1 patient on budesonide within 2&#xa0;months of ICI initiation. Eight patients (80%) developed colitis exacerbations after ICI &#xa0;and required selective immunosuppression. One patient received a compassionate-use fecal transplantation. The median time from ICI to colitis exacerbation was 14&#xa0;days, with 40% and 50% of patients experiencing grade 3 diarrhea and grade 2 colitis, respectively, leading to hospitalization in 3 patients. Six patients received steroids and vedolizumab with no colitis recurrence. Of 8 patients who had colitis exacerbation, 6 resumed ICI therapy afterward; with 5 receiving concomitant vedolizumab for secondary prophylaxis.<br><br>CONCLUSION: Our findings suggest that ICI exposure increases the risk of exacerbation of underlying colitis necessitating and responding to potent immunosuppression therapy.}, }
@article {pmid36450880, year = {2022}, author = {Xiao, L and Zhou, Y and Bokoliya, S and Lin, Q and Hurley, M}, title = {Bone loss is ameliorated by fecal microbiota transplantation through SCFA/GPR41/ IGF1 pathway in sickle cell disease mice.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {20638}, pmid = {36450880}, issn = {2045-2322}, support = {R56 HL147048/HL/NHLBI NIH HHS/United States ; }, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation ; Insulin-Like Growth Factor I ; *Bone Diseases, Metabolic ; *Anemia, Sickle Cell/therapy ; Feces ; }, abstract = {Bone loss is common in sickle cell disease (SCD), but the molecular mechanisms is unclear. Serum insulin-like growth factor 1 (IGF1) was low in SCD subjects and SCD mice. To determine if decreased IGF1 associated with low bone mass in SCD is due to reduced SCFA production by gut microbiota, we performed reciprocal fecal microbiota transplantation (FMT) between healthy control (Ctrl) and SCD mice. uCT and histomorphometry analysis of femur showed decreased bone volume/total volume (BV/TV), trabecular number (Tb.N), osteoblast surface/bone surface (Ob.S/BS), mineralizing surface/ bone surface (MS/BS), inter-label thickness (Ir.L.Th) in SCD mice were significantly improved after receiving Ctrl feces. Bone formation genes Alp, Col1, Runx2, and Dmp1 from SCD mice were significantly decreased and were rescued after FMT from Ctrl feces. Transplantation of Ctrl feces increased the butyrate, valerate, and propionate levels in cecal content of SCD mice. Decreased G-coupled protein receptors 41 and 43 (GPR41 and GPR43) mRNA in tibia and lower IGF1 in bone and serum of SCD mice were partially restored after FMT from Ctrl feces. These data indicate that the healthy gut microbiota of Ctrl mice is protective for SCD bone loss through regulating IGF1 in response to impaired bacterial metabolites SCFAs.}, }
@article {pmid36450285, year = {2023}, author = {Ousey, J and Boktor, JC and Mazmanian, SK}, title = {Gut microbiota suppress feeding induced by palatable foods.}, journal = {Current biology : CB}, volume = {33}, number = {1}, pages = {147-157.e7}, pmid = {36450285}, issn = {1879-0445}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Feeding Behavior/physiology ; Food ; Sucrose ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Feeding behaviors depend on intrinsic and extrinsic factors including genetics, food palatability, and the environment.[1][,][2][,][3][,][4][,][5] The gut microbiota is a major environmental contributor to host physiology and impacts feeding behavior.[6][,][7][,][8][,][9][,][10][,][11][,][12] Here, we explored the hypothesis that gut bacteria influence behavioral responses to palatable foods and reveal that antibiotic depletion (ABX) of the gut microbiota in mice results in overconsumption of several palatable foods with conserved effects on feeding dynamics. Gut microbiota restoration via fecal transplant into ABX mice is sufficient to rescue overconsumption of high-sucrose pellets. Operant conditioning tests found that ABX mice exhibit intensified motivation to pursue high-sucrose rewards. Accordingly, neuronal activity in mesolimbic brain regions, which have been linked with motivation and reward-seeking behavior,[3] was elevated in ABX mice after consumption of high-sucrose pellets. Differential antibiotic treatment and functional microbiota transplants identified specific gut bacterial taxa from the family S24-7 and the genus Lactobacillus whose abundances associate with suppression of high-sucrose pellet consumption. Indeed, colonization of mice with S24-7 and Lactobacillus johnsonii was sufficient to reduce overconsumption of high-sucrose pellets in an antibiotic-induced model of binge eating. These results demonstrate that extrinsic influences from the gut microbiota can suppress the behavioral response toward palatable foods in mice.}, }
@article {pmid36447381, year = {2023}, author = {Sever, A and Ben Zvi, H and Melamed, SB and Sachs, N and Krause, I and Bilavsky, E}, title = {Clinical impact of biofire gastrointestinal panel testing for hospitalised children with acute gastroenteritis.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {112}, number = {3}, pages = {505-509}, doi = {10.1111/apa.16610}, pmid = {36447381}, issn = {1651-2227}, mesh = {Child ; Humans ; Retrospective Studies ; Child, Hospitalized ; *Cryptosporidiosis ; Feces ; *Cryptosporidium ; *Gastroenteritis/diagnosis ; Diarrhea/etiology ; }, abstract = {AIM: To investigate the clinical impact of BioFire FilmArray Gastrointestinal Panel (FGP) testing in real-life diarrhoeal episodes of hospitalised paediatric patients.<br><br>METHODS: Children hospitalised between October 2018 and September 2020 for whom stool specimens for FGP were submitted at the clinician's discretion were retrospectively observed. For each episode, demographics, clinical information and stool tests were collected.<br><br>RESULTS: The clinical impact for each case was evaluated by changing the antibiotic prescription, following the result of the FGP testing. Out of 140 diarrhoeal episodes, 25 pathogens were found in 24 cases using conventional methods, whereas, FGP testing identified 75 pathogens in 56 cases (p&#xa0;<&#x2009;0.05). The pathogens more frequently identified by FGP testing were Campylobacter, Shigella, Rotavirus, Giardia lamblia and Cryptosporidium. The clinical impact of FGP testing was observed in 17/140 (12%) diarrhoeal episodes, and higher rates in previously healthy (19%) and solid organ-transplanted children (15%).<br><br>CONCLUSION: We found that using FGP testing for hospitalised children with diarrhoeal episodes could increase pathogen identification and impact clinical decisions, especially in healthy and transplant patients.}, }
@article {pmid36444412, year = {2022}, author = {Karakavuk, T and Gül, C and Karakavuk, M and Gül, A and Erkunt Alak, S and Can, H and Ün, C and Döşkaya, M and Gürüz, AY and Değirmenci Döşkaya, A}, title = {Biotechnological Based Recombinant Protein Vaccines Developed Against Toxoplasmosis.}, journal = {Turkiye parazitolojii dergisi}, volume = {46}, number = {4}, pages = {342-357}, doi = {10.4274/tpd.galenos.2022.41636}, pmid = {36444412}, issn = {2146-3077}, mesh = {Humans ; Female ; Pregnancy ; Sheep ; Animals ; Biotechnology ; *Toxoplasma/genetics ; Goats ; Animals, Domestic ; *Toxoplasmosis ; Recombinant Proteins ; }, abstract = {Toxoplasma gondii (T. gondii) that can infect most warm-blooded animals and humans, is an obligate intracellular apicomplexan parasite with a wide host range. About one-third of the world's population is infected with this parasite. While toxoplasmosis progresses asymptomatically in individuals with a strong immune system, it can cause serious clinical manifestations and death in immunocompromised individuals. The parasite is transmitted to humans through the consumption of water and food contaminated with cat feces, as well as raw or undercooked animal products, congenital infection and blood/organ transplantation. Additionally, T. gondii is often observed in farm animals such as sheep and goats. Clinical manifestations and abortions caused by T. gondii in sheep and goats lead to enormous economic loss worldwide. There is a commercial vaccine against T. gondii, called Toxovax (MSD, New Zealand) that can only be used in sheep. For these reasons, there is a need for innovative T. gondii vaccine that is harmless, easily produced, which can prevent losses and be used in all living things. Advances in immunology, molecular biology, genetic, biotechnology and proteomics bring new perspectives to vaccine studies. Studies in innovative vaccine studies against T. gondii have accelerated with the discovery of new antigens by in vitro screenings, and bioinformatic analyzes, the use of various expression systems and new adjuvant types. Recombinant protein vaccines are biotechnological vaccines that are frequently preferred due to their rapid and easy production in various expression systems, availability of very and high purity products, ease of manipulation and stimulation of both cellular and humoral immune responses. Recombinant protein vaccines, developed by biotechnological methods, are promising tools for providing a protective immune response against toxoplasmosis. In this review, an overview of the parasite complex life cycle, its pathogenesis, humoral and cellular immune responses in the host, and recombinant protein vaccine studies developed against the parasite are presented.}, }
@article {pmid36442762, year = {2023}, author = {Liu, C and Song, C and Wang, Y and Xiao, Y and Zhou, Z and Cao, G and Sun, X and Liu, Y}, title = {Deep-fried Atractylodes lancea rhizome alleviates spleen deficiency diarrhea-induced short-chain fatty acid metabolic disorder in mice by remodeling the intestinal flora.}, journal = {Journal of ethnopharmacology}, volume = {303}, number = {}, pages = {115967}, doi = {10.1016/j.jep.2022.115967}, pmid = {36442762}, issn = {1872-7573}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; *Atractylodes/chemistry ; Antidiarrheals/pharmacology ; Rhizome ; Diarrhea/drug therapy/metabolism ; *Splenic Diseases/drug therapy ; Fatty Acids, Volatile/metabolism ; Colon/metabolism ; Disease Models, Animal ; *Metabolic Diseases/drug therapy ; Mice, Inbred C57BL ; Dextran Sulfate ; }, abstract = {Atractylodes lancea (Thunb.) DC. is a Chinese herb that has been commonly used to treat spleen-deficiency diarrhea (SDD) in China for over a thousand years. However, the underlying mechanism of its antidiarrheal activity is not fully understood.<br><br>AIM OF THE STUDY: The antidiarrheal effects of the ethanol extract of deep-fried A. lancea rhizome (EEDAR) due to spleen deficiency induced by folium sennae (SE) were determined on the regulation of the short-chain fatty acid (SCFA) metabonomics induced by the intestinal flora.<br><br>MATERIALS AND METHODS: The effects of EEDAR on a SE-induced mouse model of SDD were evaluated by monitoring the animal weight, fecal water content, diarrhea-grade rating, goblet cell loss, and pathological changes in the colon. The expression of inflammatory factors (tumor necrosis factor [TNF]-&#x3b1;, interleukin [IL]-1&#x3b2;, IL-6, IL-10), aquaporins (AQP3, AQP4, and AQP8), and tight junction markers (ZO-1, occludin, claudin-1) in colon tissues were determined using quantitative polymerase chain reaction and western blotting. SCFA metabonomics in the feces of mice treated with EEDAR was evaluated using gas chromatography-mass spectrometry. Furthermore, 16S rDNA sequencing was used to determine the effect of EEDAR on the intestinal flora of SDD mice, and fecal microbiota transplantation (FMT) was used to confirm whether the intestinal flora was essential for the anti-SDD effect of EEDAR.<br><br>RESULTS: Treatment with EEDAR significantly improved the symptoms of mice with SDD by inhibiting the loss of colonic cup cells, alleviating colitis, and promoting the expression of AQPs and tight junction markers. More importantly, the effect of EEDAR on the increase of SCFA content in mice with SDD was closely related to the gut microbiota composition. EEDAR intervention did not significantly improve intestinal inflammation or the barrier of germ-free SDD mice, but FMT was effective.<br><br>CONCLUSION: EEDAR alleviated SE-induced SDD in mice, as well as the induced SCFA disorder by regulating the imbalance of the intestinal microbiota.}, }
@article {pmid36441203, year = {2022}, author = {Bishop, EJ and Tiruvoipati, R}, title = {Management of Clostridioides difficile infection in adults and challenges in clinical practice: review and comparison of current IDSA/SHEA, ESCMID and ASID guidelines.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {78}, number = {1}, pages = {21-30}, pmid = {36441203}, issn = {1460-2091}, mesh = {Adult ; Humans ; Vancomycin/therapeutic use ; Fidaxomicin/therapeutic use ; Metronidazole/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/drug therapy/prevention &amp; control ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Clostridioides difficile infection (CDI) remains a significant clinical challenge both in the management of severe and severe-complicated disease and the prevention of recurrence. Guidelines released by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America (IDSA/SHEA) and ESCMID had some consensus as well as some discrepancies in disease severity classification and treatment recommendations. We review and compare the key clinical strategies from updated IDSA/SHEA, ESCMID and current Australasian guidelines for CDI management in adults and discuss relevant issues for clinicians, particularly in the management of severe-complicated infection. Updated IDSA/SHEA and ESCMID guidelines now reflect the increased efficacy of fidaxomicin in preventing recurrence and have both promoted fidaxomicin to first-line therapy with an initial CDI episode in both non-severe and severe disease and endorsed the role of bezlotoxumab in the prevention of recurrent infection. Vancomycin remains acceptable therapy and metronidazole is not preferred. For severe-complicated infection the IDSA/SHEA recommends high-dose oral ± rectal vancomycin and IV metronidazole, whilst in an important development, ESCMID has endorsed fidaxomicin and tigecycline as part of combination anti-CDI therapy, for the first time. The role of faecal microbiota transplantation (FMT) in second CDI recurrence is now clearer, but timing and mode of FMT in severe-complicated refractory disease still requires further study.}, }
@article {pmid36440358, year = {2022}, author = {Zhang, H and Duan, Y and Cai, F and Cao, D and Wang, L and Qiao, Z and Hong, Q and Li, N and Zheng, Y and Su, M and Liu, Z and Zhu, B}, title = {Next-Generation Probiotics: Microflora Intervention to Human Diseases.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {5633403}, pmid = {36440358}, issn = {2314-6141}, mesh = {Humans ; *Gastrointestinal Microbiome ; Ecosystem ; *Probiotics/therapeutic use ; Intestines ; }, abstract = {With the development of human genome sequencing and techniques such as intestinal microbial culture and fecal microbial transplantation, newly discovered microorganisms have been isolated, cultured, and researched. Consequently, many beneficial probiotics have emerged as next-generation probiotics (NGPs). Currently, "safety," "individualized treatment," and "internal interaction within the flora" are requirements of a potential NGPs. Furthermore, in the complex ecosystem of humans and microbes, it is challenging to identify the relationship between specific strains, specific flora, and hosts to warrant a therapeutic intervention in case of a disease. Thus, this review focuses on the progress made in NGPs and human health research by elucidating the limitations of traditional probiotics; summarizing the functions and strengths of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis, Eubacterium hallii, and Roseburia spp. as NGPs; and determining the role of their intervention in treatment of certain diseases. Finally, we aim to provide a reference for developing new probiotics in the future.}, }
@article {pmid36439840, year = {2022}, author = {Li, Z and Ke, H and Wang, Y and Chen, S and Liu, X and Lin, Q and Wang, P and Chen, Y}, title = {Global trends in Akkermansia muciniphila research: A bibliometric visualization.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1037708}, pmid = {36439840}, issn = {1664-302X}, abstract = {BACKGROUND: Akkermansia muciniphila is a member of the gut microbiome, using mucin as sources of carbon, nitrogen, and energy. Since the first discovery of this unique bacterium in 2004, A. muciniphila has been extensively studied. It is considered a promising "next-generation beneficial microbe." The purpose of this paper is to sort out the research status and summarize the hotspots through bibliometric analysis of the publications of A. muciniphila.<br><br>METHODS: The publications about A. muciniphila from January 2004 to February 2022 were obtained from the Web of Science Core Collection. Visualization analyses were performed using three bibliometric tools and GraphPad Prism.<br><br>RESULTS: A total of 1,478 published documents were analyzed. Annual publication number grew from 1 in 2004 to 336 in 2021, with China being the leading producer (33.36%). De Vos, Willem M was the most productive author with the highest H-index (documents&#x2009;=&#x2009;56, H-index&#x2009;=&#x2009;37), followed by Cani, Patrice D (documents&#x2009;=&#x2009;35, H-index&#x2009;=&#x2009;25). And Scientific Reports published the most papers. PNAS was the keystone taxa in this field, with high betweenness centrality (0.11) and high frequency. The keywords with high frequency in recent years include: oxidative stress, diet, metformin, fecal microbiota transplantation, short-chain fatty acids, polyphenols, microbiota metabolites and so on. The keyword "oxidative stress" was observed to be increasing in frequency recently.<br><br>CONCLUSION: Over time, the scope of the research on the clinical uses of A. muciniphila has gradually increased, and was gradually deepened and developed toward a more precise level. A. muciniphila is likely to remain a research hotspot in the foreseeable future and may contribute to human health.}, }
@article {pmid36439220, year = {2022}, author = {Zhang, F and Yang, P and Chen, Y and Wang, R and Liu, B and Wang, J and Yuan, M and Zhang, L}, title = {Bibliometric and visual analysis of fecal microbiota transplantation research from 2012 to 2021.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1057492}, pmid = {36439220}, issn = {2235-2988}, mesh = {Humans ; Fecal Microbiota Transplantation ; Bibliometrics ; *Enterocolitis, Pseudomembranous ; *Gastrointestinal Microbiome ; Chlorhexidine ; *Dermatitis ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging therapy for diseases associated with intestinal flora imbalance that has attracted increasing attention in recent years. This study aims to provide an overview of research trends in the field, and act as a reference point for future scientific research by analyzing the state of current research, identifying hotspots, and potential frontiers of FMT.<br><br>METHODS: Articles relating to FMT that were published between the years 2012 and 2021 were retrieved from the Web of Science Core Collection. Bibliometric analysis was performed using Microsoft Excel and CiteSpace.<br><br>RESULTS: A total of 2,403 English language articles relating to FMT research were published over the last ten years. Most of this research was carried out in the United States of America, with Harvard Medical school being the most productive institution. Much of the research was published in the PLoS One journal. Alexander Khoruts was identified as a prominent, productive researcher in the field. Keyword analysis revealed that research hot spots included gut microbiota, Clostridium difficile infection (CDI), and diseases. Burst detection indicated that future research frontiers include clinical practice guidelines and strategies.<br><br>CONCLUSION: Our analysis explored hot spots and emerging trends in the FMT field. Indications for use of FMT extended from digestive system diseases to other systemic diseases. Additionally, areas such as risk assessment and control, along with application methods were also a focus of current research. Moreover, research relating to optimization of clinical practice has excellent prospects.}, }
@article {pmid36439219, year = {2022}, author = {Wang, J and Chen, J and Chen, M}, title = {Commentary: Effect of fecal microbiota transplantation on non-alcoholic fatty liver disease: A randomized clinical trial.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1056394}, pmid = {36439219}, issn = {2235-2988}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Non-alcoholic Fatty Liver Disease/therapy ; }, }
@article {pmid36438048, year = {2022}, author = {Orr, MR}, title = {The biodiversity dose-response curve translates theory and practice from ecological restoration into research and clinical priorities for fecal microbiota transplantation.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1059148}, pmid = {36438048}, issn = {2296-858X}, abstract = {Discoveries of the beneficial effects of gut microbiota have led to efforts to cultivate healthy gut flora to treat disease. The field of ecological restoration specializes on reestablishment of desired species in disturbed ecosystems, which suggests that it may be applicable to microbe restoration in the gut. Common language can lower barriers to interdisciplinary insights. Here I introduce the concept of a "biodiversity dose-response curve" to translate ideas from ecological restoration into research and clinical priorities for fecal microbiota transplantation (FMT). The curve is based on a relationship between ecosystem structure, measured as species diversity found in both nature and gut ecosystems, and ecosystem function, which are the measurable parameters that contribute to ecosystem and human health. I explain why the biodiversity dose-response curve may follow the ecological model of a "rivet-redundancy" relationship, in which the overlap of multiple organisms' functional contributions to a system mask the impact of initial losses of diversity, but, at a certain level of loss, function declines sharply. (Imagine an airplane that flies with a few rivets missing, until it loses enough to fail.) The biodiversity dose-response curve indicates that seemingly healthy individuals may be suboptimal donors; it highlights the importance of recipient diet in FMT success; and it introduces the concept of "passive restoration" into the field of gut medicine. These insights, which may help to explain low success rates of FMT in the treatment of non-Clostridium dificile conditions, are less apparent in the absence of interdisciplinary integration.}, }
@article {pmid36432617, year = {2022}, author = {Tang, W and Yuan, M and Li, Z and Lin, Q and Zhen, Y and Li, Z and Zhou, H and Xia, F}, title = {Polyphenol-Rich Liupao Tea Extract Prevents High-Fat Diet-Induced MAFLD by Modulating the Gut Microbiota.}, journal = {Nutrients}, volume = {14}, number = {22}, pages = {}, pmid = {36432617}, issn = {2072-6643}, support = {No. 82104625//National Natural Science Foundation of China/ ; No. 82102501//National Natural Science Foundation of China/ ; No.82130068//National Natural Science Foundation of China/ ; No. 81925026//National Natural Science Foundation of China/ ; Project No. F121ZJ0236//China Postdoctoral Science Foundation Funded Project/ ; }, mesh = {Male ; Mice ; Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Polyphenols/pharmacology ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; *Liver Diseases ; *Metabolic Diseases ; *Digestive System Diseases ; Tea ; }, abstract = {The modulation of gut microbiota dysbiosis might regulate the progression of metabolic-associated fatty liver disease (MAFLD). Here, we found that polyphenol-rich Liupao tea extract (PLE) prevents high-fat diet (HFD)-induced MAFLD in ApoE[-/-] male mice accompanied by protection of the intestinal barrier and downregulation of lipopolysaccharide (LPS)-related Toll-like receptor 4 (TLR4)-myeloid differentiation primary response 88 (MyD88) signaling in the liver. Fecal microbiome transplantation (FMT) from PLE-and-HFD-treated mice delayed MAFLD development significantly compared with FMT from HFD-treated mice. In this case, 16S rRNA gene sequencing revealed that Rikenellaceae and Odoribacter were significantly enriched and that Helicobacter was significantly decreased in not only the HFD+PLE group but also the HFD+PLE-FMT group. Furthermore, the level of 3-sulfodeoxycholic acid was significantly decreased in the HFD+PLE-FMT group compared with the HFD-FMT group. In conclusion, our data demonstrate that PLE could modulate the MAFLD phenotype in mice and that this effect is partly mediated through modulation of the gut microbiota.}, }
@article {pmid36431177, year = {2022}, author = {Zhi, W and Yuan, X and Song, W and Jin, G and Li, Y}, title = {Fecal Microbiota Transplantation May Represent a Good Approach for Patients with Focal Segmental Glomerulosclerosis: A Brief Report.}, journal = {Journal of clinical medicine}, volume = {11}, number = {22}, pages = {}, pmid = {36431177}, issn = {2077-0383}, support = {82170716//National Natural Science Foundation of China, Gut microbiota promotes IgAN through CASP-1/IL-1&#x3b2;-driven increased intestinal permeability/ ; }, abstract = {This is the first report of fecal microbiota transplantation (FMT) in patients with chronic kidney disease. The patient was subjected to focal segmental glomerulosclerosis (FSGS), with onset in April 2021. The main manifestation featured abnormal renal function and no proteinuria at the level of nephrotic syndrome. In May 2021, she showed biopsy-proven FSGS and was treated with glucocorticoid. However, after glucocorticoid reduction, the patient's serum creatinine increased again, so she adjusted the dosage and continued use until now. In April 2022, the patient was prescribed the FMT capsules. After FMT, the renal function remained stable, urinary protein decreased, reaching the clinical standard of complete remission, and there was no recurrence after glucocorticoid reduction. Furthermore, the patient showed significantly decreased hyperlipidemia, triglyceride (TG) and cholesterol (CHO) after FMT. During FMT, the level of cytokines fluctuated slightly, but returned to the pre-transplantation level after three months. From this, we conclude that FMT is a potential adjuvant therapy for FSGS, and patients can benefit from improving renal function and dyslipidemia.}, }
@article {pmid36429112, year = {2022}, author = {Qi, X and Liu, Y and Hussein, S and Choi, G and Kimchi, ET and Staveley-O'Carroll, KF and Li, G}, title = {The Species of Gut Bacteria Associated with Antitumor Immunity in Cancer Therapy.}, journal = {Cells}, volume = {11}, number = {22}, pages = {}, pmid = {36429112}, issn = {2073-4409}, support = {R01 CA208396/CA/NCI NIH HHS/United States ; R01 CA208396/NH/NIH HHS/United States ; R01 CA250536/NH/NIH HHS/United States ; R01 CA250536/CA/NCI NIH HHS/United States ; R01 DK130340/NH/NIH HHS/United States ; R01 DK130340/DK/NIDDK NIH HHS/United States ; I01 BX004065/BX/BLRD VA/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Bacteria ; *Probiotics/therapeutic use ; *Neoplasms/therapy ; }, abstract = {Both preclinical and clinical studies have demonstrated that the modulation of gut microbiota could be a promising strategy for enhancing antitumor immune responses and reducing resistance to immunotherapy in cancer. Various mechanisms, including activation of pattern recognition receptors, gut commensals-produced metabolites and antigen mimicry, have been revealed. Different gut microbiota modulation strategies have been raised, such as fecal microbiota transplantation, probiotics, and dietary selection. However, the identification of gut bacteria species that are either favorable or unfavorable for cancer therapy remains a major challenge. Herein, we summarized the findings related to gut microbiota species observed in the modulation of antitumor immunity. We also discussed the different mechanisms underlying different gut bacteria's functions and the potential applications of these bacteria to cancer immunotherapy in the future.}, }
@article {pmid36425787, year = {2022}, author = {Fang, J and Yu, CH and Li, XJ and Yao, JM and Fang, ZY and Yoon, SH and Yu, WY}, title = {Gut dysbiosis in nonalcoholic fatty liver disease: pathogenesis, diagnosis, and therapeutic implications.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {997018}, pmid = {36425787}, issn = {2235-2988}, mesh = {Humans ; Dysbiosis/therapy/microbiology ; *Non-alcoholic Fatty Liver Disease/diagnosis/therapy/metabolism ; *Gastrointestinal Microbiome ; *Liver Neoplasms ; }, abstract = {The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing recently and has become one of the most common clinical liver diseases. Since the pathogenesis of NAFLD has not been completely elucidated, few effective therapeutic drugs are available. As the "second genome" of human body, gut microbiota plays an important role in the digestion, absorption and metabolism of food and drugs. Gut microbiota can act as an important driver to advance the occurrence and development of NAFLD, and to accelerate its progression to cirrhosis and hepatocellular carcinoma. Growing evidence has demonstrated that gut microbiota and its metabolites directly affect intestinal morphology and immune response, resulting in the abnormal activation of inflammation and intestinal endotoxemia; gut dysbiosis also causes dysfunction of gut-liver axis via alteration of bile acid metabolism pathway. Because of its composition diversity and disease-specific expression characteristics, gut microbiota holds strong promise as novel biomarkers and therapeutic targets for NAFLD. Intervening intestinal microbiota, such as antibiotic/probiotic treatment and fecal transplantation, has been a novel strategy for preventing and treating NAFLD. In this article, we have reviewed the emerging functions and association of gut bacterial components in different stages of NAFLD progression and discussed its potential implications in NAFLD diagnosis and therapy.}, }
@article {pmid36425405, year = {2022}, author = {Seekatz, AM and Safdar, N and Khanna, S}, title = {The role of the gut microbiome in colonization resistance and recurrent Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {15}, number = {}, pages = {17562848221134396}, pmid = {36425405}, issn = {1756-283X}, support = {K01 DK111794/DK/NIDDK NIH HHS/United States ; }, abstract = {UNLABELLED: The species composition of the human gut microbiota is related to overall health, and a healthy gut microbiome is crucial in maintaining colonization resistance against pathogens. Disruption of gut microbiome composition and functionality reduces colonization resistance and has been associated with several gastrointestinal and non-gastrointestinal diseases. One prime example is Clostridioides difficile infection (CDI) and subsequent recurrent infections that occur after the development of systemic antibiotic-related dysbiosis. Standard-of-care antibiotics used for both acute and recurrent infections do not address dysbiosis and often worsen the condition. Moreover, monoclonal antibodies, recommended in conjunction with standard-of-care antibiotics for the prevention of recurrent CDI in patients at high risk of recurrence, reduce recurrences but do not address the underlying dysbiosis. Fecal microbiota transplantation (FMT) is an evolving therapeutic strategy in which microbes are harvested from healthy donor stool and transplanted into the gut of a recipient to restore the gut microbiome. Although effective in the prevention of recurrent CDI, some existing challenges include screening and the standardization of stool acquisition and processing. Recent safety alerts by the US Food and Drug Administration raised concern about the possibility of transmission of multidrug-resistant organisms or severe acute respiratory syndrome coronavirus 2 via FMT. Increased knowledge that microbes are beneficial in restoring the gut microbiome has led to the clinical development of several newer biotherapeutic formulations that are more regulated than FMT, which may allow for improved restoration of the gut microbiome and prevention of CDI recurrence. This review focuses on mechanisms by which gut microbiome restoration could influence colonization resistance against the pathogen C. difficile.<br><br>PLAIN LANGUAGE SUMMARY: The Role of the Gut Microbiome in Clostridioides difficile Infection Introduction: A rich and diverse gut microbiome is key to immune system regulation and colonization resistance against pathogens.A disruption in the gut microbiome composition can make the gut more vulnerable to diseases such as Clostridioides difficile infection (CDI), caused by the bacterium C. difficile.CDI management presents a therapeutic dilemma, as it is usually treated with antibiotics that can treat the infection but also can damage the microbiome.Treatment of CDI using antibiotics can further reduce microbial diversity and deplete beneficial bacteria from the gut leading to a condition called dysbiosis.Antibiotic treatment can be followed by therapies that restore the gut microbiota, boost colonization resistance, and prevent the development of antimicrobial resistance.It is important to evaluate treatment options to determine their safety and effectiveness. Methods: The researchers provided an overview of the mechanisms that the gut microbiome uses to prevent colonization of the gut by pathogens.They subsequently reviewed the efficacy and shortcomings of the following treatments for CDI: -&#x2003;Antibiotics-&#x2003;Monoclonal antibodies-&#x2003;Fecal microbiota transplantation (FMT) Results: Commensal intestinal bacteria prevent colonization of the gut by pathogens using mechanisms such as: -&#x2003;Competition for key nutrients-&#x2003;Production of inhibitory bile acids-&#x2003;Short-chain fatty acid production-&#x2003;Lowering the luminal pH-&#x2003;Production of bacteriocinsAntibiotic therapy is recommended as a standard treatment for CDI. However, patients are vulnerable to recurrent CDI after discontinuation of the therapy.Monoclonal antibodies that inactivate C. difficile toxins may be recommended along with antibiotics to prevent recurrent CDI. However, this approach does not restore the microbiome.FMT is one method of microbial restoration, where stool is harvested from a healthy donor and transplanted into a patient's colon.Although FMT has shown some efficacy in the treatment of recurrent CDI, the procedure is not standardized.Safety concerns have been raised about the possibility of transmission of multidrug-resistant pathogens via FMT. Conclusion: Treatment methods that can efficiently restore the diversity of the gut microbiome are crucial in preventing recurrence of CDI.}, }
@article {pmid36424781, year = {2023}, author = {Rastogi, S and Singh, A and Nandi, A and Gupta, A and Agarwal, J and Kostova, I}, title = {Can the Therapeutic Spectrum of Probiotics be Extended: Exploring Potential of Gut Microbiome.}, journal = {Recent advances in anti-infective drug discovery}, volume = {18}, number = {2}, pages = {120-147}, doi = {10.2174/2772434418666221124124317}, pmid = {36424781}, issn = {2772-4352}, support = {//Amity University/ ; }, mesh = {Female ; Humans ; *Gastrointestinal Microbiome ; *COVID-19 ; Lactobacillus ; *Autoimmune Diseases ; *Probiotics/therapeutic use ; }, abstract = {Natural therapeutic microorganisms provide a potent alternative healthcare treatment nowadays, with the potential to prevent several human diseases. These health-boosting living organisms, probiotics mostly belong to Gram-positive bacteria such as Lactobacillus, Bifidobacterium, Streptococcus, Saccharomyces, Bacillus and Enterococcus. Initiated almost a century ago, the probiotic application has come a long way. The present review is focused on the potential therapeutic role of probiotics in ameliorating multiple infections, such as upper respiratory tract infections and viral respiratory infections, including COVID-19; liver diseases and hepatic encephalopathy; neurological and psychiatric disorders; autoimmune diseases, particularly rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. Apart from these, the therapeutic exacerbations of probiotics in urinary tract infections have been extremely promising, and several approaches are reviewed and presented here. We also present upcoming and new thrust areas where probiotic therapeutic interventions are showing promising results, like faecal microbial transplant and vaginal microbial transplant.}, }
@article {pmid36424592, year = {2022}, author = {Gu, X and Miao, Z and Wang, Y and Yang, Y and Yang, T and Xu, Y}, title = {New Baitouweng decoction combined with fecal microbiota transplantation alleviates DSS-induced colitis in rats by regulating gut microbiota metabolic homeostasis and the STAT3/NF-κB signaling pathway.}, journal = {BMC complementary medicine and therapies}, volume = {22}, number = {1}, pages = {307}, pmid = {36424592}, issn = {2662-7671}, mesh = {Rats ; Animals ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; NF-kappa B/metabolism ; Dextran Sulfate/pharmacology ; *Colitis ; *Colitis, Ulcerative/therapy/metabolism ; Signal Transduction ; Homeostasis ; }, abstract = {AIM OF THE STUDY: We aimed to elucidate the synergistic effect and potential mechanism of New Baitouweng Decoction (NBD) combined with fecal microbiota transplantation (FMT) in rats with DSS-induced ulcerative colitis (UC).<br><br>MATERIALS AND METHODS: Colitis was induced by 5% (w/v) dextran sulfate sodium (DSS) in drinking water for 7&#x2009;days. NBD or NBD combined with FMT were administered to the colitis rats. Body weight and disease activity index were measured, and the colon histological change was imaged to further examine the efficacy of NBD and FMT. The specific effects of NBD on STAT3/NF-&#x3ba;B signaling pathway and gut microbiota in rats with UC were also investigated.<br><br>RESULTS: The efficacy of NBD in combination with FMT was demonstrated by the lower disease activity index scores; increased tight junction proteins expression; and a lower expression of macrophage marker (F4/80) in colon tissues. NBD combined with FMT elevated the concentrations of short-chain fatty acids and inhibited activation of the JAK2/STAT3/NF-&#x3ba;B related proteins. Furthermore, 16SrDNA sequencing indicated that the gut microbiota in rats with UC was perturbed, in contrast to that in healthy rats. After treatment with NBD and FMT, the diversity and abundance of intestinal flora showed clear improvements. Spearman correlation analysis indicated a strong correlation between specific microbiota and fecal concentrations of acetate, propionate and butyrate.<br><br>CONCLUSIONS: The protective mechanism of NBD combined with FMT may be linked to regulation NF-&#x3ba;B/STAT3 and restoration of the intestinal flora.}, }
@article {pmid36422528, year = {2022}, author = {Franc, A and Vetchý, D and Fülöpová, N}, title = {Commercially Available Enteric Empty Hard Capsules, Production Technology and Application.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {15}, number = {11}, pages = {}, pmid = {36422528}, issn = {1424-8247}, support = {MUNI/IGA/0942/2021//Masaryk University/ ; }, abstract = {Currently, there is a growing need to prepare small batches of enteric capsules for individual therapy or clinical evaluation since many acidic-sensitive substances should be protected from the stomach's acidic environment, including probiotics or fecal material, in the fecal microbiota transplantation (FMT) process. A suitable method seems to be the encapsulation of drugs or lyophilized alternatively frozen biological suspensions in commercial hard enteric capsules prepared by so-called Enteric Capsule Drug Delivery Technology (ECDDT). Manufacturers supply these types of capsules, made from pH-soluble polymers, in products such as AR Caps[®], EnTRinsic[TM], and Vcaps[®] Enteric, or capsules made of gelling polymers that release their content as the gel erodes over time when passing through the digestive tract. These include DRcaps[®], EMBO CAPS[®] AP, BioVXR[®], or ACGcaps™ HD. Although not all capsules in all formulations meet pharmaceutical requirements for delayed-release dosage forms in disintegration and dissolution tests, they usually find practical application. This literature review presents their composition and properties. Since ECDDT is a new technology, this article is based on a limited number of references.}, }
@article {pmid36422003, year = {2022}, author = {Zhuang, Y and Zeng, R and Liu, X and Yang, L and Chan, Z}, title = {Neoagaro-Oligosaccharides Ameliorate Chronic Restraint Stress-Induced Depression by Increasing 5-HT and BDNF in the Brain and Remodeling the Gut Microbiota of Mice.}, journal = {Marine drugs}, volume = {20}, number = {11}, pages = {}, pmid = {36422003}, issn = {1660-3397}, support = {no. 2022H0036//Fujian Provincial Science and Technology Project/ ; }, mesh = {Animals ; Mice ; *Brain-Derived Neurotrophic Factor/metabolism ; Depression/drug therapy/etiology ; *Gastrointestinal Microbiome ; Serotonin ; Interleukin-18 ; Mice, Inbred C57BL ; Brain/metabolism ; Oligosaccharides/pharmacology/therapeutic use ; Disease Models, Animal ; }, abstract = {Neoagaro-oligosaccharides (NAOs) belong to the algae oligosaccharides. NAOs have been found to have diverse biological activities. However, the effects of NAOs on depression and their underlying mechanism have not been thoroughly studied. A chronic restraint stress (CRS)-induced C57BL/6J mouse model was used to assess the antidepressant effects of NAOs. Anxiety and depression behaviors were assessed by open field tests (OFT) and forced swimming tests (FST), while interleukin 18 (IL-18), 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) were the molecular biomarkers of depression. Fecal microbiota transplantation (FMT) was performed. The results showed that NAO treatment significantly improved the body weight of depressed mice and reduced the central area time in the OFT and immobility time in the FST. NAO treatment decreased the levels of IL-18 in the serum and increased the levels of 5-HT in the serum and whole brain and of BDNF in the whole brain. NAO treatment mitigated the gut microbiota dysbiosis in the depressed mice and reversed the decreased levels of short-chain fatty acids (SCFAs) in the cecum of the depressed mice. FMT indicated that the gut microbiota is, indeed, linked to depression, which was reflected in the changes in weight gain and behaviors. In a word, NAOs effectively reversed the CRS-induced mice model of depression, which depended on the changes in the gut microbiota and SCFAs, as well as its modulation of 5-HT and BDNF.}, }
@article {pmid36420886, year = {2023}, author = {Zhang, LN and Yuan, WL and Ye, M and Yin, L and Wang, SJ}, title = {Changes in the intestinal microbiota of patients with Parkinson's disease and their clinical significance.}, journal = {International journal of clinical pharmacology and therapeutics}, volume = {61}, number = {2}, pages = {48-58}, doi = {10.5414/CP204285}, pmid = {36420886}, issn = {0946-1965}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Parkinson Disease/diagnosis ; Clinical Relevance ; Feces/microbiology ; Biomarkers ; }, abstract = {OBJECTIVE: To investigate the differences and their clinical significance in the intestinal microbiota in patients with Parkinson's disease (PD) in comparison to those in healthy controls.<br><br>MATERIALS AND METHODS: 20 patients with PD who received treatment in the First Affiliated Hospital of Bengbu Medical College between January 2019 and December 2019 were selected as the research subjects to form the PD group, while 20 age- and gender-matched healthy volunteers were selected as the control group. Fecal samples from the two groups were collected, and the V4 region of 16S-ribosomal ribonucleic acid was selected for high-throughput sequencing analysis to explore any differences, as well as their significance, in the intestinal microbiota abundance at the class, family, and genus levels between the two study groups.<br><br>RESULTS: The operational taxonomic unit cluster analysis revealed a high degree of overlap between the patients with PD and the controls. Compared with the controls, the relative abundance of Coriobacteriia and Coriobacteriaceae was increased in the PD group (p&#xa0;<&#xa0;0.01), while the relative abundance of Lachnospiraceae was significantly lower (p&#xa0;<&#xa0;0.01). The relative abundance of Collinsella, Escherichia, and Fusobacterium in the PD group was significantly higher than in the control group (p&#xa0;<&#xa0;0.05).<br><br>CONCLUSION: Compared with the healthy subjects, the abundance of specific microflora was significantly different in the PD patients at the class, family, and genus level. Intestinal flora may act as a potential biomarker for PD and provide a theoretical basis for microflora transplantation therapy.}, }
@article {pmid36420262, year = {2022}, author = {Wang, X and Li, L and Bai, M and Zhao, J and Sun, X and Gao, Y and Yu, H and Chen, X and Zhang, C}, title = {Dietary supplementation with Tolypocladium sinense mycelium prevents dyslipidemia inflammation in high fat diet mice by modulation of gut microbiota in mice.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {977528}, pmid = {36420262}, issn = {1664-3224}, mesh = {Mycelium ; Dietary Supplements ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome ; *Metabolic Diseases ; Obesity/prevention &amp; control ; Mice ; Animals ; *Dyslipidemias/etiology/prevention &amp; control ; Inflammation/prevention &amp; control ; Hypocreales ; Diet, High-Fat/adverse effects ; Humans ; }, abstract = {Obesity is a risk factor for many serious health problems, associated with inflammation, hyperlipidemia, and gut dysbiosis. Prevention of obesity is especially important for human health. Tolypocladium sinense is one of the fungi isolated from Chinese caterpillar fungus, which is a traditional Chinese medicine with putative gut microbiota modulation effects. Here, we established a high-fat diet (HFD)-induced hyperlipidemia mice model, which was supplemented with lyophilized T. sinense mycelium (TSP) daily to evaluate its anti-obesity effects. The results indicated that TSP supplementation can effectively alleviate the inflammatory response and oxidative stress levels caused by obesity. TSP significantly prevented obesity and suppressed dyslipidemia by regulating the expression of lipid metabolism genes in the liver. TSP is also effective in preventing the HFD-induced decline in short-chain fatty acid (SCFA) content. Gut microbiota profiling showed that TSP supplementation reversed HFD diet-induced bacterial abundance and also altered the metabolic pathways of functional microorganisms, as revealed by KEGG analysis. It is noteworthy that, correlation analysis reveals the up-regulated gut microbiota (Lactobacillus and Prevotella_9) are closely correlated with lipid metabolism parameters, gene expression of liver lipid metabolism and inflammatory. Additionally, the role of TSP in the regulation of lipid metabolism was reconfirmed by fecal microbiota transplantation. To sum up, our results provide the evidence that TSP may be used as prebiotic agents to prevent obesity by altering the gut microbiota, alleviating the inflammatory response and regulating gene expression of liver lipid metabolism.}, }
@article {pmid36418892, year = {2023}, author = {Zou, MY and Wang, YJ and Liu, Y and Xiong, SQ and Zhang, L and Wang, JH}, title = {Huangshan Floral Mushroom Polysaccharide Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Th17/Treg Balance in a Gut Microbiota-Dependent Manner.}, journal = {Molecular nutrition &amp; food research}, volume = {67}, number = {2}, pages = {e2200408}, doi = {10.1002/mnfr.202200408}, pmid = {36418892}, issn = {1613-4133}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Dextran Sulfate/toxicity ; Colon/metabolism ; T-Lymphocytes, Regulatory/metabolism ; *Agaricales ; *Colitis/chemically induced/metabolism ; *Colitis, Ulcerative/chemically induced/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Th17 Cells/metabolism ; }, abstract = {SCOPE: Ulcerative colitis (UC) is a common chronic recurrent inflammatory bowel disease. This study attempts to reveal the improvement mechanism of floral mushroom polysaccharide (FMPS) on UC from the perspective of coordinated interaction between intestinal microbes and intestinal helper T cell 17 (Th17)/regulatory T cell (Treg) balance.<br><br>METHODS AND RESULTS: Dextran sulfate sodium (DSS)-induced colitis mice model is used for the experiment. The results suggest that FMPS up-regulated the expression of occludin, ZO-1, and MUC2, and down-regulated the secretion of TNF-&#x3b1;, IL-1&#x3b2;, and IL-6 in colitis mice. Importantly, FMPS restores intestinal Th17/Treg balance. Meanwhile, FMPS can regulate intestinal microorganisms and improve the level of short-chain fatty acids (SCFAs) in colitis mice. Intestinal microbial depletion and fecal microbiota transplantation (FMT) experiments reveal that FMPS ameliorated UC is mediated by intestinal microbiome. Flow cytometry further proves that FMPS restores intestinal Th17/Treg balance in a microbial-dependent manner.<br><br>CONCLUSION: These results indicate that FMPS has the potential to improve UC, and its mechanism depends on the restoration of Th17/Treg balance mediated by intestinal microorganisms. Therefore, it is suggested that FMPS dietary supplement can be potentially used to intervene UC.}, }
@article {pmid36417859, year = {2022}, author = {Zhao, C and Bao, L and Qiu, M and Wu, K and Zhao, Y and Feng, L and Xiang, K and Zhang, N and Hu, X and Fu, Y}, title = {Commensal cow Roseburia reduces gut-dysbiosis-induced mastitis through inhibiting bacterial translocation by producing butyrate in mice.}, journal = {Cell reports}, volume = {41}, number = {8}, pages = {111681}, doi = {10.1016/j.celrep.2022.111681}, pmid = {36417859}, issn = {2211-1247}, mesh = {Female ; Cattle ; Mice ; Animals ; Humans ; Dysbiosis/complications ; Bacterial Translocation ; Butyrates/pharmacology ; *Gastrointestinal Microbiome/physiology ; *Mastitis/complications ; }, abstract = {The precise mechanism by which gut dysbiosis contributes to the pathogenesis of extraintestinal diseases and how commensal microbes mediate these processes remain unclear. Here, we show that cows with mastitis had marked gut dysbiosis, characterized by the enrichment of opportunistic pathogenic Escherichia_Shigella and the depletion of commensal Roseburia. Fecal microbiota transplantation from donor cows with mastitis (M-FMT) to recipient mice significantly caused mastitis and changed the gut and mammary microbiota in mice. Notably, M-FMT facilitated the translocation of pathobiont from the gut into the mammary gland, and the depletion of Enterobacteriaceae alleviated M-FMT-induced mastitis in mice. In contrast, commensal Roseburia intestinalis improved M-FMT-induced mastitis and microbial dysbiosis in the gut and mammary gland and limited bacterial translocation by producing butyrate, which was associated with inflammatory signaling inhibition and barrier repair. Our research suggests that commensal Roseburia alleviates gut-dysbiosis-induced mastitis, although further studies in dairy cows and humans are needed.}, }
@article {pmid36414201, year = {2023}, author = {Liu, Q and Xu, Z and Dai, M and Su, Q and Leung Chan, FK and Ng, SC}, title = {Faecal microbiota transplantations and the role of bacteriophages.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {29}, number = {6}, pages = {689-694}, doi = {10.1016/j.cmi.2022.11.012}, pmid = {36414201}, issn = {1469-0691}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Bacteriophages ; *Clostridium Infections/therapy/microbiology ; *Microbiota ; *Gastrointestinal Microbiome ; Feces/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Bacteriophages are a major component of the human gut microbiota. Emerging evidence suggests that gut bacteriophages play an important role in the intricate dynamics with bacteria, and their transfer may be associated with the efficacy of faecal microbiota transplantation (FMT).<br><br>OBJECTIVES: To summarize our current knowledge of the changes in gut bacteriophage communities during FMT and their association with FMT outcome.<br><br>SOURCES: PubMed, Web of Science, and Google Scholar were searched for articles on FMT and bacteriophages published between May 2013 and January 2022.<br><br>CONTENT: Preclinical and clinical studies have reported associations between gut bacteriophage profiles and FMT. FMT was associated with donor-specific engraftment of bacteriophages, characterized by increased viral diversity and richness, and the bacteriophage composition resembled the donor's profile after FMT. Limited studies showed that cure after FMT was more likely when an increased fraction of the recipient enteric virome was occupied by donor-derived taxa, including Caudovirales in Clostridioides difficile infection. Faecal virome transplant involving the transfer of the gut virome communities alone may also induce phenotypical and microbiome improvement in various diseases.<br><br>IMPLICATIONS: The accumulating evidence that bacteriophages play roles in FMT efficacy has attracted considerable interest. Better characterization of bacteriophages and an understanding of their underlying mechanisms in FMT are warranted.}, }
@article {pmid36414164, year = {2023}, author = {Lee, EH and Lee, SK and Cheon, JH and Koh, H and Lee, JA and Kim, CH and Kim, JN and Lee, KH and Lee, SJ and Kim, JH and Ahn, JY and Jeong, SJ and Ku, NS and Yong, DE and Yoon, SS and Yeom, JS and Choi, JY}, title = {Comparing the efficacy of different methods of faecal microbiota transplantation via oral capsule, oesophagogastroduodenoscopy, colonoscopy, or gastric tube.}, journal = {The Journal of hospital infection}, volume = {131}, number = {}, pages = {234-243}, doi = {10.1016/j.jhin.2022.11.007}, pmid = {36414164}, issn = {1532-2939}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Feces ; Prospective Studies ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Colonoscopy ; Endoscopy, Digestive System ; Treatment Outcome ; }, abstract = {BACKGROUND: The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been discussed as a novel and effective method for decolonizing MDRO.<br><br>AIM: To compare the efficacy of different FMT methods to optimize the success rate of decolonization in patients with MDRO carriage.<br><br>METHODS: This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube.<br><br>FINDINGS: A total of 57 patients underwent FMT for MDRO decolonization. The colonoscopy group required the shortest time for decolonization, whereas the EGD group required the longest (24.9 vs 190.4 days, P&#xa0;= 0.022). The decolonization rate in the oral capsule group was comparable to that in the EGD group (84.6% vs 85.7%, P&#xa0;= 0.730). An important clinical factor associated with decolonization failure was antibiotic use after FMT (odds ratio&#xa0;= 6.810, P&#xa0;= 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT.<br><br>CONCLUSION: Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonization.}, }
@article {pmid36412458, year = {2023}, author = {Mahmoudi, H and Hossainpour, H}, title = {Application and development of fecal microbiota transplantation in the treatment of gastrointestinal and metabolic diseases: A review.}, journal = {Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association}, volume = {29}, number = {1}, pages = {3-11}, pmid = {36412458}, issn = {1998-4049}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Irritable Bowel Syndrome/therapy ; *Clostridioides difficile ; *COVID-19 ; SARS-CoV-2 ; Feces ; *Gastrointestinal Diseases/therapy ; *Inflammatory Bowel Diseases/therapy ; *Clostridium Infections ; *Metabolic Diseases ; Treatment Outcome ; Recurrence ; }, abstract = {Fecal microbiota transplantation (FMT) restores a balanced intestinal flora, which helps to cure recurrent Clostridium difficile infections (RCDI). FMT has also been used to treat other gastrointestinal diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and chronic constipation, as well as a variety of non-GI disorders. The purpose of this review is to discuss gut microbiota and FMT treatment of GI and non-GI diseases. An imbalanced gut microbiota is known to predispose one to Clostridium difficile infections (CDI), IBD, and IBS. However, the complex role of the gut microbiota in maintaining health is a newer concept that is being increasingly studied. The microbiome plays a major role in cellular immunity and metabolism and has been implicated in the pathogenesis of non-GI autoimmune diseases, chronic fatigue syndrome, obesity, and even some neuropsychiatric disorders. Many recent studies have reported that viral gastroenteritis can affect intestinal epithelial cells, and SARS-CoV-2 virus has been identified in the stool of infected patients. FMT is a highly effective cure for RCDI, but a better understanding of the gut microbiota in maintaining health and controlled studies of FMT in a variety of conditions are needed before FMT can be accepted and used clinically.}, }
@article {pmid36409919, year = {2022}, author = {Chen, X and Hashimoto, D and Ebata, K and Takahashi, S and Shimizu, Y and Shinozaki, R and Hasegawa, Y and Kikuchi, R and Senjo, H and Yoneda, K and Zhang, Z and Harada, S and Hayase, E and Ara, T and Ohigashi, H and Iwakura, Y and Nakamura, K and Ayabe, T and Teshima, T}, title = {Reactive granulopoiesis depends on T-cell production of IL-17A and neutropenia-associated alteration of gut microbiota.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {48}, pages = {e2211230119}, pmid = {36409919}, issn = {1091-6490}, mesh = {Mice ; Animals ; Interleukin-17 ; T-Lymphocytes ; *Gastrointestinal Microbiome ; Mice, Knockout ; *Neutropenia ; }, abstract = {Granulopoiesis in the bone marrow adjusts cellular output as demand for neutrophils changes. Reactive granulopoiesis is induced by profound neutropenia, but its mechanism remains to be clarified. We herein explored its mechanisms using mouse models of syngeneic hematopoietic stem cell transplantation (SCT) and 5-fluorouracil-induced neutropenia. After SCT, T cell production of IL-17A was up-regulated. Neutrophil recovery was significantly delayed in IL-17A-deficient or T cell-deficient RAG1[-/-] mice, and adoptive transfer of wild-type (WT) T cells facilitated neutrophil engraftment. Gut decontamination with oral antibiotics suppressed T cell production of IL-17A and impaired neutrophil recovery. Transplantation of fecal microbiota collected from neutropenic, not naive, mice promoted neutrophil recovery in these mice, suggesting that neutropenia-associated microbiota had a potential to stimulate reactive granulopoiesis. Our study uncovered a cross talk between gut microbiota and neutropenia after SCT and chemotherapy.}, }
@article {pmid36408726, year = {2023}, author = {Wang, L and Shao, L and Chen, MY and Wang, L and Yang, P and Tan, FB and Zhang, W and Huang, WH}, title = {Panax notoginseng Alleviates Colitis via the Regulation of Gut Microbiota.}, journal = {The American journal of Chinese medicine}, volume = {51}, number = {1}, pages = {107-127}, doi = {10.1142/S0192415X23500076}, pmid = {36408726}, issn = {1793-6853}, mesh = {Animals ; Mice ; *Panax notoginseng ; *Gastrointestinal Microbiome ; *Colitis/chemically induced/drug therapy ; *Saponins/pharmacology ; *Inflammatory Bowel Diseases ; Interleukin-1/metabolism ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; Mice, Inbred C57BL ; Colon/metabolism ; }, abstract = {Gut microbiota are significantly associated with the occurrence and development of inflammatory bowel disease (IBD). Panax notoginseng saponins (PNS) could be used for colitis and to modulate gut microbiota. However, the mechanism behind the effects of PNS on anti-colitis that are pertinent to gut microbiota is largely unknown. This study aimed to evaluate the anti-colitis effects of PNS and explore the involved mechanism as it is related to gut microbiota. Results showed that PNS significantly alleviated dextran sulfate sodium (DSS)-induced colitis. Meanwhile, after PNS treatment, the tight junction proteins were enhanced and proinflammatory cytokines, such as TNF-[Formula: see text], IL-6, IL-1[Formula: see text], and IL-17, were decreased. Furthermore, Bacteroides spp. were significantly increased after modeling, while PNS reduced their abundance and significantly increased the amount of Akkermansia spp. in vivo. Importantly, Akkermansia spp. and Bacteroides spp. were correlated with the IBD disease indicators. Moreover, fecal microbiota transplantation (FMT) experiments confirmed that PNS-reshaped gut microbiota significantly alleviated DSS-induced colitis, while A. muciniphila significantly reduced the levels of the LPS-induced cellular inflammatory factors IL-1[Formula: see text] and TNF-[Formula: see text]. In conclusion, PNS alleviated colitis pertinent to the upregulation of Akkermania spp. and downregulation of Bacteroides spp. in the gut.}, }
@article {pmid36407764, year = {2022}, author = {Melamed, E and Palmer, JL and Fonken, C}, title = {Advantages and limitations of experimental autoimmune encephalomyelitis in breaking down the role of the gut microbiome in multiple sclerosis.}, journal = {Frontiers in molecular neuroscience}, volume = {15}, number = {}, pages = {1019877}, pmid = {36407764}, issn = {1662-5099}, support = {K08 AA027837/AA/NIAAA NIH HHS/United States ; }, abstract = {Since the first model of experimental autoimmune encephalomyelitis (EAE) was introduced almost a century ago, there has been an ongoing scientific debate about the risks and benefits of using EAE as a model of multiple sclerosis (MS). While there are notable limitations of translating EAE studies directly to human patients, EAE continues to be the most widely used model of MS, and EAE studies have contributed to multiple key breakthroughs in our understanding of MS pathogenesis and discovery of MS therapeutics. In addition, insights from EAE have led to a better understanding of modifiable environmental factors that can influence MS initiation and progression. In this review, we discuss how MS patient and EAE studies compare in our learning about the role of gut microbiome, diet, alcohol, probiotics, antibiotics, and fecal microbiome transplant in neuroinflammation. Ultimately, the combination of rigorous EAE animal studies, novel bioinformatic approaches, use of human cell lines, and implementation of well-powered, age- and sex-matched randomized controlled MS patient trials will be essential for improving MS patient outcomes and developing novel MS therapeutics to prevent and revert MS disease progression.}, }
@article {pmid36406749, year = {2022}, author = {Hashim, HM and Makpol, S}, title = {A review of the preclinical and clinical studies on the role of the gut microbiome in aging and neurodegenerative diseases and its modulation.}, journal = {Frontiers in cellular neuroscience}, volume = {16}, number = {}, pages = {1007166}, pmid = {36406749}, issn = {1662-5102}, abstract = {As the world population ages, the burden of age-related health problems grows, creating a greater demand for new novel interventions for healthy aging. Advancing aging is related to a loss of beneficial mutualistic microbes in the gut microbiota caused by extrinsic and intrinsic factors such as diet, sedentary lifestyle, sleep deprivation, circadian rhythms, and oxidative stress, which emerge as essential elements in controlling and prolonging life expectancy of healthy aging. This condition is known as gut dysbiosis, and it affects normal brain function via the brain-gut microbiota (BGM) axis, which is a bidirectional link between the gastrointestinal tract (GIT) and the central nervous system (CNS) that leads to the emergence of brain disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Here, we reviewed the role of the gut microbiome in aging and neurodegenerative diseases, as well as provided a comprehensive review of recent findings from preclinical and clinical studies to present an up-to-date overview of recent advances in developing strategies to modulate the intestinal microbiome by probiotic administration, dietary intervention, fecal microbiota transplantation (FMT), and physical activity to address the aging process and prevent neurodegenerative diseases. The findings of this review will provide researchers in the fields of aging and the gut microbiome design innovative studies that leverage results from preclinical and clinical studies to better understand the nuances of aging, gut microbiome, and neurodegenerative diseases.}, }
@article {pmid36406423, year = {2022}, author = {Li, J and Lv, JL and Cao, XY and Zhang, HP and Tan, YJ and Chu, T and Zhao, LL and Liu, Z and Ren, YS}, title = {Gut microbiota dysbiosis as an inflammaging condition that regulates obesity-related retinopathy and nephropathy.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1040846}, pmid = {36406423}, issn = {1664-302X}, abstract = {Diabetes-specific microvascular disease is a leading cause of blindness, renal failure and nerve damage. Epidemiological data demonstrated that the high morbidity of T2DM occurs as a result of obesity and gradually develops into serious complications. To date, the mechanisms that underlie this observation are still ill-defined. In view of the effect of obesity on the gut microflora, Lepr[db/db] mice underwent antibiotic treatment and microbiota transplants to modify the gut microbiome to investigate whether microbes are involved in the development of diabetic nephropathy (DN) and/or diabetic retinopathy (DR). The mouse feces were collected for bacterial 16S ribosomal RNA gene sequencing. Cytokines including TNF-α, TGF-β1, IFN-γ, IL-1β, IL-6, IL-17A, IL-10, and VEGFA were detected by enzyme-linked immunosorbent assay (ELISA), flow cytometry, real-time PCR and immunofluorescent assay. Eyes and kidney were collected for histopathological assay. Intestinal permeability was also detected using Evans Blue. The results showed that obesity influenced metabolic variables (including fast/fed glucose, insulin, and triglyceride), retinopathy and nephropathy, and the gut microbiota. Obesity mainly reduced the ratio of Bacteroidetes/Firmicutes and influenced relative abundance of Proteobacteria, Actinobacteria, and Spirochetes. Obesity also increased intestinal permeability, metabolic endotoxemia, cytokines, and VEGFA. Microbiota transplants confirm that obesity aggravates retinopathy and nephropathy through the gut microbiota. These findings suggest that obesity exacerbates retinopathy and nephropathy by inducing gut microbiota dysbiosis, which further enhanced intestinal permeability and chronic low-grade inflammation.}, }
@article {pmid36405622, year = {2022}, author = {Samuthpongtorn, C and Kantagowit, P and Pittayanon, R and Patcharatrakul, T and Gonlachanvit, S}, title = {Fecal microbiota transplantation in irritable bowel syndrome: A meta-analysis of randomized controlled trials.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1039284}, pmid = {36405622}, issn = {2296-858X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) has been proposed as a potential treatment for irritable bowel syndrome (IBS); however, the consensus regarding its efficacy and safety is limited.<br><br>MATERIALS AND METHODS: We performed a systematic search of the literature using PubMed, EMBASE, Ovid MEDLINE, and Cochrane. Meta-analyses were conducted in relative risk (RR) or standard mean difference (SMD) using 95% confidence intervals (CI). Cochrane risk-of-bias 2 tool (RoB2) was employed to evaluate the study quality.<br><br>RESULT: Of 2,589 potential records, 7 studies with 9 cohorts involving 505 participants were included. Meta-analyses showed no significant difference in the short-term (12 weeks) and long-term (12 months) global improvement of IBS symptoms of FMT vs. placebo (RR 0.63, 95% CI 0.39-1.00 and RR 0.88, 95% CI 0.53-1.45, respectively). There were statistically significant differences of short-term IBS-SSS improvement (SMD -0.58, 95% CI -1.09 to -0.88) and short-term IBS-QoL improvement (SMD 0.67, 95% CI 0.43-0.91). Eight from 9 studies (88.9%) had a low risk of bias. The subgroup analysis revealed the short-term global symptoms improvement in studies with low-risk of bias (RR 0.53, 95% CI 0.35-0.81), studies with well-defined donors (RR 0.31, 95% CI 0.14-0.72), and studies with FMT using colonoscopy (RR 0.66, 95% CI 0.47-0.92). Major FMT adverse events are transient and rapidly self-limiting.<br><br>CONCLUSION: FMT significantly improved IBS-SSS and IBS-QoL in the short-term period in IBS patients. However, global symptom improvement showed no significance. Well-defined donors and appropriate fecal administration routes appear to be important factors for the successful outcomes of FMT in IBS.<br><br>[www.crd.york.ac.uk/prospero], identifier [CRD42021246101].}, }
@article {pmid36405609, year = {2022}, author = {Yadegar, A and Nabavi-Rad, A and Ochoa-Repáraz, J and Ohkusa, T and Wang, YD}, title = {Editorial: Gut microbiota and gastrointestinal disorders.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1079787}, pmid = {36405609}, issn = {2296-858X}, }
@article {pmid36399701, year = {2023}, author = {Ponce, DM and Alousi, AM and Nakamura, R and Slingerland, J and Calafiore, M and Sandhu, KS and Barker, JN and Devlin, S and Shia, J and Giralt, S and Perales, MA and Moore, G and Fatmi, S and Soto, C and Gomes, A and Giardina, P and Marcello, L and Yan, X and Tang, T and Dreyer, K and Chen, J and Daley, WL and Peled, JU and van den Brink, MRM and Hanash, AM}, title = {A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract.}, journal = {Blood}, volume = {141}, number = {12}, pages = {1389-1401}, pmid = {36399701}, issn = {1528-0020}, support = {R01 AI101406/AI/NIAID NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 HL145631/HL/NHLBI NIH HHS/United States ; R01 HL146338/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Graft vs Host Disease/drug therapy/etiology ; Lower Gastrointestinal Tract ; Adrenal Cortex Hormones/therapeutic use ; Interleukin-22 ; }, abstract = {Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic transplantation. In experimental models, interleukin-22 promotes epithelial regeneration and induces innate antimicrobial molecules. We conducted a multicenter single-arm phase 2 study evaluating the safety and efficacy of a novel recombinant human interleukin-22 dimer, F-652, used in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD. The most common adverse events were cytopenias and electrolyte abnormalities, and there were no dose-limiting toxicities. Out of 27 patients, 19 (70%; 80% confidence interval, 56%-79%) achieved a day-28 treatment response, meeting the prespecified primary endpoint. Responders exhibited a distinct fecal microbiota composition characterized by expansion of commensal anaerobes, which correlated with increased overall microbial α-diversity, suggesting improvement of GVHD-associated dysbiosis. This work demonstrates a potential approach for combining immunosuppression with tissue-supportive strategies to enhance recovery of damaged mucosa and promote microbial health in patients with gastrointestinal GVHD. This trial was registered at www.clinicaltrials.gov as NCT02406651.}, }
@article {pmid36398264, year = {2022}, author = {Han, J and Zeng, A and Hou, Z and Xu, Y and Zhao, H and Wang, B and Guan, W and An, Y and Liang, S and Ma, Y}, title = {Identification of diagnostic markers related to fecal and plasma metabolism in primary Sjögren's syndrome.}, journal = {American journal of translational research}, volume = {14}, number = {10}, pages = {7378-7390}, pmid = {36398264}, issn = {1943-8141}, abstract = {BACKGROUND: Accurate diagnostic techniques for patients with primary Sjögren's syndrome (pSS) are needed. This study aimed to investigate new biomarkers related to fecal and plasma metabolism from pSS patients.<br><br>METHODS: The feces and plasma of 21 pSS patients and 18 controls admitted to the Second Hospital of Shanxi Medical University were collected for analysis. Metabolites in feces and plasma were quantified using liquid chromatography-mass spectrometry. The metabolic pathway alterations caused by pSS were studied and the expression of metabolites in the intersecting pathway was analyzed in the feces and plasma of pSS patients. Metabolites that showed the same alterations in feces and plasma in pSS patients were considered as diagnostic markers and receiver operating characteristic curves were generated to analyze the sensitivity of these markers in diagnosing pSS.<br><br>RESULTS: There were 114 and 92 upregulated metabolites and 54 and 125 downregulated metabolites in the feces and plasma of pSS patients, respectively. These metabolites were enriched in 8 pathways for feces and 12 pathways for plasma. Arginine biosynthesis, Linoleic acid metabolism, Tyrosine metabolism, Taurine and hypotaurine metabolism were pathways enriched by metabolites in both samples. Twelves metabolites were enriched in the above four pathways, while only 9,10-12,13-Diepoxyoctadecanoate, Tyramine, 9-OxoODE and 2-Hydroxyethanesulfonate showed the same trend. The candidate diagnostic markers were all predictive, with better diagnostic sensitivity in plasma samples.<br><br>CONCLUSIONS: 9,10-12,13-Diepoxyoctadecanoate, Tyramine, 9-OxoODE, 2-Hydroxyethanesulfonate were metabolism-related diagnostic markers for pSS feces and plasma.}, }
@article {pmid36396738, year = {2023}, author = {Ninkov, M and Schmerk, CL and Moradizadeh, M and Parvathy, SN and Figueredo, R and Burton, JP and Silverman, MS and Fernandes, R and Maleki Vareki, S and Haeryfar, SMM}, title = {Improved MAIT cell functions following fecal microbiota transplantation for metastatic renal cell carcinoma.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {72}, number = {5}, pages = {1247-1260}, pmid = {36396738}, issn = {1432-0851}, support = {Keith Samitt Translational Research Catalyst Grant//London Regional Cancer Program/ ; Innovation Grant 706396//Canadian Cancer Society/ ; }, mesh = {Humans ; Interleukin-18/metabolism ; *Carcinoma, Renal Cell/therapy/metabolism ; *Mucosal-Associated Invariant T Cells/metabolism ; Fecal Microbiota Transplantation ; *Kidney Neoplasms/therapy/metabolism ; Interleukin-12/metabolism ; }, abstract = {Strategies to modify the gut microbiome in cancer patients using fecal microbiota transplantation (FMT) have gained momentum as a therapeutic intervention. However, how FMT impacts innate-like, antimicrobial T lymphocytes is unclear. In this study, we assessed peripheral blood (PB) mucosa-associated invariant T (MAIT) cell frequencies and functions in patients with metastatic renal cell carcinoma (mRCC) before and seven days after they received FMT as part of a clinical trial. We found comparable MAIT cell frequencies in healthy controls and mRCC patients. In contrast, γδ T cells exhibited a numerical decline in mRCC, which was partially reversed by FMT. We also found a significant increase in the PB CD4[+] MAIT cell compartment of mRCC patients with or without FMT. Paired sample analyses revealed CD69 upregulation on MAIT cells accompanied by decreased PD-1 levels post-FMT. These changes were unique to MAIT cells as non-MAIT T lymphocytes showed either no trend or a trend in the opposite direction. Importantly, FMT did not render MAIT cells exhausted as also judged by their stable expression of TIM-3, LAG-3, BTLA, CTLA-4, TIGIT and VISTA. These findings were corroborated in functional assays in which MAIT cells were stimulated with MR1 ligands or with a combination of IL-12 and IL-18 to produce inflammatory cytokines and granzyme B. Indeed, when stimulated ex vivo with IL-12 and IL-18, MAIT cells mounted a more rigorous TNF-α response post-FMT. In conclusion, FMT improves MAIT cell functions, which should serve patients well in subsequent microbial challenges in the face of cancer-elicited immunosuppression. Trial Registration: https://clinicaltrials.gov/ Identifier: NCT04163289 (registration date: November 14, 2019).}, }
@article {pmid36395738, year = {2022}, author = {Zhang, W and Huang, J and Gao, F and You, Q and Ding, L and Gong, J and Zhang, M and Ma, R and Zheng, S and Sun, X and Zhang, Y}, title = {Lactobacillus reuteri normalizes altered fear memory in male Cntnap4 knockout mice.}, journal = {EBioMedicine}, volume = {86}, number = {}, pages = {104323}, pmid = {36395738}, issn = {2352-3964}, mesh = {Animals ; Male ; Mice ; Amygdala/metabolism ; *Autism Spectrum Disorder/genetics/microbiology ; Fear/physiology ; *Limosilactobacillus reuteri ; Membrane Proteins/genetics/metabolism ; Mice, Knockout ; Nerve Tissue Proteins/genetics/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Memory/physiology ; }, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disease, characterized by deficits in social communication, restricted and repetitive behaviours, and impaired fear memory processing. Severe gastrointestinal dysfunction and altered gut microbiome have been reported in ASD patients and animal models. Contactin associated protein-like 4 (CNTNAP4) has been suggested to be a novel risk gene, though its role in ASD remains unelucidated.<br><br>METHODS: Cntnap4[-/-] mice were generated to explore its role in ASD-related behavioural abnormalities. Electrophysiological recording was employed to examine GABAergic transmission in the basolateral amygdala (BLA) and prefrontal cortex. RNA-sequencing was performed to assess underlying mechanisms. 16S rDNA analysis was performed to explore changes in faecal microbial composition. Male Cntnap4[-/-] mice were fed with Lactobacillus reuteri (L.&#xa0;reuteri) or faecal microbiota to evaluate the effects of microbiota supplementation on the impaired fear conditioning mediated by Cntnap4 deficiency.<br><br>FINDINGS: Male Cntnap4[-/-] mice manifested deficiency in social behaviours and tone-cue fear conditioning. Notably, reduced GABAergic transmission and GABA receptor expression were found in the BLA but not the prefrontal cortex. In addition, gut Lactobacillus were less abundant in male Cntnap4[-/-] mice, and L.&#xa0;reuteri treatment or faecal microbiota transplantation rescued abnormal tone-cued fear memory and improved local GABAergic transmission in the BLA of male Cntnap4[-/-] mice.<br><br>INTERPRETATION: Cntnap4 shapes GABAergic transmission of amygdala and fear conditioning, and microbial intervention represents a promising therapy in ASD intervention.<br><br>FUNDING: National Natural Science Foundation of China, Science and Technology Planning Project of Guangzhou, Guangzhou Medical University, and China Postdoctoral Science Foundation.}, }
@article {pmid36394926, year = {2022}, author = {Fedotova, MM and Prokopyeva, VD and Dochkin, VA and Boguta, VD and Fedorova, OS}, title = {[Methods of gut microbiota correction for treatment and prevention of food allergy: a review of current research].}, journal = {Voprosy pitaniia}, volume = {91}, number = {5}, pages = {16-28}, doi = {10.33029/0042-8833-2022-91-5-16-28}, pmid = {36394926}, issn = {0042-8833}, mesh = {Humans ; Child ; *Gastrointestinal Microbiome ; *Food Hypersensitivity/prevention &amp; control ; Bifidobacterium ; Intestinal Mucosa ; Lactobacillus ; }, abstract = {Food allergy (FA) is an actual problem in pediatric practice. The gut microbiota plays a crucial role in food sensitization development, since the maturation of immune system occurs under the influence of intestinal microorganisms. Immunoregulatory activity of gut microbiota is associated with the increase of IgA production and promotion of the barrier function of intestinal epithelium. Gut microbiota influence the activity of T-regulatory cells, as well. Violation of gut biocenosis, which occurs under the influence of various factors (artificial feeding, past diseases, the use of antibiotics, etc.), can lead to a shift in the balance of the immune system towards the increase of Th2-profile cytokines and the subsequent formation of hypersensitivity to food allergens. In this regard, the correction of the gut microbiome is a promising method of FA control, due to the ability of intestinal bacteria influence the production of T-regulatory cells and thus suppress allergy immune response. The aim of the review is to analyze experimental and clinical studies exploring effectiveness of methods modifying intestinal microbiota in order to treat and prevent FA. Material and methods. The analysis of the literature in eLIBRARY, MedLine and PubMed databases was carried out. Results. The analysis revealed the lack of rigorous evidence that pre-, pro- and synbiotics significantly increase the effectiveness of standard therapy of FA. However, the use of bifidobacteria, lactobacilli, lactic acid bacteria, in combination with the basic therapy of FA has general positive effect on the clinical outcome, especially in case of gastrointestinal symptoms. Also, the results of some studies indicate the effectiveness of synbiotics (Bifidobacterium breve M-16V, Lactobacillus rhamnosus GG in combination with oligosaccharides) for the prevention of FA in patients at risk of developing allergic diseases in the long-term period. Conclusion. At present, fecal microbiota transplantation is promising method for FA treatment. Polysaccharides fermented by the microflora, are also actively studied. Experimental studies and clinical trials are required to obtain substantiated conclusions about feasibility of these methods for treatment and prevention of FA.}, }
@article {pmid36389774, year = {2022}, author = {Fujimoto, K and Uematsu, S}, title = {Phage therapy for Clostridioides difficile infection.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1057892}, pmid = {36389774}, issn = {1664-3224}, mesh = {Humans ; *Clostridioides difficile ; *Phage Therapy ; *Clostridium Infections/therapy/microbiology ; Fecal Microbiota Transplantation ; Diarrhea/therapy ; }, abstract = {Clostridioides difficile is endemic in the intestinal tract of healthy people. However, it is responsible for many healthcare-associated infections, such as nosocomial diarrhea following antibiotic treatment. Importantly, there have been cases of unsuccessful treatment and relapse related to the emergence of highly virulent strains of C. difficile and resistance to antimicrobial agents. Fecal microbiota transplantation (FMT) is considered an effective therapy for recurrent C. difficile infection. However, its safety is of concern because deaths caused by antibiotic-resistant bacterial infections after FMT were reported. Therefore, the development of effective C. difficile-specific treatments is urgently needed. In this review, we summarize the importance of phage therapy against C. difficile, and describe a novel next-generation phage therapy developed using metagenomic data.}, }
@article {pmid36389768, year = {2022}, author = {Zhou, G and Zhang, N and Meng, K and Pan, F}, title = {Interaction between gut microbiota and immune checkpoint inhibitor-related colitis.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1001623}, pmid = {36389768}, issn = {1664-3224}, mesh = {Humans ; Immune Checkpoint Inhibitors/adverse effects ; *Gastrointestinal Microbiome ; *Colitis/chemically induced/therapy ; Fecal Microbiota Transplantation ; *Neoplasms ; }, abstract = {Immune checkpoint inhibitors (ICIs) have become a promising therapeutic strategy for malignant tumors, improving patient prognosis, along with a spectrum of immune-related adverse events (irAEs), including gastrointestinal toxicity, ICI-related colitis (IRC), and diarrhea. The gut microbiota has been suggested as an important regulator in the pathogenesis of IRC, and microbiota modulations like probiotics and fecal microbiota transplantation have been explored to treat the disease. This review discusses the interaction between the gut microbiota and IRC, focusing on the potential pathogenic mechanisms and promising interventions.}, }
@article {pmid36389714, year = {2022}, author = {Zou, X and Wang, L and Xiao, L and Wang, S and Zhang, L}, title = {Gut microbes in cerebrovascular diseases: Gut flora imbalance, potential impact mechanisms and promising treatment strategies.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {975921}, pmid = {36389714}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Cerebrovascular Disorders/therapy ; Brain/metabolism ; *Microbiota ; Bacteria ; }, abstract = {The high morbidity, mortality, and disability rates associated with cerebrovascular disease (CeVD) pose a severe danger to human health. Gut bacteria significantly affect the onset, progression, and prognosis of CeVD. Gut microbes play a critical role in gut-brain interactions, and the gut-brain axis is essential for communication in CeVD. The reflection of changes in the gut and brain caused by gut bacteria makes it possible to investigate early warning biomarkers and potential treatment targets. We primarily discussed the following three levels of brain-gut interactions in a systematic review of the connections between gut microbiota and several cerebrovascular conditions, including ischemic stroke, intracerebral hemorrhage, intracranial aneurysm, cerebral small vessel disease, and cerebral cavernous hemangioma. First, we studied the gut microbes in conjunction with CeVD and examined alterations in the core microbiota. This enabled us to identify the focus of gut microbes and determine the focus for CeVD prevention and treatment. Second, we discussed the pathological mechanisms underlying the involvement of gut microbes in CeVD occurrence and development, including immune-mediated inflammatory responses, variations in intestinal barrier function, and reciprocal effects of microbial metabolites. Finally, based on the aforementioned proven mechanisms, we assessed the effectiveness and potential applications of the current therapies, such as dietary intervention, fecal bacterial transplantation, traditional Chinese medicine, and antibiotic therapy.}, }
@article {pmid36389141, year = {2022}, author = {Dong, W and Zheng, J and Huang, Y and Tan, H and Yang, S and Zhang, Z and Liang, X and Liu, H and Zeng, G and Xu, H and Jiang, X and Zhong, W}, title = {Sodium butyrate treatment and fecal microbiota transplantation provide relief from ulcerative colitis-induced prostate enlargement.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1037279}, pmid = {36389141}, issn = {2235-2988}, mesh = {Humans ; Male ; Mice ; Animals ; Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy ; Butyric Acid ; *Prostatic Hyperplasia/therapy ; Prostate ; *Gastrointestinal Microbiome ; }, abstract = {The ability to regulate the gut environment has resulted in remarkable great breakthroughs in the treatment of several diseases. Several studies have found that the regulation of the gut environment might provide relief from the symptoms of benign prostatic hyperplasia. However, the correlation between the gut microenvironment and the colon and prostate glands is still unknown. We found that ulcerative colitis (UC) induced an increase in prostate volumes that could be reversed by sodium butyrate (NaB) and fecal microbiota transplantation (FMT). The mechanism by which UC induced changes in the prostate gland was examined via RNA-Seq. The results show that the expression level of GPER was significantly lower in the prostate gland of UC mices than in normal mices. The expression of GPER could be increased via treatment with NaB or FMT. We found that prostate tissues exhibited higher butryic acid levels after they were treated with NaB or FMT. In experiments conducted in vitro, NaB or the fecal filtrate (FF) from healthy mice up-regulated of the expression of GPER, inhibited cell growth, and induced apoptosis in BPH-1 cells. These changes could be alleviated by treatment with the G15 or in GPER-silenced cells.}, }
@article {pmid36387852, year = {2022}, author = {Acharya, KD and Friedline, RH and Ward, DV and Graham, ME and Tauer, L and Zheng, D and Hu, X and de Vos, WM and McCormick, BA and Kim, JK and Tetel, MJ}, title = {Differential effects of Akkermansia-enriched fecal microbiota transplant on energy balance in female mice on high-fat diet.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {1010806}, pmid = {36387852}, issn = {1664-2392}, support = {U24 DK076169/DK/NIDDK NIH HHS/United States ; R01 DK061935/DK/NIDDK NIH HHS/United States ; U2C DK093000/DK/NIDDK NIH HHS/United States ; R01 DK109677/DK/NIDDK NIH HHS/United States ; R01 DK125407/DK/NIDDK NIH HHS/United States ; }, mesh = {Female ; Mice ; Male ; Animals ; *Diet, High-Fat/adverse effects ; Akkermansia ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Obesity/etiology/therapy/metabolism ; Weight Gain ; *Hyperglycemia ; }, abstract = {Estrogens protect against weight gain and metabolic disruption in women and female rodents. Aberrations in the gut microbiota composition are linked to obesity and metabolic disorders. Furthermore, estrogen-mediated protection against diet-induced metabolic disruption is associated with modifications in gut microbiota. In this study, we tested if estradiol (E2)-mediated protection against obesity and metabolic disorders in female mice is dependent on gut microbiota. Specifically, we tested if fecal microbiota transplantation (FMT) from E2-treated lean female mice, supplemented with or without Akkermansia muciniphila, prevented high fat diet (HFD)-induced body weight gain, fat mass gain, and hyperglycemia in female recipients. FMT from, and cohousing with, E2-treated lean donors was not sufficient to transfer the metabolic benefits to the E2-deficient female recipients. Moreover, FMT from lean donors supplemented with A. muciniphila exacerbated HFD-induced hyperglycemia in E2-deficient recipients, suggesting its detrimental effect on the metabolic health of E2-deficient female rodents fed a HFD. Given that A. muciniphila attenuates HFD-induced metabolic insults in males, the present findings suggest a sex difference in the impact of this microbe on metabolic health.}, }
@article {pmid36386919, year = {2022}, author = {Liu, TH and Zhao, L and Zhang, CY and Li, XY and Wu, TL and Dai, YY and Sheng, YY and Ren, YL and Xue, YZ}, title = {Gut microbial evidence chain in high-salt diet exacerbates intestinal aging process.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {1046833}, pmid = {36386919}, issn = {2296-861X}, abstract = {Although excessive salt consumption appears to hasten intestinal aging and increases susceptibility to cardiovascular disease, the molecular mechanism is unknown. In this study, mutual validation of high salt (HS) and aging fecal microbiota transplantation (FMT) in C56BL/6 mice was used to clarify the molecular mechanism by which excessive salt consumption causes intestinal aging. Firstly, we observed HS causes vascular endothelial damage and can accelerate intestinal aging associated with decreased colon and serum expression of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and increased malondialdehyde (MDA); after transplantation with HS fecal microbiota in mice, vascular endothelial damage and intestinal aging can also occur. Secondly, we also found intestinal aging and vascular endothelial damage in older mice aged 14 months; and after transplantation of the older mice fecal microbiota, the same effect was observed in mice aged 6-8 weeks. Meanwhile, HS and aging significantly changed gut microbial diversity and composition, which was transferable by FMT. Eventually, based on the core genera both in HS and the aging gut microbiota network, a machine learning model was constructed which could predict HS susceptibility to intestinal aging. Further investigation revealed that the process of HS-related intestinal aging was highly linked to the signal transduction mediated by various bacteria. In conclusion, the present study provides an experimental basis of potential microbial evidence in the process of HS related intestinal aging. Even, avoiding excessive salt consumption and actively intervening in gut microbiota alteration may assist to delay the aging state that drives HS-related intestinal aging in clinical practice.}, }
@article {pmid36384941, year = {2023}, author = {Lane, VA and Lall, A and Jaffray, B}, title = {Single institution experience of cloacal malformation.}, journal = {Journal of pediatric surgery}, volume = {58}, number = {2}, pages = {270-274}, doi = {10.1016/j.jpedsurg.2022.10.035}, pmid = {36384941}, issn = {1531-5037}, mesh = {Female ; Animals ; Humans ; Infant ; *Cloaca/surgery ; Retrospective Studies ; *Vagina/surgery/abnormalities ; Rectum/surgery ; Urethra/surgery ; }, abstract = {INTRODUCTION: The aim of this study is to report on the outcomes of patients born with cloacal malformation, managed at a single institution more than the last 28 years. The focus of this study is the long term renal and colorectal outcomes.<br><br>METHODS: Patients were identified from the departmental database from 1994 to 2021. The medical records and operative notes were retrospectively reviewed.<br><br>RESULTS: Twenty-one patients fulfilled the inclusion criteria. Eleven long common channel (LCC) and ten short common channel (SCC) cloacae patients were identified. Median age at the time of primary reconstruction was 11 months in both groups. In the LCC group, seven (63.6%) patients underwent a Total Urogenital Mobilisation (TUM), and 4 (36.4%) required a vaginal replacement. 6/11 (54.5%) of patients required drainage of a hydrocolpos. In the SCC group, four patients required a TUM, two patients underwent mobilisation of the rectum and vagina alone, and three underwent rectal mobilisation alone. Two patients have required renal transplant for congenital renal dysplasia, and two have developed chronic renal failure associated with the sequalae of vesicoureteric reflux. Eleven (52.3%) of the patients manage their bowels with an antegrade continent enema (ACE), and two of the LCC cloaca are defunctioned with a colostomy. Clean intermittent catheterisation is performed by 12 (57%) of the patients, either per urethra or via a Mitrofanoff channel.<br><br>CONCLUSION: The urinary and faecal continence are the main challenges in the management of cloaca patients. Many require surgical intervention to achieve social continence.<br><br>LEVEL OF EVIDENCE: Level IV.}, }
@article {pmid36383683, year = {2022}, author = {Schwabkey, ZI and Wiesnoski, DH and Chang, CC and Tsai, WB and Pham, D and Ahmed, SS and Hayase, T and Ortega Turrubiates, MR and El-Himri, RK and Sanchez, CA and Hayase, E and Frenk Oquendo, AC and Miyama, T and Halsey, TM and Heckel, BE and Brown, AN and Jin, Y and Raybaud, M and Prasad, R and Flores, I and McDaniel, L and Chapa, V and Lorenzi, PL and Warmoes, MO and Tan, L and Swennes, AG and Fowler, S and Conner, M and McHugh, K and Graf, T and Jensen, VB and Peterson, CB and Do, KA and Zhang, L and Shi, Y and Wang, Y and Galloway-Pena, JR and Okhuysen, PC and Daniel-MacDougall, CR and Shono, Y and Burgos da Silva, M and Peled, JU and van den Brink, MRM and Ajami, N and Wargo, JA and Reddy, P and Valdivia, RH and Davey, L and Rondon, G and Srour, SA and Mehta, RS and Alousi, AM and Shpall, EJ and Champlin, RE and Shelburne, SA and Molldrem, JJ and Jamal, MA and Karmouch, JL and Jenq, RR}, title = {Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment.}, journal = {Science translational medicine}, volume = {14}, number = {671}, pages = {eabo3445}, pmid = {36383683}, issn = {1946-6242}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; K01 AI143881/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; S10 OD012304/OD/NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Propionates ; *Hematopoietic Stem Cell Transplantation ; Verrucomicrobia ; Mucus/metabolism ; Mucins/metabolism ; Diet ; *Neutropenia/metabolism ; *Neoplasms/metabolism ; }, abstract = {Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing hematopoietic cell transplant (n = 119), the fecal microbiome was characterized at onset of severe neutropenia. A total of 63 patients (53%) developed a subsequent fever, and their fecal microbiome displayed increased relative abundances of Akkermansia muciniphila, a species of mucin-degrading bacteria (P = 0.006, corrected for multiple comparisons). Two therapies that induce neutropenia, irradiation and melphalan, similarly expanded A. muciniphila and additionally thinned the colonic mucus layer in mice. Caloric restriction of unirradiated mice also expanded A. muciniphila and thinned the colonic mucus layer. Antibiotic treatment to eradicate A. muciniphila before caloric restriction preserved colonic mucus, whereas A. muciniphila reintroduction restored mucus thinning. Caloric restriction of unirradiated mice raised colonic luminal pH and reduced acetate, propionate, and butyrate. Culturing A. muciniphila in vitro with propionate reduced utilization of mucin as well as of fucose. Treating irradiated mice with an antibiotic targeting A. muciniphila or propionate preserved the mucus layer, suppressed translocation of flagellin, reduced inflammatory cytokines in the colon, and improved thermoregulation. These results suggest that diet, metabolites, and colonic mucus link the microbiome to neutropenic fever and may guide future microbiome-based preventive strategies.}, }
@article {pmid36382711, year = {2023}, author = {Tian, D and Xu, W and Pan, W and Zheng, B and Yang, W and Jia, W and Liu, Y and Garstka, MA and Gao, Y and Yu, H}, title = {Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA-induced MEK1/2 signaling pathway.}, journal = {The EMBO journal}, volume = {42}, number = {1}, pages = {e111139}, pmid = {36382711}, issn = {1460-2075}, mesh = {Rats ; Animals ; *Fecal Microbiota Transplantation ; *Hirschsprung Disease/therapy/genetics/metabolism ; Signal Transduction ; Fatty Acids, Volatile/metabolism ; Cell- and Tissue-Based Therapy ; }, abstract = {Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which causes severe complications. Enteric neural crest-derived cell (ENCC) transplantation is a potential therapeutic strategy; however, so far with poor efficacy. Here, we assessed whether and how fecal microbiota transplantation (FMT) could improve ENCC transplantation in a rat model of hypoganglionosis; a condition similar to HSCR, with less intestinal innervation. We found that the hypoganglionosis intestinal microenvironment negatively influenced the ENCC functional phenotype in vitro and in vivo. Combining 16S rDNA sequencing and targeted mass spectrometry revealed microbial dysbiosis and reduced short-chain fatty acid (SCFA) production in the hypoganglionic gut. FMT increased the abundance of Bacteroides and Clostridium, SCFA production, and improved outcomes following ENCC transplantation. SCFAs alone stimulated ENCC proliferation, migration, and supported ENCC transplantation. Transcriptome-wide mRNA sequencing identified MAPK signaling as the top differentially regulated pathway in response to SCFA exposure, and inhibition of MEK1/2 signaling abrogated the SCFA-mediated effects on ENCC. This study demonstrates that FMT improves cell therapy for hypoganglionosis via short-chain fatty acid metabolism-induced MEK1/2 signaling.}, }
@article {pmid36382190, year = {2022}, author = {Fang, X and Miao, R and Wei, J and Wu, H and Tian, J}, title = {Advances in multi-omics study of biomarkers of glycolipid metabolism disorder.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {5935-5951}, pmid = {36382190}, issn = {2001-0370}, abstract = {Glycolipid metabolism disorder are major threats to human health and life. Genetic, environmental, psychological, cellular, and molecular factors contribute to their pathogenesis. Several studies demonstrated that neuroendocrine axis dysfunction, insulin resistance, oxidative stress, chronic inflammatory response, and gut microbiota dysbiosis are core pathological links associated with it. However, the underlying molecular mechanisms and therapeutic targets of glycolipid metabolism disorder remain to be elucidated. Progress in high-throughput technologies has helped clarify the pathophysiology of glycolipid metabolism disorder. In the present review, we explored the ways and means by which genomics, transcriptomics, proteomics, metabolomics, and gut microbiomics could help identify novel candidate biomarkers for the clinical management of glycolipid metabolism disorder. We also discuss the limitations and recommended future research directions of multi-omics studies on these diseases.}, }
@article {pmid36381829, year = {2022}, author = {Nassar, ST and Tasha, T and Desai, A and Bajgain, A and Ali, A and Dutta, C and Pasha, K and Paul, S and Abbas, MS and Venugopal, S}, title = {Fecal Microbiota Transplantation Role in the Treatment of Alzheimer's Disease: A Systematic Review.}, journal = {Cureus}, volume = {14}, number = {10}, pages = {e29968}, pmid = {36381829}, issn = {2168-8184}, abstract = {Alzheimer's, a neurodegenerative disease that starts slowly and worsens progressively, is the leading cause of dementia worldwide. Recent studies have linked the brain with the gut and its microbiota through the microbiota-gut-brain axis, opening the door for gut-modifying agents (e.g., prebiotics and probiotics) to influence our brain's cognitive function. This review aims to identify and summarize the effects of fecal microbiota transplantation (FMT) as a gut-microbiota-modifying agent on the progressive symptoms of Alzheimer's disease (AD). This systematic review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A systematic search was done using Google Scholar, PubMed, PubMed Central, and ScienceDirect databases in June 2022. The predefined criteria upon which the studies were selected are English language, past 10 years of narrative reviews, observational studies, case reports, and animal studies involving Alzheimer's subjects as no previous meta-analysis or systematic reviews were done on this subject. Later, a quality assessment was done using the available assessment tool based on each study type. The initial search generated 4,302 studies, yielding 13 studies to be included in the final selection: 1 cohort, 2 case reports, 2 animal studies, and 8 narrative reviews. Our results showed that FMT positively affected AD subjects (whether mice or humans). In humans, the FMT effect was measured by the Mini-Mental State Examination (MMSE), showing improvement in Alzheimer's symptoms of mood, memory, and cognition. However, randomized and nonrandomized clinical trials are essential for more conclusive results.}, }
@article {pmid36380385, year = {2022}, author = {Yan, J and Pan, Y and Shao, W and Wang, C and Wang, R and He, Y and Zhang, M and Wang, Y and Li, T and Wang, Z and Liu, W and Wang, Z and Sun, X and Dong, S}, title = {Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {195}, pmid = {36380385}, issn = {2049-2618}, mesh = {Rats ; Animals ; *Gastrointestinal Microbiome/physiology ; Propionates ; Fatty Acids, Volatile ; Verrucomicrobia ; *Vascular Calcification/drug therapy ; }, abstract = {BACKGROUND: Vascular calcification is a major cause of the high morbidity and mortality of cardiovascular diseases and is closely associated with the intestinal microbiota. Short-chain fatty acids (SCFAs) are derived from the intestinal microbiota and can also regulate intestinal microbiota homeostasis. However, it remains unclear whether exogenous supplementation with propionate, a SCFA, can ameliorate vascular calcification by regulating the intestinal microbiota. This study was conducted to explore the roles of propionate and the intestinal microbiota in the process of vascular calcification.<br><br>METHODS: In total, 92 patients were enrolled consecutively as the observational cohort to analyse the relationship between SCFAs and vascular calcification in both blood and faecal samples. A rat model of vascular calcification was induced by vitamin D3 and nicotine (VDN) to validate the effect of propionate. Differences in the intestinal microbiota were analysed by 16S ribosomal RNA gene sequencing. Faecal microbiota transplantation and Akkermansia muciniphila transplantation experiments were performed to evaluate the functions of the intestinal microbiota.<br><br>RESULTS: The results of the observational cohort study revealed that the levels of SCFAs (particularly propionate) in both blood and faecal samples independently correlated negatively with calcification scores (P < 0.01). To verify the activities of propionate, it was provided to VDN-treated rats, and oral or rectal propionate delivery reshaped the intestinal microbiota, resulted in elevated SCFA production, improved intestinal barrier function and alleviated inflammation, ultimately ameliorating vascular calcification. Furthermore, we demonstrated that transplantation of the propionate-modulated intestinal microbiota induced beneficial outcomes similar to those with oral or rectal propionate administration. Interestingly, linear discriminant analysis (LDA) effect size (LEfSe) revealed that oral or rectal propionate administration and propionate-modulated intestinal microbiota transplantation both enriched primarily Akkermansia. Subsequently, we demonstrated that Akkermansia supplementation could ameliorate VDN-induced vascular calcification in rats.<br><br>CONCLUSIONS: Propionate can significantly ameliorate vascular calcification in VDN-treated rats, and this effect is mediated by intestinal microbiota remodelling. The findings in our study indicate that the intestinal tract-vessel axis is a promising target for alleviating vascular calcification. Video Abstract.}, }
@article {pmid36380056, year = {2022}, author = {Zhang, C and Shi, Y and Burch, M and Olthoff, B and Ericsson, AC and Franklin, CL}, title = {Transfer efficiency and impact on disease phenotype of differing methods of gut microbiota transfer.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {19621}, pmid = {36380056}, issn = {2045-2322}, support = {U42 OD010918/OD/NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/genetics ; Fecal Microbiota Transplantation/methods ; *Colitis/chemically induced/genetics ; Phenotype ; *Microbiota ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {To test causal relationships between complex gut microbiota (GM) and host outcomes, researchers frequently transfer GM between donor and recipient mice via embryo transfer (ET) rederivation, cross-fostering (CF), and co-housing. In this study, we assess the influence of the transfer method and the differences in baseline donor and recipient microbiota richness, on transfer efficiency. Additionally, recipient mice were subjected to DSS-induced chronic colitis to determine whether disease severity was affected by GM transfer efficiency or features within the GM. We found that the recipient's genetic background, the baseline richness of donor and recipient GM, and the transfer method all influenced the GM transfer efficiency. Recipient genetic background and GM both had significant effects on DSS colitis severity and, unexpectedly, the transfer method was strongly associated with differential disease severity regardless of the other factors.}, }
@article {pmid36380005, year = {2022}, author = {Lordick, F and Hacker, U and Hoffmeister, A and Bläker, H and Gockel, I}, title = {[What is confirmed in the treatment of colon cancer?].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {12}, pages = {1250-1256}, pmid = {36380005}, issn = {2731-7099}, mesh = {Male ; Female ; Humans ; *Colorectal Neoplasms/diagnosis ; Colonoscopy ; Occult Blood ; *Colonic Neoplasms/diagnosis ; *Adenoma/diagnosis ; }, abstract = {Colorectal cancer is the second most common cancer diagnosed in Germany and is the third most frequent cause of cancer-related death in both males and females. The majority of colorectal cancers occur via the adenoma-carcinoma sequence of origin. This means that colorectal cancers can be endoscopically detected in premalignant stages and can be curatively treated within the framework of early detection. Screening colonoscopy and, to a lesser extent, fecal occult blood testing, have led to a reduction in the colon cancer-related incidence and mortality. The acceptance and the use of screening colonoscopy should therefore be developed further. Treatment strategies for colorectal cancer are based on TNM staging, supplemented by anatomical and histopathological risk features as well as individual patient characteristics and treatment preferences. The molecular tumor profile is increasingly used to complement decision-making in the surgical, adjuvant and palliative treatment of colorectal cancer. Colon and rectal cancer have many similarities; however, they differ in the preoperative, surgical and adjuvant treatment strategies. This article focuses on colon cancer.}, }
@article {pmid36378195, year = {2022}, author = {Liu, X and Zhang, Y and Li, W and Zhang, B and Yin, J and Liuqi, S and Wang, J and Peng, B and Wang, S}, title = {Fucoidan Ameliorated Dextran Sulfate Sodium-Induced Ulcerative Colitis by Modulating Gut Microbiota and Bile Acid Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {70}, number = {47}, pages = {14864-14876}, doi = {10.1021/acs.jafc.2c06417}, pmid = {36378195}, issn = {1520-5118}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Dextran Sulfate/adverse effects ; *Colitis, Ulcerative/chemically induced/drug therapy ; Disease Models, Animal ; *Colitis/chemically induced/drug therapy/metabolism ; Colon/metabolism ; Inflammation/pathology ; Ursodeoxycholic Acid ; Mice, Inbred C57BL ; }, abstract = {Gut dysbiosis and bile acid (BA) metabolism disturbance are involved in the pathogenesis of ulcerative colitis. This study aimed to investigate the effect of fucoidan on BA metabolism and gut microbiota in dextran sulfate sodium-induced colitis mice. Our results showed that fucoidan effectively suppressed colonic inflammation and repaired the gut barrier. In addition, fucoidan increased the relative abundance of the Lachnospiraceae family, such as Turicibacter, Muribaculum, Parasutterella, and Colidextribacter, followed by an increase in short-chain fatty acids, especially in butyrate. Moreover, fucoidan modulated bile acid metabolism by elevating cholic acid, ursodeoxycholic acid, deoxycholic acid, and lithocholic acid and decreasing β-muricholic acid, which led to activation of FXR and TGR5 and further enhanced the gut barrier and suppressed colonic inflammation. Our results revealed that the effect of fucoidan alleviating colitis was largely mediated by gut microbiota, which was confirmed by the fecal transplantation experiment. Collectively, these findings provided the basis for fucoidan as a potential functional food for colitis.}, }
@article {pmid36376894, year = {2022}, author = {Zhu, H and Li, G and Liu, J and Xu, X and Zhang, Z}, title = {Gut microbiota is associated with the effect of photoperiod on seasonal breeding in male Brandt's voles (Lasiopodomys brandtii).}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {194}, pmid = {36376894}, issn = {2049-2618}, mesh = {Animals ; Humans ; Male ; Photoperiod ; *Gastrointestinal Microbiome/genetics ; *Melatonin/metabolism ; Seasons ; Arvicolinae/physiology ; }, abstract = {BACKGROUND: Seasonal breeding in mammals has been widely recognized to be regulated by photoperiod, but the association of gut microbiota with photoperiodic regulation of seasonal breeding has never been investigated.<br><br>RESULTS: In this study, we investigated the association of gut microbiota with photoperiod-induced reproduction in male Brandt's voles (Lasiopodomys brandtii) through a long-day and short-day photoperiod manipulation experiment and fecal microbiota transplantation (FMT) experiment. We found photoperiod significantly altered reproductive hormone and gene expression levels, and gut microbiota of voles. Specific gut microbes were significantly associated with the reproductive hormones and genes of voles during photoperiod acclimation. Transplantation of gut microbes into recipient voles induced similar changes in three hormones (melatonin, follicle-stimulating hormone, and luteinizing hormone) and three genes (hypothalamic Kiss-1, testicular Dio3, and Dio2/Dio3 ratio) to those in long-day and short-day photoperiod donor voles and altered circadian rhythm peaks of recipient voles.<br><br>CONCLUSIONS: Our study firstly revealed the association of gut microbiota with photoperiodic regulation of seasonal breeding through the HPG axis, melatonin, and Kisspeptin/GPR54 system. Our results may have significant implications for pest control, livestock animal breeding, and human health management. Video Abstract.}, }
@article {pmid36376576, year = {2023}, author = {Piovezani Ramos, G and Camilleri, M}, title = {Current and Future Therapeutic Options for Irritable Bowel Syndrome with Diarrhea and Functional Diarrhea.}, journal = {Digestive diseases and sciences}, volume = {68}, number = {5}, pages = {1677-1690}, pmid = {36376576}, issn = {1573-2568}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/drug therapy ; Quality of Life ; Diarrhea/drug therapy/etiology ; Rifaximin/therapeutic use ; Gastrointestinal Agents/therapeutic use ; Bile Acids and Salts ; }, abstract = {Irritable bowel syndrome with diarrhea and functional diarrhea are disorders of gut-brain interaction presenting with chronic diarrhea; they have significant impact on quality of life. The two conditions may exist as a continuum and their treatment may overlap. Response to first-line therapy with antispasmodics and anti-diarrheal agents is variable, leaving several patients with suboptimal symptom control and need for alternative therapeutic options. Our aim was to discuss current pharmacologic options and explore alternative therapeutic approaches and future perspectives for symptom management in irritable bowel syndrome with diarrhea and functional diarrhea. We conducted a search of PubMed, Cochrane, clinicaltrial.gov, major meeting abstracts for publications on current, alternative, and emerging drugs for irritable bowel syndrome with diarrhea and functional diarrhea. Currently approved therapeutic options for patients with first-line refractory irritable bowel syndrome with diarrhea and functional diarrhea include serotonin-3 receptor antagonists, eluxadoline and rifaximin. Despite their proven efficacy, cost and availability worldwide impact their utilization. One-third of patients with disorders of gut-brain interaction with diarrhea have bile acid diarrhea and may benefit from drugs targeting bile acid synthesis and excretion. Further understanding of underlying pathophysiology of irritable bowel syndrome with diarrhea and functional diarrhea related to bile acid metabolism, gastrointestinal transit, and microbiome has led to evaluation of novel therapeutic approaches, including fecal microbiota transplantation and enterobacterial "crapsules". These opportunities to treat disorders of gut-brain interaction with diarrhea should be followed with formal studies utilizing large samples of well-characterized patients at baseline and validated response outcomes as endpoints for regulatory approval.}, }
@article {pmid36372864, year = {2023}, author = {Weingarden, AR and Treiger, O and Ulsh, L and Limketkai, B and Goldenberg, D and Okafor, P and Sonu, I and Stollman, N and Neshatian, L}, title = {Delivery of Fecal Material to Terminal Ileum Is Associated with Long-Term Success of Fecal Microbiota Transplantation.}, journal = {Digestive diseases and sciences}, volume = {68}, number = {5}, pages = {2006-2014}, pmid = {36372864}, issn = {1573-2568}, support = {T32 DK007056/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects/methods ; *Clostridioides difficile ; Recurrence ; Feces ; Treatment Outcome ; *Clostridium Infections/therapy ; Ileum ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (CDI). However, 10-20% of patients still fail to recover following FMT. There is a need to understand why these failures occur and if there are modifiable factors that can be addressed by clinicians performing FMT.<br><br>AIMS: We sought to identify factors related to the FMT procedure itself which could impact FMT outcomes. We also aimed to identify patient demographics which might be associated with FMT outcomes and whether any factors were associated with early FMT failure compared to late CDI recurrence.<br><br>METHODS: We performed a retrospective multicenter cohort analysis of FMT procedures between October 2005 and November 2020. We collected data on patient demographics, details of the FMT procedure, and procedure outcomes. Using univariate and multivariate regression, we evaluated whether these factors were associated with long-term FMT success, early FMT failure (less than 60&#xa0;days following procedure), or late CDI recurrence (more than 60&#xa0;days following procedure).<br><br>RESULTS: Long-term success of FMT was strongly correlated with any delivery of stool to the terminal ileum (Odds Ratio [OR] 4.83, 95% confidence interval [CI] 1.359-17.167) and underlying neurologic disease (OR 8.012, 95% CI 1.041-61.684). Lower bowel prep quality was significantly associated with both early FMT failure (p&#x2009;=&#x2009;0.034) and late CDI recurrence (p&#x2009;=&#x2009;0.050).<br><br>CONCLUSIONS: Delivery of stool to the terminal ileum is significantly associated with long-term success following FMT. This is a relatively safe practice which could easily be incorporated into the standard of care for colonoscopic FMT.}, }
@article {pmid36372205, year = {2023}, author = {Xiang, Q and Yan, X and Shi, W and Li, H and Zhou, K}, title = {Early gut microbiota intervention in premature infants: Application perspectives.}, journal = {Journal of advanced research}, volume = {51}, number = {}, pages = {59-72}, pmid = {36372205}, issn = {2090-1224}, mesh = {Infant ; Female ; Child ; Infant, Newborn ; Humans ; *Gastrointestinal Microbiome ; Dysbiosis/therapy ; *Premature Birth ; Infant, Premature ; Gastrointestinal Tract ; }, abstract = {BACKGROUND: Preterm birth is the leading cause of death in children under the age of five. One of the major factors contributing to the high risk of diseases and deaths in premature infants is the incomplete development of the intestinal immune system. The gut microbiota has been widely recognized as a critical factor in promoting the development and function of the intestinal immune system after birth. However, the gut microbiota of premature infants is at high risk of dysbiosis, which is highly associated with adverse effects on the development and education of the early life immune system. Early intervention can modulate the colonization and development of gut microbiota and has a long-term influence on the development of the intestinal immune system.<br><br>AIM OF REVIEW: This review aims to summarize the characterization, interconnection, and underlying mechanism of gut microbiota and intestinal innate immunity in premature infants, and to discuss the status, applicability, safety, and prospects of different intervention strategies in premature infants, thus providing an overview and outlook of the current applications and remaining gaps of early intervention strategies in premature infants.<br><br>This review is focused on three key concepts. Firstly, the gut microbiota of premature infants is at high risk of dysbiosis, resulting in dysfunctional intestinal immune system processes. Secondly, contributing roles of early intervention have been observed in improving the intestinal environment and promoting gut microbiota colonization, which is significant in the development and function of gut immunity in premature infants. Thirdly, different strategies of early intervention, such as probiotics, fecal microbiota transplantation, and nutrients, show different safety, applicability, and outcome in premature infants, and the underlying mechanism is complex and poorly understood.}, }
@article {pmid36371983, year = {2022}, author = {Yao, Y and Sun, S and Gu, J and Ni, H and Zhong, K and Xu, Q and Zhou, D and Wang, X and Gao, L and Zhu, X}, title = {Roux-en-Y reconstruction alleviates radical gastrectomy-induced colitis via down-regulation of the butyrate/NLRP3 signaling pathway.}, journal = {EBioMedicine}, volume = {86}, number = {}, pages = {104347}, pmid = {36371983}, issn = {2352-3964}, mesh = {Animals ; Mice ; Butyrates/metabolism ; *Colitis/etiology/metabolism ; Diabetes Mellitus, Type 2/surgery ; Down-Regulation ; *Gastrectomy/adverse effects/methods ; Inflammasomes ; Inflammation ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; RNA, Ribosomal, 16S ; Signal Transduction ; Stomach Neoplasms/surgery ; Treatment Outcome ; *Anastomosis, Roux-en-Y/methods/veterinary ; }, abstract = {BACKGROUND: Different methods for digestive tract reconstruction have a complex impact on the nutritional status of gastric cancer (GC) patients after radical gastrectomy. Previous studies reported that Roux-en-Y (R-Y) reconstruction resulted in obvious weight reduction and improvement in type 2 diabetes in obese patients. We investigated the relationship between R-Y reconstruction, gut microbiota, and the NLRP3 inflammasome in GC patients with poor basic nutrition.<br><br>METHODS: Changes in the gut microbiota after radical gastrectomy accomplished by different methods of digestive tract reconstruction were investigated via fecal microbiota transplantation. The underlying mechanisms were also explored by analyzing the role of the microbiota, butyrate, and the NLRP3 inflammasome in the colon tissues of colitis model mice and GC patients after radical gastrectomy.<br><br>FINDINGS: R-Y reconstruction effectively relieved intestinal inflammation and facilitated nutrient absorption. 16S rRNA analysis revealed that gavage transplantation with the fecal microbiota of R-Y reconstruction patients could reverse dysbacteriosis triggered by radical gastrectomy and elevate the relative abundance of some short-chain fatty acid (SCFA)-producing bacteria. Subsequently, butyrate negatively regulated the NLRP3-mediated inflammatory signaling pathway to inhibit the activation of macrophages and the secretion of pro-inflammatory mediators such as caspase-1 and interleukin (IL)-1&#x3b2;, decreasing the level of intestinal inflammation and promoting nutrient absorption.<br><br>INTERPRETATION: R-Y reconstruction induced colonization with SCFA-producing bacteria to alleviate radical gastrectomy-induced colitis by down-regulating the NLRP3 signaling pathway. This can be a new strategy and theoretical basis for the management of the postoperative nutritional status of GC patients.<br><br>FUNDING: This work was supported by the National Nature Science Foundation of China (81974375), the BoXi cultivation program (BXQN202130), and the Project of Youth Foundation in Science and Education of the Department of Public Health of Suzhou (KJXW2018001).}, }
@article {pmid36369072, year = {2022}, author = {Gu, J and Ji, H and Liu, T and Chen, C and Zhao, S and Cao, Y and Wang, N and Xiao, M and Chen, L and Cai, H}, title = {Detection of cytomegalovirus (CMV) by digital PCR in stool samples for the non-invasive diagnosis of CMV gastroenteritis.}, journal = {Virology journal}, volume = {19}, number = {1}, pages = {183}, pmid = {36369072}, issn = {1743-422X}, mesh = {Humans ; Cytomegalovirus/genetics ; Retrospective Studies ; *Cytomegalovirus Infections/diagnosis ; *Graft vs Host Disease/complications ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Polymerase Chain Reaction ; *Enteritis ; *Enterovirus Infections/complications ; *Cell-Free Nucleic Acids ; }, abstract = {BACKGROUND: CMV gastroenteritis is common in patients receiving allogeneic hematopoietic stem cell transplantation and it is difficult to distinguish from acute graft-versus-host disease (aGvHD), which has very similar symptoms but needs quite different treatment. CMV gastroenteritis is caused by local infection or reactivation of CMV in the gastrointestinal tract while aGvHD is due to immune rejection. The gold standard of diagnosis of CMV gastroenteritis and aGvHD is gastrointestinal biopsy under endoscopy, which is invasive and can potentially lead to severe side effects. Stool samples testing with quantitative polymerase chain reaction (qPCR) may be an alternative, while the application in trace level measurements and precision are not all satisfactory enough in reported research.<br><br>METHODS: In this study, we designed a novel method that extracted the cell free DNA (cfDNA) from the fecal supernatant to perform digital PCR (dPCR) for the detection of CMV, analyzed the performance and compared it with the total DNA extracted by the current procedure.<br><br>RESULTS: Twenty-two paired stool samples using two DNA extraction methods proved that the cfDNA extraction method had markedly higher DNA concentrations and control gene copy number, suggesting that cfDNA may be more informative and more useful for the detection of CMV DNA segment. The dPCR approach in detecting CMV DNA segment also exhibit good linearity (R[2]&#x2009;=&#x2009;0.997) and higher sensitivity (limit of detection at 50% was 3.534&#xa0;copies/&#x3bc;L). Eighty-two stool samples from 44 immunocompromised patients were analyzed, CMV-positive rate was 28%, indicating that more than one-quarter of the gastrointestinal symptoms within these patients may be caused by CMV infection or reactivation.<br><br>CONCLUSION: The combined results suggest that detection of CMV by dPCR in cfDNA of stool supernatant is a powerful method to identify CMV gastroenteritis and helps in clinical treatment decision making.}, }
@article {pmid36367776, year = {2023}, author = {Zhou, Y and Medik, YB and Patel, B and Zamler, DB and Chen, S and Chapman, T and Schneider, S and Park, EM and Babcock, RL and Chrisikos, TT and Kahn, LM and Dyevoich, AM and Pineda, JE and Wong, MC and Mishra, AK and Cass, SH and Cogdill, AP and Johnson, DH and Johnson, SB and Wani, K and Ledesma, DA and Hudgens, CW and Wang, J and Wadud Khan, MA and Peterson, CB and Joon, AY and Peng, W and Li, HS and Arora, R and Tang, X and Raso, MG and Zhang, X and Foo, WC and Tetzlaff, MT and Diehl, GE and Clise-Dwyer, K and Whitley, EM and Gubin, MM and Allison, JP and Hwu, P and Ajami, NJ and Diab, A and Wargo, JA and Watowich, SS}, title = {Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration.}, journal = {The Journal of experimental medicine}, volume = {220}, number = {2}, pages = {}, pmid = {36367776}, issn = {1540-9538}, support = {R01 AI109294/AI/NIAID NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI133822/AI/NIAID NIH HHS/United States ; R56 AI109294/AI/NIAID NIH HHS/United States ; R01 HL158796/HL/NHLBI NIH HHS/United States ; P50 CA221703/CA/NCI NIH HHS/United States ; R01 CA187076/CA/NCI NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Interleukin-6 ; Quality of Life ; *Colitis/pathology ; Immunotherapy ; Inflammation ; }, abstract = {Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-CTLA-4 (αCTLA-4)-mediated toxicity upon disruption of gut homeostatic immunity. We found αCTLA-4 drove increased inflammation and colonic tissue damage in mice with genetic predisposition to intestinal inflammation, acute gastrointestinal infection, transplantation with a dysbiotic fecal microbiome, or dextran sodium sulfate administration. We identified an immune signature of αCTLA-4-mediated irAEs, including colonic neutrophil accumulation and systemic interleukin-6 (IL-6) release. IL-6 blockade combined with antibiotic treatment reduced intestinal damage and improved αCTLA-4 therapeutic efficacy in inflammation-prone mice. Intestinal immune signatures were validated in biopsies from patients with ICB colitis. Our work provides new preclinical models of αCTLA-4 intestinal irAEs, mechanistic insights into irAE development, and potential approaches to enhance ICB efficacy while mitigating irAEs.}, }
@article {pmid36363516, year = {2022}, author = {Abenavoli, L and Maurizi, V and Rinninella, E and Tack, J and Di Berardino, A and Santori, P and Rasetti, C and Procopio, AC and Boccuto, L and Scarpellini, E}, title = {Fecal Microbiota Transplantation in NAFLD Treatment.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {11}, pages = {}, pmid = {36363516}, issn = {1648-9144}, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/complications ; Fecal Microbiota Transplantation ; *Carcinoma, Hepatocellular ; Ecosystem ; *Liver Neoplasms ; Dysbiosis/therapy/complications ; Bile Acids and Salts ; }, abstract = {Introduction: Gut microbiota is not only a taxonomic biologic ecosystem but is also involved in human intestinal and extra-intestinal functions such as immune system modulation, nutrient absorption and digestion, as well as metabolism regulation. The latter is strictly linked to non-alcoholic fatty liver disease (NAFLD) pathophysiology. Materials and methods: We reviewed the literature on the definition of gut microbiota, the concepts of "dysbiosis" and "eubiosis", their role in NAFLD pathogenesis, and the data on fecal microbiota transplantation (FMT) in these patients. We consulted the main medical databases using the following keywords, acronyms, and their associations: gut microbiota, eubiosis, dysbiosis, bile acids, NAFLD, and FMT. Results: Gut microbiota qualitative and quantitative composition is different in healthy subjects vs. NALFD patients. This dysbiosis is associated with and involved in NAFLD pathogenesis and evolution to non-acoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). In detail, microbial-driven metabolism of bile acids (BAs) and interaction with hepatic and intestinal farnesoid nuclear X receptor (FXR) have shown a determinant role in liver fat deposition and the development of fibrosis. Over the use of pre- or probiotics, FMT has shown preclinical and initial clinical promising results in NAFLD treatment through re-modulation of microbial dysbiosis. Conclusions: Promising clinical data support a larger investigation of gut microbiota dysbiosis reversion through FMT in NAFLD using randomized clinical trials to design precision-medicine treatments for these patients at different disease stages.}, }
@article {pmid36362265, year = {2022}, author = {Nirmalkar, K and Qureshi, F and Kang, DW and Hahn, J and Adams, JB and Krajmalnik-Brown, R}, title = {Shotgun Metagenomics Study Suggests Alteration in Sulfur Metabolism and Oxidative Stress in Children with Autism and Improvement after Microbiota Transfer Therapy.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362265}, issn = {1422-0067}, support = {GR37996//Finch Therapuetics, MA, USA and Arizona Board of regents/ ; }, mesh = {Child ; Humans ; *Autistic Disorder ; RNA, Ribosomal, 16S/genetics/metabolism ; *Autism Spectrum Disorder/genetics/therapy/metabolism ; *Microbiota ; Metagenomics ; Oxidative Stress ; Sulfur ; }, abstract = {Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these links, microbiome therapies have been proposed to improve gastrointestinal (GI) and ASD symptoms in ASD individuals. Previously, our open-label microbiota transfer therapy (MTT) study provided insight into the changes in the gut microbial community of children with ASD after MTT and showed significant and long-term improvement in ASD and GI symptoms. Using samples from the same study, the objective of this work was to perform a deeper taxonomic and functional analysis applying shotgun metagenomic sequencing. Taxonomic analyses revealed that ASD Baseline had many bacteria at lower relative abundances, and their abundance increased after MTT. The relative abundance of fiber consuming and beneficial microbes including Prevotella (P. dentalis, P. enoeca, P. oris, P. meloninogenica), Bifidobacterium bifidum, and a sulfur reducer Desulfovibrio piger increased after MTT-10wks in children with ASD compared to Baseline (consistent at genus level with the previous 16S rRNA gene study). Metabolic pathway analysis at Baseline compared to typically developing (TD) children found an altered abundance of many functional genes but, after MTT, they became similar to TD or donors. Important functional genes that changed included: genes encoding enzymes involved in folate biosynthesis, sulfur metabolism and oxidative stress. These results show that MTT treatment not only changed the relative abundance of important genes involved in metabolic pathways, but also seemed to bring them to a similar level to the TD controls. However, at a two-year follow-up, the microbiota and microbial genes shifted into a new state, distinct from their levels at Baseline and distinct from the TD group. Our current findings suggest that microbes from MTT lead to initial improvement in the metabolic profile of children with ASD, and major additional changes at two years post-treatment. In the future, larger cohort studies, mechanistic in vitro experiments and metatranscriptomics studies are recommended to better understand the role of these specific microbes, functional gene expression, and metabolites relevant to ASD.}, }
@article {pmid36362056, year = {2022}, author = {Ustianowska, K and Ustianowski, &#x141; and Machaj, F and Gorący, A and Rosik, J and Szostak, B and Szostak, J and Pawlik, A}, title = {The Role of the Human Microbiome in the Pathogenesis of Pain.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362056}, issn = {1422-0067}, mesh = {Female ; Humans ; *Visceral Pain/pathology ; Brain/pathology ; Dysbiosis/pathology ; *Microbiota ; *Gastrointestinal Microbiome/physiology ; *Probiotics ; *Chronic Pain ; }, abstract = {Understanding of the gut microbiome's role in human physiology developed rapidly in recent years. Moreover, any alteration of this microenvironment could lead to a pathophysiological reaction of numerous organs. It results from the bidirectional communication of the gastrointestinal tract with the central nervous system, called the gut-brain axis. The signals in the gut-brain axis are mediated by immunological, hormonal, and neural pathways. However, it is also influenced by microorganisms in the gut. The disturbances in the gut-brain axis are associated with gastrointestinal syndromes, but recently their role in the development of different types of pain was reported. The gut microbiome could be the factor in the central sensitization of chronic pain by regulating microglia, astrocytes, and immune cells. Dysbiosis could lead to incorrect immune responses, resulting in the development of inflammatory pain such as endometriosis. Furthermore, chronic visceral pain, associated with functional gastrointestinal disorders, could result from a disruption in the gut microenvironment. Any alteration in the gut-brain axis could also trigger migraine attacks by affecting cytokine expression. Understanding the gut microbiome's role in pain pathophysiology leads to the development of analgetic therapies targeting microorganisms. Probiotics, FODMAP diet, and fecal microbiota transplantation are reported to be beneficial in treating visceral pain.}, }
@article {pmid36359265, year = {2022}, author = {Almeida, C and Oliveira, R and Baylina, P and Fernandes, R and Teixeira, FG and Barata, P}, title = {Current Trends and Challenges of Fecal Microbiota Transplantation-An Easy Method That Works for All?.}, journal = {Biomedicines}, volume = {10}, number = {11}, pages = {}, pmid = {36359265}, issn = {2227-9059}, abstract = {The gut microbiota refers to bacteria lodges in the gastrointestinal tract (GIT) that interact through various complex mechanisms. The disturbance of this ecosystem has been correlated with several diseases, such as neurologic, respiratory, cardiovascular, and metabolic diseases and cancer. Therefore, the modulation of the gut microbiota has emerged as a potential therapeutic tool; of the various forms of gut microbiota modulation, fecal microbiota transplantation (FMT) is the most approached. This recent technique involves introducing fecal material from a healthy donor into the patient's gastrointestinal tract, aiming to restore the gut microbiota and lead to the resolution of symptoms. This procedure implies a careful donor choice, fine collection and handling of fecal material, and a balanced preparation of the recipient and consequent administration of the prepared content. Although FMT is considered a biological therapy with promising effects, side effects such as diarrhea and abdominal pain have also been claimed, making this a significant challenge in the application of FMT. Bearing this in mind, the present review aims to summarize the recent advances in understanding FMT mechanisms, their impact across different pathological conditions, and the associated side effects, emphasizing the most recent published data.}, }
@article {pmid36358736, year = {2022}, author = {He, Y and Huang, J and Li, Q and Xia, W and Zhang, C and Liu, Z and Xiao, J and Yi, Z and Deng, H and Xiao, Z and Hu, J and Li, H and Zu, X and Quan, C and Chen, J}, title = {Gut Microbiota and Tumor Immune Escape: A New Perspective for Improving Tumor Immunotherapy.}, journal = {Cancers}, volume = {14}, number = {21}, pages = {}, pmid = {36358736}, issn = {2072-6694}, support = {81873626, 81902592, 82070785//the National Natural Science Foundation of China/ ; 2020JJ5884//Hunan Natural Science Foundation/ ; 2021RC3027//Hunan Province Young talents Program/ ; }, abstract = {The gut microbiota is a large symbiotic community of anaerobic and facultative aerobic bacteria inhabiting the human intestinal tract, and its activities significantly affect human health. Increasing evidence has suggested that the gut microbiome plays an important role in tumor-related immune regulation. In the tumor microenvironment (TME), the gut microbiome and its metabolites affect the differentiation and function of immune cells regulating the immune evasion of tumors. The gut microbiome can indirectly influence individual responses to various classical tumor immunotherapies, including immune checkpoint inhibitor therapy and adoptive immunotherapy. Microbial regulation through antibiotics, prebiotics, and fecal microbiota transplantation (FMT) optimize the composition of the gut microbiome, improving the efficacy of immunotherapy and bringing a new perspective and hope for tumor treatment.}, }
@article {pmid36357745, year = {2022}, author = {Zhang, YW and Cao, MM and Li, YJ and Zhang, RL and Wu, MT and Yu, Q and Rui, YF}, title = {Fecal microbiota transplantation as a promising treatment option for osteoporosis.}, journal = {Journal of bone and mineral metabolism}, volume = {40}, number = {6}, pages = {874-889}, pmid = {36357745}, issn = {1435-5604}, support = {YL20220525//Winfast Charity Foundation Project/ ; LKZ2022010//Jiangsu Elderly Health Research Project, Key Project of Elderly Health Research Project/ ; }, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Osteoporosis/therapy ; }, abstract = {Osteoporosis is a systemic metabolic bone disease characterized by the descending bone mass and destruction of bone microstructure, which tends to result in the increased bone fragility and associated fractures, as well as high disability rate and mortality. The relation between gut microbiota and bone metabolism has gradually become a research hotspot, and it has been verified that gut microbiota is closely associated with reduction of bone mass and incidence of osteoporosis recently. As a novel "organ transplantation" technique, fecal microbiota transplantation (FMT) mainly refers to the transplantation of gut microbiota from healthy donors to recipients with gut microbiota imbalance, so that the gut microbiota in recipients can be reshaped and play a normal function, and further prevent or treat the diseases related to gut microbiota disorder. Herein, based on the gut-bone axis and proven regulatory effects of gut microbiota on osteoporosis, this review expounds relevant basic researches and clinical practice of FMT on osteoporosis, thus demonstrating the potentials of FMT as a therapeutic option for osteoporosis and further providing certain reference for the future researches.}, }
@article {pmid36356464, year = {2022}, author = {Brandt, A and Baumann, A and Hernández-Arriaga, A and Jung, F and Nier, A and Staltner, R and Rajcic, D and Schmeer, C and Witte, OW and Wessner, B and Franzke, B and Wagner, KH and Camarinha-Silva, A and Bergheim, I}, title = {Impairments of intestinal arginine and NO metabolisms trigger aging-associated intestinal barrier dysfunction and 'inflammaging'.}, journal = {Redox biology}, volume = {58}, number = {}, pages = {102528}, pmid = {36356464}, issn = {2213-2317}, mesh = {Animals ; Mice ; Aging ; Arginase/metabolism ; *Arginine/metabolism ; *Endotoxemia ; *Intestines/metabolism/physiopathology ; *Nitric Oxide/metabolism ; }, abstract = {Aging is considered a state of low grade inflammation, occurring in the absence of any overt infection often referred to as 'inflammaging'. Maintaining intestinal homeostasis may be a target to extend a healthier status in older adults. Here, we report that even in healthy older men low grade bacterial endotoxemia is prevalent. In addition, employing multiple mouse models, we also show that while intestinal microbiota composition changes significantly during aging, fecal microbiota transplantation to old mice does not protect against aging-associated intestinal barrier dysfunction in small intestine. Rather, intestinal NO homeostasis and arginine metabolism mediated through arginase and NO synthesis is altered in small intestine of aging mice. Treatment with the arginase inhibitor norNOHA prevented aging-associated intestinal barrier dysfunction, low grade endotoxemia and delayed the onset of senescence in peripheral tissue e.g., liver. Intestinal arginine and NO metabolisms could be a target in the prevention of aging-associated intestinal barrier dysfunction and subsequently decline and 'inflammaging'.}, }
@article {pmid36355923, year = {2022}, author = {Tang, L and Li, J and Sun, B and Bai, Y and Zhou, X and Chen, L}, title = {Transcriptomic Interaction between Young Fecal Transplantation and Perfluorobutanesulfonate in Aged Zebrafish Gonads.}, journal = {Toxics}, volume = {10}, number = {11}, pages = {}, pmid = {36355923}, issn = {2305-6304}, support = {22006159//National Natural Science Foundation of China/ ; }, abstract = {The transfer of young fecal microbiota has been found to significantly refresh the reproductive endocrine system and effectively ameliorate the toxicity of perfluorobutanesulfonate (PFBS) in aged zebrafish recipients. However, the mechanisms underlying the antagonistic action of young fecal microbiota against the reproductive endocrine toxicity of PFBS remain largely unknown. In this study, the aged zebrafish were transplanted with feces from young donors and then exposed to PFBS for 14 days. After exposure, the shift in the transcriptomic fingerprint of the gonads was profiled by using high-throughput sequencing, aiming to provide mechanistic clues into the interactive mode of action between young fecal transplantation and PFBS's innate toxicity. The results showed that the gene transcription pattern associated with protein and lipid synthesis in the gonads of the aged individuals was quite different from the young counterparts. It was intriguing that the transplantation of young feces established a youth-like transcriptomic phenotype in the elderly recipients, thus attenuating the functional decline and maintaining a healthy aging state of the gonads. A sex specificity response was clearly observed. Compared to the aged females, more metabolic pathways (e.g., glycine, serine, and threonine metabolism; glyoxylate and dicarboxylate metabolism; pyrimidine metabolism) were significantly enriched in aged males receiving young feces transplants. PFBS dramatically altered the transcriptome of aged testes, while a much milder effect was observable in aged ovaries. Accordingly, a suite of biological processes related to germ cell proliferation were disrupted by PFBS in aged males, including the ECM-receptor interaction, retinol metabolism, and folate biosynthesis. In aged ovaries exposed to PFBS, mainly the fatty acid and arginine biosynthesis pathway was significantly affected. However, these transcriptomic disorders caused by PFBS were largely mitigated in aged gonads by transferring young feces. Overall, the present findings highlighted the potential of young fecal transplantation to prevent the functional compromise of gonads resulting from aging and PFBS.}, }
@article {pmid36355135, year = {2022}, author = {Yoshikawa, S and Taniguchi, K and Sawamura, H and Ikeda, Y and Tsuji, A and Matsuda, S}, title = {A New Concept of Associations between Gut Microbiota, Immunity and Central Nervous System for the Innovative Treatment of Neurodegenerative Disorders.}, journal = {Metabolites}, volume = {12}, number = {11}, pages = {}, pmid = {36355135}, issn = {2218-1989}, abstract = {Nerve cell death accounts for various neurodegenerative disorders, in which altered immunity to the integrated central nervous system (CNS) might have destructive consequences. This undesirable immune response often affects the progressive neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, schizophrenia and/or amyotrophic lateral sclerosis (ALS). It has been shown that commensal gut microbiota could influence the brain and/or several machineries of immune function. In other words, neurodegenerative disorders may be connected to the gut-brain-immune correlational system. The engrams in the brain could retain the information of a certain inflammation in the body which might be involved in the pathogenesis of neurodegenerative disorders. Tactics involving the use of probiotics and/or fecal microbiota transplantation (FMT) are now evolving as the most promising and/or valuable for the modification of the gut-brain-immune axis. More deliberation of this concept and the roles of gut microbiota would lead to the development of stupendous treatments for the prevention of, and/or therapeutics for, various intractable diseases including several neurodegenerative disorders.}, }
@article {pmid36355122, year = {2022}, author = {Deda, O and Kachrimanidou, M and Armitage, EG and Mouskeftara, T and Loftus, NJ and Zervos, I and Taitzoglou, I and Gika, H}, title = {Metabolic Phenotyping Study of Mouse Brain Following Microbiome Disruption by C.difficile Colonization.}, journal = {Metabolites}, volume = {12}, number = {11}, pages = {}, pmid = {36355122}, issn = {2218-1989}, support = {This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme &#xab;Human Resources Development, Education and Lifelong Learning&#xbb; in the context of the project "Reinforcement of Postdoctoral Researc//State Scholarships Foundation/ ; }, abstract = {Clostridioides difficile infection (CDI) is responsible for an increasing number of cases of post-antibiotic diarrhea worldwide, which has high severity and mortality among hospitalized elderly patients. The disruption of gut microbiota due to antibacterial medication facilitates the intestinal colonization of C. difficile. In the present study, a murine model was used to investigate the potential effects of antibiotic administration and subsequent colonization by C. difficile, as well as the effects of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the brain metabolome for the first time. Four different metabolomic-based methods (targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS, targeted GC-MS/MS, and untargeted GC-MS) were applied, resulting in the identification of 217 unique metabolites in the brain extracts, mainly glycerophospholipids, glycerolipids, amino acids, carbohydrates, and fatty acids. Univariate and multivariate statistical analysis revealed that CDI, as well as the subsequent treatments, altered significantly several brain metabolites, probably due to gut dysbiosis, and affected the brain through the gut-brain axis. Notably, none of the therapeutic approaches completely restored the brain metabolic profile to the original, healthy, and non-infected phenotype, even after 10 days of treatment.}, }
@article {pmid36353787, year = {2023}, author = {Gweon, TG and Lee, YJ and Yim, SK and Kim, SY and Choi, CH and Cho, YS and , }, title = {Recognition and attitudes of Korean physicians toward fecal microbiota transplantation: a survey study.}, journal = {The Korean journal of internal medicine}, volume = {38}, number = {1}, pages = {48-55}, pmid = {36353787}, issn = {2005-6648}, support = {//Korea Health Industry Development Institute/ ; HI19C0481//Ministry of Health and Welfare/ ; HC20C0099//Ministry of Health and Welfare/ ; 2021R1G1A1094049//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; }, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects/methods ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Surveys and Questionnaires ; Treatment Outcome ; *Physicians ; Republic of Korea ; Recurrence ; }, abstract = {BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) represents a treatment option for recurrent Clostridioides difficile infection (CDI). Recently, FMT has been investigated in various clinical settings other than CDI. This study examined Korean physicians' recognition of FMT and their attitudes toward this procedure.<br><br>METHODS: An online questionnaire included questions on indications for FMT, the FMT process, physicians' attitudes toward FMT for the treatment of CDI and non-CDI diseases, and possible concerns.<br><br>RESULTS: Finally, 107 physicians responded to this survey: 66 (61.7%) had experience of performing FMT, and 86 (80.4%) replied that they were willing to perform FMT for CDI. Two-thirds of physicians (63.6%, n = 68) would perform FMT for recurrent CDI on patients who had at least three recurrences. The most common obstacle to performing FMT for the treatment of CDI was the lack of regulations or guidelines (55.1%, n = 59). Seventy-seven (72.0%) physicians would consider FMT for non- CDI diseases when conventional treatment had failed. The most common obstacle for FMT for the treatment of non-CDI diseases was low treatment efficacy (57.0%, n = 61).<br><br>CONCLUSION: Two-thirds of Korean physicians had experience of performing FMT, and many performed FMT for recurrent CDI. The results of this study will prove useful to researchers and practitioners in FMT in Korea.}, }
@article {pmid36353639, year = {2022}, author = {Li, Y and Ouyang, Y and He, C}, title = {Research trends on clinical fecal microbiota transplantation: A biliometric analysis from 2001 to 2021.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {991788}, pmid = {36353639}, issn = {1664-3224}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects/methods ; *Clostridioides difficile ; Treatment Outcome ; *Clostridium Infections/therapy ; Feces ; }, abstract = {BACKGROUND: Numerous studies on fecal microbiota transplantation (FMT) have been conducted in the past two decades. We aimed to assess the research trends and hotspots in the field of FMT through a quantitative method.<br><br>MATERIALS AND METHODS: The clinical studies of FMT published from 2001 to 2021 were extracted from the Web of Science database. We analyzed the countries, institutions, authors, and keywords of these articles and visually illustrated using VOSviewer and CiteSpace software. The current application of FMT in clinical practice, including indications, efficacy, adverse events, as well as its methodology, such as donor, delivery route, were also evaluated.<br><br>RESULTS: A total of 227 records were finally identified. The number and rate of annual publications increased gradually. The USA ranked highest in the number of publications. Harvard University was the most influential institution, and Digestive Diseases and Sciences was the most productive journal. Kassam Zain published the most papers, and the high-frequency keywords were mainly related to diseases and techniques. Healthy donors were the most widely used donors, and frozen stool had the highest frequency of use. The predominant delivery route was endoscopy followed by oral capsules and enema. FMT was most frequently performed for the treatment of recurrent Clostridium Difficile Infection. The overall efficacy of FMT was 76.88%, and the incidence of minor and severe adverse events were 11.63% and 1.59%, respectively.<br><br>CONCLUSIONS: This study delineated a comprehensive landscape of the advancement in FMT field. Although in its infancy, FMT is a burgeoning option for the treatment of a variety of diseases associated with gut dysbiosis. To improve the efficacy and reduce adverse events, future studies are warranted to optimize the methodology of FMT.}, }
@article {pmid36352460, year = {2022}, author = {Wei, S and Jespersen, ML and Baunwall, SMD and Myers, PN and Smith, EM and Dahlerup, JF and Rasmussen, S and Nielsen, HB and Licht, TR and Bahl, MI and Hvas, CL}, title = {Cross-generational bacterial strain transfer to an infant after fecal microbiota transplantation to a pregnant patient: a case report.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {193}, pmid = {36352460}, issn = {2049-2618}, mesh = {Adult ; Female ; Humans ; Infant, Newborn ; Pregnancy ; Bacteria ; *Clostridioides difficile ; *Clostridium Infections/therapy/microbiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment.<br><br>METHODS: A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults.<br><br>RESULTS: The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient's gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer.<br><br>CONCLUSIONS: The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding. Video Abstract.}, }
@article {pmid36352455, year = {2022}, author = {Liu, Y and Zhao, Y and Qi, J and Ma, X and Qi, X and Wu, D and Xu, Y}, title = {Fecal microbiota transplantation combined with ruxolitinib as a salvage treatment for intestinal steroid-refractory acute GVHD.}, journal = {Experimental hematology &amp; oncology}, volume = {11}, number = {1}, pages = {96}, pmid = {36352455}, issn = {2162-3619}, support = {2021ZKQC03//Translational Research Grant of NCRCH/ ; 2021ZKQC01//Translational Research Grant of NCRCH/ ; 2020ZKPC01//Translational Research Grant of NCRCH/ ; BRA2020398//Jiangsu 333 Project/ ; 81730003//National Natural Science Foundation of China/ ; 82070187//National Natural Science Foundation of China/ ; 2017ZX09304021//National Science and Technology Major Project/ ; 2017YFA0104502//National Key Research and Development Program of China/ ; 2019YFC0840604//National Key Research and Development Program of China/ ; BK20171205//Natural Science Foundation of Jiangsu Province/ ; BE2019655//Social Development Project of Jiangsu Province/ ; }, abstract = {Acute graft-versus-host disease (aGVHD), especially intestinal aGVHD, is one of the most severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) has been applied to the treatment of intestinal steroid-refractory aGVHD (SR-aGVHD). Ruxolitinib is the first drug recommended for SR-aGVHD. Here, we reported the outcome data from 21 patients who had received the combined treatment of FMT with ruxolitinib as a salvage treatment in intestinal SR-aGVHD after HSCT. The overall response rate on day 28 was 71.4% (95% CI 50.4-92.5%), including 10 patients with complete responses. The durable overall response at day 56 in responders was 80%. GVHD relapse rate was 33.3% in responders. The levels of inflammatory cytokines as well as T cells and NK cells activation declined. The diversity of the intestinal microbiota was improved in responders. Viral reactivations and severe cytopenia were the major adverse events (61.9% and 81% respectively). The estimated 6-month overall survival was 57.1% (95% CI: 35.9-78.3%), while event-free survival was 52.4% (95% CI: 21.7%-64.1%). Collectively, FMT with ruxolitinib could be an effective treatment for intestinal SR-aGVHD after HSCT.Trial registration: ClinicalTrials.gov identifier: NCT03148743.}, }
@article {pmid36351614, year = {2022}, author = {Xie, T and Yang, R and Zhang, X and Shen, X and Yu, L and Liao, J and Bao, T and Fang, Q}, title = {Fecal Microbiota Transplantation Alleviated Cerebral Ischemia Reperfusion Injury in Obese Rats.}, journal = {The Tohoku journal of experimental medicine}, volume = {259}, number = {1}, pages = {49-55}, doi = {10.1620/tjem.2022.J094}, pmid = {36351614}, issn = {1349-3329}, mesh = {Animals ; Rats ; Caspase 3/metabolism/pharmacology ; bcl-2-Associated X Protein/metabolism/pharmacology ; Fecal Microbiota Transplantation ; *Neuroprotective Agents/pharmacology ; *Reperfusion Injury/therapy ; Infarction, Middle Cerebral Artery/complications/therapy ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Oxidative Stress ; Apoptosis ; Obesity/complications/therapy ; Body Weight ; Water/pharmacology ; Triglycerides ; Cholesterol ; *Brain Ischemia/complications/therapy ; }, abstract = {This study aimed to investigate whether fecal microbiota transplantation (FMT) provides protection for stroke injury in obese patients. Rats were fed high-fat diet (HFD) for 4 weeks and subjected to middle cerebral artery occlusion (MCAO). After FMT for 30 days, body weight, serum total cholesterol and triglyceride levels, neurological score, brain water content, and cerebral infarction volume were measured. Brain reactive oxygen species, superoxide dismutase and malondialdehyde were detected and the levels of Bcl-2, Bax and cleaved caspase-3 were examined. Rats fed with HFD had higher body weight and higher serum total cholesterol and triglyceride levels. Neurological score was lower, brain water content and cerebral infarction volume were higher in obese rats following MCAO, but FMT improved neurological deficit. Moreover, oxidative stress was enhanced in obese rats following MCAO, but FMT attenuated oxidative stress. Brain Bcl-2 level was lower while Bax and cleaved caspase-3 levels were higher in obese rats following MCAO, but FMT increased brain Bcl-2 level and decreased Bax and cleaved caspase-3 levels. In conclusion, FMT attenuated cerebral ischemic injury in obese rats and the beneficial effects of FMT may be mediated by the attenuation of oxidative stress and apoptosis in the brain.}, }
@article {pmid36348361, year = {2022}, author = {Zhong, Y and Xiao, Y and Gao, J and Zheng, Z and Zhang, Z and Yao, L and Li, D}, title = {Curcumin improves insulin sensitivity in high-fat diet-fed mice through gut microbiota.}, journal = {Nutrition &amp; metabolism}, volume = {19}, number = {1}, pages = {76}, pmid = {36348361}, issn = {1743-7075}, support = {81803221//National Natural Science Foundation of China/ ; 2021JC046//Health Science and Technology Capacity Improvement Project Of Jilin Province/ ; }, abstract = {BACKGROUND: Insulin resistance precedes metabolic syndrome which increases the risk of type 2 diabetes and cardiovascular disease. However, there is a lack of safe and long-lasting methods for the prevention and treatment of insulin resistance. Gut microbiota dysbiosis can lead to insulin resistance and associated glucose and lipid metabolic dysfunction. Thus, the role of gut microbiota in metabolic diseases has garnered growing interest. Curcumin, the active ingredient of tropical plant Curcuma longa, has excellent prospects for the prevention and treatment of metabolic diseases. However, due to the extremely low bioavailability of curcumin, the mechanisms by which curcumin increases insulin sensitivity remains to be elucidated. This study aimed to elucidate the role of gut microbiota in mediating the effects of curcumin on improving insulin sensitivity in high-fat diet (HFD)-fed mice.<br><br>METHODS: Glucose, insulin, and pyruvate tolerance were tested and hepatic triglycerides (TGs) content was measured in HFD-fed mice treated with curcumin (100&#xa0;mg&#xa0;kg[-1] d[-1], p.o.) or vehicle for 4&#xa0;weeks and aforementioned mice after gut microbiota depletion via antibiotic treatment for 4&#xa0;weeks. Fecal microbiota transplantation (FMT) was conducted in endogenous gut microbiota-depleted HFD-fed mice. Glucose and lipid metabolic phenotypes were also measured in recipient mice colonized microbiota from vehicle- or curcumin-treated HFD-fed mice. The mechanisms underlying the effects of curcumin on increasing insulin sensitivity were testified by Western blotting, real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA).<br><br>RESULTS: Curcumin ameliorated HFD-induced glucose intolerance, insulin resistance, pyruvate intolerance, and hepatic TGs accumulation, while these effects were mediated by gut microbiota. Curcumin induced insulin-stimulated Akt phosphorylation levels in insulin-regulated peripheral tissues. The inhibitory effects of curcumin on the expressions of genes involved in hepatic gluconeogenesis and de novo lipogenesis were dependent on gut microbiota. Meanwhile, curcumin upregulated the expression of fibroblast growth factor 15 (FGF15) through gut microbiota.<br><br>CONCLUSIONS: The effects of curcumin on promoting insulin sensitivity were dependent on gut microbiota in HFD-fed mice. Moreover, curcumin at least partly exerted its effects on increasing insulin sensitivity via FGF15 upregulation. This study provided new ideas on nutritional manipulations of gut microbiota for the treatment of metabolic diseases.}, }
@article {pmid36345042, year = {2022}, author = {Zhou, C and Li, J and Guo, C and Zhou, Z and Yang, Z and Zhang, Y and Jiang, J and Cai, Y and Zhou, J and Ming, Y}, title = {Comparison of intestinal flora between patients with chronic and advanced Schistosoma japonicum infection.}, journal = {Parasites &amp; vectors}, volume = {15}, number = {1}, pages = {413}, pmid = {36345042}, issn = {1756-3305}, support = {81771722//National Natural Science Foundation of China/ ; 2021SK2032//Key Research and Development Plan of Hunan Province/ ; }, mesh = {Humans ; Animals ; *Schistosomiasis japonica ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Feces ; Intestines ; *Schistosoma japonicum/genetics ; }, abstract = {BACKGROUND: Schistosoma japonicum infection is an important public health problem, imposing heavy social and economic burdens in 78 countries worldwide. However, the mechanism of transition from chronic to advanced S. japonicum infection remains largely unknown. Evidences suggested that gut microbiota plays a role in the pathogenesis of S. japonicum infection. However, the composition of the gut microbiota in patients with chronic and advanced S. japonicum infection is not well defined. In this study, we compared the composition of the intestinal flora in patients with chronic and advanced S. japonicum infection.<br><br>METHODS: The feces of 24 patients with chronic S. japonicum infection and five patients with advanced S. japonicum infection from the same area were collected according to standard procedures, and 16S rRNA sequencing technology was used to analyze the intestinal microbial composition of the two groups of patients.<br><br>RESULTS: We found that alteration occurs in the gut microbiota between the groups of patients with chronic and advanced S. japonicum infections. Analysis of alpha and beta diversity indicated that the diversity and abundance of intestinal flora in patients with advanced S. japonicum infection were lower than those in patients with chronic S. japonicum infection. Furthermore, Prevotella 9, Subdoligranulum, Ruminococcus torques, Megamonas and Fusicatenibacter seemed to have potential to discriminate different stages of S. japonicum infection and to act as biomarkers for diagnosis. Function prediction analysis revealed that microbiota function in the chronic group was focused on translation and cell growth and death, while that in the advanced group was concentrated on elevating metabolism-related functions.<br><br>CONCLUSIONS: Our study demonstrated that alteration in gut microbiota in different stages of S. japonicum infection plays a potential role in the pathogenesis of transition from chronic to advanced S. japonicum infection. However, further validation in the clinic is needed, and the underlying mechanism requires further study.}, }
@article {pmid36342653, year = {2023}, author = {Orenstein, R}, title = {The Role of Microbiome-Based Therapeutics in Clostridioides difficile Infection: Durable, Long-Term Results of RBX2660.}, journal = {Infectious diseases and therapy}, volume = {12}, number = {1}, pages = {1-7}, pmid = {36342653}, issn = {2193-8229}, abstract = {A recently published manuscript described findings from a phase 2 open label study of the microbiota-based live biotherapeutic product RBX2660 in patients with two or more previous recurrent Clostridioides difficile infection (rCDI) episodes, and described long-term safety and sustained treatment success through 24 months. As previous studies have typically focused on short-term clinical outcomes, these new data provide insight into the tolerability, safety, and efficacy of RBX2660 over the long term. When microbiota-based products were first evaluated, the long-term efficacy and safety were principal concerns of the United States Food and Drug Administration. Microbiota-based live biotherapeutic products (LBPs) represent an emerging approach to the management of CDI and perhaps other gastrointestinal and medical conditions whose pathogenesis is defined by microbial dysbiosis. RBX2660 is a human-derived, broad consortium microbiota-based LBP that consists of a population of microbes obtained from healthy stool donors and may reflect the symbiotic nature of a healthy colonic microbiome. RBX2660 is rectally administered and does not require sedation or special preparation of the recipient. Potential advantages of the rectal administration of RBX2660 include the ease of administration and lack of need for any bowel preparation, which may benefit those who are frail, have swallowing issues, or cannot take bowel laxative preparations. In this multicenter prospective trial of rCDI, patients who achieved treatment success 8 weeks after receiving RBX2660 continued to have a sustained clinical response over the course of long-term follow-up, with more than 90% of treatment responders remaining CDI-free at 6, 12, and 24 months. Following receipt of RBX2660, the gut microbiota of those with treatment success were restored from a dysbiotic state to become more diverse and similar to RBX2660 composition. The restoration of the microbiota occurred as early as 7 days after RBX2660 administration and remained stable through the 24-month analysis. No new adverse outcomes were observed during the prospective assessment, and the safety profile of RBX2660 was consistent with previous studies. Based on the clinical studies, RBX2660 will most likely benefit those with ≥ 1 rCDI episode or those who are at a high risk of subsequent rCDI, such as patients who have comorbid conditions including renal disease, heart disease, or inflammatory bowel disease, or who are immunosuppressed. The role of microbiome-based therapeutics in 47 Clostridioides difficile infection: Durable, long-term results of RBX2660 (MP4 511833 KB).}, }
@article {pmid36341987, year = {2023}, author = {Chen, G and Peng, Y and Huang, Y and Xie, M and Dai, Z and Cai, H and Dong, W and Xu, W and Xie, Z and Chen, D and Fan, X and Zhou, W and Kan, X and Yang, T and Chen, C and Sun, Y and Zeng, X and Liu, Z}, title = {Fluoride induced leaky gut and bloom of Erysipelatoclostridium ramosum mediate the exacerbation of obesity in high-fat-diet fed mice.}, journal = {Journal of advanced research}, volume = {50}, number = {}, pages = {35-54}, pmid = {36341987}, issn = {2090-1224}, mesh = {Firmicutes ; Diet, High-Fat/adverse effects ; Mice ; Animals ; *Fluorides/pharmacology ; *Toll-Like Receptor 4 ; Obesity/prevention &amp; control ; }, abstract = {Fluoride is widely presented in drinking water and foods. A strong relation between fluoride exposure and obesity has been reported. However, the potential mechanisms on fluoride-induced obesity remain unexplored. Objectives and methods The effects of fluoride on the obesity were investigated using mice model. Furthermore, the role of gut homeostasis in exacerbation of the obesity induced by fluoride was evaluated. Results The results showed that fluoride alone did not induce obesity in normal diet (ND) fed mice, whereas, it could trigger exacerbation of obesity in high-fat diet (HFD) fed mice. Fluoride impaired intestinal barrier and activated Toll-like receptor 4 (TLR4) signaling to induce obesity, which was further verified in TLR4[-/-] mice. Furthermore, fluoride could deteriorate the gut microbiota in HFD mice. The fecal microbiota transplantation from fluoride-induced mice was sufficient to induce obesity, while the exacerbation of obesity by fluoride was blocked upon gut microbiota depletion. The fluoride-induced bloom of Erysipelatoclostridium ramosum was responsible for exacerbation of obesity. In addition, a potential strategy for prevention of fluoride-induced obesity was proposed by intervention with polysaccharides from Fuzhuan brick tea. Conclusion Overall, these results provide the first evidence of a comprehensive cross-talk mechanism between fluoride and obesity in HFD fed mice, which is mediated by gut microbiota and intestinal barrier. E. ramosum was identified as a crucial mediator of fluoride induced obesity, which could be explored as potential target for prevention and treatment of obesity with exciting translational value.}, }
@article {pmid36341838, year = {2023}, author = {Dischinger, U and Kötzner, L and Kovatcheva-Datchary, P and Kleinschmidt, H and Haas, C and Perez, J and Presek, C and Koschker, AC and Miras, AD and Hankir, MK and Vogel, J and Germer, CT and Fassnacht, M and Herrmann, MJ and Seyfried, F}, title = {Hypothalamic integrity is necessary for sustained weight loss after bariatric surgery: A prospective, cross-sectional study.}, journal = {Metabolism: clinical and experimental}, volume = {138}, number = {}, pages = {155341}, doi = {10.1016/j.metabol.2022.155341}, pmid = {36341838}, issn = {1532-8600}, mesh = {Humans ; Prospective Studies ; Cross-Sectional Studies ; *Bariatric Surgery ; Weight Loss/physiology ; Obesity/surgery ; Glucagon-Like Peptide 1 ; Hypothalamus ; *Hypothalamic Diseases ; *Gastric Bypass ; }, abstract = {OBJECTIVE: The hypothalamus is the main integrator of peripheral and central signals in the control of energy homeostasis. Its functional relevance for the effectivity of bariatric surgery is not entirely elucidated. Studying the effects of bariatric surgery in patients with hypothalamic damage might provide insight.<br><br>SUMMARY BACKGROUND DATA: Prospective study to analyze the effects of bariatric surgery in patients with hypothalamic obesity (HO) vs. matched patients with common obesity (CO) with and without bariatric surgery.<br><br>METHODS: 65 participants were included (HO-surgery: n&#xa0;=&#xa0;8, HO-control: n&#xa0;=&#xa0;10, CO-surgery: n&#xa0;=&#xa0;12, CO-control: n&#xa0;=&#xa0;12, Lean-control: n&#xa0;=&#xa0;23). Body weight, levels of anorexic hormones, gut microbiota, as well as subjective well-being/health status, eating behavior, and brain activity (via functional MRI) were evaluated.<br><br>RESULTS: Patients with HO lost significantly less weight after bariatric surgery than CO-participants (total body weight loss %: 5.5&#xa0;% vs. 26.2&#xa0;%, p&#xa0;=&#xa0;0.0004). After a mixed meal, satiety and abdominal fullness tended to be lowest in HO-surgery and did not correlate with levels of GLP-1 or PYY. Levels of PYY (11,151&#xa0;&#xb1;&#xa0;1667&#xa0;pmol/l/h vs. 8099&#xa0;&#xb1;&#xa0;1235&#xa0;pmol/l/h, p&#xa0;=&#xa0;0.028) and GLP-1 (20,975&#xa0;&#xb1;&#xa0;2893&#xa0;pmol/l/h vs. 13,060&#xa0;&#xb1;&#xa0;2357&#xa0;pmol/l/h, p&#xa0;=&#xa0;0.009) were significantly higher in the HO-surgery vs. CO-surgery group. Abundance of Enterobacteriaceae and Streptococcus was increased in feces of HO and CO after bariatric surgery. Comparing HO patients with lean-controls revealed an increased activation in insula and cerebellum to viewing high-caloric foods in left insula and cerebellum in fMRI.<br><br>CONCLUSIONS: Hypothalamic integrity is necessary for the effectiveness of bariatric surgery in humans. Peripheral changes after bariatric surgery are not sufficient to induce satiety and long-term weight loss in patients with hypothalamic damage.}, }
@article {pmid36341232, year = {2022}, author = {Tkach, S and Dorofeyev, A and Kuzenko, I and Sulaieva, O and Falalyeyeva, T and Kobyliak, N}, title = {Fecal microbiota transplantation in patients with post-infectious irritable bowel syndrome: A randomized, clinical trial.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {994911}, pmid = {36341232}, issn = {2296-858X}, abstract = {INTRODUCTION: Research in recent years has shown the potential benefits of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS). Acute infectious gastroenteritis is a well-established risk factor for developing such forms of IBS as post-infectious IBS (PI-IBS). However, the effective use of FMT in patients with IP-IBS has not yet been clarified.<br><br>AIM: The study aimed to conduct a single-center, randomized clinical trial (RCT) to assess FMT's safety, clinical and microbiological efficacy in patients with PI-IBS.<br><br>MATERIALS AND METHODS: Patients with PI-IBS were randomized into two groups: I (standard-care, n = 29) were prescribed basic therapy, namely a low FODMAP diet, as well as Otilonium Bromide (1 tablet TID) and a multi-strain probiotic (1 capsule BID) for 1 month; II (FMT group, n = 30), each patient with PI-IBS underwent a single FMT procedure with fresh material by colonoscopy. All patients underwent bacteriological examination of feces for quantitative and qualitative microbiota composition changes. The clinical efficacy of treatment was evaluated according to the dynamics of abdominal symptoms, measured using the IBS-SSS scale, fatigue reduction (FAS scale), and a change in the quality of life (IBS-QoL scale).<br><br>RESULTS: FMT was associated with rapid onset of the effect, manifested in a significant difference between IBS-SSS points after 2 weeks of intervention (p < 0.001). In other time points (after 4 and 12 weeks) IBS-SSS did not differ significantly across both groups. Only after 3 months of treatment did their QoL exceed its initial level, as well value for 2 and 4 weeks, to a significant extent. The change in the ratio of the main microbial phenotypes in the form of an increase in the relative abundance of Firmicutes and Bacteroidetes was recorded in all patients after 4 weeks. It should be noted that these changes were significant but eventually normalized only in the group of PI-IBS patients who underwent FMT. No serious adverse reactions were noted.<br><br>CONCLUSION: This comparative study of the results of FMT use in patients with PI-IBS demonstrated its effectiveness compared to traditional pharmacotherapy, as well as a high degree of safety and good tolerability.}, }
@article {pmid36340300, year = {2022}, author = {Osna, NA and Rasineni, K and Ganesan, M and Donohue, TM and Kharbanda, KK}, title = {Pathogenesis of Alcohol-Associated Liver Disease.}, journal = {Journal of clinical and experimental hepatology}, volume = {12}, number = {6}, pages = {1492-1513}, pmid = {36340300}, issn = {0973-6883}, support = {R01 AA026723/AA/NIAAA NIH HHS/United States ; R01 AA027189/AA/NIAAA NIH HHS/United States ; R01 AA028504/AA/NIAAA NIH HHS/United States ; }, abstract = {Excessive alcohol consumption is a global healthcare problem with enormous social, economic, and clinical consequences. While chronic, heavy alcohol consumption causes structural damage and/or disrupts normal organ function in virtually every tissue of the body, the liver sustains the greatest damage. This is primarily because the liver is the first to see alcohol absorbed from the gastrointestinal tract via the portal circulation and second, because the liver is the principal site of ethanol metabolism. Alcohol-induced damage remains one of the most prevalent disorders of the liver and a leading cause of death or transplantation from liver disease. Despite extensive research on the pathophysiology of this disease, there are still no targeted therapies available. Given the multifactorial mechanisms for alcohol-associated liver disease pathogenesis, it is conceivable that a multitherapeutic regimen is needed to treat different stages in the spectrum of this disease.}, }
@article {pmid36339629, year = {2022}, author = {Ma, C and Yuan, D and Renaud, SJ and Zhou, T and Yang, F and Liou, Y and Qiu, X and Zhou, L and Guo, Y}, title = {Chaihu-shugan-san alleviates depression-like behavior in mice exposed to chronic unpredictable stress by altering the gut microbiota and levels of the bile acids hyocholic acid and 7-ketoDCA.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {1040591}, pmid = {36339629}, issn = {1663-9812}, abstract = {Chaihu-Shugan-San (CSS) is a traditional botanical drug formula often prescribed to treat depression in oriental countries, but its pharmacotherapeutic mechanism remains unknown. It was recently reported that CSS alters the composition of intestinal microflora and related metabolites such as bile acids (BAs). Since the intestinal microflora affects physiological functions of the brain through the gut-microbiota-brain axis, herein we investigated whether CSS altered BA levels, gut microflora, and depression-like symptoms in chronic unpredictable mild stress (CUMS) mice, a well-established mouse model of depression. Furthermore, we determined whether BA manipulation and fecal microbiota transplantation altered CSS antidepressant actions. We found that the BA chelator cholestyramine impaired the antidepressant effects of CSS, which was partially rescued by dietary cholic acid. CSS increased the relative abundance of Parabacteroides distasonis in the colon of CUMS mice, and increased serum levels of various BAs including hyocholic acid (HCA) and 7-ketodeoxycholic acid (7-ketoDCA). Furthermore, gut bacteria transplantation from CSS-treated mice into untreated or cholestyramine-treated CUMS mice restored serum levels of HCA and 7-ketoDCA, alleviating depression-like symptoms. In the hippocampus, CSS-treated mice had decreased expression of genes associated with BA transport (Bsep and Fxr) and increased expression of brain-derived neurotrophic factor and its receptor, TrkB. Overall, CSS increases intestinal P. distasonis abundance, leading to elevated levels of secondary BAs in the circulation and altered expression of hippocampal genes implicated in BA transport and neurotrophic signaling. Our data strongly suggest that the gut microbiota-brain axis contributes to the potent antidepressant action of CSS by modulating BA metabolism.}, }
@article {pmid36339448, year = {2022}, author = {Cheng, Z and Zhang, L and Yang, L and Chu, H}, title = {The critical role of gut microbiota in obesity.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {1025706}, pmid = {36339448}, issn = {1664-2392}, mesh = {Humans ; *Gastrointestinal Microbiome ; Obesity/metabolism ; Prebiotics ; Fecal Microbiota Transplantation/adverse effects ; Inflammation/complications ; }, abstract = {Obesity is a global epidemic characterized by energy disequilibrium, metabolic disorder, fat mass development, and chronic low-grade inflammation, which significantly affects the health state of individuals of all ages and strains the socioeconomic system. The prevalence of obesity is rising at alarming rates and its etiology involves complicated interplay of diet, genetic, and environmental factors. The gut microbiota, as an important constituent of environmental factors, has been confirmed to correlate with the onset and progression of obesity. However, the specific relationship between obesity and the gut microbiota, and its associated mechanisms, have not been fully elucidated. In this review, we have summarized that the microbial diversity was significantly decreased and the Firmicutes/Bacteroidetes ratio was significantly increased in obesity. The altered gut microbiota and associated metabolites contributed to the progression of the disease by disrupting energy homeostasis, promoting lipid synthesis and storage, modulating central appetite and feeding behavior, as well as triggering chronic inflammation, and that the intentional manipulation of gut microbiota held promise as novel therapies for obesity, including probiotics, prebiotics, and fecal microbiota transplantation.}, }
@article {pmid36339093, year = {2022}, author = {Goldsmith, R and Aburahma, A and Pachhain, S and Choudhury, SR and Phuntumart, V and Larsen, R and Ward, CS and Sprague, JE}, title = {Reversal of temperature responses to methylone mediated through bi-directional fecal microbiota transplantation between hyperthermic tolerant and naïve rats.}, journal = {Temperature (Austin, Tex.)}, volume = {9}, number = {4}, pages = {318-330}, pmid = {36339093}, issn = {2332-8940}, abstract = {The synthetic cathinone ("bath salt") methylone induces a hyperthermia response and with chronic administration tolerance to this hyperthermia has been reported. The microbiome-gut-brain axis has been implicated in multiple bodily systems and pathologies, and intentional manipulation of the gut-microbiome has yielded clinically significant results. Here, we examined the effects of bi-directional Fecal Microbiota Transplantation (FMT) between methylone-induced hyperthermic tolerant (MHT) and methylone-naïve (MN) rats. Rats treated with methylone once per week developed tolerance to methylone-induced hyperthermia by the fourth week. Once tolerant, daily bi-directional FMT between the two groups were performed for seven days prior to the next methylone treatment. The FMT abated the developed tolerance in the MHT group. When treated with methylone for the first time following FMT, recipient MN rats displayed significant tolerance to hyperthermia despite it being their initial drug treatment. Post-FMT, MHT rats displayed elevations in norepinephrine and expression of UCP1, UCP3 and TGR5 in brown adipose tissue, with reductions in expression of TGR5 and UCP3 in skeletal muscle. The pre- and post-FMT methylone tolerance phenotypes of transplant recipients are concurrent with changes in the relative abundance of several classes of Proteobacteria, most evident for Gammaproteobacteria and Alphaproteobacteria. MHT recipients demonstrated a marked increase in the relative proportion of the Firmicutes class Erysipelotrichia. These findings suggest that transplantation of gut-microbiomes can confer phenotypic responses to a drug and that the microbiome may be playing a major role in sympathomimetic-mediated hyperthermia. Abbreviations: 3,4-methylenedioxymethamphetamine (MDMA); methylone-induced hyperthermic tolerant (MHT); methylone-naïve (MN); fecal microbiota transplantation (FMT); uncoupling protein (UCP); subcutaneous (sc); intraperitoneal (ip); brown adipose tissue (BAT); skeletal muscle (SKM); sympathetic nervous system (SNS); norepinephrine (NE); quantitative PCR (qRT-PCR); quantification cycle (Cq); High Performance Liquid Chromatography-Electrochemical Detection (HPLC-EC); amplicon sequence variants (ASVs); principal coordinates analysis (PCoA); permutational multivariate analysis (PERMANOVA).}, }
@article {pmid36338232, year = {2022}, author = {Zheng, L}, title = {New insights into the interplay between intestinal flora and bile acids in inflammatory bowel disease.}, journal = {World journal of clinical cases}, volume = {10}, number = {30}, pages = {10823-10839}, pmid = {36338232}, issn = {2307-8960}, abstract = {Intestinal flora plays a key role in nutrient absorption, metabolism and immune defense, and is considered to be the cornerstone of maintaining the health of human hosts. Bile acids synthesized in the liver can not only promote the absorption of fat-soluble substances in the intestine, but also directly or indirectly affect the structure and function of intestinal flora. Under the action of intestinal flora, bile acids can be converted into secondary bile acids, which can be reabsorbed back to the liver through the enterohepatic circulation. The complex dialogue mechanism between intestinal flora and bile acids is involved in the development of intestinal inflammation such as inflammatory bowel disease (IBD). In this review, the effects of intestinal flora, bile acids and their interactions on IBD and the progress of treatment were reviewed.}, }
@article {pmid36338055, year = {2022}, author = {Yang, Z and Fu, H and Su, H and Cai, X and Wang, Y and Hong, Y and Hu, J and Xie, Z and Wang, X}, title = {Multi-omics analyses reveal the specific changes in gut metagenome and serum metabolome of patients with polycystic ovary syndrome.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1017147}, pmid = {36338055}, issn = {1664-302X}, abstract = {OBJECTIVE: The purpose of this study was to investigate the specific alterations in gut microbiome and serum metabolome and their interactions in patients with polycystic ovary syndrome (PCOS).<br><br>METHODS: The stool samples from 32 PCOS patients and 18 healthy controls underwent the intestinal microbiome analysis using shotgun metagenomics sequencing approach. Serum metabolome was analyzed by ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. An integrative network by combining metagenomics and metabolomics datasets was constructed to explore the possible interactions between gut microbiota and circulating metabolites in PCOS, which was further assessed by fecal microbiota transplantation (FMT) in a rat trial.<br><br>RESULTS: Fecal metagenomics identified 64 microbial strains significantly differing between PCOS and healthy subjects, half of which were enriched in patients. These changed species showed an ability to perturb host metabolic homeostasis (including insulin resistance and fatty acid metabolism) and inflammatory levels (such as PI3K/Akt/mTOR signaling pathways) by expressing sterol regulatory element-binding transcription factor-1, serine/threonine-protein kinase mTOR, and 3-oxoacyl-[acyl-cattier-protein] synthase III, possibly suggesting the potential mechanisms of gut microbiota underlying PCOS. By integrating multi-omics datasets, the panel comprising seven strains (Achromobacter xylosoxidans, Pseudomonas sp. M1, Aquitalea pelogenes, Porphyrobacter sp. HL-46, Vibrio fortis, Leisingera sp. ANG-Vp, and Sinorhizobium meliloti) and three metabolites [ganglioside GM3 (d18:0/16:0), ceramide (d16:2/22:0), and 3Z,6Z,9Z-pentacosatriene] showed the highest predictivity of PCOS (AUC: 1.0) with sensitivity of 0.97 and specificity of 1.0. Moreover, the intestinal microbiome modifications by FMT were demonstrated to regulate PCOS phenotypes including metabolic variables and reproductive hormones.<br><br>CONCLUSION: Our findings revealed key microbial and metabolite features and their interactions underlying PCOS by integrating multi-omics approaches, which may provide novel insights into discovering clinical diagnostic biomarkers and developing efficient therapeutic strategies for PCOS.}, }
@article {pmid36336379, year = {2022}, author = {Aira, A and Rubio, E and Fehér, C and González-Suárez, B and Casals-Pascual, C and Soriano, &#xc1;}, title = {Stool donor recruitment - A one-year experience.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {40}, number = {9}, pages = {495-498}, doi = {10.1016/j.eimce.2021.01.010}, pmid = {36336379}, issn = {2529-993X}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Clostridium Infections ; Feces ; Tissue Donors ; *Microbiota ; }, abstract = {Stool donors for fecal microbiota transference (FMT) should be rigorously screened to identify any disorder in health status. The success of our screening protocol to identify eligible donors in the last year and a half was evaluated and compared with the published literature. The target population was medical students who responded to 3 public calls to donate stools. Qualified donors brought stool samples to our lab. Out of the 110 students who responded to the call, 26 were enrolled as study donors and delivered at least one stool sample. The main reason for volunteer exclusion was body mass index (BMI) <18.5kg/m[2] or >25kg/m[2] (n=11) and for the identification of ESBL Escherichia coli in feces (n=3). Our success rate after the screening protocol was considered high. Understanding the incentives to participate is critical to the success of recruitment strategies as FMT is still a little-known practice for general population.}, }
@article {pmid36329546, year = {2022}, author = {Terry, SM and Barnett, JA and Gibson, DL}, title = {A critical analysis of eating disorders and the gut microbiome.}, journal = {Journal of eating disorders}, volume = {10}, number = {1}, pages = {154}, pmid = {36329546}, issn = {2050-2974}, abstract = {The gut microbiota, also known as our "second brain" is an exciting frontier of research across a multitude of health domains. Gut microbes have been implicated in feeding behaviour and obesity, as well as mental health disorders including anxiety and depression, however their role in the development and maintenance of eating disorders (EDs) has only recently been considered. EDs are complex mental health conditions, shaped by a complicated interplay of factors. Perhaps due to an incomplete understanding of the etiology of EDs, treatment remains inadequate with affected individuals likely to face many relapses. The gut microbiota may be a missing piece in understanding the etiology of eating disorders, however more robust scientific inquiry is needed in the field before concrete conclusions can be made. In this spotlight paper, we critically evaluate what is known about the bi-directional relationship between gut microbes and biological processes that are implicated in the development and maintenance of EDs, including physiological functioning, hormones, neurotransmitters, the central nervous system, and the immune system. We outline limitations of current research, propose concrete steps to move the field forward and, hypothesize potential clinical implications of this research. Our gut is inhabited by millions of bacteria which have more recently been referred to as "our second brain". In fact, these microbes are thought to play a role in ED behaviour, associated anxiety and depression, and even affect our weight. Recent research has dove into this field with promising findings that have the potential to be applied clinically to improve ED recovery. The present paper discusses what is known about the gut microbiome in relation to EDs and the promising implications that leveraging this knowledge, through fecal microbiome transplants, probiotics, and microbiome-directed supplemental foods, could have on ED treatment.}, }
@article {pmid36328641, year = {2022}, author = {Rimawi, RH and Busby, S and Greene, WR}, title = {Severe Clostridioides difficile Infection in the Intensive Care Unit-Medical and Surgical Management.}, journal = {Infectious disease clinics of North America}, volume = {36}, number = {4}, pages = {889-895}, doi = {10.1016/j.idc.2022.07.006}, pmid = {36328641}, issn = {1557-9824}, mesh = {Humans ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy ; Fidaxomicin ; Intensive Care Units ; }, abstract = {Clostridioides difficile remains a major cause of morbidity and mortality in the intensive care unit, and therefore, C difficile guidelines are frequently being updated. Currently, fidaxomicin is the suggested treatment of initial and recurrent infection. Oral vancomycin is an acceptable alternative, followed by rifaximin and fecal microbiota transplantation. Bezlotoxumab is suggested in recurrent cases within 6 months. If patients fail to improve within 3 to 5 days of therapy, especially in patients who have had nasogastric tubes or emergent surgery, fulminant colitis is possible and surgical consultation should be considered for total colectomy.}, }
@article {pmid36326575, year = {2023}, author = {Hu, L and Zhao, Y and Liu, S and Zhang, J and Yuan, H and Xu, H}, title = {High-fat diet in mice led to increased severity of spermatogenesis impairment by lead exposure: perspective from gut microbiota and the efficacy of probiotics.}, journal = {Journal of the science of food and agriculture}, volume = {103}, number = {5}, pages = {2653-2663}, doi = {10.1002/jsfa.12309}, pmid = {36326575}, issn = {1097-0010}, support = {82060606//National Natural Science Foundation of China/ ; }, mesh = {Male ; Mice ; Animals ; Diet, High-Fat ; *Gastrointestinal Microbiome ; Obesity/metabolism ; Lead ; Dysbiosis/metabolism ; Semen/metabolism ; *Probiotics ; *Microbiota ; Spermatogenesis ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: The mechanism of multifactorial spermatogenesis impairment is unclear. This study aimed to investigate the reproductive toxicity of lead (Pb) in mice fed a high-fat diet (HFD) and to delineate the important role of gut microbiota.<br><br>RESULTS: Results showed that, compared with mice fed a normal diet (ND), Pb exposure caused more severe spermatogenesis impairment in HFD-fed mice, including decreased sperm count and motility, seminiferous tubule injury, serum and intratesticular testosterone decline, and downregulated expression level of spermatogenesis-related genes. Besides, 16S sequencing indicated that HFD-fed mice had increased severity of gut microbiota dysbiosis by Pb exposure compared to ND-fed mice. With fecal microbiota transplantation, the same trend of spermatogenesis impairment occurred in recipient mice, which confirmed the important role of gut microbiota. Moreover, probiotics supplementation restored the gut microbial ecosystem, and thus improved spermatogenic function.<br><br>CONCLUSION: Our work suggested that a population with HFD might face more reproductive health risks upon Pb exposure, and revealed an intimate linkage between microbiota dysbiosis and spermatogenesis impairment, accompanied by the potential usefulness of probiotics as prophylactic and therapeutic. &#xa9; 2022 Society of Chemical Industry.}, }
@article {pmid36326009, year = {2022}, author = {Gu, Y and Qin, X and Zhou, G and Wang, C and Mu, C and Liu, X and Zhong, W and Xu, X and Wang, B and Jiang, K and Liu, J and Cao, H}, title = {Lactobacillus rhamnosus GG supernatant promotes intestinal mucin production through regulating 5-HT4R and gut microbiota.}, journal = {Food &amp; function}, volume = {13}, number = {23}, pages = {12144-12155}, doi = {10.1039/d2fo01900k}, pmid = {36326009}, issn = {2042-650X}, mesh = {Mice ; Animals ; *Lacticaseibacillus rhamnosus/metabolism ; *Gastrointestinal Microbiome ; Mucins/metabolism ; Intestinal Mucosa/metabolism ; Mice, Inbred C57BL ; Mucin-2/genetics/metabolism ; *Probiotics/therapeutic use ; *Intestinal Diseases/metabolism ; Constipation ; }, abstract = {Lactobacillus rhamnosus GG (LGG) is a well-known probiotic widely used in foods and drugs. It has been reported that LGG can improve bowel dysfunction in gastrointestinal motility disorders, such as constipation; however, the specific mechanisms remain unclear. The colonic mucus layer is mainly composed of mucin secreted by goblet cells, which plays important roles in lubricating colonic contents and maintaining normal defecation function. It has been reported that increased mucin production is beneficial for relieving constipation symptoms. In this study, we aimed to investigate the role of LGG in regulating intestinal mucin production and the associated mechanisms. Six-week-old C57BL/6J mice were randomized into 3 groups, and were treated with De-Man Rogosa and Sharpe broth (MRS group), tegaserod maleate (tegaserod group) and LGG supernatant (LGGs group) by gavage, respectively. After treatments, defecation parameters, intestinal mucin-2 (MUC2) and serotonin 4 receptor (5-HT4R), goblet cells, and microbiota composition of the mice in each group were assessed. In comparison with the MRS group, higher fecal water content and increased fecal pellet number were found in the tegaserod group and LGGs group. Moreover, LGGs increased the number of goblet cells and upregulated the expression of 5-HT4R and MUC2 in the mouse colon. In addition, Alcian Blue Periodic acid Schiff staining showed that activated 5-HT4R enhanced intestinal MUC2 secretion. Further exploration of the mechanism discovered that LGGs upregulated intestinal S100A10, which was found to be involved in regulating 5-HT4R expression. Furthermore, gut microbiota analysis showed the higher abundance of Alistipes, Allobaculum, Desulfovibrio, and Clostridium XlVa in the LGGs group, which have been reported to be involved in regulating gut motility and the intestinal barrier, and alleviating bowel dysfunction. Interestingly, gut dysbiosis was present in the tegaserod group. It is noteworthy that the fecal microbiota transplanted from LGGs-treated mice significantly improved the gut dysmotility in a constipation mouse model. Our results suggested that LGGs could upregulate 5-HT4R to promote MUC2 production, as well as modulate the gut microbiota, thus improving the defecation function in mice. This finding might provide evidence for the application of diet supplementary LGG in relieving gastrointestinal motility disorders.}, }
@article {pmid36325000, year = {2022}, author = {Favero, C and Ortiz, A and Sanchez-Niño, MD}, title = {Probiotics for kidney disease.}, journal = {Clinical kidney journal}, volume = {15}, number = {11}, pages = {1981-1986}, pmid = {36325000}, issn = {2048-8505}, abstract = {Diet has long been known to influence the course of chronic kidney disease (CKD) and may even result in acute kidney injury (AKI). Diet may influence kidney disease through a direct impact of specific nutrients on the human body through modulation of the gut microbiota composition or through metabolites generated by the gut microbiota from ingested nutrients. The potential for interaction between diet, microbiota and CKD has fueled research into interventions aimed at modifying the microbiota to treat CKD. These interventions may include diet, probiotics, prebiotics, fecal microbiota transplant and other interventions that modulate the microbiota and its metabolome. A recent report identified Lactobacillus casei Zhang from traditional Chinese koumiss as a probiotic that may protect mice from AKI and CKD and slow CKD progression in humans. Potential mechanisms of action include modulation of the gut microbiota and increased availability of short-chain fatty acids with anti-inflammatory properties and of nicotinamide. However, the clinical relevance needs validation in large well-designed clinical trials.}, }
@article {pmid36324251, year = {2023}, author = {Bogatic, D and Bryant, RV and Lynch, KD and Costello, SP}, title = {Systematic review: microbial manipulation as therapy for primary sclerosing cholangitis.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {57}, number = {1}, pages = {23-36}, pmid = {36324251}, issn = {1365-2036}, mesh = {Humans ; *Cholangitis, Sclerosing/therapy ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link between PSC and gastrointestinal microbial dysbiosis has been suggested.<br><br>AIM: To evaluate all potential medical therapies which may exert their effect in PSC by modulation of the gut-liver axis.<br><br>METHODS: We conducted a&#xa0;comprehensive scoping review of PubMed and Cochrane Library, including all articles evaluating an intervention aimed at manipulating the gastrointestinal microbiome in PSC.<br><br>RESULTS: A wide range of therapies proposed altering the gastrointestinal microbiome for the treatment of PSC. In particular, these considered antibiotics including vancomycin, metronidazole, rifaximin, minocycline and azithromycin. However, few therapies have been investigated in randomised, placebo-controlled trials. Vancomycin has been the most widely studied antibiotic, with improvement in alkaline phosphatase reported in two randomised controlled trials, but with no data on disease progression. Unlike antibiotics, strategies such as faecal microbiota transplantation and dietary therapy can improve microbial diversity. However, since these have only been tested in small numbers of patients, robust efficacy data are currently lacking.<br><br>CONCLUSIONS: The gut-liver axis is increasingly considered a potential target for the treatment of PSC. However, no therapies have been demonstrated to improve transplant-free survival. Innovative and well-designed clinical trials of microbiome-targeted therapies with long-term follow-up are required for this orphan disease.}, }
@article {pmid36321732, year = {2023}, author = {Liu, LW and Xie, Y and Li, GQ and Zhang, T and Sui, YH and Zhao, ZJ and Zhang, YY and Yang, WB and Geng, XL and Xue, DB and Chen, H and Wang, YW and Lu, TQ and Shang, LR and Li, ZB and Li, L and Sun, B}, title = {Gut microbiota-derived nicotinamide mononucleotide alleviates acute pancreatitis by activating pancreatic SIRT3 signalling.}, journal = {British journal of pharmacology}, volume = {180}, number = {5}, pages = {647-666}, doi = {10.1111/bph.15980}, pmid = {36321732}, issn = {1476-5381}, support = {82270666//National Natural Science Foundation of China/ ; 81800572//National Natural Science Foundation of China/ ; 82070658//National Natural Science Foundation of China/ ; 81871974//National Natural Science Foundation of China/ ; TD2021H001//Natural Science Foundation of Heilongjiang Province/ ; UNPYSCT-2020157//Youth Innovation Talent Training Program of the General Undergraduate Colleges and Universities in Heilongjiang Province/ ; }, mesh = {Mice ; Rats ; Animals ; *Pancreatitis/drug therapy ; Nicotinamide Mononucleotide/pharmacology ; *Sirtuin 3/metabolism ; *Gastrointestinal Microbiome ; NAD/metabolism ; Dysbiosis ; Ceruletide ; Acute Disease ; Inflammation ; }, abstract = {BACKGROUND AND PURPOSE: Gut microbiota dysbiosis induced by acute pancreatitis (AP) exacerbates pancreatic injury and systemic inflammatory responses. The alleviation of gut microbiota dysbiosis through faecal microbiota transplantation (FMT) is considered a potential strategy to reduce tissue damage and inflammation in many clinical disorders. Here, we aim to investigate the effect of gut microbiota and microbiota-derived metabolites on AP and further clarify the mechanisms associated with pancreatic damage and inflammation.<br><br>EXPERIMENTAL APPROACH: AP rat and mouse models were established by administration of caerulein or sodium taurocholate in vivo. Pancreatic acinar cells were exposed to caerulein and lipopolysaccharide in vitro to simulate AP.<br><br>KEY RESULTS: Normobiotic FMT alleviated AP-induced gut microbiota dysbiosis and ameliorated the severity of AP, including mitochondrial dysfunction, oxidative damage and inflammation. Normobiotic FMT induced higher levels of NAD[+] (nicotinamide adenine dinucleotide)-associated metabolites, particularly nicotinamide mononucleotide (NMN). NMN administration mitigated AP-mediated mitochondrial dysfunction, oxidative damage and inflammation by increasing pancreatic NAD[+] levels. Similarly, overexpression of the NAD[+] -dependent mitochondrial deacetylase sirtuin 3 (SIRT3) alleviated the severity of AP. Furthermore, SIRT3 deacetylated peroxiredoxin 5 (PRDX5) and enhanced PRDX5 protein expression, thereby promoting its antioxidant and anti-inflammatory activities in AP. Importantly, normobiotic FMT-mediated NMN metabolism induced SIRT3-PRDX5 pathway activation during AP.<br><br>CONCLUSION AND IMPLICATIONS: Gut microbiota-derived NMN alleviates the severity of AP by activating the SIRT3-PRDX5 pathway. Normobiotic FMT could be served as a potential strategy for AP treatment.}, }
@article {pmid36321440, year = {2022}, author = {Losurdo, G and Pricci, M and De Bellis, M and Celiberto, F and Russo, F and Riezzo, G and D'attoma, B and Iannone, A and Rendina, M and Ierardi, E and Di Leo, A}, title = {Effect of metronidazole resistance on Helicobacter pylori eradication regimens.}, journal = {Journal of digestive diseases}, volume = {23}, number = {10}, pages = {561-567}, doi = {10.1111/1751-2980.13142}, pmid = {36321440}, issn = {1751-2980}, mesh = {Humans ; Metronidazole/therapeutic use ; Clarithromycin/pharmacology/therapeutic use ; *Helicobacter pylori/genetics ; Anti-Bacterial Agents/therapeutic use ; Drug Therapy, Combination ; *Helicobacter Infections/drug therapy ; Amoxicillin/therapeutic use ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use ; }, abstract = {OBJECTIVES: Guidelines suggest bismuth-containing quadruple therapy (BQT) or concomitant therapy (CT) as first-line therapy in our geographic area. Both schedules contain metronidazole. We aimed to evaluate the effect of metronidazole resistance to Helicobacter pylori (H. pylori) eradication therapy.<br><br>METHODS: We recruited treatment-na&#xef;ve subjects with H. pylori infection who received either CT or BQT during January 2020 and December 2021. Before therapy, a fecal sample was collected using the THD fecal test device from each patient. H. pylori DNA was extracted and mutations of rdxA and frxA genes and A2143G for metronidazole and clarithromycin resistance were investigated using real-time polymerase chain reaction with a high-resolution melting curve.<br><br>RESULTS: Ninety-six patients were enrolled, including 29 received BQT and 67 received CT. The overall eradication rate was 94.8% (100% for BQT and 92.5% for CT). Metronidazole resistance was found in 18 (18.8%) subjects, while clarithromycin resistance was found in 19 (19.8%). All 18 patients with metronidazole resistance achieved successful eradication (five treated with BQT and 13 with CT). The eradication rate in metronidazole-sensitive strains was 93.6%. Of these, 24 received BQT with 100% success, and 54 had CT with five failures (successful eradication in 90.7%). Two patients with treatment failure were resistant to clarithromycin, and the remaining three were susceptible to both clarithromycin and metronidazole. No statistical significance was observed in the eradication rate between metronidazole-resistant and -sensitive strains (100% vs 93.6%, P&#xa0;=&#xa0;0.58).<br><br>CONCLUSION: Metronidazole resistance does not influence the eradication rate of BQT and CT regimens in our geographical area, even if such results need to confirmed in a larger sample.}, }
@article {pmid36318049, year = {2022}, author = {Wang, J and Chen, J and Li, L and Zhang, H and Pang, D and Ouyang, H and Jin, X and Tang, X}, title = {Clostridium butyricum and Bifidobacterium pseudolongum Attenuate the Development of Cardiac Fibrosis in Mice.}, journal = {Microbiology spectrum}, volume = {10}, number = {6}, pages = {e0252422}, pmid = {36318049}, issn = {2165-0497}, mesh = {Dysbiosis/microbiology ; Butyric Acid ; RNA, Ribosomal, 16S/genetics ; Bifidobacterium ; *Cardiovascular Diseases/drug therapy ; *Clostridium butyricum/genetics/metabolism ; Mice ; *Probiotics/therapeutic use/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Animals ; Fibrosis ; }, abstract = {Cardiac fibrosis is an integral aspect of every form of cardiovascular diseases, which is one of the leading causes of death worldwide. It is urgent to explore new effective drugs and treatments. In this paper, transverse aortic constriction (TAC)-induced cardiac fibrosis was significantly alleviated by a cocktail of antibiotics to clear the intestinal flora, indicating that the gut microbiota was associated with the disease process of cardiac fibrosis. We transplanted feces from sham-operated and TAC-treated mice to mice treated with a cocktail of antibiotics. We found that TAC-treated gut microbiota dysbiosis cannot cause cardiac fibrosis on its own. Interestingly, healthy fecal microbiota transplantation could alleviate cardiac fibrosis, indicating that targeted probiotics and related metabolite intervention may restore a normal microenvironment for the treatment or prevention of cardiac fibrosis. We used 16S rRNA sequencing of fecal samples and discovered that butyric acid-producing bacteria and Bifidobacterium pseudolongum were the dominant bacteria in the group with the lowest degree of cardiac fibrosis. Moreover, we demonstrated that sodium butyrate prevented the development of cardiac fibrosis. The effect of Clostridium butyricum (butyric acid-producing bacteria) was better than that of B. pseudolongum on cardiac fibrosis. Surprisingly, the cocktail of two probiotics had a stronger ability than a single probiotic. In conclusion, therapies targeting the gut microbiota and metabolites such as probiotics present new strategies for treating cardiovascular disease. IMPORTANCE Cardiac fibrosis is a basic process in cardiac remodeling. It is related to almost all types of cardiovascular diseases (CVD) and has become an important global health problem. Basic research and a number of clinical studies have shown that myocardial fibrosis can be prevented and reversed to a certain extent. It is urgent to explore new effective drugs and treatments. We indicated a causal relationship between cardiac fibrosis and gut microbiota. Gut microbiota dysbiosis cannot cause cardiac fibrosis on its own. Interestingly, healthy fecal microbiota transplantation could alleviate cardiac fibrosis. According to our findings, the combined use of butyric acid-producing bacteria and B. pseudolongum can help prevent cardiac fibrosis. Therapies targeting the gut microbiota and metabolites, such as probiotics, represent new strategies for treating cardiovascular disease.}, }
@article {pmid36316361, year = {2022}, author = {Li, Y and Chen, M and Ma, Y and Yang, Y and Cheng, Y and Ma, H and Ren, D and Chen, P}, title = {Regulation of viable/inactivated/lysed probiotic Lactobacillus plantarum H6 on intestinal microbiota and metabolites in hypercholesterolemic mice.}, journal = {NPJ science of food}, volume = {6}, number = {1}, pages = {50}, pmid = {36316361}, issn = {2396-8370}, support = {32172189//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Evidence suggests that probiotic interventions reduce non-communicable diseases (NCDs) risk. However, its therapeutic effect and mechanism are still unclear. To evaluate the hypocholesterolemic effect of Lactobacillus plantarum H6 (L.p H6), a new commercial patent strain capable of preventing hypercholesterolemia, and its mechanism in depth, three states of the strain were prepared, namely, viable (vH6), heat-inactivated (iH6), and ultrasonically-lysed (uH6) bacteria cells. The results showed that v/i/uH6 cells could lower serum and liver blood lipid levels, alleviate liver damage and improve glucose tolerance test (GTT) and insulin tolerance test (ITT) indexes. v/i/uH6 cells improved the gut microbial composition and significantly reduced the Firmicutes to Bacteroidetes ratio (F/B ratio) in feces. In particular, Muribaculaceae may be a potential biomarker for effective cholesterol reduction. Also, the recovery of these biochemical indices and gut microbiome was found following fecal microbiota transplantation (FMT) using stool from vH6 treated mice. The v/i/uH6 cells increased the intestinal flora metabolism of vitamins-cofactors, as well as amino acids, while decreasing the relative content of primary bile acids. The Pearson correlation analysis showed that norank_f__Muribaculaceae and Lactobacillus had a negative correlation with blood lipid levels. Overall, v/i/uH6 cells were effective in improving hypercholesterolemia in mice, and this effect was attributed partly to the regulation of intestinal microbiota and metabolites related to lipid metabolism. Our findings provided a theoretical basis for the industrial development of probiotics and postbiotics and the treatment of cholesterol diseases.}, }
@article {pmid36315335, year = {2023}, author = {Mi, F and Wang, X and Zheng, W and Wang, J and Lin, T and Sun, M and Su, M and Li, H and Ye, H}, title = {Effects of Different Preparation Methods on Microbiota Composition of Fecal Suspension.}, journal = {Molecular biotechnology}, volume = {65}, number = {6}, pages = {871-880}, pmid = {36315335}, issn = {1559-0305}, support = {GF19H030012//Zhejiang Provincial Natural Science Foundation of China/ ; 2019C50100//Science and Technology Project of Ningbo/ ; }, mesh = {Rats ; Animals ; *Saline Solution ; Feces ; Fecal Microbiota Transplantation ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Fecal microbiota transplantation is an emerging disease-modifying therapy. The viability of the microbiome in feces and its successful transfer depends on the preparation of fecal microbiota suspension. However, currently, no standard operation procedure is proposed for fecal suspension preparation. This study aims to compare the effect of different preparation methods on the composition of fecal microbiota composition in the rat. Four methods were used to collect the fecal suspension from fresh rat fecal (Group A), including stirring with normal saline (Group B), stirring with normal saline and then standing (Group C), stirring with normal saline and filtered with gauze (Group D), and stirring with normal saline and centrifuged (Group E). 16S ribosomal RNA gene (16S rDNA) sequencing technology was used to analyze the microbiota diversity and composition of each group of samples. Compared with fresh feces, the bacterial richness of the fecal suspension obtained by the four methods was significantly decreased (P < 0.05). The structural similarity with fresh fecal microbiota from high to low is groups B, D, C, and E. All four methods changed the microbiota structure to varying degrees, thus may affect the effect of FMT. In conclusion, choosing different methods to prepare fecal suspensions may help to better optimize the application of FMT.}, }
@article {pmid36313072, year = {2022}, author = {Sarmiento-Andrade, Y and Suárez, R and Quintero, B and Garrochamba, K and Chapela, SP}, title = {Gut microbiota and obesity: New insights.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {1018212}, pmid = {36313072}, issn = {2296-861X}, abstract = {Obesity is a pathology whose incidence is increasing throughout the world. There are many pathologies associated with obesity. In recent years, the influence of the microbiota on both health and pathological states has been known. There is growing information related to changes in the microbiome and obesity, as well as its associated pathologies. Changes associated with age, exercise, and weight changes have been described. In addition, metabolic changes associated with the microbiota, bariatric surgery, and fecal matter transplantation are described. In this review, we summarize the biology and physiology of microbiota in obese patients, its role in the pathophysiology of several disorders associated, and the emerging therapeutic applications of prebiotics, probiotics, and fecal microbiota transplantation.}, }
@article {pmid36312938, year = {2022}, author = {Cui, X and Chen, J and Yang, Y}, title = {Administration of selenomethionine in combination with serine benefits diabetes via gut microbiota.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1007814}, pmid = {36312938}, issn = {1664-302X}, abstract = {Either selenium or serine could modulate glucose homeostasis, however, whether there are synergistic effects of selenium with serine on diabetes remains to be unknown. In the present study, eight male db/m mice were used as a control, and 24 male diabetic db/db mice were either orally gavaged with PBS, or with selenomethionine alone, or with both selenomethionine and serine, to investigate the effects of selenomethionine and serine on body weight and glucose level. Furthermore, intestinal microbiota composition was analyzed and fecal microbiota transplantation (FMT) was performed to explore whether microbes mediate the beneficial effects of selenomethionine and serine. The results showed that administration of selenomethionine decreased body weight, adipose tissue weight and serum glucose level in db/db diabetic mice. Importantly, administration of selenomethionine in combination with serine exerted better effects than selenomethionine alone did. Furthermore, a combined administration of selenomethionine and serine restored the microbial composition in diabetic mice. Corynebacterium glutamicum, Bifidobacterium pseudolongum, and Aerococcus urinaeequi were significantly decreased, whereas Lactobacillus murinus was increased in mice in the selenomethionine group and selenomethionine in combination with serine group, when compared with those in the db/db group. FMT decreased body weight and glucose level in db/db mice, further indicating that microbes play critical roles in the beneficial effects of selenomethionine and serine. Thus, we concluded that administration of selenomethionine in combination with serine benefits diabetes via gut microbes. Our results suggested that the synergic application of selenomethionine and serine could be potentially used for the treatment of diabetes.}, }
@article {pmid36312936, year = {2022}, author = {Pan, T and Zheng, S and Zheng, W and Shi, C and Ning, K and Zhang, Q and Xie, Y and Xiang, H and Xie, Q}, title = {Christensenella regulated by Huang-Qi-Ling-Hua-San is a key factor by which to improve type 2 diabetes.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1022403}, pmid = {36312936}, issn = {1664-302X}, abstract = {There is a lot of evidence that oral hypoglycemic drugs work by affecting gut microbes, but the key strains responsible for this effect are not well known. Huang-Qi-Ling-Hua-San (HQLHS), composed of Astragalus Membranaceus, Ganoderma lucidum, Inonotus obliquus, and Momordica charantia L., is a specially designed Chinese medicine formula to treat type 2 diabetes (T2D). In this study, a mouse model of T2D induced by high-fat diet and streptozotocin was used to explore the mechanism of HQLHS in improving hyperglycemia and hyperlipidemia through multiple rounds of animal experiments, such as HQLHS feeding, fecal microbiota transplantation (FMT), and live bacteria feeding, so as to explore the potential target intestinal flora in its hypoglycemic effect. Results show that such specific taxa as Bifidobacterium, Turicibacter, Alistipes, Romboutsia, and Christensenella were identified to be preferably enriched by HQLHS and then assumed to be the target microbes. Herein, FMT was used to test if the upregulated beneficial bacteria by HQLHS play a therapeutic role. The strain Christensenella minuta DSM 22607 and the strain Christensenella timonensis DSM 102800 were selected to test the beneficial effect of Christensenella taxa on T2D. Diabetic animals supplemented with these strains showed the improvement in blood glucose and lipid metabolism, the promotion of GLP-1 secretion, the increase in antioxidant capacity, the inhibition of hepatic gluconeogenesis, the suppression of intestinal glucose absorption, the enhancement of intestinal barrier, reduced LPS-induced inflammation, and the reduction of branched amino acids (BCAAs) content in the liver. Overall, these data demonstrate that Christensenella plays a beneficial role in T2D and is a target for the action of HQLHS therapy.}, }
@article {pmid36312920, year = {2022}, author = {Yang, JY and Liu, MJ and Lv, L and Guo, JR and He, KY and Zhang, H and Wang, KK and Cui, CY and Yan, BZ and Du, DD and Wang, JH and Ding, Q and Liu, GL and Xu, ZX and Jian, YP}, title = {Metformin alleviates irradiation-induced intestinal injury by activation of FXR in intestinal epithelia.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {932294}, pmid = {36312920}, issn = {1664-302X}, abstract = {Abdominal irradiation (IR) destroys the intestinal mucosal barrier, leading to severe intestinal infection. There is an urgent need to find safe and effective treatments to reduce IR-induced intestinal injury. In this study, we reported that metformin protected mice from abdominal IR-induced intestinal injury by improving the composition and diversity of intestinal flora. The elimination of intestinal microbiota (Abx) abrogated the protective effects of metformin on irradiated mice. We further characterized that treatment of metformin increased the murine intestinal abundance of Lactobacillus, which mediated the radioprotective effect. The administration of Lactobacillus or fecal microbiota transplantation (FMT) into Abx mice considerably lessened IR-induced intestinal damage and restored the radioprotective function of metformin in Abx mice. In addition, applying the murine intestinal organoid model, we demonstrated that IR inhibited the formation of intestinal organoids, and metformin alone bore no protective effect on organoids after IR. However, a combination of metformin and Lactobacillus or Lactobacillus alone displayed a strong radioprotection on the organoid formation. We demonstrated that metformin/Lactobacillus activated the farnesoid X receptor (FXR) signaling in intestinal epithelial cells and hence upregulated tight junction proteins and mucins in intestinal epithelia, increased the number of goblet cells, and augmented the mucus layer thickness to maintain the integrity of intestinal epithelial barrier, which eventually contributed to reduced radiation intestinal injury. In addition, we found that Lactobacillus abundance was significantly increased in the intestine of patients receiving metformin while undergoing abdominal radiotherapy and the abundance was negatively correlated with the diarrhea duration of patients. In conclusion, our results demonstrate that metformin possesses a protective effect on IR-induced intestinal injury by upregulating the abundance of Lactobacillus in the intestine.}, }
@article {pmid36309938, year = {2022}, author = {Wu, Y and Hang, Z and Lei, T and Du, H}, title = {Intestinal Flora Affect Alzheimer's Disease by Regulating Endogenous Hormones.}, journal = {Neurochemical research}, volume = {47}, number = {12}, pages = {3565-3582}, pmid = {36309938}, issn = {1573-6903}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Alzheimer Disease/metabolism ; Intestines ; Brain/metabolism ; Hormones/metabolism ; }, abstract = {Alzheimer's disease (AD) is a central nervous system disease that can lead to cognitive impairment and progressive memory loss. An increasing number of studies have shown that intestinal flora play a crucial role in regulating the brain-gut axis. Short-chain fatty acids are metabolites of intestinal flora that regulate hormone synthesis and play an essential role in microbial-intestinal-brain communication. An imbalance of intestinal flora can promote microglia to secrete proinflammatory factors, cause nerve inflammation, and then affect cognitive and learning ability. However, the mechanism is not clear. From this, we infer that endogenous hormones may be the medium for intestinal flora to affect the process of AD. This review of the relationships among AD, endogenous hormones, and intestinal flora expounds on the critical role of various hormones in the brain-gut axis. It discusses intervention measures aimed at intestinal flora to prevent or delay AD occurrence. Finally, the potential development prospects of fecal microbiota transplantation in treating AD are put forward, which provide potential ideas for future AD research.}, }
@article {pmid36309716, year = {2022}, author = {Ma, J and Chen, T and Ma, X and Zhang, B and Zhang, J and Xu, L and Wang, Y and Huang, J and Liu, Z and Wang, F and Tang, X}, title = {Comprehensive bibliometric and visualized analysis of research on fecal microbial transplantation published from 2000 to 2021.}, journal = {Biomedical engineering online}, volume = {21}, number = {1}, pages = {78}, pmid = {36309716}, issn = {1475-925X}, support = {82074420//National Natural Science Foundation of China/ ; 81830118//National Natural Science Foundation of China/ ; 2019-QNRC1-02//Young Elite Scientists Sponsorship Program by CAST/ ; CI2021A01012//China Academy of Chinese Medical Sciences Innovation Fund/ ; ZYYCXTD-C-202010//Inheritance and innovation team of Traditional Chinese Medicine for the treatment of Refractory Gastrointestinal Diseases/ ; }, mesh = {*Biomedical Research ; Publications ; Bibliometrics ; China ; }, abstract = {BACKGROUND: Fecal microbial transplantation has emerged in recent years as a method of treating disease by rebuilding the intestinal flora. However, few bibliometric analyses have systematically studied this area of research. We aimed to use bibliometric analysis to visualize trends and topical research in fecal microbial transplantation to help provide insight into future trends in clinical and basic research.<br><br>MATERIALS AND METHODS: Articles and reviews related to fecal microbial transplantation were collected from the Web of Science Core Collection. Significant information associated with this field was visually analyzed by using Biblioshiny and CtieSpace software.<br><br>RESULTS: A total of 3144 articles and overviews were included. The number of publications related to fecal microbial transplantation significantly increased yearly. These publications mainly came from 100 countries, led by the US and China, and 521 institutions. The most prolific and influential author is KHORUTS A. The main disciplines and application fields of fecal microbial transplantation included molecular /biology/immunology and medicine/clinical medicine, and the research foundation of fecal microbial transplantation was molecular /biology/genetics and health/nursing/medicine. An alluvial flow visualization showed several landmark articles. New developments were identified in terms of reference and keyword citation bursts. Data analysis showed that different FMT preparation and delivery methods gradually appeared as research hotspots. The main research keywords in the last 3&#xa0;years were chain fatty acids, Akkermansia muciniphila, and insulin sensitivity, other keywords were current and developing research fields.<br><br>CONCLUSION: Research on fecal microbial transplantation is flourishing and many new applications of fecal microbial transplantation are emerging. Microbial metabolites such as short-chain fatty acids and the microbiota-gut-brain axis have become the focus of current research and are future research trends.}, }
@article {pmid36309224, year = {2022}, author = {Najafi, S and Majidpoor, J and Mortezaee, K}, title = {The impact of microbiota on PD-1/PD-L1 inhibitor therapy outcomes: A focus on solid tumors.}, journal = {Life sciences}, volume = {310}, number = {}, pages = {121138}, doi = {10.1016/j.lfs.2022.121138}, pmid = {36309224}, issn = {1879-0631}, mesh = {Humans ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy/methods ; *Neoplasms/drug therapy ; *Gastrointestinal Microbiome ; }, abstract = {Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in the last decade. Among various checkpoints identified so far, interaction between programmed death-1 (PD-1) with programmed death ligand 1 (PD-L1) and their targeting using human monoclonal antibodies has attracted the most attention and is considered as the most prominent treatment with the best clinical outcomes. Accumulating evidence is the witness for the impact of gut microbiota on clinical responses and ICI efficacy. Specific bacterial species are identified in fecal specimens of cancer patients responding to the anti-PD-(L)1 immunotherapy, while non-responders demonstrate high abundance of other bacterial sources. Thus, the composition of gut microbiota may suggest potential biomarker in identification of patients with the best responses to immunotherapy. Notably, fecal microbial transplantation (FMT) from responders to non-responders has shown hopeful results in improving clinical outcomes and overcoming resistance to ICIs. Additionally, some bacterial components, such as the use of antibiotics and probiotic supplements have been shown to affect the efficacy of ICIs treatment. However, employment of these findings requires further investigations and precise understanding of the impact of gut microbiota on the host's immune responses. In the current review, we aim to discuss the roles of PD-1/PD-L1 checkpoint pathway, their therapeutic significance, and the impact of gut microbiota/products on the PD-1/PD-L1 immunotherapy outcomes.}, }
@article {pmid36309048, year = {2023}, author = {Xu, H and Yang, F and Bao, Z}, title = {Gut microbiota and myocardial fibrosis.}, journal = {European journal of pharmacology}, volume = {940}, number = {}, pages = {175355}, doi = {10.1016/j.ejphar.2022.175355}, pmid = {36309048}, issn = {1879-0712}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis/metabolism ; Ecosystem ; *Probiotics/therapeutic use ; *Cardiomyopathies ; Fibrosis ; }, abstract = {Myocardial fibrosis (MF) is a pathophysiological condition that accompanies various myocardial diseases and comprises a damaged myocardial matrix repair process. Although fibrosis plays a vital role in repair, it ultimately alters cardiac systolic and diastolic functions. The gut microbiota is a complex and dynamic ecosystem with billions of microorganisms that produce bioactive compounds that influence host health and disease progression. Intestinal microbiota has been shown to correlate with cardiovascular disease, and dysbiosis of the intestinal microbiota is involved in the development of MF. In this review, we discuss the role of intestinal microbiota in the process of MF, including alterations in microbiota composition and the effects of metabolites. We also discuss how diet and medicines can affect cardiac fibrosis by influencing the gut microbiota, and potential future therapies targeting the gut-heart axis. A healthy gut microbiota can prevent disease, but dysbiosis can lead to various symptoms, including the induction of heart disease. In this review, we discuss the relevance of the gut-heart axis and the multiple pathways by which gut microbiota may affect cardiac fibrosis, including inflammatory factors, immune cells, and gut microbiota metabolites, such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs). Finally, we discuss the involvement of gut microbiota in the treatment of cardiac fibrosis, including drugs, fecal microbiota transplantation, and oral probiotics or prebiotics. With future studies on the relationship between the heart and gut microbiota, we hope to find better ways to improve MF through the gut-heart axis.}, }
@article {pmid36305395, year = {2022}, author = {Ju, Y and Wang, X and Wang, Y and Li, C and Yue, L and Chen, F}, title = {[Application of metagenomic and culturomic technologies in fecal microbiota transplantation: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {38}, number = {10}, pages = {3594-3605}, doi = {10.13345/j.cjb.220573}, pmid = {36305395}, issn = {1872-2075}, mesh = {Humans ; *Fecal Microbiota Transplantation ; Metagenomics ; Feces/microbiology ; *Gastrointestinal Microbiome ; Bacteria ; }, abstract = {Fecal microbiota transplantation (FMT) refers to using the intestinal microorganisms present in the feces or processed feces from healthy people for treating various types of diseases, such as digestive and metabolic diseases. The rapid development of metagenomic and culturomic technologies in gut microbiome analysis provides powerful tools for the FMT research and its clinical applications. Metagenomics technologies comprehensively revealed the diversity and functions of gut microbiota under health and disease conditions, while culturomics technologies helped isolation and identification of "unculturable" bacteria in the human gut under conventional culture conditions. The combination of these two technologies not only enabled us better understand the FMT regularities of cause and effect in clinical practices, but also effectively promoted its applications. Considering the above advantages, this article summarized the applications of metagenomics and culturomics technologies in FMT and prospected its future development trend.}, }
@article {pmid36304525, year = {2022}, author = {Zou, B and Liu, SX and Li, XS and He, JY and Dong, C and Ruan, ML and Xu, L and Bai, T and Huang, ZH and Shu, SN}, title = {Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {964154}, pmid = {36304525}, issn = {2296-2360}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for intestinal and extra-intestinal disorders. Nonetheless, long-term safety and efficacy remain major challenges for FMT applications. To date, few long-term follow-up studies have been published on FMT in children.<br><br>METHODS: Retrospective reviewed the medical charts of 74 patients who underwent 508 FMT courses between August 2014 and July 2019 at our medical center. All the FMT procedures followed uniform standards. Baseline characteristics pre-FMT and follow-up data were collected at 1, 3, 6, 12, 36, 60, and 84 months after FMT. All potential influencing factors for adverse events (AEs) were analyzed and assessed using regression analyses.<br><br>RESULTS: A total of 70 (13.7%) short-term AEs occurred in twenty-six patients (35.1%). Most AEs (88.5%) occurred within 2 days post-FMT. A total of 91.4% of the AEs were self-limiting. Ulcerative colitis (UC) and within four times of FMT were associated with a higher rate of AEs (p = 0.028 and p = 0.021, respectively). The primary clinical remission rate after FMT was as high as 72.9%. Twenty-five children were followed for more than 5 years after FMT. The clinical remission rates gradually decreased over time after FMT. During follow-up, none of the patients developed autoimmune, metabolic, or rheumatologic disorders or tumor-related diseases. However, nine children developed rhinitis, five developed rhinitis, were underweight, and six developed constipation.<br><br>CONCLUSIONS: FMT is a safe and effective treatment for dysbiosis in children. The long-term efficacy of FMT for each disease decreased over time. Moreover, multiple FMTs are recommended 3 months post-FMT for recurrent diseases.}, }
@article {pmid36302811, year = {2022}, author = {Aalam, SMM and Crasta, DN and Roy, P and Miller, AL and Gamb, SI and Johnson, S and Till, LM and Chen, J and Kashyap, P and Kannan, N}, title = {Genesis of fecal floatation is causally linked to gut microbial colonization in mice.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {18109}, pmid = {36302811}, issn = {2045-2322}, support = {P30 DK084567/DK/NIDDK NIH HHS/United States ; R01 DK114007/DK/NIDDK NIH HHS/United States ; }, mesh = {Mice ; Humans ; Animals ; *Gastrointestinal Microbiome ; Feces/microbiology ; Fecal Microbiota Transplantation ; Metagenomics ; Bacteria/genetics ; }, abstract = {The origin of fecal floatation phenomenon remains poorly understood. Following our serendipitous discovery of differences in buoyancy of feces from germ-free and conventional mice, we characterized microbial and physical properties of feces from germ-free and gut-colonized (conventional and conventionalized) mice. The gut-colonization associated differences were assessed in feces using DNA, bacterial-PCR, scanning electron microscopy, FACS, thermogravimetry and pycnometry. Based on the differences in buoyancy of feces, we developed levô in fimo test (LIFT) to distinguish sinking feces (sinkers) of germ-free mice from floating feces (floaters) of gut-colonized mice. By simultaneous tracking of microbiota densities and gut colonization kinetics in fecal transplanted mice, we provide first direct evidence of causal relationship between gut microbial colonization and fecal floatation. Rare discordance in LIFT and microbiota density indicated that enrichment of gasogenic gut colonizers may be necessary for fecal floatation. Finally, fecal metagenomics analysis of 'floaters' from conventional and syngeneic fecal transplanted mice identified colonization of > 10 gasogenic bacterial species including highly prevalent B. ovatus, an anaerobic commensal bacteria linked with flatulence and intestinal bowel diseases. The findings reported here will improve our understanding of food microbial biotransformation and gut microbial regulators of fecal floatation in human health and disease.}, }
@article {pmid36301100, year = {2022}, author = {Bai, X and Liu, G and Yang, J and Zhu, J and Wang, Q and Zhou, Y and Gu, W and La, L and Li, X}, title = {Changes in the Gut Microbiota of Rats in High-Altitude Hypoxic Environments.}, journal = {Microbiology spectrum}, volume = {10}, number = {6}, pages = {e0162622}, pmid = {36301100}, issn = {2165-0497}, mesh = {Rats ; Male ; Animals ; Altitude ; Rats, Sprague-Dawley ; *Gastrointestinal Microbiome/genetics ; *Altitude Sickness ; RNA, Ribosomal, 16S/genetics ; }, abstract = {This study was conducted to investigate the effects of high-altitude hypoxic environments on the gut microbiota. Male Sprague-Dawley rats were randomly divided into three groups, namely, the plain, moderate-altitude hypoxic, and high-altitude hypoxic groups. On the 3rd, 7th, 15th, and 30th days of exposure, fecal samples were collected and analyzed via 16S rRNA gene sequencing technology. Fecal microbiota transplantation (FMT) experiments were also performed. The results showed significant differences between the gut microbiota structure and diversity of rats in the high-altitude hypoxic group and those of rats in the other groups. Further, compared with that of rats in the plain group, the gut microbiota of rats in the two hypoxic groups showed the most significant changes on day 7. Furthermore, the gut microbiota of the rats in the FMT groups exhibited changes and became increasingly similar to those of the rats in the hypoxic groups. We also identified the phylum Firmicutes, genus Akkermansia, and genus Lactobacillus as the core microbiota under hypoxic conditions. Phenotypic analysis indicated a decrease in the proportion of aerobic bacteria and an increase in that of anaerobic bacteria, possibly owing to the high-altitude hypoxic environment. Additionally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including carbohydrate metabolism, energy metabolism, glycan biosynthesis, and metabolism. These findings indicated significant changes in gut microbiota structure and diversity under high-altitude hypoxia, establishing a foundation for further research on the pathogenesis and development of diseases, as well as drug metabolism, under high-altitude hypoxia. IMPORTANCE In this study, we investigated the effects of high-altitude hypoxic environments with low oxygen levels on the gut microbiota characteristics of rats. We observed that high-altitude hypoxia is an important environmental factor that can affect gut microbiota structure and diversity, thereby affecting homeostasis in the host intestinal environment. These findings provide a basis for further studies on disease initiation and development, as well as drug metabolism, in high-altitude hypoxic environments.}, }
@article {pmid36300959, year = {2022}, author = {Patwa, SA and Ward, C and Kelly, CR}, title = {FMT: What's Next? A Narrative Review of Fecal Microbiota Transplantation in Clostridioides difficile Infection and Inflammatory Bowel Disease.}, journal = {Rhode Island medical journal (2013)}, volume = {105}, number = {9}, pages = {20-24}, pmid = {36300959}, issn = {2327-2228}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile ; Treatment Outcome ; *Clostridium Infections/therapy/complications ; *Inflammatory Bowel Diseases/therapy/complications ; Chronic Disease ; }, abstract = {Fecal microbiota transplantation (FMT) is an increasingly employed treatment option for Clostridioides difficile infection (CDI), with growing data supporting its safety and effectiveness in patients with concurrent inflammatory bowel disease (IBD). Given that alterations in the gut microbiome are associated with both ulcerative colitis (UC) and Crohn's disease (CD), the use of FMT for the treatment of IBD itself is another area of active investigation. In this narrative review, we highlight the evidence for use of FMT in the treatment of CDI in patients with IBD, as well as for IBD alone, and provide insight into the future of microbiome therapeutics.}, }
@article {pmid36300928, year = {2022}, author = {Chen, J and Zeng, P and Gong, L and Zhang, X and Ling, Z and Bi, K and Shi, F and Wang, K and Zhang, Q and Jiang, J and Zhang, Y and Uede, T and El-Omar, EM and Diao, H}, title = {Osteopontin Exacerbates High-Fat Diet-Induced Metabolic Disorders in a Microbiome-Dependent Manner.}, journal = {mBio}, volume = {13}, number = {6}, pages = {e0253122}, pmid = {36300928}, issn = {2150-7511}, mesh = {Animals ; Humans ; Mice ; Diet, High-Fat ; *Gastrointestinal Microbiome ; *Metabolic Diseases ; Mice, Inbred C57BL ; Obesity ; Osteopontin/pharmacology/therapeutic use ; Microbiota ; }, abstract = {The gut microbiome is involved in metabolic disorders. Osteopontin (OPN), as a key cytokine, contributes to various inflammation-related diseases. The underlying role of OPN in the microbiome remains poorly understood. Here, we investigated whether OPN could modulate metabolic disorders by affecting gut microbiota. In our present study, we found that the expression of OPN was elevated in individuals with obesity compared to that observed in healthy controls. There was a positive correlation between plasma OPN levels and body mass index (BMI) in humans. Moreover, OPN significantly exacerbated lipid accumulation and metabolic disorders in high-fat diet (HFD)-fed mice. Importantly, OPN significantly aggravated HFD-induced gut dysbiosis with a key signature profile. Fecal microbiota transplantation also supported the role of OPN in HFD-induced metabolic disorders in a microbiota-dependent manner. Moreover, the microbiome shift of OPN-deficient mice would be compensated to resemble those of wild-type mice by feeding with either OPN-containing milk or recombinant OPN protein in vivo. Furthermore, metagenomic analysis showed that OPN induced a higher abundance of Dorea and a lower abundance of Lactobacillus, which were positively and negatively correlated with body weight, respectively. Indeed, the abundance of Dorea was significantly decreased after Lactobacillus administration, suggesting that OPN may regulate the intestinal abundance of Dorea by reducing the colonization of Lactobacillus. We further confirmed that OPN decreased the adhesion of Lactobacillus to intestinal epithelial cells through the Notch signaling pathway. This study suggested that OPN could exacerbate HFD-induced metabolic dysfunctions through the OPN-induced alteration of the gut microbiome. Therefore, OPN could be a potential therapeutic target for metabolic syndrome. IMPORTANCE Gut microbiota are involved in metabolic disorders. However, microbiome-based therapeutic interventions are not always effective, which might be due to interference of the host factors. Here, we identified a strong positive correlation between OPN levels and BMI in humans. Next, we confirmed that OPN could aggravate high-fat diet-induced metabolic disorders in mice. Importantly, we found that fecal microbiota transplantation from OPN-deficient mice significantly alleviated metabolic disorders in WT mice. OPN directly induces the remodeling of the gut microbiota both in vitro and in vivo. These findings indicate that OPN could contribute to metabolic disorders by inducing an alteration of gut microbiota. OPN regulated the relative abundance of Lactobacillus by decreasing the adhesion of Lactobacillus to intestinal epithelial cells through the Notch signaling pathway. These data identify OPN as a potential pharmaceutical target for weight control and for the treatment of metabolic disorders.}, }
@article {pmid36297012, year = {2022}, author = {Kaczynska, A and Klosinska, M and Chmiel, P and Janeczek, K and Emeryk, A}, title = {The Crosstalk between the Gut Microbiota Composition and the Clinical Course of Allergic Rhinitis: The Use of Probiotics, Prebiotics and Bacterial Lysates in the Treatment of Allergic Rhinitis.}, journal = {Nutrients}, volume = {14}, number = {20}, pages = {}, pmid = {36297012}, issn = {2072-6643}, mesh = {Humans ; Prebiotics ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Rhinitis, Allergic/therapy ; }, abstract = {Although massive progress in discovering allergic rhinitis (AR) aetiology has been made in recent years, its prevalence is still rising and it significantly impacts patients' lives. That is why further and non-conventional research elucidating the role of new factors in AR pathogenesis is needed, facilitating discoveries of new treatment approaches. One of these factors is the gut microbiota, with its specific roles in health and disease. This review presents the process of gut microbiota development, especially in early life, focusing on its impact on the immune system. It emphasizes the link between the gut microbiota composition and immune changes involved in AR development. Specifically, it elucidates the significant link between bacteria colonizing the gut and the Th1/Th2 imbalance. Probiotics, prebiotics and bacterial lysates, which are medications that restore the composition of intestinal bacteria and indirectly affect the clinical course of AR, are also discussed.}, }
@article {pmid36296961, year = {2022}, author = {Chen, YH and Yuan, W and Meng, LK and Zhong, JC and Liu, XY}, title = {The Role and Mechanism of Gut Microbiota in Pulmonary Arterial Hypertension.}, journal = {Nutrients}, volume = {14}, number = {20}, pages = {}, pmid = {36296961}, issn = {2072-6643}, support = {No. 82170302, 82070325, 92168117; 81770253; 91849111//National Major Research Plan Training Program of the National Natural Science Foundation of China/ ; QML20200305//Beijing Hospitals Authority Youth Program/ ; 7222138, 7222068; 7162069//Beijing Natural Science Foundation/ ; ysrh2022010, ysrh2022002, ysrh2022007//Reform and Development Program of Beijing Institute of Respiratory Medicine/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Pulmonary Arterial Hypertension ; Lipopolysaccharides ; Serotonin ; Dysbiosis/microbiology ; Fatty Acids, Volatile ; Inflammation ; *Probiotics ; }, abstract = {Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease characterized by increased pulmonary vascular resistance, pulmonary vasoconstriction, and right ventricular hypertrophy. Recent developments in genomics and metabolomics have gradually revealed the roles of the gut microbiota (GM) and its metabolites in cardiovascular diseases. Accumulating evidence reveals that the GM plays important roles in the occurrence and development of PAH. Gut microbiota dysbiosis directly increases the gut permeability, thereby facilitating pathological bacterial translocation and allowing translocation of bacterial products such as lipopolysaccharides from the gut into circulation. This process aggravates pulmonary perivascular inflammation and exacerbates PAH development through the endothelial-mesenchymal transition. Additionally, a shift in the composition of PAH also affects the gut metabolites. Changes in gut metabolites, such as decreased short-chain fatty acids, increased trimethylamine N-oxide, and elevated serotonin, contribute to pulmonary perivascular inflammation and pulmonary vascular remodeling by activating several signaling pathways. Studies of the intestinal microbiota in treating pulmonary hypertension have strengthened linkages between the GM and PAH. Probiotic therapy and fecal microbiota transplantation may supplement existing PAH treatments. In this article, we provide new insight for diagnosing, preventing and treating PAH by adding to the current knowledge of the intestinal flora mechanisms and its metabolites efficacy involved in PAH.}, }
@article {pmid36296186, year = {2022}, author = {Guzzo, GL and Mittinty, MN and Llamas, B and Andrews, JM and Weyrich, LS}, title = {Individuals with Inflammatory Bowel Disease Have an Altered Gut Microbiome Composition of Fungi and Protozoa.}, journal = {Microorganisms}, volume = {10}, number = {10}, pages = {}, pmid = {36296186}, issn = {2076-2607}, abstract = {It is known that the bacterial gut microbiome is altered in inflammatory bowel disease (IBD), but far less is known about the role of eukaryotic microorganisms in IBD. While eukaryotes are rarer than bacteria within the gastrointestinal environment, the current literature suggests that they may also be implicated in IBD. In our study, we characterized these often-neglected eukaryotic microbial communities by identifying fungi and protozoa in published shotgun stool metagenomes from 355 people with IBD (206 with Crohn's disease, 126 with ulcerative colitis, and 23 with IBD-unclassified) and 471 unaffected healthy individuals. The individuals with IBD had a higher prevalence of fungi, particularly Saccharomyces cerevisiae, and a lower prevalence of protozoa, particularly Blastocystis species (subtypes 1, 2, 3, and 4). Regression analysis showed that disease state, age, and BMI were associated with the prevalence and abundance of these two genera. We also characterized the eukaryotic gut microbiome in a shotgun stool metagenomic dataset from people with IBD who received fecal transplants, with samples pre- and post-transplantation, and from their donors. We found that in some FMT recipients, a single eukaryotic species remained stable over time, while in other recipients, the eukaryotic composition varied. We conclude that the eukaryotic gut microbiome is altered and varies over time in IBD, and future studies should aim to include these microbes when characterizing the gut microbiome in IBD.}, }
@article {pmid36296181, year = {2022}, author = {Jensen, C and Antonsen, MF and Lied, GA}, title = {Gut Microbiota and Fecal Microbiota Transplantation in Patients with Food Allergies: A Systematic Review.}, journal = {Microorganisms}, volume = {10}, number = {10}, pages = {}, pmid = {36296181}, issn = {2076-2607}, abstract = {The prevalence of food allergies (FAs) has increased considerably in recent decades, with the only available treatment being the avoidance of the specific food items causing the allergy. FAs may have a major impact on quality of life, and it is of great interest to explore new strategies to prevent and treat FAs. Some studies show an altered gut microbiota profile in individuals with FAs, and the modulation of gut microbiota is therefore proposed as a potential strategy for prevention and treatment. This systematic review aimed to investigate: (1) the gut microbiota profile in individuals with FAs compared to healthy individuals and (2) the effect of fecal microbiota transplantation (FMT) on gut microbiota profiles and/or allergy symptoms. A literature search was conducted in PubMed (Medline) on 5 April 2022. Of the 236 publications identified, 12 studies were included based on inclusion and exclusion criteria. Eleven of these studies reported results on the gut microbiota in children with FAs compared to healthy controls (HCs). The majority of studies (six studies) observed no difference in alpha diversity when comparing children with FAs to HCs; however, a difference in beta diversity was observed in five studies. At the phylum level, we observed a high abundance of Firmicutes (six studies) and Proteobacteria (five studies), whereas a low abundance of Bacteroidetes (5 studies) was observed in children with FAs compared to HCs. Of the 12 included studies, four explored the effect of FMT on gut microbiota and/or allergy symptoms. Three studies reported that transferring gut microbiota from children without FAs to germ-free mice, protected the mice against allergic reactions, whereas one study did not report findings on the allergic symptoms. The results on gut microbiota after FMT varied and were too divergent to draw any conclusions. Overall, our results suggest that there are differences in the gut microbiota profile in individuals with FAs compared to individuals without FAs. FMT seems to be a promising strategy to prevent allergic symptoms but needs to be further explored in animal and human models. As the findings in this review are based on a small number of studies (12 studies), further studies are warranted before any clear conclusions can be drawn regarding gut microbiota profiles and the effect of FMT on individuals with FAs.}, }
@article {pmid36293176, year = {2022}, author = {Varesi, A and Campagnoli, LIM and Fahmideh, F and Pierella, E and Romeo, M and Ricevuti, G and Nicoletta, M and Chirumbolo, S and Pascale, A}, title = {The Interplay between Gut Microbiota and Parkinson's Disease: Implications on Diagnosis and Treatment.}, journal = {International journal of molecular sciences}, volume = {23}, number = {20}, pages = {}, pmid = {36293176}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Parkinson Disease/diagnosis/therapy/pathology ; Dysbiosis/therapy ; Anti-Bacterial Agents ; Biomarkers ; }, abstract = {The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain function and has an important impact on the development of neurodegenerative diseases. In Parkinson's disease (PD), gastrointestinal symptoms often precede the onset of motor and non-motor manifestations, and alterations in the GM composition accompany disease pathogenesis. Several studies have been conducted to unravel the role of dysbiosis and intestinal permeability in PD onset and progression, but the therapeutic and diagnostic applications of GM modifying approaches remain to be fully elucidated. After a brief introduction on the involvement of GMBA in the disease, we present evidence for GM alterations and leaky gut in PD patients. According to these data, we then review the potential of GM-based signatures to serve as disease biomarkers and we highlight the emerging role of probiotics, prebiotics, antibiotics, dietary interventions, and fecal microbiota transplantation as supportive therapeutic approaches in PD. Finally, we analyze the mutual influence between commonly prescribed PD medications and gut-microbiota, and we offer insights on the involvement also of nasal and oral microbiota in PD pathology, thus providing a comprehensive and up-to-date overview on the role of microbial features in disease diagnosis and treatment.}, }
@article {pmid36291139, year = {2022}, author = {Svensson, CK and Cold, F and Ribberholt, I and Zangenberg, M and Mirsepasi-Lauridsen, HC and Petersen, AM and Helms, M}, title = {The Efficacy of Faecal Microbiota Transplant and Rectal Bacteriotherapy in Patients with Recurrent Clostridioides difficile Infection: A Retrospective Cohort Study.}, journal = {Cells}, volume = {11}, number = {20}, pages = {}, pmid = {36291139}, issn = {2073-4409}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile ; Retrospective Studies ; *Clostridium Infections/therapy ; Treatment Outcome ; }, abstract = {The most effective treatment for recurrent Clostridioides difficile infection (CDI) is faecal microbiota transplantation (FMT); however, the optimal route of administration is thus far unknown. This retrospective cohort study of 343 patients sought to evaluate the efficacy of treatment with FMT capsules, FMT enema, and rectal bacteriotherapy (RBT) during a five-year period. The primary endpoint was clinical resolution from CDI after eight weeks, and secondary endpoints were time to recurrence and death during the follow-up period. The proportion of patients with clinical resolution was 79.9% in the FMT capsule group, 53.3% in the FMT enema group, and 61.8% in the RBT group, corresponding to an adjusted odds ratio of 3.79 (CI: 1.82 to 8.26) in the FMT capsule group compared with FMT enema, and 2.92 (CI: 1.49 to 6.03) compared with RBT. The hazards ratio for recurrence within the first 12 months of follow-up was 0.24 (CI: 0.06 to 0.89) in the FMT capsule group compared with FMT enema, and 0.26 (CI: 0.08 to 0.91) compared with RBT. There was no difference in mortality. In conclusion, FMT capsules were more effective than both FMT enema and RBT as treatment of recurrent CDI and reduced the risk of further recurrences.}, }
@article {pmid36289668, year = {2022}, author = {Shin, J and Lee, JH and Park, SH and Cha, B and Kwon, KS and Kim, H and Shin, YW}, title = {Efficacy and Safety of Fecal Microbiota Transplantation for Clearance of Multidrug-Resistant Organisms under Multiple Comorbidities: A Prospective Comparative Trial.}, journal = {Biomedicines}, volume = {10}, number = {10}, pages = {}, pmid = {36289668}, issn = {2227-9059}, support = {DFY2115P//Daewoong Pharmaceutical (South Korea)/ ; 2021R1F1A1060099//National Research Foundation of Korea/ ; }, abstract = {Fecal microbiota transplantation (FMT) could decolonize multidrug-resistant organisms. We investigated FMT effectiveness and safety in the eradication of carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant enterococci (VRE) intestinal colonization. A prospective non-randomized comparative study was performed with 48 patients. FMT material (60 g) was obtained from a healthy donor, frozen, and administered via endoscopy. The primary endpoint was 1-month decolonization, and secondary endpoints were 3-month decolonization and adverse events. Microbiota analysis of fecal samples was performed using 16S rRNA sequencing. Intention-to-treat analysis revealed overall negative conversion between the FMT and control groups at 1 (26% vs. 10%, p = 0.264) and 3 (52% vs. 24%, p = 0.049) months. The 1-month and 3-month CRE clearance did not differ significantly by group (36% vs. 10%, p = 0.341; and 71% vs. 30%, p = 0.095, respectively). Among patients with VRE, FMT was ineffective for 1-month or 3-month negative conversion (13% vs. 9%, p > 0.999; and 36% vs. 18%, p = 0.658, respectively) However, cumulative overall negative-conversion rate was significantly higher in the FMT group (p = 0.037). Enterococcus abundance in patients with VRE significantly decreased following FMT. FMT may be effective at decolonizing multidrug-resistant organisms in the intestinal tract.}, }
@article {pmid36289064, year = {2022}, author = {Nzabarushimana, E and Tang, H}, title = {Functional profile of host microbiome indicates Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2135963}, pmid = {36289064}, issn = {1949-0984}, support = {R01 AI143254/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Clostridioides difficile/genetics ; *Gastrointestinal Microbiome ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation/methods ; *Microbiota ; Anti-Bacterial Agents/therapeutic use ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection (CDI) is a gastro-intestinal (GI) infection that illustrates how perturbations in symbiotic host-microbiome interactions render the GI tract vulnerable to the opportunistic pathogens. CDI also serves as an example of how such perturbations could be reversed via gut microbiota modulation mechanisms, especially fecal microbiota transplantation (FMT). However, microbiome-mediated diagnosis of CDI remains understudied. Here, we evaluated the diagnostic capabilities of the fecal microbiome on the prediction of CDI. We used the metagenomic sequencing data from ten previous studies, encompassing those acquired from CDI patients treated by FMT, CDI-negative patients presenting other intestinal health conditions, and healthy volunteers taking antibiotics. We designed a hybrid species/function profiling approach that determines the abundances of microbial species in the community contributing to its functional profile. These functionally informed taxonomic profiles were then used for classification of the microbial samples. We used logistic regression (LR) models using these features, which showed high prediction accuracy (with an average AUC≥0.91), substantiating that the species/function composition of the gut microbiome has a robust diagnostic prediction of CDI. We further assessed the confounding impact of antibiotic therapy on CDI prediction and found that it is distinguishable from the CDI impact. Finally, we devised a log-odds score computed from the output of the LR models to quantify the likelihood of CDI in a gut microbiome sample and applied it to evaluating the effectiveness of FMT based on post-FMT microbiome samples. The results showed that the gut microbiome of patients exhibited a gradual but steady improvement after receiving successful FMT, indicating the restoration of the normal microbiome functions.}, }
@article {pmid36287379, year = {2022}, author = {Khanna, S and Assi, M and Lee, C and Yoho, D and Louie, T and Knapple, W and Aguilar, H and Garcia-Diaz, J and Wang, GP and Berry, SM and Marion, J and Su, X and Braun, T and Bancke, L and Feuerstadt, P}, title = {Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial with a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection.}, journal = {Drugs}, volume = {82}, number = {15}, pages = {1527-1538}, pmid = {36287379}, issn = {1179-1950}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Humans ; *Clostridioides difficile ; Bayes Theorem ; Diarrhea/drug therapy/prevention &amp; control ; *Clostridium Infections/drug therapy/prevention &amp; control ; Anti-Bacterial Agents/adverse effects ; Treatment Outcome ; Recurrence ; Fecal Microbiota Transplantation/adverse effects ; }, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection, associated with dysbiosis of gut microbiota, has substantial disease burden in the USA. RBX2660 is a live biotherapeutic product consisting of a broad consortium of microbes prepared from human stool that is under investigation for the reduction of recurrent C. difficile infection.<br><br>METHODS: A randomized, double-blind, placebo-controlled, phase III study, with a Bayesian primary analysis integrating data from a previous phase IIb study, was conducted. Adults who had one or more C. difficile infection recurrences with a positive stool assay for C. difficile and who were previously treated with standard-of-care antibiotics were randomly assigned 2:1 to receive a subsequent blinded, single-dose enema of RBX2660 or placebo. The primary endpoint was treatment success, defined as the absence of C. difficile infection diarrhea within 8 weeks of study treatment.<br><br>RESULTS: Of the 320 patients screened, 289 were randomly assigned and 267 received blinded treatment (n = 180, RBX2660; n = 87, placebo). Original model estimates of treatment success were 70.4% versus 58.1% with RBX2660 and placebo, respectively. However, after aligning the data to improve the exchangeability and interpretability of the Bayesian analysis, the model-estimated treatment success rate was 70.6% with RBX2660 versus 57.5% with placebo, with an estimated treatment effect of 13.1% and a posterior probability of superiority of 0.991. More than 90% of the participants who achieved treatment success at 8 weeks had sustained response through 6 months in both the RBX2660 and the placebo groups. Overall, RBX2660 was well tolerated, with manageable adverse events. The incidence of treatment-emergent adverse events was higher in RBX2660 recipients compared with placebo and was mostly driven by a higher incidence of mild gastrointestinal events.<br><br>CONCLUSIONS: RBX2660 is a safe and effective treatment to reduce recurrent C. difficile infection following standard-of-care antibiotics with a sustained response through 6 months.<br><br>CLINICAL TRIAL REGISTRATION: NCT03244644; 9 August, 2017.}, }
@article {pmid36284437, year = {2023}, author = {Li, Z and Liang, H and Hu, Y and Lu, L and Zheng, C and Fan, Y and Wu, B and Zou, T and Luo, X and Zhang, X and Zeng, Y and Liu, Z and Zhou, Z and Yue, Z and Ren, Y and Li, Z and Su, Q and Xu, P}, title = {Gut bacterial profiles in Parkinson's disease: A systematic review.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {29}, number = {1}, pages = {140-157}, pmid = {36284437}, issn = {1755-5949}, mesh = {Humans ; Animals ; Mice ; *Parkinson Disease ; *Gastrointestinal Microbiome ; Bacteria ; Feces/microbiology ; Fatty Acids, Volatile ; }, abstract = {INTRODUCTION: Recent advances have highlighted the relationships between gut dysbiosis and Parkinson's disease (PD). Microbiota transplantation from PD patients to mice can induce increased alpha-synuclein-mediated motor deficits. Human studies have identified differences in the gut microbiota of PD patients compared to healthy controls. We undertook a systematic review to evaluate the available evidence for the involvement of gut bacteria in the etiology of PD.<br><br>METHODS: The PubMed databank, the China National Knowledge Infrastructure databank, and Wanfang Data were searched from inception until June 2021 to identify human case-control studies that investigated relationships between PD and microbiota quantified from feces. We evaluated the resulting studies focusing on bacterial taxa that were different between PD patients and healthy controls.<br><br>RESULTS: Twenty-six studies were found in which 53 microbial families and 98 genera exhibited differences between patients with PD and healthy controls. The genera identified by more than two studies as increased in PD were Bifidobacterium, Alistipes, Christensenella, Enterococcus, Oscillospira, Bilophila, Desulfovibrio, Escherichia/Shigella, and Akkermansia, while Prevotella, Blautia, Faecalibacterium, Fusicatenibacter, and Haemophilus had three or more reports of being lower in PD patients. More than one report demonstrated that Bacteroides, Odoribacter, Parabacteroides, Butyricicoccus, Butyrivibrio, Clostridium, Coprococcus, Lachnospira, Lactobacillus, Megasphaera, Phascolarctobacterium, Roseburia, Ruminococcus, Streptococcus, and Klebsiella were altered in both directions.<br><br>CONCLUSION: Our review shows that the involvement of the gut microbiome in the etiology of PD may involve alterations of short-chain fatty acids (SCFAs)-producing bacteria and an increase in putative gut pathobionts. SCFAs-producing bacteria may vary above or below an "optimal range," causing imbalances. Considering that Bifidobacterium, Lactobacillus, and Akkermansia are beneficial for human health, increased Bifidobacterium and Lactobacillus in the PD gut microbiome may be associated with PD medications, especially COMT inhibitors, while a high level of Akkermansia may be associated with aging.}, }
@article {pmid36281730, year = {2022}, author = {Li, P and Liu, Y and Zhao, J and Pan, W and He, Y and Fu, S and Liu, Y and Xu, YJ}, title = {Salecan ameliorates liver injury by regulating gut microbiota and its metabolites.}, journal = {Food &amp; function}, volume = {13}, number = {22}, pages = {11744-11757}, doi = {10.1039/d2fo02210a}, pmid = {36281730}, issn = {2042-650X}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *beta-Glucans/chemistry ; Liver/metabolism ; Oxidative Stress ; Mice, Inbred C57BL ; }, abstract = {Salecan, a natural β-glucan consisting of seven residues linked by β-(1→3)/α-(1→3) glycosidic bonds, is one of the novel food ingredients approved in China. β-Glucan has a variety of health-improving effects, yet its mechanism against liver injury remains poorly understood. β-Glucan can induce shifts in the gut microbiota and show health benefits; however, whether modulation of the gut microbiota by β-glucan is associated with its benefits remains unclear. Here, the hepatoprotective effect and potential mechanism of salecan supplementation using a model of CCl4-induced liver injury were investigated. After 8 weeks of treatment, salecan alleviated liver injury by regulating oxidative stress and activating the Nrf2 signaling pathway. In addition, salecan treatment modulated the composition of the gut microbiota, and the antibiotic cocktail treatment indicated that the hepatoprotective effect of salecan was dependent on the gut microbiota. Fecal microbiota transplantation was used to further verify this mechanism, and we confirmed that microbial colonization partially alleviated liver injury. Besides, microbiota-derived metabolites of salecan also contributed to the hepatoprotective effect of salecan against liver injury and inhibited oxidative stress. These findings supported that salecan intervention attenuated liver injury by regulating the gut microbiota and its metabolites.}, }
@article {pmid36280756, year = {2023}, author = {Yao, H and Zhang, D and Yu, H and Yuan, H and Shen, H and Lan, X and Liu, H and Chen, X and Meng, F and Wu, X and Zhang, G and Wang, X}, title = {Gut microbiota regulates chronic ethanol exposure-induced depressive-like behavior through hippocampal NLRP3-mediated neuroinflammation.}, journal = {Molecular psychiatry}, volume = {28}, number = {2}, pages = {919-930}, pmid = {36280756}, issn = {1476-5578}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; NLR Family, Pyrin Domain-Containing 3 Protein ; Neuroinflammatory Diseases ; Ethanol/pharmacology ; Depression/psychology ; Inflammasomes/metabolism ; Hippocampus/metabolism ; }, abstract = {Chronic ethanol exposure (CEE), which can lead to neuroinflammation, is an increasing risk factor for depression disorder, but the underlying mechanism is not clear. Recent observations have revealed the associations among psychiatric disorders, ethanol exposure and alterations of the gut microbiota. Here, we found that CEE induced depressive-like behavior, which could be alleviated by probiotics and transferred from donor to recipient mice by fecal microbiota transplantation (FMT). Neuroinflammation and the activation of the NLRP3 inflammasome were also observed in recipient mice. The downregulation of NLRP3 in the hippocampus mitigated CEE-induced depressive-like behavior and neuroinflammation but had no significant effect on FMT recipient mice. Moreover, elevated serum inflammatory factors in recipient mice showed a significant mediation effect between the gut microbiota and depressive-like behavior. Together, our study findings indicate that the gut microbiota contributes to both hippocampal NLRP3-mediated neuroinflammation and depressive-like behavior induced by CEE, which may open avenues for potential interventions against CEE-associated psychiatric disorders.}, }
@article {pmid36280324, year = {2022}, author = {Gupta, A and Singh, V and Mani, I}, title = {Dysbiosis of human microbiome and infectious diseases.}, journal = {Progress in molecular biology and translational science}, volume = {192}, number = {1}, pages = {33-51}, doi = {10.1016/bs.pmbts.2022.06.016}, pmid = {36280324}, issn = {1878-0814}, mesh = {Humans ; Dysbiosis ; Prebiotics ; *Gastrointestinal Microbiome ; *Microbiota ; *Probiotics ; Bacteria ; *Communicable Diseases ; }, abstract = {Since birth, the human body gets colonized by various communities of symbiotic or commensal microorganisms and they persist till the death of an individual. The human microbiome is comprised of the genomes of microorganisms such as viruses, archaea, eukaryotes, protozoa, and, most remarkably, bacteria. The development of "omics" technologies gave way to the Human Microbiome Project (HMP) which aimed at exploring the collection of microbial genes and genomes inhabiting the human body. Eubiosis, i.e., a healthy and balanced composition of such microbes contributes to the metabolic function, protection against pathogens and provides nutrients and energy to the host. Whereas, an imbalance in the diversity of microorganisms, termed dysbiosis, greatly influences the state of health and disease. This chapter summarizes the impact of gut bacteria on the well-being of humans and highlights the protective role played by the human microbiota during bacterial and viral infections. The condition of dysbiosis and how it plays a role in the establishment of various infections and metabolic disorders such as Clostridioides difficile infection (CFI), inflammatory bowel disease (IBD), cancer, periodontitis, and obesity are described in detail. Further, treatments such as fecal transplantation, probiotics, prebiotics, phage therapy, and CRISPR/Cas system, which target gut microbiota during digestive diseases are also discussed.}, }
@article {pmid36280104, year = {2023}, author = {van Lier, YF and Rolling, T and Armijo, GK and Zhai, B and Haverkate, NJE and Meijer, E and Nur, E and Blom, B and Peled, JU and van den Brink, MRM and Hohl, TM and Hazenberg, MD and Markey, KA}, title = {Profiling the Fungal Microbiome after Fecal Microbiota Transplantation for Graft-versus-Host Disease: Insights from a Phase 1 Interventional Study.}, journal = {Transplantation and cellular therapy}, volume = {29}, number = {1}, pages = {63.e1-63.e5}, pmid = {36280104}, issn = {2666-6367}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R21 AI156157/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; R01 AI100288/AI/NIAID NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Mycobiome ; *Graft vs Host Disease/therapy ; Feces/microbiology ; *Microbiota ; Bacteria/genetics ; }, abstract = {Disruption of the intestinal bacterial microbiota is frequently observed in the context of allogeneic hematopoietic cell transplantation (HCT) and is particularly pronounced in patients who develop graft-versus-host disease (GVHD). Donor fecal microbiota transplantation (FMT) restores gut microbial diversity and reduces GVHD in HCT recipients. The composition of the intestinal fungal community in patients with GVHD, and whether fungal taxa are transferred during FMT are currently unknown. We performed a secondary analysis of our clinical trial of FMT in patients with steroid-refractory GVHD with a focus on the mycobiota. We characterized the fecal mycobiota of 17 patients and healthy FMT donors using internal transcribed spacer amplicon sequencing. The donor who provided the majority of FMT material in our study represents an n-of-one study of the intestinal flora over time. In this donor, mycobiota composition fluctuated over time while the bacterial microbiota remained stable over 16 months. Fungal DNA was detected more frequently in baseline stool samples from patients with steroid-refractory GVHD than in patients with steroid-dependent GVHD. We could detect fungal taxa in the majority of samples but did not see evidence of mycobiota transfer from donor to recipient. Our study demonstrates the feasibility of profiling the mycobiota alongside the more traditional bacterial microbiota, establishes the methodology, and provides a first insight into the mycobiota composition of patients with GVHD.}, }
@article {pmid36279081, year = {2022}, author = {Zhang, J and Wu, K and Shi, C and Li, G}, title = {Cancer Immunotherapy: Fecal Microbiota Transplantation Brings Light.}, journal = {Current treatment options in oncology}, volume = {23}, number = {12}, pages = {1777-1792}, pmid = {36279081}, issn = {1534-6277}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; Immune Checkpoint Inhibitors ; Immunotherapy/adverse effects ; *Neoplasms/etiology/therapy ; *Gastrointestinal Microbiome ; }, abstract = {Immunotherapy is revolutionizing tumor treatment by activating the immune response to tumors. Among them, immunotherapy represented by immune checkpoint inhibitors is considered to be a milestone in tumor treatment. It has revolutionized the management of advanced malignant tumors by activating T cells, promoting cytotoxic signaling pathways, and killing tumor cells, effectively improving the overall survival of patients. However, resistance to immunotherapy and immune-related adverse events remain challenges for immunotherapy. It has been demonstrated in previous studies that modulating intestinal microbiota can enhance immunotherapy response and reduce complications. Currently, the more mature method for microbiota regulation is fecal microbiota transplantation, which involves transfering a donor's microbiome to the recipient in the form of capsules or fecal microbiota suspension to restore the richness of the recipient's intestinal microbiota. In terms of cancer immunotherapy, fecal microbiota transplantation in patients who fail to respond to immune checkpoint inhibitors is expected to produce better prognosis for patients.}, }
@article {pmid36278360, year = {2022}, author = {Chan, DG and Ventura, K and Villeneuve, A and Du Bois, P and Holahan, MR}, title = {Exploring the Connection Between the Gut Microbiome and Parkinson's Disease Symptom Progression and Pathology: Implications for Supplementary Treatment Options.}, journal = {Journal of Parkinson's disease}, volume = {12}, number = {8}, pages = {2339-2352}, pmid = {36278360}, issn = {1877-718X}, mesh = {Humans ; *Parkinson Disease/metabolism ; *Gastrointestinal Microbiome/physiology ; Homeostasis ; Central Nervous System/metabolism ; *Enteric Nervous System/metabolism ; }, abstract = {The contribution of the microbiota to induce gastrointestinal inflammation is hypothesized to be a key component of alpha-synuclein (aSyn) aggregation within the gastrointestinal (GI) tract in the pathological progression of Parkinson's disease (PD). The function of the GI tract is governed by a system of neurons that form part of the enteric nervous system (ENS). The ENS hosts 100-500 million nerve cells within two thin layers lining the GI tract. The gut-brain axis (GBA) is the major communication pathway between the ENS and the central nervous system. It has become increasingly clear that the microbiota in the gut are key regulators of GBA function and help to maintain homeostasis in the immune and endocrine systems. The GBA may act as a possible etiological launching pad for the pathogenesis of age-related neurodegenerative diseases, such as PD, because of an imbalance in the gut microbiota. PD is a multi-faceted illness with multiple biological, immunological, and environmental factors contributing to its pathological progression. Interestingly, individuals with PD have an altered gut microbiota compared to healthy individuals. However, there is a lack of literature describing the relationship between microbiota composition in the gut and symptom progression in PD patients. This review article examines how the pathology and symptomology of PD may originate from dysregulated signaling in the ENS. We then discuss by targeting the imbalance within the gut microbiota such as prebiotics and probiotics, some of the prodromal symptoms might be alleviated, possibly curtailing the pathological spread of aSyn and ensuing debilitating motor symptoms.}, }
@article {pmid36275423, year = {2022}, author = {Hamblin, H and Gunaratne, AW and Clancy, A and Pilarinos, D and LeBusque, A and Dawson, MVM and Borody, TJ}, title = {Pre-Antibiotic Treatment Followed by Prolonged Repeated Faecal Microbiota Transplantation Improves Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome: An Observational Australian Clinical Experience.}, journal = {Gastroenterology research and practice}, volume = {2022}, number = {}, pages = {6083896}, pmid = {36275423}, issn = {1687-6121}, abstract = {BACKGROUND: The use of faecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) has frequently failed to induce long-term symptomatic improvement. The use of multiple FMT infusions is one proposed mechanism through which the efficacy of FMT can be amplified.<br><br>AIMS: To evaluate the safety and efficacy of a novel six-month FMT treatment protocol in IBS.<br><br>METHODS: Patients diagnosed with IBS confirmed by Rome IV Criteria were recruited for single-centre, single-arm, prospective clinical observational study. Participants received one colonoscopically delivered FMT followed by 36 rectal enemas across a six-month period. Validated abdominal symptoms and Short-Form (SF-36) Quality of Life (QOL) questionnaires were collected at baseline, week-12, week-24, and week-56, respectively. Wilcoxon matched-pairs signed-rank tests were conducted to compare differences in abdominal symptom and SF-36 QOL scores over the follow-up timepoints. Statistical significance was set at 5%.<br><br>RESULTS: Sixty participants diagnosed with IBS [IBS-constipation (n = 27), IBS-diarrhoea (n = 18), and IBS-mixed (n = 15)] received the six-month FMT treatment. IBS symptom severity reduction was achieved in up to 61% of respondents at week-12, 64% of respondents at week-24, and maintained in up to 75% of respondents at week-52. Long-term reduction in symptom severity was associated with an increase in QOL, achieved in up to 64% of respondents at week-52 when compared to baseline. Adverse events were experienced in 28% of participants, though they were both transient and mild in nature.<br><br>CONCLUSIONS: Six-month sustained FMT appears to be both safe and effective in the short- and long-term alleviation of IBS associated symptoms as well as improving participant QOL.}, }
@article {pmid36270679, year = {2022}, author = {Mehrotra, T and Maulik, SK}, title = {Hepatic drug metabolism and gut microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {207-228}, doi = {10.1016/bs.pmbts.2022.07.005}, pmid = {36270679}, issn = {1878-0814}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; *Diabetes Mellitus, Type 2 ; Fecal Microbiota Transplantation ; *Probiotics ; }, abstract = {This chapter focuses on intestinal microbiota and its effect on drug metabolism. Here, we discussed about different drugs which are metabolized either by some enzymes or gut microbiota and their mechanism. Nowadays, consuming drugs without a doctor's prescription is common. This chapter will make people aware about its negative consequences and how it is related to gut microbiota dysbiosis. Intestinal disorders like inflammatory bowel disease (IBD), colorectal cancer (CRC) and metabolic disorders such as obesity and type 2 diabetes mellitus (T2D) are found to be affected with gut microbiota dysbiosis. To address this issue, we discussed a variety of strategies such as fecal microbiota transplantation (FMT), probiotics and antibiotic stewardship programs which are commonly used to tackle this problem.}, }
@article {pmid36270678, year = {2022}, author = {Purohit, A and Alam, MJ and Kandiyal, B and Shalimar,  and Das, B and Banerjee, SK}, title = {Gut microbiome and non-alcoholic fatty liver disease.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {187-206}, doi = {10.1016/bs.pmbts.2022.07.004}, pmid = {36270678}, issn = {1878-0814}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Non-alcoholic Fatty Liver Disease/therapy/complications/microbiology ; Prebiotics ; Dysbiosis ; Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; }, abstract = {The human gastrointestinal tract (GIT) contains a dynamic and diverse collection of bacteria, archaea, and fungi termed the "gut microbiome." The gut microbiome has a major impact on the host during homeostasis and disease. The connection between both the host and the microbiome is complex, although its manipulation may assist prevent or treating a multitude of morbidities. These microorganisms play a critical role in the host's energy metabolism and homeostasis. According to new research, the microbes in the gastrointestinal tract play a substantial role in host health, and alterations in its composition and function might lead to the emergence of metabolic disorders like non-alcoholic fatty liver disease (NAFLD). The resilience of the GIT microbial ecology and its tolerance to perturbation are robust but not ideal. Several factors may disrupt the GIT microbiome's homeostasis leading to dysbiosis, characterized by an imbalanced equilibrium and perturbations in gut homeostasis. Irritable bowel disease (IBD), malnutrition, and metabolic disorders, such as NAFLD, have been associated with the dysbiotic gut microbiome. Recent evidence suggests that utilizing medications, prebiotics, probiotics, and fecal microbiota transplantation (FMT) to manipulate the microbiome could be a viable method for treating NAFLD.}, }
@article {pmid36270677, year = {2022}, author = {Patel, S and Seshadri, S and Dalai, S}, title = {Gut microbiome and type 2 diabetes.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {175-185}, doi = {10.1016/bs.pmbts.2022.06.029}, pmid = {36270677}, issn = {1878-0814}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 2/metabolism/microbiology ; Bacteria/metabolism ; Bile Acids and Salts/metabolism ; Anti-Bacterial Agents ; Glucose/metabolism ; Lipids ; }, abstract = {Dietary patterns with excess caloric have shaped a complex metabolic disorders like type 2 diabetes (T2D). T2D involves complications in the metabolism of glucose, lipid, cholesterol and their storage. Along with the metabolic dysregulation, systemic inflammation is also the reason for Insulin Resistance and T2D. The importance of gut microbiota has recently been highlighted. It establishes a link between dietary patterns and the types of bacteria that overgrow and modify fermentation bi-products such as SCFA, secondary bile acids, and mucosal immune cells. These changes have a direct impact on the liver's metabolism and immune system. As a result, using Pre-Pro-biotics to manage microbiota can assist overcome or lessening disease symptoms. Antibiotics are currently employed to produce a germ-free environment or to eradicate specific types of bacteria in order to better understand the role of microflora. This chapter covers the basics of good bacteria, as well as the mechanisms that they work on.}, }
@article {pmid36269743, year = {2022}, author = {Slanzon, GS and Ridenhour, BJ and Parrish, LM and Trombetta, SC and Moore, DA and Sischo, WM and McConnel, CS}, title = {Effects of a farm-specific fecal microbial transplant (FMT) product on clinical outcomes and fecal microbiome composition in preweaned dairy calves.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0276638}, pmid = {36269743}, issn = {1932-6203}, mesh = {Cattle ; Animals ; Farms ; *Fecal Microbiota Transplantation/methods ; Feces ; *Microbiota ; Anti-Bacterial Agents ; }, abstract = {Gastrointestinal disease (GI) is the most common illness in pre-weaned dairy calves. Therefore, effective strategies to manipulate the microbiome of dairy calves under commercial dairy operations are of great importance to improve animal health and reduce antimicrobial usage. The objective of this study was to develop a farm-specific FMT product and to investigate its effects on clinical outcomes and fecal microbial composition of dairy calves. The FMT product was derived from feces from healthy donors (5-24 days of age) raised in the same calf ranch facility as the FMT recipients. Healthy and diarrheic calves were randomly enrolled to a control (n = 115) or FMT (n = 112) treatment group (~36 g of processed fecal matter once daily for 3 days). Fecal samples were collected at enrollment and again 9 days later after the first FMT dose. Although the FMT product was rich in organisms typically known for their beneficial probiotic properties, the FMT therapy did not prevent or ameliorate GI disease in dairy calves. In fact, calves that received FMT were less likely to recover from GI disease, and more likely to die due to GI disease complications. Fecal microbial community analysis revealed an increase in the alpha-diversity in FMT calves; however, no major differences across treatment groups were observed in the beta-diversity analysis. Calves that received FMT had higher relative abundance of an uncultured organism of the genus Lactobacillus and Lactobacillus reuteri on day 10. Moreover, FMT calves had lower relative abundance of Clostridium nexile and Bacteroides vulgatus on day 10. Our results indicate the need to have an established protocol when developing FMT products, based on rigorous inclusion and exclusion criteria for the selection of FMT donors free of potential pathogens, no history of disease or antibiotic treatment.}, }
@article {pmid36267243, year = {2022}, author = {Huang, W and Zhu, L and Song, W and Zhang, M and Teng, L and Wu, M}, title = {Crosstalk between the Gut and Brain in Ischemic Stroke: Mechanistic Insights and Therapeutic Options.}, journal = {Mediators of inflammation}, volume = {2022}, number = {}, pages = {6508046}, pmid = {36267243}, issn = {1466-1861}, mesh = {Humans ; Prebiotics ; *Ischemic Stroke ; Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Brain/metabolism ; *Stroke/therapy/metabolism ; }, abstract = {There has been a significant amount of interest in the past two decades in the study of the evolution of the gut microbiota, its internal and external impacts on the gut, and risk factors for cerebrovascular disorders such as cerebral ischemic stroke. The network of bidirectional communication between gut microorganisms and their host is known as the microbiota-gut-brain axis (MGBA). There is mounting evidence that maintaining gut microbiota homeostasis can frequently enhance the effectiveness of ischemic stroke treatment by modulating immune, metabolic, and inflammatory responses through MGBA. To effectively monitor and cure ischemic stroke, restoring a healthy microbial ecology in the gut may be a critical therapeutic focus. This review highlights mechanistic insights on the MGBA in disease pathophysiology. This review summarizes the role of MGBA signaling in the development of stroke risk factors such as aging, hypertension, obesity, diabetes, and atherosclerosis, as well as changes in the microbiota in experimental or clinical populations. In addition, this review also examines dietary changes, the administration of probiotics and prebiotics, and fecal microbiota transplantation as treatment options for ischemic stroke as potential health benefits. It will become more apparent how the MGBA affects human health and disease with continuing advancements in this emerging field of biomedical sciences.}, }
@article {pmid36266965, year = {2023}, author = {Zhou, LJ and Lin, WZ and Liu, T and Chen, BY and Meng, XQ and Li, YL and Du, LJ and Liu, Y and Qian, YC and Zhu, YQ and Duan, SZ}, title = {Oral Pathobionts Promote MS-like Symptoms in Mice.}, journal = {Journal of dental research}, volume = {102}, number = {2}, pages = {217-226}, doi = {10.1177/00220345221128202}, pmid = {36266965}, issn = {1544-0591}, mesh = {Mice ; Animals ; *Encephalomyelitis, Autoimmune, Experimental ; *Multiple Sclerosis ; Mice, Inbred C57BL ; Th17 Cells ; }, abstract = {Dysbiotic oral microbiota has been associated with multiple sclerosis. However, the role and mechanism of oral microbiota in the development of multiple sclerosis are still elusive. Here, we demonstrated that ligature-induced periodontitis (LIP) aggravated experimental autoimmune encephalomyelitis (EAE) in mice, and this was likely dependent on the expansion of T helper 17 (Th17) cells. LIP increased the splenic richness of Enterobacter sp., which was able to induce the expansion of splenic Th17 cells and aggravate EAE in mice. LIP also led to enrichment of Erysipelotrichaceae sp. in the gut and increased Th17 cells in the large intestinal lamina propria of EAE mice. Fecal microbiota transplantation from EAE mice with LIP also promoted EAE symptoms. In conclusion, periodontitis exacerbates EAE, likely through ectopic colonization of oral pathobionts and expansion of Th17 cells.}, }
@article {pmid36264933, year = {2022}, author = {Bénard, MV and de Bruijn, CMA and Fenneman, AC and Wortelboer, K and Zeevenhoven, J and Rethans, B and Herrema, HJ and van Gool, T and Nieuwdorp, M and Benninga, MA and Ponsioen, CY}, title = {Challenges and costs of donor screening for fecal microbiota transplantations.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0276323}, pmid = {36264933}, issn = {1932-6203}, mesh = {Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Fecal Microbiota Transplantation ; Donor Selection ; SARS-CoV-2 ; *COVID-19 ; Feces ; *Clostridium Infections ; }, abstract = {BACKGROUND: The increasing interest to perform and investigate the efficacy of fecal microbiota transplantation (FMT) has generated an urge for feasible donor screening. We report our experience with stool donor recruitment, screening, follow-up, and associated costs in the context of clinical FMT trials.<br><br>METHODS: Potential stool donors, aged between 18-65 years, underwent a stepwise screening process starting with an extensive questionnaire followed by feces and blood investigations. When eligible, donors were rescreened for MDROs and SARS-CoV-2 every 60-days, and full rescreening every 4-6 months. The costs to find and retain a stool donor were calculated.<br><br>RESULTS: From January 2018 to August 2021, 393 potential donors underwent prescreening, of which 202 (51.4%) did not proceed primarily due to loss to follow-up, medication use, or logistic reasons (e.g. COVID-19 measures). 191 potential donors filled in the questionnaire, of which 43 (22.5%) were excluded. The remaining 148 candidates underwent parasitology screening: 91 (61.5%) were excluded, mostly due to Dientamoeba fragilis and/or high amounts of Blastocystis spp. After additional feces investigations 18/57 (31.6%) potential donors were excluded (mainly for presence of Helicobacter Pylori and ESBL-producing organisms). One donor failed serum testing. Overall, 38 out of 393 (10%) potential donors were enrolled. The median participation time of active stool donors was 13 months. To recruit 38 stool donors, &#x20ac;64.112 was spent.<br><br>CONCLUSION: Recruitment of stool donors for FMT is challenging. In our Dutch cohort, failed eligibility of potential donors was often caused by the presence of the protozoa Dientamoeba fragilis and Blastocystis spp.. The exclusion of potential donors that carry these protozoa, especially Blastocystis spp., is questionable and deserves reconsideration. High-quality donor screening is associated with substantial costs.}, }
@article {pmid36264425, year = {2022}, author = {Kelly-Goss, MR and Badran, YR and Dougan, M}, title = {Update on Immune Checkpoint Inhibitor Enterocolitis.}, journal = {Current gastroenterology reports}, volume = {24}, number = {12}, pages = {171-181}, pmid = {36264425}, issn = {1534-312X}, support = {K08 DK114563/DK/NIDDK NIH HHS/United States ; R01 AI169188/AI/NIAID NIH HHS/United States ; 1R01AI169188//National Institute of Allergy and Infectious Diseases/ ; 1K08DK114563/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Immune Checkpoint Inhibitors/adverse effects ; }, abstract = {PURPOSE OF REVIEW: Immune checkpoint inhibitor (ICI) therapy revolutionized the treatment of multiple solid and hematologic malignancies. Yet, with it came profound inflammatory toxicities that mimic autoimmune diseases, termed immune-related adverse events (irAEs). Prominent among these is gastrointestinal inflammation, including a spectrum of gastritis, enteritis, and colitis. Here we synthesize an approach to immune checkpoint related enterocolitis (irEC) - including diagnostics and therapeutics - underpinned by new insights into the mechanism behind these phenomena.<br><br>RECENT FINDINGS: This review presents updated insights on how to approach irEC, including novel approaches to selective immunosuppressive therapy, the role of fecal microbiota transplant, and the underlying cellular mechanisms of irEC. This review provides an update on irEC diagnosis and therapy, with considerations of new therapies and special patient populations. The field of gastrointestinal irAEs requires additional investigation, which will ultimately provide the tools required for patients to continue to receive life-saving ICI therapy.}, }
@article {pmid36264385, year = {2023}, author = {Hu, L and Zhao, Y and Liu, S and Zhang, J and You, T and Gan, B and Xu, H}, title = {Lead exposure exacerbates adverse effects of HFD on metabolic function via disruption of gut microbiome, leading to compromised barrier function and inflammation.}, journal = {European journal of nutrition}, volume = {62}, number = {2}, pages = {783-795}, pmid = {36264385}, issn = {1436-6215}, support = {82060606//National Natural Science Foundation of China/ ; }, mesh = {Mice ; Animals ; Diet, High-Fat/adverse effects ; Lead/pharmacology ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Inflammation ; *Metabolic Diseases ; }, abstract = {PURPOSE: The toxicity of lead (Pb) has been intensively studied, while the adverse effects in the population on a high-fat diet (HFD) remain unclear. This study compared the different biologic effects of Pb in CHOW and HFD-fed mice and investigated the important role that gut microbiota may play.<br><br>METHODS: C57BL/6 mice were fed a CHOW diet and HFD with or without 1&#xa0;g/L Pb exposure through drinking water for 8&#xa0;weeks. Using oral glucose tolerance test, histopathological observation, real-time fluorescence quantitative PCR, enzyme-linked immunosorbent assay, and 16S high-throughput sequencing to compare the Pb toxicity, fecal microbiota transplantation was conducted to investigate the key role of gut microbiota.<br><br>RESULTS: The metabolic disorders induced by HFD were aggravated by chronic Pb intake, and HFD exacerbated the Pb accumulation in the colon by 96%, 32% in blood, 27% in the liver, and 142% in tibiae. Concomitantly, Pb induced more serious colonic injury, further disturbing the composition of gut microbiota in the HFD-fed mice. Moreover, altered fecal microbiota by HFD and Pb directly mediated metabolic disorders and colonic damage in recipient mice, which emphasized the importance of gut microbiota.<br><br>CONCLUSION: These findings indicated that the population with HFD has lower resistance and would face more security risks under Pb pollution, and pointed out the importance of assessing the health impacts of food contaminants in people with different dietary patterns.}, }
@article {pmid36264038, year = {2022}, author = {Du, H and Shi, L and Wang, Q and Yan, T and Wang, Y and Zhang, X and Yang, C and Zhao, Y and Yang, X}, title = {Fu Brick Tea Polysaccharides Prevent Obesity via Gut Microbiota-Controlled Promotion of Adipocyte Browning and Thermogenesis.}, journal = {Journal of agricultural and food chemistry}, volume = {70}, number = {43}, pages = {13893-13903}, doi = {10.1021/acs.jafc.2c04888}, pmid = {36264038}, issn = {1520-5118}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Tea/metabolism ; Thermogenesis ; Obesity/metabolism ; Adipose Tissue, Brown/metabolism ; Adipose Tissue, White/metabolism ; Diet, High-Fat ; Mice, Obese ; Adipocytes/metabolism ; Polysaccharides/metabolism ; Mice, Inbred C57BL ; }, abstract = {The antiobesity efficacy and underlying mechanisms of polysaccharides extracted from Fu brick tea (FBTP) were investigated. An 8-week administration of FBTP dose-dependently inhibited increases in body weight and weights of the epididymal-, retroperitoneal- and inguinal-white adipose tissues and stimulated beige-fat development and brown adipose tissue-derived nonshivering thermogenesis in high-fat diet-induced obese mice. FBTP protected against obesity-associated abnormality in serum adiponectin and leptin, indicating its positive regulation of energy metabolism. FBTP reversed gut dysbiosis by enriching beneficial bacteria, for example, Lactobacillus, Parabacteroides, Akkermansia, Bifidobacterium, and Roseburia. Results from the fecal microbiota transplantation further confirmed that FBTP-induced microbial shifts contributed to adipose browning and thermogenesis, thereby alleviating host adiposity, glucose homeostasis, dyslipidemia, and its related hepatic steatosis. Our study demonstrates the great potential of FBTP with prebiotic-like activities in preventing diet-induced obesity and its related metabolic complications via gut microbiota-derived enhancement of fat burning and energy expenditures.}, }
@article {pmid36263410, year = {2022}, author = {Liu, B and Yu, D and Sun, J and Wu, X and Xin, Z and Deng, B and Fan, L and Fu, J and Ge, L and Ren, W}, title = {Characterizing the influence of gut microbiota on host tryptophan metabolism with germ-free pigs.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {11}, number = {}, pages = {190-200}, pmid = {36263410}, issn = {2405-6383}, abstract = {Intestinal microbes are closely associated with host health, depending on metabolic crosstalk between the microbiota and host. Tryptophan metabolism is one of the best examples of metabolic crosstalk between intestinal microbiota and host; however, our understanding about the influence of intestinal microbiota on host tryptophan metabolism is limited. Thus, we established germ-free (GF) pig models to systemically explore the influence of intestinal microbiota on tryptophan metabolism. Five GF pigs were kept in GF conditions throughout the experiment (GF group). Six GF pigs were transplanted with fecal microbiota from donor sows to act as control pigs. Compared with control pigs, the GF pigs had remarkable alterations in tryptophan metabolism. The differential metabolites (P < 0.05) were mainly found in the liver, circulation system and large intestine. Notably, the alteration of metabolites in tryptophan metabolism varied among organs, especially for the serotonin pathway. In GF pigs, tryptophan and kynurenine in the large intestine and 5-hydroxytryptophan in most organs were increased (P < 0.05), while metabolites in the indole pathway in most organs were decreased (P < 0.05). Collectively, our study reveals changes in tryptophan metabolism in GF pigs, highlighting the critical role of gut microbes in shaping host tryptophan metabolism.}, }
@article {pmid36262889, year = {2022}, author = {Zhang, N and Zhang, Y and Wang, Z and Pan, F and Ren, R and Li, Z and Zhao, H and Luo, X and Li, Z and Wang, L and Mo, R and Sun, G and Peng, L and Ni, M and Yang, Y}, title = {Regular fecal microbiota transplantation to Senescence Accelerated Mouse-Prone 8 (SAMP8) mice delayed the aging of locomotor and exploration ability by rejuvenating the gut microbiota.}, journal = {Frontiers in aging neuroscience}, volume = {14}, number = {}, pages = {991157}, pmid = {36262889}, issn = {1663-4365}, abstract = {Recent evidence points out the role of the gut microbiota in the aging process. However, the specific changes and relevant interventions remain unclear. In this study, Senescence Accelerated Mouse-Prone 8 (SAMP8) mice were divided into four groups; young-FMT-group transplanted fecal microbiota from young donors (2-3°months old) and old-FMT-group transplanted from old donors (10-11°months old); additionally, other two groups either adult mice injected with saline solution or untreated mice served as the saline and blank control groups, respectively. All mice were intervened from their 7-months-old until 13-months-old. The open field test at 9 and 11°months of age showed that the mice transplanted with gut microbiota from young donors had significantly better locomotor and exploration ability than those of transplanted with old-donors gut microbiota and those of saline control while was comparable with the blank control. 16S rRNA gene sequencing showed that the gut microbiome of recipient mice of young donors was altered at 11°months of age, whereas the alternation of the gut microbiome of old-donor recipient mice was at 9°months. For comparison, the recipient mice in the blank and saline control groups exhibited changes in the gut microbiome at 10°months of age. The hallmark of aging-related gut microbiome change was an increase in the relative abundance of Akkermansia, which was significantly higher in the recipients transplanted with feces from older donors than younger donors at 9°months of age. This study shows that fecal microbiota transplantation from younger donors can delay aging-related declines in locomotor and exploration ability in mice by changing the gut microbiome.}, }
@article {pmid36261653, year = {2023}, author = {Sophocleous, A and Azfer, A and Huesa, C and Stylianou, E and Ralston, SH}, title = {Probiotics Inhibit Cartilage Damage and Progression of Osteoarthritis in Mice.}, journal = {Calcified tissue international}, volume = {112}, number = {1}, pages = {66-73}, pmid = {36261653}, issn = {1432-0827}, support = {22483/VAC_/Versus Arthritis/United Kingdom ; 22858/VAC_/Versus Arthritis/United Kingdom ; }, mesh = {Mice ; Animals ; *Cartilage, Articular/metabolism ; *Osteoarthritis/metabolism ; Bone and Bones/metabolism ; Knee Joint/pathology ; Disease Models, Animal ; }, abstract = {Increasing interest has focussed on the possible role of alterations in the microbiome in the pathogenesis of metabolic disease, inflammatory disease, and osteoporosis. Here we examined the role of the microbiome in a preclinical model of osteoarthritis in mice subjected to destabilisation of medical meniscus (DMM). The intestinal microbiome was depleted by broad-spectrum antibiotics from 1 week before birth until the age of 6 weeks when mice were subjected reconstitution of the microbiome with faecal microbial transplant (FMT) followed by the administration of a mixture of probiotic strains Lacticaseibacillus paracasei 8700:2, Lactiplantibacillus plantarum HEAL9 and L. plantarum HEAL19 or vehicle. All mice were subjected to DMM at the age of 8 weeks. The severity of osteoarthritis was evaluated by histological analysis and effects on subchondral bone were investigated by microCT analyses. The combination of FMT and probiotics significantly inhibited cartilage damage at the medial femoral condyle such that the OARSI score was 4.64 ± 0.32 (mean ± sem) in the FMT and probiotic group compared with 6.48 ± 0.53 in the FMT and vehicle group (p = 0.007). MicroCT analysis of epiphyseal bone from the femoral condyle showed that the probiotic group had higher BV/TV, increased Tb.Th, and moderately thicker subchondral bone plates than the control group. There was no difference between groups in joint inflammation or in serum concentrations of inflammatory cytokines and chemokines. We conclude that treatment with probiotics following FMT in mice where the microbiome has been depleted inhibits DMM-induced cartilage damage and impacts on the structure of subchondral bone particularly at the femoral condyle. While further studies are required to elucidate the mechanism of action, our research suggests that these probiotics may represent a novel intervention for the treatment of osteoarthritis.}, }
@article {pmid36261423, year = {2022}, author = {Wolstenholme, JT and Saunders, JM and Smith, M and Kang, JD and Hylemon, PB and González-Maeso, J and Fagan, A and Zhao, D and Sikaroodi, M and Herzog, J and Shamsaddini, A and Peña-Rodríguez, M and Su, L and Tai, YL and Zheng, J and Cheng, PC and Sartor, RB and Gillevet, PM and Zhou, H and Bajaj, JS}, title = {Reduced alcohol preference and intake after fecal transplant in patients with alcohol use disorder is transmissible to germ-free mice.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6198}, pmid = {36261423}, issn = {2041-1723}, support = {P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; I01 CX001076/CX/CSRD VA/United States ; P50 AA022537/AA/NIAAA NIH HHS/United States ; R01 MH084894/MH/NIMH NIH HHS/United States ; F30 MH116550/MH/NIMH NIH HHS/United States ; I01 BX004033/BX/BLRD VA/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; R21 TR003095/TR/NCATS NIH HHS/United States ; P01 DK094779/DK/NIDDK NIH HHS/United States ; R21 AA026629/AA/NIAAA NIH HHS/United States ; IK6 BX004477/BX/BLRD VA/United States ; R01 MH111940/MH/NIMH NIH HHS/United States ; R01 AA026347/AA/NIAAA NIH HHS/United States ; R01 DK104893/DK/NIDDK NIH HHS/United States ; R01 DK057543/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; Male ; *Fecal Microbiota Transplantation ; *Alcoholism/therapy ; Mice, Inbred C57BL ; Alcohol Drinking ; Ethanol ; }, abstract = {Alcohol use disorder is a major cause of morbidity, which requires newer treatment approaches. We previously showed in a randomized clinical trial that alcohol craving and consumption reduces after fecal transplantation. Here, to determine if this could be transmitted through microbial transfer, germ-free male C57BL/6 mice received stool or sterile supernatants collected from the trial participants pre-/post-fecal transplant. We found that mice colonized with post-fecal transplant stool but not supernatants reduced ethanol acceptance, intake and preference versus pre-fecal transplant colonized mice. Microbial taxa that were higher in post-fecal transplant humans were also associated with lower murine alcohol intake and preference. A majority of the differentially expressed genes (immune response, inflammation, oxidative stress response, and epithelial cell proliferation) occurred in the intestine rather than the liver and prefrontal cortex. These findings suggest a potential for therapeutically targeting gut microbiota and the microbial-intestinal interface to alter gut-liver-brain axis and reduce alcohol consumption in humans.}, }
@article {pmid36259455, year = {2023}, author = {Celorrio, M and Shumilov, K and Rodgers, R and Schriefer, L and Li, Y and Baldridge, MT and Friess, SH}, title = {Innate and Peripheral Immune Alterations after Traumatic Brain Injury Are Regulated in a Gut Microbiota-Dependent Manner in Mice.}, journal = {Journal of neurotrauma}, volume = {40}, number = {7-8}, pages = {772-787}, pmid = {36259455}, issn = {1557-9042}, support = {R01 NS097721/NS/NINDS NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Neuroinflammatory Diseases ; Anti-Bacterial Agents/pharmacology ; Metronidazole ; *Brain Injuries, Traumatic/therapy ; Ampicillin ; Mice, Inbred C57BL ; }, abstract = {Traumatic brain injury (TBI) patients are at high risk for disruption of the gut microbiome. Previously, we have demonstrated that broad-spectrum antibiotic exposure after TBI drastically alters the gut microbiota and modulates neuroinflammation, neurogenesis, and long-term fear memory. However, these data did not determine if the impact of antibiotic exposure on the brain's response to injury was mediated directly by antibiotics or indirectly via modulation of the gut microbiota. We designed two different approaches to address this knowledge gap. One was utilizing fecal microbiota transplantation (FMT) from control and antibiotic-treated mice (treated with vancomycin, neomycin, ampicillin, and metronidazole [VNAM]) into germ-free (GF) mice prior to injury, and the other was exposing specific pathogen-free (SPF) mice to a 2-week period of antibiotics prior to injury but discontinuing antibiotics 72 h prior to injury. GF mice receiving FMT from VNAM-treated mice (GF-VNAM) demonstrated reduced gut bacterial alpha diversity and richness compared with GF mice receiving control FMT. At 7 days post-injury, GF-VNAM had increased microglial activation, reduced infiltration of T cells, and decreased neurogenesis. Similarly, SPF mice exposed to antibiotics prior to but not after injury demonstrated similar alterations in neuroinflammation and neurogenesis compared with control mice. These data support our hypothesis implicating the gut microbiota as an important modulator of the neuroinflammatory process and neurogenesis after TBI and provide an exciting new approach for neuroprotective therapeutics for TBI.}, }
@article {pmid36257564, year = {2022}, author = {Li, P and Ma, X and Liu, D and Wei, Y and Li, P and Hou, H and Yao, J and Chen, A and Liang, Y and Zhou, Z and Wang, P}, title = {A microbiome abundant environment remodels the intestinal microbiota and improves resistance to obesity induced by chlorpyrifos in mice.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {315}, number = {}, pages = {120415}, doi = {10.1016/j.envpol.2022.120415}, pmid = {36257564}, issn = {1873-6424}, mesh = {Animals ; Mice ; Humans ; *Chlorpyrifos/toxicity ; *Gastrointestinal Microbiome ; Ecosystem ; Obesity ; Intestines ; Mice, Inbred C57BL ; }, abstract = {There is a growing consensus that the appropriate microbiome abundant environment actuates microbiota changes to influence human health. Whether living environment reacts on the threat of contaminants and the underlying mechanism remain largely unknown. Therefore, we constructed microbiome abundant environment models, focusing on their regulatory effects on the obesity induced by the exogenous chemical chlorpyrifos (CPF) and the related mechanisms. The results uncovered that the constructed farm and woodland microbiome abundant environment could protect mice against CPF-induced obesity effectively. The microbiome abundant environment regulated CPF-induced microbiota imbalance, characterized by an increase in Lactobacillus abundance. These altered microbiotas modified the intestinal immune system by increasing the expression of Foxp3 and IL-10, and mitigated intestinal barrier injury by upregulating the expression of IL-22 and intestinal tight junction proteins. Fecal microbiota transplantation could receive similar phenotypes on alleviating CPF-induced obesity development. Our results demonstrate that the microbiome abundant environment attenuates exogenous chemical-induced health risks by remodeling the intestinal microbiota, improving the intestinal ecosystem, and preventing intestinal epithelial leakage.}, }
@article {pmid36256653, year = {2022}, author = {Collier, AJ and Gomez, DE and Monteith, G and Plattner, BL and Verbrugghe, A and Webb, J and Weese, JS and Blois, SL}, title = {Investigating fecal microbial transplant as a novel therapy in dogs with inflammatory bowel disease: A preliminary study.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0276295}, pmid = {36256653}, issn = {1932-6203}, mesh = {Dogs ; Animals ; Fecal Microbiota Transplantation/methods ; *Inflammatory Bowel Diseases/therapy/veterinary/etiology ; Feces ; *Microbiota ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: There are limited studies investigating the use of fecal microbial transplant (FMT) in dogs with inflammatory bowel disease (IBD). The aim of this preliminary study was to assess the feasibility of adding FMT to standard therapy (corticosteroids and a hypoallergenic diet) for dogs with IBD and to and to describe the changes in measured outcomes after 30 days of treatment.<br><br>METHODS: Thirteen client-owned dogs with IBD were enrolled in this double blinded, randomized clinical trial. All dogs received corticosteroid therapy and a hypoallergenic diet; dogs were randomized to receive either placebo or FMT. Measured outcomes included the canine chronic enteropathy clinical activity index (CCECAI) at 1 week and 1 month after enrolment. Fecal microbiota were analyzed after extracting DNA from fecal samples and profiling using 16S amplicon sequencing. Dogs in the placebo group not responding to treatment after 1 month were offered FMT.<br><br>RESULTS: The CCECAI significantly decreased over time in both groups (p = 0.001). There were no significant differences between the CCECAI of the placebo and FMT group at each time point (F test from ANOVA, p = 0.40). No adverse effects were reported in the 30 days following FMT.<br><br>CONCLUSIONS: The addition of FMT to standard therapy for IBD was feasible. No significant differences were observed in the CCECAI between groups at each time point. Large scale clinical trials can be performed using these methods to evaluate the longer term effect of FMT on clinical signs, microbial diversity, and other outcomes.}, }
@article {pmid36256625, year = {2022}, author = {Davis, BT and Chen, Z and Islam, MBAR and Timken, ME and Procissi, D and Schwulst, SJ}, title = {POSTINJURY FECAL MICROBIOME TRANSPLANT DECREASES LESION SIZE AND NEUROINFLAMMATION IN TRAUMATIC BRAIN INJURY.}, journal = {Shock (Augusta, Ga.)}, volume = {58}, number = {4}, pages = {287-294}, pmid = {36256625}, issn = {1540-0514}, support = {R01 GM130662/GM/NIGMS NIH HHS/United States ; R01 NS127865/NS/NINDS NIH HHS/United States ; R21 NS116638/NS/NINDS NIH HHS/United States ; }, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation ; Neuroinflammatory Diseases ; *Neurodegenerative Diseases/complications/metabolism ; *Brain Injuries, Traumatic/microbiology ; Mice, Inbred C57BL ; Microglia/metabolism ; *Microbiota ; Chromium/metabolism ; }, abstract = {Background: Traumatic brain injury (TBI) is an underrecognized public health threat. The constitutive activation of microglia after TBI has been linked to long-term neurocognitive deficits and the progression of neurodegenerative disease. Evolving evidence indicates a critical role for the gut-brain axis in this process. Specifically, TBI has been shown to induce the depletion of commensal gut bacteria. The resulting gut dysbiosis is associated with neuroinflammation and disease. Hypothesis: We hypothesized that fecal microbiota transplantation would attenuate microglial activation and improve neuropathology after TBI. Methods: C57Bl/6 mice were subjected to severe TBI (n = 10) or sham injury (n = 10) via an open-head controlled cortical impact. The mice underwent fecal microbiota transplantation (FMT) or vehicle alone via oral gavage once weekly for 4 weeks after injury. At 59 days after TBI, mice underwent three-dimensional, contrast-enhanced magnetic resonance imaging. Following imaging, mice were killed, brains harvested at 60 DPI, and CD45+ cells isolated via florescence-activated cell sorting. cDNA libraries were prepared using the 10x Genomics Chromium Single Cell 3' Reagent kit followed by sequencing on a HiSeq4000 instrument, and computational analysis was performed. Results: Fecal microbiota transplantation resulted in a >marked reduction of ventriculomegaly (P < 0.002) and preservation of white matter connectivity at 59 days after TBI (P < 0.0001). In addition, microglia from FMT-treated mice significantly reduced inflammatory gene expression and enriched pathways involving the heat-shock response compared with mice treated with vehicle alone. Conclusions: We hypothesized that restoring gut microbial community structure via FMT would attenuate microglial activation and reduce neuropathology after TBI. Our data demonstrated significant preservation of cortical volume and white matter connectivity after an injury compared with mice treated with vehicle alone. This preservation of neuroanatomy after TBI was associated with a marked reduction in inflammatory gene expression within the microglia of FMT-treated mice. Microglia from FMT-treated mice enriched pathways in the heat-shock response, which is known to play a neuroprotective role in TBI and other neurodegenerative disease processes.}, }
@article {pmid36255205, year = {2022}, author = {Hu, B and Das, P and Lv, X and Shi, M and Aa, J and Wang, K and Duan, L and Gilbert, JA and Nie, Y and Wu, XL}, title = {Erratum for Hu et al., "Effects of 'Healthy' Fecal Microbiota Transplantation against the Deterioration of Depression in Fawn-Hooded Rats".}, journal = {mSystems}, volume = {7}, number = {6}, pages = {e0095322}, doi = {10.1128/msystems.00953-22}, pmid = {36255205}, issn = {2379-5077}, }
@article {pmid36254996, year = {2023}, author = {Kang, JN and Sun, ZF and Li, XY and Zhang, XD and Jin, ZX and Zhang, C and Zhang, Y and Wang, HY and Huang, NN and Jiang, JH and Ning, B}, title = {Alterations in gut microbiota are related to metabolite profiles in spinal cord injury.}, journal = {Neural regeneration research}, volume = {18}, number = {5}, pages = {1076-1083}, pmid = {36254996}, issn = {1673-5374}, abstract = {Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8-T10 traumatic spinal cord injury. We used 16S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids (L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.}, }
@article {pmid36253536, year = {2022}, author = {Fernandes, MR and Aggarwal, P and Costa, RGF and Cole, AM and Trinchieri, G}, title = {Targeting the gut microbiota for cancer therapy.}, journal = {Nature reviews. Cancer}, volume = {22}, number = {12}, pages = {703-722}, pmid = {36253536}, issn = {1474-1768}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Immunotherapy/methods ; Fecal Microbiota Transplantation/methods ; *Neoplasms/drug therapy ; *Microbiota ; }, abstract = {Growing evidence suggests that the gut microbiota modulates the efficacy and toxicity of cancer therapy, most notably immunotherapy and its immune-related adverse effects. The poor response to immunotherapy in patients treated with antibiotics supports this influential role of the microbiota. Until recently, results pertaining to the identification of the microbial species responsible for these effects were incongruent, and relatively few studies analysed the underlying mechanisms. A better understanding of the taxonomy of the species involved and of the mechanisms of action has since been achieved. Defined bacterial species have been shown to promote an improved response to immune-checkpoint inhibitors by producing different products or metabolites. However, a suppressive effect of Gram-negative bacteria may be dominant in some unresponsive patients. Machine learning approaches trained on the microbiota composition of patients can predict the ability of patients to respond to immunotherapy with some accuracy. Thus, interest in modulating the microbiota composition to improve patient responsiveness to therapy has been mounting. Clinical proof-of-concept studies have demonstrated that faecal microbiota transplantation or dietary interventions might be utilized clinically to improve the success rate of immunotherapy in patients with cancer. Here, we review recent advances and discuss emerging strategies for microbiota-based cancer therapies.}, }
@article {pmid36253108, year = {2022}, author = {Zhu, T and Wang, Z and He, J and Zhang, X and Zhu, C and Zhang, S and Li, Y and Fan, S}, title = {D-galactose protects the intestine from ionizing radiation-induced injury by altering the gut microbiome.}, journal = {Journal of radiation research}, volume = {63}, number = {6}, pages = {805-816}, pmid = {36253108}, issn = {1349-9157}, support = {332019098//Fundamental Research Funds for the Central Universities/ ; 81730086//National Natural Science Foundation of China/ ; 2018072-DZ-02//&#xff0c;CAMS Innovation Fund for Medical Sciences/ ; }, mesh = {Male ; Mice ; Animals ; *Galactose ; Mice, Inbred C57BL ; Radiation, Ionizing ; *Radiation Injuries ; }, abstract = {This article aims to investigate the protection of the intestine from ionizing radiation-induced injury by using D-galactose (D-gal) to alter the gut microbiome. In addition, this observation opens up further lines of research to further increase therapeutic potentials. Male C57BL/6 mice were exposed to 7.5 Gy of total body irradiation (TBI) or 13 Gy of total abdominal irradiation (TAI) in this study. After adjustment, D-gal was intraperitoneally injected into mice at a dose of 750 mg/kg/day. Survival rates, body weights, histological experiments and the level of the inflammatory factor IL-1β were observed after TBI to investigate radiation injury in mice. Feces were collected from mice for 16S high-throughput sequencing after TAI. Furthermore, fecal microorganism transplantation (FMT) was performed to confirm the effect of D-gal on radiation injury recovery. Intraperitoneally administered D-gal significantly increased the survival of irradiated mice by altering the gut microbiota structure. Furthermore, the fecal microbiota transplanted from D-gal-treated mice protected against radiation injury and improved the survival rate of recipient mice. Taken together, D-gal accelerates gut recovery following radiation injury by promoting the growth of specific microorganisms, especially those in the class Erysipelotrichia. The study discovered that D-gal-induced changes in the microbiota protect against radiation-induced intestinal injury. Erysipelotrichia and its metabolites are a promising therapeutic option for post-radiation intestinal regeneration.}, }
@article {pmid36252894, year = {2022}, author = {Li, D and Cui, L and Gao, Y and Li, Y and Tan, X and Xu, H}, title = {Fecal microbiota transplantation improves intestinal inflammation in mice with ulcerative colitis by modulating intestinal flora composition and down-regulating NF-kB signaling pathway.}, journal = {Microbial pathogenesis}, volume = {173}, number = {Pt A}, pages = {105803}, doi = {10.1016/j.micpath.2022.105803}, pmid = {36252894}, issn = {1096-1208}, mesh = {Animals ; Mice ; *Colitis, Ulcerative/chemically induced/therapy ; Colon/pathology ; Dextran Sulfate ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Inflammation/therapy/pathology ; Interleukin-6 ; Mice, Inbred C57BL ; NF-kappa B ; Signal Transduction ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine. It is characterized with recurrent. The pathogenesis is mainly associated with environmental factors, genetic susceptibility, dysbiosis of the intestinal flora and autoimmunity. The role of intestinal flora disorders in the pathogenesis and progression of UC is becoming increasingly prominent. More and more studies have confirmed that fecal microbiota transplantation (FMT) could reshape the composition of UC intestinal flora and it is expected to be a new strategy for UC treatment. In this study, we used 2% Dextran sulfate sodium (DSS) for 7 days to induce acute colitis model in mice, and interfere with FMT and Enterotoxigenic Escherichia coli (ETEC). ELISA and immunohistochemistry were applied to detect the concentration and expression of NF-κB p65, STAT3 and IL-6. 16SrRNA high-throughput sequencing was performed to explore the composition of intestinal flora. The aim was to study the treatment effect of FMT on UC mice and explore its potential mechanism by observing the changes of intestinal flora composition and diversity, and its relationship with NF-κB p65, STAT3 and IL-6 expression. We conclude that FMT could improve intestinal flora disorder in mice with ulcerative colitis, regulate NF-κB signaling pathway, and significantly reduce intestinal inflammation in UC mice.}, }
@article {pmid36250045, year = {2022}, author = {Lv, L and Ruan, G and Ping, Y and Cheng, Y and Tian, Y and Xiao, Z and Zhao, X and Chen, D and Wei, Y}, title = {Clinical study on sequential treatment of severe diarrhea irritable bowel syndrome with precision probiotic strains transplantation capsules, fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1025889}, pmid = {36250045}, issn = {2235-2988}, mesh = {Abdominal Pain ; Bacillus subtilis ; Diarrhea/therapy ; *Enterococcus faecium ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome/therapy ; *Probiotics/therapeutic use ; Quality of Life ; Treatment Outcome ; }, abstract = {OBJECTIVE: To study the effect of precision probiotic strains transplantation capsules on diarrhea irritable bowel syndrome compared with fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules.<br><br>METHODS: Two patients with severe irritable bowel syndrome were treated with precision probiotic strains transplantation capsules, fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules in sequence. IBS-SSS, IBS-QoL, GSRS, stool frequency, stool character, degree of abdominal pain, GAD-7, and PHQ9 scores of patients at 0, 2, 4, 6, 8, 10, and 12 weeks of treatment were monitored and recorded, and stool samples were collected for metagenomics and metabolomics.<br><br>RESULTS: It was found that the IBS-SSS score of patient case 1 decreased by 175 points and that of patient case 2 decreased by 100 points after treatment of precision probiotic strains transplantation capsules. There was no significant decrease after fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules were used. At the same time, compared with fecal microbiota transplantation and live combined bacillus subtilis and enterococcus faecium capsules, the IBS QoL, stool frequency, stool character, degree of abdominal pain and GAD-7 score of patient case 1 improved more significantly by the precision probiotic strains transplantation capsules. And the stool frequency and stool character score of patient case 2 decreased more significantly. Intestinal microbiota also improved more significantly after the precise capsule transplantation treatment. And we found Eubacterium_ Eligens showed the same change trend in the treatment of two patients, which may play a role in the treatment.<br><br>CONCLUSION: precision probiotic strains transplantation capsules is more beneficial to improve the intestinal microbiota of patients than microbiota transplantation capsule and live combined bacillus subtilis and enterococcus faecium capsules, so as to better alleviate clinical symptoms. This study provides a more perfect and convenient therapeutic drugs for the treatment of IBS.}, }
@article {pmid36249307, year = {2022}, author = {Owais, R and Iqbal, M}, title = {Monkeypox and fecal microbiota for transplantation(FMT): An unprecedented risk?.}, journal = {Annals of medicine and surgery (2012)}, volume = {82}, number = {}, pages = {104779}, pmid = {36249307}, issn = {2049-0801}, }
@article {pmid36248877, year = {2022}, author = {Zeng, L and Deng, Y and Yang, K and Chen, J and He, Q and Chen, H}, title = {Safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases: A systematic review and meta-analysis.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {944387}, pmid = {36248877}, issn = {1664-3224}, mesh = {*Autoimmune Diseases/etiology/therapy ; C-Peptide ; Child ; *Colitis, Ulcerative/therapy ; *Crohn Disease/etiology ; Fecal Microbiota Transplantation/adverse effects/methods ; *Hereditary Autoinflammatory Diseases/etiology ; Humans ; }, abstract = {OBJECTIVE: To evaluate the safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases.<br><br>METHODS: Relevant literature was retrieved from the PubMed database, Embase database, Cochrane Library database, etc. The search period is from the establishment of the database to January 2022. The outcomes include clinical symptoms, improvement in biochemistry, improvement in intestinal microbiota, improvement in the immune system, and adverse events. Literature screening and data extraction were independently carried out by two researchers according to the inclusion and exclusion criteria, and RevMan 5.3 software was used for statistics and analysis.<br><br>RESULTS: Overall, a total of 14 randomized controlled trials (RCTs) involving six types of autoimmune diseases were included. The results showed the following. 1) Type 1 diabetes mellitus (T1DM): compared with the autologous fecal microbiota transplantation (FMT) group (control group), the fasting plasma C peptide in the allogenic FMT group at 12 months was lower. 2) Systemic sclerosis: at week 4, compared with one of two placebo controls, three patients in the experimental group reported a major improvement in fecal incontinence. 3) Ulcerative colitis, pediatric ulcerative colitis, and Crohn's disease: FMT may increase clinical remission, clinical response, and endoscopic remission for patients with ulcerative colitis and increase clinical remission for patients with Crohn's disease. 4) Psoriatic arthritis: there was no difference in the ratio of ACR20 between the two groups.<br><br>CONCLUSION: Based on current evidence, the application of FMT in the treatment of autoimmune diseases is effective and relatively safe, and it is expected to be used as a method to induce remission of active autoimmune diseases.<br><br>https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235055, identifier CRD42021235055.}, }
@article {pmid36247756, year = {2022}, author = {Barlow, B and Ponnaluri, S and Barlow, A and Roth, W}, title = {Targeting the gut microbiome in the management of sepsis-associated encephalopathy.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {999035}, pmid = {36247756}, issn = {1664-2295}, abstract = {Brain injury resulting from sepsis, or sepsis-associated encephalopathy (SAE), occurs due to impaired end-organ perfusion, dysregulated inflammation affecting the central nervous system (CNS), blood-brain barrier (BBB) disruption, mitochondrial dysfunction, oxidative stress, accumulation of toxic neuropeptides and impaired toxin clearance secondary to sepsis-induced hepatic and renal dysfunction. The gut microbiome becomes pathologically altered in sepsis, which likely contributes to the pathogenesis of SAE. Herein, we review the literature detailing dysregulation of microbiota-gut-brain axis (MGBA) in SAE and highlight potential therapeutic strategies to modulate the gut microbiome to mitigate sepsis-induced brain injury.}, }
@article {pmid36246150, year = {2021}, author = {Li, H and Fu, ZY and Arslan, ME and Cho, D and Lee, H}, title = {Differential diagnosis and management of immune checkpoint inhibitor-induced colitis: A comprehensive review.}, journal = {World journal of experimental medicine}, volume = {11}, number = {6}, pages = {79-92}, pmid = {36246150}, issn = {2220-315X}, abstract = {Immune checkpoint inhibitors (ICIs) are a new class of cancer pharmacotherapy consisting of antibodies that block inhibitory immune regulators such as cytotoxic T lymphocyte antigen 4, programmed cell death 1 and programmed death-ligand 1. Checkpoint blockade by ICIs reactivates a tumor-specific T cell response. Immune-related adverse events can occur in various organs including skin, liver, and gastrointestinal tract. Mild to severe colitis is the most common side effect with some experiencing rapid progression to more serious complications including bowel perforation and even death. Prompt diagnosis and management of ICI-induced colitis is crucial for optimal outcome. Unfortunately, its clinical, endoscopic and histopathologic presentations are non-specific and overlap with those of colitis caused by other etiologies, such as infection, medication, graft-versus-host disease and inflammatory bowel disease. Thus, a definitive diagnosis can only be rendered after these other possible etiologies are excluded. Sometimes an extensive clinical, laboratory and radiologic workup is required, making it challenging to arrive at a prompt diagnosis. Most patients experience full resolution of symptoms with corticosteroids and/or infliximab. For ICI-induced colitis that is treatment-refractory, small scale studies offer alternative strategies, such as vedolizumab and fecal microbiota transplantation. In this review, we focus on the clinical features, differential diagnosis, and management of ICI-induced colitis with special attention to emerging treatment options for treatment-refractory ICI-induced colitis.}, }
@article {pmid36246106, year = {2022}, author = {Dardi, P and Dos Santos-Eichler, RA and de Oliveira, S and Vinolo, MAR and Câmara, NOS and Rossoni, LV}, title = {Reduced intestinal butyrate availability is associated with the vascular remodeling in resistance arteries of hypertensive rats.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {998362}, pmid = {36246106}, issn = {1664-042X}, abstract = {During hypertension an unbalance of short-chain fatty acids (SCFAs) production by intestinal bacteria is described. However, no data evaluate the association of SCFAs and vascular remodeling in hypertension, which is an important hallmark of this disease. Thus, the present study aims to evaluate the correlations between SCFAs availability and the resistance arteries remodeling in hypertension, as well as to identify the possible pathway by which the SCFAs could exert a structural and mechanical influence. Hence, male spontaneously hypertensive rats (SHR) and normotensive Wistar rats had blood pressure measured by tail-cuff plethysmography; fecal SCFAs content assessed by gas chromatography; gene expression of SCFAs-transporters in gut epithelium and SCFAs-sensing receptors on mesenteric resistance arteries (MRA) quantified by PCR; and MRA structural and mechanical parameters analyzed by pressure myograph. Reduced butyrate fecal content was found in SHR, with no changes in propionate and acetate, as well as decreased mRNA levels of SCFAs-transporters (MCT1, MCT4, and SMCT1) in the intestinal epithelium. In addition, lower gene expression of SCFAs-sensing receptors (GPR41, GPR43, and GPR109a, but not Olfr78) was identified in MRAs of SHR, which also shows inward eutrophic remodeling with stiffness. Butyrate content presented a negative correlation with systolic blood pressure and with the structural alterations found on MRAs, while a positive correlation between butyrate content and mechanical parameters was detected. Altogether the present study suggests that lower butyrate content due to ineffective SCFA bioavailability, associated with lower SCFAs-sensing receptors expression, could favor MRA remodeling, increasing peripheral vascular resistance and worsening hypertension prognosis.}, }
@article {pmid36239349, year = {2022}, author = {Ni, Y and Zheng, L and Nan, S and Ke, L and Fu, Z and Jin, J}, title = {Enterorenal crosstalks in diabetic nephropathy and novel therapeutics targeting the gut microbiota.}, journal = {Acta biochimica et biophysica Sinica}, volume = {54}, number = {10}, pages = {1406-1420}, pmid = {36239349}, issn = {1745-7270}, mesh = {Humans ; *Diabetic Nephropathies/drug therapy ; *Gastrointestinal Microbiome ; Kidney ; *Dipeptidyl-Peptidase IV Inhibitors/pharmacology/therapeutic use ; *Probiotics/therapeutic use ; *Diabetes Mellitus ; }, abstract = {The role of gut-kidney crosstalk in the progression of diabetic nephropathy (DN) is receiving increasing concern. On one hand, the decline in renal function increases circulating uremic toxins and affects the composition and function of gut microbiota. On the other hand, intestinal dysbiosis destroys the epithelial barrier, leading to increased exposure to endotoxins, thereby exacerbating kidney damage by inducing systemic inflammation. Dietary inventions, such as higher fiber intake, prebiotics, probiotics, postbiotics, fecal microbial transplantation (FMT), and engineering bacteria and phages, are potential microbiota-based therapies for DN. Furthermore, novel diabetic agents, such as glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, may affect the progression of DN partly through gut microbiota. In the current review, we mainly summarize the evidence concerning the gut-kidney axis in the advancement of DN and discuss therapies targeting the gut microbiota, expecting to provide new insight into the clinical treatment of DN.}, }
@article {pmid36239189, year = {2023}, author = {Ghorbani, Y and Schwenger, KJP and Sharma, D and Jung, H and Yadav, J and Xu, W and Lou, W and Poutanen, S and Hota, SS and Comelli, EM and Philpott, D and Jackson, TD and Okrainec, A and Gaisano, HY and Allard, JP}, title = {Effect of faecal microbial transplant via colonoscopy in patients with severe obesity and insulin resistance: A randomized double-blind, placebo-controlled Phase 2 trial.}, journal = {Diabetes, obesity &amp; metabolism}, volume = {25}, number = {2}, pages = {479-490}, doi = {10.1111/dom.14891}, pmid = {36239189}, issn = {1463-1326}, support = {TB2-138775//CIHR/Canada ; }, mesh = {Humans ; *Insulin Resistance ; *Obesity, Morbid ; Quality of Life ; Obesity/complications/therapy ; Colonoscopy ; Double-Blind Method ; }, abstract = {AIM: To assess the effects of faecal microbial transplant (FMT) from lean people to subjects with obesity via colonoscopy.<br><br>MATERIAL AND METHODS: In a double-blind, randomized controlled trial, subjects with a body mass index &#x2265;&#x2009;35&#x2009;kg/m[2] and insulin resistance were randomized, in a 1:1 ratio in blocks of four, to either allogenic (from healthy lean donor; n&#xa0;=&#xa0;15) or autologous FMT (their own stool; n&#xa0;=&#xa0;13) delivered in the caecum and were followed for 3&#xa0;months. The main outcome was homeostatic model assessment of insulin resistance (HOMA-IR) and secondary outcomes were glycated haemoglobin levels, lipid profile, weight, gut hormones, endotoxin, appetite measures, intestinal microbiome (IM), metagenome, serum/faecal metabolites, quality of life, anxiety and depression scores.<br><br>RESULTS: In the allogenic versus autologous groups, HOMA-IR and clinical variables did not change significantly, but IM and metabolites changed favourably (P&#xa0;<&#x2009;0.05): at 1 month, Coprococcus, Bifidobacterium, Bacteroides and Roseburia increased, and Streptococcus decreased; at 3 months, Bacteroides and Blautia increased. Several species also changed significantly. For metabolites, at 1 month, serum kynurenine decreased and faecal indole acetic acid and butenylcarnitine increased, while at 3 months, serum isoleucine, leucine, decenoylcarnitine and faecal phenylacetic acid decreased. Metagenomic pathway representations and network analyses assessing relationships with clinical variables, metabolites and IM were significantly enhanced in the allogenic versus autologous groups. LDL and appetite measures improved in the allogenic (P&#xa0;<&#x2009;0.05) but not in the autologous group.<br><br>CONCLUSIONS: Overall, in those with obeisty, allogenic FMT via colonoscopy induced favourable changes in IM, metabolites, pathway representations and networks even though other metabolic variables did not change. LDL and appetite variables may also benefit.}, }
@article {pmid36237764, year = {2022}, author = {Jayasinghe, M and Prathiraja, O and Kayani, AMA and Jena, R and Caldera, D and Silva, MS and Singhal, M and Pierre, J}, title = {The Role of Diet and Gut Microbiome in Multiple Sclerosis.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e28975}, pmid = {36237764}, issn = {2168-8184}, abstract = {Multiple sclerosis (MS) is a chronic demyelinating condition of the central nervous system (CNS) characterized by immune-mediated damage to the myelin sheath of nerve cells. Genetic and environmental factors are believed to play a significant role. Unfortunately, the knowledge of therapeutic modalities in MS remains very limited, necessitating the need for novel therapeutic strategies. In the previous decade, there has been an influx of studies on the gut microbiome and its link to various neurological conditions, including MS. Various diets may have favorable effects on the gut microflora and may significantly alter the progression and outcomes of MS. Thus, identifying the merits of various diets and modulating them according to the specific nutritional requirements of MS patients can go a long way toward slowing the progression of the disease. Nutritional interventions and the use of the gut microbiome as diagnostic and therapeutic modalities open a host of new possibilities regarding the disease. In this review, we investigate the role of diet and the gut microbiome in the progression of MS. The functions of the gut-brain axis, antioxidants, vitamins, obesity, and various diets are also covered in this article.}, }
@article {pmid36233289, year = {2022}, author = {Guardamagna, M and Berciano-Guerrero, MA and Villaescusa-González, B and Perez-Ruiz, E and Oliver, J and Lavado-Valenzuela, R and Rueda-Dominguez, A and Barragán, I and Queipo-Ortuño, MI}, title = {Gut Microbiota and Therapy in Metastatic Melanoma: Focus on MAPK Pathway Inhibition.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36233289}, issn = {1422-0067}, support = {MA-37938-2018//Novartis (Spain)/ ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy ; *Melanoma/drug therapy ; Mitogen-Activated Protein Kinase Kinases ; *Neoplasms, Second Primary/drug therapy ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Proto-Oncogene Proteins B-raf/genetics ; Tumor Microenvironment ; }, abstract = {Gut microbiome (GM) and its either pro-tumorigenic or anti-tumorigenic role is intriguing and constitutes an evolving landscape in translational oncology. It has been suggested that these microorganisms may be involved in carcinogenesis, cancer treatment response and resistance, as well as predisposition to adverse effects. In melanoma patients, one of the most immunogenic cancers, immune checkpoint inhibitors (ICI) and MAPK-targeted therapy-BRAF/MEK inhibitors-have revolutionized prognosis, and the study of the microbiome as a modulating factor is thus appealing. Although BRAF/MEK inhibitors constitute one of the main backbones of treatment in melanoma, little is known about their impact on GM and how this might correlate with immune re-induction. On the contrary, ICI and their relationship to GM has become an interesting field of research due to the already-known impact of immunotherapy in modulating the immune system. Immune reprogramming in the tumor microenvironment has been established as one of the main targets of microbiome, since it can induce immunosuppressive phenotypes, promote inflammatory responses or conduct anti-tumor responses. As a result, ongoing clinical trials are evaluating the role of fecal microbiota transplant (FMT), as well as the impact of using dietary supplements, antibiotics and probiotics in the prediction of response to therapy. In this review, we provide an overview of GM's link to cancer, its relationship with the immune system and how this may impact response to treatments in melanoma patients. We also discuss insights about novel therapeutic approaches including FMT, changes in diet and use of probiotics, prebiotics and symbiotics. Finally, we hypothesize on the possible pathways through which GM may impact anti-tumor efficacy in melanoma patients treated with targeted therapy, an appealing subject of which little is known.}, }
@article {pmid36232336, year = {2022}, author = {Huynh, QS and Elangovan, S and Holsinger, RMD}, title = {Non-Pharmacological Therapeutic Options for the Treatment of Alzheimer's Disease.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232336}, issn = {1422-0067}, mesh = {*Alzheimer Disease/metabolism ; Humans ; }, abstract = {Alzheimer's disease is a growing global crisis in need of urgent diagnostic and therapeutic strategies. The current treatment strategy mostly involves immunotherapeutic medications that have had little success in halting disease progress. Hypotheses for pathogenesis and development of AD have been expanded to implicate both organ systems as well as cellular reactions. Non-pharmacologic interventions ranging from minimally to deeply invasive have attempted to address these diverse contributors to AD. In this review, we aim to delineate mechanisms underlying such interventions while attempting to provide explanatory links between the observed differences in disease states and postulated metabolic or structural mechanisms of change. The techniques discussed are not an exhaustive list of non-pharmacological interventions against AD but provide a foundation to facilitate a deeper understanding of the area of study.}, }
@article {pmid36230772, year = {2022}, author = {Bawaneh, A and Wilson, AS and Levi, N and Howard-McNatt, MM and Chiba, A and Soto-Pantoja, DR and Cook, KL}, title = {Intestinal Microbiota Influence Doxorubicin Responsiveness in Triple-Negative Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {19}, pages = {}, pmid = {36230772}, issn = {2072-6694}, support = {P30 CA012197/CA/NCI NIH HHS/United States ; P30CA012197/NH/NIH HHS/United States ; CCR18547795//Susan G. Komen Breast Cancer Foundation/ ; }, abstract = {Triple-negative breast cancer (TNBC) is highly aggressive with a poor 5-year survival rate. Targeted therapy options are limited and most TNBC patients are treated with chemotherapy. This study aimed to determine whether doxorubicin (Dox) shifts the gut microbiome and whether gut microbiome populations influence chemotherapeutic responsiveness. Female BALB/c mice (n = 115) were injected with 4T1-luciferase cells (a murine syngeneic TNBC model) and treated with Dox and/or antibiotics, high-fat diet-derived fecal microbiota transplant (HFD-FMT), or exogenous lipopolysaccharide (LPS). Metagenomic sequencing was performed on fecal DNA samples. Mice that received Dox were stratified into Dox responders or Dox nonresponders. Mice from the Dox responders and antibiotics + Dox groups displayed reduced tumor weight and metastatic burden. Metagenomic analysis showed that Dox was associated with increased Akkermansia muciniphila proportional abundance. Moreover, Dox responders showed an elevated proportional abundance of Akkermansia muciniphila prior to Dox treatment. HFD-FMT potentiated tumor growth and decreased Dox responsiveness. Indeed, lipopolysaccharide, a structural component of Gram-negative bacteria, was increased in the plasma of Dox nonresponders and FMT + Dox mice. Treatment with exogenous LPS increases intestinal inflammation, reduces Dox responsiveness, and increases lung metastasis. Taken together, we show that modulating the gut microbiota through antibiotics, HFD-FMT, or by administering LPS influenced TNBC chemotherapy responsiveness, lung metastasis, and intestinal inflammation.}, }
@article {pmid36230563, year = {2022}, author = {Tojjari, A and Abushukair, H and Saeed, A}, title = {The Crosstalk between Microbiome and Immunotherapeutics: Myth or Reality.}, journal = {Cancers}, volume = {14}, number = {19}, pages = {}, pmid = {36230563}, issn = {2072-6694}, abstract = {The gut microbiome refers to microorganisms and their genetic material influencing local and systemic inflammation. Inflammation is known to contribute to cancer development, progression, and treatment. Evidence suggests that modulating the gut microbiome may affect responses to various cancer therapies. The gut microbiota has been suggested to have an impact on immunotherapy efficacy, especially the currently widely used immune checkpoint inhibitors in various malignancies. Microbial interventions like fecal microbiota transplantation, various probiotics, or even antibiotics can increase or decrease the tumor's sensitivity to immunotherapy. However, not all tumors react in the same manner, highlighting the tumor microenvironment heterogeneity across tumor types and the influence this has on the crosstalk between the microbiome and therapy outcomes. In this study, we intend to review the association between the gut microbiota and immunotherapy response in cancer patients and the factors regulating this interaction.}, }
@article {pmid36230076, year = {2022}, author = {Li, HY and Huang, SY and Xiong, RG and Wu, SX and Zhou, DD and Saimaiti, A and Luo, M and Zhu, HL and Li, HB}, title = {Anti-Obesity Effect of Theabrownin from Dark Tea in C57BL/6J Mice Fed a High-Fat Diet by Metabolic Profiles through Gut Microbiota Using Untargeted Metabolomics.}, journal = {Foods (Basel, Switzerland)}, volume = {11}, number = {19}, pages = {}, pmid = {36230076}, issn = {2304-8158}, support = {No. 2018YFC1604405//National Key R&amp;D Program of China/ ; No. 2014B020205002//Key Project of Guangdong Provincial Science and Technology Program/ ; }, abstract = {The epidemic of obesity is a serious public health problem. In this study, the effect of theabrownin from dark tea on obesity was evaluated by biochemical tests and nuclear magnetic resonance in C57BL/6J mice fed a high-fat diet. A mixture of antibiotics was used to deplete gut microbiota and then fecal microbiota transplant was used to restore gut microbiota. Untargeted metabolomics was used to reveal the effects of theabrownin on metabolic profiles through gut microbiota. The results showed that theabrownin significantly reduced body weight gain (83.0%) and body fat accumulation (30.29%) without affecting appetite. Also, theabrownin promoted lipid clearance with a hepatoprotective effect. The extra antibiotics disrupted the regulation of theabrownin on weight control while fecal microbiota transplant restored the beneficial regulation. That is, gut microbiota was important for theabrownin to reduce body weight gain. The untargeted metabolomics indicated that 18 metabolites were related to the anti-obesity effect of theabrownin mediated by gut microbiota. Furthermore, phenylalanine metabolism, histidine metabolism, as well as protein digestion and absorption pathway played a role in the anti-obesity of theabrownin. Our findings suggested that theabrownin significantly alleviated obesity via gut microbiota-related metabolic pathways, and theabrownin could be used for the prevention and treatment of obesity.}, }
@article {pmid36227005, year = {2023}, author = {Dogra, S and Oneto, C and Sherman, A and Varughese, R and Yuen, A and Sherman, I and Cohen, A and Luo, Y and Chen, LA}, title = {Long-Term Efficacy and Safety of Fecal Microbiota Transplantation for C. difficile Infections Across Academic and Private Clinical Settings.}, journal = {Journal of clinical gastroenterology}, volume = {57}, number = {10}, pages = {1024-1030}, pmid = {36227005}, issn = {1539-2031}, support = {K23 DK119544/DK/NIDDK NIH HHS/United States ; }, abstract = {PURPOSE: Fecal microbiota transplant (FMT) is increasingly performed for Clostridioides difficile infection (CDI), although long-term efficacy and safety data are limited and are focused on results from academic medical centers rather than private settings where most patients receive care.<br><br>METHODS: Medical records of 165 patients who received FMTs for CDI were reviewed from an academic medical center and an adjacent, unaffiliated private practice. Of these patients, 68 also completed a survey regarding their long-term disease course and interval health.<br><br>RESULTS: CDI resolution occurred in 81.3% (100/123) at the academic center and 95.2% (40/42) in the private setting. Private practice patients were more likely to present with recurrent, rather than refractory, CDI (92.9% vs. 66.7% P <0.001). Those from the academic center were more likely to have comorbid IBD, recent hospitalization, recent proton pump inhibitor use, ongoing immunosuppression, and inpatient FMT (all P values <0.05).Among surveyed patients, 29.4% developed interval comorbidities or changes to pre-existing conditions after a median follow-up of 33.7 months (IQR 13.2 to 44.3&#xa0;mo). Of 30 patients requiring subsequent antibiotics, 13.3% suffered CDI relapse. All subjects who had initially responded to FMT but had a subsequent CDI (17.9%, 10/56) responded to another FMT.<br><br>CONCLUSIONS: In a real-world setting, patients who underwent FMT at academic centers differed significantly in clinical characteristics from those treated at a private practice. In both settings, FMT is an effective treatment for CDI not responding to standard therapies, even after subsequent antibiotic use. New diagnoses following FMT, however, are common and merit further exploration.}, }
@article {pmid36226734, year = {2022}, author = {Sangiuolo, K and Cheng, E and Terala, A and Dubrosa, F and Milanaik, RL}, title = {The gut microbiome: an overview of current trends and risks for paediatric populations.}, journal = {Current opinion in pediatrics}, volume = {34}, number = {6}, pages = {634-642}, doi = {10.1097/MOP.0000000000001186}, pmid = {36226734}, issn = {1531-698X}, mesh = {Adolescent ; Humans ; Child ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Microbiota ; Diet ; *Malnutrition ; }, abstract = {PURPOSE OF REVIEW: Gut health is an increasingly popular topic of discussion among scientists and the general population alike. As interest surrounding the gut microbiome grows, the accessibility to misinformation and unfounded gut health trends to youth is likely to emerge as a public health concern. The purpose of this review is to provide paediatricians with current information about the gut microbiome, as well as explanations and possible risks of the multitude of gut health trends that adolescents may be exposed to.<br><br>RECENT FINDINGS: The gut microbiome is implicated in overall health by playing roles in digestion, immunity and mental health. Novel microbiome-related therapies, such as faecal microbiota transplants, and the gut-brain link show the therapeutic potential of the gut microbiome. However, unproven dietary fads and trends on social media are rampant as well, such as ginger juice shots. In addition, paediatric supplements meant to target gut health are unregulated, yet are highly marketed. Improperly applying these trends and diets may result in risks of malnutrition and body image issues for impressionable children.<br><br>SUMMARY: Increased familiarity regarding the types of gut health trends and diets among young people will allow paediatricians to more effectively advise their patients about potential risks and good gut health practices. Paediatricians and caregivers serve as role models and educators with regard to children's perceptions and management of their gut and overall health.}, }
@article {pmid36222487, year = {2023}, author = {Cuomo, M and Carobbio, A and Aloi, M and Alvisi, P and Banzato, C and Bosa, L and Bramuzzo, M and Campanozzi, A and Catassi, G and D'Antiga, L and Di Paola, M and Felici, E and Fioretti, MT and Gatti, S and Graziano, F and Lega, S and Lionetti, P and Marseglia, A and Martinelli, M and Musto, F and Sansotta, N and Scarallo, L and Zuin, G and Norsa, L}, title = {Induction of Remission With Exclusive Enteral Nutrition in Children With Crohn's Disease: Determinants of Higher Adherence and Response.}, journal = {Inflammatory bowel diseases}, volume = {29}, number = {9}, pages = {1380-1389}, doi = {10.1093/ibd/izac215}, pmid = {36222487}, issn = {1536-4844}, mesh = {Humans ; Child ; Adolescent ; *Crohn Disease/therapy/diagnosis ; Enteral Nutrition ; Retrospective Studies ; Remission Induction ; }, abstract = {BACKGROUND: Exclusive enteral nutrition (EEN) is the first choice to induce remission and promote mucosal healing in pediatric Crohn's disease (CD). However, full adherence to EEN treatment may be problematic for children with CD.<br><br>METHODS: The goal of the current multicenter retrospective study was to define predictive factors of nonadherence to treatment and nonremission at the end of induction treatment. Those data together were analyzed with the ultimate goal of trying to define an individualized induction treatment for children with CD.<br><br>RESULTS: Three hundred seventy-six children with CD from 14 IBD pediatric referral centers were enrolled in the study. The rate of EEN adherence was 89%. Colonic involvement and fecal calprotectin&#x2005;>600 &#x3bc;g/g at diagnosis were found to be associated with a reduced EEN adherence. Exclusive enteral nutrition administered for 8 weeks was effective for inducing clinical remission in 67% of the total cohort. Factors determining lower remission rates were age&#x2005;>15 years and Pediatric Crohn's Disease Activity Index >50.<br><br>CONCLUSION: Although EEN is extremely effective in promoting disease remission, several patients' related factors may adversely impact EEN adherence and response. Personalized treatments should be proposed that weigh benefits and risks based on the patient's disease location, phenotype, and disease activity and aim to promote a rapid control of inflammation to reduce long-term bowel damage.}, }
@article {pmid36216056, year = {2023}, author = {Yi, W and Ji, Y and Gao, H and Luo, S and Pan, R and Song, J and He, Y and Li, Y and Wu, Y and Yan, S and Liang, Y and Sun, X and Jin, X and Mei, L and Cheng, J and Su, H}, title = {Effects of urban particulate matter on gut microbiome and partial schizophrenia-like symptoms in mice: Evidence from shotgun metagenomic and metabolomic profiling.}, journal = {The Science of the total environment}, volume = {857}, number = {Pt 1}, pages = {159305}, doi = {10.1016/j.scitotenv.2022.159305}, pmid = {36216056}, issn = {1879-1026}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Particulate Matter/toxicity ; *Schizophrenia ; Dizocilpine Maleate/pharmacology ; Phosphorylcholine/pharmacology ; Feces ; Estriol ; Estrogens ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Epidemiological evidence reported that particulate matter (PM) was associated with increased schizophrenia (SCZ) risk. Disturbance of gut microbiome was involved in SCZ. However, it remains unclear whether PM induces SCZ-like symptoms and how gut microbiome regulates them. Therefore, a multi-omics animal experiment was conducted to verify how urban PM induces SCZ-like behavior and altered gut microbiota and metabolic pathways.<br><br>METHODS: Using a completely random design, mice were divided into three groups: PM group, control group and MK801 group, which received daily tracheal instillation of PM solution, sterile PBS solution and intraperitoneal injection of MK801 (establish SCZ model), respectively. After a 14-day intervention, feces were collected for multi-omics testing (shotgun metagenomic sequencing and untargeted metabolomic profiling), followed by open field test, tail suspension test, and passive avoidance test. Besides, fecal microbiome of PM group and control group were transplanted into "pseudo-sterile" mice, then behavioral tests were conducted.<br><br>RESULTS: Similar to MK801 group, mice in PM group showed SCZ-like symptoms, including increased spontaneous activity, excitability, anxiety and decreased learning and spatial memory. PM exposure significantly increased the relative abundance of Verrucomicrobia and decreased that of Fibrobacteres et al. The metabolism pathways of estrogen signaling (estriol, 16-glucuronide-estriol and 21-desoxycortisol) and choline metabolism (phosphocholine) were significantly altered by PM exposure. Verrucomicrobia was negatively correlated with the level of estriol, which was correlated with decreased learning and spatial memory. Fibrobacteres and Deinococcus-Thermus were positively correlated with the level of phosphocholine, which was correlated with increased spontaneous activity, excitability and anxiety. Fecal microbiome transplantation from PM group mice reproduced excitability and anxiety symptoms.<br><br>CONCLUSIONS: Exposure to PM may affect composition of gut microbiome and alterations of estrogen signaling pathway and choline metabolism pathway, which were associated with partial SCZ-like behaviors. But whether gut microbiome regulates these metabolic pathways and behaviors remains to be determined.}, }
@article {pmid36214691, year = {2022}, author = {Yan, X and Feng, Y and Hao, Y and Zhong, R and Jiang, Y and Tang, X and Lu, D and Fang, H and Agarwal, M and Chen, L and Zhao, Y and Zhang, H}, title = {Gut-Testis Axis: Microbiota Prime Metabolome To Increase Sperm Quality in Young Type 2 Diabetes.}, journal = {Microbiology spectrum}, volume = {10}, number = {5}, pages = {e0142322}, pmid = {36214691}, issn = {2165-0497}, mesh = {Male ; Mice ; Animals ; Testis ; *Diabetes Mellitus, Type 2/therapy ; Semen Analysis ; Butyric Acid ; Blood Glucose ; Eicosapentaenoic Acid ; Docosahexaenoic Acids ; Antioxidants ; Semen ; *Gastrointestinal Microbiome ; Spermatozoa ; Metabolome ; Testosterone ; Alginates ; }, abstract = {Young type 2 diabetes (T2D) affects 15% of the population, with a noted increase in cases, and T2D-related male infertility has become a serious issue in recent years. The current study aimed to explore the improvements of alginate oligosaccharide (AOS)-modified gut microbiota on semen quality in T2D. The T2D was established in young mice of 5 weeks of age with a blood glucose level of 21.2 ± 2.2 mmol/L, while blood glucose was 8.7 ± 1.1 mM in control animals. We discovered that fecal microbiota transplantation (FMT) of AOS-improved microbiota (A10-FMT) significantly decreased blood glucose, while FMT of gut microbiota from control animals (Con-FMT) did not. Sperm concentration and motility were decreased in T2D to 10% to 20% of those in the control group, while A10-FMT brought about a recovery of around 5- to 10-fold. A10-FMT significantly increased small intestinal Allobaculum, while it elevated small intestinal and cecal Lactobacillus in some extent, blood butyric acid and derivatives and eicosapentaenoic acid (EPA), and testicular docosahexaenoic acid (DHA), EPA, and testosterone and its derivatives. Furthermore, A10-FMT improved liver functions and systemic antioxidant environments. Most importantly, A10-FMT promoted spermatogenesis through the improvement in the expression of proteins important for spermatogenesis to increase sperm concentration and motility. The underlying mechanisms may be that A10-FMT increased gut-beneficial microbes Lactobacillus and Allobaculum to elevate blood and/or testicular butyric acid, DHA, EPA, and testosterone to promote spermatogenesis and thus to ameliorate sperm concentration and motility. AOS-improved gut microbes could emerge as attractive candidates to treat T2D-diminished semen quality. IMPORTANCE A10-FMT benefits gut microbiota, liver function, and systemic environment via improvement in blood metabolome, consequently to favor the testicular microenvironment to improve spermatogenesis process and to boost T2D-diminished semen quality. We established that AOS-improved gut microbiota may be used to boost T2D-decreased semen quality and metabolic disease-related male subfertility.}, }
@article {pmid36213281, year = {2022}, author = {Wu, L and Li, MQ and Xie, YT and Zhang, Q and Lu, XJ and Liu, T and Lin, WY and Xu, JT and Wu, QP and He, XX}, title = {Washed microbiota transplantation improves patients with high blood glucose in South China.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {985636}, pmid = {36213281}, issn = {1664-2392}, mesh = {Animals ; Blood Glucose/metabolism ; Cholesterol ; *Gastrointestinal Microbiome ; Glycated Hemoglobin ; *Hyperglycemia/prevention &amp; control ; Hypoglycemic Agents ; Lipids ; Retrospective Studies ; Triglycerides ; }, abstract = {BACKGROUND AND AIMS: Although fecal microbiota transplantation (FMT) from healthy donors has been shown to have hypoglycemic effects in animal models of diabetes, its clinical impact in patients with abnormal blood glucose metabolism is unclear, especially in southern Chinese populations. The aim of this study was to investigate the feasibility and efficacy of washed microbiota transplantation (WMT) in the treatment of abnormal blood glucose metabolism in a population in southern China.<br><br>METHODS: The clinical data of patients with different indications who received 1-3 treatments of WMT were retrospectively collected. The changes of blood glucose, blood lipids, blood pressure, liver function and blood routine before and after WMT were compared, such as fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), systolic blood pressure (SBP), white blood cells (WBC), lymphocytes (LY) and platelets (PLT), etc.<br><br>RESULTS: A total of 195 patients were included in the First Affiliated Hospital of Guangdong Pharmaceutical University, including 20 patients with high blood glucose and 175 patients with normal blood glucose. WMT has a significant effect in reducing short term blood glucose level (FBG) in patients with high blood glucose (p < 0.05). The fasting blood glucose (FBG) of 72.22% of patients with high blood glucose decreased to normal in a short term (about 1 month) (p < 0.001); In the medium term (about 2 months), there was a significant hypolipidemic (TG) (p = 0.043) effect, long term (about 6 months) significant blood pressure lowering (SBP, p = 0.048) effect. Overall, WMT significantly reduced the risk of high risk classes of Atherosclerotic Cardiovascular Disease (ASCVD) in the short term (p = 0.029) and medium term (p = 0.050).<br><br>CONCLUSION: WMT can significantly improve blood glucose in patients with high blood glucose, and there is no long-term elevated risk of blood glucose and ASCVD. FBG levels were significantly reduced in both the short and medium term in patients with high blood glucose treated with WMT. Therefore, the regulation of gut microbiota by WMT may provide a new clinical approach for the treatment of abnormal blood glucose metabolism.}, }
@article {pmid36212891, year = {2022}, author = {Luo, D and Yang, L and Pang, H and Zhao, Y and Li, K and Rong, X and Guo, J}, title = {Tianhuang formula reduces the oxidative stress response of NAFLD by regulating the gut microbiome in mice.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {984019}, pmid = {36212891}, issn = {1664-302X}, abstract = {BACKGROUND: The gut microbiome affects the occurrence and development of NAFLD, but its mechanism has not yet been fully elucidated. Chinese medicine is a new treatment strategy to improve NAFLD by regulating the gut microbiome. Tianhuang formula (TH) has been proved to have a lipid-lowering effect in which constituents of ginsenoside Rb1, ginsenoside Rg1, ginsenoside Rb, ginsenoside Re, and ginsenoside R1 from Panax notoginseng and berberine, palmatine, and coptisine from Coptis chinensis have low drug permeability, which results in poor intestinal absorption into the human body, and are thus able to come into contact with the gut microflora for a longer time. Therefore, it might be able to influence the gut microbial ecosystem, but it still needs to be investigated.<br><br>METHOD: The characteristics of the gut microbiome were represented by 16S rRNA sequencing, and the metabolites in intestinal contents and liver were discovered by non-targeted metabolomics. Correlation analysis and fermentation experiments revealed the relationship between the gut microbiome and metabolites. Blood biochemical indicators, liver function indicators, and oxidation-related indicators were assayed. H&amp;E staining and Oil Red O staining were used to analyze the characteristics of hepatic steatosis. RT-qPCR and western blotting were used to detect the expression of genes and proteins in liver tissues, and fecal microbial transplantation (FMT) was performed to verify the role of the gut microbiome.<br><br>RESULTS: Gut microbiome especially Lactobacillus reduced, metabolites such as 5-Methoxyindoleacetate (5-MIAA) significantly reduced in the liver and intestinal contents, the level of hepatic GSH and SOD reduced, MDA increased, and the protein expression of Nrf2 also reduced in NAFLD mice induced by high-fat diet (HFD). The normal diet mice transplanted with NAFLD mice feces showed oxidative liver injury, indicating that the NAFLD was closely related to the gut microbiome. TH and TH-treated mice feces both can reshape the gut microbiome, increase the abundance of Lactobacillus and the content of 5-MIAA in intestinal contents and liver, and improve oxidative liver injury. This indicated that the effect of TH improving NAFLD was related to the gut microbiome, especially Lactobacillus. 5-MIAA, produced by Lactobacillus, was proved with fermentation experiments in vitro. Further experiments proved that 5-MIAA activated the Nrf2 pathway to improve oxidative stress in NAFLD mice induced by HFD. TH reshaped the gut microbiome, increased the abundance of Lactobacillus and its metabolite 5-MIAA to alleviate oxidative stress, and improved NAFLD.<br><br>CONCLUSION: The study has demonstrated a mechanism by which the gut microbiome modulated oxidative stress in NAFLD mice induced by HFD. The traditional Chinese medicine TH improved NAFLD by regulating the gut microbiome, and its mechanism was related to the "Lactobacillus-5-MIAA-Nrf2" pathway. It provided a promising way for the intervention of NAFLD.}, }
@article {pmid36212876, year = {2022}, author = {Li, Y and Li, X and Wu, Y and Zhang, W}, title = {Effects of fecal microbiota transplantation from yaks on weaning diarrhea, fecal microbiota composition, microbial network structure and functional pathways in Chinese Holstein calves.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {898505}, pmid = {36212876}, issn = {1664-302X}, abstract = {This study was conducted to investigate the effect of fecal microbiota transplantation (FMT) from yaks on weaning diarrhea, fecal microbiota composition, microbial network structure and functional pathways in Chinese Holstein Calves. In this study, 50 calves were randomly divided into five groups of 10 each: NC group (no supplementation), Control group (normal saline), low concentration FMT group (LFMT, 1 × 10[8] CFU/ml), high concentration FMT group (HMFT, 1 × 10[9] CFU/ml), and sterilized FMT group (SMFT, sterilized bacterial solution). The test lasted for 30 days. We found that FMT reduced the incidence of diarrhea in weaned calves, and the anti-diarrhea effect of LFMT was stronger than those of HFMT and SFMT. Calf feces were collected by rectal palpation on days 5, 10, 15, and 20 post-weaning, and high-throughput sequencing of bacterial 16S rRNA and fungal internal transcribed spacer region of fecal microbiota was performed. We observed that the richness and diversity of bacterial microbiota in the LFMT, HFMT, and SFMT groups were higher than those in the NC and Control groups at day 20 after weaning. The treatment had a significant effect on bacterial richness (p < 0.05), but not on fungal diversity or richness. The analysis of gut microbiome showed that Firmicutes and Bacteroides were the main bacterial phyla in the feces of weaned calves, and norank_ f Muribaculaceae, UCG-005, Rikenellaceae_RC9_gut_group, Bacteroides, and Blautia were the main genera. Ascomycota and Basidiomycota were the main fungal phyla. Compared to abundance parameters in the Control and NC groups, relative abundances of Firmicutes in the FMT groups increased at different time points after weaning. The relative abundance of Blautia and Lactobacillus in the LFMT group increased significantly after weaning. In addition, abundances of Ruminococcus and Romboutsia, which produce short-chain fatty acids, were also increased in different FMT groups. FMT significantly increased the relative abundance of beneficial bacteria, enhanced the complexity of the fecal microbial network, and promoted important metabolic and cellular processes in weaned calves. In conclusion, our study provides a reference and theoretical basis for FMT to prevent calf weaning diarrhea and other intestinal diseases in ruminants.}, }
@article {pmid36212607, year = {2022}, author = {Nigam, M and Panwar, AS and Singh, RK}, title = {Orchestrating the fecal microbiota transplantation: Current technological advancements and potential biomedical application.}, journal = {Frontiers in medical technology}, volume = {4}, number = {}, pages = {961569}, pmid = {36212607}, issn = {2673-3129}, abstract = {Fecal microbiota transplantation (FMT) has been proved to be an effective treatment for gastrointestinal disorders caused due to microbial disbalance. Nowadays, this approach is being used to treat extragastrointestinal conditions like metabolic and neurological disorders, which are considered to have their provenance in microbial dysbiosis in the intestine. Even though case studies and clinical trials have demonstrated the potential of FMT in treating a variety of ailments, safety and ethical concerns must be answered before the technique is widely used to the community's overall benefit. From this perspective, it is not unexpected that techniques for altering gut microbiota may represent a form of medication whose potential has not yet been thoroughly addressed. This review intends to gather data on recent developments in FMT and its safety, constraints, and ethical considerations.}, }
@article {pmid36208299, year = {2022}, author = {Wang, YZ and Xiao, FF and Xiao, YM and Li, XL and Hu, H and Hong, K and Li, D and Le, J and Yu, GJ and Zhang, T}, title = {Fecal microbiota transplantation relieves abdominal bloating in children with functional gastrointestinal disorders via modulating the gut microbiome and metabolome.}, journal = {Journal of digestive diseases}, volume = {23}, number = {8-9}, pages = {482-492}, doi = {10.1111/1751-2980.13135}, pmid = {36208299}, issn = {1751-2980}, support = {81870373//National Natural Science Foundation of China/ ; 81900472//National Natural Science Foundation of China/ ; 22ZR1451800//Natural Science Foundation of Shanghai/ ; }, mesh = {Male ; Humans ; Child ; Female ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; *Gastrointestinal Diseases/therapy ; Metabolome ; Bacteria ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in functional gastrointestinal disorders (FGIDs) in children with abdominal bloating and changes in their gut microbiome and metabolome.<br><br>METHODS: Twelve pediatric FGID patients with predominant abdominal bloating who underwent FMT were enrolled in the study. Fourteen healthy controls and four stool donors were included for analysis. Clinical responses were assessed at 8&#x2009;weeks after FMT. Fecal bacterial composition was determined by 16S rRNA gene sequencing. The fecal metabolome was measured by targeted metabolomics analysis.<br><br>RESULTS: Median age of the 12 children with FGIDs was 6&#x2009;years, and nine were boys. Abdominal bloating was relieved in all patients by FMT at 8&#x2009;weeks. Meanwhile, FMT significantly improved abdominal pain and diarrhea. The a diversity was significantly lower in the FGID patients, while the fecal microbial community (&#x3b2; diversity) separated from that of healthy control (HCs). The relative abundances of multiple bacterial genera were significantly changed in the feces of the pediatric FGID patients. The levels of several short-chain fatty acids were lower, and lactic acid level was higher in FGID patients than in HCs. Altered bacterial composition was correlated with changes in the fecal metabolite profile and clinical symptoms in FGID patients. FMT modulated fecal microbiome and metabolome in FGID children toward a healthy state.<br><br>CONCLUSIONS: FMT relieves abdominal bloating and modulates fecal microbiome and metabolome toward a healthy state in children with FGIDs. FMT may provide an alternative therapy for children with FGIDs and abdominal bloating.}, }
@article {pmid36206121, year = {2022}, author = {Perez, R and Khanna, S and Tillotson, GS and Lett, JE and Prince, MA and Lattimer, C}, title = {Reducing Recurrence and Complications Related to Clostridioides difficile Infection: A Panel Discussion Summary.}, journal = {Professional case management}, volume = {27}, number = {6}, pages = {277-287}, pmid = {36206121}, issn = {1932-8095}, mesh = {Aftercare ; Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/drug therapy/prevention &amp; control ; Humans ; Patient Discharge ; Proton Pump Inhibitors/therapeutic use ; Quality of Life ; }, abstract = {BACKGROUND: The Centers for Disease Control and Prevention identifies Clostridioides difficile infection (CDI) as an urgent threat to people and health care systems. CDI leads to high health care utilizations and results in significantly reduced quality of life for patients. The high burden of disease is seen across all health care settings, outside of the hospital, in the community, and in younger people. Individuals with CDI transition from hospitals to long-term care facilities to the community, and management of these transitions can reduce the incidence of recurrence and rehospitalization.<br><br>PURPOSE: The most common cause of diarrhea occurring in a health care setting is Clostridioides difficile and is also the cause of antibiotic-associated colitis (L. C. McDonald, 2021). The infection results from a disruption in the microbial flora of the gastrointestinal tract, mostly after antibiotic use or other medications such as proton pump inhibitors (PPIs). As a result, infected individuals are colonized and shed the spores into the environment, exposing others-goals of treatment focus on reducing the exposure and individual susceptibility. Although the incidence of C. diff is stable, recurrence is increasing significantly, with severe complications also a concern. The increased incidence and potential for life-threatening conditions require reducing initial exposure, supporting prescribed treatment, and preventing recurrence.<br><br>PRIMARY PRACTICE SETTINGS: C. diff infection can be contracted in health care facilities and in the community. Case managers from nearly all practice settings may encounter patients with the infection.<br><br>FINDINGS/CONCLUSIONS: To avert the devastating complications of Clostridioides difficile infection, case managers play an essential role in the prevention of recurrence with education, advocacy of best practices, effective care coordination, and thorough transitions of care. Each recurrence of C. diff infection leaves the patient vulnerable to the potential for surgical intervention, sepsis, and death.<br><br>Mitigating the risk for readmission and recurrence will enhance C. diff infection care, safety, and outcomes to improve a patient's health care journey and quality of life. Case managers need to take a primary role in the transition and care coordination processes, including patient and support system education, coordination of any postdischarge services, connection to providers, adherence support activities, and follow-up for improvement or changes in condition. Supportive adherence activities and prevention education can result in the avoidance of recurrence. Case managers are well-equipped to locate resources to assist those patients challenged with the cost of medications, inability to attend appointments, or access basic needs. Although not directly related to C. diff, these challenges contribute to recurrence and readmission. Mitigating risk for readmission and recurrence results in an improved quality of life.}, }
@article {pmid36204709, year = {2022}, author = {Pan, H and Zhou, M and Ju, Z and Luo, J and Jin, J and Shen, L and Zhou, P and Huang, R}, title = {Potential role of gut microbiota-LCA-INSR axis in high fat-diet-induced non-alcoholic fatty liver dysfunction: From perspective of radiation variation.}, journal = {Current research in food science}, volume = {5}, number = {}, pages = {1685-1700}, pmid = {36204709}, issn = {2665-9271}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a progressive disease of the liver covering a range of conditions from hepatic steatosis to liver fibrosis. NAFLD could be induced by High-fat-diet(HFD). Ionizing radiation is widely used in medical diagnosis and therapy as well as is a common risk factor in occupational environment. Whether the exposure of various dose of radiation has effects on HFD-induced NAFLD remains unclear. Here, we reported that radiation exposure promoted HFD-induced NAFLD in a dose-response manner. Furthermore, the gut microbiota composition had significant difference among mice with or without radiation treatment. Specifically, the Bacteroidetes/Firmicutes ratio, the abundance of A. muciniphila, Butyricococcus, and Clostridiaceae decreased significantly in the mice with co-exposure of high dose of radiation and HFD treatment. A fecal transplantation trial (FMT) further verified the role of gut microbiota in the regulation of the liver response to co-exposure of high dose of radiation and HFD treatment. Notably, the gut microbiome analysis showed plasma lithocholic acid (LCA) level increased in the mice with co-exposure of high dose of radiation and HFD treatment. Following antibiotic and probiotic treatments there was a significantly decreased LCA bile acid concentration and subsequent promotion of INSR/PI3K/Akt insulin signaling in the liver tissues. Our results demonstrate that the co-exposure of radiation and HFD aggravates the HFD-induced NAFLD through gut microbiota-LCA-INSR axis. Probiotics supplementation is a potential way to protect against co-exposure of radiation and HFD-induced liver damage. Meanwhile, our study provide a new insight that population with potential HFD-induced damage should pay more attention on preventing from liver damage while exposing radiation.}, }
@article {pmid36203814, year = {2022}, author = {Biazzo, M and Allegra, M and Deidda, G}, title = {Clostridioides difficile and neurological disorders: New perspectives.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {946601}, pmid = {36203814}, issn = {1662-4548}, abstract = {Despite brain physiological functions or pathological dysfunctions relying on the activity of neuronal/non-neuronal populations, over the last decades a plethora of evidence unraveled the essential contribution of the microbial populations living and residing within the gut, called gut microbiota. The gut microbiota plays a role in brain (dys)functions, and it will become a promising valuable therapeutic target for several brain pathologies. In the present mini-review, after a brief overview of the role of gut microbiota in normal brain physiology and pathology, we focus on the role of the bacterium Clostridioides difficile, a pathogen responsible for recurrent and refractory infections, in people with neurological diseases, summarizing recent correlative and causative evidence in the scientific literature and highlighting the potential of microbiota-based strategies targeting this pathogen to ameliorate not only gastrointestinal but also the neurological symptoms.}, }
@article {pmid36201671, year = {2023}, author = {Gainey, AB and Daniels, R and Burch, AK and Hawn, J and Fackler, J and Biswas, B and Brownstein, MJ}, title = {Recurrent ESBL Escherichia coli Urosepsis in a Pediatric Renal Transplant Patient Treated With Antibiotics and Bacteriophage Therapy.}, journal = {The Pediatric infectious disease journal}, volume = {42}, number = {1}, pages = {43-46}, doi = {10.1097/INF.0000000000003735}, pmid = {36201671}, issn = {1532-0987}, mesh = {Humans ; Child ; Adolescent ; *Phage Therapy ; Escherichia coli ; Anti-Bacterial Agents/therapeutic use ; *Kidney Transplantation/adverse effects ; }, abstract = {INTRODUCTION: Treating recurrent multidrug resistant (MDR) urosepsis in pediatric transplant recipients can be challenging. Particularly when antibiotics fail to prevent future occurrence and the nidus is seemingly undiscoverable. While there is an increasing amount of data on phage therapy, to our knowledge, there are no published cases involving pediatric renal transplant recipients. Therefore, we present a challenging clinical case in which phage therapy was used in a pediatric renal transplant recipient who developed recurrent MDR urosepsis with an unclear source.<br><br>CASE PRESENTATION: Our patient was a 17-year-old female who initially developed urosepsis caused by extended-spectrum &#x3b2;-lactamase (ESBL) Escherichia coli , while being treated with an immunosuppressant regimen because of kidney rejection secondary to poor immunosuppression therapy compliance. She was admitted to our hospital intermittently for 4 months with 4 episodes of urosepsis caused by ESBL E. coli . She received multiple courses of antibiotics (mainly ertapenem) and underwent a fecal material transplant to eradicate her ESBL E. coli colonized gastrointestinal tract. Because of recurrent development of urosepsis after antibiotic treatment, she later underwent treatment with a phage cocktail consisting of 2 isolate-specific phages. After a prolonged antibiotic course and subsequent 3-week intravenous phage treatment, she had no ESBL E. coli in her urinary cultures for 4 years post-treatment.<br><br>DISCUSSION: This case highlights the challenges of treating recurrent ESBL E. coli infections in a pediatric renal transplant patient and provides evidence that phage therapy may prove useful in such cases.}, }
@article {pmid36199683, year = {2022}, author = {Zhang, T and Zhang, B and Tian, W and Wang, F and Zhang, J and Ma, X and Wei, Y and Tang, X}, title = {Research trends in ulcerative colitis: A bibliometric and visualized study from 2011 to 2021.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {951004}, pmid = {36199683}, issn = {1663-9812}, abstract = {Background: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease with repeated relapses and remissions. Despite decades of effort, numerous aspects, including the initiating event and pathogenesis of UC, still remain ambiguous, which requires ongoing investigation. Given the mass of publications on UC, there are multidimensional challenges to evaluating the scientific impact of relevant work and identifying the current foci of the multifaceted disease. Accordingly, herein, we aim to assess the global growth of UC research production, analyze patterns of research areas, and evaluate trends in this area. Methods: The Web of Science Core Collection of Clarivate Analytics was searched for articles related to UC published from 2011 to 2021. Microsoft Office Excel 2019 was used to visualize the number of publications over time. Knowledge maps were generated using CiteSpace and VOSviewer to analyze collaborations among countries, institutions, and authors and to present the journey of UC research as well as to reveal the current foci of UC research. Results: A total of 5,088 publications were evaluated in the present study. China had the most publications (1,099, 22.5%). Univ Calif San Diego was the most productive institution (126, 2.48%). William J Sandborn published the greatest number of articles (100, 1.97%). Toshifumi Hibi was the most influential author in the field with a betweenness centrality of 0.53. Inflammatory bowel diseases was identified as the most prolific journal (379, 7.45%). Gastroenterology was the most co-cited journal (3,730, 4.02%). "Vedolizumab," "tofacitinib," "Faecalibacterium prausnitzii," "fecal microbiota transplantation (FMT)," "toll-like receptor 4," and "nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome" were considered the hot topics. Conclusion: In UC research, manuscripts that had high impacts on the scientific community provided an evidence base. UC therapy has entered the era of personalized and precision therapy. As research on FMT, anti-integrin antibodies, Janus kinase inhibitors, and anti-tumor necrosis factor drugs continues to grow, their use in the clinical setting may also expand.}, }
@article {pmid36196151, year = {2022}, author = {Zhang, YW and Cao, MM and Li, YJ and Lu, PP and Dai, GC and Zhang, M and Wang, H and Rui, YF}, title = {Fecal microbiota transplantation ameliorates bone loss in mice with ovariectomy-induced osteoporosis via modulating gut microbiota and metabolic function.}, journal = {Journal of orthopaedic translation}, volume = {37}, number = {}, pages = {46-60}, pmid = {36196151}, issn = {2214-031X}, abstract = {BACKGROUND: Osteoporosis (OP) is a systemic metabolic bone disease characterized by decreased bone mass and destruction of bone microstructure, which tends to result in enhanced bone fragility and related fractures. The postmenopausal osteoporosis (PMOP) has a relatively high proportion, and numerous studies reveal that estrogen-deficiency is related to the imbalance of gut microbiota (GM), impaired intestinal mucosal barrier function and enhanced inflammatory reactivity. However, the underlying mechanisms remain unclear and the existing interventions are also scarce.<br><br>METHODS: In this study, we established a mouse model induced by ovariectomy (OVX) and conducted fecal microbiota transplantation (FMT) by gavage every day for 8 weeks. Subsequently, the bone mass and microarchitecture of mice were evaluated by the micro computed tomography (Micro-CT). The intestinal permeability, pro-osteoclastogenic cytokines expression, osteogenic and osteoclastic activities were detected by the immunohistological analysis, histological examination, enzyme-linked immunosorbent assay (ELISA) and western blot analysis accordingly. Additionally, the composition and abundance of GM were assessed by 16S rRNA sequencing and the fecal short chain fatty acids (SCFAs) level was measured by metabolomics.<br><br>RESULTS: Our results demonstrated that FMT inhibited the excessive osteoclastogenesis and prevented the OVX-induced bone loss. Specifically, compared with the OVX group, FMT enhanced the expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin) and suppressed the release of pro-osteoclastogenic cytokines (tumor necrosis factor-&#x3b1; (TNF-&#x3b1;) and interleukin-1&#x3b2; (IL-1&#x3b2;)). Furthermore, FMT also optimized the composition and abundance of GM, and increased the fecal SCFAs level (mainly acetic acid and propionic acid).<br><br>CONCLUSIONS: Collectively, based on GM-bone axis, FMT prevented the OVX-induced bone loss by correcting the imbalance of GM, improving the SCFAs level, optimizing the intestinal permeability and suppressing the release of pro-osteoclastogenic cytokines, which may be an alternative option to serve as a promising candidate for the prevention and treatment of PMOP in the future.<br><br>This study indicates the ingenious involvement of GM-bone axis in PMOP and the role of FMT in reshaping the status of GM and ameliorating the bone loss in OVX-induced mice. FMT might serve as a promising candidate for the prevention and treatment of PMOP in the future.}, }
@article {pmid36195899, year = {2022}, author = {Wang, J and Zhong, Y and Zhu, H and Mahgoub, OK and Jian, Z and Gu, L and Xiong, X}, title = {Different gender-derived gut microbiota influence stroke outcomes by mitigating inflammation.}, journal = {Journal of neuroinflammation}, volume = {19}, number = {1}, pages = {245}, pmid = {36195899}, issn = {1742-2094}, support = {82171336//National Natural Science Foundation of China/ ; 81870939//National Natural Science Foundation of China/ ; 82071339//National Natural Science Foundation of China/ ; 81771283//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Cytokines/metabolism ; Female ; *Gastrointestinal Microbiome ; Inflammation/etiology ; *Ischemic Stroke ; Male ; Mice ; RNA, Ribosomal, 16S/genetics ; *Stroke/therapy ; }, abstract = {BACKGROUND AND PURPOSE: Stroke is associated with high disability and mortality rates and increases the incidence of organ-related complications. Research has revealed that the outcomes and prognosis of stroke are regulated by the state of the intestinal microbiota. However, the possibility that the manipulation of the intestinal microbiota can alter sex-related stroke outcomes remain unknown.<br><br>METHODS: To verify the different effects of microbiota from different sexes on stroke outcomes, we performed mouse fecal microbiota transplantation (FMT) and established a model of ischemic stroke. Male and female mice received either male or female microbiota through FMT. Ischemic stroke was triggered by MCAO (middle cerebral artery occlusion), and sham surgery served as a control. Over the next few weeks, the mice underwent neurological evaluation and metabolite and inflammatory level detection, and we collected fecal samples for 16S ribosomal RNA analysis.<br><br>RESULTS: We found that when the female mice were not treated with FMT, the microbiota (especially the Firmicutes-to-Bacteroidetes ratio) and the levels of three main metabolites tended to resemble those of male mice after experimental stroke, indicating that stroke can induce an ecological imbalance in the biological community. Through intragastric administration, the gut microbiota of male and female mice was altered to resemble that of the other sex. In general, in female mice after MCAO, the survival rate was increased, the infarct area was reduced, behavioral test performance was improved, the release of beneficial metabolites was promoted and the level of inflammation was mitigated. In contrast, mice that received male microbiota were much more hampered in terms of protection against brain damage and the recovery of neurological function.<br><br>CONCLUSION: A female-like biological community reduces the level of systemic proinflammatory cytokines after ischemic stroke. Poor stroke outcomes can be positively modulated following supplementation with female gut microbiota.}, }
@article {pmid36195536, year = {2022}, author = {An, J and Wang, L and Song, S and Tian, L and Liu, Q and Mei, M and Li, W and Liu, S}, title = {Electroacupuncture reduces blood glucose by regulating intestinal flora in type 2 diabetic mice.}, journal = {Journal of diabetes}, volume = {14}, number = {10}, pages = {695-710}, pmid = {36195536}, issn = {1753-0407}, support = {81570488//National Natural Science Foundation of China/ ; 8177031019//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Anti-Bacterial Agents ; Blood Glucose ; Cytokines ; *Diabetes Mellitus, Experimental ; *Diabetes Mellitus, Type 2/therapy ; *Electroacupuncture ; *Gastrointestinal Microbiome ; I-kappa B Kinase ; *Insulin Resistance ; Mice ; NF-kappa B ; Proto-Oncogene Proteins c-akt ; Tight Junction Proteins ; }, abstract = {BACKGROUND: The development of diabetes is closely related to the gut microbiota in recent studies, which can be influenced by intestinal motility. A few studies report that electroacupuncture (EA) can lower blood glucose. EA can promote colonic motility and influence gut microbes. In this study, we explored the effect of the EA on blood glucose level in mice with type 2 diabetes (T2D) and its mechanism.<br><br>METHODS: The T2D mice model, fecal microbiota transplantation mice model, and Kit[W/Wv] mice model &#xff08;Point mutation of mouse W locus encoding kit gene&#xff09;were used to investigate the effect of EA on blood glucose as well as the mechanism; The blood glucose and insulin resistance level and the intestinal flora were evaluated. The level of intestinal junction protein, inflammatory cytokines in the serum, interstitial cells of Cajal content, and colonic motility were detected. Lastly, the IKK&#x3b2;/NF-&#x3ba;B-JNK-IRS-1-AKT pathway was explored.<br><br>RESULTS: EA lowered the blood glucose level, altered the gut microbiota, and promoted colonic motility in T2D mice. EA-altered microbiota decreased the blood glucose level and insulin resistance in the antibiotics-treated diabetic mice. EA increased tight junction protein, lowered inflammatory factors, and regulated the IKK&#x3b2;/NF-&#x3ba;B-JNK-IRS-1-AKT pathway in the liver and muscles. EA could not reduce the blood glucose and regulated gut microbiota in the Kit[W/Wv] mice model.<br><br>CONCLUSIONS: EA promoted intestinal motility to regulate the intestinal flora, thereby reducing the level of systemic inflammation, and ultimately lowering the blood glucose by the IKK&#x3b2;/NF-&#x3ba;B-JNK-IRS-1-AKT signal pathway.}, }
@article {pmid36193874, year = {2022}, author = {Yang, Z and Chen, Z and Lin, X and Yao, S and Xian, M and Ning, X and Fu, W and Jiang, M and Li, N and Xiao, X and Feng, M and Lian, Z and Yang, W and Ren, X and Zheng, Z and Zhao, J and Wei, N and Lu, W and Roponen, M and Schaub, B and Wong, GWK and Su, Z and Wang, C and Li, J}, title = {Rural environment reduces allergic inflammation by modulating the gut microbiota.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2125733}, pmid = {36193874}, issn = {1949-0984}, mesh = {Animals ; Bacteria/genetics ; Dust ; Endotoxins ; *Gastrointestinal Microbiome ; *Hypersensitivity/microbiology/prevention &amp; control ; Immunoglobulin E ; Inflammation ; Mice ; Ovalbumin ; }, abstract = {Rural environments and microbiota are linked to a reduction in the prevalence of allergies. However, the mechanism underlying the reduced allergies modulated by rural residency is unclear. Here, we assessed gut bacterial composition and metagenomics in urban and rural children in the EuroPrevall-INCO cohort. Airborne dusts, including mattress and rural henhouse dusts, were profiled for bacterial and fungal composition by amplicon sequencing. Mice were repeatedly exposed to intranasal dust extracts and evaluated for their effects on ovalbumin (OVA)-induced allergic airway inflammation, and gut microbiota restoration was validated by fecal microbiota transplant (FMT) from dust-exposed donor mice. We found that rural children had fewer allergies and unique gut microbiota with fewer Bacteroides and more Prevotella. Indoor dusts in rural environments harbored higher endotoxin level and diversity of bacteria and fungi, whereas indoor urban dusts were enriched with Aspergillus and contained elevated pathogenic bacteria. Intranasal administration of rural dusts before OVA sensitization reduced respiratory eosinophils and blood IgE level in mice and also led to a recovery of gut bacterial diversity and Ruminiclostridium in the mouse model. FMT restored the protective effect by reducing OVA-induced lung eosinophils in recipient mice. Together, these results support a cause-effect relationship between exposure to dust microbiota and allergy susceptibility in children and mice. Specifically, rural environmental exposure modulated the gut microbiota, which was essential in reducing allergy in children from Southern China. Our findings support the notion that the modulation of gut microbiota by exposure to rural indoor dust may improve allergy prevention.}, }
@article {pmid36192796, year = {2022}, author = {Yin, L and Huang, G and Khan, I and Su, L and Xia, W and Law, BYK and Wong, VKW and Wu, Q and Wang, J and Leong, WK and Hsiao, WLW}, title = {Poria cocos polysaccharides exert prebiotic function to attenuate the adverse effects and improve the therapeutic outcome of 5-FU in Apc[Min/+] mice.}, journal = {Chinese medicine}, volume = {17}, number = {1}, pages = {116}, pmid = {36192796}, issn = {1749-8546}, support = {20221369//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: As a first-line chemotherapeutic agent, 5-fluorouracil (5-FU) exhibits many side effects, weakening its efficacy in cancer treatment. In this study, we hypothesize that Poria cocos polysaccharides (PCP), a traditional Chinese herbal medicine with various bioactivities and prebiotic effects, might improve the therapeutic effect of 5-FU by restoring the homeostasis of the gut microenvironment and the commensal gut microflora.<br><br>METHODS: Apc[Min/+] mice were employed to evaluate the anti-cancer effect of 5-FU in conjunction with PCP treatment. Body weight and food consumption were monitored weekly. Polyp count was used to assess the anti-cancer effect of PCP and 5-FU. Expressions of mucosal cytokines and gut epithelial junction molecules were measured using qRT-PCR. 16S rRNA gene sequencing of fecal DNAs was used to evaluate the compositional changes of gut microbiota (GM). Transplantation of Lactobacillus johnsonii and Bifidobacterium animalis were performed to verify the prebiotic effects of PCP in improving the efficacy of 5-FU.<br><br>RESULTS: The results showed that PCP treatment alleviated the weight loss caused by 5-FU treatment and reduced the polyp burden in Apc[Min/+] mice. Additionally, PCP treatment eased the cytotoxic effects of 5-FU by reducing the expressions of pro-inflammatory cytokines, increasing the anti-inflammatory cytokines; and significantly improving the gut barriers by enhancing the tight junction proteins and associated adhesion molecules. Furthermore, 16S rRNA gene sequencing data showed that PCP alone or with 5-FU could stimulate the growth of probiotic bacteria (Bacteroides acidifaciens, Bacteroides intestinihominis, Butyricicoccus pullicaecorum, and the genera Lactobacillus, Bifidobacterium, Eubacterium). At the same time, it inhibited the growth of potential pathogens (e.g., Alistipes finegoldii, Alistipes massiliensis, Alistipes putredinis., Citrobacter spp., Desulfovibrio spp., and Desulfovibrio desulfuricans). Moreover, the results showed that transplantation of L.johnsonii and B.animalis effectively reduced the polyp burden in Apc[Min/+] mice being treated with 5-FU.<br><br>CONCLUSION: Our study showed that PCP could effectively improve the anti-cancer effect of 5-FU by attenuating its side effects, modulating intestinal inflammation, improving the gut epithelial barrier, and modulating the gut microbiota of Apc[Min/+] mice.}, }
@article {pmid36191780, year = {2022}, author = {Lv, WJ and Ma, YM and Huang, JY and He, SQ and Li, SP and Lin, J and Chen, R and Lun, JC and Liu, J and Guo, SN}, title = {Polysaccharides derived from Shenling Baizhu San improve colitis via modulating tryptophan metabolism in mice.}, journal = {International journal of biological macromolecules}, volume = {222}, number = {Pt A}, pages = {1127-1136}, doi = {10.1016/j.ijbiomac.2022.09.246}, pmid = {36191780}, issn = {1879-0003}, mesh = {Mice ; Animals ; Tryptophan/metabolism ; *Colitis/chemically induced/drug therapy/microbiology ; *Drugs, Chinese Herbal/pharmacology ; Colon ; Polysaccharides/adverse effects ; Mice, Inbred C57BL ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; }, abstract = {Shenling Baizhu San has beneficial effects on the metabolism of the gut microbiota, however, the mechanisms underlying microbiota metabolites mediated anti-inflammation signaling are not well understood. Previously, we have demonstrated that supplementation with Shenling Baizhu San alleviated antibiotic-associated diarrhea (AAD). The current study intends to investigate the dynamic modulation of Shenling Baizhu San polysaccharides (SP) on colitis from the gut microbiota metabolites perspective. Administration of SP effectively relieved colitis induced by DSS in mice, including alleviating body weight loss, the downregulation of colon proinflammatory mediators, and the promotion of intestinal injury repair. Whereas, the efficacy was eliminated by antibiotics, which demonstrated that the efficacy of SP was dependent on the gut microbiota. Fecal microbiota transplantation (FMT) showed that the efficacy of SP can be transferred to gut microbiota. Serum metabolomics analysis showed that supplementation with SP significantly promoted tryptophan metabolism, which was consistent with the changed structure of the gut microbiota, including Bacteroides, Bifidobacterium and Ruminococcus regulated by SP. Especially, the tryptophan metabolites-kynurenine (KYN) activated the expression of amplifying aryl-hydrocarbon receptor (AhR) and Cyp1A1 to promote IL-10 expression in colon. These data suggested that SP positively affected colitis in mice by regulating tryptophan metabolic function of their gut microbiota.}, }
@article {pmid36189234, year = {2022}, author = {Cai, Y and Zhang, Y and Wang, W and Geng, J}, title = {Prospect of research hotspots in prevention and treatment of diseases based on intestinal microbiome.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {971457}, pmid = {36189234}, issn = {1664-3224}, mesh = {Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; }, abstract = {With the in-depth study of gut microbiota, the methods of preventing and treating diseases have gradually diversified. But there is still lack of precise therapies methods to better treat the diseases. Therefore, researcher must focus on how to accurately regulate gut microbiota to achieve it. In order to promote the rapid development of this field, we provide several insights in gut microbiome-based precision therapies while prospecting the future directions.}, }
@article {pmid36187601, year = {2022}, author = {Al-Beltagi, M and Saeed, NK}, title = {Epilepsy and the gut: Perpetrator or victim?.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {13}, number = {5}, pages = {143-156}, pmid = {36187601}, issn = {2150-5330}, abstract = {The brain and the gut are linked together with a complex, bi-path link known as the gut-brain axis through the central and enteric nervous systems. So, the brain directly affects and controls the gut through various neurocrine and endocrine processes, and the gut impacts the brain via different mechanisms. Epilepsy is a central nervous system (CNS) disorder with abnormal brain activity, causing repeated seizures due to a transient excessive or synchronous alteration in the brain's electrical activity. Due to the strong relationship between the enteric and the CNS, gastrointestinal dysfunction may increase the risk of epilepsy. Meanwhile, about 2.5% of patients with epilepsy were misdiagnosed as having gastrointestinal disorders, especially in children below the age of one year. Gut dysbiosis also has a significant role in epileptogenesis. Epilepsy, in turn, affects the gastrointestinal tract in different forms, such as abdominal aura, epilepsy with abdominal pain, and the adverse effects of medications on the gut and the gut microbiota. Epilepsy with abdominal pain, a type of temporal lobe epilepsy, is an uncommon cause of abdominal pain. Epilepsy also can present with postictal states with gastrointestinal manifestations such as postictal hypersalivation, hyperphagia, or compulsive water drinking. At the same time, antiseizure medications have many gastrointestinal side effects. On the other hand, some antiseizure medications may improve some gastrointestinal diseases. Many gut manipulations were used successfully to manage epilepsy. Prebiotics, probiotics, synbiotics, postbiotics, a ketogenic diet, fecal microbiota transplantation, and vagus nerve stimulation were used successfully to treat some patients with epilepsy. Other manipulations, such as omental transposition, still need more studies. This narrative review will discuss the different ways the gut and epilepsy affect each other.}, }
@article {pmid36187462, year = {2022}, author = {Yao, S and Yagi, S and Ogawa, E and Hirata, M and Miyachi, Y and Iwamura, S and Uozumi, R and Sugimoto, T and Asahara, T and Uemoto, S and Hatano, E}, title = {Dysbiosis and Depletion of Fecal Organic Acids Correlate With the Severity of Rejection After Rat Liver Transplantation.}, journal = {Transplant international : official journal of the European Society for Organ Transplantation}, volume = {35}, number = {}, pages = {10728}, pmid = {36187462}, issn = {1432-2277}, mesh = {Alanine Transaminase ; Animals ; Anti-Bacterial Agents ; Bilirubin ; *Dysbiosis/microbiology ; Fatty Acids, Volatile/analysis ; Immunosuppressive Agents ; *Liver Transplantation/adverse effects ; Rats ; }, abstract = {The impact of T cell-mediated rejection (TCMR) after liver transplantation (LT) on the alterations in the gut microbiota (GM) and associated intestinal environment represented by fecal organic acids (OAs) require further elucidation. A rat allogeneic LT model was prepared without immunosuppressants or antibiotics, and a syngeneic model was used as a control. Qualitative and quantitative analyses of fecal samples at fixed time points were performed. Correlation analyses were also performed between liver function and GMs and OA levels. In the allogeneic TCMR group, the number of predominant obligate anaerobes decreased as liver function declined. Clostridioides difficile, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus were significantly increased. Regarding fecal OA concentration, short-chain fatty acid (SCFA) concentrations were depleted as liver function declined. In contrast, in the syngeneic group, GM and OAs exhibited only slight, transient, and reversible disturbances. In addition, alanine aminotransferase and total bilirubin were positively correlated with the number of Enterobacteriaceae and Enterococcus, and negatively correlated with the fecal concentration of SCFAs. The allogeneic TCMR model demonstrated distinct dysbiosis and depletion of fecal OAs as TCMR progressed after LT. The degree of graft injury was closely related to the number of specific bacterial strains and the concentrations of fecal SCFAs.}, }
@article {pmid36187337, year = {2022}, author = {Huang, HL and Zhu, JQ and Yang, LS and Wu, Q and Shou, DW and Chen, HT and Ma, J and Li, YQ and Xu, HM and Zhou, YJ}, title = {Fecal Microbiota Transplantation Combined with a Low FODMAP Diet for the Treatment of Irritable Bowel Syndrome with Predominant Diarrhea.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {5121496}, pmid = {36187337}, issn = {1942-0994}, mesh = {DNA, Ribosomal ; Diarrhea/therapy ; Diet ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Diseases ; Humans ; *Irritable Bowel Syndrome/therapy ; Prospective Studies ; Quality of Life ; Retrospective Studies ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been found to be effective in irritable bowel syndrome with predominant diarrhea (IBS-D). We conducted this study to determine the impact of a low FODMAP diet (LFD) on the gut microbiota and the efficacy of FMT in the treatment of IBS-D.<br><br>METHODS: A retrospective analysis of a single-arm open-label prospective study was conducted to investigate the impact of FMT alone (n = 40) and FMT+LFD (n = 40) in refractory IBS-D. The IBS-quality of life (QOL), IBS-severity scoring system (SSS), gastrointestinal symptom rating scale (GSRS), Hamilton anxiety scale (HAMA), and Hamilton depression scale (HAMD) were used to evaluate the efficacy, and partial 16S rDNA amplicon sequencing was used to profile the microbiota.<br><br>RESULTS: The response rates were higher in the FMT+LFD group than in the FMT group (1&#x2009;mo, 3&#x2009;mo, 6&#x2009;mo: 70.0% vs. 55.0%, 67.5% vs. 57.5%, 62.5% vs. 27.5%, respectively). The FMT+LFD group showed significantly better improvement in IBS-QOL at 1, 3, and 6 months; IBS-SSS at 6 months; and GSRS at 1 month compared to FMT alone. Changes in HAMA and HAMD were similar in the two groups. The LFD significantly upregulated the FMT-induced microbial diversity (OTUs: 666 vs. 574, Adonis: P = 0.02) and significantly strengthened the upregulation of Bacteroides, Alistipes, and Ruminococcaceae_UCG-002 and the downregulation of Bifidobacterium.<br><br>CONCLUSION: An LFD enhanced the efficacy of FMT, increased the gut microbial diversity after FMT, and strengthened the inhibitory effect of FMT on conditional pathogens.}, }
@article {pmid36185693, year = {2022}, author = {Kang, Y and Cai, Y and Zhao, Y and Yang, Y}, title = {The gut microbiome and Alopecia areata: Implications for early diagnostic biomarkers and novel therapies.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {979876}, pmid = {36185693}, issn = {2296-861X}, abstract = {Alopecia areata (AA) accounts for the autoimmune disorder mediated by T cells, whose prognostic outcome cannot be predicted and curative treatment is unavailable at present. The AA pathogenic mechanism remains largely unclear, even though follicular attack has been suggested to result from that attack of immune privilege-losing hair follicles driven by immunity. Recently, gut microbiota is suggested to have an important effect on immunoregulation under autoimmune situations like AA. Fecal microbial transplantation (FMT) may be used to treat AA. Nonetheless, related research remains at the initial stage. To promote the rapid progress of relevant research, the present work aimed to shed more lights on gut microbiota's effect on AA, early diagnostic biomarker and FMT therapeutics.}, }
@article {pmid36184305, year = {2023}, author = {Lockwood, MB and Chlipala, GE and Maeinschein-Cline, M and DeVon, HA and Lichvar, AB and Samra, MK and Park, CG and Campara, M and Doorenbos, AZ and Tussing-Humphreys, LM and Spaggiari, M and Bronas, UG and Steel, JL and Green, SS}, title = {Pain Interference in End Stage Kidney Disease is Associated with Changes in Gut Microbiome Features Before and After Kidney Transplantation.}, journal = {Pain management nursing : official journal of the American Society of Pain Management Nurses}, volume = {24}, number = {1}, pages = {68-77}, pmid = {36184305}, issn = {1532-8635}, support = {U01 DK123787/DK/NIDDK NIH HHS/United States ; K23 NR018482/NR/NINR NIH HHS/United States ; K24 AT011995/AT/NCCIH NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; L30 NR020114/NR/NINR NIH HHS/United States ; }, mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Gastrointestinal Microbiome/genetics ; *Kidney Failure, Chronic ; Feces ; Pain ; Inflammation ; }, abstract = {BACKGROUND: Pain, a common debilitating symptom among kidney transplant recipients (KTRs), is among the most common and undertreated symptoms after kidney transplantation.<br><br>AIMS: Characterize associations between gut microbiome features and pain interference before and after kidney transplantation.<br><br>DESIGN: Longitudinal, repeated measures study, collecting fecal specimens and pain interference data pretransplant and 3 months posttransplant.<br><br>SETTING: Participants were recruited at the kidney transplant clinic at the University of Illinois Hospital &amp; Health Sciences System.<br><br>PARTICIPANTS/SUBJECTS: 19 living donor kidney transplant recipients.<br><br>METHODS: We assessed fecal microbial community structure with shotgun metagenomic sequencing; we used pain interference scores derived from the Patient-Reported Outcomes Measurement Information System-57.<br><br>RESULTS: We measured a reduction in the Shannon diversity index in both groups after transplantation but observed no significant differences between groups at either time point. We did observe significant differences in fecal microbial Bray-Curtis similarity index among those reporting pain interference pre- transplant versus no pain interference at 3-months posttransplant (R&#xa0;=&#xa0;.306, p&#xa0;=&#xa0;.022), and between pain interference groups at posttransplant (R&#xa0;=&#xa0;.249, p&#xa0;=&#xa0;.041). Pairwise models showed significant differences between groups posttransplant in relative abundances of several taxa, including a 5-fold reduction.&#xdf;in Akkermansia among those with pain interference and a higher relative abundance of taxa associated with chronic inflammation in those with pain interference posttransplant. Functional gene analysis identified two features that were significantly enriched in those with pain interference, including a peptide transport system gene.<br><br>CONCLUSIONS: Gut microbiota community structure differs between groups with and without pain interference at 3 months after kidney transplantation. Several taxa involved in intestinal barrier integrity and chronic inflammation were associated with posttransplant pain.}, }
@article {pmid36184150, year = {2022}, author = {Na, K and Wei, J and Zhang, L and Fang, Y and Li, X and Lu, S and Guo, X}, title = {Effects of chitosan oligosaccharides (COS) and FMT from COS-dosed mice on intestinal barrier function and cell apoptosis.}, journal = {Carbohydrate polymers}, volume = {297}, number = {}, pages = {120043}, doi = {10.1016/j.carbpol.2022.120043}, pmid = {36184150}, issn = {1879-1344}, mesh = {Animals ; Apoptosis ; *Chitosan/adverse effects ; *Colitis/chemically induced ; *Enterotoxigenic Escherichia coli ; Intestinal Mucosa ; Mice ; Oligosaccharides/pharmacology ; }, abstract = {Chitosan oligosaccharides (COS) show the potential to support the intestinal health, but the mechanism and role of COS-derived intestinal microbiota are unknown. We explored the protective effect of direct administration of COS on intestinal barrier function using an in vivo colitis mouse model and an in vitro enterotoxigenic Escherichia coli (ETEC)-challenged IPEC-J2 cell model. COS directly enhanced the intestinal barrier function. COS intervention also promoted the abundance and diversity of intestinal flora. Importantly, FMT intervention with a COS-derived microbiome decreased the disease index level and alleviated histopathological changes, and improved gut barrier function in the colitis model. Both COS and COS-derived microbiota suppressed ETEC-induced cellular apoptosis in IPEC-J2 cells. This study firstly confirms transplantation of COS-modified fecal microbiota can enhance the intestinal barrier function. The mechanism underlying COS benefits is due to a direct intervention by COS supplementation and an indirect improvement of the gut microbiota induced by COS exposure.}, }
@article {pmid36183340, year = {2022}, author = {Mironova, M and Ehrlich, AC and Grinspan, A and Protano, MA}, title = {Fecal microbiota transplantation may reduce the mortality of patients with severe and fulminant Clostridioides difficile infection compared to standard-of-care antibiotics in a community hospital.}, journal = {Journal of digestive diseases}, volume = {23}, number = {8-9}, pages = {500-505}, doi = {10.1111/1751-2980.13134}, pmid = {36183340}, issn = {1751-2980}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; Hospitals, Community ; Treatment Outcome ; Recurrence ; *Clostridium Infections/drug therapy ; }, abstract = {OBJECTIVES: Clostridioides difficile infection (CDI) is known for significant morbidity and mortality. Fecal microbiota transplantation (FMT) is an effective therapy for recurrent and resistant CDI. However, its impact on the mortality rate of patients with severe and fulminant CDI has not been rigorously studied yet. We aimed to evaluate the effectiveness of FMT on the mortality rate of patients with severe or fulminant CDI in a community hospital system.<br><br>METHODS: Our study included 106 inpatients with severe or fulminant CDI. Both standard-of-care (SOC) and FMT were provided to 14 (13.2%) patients (the FMT group). SOC antibiotics alone were provided to 92 (86.8%) patients, out of whom 28 patients were included via propensity score matching in a 2:1 ratio (the SOC group). The primary outcome was defined as the composite end-point of mortality during admission, within 30 and 90&#x2009;days after discharge, and discharge with comfort measures only. Each component was a secondary end-point.<br><br>RESULTS: The primary outcome rate in the FMT group was 7.1% (1/14) compared to 25.0% (7/28) in the SOC group. Univariate analysis demonstrated that FMT decreases mortality (odds ratio&#xa0;[OR] 0.08, 95% confidence interval [CI] 0.01-0.58, P&#xa0;=&#xa0;0.01). However, multivariate regression did not show statistical significance (OR 0.15, 95% CI 0.01-2.53, P&#xa0;=&#xa0;0.19), possibly due to the small sample size.<br><br>CONCLUSIONS: FMT may decrease the mortality of patients with severe and fulminant CDI. Large studies are needed to validate these findings.}, }
@article {pmid36183156, year = {2023}, author = {Kim, YM and Choi, JO and Cho, YJ and Hong, BK and Shon, HJ and Kim, BJ and Park, JH and Kim, WU and Kim, D}, title = {Mycobacterium potentiates protection from colorectal cancer by gut microbial alterations.}, journal = {Immunology}, volume = {168}, number = {3}, pages = {493-510}, doi = {10.1111/imm.13586}, pmid = {36183156}, issn = {1365-2567}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Tuberculosis ; *Mycobacterium bovis ; *Mycobacterium tuberculosis ; *Colorectal Neoplasms ; BCG Vaccine ; }, abstract = {Not only are many Mycobacteria pathogens, but they can act as strong non-specific immunopotentiators, generating beneficial effects on the pathogenesis of some diseases. However, there has been no direct evidence of the effect of mycobacterial species on colorectal cancer (CRC). Herein, we showed that there may be a meaningful inverse correlation between the incidence of tuberculosis and CRC based on global statistics and that heat-killed Mycobacterial tuberculosis and live Mycobacterium bovis (Bacillus Calmette-Guérin strain) could ameliorate CRC development. In particular, using a faecal microbiota transplantation and a comparison between separate housing and cohousing, we demonstrated that the gut microbiota is involved in the protective effects. The microbial alterations can be elucidated by the modulation of antimicrobial activities including those of the Reg3 family genes. Furthermore, interleukin-22 production by T helper cells contributed to the anti-inflammatory activity of Mycobacteria. Our results revealed a novel role of Mycobacteria involving gut microbial alterations in dampening inflammation-associated CRC and an immunological mechanism underlying the interaction between microbes and host immunity.}, }
@article {pmid36182105, year = {2022}, author = {Landau, HJ and Orlando, E and Rodriguez, ES and Applebaum, A and Mitchell, HR and Peled, JU and Khan, N and Funnell, T and Chung, D and Scordo, M and Shah, GL and LeStrange, NJ and Hambright, KA and McElrath, CM and Cazeau, N and Devlin, SM and Perales, MA and Giralt, SA}, title = {Pilot Trial of Homebound Hematopoietic Cell Transplantation.}, journal = {Transplantation and cellular therapy}, volume = {28}, number = {12}, pages = {832.e1-832.e7}, pmid = {36182105}, issn = {2666-6367}, support = {K08 HL143189/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Quality of Life ; Pilot Projects ; *Hematopoietic Stem Cell Transplantation/methods ; Transplantation, Autologous/methods ; Melphalan/therapeutic use ; *Multiple Myeloma/therapy ; *Immunoglobulin Light-chain Amyloidosis/drug therapy ; }, abstract = {For eligible patients with multiple myeloma (MM) and amyloid light chain (AL) amyloidosis, high-dose chemotherapy and autologous hematopoietic cell transplantation (HCT) is a standard and widely used consolidation therapy. Autologous HCT requires specialized care at a transplantation center and investment from patients and caregivers. We studied the safety and feasibility of delivering transplantation care in a homebound setting to decrease the burden of therapy and increase access to autologous HCT. Patients with MM and AL amyloidosis undergoing autologous HCT were eligible if they resided in designated ZIP codes and had a full-time caregiver, Wi-Fi connection, HCT Comorbidity Index ≤3, and Karnofsky Performance Status score ≥80. High-dose melphalan (on day -2) and hematopoietic cell reinfusion (day 0) were administered in the outpatient clinic. Protocol-specific home care was provided from day +1 through engraftment. Patients were assessed and blood was drawn daily by advanced practice providers. Interventions were delivered by registered nurses. Attending physicians communicated daily through telemedicine. Quality of life, patient and caregiver satisfaction, and fecal microbiota profiling data were collected. Fifteen patients were enrolled and received transplantation care at home starting on day +1 following hematopoietic cell infusion. Patients remained in the program for an average of 12 days and required an average of 2 outpatient visits while receiving home care. Seven of 15 patients were admitted for a median of 4 days (range, 3 to 10 days); admission occurred on day +7 in 5 patients, on day +8 in 1 patient, and on day +12 in 1 patient for neutropenic fever in 2 patients, fever attributed to engraftment syndrome in 2 patients, diarrhea in 2 patients, and dehydration in 1 patient. Only 1 patient had a documented infection (Clostridioides difficile). One patient admitted with neutropenic fever required intensive care unit admission for a gastrointestinal bleed. Forty-seven percent of the patients experienced a grade ≥3 nonhematologic toxicity. There were no deaths on the study. Patients and caregivers reported high satisfaction with care. Microbiota diversity patterns were similar to those of autologous HCT recipients who did not receive post-HCT care at home, although a subset of the cohort maintained microbiota diversity throughout. Homebound HCT in an urban setting is safe and feasible, with less than one-half of patients requiring inpatient admission. Despite increased patient and caregiver responsibility in the homebound setting compared with an inpatient setting, patient and caregiver satisfaction was high. These results support expansion of homebound transplantation care programs.}, }
@article {pmid36182084, year = {2022}, author = {Zhang, T and Cheng, JK and Hu, YM}, title = {Gut microbiota as a promising therapeutic target for age-related sarcopenia.}, journal = {Ageing research reviews}, volume = {81}, number = {}, pages = {101739}, doi = {10.1016/j.arr.2022.101739}, pmid = {36182084}, issn = {1872-9649}, mesh = {Aging/physiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Muscle, Skeletal/physiology ; *Sarcopenia ; }, abstract = {Sarcopenia is characterized by a progressive loss of skeletal muscle mass and function with aging. Recently, sarcopenia has been shown to be closely related with gut microbiota. Strategies such as probiotics and fecal microbiota transplantation have shown potential to ameliorate the muscle loss. This review will focus on the age-related sarcopenia, in particular on the relationship between gut microbiota and age-related sarcopenia, how gut microbiota is engaged in sarcopenia, and the potential role of gut microbiota in the treatment of age-related sarcopenia.}, }
@article {pmid36181412, year = {2023}, author = {Yao, J and Fekadu, G and Ng, SC and You, JHS}, title = {Fecal microbiota transplantation for patients with active ulcerative colitis: A cost-effectiveness analysis.}, journal = {Journal of gastroenterology and hepatology}, volume = {38}, number = {1}, pages = {70-78}, doi = {10.1111/jgh.16015}, pmid = {36181412}, issn = {1440-1746}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy ; Cost-Effectiveness Analysis ; Cost-Benefit Analysis ; Enema ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIM: Growing studies have demonstrated clinical benefits of fecal microbiota transplantation (FMT) therapy (administered by colonoscopy, enema, or both) for active ulcerative colitis (UC). This study aimed to evaluate the cost-effectiveness of standard treatment with and without FMT therapy for mild-to-moderate active UC from the perspective of US healthcare provider.<br><br>METHODS: A 10-year Markov model was developed to evaluate the costs and quality-adjusted life-years (QALYs) of standard treatment plus FMT therapy versus standard treatment alone. Model inputs were retrieved from publish data in literature. Base-case and sensitivity analyses were performed.<br><br>RESULTS: In the base-case analysis, standard treatment plus FMT therapy was more effective than standard treatment alone (by 0.068 QALYs). Comparing to standard treatment alone, standard treatment plus FMT therapy varied from cost-saving to incremental cost, subject to the number of FMT administrations. One-way sensitivity analysis identified the relative risk of achieving remission with FMT therapy to be the most influential factor on the incremental cost-effectiveness ratio of standard treatment plus FMT therapy. Monte-Carlo simulations showed that standard treatment plus FMT therapy with 3 and 6 administrations per FMT course was cost-effective (at willingness-to-pay threshold&#xa0;=&#xa0;50&#xa0;000 USD/QALY) in 90.77% and 67.03% of time, respectively.<br><br>CONCLUSIONS: Standard treatment plus FMT therapy appears to be more effective in gaining higher QALYs than standard therapy alone for patients with mild-to-moderate active UC. Cost-effectiveness of standard treatment plus FMT therapy is highly subject to the relative improvement in achieving remission with standard therapy plus FMT therapy and number of FMT administrations per FMT course.}, }
@article {pmid36181407, year = {2023}, author = {Shen, J and Guo, H and Liu, S and Jin, W and Zhang, ZW and Zhang, Y and Liu, K and Mao, S and Zhou, Z and Xie, L and Wang, G and Hao, H and Liang, Y}, title = {Aberrant branched-chain amino acid accumulation along the microbiota-gut-brain axis: Crucial targets affecting the occurrence and treatment of ischaemic stroke.}, journal = {British journal of pharmacology}, volume = {180}, number = {3}, pages = {347-368}, doi = {10.1111/bph.15965}, pmid = {36181407}, issn = {1476-5381}, support = {BK20211224//Jiangsu Natural Science Funds/ ; 2021YFA1301300//Key Special Projects of National Key Research and Development Plan/ ; SKLNMZZ202001//Project of State Key Laboratory of Natural Medicines/ ; H2021208006//Natural Science Foundation of Hebei Province/ ; C2021418001//Natural Science Foundation of Hebei Province/ ; H2020208025//Natural Science Foundation of Hebei Province/ ; H2020208022//Natural Science Foundation of Hebei Province/ ; H2021302001//Natural Science Foundation of Hebei Province/ ; 82274194//National Natural Science Foundation of China/ ; }, mesh = {Rats ; Animals ; *Stroke/drug therapy/metabolism ; *Brain Ischemia/drug therapy/metabolism ; Brain-Gut Axis ; *Ischemic Stroke/drug therapy ; Amino Acids, Branched-Chain/metabolism ; }, abstract = {BACKGROUND AND PURPOSE: Although increasing evidence illustrated that the bidirectional communication between the brain and the gut is closely related to the occurrence of various complex diseases. Limited effort has been made to explore the influence of intestinal flora on the risk of ischaemic stroke. The present study aims to identify microbiota and specialized microbiota metabolites related to the occurrence and treatment of ischaemic stroke.<br><br>EXPERIMENTAL APPROACH: The role of microbiota in the occurrence and the treatment of ischaemic stroke was evaluated on ischaemia/reperfusion (I/R), pseudo-germ-free and faecal transplantation animals. The target microbiota and specialized metabolites were identified by comparing their distribution in flora and metabolomic profiles in ischaemic stroke patients and animals with compared with healthy controls. The effects and mechanisms involved of the targeted metabolites in ischaemic stroke were explored in ischaemia/reperfusion rats, hypoxia/reoxygenation PC12 cells and LPS-induced inflammatory BV2 cells.<br><br>KEY RESULTS: Both ischaemic stroke patients and I/R rats had significant accumulation of branched-chain amino acids, which were closely associated with gut microflora dysbiosis and the development of ischaemic stroke. Lactobacillus helveticus (L.hel) and Lactobacillus brevis (L.bre) are identified as the microbiota most affected by ischaemia/reperfusion modelling and treatment. L.hel and L.bre colonization exhibited significant neuroprotective activity and could greatly alleviate the accumulation of branched-chain amino acids. In addition, branched-chain amino acid (BCAA) accumulation was shown to exacerbate microglia-induced neuroinflammation by activating AKT/STAT3/NF-&#x3ba;B signalling.<br><br>CONCLUSION AND IMPLICATIONS: Our findings demonstrated the crucial role of intestinal flora and microbiota metabolites in the occurrence and treatment of ischaemic stroke.}, }
@article {pmid36180583, year = {2022}, author = {Hitch, TCA and Hall, LJ and Walsh, SK and Leventhal, GE and Slack, E and de Wouters, T and Walter, J and Clavel, T}, title = {Microbiome-based interventions to modulate gut ecology and the immune system.}, journal = {Mucosal immunology}, volume = {15}, number = {6}, pages = {1095-1113}, pmid = {36180583}, issn = {1935-3456}, support = {BBS/E/F/00044409/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Prebiotics ; *Microbiota ; *Gastrointestinal Microbiome ; *Probiotics ; Immune System ; }, abstract = {The gut microbiome lies at the intersection between the environment and the host, with the ability to modify host responses to disease-relevant exposures and stimuli. This is evident in how enteric microbes interact with the immune system, e.g., supporting immune maturation in early life, affecting drug efficacy via modulation of immune responses, or influencing development of immune cell populations and their mediators. Many factors modulate gut ecosystem dynamics during daily life and we are just beginning to realise the therapeutic and prophylactic potential of microbiome-based interventions. These approaches vary in application, goal, and mechanisms of action. Some modify the entire community, such as nutritional approaches or faecal microbiota transplantation, while others, such as phage therapy, probiotics, and prebiotics, target specific taxa or strains. In this review, we assessed the experimental evidence for microbiome-based interventions, with a particular focus on their clinical relevance, ecological effects, and modulation of the immune system.}, }
@article {pmid36179888, year = {2023}, author = {Hoshino, E and Moriwaki, K and Morimoto, K and Sakai, K and Shimohata, N and Konomura, K and Urayama, KY and Suzuki, M and Shimozuma, K}, title = {Cost-Effectiveness Analysis of Universal Screening for Biliary Atresia in Japan.}, journal = {The Journal of pediatrics}, volume = {253}, number = {}, pages = {101-106.e2}, doi = {10.1016/j.jpeds.2022.09.028}, pmid = {36179888}, issn = {1097-6833}, mesh = {Infant ; Humans ; Infant, Newborn ; *Biliary Atresia/diagnosis/surgery ; Cost-Effectiveness Analysis ; Japan ; Feces ; Neonatal Screening/methods ; Bilirubin ; Cost-Benefit Analysis ; Mass Screening/methods ; }, abstract = {OBJECTIVE: To evaluate the cost-effectiveness of universal newborn screening using stool color card or direct bilirubin (DB) testing when comparing with no screening for biliary atresia in Japanese setting.<br><br>STUDY DESIGN: A decision analytic Markov microsimulation model was developed to evaluate the universal screening for biliary atresia. Our screening strategies included stool color card, DB, or no screening. The outcomes of all newborns undergoing 3 strategies were simulated to analyze event-free life-years defined as liver transplant-free survival, costs, and incremental cost-effectiveness ratio (ICER) over a 25-year period with an annual discount rate of 2% applied for both costs and outcomes. A 1-way sensitivity analysis was performed to assess the uncertainty.<br><br>RESULTS: There were 941&#x2009;000 newborn infants in our cohort and 114 cases of biliary atresia. The base case analysis showed that the stool color card strategy was $14&#x2009;927&#x2009;337 higher than no screening with an increase in 44 more event-free life-years gained, resulting in an ICER of $339&#x2009;258 per event-free life-year gained. The DB screening strategy compared with stool color card was $138&#x2009;994&#x2009;060 higher with an increase in 271 more event-free life-years gained and an ICER of $512&#x2009;893 per event-free life-year gained. The DB screening strategy compared with no screening resulted in an ICER of $488&#x2009;639 per event-free life-year gained. The DB screening resulted in 16 fewer liver transplants than stool color card and stool color card had 2 fewer liver transplants than no screening.<br><br>CONCLUSIONS: Universal screening for biliary atresia could be cost-effective depending on the willingness to pay thresholds for health benefits.}, }
@article {pmid36179877, year = {2023}, author = {Liang, J and Zhang, M and Wang, H and Ren, Y and Wu, Q and Huang, R and Xie, J and Yin, J and Zhu, J}, title = {Cholestyramine resin administration alleviated cerebral ischemic injury in obese mice by improving gut dysbiosis and modulating the bile acid profile.}, journal = {Experimental neurology}, volume = {359}, number = {}, pages = {114234}, doi = {10.1016/j.expneurol.2022.114234}, pmid = {36179877}, issn = {1090-2430}, mesh = {Mice ; Animals ; Dysbiosis/complications/metabolism ; Mice, Obese ; Bile Acids and Salts ; Cholestyramine Resin/therapeutic use ; *Neuroprotective Agents ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Obesity/complications ; *Stroke/complications ; *Brain Injuries/complications ; }, abstract = {Obesity is a risk factor for cerebrovascular diseases. Accumulating evidence has revealed that gut dysbiosis plays an important role in the pathophysiology of cerebrovascular diseases. However, little is known about the role of gut dysbiosis in stroke in obesity. In this study, we established a rodent middle cerebral artery occlusion (MCAO) model to investigate whether obesity-induced gut dysbiosis exacerbates cerebral ischemic injury and the role of the bile salt sequestrant cholestyramine resin (CR) in gut microbiota and stroke outcome in obese mice. Long-term 45% high-fat diet (HFD) diet (8 weeks) induced an obesity phenotype and caused gut dysbiosis, resulting in a larger infarct volume and higher serum levels of inflammatory cytokines after stroke, compared to those in the lean counterparts. LC-MS/MS and GC analysis revealed that obese mice with stroke developed an obviously perturbed bile acid (BA) profile characterized by higher levels of deoxycholic acid and its conjugated forms, and lower levels of butyrate in the cecal content. CR administration improved the obesity-induced dysbiotic microbiome, attenuated ischemic brain injury and modulated the stroke-perturbed BA profile. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that the impact of obesity on stroke and the neuroprotective effects of CR were mediated by gut microbiota. In conclusion, Obesity induces gut dysbiosis, worsens stroke outcomes, and perturbs the BA profile. The dysbiotic microbiome is an important linkage between obesity and stroke. CR confers metabolic benefits and neuroprotective effects in obesity, perhaps by modulating gut microbial composition and BA metabolism.}, }
@article {pmid36178211, year = {2023}, author = {Yao, S and Yagi, S and Hirata, M and Miyachi, Y and Ogawa, E and Uozumi, R and Sugimoto, T and Asahara, T and Uemoto, S and Hatano, E}, title = {Chronological changes in the gut microbiota and intestinal environment in recipients and donors of living donor liver transplantation.}, journal = {Journal of hepato-biliary-pancreatic sciences}, volume = {30}, number = {4}, pages = {439-452}, doi = {10.1002/jhbp.1241}, pmid = {36178211}, issn = {1868-6982}, support = {//Fujiwara Memorial Foundation/ ; 18K08567//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Liver Transplantation ; Living Donors ; *Gastrointestinal Microbiome ; *End Stage Liver Disease/surgery ; Prospective Studies ; Severity of Illness Index ; }, abstract = {BACKGROUND/PURPOSE: This prospective study aimed to investigate the dynamic changes in the gut microbiota (GM) and associated intestinal environment, which were assessed by measuring fecal organic acid (OA) concentrations, during the early period after liver transplantation (LT). To understand the fundamental characteristics of the human GM, data obtained from living donors were also analyzed.<br><br>METHODS: Fixed-point observation was performed in 23 recipients and 21 donors for up to 2&#x2009;weeks after LT. The GM and OA concentrations were investigated using ribosomal RNA-targeted reverse-transcription quantitative polymerase chain reaction and high-performance liquid chromatography, respectively.<br><br>RESULTS: Before LT, the recipients exhibited remarkable dysbiosis and OA depletion, which were proportional to the model for end-stage liver disease score. Correlations between the abundances of some specific strains and OA concentrations were observed. After LT, while donor lobectomy caused only slight, transient and reversible changes in the GM and OA concentrations, recipients exhibited delayed recovery in these factors. However, no clear evidence of causality was observed between the GM or OA concentrations and LT outcomes.<br><br>CONCLUSIONS: The GM and intestinal environment in LT recipients exhibited characteristics that were clearly different from those in donors. LT did not normalize but rather disrupted the GM during the early post-LT period, but its negative clinical impact could be minimized with perioperative management.}, }
@article {pmid36178158, year = {2022}, author = {Rudiansyah, M and Abdalkareem Jasim, S and S Azizov, B and Samusenkov, V and Kamal Abdelbasset, W and Yasin, G and Mohammad, HJ and Jawad, MA and Mahmudiono, T and Hosseini-Fard, SR and Mirzaei, R and Karampoor, S}, title = {The emerging microbiome-based approaches to IBD therapy: From SCFAs to urolithin A.}, journal = {Journal of digestive diseases}, volume = {23}, number = {8-9}, pages = {412-434}, doi = {10.1111/1751-2980.13131}, pmid = {36178158}, issn = {1751-2980}, mesh = {Adult ; Child ; Humans ; *Inflammatory Bowel Diseases/pathology ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy/complications ; }, abstract = {Inflammatory bowel disease (IBD) is a group of chronic gastrointestinal inflammatory conditions which can be life-threatening, affecting both children and adults. Crohn's disease and ulcerative colitis are the two main forms of IBD. The pathogenesis of IBD is complex and involves genetic background, environmental factors, alteration in gut microbiota, aberrant immune responses (innate and adaptive), and their interactions, all of which provide clues to the identification of innovative diagnostic or prognostic biomarkers and the development of novel treatments. Gut microbiota provide significant benefits to its host, most notably via maintaining immunological homeostasis. Furthermore, changes in gut microbial populations may promote immunological dysregulation, resulting in autoimmune diseases, including IBD. Investigating the interaction between gut microbiota and immune system of the host may lead to a better understanding of the pathophysiology of IBD as well as the development of innovative immune- or microbe-based therapeutics. In this review we summarized the most recent findings on innovative therapeutics for IBD, including microbiome-based therapies such as fecal microbiota transplantation, probiotics, live biotherapeutic products, short-chain fatty acids, bile acids, and urolithin A.}, }
@article {pmid36177467, year = {2022}, author = {Hu, L and Li, G and Shu, Y and Hou, X and Yang, L and Jin, Y}, title = {Circadian dysregulation induces alterations of visceral sensitivity and the gut microbiota in Light/Dark phase shift mice.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {935919}, pmid = {36177467}, issn = {1664-302X}, abstract = {BACKGROUND: It is well-established that several features of modern lifestyles, such as shift work, jet lag, and using electronics at night, disturb normal circadian rhythm and increase the risk of suffering from functional gastrointestinal disease. Although substantial evidence demonstrates that shift work is closely correlated with the symptoms of visceral hypersensitivity, few basic studies have revealed the mechanism of visceral hypersensitivity induced by circadian rhythm disturbance, especially light/dark phase shifts. Our study explored the mechanism underlying visceral hypersensitivity caused by light/dark phase shift in mice.<br><br>METHODS: A 6-h delay light/dark phase shift mice model was constructed. Visceral hypersensitivity was assessed by abdominal withdrawal reflex (AWR) score induced by colorectal distention (CRD) in vivo and contraction of colonic muscle strips induced by acetylcholine ex vivo. Intestinal permeability was evaluated by transepithelial resistance (TEER) and FD4 permeability. The expression of tight junction proteins was detected by western blotting and immunofluorescence staining. The gut microbiota was examined by 16S rDNA sequencing. Fecal microbiota transplantation (FMT) was performed to confirm the relationship between the light/dark phase shift, gut microbiota, and visceral hypersensitivity.<br><br>RESULTS: We found that light/dark phase shift increased visceral sensitivity and disrupted intestinal barrier function, caused low-grade intestinal inflammation. Moreover, we found decreased microbial species richness and diversity and a shift in microbial community with a decreased proportion of Firmicutes and an elevated abundance of Proteobacteria at the phylum level. Besides, after the light/dark phase shift, the microflora was significantly enriched in biosynthesizing tryptophan, steroid hormone, secondary metabolites, lipids, and lipopolysaccharides. Mice that underwent FMT from the light/dark phase shift mice model exhibited higher visceral hypersensitivity and worse barrier function. Dysbiosis induced by light/dark phase shift can be transmitted to the mice pretreated with antibiotics by FMT not only at the aspect of microbiota composition but also at the level of bacterial function.<br><br>CONCLUSION: Circadian rhythm disturbance induced by the light/dark phase shift produces visceral hypersensitivity similar to the pathophysiology of IBS through modulating the gut microbiota, which may disrupt intestinal barrier function or induce a low-degree gut inflammation.}, }
@article {pmid36177048, year = {2022}, author = {Hazime, R and Eddehbi, FE and El Mojadili, S and Lakhouaja, N and Souli, I and Salami, A and M'Raouni, B and Brahim, I and Oujidi, M and Guennouni, M and Bousfiha, AA and Admou, B}, title = {Inborn errors of immunity and related microbiome.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {982772}, pmid = {36177048}, issn = {1664-3224}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Immune System Diseases/genetics/microbiology ; Immunoglobulin A ; Receptors, Interleukin-10 ; }, abstract = {Inborn errors of immunity (IEI) are characterized by diverse clinical manifestations that are dominated by atypical, recurrent, chronic, or severe infectious or non-infectious features, including autoimmunity, lymphoproliferative disease, granulomas, and/or malignancy, which contribute substantially to morbidity and mortality. Some data suggest a correlation between clinical manifestations of IEI and altered gut microbiota. Many IEI display microbial dysbiosis resulting from the proliferation of pro-inflammatory bacteria or a decrease in anti-inflammatory bacteria with variations in the composition and function of numerous microbiota. Dysbiosis is considered more established, mainly within common variable immunodeficiency, selective immunoglobulin A deficiency, severe combined immunodeficiency diseases, Wiskott-Aldrich syndrome, Hyper-IgE syndrome, autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED), immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, IL-10 receptor deficiency, chronic granulomatous disease, and Kostmann disease. For certain IEIs, the specific predominance of gastrointestinal, respiratory, and cutaneous involvement, which is frequently associated with dysbiosis, justifies the interest for microbiome identification. With the better understanding of the relationship between gut microbiota, host immunity, and infectious diseases, the integration of microbiota modulation as a therapeutic approach or a preventive measure of infection becomes increasingly relevant. Thus, a promising strategy is to develop optimized prebiotics, probiotics, postbiotics, and fecal microbial transplantation to rebalance the intestinal microbiota and thereby attenuate the disease activity of many IEIs.}, }
@article {pmid36177041, year = {2022}, author = {Xu, H and Cao, C and Ren, Y and Weng, S and Liu, L and Guo, C and Wang, L and Han, X and Ren, J and Liu, Z}, title = {Antitumor effects of fecal microbiota transplantation: Implications for microbiome modulation in cancer treatment.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {949490}, pmid = {36177041}, issn = {1664-3224}, mesh = {Dysbiosis/therapy ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Humans ; Immune Checkpoint Inhibitors ; *Microbiota/physiology ; *Neoplasms/therapy ; }, abstract = {Fecal microbiome transplantation (FMT) from healthy donors is one of the techniques for restoration of the dysbiotic gut, which is increasingly being used to treat various diseases. Notably, mounting evidence in recent years revealed that FMT has made a breakthrough in the oncology treatment area, especially by improving immunotherapy efficacy to achieve antitumor effects. However, the mechanism of FMT in enhancing antitumor effects of immune checkpoint blockers (ICBs) has not yet been fully elucidated. This review systematically summarizes the role of microbes and their metabolites in the regulation of tumor immunity. We highlight the mechanism of action of FMT in the treatment of refractory tumors as well as in improving the efficacy of immunotherapy. Furthermore, we summarize ongoing clinical trials combining FMT with immunotherapy and further focus on refined protocols for the practice of FMT in cancer treatment, which could guide future directions and priorities of FMT scientific development.}, }
@article {pmid36176029, year = {2022}, author = {Shen, Q and Huang, Z and Ma, L and Yao, J and Luo, T and Zhao, Y and Xiao, Y and Jin, Y}, title = {Extracellular vesicle miRNAs promote the intestinal microenvironment by interacting with microbes in colitis.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2128604}, pmid = {36176029}, issn = {1949-0984}, mesh = {Animals ; Bacteria/genetics ; *Colitis/chemically induced/microbiology ; Dextran Sulfate ; Disease Models, Animal ; *Extracellular Vesicles ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases ; Intestines ; *MicroRNAs/genetics ; *Microbiota ; }, abstract = {Inflammatory bowel disease (IBD) is a global disease with no cure. Disruption of the microbial ecosystem is considered to be an important cause of IBD. Extracellular vesicles (EVs) are vital participants in cell-cell and cell-organism communication. Both host-derived EVs and bacteria-derived membrane vesicles (OMVs) contribute to homeostasis in the intestine. However, the roles of EVs-miRNAs and MVs in host-microbe interactions in colitis remain unclear. In the present study, the animal model of colitis was established by dextran sulfate sodium (DSS) to investigate the changes of miRNAs in colonic EVs from colitis. Several miRNAs were significantly altered in colitis EVs. miR-181b-5p transplantation inhibited M1 macrophage polarization and promoted M2 polarization to reduce the levels of inflammation both in acute and remission of chronic colitis. miR-200b-3p could interact with bacteria and regulate the composition of the microbiota, which contributed to intestinal barrier integrity and homeostasis. Notably, MVs from normal feces could effectively reverse the composition of the intestinal microbiota, restore the intestinal barrier and rescue colitis, and BMVs from colitis would also have similar effects after miR-200b-3p treatment. Our results preliminarily identify a vesicle-based host-microbe interaction cycle in colitis and provide new ideas for colitis treatment.}, }
@article {pmid36175995, year = {2022}, author = {Carpén, N and Brodin, P and de Vos, WM and Salonen, A and Kolho, KL and Andersson, S and Helve, O}, title = {Transplantation of maternal intestinal flora to the newborn after elective cesarean section (SECFLOR): study protocol for a double blinded randomized controlled trial.}, journal = {BMC pediatrics}, volume = {22}, number = {1}, pages = {565}, pmid = {36175995}, issn = {1471-2431}, mesh = {Cesarean Section/adverse effects ; Child, Preschool ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Intestines ; Milk, Human ; Pregnancy ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: A complication of elective cesarean section (CS) delivery is its interference with the normal intestinal colonization of the infant, affecting the immune and metabolic signaling in early life- a process that has been associated with long-term morbidity, such as allergy and diabetes. We evaluate, in CS-delivered infants, whether the normal intestinal microbiome and its early life development can be restored by immediate postnatal transfer of maternal fecal microbiota (FMT) to the newborn, and how this procedure influences the maturation of the immune system.<br><br>METHODS: Sixty healthy mothers with planned elective CS are recruited and screened thoroughly for infections. A maternal fecal sample is taken prior to delivery and processed according to a transplantation protocol. After double blinded randomization, half of the newborns will receive a diluted aliquot of their own mother's stool orally administered in breast milk during the first feeding while the other half will be similarly treated with a placebo. The infants are clinically followed, and fecal samples are gathered weekly until the age of 4&#xa0;weeks, then at the ages of 8&#xa0;weeks, 3, 6, 12 and 24&#xa0;months. The parents fill in questionnaires until the age of 24&#xa0;months. Blood samples are taken at the age of 2-3&#xa0;days and 3, 6, 12 and 24&#xa0;months to assess development of major immune cell populations and plasma proteins throughout the first years of life.<br><br>DISCUSSION: This is the first study to assess long-time effects on the intestinal microbiome and the development of immune system of a maternal fecal transplant given to term infants born by CS.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT04173208 , registration date 21.11.2019.}, }
@article {pmid36175620, year = {2022}, author = {Eaton, SE and Kaczmarek, J and Mahmood, D and McDiarmid, AM and Norarfan, AN and Scott, EG and Then, CK and Tsui, HY and Kiltie, AE}, title = {Exploiting dietary fibre and the gut microbiota in pelvic radiotherapy patients.}, journal = {British journal of cancer}, volume = {127}, number = {12}, pages = {2087-2098}, pmid = {36175620}, issn = {1532-1827}, mesh = {Humans ; *Dietary Fiber ; *Neoplasms ; }, abstract = {With an ageing population, there is an urgent need to find alternatives to current standard-of-care chemoradiation schedules in the treatment of pelvic malignancies. The gut microbiota may be exploitable, having shown a valuable role in improving patient outcomes in anticancer immunotherapy. These bacteria feed on dietary fibres, which reach the large intestine intact, resulting in the production of beneficial metabolites, including short-chain fatty acids. The gut microbiota can impact radiotherapy (RT) treatment responses and itself be altered by the radiation. Evidence is emerging that manipulation of the gut microbiota by dietary fibre supplementation can improve tumour responses and reduce normal tissue side effects following RT, although data on tumour response are limited to date. Both may be mediated by immune and non-immune effects of gut microbiota and their metabolites. Alternative approaches include use of probiotics and faecal microbiota transplantation (FMT). Current evidence will be reviewed regarding the use of dietary fibre interventions and gut microbiota modification in improving outcomes for pelvic RT patients. However, data regarding baseline (pre-RT) gut microbiota of RT patients and timing of dietary fibre manipulation (before or during RT) is limited, heterogenous and inconclusive, thus more robust clinical studies are required before these strategies can be applied clinically.}, }
@article {pmid36175117, year = {2023}, author = {Liu, Q and Cammarota, G and Ianiro, G}, title = {Evaluating microbial determinants of donor efficacy to translate faecal microbiota transplantation from research to clinical practice.}, journal = {Gut}, volume = {72}, number = {1}, pages = {5-7}, doi = {10.1136/gutjnl-2022-328573}, pmid = {36175117}, issn = {1468-3288}, mesh = {Humans ; *Fecal Microbiota Transplantation ; Feces ; *Inflammatory Bowel Diseases ; }, }
@article {pmid36174640, year = {2022}, author = {Malard, F and Gaugler, B and Mohty, M}, title = {Faecal microbiota transplantation in patients with haematological malignancies undergoing cellular therapies: from translational research to routine clinical practice.}, journal = {The Lancet. Haematology}, volume = {9}, number = {10}, pages = {e776-e785}, doi = {10.1016/S2352-3026(22)00223-X}, pmid = {36174640}, issn = {2352-3026}, mesh = {Cell- and Tissue-Based Therapy ; Fecal Microbiota Transplantation/adverse effects ; *Graft vs Host Disease/etiology ; *Hematologic Neoplasms/therapy ; Humans ; Translational Research, Biomedical ; }, abstract = {The effect of the gut microbiota on patients' outcomes after allogeneic haematopoietic cell transplantation (HCT) is now well established. In particular, gut microbiota dysbiosis has been associated with acute graft-versus-host disease (GVHD). Furthermore, increasing data also suggest an effect of the gut microbiota on outcome after autologous HCT and CAR T cells. In fact, the bacterial gut microbiota interplays with the immune system and contributes to immunological complication and antitumour response to treatment. Therefore, faecal microbiota transplantation has been evaluated in patients with haematological malignancies for various indications, including Clostridioides difficile infection, eradication of multidrug-resistant bacteria, and steroid refractory acute GVHD. In addition, use of prophylactic faecal microbiota transplantation to restore the gut microbiota and improve patients' outcomes is being developed in the setting of allogeneic HCT, but also probably very soon in patients receiving autologous HCT or CAR T cells.}, }
@article {pmid36172516, year = {2022}, author = {Lin, X and Zhou, R and Liang, D and Xia, L and Zeng, L and Chen, X}, title = {The role of microbiota in autism spectrum disorder: A bibliometric analysis based on original articles.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {976827}, pmid = {36172516}, issn = {1664-0640}, abstract = {BACKGROUND: Gastrointestinal (GI) symptoms can be observed in autism spectrum disorder (ASD) children. It is suggested that the gut microbiota and its metabolites are associated, not only with GI symptoms, but also with behaviors of ASD. The aim of this study was to explore the development context, research hotspots and frontiers of gut microbiota and ASD from January 1, 1980 to April 1, 2022 by bibliometric analysis.<br><br>MATERIALS AND METHODS: Publications of ASD and gut microbiota research from 1 January 1980 to 1 April 2022 were retrieved from the Web of Science Core Collection (WoSCC). Publications and citations trends were analyzed by Excel 2010. CiteSpace was used to analyze countries/regions, authors, institutes, references, and keywords and to visualize the knowledge map.<br><br>RESULTS: A total of 1027 studies were retrieved, and 266 original articles were included after screening. The most published countries and institutes were the United States and King Saud University. Afaf El-Aansary published the most articles, while Finegold SM had the highest co-citations. Hotspots and emerging trends in this area may be indicated by co-cited references and keywords and their clusters, including "gut-brain axis," "behavior," "chain fatty acid," "brain," "feces," "propionic acid," "clostridium perfringens," and "species clostridium innocuum."<br><br>CONCLUSION: The United States dominants the research in this field, which focuses on the alterations of gut microbiota composition and its metabolites, among which the roles of the genus Clostridium and metabolites of short-chain fatty acids, especially propionic acid, are priorities. Fecal microbiota transplantation (FMT) is a promising complementary therapy. In general, research in this area is sparse, but it still has great research prospects.}, }
@article {pmid36171751, year = {2022}, author = {Meng, Y and Feng, Y and Hang, L and Zhou, Y and Wang, E and Yuan, J}, title = {No synergistic effect of fecal microbiota transplantation and shugan decoction in water avoidance stress-induced IBS-D rat model.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {995567}, pmid = {36171751}, issn = {1664-302X}, abstract = {BACKGROUND: It has been reported that 5-hydroxytryptamine (5-HT, serotonin) metabolism is involved in the pathogenesis of irritable bowel syndrome (IBS) and that either Shugan decoction (SGD) or fecal microbiota transplantation (FMT) can alleviate the symptoms of IBS in patients and animal models. But the synergistic effect of FMT and SGD on 5-HT metabolism and IBS symptoms has not been investigated.<br><br>AIM: The main purpose of this study is to observe the synergistic effect of FMT with SGD on symptoms and 5-HT metabolism in IBS-D rats induced by water avoidance stress (WAS). Moreover, the possible material basis of the FMT was investigated.<br><br>METHODS: In experiment I, rats were randomly divided into seven groups. Control group: routine feeding; WAS&#x2192; Control group: routine feeding with fecal microbiota liquid (FML) 1 (derived from rats in WAS group) gavage since the fourth day; WAS group: 10 days WAS with routine feeding; SGD group: 10 days WAS with SGD gavage since the fourth day on the base of routine feeding; Control&#x2192; WAS group: 10 days WAS with FML2 (derived from rats in Control group) gavage since the fourth day with routine feeding; SGD&#x2192; WAS group: 10 days WAS with FML3 (derived from rats in SGD group) gavage since the fourth day with routine feeding; SGD + (Control&#x2192; WAS) group: 10 days WAS with SGD and FML2 (derived from rats in Control group) gavage since the fourth day with routine feeding. In experiment II, rats were randomly divided into three groups. Control group: routine feeding; Control&#x2192; WAS group: 10 days WAS with FML2 gavage since the fourth day with routine feeding; FControl&#x2192; WAS group: 10 days WAS with FML2 filtrate gavage since the fourth day. The number of fecal pellets output (FPT) and the pain pressure threshold (PPT) were recorded. The histological changes in colon mucosa were observed by hematoxylin-eosin (HE) stain. The number of enterochromaffin cells (ECs), the content of 5-HT, and the expression of serotonin reuptake transporter (SERT) protein in the colon were measured by immunofluorescence or western blotting.<br><br>RESULTS: Compared with that in the control group, the PPT and the expression of SERT in the WAS group and that in the WAS&#x2192; Control group were decreased with the increased number of ECs and the level of 5-HT in colon. But the FPT was not increased in the WAS&#x2192; Control group although that was increased in the WAS group. Compared with that in the WAS group, the FPT, the PPT, the number of ECs, the level of 5-HT, and the expression of SERT protein in colon in the SGD group, control&#x2192; WAS group, SGD&#x2192; WAS group, and SGD+(Control&#x2192; WAS) group were all recovered. The recovery of these indicators in the Control&#x2192; WAS group and that in the FControl&#x2192; WAS group was not significantly different.<br><br>CONCLUSION: No synergistic effect of SGD with FMT on IBS symptoms induced by WAS was found. The metabolites of intestinal microbiota may be the main active substances of the FML derived from normal rats to alleviate WAS-induced IBS symptoms.}, }
@article {pmid36168377, year = {2022}, author = {Ramesh, AS and Munoz Tello, C and Jamil, D and Tran, HH and Mansoor, M and Butt, SR and Satnarine, T and Ratna, P and Sarker, A and Khan, S}, title = {Role of Fecal Microbiota Transplantation in Reducing Clostridioides difficile Infection-Associated Morbidity and Mortality: A Systematic Review.}, journal = {Cureus}, volume = {14}, number = {8}, pages = {e28402}, pmid = {36168377}, issn = {2168-8184}, abstract = {Clostridioides difficile (C. difficile) is a gram-positive, anaerobic, spore-forming bacterium that produces toxins A and B, disrupting the intestinal brush border and resulting in severe diarrhea. The most common causes of infection include prolonged antibiotic use, proton pump inhibitors (PPIs), and long-term hospitalization resulting in complications such as pseudomembranous colitis and toxic megacolon. This systematic review aims to consider fecal microbiota transplantation (FMT) as an early treatment modality in C. difficile infection to prevent complications and reduce related morbidity and mortality. We systematically screened three databases using regular keywords such as "fecal microbiota transplantation," "C. difficile," "pseudomembranous colitis," and "toxic megacolon" and Medical Subject Headings (MeSH) terms. We applied the inclusion and exclusion criteria and performed a thorough quality appraisal using standardized checklists. We were finally left with 10 articles, including seven case reports, one case series, and two observational studies. Questions remain as to the route of administration of FMT, timing, safety, availability, and the number of sittings required. More randomized controlled trials are needed to address all these questions and to assess the safety of FMT. We believe the role of FMT is very important as it can prevent C. difficile related complications and would be an ideal treatment option in a population group that is often unfit for surgical management.}, }
@article {pmid36167905, year = {2023}, author = {Qiao, X and Biliński, J and Wang, L and Yang, T and Luo, R and Fu, Y and Yang, G}, title = {Safety and efficacy of fecal microbiota transplantation in the treatment of graft-versus-host disease.}, journal = {Bone marrow transplantation}, volume = {58}, number = {1}, pages = {10-19}, pmid = {36167905}, issn = {1476-5365}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; *Graft vs Host Disease/therapy/etiology ; Prospective Studies ; Retrospective Studies ; Steroids ; Treatment Outcome ; }, abstract = {This article evaluates the efficacy and safety of FMT in the treatment of GVHD after HSCT using a systematic literature search to conduct a meta-analysis constructed of studies involving GVHD patients treated with FMT. 23 studies were included, among which 2 prospective cohort studies, 10 prospective single arm studies, 2 retrospective single arm studies, 2 case series and 7 case reports, comprise a total of 242 patients with steroid-resistant or steroid-dependent GVHD secondary to HSCT who were treated with FMT. 100 cases achieved complete responses, while 61 cases showed partial responses, and 81 cases presented no effect after FMT treatment. The estimate of clinical remission odds ratio was 5.51 (95% CI 1.49-20.35) in cohort studies, and the pooled clinical remission rate is 64% (51-77%) in prospective single arm studies and 81% (62-95%) in retrospective studies, case series and case reports. Five (2.1%) patients had FMT-related infection events, but all recovered after treatment. Other adverse effects were mild and acceptable. Microbiota diversity and composition, donor type, and other related issues were also analyzed. The data proves that FMT is a promising treatment modality of GVHD, but further validation of its safety and efficacy is still needed with prospective control studies.Clinical trial registration: Registered in https://www.crd.york.ac.uk/PROSPERO/ CRD42022296288.}, }
@article {pmid36165762, year = {2023}, author = {Zhou, H and Yu, B and Sun, J and Chen, H and Liu, Z and Ge, L and Chen, D}, title = {Comparison of maternal and neonatal gut microbial community and function in a porcine model.}, journal = {Animal biotechnology}, volume = {34}, number = {7}, pages = {2972-2978}, doi = {10.1080/10495398.2022.2126367}, pmid = {36165762}, issn = {1532-2378}, mesh = {Humans ; Swine ; Animals ; Female ; *Microbiota ; *Gastrointestinal Microbiome ; Feces ; Bacteria ; *Lactobacillales ; }, abstract = {Our knowledge of the difference in maternal and neonatal gut microbiota composition is not fully understood. Using the Bama miniature pig model, the bacterial community in the feces from sows and piglets was analyzed on an IonS5TMXL platform targeting the single-end reads strategy. Results revealed that the maternal and neonatal bacteria profile in the pig model was distinct. Compared with the piglets, sows had higher proportions of bacteria in Spirochetes, Clostridiales, and Spirochaetales (p < 0.10) and had a lower abundance of bacteria in Tyzzerella (p < 0.05) and Alistipes (p < 0.10). Meanwhile, the proportions of bacteria in Oscillibacter and the index of Chao1, Shannon, and observed_species increased in the sows compared with those in the piglets (p < 0.05). Moreover, the abundance of bacteria associated with the human disease was higher (p < 0.05) and the population of bacteria associated with cellular processes was lower (p < 0.05) in the piglets compared with those in the sows. Collectively, the diversity and beneficial bacteria populations in the sow fecal microbiota exhibit more than those in the piglets. This study indicates that maternal fecal microbiota may be a beneficial source of transplanted bacteria to promote healthy function in neonates.}, }
@article {pmid36164761, year = {2022}, author = {Hooi, SL and Dwiyanto, J and Rasiti, H and Toh, KY and Wong, RKM and Lee, JWJ}, title = {A case report of improvement on ADHD symptoms after fecal microbiota transplantation with gut microbiome profiling pre- and post-procedure.}, journal = {Current medical research and opinion}, volume = {38}, number = {11}, pages = {1977-1982}, doi = {10.1080/03007995.2022.2129232}, pmid = {36164761}, issn = {1473-4877}, mesh = {Female ; Humans ; Young Adult ; Adult ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Clostridioides difficile ; *Attention Deficit Disorder with Hyperactivity/therapy ; *Clostridium Infections ; Feces ; }, abstract = {BACKGROUND: Recent studies demonstrate the association of the gut microbiome in regulating interactions between the central nervous system and intestinal function. Individuals with attention-deficit hyperactivity disorder (ADHD) have been shown to have unique gut microbial signature, with depletion of beneficial commensal microbes. Fecal microbiota transplant (FMT) restores the imbalanced gut microbiome and may replete missing microbes to increase production of hormones and neurotransmitters regulating human behavior and cognition.<br><br>RESEARCH DESIGN &amp; METHODS: Here, we present an interesting case of a 22-year-old woman treated with FMT primarily to treat recurrent Clostridioides difficile infection, which coincidentally alleviated her ADHD symptoms. We also present the pre- and post-FMT gut microbiota profiles conducted using shotgun metagenomic sequencing on the patient's fecal samples to thereby highlight potential microbial-associated mechanisms associated with the relief of ADHD symptoms.<br><br>RESULTS &amp; CONCLUSIONS: Our case report provides preliminary evidence regarding the use of FMT in a patient with C. difficile and ADHD. We speculate that gut microbiome modulation, in particular the gain or loss of specific microbial species and pathways involving the metabolism of SCFAs, tryptophan and GABA, may merit further exploration as a potential therapeutic strategy for ADHD.}, }
@article {pmid36162378, year = {2022}, author = {Pasokh, A and Farzipour, M and Mahmoudi, J and Sadigh-Eteghad, S}, title = {The effect of fecal microbiota transplantation on stroke outcomes: A systematic review.}, journal = {Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association}, volume = {31}, number = {11}, pages = {106727}, doi = {10.1016/j.jstrokecerebrovasdis.2022.106727}, pmid = {36162378}, issn = {1532-8511}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; Feces ; *Gastrointestinal Microbiome ; }, abstract = {BACKGROUND AND PURPOSE: Fecal microbiota transplantation (FMT) is a novel microbiota-based therapeutic method that transfers stool from donor into a recipient and its application is under investigating for neurological disorders such as stroke. In this systematic review, we assessed the effect of FMT in progression and treatment of stroke and recovery of post-stroke complications.<br><br>METHODS: Preliminary studies were searched in MEDLINE via PubMed, Scopus, COCHRANE library and Google Scholar, databases up to February 2022. The search strategy was restricted to articles about FMT in stroke. The initial search yielded 4570 articles, of which 19 publications were included in our systematic review.<br><br>RESULTS: Based on outcomes transferring microbiome from healthy or ischemic donor to other ischemic recipient can affect brain infarct volume and survival rate, neurological and behavioral outcomes, and inflammatory pathways.<br><br>CONCLUSIONS: Our systematic review on preclinical studies showed that manipulating gut microbiota via FMT can be a possible therapeutic approach for treatment of stroke and recovery of post-stroke complications.}, }
@article {pmid36161997, year = {2022}, author = {Gill, VJS and Soni, S and Shringarpure, M and Anusheel,  and Bhardwaj, S and Yadav, NK and Patel, A and Patel, A}, title = {Gut Microbiota Interventions for the Management of Obesity: A Literature Review.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e29317}, pmid = {36161997}, issn = {2168-8184}, abstract = {The gut microbiota (GM) has been recognized as an important factor in the development of metabolic diseases such as obesity; it has been reported that the composition of the GM differs in obese and lean subjects, suggesting that microbiota dysbiosis can contribute to changes in body weight. Dysbiosis occurs due to an imbalance in the composition of gut bacteria, changes in the metabolic process, or changes in the distribution of microbiota within the gut. Dysbiosis can change the functioning of the intestinal barrier and the gut-associated lymphoid tissues (GALT). Microbial manipulation may help with preventing or treating weight gain and associated comorbidities. Approaches to this may range from dietary manipulation, which is suitable to treat the individual's microflora, to probiotics, prebiotics, synbiotics, and fecal microbiota transplant (FMT).}, }
@article {pmid36161939, year = {2022}, author = {Gomez-Nguyen, A and Gupta, N and Sanaka, H and Gruszka, D and Pizarro, A and DiMartino, L and Basson, A and Menghini, P and Osme, A and DeSalvo, C and Pizarro, T and Cominelli, F}, title = {Chronic stress induces colonic tertiary lymphoid organ formation and protection against secondary injury through IL-23/IL-22 signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {40}, pages = {e2208160119}, pmid = {36161939}, issn = {1091-6490}, support = {R01 DK042191/DK/NIDDK NIH HHS/United States ; T32 DK083251/DK/NIDDK NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Colitis ; *Crohn Disease ; Cytokines ; Dextran Sulfate/toxicity ; Dextrans ; Disease Models, Animal ; Inflammation ; Interleukin-23 ; Mice ; Mice, Knockout ; Phenylmercury Compounds ; }, abstract = {Psychological stress has been previously reported to worsen symptoms of inflammatory bowel disease (IBD). Similarly, intestinal tertiary lymphoid organs (TLOs) are associated with more severe inflammation. While there is active debate about the role of TLOs and stress in IBD pathogenesis, there are no studies investigating TLO formation in the context of psychological stress. Our mouse model of Crohn's disease-like ileitis, the SAMP1/YitFc (SAMP) mouse, was subjected to 56 consecutive days of restraint stress (RS). Stressed mice had significantly increased colonic TLO formation. However, stress did not significantly increase small or large intestinal inflammation in the SAMP mice. Additionally, 16S analysis of the stressed SAMP microbiome revealed no genus-level changes. Fecal microbiome transplantation into germ-free SAMP mice using stool from unstressed and stressed mice replicated the behavioral phenotype seen in donor mice. However, there was no difference in TLO formation between recipient mice. Stress increased the TLO formation cytokines interleukin-23 (IL-23) and IL-22 followed by up-regulation of antimicrobial peptides. SAMP × IL-23r[-/-] (knockout [KO]) mice subjected to chronic RS did not have increased TLO formation. Furthermore, IL-23, but not IL-22, production was increased in KO mice, and administration of recombinant IL-22 rescued TLO formation. Following secondary colonic insult with dextran sodium sulfate, stressed mice had reduced colitis on both histology and colonoscopy. Our findings demonstrate that psychological stress induces colonic TLOs through intrinsic alterations in IL-23 signaling, not through extrinsic influence from the microbiome. Furthermore, chronic stress is protective against secondary insult from colitis, suggesting that TLOs may function to improve the mucosal barrier.}, }
@article {pmid36161855, year = {2022}, author = {Watane, A and Raolji, S and Cavuoto, K and Galor, A}, title = {Microbiome and immune-mediated dry eye: a review.}, journal = {BMJ open ophthalmology}, volume = {7}, number = {1}, pages = {}, pmid = {36161855}, issn = {2397-3269}, support = {R01 EY026174/EY/NEI NIH HHS/United States ; P30 EY014801/EY/NEI NIH HHS/United States ; I01 BX004893/BX/BLRD VA/United States ; R61 EY032468/EY/NEI NIH HHS/United States ; I01 CX002015/CX/CSRD VA/United States ; }, mesh = {Anti-Inflammatory Agents ; *Autoimmune Diseases ; *Dry Eye Syndromes/therapy ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {In this review, we aim to summarise key articles that explore relationships between the gut and ocular surface microbiomes (OSMs) and immune-mediated dry eye. The gut microbiome has been linked to the immune system by way of stimulating or mitigating a proinflammatory or anti-inflammatory lymphocyte response, which may play a role in the severity of autoimmune diseases. Although the 'normal' gut microbiome varies among individuals and demographics, certain autoimmune diseases have been associated with characteristic gut microbiome changes. Less information is available on relationships between the OSM and dry eye. However, microbiome manipulation in multiple compartments has emerged as a therapeutic strategy, via diet, prebiotics and probiotics and faecal microbial transplant, in individuals with various autoimmune diseases, including immune-mediated dry eye.}, }
@article {pmid36161048, year = {2022}, author = {Li, YG and Yu, ZJ and Li, A and Ren, ZG}, title = {Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications: Molecular mechanisms and therapeutic inventions.}, journal = {World journal of gastroenterology}, volume = {28}, number = {28}, pages = {3555-3572}, pmid = {36161048}, issn = {2219-2840}, mesh = {Animals ; Antiviral Agents ; *Gastrointestinal Microbiome ; Hepatitis B virus ; *Hepatitis B, Chronic/complications/therapy ; Humans ; Inventions ; Liver Cirrhosis/complications ; *Liver Neoplasms/complications ; Rifaximin ; }, abstract = {Hepatitis B virus (HBV) has posed a threat to public health, mainly resulting in liver damage. With long-term accumulation of extracellular matrix, patients with chronic hepatitis B are at high risk of developing into liver fibrosis and cirrhosis and even life-threatening hepatic carcinoma. The occurrence of complications such as spontaneous bacterial peritonitis and hepatic encephalopathy greatly increases disability and mortality. With deeper understanding of the bidirectional interaction between the liver and the gut (gut-liver axis), there is a growing consensus that the human health closely relates to the gut microbiota. Supported by animal and human studies, the gut microbiota alters as the HBV-related liver fibrosis initials and progresses, characterized as the decrease of the ratio between "good" and "potentially pathogenic" microbes. When the primary disease is controlled via antiviral treatment, the gut microbiota dysfunction tends to be improved. Conversely, the recovery of gut microbiota can promote the regression of liver fibrosis. Therapeutic strategies targeted on gut microbiota (rifaximin, probiotics, engineered probiotics and fecal microbiota transplantation) have been applied to animal models and patients, obtaining satisfactory results.}, }
@article {pmid36159503, year = {2022}, author = {Ma, J and Chen, S and Li, Y and Wu, X and Song, Z}, title = {Arbutin improves gut development and serum lipids via Lactobacillus intestinalis.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {948573}, pmid = {36159503}, issn = {2296-861X}, abstract = {Arbutin has been widely studied in whitening, anti-inflammatory, and antioxidant. However, the interaction between arbutin and intestinal microbes has been rarely studied. Thus, mice were treated with arbutin concentrations of 0, 0.1, 0.2, 0.4, and 1 mg/ml. We found that arbutin promoted gut development such as villus length, villus areas, and villus length/crypt depth (L/D). Total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were significantly reduced by low concentrations of arbutin. Importantly, we analyzed the microbial composition in the control and 0.4 mg/ml arbutin group and found that the abundance of Lactobacillus intestinalis (L. intestinalis) was highest and enhanced in arbutin. Further, mice were fed with oral antibiotics and antibiotics + 0.4 mg/ml arbutin and then we transplanted fecal microbes from oral 0.4 mg/ml arbutin mice to mice pretreated with antibiotics. Our results showed that arbutin improves gut development, such as villus width, villus length, L/D, and villus areas. In addition, L. intestinalis monocolonization was carried out after a week of oral antibiotics and increased villus length, crypt depth, and villus areas. Finally, in vitro arbutin and L. intestinalis co-culture showed that arbutin promoted the growth and proliferation of L. intestinalis. Taken together, our results suggest that arbutin improves gut development and health of L. intestinalis. Future studies are needed to explore the function and mechanism of L. intestinalis affecting gut development.}, }
@article {pmid36159020, year = {2022}, author = {Ikeda, Y and Taniguchi, K and Sawamura, H and Tsuji, A and Matsuda, S}, title = {Promising role of D-amino acids in irritable bowel syndrome.}, journal = {World journal of gastroenterology}, volume = {28}, number = {31}, pages = {4471-4474}, pmid = {36159020}, issn = {2219-2840}, mesh = {Amines ; Amino Acids/metabolism/therapeutic use ; Feces ; Fermentation ; *Gastrointestinal Microbiome/physiology ; Humans ; *Irritable Bowel Syndrome ; *Microbiota ; }, abstract = {Irritable bowel syndrome (IBS) is an important health care concern. Alterations in the microbiota of the gut-brain axis may be linked to the pathophysiology of IBS. Some dietary intake could contribute to produce various metabolites including D-amino acids by the fermentation by the gut microbiota. D-amino acids are the enantiomeric counterparts of L-amino acids, in general, which could play key roles in cellular physiological processes against various oxidative stresses. Therefore, the presence of D-amino acids has been shown to be linked to the protection of several organs in the body. In particular, the gut microbiota could play significant roles in the stability of emotion via the action of D-amino acids. Here, we would like to shed light on the roles of D-amino acids, which could be used for the treatment of IBS.}, }
@article {pmid36158925, year = {2022}, author = {Spanu, D and Pretta, A and Lai, E and Persano, M and Donisi, C and Mariani, S and Dubois, M and Migliari, M and Saba, G and Ziranu, P and Pusceddu, V and Puzzoni, M and Astara, G and Scartozzi, M}, title = {Hepatocellular carcinoma and microbiota: Implications for clinical management and treatment.}, journal = {World journal of hepatology}, volume = {14}, number = {7}, pages = {1319-1332}, pmid = {36158925}, issn = {1948-5182}, abstract = {Gut microbiota plays an essential role in host homeostasis. It is involved in several physiological processes such as nutrients digestion and absorption, maintenance of intestinal epithelial barrier integrity and immune system self-tolerance. Especially the gut microbiota is assumed to play a crucial role in many gastrointestinal, pancreatic and liver disorders. Its role in hepatic carcinogenesis is also gaining increasing interest, especially regarding the development of therapeutic strategies. Different studies are highlighting a link between some bacterial strains and liver disease, including hepatocellular carcinoma (HCC). Indeed, HCC represents an interesting field of research in this perspective, due to the gut-liver axis, to the implication of microbiota in the immune system and to the increasing number of immunotherapy agents investigated in this tumour. Thus, the assessment of the role of microbiota in influencing clinical outcome for patients treated with these drugs is becoming of increasing importance. Our review aims to give an overview on the relationship between microbiota and HCC development/progression and treatment. We focus on potential implications on the available treatment strategies and those under study in the various stages of disease. We highlight the pathogenic mechanisms and investigate the underlying molecular pathways involved. Moreover, we investigate the potential prognostic and/or predictive role of microbiota for target therapies, immune checkpoint inhibitors and loco-regional treatment. Finally, given the limitation of current treatments, we analyze the gut microbiota-mediated therapies and its potential options for HCC treatment focusing on fecal microbiota transplantation.}, }
@article {pmid36158494, year = {2022}, author = {Nishida, A and Nishino, K and Ohno, M and Sakai, K and Owaki, Y and Noda, Y and Imaeda, H}, title = {Update on gut microbiota in gastrointestinal diseases.}, journal = {World journal of clinical cases}, volume = {10}, number = {22}, pages = {7653-7664}, pmid = {36158494}, issn = {2307-8960}, abstract = {The human gut is a complex microbial ecosystem comprising approximately 100 trillion microbes collectively known as the "gut microbiota". At a rough estimate, the human gut microbiome contains almost 3.3 million genes, which are about 150 times more than the total human genes present in the human genome. The vast amount of genetic information produces various enzymes and physiologically active substances. Thus, the gut microbiota contributes to the maintenance of host health; however, when healthy microbial composition is perturbed, a condition termed "dysbiosis", the altered gut microbiota can trigger the development of various gastrointestinal diseases. The gut microbiota has consequently become an extremely important research area in gastroenterology. It is also expected that the results of research into the gut microbiota will be applied to the prevention and treatment of human gastrointestinal diseases. A randomized controlled trial conducted by a Dutch research group in 2013 showed the positive effect of fecal microbiota transplantation (FMT) on recurrent Clostridioides difficile infection (CDI). These findings have led to the development of treatments targeting the gut microbiota, such as probiotics and FMT for inflammatory bowel diseases (IBD) and other diseases. This review focuses on the association of the gut microbiota with human gastrointestinal diseases, including CDI, IBD, and irritable bowel syndrome. We also summarize the therapeutic options for targeting the altered gut microbiota, such as probiotics and FMT.}, }
@article {pmid36157139, year = {2022}, author = {Philips, CA and Schnabl, B and Bajaj, JS}, title = {Gut Microbiome and Alcohol-associated Liver Disease.}, journal = {Journal of clinical and experimental hepatology}, volume = {12}, number = {5}, pages = {1349-1359}, pmid = {36157139}, issn = {0973-6883}, support = {P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; }, abstract = {Changes in gut microbiota (GM) may be associated with the causation and progression of multiple liver diseases such as metabolic-associated liver disease, alcohol-associated liver disease (ALD), alcohol-associated hepatitis (AH), primary biliary cholangitis, primary sclerosing cholangitis, autoimmune liver disease, and most importantly, complications of cirrhosis and portal hypertension such as hepatic encephalopathy (HE), infection, and hepatocellular carcinoma. ALD includes simple steatosis, steatohepatitis, AH, cirrhosis, and acute-on-chronic liver failure. Alcohol consumption is associated with GM changes even before ALD development, and continued alcohol intake results in progressive dysbiosis and development of clinical events such as AH, infection, and HE. The composition and function of GM, specific changes in bacterial communities, and the functional metabolism of GM are affected in the spectrum of ALD, as revealed using high-throughput sequencing. It was reported in preliminary studies that modulation of disrupted GM improves adverse clinical events and ameliorates disease progression in ALD. In this review, we exhaustively discuss the preclinical and clinical studies on GM in ALD and critically discuss GM modulation and its effects based on various human and animal models of ALD.}, }
@article {pmid36156924, year = {2022}, author = {Soveral, LF and Korczaguin, GG and Schmidt, PS and Nunes, IS and Fernandes, C and Zárate-Bladés, CR}, title = {Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection.}, journal = {World journal of gastroenterology}, volume = {28}, number = {33}, pages = {4762-4772}, pmid = {36156924}, issn = {2219-2840}, mesh = {Bile Acids and Salts ; *Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; Fatty Acids, Volatile ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces/microbiology ; Humans ; Inflammation Mediators ; Neoplasm Recurrence, Local ; Recurrence ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT.}, }
@article {pmid36156162, year = {2022}, author = {Sabanov, A and Mehdorn, M and Gockel, I and Stelzner, S}, title = {[64/m-Fresh blood on the stool : Preparation for the medical specialist examination: part 20].}, journal = {Chirurgie (Heidelberg, Germany)}, volume = {93}, number = {Suppl 1}, pages = {88-94}, pmid = {36156162}, issn = {2731-698X}, mesh = {Feces ; *Medicine ; }, }
@article {pmid36155806, year = {2022}, author = {Benech, N and Koppe, L}, title = {Is there a place for faecal microbiota transplantation in chronic kidney disease?.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {37}, number = {12}, pages = {2303-2306}, doi = {10.1093/ndt/gfac277}, pmid = {36155806}, issn = {1460-2385}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Renal Insufficiency, Chronic/therapy ; }, }
@article {pmid36155217, year = {2022}, author = {Zhai, Y and Zhou, W and Yan, X and Qiao, Y and Guan, L and Zhang, Z and Liu, H and Jiang, J and Liu, J and Peng, L}, title = {Astragaloside IV ameliorates diet-induced hepatic steatosis in obese mice by inhibiting intestinal FXR via intestinal flora remodeling.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {107}, number = {}, pages = {154444}, doi = {10.1016/j.phymed.2022.154444}, pmid = {36155217}, issn = {1618-095X}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Ceramides/metabolism/pharmacology ; Diet, High-Fat/adverse effects ; Fibroblast Growth Factors/metabolism ; *Gastrointestinal Microbiome ; Glucagon-Like Peptide 1/metabolism ; Intestines ; Liver ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; RNA, Ribosomal, 16S ; Receptors, Cytoplasmic and Nuclear/metabolism ; *Saponins/metabolism/pharmacology ; Sterols/metabolism ; Triterpenes ; }, abstract = {BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major clinical and public health burden worldwide with no established pharmacological therapy. Changes in the intestinal flora and associated metabolite bile acids (BAs) have been described in NAFLD. Astragaloside IV (AS-IV) is a low drug permeability saponin with protective effects against multiple diseases. However, the specific mechanism underlying the involvement of AS-IV in the regulation of NAFLD is yet to be clarified.<br><br>PURPOSE: This study aimed to investigate the effect of AS-IV on NAFLD and explore whether intestinal flora was involved.<br><br>METHODS: The effect of AS-IV was evaluated on high-fat diet-fed mice. Real-time PCR, immunohistochemistry, immunofluorescence, and biochemical analyses were performed. 16S rRNA gene sequencing and UPLC-TQMS were used to determine the alterations in the intestinal flora and concentration of BAs. Fecal microbiota transplantation (FMT) and intestine-specific farnesoid X receptor (FXR) knockout were also performed.<br><br>RESULTS: AS-IV treatment alleviated diet-induced metabolic impairments, particularly hepatic steatosis. These changes occurred in the setting of decreased intestinal bile salt hydrolase (BSH)-expressing flora. Further analysis showed that the reduced BSH activity increased intestinal tauro-&#x3b2;-muricholic acid levels, an inhibitor of intestinal FXR. Inhibition of intestinal FXR signaling by AS-IV was accompanied by decreased expression of intestinal fibroblast growth factor 15 and subsequent hepatic FXR activation as well as increased glucagon-like peptide-1 and decreased ceramide production, all of which contribute to the inhibition of sterol regulatory element-binding protein-1c-mediated hepatic steatosis. Furthermore, intestine-specific Fxr knockout and FMT further demonstrated an FXR- and intestinal flora-dependent preventive effect of AS-IV on hepatic steatosis.<br><br>CONCLUSION: These results show that the changes in intestinal flora and BAs serve an essential role in the remission of hepatic steatosis by AS-IV, thereby suggesting that AS-IV may be used as a prebiotic agent to provide viable treatment for NAFLD.}, }
@article {pmid36154539, year = {2024}, author = {Zoghi, S and Abbasi, A and Heravi, FS and Somi, MH and Nikniaz, Z and Moaddab, SY and Ebrahimzadeh Leylabadlo, H}, title = {The gut microbiota and celiac disease: Pathophysiology, current perspective and new therapeutic approaches.}, journal = {Critical reviews in food science and nutrition}, volume = {64}, number = {8}, pages = {2176-2196}, doi = {10.1080/10408398.2022.2121262}, pmid = {36154539}, issn = {1549-7852}, mesh = {Humans ; *Celiac Disease/therapy/genetics ; *Gastrointestinal Microbiome ; Quality of Life ; Intestines ; Glutens ; *Probiotics/therapeutic use ; Dysbiosis ; }, abstract = {Celiac disease (CD) as a chronic gluten-sensitive intestinal condition, mainly affects genetically susceptible hosts. The primary determinants of CD have been identified as environmental and genetic variables. The development of CD is significantly influenced by environmental factors, including the gut microbiome. Therefore, gut microbiome re-programming-based therapies using probiotics, prebiotics, postbiotics, gluten-free diet, and fecal microbiota transplantation have shown promising results in the modification of the gut microbiome. Due to the importance and paucity of information regarding the CD pathophysiology, in this review, we have covered the association between CD development and gut microbiota, the effects of infectious agents, particularly the recent Covid-19 infection in CD patients, and the efficacy of potential therapeutic approaches in the CD have been discussed. Hence, scientific literature indicates that the diverse biological functions of the gut microbiota against immunomodulatory responses have made microbiome-based therapy an alternative therapeutic paradigm to ameliorate the symptoms of CD and quality of life. However, the exact potential of microbiota-based techniques that aims to quantitatively and qualitatively alter the gut microbiota to be used in the treatment and ameliorate the symptoms of CD will be determined with further research in the future.}, }
@article {pmid36153786, year = {2022}, author = {Najmi, M and Tran, T and Witt, RG and Nelson, KC}, title = {Modulation of the Gut Microbiome to Enhance Immunotherapy Response in Metastatic Melanoma Patients: A Clinical Review.}, journal = {Dermatology and therapy}, volume = {12}, number = {11}, pages = {2489-2497}, pmid = {36153786}, issn = {2193-8210}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; }, abstract = {For patients with metastatic melanoma, immunotherapy agents represent a promising treatment option, and researchers are actively seeking to identify factors that may predict a favorable response in patients. Recent studies have elucidated possible associations between the gut microbiome and the effects of immunotherapy, where variations in the gut microbiome may influence treatment response and frequency of adverse effects. In this clinical review, we describe the current literature related to the gut microbiome in the setting of immunotherapy, and we provide an overview of interventions under investigation that may modulate the gut microbiome. These interventions include fecal microbiota transplantation, probiotics, and dietary modifications.}, }
@article {pmid36152636, year = {2022}, author = {Baunwall, SMD and Andreasen, SE and Hansen, MM and Kelsen, J and Høyer, KL and Rågård, N and Eriksen, LL and Støy, S and Rubak, T and Damsgaard, EMS and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomised, double-blind, placebo-controlled trial.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {12}, pages = {1083-1091}, doi = {10.1016/S2468-1253(22)00276-X}, pmid = {36152636}, issn = {2468-1253}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; Vancomycin/therapeutic use ; *Clostridium Infections/therapy ; Diarrhea/therapy/drug therapy ; Double-Blind Method ; }, abstract = {BACKGROUND: Clostridioides difficile infection is an urgent antibiotic-associated health threat with few treatment options. Microbiota restoration with faecal microbiota transplantation is an effective treatment option for patients with multiple recurring episodes of C difficile. We compared the efficacy and safety of faecal microbiota transplantation compared with placebo after vancomycin for first or second C difficile infection.<br><br>METHODS: We did a randomised, double-blind, placebo-controlled trial (EarlyFMT) at a university hospital in Aarhus, Denmark. Eligible patients were aged 18 years or older with first or second C difficile infection (defined as &#x2265;3 watery stools [Bristol stool chart score 6-7] per day and a positive C difficile PCR test). Patients were randomly assigned (1:1) to faecal microbiota transplantation or placebo administered on day 1 and between day 3 and 7, after they had received 125 mg oral vancomycin four times daily for 10 days. Randomisation was done by investigators using a computer-generated randomisation list provided by independent staff. Patients and investigators were masked to the treatment group. The primary endpoint was resolution of C difficile-associated diarrhoea (CDAD) 8 weeks after treatment. We followed up patients for 8 weeks or until recurrence. We planned to enrol 84 patients with a prespecified interim analysis after 42 patients. The primary outcome and safety outcomes were analysed in the intention-to-treat population, which included all randomly assigned patients. The trial is registered with ClinicalTrials.gov, NCT04885946.<br><br>FINDINGS: Between June 21, 2021, and April 1, 2022, we consecutively screened 86 patients, of whom 42 were randomly assigned to faecal microbiota transplantation (n=21) or placebo (n=21). The trial was stopped after the interim analysis done on April 7, 2022 for ethical reasons because a significantly lower rate of resolution was identified in the placebo group compared with the faecal microbiota transplantation group (Haybittle-Peto boundary limit p<0&#xb7;001). 19 (90%; 95% CI 70-99) of 21 patients in the faecal microbiota transplantation group and seven (33%, 95% CI 15-57) of 21 patients in the placebo group had resolution of CDAD at week 8 (p=0&#xb7;0003). The absolute risk reduction was 57% (95% CI 33-81). Overall, 204 adverse events occurred, with one or more adverse events being reported in 20 of 21 patients in the faecal microbiota transplantation group and all 21 patients in the placebo group. Diarrhoea (n=23 in the faecal microbiota transplantation group; n=14 in the placebo group) and abdominal pain (n=14 in the faecal microbiota transplantation group; n=11 in the placebo group) were the most common adverse events. Three serious adverse events possibly related to study treatment occurred (n=1 in the faecal microbiota transplantation group; n=2 in the placebo group), but no deaths or colectomies during the 8-week follow-up.<br><br>INTERPRETATION: In patients with first or second C difficile infection, first-line faecal microbiota transplantation is highly effective and superior to the standard of care vancomycin alone in achieving sustained resolution from C difficile.<br><br>FUNDING: Innovation Fund Denmark.}, }
@article {pmid36152634, year = {2022}, author = {Allegretti, JR}, title = {Should faecal microbiota transplantation be used earlier in the treatment framework?.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {12}, pages = {1062-1063}, doi = {10.1016/S2468-1253(22)00301-6}, pmid = {36152634}, issn = {2468-1253}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Clostridioides difficile ; *Colitis, Ulcerative/therapy ; }, }
@article {pmid36151544, year = {2022}, author = {Wang, C and Wang, Y and Yang, H and Tian, Z and Zhu, M and Sha, X and Ran, J and Li, L}, title = {Uygur type 2 diabetes patient fecal microbiota transplantation disrupts blood glucose and bile acid levels by changing the ability of the intestinal flora to metabolize bile acids in C57BL/6 mice.}, journal = {BMC endocrine disorders}, volume = {22}, number = {1}, pages = {236}, pmid = {36151544}, issn = {1472-6823}, mesh = {Animals ; Bile Acids and Salts ; Blood Glucose/metabolism ; Chromatography, Liquid ; DNA, Ribosomal ; Deoxycholic Acid ; *Diabetes Mellitus, Type 2 ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Glucagon-Like Peptide 1 ; Humans ; Insulin ; Mice ; Mice, Inbred C57BL ; Receptors, Calcitriol ; Saline Solution ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: Our epidemiological study showed that the intestinal flora of Uygur T2DM patients differed from that of normal glucose-tolerant people. However, whether the Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and the mechanism behind has not been reported. This study was designed to explore whether Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and its mechanism.<br><br>METHODS: The normal diet and high fat diet group consisted of C57BL/6 mice orally administered 0.2&#x2009;mL sterile normal saline. For the MT (microbiota transplantation) intervention groups, C57BL/6 mice received oral 0.2&#x2009;mL faecal microorganisms from Uygur T2DM. All mice were treated daily for 8&#x2009;weeks and Blood glucose levels of mice were detected. Mice faecal DNA samples were sequenced and quantified using 16S rDNA gene sequencing. Then we detected the ability of the intestinal flora to metabolize bile acids (BAs) through co-culture of fecal bacteria and BAs. BA levels in plasma were determined by UPLC-MS. Further BA receptors and glucagon-like peptide-1 (GLP-1) expression levels were determined with RT-q PCR and western blotting.<br><br>RESULTS: MT impaired insulin and oral glucose tolerance. Deoxycholic acid increased and tauro-&#x3b2;-muricholic acid and the non-12-OH BA:12-OH BA ratio decreased in plasma. MT improved the ability of intestinal flora to produce deoxycholic acid. Besides, the vitamin D receptor in the liver and ileum and GLP-1 in the ileum decreased significantly.<br><br>CONCLUSIONS: Uygur T2DM fecal microbiota transplantation disrupts glucose metabolism by changing the ability of intestinal flora to metabolize BAs and the BAs/GLP-1 pathway.}, }
@article {pmid36150095, year = {2022}, author = {Zhang, Y and Zhang, L and Mao, L and Fan, J and Jiang, X and Li, N and Fan, Y and Jiang, Z and Qin, X and Qiu, F and Jiang, Y and Liu, G and Zhang, J and Chen, C and Zou, Z}, title = {Intestinal Microbiota-derived Propionic Acid Protects against Zinc Oxide Nanoparticle-induced Lung Injury.}, journal = {American journal of respiratory cell and molecular biology}, volume = {67}, number = {6}, pages = {680-694}, doi = {10.1165/rcmb.2021-0515OC}, pmid = {36150095}, issn = {1535-4989}, mesh = {Mice ; Humans ; Animals ; *Zinc Oxide/pharmacology ; *Gastrointestinal Microbiome ; Propionates/pharmacology ; *Nanoparticles ; *Acute Lung Injury/chemically induced/prevention &amp; control ; Acetates ; }, abstract = {With the rapid development of nanotechnology, the risks of accidental and/or occupational exposure to zinc oxide nanoparticles (ZnONPs) are increasing. Inhalation of ZnONPs induces metal fume fever in humans and acute lung injury (ALI) in animal models. Although the intestinal microbiota is considered an important modulator of various diseases, the role and mechanism of intestinal microbiota in the pathology of ZnONP-induced ALI are unclear. Herein, we established an intratracheal instillation of a ZnONP-induced ALI mouse model and found that the inhalation of ZnONPs caused ALI along with a perturbation of intestinal flora. Antibiotic cocktail treatment-mediated depletion of intestinal microbiota aggravated ZnONP-induced ALI, and in contrast, fecal microbiota transplantation-mediated restoration of intestinal microbiota exerted the opposite effects. A decrease in short-chain fatty acids, the intestinal microbiota-derived metabolites in the plasma-in particular, acetic acid and propionic acid-occurred after exposure to ZnONPs. It is important to note that supplementation with propionic acid, but not acetic acid, ameliorated ZnONP-induced ALI. We also showed that the source of inflammatory cytokines might partially be the infiltration of macrophages. Supplementation with propionic acid was found to act on macrophages through the receptor GPR43, because knockdown of GPR43 sharply reversed the protective effects of propionic acid during the ZnONP-induced inflammatory response and oxidative stress in both primary alveolar macrophages and RAW 264.7 macrophage cell lines. Altogether, a novel gut-lung axis mechanism is revealed in which intestinal microbiota and their derived metabolite propionic acid play protective roles against ZnONP-induced ALI and suggest that fecal microbiota transplantation and supplementation with propionic acid are potential remedy strategies.}, }
@article {pmid36149765, year = {2022}, author = {Ziegler, S and Bereswill, S and Heimesaat, MM}, title = {Modulation of the intestinal microbiota impacts the efficacy of immunotherapy in cancer patients - A recent literature survey.}, journal = {European journal of microbiology &amp; immunology}, volume = {12}, number = {3}, pages = {63-72}, pmid = {36149765}, issn = {2062-509X}, abstract = {In line with the current development of individualized cancer treatments, targeted and specialized therapeutic regimens such as immunotherapy gain importance and factors improving its efficacy come into the focus of actual research. Given the orchestrated interaction of the intestinal microbiota with host immunity the modulation of the human gut microbiota represents a therapy-enhancing factor. We therefore performed an actual literature survey on the role of the gut microbiota composition and the effects of its modification during immunotherapy of cancer patients. The included 23 studies published in the past 10 years revealed that both, distinct bacterial species and genera including Faecalibacterium prausnitzii and Bifidobacterium, respectively, enhanced distinct immunotherapy responses following PD-1/PD-L1 and CTLA-4 blockage, for instance, resulting in a better clinical outcome of cancer patients. Conversely, a high intestinal abundance of Bacteroidetes and Fusobacterium species correlated with a less efficient immunotherapy resulting in shorter progress-free survival outcomes. In conclusion, modifications of the gut microbiota by fecal microbiota transplantation or application of probiotic compounds represent potential adjunct options for immunotherapy in cancer patients which needs to be further addressed in future trials to provide individually tailored and safe adjuvant therapeutic measures in the combat of cancer.}, }
@article {pmid36148693, year = {2023}, author = {López Cardona, J and Senosiaín Lalastra, C and Mesonero Gismero, F and García de la Filia Molina, I and Escribano Cruz, S and Trigo Gallego, G and Albillos, A}, title = {Exocrine pancreatic insufficiency and graft-versus-host disease.}, journal = {Revista espanola de enfermedades digestivas}, volume = {115}, number = {4}, pages = {210-211}, doi = {10.17235/reed.2022.9143/2022}, pmid = {36148693}, issn = {1130-0108}, mesh = {Male ; Humans ; Middle Aged ; *Exocrine Pancreatic Insufficiency/etiology ; *Cytomegalovirus Infections ; T-Lymphocytes ; Diarrhea ; *Graft vs Host Disease/etiology ; }, abstract = {We present the case of a 59-year-old man with acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two years later, he consulted for diarrhea and steatorrhea of 2-3 months of evolution with significant weight loss. Stool cultures and study of parasites were negative. Thyroid and celiac profile, cytomegalovirus viremia and colonoscopy, were normal. Fecal calprotectin and fecal clearance of alpha-1-Antitrypsin were normal but with almost undetectable fecal elastase (<15 ug/g). Pancreatic magnetic resonance reveals a generalized atrophy of the pancreas without other parenchymal or ductal alterations. The patient had no risk factors for chronic pancreatitis and was diagnosed with exocrine pancreatic insufficiency (EPI) associated with chronic graft-versus-host disease (GVHD). GVHD is caused by an immune-mediated reaction by donor T cells recognizing foreign antigens from the recipient. GVHD occurs in 80% of patients after allo-HSCT. Diarrhea is one of the most frequent manifestations, most often due to intestinal damage, opportunistic infections or chemoradiation effects.}, }
@article {pmid36145102, year = {2022}, author = {Chang, C and Yuan, X and Zhang, X and Chen, X and Li, K}, title = {Gastrointestinal Microbiome and Multiple Health Outcomes: Umbrella Review.}, journal = {Nutrients}, volume = {14}, number = {18}, pages = {}, pmid = {36145102}, issn = {2072-6643}, support = {2021YFS0022//Science and Technology Department of Sichuan Province/ ; }, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics ; *Synbiotics ; }, abstract = {In recent years, there has been growing concern about the impact of the gastrointestinal microbiome on human health outcomes. To clarify the evidence for a link between the gastrointestinal microbiome and a variety of health outcomes in humans, we conducted an all-encompassing review of meta-analyses and systematic reviews that included 195 meta-analyses containing 950 unique health outcomes. The gastrointestinal microbiome is related to mortality, gastrointestinal disease, immune and metabolic outcomes, neurological and psychiatric outcomes, maternal and infant outcomes, and other outcomes. Existing interventions for intestinal microbiota (such as probiotics, fecal microbiota transplant, etc.) are generally safe and beneficial to a variety of human health outcomes, but the quality of evidence is not high, and more detailed and well-designed randomized controlled trials are necessary.}, }
@article {pmid36144471, year = {2022}, author = {Siddiqui, R and Mungroo, MR and Alharbi, AM and Alfahemi, H and Khan, NA}, title = {The Use of Gut Microbial Modulation Strategies as Interventional Strategies for Ageing.}, journal = {Microorganisms}, volume = {10}, number = {9}, pages = {}, pmid = {36144471}, issn = {2076-2607}, abstract = {Gut microbial composition codevelops with the host from birth and is influenced by several factors, including drug use, radiation, psychological stress, dietary changes and physical stress. Importantly, gut microbial dysbiosis has been clearly associated with several diseases, including cancer, rheumatoid arthritis and Clostridium difficile-associated diarrhoea, and is known to affect human health and performance. Herein, we discuss that a shift in the gut microbiota with age and reversal of age-related modulation of the gut microbiota could be a major contributor to the incidence of numerous age-related diseases or overall human performance. In addition, it is suggested that the gut microbiome of long-lived animals such as reptiles should be investigated for their unique properties and contribution to the potent defense system of these species could be extrapolated for the benefit of human health. A range of techniques can be used to modulate the gut microbiota to have higher abundance of "beneficial" microbes that have been linked with health and longevity.}, }
@article {pmid36144420, year = {2022}, author = {Mazzawi, T and Hausken, T and Refsnes, PF and Hatlebakk, JG and Lied, GA}, title = {The Effect of Anaerobically Cultivated Human Intestinal Microbiota Compared to Fecal Microbiota Transplantation on Gut Microbiota Profile and Symptoms of Irritable Bowel Syndrome, a Double-Blind Placebo-Controlled Study.}, journal = {Microorganisms}, volume = {10}, number = {9}, pages = {}, pmid = {36144420}, issn = {2076-2607}, support = {F-10463/4800001918//Western Norway Regional Health Authority/ ; }, abstract = {Fecal microbiota transplantation (FMT) from healthy donors has been shown to improve the symptoms of irritable bowel syndrome (IBS) and changes the profile of the gut microbiota for the recipients. Alternatively, anaerobically cultivated human intestinal microbiota (ACHIM) can be used to manipulate the gut microbiota. The aim of the current study was to compare the efficacy and safety of ACHIM suspension with donor-FMT and placebo (patient's own feces) to treat IBS. Out of the 62 originally included eligible patients with diarrhea-predominant IBS and their respective donors, only 43 patients completed the study by answering the questionnaires and delivering fecal samples before transplantation and after 1, 4, 12 and 24 weeks. The patients were randomized into three subgroups for receiving ACHIM suspension (n = 17), donor-FMT (n = 11), or placebo (n = 15), and were followed up for 24 weeks. Fecal samples were analyzed by sequencing 16S rRNA gene using the GA-map Dysbiosis Test (Genetic Analysis AS, Oslo, Norway). IBS symptom questionnaires improved in all three subgroups. Bacterial strain signals in IBS patients were more significant for Actinobacteria spp. and Bifidobacteria spp. after receiving donor-FMT compared to placebo and for Alistipes onderdonkii before and after treatment in the subgroups of ACHIM and donor-FMT vs. placebo. These signals change after treatment with ACHIM suspension and donor FMT towards those measured for healthy controls, but not after placebo. IBS symptom questionnaires improved in all three forms of transplantation. Some bacterial strain signals were significantly different between ACHIM and donor-FMT vs. placebo. However, the placebo subgroup failed to change the gut microbiota towards signals measured for healthy controls. The safety and efficacy of ACHIM and donor-FMT seems similar in the current study, but further larger studies are needed.}, }
@article {pmid36142642, year = {2022}, author = {Belvoncikova, P and Maronek, M and Gardlik, R}, title = {Gut Dysbiosis and Fecal Microbiota Transplantation in Autoimmune Diseases.}, journal = {International journal of molecular sciences}, volume = {23}, number = {18}, pages = {}, pmid = {36142642}, issn = {1422-0067}, support = {APVV-17-0505//Slovak Research and Development Agency/ ; APVV-21-0370//Slovak Research and Development Agency/ ; VEGA 1/0649/21//Ministry of Education, Science, Research and Sport of the Slovak Republic/ ; }, mesh = {Animals ; *Autoimmune Diseases/therapy ; Autoimmunity ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Gut microbiota dysbiosis has recently been reported in a number of clinical states, including neurological, psychiatric, cardiovascular, metabolic and autoimmune disorders. Yet, it is not completely understood how colonizing microorganisms are implicated in their pathophysiology and molecular pathways. There are a number of suggested mechanisms of how gut microbiota dysbiosis triggers or sustains extraintestinal diseases; however, none of these have been widely accepted as part of the disease pathogenesis. Recent studies have proposed that gut microbiota and its metabolites could play a pivotal role in the modulation of immune system responses and the development of autoimmunity in diseases such as rheumatoid arthritis, multiple sclerosis or type 1 diabetes. Fecal microbiota transplantation (FMT) is a valuable tool for uncovering the role of gut microbiota in the pathological processes. This review aims to summarize the current knowledge about gut microbiota dysbiosis and the potential of FMT in studying the pathogeneses and therapies of autoimmune diseases. Herein, we discuss the extraintestinal autoimmune pathologies with at least one published or ongoing FMT study in human or animal models.}, }
@article {pmid36142552, year = {2022}, author = {Santiso-Bellón, C and Gozalbo-Rovira, R and Buesa, J and Rubio-Del-Campo, A and Peña-Gil, N and Navarro-Lleó, N and Cárcamo-Calvo, R and Yebra, MJ and Monedero, V and Rodríguez-Díaz, J}, title = {Replication of Human Norovirus in Mice after Antibiotic-Mediated Intestinal Bacteria Depletion.}, journal = {International journal of molecular sciences}, volume = {23}, number = {18}, pages = {}, pmid = {36142552}, issn = {1422-0067}, support = {PID2020-115403RB C21//Spanish Ministry of Science and Innovation/ ; PID2020-115403RB C22//Spanish Ministry of Science and Innovation/ ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; *Caliciviridae Infections ; DNA, Ribosomal ; Feces/microbiology ; Humans ; Infant ; Interleukin-13 ; Interleukin-4 ; Mice ; *Norovirus/genetics ; Toll-Like Receptor 2 ; Tumor Necrosis Factor-alpha ; }, abstract = {Human noroviruses (HuNoVs) are the main cause of acute gastroenteritis causing more than 50,000 deaths per year. Recent evidence shows that the gut microbiota plays a key role in enteric virus infectivity. In this context, we tested whether microbiota depletion or microbiota replacement with that of human individuals susceptible to HuNoVs infection could favor viral replication in mice. Four groups of mice (n = 5) were used, including a control group and three groups that were treated with antibiotics to eliminate the autochthonous intestinal microbiota. Two of the antibiotic-treated groups received fecal microbiota transplantation from a pool of feces from infants (age 1-3 months) or an auto-transplantation with mouse feces that obtained prior antibiotic treatment. The inoculation of the different mouse groups with a HuNoVs strain (GII.4 Sydney [P16] genotype) showed that the virus replicated more efficiently in animals only treated with antibiotics but not subject to microbiota transplantation. Viral replication in animals receiving fecal microbiota from newborn infants was intermediate, whereas virus excretion in feces from auto-transplanted mice was as low as in the control mice. The analysis of the fecal microbiota by 16S rDNA NGS showed deep variations in the composition in the different mice groups. Furthermore, differences were observed in the gene expression of relevant immunological mediators, such as IL4, CXCL15, IL13, TNFα and TLR2, at the small intestine. Our results suggest that microbiota depletion eliminates bacteria that restrict HuNoVs infectivity and that the mechanism(s) could involve immune mediators.}, }
@article {pmid36141228, year = {2022}, author = {Yang, M and Liu, S and Zhang, C}, title = {The Related Metabolic Diseases and Treatments of Obesity.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {9}, pages = {}, pmid = {36141228}, issn = {2227-9032}, abstract = {Obesity is a chronic disease characterized by the abnormal or excessive accumulation of body fat, affecting more than 1 billion people worldwide. Obesity is commonly associated with other metabolic disorders, such as type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular diseases, chronic kidney disease, and cancers. Factors such as a sedentary lifestyle, overnutrition, socioeconomic status, and other environmental and genetic conditions can cause obesity. Many molecules and signaling pathways are involved in the pathogenesis of obesity, such as nuclear factor (NF)-κB, Toll-like receptors (TLRs), adhesion molecules, G protein-coupled receptors (GPCRs), programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), and sirtuin 1 (SIRT1). Commonly used strategies of obesity management and treatment include exercise and dietary change or restriction for the early stage of obesity, bariatric surgery for server obesity, and Food and Drug Administration (FDA)-approved medicines such as semaglutide and liraglutide that can be used as monotherapy or as a synergistic treatment. In addition, psychological management, especially for patients with obesity and distress, is a good option. Gut microbiota plays an important role in obesity and its comorbidities, and gut microbial reprogramming by fecal microbiota transplantation (FMT), probiotics, prebiotics, or synbiotics shows promising potential in obesity and metabolic syndrome. Many clinical trials are ongoing to evaluate the therapeutic effects of different treatments. Currently, prevention and early treatment of obesity are the best options to prevent its progression to many comorbidities.}, }
@article {pmid36140337, year = {2022}, author = {Štofilová, J and Kvaková, M and Kamlárová, A and Hijová, E and Bertková, I and Guľašová, Z}, title = {Probiotic-Based Intervention in the Treatment of Ulcerative Colitis: Conventional and New Approaches.}, journal = {Biomedicines}, volume = {10}, number = {9}, pages = {}, pmid = {36140337}, issn = {2227-9059}, support = {VEGA 1/0393/20//Scientific Grant Agency of the Ministry of Education of Slovak Republic and Academy of Sciences/ ; }, abstract = {Although there are number of available therapies for ulcerative colitis (UC), many patients are unresponsive to these treatments or experience secondary failure during treatment. Thus, the development of new therapies or alternative strategies with minimal side effects is inevitable. Strategies targeting dysbiosis of gut microbiota have been tested in the management of UC due to the unquestionable role of gut microbiota in the etiology of UC. Advanced molecular analyses of gut microbiomes revealed evident dysbiosis in UC patients, characterized by a reduced biodiversity of commensal microbiota. Administration of conventional probiotic strains is a commonly applied approach in the management of the disease to modify the gut microbiome, improve intestinal barrier integrity and function, and maintain a balanced immune response. However, conventional probiotics do not always provide the expected health benefits to a patient. Their benefits vary significantly, depending on the type and stage of the disease and the strain and dose of the probiotics administered. Their mechanism of action is also strain-dependent. Recently, new candidates for potential next-generation probiotics have been discovered. This could bring to light new approaches in the restoration of microbiome homeostasis and in UC treatment in a targeted manner. The aim of this paper is to provide an updated review on the current options of probiotic-based therapies, highlight the effective conventional probiotic strains, and outline the future possibilities of next-generation probiotic and postbiotic supplementation and fecal microbiota transplantation in the management of UC.}, }
@article {pmid36140180, year = {2022}, author = {Girlanda, R and Liggett, JR and Jayatilake, M and Kroemer, A and Guerra, JF and Hawksworth, JS and Radkani, P and Matsumoto, CS and Zasloff, M and Fishbein, TM}, title = {The Microbiome and Metabolomic Profile of the Transplanted Intestine with Long-Term Function.}, journal = {Biomedicines}, volume = {10}, number = {9}, pages = {}, pmid = {36140180}, issn = {2227-9059}, support = {829895453//ROCHE ORGAN TRANSPLANTATION RESEARCH FOUNDATION (ROTF)/ ; }, abstract = {We analyzed the fecal microbiome by deep sequencing of the 16S ribosomal genes and the metabolomic profiles of 43 intestinal transplant recipients to identify biomarkers of graft function. Stool samples were collected from 23 patients with stable graft function five years or longer after transplant, 15 stable recipients one-year post-transplant and four recipients with refractory rejection and graft loss within one-year post-transplant. Lactobacillus and Streptococcus species were predominant in patients with stable graft function both in the short and long term, with a microbiome profile consistent with the general population. Conversely, Enterococcus species were predominant in patients with refractory rejection as compared to the general population, indicating profound dysbiosis in the context of graft dysfunction. Metabolomic analysis demonstrated significant differences between the three groups, with several metabolites in rejecting recipients clustering as a distinct set. Our study suggests that the bacterial microbiome profile of stable intestinal transplants is similar to the general population, supporting further application of this non-invasive approach to identify biomarkers of intestinal graft function.}, }
@article {pmid36140013, year = {2022}, author = {Khanna, S and Sims, M and Louie, TJ and Fischer, M and LaPlante, K and Allegretti, J and Hasson, BR and Fonte, AT and McChalicher, C and Ege, DS and Bryant, JA and Straub, TJ and Ford, CB and Henn, MR and Wang, EEL and von Moltke, L and Wilcox, MH}, title = {SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Clostridioides difficile Infection (rCDI).}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {9}, pages = {}, pmid = {36140013}, issn = {2079-6382}, support = {NA//Seres Therapeutics (United States)/ ; }, abstract = {Clostridioides difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20−25% of patients with a primary infection experience a recurrence, and the risk of recurrence increases with subsequent episodes to greater than 40%. The leading risk factor for CDI is broad-spectrum antibiotics, which leads to a loss of microbial diversity and impaired colonization resistance. Current FDA-approved CDI treatment strategies target toxin or toxin-producing bacteria, but do not address microbiome disruption, which is key to the pathogenesis of recurrent CDI. Fecal microbiota transplantation (FMT) reduces the risk of recurrent CDI through the restoration of microbial diversity. However, FDA safety alerts describing hospitalizations and deaths related to pathogen transmission have raised safety concerns with the use of unregulated and unstandardized donor-derived products. SER-109 is an investigational oral microbiome therapeutic composed of purified spore-forming Firmicutes. SER-109 was superior to a placebo in reducing CDI recurrence at Week 8 (12% vs. 40%, respectively; p < 0.001) in adults with a history of recurrent CDI with a favorable observed safety profile. Here, we discuss the role of the microbiome in CDI pathogenesis and the clinical development of SER-109, including its rigorous manufacturing process, which mitigates the risk of pathogen transmission. Additionally, we discuss compositional and functional changes in the gastrointestinal microbiome in patients with recurrent CDI following treatment with SER-109 that are critical to a sustained clinical response.}, }
@article {pmid36139402, year = {2022}, author = {Campagnoli, LIM and Marchesi, N and Vairetti, M and Pascale, A and Ferrigno, A and Barbieri, A}, title = {Age-Related NAFLD: The Use of Probiotics as a Supportive Therapeutic Intervention.}, journal = {Cells}, volume = {11}, number = {18}, pages = {}, pmid = {36139402}, issn = {2073-4409}, mesh = {Aged ; Ecosystem ; Humans ; Lipids ; *Non-alcoholic Fatty Liver Disease/metabolism ; *Probiotics/therapeutic use ; Reactive Oxygen Species ; }, abstract = {Human aging, a natural process characterized by structural and physiological changes, leads to alterations of homeostatic mechanisms, decline of biological functions, and subsequently, the organism becomes vulnerable to external stress or damage. In fact, the elderly population is prone to develop diseases due to deterioration of physiological and biological systems. With aging, the production of reactive oxygen species (ROS) increases, and this causes lipid, protein, and DNA damage, leading to cellular dysfunction and altered cellular processes. Indeed, oxidative stress plays a key role in the pathogenesis of several chronic disorders, including hepatic diseases, such as non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common liver disorder in the Western world, is characterized by intrahepatic lipid accumulation; is highly prevalent in the aging population; and is closely associated with obesity, insulin resistance, hypertension, and dyslipidemia. Among the risk factors involved in the pathogenesis of NAFLD, the dysbiotic gut microbiota plays an essential role, leading to low-grade chronic inflammation, oxidative stress, and production of various toxic metabolites. The intestinal microbiota is a dynamic ecosystem of microbes involved in the maintenance of physiological homeostasis; the alteration of its composition and function, during aging, is implicated in different liver diseases. Therefore, gut microbiota restoration might be a complementary approach for treating NAFLD. The administration of probiotics, which can relieve oxidative stress and elicit several anti-aging properties, could be a strategy to modify the composition and restore a healthy gut microbiota. Indeed, probiotics could represent a valid supplement to prevent and/or help treating some diseases, such as NAFLD, thus improving the already available pharmacological intervention. Moreover, in aging, intervention of prebiotics and fecal microbiota transplantation, as well as probiotics, will provide novel therapeutic approaches. However, the relevant research is limited, and several scientific research works need to be done in the near future to confirm their efficacy.}, }
@article {pmid36136718, year = {2022}, author = {Innocente, G and Patuzzi, I and Furlanello, T and Di Camillo, B and Bargelloni, L and Giron, MC and Facchin, S and Savarino, E and Azzolin, M and Simionati, B}, title = {Machine Learning and Canine Chronic Enteropathies: A New Approach to Investigate FMT Effects.}, journal = {Veterinary sciences}, volume = {9}, number = {9}, pages = {}, pmid = {36136718}, issn = {2306-7381}, support = {10232721//Regione del Veneto/ ; }, abstract = {Fecal microbiota transplantation (FMT) represents a very promising approach to decreasing disease activity in canine chronic enteropathies (CE). However, the relationship between remission mechanisms and microbiome changes has not been elucidated yet. The main objective of this study was to report the clinical effects of oral freeze-dried FMT in CE dogs, comparing the fecal microbiomes of three groups: pre-FMT CE-affected dogs, post-FMT dogs, and healthy dogs. Diversity analysis, differential abundance analysis, and machine learning algorithms were applied to investigate the differences in microbiome composition between healthy and pre-FMT samples, while Canine Chronic Enteropathy Clinical Activity Index (CCECAI) changes and microbial diversity metrics were used to evaluate FMT effects. In the healthy/pre-FMT comparison, significant differences were noted in alpha and beta diversity and a list of differentially abundant taxa was identified, while machine learning algorithms predicted sample categories with 0.97 (random forest) and 0.87 (sPLS-DA) accuracy. Clinical signs of improvement were observed in 74% (20/27) of CE-affected dogs, together with a statistically significant decrease in CCECAI (median value from 5 to 2 median). Alpha and beta diversity variations between pre- and post-FMT were observed for each receiver, with a high heterogeneity in the response. This highlighted the necessity for further research on a larger dataset that could identify different healing patterns of microbiome changes.}, }
@article {pmid36136534, year = {2022}, author = {Liu, A and Gao, W and Zhu, Y and Hou, X and Chu, H}, title = {Gut Non-Bacterial Microbiota: Emerging Link to Irritable Bowel Syndrome.}, journal = {Toxins}, volume = {14}, number = {9}, pages = {}, pmid = {36136534}, issn = {2072-6651}, mesh = {Dysbiosis ; *Fungicides, Industrial ; *Gastrointestinal Microbiome/physiology ; Humans ; *Irritable Bowel Syndrome/diagnosis/drug therapy ; *Microbiota ; }, abstract = {As a common functional gastrointestinal disorder, irritable bowel syndrome (IBS) significantly affects personal health and imposes a substantial economic burden on society, but the current understanding of its occurrence and treatment is still inadequate. Emerging evidence suggests that IBS is associated with gut microbial dysbiosis, but most studies focus on the bacteria and neglect other communities of the microbiota, including fungi, viruses, archaea, and other parasitic microorganisms. This review summarizes the latest findings that link the nonbacterial microbiota with IBS. IBS patients show less fungal and viral diversity but some alterations in mycobiome, virome, and archaeome, such as an increased abundance of Candida albicans. Moreover, fungi and methanogens can aid in diagnosis. Fungi are related to distinct IBS symptoms and induce immune responses, intestinal barrier disruption, and visceral hypersensitivity via specific receptors, cells, and metabolites. Novel therapeutic methods for IBS include fungicides, inhibitors targeting fungal pathogenic pathways, probiotic fungi, prebiotics, and fecal microbiota transplantation. Additionally, viruses, methanogens, and parasitic microorganisms are also involved in the pathophysiology and treatment. Therefore, the gut nonbacterial microbiota is involved in the pathogenesis of IBS, which provides a novel perspective on the noninvasive diagnosis and precise treatment of this disease.}, }
@article {pmid36135360, year = {2022}, author = {Gomez-Simmonds, A and Annavajhala, MK and Nunez, MP and Macesic, N and Park, H and Uhlemann, AC}, title = {Intestinal Dysbiosis and Risk of Posttransplant Clostridioides difficile Infection in a Longitudinal Cohort of Liver Transplant Recipients.}, journal = {mSphere}, volume = {7}, number = {5}, pages = {e0036122}, pmid = {36135360}, issn = {2379-5042}, support = {P30 DK132710/DK/NIDDK NIH HHS/United States ; R01 AI116939/AI/NIAID NIH HHS/United States ; TL1 TR001875/TR/NCATS NIH HHS/United States ; K23 AI137316/AI/NIAID NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Clostridioides difficile/genetics ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/complications ; *Liver Transplantation/adverse effects ; *Clostridium Infections/microbiology ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Clostridioides difficile infection (CDI) has a higher incidence in solid organ transplant recipients than other hospitalized patients and can lead to poor outcomes. Perturbations to the intestinal microbiome are common in patients undergoing liver transplant (LT); however, the impacts of microbial diversity and composition on risk of CDI in this patient population is incompletely understood. Here, we assessed patients in an established, longitudinal LT cohort for development of CDI within 1 year of transplant. Clinical data were compared for patients with and without CDI using univariable models. 16S rRNA sequencing of fecal samples was performed at multiple pre- and posttransplant time points to compare microbiome α- and β-diversity and enrichment of specific taxa in patients with and without CDI. Of 197 patients who underwent LT, 18 (9.1%) developed CDI within 1 year. Pre-LT Child-Pugh class C liver disease, postoperative biliary leak, and use of broad-spectrum antibiotics were significantly associated with CDI. Patients who developed CDI had significantly lower α-diversity than patients without CDI overall and in samples collected at months 1, 3, and 6. Microbial composition (β-diversity) differed between patients with and without CDI and across sampling time points, particularly later in their posttransplant course. We also identified 15 (8%) patients with toxigenic C. difficile colonization who did not develop CDI and may have had additional protective factors. In summary, clinical and microbiome factors are likely to converge to impart CDI risk. Along with enhanced preventive measures, there may be a role for microbiome modulation to restore microbial diversity in high-risk LT patients. IMPORTANCE Liver transplant (LT) recipients have high rates of Clostridioides difficile infection (CDI), which has been associated with poor outcomes, including graft-related complications and mortality, in prior studies. Susceptibility to CDI is known to increase following perturbations in intestinal commensal bacteria that enable germination of C. difficile spores and bacterial overgrowth. In LT patients, changes in the intestinal microbiome resulting from advanced liver disease, surgery, and other clinical factors is common and most pronounced during the early posttransplant period. However, the relationship between microbiome changes and CDI risk after LT remains unclear. In this study, we investigated clinical and microbiome factors associated with development of CDI within the first year after LT. The importance of this work is to identify patients with high-risk features that should receive enhanced preventive measures and may benefit from the study of novel strategies to reconstitute the intestinal microbiome after LT.}, }
@article {pmid36131643, year = {2023}, author = {Mörkl, S and Butler, MI and Lackner, S}, title = {Advances in the gut microbiome and mood disorders.}, journal = {Current opinion in psychiatry}, volume = {36}, number = {1}, pages = {1-7}, doi = {10.1097/YCO.0000000000000829}, pmid = {36131643}, issn = {1473-6578}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Mood Disorders/therapy ; *Depressive Disorder, Major/therapy ; *Probiotics/therapeutic use ; *Bipolar Disorder/therapy ; }, abstract = {PURPOSE OF REVIEW: The gut microbiome is in constant bidirectional communication with the brain through the microbiota-gut-brain-axis. Mood disorders are among the most common psychiatric disorders and include major depressive disorder and bipolar disorder. The gut microbiome is altered in individuals with mood disorders and has a role in its inflammatory pathophysiology. In this article, we performed a narrative review of clinical studies, randomized controlled trials and meta-analyses addressing advances in gut microbiome research in mood disorders and included articles that were published between 2021 and 2022.<br><br>RECENT FINDINGS: Studies highlight transdiagnostic alterations of microbiota in mood disorders, with reductions of butyrate-producing bacteria. Participants with major depressive disorder showed altered beta-diversity, while participants with bipolar disorder showed reduced alpha-diversity. Both disorders exhibit alterations in the metabolome. Early pilot studies addressed the possibility of using the gut microbiome for the prediction of treatment response and the blood microbiome for the diagnosis of psychiatric disorders. Findings from clinical trials support the use of probiotics as an add-on therapy for major depressive disorder. The second published case report in the literature reported a favourable outcome of a patient with bipolar disorder after faecal microbiota transplantation.<br><br>SUMMARY: Gut microbiome modulations allow new treatment strategies including the use of psychobiotics for the treatment and prevention of mood disorders. Well designed clinical trials aiming for personalized medicine are needed to investigate the efficacy and safety of psychobiotic interventions.}, }
@article {pmid36128620, year = {2022}, author = {Li, Y and Sun, H and Huang, Y and Yin, A and Zhang, L and Han, J and Lyu, Y and Xu, X and Zhai, Y and Sun, H and Wang, P and Zhao, J and Sun, S and Dong, H and Zhu, F and Wang, Q and Augusto Rohde, L and Xie, X and Sun, X and Xiong, L}, title = {Gut metagenomic characteristics of ADHD reveal low Bacteroides ovatus-associated host cognitive impairment.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2125747}, pmid = {36128620}, issn = {1949-0984}, mesh = {Animals ; *Attention Deficit Disorder with Hyperactivity/microbiology ; Bacteroides ; Cognition ; *Cognitive Dysfunction ; *Gastrointestinal Microbiome/physiology ; Humans ; Rats ; }, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous psychiatric disorder that can have three phenotypical presentations: inattentive (I-ADHD), hyperactive-impulsive (HI-ADHD), and combined (C-ADHD). Environmental factors correlated with the gut microbiota community have been implicated in the development of ADHD. However, whether different ADHD symptomatic presentations are associated with distinct microbiota compositions and whether patients could benefit from the correction of aberrant bacterial colonization are still largely unclear. We carried out metagenomic shotgun analysis with 207 human fecal samples to characterize the gut microbial profiles of patients with ADHD grouped according to their phenotypical presentation. Then, we transplanted the candidate low-abundance bacteria identified in patient subgroups into ADHD rats and evaluated ADHD-associated behaviors and neuronal activation in these rats. Patients with C-ADHD had a different gut microbial composition from that of healthy controls (HCs) (p = .02), but not from that of I-ADHD patients. Eight species became progressively attenuated or enriched when comparing the compositions of HCs to those of I-ADHD and C-ADHD; in particular, the abundance of Bacteroides ovatus was depleted in patients with C-ADHD. In turn, Bacteroides ovatus supplementation ameliorated spatial working memory deficits and reversed θ electroencephalogram rhythm alterations in ADHD rats. In addition, Bacteroides ovatus induced enhanced neuronal activation in the hippocampal CA1 subregion. These findings indicate that gut microbial characteristics that are unique to patients with C-ADHD may be masked when considering a more heterogeneous group of patients. We link the gut microbiota to brain function in an ADHD animal model, suggesting the relevance of testing a potential bacteria-based intervention for some aspects of ADHD.}, }
@article {pmid36126907, year = {2023}, author = {Vaughn, BP and Fischer, M and Kelly, CR and Allegretti, JR and Graiziger, C and Thomas, J and McClure, E and Kabage, AJ and Khoruts, A}, title = {Effectiveness and Safety of Colonic and Capsule Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {21}, number = {5}, pages = {1330-1337.e2}, doi = {10.1016/j.cgh.2022.09.008}, pmid = {36126907}, issn = {1542-7714}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces ; Treatment Outcome ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Recurrence ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) emerged as rescue treatment for multiply recurrent Clostridioides difficile infections (rCDIs) nonresponsive to standard therapy. However, estimation of FMT efficacy varies among different protocols and formulations, while placebo-controlled clinical trials have excluded most rCDI patients because of medical comorbidities. This study aimed to determine the safety and effectiveness of capsule FMT (cap-FMT) and colonoscopy FMT (colo-FMT) for rCDI using standardized products in a large, multicenter, prospective, real-world cohort.<br><br>METHODS: Clinical outcomes and adverse events after FMT performed for rCDI at 6 sites were captured in a prospective registry. FMT was performed using 1 of 2 standardized formulations of microbiota manufactured by the University of Minnesota Microbiota Therapeutics Program, freeze-dried/encapsulated or frozen-thawed/liquid. The FMT administration route was determined by the treating physician. The rCDI cure rate was assessed at 1 and 2 months. Safety data were collected within the first 72 hours and at 1 and 2 months. Logistic regression was used to investigate factors associated with FMT failure.<br><br>RESULTS: A total of 301 FMTs were performed in 269 unique patients. Two-thirds were cap-FMT. CDI cure rates were 86% (95% CI, 82%-90%) at 1 month and 81% (95% CI, 75%-86%) at 2 months. There was no difference in the 1-month or 2-month cure rate between cap-FMT and colo-FMT. Cap-FMT recipients were older and less likely to be immunosuppressed or have inflammatory bowel disease. Patient factors of older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression. In addition, post-FMT antibiotic use was associated with FMT failure at 2 months. One serious adverse event was related to colonoscopy (aspiration pneumonia), otherwise no new safety signals were identified.<br><br>CONCLUSIONS: Cap-FMT using freeze-dried capsules has a similar safety and effectiveness profile compared with colo-FMT, without the procedural risks of colonoscopy. Although highly effective overall, patient selection is a key factor to optimizing FMT success.}, }
@article {pmid36126902, year = {2022}, author = {Cooper, TE and Scholes-Robertson, N and Craig, JC and Hawley, CM and Howell, M and Johnson, DW and Teixeira-Pinto, A and Jaure, A and Wong, G}, title = {Synbiotics, prebiotics and probiotics for solid organ transplant recipients.}, journal = {The Cochrane database of systematic reviews}, volume = {9}, number = {9}, pages = {CD014804}, pmid = {36126902}, issn = {1469-493X}, mesh = {Adult ; Albumins ; Anti-Bacterial Agents/therapeutic use ; *Cardiovascular Diseases ; Dysbiosis ; Endotoxins ; Humans ; Lipids ; *Organ Transplantation ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {BACKGROUND: Solid organ transplantation has seen improvements in both surgical techniques and immunosuppression, achieving prolonged survival. Essential to graft acceptance and post-transplant recovery, immunosuppressive medications are often accompanied by a high prevalence of gastrointestinal (GI) symptoms and side effects. Apart from GI side effects, long-term exposure to immunosuppressive medications has seen an increase in drug-related morbidities such as diabetes mellitus, hyperlipidaemia, hypertension, and malignancy. Non-adherence to immunosuppression can lead to an increased risk of graft failure. Recent research has indicated that any microbial imbalances (otherwise known as gut dysbiosis or leaky gut) may be associated with cardiometabolic diseases in the long term. Current evidence suggests a link between the gut microbiome and the production of putative uraemic toxins, increased gut permeability, and transmural movement of bacteria and endotoxins and inflammation. Early observational and intervention studies have been investigating food-intake patterns, various synbiotic interventions (antibiotics, prebiotics, or probiotics), and faecal transplants to measure their effects on microbiota in treating cardiometabolic diseases. It is believed high doses of synbiotics, prebiotics and probiotics are able to modify and improve dysbiosis of gut micro-organisms by altering the population of the micro-organisms. With the right balance in the gut flora, a primary benefit is believed to be the suppression of pathogens through immunostimulation and gut barrier enhancement (less permeability of the gut).<br><br>OBJECTIVES: To assess the benefits and harms of synbiotics, prebiotics, and probiotics for recipients of solid organ transplantation.<br><br>SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 9 March 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.<br><br>SELECTION CRITERIA: We included randomised controlled trials measuring and reporting the effects of synbiotics, prebiotics, or probiotics, in any combination and any formulation given to solid organ transplant recipients (any age and setting). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.<br><br>DATA COLLECTION AND ANALYSIS: Data extraction was independently carried out by two authors using a standard data extraction form. The methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.<br><br>MAIN RESULTS: Five studies (250 participants) were included in this review. Study participants were adults with a kidney (one study) or liver (four studies) transplant. One study compared a synbiotic to placebo, two studies compared a probiotic to placebo, and two studies compared a synbiotic to a prebiotic. Overall, the quality of the evidence is poor. Most studies were judged to have unclear (or high) risk of bias across most domains. Of the available evidence, meta-analyses undertaken were of limited data from small studies. Across all comparisons, GRADE evaluations for all outcomes were judged to be very low certainty evidence. Very low certainty evidence implies that we are very uncertain about results (not estimable due to lack of data or poor quality). Synbiotics had uncertain effects on the change in microbiota composition (total plasma p-cresol), faecal characteristics, adverse events, kidney function or albumin concentration (1 study, 34 participants) compared to placebo. Probiotics had uncertain effects on GI side effects, infection rates immediately post-transplant, liver function, blood pressure, change in fatty liver, and lipids (1 study, 30 participants) compared to placebo. Synbiotics had uncertain effects on graft health (acute liver rejection) (2 studies, 129 participants: RR 0.73, 95% CI 0.43 to 1.25; 2 studies, 129 participants; I&#xb2; = 0%), the use of immunosuppression, infection (2 studies, 129 participants: RR 0.18, 95% CI 0.03 to 1.17; I&#xb2; = 66%), GI function (time to first bowel movement), adverse events (2 studies, 129 participants: RR 0.79, 95% CI 0.40 to 1.59; I&#xb2; = 20%), serious adverse events (2 studies, 129 participants: RR 1.49, 95% CI 0.42 to 5.36; I&#xb2; = 81%), death (2 studies, 129 participants), and organ function measures (2 studies; 129 participants) compared to prebiotics.<br><br>AUTHORS' CONCLUSIONS: This review highlights the severe lack of high-quality RCTs testing the efficacy of synbiotics, prebiotics or probiotics in solid organ transplant recipients. We have identified significant gaps in the evidence. Despite GI symptoms and postoperative infection being the most common reasons for high antibiotic use in this patient population, along with increased morbidity and the growing antimicrobial resistance, we found very few studies that adequately tested these as alternative treatments. There is currently no evidence to support or refute the use of synbiotics, prebiotics, or probiotics in solid organ transplant recipients, and findings should be viewed with caution. We have identified an area of significant uncertainty about the efficacy of synbiotics, prebiotics, or probiotics in solid organ transplant recipients. Future research in this field requires adequately powered RCTs comparing synbiotics, prebiotics, and probiotics separately and with placebo measuring a standard set of core transplant outcomes. Six studies are currently ongoing (822 proposed participants); therefore, it is possible that findings may change with their inclusion in future updates.}, }
@article {pmid36126873, year = {2022}, author = {Zhang, Q and Li, T and Niu, J and Xiao, J and Zhang, M and Zhang, R and Chen, D and Shi, Y and Zhang, X and Hu, X and Yu, B and Feng, J and Fang, Q}, title = {Inhibitory effects of antibiotic-induced gut microbiota depletion on acute itch behavior in mice.}, journal = {Brain research bulletin}, volume = {190}, number = {}, pages = {50-61}, doi = {10.1016/j.brainresbull.2022.09.014}, pmid = {36126873}, issn = {1873-2747}, mesh = {Animals ; Mice ; Male ; *Gastrointestinal Microbiome/physiology ; Mice, Inbred C57BL ; Anti-Bacterial Agents/pharmacology ; Pruritus/chemically induced/drug therapy ; Serotonin/pharmacology ; }, abstract = {BACKGROUND: The gut microbiota is known to be associated with the regulation of many neurological diseases and behaviors, including chronic pain. However, it is unclear whether the gut microbiota is critical to the itch sensation. In this study, we investigated the effects of gut microbiota depletion on acute itch.<br><br>METHODS: First, an antibiotic cocktail was orally administered to deplete the gut microbiota in male C57BL/6 mice. Then, pruritogens were intradermally injected to induce acute itch behavior. In addition, antibiotic-treated mice received transplantation of fecal microbiota from untreated mice, followed by tests for acute itch. The changes in c-Fos expression in trigeminal ganglia (TG) neurons were also investigated by immunofluorescence staining.<br><br>RESULTS: Our results indicated that chronic antibiotic treatment significantly reduced the diversity and richness of the gut microbiota of mice. Compared to vehicle-treated mice, antibiotic-treated mice showed reductions in acute itch behavior induced by compound 48/80, chloroquine (CQ), and serotonin (5-HT), respectively. Moreover, repositioning of microbiota reversed the reductions in acute itch behavior in antibiotic-treated mice. In addition, immunofluorescence staining revealed that antibiotic-treated mice displayed decreased c-Fos expression in ipsilateral TG compared to controls.<br><br>CONCLUSIONS: Our study, for the first time, discovered that antibiotic-induced gut microbiota depletion could reduce acute itch behavior, which may be connected with decreased TG neuronal activity.}, }
@article {pmid36125532, year = {2023}, author = {Xia, Y and Tian, Y and Zhou, D and Zhang, L and Cai, Y and Fu, S and Zhang, X and Gao, Y and Chen, Q and Gao, P}, title = {Gut microbiota involved in spermatogenic function of Sancai Lianmei granules in obese mice.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {396}, number = {1}, pages = {83-97}, pmid = {36125532}, issn = {1432-1912}, support = {2022YFS0411//Science and Technology Plan Project of Sichuan Province (Key Research and Development Project)/ ; 2100601//2022 national famous and old Chinese medicine expert Zhang Shuwu inheritance studio construction project/ ; 2021MS023//Sichuan Provincial Administration of Traditional Chinese Medicine Scientific Research Project/ ; 2019-YF05- 00064-SN//Chengdu Science and Technology Bureau Technological Innovation R&amp;D Project/ ; }, mesh = {Male ; Animals ; Mice ; *Gastrointestinal Microbiome ; Mice, Obese ; Semen Analysis ; Semen/metabolism ; Sperm Motility ; Obesity/therapy/metabolism ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; }, abstract = {Obesity is a well-established cause of reduced fertility and semen quality in men. Current evidence suggests that Sancai Lianmei granules (SCLM) effectively improve sexual function and semen quality in diabetic patients, while the gut microbiota can influence disease metabolism through various mechanisms. However, the effect of SCLM on the obesity-induced decrease in semen quality and on the gut microbiota is unclear. This study aimed to investigate the effects of SCLM on spermatogenic function and gut microbiota in obese mice. Obese mice were induced by a high-fat diet, and lipid metabolism, spermatogenic function, inflammatory factors, oxidative stress, and autophagy were analyzed to determine the effects of SCLM and SCLM-fecal microbiota transplantation (FMT). In addition, changes in the gut microbiota of mice were analyzed. SCLM and SCLM + FMT could effectively reduce the levels of total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); decrease the expression of oxidative stress products malondialdehyde (MDA) and 8-hydroxyde-oxyguanosine (8-OHdG); and increase sperm density and sperm viability in obese mice while inhibiting the inflammatory responses and excessive cellular autophagy, indicating that SCLM and SCLM + FMT exerted a protective effect on spermatogenic functions. Furthermore, SCLM affected the gut microbiota composition in mice. This study determined that obesity can lead to reduced sperm motility and affect the composition of the gut microbiota, while SCLM can regulate blood lipids in mice directly or indirectly by regulating gut microbiota changes, and may improve sperm motility in obese mice by reducing oxidative stress and autophagy. In addition, FMT enhanced this effect, which may be related to the diversity of gut microbiota.}, }
@article {pmid36123355, year = {2022}, author = {Noguès, EB and Kropp, C and Bétemps, L and de Sousa, C and Chain, F and Auger, S and Azevedo, V and Langella, P and Chatel, JM}, title = {Lactococcus lactis engineered to deliver hCAP18 cDNA alleviates DNBS-induced colitis in C57BL/6 mice by promoting IL17A and IL10 cytokine expression.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {15641}, pmid = {36123355}, issn = {2045-2322}, mesh = {Animals ; Cathelicidins/*metabolism ; *Colitis/chemically induced/genetics/therapy ; Cytokines/metabolism ; DNA, Complementary/metabolism ; Dinitrofluorobenzene/analogs &amp; derivatives ; Interleukin-10/genetics/metabolism ; Interleukin-17/metabolism ; *Lactococcus lactis/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; }, abstract = {With its antimicrobial and immunomodulating properties, the cathelicidin (LL37) plays an important role in innate immune system. Here, we attempted to alleviate chemically induced colitis using a lactococci strain that either directly expressed the precursor to LL37, hCAP18 (LL-pSEC:hCAP18), or delivered hCAP18 cDNA to host cells under the control of the cytomegalovirus promoter (LL-Probi-H1:hCAP18). We also investigated whether the alleviation of symptoms could be explained through modification of the gut microbiota by hCAP18. Mice were administered daily doses of LL-pSEC:hCAP18 or LL-Probi-H1:hCAP18. On day 7, colitis was induced by DNBS. During autopsy, we assessed macroscopic tissue damage in the colon and collected tissue samples for the characterization of inflammation markers and histological analysis. Feces were collected at day 7 for 16S DNA sequencing. We also performed a fecal transplant experiment in which mice underwent colon washing and received feces from Lactococcus lactis-treated mice before DNBS-colitis induction. Treatment with LL-Probi-H1:hCAP18 reduced the severity of colitis symptoms. The protective effects were accompanied by increased levels of IL17A and IL10 in mesenteric lymph node cells. L. lactis administration altered the abundance of Lachnospiraceae and Muribaculaceae. However, fecal transplant from L. lactis-treated mice did not improve DNBS-induced symptoms in recipient mice.}, }
@article {pmid36121613, year = {2022}, author = {Singh, A and Mahajan, R and Kahlon, BK and Dhaliwal, AS and Midha, V and Mehta, V and Bansal, N and Singh, D and Sood, A}, title = {Early fecal microbiome transfer after donor defecation determines response in patients with moderate to severe ulcerative colitis.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {41}, number = {4}, pages = {389-396}, pmid = {36121613}, issn = {0975-0711}, mesh = {Adult ; *Colitis, Ulcerative/etiology/therapy ; Defecation ; Fecal Microbiota Transplantation/methods ; Feces ; Humans ; Male ; *Microbiota ; Middle Aged ; Remission Induction ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiome transfer (FMT) targeting gut microbiome dysbiosis is an emerging therapy for ulcerative colitis (UC). There is however no consensus on protocols for performing FMT in UC, especially in relation to time after donor feces defecation.<br><br>METHODS: This is a single-center retrospective analysis of patients with moderate-severe UC (total Mayo Clinic score &#x2265;6 and endoscopic Mayo Clinic subscore of &#x2265;2) treated with FMT between September 2017 and December 2019 at Dayanand Medical College and Hospital, Ludhiana,&#xa0;India. Fresh fecal samples from unrelated healthy voluntary donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. Time interval between donor feces defecation and FMT procedure was recorded for each FMT session and the mean time of seven sessions was designated aika. Impact of aika on clinical response and safety of FMT was evaluated.<br><br>RESULTS: During the study period, 123 adult patients (mean age 33.75&#xb1;11.97 years, 61.8% [n=76] males) with moderate-severe UC (mean total Mayo Clinic and endoscopic Mayo Clinic scores 7.49&#xb1;1.60 and 2.50&#xb1;0.50, respectively) were treated with FMT. The mean aika was 2.29&#xb1;0.75 h. The aika was smaller in patients who responded to FMT as compared to non-responders (2.13&#xb1;0.75&#xa0;h vs. 2.71&#xb1;0.76 h, p=0.0002) as well as in patients achieving clinical remission (2.15&#xb1;0.76 h vs. 2.42&#xb1;0.76 h, p=0.05). There was no significant impact of aika on adverse effects except for&#xa0;the incidence of borborygmi after FMT, which was higher in patients with aika &#x2264;2 h.<br><br>CONCLUSION: Early FMT after donor feces defecation favorably impacts the clinical response rates in patients with active UC.}, }
@article {pmid36117374, year = {2022}, author = {Ye, C and Chen, QY and Yan, YM and Lv, XQ and Ma, CL and Li, N and Qin, HL}, title = {[Establishment and preliminary clinical application of human intestinal fluid transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {819-825}, doi = {10.3760/cma.j.cn441530-20220601-00239}, pmid = {36117374}, issn = {1671-0274}, support = {SHDC2020CR1030B, SHDC2020CR4026//Clinical Research Plan of SHDC/ ; 21Y11908300//Shanghai Action Plan on Science, Technology and Innovation/ ; }, mesh = {Bacteria ; Child ; Fecal Microbiota Transplantation/methods ; *Glycerol ; Humans ; Powders ; *Trypan Blue ; }, abstract = {Objective: To explore and establish the preparation system of human intestinal fluid transplantation (HIFT) and HIFT capsule, and to preliminarily apply it to clinic. Methods: Strict standards for donor screening and management were established. The nasojejunal tube was catheterized into the distal jejunum, and then it was connected with an improved disposable sterile negative pressure collection device for the collection of human intestinal fluid. After that, it was prepared into capsules by filtering, adding 10% glycerin protectant and freeze-drying method. The amount of living bacteria was used as the standard of therapeutic dose. The living bacteria amount in fluid is ≥ 5.0×10[8] /mL and the living bacteria proportion is ≥ 83%; the living bacteria amount in powder is ≥ 2.0×10[6] /g and the living bacteria proportion is ≥ 81%; The observational indicators included: (1) the basic information of the donor, the amount of living bacteria in the HIF and powder. (2) Preliminary analysis of the treatment for ASD, which combined HIFT capsule with standard FMT capsule, from February to December 2021 (Clinical trial Registration Number: ChiCTR2100043929). Evaluation criteria: Trypan blue staining method was used to detect the living bacteria amount in fluid and powder. The Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the efficacy. Results: Compared with the parent donor, the standard donor was younger [(25.4±0.9) y vs. (30.7±3.2) y, t=-19.097, P=0.001] and had a lower body mass index [(19.7±0.5) kg/m[2] vs. (20.8±1.3) kg/m[2], t=-8.726, P=0.001], more in the living bacteria amount in powder [(7.47±1.52)×10[6]/g vs. (5.03±1.38)×10[6]/g, t=11.331, P=0.031], Chao index (205.4±6.8 vs. 194.2±7.2, t=10.415, P=0.001), and Shannon index (3.25±0.14 vs 2.72±0.27, t=19.465, P=0.001). The differences were statistically significant (all P<0.05). However, there were no significant differences in gender, drainage volume and total number of bacterial liquid colonies between the two groups (all P>0.05). Both the standard donor and the parent donor met the donor screening criteria, and the preparation fluid and powder met the treatment criteria. Eight patients received the treatment of HIFT combined with fecal microbiota transplantation (FMT). Preliminary statistical results showed that HIFT combined with FMT improved ABC and CARS at the 1st, 2nd, 3rd and 4th months. The differences were statistically significant (all P<0.05). No severe adverse reaction occurred. Conclusion: Based on the previous research on FMT preparation system and the clinical technology in our center, this study developed a high standard HIFT preparation system, and explored the clinical study of HIFT combined with FMT, in order to provide an innovative therapy for the treatment of diseases.}, }
@article {pmid36117371, year = {2022}, author = {Ye, C and Chen, QY and Ma, XQ and Lv, P and Yang, HL and Tian, D and Zhao, ZL and Lin, JQ and Cui, N and Li, HL and Qin, H}, title = {[Long-term outcomes of 328 patients with of autism spectrum disorder after fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {798-803}, doi = {10.3760/cma.j.cn441530-20220601-00238}, pmid = {36117371}, issn = {1671-0274}, support = {21Y11908300//Shanghai Action Plan on Science, Technology and Innovation/ ; SHDC2020CR1030B, SHDC2020CR4026//Clinical Research Plan of SHDC/ ; }, mesh = {*Autism Spectrum Disorder/etiology/therapy ; Child ; Child, Preschool ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Female ; *Gastrointestinal Diseases ; Humans ; Longitudinal Studies ; Male ; Retrospective Studies ; }, abstract = {Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of autism spectrum disorder (ASD). Methods: A longitudinal study was conducted. Clinical data from ASD patients with gastrointestinal symptoms and who underwent FMT in the Tenth People's Hospital affiliated to Tongji University or Jinling Hospital between May 2012 to May 2021 were retrospectively collected. Scores derived from the autism behavior checklist (ABC), the childhood autism rating scale (CARS), the Bristol stool form scale (BSFS), and the gastrointestinal symptom rating scale (GSRS) were analyzed at baseline and at the 1st, 3rd, 6th, 12th, 24th, 36th, 48th and 60th month after FMT. Records of any adverse reactions were collected. Generalized estimating equations were used for analysis of data on time points before and after FMT. Results: A total of 328 patients met the inclusion criteria for this study. Their mean age was 6.1±3.4 years old. The cohort included 271 boys and 57 girls. The percentage of patients remaining in the study for post-treatment follow-up at the 1st, 3rd, 12th, 24th, 36th, 48th and 60th month were as follows: 303 (92.4%), 284 (86.7%), 213 (64.9%), 190 (57.9%), 143 (43.6%), 79 (24.1%), 46 (14.0%), 31 (9.5%). After FMT, the average ABC score was significantly improved in the first 36 months and remained improved at the 48th month. However, the average score was not significantly different from baseline by the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.108). The average CARS score improved significantly during the first 48 months and remained improved at the 60th month (1st-48th month, P<0.001; 60th month, P=0.010). The average BSFS score was also significantly improved in the first 36 months (with an accompanying stool morphology that resembled type 4). This improvement was maintained at the 48th month. However, the average score was similar to baseline at the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.109). The average GSRS score was significantly improved during the first 24 months, but not afterwards (1st-24th month, P<0.001; 36th month, P=0.209; 48th month, P=0.996; 60th month, P=0.668). The adverse events recorded during treatment included abdominal distension in 21 cases (6.4%), nausea in 14 cases (4.3%), vomiting in 9 cases (2.7%), abdominal pain in 15 cases (4.6%), diarrhea in 18 cases (5.5%), fever in 13 cases (4.0%), and excitement in 24 cases (7.3%). All adverse reactions were mild to moderate and improved immediately after suspension of FMT or on treatment of symptoms. No serious adverse reactions occurred. Conclusion: FMT has satisfactory long-term efficacy and safety for the treatment of ASD with gastrointestinal symptoms.}, }
@article {pmid36117369, year = {2022}, author = {Lin, ZL and Lu, JB and Chen, QY and Cui, JQ and Ye, C and Tian, HL and Qin, HL and Li, N}, title = {[Clinical effectiveness of fecal microbiota transplantation combined with nutritional support and psychological intervention in patients with "Tetralogy of Tongji"].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {784-791}, doi = {10.3760/cma.j.cn441530-20220605-00245}, pmid = {36117369}, issn = {1671-0274}, support = {81972221//National Natural Science Foundation of China/ ; SHDC2020CR1030B//Clinical Research Plan of SHDC/ ; }, mesh = {Adolescent ; Adult ; Amenorrhea ; China ; Constipation ; Dopamine ; Fecal Microbiota Transplantation ; Female ; Fibrinogen ; *Gastrointestinal Diseases ; Humans ; Hydrocortisone ; Infant ; Longitudinal Studies ; Male ; *Malnutrition ; Middle Aged ; Norepinephrine ; Nutritional Support ; Prealbumin ; Psychosocial Intervention ; Quality of Life ; Treatment Outcome ; Young Adult ; }, abstract = {Objective: To summarize and analyze the clinical effect of fecal microbiota transplantation (FMT) combined with nutritional support and psychotherapy in patients with "Tetralogy of Tongji" (comprising chronic gastrointestinal dysfunction, mental and psychological disorders, malnutrition, and endocrine disorders). Methods: A longitudinal study was conducted. The inclusion criteria were as follows: (1) patients were under 70 years of age; (2) patients exhibited chronic gastrointestinal dysfunction (in accordance with the Rome IV diagnostic criteria for irritable bowel syndrome ie. chronic functional constipation, diarrhea, abdominal pain and abdominal distention) with onset occurring more than one year previously; (3) patients exhibited malnutrition (body mass index ≤ 18.5 kg/m[2]); (4) patients exhibited depression, anxiety, or state as diagnosed by a psychologist using the Hamilton anxiety rating scale (HAMA) and the Hamilton depression scale (HAMD); (5) patients were women of childbearing age with amenorrhea or menstrual disorder with a duration ≥6 months. Patients were excluded if they exhibited gastrointestinal bleeding, short bowel syndrome, radiation-induced intestinal injury, intestinal obstruction or inflammatory bowel disease, recurrent/metastatic tumors, systemic infectious diseases, life-threatening systemic comorbidities, intorlerate to nasojejunal, percutaneous gastrostomy / jejunostomy or FMT. The clinical data of 43 patients at Shanghai Tenth People's Hospital exhibiting the "Tetralogy of Tongji" and who received microflora transplantation combined with nutritional support and psychotherapy from June 2017 to June 2021 was prospectively collected. There were 12 males and 31 females with a mean age of 35.2±16.7 years. All 43 patients had chronic gastrointestinal dysfunction. Of these, 24 patients had depression and 19 had anxiety. There were 26 women of reproductive age, including 13 cases of menstrual disorder and 9 cases of amenorrhea. The treatment intervention was a combination of FMT (microflora solution or microflora capsule), nutritional support (enteral nutrition) and psychological intervention. The following were assessed before treatment and 1, 3, 6 months after treatment: (1) gastrointestinal function was assessed using the gastrointestinal symptoms rating scale (GSRS), where a higher score is indicative of more serious gastrointestinal symptoms, and the gastrointestinal quality of life index (GIQLI), where a higher score is indicative of higher quality of life; (2) psychological status was assessed using HAMA and HAMD scores, where a lower score is indicative of reduced severity of anxiety or depression symptoms, respectively; (3) nutritional status was assessed by measurements of total blood protein, albumin, fibrinogen and prealbumin, as well as measurements of body mass and body mass index (BMI); (4) neuroendocrine function was assessed by measurement of blood levels of cortisol, dopamine and noradrenaline, as well as menstruation in women of reproductive age. Results: The follow-up rates at 1, 3 and 6 months after treatment were 90.7% (39/43), 72.1% (31/43) and 55.8% (24/43), respectively. The total effective rate for chronic gastrointestinal dysfunction was 81.4% (35/43), of which the average GSRS score decreased from 29.35±3.56 before treatment to 18.25±2.56 in the sixth month (P<0.001). The average GIQLI score increased from 56.23±10.34 before treatment to 91.04±20.39 in the sixth month (P<0.001). All patients had malnutrition before treatment. After 6 months, their body weight had increased from 40.61±8.88 kg to 50.45±6.23 kg (P<0.001), and BMI had increased from 15.17±1.87 kg/m[2] to 19.58±1.42 kg/m[2] (P<0.001). The average total protein level was 60.99± 5.99 g/L before treatment. After 6 months, this had increased to 64.21±4.23 g/L (F=2.715, P=0.022). The average prealbumin level increased from 150.14±56.04 mg/L before treatment to 258.17±86.94 mg/L after 6 months (F=15.124, P<0.001). In this study, 24 patients with depression/depressed state were included. After treatment, the average HAMD score in these patients decreased from 22.79±6.63 before treatment to 9.92±7.24 after 6 months (P<0.001). There were 19 patients with anxiety disorder/anxiety state. After treatment, the average HAMA score in these patients decreased from 17.15±4.34 before treatment to 7.73±4.10 after 6 months (P<0.001). Observing the endocrine efficacy of 26 women of childbearing age, it was found that the effective rate of this treatment on endocrine regulation was 69.2% (18/26). Although there was no significant change in blood cortisol levels after 6 months, average blood dopamine levels decreased from 32.91±10.65 nmol/L before treatment to 13.02±5.58 nmol/L after 6 months (P<0.001). Average blood norepinephrine levels decreased from 49.75±15.23 ng/L before treatment to 19.21±9.58 ng/L after 6 months (P<0.001). Conclusion: The strategy of FMT combined with nutritional support and psychological intervention is effective in improving the symptoms of the "Tetralogy of Tongji".}, }
@article {pmid36117367, year = {2022}, author = {Chen, QY and Lu, JB and Qin, HL and Li, N}, title = {[Clinical significance and intervention strategy of gastrointestinal psychiatry].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {771-776}, doi = {10.3760/cma.j.cn441530-20220601-00236}, pmid = {36117367}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; SHDC2020CR4026//Clinical Research Plan of SHDC/ ; 21Y11908300//Shanghai Action Plan on Science, Technology and Innovation/ ; }, mesh = {*Gastrointestinal Diseases/drug therapy ; Humans ; *Mental Disorders/therapy ; Prebiotics ; *Probiotics ; *Psychiatry ; }, abstract = {With the development of global economy and society,the number of patients who suffer from functional gastrointestinal disorders (FGID) and mental illness is growing. In recent years, a substantial amount of high-quality research evidence shows that these two kinds of diseases often coexist, and they are mutually causal, and their common pathophysiology is the abnormal interaction of "bacteria-gut-brain axis". In clinical practice, there are some problems, such as insufficient recognition and attention of both doctors and patients to its clinical manifestations, lack of understanding of pathophysiological mechanism, and lack of overall and integrated views of intervention methods, which may be the main factors of poor curative effect at present. Therefore, according to the global research progress and the author's clinical experience, we put forward a new viewpoint of "gastrointestinal psychiatry", it concluded that clinical intervention strategies needed to include dietary and lifestyle changes as well as multidisciplinary interventions such as probiotics, prebiotic, fecal microbiota transplantation and cognitive psychology. On the basis of gastrointestinal psychiatry, this paper systematically elaborated the diagnosis and treatment of this kind of diseases.}, }
@article {pmid36117366, year = {2022}, author = {Qin, HL and Chen, QY and Li, N}, title = {[Further improve the standardization construction and development level of fecal microbiota transplantation (FMT) in China].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {766-770}, doi = {10.3760/cma.j.cn441530-20220601-00237}, pmid = {36117366}, issn = {1671-0274}, support = {81972221//National Natural Science Foundation of China/ ; SHDC2020CR1030B//Clinical Research Plan of SHDC/ ; }, mesh = {Capsules ; China ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Reference Standards ; }, abstract = {In the past ten years, the clinical application of fecal microbiota transplantation (FMT) in the treatment of intestinal and extraintestinal diseases has attracted much attention. In China, there are more than 300 hospitals that have developed FMT, but the development of FMT is still in its early stage. The clinical practice of FMT needs to form a standardized system, including management of donors and acceptors, preparation of capsules containing certain gut bacteria, evaluation of effectiveness, and study of fecal microbiota and disease. In order to promote the establishment of the standard system of FMT and the healthy development of FMT, this paper expounds the establishment of the standardization of domestic flora transplantation according to the relevant literature, as well as the experience of 10000 cases and 95300 times of FMT in our center.}, }
@article {pmid36117365, year = {2022}, author = {,  and , }, title = {[Chinese expert consensus on screening and management of fecal microbiota transplantation donors (2022 edition)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {757-765}, doi = {10.3760/cma.j.cn441530-20220606-00246}, pmid = {36117365}, issn = {1671-0274}, support = {81972221, 82100698//National Natural Science Foundation/ ; SHDC2020CR1030B//Major Clinical Research Projects of the Three-year Action Plan for Clinical Innovation of Shanghai Shenkang Hospital Development Center/ ; }, mesh = {China ; Consensus ; *Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) has been recommended by clinical practical guidelines and consensus for the treatment of a variety of intestinal diseases, but in more and more medical institutions trying to develop this technology in clinical practice, how to screen and manage donors has become an urgent need for regulation. In view of this, based on evidence-based medical evidence, Society of Parenteral and Enteral Nutrition of Chinese Medical Association and Microecology Professional Committee of Shanghai Preventive Medicine Association jointly formulate an expert consensus on the screening and management of donors, including screening on the internet and in clinic, evaluation and selection during donation, establishment of the standard of donor management, the follow-up system and the professional support system, with a view to improving the quality of microbiota transplantation donors, reducing adverse events, and promoting the standardized clinical application of FMT.}, }
@article {pmid36117364, year = {2022}, author = {,  and ,  and , }, title = {[Expert consensus on clinical application management of fecal microbiota transplantation (2022 edition)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {25}, number = {9}, pages = {747-756}, doi = {10.3760/cma.j.cn441530-20220725-00324}, pmid = {36117364}, issn = {1671-0274}, mesh = {Consensus ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Intestinal Diseases ; }, abstract = {Fecal microbiota transplantation (FMT) is to transplant the functional intestinal bacteria from human feces into the intestinal tract of patients, reconstruct the new intestinal flora and treat intestinal and extra-intestinal diseases. During the past 10 years, FMT has made a breakthrough in the treatment of intestinal and extra-intestinal diseases, and provided a brand-new strategy to the treatment of intestinal and extra-intestinal diseases. In view of the fact that FMT lacks a unified clinical management standard at home and abroad, relevant regulations and policies still need to be improved, and clinical application experience still needs to be accumulated, the National Institute of Hospital Administration, National Health Commission commissioned a clinical FMT expert working group to organize experts in related fields. Based on thorough analysis of relevant literature, policies and norms internationally, as well as the mature experience of FMT in many medical institutions in China, an expert consensus for clinical management of FMT in medical institutions is compiled to further strengthen its clinical application and standard management, so as to improve the safety and efficacy of FMT.}, }
@article {pmid36116455, year = {2022}, author = {Ianiro, G and Mullish, BH and Iqbal, TH and Terveer, EM and Baunwall, SMD and Link, A and Sokol, H and Kupcinskas, J and Masucci, L and Sanguinetti, M and Vehreschild, MJGT and Hvas, CL and Keller, JJ and Gasbarrini, A and Kujiper, EJ and Cammarota, G}, title = {Minimising the risk of monkeypox virus transmission during faecal microbiota transplantation: recommendations from a European expert panel.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {11}, pages = {979-980}, pmid = {36116455}, issn = {2468-1253}, mesh = {*Clostridioides difficile ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Monkeypox virus ; Mpox, Monkeypox ; }, }
@article {pmid36114204, year = {2022}, author = {Pu, Y and Zhang, Q and Tang, Z and Lu, C and Wu, L and Zhong, Y and Chen, Y and Hashimoto, K and Luo, Y and Liu, Y}, title = {Correction: Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation.}, journal = {Translational psychiatry}, volume = {12}, number = {1}, pages = {387}, doi = {10.1038/s41398-022-02168-6}, pmid = {36114204}, issn = {2158-3188}, }
@article {pmid36110348, year = {2022}, author = {Abdelghafar, YA and AbdelQadir, YH and Motawea, KR and Nasr, SA and Omran, HAM and Belal, MM and Elhashash, MM and AbdelAzim, AA and Shah, J}, title = {Efficacy and safety of fecal microbiota transplant in irritable bowel syndrome: An update based on meta-analysis of randomized control trials.}, journal = {Health science reports}, volume = {5}, number = {5}, pages = {e814}, pmid = {36110348}, issn = {2398-8835}, abstract = {BACKGROUND AND AIMS: Fecal microbiota transfer (FMT) is a potential treatment for irritable bowel syndrome (IBS). Several randomized trials have tested FMT effects using different routes of administration, doses, and sample sizes. We aim to assess the overall efficacy of FMT for IBS patients and the safety of the intervention.<br><br>METHODS: We systematically searched four databases for randomized control trials that studied the efficacy and safety of FMT in IBS patients.<br><br>RESULTS: We included 8 randomized trials (472 patients) that compared FMT with placebo in IBS patients. Pooled results showed no statistically significant difference between FMT and control groups in the overall change in IBS symptom severity (IBS-SSS) at 1 month (p&#x2009;=&#x2009;0.94), 3/4 months (p&#x2009;=&#x2009;0.82), and at the end of trials (p&#x2009;=&#x2009;0.67). No significant difference in the total number of respondents between the FMT and control groups (risk ratios&#x2009;=&#x2009;1.84, [95% confidence interval (CI)&#x2009;=&#x2009;0.82-2.65], p&#x2009;=&#x2009;0.19). Although the oral route of administration showed a significant difference in the number of respondents (p&#x2009;=&#x2009;0.004), there was no statistically significant difference in the IBS-SSS when subgrouping the oral route of administration (mean difference&#x2009;=&#x2009;47.57, [95% CI&#x2009;=&#x2009;-8.74-103.87], p&#x2009;=&#x2009;0.10).<br><br>CONCLUSION: FMT is not an effective treatment to relieve all the symptoms of IBS. Even in the groups that showed relatively significant improvement after FMT, the effect was proven to wear off over time and the re-administration carries a low success rate. Future research should consider different bacterial-based interventions such as probiotics or specific antibiotics.}, }
@article {pmid36109641, year = {2022}, author = {Lavelle, A and Sokol, H}, title = {Understanding and predicting the efficacy of FMT.}, journal = {Nature medicine}, volume = {28}, number = {9}, pages = {1759-1760}, pmid = {36109641}, issn = {1546-170X}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Treatment Outcome ; }, }
@article {pmid36109637, year = {2022}, author = {Ianiro, G and Punčochář, M and Karcher, N and Porcari, S and Armanini, F and Asnicar, F and Beghini, F and Blanco-Míguez, A and Cumbo, F and Manghi, P and Pinto, F and Masucci, L and Quaranta, G and De Giorgi, S and Sciumè, GD and Bibbò, S and Del Chierico, F and Putignani, L and Sanguinetti, M and Gasbarrini, A and Valles-Colomer, M and Cammarota, G and Segata, N}, title = {Variability of strain engraftment and predictability of microbiome composition after fecal microbiota transplantation across different diseases.}, journal = {Nature medicine}, volume = {28}, number = {9}, pages = {1913-1923}, pmid = {36109637}, issn = {1546-170X}, support = {R01 CA230551/CA/NCI NIH HHS/United States ; U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; *Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is highly effective against recurrent Clostridioides difficile infection and is considered a promising treatment for other microbiome-related disorders, but a comprehensive understanding of microbial engraftment dynamics is lacking, which prevents informed applications of this therapeutic approach. Here, we performed an integrated shotgun metagenomic systematic meta-analysis of new and publicly available stool microbiomes collected from 226 triads of donors, pre-FMT recipients and post-FMT recipients across eight different disease types. By leveraging improved metagenomic strain-profiling to infer strain sharing, we found that recipients with higher donor strain engraftment were more likely to experience clinical success after FMT (P = 0.017) when evaluated across studies. Considering all cohorts, increased engraftment was noted in individuals receiving FMT from multiple routes (for example, both via capsules and colonoscopy during the same treatment) as well as in antibiotic-treated recipients with infectious diseases compared with antibiotic-naïve patients with noncommunicable diseases. Bacteroidetes and Actinobacteria species (including Bifidobacteria) displayed higher engraftment than Firmicutes except for six under-characterized Firmicutes species. Cross-dataset machine learning predicted the presence or absence of species in the post-FMT recipient at 0.77 average AUROC in leave-one-dataset-out evaluation, and highlighted the relevance of microbial abundance, prevalence and taxonomy to infer post-FMT species presence. By exploring the dynamics of microbiome engraftment after FMT and their association with clinical variables, our study uncovered species-specific engraftment patterns and presented machine learning models able to predict donors that might optimize post-FMT specific microbiome characteristics for disease-targeted FMT protocols.}, }
@article {pmid36109636, year = {2022}, author = {Schmidt, TSB and Li, SS and Maistrenko, OM and Akanni, W and Coelho, LP and Dolai, S and Fullam, A and Glazek, AM and Hercog, R and Herrema, H and Jung, F and Kandels, S and Orakov, A and Thielemann, R and von Stetten, M and Van Rossum, T and Benes, V and Borody, TJ and de Vos, WM and Ponsioen, CY and Nieuwdorp, M and Bork, P}, title = {Drivers and determinants of strain dynamics following fecal microbiota transplantation.}, journal = {Nature medicine}, volume = {28}, number = {9}, pages = {1902-1912}, pmid = {36109636}, issn = {1546-170X}, mesh = {*Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome/genetics ; Gastrointestinal Tract ; Humans ; *Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor-recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.}, }
@article {pmid36107983, year = {2022}, author = {Koo, H and Morrow, CD}, title = {Time series strain tracking analysis post fecal transplantation identifies individual specific patterns of fecal dominant donor, recipient, and unrelated microbial strains.}, journal = {PloS one}, volume = {17}, number = {9}, pages = {e0274633}, pmid = {36107983}, issn = {1932-6203}, support = {P30 CA013148/CA/NCI NIH HHS/United States ; }, mesh = {*Anti-Bacterial Agents ; *Fecal Microbiota Transplantation ; Feces ; Nucleotides ; Time Factors ; }, abstract = {BACKGROUND: Fecal microbial transplantation (FMT) has been used with the therapeutic intent to change the functions of the gut microbial community in metabolism and host immunity. For most of these therapies, the recipients are not given antibiotics to eliminate the microbial community prior to transplant with donor fecal microbes resulting in the initial gut microbial community following FMT consisting of a consortium of donor and recipient microbes. The detailed analysis of the fecal samples from these FMT over time provides a unique opportunity to study the changes in the gut microbial strain community that occurs following the introduction of new microbial strains (donor) into an established community (recipient).<br><br>METHODS: In this study, we have metagenomic data set consisting of 5 FMT that contained donor, recipient and recipient post FMT taken multiple times for periods up to 535 days after the FMT. We used two established strain tracking methods, Window-based Single Nucleotide Variant (SNV) Similarity (WSS) and StrainPhlAn, to determine the presence of donor and recipient microbial strains following FMT. To assess recombination between donor and recipient strains of Bacteroides vulgatus post FMT, we used BLAST+ to analyze the data sets for Bacteroidales-specific antimicrobial proteins (BSAP-3) that have known functions to restrict species specific replication.<br><br>RESULTS: We found that Alistipes onderdonkii, Alistipes shahii, Alistipes putredinis, and Parabacteroides merdae, all had patterns post FMT consisting of either dominant donor or recipient microbial strains in the feces. In contrast, the analysis of Bacteroides spp. in five FMT pairs revealed inter-individual oscillation over time with the appearance of either donor or recipient fecal strain dominance. In some instances, B. vulgatus and B. uniformis were also identified after FMT that were not related to either the donor or recipient. Finally, in one of the FMT, we identified a distinct B. vulgatus strain post-FMT that matched the pre-FMT strain but was BSAP-3 positive, suggesting a possible recombination event between the donor and recipient strains.<br><br>CONCLUSION: The complex oscillating patterns of the appearance of fecal dominant donor, recipient or unrelated strains following extended times post FMT provide new insights into the dynamics of the microbial community interactions with the recipients following FMT. The result from our analysis has implications for the use of FMT to predictably change the biological functions of the gut community in metabolism and host immunity.}, }
@article {pmid36106327, year = {2022}, author = {Shi, D and Turroni, S and Gong, L and Wu, W and Yim, HCH}, title = {Editorial: Manipulation of gut microbiota as a key target to intervene on the onset and progression of digestive system diseases.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {999005}, pmid = {36106327}, issn = {2296-858X}, }
@article {pmid36105887, year = {2022}, author = {Deluce, J and Maleki Vareki, S and Fernandes, R}, title = {The role of gut microbiome in immune modulation in metastatic renal cell carcinoma.}, journal = {Therapeutic advances in medical oncology}, volume = {14}, number = {}, pages = {17588359221122714}, pmid = {36105887}, issn = {1758-8340}, abstract = {Treatment of metastatic renal cell carcinomas (mRCC) has drastically improved since the advent of immunotherapy with immune checkpoint inhibitors (ICIs), with a significant proportion of patients achieving durable responses. While this has revolutionized treatment and improved outcomes for mRCC patients, a large subset of patients still does not respond to treatment with ICIs. Moreover, ICIs can induce various immune-related adverse events, limiting their use in many patients. Therefore, there is a need to identify the predictive biomarkers of both efficacy and toxicity associated with ICIs, which would allow for a more personalized approach and help with clinical decision-making. This review aims to explore the role of the gut microbiome in RCC to overcome primary resistance and predict response to treatment with ICIs. First, current therapeutic strategies and mechanisms of action of ICI therapies for RCC treatment will be reviewed. With the technological development of shotgun whole-genome sequencing, the gut microbiome has emerged as an exciting field of research within oncology. Thus, the role of the microbiome and its bidirectional interaction with ICIs and other drugs will be explored, with a particular focus on the microbiome profile in RCC. Lastly, the rationale for future clinical interventions to overcome resistance to ICIs using fecal microbiota transplantation in patients with RCC will be presented.}, }
@article {pmid36103991, year = {2022}, author = {Wang, Y and Zhang, S and Borody, TJ and Zhang, F}, title = {Encyclopedia of fecal microbiota transplantation: a review of effectiveness in the treatment of 85 diseases.}, journal = {Chinese medical journal}, volume = {135}, number = {16}, pages = {1927-1939}, pmid = {36103991}, issn = {2542-5641}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; Dysbiosis/therapy ; *Gastrointestinal Microbiome ; Feces ; *Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) has been used as a core therapy for treating dysbiosis-related diseases by remodeling gut microbiota. The methodology and technology for improving FMT are stepping forward, mainly including washed microbiota transplantation (WMT), colonic transendoscopic enteral tubing (TET) for microbiota delivery, and purified Firmicutes spores from fecal matter. To improve the understanding of the clinical applications of FMT, we performed a systematic literature review on FMT published from 2011 to 2021. Here, we provided an overview of the reported clinical benefits of FMT, the methodology of processing FMT, the strategy of using FMT, and the regulations on FMT from a global perspective. A total of 782 studies were included for the final analysis. The present review profiled the effectiveness from all clinical FMT uses in 85 specific diseases as eight categories, including infections, gut diseases, microbiota-gut-liver axis, microbiota-gut-brain axis, metabolic diseases, oncology, hematological diseases, and other diseases. Although many further controlled trials will be needed, the dramatic increasing reports have shown the promising future of FMT for dysbiosis-related diseases in the gut or beyond the gut.}, }
@article {pmid36103760, year = {2022}, author = {Hu, C and Li, J and Liu, M and Lam, PKS and Chen, L}, title = {Young fecal transplantation modulates the visual toxicity of perfluorobutanesulfonate in aged zebrafish recipients.}, journal = {Aquatic toxicology (Amsterdam, Netherlands)}, volume = {251}, number = {}, pages = {106295}, doi = {10.1016/j.aquatox.2022.106295}, pmid = {36103760}, issn = {1879-1514}, mesh = {Animals ; Fecal Microbiota Transplantation ; Female ; Fluorocarbons ; Male ; Proteome ; Proteomics ; Sulfonic Acids ; *Water Pollutants, Chemical/toxicity ; *Zebrafish ; }, abstract = {Perfluorobutanesulfonate (PFBS) is an emerging pollutant of potent toxicity to impair visual system. Previous studies highlighted the applicability of gut microbiota manipulation to mitigate the toxicities of PFBS. However, it remains unknown whether transplantation of whole fecal microbiota to PFBS-disturbed gut can restore the health of the recipient animals, especially for aged fish that are of high susceptibility. In the present study, aged zebrafish of 3 years old were first transplanted with feces from young counterparts and then exposed to environmentally relevant concentrations of PFBS. After exposure, toxic effects of PFBS on visual system of aged zebrafish were elucidated based on transcriptional, proteomic, biochemical, histological, and behavioral evidences. In addition, interaction between young fecal transplant and innate visual toxicity of PFBS was further explored in the aged. The results showed that PFBS singular exposure induced lipid peroxidation (by 1.9-fold) in aged male eyes, which were alleviated by young fecal transplantation. PFBS also disturbed the retinal structure of the aged, which was characterized by increases in plexiform layers, but decreases in ganglion neuron number (by 26.8% and 26.0% in males and females, respectively) and optic nerve width (by 14.1% and 12.7% in males and females, respectively). It was unexpected that young fecal transplant was very potent in re-organizing the histological assembly of aged eyes regardless of PFBS coexposure, underlining the intimate interplay between gut and retina. Proteomic profiling provided more clues about the visual toxicology mechanism of PFBS, which was found to typically interfere with synaptic neurotransmission occurring in plexiform layers. However, proteome perturbation of aged eyes by PFBS exposure was effectively shifted by the transplantation of young feces towards the control phenotype, suggesting the high ameliorative potential of young fecal transplantation along the gut-retina axis. Overall, the present study pinpoints the potent visual toxicity of PFBS in aged animals and highlights the efficacy of young fecal transplant to regulate the inherent toxicity of PFBS. Future studies are necessitated to sequence the gut microbiota and unveil the underlying interactive routes between gut microbes and visual system.}, }
@article {pmid36100957, year = {2022}, author = {Jia, L and Weng, S and Wu, J and Tian, X and Zhang, Y and Wang, X and Wang, J and Yan, D and Wang, W and Fang, F and Zhu, Z and Qiu, C and Zhang, W and Xu, Y and Wan, Y}, title = {Preexisting antibodies targeting SARS-CoV-2 S2 cross-react with commensal gut bacteria and impact COVID-19 vaccine induced immunity.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2117503}, pmid = {36100957}, issn = {1949-0984}, mesh = {Animals ; Antibodies, Monoclonal ; Antibodies, Viral ; *COVID-19/prevention &amp; control ; COVID-19 Vaccines ; Escherichia coli ; *Gastrointestinal Microbiome ; Humans ; Mice ; SARS-CoV-2 ; *Viral Vaccines ; }, abstract = {The origins of preexisting SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the preexisting S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by preexisting antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we demonstrated that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 reactive monoclonal antibodies were isolated from naïve SPF mice and were proven to cross-react with commensal gut bacteria collected from both human and mouse. A variety of cross-reactive microbial proteins were identified using LC-MS, of which E. coli derived HSP60 and HSP70 proteins were confirmed to be able to bind to one of the isolated monoclonal antibodies. Mice with high levels of preexisting S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of preexisting S2 and P144-specific antibodies correlated positively with RBD binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Collectively, our study revealed an alternative origin of preexisting S2-targeted antibodies and disclosed a previously neglected aspect of the impact of gut microbiota on host anti-SARS-CoV-2 immunity.}, }
@article {pmid36100953, year = {2022}, author = {Bai, X and Sun, Y and Li, Y and Li, M and Cao, Z and Huang, Z and Zhang, F and Yan, P and Wang, L and Luo, J and Wu, J and Fan, D and Chen, H and Zhi, M and Lan, P and Zeng, Z and Wu, X and Miao, Y and Zuo, T}, title = {Landscape of the gut archaeome in association with geography, ethnicity, urbanization, and diet in the Chinese population.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {147}, pmid = {36100953}, issn = {2049-2618}, mesh = {Adult ; Archaea ; Bacteria/genetics ; Diet ; Ethnicity ; *Gastrointestinal Microbiome/genetics ; Geography ; Humans ; *Urbanization ; }, abstract = {BACKGROUND AND AIMS: The human gut is home to a largely underexplored microbiome component, the archaeome. Little is known of the impact of geography, urbanization, ethnicity, and diet on the gut archaeome in association with host health. We aim to delineate the variation of the human gut archaeome in healthy individuals and its association with environmental factors and host homeostasis.<br><br>METHODS: Using metagenomic sequencing, we characterized the fecal archaeomes of 792 healthy adult subjects from 5 regions in China, spanning 6 ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), consisting of both urban and rural residents for each ethnicity. In addition, we sampled 119 host variables (including lifestyle, diet, and blood parameters) and interrogated the influences of those factors, individually and combined, on gut archaeome variations.<br><br>RESULTS: Population geography had the strongest impact on the gut archaeome composition, followed by urbanization, dietary habit, and ethnicity. Overall, the metadata had a cumulative effect size of 11.0% on gut archaeome variation. Urbanization decreased both the &#x3b1;-diversity (intrinsic microbial diversity) and the &#x3b2;-diversity (inter-individual dissimilarities) of the gut archaeome, and the archaea-to-bacteria ratios in feces, whereas rural residents were enriched for Methanobrevibacter smithii in feces. Consumption of buttered milk tea (a characteristic diet of the rural Zang population) was associated with increased abundance of M. smithii. M. smithii was at the central hub of archaeal-bacterial interactions in the gut microecology, where it was positively correlated with the abundances of a multitude of short chain fatty acid (SCFA)-producing bacteria (including Roseburia faecis, Collinsella aerofaciens, and Prevotella copri). Moreover, a decreased abundance of M. smithii was associated with increased human blood levels of cholinesterase in the urban population, coinciding with the increasing prevalence of noncommunicable diseases (such as dementia) during urbanization.<br><br>CONCLUSIONS: Our data highlight marked contributions of environmental and host factors (geography, urbanization, ethnicity, and habitual diets) to gut archaeome variations across healthy individuals, and underscore the impact of urbanization on the gut archaeome in association with host health in modern society. Video Abstract.}, }
@article {pmid36100450, year = {2022}, author = {Pipek, B and Valentová, H and Fojtík, P and Urban, O}, title = {Faecal microbiota transplantation in the treatment of recurrent intestinal Clostridioides difficile infection - a ten-year single-center experience.}, journal = {Casopis lekaru ceskych}, volume = {161}, number = {3-4}, pages = {126-130}, pmid = {36100450}, issn = {0008-7335}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Clostridium Infections/etiology/microbiology ; Ecosystem ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Humans ; Male ; Prospective Studies ; Recurrence ; Young Adult ; }, abstract = {Clostridioides difficile (Clostridium difficile in older taxonomy) is a gram-positive anaerobic and bacteria enabled by endospores. Clostridioides difficile is currently the main cause of nosocomial infections in developed countries. Due to the high probability of developing bacterial resistance to treatment and the numerous recurrences in multiple chronic conditions in older adults of our society it causes a widespread medical problem. Faecal microbiota transplantation (FMT) is a highly effective method for treating recurrent intestinal Clostridioides difficile infections (CDI). With this method the potential mechanism of effect is the transmission of a complex intestinal ecosystem, including vital microorganisms, from the donor to the recipient. Presenting the results of monocentric prospective monitoring: Primary aim of the study was to evaluate long-term remission (the continued absence of clinical manifestations of CDI 3 months after FMT administration). The secondary aim of the study was to monitor the short-term remission in the 7 days after FMT administration. Demographic data, information about CDI and the details of therapy were obtained and completed by the treating physician of each patient or by targeted questioning of the patient or their family. We used clinical monitoring to determine the effect of the treatment. The examinations of stool donors and the preparation for a faecal microbiota transplantation were performed according to the currently valid guidelines of the Czech Society of Infectious Diseases for the treatment of the recurrent bacterial infection Clostridioides difficile with faecal microbiota transplantation. The follow-ups took place from February 2011 to July 2021 in the gastroenterology department at the AGEL Ostrava-Vítkovice Hospital and included 116 patients with their first and subsequent recurrence of CDI that were treated with faecal bacteriotherapy. The median age of our patients was 71 years old (the youngest was 19 years old, the oldest 103 years old). 69 women and 47 men took part in the study. 56 patients had their first recurrence of CDI, 41 had a second attack, and 20 patients had a third and subsequent recurrences. In 62 patients (53.4 %), the route of FMT administration was a local enema into the left colon. With 37 patients (31.9 %) we used a colonoscopy after standard anterograde bowel preparation. With 12 patients (10.3 %) gastroscopy administration (deep into the duodenum) was used. 4 patients (3.5 %) were given a nasoenteral tube and one patient (0.9 %) was administered FMT per percutaneous endoscopic gastrostomy (PEG). We applied a frozen universal donor FMT in 81 patients (69.8 %), and a freshly prepared FMT from a person living in the same household was used in 35 patients (30.1 %). The secondary endpoint (the absence of clinical manifestations of CDI within 7 days of FMT administration) was achieved with 102 patients (87.9 %) in our study. The fulfilment of the primary endpoint (the development of long-term remission) was observed with 93 patients (80.2 %). An early administration of FMT appears to be a significant predictor of treatment effect (p = 0.05; OR 5.11; 95% CI 1.65-15.8). Faecal microbiota transplantation is an effective and safe therapy for recurrent intestinal Clostridioides difficile infection, and it respects the up-to-date guidelines for treatment. Of the 116 patients included in our study with first and subsequent CDI, we achieved long-term remission in 80.2 % of them. An early administration of FMT appears to be a significant predictor of treatment effect.}, }
@article {pmid36099923, year = {2022}, author = {Spindler, MP and Siu, S and Mogno, I and Li, Z and Yang, C and Mehandru, S and Britton, GJ and Faith, JJ}, title = {Human gut microbiota stimulate defined innate immune responses that vary from phylum to strain.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {10}, pages = {1481-1498.e5}, pmid = {36099923}, issn = {1934-6069}, support = {R01 DK123749/DK/NIDDK NIH HHS/United States ; T32 GM146636/GM/NIGMS NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; F30 DK124978/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Immunity, Innate ; Toll-Like Receptor 2 ; Toll-Like Receptor 4 ; }, abstract = {The potential of commensal bacteria to modulate host immunity remains largely uncharacterized, largely due to the vast number of strains that comprise the human gut microbiota. We have developed a screening platform to measure the innate immune responses of myeloid cells to 277 bacterial strains isolated from the gut microbiota of healthy individuals and those with inflammatory bowel diseases. The innate immune responses to gut-derived bacteria are as strong as those toward pathogenic bacteria, and they vary from phylum to strain. Myeloid cells differentially rely upon innate receptors TLR2 or TLR4 to sense taxa, with differential sensing of Bacteroidetes and Proteobacteria that predict in vivo functions. These innate immune responses can be modeled using combinations of up to 8 Toll-like receptor (TLR) agonists. Furthermore, the immunogenicity of strains is stable over time and following fecal microbiota transplantation into new human recipients. Collectively, this high-throughput approach provides an insight into how commensal microorganisms shape innate immune phenotypes.}, }
@article {pmid36094098, year = {2023}, author = {Vasiliu, O}, title = {Is fecal microbiota transplantation a useful therapeutic intervention for psychiatric disorders? A narrative review of clinical and preclinical evidence.}, journal = {Current medical research and opinion}, volume = {39}, number = {1}, pages = {161-177}, doi = {10.1080/03007995.2022.2124071}, pmid = {36094098}, issn = {1473-4877}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Depressive Disorder, Major ; *Alcoholism ; *Mental Disorders/therapy ; Anxiety Disorders ; }, abstract = {The therapeutic management of psychiatric disorders is currently confronted with a critical need to find new therapeutic interventions due to the high rates of non-responsivity or low responsivity in the key pathologies, e.g. schizophrenia spectrum disorders, alcohol use disorders, or major depressive disorder. The modulation of intestinal microbiota has been explored in various organic and psychiatric dysfunctions, with different degrees of success. However, this type of intervention may represent a helpful add-on at a conceptual level since it does not associate negative pharmacokinetics interactions, significant adverse events, or risk for non-adherence in the long term. Oral administration of pre-, pro-, or synbiotics, and especially the treatment with fecal microbiota transplantation (FMT), are methods still in their early research phase for patients with psychiatric disorders, therefore an exploration of data regarding the potential benefits and adverse events of FMT was considered necessary. In order to accomplish this purpose, the available results of research dedicated to each category of psychiatric disorders, starting with depressive and anxiety disorders, continuing with schizophrenia, substance use disorders, and finishing with disorders diagnosed during childhood, were presented in this paper. Seven clinical trials, 16 preclinical studies, three meta-analyses/systematic reviews, and six case reports, all of these representing ten distinct categories of psychiatric disorders or manifestations, have been reviewed. Mood disorders, anxiety disorders, and alcohol dependence have been the most extensively investigated clinical entities from the FMT efficacy and tolerability perspective, and reviewed data are generally promising. Based on the current status of research, FMT may be considered a helpful intervention in specific psychiatric pathologies. Still, this review showed that most of the information is derived from entirely preclinical studies. Therefore, clinical trials with sound methodology and more participants are needed to clarify FMT's benefits and risks in psychiatric disorders.}, }
@article {pmid36093611, year = {2022}, author = {Korpela, K and de Vos, WM}, title = {Infant gut microbiota restoration: state of the art.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2118811}, pmid = {36093611}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents ; Cesarean Section ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Pregnancy ; }, abstract = {The gut microbiota has a central role in the programming of the host's metabolism and immune function, with both immediate and long-term health consequences. Recent years have witnessed an accumulation of understanding of the process of the colonization and development of the gut microbiota in infants. The natural gut microbiota colonization during birth is frequently disrupted due to C-section birth or intrapartum or postpartum antibiotic exposure, and consequently aberrant gut microbiota development is common. On a positive note, research has shown that restoration of normal gut microbiota development is feasible. We discuss here the current understanding of the infant microbiota, provide an overview of the sources of disturbances, and critically evaluate the evidence on early life gut microbiota restoration for improved health outcomes by analyzing published data from infant gut microbiota restoration studies.}, }
@article {pmid36093568, year = {2022}, author = {Li, Z and Zhang, Y and Hong, W and Wang, B and Chen, Y and Yang, P and Zhou, J and Fan, J and Zeng, Z and Du, S}, title = {Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma Via STING signaling.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2119055}, pmid = {36093568}, issn = {1949-0984}, mesh = {Animals ; *Carcinoma, Hepatocellular/radiotherapy ; Dysbiosis/therapy ; *Gastrointestinal Microbiome ; Immunity ; *Liver Neoplasms/radiotherapy ; Mice ; Nucleotidyltransferases/metabolism ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Studies of the gut-liver axis have enhanced our understanding of the pathophysiology of various liver diseases and the mechanisms underlying the regulation of the effectiveness of therapies. Radiotherapy (RT) is an important therapeutic option for patients with unresectable hepatocellular carcinoma (HCC). However, the role of the microbiome in regulating the response to RT remains unclear. The present study characterizes the gut microbiome of patients responsive or non-responsive to RT and investigates the molecular mechanisms underlying the differences in patient response. We collected fecal samples for 16S rRNA sequencing from a prospective longitudinal trial of 24 HCC patients receiving RT. We used fecal microbiota transplantation (FMT), flow cytometry, and transcriptome sequencing to explore the effects of dysbiosis on RT. We also examined the role of stimulator of interferon genes (STING) in RT-associated antitumor immune responses mediated by gut microbiota in STING- (Tmem173[-/-]) and cGAS-knockout (Mb21d1[-/-]) mouse models. We propose that primary resistance to RT could be attributed to the disruption of the gut microbiome. Mechanistically, gut microbiome dysbiosis impairs antitumor immune responses by suppressing antigen presentation and inhibiting effector T cell functions through the cGAS-STING-IFN-I pathway. Cyclic-di-AMP - an emerging second messenger of bacteria - may act as a STING agonist and is thus a potential target for the prediction and modulation of responses to RT in HCC patients. Our study highlights the therapeutic potential of modulating the gut microbiome in HCC patients receiving RT and provides a new strategy for the radiosensitization of liver cancer.}, }
@article {pmid36091491, year = {2022}, author = {Zhang, F and Zuo, T and Wan, Y and Xu, Z and Cheung, C and Li, AY and Zhu, W and Tang, W and Chan, PKS and Chan, FKL and Ng, SC}, title = {Multi-omic analyses identify mucosa bacteria and fecal metabolites associated with weight loss after fecal microbiota transplantation.}, journal = {Innovation (Cambridge (Mass.))}, volume = {3}, number = {5}, pages = {100304}, pmid = {36091491}, issn = {2666-6758}, abstract = {Fecal microbiota transplantation (FMT) has shown promising results in animal models of obesity, while results in human studies are inconsistent. We aimed to determine factors associated with weight loss after FMT in nine obese subjects using serial multi-omics analysis of the fecal and mucosal microbiome. The mucosal microbiome, fecal microbiome, and fecal metabolome showed individual clustering in each subject after FMT. The colonic microbiome in patients showed more marked variance after FMT compared with the duodenal microbiome, characterized by an increased relative abundance of Bacteroides. Subjects who lost weight after FMT sustained enrichment of Bifidobacterium bifidum and Alistipes onderdonkii in the duodenal, colonic mucosal, and fecal microbiome and increased levels of phosphopantothenate biosynthesis and fecal metabolite eicosapentaenoic acid (EPA), compared with those without weight loss. Fecal levels of amino acid metabolism-associated were positively correlated with the fecal abundance of B. bifidum, and fatty acid metabolism-associated metabolites showed positive correlations with A. onderdonkii. We report for the first time the individualized response of fecal and mucosa microbiome to FMT in obese subjects and highlight that FMT is less capable of shaping the small intestine microbiota. These findings contribute to personalized microbe-based therapies for obesity.}, }
@article {pmid36088803, year = {2022}, author = {Cassidy, H and Schuele, L and Niesters, HG and Van Leer-Buter, C and Lizarazo-Forero, E}, title = {Genomic characterization of coxsackievirus A22 from a regional university hospital in the Netherlands.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {156}, number = {}, pages = {105272}, doi = {10.1016/j.jcv.2022.105272}, pmid = {36088803}, issn = {1873-5967}, mesh = {*Coxsackievirus Infections/epidemiology ; *Enterovirus ; *Enterovirus Infections/epidemiology ; Genomics ; Genotype ; Hospitals ; Humans ; Netherlands/epidemiology ; Phylogeny ; Sewage ; }, abstract = {BACKGROUND: Enteroviruses are highly diverse with a wide spectrum of genotypes and clinical manifestations. Coxsackievirus A22 (CVA22) has been detected globally from sewage surveillance; however, currently there is limited information on its prevalence in patients, as well as available genomic data.<br><br>OBJECTIVE: We aimed to provide genomic and relative frequency data on CVA22 from a regional hospital perspective between 2013-2020.<br><br>STUDY DESIGN: Sanger sequencing was performed on all samples with a positive enterovirus RT-qPCR result (&#x2264;Ct 32). Viral targeted sequence capture (ViroCap) and next-generation sequencing (NGS) (Illumina NextSeq 500) was used to characterize and generate near-complete CVA22 genomes for enteroviruses without genotyping results from Sanger sequencing. Epidemiological and phylogenetic analysis was performed using maximum likelihood trees on MEGA-11.<br><br>RESULTS: A total of twenty detections derived from fecal material from sixteen patients were observed between 2013- 2020. One transplant recipient had five different CVA22 infection episodes over five years, with phylogenetic analysis indicating possible reinfection with an additional prolonged infection (>3 weeks). Furthermore, we report the first two near-complete CVA22 sequences from Europe, which grouped with a strain previously isolated from Bangladesh in 1999.<br><br>CONCLUSIONS: We show a highly diverse enterovirus genotype which causes infections annually, typically in autumn and winter, and is capable of recurrent infection in an immunocompromised patient. Furthermore, we highlight the use of NGS to complement conventional targeted Sanger sequencing.}, }
@article {pmid36088469, year = {2022}, author = {Ju, Z and Guo, P and Xiang, J and Lei, R and Ren, G and Zhou, M and Yang, X and Zhou, P and Huang, R}, title = {Low-dose radiation exaggerates HFD-induced metabolic dysfunction by gut microbiota through PA-PYCR1 axis.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {945}, pmid = {36088469}, issn = {2399-3642}, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; *Insulin Resistance ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-akt ; }, abstract = {Co-exposure of High-fat-diet (HFD) behavior and environmental low-dose radiation (LDR) is common among majority occupational workers, but the synergism of this co-exposure in metabolic health is poorly understood. This study aimed to investigate the impact of gut microbiota and its metabolites on the regulation of HFD accompanied by LDR-associated with metabolic dysfunction and insulin resistance. Here, we reported that Parasutterella was markedly elevated in the gut microbiota of mice in co-exposure of HFD and LDR, accompanied by increased pyrrolidinecarboxylic acid (PA) level in both intestine and plasma. Transplantation of fecal microbiota from mice with co-exposure HFD and LDR with metabolic dysfunction resulted in increased disruption of metabolic dysfunction, insulin resistance and increased PYCR1 (Pyrroline-5-carboxylate reductase 1) expression. Mechanistically, intestinal barrier was damaged more serious in mice with co-exposure of HFD and LDR, leading high PA level in plasma, activating PYCR1 expression to inhibit insulin Akt/mTOR (AKT kinase-transforming protein/Serine threonine-protein kinase) signaling pathway to aggravate HFD-induced metabolic impairments. This study suggests a new avenue for interventions against western diet companied with low dose radiation exposure-driven metabolic impairments.}, }
@article {pmid36088134, year = {2023}, author = {Zhou, X and Xu, X and Lu, D and Chen, K and Wu, Y and Yang, X and Xiong, W and Chen, X and Lan, L and Li, W and Shen, S and He, W and Feng, X}, title = {Repeated early-life exposure to anaesthesia and surgery causes subsequent anxiety-like behaviour and gut microbiota dysbiosis in juvenile rats.}, journal = {British journal of anaesthesia}, volume = {130}, number = {2}, pages = {191-201}, pmid = {36088134}, issn = {1471-6771}, support = {RF1 AG070141/AG/NIA NIH HHS/United States ; }, mesh = {Rats ; Animals ; *Gastrointestinal Microbiome ; Serotonin/metabolism ; Hydroxyindoleacetic Acid ; Rats, Sprague-Dawley ; Dysbiosis/chemically induced ; Anxiety/etiology ; *Anesthesia ; }, abstract = {BACKGROUND: Early exposure to general anaesthetics for multiple surgeries or procedures might negatively affect brain development. Recent studies indicate the importance of microbiota in the development of stress-related behaviours. We determined whether repeated anaesthesia and surgery in early life cause gut microbiota dysbiosis and anxiety-like behaviours in rats.<br><br>METHODS: Sprague Dawley rats received skin incisions under sevoflurane 2.3 vol% three times during the first week of life. After 4 weeks, gut microbiota, anxiety-related behaviours, hippocampal serotonergic activity, and plasma stress hormones were tested. Subsequently, we explored the effect of faecal microbiota transplantation from multiple anaesthesia/surgery exposed rats after administration of a cocktail of antibiotics on anxiety-related behaviours.<br><br>RESULTS: Anxiety-like behaviours were observed in rats with repeated anaesthesia/surgery exposures: In the OF test, multiple anaesthesia/surgery exposures induced a decrease in the time spent in the centre compared to the Control group (P<0.05, t=3.05, df=16, Cohen's d=1.44, effect size=0.58). In the EPM test, rats in Multiple AS group travelled less (P<0.05, t=5.09, df=16, Cohen's d=2.40, effective size=0.77) and spent less time (P<0.05, t=3.58, df=16, Cohen's d=1.69, effect size=0.65) in the open arms when compared to the Control group. Repeated exposure caused severe gut microbiota dysbiosis, with exaggerated stress response (P<0.01, t=4.048, df=16, Cohen's d=-1.91, effect size=-0.69), a significant increase in the hippocampal concentration of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) (P<0.05; for 5-HT: t=3.33, df=18, Cohen's d=-1.49, effect size=-0.60; for 5-HIAA: t=3.12, df=18, Cohen's d=-1.40, effect size=-0.57), and changes in gene expression of serotonergic receptors later in life (for Htr1a: P<0.001, t=4.49, df=16, Cohen's d=2.24, effect size=0.75; for Htr2c: P<0.01, t=3.72, df=16, Cohen's d=1.86, effect size=0.68; for Htr6: P<0.001, t=7.76, df=16, Cohen's d=3.88, effect size=0.89). Faecal microbiota transplantation led to similar anxiety-like behaviours and changes in the levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid.<br><br>CONCLUSIONS: Gut microbiota dysbiosis caused by early repeated exposure to anaesthesia and surgery affects long-term anxiety emotion behaviours in rats.}, }
@article {pmid36085529, year = {2022}, author = {Xu, Q and Zhang, S and Quan, J and Wu, Z and Gu, S and Chen, Y and Zheng, B and Lv, L and Li, L}, title = {The evaluation of fecal microbiota transplantation vs vancomycin in a Clostridioides difficile infection model.}, journal = {Applied microbiology and biotechnology}, volume = {106}, number = {19-20}, pages = {6689-6700}, pmid = {36085529}, issn = {1432-0614}, mesh = {Animals ; *Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Granulocyte Colony-Stimulating Factor ; Inflammation Mediators ; Interleukin-6 ; Mice ; Raffinose ; Recurrence ; Treatment Outcome ; Tryptophan ; Tumor Necrosis Factor-alpha ; Valine ; Vancomycin/therapeutic use ; }, abstract = {Vancomycin is the preferred treatment for Clostridioides difficile infection (CDI) but has been associated with a high recurrence rate of CDI in treated patients. Fecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent CDI (rCDI). Herein, we present a mouse model of CDI to further define the changes in intestinal inflammation, flora, and metabolites following FMT versus vancomycin treatment and to find the potential therapy to restore colonization resistance. Both FMT and vancomycin treatment could ameliorate CDI-induced clinical features and intestinal tissue damage, with decrease in the levels of inflammatory mediators like IL-1β, IL-6, TNF-α, G-CSF, and MCP-1 in the colon and plasma. Observing the fecal gut microbiome profile revealed that unlike vancomycin, FMT could replenish intestinal microbiota by augmenting the relative abundance of the phylum Bacteroidetes and eliminating the abundance of the phylum Proteobacteria. FMT also reduced the levels of several carbohydrates, such as raffinose and fructose-6-phosphate, and amino acids, including tryptophan and glutamyl-valine, in the gut metabolome, thus suppressing C. difficile germination and growth. Our results suggest that the FMT-induced reconstruction of a specific gut community structure and restoration of metabolites promote the recovery of colonization resistance in mice better than vancomycin, thus offering new insights for the prevention of rCDI. KEY POINTS: • Both FMT and vancomycin ameliorate CDI-induced inflammatory response. • FMT restores a specific community structure and gut metabolites. • Mice treated with FMT may promote the recovery of colonization resistance and has a better outcome.}, }
@article {pmid36084869, year = {2022}, author = {Shi, C and Zhou, L and Li, H and Shi, X and Zhang, Y and Lu, Y and Zhu, H and Chen, D}, title = {Intestinal microbiota metabolizing Houttuynia cordata polysaccharides in H1N1 induced pneumonia mice contributed to Th17/Treg rebalance in gut-lung axis.}, journal = {International journal of biological macromolecules}, volume = {221}, number = {}, pages = {288-302}, doi = {10.1016/j.ijbiomac.2022.09.015}, pmid = {36084869}, issn = {1879-0003}, mesh = {Mice ; Animals ; *Houttuynia ; *Gastrointestinal Microbiome ; *Influenza A Virus, H1N1 Subtype ; T-Lymphocytes, Regulatory ; Lung ; *Pneumonia/drug therapy/metabolism/pathology ; Polysaccharides/therapeutic use ; }, abstract = {Influenza A virus is intricately linked to dysregulation of gut microbiota and host immunity. Previous study revealed that Houttuynia cordata polysaccharides (HCP) exert the therapeutic effect on influenza A virus inducing lung and intestine damage via regulating pulmonary and intestinal mucosal immunity. However, whether this result was due to the regulation of gut microbiota in the gut-lung axis remains unclear. Here, we firstly found that the elimination of gut microbiota using antibiotic cocktails led to both loss of the protective effect of HCP on intestine and lung injury, and reduction of the efficacy on regulating Th17/Treg balance in gut-lung axis. Fecal microbiota transplantation study confirmed that the gut microbiota fermented with HCP under pathological conditions (H1N1 infection) was responsible for reducing pulmonary and intestinal injury. Moreover, the interaction of HCP and gut microbiota under pathological conditions exhibited not only much more abundant gut microbial diversity, but also higher content of the acetate. Our results demonstrated that the underlying mechanism to ameliorate viral pneumonia in mice involving Th17/Treg rebalance via the gut microbiota and HCP metabolite (acetate) metabolized in pneumonia mice. Our results provided a new insight for macromolecular polysaccharides through targeting intestinal microenvironment reducing distant pulmonary infection.}, }
@article {pmid36084774, year = {2023}, author = {Luo, Y and Wang, J and Wang, C and Wang, D and Li, C and Zhang, B and Zhong, X and Chen, L and Li, H and Su, H and Zheng, Q and Zhu, D and Tang, H and Guo, L}, title = {The fecal arsenic excretion, tissue arsenic accumulation, and metabolomics analysis in sub-chronic arsenic-exposed mice after in situ arsenic-induced fecal microbiota transplantation.}, journal = {The Science of the total environment}, volume = {854}, number = {}, pages = {158583}, doi = {10.1016/j.scitotenv.2022.158583}, pmid = {36084774}, issn = {1879-1026}, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation ; *Arsenic/toxicity ; RNA, Ribosomal, 16S/genetics ; *Arsenic Poisoning ; Feces ; }, abstract = {Arsenic can be specifically enriched by rice, and the health hazards caused by high arsenic rice are gradually attracting attention. This study aimed to explore the potential of microbial detoxification via gut microbiome in the treatment of sub-chronic arsenic poisoning. We first exposed mice to high-dose arsenic feed (30 mg/kg, rice arsenic composition) for 60 days to promote arsenic-induced microbes in situ in the gastrointestinal tract, then transplanted their fecal microbiota (FMT) into another batch of healthy recipient mice, and dynamically monitored the microbial colonization by 16S rRNA sequencing and ITS sequencing. The results showed that in situ arsenic-induced fecal microbiome can stably colonized and interact with indigenous microbes in the recipient mice in two weeks, and established a more stable network of gut microbiome. Then, the recipient mice continued to receive high-dose arsenic exposure for 52 days. After above sub-chronic arsenic exposure, compared with the non-FMT group, fecal arsenic excretion, liver and plasma arsenic accumulation were significantly lower (P < 0.05), and that in kidney, hair, and thighbone present no significant differences. Metabolomics of feces- plasma-brain axis were also disturbed, some up-regulated metabolites in feces, plasma, and cerebral cortex may play positive roles for the host. Therefore, microbial detoxification has potential in the treatment of sub-chronic arsenic poisoning. However, gut flora is an extremely complex community with different microorganisms have different arsenic metabolizing abilities, and various microbial metabolites. Coupled with the matrix effects, these factors will have various effects on the efflux and accumulation of arsenic. The definite effects (detoxification or non-detoxification) could be not assured based on the current study, and more systematic and rigorous studies are needed in the future.}, }
@article {pmid36084771, year = {2022}, author = {Kong, B and Fu, H and Xiao, Z and Zhou, Y and Shuai, W and Huang, H}, title = {Gut Microbiota Dysbiosis Induced by a High-Fat Diet Increases Susceptibility to Atrial Fibrillation.}, journal = {The Canadian journal of cardiology}, volume = {38}, number = {12}, pages = {1962-1975}, doi = {10.1016/j.cjca.2022.08.231}, pmid = {36084771}, issn = {1916-7075}, mesh = {Mice ; Animals ; *Diet, High-Fat/adverse effects ; *Atrial Fibrillation/etiology ; RNA, Ribosomal, 16S ; NF-kappa B ; Dysbiosis/complications/metabolism ; Obesity ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Obesity is a significant risk factor for atrial fibrillation (AF), and the gut microbiota is closely related to obesity-induced diseases. However, whether the gut microbiota is involved in regulating obesity-induced AF has not been studied. This study investigated whether gut microbiota dysbiosis affects obesity-related AF.<br><br>METHODS: Fecal microbes derived from normal diet (ND)-fed and high-fat diet (HD)-fed mice were transplanted into those fed normally. Morphologic, biochemical, functional, histologic, electrophysiological studies, molecular analysis, 16S rRNA gene amplicon sequencing, and RNA-sequencing were performed.<br><br>RESULTS: Transplantation of the HD gut microbes in ND-maintained (THD) mice led to a significant increase in the susceptibility to AF. Gut microbiota analysis showed a significant increase in Desulfovibrionaceae, which generated metabolic endotoxemia in THD mice. Transplantation with HD microbes also resulted in significantly increased levels of circulating lipopolysaccharide (LPS), significant disruption in the histologic architecture of the intestinal tissue, and significantly increased proinflammatory cytokines in the left atrium, indicating that atrial inflammation likely contributed to AF susceptibility. RNA-sequencing showed that the THD group had enhanced activation of ferroptosis and TLR4/NF-&#x3ba;B/NLRP3 inflammasome signalling pathway. Inhibiting the ferroptosis or NLRP3 inflammasome signalling pathway significantly improved atrial fibrosis and reduced susceptibility to obesity-related gut dysbiosis-induced AF.<br><br>CONCLUSIONS: This study provides evidence showing an original causal role of gut microbiota dysbiosis in the pathogenesis of obesity-related AF, which showed elevated LPS and dysregulation of atrial pathologic remodelling by activating ferroptosis and the TLR4/NF-&#x3ba;B/NLRP3 inflammasome signalling pathway.}, }
@article {pmid36079724, year = {2022}, author = {Zheng, Z and Wang, S and Wu, C and Cao, Y and Gu, Q and Zhu, Y and Zhang, W and Hu, W}, title = {Gut Microbiota Dysbiosis after Traumatic Brain Injury Contributes to Persistent Microglial Activation Associated with Upregulated Lyz2 and Shifted Tryptophan Metabolic Phenotype.}, journal = {Nutrients}, volume = {14}, number = {17}, pages = {}, pmid = {36079724}, issn = {2072-6643}, support = {OO20200485//Construction Fund of Medical Key Disciplines of Hangzhou/ ; }, mesh = {Animals ; *Brain Injuries, Traumatic/complications ; Dysbiosis/complications ; *Gastrointestinal Microbiome/physiology ; Humans ; Mice ; Mice, Inbred C57BL ; Microglia ; Phenotype ; RNA, Ribosomal, 16S/genetics/metabolism ; Tryptophan/metabolism ; }, abstract = {Traumatic brain injury (TBI) is a common cause of disability and mortality, affecting millions of people every year. The neuroinflammation and immune response post-TBI initially have neuroprotective and reparative effects, but prolonged neuroinflammation leads to secondary injury and increases the risk of chronic neurodegenerative diseases. Persistent microglial activation plays a critical role in chronic neuroinflammation post-TBI. Given the bidirectional communication along the brain-gut axis, it is plausible to suppose that gut microbiota dysbiosis post-TBI influences microglial activation. In the present study, hippocampal microglial activation was observed at 7 days and 28 days post-TBI. However, in TBI mice with a depletion of gut microbiota, microglia were activated at 7 days post-TBI, but not at 28 days post-TBI, indicating that gut microbiota contributes to the long-term activation of microglia post-TBI. In addition, in conventional mice colonized by the gut microbiota of TBI mice using fecal microbiota transplant (FMT), microglial activation was observed at 28 days post-TBI, but not at 7 days post-TBI, supporting the role of gut microbiota dysbiosis in persistent microglial activation post-TBI. The RNA sequencing of the hippocampus identified a microglial activation gene, Lyz2, which kept upregulation post-TBI. This persistent upregulation was inhibited by oral antibiotics and partly induced by FMT. 16s rRNA gene sequencing showed that the composition and function of gut microbiota shifted over time post-TBI with progressive dysbiosis, and untargeted metabolomics profiling revealed that the tryptophan metabolic phenotype was differently reshaped at 7 days and 28 days post-TBI, which may play a role in the persistent upregulation of Lyz2 and the activation of microglia. This study implicates that gut microbiota and Lyz2 are potential targets for the development of novel strategies to address persistent microglial activation and chronic neuroinflammation post-TBI, and further investigations are warranted to elucidate the specific mechanism.}, }
@article {pmid36078124, year = {2022}, author = {Lanthier, N and Delzenne, N}, title = {Targeting the Gut Microbiome to Treat Metabolic Dysfunction-Associated Fatty Liver Disease: Ready for Prime Time?.}, journal = {Cells}, volume = {11}, number = {17}, pages = {}, pmid = {36078124}, issn = {2073-4409}, mesh = {Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Non-alcoholic Fatty Liver Disease ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. Animal studies have also shown a causal role of gut microbiota in liver metabolic disorders including steatosis whereas the human situation is less clear. Patients with metabolic dysfunction associated fatty liver disease (MAFLD) also have a modification in their gut microbiota composition but the changes are not fully characterized. The absence of consensus on a precise signature is probably due to disease heterogeneity, possible concomitant medications and different selection or evaluation criteria. The most consistent changes were increased relative abundance of Proteobacteria, Enterobacteriaceae and Escherichia species and decreased abundance of Coprococcus and Eubacterium. Possible mechanisms linking the microbiota and MAFLD are increased intestinal permeability with translocation of microbial products into the portal circulation, but also changes in the bile acids and production of microbial metabolites such as ethanol, short chain fatty acids and amino acid derivatives able to modulate liver metabolism and inflammation. Several interventional studies exist that attempt to modulate liver disease by administering antibiotics, probiotics, prebiotics, synbiotics, postbiotics or fecal transplantation. In conclusion, there are both gaps and hopes concerning the interest of gut microbiome evaluation for diagnosis purposes of MAFLD and for new therapeutic developments that are often tested on small size cohorts.}, }
@article {pmid36077084, year = {2022}, author = {Hu, ML and Lian, WS and Wang, FS and Yang, CH and Huang, WT and Yang, JW and Chen, IY and Yang, MY}, title = {Presume Why Probiotics May Not Provide Protection in Inflammatory Bowel Disease through an Azoxymethane and Dextran Sodium Sulfate Murine Model.}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36077084}, issn = {1422-0067}, support = {CMRPG8K0861, CMRPG8K0862, CMRPG8K0863, CMRPD8H0011, CMRPD8J0011, CMRPD8J0012 and CMRPD8J0013//Chang Gung Memorial Hospital/ ; }, mesh = {Animals ; Azoxymethane/toxicity ; *Colitis/chemically induced/therapy ; *Colitis-Associated Neoplasms ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Dysbiosis/therapy ; *Inflammatory Bowel Diseases/therapy ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; *Probiotics/pharmacology ; Sulfates ; }, abstract = {Recent studies have shown dysbiosis is associated with inflammatory bowel disease (IBD). However, trying to restore microbial diversity via fecal microbiota transplantation (FMT) or probiotic intervention fails to achieve clinical benefit in IBD patients. We performed a probiotic intervention on a simulated IBD murine model to clarify their relationship. IBD was simulated by the protocol of azoxymethane and dextran sodium sulfate (AOM/DSS) to set up a colitis and colitis-associated neoplasm model on BALB/c mice. A single probiotic intervention using Clostridium butyricum Miyairi (CBM) on AOM/DSS mice to clarify the role of probiotic in colitis, colitis-associated neoplasm, gut microbiota, and immune cytokines was performed. We found dysbiosis occurred in AOM/DSS mice. The CBM intervention on AOM/DSS mice failed to improve colitis and colitis-associated neoplasms but changed microbial composition and unexpectedly increased expression of proinflammatory IL-17A in rectal tissue. We hypothesized that the probiotic intervention caused dysbiosis. To clarify the result, we performed inverse FMT using feces from AOM/DSS mice to normal recipients to validate the pathogenic effect of dysbiosis from AOM/DSS mice and found mice on inverse FMT did develop colitis and colon neoplasms. We presumed the probiotic intervention to some extent caused dysbiosis as inverse FMT. The role of probiotics in IBD requires further elucidation.}, }
@article {pmid36077063, year = {2022}, author = {D'Antonio, DL and Marchetti, S and Pignatelli, P and Piattelli, A and Curia, MC}, title = {The Oncobiome in Gastroenteric and Genitourinary Cancers.}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36077063}, issn = {1422-0067}, mesh = {Bacteria ; Dysbiosis/microbiology ; Female ; *Genital Neoplasms, Female ; Humans ; Male ; *Microbiota/physiology ; Quality of Life ; Tumor Microenvironment ; *Urogenital Neoplasms ; Vagina/microbiology ; }, abstract = {Early evidence suggests a strong association of microorganisms with several human cancers, and great efforts have been made to understand the pathophysiology underlying microbial carcinogenesis. Bacterial dysbiosis causes epithelial barrier failure, immune dysregulation and/or genotoxicity and, consequently, creates a tumor-permissive microenvironment. The majority of the bacteria in our body reside in the gastrointestinal tract, known as gut microbiota, which represents a complex and delicate ecosystem. Gut microbes can reach the pancreas, stomach and colon via the bloodstream. Oral bacterial translocations can also occur. In the stomach, pancreas and colon, low microbial diversity is associated with cancer, in particular with a bad prognosis. The urogenital tract also harbors unique microbiota, distinct from the gut microbiota, which might have a role in the urinary and female/male reproductive cancers' pathogenesis. In healthy women, the majority of bacteria reside in the vagina and cervix and unlike other mucosal sites, the vaginal microbiota exhibits low microbial diversity. Genital dysbiosis might have an active role in the development and/or progression of gynecological malignancies through mechanisms including modulation of oestrogen metabolism. Urinary dysbiosis may influence the pathogenesis of bladder cancer and prostate cancer in males. Modulation of the microbiome via pre, pro and postbiotics, fecal or vaginal microbiota transplantation and engineering bacteria might prove useful in improving cancer treatment response and quality of life. Elucidating the complex host-microbiome interactions will result in prevention and therapeutic efficacy interventions.}, }
@article {pmid36075210, year = {2022}, author = {Cheng, J and Zhang, X and Zhang, D and Zhang, Y and Li, X and Zhao, Y and Xu, D and Zhao, L and Li, W and Wang, J and Zhou, B and Lin, C and Yang, X and Zhai, R and Cui, P and Zeng, X and Huang, Y and Ma, Z and Liu, J and Wang, W}, title = {Sheep fecal transplantation affects growth performance in mouse models by altering gut microbiota.}, journal = {Journal of animal science}, volume = {100}, number = {11}, pages = {}, pmid = {36075210}, issn = {1525-3163}, support = {2021YFD1300901//National Key R&amp;D Program of China/ ; 20YF3NA012//Key R&amp;D Program of Gansu Province/ ; //Chinese Academy of Sciences/ ; //Western Young Scholars/ ; }, mesh = {Mice ; Sheep ; Animals ; *Fecal Microbiota Transplantation/veterinary/methods ; *Gastrointestinal Microbiome ; Feces/microbiology ; Gastrointestinal Tract/microbiology ; Bacteria ; }, abstract = {Animal growth traits are important and complex traits that determine the productivity of animal husbandry. There are many factors that affect growth traits, among which diet digestion is the key factor. In the process of animal digestion and absorption, the role of gastrointestinal microbes is essential. In this study, we transplanted two groups of sheep intestinal microorganisms with different body weights into the intestines of mice of the same age to observe the effect of fecal bacteria transplantation on the growth characteristics of the mouse model. The results showed that receiving fecal microbiota transplantation (FMT) had an effect on the growth traits of recipient mice (P < 0.05). Interestingly, only mice receiving high-weight donor microorganisms showed differences. Use 16S rDNA sequencing technology to analyze the stool microorganisms of sheep and mice. The microbial analysis of mouse feces showed that receiving FMT could improve the diversity and richness of microorganisms (P < 0.05), and the microbial composition of mouse feces receiving low-weight donor microorganisms was similar to that of the control group, which was consistent with the change trend of growth traits. The feces of high-weight sheep may have higher colonization ability. The same five biomarkers were identified in the donor and recipient, all belonging to Firmicutes, and were positively correlated with the body weight of mice at each stage. These results suggest that FMT affects the growth traits of receptors by remodeling their gut microflora.}, }
@article {pmid36073800, year = {2022}, author = {Michael, H and Srivastava, V and Deblais, L and Amimo, JO and Chepngeno, J and Saif, LJ and Rajashekara, G and Vlasova, AN}, title = {The Combined Escherichia coli Nissle 1917 and Tryptophan Treatment Modulates Immune and Metabolome Responses to Human Rotavirus Infection in a Human Infant Fecal Microbiota-Transplanted Malnourished Gnotobiotic Pig Model.}, journal = {mSphere}, volume = {7}, number = {5}, pages = {e0027022}, pmid = {36073800}, issn = {2379-5042}, support = {R01 HD095881/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Humans ; Infant ; Aminobenzoates ; Biliverdine/metabolism ; Cholesterol ; Coenzyme A/metabolism ; Coproporphyrinogens ; Cytidine/metabolism ; Diarrhea ; Escherichia coli/metabolism ; *Escherichia coli Infections ; *Fecal Microbiota Transplantation ; Germ-Free Life ; Inosine/metabolism ; Lipids ; *Malnutrition/therapy/complications ; Metabolome ; Microbiota ; Nucleotides/metabolism ; Phenylalanine/metabolism ; Rotavirus ; *Rotavirus Infections ; Sulfates ; Swine ; *Tryptophan/pharmacology ; Urobilinogen/metabolism ; Xanthines ; }, abstract = {Human rotavirus (HRV) is a major cause of childhood diarrhea in developing countries where widespread malnutrition contributes to the decreased oral vaccine efficacy and increased prevalence of other enteric infections, which are major concerns for global health. Neonatal gnotobiotic (Gn) piglets closely resemble human infants in their anatomy, physiology, and outbred status, providing a unique model to investigate malnutrition, supplementations, and HRV infection. To understand the molecular signatures associated with immune enhancement and reduced diarrheal severity by Escherichia coli Nissle 1917 (EcN) and tryptophan (TRP), immunological responses and global nontargeted metabolomics and lipidomics approaches were investigated on the plasma and fecal contents of malnourished pigs transplanted with human infant fecal microbiota and infected with virulent (Vir) HRV. Overall, EcN + TRP combined (rather than individual supplement action) promoted greater and balanced immunoregulatory/immunostimulatory responses associated with greater protection against HRV infection and disease in malnourished humanized piglets. Moreover, EcN + TRP treatment upregulated the production of several metabolites with immunoregulatory/immunostimulatory properties: amino acids (N-acetylserotonin, methylacetoacetyl-CoA), lipids (gamma-butyrobetaine, eicosanoids, cholesterol-sulfate, sphinganine/phytosphingosine, leukotriene), organic compound (biliverdin), benzenoids (gentisic acid, aminobenzoic acid), and nucleotides (hypoxathine/inosine/xanthine, cytidine-5'-monophosphate). Additionally, the levels of several proinflammatory metabolites of organic compounds (adenosylhomocysteine, phenylacetylglycine, urobilinogen/coproporphyrinogen) and amino acid (phenylalanine) were reduced following EcN + TRP treatment. These results suggest that the EcN + TRP effects on reducing HRV diarrhea in neonatal Gn pigs were at least in part due to altered metabolites, those involved in lipid, amino acid, benzenoids, organic compounds, and nucleotide metabolism. Identification of these important mechanisms of EcN/TRP prevention of HRV diarrhea provides novel targets for therapeutics development. IMPORTANCE Human rotavirus (HRV) is the most common cause of viral gastroenteritis in children, especially in developing countries, where the efficacy of oral HRV vaccines is reduced. Escherichia coli Nissle 1917 (EcN) is used to treat enteric infections and ulcerative colitis while tryptophan (TRP) is a biomarker of malnutrition, and its supplementation can alleviate intestinal inflammation and normalize intestinal microbiota in malnourished hosts. Supplementation of EcN + TRP to malnourished humanized gnotobiotic piglets enhanced immune responses and resulted in greater protection against HRV infection and diarrhea. Moreover, EcN + TRP supplementation increased the levels of immunoregulatory/immunostimulatory metabolites while decreasing the production of proinflammatory metabolites in plasma and fecal samples. Profiling of immunoregulatory and proinflammatory biomarkers associated with HRV perturbations will aid in the identification of treatments against HRV and other enteric diseases in malnourished children.}, }
@article {pmid36071979, year = {2022}, author = {Piazzesi, A and Putignani, L}, title = {Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {958346}, pmid = {36071979}, issn = {1664-302X}, abstract = {Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.}, }
@article {pmid36071974, year = {2022}, author = {Liu, JY and Lin, TL and Chiu, CY and Hsieh, PF and Lin, YT and Lai, LY and Wang, JT}, title = {Decolonization of carbapenem-resistant Klebsiella pneumoniae from the intestinal microbiota of model mice by phages targeting two surface structures.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {877074}, pmid = {36071974}, issn = {1664-302X}, abstract = {BACKGROUND: Klebsiella pneumoniae is a normal component of the human gastrointestinal tract microbiota. However, in some cases, it can cause disease. Over the past 20 years, the prevalence of antibiotic-resistant bacteria, such as carbapenem-resistant K. pneumoniae (CRKP), has been increasing.<br><br>MATERIALS AND METHODS: We attempted to specifically eliminate CRKP from a mouse model with the human intestinal microbiota. To establish humanized microbiota-colonized mice, we administered K64 CRKP-containing human microbiota to germ-free mice by fecal microbiota transplantation. Then, we used two phages, one targeting the capsule (&#x3c6;K64-1) and one targeting O1 lipopolysaccharide (&#x3c6;KO1-1) of K64 K. pneumoniae, to eliminate CRKP.<br><br>RESULTS: In untreated control and &#x3c6;KO1-1-treated K64-colonized mice, no change in CRKP was observed, while in mice treated with &#x3c6;K64-1, a transient reduction was observed. In half of the mice treated with both &#x3c6;KO1-1 and &#x3c6;K64-1, CRKP was undetectable in feces by PCR and culture for 60 days. However, in the other 50% of the mice, K. pneumoniae was transiently reduced but recovered 35 days after treatment.<br><br>CONCLUSION: Combination treatment with &#x3c6;K64-1 and &#x3c6;KO1-1 achieved long-term decolonization in 52.3% of mice carrying CRKP. Importantly, the composition of the intestinal microbiota was not altered after phage treatment. Therefore, this strategy may be useful not only for eradicating drug-resistant bacterial species from the intestinal microbiota but also for the treatment of other dysbiosis-associated diseases.}, }
@article {pmid36066910, year = {2022}, author = {Wang, JG and Liang, Q and Dou, HH and Ou, Y}, title = {The global incidence of adverse events associated with fecal microbiota transplantation in children over the past 20 years: A systematic review and meta-analysis.}, journal = {Journal of gastroenterology and hepatology}, volume = {37}, number = {11}, pages = {2031-2038}, doi = {10.1111/jgh.15996}, pmid = {36066910}, issn = {1440-1746}, mesh = {Child ; Humans ; Fecal Microbiota Transplantation/adverse effects ; Incidence ; *Clostridium Infections/etiology ; *Enterocolitis, Pseudomembranous ; Gastrointestinal Hemorrhage/etiology ; Treatment Outcome ; }, abstract = {OBJECTIVES: To understand the global incidence of the adverse events associated with fecal microbiota transplantation (FMT) in children over the past 20 years.<br><br>METHODS: We searched PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and Chongqing Weipu) for high-quality articles written over the past 20&#xa0;years and made selections based on the quality standard score. The study characteristics and incidences of adverse events were extracted from each article, meta-analysis was performed using the R.3.6.3 software, and randomized-effect or fixed-effect meta-analyses were used to determine the incidence of adverse events. Subgroup analysis was performed to determine heterogeneity.<br><br>RESULTS: A total of 18 articles involving 681 children were included in the analysis. The total effective rate of FMT in children was 85.75% (95% CI: 76.23-93.15%), of which the overall efficacy of FMT for the treatment of Clostridium difficile infection was 91.22% (95% CI: 83.49-96.68%) and the overall adverse event rate was 28.86% (95% CI: 19.56-39.15%), with a mild to moderate adverse event rate of 27.72% (95% CI: 17.86-38.83%) and a severe adverse event rate of 0.90% (95% CI: 0.33-1.76%). The most common mild to moderate adverse events were as follows: bellyache, 14.02% (95% CI: 5.43-25.77%); diarrhea, 7.75% (95% CI: 2.69-15.11%); and bloating, 7.36% (95% CI: 1.79-16.28%). Other adverse events included fever, 2.34%; vomiting, 3.12%; nausea, 1.50%; hematochezia, 2.30%; anorexia, 1.94%; and fatigue, 0.03%. The only death reported was in a study from China, in which the patient died of sepsis and liver failure 4&#xa0;weeks after FMT. The other serious adverse event was an immunodeficiency patient with severe hematochezia. Another study in the United States described seven serious adverse events including one death that was not considered to be related to FMT; however, they did not describe the events in detail. There was no difference in the incidence of adverse events between the upper and lower gastrointestinal tracts (OR&#xa0;=&#xa0;0.61, 95% CI: 0.02-15.42, P&#xa0;=&#xa0;0.76).<br><br>CONCLUSION: Adverse events related to FMT in children are mostly mild to moderate, of short duration, and self-limiting. Therefore, the use of FMT in children is safe and worthy of widespread promotion.}, }
@article {pmid36066591, year = {2022}, author = {Kelm, M and Reibetanz, J}, title = {[47/m patient with red blood depositions in feces : Preparation for the medical specialist examination: part 3].}, journal = {Chirurgie (Heidelberg, Germany)}, volume = {93}, number = {Suppl 1}, pages = {12-15}, doi = {10.1007/s00104-022-01711-x}, pmid = {36066591}, issn = {2731-698X}, mesh = {Humans ; Feces ; *Medicine ; }, }
@article {pmid36060783, year = {2022}, author = {Wang, M and Xie, X and Zhao, S and Han, W and Zhang, Y}, title = {Global research trends and hotspots of fecal microbiota transplantation: A bibliometric and visualization study.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {990800}, pmid = {36060783}, issn = {1664-302X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) has gained considerable attention in a variety of clinical research areas, and an increasing number of articles are being published. It is very critical to reveal the global status, future research trends, and hotspots in the FMT research and application.<br><br>METHODS: We searched the Web of Science Core Collection up to May 10, 2022, and only articles and review articles about FMT were included finally. CiteSpace 5.8.R3, VOSviewer 1.6.18, Scimago Graphica and Microsoft Office Excel 2019 were used for data analysis and visualization. The results included publication characteristics, Co-authorships analysis, Co-cited analysis, Co-occurrence analysis, and burst analysis.<br><br>RESULTS: Eleven thousand nine hundred seventy-two records were used for the analysis and visualization finally, these records were published between 1980 and 2022, and the publication about FMT is increasing year by year. Co-authorship analysis shown that the USA played a key role in this field. After data analysis and visualization, a total of 57 hotspots about FMT were produced. We summarized these hotspots and classified them into 7 grades according to the number of evidence sources. The evidence sources included top 25 of Web of Science categories, top 30 most Co-cited references, top 10 clusters of references, top 25 references with the strongest citation bursts, top 25 keywords with the most occurrence frequency, major 15 clusters of keywords, top 25 keywords with the strongest citation bursts, and top 35 disease keywords.<br><br>CONCLUSION: This bibliometric analysis is expected to provide overall perspective for FMT. FMT has gained increasing attention and interest, there are many hotspots in this field, which may help researchers to explore new directions for future research.}, }
@article {pmid36058787, year = {2022}, author = {Lythgoe, MP and Mullish, BH and Frampton, AE and Krell, J}, title = {Polymorphic microbes: a new emerging hallmark of cancer.}, journal = {Trends in microbiology}, volume = {30}, number = {12}, pages = {1131-1134}, doi = {10.1016/j.tim.2022.08.004}, pmid = {36058787}, issn = {1878-4380}, support = {CL-2019-21-002/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota ; *Neoplasms ; }, abstract = {Recognition of the microbiome (and 'polymorphic microbes' within them) as a new emerging hallmark of cancer reflects a wide body of rapidly evolving research. Microbes may be directly carcinogenic, impact host immune responses to promote malignancy, and may be key effectors in determining the efficacy of anticancer therapy. Manipulation of the microbiome is showing promise as an opportunity to influence cancer outcomes.}, }
@article {pmid36058152, year = {2022}, author = {Bai, J and Cai, Y and Huang, Z and Gu, Y and Huang, N and Sun, R and Zhang, G and Liu, R}, title = {Shouhui Tongbian Capsule ameliorates constipation via gut microbiota-5-HT-intestinal motility axis.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {154}, number = {}, pages = {113627}, doi = {10.1016/j.biopha.2022.113627}, pmid = {36058152}, issn = {1950-6007}, mesh = {Animals ; Constipation/chemically induced/drug therapy ; Dysbiosis ; *Gastrointestinal Microbiome ; Gastrointestinal Motility/physiology ; Loperamide/therapeutic use ; Mice ; Serotonin/metabolism ; }, abstract = {Constipation has become an epidemic enteric medical problem, accompanied with increasing long-term sequelae. Gut microbiota and serotonin (5-HT) have been believed as predominant player in the treatment of constipation. In clinical practices, Shouhui Tongbian Capsule (SHTB) was found to effectively improve constipation symptoms and promote gastrointestinal motility. However, the specific mechanism of SHTB is not clearly elucidated. Our current study aims to explore the therapeutic effects of SHTB against the development of constipation and the underlying mechanisms related to gut bacterial and 5-HT. We established loperamide hydrochloride (LH)-induced experimental constipation mouse model to evaluate the effect of SHTB. 16S RNA sequencing, fecal microbiota transplants (FMT), high performance liquid chromatograph, and molecular biological analysis were performed to investigate the potential mechanisms of SHTB. Our data demonstrated that SHTB significantly ameliorated LH-induced experimental constipation and accelerated enteric motility via promoting 5-HT biosynthesis in enterochromaffin cells and enteric neuron growth of the enteric nervous system (ENS) in both the small intestine and colon. Additionally, SHTB significantly modulated gut microbiota dysbiosis and potentially altered microbiota metabolites to enhance intestinal 5-HT production. Finally, FMT study confirmed that the effects of SHTB on 5-HT production and constipation are dependent on modulating intestinal microbiota dysbiosis. In conclusion, our current study deciphered therapeutic mechanism of SHTB in the treatment of experimental constipation from perspectives of gut microbiota-5-HT-intetinal motility axis and provides novel insights into the appropriate and safe application of SHTB in the clinic.}, }
@article {pmid36056999, year = {2023}, author = {Fabian, O and Klocperk, A and Lerchova, T and Jencova, P and Stolova, L and Belhajova, M and Voriskova, D and Kazeka, D and Vicha, A and Hradsky, O and Bronsky, J}, title = {Serum and Mucosal CD30 in Pediatric Inflammatory Bowel Diseases: Useful Biomarker for Diagnosis and Disease Activity Monitoring?.}, journal = {Digestive diseases and sciences}, volume = {68}, number = {2}, pages = {460-470}, pmid = {36056999}, issn = {1573-2568}, mesh = {Humans ; Child ; Tumor Necrosis Factor Inhibitors ; *Inflammatory Bowel Diseases/complications ; *Colitis, Ulcerative/diagnosis ; *Crohn Disease/diagnosis ; Biomarkers/analysis ; T-Lymphocyte Subsets ; Intestinal Mucosa/pathology ; Inflammation/pathology ; }, abstract = {BACKGROUND: Inflammatory bowel diseases (IBD) frequently manifest in pediatric age, but may have atypical clinical, histological and laboratory features. Their underlying immune pathophysiology is incompletely understood, rendering quick diagnosis followed by tailored therapy difficult. The tumor necrosis factor superfamily receptor CD30 has been proposed as a potential marker of ulcerative colitis (UC) and has also been associated with elevated Th2 helper T cells.<br><br>METHODS: A cohort of pediatric patients with UC and Crohn's disease (CD) was evaluated for serum soluble CD30 (sCD30) using ELISA and expression of CD30 and subpopulations of Th1/Th2/Th17 lymphocytes in the gastrointestinal mucosa using flow cytometry (FCM). The dataset is supported by endoscopic and microscopic activity of the disease and basic laboratory markers of inflammation.<br><br>RESULTS: The cohort consisted of 102 observations from 94 patients. sCD30 levels did not differ between patients with CD or UC. However, sCD30 levels correlated with levels of CRP, ESR, fecal calprotectin and albumin and also with clinical activity of the disease in patients with both UC and CD. FCM was not helpful in evaluation of mucosal CD30, which was lowly expressed and not associated with the diagnosis or disease activity. We show augmented Th2 and Th1/17 response in terminal ileum and right-sided colon and decreased Th1/17 response in left-sided colon of UC patients. T lymphocyte subsets were also affected by anti-TNF treatment and patients' age.<br><br>CONCLUSIONS: Neither sCD30 nor mucosal CD30 expression was helpful in differentiating between UC and CD. sCD30 seems to reflect a degree of systemic inflammation and clinical activity in IBD.}, }
@article {pmid36056902, year = {2023}, author = {Hole, MJ and Jørgensen, KK and Holm, K and Braadland, PR and Meyer-Myklestad, MH and Medhus, AW and Reikvam, DH and Götz, A and Grzyb, K and Boberg, KM and Karlsen, TH and Kummen, M and Hov, JR}, title = {A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation.}, journal = {Hepatology (Baltimore, Md.)}, volume = {77}, number = {3}, pages = {715-728}, pmid = {36056902}, issn = {1527-3350}, mesh = {Humans ; *Liver Transplantation ; *Cholangitis, Sclerosing/surgery/complications ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases ; Liver/pathology ; }, abstract = {BACKGROUND AND AIMS: Several characteristic features of the fecal microbiota have been described in primary sclerosing cholangitis (PSC), whereas data on mucosal microbiota are less consistent. We aimed to use a large colonoscopy cohort to investigate key knowledge gaps, including the role of gut microbiota in PSC with inflammatory bowel disease (IBD), the effect of liver transplantation (LT), and whether recurrent PSC (rPSC) may be used to define consistent microbiota features in PSC irrespective of LT.<br><br>APPROACH AND RESULTS: We included 84 PSC and 51 liver transplanted PSC patients (PSC-LT) and 40 healthy controls (HCs) and performed sequencing of the 16S ribosomal RNA gene (V3-V4) from ileocolonic biopsies. Intraindividual microbial diversity was reduced in both PSC and PSC-LT versus HCs. An expansion of Proteobacteria was more pronounced in PSC-LT (up to 19% relative abundance) than in PSC (up to 11%) and HCs (up to 8%; Q FDR &#x2009;<&#x2009;0.05). When investigating PSC before (PSC vs. HC) and after LT (rPSC vs. no-rPSC), increased variability (dispersion) in the PSC group was found. Five genera were associated with PSC before and after LT. A dysbiosis index calculated from the five genera, and the presence of the potential pathobiont, Klebsiella , were associated with reduced LT-free survival. Concomitant IBD was associated with reduced Akkermansia .<br><br>CONCLUSIONS: Consistent mucosal microbiota features associated with PSC, PSC-IBD, and disease severity, irrespective of LT status, highlight the usefulness of investigating PSC and rPSC in parallel, and suggest that the impact of gut microbiota on posttransplant liver health should be investigated further.}, }
@article {pmid36055123, year = {2022}, author = {Nandi, SK and Basu, S and Bhattacharjya, A and Dey Ghosh, R and Bose, CK and Mukhopadhyay, S and Bhattacharya, R}, title = {Interplay of gut microbiome, fatty acids, and the endocannabinoid system in regulating development, progression, immunomodulation, and chemoresistance of cancer.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {103-104}, number = {}, pages = {111787}, doi = {10.1016/j.nut.2022.111787}, pmid = {36055123}, issn = {1873-1244}, mesh = {Humans ; *Gastrointestinal Microbiome ; Endocannabinoids/pharmacology ; Fatty Acids/pharmacology ; Drug Resistance, Neoplasm ; Fatty Acids, Volatile/metabolism ; Immunomodulation ; Immunity ; *Fatty Acids, Omega-3/pharmacology ; *Neoplasms/drug therapy ; Tumor Microenvironment ; }, abstract = {The roles of gut microorganisms in cancer are diverse. Studies on metagenomics and bioinformatics have documented diverse microbial etiology in different tumors. Evidence supports that a commensal microbiome could provide a promising strategy to treat and prevent cancer through interference in several biologic processes, such as host cell survival and death, host immune function, inflammation, oncogenic signaling, and several hormone receptor signaling and detoxification pathways. The cumulative evidence recommends that metabolites of commensal gut microorganisms (e.g., short-chain fatty acids, omega-3 and -6 fatty acids) play an important role in cancer prevention, with a robust antiproliferative effect of omega-3 fatty acids. Intriguingly, the endocannabinoid system (omega-3 and -6 fatty acid-derived neurotransmitter of the body) shows diverse effects on cancer prevention and oncogenesis depending on the context of the tumor microenvironment. Thus, an interplay of gut microorganisms with their fatty acid metabolites and the endocannabinoid system play an important role in the development, progression, immunomodulation, and chemoresistance of cancer. In this review, we highlight aspects of the current knowledge of and interactions between the microbiome with fatty acids and the host endocannabinoid system. We also document their effect on host immunomodulation and chemoresistance, and discuss how these insights might translate into future development of microbiome-targeted therapeutic interventions.}, }
@article {pmid36054423, year = {2023}, author = {Wang, Q and Guo, X and Yue, Q and Zhu, S and Guo, L and Li, G and Zhou, Q and Xiang, Y and Chen, G and Yin, W and Sun, J}, title = {Exploring the role and mechanism of gut microbiota in methamphetamine addiction using antibiotic treatment followed by fecal microbiota transplantation.}, journal = {Anatomical record (Hoboken, N.J. : 2007)}, volume = {306}, number = {5}, pages = {1149-1164}, doi = {10.1002/ar.25055}, pmid = {36054423}, issn = {1932-8494}, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Mice, Inbred C57BL ; *Methamphetamine/pharmacology ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Recently, the role of the gut microbiota in the context of drug addiction has attracted the attention of researchers; however, the specific effects and underlying mechanisms require further exploration. To accomplish this, C57BL/6 mice were firstly treated with methamphetamine (MA). Conditioned place preference (CPP) behavior changes, gut permeability and function, microglial activation, and inflammatory cytokine expression were systematically analyzed in antibiotics-treated mice with microbiota depletion and in fecal microbiota transplantation mice with microbiota reconstitution. MA treatment altered microbiota composition and caused gut dysbiosis. Depletion of gut microbiota with antibiotics inhibited MA-induced CPP formation, and fecal microbiota transplantation reversed this inhibition. Mechanistic analyses indicated that antibiotic treatment decreased gut permeability and neuroinflammation, while fecal microbiota transplantation offset the impact of antibiotic treatment. Additionally, MA-induced microglial activation was suppressed by antibiotics but restored by microbiota transplantation, and this correlated well with the CPP score. Compared to antibiotic treatment, microbiota transplantation significantly increased 5-HT4 receptor expression in both the nucleus accumbens and the hippocampus. Furthermore, when fecal microbiota from healthy mice was transplanted into MA-treated mice, the CPP scores decreased. Our results provide a novel avenue for understanding MA addiction and suggest a potential future intervention strategy.}, }
@article {pmid36053300, year = {2022}, author = {Stallmach, A and Steube, A and Stallhofer, J and Grunert, PC and Merkel, U and Hartmann, M}, title = {[Fecal microbiota transplantation: indications, risks and opportunities].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {10}, pages = {1036-1042}, pmid = {36053300}, issn = {2731-7099}, mesh = {*COVID-19 ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation/adverse effects ; Humans ; SARS-CoV-2 ; }, abstract = {Fecal microbiome transfer (FMT) involving the transfer of the microbiome of healthy stool donors to patients with various diseases has been performed in Germany in clinical studies and individual treatment attempts. There is no doubt that FMT is an effective therapeutic principle for recurrent Clostridium difficile infection and ulcerative colitis. From a medico-legal point of view, it should be stressed that, in Germany, the microbiome to be transferred is regarded as a drug, the manufacture of which is subject to the Medicines Act and the risk information from the Federal Institute for Drugs and Medical Devices. The background of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the potential risk of transmitting pathogens must also be considered. There is an obligation to notify the competent state authorities to perform FMTs in the context of individual treatment attempts. In the context of the limited availability and the fundamental problem of infection, future studies aim to identify the therapeutically active components in the microbiome. Recombinant production is the aim. Initial results represent preliminary steps, as these concepts are not yet established in clinical practice.}, }
@article {pmid36051343, year = {2022}, author = {Alberca, GGF and Cardoso, NSS and Solis-Castro, RL and Nakano, V and Alberca, RW}, title = {Intestinal inflammation and the microbiota: Beyond diversity.}, journal = {World journal of gastroenterology}, volume = {28}, number = {26}, pages = {3274-3278}, pmid = {36051343}, issn = {2219-2840}, mesh = {*Colitis, Ulcerative/microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Intestinal Mucosa/microbiology ; *Microbiota ; }, abstract = {The recent manuscript entitled "Relationship between clinical features and intestinal microbiota in Chinese patients with ulcerative colitis" reported a difference in the intestinal microbiota of patients with ulcerative colitis according to the severity of the colitis. The influence of the intestinal microbiota on the development and progress of gastrointestinal disorders is well established. Besides the diversity in the microbiome, the presence of virulence factors and toxins by commensal bacteria may affect an extensive variety of cellular processes, contributing to the induction of a proinflammatory environment.}, }
@article {pmid36047142, year = {2022}, author = {Mukohda, M and Mizuno, R and Ozaki, H}, title = {[Gut microflora and metabolic syndrome: new insight into the pathogenesis of hypertension].}, journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica}, volume = {157}, number = {5}, pages = {311-315}, doi = {10.1254/fpj.22035}, pmid = {36047142}, issn = {0015-5691}, mesh = {Adult ; Animals ; Blood Pressure ; *Cardiovascular Diseases ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Hypertension/etiology/metabolism ; *Metabolic Diseases ; *Metabolic Syndrome/etiology ; Mice ; Rats ; Rats, Inbred SHR ; }, abstract = {Emerging evidences indicate that a microbial imbalance (dysbiosis) is linked to several diseases including metabolic cardiovascular diseases. A fecal microbiota transplantation from hypertensive human donor to germ-free mice caused blood pressure elevation. In addition, there is a report demonstrating that angiotensin II-induced hypertension and vascular dysfunction were attenuated in germ-free mice, suggesting that gut microbiome may mediate development of hypertension. Although detailed mechanism by which the dysbiosis induces an increased blood pressure remains unknown, changes in microbiome may modify host immune systems and induce inflammatory dysfunction in cardiovascular system, resulting in dysregulation of blood pressure. Some cohort studies demonstrated an association between a higher abundance of Streptococcaceae spp. and blood pressure. One recent report demonstrated that an increasing number of gram-positive Streptococcus was found in the feces of adult spontaneously hypertensive rats with an increased intestinal permeability. We hypothesized that increased bacterial toxin levels derived from gut Streptococcus may be a factor inducing blood pressure dysregulation. In this review, we discuss the possible role of microbiome in cardiovascular disease, especially hypertension.}, }
@article {pmid36045729, year = {2022}, author = {Chen, Y and Lian, B and Li, P and Yao, S and Hou, Z}, title = {Studies on irritable bowel syndrome associated with anxiety or depression in the last 20 years: A bibliometric analysis.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {947097}, pmid = {36045729}, issn = {2296-2565}, mesh = {Anxiety ; Bibliometrics ; Depression ; Humans ; *Irritable Bowel Syndrome ; Publications ; }, abstract = {Irritable bowel syndrome (IBS) associated with anxiety or depression is ubiquitous in clinical practice, and multiple related articles have been published. However, studies that utilize bibliometric analyses to address this topic are rare. In our study, we aimed to reveal research trends in IBS with anxiety or depression. Publications on IBS in relation to anxiety or depression in the last 20 years were obtained from the Web of Science Core Collection (WoSCC). CiteSpace software (5.8.R3) and GraphPad Prism 8 were used to perform bibliometric analysis of authors, countries, institutions, journals, keywords, and references involved in this topic. A total of 2,562 publications from 716 academic journals were included in this study. The majority of publications (n = 833, 32.51%) were from the USA, and the University of California, Los Angeles, contributed the most publications (n = 97, 3.79%). Active cooperations among countries and institutions were observed. Neurogastroenterology and Motility [impact factor (IF) 2020 = 3.598] published the most papers (170 publications, 6.64%), followed by Alimentary Pharmacology Therapeutics (IF 2020 = 8.171; 88 publications; 3.44%). The literatures related to IBS and anxiety or depression were primarily published in journals related to medicine/medical/clinical, neurology/sports/ophthalmology, and molecular/biology/immunology. Cryan JF and Drossman DA, with the largest number of articles (84 publications) and citations (917 citations), respectively, were considered as the most influential authors in this field. A total of 336 co-cited references were divided into 17 clusters, and #1 fecal microbiota transplantation contained most of the documents published in recent years. Moreover, the keyword "psychosocial factor" had the largest burst strength of 13.52, followed by the keyword "gut microbiota" with a burst strength of 11.71. This study shows the research performance of IBS related to anxiety or depression from 2002 to 2021 and helps researchers master the trend in this field, which should receive more attention.}, }
@article {pmid36045303, year = {2022}, author = {Harding, C and Larsen, BB and Gryseels, S and Otto, HW and Suazo, C and Kraberger, S and Upham, NS and Worobey, M and Van Doorslaer, K and Varsani, A}, title = {Discovery of three cycloviruses in fecal samples from silver-haired bats (Lasionycteris noctivagans) in Arizona (USA).}, journal = {Archives of virology}, volume = {167}, number = {12}, pages = {2771-2775}, pmid = {36045303}, issn = {1432-8798}, support = {CH//Barrett's Honors College - Arizona State University/ ; Startup funds//School of Life Sciences, Arizona State University/ ; }, mesh = {Animals ; *Circoviridae ; *Chiroptera ; Feces ; Arizona ; }, abstract = {Bats harbour a diverse array of viruses, some of which are zoonotic, and are one of the most speciose groups of mammals on earth. As part of an ongoing bat-associated viral diversity research project, we identified three cycloviruses (family Circoviridae) in fecal samples of silver-haired bats (Lasionycteris noctivagans) caught in Cave Creek Canyon of Arizona (USA). Two of the three identified genomes represent two new species in the genus Cyclovirus. Cycloviruses have been found in a wide range of environments and hosts; however, little is known about their biology. These new genomes of cycloviruses are the first from silver-haired bats, adding to the broader knowledge of cyclovirus diversity. With continuing studies, it is likely that additional viruses of the family Circoviridae will be identified in Arizona bat populations.}, }
@article {pmid36044996, year = {2022}, author = {Maaloum, M and Lo, CI and Ndongo, S and Meng, MM and Saile, R and Alibar, S and Raoult, D and Fournier, PE}, title = {Ottowia massiliensis sp. nov., a new bacterium isolated from a fresh, healthy human fecal sample.}, journal = {FEMS microbiology letters}, volume = {369}, number = {1}, pages = {}, doi = {10.1093/femsle/fnac086}, pmid = {36044996}, issn = {1574-6968}, mesh = {Base Composition ; Catalase/genetics ; DNA, Bacterial/genetics ; Feces/microbiology ; Humans ; Phylogeny ; *RNA, Ribosomal, 16S/genetics ; }, abstract = {The culturomics method enabled isolation of a new member of the Ottowia genus from the stool sample of a healthy volunteer. Strain Marseille-P4747T exhibited a 96.18% 16S rRNA sequence identity with Ottowia beijingensis strain GCS-AN-3 (NR_133803.1), the closest species with standing in nomenclature. It is a Gram-stain-negative, nonmotile, and aerobic bacterium. It does not possess catalase and oxidase activities. Its genome has a size of 2 830 447 bp and a G + C content of 63.5 mol%. Based on the phylogenic, phenotypic, and genomic analyses, we conclude that Ottowia massiliensis sp. nov. is a new species, represented by Marseille-P4747T (= CSUR P4747 = CECT 30348) as type strain.}, }
@article {pmid36044594, year = {2022}, author = {Swarte, JC and Li, Y and Hu, S and Björk, JR and Gacesa, R and Vich Vila, A and Douwes, RM and Collij, V and Kurilshikov, A and Post, A and Klaassen, MAY and Eisenga, MF and Gomes-Neto, AW and Kremer, D and Jansen, BH and Knobbe, TJ and Berger, SP and Sanders, JF and Heiner-Fokkema, MR and Porte, RJ and Cuperus, FJC and de Meijer, VE and Wijmenga, C and Festen, EAM and Zhernakova, A and Fu, J and Harmsen, HJM and Blokzijl, H and Bakker, SJL and Weersma, RK}, title = {Gut microbiome dysbiosis is associated with increased mortality after solid organ transplantation.}, journal = {Science translational medicine}, volume = {14}, number = {660}, pages = {eabn7566}, doi = {10.1126/scitranslmed.abn7566}, pmid = {36044594}, issn = {1946-6242}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome/genetics ; *Hematopoietic Stem Cell Transplantation ; Humans ; *Organ Transplantation ; Virulence Factors ; }, abstract = {Organ transplantation is a life-saving treatment for patients with end-stage disease, but survival rates after transplantation vary considerably. There is now increasing evidence that the gut microbiome is linked to the survival of patients undergoing hematopoietic cell transplant, yet little is known about the role of the gut microbiome in solid organ transplantation. We analyzed 1370 fecal samples from 415 liver and 672 renal transplant recipients using shotgun metagenomic sequencing to assess microbial taxonomy, metabolic pathways, antibiotic resistance genes, and virulence factors. To quantify taxonomic and metabolic dysbiosis, we also analyzed 1183 age-, sex-, and body mass index-matched controls from the same population. In addition, a subset of 78 renal transplant recipients was followed longitudinally from pretransplantation to 24 months after transplantation. Our data showed that both liver and kidney transplant recipients suffered from gut dysbiosis, including lower microbial diversity, increased abundance of unhealthy microbial species, decreased abundance of important metabolic pathways, and increased prevalence and diversity of antibiotic resistance genes and virulence factors. These changes were found to persist up to 20 years after transplantation. Last, we demonstrated that the use of immunosuppressive drugs was associated with the observed dysbiosis and that the extent of dysbiosis was associated with increased mortality after transplantation. This study represents a step toward potential microbiome-targeted interventions that might influence the outcomes of recipients of solid organ transplantation.}, }
@article {pmid36044059, year = {2022}, author = {Kempski, J and Huber, S}, title = {[Role of the gut microbiome in the pathogenesis and treatment of inflammatory bowel diseases].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {10}, pages = {1022-1027}, pmid = {36044059}, issn = {2731-7099}, mesh = {Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/etiology ; Intestines ; }, abstract = {Inflammatory bowel diseases (IBD) are systemic diseases that mainly manifest in the gastrointestinal tract. Due to chronically impaired intestinal homeostasis, they often require permanent and in some cases systemic therapy. The exact causes of IBD are largely unknown. It is postulated that these complex diseases arise in genetically susceptible individuals through a misdirected immune response, promoted by barrier defects, environmental toxins, and the gut microbiome. In this regard, the importance of the microbiome and its pathogenic changes (dysbiosis) in the pathogenesis of IBD is increasingly coming into focus. This review article presents the current state of research on the role of the microbiome in the development of IBD. Therapeutic approaches aimed at correcting intestinal dysbiosis are also discussed.}, }
@article {pmid36043345, year = {2022}, author = {Tan, B and Liu, YX and Tang, H and Chen, D and Xu, Y and Chen, MJ and Li, Y and Wang, MZ and Qian, JM}, title = {Gut microbiota shed new light on the management of immune-related adverse events.}, journal = {Thoracic cancer}, volume = {13}, number = {19}, pages = {2681-2691}, pmid = {36043345}, issn = {1759-7714}, mesh = {Animals ; Anti-Bacterial Agents ; *Colitis/chemically induced/therapy ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors/adverse effects ; Mice ; Prebiotics ; }, abstract = {Immunotherapy has dramatically revolutionized the therapeutic landscape for patients with cancer. Although immune checkpoint inhibitors are now accepted as effective anticancer therapies, they introduce a novel class of toxicity, termed immune-related adverse events, which can lead to the temporary or permanent discontinuation of immunotherapy and life-threatening tumor progression. Therefore, the effective prevention and treatment of immune-related adverse events is a clinical imperative to maximize the utility of immunotherapies. Immune-related adverse events are related to the intestinal microbiota, baseline gut microbiota composition is an important determinant of immune checkpoint inhibitor-related colitis, and antibiotics exacerbate these undesirable side-effects. Supplementation with specific probiotics reduces immune checkpoint inhibitor-related colitis in mice, and fecal microbiota transplantation has now been shown to effectively treat refractory immune checkpoint inhibitor-related colitis in the clinic. Hence, modifying the microbiota holds great promise for preventing and treating immune-related adverse events. Microbiomes and their metabolites play important roles in the potential underlying mechanisms through interactions with both innate and adaptive immune cells. Here we review the gut microbiota and immune regulation; the changes occurring in the microbiota during immune checkpoint inhibitor therapy; the relationship between the microbiota and immune-related adverse events, antibiotics, probiotics/prebiotics, and fecal microbiota transplantation in immune checkpoint inhibitor-related colitis; and the protective mechanisms mediated by the microbiome and metabolites in immune-related adverse events.}, }
@article {pmid36042459, year = {2022}, author = {Jiang, H and Peng, Y and Zhang, W and Chen, Y and Jiang, Q and Zhou, Y}, title = {Gut microbiome-targeted therapies in liver cirrhosis: a protocol for systematic review and meta-analysis.}, journal = {Systematic reviews}, volume = {11}, number = {1}, pages = {181}, pmid = {36042459}, issn = {2046-4053}, mesh = {*Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis/therapy ; Meta-Analysis as Topic ; Prebiotics ; *Probiotics/therapeutic use ; Systematic Reviews as Topic ; }, abstract = {BACKGROUND: Microbiome-targeted therapies (MTTs), including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), have been proposed as a potential treatment for cirrhosis via modulation of gut microbiome, while the impact of gut microflora alteration on liver function in cirrhosis trajectory is unclear, and no related systematic review has been published. We aim to comprehensively assess the effects of MTTs in patients with liver cirrhosis.<br><br>METHODS: We will search databases of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) with no time restriction. Only randomized controlled trials published in English will be included. Two independent reviewers will be responsible for study identification and selection, data extraction, and risk of bias assessment, with discrepancies resolved by consensus or referral to a third author. Heterogeneity of studies will be examined using Cochrane Q-test and I[2] statistics. The data will be pooled using either a fixed- or random-effects model based on I[2] statistics. The results will be presented as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). We will perform subgroup analysis on the type of MTTs and assess the reporting biases. Sensitivity analysis will be conducted to test the stability of each outcome result.<br><br>DISCUSSION: There is no current study about the role of MTTs in developing the liver function, and the therapeutic effects of MTTs are inconsistent. By investigating the liver-specific indicators when treating with multiple MTTs on course of cirrhosis, our findings will give more conclusive and stronger evidence about the efficacy of MTTs and provide new insight into the action mechanisms of these MTTs.<br><br>PROSPERO CRD42021253198.}, }
@article {pmid36042181, year = {2022}, author = {Liu, Y and Jiang, Z and Yang, H and Yuan, J and Zeng, J and Wu, J and Xu, Z}, title = {Gui Shao Tea Extracts Inhibit Gastric Cancer Growth in Vitro and in Vivo and Prolong Survival in Nude Mice.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {27}, number = {8}, pages = {250}, doi = {10.31083/j.fbl2708250}, pmid = {36042181}, issn = {2768-6698}, mesh = {Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Mice ; Mice, Nude ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; *Stomach Neoplasms/pathology ; Tea ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Gui Shao Tea (GST), a long-aged tea with a Chinese herbal aroma, can treat many stubborn and malignant diseases, according to traditional Chinese medicine. This research aimed to discover and define GST, study the anti-gastric cancer effects of GST extracts and preliminarily elucidate the mechanism of action in the PI3K/Akt signaling pathway and the gut microbiota.<br><br>METHODS: GST was analyzed by GC/MS and HPLC. Cell proliferation, the cell cycle and apoptosis were evaluated by a CCK8 assay and flow cytometry. The effects of GST extracts on tumor inhibition and survival time were explored by a gastric cancer xenograft model in nude mice. The PI3K/Akt signaling pathway was assessed by western blotting and immunohistochemistry. Gut microbiota detection and fecal microbiota transplantation were performed to examine whether the tumor inhibition observed in mice was related to gut microbiota changes.<br><br>RESULTS: The ingredients in GST, mostly terpenes and their derivatives, were novel and more concentrated than those in tea made from the branches and leaves of the same plant species, Camellia sinensis, picked and produced the same year, while the levels of polyphenols and alkaloids were significantly reduced. In BGC-823, MGC-803, and SGC-7901 gastric cancer cells, GST extracts significantly inhibited proliferation (p = 0.037), induced G0/G1 arrest (p < 0.001) and promoted early apoptosis (p = 0.041). In mice, gastric tumor growth was significantly inhibited in both the high-dose (HTF) and middle-dose (MTF) GST-fed groups. The inhibition rate in the HTF group was 33.77% on Day 14 (p = 0.042), and that in the MTF group was 55.21% on Day 14 (p = 0.002) and 61.6% on Day 28 (p = 0.008). The survival time of MTF group mice was significantly prolonged by 22.2% (p = 0.013). GST extracts inhibited the PI3K/AKT signaling pathway in gastric cancer cells (p = 0.016) and tissues (p = 0.029), downregulated the protein p-Rb and further downregulated E2F1, thereby affecting the cell cycle and proliferation. GST extracts altered the gut microbiota in mice, but these alterations alone were insufficient to inhibit gastric cancer growth.<br><br>CONCLUSIONS: We confirmed the anti-gastric cancer effects of GST extracts, which might provide new approaches and methods for research and development of gastric cancer drugs.}, }
@article {pmid36040503, year = {2022}, author = {Noureldein, M and Nawfal, R and Bitar, S and Maxwell, SS and Khurana, I and Kassouf, HK and Khuri, FR and El-Osta, A and Eid, AA}, title = {Intestinal microbiota regulates diabetes and cancer progression by IL-1β and NOX4 dependent signaling cascades.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {79}, number = {9}, pages = {502}, pmid = {36040503}, issn = {1420-9071}, mesh = {Animals ; Bacteria/genetics ; Butyrates/pharmacology ; Carcinogenesis ; *Diabetes Mellitus, Experimental/complications ; *Diabetes Mellitus, Type 2/complications ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; NADPH Oxidase 4/genetics ; RNA, Ribosomal, 16S ; }, abstract = {Diabetes changes the host microbiota, a condition known as dysbiosis. Dysbiosis is an important factor for the pathogenesis of diabetes and colorectal cancer (CRC). We aimed at identifying the microbial signature associated with diabetes and CRC; and identifying the signaling mechanism altered by dysbiosis and leading to CRC progression in diabetes. MKR mice that can spontaneously develop type 2 diabetes were used. For CRC induction, another subset of mice was treated with azoxymethane and dextran sulfate sodium. To identify the role of microbiota, microbiota-depleted mice were inoculated with fecal microbial transplant from diabetic and CRC mice. Further, a mouse group was treated with probiotics. At the end of the treatment, 16S rRNA sequencing was performed to identify microbiota in the fecal samples. Blood was collected, and colons were harvested for molecular, anatomical, and histological analysis. Our results show that diabetes is associated with a microbial signature characterized by reduction of butyrate-forming bacteria. This dysbiosis is associated with gastrointestinal complications reflected by a reduction in colon lengths. These changes are reversed upon treatment with probiotics, which rectified the observed dysbiosis. Inoculation of control mice with diabetic or cancer microbiota resulted in the development of increased number of polyps. Our data also show that inflammatory cytokines (mainly interleukin (IL)-1β) and NADPH oxidase (NOX)4 are over-expressed in the colon tissues of diabetic mice. Collectively our data suggest that diabetes is associated with dysbiosis characterized by lower abundance of butyrate-forming bacteria leading to over-expression of IL-1β and NOX4 leading to gastrointestinal complications and CRC.}, }
@article {pmid36037843, year = {2023}, author = {Rathour, D and Shah, S and Khan, S and Singh, PK and Srivastava, S and Singh, SB and Khatri, DK}, title = {Role of gut microbiota in depression: Understanding molecular pathways, recent research, and future direction.}, journal = {Behavioural brain research}, volume = {436}, number = {}, pages = {114081}, doi = {10.1016/j.bbr.2022.114081}, pmid = {36037843}, issn = {1872-7549}, mesh = {Depression ; *Gastrointestinal Microbiome/physiology ; Histones ; Humans ; Kynurenine ; *Probiotics ; RNA, Untranslated ; Tryptophan/metabolism ; }, abstract = {Gut microbiota, also known as the "second brain" in humans because of the regulatory role it has on the central nervous system via neuronal, chemical and immune pathways. It has been proven that there exists a bidirectional communication between the gut and the brain. Increasing evidence supports that this crosstalk is linked to the etiology and treatment of depression. Reports suggest that the gut microbiota control the host epigenetic machinery in depression and gut dysbiosis causes negative epigenetic modifications via mechanisms like histone acetylation, DNA methylation and non-coding RNA mediated gene inhibition. The gut microbiome can be a promising approach for the management of depression. The diet and dietary metabolites like kynurenine, tryptophan, and propionic acid also greatly influence the microbiome composition and thereby, the physiological activities. This review gives a bird-eye view on the pathological updates and currently used treatment approaches targeting the gut microbiota in depression.}, }
@article {pmid36037770, year = {2022}, author = {Han, Q and Deng, LR and Zou, M and Tang, HZ and Huang, CY and Chen, FJ and Tomlinson, B and Li, YH}, title = {Anemoside B4 protects against chronic relapsing colitis in mice by modulating inflammatory response, colonic transcriptome and the gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {106}, number = {}, pages = {154416}, doi = {10.1016/j.phymed.2022.154416}, pmid = {36037770}, issn = {1618-095X}, mesh = {Animals ; *Berberine/pharmacology ; *Colitis/chemically induced/drug therapy/metabolism ; *Colitis, Ulcerative/chemically induced/drug therapy/metabolism ; Colon ; Cytokines/metabolism ; DNA, Ribosomal/metabolism/pharmacology ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Saponins ; Transcriptome ; }, abstract = {BACKGROUND: Anemoside B4 (AB4) is reported to prevent acute colitis when given via intraperitoneal injection by two recent studies. However, whether oral AB4 protects against chronic colitis which resembles the clinical phenotype of ulcerative colitis (UC) and its mechanism of action are largely unknown.<br><br>PURPOSE: To systemically investigate the effects of oral AB4 against chronic colitis and illustrate the underlying mechanism of action.<br><br>METHODS: The preventive, therapeutic, and dose-dependent effects of AB4 against UC were examined in mice with acute or chronic relapsing colitis induced by dextran sulfate sodium (DSS). The inflammatory responses, colonic transcriptome, and 16S rDNA sequencing of the intestinal content of mice were analyzed.<br><br>RESULTS: Oral administration of AB4 alleviated disease severity and colon shortening in mice with chronic relapsing colitis in a dose-dependent manner. The effects of AB4 were comparable to those of two positive-control compounds: tofacitinib and berberine. Unlike tofacitinib, AB4 did not have a deleterious effect on DSS-induced splenic swelling and anemia. Furthermore, AB4 inhibited the inflammatory responses of colitis, as evidenced by in-vivo, ex-vivo, and in-vitro studies. Transcriptomics revealed that AB4 treatment reversed the DSS-mediated decrease in the expression of colonic Pelo, B3gat2 and Mir8010. In addition, AB4 reversed DSS-induced alterations in the intestinal microbiome in mice. Through fecal microbiota transplantation, we proved that AB4 partially exerted its anti-colitis effects by modulating the gut microbiota.<br><br>CONCLUSIONS: We demonstrated for the first time that AB4 has dose-dependent therapeutic effects against chronic relapsing colitis by modulating the inflammatory response, colonic gene expression, and intestinal microbiota.}, }
@article {pmid36035436, year = {2022}, author = {Gubert, C and Choo, JM and Love, CJ and Kodikara, S and Masson, BA and Liew, JJM and Wang, Y and Kong, G and Narayana, VK and Renoir, T and Lê Cao, KA and Rogers, GB and Hannan, AJ}, title = {Faecal microbiota transplant ameliorates gut dysbiosis and cognitive deficits in Huntington's disease mice.}, journal = {Brain communications}, volume = {4}, number = {4}, pages = {fcac205}, pmid = {36035436}, issn = {2632-1297}, abstract = {Huntington's disease is a neurodegenerative disorder involving psychiatric, cognitive and motor symptoms. Huntington's disease is caused by a tandem-repeat expansion in the huntingtin gene, which is widely expressed throughout the brain and body, including the gastrointestinal system. There are currently no effective disease-modifying treatments available for this fatal disorder. Despite recent evidence of gut microbiome disruption in preclinical and clinical Huntington's disease, its potential as a target for therapeutic interventions has not been explored. The microbiota-gut-brain axis provides a potential pathway through which changes in the gut could modulate brain function, including cognition. We now show that faecal microbiota transplant (FMT) from wild-type into Huntington's disease mice positively modulates cognitive outcomes, particularly in females. In Huntington's disease male mice, we revealed an inefficiency of FMT engraftment, which is potentially due to the more pronounced changes in the structure, composition and instability of the gut microbial community, and the imbalance in acetate and gut immune profiles found in these mice. This study demonstrates a role for gut microbiome modulation in ameliorating cognitive deficits modelling dementia in Huntington's disease. Our findings pave the way for the development of future therapeutic approaches, including FMT and other forms of gut microbiome modulation, as potential clinical interventions for Huntington's disease.}, }
@article {pmid36034975, year = {2022}, author = {Qiu, J and Wu, C and Gao, Q and Li, S and Li, Y}, title = {Effect of fecal microbiota transplantation on the TGF-β1/Smad signaling pathway in rats with TNBS-induced colitis.}, journal = {Annals of translational medicine}, volume = {10}, number = {15}, pages = {825}, pmid = {36034975}, issn = {2305-5839}, abstract = {BACKGROUND: Traditional treatments for inflammatory bowel disease (IBD) have adverse side effects, and patients who receive such treatments have high recurrence rates. Fecal microbiota transplantation (FMT) has become an increasingly popular therapeutic option for patients with IBD. However, the mechanism by which FMT alleviates this disease remains unclear.<br><br>METHODS: In this study, a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis was established and used to explore whether the transforming growth factor-beta 1 (TGF-&#x3b2;1)/small mothers against decapentaplegic (Smad) signaling pathway plays a critical role in the FMT alleviation of IBD.<br><br>RESULTS: After the FMT intervention, the disease activity index and histologic scores were significantly decreased. In addition, the TGF-&#x3b2;1 expression level in the FMT group was significantly decreased by approximately 0.72-fold relative to the level in the TNBS colitis group, whereas the Smad3, Smad4, and Smad7 expression levels had increased by approximately 1.21, 1.40, and 1.18 folds, respectively. Similarly, SB431542 inhibited the expression of TGF-&#x3b2;1 and promoted the expression of Smad3, Smad4, and Smad7. Further, the serum levels of the inflammatory cytokines tumor necrosis factor-alpha (TNF-&#x3b1;), interleukin-1&#x3b2; (IL-1&#x3b2;) and interleukin-6 (IL-6) were significantly decreased, whereas that of the interferon-gamma (IFN-&#x3b3;) was not significantly changed after the FMT intervention.<br><br>CONCLUSIONS: These results suggest that FMT inhibits the TGF-&#x3b2;1/Smad signaling pathway to attenuate inflammation.}, }
@article {pmid36034838, year = {2022}, author = {Shi, X and Wu, H and Liu, Y and Huang, H and Liu, L and Yang, Y and Jiang, T and Zhou, M and Dai, M}, title = {Inhibiting vascular smooth muscle cell proliferation mediated by osteopontin via regulating gut microbial lipopolysaccharide: A novel mechanism for paeonol in atherosclerosis treatment.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {936677}, pmid = {36034838}, issn = {1663-9812}, abstract = {Background: Although the gut microbiota is involved in metabolic disease such as atherosclerosis, the underlying mechanism remains elusive. Paeonol (Pae) is a natural phenolic compound isolated from Cortex Moutan, which exhibits anti-atherosclerotic effects. Our previous research demonstrated gut microbiota as a site of Pae action. However, the mechanism by which Pae exerts its anti-atherosclerotic effect by the regulation of gut microbiota remains unclear. Objective: To investigate a potential mechanistic link between the gut microbial lipopolysaccharide (LPS) and vascular smooth muscle cell (VSMC) proliferation in atherosclerosis progression and explore the possible role of Pae. Methods: Experimental atherosclerosis was established in ApoE[-/-] mice, and the atherosclerosis mice were treated with Pae for 4 weeks before being sacrificed for analyses while conducting fecal microbiota transplantation (FMT). The plaque area, levels of serum LPS, expressions of inflammatory factors in serum or aorta, and intestinal barrier permeability were determined. VSMCs were co-cultured with THP-1 cells. CCK-8 assay and EdU staining were performed to assess the proliferative capacity of VSMCs. Immunofluorescence staining was performed to observe the nuclear transfer of p65. Western blotting was used to detect the candidate protein expression level, and quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression level in tissues or cells of each group. Results: During atherosclerosis progression, gut dysbiosis leads to the peripheral accumulation of gut microbial LPS, which acts as a trigger to stimulate osteopontin (OPN) production from circulating monocytes, inducing cell-to-cell crosstalk to promote VSMC proliferation in the aorta. Importantly, the elevation of LPS and OPN concentrations in the blood was also observed in patients with atherosclerosis. Pae could significantly improve atherosclerosis, suppress gut microbial LPS accumulation, and inhibit monocyte/macrophage activation and VSMC proliferation. Conclusions: The present study provides a mechanistic scenario for how long-term stimulation of gut microbial LPS in circulating blood generates a pathological secondary response that leads to abnormal proliferation of VSMCs using high OPN expression in circulating monocytes and suggests a novel strategy for atherosclerosis therapy by remodeling the gut microbiota.}, }
@article {pmid36034698, year = {2022}, author = {Cui, C and Han, Y and Li, H and Yu, H and Zhang, B and Li, G}, title = {Curcumin-driven reprogramming of the gut microbiota and metabolome ameliorates motor deficits and neuroinflammation in a mouse model of Parkinson's disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {887407}, pmid = {36034698}, issn = {2235-2988}, mesh = {1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Creatine ; *Curcumin ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Levodopa ; Metabolome ; Methionine ; Mice ; Mice, Inbred C57BL ; Neuroinflammatory Diseases ; *Neuroprotective Agents ; *Parkinson Disease ; RNA, Ribosomal, 16S ; Sarcosine ; }, abstract = {BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder, accompanied by motor deficits as well as gastrointestinal dysfunctions. Recent studies have proved that the disturbance of gut microbiota and metabolism contributes to the pathogenesis of PD; however, the mechanisms underlying these effects have yet to be elucidated. Curcumin (CUR) has been reported to provide neuroprotective effects on neurological disorders and modulate the gut flora in intestinal-related diseases. Therefore, it is of significant interest to investigate whether CUR could exert a protective effect on PD and whether the effect of CUR is dependent on the intestinal flora and subsequent changes in metabolites.<br><br>METHODS: In this study, we investigated the neuroprotective effects of CUR on a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16S rRNA sequencing was performed to explore the profile of the gut microbiota among controls, MPTP-treated mice and CUR-treated mice. Then, antibiotic treatment (ABX) and fecal microbiota transplantation (FMT) experiments were conducted to examine the role of intestinal microbes on the protective effects of CUR in PD mice. Furthermore, ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics analysis was used to identify the landscape of the CUR-driven serum metabolome. Finally, Pearson's analysis was conducted to investigate correlations between the gut flora-metabolite axis and CUR-driven neuroprotection in PD.<br><br>RESULTS: Our results showed that CUR intervention effectively improved motor deficits, glial cell activation, and the aggregation of &#x3b1;-synuclein (&#x3b1;-syn) in MPTP-treated mice. 16S rRNA sequencing showed elevated abundances of Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Eggerthellaceae but depleted abundances of Aerococcaceae and Staphylococcaceae in CUR-treated mice when compared with MPTP mice. ABX and FMT experiments further confirmed that the gut microbiota was required for CUR-induced protection in PD mice. Serum metabolomics analysis showed that CUR notably upregulated the levels of tyrosine, methionine, sarcosine and creatine. Importantly, strong correlations were identified among crucial taxa (Aerococcaceae, Staphylococcaceae, Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Eggerthellaceae), pivotal metabolites (tyrosine, methionine, sarcosine and creatine) and the motor function and pathological results of mice. CUR treatment led to a rapid increase in the brain levels of tyrosine and levodopa (dopa) these changes were related to the abundances of Lactobacillaceae and Aerococcaceae.<br><br>CONCLUSIONS: CUR exerts a protective effect on the progression of PD by modulating the gut microbiota-metabolite axis. Lactobacillaceae and Aerococcaceae, along with key metabolites such as tyrosine and dopa play a dominant role in CUR-associated neuroprotection in PD mice. Our findings offer unique insights into the pathogenesis and potential treatment of PD.}, }
@article {pmid36034697, year = {2022}, author = {Wang, Z and Li, Y and Liao, W and Huang, J and Liu, Y and Li, Z and Tang, J}, title = {Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {935723}, pmid = {36034697}, issn = {2235-2988}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Gout ; Humans ; *Hyperuricemia ; Prebiotics ; *Probiotics ; Purines ; }, abstract = {The incidence of hyperuricemia (HUA) and gout continuously increases and has become a major public health problem. The gut microbiota, which colonizes the human intestine, has a mutually beneficial and symbiotic relationship with the host and plays a vital role in the host's metabolism and immune regulation. Structural changes or imbalance in the gut microbiota could cause metabolic disorders and participate in the synthesis of purine-metabolizing enzymes and the release of inflammatory cytokines, which is closely related to the occurrence and development of the metabolic immune disease HUA and gout. The gut microbiota as an entry point to explore the pathogenesis of HUA and gout has become a new research hotspot. This review summarizes the characteristics of the gut microbiota in patients with HUA and gout. Meanwhile, the influence of different dietary structures on the gut microbiota, the effect of the gut microbiota on purine and uric acid metabolism, and the internal relationship between the gut microbiota and metabolic endotoxemia/inflammatory factors are explored. Moreover, the intervention effects of probiotics, prebiotics, and fecal microbial transplantation on HUA and gout are also systematically reviewed to provide a gut flora solution for the prevention and treatment of related diseases.}, }
@article {pmid36034447, year = {2022}, author = {Liu, L and Zhang, J and Cheng, Y and Zhu, M and Xiao, Z and Ruan, G and Wei, Y}, title = {Gut microbiota: A new target for T2DM prevention and treatment.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {958218}, pmid = {36034447}, issn = {1664-2392}, mesh = {*Diabetes Mellitus, Type 2 ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome ; Humans ; Insulin ; *Insulin Resistance ; }, abstract = {Type 2 diabetes mellitus (T2DM), one of the fastest growing metabolic diseases, has been characterized by metabolic disorders including hyperglycemia, hyperlipidemia and insulin resistance (IR). In recent years, T2DM has become the fastest growing metabolic disease in the world. Studies have indicated that patients with T2DM are often associated with intestinal flora disorders and dysfunction involving multiple organs. Metabolites of the intestinal flora, such as bile acids (BAs), short-chain fatty acids (SCFAs) and amino acids (AAs)may influence to some extent the decreased insulin sensitivity associated with T2DM dysfunction and regulate metabolic as well as immune homeostasis. In this paper, we review the changes in the gut flora in T2DM and the mechanisms by which the gut microbiota modulates metabolites affecting T2DM, which may provide a basis for the early identification of T2DM-susceptible individuals and guide targeted interventions. Finally, we also highlight gut microecological therapeutic strategies focused on shaping the gut flora to inform the improvement of T2DM progression.}, }
@article {pmid36033885, year = {2022}, author = {Gang, J and Wang, H and Xue, X and Zhang, S}, title = {Microbiota and COVID-19: Long-term and complex influencing factors.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {963488}, pmid = {36033885}, issn = {1664-302X}, abstract = {The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the World Health Organization statistics, more than 500 million individuals have been infected and more than 6 million deaths have resulted worldwide. Although COVID-19 mainly affects the respiratory system, considerable evidence shows that the digestive, cardiovascular, nervous, and reproductive systems can all be involved. Angiotensin-converting enzyme 2 (AEC2), the target of SARS-CoV-2 invasion of the host is mainly distributed in the respiratory and gastrointestinal tract. Studies found that microbiota contributes to the onset and progression of many diseases, including COVID-19. Here, we firstly conclude the characterization of respiratory, gut, and oral microbial dysbiosis, including bacteria, fungi, and viruses. Then we explore the potential mechanisms of microbial involvement in COVID-19. Microbial dysbiosis could influence COVID-19 by complex interactions with SARS-CoV-2 and host immunity. Moreover, microbiota may have an impact on COVID-19 through their metabolites or modulation of ACE2 expression. Subsequently, we generalize the potential of microbiota as diagnostic markers for COVID-19 patients and its possible association with post-acute COVID-19 syndrome (PACS) and relapse after recovery. Finally, we proposed directed microbiota-targeted treatments from the perspective of gut microecology such as probiotics and prebiotics, fecal transplantation and antibiotics, and other interventions such as traditional Chinese medicine, COVID-19 vaccines, and ACE2-based treatments.}, }
@article {pmid36032720, year = {2022}, author = {Dong, Y and Xu, T and Xiao, G and Hu, Z and Chen, J}, title = {Opportunities and challenges for synthetic biology in the therapy of inflammatory bowel disease.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {10}, number = {}, pages = {909591}, pmid = {36032720}, issn = {2296-4185}, abstract = {Inflammatory bowel disease (IBD) is a complex, chronic intestinal inflammatory disorder that primarily includes Crohn's disease (CD) and ulcerative colitis (UC). Although traditional antibiotics and immunosuppressants are known as the most effective and commonly used treatments, some limitations may be expected, such as limited efficacy in a small number of patients and gut flora disruption. A great many research studies have been done with respect to the etiology of IBD, while the composition of the gut microbiota is suggested as one of the most influential factors. Along with the development of synthetic biology and the continuing clarification of IBD etiology, broader prospects for novel approaches to IBD therapy could be obtained. This study presents an overview of the currently existing treatment options and possible therapeutic targets at the preclinical stage with respect to microbial synthesis technology in biological therapy. This study is highly correlated to the following topics: microbiota-derived metabolites, microRNAs, cell therapy, calreticulin, live biotherapeutic products (LBP), fecal microbiota transplantation (FMT), bacteriophages, engineered bacteria, and their functional secreted synthetic products for IBD medical implementation. Considering microorganisms as the main therapeutic component, as a result, the related clinical trial stability, effectiveness, and safety analysis may be the major challenges for upcoming research. This article strives to provide pharmaceutical researchers and developers with the most up-to-date information for adjuvant medicinal therapies based on synthetic biology.}, }
@article {pmid36032113, year = {2022}, author = {Kleber, KT and Iranpur, KR and Perry, LM and Cruz, SM and Razmara, AM and Culp, WTN and Kent, MS and Eisen, JA and Rebhun, RB and Canter, RJ}, title = {Using the canine microbiome to bridge translation of cancer immunotherapy from pre-clinical murine models to human clinical trials.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {983344}, pmid = {36032113}, issn = {1664-3224}, support = {R03 CA252793/CA/NCI NIH HHS/United States ; T32 CA251007/CA/NCI NIH HHS/United States ; U01 CA224166/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Bone Neoplasms ; Clinical Trials as Topic ; Disease Models, Animal ; Dogs ; Humans ; Immunologic Factors ; Immunotherapy ; Mice ; *Microbiota ; Neoplasm Recurrence, Local ; }, abstract = {The microbiome has clearly been established as a cutting-edge field in tumor immunology and immunotherapy. Growing evidence supports the role of the microbiome in immune surveillance, self-tolerance, and response to immune checkpoint inhibitors such as anti PD-L1 and CTLA-4 blockade (1-6). Moreover, recent studies including those using fecal microbial transplantation (FMT) have demonstrated that response to checkpoint immunotherapies may be conferred or eliminated through gut microbiome modulation (7, 8). Consequently, studies evaluating microbiota-host immune and metabolic interactions remain an area of high impact research. While observations in murine models have highlighted the importance of the microbiome in response to therapy, we lack sufficient understanding of the exact mechanisms underlying these interactions. Furthermore, mouse and human gut microbiome composition may be too dissimilar for discovery of all relevant gut microbial biomarkers. Multiple cancers in dogs, including lymphoma, high grade gliomas, melanomas and osteosarcoma (OSA) closely resemble their human analogues, particularly in regard to metastasis, disease recurrence and response to treatment. Importantly, dogs with these spontaneous cancers also have intact immune systems, suggesting that microbiome analyses in these subjects may provide high yield information, especially in the setting of novel immunotherapy regimens which are currently expanding rapidly in canine comparative oncology (9, 10). Additionally, as onco-microbiotic therapies are developed to modify gut microbiomes for maximal responsiveness, large animal models with intact immune systems will be useful for trialing interventions and monitoring adverse events. Together, pre-clinical mechanistic studies and large animal trials can help fully unlock the potential of the microbiome as a diagnostic and therapeutic target in cancer.}, }
@article {pmid36032108, year = {2022}, author = {He, L and Chen, R and Zhang, B and Zhang, S and Khan, BA and Zhu, D and Wu, Z and Xiao, C and Chen, B and Chen, F and Hou, K}, title = {Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes mellitus.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {930872}, pmid = {36032108}, issn = {1664-3224}, mesh = {Adolescent ; *Diabetes Mellitus, Type 1 ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {UNLABELLED: Type 1 diabetes mellitus (T1DM) is an autoimmune-mediated disease characterized by a reduced or absolute lack of insulin secretion and often associated with a range of vascular and neurological complications for which there is a lack of effective treatment other than lifestyle interventions and pharmacological treatments such as insulin injections. Studies have shown that the gut microbiota is involved in mediating the onset and development of many fecal and extrafecal diseases, including autoimmune T1DM. In recent years, many cases of gut microbiota transplantation for diseases of the bowel and beyond have been reported worldwide, and this approach has been shown to be safe and effective. Here, we conducted an experimental treatment study in two adolescent patients diagnosed with autoimmune T1DM for one year. Patients received one to three rounds of normal fecal microbiota transplants (FMT) and were followed for up to 30 weeks. Clinical outcomes were measured, including biochemical indices, medication regimen, and dosage adjustment. Fecal microbiota metagenomic sequencing after transplantation provides a reference for more reasonable and effective microbiota transplantation protocols to treat autoimmune T1DM. Our results suggest that FMT is an effective treatment for autoimmune T1DM.<br><br>CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn, identifier ChiCTR2100045789.}, }
@article {pmid36030278, year = {2022}, author = {Zhang, Y and Gu, Y and Jiang, J and Cui, X and Cheng, S and Liu, L and Huang, Z and Liao, R and Zhao, P and Yu, J and Wang, J and Jia, Y and Jin, W and Zhou, F}, title = {Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism.}, journal = {NPJ science of food}, volume = {6}, number = {1}, pages = {38}, pmid = {36030278}, issn = {2396-8370}, support = {81774213//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82174299//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81973802//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82074424//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81673949//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Stigmasterol (ST) has been shown to improve both lipid and bile acid (BA) metabolism. However, the mechanism(s) by which ST prevents dyslipidemia via BA metabolism, and the potential involvement of other regulatory mechanisms, remains unclear. Here, we found that ST treatment effectively alleviates lipid metabolism disorder induced by a high-fat diet (HFD). Moreover, we also show that fecal microbiota transplantation from ST-treated rats displays similar protective effects in rats fed on an HFD. Our data confirm that the gut microbiota plays a key role in attenuating HFD-induced fat deposition and metabolic disorders. In particular, ST reverses HFD-induced gut microbiota dysbiosis in rats by reducing the relative abundance of Erysipelotrichaceae and Allobaculum bacteria in the gut. In addition, ST treatment also modifies the serum and fecal BA metabolome profiles in rats, especially in CYP7A1 mediated BA metabolic pathways. Furthermore, chenodeoxycholic acid combined with ST improves the therapeutic effects in HFD-induced dyslipidemia and hepatic steatosis. In addition, this treatment strategy also alters BA metabolism profiles via the CYP7A1 pathway and gut microbiota. Taken together, ST exerts beneficial effects against HFD-induced hyperlipidemia and obesity with the underlying mechanism being partially related to both the reprogramming of the intestinal microbiota and metabolism of BAs in enterohepatic circulation. This study provides a theoretical basis for further study of the anti-obesity effects of ST and consideration of the gut microbiota as a potential target for the treatment of HFD-induced dyslipidemia.}, }
@article {pmid36029281, year = {2022}, author = {Maaloum, M and Afouda, P and Lo, CI and Dubourg, G and Nguyen, TT and Levasseur, A and Saile, R and Raoult, D and Fournier, PE}, title = {Prevotella merdae sp. nov., a new bacterial species isolated from human faeces.}, journal = {FEMS microbiology letters}, volume = {369}, number = {1}, pages = {}, doi = {10.1093/femsle/fnac066}, pmid = {36029281}, issn = {1574-6968}, mesh = {Adult ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; *Fatty Acids ; Feces/microbiology ; Humans ; Phylogeny ; *Prevotella/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Strain Marseille-P4119T was isolated from a faecal sample of a healthy 32-year-old faecal transplant donor. The bacterium was anaerobic, Gram-negative, rod-shaped, non-motile, and did not produce spores. We studied its phenotypic characteristics and sequenced its whole genome. The major fatty acids were C15:0anteiso and C15:0iso. The final genome assembly was 3912650 bp long with a 44.4 mol% G + C content, 3094 protein-coding genes and 74 RNA genes. Strain Marseille-P4119T exhibited a 97.10% 16S rRNA sequence identity and a 29.0% dDDH with Prevotella stercorea CB35T, OrthoANI values ranged from 68.5% with Prevotella enoeca to 77.4% with Prevotella stercorea, the phylogenetically closest bacterial species with standing in nomenclature. Based on the phylogenetic, phenotypic and genomic analyses, we propose the creation of the novel species Prevotella merdae sp. nov. The type strain is Marseille-P4119T (= CSUR P4119T = CECT 9566T).}, }
@article {pmid36028255, year = {2023}, author = {Badran, M and Khalyfa, A and Ericsson, AC and Puech, C and McAdams, Z and Bender, SB and Gozal, D}, title = {Gut microbiota mediate vascular dysfunction in a murine model of sleep apnoea: effect of probiotics.}, journal = {The European respiratory journal}, volume = {61}, number = {1}, pages = {}, pmid = {36028255}, issn = {1399-3003}, support = {R01 HL130984/HL/NHLBI NIH HHS/United States ; R56 HL140548/HL/NHLBI NIH HHS/United States ; RF1 AG061824/AG/NIA NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Disease Models, Animal ; RNA, Ribosomal, 16S ; Mice, Inbred C57BL ; *Sleep Apnea, Obstructive/complications/therapy ; *Probiotics ; Hypoxia ; *Coronary Artery Disease/therapy/complications ; }, abstract = {BACKGROUND: Obstructive sleep apnoea (OSA) is a chronic prevalent condition characterised by intermittent hypoxia (IH), and is associated with endothelial dysfunction and coronary artery disease (CAD). OSA can induce major changes in gut microbiome diversity and composition, which in turn may induce the emergence of OSA-associated morbidities. However, the causal effects of IH-induced gut microbiome changes on the vasculature remain unexplored. Our objective was to assess if vascular dysfunction induced by IH is mediated through gut microbiome changes.<br><br>METHODS: Faecal microbiota transplantation (FMT) was conducted on C57BL/6J na&#xef;ve mice for 6&#x2005;weeks to receive either IH or room air (RA) faecal slurry with or without probiotics (VSL#3). In addition to 16S rRNA amplicon sequencing of their gut microbiome, FMT recipients underwent arterial blood pressure and coronary artery and aorta function testing, and their trimethylamine N-oxide (TMAO) and plasma acetate levels were determined. Finally, C57BL/6J mice were exposed to IH, IH treated with VSL#3 or RA for 6&#x2005;weeks, and arterial blood pressure and coronary artery function assessed.<br><br>RESULTS: Gut microbiome taxonomic profiles correctly segregated IH from RA in FMT mice and the normalising effect of probiotics emerged. Furthermore, IH-FMT mice exhibited increased arterial blood pressure and TMAO levels, and impairments in aortic and coronary artery function (p<0.05) that were abrogated by probiotic administration. Lastly, treatment with VSL#3 under IH conditions did not attenuate elevations in arterial blood pressure or CAD.<br><br>CONCLUSIONS: Gut microbiome alterations induced by chronic IH underlie, at least partially, the typical cardiovascular disturbances of sleep apnoea and can be mitigated by concurrent administration of probiotics.}, }
@article {pmid36028087, year = {2023}, author = {Roth, RS and Liden, M and Huttner, A}, title = {The urobiome in men and women: a clinical review.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {29}, number = {10}, pages = {1242-1248}, doi = {10.1016/j.cmi.2022.08.010}, pmid = {36028087}, issn = {1469-0691}, mesh = {Humans ; Female ; Male ; Retrospective Studies ; *Urinary Tract Infections/prevention &amp; control/microbiology ; Urinary Bladder ; Escherichia coli ; Vagina/microbiology ; }, abstract = {BACKGROUND: Antibiotic therapy alone is unable to control recurrent urinary tract infection (UTI); uropathogens have become multiresistant, and alternative strategies are needed. Far from sterile, the urinary tract contains various low-biomass microbiota, some of whose members appear to protect against clinical UTI.<br><br>OBJECTIVES: This narrative review summarizes (a) the current knowledge of male and female urobiomes in healthy and diseased states, as well as their interplay among sexual partners and (b) clinical trials to date assessing probiotic and other nonantibiotic measures to reduce UTI.<br><br>SOURCES: We used the PubMed interface to search Ovid Medline for articles describing urogenital flora, UTI, UTI dysbiosis, the effects of sexual intercourse on urogenital flora, and clinical trials of probiotics as UTI prophylaxis.<br><br>CONTENT: The healthy urobiome of women contains several Lactobacillus species, some of which may impede Escherichia coli growth in the urinary tract. Although Lactobacilli have been found in male urethral microbiota, their presence in male bladder microbiota is less certain. Distal male urethral and vaginal microbiomes of male and sexual female partners influence one another, but more research is needed on the direct interplay of their full urobiomes. Clinical trials assessing the therapeutic potential of Lactobacilli have been largely underpowered and highly varied in tested formulations and routes and frequencies of administration; as such, they have failed to show a clear benefit. Faecal microbiota transplantation for recurrent Clostridium difficile infection was shown, in a retrospective study of seven patients, to reduce recurrent UTI as a side effect.<br><br>IMPLICATIONS: The urobiome in men and women is complex, variable, and still understudied. Although there is hope that Lactobacilli and faecal microbial transplantation could be future nonantibiotic options for recurrent UTI, both require more pharmacologic and clinical research to identify optimal preparations and routes of administration.}, }
@article {pmid36014889, year = {2022}, author = {Zhai, Z and Dong, W and Sun, Y and Gu, Y and Ma, J and Wang, B and Cao, H}, title = {Vitamin-Microbiota Crosstalk in Intestinal Inflammation and Carcinogenesis.}, journal = {Nutrients}, volume = {14}, number = {16}, pages = {}, pmid = {36014889}, issn = {2072-6643}, mesh = {Carcinogenesis ; Dysbiosis/complications ; Humans ; Inflammation/complications ; *Inflammatory Bowel Diseases/complications ; *Microbiota ; Vitamins/therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC) are common diseases of the digestive system. Vitamin deficiencies and gut microbiota dysbiosis have a close relationship with the risk, development, and progression of IBD and CAC. There is a strong link between vitamins and the gut microbiome. Vitamins are extremely crucial for maintaining a healthy gut microbiota, promoting growth and development, metabolism, and innate immunity. Gut microbiota can not only influence the transport process of vitamins, but also produce vitamins to compensate for insufficient food intake. Emerging evidence suggests that oral vitamin supplementation can reduce inflammation levels and improve disease prognosis. In addition, improving the diet structure and consuming foods rich in vitamins not only help to improve the vitamin deficiency, but also help to reduce the risk of IBD. Fecal microbiota transplantation (FMT) and the application of vitamin-producing probiotics can better assist in the treatment of intestinal diseases. In this review, we discuss the interaction and therapeutic roles of vitamins and gut microbiota in IBD and CAC. We also summarize the methods of treating IBD and CAC by modulating vitamins. This may highlight strategies to target gut-microbiota-dependent alterations in vitamin metabolism in the context of IBD and CAC therapy.}, }
@article {pmid36013342, year = {2022}, author = {Al, KF and Chmiel, JA and Stuivenberg, GA and Reid, G and Burton, JP}, title = {Long-Duration Space Travel Support Must Consider Wider Influences to Conserve Microbiota Composition and Function.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {36013342}, issn = {2075-1729}, abstract = {The microbiota is important for immune modulation, nutrient acquisition, vitamin production, and other aspects for long-term human health. Isolated model organisms can lose microbial diversity over time and humans are likely the same. Decreasing microbial diversity and the subsequent loss of function may accelerate disease progression on Earth, and to an even greater degree in space. For this reason, maintaining a healthy microbiome during spaceflight has recently garnered consideration. Diet, lifestyle, and consumption of beneficial microbes can shape the microbiota, but the replenishment we attain from environmental exposure to microbes is important too. Probiotics, prebiotics, fermented foods, fecal microbiota transplantation (FMT), and other methods of microbiota modulation currently available may be of benefit for shorter trips, but may not be viable options to overcome the unique challenges faced in long-term space travel. Novel fermented food products with particular impact on gut health, immune modulation, and other space-targeted health outcomes are worthy of exploration. Further consideration of potential microbial replenishment to humans, including from environmental sources to maintain a healthy microbiome, may also be required.}, }
@article {pmid36012266, year = {2022}, author = {Won, SM and Oh, KK and Gupta, H and Ganesan, R and Sharma, SP and Jeong, JJ and Yoon, SJ and Jeong, MK and Min, BH and Hyun, JY and Park, HJ and Eom, JA and Lee, SB and Cha, MG and Kwon, GH and Choi, MR and Kim, DJ and Suk, KT}, title = {The Link between Gut Microbiota and Hepatic Encephalopathy.}, journal = {International journal of molecular sciences}, volume = {23}, number = {16}, pages = {}, pmid = {36012266}, issn = {1422-0067}, support = {Hallym University Research Fund//Hallym University Research Fund/ ; NRF-2020R1I1A3073530 and NRF-2020R1A6A1A03043026//Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology/ ; }, mesh = {Dysbiosis/complications/therapy ; Fecal Microbiota Transplantation/adverse effects ; Fibrosis ; *Gastrointestinal Microbiome ; *Hepatic Encephalopathy/etiology/therapy ; Humans ; Liver Cirrhosis/complications/therapy ; *Probiotics/therapeutic use ; }, abstract = {Hepatic encephalopathy (HE) is a serious complication of cirrhosis that causes neuropsychiatric problems, such as cognitive dysfunction and movement disorders. The link between the microbiota and the host plays a key role in the pathogenesis of HE. The link between the gut microbiome and disease can be positively utilized not only in the diagnosis area of HE but also in the treatment area. Probiotics and prebiotics aim to resolve gut dysbiosis and increase beneficial microbial taxa, while fecal microbiota transplantation aims to address gut dysbiosis through transplantation (FMT) of the gut microbiome from healthy donors. Antibiotics, such as rifaximin, aim to improve cognitive function and hyperammonemia by targeting harmful taxa. Current treatment regimens for HE have achieved some success in treatment by targeting the gut microbiota, however, are still accompanied by limitations and problems. A focused approach should be placed on the establishment of personalized trial designs and therapies for the improvement of future care. This narrative review identifies factors negatively influencing the gut-hepatic-brain axis leading to HE in cirrhosis and explores their relationship with the gut microbiome. We also focused on the evaluation of reported clinical studies on the management and improvement of HE patients with a particular focus on microbiome-targeted therapy.}, }
@article {pmid36009962, year = {2022}, author = {Beyi, AF and Wannemuehler, M and Plummer, PJ}, title = {Impacts of Gut Microbiota on the Immune System and Fecal Microbiota Transplantation as a Re-Emerging Therapy for Autoimmune Diseases.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, pmid = {36009962}, issn = {2079-6382}, abstract = {The enormous and diverse population of microorganisms residing in the digestive tracts of humans and animals influence the development, regulation, and function of the immune system. Recently, the understanding of the association between autoimmune diseases and gut microbiota has been improved due to the innovation of high-throughput sequencing technologies with high resolutions. Several studies have reported perturbation of gut microbiota as one of the factors playing a role in the pathogenesis of many diseases, such as inflammatory bowel disease, recurrent diarrhea due to Clostridioides difficile infections. Restoration of healthy gut microbiota by transferring fecal material from a healthy donor to a sick recipient, called fecal microbiota transplantation (FMT), has resolved or improved symptoms of autoimmune diseases. This (re)emerging therapy was approved for the treatment of drug-resistant recurrent C. difficile infections in 2013 by the U.S. Food and Drug Administration. Numerous human and animal studies have demonstrated FMT has the potential as the next generation therapy to control autoimmune and other health problems. Alas, this new therapeutic method has limitations, including the risk of transferring antibiotic-resistant pathogens or transmission of genes from donors to recipients and/or exacerbating the conditions in some patients. Therefore, continued research is needed to elucidate the mechanisms by which gut microbiota is involved in the pathogenesis of autoimmune diseases and to improve the efficacy and optimize the preparation of FMT for different disease conditions, and to tailor FMT to meet the needs in both humans and animals. The prospect of FMT therapy includes shifting from the current practice of using the whole fecal materials to the more aesthetic transfer of selective microbial consortia assembled in vitro or using their metabolic products.}, }
@article {pmid36009566, year = {2022}, author = {Drapkina, OM and Yafarova, AA and Kaburova, AN and Kiselev, AR}, title = {Targeting Gut Microbiota as a Novel Strategy for Prevention and Treatment of Hypertension, Atrial Fibrillation and Heart Failure: Current Knowledge and Future Perspectives.}, journal = {Biomedicines}, volume = {10}, number = {8}, pages = {}, pmid = {36009566}, issn = {2227-9059}, abstract = {Cardiovascular diseases (CVDs) remain the major public health concern worldwide. Over the last two decades, a considerable amount of literature has been published on gut microbiota (GMB) composition and its metabolites, involved in the pathophysiology of CVDs, including arterial hypertension, atrial fibrillation, and congestive heart failure. Although many types of medicines are available to treat CVD, new therapeutic tools are needed to improve clinical outcomes. A challenge that often arises in the researchers' community is how to manipulate the GMB to manage cardiovascular risk factors. Therapeutic strategies designed to manipulate GMB composition and/or its metabolites include dietary approaches, prebiotics/probiotics supplementation, and fecal microbiota transplantation (FMT). In this review, we have focused on three main cardiovascular pathologies (arterial hypertension, atrial fibrillation and heart failure) due to their shared common pathophysiological pathways and structural changes in myocardium, such as inflammation, hypertrophy, fibrosis, and myocardial remodeling. The main aims of the review are: (1) to summarize current knowledge on the key pathophysiologic links between GMB and CVDs, and (2) discuss the results of the studies on GMB modulation for the prevention and treatment of selected CVDs.}, }
@article {pmid36009361, year = {2022}, author = {Thomas, KR and Watt, J and Wu, CMJ and Akinrinoye, A and Amjad, S and Colvin, L and Cowe, R and Duncan, SH and Russell, WR and Forget, P}, title = {Pain and Opioid-Induced Gut Microbial Dysbiosis.}, journal = {Biomedicines}, volume = {10}, number = {8}, pages = {}, pmid = {36009361}, issn = {2227-9059}, abstract = {Opioid-induced dysbiosis (OID) is a specific condition describing the consequences of opioid use on the bacterial composition of the gut. Opioids have been shown to affect the epithelial barrier in the gut and modulate inflammatory pathways, possibly mediating opioid tolerance or opioid-induced hyperalgesia; in combination, these allow the invasion and proliferation of non-native bacterial colonies. There is also evidence that the gut-brain axis is linked to the emotional and cognitive aspects of the brain with intestinal function, which can be a factor that affects mental health. For example, Mycobacterium, Escherichia coli and Clostridium difficile are linked to Irritable Bowel Disease; Lactobacillaceae and Enterococcacae have associations with Parkinson's disease, and Alistipes has increased prevalence in depression. However, changes to the gut microbiome can be therapeutically influenced with treatments such as faecal microbiota transplantation, targeted antibiotic therapy and probiotics. There is also evidence of emerging therapies to combat OID. This review has collated evidence that shows that there are correlations between OID and depression, Parkinson's Disease, infection, and more. Specifically, in pain management, targeting OID deserves specific investigations.}, }
@article {pmid36008350, year = {2022}, author = {Ren, Y and Wang, Z and Xue, J}, title = {[Gut-derived uremic toxin trimethylamine-N-oxide in cardiovascular disease under end-stage renal disease: an injury mechanism and therapeutic target].}, journal = {Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi}, volume = {39}, number = {4}, pages = {848-852}, pmid = {36008350}, issn = {1001-5515}, mesh = {*Cardiovascular Diseases ; Humans ; *Kidney Failure, Chronic ; Methylamines ; Oxides ; Uremic Toxins ; }, abstract = {The main cause of death in patients with end-stage renal disease (ESRD) is cardiovascular disease, and trimethylamine-N-oxide (TMAO) has been found to be one of the specific risk factors in the pathogenic process in recent years. TMAO is derived from intestinal bacterial metabolism of dietary choline, carnitine and other substances and subsequently catalyzed by flavin monooxygenase enzymes in the liver. The changes of intestinal bacteria in ESRD patients have contributed to the accumulation of gut-derived uremic toxins such as TMAO, indoxyl sulfate and indole-3-acetic acid. While elevated TMAO concentration accelerates atherosclerosis through mechanisms such as inflammation, increased scavenger receptor expression, and inhibition of reverse cholesterol transport. In this review, this research introduces the biological function, metabolic processes of TMAO and mechanisms by which TMAO promotes the progression of cardiovascular disease in ESRD patients and summarizes current interventions that may be used to reverse gut microbiota disturbances, such as activated carbon, fecal microbial transplantation, dietary improvement, probiotic and probiotic introduction. It also focuses on exploring intervention targets to reduce the gut-derived uremic toxin TMAO in order to explore the possibility of more cardiovascular disease treatments for ESRD patients.}, }
@article {pmid36006314, year = {2022}, author = {Tuniyazi, M and Hu, X and Fu, Y and Zhang, N}, title = {Canine Fecal Microbiota Transplantation: Current Application and Possible Mechanisms.}, journal = {Veterinary sciences}, volume = {9}, number = {8}, pages = {}, pmid = {36006314}, issn = {2306-7381}, abstract = {Fecal microbiota transplantation (FMT) is an emerging therapeutic option for a variety of diseases, and is characterized as the transfer of fecal microorganisms from a healthy donor into the intestinal tract of a diseased recipient. In human clinics, FMT has been used for treating diseases for decades, with promising results. In recent years, veterinary specialists adapted FMT in canine patients; however, compared to humans, canine FMT is more inclined towards research purposes than practical applications in most cases, due to safety concerns. Therefore, in order to facilitate the application of fecal transplant therapy in dogs, in this paper, we review recent applications of FMT in canine clinical treatments, as well as possible mechanisms that are involved in the process of the therapeutic effect of FMT. More research is needed to explore more effective and safer approaches for conducting FMT in dogs.}, }
@article {pmid36005641, year = {2022}, author = {Cai, L and Li, M and Zhou, S and Zhu, X and Zhang, X and Xu, Q}, title = {Trans-Species Fecal Transplant Revealed the Role of the Gut Microbiome as a Contributor to Energy Metabolism and Development of Skeletal Muscle.}, journal = {Metabolites}, volume = {12}, number = {8}, pages = {}, pmid = {36005641}, issn = {2218-1989}, abstract = {The aim of this study was to investigate the influence of the exogenous gut microbiome at early life stages on the development of mice skeletal muscle in adulthood. First, the characteristics of skeletal muscle and the gut microbiota composition of the gut microbiota donors—Erhualian (EH) pigs (a native Chinese breed)—were studied. EH pigs had significantly higher fiber densities and thinner fiber diameters than Duroc × Landrace × Yorkshire crossed (DLY) pigs (p < 0.05). The expression levels of genes related to oxidized muscle fibers, mitochondrial function, and glucose metabolism in the skeletal muscle of EH pigs were significantly higher than those in DLY pigs (p < 0.05). Moreover, the abundances of 8 gut microbial phyla and 35 genera correlated with the skeletal muscle fiber diameters and densities exhibited significant differences (p < 0.05) between EH and DLY pigs. Subsequently, newborn mice were treated with saline (CG) and fecal microbiota suspensions collected from EH pigs (AG), respectively, for 15 days, starting from the day of birth. In adulthood (60 days), the relative abundances of Parabacteroides, Sutterella, and Dehalobacterium were significantly higher in the feces of the AG mice than those of the CG mice. The microbes contribute to improved functions related to lipid and carbohydrate metabolism. The weight, density, and gene expression related to the oxidized muscle fibers, mitochondrial function, and glucose metabolism of the AG group were significantly higher than those of the CG group (p < 0.05), whereas the fiber diameters in the skeletal muscle of the AG mice were significantly lower (p < 0.05) than those of the CG mice. These results suggested that intervention with exogenous microbiota at early stages of life can affect the fiber size and energy metabolism of their skeletal muscle.}, }
@article {pmid36004633, year = {2022}, author = {Lee, MR and Kim, ES}, title = {[Clostridioides Infection in Patients with Inflammatory Bowel Disease].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {80}, number = {2}, pages = {66-71}, doi = {10.4166/kjg.2022.097}, pmid = {36004633}, issn = {2233-6869}, mesh = {Chronic Disease ; *Clostridioides difficile ; *Clostridium Infections/diagnosis ; *Colitis, Ulcerative/complications/diagnosis/drug therapy ; Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases/complications/diagnosis/therapy ; }, abstract = {Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal tract, which is often accompanied by altered gut microbial composition. Gut dysbiosis in IBD is considered to be the reason for the high risk of Clostridioides difficile infection (CDI) in patients with IBD. Therefore, CDI should be evaluated in IBD patients with a symptom flare. Medical treatment of non-severe CDI in IBD is similar to that in non-IBD patients and includes oral vancomycin or fidaxomicin. The risk of recurrent CDI in IBD is higher than in non-IBD patients and this could be mitigated by fecal microbiota transplantation. As CDI may worsen the clinical outcomes of IBD, patients should be carefully monitored and an escalation of IBD therapy needs to be considered when there is no improvement seen with the antimicrobial treatment of CDI. This review discusses the risk, pathophysiology, diagnosis, and management of CDI in IBD.}, }
@article {pmid36003643, year = {2022}, author = {Veeravalli, S and Varshavi, D and Scott, FH and Varshavi, D and Pullen, FS and Veselkov, K and Phillips, IR and Everett, JR and Shephard, EA}, title = {Treatment of wild-type mice with 2,3-butanediol, a urinary biomarker of Fmo5 [-/-] mice, decreases plasma cholesterol and epididymal fat deposition.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {859681}, pmid = {36003643}, issn = {1664-042X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {We previously showed that Fmo5 [-/-] mice exhibit a lean phenotype and slower metabolic ageing. Their characteristics include lower plasma glucose and cholesterol, greater glucose tolerance and insulin sensitivity, and a reduction in age-related weight gain and whole-body fat deposition. In this paper, nuclear magnetic resonance (NMR) spectroscopy-based metabolite analyses of the urine of Fmo5 [-/-] and wild-type mice identified two isomers of 2,3-butanediol as discriminating urinary biomarkers of Fmo5 [-/-] mice. Antibiotic-treatment of Fmo5 [-/-] mice increased plasma cholesterol concentration and substantially reduced urinary excretion of 2,3-butanediol isomers, indicating that the gut microbiome contributed to the lower plasma cholesterol of Fmo5 [-/-] mice, and that 2,3-butanediol is microbially derived. Short- and long-term treatment of wild-type mice with a 2,3-butanediol isomer mix decreased plasma cholesterol and epididymal fat deposition but had no effect on plasma concentrations of glucose or insulin, or on body weight. In the case of long-term treatment, the effects were maintained after withdrawal of 2,3-butanediol. Short-, but not long-term treatment, also decreased plasma concentrations of triglycerides and non-esterified fatty acids. Fecal transplant from Fmo5 [-/-] to wild-type mice had no effect on plasma cholesterol, and 2,3-butanediol was not detected in the urine of recipient mice, suggesting that the microbiota of the large intestine was not the source of 2,3-butanediol. However, 2,3-butanediol was detected in the stomach of Fmo5 [-/-] mice, which was enriched for Lactobacillus genera, known to produce 2,3-butanediol. Our results indicate a microbial contribution to the phenotypic characteristic of Fmo5 [-/-] mice of decreased plasma cholesterol and identify 2,3-butanediol as a potential agent for lowering plasma cholesterol.}, }
@article {pmid36003287, year = {2022}, author = {Xie, YC and Jing, XB and Chen, X and Chen, LZ and Zhang, SH and Cai, XB}, title = {Fecal microbiota transplantation treatment for type 1 diabetes mellitus with malnutrition: a case report.}, journal = {Therapeutic advances in chronic disease}, volume = {13}, number = {}, pages = {20406223221117449}, pmid = {36003287}, issn = {2040-6223}, abstract = {Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease. Not only genetics, but the intestinal environment affected by gut microbiota is also the key to pathogenesis. Besides the occurrence of diabetes, gut microbiota dysbiosis may also contribute to the development of diabetes-related complications. Fecal microbiota transplantation (FMT) is an emerging technique that had shown its potential as a treatment for metabolic disease. Here, we report the first case of T1DM with malnutrition and gastrointestinal symptoms treated with FMT. A 24-year-old T1DM patient suffered from poor blood glucose control, recurrent nausea and vomiting, severe malnutrition, and intractable constipation after insulin treatment. The clinical response of the patients after FMT was well, especially nausea and vomiting were significantly relieved. In addition, constipation, nutritional status, and blood glucose control (fasting blood glucose, HbA1c) gradually improved. A degree of similarity was found in gut microbiota composition between the patient and healthy donor after FMT while it was totally different before the treatment. Furthermore, pathway function analysis of MetaCYC database implies that the potential mechanism of the response of FMT may be driven by specific bacteria involved in several metabolic pathways that need further exploration. To sum up, we believe that the reconstruction of intestinal flora by FMT may be a new choice for the treatment of T1DM patients with malnutrition.}, }
@article {pmid35994399, year = {2022}, author = {Caruso, S and Marrone, G and Gentile, G}, title = {Case 305: Loeffler Endocarditis.}, journal = {Radiology}, volume = {304}, number = {3}, pages = {736-742}, doi = {10.1148/radiol.210453}, pmid = {35994399}, issn = {1527-1315}, mesh = {Echocardiography ; Heart Ventricles ; Humans ; *Hypereosinophilic Syndrome/complications/diagnostic imaging ; Male ; Stroke Volume ; *Ventricular Function, Left ; }, abstract = {A 27-year-old man was admitted to the emergency department with fever and thoracic pain. In the previous 6 months, the patient lost a substantial amount of weight (12 kg). His family history was negative for cardiac disease. Electrocardiography revealed sinus rhythm and diffuse T-wave inversion. Two-dimensional echocardiography was performed and revealed normal left systolic function (ejection fraction, 60%). Laboratory tests showed elevated levels of high-sensitivity cardiac troponin (1.07 ng/mL; normal value, <0.015 ng/mL), high levels of C-reactive protein (16 mg/dL; normal range, 0-5 mg/dL), and leukocytosis with an eosinophilia level of 8710/μL (normal level, <400/μL). Parasitic and infectious diseases (Toxocara canis, strongyloides, filariasis, cysticercosis, fasciola, trichinella, echinococcosis) were excluded based on blood and fecal test results. Corticosteroid therapy was started, and the patient was dismissed. A few days later, he was readmitted to the emergency department with a headache and suddenly blurred vision. Neurologic and ophthalmologic findings were normal, and MRI of the brain was performed. Cardiac MRI was performed 2 days later and revealed the following quantitative results: (a) left ventricular end-diastolic volume (LVDV) of 165 mL (LVDV/body surface area [BSA], 89 mL/m[2]; normal range, 64-100 mL/m[2]), left ventricular end-systolic volume (LVSV) of 80 mL (LVSV/BSA, 43 mL/m[2]; normal range, 17-39 mL/m[2]), stroke volume (SV) of 85 mL (SV/BSA, 46 mL/m[2]; normal range, 43-67 mL/m[2]), and ejection fraction of 52% and (b) right ventricular end-diastolic volume (RVDV) of 163 mL (RVDV/BSA, 88 mL/m[2]; normal range, 63-111 mL/m[2]), right ventricular end-systolic volume (RVSV) of 81 mL (RVSV/BSA, 44 mL/m[2]; normal range, 32-92 mL/m[2]), stroke volume (SV) of 82 mL (SV/BSA, 44 mL/m[2]; normal range, 39-71 mL/m[2]), and ejection fraction of 50%.}, }
@article {pmid35992705, year = {2022}, author = {Qin, S and Wang, Y and Wang, S and Ning, B and Huai, J and Yang, H}, title = {Gut microbiota in women with gestational diabetes mellitus has potential impact on metabolism in pregnant mice and their offspring.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {870422}, pmid = {35992705}, issn = {1664-302X}, abstract = {Studies have shown that gestational diabetes mellitus (GDM) is closely related to abnormalities in the gut microbiota, and the offspring of these women have an increased risk of diabetes. There is no direct evidence of whether bacteria in women with GDM colonize the intestinal tract of offspring and cause hyperglycemia. In this fecal microbiota transplantation (FMT), pregnant mouse model study, two groups of germ-free (GF) mice after FMT showed different colonization patterns of gut microbiota and phenotype. Compared with the control group (healthy-FMT), we found in the GDM-FMT group as a lower relative abundance of Akkermansia and Faecalibacterium; a lower content of short-chain fatty acids and naringenin in feces; an elevated blood glucose; an inflammatory factor expression (TNF-α, CXCL-15, and IL-6), and a hepatic fat deposition. In addition, the influence of the gut microbiota continued in offspring. The gut microbiota of the offspring of GDM-FMT mice was still different from that of the control group as a lower relative abundance of Akkermansia and Parvibacter; and a higher relative abundance of bacteria such as Oscillibacter, Romboutsia, and Harryflintia. In addition, the offspring of GDM-FMT mice had higher body weight and blood glucose levels than the control offspring.}, }
@article {pmid35988752, year = {2022}, author = {Santana, AB and Souto, BS and Santos, NCM and Pereira, JA and Tagliati, CA and Novaes, RD and Corsetti, PP and de Almeida, LA}, title = {Murine response to the opportunistic bacterium Pseudomonas aeruginosa infection in gut dysbiosis caused by 5-fluorouracil chemotherapy-induced mucositis.}, journal = {Life sciences}, volume = {307}, number = {}, pages = {120890}, doi = {10.1016/j.lfs.2022.120890}, pmid = {35988752}, issn = {1879-0631}, mesh = {Animals ; *Antineoplastic Agents/therapeutic use ; Bacteria ; Dysbiosis/microbiology ; Fluorouracil/metabolism ; Intestinal Mucosa/metabolism ; Mice ; Mice, Inbred BALB C ; *Mucositis/chemically induced/drug therapy ; *Opportunistic Infections/complications/metabolism/pathology ; Phylogeny ; *Pseudomonas Infections/drug therapy ; Pseudomonas aeruginosa ; }, abstract = {AIMS: This manuscript aims to explain the relationship between mucositis caused by 5-FU over gut bacterial species and susceptibility to opportunistic infection caused by P. aeruginosa.<br><br>MAIN METHODS: BALB/c mice were intraperitoneally treated with PBS or 5-FU. Bodyweight and faecal consistency were checked daily. Mice faecal DNA was extracted, and bacterial phylogenetic groups were analysed using qPCR or high-throughput sequencing. Immunofluorescence was used to evaluate BMDM activation by mice-treated faecal content. Mice were challenged intratracheally with virulent P. aeruginosa, and the CFU and histology were analysed. Faecal microbiota were transplanted to evaluate the gut microbiota and resistance to pulmonary P. aeruginosa recovery.<br><br>KEY FINDINGS: The animals treated with 5-FU presented mucositis with great weight loss, altered faecal consistency, bacterial gut dysbiosis and histological changes in the intestinal mucosa. Mice under 5-FU treatment were more susceptible to lung infection by the bacteria P. aeruginosa and had more extensive tissue damage during their lung infection with greater pro-inflammatory gene expression. It was observed that the mucositis remained in the groups with 5-FU even with the FMT. The results caused by mucositis in animals that received allogeneic FMT were reversed, however, with a decrease in P. aeruginosa susceptibility in animals treated with 5-FU and allogeneic FMT compared to animals treated with 5-FU and autologous FMT.<br><br>SIGNIFICANCE: Treatment with 5-FU in a murine model makes it more susceptible to pulmonary infection by the bacterium P. aeruginosa, FMT offers an opportunity to protect against this susceptibility to infection.}, }
@article {pmid35987480, year = {2022}, author = {Ren, Z and Chen, S and Lv, H and Peng, L and Yang, W and Chen, J and Wu, Z and Wan, C}, title = {Effect of Bifidobacterium animalis subsp. lactis SF on enhancing the tumor suppression of irinotecan by regulating the intestinal flora.}, journal = {Pharmacological research}, volume = {184}, number = {}, pages = {106406}, doi = {10.1016/j.phrs.2022.106406}, pmid = {35987480}, issn = {1096-1186}, mesh = {*Bifidobacterium animalis ; CD8-Positive T-Lymphocytes ; *Gastrointestinal Microbiome ; Irinotecan/pharmacology ; Phosphatidylinositol 3-Kinases ; *Probiotics/therapeutic use ; Proto-Oncogene Proteins c-akt ; Transforming Growth Factor beta ; }, abstract = {The gut microbiota plays a role in tumor therapy by participating in immune regulation. Here, we demonstrated through 8-day probiotic supplementation experiments and fecal microbiota transplantation experiments that Bifidobacterium animalis subsp. lactis SF enhanced the antitumor effect of irinotecan and prevented the occurrence of intestinal damage by modulating the gut microbiota and reducing the relative abundance of pro-inflammatory microbiota. Therefore, the intestinal inflammation was inhibited, the TGF-β leakage was reduced, and the PI3K/AKT pathway activation was inhibited. Thus, the tumor apoptotic autophagy was finally promoted. Simultaneously, the reduction of TGF-β relieved the immunosuppression caused by CPT-11, promoted the differentiation of CD4[+] and CD8[+] T cells in tumor tissue, and consequently inhibited tumor growth and invasion. This study disclosed the mechanism of B. lactis SF assisting CPT-11 in antitumor activity and suggested that B. lactis SF plays a new role in anticancer effects as a nutritional intervention.}, }
@article {pmid35985814, year = {2022}, author = {Holle, J and Bartolomaeus, H and Löber, U and Behrens, F and Bartolomaeus, TUP and Anandakumar, H and Wimmer, MI and Vu, DL and Kuhring, M and Brüning, U and Maifeld, A and Geisberger, S and Kempa, S and Schumacher, F and Kleuser, B and Bufler, P and Querfeld, U and Kitschke, S and Engler, D and Kuhrt, LD and Drechsel, O and Eckardt, KU and Forslund, SK and Thürmer, A and McParland, V and Kirwan, JA and Wilck, N and Müller, D}, title = {Inflammation in Children with CKD Linked to Gut Dysbiosis and Metabolite Imbalance.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {33}, number = {12}, pages = {2259-2275}, pmid = {35985814}, issn = {1533-3450}, mesh = {Humans ; *Cardiovascular Diseases ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome/physiology ; Inflammation ; *Renal Insufficiency, Chronic/complications/therapy/metabolism ; Tumor Necrosis Factor-alpha ; Child ; Adolescent ; }, abstract = {BACKGROUND: CKD is characterized by a sustained proinflammatory response of the immune system, promoting hypertension and cardiovascular disease. The underlying mechanisms are incompletely understood but may be linked to gut dysbiosis. Dysbiosis has been described in adults with CKD; however, comorbidities limit CKD-specific conclusions.<br><br>METHODS: We analyzed the fecal microbiome, metabolites, and immune phenotypes in 48 children (with normal kidney function, CKD stage G3-G4, G5 treated by hemodialysis [HD], or kidney transplantation) with a mean&#xb1;SD age of 10.6&#xb1;3.8 years.<br><br>RESULTS: Serum TNF-&#x3b1; and sCD14 were stage-dependently elevated, indicating inflammation, gut barrier dysfunction, and endotoxemia. We observed compositional and functional alterations of the microbiome, including diminished production of short-chain fatty acids. Plasma metabolite analysis revealed a stage-dependent increase of tryptophan metabolites of bacterial origin. Serum from patients on HD activated the aryl hydrocarbon receptor and stimulated TNF-&#x3b1; production in monocytes, corresponding to a proinflammatory shift from classic to nonclassic and intermediate monocytes. Unsupervised analysis of T cells revealed a loss of mucosa-associated invariant T (MAIT) cells and regulatory T cell subtypes in patients on HD.<br><br>CONCLUSIONS: Gut barrier dysfunction and microbial metabolite imbalance apparently mediate the proinflammatory immune phenotype, thereby driving the susceptibility to cardiovascular disease. The data highlight the importance of the microbiota-immune axis in CKD, irrespective of confounding comorbidities.}, }
@article {pmid35985552, year = {2022}, author = {Zhang, M and Ding, L and Zhou, Z and Liu, C and Wang, C and Chen, B and Chen, X and Zhang, Y}, title = {The VEGFR2/mTOR/S6K1 pathway involved in the angiogenic effects of roxarsone in vitro and in vivo.}, journal = {Toxicology}, volume = {478}, number = {}, pages = {153290}, doi = {10.1016/j.tox.2022.153290}, pmid = {35985552}, issn = {1879-3185}, mesh = {Animals ; Cell Proliferation ; Endothelial Cells ; Human Umbilical Vein Endothelial Cells/pathology ; Humans ; Mice ; Neovascularization, Pathologic/pathology ; RNA, Messenger/metabolism ; Rats ; *Roxarsone/metabolism/toxicity ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {Roxarsone, an organoarsenic compound used in poultry industry to increase weight gain, is widely used as a feed additive in some developing countries. Roxarsone has a low absorption rate and is mostly excreted with feces, which could pose a risk to human health through environmental and animal food routes. Roxarsone has been demonstrated to have tumor-promoting and proangiogenic effects. Herein, we report the role of VEGFR2/mTOR/S6K1 signaling in roxarsone-promoted vessel endothelial cell growth and angiogenesis in the Matrigel plug model and the mouse B16 cell tumor transplantation model. In angiogenesis-related experiments in vitro, 1.0 μM roxarsone significantly increased the activity, proliferation, migration, and tube formation of rat vascular endothelial cells. In addition, 1.0 μM roxarsone upregulated the protein levels of mTOR, phosphorylated mTOR, S6K1, and phosphorylated S6K1 and significantly increase the expression of Mtor and S6k1 mRNA. Rapamycin and SU5416 significantly inhibited the effects of 1.0 μM roxarsone on cell growth. Furthermore, the weight, volume, and CD31 expression of B16-F10 xenografts and Matrigel plugs in mice were upregulated by 25 mg/kg roxarsone. The protein and mRNA levels of mTOR, S6K1 and its phosphorylated protein were significantly increased in the roxarsone treatment group in xenografts. SU5416 and a short hairpin RNA targeting Vegfr2 significantly reduced roxarsone-promoted xenograft and Matrigel plug growth. In summary, this study indicated that the VEGFR2/mTOR/S6K1 signaling plays a regulatory role in roxarsone-mediated promotion angiogenesis and enhanced tumor growth.}, }
@article {pmid35985169, year = {2022}, author = {Torres, MT and de la Fuente-Nunez, C}, title = {Molecular tools for probing the microbiome.}, journal = {Current opinion in structural biology}, volume = {76}, number = {}, pages = {102415}, pmid = {35985169}, issn = {1879-033X}, support = {R35 GM138201/GM/NIGMS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; Humans ; *Microbiota ; }, abstract = {The microbiome plays essential roles in health and disease. Our understanding of the imbalances that can arise in the microbiome and their consequences is held back by a lack of technologies that selectively knock out members of these microbial communities. Antibiotics and fecal transplants, the existing methods for manipulating the microbiota of the gastrointestinal tract, are not sufficiently pinpointed to reveal how particular microbial genes, strains, or species affect human health. A toolset for the precise manipulation of the microbiome could significantly advance disease diagnosis and treatment. Here, we provide an overview of current and future strategies for the development of molecular tools that can be used to probe the microbiome without producing off-target effects.}, }
@article {pmid35983067, year = {2022}, author = {Chancharoenthana, W and Sutnu, N and Visitchanakun, P and Sawaswong, V and Chitcharoen, S and Payungporn, S and Schuetz, A and Schultz, MJ and Leelahavanichkul, A}, title = {Critical roles of sepsis-reshaped fecal virota in attenuating sepsis severity.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {940935}, pmid = {35983067}, issn = {1664-3224}, mesh = {Animals ; Cecum/injuries ; Disease Models, Animal ; Feces/microbiology ; Ligation ; Mice ; *Sepsis/microbiology ; }, abstract = {Because studies on all fecal organisms (bacteria, fungi, and viruses) in sepsis are rare and bacteriophages during sepsis might have adapted against gut bacteria with possible pathogenicity, cecal ligation and puncture (CLP; a sepsis mouse model) was evaluated. In fecal bacteriome, sepsis increased Bacteroides and Proteobacteria but decreased Firmicutes, while fecal virome demonstrated increased Podoviridae when compared with sham feces. There was no difference in the fungal microbiome (predominant Ascomycota in both sham and CLP mice) and the abundance of all organisms between sepsis and control groups. Interestingly, the transfers of feces from CLP mice worsened sepsis severity when compared with sham fecal transplantation, as evaluated by mortality, renal injury (serum creatinine and histology), liver damage (liver enzyme and histology), spleen apoptosis, serum cytokines, endotoxemia, and bacteremia. In contrast, the transfers of fecal viral particles from sepsis mice, but not from sham mice, attenuated inflammation in CLP sepsis possibly through the decrease in several fecal pathogenic bacteria (such as Proteobacteria, Gammaproteobacteria, and Prevotellaceae) as evaluated by fecal microbiome analysis. Perhaps the isolation of favorable bacteriophages in sepsis feces and increased abundance ex vivo before oral treatment in a high concentration are beneficial.}, }
@article {pmid35980280, year = {2022}, author = {Park, SH and Lee, JH and Kim, JS and Kim, TJ and Shin, J and Im, JH and Cha, B and Lee, S and Kwon, KS and Shin, YW and Ko, SB and Choi, SH}, title = {Fecal microbiota transplantation can improve cognition in patients with cognitive decline and Clostridioides difficile infection.}, journal = {Aging}, volume = {14}, number = {16}, pages = {6449-6466}, pmid = {35980280}, issn = {1945-4589}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/complications/microbiology/therapy ; Cognition ; *Cognitive Dysfunction/therapy ; *Dementia ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Treatment Outcome ; }, abstract = {After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although the gut microbiome has been associated with cognitive function, it remains to be elucidated whether fecal microbiota transplantation can improve cognition in patients with cognitive decline. The study included 10 patients (age range, 63-90 years; female, 80%) with dementia and severe CDI who were receiving FMT. Also, 10 patients (age range, 62-91; female, 80%) with dementia and severe CDI who were not receiving FMT. They were evaluated using cognitive function tests (Mini-Mental State Examination [MMSE] and Clinical Dementia Rating scale Sum of Boxes [CDR-SB]) at 1 month before and after FMT or antibiotics treatment (control group). The patients' fecal samples were analyzed to compare the composition of their gut microbiota before and 3 weeks after FMT or antibiotics treatment. Ten patients receiving FMT showed significantly improvements in clinical symptoms and cognitive functions compared to control group. The MMSE and CDR-SB of FMT group were improved compare to antibiotics treatment (MMSE: 16.00, median, 13.00-18.00 [IQR] vs. 10.0, median, 9.8-15.3 [IQR]); CDR-SB: 5.50, median, 4.00-8.00 [IQR]) vs. 8.0, median, 7.9-12.5, [IQR]). FMT led to changes in the recipient's gut microbiota composition, with enrichment of Proteobacteria and Bacteroidetes. Alanine, aspartate, and glutamate metabolism pathways were also significantly different after FMT. This study revealed important interactions between the gut microbiome and cognitive function. Moreover, it suggested that FMT may effectively delay cognitive decline in patients with dementia.}, }
@article {pmid35978650, year = {2022}, author = {Quaranta, G and Ianiro, G and De Maio, F and Guarnaccia, A and Fancello, G and Agrillo, C and Iannarelli, F and Bibbo, S and Amedei, A and Sanguinetti, M and Cammarota, G and Masucci, L}, title = {"Bacterial Consortium": A Potential Evolution of Fecal Microbiota Transplantation for the Treatment of Clostridioides difficile Infection.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {5787373}, pmid = {35978650}, issn = {2314-6141}, mesh = {Bacteria/genetics ; Bacteroidetes ; *Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Humans ; Proteobacteria ; Recurrence ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) consists of infusion of feces from a donor to a recipient patient in order to restore the resident microbial population. FMT has shown to be a valid clinical option for Clostridioides difficile infections (CDI). However, this approach shows several criticalities, such as the recruiting and screening of voluntary donors. Our aim was to evaluate the therapeutic efficacy of a synthetic bacterial suspension defined "Bacterial Consortium" (BC) infused in the colon of CDI patients. The suspension was composed by 13 microbial species isolated by culturomics protocols from healthy donors' feces. The efficacy of the treatment was assessed both clinically and by metagenomics typing. Fecal samples of the recipient patients were collected before and after infusion. DNA samples obtained from feces at different time points (preinfusion, 7, 15, 30, and 90 days after infusion) were analyzed by next-generation sequencing. Before infusion, patient 1 showed an intestinal microbiota dominated by the phylum Bacteroidetes. Seven days after the infusion, Bacteroidetes decreased, followed by an implementation of Firmicutes and Verrucomicrobia. Patient 2, before infusion, showed a strong abundance of Proteobacteria and a significant deficiency of Bacteroidetes and Verrucomicrobia. Seven days after infusion, Proteobacteria strongly decreased, while Bacteroidetes and Verrucomicrobia increased. Metagenomics data revealed an "awakening" by microbial species absent or low concentrated at time T0 and present after the infusion. In conclusion, the infusion of selected bacteria would act as a trigger factor for "bacterial repopulation" representing an innovative treatment in patients with Clostridioides difficile infections.}, }
@article {pmid35977507, year = {2022}, author = {MacArthur, MR and Mitchell, SJ and Chadaideh, KS and Treviño-Villarreal, JH and Jung, J and Kalafut, KC and Reynolds, JS and Mann, CG and Trocha, KM and Tao, M and Aye Cho, TZ and Koontanatechanon, A and Yeliseyev, V and Bry, L and Longchamp, A and Ozaki, CK and Lewis, CA and Carmody, RN and Mitchell, JR}, title = {Multiomics assessment of dietary protein titration reveals altered hepatic glucose utilization.}, journal = {Cell reports}, volume = {40}, number = {7}, pages = {111187}, pmid = {35977507}, issn = {2211-1247}, support = {F31 AG064863/AG/NIA NIH HHS/United States ; R01 AG036712/AG/NIA NIH HHS/United States ; R01 DK090629/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Aspartic Acid/metabolism ; Dietary Proteins/metabolism ; Gluconeogenesis ; *Glucose/metabolism ; Glutamic Acid/metabolism ; *Glycerol/metabolism ; Liver/metabolism ; Mice ; Serine/metabolism ; }, abstract = {Dietary protein restriction (PR) has rapid effects on metabolism including improved glucose and lipid homeostasis, via multiple mechanisms. Here, we investigate responses of fecal microbiome, hepatic transcriptome, and hepatic metabolome to six diets with protein from 18% to 0% of energy in mice. PR alters fecal microbial composition, but metabolic effects are not transferable via fecal transplantation. Hepatic transcriptome and metabolome are significantly altered in diets with lower than 10% energy from protein. Changes upon PR correlate with calorie restriction but with a larger magnitude and specific changes in amino acid (AA) metabolism. PR increases steady-state aspartate, serine, and glutamate and decreases glucose and gluconeogenic intermediates. [13]C6 glucose and glycerol tracing reveal increased fractional enrichment in aspartate, serine, and glutamate. Changes remain intact in hepatic ATF4 knockout mice. Together, this demonstrates an ATF4-independent shift in gluconeogenic substrate utilization toward specific AAs, with compensation from glycerol to promote a protein-sparing response.}, }
@article {pmid35975640, year = {2022}, author = {Kang, GU and Park, S and Jung, Y and Jee, JJ and Kim, MS and Lee, S and Lee, DW and Shin, JH and Koh, H}, title = {Exploration of Potential Gut Microbiota-Derived Biomarkers to Predict the Success of Fecal Microbiota Transplantation in Ulcerative Colitis: A Prospective Cohort in Korea.}, journal = {Gut and liver}, volume = {16}, number = {5}, pages = {775-785}, pmid = {35975640}, issn = {2005-1212}, mesh = {Biomarkers ; *Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Prospective Studies ; RNA, Ribosomal, 16S ; Treatment Outcome ; }, abstract = {BACKGROUND/AIMS: Although fecal microbiota transplantation (FMT) has been proven as one of the promising treatments for patients with ulcerative colitis (UC), potential prognostic markers regarding the clinical outcomes of FMT remain elusive.<br><br>METHODS: We collected fecal samples of 10 participants undergoing FMT to treat UC and those from the corresponding donors. We categorized them into two groups: responders and nonresponders. Sequencing of the bacterial 16S rRNA gene was conducted on the samples to explore bacterial composition.<br><br>RESULTS: Analyzing the gut microbiota of patients who showed different outcomes in FMT presented a distinct microbial niche. Source tracking analysis showed the nonresponder group had a higher rate of preservation of donor microbiota, underscoring that engraftment degrees are not one of the major drivers for the success of FMT. At the phylum level, Bacteroidetes bacteria were significantly depleted (p<0.003), and three genera, including Enterococcus, Rothia, and Pediococcus, were enriched in the responder group before FMT (p=0.003, p=0.025, and p=0.048, respectively). Furthermore, we applied a machine learning algorithm to build a prediction model that might allow the prediction of FMT outcomes, which yielded an area under the receiver operating characteristic (ROC) curve of 0.844. Notably, the microbiota-based model was much better at predicting outcomes than the clinical features model (area under the ROC curve=0.531).<br><br>CONCLUSIONS: This study is the first to suggest the significance of indigenous microbiota of recipients as a critical factor. The result highlights that bacterial composition should be evaluated before FMT to select suitable patients and achieve better efficiency.}, }
@article {pmid35975460, year = {2022}, author = {Shang, J and Zhang, Y and Guo, R and Liu, W and Zhang, J and Yan, G and Wu, F and Cui, W and Wang, P and Zheng, X and Wang, T and Dong, Y and Zhao, J and Wang, L and Xiao, J and Zhao, Z}, title = {Gut Microbiome Analysis Can Be Used as a Noninvasive Diagnostic Tool and Plays an Essential Role in the Onset of Membranous Nephropathy.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {9}, number = {28}, pages = {e2201581}, pmid = {35975460}, issn = {2198-3844}, support = {81873611//National Natural Science Foundation of China/ ; 82170738//National Natural Science Foundation of China/ ; //2020 key project of Medical Science and Technology/ ; //Biobank of The First Affiliated Hospital of Zhengzhou University/ ; 2005DKA21300//National Human Genetic Resources Sharing Service Platform/ ; }, mesh = {Animals ; Feces ; *Gastrointestinal Microbiome ; *Glomerulonephritis, Membranous/diagnosis ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Rats ; }, abstract = {Membranous nephropathy (MN) is a common cause of nephrotic syndrome. The aim is to establish a non-invasive diagnostic model of MN using differential gut microbiome analysis, and to explore the relationship between the gut microbiome and MN pathogenesis in vivo. 825 fecal samples from MN patients and healthy participants are collected from multiple medical centers across China. Key operational taxonomic units (OTUs) obtained through 16S rRNA sequencing are used to establish a diagnostic model. A rat model of MN is developed to explore the relationship between the gut microbiome and the pathogenesis of MN. The diversity and richness of the gut microbiome are significantly lower in patients with MN than in healthy individuals. The diagnostic model based on seven OTUs achieves an excellent efficiency of 98.36% in the training group and also achieves high efficiency in cross-regional cohorts. In MN rat model, gut microbiome elimination prevents model establishment, but fecal microbiome transplantation restores the phenotype of protein urine. Gut microbiome analysis can be used as a non-invasive tool for MN diagnosis. The onset of MN depends on the presence of naturally colonized microbiome. Early intervention in the gut microbiome may help reduce urinary protein level in MN.}, }
@article {pmid35973787, year = {2022}, author = {Kedia, S and Virmani, S and K Vuyyuru, S and Kumar, P and Kante, B and Sahu, P and Kaushal, K and Farooqui, M and Singh, M and Verma, M and Bajaj, A and Markandey, M and Sachdeva, K and Das, P and Makharia, GK and Ahuja, V}, title = {Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis: a randomised controlled trial.}, journal = {Gut}, volume = {71}, number = {12}, pages = {2401-2413}, doi = {10.1136/gutjnl-2022-327811}, pmid = {35973787}, issn = {1468-3288}, mesh = {Male ; Humans ; *Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy ; Remission Induction ; Diet ; Anti-Inflammatory Agents ; Treatment Outcome ; }, abstract = {OBJECTIVE: Microbiome and dietary manipulation therapies are being explored for treating ulcerative colitis (UC). We aimed to examine the efficacy of multidonor faecal microbiota transplantation (FMT) and anti-inflammatory diet in inducing remission followed by long-term maintenance with anti-inflammatory diet in patients with mild-moderate UC.<br><br>DESIGN: This open-labelled randomised controlled trial (RCT) randomised patients with mild-moderate (Simple Clinical Colitis Activity Index (SCCAI) 3-9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)>1) on stable baseline medications in 1:1 ratio to FMT and anti-inflammatory diet (FMT-AID) versus optimised standard medical therapy (SMT). The FMT-AID arm received seven weekly colonoscopic infusions of freshly prepared FMT from multiple rural donors(weeks 0-6) with anti-inflammatory diet. Baseline medications were optimised in the SMT arm. Clinical responders (decline in SCCAI>3) at 8&#x2009;weeks in both arms were followed until 48&#x2009;weeks on baseline medications (with anti-inflammatory diet in the FMT-AID arm). Primary outcome measures were clinical response and deep remission (clinical-SCCAI <2;&#x2009;and endoscopic-UCEIS <1) at 8&#x2009;weeks, and deep remission and steroid-free clinical remission at 48&#x2009;weeks.<br><br>RESULTS: Of the 113 patients screened, 73 were randomised, and 66 were included in (35-FMT-AID; 31-SMT) modified intention-to-treat analysis (age-35.7&#xb1;11.1 years; male-60.1%; disease duration-48 (IQR 24-84) months; pancolitis-34.8%; SCCAI-6 (IQR 5-7); UCEIS-4 (IQR 3-5)). Baseline characteristics were comparable. FMT-AID was superior to SMT in inducing clinical response (23/35 (65.7%) vs 11/31 (35.5%), p=0.01, OR 3.5 (95% CI 1.3 to 9.6)), remission (21/35 (60%) vs 10/31 (32.3%), p=0.02, OR 3.2 (95% CI 1.1 to 8.7)) and deep remission (12/33 (36.4%) vs 2/23 (8.7%), p=0.03, OR 6.0 (95% CI 1.2 to 30.2)) at 8&#x2009;weeks. Anti-inflammatory diet was superior to SMT in maintaining deep remission until 48&#x2009;weeks (6/24 (25%) vs 0/27, p=0.007).<br><br>CONCLUSION: Multidonor FMT with anti-inflammatory diet effectively induced deep remission in mild-moderate UC which was sustained with anti-inflammatory diet over 1&#x2009;year.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN15475780.}, }
@article {pmid35973639, year = {2022}, author = {Ciccia, F and Gandolfo, S}, title = {Will fecal microbiota transplantation eventually be an effective therapeutic strategy for systemic lupus erythematosus?.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {242}, number = {}, pages = {109096}, doi = {10.1016/j.clim.2022.109096}, pmid = {35973639}, issn = {1521-7035}, mesh = {Dysbiosis/therapy ; Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Humans ; *Lupus Erythematosus, Systemic/etiology/therapy ; *Microbiota ; Treatment Outcome ; }, abstract = {Gut microbiota dysbiosis serves as a potential trigger that may contribute to metabolic and immune dysregulation that underlies the development of autoimmune diseases. Fecal microbiota transplantation (FMT) is restoration of disturbed microbiota by transplanting foreign gut microbiota from healthy individuals into the gastrointestinal tract of diseased individuals. In this issue of the Journal of Autoimmunity, Huang et al. conducted a 12-week, single-arm pilot clinical trial of oral FMT capsules in patients with active SLE. No serious adverse events (AEs) or deaths were observed and the rate of the primary endpoint (SLE Responder Index-4) was 42.12%. Alternations in bacteria, metabolites and immune parameters were linked to FMT treatment and clinical response in SLE patients. This is the first FMT trial in SLE patients and provides supportive evidence that FMT appears to be a safe, feasible and potentially effective treatment modality in SLE. We await future investigations conducting larger, randomized FMT clinical trials with a longer follow-up to confirm the long-term safety, effectiveness, and potential benefits of FMT-based intervention in SLE and to further demonstrate the underlying microbiological mechanisms.}, }
@article {pmid35969834, year = {2022}, author = {Burgos da Silva, M and Ponce, DM and Dai, A and M Devlin, S and Gomes, ALC and Moore, G and Slingerland, J and Shouval, R and Armijo, GK and DeWolf, S and Fei, T and Clurman, A and Fontana, E and Amoretti, LA and Wright, RJ and Andrlova, H and Miltiadous, O and Perales, MA and Taur, Y and Peled, JU and van den Brink, MRM}, title = {Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease.}, journal = {Blood}, volume = {140}, number = {22}, pages = {2385-2397}, pmid = {35969834}, issn = {1528-0020}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Graft vs Host Disease/microbiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Microbiota ; Feces/microbiology ; Dysbiosis/etiology ; Bacteria ; Butyrates ; }, abstract = {Following allogeneic hematopoietic cell transplantation (allo-HCT), the gastrointestinal (GI) tract is frequently affected by acute graft-versus-host disease (aGVHD), the pathophysiology of which is associated with a dysbiotic microbiome. Since microbial composition varies along the length of the GI tract, the authors hypothesized that microbiome features correlate with the pattern of organ involvement after allo-HCT. We evaluated 266 allo-HCT recipients from whom 1303 stool samples were profiled by 16S ribosomal gene sequencing. Patients were classified according to which organs were affected by aGVHD. In the 20 days prior to disease onset, GVHD patients had lower abundances of members of the class Clostridia, lower counts of butyrate producers, and lower ratios of strict-to-facultative (S/F) anaerobic bacteria compared with allograft recipients who were free of GVHD. GI GVHD patients showed significant reduction in microbial diversity preonset. Patients with lower GI aGVHD had lower S/F anaerobe ratios compared with those with isolated upper GI aGVHD. In the 20 days after disease onset, dysbiosis was observed only in GVHD patients with GI involvement, particularly those with lower-tract disease. Importantly, Clostridial and butyrate-producer abundance as well as S/F anaerobe ratio were predictors of longer overall survival; higher abundance of butyrate producers and higher S/F anaerobe ratio were associated with decreased risk of GVHD-related death. These findings suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD.}, }
@article {pmid35969165, year = {2022}, author = {Letsinger, AC and Yang, F and Menon, R and Little-Letsinger, SE and Granados, JZ and Breidenbach, B and Iyer, AR and Padovani, TC and Nagel, EC and Jayaraman, A and Lightfoot, JT}, title = {Reduced Wheel Running via a High-Fat Diet Is Reversed by a Chow Diet with No Added Benefit from Fecal Microbial Transplants.}, journal = {Medicine and science in sports and exercise}, volume = {54}, number = {9}, pages = {1437-1447}, doi = {10.1249/MSS.0000000000002941}, pmid = {35969165}, issn = {1530-0315}, mesh = {Animals ; *Diet, High-Fat ; *Fatty Liver ; Fecal Microbiota Transplantation ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity ; }, abstract = {PURPOSE: Chronic overfeeding via a high-fat/high-sugar (HFHS) diet decreases wheel running and substantially alters the gut metabolome of C57BL/6J mice. In this study, we tested the hypothesis that fecal microbial transplants can modulate the effect of diet on wheel running.<br><br>METHODS: Singly housed, 6-wk-old male C57BL/6J mice were fed either a grain-based diet (CHOW) or HFHS diet and provided a running wheel for 13 wk. Low-active, HFHS-exposed mice were then either switched to a CHOW diet and given an oral fecal microbial transplant from mice fed the CHOW diet, switched to a CHOW diet and given a sham transplant, or remained on the HFHS diet and given a fecal microbial transplant from mice fed the CHOW diet. Total wheel running, nutrient intake, body composition, fecal microbial composition, fecal metabolite composition, and liver steatosis were measured at various times throughout the study.<br><br>RESULTS: We found that an HFHS diet decreases wheel running activity, increases body fat, and decreases microbial alpha diversity compared with a CHOW diet. Improvements in wheel running, body composition, and microbial alpha diversity were accomplished within 2 wk for mice switched from an HFHS diet to a CHOW diet with no clear evidence of an added benefit from fecal transplants. A fecal transplant from mice fed a CHOW diet without altering diet did not improve wheel running or body composition. Wheel running, body composition, fecal microbial composition, fecal metabolite composition, and liver steatosis percentage were primarily determined by diet.<br><br>CONCLUSIONS: Our results suggest that diet is a primary mediator of wheel running with no clear effect from fecal microbial transplants.}, }
@article {pmid35967846, year = {2022}, author = {Cai, T and Zheng, SP and Shi, X and Yuan, LZ and Hu, H and Zhou, B and Xiao, SL and Wang, F}, title = {Therapeutic effect of fecal microbiota transplantation on chronic unpredictable mild stress-induced depression.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {900652}, pmid = {35967846}, issn = {2235-2988}, mesh = {Animals ; Brain-Derived Neurotrophic Factor/metabolism ; *Depression/etiology/metabolism/therapy ; *Fecal Microbiota Transplantation ; Glucagon-Like Peptide 1 ; Rats ; Rats, Sprague-Dawley ; Serotonin ; Stress, Psychological/therapy ; gamma-Aminobutyric Acid ; }, abstract = {BACKGROUND AND OBJECTIVE: Depression is a complex neuropsychiatric disease with extensive morbidity. Its pathogenesis remains unclear, and it is associated with extremely low rates of cure and complete remission. It is vital to study the pathogenesis of depression to develop effective treatments. This study aimed to explore the therapeutic effects and mechanisms of fecal microbiota transplantation (FMT) for the treatment of depression in rats.<br><br>METHODS: Thirty Sprague-Dawley (SD) rats were randomly divided into three groups: control, chronic unpredictable mild stress (CUMS) to model depression, and CUMS+FMT. For the CUMS and CUMS+FMT groups, after CUMS intervention (four weeks), the rats were given normal saline or FMT (once/week for three weeks), respectively. Behavior, colonic motility, 16S rDNA amplicon sequencing, and untargeted metabolomics on fecal samples were compared between the three rat groups. The following markers were analyzed: 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA), glutamate (Glu), and brain-derived neurotrophic factor (BDNF) levels in the hippocampus; glucagon-like peptide 1 (GLP-1), lipopolysaccharide (LPS), and interleukin (IL)-6 levels in the serum; and GLP-1, GLP-1 receptor (GLP-1R), and serotonin 4 receptor (5-HT4R) levels in colonic tissues.<br><br>RESULTS: FMT improved symptoms of depression and colonic motility in rats exposed to CUMS. The expression levels of 5-HT, GABA, BDNF, and other biochemical indices, significantly differed among the three groups. Meanwhile, the intestinal microbiota in the CUMS+FMT group was more similar to that of the control group with a total of 13 different fecal metabolites.<br><br>CONCLUSION: FMT exerted antidepressant effects on CUMS-induced depression in rats, and the mechanism involved various neurotransmitters, inflammatory factors, neurotrophic factors, and glucagon-like peptides.}, }
@article {pmid35967586, year = {2022}, author = {Wu, H and Guo, K and Zhuo, Z and Zeng, R and Luo, Y and Yang, Q and Li, J and Jiang, R and Huang, Z and Sha, W and Chen, H}, title = {Current therapy option for necrotizing enterocolitis: Practicalities and challenge.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {954735}, pmid = {35967586}, issn = {2296-2360}, abstract = {Necrotizing enterocolitis (NEC) is one of the most prevalent neonatal gastrointestinal disorders. Despite ongoing breakthroughs in its treatment and prevention, the incidence and mortality associated with NEC remain high. New therapeutic approaches, such as breast milk composition administration, stem cell therapy, immunotherapy, and fecal microbiota transplantation (FMT) have recently evolved the prevention and the treatment of NEC. This study investigated the most recent advances in NEC therapeutic approaches and discussed their applicability to bring new insight to NEC treatment.}, }
@article {pmid35966768, year = {2022}, author = {Wang, F and Gu, Y and Xu, C and Du, K and Zhao, C and Zhao, Y and Liu, X}, title = {Transplantation of fecal microbiota from APP/PS1 mice and Alzheimer's disease patients enhanced endoplasmic reticulum stress in the cerebral cortex of wild-type mice.}, journal = {Frontiers in aging neuroscience}, volume = {14}, number = {}, pages = {858130}, pmid = {35966768}, issn = {1663-4365}, abstract = {BACKGROUND AND PURPOSE: The gut-brain axis is bidirectional and the imbalance of the gut microbiota usually coexists with brain diseases, including Alzheimer's disease (AD). Accumulating evidence indicates that endoplasmic reticulum (ER) stress is a core lesion in AD and persistent ER stress promotes AD pathology and impairs cognition. However, whether the imbalance of the gut microbiota is involved in triggering the ER stress in the brain remains unknown.<br><br>MATERIALS AND METHODS: In the present study, fecal microbiota transplantation (FMT) was performed with gut microbiota from AD patients and APP/PS1 mice, respectively, resulting in two mouse models with dysregulated gut microbiota. The ER stress marker protein levels in the cerebral cortex were assessed using western blotting. The composition of the gut microbiota was assessed using 16S rRNA sequencing.<br><br>RESULTS: Excessive ER stress was induced in the cerebral cortex of mice after FMT. Elevated ER stress marker proteins (p-perk/perk, p-eIF2&#x3b1;/eIF2&#x3b1;) were observed, which were rescued by 3,3-dimethyl-1-butanol (DMB). Notably, DMB is a compound that significantly attenuates serum trimethylamine-N-oxide (TMAO), a metabolite of the gut microbiota widely reported to affect cognition.<br><br>CONCLUSION: The findings indicate that imbalance of the gut microbiota induces ER stress in the cerebral cortex, which may be mediated by TMAO.}, }
@article {pmid35966709, year = {2022}, author = {Chen, G and Shi, F and Yin, W and Guo, Y and Liu, A and Shuai, J and Sun, J}, title = {Gut microbiota dysbiosis: The potential mechanisms by which alcohol disrupts gut and brain functions.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {916765}, pmid = {35966709}, issn = {1664-302X}, abstract = {Alcohol use disorder (AUD) is a high-risk psychiatric disorder and a key cause of death and disability in individuals. In the development of AUD, there is a connection known as the microbiota-gut-brain axis, where alcohol use disrupts the gut barrier, resulting in changes in intestinal permeability as well as the gut microbiota composition, which in turn impairs brain function and worsens the patient's mental status and gut activity. Potential mechanisms are explored by which alcohol alters gut and brain function through the effects of the gut microbiota and their metabolites on immune and inflammatory pathways. Alcohol and microbiota dysregulation regulating neurotransmitter release, including DA, 5-HT, and GABA, are also discussed. Thus, based on the above discussion, it is possible to speculate on the gut microbiota as an underlying target for the treatment of diseases associated with alcohol addiction. This review will focus more on how alcohol and gut microbiota affect the structure and function of the gut and brain, specific changes in the composition of the gut microbiota, and some measures to mitigate the changes caused by alcohol exposure. This leads to a potential intervention for alcohol addiction through fecal microbiota transplantation, which could normalize the disruption of gut microbiota after AUD.}, }
@article {pmid35966681, year = {2022}, author = {Jing, H and Chang, Q and Xu, Y and Wang, J and Wu, X and Huang, J and Wang, L and Zhang, Z}, title = {Effect of aging on acute pancreatitis through gut microbiota.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {897992}, pmid = {35966681}, issn = {1664-302X}, abstract = {BACKGROUND: Compared to younger people, older people have a higher risk and poorer prognosis of acute pancreatitis, but the effect of gut microbiota on acute pancreatitis is still unknown. We aim to investigate the effect of aging gut microbiota on acute pancreatitis and explore the potential mechanism of this phenomenon.<br><br>METHODS: Eighteen fecal samples from healthy adult participants, including nine older and nine younger adults were collected. C57BL/6 mice were treated with antibiotics for fecal microbiota transplantation from older and younger participants. Acute pancreatitis was induced by cerulein and lipopolysaccharide in these mice. The effect of the aged gut microbiota was further tested via antibiotic treatment before or after acute pancreatitis induction.<br><br>RESULTS: The gut microbiota of older and younger adults differed greatly. Aged gut microbiota exacerbated acute pancreatitis during both the early and recovery stages. At the same time, the mRNA expression of multiple antimicrobial peptides in the pancreas and ileum declined in the older group. Antibiotic treatment before acute pancreatitis could remove the effect of aging gut microbiota, but antibiotic treatment after acute pancreatitis could not.<br><br>CONCLUSION: Aging can affect acute pancreatitis through gut microbiota which characterizes the deletion of multiple types of non-dominant species. This change in gut microbiota may potentially regulate antimicrobial peptides in the early and recovery stages. The level of antimicrobial peptides has negative correlations with a more severe phenotype.}, }
@article {pmid35965853, year = {2022}, author = {Zhu, R and Xu, X and Lian, S and Cai, M and Zhang, H and Chen, X and Cao, Y}, title = {Intestinal Colonization with Carbapenem-Resistant Enterobacteriaceae in Acute Leukemia Patients: Risk Factors and Molecular Characteristics.}, journal = {Infection and drug resistance}, volume = {15}, number = {}, pages = {4275-4283}, pmid = {35965853}, issn = {1178-6973}, abstract = {BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) colonization is associated with bacterial translocation, which can result in subsequent endogenous CRE infection. In the present study, we aim to investigate the colonization-related risk factors and molecular epidemiological characteristics of CRE in patients with acute leukemia.<br><br>METHODS: From January 2021 to December 2021, acute leukemia patients were screened for CRE by fecal/perianal swabs. We identified the species, carbapenemase-encoding genes, and virulence genes of the colonizing strains and performed antimicrobial susceptibility tests and ERIC-PCR typing. Risk factors for CRE colonization were identified by univariate and multivariate analysis.<br><br>RESULTS: We collected a total of 21 colonizing strains from 320 patients. All strains were resistant to meropenem. Klebsiella pneumoniae was the most abundant species, and ERIC-PCR typing showed low diversity. Univariate analysis showed that age, cephalosporins, penicillins, tigecyclines, and hematopoietic stem cell transplantation status were risk factors for CRE colonization; simultaneously discovered CRE strains played a dominant role in invasive infection of colonized patients. Logistic multivariate regression analysis showed that age, cephalosporins, and tigecyclines were independent risk factors for CRE intestinal colonization.<br><br>CONCLUSION: CRE colonization can increase the incidence of CRE infection in patients with acute leukemia. Early detection of CRE colonization through CRE screening is an important measure to control the spread of CRE.}, }
@article {pmid35965832, year = {2022}, author = {Wei, ZJ and Dong, HB and Ren, YT and Jiang, B}, title = {Efficacy and safety of fecal microbiota transplantation for the induction of remission in active ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Annals of translational medicine}, volume = {10}, number = {14}, pages = {802}, pmid = {35965832}, issn = {2305-5839}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a novel management strategy for ulcerative colitis (UC). However, its effectiveness remains controversial. This study sought to assess the effectiveness of FMT in the treatment of active UC by performing a meta-analysis of randomized controlled trials (RCTs).<br><br>METHODS: We searched the Cochrane, Embase, PubMed, and Web of Science databases from their inception to December 2021. RCTs that recruited patients with active UC and treated them with FMT, a placebo or a suitable comparator were included in the meta-analysis. PICOS: Patients, active UC; Intervention, FMT; Control, placebo or a suitable comparator; Outcomes, remission rate; Studies, RCTs. The risk of bias assessment was performed with Revised Cochrane risk-of-bias tool (version 2). Meta-analyses of risk ratios (RRs) were performed to estimate the differences in remission rates and the risk of serious adverse events (SAEs) between the FMT-treated and control patients.<br><br>RESULTS: A total of 9 RCTs comprising 425 UC patients (213 FMT and 212 control) were included in the meta-analysis. The risk of bias was low in these RCTs. Clinical remission was observed in 86 of the 213 patients in the FMT groups and 47 of the 212 patients in the control groups [RR: 1.84; 95% confidence interval (CI): 1.37, 2.47; P<0.0001]. Clinical remission was better when the FMT delivery route was via the lower gut, the FMT dose was >300 grams, and the fecal specimen from multiple donors. Endoscopic remission (observed in 7 RCTs) was achieved in 33 of the 195 FMT-treated patients compared to 17 of the 194 control patients (RR: 1.94; 95% CI: 1.14, 3.31; P=0.01). SAEs were reported in 22 of the 213 FMT-treated patients but only 11 of the 212 control patients (RR: 2.05; 95% CI: 1.03, 4.09; P=0.04).<br><br>DISCUSSION: FMT is an effective treatment for patients with active UC. Significantly higher clinical and endoscopic remission rates are observed with FMT than with control treatments. However, FMT may cause a significantly higher incidence of SAEs than control treatments. Future studies should delineate the effects of donor selection, dosage, delivery route, and antibiotic pretreatment and should evaluate the safety profile of FMT.}, }
@article {pmid35964945, year = {2022}, author = {Kapoor, B and Gulati, M and Rani, P and Gupta, R}, title = {Psoriasis: Interplay between dysbiosis and host immune system.}, journal = {Autoimmunity reviews}, volume = {21}, number = {11}, pages = {103169}, doi = {10.1016/j.autrev.2022.103169}, pmid = {35964945}, issn = {1873-0183}, mesh = {Humans ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Prebiotics ; *Probiotics/therapeutic use ; *Psoriasis ; Immune System ; Bacteria ; }, abstract = {With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of both gut and skin microbiota in the pathogenesis of psoriasis. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts, have been identified as possible triggers for recurrent episodes of psoriasis. Mechanistically, gut dysbiosis leads to "leaky gut syndrome" via disruption of epithelial bilayer, thereby, resulting in translocation of bacteria and other endotoxins to systemic circulation, which in turn, results in inflammatory response. Similarly, skin dysbiosis disrupts the cutaneous homeostasis, leading to invasion of bacteria and other pathogens to deeper layers of skin or even systemic circulation further enhanced by injury caused by pruritus-induced scratching, and elicit innate and adaptive inflammation. The present review explores the correlation of both skin and gut microbiota dysbiosis with psoriasis. Also, the studies highlighting the potential of bacteriotherapeutic approaches including probiotics, prebiotics, metabiotics, and fecal microbiota transplantation for the management of psoriasis have been discussed.}, }
@article {pmid35963468, year = {2022}, author = {Zain, NMM and Ter Linden, D and Lilley, AK and Royall, PG and Tsoka, S and Bruce, KD and Mason, AJ and Hatton, GB and Allen, E and Goldenberg, SD and Forbes, B}, title = {Design and manufacture of a lyophilised faecal microbiota capsule formulation to GMP standards.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {350}, number = {}, pages = {324-331}, doi = {10.1016/j.jconrel.2022.08.012}, pmid = {35963468}, issn = {1873-4995}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Feces ; Humans ; *Microbiota ; Powders ; Recurrence ; Treatment Outcome ; Trehalose ; }, abstract = {Faecal microbiota transplant (FMT) is an established and effective treatment for recurrent Clostridioides difficile infection (CDI) and has many other potential clinical applications. However, preparation and quality of FMT is poorly standardised and clinical studies are hampered by a lack of well-defined FMT formulations that meet regulatory standards for medicines. As an alternative to FMT suspensions for administration by nasojejunal tube or colonoscopy, which is invasive and disliked by many patients, this study aimed to develop a well-controlled, standardised method for manufacture of lyophilised FMT capsules and to provide stability data allowing storage for extended time periods. Faecal donations were collected from healthy, pre-screened individuals, homogenised, filtered and centrifuged to remove dietary matter. The suspension was centrifuged to pellet bacteria, which were resuspended with trehalose and lyophilised to produce a powder which was filled into 5 enteric-coated capsules (size 0). Live-dead bacterial cell quantitative PCR assay showed <10 fold viable bacterial load reduction through the manufacturing process. No significant loss of viable bacterial load was observed after storage at -80 °C for 36 weeks (p = 0.24, n = 5). Initial clinical experience demonstrated that the capsules produced clinical cure in patients with CDI with no adverse events reported (n = 7). We provide the first report of a detailed manufacturing protocol and specification for an encapsulated lyophilised formulation of FMT. As clinical trials into intestinal microbiota interventions proceed, it is important to use a well-controlled investigational medicinal product in the studies so that any beneficial results can be replicated in clinical practice.}, }
@article {pmid35962694, year = {2022}, author = {Dobrek, &#x141;}, title = {POTENTIAL THERAPEUTIC OPTIONS TARGETING THE GUT DYSBIOSIS IN CHRONIC KIDNEY DISEASE.}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {75}, number = {7}, pages = {1757-1764}, doi = {10.36740/WLek202207127}, pmid = {35962694}, issn = {0043-5147}, mesh = {Dysbiosis/complications/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Humans ; Prebiotics ; *Probiotics/therapeutic use ; *Renal Insufficiency, Chronic/complications/drug therapy/metabolism ; }, abstract = {The gut microbiota plays an important physiological role in controlling not only the function of the gastrointestinal tract, but also in maintaining systemic homeostasis. Quantitative and /or qualitative disturbances of the gut microbiota (dysbiosis) are an important element in the complex pathogenesis of many diseases, including chronic kidney disease (CKD). In the disease, the mutual interactions between disturbed gut microbiota and the progression of CKD (pathophysiological "kidney-gut axis") have been demonstrated. The kidney failure causes water and nitrogen waste retention which leads to disturbances of motility, secretion and absorption in the gastrointestinal tract. These abnormalities contribute to the development of gut dysbiosis, accompanied by overproduction of toxic bacterial metabolites, with their translocation to the peripheral blood and development of endotoxemia. As a consequence, chronic kidney "low-grade" inflammation and oxidative stress develop, with further deterioration of kidney function in the mechanism of the "vicious cycle" of the kidney-gut axis. Considering the key role of gut dysbiosis and the kidney-gut axis, the attempts to restore the gut eubiosis seem to have an important role in the treatment of CKD and may be even regarded as a form of causal therapeutic intervention. The paper briefly discusses the basics of the pathophysiological kidney-gut axis in CKD and potential methods of modulating the abnormal gut microbiota in this disease, including the use of probiotic or prebiotic preparations, agents that absorb bacterial-derived toxins in the intestinal lumen, fecal microbiota transplantation and drugs used so far for other indications (acarbose, meclofenamate, lubiprostone).}, }
@article {pmid35962454, year = {2022}, author = {Huang, C and Huang, Z and Ding, L and Fu, Y and Fan, J and Mei, Q and Lou, L and Wang, J and Yin, N and Lu, Y and Guo, S and Zeng, Y}, title = {Fecal microbiota transplantation versus glucocorticoids for the induction of remission in mild to moderate ulcerative colitis.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {354}, pmid = {35962454}, issn = {1479-5876}, mesh = {*Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Glucocorticoids/therapeutic use ; Humans ; Interleukin-10 ; Interleukin-6 ; Prospective Studies ; Remission Induction ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; }, abstract = {OBJECTIVE: To compare efficacy and safety of fecal microbiota transplantation (FMT) with glucocorticoid as induction therapy in ulcerative colitis (UC).<br><br>METHODS: The patients with active mild to moderate UC were recruited into the single-center, prospective cohort study. The patients were treated with either FMT (FMT group) or glucocorticoids (GCs group). Patients received FMT administration for 3&#xa0;days. The primary outcome was clinical and endoscopic remission at week 12. Inflammatory parameters were assessed by routine blood tests. Safety was assessed by adverse events recorded. The serum levels of TNF-&#x3b1;, IFN-&#x3b3;, IL-1&#x3b2;, IL-4, IL-5, IL-6, IL-10 IL-8, IL-12p70, IL-13, IL-17A and IL-23 following FMT were measured by Luminex multiplex assay.<br><br>RESULTS: Of the 122 patients, 62 patients were treated with FMT and 60 with glucocorticoids. 34 patients in FMT group (54.8%) and 29 in GCs group (48.3%) reached the primary outcome (p&#x2009;=&#x2009;0.30). The incidence of adverse events in GCs group (35/60, 58.3%) was significantly higher than that in FMT group (14/62, 22.6%) and two serious adverse events were observed following GCs. Patients in FMT group were stratified into responders (RE) and non-responders (NR) groups. The level of TNF-&#x3b1; and IL-6 decreased significantly in RE group, while IL-10 decreased significantly in NR group.<br><br>CONCLUSION: FMT therapy was as effective as glucocorticoids to induce remission in active mild to moderate UC, accompanied by fewer adverse events. The modification of serum TNF-&#x3b1;, IL-6 and IL-10 might be related to the efficacy of FMT in UC. Trial registration This study was registered with ClinicalTrials.gov (NCT02435160). Registered on 6 April, 2015. https://clinicaltrials.gov/ct2/results?cond=&amp;term=NCT02435160&amp;cntry=&amp;state=&amp;city=&amp;dist=.}, }
@article {pmid35953888, year = {2022}, author = {Simpson, JB and Sekela, JJ and Graboski, AL and Borlandelli, VB and Bivins, MM and Barker, NK and Sorgen, AA and Mordant, AL and Johnson, RL and Bhatt, AP and Fodor, AA and Herring, LE and Overkleeft, H and Lee, JR and Redinbo, MR}, title = {Metagenomics combined with activity-based proteomics point to gut bacterial enzymes that reactivate mycophenolate.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2107289}, pmid = {35953888}, issn = {1949-0984}, support = {T32 GM135095/GM/NIGMS NIH HHS/United States ; K23 AI124464/AI/NIAID NIH HHS/United States ; T32 DK007750/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 GM137286/GM/NIGMS NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; }, mesh = {Flavin Mononucleotide ; *Gastrointestinal Microbiome/physiology ; Glucuronides ; Humans ; Immunosuppressive Agents ; Mycophenolic Acid/therapeutic use ; Proteomics ; }, abstract = {Mycophenolate mofetil (MMF) is an important immunosuppressant prodrug prescribed to prevent organ transplant rejection and to treat autoimmune diseases. MMF usage, however, is limited by severe gastrointestinal toxicity that is observed in approximately 45% of MMF recipients. The active form of the drug, mycophenolic acid (MPA), undergoes extensive enterohepatic recirculation by bacterial β-glucuronidase (GUS) enzymes, which reactivate MPA from mycophenolate glucuronide (MPAG) within the gastrointestinal tract. GUS enzymes demonstrate distinct substrate preferences based on their structural features, and gut microbial GUS enzymes that reactivate MPA have not been identified. Here, we compare the fecal microbiomes of transplant recipients receiving MMF to healthy individuals using shotgun metagenomic sequencing. We find that neither microbial composition nor the presence of specific structural classes of GUS genes are sufficient to explain the differences in MPA reactivation measured between fecal samples from the two cohorts. We next employed a GUS-specific activity-based chemical probe and targeted metaproteomics to identify and quantify the GUS proteins present in the human fecal samples. The identification of specific GUS enzymes was improved by using the metagenomics data collected from the fecal samples. We found that the presence of GUS enzymes that bind the flavin mononucleotide (FMN) is significantly correlated with efficient MPA reactivation. Furthermore, structural analysis identified motifs unique to these FMN-binding GUS enzymes that provide molecular support for their ability to process this drug glucuronide. These results indicate that FMN-binding GUS enzymes may be responsible for reactivation of MPA and could be a driving force behind MPA-induced GI toxicity.}, }
@article {pmid35950704, year = {2022}, author = {Jin, J and Gao, L and Zou, X and Zhang, Y and Zheng, Z and Zhang, X and Li, J and Tian, Z and Wang, X and Gu, J and Zhang, C and Wu, T and Wang, Z and Zhang, Q}, title = {Gut Dysbiosis Promotes Preeclampsia by Regulating Macrophages and Trophoblasts.}, journal = {Circulation research}, volume = {131}, number = {6}, pages = {492-506}, doi = {10.1161/CIRCRESAHA.122.320771}, pmid = {35950704}, issn = {1524-4571}, mesh = {Animals ; Dysbiosis/microbiology ; Fatty Acids, Volatile/metabolism ; Female ; Humans ; *Hypertension ; Inflammation/complications ; Macrophages/metabolism ; Placenta/metabolism ; *Pre-Eclampsia ; Pregnancy ; Propionates ; RNA, Ribosomal, 16S/genetics ; Rats ; Trophoblasts/metabolism ; }, abstract = {BACKGROUND: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and is characterized by hypertension, inflammation, and placental dysfunction. Gut microbiota plays key roles in inflammation and hypertension. However, its roles and mechanisms in preeclampsia have not been fully elucidated.<br><br>METHODS: 16S rRNA gene sequencing and targeted metabolomics were conducted on stool samples from 92 preeclamptic patients and 86 normal late-pregnant women. Then, fecal microbiota transplantation and in vitro and in vivo functional experiments were performed to explore the roles and mechanisms of gut microbiota in preeclampsia development.<br><br>RESULTS: We revealed the gut microbiota dysbiosis in preeclamptic patients, including significant reductions in short-chain fatty acid-producing bacteria and short-chain fatty acids. The gut microbiota of preeclamptic patients significantly exacerbated pathologies and symptoms of preeclamptic rats, whereas the gut microbiota of healthy pregnant women had significant protective effects. Akkermansia muciniphila, propionate, or butyrate significantly alleviated the symptoms of preeclamptic rats. Mechanistically, they significantly promoted autophagy and M2 polarization of macrophages in placental bed, thereby suppressing inflammation. Propionate also significantly promoted trophoblast invasion, thereby improved spiral arterial remodeling. Additionally, we identified a marker set consisting of Akkermansia, Oscillibacter, and short-chain fatty acids that could accurately diagnose preeclampsia.<br><br>CONCLUSIONS: Our study revealed that gut microbiota dysbiosis is an important etiology of preeclampsia. Gut microbiota and their active metabolites have great potential for the treatment and diagnosis of preeclampsia. Our findings enrich the gut-placenta axis theory and contribute to the development of microecological products for preeclampsia.}, }
@article {pmid35949981, year = {2022}, author = {Xie, C and Teng, J and Wang, X and Xu, B and Niu, Y and Ma, L and Yan, X}, title = {Multi-omics analysis reveals gut microbiota-induced intramuscular fat deposition via regulating expression of lipogenesis-associated genes.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {9}, number = {}, pages = {84-99}, pmid = {35949981}, issn = {2405-6383}, abstract = {The gut microbiome has great effects on the digestion, absorption, and metabolism of lipids. However, the microbiota composition that can alter the fat deposition and the meat quality of pigs remains unclear. Here, we used Laiwu (LW) pigs (a native Chinese breed with higher intramuscular fat) compared with commercial crossbreed Duroc × (Landrace × Yorkshire) (DLY) pigs to investigate the effects of microbiota on meat quality, especially in intramuscular fat content. A total of 32 DLY piglets were randomly allotted to 4 groups and transplanted with fecal microbiota from healthy LW pigs. The results indicated that the high dose of fecal microbiota transplantation (HFMT) selectively enhanced fat deposition in longissimus dorsi (P < 0.05) but decreased backfat thickness (P < 0.05) compared with control group. HFMT significantly altered meat color and increased feed conversation ratio (P < 0.05). Furthermore, the multi-omics analysis revealed that Bacteroides uniformis, Sphaerochaeta globosa, Hydrogenoanaerobacterium saccharovorans, and Pyramidobacter piscolens are the core species which can regulate lipid deposition. A total of 140 male SPF C57BL/6j mice were randomly allotted into 7 groups and administrated with these 4 microbes alone or consortium to validate the relationships between microbiota and lipid deposition. Inoculating the bacterial consortium into mice increased intramuscular fat content (P < 0.05) compared with control mice. Increased expressions of lipogenesis-associated genes including cluster of differentiation 36 (Cd36), diacylglycerol O-acyltransferase 2 (Dgat2), and fatty acid synthase (FASN) were observed in skeletal muscle in the mice with mixed bacteria compared with control mice. Together, our results suggest that the gut microbiota may play an important role in regulating the lipid deposition in the muscle of pigs and mice.}, }
@article {pmid35949351, year = {2022}, author = {Zheng, L and Ji, YY and Wen, XL and Duan, SL}, title = {Fecal microbiota transplantation in the metabolic diseases: Current status and perspectives.}, journal = {World journal of gastroenterology}, volume = {28}, number = {23}, pages = {2546-2560}, pmid = {35949351}, issn = {2219-2840}, mesh = {*Clostridium Infections/microbiology ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces/microbiology ; Humans ; *Metabolic Diseases/therapy ; Treatment Outcome ; }, abstract = {With the development of microbiology and metabolomics, the relationship between the intestinal microbiome and intestinal diseases has been revealed. Fecal microbiota transplantation (FMT), as a new treatment method, can affect the course of many chronic diseases such as metabolic syndrome, malignant tumor, autoimmune disease and nervous system disease. Although the mechanism of action of FMT is now well understood, there is some controversy in metabolic diseases, so its clinical application may be limited. Microflora transplantation is recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection, and has been gradually promoted for the treatment of other intestinal and extraintestinal diseases. However, the initial results are varied, suggesting that the heterogeneity of the donor stools may affect the efficacy of FMT. The success of FMT depends on the microbial diversity and composition of donor feces. Therefore, clinical trials may fail due to the selection of ineffective donors, and not to faulty indication selection for FMT. A new understanding is that FMT not only improves insulin sensitivity, but may also alter the natural course of type 1 diabetes by modulating autoimmunity. In this review, we focus on the main mechanisms and deficiencies of FMT, and explore the optimal design of FMT research, especially in the field of cardiometabolic diseases.}, }
@article {pmid35947590, year = {2022}, author = {Koopman, N and van Leeuwen, P and Brul, S and Seppen, J}, title = {History of fecal transplantation; camel feces contains limited amounts of Bacillus subtilis spores and likely has no traditional role in the treatment of dysentery.}, journal = {PloS one}, volume = {17}, number = {8}, pages = {e0272607}, pmid = {35947590}, issn = {1932-6203}, mesh = {Animals ; *Bacillus subtilis ; Camelus ; *Dysentery ; Fecal Microbiota Transplantation ; Feces ; Humans ; Spores, Bacterial ; }, abstract = {INTRODUCTION: A widely cited story on the origins of fecal transplantation suggests that German soldiers in North Africa used camel feces containing Bacillus subtilis to treat dysentery in World War 2. We investigated if this story is accurate and if there is sufficient Bacillus subtilis in camel feces to be potentially therapeutic.<br><br>METHODS AND RESULTS: A literature analysis shows that all references to the story are based on a single review paper that mentions the use of camel feces in passing and only provides indirect evidence for this claim. An extensive literature search failed to find independent evidence that camel feces has traditionally been used in the treatment of dysentery in North Africa. With 16S sequence analysis we did not detect Bacillus subtilis in feces from two different Egyptian camels. Using a more sensitive culture-based assay we could detect low amounts of Bacillus subtilis spores in these fecal samples, with comparable concentrations to those present in human feces and soil.<br><br>CONCLUSIONS: Because we could not find evidence for the use of camel feces in the treatment of diarrhea and because we show that only low amounts of Bacillus subtilis spores are present in camel feces, we conclude that the use of camel feces should no longer be mentioned in the context of origins of fecal transplantation.}, }
@article {pmid35943661, year = {2022}, author = {Ma, W and Drew, DA and Staller, K}, title = {The Gut Microbiome and Colonic Motility Disorders: A Practical Framework for the Gastroenterologist.}, journal = {Current gastroenterology reports}, volume = {24}, number = {10}, pages = {115-126}, pmid = {35943661}, issn = {1534-312X}, support = {K01 DK120742/DK/NIDDK NIH HHS/United States ; K23 DK120945/DK/NIDDK NIH HHS/United States ; K01DK120742/DK/NIDDK NIH HHS/United States ; K23DK120945/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastroenterologists ; *Gastrointestinal Microbiome/physiology ; *Irritable Bowel Syndrome/etiology/therapy ; Constipation ; Diarrhea ; Metagenome ; }, abstract = {PURPOSE OF REVIEW: Colonic motility disorders may be influenced by the gut microbiota, which plays a role in modulating sensory and motor function. However, existing data are inconsistent, possibly due to complex disease pathophysiology, fluctuation in symptoms, and difficulty characterizing high-resolution taxonomic composition and function of the gut microbiome.<br><br>RECENT FINDINGS: Increasingly, human studies have reported associations between gut microbiome features and colonic motility disorders, such as irritable bowel syndrome and constipation. Several microbial metabolites have been identified as regulators of colonic motility in animal models. Modulation of the gut microbiota via dietary intervention, probiotics, and fecal microbiota transplant is a promising avenue for treatment for these diseases. An integration of longitudinal multi-omics data will facilitate further understanding of the causal effects of dysbiosis on disease. Further understanding of the microbiome-driven mechanisms underlying colonic motility disorders may be leveraged to develop personalized, microbiota-based approaches for disease prevention and treatment.}, }
@article {pmid35935787, year = {2022}, author = {Jung, JH and Kim, SE and Suk, KT and Kim, DJ}, title = {Gut microbiota-modulating agents in alcoholic liver disease: Links between host metabolism and gut microbiota.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {913842}, pmid = {35935787}, issn = {2296-858X}, abstract = {Alcoholic liver disease (ALD) involves a wide spectrum of diseases, including asymptomatic hepatic steatosis, alcoholic hepatitis, hepatic fibrosis, and cirrhosis, which leads to morbidity and mortality and is responsible for 0.9% of global deaths. Alcohol consumption induces bacterial translocation and alteration of the gut microbiota composition. These changes in gut microbiota aggravate hepatic inflammation and fibrosis. Alteration of the gut microbiota leads to a weakened gut barrier and changes host immunity and metabolic function, especially related to bile acid metabolism. Modulation and treatment for the gut microbiota in ALD has been studied using probiotics, prebiotics, synbiotics, and fecal microbial transplantation with meaningful results. In this review, we focused on the interaction between alcohol and gut dysbiosis in ALD. Additionally, treatment approaches for gut dysbiosis, such as abstinence, diet, pro-, pre-, and synbiotics, antibiotics, and fecal microbial transplantation, are covered here under ALD. However, further research through human clinical trials is warranted to evaluate the appropriate gut microbiota-modulating agents for each condition related to ALD.}, }
@article {pmid35934088, year = {2022}, author = {Zhu, X and Zhang, Z and Yang, X and Qi, L and Guo, Y and Tang, X and Xie, Y and Chen, D}, title = {RETRACTED: Improvement of extraction from Hericium erinaceus on the gut-brain axis in AD-like mice.}, journal = {Brain research}, volume = {1793}, number = {}, pages = {148038}, doi = {10.1016/j.brainres.2022.148038}, pmid = {35934088}, issn = {1872-6240}, mesh = {*Alzheimer Disease/pathology ; Animals ; Brain-Gut Axis ; Hericium ; Inflammation ; Mice ; RNA, Ribosomal, 16S ; }, abstract = {This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the lead author, Dr. Diling Chen. Dr. Chen alerted the Editor-in-Chief that data previously published in Aging (Albany NY). 2020 Jan 6; 12:260-287 https://doi.org/10.18632/aging.102614 were accidently reused in the above-referenced Brain Research article. Dr. Chen is a co-author on both articles. The reused content pertains to the fecal transplantation data of the model group, represented by Figure 2 in the Aging article and Figure 5 in the Brain Research article. Dr. Chen did not carefully check the data published by the team before the final submission, resulting in repeated use. The lead author states further that it was an honest mistake, and the team had no intention to plagiarize previously published material. All authors were notified and all are in agreement with the retraction. The authors apologize to the scientific community for any inconvenience or challenges resulting from the publication and retraction of this article.}, }
@article {pmid35934034, year = {2022}, author = {Liu, Y and Kang, W and Liu, S and Li, J and Liu, J and Chen, X and Gan, F and Huang, K}, title = {Gut microbiota-bile acid-intestinal Farnesoid X receptor signaling axis orchestrates cadmium-induced liver injury.}, journal = {The Science of the total environment}, volume = {849}, number = {}, pages = {157861}, doi = {10.1016/j.scitotenv.2022.157861}, pmid = {35934034}, issn = {1879-1026}, mesh = {Animals ; Anti-Bacterial Agents/metabolism ; Bile Acids and Salts/metabolism ; Cadmium/metabolism/toxicity ; *Chemical and Drug Induced Liver Injury, Chronic/metabolism ; Dysbiosis/chemically induced ; *Environmental Pollutants/metabolism ; *Gastrointestinal Microbiome/physiology ; Inflammation ; Intestines ; Liver/metabolism ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; Receptors, Cytoplasmic and Nuclear/metabolism ; }, abstract = {Cadmium (Cd) is a widely prevalent environmental pollutant that accumulates in the liver and induces liver injury. The mechanism of Cd-induced liver injury remains elusive. Our study aimed to clarify the mechanism by which changes in the gut microbiota contribute to Cd-induced liver injury. Here, a murine model of liver injury induced by chronic Cd exposure was used. Liver injury was assessed by biochemistry and histopathology. Expression profiles of genes involved in bile acid (BA) homeostasis, inflammation and injury were assessed via Realtime-PCR and Western-blot. 16S rRNA gene sequencing and mass spectrometry-based metabolomics were used to investigate changes in the gut microbiota and its metabolites in the regulation of Cd-induced liver injury. Here, we showed that Cd exposure induced hepatic ductular proliferation, hepatocellular damage and inflammatory infiltration in mice. Cd exposure induced gut microbiota dysbiosis and reduced the fecal bile salt hydrolase activity leading to an increase of tauro-β-muricholic acid levels in the intestine. Cd exposure decreased intestine FXR/FGF-15 signaling and promoted hepatic BA synthesis. Furthermore, the mice receiving fecal microbiota transplantation from Cd-treated mice showed reduced intestinal FXR/FGF-15 signaling, increased hepatic BA synthesis, and liver injury. However, the depletion of the commensal microbiota by antibiotics failed to change these indices in Cd-treated mice. Finally, the administration of the intestine-restricted FXR agonist fexaramine attenuated the liver injury, improved the intestinal barrier, and decreased hepatic BA synthesis in the Cd-treated mice. Our study identified a new mechanism of Cd-induced liver injury. Cd-induced gut microbiota dysbiosis, decreased feces BSH activity, and increased intestinal T-βMCA levels led to an inhibition of intestinal FXR/FGF-15 signaling and an increase in hepatic BA synthesis, ultimately facilitating the development of hepatic ductular proliferation, inflammation, and injury in mice. This study expands our understanding of the health hazards caused by environmental Cd pollution.}, }
@article {pmid35933808, year = {2022}, author = {Huang, J and Liu, W and Kang, W and He, Y and Yang, R and Mou, X and Zhao, W}, title = {Effects of microbiota on anticancer drugs: Current knowledge and potential applications.}, journal = {EBioMedicine}, volume = {83}, number = {}, pages = {104197}, pmid = {35933808}, issn = {2352-3964}, mesh = {*Antineoplastic Agents/pharmacology/therapeutic use ; Biomarkers ; Fecal Microbiota Transplantation ; Humans ; Immune Checkpoint Inhibitors ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {Over the last decade, mounting evidence has revealed the key roles of gut microbiota in modulating the efficacy and toxicity of anticancer drugs, via mechanisms such as immunomodulation and microbial enzymatic degradation. As such, human microbiota presents as an exciting prospect for developing biomarkers for predicting treatment outcomes and interventional approaches for improving therapeutic effects. In this review, we analyze the current knowledge of the interplays among gut microorganisms, host responses and anticancer therapies (including cytotoxic chemotherapy and targeted therapy), with an emphasis on the immunomodulation function of microbiota which facilitates the efficacy of immune checkpoint inhibitors. Moreover, we propose several microbiota-modulating strategies including fecal microbiota transplantation and probiotics, which can be pursued to optimize the use and development of anticancer treatments. We anticipate that future clinical and preclinical studies will highlight the significance of human microbiome as a promising target towards precision medicine in cancer therapies. FUNDING: National Key Research and Development Program of China (2020YFA0907800), Shenzhen Science and Technology Innovation Program (KQTD20200820145822023) and National Natural Science Foundation of China (31900056 and 32000096).}, }
@article {pmid35932662, year = {2022}, author = {Chen, Y and Lin, J and Xiao, L and Zhang, X and Zhao, L and Wang, M and Li, L}, title = {Gut microbiota in systemic lupus erythematosus: A fuse and a solution.}, journal = {Journal of autoimmunity}, volume = {132}, number = {}, pages = {102867}, doi = {10.1016/j.jaut.2022.102867}, pmid = {35932662}, issn = {1095-9157}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Lupus Erythematosus, Systemic/therapy ; Fecal Microbiota Transplantation ; Autoantibodies ; Inflammation ; }, abstract = {Gut commensals help shape and mold host immune system and deeply influence human health. The disease spectrum of mankind that gut microbiome may associate with is ever-growing, but the mechanisms are still enigmas. Characterized by loss of self-tolerance and sustained self-attack, systemic lupus erythematosus (SLE) is labeled with chronic inflammation, production of autoantibodies and multisystem injury, which so far are mostly incurable. Gut microbiota and their metabolites, now known as important environmental triggers of local/systemic immune responses, have been proposed to be involved in SLE development and progression probably through the following mechanisms: translocation beyond their niches; molecular mimicry to cross-activate immune response targeting self-antigens; epitope spreading to expand autoantibodies spectrum; and bystander activation to promote systemic inflammation. Gut microbiota which varies between individuals may also influence the metabolism and bio-transformation of disease-modifying anti-rheumatic drugs, thus associated with the efficacy and toxicity of these drugs, adding another explanation for heterogenic therapeutic responses. Modulation of gut microbiota via diet, probiotics/prebiotics, antibiotics/phages, fecal microbiota transplantation, or helminth to restore immune tolerance and homeostasis is expected to be a promising neoadjuvant therapy for SLE. We reviewed the advances in this territory and discussed the application prospect of modulating gut microbiota in controlling SLE.}, }
@article {pmid35931825, year = {2022}, author = {Correale, J and Hohlfeld, R and Baranzini, SE}, title = {The role of the gut microbiota in multiple sclerosis.}, journal = {Nature reviews. Neurology}, volume = {18}, number = {9}, pages = {544-558}, pmid = {35931825}, issn = {1759-4766}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; Immune System ; Mice ; *Microbiota ; *Multiple Sclerosis/therapy ; *Probiotics/therapeutic use ; }, abstract = {During the past decade, research has revealed that the vast community of micro-organisms that inhabit the gut - known as the gut microbiota - is intricately linked to human health and disease, partly as a result of its influence on systemic immune responses. Accumulating evidence demonstrates that these effects on immune function are important in neuroinflammatory diseases, such as multiple sclerosis (MS), and that modulation of the microbiome could be therapeutically beneficial in these conditions. In this Review, we examine the influence that the gut microbiota have on immune function via modulation of serotonin production in the gut and through complex interactions with components of the immune system, such as T cells and B cells. We then present evidence from studies in mice and humans that these effects of the gut microbiota on the immune system are important in the development and course of MS. We also consider how strategies for manipulating the composition of the gut microbiota could be used to influence disease-related immune dysfunction and form the basis of a new class of therapeutics. The strategies discussed include the use of probiotics, supplementation with bacterial metabolites, transplantation of faecal matter or defined microbial communities, and dietary intervention. Carefully designed studies with large human cohorts will be required to gain a full understanding of the microbiome changes involved in MS and to develop therapeutic strategies that target these changes.}, }
@article {pmid35931074, year = {2022}, author = {Podlesny, D and Durdevic, M and Paramsothy, S and Kaakoush, NO and Högenauer, C and Gorkiewicz, G and Walter, J and Fricke, WF}, title = {Identification of clinical and ecological determinants of strain engraftment after fecal microbiota transplantation using metagenomics.}, journal = {Cell reports. Medicine}, volume = {3}, number = {8}, pages = {100711}, pmid = {35931074}, issn = {2666-3791}, mesh = {*Clostridium Infections/therapy ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Humans ; Metagenomics ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising therapeutic approach for microbiota-associated pathologies, but our understanding of the post-FMT microbiome assembly process and its ecological and clinical determinants is incomplete. Here we perform a comprehensive fecal metagenome analysis of 14 FMT trials, involving five pathologies and >250 individuals, and determine the origins of strains in patients after FMT. Independently of the underlying clinical condition, conspecific coexistence of donor and recipient strains after FMT is uncommon and donor strain engraftment is strongly positively correlated with pre-FMT recipient microbiota dysbiosis. Donor strain engraftment was enhanced through antibiotic pretreatment and bowel lavage and dependent on donor and recipient ɑ-diversity; strains from relatively abundant species were more likely and from predicted oral, oxygen-tolerant, and gram-positive species less likely to engraft. We introduce a general mechanistic framework for post-FMT microbiome assembly in alignment with ecological theory, which can guide development of optimized, more targeted, and personalized FMT therapies.}, }
@article {pmid35928832, year = {2022}, author = {Zhu, W and Hong, Y and Li, Y and Li, Y and Zhong, J and He, X and Zheng, N and Sheng, L and Li, H}, title = {Microbial and Transcriptomic Profiling Reveals Diet-Related Alterations of Metabolism in Metabolic Disordered Mice.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {923377}, pmid = {35928832}, issn = {2296-861X}, abstract = {Metabolic disorders are the prelude of metabolic diseases, which are mainly due to the high-energy intake and genetic contribution. High-fat diet (HFD) or high-sucrose diet is widely used for inducing metabolic disorders characterized by increased body weight, insulin resistance, hepatic steatosis, and alteration of gut microbiome. However, the triangle relationship among diets, gut microbiome, and host metabolism is poorly understood. In our study, we investigated the dynamic changes in gut microbiota, and host metabolism in mice that were fed with either chow diet, HFD, or chow diet with 30% sucrose in drinking water (HSD) for continued 12 weeks. The gut microbiota was analyzed with 16S rDNA sequencing on feces. Hepatic gene expression profile was tested with transcriptomics analysis on liver tissue. The host metabolism was evaluated by measuring body weight, insulin sensitivity, serum lipids, and expression of proteins involved in lipid metabolism of liver. The results showed that HFD feeding affected body weight, insulin resistance, and hepatic steatosis more significantly than HSD feeding. 16S rRNA gene sequencing showed that HFD rapidly and steadily suppressed species richness, altered microbiota structure and function, and increased the abundance of bacteria responsible for fatty acid metabolism and inflammatory signaling. In contrast, HSD had minor impact on the overall bacteria structure or function but activated microbial bile acid biosynthesis. Fecal microbiota transplantation suggested that some metabolic changes induced by HFD or HSD feeding were transferrable, especially in the weight of white adipose tissue and hepatic triglyceride level that were consistent with the phenotypes in donor mice. Moreover, transcriptomic results showed that HFD feeding significantly inhibited fatty acid degradation and increase inflammation, while HSD increased hepatic de novo lipogenesis and inhibited primary bile acid synthesis alternative pathway. In general, our study revealed the dynamic and diversified impacts of HFD and HSD on gut microbiota and host metabolism.}, }
@article {pmid35928828, year = {2022}, author = {Yang, Z and Liu, X and Wu, Y and Peng, J and Wei, H}, title = {Effect of the Microbiome on Intestinal Innate Immune Development in Early Life and the Potential Strategy of Early Intervention.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {936300}, pmid = {35928828}, issn = {1664-3224}, mesh = {Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunity, Innate ; Infant, Newborn ; Mammals ; *Microbiota ; *Probiotics ; }, abstract = {Early life is a vital period for mammals to be colonized with the microbiome, which profoundly influences the development of the intestinal immune function. For neonates to resist pathogen infection and avoid gastrointestinal illness, the intestinal innate immune system is critical. Thus, this review summarizes the development of the intestinal microbiome and the intestinal innate immune barrier, including the intestinal epithelium and immune cells from the fetal to the weaning period. Moreover, the impact of the intestinal microbiome on innate immune development and the two main way of early-life intervention including probiotics and fecal microbiota transplantation (FMT) also are discussed in this review. We hope to highlight the crosstalk between early microbial colonization and intestinal innate immunity development and offer some information for early intervention.}, }
@article {pmid35926806, year = {2022}, author = {He, N and Shen, G and Jin, X and Li, H and Wang, J and Xu, L and Chen, J and Cao, X and Fu, C and Shi, D and Song, X and Liu, S and Li, Y and Zhao, T and Li, J and Zhong, J and Shen, Y and Zheng, M and Chen, YY and Wang, LL}, title = {Resveratrol suppresses microglial activation and promotes functional recovery of traumatic spinal cord via improving intestinal microbiota.}, journal = {Pharmacological research}, volume = {183}, number = {}, pages = {106377}, doi = {10.1016/j.phrs.2022.106377}, pmid = {35926806}, issn = {1096-1186}, mesh = {Animals ; Anti-Inflammatory Agents/pharmacology ; Butyrates/pharmacology ; Dysbiosis ; Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Mice ; Microglia/metabolism ; RNA, Ribosomal, 16S ; Resveratrol/pharmacology/therapeutic use ; *Spinal Cord Injuries/drug therapy ; }, abstract = {Spinal cord injury (SCI) can change the intestinal microbiota pattern and corresponding metabolites, which in turn affect the prognosis of SCI. Among many metabolites, short-chain fatty acids (SCFAs) are critical for neurological recovery after SCI. Recent research has shown that resveratrol exerts anti-inflammatory properties. But it is unknown if the anti-inflammatory properties of resveratrol are associated with intestinal microbiota and metabolites. We thus investigate the alteration in gut microbiota and the consequent change of SCFAs following resveratrol treatment. The SCI mouse models with retention of gut microbiota (donor) and depletion of gut microbiota (recipient) were established. Fecal microbiota transplantation from donors to recipients was performed with intragastrical administration. Spinal cord tissues of mice were examined by H&amp;E, Nissl, and immunofluorescence stainings. The expressions of the inflammatory profile were examined by qPCR and cytometric bead array. Fecal samples of mice were collected and analyzed with 16S rRNA sequencing. The results showed that resveratrol inhibited the microglial activation and promoted the functional recovery of SCI. The analysis of intestinal microbiota and metabolites indicated that SCI caused dysbiosis and the decrease in butyrate, while resveratrol restored microbiota pattern, reversed intestinal dysbiosis, and increased the concentration of butyrate. Both fecal supernatants from resveratrol-treated donors and butyrate suppressed the expression of pro-inflammatory genes in BV2 microglia. Our result demonstrated that fecal microbiota transplantation from resveratrol-treated donors had beneficial effects on the functional recovery of SCI. One mechanism of resveratrol effects was to restore the disrupted gut microbiota and butyrate.}, }
@article {pmid35926310, year = {2022}, author = {Tian, B and Zhang, Y and Deng, C and Guo, C}, title = {Efficacy of Probiotic Consortium Transplantation on Experimental Necrotizing Enterocolitis.}, journal = {The Journal of surgical research}, volume = {279}, number = {}, pages = {598-610}, doi = {10.1016/j.jss.2022.05.030}, pmid = {35926310}, issn = {1095-8673}, mesh = {Animals ; Humans ; Infant, Newborn ; Mice ; Animals, Newborn ; Antioxidants ; Cytokines ; Disease Models, Animal ; *Enterocolitis, Necrotizing/therapy ; *Infant, Newborn, Diseases ; Intestinal Mucosa ; Mice, Inbred C57BL ; *Probiotics/pharmacology/therapeutic use ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is a promising therapy, but it has not been used to treat neonatal necrotizing enterocolitis (NEC) due to reports of adverse side effects. Probiotics are considered relatively safe with practicable administrative procedures; however, no systematic research has compared the results of FMT and probiotic consortium transplantation (PCT) on oxidative stress in the intestines of patients with NEC. We conducted this study to provide a basis for optimizing NEC therapy.<br><br>METHODS: Eight-day-old newborn C57BL/6 mice were randomly divided into the following four groups: the dam-fed group (control group); the NEC induction group (NEC group); the NEC induction and transplantation of Lactobacillus reuteri and Bifidobacterium infantis consortium group (NEC&#xa0;+&#xa0;PCT group); and the NEC induction and the FMT group (NEC&#xa0;+&#xa0;FMT). Intestinal injury, oxidative stress indexes, intestinal barrier function, and inflammatory cytokines were assessed in the terminal ileum.<br><br>RESULTS: FMT more effectively modulates oxidative stress in the intestine than does PCT; however, the difference between the effects of PCT and FMT was not significant. The protective effect was associated with enhanced antioxidant capacity, regulation of the main components of the mucus layer, reduced inflammatory reactions, and improved intestinal integrity.<br><br>CONCLUSIONS: Intestinal dysbiosis affects oxidative stress, inflammatory response, and mucosal integrity. Although FMT is more effective than PCT in regulating oxidative stress, PCT may be preferred in pediatrics because the proportion and dose of transplanted bacteria can be standardized and individualized according to individual conditions.}, }
@article {pmid35924173, year = {2022}, author = {Qin, H and Yuan, B and Huang, W and Wang, Y}, title = {Utilizing Gut Microbiota to Improve Hepatobiliary Tumor Treatments: Recent Advances.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {924696}, pmid = {35924173}, issn = {2234-943X}, abstract = {Hepatobiliary tumors, which include cholangiocarcinoma, hepatocellular carcinoma (HCC), and gallbladder cancer, are common cancers that have high morbidity and mortality rates and poor survival outcomes. In humans, the microbiota is comprised of symbiotic microbial cells (10-100 trillion) that belong to the bacterial ecosystem mainly residing in the gut. The gut microbiota is a complicated group that can largely be found in the intestine and has a dual role in cancer occurrence and progression. Previous research has focused on the crucial functions of the intestinal microflora as the main pathophysiological mechanism in HCC development. Intestinal bacteria produce a broad range of metabolites that exhibit a variety of pro- and anticarcinogenic effects on HCC. Therefore, probiotic alteration of the gut microflora could promote gut flora balance and help prevent the occurrence of HCC. Recent evidence from clinical and translational studies suggests that fecal microbiota transplant is one of the most successful therapies to correct intestinal bacterial imbalance. We review the literature describing the effects and mechanisms of the microbiome in the gut in the context of HCC, including gut bacterial metabolites, probiotics, antibiotics, and the transplantation of fecal microbiota, and discuss the potential influence of the microbiome environment on cholangiocarcinoma and gallbladder cancer. Our findings are expected to reveal therapeutic targets for the prevention of hepatobiliary tumors, and the development of clinical treatment strategies, by emphasizing the function of the gut microbiota.}, }
@article {pmid35923396, year = {2022}, author = {Huang, S and Zheng, G and Men, H and Wang, W and Li, S}, title = {The Response of Fecal Microbiota and Host Metabolome in Dairy Cows Following Rumen Fluid Transplantation.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {940158}, pmid = {35923396}, issn = {1664-302X}, abstract = {Rumen fluid transplantation (RFT) has been used to rebuild rumen bacterial homeostasis, reshape rumen function, and restore rumen fermentation, whereas the effect of RFT on fecal microbiota and host metabolism in cows remains poorly understood. In our study, a combination of 16S rRNA sequencing and serum non-targeted metabolomics was performed to investigate the response of fecal microbiota and serum metabolome in dairy cows following RFT. Twenty-four prepartum dairy cows were randomly assigned to 3 groups (n = 8) for infusion of either saline (Con), fresh rumen fluid (FR), or sterilized rumen fluid (SR) after calving. Fourteen days after calving, fecal microbiota and serum metabolome were analyzed. The sequencing data of fecal samples revealed no changes in alpha diversity and relative abundance of dominant genera such as Ruminococcaceae UCG-005, Rikenellaceae RC9 gut and Eubacterium coprostanoligenes. However, the other genus level taxa, such as Eubacterium oxidoreducens, Anaerorhabdus furcosa, Bacillus and Selenomonas, showed distinct changes following RFT. Serum metabolome analysis showed that FR or SR infusion affected amino acids metabolism, bile acids metabolism and fatty acids metabolism (including linoleic acid, oleic acid and palmitic acid). Furthermore, correlation analysis showed that taxa from genera Clostridiales were positively correlated with metabolites involved in tryptophan and bile acid metabolisms, such as OTU1039 from genera unclassified o_Clostridiales was positively correlated to indoleacetic acid and taurolithocholic acid. These results suggest that RFT altered the composition of the fecal microbiota and modulated microbial metabolic pathways, which is vital for the development and safety assessment of rumen microbial intervention strategies.}, }
@article {pmid35921529, year = {2022}, author = {Khan, MH and Onyeaghala, GC and Rashidi, A and Holtan, SG and Khoruts, A and Israni, A and Jacobson, PA and Staley, C}, title = {Fecal β-glucuronidase activity differs between hematopoietic cell and kidney transplantation and a possible mechanism for disparate dose requirements.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2108279}, pmid = {35921529}, issn = {1949-0984}, support = {R01 AI140303/AI/NIAID NIH HHS/United States ; P30 CA077598/CA/NCI NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome ; Glucuronidase ; *Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents ; *Kidney Transplantation ; Mycophenolic Acid ; }, abstract = {The intestinal microbiota produces β-glucuronidase that plays an essential role in the metabolism of the immunosuppressant mycophenolate mofetil (MMF). This drug is commonly used in organ and hematopoietic cell transplantation (HCT), with variations in dosing across transplant types. We hypothesized that β-glucuronidase activity differs between transplant types, which may account for differences in dosing requirements. We evaluated fecal β-glucuronidase activity in patients receiving MMF post-allogeneic HCT and post-kidney transplant. Kidney transplant patients had significantly greater β-glucuronidase activity (8.48 ± 6.21 nmol/hr/g) than HCT patients (3.50 ± 3.29 nmol/hr/g; P = .001). Microbially mediated β-glucuronidase activity may be a critical determinant in the amount of mycophenolate entering the systemic circulation and an important factor to consider for precision dosing of MMF.}, }
@article {pmid35921199, year = {2023}, author = {Juárez-Fernández, M and Goikoetxea-Usandizaga, N and Porras, D and García-Mediavilla, MV and Bravo, M and Serrano-Maciá, M and Simón, J and Delgado, TC and Lachiondo-Ortega, S and Martínez-Flórez, S and Lorenzo, &#xd3; and Rincón, M and Varela-Rey, M and Abecia, L and Rodríguez, H and Anguita, J and Nistal, E and Martínez-Chantar, ML and Sánchez-Campos, S}, title = {Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression.}, journal = {Hepatology (Baltimore, Md.)}, volume = {77}, number = {5}, pages = {1654-1669}, pmid = {35921199}, issn = {1527-3350}, mesh = {Mice ; Animals ; *Non-alcoholic Fatty Liver Disease/metabolism ; *Gastrointestinal Microbiome/genetics ; Mice, Inbred C57BL ; Liver/metabolism ; Diet, High-Fat/adverse effects ; Molecular Chaperones/metabolism ; Mitochondrial Proteins/metabolism ; }, abstract = {BACKGROUND AND AIMS: Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut-liver status. However, the underlying mechanism remains unclear. Herein, we hypothesized that enhanced mitochondrial activity might reshape a specific microbiota signature that, when transferred to germ-free (GF) mice, could delay NASH progression.<br><br>APPROACH AND RESULTS: Wild-type and methylation-controlled J protein knockout (MCJ-KO) mice were fed for 6&#x2009;weeks with either control or a choline-deficient, L-amino acid-defined, high-fat diet (CDA-HFD). One mouse of each group acted as a donor of cecal microbiota to GF mice, who also underwent the CDA-HFD model for 3&#x2009;weeks. Hepatic injury, intestinal barrier, gut microbiome, and the associated fecal metabolome were then studied. Following 6&#x2009;weeks of CDA-HFD, the absence of methylation-controlled J protein, an inhibitor of mitochondrial complex I activity, reduced hepatic injury and improved gut-liver axis in an aggressive NASH dietary model. This effect was transferred to GF mice through cecal microbiota transplantation. We suggest that the specific microbiota profile of MCJ-KO, characterized by an increase in the fecal relative abundance of Dorea and Oscillospira genera and a reduction in AF12 , Allboaculum , and [ Ruminococcus ], exerted protective actions through enhancing short-chain fatty acids, nicotinamide adenine dinucleotide (NAD +) metabolism, and sirtuin activity, subsequently increasing fatty acid oxidation in GF mice. Importantly, we identified Dorea genus as one of the main modulators of this microbiota-dependent protective phenotype.<br><br>CONCLUSIONS: Overall, we provide evidence for the relevance of mitochondria-microbiota interplay during NASH and that targeting it could be a valuable therapeutic approach.}, }
@article {pmid35919409, year = {2022}, author = {Philip, S and Tageldin, O and Mansoor, MS and Richter, S}, title = {Successful Fecal Microbiota Transplant Delivered by Foley Catheter Through a Loop Ileostomy in a Patient With Severe Complicated Clostridioides difficile Infection.}, journal = {ACG case reports journal}, volume = {9}, number = {7}, pages = {e00801}, pmid = {35919409}, issn = {2326-3253}, abstract = {Clostridioides difficile infection (CDI) is a potentially life-threatening cause of diarrhea that can result in multiple complications. Fulminant CDI that is nonresponsive to antibiotics may require surgical ileostomy or fecal microbiota transplant (FMT). We present a case of a patient with fulminant CDI requiring surgical loop ileostomy who underwent a successful FMT delivered by Foley catheter through the ileostomy with symptom resolution. Delivery of FMT using a foley catheter in a patient with an ileostomy may be safe and effective for patients who are at a higher risk of complications associated with the instillation of FMT through colonoscopy with anesthesia.}, }
@article {pmid35918343, year = {2022}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Halaweish, H and Kaiser, T and Holtan, SG and Khoruts, A and Weisdorf, DJ and Staley, C}, title = {Compilation of longitudinal gut microbiome, serum metabolome, and clinical data in acute myeloid leukemia.}, journal = {Scientific data}, volume = {9}, number = {1}, pages = {468}, pmid = {35918343}, issn = {2052-4463}, support = {KL2 TR002492/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1TR002494//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; KL2TR002492//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; }, mesh = {Feces ; *Gastrointestinal Microbiome ; Humans ; *Leukemia, Myeloid, Acute/metabolism/microbiology ; *Metabolome ; Metabolomics/methods ; }, abstract = {Induction chemotherapy for patients with acute myeloid leukemia (AML) is a unique clinical scenario. These patients spend several weeks in the hospital, receiving multiple antibiotics, experiencing gastrointestinal mucosal damage, and suffering severe impairments in their immune system and nutrition. These factors cause major disruptions to the gut microbiota to a level rarely seen in other clinical conditions. Thus, the study of the gut microbiota in these patients can reveal novel aspects of microbiota-host relationships. When combined with the circulating metabolome, such studies could shed light on gut microbiota contribution to circulating metabolites. Collectively, gut microbiota and circulating metabolome are known to regulate host physiology. We have previously deposited amplicon sequences from 566 fecal samples from 68 AML patients. Here, we provide sample-level details and a link, using de-identified patient IDs, to additional data including serum metabolomics (260 samples from 36 patients) and clinical metadata. The detailed information provided enables comprehensive multi-omics analysis. We validate the technical quality of these data through 3 examples and demonstrate a method for integrated analysis.}, }
@article {pmid35917710, year = {2022}, author = {Liu, J and Zhang, X and Ta, X and Luo, M and Chang, X and Wang, H}, title = {Fecal microbiome transplantation attenuates manganese-induced neurotoxicity through regulation of the apelin signaling pathway by inhibition of autophagy in mouse brain.}, journal = {Ecotoxicology and environmental safety}, volume = {242}, number = {}, pages = {113925}, doi = {10.1016/j.ecoenv.2022.113925}, pmid = {35917710}, issn = {1090-2414}, mesh = {Animals ; Apelin ; Autophagy ; Brain ; *Fecal Microbiota Transplantation ; Manganese/toxicity ; Mice ; *Neurotoxicity Syndromes ; Signal Transduction ; }, abstract = {Manganese (Mn) is a common environmental pollutant. Mn exposure can lead to neurodegenerative diseases resembling Parkinson's disease, and has become a major public health concern. However, the mechanism of Mn-induced neurotoxicity in the brain is not clear. Fecal microbiome transplantation (FMT) may alleviate the neurotoxicity of Mn exposure by remodeling the gut microbiota. In this study, MnCl2 (manganese chloride) was administered to mice as in drinking water (Mn: 200 mg/L), and fecal matter from donor mice was administered by oral gavage every other day to the recipient mice. The Mn exposure model (Mn group) and FMT model (Mn+FMT group) were established and analyzed 5 weeks post-exposure. The Wipi1 gene exhibited the most significant increase associated with Mn exposure and Mn+FMT treatment groups based on transcriptome analysis. Combined analysis of transcriptomics and proteomics demonstrated that the apelin signaling pathway is the main pathway affected by FMT during Mn exposure. Immunofluorescence and Western blot showed that the expression of key proteins (Beclin-1, LC-3B, and PINK1) associated with autophagy in the hippocampus was robustly activated in the Mn exposure group, but attenuation was observed in Mn+FMT mice, suggesting a critical role of autophagy in neurotoxicity induced by Mn exposure. Our research provides evidence for the neurotoxic effects of Mn exposure through autophagy activation and provides an underlying mechanism of FMT protection against Mn-induced neurotoxicity through regulation of the apelin signaling pathway.}, }
@article {pmid35917175, year = {2022}, author = {Tchitchek, N and Nguekap Tchoumba, O and Pires, G and Dandou, S and Campagne, J and Churlaud, G and Fourcade, G and Hoffmann, TW and Strozzi, F and Gaal, C and Bonny, C and Le Chatelier, E and Erlich, SD and Sokol, H and Klatzmann, D}, title = {Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation.}, journal = {JCI insight}, volume = {7}, number = {17}, pages = {}, pmid = {35917175}, issn = {2379-3708}, mesh = {Animals ; *Autoimmune Diseases ; Autoimmunity ; Dextran Sulfate/toxicity ; *Gastrointestinal Microbiome ; Humans ; Inflammation/therapy ; Interleukin-2/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; }, abstract = {Gut microbiota dysbiosis is associated with inflammatory bowel diseases and with cardiometabolic, neurological, and autoimmune diseases. Gut microbiota composition has a direct effect on the immune system, and vice versa, and it has a particular effect on Treg homeostasis. Low-dose IL-2 (IL-2LD) stimulates Tregs and is a promising treatment for autoimmune and inflammatory diseases. We aimed to evaluate the impact of IL-2LD on gut microbiota and correlatively on the immune system. We used 16S ribosomal RNA profiling and metagenomics to characterize gut microbiota of mice and humans treated or not with IL-2LD. We performed fecal microbiota transplantation (FMT) from IL-2LD-treated to naive recipient mice and evaluated its effects in models of gut inflammation and diabetes. IL-2LD markedly affected gut microbiota composition in mice and humans. Transfer of an IL-2-tuned microbiota by FMT protected C57BL/6J mice from dextran sulfate sodium-induced colitis and prevented diabetes in NOD mice. Metagenomic analyses highlighted a role for several species affected by IL-2LD and for microbial pathways involved in the biosynthesis of amino acids, short-chain fatty acids, and L-arginine. Our results demonstrate that IL-2LD induced changes in gut microbiota that are involved in the immunoregulatory effects of IL-2LD and suggest a crosstalk between Tregs and gut microbiota. These results provide potentially novel insight for understanding the mode of action of Treg-directed therapies.}, }
@article {pmid35914739, year = {2023}, author = {Geng, J and Liu, C and Xu, J and Wang, X and Li, X}, title = {Potential relationship between Tourette syndrome and gut microbiome.}, journal = {Jornal de pediatria}, volume = {99}, number = {1}, pages = {11-16}, pmid = {35914739}, issn = {1678-4782}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Quality of Life ; *Tourette Syndrome ; Brain ; *Probiotics/therapeutic use ; }, abstract = {OBJECTIVE: In this article, the author aims to discuss and review the relationship between gut microbiota and Tourette syndrome, and whether the change in gut microbiota can affect the severity of Tourette syndrome.<br><br>SOURCES: Literature from PubMed, Google Scholar, and China National Knowledge Infrastructure was mainly reviewed. Both original studies and review articles were discussed. The articles were required to be published as of May 2022.<br><br>SUMMARY OF THE FINDINGS: Current studies on the gut microbiome have found that the gut microbiome and brain seem to interact. It is named the brain-gut-axis. The relationship between the brain-gut axis and neurological and psychiatric disorders has been a topic of intense interest. Tourette syndrome is a chronic neurological disease that seriously affects the quality of life of children, and there appears to be an increase in Ruminococcaceae and Bacteroides in the gut of patients with Tourette syndrome. After clinical observation and animal experiments, there appear to be particular gut microbiota changes in Tourette syndrome. It provides a new possible idea for the treatment of Tourette syndrome. Probiotics and fecal microbial transplantation have been tried to treat Tourette syndrome, especially Tourette syndrome which is not sensitive to drugs, and some results have been achieved.<br><br>CONCLUSIONS: The relationship between gut microbiota and Tourette syndrome and how to alleviate Tourette syndrome by improving gut microbiota are new topics, more in-depth and larger sample size research is still needed.}, }
@article {pmid35914438, year = {2022}, author = {Medel-Matus, JS and Simpson, CA and Ahdoot, AI and Shin, D and Sankar, R and Jacobs, JP and Mazarati, AM}, title = {Modification of post-traumatic epilepsy by fecal microbiota transfer.}, journal = {Epilepsy &amp; behavior : E&amp;B}, volume = {134}, number = {}, pages = {108860}, doi = {10.1016/j.yebeh.2022.108860}, pmid = {35914438}, issn = {1525-5069}, support = {IK2 CX001717/CX/CSRD VA/United States ; }, mesh = {Animals ; *Brain Injuries, Traumatic ; *Epilepsy ; *Epilepsy, Post-Traumatic ; Fecal Microbiota Transplantation ; Humans ; Male ; Prospective Studies ; Rats ; Rats, Sprague-Dawley ; Seizures ; }, abstract = {It has been well established that traumatic brain injury (TBI) modifies the composition of gut microbiome. Epilepsy, which represents one of the common sequelae of TBI, has been associated with dysbiosis. Earlier study showed that the risk of post-traumatic epilepsy (PTE) after lateral fluid percussion injury (LFPI) in rats can be stratified based on pre-existing (i.e., pre-TBI) gut microbiome profile. In the present study, we examined whether fecal microbiota transfer (FMT) from naïve rats with different prospective histories of PTE would affect the trajectory of PTE in recipients. Fecal samples were collected from naïve adult male Sprague-Dawley rats, followed by LFPI. Seven months later, upon four weeks of vide-EEG monitoring (vEEG), the rats were categorized as those with and without PTE. Recipients were subjected to LFPI, followed by FMT from donors with and without impending PTE. Control groups included auto-FMT and no-FMT subjects. Seven month after LFPI, recipients underwent four-week vEEG to detect spontaneous seizures. After completing vEEG, rats of all groups underwent kindling of basolateral amygdala. Fecal microbiota transfer from donors with impending PTE exerted mild-to-moderate pro-epileptic effects in recipients, evident as marginal increase in multiple spontaneous seizure incidence, and facilitation of kindling. Analysis of fecal samples in selected recipients and their respective donors confirmed that FMT modified microbiota in recipients along the donors' lines, albeit without full microbiome conversion. The findings provide further evidence that gut microbiome may actively modulate the susceptibility to epilepsy.}, }
@article {pmid35913161, year = {2022}, author = {Lesniak, NA and Tomkovich, S and Henry, A and Taylor, A and Colovas, J and Bishop, L and McBride, K and Schloss, PD}, title = {Diluted Fecal Community Transplant Restores Clostridioides difficile Colonization Resistance to Antibiotic-Perturbed Murine Communities.}, journal = {mBio}, volume = {13}, number = {4}, pages = {e0136422}, pmid = {35913161}, issn = {2150-7511}, support = {U19 AI090871/AI/NIAID NIH HHS/United States ; R01 GM099514/GM/NIGMS NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacteria/genetics ; Cefoperazone/pharmacology ; Clindamycin/pharmacology/therapeutic use ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/microbiology/prevention &amp; control ; Disease Susceptibility ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Streptomycin/pharmacology/therapeutic use ; }, abstract = {Fecal communities transplanted into individuals can eliminate recurrent Clostridioides difficile infection (CDI) with high efficacy. However, this treatment is only used once CDI becomes resistant to antibiotics or has recurred multiple times. We sought to investigate whether a fecal community transplant (FCT) pretreatment could be used to prevent CDI altogether. We treated male C57BL/6 mice with either clindamycin, cefoperazone, or streptomycin and then inoculated them with the microbial community from untreated mice before challenge with C. difficile. We measured colonization and sequenced the V4 region of the 16S rRNA gene to understand the dynamics of the murine fecal community in response to the FCT and C. difficile challenge. Clindamycin-treated mice became colonized with C. difficile but cleared it naturally and did not benefit from the FCT. Cefoperazone-treated mice became colonized by C. difficile, but the FCT enabled clearance of C. difficile. In streptomycin-treated mice, the FCT was able to prevent C. difficile from colonizing. We then diluted the FCT and repeated the experiments. Cefoperazone-treated mice no longer cleared C. difficile. However, streptomycin-treated mice colonized with 1:10[2] dilutions resisted C. difficile colonization. Streptomycin-treated mice that received an FCT diluted 1:10[3] became colonized with C. difficile but later cleared the infection. In streptomycin-treated mice, inhibition of C. difficile was associated with increased relative abundance of a group of bacteria related to Porphyromonadaceae and Lachnospiraceae. These data demonstrate that C. difficile colonization resistance can be restored to a susceptible community with an FCT as long as it complements the missing populations. IMPORTANCE Antibiotic use, ubiquitous with the health care environment, is a major risk factor for Clostridioides difficile infection (CDI), the most common nosocomial infection. When C. difficile becomes resistant to antibiotics, a fecal microbiota transplant from a healthy individual can effectively restore the gut bacterial community and eliminate the infection. While this relationship between the gut bacteria and CDI is well established, there are no therapies to treat a perturbed gut community to prevent CDI. This study explored the potential of restoring colonization resistance to antibiotic-induced susceptible gut communities. We described the effect that gut bacterial community variation has on the effectiveness of a fecal community transplant for inhibiting CDI. These data demonstrated that communities susceptible to CDI can be supplemented with fecal communities but that the effectiveness depended on the structure of the community following the perturbation. Thus, a reduced bacterial community may be able to recover colonization resistance in patients treated with antibiotics.}, }
@article {pmid35911731, year = {2022}, author = {Huang, J and Zheng, X and Kang, W and Hao, H and Mao, Y and Zhang, H and Chen, Y and Tan, Y and He, Y and Zhao, W and Yin, Y}, title = {Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {874922}, pmid = {35911731}, issn = {1664-3224}, mesh = {Animals ; Bacteroides ; *Colorectal Neoplasms/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Metagenome ; Mice ; }, abstract = {Anti-PD-1 immunotherapy has saved numerous lives of cancer patients; however, it only exerts efficacy in 10-15% of patients with colorectal cancer. Fecal microbiota transplantation (FMT) is a potential approach to improving the efficacy of anti-PD-1 therapy, whereas the detailed mechanisms and the applicability of this combination therapy remain unclear. In this study, we evaluated the synergistic effect of FMT with anti-PD-1 in curing colorectal tumor-bearing mice using a multi-omics approach. Mice treated with the combination therapy showed superior survival rate and tumor control, compared to the mice received anti-PD-1 therapy or FMT alone. Metagenomic analysis showed that composition of gut microbiota in tumor-bearing mice treated with anti-PD-1 therapy was remarkably altered through receiving FMT. Particularly, Bacteroides genus, including FMT-increased B. thetaiotaomicron, B. fragilis, and FMT-decreased B. ovatus might contribute to the enhanced efficacy of anti-PD-1 therapy. Furthermore, metabolomic analysis upon mouse plasma revealed several potential metabolites that upregulated after FMT, including punicic acid and aspirin, might promote the response to anti-PD-1 therapy via their immunomodulatory functions. This work broadens our understanding of the mechanism by which FMT improves the efficacy of anti-PD-1 therapy, which may contribute to the development of novel microbiota-based anti-cancer therapies.}, }
@article {pmid35911670, year = {2022}, author = {Wang, J and Jia, R and Celi, P and Zhuo, Y and Ding, X and Zeng, Q and Bai, S and Xu, S and Yin, H and Lv, L and Zhang, K}, title = {Resveratrol Alleviating the Ovarian Function Under Oxidative Stress by Alternating Microbiota Related Tryptophan-Kynurenine Pathway.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {911381}, pmid = {35911670}, issn = {1664-3224}, mesh = {Animals ; Female ; Kynurenine/metabolism ; *Microbiota ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress ; Resveratrol/pharmacology ; *Sirtuin 1/metabolism ; Tryptophan/metabolism/pharmacology ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Oxidative stress (OS) is a key factor regulating the systemic pathophysiological effects and one of the fundamental mechanisms associated with aging and fertility deterioration. Previous studies revealed that resveratrol (RV) exhibits a preventive effect against oxidative stress in the ovary. However, it remains unknown whether gut microbiota respond to resveratrol during an OS challenge. In Exp. 1, layers received intraperitoneal injection of tert-butyl hydroperoxide (tBHP) (0 or 800 μmol/kg BW) or received resveratrol diets (0 or 600 mg/kg) for 28 days. In Exp. 2, the role of intestinal microbiota on the effects of resveratrol on tBHP-induced oxidative stress was assessed through fecal microbiota transplantation (FMT). The OS challenge reduced the egg-laying rate and exhibited lower pre-hierarchical follicles and higher atretic follicles. Oral RV supplementation ameliorated the egg-laying rate reduction and gut microbiota dysbiosis. RV also reversed the tryptphan-kynurenine pathway, upregulated nuclear factor E2-related factor 2 (Nrf2) and silent information regulator 1(SIRT1) levels, and decreased the expression of forkhead box O1 (FoxO1) and P53. These findings indicated that the intestinal microbiota-related tryptophan-kynurenine pathway is involved in the resveratrol-induced amelioration of ovary oxidative stress induced by tBHP in the layer model, while SIRT1-P53/FoxO1 and Nrf2-ARE signaling pathway were involved in this process.}, }
@article {pmid35910597, year = {2022}, author = {Bo, T and Liu, M and Tang, L and Lv, J and Wen, J and Wang, D}, title = {Effects of High-Fat Diet During Childhood on Precocious Puberty and Gut Microbiota in Mice.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {930747}, pmid = {35910597}, issn = {1664-302X}, abstract = {Precocious puberty mostly stems from endocrine disorders. However, more and more studies show that a high-fat diet (HFD) is closely related to precocious puberty, but its mechanism is unknown. Since gut microbiota is associated with hormone secretion and obesity, it inspires us to detect the mechanism of gut microbiota in triggering precocious puberty. The model of precocious puberty was established by feeding female mice with an HFD from 21 days old. After puberty, the serum hormone levels, gut microbiome sequencing, and metabolomics were collected. DNA was extracted from feces, and the V3-V4 region of the bacterial 16S rRNA gene was amplified, followed by microbial composition analysis. Subsequently, associations between precocious puberty and the microbiota were determined. We found that (1) HFD after weaning caused precocious puberty, increased serum estradiol, leptin, deoxycholic acid (DCA), and gonadotropin-releasing hormone (GnRH) in the hypothalamus; (2) Through correlation analysis, we found that GnRH was positively correlated with Desulfovibrio, Lachnoclostridium, GCA-900066575, Streptococcus, Anaerotruncus, and Bifidobacterium, suggesting that these bacteria may have a role in promoting sexual development. (3) "HFD-microbiota" transplantation promoted the precocious puberty of mice. (4) Estrogen changes the composition and proportion of gut microbiota and promotes precocious puberty. Therefore, the effect of HFD on precocious puberty is regulated by the interaction of gut microbiota and hormones.}, }
@article {pmid35905229, year = {2022}, author = {Huang, T and Xu, J and Wang, M and Pu, K and Li, L and Zhang, H and Liang, Y and Sun, W and Wang, Y}, title = {An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis.}, journal = {Medicine}, volume = {101}, number = {30}, pages = {e29790}, pmid = {35905229}, issn = {1536-5964}, mesh = {*Colitis, Ulcerative/drug therapy ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Remission Induction ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) as a promising therapy for ulcerative colitis (UC) remains controversial. We conducted a systematic review and meta-analysis to assess the efficiency and safety of FMT as a treatment for UC.<br><br>METHODS: The target studies were identified by searching PubMed, EMBASE, the Cochrane Library, Web of Science, and ClinicalTrials and by manual supplementary retrieval. We conducted a general review and quantitative synthesis of included studies. We used the RevMan and Stata programs in the meta-analysis. The outcomes were total remission, clinical remission, steroid-free remission, and serious adverse events. We also performed subgroup analyses based on different populations.<br><br>RESULTS: A total of 34 articles were included in the general review. Only 16 articles, including 4 randomized controlled trials, 2 controlled clinical trials, and 10 cohort studies, were selected for the meta-analysis. We found that donor FMT might be more effective than placebo for attaining total remission (risk ratio [RR]: 2.77, 95% confidence interval [CI]: 1.54-4.98; P = .0007), clinical remission (RR: 0.33, 95% CI: 0.24-0.41; P < .05), and steroid-free remission (RR: 3.63, 95% CI: 1.57-8.42; P = .003), but found no statistically significant difference in the incidence of serious adverse events (RR: 0.88, 95% CI: 0.34-2.31, P = .8). The subgroup analyses revealed significant differences between the pooled clinical remission rates for different regions, degrees of severity of the disease, and patients with steroid- or nonsteroid-dependent UC.<br><br>CONCLUSIONS: FMT can achieve clinical remission and clinical response in patients with UC.}, }
@article {pmid35902778, year = {2022}, author = {Chen, YM and Sadiq, S and Tian, JH and Chen, X and Lin, XD and Shen, JJ and Chen, H and Hao, ZY and Wille, M and Zhou, ZC and Wu, J and Li, F and Wang, HW and Yang, WD and Xu, QY and Wang, W and Gao, WH and Holmes, EC and Zhang, YZ}, title = {RNA viromes from terrestrial sites across China expand environmental viral diversity.}, journal = {Nature microbiology}, volume = {7}, number = {8}, pages = {1312-1323}, pmid = {35902778}, issn = {2058-5276}, mesh = {Animals ; China ; Ecosystem ; Genome, Viral ; Humans ; Phylogeny ; Plants ; RNA ; *RNA Viruses/genetics ; Virome ; *Viruses/genetics ; }, abstract = {Environmental RNA viruses are ubiquitous and diverse, and probably have important ecological and biogeochemical impacts. Understanding the global diversity of RNA viruses is limited by sampling biases, dependence on cell culture and PCR for virus discovery, and a focus on viruses pathogenic to humans or economically important animals and plants. To address this knowledge gap, we generated metatranscriptomic sequence data from 32 diverse environments in 16 provinces and regions of China. We identified 6,624 putatively novel virus operational taxonomic units from soil, sediment and faecal samples, greatly expanding known diversity of the RNA virosphere. These newly identified viruses included positive-sense, negative-sense and double-strand RNA viruses from at least 62 families. Sediments and animal faeces were rich sources of viruses. Virome compositions were affected by local environmental factors, including organic content and eukaryote species abundance. Notably, environmental factors had a greater impact on the abundance and diversity of plant, fungal and bacterial viruses than of animal viromes. Our data confirm that RNA viruses are an integral part of both terrestrial and aquatic ecosystems.}, }
@article {pmid35902549, year = {2022}, author = {Li, Z and Sun, T and He, Z and Li, Z and Zhang, W and Wang, J and Xiang, H}, title = {SCFAs Ameliorate Chronic Postsurgical Pain-Related Cognition Dysfunction via the ACSS2-HDAC2 Axis in Rats.}, journal = {Molecular neurobiology}, volume = {59}, number = {10}, pages = {6211-6227}, pmid = {35902549}, issn = {1559-1182}, support = {81873467//National Natural Science Foundation of China/ ; 81670240//National Natural Science Foundation of China/ ; }, mesh = {*Acetate-CoA Ligase/metabolism ; Animals ; Cognition ; *Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome/physiology ; *Histone Deacetylase 2/metabolism ; Pain, Postoperative ; RNA, Ribosomal, 16S ; Rats ; }, abstract = {Patients with chronic postsurgical pain (CPSP) frequently exhibit comorbid cognitive deficits. Recent observations have emphasized the critical effects of gut microbial metabolites, like short-chain fatty acids (SCFAs), in regulating cognitive function. However, the underlying mechanisms and effective interventions remain unclear. According to hierarchical clustering and 16S rRNA analysis, over two-thirds of the CPSP rats had cognitive impairment, and the CPSP rats with cognitive impairment had an aberrant composition of gut SCFA-producing bacteria. Then, using feces microbiota transplantation, researchers identified a causal relationship between cognitive-behavioral and microbic changes. Similarly, the number of genera that generated SCFAs was decreased in the feces from recipients of cognitive impairment microbiota. Moreover, treatment with the SCFAs alleviated the cognitive-behavioral deficits in the cognitively compromised pain rats. Finally, we observed that SCFA supplementation improved histone acetylation and abnormal synaptic transmission in the medial prefrontal cortex (mPFC), hippocampal CA1, and central amygdala (CeA) area via the ACSS2 (acetyl-CoA synthetase2)-HDAC2 (histone deacetylase 2) axis. These findings link pain-related cognition dysfunction, gut microbiota, and short-chain fatty acids, shedding fresh insight into the pathogenesis and therapy of pain-associated cognition dysfunction.}, }
@article {pmid35899275, year = {2022}, author = {Vendrik, KEW and de Meij, TGJ and Bökenkamp, A and Ooijevaar, RE and Groenewegen, B and Hendrickx, APA and Terveer, EM and Kuijper, EJ and van Prehn, J}, title = {Transmission of Antibiotic-Susceptible Escherichia coli Causing Urinary Tract Infections in a Fecal Microbiota Transplantation Recipient: Consequences for Donor Screening?.}, journal = {Open forum infectious diseases}, volume = {9}, number = {7}, pages = {ofac324}, pmid = {35899275}, issn = {2328-8957}, abstract = {Fecal microbiota transplantation (FMT) has been reported to decrease the incidence of recurrent urinary tract infections (UTIs), presumably by restoring microbiome diversity and/or uropathogen competition. We report a 16-year-old female with recurrent UTIs caused by multidrug-resistant Klebsiella pneumoniae, for which frequent intravenous broad-spectrum antibiotic treatment was necessary. The patient was treated with FMT from a well-screened healthy donor without multidrug-resistant bacteria in the feces. After FMT, she developed several UTIs with an antibiotic-susceptible Escherichia coli that could be treated orally. The uropathogenic E. coli could be cultured from donor feces, and whole genome sequencing confirmed donor-to-recipient transmission. Our observation should stimulate discussion on long-term follow-up of all infections after FMT and donor fecal screening for antibiotic-susceptible Enterobacterales.}, }
@article {pmid35899041, year = {2022}, author = {Cheng, Z and Yang, L and Chu, H}, title = {The Gut Microbiota: A Novel Player in Autoimmune Hepatitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {947382}, pmid = {35899041}, issn = {2235-2988}, mesh = {Animals ; Ecosystem ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Hepatitis, Autoimmune/pathology ; Humans ; Mice ; *Probiotics/therapeutic use ; }, abstract = {Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease distributed globally in all ethnicities with increasing prevalence. If left untreated, the disease will lead to cirrhosis, liver failure, or death. The intestinal microbiota is a complex ecosystem located in the human intestine, which extensively affects the human physiological and pathological processes. With more and more in-depth understandings of intestinal microbiota, a substantial body of studies have verified that the intestinal microbiota plays a crucial role in a variety of digestive system diseases, including alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). However, only a few studies have paid attention to evaluate the relationship between AIH and the intestinal microbiota. While AIH pathogenesis is not fully elucidated yet, some studies have indicated that intestinal microbiota putatively made significant contributions to the occurrence and the development of AIH by triggering several specific signaling pathways, altering the metabolism of intestinal microbiota, as well as modulating the immune response in the intestine and liver. By collecting the latest related literatures, this review summarized the increasing trend of the aerobic bacteria abundance in both AIH patients and AIH mice models. Moreover, the combination of specific bacteria species was found distinct to AIH patients, which could be a promising tool for diagnosing AIH. In addition, there were alterations of luminal metabolites and immune responses, including decreased short-chain fatty acids (SCFAs), increased pathogen associated molecular patterns (PAMPs), imbalanced regulatory T (Treg)/Th17 cells, follicular regulatory T (TFR)/follicular helper T (TFH) cells, and activated natural killer T (NKT) cells. These alterations participate in the onset and the progression of AIH via multiple mechanisms. Therefore, some therapeutic methods based on restoration of intestinal microbiota composition, including probiotics and fecal microbiota transplantation (FMT), as well as targeted intestinal microbiota-associated signaling pathways, confer novel insights into the treatment for AIH patients.}, }
@article {pmid35898713, year = {2022}, author = {Guo, L and Guan, Q and Duan, W and Ren, Y and Zhang, XJ and Xu, HY and Shi, JS and Wang, FZ and Lu, R and Zhang, HL and Xu, ZH and Li, H and Geng, Y}, title = {Dietary Goji Shapes the Gut Microbiota to Prevent the Liver Injury Induced by Acute Alcohol Intake.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {929776}, pmid = {35898713}, issn = {2296-861X}, abstract = {Diet is a major driver of the structure and function of the gut microbiota, which influences the host physiology. Alcohol abuse can induce liver disease and gut microbiota dysbiosis. Here, we aim to elucidate whether the well-known traditional health food Goji berry targets gut microbiota to prevent liver injury induced by acute alcohol intake. The results showed that Goji supplementation for 14 days alleviated acute liver injury as indicated by lowering serum aspartate aminotransferase, alanine aminotransferase, pro-inflammatory cytokines, as well as lipopolysaccharide content in the liver tissue. Goji maintained the integrity of the epithelial barrier and increased the levels of butyric acid in cecum contents. Furthermore, we established the causal relationship between gut microbiota and liver protection effects of Goji with the help of antibiotics treatment and fecal microbiota transplantation (FMT) experiments. Both Goji and FMT-Goji increased glutathione (GSH) in the liver and selectively enriched the butyric acid-producing gut bacterium Akkermansia and Ruminococcaceae by using 16S rRNA gene sequencing. Metabolomics analysis of cecum samples revealed that Goji and its trained microbiota could regulate retinoyl β-glucuronide, vanillic acid, and increase the level of glutamate and pyroglutamic acid, which are involved in GSH metabolism. Our study highlights the communication among Goji, gut microbiota, and liver homeostasis.}, }
@article {pmid35898289, year = {2022}, author = {Liu, Y and Zhang, S and Wu, X and Li, Q and Wang, Y and Huang, Y and Zhang, F and Cui, B and Lu, X}, title = {Instant messaging client gives the opportunity to recognize gut microbiota and dysbiosis-related disease: An investigation study on WeChat APP.}, journal = {Digital health}, volume = {8}, number = {}, pages = {20552076221115018}, pmid = {35898289}, issn = {2055-2076}, abstract = {OBJECTIVES: Gut microbiota and dysbiosis are closely related to the occurrence and development of various diseases. It is necessary to popularize gut microbiota-related knowledge to the public. And the instant messaging client on smartphones supplies a perfect tool to achieve this goal. Hence, we will describe the current status of gut microbiota education spread by WeChat official accounts.<br><br>METHODS: The keywords of "gut microbiota," "fecal microbiota transplantation (FMT)," and "probiotics" were searched in the articles published from January 2015 to August 2020 on the WeChat official accounts. And the data were analyzed based on the 10 common gut dysbiosis-related diseases.<br><br>RESULTS: A total of 3061 WeChat official accounts have published 11,239 articles on gut microbiota dysbiosis-related diseases, with a rising trend in the total article numbers and the total pageviews. The keywords of "gut microbiota" dominate 50.61%, and the articles on inflammatory bowel disease had the largest proportion. Additionally, articles on the keyword "gut microbiota" also included cancer and obesity, articles on the keyword "FMT" mainly consist of Clostridium difficile infection and psychological disease, and the keyword "probiotics" was mainly related to obesity and irritable bowel syndrome disease. The top three total pageviews were on inflammatory bowel disease, obesity, and cancer.<br><br>CONCLUSION: This study indicates the current research hotspots and public concerns on the gut microbiota, and WeChat as an instant messaging client plays an important role in promoting the scientific popularization of gut microbiota.}, }
@article {pmid35891335, year = {2022}, author = {Swartling, L and Sparrelid, E and Ljungman, P and Boriskina, K and Valentini, D and Svensson, L and Nordgren, J}, title = {The Importance of Secretor-Status in Norovirus Infection Following Allogeneic Hematopoietic Stem Cell Transplantation.}, journal = {Viruses}, volume = {14}, number = {7}, pages = {}, pmid = {35891335}, issn = {1999-4915}, mesh = {*Caliciviridae Infections ; Feces ; Genotype ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; *Norovirus/genetics ; Retrospective Studies ; }, abstract = {Background. Human secretor-status is a strong susceptibility factor for norovirus infection in immunocompetent people. The predominant norovirus genotype GII.4 almost exclusively infects secretors and is also associated with more severe symptoms. However, it is not known to what extent this also applies to immunocompromised individuals. Our objective was to determine the importance of secretor-status and norovirus genotype for the susceptibility and/or the clinical course of norovirus infection in allogeneic hematopoietic stem cell transplant (HCT) patients. Methods: This was a retrospective study of 89 HCT patients diagnosed with norovirus infection. Secretor-status and norovirus genotype were determined using stored extracted DNA or blood (n = 89) and fecal samples (n = 22), respectively. Results: Seven of eighty-nine (8%) of the patients were secretor-negative, a small proportion compared to the expected rate of at least 20% non-secretors in the general Swedish population. Among the genotyped samples, norovirus genotype GII.4 was predominant (n = 12) and only detected in secretor-positive individuals. Patients with norovirus GII.4 had a median symptom duration of 36 (3-681) days compared to 15 (1-94) days in patients infected with other norovirus genotypes (n = 10, p = 0.1). Conclusions: The results suggest that secretor-status affects the susceptibility to norovirus infection even when the immune system is severely compromised. The norovirus genotype may also be a risk factor for chronic norovirus symptoms in immunocompromised patients.}, }
@article {pmid35890040, year = {2022}, author = {Dinan, K and Dinan, TG}, title = {Gut Microbes and Neuropathology: Is There a Causal Nexus?.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {7}, pages = {}, pmid = {35890040}, issn = {2076-0817}, abstract = {The gut microbiota is a virtual organ which produces a myriad of molecules that the brain and other organs require. Humans and microbes are in a symbiotic relationship, we feed the microbes, and in turn, they provide us with essential molecules. Bacteroidetes and Firmicutes phyla account for around 80% of the total human gut microbiota, and approximately 1000 species of bacteria have been identified in the human gut. In adults, the main factors influencing microbiota structure are diet, exercise, stress, disease and medications. In this narrative review, we explore the involvement of the gut microbiota in Parkinson's disease, Alzheimer's disease, multiple sclerosis and autism, as these are such high-prevalence disorders. We focus on preclinical studies that increase the understanding of disease pathophysiology. We examine the potential for targeting the gut microbiota in the development of novel therapies and the limitations of the currently published clinical studies. We conclude that while the field shows enormous promise, further large-scale studies are required if a causal link between these disorders and gut microbes is to be definitively established.}, }
@article {pmid35889090, year = {2022}, author = {Gubatan, J and Boye, TL and Temby, M and Sojwal, RS and Holman, DR and Sinha, SR and Rogalla, SR and Nielsen, OH}, title = {Gut Microbiome in Inflammatory Bowel Disease: Role in Pathogenesis, Dietary Modulation, and Colitis-Associated Colon Cancer.}, journal = {Microorganisms}, volume = {10}, number = {7}, pages = {}, pmid = {35889090}, issn = {2076-2607}, support = {L30 DK126220/DK/NIDDK NIH HHS/United States ; }, abstract = {The gut microbiome has increasingly been recognized as a critical and central factor in inflammatory bowel disease (IBD). Here, we review specific microorganisms that have been suggested to play a role in the pathogenesis of IBD and the current state of fecal microbial transplants as a therapeutic strategy in IBD. We discuss specific nutritional and dietary interventions in IBD and their effects on gut microbiota composition. Finally, we examine the role and mechanisms of the gut microbiome in mediating colitis-associated colon cancer.}, }
@article {pmid35889051, year = {2022}, author = {Mazzawi, T}, title = {Gut Microbiota Manipulation in Irritable Bowel Syndrome.}, journal = {Microorganisms}, volume = {10}, number = {7}, pages = {}, pmid = {35889051}, issn = {2076-2607}, abstract = {Increased knowledge suggests that disturbed gut microbiota, termed dysbiosis, might promote the development of irritable bowel syndrome (IBS) symptoms. Accordingly, gut microbiota manipulation has evolved in the last decade as a novel treatment strategy in order to improve IBS symptoms. In using different approaches, dietary management stands first in line, including dietary fiber supplements, prebiotics, and probiotics that are shown to change the composition of gut microbiota, fecal short-chain fatty acids and enteroendocrine cells densities and improve IBS symptoms. However, the exact mixture of beneficial bacteria for each individual remains to be identified. Prescribing nonabsorbable antibiotics still needs confirmation, although using rifaximin has been approved for diarrhea-predominant IBS. Fecal microbiota transplantation (FMT) has recently gained a lot of attention, and five out of seven placebo-controlled trials investigating FMT in IBS obtain promising results regarding symptom reduction and gut microbiota manipulation. However, more data, including larger cohorts and studying long-term effects, are needed before FMT can be regarded as a treatment for IBS in clinical practice.}, }
@article {pmid35889034, year = {2022}, author = {Del Vecchio, LE and Fiorani, M and Tohumcu, E and Bibbò, S and Porcari, S and Mele, MC and Pizzoferrato, M and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {Risk Factors, Diagnosis, and Management of Clostridioides difficile Infection in Patients with Inflammatory Bowel Disease.}, journal = {Microorganisms}, volume = {10}, number = {7}, pages = {}, pmid = {35889034}, issn = {2076-2607}, abstract = {Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD) are two pathologies that share a bidirectional causal nexus, as CDI is known to have an aggravating effect on IBD and IBD is a known risk factor for CDI. The colonic involvement in IBD not only renders the host more prone to an initial CDI development but also to further recurrences. Furthermore, IBD flares, which are predominantly set off by a CDI, not only create a need for therapy escalation but also prolong hospital stay. For these reasons, adequate and comprehensive management of CDI is of paramount importance in patients with IBD. Microbiological diagnosis, correct evaluation of clinical status, and consideration of different treatment options (from antibiotics and fecal microbiota transplantation to monoclonal antibodies) carry pivotal importance. Thus, the aim of this article is to review the risk factors, diagnosis, and management of CDI in patients with IBD.}, }
@article {pmid35888994, year = {2022}, author = {Trunfio, M and Scabini, S and Rugge, W and Bonora, S and Di Perri, G and Calcagno, A}, title = {Concurrent and Subsequent Co-Infections of Clostridioides difficile Colitis in the Era of Gut Microbiota and Expanding Treatment Options.}, journal = {Microorganisms}, volume = {10}, number = {7}, pages = {}, pmid = {35888994}, issn = {2076-2607}, abstract = {We narratively reviewed the physiopathology, epidemiology, and management of co-infections in Clostridioides difficile colitis (CDI) by searching the following keywords in Embase, MedLine, and PubMed: "Clostridium/Clostridioides difficile", "co-infection", "blood-stream infection" (BSI), "fungemia", "Candida", "Cytomegalovirus", "probiotics", "microbial translocation" (MT). Bacterial BSIs (mainly by Enterobacteriaceae and Enterococcus) and fungemia (mainly by Candida albicans) may occur in up to 20% and 9% of CDI, increasing mortality and length of hospitalization. Up to 68% of the isolates are multi-drug-resistant bacteria. A pivotal role is played by gut dysbiosis, intestinal barrier leakage, and MT. Specific risk factors are represented by CDI-inducing broad-spectrum antibiotics, oral vancomycin use, and CDI severity. Probiotics administration (mainly Saccharomyces and Lactobacillus) during moderate/severe CDI may favor probiotics superinfection. Other co-infections (such as Cytomegalovirus or protozoa) can complicate limited and specific cases. There is mounting evidence that fidaxomicin, bezlotoxumab, and fecal microbiota transplantation can significantly reduce the rate of co-infections compared to historical therapies by interrupting the vicious circle between CDI, treatments, and MT. Bacterial BSIs and candidemia represent the most common co-infections in CDI. Physicians should be aware of this complication to promptly diagnose and treat it and enforce preventive strategies that include a more comprehensive consideration of newer treatment options.}, }
@article {pmid35888624, year = {2022}, author = {Qashqari, FS}, title = {Seroprevalence of Hepatitis E Virus Infection in Middle Eastern Countries: A Systematic Review and Meta-Analysis.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {7}, pages = {}, pmid = {35888624}, issn = {1648-9144}, mesh = {Female ; Hepatitis Antibodies ; *Hepatitis E/epidemiology ; *Hepatitis E virus ; Humans ; Middle East/epidemiology ; Pregnancy ; Seroepidemiologic Studies ; }, abstract = {Hepatitis E virus (HEV) is a hepatotropic virus that is a major public health concern worldwide. Autochthonous HEV is spread through oral feces in unsanitary environments, as well as vertical and, occasionally, blood transfusion. HEV is more common in developing countries, but it has recently become more widespread in developed countries as well. The Middle East (ME) has long been an endemic location for HEV infection. Therefore, the aim of this systematic review and meta-analysis was to assess the seroprevalence of anti-HEV antibodies in ME countries. The author systematically searched five databases, namely ScienceDirect, EMBASE, Scopus, PubMed, and Google Scholar, to identify English-language articles published on or before 25 April 2022. Comprehensive meta-analysis software was used for all statistical analyses (CMA, version 3, BioStat, Englewood, CO, USA). After quality control and exclusion of irrelevant studies, 80 studies were included in the qualitative synthesis and meta-analysis. A forest plot showed that the overall pooled seroprevalence of HEV infection in ME countries in the fixed-effect and random-effect models were 21.3% (95% CI: 0.209-0.216) and 11.8% (95% CI: 0.099-0.144), respectively. Furthermore, the findings showed a high level of heterogeneity (I2 = 98.733%) among the included studies. In both fixed-effect and random-effect models, the seroprevalence of HEV infection by country was high in Egypt as compared to other regions, at 35.0% (95% CI: 0.342-0.359), and 34.7% (95% CI: 0.153-0.611), respectively. The seroprevalence of HEV infection by country was high among pregnant women, at 47.9% (95% CI: 0.459-0.499) in the fixed-effect model, and in renal transplant recipients, at 30.8% (95% CI: 0.222-0.410) in the random-effect model. The seroprevalence of HEV infection varies by country and study population in the Middle East. More research is needed to determine the disease's incidence, morbidity, and mortality in the region, where it is prevalent.}, }
@article {pmid35887883, year = {2022}, author = {Biazzo, M and Deidda, G}, title = {Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases.}, journal = {Journal of clinical medicine}, volume = {11}, number = {14}, pages = {}, pmid = {35887883}, issn = {2077-0383}, abstract = {The human body is home to a variety of micro-organisms. Most of these microbial communities reside in the gut and are referred to as gut microbiota. Over the last decades, compelling evidence showed that a number of human pathologies are associated with microbiota dysbiosis, thereby suggesting that the reinstatement of physiological microflora balance and composition might ameliorate the clinical symptoms. Among possible microbiota-targeted interventions, pre/pro-biotics supplementations were shown to provide effective results, but the main limitation remains in the limited microbial species available as probiotics. Differently, fecal microbiota transplantation involves the transplantation of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition aiming to confer a health benefit. Firstly used in the 4th century in traditional Chinese medicine, nowadays, it has been exploited so far to treat recurrent Clostridioides difficile infections, but accumulating data coming from a number of clinical trials clearly indicate that fecal microbiota transplantation may also carry the therapeutic potential for a number of other conditions ranging from gastrointestinal to liver diseases, from cancer to inflammatory, infectious, autoimmune diseases and brain disorders, obesity, and metabolic syndrome. In this review, we will summarize the commonly used preparation and delivery methods, comprehensively review the evidence obtained in clinical trials in different human conditions and discuss the variability in the results and the pivotal importance of donor selection. The final aim is to stimulate discussion and open new therapeutic perspectives among experts in the use of fecal microbiota transplantation not only in Clostridioides difficile infection but as one of the first strategies to be used to ameliorate a number of human conditions.}, }
@article {pmid35887092, year = {2022}, author = {Xing, H and Zhang, Y and Krämer, M and Kissmann, AK and Amann, V and Raber, HF and Weil, T and Stieger, KR and Knippschild, U and Henkel, M and Andersson, J and Rosenau, F}, title = {A Polyclonal Aptamer Library for the Specific Binding of the Gut Bacterium Roseburia intestinalis in Mixtures with Other Gut Microbiome Bacteria and Human Stool Samples.}, journal = {International journal of molecular sciences}, volume = {23}, number = {14}, pages = {}, pmid = {35887092}, issn = {1422-0067}, support = {202108080084//China Scholarship Council/ ; 7533-10-5-186A and 7533-10-5-190//Ministerium f&#xfc;r Wissenschaft, Forschung und Kunst Baden-W&#xfc;rttemberg/ ; BiofMO_005//Baden-W&#xfc;rttemberg Stiftung/ ; MIKROBIOM: AMDA//Baden-W&#xfc;rttemberg Stiftung/ ; 686271//Horizon 2020/ ; 465229237//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Aptamers, Nucleotide/chemistry ; Bacteria/metabolism ; Clostridiales/genetics ; *Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S/genetics/metabolism ; SELEX Aptamer Technique/methods ; }, abstract = {Roseburia intestinalis has received attention as a potential probiotic bacterium. Recent studies have demonstrated that changes in its intestinal abundance can cause various diseases, such as obesity, enteritis and atherosclerosis. Probiotic administration or fecal transplantation alter the structure of the intestinal flora, offering possibilities for the prevention and treatment of these diseases. However, current monitoring methods, such as 16S rRNA sequencing, are complex and costly and require specialized personnel to perform the tests, making it difficult to continuously monitor patients during treatment. Hence, the rapid and cost-effective quantification of intestinal bacteria has become an urgent problem to be solved. Aptamers are of emerging interest because their stability, low immunogenicity and ease of modification are attractive properties for a variety of applications. We report a FluCell-SELEX polyclonal aptamer library specific for R. intestinalis isolated after seven evolution rounds, that can bind and label this organism for fluorescence microscopy and binding assays. Moreover, R. intestinalis can be distinguished from other major intestinal bacteria in complex defined mixtures and in human stool samples. We believe that this preliminary evidence opens new avenues towards aptamer-based electronic biosensors as new powerful and inexpensive diagnostic tools for the relative quantitative monitoring of R. intestinalis in gut microbiomes.}, }
@article {pmid35884791, year = {2022}, author = {Ghezzi, L and Cantoni, C and Rotondo, E and Galimberti, D}, title = {The Gut Microbiome-Brain Crosstalk in Neurodegenerative Diseases.}, journal = {Biomedicines}, volume = {10}, number = {7}, pages = {}, pmid = {35884791}, issn = {2227-9059}, abstract = {The gut-brain axis (GBA) is a complex interactive network linking the gut to the brain. It involves the bidirectional communication between the gastrointestinal and the central nervous system, mediated by endocrinological, immunological, and neural signals. Perturbations of the GBA have been reported in many neurodegenerative diseases, suggesting a possible role in disease pathogenesis, making it a potential therapeutic target. The gut microbiome is a pivotal component of the GBA, and alterations in its composition have been linked to GBA dysfunction and CNS inflammation and degeneration. The gut microbiome might influence the homeostasis of the central nervous system homeostasis through the modulation of the immune system and, more directly, the production of molecules and metabolites. Small clinical and preclinical trials, in which microbial composition was manipulated using dietary changes, fecal microbiome transplantation, and probiotic supplements, have provided promising outcomes. However, results are not always consistent, and large-scale randomized control trials are lacking. Here, we give an overview of how the gut microbiome influences the GBA and could contribute to disease pathogenesis in neurodegenerative diseases.}, }
@article {pmid35884093, year = {2022}, author = {Hong, AS and Tun, KM and Hong, JM and Batra, K and Ohning, G}, title = {Fecal Microbiota Transplantation in Decompensated Cirrhosis: A Systematic Review on Safety and Efficacy.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {7}, pages = {}, pmid = {35884093}, issn = {2079-6382}, abstract = {Background and Aims: Due to increasing knowledge of the "gut-liver axis", there has been growing interest regarding the use of fecal microbiota transplant in the management of chronic liver disease. There are limited data available and current guidelines are mostly based on expert opinions. We aim to perform the first systematic review investigating safety and efficacy of fecal microbiota transplant particularly among high-risk decompensated cirrhosis patient populations. Methods: Literature search was performed using variations of the keywords "fecal microbiota transplant" and "cirrhosis" on PubMed/Medline from inception to 3 October 2021. The resulting 116 articles were independently screened by two authors. In total, 5 qualifying studies, including 2 randomized control trials and 3 retrospective case series, were found to meet established eligibility criteria and have adequate quality of evidence to be included in this review. Results: Of the total 58 qualifying patients, there were 2 deaths post fecal microbiota transplant, 1 of which could not rule out being related (1.7%). Among the remaining 56 participants, 8 serious adverse events were reported, of which 2 could not rule out being related (3.6%). The success rate of fecal microbiota transplantation in treating recurrent Clostridioides difficile infection among patients with decompensated cirrhosis was 77.8%. The success rate when used as investigational treatment for hepatic encephalopathy was 86.7%, with multiple studies reporting clinically significant improvement in encephalopathy testing scores. Conclusions: We found a marginally higher rate of deaths and serious adverse events from fecal microbiota transplant in our patient population compared with the average immunocompetent population, where it was previously found to have 0 deaths and SAE rate of 2.83%. The efficacy when used for recurrent C.difficile infection was 77.8% and 87% in the decompensated cirrhotic and general populations, respectively. Studies on efficacy in novel treatment of hepatic encephalopathy have been promising. This study concludes that fecal microbiota transplant use in decompensated cirrhosis patients should be used with caution and preferably be limited to research purposes until better data are available.}, }
@article {pmid35882675, year = {2022}, author = {Shi, X and Ma, T and Sakandar, HA and Menghe, B and Sun, Z}, title = {Gut microbiome and aging nexus and underlying mechanism.}, journal = {Applied microbiology and biotechnology}, volume = {106}, number = {17}, pages = {5349-5358}, pmid = {35882675}, issn = {1432-0614}, support = {No.2020ZD12//Natural Science Foundation of Inner Mongolia/ ; 2021ZD0014//Agriculture Research System of China/ ; 2018YFE0123500//Key Technologies Research and Development Program/ ; }, mesh = {Aged ; Aged, 80 and over ; Aging ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Longevity ; Middle Aged ; *Probiotics ; }, abstract = {According to the United Nations population profile, the number of individuals aged 60 and over in high-income nations is expected to rise from 302 million to over 366 million between 2019 and 2030, so there is an increasing emphasis on nutrition and health in older people. Numerous studies have demonstrated the crucial role that gut microbiota plays in maintaining human health. As a model of healthy aging, centenarians have different gut microbiota from ordinary elderly people. The core microbiome of centenarians in various countries has shown some common characteristics, which are worth further exploration. In this review, the significance of the human gut microbiota to health is briefly discussed, and the characteristics of the gut microbiota of long-lived senior persons of different ages and in different countries are described. Moreover, this review lists dietary interventions and fecal microbiota transplantation. In the end, it discusses the pros and cons of using probiotics to enhance the health of seniors through focused management of the gut microbiota. It aims to pave the way for further investigation into the nexus between gut microbiota, probiotics, and longevity, and then to reveal the underlying mechanism to promote longevity. KEY POINTS: • Gut microbial structure in different age groups and the characteristics of gut microbiota in centenarians. • Dietary interventions, fecal transplants, and probiotics target the modulation of gut microbiota for healthy aging.}, }
@article {pmid35882293, year = {2022}, author = {Luo, L and Luo, J and Cai, Y and Fu, M and Li, W and Shi, L and Liu, J and Dong, R and Xu, X and Tu, L and Yang, Y}, title = {Inulin-type fructans change the gut microbiota and prevent the development of diabetic nephropathy.}, journal = {Pharmacological research}, volume = {183}, number = {}, pages = {106367}, doi = {10.1016/j.phrs.2022.106367}, pmid = {35882293}, issn = {1096-1186}, mesh = {Animals ; Bacteria/metabolism ; *Diabetes Mellitus ; *Diabetic Nephropathies/drug therapy/prevention &amp; control ; Fatty Acids, Volatile/metabolism ; Fructans/pharmacology/therapeutic use ; *Gastrointestinal Microbiome ; Inulin/metabolism/therapeutic use ; Mice ; }, abstract = {Diabetic nephropathy (DN) is the most common cause of end-stage renal disease, and few treatment options that prevent the progressive loss of renal function are available. Studies have shown that dietary fiber intake improves kidney diseases and metabolism-related diseases, most likely through short-chain fatty acids (SCFAs). The present study aimed to examine the protective effects of inulin-type fructans (ITFs) on DN through 16 S rRNA gene sequencing, gas chromatographymass spectrometry (GCMS) analysis and fecal microbiota transplantation (FMT). The results showed that ITFs supplementation protected against kidney damage in db/db mice and regulated the composition of the gut microbiota. Antibiotic treatment and FMT experiments further demonstrated a key role of the gut microbiota in mediating the beneficial effects of ITFs. The ITFs treatment-induced changes in the gut microbiota led to an enrichment of SCFA-producing bacteria, especially the genera Akkermansia and Candidatus Saccharimonas, which increased the fecal and serum acetate concentrations. Subsequently, acetate supplementation improved glomerular damage and renal fibrosis by attenuating mitochondrial dysfunction and reducing toxic glucose metabolite levels. In conclusion, ITFs play a renoprotective role by modulating the gut microbiota and increasing acetate production. Furthermore, acetate mediates renal protection by regulating glucose metabolism, decreasing glycotoxic product levels and improving mitochondrial function.}, }
@article {pmid35881124, year = {2022}, author = {Slomski, A}, title = {Durable IBS Response From Fecal Microbiota Transplant.}, journal = {JAMA}, volume = {328}, number = {4}, pages = {322}, doi = {10.1001/jama.2022.12179}, pmid = {35881124}, issn = {1538-3598}, mesh = {*Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/microbiology/therapy ; }, }
@article {pmid35879237, year = {2022}, author = {Manning, L and Gosbell, IB and Howden, B and Tong, S}, title = {The demand-supply gap for faecal microbiota transplantation in Australia and New Zealand: a survey of infectious diseases physicians.}, journal = {Internal medicine journal}, volume = {52}, number = {7}, pages = {1282-1283}, doi = {10.1111/imj.15845}, pmid = {35879237}, issn = {1445-5994}, mesh = {*Communicable Diseases ; Fecal Microbiota Transplantation ; Humans ; New Zealand ; *Physicians ; Surveys and Questionnaires ; }, }
@article {pmid35879048, year = {2022}, author = {Haifer, C and Luu, LDW and Paramsothy, S and Borody, TJ and Leong, RW and Kaakoush, NO}, title = {Microbial determinants of effective donors in faecal microbiota transplantation for UC.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2022-327742}, pmid = {35879048}, issn = {1468-3288}, abstract = {OBJECTIVE: Faecal microbiota transplantation (FMT) has variable efficacy in treating UC. Recently, oral lyophilised FMT was found to induce remission in patients with UC, with one donor having 100% efficacy compared with a second donor (36% efficacy). We characterised differences in the gut microbiota of these two donors with the aim of improving FMT donor selection.<br><br>DESIGN: Faecal samples from the two donors were collected over a period of 44 (donor 1) or 70 (donor 2) weeks. The microbiome and metabolome were profiled using shotgun metagenomics and untargeted metabolomics RESULTS: Gut microbiome long-term stability was highly evident in the effective donor. Donor microbiota species evenness was a robust feature associated with clinical efficacy across two clinical trials of FMT in UC, leading to increased donor species engraftment in patients. Alpha diversity and beta diversity of donor gut microbiotas significantly differed. 90 bacterial species and one archaeon were differentially abundant between donors, 44 of which were >0.1% in relative abundance. 17/44 species were enriched in the effective donor, 11 of which (64.7%) were assembled into high-quality genomes that were prevalent (&#x2265;75% samples) in that donor, and six showed evidence of engraftment in patients. Taxonomic differences between donors translated to substantial microbial functional differences that were validated using metabolomics.<br><br>CONCLUSION: Donor microbiota stability and species evenness were identified as novel metrics that were associated with therapeutic efficacy in UC, beyond individual microbial species or metabolites. These metrics may represent community resilience that translates to better engraftment in the host.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12619000611123.}, }
@article {pmid35878341, year = {2022}, author = {Marclay, M and Dwyer, E and Suchodolski, JS and Lidbury, JA and Steiner, JM and Gaschen, FP}, title = {Recovery of Fecal Microbiome and Bile Acids in Healthy Dogs after Tylosin Administration with and without Fecal Microbiota Transplantation.}, journal = {Veterinary sciences}, volume = {9}, number = {7}, pages = {}, pmid = {35878341}, issn = {2306-7381}, support = {2018 IDEXX/CGS Veterinary Student Summer Scholar Award//Comparative Gastroenterology Society/ ; 2019//Hunter Retriever Club Foundation/ ; }, abstract = {Antibiotics cause gut dysbiosis and bile acid dysmetabolism in dogs. The effect of fecal microbiota transplantation (FMT) on microbiome and metabolome recovery is unknown. This prospective, randomized, placebo-controlled study included sixteen healthy purpose-bred dogs. All dogs received tylosin 20 mg/kg PO once daily (days 1-7) and were randomly assigned to either receive one FMT via enema (day 8), daily oral FMT capsules (days 8-21), or daily placebo capsules (days 8-21). Fecal samples were frozen at regular intervals until day 42. Quantitative PCR for 8 bacterial taxa was performed to calculate the fecal dysbiosis index (FDI) and fecal concentrations of unconjugated bile acids (UBA) were measured using gas chromatography-mass spectrometry. Tylosin altered the abundance of most evaluated bacteria and induced a significant decrease in secondary bile acid concentrations at day 7 in all dogs. However, most parameters returned to their baseline by day 14 in all dogs. In conclusion, tylosin markedly impacted fecal microbiota and bile acid concentrations, although return to baseline values was quick after the antibiotic was discontinued. Overall, FMT did not accelerate recovery of measured parameters. Further studies are warranted to confirm the value of FMT in accelerating microbiota recovery in antibiotic-associated dysbiosis in dogs.}, }
@article {pmid35877737, year = {2022}, author = {You, H and Deng, X and Bai, Y and He, J and Cao, H and Che, Q and Guo, J and Su, Z}, title = {The Ameliorative Effect of COST on Diet-Induced Lipid Metabolism Disorders by Regulating Intestinal Microbiota.}, journal = {Marine drugs}, volume = {20}, number = {7}, pages = {}, pmid = {35877737}, issn = {1660-3397}, mesh = {Animals ; Bacteria ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Lipid Metabolism ; *Lipid Metabolism Disorders ; Mice ; Mice, Inbred C57BL ; Sugars ; }, abstract = {BACKGROUND: Chitosan oligosaccharides, with an average molecular weight ≤ 1000 Da (COST), is a natural marine product that has the potential to improve intestinal microflora and resist lipid metabolism disorders.<br><br>METHODS: First, by establishing a mice model of lipid metabolism disorder induced by a high fat and high sugar diet, it is proven that COST can reduce lipid metabolism disorder, which may play a role in regulating intestinal microorganisms. Then, the key role of COST in the treatment of intestinal microorganisms is further confirmed through the method of COST-treated feces and fecal bacteria transplantation.<br><br>CONCLUSIONS: intestinal microbiota plays a key role in COST inhibition of lipid metabolism disorder induced by a high fat and high sugar diet. In particular, COST may play a central regulatory role in microbiota, including Bacteroides, Akkermansia, and Desulfovibrio. Taken together, our work suggests that COST may improve the composition of gut microbes, increase the abundance of beneficial bacteria, improve lipid metabolism disorders, and inhibit the development of metabolic disorders.}, }
@article {pmid35877603, year = {2022}, author = {Xian, W and Yang, S and Deng, Y and Yang, Y and Tan, Z and Li, W and Yang, R}, title = {Potential of Establishing the Corresponding Human Microbial Community in Pseudo Germ-Free Mice through Fecal Microbe Transfer from Three Urolithin Metabotypes.}, journal = {Journal of agricultural and food chemistry}, volume = {70}, number = {30}, pages = {9388-9398}, doi = {10.1021/acs.jafc.2c02796}, pmid = {35877603}, issn = {1520-5118}, mesh = {*Actinobacteria ; Animals ; Coumarins ; Ellagic Acid ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Mice ; *Microbiota ; }, abstract = {Three urolithin metabotypes (UMs) have been defined in the population according to final urolithins converted by gut microbiota. Currently, it is difficult to establish the cause-and-effect relationship between urolithins and microbiota in human studies. Studies on the health effects of ellagic acid (EA) in animal models rarely consider the differences in the urolithin production. Therefore, the objective of this study is to establish human microbiota-associated (HMA) mice, imitating the microbiota composition of the three UMs. Antibiotic-induced pseudo germ-free mice were gavaged with fecal bacteria of the three UM donors for four weeks. The results showed that the ability to produce corresponding urolithins was successfully transferred from the donor of the three UMs to HMA mice. The three UM HMA mice adopted a humanized microbiota profile similar to their corresponding donor. The family Eggerthellaceae and genera Eggerthella and Gordonibacter were successfully transferred and colonized from UM-A/B donors to HMA mice. Overall, the three UM HMA mouse models were successfully established, which provide a basis for exploring the health effects of EA.}, }
@article {pmid35877085, year = {2022}, author = {Thakur, PS and Aggarwal, D and Takkar, B and Shivaji, S and Das, T}, title = {Evidence Suggesting the Role of Gut Dysbiosis in Diabetic Retinopathy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {63}, number = {8}, pages = {21}, pmid = {35877085}, issn = {1552-5783}, support = {/WT_/Wellcome Trust/United Kingdom ; IA/CRC/19/1/610010//DBT Wellcome Trust India Alliance/ ; }, mesh = {*Diabetes Mellitus ; *Diabetic Retinopathy/epidemiology ; Dysbiosis ; Ecosystem ; *Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; }, abstract = {PURPOSE: Gut dysbiosis has been identified and tested in human trials for its role in diabetes mellitus (DM). The gut-retina axis could be a potential target for retardation of diabetic retinopathy (DR), a known complication of DM. This study reviews the evidence suggesting gut dysbiosis in DR.<br><br>METHODS: The published literature in the past 5 years was reviewed using predetermined keywords and articles. The review intended to determine changes in gut microbiome in DR, the hypothesized mechanisms linking to the gut-retina axis, its predictive potential for progression of DR, and the possible therapeutic targets.<br><br>RESULTS: The gut microbiota of people with DM differ from those without it, and the gut microbiota of people with DR differ from those without it. The difference is more significant in the former (DM versus no DM) and less significant in the latter (DM without DR versus DM with DR). Early research has suggested mechanisms of the gut-retina axis, but these are not different from known changes in the gut microbiome of people with DM. The current evidence on the predictive value of the gut microbiome in the occurrence and progression of DR is low. Therapeutic avenues targeting the gut-retina axis include lifestyle changes, pharmacologic inhibitors, probiotics, and fecal microbiota transplantation.<br><br>CONCLUSIONS: Investigating the therapeutic utility of the gut ecosystem for DM and its complications like DR is an emerging area of research. The gut-retina axis could be a target for retardation of DR but needs longitudinal regional studies adjusting for dietary habits.}, }
@article {pmid35876289, year = {2022}, author = {Sindhunata, DP and Meijnikman, AS and Gerdes, VEA and Nieuwdorp, M}, title = {Dietary fructose as a metabolic risk factor.}, journal = {American journal of physiology. Cell physiology}, volume = {323}, number = {3}, pages = {C847-C856}, doi = {10.1152/ajpcell.00439.2021}, pmid = {35876289}, issn = {1522-1563}, mesh = {Diet/adverse effects ; *Fructose/adverse effects/metabolism ; Humans ; Liver/metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism ; Risk Factors ; }, abstract = {Over the past decades, the role of the intestinal microbiota in metabolic diseases has come forward. In this regard, both composition and function of our intestinal microbiota is highly variable and influenced by multiple factors, of which diet is one of the major elements. Between 1970 and 1990, diet composition has changed and consumption of dietary sugars has increased, of which fructose intake rose by more than 10-fold. This increased intake of sugars and fructose is considered as one of the major risk factors in the developments of obesity and several metabolic disturbances. In this review, we describe the association of dietary fructose intake with insulin resistance, nonalcoholic fatty liver disease (NAFLD) and lipid metabolism. Moreover, we will focus on the potential causality of this altered gut microbiota using fecal transplantation studies in human metabolic disease and whether fecal microbial transplant can reverse this phenotype.}, }
@article {pmid35875536, year = {2022}, author = {Wang, X and Xing, Y and Ji, Y and Xi, H and Liu, X and Yang, L and Lei, L and Han, W and Gu, J}, title = {The Combination of Phages and Faecal Microbiota Transplantation Can Effectively Treat Mouse Colitis Caused by Salmonella enterica Serovar Typhimurium.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {944495}, pmid = {35875536}, issn = {1664-302X}, abstract = {Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the common causes of human colitis. In the present study, two lytic phages vB_SenS-EnJE1 and vB_SenS-EnJE6 were isolated and the therapeutic effect of the combination of phages and faecal microbiota transplantation (FMT) on S. Typhimurium-induced mouse colitis was investigated. The characteristics and genome analysis indicated that they are suitable phages for phage therapy. Results showed that vB_SenS-EnJE1 lysis 41/54 Salmonella strains of serotype O4, and vB_SenS-EnJE6 lysis 46/54 Salmonella strains of serotypes O4 and O9. Severe inflammatory symptoms and disruption of the intestinal barrier were observed in S. Typhimurium -induced colitis. Interestingly, compared with a single phage cocktail (Pc) or single FMT, the combination of Pc and FMT (PcFMT) completely removed S. Typhimurium after 72 h of treatment, and significantly improved pathological damage and restored the intestinal barrier. Furthermore, PcFMT effectively restored the intestinal microbial diversity, especially for Firmicutes/Bacteroidetes [predominantly bacterial phyla responsible for the production of short-chain fatty acids (SCFA)]. Additionally, we found that PcFMT treatment significantly increased the levels of SCFA. All these data indicated that the combination of phages and FMT possesses excellent therapeutic effects on S. Typhimurium -induced intestinal microbiota disorder diseases. Pc and FMT played roles in "eliminating pathogens" and "strengthening vital qi," respectively. This study provides a new idea for the treatment of intestinal microbiota disorder diseases caused by specific bacterial infections.}, }
@article {pmid35874759, year = {2022}, author = {Sen, T and Thummer, RP}, title = {The Impact of Human Microbiotas in Hematopoietic Stem Cell and Organ Transplantation.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {932228}, pmid = {35874759}, issn = {1664-3224}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Hematopoietic Stem Cells ; Humans ; *Microbiota ; *Organ Transplantation/adverse effects ; }, abstract = {The human microbiota heavily influences most vital aspects of human physiology including organ transplantation outcomes and transplant rejection risk. A variety of organ transplantation scenarios such as lung and heart transplantation as well as hematopoietic stem cell transplantation is heavily influenced by the human microbiotas. The human microbiota refers to a rich, diverse, and complex ecosystem of bacteria, fungi, archaea, helminths, protozoans, parasites, and viruses. Research accumulating over the past decade has established the existence of complex cross-species, cross-kingdom interactions between the residents of the various human microbiotas and the human body. Since the gut microbiota is the densest, most popular, and most studied human microbiota, the impact of other human microbiotas such as the oral, lung, urinary, and genital microbiotas is often overshadowed. However, these microbiotas also provide critical and unique insights pertaining to transplantation success, rejection risk, and overall host health, across multiple different transplantation scenarios. Organ transplantation as well as the pre-, peri-, and post-transplant pharmacological regimens patients undergo is known to adversely impact the microbiotas, thereby increasing the risk of adverse patient outcomes. Over the past decade, holistic approaches to post-transplant patient care such as the administration of clinical and dietary interventions aiming at restoring deranged microbiota community structures have been gaining momentum. Examples of these include prebiotic and probiotic administration, fecal microbial transplantation, and bacteriophage-mediated multidrug-resistant bacterial decolonization. This review will discuss these perspectives and explore the role of different human microbiotas in the context of various transplantation scenarios.}, }
@article {pmid35873830, year = {2022}, author = {Sun, X and Xue, L and Wang, Z and Xie, A}, title = {Update to the Treatment of Parkinson's Disease Based on the Gut-Brain Axis Mechanism.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {878239}, pmid = {35873830}, issn = {1662-4548}, abstract = {Gastrointestinal (GI) symptoms represented by constipation were significant non-motor symptoms of Parkinson's disease (PD) and were considered early manifestations and aggravating factors of the disease. This paper reviewed the research progress of the mechanism of the gut-brain axis (GBA) in PD and discussed the roles of α-synuclein, gut microbiota, immune inflammation, neuroendocrine, mitochondrial autophagy, and environmental toxins in the mechanism of the GBA in PD. Treatment of PD based on the GBA theory has also been discussed, including (1) dietary therapy, such as probiotics, vitamin therapy, Mediterranean diet, and low-calorie diet, (2) exercise therapy, (3) drug therapy, including antibiotics; GI peptides; GI motility agents, and (4) fecal flora transplantation can improve the flora. (5) Vagotomy and appendectomy were associated but not recommended.}, }
@article {pmid35873640, year = {2022}, author = {Liu, QH and Ke, X and Xiao, C}, title = {Current Applications of Fecal Microbiota Transplantation in Functional Constipation.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2022}, number = {}, pages = {7931730}, pmid = {35873640}, issn = {1741-427X}, abstract = {Functional constipation (FC) is a common condition that would be hard to treat in clinical practice with a prevalence incidence in the population. Pharmacotherapy is a common treatment modality. However, clinical effects are limited and patients continue to suffer from it. In recent years, with the gradual increase in research on gut microbiota, it is understood that dysbiosis of the gut microbiota is importantly associated with the development of constipation. Recent studies have shown that fecal microbiota transplantation (FMT) is an effective method for restoring gut microbiota, as well as being efficacious in the treatment of FC. This mini review explains the characteristics of gut microbiota in FC patients, the mechanism of action of FMT, treatment modalities, current efficacy, and related problems. The purpose is to provide research directions and references for the future applications of FMT in FC.}, }
@article {pmid35873168, year = {2022}, author = {Bu, F and Yao, X and Lu, Z and Yuan, X and Chen, C and Li, L and Li, Y and Jiang, F and Zhu, L and Shi, G and Chen, Y}, title = {Pathogenic or Therapeutic: The Mediating Role of Gut Microbiota in Non-Communicable Diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {906349}, pmid = {35873168}, issn = {2235-2988}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Noncommunicable Diseases/prevention &amp; control ; }, abstract = {Noncommunicable diseases (NCDs) lead to 41 million deaths every year and account for 71% of all deaths worldwide. Increasing evidence indicates that gut microbiota disorders are closely linked to the occurrence and development of diseases. The gut microbiota, as a potential transmission medium, could play a key role in the transmission and treatment of diseases. The gut microbiota makes noncommunicable diseases communicable. New methods of the prevention and treatment of these diseases could be further explored through the gut microbiota.}, }
@article {pmid35871602, year = {2022}, author = {Li, L and Wang, M and Bao, J and Wang, N and Huang, Y and He, S and Chen, B and Yan, F}, title = {Periodontitis may impair the homeostasis of systemic bone through regulation of gut microbiota in ApoE[-/-] mice.}, journal = {Journal of clinical periodontology}, volume = {49}, number = {12}, pages = {1304-1319}, doi = {10.1111/jcpe.13708}, pmid = {35871602}, issn = {1600-051X}, support = {CXTDB2017014//Project of Invigorating Health Care through Science, Technology and Education/ ; 2019060009//Nanjing Clinical Research Center for Oral Diseases/ ; 81970939//National Natural Science Foundation Project of China/ ; }, mesh = {Animals ; Mice ; *Alveolar Bone Loss ; Anti-Bacterial Agents/pharmacology ; Apolipoproteins E/metabolism ; Biomarkers/metabolism ; *Gastrointestinal Microbiome ; Homeostasis ; Osteoclasts ; Osteoprotegerin/metabolism ; *Periodontitis/metabolism ; RANK Ligand/metabolism ; Mice, Knockout, ApoE ; }, abstract = {AIM: To investigate whether periodontitis impacts bone homeostasis via gut microbiota regulation.<br><br>MATERIALS AND METHODS: Experimental periodontitis was induced by ligatures (LIG group). ApoE[-/-] mice were employed as a model with weakened bone homeostasis. Bone turnover was evaluated through micro-computerized tomography, haematoxylin and eosin-stained sections, osteoblast and osteoclast biomarkers in the bone and serum. Gut microbiota was analysed through 16S ribosomal RNA gene sequencing. Serum concentrations of cytokines were detected by enzyme-linked immunosorbent assay. The role of gut microbiota was evaluated through their transplantation into antibiotic-treated mice.<br><br>RESULTS: Periodontitis significantly increased the number of osteoclasts and the expression of the osteoclast biomarkers in the proximal tibia of ApoE[-/-] mice, with the RANKL/OPG (receptor activator of nuclear factor-&#x3ba;B ligand/osteoprotegerin) ratio significantly increased, which indicated the osteoclastic activity overwhelmed osteogenesis. Meanwhile, periodontitis altered the composition of gut microbiota and induced low-grade inflammation in the colon and blood circulation. Interestingly, the concentration of circulating tumour necrosis factor-&#x3b1;, interleukin (IL)-6, IL-1&#x3b2;, IL-17A, and monocyte chemotactic factor-1 were positively correlated with faecal &#x3b1;1-antitrypsin and calprotectin, as well as serum OPG and RANKL. Furthermore, transplantation of gut microbiota from mice with periodontitis to antibiotic-treated mice could partially re-capitulate the phenotypes in the bone and colon.<br><br>CONCLUSION: Periodontitis may impair systemic bone homeostasis through gut microbiota.}, }
@article {pmid35871158, year = {2023}, author = {Yendrapalli, U and Edwards, J and Belk, M and Steuber, T and Hassoun, A}, title = {Efficacy and safety of commercialized fecal microbiota transplant for the treatment of recurrent Clostridioides difficile infection.}, journal = {Infection, disease &amp; health}, volume = {28}, number = {1}, pages = {71-73}, doi = {10.1016/j.idh.2022.06.002}, pmid = {35871158}, issn = {2468-0869}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; Feces ; }, }
@article {pmid35869860, year = {2022}, author = {Zhao, Z and Ji, X and Zhang, T and Li, Q and Marcella, C and Wen, Q and Cui, B and Zhang, F}, title = {Washed microbiota transplantation improves the fertility of patients with inflammatory bowel disease.}, journal = {Chinese medical journal}, volume = {135}, number = {12}, pages = {1489-1491}, pmid = {35869860}, issn = {2542-5641}, mesh = {Fecal Microbiota Transplantation ; Fertility ; Humans ; *Inflammatory Bowel Diseases/surgery ; *Microbiota ; }, }
@article {pmid35869296, year = {2022}, author = {Graham, F}, title = {Daily briefing: How faecal transplants could boost cancer treatments.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-022-02030-1}, pmid = {35869296}, issn = {1476-4687}, }
@article {pmid35868631, year = {2022}, author = {Hamidi Nia, L and Claesen, J}, title = {Engineered Cancer Targeting Microbes and Encapsulation Devices for Human Gut Microbiome Applications.}, journal = {Biochemistry}, volume = {61}, number = {24}, pages = {2841-2848}, pmid = {35868631}, issn = {1520-4995}, support = {P30 CA043703/CA/NCI NIH HHS/United States ; R01 AI153173/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota ; *Colonic Neoplasms ; Bacteria/metabolism ; Hydrogels/metabolism ; }, abstract = {The gut microbiota produce specialized metabolites that are important for maintaining host health homeostasis. Hence, unstable production of these metabolites can contribute to diseases such as inflammatory bowel disease and colon cancer. While fecal transplantation or dietary modification approaches can be used to correct the gut microbial community's metabolic output, this Perspective focuses on the use of engineered bacteria. We highlight recent advances in bacterial synthetic biology approaches for the treatment of colorectal cancer and systemic tumors and discuss the functionality and biochemical properties of novel containment approaches using hydrogel-based and electronic devices. Synthetic circuitry refinement and incorporation of novel functional modules have enabled more targeted detection of colonic tumors and delivery of anticancer compounds inside the gastrointestinal (GI) tract, as well as the design of tumor-homing bacteria capable of recruiting infiltrating T cells. Engineering challenges in these applications include the stability of the genetic circuits, long-term engraftment of the chosen chassis, and containment of the synthetic microbes' activity to the diseased tissues. Hydrogels are well-suited to the encapsulationo of living organisms due to their matrix structure and tunable porosity. The matrix structure allows a dried hydrogel to collect and contain GI contents. Engineered bacteria that sense GI tract inflammation or tumors and release bioactive metabolites to the targeted area can be encapsulated. Electronic devices can be enabled with additional measuring and data processing capabilities. We expect that engineered devices will become more important in the containment and delivery of synthetic microbes for diagnostic and therapeutic applications.}, }
@article {pmid35868075, year = {2022}, author = {Hu, C and Liu, M and Sun, B and Tang, L and Zhou, X and Chen, L}, title = {Young fecal transplantation mitigates the toxicity of perfluorobutanesulfonate and potently refreshes the reproductive endocrine system in aged recipients.}, journal = {Environment international}, volume = {167}, number = {}, pages = {107418}, doi = {10.1016/j.envint.2022.107418}, pmid = {35868075}, issn = {1873-6750}, mesh = {Animals ; Endocrine System ; Fecal Microbiota Transplantation ; Fluorocarbons ; Gonadal Steroid Hormones/metabolism ; Reproduction ; Sulfonic Acids ; *Water Pollutants, Chemical/toxicity ; *Zebrafish/metabolism ; }, abstract = {The aging process leads to the gradual impairment of physiological functions in the elderly, making them more susceptible to the toxicity of environmental pollutants. In this study, aged zebrafish were first transplanted with the feces from young donors and subsequently exposed to perfluorobutanesulfonate (PFBS), an emerging persistent toxic pollutant. The interaction between young fecal transplant and PFBS inherent toxicity was investigated, focusing on reproductive performance and the underlying endocrine mechanism. The results showed that PFBS single exposure increased the percentage of primary oocytes in aged ovaries, implying a blockage of oogenesis. However, transplantation of young feces completely abolished the effects of PFBS and promoted oocyte growth, as inferred by the obviously lower percentage of primary oocytes, accompanied by a higher percentage of cortical-alveolar oocytes. Measurement of sex hormones found that PFBS significantly increased the blood concentration of estradiol and disrupted the balance of sex hormones in the elderly, which were, however, efficiently ameliorated by young fecal transplantation. Based on gene transcription along the hypothalamic-pituitary-gonadal axis, hierarchical clustering analysis showed similar profiles of the reproductive endocrine system between young zebrafish and their aged counterparts transplanted with young feces, implying that young fecal transplantation might refresh the endocrine system of aged recipients, regardless of PFBS exposure. The increased transcription levels of mRNAs encoding vitellogenin, activinBA, and membrane bound progestin receptors would cooperatively enhance the growth and maturation of oocytes in the ovaries of aged zebrafish receiving young fecal transplantation. Overall, the findings highlighted the potent efficacy of young fecal transplantation to improve the reproductive function of the elderly and to mitigate the endocrine disruption of an environmental pollutant. These findings are expected to broaden our understanding of the efficacy, mechanisms, and application of fecal transplantation.}, }
@article {pmid35864969, year = {2022}, author = {Liu, Z and Li, C and Liu, M and Song, Z and Moyer, MP and Su, D}, title = {The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/β-catenin Pathway.}, journal = {International journal of biological sciences}, volume = {18}, number = {11}, pages = {4469-4481}, pmid = {35864969}, issn = {1449-2288}, mesh = {Animals ; *Colitis/chemically induced/drug therapy ; *Gastrointestinal Microbiome ; Hypoxia ; Low Density Lipoprotein Receptor-Related Protein-6/genetics/metabolism ; Mice ; *Wnt Signaling Pathway ; beta Catenin/genetics/metabolism ; }, abstract = {Our study is to explore the key molecular of Low-density lipoprotein receptor-related protein 6 (LRP6) and the related Wnt/β-catenin pathway regulated by LRP6 during the intestinal barrier dysfunction. Colorectal protein profile analysis showed that LRP6 expression was decreased in dextran sulfate sodium (DSS)-induced colitis mice, and mice received fecal bacteria transplantation from stroke patients. Mice with intestinal hypoxia and intestinal epithelial cells cultured in hypoxia showed decreased expression of LRP6. Overexpression of LPR6 or its N-terminus rescued the Wnt/β-catenin signaling pathway which was inhibited by hypoxia and endoplasmic reticulum stress. In mice overexpressing of LRP6, the expression of β-catenin and DKK1 increased, Bcl2 decreased, and Bax increased. Mice with LRP6 knockout showed an opposite trend, and the expression of Claudin2, Occludin and ZO-1 decreased. Two drugs, curcumin and auranofin could alleviate intestinal barrier damage in DSS-induced colitis mice by targeting LRP-6. Therefore, gut microbiota dysbiosis and hypoxia can inhibit the LRP6 and Wnt/β-catenin pathway, and drugs targeting LRP6 can protect the intestinal barrier.}, }
@article {pmid35862958, year = {2022}, author = {Miao, X and Jiang, Y and Kong, D and Wu, Z and Liu, H and Ye, X and Gong, W}, title = {Lactobacillus rhamnosus HN001 Ameliorates BEZ235-Induced Intestinal Dysbiosis and Prolongs Cardiac Transplant Survival.}, journal = {Microbiology spectrum}, volume = {10}, number = {4}, pages = {e0079422}, pmid = {35862958}, issn = {2165-0497}, mesh = {Animals ; *Dysbiosis/therapy ; *Heart Transplantation ; *Imidazoles/adverse effects ; *Lacticaseibacillus rhamnosus/metabolism ; Mice ; Phosphoinositide-3 Kinase Inhibitors/adverse effects ; *Quinolines/adverse effects ; RNA, Ribosomal, 16S/genetics ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {Cardiac allograft rejection remains a major factor limiting long-term engraftment after transplantation. A novel phosphoinositide 3-kinase (PI3K)/mTOR dual inhibitor, BEZ235, prolonged cardiac allograft survival by effectively suppressing activation of the PI3K/serine/threonine kinase (AKT)/mTOR pathway. However, long-term usage of pharmacological immunosuppressant drugs can cause intestinal microbiota dysbiosis. We established mouse models of allogeneic heterotopic heart transplantation with different treatments. Fecal samples were collected and subjected to 16S rRNA sequencing and targeted fecal metabolomic analysis. Graft samples were taken for immune cell detection by flow cytometry. Inflammatory cytokines in serum were quantified by enzyme-linked immunosorbent assay (ELISA). Compared to single-target approaches (IC-87114 and rapamycin), BEZ235 more efficiently prolongs cardiac transplant survival. Interestingly, BEZ235 reduces the diversity and abundance of the intestinal microbiota community. We demonstrated that Lactobacillus rhamnosus HN001 rescues the intestinal microbiota imbalance induced by BEZ235. IMPORTANCE Our data confirmed that the combination of BEZ235 and Lactobacillus rhamnosus HN001 significantly prolongs cardiac transplant survival. A main metabolic product of Lactobacillus rhamnosus HN001, propionic acid (PA), enriches regulatory T (Treg) cells and serves as a potent immunomodulatory supplement to BEZ235. Our study provides a novel and efficient therapeutic strategy for transplant recipients.}, }
@article {pmid35860380, year = {2022}, author = {Xue, L and Deng, Z and Luo, W and He, X and Chen, Y}, title = {Effect of Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {759306}, pmid = {35860380}, issn = {2235-2988}, mesh = {Dysbiosis/etiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Non-alcoholic Fatty Liver Disease/etiology/therapy ; Obesity/complications/therapy ; }, abstract = {BACKGROUND AND AIMS: The clinical efficacy of fecal microbiota transplantation (FMT) in patients with non-alcoholic fatty liver disease (NAFLD) and the variant effects of FMT on lean and obese NAFLD patients remain elusive. Our study aimed to determine the clinical efficacy and safety of FMT for patients with NAFLD, elucidating its different influences on lean and obese patients with NAFLD.<br><br>METHODS: We performed a randomized and controlled clinical trial. Patients in the non-FMT group were administered oral probiotics. In the FMT group, patients were randomized to receive FMT with donor stool (heterologous) via colonoscopy, followed by three enemas over 3 days. Both groups were also required to maintain a healthy diet and keep regular exercise for more than 40 min every day. They returned to the hospital for reexamination 1 month after treatment.<br><br>RESULTS: FMT can decrease the fat accumulation in the liver by improving the gut microbiota dysbiosis, thus attenuating fatty liver disease. Significant differences in the clinical features and gut microbiota between lean and obese NAFLD patients were unveiled. Moreover, FMT had better effects on gut microbiota reconstruction in lean NAFLD than in obese NAFLD patients.<br><br>CONCLUSIONS: FMT could successfully improve the therapeutic effects on patients with NAFLD, and its clinical efficacy was higher in lean NAFLD than in obese NAFLD patients.}, }
@article {pmid35860242, year = {2022}, author = {Du, HX and Yue, SY and Niu, D and Liu, C and Zhang, LG and Chen, J and Chen, Y and Guan, Y and Hua, XL and Li, C and Chen, XG and Zhang, L and Liang, CZ}, title = {Gut Microflora Modulates Th17/Treg Cell Differentiation in Experimental Autoimmune Prostatitis via the Short-Chain Fatty Acid Propionate.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {915218}, pmid = {35860242}, issn = {1664-3224}, mesh = {Animals ; Cell Differentiation ; *Chronic Pain ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Pelvic Pain/metabolism ; Propionates/pharmacology ; *Prostatitis ; RNA, Ribosomal, 16S ; T-Lymphocytes, Regulatory/metabolism ; }, abstract = {Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a very common urological disorder and has been gradually regarded as an immune-mediated disease. Multiple studies have indicated that the gut microflora plays a pivotal part in immune homeostasis and autoimmune disorder development. However, whether the gut microflora affects the CP/CPPS, and the underlying mechanism behind them remain unclear. Here, we built an experimental autoimmune prostatitis (EAP) mouse model by subcutaneous immunity and identified that its Th17/Treg frequency was imbalanced. Using fecal 16s rRNA sequencing and untargeted/targeted metabolomics, we discovered that the diversity and relative abundance of gut microflora and their metabolites were obviously different between the control and the EAP group. Propionic acid, a kind of short-chain fatty acid (SCFA), was decreased in EAP mice compared to that in controls, and supplementation with propionic acid reduced susceptibility to EAP and corrected the imbalance of Th17/Treg cell differentiation in vivo and in vitro. Furthermore, SCFA receptor G-protein-coupled receptor 43 and intracellular histone deacetylase 6 regulated by propionic acid in Th17 and Treg cells were also evaluated. Lastly, we observed that fecal transplantation from EAP mice induced the decrease of Treg cell frequency in recipient mice. Our data showed that gut dysbiosis contributed to a Th17/Treg differentiation imbalance in EAP via the decrease of metabolite propionic acid and provided valuable immunological groundwork for further intervention in immunologic derangement of CP/CPPS by targeting propionic acid.}, }
@article {pmid35859811, year = {2022}, author = {Cerquetella, M and Marchegiani, A and Rossi, G and Trabalza-Marinucci, M and Passamonti, F and Isidori, M and Rueca, F}, title = {Case Report: Oral Fecal Microbiota Transplantation in a Dog Suffering From Relapsing Chronic Diarrhea-Clinical Outcome and Follow-Up.}, journal = {Frontiers in veterinary science}, volume = {9}, number = {}, pages = {893342}, pmid = {35859811}, issn = {2297-1769}, abstract = {The present case report describes the effects of orally administered fecal microbiota transplantation (FMT) (frozen capsules) in a dog suffering from relapsing chronic diarrhea, needing a continuous low prednisolone dose to maintain the condition under acceptable control. Through FMT, we aimed at evaluating the possibility of improving the clinical score and/or reducing/suspending steroid administration. During a first period of strict monitoring (21 days), the canine inflammatory bowel disease activity index (CIBDAI) score passed from mild to clinically insignificant disease. Furthermore, two additional gastrointestinal signs that had been reported, bloating and episodes of painful defecation, rapidly improved (bloating) or even resolved (painful defecation). The patient was then followed for 18 months (to the authors' knowledge, the longest follow-up time ever reported in a dog), during which no serious relapses occurred and no increase in prednisolone dose was necessary. No adverse clinical effects were ever reported during monitoring. The present description provides a further experience increasing those already present in the veterinary literature, in which an agreement on how to use FMT has not yet been achieved although strongly needed and recommended.}, }
@article {pmid35859583, year = {2022}, author = {Bao, P and Zhang, Z and Liang, Y and Yu, Z and Xiao, Z and Wang, Y and Yu, Y and Liu, W and Chen, X and Huang, Z and Su, Y and Chen, R and Ge, J}, title = {Role of the Gut Microbiota in Glucose Metabolism During Heart Failure.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {903316}, pmid = {35859583}, issn = {2297-055X}, abstract = {BACKGROUND: Blood glucose disorders are prevalent in heart failure, while the influence of the gut microbiota on this process remains unclear. Here, we used heart failure model mice and fecal microbiota transplantation (FMT) mice to evaluate the effect of the gut microbiota on the regulation of blood glucose during heart failure.<br><br>METHODS: Thoracic aortic constriction (TAC) surgery was performed in a heart failure model, while an antibiotic cocktail was used to eliminate the microbiota to establish a germ-free (GF) model. Blood glucose, insulin, and glucagon levels were measured, and an intraperitoneal glucose tolerance test (IPGTT) was performed. 16S rRNA sequencing and metabolomics were used to evaluate the changes in gut microbiota structure and metabolism induced by TAC. Another group of FMT mice was established to observe the effect of the gut microbiota on host metabolism.<br><br>RESULTS: After microbiota clearance, the glucagon concentration, the homeostasis model assessment for insulin resistance (HOMA-IR), and the area under the curve (AUC) of the IPGTT were decreased significantly in the TAC germ-free (TAC-GF) group in the third month as compared to the other groups. 16S rRNA sequencing indicated that TAC surgery affected the gut microbiota structure, and fecal metabolomics suggested that noradrenaline and adrenaline levels were higher in the TAC group than in the sham group. The FMT mice transplanted with the feces of the TAC (FMT-TAC) mice displayed a higher AUC of IPGTT, accompanied by a higher glucagon level, insulin level, and HOMA-IR than those of the mice in the other groups. The serum metabolomics of the FMT-TAC group showed that noradrenaline levels were significantly higher than those of the FMT-sham group.<br><br>CONCLUSION: The gut microbiota and its metabolism were altered during heart failure, which increased blood glucose and glucagon in the host.}, }
@article {pmid35857570, year = {2022}, author = {Leonardi, I}, title = {Beyond the gut.}, journal = {Science (New York, N.Y.)}, volume = {377}, number = {6602}, pages = {165}, doi = {10.1126/science.abq6056}, pmid = {35857570}, issn = {1095-9203}, mesh = {Animals ; *Candida/physiology ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Host-Pathogen Interactions ; Humans ; *Immunity ; Mice ; Microbial Interactions ; *Mycobiome/physiology ; }, abstract = {Mycobiota modulate immunity and behavior.}, }
@article {pmid35854629, year = {2022}, author = {He, R and Li, P and Wang, J and Cui, B and Zhang, F and Zhao, F}, title = {The interplay of gut microbiota between donors and recipients determines the efficacy of fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2100197}, pmid = {35854629}, issn = {1949-0984}, mesh = {Bacteria/genetics ; *Clostridioides difficile ; *Clostridium Infections/microbiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/microbiology ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising treatment for microbiota dysbiosis associated diseases, such as Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD). The engraftment of donor bacteria is essential for the effectiveness of FMT, which to some extent depends on the matching of donors and recipients. However, how different types of donor-derived bacteria affect FMT efficacy has not been fully dissected. We recruited two longitudinal IBD cohorts of 103 FMT recipients and further analyzed 1,280 microbiota datasets from 14 public CDI and IBD studies to uncover the effect of donor-derived microbiota in recipients. We found that two enterotypes, RCPT/E and RCPT/B (dominated by Enterobacteriaceae and Bacteroides, respectively), consistently exist in both CDI and IBD patients. Based on a time-course-based multi-cohort analysis of FMT fecal samples, we observed the interplay between recipient and donor-derived microbiota during FMT, in which the FMT outcome was significantly associated with the enterotype and microbiota distance between donor and recipient after FMT. We proposed a new measurement, the ratio of colonizers to residents after FMT (C2R), to quantify the engraftment of donor-derived bacteria in the recipients, and then constructed an enterotype-based statistical model for donor-recipient matching, which was validated by both cross-validation and an additional IBD FMT cohort (n = 42). We believe that with the accumulation of FMT multi-omics datasets, machine learning-based methods will be helpful for rational donor selection for improving efficacy and precision FMT practices.}, }
@article {pmid35849493, year = {2022}, author = {Jin, X and Liu, Y and Yan, W and Shi, S and Liu, L and Lin, B and Guo, X and Cai, T and Wei, Y}, title = {Gut microbiota from nCAL patients promotes colon anastomotic healing by inducing collagen synthesis in epithelial cells.}, journal = {Journal of gastroenterology and hepatology}, volume = {37}, number = {9}, pages = {1756-1767}, doi = {10.1111/jgh.15946}, pmid = {35849493}, issn = {1440-1746}, support = {81970466//National Natural Science Foundation of China/ ; }, mesh = {Anastomosis, Surgical/adverse effects ; Anastomotic Leak/etiology ; Animals ; Collagen/metabolism ; Colon/metabolism/surgery ; Epithelial Cells/metabolism ; *Gastrointestinal Microbiome ; Rats ; Transforming Growth Factor beta ; }, abstract = {BACKGROUND AND AIMS: Colon anastomotic leak (CAL) is considered one of the most feared and serious postoperative complications in colorectal cancer (CRC) patients, with no effective prevention strategies to date. Based on previous studies, gut microbiota is associated with anastomotic healing, but its ability to effectively promote anastomotic healing remains largely unknown.<br><br>METHODS: We performed a clinical study to analyze the gut microbiota profiling in CRC patients who developed CAL and those who did not (nCAL) using 16S-rRNA-based next-generation sequencing (NGS). To investigate these changes in an in vivo model, we performed fecal microbiota transplantation in a colon anastomosis rat experimental model to elucidate the causal effect between gut microbiota and anastomotic healing. Notably, RNA-seq in the anastomotic tissue of the latter experimental model was utilized to discover the potential molecular mechanism.<br><br>RESULTS: Our analysis implicated that gut microbiota profiling was profoundly different between CAL and nCAL patients. Strikingly, the rat experimental model transplanted with fecal microbiota derived from nCAL patients demonstrated enhanced anastomotic healing properties. Moreover, collagen synthesis, EMT, and TGF-&#x3b2;/Smad signaling pathways were upregulated in the same rats. Concordantly, we discovered that the better anastomotic healing profiling displayed in gut microbiota derived from nCAL patients is dependent on the TGF-&#x3b2;/Smad-induced EMT in vitro and in vivo.<br><br>CONCLUSIONS: Collectively, our clinical study identified the postoperative gut microbiota profile is associated with CAL in CRC patients. On the contrary, fecal microbiota from nCAL patients promotes anastomotic healing via TGF-&#x3b2;/Smad-induced EMT, with subsequent collagen synthesis and enhanced anastomosis healing.}, }
@article {pmid35847121, year = {2022}, author = {Xu, X and Ying, J}, title = {Gut Microbiota and Immunotherapy.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {945887}, pmid = {35847121}, issn = {1664-302X}, abstract = {The gut microbiota is the largest microbiota in the body, which is closely related to the immune state of the body. A number of studies have shown that gut microbiota and its metabolites are involved in host immune regulation. Immune checkpoint inhibitors have become an important drug for the treatment of many malignant tumors, which can significantly improve the prognosis of tumor patients. However, a considerable number of patients cannot benefit from immune checkpoint inhibitors. At present, the known treatment methods of microbiota manipulation mainly include fecal microbiota transplantation, dietary regulation, prebiotics and so on. Therefore, this paper will discuss the possibility of improving the anti-tumor efficacy of immunotherapy from the perspectives of the gut microbiota and immunotherapy.}, }
@article {pmid35847075, year = {2022}, author = {Bilinski, J and Dziurzynski, M and Grzesiowski, P and Podsiadly, E and Stelmaszczyk-Emmel, A and Dzieciatkowski, T and Lis, K and Tyszka, M and Ozieranski, K and Dziewit, &#x141; and Basak, GW}, title = {Fresh Versus Frozen Stool for Fecal Microbiota Transplantation-Assessment by Multimethod Approach Combining Culturing, Flow Cytometry, and Next-Generation Sequencing.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {872735}, pmid = {35847075}, issn = {1664-302X}, abstract = {The objective of this work was to compare the quality of FMT preparations made from fresh feces with those made from feces frozen at -30°C without any pre-processing or cryopreservation additives. The research hypothesis was that such preservation protocol (frozen whole stool, then thawed and processed) is equipotent to classical fresh FMT preparation. For that, three complementary methods were applied, including: (i) culturing in aerobic and anaerobic conditions, (ii) measuring viability by flow cytometry, and (iii) next-generation sequencing. Flow cytometry with cell staining showed that the applied freezing protocol causes significant changes in all of the observed bacterial fractions. Alive cell counts dropped four times, from around 70% to 15%, while the other two fractions, dead and unknown cell counts quadrupled and doubled, with the unknown fraction becoming the dominant one, with an average contribution of 57.47% per sample. It will be very interesting to uncover what this unknown fraction is (e.g., bacterial spores), as this may change our conclusions (if these are spores, the viability could be even higher after freezing). Freezing had a huge impact on the structure of cultivable bacterial communities. The biggest drop after freezing in the number of cultivable species was observed for Actinobacteria and Bacilli. In most cases, selected biodiversity indices were slightly lower for frozen samples. PCoA visualization built using weighted UniFrac index showed no donor-wise clusters, but a clear split between fresh and frozen samples. This split can be in part attributed to the changes in the relative abundance of Bacteroidales and Clostridiales orders. Our results clearly show that whole stool freezing without any cryoprotectants has a great impact on the cultivability and biodiversity of the bacterial community, and possibly also on the viability of bacterial cells.}, }
@article {pmid35846749, year = {2022}, author = {Chen, Z and Yang, B and Wang, Z and Rong, X and Zhu, Q and Guo, J}, title = {Modulation of the Gut Microbiota by Fufang-Zhenzhu-Tiaozhi Capsule Attenuates Hypertension Induced by a High-Fructose and High-Salt Diet.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {854849}, pmid = {35846749}, issn = {2235-2988}, mesh = {Animals ; Diet ; Drugs, Chinese Herbal ; Dysbiosis ; Fructose/pharmacology ; *Gastrointestinal Microbiome ; *Hypertension/drug therapy ; RNA, Ribosomal, 16S/genetics ; Rats ; }, abstract = {Hypertension is frequently comorbid with the disorders of glucose and lipid metabolism. The increased intakes of fructose and salt contribute to the development of hypertension and related metabolic disorders, which are closely associated with gut dysbiosis. Fufang-Zhenzhu-Tiaozhi capsule (FTZ), a traditional Chinese patent medicine commonly used in clinical practice, has recently emerged as a promising drug candidate for metabolic diseases. In this study, FTZ treatment is identified as attenuating blood pressure increase and improving the metabolism of lipid and uric acid in high-fructose and high-salt (HFS) diet-fed rats. FTZ also substantially alleviated renal fibrosis and the mRNA expression of inflammation cytokines, NADPH oxidases, and the renin-angiotensin system in the renal cortex. 16S rRNA sequencing of fecal samples revealed that FTZ restored HFS-induced gut dysbiosis, seen as increased intestinal microbial richness and diversity. Furthermore, fecal microbiota transplantation also achieved similar therapeutic effects and alterations in gut microbiota profile induced by FTZ. Taken together, this study highlights the efficacy of FTZ in attenuating HFS-induced hypertension and related metabolic disorders and renal injury. The antihypertensive effect is associated with the modulation of gut microbiota.}, }
@article {pmid35846232, year = {2022}, author = {Park, SS and Kim, SH and Kim, CJ and Shin, MS and Park, YJ and Kim, TW}, title = {Effects of exercise and microbiota transplant on the memory of obesity-induced mice.}, journal = {Journal of exercise rehabilitation}, volume = {18}, number = {3}, pages = {162-170}, pmid = {35846232}, issn = {2288-176X}, abstract = {This study attempted to investigate the association between changes in the intestinal environment and the brain using a model that received aerobic exercise and microbiome transplantation. All mice were fed a diet containing 60% fat. For the obesity with nonexercise microbiome transplantation group, feces from donors that did not undergo exercise were administered. For the obesity with exercise microbiome trans-plantation group, feces from donors who underwent exercise were administered. Treadmill exercise started 16 weeks after the intake of the high fat feeding and continued for 24 weeks. The short-term memory and spatial learning memory were determined by step-down avoidance test and Morris water maze task, immunohistochemistry for glial fibrillary acidic protein, western blot analysis for brain-derived neurotrophic factor and tropomyosin receptor kinase B were performed in the hippocampus. Exercise was the most effective way to reduce obesity, improve memory function, suppress inflammation, and increase brain-derived neurotrophic factor expression. Intestinal microbiota transplantation was the second most effective after exercise. However, there was no significant difference in the fecal microbiota transplant group according to whether or not exercise was performed.}, }
@article {pmid35843456, year = {2022}, author = {Wen, S and Zhao, Y and Liu, S and Yuan, H and You, T and Xu, H}, title = {Microplastics-perturbed gut microbiota triggered the testicular disorder in male mice: Via fecal microbiota transplantation.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {309}, number = {}, pages = {119789}, doi = {10.1016/j.envpol.2022.119789}, pmid = {35843456}, issn = {1873-6424}, mesh = {Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Male ; Mammals ; Mice ; *Microplastics ; Plastics/toxicity ; Polystyrenes ; }, abstract = {Microplastics (MPs), an emerging environmental pollutant, have been clarified to induce testicular disorder in mammals. And the current studies have delineated a correlation between gut microbiota and male reproduction. However, it's still unclear whether gut microbiota gets involved in MPs-induced reproductive toxicity. In this work, we constructed a mouse model drinking 5 μm polystyrene-MPs (PS-MPs) at the concentrations of 100 μg/L and 1000 μg/L for 90 days. Evident histological damage, spermatogenetic disorder and hormones synthesis inhibition were observed in PS-MPs exposed mice. With fecal microbiota transplantation (FMT) trial, the recipient mice exhibited gut microbial alteration, and the elevated abundance of Bacteroides and Prevotellaceae_UCG-001 were positively correlated with testicular disorder according to spearman correlation analysis. Mechanistically, increased proportion of pro-inflammatory bacteria may drive translocation of T helper 17 (Th17) cells, resulting in overproduced interleukin (IL)-17 A and downstream inflammatory response in both the mice exposed to PS-MPs and corresponding recipient mice. In summary, our findings revealed the critical role of gut microbiota in PS-MPs-induced reproductive toxicity, and tried to elucidate the underlying mechanism of gut microbial dysregulation-mediated IL-17 A signaling pathway. Furthermore, this study also provides the research basis for gut microbiota-targeted treatment of male infertility in the future.}, }
@article {pmid35842183, year = {2022}, author = {Guo, W and Zhang, Z and Li, L and Liang, X and Wu, Y and Wang, X and Ma, H and Cheng, J and Zhang, A and Tang, P and Wang, CZ and Wan, JY and Yao, H and Yuan, CS}, title = {Gut microbiota induces DNA methylation via SCFAs predisposing obesity-prone individuals to diabetes.}, journal = {Pharmacological research}, volume = {182}, number = {}, pages = {106355}, doi = {10.1016/j.phrs.2022.106355}, pmid = {35842183}, issn = {1096-1186}, mesh = {DNA Methylation ; *Diabetes Mellitus ; Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Humans ; Obesity/genetics/metabolism ; Propionates/pharmacology ; Tandem Mass Spectrometry ; }, abstract = {Obesity-prone (OP) individuals have a significant predisposition to obesity and diabetes. Previously, we have found that OP individuals, despite being normal in weight and BMI, have already exhibited diabetes-related DNA methylation signatures. However, the underlying mechanisms remain obscure. Here we determined the effects of gut microbiota on DNA methylation and investigated the underlying mechanism from microbial-derived short-chain fatty acids (SCFAs). Diabetes-related DNA methylation loci were screened and validated in a new OP cohort. Moreover, the OP group was revealed to have distinct gut microbiota compositions, and fecal microbiota transplantation (FMT) demonstrated the role of gut microbiota in inducing diabetes-related DNA methylations and glucolipid disorders. UPLC-ESI-MS/MS analysis indicated a significantly lower level of total fecal SCFAs in the OP group. The gut microbiota from OP subjects yielded markedly decreased total SCFAs, while notably enriched propionate. Additionally, propionate was also identified by variable importance in projection (VIP) score as the most symbolic SCFAs of the OP group. Further cellular experiments verified that propionate could induce hypermethylation at locus cg26345888 and subsequently inhibit the expression of the target gene DAB1, which was crucially associated with clinical vitamin D deficiency and thus may affect the development and progression of diabetes. In conclusion, our study revealed that gut microbiota-derived propionate induces specific DNA methylation, thus predisposing OP individuals to diabetes. The findings partially illuminate the mechanisms of diabetes susceptibility in OP populations, implying gut microbiota and SCFAs may serve as promising targets both for clinical treatment and medication development of diabetes.}, }
@article {pmid35841869, year = {2022}, author = {Li, X and Zhang, S and Guo, G and Han, J and Yu, J}, title = {Gut microbiome in modulating immune checkpoint inhibitors.}, journal = {EBioMedicine}, volume = {82}, number = {}, pages = {104163}, pmid = {35841869}, issn = {2352-3964}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Immunotherapy ; *Neoplasms/drug therapy ; }, abstract = {Gut microbiome has been increasingly recognized for its influence on a diverse array of human diseases including cancer, and may also influence the outcome of cancer therapies. A prime example is seen in immunotherapy, for which gut microbes determine the therapeutic responses associated with immune checkpoint inhibitors (ICIs) in preclinical models and patient cohorts. This evidence hints that inter-individual variations in the gut microbiota may account for the significant heterogeneity in immunotherapeutic responses to ICIs. Understanding the functional role of gut microbiome in regulating not only mucosal but also systemic immunity and cancer is critical to move forward in this era of precision medicine. What's more, microbiota can be modified via several different strategies that are essential for the efforts in expanding immunotherapy efficacy. This review summarizes latest knowledge about the interactions between microbiome, host immunity and cancer, and strategies to modulate the microbiome with implications to be translated into clinic. FUNDING: This study was supported by National Key R&amp;D Program of China (No. 2020YFA0509200/2020YFA0509203), RGC Theme-based Res Scheme Hong Kong (T21-705/20-N).}, }
@article {pmid35841835, year = {2022}, author = {Gao, Y and Ma, L and Su, J}, title = {Host and microbial-derived metabolites for Clostridioides difficile infection: Contributions, mechanisms and potential applications.}, journal = {Microbiological research}, volume = {263}, number = {}, pages = {127113}, doi = {10.1016/j.micres.2022.127113}, pmid = {35841835}, issn = {1618-0623}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Dysbiosis ; Humans ; *Microbiota ; Virulence ; }, abstract = {Clostridioides difficile infection (CDI), which mostly occurs in hospitalized patients, is the most common and costly health care-associated disease. However, the biology of C. difficile remains incompletely understood. Current therapeutics are still challenged by the frequent recurrence of CDI. Advances in metabolomics facilitate our understanding of the etiology of CDI, which is not merely an alteration in the structure of the gut microbial community but also a dysbiosis metabolic setting promoting the germination, expansion and virulence of C. difficile. Therefore, we summarized the gut microbial and metabolic profiles for CDI under different conditions, such as those of postantibiotic treatment and postfecal microbiota transplantation. The current understanding of the role of host and gut microbial-derived metabolites as well as other nutrients in preventing or alleviating the disease symptoms of CDI will also be provided in this review. We hope that a specific nutrient-centric dietary strategy or the administration of certain nutrients to the colon could serve as an alternate line of investigation for the prophylaxis and mitigation of CDI in the future. Nevertheless, rigorously designed basic studies and randomized controlled trials need to be conducted to assess the functional mechanisms and effects of such therapeutics.}, }
@article {pmid35840468, year = {2022}, author = {Pavanello, A and Martins, IP and Tófolo, LP and Previate, C and Matiusso, CCI and Francisco, FA and Prates, KV and Alves, VS and de Almeida, DL and Ribeiro, TA and Malta, A and Mathias, PCF}, title = {Fecal Microbiota Transplantation During Lactation Programs the Metabolism of Adult Wistar Rats in a Sex-specific Way.}, journal = {Archives of medical research}, volume = {53}, number = {5}, pages = {492-500}, doi = {10.1016/j.arcmed.2022.06.007}, pmid = {35840468}, issn = {1873-5487}, mesh = {Adipose Tissue/metabolism ; Animals ; Animals, Newborn ; Body Weight ; *Fecal Microbiota Transplantation ; Female ; *Lactation ; Male ; Obesity/metabolism/therapy ; Rats ; Rats, Wistar ; }, abstract = {BACKGROUND: The intestinal microbiota is involved in many physiological processes. However, the effects of microbiota in metabolic programming still unknow. We evaluated whether the transplantation of fecal microbiota during early life can program health or disease during adulthood in a model of lean and obese male and female Wistar rats.<br><br>METHODS: Parental obesity were induced using a small litter (SL, 3 pups/dam) model. At 90 d old, normal litter (NL, 9 pups/dam) and SL males and females (parents) from different litters were mated: NL male vs. NL female; SL male vs. SL female. After birth, male and female offspring rats were also standardized in normal litters or small litters . From the 10[th] until 25[th] d of life, the NL and SL male and female offspring received via gavage of a solution containing the diluted feces of the opposite dam (fecal microbiota, M) or saline solution (S). At 90 d of age, biometric and biochemical parameters were assessed.<br><br>RESULTS: NLM male rats transplanted with obese microbiota showed increased body weight, and fat pad deposition, hyperinsulinemia, glucose intolerance and dyslipidemia. SLM male rats transplanted with lean microbiota had decreased retroperitoneal and mesenteric fat, triglycerides and VLDL levels and improvement of glucose tolerance. Despite SLM female rats showed higher visceral fat, microbiota transplantation in female rats caused no changes in these parameters compared with control groups.<br><br>CONCLUSION: Fecal microbiota transplantation during lactation induces long-term effects on the metabolism of male Wistar rats. However, female rats were resistant to metabolic alterations caused by the treatment.}, }
@article {pmid35840401, year = {2022}, author = {Chen, Q and Xie, Q and Jiang, C and Evivie, SE and Cao, T and Wang, Z and Zhao, L and Liang, S and Li, B and Huo, G}, title = {Infant formula supplemented with 1,3-olein-2-palmitin regulated the immunity, gut microbiota, and metabolites of mice colonized by feces from healthy infants.}, journal = {Journal of dairy science}, volume = {105}, number = {8}, pages = {6405-6421}, doi = {10.3168/jds.2021-21736}, pmid = {35840401}, issn = {1525-3198}, mesh = {Animals ; Fatty Acids, Volatile/analysis ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Humans ; *Infant Formula/chemistry ; Mice ; Milk, Human/chemistry ; RNA, Ribosomal, 16S/analysis ; }, abstract = {Infant formula is currently an important food to cope with insufficient breastfeeding. Although 1,3-olein-2-palmitin (OPO) has been used in infant formula, its effects on the immune system, gut microbiota, and metabolites for infants remain unclear. This study constructed a mouse model of colonizing healthy infant feces using antibiotic treatment and fecal microbial transplantation. Thus, the gap between the infant formula supplemented with OPO and human milk in mouse serum biochemistry, immune system, intestinal microbiota, short-chain fatty acid production, and metabolites was evaluated. Our results showed that regarding IL-9, IL-10 levels, fecal secretory IgA, and endotoxin, formula supplemented with OPO and human milk types had comparable levels. Additionally, OPO slightly increased the content of short-chain fatty acids. The 16S rRNA gene sequence analysis and metabonomics analysis demonstrated that feeding different foods affects the gut microbiota of mice; in particular, supplementing formula feeding with OPO enriched the abundance of bifidobacteria. Furthermore, feeding different foods leads to unique intestinal content of metabolites, and the gut microbiota regulates the metabolites' differences. Our results reveal a brand new perspective of OPO regarding gut microbiota and metabolites.}, }
@article {pmid36286640, year = {2021}, author = {Iakupova, AA and Abdulkhakov, SR and Safin, AG and Alieva, IM and Oslopova, JV and Abdulkhakov, RA}, title = {[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)].}, journal = {Terapevticheskii arkhiv}, volume = {93}, number = {2}, pages = {215-221}, doi = {10.26442/00403660.2021.02.200615}, pmid = {36286640}, issn = {0040-3660}, abstract = {Fecal microbiota transplantation is a treatment method based on the introduction of donated fecal material to the recipient in order to restore the damaged composition of the intestinal microbiota. This review summarizes existing data on indications for fecal microbiota transplantation, recommendations for donor selection, processing and storage of donor biomaterial.}, }
@article {pmid36777748, year = {2020}, author = {Sood, A and Singh, A and Midha, V and Mahajan, R and Kao, D and Rubin, DT and Bernstein, CN}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis: An Evolving Therapy.}, journal = {Crohn's &amp; colitis 360}, volume = {2}, number = {4}, pages = {otaa067}, pmid = {36777748}, issn = {2631-827X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is currently an approved treatment for recurrent and refractory Clostridioides difficile infection. However, its use in ulcerative colitis is at an early stage and significant gaps remain in our understanding of the mechanisms and logistics of its practical application.<br><br>METHODS AND RESULTS: This article aims to look into specific issues which remain unsettled for use of FMT in ulcerative colitis including donor and recipient selection, route of administration, and duration of therapy. We also discuss optimal ways to assess response to FMT and the current state of FMT regulations. In addition, we postulate the impact of diet on the microbiome profile of the donor and recipient. We also suggest a change in the nomenclature from FMT to fecal microbiome transfer.<br><br>CONCLUSION: FMT is an evolving therapy. There are several considerations for its use in UC but its use and role should be directed by further clinical trials.}, }
@article {pmid36777294, year = {2020}, author = {Kayal, M and Lambin, T and Pinotti, R and Dubinsky, MC and Grinspan, A}, title = {A Systematic Review of Fecal Microbiota Transplant for the Management of Pouchitis.}, journal = {Crohn's &amp; colitis 360}, volume = {2}, number = {2}, pages = {otaa034}, pmid = {36777294}, issn = {2631-827X}, abstract = {BACKGROUND: Manipulation of the pouch microbiota via fecal microbiota transplant (FMT) has been theorized to be a promising therapeutic approach for pouchitis. The goal of this systematic review was to summarize the available, high-quality data on the efficacy and safety of FMT for acute and chronic pouchitis.<br><br>METHODS: A systematic electronic literature search was conducted on Embase, MEDLINE, Scopus, and Cochrane CENTRAL. Randomized controlled trials and observational studies that assessed the efficacy and safety of FMT for the treatment of acute and/or chronic pouchitis in patients with ulcerative colitis who underwent total proctocolectomy with ileal pouch-anal anastomosis were included.<br><br>RESULTS: Four studies involving the use of FMT for chronic pouchitis were considered eligible for data extraction. No study involving the use of FMT for the management of acute pouchitis was identified. In 1 study, 3/5 (75%) patients achieved sustained clinical remission at 3 months. In the remaining 3 studies, 2/8, 1/11, and 1/5 patients achieved clinical response defined as a decrease in pouchitis disease activity index at least 3. Stool donor engraftment as determined by 16s rRNA gene sequencing occurred only in those patients with clinical response.<br><br>CONCLUSIONS: The 4 studies that met inclusion criteria for this systematic review indicate FMT is safe in chronic pouchitis, however largely not efficacious. These data are limited by study heterogeneity. Additional studies are required to guide the use of FMT in patients with acute and chronic pouchitis.}, }
@article {pmid36777298, year = {2020}, author = {Raffals, LE}, title = {Self-administered Fecal Microbial Transplants-What Could Possibly Go Wrong?.}, journal = {Crohn's &amp; colitis 360}, volume = {2}, number = {2}, pages = {otaa025}, pmid = {36777298}, issn = {2631-827X}, }
@article {pmid36339288, year = {2019}, author = {Hota, SS and McNamara, I and Jin, R and Kissoon, M and Singh, S and Poutanen, SM}, title = {Challenges establishing a multi-purpose fecal microbiota transplantation stool donor program in Toronto, Canada.}, journal = {Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada}, volume = {4}, number = {4}, pages = {218-226}, pmid = {36339288}, issn = {2371-0888}, abstract = {BACKGROUND: The success of fecal microbiota transplantation (FMT) programs depends on maintaining suitable stool donors. We describe challenges recruiting and retaining universal donors in the first 2 years of an FMT clinical and research program in Toronto and identify opportunities for improvement.<br><br>METHODS: A four-stage screening process is used to identify suitable FMT donors in the Microbiota Therapeutics Outcomes Program. Donor screening follows Health Canada recommendations and excludes persons with history or risk for diseases associated with dysbiosis. Donors are rescreened microbiologically approximately every 1-3 months and answer ongoing health, exposure, and dietary questionnaires.<br><br>RESULTS: In the first 2 years of our program, 5 of 322 (1.6%) prospective stool donors passed initial screening, and only 2 (0.6%) were retained. Most prospective donors were excluded on telephone screening, at which point high BMI, medication use, and family history of relevant illness were common exclusions. No candidate was excluded because of a concerning physical examination. Microbiologic reasons for donor exclusion included carriage of Blastocystis hominis (n = 2), Helicobacter pylori (n = 2), extended spectrum beta-lactamase producing organisms (n = 1), Shiga-toxin producing Escherichia coli (n = 1), and sapovirus (n = 1). Universal donors were lost temporarily because of travel, antibiotic exposures, and transient carriage of antibiotic-resistant organisms.<br><br>CONCLUSIONS: Recruiting and retaining suitable donors for FMT is challenging because of rigorous exclusions and labour-intensive screening processes. We present considerations for efficiency in donor screening, including targeting recruitment populations, expanded website self-screening, eliminating physical examinations, and streamlining post-travel risk assessment.}, }
@article {pmid35837289, year = {2022}, author = {Xue, H and Ma, J and Wang, Y and Lu, M and Wang, F and Tang, X}, title = {Shen-Ling-Bai-Zhu-San (SL) and SL Derived-Polysaccharide (PL) Ameliorate the Severity of Diarrhea-Induced by High Lactose via Modification of Colonic Fermentation.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {883355}, pmid = {35837289}, issn = {1663-9812}, abstract = {In our previous study, we demonstrated that Shen-ling-bai-zhu-san (SL), a classical Chinese herbal formula, could alleviate lactose-induced diarrhea. However, little is known about the mechanism underlying SL action or the efficacy of the polysaccharide (PL) derived from SL. In this study, we investigated the effect of SL and PL on improving the dysregulated luminal and mucosal microbiota in rats with high lactose diet using 16S rRNA analysis. The concentrations of lactose, lactic acid in cecum and short-chain fatty acids (SCFAs) in cecum and portal vein were measured, meanwhile the expression of ion transporters were ascertained. Our data suggest that the SL, PL and cecal microbiota transplantation (CMT) significantly decreased fecal water content and water intake. In the luminal microbiota there was a significant increase in Akkermansia, Bifidobacterium and Blautia and a lower abundance of Lactobacillus, Escherichia-Shigella, and Dubosiella, while the mucosal microbiota showed a significant increase in Bifidobacterium, Akkermansia, Albaculum, Bilophila, and Coriobacteriaceae_UCG-002 and a lower abundance of Enterococcus, Helicobacter, Dubosiella, and Collinsella. Furthermore, the treatments enhanced lactose fermentation and SCFA production, which may be related to the modulation of the luminal microbial community. A lower ratio of phosphorylation Na/H exchanger3/Na/H exchanger3 (pNHE3/NHE3) and a higher sodium monocarboxylate1 (sMCT1) expression were found in the treatment group than in the model group, which may be related to the changes in the mucosal microbial community. Also, the treatments may restore the impacted metabolic pathways of gut microbiota. These results provide an important foundation for mechanism of SL action and developing PL-based treatment for lactose-induced diarrhea.}, }
@article {pmid35836813, year = {2022}, author = {Cong, J and Wu, D and Dai, H and Ma, Y and Liao, C and Li, L and Ye, L and Huang, Z}, title = {Interleukin-37 exacerbates experimental colitis in an intestinal microbiome-dependent fashion.}, journal = {Theranostics}, volume = {12}, number = {11}, pages = {5204-5219}, pmid = {35836813}, issn = {1838-7640}, mesh = {Animals ; Bacteria ; *Colitis/pathology ; Colon/metabolism ; Cytokines/metabolism ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Dysbiosis/metabolism ; *Gastrointestinal Microbiome ; Humans ; Inflammation/metabolism ; *Inflammatory Bowel Diseases/metabolism ; Interleukins/metabolism ; Mice ; Mice, Inbred C57BL ; }, abstract = {Background: Inflammatory bowel disease (IBD) involves complicated crosstalk between host immunity and the gut microbiome, whereas the mechanics of how they govern intestinal inflammation remain poorly understood. In this study, we investigated the contribution of environmental factors to shaping gut microbiota composition in colitis mice that were transgenic for human IL-37, a natural anti-inflammatory cytokine possessing pathogenic and protective functions related to microbiota alterations. Methods: Mice transgenic expressing human IL-37 (IL-37tg) were housed under conventional and specific pathogen-free (SPF) conditions to develop a mouse model of dextran sulfate sodium (DSS)-induced colitis. 16S ribosomal RNA sequencing was used for analyzing fecal microbial communities. The efficacy of microbiota in the development of colitis in IL-37tg mice was investigated after antibiotic treatment and fecal microbiota transplantation (FMT). The mechanism by which IL-37 worsened colitis was studied by evaluating intestinal epithelial barrier function, immune cell infiltration, the expression of diverse cytokines and chemokines, as well as activated signaling pathways. Results: We found that IL-37 overexpression aggravated DSS-induced colitis in conventional mice but protected against colitis in SPF mice. These conflicting results from IL-37tg colitis mice are ascribed to a dysbiosis of the gut microbiota in which detrimental bacteria increased in IL-37tg conventional mice. We further identified that the outcome of IL-37-caused colon inflammation is strongly related to intestinal epithelial barrier impairment caused by pathogenic bacteria, neutrophils, and NK cells recruitment in colon lamina propria and mesenteric lymph node to enhance inflammatory responses in IL-37tg conventional mice. Conclusions: The immunoregulatory properties of IL-37 are detrimental in the face of dysbiosis of the intestinal microbiota, which contributes to exacerbated IBD occurrences that are uncontrollable by the immune system, suggesting that depleting gut pathogenic bacteria or maintaining intestinal microbial and immune homeostasis could be a promising therapeutic strategy for IBD.}, }
@article {pmid35836252, year = {2022}, author = {Zhang, X and Akhtar, M and Chen, Y and Ma, Z and Liang, Y and Shi, D and Cheng, R and Cui, L and Hu, Y and Nafady, AA and Ansari, AR and Abdel-Kafy, EM and Liu, H}, title = {Chicken jejunal microbiota improves growth performance by mitigating intestinal inflammation.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {107}, pmid = {35836252}, issn = {2049-2618}, mesh = {Animals ; Body Weight ; *Chickens ; Female ; Inflammation ; Jejunum ; Male ; *Microbiota ; RNA, Ribosomal, 16S/genetics/metabolism ; }, abstract = {BACKGROUND: Intestinal inflammation is prevalent in chicken, which results in decreased growth performance and considerable economic losses. Accumulated findings established the close relationship between gut microbiota and chicken growth performance. However, whether gut microbiota impacts chicken growth performance by lessening intestinal inflammation remains elusive.<br><br>RESULTS: Seven-weeks-old male and female chickens with the highest or lowest body weights were significantly different in breast and leg muscle indices and average cross-sectional area of muscle cells. 16S rRNA gene sequencing indicated Gram-positive bacteria, such as Lactobacilli, were the predominant species in high body weight chickens. Conversely, Gram-negative bacteria, such as Comamonas, Acinetobacter, Brucella, Escherichia-Shigella, Thermus, Undibacterium, and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium were significantly abundant in low body weight chickens. Serum lipopolysaccharide (LPS) level was significantly higher in low body weight chickens (101.58 &#xb1; 5.78 ng/mL) compared with high body weight chickens (85.12 &#xb1; 4.79 ng/mL). The expression of TLR4, NF-&#x3ba;B, MyD88, and related inflammatory cytokines in the jejunum was significantly upregulated in low body weight chickens, which led to the damage of gut barrier integrity. Furthermore, transferring fecal microbiota from adult chickens with high body weight into 1-day-old chicks reshaped the jejunal microbiota, mitigated inflammatory response, and improved chicken growth performance.<br><br>CONCLUSIONS: Our findings suggested that jejunal microbiota could affect chicken growth performance by mitigating intestinal inflammation. Video Abstract.}, }
@article {pmid35836115, year = {2022}, author = {Hamazaki, M and Sawada, T and Yamamura, T and Maeda, K and Mizutani, Y and Ishikawa, E and Furune, S and Yamamoto, K and Ishikawa, T and Kakushima, N and Furukawa, K and Ohno, E and Honda, T and Kawashima, H and Ishigami, M and Nakamura, M and Fujishiro, M}, title = {Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan.}, journal = {BMC gastroenterology}, volume = {22}, number = {1}, pages = {342}, pmid = {35836115}, issn = {1471-230X}, support = {16K09406//the japan society for the promotion of science/ ; }, mesh = {Fecal Microbiota Transplantation/adverse effects ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/complications ; Japan ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a potential treatment for irritable bowel syndrome (IBS), but its efficacy in Japanese IBS patients is unknown. This study aimed to evaluate the efficacy, side effects, and microbiome changes following FMT in Japanese IBS patients.<br><br>METHODS: Seventeen Japanese patients with refractory IBS received FMT (4 donors) under colonoscopy. Responders were defined by an improvement in the IBS severity index (IBS-SI) of 50 points or more after 12&#xa0;weeks. We evaluated the IBS-SI and Bristol Stool Form Scale (BSFS) and compared the diversity and microbiome before and 12&#xa0;weeks after FMT. For the microbiome, we analyzed the V3-V4 region of the 16S rRNA gene.<br><br>RESULTS: IBS-SI decreased an average of 115.58 points after 12&#xa0;weeks, and 10 patients (58.8%) were considered responders. Eight patients with diarrhea (66.7%) and three patients with constipation (60.0%) showed improvement in the BSFS. Two patients complained of mild abdominal pain, but there were no cases with severe side-effects. &#x3b1;-diversity was increased only in the responder group (p&#x2009;=&#x2009;0.017). Patients who closely paralleled the donor microbiome had a higher rate of IBS-SI improvement. The relative abundance of Neisseria and Akkermansia increased and Desulfovibrio and Delftia were decreased in the responder group after FMT.<br><br>CONCLUSIONS: Following FMT, about 60% of Japanese patients with IBS showed improvement in both the IBS-SI and BSFS, without severe side effects. Increased &#x3b1;-diversity and similarity to the donor microbiome after FMT may be associated with better treatment effects.<br><br>TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trial Registration (UMIN000026363). Registered 31 May 2017, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000026363 . The study was registered prospectively.}, }
@article {pmid35835996, year = {2022}, author = {Merli, P and Massa, M and Russo, A and Rea, F and Del Chierico, F and Galaverna, F and Del Bufalo, F and Pane, S and Algeri, M and Romeo, EF and Masucci, L and De Angelis, P and Putignani, L and Locatelli, F}, title = {Fecal microbiota transplantation for the treatment of steroid-refractory, intestinal, graft-versus-host disease in a pediatric patient.}, journal = {Bone marrow transplantation}, volume = {57}, number = {10}, pages = {1600-1603}, pmid = {35835996}, issn = {1476-5365}, mesh = {Child ; Fecal Microbiota Transplantation ; *Graft vs Host Disease/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Steroids ; }, }
@article {pmid35832621, year = {2022}, author = {Balaji, A and Sapoval, N and Seto, C and Leo Elworth, RA and Fu, Y and Nute, MG and Savidge, T and Segarra, S and Treangen, TJ}, title = {KOMB: K-core based de novo characterization of copy number variation in microbiomes.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {3208-3222}, pmid = {35832621}, issn = {2001-0370}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; }, abstract = {Characterizing metagenomes via kmer-based, database-dependent taxonomic classification has yielded key insights into underlying microbiome dynamics. However, novel approaches are needed to track community dynamics and genomic flux within metagenomes, particularly in response to perturbations. We describe KOMB, a novel method for tracking genome level dynamics within microbiomes. KOMB utilizes K-core decomposition to identify Structural variations (SVs), specifically, population-level Copy Number Variation (CNV) within microbiomes. K-core decomposition partitions the graph into shells containing nodes of induced degree at least K, yielding reduced computational complexity compared to prior approaches. Through validation on a synthetic community, we show that KOMB recovers and profiles repetitive genomic regions in the sample. KOMB is shown to identify functionally-important regions in Human Microbiome Project datasets, and was used to analyze longitudinal data and identify keystone taxa in Fecal Microbiota Transplantation (FMT) samples. In summary, KOMB represents a novel graph-based, taxonomy-oblivious, and reference-free approach for tracking CNV within microbiomes. KOMB is open source and available for download at https://gitlab.com/treangenlab/komb.}, }
@article {pmid35832379, year = {2022}, author = {Li, Y and Zhang, T and Sun, J and Liu, N}, title = {Fecal Microbiota Transplantation and Health Outcomes: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {899845}, pmid = {35832379}, issn = {2235-2988}, mesh = {Constipation ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; *Irritable Bowel Syndrome ; Meta-Analysis as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Meta-analysis of randomized clinical trials (RCT) demonstrated several health benefits of fecal microbiota transplantation (FMT). However, there has been little comprehensive assessment of the strength and quality of evidence. We conducted an umbrella review to summarize the evidence of the association between FMT and health outcomes.<br><br>METHODS: PubMed, Embase, and Cochrane library databases were searched from inception to August 6, 2021. The random-effects model was applied to recalculate the effect estimates. We used AMSTAR 2 and GRADE to assess the methodological quality and to grade the evidence.<br><br>RESULTS: A total of 7 meta-analyses comprising 26 RCTs (median [IQR] primary study, 6 [2-7]; median [IQR] sample size, 267 [147-431] participants) were included in the current umbrella review describing 45 unique associations. There were 22 statistically significant associations (49%) demonstrating beneficial outcomes of FMT for antibiotic resistance burden, functional constipation, inflammatory bowel disease, and C. difficile infection. FMT does not appear to be associated with positive outcomes in irritable bowel syndrome and metabolic syndrome. Eight significant associations (36%) were supported by moderate-quality evidence, nine associations (41%) were supported by low-quality evidence, and the remaining associations found to be significant were supported by very low-quality evidence.<br><br>CONCLUSION: Although we found that FMT was positively associated with several outcomes, caution should be exercised in choosing this approach, given the insufficient number of primary studies, low methodological quality, and low quality of evidence. Further high-quality randomized controlled trials with long-term follow-up are needed to improve the strength and credibility of the evidence base.}, }
@article {pmid35831743, year = {2022}, author = {Konturek, PC}, title = {[Gut microbiota and chronic inflammatory bowel disease].}, journal = {MMW Fortschritte der Medizin}, volume = {164}, number = {Suppl 7}, pages = {12-15}, doi = {10.1007/s15006-022-1230-3}, pmid = {35831743}, issn = {1613-3560}, mesh = {Diet ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy ; }, abstract = {Intestinal dysbiosis remains the focus of research into the pathogenesis of chronic inflammatory bowel disease (IBD). The potential role of gut microbiota in the development of IBD includes interaction with the host genome and immune system, as well as various environmental factors, diet, drugs, industrialization, etc. Other organs are negatively affected by intestinal dysbiosis via gut-brain axis. The composition of microbiota and its metabolic activity has a significant impact on the effectiveness of anti-inflammatory therapies. Microbiome-based treatment for IBD includes the use of diet, antibiotics, pre-, pro- and synbiotics, and faecal transplantation (FMT). The development of effective therapies for IBD patients will only be possible once the interactions between the microbiota and its metabolites and the host immune system are better understood.}, }
@article {pmid35821195, year = {2022}, author = {Lu, G and Wen, Q and Cui, B and Li, Q and Zhang, F}, title = {Washed microbiota transplantation stopped the deterioration of amyotrophic lateral sclerosis: The first case report and narrative review.}, journal = {Journal of biomedical research}, volume = {37}, number = {1}, pages = {69-76}, pmid = {35821195}, issn = {1674-8301}, abstract = {Amyotrophic lateral sclerosis (ALS) is known as a progressive paralysis disorder characterized by degeneration of upper and lower motor neurons, and has an average survival time of three to five years. Growing evidence has suggested a bidirectional link between gut microbiota and neurodegeneration. Here we aimed to report one female case with ALS, who benefited from washed microbiota transplantation (WMT), an improved fecal microbiota transplantation (FMT), through a transendoscopic enteral tube during a 12-month follow-up. Notedly, the accidental scalp trauma the patient suffered later was treated with prescribed antibiotics that caused ALS deterioration. The subsequent rescue WMTs successfully stopped the progression of the disease with a quick improvement. The plateaus and reversals occurred during the whole course of WMT. The stool and blood samples from the first WMT to the last were collected for dynamic microbial and metabolomic analysis. We observed the microbial and metabolomic changing trend consistent with the disease status. This case report for the first time shows the direct clinical evidence on using WMT for treating ALS, indicating that WMT may be the novel treatment strategy for controlling this so-called incurable disease.}, }
@article {pmid35816618, year = {2022}, author = {Kesh, K and Mendez, R and Mateo-Victoriano, B and Garrido, VT and Durden, B and Gupta, VK and Oliveras Reyes, A and Merchant, N and Datta, J and Banerjee, S and Banerjee, S}, title = {Obesity enriches for tumor protective microbial metabolites and treatment refractory cells to confer therapy resistance in PDAC.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2096328}, pmid = {35816618}, issn = {1949-0984}, support = {P30 CA240139/CA/NCI NIH HHS/United States ; R01 CA124723/CA/NCI NIH HHS/United States ; R01 CA184274/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome/physiology ; Mice ; Mice, Inbred C57BL ; Nucleoside Q ; Obesity/metabolism ; *Pancreatic Neoplasms/complications ; }, abstract = {Obesity causes chronic inflammation and changes in gut microbiome. However, how this contributes to poor survival and therapy resistance in patients with pancreatic cancer remain undetermined. Our current study shows that high fat diet-fed obese pancreatic tumor bearing mice do not respond to standard of care therapy with gemcitabine and paclitaxel when compared to corresponding control diet-fed mice. C57BL6 mice were put on control and high fat diet for 1 month following with pancreatic tumors were implanted in both groups. Microbiome of lean (control) and obese (high fat diet fed) mice was analyzed. Fecal matter transplant from control mice to obese mice sensitized tumors to chemotherapy and demonstrated extensive cell death. Analysis of gut microbiome showed an enrichment of queuosine (Q) producing bacteria in obese mice and an enrichment of S-adenosyl methionine (SAM) producing bacteria in control diet-fed mice. Further, supplementation of obese animals with SAM sensitized pancreatic tumors to chemotherapy. Treatment of pancreatic cancer cells with Q increased PRDX1 involved in oxidative stress protection. In parallel, tumors in obese mice showed increase in CD133[+] treatment refractory tumor populations compared to control animals. These observations indicated that microbial metabolite Q accumulation in high fat diet-fed mice protected tumors from chemotherapy induced oxidative stress by upregulating PRDX1. This protection could be reversed by treatment with SAM. We conclude that relative concentration of SAM and queuosine in fecal samples of pancreatic cancer patients can be developed as a potential biomarker and therapeutic target in chemotherapy refractory pancreatic cancer.}, }
@article {pmid35814686, year = {2022}, author = {Wu, J and Wang, L and Wei, Y and Yang, J and Chen, Z and Hao, P and Lv, Y and Wang, M and Liao, F and Chang, L and Liu, Y and Chen, Z}, title = {Editorial: Multi-Omics Study on Gut Microbiota Related to Faecal Microbiota Transplantation.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {944879}, doi = {10.3389/fmicb.2022.944879}, pmid = {35814686}, issn = {1664-302X}, }
@article {pmid35814647, year = {2022}, author = {Huang, WQ and Huang, HL and Peng, W and Liu, YD and Zhou, YL and Xu, HM and Zhang, LJ and Zhao, C and Nie, YQ}, title = {Altered Pattern of Immunoglobulin A-Targeted Microbiota in Inflammatory Bowel Disease After Fecal Transplantation.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {873018}, pmid = {35814647}, issn = {1664-302X}, abstract = {Adaptive immune response to the gut microbiota is one of the main drivers of inflammatory bowel disease (IBD). Under inflammatory conditions, immunoglobulin (Ig)-targeted bacteria are altered. However, changes in Ig-targeted bacteria in Asian patients with IBD with ulcerative colitis (UC) remain unclear. Furthermore, changes in IgA-targeted bacteria in patients with UC treated with fecal microbiota transplantation (FMT) are unclear. Here, we analyzed fecal samples of patients with IBD and patients with UC before and after FMT by flow cytometry. We found that the percentage of IgA/G-coated bacteria can be used to assess the severity of IBD. Besides oral pharyngeal bacteria such as Streptococcus, we hypothesized that Megamonas, Acinetobacter, and, especially, Staphylococcus might play an important role in IBD pathogenesis. Moreover, we evaluated the influence of FMT on IgA-coated bacteria in patients with UC. We found that IgA-bacterial interactions were re-established in human FMT recipients and resembled those in the healthy fecal donors. Additionally, the IgA targeting was not influenced by delivery methods: gastroscopy spraying and colonic transendoscopic enteral tubing (TET). Then, we established an acute dextran sulfate sodium (DSS)-induced mouse model to explore whether FMT intervention would impact IgA/G memory B cell in the intestine. We found that after FMT, both IgA/G memory B cell and the percentage of IgA/G-targeted bacteria were restored to normal levels in DSS mice.}, }
@article {pmid35814520, year = {2022}, author = {Rajpurohit, S and Musunuri, B and Shailesh,  and Basthi Mohan, P and Shetty, S}, title = {Novel Drugs for the Management of Hepatic Encephalopathy: Still a Long Journey to Travel.}, journal = {Journal of clinical and experimental hepatology}, volume = {12}, number = {4}, pages = {1200-1214}, pmid = {35814520}, issn = {0973-6883}, abstract = {Hepatic encephalopathy (HE) is one of the reversible complications of chronic liver disease, associated with a higher mortality rate. In current clinical practice, treatment with rifaximin and lactulose/lactitol is the first line of treatment in HE. With the advance in pathophysiology, a new class of ammonia lowering drugs has been revealed to overcome the hurdle and disease burden. The mechanism of the novel agents differs significantly and includes the alteration in intestinal microbiota, intestinal endothelial integrity, oxidative stress, inflammatory markers, and modulation of neurotoxins. Most of the trials have reported promising results in the treatment and prevention of HE with fecal microbiota transplantation, albumin, probiotics, flumazenil, polyethylene glycol, AST-120, glycerol phenylbutyrate, nitazoxanide, branched-chain amino acid, naloxone, and acetyl-l-carnitine. However, their clinical use is limited due to the presence of major drawbacks in their study design, sample size, safety profile, bias, and heterogenicity. This study will discuss the novel therapeutic targets for HE in liver cirrhosis patients with supporting clinical trial data.}, }
@article {pmid35814513, year = {2022}, author = {Philips, CA and Ahamed, R and Rajesh, S and Abduljaleel, JKP and Augustine, P}, title = {Long-term Outcomes of Stool Transplant in Alcohol-associated Hepatitis-Analysis of Clinical Outcomes, Relapse, Gut Microbiota and Comparisons with Standard Care.}, journal = {Journal of clinical and experimental hepatology}, volume = {12}, number = {4}, pages = {1124-1132}, pmid = {35814513}, issn = {0973-6883}, abstract = {BACKGROUND: Healthy donor fecal microbiota transplantation (FMT) was preliminarily shown to have clinical benefits in hepatic encephalopathy (HE), severe alcohol-associated hepatitis (SAH), and alcohol use disorder. However, the long-term outcomes of FMT and the gut microbiota (GM) changes in patients with SAH are unknown.<br><br>METHODS: Patients with SAH who underwent FMT (N&#xa0;=&#xa0;35) or standard of care (SoC, N&#xa0;=&#xa0;26) from May 2017 to June 2018 were included, and their stored stool samples were analyzed prospectively. Clinical outcomes, including infections, hospitalizations, critical illness, alcohol relapse, and survival, were evaluated. Metagenomic analysis was undertaken to identify the relative abundances (Ras) and significant taxa at baseline and post-therapy (up to three years) among survivors between the two groups.<br><br>RESULTS: At follow-up, the incidences of ascites, HE, infections, and major hospitalizations were significantly higher in the SoC than in the FMT group (P&#xa0;<&#xa0;0.05). Alcohol relapse was lower (28.6% versus 53.8%), and the time to relapse was higher in the FMT than in the SoC group (P&#xa0;=&#xa0;0.04). Three-year survival was higher in the FMT than in the SoC group (65.7% versus 38.5%, P&#xa0;=&#xa0;0.052). Death due to sepsis was significantly higher in the SoC group (N&#xa0;=&#xa0;13/16, 81.2%; P&#xa0;=&#xa0;0.008). GM analysis showed a significant increase in the RA of Bifidobacterium and a reduction in the RA of Acinetobacter in the FMT group. Beyond one to two years, the RA of Porphyromonas was significantly higher and that of Bifidobacterium was lower in the SoC than in the FMT group.<br><br>CONCLUSIONS: In terms of treatment for patients with SAH, healthy donor FMT is associated with significantly lesser ascites, infections, encephalopathy, and alcohol relapse (with a trend toward higher survival rates) than SoC, associated with beneficial GM modulation. Larger controlled studies on FMT are an unmet need.}, }
@article {pmid35812394, year = {2022}, author = {Zhu, M and Liu, X and Ye, Y and Yan, X and Cheng, Y and Zhao, L and Chen, F and Ling, Z}, title = {Gut Microbiota: A Novel Therapeutic Target for Parkinson's Disease.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {937555}, pmid = {35812394}, issn = {1664-3224}, mesh = {Animals ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Neurodegenerative Diseases ; *Parkinson Disease/pathology ; }, abstract = {Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by motor dysfunction. Growing evidence has demonstrated that gut dysbiosis is involved in the occurrence, development and progression of PD. Numerous clinical trials have identified the characteristics of the changed gut microbiota profiles, and preclinical studies in PD animal models have indicated that gut dysbiosis can influence the progression and onset of PD via increasing intestinal permeability, aggravating neuroinflammation, aggregating abnormal levels of α-synuclein fibrils, increasing oxidative stress, and decreasing neurotransmitter production. The gut microbiota can be considered promising diagnostic and therapeutic targets for PD, which can be regulated by probiotics, psychobiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, diet modifications, and Chinese medicine. This review summarizes the recent studies in PD-associated gut microbiota profiles and functions, the potential roles, and mechanisms of gut microbiota in PD, and gut microbiota-targeted interventions for PD. Deciphering the underlying roles and mechanisms of the PD-associated gut microbiota will help interpret the pathogenesis of PD from new perspectives and elucidate novel therapeutic strategies for PD.}, }
@article {pmid35812374, year = {2022}, author = {Li, P and Gao, M and Song, B and Liu, Y and Yan, S and Lei, J and Zhao, Y and Li, G and Mahmood, T and Lv, Z and Hu, Y and Guo, Y}, title = {Fecal Microbiota Transplantation Reshapes the Physiological Function of the Intestine in Antibiotic-Treated Specific Pathogen-Free Birds.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {884615}, pmid = {35812374}, issn = {1664-3224}, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology ; Antioxidants ; Bacteria ; Birds ; *Fecal Microbiota Transplantation ; Intestines ; }, abstract = {The topic about the interactions between host and intestinal microbiota has already caught the attention of many scholars. However, there is still a lack of systematic reports on the relationship between the intestinal flora and intestinal physiology of birds. Thus, this study was designed to investigate it. Antibiotic-treated specific pathogen-free (SPF) bird were used to construct an intestinal bacteria-free bird (IBF) model, and then, the differences in intestinal absorption, barrier, immune, antioxidant and metabolic functions between IBF and bacteria-bearing birds were studied. To gain further insight, the whole intestinal flora of bacteria-bearing birds was transplanted into the intestines of IBF birds to study the remodeling effect of fecal microbiota transplantation (FMT) on the intestinal physiology of IBF birds. The results showed that compared with bacteria-bearing birds, IBF birds had a lighter body weight and weaker intestinal absorption, antioxidant, barrier, immune and metabolic functions. Interestingly, FMT contributed to reshaping the abovementioned physiological functions of the intestines of IBF birds. In conclusion, the intestinal flora plays an important role in regulating the physiological functions of the intestine.}, }
@article {pmid35811664, year = {2022}, author = {Wang, X and Zhao, J and Feng, Y and Feng, Z and Ye, Y and Liu, L and Kang, G and Cao, X}, title = {Evolutionary Insights Into Microbiota Transplantation in Inflammatory Bowel Disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {916543}, pmid = {35811664}, issn = {2235-2988}, mesh = {Chronic Disease ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases/therapy ; *Microbiota ; }, abstract = {The intestinal microbiome plays an essential role in human health and disease status. So far, microbiota transplantation is considered a potential therapeutic approach for treating some chronic diseases, including inflammatory bowel disease (IBD). The diversity of gut microbiota is critical for maintaining resilience, and therefore, transplantation with numerous genetically diverse gut microbiota with metabolic flexibility and functional redundancy can effectively improve gut health than a single probiotic strain supplement. Studies have shown that natural fecal microbiota transplantation or washing microbiota transplantation can alleviate colitis and improve intestinal dysbiosis in IBD patients. However, unexpected adverse reactions caused by the complex and unclear composition of the flora limit its wider application. The evolving strain isolation technology and modifiable pre-existing strains are driving the development of microbiota transplantation. This review summarized the updating clinical and preclinical data of IBD treatments from fecal microbiota transplantation to washing microbiota transplantation, and then to artificial consortium transplantation. In addition, the factors considered for strain combination were reviewed. Furthermore, four types of artificial consortium transplant products were collected to analyze their combination and possible compatibility principles. The perspective on individualized microbiota transplantation was also discussed ultimately.}, }
@article {pmid35811073, year = {2022}, author = {Das, S and Song, Z and Han, H and Ge, X and Desert, R and Athavale, D and Babu Komakula, SS and Magdaleno, F and Chen, W and Lantvit, D and Guzman, G and Nieto, N}, title = {Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {14}, number = {4}, pages = {813-839}, pmid = {35811073}, issn = {2352-345X}, support = {I01 BX005093/BX/BLRD VA/United States ; R01 AA025907/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; *Chemical and Drug Induced Liver Injury, Chronic/complications ; Ethanol/toxicity ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome/genetics/physiology ; Interleukin-33 ; *Intestines/metabolism ; *Liver Diseases, Alcoholic/genetics/metabolism/prevention &amp; control ; Mice ; Mice, Inbred C57BL ; *Osteopontin/genetics/metabolism ; Receptors, Aryl Hydrocarbon ; Tryptophan ; }, abstract = {BACKGROUND &amp; AIMS: The gut-liver axis plays a key role in the pathogenesis of alcohol-associated liver disease (ALD). We demonstrated that Opn[-/-] develop worse ALD than wild-type (WT) mice; however, the role of intestinal osteopontin (OPN) in ALD remains unknown. We hypothesized that overexpression of OPN in intestinal epithelial cells (IECs) could ameliorate ALD by preserving the gut microbiome and the intestinal barrier function.<br><br>METHODS: Opn[KI IEC], Opn[&#x394;IEC], and WT mice were fed control or ethanol Lieber-DeCarli diet for 6 weeks.<br><br>RESULTS: Opn[KI IEC] but not Opn[&#x394;IEC] mice showed improved intestinal barrier function and protection from ALD. There were less pathogenic and more beneficial bacteria in ethanol-fed Opn[KI IEC] than in WT mice. Fecal microbiome transplant (FMT) from Opn[KI IEC] to WT mice protected from ALD. FMT from ethanol-fed WT to Opn[KI IEC] mice failed to induce ALD. Antimicrobial peptides, Il33, pSTAT3, aryl hydrocarbon receptor (Ahr), and tight-junction protein expression were higher in IECs from jejunum of ethanol-fed Opn[KI IEC] than of WT mice. Ethanol-fed Opn[KI IEC] showed more tryptophan metabolites and short-chain fatty acids in portal serum than WT mice. FMT from Opn[KI IEC] to WT mice enhanced IECs Ahr and tight-junction protein expression. Oral administration of milk OPN replicated the protective effect of Opn[KI IEC] mice in ALD.<br><br>CONCLUSION: Overexpression of OPN in IECs or administration of milk OPN maintain the intestinal microbiome by intestinal antimicrobial peptides. The increase in tryptophan metabolites and short-chain fatty acids signaling through the Ahr in IECs, preserve the intestinal barrier function and protect from ALD.}, }
@article {pmid35809615, year = {2022}, author = {Camilleri, M and Dilmaghani, S}, title = {Treatment of Irritable Bowel Syndrome Using Fecal Microbiota Transplantation: A Step Forward?.}, journal = {Gastroenterology}, volume = {163}, number = {4}, pages = {815-817}, pmid = {35809615}, issn = {1528-0012}, support = {R01 DK115950/DK/NIDDK NIH HHS/United States ; }, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid35807816, year = {2022}, author = {Xu, B and Hao, K and Chen, X and Wu, E and Nie, D and Zhang, G and Si, H}, title = {Broussonetia papyrifera Polysaccharide Alleviated Acetaminophen-Induced Liver Injury by Regulating the Intestinal Flora.}, journal = {Nutrients}, volume = {14}, number = {13}, pages = {}, pmid = {35807816}, issn = {2072-6643}, support = {AB19245037//The Key Research and Development Plan of Guangxi, China/ ; 20202088//Key R &amp; D Projects in Nanning/ ; 31760746//Natural National Science Foundation of China/ ; }, mesh = {Acetaminophen/toxicity ; Animals ; *Broussonetia ; *Chemical and Drug Induced Liver Injury/metabolism/prevention &amp; control ; *Chemical and Drug Induced Liver Injury, Chronic ; *Gastrointestinal Microbiome ; Liver/metabolism ; Mice ; Oxidative Stress ; Polysaccharides/metabolism/pharmacology/therapeutic use ; }, abstract = {Liver injury caused by an overdose of acetaminophen (APAP) is a major public health problem. This study aimed to evaluate the effects of Broussonetia papyrifera polysaccharide (BPP) on liver injury and intestinal flora induced by APAP. The results showed that BPP could protect against APAP-induced liver injury, alleviate liver apoptosis, improve antioxidant capacity and enhance the liver's detoxification ability to APAP. At the same time, BPP improved the intestinal flora disorder caused by APAP. More importantly, we found that the hepatoprotective effect of BPP disappeared after the depletion of gut microbiota in mice. Further, we reconstructed the intestinal flora structure of mice through fecal microbiota transplantation and found that the symptoms of APAP-induced liver injury were effectively alleviated. Overall, BPP was a potential hepatoprotective drug that could protect against APAP-induced liver injury and might be mediated by intestinal flora.}, }
@article {pmid35806031, year = {2022}, author = {Rodríguez-Fernández, CA and Iglesias, MB and de Domingo, B and Conde-Pérez, K and Vallejo, JA and Rodríguez-Martínez, L and González-Barcia, M and Llorenç, V and Mondelo-Garcia, C and Poza, M and Fernández-Ferreiro, A}, title = {Microbiome in Immune-Mediated Uveitis.}, journal = {International journal of molecular sciences}, volume = {23}, number = {13}, pages = {}, pmid = {35806031}, issn = {1422-0067}, support = {IN607D 2021//Xunta de Galicia/ ; IN607A 2020/05//Xunta de Galicia/ ; PI20/00719//Instituto de Salud Carlos III/ ; PI20/00413//Instituto de Salud Carlos III/ ; }, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota/physiology ; Tumor Necrosis Factor Inhibitors ; *Uveitis/therapy ; }, abstract = {In the last decades, personalized medicine has been increasing its presence in different fields of medicine, including ophthalmology. A new factor that can help us direct medicine towards the challenge of personalized treatments is the microbiome. The gut microbiome plays an important role in controlling immune response, and dysbiosis has been associated with immune-mediated diseases such as non-infectious uveitis (NIU). In this review, we gather the published evidence, both in the pre-clinical and clinical studies, that support the possible role of intestinal dysbiosis in the pathogenesis of NIU, as well as the modulation of the gut microbiota as a new possible therapeutic target. We describe the different mechanisms that have been proposed to involve dysbiosis in the causality of NIU, as well as the potential pharmacological tools that could be used to modify the microbiome (dietary supplementation, antibiotics, fecal microbiota transplantation, immunomodulators, or biologic drugs) and, consequently, in the control of the NIU. Furthermore, there is increasing scientific evidence suggesting that the treatment with anti-TNF not only restores the composition of the gut microbiota but also that the study of the composition of the gut microbiome will help predict the response of each patient to anti-TNF treatment.}, }
@article {pmid35805965, year = {2022}, author = {Elhag, DA and Kumar, M and Saadaoui, M and Akobeng, AK and Al-Mudahka, F and Elawad, M and Al Khodor, S}, title = {Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response.}, journal = {International journal of molecular sciences}, volume = {23}, number = {13}, pages = {}, pmid = {35805965}, issn = {1422-0067}, support = {NPRP10-0125-170242//Qatar National Research Fund/ ; }, mesh = {Biomarkers ; Cytokines/therapeutic use ; Humans ; Immunologic Factors/therapeutic use ; Inflammation ; *Inflammatory Bowel Diseases/drug therapy ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time. Therefore, according to the recent Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations, continuous disease monitoring from symptomatic relief to endoscopic healing along with short- and long-term therapeutic responses are critical for providing IBD patients with a tailored therapy algorithm. Moreover, considering the high unmet need for novel therapeutic approaches for IBD patients, various new modulators of cytokine signaling events (for example, JAK/TYK inhibitors), inhibitors of cytokines (for example IL-12/IL-23, IL-22, IL-36, and IL-6 inhibitors), anti-adhesion and migration strategies (for example, β7 integrin, sphingosine 1-phosphate receptors, and stem cells), as well as microbial-based therapeutics to decolonize the bed buds (for example, fecal microbiota transplantation and bacterial inhibitors) are currently being evaluated in different phases of controlled clinical trials. This review aims to offer a comprehensive overview of available treatment options and emerging therapeutic approaches for IBD patients. Furthermore, predictive biomarkers for monitoring the therapeutic response to different IBD therapies are also discussed.}, }
@article {pmid35804021, year = {2022}, author = {Song, C and Duan, F and Ju, T and Qin, Y and Zeng, D and Shan, S and Shi, Y and Zhang, Y and Lu, W}, title = {Eleutheroside E supplementation prevents radiation-induced cognitive impairment and activates PKA signaling via gut microbiota.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {680}, pmid = {35804021}, issn = {2399-3642}, mesh = {Animals ; *Cognitive Dysfunction/etiology/metabolism/prevention &amp; control ; Dietary Supplements ; *Gastrointestinal Microbiome ; Glucosides ; *Lignans/pharmacology ; Mice ; }, abstract = {Radiation affects not only cognitive function but also gut microbiota. Eleutheroside E (EE), a principal active compound of Acanthopanax senticosus, has a certain protective effect on the nervous system. Here, we find a four-week EE supplementation to the [60]Co-γ ray irradiated mice improves the cognition and spatial memory impairments along with the protection of hippocampal neurons, remodels the gut microbiota, especially changes of Lactobacillus and Helicobacter, and altered the microbial metabolites including neurotransmitters (GABA, NE, ACH, 5-HT) as well as their precursors. Furthermore, the fecal transplantation of EE donors verifies that EE alleviated cognition and spatial memory impairments, and activates the PKA/CREB/BDNF signaling via gut microbiota. Our findings provide insight into the mechanism of EE effect on the gut-brain axis and underpin a proposed therapeutic value of EE in cognitive and memory impairments induced by radiation.}, }
@article {pmid35803979, year = {2022}, author = {Xie, W and Lorenz, M and Poosch, F and Palme, R and Zechner, D and Vollmar, B and Grambow, E and Strüder, D}, title = {3D-printed lightweight dorsal skin fold chambers from PEEK reduce chamber-related animal distress.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {11599}, pmid = {35803979}, issn = {2045-2322}, mesh = {Animals ; Benzophenones ; Body Weight ; *Corticosterone ; Ketones ; Mice ; Polyethylene Glycols ; Polymers ; Printing, Three-Dimensional ; *Titanium ; }, abstract = {The dorsal skinfold chamber is one of the most important in vivo models for repetitive longitudinal assessment of microcirculation and inflammation. This study aimed to refine this model by introducing a new lightweight chamber made from polyetheretherketone (PEEK). Body weight, burrowing activity, distress, faecal corticosterone metabolites and the tilting angle of the chambers were analysed in mice carrying either a standard titanium chamber or a PEEK chamber. Data was obtained before chamber preparation and over a postoperative period of three weeks. In the early postoperative phase, reduced body weight and increased faecal corticosterone metabolites were found in mice with titanium chambers. Chamber tilting and tilting-related complications were reduced in mice with PEEK chambers. The distress score was significantly increased in both groups after chamber preparation, but only returned to preoperative values in mice with PEEK chambers. In summary, we have shown that light chambers reduce animal distress and may extend the maximum dorsal skinfold chamber observation time. Chambers made of PEEK are particularly suitable for this purpose: They are autoclavable, sufficiently stable to withstand rodent bites, inexpensive, and widely available through 3D printing.}, }
@article {pmid35802940, year = {2022}, author = {Tian, Y and Zuo, L and Guan, B and Wu, H and He, Y and Xu, Z and Shen, M and Hu, J and Qian, J}, title = {Microbiota from patients with ulcerative colitis promote colorectal carcinogenesis in mice.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {102}, number = {}, pages = {111712}, doi = {10.1016/j.nut.2022.111712}, pmid = {35802940}, issn = {1873-1244}, mesh = {Animals ; Carcinogenesis ; *Colitis, Ulcerative/complications ; *Colonic Neoplasms ; Cytokines ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {OBJECTIVES: Long-term ulcerative colitis (UC) is associated with both dysbiosis in intestinal microbiota and predisposition to colorectal cancer. In this study, we investigated whether microbiota from patients with UC could increase colorectal carcinogenesis in mice, generated by azoxymethane through intraperitoneal injection.<br><br>METHODS: Mice were gavaged twice per week with intestinal microbiota from patients with UC or healthy individuals. Intestinal tissues were collected from mice and compared by histology, immunohistochemistry, expression microarray, quantitative polymerase chain reaction, Western blot, and flow cytometry analyses. Quantification of bacteria in feces was performed using 16 S ribosomal RNA gene selective quantitative polymerase chain reaction.<br><br>RESULTS: Compared with mice fed microbiota from healthy controls, increased tumorigenesis was observed in mice gavaged with microbiota from patients with UC, including a higher number of colon adenoma and a significantly higher proportion of grade dysplasia. Consistent with tumorigenesis, mice gavaged with microbiota from patients with UC showed an increased expression of Ki67 and proliferating cell nuclear antigen. In addition, an increased expression of cytokines and more abundant presence of T helper cells types 1 and 17 was observed in mice receiving microbiota from patients with UC. Moreover, a decrease in the abundance of short-chain fatty acids was detected in the feces, as well as an altered intestinal microbial composition in mice fed with microbiota from patients with UC.<br><br>CONCLUSIONS: Fecal microbiota from patients with UC exacerbate tumorigenesis in mice. The disturbance of intestinal microbiota and activation of T helper cells types 1 and 17 cytokines caused by gavaging microbiota from patients with UC both contributed to intestinal carcinogenesis.}, }
@article {pmid35800791, year = {2022}, author = {Tun, KM and Hong, AS and Batra, K and Naga, Y and Ohning, G}, title = {A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplantation in the Treatment of Hepatic Encephalopathy and Clostridioides difficile Infection in Patients With Cirrhosis.}, journal = {Cureus}, volume = {14}, number = {5}, pages = {e25537}, pmid = {35800791}, issn = {2168-8184}, abstract = {The microbiome of the human gut and liver coexists by influencing the health and disease state of each system. Fecal microbiota transplantation (FMT) has recently emerged as a potential treatment for conditions associated with cirrhosis, such as hepatic encephalopathy and recurrent/refractory Clostridioides difficile infection (rCDI). We have conducted a systematic review of the safety and efficacy of FMT in treating hepatic encephalopathy and rCDI. A literature search was performed using variations of the keywords "fecal microbiota transplant" and "cirrhosis" on PubMed/MEDLINE from inception to October 3, 2021. The resulting 116 articles were independently reviewed by two authors. Eight qualifying studies were included in the systematic review. A total of 127 cirrhotic patients received FMT. Hepatic encephalopathy was evaluated by cognitive tests, such as the Psychometric Hepatic Encephalopathy Score (PHES) and EncephalApp Stroop test. Not only was there an improvement in the cognitive performance in the FMT cohort, but the improvement was also maintained throughout long-term follow-up. In the treatment of rCDI, the FMT success rate is similar between cirrhotic patients and the general population, although more than one dose may be needed in the former. The rate of serious adverse events and adverse events in the cirrhotic cohort was slightly higher than that in the general population but was low overall. We found evidence that supports the therapeutic potential and safety profile of FMT to treat hepatic encephalopathy and rCDI in cirrhotic patients. Further research will be beneficial to better understand the role of FMT in cirrhosis.}, }
@article {pmid35799838, year = {2022}, author = {Ramírez, GA and Keshri, J and Vahrson, I and Garber, AI and Berrang, ME and Cox, NA and González-Cerón, F and Aggrey, SE and Oakley, BB}, title = {Cecal Microbial Hydrogen Cycling Potential Is Linked to Feed Efficiency Phenotypes in Chickens.}, journal = {Frontiers in veterinary science}, volume = {9}, number = {}, pages = {904698}, pmid = {35799838}, issn = {2297-1769}, abstract = {In chickens, early life exposure to environmental microbes has long-lasting impacts on gastrointestinal (GI) microbiome development and host health and growth, via mechanisms that remain uncharacterized. In this study, we demonstrated that administrating a fecal microbiome transplant (FMT) from adults to day-of-hatch chicks results in significantly higher body mass of birds and decreased residual feed intake (RFI), implying enhanced feed efficiency, at 6 weeks of age. To assess the potential mechanisms through which FMT affects adult bird phenotype, we combined 16 S rRNA gene amplification, metagenomic, and comparative genomic approaches to survey the composition and predicted activities of the resident microbiome of various GI tract segments. Early life FMT exposure had a long-lasting significant effect on the microbial community composition and function of the ceca but not on other GI segments. Within the ceca of 6-week-old FMT birds, hydrogenotrophic microbial lineages and genes were most differentially enriched. The results suggest that thermodynamic regulation in the cecum, in this case via hydrogenotrophic methanogenic and sulfur-cycling lineages, potentially serving as hydrogen sinks, may enhance fermentative efficiency and dietary energy harvest capacity. Our study provides a specific mechanism of action through which early-life microbiome transplants modulate market-relevant phenotypes in poultry and, thereby, may represent a significant advance toward microbiome-focused sustainable agriculture.}, }
@article {pmid35799219, year = {2022}, author = {Sinha, A and Li, Y and Mirzaei, MK and Shamash, M and Samadfam, R and King, IL and Maurice, CF}, title = {Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates the severity of DSS colitis.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {105}, pmid = {35799219}, issn = {2049-2618}, support = {170921//CIHR/Canada ; }, mesh = {Animals ; Bacteria/genetics ; *Bacteriophages/genetics ; *Colitis/therapy ; *Colitis, Ulcerative/microbiology/therapy ; *Gastrointestinal Microbiome ; Inflammation ; *Inflammatory Bowel Diseases/microbiology ; Mice ; }, abstract = {BACKGROUND: Inflammatory bowel diseases (IBDs) including Crohn's disease (CD) and ulcerative colitis (UC) are characterized by chronic and debilitating gut inflammation. Altered bacterial communities of the intestine are strongly associated with IBD initiation and progression. The gut virome, which is primarily composed of bacterial viruses (bacteriophages, phages), is thought to be an important factor regulating and shaping microbial communities in the gut. While alterations in the gut virome have been observed in IBD patients, the contribution of these viruses to alterations in the bacterial community and heightened inflammatory responses associated with IBD patients remains largely unknown.<br><br>RESULTS: Here, we performed in vivo microbial cross-infection experiments to follow the effects of fecal virus-like particles (VLPs) isolated from UC patients and healthy controls on bacterial diversity and severity of experimental colitis in human microbiota-associated (HMA) mice. Shotgun metagenomics confirmed that several phages were transferred to HMA mice, resulting in treatment-specific alterations in the gut virome. VLPs from healthy and UC patients also shifted gut bacterial diversity of these mice, an effect that was amplified during experimental colitis. VLPs isolated from UC patients specifically altered the relative abundance of several bacterial taxa previously implicated in IBD progression. Additionally, UC VLP administration heightened colitis severity in HMA mice, as indicated by shortened colon length and increased pro-inflammatory cytokine production. Importantly, this effect was dependent on intact VLPs.<br><br>CONCLUSIONS: Our findings build on recent literature indicating that phages are dynamic regulators of bacterial communities in the gut and implicate the intestinal virome in modulating intestinal inflammation and disease. Video Abstract.}, }
@article {pmid35798626, year = {2022}, author = {Martín Legorburo, MJ and Pareja Sierra, T and Martínez Ramírez, M and Martin Alcalde, E and Torralba, M and Rodríguez Solís, J}, title = {[Fecal transplantation for the treatment of Clostridioides difficile recurrent infection].}, journal = {Revista espanola de geriatria y gerontologia}, volume = {57}, number = {4}, pages = {236-237}, doi = {10.1016/j.regg.2022.06.002}, pmid = {35798626}, issn = {1578-1747}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Reinfection ; Treatment Outcome ; }, }
@article {pmid35797794, year = {2022}, author = {Huang, C and Yi, P and Zhu, M and Zhou, W and Zhang, B and Yi, X and Long, H and Zhang, G and Wu, H and Tsokos, GC and Zhao, M and Lu, Q}, title = {Erratum to "Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial" [J. Autoimmun. 130, June 2022, 102844].}, journal = {Journal of autoimmunity}, volume = {131}, number = {}, pages = {102862}, doi = {10.1016/j.jaut.2022.102862}, pmid = {35797794}, issn = {1095-9157}, }
@article {pmid35797768, year = {2022}, author = {Luo, Y and Zhang, Y and Han, X and Yuan, Y and Zhou, Y and Gao, Y and Yu, H and Zhang, J and Shi, Y and Duan, Y and Zhao, X and Yan, S and Hao, H and Dai, C and Zhao, S and Shi, J and Li, W and Zhang, S and Xu, W and Fang, N and Gong, Y and Li, Y}, title = {Akkermansia muciniphila prevents cold-related atrial fibrillation in rats by modulation of TMAO induced cardiac pyroptosis.}, journal = {EBioMedicine}, volume = {82}, number = {}, pages = {104087}, pmid = {35797768}, issn = {2352-3964}, mesh = {Adolescent ; Akkermansia ; Animals ; *Atrial Fibrillation ; Cross-Sectional Studies ; Humans ; Methylamines ; Mice ; Pyroptosis ; RNA, Ribosomal, 16S/genetics ; Rats ; }, abstract = {BACKGROUND: Cold exposure is one of the most important risk factors for atrial fibrillation (AF), and closely related to the poor prognosis of AF patients. However, the mechanisms underlying cold-related AF are poorly understood.<br><br>METHODS: Various techniques including 16S rRNA gene sequencing, fecal microbiota transplantation, and electrophysiological examination were used to determine whether gut microbiota dysbiosis promotes cold-related AF. Metabonomics were performed to investigate changes in fecal trimethylamine (TMA) and plasma trimethylamine N-oxide (TMAO) during cold exposure. The detailed mechanism underlying cold-related AF were examined in vitro. Transgenic mice were constructed to explore the role of pyroptosis in cold-related AF. The human cohort was used to evaluate the correlation between A. muciniphila and cold-related AF.<br><br>FINDINGS: We found that cold exposure caused elevated susceptibility to AF and reduced abundance of Akkermansia muciniphila (A. muciniphila) in rats. Intriguingly, oral supplementation of A. muciniphila ameliorated the pro-AF property induced by cold exposure. Mechanistically, cold exposure disrupted the A. muciniphila, by which elevated the level of trimethylamine N-oxide (TMAO) through modulation of the microbial enzymes involved in trimethylamine (TMA) synthesis. Correspondingly, progressively increased plasma TMAO levels were validated in human subjects during cold weather. Raised TMAO enhanced the infiltration of M1 macrophages in atria and increased the expression of Casp1-p20 and cleaved-GSDMD, ultimately causing atrial structural remodeling. Furthermore, the mice with conditional deletion of caspase1 exhibited resistance to cold-related AF. More importantly, a cross-sectional clinical study revealed that the reduction of A. muciniphila abundance was an independent risk factor for cold-related AF in human subjects.<br><br>INTERPRETATION: Our findings revealed a novel causal role of aberrant gut microbiota and metabolites in pathogenesis of cold-related AF, which raises the possibility of selectively targeting microbiota and microbial metabolites as a potential therapeutic strategy for cold-related AF.<br><br>FUNDING: This work was supported by grants from the State Key Program of National Natural Science Foundation of China (No.81830012), and National Natural Science Foundation of China (No.82070336, No.81974024), Youth Program of the National Natural Science Foundation of China (No.81900374, No.81900302), and Excellent Young Medical Talents supporting project in the First Affiliated Hospital of Harbin Medical University (No. HYD2020YQ0001).}, }
@article {pmid35797284, year = {2022}, author = {Naseem, Z and Ayub, M and Shah, SA and Ali, SA and Abidi, SH}, title = {Viral infections in Pakistan: prevalence, factors affecting spread, and recommendations for control.}, journal = {Journal of infection in developing countries}, volume = {16}, number = {6}, pages = {913-926}, doi = {10.3855/jidc.15078}, pmid = {35797284}, issn = {1972-2680}, mesh = {Humans ; Pakistan/epidemiology ; Prevalence ; *Virus Diseases/epidemiology/prevention &amp; control ; *Viruses ; }, abstract = {Pakistan is endemic to a number of viral infections, owing to its humid climate, topographical variation, soaring population, and lack of education and awareness. These viruses may have several different modes of transmission, including respiratory or airborne transmission, sexual transmission, blood-borne, fecal-oral transmission, vector-borne transmission, and transmission following an organ transplant. Although several different microorganisms are responsible for causing these infections, a few viruses are found more commonly in Pakistan and are primarily responsible for causing infections. In this study, we present a review of the most recent studies on different viruses, transmitted through various transmission routes, found commonly in Pakistan, along with the prevalence of each, and recommend control measures required against these viruses.}, }
@article {pmid35796402, year = {2022}, author = {Chen, C and Liang, H and Wang, J and Ren, G and Li, R and Cui, ZG and Zhang, C}, title = {Heterophyllin B an Active Cyclopeptide Alleviates Dextran Sulfate Sodium-Induced Colitis by Modulating Gut Microbiota and Repairing Intestinal Mucosal Barrier via AMPK Activation.}, journal = {Molecular nutrition &amp; food research}, volume = {66}, number = {17}, pages = {e2101169}, doi = {10.1002/mnfr.202101169}, pmid = {35796402}, issn = {1613-4133}, mesh = {AMP-Activated Protein Kinases ; Animals ; *Colitis/chemically induced/drug therapy/pathology ; *Colitis, Ulcerative/chemically induced/drug therapy ; Colon ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Dysbiosis/drug therapy/pathology ; *Gastrointestinal Microbiome ; Humans ; Mice ; Mice, Inbred C57BL ; *Peptides, Cyclic/pharmacology ; }, abstract = {SCOPE: Advances in pathology broaden the perception of the intimate interaction between gut microbiota dysbiosis and the pathogenesis of ulcerative colitis (UC), but the potential modulating roles remain to be elucidated.<br><br>METHODS AND RESULTS: DSS-induced colitis is used to investigate the effect of Heterophyllin B (HB), a typical active cyclopeptide extracted from Pseudostellaria heterophylla, on colitis and gut microbiota. Administration of HB substantially mitigates the symptoms of UC as evidenced by increasing body weight and colon length, as well as decreased macrophages infiltration in the colon. Meanwhile, HB significantly alleviates intestinal mucosal barrier dysfunction by reducing the production of inflammatory cytokines, while all the mentioned beneficial effects are significantly eliminated by co-treatment with compound C, a selective AMPK inhibitor. In addition, 16S rDNA gene analyses and fecal microbiota transplantation also reveal that HB dramatically prevents against UC by reshaping intestinal dysbiosis, especially elevates the relative abundance of Akkermansia muciniphila.<br><br>CONCLUSION: These findings illustrate that HB prominently improves intestinal epithelial homeostasis via activating AMPK and ameliorates the colonic inflammation in a gut microbiota-dependent manner, which provide evidence for microbial contribution to UC pathogenesis and suggesting a novel approach for colitis prevention.}, }
@article {pmid35795291, year = {2022}, author = {Tan, XY and Xie, YJ and Liu, XL and Li, XY and Jia, B}, title = {A Systematic Review and Meta-Analysis of Randomized Controlled Trials of Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2022}, number = {}, pages = {8266793}, pmid = {35795291}, issn = {1741-427X}, abstract = {OBJECTIVES: Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of the gastrointestinal tract, and its prevalence is increasing worldwide. Fecal microbiota transplantation (FMT) is an emerging therapy that modifies the patient's gut microbiota by transplanting feces from a healthy donor to achieve disease remission. However, its efficacy and safety need to be further investigated.<br><br>METHODS: PubMed, the Cochrane Library, Web of Science, Embase, and Google Scholar databases (up to 8th November 2021) were searched and literature was screened by title and abstract as well as full text. The primary outcome was clinical remission, with the clinical response as a secondary outcome. Risk ratios (RR) with 95% confidence intervals (CI) were reported.<br><br>RESULTS: A total of 14 trials were included in this study. In terms of clinical remission, FMT had a significant effect compared to placebo (RR&#x2009;=&#x2009;1.44, 95 CI%: 1.03 to 2.02, I [2]&#x2009;=&#x2009;38%, P=0.03), with no significant risk of study heterogeneity. Moreover, FMT led to significant results in clinical response compared to placebo with moderate between-study heterogeneity (RR&#x2009;=&#x2009;1.34, 95 CI%: 0.92 to 1.94, I [2]&#x2009;=&#x2009;51%, P=0.12). Subgroup analysis showed a higher clinical remission for fresh fecal FMT (40.9%) than that for frozen fecal FMT (32.2%); the efficacy of gastrointestinal (GI) pretreatment, the severity of disease, route of administration, and the donor selection remain unclear and require more extensive study. Safety analysis concluded that most adverse events were mild and self-resolving. The microbiological analysis found that the patient's gut microbiota varied in favor of the donor, with increased flora diversity and species richness.<br><br>CONCLUSION: FMT is a safe, effective, and well-tolerated therapy. Studies have found that fresh fecal microbiota transplant can increase clinical remission rates. However, more randomized controlled trials and long-term follow-ups are needed to assess its long-term effectiveness and safety.}, }
@article {pmid35794639, year = {2022}, author = {Hoque, MN and Rahman, MS and Islam, T and Sultana, M and Crandall, KA and Hossain, MA}, title = {Induction of mastitis by cow-to-mouse fecal and milk microbiota transplantation causes microbiome dysbiosis and genomic functional perturbation in mice.}, journal = {Animal microbiome}, volume = {4}, number = {1}, pages = {43}, pmid = {35794639}, issn = {2524-4671}, abstract = {BACKGROUND: Mastitis pathogenesis involves a wide range of opportunistic and apparently resident microorganims including bacteria, viruses and archaea. In dairy animals, microbes reside in the host, interact with environment and evade the host immune system, providing a potential for host-tropism to favor mastitis pathogenesis. To understand the host-tropism phenomena of bovine-tropic mastitis microbiomes, we developed a cow-to-mouse mastitis model.<br><br>METHODS: A cow-to-mouse mastitis model was established by fecal microbiota transplantation (FMT) and milk microbiota transplantation (MMT) to pregnant mice to assess microbiome dysbiosis and genomic functional perturbations through shotgun whole metagenome sequencing (WMS) along with histopathological changes in mice mammary gland and colon tissues.<br><br>RESULTS: The cow-to-mouse FMT and MMT from clinical mastitis (CM) cows induced mastitis syndromes in mice as evidenced by histopathological changes in mammary gland and colon tissues. The WMS of 24 samples including six milk (CM&#x2009;=&#x2009;3, healthy; H&#x2009;=&#x2009;3), six fecal (CM&#x2009;=&#x2009;4, H&#x2009;=&#x2009;2) samples from cows, and six fecal (CM&#x2009;=&#x2009;4, H&#x2009;=&#x2009;2) and six mammary tissue (CM&#x2009;=&#x2009;3, H&#x2009;=&#x2009;3) samples from mice generating 517.14 million reads (average: 21.55 million reads/sample) mapped to 2191 bacterial, 94 viral and 54 archaeal genomes. The Kruskal-Wallis test revealed significant differences (p&#x2009;=&#x2009;0.009) in diversity, composition, and relative abundances in microbiomes between CM- and H-metagenomes. These differences in microbiome composition were mostly represented by Pseudomonas aeruginosa, Lactobacillus crispatus, Klebsiella oxytoca, Enterococcus faecalis, Pantoea dispersa in CM-cows (feces and milk), and Muribaculum spp., Duncaniella spp., Muribaculum intestinale, Bifidobacterium animalis, Escherichia coli, Staphylococcus aureus, Massilia oculi, Ralstonia pickettii in CM-mice (feces and mammary tissues). Different species of Clostridia, Bacteroida, Actinobacteria, Flavobacteriia and Betaproteobacteria had a strong co-occurrence and positive correlation as the indicator species of murine mastitis. However, both CM cows and mice shared few mastitis-associated microbial taxa (1.14%) and functional pathways regardless of conservation of mastitis syndromes, indicating the higher discrepancy in mastitis-associated microbiomes among lactating mammals.<br><br>CONCLUSIONS: We successfully induced mastitis by FMT and MMT that resulted in microbiome dysbiosis and genomic functional perturbations in mice. This study induced mastitis in a mouse model through FMT and MMT, which might be useful for further studies- focused on pathogen(s) involved in mastitis, their cross-talk among themselves and the host.}, }
@article {pmid35794548, year = {2022}, author = {Su, XH and Li, WP and Lin, Q and Zheng, XJ and Fang, T and Jiang, Y and Peng, FH}, title = {Case report: a special case of cryptococcal infection-related inflammatory syndrome in a non-HIV infected and non-transplant patient.}, journal = {BMC neurology}, volume = {22}, number = {1}, pages = {247}, pmid = {35794548}, issn = {1471-2377}, support = {82071265//national natural science foundation of china/ ; 202102010288//the Science and Technology Program of Guangzhou, China/ ; 2021A1515110231//Guangdong Basic and Applied Basic Research Foundation/ ; }, mesh = {Adult ; Antifungal Agents/therapeutic use ; *Cryptococcosis/complications/diagnosis/drug therapy ; *Cryptococcus neoformans ; Humans ; Male ; *Meningitis, Cryptococcal/complications/diagnosis/drug therapy ; *Meningoencephalitis/complications ; Syndrome ; Voriconazole ; }, abstract = {BACKGROUND: Cryptococcal meningoencephalitis (CM) is a severe infection of central nervous system with high mortality and morbidity. Infection-related inflammatory syndrome is a rare complication of CM. Herein, we report a case of CM complicated by infection-related inflammatory syndrome.<br><br>CASE PRESENTATION: A 42-year-old man with chronic hepatitis B presented with a 3-day history of aphasia and left hemiparesis at an outside medical facility. The brain magnetic resonance imaging (MRI) showed symmetric and confluent hyperintense signal abnormalities mainly located in the basal ganglia, internal capsule, external capsule, periventricular, corona radiata, frontal and temporal lobes. Cerebrospinal fluid (CSF) examinations revealed elevated leukocyte and protein. India ink staining was positive for Cryptococcus. CSF culture and metagenomic next-generation sequencing (mNGS) confirmed Cryptococcus neoformans. Initial response was observed with intravenous fluconazole (400&#x2009;mg per day). However, 11&#x2009;days later, he developed impaired consciousness and incontinence of urine and feces. A repeat brain MRI showed the lesions were progressive and enlarged. The patient was referred to our department at this point of time. Repeat CSF analysis (India ink staining, culture and mNGS) re-confirmed Cryptococcus. However, clinical worsening after initial improvement, laboratory examinations and brain MRI findings suggested a diagnosis of infection-related inflammatory syndrome. Therefore, a combination of corticosteroids and antifungal therapy was initiated. At follow-up, a complete neurological recovery without any relapse was documented. The repeat brain MRI showed complete resolution of the previous lesions.<br><br>CONCLUSIONS: This case demonstrated that cryptococcal inflammatory syndromes must be suspected in cases of CM if an otherwise unexplained clinical deterioration is observed after initial recovery. The same can happen even before the primary infection is controlled. Thus, timely identification and prompt treatment is vital to reduce the mortality and disability of CM. The administration of corticosteroids in combination with antifungal therapy is an effective strategy in such cases. Clinical course and treatment process of the patient. Hemiparalysis and aphasia improved after the initiation of antifungal treatment. However, the patient developed impaired consciousness companied by deterioration of brain MRI findings. He was treated with adjunctive glucocorticoid taper therapy consisting of dexamethasone (20&#x2009;mg/day, intravenously) for 1&#x2009;week followed by oral prednisone 1&#x2009;mg/kg/day, tapered based on clinical and radiological response, along with amphotericin B (0.6&#x2009;mg/kg/day, intravenously), voriconazole (400&#x2009;mg/day in 2 divided doses, intravenously), and 5-flucytosine (100&#x2009;mg/kg/day in 4 divided doses, orally). Two weeks later, his symptoms improved significantly. After discharge, he began oral voriconazole for consolidation and maintenance therapy for 8&#x2009;weeks and 9&#x2009;months respectively. He recovered without any neurological sequelae at 6-month follow-up. Note: MRI&#x2009;=&#x2009;magnetic resonance imaging.}, }
@article {pmid35792193, year = {2022}, author = {Avolio, E and Olivito, I and Rosina, E and Romano, L and Angelone, T and De Bartolo, A and Scimeca, M and Bellizzi, D and D'Aquila, P and Passarino, G and Alò, R and Facciolo, RM and Bagni, C and De Lorenzo, A and Canonaco, M}, title = {Modifications of Behavior and Inflammation in Mice Following Transplant with Fecal Microbiota from Children with Autism.}, journal = {Neuroscience}, volume = {498}, number = {}, pages = {174-189}, doi = {10.1016/j.neuroscience.2022.06.038}, pmid = {35792193}, issn = {1873-7544}, mesh = {Animals ; *Autism Spectrum Disorder ; *Autistic Disorder ; Child ; Disease Models, Animal ; Female ; Humans ; Inflammation ; Mice ; *Microbiota ; Pregnancy ; Valproic Acid ; }, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder displaying the modification of complex human behaviors, characterized by social interaction impairments, stereotypical/repetitive activities and emotional dysregulation. In this study, fecal microbiota transplant (FMT) via gavage from autistic children donors to mice, led to the colonization of ASD-like microbiota and autistic behaviors compared to the offspring of pregnant females exposed to valproic acid (VPA). Such variations seemed to be tightly associated with increased populations of Tenericutes plus a notable reduction (p < 0.001) of Actinobacteria and Candidatus S. in the gastrointestinal region of FMT mice as compared to controls. Indeed altered behaviors of FMT mice was reported when evaluated in the different maze tests (light dark, novel object, three chamber tests, novel cage test). Contextually, FMT accounted for elevated expression levels of the pro-inflammatory factors IL-1β, IL-6, COX-1 and TNF-α in both brain and small intestine. Villous atrophy and inflammatory infiltration (Caspase 3 and Ki67) were increased in the small intestine of FMT and VPA mice compared to controls. Moreover, the observed FMT-dependent alterations were linked to a decrease in the methylation status. Overall, findings of the present study corroborate a key role of gut microbiota in ASD. However, further investigations are required before any possible manipulation of gut bacteria with appropriate diets or probiotics can be conducted in ASD individuals.}, }
@article {pmid35791946, year = {2022}, author = {Xu, HJ and Wang, L and Chen, BD and Zhao, LD}, title = {[Fecal Microbiota Transplantation:Traditional Chinese Medicine Meets Western Medicine].}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {44}, number = {3}, pages = {472-476}, doi = {10.3881/j.issn.1000-503X.13774}, pmid = {35791946}, issn = {1000-503X}, mesh = {*Clostridium Infections/therapy ; *Fecal Microbiota Transplantation/methods ; Feces ; Humans ; Medicine, Chinese Traditional ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapy of transplanting the functional flora from the feces of a healthy donor into the gastrointestinal tract of a patient to reconstruct the normal flora.The application of FMT in western medicine dates from the 1950s.After decades of development,the efficacy of FMT has been proven in a variety of diseases.The record of FMT in traditional Chinese medicine (TCM) dates early from the 3rd century A.D.,and relevant theories have been recorded in many TCM works in the past dynasties.FMT as a therapy that has been written into guidelines has been accepted by some countries and regions such as the United States and the United Kingdom in the treatment of Clostridium difficile infection,and its clinical indications are expanding.TCM and western medicine,with different medical thoughts,meet in the application of FMT.Exploring a normative and effective FMT procedure reflects not only the patient-centered principle but also the mutual promotion of TCM and western medicine.}, }
@article {pmid35787664, year = {2022}, author = {Zuo, T}, title = {'Dark matter' beyond the bacteria in faecal microbiota transplantation.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {19}, number = {10}, pages = {624}, pmid = {35787664}, issn = {1759-5053}, mesh = {*Bacteria ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; }, }
@article {pmid35787489, year = {2022}, author = {Chambers, J and Appleton, A and Dudley, C}, title = {Pancreatic insufficiency as a complication of type 1 diabetes causing enteric hyperoxaluria in a transplant kidney.}, journal = {BMJ case reports}, volume = {15}, number = {7}, pages = {}, pmid = {35787489}, issn = {1757-790X}, mesh = {*Acute Kidney Injury/complications ; *Diabetes Mellitus, Type 1/complications ; *Exocrine Pancreatic Insufficiency/complications ; Humans ; *Hyperoxaluria/complications/diagnosis ; Kidney ; Oxalates/urine ; Pancreatic Elastase ; }, abstract = {A kidney transplant recipient with a medical history of type 1 diabetes mellitus (T1DM) presents to the clinic with an acute kidney injury (AKI) and diarrhoea. Kidney biopsy found deposition of focal oxalate crystals, and further investigation revealed a raised 24-hour urinary oxalate and reduced faecal elastase. Therefore, we present a case of acute oxalate nephropathy (AON) secondary to enteric hyperoxaluria as a result of pancreatic insufficiency caused by T1DM. T1DM is a common cause of end-stage renal failure and exocrine pancreatic insufficiency. Therefore, AON secondary to enteric hyperoxaluria should be considered in patients with a transplant AKI. Earlier testing of 24-hour urinary oxalate and faecal elastase could generate diagnosis before biopsy results and allow commencement of pancreatic replacement therapy earlier to avoid permanent loss of kidney function.}, }
@article {pmid35787106, year = {2022}, author = {Rodriguez Paris, V and Wong, XYD and Solon-Biet, SM and Edwards, MC and Aflatounian, A and Gilchrist, RB and Simpson, SJ and Handelsman, DJ and Kaakoush, NO and Walters, KA}, title = {The interplay between PCOS pathology and diet on gut microbiota in a mouse model.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2085961}, pmid = {35787106}, issn = {1949-0984}, mesh = {Animals ; Diet ; Disease Models, Animal ; Feces ; Female ; *Gastrointestinal Microbiome/physiology ; Humans ; Mice ; *Polycystic Ovary Syndrome ; }, abstract = {The gut microbiome has been implicated in polycystic ovary syndrome (PCOS) pathophysiology. PCOS is a disorder with reproductive, endocrine and metabolic irregularities, and several studies report that PCOS is associated with a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, as alterations in macronutrient composition impact the balance of gut microbial communities. This study investigated the interplay between macronutrient balance and PCOS on the gut microbiome of control and dihydrotestosterone (DHT)-induced PCOS-like mice exposed to diets that varied in protein (P), carbohydrate (C) and fat (F) content. The amount of dietary P, C and F consumed significantly altered alpha (α) and beta (β) diversity of the gut microbiota of control and PCOS-like mice. However, α-diversity between control and PCOS-like mice on the same diet did not differ significantly. In contrast, β-diversity was significantly altered by PCOS pathology. Further analysis identified an operational taxonomic unit (OTU) within Bacteroides (OTU3) with 99.2% similarity to Bacteroides acidifaciens, which is inversely associated with obesity, to be significantly decreased in PCOS-like mice. Additionally, this study investigated the role of the gut microbiome in the development of PCOS traits, whereby PCOS-like mice were transplanted with healthy fecal microbiota from control mice. Although the PCOS gut microbiome shifted toward that of control mice, PCOS traits were not ameliorated. Overall, these findings demonstrate that while diet exerts a stronger influence over gut microbiota diversity than PCOS pathology, overall gut microbiota composition is affected by PCOS pathology.}, }
@article {pmid35785728, year = {2022}, author = {Xu, Q and Li, D and Chen, J and Yang, J and Yan, J and Xia, Y and Zhang, F and Wang, X and Cao, H}, title = {Crosstalk between the gut microbiota and postmenopausal osteoporosis: Mechanisms and applications.}, journal = {International immunopharmacology}, volume = {110}, number = {}, pages = {108998}, doi = {10.1016/j.intimp.2022.108998}, pmid = {35785728}, issn = {1878-1705}, mesh = {Aged ; Fecal Microbiota Transplantation/adverse effects ; Female ; *Gastrointestinal Microbiome ; Humans ; *Osteoporosis, Postmenopausal/etiology/therapy ; Prebiotics ; *Probiotics/pharmacology/therapeutic use ; }, abstract = {Postmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. The number of people suffering from PMO has increased over the years because of the rapidly aging population worldwide. However, several pharmacological agents for the treatment of PMO have many safety risks and impose a heavy financial burden to patients and society. In recent years, the "gut-bone" axis has been proposed as a new approach in the prevention and treatment of PMO. This paper reviews the relationship between the gut microbiota and PMO, which mainly includes the underlying mechanisms between hormones, immunity, nutrient metabolism, metabolites of the gut microbiota and intestinal permeability, and explores the possible role of the gut microbiota in these processes. Finally, we discuss the therapeutic effects of diet, prebiotics, probiotics, and fecal microbiota transplantation on the gut microbiota.}, }
@article {pmid35785254, year = {2022}, author = {Xie, C and Zhu, X and Xu, B and Niu, Y and Zhang, X and Ma, L and Yan, X}, title = {Integrated analysis of multi-tissues lipidome and gut microbiome reveals microbiota-induced shifts on lipid metabolism in pigs.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {10}, number = {}, pages = {280-293}, pmid = {35785254}, issn = {2405-6383}, abstract = {Lipid metabolism is very important for meat quality in pigs. Accumulating evidence shows that gut microbiota can contribute to this physiological process. However, the gut microbiota that function in lipid metabolism and adipogenesis remains unclear. Here, we compared the characteristics of fat deposition and gut microbial community between Laiwu pigs and Duroc × (Landrace × Yorkshire) (DLY) pigs. Fecal microbiota transplantation (FMT) was performed to determine the possible impact of gut microbiota on lipid metabolism in pigs. An integrated analysis of the gut microbiome and lipidome of the small intestine, plasma, and liver was conducted to investigate the effects of FMT on host lipid metabolism. The comparative analysis of the gut microbiome showed higher abundance of Bacteroidetes (P = 0.0018) while lower abundance of Firmicutes (P = 0.012) in Laiwu pigs, and the microbial composition can be transferred from Laiwu pigs into DLY pigs. Transmission electron microscope and Oil red-O staining were performed to analyze the effects of FMT on lipid deposition in liver, the main target organ for lipid metabolism. The results showed that FMT significantly increased the number of lipid droplets (P = 0.0035) and lipid accumulation (P = 0.0026) in liver. Furthermore, integrated multi-tissues lipidome analysis demonstrated that the fatty acyls and glycerophospholipids were significantly increased (P < 0.01) in intestine and liver, while glycerolipids and fatty acyls were reduced (P < 0.01) in plasma. In the small intestine, FMT increased (P < 0.01) the relative abundance of polyketides and prenol lipids but reduced (P < 0.01) the saccharolipids. Correlation analysis revealed the potential interactions between microbiota and lipid metabolites. Together, our results indicated that the gut microbiota may regulate the lipid metabolism and enhance the accumulation of lipid droplets in the liver of pigs.}, }
@article {pmid35784625, year = {2022}, author = {Vasavada, S and Panneerselvam, K and Amin, R and Varatharajalu, K and Okhuysen, PC and Oliva, ICG and Wang, J and Grivas, P and Thomas, AS and Wang, Y}, title = {Clostridioides difficile infection in cancer patients receiving immune checkpoint inhibitors.}, journal = {Annals of gastroenterology}, volume = {35}, number = {4}, pages = {393-399}, pmid = {35784625}, issn = {1108-7471}, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but are associated with immune-mediated diarrhea and colitis (IMDC). Clostridioides difficile infection (CDI) can cause infectious diarrhea with overlapping symptoms. Thus, we sought to elucidate the characteristics of CDI in patients treated with ICI, in the context of IMDC.<br><br>METHODS: We conducted a retrospective, single-center study of adult cancer patients (N=421) with ICI exposure from 2015-2020 and a positive stool nucleic acid amplification test and/or enzyme immunoassay for CDI. Baseline characteristics, treatments, and outcomes were compared between patients with and without concurrent IMDC.<br><br>RESULTS: Forty-one eligible patients were included, 27 with concurrent IMDC and 14 without. Twenty-seven patients were taking programmed death-1 or its ligand inhibitors and 14 were taking cytotoxic T-lymphocyte-associated antigen 4 inhibitors. Patients with concurrent CDI and IMDC had a longer symptom duration (20 vs. 5 days, P=0.003) and a higher rate of grade 3-4 diarrhea (41% vs. 7%, P=0.033). Among patients with concurrent IMDC, preceding antibiotics (P=0.050) and proton pump inhibitors (PPI) (P=0.038) were used more frequently among individuals who developed CDI after immunosuppressant exposure. Thirty-eight patients received antibiotics for CDI, while 5 required fecal microbiota transplantation for concurrent CDI &amp; IMDC.<br><br>CONCLUSIONS: CDI is common in ICI-treated cancer patients, especially those with IMDC requiring immunosuppressants. Antibiotics did not alter the need for immunosuppressants in those with concurrent IMDC. Use of PPI and antibiotics while receiving immunosuppressants for IMDC was associated with a greater risk of CDI. Further large-scale studies are warranted to clarify the role of CDI, antibiotics and immunosuppression treatment in IMDC patients.}, }
@article {pmid35784367, year = {2022}, author = {Johnson, S and Hoch, JS and Halabi, WJ and Ko, J and Nolta, J and Dave, M}, title = {Mesenchymal Stem/Stromal Cell Therapy Is More Cost-Effective Than Fecal Diversion for Treatment of Perianal Crohn's Disease Fistulas.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {859954}, pmid = {35784367}, issn = {1664-3224}, support = {K08 DK110421/DK/NIDDK NIH HHS/United States ; }, mesh = {Cost-Benefit Analysis ; *Crohn Disease/complications/therapy ; Decision Trees ; *Fistula/complications ; Humans ; *Mesenchymal Stem Cell Transplantation ; Treatment Outcome ; }, abstract = {Crohn's disease (CD) is an inflammatory bowel disease with increasing incidence and prevalence worldwide. Perianal fistulas are seen in up to 26% of CD patients and are often refractory to medical therapy. Current treatments for CD perianal fistulas (pCD) include antibiotics, biologics, and for refractory cases, fecal diversion (FD) with ileostomy or colostomy. Mesenchymal stem/stromal cell therapy (MSCs) is a new modality that have shown efficacy in treating pCD. MSCs locally injected into pCD can lead to healing, and a phase III clinical trial (ADMIRE-CD) showed 66% clinical response, leading to approval of MSCs (Alofisel, Takeda) in the European Union. It is unclear if MSCs would be more cost-effective than the current standard of FD. We therefore developed a decision tree model to determine the cost-effectiveness of MSCs compared to FD for pCD. Our study showed that both autologous and allogeneic MSCs are more cost-effective than FD in an academic medical center and even in a worst-case scenario with 100% chance of all complications for MSCs treatment and 0% chance of complications for FD, both allogeneic and autologous MSCs are still cost saving compared to FD.}, }
@article {pmid35783604, year = {2022}, author = {Rashed, R and Valcheva, R and Dieleman, LA}, title = {Manipulation of Gut Microbiota as a Key Target for Crohn's Disease.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {887044}, pmid = {35783604}, issn = {2296-858X}, abstract = {Crohn's disease (CD) is an inflammatory bowel disease (IBD) sub-type characterized by transmural chronic inflammation of the gastrointestinal tract. Research indicates a complex CD etiology involving genetic predisposition and immune dysregulation in response to environmental triggers. The chronic mucosal inflammation has been associated with a dysregulated state, or dysbiosis, of the gut microbiome (bacteria), mycobiome (fungi), virome (bacteriophages and viruses), and archeaome (archaea) further affecting the interkingdom syntrophic relationships and host metabolism. Microbiota dysbiosis in CD is largely described by an increase in facultative anaerobic pathobionts at the expense of strict anaerobic Firmicutes, such as Faecalibacterium prausnitzii. In the mycobiome, reduced fungal diversity and fungal-bacteria interactions, along with a significantly increased abundance of Candida spp. and a decrease in Saccharomyces cerevisiae are well documented. Virome analysis also indicates a significant decrease in phage diversity, but an overall increase in phages infecting bacterial groups associated with intestinal inflammation. Finally, an increase in methanogenic archaea such as Methanosphaera stadtmanae exhibits high immunogenic potential and is associated with CD etiology. Common anti-inflammatory medications used in CD management (amino-salicylates, immunomodulators, and biologics) could also directly or indirectly affect the gut microbiome in CD. Other medications often used concomitantly in IBD, such as antibiotics, antidepressants, oral contraceptives, opioids, and proton pump inhibitors, have shown to alter the gut microbiota and account for increased susceptibility to disease onset or worsening of disease progression. In contrast, some environmental modifications through alternative therapies including fecal microbiota transplant (FMT), diet and dietary supplements with prebiotics, probiotics, and synbiotics have shown potential protective effects by reversing microbiota dysbiosis or by directly promoting beneficial microbes, together with minimal long-term adverse effects. In this review, we discuss the different approaches to modulating the global consortium of bacteria, fungi, viruses, and archaea in patients with CD through therapies that include antibiotics, probiotics, prebiotics, synbiotics, personalized diets, and FMT. We hope to provide evidence to encourage clinicians and researchers to incorporate these therapies into CD treatment options, along with making them aware of the limitations of these therapies, and indicate where more research is needed.}, }
@article {pmid35783418, year = {2022}, author = {Xiang, M and Zheng, L and Pu, D and Lin, F and Ma, X and Ye, H and Pu, D and Zhang, Y and Wang, D and Wang, X and Zou, K and Chen, L and Zhang, Y and Sun, Z and Zhang, T and Wu, G}, title = {Intestinal Microbes in Patients With Schizophrenia Undergoing Short-Term Treatment: Core Species Identification Based on Co-Occurrence Networks and Regression Analysis.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {909729}, pmid = {35783418}, issn = {1664-302X}, abstract = {Schizophrenia, a common mental disorder, has a tremendous impact on the health and economy of people worldwide. Evidence suggests that the microbial-gut-brain axis is an important pathway for the interaction between the gut microbiome and the development of schizophrenia. What is not clear is how changes in the gut microbiota composition and structure during antipsychotic treatment improve the symptoms of schizophrenia. In this study, 25 patients with schizophrenia were recruited. Their fecal samples were collected before and after hospital treatment for 14-19 days. The composition and structure of the intestinal microbiota were evaluated by 16S rRNA sequencing analysis, and the results showed significant differences in fecal microbiota before and after treatment. Firmicutes (relative abundances of 82.60 and 86.64%) and Gemminger (relative abundances of 14.17 and 13.57%) were the first dominant species at the phylum and genus levels, respectively. The random forest algorithm and co-occurrence network analysis demonstrated that intestinal flora (especially the core species ASV57) could be used as biomarkers to distinguish different clinical states and match treatment regimens accordingly. In addition, after fecal microbiota transplantation, antibiotic-treated recipient mice showed multiple behavioral improvements. These included decreased psychomotor hyperactivity, increased social interaction, and memory. In conclusion, this study suggests that differences in the composition and structure of gut microbiota after treatment are associated with the development and severity of schizophrenia. Results may provide a potential target for the treatment of this disorder.}, }
@article {pmid35783298, year = {2022}, author = {Pan, ZY and Zhong, HJ and Huang, DN and Wu, LH and He, XX}, title = {Beneficial Effects of Repeated Washed Microbiota Transplantation in Children With Autism.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {928785}, pmid = {35783298}, issn = {2296-2360}, abstract = {OBJECTIVE: While fecal microbiota transplantation is demonstrated to improve symptoms of autism spectrum disorder (ASD), it remains unclear whether additional treatment courses yield better results. This study sought to evaluate the efficacy of repeated washed microbiota transplantation (WMT) in children with ASD.<br><br>METHODS: Retrospective data from children who were serially treated with WMT, including ASD symptoms, sleep disorders, gastrointestinal (GI) symptoms, and white blood cell (WBC) and globulin levels were obtained. The effect of WMT on children with ASD and whether additional WMT courses led to a further improvement in symptoms were assessed.<br><br>RESULTS: Aberrant Behavior Checklist (ABC), Childhood Autism Rating Scale, and Sleep Disturbance Scale for Children (SDSC) scores, the proportion of children with constipation and abnormal fecal forms, and WBC and globulin levels were all significantly lower in ASD children after WMT. More WMT treatment courses led to significantly lower scores on the ABC and SDSC.<br><br>CONCLUSION: WMT significantly improved ASD and GI symptoms and sleep disorders in children with ASD, and reduced systemic inflammation. Additional WMT courses led to more obvious improvements in ASD symptoms within three treatment courses.}, }
@article {pmid35782138, year = {2022}, author = {Zhu, Y and Xu, Y and Wang, X and Rao, L and Yan, X and Gao, R and Shen, T and Zhou, Y and Kong, C and Zhou, L}, title = {Probiotic Cocktail Alleviates Intestinal Inflammation Through Improving Gut Microbiota and Metabolites in Colitis Mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {886061}, pmid = {35782138}, issn = {2235-2988}, mesh = {Animals ; Bifidobacterium ; Chromatography, Liquid ; *Colitis/drug therapy/therapy ; Dextran Sulfate/toxicity ; *Gastrointestinal Microbiome/physiology ; Inflammation/therapy ; *Inflammatory Bowel Diseases ; Mice ; Mice, Inbred C57BL ; *Probiotics/therapeutic use ; Tandem Mass Spectrometry ; }, abstract = {The modulation of the gut microbiome has been widely suggested as a promising therapeutic strategy for inflammatory bowel disease (IBD). Here, we established a novel probiotic cocktail to investigate its therapeutic role in acute colitis mice. During dextran sulfate sodium (DSS)-induced colitis, the mice were treated with the probiotic cocktail, fecal microbiota transplantation (FMT) from a healthy mice donor, or 5-aminosalicylic acid (5-ASA), respectively. The inflammatory responses were assessed by symptoms, serum inflammatory factors, and histological scoring. The intestinal barrier function was assessed by detecting tight junction proteins. Gut microbiota and its metabolites were further identified using 16S rDNA sequencing and a liquid chromatograph mass spectrometer (LC-MS/MS). Compared with FMT and 5-ASA treatment, the probiotic cocktail performed better in alleviating symptoms of colitis and decreasing disease activity score and mucosal inflammation. The probiotic cocktail also significantly decreased serum IL-17 level and increased JAM-1 expression in colon. The gut microbiota analysis confirmed that the beneficial effects of the probiotic cocktail were attributed to increasing anti-inflammatory bacteria Akkermansia, Bifidobacterium, and Blautia, while decreasing pro-inflammatory bacteria Parasutterella. The targeted metabolome analysis further indicated a rise in the production of Bifidobacterium-related short-chain fatty acids (SCFAs) such as propanoic acid and isobutyric acid after probiotics treatment. Taken together, the probiotic cocktail effectively alleviated intestinal inflammation through improving gut microbiota and metabolites in colitis mice, suggesting its great potential to be a novel therapeutic approach for IBD patients.}, }
@article {pmid35782123, year = {2022}, author = {Wen, L and Shi, L and Kong, XL and Li, KY and Li, H and Jiang, DX and Zhang, F and Zhou, ZG}, title = {Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {856633}, pmid = {35782123}, issn = {2235-2988}, mesh = {Amino Sugars/metabolism ; Animals ; Forkhead Transcription Factors/metabolism ; *Gastrointestinal Microbiome ; Inflammation/metabolism ; Interleukin-17/metabolism ; Interleukin-6/metabolism ; Mice ; Nucleotides/metabolism ; *Pneumonia ; Pseudomonas aeruginosa ; *Quinolones/metabolism ; RNA, Ribosomal, 16S/genetics ; T-Lymphocytes, Regulatory ; Th17 Cells ; }, abstract = {BACKGROUNDS AND PURPOSE: The theory of "entero-pulmonary axis" proves that pneumonia leads to gut microbiota disturbance and Treg/Th17 immune imbalance. This study is aimed to explore the potential mechanism of fecal microbiota transplantation (FMT) in the treatment of Pseudomonas aeruginosa pneumonia, in order to provide new insights into the treatment of pneumonia.<br><br>METHODS: Pseudomonas aeruginosa and C57/BL6 mice were used to construct the acute pneumonia mouse model, and FMT was treated. Histopathological changes in lung and spleen were observed by HE staining. The expression of CD25, Foxp3 and IL-17 was observed by immunofluorescence. The proportion of Treg and Th17 cells was analyzed by flow cytometry. Serum IL-6, LPS, and IFN-&#x3b3; levels were detected by ELISA. The expression of TNF-&#x3b1;, IFN-&#x3b3;, IL-6, IL-2, Foxp3, IL-17, IL-10, and TGF&#x3b2;1 in lung tissue homogenate was detected by qRT-PCR. 16S rRNA sequencing and non-targeted metabolomics were used to analyze gut microbiota and metabolism.<br><br>RESULTS: Pseudomonas aeruginosa caused the decrease of body weight, food and water intake, lung tissue, and spleen injury in mice with pneumonia. Meanwhile, it caused lung tissue and serum inflammation, and Treg/Th17 cell imbalance in mice with pneumonia. Pseudomonas aeruginosa reduced the diversity and number of gut microbiota in pneumonia mice, resulting in metabolic disorders, superpathway of quinolone and alkylquinolone biosynthesis. It also led to the decrease of 2-heptyl-3-hydroxy-4(1H)-quinolone biosynthesis, and the enrichment of Amino sugar and nucleotide sugar metabolism. FMT with or without antibiotic intervention restored gut microbiota abundance and diversity, suppressed inflammation and tissue damage, and promoted an immunological balance of Treg/Th17 cells in mice with pneumonia. In addition, FMT inhibited the aerobactin biosynthesis, 4-hydroxyphenylacetate degradation, superpathway of lipopolysaccharide biosynthesis and L-arabinose degradation IV function of microbiota, and improved amino sugar and nucleotide sugar metabolism.<br><br>CONCLUSIONS: FMT restored the Treg/Th17 cells' balance and improved inflammation and lung injury in mice with Pseudomonas aeruginosa pneumonia by regulating gut microbiota disturbance and metabolic disorder.}, }
@article {pmid35781423, year = {2022}, author = {Ke, S and Weiss, ST and Liu, YY}, title = {Rejuvenating the human gut microbiome.}, journal = {Trends in molecular medicine}, volume = {28}, number = {8}, pages = {619-630}, pmid = {35781423}, issn = {1471-499X}, support = {U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; RF1 AG067744/AG/NIA NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Industrial advances have caused significant loss of diversity in our gut microbiome, potentially increasing our susceptibility to many diseases. Recently, rewilding the human gut microbiome - that is, bringing it back to an ancestral or preindustrial state (e.g., by transplanting stool material from donors in nonindustrial societies) - has been hotly debated from medical, ethical, and evolutionary perspectives. Here we propose an alternative solution: rejuvenating the human gut microbiome by stool banking and autologous fecal microbiota transplantation, that is, collecting the hosts' stool samples at a younger age when they are at optimal health, and cryopreserving the samples in a stool bank for the hosts' own future use. In this article we discuss the motivation, applications, feasibility, and challenges of this solution.}, }
@article {pmid35779869, year = {2022}, author = {Castillo-Álvarez, F and Marzo-Sola, ME}, title = {Role of the gut microbiota in the development of various neurological diseases.}, journal = {Neurologia}, volume = {37}, number = {6}, pages = {492-498}, doi = {10.1016/j.nrleng.2019.03.026}, pmid = {35779869}, issn = {2173-5808}, mesh = {*Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; *Gastrointestinal Microbiome ; Humans ; *Multiple Sclerosis ; *Nervous System Diseases ; *Neuromyelitis Optica ; *Parkinson Disease ; }, abstract = {INTRODUCTION: In recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined.<br><br>DEVELOPMENT: We review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson's disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis.<br><br>CONCLUSIONS: The body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson's disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids. Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation.}, }
@article {pmid35776638, year = {2022}, author = {Li, X and Wu, P and Zeng, X and Lang, Q and Lin, Y and Huang, H and Qian, P}, title = {Protocol for correlation analysis of the murine gut microbiome and meta-metabolome using 16S rDNA sequencing and UPLC-MS.}, journal = {STAR protocols}, volume = {3}, number = {3}, pages = {101494}, pmid = {35776638}, issn = {2666-1667}, mesh = {Animals ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; DNA, Ribosomal ; *Gastrointestinal Microbiome/genetics ; Metabolome/genetics ; Metabolomics/methods ; Mice ; RNA, Ribosomal, 16S/genetics ; Tandem Mass Spectrometry ; }, abstract = {The gut microbiota and metabolites play pivotal roles in the pathobiology of various diseases. Here, we describe a protocol to profile the gut microbiome and meta-metabolome of a mouse disease model for acute graft-versus-host disease. We describe steps for fecal sample collection and processing for 16S sequencing and UPLC-MS. Finally, we detail the steps for data analysis and exhibit multi-omic associations to correlate with pathology. For complete details on the use and execution of this protocol, please refer to Li et al. (2020).}, }
@article {pmid35776086, year = {2023}, author = {Yang, J and Yang, H and Li, Y}, title = {The triple interactions between gut microbiota, mycobiota and host immunity.}, journal = {Critical reviews in food science and nutrition}, volume = {63}, number = {33}, pages = {11604-11624}, doi = {10.1080/10408398.2022.2094888}, pmid = {35776086}, issn = {1549-7852}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; *Probiotics/therapeutic use ; Prebiotics ; *Neoplasms ; }, abstract = {The gut microbiome is mainly composed of microbiota and mycobiota, both of which play important roles in the development of the host immune system, metabolic regulation, and maintenance of intestinal homeostasis. With the increasing awareness of the pathogenic essence of infectious, immunodeficiency, and tumor-related diseases, the interactions between gut bacteria, fungi, and host immunity have been shown to directly influence the disease process or final therapeutic outcome, and collaborative and antagonistic relationships are commonly found between bacteria and fungi. Interventions represented by probiotics, prebiotics, engineered probiotics, fecal microbiota transplantation (FMT), and drugs can effectively modulate the triple interactions. In particular, traditional probiotics represented by Bifidobacterium and Lactobacillus and next-generation probiotics represented by Akkermansia muciniphila and Faecalibacterium prausnitzii showed a high enrichment trend in the gut of patients with a high response to inflammation remission and tumor immunotherapy, which predicts the potential medicinal value of these beneficial microbial formulations. However, there are bottlenecks in all these interventions that need to be broken. Meanwhile, further unraveling the underlying mechanisms of the "triple interactions" model can guide precise interventions and ultimately improve the efficiency of interventions on the host gut microbiome and immune modulation, thus directly or indirectly improving anti-inflammatory and tumor immunotherapy effects.}, }
@article {pmid35774395, year = {2022}, author = {Lee, SH and Park, HK and Kang, CD and Choi, DH and Park, SC and Park, JM and Nam, SJ and Chae, GB and Lee, KY and Cho, H and Lee, SJ}, title = {High Dose Intramuscular Vitamin D3 Supplementation Impacts the Gut Microbiota of Patients With Clostridioides Difficile Infection.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {904987}, pmid = {35774395}, issn = {2235-2988}, mesh = {Bacteria/genetics ; Cholecalciferol ; *Clostridioides difficile ; *Clostridium Infections/microbiology ; Dietary Supplements ; *Gastrointestinal Microbiome ; Humans ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Vancomycin ; Vitamin D ; *Vitamin D Deficiency/microbiology ; }, abstract = {BACKGROUND AND AIM: Current therapeutic strategies for Clostridioides difficile infections (CDI), including oral vancomycin, metronidazole and fecal microbial transplantation, have limited efficacy and treatment failure may occur in as many as one- third of cases. Recent studies have reported that lower concentrations of 25-hydroxyvitamin D are associated with CDI severity and recurrence. However, there have been no studies on microbiota composition after the administration of vitamin D in patients with CDI. Therefore, our study aimed to compare the microbiota composition between the two groups, including eight CDI-positive patients with vitamin D supplementation and ten CDI-positive patients without vitamin D supplementation by using 16S rRNA microbial profiling.<br><br>METHODS: Twenty subjects were enrolled in this prospective randomized controlled study. One subject dropped out due to lack of contact with the guardian after discharge and one subject dropped out due to withdrawal of consent. Thus, 18 patients with CDI and vitamin D insufficiency (vitamin D level < 17 ng/mL) were divided into two groups: CDI with vitamin D supplementation (n = 8) and CDI without vitamin D supplementation (control: n = 10). Subjects with vitamin D insufficiency were randomized to receive 200,000 IU intramuscular cholecalciferol whereas patients in the control group received only oral vancomycin. Stool samples were obtained twice before vancomycin was administered and eight weeks after treatment; the V3-V4 16S rRNA metagenomic sequencing was performed using EzBioCloud.<br><br>RESULTS: The alpha diversity of the gut microbiota in the recovery state was significantly higher than that in the CDI state. Analysis of bacterial relative abundance showed significantly lower Proteobacteria and higher Lachnospiraceae, Ruminococcaceae, Akkermansiaceae, and Bifidobacteriaceae in the recovery state. When comparing the control and vitamin D treatment groups after eight weeks, increase in alpha diversity and, abundance of Lachnospiraceae, and Ruminococcaceae exhibited the same trend in both groups. A significant increase in Bifidobacteriaceae and Christensenellaceae was observed in the vitamin D group; Proteobacteria abundance was significantly lower in the vitamin D treatment group after eight weeks than that in the control group.<br><br>CONCLUSION: Our study confirmed that the increase in the abundance of beneficial bacteria such as Bifidobacteriaceae, and Christensenellaceae were prominently evident during recovery after administration of a high dose of cholecalciferol. These findings indicate that vitamin D administration may be useful in patients with CDI, and further studies with larger sample sizes are required.}, }
@article {pmid35766805, year = {2023}, author = {El Hage Chehade, N and Ghoneim, S and Shah, S and Chahine, A and Mourad, FH and Francis, FF and Binion, DG and Farraye, FA and Hashash, JG}, title = {Efficacy of Fecal Microbiota Transplantation in the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.}, journal = {Inflammatory bowel diseases}, volume = {29}, number = {5}, pages = {808-817}, doi = {10.1093/ibd/izac135}, pmid = {35766805}, issn = {1536-4844}, mesh = {Adult ; Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy ; Remission Induction ; Randomized Controlled Trials as Topic ; Feces ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been investigated as a treatment option for patients with inflammatory bowel disease with controversial results.We sought to perform a systematic review and meta-analysis to evaluate the benefit of FMT in patients with ulcerative colitis.<br><br>METHODS: Double-blind randomized controlled trials (RCTs) including adult patients with active ulcerative colitis who received either FMT or placebo were eligible for inclusion. Outcomes of interest included the rate of combined clinical and endoscopic remission, endoscopic remission or response, clinical remission or response, and specific adverse events. The results were pooled together using Reviewer Manager 5.4 software. Publication bias was assessed using the Egger's test.<br><br>RESULTS: Six RCTs involving 324 patients were included. Our findings demonstrate that compared with placebo, FMT has significant benefit in inducing combined clinical and endoscopic remission (odds ratio, 4.11; 95% confidence interval, 2.19-7.72; P < .0001). Subgroup analyses of influencing factors showed no differences between pooled or single stool donors (P = .71), fresh or frozen FMT (P = .35), and different routes or frequencies of delivery (P = .80 and .48, respectively). Pre-FMT antibiotics, bowel lavage, concomitant biologic therapy, and topical rectal therapy did not affect combined remission rates (P values of .47, .38, .28, and .40, respectively). Clinical remission or response and endoscopic remission or response were significantly higher in patients who received FMT compared with placebo (P < .05) without any differences in serious or specific adverse events.<br><br>CONCLUSIONS: FMT demonstrated a clinical and endoscopic benefit in the short-term treatment of active ulcerative colitis, with a comparable safety profile to placebo. Future RCTs are required to standardize study protocols and examine data on maintenance therapy.}, }
@article {pmid35766265, year = {2022}, author = {Wang, H and Yao, J and Chen, Y and Wang, Y and Liu, Y and Liao, Y and Liang, Z and Dong, YH and Qu, M and Ge, X and Zhou, X}, title = {Gut dysbacteriosis attenuates resistance to Mycobacterium bovis infection by decreasing cyclooxygenase 2 to inhibit endoplasmic reticulum stress.}, journal = {Emerging microbes &amp; infections}, volume = {11}, number = {1}, pages = {1806-1818}, pmid = {35766265}, issn = {2222-1751}, mesh = {Animals ; Cyclooxygenase 2/genetics/metabolism ; Dysbiosis/microbiology ; Endoplasmic Reticulum Stress ; Mice ; *Mycobacterium bovis ; *Tuberculosis/microbiology ; }, abstract = {The role of gut microbiota has been described as an important influencer of the immune system. Gut-lung axis is critical in the prevention of mycobacterium infection, but the specific mechanism, by which dysbiosis affects tuberculosis, has not been reported. In this study, we attempted to provide more information on how the gut-lung axis contributes to Mycobacterium bovis (M. bovis) infection. Mice are pre-treated with broad-spectrum antibiotics cocktail (Abx) to induce gut dysbiosis. Interestingly, dysbiosis of microbes showed a significant increase in the bacterial burden in the lungs and inhibited the level of COX-2. After faecal transplantation, cyclooxygenase 2 (COX-2) expression was restored and the inflammatory lesion in the lungs was reduced. Further research found that the deficiency of COX-2 inhibited endoplasmic reticulum stress (ER stress). This mechanism was completed by COX-2 interaction with BIP. Moreover, we found a positive feedback mechanism by which blocking ER stress could reduce COX-2 levels by the NF-κB pathway. Taken together, we reveal for the first time gut dysbacteriosis exacerbates M. bovis disease by limiting the COX-2/ER stress pathway. The finding strengthens the foundation of gut microbiota-targeted therapy for tuberculosis treatment.}, }
@article {pmid35765243, year = {2022}, author = {Hu, LP and Huang, W and Wang, X and Xu, C and Qin, WT and Li, D and Tian, G and Li, Q and Zhou, Y and Chen, S and Nie, HZ and Hao, Y and Song, J and Zhang, XL and Sundquist, J and Sundquist, K and Li, J and Jiang, SH and Zhang, ZG and Ji, J}, title = {Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {30}, number = {10}, pages = {3284-3299}, pmid = {35765243}, issn = {1525-0024}, mesh = {Animals ; Antifungal Agents ; *Colorectal Neoplasms/drug therapy/pathology ; Deoxyribonucleotides ; Dysbiosis ; Glucosephosphate Dehydrogenase ; Mice ; NADP ; *Terbinafine/pharmacology ; }, abstract = {Existing evidence indicates that gut fungal dysbiosis might play a key role in the pathogenesis of colorectal cancer (CRC). We sought to explore whether reversing the fungal dysbiosis by terbinafine, an approved antifungal drug, might inhibit the development of CRC. A population-based study from Sweden identified a total of 185 patients who received terbinafine after their CRC diagnosis and found that they had a decreased risk of death (hazard ratio = 0.50) and metastasis (hazard ratio = 0.44) compared with patients without terbinafine administration. In multiple mouse models of CRC, administration of terbinafine decreased the fungal load, the fungus-induced myeloid-derived suppressor cell (MDSC) expansion, and the tumor burden. Fecal microbiota transplantation from mice without terbinafine treatment reversed MDSC infiltration and partially restored tumor proliferation. Mechanistically, terbinafine directly impaired tumor cell proliferation by reducing the ratio of nicotinamide adenine dinucleotide phosphate (NADP[+]) to reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), suppressing the activity of glucose-6-phosphate dehydrogenase (G6PD), resulting in nucleotide synthesis disruption, deoxyribonucleotide (dNTP) starvation, and cell-cycle arrest. Collectively, terbinafine can inhibit CRC by reversing fungal dysbiosis, suppressing tumor cell proliferation, inhibiting fungus-induced MDSC infiltration, and restoring antitumor immune response.}, }
@article {pmid35764988, year = {2022}, author = {Ma, P and Mo, R and Liao, H and Qiu, C and Wu, G and Yang, C and Zhang, Y and Zhao, Y and Song, XJ}, title = {Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice.}, journal = {Journal of neuroinflammation}, volume = {19}, number = {1}, pages = {169}, pmid = {35764988}, issn = {1742-2094}, support = {KQTD20200820113040070//Science, Technology and Innovation Commission of Shenzhen Municipality/ ; JCYJ20200109141433384//The Foundation of Shenzhen Science and Technology Innovation Committee/ ; 7191001//Natural Science Foundation of Beijing Municipality/ ; NFSC81971062//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use/toxicity ; *Chronic Pain ; *Diabetes Mellitus ; *Gastrointestinal Microbiome ; Hyperalgesia/drug therapy/etiology ; Mice ; *Neuralgia/drug therapy/therapy ; Rats ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: Gut microbiota has been found involved in neuronal functions and neurological disorders. Whether and how gut microbiota impacts chronic somatic pain disorders remain elusive.<br><br>METHODS: Neuropathic pain was produced by different forms of injury or diseases, the chronic constriction injury (CCI) of the sciatic nerves, oxaliplatin (OXA) chemotherapy, and streptozocin (STZ)-induced diabetes in mice. Continuous feeding of antibiotics (ABX) cocktail was used to cause major depletion of the gut microbiota. Fecal microbiota, biochemical changes in the spinal cord and dorsal root ganglion (DRG), and the behaviorally expressed painful syndromes were assessed.<br><br>RESULTS: Under condition of gut microbiota depletion, CCI, OXA, or STZ treatment-induced thermal hyperalgesia or mechanical allodynia were prevented or completely suppressed. Gut microbiota depletion also prevented CCI or STZ treatment-induced glial cell activation in the spinal cord and inhibited cytokine production in DRG in OXA model. Interestingly, STZ treatment failed to induce the diabetic high blood glucose and painful hypersensitivity in animals with the gut microbiota depletion. ABX feeding starting simultaneously with CCI, OXA, or STZ treatment resulted in instant analgesia in all the animals. ABX feeding starting after establishment of the neuropathic pain in CCI- and STZ-, but not OXA-treated animals produced significant alleviation of the thermal hyeralgesia or mechanical allodynia. Transplantation of fecal bacteria from SPF mice to ABX-treated mice partially restored the gut microbiota and fully rescued the behaviorally expressed neuropathic pain, of which, Akkermansia, Bacteroides, and Desulfovibrionaceae phylus may play a key role.<br><br>CONCLUSION: This study demonstrates distinct roles of gut microbiota in the pathogenesis of chronic painful conditions with nerve injury, chemotherapy and diabetic neuropathy and supports the clinical significance of fecal bacteria transplantation.}, }
@article {pmid35763604, year = {2022}, author = {Rakotonirina, A and Galperine, T and Allémann, E}, title = {Fecal microbiota transplantation: a review on current formulations in Clostridioides difficile infection and future outlooks.}, journal = {Expert opinion on biological therapy}, volume = {22}, number = {7}, pages = {929-944}, doi = {10.1080/14712598.2022.2095901}, pmid = {35763604}, issn = {1744-7682}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Dysbiosis ; Fecal Microbiota Transplantation/adverse effects/methods ; *Gastrointestinal Microbiome ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {INTRODUCTION: The role of the gut microbiota in health and the pathogenesis of several diseases has been highlighted in recent years. Even though the precise mechanisms involving the microbiome in these ailments are still unclear, microbiota-modulating therapies have been developed. Fecal microbiota transplantation (FMT) has shown significant results against Clostridioides difficile infection (CDI), and its potential has been investigated for other diseases. Unfortunately, the technical aspects of the treatment make it difficult to implement. Pharmaceutical technology approaches to encapsulate microorganisms could play an important role in providing this treatment and render the treatment modalities easier to handle.<br><br>AREAS COVERED: After an overview of CDI, this narrative review aims to discuss the current formulations for FMT and specifically addresses the technical aspects of the treatment. This review also distinguishes itself by focusing on the hurdles and emphasizing the possible improvements using pharmaceutical technologies.<br><br>EXPERT OPINION: FMT is an efficient treatment for recurrent CDI. However, its standardization is overlooked. The approach of industrial and hospital preparations of FMT are different, but both show promise in their respective methodologies. Novel FMT formulations could enable further research on dysbiotic diseases in the future.}, }
@article {pmid35762770, year = {2022}, author = {Ma, L and Shen, Q and Lyu, W and Lv, L and Wang, W and Yu, M and Yang, H and Tao, S and Xiao, Y}, title = {Clostridium butyricum and Its Derived Extracellular Vesicles Modulate Gut Homeostasis and Ameliorate Acute Experimental Colitis.}, journal = {Microbiology spectrum}, volume = {10}, number = {4}, pages = {e0136822}, pmid = {35762770}, issn = {2165-0497}, mesh = {Animals ; *Clostridium butyricum/physiology ; *Colitis/chemically induced/microbiology/therapy ; Colon ; Dextran Sulfate/toxicity ; Disease Models, Animal ; *Extracellular Vesicles ; Homeostasis ; *Inflammatory Bowel Diseases ; Mice ; }, abstract = {Microbiological treatments are expected to have a role in the future management of inflammatory bowel disease (IBD). Clostridium butyricum (C. butyricum) is a probiotic microorganism that exhibits beneficial effects on various disease conditions. Although many studies have revealed that C. butyricum provides protective effects in mice with colitis, the way C. butyricum establishes beneficial results in the host remains unclear. In this study, we investigated the mechanisms by which C. butyricum modifies the gut microbiota, produces bacterial metabolites that may be involved, and, specifically, how microbial extracellular vesicles (EVs) positively influence IBD, using a dextran sulfate sodium (DSS)-induced colitis murine model in mice. First, we showed that C. butyricum provides a protective effect against colitis, as evidenced by the prevention of body weight loss, a reduction in the disease activity index (DAI) score, a shortened colon length, decreased histology score, and an improved gut barrier function, accompanied by reduced levels of pathogenic bacteria, including Escherichia/Shigella, and an increased relative abundance of butyrate-producing Clostridium sensu stricto-1 and Butyricicoccus. Second, we also confirmed that the gut microbiota and metabolites produced by C. butyricum played key roles in the attenuation of DSS-induced experimental colitis, as supported by the profound alleviation of colitis effects following fecal transplantation or fecal filtrate insertion supplied from C. butyricum-treated mice. Finally, C. butyricum-derived EVs protected the gut barrier function, improved gut microbiota homeostasis in ulcerative colitis, and contributed to overall colitis alleviation. IMPORTANCE This study indicated that C. butyricum provided a prevention effect against colitis mice, which involved protection of the intestinal barrier and positively regulating gut microbiota. Furthermore, we confirmed that the gut microbiota and metabolites that were induced by C. butyricum also contributed to the attenuation of DSS-induced colitis. Importantly, C. butyricum-derived EVs showed an effective impact in alleviating colitis.}, }
@article {pmid35761415, year = {2022}, author = {Liu, Y and Yang, M and Tang, L and Wang, F and Huang, S and Liu, S and Lei, Y and Wang, S and Xie, Z and Wang, W and Zhao, X and Tang, B and Yang, S}, title = {TLR4 regulates RORγt[+] regulatory T-cell responses and susceptibility to colon inflammation through interaction with Akkermansia muciniphila.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {98}, pmid = {35761415}, issn = {2049-2618}, mesh = {*Akkermansia ; Animals ; *Colitis/immunology ; Colon ; Dextran Sulfate/adverse effects ; Inflammation ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; RNA, Ribosomal, 16S/genetics/metabolism ; *T-Lymphocytes, Regulatory/immunology ; *Toll-Like Receptor 4/genetics ; }, abstract = {BACKGROUND: Well-balanced interactions between gut microbiota and the immune system are essential to prevent chronic intestinal inflammation, as observed in inflammatory bowel diseases (IBD). Toll-like receptor 4 (TLR4) functions as a sensor mediating the crosstalk between the intestinal commensal microbiome and host immunity, but the influence of TLR4 on the shaping of intestinal microbiota and immune responses during colon inflammation remains poorly characterized. We investigated whether the different susceptibilities to colitis between wild-type (WT) and TLR4[-/-] mice were gut microbiota-dependent and aimed to identify the potential immunity modulation mechanism.<br><br>METHODS: We performed antibiotic depletion of the microbiota, cohousing experiments, and faecal microbiota transplantation (FMT) in WT and TLR4[-/-] mice to assess the influence of TLR4 on intestinal microbial ecology. 16S rRNA sequencing was performed to dissect microbial discrepancies, and dysbiosis-associated immune perturbation was investigated by flow cytometry. Akkermansia muciniphila (A. muciniphila)-mediated immune modulation was confirmed through the T-cell transfer colitis model and bone marrow chimaera construction.<br><br>RESULTS: TLR4[-/-] mice experienced enhanced susceptibility to DSS-induced colitis. 16S rRNA sequencing showed notable discrepancy in the gut microbiota between WT and TLR4[-/-] mice. In particular, A. muciniphila contributed most to distinguishing the two groups. The T-cell transfer colitis model and bone marrow transplantation (BMT) consistently demonstrated that A. muciniphila ameliorated colitis by upregulating ROR&#x3b3;t[+] Treg cell-mediated immune responses. Mucosal biopsies from human manifested parallel outcomes with colon tissue from WT mice, as evidenced by the positive correlation between TLR4 expression and intestinal A. muciniphila colonization during homeostasis.<br><br>CONCLUSIONS: Our results demonstrate a novel protective role of TLR4 against intestinal inflammation, wherein it can modulate A. muciniphila-associated immune responses. These findings provide a new perspective on host-commensal symbiosis, which may be beneficial for developing potential therapeutic strategies. Video abstract.}, }
@article {pmid35760542, year = {2022}, author = {Hurych, J and Vejmelka, J and Hlinakova, L and Kramna, L and Larionov, V and Kulich, M and Cinek, O and Kohout, P}, title = {Protocol for faecal microbiota transplantation in irritable bowel syndrome: the MISCEAT study - a randomised, double-blind cross-over study using mixed microbiota from healthy donors.}, journal = {BMJ open}, volume = {12}, number = {6}, pages = {e056594}, pmid = {35760542}, issn = {2044-6055}, mesh = {Cross-Over Studies ; Diarrhea/therapy ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/methods ; Humans ; *Irritable Bowel Syndrome/therapy ; *Microbiota ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Several studies have demonstrated dysbiosis in irritable bowel syndrome (IBS). Therefore, faecal microbiota transplantation, whose effect and safety have been proven in Clostridioides difficile infections, may hold promise in other conditions, including IBS. Our study will examine the effectiveness of stool transfer with artificially increased microbial diversity in IBS treatment.<br><br>METHODS AND ANALYSIS: A three-group, double-blind,randomised, cross-over, placebo-controlled study of two pairs of gut microbiota transfer will be conducted in 99 patients with diarrhoeal or mixed type of IBS. Patients aged 18-65 will be randomised into three equally sized groups: group A will first receive two enemas of study microbiota mixture (deep-frozen stored stool microbiota mixed from eight healthy donors); after 8 weeks, they will receive two enemas with placebo (autoclaved microbiota mixture), whereas group B will first receive placebo, then microbiota mixture. Finally, group C will receive placebos only. The IBS Severity Symptom Score (IBS-SSS) questionnaires will be collected at baseline and then at weeks 3, 5, 8, 11, 13, 32. Faecal bacteriome will be profiled before and regularly after interventions using 16S rDNA next-generation sequencing. Food records, dietary questionnaires, anthropometry, bioimpedance, biochemistry and haematology workup will be obtained at study visits during the follow-up period. The primary outcome is the change in the IBS-SSS between the baseline and 4 weeks after the intervention for each patient compared with placebo. Secondary outcomes are IBS-SSS at 2 weeks after the intervention and 32 weeks compared with placebo and changes in the number of loose stools, Bristol stool scale, abdominal pain and bloating, anthropometric parameters, psychological evaluation and the gut microbiome composition.<br><br>ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Thomayer University Hospital, Czechia (G-18-26); study results will be published in peer-reviewed journals and presented at international conferences and patient group meetings.<br><br>TRIAL REGISTRATION NUMBER: NCT04899869.}, }
@article {pmid35759806, year = {2022}, author = {Li, Z and Ke, H and Lin, Q and Shen, Z and Chen, Y}, title = {Global trends in gut microbiota and clostridioides difficile infection research: A visualized study.}, journal = {Journal of infection and public health}, volume = {15}, number = {7}, pages = {806-815}, doi = {10.1016/j.jiph.2022.06.011}, pmid = {35759806}, issn = {1876-035X}, mesh = {*Clostridioides difficile ; *Clostridium Infections/epidemiology/microbiology ; *Cross Infection ; Dysbiosis ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {BACKGROUND: Clostridioides (clostridium) difficile infection (CDI) is the most common cause of nosocomial diarrheal disease, which has become a public health problem worldwide; gut dysbiosis plays a central role in its pathophysiology. This study conducted a bibliometric analysis of publications on gut microbiota and CDI to summarize the current status of research including research hotspots.<br><br>METHODS: Relevant publications from January 2004 to February 2022 were identified from the Web of Science Core Collection. Three bibliometric tools were used to perform visualization analyses.<br><br>RESULTS: A total of 1983 publications were analyzed. Annual publications increased from 11 in 2004-237 in 2021, with the US being the leading producer (47.55 % of all papers). EG Pamer had the highest average citations per article (average citations per item = 153.03, H-index = 29). Frontiers in Microbiology published the most papers. The main research foci were "fecal microbiota transplantation," "colonization resistance," and "multidrug-resistant bacteria." The keywords with the highest frequency in recent years include: gut dysbiosis, antibiotic resistance, bile-acids, 16&#xa0;s sequencing, multidrug-resistant bacteria, and short chain fatty acids.<br><br>CONCLUSIONS: Gut microbiota and CDI is likely to remain a prominent area of research in the foreseeable future. Current research hotspots ("fecal microbiota transplantation," "colonization resistance," and "multidrug-resistant bacteria") should receive even more attention in future studies.}, }
@article {pmid35759388, year = {2022}, author = {Jiang, L and Hong, Y and Xiao, P and Wang, X and Zhang, J and Liu, E and Li, H and Cai, Z}, title = {The Role of Fecal Microbiota in Liver Toxicity Induced by Perfluorooctane Sulfonate in Male and Female Mice.}, journal = {Environmental health perspectives}, volume = {130}, number = {6}, pages = {67009}, pmid = {35759388}, issn = {1552-9924}, mesh = {Alkanesulfonic Acids ; Animals ; Anti-Bacterial Agents ; Arginine ; Bacteria ; *Chemical and Drug Induced Liver Injury, Chronic ; Feces ; Female ; Fluorocarbons ; Male ; Mice ; *Microbiota ; }, abstract = {BACKGROUND: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that can cause hepatotoxicity. The underlying toxicological mechanism remains to be investigated. Given the critical role of fecal microbiota in liver function, it is possible that fecal microbiota may contribute to the liver toxicity induced by PFOS.<br><br>OBJECTIVES: We aimed to investigate the role of liver-fecal microbiota axis in modulating PFOS-induced liver injury in mice.<br><br>METHODS: Male and female mice were exposed to PFOS or vehicle for 14 d. In this investigation, 16S rDNA sequencing and metabolomic profiling were performed to identify the perturbed fecal microbiota and altered metabolites with PFOS exposure. In addition, antibiotic treatment, fecal microbiota transplantation, and bacterial administration were conducted to validate the causal role of fecal microbiota in mediating PFOS-induced liver injury and explore the potential underlying mechanisms.<br><br>RESULTS: Both male and female mice exposed to PFOS exhibited liver inflammation and steatosis, which were accompanied by fecal microbiota dysbiosis and the disturbance of amino acid metabolism in comparison with control groups. The hepatic lesions were fecal microbiota-dependent, as supported by antibiotic treatment and fecal microbiota transplantation. Mice with altered fecal microbiota in antibiotic treatment or fecal microbiota transplantation experiments exhibited altered arginine concentrations in the liver and feces. Notably, we observed sex-specific lower levels of key microbiota, including Lactobacillus, Enterococcus, and Akkermansia. Mice treated with specific bacteria showed lower arginine levels and lower expression of the phosphorylated mTOR and P70S6K, suggesting lower activity of the related pathway and mitigation of the pathological differences observed in PFOS-exposed mice.<br><br>CONCLUSIONS: Our study demonstrated the critical role of the fecal microbiota in PFOS-induced liver injury in mice. We also identified several critical bacteria that could protect against liver injury induced by PFOS in male and female mice. Our present research provided novel insights into the mechanism of PFOS-induced liver injury in mice. https://doi.org/10.1289/EHP10281.}, }
@article {pmid35759305, year = {2022}, author = {Davis, BT and Chen, Z and Islam, MBAR and Timken, ME and Procissi, D and Schwulst, SJ}, title = {Fecal Microbiota Transfer Attenuates Gut Dysbiosis and Functional Deficits After Traumatic Brain Injury.}, journal = {Shock (Augusta, Ga.)}, volume = {57}, number = {6}, pages = {251-259}, pmid = {35759305}, issn = {1540-0514}, support = {R01 GM130662/GM/NIGMS NIH HHS/United States ; R01 NS127865/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Brain Injuries, Traumatic/pathology ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Humans ; Mice ; *Neurodegenerative Diseases ; }, abstract = {BACKGROUND: Traumatic brain injury (TBI) is an underrecognized public health threat. Survivors of TBI often suffer long-term neurocognitive deficits leading to the progressive onset of neurodegenerative disease. Recent data suggests that the gut-brain axis is complicit in this process. However, no study has specifically addressed whether fecal microbiota transfer (FMT) attenuates neurologic deficits after TBI.<br><br>HYPOTHESIS: We hypothesized that fecal microbiota transfer would attenuate neurocognitive, anatomic, and pathologic deficits after TBI.<br><br>METHODS: C57Bl/6 mice were subjected to severe TBI (n&#x200a;=&#x200a;20) or sham-injury (n&#x200a;=&#x200a;20) via an open-head controlled cortical impact. Post-injury, this cohort of mice underwent weekly oral gavage with a slurry of healthy mouse stool or vehicle alone beginning 1&#x200a;h post-TBI followed by behavioral testing and neuropathologic analysis. 16S ribosomal RNA sequencing of fecal samples was performed to characterize gut microbial community structure pre- and post-injury. Zero maze and open field testing were used to evaluate post-traumatic anxiety, exploratory behavior, and generalized activity. 3D, contrast enhanced, magnetic resonance imaging was used to determine differences in cortical volume loss and white matter connectivity. Prior to euthanasia, brains were harvested for neuropathologic analysis.<br><br>RESULTS: Fecal microbiome analysis revealed a large variance between TBI, and sham animals treated with vehicle, while FMT treated TBI mice had restoration of gut dysbiosis back to levels of control mice. Neurocognitive testing demonstrated a rescue of normal anxiety-like and exploratory behavior in TBI mice treated with FMT. FMT treated TBI mice spent a greater percentage of time (22%, P&#x200a;=&#x200a;0.0001) in the center regions of the Open Field as compared to vehicle treated TBI mice (13%). Vehicle-treated TBI animals also spent less time (19%) in the open areas of zero maze than FMT treated TBI mice (30%, P&#x200a;=&#x200a;0.0001). Comparing in TBI mice treated with FMT, MRI demonstrated a marked attenuation in ventriculomegaly (P&#x200a;<&#x200a;0.002) and a significant change in fractional anisotropy (i.e., loss of white matter connectivity) (P&#x200a;<&#x200a;0.0001). Histologic analysis of brain sections revealed a FMT- injury dependent interaction in the microglia/macrophage-specific ionized calcium-binding protein, Iba1 (P&#x200a;=&#x200a;0.002).<br><br>CONCLUSION: These data suggest that restoring a pre-injury gut microbial community structure may be a promising therapeutic intervention after TBI.}, }
@article {pmid35756645, year = {2022}, author = {Chen, M and Liu, M and Li, C and Peng, S and Li, Y and Xu, X and Sun, M and Sun, X}, title = {Fecal Microbiota Transplantation Effectively Cures a Patient With Severe Bleeding Immune Checkpoint Inhibitor-Associated Colitis and a Short Review.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {913217}, pmid = {35756645}, issn = {2234-943X}, abstract = {Immune checkpoint inhibitors (ICIs) have opened up a new way for tumor therapy but simultaneously led to the occurrence of immune-related adverse events. We report a case of successful treatment of PD-1 inhibitor-associated colitis with fecal microbiota transplantation (FMT). The patient was a palatal malignant melanoma who developed diarrhea and hematochezia accompanied by fever, gastrointestinal bleeding, and infection after the third treatment with PD-1 (Toripalimab). The patient received general treatment unsuccessful, corticosteroid therapy after initial success but rapid loss of response, and finally successful treatment after fecal microbiota transplantation.}, }
@article {pmid35755849, year = {2022}, author = {Aira, A and Rubio, E and Ruiz, A and Vergara, A and Casals-Pascual, C and Rico, V and Suñé-Negre, JM and Soriano, A}, title = {New Procedure to Maintain Fecal Microbiota in a Dry Matrix Ready to Encapsulate.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {899257}, pmid = {35755849}, issn = {2235-2988}, mesh = {*Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is one of the recommended treatments for recurrent Clostridioides difficile infection, but endoscopy and available oral formulations still have several limitations in their preparation, storage, and administration. The need for a viable oral formulation that facilitates the implementation of this highly effective therapy in different settings has led us to test the microcrystalline cellulose particles as an adsorbent of concentrated filtered fresh feces in comparison to lyophilized feces. This free-flowing material can provide protection to bacteria and results in a dried product able to maintain the viability of the microbiota for a long time. Adsorbate formulation showed a stabilizing effect in gut microbiota, maintaining bacteria viability and preserving its diversity, and is a competitive option for lyophilized capsules.}, }
@article {pmid35753948, year = {2022}, author = {Maida, M and Annibale, B and Benedetti, A and Burra, P and Frulloni, L and Ianiro, G and Luzza, F and Repici, A and Savarino, E and Sinagra, E and Vecchi, M and Ricciardiello, L and , }, title = {Quality of endoscopic screening for colorectal cancer in Italy: A national survey.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {54}, number = {10}, pages = {1410-1418}, doi = {10.1016/j.dld.2022.06.002}, pmid = {35753948}, issn = {1878-3562}, mesh = {Cecum ; *Colonoscopy ; *Colorectal Neoplasms/diagnosis/epidemiology ; Early Detection of Cancer ; Humans ; Italy/epidemiology ; Mass Screening ; Occult Blood ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) is a major healthcare problem all over the world and screening is effective in reducing mortality and increasing survival. Since colonoscopy has a central role in faecal immunochemical test (FIT)-based CRC screening and surveillance, consistent quality measures are essential to ensure quality and outcomes. Nevertheless, screening modalities in clinical practice may differ according to the centers experience and the local availability of instrumentation and devices.<br><br>AIMS: to assess the quality of endoscopic screening for CRC and adherence to international guidelines across Gastroenterology Departments in Italy.<br><br>METHODS: All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey.<br><br>RESULTS: Data from 64 hospitals from 17 Italian regions were analyzed. 32/64 (50.0%) were from northern, 12/64 (18.75%) from central and 20/64 (31.25%) from southern Italy. Each center is equipped with a median of 5.0 (3.5-7.0) endoscopists involved in CRC screening, 71.4% of which are gastroenterologists. After a positive FIT, most centers (93.8%) schedule a colonoscopy within 3 months. High-definition video endoscopy is routinely performed in 68.8% and chromoendoscopy in 53.1% of centers. Withdrawal time is &#x2265;6&#xa0;min in 79.9% and cecal intubation rate is &#x2265;90% in 94.4% of departments. Finally, in 92.7% of centers adenoma detection rate (ADR) overcome the minimum standard of 25%. Analyzing the data by regional areas, a significant higher number of median endoscopic examinations/year (6500 vs 4000 and 3000, respectively, p&#xa0;=&#xa0;0.024) and of endoscopists per center (6.5 vs 5.0 and 3.5, respectively, p&#xa0;<&#xa0;0.001) has been registered in the northern compared to central-southern centers.<br><br>CONCLUSIONS: Data from this survey show adequacy and good quality of endoscopic screening for CRC in Italy, highlighting, at the same time, relevant deficiencies and a discrepancy in procedural attitudes between the different centers. These findings call for a urgent action to overcome the shortcomings, refine and homogenize the behaviour of all screening centers in the national territory and improve the outcomes.}, }
@article {pmid35753395, year = {2022}, author = {Li, X and Xiao, F and Li, Y and Hu, H and Xiao, Y and Xu, Q and Li, D and Yu, G and Wang, Y and Zhang, T}, title = {Characteristics and management of children with Clostridioides difficile infection at a tertiary pediatric hospital in China.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {26}, number = {4}, pages = {102380}, pmid = {35753395}, issn = {1678-4391}, mesh = {Abdominal Pain/chemically induced/drug therapy ; Anti-Bacterial Agents/therapeutic use ; Child ; Child, Preschool ; China ; *Clostridioides difficile ; *Clostridium Infections/drug therapy ; Diarrhea/chemically induced/drug therapy ; Female ; Gastrointestinal Hemorrhage/chemically induced ; Hospitals, Pediatric ; Humans ; Male ; Metronidazole/therapeutic use ; Recurrence ; Retrospective Studies ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Clostridiodes difficile infection (CDI) is one of the most common causes of antibiotic-associated diarrhea in children. Conventional antibiotics and emerging fecal microbiota transplantation (FMT) are used to treat CDI.<br><br>METHODS: Children with CDI admitted to the Shanghai Children's Hospital, from September 2014 to September 2020, were retrospectively included to this observational study. Pediatric patients were assigned as initial CDI and recurrent CDI (RCDI), and symptoms, comorbidities, imaging findings, laboratory tests, and treatments were systematically recorded and analyzed.<br><br>RESULTS: Of 109 pediatric patients with CDI, 58 were boys (53.2%), and the median age was 5 years (range, 2-9 years). The main clinical symptoms of CDI children were diarrhea (109/109, 100%), hematochezia (55/109, 50.46%), abdominal pain (40/109, 36.70%); fever, pseudomembrane, vomit, and bloating were observed in 39 (35.78%), 33 (30.28%), and 24 (22.02%) patients, respectively. For the primary therapy with conventional antibiotics, 68 patients received metronidazole, and 41 patients received vancomycin. RCDI occurred in 48.53% (33/68) of those initially treated with metronidazole compared with 46.33% (19/41) of those initially treated with vancomycin (p=0.825). The total resolution rate of FMT for RCDI children was significantly higher than with vancomycin treatment (28/29, 96.55% vs 11/23, 47.83%, p < 0.001). There were no serious adverse events (SAEs) reported after two months of FMT.<br><br>CONCLUSIONS: The major manifestations of children with CDI were diarrhea, hematochezia, and abdominal pain. The cure rate of FMT for pediatric RCDI is superior to vancomycin treatment.}, }
@article {pmid35753153, year = {2022}, author = {Cao, Z and Sugimura, N and Burgermeister, E and Ebert, MP and Zuo, T and Lan, P}, title = {The gut virome: A new microbiome component in health and disease.}, journal = {EBioMedicine}, volume = {81}, number = {}, pages = {104113}, pmid = {35753153}, issn = {2352-3964}, mesh = {Animals ; Bacteria ; *Bacteriophages ; Humans ; Mammals ; *Microbiota ; Virome ; *Viruses ; }, abstract = {The human gastrointestinal tract harbours an abundance of viruses, collectively known as the gut virome. The gut virome is highly heterogeneous across populations and is linked to geography, ethnicity, diet, lifestyle, and urbanisation. The currently known function of the gut virome varies greatly across human populations, and much remains unknown. We review current literature on the human gut virome, and the intricate trans-kingdom interplay among gut viruses, bacteria, and the mammalian host underlying health and diseases. We summarise evidence on the use of the gut virome as diagnostic markers and a therapeutic target. We shed light on novel avenues of microbiome-inspired diagnosis and therapies. We also review pre-clinical and clinical studies on gut virome-rectification-based therapies, including faecal microbiota transplantation, faecal virome transplantation, and refined phage therapy. Our review suggests that future research effort should focus on unravelling the mechanisms exerted by gut viruses/phages in human pathophysiology, and on developing phage-prompted precision therapies.}, }
@article {pmid35752523, year = {2022}, author = {Gamé, X and Ruffion, A and Cornu, JN and Phé, V and Peyronnet, B and Perrouin-Verbe, MA and Aublant, C and Adé, A and Chartier-Kastler, E}, title = {Sacral neuromodulation: Rechargeable versus non-rechargeable device. What would the patient preferences be in France?.}, journal = {Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie}, volume = {32}, number = {10}, pages = {672-680}, doi = {10.1016/j.purol.2022.04.011}, pmid = {35752523}, issn = {1166-7087}, mesh = {Cross-Sectional Studies ; *Electric Stimulation Therapy ; *Fecal Incontinence ; Female ; Humans ; Male ; Middle Aged ; Patient Preference ; Sacrum ; Treatment Outcome ; *Urinary Bladder, Overactive ; *Urinary Retention ; }, abstract = {AIMS: Sacral neuromodulation (SNM) is a minimally invasive technique that provides effective treatment for the management of refractory overactive bladder (OAB), non-obstructive urinary retention (NOUR), and fecal incontinence (FI). This study assessed patient preferences between the currently available non-rechargeable SNM device and a new, full-body magnetic resonance imaging (MRI)-safe, smaller, rechargeable device.<br><br>METHODS: An online cross-sectional survey was conducted among French OAB, NOUR, FI patients, recruited via a market research vendor. To assess their preferences, patients were asked to indicate their level of agreement with 10 statements regarding the size of the device, its rechargeability, and the role of MRI using a 6-item Likert scale. A descriptive statistical analysis was performed.<br><br>RESULTS: In all, 95 patients (68% women), mean age 50 years, were included in the study: 51% were treated for OAB; 44% received an oral treatment and 28% had SNM. Overall, 71% of the 95&#xa0;patients indicated a preference for the new device; 75% considered that recharging the device would not impact their lifestyle; 74% believed that the smaller size of the rechargeable device would facilitate their choice to be treated with SNM; 80% found full-body MRI compatibility important.<br><br>CONCLUSIONS: Most patients may prefer the new rechargeable SNM device over the current "standard". Compatibility with full-body MRI and the smaller device size seemed the key features of the newer device that would influence their choice of being treated with SNM. Future national and international recommendations should consider a shared decision-making process between the physician and the patient.}, }
@article {pmid35751882, year = {2022}, author = {Liu, T and Li, YL and Zhou, LJ and Sun, XN and Wang, YL and Du, LJ and Liu, Y and Zhu, H and Chen, BY and Sun, JY and Liu, Y and Xu, S and Ye, HL and Huang, SJ and Wang, X and Li, B and Duan, SZ}, title = {Mineralocorticoid receptor deficiency in Treg cells ameliorates DSS-induced colitis in a gut microbiota-dependent manner.}, journal = {Immunology}, volume = {167}, number = {1}, pages = {94-104}, doi = {10.1111/imm.13522}, pmid = {35751882}, issn = {1365-2567}, mesh = {Animals ; *Colitis/chemically induced/therapy ; Colon ; Dextran Sulfate ; Disease Models, Animal ; Forkhead Transcription Factors/genetics ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Receptors, Mineralocorticoid/genetics ; T-Lymphocytes, Regulatory ; }, abstract = {Mineralocorticoid receptor (MR) is a classic nuclear receptor and an effective drug target in the cardiovascular system. The function of MR in immune cells such as macrophages and T cells has been increasingly appreciated. The aim of this study was to investigate the function of Treg MR in the process of inflammatory bowel disease (IBD). We treated Treg MR-deficient (MR[flox/flox] Foxp3[YFP-Cre] , KO) mice and control (Foxp3[YFP-Cre] , WT) mice with dextran sodium sulphate (DSS) to induce colitis and found that the severity of DSS-induced colitis was markedly alleviated in Treg MR-deficient mice, accompanied by reduced production of inflammatory cytokines, and relieved infiltration of monocytes, neutrophils and interferon γ[+] T cells in colon lamina propria. Faecal microbiota of mice with colitis was analysed by 16S rRNA gene sequencing and the composition of gut microbiota was vastly changed in Treg MR-deficient mice. Furthermore, depletion of gut microbiota by antibiotics abolished the protective effects of Treg MR deficiency and resulted in similar severity of DSS-induced colitis in WT and KO mice. Faecal microbiota transplantation from KO mice attenuated DSS-induced colitis characterized by alleviated inflammatory infiltration compared to that from WT mice. Hence, our study demonstrates that Treg MR deficiency protects against DSS-induced colitis by attenuation of colonic inflammatory infiltration. Gut microbiota is both sufficient and necessary for Treg MR deficiency to exert the beneficial effects.}, }
@article {pmid35748886, year = {2022}, author = {Ching, CK and Nobel, YR and Pereira, MR and Verna, EC}, title = {The role of gastrointestinal pathogen polymerase chain reaction testing in liver transplant recipients hospitalized with diarrhea.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {24}, number = {4}, pages = {e13873}, doi = {10.1111/tid.13873}, pmid = {35748886}, issn = {1399-3062}, mesh = {*Clostridioides difficile/genetics ; Diarrhea/diagnosis ; Escherichia coli ; Feces ; Hospitalization ; Humans ; *Liver Transplantation/adverse effects ; Multiplex Polymerase Chain Reaction ; Transplant Recipients ; }, abstract = {BACKGROUND: Diarrhea is a common symptom among liver transplant (LT) recipients and can result in significant morbidity. The utility of PCR-based multiplex gastrointestinal (GI) pathogen panels in this population is unknown.<br><br>METHODS: We assessed incidence, predictors, and outcomes of GI PCR positivity among inpatients who underwent stool pathogen testing with the FilmArray multiplex GI PCR panel at our institution within 1 year following LT from April 2015 to December 2019.<br><br>RESULTS: A total of 112 patients were identified. Of these, 14 (12.5%) had a positive PCR for any pathogen. Escherichia coli (n&#xa0;=&#xa0;9) and Norovirus (n&#xa0;=&#xa0;5) were the most common pathogens detected. Recipients with a positive PCR were significantly further from LT (median 74.5&#xa0;vs. 15.5 days, p&#xa0;<&#xa0;.01) and tested earlier during hospitalization (median 1.0&#xa0;vs. 9.0 days, p&#xa0;<&#xa0;.01). C. difficile was positive in 20.0% of patients with a positive PCR and 11.4% with a negative PCR. CMV viremia was observed in 11.6% of patients, all in the negative PCR group. Following a positive PCR, patients were more likely to have a change in antimicrobial regimen (71.4%&#xa0;vs. 28.6%, p&#xa0;=&#xa0;.02), a shorter length of stay (median 7.5&#xa0;vs. 17.5 days, p&#xa0;<&#xa0;.01), and a trend toward lower rates of readmission and colonoscopy within 30&#xa0;days.<br><br>CONCLUSIONS: In hospitalized LT recipients with diarrhea, GI PCR pathogen identification was associated with the use of targeted antimicrobial therapy and a shorter length of stay. GI PCR testing should be considered early during admission and later in the post-LT period.}, }
@article {pmid35748460, year = {2023}, author = {Catalán-Serra, I and Ricanek, P and Grimstad, T}, title = {"Out of the box" new therapeutic strategies for Crohn´s disease: moving beyond biologics.}, journal = {Revista espanola de enfermedades digestivas}, volume = {115}, number = {11}, pages = {614-634}, doi = {10.17235/reed.2022.9010/2022}, pmid = {35748460}, issn = {1130-0108}, mesh = {Humans ; *Biological Products/therapeutic use ; *Crohn Disease/therapy ; Quality of Life ; Inflammation ; Enteral Nutrition ; }, abstract = {New treatment options beyond immunosuppression have emerged in recent years for patients with Crohn´s disease (CD), a chronic systemic condition affecting primarily the gut with great impact in the quality of life. The cause of CD is largely unknown, and a curative treatment is not yet available. In addition, despite the growing therapeutic armamentarium in recent years almost half of the patients don´t achieve a sustained response over time. Thus, new therapeutic strategies are urgently needed. In this review, we discuss the current state of promising new "out of the box" possibilities to control chronic inflammation beyond current pharmacological treatments, including: exclusive enteral nutrition, specific diets, cell therapies using T regs, hyperbaric oxygen, fecal microbiota transplantation, phage therapy, helminths, cannabis and vagal nerve stimulation. The exploration of original and novel therapeutic modalities is key to address their potential as main or complementary treatments in selected CD populations in order to increase efficacy, minimize side effects and improve quality of life of patients.}, }
@article {pmid35745805, year = {2022}, author = {Yang, C and Sung, J and Long, D and Alghoul, Z and Merlin, D}, title = {Prevention of Ulcerative Colitis by Autologous Metabolite Transfer from Colitogenic Microbiota Treated with Lipid Nanoparticles Encapsulating an Anti-Inflammatory Drug Candidate.}, journal = {Pharmaceutics}, volume = {14}, number = {6}, pages = {}, pmid = {35745805}, issn = {1999-4923}, support = {I01 BX002526/BX/BLRD VA/United States ; R01 DK107739/DK/NIDDK NIH HHS/United States ; IK6 BX004476/BX/BLRD VA/United States ; BX002526//Atlanta VA Medical Center/ ; BX004476//Atlanta VA Medical Center/ ; R01 DK116306/DK/NIDDK NIH HHS/United States ; RO1-DK-107739/DK/NIDDK NIH HHS/United States ; 689659//Crohn's and Colitis Foundation/ ; RO1-DK-116306/DK/NIDDK NIH HHS/United States ; }, abstract = {Modulating the gut microbiota composition is a potent approach to treat various chronic diseases, including obesity, metabolic syndrome, and ulcerative colitis (UC). However, the current methods, such as fecal microbiota transplantation, carry a risk of serious infections due to the transmission of multi-drug-resistant organisms. Here, we developed an organism-free strategy in which the gut microbiota is modulated ex vivo and microbiota-secreted metabolites are transferred back to the host. Using feces collected from the interleukin-10 (IL-10) knockout mouse model of chronic UC, we found that a drug candidate (M13)-loaded natural-lipid nanoparticle (M13/nLNP) modified the composition of the ex vivo-cultured inflamed gut microbiota and its secreted metabolites. Principal coordinate analysis (PCoA) showed that M13/nLNP shifted the inflamed microbiota composition toward the non-inflamed direction. This compositional modification induced significant changes in the chemical profiles of secreted metabolites, which proved to be anti-inflammatory against in vitro-cultured NF-κβ reporter cells. Further, when these metabolites were orally administered to mice, they established strong protection against the formation of chronic inflammation. Our study demonstrates that ex vivo modulation of microbiota using M13/nLNP effectively reshaped the microbial secreted metabolites and that oral transfer of these metabolites might be an effective and safe therapeutic approach for preventing chronic UC.}, }
@article {pmid35745496, year = {2022}, author = {Alam, MJ and Xie, L and Yap, YA and Marques, FZ and Robert, R}, title = {Manipulating Microbiota to Treat Atopic Dermatitis: Functions and Therapies.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, pmid = {35745496}, issn = {2076-0817}, support = {105663/WT_/Wellcome Trust/United Kingdom ; //Senior Medical Research Fellowship from the Sylvia and Charles Viertel Charitable Foundation/ ; //Monash Graduate Scholarship from Monash University, Australia/ ; }, abstract = {Atopic dermatitis (AD) is a globally prevalent skin inflammation with a particular impact on children. Current therapies for AD are challenged by the limited armamentarium and the high heterogeneity of the disease. A novel promising therapeutic target for AD is the microbiota. Numerous studies have highlighted the involvement of the skin and gut microbiota in the pathogenesis of AD. The resident microbiota at these two epithelial tissues can modulate skin barrier functions and host immune responses, thus regulating AD progression. For example, the pathogenic roles of Staphylococcus aureus in the skin are well-established, making this bacterium an attractive target for AD treatment. Targeting the gut microbiota is another therapeutic strategy for AD. Multiple oral supplements with prebiotics, probiotics, postbiotics, and synbiotics have demonstrated promising efficacy in both AD prevention and treatment. In this review, we summarize the association of microbiota dysbiosis in both the skin and gut with AD, and the current knowledge of the functions of commensal microbiota in AD pathogenesis. Furthermore, we discuss the existing therapies in manipulating both the skin and gut commensal microbiota to prevent or treat AD. We also propose potential novel therapies based on the cutting-edge progress in this area.}, }
@article {pmid35745257, year = {2022}, author = {Bian, J and Liebert, A and Bicknell, B and Chen, XM and Huang, C and Pollock, CA}, title = {Faecal Microbiota Transplantation and Chronic Kidney Disease.}, journal = {Nutrients}, volume = {14}, number = {12}, pages = {}, pmid = {35745257}, issn = {2072-6643}, mesh = {*Clostridium Infections ; *Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation/methods ; Feces ; Humans ; Renal Dialysis ; *Renal Insufficiency, Chronic/therapy ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) has attracted increasing attention as an intervention in many clinical conditions, including autoimmune, enteroendocrine, gastroenterological, and neurological diseases. For years, FMT has been an effective second-line treatment for Clostridium difficile infection (CDI) with beneficial outcomes. FMT is also promising in improving bowel diseases, such as ulcerative colitis (UC). Pre-clinical and clinical studies suggest that this microbiota-based intervention may influence the development and progression of chronic kidney disease (CKD) via modifying a dysregulated gut-kidney axis. Despite the high morbidity and mortality due to CKD, there are limited options for treatment until end-stage kidney disease occurs, which results in death, dialysis, or kidney transplantation. This imposes a significant financial and health burden on the individual, their families and careers, and the health system. Recent studies have suggested that strategies to reverse gut dysbiosis using FMT are a promising therapy in CKD. This review summarises the preclinical and clinical evidence and postulates the potential therapeutic effect of FMT in the management of CKD.}, }
@article {pmid35739571, year = {2022}, author = {Münzker, J and Haase, N and Till, A and Sucher, R and Haange, SB and Nemetschke, L and Gnad, T and Jäger, E and Chen, J and Riede, SJ and Chakaroun, R and Massier, L and Kovacs, P and Ost, M and Rolle-Kampczyk, U and Jehmlich, N and Weiner, J and Heiker, JT and Klöting, N and Seeger, G and Morawski, M and Keitel, V and Pfeifer, A and von Bergen, M and Heeren, J and Krügel, U and Fenske, WK}, title = {Functional changes of the gastric bypass microbiota reactivate thermogenic adipose tissue and systemic glucose control via intestinal FXR-TGR5 crosstalk in diet-induced obesity.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {96}, pmid = {35739571}, issn = {2049-2618}, mesh = {Adipose Tissue/metabolism ; Animals ; Bile Acids and Salts ; Blood Glucose ; *Diabetes Mellitus, Type 2 ; Diet ; *Gastric Bypass ; *Microbiota ; Obesity/metabolism/surgery ; Rats ; Receptors, G-Protein-Coupled/genetics/metabolism ; Taurine ; Thermogenesis ; }, abstract = {BACKGROUND: Bariatric surgery remains the most effective therapy for adiposity reduction and remission of type 2 diabetes. Although different bariatric procedures associate with pronounced shifts in the gut microbiota, their functional role in the regulation of energetic and metabolic benefits achieved with the surgery are not clear.<br><br>METHODS: To evaluate the causal as well as the inherent therapeutic character of the surgery-altered gut microbiome in improved energy and metabolic control in diet-induced obesity, an antibiotic cocktail was used to eliminate the gut microbiota in diet-induced obese rats after gastric bypass surgery, and gastric bypass-shaped gut microbiota was transplanted into obese littermates. Thorough metabolic profiling was combined with omics technologies on samples collected from cecum and plasma to identify adaptions in gut microbiota-host signaling, which control improved energy balance and metabolic profile after surgery.<br><br>RESULTS: In this study, we first demonstrate that depletion of the gut microbiota largely reversed the beneficial effects of gastric bypass surgery on negative energy balance and improved glucolipid metabolism. Further, we show that the gastric bypass-shaped gut microbiota reduces adiposity in diet-induced obese recipients by re-activating energy expenditure from metabolic active brown adipose tissue. These beneficial effects were linked to improved glucose homeostasis, lipid control, and improved fatty liver disease. Mechanistically, these effects were triggered by modulation of taurine metabolism by the gastric bypass gut microbiota, fostering an increased abundance of intestinal and circulating taurine-conjugated bile acid species. In turn, these bile acids activated gut-restricted FXR and systemic TGR5 signaling to stimulate adaptive thermogenesis.<br><br>CONCLUSION: Our results establish the role of the gut microbiome in the weight loss and metabolic success of gastric bypass surgery. We here identify a signaling cascade that entails altered bile acid receptor signaling resulting from a collective, hitherto undescribed change in the metabolic activity of a cluster of bacteria, thereby readjusting energy imbalance and metabolic disease in the obese host. These findings strengthen the rationale for microbiota-targeted strategies to improve and refine current therapies of obesity and metabolic syndrome. Video Abstract Bariatric Surgery (i.e. RYGB) or the repeated fecal microbiota transfer (FMT) from RYGB donors into DIO (diet-induced obesity) animals induces shifts in the intestinal microbiome, an effect that can be impaired by oral application of antibiotics (ABx). Our current study shows that RYGB-dependent alterations in the intestinal microbiome result in an increase in the luminal and systemic pool of Taurine-conjugated Bile acids (TCBAs) by various cellular mechanisms acting in the intestine and the liver. TCBAs induce signaling via two different receptors, farnesoid X receptor (FXR, specifically in the intestines) and the G-protein-coupled bile acid receptor TGR5 (systemically), finally resulting in metabolic improvement and advanced weight management. BSH, bile salt hydrolase; BAT brown adipose tissue.}, }
@article {pmid35739196, year = {2022}, author = {Qiao, L and Zhang, X and Pi, S and Chang, J and Dou, X and Yan, S and Song, X and Chen, Y and Zeng, X and Zhu, L and Xu, C}, title = {Dietary supplementation with biogenic selenium nanoparticles alleviate oxidative stress-induced intestinal barrier dysfunction.}, journal = {NPJ science of food}, volume = {6}, number = {1}, pages = {30}, pmid = {35739196}, issn = {2396-8370}, support = {32072746//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Selenium (Se) is an essential micronutrient that promotes body health. Endemic Se deficiency is a major nutritional challenge worldwide. The low toxicity, high bioavailability, and unique properties of biogenic Se nanoparticles (SeNPs) allow them to be used as a therapeutic drug and Se nutritional supplement. This study was conducted to investigate the regulatory effects of dietary SeNPs supplementation on the oxidative stress-induced intestinal barrier dysfunction and its association with mitochondrial function and gut microbiota in mice. The effects of dietary SeNPs on intestinal barrier function and antioxidant capacity and its correlation with gut microbiota were further evaluated by a fecal microbiota transplantation experiment. The results showed that Se deficiency caused a redox imbalance, increased the levels of pro-inflammatory cytokines, altered the composition of the gut microbiota, and impaired mitochondrial structure and function, and intestinal barrier injury. Exogenous supplementation with biogenic SeNPs effectively alleviated diquat-induced intestinal barrier dysfunction by enhancing the antioxidant capacity, inhibiting the overproduction of reactive oxygen species (ROS), preventing the impairment of mitochondrial structure and function, regulating the immune response, maintaining intestinal microbiota homeostasis by regulating nuclear factor (erythroid-derived-2)-like 2 (Nrf2)-mediated NLR family pyrin domain containing 3 (NLRP3) signaling pathway. In addition, Se deficiency resulted in a gut microbiota phenotype that is more susceptible to diquat-induced intestinal barrier dysfunction. Supranutritional SeNPs intake can optimize the gut microbiota to protect against intestinal dysfunctions. This study demonstrates that dietary supplementation of SeNPs can prevent oxidative stress-induced intestinal barrier dysfunction through its regulation of mitochondria and gut microbiota.}, }
@article {pmid35739018, year = {2022}, author = {Carneiro, PV and Montenegro, NA and Lana, A and Amato, AA and Santos, GM}, title = {Lipids from gut microbiota: pursuing a personalized treatment.}, journal = {Trends in molecular medicine}, volume = {28}, number = {8}, pages = {631-643}, doi = {10.1016/j.molmed.2022.06.001}, pmid = {35739018}, issn = {1471-499X}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome/physiology ; Humans ; Lipids ; Precision Medicine ; }, abstract = {The discovery of microbiome metabolites has enlivened the field of fecal transplantation for therapeutic purposes. However, the transfer of pathogenic living organisms was recently observed to limit its therapeutic potential by increasing the risk of infection. Lipids produced by gut microbiota enter the circulation and control many phenotypic changes associated with microbiota composition. Fecal lipids significantly impact the regulation of several cell signaling pathways, including inflammation. Focusing on these molecules, we review how bioactive gut microbiota-associated lipids affect cellular functioning and clinical outcome. Here, we interrogate whether the gut microbiota can be considered a cutting-edge biotechnological tool for rapid metabolic engineering of meaningful lipids to offer a novel personalized therapy.}, }
@article {pmid35737457, year = {2022}, author = {Rei, D and Saha, S and Haddad, M and Rubio, AH and Perlaza, BL and Berard, M and Ungeheuer, MN and Sokol, H and Lledo, PM}, title = {Age-associated gut microbiota impair hippocampus-dependent memory in a vagus-dependent manner.}, journal = {JCI insight}, volume = {7}, number = {15}, pages = {}, pmid = {35737457}, issn = {2379-3708}, mesh = {Adult ; Aged ; Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Hippocampus/physiology ; Humans ; Mice ; Neurogenesis ; Vagus Nerve ; }, abstract = {Aging is known to be associated with hippocampus-dependent memory decline, but the underlying causes of this age-related memory impairment remain highly debated. Here, we show that fecal microbiota transplantation (FMT) from aged, but not young, animal donors into young mice is sufficient to trigger profound hippocampal alterations, including astrogliosis, decreased adult neurogenesis, decreased novelty-induced neuronal activation, and impairment in hippocampus-dependent memory. Furthermore, similar alterations were reported when mice were subjected to an FMT from aged human donors. To decipher the mechanisms involved in mediating these microbiota-induced effects on brain function, we mapped the vagus nerve-related (VN-related) neuronal activity patterns and report that aged FMT animals showed a reduction in neuronal activity in the ascending-VN output brain structure, whether under basal condition or after VN stimulation. Targeted pharmacogenetic manipulation of VN-ascending neurons demonstrated that the decrease in vagal activity is detrimental to hippocampal functions. In contrast, increasing vagal ascending activity alleviated the adverse effects of aged mouse FMT on hippocampal functions and had a promnesic effect in aged mice. Thus, pharmacogenetic VN stimulation is a potential therapeutic strategy to lessen microbiota-dependent age-associated impairments in hippocampal functions.}, }
@article {pmid35736494, year = {2022}, author = {Alghamdi, MA and Al-Ayadhi, L and Hassan, WM and Bhat, RS and Alonazi, MA and El-Ansary, A}, title = {Bee Pollen and Probiotics May Alter Brain Neuropeptide Levels in a Rodent Model of Autism Spectrum Disorders.}, journal = {Metabolites}, volume = {12}, number = {6}, pages = {}, pmid = {35736494}, issn = {2218-1989}, support = {(RSP-2021/237)//Researchers Supporting Project, King Saud University, Riyadh, Saudi Arabia/ ; }, abstract = {Neuropeptides play a major role in maintaining normal brain development in children. Dysfunction of some specific neuropeptides can lead to autism spectrum disorders (ASD) in terms of social interaction and repetitive behavior, but the exact underlying etiological mechanisms are still not clear. In this study, we used an animal model of autism to investigate the role of bee pollen and probiotic in maintaining neuropeptide levels in the brain. We measured the Alpha-melanocyte-stimulating hormone (α-MSH), Beta-endorphin (β-End), neurotensin (NT), and substance P (SP) in brain homogenates of six studied groups of rats. Group I served as control, given only PBS for 30 days; Group II as an autistic model treated with 250 mg PPA/kg BW/day for 3 days after being given PBS for 27 days. Groups III-VI were denoted as intervention groups. G-III was treated with bee pollen (BP) 250 mg/kg body weight/day; G-IV with Lactobacillus paracaseii (LB) (109 CFU/mL) suspended in PBS; G-V with 0.2 g/kg body weight/day Protexin[®], a mixture of probiotics (MPB); and G-VI was transplanted with stool from normal animals (FT) for 27 days prior to the induction of PPA neurotoxicity on the last 3 days of study (days 28-30). The obtained data were analyzed through the use of principal component analysis (PCA), discriminant analysis (DA), hierarchical clustering, and receiver operating characteristic (ROC) curves as excellent statistical tools in the field of biomarkers. The obtained data revealed that brain levels of the four measured neuropeptides were significantly reduced in PPA-treated animals compared to healthy control animals. Moreover, the findings demonstrate the ameliorative effects of bee pollen as a prebiotic and of the pure or mixed probiotics. This study proves the protective effects of pre and probiotics against the neurotoxic effects of PPA presented as impaired levels of α-MSH, β-End, NT, and SP.}, }
@article {pmid35735103, year = {2022}, author = {Qian, X and Zhang, HY and Li, QL and Ma, GJ and Chen, Z and Ji, XM and Li, CY and Zhang, AQ}, title = {Integrated microbiome, metabolome, and proteome analysis identifies a novel interplay among commensal bacteria, metabolites and candidate targets in non-small cell lung cancer.}, journal = {Clinical and translational medicine}, volume = {12}, number = {6}, pages = {e947}, pmid = {35735103}, issn = {2001-1326}, mesh = {Animals ; Bacteria/genetics ; *Carcinoma, Non-Small-Cell Lung ; Humans ; Inflammation ; *Lung Neoplasms ; Metabolome ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Proteome/pharmacology ; Tretinoin/pharmacology ; }, abstract = {BACKGROUND: Accumulation of evidence suggests that the gut microbiome, its specific metabolites, and differentially expressed proteins (DEPs) are related to non-small cell lung cancer (NSCLC) pathogenesis. We now report the influences of the gut microbiota, metabolites, and DEPs on the mediation of NSCLC's chronic inflammation and immune dysregulation.<br><br>METHODS: We conducted 16S ribosomal RNA sequencing for the gut microbiome in healthy volunteers and NSCLC patients. Liquid chromatography-mass spectrometry (LC-MS) analysis was employed to explore differences between metabolites and DEPs in serum samples. Additionally, LC-MS-based metabolomic analysis was conducted in 40 NSCLC tissues and 40 adjacent tissues. The omics data were separately analysed and integrated by using Spearman's correlation coefficient. Then, faecal microbiota transplantation (FMT) assay was used to assess the effects of the gut microbiome and specific metabolites in mice.<br><br>RESULTS: Faecal microbiome analysis revealed gut microflora dysbiosis in NSCLC patients with Prevotella, Gemmiger, and Roseburia significantly upregulated at the genus level. Then, we identified that nervonic acid/all-trans-retinoic acid level was negatively related to Prevotella. Additionally, a total of core 8 DEPs were selected in the proteome analysis, which mainly participated in the production of IL-8 and NF-&#x3ba;B pathways. CRP, LBP, and CD14 were identified as potential biomarkers for NSCLC. Transplantation of faecal microbiota from patients with NSCLC or Prevotella copri-colonized recipient in mice resulted in inflammation and immune dysregulation. In turn, nervonic acid/all-trans-retinoic acid treatment improved the phenotype of C57BL/6 mice bearing P. copri-treated Lewis lung cancer (LLC).<br><br>CONCLUSIONS: Overall, these results pointed out that P. copri-nervonic acid/all-trans-retinoic acid axis may contribute to the pathogenesis of NSCLC.}, }
@article {pmid35734396, year = {2022}, author = {Pu, D and Zhang, Z and Feng, B}, title = {Alterations and Potential Applications of Gut Microbiota in Biological Therapy for Inflammatory Bowel Diseases.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {906419}, pmid = {35734396}, issn = {1663-9812}, abstract = {Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract that is closely associated with dysbiosis of the intestinal microbiota. Currently, biologic agents are the mainstream therapies for IBD. With the increasing incidence of IBD, limitations of biologic agents have gradually emerged during treatment. Recent studies have indicated that gut microbiota is highly correlated with the efficacy of biologic agents. This review focuses on alterations in both the components and metabolites of gut microbiota during biological therapy for IBD, systematically summarises the specific gut microbiota closely related to the clinical efficacy, and compares current predictive models for the efficacy of biologics, further highlighting the predictive value of intestinal microbiota. Based on the mechanistic analysis of faecal microbiota transplantation (FMT) and biologic agents, a new therapeutic strategy, comprising a combination of FMT and biologics, has been proposed as a promising treatment for IBD with improved efficacy.}, }
@article {pmid35732628, year = {2022}, author = {Bao, J and Li, L and Zhang, Y and Wang, M and Chen, F and Ge, S and Chen, B and Yan, F}, title = {Periodontitis may induce gut microbiota dysbiosis via salivary microbiota.}, journal = {International journal of oral science}, volume = {14}, number = {1}, pages = {32}, pmid = {35732628}, issn = {2049-3169}, mesh = {Animals ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Mice ; Mice, Inbred C57BL ; *Microbiota ; *Periodontitis ; RNA, Ribosomal, 16S/genetics/metabolism ; }, abstract = {The aim of this study was to identify whether periodontitis induces gut microbiota dysbiosis via invasion by salivary microbes. First, faecal and salivary samples were collected from periodontally healthy participants (PH group, n = 16) and patients with severe periodontitis (SP group, n = 21) and analysed by 16S ribosomal RNA sequencing. Significant differences were observed in both the faecal and salivary microbiota between the PH and SP groups. Notably, more saliva-sourced microbes were observed in the faecal samples of the SP group. Then, the remaining salivary microbes were transplanted into C57BL6/J mice (the C-PH group and the C-SP group), and it was found that the composition of the gut microbiota of the C-SP group was significantly different from that of the C-PH group, with Porphyromonadaceae and Fusobacterium being significantly enriched in the C-SP group. In the colon, the C-SP group showed significantly reduced crypt depth and zonula occludens-1 expression. The mRNA expression levels of pro-inflammatory cytokines, chemokines and tight junction proteins were significantly higher in the C-SP group. To further investigate whether salivary bacteria could persist in the intestine, the salivary microbiota was stained with carboxyfluorescein diacetate succinimidyl ester and transplanted into mice. We found that salivary microbes from both the PH group and the SP group could persist in the gut for at least 24 h. Thus, our data demonstrate that periodontitis may induce gut microbiota dysbiosis through the influx of salivary microbes.}, }
@article {pmid35731859, year = {2022}, author = {Borody, TJ and Dolai, S and Gunaratne, AW and Clancy, RL}, title = {Targeting the microbiome in Crohn's disease.}, journal = {Expert review of clinical immunology}, volume = {18}, number = {9}, pages = {873-877}, doi = {10.1080/1744666X.2022.2093186}, pmid = {35731859}, issn = {1744-8409}, mesh = {*Crohn Disease ; Humans ; *Microbiota ; }, }
@article {pmid35721889, year = {2022}, author = {Kang, YB and Cai, Y}, title = {Future prospect of "Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients".}, journal = {World journal of gastroenterology}, volume = {28}, number = {20}, pages = {2248-2250}, pmid = {35721889}, issn = {2219-2840}, mesh = {*Carcinoma, Hepatocellular/pathology ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy/methods ; *Liver Neoplasms/pathology ; Nivolumab/therapeutic use ; }, abstract = {Recently, we read the article "Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients" with interest, and it is preliminary suggested that gut microbiota is closely related to therapeutic effect of nivolumab. Based on the meaningful results of this article, several valuable research directions are proposed to enhance the therapeutic effect of immune checkpoint inhibitors on advanced hepatocellular carcinoma.}, }
@article {pmid35721102, year = {2022}, author = {Zhang, J and Guo, Y and Duan, L}, title = {Features of Gut Microbiome Associated With Responses to Fecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {773105}, pmid = {35721102}, issn = {2296-858X}, abstract = {Fecal microbiota transplantation (FMT) has been seen as a novel treatment for inflammatory bowel disease (IBD). The results on microbial alterations and their relationship to treatment efficacy are varied among studies. We performed a systematic review to explore the association between microbial features and therapy outcomes. We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to November 2020. Studies that investigated the efficacy of FMT and baseline microbial features or dynamic alteration of the microbiome during FMT were included. The methodological quality of the included cohort studies and randomized controlled trials (RCTs) was assessed using the Newcastle-Ottawa Scale (NOS) and the Cochrane risk of bias tool, respectively. A total of 30 studies were included in the analysis. Compared to non-responders, the microbial structure of patients who responded to FMT had a higher similarity to that of their donors after FMT. Donors of responders (R-d) and non-responders (NR-d) had different microbial taxa, but the results were inconsistent. After FMT, several beneficial short-chain fatty acids- (SCFA-) producing taxa, such as Faecalibacterium, Eubacterium, Roseburia, and species belonging to them, were enriched in responders, while pathogenic bacteria (Escherichia coli and Escherichia-Shigella) belonging to the phylum Proteobacteria were decreased. Alterations of microbial functional genes and metabolites were also observed. In conclusion, the response to FMT was associated with the gut microbiota and their metabolites. The pre-FMT microbial features of recipients, the comparison of pre- and post-FMT microbiota, and the relationship between recipients and donors at baseline should be further investigated using uniform and standardized methods.}, }
@article {pmid35719863, year = {2022}, author = {Zhang, Y and Zhang, J and Pan, Z and He, X}, title = {Effects of Washed Fecal Bacteria Transplantation in Sleep Quality, Stool Features and Autism Symptomatology: A Chinese Preliminary Observational Study.}, journal = {Neuropsychiatric disease and treatment}, volume = {18}, number = {}, pages = {1165-1173}, pmid = {35719863}, issn = {1176-6328}, abstract = {PURPOSE: Autism spectrum disorder is a highly complex neurological and psychosocial disorder characterized by social dysfunction, severe reduction in speech, and a single stereotyped behavior. The treatment methods are currently limited, and children with autism generally suffer from constipation and sleep disorders. It is urgent to find an alternative psychotropic drug, given the drug dependence and adverse reactions that may occur with long-term medication.<br><br>PATIENTS AND METHODS: This retrospective study included 49 children with autism at the first affiliated Hospital of Guangdong Pharmaceutical University, who received washed fecal microbiota transplantation (WMT) treatment between June 2019 and July 2021 and compared the sleep disorder scores between the constipation group, control group and blank group.<br><br>RESULTS: Second WMT could significantly improve the sleep disorder scores in the constipation group (p=0.026) and the decrease in sleep disturbance scale for children (SDSC) score was synchronized with the increase in Bristol stool form scale (BSFS) score. However, there was no significant difference between patients without constipation (p=0.54), and the behavior of autism improved in both groups.<br><br>CONCLUSION: WMT could relieve constipation and improve sleep disorders in children with autism, with no deterioration in stool morphology and sleep disorders in other children. Moreover, there were no obvious serious adverse clinical events after WMT.}, }
@article {pmid35719145, year = {2022}, author = {Tan, J and Gong, J and Liu, F and Li, B and Li, Z and You, J and He, J and Wu, S}, title = {Evaluation of an Antibiotic Cocktail for Fecal Microbiota Transplantation in Mouse.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {918098}, pmid = {35719145}, issn = {2296-861X}, abstract = {OBJECTIVE: This study aimed to evaluate the effect of an antibiotic cocktail on gut microbiota and provide a reference for establishing an available mouse model for fecal microbiota transplantation (FMT) of specific microbes.<br><br>DESIGN: C57BL/6J mice (n = 24) had free access to an antibiotic cocktail containing vancomycin (0.5 g/L), ampicillin (1 g/L), neomycin (1 g/L), and metronidazole (1 g/L) in drinking water for 3 weeks. Fecal microbiota was characterized by 16S rDNA gene sequencing at the beginning, 1st week, and 3rd week, respectively. The mice were then treated with fecal microbiota from normal mice for 1 week to verify the efficiency of FMT.<br><br>RESULTS: The diversity of microbiota including chao1, observed species, phylogenetic diversity (PD) whole tree, and Shannon index were decreased significantly (P < 0.05) after being treated with the antibiotic cocktail for 1 or 3 weeks. The relative abundance of Bacteroidetes, Actinobacteria, and Verrucomicrobia was decreased by 99.94, 92.09, and 100%, respectively, while Firmicutes dominated the microbiota at the phylum level after 3 weeks of treatment. Meanwhile, Lactococcus, a genus belonging to the phylum of Firmicutes dominated the microbiota at the genus level with a relative abundance of 80.63%. Further FMT experiment indicated that the fecal microbiota from the receptor mice had a similar composition to the donor mice after 1 week.<br><br>CONCLUSION: The antibiotic cocktail containing vancomycin, ampicillin, neomycin, and metronidazole eliminates microbes belonging to Bacteroidetes, Actinobacteria, and Verrucomicrobia, which can be recovered by FMT in mice.}, }
@article {pmid35719141, year = {2022}, author = {Zhao, HJ and Zhang, XJ and Zhang, NN and Yan, B and Xu, KK and Peng, LH and Pan, F}, title = {Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {890357}, pmid = {35719141}, issn = {2296-861X}, abstract = {BACKGROUND: Gut microbiota has been identified as an imbalance in patients with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is a novel method to restore microbiota and treat IBS patients.<br><br>OBJECTIVE: To conduct a meta-analysis and estimate the efficacy and safety of FMT for the treatment of IBS patients with subgroup analyses to explore the most effective way of FMT for IBS.<br><br>METHODS: All eligible studies were searched from PubMed, Embase, Web of Science, and the Cochrane Library through multiple search strategies. Data were extracted from studies comprising the following criteria: double-blind, randomized controlled trials (RCTs) that compared the efficacy of FMT with placebo for adult patients (&#x2265;18 years old) with IBS. A meta-analysis was performed to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs).<br><br>RESULTS: A total of seven RCTs comprising 489 subjects were eligible for this meta-analysis. Pooled data showed no significant improvement of global IBS symptoms in patients with FMT compared with placebo (RR = 1.34; 95% CI 0.75-2.41, p = 0.32). A significant heterogeneity was observed among the studies (I [2] = 83%, p < 0.00001). There was no significant evidence of funnel plot asymmetry (Egger's test, p = 0.719; Begg's test, p = 1.000), indicating no existence of publication bias. Subgroup analyses revealed that FMT operated by invasive routes, including gastroscope, colonoscope, and nasojejunal tube, significantly improved global IBS symptoms (RR = 1.96; 95% CI 1.23-3.11, p = 0.004) with heterogeneity (I [2] = 57%, p = 0.06) and an NNT of 3 (95% CI 2-14). However, FMT delivered via oral capsules showed a negative impact on patients with IBS (RR = 0.56; 95% CI 0.33-0.96, p = 0.03) with a low heterogeneity (I [2] = 39%, p = 0.2) and an NNH of 3 (95% CI 2-37).<br><br>CONCLUSION: The current evidence from RCTs with all routes of FMT does not show significant global improvement in patients with IBS. However, FMT operated by invasive routes significantly improved global IBS symptoms.}, }
@article {pmid35716734, year = {2022}, author = {Qu, Z and Tian, P and Yang, B and Zhao, J and Wang, G and Chen, W}, title = {Fecal microbiota transplantation for diseases: Therapeutic potential, methodology, risk management in clinical practice.}, journal = {Life sciences}, volume = {304}, number = {}, pages = {120719}, doi = {10.1016/j.lfs.2022.120719}, pmid = {35716734}, issn = {1879-0631}, mesh = {Fecal Microbiota Transplantation/methods ; Feces ; *Gastrointestinal Diseases/etiology/therapy ; Humans ; *Metabolic Diseases/etiology ; Risk Management ; Treatment Outcome ; }, abstract = {BACKGROUND: More than 95 % of human diseases may be related to the disturbance of gut microbes. As a treatment method that extensively regulates the gut microbes, fecal microbiota transplantation (FMT) has proven to be an effective therapy for some diseases, becoming a topic of interest among clinicians, patients and scientists.<br><br>AIM: To review the latest clinical research results of FMT in the treatment of various diseases and the methodology and risk management in clinical application.<br><br>METHODS: Search PubMed and Web of Science for reliable research results of clinical treatment of FMT within 5-10&#xa0;years, as well as application guidelines and risk management policies in different regions.<br><br>RESULTS: As a measure of allogeneic/autologous microbiota transplantation, FMT has been used to treat a variety of diseases. By reviewing the clinical studies of FMT in gastrointestinal diseases, metabolic diseases, neurological diseases and malignant tumors, the various mechanisms in the treatment of diseases are summarized. Such as regulation of receptor microbiota composition, specific metabolites, phage function and immune response. In addition, potential risk factors, donor stool screening indicators, recipient self-specificity and possible prognostic marker molecules in the course of FMT treatment were generalized.<br><br>CONCLUSIONS: The potential regulatory mechanisms, risk factors and targets of FMT in gastrointestinal diseases, metabolic diseases, malignancies and neurological diseases were reviewed and proposed. It provides a theoretical basis for the establishment of a standardized treatment system for FMT and a breakthrough in treatment technology.}, }
@article {pmid35711246, year = {2022}, author = {Liu, Y and Chen, M}, title = {Clostridioides difficile Infection in Liver Cirrhosis: A Concise Review.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {2022}, number = {}, pages = {4209442}, pmid = {35711246}, issn = {2291-2797}, mesh = {*Clostridioides difficile ; *Clostridium Infections/epidemiology/prevention &amp; control ; Fecal Microbiota Transplantation/methods ; Humans ; Liver Cirrhosis/complications/therapy ; Recurrence ; Rifaximin ; Treatment Outcome ; }, abstract = {Clostridium difficile is a Gram-positive bacillus with fecal-oral transmission and is currently one of the most common nosocomial infections worldwide, which was renamed Clostridioides difficile in 2016. Clostridioides difficile infection (CDI) is a prevalent infection in cirrhosis and negatively affects prognosis. This study aimed to provide a concise review with clinical practice implications. The prevalence of CDI in cirrhotic patients increases, while the associated mortality decreases. Multiple groups of risk factors increase the likelihood of CDI in patients with cirrhosis, such as antibiotic use, the severity of cirrhosis, some comorbidities, and demographic aspects. Treatment in the general population is currently described in the latest guidelines. In patients with cirrhosis, rifaximin and lactulose have been shown to reduce CDI risk due to their modulatory effects on the intestinal flora, although conflicting results exist. Fecal microbiota transplantation (FMT) as a treatment for the second or subsequent CDI recurrences has demonstrated a good safety and efficacy in cirrhosis and CDI. Future validation in more prospective studies is needed. Screening of asymptomatic patients appears to be discouraged for the prevention currently, with strict hand hygiene and cleaning of the ward and medical equipment surfaces being the cornerstone of minimizing transmission.}, }
@article {pmid35711026, year = {2023}, author = {Kim, A and Zisman, CR and Holingue, C}, title = {Influences of the Immune System and Microbiome on the Etiology of ASD and GI Symptomology of Autistic Individuals.}, journal = {Current topics in behavioral neurosciences}, volume = {61}, number = {}, pages = {141-161}, pmid = {35711026}, issn = {1866-3370}, mesh = {Humans ; *Autistic Disorder ; *Autism Spectrum Disorder ; Gastrointestinal Tract ; *Microbiota ; Immune System ; }, abstract = {Autism Spectrum Disorder is a developmental condition associated with impairments in communication and social interactions, and repetitive and restricted behavior or interests. Autistic individuals are more likely to experience gastrointestinal (GI) symptoms than neurotypical individuals. This may be partially due to dysbiosis of the gut microbiome. In this article, we describe the interaction of the microbiome and immune system on autism etiology. We also summarize the links between the microbiome and gastrointestinal and related symptoms among autistic individuals. We report that microbial interventions, including diet, probiotics, antibiotics, and fecal transplants, and immune-modulating therapies such as cytokine blockade during the preconception, pregnancy, and postnatal period may impact the neurodevelopment, behavior, and gastrointestinal health of autistic individuals.}, }
@article {pmid35710492, year = {2022}, author = {Zhong, W and Wu, K and Long, Z and Zhou, X and Zhong, C and Wang, S and Lai, H and Guo, Y and Lv, D and Lu, J and Mao, X}, title = {Gut dysbiosis promotes prostate cancer progression and docetaxel resistance via activating NF-κB-IL6-STAT3 axis.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {94}, pmid = {35710492}, issn = {2049-2618}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Docetaxel/pharmacology ; *Dysbiosis/microbiology ; Feces/microbiology ; Humans ; Interleukin-6 ; Lipopolysaccharides ; Male ; Mice ; NF-kappa B ; *Prostatic Neoplasms ; Proteobacteria/genetics ; RNA, Ribosomal, 16S/genetics ; STAT3 Transcription Factor/genetics ; }, abstract = {BACKGROUND: The gut microbiota is reportedly involved in the progression and chemoresistance of various human malignancies. However, the underlying mechanisms behind how it exerts some effect on prostate cancer, as an extra-intestinal tumor, in a contact-independent way remain elusive and deserve exploration. Antibiotic exposure, one of the various factors affecting the gut microbiota community and capable of causing gut dysbiosis, is associated with multiple disorders. This study aims to preliminarily clarify the link between gut dysbiosis and prostate cancer.<br><br>RESULTS: First, we discovered that perturbing the gut microbiota by consuming broad-spectrum antibiotics in water promoted the growth of subcutaneous and orthotopic tumors in mice. Fecal microbiota transplantation could transmit the effect of antibiotic exposure on tumor growth. Then, 16S rRNA sequencing for mouse feces indicated that the relative abundance of Proteobacteria was significantly higher after antibiotic exposure. Meanwhile, intratumoral lipopolysaccharide (LPS) profoundly increased under the elevation of gut permeability. Both in vivo and in vitro experiments revealed that the NF-&#x3ba;B-IL6-STAT3 axis activated by intratumoral LPS facilitated prostate cancer proliferation and docetaxel chemoresistance. Finally, 16S rRNA sequencing of patients' fecal samples revealed that Proteobacteria was enriched in patients with metastatic prostate cancer and was positively correlated with plasma IL6 level, regional lymph node metastasis status, and distant metastasis status. The receiver operating characteristic (ROC) curves showed that the relative abundance of Proteobacteria had better performance than the prostate-specific antigen (PSA) level in predicting the probability of distant metastasis in prostate cancer (area under the ROC curve, 0.860; p < 0.001).<br><br>CONCLUSION: Collectively, this research demonstrated that gut dysbiosis, characterized by the enrichment of Proteobacteria due to antibiotic exposure, resulted in the elevation of gut permeability and intratumoral LPS, promoting the development of prostate cancer via the NF-&#x3ba;B-IL6-STAT3 axis in mice. Considering findings from human patients, Proteobacteria might act as an intestinal biomarker for progressive prostate cancer. Video Abstract.}, }
@article {pmid35710014, year = {2022}, author = {Wen, S and Zhao, Y and Liu, S and Chen, Y and Yuan, H and Xu, H}, title = {Polystyrene microplastics exacerbated liver injury from cyclophosphamide in mice: Insight into gut microbiota.}, journal = {The Science of the total environment}, volume = {840}, number = {}, pages = {156668}, doi = {10.1016/j.scitotenv.2022.156668}, pmid = {35710014}, issn = {1879-1026}, mesh = {Animals ; Cyclophosphamide/toxicity ; *Gastrointestinal Microbiome ; Inflammation ; Liver ; Mice ; *Microplastics ; Plastics/toxicity ; Polystyrenes/toxicity ; }, abstract = {Microplastics (MPs) have infiltrated human food system globally, and the latent health risks have been well-described. However, the impact of pre-consumed MPs on liver resistance to foreign robust stimuli remains unclear. In this study, we developed a mouse model drinking roughly 18 and 180 μg/kg/day polystyrene MPs for 90 days, then intraperitoneally injected mice with 80 mg/kg cyclophosphamide (CTX) to investigate whether chronic pre-exposure to MPs aggravates hepatoxicity induced by CTX. Slight liver injury was found in single CTX-treated mice, while more significant liver histopathological damage, inflammation and oxidative stress elicited by CTX were observed in pre-drinking MPs mice. Moreover, chronic exposure of MPs induced remarkable colonic impairments (e.g., leaky gut, mild inflammation and repressed antioxidant activity) as well as gut microbiota perturbation, which manifested positive association with aggravated hepatotoxicity via spearman correlation analysis. Fecal microbiota transplantation (FMT) trail was conducted to ulteriorly demonstrate the critical role of MPs-altered gut bacteria in exaggerated liver susceptibility to CTX stimulation. In conclusion, our study provided an insight that the adverse impact of MPs could be best revealed when animals suffering attack from hazardous substance. It also contributes to comprehensive assessment of health risk from environmentally pervasive MPs.}, }
@article {pmid35709830, year = {2022}, author = {El-Salhy, M and Winkel, R and Casen, C and Hausken, T and Gilja, OH and Hatlebakk, JG}, title = {Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation.}, journal = {Gastroenterology}, volume = {163}, number = {4}, pages = {982-994.e14}, doi = {10.1053/j.gastro.2022.06.020}, pmid = {35709830}, issn = {1528-0012}, mesh = {Bacteria ; DNA ; Dysbiosis/microbiology ; Fatigue/etiology ; Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/physiology ; Humans ; *Irritable Bowel Syndrome/microbiology ; Male ; Quality of Life ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: The long-term efficacy and possible adverse events of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS) are unknown. This study performed a 3-year follow-up of the patients in our previous clinical trial to clarify these aspects.<br><br>METHODS: This study included 125 patients (104 females, and 21 males): 38 in a placebo group, 42 who received 30 g of donor feces, and 45 who received 60 g of donor feces. Feces was administered to the duodenum. The patients provided a fecal sample and completed 5 questionnaires at baseline and at 2 and 3 years after FMT. Fecal bacteria and dysbiosis index were analyzed using 16S ribosomal RNA gene polymerase chain reaction DNA amplification/probe hybridization covering the V3 to V9 regions.<br><br>RESULTS: Response rates were 26.3%, 69.1%, and 77.8% in the placebo, 30-g, and 60-g groups, respectively, at 2 years after FMT, and 27.0%, 64.9%, and 71.8%, respectively, at 3 years after FMT. The response rates were significantly higher in the 30-g and 60-g groups than in the placebo group. Patients in the 30-g and 60-g groups had significantly fewer IBS symptoms and fatigue, and a greater quality of life both at 2 and 3 years after FMT. The dysbiosis index decreased only in the active treatment groups at 2 and 3 years after FMT. Fluorescent signals of 10 bacteria had significant correlations with IBS symptoms and fatigue after FMT in the 30-g and 60-g groups. No long-term adverse events were recorded.<br><br>CONCLUSIONS: FMT performed according to our protocol resulted in high response rates and long-standing effects with only few mild self-limited adverse events. This study was registered at www.<br><br>CLINICALTRIALS: gov (NCT03822299).}, }
@article {pmid35709819, year = {2022}, author = {Mullish, BH and McDonald, JAK and Marchesi, JR}, title = {Intestinal microbiota transplantation: do not forget the metabolites.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {7}, pages = {594}, doi = {10.1016/S2468-1253(22)00101-7}, pmid = {35709819}, issn = {2468-1253}, support = {MC_PC_17162/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid35709800, year = {2022}, author = {Tian, H and Zhang, S and Qin, H and Li, N and Chen, Q and , }, title = {Long-term safety of faecal microbiota transplantation for gastrointestinal diseases in China.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {8}, pages = {702-703}, doi = {10.1016/S2468-1253(22)00170-4}, pmid = {35709800}, issn = {2468-1253}, mesh = {China/epidemiology ; *Colitis, Ulcerative ; Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Diseases/therapy ; Humans ; }, }
@article {pmid35709780, year = {2022}, author = {Kindt, S and Louis, H and De Schepper, H and Arts, J and Caenepeel, P and De Looze, D and Gerkens, A and Holvoet, T and Latour, P and Mahler, T and Mokaddem, F and Nullens, S and Piessevaux, H and Poortmans, P and Rasschaert, G and Surmont, M and Vafa, H and Van Malderen, K and Vanuytsel, T and Wuestenberghs, F and Tack, J}, title = {Belgian consensus on irritable bowel syndrome.}, journal = {Acta gastro-enterologica Belgica}, volume = {85}, number = {2}, pages = {360-382}, doi = {10.51821/85.2.10100}, pmid = {35709780}, issn = {1784-3227}, mesh = {Humans ; Belgium/epidemiology ; Consensus ; Constipation/drug therapy ; Diarrhea ; *Irritable Bowel Syndrome/diagnosis/epidemiology/etiology ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice.<br><br>METHODS: A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement.<br><br>RESULTS: Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged.<br><br>CONCLUSIONS: A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.}, }
@article {pmid35705368, year = {2023}, author = {Awoniyi, M and Wang, J and Ngo, B and Meadows, V and Tam, J and Viswanathan, A and Lai, Y and Montgomery, S and Farmer, M and Kummen, M and Thingholm, L and Schramm, C and Bang, C and Franke, A and Lu, K and Zhou, H and Bajaj, JS and Hylemon, PB and Ting, J and Popov, YV and Hov, JR and Francis, HL and Sartor, RB}, title = {Protective and aggressive bacterial subsets and metabolites modify hepatobiliary inflammation and fibrosis in a murine model of PSC.}, journal = {Gut}, volume = {72}, number = {4}, pages = {671-685}, pmid = {35705368}, issn = {1468-3288}, support = {R01 DK108959/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; I01 CX001076/CX/CSRD VA/United States ; K01 DK119582/DK/NIDDK NIH HHS/United States ; I01 BX005730/BX/BLRD VA/United States ; IS1 BX004777/BX/BLRD VA/United States ; U19 AI067798/AI/NIAID NIH HHS/United States ; I01 BX003031/BX/BLRD VA/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; R01 DK115377/DK/NIDDK NIH HHS/United States ; I01 BX004033/BX/BLRD VA/United States ; R35 CA232109/CA/NCI NIH HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; R21 TR003095/TR/NCATS NIH HHS/United States ; I01 BX001328/BX/BLRD VA/United States ; P01 DK094779/DK/NIDDK NIH HHS/United States ; R21 AA026629/AA/NIAAA NIH HHS/United States ; IK6 BX004477/BX/BLRD VA/United States ; P40 OD010995/OD/NIH HHS/United States ; R01 DK119421/DK/NIDDK NIH HHS/United States ; IK6 BX005226/BX/BLRD VA/United States ; R01 DK104893/DK/NIDDK NIH HHS/United States ; R01 DK057543/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Vancomycin ; Disease Models, Animal ; *Escherichia coli ; RNA, Ribosomal, 16S/genetics ; Inflammation ; Liver Cirrhosis ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Clostridiales ; }, abstract = {OBJECTIVE: Conflicting microbiota data exist for primary sclerosing cholangitis (PSC) and experimental models.<br><br>GOAL: define the function of complex resident microbes and their association relevant to PSC patients by studying germ-free (GF) and antibiotic-treated specific pathogen-free (SPF) multidrug-resistant 2 deficient (mdr2[-/-]) mice and microbial profiles in PSC patient cohorts.<br><br>DESIGN: We measured weights, liver enzymes, RNA expression, histological, immunohistochemical and fibrotic biochemical parameters, faecal 16S rRNA gene profiling and metabolomic endpoints in gnotobiotic and antibiotic-treated SPF mdr2[-/-] mice and targeted metagenomic analysis in PSC patients.<br><br>RESULTS: GF mdr2[-/-] mice had 100% mortality by 8&#x2009;weeks with increasing hepatic bile acid (BA) accumulation and cholestasis. Early SPF autologous stool transplantation rescued liver-related mortality. Inhibition of ileal BA transport attenuated antibiotic-accelerated liver disease and decreased total serum and hepatic BAs. Depletion of vancomycin-sensitive microbiota exaggerated hepatobiliary disease. Vancomycin selectively decreased Lachnospiraceae and short-chain fatty acids (SCFAs) but expanded Enterococcus and Enterobacteriaceae. Antibiotics increased Enterococcus faecalis and Escherichia coli liver translocation. Colonisation of GF mdr2[-/-] mice with translocated E. faecalis and E. coli strains accelerated hepatobiliary inflammation and mortality. Lachnospiraceae colonisation of antibiotic pretreated mdr2[-/-] mice reduced liver fibrosis, inflammation and translocation of pathobionts, and SCFA-producing Lachnospiraceae and purified SCFA decreased fibrosis. Faecal Lachnospiraceae negatively associated, and E. faecalis/ Enterobacteriaceae positively associated, with PSC patients' clinical severity by Mayo risk scores.<br><br>CONCLUSIONS: We identified novel functionally protective and detrimental resident bacterial species in mdr2[-/-] mice and PSC patients with associated clinical risk score. These insights may guide personalised targeted therapeutic interventions in PSC patients.}, }
@article {pmid35701543, year = {2022}, author = {Benech, N and Sokol, H}, title = {Specific gut microbiota taxa as a key source of variability in colitis model.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {19}, number = {8}, pages = {491-492}, pmid = {35701543}, issn = {1759-5053}, mesh = {Animals ; *Colitis ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Humans ; Mice ; Mice, Inbred C57BL ; }, }
@article {pmid35700921, year = {2023}, author = {Ge, X and He, X and Liu, J and Zeng, F and Chen, L and Xu, W and Shao, R and Huang, Y and Farag, MA and Capanoglu, E and El-Seedi, HR and Zhao, C and Liu, B}, title = {Amelioration of type 2 diabetes by the novel 6, 8-guanidyl luteolin quinone-chromium coordination via biochemical mechanisms and gut microbiota interaction.}, journal = {Journal of advanced research}, volume = {46}, number = {}, pages = {173-188}, pmid = {35700921}, issn = {2090-1224}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/drug therapy ; Luteolin/pharmacology/therapeutic use ; Peroxisome Proliferator-Activated Receptors/pharmacology/therapeutic use ; Hypoglycemic Agents/pharmacology/therapeutic use ; Quinones/pharmacology/therapeutic use ; Glucose/pharmacology/therapeutic use ; *Hyperglycemia/drug therapy ; }, abstract = {INTRODUCTION: Luteolin is a plant-derived flavonoid that exhibits a broad range of pharmacological activities. Studies on luteolin have mainly focused on its use for hyperlipidaemia prevention, whereas the capacity of the flavonoid to hinder hyperglycaemia development remains underexplored.<br><br>OBJECTIVES: To probe the anti-hyperglycemic mechanism of 6,8-guanidyl luteolin quinone-chromium coordination (GLQ.Cr), and to assess its regulatory effect on intestinal microbiota in type 2 diabetes mellitus (T2DM) mice.<br><br>METHODS: High-sucrose/high-fat diet-induced and intraperitoneal injection of streptozotocin was used to develop a T2DM model. Glycometabolism related indicators, histopathology, and gut microbiota composition in caecum samples were evaluated, and RNA sequencing (RNA-seq) of liver samples was conducted. Faecal microbiota transplantation (FMT) was further used to verify the anti-hyperglycemic activity of intestinal microbiota.<br><br>RESULTS: The administration of GLQ.Cr alleviated hyperglycaemia symptoms by improving liver and pancreatic functions and modulating gut microbe communities (Lactobacillus, Alistipes, Parabacteroides, Lachnoclostridium, and Desulfovibrio). RNA-seq analysis showed that GLQ.Cr mainly affected the peroxisome proliferative activated receptor (PPAR) signalling pathway in order to regulate abnormal glucose metabolism. FMT significantly modulated the abundance of Lactobacillus, Alloprevotella, Alistipes, Bacteroides, Ruminiclostridium, Brevundimonas and Pseudomonas in the caecum to balance blood glucose levels and counteract T2DM mice inflammation.<br><br>CONCLUSION: GLQ.Cr improved the abnormal glucose metabolism in T2DM mice by regulating the PPAR signalling pathway and modulating intestinal microbial composition. FMT can improve the intestinal microecology of the recipient and in turn ameliorate the symptoms of T2DM-induced hyperglycaemia.}, }
@article {pmid35700156, year = {2022}, author = {Rashidi, A and Karuppiah, S and Ebadi, M and Shanley, R and Khoruts, A and Weisdorf, DJ and Staley, C}, title = {A dose-finding safety and feasibility study of oral activated charcoal and its effects on the gut microbiota in healthy volunteers not receiving antibiotics.}, journal = {PloS one}, volume = {17}, number = {6}, pages = {e0269986}, pmid = {35700156}, issn = {1932-6203}, support = {P30 CA077598/CA/NCI NIH HHS/United States ; KL2 TR002492/TR/NCATS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/adverse effects ; Charcoal/pharmacology ; Feasibility Studies ; Feces ; *Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Oral activated charcoal (OAC), a potent adsorbent with no systemic absorption, has been used for centuries to treat poisoning. Recent studies have suggested its potential efficacy in protecting the colonic microbiota against detrimental effects of antibiotics. In a dose-finding safety and feasibility clinical trial, 12 healthy volunteers not receiving antibiotics drank 4 different preparations made of 2 possible OAC doses (12 or 25 grams) mixed in 2 possible solutions (water or apple juice), 3 days a week for 2 weeks. Pre- and post-OAC stool samples underwent 16S rRNA gene sequencing and exact amplicon sequence variants were used to characterize the colonic microbiota. The preferred preparation was 12 grams of OAC in apple juice, with excellent safety and tolerability. OAC did not influence the gut microbiota in our healthy volunteers. These findings provide the critical preliminary data for future trials of OAC in patients receiving antibiotics.}, }
@article {pmid35698418, year = {2022}, author = {Zhou, W and Yang, T and Xu, W and Huang, Y and Ran, L and Yan, Y and Mi, J and Lu, L and Sun, Y and Zeng, X and Cao, Y}, title = {The polysaccharides from the fruits of Lycium barbarum L. confer anti-diabetic effect by regulating gut microbiota and intestinal barrier.}, journal = {Carbohydrate polymers}, volume = {291}, number = {}, pages = {119626}, doi = {10.1016/j.carbpol.2022.119626}, pmid = {35698418}, issn = {1879-1344}, mesh = {Animals ; Caco-2 Cells ; *Diabetes Mellitus, Experimental/chemically induced/drug therapy ; Fruit ; *Gastrointestinal Microbiome ; Humans ; *Lycium ; Mice ; Polysaccharides/pharmacology/therapeutic use ; }, abstract = {The antidiabetic effect and potential mechanisms of the polysaccharides from the fruits of Lycium barbarum L. (LBPs) by the mouse model of high-fat diet/streptozotocin-induced diabetes were investigated. Six-week oral administration of LBPs (200 mg/kg/day) resulted in improvement in the levels of fasting blood glucose (13.51% decrease) and glycated hemoglobin and β-cell function in diabetic mice, and simultaneously induced a 3.3-fold increment in one taxon belonging to genus Allobaculum in gut bacterial community. The experiments of fecal microbiota transplantation and antibiotics treatment confirmed that the LBPs-mediated gut microbiota participated in the glycemic control of the diabetes management. Moreover, LBPs intervention guarded the intestinal barrier function via upregulating the expression of zonula occludens 1 both in vivo (analyzing the gut permeability in diabetic mice) and in vitro (using intestinal-like Caco-2/RAW264.7 cells co-culture inflammation model). Collectively, our study showed that LBPs could confer anti-diabetic effect through modifying gut microbiota and intestinal barrier.}, }
@article {pmid35697204, year = {2022}, author = {Kattner, AA}, title = {A finger in every pie - The versatility of chemokines.}, journal = {Biomedical journal}, volume = {45}, number = {3}, pages = {427-431}, pmid = {35697204}, issn = {2320-2890}, mesh = {COVID-19 ; *Chemokines/physiology ; Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; Treatment Outcome ; }, abstract = {In this issue of Biomedical Journal we encounter the chemokine superfamily and its clinical potential. The time course from 56 days zero COVID-19 to a resurgence in cases is presented, as well as a possible solution to overcome rejection in vascularized composite allotransplantation. We are shown the opportunity deep learning (DL) offers in the case of tracking single cells and particles, and also use of DL to bring all hands on deck to counter the current challenge of the COVID-19 pandemic. This issue contains articles about the effect of low energy shock waves in cystitis; the negative effect of high fructose on aortic valve stenosis; a study about the outcome of fecal microbiota transplantation in case of refractory Clostridioides difficile infection; a novel long non-coding RNA that could serve in treating triple-negative breast cancer; the benefits of acupressure in patients with restless leg syndrome; and Filamin A mutations in abnormal neuronal migration development. Finally, a link between jaw surgery and the psychological impact on the patient is explored; a method presented that allows identification of cervical characteristics associated with difficult embryo transfer; and a letter suggesting new parameters to evaluate the use of bone-substitute augmentation in the treatment of osteoporotic intertrochanteric fractures.}, }
@article {pmid35695221, year = {2023}, author = {Liu, T and Su, D and Lei, C and Liu, Z}, title = {Treatment of Radiation Enteritis With Fecal Transplantation.}, journal = {The American surgeon}, volume = {89}, number = {6}, pages = {2999-3001}, doi = {10.1177/00031348221091954}, pmid = {35695221}, issn = {1555-9823}, mesh = {Humans ; Female ; Middle Aged ; Adolescent ; Fecal Microbiota Transplantation ; Feces ; Neoplasm Recurrence, Local ; *Enteritis/etiology/therapy ; *Gastrointestinal Microbiome ; *Radiation Injuries/therapy ; Treatment Outcome ; *Clostridium Infections ; }, abstract = {Radiation enteritis (RE) is a frequent complication in patients who undergo pelvic irradiation, and this condition has been increasingly diagnosed. Fecal microbiota transplantation (FMT) is being developed in recent years, and it has remarkable curative effect for the clostridium and inflammatory bowel disease. Herein, we present a case of recurrent RE in a 59-year-old woman with RE 18 years after radiotherapy for cervical carcinoma. Fecal microbiota transplantation therapy with intestinal flora from her 18-year-old son was applied and was successful in relieving the symptoms. To the best of our knowledge, this study is the first case report of FMT in a patient with RE.}, }
@article {pmid35694271, year = {2022}, author = {Cai, M and Xiao, Y and Lin, Z and Lu, J and Wang, X and Rahman, SU and Zhu, S and Chen, X and Gu, J and Ma, Y and Chen, Z and Huo, J}, title = {Disordered Gut Microbiota in Colorectal Tumor-Bearing Mice Altered Serum Metabolome Related to Fufangchangtai.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {889181}, pmid = {35694271}, issn = {1663-9812}, abstract = {Purpose: This study aimed to investigate the relationship between gut microbiota (GM) and serum metabolism using antineoplastic Fufangchangtai (FFCT) as the model prescription in the treatment of colorectal cancer (CRC). Methods: Tumor-bearing mice and normal mice were administered different doses of FFCT. The tumor volume of tumor-bearing mice was observed. The levels of CD4[+] and CD8[+] T cells in the blood, spleen, and tumor of mice were determined using a flow cytometer. The bacterial microbiota in stool samples from mice and the serum metabolomics of FFCT-treated mice and fecal microbiota transplantation mice were detected using 16s RNA sequencing and liquid chromatography-mass spectrometry (LC/MS), respectively. Results: The tumor volume of mice showed no significant decrease after FFCT intervention. The levels of CD4[+] and CD8[+]T lymphocytes showed a significant increase under the intervention of FFCT. GM of colorectal tumor-bearing mice and healthy mice were determined, and the diversity and abundance of Firmicutes, Deferribacteres, Bacteroidetes, and Proteobacteria were significantly different between the two groups. Furthermore, we found that the levels of matrine, isogingerenone B, and armillaripin were significantly decreased in tumor-bearing mice after FFCT intervention, indicating that the tumor-induced dysbiosis of gut bacteria may affect the absorption and metabolism of FFCT. Under the intervention of FFCT, serum metabolism of mice transplanted with feces from CRC patients showed less metabolites related to FFCT than that from healthy people, indicating that GM could be a single factor affecting the metabolism of FFCT. Furthermore, we found that different doses of FFCT-treated mice had higher abundance of Roseburia, Turicibacter, and Flexispira than that in the non-intervention control group. Firmicutes and Bacteroidetes in FFCT-treated groups showed a similar trend compared to the healthy group, indicating that FFCT might correct the intestinal microenvironment by modulating gut microbiota in colorectal tumor-bearing mice. Conclusion: The dysbiosis of GM in tumor-bearing mice reduced the serum metabolites related to FFCT, and FFCT could correct the disordered GM of colorectal tumor-bearing mice to exert efficacy.}, }
@article {pmid35693372, year = {2022}, author = {Gupta, K and Tappiti, M and Nazir, AM and Koganti, B and Memon, MS and Aslam Zahid, MB and Shantha Kumar, V and Mostafa, JA}, title = {Fecal Microbiota Transplant in Recurrent Clostridium Difficile Infections: A Systematic Review.}, journal = {Cureus}, volume = {14}, number = {5}, pages = {e24754}, pmid = {35693372}, issn = {2168-8184}, abstract = {Fecal Microbiota Transplantation (FMT) is the process of transferring the fecal microbiome from a healthy donor to an individual with repeated multiple episodes of Clostridium difficile infection. It is also known as stool transplant. Fecal microbiota transplant is effective and safe in various studies, the approval from the Food and Drug Administration (FDA) remains pending. The main objective of this systemic review is to evaluate the efficacy and safety of stool transplant in studies with only treatment groups (FMT) and studies with treatment (FMT) and antibiotic (AB) groups and previous studies. Online databases PubMed, PubMed Central, Science Direct, Google Scholar, and Embase were searched for relevant articles in the last five years (2016 to 2021) using automation tools. Following the removal of duplicates, screening of eligibility criteria, titles/abstracts, and quality appraisal were done by two authors independently. In total, seven observational studies are in this review article. Out of the seven observational studies, five are retrospective and two prospective. Two of the five retrospective and one of two prospective studies have a control group. In both the prospective studies and one retrospective study, FMT efficacy of (68% to 93%) was demonstrated in the elderly population despite high index comorbidities. In the younger individuals with inflammatory bowel disease, and efficacy of 90% or above was found. The most common side effects were minor such as fever, abdominal pain, bloating, and flatulence. In one study, two cases of aspiration events occurred attributed to the gastroscopy route of donor feces delivery. There was no statistical significance in the incidence of diseases such as (allergies, autoimmune diseases, cancer, inflammatory bowel diseases, and neurological diseases like dementia and migraine). Fecal microbiota transplantation has shown to be effective and safe in recurrent Clostridium difficile infections. Since very few pragmatic studies have demonstrated its efficacy and safety, their application is not well established. Robust studies, both observation and experiment, are required in the future to well-establish its effectiveness, safety in the treatment of recurrent Clostridium difficile infection.}, }
@article {pmid35691195, year = {2022}, author = {Li, T and Tian, D and Lu, M and Wang, B and Li, J and Xu, B and Chen, H and Wu, S}, title = {Gut microbiota dysbiosis induced by polychlorinated biphenyl 126 contributes to increased brain proinflammatory cytokines: Landscapes from the gut-brain axis and fecal microbiota transplantation.}, journal = {Ecotoxicology and environmental safety}, volume = {241}, number = {}, pages = {113726}, doi = {10.1016/j.ecoenv.2022.113726}, pmid = {35691195}, issn = {1090-2414}, mesh = {Animals ; Bacteria/metabolism ; Brain/metabolism ; Brain-Gut Axis ; Cytokines/metabolism ; Dysbiosis/chemically induced ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Lipopolysaccharides ; Mice ; *Polychlorinated Biphenyls/toxicity ; Toll-Like Receptor 4/genetics/metabolism ; }, abstract = {The pathogenesis of brain inflammation induced by polychlorinated biphenyl 126 (PCB126) has not yet been fully illustrated. Growing evidence highlights the relevance of the microbiota-gut-brain axis in central nervous system (CNS) dysfunction. Therefore, we aimed to study the role of the gut microbiota in PCB126-induced proinflammatory cytokine increases in the mouse brain. The results showed that PCB126 exposure significantly disordered gut bacterial communities, resulting in the enrichment of gram-negative bacteria (e.g., Bacteroidetes and Proteobacteria), further leading to elevated levels of the gram-negative bacterial lipopolysaccharide (LPS). Subsequently, colonic toll-like receptor 4 (TLR-4) was activated by bacterial LPS, which promoted proinflammatory cytokine generation and inhibited tight junction (TJ) protein expression. Then, bacterial LPS translocated from the gut lumen into the blood circulation and reached the brain, triggering LPS/TLR-4-mediated increases in brain proinflammatory cytokines. Further analysis after fecal microbiota transplantation (FMT) suggested that the gut microbiota disturbance caused by PCB126 could induce elevated bacterial LPS and trigger TLR-4-mediated increases in proinflammatory cytokines in the brain. This study highlights the possibility that PCB126-induced gut microbiota disorder contributes to increased brain proinflammatory cytokines. These results provide a new perspective for identifying the toxicity mechanisms of PCB126 and open up the possibility of modulating the gut microbiota as a therapeutic target for CNS disease caused by environmental pollution.}, }
@article {pmid35690527, year = {2022}, author = {Huang, C and Yi, P and Zhu, M and Zhou, W and Zhang, B and Yi, X and Long, H and Zhang, G and Wu, H and Tsokos, GC and Zhao, M and Lu, Q}, title = {Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial.}, journal = {Journal of autoimmunity}, volume = {130}, number = {}, pages = {102844}, doi = {10.1016/j.jaut.2022.102844}, pmid = {35690527}, issn = {1095-9157}, mesh = {Antibodies, Antinuclear ; Dysbiosis/therapy ; Fatty Acids, Volatile ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Humans ; *Lupus Erythematosus, Systemic/therapy ; Treatment Outcome ; }, abstract = {Gut microbiota dysbiosis is involved in the development of systemic lupus erythematosus (SLE). The safety and efficacy of fecal microbiota transplantation (FMT) for the treatment of SLE patients has not been explored. In this 12-week, single-arm pilot clinical trial of oral encapsulated fecal microbiome from healthy donors to patients with active SLE, we aimed to evaluate the safety and efficacy of FMT in patients with SLE (ChiCTR2000036352). 20 SLE patients with SLEDAI ≥6 were recruited. FMT was administered once a week for three consecutive weeks along with standard treatment and the patients were followed for 12 weeks. Safety was evaluated throughout the trial. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. Microbiome composition, levels of short chain fatty acids (SCFAs) in the gut and of cytokines in the sera were measured along with lymphocyte phenotyping. No serious adverse events were observed after FMT. At week 12, the SRI-4 response rate was 42.12%, and significant reductions in the SLEDAI-2K scores and the level of serum anti-dsDNA antibody were observed compared to baseline. Significant enrichment of SCFAs-producing bacterial taxa and reduction of inflammation-related bacterial taxa were observed, along with increased production of SCFAs in the gut and reduced levels of IL-6 and CD4[+] memory/naïve ratio in the peripheral blood. Furthermore, SRI-4 responding patients displayed specific microbiota signatures both before and after FMT. The first clinical trial of FMT in active SLE patients provide supportive evidence that FMT might be a feasible, safe, and potentially effective therapy in SLE patients by modifying the gut microbiome and its metabolic profile.}, }
@article {pmid35690329, year = {2022}, author = {Gu, Y and Wang, C and Qin, X and Zhou, B and Liu, X and Liu, T and Xie, R and Liu, J and Wang, B and Cao, H}, title = {Saccharomyces boulardii, a yeast probiotic, inhibits gut motility through upregulating intestinal serotonin transporter and modulating gut microbiota.}, journal = {Pharmacological research}, volume = {181}, number = {}, pages = {106291}, doi = {10.1016/j.phrs.2022.106291}, pmid = {35690329}, issn = {1096-1186}, mesh = {Animals ; Bacteria/metabolism ; ErbB Receptors/metabolism ; *Gastrointestinal Microbiome ; Heparin-binding EGF-like Growth Factor/metabolism ; *Irritable Bowel Syndrome ; Mice ; *Probiotics/pharmacology ; *Saccharomyces boulardii/metabolism ; Serotonin/metabolism ; Serotonin Plasma Membrane Transport Proteins/genetics/metabolism ; }, abstract = {Saccharomyces boulardii (Sb) is a widely used fungal probiotic in treating various digestive diseases, including irritable bowel syndrome (IBS). However, the specific mechanisms of Sb relieving IBS remain unclear. The abnormal serotonin transporter (SERT) / 5-hydroxytryptamine (5-HT) system could cause disordered gastrointestinal sensation and motility, which closely related to IBS pathogenesis. The aim of this study was to explore the effects and mechanisms of Sb on regulating gut motility. Sb supernatant (SbS) was administered to intestinal epithelial cells and mice. SbS upregulated SERT expression via enhancing heparin-binding epidermal growth factor (HB-EGF) release to activate epidermal growth factor receptor (EGFR). EGFR kinase inhibitor treatment or HB-EGF siRNA transfection in cells blocked SbS upregulating SERT. Consistently, SbS-treated mice presented inhibited gut motility, and EGFR activation and SERT upregulation were found. Moreover, 16 S rDNA sequence presented an evident decrease in Firmicutes / Bacteroidetes ratio in SbS group. In genus level, SbS reduced Escherichia_Shigella, Alistipes, Clostridium XlVa, and Saccharibacteria_genera_incertae_sedis, meanwhile, increased Parasutterella. The abundance of Saccharibacteria_genera_incertae_sedis positively correlated with defecation parameters and intestinal 5-HT content. Fecal microbiota transplantation showed that SbS could modulate gut microbiota to influence gut motility. Interestingly, elimination of gut microbiota with antibiotic cocktail did not entirely block SbS regulating gut motility. Furthermore, SbS administration to IBS-D mice significantly upregulated SERT and inhibited gut motility. In conclusion, SbS could upregulate SERT by EGFR activation, and modulate gut microbiota to inhibit gut motility. This finding would provide more evidence for the application of this yeast probiotic in IBS and other diarrheal disorders.}, }
@article {pmid35689247, year = {2022}, author = {Vaitkute, G and Panic, G and Alber, DG and Faizura-Yeop, I and Cloutman-Green, E and Swann, J and Veys, P and Standing, JF and Klein, N and Bajaj-Elliott, M}, title = {Linking gastrointestinal microbiota and metabolome dynamics to clinical outcomes in paediatric haematopoietic stem cell transplantation.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {89}, pmid = {35689247}, issn = {2049-2618}, support = {MR/M008665/1/MRC_/Medical Research Council/United Kingdom ; MR/N006321/1/MRC_/Medical Research Council/United Kingdom ; M008665/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Child ; Clostridiales ; Enterobacteriaceae ; Feces ; *Gastrointestinal Microbiome ; *Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Metabolome ; Viremia/etiology ; }, abstract = {BACKGROUND: Haematopoietic stem cell transplantation is a curative procedure for a variety of conditions. Despite major advances, a plethora of adverse clinical outcomes can develop post-transplantation including graft-versus-host disease and infections, which remain the major causes of morbidity and mortality. There is increasing evidence that the gastrointestinal microbiota is associated with clinical outcomes post-haematopoietic stem cell transplantation. Herein, we investigated the longitudinal dynamics of the gut microbiota and metabolome and potential associations to clinical outcomes in paediatric haematopoietic stem cell transplantation at a single centre.<br><br>RESULTS: On admission (baseline), the majority of patients presented with a different gut microbial composition in comparison with healthy control children with a significantly lower alpha diversity. A further, marked decrease in alpha diversity was observed immediately post-transplantation and in most microbial diversity, and composition did not return to baseline status whilst hospitalised. Longitudinal trajectories identified continuous fluctuations in microbial composition, with the dominance of a single taxon in a significant proportion of patients. Using pam clustering, three clusters were observed in the dataset. Cluster 1 was common pre-transplantation, characterised by a higher abundance of Clostridium XIVa, Bacteroides and Lachnospiraceae; cluster 2 and cluster 3 were more common post-transplantation with a higher abundance of Streptococcus and Staphylococcus in the former whilst Enterococcus, Enterobacteriaceae and Escherichia predominated in the latter. Cluster 3 was also associated with a higher risk of viraemia. Likewise, further multivariate analysis reveals Enterobacteriaceae, viraemia, use of total parenteral nutrition and various antimicrobials contributing towards cluster 3, Streptococcaceae, Staphylococcaceae, Neisseriaceae, vancomycin and metronidazole contributing towards cluster 2. Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae and not being on total parenteral nutrition contributed to cluster 1. Untargeted metabolomic analyses revealed changes that paralleled fluctuations in microbiota composition; importantly, low faecal butyrate was associated with a higher risk of viraemia.<br><br>CONCLUSIONS: These findings highlight the frequent shifts and dominations in the gut microbiota of paediatric patients undergoing haematopoietic stem cell transplantation. The study reveals associations between the faecal microbiota, metabolome and viraemia. To identify and explore the potential of microbial biomarkers that may predict the risk of complications post-HSCT, larger multi-centre studies investigating the longitudinal microbial profiling in paediatric haematopoietic stem cell transplantation are warranted. Video abstract.}, }
@article {pmid35688268, year = {2022}, author = {Zhang, KK and Liu, JL and Chen, LJ and Li, JH and Yang, JZ and Xu, LL and Chen, YK and Zhang, QY and Li, XW and Liu, Y and Zhao, D and Xie, XL and Wang, Q}, title = {Gut microbiota mediates methamphetamine-induced hepatic inflammation via the impairment of bile acid homeostasis.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {166}, number = {}, pages = {113208}, doi = {10.1016/j.fct.2022.113208}, pmid = {35688268}, issn = {1873-6351}, mesh = {Animals ; Bile Acids and Salts/metabolism ; *Chemical and Drug Induced Liver Injury/metabolism ; *Gastrointestinal Microbiome ; Homeostasis ; Inflammation/drug therapy ; Liver ; *Methamphetamine/toxicity ; Mice ; Mice, Inbred C57BL ; Myeloid Differentiation Factor 88/genetics/metabolism ; NF-kappa B/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Toll-Like Receptor 4/metabolism ; }, abstract = {Methamphetamine (Meth), an addictive psychostimulant of abuse worldwide, has been a common cause of acute toxic hepatitis in adults. Gut microbiota has emerged as a modulator of host immunity via metabolic pathways. However, the microbial mechanism of Meth-induced hepatic inflammation and effective therapeutic strategies remain unknown. Here, mice were intraperitoneally (i.p.) injected with Meth to induce hepatotoxicity. Cecal microbiome and bile acids (BAs) composition were analyzed after Meth administration. Fecal microbiota transplantation (FMT) technology was utilized to investigate the role of microbiota. Additionally, the protective effects of obeticholic acid (OCA), an agonist of farnesoid X receptor (FXR), were evaluated. Results indicated that Meth administration induced hepatic cholestasis, dysfunction and aroused hepatic inflammation by stimulating the TLR4/MyD88/NF-κB pathway in mice. Meanwhile, Meth disturbed the cecal microbiome and impaired the homeostasis of BAs. Interestingly, FMT from Meth administered mice resulted in serum and hepatic BA accumulation and transferred similar phenotypic changes into the healthy recipient mice. Finally, OCA normalized Meth-induced BA accumulation in both serum and the liver, and effectively protected against Meth-induced hepatic dysfunction and inflammation by suppressing the TLR4/MyD88/NF-κB pathway. This study established the importance of microbial mechanism and its inhibition as a potential therapeutic target to treat Meth-related hepatotoxicity.}, }
@article {pmid35681702, year = {2022}, author = {Sampsell, K and Wang, W and Ohland, C and Mager, LF and Pett, N and Lowry, DE and Sales, KM and McNeely, ML and McCoy, KD and Culos-Reed, SN and Reimer, RA}, title = {Exercise and Prebiotic Fiber Provide Gut Microbiota-Driven Benefit in a Survivor to Germ-Free Mouse Translational Model of Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {11}, pages = {}, pmid = {35681702}, issn = {2072-6694}, support = {VPR Catalyst Grant//University of Calgary/ ; Cancer Prevention Research Opportunity//Alberta Innovates/ ; Grant//Alberta Cancer Foundation/ ; }, abstract = {The gut microbiota plays a role in shaping overall host health and response to several cancer treatments. Factors, such as diet, exercise, and chemotherapy, can alter the gut microbiota. In the present study, the Alberta Cancer Exercise (ACE) program was investigated as a strategy to favorably modify the gut microbiota of breast cancer survivors who had received chemotherapy. Subsequently, the ability of post-exercise gut microbiota, alone or with prebiotic fiber supplementation, to influence breast cancer outcomes was interrogated using fecal microbiota transplant (FMT) in germ-free mice. While cancer survivors experienced little gut microbial change following ACE, in the mice, tumor volume trended consistently lower over time in mice colonized with post-exercise compared to pre-exercise microbiota with significant differences on days 16 and 22. Beta diversity analysis revealed that EO771 breast tumor cell injection and Paclitaxel chemotherapy altered the gut microbial communities in mice. Enrichment of potentially protective microbes was found in post-exercise microbiota groups. Tumors of mice colonized with post-exercise microbiota exhibited more favorable cytokine profiles, including decreased vascular endothelial growth factor (VEGF) levels. Beneficial microbial and molecular outcomes were augmented with prebiotic supplementation. Exercise and prebiotic fiber demonstrated adjuvant action, potentially via an enhanced anti-tumor immune response modulated by advantageous gut microbial shifts.}, }
@article {pmid35681546, year = {2022}, author = {Huang, C and Mei, Q and Lou, L and Huang, Z and Fu, Y and Fan, J and Wang, J and Yin, N and Zheng, Y and Lu, Y and Zeng, Y}, title = {Ulcerative Colitis in Response to Fecal Microbiota Transplantation via Modulation of Gut Microbiota and Th17/Treg Cell Balance.}, journal = {Cells}, volume = {11}, number = {11}, pages = {}, pmid = {35681546}, issn = {2073-4409}, mesh = {*Colitis, Ulcerative/pathology ; Fecal Microbiota Transplantation ; Forkhead Transcription Factors ; *Gastrointestinal Microbiome ; Humans ; Leukocyte L1 Antigen Complex/pharmacology ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics ; RNA, Ribosomal, 16S ; T-Lymphocytes, Regulatory/pathology ; *Transcription Factors ; }, abstract = {Background: Fecal microbiota transplantation (FMT) may contribute to disease remission in ulcerative colitis (UC). We studied the microbiota change and its regulation on T cells after FMT. Methods: Patients with mild to moderately active UC were included to receive FMT. The intestinal histopathological changes and barrier function were evaluated. The fecal samples of donors and patients were analyzed by 16S rRNA gene-based microbiota analysis, and the colon Th17 and Treg cells were assessed. Results: Fifteen patients completed the 8-week-follow-up. A total of 10 patients (66.7%) were in the responders (RE) group and five in the non-responders (NR) group. The Nancy histological index and fecal calprotectin decreased (p < 0.001, p = 0.06, respectively) and Occludin and Claudin1 increased in the RE group. The abundance of Faecalibaterium increased significantly by 2.3-fold in the RE group at week 8 (p = 0.043), but it was suppressed in the NR group. Fecal calprotectin (r = −0.382, p = 0.003) and Nancy index (r = −0.497, p = 0.006) were correlated inversely with the abundance of Faecalibacterium, respectively. In the RE group the relative mRNA expression of RORγt decreased and Foxp3 increased. Significantly decreased CD4+ RORγt+ Th17 and increased CD4+ Foxp3+ Treg were also observed in the RE group. The relative abundance of Faecalibacterium correlated with CD4+ RORγt+ Th17 (r = −0.430, p = 0.018) and CD4+ Foxp3+ Treg (r = 0.571, p = 0.001). Conclusions: The long-term Faecalibaterium colonization following FMT plays a crucial role in UC remission by alleviating intestinal inflammation. This anti-inflammatory effect of Faecalibacterium may be achieved by regulating the imbalance of Th17/Treg levels in UC.}, }
@article {pmid35680942, year = {2022}, author = {Hui, Y and Vestergaard, G and Deng, L and Kot, WP and Thymann, T and Brunse, A and Nielsen, DS}, title = {Donor-dependent fecal microbiota transplantation efficacy against necrotizing enterocolitis in preterm pigs.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {48}, pmid = {35680942}, issn = {2055-5008}, mesh = {Animals ; *Enterocolitis, Necrotizing/prevention &amp; control/veterinary ; *Fecal Microbiota Transplantation ; Follow-Up Studies ; Humans ; Infant, Newborn ; Infant, Premature ; Phylogeny ; Swine ; }, abstract = {The development of necrotizing enterocolitis (NEC), a life-threatening inflammatory bowel disease affecting preterm infants, is connected with gut microbiota dysbiosis. Using preterm piglets as a model for preterm infants we recently showed that fecal microbiota transplantation (FMT) from healthy suckling piglet donors to newborn preterm piglets decreased the NEC risk. However, in a follow-up study using donor stool from piglets recruited from another farm, this finding could not be replicated. This allowed us to study donor-recipient microbiota dynamics in a controlled model system with a clear difference in NEC phenotype. Preterm piglets (n = 38) were randomly allocated to receive control saline (CON), or rectal FMT using either the ineffective (FMT1) or the effective donor stool (FMT2). All animals were followed for four days before necropsy and gut pathological evaluation. Donor and recipient colonic gut microbiota (GM) were analyzed by 16 S rRNA gene amplicon sequencing and shotgun metagenomics. As expected, only FMT2 recipients were protected against NEC. Both FMT groups had shifted GM composition relative to CON, but FMT2 recipients had a higher lactobacilli relative abundance compared to FMT1. Limosilactobacillus reuteri and Lactobacillus crispatus strains of FMT recipients showed high phylogenetic similarity with their respective donors, indicating engraftment. Moreover, the FMT2 group had a higher lactobacilli replication rate and harbored specific glycosaminoglycan-degrading Bacteroides. In conclusion, subtle species-level donor differences translate to major changes in engraftment dynamics and the ability to prevent NEC. This could have implications for proper donor selection in future FMT trials for NEC prevention.}, }
@article {pmid35680592, year = {2022}, author = {Tang, XW and Wu, DP}, title = {[How I treat gastrointestinal tract acute graft versus host disease with fecal microbiota transplantation].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {43}, number = {5}, pages = {365-369}, pmid = {35680592}, issn = {0253-2727}, mesh = {Acute Disease ; Fecal Microbiota Transplantation ; Gastrointestinal Tract ; *Graft vs Host Disease/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; }, }
@article {pmid35675471, year = {2024}, author = {Wang, Y and Yang, Z and Tang, H and Sun, X and Qu, J and Lu, S and Rao, B}, title = {Faecal microbiota transplantation is better than probiotics for tissue regeneration of type 2 diabetes mellitus injuries in mice.}, journal = {Archives of physiology and biochemistry}, volume = {130}, number = {3}, pages = {333-341}, doi = {10.1080/13813455.2022.2080229}, pmid = {35675471}, issn = {1744-4160}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; *Diabetes Mellitus, Type 2/therapy/complications/microbiology ; Mice ; Male ; *Regeneration ; *Diabetes Mellitus, Experimental/therapy/complications ; *Lactobacillus ; Bifidobacterium ; Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Insulin-Secreting Cells/metabolism ; Blood Glucose/metabolism ; Insulin Resistance ; }, abstract = {CONTEXT: Western diet and unhealthy lifestyle have contributed to the continued growth of type 2 diabetes mellitus (T2DM). T2DM is associated with dysbacteriosis, and studies have found that altering the gut microbiota has a positive effect on treatment.<br><br>OBJECTIVE: In addition to hyperglycaemia, T2DM often causes damage to multiple organs. However, there are few studies on organ damage from faecal microbiota transplantation (FMT).<br><br>MATERIALS AND METHODS: T2DM mice were divided into four groups and were given phosphate buffered saline (PBS) (T2DM group), FMT (FMT group), Lactobacillus (LAB group), and Bifidobacterium (BIO group) by gavage for six&#x2009;weeks, respectively. Mice on a normal diet (control group) were gavaged with PBS for six&#x2009;weeks.<br><br>RESULTS: After gavage treatment, FMT, LAB, and BIO groups were similar in lowering glucose, endotoxemia was slightly reduced, and the colonic mucus layer and liver lobules developed towards normal tissue. Surprisingly, we found that the FMT group had unique effects on islet cell regeneration, increased functional &#x3b2; cells, and insulin sensitivity.<br><br>DISCUSSION AND CONCLUSION: Lactobacillus has the best glucose-lowering effect, but FMT has obvious advantages in &#x3b2;-cell regeneration, which provides new treatment ideas for tissue damage caused by T2DM.}, }
@article {pmid35672382, year = {2022}, author = {Bose, D and Chatterjee, S and Older, E and Seth, R and Janulewicz, P and Saha, P and Mondal, A and Carlson, JM and Decho, AW and Sullivan, K and Klimas, N and Lasley, S and Li, J and Chatterjee, S}, title = {Host gut resistome in Gulf War chronic multisymptom illness correlates with persistent inflammation.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {552}, pmid = {35672382}, issn = {2399-3642}, support = {I01 CX001923/CX/CSRD VA/United States ; }, mesh = {Aged ; Chronic Disease ; *Gulf War ; Humans ; Inflammation/genetics ; *Veterans ; }, abstract = {Chronic multisymptom illness (CMI) affects a subsection of elderly and war Veterans and is associated with systemic inflammation. Here, using a mouse model of CMI and a group of Gulf War (GW) Veterans' with CMI we show the presence of an altered host resistome. Results show that antibiotic resistance genes (ARGs) are significantly altered in the CMI group in both mice and GW Veterans when compared to control. Fecal samples from GW Veterans with persistent CMI show a significant increase of resistance to a wide class of antibiotics and exhibited an array of mobile genetic elements (MGEs) distinct from normal healthy controls. The altered resistome and gene signature is correlated with mouse serum IL-6 levels. Altered resistome in mice also is correlated strongly with intestinal inflammation, decreased synaptic plasticity, reversible with fecal microbiota transplant (FMT). The results reported might help in understanding the risks to treating hospital acquired infections in this population.}, }
@article {pmid35668615, year = {2023}, author = {Teng, T and Sun, G and Song, X and Shi, B}, title = {The early faecal microbiota transfer alters bile acid circulation and amino acid transport of the small intestine in piglets.}, journal = {Journal of animal physiology and animal nutrition}, volume = {107}, number = {2}, pages = {564-573}, doi = {10.1111/jpn.13739}, pmid = {35668615}, issn = {1439-0396}, support = {JQ2019C002//Natural Science Fund for Distinguished Young Scholars of Heilongjiang Province of China/ ; }, mesh = {Swine ; Animals ; Female ; *Fecal Microbiota Transplantation/veterinary ; *Bile Acids and Salts ; Intestine, Small ; Amino Acids ; Immunoglobulin A ; }, abstract = {The purpose of this study was to investigate the effects of faecal microbiota transfer (FMT) with lactation Min sows as faecal donor on blood immunity, small intestine amino acid transport capacity, bile acid circulation, and colon microbiota of recipient piglets. From Days 1 to 10, the recipient group (R group) was orally inoculated with a faecal suspension. The control group (Con group) was orally inoculated with sterile physiological saline. On Day 21, the results showed that the immunoglobulin A (IgA) concentration in plasma of the R group was increased (p < 0.05). The expression of 4F2hc in the jejunal mucosa and ileum mucosa of the R group was ameliorated (p < 0.05). The relative abundance of Synergistetes in the colon of the R group was increased, Proteobacteria was diminished by FMT (p < 0.05). On Day 40, the concentrations of IgA, IgG, and interleukin-2 detected in the plasma of the R group were increased (p < 0.05). FXR and fibroblast growth factor 19 gene expression was upregulated in ileum mucosa, CYP7A1 and Na[+] taurocholate cotransporter polypeptide gene expression were downregulated in the liver and organic solute transporters α/β was downregulated in colonic mucosa (p < 0.05). The relative abundance of Proteobacteria and Spirochaetes in the colon of the R group was decreased (p < 0.05). In conclusion, an early FMT with lactation Min sows as faecal donors can alter the small intestine amino acid transport capacity, bile acid circulation, and colonic microbiota of recipient piglets during lactation and after weaning.}, }
@article {pmid35665355, year = {2022}, author = {Chen, Y and Zhiliang, L and Jiaqu, C and Xiaoqiong, L and Shaoyi, Z and Chunlian, M and Yinmei, Y and Bo, Y and Di, Z and Hongliang, T and Ning, L and Qiyi, C and Huanlong, Q}, title = {Fecal Microbiota and Human Intestinal Fluid Transplantation: Methodologies and Outlook.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {830004}, pmid = {35665355}, issn = {2296-858X}, abstract = {Fecal microbiota transplantation (FMT) is a therapy that involves the transplantation of healthy human fecal microorganisms into the gut of patients to rebuild or consolidate the intestinal microecology. It has been utilized in many diseases. However, FMT had a limited effect on patients with small intestinal diseases because of the unique ecological characteristics of the microorganisms. Thus, we proposed a new microecology transplantation therapy called human intestinal fluid transplantation (HIFT). Human intestinal fluid can be collected through a nasojejunal tube and be made into capsules using the freeze-dried powder method. In addition, strict standards for donor screening and management have been established. We are currently developing a high-standard HIFT preparation system and conducting high-quality clinical studies to validate the safety and efficacy of HIFT combined with FMT.}, }
@article {pmid35664229, year = {2022}, author = {Li, M and Yang, L and Mu, C and Sun, Y and Gu, Y and Chen, D and Liu, T and Cao, H}, title = {Gut microbial metabolome in inflammatory bowel disease: From association to therapeutic perspectives.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {2402-2414}, pmid = {35664229}, issn = {2001-0370}, abstract = {Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a set of clinically chronic, relapsing gastrointestinal inflammatory disease and lacks of an absolute cure. Although the precise etiology is unknown, developments in high-throughput microbial genomic sequencing significantly illuminate the changes in the intestinal microbial structure and functions in patients with IBD. The application of microbial metabolomics suggests that the microbiota can influence IBD pathogenesis by producing metabolites, which are implicated as crucial mediators of host-microbial crosstalk. This review aims to elaborate the current knowledge of perturbations of the microbiome-metabolome interface in IBD with description of altered composition and metabolite profiles of gut microbiota. We emphasized and elaborated recent findings of several potentially protective metabolite classes in IBD, including fatty acids, amino acids and derivatives and bile acids. This article will facilitate a deeper understanding of the new therapeutic approach for IBD by applying metabolome-based adjunctive treatment.}, }
@article {pmid35664001, year = {2022}, author = {Liu, P and Zhou, X and Zhang, H and Wang, R and Wu, X and Jian, W and Li, W and Yuan, D and Wang, Q and Zhao, W}, title = {Danggui-Shaoyao-San Attenuates Cognitive Impairment via the Microbiota-Gut-Brain Axis With Regulation of Lipid Metabolism in Scopolamine-Induced Amnesia.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {796542}, pmid = {35664001}, issn = {1664-3224}, mesh = {Amnesia/chemically induced/drug therapy ; Animals ; Brain-Gut Axis ; *Cognitive Dysfunction/drug therapy ; Drugs, Chinese Herbal ; Lipid Metabolism ; Mice ; Mice, Inbred C57BL ; *Microbiota ; RNA, Ribosomal, 16S ; Scopolamine/adverse effects ; }, abstract = {Danggui-Shaoyao-San (DSS) has a long history of being used as a traditional medicine (TCM) and has been reported to show therapeutic effects in alleviating the symptoms of cognitive impairment. The purpose of this study was to investigate whether DSS treatment attenuates cognitive impairment via the microbiota-gut-brain axis in scopolamine-induced amnesia. In this work, we first performed the Morris water maze (MWM) test and novel object recognition (NOR) test to evaluate the memory function of treated C57BL/6N mice. Then we evaluated 16S rRNA for gut microbiota analysis, as well as assessment of blood-brain barrier function and intestinal barrier function and lipid metabolism analysis on tissues from different groups. We hypothesised that DSS may affect brain function and behavior through the gut-brain axis in a bidirectional interplay with both top-down and bottom-up regulation. Furthermore, in order to confirm whether intestinal flora plays a crucial role in scopolamine-induced amnesia, C57BL/6N mice were treated with fecal microbial transplantation (FMT), and then behavioral tests were performed. The mice's feces were simultaneously evaluated by 16S rRNA analysis. The result supported that the FMT-induced improvement in cognitive function highlights the role of the gut microbiota-brain axis to mediate cognitive function and behavior. Besides theses works, more findings indicated that DSS altered lipid metabolism by activating LXR-PPAR-γ and repaired mucosal barrier dysfunction assessed with a broad range of techniques, which attenuated cognitive impairment via the microbiota-gut-brain axis.}, }
@article {pmid35662937, year = {2022}, author = {You, H and Tan, Y and Yu, D and Qiu, S and Bai, Y and He, J and Cao, H and Che, Q and Guo, J and Su, Z}, title = {The Therapeutic Effect of SCFA-Mediated Regulation of the Intestinal Environment on Obesity.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {886902}, pmid = {35662937}, issn = {2296-861X}, abstract = {Intestinal environment disorder is a potential pathological mechanism of obesity. There is increasing evidence that disorders in the homeostasis of the intestinal environment can affect various metabolic organs, such as fat and liver, and lead to metabolic diseases. However, there are few therapeutic approaches for obesity targeting the intestinal environment. In this review, on the one hand, we discuss how intestinal microbial metabolites SCFA regulate intestinal function to improve obesity and the possible mechanisms and pathways related to obesity-related pathological processes (depending on SCFA-related receptors such as GPCRs, MCT and SMCT, and through epigenetic processes). On the other hand, we discuss dietary management strategies to enrich SCFA-producing bacteria and target specific SCFA-producing bacteria and whether fecal bacteria transplantation therapy to restore the composition of the gut microbiota to regulate SCFA can help prevent or improve obesity. Finally, we believe that it will be of great significance to establish a working model of gut- SCFA- metabolic disease development in the future for the improvement this human health concern.}, }
@article {pmid35660786, year = {2022}, author = {Rees, NP and Shaheen, W and Quince, C and Tselepis, C and Horniblow, RD and Sharma, N and Beggs, AD and Iqbal, TH and Quraishi, MN}, title = {Systematic review of donor and recipient predictive biomarkers of response to faecal microbiota transplantation in patients with ulcerative colitis.}, journal = {EBioMedicine}, volume = {81}, number = {}, pages = {104088}, pmid = {35660786}, issn = {2352-3964}, mesh = {Biomarkers ; *Colitis, Ulcerative/diagnosis/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; Feces ; *Gastrointestinal Microbiome ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has previously been explored as a treatment for ulcerative colitis (UC) however, biomarkers that predict and / or are associated with clinical response are poorly defined. The aim of this systematic review was to identify donor and recipient clinical, microbial and metabolomic predictive biomarkers of response to FMT in UC.<br><br>METHODS: A systematic search of the relevant literature of studies exploring FMT in UC was conducted. Data on microbial diversity, taxonomic changes, metabolic changes, donor and recipient microbiota relationship and baseline predictors was examined.<br><br>FINDINGS: 2852 studies were screened, and 25 papers were included in this systematic review. Following FMT, alpha diversity was seen to increase in responders along with increases in the abundance of Clostridiales clusters (order) and Bacteroides genus. Metabolomic analysis revealed short chain fatty acid (SCFA) production as a marker of FMT success. Donors or FMT batches with higher microbial alpha diversity and a greater abundance of taxa belonging to certain Bacteroides and Clostridia clusters were associated with clinical response to FMT. Baseline clinical predictors of response in patients with UC included younger age, less severe disease and possibly shorter disease duration. Baseline recipient microbial predictors at response consisted of higher faecal species richness, greater abundance of Candida and donor microbial profile similarity.<br><br>INTERPRETATION: Distinct changes in gut microbiota profiles post-FMT indicate that certain baseline characteristics along with specific microbial and metabolomic alterations may predispose patients towards a successful therapeutic outcome. Opportunities towards a biomarker led precision medicine approach with FMT should be explored in future clinical studies.<br><br>FUNDING: There no specific funding to declare.}, }
@article {pmid35660380, year = {2022}, author = {Liu, M and Sun, B and Zhou, X and Chen, L}, title = {Disturbed glucose metabolism by perfluorobutanesulfonate pollutant and benefit of young fecal transplantation in aged zebrafish.}, journal = {Ecotoxicology and environmental safety}, volume = {241}, number = {}, pages = {113721}, doi = {10.1016/j.ecoenv.2022.113721}, pmid = {35660380}, issn = {1090-2414}, mesh = {Animals ; *Environmental Pollutants/metabolism ; Fecal Microbiota Transplantation ; Fluorocarbons ; Glucose/metabolism ; Liver ; Proteomics ; Sulfonic Acids ; *Water Pollutants, Chemical/toxicity ; Zebrafish/metabolism ; alpha-Amylases ; }, abstract = {Perfluorobutanesulfonate (PFBS) is an environmental pollutant of emerging concern, which significantly impacts the metabolism and health of animals. Because of the loss of functional capacity, the aged animals are regarded more susceptible to the toxicity of environmental pollutants. In the present study, aged zebrafish were employed as the toxicological animal and transplanted with the feces collected from young donors for 14 days, after which the acclimated elderly were exposed to PFBS at environmentally relevant concentrations (0 and 100 μg/L) for another 14 days. When the exposure was concluded, glucose metabolic disturbances of PFBS in the aged and efficacy of young fecal transplant to mitigate the toxicity of PFBS were explored along the gut-liver axis. The results showed that PFBS exposure significantly inhibited the enzymatic activity of α-amylase in the gut, but increased the alanine aminotransferase (ALT) activity in the blood of the aged zebrafish, suggesting the impairment of intestinal digestive functions of carbohydrates and the induction of liver damage by PFBS. However, young fecal transplantation successfully ameliorated the toxicity of PFBS on α-amylase and ALT, underlining the benefits conveyed to the health of the elderly. In addition, transplantation of young feces was efficient to alleviate the hyperglycemia symptom in the elderly via stimulating the secretion of insulin. PFBS exposure increased blood glucagon level, disrupted insulin receptor transcription, and depleted hepatic glycogen store, which were all mitigated by young fecal transplant. Hepatic proteomic analysis also found dynamic interactions between young fecal transplantation and PFBS pollutant on the metabolic pathways of glucose and glycogen, involving glycolysis, gluconeogenesis, glycogenesis, and glycogenolysis. Overall, the present findings highlighted the beneficial effects of young fecal transplantation to protect the aged from the glucose metabolism toxicity of PFBS, thus providing a plausible measure to improve the health aging status.}, }
@article {pmid35660350, year = {2022}, author = {Yan, S and Chang, J and Hao, X and Liu, J and Tan, X and Geng, Z and Wang, Z}, title = {Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {102}, number = {}, pages = {154217}, doi = {10.1016/j.phymed.2022.154217}, pmid = {35660350}, issn = {1618-095X}, mesh = {Animals ; Azoxymethane ; *Berberine/pharmacology ; Carcinogenesis ; Cell Transformation, Neoplastic ; *Colitis/chemically induced/complications/drug therapy ; *Colorectal Neoplasms/drug therapy/metabolism ; Dextran Sulfate ; Disease Models, Animal ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome ; Interleukin-6/metabolism ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Occludin ; Tandem Mass Spectrometry ; Toll-Like Receptor 4 ; }, abstract = {BACKGROUND: Colitis-associated cancer (CAC) is known to be a complex combination of tumor cells, non-tumor cells and a large intestinal flora. The increasing role of intestinal flora in CAC may represent a new approach to improving CAC treatment. Berberine can reduce colorectal adenoma recurrence and inhibit colorectal carcinogenesis.<br><br>PURPOSE: Berberine has demonstrated efficacy for the control and suppression of CAC. Given the low oral absorption into the blood and large intestinal excretion of berberine, intestinal flora may be one of the important targets of berberine inhibiting the occurrence of colorectal cancer (CRC). The purpose of this study was to investigate the effects of berberine on intestinal flora in CAC mice and its ability to remodel intestinal flora to improve short-chain fatty acid metabolism.<br><br>STUDY DESIGN AND METHODS: The CAC model in mice was induced by Azoxymethane/Dextran sodium sulfate (AOM/DSS). Berberine was administered daily at doses of 50 and 100&#xa0;mg/kg, and aspirin was used as the positive control. The effect of berberine on colitis-associated colorectal tumorigenesis was assessed by general imaging, tumor counting, and Ki67 staining. Intestinal flora changes were detected by 16S rDNA sequencing technology. Targeted short-chain fatty acid detection was performed by GC-MS/MS, and Lipopolysaccharide (LPS) levels in feces were quantified with an ELISA kit. The signaling pathway of TLR4/NF-&#x3ba;B P65/IL-6/p-STAT3 was evaluated by Western blotting and immunofluorescence. The expression levels of intestinal barrier functional biomarkers Occludin and ZO-1 were detected by immunohistochemistry. Fecal flora transplantation (FMT) was used to evaluate the effect of intestinal flora in inhibiting inflammatory cancer transformation by berberine.<br><br>RESULTS: Berberine reduced the number and load of tumors in CAC mice. Berberine remodeled the composition of pathogenic and beneficial bacteria in mice with colitis-associated colorectal tumorigenesis. Berberine treatment resulted in increases in fecal butyric acid, acetic acid and propionic acid levels, but did not alter isobutyric acid, isovaleric acid, valeric acid and caproic acid. In addition, berberine reduced LPS content in feces in mice with colitis-associated colorectal tumorigenesis. Occludin and ZO-1 were upregulated, and the TLR4/p-NF-&#x3ba;B p65/IL-6/p-STAT3 inflammatory-cancer transformation pathway was inhibited with berberine. The FMT results further verified that the berberine-treated intestinal flora was sufficient to alleviate the occurrence of colonic tumors associated with colitis in mice.<br><br>CONCLUSION: Our study showed that berberine alleviated the colitis-associated colorectal tumorigenesis from three equilibrium levels: (1) Pathogenic and beneficial bacteria; (2) Short-chain fatty acids and LPS produced by intestinal flora; and (3) Inflammatory cancer transformation signaling and intestinal barrier function. This study provided a new approach and experimental basis for the application of berberine in the treatment of CAC in clinical practice.}, }
@article {pmid35658593, year = {2022}, author = {Fang, H and Fang, M and Wang, Y and Zhang, H and Li, J and Chen, J and Wu, Q and He, L and Xu, J and Deng, J and Liu, M and Deng, Y and Chen, C}, title = {Indole-3-Propionic Acid as a Potential Therapeutic Agent for Sepsis-Induced Gut Microbiota Disturbance.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0012522}, pmid = {35658593}, issn = {2165-0497}, mesh = {Animals ; Dysbiosis/therapy ; *Gastrointestinal Microbiome/physiology ; Indoles/metabolism/pharmacology ; Mice ; Propionates ; *Sepsis/drug therapy ; }, abstract = {The effects of using gut microbiota metabolites instead of live microorganisms to modulate sepsis-induced gut dysbiosis remain largely unknown. We assessed the effects of microbiota metabolite indole-3-propionic acid (IPA) on gut microbiota in mice during sepsis. Sepsis models were constructed by cecal ligation and puncture (CLP) methods. Fecal microbiota composition analysis was performed to characterize the gut microbiota composition. Fecal microbiota transplantation was performed to validate the roles of gut microbiota on sepsis progression. IPA-treated mice exhibited lower serum inflammatory mediator levels and a higher survival rate than those of saline-treated mice after modeling of sepsis, which were negated in the presence of antibiotics. Compared with saline-treated mice after modeling, IPA-treated mice showed a markedly different intestinal microbiota composition, with an enrichment of Bifidobacteriaceae family and a depletion of Enterobacteriaceae family. Mice gavaged with postoperative feces from IPA-treated animals displayed better survival than mice gavaged with feces from saline-treated animals. Overall, these data suggest that IPA offers a microbe-modulated survival advantage in septic mice, indicating that some microbiota metabolites could replace live microorganisms as potential options for regulation of sepsis-induced gut dysbiosis. IMPORTANCE The role of gut microbiota in the pathophysiology of sepsis is gaining increasing attention and developing effective and safe sepsis therapies targeting intestinal microorganisms is promising. Given the safety of probiotic supplementation or fecal microbiota transplantation in critically ill patients, identifying an abiotic agent to regulate the intestinal microbiota of septic patients is of clinical significance. This study revealed that IPA, a microbiota-generated tryptophan metabolite, ameliorated sepsis-induced mortality and decreased the serum levels of proinflammatory cytokines by modulating intestinal microbiota. Although IPA did not increase the abundance and diversity of the microbiota of septic mice, it significantly decreased the number of Enterobacteriaceae family. These findings indicate that a specific microbiota metabolite (e.g., IPA) can mediate the intestinal microbiota apart from FMT or probiotics.}, }
@article {pmid35655344, year = {2022}, author = {Zhang, ZJ and Lehmann, CJ and Cole, CG and Pamer, EG}, title = {Translating Microbiome Research From and To the Clinic.}, journal = {Annual review of microbiology}, volume = {76}, number = {}, pages = {435-460}, doi = {10.1146/annurev-micro-041020-022206}, pmid = {35655344}, issn = {1545-3251}, support = {R01 AI095706/AI/NIAID NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; }, mesh = {*Disease ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Probiotics/therapeutic use ; *Therapeutics/trends ; }, abstract = {Extensive research has elucidated the influence of the gut microbiota on human health and disease susceptibility and resistance. We review recent clinical and laboratory-based experimental studies associating the gut microbiota with certain human diseases. We also highlight ongoing translational advances that manipulate the gut microbiota to treat human diseases and discuss opportunities and challenges in translating microbiome research from and to the bedside.}, }
@article {pmid35654877, year = {2022}, author = {Stockdale, SR and Harrington, RS and Shkoporov, AN and Khokhlova, EV and Daly, KM and McDonnell, SA and O'Reagan, O and Nolan, JA and Sheehan, D and Lavelle, A and Draper, LA and Shanahan, F and Ross, RP and Hill, C}, title = {Metagenomic assembled plasmids of the human microbiome vary across disease cohorts.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {9212}, pmid = {35654877}, issn = {2045-2322}, mesh = {Humans ; *Inflammatory Bowel Diseases/genetics/microbiology ; Metagenome ; Metagenomics ; *Microbiota ; Plasmids/genetics ; }, abstract = {We compiled a human metagenome assembled plasmid (MAP) database and interrogated differences across multiple studies that were originally designed to investigate the composition of the human microbiome across various lifestyles, life stages and events. This was performed as plasmids enable bacteria to rapidly expand their functional capacity through mobilisation, yet their contribution to human health and disease is poorly understood. We observed that inter-sample β-diversity differences of plasmid content (plasmidome) could distinguish cohorts across a multitude of conditions. We also show that reduced intra-sample plasmidome α-diversity is consistent amongst patients with inflammatory bowel disease (IBD) and Clostridioides difficile infections. We also show that faecal microbiota transplants can restore plasmidome diversity. Overall plasmidome diversity, specific plasmids, and plasmid-encoded functions can all potentially act as biomarkers of IBD or its severity. The human plasmidome is an overlooked facet of the microbiome and should be integrated into investigations regarding the role of the microbiome in promoting health or disease. Including MAP databases in analyses will enable a greater understanding of the roles of plasmid-encoded functions within the gut microbiome and will inform future human metagenome analyses.}, }
@article {pmid35654347, year = {2022}, author = {Xu, L and Zhang, Q and Dou, X and Wang, Y and Wang, J and Zhou, Y and Liu, X and Li, J}, title = {Fecal microbiota transplantation from young donor mice improves ovarian function in aged mice.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {49}, number = {11}, pages = {1042-1052}, doi = {10.1016/j.jgg.2022.05.006}, pmid = {35654347}, issn = {1673-8527}, mesh = {Female ; Animals ; Mice ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Cytokines ; Aging ; }, abstract = {Advanced maternal age is characterized by declines in the quantity and quality of oocytes in the ovaries, and the aging process is accompanied by changes in gut microbiota composition. However, little is known about the relationship between gut microbiota and ovarian aging. By using fecal microbiota transplantation (FMT) to transplant material from young (5-week-old) into aged (42-week-old) mice, we find that the composition of gut microbiota in FMT-treated mice presents a "younger-like phenotype" and an increase of commensal bacteria, such as Bifidobacterium and Ruminococcaceae. Moreover, the FMT-treated mice show increased anti-inflammatory cytokine IL-4 and decreased pro-inflammatory cytokine IFN-γ. Fertility tests for assessing ovarian function reveal that the first litter size of female FMT-treated mice is significantly higher than that of the non-FMT group. Morphology analysis demonstrates a dramatic decrease in follicle atresia and apoptosis as well as an increase in cellular proliferation in the ovaries of the FMT-treated mice. Our results also show that FMT improves the immune microenvironment in aged ovaries, with decreased macrophages and macrophage-derived multinucleated giant cells (MNGCs). These results suggest that FMT from young donors could be a good choice for delaying ovarian aging.}, }
@article {pmid35653887, year = {2022}, author = {Duan, S and Li, X and Fan, G and Liu, R}, title = {Targeting bile acid signaling for the treatment of liver diseases: From bench to bed.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {152}, number = {}, pages = {113154}, doi = {10.1016/j.biopha.2022.113154}, pmid = {35653887}, issn = {1950-6007}, mesh = {Bile Acids and Salts/metabolism ; *Enterohepatic Circulation ; Humans ; Liver ; *Liver Diseases/drug therapy/metabolism ; Signal Transduction ; }, abstract = {Liver diseases and related complications have become one of the leading causes of morbidity and mortality worldwide, yet effective medicine or approved treatment approach is still limited. Thus, novel therapy is urgently required to prevent or at least slow down the growing burden of liver transplantation or even death caused by malignant liver diseases. As the irreplaceable modulator of hepatic and intestinal signaling cascades, bile acids (BAs) play complex physiological as well as pathological roles in regulating energy and immune homeostasis in various liver diseases, including but not limited to metabolic diseases and cholangiopathies, making them highly attractive therapeutic targets. In the current review, recent progress in the research of enterohepatic circulation of BAs and potential therapeutic targets of BAs signaling, especially the development of currently available treatments, including agonizts of FXR and TGR5, analogs of FGF19, inhibitors of ASBT, and the regulation of gut microbiome through fecal microbiota transplantation were extensively summarized. Their protective effects, molecular mechanisms, and outcomes of clinical trials were highlighted. The structural features of these candidates and perspectives for their future development were further discussed. In conclusion, we believe that pharmacological therapies targeting BAs signaling represent promising and efficient strategies for the treatment of complex and multifactorial liver disorders.}, }
@article {pmid35650202, year = {2022}, author = {Pu, Y and Zhang, Q and Tang, Z and Lu, C and Wu, L and Zhong, Y and Chen, Y and Hashimoto, K and Luo, Y and Liu, Y}, title = {Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation.}, journal = {Translational psychiatry}, volume = {12}, number = {1}, pages = {223}, pmid = {35650202}, issn = {2158-3188}, mesh = {Animals ; *Arthritis, Rheumatoid ; Cytokines/metabolism ; *Depression/etiology ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Interleukin-6 ; Mice ; *T-Lymphocytes/metabolism ; }, abstract = {Depression is common in patients with rheumatoid arthritis (RA); however, the precise mechanisms underlying a link between depression and RA remain unclear. Accumulating evidence suggests the role of gut-microbiota-brain axis in depression. In this study, we investigated whether collagen-induced arthritis (CIA) mice produce depression-like behaviors and abnormal composition of gut microbiota. Furthermore, we investigated whether fecal microbiota transplantation (FMT) from RA patients causes depression-like phenotypes in antibiotic cocktail (ABX)-treated mice. CIA mice displayed depression-like behaviors, increased blood levels of pro-inflammatory cytokine interleukin-6 (IL-6), decreased expression of synaptic proteins in the prefrontal cortex (PFC), and abnormal composition of gut microbiota. Furthermore, FMT from RA patients caused depression-like phenotypes, alterations of gut microbiota composition, increased levels of IL-6 and tumor necrosis factor-α (TNF-α), and downregulation of synaptic proteins in the PFC compared to FMT from healthy controls. There were correlations between relative abundance of microbiota and plasma cytokines, expression of synaptic proteins in the PFC or depression-like behaviors. Interestingly, FMT from RA patients induced T cells differentiation in Peyer's patches and spleen. Reduced percentage of Treg cells with an increase of Th1/Th2 index was observed in the mice after FMT from RA patients. These findings suggest that CIA mice exhibit depression-like behaviors, systemic inflammation, and abnormal composition of gut microbiota, and that FMT from RA patients produces depression-like behaviors in ABX-treated mice via T cells differentiation. Therefore, abnormalities in gut microbiota in RA patients may contribute to depression via gut-microbiota-brain axis.}, }
@article {pmid35647000, year = {2022}, author = {Zhi, W and Song, W and Abdi Saed, Y and Wang, Y and Li, Y}, title = {Fecal Capsule as a Therapeutic Strategy in IgA Nephropathy: A Brief Report.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {914250}, pmid = {35647000}, issn = {2296-858X}, abstract = {In this brief report, we reported an IgA nephropathy (IgAN) patient who presented in November 2020 with an acute exacerbation with massive proteinuria and diarrhea. He had the earliest onset in 2018 when his IgAN was diagnosed by renal biopsy. He has been treated with active ACEI/ARB drugs for more than 90 days, intermittent steroid therapy, combined with anti-infective therapy. Although his acute symptoms resolved with each episode, he became increasingly severe as the interval between episodes shortened. Accordingly, the immunosuppressive drugs were administered under the KDIGO guidelines and related guidelines. However, the patient and his family refused this treatment. We pondered over the possible pathogenesis of IgAN, and after a full discussion with the patient and his family, FMT was administered to him after obtaining his informed consent. During the FMT procedure, one healthy volunteer (the doctor himself) also took the FMT capsules. In the end, the patient's urine protein dropped significantly and even turned negative after treatment. Neither the patient nor the healthy volunteer experienced any serious adverse effects during the use of the capsules and the subsequent 6-month follow-up period. We also used metagenomic sequencing to analyze the intestinal flora of patients before and after treatment, and a gradual increase stood out in the abundance of the patient's intestinal flora after drug administration.}, }
@article {pmid35646285, year = {2022}, author = {Said, I and Ahad, H and Said, A}, title = {Gut microbiome in non-alcoholic fatty liver disease associated hepatocellular carcinoma: Current knowledge and potential for therapeutics.}, journal = {World journal of gastrointestinal oncology}, volume = {14}, number = {5}, pages = {947-958}, pmid = {35646285}, issn = {1948-5204}, abstract = {Metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). The gut microbiome is closely connected to the liver via the portal vein, and has recently been identified as a predictor of liver disease state. Studies in NAFLD, cirrhosis and HCC have identified certain microbial signatures associated with these diseases, with the disease-associated microbiome changes collectively referred to as dysbiosis. The pathophysiologic underpinnings of these observations are an area of ongoing investigation, with current evidence demonstrating that the gut microbiome can influence liver disease and carcinogenesis via effects on intestinal permeability (leaky gut) and activation of the innate immune system. In the innate immune system, pathogen recognition receptors (Toll like receptors) on resident liver cells and macrophages cause liver inflammation, fibrosis, hepatocyte proliferation and reduced antitumor immunity, leading to chronic liver disease and carcinogenesis. Dysbiosis-associated changes include increase in secondary bile acids and reduced expression of FXR (nuclear receptor), which have also been associated with deleterious effects on lipid and carbohydrate metabolism associated with progressive liver disease. Longitudinal experimental and clinical studies are needed in different populations to examine these questions further. The role of therapeutics that modulate the microbiome is an emerging field with experimental studies showing the potential of diet, probiotics, fecal microbiota transplantation and prebiotics in improving liver disease in experimental models. Clinical studies are ongoing with preliminary evidence showing improvement in liver enzymes and steatosis. The microbial profile is different in responders to cancer immunotherapy including liver cancer, but whether or not manipulation of the microbiome can be utilized to affect response is being investigated.}, }
@article {pmid35646276, year = {2022}, author = {Hoilat, GJ and Suhail, FK and Adhami, T and John, S}, title = {Evidence-based approach to management of hepatic encephalopathy in adults.}, journal = {World journal of hepatology}, volume = {14}, number = {4}, pages = {670-681}, pmid = {35646276}, issn = {1948-5182}, abstract = {Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function and represents one of the many complications of portal hypertension and decompensated liver disease. Although ammonia is clearly implicated in the pathogenesis of HE, the pathogenesis of HE is multifactorial with numerous mechanisms that results in functional impairment of neuronal cells. The initial management of HE focuses on supportive care and stabilization which includes providing appropriate nutritional support. Thereafter, focus should be on identifying and treating the precipitating factors. There are many therapeutic agents available for the management of HE, most of which are directed towards lowering the gut nitrogen load and thus the serum ammonia level. This review aims to provide an update on the conventional and emerging treatment options for HE.}, }
@article {pmid35645020, year = {2022}, author = {Topa, M and Sanders, DS and Elli, L}, title = {Biomarkers for the diagnosis and monitoring of celiac disease: can you count on me?.}, journal = {Current opinion in gastroenterology}, volume = {38}, number = {3}, pages = {263-269}, doi = {10.1097/MOG.0000000000000825}, pmid = {35645020}, issn = {1531-7056}, mesh = {Biomarkers ; *Celiac Disease/diagnosis ; Diet, Gluten-Free/methods ; Duodenum/pathology ; Glutens ; Humans ; }, abstract = {PURPOSE OF REVIEW: Different markers are available to diagnose and monitor celiac disease (CeD); however, the concordance among them and their efficacy are still controversial. We aim at defining the efficacy of CeD biomarkers, their advantages and limits.<br><br>RECENT FINDINGS: CeD diagnostic criteria are widely accepted, being a positive serology and duodenal atrophy (according to the Marsh-Oberhuber score) the main hallmarks. Flow cytometry and other molecular biomarkers support the diagnosis of refractory CeD. On the other side, CeD monitoring is less defined, as the biomarkers are not always reliable. To date, the reference standard to detect mucosal healing is represented by duodenal histology, but its timing and significance are debated. Novel scores may better define the trend of mucosal damage and MicroRNAs are among the innovative noninvasive biomarkers. The assessment of a correct gluten-free diet (GFD) is another aspect of CeD monitoring, based upon questionnaires and recently developed tools such as dosage of urinary or faecal gluten immunogenic peptides.<br><br>SUMMARY: Clinicians lack of a widely acknowledged tools to monitor CeD and GFD. Here, we present the efficacy of the most used markers.}, }
@article {pmid35643532, year = {2022}, author = {He, Z and Ma, Y and Yang, S and Zhang, S and Liu, S and Xiao, J and Wang, Y and Wang, W and Yang, H and Li, S and Cao, Z}, title = {Gut microbiota-derived ursodeoxycholic acid from neonatal dairy calves improves intestinal homeostasis and colitis to attenuate extended-spectrum β-lactamase-producing enteroaggregative Escherichia coli infection.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {79}, pmid = {35643532}, issn = {2049-2618}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacteria/metabolism ; Caco-2 Cells ; Cattle ; *Colitis/drug therapy ; Diarrhea/drug therapy/microbiology ; Escherichia coli ; *Escherichia coli Infections/drug therapy/veterinary ; *Gastrointestinal Microbiome ; Homeostasis ; Humans ; Mice ; *Sepsis ; Ursodeoxycholic Acid/pharmacology/therapeutic use ; beta-Lactamases/metabolism ; }, abstract = {BACKGROUND: Antimicrobials are often used to prevent and treat diarrhea induced by enteroaggregative Escherichia coli (EAEC) in young ruminants. However, drug overuse or misuse accelerates the spread of multidrug-resistant extended-spectrum β-lactamase (ESBL)-producing E. coli. Thus, supplementary foods as alternatives to antibiotics are needed to prevent colibacillus diarrhea in neonatal dairy calves. Ursodeoxycholic acid (UDCA), a therapeutic bile acid, helps alleviate colitis. However, how UDCA helps alleviate ESBL-EAEC-induced clinical symptoms and colitis remains unclear.<br><br>RESULTS: We investigated the microbial profiles and metabolites of healthy and diarrheic neonatal calves to determine microbial and metabolite biomarkers in early-life development. Both the gut microbiota communities and their associated metabolites differed between healthy and diarrheic calves. Commensal Butyricicoccus, Faecalibacterium, Ruminococcus, Collinsella, and Coriobacterium were key microbial markers that distinguished healthy and diarrheic gut microbiomes. Random forest machine-learning algorithm and Spearman correlation results indicated that enriched UDCA, short-chain fatty acids (SCFAs), and other prebiotics were strongly positively correlated with these five bacterial genera. We explored the effect of ursodiol on bacterial growth, cell adherence, and lipopolysaccharide-treated Caco-2 cells. Adding ursodiol induced direct antibacterial effects, suppressed proinflammatory effects, and reduced cell integrity damage. Oral ursodiol delivery to neonatal mice exhibited significant antibacterial effects and helped maintain colonic barrier integrity in mouse models of peritonitis sepsis and oral infection. UDCA supplementation attenuated colitis and recovered colonic SCFA production. To validate this, we performed fecal microbiota transplantations to inoculate ESBL-EAEC-infected neonatal mice. Microbiotas from UDCA-treated neonatal mice ameliorated colitis and hindgut commensal bacterial damage compared with that of the microbiotas from the control and placebo mice, as evidenced by colonization of abundant bacteria, including Oscillospiraceae, Ruminococcaceae, Lachnospiraceae, and Clostridia_UCG-014, and upregulated SCFA production.<br><br>CONCLUSIONS: This study provided the first evidence that UDCA could confer diarrhea resistance in ESBL-EAEC-infected newborn dairy calves. UDCA blocked bacterial growth and invasion both in vitro and in vivo, alleviated commensal bacterial dysbiosis during ESBL-EAEC infection in neonatal mouse models of sepsis and colitis via the TGR5-NF-&#x3ba;B axis, and upregulated SCFA production in the hindgut digesta. Our findings provide insight into the UDCA-mediated remission of ESBL-EAEC infections and the potential role of UDCA as an antibiotic alternative. Video abstract.}, }
@article {pmid35642928, year = {2022}, author = {Liu, Q and Zuo, T and Lu, W and Yeoh, YK and Su, Q and Xu, Z and Tang, W and Yang, K and Zhang, F and Lau, LHS and Lui, RNS and Chin, ML and Wong, R and Cheung, CP and Zhu, W and Chan, PKS and Chan, FKL and Lui, GC and Ng, SC}, title = {Longitudinal Evaluation of Gut Bacteriomes and Viromes after Fecal Microbiota Transplantation for Eradication of Carbapenem-Resistant Enterobacteriaceae.}, journal = {mSystems}, volume = {7}, number = {3}, pages = {e0151021}, pmid = {35642928}, issn = {2379-5077}, mesh = {Animals ; Mice ; Fecal Microbiota Transplantation ; *Carbapenem-Resistant Enterobacteriaceae ; Virome ; Escherichia coli ; Pilot Projects ; *Bacteriophages ; }, abstract = {Understanding the role of fecal microbiota transplantation (FMT) in the decolonization of multidrug-resistant organisms (MDRO) is critical. Specifically, little is known about virome changes in MDRO-infected subjects treated with FMT. Using shotgun metagenomic sequencing, we characterized longitudinal dynamics of the gut virome and bacteriome in three recipients who successfully decolonized carbapenem-resistant Enterobacteriaceae (CRE), including Klebsiella spp. and Escherichia coli, after FMT. We observed large shifts of the fecal bacterial microbiota resembling a donor-like community after transfer of a fecal microbiota dominated by the genus Ruminococcus. We found a substantial expansion of Klebsiella phages after FMT with a concordant decrease of Klebsiella spp. and striking increase of Escherichia phages in CRE E. coli carriers after FMT. We also observed the CRE elimination and similar evolution of Klebsiella phage in mice, which may play a role in the collapse of the Klebsiella population after FMT. In summary, our pilot study documented bacteriome and virome alterations after FMT which mediate many of the effects of FMT on the gut microbiome community. IMPORTANCE Fecal microbiota transplantation (FMT) is an effective treatment for multidrug-resistant organisms; however, introducing a complex mixture of microbes also has unknown consequences for landscape features of gut microbiome. We sought to understand bacteriome and virome alterations in patients undergoing FMT to treat infection with carbapenem-resistant Enterobacteriaceae. This finding indicates that transkingdom interactions between the virome and bacteriome communities may have evolved in part to support efficient FMT for treating CRE.}, }
@article {pmid35642838, year = {2022}, author = {Fang, H and Wang, Y and Deng, J and Zhang, H and Wu, Q and He, L and Xu, J and Shao, X and Ouyang, X and He, Z and Zhou, Q and Wang, H and Deng, Y and Chen, C}, title = {Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice.}, journal = {mSystems}, volume = {7}, number = {3}, pages = {e0139921}, pmid = {35642838}, issn = {2379-5077}, mesh = {Mice ; Animals ; *Sepsis-Associated Encephalopathy/metabolism ; Dysbiosis/etiology ; Neuroinflammatory Diseases ; NLR Family, Pyrin Domain-Containing 3 Protein ; RNA, Ribosomal, 16S/genetics ; Inflammasomes ; *Sepsis/complications ; }, abstract = {Sepsis-associated encephalopathy (SAE) is common in septic patients and is associated with adverse outcomes. The gut microbiota has been recognized as a key mediator of neurological disease development. However, the exact role of the gut microbiota in regulating SAE remains elusive. Here, we investigated the role of the gut microbiota in SAE and its underlying mechanisms. Cecal ligation and puncture (CLP) was conducted to induce sepsis in mice. Neurological scores were recorded to distinguish SAE-resistant (SER) (score of >6 at 36 h postoperatively) from SAE-susceptible (SES) (score of ≤6 at 36 h postoperatively) mice. 16S rRNA gene sequencing and metabolomics analyses were used to characterize the gut microbiota in the two groups. Fecal microbiota transplantation was performed to validate the role of the gut microbiota in SAE progression. The gut microbiota was more severely disrupted in SES mice than in SER mice after sepsis modeling. Interestingly, mice receiving postoperative feces from SES mice exhibited more severe cortical inflammation than mice receiving feces from SER mice. Indole-3-propionic acid (IPA), a neuroprotective molecule, was more enriched in feces from SER mice than in feces from SES mice. IPA alleviated CLP-induced anxiety and spatial memory impairment in septic mice. Moreover, IPA markedly inhibited NLRP3 inflammasome activation and interleukin-1β (IL-1β) secretion in lipopolysaccharide-stimulated microglia. These responses were attenuated after antagonizing the aryl hydrocarbon receptor. Our study indicates that the variability in sepsis-induced gut dysbiosis mediates the differential susceptibility to SAE in CLP-induced experimental sepsis mice, and microbially derived IPA is possibly involved in SAE development as a neuroprotective compound. IMPORTANCE The bidirectional interactions between the gut microbiota and sepsis-associated encephalopathy (SAE) are not well characterized. We found that the gut microbiota was more severely disturbed in SAE-susceptible (SES) mice than in SAE-resistant (SER) mice after sepsis modeling. Mice gavaged with postoperative feces from SES mice exhibited more severe neuroinflammation than mice gavaged with feces from SER mice. The gut microbiota from SER mice enriched a neuroprotective metabolite, IPA, which appeared to protect mice from SAE. The potential underlying mechanism of the protective effect of IPA may be mediated via the inhibition of NLRP3 inflammasome activation and IL-1β secretion in microglia. These anti-inflammatory effects of IPA may be regulated by aryl hydrocarbon receptors. These results enhance our understanding of the role of the intestinal microbiota in sepsis. In particular, gut microbiota-derived IPA may serve as a potential therapeutic agent to prevent neuroinflammation in SAE.}, }
@article {pmid35637497, year = {2022}, author = {Zhou, Q and Deng, J and Pan, X and Meng, D and Zhu, Y and Bai, Y and Shi, C and Duan, Y and Wang, T and Li, X and Sluijter, JP and Xiao, J}, title = {Gut microbiome mediates the protective effects of exercise after myocardial infarction.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {82}, pmid = {35637497}, issn = {2049-2618}, mesh = {Animals ; Feces ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; *Microbiota ; *Myocardial Infarction ; }, abstract = {BACKGROUND: Gut microbiota plays important roles in health maintenance and diseases. Physical exercise has been demonstrated to be able to modulate gut microbiota. However, the potential role of gut microbiome in exercise protection to myocardial infarction (MI) remains unclear.<br><br>RESULTS: Here, we discovered exercise training ameliorated cardiac dysfunction and changed gut microbial richness and community structure post-MI. Moreover, gut microbiota pre-depletion abolished the protective effects of exercise training in MI mice. Furthermore, mice receiving microbiota transplants from exercised MI mice had better cardiac function compared to mice receiving microbiota transplants from non-exercised MI mice. Mechanistically, we analyzed metabolomics in fecal samples from exercised mice post-MI and identified 3-Hydroxyphenylacetic acid (3-HPA) and 4-Hydroxybenzoic acid (4-HBA), which could be applied individually to protect cardiac dysfunction post-MI and apoptosis through NRF2.<br><br>CONCLUSIONS: Together, our study provides new insights into the role of gut microbiome in exercise protection to MI, offers opportunities to modulate cardiovascular diseases by exercise, microbiome and gut microbiota-derived 3-HPA and 4-HBA. Video Abstract.}, }
@article {pmid35635005, year = {2022}, author = {Li, WJ and Zhang, L and Wu, HX and Li, M and Wang, T and Zhang, WB and Du, ZY and Zhang, ML}, title = {Intestinal Microbiota Mediates Gossypol-Induced Intestinal Inflammation, Oxidative Stress, and Apoptosis in Fish.}, journal = {Journal of agricultural and food chemistry}, volume = {70}, number = {22}, pages = {6688-6697}, doi = {10.1021/acs.jafc.2c01263}, pmid = {35635005}, issn = {1520-5118}, mesh = {Animal Feed/analysis ; Animals ; Apoptosis ; *Cichlids/genetics ; Diet/veterinary ; Dietary Supplements ; *Gastrointestinal Microbiome ; *Gossypol/toxicity ; Inflammation/chemically induced ; Oxidative Stress ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Gossypol, the main antinutritional factor in cottonseed protein concentrate (CPC), could affect the growth conditions of fish, but the underlying mechanism remains unclear. In this study, an 8-week feeding trial was carried out to investigate the effects of gossypol on Nile tilapia (Oreochromis niloticus). Three experimental diets were designed, including control diet (CON), control diet supplemented with 150 mg/kg gossypol (ML), and 300 mg/kg gossypol (MH). 16S rRNA gene sequencing showed that gossypol significantly reduced the richness and diversity of the gut microbiota. Untargeted metabolite analysis revealed that most metabolites were down-regulated by gossypol, and riboflavin was the key metabolite with significant difference between CON-treated and gossypol-treated groups. Gossypol caused intestinal inflammation, oxidative stress, and apoptosis. Through fecal bacteria transplantation experiments, we demonstrated that intestinal microbiota mediated gossypol-induced negative effects, suggesting that intestinal microbiota and its metabolite may account for the harmful effects of gossypol.}, }
@article {pmid35634716, year = {2022}, author = {González-Dávila, P and Schwalbe, M and Danewalia, A and Wardenaar, R and Dalile, B and Verbeke, K and Mahata, SK and El Aidy, S}, title = {Gut microbiota transplantation drives the adoptive transfer of colonic genotype-phenotype characteristics between mice lacking catestatin and their wild type counterparts.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2081476}, pmid = {35634716}, issn = {1949-0984}, support = {I01 BX003934/BX/BLRD VA/United States ; }, mesh = {Adoptive Transfer ; Animals ; Chromogranin A ; Colon ; *Gastrointestinal Microbiome/physiology ; Genotype ; Mice ; Peptide Fragments ; Phenotype ; Phylogeny ; }, abstract = {The gut microbiota is in continuous interaction with the intestinal mucosa via metabolic, neuro-immunological, and neuroendocrine pathways. Disruption in levels of antimicrobial peptides produced by the enteroendocrine cells, such as catestatin, has been associated with changes in the gut microbiota and imbalance in intestinal homeostasis. However, whether the changes in the gut microbiota have a causational role in intestinal dyshomeostasis has remained elusive. To this end, we performed reciprocal fecal microbial transplantation in wild-type mice and mice with a knockout in the catestatin coding region of the chromogranin-A gene (CST-KO mice). Combined microbiota phylogenetic profiling, RNA sequencing, and transmission electron microscopy were employed. Fecal microbiota transplantation from mice deficient in catestatin (CST-KO) to microbiota-depleted wild-type mice induced transcriptional and physiological features characteristic of a distorted colon in the recipient animals, including impairment in tight junctions, as well as an increased collagen area fraction indicating colonic fibrosis. In contrast, fecal microbiota transplantation from wild-type mice to microbiota-depleted CST-KO mice reduced collagen fibrotic area, restored disrupted tight junction morphology, and altered fatty acid metabolism in recipient CST-KO mice. This study provides a comprehensive overview of the murine metabolic- and immune-related cellular pathways and processes that are co-mediated by the fecal microbiota transplantation and supports a prominent role for the gut microbiota in the colonic distortion associated with the lack of catestatin in mice. Overall, the data show that the gut microbiota may play a causal role in the development of features of intestinal inflammation and metabolic disorders, known to be associated with altered levels of catestatin and may, thus, provide a tractable target in the treatment and prevention of these disorders.}, }
@article {pmid35634319, year = {2022}, author = {Xia, Y and Shi, H and Qian, C and Han, H and Lu, K and Tao, R and Gu, R and Zhao, Y and Wei, Z and Lu, Y}, title = {Modulation of Gut Microbiota by Magnesium Isoglycyrrhizinate Mediates Enhancement of Intestinal Barrier Function and Amelioration of Methotrexate-Induced Liver Injury.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {874878}, pmid = {35634319}, issn = {1664-3224}, mesh = {*Chemical and Drug Induced Liver Injury, Chronic ; *Gastrointestinal Microbiome ; Humans ; *Liver Diseases/microbiology ; Methotrexate/adverse effects ; Saponins ; Triterpenes ; }, abstract = {BACKGROUND: The gut-liver axis plays a crucial role in various liver diseases. Therefore, targeting this crosstalk may provide a new treatment strategy for liver diseases. However, the exact mechanism underlying this crosstalk and its impact on drug-induced liver injury (DILI) requires clarification.<br><br>AIM: This study aimed to investigate the potential mechanism and therapeutic effect of MgIG on MTX-induced liver injury, which is associated with the gut-liver axis and gut microbiota.<br><br>METHODS: An MTX-induced liver injury model was generated after 20-mg/kg/3d MTX application for 30 days. Meanwhile, the treatment group was treated with 40-mg/kg MgIG daily. Histological examination, aminotransferase, and aspartate aminotransferase enzyme levels were estimated to evaluate liver function. Immune cells infiltration and inflammatory cytokines were detected to indicate inflammation levels. Colon histological score, intestinal barrier leakage, and expression of tight junctions were employed to assess the intestinal injury. Bacterial translocation was observed using fluorescent in situ hybridisation, colony-forming unit counting, and lipopolysaccharide detection. Alterations in gut microbial composition were analysed using 16s rDNA sequencing and relative quantitative polymerase chain reaction. Short-chain-fatty-acids and lactic acid concentrations were then utilized to validate changes in metabolites of specific bacteria. Lactobacillus sp. supplement and fecal microbiota transplantation were used to evaluate gut microbiota contribution.<br><br>RESULTS: MTX-induced intestinal and liver injuries were significantly alleviated using MgIG treatment. Bacterial translocation resulting from the intestinal barrier disruption was considered a crucial cause of MTX-induced liver injury and the therapeutic target of MgIG. Moreover, MgIG was speculated to have changed the gut microbial composition by up-regulating probiotic Lactobacillus and down-regulating Muribaculaceae, thereby remodelling the intestinal barrier and inhibiting bacterial translocation.<br><br>CONCLUSION: The MTX-induced intestinal barrier was protected owing to MgIG administration, which reshaped the gut microbial composition and inhibited bacterial translocation into the liver, thus attenuating MTX-related DILI.}, }
@article {pmid35631220, year = {2022}, author = {Yoo, JW and Shin, YJ and Ma, X and Son, YH and Jang, HM and Lee, CK and Kim, DH}, title = {The Alleviation of Gut Microbiota-Induced Depression and Colitis in Mice by Anti-Inflammatory Probiotics NK151, NK173, and NK175.}, journal = {Nutrients}, volume = {14}, number = {10}, pages = {}, pmid = {35631220}, issn = {2072-6643}, support = {2017R1A5A2014768//National Research Foundation of Korea/ ; }, mesh = {Animals ; Anti-Inflammatory Agents ; *Colitis/chemically induced/microbiology/therapy ; Creatinine ; Depression/psychology/therapy ; *Gastrointestinal Microbiome ; Humans ; Immunoglobulin M ; Inflammation/chemically induced/therapy ; *Inflammatory Bowel Diseases ; Interleukin-6 ; Lipopolysaccharides ; Mice ; NF-kappa B/metabolism ; *Probiotics ; }, abstract = {Gut microbiota dysbiosis is strongly associated with psychiatric disorders and inflammatory bowel disease (IBD). Herein, we examined whether the fecal microbiota of IBD patients with depression (IBDD) and their gut microbiota culture (iGm) could cause depression and colitis in mice and anti-inflammatory probiotics could mitigate depression in iGm-transplanted or immobilization stress (IS)-exposed mice. Fecal microbiota transplantation (FMT) from IBDD patients, which exhibited Enterobacteriaceae-rich gut microbiota, and its gut microbiota culture (iGm) increased depression-like behaviors in mice. Their treatments heightened the blood lipopolysaccharide (LPS) level and colonic IL-1β and IL-6 expression. However, FMT from healthy volunteers or sulfasalazine treatment alleviated cGm-induced depressive-like behaviors and hippocampal and colonic inflammation in mice. Moreover, oral administration of Lactobacillus plantarum NK151, Bifidobacterium longum NK173, and Bifidobacterium bifidum NK175, which inhibited LPS-induced IL-6 expression in macrophages, alleviated cGm-induced depression-like behaviors, hippocampal NF-κB[+]Iba1[+] cell numbers and IL-1β and IL-6 expression, blood LPS, IL-6, and creatinine levels, and colonic NF-κB[+]CD11c[+] number and IL-1β and IL-6 expression in mice. Treatment with NK151, NK173, or NK175 mitigated immobilization stress (IS)-induced depressive-like behaviors, neuroinflammation, and gut inflammation in mice. NK151, NK173, or NK175 also decreased IS-induced blood LPS, IL-6, and creatinine levels. The transplantation of Enterobacteriaceae-rich gut microbiota can cause depression and colitis, as IS exposure, and anti-inflammatory NK151, NK173, and NK175, may alleviate stress-induced fatigue, depression, and colitis by regulating the expression of proinflammatory and anti-inflammatory cytokines through the suppression of gut bacterial LPS.}, }
@article {pmid35631150, year = {2022}, author = {Wang, P and Ma, Y and Wang, D and Zhao, W and Hu, X and Chen, F and Zhao, X}, title = {Protective Effects of Dietary Resveratrol against Chronic Low-Grade Inflammation Mediated through the Gut Microbiota in High-Fat Diet Mice.}, journal = {Nutrients}, volume = {14}, number = {10}, pages = {}, pmid = {35631150}, issn = {2072-6643}, support = {32101959//National Natural Science Foundation of China/ ; 202244/WT_/Wellcome Trust/United Kingdom ; KJCX201915//the Collaborative Innovation Center of Beijing Academy of Agricultural and Forestry Sciences/ ; KJCX20200208//Scientific and Technological Innovation Ability Foundation of Beijing Academy of Agricultural and Forestry Sciences/ ; CARS-23//China Agriculture Research System of MOF and MRAR/ ; }, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Inflammation ; Mice ; Mice, Inbred C57BL ; Obesity/microbiology/therapy ; Resveratrol/pharmacology ; }, abstract = {Resveratrol (RSV), a natural polyphenol, has been shown to exert activity against obesity and related chronic inflammation. However, due to the poor bioavailability of RSV, the mechanisms of RSV against inflammation in obesity models remain unclear. In this study, we aimed to investigate the relationship between the gut bacteria and the anti-inflammation effects of RSV in HFD-fed mice. We found that RSV supplementation reduced fat accumulation and improved systemic inflammation in HFD-fed mice. Meanwhile, RSV attenuated HFD-induced changes in the gut microbiota's structure, which were associated with inflammatory parameters. A fecal microbiota transplantation (FMT) experiment proved that the anti-inflammation effects of RSV largely rely on the gut microbiota. Moreover, the microbiota-genera-changing trend in the FMT experiment was similar to that in the oral RSV-feeding experiment. Thus, these results demonstrate that modulation of the gut bacteria induced by RSV treatment has a therapeutic effect on chronic low-grade inflammation in HFD-fed mice.}, }
@article {pmid35630496, year = {2022}, author = {Gan, L and Bo, T and Liu, W and Wang, D}, title = {The Gut Microbiota May Affect Personality in Mongolian Gerbils.}, journal = {Microorganisms}, volume = {10}, number = {5}, pages = {}, pmid = {35630496}, issn = {2076-2607}, support = {31872232//National Natural Science Foundation of China/ ; 32090024//State Natural Sciences Foundation Monumental Projects/ ; XDPB16//Strategic Priority Research Program of Chinese Academy of Sciences/ ; 2021M693158//Postdoctoral Research Foundation of China/ ; }, abstract = {The "gut-microbiota-brain axis" reveals that gut microbiota plays a critical role in the orchestrating behavior of the host. However, the correlation between the host personalities and the gut microbiota is still rarely known. To investigate whether the gut microbiota of Mongolian gerbils (Meriones unguiculatus) differs between bold and shy personalities, we compared the gut microbiota of bold and shy gerbils, and then we transplanted the gut microbiota of bold and shy gerbils into middle group gerbils (individuals with less bold and shy personalities). We found a significant overall correlation between host boldness and gut microbiota. Even though there were no significant differences in alpha diversity and beta diversity of gut microbiota between bold and shy gerbils, the Firmicutes/Bacteroidetes phyla and Odoribacter and Blautia genus were higher in bold gerbils, and Escherichia_shigella genus was lower. Furthermore, the fecal microbiota transplantation showed that changes in gut microbiota could not evidently cause the increase or decrease in the gerbil's boldness score, but it increased the part of boldness behaviors by gavaging the "bold fecal microbiota". Overall, these data demonstrated that gut microbiota were significantly correlated with the personalities of the hosts, and alteration of microbiota could alter host boldness to a certain extent.}, }
@article {pmid35630347, year = {2022}, author = {Shang, L and Tu, J and Dai, Z and Zeng, X and Qiao, S}, title = {Microbiota Transplantation in an Antibiotic-Induced Bacterial Depletion Mouse Model: Reproducible Establishment, Analysis, and Application.}, journal = {Microorganisms}, volume = {10}, number = {5}, pages = {}, pmid = {35630347}, issn = {2076-2607}, support = {32030105//National Key Research and Development Program of China/ ; cstc2019ngzx0019//Chongqing Rongchang Agricultural and Animal Husbandry High-tech Industry Research and Development Project/ ; }, abstract = {The fecal bacteria transplantation (FMT) technique is indispensable when exploring the pathogenesis and potential treatments for microbiota-related diseases. For FMT clinical treatments, there are already systematic guidelines for donor selection, fecal bacterial separation, FMT frequency, and infusion methods. However, only a few studies have demonstrated the use of standardized FMT procedures for animal models used in theoretical research, creating difficulties for many new researchers in this field. In the present paper, we provide a brief overview of FMT and discuss its contribution to the current understanding of disease mechanisms that relate to microbiota. This protocol can be used to generate a commonly used FMT mouse model and provides a literature reference of customizable steps.}, }
@article {pmid35629390, year = {2022}, author = {Takáčová, M and Bomba, A and Tóthová, C and Micháľová, A and Turňa, H}, title = {Any Future for Faecal Microbiota Transplantation as a Novel Strategy for Gut Microbiota Modulation in Human and Veterinary Medicine?.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {35629390}, issn = {2075-1729}, support = {1/0314/20//VEGA from the Ministry of Education, Science, Research and Sport of the Slovak Republic./ ; 1/0177/22//VEGA from the Ministry of Education, Science, Research and Sport of the Slovak Republic./ ; }, abstract = {Alterations in the composition of the intestinal microbiome, also known as dysbiosis, are the result of many factors such as diet, antibiotics, stress, diseases, etc. There are currently several ways to modulate intestinal microbiome such as dietary modulation, the use of antimicrobials, prebiotics, probiotics, postbiotics, and synbiotics. Faecal microbiota transplantation (FMT) represents one new method of gut microbiota modulation in humans with the aim of reconstructing the intestinal microbiome of the recipient. In human medicine, this form of bacteriotherapy is successfully used in cases of recurrent Clostridium difficile infection (CDI). FMT has been known in large animal medicine for several years. In small animal medicine, the use of FMT is not part of normal practice.}, }
@article {pmid35625513, year = {2022}, author = {Ugrayová, S and Švec, P and Hric, I and Šardzíková, S and Kubáňová, L and Penesová, A and Adamčáková, J and Pačesová, P and Horáková, J and Kolenová, A and Šoltys, K and Kolisek, M and Bielik, V}, title = {Gut Microbiome Suffers from Hematopoietic Stem Cell Transplantation in Childhood and Its Characteristics Are Positively Associated with Intra-Hospital Physical Exercise.}, journal = {Biology}, volume = {11}, number = {5}, pages = {}, pmid = {35625513}, issn = {2079-7737}, support = {APVV-17-0099//Slovak Research and Development Agency/ ; APVV-19-0222//Slovak Research and Development Agency/ ; No. MAGDG2000059//Grant program for the development of sport and education in the capital of the Slovak Republic in Bratislava/ ; UK/38/20//Comenius University/ ; UK/112/2021//Comenius University/ ; VEGA 1/0260/21//Vedeck&#xe1; grantov&#xe1; agent&#xfa;ra M&#x160;VVa&#x160; SR a SAV (VEGA)/ ; }, abstract = {Gut microbiome impairment is a serious side effect of cancer treatment. The aim of this study was to identify the effects of hematopoietic stem cell transplantation (HSCT) treatment on gut microbiota composition in children with acute lymphoblastic leukemia (ALL). Fecal microbiotas were categorized using specific primers targeting the V1-V3 region of 16S rDNA in eligible pediatric ALL patients after HSCT (n = 16) and in healthy controls (Ctrl, n = 13). An intra-hospital exercise program was also organized for child patients during HSCT treatment. Significant differences in gut microbiota composition were observed between ALL HSCT and Ctrl with further negative effects. Plasma C-reactive protein correlated positively with the pathogenic bacteria Enterococcus spp. and negatively with beneficial bacteria Butyriccocus spp. or Akkermansia spp., respectively (rs = 0.511, p = 0.05; rs = -0.541, p = 0.04; rs = -0.738, p = 0.02). Bacterial alpha diversity correlated with the exercise training characteristics. Therefore, specific changes in the microbiota of children were associated with systemic inflammation or the ability to exercise physically during HSCT treatment.}, }
@article {pmid35625485, year = {2022}, author = {Dey, P and Ray Chaudhuri, S}, title = {Cancer-Associated Microbiota: From Mechanisms of Disease Causation to Microbiota-Centric Anti-Cancer Approaches.}, journal = {Biology}, volume = {11}, number = {5}, pages = {}, pmid = {35625485}, issn = {2079-7737}, support = {SRG/2021/000082//Science and Engineering Research Board/ ; }, abstract = {Helicobacter pylori infection is the only well-established bacterial cause of cancer. However, due to the integral role of tissue-resident commensals in maintaining tissue-specific immunometabolic homeostasis, accumulated evidence suggests that an imbalance of tissue-resident microbiota that are otherwise considered as commensals, can also promote various types of cancers. Therefore, the present review discusses compelling evidence linking tissue-resident microbiota (especially gut bacteria) with cancer initiation and progression. Experimental evidence supporting the cancer-causing role of gut commensal through the modulation of host-specific processes (e.g., bile acid metabolism, hormonal effects) or by direct DNA damage and toxicity has been discussed. The opportunistic role of commensal through pathoadaptive mutation and overcoming colonization resistance is discussed, and how chronic inflammation triggered by microbiota could be an intermediate in cancer-causing infections has been discussed. Finally, we discuss microbiota-centric strategies, including fecal microbiota transplantation, proven to be beneficial in preventing and treating cancers. Collectively, this review provides a comprehensive understanding of the role of tissue-resident microbiota, their cancer-promoting potentials, and how beneficial bacteria can be used against cancers.}, }
@article {pmid35624084, year = {2022}, author = {Jee, JJ and Lim, J and Park, S and Koh, H and Lee, HW}, title = {Gut microbial community differentially characterizes patients with nonalcoholic fatty liver disease.}, journal = {Journal of gastroenterology and hepatology}, volume = {37}, number = {9}, pages = {1822-1832}, doi = {10.1111/jgh.15903}, pmid = {35624084}, issn = {1440-1746}, mesh = {Enterobacteriaceae ; *Gastrointestinal Microbiome ; Humans ; Interleukin-6/metabolism ; Liver/pathology ; *Non-alcoholic Fatty Liver Disease/pathology ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND AND AIM: Discordant reports of the signature gut microbes involved in nonalcoholic fatty liver disease (NAFLD) have hampered understanding of the pathogenesis of the disease, and thus its diagnosis. Thus, we investigated diagnostic factors and the potential mechanisms for heterogenous NAFLD based on the gut environment, including microbes and functional pathways.<br><br>METHODS: Stools from 16 biopsy-proven NAFLD patients were analyzed for bacterial taxonomy and functional pathways based on 16s rRNA gene sequencing. Data from the physical examination, serum biochemistry, and the gut environment were subjected to a decision tree classifier to identify diagnostic markers.<br><br>RESULTS: We identified two NAFLD subpopulations: those with and without a gut microbiota similar to health controls (HCs), defined as PHC-like and P patients, respectively. Stools of PHC-like patients were significantly populated with Enterobacteriaceae and were inferred to be rich in metabolites degraded from dicarboxylic acid sugars. Significant colonization of Prevotella was observed in the stools of P patients, in parallel with enrichment of metabolites from heme b biosynthesis and sulfate reduction. As a potential mechanism, we suggest that protoporphyrin IX and/or protoheme from Prevotella participates in hepatic injury, and that endogenous hydrogen sulfide increases serum IL-6 level in P patients. However, endotoxin-producing Enterobacteriaceae are thought to produce glycerate, triggering a peroxisome proliferator- activated receptor-alpha-mediated decrease in IL-6 level and fat accumulation in PHC-like patients.<br><br>CONCLUSIONS: Heterogenous NAFLD subpopulations were identified, defined according to gut microbial composition and their potential underlying pathogenic mechanisms; our results raise the possibility of personalized treatment for NALFD patients.}, }
@article {pmid35623598, year = {2022}, author = {Pane, K and Boccella, S and Guida, F and Franzese, M and Maione, S and Salvatore, M}, title = {Role of gut microbiota in neuropathy and neuropathic pain states: A systematic preclinical review.}, journal = {Neurobiology of disease}, volume = {170}, number = {}, pages = {105773}, doi = {10.1016/j.nbd.2022.105773}, pmid = {35623598}, issn = {1095-953X}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Neuralgia ; }, abstract = {Gut microbiota has implications in Central Nervous System (CNS) disorders. Our study systematically identified preclinical studies aimed to investigate the possible gut microbiota contribution in neuropathy and neuropathic pain. The systematic review is reported in accordance with PRISMA checklist and guidelines outlined updated to 2020. We included research articles reporting neuropathy-related behavioral evaluations and/or neurological scores coupled to gut microbiota analysis performed by high-throughput technologies in the last ten years. Two investigators performed a search through 3 electronic bibliographic databases for full-text articles (PubMed, Scopus, and EMBASE) and three registries (Prospero, SyRF, and bioRxiv), cross-references, and linear searches. We assessed the methodological quality via the CAMARADES checklist and appraised the heterogeneous body of evidence by narrative synthesis. In total, there were 19 eligible studies. The most of these reports showed significant changes in gut microbiota setting in neuropathy conditions. The major gut microbiome remodeling was through fecal microbiome transplantation. Mechanistic proof of the gut-CNS communication was achieved by measuring inflammatory mediators, metabolic products, or neurotransmitters. As a limitation, we found considerable heterogeneity across eligible studies. We conclude that the current understanding of preclinical findings suggested an association between neuropathy and/or neuropathic pain and gut microbiota modifications. Our analysis provides the basis for further studies targeting microbiota for managing symptoms of neuropathy or other neuroinflammation-based CNS disorders. The systematic review protocol was registered on the international database Prospero under the registration number (257628).}, }
@article {pmid35620724, year = {2022}, author = {Hu, Y and Ye, Z and Wu, M and She, Y and Li, L and Xu, Y and Qin, K and Hu, Z and Yang, M and Lu, F and Ye, Q}, title = {Corrigendum: The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {886105}, doi = {10.3389/fmed.2022.886105}, pmid = {35620724}, issn = {2296-858X}, abstract = {[This corrects the article DOI: 10.3389/fmed.2021.766126.].}, }
@article {pmid35619714, year = {2022}, author = {Zhang, B and Chen, T and Cao, M and Yuan, C and Reiter, RJ and Zhao, Z and Zhao, Y and Chen, L and Fan, W and Wang, X and Zhou, X and Li, C}, title = {Gut Microbiota Dysbiosis Induced by Decreasing Endogenous Melatonin Mediates the Pathogenesis of Alzheimer's Disease and Obesity.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {900132}, pmid = {35619714}, issn = {1664-3224}, mesh = {*Alzheimer Disease/etiology ; Animals ; Dysbiosis ; *Gastrointestinal Microbiome ; Inflammation ; *Melatonin/pharmacology ; Mice ; Obesity/metabolism ; }, abstract = {Lifestyle choices, external environment, aging, and other factors influence the synthesis of melatonin. Although the physiological functions of melatonin have been widely studied in relation to specific organs, the systemic effects of endogenous melatonin reduction has not been reported. This study evaluates the systemic changes and possible pathogenic risks in an endogenous melatonin reduction (EMR) mouse model deficient in the rate limiting enzyme in melatonin production, arylalkylamine N-acetyltransferase (Aanat) gene. Using this model, we identified a new relationship between melatonin, Alzheimer's disease (AD), and gut microbiota. Systematic changes were evaluated using multi-omics analysis. Fecal microbiota transplantation (FMT) was performed to examine the role of gut microbiota in the pathogenic risks of EMR. EMR mice exhibited a pan-metabolic disorder, with significant transcriptome changes in 11 organs, serum metabolome alterations as well as microbiota dysbiosis. Microbiota dysbiosis was accompanied by increased gut permeability along with gut and systemic inflammation. Correlation analysis revealed that systemic inflammation may be related to the increase of Ruminiclostridium_5 relative abundance. 8-month-old EMR mice had AD-like phenotypes, including Iba-1 activation, A β protein deposition and decreased spatial memory ability. Moreover, EMR mice showed decreased anti stress ability, under high-fat diet, EMR mice had greater body weight and more obvious hepatic steatosis compared with WT group. FMT improved gut permeability, systemic inflammation, and AD-related phenotypes, while reducing obesity in EMR mice. Our findings suggest EMR causes systemic changes mediated by gut microbiota dysbiosis, which may be a pathogenic factor for AD and obesity, we further proved the gut microbiota is a potential target for the prevention and treatment of AD and obesity.}, }
@article {pmid35619175, year = {2022}, author = {Chen, C and Chen, L and Sun, D and Li, C and Xi, S and Ding, S and Luo, R and Geng, Y and Bai, Y}, title = {Adverse events of intestinal microbiota transplantation in randomized controlled trials: a systematic review and meta-analysis.}, journal = {Gut pathogens}, volume = {14}, number = {1}, pages = {20}, pmid = {35619175}, issn = {1757-4749}, abstract = {BACKGROUND: Intestinal microbiota transplantation (IMT) has been recognized as an effective treatment for recurrent Clostridium difficile infection (rCDI) and a novel treatment option for other diseases. However, the safety of IMT in patients has not been established.<br><br>AIMS: This systematic review and meta-analysis was conducted to assess the safety of IMT.<br><br>METHODS: We systematically reviewed all randomized controlled trials (RCTs) of IMT studies published up to 28 February 2021 using databases including PubMed, EMBASE and the Cochrane Library. Studies were excluded if they did not report adverse events (AEs). Two authors independently extracted the data. The relative risk (RR) of serious adverse events (SAEs) and common adverse events (CAEs) were estimated separately, as were predefined subgroups. Publication bias was evaluated by a funnel plot and Egger's regression test.<br><br>RESULTS: Among 978 reports, 99 full-text articles were screened, and 20 articles were included for meta-analysis, involving 1132 patients (603 in the IMT group and 529 in the control group). We found no significant difference in the incidence of SAEs between the IMT group and the control group (RR&#x2009;=&#x2009;1.36, 95% CI&#x2009;0.56-3.31, P&#x2009;=&#x2009;0.50). Of these 20 studies, 7 described the number of patients with CAEs, involving 360 patients (195 in the IMT group and 166 in the control group). An analysis of the eight studies revealed that the incidence of CAEs was also not significantly increased in the IMT group compared with the control group (RR&#x2009;=&#x2009;1.06, 95% CI&#x2009;&#x2009;0.91-1.23, P&#x2009;=&#x2009;0.43). Subgroup analysis showed that the incidence of CAEs was significantly different between subgroups of delivery methods (P(CAE)&#x2009;=&#x2009;0.04), and the incidence of IMT-related SAEs and CAEs was not significantly different in the other predefined subgroups.<br><br>CONCLUSION: Currently, IMT is widely used in many diseases, but its associated AEs should not be ignored. To improve the safety of IMT, patients' conditions should be fully evaluated before IMT, appropriate transplantation methods should be selected, each operative step of faecal bacteria transplantation should be strictly controlled, AE management mechanisms should be improved, and a close follow-up system should be established.}, }
@article {pmid35616308, year = {2022}, author = {Yan, X and Zhai, Y and Zhou, W and Qiao, Y and Guan, L and Liu, H and Jiang, J and Peng, L}, title = {Intestinal Flora Mediates Antiobesity Effect of Rutin in High-Fat-Diet Mice.}, journal = {Molecular nutrition &amp; food research}, volume = {66}, number = {14}, pages = {e2100948}, doi = {10.1002/mnfr.202100948}, pmid = {35616308}, issn = {1613-4133}, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/drug therapy/metabolism ; RNA, Ribosomal, 16S/genetics ; Rutin/pharmacology ; }, abstract = {SCOPE: Intestinal flora plays a critical role in the development of . Rutin is a natural flavonoid with potential prebiotic effects on regulating the intestinal flora composition that is beneficial for host health. Therefore, this study hypothesizes that rutin supplementation has beneficial effects on high-fat-diet (HFD)-induced obesity and metabolic disorder through the modulation of intestinal flora in mice.<br><br>METHODS AND RESULTS: The obesity-alleviating property of rutin using 6-week-old C57BL/6J male mice fed on HFD with or without rutin supplementation for 16 weeks is investigated. Rutin supplementation effectively reduces body-weight gain, insulin resistance, and acted favorably on the intestinal barrier, thereby reducing endotoxemia and systemic inflammation. Sequencing of 16S rRNA genes from fecal samples indicate that rutin exerted modulatory effects on HFD-induced intestinal flora disorders (e.g., rutin decreased Firmicutes abundance and increased Bacteroidetes and Verrucomicrobia abundance). Antibiotic treatment and fecal microbiota transplantation further demonstrate that the salutary effects of rutin on obesity control are strongly dependent on the intestinal flora.<br><br>CONCLUSION: Rutin can be considered as a prebiotic agent for improving intestinal flora disorders and obesity-associated metabolic perturbations in obese individuals.}, }
@article {pmid35613492, year = {2022}, author = {Fu, Y and Hu, J and Erasmus, MA and Johnson, TA and Cheng, HW}, title = {Effects of early-life cecal microbiota transplantation from divergently selected inbred chicken lines on growth, gut serotonin, and immune parameters in recipient chickens.}, journal = {Poultry science}, volume = {101}, number = {7}, pages = {101925}, pmid = {35613492}, issn = {1525-3171}, mesh = {Animal Feed/analysis ; Animals ; Cecum ; *Chickens/physiology ; Diet/veterinary ; Dietary Supplements ; Male ; *Microbiota ; Oviposition ; Serotonin ; }, abstract = {Recent studies have revealed that fecal microbiota transplantation exerts beneficial effects on modulating stress-related inflammation and gastrointestinal health of the host. The aim of this study was to examine if cecal microbiota transplantation (CMT) presents similar efficiency in improving the health status of egg-laying strain chickens. Chicken lines 63 and 72 divergently selected for resistance or susceptibility to Marek's disease were used as CMT donors. Eighty-four d-old male recipient chicks (a commercial DeKalb XL layer strain) were randomly assigned into 3 treatments with 7 replicates per treatment and 4 birds per replicate (n = 7): saline (control, CTRL), cecal solution of line 63 (63-CMT), and cecal solution of line 72 (72-CMT) for a 16-wk trial. Cecal transplant gavage was conducted once daily from d 1 to d 10, then boosted once weekly from wk 3 to wk 5. The results indicated that 72-CMT birds had the highest body weight and ileal villus/crypt ratio among the treatments at wk 5 (P ≤ 0.05); and higher heterophil/lymphocyte ratios than that of 63-CMT birds at wk 16 (P < 0.05). 72-CMT birds also had higher levels of plasma natural IgG and Interleukin (IL)-6 at wk 16, while 63-CMT birds had higher concentrations of ileal mucosal secretory IgA at wk 5 and plasma IL-10 at wk 16 (P < 0.05), with a tendency for lower mRNA abundance of splenic IL-6 and tumor necrosis factor (TNF)-α at wk 16 (P = 0.08 and 0.07, respectively). In addition, 72-CMT birds tended to have the lowest serotonin concentrations (P = 0.07) with the highest serotonin turnover in the ileum at wk 5 (P < 0.05). There were no treatment effects on the levels of plasma corticosterone and testosterone at wk 16 (P > 0.05). In conclusion, early postnatal CMT from different donors led to different patterns of growth and health status through the regulation of ileal morphological structures, gut-derived serotonergic activities, peripheral cytokines, and antibody production in recipient chickens.}, }
@article {pmid35613310, year = {2022}, author = {Luo, T and Guo, Z and Liu, D and Guo, Z and Wu, Q and Li, Q and Lin, R and Chen, P and Ou, C and Chen, M}, title = {Deficiency of PSRC1 accelerates atherosclerosis by increasing TMAO production via manipulating gut microbiota and flavin monooxygenase 3.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2077602}, pmid = {35613310}, issn = {1949-0984}, mesh = {Animals ; *Atherosclerosis/genetics/microbiology ; Bacteria/genetics/metabolism ; *Gastrointestinal Microbiome/physiology ; *Methylamines/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mixed Function Oxygenases/metabolism ; *Oxygenases/metabolism ; *Phosphoproteins/deficiency ; Plaque, Atherosclerotic/metabolism/microbiology ; }, abstract = {Maladaptive inflammatory and immune responses are responsible for intestinal barrier integrity and function dysregulation. Proline/serine-rich coiled-coil protein 1 (PSRC1) critically contributes to the immune system, but direct data on the gut microbiota and the microbial metabolite trimethylamine N-oxide (TMAO) are lacking. Here, we investigated the impact of PSRC1 deletion on TMAO generation and atherosclerosis. We first found that PSRC1 deletion in apoE[-/-] mice accelerated atherosclerotic plaque formation, and then the gut microbiota and metabolites were detected using metagenomics and untargeted metabolomics. Our results showed that PSRC1 deficiency enriched trimethylamine (TMA)-producing bacteria and functional potential for TMA synthesis and accordingly enhanced plasma betaine and TMAO production. Furthermore, PSRC1 deficiency resulted in a proinflammatory colonic phenotype that was significantly associated with the dysregulated bacteria. Unexpectedly, hepatic RNA-seq indicated upregulated flavin monooxygenase 3 (FMO3) expression following PSRC1 knockout. Mechanistically, PSRC1 overexpression inhibited FMO3 expression in vitro, while an ERα inhibitor rescued the downregulation. Consistently, PSRC1-knockout mice exhibited higher plasma TMAO levels with a choline-supplemented diet, which was gut microbiota dependent, as evidenced by antibiotic treatment. To investigate the role of dysbiosis induced by PSRC1 deletion in atherogenesis, apoE[-/-] mice were transplanted with the fecal microbiota from either apoE[-/-] or PSRC1[-/-]apoE[-/-] donor mice. Mice that received PSRC1-knockout mouse feces showed an elevation in TMAO levels, as well as plaque lipid deposition and macrophage accumulation, which were accompanied by increased plasma lipid levels and impaired hepatic cholesterol transport. Overall, we identified PSRC1 as an atherosclerosis-protective factor, at least in part, attributable to its regulation of TMAO generation via a multistep pathway. Thus, PSRC1 holds great potential for manipulating the gut microbiome and alleviating atherosclerosis.}, }
@article {pmid35611465, year = {2022}, author = {Gulliver, EL and Young, RB and Chonwerawong, M and D'Adamo, GL and Thomason, T and Widdop, JT and Rutten, EL and Rossetto Marcelino, V and Bryant, RV and Costello, SP and O'Brien, CL and Hold, GL and Giles, EM and Forster, SC}, title = {Review article: the future of microbiome-based therapeutics.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {56}, number = {2}, pages = {192-208}, pmid = {35611465}, issn = {1365-2036}, mesh = {Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {BACKGROUND: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic.<br><br>AIM: This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development.<br><br>METHODS: Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical interventions. Key literature was identified through Pubmed searches with the following key words, 'microbiome', 'microbiome biomarkers', 'probiotics', 'prebiotics', 'synbiotics', 'faecal microbiota transplant', 'live biotherapeutics', 'microbiome mimetics' and 'postbiotics'.<br><br>RESULTS: Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, rationally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics.<br><br>CONCLUSIONS: Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation.}, }
@article {pmid35610004, year = {2022}, author = {Zeyue, YU and Liyu, H and Zongyuan, LI and Jianhui, S and Hongying, C and Hairu, H and Xiaoqin, LI and Zhongchao, S and Hongmei, LI}, title = {Correlation between slow transit constipation and spleen deficiency, and gut microbiota: a pilot study.}, journal = {Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan}, volume = {42}, number = {3}, pages = {353-363}, pmid = {35610004}, issn = {2589-451X}, mesh = {Animals ; Constipation/drug therapy ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Mice ; Mice, Inbred ICR ; Pilot Projects ; Spleen ; Xylose/therapeutic use ; }, abstract = {OBJECTIVE: To investigate the effect of slow transit constipation (STC) and spleen deficiency on gut microbiota, and the mechanism underlying the action that the positive drug Maren Runchang (MR) alleviates STC.<br><br>METHODS: STC was induced, using the cathartic method of Senna and the hunger-fullness disorder method, in ICR mice; one group of model mice was treated with MR (6.24 g/kg). The changes in the general condition, fecal parameters, D-xylose content in the serum, intestinal propulsion rate, and histopathology of the colon were assessed after STC induction in the control, model, and MR groups. Fecal microbiota transplantation (FMT) was performed from STC mice into pseudo germ-free mice. Changes in the contents of substance P (SP), vasoactive intestinal peptide (VIP), and gut microbiota in STC mice and pseudo germ-free mice were assessed after FMT.<br><br>RESULTS: Compared with the control group, the model mice showed the following results: the time of the first black stool was significantly longer (0.01), the number and weight of black stools were significantly reduced within 6 h (0.05), the D-xylose content in the serum was significantly reduced (< 0.05), the intestinal propulsion rate decreased (< 0.01), the content of VIP in colon tissue significantly increased (< 0.05), and SP content in the colon tissue significantly decreased (< 0.01); moreover, the colon showed significant inflame-mation and injury. Furthermore, the abundance of Firmicutes was increased, the abundance of Bacteroides decreased, and the abundance of decreased, while the abundance of the conditional pathogenic bacteria and Klebsiella increased. However, after treatment with MR, the time of the first black stool decreased (0.01), the number of black stools within 6 h increased, and the intestinal propulsion rate increased (< 0.05). Moreover, the content of D-xylose in the serum and the content of VIP in colon tissue significantly decreased (< 0.05), the content of SP in colon tissue significantly increased (< 0.01), and colon inflammation significantly improved. Additionally, the abundance of Firmicutes decreased, and the abundance of Bacteroides increased. The abundance of increased, and the abundance of decreased. In the model + FMT group, compared with control + FMT group, the content of VIP in colon tissue decreased (< 0.05), the content of SP in colon tissue significantly increased (< 0.01), and the abundance of probiotics, such as , decreased. In the MR + FMT group, compared with the model + FMT group, the content of VIP in colon tissue increased, the content of SP in colon tissue significantly decreased (< 0.01), and the abundance of probiotics increased.<br><br>CONCLUSIONS: STC mice with spleen deficiency show a decreased abundance of beneficial bacteria, such as , and an increased abundance of the conditional pathogenic bacteria . Furthermore, the mechanism of action of MR in treating STC may involve the regulation of intestinal movement, reduction of intestinal inflammation, elevation of intestinal absorption, and regulation of gut microbiota.}, }
@article {pmid35609771, year = {2022}, author = {Li, M and Guo, W and Dong, Y and Wang, W and Tian, C and Zhang, Z and Yu, T and Zhou, H and Gui, Y and Xue, K and Li, J and Jiang, F and Sarapultsev, A and Wang, H and Zhang, G and Luo, S and Fan, H and Hu, D}, title = {Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {20}, number = {2}, pages = {288-303}, pmid = {35609771}, issn = {2210-3244}, mesh = {Mice ; Animals ; *Colitis, Ulcerative/chemically induced/drug therapy ; *Gastrointestinal Microbiome ; Dextran Sulfate/adverse effects ; RNA, Ribosomal, 16S/genetics ; *Colitis/drug therapy/metabolism ; Anti-Inflammatory Agents/adverse effects ; Inflammation ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR exerts the protective effects. We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation. CSR administration significantly ameliorated the dextran sodium sulfate (DSS)-induced colitis in mice, which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index (DAI) score and intestinal permeability. Meanwhile, CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels, and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis. Notably, all the therapeutic effects were exerted in a gut microbiota-dependent manner. Furthermore, CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites, which is probably associated with the gut microbiota-mediated protective effects. In conclusion, this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.}, }
@article {pmid35606800, year = {2022}, author = {Sun, Y and Sun, P and Hu, Y and Shan, L and Geng, Q and Gong, Y and Fan, H and Zhang, T and Zhou, Y}, title = {Elevated testicular apoptosis is associated with elevated sphingosine driven by gut microbiota in prediabetic sheep.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {121}, pmid = {35606800}, issn = {1741-7007}, mesh = {Animals ; Apoptosis ; *Gastrointestinal Microbiome ; Humans ; Male ; *Melatonin ; Mice ; *Prediabetic State/complications ; Sheep ; Sphingosine ; Testis ; }, abstract = {BACKGROUND: Men with prediabetes often exhibit concomitant low-quality sperm production or even infertility, problems which urgently require improved therapeutic options. In this study, we have established a sheep model of diet-induced prediabetes that is associated with spermatogenic defects and have explored the possible underlying metabolic causes.<br><br>RESULTS: We compared male sheep fed a normal diet with those in which prediabetes was induced by a rich diet and with a third group in which the rich diet was supplemented by melatonin. Only the rich diet group had symptoms of prediabetes, and in these sheep, we found impaired spermatogenesis characterized by a block in the development of round spermatids and an increased quantity of testicular apoptotic cells. Comparing the gut microbiomes and intestinal digest metabolomes of the three groups revealed a distinctive difference in the taxonomic composition of the microbiota in prediabetic sheep, and an altered metabolome, whose most significant feature was altered sphingosine metabolism; elevated sphingosine was also found in blood and testes. Administration of melatonin alleviated the symptoms of prediabetes, including those of impaired spermatogenesis, while restoring a more normal microbiota and metabolic levels of sphingosine. Fecal microbiota transplantation from prediabetic sheep induced elevated sphingosine levels and impaired spermatogenesis in recipient mice, indicating a causal role of gut microbiota in these phenotypes.<br><br>CONCLUSIONS: Our results point to a key role of sphingosine in the disruption of spermatogenesis in prediabetic sheep and suggest it could be a useful disease marker; furthermore, melatonin represents a potential prebiotic agent for the treatment of male infertility caused by prediabetes.}, }
@article {pmid35604764, year = {2022}, author = {Benítez-Páez, A and Hartstra, AV and Nieuwdorp, M and Sanz, Y}, title = {Species- and strain-level assessment using rrn long-amplicons suggests donor's influence on gut microbial transference via fecal transplants in metabolic syndrome subjects.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2078621}, pmid = {35604764}, issn = {1949-0984}, mesh = {Bacteria/genetics ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; Humans ; *Metabolic Syndrome/microbiology/physiopathology/therapy ; Nucleotides ; }, abstract = {Fecal microbiota transplantation (FMT) is currently used for treating Clostridium difficile infection and explored for other clinical applications in experimental trials. However, the effectiveness of this therapy could vary, and partly depend on the donor's bacterial species engraftment, whose evaluation is challenging because there are no cost-effective strategies for accurately tracking the microbe transference. In this regard, the precise identification of bacterial species inhabiting the human gut is essential to define their role in human health unambiguously. We used Nanopore-based device to sequence bacterial rrn operons (16S-ITS-23S) and to reveal species-level abundance changes in the human gut microbiota of a FMT trial. By assessing the donor and recipient microbiota before and after FMT, we further evaluated whether this molecular approach reveals strain-level genetic variation to demonstrate microbe transfer and engraftment. Strict control over sequencing data quality and major microbiota covariates was critical for accurately estimating the changes in gut microbial species abundance in the recipients after FMT. We detected strain-level variation via single-nucleotide variants (SNVs) at rrn regions in a species-specific manner. We showed that it was possible to explore successfully the donor-bacterial strain (e.g., Parabacteroides merdae) engraftment in recipients of the FMT by assessing the nucleotide frequencies at rrn-associated SNVs. Our findings indicate that the engraftment of donors' microbiota is to some extent correlated with the improvement of metabolic health in recipients and that parameters such as the baseline gut microbiota configuration, sex, and age of donors should be considered to ensure the success of FMT in humans. The study was prospectively registered at the Dutch Trial registry - NTR4488 (https://www.trialregister.nl/trial/4488).}, }
@article {pmid35601099, year = {2022}, author = {Wang, J and Zhou, X and Li, X and Guo, W and Zhu, Q and Zhu, B and Lu, Y and Zheng, X and Yang, D and Wang, B}, title = {Fecal Microbiota Transplantation Alters the Outcome of Hepatitis B Virus Infection in Mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {844132}, pmid = {35601099}, issn = {2235-2988}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Hepatitis B/therapy ; Hepatitis B virus/physiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The susceptibility of mice to hepatitis B virus (HBV) infection depends on their genetic background. The gut microbiota modulates the antiviral immune response in the liver and plays a protective role against HBV infection. However, whether HBV infection outcomes depend on the gut microbiota remains unclear. In this study, we assessed the gut microbiota composition in naïve BALB/c and C57BL/6 mice using 16S rRNA gene sequencing. The gut microbiota in BALB/c mice was depleted using broad-spectrum antibiotics (ABX) and then reconstituted with fecal microbiota from naïve BALB/c or C57BL/6 mice to evaluate the effect of fecal microbiota transplantation (FMT) on the outcomes of and immune response to HBV infection. We found that HBV infection outcomes and the gut microbiota composition differed between BALB/c and C57BL/6 mice. Commensal bacteria from the fecal microbiota selectively colonized the guts of ABX-treated BALB/c mice. Mice receiving fecal microbiota from BALB/c or C57BL/6 mice displayed different HBV infection outcomes. The fecal microbiota from C57BL/6 mice induced immune tolerance in the liver and prolonged HBV infection. In conclusion, HBV infection outcomes in mice are determined by the host genetic background and gut microbiota composition. Reconstitution of the gut microbiota by FMT can alter the susceptibility to HBV infection in mice.}, }
@article {pmid35600753, year = {2022}, author = {Singh, R and Stogios, N and Smith, E and Lee, J and Maksyutynsk, K and Au, E and Wright, DC and De Palma, G and Graff-Guerrero, A and Gerretsen, P and Müller, DJ and Remington, G and Hahn, M and Agarwal, SM}, title = {Gut microbiome in schizophrenia and antipsychotic-induced metabolic alterations: a scoping review.}, journal = {Therapeutic advances in psychopharmacology}, volume = {12}, number = {}, pages = {20451253221096525}, pmid = {35600753}, issn = {2045-1253}, abstract = {Schizophrenia (SCZ) is a severe mental disorder with high morbidity and lifetime disability rates. Patients with SCZ have a higher risk of developing metabolic comorbidities such as obesity and diabetes mellitus, leading to increased mortality. Antipsychotics (APs), which are the mainstay in the treatment of SCZ, increase the risk of these metabolic perturbations. Despite extensive research, the mechanism underlying SCZ pathophysiology and associated metabolic comorbidities remains unclear. In recent years, gut microbiota (GMB) has been regarded as a 'chamber of secrets', particularly in the context of severe mental illnesses such as SCZ, depression, and bipolar disorder. In this scoping review, we aimed to investigate the underlying role of GMB in the pathophysiology of SCZ and metabolic alterations associated with APs. Furthermore, we also explored the therapeutic benefits of prebiotic and probiotic formulations in managing SCZ and AP-induced metabolic alterations. A systematic literature search yielded 46 studies from both preclinical and clinical settings that met inclusion criteria for qualitative synthesis. Preliminary evidence from preclinical and clinical studies indicates that GMB composition changes are associated with SCZ pathogenesis and AP-induced metabolic perturbations. Fecal microbiota transplantation from SCZ patients to mice has been shown to induce SCZ-like behavioral phenotypes, further supporting the plausible role of GMB in SCZ pathogenesis. This scoping review recapitulates the preclinical and clinical evidence suggesting the role of GMB in SCZ symptomatology and metabolic adverse effects associated with APs. Moreover, this scoping review also discusses the therapeutic potentials of prebiotic/probiotic formulations in improving SCZ symptoms and attenuating metabolic alterations related to APs.}, }
@article {pmid35598286, year = {2022}, author = {Batra, M and Bhatnager, R and Kumar, A and Suneja, P and Dang, AS}, title = {Interplay between PCOS and microbiome: The road less travelled.}, journal = {American journal of reproductive immunology (New York, N.Y. : 1989)}, volume = {88}, number = {2}, pages = {e13580}, doi = {10.1111/aji.13580}, pmid = {35598286}, issn = {1600-0897}, mesh = {Female ; Humans ; *Hyperandrogenism/metabolism ; *Microbiota ; *Polycystic Ovary Syndrome/metabolism ; Reproduction ; }, abstract = {Polycystic ovarian syndrome (PCOS) is a complicated neuro-endocrinal, reproductive, and metabolic condition. It encompasses patterns such as hyperandrogenism, recurrent cysts triggered by steroidogenic functional aberrations in the ovaries, overweight, chronic inflammation, and more. The underlying cause of this heterogeneous illness is obscure, although it is suspected to be driven by a blend of environmental and hereditary factors. In recent years, the connection between the microbiome and PCOS has been acknowledged and is thought to be involved in the genesis of the syndrome's emergence. Microbiota vary in different pathological features of PCOS, and fundamental pathways linked to their involvement in the commencement of diverse clinical presentations in PCOS open up a new avenue for its management. Prebiotic, probiotic, synbiotic, and fecal-microbiota-transplant, by promoting eubiosis and nullifying the effect caused by the altered microbial profile in PCOS women, can aid in management of diverse phenotypes associated with the syndrome. These microbiota-mediated treatments improve PCOS women's metabolic, inflammatory, and hormonal profiles. However, more studies are needed to elucidate the mechanisms that drive this positive effect.}, }
@article {pmid35596224, year = {2022}, author = {Chen, H and Ye, C and Cai, B and Zhang, F and Wang, X and Zhang, J and Zhang, Z and Guo, Y and Yao, Q}, title = {Berberine inhibits intestinal carcinogenesis by suppressing intestinal pro-inflammatory genes and oncogenic factors through modulating gut microbiota.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {566}, pmid = {35596224}, issn = {1471-2407}, support = {LY21H290001//Natural Science Foundation of Zhejiang Province/ ; Z20H290002//Natural Science Foundation of Zhejiang Province/ ; 2021KY569//Medical and Health Platform Program of Zhejiang Province/ ; 2017-XK-A09//Zhejiang Provincial Project for the key discipline of Traditional Chinese Medicine/ ; 82074201//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Azoxymethane ; *Berberine/pharmacology/therapeutic use ; Carcinogenesis/metabolism ; *Colitis/pathology ; Colon/pathology ; Dextran Sulfate/toxicity ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Humans ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The role of Berberine (BBR) in colorectal cancer (CRC) and gut microbiota has begun to appreciate. However, there was no direct evidence confirm that the gut microbiota regulated by BBR could inhibit CRC. This report investigated the effect of stool from BBR treated subjects and its effect on CRC.<br><br>METHODS: A mouse model for CRC was developed using azoxymethane (AOM) and dextran sulfate sodium (DSS). Intestinal tissue from affected mice were used to determine the efficacy of BBR against CRC. Stool samples were collected for the 16s rRNA gene sequencing and fecal microbiota transplantation (FMT). Finally, the mechanism of gut microbiota from BBR treated mice on CRC was explored using immunohistochemistry, RNA-Sequencing, quantitative RT-PCR, and western blot analyses.<br><br>RESULTS: BBR significantly reduced intestinal tumor development. The richness of gut microbiota were notably decreased by BBR. Specifically, the relative abundance of beneficial bacteria (Roseburia, Eubacterium, Ruminococcaceae, and Firmicutes_unclassified) was increased while the level of bacteria (Odoribacter, Muribaculum, Mucispirillum, and Parasutterella) was decreased by BBR treatment. FMT experiment determined that the mice fed with stool from BBR treated AOM/DSS mice demonstrated a relatively lower abundance of macroscopic polyps and a significantly lower expression of &#x3b2;-catenin, and PCNA in intestinal tissue than mice fed with stool from AOM/DSS mice. Mechanistically, intestinal tissue obtained from mice fed with stool from BBR treated AOM/DSS mice demonstrated a decreased expression of inflammatory cytokines including interleukin 1&#x3b2; (IL-1&#x3b2;), tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), C-C motif chemokine 1 (Ccl1), Ccl6, and C-X-C motif ligand (Cxcl9). In addition, the NF-&#x3ba;B expression was greatly suppressed in mice fed with stool from BBR treated AOM/DSS mice. Real-time PCR arrays revealed a down-regulation of genes involved in cell proliferation, angiogenesis, invasiveness, and metastasis in mice fed with stool from BBR treated AOM/DSS mice.<br><br>CONCLUSIONS: Stool obtained from BBR treated AOM/DSS mice was able to increase colon length while simultaneously decreasing the density of macroscopic polyps, cell proliferation, inflammatory modulators and the expression of NF-&#x3ba;B. Therefore, it was concluded that suppression of pro-inflammatory genes and carcinogens factors by modulating gut microbiota was an important pathway for BBR to inhibit tumor growth in conventional mice.}, }
@article {pmid35595837, year = {2022}, author = {Quaranta, G and Mandrioli, J and Bibbò, S and Guarnaccia, A and Fancello, G and Simonini, C and Amedei, A and Niccolai, E and Nannini, G and Cammarota, G and Sanguinetti, M and Masucci, L}, title = {Rummeliibacillus suwonensis: First Time Isolation from Human Feces by Culturomics.}, journal = {Current microbiology}, volume = {79}, number = {7}, pages = {197}, pmid = {35595837}, issn = {1432-0991}, support = {RF-2016-02361616.//italian ministry of health/ ; }, mesh = {Aged ; Amyotrophic Lateral Sclerosis ; Feces/microbiology ; Humans ; Male ; *Planococcaceae/isolation &amp; purification ; RNA, Ribosomal, 16S ; }, abstract = {Gut microbiota is a complex ecosystem composed by trillions of microorganisms that are crucial for human health or disease status. Currently, there are two methodological options to explore its complexity: metagenomics and culturomics. Culturomics is an approach that uses multiple culture conditions (days of incubation, enrichment factors and growth temperature) and MALDI-TOF mass spectrometry for the identification of bacterial species and sequencing when this method fails. In this paper, we describe how Colturomic's protocol has allowed the first isolation in human sample of Rummeliibacillus suwonensis, a Gram positive, facultative anaerobe bacterium. The bacterium was isolated from feces of a 69 years old male with amyotrophic lateral sclerosis (ALS) recruited for a clinical trial assessing safety and efficacy of fecal microbiota transplantation in ALS. The first isolation of the microorganism dates back to 2013 from the soil of a South Korean mountain area. In this report, morphological description, biochemical characterization and antibiotic susceptibility tests were performed to outline the bacterial properties.}, }
@article {pmid35593345, year = {2022}, author = {Bashir, R and Wani, IA and Ganie, MA}, title = {Insights into New Therapeutic Approaches for the Treatment and Management of Polycystic Ovary Syndrome: An Updated Review.}, journal = {Current pharmaceutical design}, volume = {28}, number = {18}, pages = {1493-1500}, doi = {10.2174/1381612828666220518150754}, pmid = {35593345}, issn = {1873-4286}, mesh = {Animals ; Female ; *Gastrointestinal Microbiome/physiology ; Humans ; Obesity ; *Polycystic Ovary Syndrome/drug therapy/metabolism ; Reproduction ; }, abstract = {BACKGROUND: Polycystic ovary syndrome (PCOS) is a long-term, highly prevalent, complex heterogeneous, polygenic endocrine disorder characterized by both metabolic and reproductive disorders. It affects 6-23% of reproductive-age women globally.<br><br>OBJECTIVE: This review aims to facilitate an understanding of novel PCOS management approaches and highlight the results from relevant interventional animal and human studies.<br><br>METHODS: Manual search on PubMed, Cochrane, and Scopus databases was performed for relevant articles, preclinical and clinical trials based on related keywords.<br><br>RESULTS: According to a multitude of studies, PCOS has evolved over time, but a substantial lag remains in management approaches. New insights into the cross-talk between muscle, brain, fat, and ovaries pointed out new therapeutic targets. This review has highlighted the efficacy of a wide spectrum of novel therapeutic agents [Phosphodiesterase-4 Inhibitors, Glucagon-like peptide-1 receptor agonists, nutritional supplements (Vitamins D and K, omega-3, prebiotics, probiotics and synbiotics), fecal microbiota transplantation (FMT) and intestinal cytokine IL-22] as PCOS therapeutic options. These novel therapies combine anti-inflammatory, insulinsensitizing, and anti-obesity activities, along with the restoration of the gut microbiota and thus hold the potential to address the basic pathogenic mechanisms of PCOS.<br><br>CONCLUSION: Exhaustive, multicentric and multiethnic studies are vital to generating a network of normative data to better figure out the PCOS trajectory and change prognostic outcomes. Preclinical and clinical data are warranted to corroborate the new therapeutics and direct health care resources accordingly.}, }
@article {pmid35589257, year = {2022}, author = {Bajaj, JS and Ng, SC and Schnabl, B}, title = {Promises of microbiome-based therapies.}, journal = {Journal of hepatology}, volume = {76}, number = {6}, pages = {1379-1391}, pmid = {35589257}, issn = {1600-0641}, support = {R01 AA020703/AA/NIAAA NIH HHS/United States ; R21 TR003095/TR/NCATS NIH HHS/United States ; I01 BX004594/BX/BLRD VA/United States ; I01 CX001076/CX/CSRD VA/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; U01 AA026939/AA/NIAAA NIH HHS/United States ; }, mesh = {Bacteria ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Liver Diseases ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {Humans harbour large quantities of microbes, including bacteria, fungi, viruses and archaea, in the gut. Patients with liver disease exhibit changes in the intestinal microbiota and gut barrier dysfunction. Preclinical models demonstrate the importance of the gut microbiota in the pathogenesis of various liver diseases. In this review, we discuss how manipulation of the gut microbiota can be used as a novel treatment approach for liver disease. We summarise current data on untargeted approaches, including probiotics and faecal microbiota transplantation, and precision microbiome-centered therapies, including engineered bacteria, postbiotics and phages, for the treatment of liver diseases.}, }
@article {pmid35587527, year = {2022}, author = {Yan, S and Chen, J and Zhu, L and Guo, T and Qin, D and Hu, Z and Han, S and Zhou, Y and Akan, OD and Wang, J and Luo, F and Lin, Q}, title = {Oryzanol Attenuates High Fat and Cholesterol Diet-Induced Hyperlipidemia by Regulating the Gut Microbiome and Amino Acid Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {70}, number = {21}, pages = {6429-6443}, doi = {10.1021/acs.jafc.2c00885}, pmid = {35587527}, issn = {1520-5118}, mesh = {Amino Acids/metabolism ; Animals ; Cholesterol/metabolism ; Cholesterol, LDL/metabolism ; Cricetinae ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; *Hyperlipidemias/drug therapy/etiology ; Hypolipidemic Agents/pharmacology ; Lipid Metabolism ; Liver/metabolism ; *Metabolic Diseases/metabolism ; Phenylpropionates ; }, abstract = {Hyperlipidemia is intricately associated with the dysregulation of gut microbiota and host metabolomes. This study explored the antihyperlipidemic function of oryzanol and investigated whether the function of oryzanol affected the gut microbiome and its related metabolites. Hamsters were fed a standard diet (Control) and a high fat and cholesterol (HFCD) diet with or without oryzanol, separately. Our results showed that oryzanol significantly decreased HFCD-induced fat accumulation, serum total cholesterol, low-density lipoprotein cholesterol (LDL-c), LDL-c/HDL-c ratio, triglyceride, and liver steatohepatitis, attenuated HFCD-induced gut microbiota alterations, and altered amino acid concentrations in feces and the liver. We investigated the role of the gut microbiota in the observed beneficial effects; the protective effects of oryzanol were partly diminished by suppressing the gut bacteria of hamsters after using antibiotics. A fecal microbiota transplantation experiment was carried out by transplanting the feces from HFCD group hamsters or hamsters given oryzanol supplementation (as a donor hamster). Our results showed that administering the fecal liquid from oryzanol-treated hamsters attenuated HFCD-induced hyperlipidemia, significantly decreased the abundance of norank_f__Erysipelotrichaceae, norank_f__Eubacteriaceae, and norank_f__Oscillospiraceae and the concentration of tyrosine. These outcomes are significantly positively correlated with serum lipid concentration. This study illustrated that gut microbiota is the target of oryzanol in the antihyperlipidemic effect.}, }
@article {pmid35587465, year = {2022}, author = {Doctor, MB and Basu, S}, title = {Lacrimal Gland Insufficiency in Aqueous Deficiency Dry Eye Disease: Recent Advances in Pathogenesis, Diagnosis, and Treatment.}, journal = {Seminars in ophthalmology}, volume = {37}, number = {7-8}, pages = {801-812}, doi = {10.1080/08820538.2022.2075706}, pmid = {35587465}, issn = {1744-5205}, mesh = {Humans ; *Lacrimal Apparatus ; *Dry Eye Syndromes/diagnosis/etiology/therapy ; Tears/chemistry ; Interferometry ; Stem Cell Transplantation ; }, abstract = {BACKGROUND: Aqueous deficiency dry eye disease is a chronic and potentially sight-threatening condition, that occurs due to the dysfunction of the lacrimal glands. The aim of this review was to describe the various recent developments in the understanding, diagnosis and treatment of lacrimal gland insufficiency in aqueous deficiency dry eye disease.<br><br>METHODS: A MEDLINE database search using PubMed was performed using the keywords: "dry eye disease/syndrome", "aqueous deficient/deficiency dry eye disease", "lacrimal gland" and "Sjogren's syndrome". After scanning through 750 relevant abstracts, 73 eligible articles published in the English language from 2016 to 2021 were included in the review.<br><br>RESULTS: Histopathological and ultrastructural studies have revealed new insights into the pathogenesis of cicatrising conjunctivitis-induced aqueous deficiency, where the lacrimal gland acini remain uninvolved and retain their secretory property, while significant ultrastructural changes in the gland have been observed. Recent advances in diagnosis include the techniques of direct clinical assessment of the lacrimal gland morphology and secretion, tear film osmolarity, tear film lysozyme and lactoferrin levels, tear film interferometry and lacrimal gland confocal microscopy. Developments in the treatment of aqueous deficiency dry eye disease, apart from the nanoparticle-based tear substitutes, include secretagogues like diquafosol tetrasodium and rebamipide, anti-inflammatory topical agents like nanomicellar form of cyclosporine and lifitegrast, scleral contact lenses, neurostimulation, and acupuncture for increasing the amount of tear production, minor salivary gland transplantation, faecal microbial transplantation, lacrimal gland regeneration and mesenchymal stem cell therapy.<br><br>CONCLUSIONS: Significant advances in the understanding, diagnosis and management of lacrimal gland insufficiency and its role in aqueous deficiency dry eye disease have taken place within the second half of the last decade. Of which, translational breakthroughs in terms of newer drug formulations and regenerative medicine are most promising.}, }
@article {pmid35587276, year = {2022}, author = {Pearson, JA and Ding, H and Hu, C and Peng, J and Galuppo, B and Wong, FS and Caprio, S and Santoro, N and Wen, L}, title = {IgM-associated gut bacteria in obesity and type 2 diabetes in C57BL/6 mice and humans.}, journal = {Diabetologia}, volume = {65}, number = {8}, pages = {1398-1411}, pmid = {35587276}, issn = {1432-0428}, support = {R01 HD028016/HD/NICHD NIH HHS/United States ; R01 DK114504/DK/NIDDK NIH HHS/United States ; R01 DK111038/DK/NIDDK NIH HHS/United States ; P30 DK045735/DK/NIDDK NIH HHS/United States ; MR/T010525/1/MRC_/Medical Research Council/United Kingdom ; UL1 TR001863/TR/NCATS NIH HHS/United States ; MR/K021141/1/MRC_/Medical Research Council/United Kingdom ; M01 RR000125/RR/NCRR NIH HHS/United States ; R01 HD097808/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; Animals ; Bacteria/genetics ; Child ; *Diabetes Mellitus, Type 2 ; Diet, High-Fat ; Humans ; Immunoglobulin M ; Mice ; Mice, Inbred C57BL ; Obesity/microbiology ; RNA, Ribosomal, 16S/genetics ; Weight Gain ; }, abstract = {AIMS/HYPOTHESIS: IgM is the primary antibody produced by B cells and we hypothesise that IgM antibodies to gut microbiota may play a role in immunometabolism in obesity and type 2 diabetes. To test our hypothesis, we used B6 mice deficient in activation-induced cytidine deaminase (Aid[-/-] [also known as Aicda[-/-]]) which secrete only IgM antibodies, and human faecal samples.<br><br>METHODS: We studied the immunometabolic effects and gut microbial changes in high-fat-diet-induced obesity (HFDIO) in Aid[-/-] B6 mice compared with wild-type mice. To determine similarities between mice and humans, human stool samples were collected from children and adolescents who were obese with normal glucose tolerance (NGT), obese with glucose intolerance (IGT), or obese and newly diagnosed with type 2 diabetes, for faecal microbiota transplant (FMT) into germ-free (GF) B6 mice and we assessed IgM-bound bacteria and immune responses.<br><br>RESULTS: Compared with wild-type mice, Aid[-/-] B6 mice developed exacerbated HFDIO due to abundant levels of IgM. FMT from Aid[-/-] B6 to GF B6 mice promoted greater weight gain in recipient mice compared with FMT using wild-type mouse faecal microbiota. Obese youth with type 2 diabetes had more IgM-bound gut bacteria. Using the stools from the obese youth with type 2 diabetes for FMT to GF B6 mice, we observed that the gut microbiota promoted body weight gain and impaired glucose tolerance in the recipient GF B6 mice. Importantly, some clinical features of these obese young individuals were mirrored in the GF B6 mice following FMT.<br><br>CONCLUSIONS/INTERPRETATION: Our results suggest that IgM-bound gut microbiota may play an important role in the immuno-pathogenesis of obesity and type 2 diabetes, and provide a novel link between IgM in obesity and type 2 diabetes in both mice and humans.<br><br>DATA AVAILABILITY: The 16s rRNA sequencing datasets supporting the current study have been deposited in the NCBI SRA public repository (https://www.ncbi.nlm.nih.gov/sra ; accession no. SAMN18796639).}, }
@article {pmid35585088, year = {2022}, author = {Yan, J and Liao, C and Taylor, BP and Fontana, E and Amoretti, LA and Wright, RJ and Littmann, ER and Dai, A and Waters, N and Peled, JU and Taur, Y and Perales, MA and Siranosian, BA and Bhatt, AS and van den Brink, MRM and Pamer, EG and Schluter, J and Xavier, JB}, title = {A compilation of fecal microbiome shotgun metagenomics from hematopoietic cell transplantation patients.}, journal = {Scientific data}, volume = {9}, number = {1}, pages = {219}, pmid = {35585088}, issn = {2052-4463}, support = {U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R56 AI137269/AI/NIAID NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; }, mesh = {*Feces/microbiology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Metagenomics ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Hospitalized patients receiving hematopoietic cell transplants provide a unique opportunity to study the human gut microbiome. We previously compiled a large-scale longitudinal dataset of fecal microbiota and associated metadata, but we had limited that analysis to taxonomic composition of bacteria from 16S rRNA gene sequencing. Here we augment those data with shotgun metagenomics. The compilation amounts to a nested subset of 395 samples compiled from different studies at Memorial Sloan Kettering. Shotgun metagenomics describes the microbiome at the functional level, particularly in antimicrobial resistances and virulence factors. We provide accession numbers that link each sample to the paired-end sequencing files deposited in a public repository, which can be directly accessed by the online services of PATRIC to be analyzed without the users having to download or transfer the files. Then, we show how shotgun sequencing enables the assembly of genomes from metagenomic data. The new data, combined with the metadata published previously, enables new functional studies of the microbiomes of patients with cancer receiving bone marrow transplantation.}, }
@article {pmid35584163, year = {2022}, author = {Benech, N and Galperine, T and Sokol, H and , }, title = {SER-109 for Recurrent Clostridioides difficile Infection.}, journal = {The New England journal of medicine}, volume = {386}, number = {20}, pages = {1956-1957}, doi = {10.1056/NEJMc2202493}, pmid = {35584163}, issn = {1533-4406}, mesh = {*Clostridioides difficile ; *Clostridium Infections/drug therapy ; Humans ; *Microbiota ; }, }
@article {pmid35583791, year = {2022}, author = {Pavan, S and Prabhu, AN and Prasad Gorthi, S and Das, B and Mutreja, A and Shetty, V and Ramamurthy, T and Ballal, M}, title = {Exploring the multifactorial aspects of Gut Microbiome in Parkinson's Disease.}, journal = {Folia microbiologica}, volume = {67}, number = {5}, pages = {693-706}, pmid = {35583791}, issn = {1874-9356}, mesh = {Antiparkinson Agents ; Brain ; *Gastrointestinal Microbiome/physiology ; Humans ; *Parkinson Disease/therapy ; alpha-Synuclein/metabolism ; }, abstract = {Advanced research in health science has broadened our view in approaching and understanding the pathophysiology of diseases and has also revolutionised diagnosis and treatment. Ever since the establishment of Braak's hypothesis in the propagation of alpha-synuclein from the distant olfactory and enteric nervous system towards the brain in Parkinson's Disease (PD), studies have explored and revealed the involvement of altered gut microbiota in PD. This review recapitulates the gut microbiome associated with PD severity, duration, motor and non-motor symptoms, and antiparkinsonian treatment from recent literature. Gut microbial signatures in PD are potential predictors of the disease and are speculated to be used in early diagnosis and treatment. In brief, the review also emphasises on implications of the prebiotic, probiotic, faecal microbiota transplantation, and dietary interventions as alternative treatments in modulating the disease symptoms in PD.}, }
@article {pmid35582299, year = {2022}, author = {Damiris, K and Aghaie Meybodi, M and Niazi, M and Pyrsopoulos, N}, title = {Hepatitis E in immunocompromised individuals.}, journal = {World journal of hepatology}, volume = {14}, number = {3}, pages = {482-494}, pmid = {35582299}, issn = {1948-5182}, abstract = {Hepatitis E virus (HEV) originally identified as a cause of acute icteric hepatitis in developing countries has grown to be a cause of zoonotic viral hepatitis in developed countries such as the United States. While there are eight identified genotypes to date, genotype 1 (HEV1), HEV2, HEV3, HEV4 are the most common to infect humans. HEV1 and HEV2 are most common in developing countries including Latina America, Africa and Asia, and are commonly transmitted through contaminated water supplies leading to regional outbreaks. In contrast HEV3 and HEV4 circulate freely in many mammalian animals and can lead to occasional transmission to humans through fecal contamination or consumption of undercooked meat. The incidence and prevalence of HEV in the United States is undetermined given the absence of FDA approved serological assays and the lack of commercially available testing. In majority of cases, HEV infection is a self-limiting hepatitis requiring only symptomatic treatment. However, this is not the case in immunocompromised individuals, including those that have undergone solid organ or stem cell transplantation. In this subset of patients, chronic infection can be life threatening as hepatic insult can lead to inflammation and fibrosis with subsequent cirrhosis and death. The need for re-transplantation as a result of post-transplant hepatitis is of great concern. In addition, there have been many reported incidents of extrahepatic manifestations, for which the exact mechanisms remain to be elucidated. The cornerstone of treatment in immunocompromised solid organ transplant recipients is reduction of immunosuppressive therapies, while attempting to minimize the risk of organ rejection. Subsequent treatment options include ribavirin, and pegylated interferon alpha in those who have demonstrated ribavirin resistance. Further investigation assessing safety and efficacy of anti-viral therapy is imperative given the rising global health burden. Given this concern, vaccination has been approved in China with other investigations underway throughout the world. In this review we introduce the epidemiology, diagnosis, clinical manifestations, and treatment of HEV, with emphasis on immunocompromised individuals in the United States.}, }
@article {pmid35580364, year = {2022}, author = {Thakur, S and Sheppard, JD}, title = {Gut Microbiome and Its Influence On Ocular Surface and Ocular Surface Diseases.}, journal = {Eye &amp; contact lens}, volume = {48}, number = {7}, pages = {278-282}, doi = {10.1097/ICL.0000000000000905}, pmid = {35580364}, issn = {1542-233X}, mesh = {Ecosystem ; *Eye Diseases/prevention &amp; control ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {The gut microbiome plays a substantial immunologic and pathophysiologic role in maintaining the health of the host, and dysregulation of this dynamic ecosystem has been associated with several inflammatory conditions. Many studies have explored the influence of gut microbiota on the ocular surface and whether gut microbiota impact the pathophysiology of ophthalmic conditions. These findings have highlighted the advantages of enhancing gut microbes through probiotics, prebiotics, diet, vitamin supplementations, and fecal microbial transplant in clinical practice. The purpose of this review article was to provide an up-to-date overview of the knowledge on this topic. Further exploration of this area of research is important to help guide new therapeutic targets to develop treatment and prevention of certain ocular surface diseases.}, }
@article {pmid35579969, year = {2022}, author = {Kim, YJ and Lee, JY and Lee, JJ and Jeon, SM and Silwal, P and Kim, IS and Kim, HJ and Park, CR and Chung, C and Han, JE and Choi, JW and Tak, EJ and Yoo, JH and Jeong, SW and Kim, DY and Ketphan, W and Kim, SY and Jhun, BW and Whang, J and Kim, JM and Eoh, H and Bae, JW and Jo, EK}, title = {Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2073132}, pmid = {35579969}, issn = {1949-0984}, support = {R21 AI139386/AI/NIAID NIH HHS/United States ; R56 AI143870/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Arginine ; *Gastrointestinal Microbiome ; Humans ; Lung ; Mice ; *Mycobacterium Infections, Nontuberculous/drug therapy/microbiology ; RNA, Ribosomal, 16S ; }, abstract = {Nontuberculous mycobacterial pulmonary diseases (NTM-PDs) are emerging as global health threats with issues of antibiotic resistance. Accumulating evidence suggests that the gut-lung axis may provide novel candidates for host-directed therapeutics against various infectious diseases. However, little is known about the gut-lung axis in the context of host protective immunity to identify new therapeutics for NTM-PDs. This study was performed to identify gut microbes and metabolites capable of conferring pulmonary immunity to NTM-PDs. Using metabolomics analysis of sera from NTM-PD patients and mouse models, we showed that the levels of l-arginine were decreased in sera from NTM-PD patients and NTM-infected mice. Oral administration of l-arginine significantly enhanced pulmonary antimicrobial activities with the expansion of IFN-γ-producing effector T cells and a shift to microbicidal (M1) macrophages in the lungs of NTM-PD model mice. Mice that received fecal microbiota transplants from l-arginine-treated mice showed increased protective host defense in the lungs against NTM-PD, whereas l-arginine-induced pulmonary host defense was attenuated in mice treated with antibiotics. Using 16S rRNA sequencing, we further showed that l-arginine administration resulted in enrichment of the gut microbiota composition with Bifidobacterium species. Notably, oral treatment with either Bifidobacterium pseudolongum or inosine enhanced antimicrobial pulmonary immune defense against NTM infection, even with multidrug-resistant clinical NTM strains. Our findings indicate that l-arginine-induced gut microbiota remodeling with enrichment of B. pseudolongum boosts pulmonary immune defense against NTM infection by driving the protective gut-lung axis in vivo.}, }
@article {pmid35579462, year = {2022}, author = {Renu, S and Deblais, L and Patil, V and Schrock, J and Kathayat, D and Srivastava, V and Feliciano-Ruiz, N and Han, Y and Ramesh, A and Lakshmanappa, YS and Ghimire, S and Dhakal, S and Rajashekara, G and Renukaradhya, GJ}, title = {Gut Microbiota of Obese Children Influences Inflammatory Mucosal Immune Pathways in the Respiratory Tract to Influenza Virus Infection: Optimization of an Ideal Duration of Microbial Colonization in a Gnotobiotic Pig Model.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0267421}, pmid = {35579462}, issn = {2165-0497}, mesh = {Animals ; Bifidobacterium ; Child ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Inflammation Mediators ; *Influenza, Human ; Lactobacillus ; Mice ; *Orthomyxoviridae ; *Pediatric Obesity ; Respiratory System ; Swine ; }, abstract = {The impact of obesity on the human microbiota, immune maturation, and influenza virus infection has not been yet established in natural host animal models of influenza. In this study, gnotobiotic (Gn) pigs were colonized with human fecal microbiota (HFM) of obese (oHFM) or healthy lean (hHFM) children and infected at different periods (2-, 3-, and 5-weeks post-transplantation) using a zoonotic influenza virus strain. The infected oHFM pigs were characterized by lower levels of Firmicutes (Lactococcus, Lactobacillus, Turicibacter, and Streptococcus) and Actinobacteria (Bifidobacterium), which was associated with higher levels of Proteobacteria (Klebsiella), Bacteroidetes, and Verrucomicrobia (Akkermansia) compared with the infected hHFM group (P < 0.01). Furthermore, these genera significantly correlated with the expression of immune effectors, immune regulators, and inflammatory mediators, and displayed opposite trends between oHFM and hHFM groups (P < 0.01). The lymphoid and myeloid immune cell frequencies were differently modulated by the oHFM and hHFM colonization, especially apparent in the 5-weeks HFM colonized piglets. In addition, oHFM group had higher pro-inflammatory cytokines (IL-6, IL-12, TNF-α, and IFNγ) gene expression in the respiratory tract compared with the hHFM colonized pigs was detected. In conclusion, pigs colonized for longer duration, established oHFM increased the immune maturation favoring the activation of inflammatory mediators, however, the influenza virus load remained comparable with the hHFM group. Further, a longer duration of microbial colonization (5 weeks) may be required to reveal the impact of microbiome on the host immune maturation and susceptibility to influenza virus infection in the humanized Gn pig model. IMPORTANCE The diversity of gut microbiome of obese people differs markedly from that of lean healthy individuals which, in turn, influences the severity of inflammatory diseases because of differential maturation of immune system. The mouse model provides crucial insights into the mechanism(s) regulating the immune systems mediated by the gut microbiota but its applicability to humans is questionable because immune cells in mice are poorly activated in microbiota humanized mice. Several important strains of Bifidobacterium, Lactobacillus, and Clostridium fails to colonize the murine gut. Thus, understanding the role of certain important commensal gut bacterial species influences upon health and disease, a suitable large animal model like pig that supports the growth and colonization of most of the important human gut bacteria and possess comparable immunology and physiology to humans is beneficial to improve health.}, }
@article {pmid35578339, year = {2022}, author = {Liang, L and Yang, C and Liu, L and Mai, G and Li, H and Wu, L and Jin, M and Chen, Y}, title = {Commensal bacteria-derived extracellular vesicles suppress ulcerative colitis through regulating the macrophages polarization and remodeling the gut microbiota.}, journal = {Microbial cell factories}, volume = {21}, number = {1}, pages = {88}, pmid = {35578339}, issn = {1475-2859}, support = {2021M700065//Postdoctoral Research Foundation of China/ ; 81770529//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Clostridium butyricum/genetics ; *Colitis/chemically induced ; *Colitis, Ulcerative/chemically induced/therapy ; Colon ; Cytokines ; Dextran Sulfate/adverse effects/metabolism ; Disease Models, Animal ; *Extracellular Vesicles ; *Gastrointestinal Microbiome ; Macrophages ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The extracellular vesicles (EVs) traffic constitutes an essential pathway of cellular communication. And the molecules in EVs produced by procaryotes help in maintaining homeostasis, addressing microbial imbalance and infections, and regulating the immune system. Despite the fact that Clostridium butyricum (C. butyricum) is commonly used for treating ulcerative colitis (UC), the potential role of C. butyricum-secreted EVs in commensals-host crosstalk remains unclear.<br><br>RESULTS: Here, we performed flow cytometry, western blot, immunohistochemistry and 16S rRNA analysis to explore the role of C. butyricum-derived EVs on macrophage polarization and gut microbiota composition in a dextran sulfate sodium (DSS)-induced UC mouse model. The antibiotic cocktail-induced microbiome depletion and faecal transplantations were used to further investigate the mechanisms by which EVs regulate macrophage balance. Our findings showed that C. butyricum-derived EVs improved the remission of murine colitis and polarized the transformation of macrophages to the M2 type. Furthermore, C. butyricum-derived EVs restored gut dysbiosis and altered the relative abundance of Helicobacter, Escherichia-Shigella, Lactobacillus, Akkermansia and Bacteroides, which, in turn, faecal transplantations from EVs-treated mice relieved the symptoms of UC and improved the impact of EVs on the reprogramming of the M2 macrophages.<br><br>CONCLUSION: C. butyricum-derived EVs could protect against DSS-induced colitis by regulating the repolarization of M2 macrophages and remodelling the composition of gut microbiota, suggesting the potential efficacy of EVs from commensal and probiotic Clostridium species against UC.}, }
@article {pmid35577712, year = {2022}, author = {Piawah, S and Walker, EJ and Van Blarigan, EL and Atreya, CE}, title = {The Gut Microbiome in Colorectal Cancer.}, journal = {Hematology/oncology clinics of North America}, volume = {36}, number = {3}, pages = {491-506}, doi = {10.1016/j.hoc.2022.03.001}, pmid = {35577712}, issn = {1558-1977}, mesh = {*Colorectal Neoplasms/therapy ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {The gut microbiome is important in human health and disease. Recent studies have begun to elucidate its specific role in colorectal cancer. The gut microbiome seems to play an integral role in colorectal cancer initiation and progression, and oncologic drug metabolism and toxicity. This review examines the associations between the gut microbiome and colorectal cancer initiation, progression, and oncologic drug metabolism, highlighting proposed mechanisms and landmark publications in this field. It also discusses potential methods of modulating the gut microbiome, underscoring the gaps in current understanding, and ends with a clinically relevant overview of microbiome research considerations and study design.}, }
@article {pmid35576458, year = {2022}, author = {Lu, G and Wang, W and Li, P and Wen, Q and Cui, B and Zhang, F}, title = {Washed preparation of faecal microbiota changes the transplantation related safety, quantitative method and delivery.}, journal = {Microbial biotechnology}, volume = {15}, number = {9}, pages = {2439-2449}, pmid = {35576458}, issn = {1751-7915}, mesh = {*Colitis, Ulcerative/etiology/therapy ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Humans ; *Microbiota ; Retrospective Studies ; Treatment Outcome ; }, abstract = {The safety, quantitative method and delivery of faecal microbiota transplantation (FMT) vary a lot from different countries in practice. Recently, the improved methodology of FMT based on the automatic filtration, washing process and the related delivery was named as washed microbiota transplantation (WMT). First, this study aimed to describe the methodology development of FMT from manual to washing preparation from 2012 to 2021 in China Microbiota Transplantation System (CMTS), a centralized stool bank for providing a national non-profit service. The secondary aim is to describe donor screenings, the correlation between faecal weight and treatment doses, incidence of adverse events and delivery decision. The retrospective analysis on the prospectively recorded data was performed. Results showed that the success rate of donor screening was 3.1% (32/1036). The incidence rate of fever decreased significantly from 19.4% (6/31) in manual FMT to 2.7% (24/902) in WMT in patients with ulcerative colitis (UC), which made UC a considerable disease model to reflect the quality control of faecal microbiota preparation. We defined one treatment unit as 10 cm[3] microbiota precipitation (1.0 × 10[13] bacteria) based on enriched microbiota instead of rough faecal weight. For delivering microbiota, colonic transendoscopic enteral tube is a promising way especially for multiple WMTs or frequent colonic administration of drugs combined with WMT. This study should help improve the better practice of FMT for helping more patients in the future.}, }
@article {pmid35574751, year = {2022}, author = {Yan, Y and Peng, X and Chen, Y}, title = {[Fecal microbiota transplantation in the treatment of acute intestinal pseudo obstruction secondary to intracerebral hemorrhage: a case report and literature review].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {34}, number = {3}, pages = {306-310}, doi = {10.3760/cma.j.cn121430-20220225-00179}, pmid = {35574751}, issn = {2095-4352}, mesh = {Bacteria ; Cerebral Hemorrhage/complications/therapy ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Humans ; *Intestinal Pseudo-Obstruction ; Treatment Outcome ; }, abstract = {OBJECTIVE: To analyze the clinical effects of fecal microbiota transplantation (FMT) on the treatment of acute intestinal pseudo obstruction (AIPO) secondary to intracerebral hemorrhage.<br><br>METHODS: The clinical data of a patient with AIPO secondary to intracerebral hemorrhage who was admitted to Nanfang Hospital of Southern Medical University was analyzed. The flora compositon between donor and patient was compared, finding the changes of intestinal flora before and after FMT (day 0 and day 25).<br><br>RESULTS: The main clinical findings in the patient were serious bloating, expansion of the intestinal canal and intra-abdominal hypertension. A week of conventional therapy was not effective, and the symptoms became progressively worse, affecting respiratory function.The result of fecal flora suggested the intestinal microbiota dybiosis, so FMT was attempted. After FMT, the patient's gastrointestinal symptoms were significantly relieved, and there were no further episodes within 25 days. The new result of fecal flora showed that the flora colonizing the intestine was dominated by Akkermansia and Bifidobacterium, with a significant decrease in potential pro-inflammatory and gas-producing bacteria and an increased gut microbiota diversity. The results trended to be partly consistent with the donor at 25 days after FMT: at the phylum level, the relative abundance of Bacterioidetes, Vereucomicrobia, Firmicutes and Actinobacteria were increased while Proteobacteria was decreased; at the class level, the relative abundance of Verrucomicrobiae, Bacterioidia, Actinobacteria, Coriobacteriia and Clostridia were increased and Gammaproteobacteria was decreased; at the order level, the relative abundance of Bacterioidales, Verrucomicrobiales, Clostridiale, Coriobacteriales were increased and Betaproteobacteriales, Enterobacteriales were decreased; at the family level, the relative abundance of Bifidobacteriaceae, Akkermansiaceae, Ruminococcaceae were increased and Enterobacteriaceae was decreased; at the genus level, the relative abundance of Akkermansia, Bifidobacterium were increased and Escherichia-Shigella, Klebsiella were decreased. At 1-year follow-up, the patient lived with self-care and scored 5 points in Glasgow outcome scale (GOS).<br><br>CONCLUSIONS: FMT may provide clinical benefit in treated patients with AIPO secondary to intracerebral hemorrhage, probably by regulating the intestinal microflora, and re-establishing proper intestinal barrier, to maintain intestinal homeostasis.}, }
@article {pmid35572649, year = {2022}, author = {Luo, W and Guo, S and Zhou, Y and Zhao, J and Wang, M and Sang, L and Chang, B and Wang, B}, title = {Hepatocellular Carcinoma: How the Gut Microbiota Contributes to Pathogenesis, Diagnosis, and Therapy.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {873160}, pmid = {35572649}, issn = {1664-302X}, abstract = {The gut microbiota is gaining increasing attention, and the concept of the "gut-liver axis" is gradually being recognized. Leaky gut resulting from injury and/or inflammation can cause the translocation of flora to the liver. Microbiota-associated metabolites and components mediate the activation of a series of signalling pathways, thereby playing an important role in the development of hepatocellular carcinoma (HCC). For this reason, targeting the gut microbiota in the diagnosis, prevention, and treatment of HCC holds great promise. In this review, we summarize the gut microbiota and the mechanisms by which it mediates HCC development, and the characteristic alterations in the gut microbiota during HCC pathogenesis. Furthermore, we propose several strategies to target the gut microbiota for the prevention and treatment of HCC, including antibiotics, probiotics, faecal microbiota transplantation, and immunotherapy.}, }
@article {pmid35572534, year = {2022}, author = {Zhao, H and Lyu, Y and Zhai, R and Sun, G and Ding, X}, title = {Metformin Mitigates Sepsis-Related Neuroinflammation via Modulating Gut Microbiota and Metabolites.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {797312}, pmid = {35572534}, issn = {1664-3224}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; *Metformin/pharmacology/therapeutic use ; Neuroinflammatory Diseases ; RNA, Ribosomal, 16S/genetics ; Rats ; *Sepsis/metabolism ; }, abstract = {Gut microbiota affects the functions of brains. However, its mechanism in sepsis remains unclear. This study evaluated the effect of metformin on ameliorating sepsis-related neurodamage by regulating gut microbiota and metabolites in septic rats. Cecal ligation and puncture (CLP) was used to establish the sepsis-related neurodamage animal models. Metformin therapy by gavage at 1 h after CLP administration was followed by fecal microbiota transplantation (FMT) to ensure the efficacy and safety of metformin on the sepsis-related neurodamage by regulating gut microbiota. The gut microbiota and metabolites were conducted by 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry metabolomic analysis. The brain tissue inflammation response was analyzed by histopathology and reverse transcription-polymerase chain reaction (RT-PCR). This study reported brain inflammatory response, hemorrhage in sepsis-related neurodamage rats compared with the control group (C group). Surprisingly, the abundance of gut microbiota slightly increased in sepsis-related neurodamage rats than C group. The ratio of Firmicutes/Bacteroidetes was significantly increased in the CLP group than the C group. However, no difference was observed between the CLP and the metformin-treated rats (MET group). Interestingly, the abundance of Escherichia_Shigella increased in the MET group than the C and CLP groups, while Lactobacillaceae abundance decreased. Furthermore, Prevotella_9, Muribaculaceae, and Alloprevotella related to short-chain fatty acids production increased in the sepsis-related neurodamage of metformin-treated rats. Additionally, Prevotella_9 and Muribaculaceae correlated positively to 29 metabolites that might affect the inflammatory factors in the brain. The FMT assay showed that metformin improved sepsis-related neurodamage by regulating the gut microbiota and metabolites in septic rats. The findings suggest that metformin improves the sepsis-related neurodamage through modulating the gut microbiota and metabolites in septic rats, which may be an effective therapy for patients with sepsis-related neurodamage.}, }
@article {pmid35572528, year = {2022}, author = {Kawasoe, J and Uchida, Y and Kawamoto, H and Miyauchi, T and Watanabe, T and Saga, K and Tanaka, K and Ueda, S and Terajima, H and Taura, K and Hatano, E}, title = {Propionic Acid, Induced in Gut by an Inulin Diet, Suppresses Inflammation and Ameliorates Liver Ischemia and Reperfusion Injury in Mice.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {862503}, pmid = {35572528}, issn = {1664-3224}, mesh = {Animals ; Diet ; Fatty Acids, Volatile ; Inflammation/metabolism ; Inulin/pharmacology ; Ischemia/complications ; *Liver Diseases/etiology ; Mice ; Propionates/pharmacology ; *Reperfusion Injury/metabolism ; }, abstract = {Liver ischemia and reperfusion injury (IRI) is one of the obstacles in liver surgery such as liver resection and transplantation. In this study, we investigated the preventive effect on mouse liver IRI by feeding mice with inulin, which is a heterogeneous blend of indigestible fructose polymer. Mice were fed either a control ordinary diet (CD) or an inulin diet (ID) containing 5% inulin in the CD, for 14 days before the ischemia and reperfusion (IR) maneuver. IR induced-liver damages were significantly ameliorated in the ID group, compared with those in the CD group. Feeding mice with an ID, but not a CD, elevated levels of Bacteroidetes among gut microbiota, and especially increased Bacteroides acidifaciens in mouse feces, which resulted in significant elevation of short-chain fatty acids (SCFAs) in the portal vein of mice. Among SCFAs, propionic acid (PA) was most significantly increased. The microbial gene functions related to PA biosynthesis were much higher in the fecal microbiome of the ID group compared to the CD. However, the action of PA on liver IRI has not been yet clarified. Direct intraperitoneal administration of PA alone prior to the ischemia strongly suppressed liver cell damages as well as inflammatory responses caused by liver IR. Furthermore, PA suppressed the secretion of inflammatory cytokines from peritoneal macrophages stimulated in vitro through TLR-4 with high-mobility group box 1 protein (HMGB-1), known to be released from apoptotic liver cells during the IR insult. The present study shows that PA may play a key role in the inulin-induced amelioration of mouse liver IRI.}, }
@article {pmid35571974, year = {2022}, author = {Al, KF and Craven, LJ and Gibbons, S and Parvathy, SN and Wing, AC and Graf, C and Parham, KA and Kerfoot, SM and Wilcox, H and Burton, JP and Kremenchutzky, M and Morrow, SA and Casserly, C and Meddings, J and Sharma, M and Silverman, MS}, title = {Fecal microbiota transplantation is safe and tolerable in patients with multiple sclerosis: A pilot randomized controlled trial.}, journal = {Multiple sclerosis journal - experimental, translational and clinical}, volume = {8}, number = {2}, pages = {20552173221086662}, pmid = {35571974}, issn = {2055-2173}, abstract = {BACKGROUND: Patients with MS have an altered gut microbiota compared to healthy individuals, as well as elevated small intestinal permeability, which may be contributing to the development and progression of the disease.<br><br>OBJECTIVE: We sought to investigate if fecal microbiota transplantation was safe and tolerable in MS patients and if it could improve abnormal intestinal permeability.<br><br>METHODS: Nine patients with MS were recruited and provided monthly FMTs for up to six months. The primary outcome investigated was change in peripheral blood cytokine concentrations. The secondary outcomes were gut microbiota composition, intestinal permeability, and safety (assessed with EDSS and MRI).<br><br>RESULTS: The study was terminated early and was subsequently underpowered to assess whether peripheral blood cytokines were altered following FMTs. FMTs were safe in this group of patients. Two of five patients had elevated small intestinal permeability at baseline that improved to normal values following FMTs. Significant, donor-specific, beneficial alterations to the MS patient gut microbiota were observed following FMT.<br><br>CONCLUSION: FMT was safe and tolerable in this cohort of RRMS patients, may improve elevated small intestinal permeability, and has the potential to enrich for an MS-protective microbiota. Further studies with longer follow-up and larger sample sizes are required to determine if FMT is a suitable therapy for MS.}, }
@article {pmid35568180, year = {2022}, author = {Chatterjee, G and Negi, S and Basu, S and Faintuch, J and O'Donovan, A and Shukla, P}, title = {Microbiome systems biology advancements for natural well-being.}, journal = {The Science of the total environment}, volume = {838}, number = {Pt 2}, pages = {155915}, doi = {10.1016/j.scitotenv.2022.155915}, pmid = {35568180}, issn = {1879-1026}, mesh = {Bacteria ; *Gastrointestinal Microbiome ; Humans ; Intestines ; *Microbiota/physiology ; Systems Biology ; }, abstract = {Throughout the years all data from epidemiological, physiological and omics have suggested that the microbial communities play a considerable role in modulating human health. The population of microorganisms residing in the human intestine collectively known as microbiota presents a genetic repertoire that is higher in magnitude than the human genome. They play an essential role in host immunity and neuronal signaling. Rapid enhancement of sequence based screening and development of humanized gnotobiotic model has sparked a great deal of interest among scientists to probe the dynamic interactions of the commensal bacteria. This review focuses on systemic analysis of the gut microbiome to decipher the complexity of the host-microbe intercommunication and gives a special emphasis on the evolution of targeted precision medicine through microbiome engineering. In addition, we have also provided a comprehensive description of how interconnection between metabolism and biochemical reactions in a specific organism can be obtained from a metabolic network or a flux balance analysis and combining multiple datasets helps in the identification of a particular metabolite. The review highlights how genetic modification of the critical components and programming the resident microflora can be employed for targeted precision medicine. Inspite of the ongoing debate on the utility of gut microbiome we have explored on the probable new therapeutic avenues like FMT (Fecal microbiota transplant) can be utilized. This review also recapitulates integrating human-relevant 3D cellular models coupled with computational models and the metadata obtained from interventional and epidemiological studies may decipher the complex interactome of diet-microbiota-disease pathophysiology. In addition, it will also open new avenues for the development of therapeutics derived from microbiome or implementation of personalized nutrition. In addition, the identification of biomarkers can also help towards the development of new diagnostic tools and eventually will lead to strategic management of the disease. Inspite of the ongoing debate on the utility of the gut microbiome we have explored how probable new therapeutic avenues like FMT (Fecal microbiota transplant) can be utilized. This review also summarises integrating human-relevant 3D cellular models coupled with computational models and the metadata obtained from interventional and epidemiological studies may decipher the complex interactome of diet- microbiota-disease pathophysiology. In addition, it will also open new avenues for the development of therapeutics derived from the microbiome or implementation of personalized nutrition. In addition, the identification of biomarkers can also help towards the development of new diagnostic tools and eventually will lead to strategic management of disease.}, }
@article {pmid35563189, year = {2022}, author = {Fan, Z and Zhang, X and Shang, Y and Zou, M and Zhou, M and E, Q and Fei, S and Chen, W and Li, J and Zhang, X and Liu, X}, title = {Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries.}, journal = {International journal of molecular sciences}, volume = {23}, number = {9}, pages = {}, pmid = {35563189}, issn = {1422-0067}, mesh = {Animals ; Cytokines ; *Diet, High-Fat/adverse effects ; Endotoxins ; Female ; *Gastrointestinal Microbiome/physiology ; Inflammation ; Macrophages ; Mice ; Mice, Inbred C57BL ; Ovary ; }, abstract = {Obesity induced by a high-fat diet (HFD) leads to the excessive consumption of primordial follicles (PFs) in the ovaries. There is systemic chronic inflammation under HFD conditions, but no previous studies have explored whether there is a certain causal relationship between HFD-induced chronic inflammation and the overactivation of PFs. Here, we showed that HFD causes disorders of intestinal microflora in mice, with five Gram-negative bacteria showing the most profound increase at the genus level compared to the normal diet (ND) groups and contributes to the production of endotoxin. Endotoxin promotes M1 macrophage infiltration in the ovaries, where they exhibit proinflammatory actions by secreting cytokines IL-6, IL-8, and TNFα. These cytokines then boost the activation of PFs by activating Signal Transducer and Activator of Transcription 3 (STAT3) signaling in follicles. Interestingly, transplantation of the HFD intestinal microflora to the ND mice partly replicates ovarian macrophage infiltration, proinflammation, and the overactivation of PFs. Conversely, transplanting the ND fecal microbiota to the HFD mice can alleviate ovarian inflammation and rescue the excessive consumption of PFs. Our findings uncover a novel and critical function of gut microbes in the process of PF overactivation under HFD conditions, and may provide a new theoretical basis for the microbial treatment of patients with premature ovarian insufficiency caused by HFD.}, }
@article {pmid35562867, year = {2022}, author = {Soriano, S and Curry, K and Wang, Q and Chow, E and Treangen, TJ and Villapol, S}, title = {Fecal Microbiota Transplantation Derived from Alzheimer's Disease Mice Worsens Brain Trauma Outcomes in Wild-Type Controls.}, journal = {International journal of molecular sciences}, volume = {23}, number = {9}, pages = {}, pmid = {35562867}, issn = {1422-0067}, support = {R21 NS106640/NS/NINDS NIH HHS/United States ; R21NS106640/NH/NIH HHS/United States ; }, mesh = {*Alzheimer Disease/pathology/therapy ; Animals ; *Brain Injuries, Traumatic/therapy ; Fecal Microbiota Transplantation/methods ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration, both of which increase the risk and accelerate the progression of Alzheimer's disease (AD). The gut microbiome is an essential modulator of the immune system, impacting the brain. AD has been related with reduced diversity and alterations in the community composition of the gut microbiota. This study aimed to determine whether the gut microbiota from AD mice exacerbates neurological deficits after TBI in control mice. We prepared fecal microbiota transplants from 18 to 24 month old 3×Tg-AD (FMT-AD) and from healthy control (FMT-young) mice. FMTs were administered orally to young control C57BL/6 (wild-type, WT) mice after they underwent controlled cortical impact (CCI) injury, as a model of TBI. Then, we characterized the microbiota composition of the fecal samples by full-length 16S rRNA gene sequencing analysis. We collected the blood, brain, and gut tissues for protein and immunohistochemical analysis. Our results showed that FMT-AD administration stimulates a higher relative abundance of the genus Muribaculum and a decrease in Lactobacillus johnsonii compared to FMT-young in WT mice. Furthermore, WT mice exhibited larger lesion, increased activated microglia/macrophages, and reduced motor recovery after FMT-AD compared to FMT-young one day after TBI. In summary, we observed gut microbiota from AD mice to have a detrimental effect and aggravate the neuroinflammatory response and neurological outcomes after TBI in young WT mice.}, }
@article {pmid35561601, year = {2022}, author = {Wang, X and Wu, X and Cong, X and Ren, J and Li, J and Zhu, J and Dai, M and Hrabchenko, N and Du, Y and Qi, J}, title = {The functional role of fecal microbiota transplantation on Salmonella Enteritidis infection in chicks.}, journal = {Veterinary microbiology}, volume = {269}, number = {}, pages = {109449}, doi = {10.1016/j.vetmic.2022.109449}, pmid = {35561601}, issn = {1873-2542}, mesh = {Animals ; Chickens ; Fecal Microbiota Transplantation/veterinary ; *Poultry Diseases/therapy ; RNA, Ribosomal, 16S/genetics ; *Salmonella Infections, Animal/therapy ; Salmonella enteritidis ; }, abstract = {The intestinal microbiota plays important roles in animal health and growth. We investigated the efficacy and mechanisms of fecal microbiota transplantation (FMT) from adult SPF chickens against Salmonella Enteritidis (SE) infection in chicks. We transplanted 160 recipient SPF chicks (1-day-old) that were randomly divided into four groups, Ca (challenge), Cb (non-challenge), Fa (FMT and challenge) and Fb (FMT without challenge). The experiment lasted 40 days. We found that FMT reduced mortality as well as liver inflammatory lesions, promoted weight gain, improved immunity, ameliorated the digestion and absorption ability and inhibited SE colonization in the liver of challenged chicks. 16S rRNA gene high-throughput sequencing indicated that SE challenge caused a significant increase in the relative abundance of Parasutterella in the cecal microbiota of the recipient chicks (P < 0.05). FMT led to the maturation of the intestinal flora of recipients and the relative abundance of the Bacteroides, Rikenellaceae_ RC9_ gut_ group, Prevotellaceae_ UCG_ 001, Prevotellaceae_ Ga6A1_ group and Parabacteroides was significantly increased (P < 0.05). FMT from adult SPF chickens regulated the intestinal microbiota of chicks and increased resistance to SE infection.}, }
@article {pmid35548572, year = {2022}, author = {Inczefi, O and Bacsur, P and Resál, T and Keresztes, C and Molnár, T}, title = {The Influence of Nutrition on Intestinal Permeability and the Microbiome in Health and Disease.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {718710}, pmid = {35548572}, issn = {2296-861X}, abstract = {The leakage of the intestinal barrier and the disruption of the gut microbiome are increasingly recognized as key factors in different pathophysiological conditions, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), chronic liver diseases, obesity, diabetes mellitus, types of cancer, and neuropsychiatric disorders. In this study, the mechanisms leading to dysbiosis and "leaky gut" are reviewed, and a short summary of the current knowledge regarding different diseases is provided. The simplest way to restore intestinal permeability and the microbiota could be ideal nutrition. Further therapeutic options are also available, such as the administration of probiotics or postbiotics or fecal microbiota transplantation.}, }
@article {pmid35548562, year = {2022}, author = {Lei, J and Dong, Y and Hou, Q and He, Y and Lai, Y and Liao, C and Kawamura, Y and Li, J and Zhang, B}, title = {Intestinal Microbiota Regulate Certain Meat Quality Parameters in Chicken.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {747705}, pmid = {35548562}, issn = {2296-861X}, abstract = {UNLABELLED: Growing evidence of intestinal microbiota-muscle axis provides a possibility to improve meat quality of broilers through regulating intestinal microbiota. Water-holding capacity is a crucial factor to evaluate the meat quality. High quality of water-holding capacity is usually described as a low drip-losing rate. This study aimed to explore the relationship between intestinal microbiota and water-holding capacity of muscle in broilers. According to our results, two native breeds of broilers (the Arbor Acres broilers and the Beijing-You broilers) exhibited remarkable differences in microbiota composition. However, the regular of gut bacteria compositions gradually became similar when the two breeds of broiler were raised in a same feeding environment. Therefore, this similar regular of intestinal microbiota induced similar water-holding capacity of the muscle from the two breeds. In subsequent fecal microbiota transplantation (FMT) experiments, the intestinal microbiota community of the Arbor Acres broilers was remodeling by oral gavage of bacterial suspension that was derived from the Beijing-You broilers. Then, not only body weight and abdominal fat rate were increased, but also drip loss of muscle was decreased in the Arbor Acres broilers. Additionally, muscle fiber diameter of biceps femoris muscle and expression of MyoD1 were notably enlarged. Muscle fiber diameter and related genes were deemed as important elements for water-holding capacity of muscle. Simultaneously, we screened typical intestinal bacteria in both the two native breeds of broilers by 16S rDNA sequencing. Lachnoclostridium was the only bacteria genus associated with drip-losing rate, meat fiber diameter, body weight, and abdominal fat rate.<br><br>IMPORTANCE: Higher body weight and superior meat quality in livestock imply an adequate source of protein and substantial commercial value. Regulating the intestinal microbiota of broilers is a promising approach to optimize commercial phenotypes. Our results indicate that the intestinal microbiota profile could be reconstructed by external factors, leading to advantageous changes in muscle characteristics. The cecum microbiota of native broilers have the ability to improve certain meat quality and production performance. The population of Lachnoclostridium spp. could be used to regulate body weight and drip-losing rate in broilers, but more study is needed.}, }
@article {pmid35546555, year = {2022}, author = {Wardill, HR and de Mooij, CEM and Da Silva Ferreira, AR and Havinga, H and Harmsen, HJM and van der Velden, WJFM and van Groningen, LFJ and Tissing, WJE and Blijlevens, NMA}, title = {Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with anakinra.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {6803}, pmid = {35546555}, issn = {2045-2322}, mesh = {Animals ; Fever/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1 ; Melphalan/therapeutic use ; *Multiple Myeloma/diagnosis ; Rats ; Tumor Microenvironment ; }, abstract = {High-dose chemotherapy causes intestinal inflammation and subsequent breakdown of the mucosal barrier, permitting translocation of enteric pathogens, clinically manifesting as fever. Antibiotics are mainstay for controlling these complications, however, they are increasingly recognized for their detrimental effects, including antimicrobial resistance and dysbiosis. Here, we show that mucosal barrier injury induced by the mucotoxic chemotherapeutic agent, high-dose melphalan (HDM), is characterized by hyper-active IL-1b/CXCL1/neutrophil signaling. Inhibition of this pathway with IL-1RA, anakinra, minimized the duration and intensity of mucosal barrier injury and accompanying clinical symptoms, including diarrhea, weight loss and fever in rats. 16S analysis of fecal microbiome demonstrated a more stable composition in rats receiving anakinra, with reduced pathogen expansion. In parallel, we report through Phase IIA investigation that anakinra is safe in stem cell transplant patients with multiple myeloma after HDM. Ramping-up anakinra (100-300 mg administered intravenously for 15 days) did not cause any adverse events or dose limiting toxicities, nor did it change time to neutrophil recovery. Our results reinforce that strengthening the mucosal barrier may be an effective supportive care strategy to mitigate local and systemic clinical consequences of HDM. We are now conducting a Phase IIB multicenter, placebo-controlled, double-blinded trial to assess clinical efficacy of anakinra (AFFECT-2).Trial registration: ClinicalTrials.gov identifier: NCT03233776.}, }
@article {pmid35545183, year = {2022}, author = {Ouyang, ZR and Niu, XR and Wang, WG and Zhao, JH}, title = {The role of short-chain fatty acids in Clostridioides difficile infection: A review.}, journal = {Anaerobe}, volume = {75}, number = {}, pages = {102585}, doi = {10.1016/j.anaerobe.2022.102585}, pmid = {35545183}, issn = {1095-8274}, mesh = {*Clostridioides difficile ; *Clostridium Infections/drug therapy ; Epithelial Cells/metabolism ; Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Clostridioides difficile is a Gram-positive, obligate anaerobic, spore-producing intestinal opportunistic pathogen. CDI outbreaks in Europe and the Americas in recent years are a major health concern. Intestinal short-chain fatty acids (SCFAs) are an important energy source for colonic epithelial cells, and the roles of SCFAs in reducing intestinal inflammation, inhibiting intestinal tumors, and regulating gut microbial homeostasis are being actively researched. Furthermore, SCFAs attenuate CDI or directly inhibit C. difficile growth through different pathways in vivo and in vitro. This review assesses the role of SCFAs in CDI and discusses the potential use of these molecules as therapeutic targets for CDI.}, }
@article {pmid35538082, year = {2022}, author = {Shin, J and Noh, JR and Choe, D and Lee, N and Song, Y and Cho, S and Kang, EJ and Go, MJ and Ha, SK and Kim, JH and Kim, YH and Kim, KS and Kim, BC and Lee, CH and Cho, BK}, title = {Comprehensive 16S rRNA and metagenomic data from the gut microbiome of aging and rejuvenation mouse models.}, journal = {Scientific data}, volume = {9}, number = {1}, pages = {197}, pmid = {35538082}, issn = {2052-4463}, support = {2019M3A9F3065867//National Research Foundation of Korea (NRF)/ ; 2018M3A9H3024759//National Research Foundation of Korea (NRF)/ ; }, mesh = {*Aging/genetics ; Animals ; Disease Models, Animal ; *Gastrointestinal Microbiome/genetics ; Metagenomics ; Mice ; *RNA, Ribosomal, 16S/genetics ; Rejuvenation ; }, abstract = {The gut microbiota is associated with the health and longevity of the host. A few methods, such as fecal microbiota transplantation and oral administration of probiotics, have been applied to alter the gut microbiome and promote healthy aging. The changes in host microbiomes still remain poorly understood. Here, we characterized both the changes in gut microbial communities and their functional potential derived from colon samples in mouse models during aging. We achieved this through four procedures including co-housing, serum injection, parabiosis, and oral administration of Akkermansia muciniphila as probiotics using bacterial 16 S rRNA sequencing and shotgun metagenomic sequencing. The dataset comprised 16 S rRNA sequencing (36,249,200 paired-end reads, 107 sequencing data) and metagenomic sequencing data (307,194,369 paired-end reads, 109 sequencing data), characterizing the taxonomy of bacterial communities and their functional potential during aging and rejuvenation. The generated data expand the resources of the gut microbiome related to aging and rejuvenation and provide a useful dataset for research on developing therapeutic strategies to achieve healthy active aging.}, }
@article {pmid35535879, year = {2022}, author = {Alsegiani, AS and Shah, ZA}, title = {The influence of gut microbiota alteration on age-related neuroinflammation and cognitive decline.}, journal = {Neural regeneration research}, volume = {17}, number = {11}, pages = {2407-2412}, pmid = {35535879}, issn = {1673-5374}, support = {R01 NS112642/NS/NINDS NIH HHS/United States ; }, abstract = {Recent emerging research on intestinal microbiota and its contribution to the central nervous system during health and disease has attracted significant attention. Age-related intestinal microbiota changes initiate brain aging and age-related neurodegenerative disorders. Aging is one of the critical predisposing risk factors for the development of neurodegenerative diseases. Maintaining a healthy gut microbiota is essential for a healthy body and aging, but dysbiosis could initiate many chronic diseases. Understanding the underlying mechanisms of gut microbiota alterations/dysbiosis will help identify biomarkers for aging-related chronic conditions. This review summarizes recent advances in microbiota-neurodegenerative disease research and will enhance our understanding of gut microbiota dysbiosis and its effects on brain aging.}, }
@article {pmid35535069, year = {2022}, author = {Philips, CA and Augustine, P}, title = {Gut Barrier and Microbiota in Cirrhosis.}, journal = {Journal of clinical and experimental hepatology}, volume = {12}, number = {2}, pages = {625-638}, pmid = {35535069}, issn = {0973-6883}, abstract = {Gut microbiota and their homeostatic functions are central to the maintenance of the intestinal mucosal barrier. The gut barrier functions as a structural, biological, and immunological barrier, preventing local and systemic invasion and inflammation of pathogenic taxa, resulting in the propagation or causation of organ-specific (liver disease) or systemic diseases (sepsis) in the host. In health, commensal bacteria are involved in regulating pathogenic bacteria, sinister bacterial products, and antigens; and help control and kill pathogenic organisms by secreting antimicrobial metabolites. Gut microbiota also participates in the extraction, synthesis, and absorption of nutrient metabolites, maintains intestinal epithelial integrity and regulates the development, homeostasis, and function of innate and adaptive immune cells. Cirrhosis is associated with local and systemic immune, vascular, and inflammatory changes directly or indirectly linked to perturbations in quality and quantity of intestinal microbiota and intestinal mucosal integrity. Dysbiosis and gut barrier dysfunction are directly involved in the pathogenesis of compensated cirrhosis and the type and severity of complications in decompensated cirrhosis, such as bacterial infections, encephalopathy, extrahepatic organ failure, and progression to acute on chronic liver failure. This paper reviews the normal gut barrier, gut barrier dysfunction, and dysbiosis-associated clinical events in patients with cirrhosis. The role of dietary interventions, antibiotics, prebiotics, probiotics, synbiotics, and healthy donor fecal microbiota transplantation (FMT) to modulate the gut microbiota for improving patient outcomes is further discussed.}, }
@article {pmid35534624, year = {2023}, author = {Miyauchi, E and Shimokawa, C and Steimle, A and Desai, MS and Ohno, H}, title = {The impact of the gut microbiome on extra-intestinal autoimmune diseases.}, journal = {Nature reviews. Immunology}, volume = {23}, number = {1}, pages = {9-23}, pmid = {35534624}, issn = {1474-1741}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *Autoimmune Diseases ; *Lupus Erythematosus, Systemic/etiology/therapy ; *Diabetes Mellitus, Type 1 ; Risk Factors ; *Intestinal Diseases ; Dysbiosis ; }, abstract = {The prevalence of autoimmune diseases (ADs) worldwide has rapidly increased over the past few decades. Thus, in addition to the classical risk factors for ADs, such as genetic polymorphisms, infections and smoking, environmental triggers have been considered. Recent sequencing-based approaches have revealed that patients with extra-intestinal ADs, such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, have distinct gut microbiota compositions compared to healthy controls. Faecal microbiota transplantation or inoculation with specific microbes in animal models of ADs support the hypothesis that alterations of gut microbiota influence autoimmune responses and disease outcome. Here, we describe the compositional and functional changes in the gut microbiota in patients with extra-intestinal AD and discuss how the gut microbiota affects immunity. Moreover, we examine how the gut microbiota might be modulated in patients with ADs as a potential preventive or therapeutic approach.}, }
@article {pmid35534496, year = {2022}, author = {Wang, R and Yang, X and Liu, J and Zhong, F and Zhang, C and Chen, Y and Sun, T and Ji, C and Ma, D}, title = {Gut microbiota regulates acute myeloid leukaemia via alteration of intestinal barrier function mediated by butyrate.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {2522}, pmid = {35534496}, issn = {2041-1723}, mesh = {Animals ; Butyrates/pharmacology ; Dysbiosis/drug therapy ; *Gastrointestinal Microbiome ; Humans ; *Leukemia, Myeloid, Acute ; Lipopolysaccharides/adverse effects ; Mice ; }, abstract = {The gut microbiota has been linked to many cancers, yet its role in acute myeloid leukaemia (AML) progression remains unclear. Here, we show decreased diversity in the gut microbiota of AML patients or murine models. Gut microbiota dysbiosis induced by antibiotic treatment accelerates murine AML progression while faecal microbiota transplantation reverses this process. Butyrate produced by the gut microbiota (especially Faecalibacterium) significantly decreases in faeces of AML patients, while gavage with butyrate or Faecalibacterium postpones murine AML progression. Furthermore, we find the intestinal barrier is damaged in mice with AML, which accelerates lipopolysaccharide (LPS) leakage into the blood. The increased LPS exacerbates leukaemia progression in vitro and in vivo. Butyrate can repair intestinal barrier damage and inhibit LPS absorption in AML mice. Collectively, we demonstrate that the gut microbiota promotes AML progression in a metabolite-dependent manner and that targeting the gut microbiota might provide a therapeutic option for AML.}, }
@article {pmid35533688, year = {2022}, author = {Joachim, A and Schwerd, T and Hölz, H and Sokollik, C and Konrad, LA and Jordan, A and Lanzersdorfer, R and Schmidt-Choudhury, A and Hünseler, C and Adam, R}, title = {[Fecal Microbiota Transfer (FMT) in Children and Adolescents - Review and statement by the GPGE microbiome working group].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {60}, number = {6}, pages = {963-969}, doi = {10.1055/a-1801-0284}, pmid = {35533688}, issn = {1439-7803}, mesh = {Adolescent ; Child ; *Clostridioides difficile ; *Clostridium Infections/complications ; Dysbiosis/complications ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; *Microbiota ; Treatment Outcome ; }, abstract = {The human microbiome and especially the gastrointestinal microbiota are associated with health and disease. Disturbance in the composition or function of fecal microbiota (dysbiosis) plays a role in the development of pediatric gastrointestinal diseases. Fecal microbiota transfer (FMT) is a special intervention, where microbiota are transferred from a healthy donor.In this review we describe the current state of knowledge for FMT in pediatric patients. There is satisfactory evidence concerning FMT in patients with recurrent C. difficile infection. For inflammatory bowel disease, few studies show a potential benefit.Adverse events occurred frequently in clinical studies, but were mostly mild and transient. There are hardly any data on long-term side effects of FMT, which are particularly significant for pediatrics. In practice, there is uncertainty as to which application route, dosage or frequency should be used. Legally, donor stool is considered a drug in German-speaking countries, for which no marketing authorization exists.In conclusion, knowledge about physiology, efficacy and side effects of FMT is insufficient and legal concerns complicate its implementation. More studies on this topic are needed urgently.}, }
@article {pmid35530905, year = {2022}, author = {Alabdaljabar, MS and Aslam, HM and Veeraballi, S and Faizee, FA and Husain, BH and Iqbal, SM and Hashmi, SK}, title = {Restoration of the Original Inhabitants: A Systematic Review on Fecal Microbiota Transplantation for Graft-Versus-Host Disease.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e23873}, pmid = {35530905}, issn = {2168-8184}, abstract = {A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD, we conducted a systemic literature search using multiple electronic databases. Upon pooling of data, 79 patients from six studies and five case reports were included. Complete remission (CR) occurred in 55.9% of patients, and partial remission (PR) occurred in 26.5% of patients (82.4% overall response rate). A limited number of patients had treatment-related mortality (TRM), while few showed mild gastrointestinal (GI)-related and non-GI adverse effects. None of the studies directly examined the role of FMT in the prevention of GVHD. In conclusion, FMT seems to be a safe and effective strategy for the management of GVHD based on the current evidence. Due to the small number of patients evaluated and the absence of randomized data, one cannot portray FMT as a standard of care yet; however, the low toxicity along with the clinical improvement justifies this modality to be tested in a randomized fashion.}, }
@article {pmid35530507, year = {2022}, author = {Lai, Z and Chen, Z and Zhang, A and Niu, Z and Cheng, M and Huo, C and Xu, J}, title = {The Gut Microbiota in Liver Transplantation Recipients During the Perioperative Period.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {854017}, pmid = {35530507}, issn = {1664-042X}, abstract = {Background: Chronic liver disease is a global problem, and an increasing number of patients receive a liver transplant yearly. The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients during the perioperative. Methods: We studied gut fecal microbial community signatures in 37 Chinese adults using 16S rRNA sequencing targeting V3-V4 hypervariable regions, with a total of 69 fecal samples. We analyzed the Alpha and Beta diversities of various groups. Then we compared the abundance of bacteria in groups at the phylum, family, and genus levels. Results: The healthy gut microbiota predominantly consisted of the phyla Firmicutes and Bacteroidestes, followed by Proteobacteria and Actinobacteria. Compared with healthy people, due to the dominant bacteria in patients with chronic liver disease losing their advantages in the gut, the antagonistic effect on the inferior bacteria was reduced. The inferior bacteria multiplied in large numbers during this process. Some of these significant changes were observed in bacterial species belonging to Enterococcus, Klebsiella, and Enterobacter, which increased in patients' intestines. There were low abundances of signature genes such as Bacteroides, Prevotella, and Ruminococcus. Blautia and Bifidobacterium (considered probiotics) almost disappeared after liver transplantation. Conclusion: There is an altered microbial composition in liver transplantation patients and a distinct signature of microbiota associated with the perioperative period.}, }
@article {pmid35528013, year = {2022}, author = {Liang, F and Lu, X and Deng, Z and Zhong, HJ and Zhang, W and Li, Q and Zhou, HH and Liou, YL and He, XX}, title = {Effect of Washed Microbiota Transplantation on Patients With Dyslipidemia in South China.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {827107}, pmid = {35528013}, issn = {1664-2392}, mesh = {China/epidemiology ; Cholesterol, LDL/blood ; *Dyslipidemias/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Hyperlipidemias/therapy ; *Lipid Metabolism Disorders/therapy ; Lipids/blood ; Triglycerides/blood ; }, abstract = {BACKGROUND AND AIMS: Although the manual crude fecal microbiota transplantation (FMT) reduces blood lipids in animal models of hyperlipidemia, its clinical effect on blood lipid metabolism in patients with hyperlipidemia and hypolipidemia remains unclear, especially in the Chinese population. It was reported that washed microbiota transplantation (WMT) was safer, more precise, and more quality-controllable than the crude FMT by manual. This study aimed to investigate the feasibility and effectiveness of WMT on lipid metabolism in the Chinese population.<br><br>METHODS: Clinical data of patients with various indications who received WMT for 1-3 treatment procedures were collected. Changes in blood lipids before and after WMT, namely, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), liver fat attenuation, and liver stiffness measurement, were compared.<br><br>RESULTS: A total of 177 patients (40 cases of hyperlipidemia, 87 cases with normal blood lipids, and 50 cases of hypolipidemia) were enrolled in the First Affiliated Hospital of Guangdong Pharmaceutical University. WMT has a significant therapeutic effect in reducing blood lipid levels (TC and TG) in the short- and medium term in patients with hyperlipidemia (p <0.05). Hyper blood lipid decreased to normal in the short-term (35.14%; p <0.001), and LDL-C changed to normal in the medium term (33.33%; p = 0.013). In the hypolipidemia group, 36.36% and 47.06% changed to normal in the short-term (p = 0.006) and medium term (p = 0.005) of therapeutic effects based on blood lipid levels. In the normal blood lipid group and the low-risk group of atherosclerotic cardiovascular disease (ASCVD), the change was not statistically significant, indicating that WMT does not increase the risk of blood lipid and ASCVD in the long-term.<br><br>CONCLUSIONS: WMT treatment changes blood lipids in patients with hyperlipidemia and hypolipidemia without serious adverse events, with no risk for increasing blood lipids and ASCVD in the long-term. There were significant decreased TC, TG, and LDL-C levels in the medium term of WMT treatment for hyperlipidemia. Therefore, the regulation of gut microbiota by WMT may indicate a new clinical method for the treatment of dyslipidemia.}, }
@article {pmid35526726, year = {2022}, author = {Kinoshita, Y and Niwa, H and Uchida-Fujii, E and Nukada, T and Ueno, T}, title = {Simultaneous Daily Fecal Microbiota Transplantation Fails to Prevent Metronidazole-Induced Dysbiosis of Equine Gut Microbiota.}, journal = {Journal of equine veterinary science}, volume = {114}, number = {}, pages = {104004}, doi = {10.1016/j.jevs.2022.104004}, pmid = {35526726}, issn = {0737-0806}, mesh = {Animals ; *Dysbiosis/chemically induced/veterinary ; Fecal Microbiota Transplantation/methods/veterinary ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Horse Diseases/chemically induced ; Horses ; Metronidazole ; }, abstract = {Antimicrobial administration can lead to imbalances of gastrointestinal microbiota, called dysbiosis. Dysbiosis sometimes results in diarrhea and enteritis in horses. Fecal microbiota transplantation (FMT) is used to treat affected horses, but whether it is effective as a prophylactic approach for dysbiosis in horses receiving antimicrobials remains unknown. The aim of this study was to assess the efficacy of simultaneous FMT against metronidazole-induced dysbiosis in horses. Changes in the ratios of bacterial families, determined by metagenomic analysis, were similar between the metronidazole-treated group and the simultaneous metronidazole- and FMT-treated group, notably in the Clostridiaceae, Ruminococcaceae, and Enterobacteriaceae. Differences in fecal bacterial compositions were due mainly to metronidazole administration (P = .0003), but not to FMT (P = .3136). Simultaneous FMT at 500 g of donor feces in 1 L of suspension once a day did not inhibit metronidazole-induced dysbiosis. The results show that the FMT protocol needs to be improved to prevent metronidazole-induced gut dysbiosis in horses.}, }
@article {pmid35525320, year = {2022}, author = {Ianiro, G}, title = {An Artificial Microbiome Consortium Prevents Recurrence of Clostridioidesdifficile Infection: Paving the Way for Fecal Microbiota Transplantation 2.0.}, journal = {Gastroenterology}, volume = {163}, number = {1}, pages = {333}, doi = {10.1053/j.gastro.2022.05.002}, pmid = {35525320}, issn = {1528-0012}, mesh = {*Clostridium Infections/prevention &amp; control ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; }, }
@article {pmid35517805, year = {2022}, author = {Liu, D and Zhao, R and Wu, Y and Wang, Y and Yang, R and Ke, X}, title = {Variation in the Efficacy of Anti-Ulcerative Colitis Treatments Reveals the Conflict Between Precipitating Compatibility of Traditional Chinese Medicine and Modern Technology: A Case of Scutellaria-Coptis.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {819851}, pmid = {35517805}, issn = {1663-9812}, abstract = {Scutellariae and Coptidis compose a classical drug pair applied in clinical practice to dispel heat, dryness, and dampness, and they are also precipitation compatible drug pairs. With modern technology, Scutellaria-Coptis is mostly prepared by decocting its components separately, while in the traditional method, it is predominantly prepared as a combined decoction. The present study investigated the effects and mechanisms of separate and combined application of Scutellaria-Coptis decoction on ulcerative colitis (UC) in mice induced by the administration of dextran sulfate sodium (DSS). Changes in body weight, colon length, and Disease Activity Index scores were also evaluated. Hematoxylin and eosin staining and other methods were used to evaluate the overall condition of animals in each group. Intestinal microflora was analyzed using 16S rRNA sequencing, while colon inflammation and antioxidant capacity were evaluated based on the levels of interleukin-6 (IL-6), IL-10, IL-1β, tumor necrosis factor-α, superoxide dismutase, malondialdehyde, and reduced glutathione. The results revealed that Scutellaria-Coptis significantly relieved colon inflammation in mice, and the combined decoction of Scutellaria-Coptis exerted a significant effect on UC. Notably, the protective effect of Scutellaria-Coptis against colon inflammation was weakened when the antibiotic mixture was partially consumed by the gut microbiota. The results of 16S rRNA sequencing showed that the group treated with combined decoction of Scutellaria-Coptis exhibited a higher intestinal microbial diversity and intestinal flora composition than the separated decoction group. Treatment of mice with UC by administering Scutellaria-Coptis decoction through intestinal flora removal (ABX) and fecal microbial transplantation (FMT) was closely associated with intestinal flora composition. In conclusion, Scutellaria-Coptis can relieve UC with an excellent effect especially when taken as a combined decoction, alleviating colon inflammation incurred by intestinal microbes to a certain extent.}, }
@article {pmid35510325, year = {2022}, author = {Cheng, F and Huang, Z and Li, Z and Wei, W}, title = {Efficacy and safety of fecal microbiota transplant for recurrent Clostridium difficile infection in inflammatory bowel disease: a systematic review and meta-analysis.}, journal = {Revista espanola de enfermedades digestivas}, volume = {114}, number = {9}, pages = {543-549}, doi = {10.17235/reed.2022.8814/2022}, pmid = {35510325}, issn = {1130-0108}, mesh = {Chronic Disease ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; *Inflammatory Bowel Diseases/etiology/therapy ; Recurrence ; Treatment Outcome ; }, abstract = {OBJECTIVES: the objective of this systematic review and meta-analysis was to evaluate the outcomes of fecal microbiota transplantation (FMT) therapy for recurrent Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD) patients.<br><br>METHODS: electronic databases were searched for studies reporting on the efficacy and/or safety of FMT therapy for recurrent CDI in IBD. The meta-prop command of the meta package in R was used to assess efficacy and safety. Subgroup analyses were performed to explore heterogeneity regarding all outcomes.<br><br>RESULTS: eleven trials were included in the study. A pooled analysis showed that the initial cure rate of recurrent CDI among IBD patients was 80 % (95 % CI, 0.76, 0.84), and the overall cure rate after two or more FMT procedures was 90 % (95 % CI, 0.84, 0.94). The recurrence rate post-FMT therapy was 25 % (95 % CI: 0.20, 0.32). Sub-analyses suggested that the initial cure rate of CDI in ulcerative colitis (UC) patients was higher than in Crohn's disease (CD) patients (85 % vs. 79 %), with no statistically significant differences (p > 0.05). No serious adverse events were noted in any of the patients post-FMT.<br><br>CONCLUSIONS: FMT is an effective and safe treatment for recurrent CDI in patients with IBD. FMT should be considered early in cases of recurrent or refractory CDI. Multiple FMT procedures can improve the cure rate of CDI.}, }
@article {pmid35506416, year = {2022}, author = {Borkent, J and Ioannou, M and Laman, JD and Haarman, BCM and Sommer, IEC}, title = {Role of the gut microbiome in three major psychiatric disorders.}, journal = {Psychological medicine}, volume = {52}, number = {7}, pages = {1222-1242}, pmid = {35506416}, issn = {1469-8978}, mesh = {*Bipolar Disorder/therapy ; *Depressive Disorder, Major/therapy ; *Gastrointestinal Microbiome ; Humans ; *Mental Disorders/therapy ; *Probiotics/therapeutic use ; }, abstract = {Major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia-spectrum disorders (SSD) are heterogeneous psychiatric disorders, which place significant burden on patient's well-being and global health. Disruptions in the gut-microbiome may play a role in these psychiatric disorders. This review presents current data on composition of the human gastrointestinal microbiota, and its interaction mechanisms in the gut-brain axis in MDD, BD and SSD. Diversity metrics and microbial relative abundance differed across studies. More studies reported inconsistent findings (n = 7) or no differences (n = 8) than studies who reported lower α-diversity in these psychiatric disorders (n = 5). The most consistent findings across studies were higher relative abundances of the genera Streptococcus, Lactobacillus, and Eggerthella and lower relative abundance of the butyrate producing Faecalibacterium in patients with psychiatric disorders. All three increased genera were associated with higher symptom severity. Confounders, such as medication use and life style have not been accounted for. So far, the results of probiotics trials have been inconsistent. Most traditional and widely used probiotics (consisting of Bifidobacterium spp. and Lactobacillus spp.) are safe, however, they do not correct potential microbiota disbalances in these disorders. Findings on prebiotics and faecal microbiota transplantation (FMT) are too limited to draw definitive conclusions. Disease-specific pro/prebiotic treatment or even FMT could be auspicious interventions for prevention and therapy for psychiatric disorders and should be investigated in future trials.}, }
@article {pmid35506256, year = {2022}, author = {Wang, C and Wei, S and Liu, B and Wang, F and Lu, Z and Jin, M and Wang, Y}, title = {Maternal consumption of a fermented diet protects offspring against intestinal inflammation by regulating the gut microbiota.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2057779}, pmid = {35506256}, issn = {1949-0984}, mesh = {Animals ; Diet ; Female ; *Gastrointestinal Microbiome/physiology ; Humans ; Inflammation ; Lactobacillus ; Maternal Nutritional Physiological Phenomena ; Mice ; *Probiotics/pharmacology ; Swine ; }, abstract = {The neonatal intestinal tract is immature and can be easily infected by pathogens causing inflammation. Maternal diet manipulation is a promising nutritional strategy to enhance the gut health of offspring. A fermented diet is a gut microbiota targeting diet containing live probiotics and their metabolites, which benefit the gut and overall health host. However, it remains unclear how a maternal fermented diet (MFD) affects neonatal intestinal inflammation. Here, in vivo and in vitro models together with multi-omics analysis were applied to investigate the impacts and the underlying mechanism through which an MFD prevents from gut inflammation in neonates. An MFD remarkably improved the performance of both sows and piglets and significantly altered the gut microbiome and milk metabolome of sows. In addition, the MFD significantly accelerated the maturation of the gut microbiota of neonates and increased the abundance of gut Lactobacillus and the microbial functions of amino acid-related enzymes and glucose metabolism on the weaning day. Notably, the MFD reduced susceptibility to colonic inflammation in offspring. The fecal microbiota of sows was then transplanted into mouse dams and it was found that the mouse dams and pups in the MFD group alleviated the LPS-induced decrease in gut Lactobacillus abundance and barrier injury. Milk L-glutamine (GLN) and gut Lactobacillus reuteri (LR) were found as two of the main MFD-induced sow effectors that contributed to the gut health of piglets. The properties of LR and GLN in modulating gut microbiota and alleviating colonic inflammation by inhibiting the phosphorylation of p38 and JNK and activation of Caspase 3 were further verified. These findings provide the first data revealing that an MFD drives neonate gut microbiota development and ameliorates the colonic inflammation by regulating the gut microbiota. This fundamental evidence might provide references for modulating maternal nutrition to enhance early-life gut health and prevent gut inflammation.}, }
@article {pmid35506083, year = {2022}, author = {Oliveira, AC and Yang, T and Li, J and Sharma, RK and Karas, MK and Bryant, AJ and de Kloet, AD and Krause, EG and Joe, B and Richards, EM and Raizada, MK}, title = {Fecal matter transplant from Ace2 overexpressing mice counteracts chronic hypoxia-induced pulmonary hypertension.}, journal = {Pulmonary circulation}, volume = {12}, number = {1}, pages = {e12015}, pmid = {35506083}, issn = {2045-8932}, support = {R01 HL102033/HL/NHLBI NIH HHS/United States ; R01 HL110170/HL/NHLBI NIH HHS/United States ; R01 HL143082/HL/NHLBI NIH HHS/United States ; }, abstract = {Recent evidence suggests pulmonary hypertension (PH), a disease of the pulmonary vasculature actually has multiorgan pathophysiology and perhaps etiology. Herein, we demonstrated that fecal matter transplantation from angiotensin-converting enzyme 2 overexpressing mice counteracted the effects of chronic hypoxia to prevent pulmonary hypertension, neuroinflammation, and gut dysbiosis in wild type recipients.}, }
@article {pmid35501923, year = {2022}, author = {Parker, A and Romano, S and Ansorge, R and Aboelnour, A and Le Gall, G and Savva, GM and Pontifex, MG and Telatin, A and Baker, D and Jones, E and Vauzour, D and Rudder, S and Blackshaw, LA and Jeffery, G and Carding, SR}, title = {Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {68}, pmid = {35501923}, issn = {2049-2618}, support = {BB/CCG1860/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N000250/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10355/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Aging ; Animals ; Brain ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Inflammation/pathology ; Mice ; }, abstract = {BACKGROUND: Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina.<br><br>METHODS: Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing.<br><br>RESULTS: We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota.<br><br>CONCLUSIONS: These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut-brain and gut-retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life. Video abstract.}, }
@article {pmid35500802, year = {2022}, author = {Li, X and Zhao, W and Xiao, M and Yu, L and Chen, Q and Hu, X and Zhao, Y and Xiong, L and Chen, X and Wang, X and Ba, Y and Guo, Q and Wu, X}, title = {Penthorum chinense Pursh. extract attenuates non-alcholic fatty liver disease by regulating gut microbiota and bile acid metabolism in mice.}, journal = {Journal of ethnopharmacology}, volume = {294}, number = {}, pages = {115333}, doi = {10.1016/j.jep.2022.115333}, pmid = {35500802}, issn = {1872-7573}, mesh = {Animals ; Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; Plant Extracts/therapeutic use ; RNA, Ribosomal, 16S/genetics ; Taurine/metabolism ; }, abstract = {Penthorum chinense Pursh. (PCP) is commonly used as a Miao ethnomedicine and health food for liver protection in China. Gansukeli (WS3-B-2526-97) is made from the extract of PCP (PCPE) for the treatment of viral hepatitis. In recent years, PCPE has been reported in the treatment of non-alcoholic fatty liver disease (NAFLD), however its potential mechanism is not fully elucidated.<br><br>AIM OF THE STUDY: To investigate the ameliorating effect of PCPE on high-fat diet (HFD)-induced NAFLD mice and demonstrate whether its protective effect is gut microbiota dependent and associated with bile acid (BA) metabolism.<br><br>MATERIALS AND METHODS: The alleviating effect of PCPE on NAFLD was conducted on male C57BL/6J mice fed an HFD for 16 weeks, and this effect associated with gut microbiota dependent was demonstrated by pseudo-germfree mice treated with antibiotics and fecal microbiota transplantation (FMT). The composition of the gut microbiota in the cecum contents was analyzed by 16S rRNA sequencing, and the levels of BAs in liver and fecal samples were determined by UPLC/MS-MS.<br><br>RESULTS: The results showed that administration of PCPE for 8 weeks could potently ameliorate HFD-induced NAFLD and alleviate dyslipidemia and insulin resistance. Moreover, PCPE treatment alleviated gut dysbiosis, especially reducing the relative abundance of bile salt hydrolase (BSH)-producing bacteria. Furthermore, PCPE significantly increased the levels of taurine-conjugated BAs in feces, such as tauro-&#x3b2;-muricholic acid (T-&#x3b2;MCA), tauroursodesoxycholic acid (TUDCA), and taurochenodeoxycholic acid (TCDCA), and increased hepatic chenodeoxycholic acid (CDCA). The protein and mRNA expression of farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) were decreased in intestine, increased taurine-conjugated BAs inhibited the intestinal signaling pathway, which was associated with increased genes expression of enzymes in the alternative BA synthesis pathway that reduced the levels of cholesterol. The increased CDCA produced via the alternative BA synthesis pathway promoted hepatic FXR activation and BA excretion.<br><br>CONCLUSION: Our study is the first time to demonstrate that PCPE could ameliorate NAFLD in HFD-induced mice by regulating the gut microbiota and BA metabolism, and from a novel perspective, to clarify the mechanism of PCPE in NAFLD.}, }
@article {pmid35499059, year = {2022}, author = {Shen, Q and Huang, Z and Yao, J and Jin, Y}, title = {Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease.}, journal = {Journal of advanced research}, volume = {37}, number = {}, pages = {221-233}, pmid = {35499059}, issn = {2090-1224}, mesh = {Dysbiosis ; *Extracellular Vesicles/pathology ; Humans ; *Inflammatory Bowel Diseases/pathology/therapy ; Intestines/pathology ; *Microbiota ; }, abstract = {BACKGROUND: The intestinal tract is a complicated ecosystem with dynamic homeostasis via interaction of intestine and microbiota. Inflammatory bowel disease (IBD) is chronic intestinal inflammation involving dysbiosis of intestinal microenvironment. Extracellular vesicles (EVs), as vital characteristics of cell-cell and cell-organism communication, contribute to homeostasis in intestine. Recently, EVs showed excellent potential for clinical applications in disease diagnoses and therapies.<br><br>AIM OF REVIEW: Our current review discusses the modulatory functions of EVs derived from different sources in intestine, especially their effects and applications in IBD clinical therapy. EV-mediated interaction systems between host intestine and microbiota were established to describe possible mechanisms of IBD pathogenesis and its cure.<br><br>EVs are excellent vehicles for delivering molecules containing genetic information to recipient cells. Multiple pieces of evidence have illustrated that EVs participate the interaction between host and microbiota in intestinal microenvironment. In inflammatory intestine with dysbiosis of microbiota, EVs as regulators target promoting immune response and microbial reconstruction. EVs-based immunotherapy could be a promising therapeutic approach for the treatment of IBD in the near future.}, }
@article {pmid35499044, year = {2022}, author = {Wu, C and Zhao, Y and Zhang, Y and Yang, Y and Su, W and Yang, Y and Sun, L and Zhang, F and Yu, J and Wang, Y and Guo, P and Zhu, B and Wu, S}, title = {Gut microbiota specifically mediates the anti-hypercholesterolemic effect of berberine (BBR) and facilitates to predict BBR's cholesterol-decreasing efficacy in patients.}, journal = {Journal of advanced research}, volume = {37}, number = {}, pages = {197-208}, pmid = {35499044}, issn = {2090-1224}, mesh = {Animals ; Bacteria ; *Berberine/pharmacology/therapeutic use ; Cholesterol/pharmacology ; *Gastrointestinal Microbiome ; Humans ; *Hyperlipidemias/drug therapy ; Mice ; }, abstract = {INTRODUCTION: Gut microbiota has been implicated in the pharmacological activities of many natural products. As an effective hypolipidemic agent, berberine (BBR)'s clinical application is greatly impeded by the obvious inter-individual response variation. To date, little evidence exists on the causality between gut microbes and its therapeutic effects, and the linkage of bacteria alterations to the inter-individual response variation.<br><br>OBJECTIVES: This study aims to confirm the causal role of the gut microbiota in BBR's anti-hyperlipidemic effect and identify key bacteria that can predict its effectiveness.<br><br>METHODS: The correlation between gut microbiota and BBR's inter-individual response variation was studied in hyperlipidemic patients. The causal role of gut microbes in BBR's anti-hyperlipidemic effects was subsequently assessed by altered administration routes, co-treatment with antibiotics, fecal microbiota transplantation, and metagenomic analysis.<br><br>RESULTS: Three-month clinical study showed that BBR was effectively to decrease serum lipids but displayed an obvious response variation. The cholesterol-lowering but not triglyceride-decreasing effect of BBR was closely related to its modulation on gut microbiota. Interestingly, the baseline levels of Alistipes and Blautia could accurately predict its anti-hypercholesterolemic efficiency in the following treatment. Causality experiments in mice further confirmed that the gut microbiome is both necessary and sufficient to mediate the lipid-lowering effect of BBR. The absence of Blautia substantially abolished BBR's cholesterol-decreasing efficacy.<br><br>CONCLUSION: The gut microbiota is necessary and sufficient for BBR's hyperlipidemia-ameliorating effect. The baseline composition of gut microbes can be an effective predictor for its pharmacotherapeutic efficacy, providing a novel way to achieve personalized therapy.}, }
@article {pmid35498721, year = {2022}, author = {Liu, T and Guo, Y and Lu, C and Cai, C and Gao, P and Cao, G and Li, B and Guo, X and Yang, Y}, title = {Effect of Different Pig Fecal Microbiota Transplantation on Mice Intestinal Function and Microbiota Changes During Cold Exposure.}, journal = {Frontiers in veterinary science}, volume = {9}, number = {}, pages = {805815}, pmid = {35498721}, issn = {2297-1769}, abstract = {Cold stress influences intestinal processes, causing physiological and immunological responses in animals. Intestinal microbiota participates in maintaining the stability of the intestinal environment. However, phenotypic characteristics and the effects of porcine microbiota changes under cold conditions remain poorly understood. Here, the fecal microbiota of cold tolerant breed (Mashen) and cold sensitive breed (Duroc-Landrace-Yorkshire) was transferred to germ-free mice, respectively. After a cold exposure (4°C) for 21 days, intestinal function and microbe changes of mice were explored. The results showed that Mashen pigs microbiota transplantation made the body temperature of the mice stable, in which the fat weight and expression of uncoupling protein 1 (UCP1), carnitine palmitoyltransferase 1B (Cpt1b), and Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) were significantly higher (P < 0.05) than those of the control group. The results of intestinal structure and expression of serum inflammatory factors showed that fecal microbiota transplantation (FMT) mice have more intact intestinal structure and high expression of proinflammatory factor such as interleukin-4 (IL-4). The study of mice fecal microbiome characterized via 16S rRNA sequencing found that pig microbiota transplantation changed the abundance of Firmicutes. In addition, it identified discriminative features of Firmicutes in the microbiota between two breeds of pig, in which Clostridiaceae were enriched in the microbiota community of Mashen pig and Coriobacteriales were significantly (P < 0.05) enriched in the Duroc-Landrace-Yorkshire pig microbiota transplantation group based on linear discriminant analysis effect size (LEfSe) analysis. Finally, we found that the content of propionic acid and butyric acid in rectal contents significantly changed and the abundances of Clostridium and Lachnospira showed significant correlations with changes in short-chain fatty acids. The results suggest that pig fecal microbiota transplantation can alleviate the changes in physiological and biochemical indicators in mice caused by cold exposure. Mice have gut microbes altered and improved gut barrier function via fecal microbiota transplantation in pigs.}, }
@article {pmid35496818, year = {2021}, author = {Wang, Q and Wang, X and Lv, Y and Yang, C and Zhou, C and Wang, L}, title = {Changes in Rats' Gut Microbiota Composition Caused by Induced Chronic Myocardial Infarction Lead to Depression-Like Behavior.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {641084}, pmid = {35496818}, issn = {1664-302X}, abstract = {Depression is common among patients who have chronic myocardial infarction (CMI). Despite their frequency, depression and CMI are bidirectional related conditions, each is a risk for the other, and they often co-exist, suggesting shared or interacting pathomechanisms. Accumulating data revealed the effects of gut microbiota in terms of regulating depression via the gut-brain axis. Thus, we investigated the role of gut microbial dysbiosis in CMI-induced depression-like behavior. Hierarchical cluster analysis of sucrose preference test (SPT) results was adopted to classify the CMI rats into depression-like behavior (CMI + Dep) or non-depression-like behavior (CMI + Non-Dep) phenotypes. First, 16S ribosomal RNA sequencing analysis showed both β-diversity and relative abundance of several gut bacteria significantly differed between the CMI + Dep and CMI + Non-Dep rats. Next, transplantation of fecal microbiota from CMI + Dep rats visibly altered the relative abundance of gut microbiota and also induced depression-like behavior in the antibiotics-treated pseudo-germ-free rats. In conclusion, these findings suggested that dysbiosis in gut microbial composition contributed to the onset of CMI-induced depression-like behavior and that exogenous regulation of gut microbiota composition could be a potential therapeutic strategy for CMI and related depression-like behavior.}, }
@article {pmid35495114, year = {2022}, author = {Xu, P and Lv, T and Dong, S and Cui, Z and Luo, X and Jia, B and Jeon, CO and Zhang, J}, title = {Association between intestinal microbiome and inflammatory bowel disease: Insights from bibliometric analysis.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {1716-1725}, pmid = {35495114}, issn = {2001-0370}, abstract = {The gut microbiome is highly linked to inflammatory bowel disease (IBD). A total of 3890 publications related to the two terms from 2000 to 2020 were extracted from the Web of Science Core Collection to study the association from a bibliometric perspective. Publications on this topic have grown rapidly since 2008. The United States and Harvard University are the country and institution with the largest number of publications, respectively. Inflammatory Bowel Diseases is the most productive journal with 211 published articles. The most influential journal in this field is Gut with 13,359 citations. The co-citation analysis of references showed that the IBD-related topics with the highest focus are "gut microbiota," "metagenomics," "bacterial community," "fecal microbiota transplantation," "probiotics," and "colitis-associated colorectal cancer." Keyword cluster and keyword burst analyses showed that "gut microbiota," "metagenomics," and "fecal microbiota transplantation" are currently the most researched topics in the field of IBD. The literature in this field is mainly distributed between alterations of the intestinal microbiota, microbial metabolites, and related host signaling pathways. Probiotic treatment also frequently appears in literature. This bibliometric analysis can guide future research and promote the development of the field of gut microbiome and IBD.}, }
@article {pmid35493741, year = {2022}, author = {Xing, J and Liao, Y and Zhang, H and Zhang, W and Zhang, Z and Zhang, J and Wang, D and Tang, D}, title = {Impacts of MicroRNAs Induced by the Gut Microbiome on Regulating the Development of Colorectal Cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {804689}, pmid = {35493741}, issn = {2235-2988}, mesh = {*Colorectal Neoplasms/microbiology ; Faecalibacterium prausnitzii ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; *MicroRNAs/genetics ; }, abstract = {Although a dysfunctional gut microbiome is strongly linked to colorectal cancer (CRC), our knowledge of the mediators between CRC and the microbiome is limited. MicroRNAs (miRNAs) affect critical cellular processes, such as apoptosis, proliferation, and differentiation, and contribute to the regulation of CRC progression. Increasingly, studies found that miRNAs can significantly mediate bidirectional interactions between the host and the microbiome. Notably, miRNA expression is regulated by the gut microbiome, which subsequently affects the host transcriptome, thereby influencing the development of CRC. This study typically focuses on the specific functions of the microbiome in CRC and their effect on CRC-related miRNA production and reviews the role of several bacteria on miRNA, including Fusobacterium nucleatum, Escherichia coli, enterotoxigenic Bacteroides fragilis, and Faecalibacterium prausnitzii. Based on the important roles of miRNAs and the gut microbiome in CRC, strategies for modulating miRNA expression and regulating the gut microbiome composition need to be applied, such as bioactive dietary components and fecal microorganism transplantation.}, }
@article {pmid35490629, year = {2022}, author = {Lamberte, LE and van Schaik, W}, title = {Antibiotic resistance in the commensal human gut microbiota.}, journal = {Current opinion in microbiology}, volume = {68}, number = {}, pages = {102150}, doi = {10.1016/j.mib.2022.102150}, pmid = {35490629}, issn = {1879-0364}, support = {BB/S017941/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Drug Resistance, Bacterial/genetics ; *Gastrointestinal Microbiome/genetics ; Gene Transfer, Horizontal ; Humans ; Symbiosis ; }, abstract = {Antibiotic-resistant infections are a major threat to global public health and there is an urgent need to develop new drugs and interventions to treat and prevent infections caused by antibiotic-resistant bacteria. The human gut microbiota harbours both commensals and opportunistic pathogens which can acquire resistance to antibiotics through mutation and horizontal gene transfer. The powerful combination of modern high-throughput DNA sequencing and microbiological culture methods is providing novel insights into the mechanisms of antibiotic resistance among, up to recently poorly studied, commensal bacteria in the gut. Interventions to minimise the abundance of antibiotic-resistant commensals and opportunistic pathogens include faecal microbiota transplantation and the use of live biotherapeutics, but the efficacy of these treatments remains elusive.}, }
@article {pmid35489181, year = {2022}, author = {Ezquer, F and Quintanilla, ME and Morales, P and Santapau, D and Munita, JM and Moya-Flores, F and Ezquer, M and Herrera-Marschitz, M and Israel, Y}, title = {A dual treatment blocks alcohol binge-drinking relapse: Microbiota as a new player.}, journal = {Drug and alcohol dependence}, volume = {236}, number = {}, pages = {109466}, doi = {10.1016/j.drugalcdep.2022.109466}, pmid = {35489181}, issn = {1879-0046}, mesh = {Acetylcysteine/pharmacology/therapeutic use ; Alcohol Drinking ; *Alcohol-Related Disorders ; *Alcoholism/drug therapy ; Animals ; Aspirin ; Chronic Disease ; Ethanol ; Humans ; Mice ; *Microbiota ; Rats ; Recurrence ; }, abstract = {RATIONALE: Gut microbiota communicates information to the brain. Some animals are born with a gut microbiota that predisposes to high alcohol consumption, and transplantation of fecal material from alcoholics to mice increases animal preference for ethanol. Alcohol-use-disorders are chronic conditions where relapse is the hallmark. A predictive animal model of relapse is the "alcohol deprivation effect" where ethanol re-access is allowed following chronic alcohol intake and a long alcohol deprivation. The present study evaluates the effect of gut microbiota modification on relapse, as an adjunct to N-acetylcysteine + Acetylsalicylic acid administration, which inhibits the alcohol-induced hyper-glutamatergic condition.<br><br>METHODS: Rats bred as heavy alcohol consumers (UChB) were allowed ethanol intake for one month, were deprived of alcohol for two-weeks and subsequently offered re-access to ethanol. Prior to ethanol re-access animals received orally either (i) vehicle-control, (ii) Lactobacillus-rhamnosus-GG after antibiotic treatment (LGG); (iii) N-acetylcysteine+Acetylsalicylic acid (NAC/ASA) or (iv) both treatments: LGG+&#xa0;(NAC/ASA).<br><br>RESULTS: Marked binge drinking (1.75&#xa0;g ethanol/kg in 60&#xa0;min) and blood alcohol levels exceeding 80&#xa0;mg/dl were observed in the control group upon ethanol-re-access. Lactobacillus-GG or (NAC+ASA) treatments inhibited alcohol intake by 66-80%. The combination of both treatments virtually suppressed (inhibition of 90%) the re-access binge-like drinking, showing additive effects. Treatment with NAC+ASA increased the levels of glutamate transporters xCT and GLT-1 in nucleus accumbens, while Lactobacillus-GG administration increased those of the dopamine transporter (DAT).<br><br>CONCLUSIONS: The administration of a well-accepted probiotic may be of value as an adjunct in the treatment of alcohol-use-disorders.}, }
@article {pmid35488243, year = {2022}, author = {Lu, Y and Yuan, X and Wang, M and He, Z and Li, H and Wang, J and Li, Q}, title = {Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies.}, journal = {Journal of hematology &amp; oncology}, volume = {15}, number = {1}, pages = {47}, pmid = {35488243}, issn = {1756-8722}, support = {81973715//the General program of National Natural Science Foundation of China/ ; ZYYCXTD-C-202001//the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine/ ; 81301912//National Natural Science Foundation of China/ ; BHTPP202008//the Beijing Municipal Health and Scientific and Technological Achievements and Appropriate Technology Promotion Project/ ; YYZSCQ202003//the "High-value Patent Cultivation" project of the Beijing Friendship Hospital Affiliated to the Capital Medical University/ ; YYQDKT2019-40//the Research Foundation of Beijing Friendship Hospital/ ; 82174243//General program of National Natural Science Foundation of China/ ; }, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunity ; Immunotherapy ; *Microbiota ; }, abstract = {The gut microbiota have long been recognized to play a key role in human health and disease. Currently, several lines of evidence from preclinical to clinical research have gradually established that the gut microbiota can modulate antitumor immunity and affect the efficacy of cancer immunotherapies, especially immune checkpoint inhibitors (ICIs). Deciphering the underlying mechanisms reveals that the gut microbiota reprogram the immunity of the tumor microenvironment (TME) by engaging innate and/or adaptive immune cells. Notably, one of the primary modes by which the gut microbiota modulate antitumor immunity is by means of metabolites, which are small molecules that could spread from their initial location of the gut and impact local and systemic antitumor immune response to promote ICI efficiency. Mechanistic exploration provides novel insights for developing rational microbiota-based therapeutic strategies by manipulating gut microbiota, such as fecal microbiota transplantation (FMT), probiotics, engineered microbiomes, and specific microbial metabolites, to augment the efficacy of ICI and advance the age utilization of microbiota precision medicine.}, }
@article {pmid35487886, year = {2022}, author = {Wang, B and Zhang, L and Wang, Y and Dai, T and Qin, Z and Zhou, F and Zhang, L}, title = {Alterations in microbiota of patients with COVID-19: potential mechanisms and therapeutic interventions.}, journal = {Signal transduction and targeted therapy}, volume = {7}, number = {1}, pages = {143}, pmid = {35487886}, issn = {2059-3635}, mesh = {*COVID-19/complications/therapy ; Cell Line ; Humans ; *Microbiota ; Peptidyl-Dipeptidase A/metabolism ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The global coronavirus disease 2019 (COVID-19) pandemic is currently ongoing. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high proportion of COVID-19 patients exhibit gastrointestinal manifestations such as diarrhea, nausea, or vomiting. Moreover, the respiratory and gastrointestinal tracts are the primary habitats of human microbiota and targets for SARS-CoV-2 infection as they express angiotensin-converting enzyme-2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) at high levels. There is accumulating evidence that the microbiota are significantly altered in patients with COVID-19 and post-acute COVID-19 syndrome (PACS). Microbiota are powerful immunomodulatory factors in various human diseases, such as diabetes, obesity, cancers, ulcerative colitis, Crohn's disease, and certain viral infections. In the present review, we explore the associations between host microbiota and COVID-19 in terms of their clinical relevance. Microbiota-derived metabolites or components are the main mediators of microbiota-host interactions that influence host immunity. Hence, we discuss the potential mechanisms by which microbiota-derived metabolites or components modulate the host immune responses to SARS-CoV-2 infection. Finally, we review and discuss a variety of possible microbiota-based prophylaxes and therapies for COVID-19 and PACS, including fecal microbiota transplantation (FMT), probiotics, prebiotics, microbiota-derived metabolites, and engineered symbiotic bacteria. This treatment strategy could modulate host microbiota and mitigate virus-induced inflammation.}, }
@article {pmid35486073, year = {2022}, author = {El-Salhy, M and Mazzawi, T and Hausken, T and Hatlebakk, JG}, title = {The fecal microbiota transplantation response differs between patients with severe and moderate irritable bowel symptoms.}, journal = {Scandinavian journal of gastroenterology}, volume = {57}, number = {9}, pages = {1036-1045}, doi = {10.1080/00365521.2022.2064725}, pmid = {35486073}, issn = {1502-7708}, mesh = {Fatigue ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/diagnosis ; Quality of Life ; RNA, Ribosomal, 16S ; Treatment Outcome ; }, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is a promising intervention for patients with irritable bowel syndrome (IBS). The present study aimed to identify any differences in FMT response between patients with severe and moderate IBS symptoms.<br><br>MATERIALS AND METHOD: The study included the 164 patients who participated in our previous study, of which 96 (58.5%) and 68 (41.5%) had severe (S-IBS-S) and moderate (Mo-IBS-S) IBS, respectively. The patients were randomly divided into a placebo group (own feces) and 30-g and 60-g (donor feces) FMT groups. Patients completed three questionnaires that assessed their symptoms and quality of life at baseline and at 2&#x2009;weeks, 1&#x2009;month, and 3&#x2009;months after FMT, and provided fecal samples before and 1&#x2009;month after FMT. The fecal bacteria were analyzed using the 16S rRNA gene in PCR DNA amplification covering the V3-V9 variable genes.<br><br>RESULTS: Response rates of the placebo group did not differ between S-IBS-S and Mo-IBS-S patients at 2&#x2009;weeks, 1&#x2009;month and 3&#x2009;months after FMT. The response rates in the active treatment group were higher in S-IBS-S patients than in Mo-IBS-S patients at each observation time. FMT reduced abdominal symptoms and fatigue and improved the quality of life in patients with both severe and moderate IBS. Patients with S-IBS-S had higher levels of Eubacterium siraeum, and lower levels of Eubacterium rectale than Mo-IBS-S, after FMT.<br><br>CONCLUSION: Patients with S-IBS-S have a higher response rate to FMT and a marked improvement in fatigue and in quality of life compared with those with Mo-IBS-S. The clinical trial registration number is NCT03822299 and is available at www.clinicaltrials.gov.}, }
@article {pmid35481834, year = {2022}, author = {Zou, YT and Zhou, J and Zhu, JH and Wu, CY and Shen, H and Zhang, W and Zhou, SS and Xu, JD and Mao, Q and Zhang, YQ and Long, F and Li, SL}, title = {Gut Microbiota Mediates the Protective Effects of Traditional Chinese Medicine Formula Qiong-Yu-Gao against Cisplatin-Induced Acute Kidney Injury.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0075922}, pmid = {35481834}, issn = {2165-0497}, mesh = {*Acute Kidney Injury/chemically induced/metabolism/prevention &amp; control ; Animals ; Cisplatin/adverse effects ; *Drugs, Chinese Herbal/pharmacology ; Fibrosis ; *Gastrointestinal Microbiome ; Histone Deacetylases/metabolism ; Inflammation ; Medicine, Chinese Traditional ; Mice ; }, abstract = {Our previous study found that Qiong-Yu-Gao (QYG), a traditional Chinese medicine formula derived from Rehmanniae Radix, Poria, and Ginseng Radix, has protective effects against cisplatin-induced acute kidney injury (AKI), but the underlying mechanisms remain unknown. In the present study, the potential role of gut microbiota in the nephroprotective effects of QYG was investigated. We found that QYG treatment significantly attenuated cisplatin-induced AKI and gut dysbiosis, altered the levels of bacterial metabolites, with short-chain fatty acids (SCFAs) such as acetic acid and butyric acid increasing and uremic toxins such as indoxyl sulfate and p-cresyl sulfate reducing, and suppressed histone deacetylase expression and activity. Spearman's correlation analysis found that QYG-enriched fecal bacterial genera Akkermansia, Faecalibaculum, Bifidobacterium, and Lachnospiraceae_NK4A136_group were correlated with the altered metabolites, and these metabolites were also correlated with the biomarkers of AKI, as well as the indicators of fibrosis and inflammation. The essential role of gut microbiota was further verified by both the diminished protective effects with antibiotics-induced gut microbiota depletion and the transferable renal protection with fecal microbiota transplantation. All these results suggested that gut microbiota mediates the nephroprotective effects of QYG against cisplatin-induced AKI, potentially via increasing the production of SCFAs, thus suppressing histone deacetylase expression and activity, and reducing the accumulation of uremic toxins, thereby alleviating fibrosis, inflammation, and apoptosis in renal tissue. IMPORTANCE Cisplatin-induced acute kidney injury is the main limiting factor restricting cisplatin's clinical application. Accumulating evidence indicated the important role of gut microbiota in pathogenesis of acute kidney injury. In the present study, we have demonstrated that gut microbiota mediates the protective effects of traditional Chinese medicine formula Qiong-Yu-Gao against cisplatin-induced acute kidney injury. The outputs of this study would provide scientific basis for future clinical applications of QYG as prebiotics to treat cisplatin-induced acute kidney injury, and gut microbiota may be a promising therapeutic target for chemotherapy-induced nephrotoxicity.}, }
@article {pmid35481347, year = {2022}, author = {Hu, B and Das, P and Lv, X and Shi, M and Aa, J and Wang, K and Duan, L and Gilbert, JA and Nie, Y and Wu, XL}, title = {Effects of 'Healthy' Fecal Microbiota Transplantation against the Deterioration of Depression in Fawn-Hooded Rats.}, journal = {mSystems}, volume = {7}, number = {3}, pages = {e0021822}, pmid = {35481347}, issn = {2379-5077}, mesh = {Rats ; Animals ; *Fecal Microbiota Transplantation ; Rats, Sprague-Dawley ; *Depression/therapy ; Dysbiosis/therapy ; Feces ; Cytokines ; }, abstract = {Depression is a recurrent, heterogeneous mood disorder occurring in more than 260 million people worldwide. Gut microbiome dysbiosis is associated with the development of depressive-like behaviors by modulating neuro-biochemical metabolism through the microbiome-gut-brain (MGB) axis. Fecal microbiota transplantation (FMT) has been proposed as a potential therapeutic solution for depression, but the therapeutic efficiency and mechanism are unknown. Here, we performed an FMT from Sprague-Dawley (SD) rats ('healthy' controls) to Fawn-hooded (FH) rats (depression model). Pre-FMT, the FH rats exhibited significantly elevated depressive-like behaviors and distinct neurotransmitter and cytokine levels compared with SD rats. Post-FMT, FH recipients receiving FH fecal microbiota (FH-FH rats) showed aggravated depressive-like behaviors, while the ones receiving SD microbiota (FH-SD rats) had significantly alleviated depressive symptoms, a significant increase in hippocampal neurotransmitters, and a significant decrease of some hippocampal cytokines than FH-FH rats. SD-FMT resulted in the FH-SD rats' gut microbiome resembling the SD donors, and a significant shift in the serum metabolome but not the hippocampal metabolome. Co-occurrence analysis suggests that SD-FMT prevented recipients' depression development via the significant decrease of gut microbial species such as Dialister sp., which led to the recipients' metabolic modulation in serum and hippocampus through the enteric nervous system, the intestinal barrier, and the blood-brain barrier. Our results provided new data pointing to multiple mechanisms of interaction for the impact of gut microbiome modulation on depression therapy. IMPORTANCE Depression is a chronic, recurrent mental disease, which could make the patients commit suicide in severe cases. Considering that gut microbiome dysbiosis could cause depressive symptoms in animals through the MGB axis, the modification of gut microbiota is expected to be a potential therapy for depression, but the daily administration of probiotics is invalid or transient. In this study, we demonstrated that the gut microbiome transferred from a healthy rat model to a depressive rat model could regulate the recipient's neurobiology and behavior via the systematic alternation of the depressive gut microbiota followed by the serum and hippocampal metabolism. These results underline the significance of understanding the impact of gut microbiota on mental disorders and suggest that 'healthy' microbiota transplantation with the function to solve the host's cerebral inflammation may serve as a novel therapeutic strategy for depression.}, }
@article {pmid35479587, year = {2022}, author = {Rapoport, EA and Baig, M and Puli, SR}, title = {Adverse events in fecal microbiota transplantation: a systematic review and meta-analysis.}, journal = {Annals of gastroenterology}, volume = {35}, number = {2}, pages = {150-163}, pmid = {35479587}, issn = {1108-7471}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a highly efficacious procedure used most commonly for the treatment of recurrent Clostridioides difficile infection (CDI). Despite the high value of incorporating FMT into practice, there remain concerns about its safety. To the best of our knowledge, there has not been an updated meta-analysis reporting pooled rates of adverse events in FMT for CDI.<br><br>METHODS: A search for studies of FMT in patients with CDI was performed with the rate of serious adverse events (SAEs) related to FMT evaluated as the primary outcome. Secondary outcomes included SAEs unrelated to FMT and minor adverse events associated with FMT. A pooled analysis was then performed.<br><br>RESULTS: Initial search identified 378 reference articles. Data were extracted from the 61 of these studies that met the inclusion criteria, comprising 5099 patients. Pooled analysis showed that SAEs related to FMT developed in less than 1% of patients. The pooled rate of SAEs not related to FMT was higher at 2.9%. The pooled rate of minor adverse events also showed infrequent self-limited gastrointestinal and systemic discomfort.<br><br>CONCLUSIONS: This meta-analysis supports FMT as a safe option for treating recurrent CDI. Future randomized trials are needed to improve our current understanding of FMT safety and further examine the improvements in the quality of life of patients treated with FMT compared to standard therapy of antibiotics.}, }
@article {pmid35475976, year = {2022}, author = {Li, S and Zhao, X and Lin, F and Ni, X and Liu, X and Kong, C and Yao, X and Mo, Y and Dai, Q and Wang, J}, title = {Gut Flora Mediates the Rapid Tolerance of Electroacupuncture on Ischemic Stroke by Activating Melatonin Receptor through Regulating Indole-3-Propionic Acid.}, journal = {The American journal of Chinese medicine}, volume = {50}, number = {4}, pages = {979-1006}, doi = {10.1142/S0192415X22500409}, pmid = {35475976}, issn = {1793-6853}, mesh = {Animals ; *Brain Ischemia/metabolism/therapy ; *Electroacupuncture ; *Gastrointestinal Microbiome ; *Indoles/metabolism ; Infarction, Middle Cerebral Artery ; *Ischemic Stroke/therapy ; Mice ; *Receptors, Melatonin/metabolism ; }, abstract = {Electroacupuncture (EA) is commonly used to treat cerebrovascular diseases. This study aimed to clarify the mechanisms of action of treatments of cerebral ischemic stroke from the perspective of gut microecology. We used a mouse model and cell cultures to investigate the effects of EA on the intestinal microflora in mice models of middle cerebral artery occlusion (MCAO) and the mechanisms underlying the antioxidant activities of metabolites. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota. Metabolomic analysis was performed to characterize the metabolic profile differences between the mice in the EA + MCAO and MCAO groups. Gavaging with feces relieved brain damage in mice that received EA (EA mice) more than in mice that did not (non-EA [NEA] mice). The gut microbial composition and metabolic profiles of the EA and NEA mice were different. In particular, the microbiota from the mice in the EA or EA-FMT groups generated more indole-3-propionic acid (IPA) than the microbiota from the mice in the MCAO or NEA-FMT groups. We confirmed that IPA binds to specific melatonin receptors (MTRs) in target cells and exerts antioxidant effects by adding MTR inhibitors or knocking out the MTR1 gene in vivo and in the oxygen and glucose deprivation/reperfusion models of N2a cell experiments. EA can prevent ischemic stroke by improving the composition of intestinal microbiota in MCAO mice. Moreover, this study reveals a new mechanism of intestinal flora regulation of stroke that differs from inflammation/immunity, namely gut microbiota regulates stroke by affecting IPA levels.}, }
@article {pmid35474500, year = {2022}, author = {Kumar, P and Brazel, D and DeRogatis, J and Valerin, JBG and Whiteson, K and Chow, WA and Tinoco, R and Moyers, JT}, title = {The cure from within? a review of the microbiome and diet in melanoma.}, journal = {Cancer metastasis reviews}, volume = {41}, number = {2}, pages = {261-280}, pmid = {35474500}, issn = {1573-7233}, support = {R01 AI137239/AI/NIAID NIH HHS/United States ; T32 CA009054/CA/NCI NIH HHS/United States ; R01 AI137230/AI/NIAID NIH HHS/United States ; }, mesh = {Diet ; Humans ; Immunotherapy ; *Melanoma/therapy ; *Microbiota ; *Skin Neoplasms/therapy ; }, abstract = {Therapy for cutaneous melanoma, the deadliest of the skin cancers, is inextricably linked to the immune system. Once thought impossible, cures for metastatic melanoma with immune checkpoint inhibitors have been developed within the last decade and now occur regularly in the clinic. Unfortunately, half of tumors do not respond to checkpoint inhibitors and efforts to further exploit the immune system are needed. Tantalizing associations with immune health and gut microbiome composition suggest we can improve the success rate of immunotherapy. The gut contains over half of the immune cells in our bodies and increasingly, evidence is linking the immune system within our gut to melanoma development and treatment. In this review, we discuss the importance the skin and gut microbiome may play in the development of melanoma. We examine the differences in the microbial populations which inhabit the gut of those who develop melanoma and subsequently respond to immunotherapeutics. We discuss the role of dietary intake on the development and treatment of melanoma. And finally, we review the landscape of published and registered clinical trials therapeutically targeting the microbiome in melanoma through dietary supplements, fecal microbiota transplant, and microbial supplementation.}, }
@article {pmid35472435, year = {2022}, author = {Zhu, L and Ye, C and Hu, B and Xia, H and Bian, Q and Liu, Y and Kong, M and Zhou, S and Liu, H}, title = {Regulation of gut microbiota and intestinal metabolites by Poria cocos oligosaccharides improves glycolipid metabolism disturbance in high-fat diet-fed mice.}, journal = {The Journal of nutritional biochemistry}, volume = {107}, number = {}, pages = {109019}, doi = {10.1016/j.jnutbio.2022.109019}, pmid = {35472435}, issn = {1873-4847}, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Glycolipids/pharmacology ; *Insulins/pharmacology ; *Metabolic Diseases ; Mice ; Mice, Inbred C57BL ; Oligosaccharides/chemistry/pharmacology ; *Wolfiporia ; }, abstract = {In this study, we aimed to explore the effect of Poria cocos oligosaccharides (PCO) on glucolipid metabolism disorder. Based on a high-fat diet (HFD)-induced obese mouse model, we demonstrated that PCO ameliorated glucose intolerance and insulin resistance, decreased the levels of blood glucose (187.8±19.8 mg/dL) and insulin (566.3±53.34 ng/L) in HFD-fed mice compared to the Ctrl group (140.4±7.942 mg/dL for glucose, 423.2±19.56 ng/L for insulin). Moreover, PCO treatment suppressed the mRNA expressions of fatty acid synthesis regulators (decreases of 68.8%, 62.8%, and 32.0% for G6Pase, FASN, and DGAT, respectively, vs. HFD group) and pro-inflammatory cytokines in epididymal fat (decreases of 71.9%, 81.5%, 76.0%, 29.3%, and 63.9% for TNF-α, IL-1β, IL-6, COX-5b, and MCP-1, respectively, vs. HFD group). Also, PCO treatment alleviated damage to the intestinal barrier of HFD-fed mice. By 16S rDNA gene sequencing, PCO partly restored the imbalance of gut microbiota in HFD-fed mice, accompanied by the reversal of several intestinal metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), and tryptophan metabolites. By Spearman's correlation analysis, we found that the changed gut microbiota and their metabolites were significantly correlated with the alteration of metabolic markers. Finally, the significance of gut microbiota in PCO-mediated improvement on glucolipid metabolism disorder was confirmed by an antibiotic depletion experiment and fecal microbiota transplantation. In summary, PCO may be used as a novel prebiotic in the treatment of glucolipid disorders by reshaping intestinal bacteria structure. Our studies also point towards the potential of Poria cocos as a healthy food in the clinical application to metabolic diseases in the future.}, }
@article {pmid35469400, year = {2022}, author = {Mesa López, MJ and Salazar Nicolás, A and Leal Rubio, JD and Muñoz Tornero, M and Egea Valenzuela, J}, title = {Extramedullary plasmacytoma with colonic involvement: experience in a tertiary hospital.}, journal = {Revista espanola de enfermedades digestivas}, volume = {114}, number = {10}, pages = {629-630}, doi = {10.17235/reed.2022.8828/2022}, pmid = {35469400}, issn = {1130-0108}, mesh = {Adult ; Aged ; Bortezomib/therapeutic use ; Dexamethasone/therapeutic use ; *Diabetes Mellitus, Type 2/drug therapy ; Female ; Humans ; Immunoglobulin G ; Male ; Melphalan/therapeutic use ; *Multiple Myeloma/complications/therapy ; *Plasmacytoma/therapy ; Prednisone/therapeutic use ; Rituximab ; Tertiary Care Centers ; }, abstract = {A 71-year-old woman diagnosed with type II diabetes mellitus with severe iron deficiency anemia and positive fecal occult blood. Colonoscopy was performed, showing a soft mass in the ascending colon, with biopsies compatible with plasmacytoma and restriction for Kappa light chains. After bone marrow aspiration, associated IgG multiple myeloma was detected, so chemotherapy with VMP (bortezomib, melphalan and prednisone) was started. Colonoscopy six months later showed that the ulcerated lesion had a reduction in tumor size of up to 80%. A 27-year-old male with a history of kidney transplantation and symptoms of chronic diarrhea, colonoscopy was indicated with the finding of a large exophytic and ulcerated lesion in the cecum. Pathology revealed plasmacytoma with restriction of lambda light chains. After ruling out lesions in other locations, the patient was treated with immunochemotherapy according to the Bortezomib-Rituximab-Dexamethasone scheme, with subsequent complete clinical and endoscopic remission. Plasmacytoma accounts for < 4 % of plasma cell tumours. It may appear isolated or associated with another plasma cell neoplasm, mainly multiple myeloma. Its presence in the gastrointestinal tract is rare, being infrequent in the stomach or small intestine, and even rarer in the colonic tract (incidence 1/10,000,000). The clinical manifestations are similar to those of other colon neoplasms, while the treatment or prognosis may differ from those of other neoplasms. In patients with clinical suspicion, it is important to perform an early endoscopic study, especially in patients diagnosed with multiple myeloma.}, }
@article {pmid35468731, year = {2022}, author = {Hao, Y and Feng, Y and Yan, X and Chen, L and Zhong, R and Tang, X and Shen, W and Sun, Q and Sun, Z and Ren, Y and Zhang, H and Zhao, Y}, title = {Gut microbiota-testis axis: FMT improves systemic and testicular micro-environment to increase semen quality in type 1 diabetes.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {28}, number = {1}, pages = {45}, pmid = {35468731}, issn = {1528-3658}, mesh = {Animals ; *Diabetes Mellitus, Type 1/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Semen Analysis ; Streptozocin ; Testis ; }, abstract = {BACKGROUND: Clinical data suggest that male reproductive dysfunction especially infertility is a critical issue for type 1 diabetic patient (T1D) because most of them are at the reproductive age. Gut dysbiosis is involved in T1D related male infertility. However, the improved gut microbiota can be used to boost spermatogenesis and male fertility in T1D remains incompletely understood.<br><br>METHODS: T1D was established in ICR (CD1) mice with streptozotocin. Alginate oligosaccharide (AOS) improved gut microbiota (fecal microbiota transplantation (FMT) from AOS improved gut microbiota; A10-FMT) was transplanted into the T1D mice by oral administration. Semen quality, gut microbiota, blood metabolism, liver, and spleen tissues were determined to investigate the beneficial effects of A10-FMT on spermatogenesis and underlying mechanisms.<br><br>RESULTS: We found that A10-FMT significantly decreased blood glucose and glycogen, and increased semen quality in streptozotocin-induced T1D subjects. A10-FMT improved T1D-disturbed gut microbiota, especially the increase in small intestinal lactobacillus, and blood and testicular metabolome to produce n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to ameliorate spermatogenesis and semen quality. Moreover, A10-FMT can improve spleen and liver functions to strengthen the systemic environment for sperm development. FMT from gut microbiota of control animals (Con-FMT) produced some beneficial effects; however, to a smaller extent.<br><br>CONCLUSIONS: AOS-improved gut microbiota (specific microbes) may serve as a novel, promising therapeutic approach for the improvement of semen quality and male fertility in T1D patients via gut microbiota-testis axis.}, }
@article {pmid35468018, year = {2022}, author = {Caruso, S and Marrone, G and Gentile, G}, title = {Case 305.}, journal = {Radiology}, volume = {303}, number = {2}, pages = {477-479}, doi = {10.1148/radiol.210452}, pmid = {35468018}, issn = {1527-1315}, mesh = {Echocardiography ; Electrocardiography ; *Heart Ventricles/diagnostic imaging ; Humans ; Male ; Stroke Volume ; *Ventricular Function, Left ; }, abstract = {A 27-year-old man was admitted to the emergency department with fever and thoracic pain. In the previous 6 months, the patient lost a substantial amount of weight (12 kg). His family history was negative for cardiac disease. Electrocardiography revealed sinus rhythm, and diffuse T-wave inversion. Two-dimensional echocardiography was performed (Fig 1) and revealed normal left systolic function (ejection fraction, 60%). Laboratory tests showed elevated levels of high-sensitivity cardiac troponin (1.07 ng/mL; normal value, <0.015 ng/mL), high levels of C-reactive protein (16 mg/dL; normal range, 0-5 mg/dL), and leukocytosis with an eosinophilia level of 8710/μL (normal level, <400/μL). Parasitic and infectious diseases (Toxocara canis, strongyloides, filariasis, cysticercosis, fasciola, trichinella, echinococcosis) were excluded based on blood and fecal test results. Corticosteroid therapy was started, and the patient was dismissed. A few days later, he was readmitted to the emergency department with a headache and suddenly blurred vision. Neurologic and ophthalmologic findings were normal, and MRI of the brain was performed (Fig 2). Cardiac MRI (Fig 3) was performed 2 days later and revealed the following quantitative results: (a) left ventricular end-diastolic volume (LVDV) of 165 mL (LVDV/body surface area [BSA], 89 mL/m[2]; normal range, 64-100 mL/m[2]), left ventricular end-systolic volume (LVSV) of 80 mL (LVSV/BSA, 43 mL/m[2]; normal range, 17-39 mL/m[2]); stroke volume (SV) of 85 mL (SV/BSA, 46 mL/m[2]; normal range, 43-67 mL/m[2]); and ejection fraction of 52% and (b) right ventricular end-diastolic volume (RVDV) of 163 mL (RVDV/BSA, 88 mL/m[2]; normal range, 63-111 mL/m[2]), right ventricular end-systolic volume (RVSV) of 81 mL (RVSV/BSA, 44 mL/m[2]; normal range, 32-92 mL/m[2]); stroke volume (SV) of 82 mL (SV/BSA, 44 mL/m[2]; normal range, 39-71 mL/m[2]); and ejection fraction of 50%.}, }
@article {pmid35467645, year = {2022}, author = {Xiao, Y and Zhong, XS and Liu, X and Li, Q}, title = {Therapeutic Evaluation of Fecal Microbiota Transplantation in an Interleukin 10-deficient Mouse Model.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {182}, pages = {}, pmid = {35467645}, issn = {1940-087X}, support = {R01 HL152683/HL/NHLBI NIH HHS/United States ; R21 AI126097/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Colitis ; Disease Models, Animal ; Fecal Microbiota Transplantation/methods ; Humans ; *Inflammatory Bowel Diseases/therapy ; Interleukin-10/genetics ; Mice ; Mice, Inbred C57BL ; }, abstract = {With the development of microecology in recent years, the relationship between intestinal bacteria and inflammatory bowel disease (IBD) has attracted considerable attention. Accumulating evidence suggests that dysbiotic microbiota plays an active role in triggering or worsening the inflammatory process in IBD and that fecal microbiota transplantation (FMT) is an attractive therapeutic strategy since transferring a healthy microbiota to IBD patient could restore the appropriate host-microbiota communication. However, the molecular mechanisms are unclear, and the efficacy of FMT has not been very well established. Thus, further studies in animal models of IBD are necessary. In this method, we applied FMT from wild-type C57BL/6J mice to IL-10 deficient mice, a widely used mouse model of colitis. The study elaborates on collecting fecal pellets from the donor mice, making the fecal solution/suspension, administering the fecal solution, and monitoring the disease. We found that FMT significantly mitigated the cardiac impairment in IL-10 knockout mice, underlining its therapeutic potential for IBD management.}, }
@article {pmid35467388, year = {2022}, author = {Jing, Y and Bai, F and Wang, L and Yang, D and Yan, Y and Wang, Q and Zhu, Y and Yu, Y and Chen, Z}, title = {Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0017722}, pmid = {35467388}, issn = {2165-0497}, mesh = {Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Inflammation/pathology ; Mice ; Nerve Growth Factors ; *Neuroprotective Agents/pharmacology ; Rats ; Rats, Sprague-Dawley ; *Spinal Cord Injuries/metabolism/pathology/therapy ; beta-Alanine ; }, abstract = {The primary traumatic event that causes spinal cord injury (SCI) is followed by a progressive secondary injury featured by vascular disruption and ischemia, inflammatory responses and the release of cytotoxic debris, which collectively add to the hostile microenvironment of the lesioned cord and inhibit tissue regeneration and functional recovery. In a previous study, we reported that fecal microbiota transplantation (FMT) promotes functional recovery in a contusion SCI mouse model; yet whether and how FMT treatment may impact the microenvironment at the injury site are not well known. In the current study, we examined individual niche components and investigated the effects of FMT on microcirculation, inflammation and trophic factor secretion in the spinal cord of SCI mice. FMT treatment significantly improved spinal cord tissue sparing, vascular perfusion and pericyte coverage and blood-spinal cord-barrier (BSCB) integrity, suppressed the activation of microglia and astrocytes, and enhanced the secretion of neurotrophic factors. Suppression of inflammation and upregulation of trophic factors, jointly, may rebalance the niche homeostasis at the injury site and render it favorable for reparative and regenerative processes, eventually leading to functional recovery. Furthermore, microbiota metabolic profiling revealed that amino acids including β-alanine constituted a major part of the differentially detected metabolites between the groups. Supplementation of β-alanine in SCI mice reduced BSCB permeability and increased the number of surviving neurons, suggesting that β-alanine may be one of the mediators of FMT that participates in the modulation and rebalancing of the microenvironment at the injured spinal cord. IMPORTANCE FMT treatment shows a profound impact on the microenvironment that involves microcirculation, blood-spinal cord-barrier, activation of immune cells, and secretion of neurotrophic factors. Analysis of metabolic profiles reveals around 22 differentially detected metabolites between the groups, and β-alanine was further chosen for functional validation experiments. Supplementation of SCI mice with β-alanine significantly improves neuronal survival, and the integrity of blood-spinal cord-barrier at the lesion site, suggesting that β-alanine might be one of the mediators following FMT that has contributed to the recovery.}, }
@article {pmid35465162, year = {2022}, author = {Feng, T and Liu, Y}, title = {Microorganisms in the reproductive system and probiotic's regulatory effects on reproductive health.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {1541-1553}, pmid = {35465162}, issn = {2001-0370}, abstract = {The presence of microbial communities in the reproductive tract has been revealed, and this resident microbiota is involved in the maintenance of health. Intentional modulation via probiotics has been proposed as a possible strategy to enhance reproductive health and reduce the risk of diseases. The male seminal microbiota has been suggested as an important factor that influences a couple's health, pregnancy outcomes, and offspring health. Probiotics have been reported to play a role in male fertility and to affect the health of mothers and offspring. While the female reproductive microbiota is more complicated and has been identified in both the upper and lower reproductive systems, they together contribute to health maintenance. Probiotics have shown regulatory effects on the female reproductive tract, thereby contributing to homeostasis of the tract and influencing the health of offspring. Further, through transmission of bacteria or through other indirect mechanisms, the parent's reproductive microbiota and probiotic intervention influence infant gut colonization and immunity development, with potential health consequences. In vitro and in vivo studies have explored the mechanisms underlying the benefits of probiotic administration and intervention, and an array of positive results, such as modulation of microbiota composition, regulation of metabolism, promotion of the epithelial barrier, and improvement of immune function, have been observed. Herein, we review the state of the art in reproductive system microbiota and its role in health and reproduction, as well as the beneficial effects of probiotics on reproductive health and their contributions to the prevention of associated diseases.}, }
@article {pmid35463939, year = {2022}, author = {Hammeken, LH and Baunwall, SMD and Dahlerup, JF and Hvas, CL and Ehlers, LH}, title = {Health-related quality of life in patients with recurrent Clostridioides difficile infections.}, journal = {Therapeutic advances in gastroenterology}, volume = {15}, number = {}, pages = {17562848221078441}, pmid = {35463939}, issn = {1756-283X}, abstract = {BACKGROUND: The health-related quality of life (HrQoL) can be substantially affected in patients with recurrent Clostridioides difficile infection (rCDI) but the impact of effective treatment of the infection remains unclear. This study aimed to evaluate the HrQoL in patients with rCDI and estimate the gain in HrQoL associated with effective treatment of rCDI.<br><br>METHODS: Patients' HrQoL was estimated based on EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaires obtained from a Danish randomised controlled trial (RCT). In the RCT, 64 patients with rCDI were randomised to receive either vancomycin (n&#x2009;=&#x2009;16), fidaxomicin (n&#x2009;=&#x2009;24) or faecal microbiota transplantation (FMT) preceded by vancomycin (n&#x2009;=&#x2009;24). The primary outcome in the RCT was rCDI resolution. Patients were closely monitored during the RCT, and rescue FMT was offered to those who failed their primary treatment. Patients' HrQoL was measured at baseline and at 8- and 26-weeks follow-up. Linear regression analyses conditional on the differences between baseline and follow-up measurements were used to assess statistical significance (p&#x2009;<&#x2009;0.05).<br><br>RESULTS: Within 26&#x2009;weeks of follow-up, 13 (81%) patients treated with vancomycin, 12 (50%) patients treated with fidaxomicin, and 3 (13%) patients treated with FMT had a subsequent recurrence and received a rescue FMT. The average HrQoL for untreated patients with rCDI was 0.675. After receiving effective treatment, this value increased by 0.139 to 0.813 (p&#x2009;<&#x2009;0.001) at week 8 and by 0.098 to 0.773 (p&#x2009;=&#x2009;0.003) at week 26 of follow-up compared with baseline.<br><br>CONCLUSION: The HrQoL was adversely affected in patients with an active episode of rCDI but increased substantially after receiving an effective treatment algorithm in which rescue FMT was provided in case of a primary treatment failure.<br><br>TRIAL REGISTRATION: The RCT was preregistered at EudraCT (j.no. 2015-003004-24, https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003004-24/results) and at ClinicalTrials.gov (study identifier NCT02743234, https://clinicaltrials.gov/ct2/show/NCT02743234).}, }
@article {pmid35462505, year = {2022}, author = {Zhou, Y and Li, YY and Liu, Y}, title = {[Effect of fecal microbiota transplantation on type 1 diabetes mellitus in non-obese diabetic mice and its underlying mechanism].}, journal = {Zhonghua yi xue za zhi}, volume = {102}, number = {16}, pages = {1224-1231}, doi = {10.3760/cma.j.cn112137-20210907-02043}, pmid = {35462505}, issn = {0376-2491}, support = {82070849, 81770778, 81800735//National Natural Science Foundation of China/ ; 20182015//Innovation and Entrepreneurship Team Project in Jiangsu Province/ ; }, mesh = {Amino Acids ; Animals ; *Diabetes Mellitus, Experimental ; *Diabetes Mellitus, Type 1/therapy ; Fecal Microbiota Transplantation ; Female ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; RNA, Ribosomal, 16S ; }, abstract = {Objective: To investigate the effects of fecal microbiota transplantation (FMT) on non-obese diabetic (NOD) mice of type 1 diabetes mellitus (T1DM) and its underlying mechanisms. Methods: A total of 8-9 week-female NOD mice were randomly divided into control (n=36) and FMT groups (n=36) according to the random number table. Fecal microbiota from C57BL/6 mice were transplanted into FMT group, and control group were transplanted with microbiota from themselves, once every two days for 5 times. The insulitis score and incidence of T1DM were compared between two groups;16S rRNA gene sequencing was used to evaluate the structure of fecal bacteria in NOD mice. The expressions of intestinal barrier related genes were detected by real-time quantitative PCR. The proportions of regulatory T cells (Tregs), helper T cell (Th)-1 and Th17 in the enteric-pancreatic immune axis were detected by flow cytometry. Amino acid in serum was measured by amino acid metabolomics. Results: Incidence of T1DM in NOD mice from FMT group was 40.9% (9/22), lower than 72.7% (13/22) from control group at 26 weeks of age (P=0.034). FMT promoted colonization of probiotics such as Lactobacillus, Clostridium_sp_ND2, Candidatus_Arthromitus and Clostridiaceae_1; mRNA of intestinal barrier related genes were up-regulated in FMT group [ mucins(Muc)-1: 0.93±0.29 vs 2.97±0.79, P=0.036; Muc2: 0.72±0.39 vs 10.70±3.54, P=0.019;Muc3: 1.79±0.69 vs 10.97±2.78, P=0.009;Muc4: 1.01±0.23 vs 2.42±0.49, P=0.029;Occludin(Ocln): 0.96±0.08 vs 1.81±0.36, P=0.045; Claudin(Cldn)-1:0.94±0.17 vs 2.20±0.43, P=0.022] compared to control. The proportions of Treg in mesenteric lymphoid node, pancreatic lymph node and peyer's patches of FMT group [(6.10±0.49)% vs (7.54±0.27)%, P=0.020;(5.28±0.39)% vs (6.42±0.34)%, P=0.048;(6.78±0.42)% vs (7.88±0.13)%, P=0.029] were increased compared to control,while proportions of Th1 [(1.02±0.06)% vs (0.83±0.06)%, P=0.040;(0.82±0.10)% vs (0.56±0.05)%, P=0.038;(1.28±0.12) vs (0.85±0.07), P=0.012] and proportions of Th17 [(0.40±0.01)% vs (0.30±0.02)%, P=0.004;(0.40±0.02)% vs (0.31±0.02)%, P=0.008;(0.51±0.06) vs (0.36±0.02), P=0.027] were decreased. The contents of leucine [(92.86±7.32) vs (91.87±12.62) μmol/L, P=0.027], valine [(162.74±15.97) vs (155.89±25.70) μmol/L, P=0.046] and isoleucine [(75.65±5.59) vs (73.61±9.67) μmol/L, P=0.048] in serum were decreased in FMT group. Conclusions: FMT can alleviate insulitis and T1DM occurrence in NOD mice, of which mechanism may be related to remodeling gut microbiota and improving intestinal barrier function, affecting immune response of enteric-pancreatic immune axis, correcting amino acid metabolism disorder and reducing the accumulation of branch chain amino acids in NOD mice.}, }
@article {pmid35461908, year = {2022}, author = {Macareño-Castro, J and Solano-Salazar, A and Dong, LT and Mohiuddin, M and Espinoza, JL}, title = {Fecal microbiota transplantation for Carbapenem-Resistant Enterobacteriaceae: A systematic review.}, journal = {The Journal of infection}, volume = {84}, number = {6}, pages = {749-759}, doi = {10.1016/j.jinf.2022.04.028}, pmid = {35461908}, issn = {1532-2742}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; *Carbapenem-Resistant Enterobacteriaceae ; Carrier State ; *Enterobacteriaceae Infections/therapy ; Escherichia coli ; Fecal Microbiota Transplantation/adverse effects ; Humans ; Prospective Studies ; Randomized Controlled Trials as Topic ; Retrospective Studies ; }, abstract = {The prevalence of Carbapenem-resistant Enterobacteriaceae (CRE) has increased dramatically in recent years and has become a global public health issue. Since carbapenems are considered the last drugs of choice, infections caused by these pathogens are difficult to treat and carry a high risk of mortality. Several antibiotic combination regimens have been utilized for the management of CRE infections or to eradicate colonization in CRE carriers with variable clinical responses. In addition, recent studies have explored the use of fecal microbiota transplantation (FMT) to eradicate CRE infections. Here, we conducted a systematic review of publications in which FMT was used to eliminate CRE colonization in infected individuals. We searched the PubMed, Cochrane, and Medline databases up to November 30, 2021. Ten studies (209 patients) met the inclusion criteria for this review with three articles describing retrospective cohorts (n = 53 patients) and seven reporting prospective data (n = 156 patients), including one randomized open-label clinical trial. All studies were published between 2017 and 2021 with eight studies from Europe and two from South Korea. There were substantial variations in terms of outcome measurements and study endpoint among these studies. Among the 112 FMT recipients with confirmed CRE colonization, CRE decolonization was reported in 55/90 cases at one month after FMT and at the end of the study follow-up (6-12 months), decolonization was documented in 74/94 (78.7%) patients. The predominant CRE strains reported were Klebsiella pneumoniae and Escherichia coli and the most frequently documented carbapenemases were KPC, OXA-48, and NDM. In general, FMT was well tolerated, with no severe complications reported even in immunosuppressed patients and in those with multiple underlying conditions. In conclusion, FMT appears to be safe and effective in eradicating CRE colonization, however, more studies, especially randomized trials, are needed to validate the safety and clinical utility of FMT for CRE eradication.}, }
@article {pmid35461735, year = {2022}, author = {Husain, U and Sharma, A and Khurana, S and Bhushan, B and Datta, P}, title = {Cyclosporiasis in an immunocompromised patient who had undergone renal allograft transplant-A rare case report.}, journal = {Indian journal of medical microbiology}, volume = {40}, number = {3}, pages = {465-467}, doi = {10.1016/j.ijmmb.2022.03.004}, pmid = {35461735}, issn = {1998-3646}, mesh = {Allografts ; *COVID-19 ; *Cyclospora ; *Cyclosporiasis/complications/diagnosis/drug therapy ; Diarrhea/diagnosis/etiology ; Feces ; *Foodborne Diseases ; Humans ; Immunocompromised Host ; *Kidney Transplantation/adverse effects ; Male ; Middle Aged ; SARS-CoV-2 ; Travel ; }, abstract = {Cyclospora spp. is an important cause of traveler's diarrhea or water and food-borne diarrhoeal diseases. We present an interesting but rare case report of cyclosporiasis in a 51-year-old male who had undergone renal allograft transplant six years ago. He also had a past history of tuberculosis, cytomegalovirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and hepatitis C infection and was being treated with immunosuppressants. The patient had a prolonged history of gastrointestinal manifestations with recent acute onset of watery diarrhea associated with abdominal cramps. Stool examination after modified Ziehl-Neelsen staining revealed oocysts of Cyclospora spp. The patient was successfully treated with cotrimoxazole.}, }
@article {pmid35461318, year = {2022}, author = {Hou, K and Wu, ZX and Chen, XY and Wang, JQ and Zhang, D and Xiao, C and Zhu, D and Koya, JB and Wei, L and Li, J and Chen, ZS}, title = {Microbiota in health and diseases.}, journal = {Signal transduction and targeted therapy}, volume = {7}, number = {1}, pages = {135}, pmid = {35461318}, issn = {2059-3635}, mesh = {*Dysbiosis/therapy ; *Gastrointestinal Microbiome ; Homeostasis ; Humans ; Immunity ; Inflammation ; }, abstract = {The role of microbiota in health and diseases is being highlighted by numerous studies since its discovery. Depending on the localized regions, microbiota can be classified into gut, oral, respiratory, and skin microbiota. The microbial communities are in symbiosis with the host, contributing to homeostasis and regulating immune function. However, microbiota dysbiosis can lead to dysregulation of bodily functions and diseases including cardiovascular diseases (CVDs), cancers, respiratory diseases, etc. In this review, we discuss the current knowledge of how microbiota links to host health or pathogenesis. We first summarize the research of microbiota in healthy conditions, including the gut-brain axis, colonization resistance and immune modulation. Then, we highlight the pathogenesis of microbiota dysbiosis in disease development and progression, primarily associated with dysregulation of community composition, modulation of host immune response, and induction of chronic inflammation. Finally, we introduce the clinical approaches that utilize microbiota for disease treatment, such as microbiota modulation and fecal microbial transplantation.}, }
@article {pmid35458209, year = {2022}, author = {Thye, AY and Law, JW and Tan, LT and Thurairajasingam, S and Chan, KG and Letchumanan, V and Lee, LH}, title = {Exploring the Gut Microbiome in Myasthenia Gravis.}, journal = {Nutrients}, volume = {14}, number = {8}, pages = {}, pmid = {35458209}, issn = {2072-6643}, support = {FRGS/1/2019/SKK08/MUSM/02/7//Fundamental Research Grant Scheme/ ; STG-000051//Jeffrey Cheah School of Medicine and Health Sciences Strategic Grant 2021/ ; }, mesh = {Bacteria/genetics ; Biomarkers ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Myasthenia Gravis ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human gut microbiota is vital for maintaining human health in terms of immune system homeostasis. Perturbations in the composition and function of microbiota have been associated with several autoimmune disorders, including myasthenia gravis (MG), a neuromuscular condition associated with varying weakness and rapid fatigue of the skeletal muscles triggered by the host's antibodies against the acetylcholine receptor (AChR) in the postsynaptic muscle membrane at the neuromuscular junction (NMJ). It is hypothesized that perturbation of the gut microbiota is associated with the pathogenesis of MG. The gut microbiota community profiles are usually generated using 16S rRNA gene sequencing. Compared to healthy individuals, MG participants had an altered gut microbiota's relative abundance of bacterial taxa, particularly with a drop in Clostridium. The microbial diversity related to MG severity and the overall fecal short-chain fatty acids (SCFAs) were lower in MG subjects. Changes were also found in terms of serum biomarkers and fecal metabolites. A link was found between the bacterial Operational Taxonomic Unit (OTU), some metabolite biomarkers, and MG's clinical symptoms. There were also variations in microbial and metabolic markers, which, in combination, could be used as an MG diagnostic tool, and interventions via fecal microbiota transplant (FMT) could affect MG development. Probiotics may influence MG by restoring the gut microbiome imbalance, aiding the prevention of MG, and lowering the risk of gut inflammation by normalizing serum biomarkers. Hence, this review will discuss how alterations of gut microbiome composition and function relate to MG and the benefits of gut modulation.}, }
@article {pmid35458198, year = {2022}, author = {Liu, X and Hu, G and Wang, A and Long, G and Yang, Y and Wang, D and Zhong, N and Jia, J}, title = {Black Tea Reduces Diet-Induced Obesity in Mice via Modulation of Gut Microbiota and Gene Expression in Host Tissues.}, journal = {Nutrients}, volume = {14}, number = {8}, pages = {}, pmid = {35458198}, issn = {2072-6643}, mesh = {Animals ; *Camellia sinensis ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Gene Expression ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/etiology/prevention &amp; control ; Tea ; }, abstract = {Black tea was reported to alter the microbiome populations and metabolites in diet-induced obese mice and displays properties that prevent obesity, but the underlying mechanism of the preventative effect of black tea on high-fat diet (HFD) induced obesity has not been elucidated. Epigenetic studies are a useful tool for determining the relationship between obesity and environment. Here, we show that the water extract of black tea (Lapsang souchong, LS) reverses HFD-induced gut dysbiosis, alters the tissue gene expression, changes the level of a major epigenetic modification (DNA methylation), and prevents obesity in HFD feeding mice. The anti-obesity properties of black tea are due to alkaloids, which are the principal active components. Our data indicate that the anti-obesity benefits of black tea are transmitted via fecal transplantation, and the change of tissue gene expression and the preventative effects on HFD-induced obesity in mice of black tea are dependent on the gut microbiota. We further show that black tea could regulate the DNA methylation of imprinted genes in the spermatozoa of high-fat diet mice. Our results show a mechanistic link between black tea, changes in the gut microbiota, epigenetic processes, and tissue gene expression in the modulation of diet-induced metabolic dysfunction.}, }
@article {pmid35456788, year = {2022}, author = {van Thiel, IAM and Rahman, S and Hakvoort, TBM and Davids, M and Verseijden, C and van Hamersveld, PHP and Bénard, MV and Lodders, MH and Boekhout, T and van den Wijngaard, RM and Heinsbroek, SEM and Ponsioen, CY and de Jonge, WJ}, title = {Fecal Filobasidium Is Associated with Clinical Remission and Endoscopic Response following Fecal Microbiota Transplantation in Mild-to-Moderate Ulcerative Colitis.}, journal = {Microorganisms}, volume = {10}, number = {4}, pages = {}, pmid = {35456788}, issn = {2076-2607}, support = {LSHM17028//Health Holland/ ; LSHM20085//Health Holland/ ; }, abstract = {Fecal microbiota transplantation (FMT) has the potential to restore (bacterial and fungal) microbial imbalance in ulcerative colitis (UC) patients and contribute to disease remission. Here, we aimed to identify fecal fungal species associated with the induction of clinical remission and endoscopic response to FMT for patients with mild-to-moderate ulcerative colitis. We analyzed the internal transcribed spacer 1 (ITS1)-based mycobiota composition in fecal samples from patients (n = 31) and donors (n = 7) that participated previously in a double-blinded randomized control trial evaluating the efficacy of two infusions of donor FMT compared with autologous FMT. The abundance of the yeast genus Filobasidium in fecal material used for transplantation was shown to correlate with clinical remission following FMT, irrespective of its presence in the material of donor or autologous fecal microbiota transfer. The amplified sequence variants within the genus Filobasidium most closely resembled Filobasidium magnum. Monocyte-derived macrophages and HT29 epithelial cells were stimulated with fungal species. Especially Filobasidium floriforme elicited an IL10 response in monocyte-derived macrophages, along with secretion of other cytokines following stimulation with other Filobasidium species. No effect of Filobasidium spp. was seen on epithelial wound healing in scratch assays. In conclusion, the enriched presence of Filobasidium spp. in donor feces is associated with the positive response to FMT for patients with UC and hence it may serve as a predictive fungal biomarker for successful FMT.}, }
@article {pmid35456757, year = {2022}, author = {Farooq, RK and Alamoudi, W and Alhibshi, A and Rehman, S and Sharma, AR and Abdulla, FA}, title = {Varied Composition and Underlying Mechanisms of Gut Microbiome in Neuroinflammation.}, journal = {Microorganisms}, volume = {10}, number = {4}, pages = {}, pmid = {35456757}, issn = {2076-2607}, abstract = {The human gut microbiome has been implicated in a host of bodily functions and their regulation, including brain development and cognition. Neuroinflammation is a relatively newer piece of the puzzle and is implicated in the pathogenesis of many neurological disorders. The microbiome of the gut may alter the inflammatory signaling inside the brain through the secretion of short-chain fatty acids, controlling the availability of amino acid tryptophan and altering vagal activation. Studies in Korea and elsewhere highlight a strong link between microbiome dynamics and neurocognitive states, including personality. For these reasons, re-establishing microbial flora of the gut looks critical for keeping neuroinflammation from putting the whole system aflame through probiotics and allotransplantation of the fecal microbiome. However, the numerosity of the microbiome remains a challenge. For this purpose, it is suggested that wherever possible, a fecal microbial auto-transplant may prove more effective. This review summarizes the current knowledge about the role of the microbiome in neuroinflammation and the various mechanism involved in this process. As an example, we have also discussed the autism spectrum disorder and the implication of neuroinflammation and microbiome in its pathogenesis.}, }
@article {pmid35456735, year = {2022}, author = {Monteiro, RC and Rafeh, D and Gleeson, PJ}, title = {Is There a Role for Gut Microbiome Dysbiosis in IgA Nephropathy?.}, journal = {Microorganisms}, volume = {10}, number = {4}, pages = {}, pmid = {35456735}, issn = {2076-2607}, support = {11-IDEX-0005-02//Agence Nationale de la Recherche/ ; EQU201903007816//Fondation pour la Recherche Strat&#xe9;gique/ ; }, abstract = {Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and one of the leading causes of renal failure worldwide. The pathophysiology of IgAN involves nephrotoxic IgA1-immune complexes. These complexes are formed by galactose-deficient (Gd) IgA1 with autoantibodies against the hinge region of Gd-IgA1 as well as soluble CD89, an immune complex amplifier with an affinity for mesangial cells. These multiple molecular interactions result in the induction of the mesangial IgA receptor, CD71, injuring the kidney and causing disease. This review features recent immunological and microbiome studies that bring new microbiota-dependent mechanisms developing the disease based on data from IgAN patients and a humanized mouse model of IgAN. Dysbiosis of the microbiota in IgAN patients is also discussed in detail. Highlights of this review underscore that nephrotoxic IgA1 in the humanized mice originates from mucosal surfaces. Fecal microbiota transplantation (FMT) experiments in mice using stools from patients reveal a possible microbiota dysbiosis in IgAN with the capacity to induce progression of the disease whereas FMT from healthy hosts has beneficial effects in mice. The continual growth of knowledge in IgAN patients and models can lead to the development of new therapeutic strategies targeting the microbiota to treat this disease.}, }
@article {pmid35456041, year = {2022}, author = {Sonali, S and Ray, B and Ahmed Tousif, H and Rathipriya, AG and Sunanda, T and Mahalakshmi, AM and Rungratanawanich, W and Essa, MM and Qoronfleh, MW and Chidambaram, SB and Song, BJ}, title = {Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review.}, journal = {Cells}, volume = {11}, number = {8}, pages = {}, pmid = {35456041}, issn = {2073-4409}, support = {ZIA AA000036/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Depression ; *Depressive Disorder, Major ; Dysbiosis/metabolism ; Humans ; Prebiotics ; *Synbiotics ; }, abstract = {Depression is a highly common mental disorder, which is often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated a clear correlation between gut dysbiosis (GD) or gut microbial dysbiosis and the development of anxiety or depressive behaviors. The gut microbiome communicates with the brain through the neural, immune, and metabolic pathways, either directly (via vagal nerves) or indirectly (via gut- and microbial-derived metabolites as well as gut hormones and endocrine peptides, including peptide YY, pancreatic polypeptide, neuropeptide Y, cholecystokinin, corticotropin-releasing factor, glucagon-like peptide, oxytocin, and ghrelin). Maintaining healthy gut microbiota (GM) is now being recognized as important for brain health through the use of probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), etc. A few approaches exert antidepressant effects via restoring GM and hypothalamus-pituitary-adrenal (HPA) axis functions. In this review, we have summarized the etiopathogenic link between gut dysbiosis and depression with preclinical and clinical evidence. In addition, we have collated information on the recent therapies and supplements, such as probiotics, prebiotics, short-chain fatty acids, and vitamin B12, omega-3 fatty acids, etc., which target the gut-brain axis (GBA) for the effective management of depressive behavior and anxiety.}, }
@article {pmid35455639, year = {2022}, author = {Di Domenico, M and Ballini, A and Boccellino, M and Scacco, S and Lovero, R and Charitos, IA and Santacroce, L}, title = {The Intestinal Microbiota May Be a Potential Theranostic Tool for Personalized Medicine.}, journal = {Journal of personalized medicine}, volume = {12}, number = {4}, pages = {}, pmid = {35455639}, issn = {2075-4426}, abstract = {The human intestine is colonized by a huge number of microorganisms from the moment of birth. This set of microorganisms found throughout the human body, is called the microbiota; the microbiome indicates the totality of genes that the microbiota can express, i.e., its genetic heritage. Thus, microbiota participates in and influences the proper functioning of the organism. The microbiota is unique for each person; it differs in the types of microorganisms it contains, the number of each microorganism, and the ratio between them, but mainly it changes over time and under the influence of many factors. Therefore, the correct functioning of the human body depends not only on the expression of its genes but also on the expression of the genes of the microorganisms it coexists with. This fact makes clear the enormous interest of community science in studying the relationship of the human microbiota with human health and the incidence of disease. The microbiota is like a unique personalized "mold" for each person; it differs quantitatively and qualitatively for the microorganisms it contains together with the relationship between them, and it changes over time and under the influence of many factors. We are attempting to modulate the microbial components in the human intestinal microbiota over time to provide positive feedback on the health of the host, from intestinal diseases to cancer. These interventions to modulate the intestinal microbiota as well as to identify the relative microbiome (genetic analysis) can range from dietary (with adjuvant prebiotics or probiotics) to fecal transplantation. This article researches the recent advances in these strategies by exploring their advantages and limitations. Furthermore, we aim to understand the relationship between intestinal dysbiosis and pathologies, through the research of resident microbiota, that would allow the personalization of the therapeutic antibiotic strategy.}, }
@article {pmid35453611, year = {2022}, author = {Lian, WS and Wang, FS and Chen, YS and Tsai, MH and Chao, HR and Jahr, H and Wu, RW and Ko, JY}, title = {Gut Microbiota Ecosystem Governance of Host Inflammation, Mitochondrial Respiration and Skeletal Homeostasis.}, journal = {Biomedicines}, volume = {10}, number = {4}, pages = {}, pmid = {35453611}, issn = {2227-9059}, support = {NHRI-EX110-11029SI//National Health Research Institutes/ ; CORPG8L0361, and CMRPG8K0041-43//Chang Gung Memorial Hospital/ ; }, abstract = {Osteoporosis and osteoarthritis account for the leading causes of musculoskeletal dysfunction in older adults. Senescent chondrocyte overburden, inflammation, oxidative stress, subcellular organelle dysfunction, and genomic instability are prominent features of these age-mediated skeletal diseases. Age-related intestinal disorders and gut dysbiosis contribute to host tissue inflammation and oxidative stress by affecting host immune responses and cell metabolism. Dysregulation of gut microflora correlates with development of osteoarthritis and osteoporosis in humans and rodents. Intestinal microorganisms produce metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide, and liposaccharides, affecting mitochondrial function, metabolism, biogenesis, autophagy, and redox reactions in chondrocytes and bone cells to regulate joint and bone tissue homeostasis. Modulating the abundance of Lactobacillus and Bifidobacterium, or the ratio of Firmicutes and Bacteroidetes, in the gut microenvironment by probiotics or fecal microbiota transplantation is advantageous to suppress age-induced chronic inflammation and oxidative damage in musculoskeletal tissue. Supplementation with gut microbiota-derived metabolites potentially slows down development of osteoarthritis and osteoporosis. This review provides latest molecular and cellular insights into the biological significance of gut microorganisms and primary and secondary metabolites important to cartilage and bone integrity. It further highlights treatment options with probiotics or metabolites for modulating the progression of these two common skeletal disorders.}, }
@article {pmid35453587, year = {2022}, author = {Biliński, J and Jasiński, M and Basak, GW}, title = {The Role of Fecal Microbiota Transplantation in the Treatment of Acute Graft-versus-Host Disease.}, journal = {Biomedicines}, volume = {10}, number = {4}, pages = {}, pmid = {35453587}, issn = {2227-9059}, abstract = {The number of allogeneic hematopoietic stem cell transplantations conducted worldwide is constantly rising. Together with that, the absolute number of complications after the procedure is increasing, with graft-versus-host disease (GvHD) being one of the most common. The standard treatment is steroid administration, but only 40-60% of patients will respond to the therapy and some others will be steroid-dependent. There is still no consensus regarding the best second-line option, but fecal microbiota transplantation (FMT) has shown encouraging preliminary and first clinically relevant results in recent years and seems to offer great hope for patients. The reason for treatment of steroid-resistant acute GvHD using this method derives from studies showing the significant immunomodulatory role played by the intestinal microbiota in the pathogenesis of GvHD. Depletion of commensal microbes is accountable for aggravation of the disease and is associated with decreased overall survival. In this review, we present the pathogenesis of GvHD, with special focus on the special role of the gut microbiota and its crosstalk with immune cells. Moreover, we show the results of studies and case reports to date regarding the use of FMT in the treatment of steroid-resistant acute GvHD.}, }
@article {pmid35453231, year = {2022}, author = {de Stefano, MC and Mazzanti, B and Vespasiano, F and Lombardini, L and Cardillo, M}, title = {The Regulatory Approach for Faecal Microbiota Transplantation as Treatment for Clostridioides difficile Infection in Italy.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {35453231}, issn = {2079-6382}, abstract = {Faecal microbiota transplantation (FMT) is regarded as an efficacious treatment for recurrent C. difficile infection. Unfortunately, widespread patient access is hindered by regulatory hurdles, which are the primary barriers to incorporating FMT into clinical practice. At the European and International level, there is no uniform perspective on FMT classification, and a coordinated effort is desirable to solve this regulatory puzzle. In this communication, we report the regulatory principles and the implementation approach for FMT application in Italy. Our experience suggests that the EU Tissue and Cell Directives are suited to ensure safe and efficient FMT for C. difficile management, especially through extensive high-quality donor selection and full traceability maintenance.}, }
@article {pmid35451337, year = {2022}, author = {Caira-Chuquineyra, B and Fernandez-Guzman, D and Soriano-Moreno, DR and Fernandez-Morales, J and Flores-Lovon, K and Medina-Ramírez, SA and Gonzales-Uribe, AG and Pelayo-Luis, IP and Gonzales-Zamora, JA and Huaringa-Marcelo, J}, title = {Fecal Microbiota Transplantation for People Living with Human Immunodeficiency Virus: A Scoping Review.}, journal = {AIDS research and human retroviruses}, volume = {38}, number = {9}, pages = {700-708}, doi = {10.1089/AID.2022.0016}, pmid = {35451337}, issn = {1931-8405}, mesh = {*Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; HIV ; *HIV Infections ; Humans ; Randomized Controlled Trials as Topic ; T-Lymphocytes ; Treatment Outcome ; }, abstract = {The aim of this scoping review was to determine the characteristics of studies evaluating fecal microbiota transplantation (FMT), as well as its effects and safety as a therapeutic intervention for people living with human immunodeficiency virus (HIV). We conducted a scoping review following the methodology of the Joanna Briggs Institute. We searched the following databases: PubMed, Web of Science, Scopus, Embase, Cochrane Library, and Medline until September 19, 2021. Studies that used FMT in people living with HIV and explored its effects on the health of these people were included. Two randomized and 2 uncontrolled clinical trials with a total of 55 participants were included. Participants were well-controlled HIV-infected people. Regarding microbiota changes, three studies found significant post-FMT increases in Fusobacterium, Prevotella, α-diversity, Chao index, and/or Shannon index, and/or decreases in Bacteroides. Regarding markers of intestinal damage, one study found a decrease in intestinal fatty acid binding protein post-FMT, and another study found an increase in zonulin. Other outcomes evaluated by the studies were as follows: markers of immune and inflammatory activation, markers of immunocompetence (CD4[+], and CD8[+] T lymphocytes), and HIV viral load; however, none showed significant changes. Clinical outcomes were not evaluated by these studies. Regarding the safety of FMT, only mild adverse events were appreciated. No serious adverse event was reported. The clinical evidence for FMT in people living with HIV is sparse. FMT appears to have good tolerability and, no serious adverse event has been reported so far. Further clinical trials and evaluation of clinically important biomedical outcomes for FMT in people living with HIV are needed.}, }
@article {pmid35449107, year = {2022}, author = {Wang, Y and Li, H}, title = {Gut microbiota modulation: a tool for the management of colorectal cancer.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {178}, pmid = {35449107}, issn = {1479-5876}, mesh = {*Colorectal Neoplasms/pathology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {Colorectal cancer (CRC) is the second cause of cancer death and the third most frequently diagnosed cancer. Besides the lifestyle, genetic and epigenetic alterations, and environmental factors, gut microbiota also plays a vital role in CRC development. The interruption of the commensal relationship between gut microbiota and the host could lead to an imbalance in the bacteria population, in which the pathogenic bacteria become the predominant population in the gut. Different therapeutic strategies have been developed to modify the gut immune system, prevent pathogen colonization, and alter the activity and composition of gut microbiota, such as prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT). Even though the employed strategies exhibit promising results, their translation into the clinic requires evaluating potential implications and risks, as well as assessment of their long-term effects. This study was set to review the gut microbiota imbalances and their relationship with CRC and their effects on CRC therapy, including chemotherapy and immunotherapy. More importantly, we reviewed the strategies that have been used to modulate gut microbiota, their impact on the treatment of CRC, and the challenges of each strategy.}, }
@article {pmid35446385, year = {2022}, author = {}, title = {Eshel A, Sharon I, Nagler A, et al. Origins of bloodstream infections following fecal microbiota transplantation: a strain-level analysis. Blood Adv. 2022;6(2):568-573.}, journal = {Blood advances}, volume = {6}, number = {8}, pages = {2578-2580}, doi = {10.1182/bloodadvances.2022007476}, pmid = {35446385}, issn = {2473-9537}, }
@article {pmid35446112, year = {2022}, author = {Hao, Y and Feng, Y and Yan, X and Chen, L and Ma, X and Tang, X and Zhong, R and Sun, Z and Agarwal, M and Zhang, H and Zhao, Y}, title = {Gut Microbiota-Testis Axis: FMT Mitigates High-Fat Diet-Diminished Male Fertility via Improving Systemic and Testicular Metabolome.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0002822}, pmid = {35446112}, issn = {2165-0497}, mesh = {Diet, High-Fat/adverse effects ; Fecal Microbiota Transplantation ; Fertility ; *Gastrointestinal Microbiome ; Humans ; *Infertility, Male/metabolism/therapy ; Male ; Metabolome ; Obesity/therapy ; Semen/metabolism ; Semen Analysis ; Sperm Motility ; Testis/metabolism ; }, abstract = {High-fat diet (HFD)-induced obesity is known to be associated with reduced male fertility and decreased semen quality in humans. HFD-related male infertility is a growing issue worldwide, and it is crucial to overcome this problem to ameliorate the distress of infertile couples. For the first time, we discovered that fecal microbiota transplantation (FMT) of alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) ameliorated HFD-decreased semen quality (sperm concentration: 286.1 ± 14.1 versus 217.9 ± 17.4 million/mL; sperm motility: 40.1 ± 0.7% versus 29.0 ± 0.9%), and male fertility (pregnancy rate: 87.4 ± 1.1% versus 70.2 ± 6.1%) by benefiting blood and testicular metabolome. A10-FMT improved HFD-disturbed gut microbiota by increasing gut Bacteroides (colon: 24.9 ± 1.1% versus 8.3 ± 0.6%; cecum: 10.2 ± 0.7% versus 3.6 ± 0.7%) and decreasing Mucispirillum (colon: 0.3 ± 0.1% versus 2.8 ± 0.4%; cecum: 2.3 ± 0.5% versus 6.6 ± 0.7%). A10-FMT benefited gut microbiota to improve liver function by adjusting lipid metabolism to produce n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (blood: 55.5 ± 18.7 versus 20.3 ± 2.4) and docosahexaenoic acid (testis: 121.2 ± 6.2 versus 89.4 ± 6.7), thus ameliorating HFD-impaired testicular microenvironment to rescue spermatogenesis and increase semen quality and fertility. The findings indicated that AOS-improved gut microbiota may be a promising strategy to treat obesity or metabolic issues-related male infertility in the future. IMPORTANCE HFD decreases male fertility via upsetting gut microbiota and transplantation of AOS-benefited gut microbiota (A10-FMT) improves gut microbiota to ameliorate HFD-reduced male fertility. Moreover, A10-FMT improved liver function to benefit the blood metabolome and simultaneously ameliorated the testicular microenvironment to turn the spermatogenesis process on. We demonstrated that AOS-benefited gut microbiota could be applied to treat infertile males with obesity and metabolic issues induced by HFD.}, }
@article {pmid35444617, year = {2022}, author = {Zhang, WH and Jin, ZY and Yang, ZH and Zhang, JY and Ma, XH and Guan, J and Sun, BL and Chen, X}, title = {Fecal Microbiota Transplantation Ameliorates Active Ulcerative Colitis by Downregulating Pro-inflammatory Cytokines in Mucosa and Serum.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {818111}, pmid = {35444617}, issn = {1664-302X}, abstract = {BACKGROUND: Ulcerative colitis (UC) is a multi-factor disease characterized by alternating remission periods and repeated occurrence. It has been shown that fecal microbiota transplantation (FMT) is an emerging and effective approach for UC treatment. Since most existing studies chose adults as donors for fecal microbiota, we conducted this study to determine the long-term efficacy and safety of the microbiota from young UC patient donors and illustrate its specific physiological effects.<br><br>METHODS: Thirty active UC patients were enrolled and FMT were administered with the first colonoscopy and two subsequent enema/transendoscopic enteral tubing (TET) practical regimens in The First Affiliated Hospital of Anhui Medical University in China. Disease activity and inflammatory biomarkers were assessed 6&#x2009;weeks/over 1&#x2009;year after treatment. The occurrence of adverse events was also recorded. The samples from blood and mucosa were collected to detect the changes of inflammatory biomarkers and cytokines. The composition of gut and oral microbiota were also sampled and sequenced to confirm the alteration of microbial composition.<br><br>RESULTS: Twenty-seven patients completed the treatment, among which 16 (59.3%) achieved efficacious clinical response and 11 (40.7%) clinical remission. Full Mayo score and calprotectin dropped significantly and remained stable over 1&#x2009;year. FMT also significantly reduced the levels of C-reactive protein (CRP), interleukin-1 beta (IL-1&#x3b2;), and interleukin-6 (IL-6). The gut microbiota altered significantly with increased bacterial diversity and decreased metabolic diversity in responsive patients. The pro-inflammatory enterobacteria decreased after FMT and the abundance of Collinsella increased. Accordingly, the altered metabolic functions, including antigen synthesis, amino acids metabolism, short chain fatty acid production, and vitamin K synthesis of microbiota, were also corrected by FMT.<br><br>CONCLUSION: Fecal microbiota transplantation seems to be safe and effective for active UC patients who are nonresponsive to mesalazine or prednisone in the long-term. FMT could efficiently downregulate pro-inflammatory cytokines to ameliorate the inflammation.}, }
@article {pmid35439340, year = {2022}, author = {Wang, HG and Zhang, MN and Wen, X and He, L and Zhang, MH and Zhang, JL and Yang, XZ}, title = {Cepharanthine ameliorates dextran sulphate sodium-induced colitis through modulating gut microbiota.}, journal = {Microbial biotechnology}, volume = {15}, number = {8}, pages = {2208-2222}, pmid = {35439340}, issn = {1751-7915}, mesh = {Animals ; Benzylisoquinolines ; *Colitis/drug therapy/therapy ; *Colitis, Ulcerative/chemically induced/drug therapy ; Colon ; Cytokines/metabolism ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Cepharanthine (CEP) is an active alkaloid isolated from Stephania Cepharantha Hayata. It is reported that the anti-inflammatory properties of CEP could be employed to treat a variety of diseases. In this study, we first found that CEP ameliorates ulcerative colitis (UC) induced by DSS. The effect of CEP on gut microbiota was further evaluated by 16S rRNA gene sequencing, antibiotic pretreatment and faecal microbiota transplantation (FMT). Results showed that the abundances of gut microbiota, such as Romboutsia, Turicibacter and Escherichia-Shigella (especially Romboutsia), were significantly reduced after CEP treatment. Additionally, we explored the mechanisms of CEP by a strategy integrating transcriptomics with network pharmacology. The transcriptome data confirmed that CEP functioned through cytokine and cytokine receptor pathways. The expression levels of 10 pro-inflammatory hub genes (such as CXCL1, CXCL9, CCL7) were positively correlated with the abundance of Romboutsia. Our data identified Romboutsia as a potential pathobiont in UC. Collectively, we confirmed that CEP relieved colon inflammation by modulating gut microbiota and pro-inflammatory cytokine expression. CEP can be adopted to design novel effective therapeutic strategies for UC.}, }
@article {pmid35438589, year = {2022}, author = {Lan, J and Zhang, H and Zhao, H and Liu, L and Shi, Q and Li, D and Ju, X}, title = {Cord Blood Natural Killer Cells Inhibit Sepsis Caused by Feces-Induced Acute Peritonitis via Increasing Endothelium Integrity.}, journal = {Cell transplantation}, volume = {31}, number = {}, pages = {9636897221090257}, pmid = {35438589}, issn = {1555-3892}, mesh = {Animals ; Endothelial Cells ; Endothelium ; Feces ; Fetal Blood ; Killer Cells, Natural ; Lipopolysaccharides/toxicity ; Mice ; Mice, Inbred C57BL ; *Peritonitis/chemically induced/metabolism ; *Sepsis/therapy ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {Sepsis is associated with acute peritonitis, which can be induced by lipopolysaccharide exposure and feces. Generally, lipopolysaccharide induces mono-microbial peritonitis, whereas feces cause poly-microbial peritonitis; the latter is a more complicated and closer to the clinical diseases. Although several reports have discussed the mechanism of immune response in peritonitis-induced sepsis, however, the role of natural killer (NK) cells in sepsis, especially the relationship between NK cells and stabilization of the vascular endothelial barrier, is still unclear. Accordingly, in this study, we assessed the roles of NK cells in an acute sepsis model in mice. NK cells were injected via the tail vein into mice with acute sepsis, and nitric oxide (NO), anti-inflammatory cytokine, and angiogenic factors were tested to explore the effects of NK cells on sepsis. The survival rate of septic model mice infused with NK cells was significantly improved compared with the control group. Interestingly, the levels of NO, interleukin-10, and vascular endothelial growth factor (VEGF) decreased in NK cells therapy group. After the injection of NK cells, CD31 positive endothelial cells significantly increased in the kidneys and liver, although the expression of VEGF, ANGPT-1, and ET-1 was downregulated. Consistent with our hypothesis, the transfusion of NK cells into mice with sepsis blocked inflammation and increased endothelium integrity. Overall, these findings suggest that NK cells may block sepsis by modulating the VEGF pathway.}, }
@article {pmid35436585, year = {2022}, author = {Paasch, C and Bruckert, L and Soeder, S and Von Frankenberg, J and Mantke, R and Lorenz, E and Andric, M and Wiede, A and Strack, A and Hünerbein, M and Croner, S}, title = {The effect of biofeedback pelvic floor training with ACTICORE1 on fecal incontinence A prospective multicentric cohort pilot study.}, journal = {International journal of surgery (London, England)}, volume = {101}, number = {}, pages = {106617}, doi = {10.1016/j.ijsu.2022.106617}, pmid = {35436585}, issn = {1743-9159}, mesh = {Biofeedback, Psychology ; Exercise Therapy/methods ; *Fecal Incontinence/therapy ; Female ; Humans ; Male ; Pelvic Floor ; Pilot Projects ; Prospective Studies ; Quality of Life ; Treatment Outcome ; }, abstract = {INTRODUCTION: Fecal incontinence refers to the inability to pass stool in a localized and timely manner resulting in the involuntary loss of intestinal contents such as air, intestinal mucus or stool. The prevalence of fecal incontinence in the general population is approximately 2-21%. Women are more frequently affected than men. Physiotherapeutically guided pelvic floor training, otherwise known as Kegel exercise, is the mainstay of treatment for fecal incontinence. The objective of this study was to evaluate the feasibility and potential benefits of a new biofeedback training, which uses a non-insertable pelvic floor sensor with digital interface, called ACTICORE1.<br><br>METHODS: From January 2020 to April 2021, we conducted a prospective non-randomized multicentric clinical pilot study at the Alexianer St. Hedwig Hospital Berlin (Germany), private clinic Strack (Germany) and the University Hospital Magdeburg (Germany). Patients with fecal incontinence, defined as a Wexner score >2, were recruited and asked to either perform biofeedback training with ACTICORE1 (6&#xa0;min daily for 16 weeks) or daily Kegel exercise (Physiotherapeutic guidance weekly for the first 6 weeks; biweekly for the remaining 10 weeks). The primary outcome was severity of fecal incontinence after 16 weeks of training assessed using the Wexner score. Secondary outcomes were severity of fecal incontinence after 12 weeks and patients' quality of life assessed using the EQ-5D-3L questionnaire after 16 weeks of training. The two-one-sided t-tests (TOST) procedure was used to determine if training with ACTICORE1 has equivalent or noninferior efficacies compared to Kegel exercise.<br><br>RESULTS: A total of 40 individuals were included. Dropout occurred in 4 cases. The final sample included 19 patients who performed the ACTICORE1 training (ACTICORE-group) and 17 patients who performed guideline-based physiotherapy (PHYSIO-group). Univariate analysis of biometric parameters showed no statistically significant differences. Individuals in the ACTICORE-group were younger (M=46,6 (SD=18,9) years vs. M=57,1 (SD=17,3) years, p=0.093). In terms of endpoint evaluation, a non-inferiority of ACTICORE1 compared to the therapy standard (Kegel exercise) was detected. Both groups showed a statistically significant intraindividual improvement in fecal incontinence as measured by Wexner scoring after 16 weeks. The TOST detected a non-inferiority of ACTICORE1 training (98% confidence interval with equivalence bounds 5 for low and high; Results: 1.36, upper 6.75).<br><br>CONCLUSION: Pelvic floor training with ACTICORE1 may enable sufficient pelvic floor training as a digital health application. The study at hand revealed a non-inferiority of ACTICORE1 training compared to Kegel exercise.}, }
@article {pmid35435504, year = {2022}, author = {Deng, L and Wojciech, L and Png, CW and Koh, EY and Aung, TT and Kioh, DYQ and Chan, ECY and Malleret, B and Zhang, Y and Peng, G and Gascoigne, NRJ and Tan, KSW}, title = {Experimental colonization with Blastocystis ST4 is associated with protective immune responses and modulation of gut microbiome in a DSS-induced colitis mouse model.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {79}, number = {5}, pages = {245}, pmid = {35435504}, issn = {1420-9071}, support = {R-571-000-037-114//NUHS Seed Grant/ ; R-571-000-061-114//NUHS Seed Grant/ ; R-148-000-277-114//NUS Research Grant/ ; CPF2017-12//Chengdu Giant Panda Breeding Research Foundation/ ; }, mesh = {Animals ; Bacteria ; *Blastocystis ; *Colitis/chemically induced ; Cytokines ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Immunity ; Mice ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Blastocystis is a common gut protistan parasite in humans and animals worldwide, but its interrelationship with the host gut microbiota and mucosal immune responses remains poorly understood. Different murine models of Blastocystis colonization were used to examine the effect of a common Blastocystis subtype (ST4) on host gut microbial community and adaptive immune system.<br><br>RESULTS: Blastocystis ST4-colonized normal healthy mice and Rag1[-/-] mice asymptomatically and was able to alter the microbial community composition, mainly leading to increases in the proportion of Clostridia vadinBB60 group and Lachnospiraceae NK4A136 group, respectively. Blastocystis ST4 colonization promoted T helper 2 (Th2) response defined by interleukin (IL)-5 and IL-13 cytokine production, and T regulatory (Treg) induction from colonic lamina propria in normal healthy mice. Additionally, we observed that Blastocystis ST4 colonization can maintain the stability of bacterial community composition and induce Th2 and Treg immune responses to promote faster recovery from experimentally induced colitis. Furthermore, fecal microbiota transplantation of Blastocystis ST4-altered gut microbiome to colitis mice reduced the severity of colitis, which was associated with increased production of short-chain fat acids (SCFAs) and anti-inflammatory cytokine IL-10.<br><br>CONCLUSIONS: The data confirm our hypothesis that Blastocystis ST4 is a beneficial commensal, and the beneficial effects of Blastocystis ST4 colonization is mediated through modulating of the host gut bacterial composition, SCFAs production, and Th2 and Treg responses in different murine colonization models.}, }
@article {pmid35435140, year = {2022}, author = {Debédat, J and Le Roy, T and Voland, L and Belda, E and Alili, R and Adriouch, S and Bel Lassen, P and Kasahara, K and Hutchison, E and Genser, L and Torres, L and Gamblin, C and Rouault, C and Zucker, JD and Kapel, N and Poitou, C and Marcelin, G and Rey, FE and Aron-Wisnewsky, J and Clément, K}, title = {The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2050635}, pmid = {35435140}, issn = {1949-0984}, mesh = {Animals ; Bacteroidetes ; Body Weight ; *Diabetes Mellitus, Type 2/microbiology ; *Gastric Bypass/methods ; *Gastrointestinal Microbiome ; Humans ; Mice ; Weight Loss ; }, abstract = {Roux-en-Y gastric bypass (RYGB) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes (T2D) improvements in patients with severe obesity and T2D. We hypothesized a causal implication of the gut microbiota (GM) in these metabolic benefits, as RYGB is known to deeply impact its composition. In a cohort of 100 patients with baseline T2D who underwent RYGB and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their T2D (Severe vs Mild) throughout the follow-up. We identified via nanopore-based GM sequencing that the more severe cases of unresolved T2D were associated with a major increase of the class Bacteroidia, including 12 species comprising Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals' metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.}, }
@article {pmid35434820, year = {2022}, author = {Stenberg, R and Brummer, RJ and Norén, T}, title = {Faecal transplantation in a two-year-old child with therapy-resistant Clostridiodes difficileinfection.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {111}, number = {8}, pages = {1628-1629}, pmid = {35434820}, issn = {1651-2227}, mesh = {Child, Preschool ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid35434682, year = {2022}, author = {Natarajan, A and Zlitni, S and Brooks, EF and Vance, SE and Dahlen, A and Hedlin, H and Park, RM and Han, A and Schmidtke, DT and Verma, R and Jacobson, KB and Parsonnet, J and Bonilla, HF and Singh, U and Pinsky, BA and Andrews, JR and Jagannathan, P and Bhatt, AS}, title = {Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection.}, journal = {Med (New York, N.Y.)}, volume = {3}, number = {6}, pages = {371-387.e9}, pmid = {35434682}, issn = {2666-6340}, support = {R01 AI148623/AI/NIAID NIH HHS/United States ; K24 AI144048/AI/NIAID NIH HHS/United States ; K23 AI076614/AI/NIAID NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; T32 AI052073/AI/NIAID NIH HHS/United States ; U01 AI150741/AI/NIAID NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {*COVID-19/diagnosis ; COVID-19 Testing ; *Communicable Diseases ; Feces ; *Gastrointestinal Diseases/diagnosis ; Humans ; Lung ; RNA, Viral/genetics ; SARS-CoV-2/genetics ; }, abstract = {BACKGROUND: COVID-19 manifests with respiratory, systemic, and gastrointestinal (GI) symptoms.[1][,] SARS-CoV-2 RNA is detected in respiratory and fecal samples, and recent reports demonstrate viral replication in both the lung and intestinal tissue.2, 3, 4 Although much is known about early fecal RNA shedding, little is known about long-term shedding, especially in those with mild COVID-19. Furthermore, most reports of fecal RNA shedding do not correlate these findings with GI symptoms.[5].<br><br>METHODS: We analyzed the dynamics of fecal RNA shedding up to 10&#xa0;months after COVID-19 diagnosis in 113 individuals with mild to moderate disease. We also correlated shedding with disease symptoms.<br><br>FINDINGS: Fecal SARS-CoV-2 RNA is detected in 49.2% [95% confidence interval, 38.2%-60.3%] of participants within the first week after diagnosis. Whereas there was no ongoing oropharyngeal SARS-CoV-2 RNA shedding in subjects at 4&#xa0;months, 12.7% [8.5%-18.4%] of participants continued to shed SARS-CoV-2 RNA in the feces at 4&#xa0;months after diagnosis and 3.8% [2.0%-7.3%] shed at 7&#xa0;months. Finally, we found that GI symptoms (abdominal pain, nausea, vomiting) are associated with fecal shedding of SARS-CoV-2 RNA.<br><br>CONCLUSIONS: The extended presence of viral RNA in feces, but not in respiratory samples, along with the association of fecal viral RNA shedding with GI symptoms suggest that SARS-CoV-2 infects the GI tract and that this infection can be prolonged in a subset of individuals with COVID-19.<br><br>FUNDING: This research was supported by a Stanford ChemH-IMA grant; fellowships from the AACR and NSF; and NIH R01-AI148623, R01-AI143757, and UL1TR003142.}, }
@article {pmid35433249, year = {2022}, author = {Madan, N and Quintiliani, S and Patel, P and Patel, V}, title = {The tale of the traveling cheese: Shigella in a lung transplant patient.}, journal = {Respiratory medicine case reports}, volume = {37}, number = {}, pages = {101645}, pmid = {35433249}, issn = {2213-0071}, abstract = {Shigellae are Gram-negative, nonmotile, facultatively anaerobic, non-spore-forming rods. Shigella is a common cause of gastroenteritis in areas of overcrowding and poor sanitation, but is seen less frequently in the developed world. Infection is mainly acquired through the fecal-oral route, but consumption of unpasteurized dairy remains a high risk for transmission. In the developing world, Shigella is a childhood illness and with adequate hydration is fairly self-limiting. The use of antibiotics depends on the severity of illness, the age of the patient and immune status. In immunocompromised patients, chronic symptomatic or relapsing infection has been described. In this report, we describe a case of a lung transplant patient, one year out of his transplant, on triple immunosuppressive therapy, who presented with septic shock secondary to Shigella gastroenteritis after ingesting unpasteurized cheese brought back from Peru. This case highlights the importance of educating transplant patients on how to reduce certain harmful exposures that may be fatal in immunosuppressed individuals.}, }
@article {pmid35432306, year = {2022}, author = {Jasiński, M and Biliński, J and Basak, GW}, title = {The Role of the Crosstalk Between Gut Microbiota and Immune Cells in the Pathogenesis and Treatment of Multiple Myeloma.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {853540}, pmid = {35432306}, issn = {1664-3224}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immune System/physiology ; *Multiple Myeloma/therapy ; Neoplasm Recurrence, Local ; }, abstract = {Around 10% of all hematologic malignancies are classified as multiple myeloma (MM), the second most common malignancy within that group. Although massive progress in developing of new drugs against MM has been made in recent years, MM is still an incurable disease, and every patient eventually has relapse refractory to any known treatment. That is why further and non-conventional research elucidating the role of new factors in MM pathogenesis is needed, facilitating discoveries of the new drugs. One of these factors is the gut microbiota, whose role in health and disease is still being explored. This review presents the continuous changes in the gut microbiota composition during our whole life with a particular focus on its impact on our immune system. Additionally, it mainly focuses on the chronic antigenic stimulation of B-cells as the leading mechanism responsible for MM promotion. The sophisticated interactions between microorganisms colonizing our gut, immune cells (dendritic cells, macrophages, neutrophils, T/B cells, plasma cells), and intestinal epithelial cells will be shown. That article summarizes the current knowledge about the initiation of MM cells, emphasizing the role of microorganisms in that process.}, }
@article {pmid35432269, year = {2022}, author = {Qu, L and Cheng, Q and Wang, Y and Mu, H and Zhang, Y}, title = {COPD and Gut-Lung Axis: How Microbiota and Host Inflammasome Influence COPD and Related Therapeutics.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {868086}, pmid = {35432269}, issn = {1664-302X}, abstract = {The exact pathogenesis of chronic obstructive pulmonary disease (COPD) remains largely unknown. While current management strategies are effective at stabilizing the disease or relief the symptoms, new approaches are required to target underlying disease process and reverse lung function deterioration. Recent research showed that pneumonia bacteria is critical in disease progression and gut microbiome is likely perturbed in COPD, which is usually accompanied by a decreased intestinal microbial diversity and a disturbance in immune system, contributing to a chronic inflammation. The cross-talk between gut microbes and lungs, termed as the "gut-lung axis," is known to impact immune response and homeostasis in the airway. Although the gut and respiratory microbiota exhibit compositional differences, the gut and lung showed similarities in the origin of epithelia of both gastrointestinal and respiratory tracts, the anatomical structure, and early-life microbial colonization. Evidence showed that respiratory infection might be prevented, or at least dampened by regulating gut microbial ecosystem; thus, a promising yet understudied area of COPD management is nutrition-based preventive strategies. COPD patient is often deficient in nutrient such as antioxidant, vitamins, and fiber intake. However, further larger-scale randomized clinical trials (RCTs) are required to establish the role of these nutrition-based diet in COPD management. In this review, we highlight the important and complex interaction of microbiota and immune response on gut-lung axis. Further research into the modification and improvement of the gut microbiota and new interventions through diet, probiotics, vitamins, and fecal microbiota transplantation is extreme critical to provide new preventive therapies for COPD.}, }
@article {pmid35431515, year = {2022}, author = {Marascio, N and Rotundo, S and Quirino, A and Matera, G and Liberto, MC and Costa, C and Russo, A and Trecarichi, EM and Torti, C}, title = {Similarities, differences, and possible interactions between hepatitis E and hepatitis C viruses: Relevance for research and clinical practice.}, journal = {World journal of gastroenterology}, volume = {28}, number = {12}, pages = {1226-1238}, pmid = {35431515}, issn = {2219-2840}, mesh = {Antiviral Agents/therapeutic use ; Female ; Hepacivirus/genetics ; *Hepatitis C/complications/diagnosis/drug therapy ; *Hepatitis C, Chronic/drug therapy ; *Hepatitis E/complications/diagnosis/drug therapy ; *Hepatitis E virus/genetics ; Humans ; Phylogeny ; Pregnancy ; }, abstract = {Hepatitis E virus (HEV) and hepatitis C virus (HCV) are both RNA viruses with a tropism for liver parenchyma but are also capable of extrahepatic manifestations. Hepatitis E is usually a viral acute fecal-oral transmitted and self-limiting disease presenting with malaise, jaundice, nausea and vomiting. Rarely, HEV causes a chronic infection in immunocompromised persons and severe fulminant hepatitis in pregnant women. Parenteral HCV infection is typically asymptomatic for decades until chronic complications, such as cirrhosis and cancer, occur. Despite being two very different viruses in terms of phylogenetic and clinical presentations, HEV and HCV show many similarities regarding possible transmission through organ transplantation and blood transfusion, pathogenesis (production of antinuclear antibodies and cryoglobulins) and response to treatment with some direct-acting antiviral drugs. Although both HEV and HCV are well studied individually, there is a lack of knowledge about coinfection and its consequences. The aim of this review is to analyze current literature by evaluating original articles and case reports and to hypothesize some interactions that can be useful for research and clinical practice.}, }
@article {pmid35431512, year = {2022}, author = {Hong, Y and Zhao, J and Chen, YR and Huang, ZH and Hou, LD and Shen, B and Xin, Y}, title = {Spinal anesthesia alleviates dextran sodium sulfate-induced colitis by modulating the gut microbiota.}, journal = {World journal of gastroenterology}, volume = {28}, number = {12}, pages = {1239-1256}, pmid = {35431512}, issn = {2219-2840}, mesh = {*Anesthesia, Spinal/adverse effects ; *Anesthetics/adverse effects ; Animals ; Bacteroidetes ; *Colitis/drug therapy/therapy ; Colon ; Dextran Sulfate/toxicity ; Disease Models, Animal ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases ; Mice ; Mice, Inbred C57BL ; Sulfates ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease with recurrent intestinal inflammation. Although the exact etiology of IBD remains unknown, the accepted hypothesis of the pathogenesis to date is that abnormal immune responses to the gut microbiota are caused by environmental factors. The role of the gut microbiota, particularly the bidirectional interaction between the brain and gut microbiota, has gradually attracted more attention.<br><br>AIM: To investigate the potential effect of spinal anesthesia on dextran sodium sulfate (DSS)-induced colitis mice and to detect whether alterations in the gut microbiota would be crucial for IBD.<br><br>METHODS: A DSS-induced colitis mice model was established. Spinal anesthesia was administered on colitis mice in combination with the methods of cohousing and fecal microbiota transplantation (FMT) to explore the role of spinal anesthesia in IBD and identify the potential mechanisms involved.<br><br>RESULTS: We demonstrated that spinal anesthesia had protective effects against DSS-induced colitis by alleviating clinical symptoms, including reduced body weight loss, decreased disease activity index score, improved intestinal permeability and colonic morphology, decreased inflammatory response, and enhanced intestinal barrier functions. Moreover, spinal anesthesia significantly increased the abundance of Bacteroidetes, which was suppressed in the gut microbiota of colitis mice. Interestingly, cohousing with spinal anesthetic mice and FMT from spinal anesthetic mice can also alleviate DSS-induced colitis by upregulating the abundance of Bacteroidetes. We further showed that spinal anesthesia can reduce the increase in noradrenaline levels induced by DSS, which might affect the gut microbiota.<br><br>CONCLUSION: These data suggest that microbiota dysbiosis may contribute to IBD and provide evidence supporting the protective effects of spinal anesthesia on IBD by modulating the gut microbiota, which highlights a novel approach for the treatment of IBD.}, }
@article {pmid35430804, year = {2022}, author = {Xiao, W and Su, J and Gao, X and Yang, H and Weng, R and Ni, W and Gu, Y}, title = {The microbiota-gut-brain axis participates in chronic cerebral hypoperfusion by disrupting the metabolism of short-chain fatty acids.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {62}, pmid = {35430804}, issn = {2049-2618}, mesh = {Animals ; *Brain-Gut Axis ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Mice, Inbred C57BL ; Rats ; Mice ; }, abstract = {BACKGROUND: Chronic cerebral hypoperfusion (CCH) underlies secondary brain injury following certain metabolic disorders and central nervous system (CNS) diseases. Dysregulation of the microbiota-gut-brain axis can exacerbate various CNS disorders through aberrantly expressed metabolites such as short-chain fatty acids (SCFAs). Yet, its relationship with CCH remains to be demonstrated. And if so, it is of interest to explore whether restoring gut microbiota to maintain SCFA metabolism could protect against CCH.<br><br>RESULTS: Rats subjected to bilateral common carotid artery occlusion (BCCAO) as a model of CCH exhibited cognitive impairment, depressive-like behaviors, decreased gut motility, and compromised gut barrier functions. The 16S ribosomal RNA gene sequencing revealed an abnormal gut microbiota profile and decreased relative abundance of some representative SCFA producers, with the decreased hippocampal SCFAs as the further evidence. Using fecal microbiota transplantation (FMT), rats recolonized with a balanced gut microbiome acquired a higher level of hippocampal SCFAs, as well as decreased neuroinflammation when exposed to lipopolysaccharide. Healthy FMT promoted gut motility and gut barrier functions, and improved cognitive decline and depressive-like behaviors by inhibiting hippocampal neuronal apoptosis in BCCAO rats. Long-term SCFA supplementation further confirmed its neuroprotective effect in terms of relieving inflammatory response and hippocampal neuronal apoptosis following BCCAO.<br><br>CONCLUSION: Our results demonstrate that modulating the gut microbiome via FMT can ameliorate BCCAO-induced gut dysbiosis, cognitive decline, and depressive-like behaviors, possibly by enhancing the relative abundance of SCFA-producing floras and subsequently increasing SCFA levels. Video abstract.}, }
@article {pmid35426646, year = {2022}, author = {Adams, SM and Close, ED and Shreenath, AP}, title = {Ulcerative Colitis: Rapid Evidence Review.}, journal = {American family physician}, volume = {105}, number = {4}, pages = {406-411}, pmid = {35426646}, issn = {1532-0650}, mesh = {Antibodies, Anti-Idiotypic ; *Colitis, Ulcerative/diagnosis/therapy ; Fecal Microbiota Transplantation ; Humans ; Inflammation ; Leukocyte L1 Antigen Complex ; }, abstract = {Ulcerative colitis is a relapsing and remitting inflammatory bowel disease of the large intestine. Risk factors include recent Salmonella or Campylobacter infection and a family history of ulcerative colitis. Diagnosis is suspected based on symptoms of urgency, tenesmus, and hematochezia and is confirmed with endoscopic findings of continuous inflammation from the rectum to more proximal colon, depending on the extent of disease. Fecal calprotectin may be used to assess disease activity and relapse. Medications available to treat the inflammation include 5-aminosalicylic acid, corticosteroids, tumor necrosis factor-alpha antibodies, anti-integrin antibodies, anti-interleukin-12 and -23 antibodies, and Janus kinase inhibitors. Choice of medication and method of delivery depend on the location and severity of mucosal inflammation. Other treatments such as fecal microbiota transplantation are considered experimental, and complementary therapies such as probiotics and curcumin have mixed data. Surgical treatment may be needed for fulminant or refractory disease. Increased risk of colorectal cancer and use of immunosuppressive therapies affect the preventive care needs for these patients.}, }
@article {pmid35421383, year = {2022}, author = {Sepahvand, F and Mamaghani, AJ and Ezatpour, B and Badparva, E and Zebardast, N and Fallahi, S}, title = {Gastrointestinal parasites in immunocompromised patients; A comparative cross-sectional study.}, journal = {Acta tropica}, volume = {231}, number = {}, pages = {106464}, doi = {10.1016/j.actatropica.2022.106464}, pmid = {35421383}, issn = {1873-6254}, mesh = {*Acquired Immunodeficiency Syndrome/complications ; Animals ; Cross-Sectional Studies ; *Cryptosporidiosis/complications ; *Cryptosporidium ; Feces/parasitology ; Humans ; Immunocompromised Host ; *Intestinal Diseases, Parasitic/parasitology ; Middle Aged ; *Parasites ; Prevalence ; }, abstract = {Gastrointestinal parasites (GIPs), including helminths and protozoa species, are a major health problem in many parts of the world. About 3.5 billion people are affected by the parasites worldwide. GIPs are one of the leading causes of death among immunocompromised individuals and can cause serious clinical complications, especially in people with Human Immunodeficiency Virus (HIV)/AIDS, hemodialysis patients, and transplant recipients. This study aimed to compare the prevalence of GIPs among immunocompromised patients and immunocompetent individuals in Lorestan province, West Iran. In the current study, with a sampling of 232 participants (114 hemodialysis, AIDS, and organ transplantation immunocompromised patients and 118 immunocompetent individuals as the control group), demographic characteristics and risk factors for GIPs were collected through a pre-designed questionnaire. Stool samples of patients and the control group were examined for GIPs using different diagnostic methods including direct smear (saline and Lugol's iodine), Ziehl-Neelsen staining, agar-plate culture, and concentration method (formalin ether sedimentation). To evaluate the relative status of the immune system, TCD4[+] cells were counted in the blood samples of the subjects by flow cytometry. The results were analyzed using SPSS 21 software, Fisher exact, and chi-square statistical tests. Multivariate modeling of the data was performed using logistic regression. The prevalence of GIPs in immunocompromised patients was more than twice that of immunocompetent individuals in the control group (42.06% vs. 17.79%). The most prevalent parasites identified among immunocompromised patients were Cryptosporidium sp. (27.1%), Blastocystis sp. (16.7%), and Entamoeba coli (14.6%) respectively. Cryptosporidium sp. had the highest frequency among hemodialysis patients (6.49%), AIDS patients (26.92%), and transplant recipients (18.18%) respectively. Patients with AIDS had the highest positive results for Cryptosporidium sp. followed by Microsporidia sp. (23.7%). In immunocompetent individuals, the highest prevalence of GIPs was related to Blastocystis sp and Trichomonas hominis (28.57%). Statistical analysis of the data showed that there was a statistically significant difference between various age groups regarding infection with GIPs so the highest rate of GIPs infection was observed in the age group lower than 50 years (P = 0.035). The statistical difference between the variable of location and infection with GIPs was insignificant but remarkable (P = 0.070). According to the results, it can be concluded that GIP is more common in immunocompromised patients than in immunocompetent individuals with cryptosporidium sp. predominance. Due to the favorable conditions of immunocompromised patients for GIPs and considering them as one of the important sources of parasitic infections and parasite transmission in society, control, prevention, and monitoring of their social behaviors along with health issues are inevitable.}, }
@article {pmid35421353, year = {2022}, author = {Dsouza, M and Menon, R and Crossette, E and Bhattarai, SK and Schneider, J and Kim, YG and Reddy, S and Caballero, S and Felix, C and Cornacchione, L and Hendrickson, J and Watson, AR and Minot, SS and Greenfield, N and Schopf, L and Szabady, R and Patarroyo, J and Smith, W and Harrison, P and Kuijper, EJ and Kelly, CP and Olle, B and Bobilev, D and Silber, JL and Bucci, V and Roberts, B and Faith, J and Norman, JM}, title = {Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {4}, pages = {583-598.e8}, doi = {10.1016/j.chom.2022.03.016}, pmid = {35421353}, issn = {1934-6069}, mesh = {*Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Healthy Volunteers ; Humans ; *Microbiota ; }, abstract = {Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and clinical efficacy. Live biotherapeutic products (LBPs) consisting of defined consortia of clonal bacterial isolates have been proposed as an alternative therapeutic class because of their promising preclinical results and safety profile. We describe VE303, an LBP comprising 8 commensal Clostridia strains under development for rCDI, and its early clinical development in healthy volunteers (HVs). In a phase 1a/b study in HVs, VE303 is determined to be safe and well-tolerated at all doses tested. VE303 strains optimally colonize HVs if dosed over multiple days after vancomycin pretreatment. VE303 promotes the establishment of a microbiota community known to provide colonization resistance.}, }
@article {pmid35421334, year = {2022}, author = {Severyn, CJ}, title = {Find a little help from my (microbial) friends.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {4}, pages = {420-422}, doi = {10.1016/j.chom.2022.03.024}, pmid = {35421334}, issn = {1934-6069}, mesh = {*Clostridioides difficile ; *Clostridium Infections/prevention &amp; control ; Fecal Microbiota Transplantation ; Friends ; Humans ; *Microbiota ; }, abstract = {Modulation of the microbiota to improve clinical outcomes remains challenging partially because of the large variability in biotherapeutic composition. In this issue of Cell Host &amp; Microbe, Dsouza and colleagues present the phase 1 study results of a defined microbial consortia developed for the prevention of recurrent Clostridioides difficile infection (CDI).}, }
@article {pmid35421277, year = {2022}, author = {Asadi, A and Shadab Mehr, N and Mohamadi, MH and Shokri, F and Heidary, M and Sadeghifard, N and Khoshnood, S}, title = {Obesity and gut-microbiota-brain axis: A narrative review.}, journal = {Journal of clinical laboratory analysis}, volume = {36}, number = {5}, pages = {e24420}, pmid = {35421277}, issn = {1098-2825}, mesh = {Brain ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; Obesity/metabolism ; Prebiotics ; }, abstract = {INTRODUCTION: Obesity is a major health problem that is associated with many physiological and mental disorders, such as diabetes, stroke, and depression. Gut microbiota has been affirmed to interact with various organs, including the brain. Intestinal microbiota and their metabolites might target the brain directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms, and they can regulate metabolism, adiposity, homoeostasis and energy balance, and central appetite and food reward signaling, which together have crucial roles in obesity. Studies support the concept of bidirectional signaling within the gut-brain axis (GBA) in the pathophysiology of obesity, mediated by metabolic, endocrine, neural, and immune system mechanisms.<br><br>MATERIALS AND METHODS: Scopus, PubMed, Google Scholar, and Web of Science databases were searched to find relevant studies.<br><br>RESULTS: The gut-brain axis (GBA), a bidirectional connection between the gut microbiota and brain, influences physiological function and behavior through three different pathways. Neural pathway mainly consists of the enteric nervous system (ENS) and vagus nerve. Endocrine pathway, however, affects the neuroendocrine system of the brain, particularly the hypothalamus-pituitary-adrenal (HPA) axis and immunological pathway. Several alterations in the gut microbiome can lead to obesity, by modulating metabolic pathways and eating behaviors of the host through GBA. Therefore, novel therapies targeting the gut microbiome, i.e., fecal microbiota transplantation and supplementation with probiotics and prebiotics, can be a potential treatment for obesity.<br><br>CONCLUSION: This study corroborates the effect of gut microbiome on physiological function and body weight. The results show that the gut microbiota is becoming a target for new antiobesity therapies.}, }
@article {pmid35419402, year = {2022}, author = {Grossi, U and Romano, M and Rossi, S and Gallo, G and Picciariello, A and Felice, C and Trojan, D and Montagner, G and Zanus, G}, title = {Anal Fistula Human Amniotic Membrane Endosealing (F-HAME): A Proof of Concept Study.}, journal = {Frontiers in surgery}, volume = {9}, number = {}, pages = {869923}, pmid = {35419402}, issn = {2296-875X}, abstract = {The treatment of cryptoglandular anal fistula (AF) is often a challenge for surgeons. Several sphincter-saving procedures have been described as an alternative to fistulotomy, with the common goal of promoting healing and preserve anal continence. The aim of this proof of concept study was to assess the outcomes of human amniotic membrane (HAM) implantation in cryptoglandular transphincteric AF. Two consecutive female were recruited. The primary outcome was clinical healing at 6 months. Secondary outcomes were ultrasonographic healing, complications and reinterventions, AF symptoms, fecal incontinence, psychological impact of treatment, recurrence, development of additional AF, patient satisfaction, and quality of life, as measured using validated questionnaires. Both patients (40 and 54-year-old) previously underwent incision and drainage of anal abscess with concomitant seton placement. HAM implantation was performed as a day case under local anesthesia. No intra- or post-procedural complications occurred. Clinical and radiological healing were not achieved at 6 months. However, the external outlet discharge diminished through time, with sustained improvements in quality of life. Clinical healing occurred at 7 months in both patients. Psychological impact of treatment and patient satisfaction were overall good, with improvements in the PHQ-9, GAD-7, and Short Assessment of Patients Satisfaction. HAM implantation is safe and improves patients' quality of life, progressively leading to clinical healing. Future studies are needed to assess its safety in other etiology of AF.}, }
@article {pmid35418976, year = {2022}, author = {Wang, J and Zhang, H and He, J and Xiong, X}, title = {The Role of the Gut Microbiota in the Development of Ischemic Stroke.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {845243}, pmid = {35418976}, issn = {1664-3224}, mesh = {Central Nervous System ; *Gastrointestinal Microbiome/physiology ; Humans ; *Ischemic Stroke/etiology ; *Nervous System Diseases ; Risk Factors ; }, abstract = {An increasing number of studies have focused on the gut microbiota and its relationship with various neurological diseases. The gut microbiota can affect the metabolic status of the body, in addition to having an important impact on blood pressure, blood glucose, and atherosclerosis, all of which are risk factors for ischemic stroke. In this review, we summarized studies that included the physiological function of the gut microbiota and gut microbiota disorders related to the central nervous system, thus providing novel ideas for the prevention and treatment of ischemic stroke.}, }
@article {pmid35417730, year = {2022}, author = {Wang, B and Liu, J and Lei, R and Xue, B and Li, Y and Tian, X and Zhang, K and Luo, B}, title = {Cold exposure, gut microbiota, and hypertension: A mechanistic study.}, journal = {The Science of the total environment}, volume = {833}, number = {}, pages = {155199}, doi = {10.1016/j.scitotenv.2022.155199}, pmid = {35417730}, issn = {1879-1026}, mesh = {Animals ; Bacteria/metabolism ; Butyrates ; Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome/physiology ; *Hypertension/etiology ; Male ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Cold exposure has been recognized as an important risk factor for hypertension, and altered gut microbiota has been reported to be associated with hypertension. We hypothesized that there is a plausible relationship between gut microbiota and cold-induced hypertension (CIH). Therefore, we explored the potential link between the gut microbiota and its metabolites with CIH. Male Sprague-Dawley (SD) rats were randomly divided into the normal temperature group (NT, 20 ± 2 °C) and the cold exposure group (CE, 4 ± 1 °C), and faecal bacteria cross-transplantation was performed after six weeks. We analyzed the gut microbiota of rats using the 16S rDNA sequence and measured the blood pressure of rats and the content of short-chain fatty acids in rat faeces. After six weeks of cold exposure, the CIH rat model was successfully established. The cold exposure reduced the diversity of the gut microbiota, increased the abundance of potentially pathogenic and conditionally pathogenic bacteria (e.g., Quinella, Rothia, and Senegalimassilia genera), and reduced the abundance of beneficial bacteria (e.g., Lactobacillus genus) and butyric acid-producing bacteria (e.g., Lachnospiraceae UCG-008 and Ruminococcaceae UCG-013 genera). Faecal bacteria cross-transplantation altered gut microbiota composition and regulated blood pressure levels. The NT group rats transplanted with CIH rats' faecal bacteria were enriched with certain conditional pathogenic bacteria such as Prevotellaceae UCG-003 genus. The CIH rats transplanted with faecal bacteria from the NT group rats were enriched with beneficial bacteria such as Bacteroides genus. In addition, we found a significant reduction in butyric acid levels in CIH rats, which may be related to the increase in blood pressure. In conclusion, CIH is associated with altered gut microbiota and reduced butyric acid. Our findings provide novel insights for the prevention and treatment of CIH by modulating the gut microbiota through supplementation of beneficial bacteria/butyrate.}, }
@article {pmid35416875, year = {2022}, author = {Cunha, FS and Jann, HW and Lugon, JR and Peralta, JM and Peralta, RHS}, title = {Molecular characterization of Cryptosporidium spp. obtained from fecal samples of immunosuppressed patients from Brazil.}, journal = {Revista da Sociedade Brasileira de Medicina Tropical}, volume = {55}, number = {}, pages = {e05552021}, pmid = {35416875}, issn = {1678-9849}, mesh = {Aged ; Brazil ; Child ; *Cryptosporidiosis/diagnosis ; *Cryptosporidium/genetics ; DNA, Protozoan/genetics ; Feces ; Genotype ; Humans ; Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Cryptosporidium spp. are pathogenic protozoans that play an important role in developing diseases in the elderly, children, and immunosuppressed individuals.<br><br>METHODS: The objective of this study was to detect and genetically characterize Cryptosporidium spp. in kidney transplanted patients (n = 97 samples; group 1) and immunosuppressed individuals from an outpatient clinic suspected of having Cryptosporidium infection (n = 53 samples; group 2). All fecal samples were analyzed by parasitological stool examination, immunochromatographic test, and real-time polymerase chain reaction (real-time PCR). Cryptosporidium-positive samples were tested using nested PCR for the gp60 gene, followed by sequencing for subtype determination.<br><br>RESULTS: Parasitological examination was negative in all Group 1, and positive in four Group 2 samples. Real-time PCR revealed Cryptosporidium in 13 samples: four in Group 1 (three C. hominis and one C. parvum) and nine in Group 2 (seven C. hominis, one C. parvum, and one mixed C. hominis/C. parvum). The immunochromatographic test was reactive in 11 samples (four in Group 1 and seven in Group 2). All 11 C. hominis isolates were identified as subtype IbA10G2 and one C. parvum as subtype IIbA15G2R1. All C. hominis belonged to subtype IbA10G2, which is recognized as the most prevalent and pathogenic subtype.<br><br>CONCLUSIONS: This study showed, for the first time, that the presence of Cryptosporidium subtypes is considered more virulent in Brazilian transplanted kidney patients.}, }
@article {pmid35411554, year = {2022}, author = {Botteri, E and Hoff, G and Randel, KR and Holme, &#xd8; and de Lange, T and Bernklev, T and Aas, E and Berthelsen, M and Natvig, E and Kirkøen, B and Knudsen, MD and Kvaerner, AS and Schult, AL and Ursin, G and Jørgensen, A and Berstad, P}, title = {Characteristics of nonparticipants in a randomised colorectal cancer screening trial comparing sigmoidoscopy and faecal immunochemical testing.}, journal = {International journal of cancer}, volume = {151}, number = {3}, pages = {361-371}, pmid = {35411554}, issn = {1097-0215}, mesh = {Colonoscopy ; *Colorectal Neoplasms/diagnosis/epidemiology/prevention &amp; control ; Early Detection of Cancer ; Humans ; Male ; Mass Screening ; Occult Blood ; *Sigmoidoscopy ; }, abstract = {Public health systems should guarantee universal access to health care services, including cancer screening. We assessed whether certain population subgroups were underrepresented among participants in colorectal cancer screening with sigmoidoscopy and faecal immunochemical testing (FIT). Between 2012 and 2019, about 140 000 individuals aged 50 to 74 years were randomly invited to once-only sigmoidoscopy or first round of FIT screening. Our study included 46 919 individuals invited to sigmoidoscopy and 70 019 to FIT between 2012 and 2017. We used logistic regression models to evaluate if demographic and socioeconomic factors and use of certain drugs were associated with participation. Twenty-four thousand one hundred and fifty-nine (51.5%) individuals attended sigmoidoscopy and 40 931 (58.5%) FIT screening. Male gender, young age, low education and income, being retired or unemployed, living alone, being an immigrant, long driving time to screening centre, and use of antidiabetic and psychotropic drugs were associated with low participation in both screening groups. Many of these factors also predicted low acceptance of colonoscopy after positive FIT. While male gender, young age and living alone were more strongly associated with nonparticipation in FIT than sigmoidoscopy, low education and income, being retired or immigrant and long driving time were more strongly associated with nonparticipation in sigmoidoscopy than FIT. In conclusion, participation was lower in sigmoidoscopy than FIT. Predictors of nonparticipation were similar between arms. However, low socioeconomic status, being an immigrant and long driving time affected participation more in sigmoidoscopy screening, suggesting that FIT may guarantee more equal access to screening services than sigmoidoscopy.}, }
@article {pmid35409202, year = {2022}, author = {Bastos, RMC and Simplício-Filho, A and Sávio-Silva, C and Oliveira, LFV and Cruz, GNF and Sousa, EH and Noronha, IL and Mangueira, CLP and Quaglierini-Ribeiro, H and Josefi-Rocha, GR and Rangel, &#xc9;B}, title = {Fecal Microbiota Transplant in a Pre-Clinical Model of Type 2 Diabetes Mellitus, Obesity and Diabetic Kidney Disease.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409202}, issn = {1422-0067}, support = {2013/19560-6; 2017/23195-2; 2017/18072-9; 2016/26263-6//S&#xe3;o Paulo Research Foundation/ ; 2016-5/423320//National Council for Scientific and Technological Development/ ; 2015//European Foundation for the Study of Diabetes/Sanofi/ ; }, mesh = {Albuminuria/complications ; Animals ; *Diabetes Mellitus, Type 2/complications/metabolism/therapy ; *Diabetic Nephropathies/metabolism ; Fecal Microbiota Transplantation/adverse effects ; Mice ; Mice, Inbred Strains ; Obesity/complications/metabolism/therapy ; }, abstract = {Diabetes mellitus (DM) burden encompasses diabetic kidney disease (DKD), the leading cause of end-stage renal disease worldwide. Despite compelling evidence indicating that pharmacological intervention curtails DKD progression, the search for non-pharmacological strategies can identify novel targets for drug development against metabolic diseases. One of those emergent strategies comprises the modulation of the intestinal microbiota through fecal transplant from healthy donors. This study sought to investigate the benefits of fecal microbiota transplant (FMT) on functional and morphological parameters in a preclinical model of type 2 DM, obesity, and DKD using BTBR[ob/ob] mice. These animals develop hyperglycemia and albuminuria in a time-dependent manner, mimicking DKD in humans. Our main findings unveiled that FMT prevented body weight gain, reduced albuminuria and tumor necrosis factor-α (TNF-α) levels within the ileum and ascending colon, and potentially ameliorated insulin resistance in BTBR[ob/ob] mice. Intestinal structural integrity was maintained. Notably, FMT was associated with the abundance of the succinate-consuming Odoribacteraceae bacteria family throughout the intestine. Collectively, our data pointed out the safety and efficacy of FMT in a preclinical model of type 2 DM, obesity, and DKD. These findings provide a basis for translational research on intestinal microbiota modulation and testing its therapeutic potential combined with current treatment for DM.}, }
@article {pmid35409083, year = {2022}, author = {Wu, R and Shen, Q and Li, P and Shang, N}, title = {Sturgeon Chondroitin Sulfate Restores the Balance of Gut Microbiota in Colorectal Cancer Bearing Mice.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409083}, issn = {1422-0067}, mesh = {Amino Acids/metabolism ; Animals ; Chondroitin Sulfates/chemistry ; *Colorectal Neoplasms/pathology ; Feces/chemistry ; Fishes/metabolism ; *Gastrointestinal Microbiome ; Metabolome ; Mice ; }, abstract = {Chondroitin sulfate (CS) is a well-known bioactive substance with multiple biological functions, which can be extracted from animal cartilage or bone. Sturgeon, the largest soft bone animal with ~20% cartilage content, is a great candidate for CS production. Our recent study confirmed the role of sturgeon chondroitin sulfate (SCS) in reducing colorectal cancer cell proliferation and tumor formation. Here, we further studied the effect of SCS on modulating gut microbiome structure in colorectal cancer bearing mice. In this study, the transplanted tumor mice model was constructed to demonstrate that SCS can effectively halt the growth of transplanted colorectal tumor cells. Next, we showed that SCS significantly altered the gut microbiome, such as the abundance of Lactobacillales, Gastranaerophilales, Ruminiclostridiun_5 and Ruminiclostridiun_6. According to linear discriminant analysis (LDA) and abundance map analysis of the microbial metabolic pathways, the changes in microbial abundance led to an increase of certain metabolites (e.g., Phe, Tyr, and Gly). Fecal metabolome results demonstrated that SCS can significantly reduce the amount of certain amino acids such as Phe, Pro, Ala, Tyr and Leu presented in the feces, suggesting that SCS might inhibit colorectal cancer growth by modulating the gut microbiome and altering the production of certain amino acids. Our results revealed the therapeutic potential of SCS to facilitate treatment of colorectal cancer. This study provides insights into the development of novel food-derived therapies for colorectal cancer.}, }
@article {pmid35402293, year = {2022}, author = {Ding, D and Yong, H and You, N and Lu, W and Yang, X and Ye, X and Wang, Y and Cai, T and Zheng, X and Chen, H and Cui, B and Zhang, F and Liu, X and Mao, JH and Lu, Y and Chang, H}, title = {Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {820367}, pmid = {35402293}, issn = {2235-2988}, mesh = {*Diabetes Mellitus, Type 2/therapy ; *Fecal Microbiota Transplantation ; Feces ; Glycated Hemoglobin ; Humans ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {BACKGROUND: Increasing evidence shows that alterations in gut microbiome (GM) contribute to the development of type 2 diabetes mellitus (T2DM), and fecal microbiota transplantation (FMT) successfully treats various human diseases. However, the benefits of FMT therapy to T2DM patients remain unknown.<br><br>METHODS: We enrolled 17 patients with T2DM for nonblinded, one-armed intervention trial of FMT. A total of 20 healthy individuals were recruited as the baseline control. HbA1c% and metabolic parameter change were evaluated in 17 T2DM patients 12 weeks after they received FMT from healthy donors. The GM composition was characterized by 16S rRNA gene amplicon sequencing from fecal samples prior to and 12 weeks after FMT treatment.<br><br>RESULTS: We found that the GM of T2DM patients was reconstituted by FMT. We observed a statistically significant decrease in HbA1c% (from 7.565 &#xb1; 0.148 to 7.190 &#xb1; 0.210, p<0.01), blood glucose (from 8.483 &#xb1; 0.497 to 7.286 &#xb1; 0.454 mmol/L, p<0.01), and uric acid (from 309.4 &#xb1; 21.5 to 259.1 &#xb1; 15.8 &#xb5;mol/L, p<0.01) while a significant increase in postprandial C-peptide (from 4.503 &#xb1; 0.600 to 5.471 &#xb1; 0.728 ng/ml, p<0.01) at 12 weeks after FMT. Closely evaluating the changes in these assays, we found individual variability in response to FMT treatment. Out of 17 T2DM patients, 11 were found to significantly improve T2DM symptoms. The FMT responders have significantly higher levels of the family Rikenellaceae and the genus Anaerotruncus (family Ruminococcaceae) in their pretreated fecal in comparison to nonresponders, which could predict the clinical response with an area under the curve of 0.83.<br><br>CONCLUSION: Our findings suggest that certain T2DM patients can potentially benefit from FMT, and the pretreated abundance of Rikenellaceae and Anaerotruncus in the fecal of patients may serve as potential biomarkers for selecting T2DM patients to receive FMT.}, }
@article {pmid35401492, year = {2022}, author = {Gao, JM and Rao, JH and Wei, ZY and Xia, SY and Huang, L and Tang, MT and Hide, G and Zheng, TT and Li, JH and Zhao, GA and Sun, YX and Chen, JH}, title = {Transplantation of Gut Microbiota From High-Fat-Diet-Tolerant Cynomolgus Monkeys Alleviates Hyperlipidemia and Hepatic Steatosis in Rats.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {876043}, pmid = {35401492}, issn = {1664-302X}, abstract = {Emerging evidence has been reported to support the involvement of the gut microbiota in the host's blood lipid and hyperlipidemia (HLP). However, there remains unexplained variation in the host's blood lipid phenotype. Herein a nonhuman primate HLP model was established in cynomolgus monkeys fed a high-fat diet (HFD) for 19 months. At month 19%, 60% (3/5) of the HFD monkeys developed HLP, but surprisingly 40% of them (2/5) exhibited strong tolerance to the HFD (HFD-T) with their blood lipid profiles returning to normal levels. Metagenomic analysis was used to investigate the compositional changes in the gut microbiota in these monkeys. Furthermore, the relative abundance of Megasphaera remarkably increased and became the dominant gut microbe in HFD-T monkeys. A validation experiment showed that transplantation of fecal microbiota from HFD-T monkeys reduced the blood lipid levels and hepatic steatosis in HLP rats. Furthermore, the relative abundance of Megasphaera significantly increased in rats receiving transplantation, confirming the successful colonization of the microbe in the host and its correlation with the change of the host's blood lipid profiles. Our results thus suggested a potentially pivotal lipid-lowering role of Megasphaera in the gut microbiota, which could contribute to the variation in the host's blood lipid phenotype.}, }
@article {pmid35400819, year = {2022}, author = {Fukushima, S and Shiotani, A and Matsumoto, H and Handa, O and Handa, Y and Osawa, M and Murao, T and Umegaki, E and Kawano, M and Inoue, R and Naito, Y}, title = {Comparison of mucosa-associated microbiota in Crohn's disease patients with and without anti-tumor necrosis factor-α therapy.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {70}, number = {2}, pages = {182-188}, pmid = {35400819}, issn = {0912-0009}, abstract = {Most studies on the gut microbiome of Crohn's disease have been conducted using feces, instead of intestinal mucus to analyze the mucosa-associated microbiota. To investigate the characteristics of mucosa-associated microbiota in Crohn's disease patients and the effect of anti-tumor necrosis factor (TNF)-α therapy on mucosa-associated microbiota, we analyzed microbiota in Crohn's disease patients using brushing samples taken from terminal ileum. The recruited subjects were 18 Crohn's disease patients and 13 controls. There were 10 patients with anti-TNF-α therapy in Crohn's disease group. Crohn's disease patients had significantly reduced α-diversity in Shannon index compared to the controls. The comparative analysis of the taxonomic composition at the genus level between the Crohn's disease group and the controls indicated that butyrate-producing bacteria were less abundant in the Crohn's disease group compared to the controls. There were no differences in the diversity between the patients taking anti-TNF-α therapy and the patients without. The comparative analysis of the taxonomic composition at the genus level between the two groups indicated that some of anti-inflammatory bacteria were less abundant in the anti-TNF-α therapy group than the other. Reduction of specific bacteria producing anti-inflammatory molecules, especially butyrate-producing bacteria may play important roles in the pathophysiology of Crohn's disease.}, }
@article {pmid35399688, year = {2022}, author = {He, Z and Ma, Y and Chen, X and Liu, S and Xiao, J and Wang, Y and Wang, W and Yang, H and Li, S and Cao, Z}, title = {Protective Effects of Intestinal Gallic Acid in Neonatal Dairy Calves Against Extended-Spectrum β-lactamase Producing Enteroaggregative Escherichia coli Infection: Modulating Intestinal Homeostasis and Colitis.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {864080}, pmid = {35399688}, issn = {2296-861X}, abstract = {Calf diarrhea induced by enteroaggregative E. coli (EAEC) spreads fast among young ruminants, causing continuous hazard to dairy industry. Antimicrobial drug abuse aggravates the incidence rate of multi-drug resistant (MDR) extended-spectrum β-lactamase-producing E. coli (ESBL-EC). However, knowledge of detection and significance of disease-related biomarkers in neonatal female calves are still limited. Gallic acid (GA), a natural secondary metabolite mostly derived from plants, has attracted increasing attention for its excellent anti-inflammatory and anti-oxidative properties. However, it is vague how GA engenders amelioration effects on clinical symptoms and colitis induced by ESBL-EAEC infection in neonatal animals. Here, differentiated gut microbiome and fecal metabolome discerned from neonatal calves were analyzed to ascertain biomarkers in their early lives. Commensal Collinsella and Coriobacterium acted as key microbial markers mediating colonization resistance. In addition, there exists a strongly positive relation between GA, short-chain fatty acid (SCFA) or other prebiotics, and those commensals using random forest machine learning algorithm and Spearman correlation analyses. The protective effect of GA pretreatment on bacterial growth, cell adherence, and ESBL-EAEC-lipopolysaccharide (LPS)-treated Caco-2 cells were first assessed, and results revealed direct antibacterial effects and diminished colonic cell inflammation. Then, oral GA mediated colitis attenuation and recovery of colonic short-chain fatty acid (SCFA) productions on neonatal mice peritonitis sepsis or oral infection model. To corroborate this phenomenon, fecal microbiota transplantation (FMT) method was adopted to remedy the bacterial infection. Of note, FMT from GA-treated neonatal mice achieved profound remission of clinical symptoms and colitis over the other groups as demonstrated by antibacterial capability and prominent anti-inflammatory abilities, revealing improved hindgut microbiota structure with enriched Clostridia_UCG-014, Lachnospiraceae, Oscillospiraceae, and Enterococcaceae, and upregulation of SCFA productions. Collectively, our findings provided the direct evidence of hindgut microbiota and intestinal metabolites, discriminating the health status of neonatal calves post ESBL-EAEC infection. The data provided novel insights into GA-mediated remission of colitis via amelioration of hindgut commensal structure and upregulation of SCFA productions. In addition, its eminent role as potential antibiotic alternative or synergist for future clinic ESBL-EAEC control in livestock.}, }
@article {pmid35399089, year = {2022}, author = {Wang, X and Tsai, T and Zuo, B and Wei, X and Deng, F and Li, Y and Maxwell, CV and Yang, H and Xiao, Y and Zhao, J}, title = {Donor age and body weight determine the effects of fecal microbiota transplantation on growth performance, and fecal microbiota development in recipient pigs.}, journal = {Journal of animal science and biotechnology}, volume = {13}, number = {1}, pages = {49}, pmid = {35399089}, issn = {1674-9782}, support = {2018-67015-27479//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: The application of fecal microbiota transplantation (FMT) to improve swine growth performance has been sporadically studied. Most of these studies used a single microbiota source and thus the effect of donor characteristics on recipient pigs' fecal microbiota development and growth performance is largely unknown.<br><br>RESULTS: In this study, we collected feces from six donors with heavy (H) or light (L) body weight and different ages (d 42, nursery; d 96, growing; and d 170, finisher) to evaluate their effects on the growth performance and fecal microbiota development of recipient pigs. Generally, recipients that received two doses of FMT from nursery and finisher stages donor at weaning (21&#x2009;&#xb1;&#x2009;2&#x2009;days of age) inherited the donor's growth pattern, while the pigs gavaged with grower stage material exerted a numerically greater weight gain than the control pigs regardless of donor BW. FMT from heavier donors (NH, GH, and FH) led to the recipients to have numerically increased growth compared to their lighter counterparts (NL, GL, and FL, respectively) throughout the growing and most finishing stages. This benefit could be attributed to the enrichment of ASV25 Faecalibacterium, ASV61 Faecalibacterium, ASV438 Coriobacteriaceae_unclassified, ASV144 Bulleidia, and ASV129 Oribacterium and decrease of ASV13 Escherichia during nursery stage. Fecal microbiota transplantation from growing and finishing donors influenced the microbial community significantly in recipient pigs during the nursery stage. FMT of older donors' gut microbiota expedited recipients' microbiota maturity on d 35 and 49, indicated by increased estimated microbiota ages. The age-associated bacterial taxa included ASV206 Ruminococcaceae, ASV211 Butyrivibrio, ASV416 Bacteroides, ASV2 Streptococcus, and ASV291 Veillonellaceae. The body weight differences between GL and GH pigs on d 104 were associated with the increased synthesis of the essential amino acid, lysine and methionine, mixed acid fermentation, expedited glycolysis, and sucrose/galactose degradation.<br><br>CONCLUSIONS: Overall, our study provided insights into how donor age and body weight affect FMT outcomes regarding growth performance, microbiota community shifts, and lower GI tract metabolic potentials. This study also provided guidance to select qualified donors for future fecal microbiota transplantation.}, }
@article {pmid35398532, year = {2022}, author = {Johnson, S and Gerding, DN and Li, X and Reda, DJ and Donskey, CJ and Gupta, K and Goetz, MB and Climo, MW and Gordin, FM and Ringer, R and Johnson, N and Johnson, M and Calais, LA and Goldberg, AM and Ge, L and Haegerich, T}, title = {Defining optimal treatment for recurrent Clostridioides difficile infection (OpTION study): A randomized, double-blind comparison of three antibiotic regimens for patients with a first or second recurrence.}, journal = {Contemporary clinical trials}, volume = {116}, number = {}, pages = {106756}, doi = {10.1016/j.cct.2022.106756}, pmid = {35398532}, issn = {1559-2030}, mesh = {Anti-Bacterial Agents ; *COVID-19 ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/drug therapy ; Diarrhea/chemically induced/drug therapy ; Fidaxomicin/therapeutic use ; Humans ; Recurrence ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Although many large, randomized controlled trials (RCT) have been conducted on antibiotic therapy for patients with primary C. difficile infections (CDI), few RCTs have been performed for patients with recurrent CDI (rCDI). In addition, fecal microbial transplant (FMT) is neither FDA-approved or guideline-recommended for patients with pauci-rCDI (first or second recurrences). Therefore, a rigorous RCT of sufficient size was designed to determine the optimal treatment among three antibiotic regimens in current practice for treatment of pauci-rCDI.<br><br>METHODS: VA Cooperative Studies Program (CSP) #596 is a prospective, double-blind, multi-center clinical trial of veteran patients with pauci-rCDI comparing fidaxomicin (FDX) 200&#xa0;mg twice daily for 10&#xa0;days and vancomycin (VAN) 125&#xa0;mg four times daily for 10&#xa0;days followed by a 3-week vancomycin taper and pulse (VAN-T/P) regimen to a standard course of VAN 125&#xa0;mg four times daily for 10&#xa0;days. The primary endpoint is sustained clinical response at day 59, with sustained response measured as a diarrhea composite outcome (D-COM) that includes symptom resolution during treatment (before day 10) without recurrence of diarrhea or other clinically important outcomes through day 59.<br><br>DISCUSSION: CSP study 596 is designed to compare three current antibiotic treatments for recurrent CDI that are in clinical practice, but which lack high-quality evidence to support strong guideline recommendations. The design of the study which included a pilot phase initiated at six sites with expansion to 24 sites is described along with protocol modifications based on early trial experience and clinical realities including the COVID-19 pandemic.<br><br>TRIAL REGISTRATION: This study is registered with clinicaltrials.gov (Identifier: NCT02667418).}, }
@article {pmid35398345, year = {2022}, author = {Osman, M and Budree, S and Kelly, CR and Panchal, P and Allegretti, JR and Kassam, Z and , }, title = {Effectiveness and Safety of Fecal Microbiota Transplantation for Clostridioides Difficile Infection: Results From a 5344-Patient Cohort Study.}, journal = {Gastroenterology}, volume = {163}, number = {1}, pages = {319-322}, doi = {10.1053/j.gastro.2022.03.051}, pmid = {35398345}, issn = {1528-0012}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Cohort Studies ; Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; Recurrence ; Treatment Outcome ; }, }
@article {pmid35396768, year = {2022}, author = {Ma, C and Azad, MAK and Tang, W and Zhu, Q and Wang, W and Gao, Q and Kong, X}, title = {Maternal probiotics supplementation improves immune and antioxidant function in suckling piglets via modifying gut microbiota.}, journal = {Journal of applied microbiology}, volume = {133}, number = {2}, pages = {515-528}, doi = {10.1111/jam.15572}, pmid = {35396768}, issn = {1365-2672}, support = {31772613//National Natural Science Foundation of China/ ; 2019RS3022//Special Funds for Construction of Innovative Provinces in Hunan Province/ ; //Industry and Research Talent Support Project from Wang Kuancheng of the Chinese Academy of Sciences/ ; }, mesh = {Animal Feed/analysis ; Animals ; Animals, Suckling ; Antioxidants/pharmacology ; Diet/veterinary ; Dietary Supplements/analysis ; Female ; *Gastrointestinal Microbiome ; Lactation ; Pregnancy ; *Probiotics/analysis ; Swine ; Swine, Miniature ; }, abstract = {AIM: Probiotics could improve the health, growth, and development of host or their foetuses/offspring via regulating gut microbiota. The present study was conducted to determine the effects of maternal probiotics supplementation on gut microbiota and metabolites of sows and their suckling piglets, as well as plasma biochemical parameters, oxidative/anti-oxidative indexes, and inflammatory cytokine levels of suckling piglets.<br><br>METHODS AND RESULTS: A total of 32 pregnant Bama mini-pigs were selected and randomly divided into two groups. The sows were fed a basal diet (control group) or a basal diet supplemented with probiotics (probiotics group) from mating to day 21 of lactation. Samples from sows were collected on day 105 of pregnancy and day 21 of lactation and from piglets on day 21 of lactation. The results showed that probiotics supplementation increased the faecal abundances of Ruminococcus, Bacteroides, and Anaeroplasma and decreased Tenericutes on day 105 of pregnancy while increased the abundances of Actinobacteria and Anaerostipes and decreased Proteobacteria and Desulfovibrio on day 21 of lactation. In addition, probiotics supplementation decreased the faecal levels of tryptamine, putrescine, and cadaverine on day 105 of pregnancy and isovalerate and skatole on day 21 of lactation while increased butyrate level on day 21 of lactation. Further studies showed that maternal probiotics supplementation decreased the plasma levels of AMM, TC, LDL-C, Ala, Tau, MDA, H2 O2 , IL-1&#x3b2;, IL-2, IL-6, and IFN-&#x3b1; of suckling piglets. Moreover, maternal probiotics supplementation increased the abundances of Deferribacteres, Fusobacteria, and Fusobacterium while decreased Anaerostipes in piglet's colon. Spearman's correlation analysis revealed a potential link between gut microbiota alterations and their metabolites.<br><br>CONCLUSIONS: Dietary probiotics supplementation during pregnancy and lactation periods could improve sow status, alleviate oxidative stress and inflammation response, and improve nutrient metabolism of piglets by altering the gut microbiota.<br><br>The probiotics alter maternal and offspring's gut microbiota involving in offspring's physiological and metabolic changes, and present a new perspective that the effects of gut microbiota changes induced by probiotics supplementation will help in addressing the growth and development and health problem of their foetuses/offspring.}, }
@article {pmid35393390, year = {2022}, author = {Segovia-Rodríguez, L and Echeverry-Alzate, V and Rincón-Pérez, I and Calleja-Conde, J and Bühler, KM and Giné, E and Albert, J and Hinojosa, JA and Huertas, E and Gómez-Gallego, F and Bressa, C and Rodríguez de Fonseca, F and López-Moreno, JA}, title = {Gut microbiota and voluntary alcohol consumption.}, journal = {Translational psychiatry}, volume = {12}, number = {1}, pages = {146}, pmid = {35393390}, issn = {2158-3188}, mesh = {Alcohol Drinking ; Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Male ; Rats ; Rats, Wistar ; }, abstract = {Alcohol is part of the usual diet of millions of individuals worldwide. However, not all individuals who drink alcohol experience the same effects, nor will everyone develop an alcohol use disorder. Here we propose that the intestinal microbiota (IMB) helps explain the different consumption patterns of alcohol among individuals. 507 humans participated in this study and alcohol consumption and IMB composition were analyzed. On the other hand, in 80 adult male Wistar rats, behavioral tests, alcohol intoxication, fecal transplantation, administration of antibiotics and collection of fecal samples were performed. For identification and relative quantification of bacterial taxa was used the bacterial 16 S ribosomal RNA gene. In humans, we found that heavy episodic drinking is associated with a specific stool type phenotype (type 1, according to Bristol Stool Scale; p < 0.05) and with an increase in the abundance of Actinobacteria (p < 0.05). Next, using rats, we demonstrate that the transfer of IMB from alcohol-intoxicated animals causes an increase in voluntary alcohol consumption in transplant-recipient animals (p < 0.001). The relative quantification data indicate that the genus Porphyromonas could be associated with the effect on voluntary alcohol consumption. We also show that gut microbiota depletion by antibiotics administration causes a reduction in alcohol consumption (p < 0.001) and altered the relative abundance of relevant phyla such as Firmicutes, Bacteroidetes or Cyanobacteria (p < 0.05), among others. Benjamini-Hochberg false discovery rate (FDR) correction was performed for multiple comparisons. These studies reveal some of the consequences of alcohol on the IMB and provide evidence that manipulation of IMB may alter voluntary alcohol consumption.}, }
@article {pmid35390687, year = {2022}, author = {Huang, C and Wu, D and Zhang, K and Khan, FA and Pandupuspitasari, NS and Wang, Y and Huo, L and Sun, F}, title = {Perfluorooctanoic acid alters the developmental trajectory of female germ cells and embryos in rodents and its potential mechanism.}, journal = {Ecotoxicology and environmental safety}, volume = {236}, number = {}, pages = {113467}, doi = {10.1016/j.ecoenv.2022.113467}, pmid = {35390687}, issn = {1090-2414}, mesh = {Animals ; Caprylates/toxicity ; Female ; Fetal Growth Retardation ; *Fluorocarbons/toxicity ; Germ Cells ; Humans ; *Melatonin ; *Metformin ; Rodentia ; Serine ; }, abstract = {The epidemiological studies regarding perfluorooctanoic acid (PFOA) suggests that its exposure causes reproductive health issues, the underlying mechanisms of which are still in its infancy. Here, we report that PFOA deteriorates female reproduction at multiple development stages. Oocyte meiosis and preimplantation development are severely impaired by PFOA with oxidative stress being a contributor. Supplementing with antioxidant melatonin partially rescues oocyte meiotic maturation and non-apoptotic demise. The attenuation in ovarian follicle development however can be improved by metformin but not melatonin. Importantly, metformin blunts PFOA-induced fetal growth retardation (FGR) and such protective effect could be recapitulated by transplantation of fecal material and pharmacological activation of AMPK. Mechanistically, PFOA causes gut microbiota dysbiosis, which might thereby rewire host metabolism of L-phenylalanine, histamine and L-palmitoylcarnitine that triggers hyperphenylalaninaemia, inflammation and ferroptosis to initiate FGR. Deregulated serine metabolism by the gut microbe constitutes an alternative mechanism underlying PFOA-induced FGR in that modulation of serine in dam's diet phenocopied the FGR. Our study expands the understanding of risk factors that impair human reproductive health, and proposes restoration of gut microbiota diversity and intervention of metabolism as therapeutics mitigating health risks predisposed by environmental perturbation.}, }
@article {pmid35389754, year = {2023}, author = {Gu, Y and Li, L and Yang, M and Liu, T and Song, X and Qin, X and Xu, X and Liu, J and Wang, B and Cao, H}, title = {Bile acid-gut microbiota crosstalk in irritable bowel syndrome.}, journal = {Critical reviews in microbiology}, volume = {49}, number = {3}, pages = {350-369}, doi = {10.1080/1040841X.2022.2058353}, pmid = {35389754}, issn = {1549-7828}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Irritable Bowel Syndrome/drug therapy ; Bile Acids and Salts/therapeutic use ; *Probiotics ; Diarrhea ; }, abstract = {Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with an increasing prevalence, and its precise aetiology remains unclear. Gut microbiota dysbiosis has been found to be associated with IBS pathogenesis. In addition, a high incidence of bile acid diarrhoea and disturbed bile acid metabolism has been observed in IBS patients. The abundant microorganisms inhabited in human gut have essential functions in bile acid biotransformation, and can immensely affect the size and constitution of bile acid pool. Meanwhile, the alterations of bile acid profile can inversely interfere with the gut microbiota. This review discussed the role of intricate correlations between bile acids and gut microbiota in IBS pathogenesis and delineated the possible molecular mechanisms, mainly the signalling induced by farnesoid X receptor and transmembrane G protein-coupled receptor 5. Besides, some biomarkers for identifying bile acid diarrhoea in IBS population were listed, assisting the diagnosis and classification of IBS. Moreover, it also assessed some therapeutic strategies for IBS that regulate the bile acid-gut microbiota axis, such as dietary modulation, probiotics/prebiotics, faecal microbiota transplantation, and antibiotics. Collectively, this article illustrated the relationship between bile acids and gut microbiota in IBS pathophysiology and might offer some novel therapeutic options for IBS.}, }
@article {pmid35388189, year = {2022}, author = {Aggarwala, V and Mogno, I and Li, Z and Yang, C and Britton, GJ and Chen-Liaw, A and Mitcham, J and Bongers, G and Gevers, D and Clemente, JC and Colombel, JF and Grinspan, A and Faith, J}, title = {Author Correction: Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes.}, journal = {Nature microbiology}, volume = {7}, number = {5}, pages = {736}, doi = {10.1038/s41564-022-01118-8}, pmid = {35388189}, issn = {2058-5276}, support = {650451//Crohn's and Colitis Foundation (Crohn's &amp; Colitis Foundation)/ ; 580924//Crohn's and Colitis Foundation (Crohn's &amp; Colitis Foundation)/ ; }, }
@article {pmid35387936, year = {2022}, author = {Tamura, S and Ishida, H and Shimizu, T and Imaeda, H and Nishida, A and Bamba, S and Andoh, A and Iwasa, Y and Kuroda, H}, title = {[Fecal microbiota transplantation for refractory Clostridioides difficile infection with Crohn's disease in an allogeneic bone marrow transplant recipient].}, journal = {[Rinsho ketsueki] The Japanese journal of clinical hematology}, volume = {63}, number = {3}, pages = {217-223}, doi = {10.11406/rinketsu.63.217}, pmid = {35387936}, issn = {0485-1439}, mesh = {Adolescent ; Bone Marrow ; Bone Marrow Transplantation ; *Clostridioides difficile ; *Clostridium Infections/therapy ; *Crohn Disease ; Fecal Microbiota Transplantation/methods ; Female ; *Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation ; Humans ; Recurrence ; Transplant Recipients ; Treatment Outcome ; }, abstract = {We report a case of a 15-year-old girl who developed refractory Clostridioides difficile infection (CDI) after allogeneic bone marrow transplantation (BMT). She was treated successfully with fecal microbiota transplantation (FMT). The patient who had aplastic anemia underwent allogeneic BMT from an HLA 1-locus-mismatched unrelated donor. Four months later, she developed gastrointestinal graft-versus-host disease (GVHD), and immunosuppressive treatment improved the GVHD. However, she developed CDI 5 months after BMT and experienced recurrence after that. Fifteen months after transplant, CDI relapsed despite discontinuation of immunosuppressive treatment; thus, she underwent FMT. Colonoscopy at the time of FMT revealed round aphthae, mainly in the ileocecum, and colonic biopsy revealed inflammatory cell infiltration and noncaseating epithelioid granuloma, which fulfilled the diagnostic criteria for Crohn's disease. Following FMT for CDI, she was treated with enteric budesonide and intravenous methotrexate for Crohn's disease. These interventions resulted in a marked improvement in both CDI and Crohn's disease. Twenty-eight months after FMT, both CDI and Crohn's disease remained in remission with oral mesalamine monotherapy.}, }
@article {pmid35387830, year = {2022}, author = {Pérez-Nadales, E and Cano, &#xc1; and Recio, M and Artacho, MJ and Guzmán-Puche, J and Doblas, A and Vidal, E and Natera, C and Martínez-Martínez, L and Torre-Cisneros, J and Castón, JJ}, title = {Randomised, double-blind, placebo-controlled, phase 2, superiority trial to demonstrate the effectiveness of faecal microbiota transplantation for selective intestinal decolonisation of patients colonised by carbapenemase-producing Klebsiella pneumoniae (KAPEDIS).}, journal = {BMJ open}, volume = {12}, number = {4}, pages = {e058124}, pmid = {35387830}, issn = {2044-6055}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Proteins ; *Carbapenem-Resistant Enterobacteriaceae ; Fecal Microbiota Transplantation/methods ; Humans ; *Klebsiella Infections/drug therapy ; Klebsiella pneumoniae ; beta-Lactamases ; }, abstract = {INTRODUCTION: Infections caused by carbapenemase-producing Enterobacterales are frequent and associated with high rates of mortality. Intestinal carriers are at increased risk of infection by these microorganisms. Decolonisation strategies with antibiotics have not obtained conclusive results. Faecal microbiota transplantation (FMT) could be an effective and safe strategy to decolonise intestinal carriers of KPC-producing Klebsiella pneumoniae (KPC-Kp) but this hypothesis needs evaluation in appropriate clinical trials.<br><br>METHODS AND ANALYSIS: The KAPEDIS trial is a single-centre, randomised, double-blind, placebo-controlled, phase 2, superiority clinical trial of FMT for eradication of intestinal colonisation by KPC-Kp. One hundred and twenty patients with rectal colonisation by KPC-Kp will be randomised 1:1 to receive encapsulated lyophilised FMT or placebo. The primary outcome is KPC-Kp eradication at 30 days. Secondary outcomes are: (1) frequency of adverse events; (2) changes in KPC-Kp relative load within the intestinal microbiota at 7, 30 and 90 days, estimated by real-time quantitative PCR analysis of rectal swab samples and (3) rates of persistent eradication, KPC-Kp infection and crude mortality at 90 days. Participants will be monitored for adverse effects throughout the intervention.<br><br>ETHICS AND DISSEMINATION: Ethical approval was obtained from Reina Sof&#xed;a University Hospital Institutional Review Board (approval reference number: 2019-003808-13). Trial results will be published in peer-reviewed journals and disseminated at national and international conferences.<br><br>TRIAL REGISTRATION NUMBER: NCT04760665.}, }
@article {pmid35386224, year = {2022}, author = {Zhang, H and Xu, J and Wu, Q and Fang, H and Shao, X and Ouyang, X and He, Z and Deng, Y and Chen, C}, title = {Gut Microbiota Mediates the Susceptibility of Mice to Sepsis-Associated Encephalopathy by Butyric Acid.}, journal = {Journal of inflammation research}, volume = {15}, number = {}, pages = {2103-2119}, pmid = {35386224}, issn = {1178-7031}, abstract = {PURPOSE: Neuroinflammation plays an important part in the pathophysiology of sepsis-associated encephalopathy (SAE). Gut microbiota and gut brain axis are considered as important mediators in the development of neurological diseases. The aim of this study was to investigate the role of intestinal microbiota in sepsis-related brain injury and to explore the underlying mechanisms.<br><br>METHODS: Mouse model of SAE was established using cecal ligation and puncture (CLP). Based on the mouse mortality and the associated time of death, light SAE (LSAE) and severe SAE (SSAE) were classified. Fecal microbiota transplantation (FMT) was performed to verify the role of intestinal microbiota. Feces of mice in the two groups which collected before operation were sequenced for 16S and targeted short chain fatty acids.<br><br>RESULTS: Intestinal microbiota from SSAE and LSAE mice displayed diverse functions. Interestingly, LSAE mice produced more butyric acid compared with SSAE mice. In the in vivo experiments, sodium butyrate (NaB) reduced the high oxidative stress levels in mice hippocampus and conferred a marked survival superiority to sepsis mice. In addition, NaB prevented the increase in intracellular reactive oxygen species (ROS) generation and inducible nitric-oxide synthase expression in LPS-stimulated primary microglia. The GPR109A/Nrf2/HO-1 signaling pathway was found to be involved in the activation of antioxidant response of primary microglia induced by sodium butyrate.<br><br>CONCLUSION: Our findings indicate a crucial role of gut microbiota in the susceptibility to SAE. Butyrate, a metabolite of intestinal microbiota, may have a neuroprotective effect in the process of sepsis by GPR109A/Nrf2/HO-1 pathway.}, }
@article {pmid35384688, year = {2022}, author = {Cruz, N and Abernathy, GA and Dichosa, AEK and Kumar, A}, title = {The Age of Next-Generation Therapeutic-Microbe Discovery: Exploiting Microbe-Microbe and Host-Microbe Interactions for Disease Prevention.}, journal = {Infection and immunity}, volume = {90}, number = {5}, pages = {e0058921}, pmid = {35384688}, issn = {1098-5522}, mesh = {Feces ; Host Microbial Interactions ; Humans ; Microbial Interactions ; *Microbiota ; *Probiotics ; }, abstract = {Humans are considered "superorganisms," harboring a diverse microbial collective that outnumbers human cells 10 to 1. Complex and gravely understudied host- and microbe-microbe interactions-the product of millions of years of host-microbe coevolution-govern the superorganism in almost every aspect of life functions and overall well-being. Abruptly disrupting these interactions via extrinsic factors has undesirable consequences for the host. On the other hand, supplementing commensal or beneficial microbes may mitigate perturbed interactions or enhance the interactive relationships that ultimately benefit all parties. Hence, immense efforts have focused on dissecting the innumerable host- and microbe-microbe relationships to characterize if a "positive" or "negative" interaction is at play and to exploit such behavior for broader implications. For example, microbiome research has worked to identify and isolate naturally antipathogenic microbes that may offer therapeutic potential either in a direct, one-on-one application or by leveraging its unique metabolic properties. However, the discovery and isolation of such desired therapeutic microbes from complex microbiota have proven challenging. Currently, there is no conventional technique to universally and functionally screen for these microbes. With this said, we first describe in this review the historical (probiotics) and current (fecal microbiota or defined consortia) perspectives on therapeutic microbes, present the discoveries of therapeutic microbes through exploiting microbe-microbe and host-microbe interactions, and detail our team's efforts in discovering therapeutic microbes via our novel microbiome screening platform. We conclude this minireview by briefly discussing challenges and possible solutions with therapeutic microbes' applications and paths ahead for discovery.}, }
@article {pmid35384391, year = {2022}, author = {Bloom, PP and Donlan, J and Torres Soto, M and Daidone, M and Hohmann, E and Chung, RT}, title = {Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient.}, journal = {Hepatology communications}, volume = {6}, number = {8}, pages = {2079-2089}, pmid = {35384391}, issn = {2471-254X}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Capsules ; *Cognition/physiology ; *Fecal Microbiota Transplantation ; *Hepatic Encephalopathy/therapy ; Humans ; }, abstract = {Early data suggest fecal microbiota transplant (FMT) may treat hepatic encephalopathy (HE). Optimal FMT donor and recipient characteristics are unknown. We assessed the safety and efficacy of FMT in patients with prior overt HE, comparing five FMT donors. We performed an open-label study of FMT capsules, administered 5 times over 3 weeks. Primary outcomes were change in psychometric HE score (PHES) and serious adverse events (SAEs). Serial stool samples underwent shallow shotgun metagenomic sequencing. Ten patients completed FMT administration and 6-month follow-up. Model for End-Stage Liver Disease (MELD) score did not change after FMT (14 versus 14, p = 0.51). Thirteen minor adverse events and three serious adverse events (two unrelated to FMT) were reported. One SAE was extended-spectrum beta-lactamase Escherichia coli bacteremia. The PHES improved after three doses of FMT (+2.1, p < 0.05), after five doses of FMT (+2.9, p = 0.007), and 4 weeks after the fifth dose of FMT (+3.1, p = 0.02). Mean change in the PHES ranged from -1 to +6 by donor. Two taxa were identified by random forest analysis and confirmed by linear regression to predict the PHES- Bifidobacterium adolescentis (adjusted R[2] = 0.27) and B. angulatum (adjusted R[2] = 0.25)-both short-chain fatty acid (SCFA) producers. Patients who responded to FMT had higher levels of Bifidobacterium as well as other known beneficial taxa at baseline and throughout the study. The FMT donor with poorest cognitive outcomes in recipients had the lowest fecal SCFA levels. Conclusion: FMT capsules improved cognition in HE, with an effect varying by donor and recipient factors (NCT03420482).}, }
@article {pmid35382170, year = {2022}, author = {Eriksen, LL and Baunwall, SMD and Eriksen, PL and Bak-Fredslund, KP and Nielsen, JE and Dahlerup, JF and Thomsen, KL and Vilstrup, H and Hvas, CL}, title = {Deep hyperammonemic hepatic encephalopathy precipitated by fecal microbiota transplantation for fulminant Clostridioides difficile infection.}, journal = {Gastroenterology report}, volume = {10}, number = {}, pages = {goab043}, pmid = {35382170}, issn = {2052-0034}, }
@article {pmid35382166, year = {2022}, author = {Yadav, M and Chauhan, NS}, title = {Microbiome therapeutics: exploring the present scenario and challenges.}, journal = {Gastroenterology report}, volume = {10}, number = {}, pages = {goab046}, pmid = {35382166}, issn = {2052-0034}, abstract = {Human gut-microbiome explorations have enriched our understanding of microbial colonization, maturation, and dysbiosis in health-and-disease subsets. The enormous metabolic potential of gut microbes and their role in the maintenance of human health is emerging, with new avenues to use them as therapeutic agents to overcome human disorders. Microbiome therapeutics are aimed at engineering the gut microbiome using additive, subtractive, or modulatory therapy with an application of native or engineered microbes, antibiotics, bacteriophages, and bacteriocins. This approach could overcome the limitation of conventional therapeutics by providing personalized, harmonized, reliable, and sustainable treatment. Its huge economic potential has been shown in the global therapeutics market. Despite the therapeutic and economical potential, microbiome therapeutics is still in the developing stage and is facing various technical and administrative issues that require research attention. This review aims to address the current knowledge and landscape of microbiome therapeutics, provides an overview of existing health-and-disease applications, and discusses the potential future directions of microbiome modulations.}, }
@article {pmid35382160, year = {2022}, author = {Burstiner, LS and Silver, J and Burstiner, LJ and Teymoorian, A and Pallav, K and Jones, D and Owings, A and Glover, S}, title = {Escherichia coli O157: H7 sepsis following fecal microbiota transplant in an IgA-deficient inflammatory bowel disease patient.}, journal = {Gastroenterology report}, volume = {10}, number = {}, pages = {goab041}, pmid = {35382160}, issn = {2052-0034}, }
@article {pmid35379265, year = {2022}, author = {Wang, H and Zhang, M and Li, J and Liang, J and Yang, M and Xia, G and Ren, Y and Zhou, H and Wu, Q and He, Y and Yin, J}, title = {Gut microbiota is causally associated with poststroke cognitive impairment through lipopolysaccharide and butyrate.}, journal = {Journal of neuroinflammation}, volume = {19}, number = {1}, pages = {76}, pmid = {35379265}, issn = {1742-2094}, support = {NSFC81870936//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Butyrates ; *Cognitive Dysfunction/etiology/psychology ; Dysbiosis/complications ; *Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides/toxicity ; Mice ; }, abstract = {BACKGROUND: Poststroke cognitive impairment (PSCI) is prevalent in stroke patients. The etiology of PSCI remains largely unknown. We previously found that stroke induces gut microbiota dysbiosis which affects brain injury. Hereby, we aimed to investigate whether the gut microbiota contributes to the pathogenesis of PSCI.<br><br>METHODS: 83 stroke patients were recruited and their cognitive function were measured by Montreal Cognitive Assessment (MoCA) scores 3&#xa0;months after stroke onset. The peripheral inflammatory factor levels and gut microbiota compositions of the patients were analyzed. Fecal microbiota transplantation from patients to stroke mice was performed to examine the causal relationship between the gut microbiota and PSCI. The cognitive function of mice was evaluated by Morris water maze test.<br><br>RESULTS: 34 and 49 stroke patients were classified as PSCI and non-PSCI, respectively. Compared with non-PSCI patients, PSCI patients showed significantly higher levels of gut Enterobacteriaceae, lipopolysaccharide (LPS) and peripheral inflammation markers. Consistently, stroke mice that received microbiota from PSCI patients (PSCI mice) presented a higher level of Enterobacteriaceae, intestinal Toll-like receptor-4 (TLR4) expression, circulating LPS, LPS-binding protein (LBP) and inflammatory cytokines, and a lower level of fecal butyrate, severer intestine destruction and cognitive impairment than mice that received microbiota from nPSCI patients (nPSCI mice). In addition, we observed exacerbations in blood-brain barrier (BBB) integrity, microglial activation, neuronal apoptosis in the CA1 region of the hippocampus, and A&#x3b2; deposition in the thalamus of PSCI mice in comparison with nPSCI mice. Intraperitoneal injection of LPS after stroke caused similar pathology to those seen in PSCI mice. Supplementation with sodium butyrate (NaB) via drinking water rescued these detrimental changes in PSCI mice.<br><br>CONCLUSIONS: Our data indicate a cause-effect relationship between gut microbiota and PSCI for the first time, which is likely mediated by inflammation-regulating metabolites including LPS and butyrate.}, }
@article {pmid35372517, year = {2022}, author = {Baquero, F and Del Campo, R and Martínez, JL}, title = {Interventions in Nicotinamide Adenine Dinucleotide Metabolism, the Intestinal Microbiota and Microcin Peptide Antimicrobials.}, journal = {Frontiers in molecular biosciences}, volume = {9}, number = {}, pages = {861603}, pmid = {35372517}, issn = {2296-889X}, abstract = {A proper NADH/NAD + balance allows for the flow of metabolic and catabolic activities determining cellular growth. In Escherichia coli, more than 80 NAD + dependent enzymes are involved in all major metabolic pathways, including the post-transcriptional build-up of thiazole and oxazole rings from small linear peptides, which is a critical step for the antibiotic activity of some microcins. In recent years, NAD metabolism boosting drugs have been explored, mostly precursors of NAD + synthesis in human cells, with beneficial effects on the aging process and in preventing oncological and neurological diseases. These compounds also enhance NAD + metabolism in the human microbiota, which contributes to these beneficial effects. On the other hand, inhibition of NAD + metabolism has been proposed as a therapeutic approach to reduce the growth and propagation of tumor cells and mitigating inflammatory bowel diseases; in this case, the activity of the microbiota might mitigate therapeutic efficacy. Antibiotics, which reduce the effect of microbiota, should synergize with NAD + metabolism inhibitors, but these drugs might increase the proportion of antibiotic persistent populations. Conversely, antibiotics might have a stronger killing effect on bacteria with active NAD + production and reduce the cooperation of NAD + producing bacteria with tumoral cells. The use of NADH/NAD + modulators should take into consideration the use of antibiotics and the population structure of the microbiota.}, }
@article {pmid35372103, year = {2022}, author = {Halaweish, HF and Boatman, S and Staley, C}, title = {Encapsulated Fecal Microbiota Transplantation: Development, Efficacy, and Clinical Application.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {826114}, pmid = {35372103}, issn = {2235-2988}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) has been established as a highly restorative therapeutic approach for treating recurrent Clostridioides difficile infection (rCDI). Recently, the use of capsule-based fecal microbiota transplantation (cFMT) has been shown to be a clinically effective approach to restore intestinal microbiota composition. This convenient, oral delivery provides an easy route of administration and a newfound flexibility for clinicians and patients. In this review, we discuss the development of cFMT, paying particular attention to lyophilized cFMT products. We review the available published clinical studies comparing cFMT with lower endoscopic FMT (eFMT) or placebo. We further discuss the pharmacokinetics of FMT, which should be understood in a framework of microbial ecology that considers the complex and dynamic interactions of gut microbiota with host factors and other microorganisms. Promisingly, the results of multiple trials investigating cFMT vs. eFMT in rCDI show cFMT to be as effective as eFMT at preventing rCDI. However, its efficacy in non-rCDI conditions, including obesity and metabolic syndrome, inflammatory bowel disease, HIV, and neurologic conditions, is less clear and more research is needed in these areas. Standardization of formulation, dose, and timing of administration to ensure optimal microbiota engraftment and clinical response is also a challenge to be addressed. Overall, cFMT is a practical method for fecal microbiota transplantation, with similar efficacy to eFMT in the resolution of rCDI, that holds therapeutic potential in a variety of other diseases.}, }
@article {pmid35371048, year = {2022}, author = {Brevi, A and Cogrossi, LL and Lorenzoni, M and Mattorre, B and Bellone, M}, title = {The Insider: Impact of the Gut Microbiota on Cancer Immunity and Response to Therapies in Multiple Myeloma.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {845422}, pmid = {35371048}, issn = {1664-3224}, mesh = {Disease Progression ; *Gastrointestinal Microbiome ; Humans ; *Monoclonal Gammopathy of Undetermined Significance ; *Multiple Myeloma/therapy ; Prognosis ; *Smoldering Multiple Myeloma ; }, abstract = {The human microbiota is a unique set of microorganisms colonizing the human body and evolving within it from the very beginning. Acting as an insider, the microbiota provides nutrients, and mutualistically interacts with the host's immune system, thus contributing to the generation of barriers against pathogens. While a strong link has been documented between intestinal dysbiosis (i.e., disruption to the microbiota homeostasis) and diseases, the mechanisms by which commensal bacteria impact a wide spectrum of mucosal and extramucosal human disorders have only partially been deciphered. This is particularly puzzling for multiple myeloma (MM), a treatable but incurable neoplasia of plasma cells that accumulate in the bone marrow and lead to end-organ damage. Here we revise the most recent literature on data from both the bench and the bedside that show how the gut microbiota modulates cancer immunity, potentially impacting the progression of asymptomatic monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM) to full blown MM. We also explore the effect of the gut microbiome on hematopoietic stem cell transplantation, chemotherapy, immunomodulating therapy and cancer immunotherapy in MM patients. Additionally, we identify the most cogent area of investigation that have the highest chance to delineate microbiota-related and pathobiology-based parameters for patient risk stratification. Lastly, we highlight microbiota-modulating strategies (i.e., diet, prebiotics, probiotics, fecal microbiota transplantation and postbiotics) that may reduce treatment-related toxicity in patients affected by MM as well as the rates of undertreatment of SMM patients.}, }
@article {pmid35370847, year = {2022}, author = {Huang, HL and Xu, HM and Liu, YD and Shou, DW and Chen, HT and Nie, YQ and Li, YQ and Zhou, YJ}, title = {First Application of Fecal Microbiota Transplantation in Adult Asperger Syndrome With Digestive Symptoms-A Case Report.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {695481}, pmid = {35370847}, issn = {1664-0640}, abstract = {Asperger syndrome (AS) is a chronic neurodevelopmental disorder. Although all of the clinically diagnosed cases display normal intelligence and speech functions, barriers in social interaction and communication seriously affect mental health and psychological function. In addition to traditional psychological/behavioral training and symptomatic medication, in-depth studies of intestinal microbiota and mental health have indicated that probiotics (e.g., Lactobacillus rhamnosus) can effectively reduce the occurrence of AS. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient's gastrointestinal tract to improve the gut microenvironment. In this case report, we describe the first case of adult AS treated with FMT. The patient suffered from diarrhea-predominant irritable bowel syndrome for 6 years with symptoms of diarrhea and abdominal pain. After three rounds of FMT, the diarrhea and abdominal pain were significantly improved. Moreover, the symptoms of AS were also significantly ameliorated. We found that FMT changed the structure of the intestinal microbiota as well as the patient's serum metabolites, and these changes were consistent with the patient's symptoms. The metabolites may affect signaling pathways, as revealed by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The changes in microbial metabolites following FMT may affect other regions (e.g., the nervous system) via the circulatory system, such that the bacteria-gut-blood-brain axis may be the means through which FMT mitigates AS.}, }
@article {pmid35370631, year = {2022}, author = {Huang, Y and Xin, W and Xiong, J and Yao, M and Zhang, B and Zhao, J}, title = {The Intestinal Microbiota and Metabolites in the Gut-Kidney-Heart Axis of Chronic Kidney Disease.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {837500}, pmid = {35370631}, issn = {1663-9812}, abstract = {Emerging evidences demonstrate the involvement of gut microbiota in the progression of chronic kidney disease (CKD) and CKD-associated complications including cardiovascular disease (CVD) and intestinal dysfunction. In this review, we discuss the interactions between the gut, kidney and heart in CKD state, and elucidate the significant role of intestinal microbiota in the gut-kidney-heart axis hypothesis for the pathophysiological mechanisms of these diseases, during which process mitochondria may serve as a potential therapeutic target. Dysregulation of this axis will lead to a vicious circle, contributing to CKD progression. Recent studies suggest novel therapies targeting gut microbiota in the gut-kidney-heart axis, including dietary intervention, probiotics, prebiotics, genetically engineered bacteria, fecal microbiota transplantation, bacterial metabolites modulation, antibiotics, conventional drugs and traditional Chinese medicine. Further, the identification of specific microbial communities and their corresponding pathophysiological metabolites and the illumination of the gut-kidney-heart axis may contribute to innovative basic research, clinical trials and therapeutic strategies against CKD progression and uremic complications in CKD patients.}, }
@article {pmid35365713, year = {2022}, author = {Smith, BJ and Piceno, Y and Zydek, M and Zhang, B and Syriani, LA and Terdiman, JP and Kassam, Z and Ma, A and Lynch, SV and Pollard, KS and El-Nachef, N}, title = {Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {5517}, pmid = {35365713}, issn = {2045-2322}, support = {T32 DK007007/DK/NIDDK NIH HHS/United States ; 5T32DK007007/NH/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; *Colitis, Ulcerative/etiology/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Remission Induction ; }, abstract = {Fecal microbiota transplant is a promising therapy for ulcerative colitis. Parameters maximizing effectiveness and tolerability are not yet clear, and it is not known how import the transmission of donor microbes to patients is. Here (clinicaltrails.gov: NCT03006809) we have tested the effects of antibiotic pretreatment and compared two modes of maintenance dose delivery, capsules versus enema, in a randomized, pilot, open-label, 2 × 2 factorial design with 22 patients analyzed with mild to moderate UC. Clinically, the treatment was well-tolerated with favorable safety profile. Of patients who received antibiotic pretreatment, 6 of 11 experienced remission after 6 weeks of treatment, versus 2 of 11 non-pretreated patients (log odds ratio: 1.69, 95% confidence interval: -0.25 to 3.62). No significant differences were found between maintenance dosing via capsules versus enema. In exploratory analyses, microbiome turnover at both the species and strain levels was extensive and significantly more pronounced in the pretreated patients. Associations were also revealed between taxonomic turnover and changes in the composition of primary and secondary bile acids. Together these findings suggest that antibiotic pretreatment contributes to microbiome engraftment and possibly clinical effectiveness, and validate longitudinal strain tracking as a powerful way to monitor the dynamics and impact of microbiota transfer.}, }
@article {pmid35364300, year = {2022}, author = {Veraldi, S and Maronese, CA and Nazzaro, G and Daprai, L}, title = {Anal pruritus caused by Dientamoeba fragilis.}, journal = {Travel medicine and infectious disease}, volume = {48}, number = {}, pages = {102319}, doi = {10.1016/j.tmaid.2022.102319}, pmid = {35364300}, issn = {1873-0442}, mesh = {*Dientamoeba ; Feces ; Humans ; *Pruritus ; }, }
@article {pmid35360442, year = {2022}, author = {Kumar, A and Al-Hassi, HO and Steed, H and Phipps, O and Brookes, MJ}, title = {Bile Acids and the Microbiome: Making Sense of This Dynamic Relationship in Their Role and Management in Crohn's Disease.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {2022}, number = {}, pages = {8416578}, pmid = {35360442}, issn = {2291-2797}, mesh = {Bile Acids and Salts ; *Crohn Disease/therapy ; *Gastrointestinal Microbiome/physiology ; Humans ; Intestines ; *Microbiota ; }, abstract = {BACKGROUND: Bile acids help maintain the physiological balance of the gut microbiome and the integrity of the intestinal epithelial barrier. Similarly, intestinal bacteria play a major role in bile acid metabolism as they are involved in crucial biotransformation steps in the enterohepatic circulation pathway. Understanding the relationship between bile acid signalling and the gut microbiome in Crohn's disease can help target new and innovative treatment strategies.<br><br>AIMS: This review summarises the relationship between bile acids and the microbiome in Crohn's disease and discusses potential novel therapeutic options.<br><br>METHODS: We performed a literature review on bile acid signalling, its effect on the gut microbiome, and therapeutic applications in Crohn's disease.<br><br>RESULTS: Current research suggests that there is a strong interplay between the dysregulated microbiota, bile acid metabolism, and the mucosal immune system that can result in a changed immunological function, triggering the inflammatory response in Crohn's disease. Recent studies have demonstrated an association with altering the enterohepatic circulation and activating the farnesoid X receptor signalling pathway with the use of probiotics and faecal microbial transplantation, respectively. Bile acid sequestrants have been shown to have anti-inflammatory, cytoprotective, and anti-apoptotic properties with the potential to alter the intestinal microbial composition, suggesting a possible role in inducing and maintaining Crohn's disease.<br><br>CONCLUSIONS: Active Crohn's disease has been correlated with changes in bacterial concentrations, which may be associated with changes in bile acid modification. Further research should focus on targeting these areas for future therapeutic options.}, }
@article {pmid35357354, year = {2022}, author = {Kim, SY and Shin, J and Park, JS and Cha, B and Seo, Y and Park, SH and Lee, JH and Kim, JS and Kwon, G}, title = {The first report on effect of fecal microbiota transplantation as a complementary treatment in a patient with steroid-refractory Cronkhite-Canada syndrome: A case report.}, journal = {Medicine}, volume = {101}, number = {12}, pages = {e29135}, pmid = {35357354}, issn = {1536-5964}, mesh = {Aged ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Humans ; *Intestinal Polyposis/therapy ; Male ; RNA, Ribosomal, 16S/genetics ; Steroids ; }, abstract = {RATIONALE: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease of unknown etiology that is characterized by the appearance of multiple polyps in the entire gastrointestinal (GI) tract, except in the esophagus, with GI and non-GI symptoms. Various factors are associated with the pathogenesis of CCS. Immune dysregulation has been discussed as one of the pathogeneses of CCS, and dysbiosis of the gut microbiota can affect the immune system. Currently, standard treatment has not been established.<br><br>We present the treatment with fecal microbiota transplantation (FMT) in a 67-year-old male patient with steroid-refractory CCS who could not undergo anti-tumor necrosis factor-a treatment due to suspected tuberculosis infection.<br><br>INTERVENTIONS: FMT has recently attracted attention as a method of overcoming drug resistance through immunomodulatory effects through microbiome regulation. We collected the patient's stool samples before FMT and 8weeks after FMT.<br><br>OUTCOMES: We analyzed the microbiome composition of patients by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). After FMT, the number of episodes of diarrhea and hypoalbuminemia were also corrected. The Chao 1 index after FMT, which was significantly higher than that of donors before FMT, changed to a similar level for donors after FMT. Fusobacterium nucleatum, Pyramidobacter piscolens, and Campylobacter concisus disappeared after FMT, suggesting the presence of an association between gut microbiota and CCS.<br><br>LESSONS: Furthermore, we provide the possibility that microbiome modulation by FMT could serve as a complementary treatment in patients with steroid-refractory CCS.}, }
@article {pmid35355860, year = {2022}, author = {Gao, T and Wang, Z and Cao, J and Dong, Y and Chen, Y}, title = {The Role of Aeromonas-Goblet Cell Interactions in Melatonin-Mediated Improvements in Sleep Deprivation-Induced Colitis.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {8133310}, pmid = {35355860}, issn = {1942-0994}, mesh = {*Aeromonas ; Animals ; Cell Communication ; *Colitis/chemically induced ; Glycogen Synthase Kinase 3 beta ; Goblet Cells ; *Melatonin/pharmacology/therapeutic use ; Mice ; Sleep Deprivation/complications/metabolism ; }, abstract = {BACKGROUND: Our previous studies demonstrated that melatonin could effectively ameliorate sleep deprivation- (SD-) caused oxidative stress-mediated gut microbiota disorder and colitis. The research further clarified the mechanism of melatonin in improving colitis from the perspective of the interaction between Aeromonas and goblet cells.<br><br>METHODS: A seventy-two hours SD mouse model with or without melatonin intervention and fecal microbiota transplantation (FMT) to explore the vital position of Aeromonas-goblet cell interactions in melatonin improving SD-induced colitis. Moreover, Aeromonas or LPS-supplied mice were assessed, and the influence of melatonin on Aeromonas-goblet cell interactions-mediated oxidative stress caused colitis. Furthermore, in vitro experiment investigated the regulation mechanism of melatonin.<br><br>RESULTS: Our study showed that SD induced colitis, with upregulation of Aeromonas and LPS levels and reductions in goblet cells number and MUC2 protein. Similarly, FMT from SD mice, Aeromonas veronii colonization, and LPS treatment restored the SD-like goblet cells number and MUC2 protein decrease and colitis. Moreover, LPS treatment downregulated the colonic antioxidant capacity. Yet, melatonin intervention reversed all consequence in SD, A.veronii colonization, and LPS-treated mice. In vitro, melatonin reversed A. veronii- or LPS-induced MUC2 depletion in mucus-secreting human HT-29 cells via increasing the expression level of Villin, Tff3, p-GSK-3&#x3b2;, &#x3b2;-catenin, and melatonin receptor 2 (MT2) and decreasing the level of p-I&#x3ba;B, p-P65, ROS, TLR4, and MyD88 proteins, while the improvement effect was blocked with pretreatment with a MT2 antagonist but were mimicked by TLR4 and GSK-3&#x3b2; antagonists and ROS scavengers.<br><br>CONCLUSIONS: Our results demonstrated that melatonin-mediated MT2 inhibits Aeromonas-goblet cell interactions to restore the level of MUC2 production via LPS/TLR4/MyD88/GSK-3&#x3b2;/ROS/NF-&#x3ba;B loop, further improving colitis in SD mice.}, }
@article {pmid35352757, year = {2022}, author = {Mejía-Granados, DM and Villasana-Salazar, B and Coan, AC and Rizzi, L and Balthazar, MLF and Godoi, AB and Canto, AMD and Rosa, DCD and Silva, LS and Tacla, RDR and Damasceno, A and Donatti, A and Avelar, WM and Sousa, A and Lopes-Cendes, I}, title = {Gut microbiome in neuropsychiatric disorders.}, journal = {Arquivos de neuro-psiquiatria}, volume = {80}, number = {2}, pages = {192-207}, pmid = {35352757}, issn = {1678-4227}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; }, abstract = {BACKGROUND: Neuropsychiatric disorders are a significant cause of death and disability worldwide. The mechanisms underlying these disorders include a constellation of structural, infectious, immunological, metabolic, and genetic etiologies. Advances in next-generation sequencing techniques have demonstrated that the composition of the enteric microbiome is dynamic and plays a pivotal role in host homeostasis and several diseases. The enteric microbiome acts as a key mediator in neuronal signaling via metabolic, neuroimmune, and neuroendocrine pathways.<br><br>OBJECTIVE: In this review, we aim to present and discuss the most current knowledge regarding the putative influence of the gut microbiome in neuropsychiatric disorders.<br><br>METHODS: We examined some of the preclinical and clinical evidence and therapeutic strategies associated with the manipulation of the gut microbiome.<br><br>RESULTS: targeted taxa were described and grouped from major studies to each disease.<br><br>CONCLUSIONS: Understanding the complexity of these ecological interactions and their association with susceptibility and progression of acute and chronic disorders could lead to novel diagnostic biomarkers based on molecular targets. Moreover, research on the microbiome can also improve some emerging treatment choices, such as fecal transplantation, personalized probiotics, and dietary interventions, which could be used to reduce the impact of specific neuropsychiatric disorders. We expect that this knowledge will help physicians caring for patients with neuropsychiatric disorders.}, }
@article {pmid35352640, year = {2023}, author = {Bhatt, S and Kanoujia, J and Mohana Lakshmi, S and Patil, CR and Gupta, G and Chellappan, DK and Dua, K}, title = {Role of Brain-Gut-Microbiota Axis in Depression: Emerging Therapeutic Avenues.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {22}, number = {2}, pages = {276-288}, doi = {10.2174/1871527321666220329140804}, pmid = {35352640}, issn = {1996-3181}, mesh = {Humans ; Mice ; Animals ; *Depressive Disorder, Major/therapy ; Anxiety ; Brain ; }, abstract = {The human gut microbiota plays a significant role in the pathophysiology of central nervous system-related diseases. Recent studies suggest correlations between the altered gut microbiota and major depressive disorder (MDD). It is proposed that normalization of the gut microbiota alleviates MDD. The imbalance of brain-gut-microbiota axis also results in dysregulation of the hypothalamicpituitary- adrenal (HPA) axis. This imbalance has a crucial role in the pathogenesis of depression. Treatment strategies with certain antibiotics lead to the depletion of useful microbes and thereby induce depression like effects in subjects. Microbiota is also involved in the synthesis of various neurotransmitters (NTs) like 5-hydroxy tryptamine (5-HT; serotonin), norepinephrine (NE) and dopamine (DA). In addition to NTs, the gut microbiota also has an influence on brain derived neurotrophic factor (BDNF) levels. Recent research findings have exhibited that transfer of stress prone microbiota in mice is also responsible for depression and anxiety-like behaviour in animals. The use of probiotics, prebiotics, synbiotics and proper diet have shown beneficial effects in the regulation of depression pathogenesis. Moreover, transplantation of fecal microbiota from depressed individuals to normal subjects also induces depression-like symptoms. With the precedence of limited therapeutic benefits from monoamine targeting drugs, the regulation of brain-gut microbiota is emerging as a new treatment modality for MDDs. In this review, we elaborate on the significance of brain-gut-microbiota axis in the progression of MDD, particularly focusing on the modulation of the gut microbiota as a mode of treating MDD.}, }
@article {pmid35349076, year = {2022}, author = {Sharma, A and Roy, A and Premkumar, M and Verma, N and Duseja, A and Taneja, S and Grover, S and Chopra, M and Dhiman, RK}, title = {Fecal microbiota transplantation in alcohol-associated acute-on-chronic liver failure: an open-label clinical trial.}, journal = {Hepatology international}, volume = {16}, number = {2}, pages = {433-446}, pmid = {35349076}, issn = {1936-0541}, mesh = {*Acute-On-Chronic Liver Failure/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Hepatitis, Alcoholic/therapy ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Alteration of gut microbiota is a crucial component implicated in its pathogenesis, whose modulation has been suggested as a potential therapeutic tool. We evaluated the safety of fecal microbiota transplantation (FMT) and its efficacy in improving short-term survival and clinical severity scores in patients with SAH-ACLF.<br><br>METHODS: Thirty-three patients [13 in the FMT arm; 20 in the standard of care arm (SOC)] with SAH-ACLF were included in this open-label study. A single FMT session was administered as a freshly prepared stool suspension from pre-identified healthy family member stool donors through a nasojejunal tube. Patients were followed up on days 7, 28, and 90.<br><br>RESULTS: Survival at 28 and 90 days was significantly better in the FMT arm (100% versus 60%, p&#x2009;=&#x2009;0.01; 53.84% versus 25%, p&#x2009;=&#x2009;0.02). Hepatic encephalopathy resolved in 100% versus 57.14% (FMT versus SOC, p&#x2009;=&#x2009;0.11) patients, while ascites resolved in 100% versus 40% survivors (p&#x2009;=&#x2009;0.04). Major adverse event rates, including spontaneous bacterial peritonitis and gastrointestinal bleeding, were similar in both groups (p&#x2009;=&#x2009;0.77; p&#x2009;=&#x2009;0.70). Median IL1beta decreased by&#xa0;21.39% (IQR -&#xa0;73.67 to 7.63) in the FMT group, whereas it increased in the SOC by 27.44% (IQR -&#xa0;0.88 to 128.11) (p&#x2009;=&#x2009;0.01). Percentage changes in bilirubin and ALT between baseline and day 7 emerged as predictors of 90-day mortality.<br><br>CONCLUSION: FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH-ACLF.<br><br>CLINICAL TRIAL NUMBER: NCT03827772 available from http://clinicaltrials.gov/ct2/show/NCT03827772 CTRI Reference number: CTRI/2019/02/017538 dated 7 February 2019.}, }
@article {pmid35347532, year = {2023}, author = {Fang, Z and Chen, M and Qian, J and Wang, C and Zhang, J}, title = {The Bridge Between Ischemic Stroke and Gut Microbes: Short-Chain Fatty Acids.}, journal = {Cellular and molecular neurobiology}, volume = {43}, number = {2}, pages = {543-559}, pmid = {35347532}, issn = {1573-6830}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Ischemic Stroke ; Fatty Acids, Volatile/pharmacology/therapeutic use ; Prebiotics ; }, abstract = {Short-chain fatty acids (SCFAs) are monocarboxylates produced by the gut microbiota (GM) and result from the interaction between diet and GM. An increasing number of studies about the microbiota-gut-brain axis (MGBA) indicated that SCFAs may be a crucial mediator in the MGBA, but their roles have not been fully clarified. In addition, there are few studies directly exploring the role of SCFAs as a potential regulator of microbial targeted interventions in ischemic stroke, especially for clinical studies. This review summarizes the recent studies concerning the relationship between ischemic stroke and GM and outlines the role of SCFAs as a bridge between them. The potential mechanisms by which SCFAs affect ischemic stroke are described. Finally, the beneficial effects of SFCAs-mediated therapeutic measures such as diet, dietary supplements (e.g., probiotics and prebiotics), fecal microbiota transplantation, and drugs on ischemic brain injury are also discussed.}, }
@article {pmid35346845, year = {2022}, author = {Chen, J and Wang, M and Zhang, P and Li, H and Qu, K and Xu, R and Guo, N and Zhu, H}, title = {Cordycepin alleviated metabolic inflammation in Western diet-fed mice by targeting intestinal barrier integrity and intestinal flora.}, journal = {Pharmacological research}, volume = {178}, number = {}, pages = {106191}, doi = {10.1016/j.phrs.2022.106191}, pmid = {35346845}, issn = {1096-1186}, mesh = {Animals ; Deoxyadenosines ; Diet, High-Fat/adverse effects ; Diet, Western/adverse effects ; *Gastrointestinal Microbiome ; Inflammation/complications/drug therapy ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred C57BL ; Obesity/metabolism ; }, abstract = {Metabolic inflammation is a crucial factor in the pathogenesis of obesity and promotes related complications. Accumulating evidence has indicated that regulating intestinal integrity and the gut microbiota may be new treatment strategies for metabolic inflammation and obesity. Cordycepin has been reported to improve obesity, but the mechanism is not yet clear. Here, we showed that cordycepin considerably alleviated systemic inflammation while reducing body weight gain and metabolic disorders in Western diet (WD)-fed mice. Further investigations showed that cordycepin significantly ameliorated WD-induced damage to the intestinal barrier and decreased the leakage of lipopolysaccharide (LPS) into the blood in mice by suppressing intestinal inflammation, oxidative stress damage, and decreasing intestinal epithelial cell apoptosis and pyroptosis. In addition, by using metagenomic sequencing, we found that cordycepin could also regulate the homeostasis of intestinal flora, including selectively increasing the abundance of Akkermansia muciniphila and reducing the production of fecal LPS. Besides, we demonstrated that the intestinal flora partially mediated the beneficial effects of cordycepin on improving intestinal barrier function, and obesity-related symptoms in WD-fed mice by a fecal microbiota transplantation experiment. Hence, our findings provided new insights into the role of cordycepin in improving metabolic inflammation and obesity from the perspective of regulating the intestinal barrier function and intestinal flora, and further provided data support for the utility of cordycepin in the treatment of obesity and its complications.}, }
@article {pmid35346337, year = {2022}, author = {Newsome, RC and Gharaibeh, RZ and Pierce, CM and da Silva, WV and Paul, S and Hogue, SR and Yu, Q and Antonia, S and Conejo-Garcia, JR and Robinson, LA and Jobin, C}, title = {Interaction of bacterial genera associated with therapeutic response to immune checkpoint PD-1 blockade in a United States cohort.}, journal = {Genome medicine}, volume = {14}, number = {1}, pages = {35}, pmid = {35346337}, issn = {1756-994X}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; T32 CA257923/CA/NCI NIH HHS/United States ; TL1 TR001428/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; *Carcinoma, Non-Small-Cell Lung ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors ; *Lung Neoplasms/drug therapy ; Mice ; Programmed Cell Death 1 Receptor ; United States ; }, abstract = {BACKGROUND: Recent studies show that human gut microbial composition can determine whether a patient is a responder or non-responder to immunotherapy but have not identified a common microbial signal shared by responding patients. The functional relationship between immunity, intestinal microbiota, and NSCLC response to immune checkpoint inhibitor/inhibition (ICI) in an American cohort remains unexplored.<br><br>METHODS: RNAlater-preserved fecal samples were collected from 65 pre-treatment (baseline) and post-treatment stage III/IV NSCLC patients undergoing ICI therapy, categorized as responders or non-responders according to RECIST criteria. Pooled and individual responder and non-responder microbiota were transplanted into a gnotobiotic mouse model of lung cancer and treated with ICIs. 16S rDNA and RNA sequencing was performed on patient fecal samples, 16S rDNA sequencing on mouse fecal samples, and flow cytometric analysis on mouse tumor tissue.<br><br>RESULTS: Responder patients have both a different microbial community structure than non-responders (P = 0.004) and a different bacterial transcriptome (PC2 = 0.03) at baseline. Taxa significantly enriched in responders include amplicon sequence variants (ASVs) belonging to the genera Ruminococcus, Akkermansia, and Faecalibacterium. Pooled and individual responder microbiota transplantation into gnotobiotic mice decreased tumor growth compared to non-responder colonized mice following ICI (P = 0.023, P = 0.019, P = 0.008, respectively). Responder tumors showed an increased anti-tumor cellular phenotype following ICI treatment. Responder mice are enriched with ASVs belonging to the genera Bacteroides, Blautia, Akkermansia, and Faecalibacterium. Overlapping taxa mapping between human and mouse cohorts correlated with tumor size and weight revealed a network highlighting responder-associated ASVs belonging to the genera Colidextribacter, Frisingicoccus, Marvinbryantia, and Blautia which have not yet been reported.<br><br>CONCLUSIONS: The role of isolate-specific function and bacterial gene expression in gut microbial-driven responsiveness to ICI has been underappreciated. This work supports further investigation using isolate-driven models to characterize the mechanisms underlying this phenomenon.}, }
@article {pmid35346170, year = {2022}, author = {Lehmann, J and Schreyer, I and Riedl, D and Tschuggnall, M and Giesinger, JM and Ninkovic, M and Huth, M and Kronberger, I and Rumpold, G and Holzner, B}, title = {Usability evaluation of the Computer-Based Health Evaluation System (CHES) eDiary for patients with faecal incontinence: a pilot study.}, journal = {BMC medical informatics and decision making}, volume = {22}, number = {1}, pages = {81}, pmid = {35346170}, issn = {1472-6947}, mesh = {Aged ; Computers ; *Fecal Incontinence/diagnosis ; Humans ; Pilot Projects ; Surveys and Questionnaires ; Taurine/analogs &amp; derivatives ; }, abstract = {BACKGROUND: Faecal incontinence (FI) is prevalent in 15-20% of elderly individuals and is frequently monitored in clinical trials and practice. Bowel diaries are the most common way to document FI, but, in clinical practice, are mainly used as paper-based versions. Electronic diaries (eDiaries) offer many potential benefits over paper-based diaries. The aim of this study was to develop and test an eDiary to document FI.<br><br>METHODS: We migrated a paper FI diary to an eDiary app based on the Computer-based Health Evaluation System (CHES). To assess usability, we conducted functionality and usability tests at two time points in a sample of patients with FI. In the first assessment, the eDiary functionalities were tested, patients completed the System Usability Scale (SUS, range 0-100) and compared the paper diary with the eDiary. We set a threshold for minimum acceptable average usability at 70 points. Patients were then instructed to use the eDiary for 2 days at home and contacted to report on their usage and completed the SUS a second time.<br><br>RESULTS: We recruited a sample of N&#x2009;=&#x2009;14 patients to use the eDiary. All patients were able to use all functionalities of the eDiary and only a few patients with lower technological literacy or access to devices (n&#x2009;=&#x2009;3) needed initial assistance. The mean usability rating given at the first time point was high with 88 points (SD 18, 95% CI 78.2-96.8) and most patients (n&#x2009;=&#x2009;10) reported they would prefer the eDiary over the paper-based version. Nine patients (n&#x2009;=&#x2009;9) participated in the follow-up assessment and the mean SUS rating at the second time point was 97 points (SD 7, 95% CI 92.8-100).<br><br>CONCLUSION: The eDiary showed excellent usability scores for the assessment of FI at both assessments. Generally, patients preferred the eDiary over the paper-based version. We recommend the eDiary for usage with patients who own and use a smartphone and discuss potential solutions for patients with lower technological literacy or access.}, }
@article {pmid35345829, year = {2022}, author = {Zhang, F and Zhou, Y and Chen, H and Jiang, H and Zhou, F and Lv, B and Xu, M}, title = {Curcumin Alleviates DSS-Induced Anxiety-Like Behaviors via the Microbial-Brain-Gut Axis.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {6244757}, pmid = {35345829}, issn = {1942-0994}, mesh = {Animals ; Anxiety/drug therapy ; Brain-Gut Axis ; *Curcumin/pharmacology/therapeutic use ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {The anxiety and depression caused by inflammatory bowel diseases (IBD) are known to greatly affect the mental health of patients. The mechanism of psychiatric disorders caused by IBD is not fully understood. Previous research has suggested that the gut microbiome plays a key role in IBD. Curcumin is a yellow polyphenol extracted from the rhizome of the ginger plant, which has been shown to have effects against both depression and anxiety. Research has indicated that curcumin affects the gut microbiome and exerts antianxiety and neuroprotective effects through the microbiota-gut-brain axis (MGB). However, whether curcumin can alleviate the psychiatric disorders caused by IBD and how curcumin affects the MGB axis through the gut microbiota have not been fully understood. Therefore, this study was aimed at determining the metabolic parameters and microbiological environment in the peripheral and central nervous system to determine the effects of curcumin against anxiety induced by dextran sulfate sodium salt (DSS) in mice. To elaborate on the link between the gut microbiota and how curcumin alleviates anxiety-like behaviors, we performed a fecal microbiota transplantation (FMT) experiment. The results suggested that curcumin can effectively relieve anxiety-like behaviors caused by DSS in mice. Further, curcumin treatment can alleviate disturbances in the gut microbiota and systemic disorders of lipid metabolism caused by DSS. Finally, through FMT, we verified that curcumin increased phosphatidylcholine in the prefrontal cortex of the mice and alleviated DSS-induced anxiety-like behaviors by modulating specific gut microbiota. We also revealed that Muribaculaceae may be a key part of the gut microbiota for curcumin to alleviate DSS-induced anxiety-like behaviors through the MGB axis.}, }
@article {pmid35345443, year = {2022}, author = {Fan, Y and Su, Q and Chen, J and Wang, Y and He, S}, title = {Gut Microbiome Alterations Affect Glioma Development and Foxp3 Expression in Tumor Microenvironment in Mice.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {836953}, pmid = {35345443}, issn = {2234-943X}, abstract = {Glioma is the most common malignant tumor of the central nervous system (CNS), with high degree of malignancy and poor prognosis. The gut microbiome (GM) is composed of microorganisms with different properties and functions, which play an important role in human physiology and biological activities. It has been proved that GM can affect the development of glioma through natural immunity, but whether GM can affect glioma through adaptive immunity and whether there are some microorganisms in the GM that may affect glioma growth still remain unclear. In our study, we evaluated the relationship between GM and glioma. We proved that (I) glioma growth can induce structural changes of mouse GM, including the decreased abundance of Bacteroidia and increased abundance of Firmicutes. (II) GM dysbiosis can downregulate Foxp3 expression in the brain and promote glioma growth. A balanced environment of GM can upregulate the expression of Foxp3 in the brain and delay the development of glioma. (III) The increased abundance of Bacteroidia is associated with accelerated glioma progression, while its decreased abundance is associated with delayed glioma progression, which may be one of the key microorganisms affecting glioma growth. This study is helpful to reveal the relationship between GM and glioma development and provide new ideas for adjuvant therapy of glioma.}, }
@article {pmid35344215, year = {2022}, author = {Noye Tuplin, EW and Alukic, E and Lowry, DE and Chleilat, F and Wang, W and Cho, NA and Sampsell, K and Sales, KM and Mayengbam, S and McCoy, KD and Reimer, RA}, title = {Dietary fiber combinations to mitigate the metabolic, microbial, and cognitive imbalances resulting from diet-induced obesity in rats.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {36}, number = {5}, pages = {e22269}, doi = {10.1096/fj.202101750R}, pmid = {35344215}, issn = {1530-6860}, mesh = {Animals ; Cognition ; Diet, High-Fat/adverse effects ; Dietary Fiber/pharmacology ; *Insulin Resistance ; Mice ; Obesity/metabolism ; Rats ; Resistant Starch ; Sucrose ; *beta-Glucans ; }, abstract = {Dietary fiber promotes a healthy gut microbiome and shows promise in attenuating the unfavorable microbial changes resulting from a high-fat/sucrose (HFS) diet. High-fiber diets consisting of oligofructose alone (HFS/O) or in combination with β-glucan (HFS/OB), resistant starch (HFS/OR), or β-glucan and resistant starch (HFS/OBR) were fed to diet-induced obese rats for 8 weeks to determine if these fibers could attenuate the obese phenotype. Only the HFS/O group displayed a decrease in body weight and body fat, but all fiber interventions improved insulin sensitivity and cognitive function. The HFS/O diet was the least effective at improving cognitive function and only the HFS/OB group showed improvements in glucose tolerance, thus highlighting the differential effects of fiber types. Hippocampal cytokines (IL-6, IL-10) were more pronounced in the HFS/OB group which coincided with the most time spend in the open arms of the elevated plus maze. All fiber groups showed an increase in beneficial Bifidobacterium and Lactobacillus abundance while the HFS group showed higher abundance of Clostridium. Fecal microbiota transplant from fiber-treated rats into germ-free mice did not alter body composition in the mice but did result in a higher abundance of Bacteroides in the HFS/O and HFS/OB groups compared to HFS. The HFS/OB recipient mice also had higher insulin sensitivity compared to the other groups. This study highlights the influence of dietary fiber type on metabolic and cognitive outcomes suggesting that the type of supplementation (single or combined fibers) could be tailored to specific targeted outcomes.}, }
@article {pmid35340247, year = {2022}, author = {Feng, H and He, L and Wang, Z and Pi, B and Liu, Z}, title = {Phillygenin Protects the Intestinal Barrier from Dysfunction via let-7b Signaling Pathway and Regulation of Intestinal Microbiota.}, journal = {Journal of healthcare engineering}, volume = {2022}, number = {}, pages = {4769709}, pmid = {35340247}, issn = {2040-2309}, mesh = {Animals ; *Colitis/chemically induced/metabolism ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Humans ; Lignans ; Mice ; Signal Transduction ; }, abstract = {The study investigates the positive effects of phillygenin on intestinal tight junction via the let-7b signaling pathway and the regulation of intestinal microbiota. The expression levels of tight junction proteins are determined through PCR and Western blot. DSS-induced mice colitis is used to verify the protective effects of phillygenin on intestinal barrier and tight junction. Fecal microbiota transplantation is used to verify the role intestinal microbiota. let-7b is detected in the colon tissues of patients with acute stercoral obstruction. Phillygenin could promote the expression of occludin, which might be inhibited by let-7b inhibitor. DSS-induced mice colitis showed that phillygenin could lower the colonic permeability and maintain the tight junction-associated proteins. The effects of phillygenin could be deprived by anti-let-7b and rescued by FMT of normal intestinal microbiota. Clinical samples verified a lower level of let-7b in stercoral obstruction patients. Phillygenin could protect the intestinal barrier from dysfunction via the signaling pathway of let-7b by regulating intestinal microbiota.}, }
@article {pmid35339829, year = {2022}, author = {Yang, J and Zhang, Z and Xie, Z and Bai, L and Xiong, P and Chen, F and Zhu, T and Peng, Q and Wu, H and Zhou, Y and Ma, Y and Zhang, Y and Chen, M and Gao, J and Tian, W and Shi, K and Du, Y and Duan, Y and Wang, H and Xu, Y and Kuang, YQ and Zhu, M and Yu, J and Wang, K}, title = {Metformin modulates microbiota-derived inosine and ameliorates methamphetamine-induced anxiety and depression-like withdrawal symptoms in mice.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {149}, number = {}, pages = {112837}, doi = {10.1016/j.biopha.2022.112837}, pmid = {35339829}, issn = {1950-6007}, mesh = {*Amphetamine-Related Disorders ; Animals ; Anxiety/metabolism ; Depression/chemically induced/drug therapy/microbiology ; Inosine ; *Metformin/pharmacology ; *Methamphetamine ; Mice ; *Microbiota ; Rats ; *Substance Withdrawal Syndrome/metabolism ; }, abstract = {BACKGROUND: Metformin exhibits therapeutic potential in behavioural deficits induced by methamphetamine (METH) in rats. Emerging studies suggest gut microbiota may impact psychiatric symptoms, but there is no direct evidence supporting metformin's participation in the pathophysiology of withdrawal symptoms via modulation of gut microbiota.<br><br>METHODS: In order to define the functional impacts of gut microbiota and metformin to the behavioural deficits during METH withdrawal, we utilized a combination of fecal microbiota transplantation (FMT), high-throughput sequencing, and untargeted metabolomics technologies.<br><br>RESULTS: First, METH addicts exhibited higher &#x3b1; diversity and distinct microbial structures compared to healthy controls. In particular, the relative abundance of Rikenellaceae was positively correlated with the severity of anxiety and depression. Second, both human-to-mouse and mouse-to-mouse FMTs confirmed that METH-altered-microbiota transplantation is sufficient to promote anxiety and depression-like behaviours in recipient germ-free mice, and these behavioural disturbances could be ameliorated by metformin. In-depth analysis revealed that METH significantly altered the bacterial composition and structure as well as relative abundance of several bacterial taxa and metabolites, including Rikenellaceae and inosine, respectively, whereas add-on metformin could remodel these alterations. Finally, the inosine complementation successfully restored METH-induced anxiety and depression-like behaviours in mice.<br><br>CONCLUSION: This study demonstrates that METH withdrawal-induced anxiety and depression-like behaviours are reversible and transmissible via gut microbiota in a mouse model. The therapeutic effects of metformin on psychiatric manifestations are associated with microbiota-derived metabolites, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.}, }
@article {pmid35339730, year = {2022}, author = {Kattner, AA}, title = {About gladiators and a sacred disease.}, journal = {Biomedical journal}, volume = {45}, number = {1}, pages = {1-8}, pmid = {35339730}, issn = {2320-2890}, mesh = {COVID-19 ; Child ; Clostridioides difficile ; Clostridium Infections ; Diet, Ketogenic ; *Drug Resistant Epilepsy/therapy ; Fecal Microbiota Transplantation ; Female ; Humans ; Treatment Outcome ; }, abstract = {In this special edition of the Biomedical Journal the reader gains an insight into drug-resistant epilepsy and according treatment approaches involving deep brain stimulation, the ketogenic diet and fecal microbiota transplant. Another emphasis is put on personalized medicine strategies, and covered in articles about the use of natriuretic peptides against cancer, along with an article about companion diagnostics involving extracellular vesicles. Recurrent infection with Clostridium difficile, associated risk factors and therapeutic options are discussed. We learn about a mechanism that helps Leishmania evade a host control mechanism, receive an update about human adenovirus and are presented with characteristic magnetic resonance neuroimaging in COVID-19 pediatric patients. An advanced assessment in pediatric septic shock and an improved model for a pediatric early warning system are proposed. Some of the genetic causes of renal hypomagnesemia are explored, the impact of air pollution on children is examined, and an antisiphon device is described for surgical treatment of hydrocephalus. The relation between energy metabolism, circadian rhythm and its influence on the ATPase in the SCN are investigated, and among others some of the genetics influencing smoking duration and lung cancer. Finally it is discussed how embryo quality can be improved in in vitro fertilization, and what impact high estradiol has on blastocyst implantation. The outcome of surgery to correct mandibular deficiency is assessed, and in two letters the inclusion of observational studies in the evaluation of clinical trials related to COVID-19 is elaborated.}, }
@article {pmid35337386, year = {2022}, author = {Podlesny, D and Arze, C and Dörner, E and Verma, S and Dutta, S and Walter, J and Fricke, WF}, title = {Metagenomic strain detection with SameStr: identification of a persisting core gut microbiota transferable by fecal transplantation.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {53}, pmid = {35337386}, issn = {2049-2618}, mesh = {Adult ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome/genetics ; Humans ; Metagenome ; Metagenomics ; Treatment Outcome ; }, abstract = {BACKGROUND: The understanding of how microbiomes assemble, function, and evolve requires metagenomic tools that can resolve microbiota compositions at the strain level. However, the identification and tracking of microbial strains in fecal metagenomes is challenging and available tools variably classify subspecies lineages, which affects their applicability to infer microbial persistence and transfer.<br><br>RESULTS: We introduce SameStr, a bioinformatic tool that identifies shared strains in metagenomes by determining single-nucleotide variants (SNV) in species-specific marker genes, which are compared based on a maximum variant profile similarity. We validated SameStr on mock strain populations, available human fecal metagenomes from healthy individuals and newly generated data from recurrent Clostridioides difficile infection (rCDI) patients treated with fecal microbiota transplantation (FMT). SameStr demonstrated enhanced sensitivity to detect shared dominant and subdominant strains in related samples (where strain persistence or transfer would be expected) when compared to other tools, while being robust against false-positive shared strain calls between unrelated samples (where neither strain persistence nor transfer would be expected). We applied SameStr to identify strains that are stably maintained in fecal microbiomes of healthy adults over time (strain persistence) and that successfully engraft in rCDI patients after FMT (strain engraftment). Taxonomy-dependent strain persistence and engraftment frequencies were positively correlated, indicating that a specific core microbiota of intestinal species is adapted to be competitive both in healthy microbiomes and during post-FMT microbiome assembly. We explored other use cases for strain-level microbiota profiling, as a metagenomics quality control measure and to identify individuals based on the persisting core gut microbiota.<br><br>CONCLUSION: SameStr provides for a robust identification of shared strains in metagenomic sequence data with sufficient specificity and sensitivity to examine strain persistence, transfer, and engraftment in human fecal microbiomes. Our findings identify a persisting healthy adult core gut microbiota, which should be further studied to shed light on microbiota contributions to chronic diseases. Video abstract.}, }
@article {pmid35334150, year = {2022}, author = {Ison, MG and Tan, M and Daud, A and Huang, P and Jiang, JX}, title = {Quantitative norovirus viral load is not affected by home storage of stool.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {24}, number = {3}, pages = {e13826}, pmid = {35334150}, issn = {1399-3062}, support = {HHSN272201600016C/AI/NIAID NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; HHSN273301600016C/AI/NIAID NIH HHS/United States ; UL1TR001422/TR/NCATS NIH HHS/United States ; }, mesh = {*Caliciviridae Infections ; Feces ; Humans ; *Norovirus/genetics ; RNA, Viral/analysis/genetics ; Real-Time Polymerase Chain Reaction ; Viral Load ; }, abstract = {In preparation of a clinical trial of norovirus treatment, there were concerns raised by FDA about risk of self-storage of stool from patients infected with norovirus affecting quantitative assessments of norovirus RNA. Specifically, most home freezers are frost-free and may expose the samples to multiple rounds of freeze-thaw. Stool samples collected by the study team were stored at different lengths in a frost-free freezer and at -80°C. Quantitative PCRs of norovirus were performed on all samples using the same assay. By all measures, there was no significant change in measured viral load with home storage.}, }
@article {pmid35333590, year = {2022}, author = {Puntillo, M and Segli, F and Champagne, CP and Raymond, Y and Vinderola, G}, title = {Functional Microbes and Their Incorporation into Foods and Food Supplements: Probiotics and Postbiotics.}, journal = {Annual review of food science and technology}, volume = {13}, number = {}, pages = {385-407}, doi = {10.1146/annurev-food-052720-011545}, pmid = {35333590}, issn = {1941-1421}, mesh = {Dietary Supplements ; Female ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Probiotics ; Quality of Life ; }, abstract = {Life expectancy has dramatically increased over the past 200 years, but modern life factors such as environmental exposure, antibiotic overuse, C-section deliveries, limited breast-feeding, and diets poor in fibers and microbes could be associated with the rise of noncommunicable diseases such as overweight, obesity, diabetes, food allergies, and colorectal cancer as well as other conditions such as mental disorders. Microbial interventions that range from transplanting a whole undefined microbial community from a healthy gut to an ill one, e.g., so-called fecal microbiota transplantation or vaginal seeding, to the administration of selected well-characterized microbes, either live (probiotics) or not (postbiotics), with efficacy demonstrated in clinical trials, may be effective tools to treat or prevent acute and chronic diseases that humans still face, enhancing the quality of life.}, }
@article {pmid35333331, year = {2022}, author = {Mitten, EK and Baffy, G}, title = {Microbiota transplantation in portal hypertension: promises and pitfalls.}, journal = {Clinical science (London, England : 1979)}, volume = {136}, number = {6}, pages = {425-429}, doi = {10.1042/CS20220029}, pmid = {35333331}, issn = {1470-8736}, mesh = {Animals ; Feces ; *Gastrointestinal Microbiome ; *Hypertension, Portal/etiology/therapy ; Liver Cirrhosis/pathology ; Rats ; Splanchnic Circulation/drug effects ; }, abstract = {In this commentary, we discuss new findings indicating that microbiota transplantation has favorable impact on portal hypertension (PH) in the experimental model of cirrhosis induced by bile duct ligation (BDL) (Huang et al.; Clin Sci (Lond) (2021) 135(24): 2709-2728, doi: 10.1042/CS20210602). Sinusoidal PH is an ominous outcome of advanced chronic liver disease, characterized by increased intrahepatic vascular resistance (IHVR), splanchnic hyperemia, and the development of portosystemic collaterals. In the work of Huang et al., microbiota transplantation not only alleviated splanchnic hyperdynamic circulation by improving vascular responsiveness and decreasing mesenteric angiogenesis, but also reduced blood flow in portosystemic collaterals. Surprisingly, however, microbiota transplantation had no effect on intrahepatic vasoconstriction in this experimental model. We discuss these observations in the context of recent literature showing that manipulation of the gut microbiota (either by transplantation or through the use of probiotics) may improve IHVR, which is one of the earliest abnormalities in the pathogenesis of sinusoidal PH. Further research is needed to explore the specific molecular and cellular targets associated with the correction of dysbiosis in liver disease.}, }
@article {pmid35332832, year = {2022}, author = {Crits-Christoph, A and Hallowell, HA and Koutouvalis, K and Suez, J}, title = {Good microbes, bad genes? The dissemination of antimicrobial resistance in the human microbiome.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2055944}, pmid = {35332832}, issn = {1949-0984}, support = {DP5 OD029603/OD/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Drug Resistance, Bacterial/genetics ; *Gastrointestinal Microbiome/genetics ; Genes, Bacterial ; Humans ; Metagenomics ; *Microbiota/genetics ; }, abstract = {A global rise in antimicrobial resistance among pathogenic bacteria has proved to be a major public health threat, with the rate of multidrug-resistant bacterial infections increasing over time. The gut microbiome has been studied as a reservoir of antibiotic resistance genes (ARGs) that can be transferred to bacterial pathogens via horizontal gene transfer (HGT) of conjugative plasmids and mobile genetic elements (the gut resistome). Advances in metagenomic sequencing have facilitated the identification of resistome modulators, including live microbial therapeutics such as probiotics and fecal microbiome transplantation that can either expand or reduce the abundances of ARG-carrying bacteria in the gut. While many different gut microbes encode for ARGs, they are not uniformly distributed across, or transmitted by, various members of the microbiome, and not all are of equal clinical relevance. Both experimental and theoretical approaches in microbial ecology have been applied to understand differing frequencies of ARG horizontal transfer between commensal microbes as well as between commensals and pathogens. In this commentary, we assess the evidence for the role of commensal gut microbes in encoding antimicrobial resistance genes, the degree to which they are shared both with other commensals and with pathogens, and the host and environmental factors that can impact resistome dynamics. We further discuss novel sequencing-based approaches for identifying ARGs and predicting future transfer events of clinically relevant ARGs from commensals to pathogens.}, }
@article {pmid35329018, year = {2022}, author = {Storz, MA and Lombardo, M and Rizzo, G and Müller, A and Lederer, AK}, title = {Bowel Health in U.S. Shift Workers: Insights from a Cross-Sectional Study (NHANES).}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35329018}, issn = {1660-4601}, mesh = {*Circadian Rhythm ; Constipation ; Cross-Sectional Studies ; *Gastritis ; Humans ; Nutrition Surveys ; }, abstract = {Working outside of regular daytime hours is increasingly common in current societies and poses a substantial challenge to an individual's biological rhythm. Disruptions of the gastrointestinal tract's circadian rhythm and poor dietary choices subsequent to shiftwork may predispose the shift workforce to an increased risk of gastrointestinal disorders, including constipation, peptic ulcer disease, and erosive gastritis. We investigated bowel health in a US population of shift workers, using data from the National Health and Nutrition Examination Survey, and compared bowel movement (BM) frequency and defecation patterns between 2007 day workers and 458 shift workers (representing 55,305,037 US workers). Using bivariate and multivariate logistic regression techniques, our results suggested no association between shiftwork status and BM frequency, bowel leakage of gas, and stool consistency. Constipation prevalence was high but comparable in both groups (6.90% vs. 7.09%). The low fiber intake observed in both groups (15.07 vs. 16.75 g/day) could play a potential role here. The two groups did not differ with regard to other nutrients that may influence BM frequency and stool consistency (e.g., carbohydrate or caffeine intake). Additional studies including food group analyses and fecal biomarkers are warranted for a better understanding of GI health in shift workers.}, }
@article {pmid35325852, year = {2022}, author = {Du, L and Li, Q and Yi, H and Kuang, T and Tang, Y and Fan, G}, title = {Gut microbiota-derived metabolites as key actors in type 2 diabetes mellitus.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {149}, number = {}, pages = {112839}, doi = {10.1016/j.biopha.2022.112839}, pmid = {35325852}, issn = {1950-6007}, mesh = {*Diabetes Mellitus, Type 2/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {Type 2 diabetes mellitus (T2DM) is one of the most risk factors threatening human health. Although genetic and environmental factors contribute to the development of T2DM, gut microbiota has also been found to be involved. Gut microbiota-derived metabolites are a key factor in host-microbe crosstalk, and have been revealed to play a central role in the physiology and physiopathology of T2DM. In this review, we provide a timely and comprehensive summary of the microbial metabolites that are protective or causative for T2DM, including some amino acids-derived metabolites, short-chain fatty acids, trimethylamine N-oxide, and bile acids. The mechanisms by which metabolites affect T2DM have been elaborated. Knowing more about these processes will increase our understanding of the causal relationship between gut microbiota and T2DM. Moreover, some frontier therapies that target gut microbes and their metabolites to improve T2DM, including dietary intervention, fecal microbiota transplantation, probiotics, prebiotics or synbiotics intervention, and drugging microbial metabolism, have been critically discussed. This review may provide novel insights for the development of targeted and personalized treatments for T2DM based on gut microbial metabolites. More high-quality clinical trials are needed to accelerate the clinical translation of gut-targeted therapies for T2DM.}, }
@article {pmid35317350, year = {2022}, author = {Cassidy, H and Schuele, L and Lizarazo-Forero, E and Couto, N and Rossen, JWA and Friedrich, AW and van Leer-Buter, C and Niesters, HGM}, title = {Exploring a prolonged enterovirus C104 infection in a severely ill patient using nanopore sequencing.}, journal = {Virus evolution}, volume = {8}, number = {1}, pages = {veab109}, pmid = {35317350}, issn = {2057-1577}, abstract = {Chronic enterovirus infections can cause significant morbidity, particularly in immunocompromised patients. This study describes a fatal case associated with a chronic untypeable enterovirus infection in an immunocompromised patient admitted to a Dutch university hospital over nine months. We aimed to identify the enterovirus genotype responsible for the infection and to determine potential evolutionary changes. Long-read sequencing was performed using viral targeted sequence capture on four respiratory and one faecal sample. Phylogenetic analysis was performed using a maximum likelihood method, along with a root-to-tip regression and time-scaled phylogenetic analysis to estimate evolutionary changes between sample dates. Intra-host variant detection, using a Fixed Ploidy algorithm, and selection pressure, using a Fixed Effect Likelihood and a Mixed Effects Model of Evolution, were also used to explore the patient samples. Near-complete genomes of enterovirus C104 (EV-C104) were recovered in all respiratory samples but not in the faecal sample. The recovered genomes clustered with a recently reported EV-C104 from Belgium in August 2018. Phylodynamic analysis including ten available EV-C104 genomes, along with the patient sequences, estimated the most recent common ancestor to occur in the middle of 2005 with an overall estimated evolution rate of 2.97 × 10[-3] substitutions per year. Although positive selection pressure was identified in the EV-C104 reference sequences, the genomes recovered from the patient samples alone showed an overall negative selection pressure in multiple codon sites along the genome. A chronic infection resulting in respiratory failure from a relatively rare enterovirus was observed in a transplant recipient. We observed an increase in single-nucleotide variations between sample dates from a rapidly declining patient, suggesting mutations are weakly deleterious and have not been purged during selection. This is further supported by the persistence of EV-C104 in the patient, despite the clearance of other viral infections. Next-generation sequencing with viral enrichment could be used to detect and characterise challenging samples when conventional workflows are insufficient.}, }
@article {pmid35316318, year = {2022}, author = {Liu, Z and Yan, C and Lin, X and Ai, C and Dong, X and Shao, L and Wang, S and Song, S and Zhu, B}, title = {Responses of the gut microbiota and metabolite profiles to sulfated polysaccharides from sea cucumber in humanized microbiota mice.}, journal = {Food &amp; function}, volume = {13}, number = {7}, pages = {4171-4183}, doi = {10.1039/d1fo04443e}, pmid = {35316318}, issn = {2042-650X}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Microbiota ; Polysaccharides/chemistry/pharmacology ; *Sea Cucumbers/chemistry ; Sulfates/chemistry ; }, abstract = {Sea cucumber Stichopus japonicus has been consumed as functional food traditionally in Asia, and its sulfated polysaccharide (SCSPsj) demonstrates health-promoting effects in rodents which are related to the regulation of the gut microbiota. However, little is known about the response of the human gut microbiota to SCSPsj. Therefore, the present study aimed to study the response of the donor microbiota to SCSPsj in vivo through a humanized microbiota mice model, which was constructed by antibiotic treatment combined with fecal microbiota transplant. The results revealed that the SCSPsj supplement could positively interact with the specific donor microbiota. It could significantly regulate the gut microbiota community, especially the abundance of Lactobacillus. In addition, SCSPsj could modulate the metabolites in serum and cecal contents of mice, including short-chain fatty acids (SCFAs) and lactic acid, and the changes of some bioactive metabolites were associated with the gut microbiota enriched by SCSPsj. Furthermore, in vitro experiments demonstrated that the Lactobacillus strains isolated could not be proliferated directly by SCSPsj, but SCSPsj significantly promoted biofilm formation and mucus binding of Lactobacillus spp., which contributed to the enrichment of Lactobacillus in vivo. The present study could provide insight into the application of SCSPsj as microbiota-directed food.}, }
@article {pmid35314754, year = {2022}, author = {Menden, A and Hall, D and Hahn-Townsend, C and Broedlow, CA and Joshi, U and Pearson, A and Crawford, F and Evans, JE and Klatt, N and Crynen, S and Mullan, M and Ait-Ghezala, G}, title = {Exogenous lipase administration alters gut microbiota composition and ameliorates Alzheimer's disease-like pathology in APP/PS1 mice.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {4797}, pmid = {35314754}, issn = {2045-2322}, mesh = {*Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Clostridiales/metabolism ; Disease Models, Animal ; *Gastrointestinal Microbiome/physiology ; Lipase ; Memory Disorders ; Mice ; Mice, Transgenic ; }, abstract = {Alzheimer's disease (AD) represents the most common form of dementia in the elderly with no available disease modifying treatments. Altered gut microbial composition has been widely acknowledged as a common feature of AD, which potentially contributes to progression or onset of AD. To assess the hypothesis that Candida rugosa lipase (CRL), which has been shown to enhance gut microbiome and metabolite composition, can rebalance the gut microbiome composition and reduce AD pathology, the treatment effects in APPswe/PS1de9 (APP/PS1) mice were investigated. The analysis revealed an increased abundance of Acetatifactor and Clostridiales vadin BB60 genera in the gut; increased lipid hydrolysis in the gut lumen, normalization of peripheral unsaturated fatty acids, and reduction of neuroinflammation and memory deficits post treatment. Finally, we demonstrated that the evoked benefits on memory could be transferred via fecal matter transplant (FMT) into antibiotic-induced microbiome-depleted (AIMD) wildtype mice, ameliorating their memory deficits. The findings herein contributed to improve our understanding of the role of the gut microbiome in AD's complex networks and suggested that targeted modification of the gut could contribute to amelioration of AD neuropathology.}, }
@article {pmid35313729, year = {2022}, author = {Li, M and Li, K and Tang, S and Lv, Y and Wang, Q and Wang, Z and Luo, B and Niu, J and Zhu, Y and Guo, W and Bai, W and Wang, E and Xia, D and Wang, Z and Li, X and Yuan, J and Yin, Z and Trebicka, J and Han, G}, title = {Restoration of the gut microbiota is associated with a decreased risk of hepatic encephalopathy after TIPS.}, journal = {JHEP reports : innovation in hepatology}, volume = {4}, number = {5}, pages = {100448}, pmid = {35313729}, issn = {2589-5559}, abstract = {BACKGROUND &amp; AIMS: Hepatic encephalopathy (HE) is a major complication after transjugular intrahepatic portosystemic shunt (TIPS) and is primarily influenced by the gut microbiota. We aimed to evaluate alterations in the microbiota after TIPS and the association between such alterations and HE.<br><br>METHODS: We conducted a prospective longitudinal study of 106 patients with cirrhosis receiving TIPS. Faecal samples were collected before and after TIPS, and the gut microbiota was analysed by 16S ribosomal RNA sequencing.<br><br>RESULTS: Among all patients, 33 developed HE (HE+ group) within 6 months after TIPS and 73 did not (HE- group), and 18 died during follow-up. After TIPS, the autochthonous taxa increased, whereas the potential pathogenic taxa decreased in the HE- group, and the autochthonous taxon Lachnospiraceae decreased in the HE+ group. Furthermore, synergism among harmful bacteria was observed in all patients, which was weakened in the HE- group (p <0.001) but enhanced in the HE+ group (p <0.01) after TIPS. Variations of 5 autochthonous taxa, namely, Coprococcus, Ruminococcus, Blautia, Ruminococcaceae_uncultured, and Roseburia, were negatively correlated with the severity of HE. Notably, increased abundances of Coprococcus and Ruminococcus were protective factors against HE, and the incidences of HE in patients with improved, stable, and deteriorated microbiota after TIPS were 13.3, 25.9, and 68.2%, respectively. Higher total bilirubin level, Child-Pugh score, model for end-stage liver disease score, Granulicatella, and Alistipes and lower Subdoligranulum before TIPS were the independent risk factors for death.<br><br>CONCLUSIONS: Alterations in gut dysbiosis were negatively related to the occurrence and severity of post-TIPS HE, and the pre-TIPS microbiota were associated with death, suggesting the gut microbiota could be a promising potential biological target for screening suitable patients receiving TIPS and prevention and treatment of post-TIPS HE.<br><br>LAY SUMMARY: Alterations in the gut microbiota after transjugular intrahepatic portosystemic shunt (TIPS) and the relationship between such alterations and post-TIPS hepatic encephalopathy (HE) remain unclear. We therefore performed this study and found that after TIPS, restoration of the gut microbiota, mainly characterised by expansion of autochthonous taxa, depletion of harmful taxa, and weakening of synergism among harmful bacteria, was inversely related to the occurrence and severity of post-TIPS HE.}, }
@article {pmid35312296, year = {2022}, author = {Ju, Z and Shen, L and Zhou, M and Luo, J and Yu, Z and Qu, C and Lei, R and Lei, M and Huang, R}, title = {Helicobacter pylori and Alzheimer's Disease-Related Metabolic Dysfunction: Activation of TLR4/Myd88 Inflammation Pathway from p53 Perspective and a Case Study of Low-Dose Radiation Intervention.}, journal = {ACS chemical neuroscience}, volume = {13}, number = {7}, pages = {1065-1081}, doi = {10.1021/acschemneuro.2c00082}, pmid = {35312296}, issn = {1948-7193}, mesh = {*Alzheimer Disease ; Animals ; *Helicobacter Infections ; *Helicobacter pylori ; Humans ; Inflammation ; Mice ; Myeloid Differentiation Factor 88/genetics ; Toll-Like Receptor 4/genetics ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Gut dysbiosis is observed in Alzheimer's disease (AD) and is frequently associated with AD-induced metabolic dysfunction. However, the extent and specific underlying molecular mechanisms triggered by alterations of gut microbiota composition and function mediating AD-induced metabolic dysfunction in AD remain incompletely uncovered. Here, we indicate that Helicobacter pylori (H. pylori) is abundant in AD patients with relative metabolic dysfunction. Fecal microbiota transplantation from the AD patients promoted metabolic dysfunction in mice and increased gut permeability. H. pylori increased gut permeability through activation of the TLR4/Myd88 inflammation pathway in a p53-dependent manner, leading to metabolic dysfunction. Moreover, p53 deficiency reduced bile acid concentration, leading to an increased abundance of H. pylori colonization. Overall, these data identify H. pylori as a key promoter of AD-induced metabolic dysfunction.}, }
@article {pmid35312112, year = {2022}, author = {Wang, Y and Xu, Y and Xu, X and Wang, H and Wang, D and Yan, W and Zhu, J and Hao, H and Wang, G and Cao, L and Zhang, J}, title = {Ginkgo biloba extract ameliorates atherosclerosis via rebalancing gut flora and microbial metabolism.}, journal = {Phytotherapy research : PTR}, volume = {36}, number = {6}, pages = {2463-2480}, doi = {10.1002/ptr.7439}, pmid = {35312112}, issn = {1099-1573}, support = {81720108032//National Natural Science Foundation of China/ ; 81773986//National Natural Science Foundation of China/ ; 81930109//National Natural Science Foundation of China/ ; 81973559//National Natural Science Foundation of China/ ; G20582017001//Overseas Expertise Introduction Project for Discipline Innovation/ ; SZSM201801060//Sanming Project of Medicine in Shenzhen/ ; SKLNMZZ202020//the Project of State Key Laboratory of Natural Medicines, China Pharmaceutical University/ ; }, mesh = {Animals ; *Atherosclerosis/drug therapy/metabolism ; *Gastrointestinal Microbiome ; Ginkgo biloba ; Inflammation/drug therapy ; Mice ; Plant Extracts/pharmacology/therapeutic use ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The Ginkgo biloba leave extract (GbE) is widely applied in the prevention and treatment of atherosclerotic cardiovascular diseases in clinical practice. However, its mechanism of actions has not been totally elucidated. In this study, we confirmed the beneficial effects of GbE in alleviating hypercholesterolemia, inflammation and atherosclerosis in Ldlr[-/-] mice, which were fed 12 weeks of Western diet (WD). Moreover, 16S rRNA sequencing revealed that GbE treatment reshaped the WD-perturbed intestinal microbiota, particularly decreased the Firmicutes/Bacteroidetes ratio and elevated the abundance of Akkermansia, Alloprevotella, Alistipes, and Parabacteroides. Furthermore, GbE treatment downregulated the intestinal transcriptional levels of proinflammatory cytokines and enhanced the expression of tight junction proteins, exerting the roles of attenuating the intestinal inflammation as well as repairing the gut barrier. Meanwhile, the targeted metabolomic analysis displayed that GbE treatment significantly reversed the dysfunction of the microbial metabolic phenotypes, including promoting the production of short chain fatty acids, indole-3-acetate and secondary bile acids, which were correlated with the atherosclerotic plaque areas. Finally, we confirmed GbE-altered gut microbiota was sufficient to alleviate atherosclerosis by fecal microbiota transplantation. In summary, our findings provide important insights into the pharmacological mechanism underlying the antiatherogenic efficacy of GbE.}, }
@article {pmid35310733, year = {2022}, author = {Tominaga, K and Tsuchiya, A and Mizusawa, T and Matsumoto, A and Minemura, A and Oka, K and Takahashi, M and Yoshida, T and Kojima, Y and Ogawa, K and Kawata, Y and Nakajima, N and Kimura, N and Abe, H and Setsu, T and Takahashi, K and Sato, H and Ikarashi, S and Hayashi, K and Mizuno, KI and Yokoyama, J and Tajima, Y and Nakano, M and Shimada, Y and Kameyama, H and Wakai, T and Terai, S}, title = {Utility of autologous fecal microbiota transplantation and elucidation of microbiota in diversion colitis.}, journal = {DEN open}, volume = {2}, number = {1}, pages = {e63}, pmid = {35310733}, issn = {2692-4609}, abstract = {OBJECTIVES: Diversion colitis (DC) is an inflammatory disorder caused by interruption of the fecal stream and subsequent nutrient deficiency from luminal bacteria. The utility of fecal microbiota transplantation (FMT) for DC was recently investigated; however, the precise pathogenesis of this condition remains unclear. This study aimed to evaluate the utility of autologous FMT in DC and to determine the related changes in the intestinal microbiota.<br><br>METHODS: Autologous FMT was performed to reestablish the intestinal microbiota in five patients (average age, 64.6 &#xb1; 8.3 years) with DC. They underwent double-ended colostomy. We assessed the diverted colon by endoscopy and evaluated the microbiota before and after FMT using the 16S rRNA gene sequencing method.<br><br>RESULTS: All five patients had mild inflammation (ulcerative colitis endoscopic index of severity [UCEIS] 2-3) in the diverted colon based on the colonoscopic findings. Three patients presented with symptoms, such as tenesmus, mucoid stool, and bloody stool. With FMT treatment, all patients achieved endoscopic remission (UCEIS score of 0 or 1) and symptomatic improvement. We observed a significantly decreased &#x3b1;-diversity in DC patients compared to healthy controls. The frequency of aerobic bacteria, such as Enterobacteriaceae, in the diverted colon decreased after autologous FMT.<br><br>CONCLUSIONS: This study was the first to show that the microbiota in the diverted colon was significantly affected by autologous FMT. Since interruption of the fecal stream is central to the development of DC, FMT can be considered a promising treatment.}, }
@article {pmid35309933, year = {2022}, author = {Liu, J and Gao, Z and Liu, C and Liu, T and Gao, J and Cai, Y and Fan, X}, title = {Alteration of Gut Microbiota: New Strategy for Treating Autism Spectrum Disorder.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {792490}, pmid = {35309933}, issn = {2296-634X}, abstract = {Autism spectrum disorder (ASD) is defined as a complex heterogeneous disorder and characterized by stereotyped behavior and deficits in communication and social interactions. The emerging microbial knowledge has pointed to a potential link between gut microbiota dysbiosis and ASD. Evidence from animal and human studies showed that shifts in composition and activity of the gut microbiota may causally contribute to the etiopathogenesis of core symptoms in the ASD individuals with gastrointestinal tract disturbances and act on microbiota-gut-brain. In this review, we summarized the characterized gut bacterial composition of ASD and the involvement of gut microbiota and their metabolites in the onset and progression of ASD; the possible underlying mechanisms are also highlighted. Given this correlation, we also provide an overview of the microbial-based therapeutic interventions such as probiotics, antibiotics, fecal microbiota transplantation therapy, and dietary interventions and address their potential benefits on behavioral symptoms of ASD. The precise contribution of altering gut microbiome to treating core symptoms in the ASD needs to be further clarified. It seemed to open up promising avenues to develop microbial-based therapies in ASD.}, }
@article {pmid35309161, year = {2022}, author = {Gau, JT and Patel, P and Pan, JJ and Kao, TC}, title = {Analyzing fecal loading and retention patterns by abdominal X-rays of hospitalized older adults: A retrospective study.}, journal = {Aging medicine (Milton (N.S.W))}, volume = {5}, number = {1}, pages = {38-44}, pmid = {35309161}, issn = {2475-0360}, abstract = {BACKGROUND: Aging may affect ascending colon (AC) differently from descending colon (DC) and increase the risk of fecal loading (FL) in AC.<br><br>METHODS: Patients aged &#x2265;65&#xa0;years admitted to a community hospital were analyzed by abdominal x-ray for fecal loads and stool retention patterns. FL was scored between 0 and 5 (severe) on each segment of colon with a possible total score 20. Mean segment scores &#x2265;3.5 were designated as high scores for both AC and DC. Logistic regression was performed between groups to identify factors associated with FL patterns.<br><br>RESULTS: Groups identified were high FL in both AC and DC (N&#xa0;=&#xa0;21, 17.2%), FL predominantly in AC (N&#xa0;=&#xa0;38, 31.1%), low FL in both AC and DC (N=60, 49.2%), and FL low in AC and high in DC (N&#xa0;=&#xa0;3, 2.5%). Among 71 patients with total FL scores &#x2265;13 (indicating significant stool retention), 37 (52.1%) had the FL predominantly in AC. Patients prescribed antibiotic(s) prior to hospitalization had lower odds of FL predominantly in AC (adjusted odds ratio&#xa0;=&#xa0;0.18, 95% confidence interval = 0.04-0.84) compared to the group of low FL in both AC and DC with the adjustment of confounders.<br><br>CONCLUSION: This study found that 52.1% of those with significant stool retention on x-ray had the FL predominantly in AC. Antibiotic use was associated with lower odds of having FL predominately in AC. This study provided insights of FL distribution in colon and AC could be an area for significant stool burden in older adults with stool retention.}, }
@article {pmid35308555, year = {2022}, author = {Cao, C and Zhu, H and Yao, Y and Zeng, R}, title = {Gut Dysbiosis and Kidney Diseases.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {829349}, pmid = {35308555}, issn = {2296-858X}, abstract = {Gut dysbiosis is defined as disorders of gut microbiota and loss of barrier integrity, which are ubiquitous on pathological conditions and associated with the development of various diseases. Kidney diseases are accompanied with gut dysbiosis and metabolic disorders, which in turn contribute to the pathogenesis and progression of kidney diseases. Microbial alterations trigger production of harmful metabolites such as uremic toxins and a decrease in the number of beneficial ones such as SCFAs, which is the major mechanism of gut dysbiosis on kidney diseases according to current studies. In addition, the activation of immune responses and mitochondrial dysfunction by gut dysbiosis, also lead to the development of kidney diseases. Based on the molecular mechanisms, modification of gut dysbiosis via probiotics, prebiotics and synbiotics is a potential approach to slow kidney disease progression. Fecal microbiota transplantation (FMT) and genetic manipulation of the gut microbiota are also promising choices. However, the clinical use of probiotics in kidney disease is not supported by the current clinical evidence. Further studies are necessary to explore the causal relationships of gut dysbiosis and kidney diseases, the efficiency and safety of therapeutic strategies targeting gut-kidney axis.}, }
@article {pmid35308525, year = {2022}, author = {Chen, L and Zhu, Y and Hou, X and Yang, L and Chu, H}, title = {The Role of Gut Bacteria and Fungi in Alcohol-Associated Liver Disease.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {840752}, pmid = {35308525}, issn = {2296-858X}, abstract = {Cirrhosis and liver cancer caused by alcohol-associated liver disease (ALD) are serious threats to people's health. In addition to hepatic cell apoptosis and liver inflammation caused by oxidative stress during alcohol metabolism, intestinal microbiota disorders are also involved in the onset and development of ALD. Ethanol and its' oxidative and non-oxidative metabolites, together with dysbiosis-caused-inflammation, destroys the intestinal barrier. Changes of several microbial metabolites, such as bile acids, short-chain fatty acids, and amino acid, are closely associated with gut dysbiosis in ALD. The alcohol-caused dysbiosis can further influence intestinal barrier-related proteins, such as mucin2, bile acid-related receptors, and aryl hydrocarbon receptor (AhR), and these abnormal changes also participate in the injury of the intestinal barrier and hepatic steatosis. Gut-derived bacteria, fungi, and their toxins, such as lipopolysaccharide (LPS) and β-glucan translocate into the liver through the damaged intestinal barrier and promote the progression of inflammation and fibrosis of ALD. Thus, the prevention of alcohol-induced disruption of intestinal permeability has a beneficial effect on ALD. Currently, multiple therapeutic treatments have been applied to restore the gut microbiota of patients with ALD. Fecal microbial transplantation, probiotics, antibiotics, and many other elements has already shown their ability of restoring the gut microbiota. Targeted approaches, such as using bacteriophages to remove cytolytic Enterococcus faecalis, and supplement with Lactobacillus, Bifidobacterium, or boulardii are also powerful therapeutic options for ALD.}, }
@article {pmid35307002, year = {2022}, author = {Singhal, S and Rani, V}, title = {Therapeutic Effects of Gut Microbiota on Metabolic Syndrome: A Patent Review.}, journal = {Recent advances in food, nutrition &amp; agriculture}, volume = {13}, number = {1}, pages = {17-26}, doi = {10.2174/2212798412666220318162322}, pmid = {35307002}, issn = {2772-5758}, support = {2018/IF180896//DST-INSPIRE/ ; }, mesh = {Humans ; *Metabolic Syndrome/therapy ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/therapy ; *Cardiovascular Diseases ; Prebiotics ; }, abstract = {BACKGROUND: The balanced composition of the gut microbiota is essential for human health. The dysbiotic condition may develop various complex diseases. A metabolic syndrome is a group of biochemical and physiological abnormalities that can increase the risk of cardiovascular diseases, diabetes, and inflammatory diseases. It has become a serious concern worldwide because there is no acceptable medication to overcome this problem.<br><br>OBJECTIVE: This review aims to evaluate the relationship between gut microbiota and metabolic syndrome. The balance of gut microbiota relates to human health as well as diseases. Patents related to significant findings on probiotics, prebiotics, synbiotics, and fecal microbiota transplantation signify the importance of the proposed theme and provide promising therapeutic strategies to modulate the dysbiotic condition and reoccurrence of beneficial microbial species during metabolic syndromes. Screening of patents-related databases can be worth full to track new technology. Therefore, some selected recent patents related to gut microbiota and associated therapies have been discussed in the present manuscript.<br><br>CONCLUSION: Under the existing situation, the role of gastrointestinal microbiota as a therapeutic agent is becoming more utilized for treating human health issues and various metabolic syndromes including obesity, diabetes, and cardiovascular diseases. Understanding gut dysbiosis and associated complex interactions between microbes and hosts would be effective for designing future therapeutic interventions for metabolic syndrome. Our detailed patent analysis reflects that gut dysbiosis has a prominent role in metabolic syndromes and dietary therapeutic strategies can improve health by modulating the human microbiota, their metabolites ad stability.}, }
@article {pmid35305720, year = {2022}, author = {Giles, J and Roberts, A}, title = {Clostridioides difficile: Current overview and future perspectives.}, journal = {Advances in protein chemistry and structural biology}, volume = {129}, number = {}, pages = {215-245}, doi = {10.1016/bs.apcsb.2021.11.003}, pmid = {35305720}, issn = {1876-1631}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/drug therapy ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {The most common world-wide cause of antibiotic-associated infectious diarrhea and colitis is the toxin producing bacterium, Clostridioides difficile (C. difficile). Here we review the background and characteristics of the bacterium and the toxins produced together with the epidemiology and the complex pathogenesis that leads to a broad clinical spectrum of disease. The review describes the difficulties faced in obtaining a quick and accurate diagnosis despite the range of sensitive and specific diagnostic tools available. We also discuss the problem of disease recurrence and the importance of disease prevention. The high rates of infection recurrence mean that treatment strategies are constantly under review and we outline the diverse treatment options that are currently in use and explore the emerging treatment options of pulsed antibiotic use, microbial replacement therapies and the use of monoclonal antibodies. We summarize the future direction of treatment strategies which include the development of novel antibiotics, the administration of oral polyclonal antibody formulations, the use of vaccines, the administration of competitive non-toxigenic spores and the neutralization of antibiotics at the microbiota level. Future successful treatments will likely involve a combination of therapies to provide the most effective and robust approach to C. difficile management.}, }
@article {pmid35303781, year = {2022}, author = {Wei, Y and Peng, S and Lian, C and Kang, Q and Chen, J}, title = {Anorexia nervosa and gut microbiome: implications for weight change and novel treatments.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {16}, number = {4}, pages = {321-332}, doi = {10.1080/17474124.2022.2056017}, pmid = {35303781}, issn = {1747-4132}, mesh = {*Anorexia Nervosa/therapy ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {INTRODUCTION: Host-microbiota interactions may be involved in many physical and psychological functions ranging from the digestion of food, maintenance of immune homeostasis, to the regulation of mood and cognition. Microbiome dysbiosis has been consistently described in many diseases. The pathogenesis and weight regulation mechanism in anorexia nervosa (AN) also seem to be implicated in the dynamic bidirectional adjustment of the microbiota-gut-brain axis. This review aims at elucidating this relationship.<br><br>AREA COVERED: This review starts with a description of pathogenic gut-brain pathways. Next, we focus on the latest research on the associations between gut microbiota and weight change in the condition of AN. The strategies to alter the intestinal microbiome for the treatment of this disorder are discussed, including dietary, probiotics, prebiotics, synbiotics, and fecal microbiota transplantation.<br><br>EXPERT OPINION: Gut microbiome is inextricably linked to AN. It may regulate weight gain in the process of refeeding via the microbiota-gut-brain axis, while the specific mechanism has yet to be clearly established. In the future, a better understanding of gut microbiome could have implications for developing microbiome-based prevention, diagnostics and therapies.}, }
@article {pmid35302268, year = {2022}, author = {El-Salhy, M and Mazzawi, T and Hausken, T and Hatlebakk, JG}, title = {Irritable bowel syndrome patients who are not likely to respond to fecal microbiota transplantation.}, journal = {Neurogastroenterology and motility}, volume = {34}, number = {9}, pages = {e14353}, pmid = {35302268}, issn = {1365-2982}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome ; Male ; Quality of Life ; RNA, Ribosomal, 16S ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) interventions have recently been advocated to not succeed in every irritable bowel syndrome (IBS) patient, since the outcome of FMT varies with the IBS subset. This study investigated the factors potentially affecting FMT response using the same patient cohort used in our previous study.<br><br>METHODS: This study included 109 patients who received allogenic FMT. Patients completed five questionnaires that assessed their symptoms and quality of life at baseline and at 2&#xa0;weeks, 1&#xa0;month, and 3&#xa0;months after FMT. Patients also provided fecal samples at baseline and 1&#xa0;month after FMT. The fecal bacterial profile and dysbiosis index (DI) were determined using 16S rRNA gene PCR DNA amplification covering variable genes V3-V9. Response to FMT was defined as a decrease of &#x2265;50 points in the total IBS-SSS score after FMT.<br><br>RESULTS: An IBS patient's response or nonresponse to FMT was not determined by age, IBS duration, IBS subtype, IBS symptoms, fatigue, quality of life, or DI. There were more male nonresponders than responders, and the fluorescence signals of Alistipes were lower in nonresponders than in responders.<br><br>CONCLUSIONS: We concluded that IBS patients who are male and/or have low fecal Alistipes levels are most likely to not respond to FMT treatment. Whether low fecal Alistipes levels could be used as a marker for predicting the outcome of FMT remains to be determined. www.<br><br>CLINICALTRIALS: gov (NCT03822299).}, }
@article {pmid35301705, year = {2022}, author = {Pan, Z and Hu, Y and Huang, Z and Han, N and Li, Y and Zhuang, X and Yin, J and Peng, H and Gao, Q and Zhang, W and Huang, Y and Cui, Y and Bi, Y and Xu, ZZ and Yang, R}, title = {Alterations in gut microbiota and metabolites associated with altitude-induced cardiac hypertrophy in rats during hypobaric hypoxia challenge.}, journal = {Science China. Life sciences}, volume = {65}, number = {10}, pages = {2093-2113}, pmid = {35301705}, issn = {1869-1889}, mesh = {Altitude ; Animals ; Bile Acids and Salts ; Cardiomegaly ; Fatty Acids, Volatile ; Feces/microbiology ; *Gastrointestinal Microbiome ; Hypoxia/metabolism ; Propionates ; Rats ; }, abstract = {The gut microbiota is involved in host responses to high altitude. However, the dynamics of intestinal microecology and their association with altitude-related illness are poorly understood. Here, we used a rat model of hypobaric hypoxia challenge to mimic plateau exposure and monitored the gut microbiome, short-chain fatty acids (SCFAs), and bile acids (BAs) over 28 d. We identified weight loss, polycythemia, and pathological cardiac hypertrophy in hypoxic rats, accompanied by a large compositional shift in the gut microbiota, which is mainly driven by the bacterial families of Prevotellaceae, Porphyromonadaceae, and Streptococcaceae. The aberrant gut microbiota was characterized by increased abundance of the Parabacteroides, Alistipes, and Lactococcus genera and a larger Bacteroides to Prevotella ratio. Trans-omics analyses showed that the gut microbiome was significantly correlated with the metabolic abnormalities of SCFAs and BAs in feces, suggesting an interaction network remodeling of the microbiome-metabolome after the hypobaric hypoxia challenge. Interestingly, the transplantation of fecal microbiota significantly increased the diversity of the gut microbiota, partially inhibited the increased abundance of the Bacteroides and Alistipes genera, restored the decrease of plasma propionate, and moderately ameliorated cardiac hypertrophy in hypoxic rats. Our results provide an insight into the longitudinal changes in intestinal microecology during the hypobaric hypoxia challenge. Abnormalities in the gut microbiota and microbial metabolites contribute to the development of high-altitude heart disease in rats.}, }
@article {pmid35300220, year = {2022}, author = {Hu, C and Patil, Y and Gong, D and Yu, T and Li, J and Wu, L and Liu, X and Yu, Z and Ma, X and Yong, Y and Chen, J and Gooneratne, R and Ju, X}, title = {Heat Stress-Induced Dysbiosis of Porcine Colon Microbiota Plays a Role in Intestinal Damage: A Fecal Microbiota Profile.}, journal = {Frontiers in veterinary science}, volume = {9}, number = {}, pages = {686902}, pmid = {35300220}, issn = {2297-1769}, abstract = {The pathological mechanisms of gastrointestinal disorders, including inflammatory bowel disease (IBD), in pigs are poorly understood. We report the induction of intestinal inflammation in heat-stressed (HS) pigs, fecal microbiota transplantation from pigs to mice, and explain the role of microorganisms in IBD. 24 adult pigs were subjected to HS (34 ± 1 °C; 75-85% relative humidity for 24h) while 24 control pigs (CP) were kept at 25 ± 3°C and the same humidity. Pigs were sacrificed on days 1, 7, 14, 21. Colonic content microbiome analyses were conducted. Pseudo-germ-free mice were fed by gavage with fecal microbiota from HS-pigs and CP to induce pig-like responses in mice. From 7 d, HS-pigs exhibited fever and diarrhea, and significantly lower colonic mucosal thickness, crypt depth/width, and goblet cell number. Compared with each control group, the concentration of cortisol in the peripheral blood of HS pigs gradually increased, significantly so on days 7, 14, and 21 (P < 0.01). While the concentration of LPS in HS pigs' peripheral blood was significantly higher on days 7, 14 (P < 0.01), and 21 (P < 0.05) compared with that of the control group. The colonic microbiome composition of HS-pigs was different to that of CP. By day 14, opportunistic pathogens (e.g., Campylobacterales) had increased in HS-pigs. The composition of the colonic microbiome in mice administered feces from HS-pigs was different from those receiving CP feces. Bacteroides were significantly diminished, Akkermansia were significantly increased, and intestinal damage and goblet cell numbers were higher in mice that received HS-pig feces. Moreover, we verified the relevance of differences in the microbiota of the colon among treatments. Heat stress promotes changes in gut microbiome composition, which can affect the colonic microbial structure of mice through fecal microbiota transplantation; the molecular mechanisms require further investigation. This study enhanced our understanding of stress-induced inflammation in the colon and the increase in diarrhea in mammals subjected to prolonged HS. Our results provide useful information for preventing or ameliorating deficits in pig production caused by prolonged exposure to high temperatures.}, }
@article {pmid35299780, year = {2022}, author = {Liu, CK and Seo, J and Pravodelov, V and Frazier, S and Guy, M and Concilio, K and Lau-Ng, R and Brandeis, G and Watson, J and van der Velde, J and Olesen, SW and Budree, S and Njenga, M and Kassam, Z and Osman, M}, title = {Pilot study of autologous fecal microbiota transplants in nursing home residents: Feasibility and safety.}, journal = {Contemporary clinical trials communications}, volume = {27}, number = {}, pages = {100906}, pmid = {35299780}, issn = {2451-8654}, abstract = {INTRODUCTION: Antibiotic resistant bacterial infections (ARBIs) are extremely common in nursing home residents. These infections typically occur after a course of antibiotics, which eradicate both pathological and beneficial organisms. The eradication of beneficial organisms likely facilitates subsequent ARBIs. Autologous fecal microbiota transplant (aFMT) has been proposed as a potential treatment to reduce ARBIs in nursing home residents. Our objective was to determine the feasibility and safety of aFMT in a nursing home population.<br><br>METHODS: Pilot clinical trial. We evaluated feasibility as total number of stool samples collected for aFMT production and safety as the number and relatedness of serious (SAE) and non-serious adverse events (AE).<br><br>RESULTS: We screened 468 nursing home residents aged &#x2265;18 years for eligibility; 67 enrolled, distributed among three nursing homes. Participants were 62.7% female and 35.8% Black. Mean age was 82.2&#xa0;&#xb1;&#xa0;8.5 years. Thirty-three participants underwent successful stool collection. Seven participants received antibiotics; four participants underwent aFMT. There were 40 SAEs (17 deaths) and 11 AEs. In the aFMT group, there were 3 SAEs (2 deaths) and 10 AEs. All SAEs and AEs were judged unrelated to the study intervention.<br><br>CONCLUSIONS: In this pilot study of aFMT in nursing home residents, less than half were able to provide adequate stool samples for aFMT. There were no related SAEs or AEs during the study. In sum, we conclude aFMT has limited feasibility in a nursing home population due to logistic and technical challenges but is likely safe.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03061097.}, }
@article {pmid35298520, year = {2022}, author = {Groenewegen, B and van Lingen, E and Ooijevaar, RE and Wessels, E and Feltkamp, MCW and Boeije-Koppenol, E and Verspaget, HW and Kuijper, EJ and van Prehn, J and Keller, JJ and Terveer, EM and , }, title = {How to prepare stool banks for an appropriate response to the ongoing COVID-19 pandemic: Experiences in the Netherlands and a retrospective comparative cohort study for faecal microbiota transplantation.}, journal = {PloS one}, volume = {17}, number = {3}, pages = {e0265426}, pmid = {35298520}, issn = {1932-6203}, mesh = {Aged ; COVID-19/epidemiology/*prevention &amp; control/transmission ; Clostridium Infections/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*virology ; Female ; Humans ; Male ; Netherlands/epidemiology ; Retrospective Studies ; SARS-CoV-2 ; *Tissue Banks ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an efficacious treatment for patients with recurrent Clostridioides difficile infections (rCDI). Stool banks facilitate FMT by providing screened faecal suspensions from highly selected healthy donors. Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic and the potential risk of SARS coronavirus-2 (SARS-CoV-2) transmission via FMT, many stool banks were forced to temporarily halt and adjust donor activities.<br><br>GOAL: The evaluation of a strategy to effectively continue stool banking activities during the ongoing COVID-19 pandemic.<br><br>STUDY: To restart our stool banking activities after an initial halt, we implemented periodic SARS-CoV-2 screening in donor faeces and serum, and frequent donor assessment for COVID-19 related symptoms. FMT donor and recipient data obtained before (2016-2019) and during the COVID-19 pandemic (March 2020-August 2021) were compared to assess stool banking efficacy.<br><br>RESULTS: Two out of ten donors developed COVID-19. No differences during versus before the COVID-19 pandemic were observed in the number of approved faeces donations (14 vs 22/month, p = 0.06), FMT requests for rCDI (3.9 vs 4.3/month, p = 0.6); rCDI patients eligible for FMT (80.6% vs 73.3%, p = 0.2); rCDI cure rate (90.3% vs 89.2%, p = 0.9); CDI-free survival (p = 0.7); the number of non-rCDI patients treated with FMT (0.5/month vs 0.4/month), and the number of possibly FMT related adverse events (9.5% vs 7.8%, p = 0.7). Two FMTs for rCDI were delayed due to COVID-19.<br><br>CONCLUSIONS: There is a continued need for FMT treatment of rCDI during the COVID-19 pandemic. Appropriate donor screening and SARS-CoV-2 infection prevention measures can be implemented in existing protocols without increasing the burden for donors, and allow safe, effective and efficient FMT during the ongoing COVID-19 pandemic. Stool banks should evaluate their SARS-CoV-2 donor screening protocols for long-term sustainability and efficacy, and share their experiences to help the utilisation, standardisation and improvement of stool banks worldwide.}, }
@article {pmid35297473, year = {2022}, author = {Nivet, C and Duhalde, V and Beaurain, M and Delobel, P and Quelven, I and Alric, L}, title = {Fecal Microbiota Transplantation for Refractory Clostridioides Difficile Infection Is Effective and Well Tolerated Even in Very Old Subjects: A Real-Life Study.}, journal = {The journal of nutrition, health &amp; aging}, volume = {26}, number = {3}, pages = {290-296}, pmid = {35297473}, issn = {1760-4788}, mesh = {Aged ; *Clostridioides difficile ; *Clostridium Infections/drug therapy/etiology ; Cohort Studies ; Fecal Microbiota Transplantation/adverse effects ; Humans ; Quality of Life ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is an innovative therapy indicated for the treatment of recurrent Clostridioides difficile infections. Although CDI and its complications are more common in very old patients (≥80 years) due to their comorbidities, frailty and senescence of the immune system, limited data are available for this older patient population.<br><br>DESIGN: This was a single-center, real-life cohort study with retrospective outcome data registration, conducted at Toulouse, France.<br><br>SETTING AND PARTICIPANTS: Older people group was compared to the control group aged 18-79 years.<br><br>MEASUREMENTS: The primary outcome was overall survival at 52 weeks for &#x2265;80 years patients compared to the control group after FMT. Recurrence-free survival at 52 weeks and, the occurrence of adverse events in the short and long term were the secondary endpoints.<br><br>RESULTS: A total of 58 patients were included, 19 were aged &#x2265;80 years and 39 were aged 18-79 years. Overall survival at 52 weeks after FMT of the very old patients was not different from the control group (78.9% versus 89.7%, p= 0.29). Recurrence-free survival of CDI was not different between groups, with 94.3% in the 18-79-group versus 86.9% in the &#x2265;80 group (p=0.44). The occurrence of short- or long-term adverse events was not statistically different between the two groups (36.8% vs 41%, p=0.45).<br><br>CONCLUSIONS: FMT is effective and well-tolerated in very old frail patients. This treatment brings a rapid benefit and limits the loss of functions. It also favors their maintenance at home or in a non-medical institution dedicated to dependent subjects and improves their quality of life.}, }
@article {pmid35297188, year = {2022}, author = {Ishibashi, R and Furusawa, Y and Honda, H and Watanabe, Y and Fujisaka, S and Nishikawa, M and Ikushiro, S and Kurihara, S and Tabuchi, Y and Tobe, K and Takatsu, K and Nagai, Y}, title = {Isoliquiritigenin Attenuates Adipose Tissue Inflammation and Metabolic Syndrome by Modifying Gut Bacteria Composition in Mice.}, journal = {Molecular nutrition &amp; food research}, volume = {66}, number = {10}, pages = {e2101119}, doi = {10.1002/mnfr.202101119}, pmid = {35297188}, issn = {1613-4133}, mesh = {Adipose Tissue/metabolism ; Animals ; Anti-Inflammatory Agents/pharmacology ; Bacteria ; Chalcones ; Diet, High-Fat/adverse effects ; Glucose/metabolism ; Inflammation/metabolism ; *Insulin Resistance ; *Metabolic Syndrome/drug therapy/metabolism ; Mice ; Mice, Inbred C57BL ; }, abstract = {SCOPE: Isoliquiritigenin (ILG) has been reported to attenuate adipose tissue inflammation and metabolic disorder; however, the underlying mechanisms remain to be elucidated. The aim of this study is to elucidate whether ILG shows the anti-inflammatory and antimetabolic syndrome effects through gut microbiota modification.<br><br>METHODS AND RESULTS: Mice are fed a high-fat diet (HFD) with or without ILG for up to 12 weeks. The effect of ILG on body weight, blood glucose level, adipose tissue inflammation, gut barrier function, and gut microbiota composition are investigated. ILG supplementation alleviates HFD-induced obesity, glucose tolerance, and insulin resistance and suppresses inflammatory gene expression in epididymal white adipose tissue (eWAT). Moreover, ILG supplementation modifies gut bacterial composition by increasing the abundance of antimetabolic disease-associated species (e.g., Parabacteroides goldsteinii and Akkemansia muciniphila) and up-regulated genes associated with gut barrier function. Fecal microbiome transplantation (FMT) from ILG-fed donors counteract HFD-induced body and eWAT weight changes, inflammation-related gene expression, glucose tolerance, and insulin resistance, thereby suggesting that ILG-responsive gut bacteria exerts anti-inflammatory and antimetabolic syndrome effects.<br><br>CONCLUSION: Alterations in gut bacteria underly the beneficial effects of ILG against adipose tissue inflammation and metabolic disorders. ILG may be a promising prebiotic for the prevention and treatment of metabolic syndrome.}, }
@article {pmid35295757, year = {2022}, author = {Wu, J and Lv, L and Wang, C}, title = {Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {827395}, pmid = {35295757}, issn = {2235-2988}, mesh = {Adult ; Colonoscopy ; Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; *Irritable Bowel Syndrome/therapy ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Randomized controlled trials (RCTs) have examined the efficacy of fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) with inconsistent results. We performed a meta-analysis to assess both the short- and long-term efficacy of FMT in IBS.<br><br>METHODS: MEDLINE, EMBASE, and the Cochrane Central Register were searched through September 2021. RCTs recruiting adult patients with IBS that compared FMT with placebo with dichotomous data of response to therapy were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of symptom not improving after therapy. RR was also pooled for adverse events (AEs). Continuous data were calculated using a mean difference for IBS-Quality of Life (IBS-QoL). GRADE methodology was used to assess quality of evidence.<br><br>RESULTS: The search strategy generated 658 citations. Seven RCTs comprising 472 patients with IBS were included. FMT was not associated with a significant improvement in global symptom in IBS at 12 weeks in comparison with placebo (RR 0.75, 95% CI 0.43-1.31) with high heterogeneity between studies (I[2] 87%). Subgroup analyses showed that FMT was superior to placebo when administered via colonoscopy or gastroscope (RR 0.70, 95% CI 0.51-0.96; RR 0.37, 95% CI 0.14-0.99, respectively, while FMT was inferior to placebo when administered via oral capsules (RR 1.88, 95% CI 1.06-3.35). FMT induced a significant improvement in IBS-QoL compared to placebo (mean difference 9.39, 95% CI 3.86-14.91) at 12 weeks. No significant difference in the total number of AEs was observed between FMT and placebo (RR 1.20, 95% CI 0.59-2.47). FMT did not significantly improve global symptom in IBS at 1-year follow-up compared with placebo (RR 0.90, 95% CI 0.72-1.12). The GRADE quality evidence to support recommending FMT in IBS was very low.<br><br>CONCLUSION: IBS patients may benefit from FMT when administered via colonoscopy or gastroscope. FMT may improve the quality of life of IBS. The long-term use of FMT in IBS warrants further investigation. There is very-low-quality evidence to support recommending FMT in IBS.}, }
@article {pmid35292746, year = {2022}, author = {Hosokawa, M and Endoh, T and Kamata, K and Arikawa, K and Nishikawa, Y and Kogawa, M and Saeki, T and Yoda, T and Takeyama, H}, title = {Strain-level profiling of viable microbial community by selective single-cell genome sequencing.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {4443}, pmid = {35292746}, issn = {2045-2322}, mesh = {Bacteria/genetics ; Escherichia coli/genetics ; Fecal Microbiota Transplantation ; Feces/microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Culture-independent analysis with high-throughput sequencing has been widely used to characterize bacterial communities. However, signals derived from non-viable bacteria and non-cell DNA may inhibit its characterization. Here, we present a method for viable bacteria-targeted single-cell genome sequencing, called PMA-SAG-gel, to obtain comprehensive whole-genome sequences of surviving uncultured bacteria from microbial communities. PMA-SAG-gel uses gel matrixes that enable sequential enzymatic reactions for cell lysis and genome amplification of viable single cells from the microbial communities. PMA-SAG-gel removed the single-amplified genomes (SAGs) derived from dead bacteria and enabled selective sequencing of viable bacteria in the model samples of Escherichia coli and Bacillus subtilis. Next, we demonstrated the recovery of near-complete SAGs of eight oxygen-tolerant bacteria, including Bacteroides spp. and Phocaeicola spp., from 1331 human feces SAGs. We found the presence of two different strains in each species and identified their specific genes to investigate the metabolic functions. The survival profile of an entire population at the strain level will provide the information for understanding the characteristics of the surviving bacteria under the specific environments or sample processing and insights for quality assessment of live bacterial products or fecal microbiota transplantation and for understanding the effect of antimicrobial treatments.}, }
@article {pmid35292630, year = {2022}, author = {Daniel, N and Nachbar, RT and Tran, TTT and Ouellette, A and Varin, TV and Cotillard, A and Quinquis, L and Gagné, A and St-Pierre, P and Trottier, J and Marcotte, B and Poirel, M and Saccareau, M and Dubois, MJ and Joubert, P and Barbier, O and Koutnikova, H and Marette, A}, title = {Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {1343}, pmid = {35292630}, issn = {2041-1723}, support = {FDN-143247//CIHR/Canada ; }, mesh = {Animals ; *Diabetes Mellitus, Type 2/metabolism/prevention &amp; control ; Fermentation ; *Gastrointestinal Microbiome ; Hydroxy Acids/pharmacology ; Mice ; Mice, Obese ; Yogurt ; }, abstract = {Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota. We further show that yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters. These metabolites are generated upon milk fermentation and concentrated in yogurt. Remarkably, diet-induced obesity reduces plasma and tissue BCHA levels, and this is partly prevented by dietary yogurt intake. We further show that BCHA improve insulin action on glucose metabolism in liver and muscle cells, identifying BCHA as cell-autonomous metabolic regulators and potential mediators of yogurt's health effects.}, }
@article {pmid35291651, year = {2022}, author = {Bae, J and Park, K and Kim, YM}, title = {Commensal Microbiota and Cancer Immunotherapy: Harnessing Commensal Bacteria for Cancer Therapy.}, journal = {Immune network}, volume = {22}, number = {1}, pages = {e3}, pmid = {35291651}, issn = {1598-2629}, abstract = {Cancer is one of the leading causes of death worldwide and the number of cancer patients is expected to continuously increase in the future. Traditional cancer therapies focus on inhibiting cancer growth while largely ignoring the contribution of the immune system in eliminating cancer cells. Recently, better understanding of immunological mechanisms pertaining to cancer progress has led to development of several immunotherapies, which revolutionized cancer treatment. Nonetheless, only a small proportion of cancer patients respond to immunotherapy and maintain a durable response. Among multiple factors contributing to the variability of immunotherapy response rates, commensal microbiota inhabiting patients have been identified as one of the most critical factors determining the success of immunotherapy. The functional diversity of microbiota differentially affects the host immune system and controls the efficacy of immunotherapy in individual cancer patients. Moreover, clinical studies have demonstrated that changing the gut microbiota composition by fecal microbiota transplantation in patients who failed a previous immunotherapy converts them to responders of the same therapy. Consequently, both academic and industrial researchers are putting extensive efforts to identify and develop specific bacteria or bacteria mixtures for cancer immunotherapy. In this review, we will summarize the immunological roles of commensal microbiota in cancer treatment and give specific examples of bacteria that show anticancer effect when administered as a monotherapy or as an adjuvant agent for immunotherapy. We will also list ongoing clinical trials testing the anticancer effect of commensal bacteria.}, }
@article {pmid35288695, year = {2022}, author = {Smith, M and Dai, A and Ghilardi, G and Amelsberg, KV and Devlin, SM and Pajarillo, R and Slingerland, JB and Beghi, S and Herrera, PS and Giardina, P and Clurman, A and Dwomoh, E and Armijo, G and Gomes, ALC and Littmann, ER and Schluter, J and Fontana, E and Taur, Y and Park, JH and Palomba, ML and Halton, E and Ruiz, J and Jain, T and Pennisi, M and Afuye, AO and Perales, MA and Freyer, CW and Garfall, A and Gier, S and Nasta, S and Landsburg, D and Gerson, J and Svoboda, J and Cross, J and Chong, EA and Giralt, S and Gill, SI and Riviere, I and Porter, DL and Schuster, SJ and Sadelain, M and Frey, N and Brentjens, RJ and June, CH and Pamer, EG and Peled, JU and Facciabene, A and van den Brink, MRM and Ruella, M}, title = {Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy.}, journal = {Nature medicine}, volume = {28}, number = {4}, pages = {713-723}, pmid = {35288695}, issn = {1546-170X}, support = {R01 CA226983/CA/NCI NIH HHS/United States ; P01 CA214278/CA/NCI NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; R01 CA219871/CA/NCI NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; K99 CA212302/CA/NCI NIH HHS/United States ; K08 CA194256/CA/NCI NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; R00 CA212302/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; R01 CA206012/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; }, mesh = {Antigens, CD19 ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy, Adoptive/adverse effects ; *Neurotoxicity Syndromes/etiology ; Prospective Studies ; *Receptors, Chimeric Antigen ; Retrospective Studies ; }, abstract = {Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has led to unprecedented responses in patients with high-risk hematologic malignancies. However, up to 60% of patients still experience disease relapse and up to 80% of patients experience CAR-mediated toxicities, such as cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. We investigated the role of the intestinal microbiome on these outcomes in a multicenter study of patients with B cell lymphoma and leukemia. We found in a retrospective cohort (n = 228) that exposure to antibiotics, in particular piperacillin/tazobactam, meropenem and imipenem/cilastatin (P-I-M), in the 4 weeks before therapy was associated with worse survival and increased neurotoxicity. In stool samples from a prospective cohort of CAR T cell recipients (n = 48), the fecal microbiome was altered at baseline compared to healthy controls. Stool sample profiling by 16S ribosomal RNA and metagenomic shotgun sequencing revealed that clinical outcomes were associated with differences in specific bacterial taxa and metabolic pathways. Through both untargeted and hypothesis-driven analysis of 16S sequencing data, we identified species within the class Clostridia that were associated with day 100 complete response. We concluded that changes in the intestinal microbiome are associated with clinical outcomes after anti-CD19 CAR T cell therapy in patients with B cell malignancies.}, }
@article {pmid35288507, year = {2022}, author = {Li, H and Wang, Y and Zhao, C and Liu, J and Zhang, L and Li, A}, title = {Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion.}, journal = {Chinese medical journal}, volume = {135}, number = {6}, pages = {707-713}, pmid = {35288507}, issn = {2542-5641}, mesh = {Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Mice ; RNA, Ribosomal, 16S/genetics ; Serotonin ; *Tics ; *Tourette Syndrome/therapy ; }, abstract = {BACKGROUND: : Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.<br><br>METHODS: : TS mice model (TSMO) (n&#x200a;=&#x200a;80) were established with 3,3'-iminodipropionitrile, and 80 mice were used as controls. Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS, or were given probiotics. Fecal specimens were collected 3 weeks after FMT. 16S rRNA sequencing, behavioral observation, and serum serotonin (5-HT) assay were performed. Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov (KS) tests.<br><br>RESULTS: : A total of 18 discriminative microbial signatures (linear discriminant analysis score&#x200a;>&#x200a;3) that varied significantly between TS and healthy mice (CONH) were identified. A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed (P&#x200a; <&#x200a;0.05). Compared with non-transplanted TSMO, the symptoms of those transplanted with feces from CONH were alleviated (W&#x200a;=&#x200a;336, P&#x200a;=&#x200a;0.046). In the probiotic and FMT experiments, the serum 5-HT levels significantly increased in TSMO that received probiotics (KS&#x200a;=&#x200a;1.423, P&#x200a;=&#x200a;0.035) and in those transplanted with feces from CONH (W&#x200a;=&#x200a;336.5, P&#x200a;=&#x200a;0.046) compared with TSMO without transplantation.<br><br>CONCLUSIONS: : This study suggests that FMT may ameliorate TS by promoting 5-HT secretion, and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.}, }
@article {pmid35286970, year = {2022}, author = {Vellingiri, B and Aishwarya, SY and Benita Jancy, S and Sriram Abhishek, G and Winster Suresh Babu, H and Vijayakumar, P and Narayanasamy, A and Mariappan, S and Sangeetha, R and Valsala Gopalakrishnan, A and Parthasarathi, R and Iyer, M}, title = {An anxious relationship between Autism Spectrum Disorder and Gut Microbiota: A tangled chemistry?.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {99}, number = {}, pages = {169-189}, doi = {10.1016/j.jocn.2022.03.003}, pmid = {35286970}, issn = {1532-2653}, mesh = {Animals ; Anxiety ; *Autism Spectrum Disorder/therapy ; Brain-Gut Axis ; Dysbiosis/complications ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Autism spectrum disorder (ASD) is a serious multifactorial neurodevelopmental disorder often accompanied by strained social communication, repetitive behaviour, immune dysregulation, and gastrointestinal (GI) issues. Recent studies have recorded a link between dysbiosis in the gut microbiota (gm) and the primary stages of ASD. A bidirectional connection (also called microbiota-gut-brain-axis) exchanges information between the gut bacteria and central nervous system. When the homeostasis of the microenvironment of the gut is dysregulated, it causes oxidative stress, affecting neuronal cells and neurotransmitters, thereby causing neurodevelopmental disorders. Studies have confirmed a difference in the constitution of gut bacteria among ASD cases and their controls. Numerous studies on animal models of ASD have shown altered gm and its association with abnormal metabolite profile and altered behaviour phenotype. This process happens due to an abnormal metabolite production in gm, leading to changes in the immune system, especially in ASD. Hence, this review aims to question the current knowledge on gm dysbiosis and its related GI discomforts and ASD behavioural symptoms and shed light on the possible therapeutic approaches available to deal with this situation. Thereby, though it is understood that more research might be needed to prove an association or causal relationship between gm and ASD, therapy with the microbiome may also be considered as an effective strategy to combat this issue.}, }
@article {pmid35283312, year = {2022}, author = {Krutova, M and de Meij, TGJ and Fitzpatrick, F and Drew, RJ and Wilcox, MH and Kuijper, EJ}, title = {How to: Clostridioides difficile infection in children.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {8}, pages = {1085-1090}, doi = {10.1016/j.cmi.2022.03.001}, pmid = {35283312}, issn = {1469-0691}, mesh = {Aged ; Anti-Bacterial Agents/therapeutic use ; Child ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/epidemiology/therapy ; Fidaxomicin/therapeutic use ; Humans ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Clostridioides difficile infections (CDI) are traditionally attributed to an older adult patient group but children can also be affected. Although the causative pathogen is the same in both populations, the management of CDI may differ.<br><br>OBJECTIVES: To discuss the current literature on CDI in the paediatric population and to provide CDI diagnostics and treatment guidance.<br><br>SOURCES: The literature was drawn from a search of PubMed from January 2017 to July 2021.<br><br>CONTENT: In the paediatric population, laboratory diagnostics for CDI should preferably be combined with laboratory diagnostics for other gastrointestinal pathogens. Coinfections of CDI are also possible. Though the detection of toxigenic C.&#xa0;difficile using a molecular assay may simply reflect colonisation rather than infection, detection of C.&#xa0;difficile free toxins A/B in faeces is much more indicative of true infection. CDI in children below 2&#xa0;years of age and in the absence of risk factors is very difficult to diagnose and requires careful clinical judgement pending additional studies. Fidaxomicin has been shown to be superior to vancomycin with a sustained clinical response up to 30&#xa0;days after the end of CDI treatment in children. Metronidazole is less effective than vancomycin in adults and there are no supporting data for its use in children. In recurrent CDI, treatment should be adjusted according to the drug or drug regimen used for the treatment of a previous episode(s). In multiple recurrent CDI, faecal microbiota transplantation can be effective.<br><br>IMPLICATIONS: If CDI laboratory testing is indicated in children with diarrhoea, the likelihood of C.&#xa0;difficile colonisation and coinfection with other intestinal pathogens should be considered. The currently available data support a change in the treatment strategy of CDI in children.}, }
@article {pmid35279514, year = {2022}, author = {Xu, J and Liu, C and Shi, K and Sun, X and Song, C and Xu, K and Liu, Y}, title = {Atractyloside-A ameliorates spleen deficiency diarrhea by interfering with TLR4/MyD88/NF-κB signaling activation and regulating intestinal flora homeostasis.}, journal = {International immunopharmacology}, volume = {107}, number = {}, pages = {108679}, doi = {10.1016/j.intimp.2022.108679}, pmid = {35279514}, issn = {1878-1705}, mesh = {Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Atractyloside ; Diarrhea/drug therapy ; *Gastrointestinal Microbiome ; Homeostasis ; Mice ; Myeloid Differentiation Factor 88/genetics/metabolism ; *NF-kappa B/metabolism ; Signal Transduction ; Spleen/metabolism ; Toll-Like Receptor 4/genetics/metabolism ; }, abstract = {PURPOSE: Spleen deficiency diarrhea (SDD) is one of the most common types of diarrhea and is linked to intestinal barrier dysfunction and intestinal flora disorders. Atractyloside-A (AA) is one of the main components of Atractylodes Lancea(Thunb.) DC., which acts on the gastrointestinal tract and has therapeutic effects on diarrhea. Folium sennae is a medicinal plant inducing diarrhea; thus, it is one of the effective methods to obtain a diarrhea model. However, the mechanism of action of AA in the treatment of SDD induced by Folium sennae is unclear.<br><br>METHODS: The intestinal thrapeutic effect of AA on SDD in mice was evaluated by colon pathology. RNA sequencing (RNA-seq) was used to analyze the colonic transcriptome profiles. In addition, 16S rDNA sequencing and fecal microbiota transplantation (FMT) were carried out to verify the role of AA in the regulation of the intestinal flora.<br><br>RESULTS: The findings revealed that AA alleviated SDD by ameliorating the pathological symptoms while suppressing intestinal inflammatory responses through the TLR4/MyD88/NF-kB signaling and reversing the impairment of mucin synthesis. Furthermore, AA improved the integrity of the intestinal barrier. RNA-seq identified 436 common DEGs out of 1033 DEGs between SDD and AA, and 1933 DEGs between SDD and Ctrl, which are highly enriched in the NF-&#x3ba;B and TNF pathways. Moreover, AA altered the composition of the intestinal flora and FMT reduced SDD.<br><br>CONCLUSION: AA exerted a therapeutic effect on SDD through the regulation of the intestinal flora and the inflammation by interfering with the TLR4/MyD88/NF-&#x3ba;B signaling pathway.}, }
@article {pmid35279084, year = {2022}, author = {Orenstein, R and Dubberke, ER and Khanna, S and Lee, CH and Yoho, D and Johnson, S and Hecht, G and DuPont, HL and Gerding, DN and Blount, KF and Mische, S and Harvey, A}, title = {Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial.}, journal = {BMC infectious diseases}, volume = {22}, number = {1}, pages = {245}, pmid = {35279084}, issn = {1471-2334}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; *Microbiota ; Neoplasm Recurrence, Local ; Prospective Studies ; Retrospective Studies ; }, abstract = {BACKGROUND: Effective treatment options for recurrent Clostridioides difficile infection (rCDI) are limited, with high recurrence rates associated with the current standard of care. Herein we report results from an open-label Phase 2 trial to evaluate the safety, efficacy, and durability of RBX2660-a standardized microbiota-based investigational live biotherapeutic-and a closely-matched historical control cohort.<br><br>METHODS: This prospective, multicenter, open-label Phase 2 study enrolled patients who had experienced either&#x2009;&#x2265;&#x2009;2 recurrences of CDI, treated by standard-of-care antibiotic therapy, after a primary CDI episode, or&#x2009;&#x2265;&#x2009;2 episodes of severe CDI requiring hospitalization. Participants received up to 2 doses of RBX2660 rectally administered with doses 7&#xa0;days apart. Treatment success was defined as the absence of CDI diarrhea without the need for retreatment for 8&#xa0;weeks after completing study treatment. A historical control group with matched inclusion and exclusion criteria was identified from a retrospective chart review of participants treated with standard-of-care antibiotics for recurrent CDI who matched key criteria for the study. The primary objective was to compare treatment success of RBX2660 to the historical control group. A key secondary outcome was the safety profile of RBX2660, including adverse events and CDI occurrence through 24&#xa0;months after treatment. In addition, fecal samples from RBX2660-treated participants were sequenced to evaluate microbiome composition and functional changes from before to after treatment.<br><br>RESULTS: In this Phase 2 open-label clinical trial, RBX2660 demonstrated a 78.9% (112/142) treatment success rate compared to a 30.7% (23/75) for the historical control group (p&#x2009;<&#x2009;0.0001; Chi-square test). Post-hoc analysis indicated that 91% (88/97) of evaluable RBX2660 responders remained CDI occurrence-free to 24&#xa0;months after treatment demonstrating durability. RBX2660 was well-tolerated with mostly mild to moderate adverse events. The composition and diversity of RBX2660 responders' fecal microbiome significantly changed from before to after treatment to become more similar to RBX2660, and these changes were durable to 24&#xa0;months after treatment.<br><br>CONCLUSIONS: In this Phase 2 trial, RBX2660 was safe and effective for reducing rCDI recurrence as compared to a historical control group. Microbiome changes are consistent with restorative changes implicated in resisting C. difficile recurrence. Clinical Trials Registration NCT02589847 (10/28/2015).}, }
@article {pmid35278396, year = {2022}, author = {Haifer, C and Paramsothy, S and Kaakoush, NO and Leong, RW}, title = {Oral faecal microbiota transplantation in ulcerative colitis - Authors' reply.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {4}, pages = {286-287}, doi = {10.1016/S2468-1253(22)00045-0}, pmid = {35278396}, issn = {2468-1253}, mesh = {*Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid35278395, year = {2022}, author = {Yuan, TY and Rajesh, R and Tan, M}, title = {Oral faecal microbiota transplantation in ulcerative colitis.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {4}, pages = {286}, doi = {10.1016/S2468-1253(21)00469-6}, pmid = {35278395}, issn = {2468-1253}, mesh = {*Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid35278334, year = {2023}, author = {Donoso, F and Cryan, JF and Olavarría-Ramírez, L and Nolan, YM and Clarke, G}, title = {Inflammation, Lifestyle Factors, and the Microbiome-Gut-Brain Axis: Relevance to Depression and Antidepressant Action.}, journal = {Clinical pharmacology and therapeutics}, volume = {113}, number = {2}, pages = {246-259}, pmid = {35278334}, issn = {1532-6535}, mesh = {Humans ; *Brain-Gut Axis ; *Depression/therapy ; Antidepressive Agents/therapeutic use ; Inflammation ; Life Style ; }, abstract = {Depression is considered a major public health concern, where existing pharmacological treatments are not equally effective across all patients. The pathogenesis of depression involves the interaction of complex biological components, such as the immune system and the microbiota-gut-brain axis. Adjunctive lifestyle-oriented approaches for depression, including physical exercise and special diets are promising therapeutic options when combined with traditional antidepressants. However, the mechanisms of action of these strategies are incompletely understood. Accumulating evidence suggests that physical exercise and specific dietary regimens can modulate both the immune system and gut microbiota composition. Here, we review the current information about the strategies to alleviate depression and their crosstalk with both inflammatory mechanisms and the gut microbiome. We further discuss the role of the microbiota-gut-brain axis as a possible mediator for the adjunctive therapies for depression through inflammatory mechanisms. Finally, we review existing and future adjunctive strategies to manipulate the gut microbiota with potential use for depression, including physical exercise, dietary interventions, prebiotics/probiotics, and fecal microbiota transplantation.}, }
@article {pmid35277453, year = {2022}, author = {Ting, NL and Lau, HC and Yu, J}, title = {Cancer pharmacomicrobiomics: targeting microbiota to optimise cancer therapy outcomes.}, journal = {Gut}, volume = {71}, number = {7}, pages = {1412-1425}, pmid = {35277453}, issn = {1468-3288}, mesh = {Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Humans ; Immunotherapy ; *Microbiota ; *Neoplasms ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {Despite the promising advances in novel cancer therapy such as immune checkpoint inhibitors (ICIs), limitations including therapeutic resistance and toxicity remain. In recent years, the relationship between gut microbiota and cancer has been extensively studied. Accumulating evidence reveals the role of microbiota in defining cancer therapeutic efficacy and toxicity. Unlike host genetics, microbiota can be easily modified via multiple strategies, including faecal microbiota transplantation (FMT), probiotics and antibiotics. Preclinical studies have identified the mechanisms on how microbes influence cancer treatment outcomes. Clinical trials have also demonstrated the potential of microbiota modulation in cancer treatments. Herein, we review the mechanistic insights of gut microbial interactions with chemotherapy and ICIs, particularly focusing on the interplay between gut bacteria and the pharmacokinetics (eg, metabolism, enzymatic degradation) or pharmacodynamics (eg, immunomodulation) of cancer treatment. The translational potential of basic findings in clinical settings is then explored, including using microbes as predictive biomarkers and microbial modulation by antibiotics, probiotics, prebiotics, dietary modulations and FMT. We further discuss the current limitations of gut microbiota modulation in patients with cancer and suggest essential directions for future study. In the era of personalised medicine, it is crucial to understand the microbiota and its interactions with cancer. Manipulating the gut microbiota to augment cancer therapeutic responses can provide new insights into cancer treatment.}, }
@article {pmid35277036, year = {2022}, author = {Upreti, D and Ishiguro, S and Robben, N and Nakashima, A and Suzuki, K and Comer, J and Tamura, M}, title = {Oral Administration of Water Extract from Euglena gracilis Alters the Intestinal Microbiota and Prevents Lung Carcinoma Growth in Mice.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, pmid = {35277036}, issn = {2072-6643}, support = {N/A//Euglena Research Fund/ ; 2018 CVM-SMILE//Kansas State University/ ; P20 GM103418/GM/NIGMS NIH HHS/United States ; DMR-1945589//National Science Foundation/ ; 2020 JCRC-CRA//Kansas State University/ ; }, mesh = {Administration, Oral ; Animals ; *Carcinoma ; *Euglena gracilis ; *Gastrointestinal Microbiome ; Lung ; *Lung Neoplasms/prevention &amp; control ; Mice ; Water/pharmacology ; }, abstract = {The antitumor effects of a partially purified water extract from Euglena gracilis (EWE) and EWE treated by boiling (bEWE) were evaluated using orthotopic lung cancer syngeneic mouse models with Lewis lung carcinoma (LLC) cells. Daily oral administration of either EWE or bEWE started three weeks prior to the inoculation of LLC cells significantly attenuated tumor growth as compared to the phosphate buffered saline (PBS) control, and the attenuation was further enhanced by bEWE. The intestinal microbiota compositions in both extract-treated groups were more diverse than that in the PBS group. Particularly, a decrease in the ratio of Firmicutes to Bacteroidetes and significant increases in Akkermansia and Muribaculum were observed in two types of EWE-treated groups. Fecal microbiota transplantation (FMT) using bEWE-treated mouse feces attenuated tumor growth to an extent equivalent to bEWE treatment, while tumor growth attenuation by bEWE was abolished by treatment with an antibiotic cocktail. These studies strongly suggest that daily oral administration of partially purified water extracts from Euglena gracilis attenuates lung carcinoma growth via the alteration of the intestinal microbiota.}, }
@article {pmid35277027, year = {2022}, author = {Varesi, A and Pierella, E and Romeo, M and Piccini, GB and Alfano, C and Bjørklund, G and Oppong, A and Ricevuti, G and Esposito, C and Chirumbolo, S and Pascale, A}, title = {The Potential Role of Gut Microbiota in Alzheimer's Disease: From Diagnosis to Treatment.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, pmid = {35277027}, issn = {2072-6643}, mesh = {*Alzheimer Disease/diagnosis/therapy ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Prebiotics ; }, abstract = {Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer's Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease.}, }
@article {pmid35276971, year = {2022}, author = {Abujamel, TS and Al-Otaibi, NM and Abuaish, S and AlHarbi, RH and Assas, MB and Alzahrani, SA and Alotaibi, SM and El-Ansary, A and Aabed, K}, title = {Different Alterations in Gut Microbiota between Bifidobacterium longum and Fecal Microbiota Transplantation Treatments in Propionic Acid Rat Model of Autism.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, pmid = {35276971}, issn = {2072-6643}, support = {RGP-1441-0027//Deanship of Scientific Research, Princess Nora Bint Abdulrahman University/ ; }, mesh = {Animals ; *Autistic Disorder ; *Bifidobacterium longum/genetics ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Propionates ; RNA, Ribosomal, 16S/genetics ; Rats ; }, abstract = {Autism spectrum disorders (ASD) consist of a range of neurodevelopmental conditions accompanied by dysbiosis of gut microbiota. Therefore, a number of microbiota manipulation strategies were developed to restore their balance. However, a comprehensive comparison of the various methods on gut microbiota is still lacking. Here, we evaluated the effect of Bifidobacterium (BF) treatment and fecal microbiota transplantation (FT) on gut microbiota in a propionic acid (PPA) rat model of autism using 16S rRNA sequencing. Following PPA treatment, gut microbiota showed depletion of Bacteroidia and Akkermansia accompanied by a concomitant increase of Streptococcus, Lachnospiraceae, and Paraeggerthella. The dysbiosis was predicted to cause increased levels of porphyrin metabolism and impairments of acyl-CoA thioesterase and ubiquinone biosynthesis. On the contrary, BF and FT treatments resulted in a distinct increase of Clostridium, Bifidobacterium, Marvinbryantia, Butyricicoccus, and Dorea. The taxa in BF group positively correlated with vitamin B12 and flagella biosynthesis, while FT mainly enriched flagella biosynthesis. In contrast, BF and FT treatments negatively correlated with succinate biosynthesis, pyruvate metabolism, nitrogen metabolism, beta-Lactam resistance, and peptidoglycan biosynthesis. Therefore, the present study demonstrated that BF and FT treatments restored the PPA-induced dysbiosis in a treatment-specific manner.}, }
@article {pmid35276821, year = {2022}, author = {Prosperi, M and Santocchi, E and Guiducci, L and Frinzi, J and Morales, MA and Tancredi, R and Muratori, F and Calderoni, S}, title = {Interventions on Microbiota: Where Do We Stand on a Gut-Brain Link in Autism? A Systematic Review.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, pmid = {35276821}, issn = {2072-6643}, support = {2757130//Ricerca Corrente, and the "5 &#xd7; 1000" voluntary contributions, Italian Ministry of Health/ ; }, mesh = {*Autistic Disorder/therapy ; Brain ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Randomized Controlled Trials as Topic ; }, abstract = {The alteration of the microbiota-gut-brain axis has been recently recognized as a critical modulator of neuropsychiatric health and a possible factor in the etiopathogenesis of autism spectrum disorders (ASD). This systematic review offers practitioners an overview of the potential therapeutic options to modify dysbiosis, GI symptoms, and ASD severity by modulating the microbiota-gut-brain axis in ASD, taking into consideration limits and benefits from current findings. Comprehensive searches of PubMed, Scopus, the Web of Science Core Collection, and EMBASE were performed from 2000 to 2021, crossing terms referred to ASD and treatments acting on the microbiota-gut-brain axis. A total of 1769 publications were identified, of which 19 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Despite the encouraging findings, considering the variability of the treatments, the samples size, the duration of treatment, and the tools used to evaluate the outcome of the examined trials, these results are still partial. They do not allow to establish a conclusive beneficial effect of probiotics and other interventions on the symptoms of ASD. In particular, the optimal species, subspecies, and dosages have yet to be identified. Considering the heterogeneity of ASD, double-blind, randomized, controlled trials and treatment tailored to ASD characteristics and host-microbiota are recommended.}, }
@article {pmid35276080, year = {2022}, author = {Lam, S and Bai, X and Shkoporov, AN and Park, H and Wu, X and Lan, P and Zuo, T}, title = {Roles of the gut virome and mycobiome in faecal microbiota transplantation.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {5}, pages = {472-484}, doi = {10.1016/S2468-1253(21)00303-4}, pmid = {35276080}, issn = {2468-1253}, support = {220646/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; *Mycobiome ; Virome ; }, abstract = {Faecal microbiota transplantation (FMT) is an innovative approach to treat diseases that are associated with gut dysbiosis, by transferring a healthy stool microbiota to a recipient with disease. Beyond the bacteriome, the human gut also harbours diverse communities of viruses and fungi, collectively known as the virome and the mycobiome. The effect of the virome and the mycobiome on the success of FMT therapy has not been appreciated until recently. In this Review, we summarise the current literature on the effects of the gut virome and mycobiome on the treatment of various diseases with FMT. We discuss the beneficial effects and health concerns of viral and fungal transfer during FMT, and highlight the roles of bacteriophages and Candida species in FMT efficacy. We also summarise the intricate relationships between the gut virome, mycobiome, bacteriome, and host immunity underlying FMT effectiveness. Future efforts should be devoted to understanding the versatile roles and the therapeutic mechanisms of viral and fungal lineages, and their combinations, in different diseases. Harnessing the gut virome, mycobiome, and bacteriome in combination is a promising prospect for the future of FMT and microbiota-based therapies.}, }
@article {pmid35275989, year = {2022}, author = {Aby, ES and Vaughn, BP and Enns, EA and Rajasingham, R}, title = {Cost-effectiveness of Fecal Microbiota Transplantation for First Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {75}, number = {9}, pages = {1602-1609}, pmid = {35275989}, issn = {1537-6591}, support = {K25 AI118476/AI/NIAID NIH HHS/United States ; K23AI13885//National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Humans ; Fecal Microbiota Transplantation ; Cost-Benefit Analysis ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy ; Treatment Outcome ; Recurrence ; }, abstract = {BACKGROUND: Both the American College of Gastroenterology and the Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America 2021 Clostridioides difficile infection (CDI) guidelines recommend fecal microbiota transplantation (FMT) for persons with multiple recurrent CDI. Emerging data suggest that FMT may have high cure rates when used for first recurrent CDI. The aim of this study was to assess the cost-effectiveness of FMT for first recurrent CDI.<br><br>METHODS: We developed a Markov model to simulate a cohort of patients presenting with initial CDI infection. The model estimated the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the 2021 IDSA guidelines, with the additional option of FMT for first recurrent CDI. The model includes stratification by the severity of initial infection, estimates of cure, recurrence, and mortality. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).<br><br>RESULTS: When FMT is available for first recurrent CDI, the optimal cost-effective treatment strategy is fidaxomicin for initial nonsevere CDI, vancomycin for initial severe CDI, and FMT for first and subsequent recurrent CDI, with an ICER of $27 135/QALY. In probabilistic sensitivity analysis at a $100 000 cost-effectiveness threshold, FMT for first and subsequent CDI recurrence was cost-effective 90% of the time given parameter uncertainty.<br><br>CONCLUSIONS: FMT is a cost-effective strategy for first recurrent CDI. Prospective evaluation of FMT for first recurrent CDI is warranted to determine the efficacy and risk of recurrence.}, }
@article {pmid35273972, year = {2022}, author = {Ishikawa, D and Zhang, X and Nomura, K and Seki, N and Haraikawa, M and Haga, K and Shibuya, T and Kim, YG and Nagahara, A}, title = {A Randomized Placebo-Controlled Trial of Combination Therapy With Post-triple-antibiotic-therapy Fecal Microbiota Transplantation and Alginate for Ulcerative Colitis: Protocol.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {779205}, pmid = {35273972}, issn = {2296-858X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been widely performed for ulcerative colitis (UC) treatment at the clinical trial stage. Previous reports have used multiple FMT methods to enhance the colonization of healthy donor microbiota in the recipient's intestines. FMT following triple antibiotic therapy with amoxicillin, fosfomycin, and metronidazole (A-FMT) is not only effective but also requires only one FMT, which improves dysbiosis caused by reduced Bacteroidetes diversity in patients with UC. Alginate and its derivatives have the potential to induce the growth of intestinal bacteria including Bacteroides members and produce short-chain fatty acids (SCFAs), which are beneficial in regulating overactive autoimmunity. Our trial aims to investigate whether post-intervention with alginate, which can improve the intestinal environment, will enhance the therapeutic effect of A-FMT in UC and increase the long-term remission rate.<br><br>METHODS AND ANALYSIS: This trial is a double-blinded, randomized, placebo-controlled, parallel assignment trial. Patients with UC and fecal donation candidates will undergo strict screening before being involved in the trial. Eligible patients are randomly divided into two groups: one group will drink one bottle of alginate twice a day for 8 consecutive weeks after A-FMT, while the other group will take a placebo instead of the alginate drink. The primary endpoints are the changes in the Total Mayo Score at 8 weeks after study initiation and A-FMT from baseline. The secondary endpoint is the comparison of clinical features, microbiota, and metabolomic analysis before and after 8 weeks of study food intake. Changes at 6, 12, 18, and 24 months after A-FMT will be assessed. Finally, a subpopulation analysis of the relationship between patients and donors is an exploratory endpoint.<br><br>DISCUSSION: The FMT post-treatment used in this study is an oral alginate drink that is easily accepted by patients. If the regimen achieves the desired results, it can further improve the A-FMT regimen and provide evidence for clinical practice guidelines for UC.<br><br>CLINICAL TRIAL REGISTRATION: https://jrct.niph.go.jp/latest-detail/jRCTs031200103, identifier: jRCTs031200103.}, }
@article {pmid35273743, year = {2022}, author = {Triplett, J and Braddock, A and Roberts, E and Ellis, D and Chan, V}, title = {Identification of sleep fragmentation-induced gut microbiota alteration and prediction of functional impact in Sprague Dawley rats harboring microbiome derived from multiple human donors.}, journal = {Sleep science (Sao Paulo, Brazil)}, volume = {15}, number = {Spec 1}, pages = {07-19}, pmid = {35273743}, issn = {1984-0659}, abstract = {OBJECTIVES: Poor quality sleep, including sleep fragmentation (SF), can result in severe health consequences. Gut microbiota symbiotically coexist with the host, making essential contributions to overall well-being. In this study, the effects of both acute (6-day) and chronic (6-week) SF in a humanized rat model were examined to evaluate the impact of SF on this symbiotic relationship.<br><br>MATERIAL AND METHODS: Human fecal material was transplanted into antibiotic-treated, microbially depleted, Sprague Dawley rats. Animals were subjected to either acute or chronic SF and shifts to gut microbiota were investigated using 16S rRNA sequencing and predictive functional profiles were constructed with PICRUSt. We also investigated SF-induced intestinal microbial adhesion and penetration or increased microbial invasion of selected tissues and organs; as well as changes in crypt/villi architecture.<br><br>RESULTS: Microbiota profiling indicated that chronic, but not acute, SF significantly decreased the richness of alpha-diversity of distal ileum microbiota, and altered cecum and distal ileum beta-diversity; although both acute and chronic SF significantly changed select populations of microbiota in all three regions. Neither acute nor chronic SF induced changes to microbial adhesion, penetration, or invasion into intestinal tissues or nearby organs. Additionally, we found that chronic SF caused a reduction in villus height in the proximal colon.<br><br>DISCUSSION: Our study suggests that acute SF alters the gut microbiota in this humanized rat model, while chronic SF produces more pronounced changes to microbiota populations. This study identified potential microbiota targets for the prevention and/or intervention of the adverse effects of S F.}, }
@article {pmid35273587, year = {2022}, author = {Chen, Y and Song, S and Shu, A and Liu, L and Jiang, J and Jiang, M and Wu, Q and Xu, H and Sun, J}, title = {The Herb Pair Radix Rehmanniae and Cornus Officinalis Attenuated Testicular Damage in Mice With Diabetes Mellitus Through Butyric Acid/Glucagon-Like Peptide-1/Glucagon-Like Peptide-1 Receptor Pathway Mediated by Gut Microbiota.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {831881}, pmid = {35273587}, issn = {1664-302X}, abstract = {Growing body of research indicates that Traditional Chinese Medicine (TCM) interact with gut microbiota (GM) after oral administration. Radix Rehmanniae and Cornus Officinalis (RR-CO), a well-known TCM pair, is often used to treat diabetes mellitus (DM) and its complications. The current study aimed to explore the protective effects of RR-CO on DM induced testicular damage by modulating GM. The RR-CO treatments significantly reduced hyperglycemia, ameliorated testicular ultrastructural damage and inflammation in DM model to varying degrees. Additionally, 16S-ribosomal DNA (rDNA) sequencing results showed that RR-CO treatment increased the amount of butyric acid-producing GM, such as Clostridiaceae_1 family, and decreased the abundance of Catabacter, Marvinbryantia, and Helicobacter genera. RR-CO fecal bacteria transplantation (RC-FMT) increased the abundance of Clostridiaceae_1 in the Model FMT (M-FMT) group and ameliorated testicular damage. Furthermore, treatment with RR-CO increased the fecal butyric acid level, serum Glucagon-like peptide-1 (GLP-1) level, and testicular GLP-1 receptor (GLP-1R) expression compared to those in DM mice. Finally, intraperitoneal administration of sodium butyrate (SB) significantly improved the pathological damage to the testis and reduced inflammation in the DM group. These data demonstrated a protective effect of RR-CO on DM-induced testicular damage by modulation of GM, which may be mediated by the butyric acid/GLP/GLP-1R pathway.}, }
@article {pmid35271563, year = {2022}, author = {Abbott, A and Montgomery, SP and Chancey, RJ}, title = {Characteristics and Adverse Events of Patients for Whom Nifurtimox Was Released Through CDC-Sponsored Investigational New Drug Program for Treatment of Chagas Disease - United States, 2001-2021.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {71}, number = {10}, pages = {371-374}, pmid = {35271563}, issn = {1545-861X}, mesh = {Adolescent ; Adult ; Aged ; Centers for Disease Control and Prevention, U.S. ; Chagas Disease/*drug therapy ; Child ; Child, Preschool ; *Drug-Related Side Effects and Adverse Reactions ; Drugs, Investigational/adverse effects/*therapeutic use ; Female ; Humans ; Infant ; Male ; Middle Aged ; Nifurtimox/adverse effects/*therapeutic use ; Patients/*statistics &amp; numerical data ; Trypanocidal Agents/adverse effects/*therapeutic use ; United States/epidemiology ; }, abstract = {Chagas disease, or American trypanosomiasis, is caused by the parasite Trypanosoma cruzi. Chagas disease is endemic in rural areas of Latin America, but T. cruzi, triatomine vectors, infected mammalian reservoir hosts, and rare cases of autochthonous vector borne transmission have been reported in the United States (1). Possible modes of transmission include the following: vector borne via skin or mucosal contact with feces of infected triatomine bugs, congenital, blood transfusion, organ transplantation, or laboratory accident. Chagas disease can be treated with benznidazole (commercially available since May 14, 2018) or nifurtimox (2). Before January 25, 2021, nifurtimox (Lampit) had been exclusively available through CDC under an Institutional Review Board-approved Investigational New Drug (IND) treatment protocol, at which time it became reasonably accessible to health care providers outside of the program. This report summarizes CDC Drug Service reports for selected characteristics of and adverse events reported by 336 patients for whom nifurtimox was requested under the CDC IND program during January 1, 2001-January 25, 2021. Of the 336 patients, 34.2% resided in California. Median age of patients was 37 years (range = 1-78 years). Most patients were aged ≥18 (91.8%; 305 of 332) and Hispanic (93.2%; 290 of 311). Among the patients with available information, 91.4% (222 of 243) reported an adverse event. Among those with information about the severity of their adverse events, 20.5% reported a severe event. On August 7, 2020, the Food and Drug Administration (FDA) announced approval of a nifurtimox product, Lampit (Bayer), for treatment of Chagas disease in patients aged <18 years weighing ≥5.5 lbs (≥2.5 kg). Lampit became commercially available during October 2020. Physicians should take frequency of adverse events into consideration when prescribing nifurtimox and counseling patients.}, }
@article {pmid35271405, year = {2022}, author = {Rotz, SJ and Sangwan, N and Nagy, M and Tzeng, A and Jia, M and Moncaliano, M and Majhail, NS and Eng, C}, title = {Fecal microbiota of adolescent and young adult cancer survivors and metabolic syndrome: an exploratory study.}, journal = {Pediatric hematology and oncology}, volume = {39}, number = {7}, pages = {629-643}, pmid = {35271405}, issn = {1521-0669}, support = {KL2 TR002547/TR/NCATS NIH HHS/United States ; R01 CA215134/CA/NCI NIH HHS/United States ; }, mesh = {Adiponectin ; Adolescent ; Biomarkers ; C-Reactive Protein ; *Cancer Survivors ; Child ; Cross-Sectional Studies ; Cytokines ; Glycated Hemoglobin ; Humans ; Interleukin-10 ; Interleukin-6 ; Lectins ; Leptin ; *Metabolic Syndrome ; *Microbiota ; Obesity ; Tumor Necrosis Factor-alpha ; Young Adult ; }, abstract = {Metabolic syndrome and obesity occur commonly in long-term pediatric cancer survivors. The intestinal microbiome is associated with metabolic syndrome and obesity in the general population, and is perturbed during cancer therapy. We aimed to determine if long-term survivors of pediatric cancer would have reduced bacterial microbiome diversity, and if these findings would be associated with components of the metabolic syndrome, obesity, and chronic inflammation. We performed a cross-sectional exploratory study examining the intestinal microbiome via 16S amplicon sequencing, treatment history, clinical measurements (blood pressure, body mass index) and biomarkers (hemoglobin A1c, lipoproteins, adiponectin: leptin ratio, C-reactive protein, TNFα, Interleukin-6, and Interleukin-10) between 35 long-term survivors and 32 age, sex, and race matched controls. All subjects were aged 10-40 years, and survivors were at least five years from therapy completion. Survivors had lower alpha diversity compared to controls (Shannon index p = .001, Simpson index p = .032) and differently abundant bacterial taxa. Further, among survivors, those who received radiation (18/35) to the central nervous system or abdomen/pelvis had decreased alpha diversity compared to those who did not receive radiation (Shannon and Simpson p < .05 for both). Although, no specific component of metabolic syndrome or cytokine was associated with measures of alpha diversity, survivors with low adiponectin-lectin ratio, elevated body mass index, and elevated C-reactive protein had differently abundant taxa compared to those with normal measures. The microbiome of cancer survivors remains less diverse than controls even many years after diagnosis, and exposure to radiation may lead to further loss of diversity in survivors.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2049937.}, }
@article {pmid35271353, year = {2022}, author = {Fobofou, SA and Savidge, T}, title = {Microbial metabolites: cause or consequence in gastrointestinal disease?.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {322}, number = {6}, pages = {G535-G552}, pmid = {35271353}, issn = {1522-1547}, support = {R01 NR013497/NR/NINR NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 DK130517/DK/NIDDK NIH HHS/United States ; P01 AI152999/AI/NIAID NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; }, mesh = {*COVID-19 ; Dysbiosis/microbiology ; *Gastrointestinal Diseases ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Systems biology studies have established that changes in gastrointestinal microbiome composition and function can adversely impact host physiology. Notable diseases synonymously associated with dysbiosis include inflammatory bowel diseases, cancer, metabolic disorders, and opportunistic and recurrent pathogen infections. However, there is a scarcity of mechanistic data that advances our understanding of taxonomic correlations with pathophysiological host-microbiome interactions. Generally, to survive a hostile gut environment, microbes are highly metabolically active and produce trans-kingdom signaling molecules to interact with competing microorganisms and the host. These specialized metabolites likely play important homeostatic roles, and identifying disease-specific taxa and their effector pathways can provide better strategies for diagnosis, treatment, and prevention, as well as the discovery of innovative therapeutics. The signaling role of microbial biotransformation products such as bile acids, short-chain fatty acids, polysaccharides, and dietary tryptophan is increasingly recognized, but little is known about the identity and function of metabolites that are synthesized by microbial biosynthetic gene clusters, including ribosomally synthesized and posttranslationally modified peptides (RiPPs), nonribosomal peptides (NRPs), polyketides (PKs), PK-NRP hybrids, and terpenes. Here we consider how bioactive natural products directly encoded by the human microbiome can contribute to the pathophysiology of gastrointestinal disease, cancer, autoimmune, antimicrobial-resistant bacterial and viral infections (including COVID-19). We also present strategies used to discover these compounds and the biological activities they exhibit, with consideration of therapeutic interventions that could emerge from understanding molecular causation in gut microbiome research.}, }
@article {pmid35269538, year = {2022}, author = {Li, Z and Li, Y and Sun, Q and Wei, J and Li, B and Qiu, Y and Liu, K and Shao, D and Ma, Z}, title = {Targeting the Pulmonary Microbiota to Fight against Respiratory Diseases.}, journal = {Cells}, volume = {11}, number = {5}, pages = {}, pmid = {35269538}, issn = {2073-4409}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Lung ; *Microbiota/physiology ; *Probiotics/therapeutic use ; }, abstract = {The mucosal immune system of the respiratory tract possesses an effective "defense barrier" against the invading pathogenic microorganisms; therefore, the lungs of healthy organisms are considered to be sterile for a long time according to the strong pathogens-eliminating ability. The emergence of next-generation sequencing technology has accelerated the studies about the microbial communities and immune regulating functions of lung microbiota during the past two decades. The acquisition and maturation of respiratory microbiota during childhood are mainly determined by the birth mode, diet structure, environmental exposure and antibiotic usage. However, the formation and development of lung microbiota in early life might affect the occurrence of respiratory diseases throughout the whole life cycle. The interplay and crosstalk between the gut and lung can be realized by the direct exchange of microbial species through the lymph circulation, moreover, the bioactive metabolites produced by the gut microbiota and lung microbiota can be changed via blood circulation. Complicated interactions among the lung microbiota, the respiratory viruses, and the host immune system can regulate the immune homeostasis and affect the inflammatory response in the lung. Probiotics, prebiotics, functional foods and fecal microbiota transplantation can all be used to maintain the microbial homeostasis of intestinal microbiota and lung microbiota. Therefore, various kinds of interventions on manipulating the symbiotic microbiota might be explored as novel effective strategies to prevent and control respiratory diseases.}, }
@article {pmid35268045, year = {2022}, author = {Li, W and Zhang, L and Xu, Q and Yang, W and Zhao, J and Ren, Y and Yu, Z and Ma, L}, title = {Taxifolin Alleviates DSS-Induced Ulcerative Colitis by Acting on Gut Microbiome to Produce Butyric Acid.}, journal = {Nutrients}, volume = {14}, number = {5}, pages = {}, pmid = {35268045}, issn = {2072-6643}, mesh = {Animals ; Butyric Acid/pharmacology ; *Colitis, Ulcerative/chemically induced/drug therapy/metabolism ; Dextran Sulfate/pharmacology ; *Gastrointestinal Microbiome ; Mice ; Quercetin/analogs &amp; derivatives ; RNA, Ribosomal, 16S ; }, abstract = {Taxifolin is a bioflavonoid which has been used to treat Inflammatory Bowel Disease. However, taxifolin on DSS-induced colitis and gut health is still unclear. Here, we studied the effect of taxifolin on DSS-induced intestinal mucositis in mice. We measured the degree of intestinal mucosal injury and inflammatory response in DSS treated mice with or without taxifolin administration and studied the changes of fecal metabolites and intestinal microflora using 16S rRNA. The mechanism was further explored by fecal microbiota transplantation. The results showed that the weight loss and diarrhea score of the mice treated with taxifolin decreased in DSS-induced mice and longer colon length was displayed after taxifolin supplementation. Meanwhile, the expression of GPR41 and GPR43 in the colon was significantly increased by taxifolin treatment. Moreover, the expression of TNF-α, IL-1β, and IL-6 in colon tissue was inhibited by taxifolin treatment. The fecal metabolism pattern changed significantly after DSS treatment, which was reversed by taxifolin treatment. Importantly, taxifolin significantly increased the levels of butyric acid and isobutyric acid in the feces of DSS-treated mice. In terms of gut flora, taxifolin reversed the changes of Akkermansia, and further decreased uncultured_bacterium_f_Muribaculaceae. Fecal transplantation from taxifolin-treated mice showed a lower diarrhea score, reduced inflammatory response in the colon, and reduced intestinal mucosal damage, which may be related to the increased level of butyric acid in fecal metabolites. In conclusion, this study provides evidence that taxifolin can ameliorate DSS-induced colitis by altering gut microbiota to increase the production of SCFAs.}, }
@article {pmid35266816, year = {2022}, author = {He, S and Cui, S and Song, W and Jiang, Y and Chen, H and Liao, D and Lu, X and Li, J and Chen, X and Peng, L}, title = {Interleukin-17 Weakens the NAFLD/NASH Process by Facilitating Intestinal Barrier Restoration Depending on the Gut Microbiota.}, journal = {mBio}, volume = {13}, number = {2}, pages = {e0368821}, pmid = {35266816}, issn = {2150-7511}, support = {2018A030313970//National Science Fundation of Guangdong/ ; 34001004//Fundamental Research Funds for Initial Funding/ ; 2019M662871//China Postdoctoral Science Foundation/ ; 2020T130133//China Postdoctoral Science Foundation/ ; 81900506//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Diet, High-Fat ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; Interleukin-17/*metabolism ; Methionine/pharmacology ; Mice ; *Non-alcoholic Fatty Liver Disease/microbiology ; }, abstract = {Interleukin-17 (IL-17) is associated with nonalcoholic fatty liver disease (NAFLD) and gut microbiota, and how IL-17 mediates the NAFLD/nonalcoholic steatohepatitis (NASH) process depending on the gut microbiota is unclear. We found that T helper 17 (TH17) cells were decreased in the small intestine in a methionine choline-deficient (MCD) diet-induced NASH model. IL-17-deficient (Il17[-/-]) mice showed alterations in intestinal microbiota, including the inhibition of probiotic growth and the overgrowth of certain pathogenic bacteria, and were prone to higher endotoxemia levels and more severe gastrointestinal barrier defects than wild-type (WT) mice. Furthermore, TH17 cells were responsible for restoring the intestinal barrier after administration of recombinant IL-17 to Il17[-/-] mice or injection of CD4[+] T cells into a Rag1[-/-] mouse model. Additionally, transplantation of the microbiota from WT mice to Il17[-/-] mice restored the intestinal barrier. Notably, microbiota-depleted Il17[-/-] mice were resistant to MCD diet-induced intestinal barrier impairment. Fecal microbiota transplantation from Il17[-/-] mice to microbiota-depleted mice aggravated intestinal barrier impairment and then promoted the development of NASH. Collectively, this study showed that host IL-17 could strengthen intestinal mucosal barrier integrity and reduce dysbiosis-induced intestinal injury and secondary extraintestinal organ injury induced by a special diet. IMPORTANCE The morbidity of NASH has increased, with limited effective treatment options. IL-17 plays a protective role in the gut mucosa in high-fat-diet (HFD)-related metabolic disorders, and HFD-related microbiota dysbiosis is responsible for a decreased number of T helper 17 (TH17) cells in the lamina propria. The mechanism by which IL-17 mediates the NAFLD/NASH process depending on the gut microbiota is unclear. In our study, IL-17 originating from TH17 cells maintained intestinal barrier integrity and determined the outcomes of diet-related disease, which may be a target strategy for NAFLD/NASH.}, }
@article {pmid35262957, year = {2023}, author = {Hu, C and Xu, B and Wang, X and Wan, WH and Lu, J and Kong, D and Jin, Y and You, W and Sun, H and Mu, X and Feng, D and Chen, Y}, title = {Gut microbiota-derived short-chain fatty acids regulate group 3 innate lymphoid cells in HCC.}, journal = {Hepatology (Baltimore, Md.)}, volume = {77}, number = {1}, pages = {48-64}, pmid = {35262957}, issn = {1527-3350}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Interleukin-17 ; Immunity, Innate ; *Carcinoma, Hepatocellular/metabolism ; Lymphocytes ; *Liver Neoplasms/metabolism ; Fatty Acids, Volatile/metabolism ; Acetates ; }, abstract = {BACKGROUND AND AIMS: Type 3 innate lymphoid cells (ILC3s) are essential for host defense against infection and tissue homeostasis. However, their role in the development of HCC has not been adequately confirmed. In this study, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) derived from intestinal microbiota in ILC3 regulation.<br><br>APPROACH AND RESULTS: We report that Lactobacillus reuteri was markedly reduced in the gut microbiota of mice with HCC, accompanied by decreased SCFA levels, especially acetate. Additionally, transplantation of fecal bacteria from wild-type mice or L. reuteri could promote an anticancer effect, elevate acetate levels, and reduce IL-17A secretion in mice with HCC. Mechanistically, acetate reduced the production of IL-17A in hepatic ILC3s by inhibiting histone deacetylase activity, increasing the acetylation of SRY (sex-determining region Y)-box transcription factor 13 (Sox13) at site K30, and decreasing expression of Sox13. Moreover, the combination of acetate with programmed death 1/programmed death ligand 1 blockade significantly enhanced antitumor immunity. Consistently, tumor-infiltrating ILC3s correlated with negative prognosis in patients with HCC, which could be functionally mediated by acetate.<br><br>CONCLUSIONS: These findings suggested that modifying bacteria, changing SCFAs, reducing IL-17A-producing ILC3 infiltration, and combining with immune checkpoint inhibitors will contribute to the clinical treatment of HCC.}, }
@article {pmid35259427, year = {2022}, author = {Vicentini, FA and Szamosi, JC and Rossi, L and Griffin, L and Nieves, K and Bihan, D and Lewis, IA and Pittman, QJ and Swain, MG and Surette, MG and Hirota, SA and Sharkey, KA}, title = {Colitis-associated microbiota drives changes in behaviour in male mice in the absence of inflammation.}, journal = {Brain, behavior, and immunity}, volume = {102}, number = {}, pages = {266-278}, doi = {10.1016/j.bbi.2022.03.001}, pmid = {35259427}, issn = {1090-2139}, mesh = {Animals ; *Colitis/chemically induced ; Dextran Sulfate/pharmacology ; Disease Models, Animal ; Inflammation ; *Inflammatory Bowel Diseases ; Male ; Mice ; Mice, Inbred C57BL ; *Microbiota ; }, abstract = {Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. IBD are associated with a high prevalence of cognitive, behavioural and emotional comorbidities, including anxiety and depression. The link between IBD and the development of behavioural comorbidities is poorly understood. As the intestinal microbiota profoundly influences host behaviour, we sought to determine whether the altered gut microbiota associated with intestinal inflammation contributes to the development of behavioural abnormalities. Using the dextran sulphate sodium (DSS) model of colitis, we characterized intestinal inflammation, behaviour (elevated plus maze and tail suspension test) and the composition of the microbiota in male mice. Cecal contents from colitic mice were transferred into germ-free (GF) or antibiotic (Abx)-treated mice, and behaviour was characterized in recipient mice. Gene expression was measured using qPCR. DSS colitis was characterized by a significant reduction in body weight and an increase in colonic inflammatory markers. These changes were accompanied by increased anxiety-like behaviour, an altered gut microbiota composition, and increased central Tnf expression. Transfer of the cecal matter from colitic mice induced similar behavioural changes in both GF and Abx-treated recipient mice, with no signs of colonic or neuroinflammation. Upon characterization of the microbiota in donor and recipient mice, specific taxa were found to be associated with behavioural changes, notably members of the Lachnospiraceae family. Behavioural abnormalities associated with intestinal inflammation are transmissible via transfer of cecal matter, suggesting that alterations in the composition of the gut microbiota play a key role in driving behavioural changes in colitis.}, }
@article {pmid35258452, year = {2022}, author = {Zhang, X and Zhang, X and Tong, F and Cai, Y and Zhang, Y and Song, H and Tian, X and Yan, C and Han, Y}, title = {Gut microbiota induces high platelet response in patients with ST segment elevation myocardial infarction after ticagrelor treatment.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35258452}, issn = {2050-084X}, mesh = {Animals ; Dysbiosis/drug therapy ; *Gastrointestinal Microbiome ; Humans ; Mice ; *Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/pharmacokinetics/therapeutic use ; *ST Elevation Myocardial Infarction/drug therapy ; Ticagrelor/therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Ticagrelor is a first-line drug for the treatment of acute ST elevation myocardial infarction (STEMI). However, approximately 20% STEMI patients taking ticagrelor exhibited a delayed response and the mechanism was still unclear.<br><br>METHODS: To explore the mechanism of the poor response of ticagrelor in post-percutaneous coronary intervention (PCI) patients, we enrolled 65 high platelet reactivity (HPR) patients and 90 controls (normal platelet reactivity [NPR]). Pharmacokinetic assessment result showed that the plasma concentrations of ticagrelor and its metabolism production, AR-C124910XX, were lower in HPR patients than controls. Further single nucloetide polymorphism (SNP) analysis identified that there is no difference in ATP binding cassette subfamily B member 1 (ABCB1) gene expression between the NPR group and the HPR group. Metagenomic and metabolomic analyses of fecal samples showed that HPR patients had higher microbial richness and diversity. Transplantation of the gut microbiota from HPR donors to microbiota-depleted mice obviously decreased plasma concentration of ticagrelor.<br><br>RESULTS: Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with STEMI and support that modify gut microbiota is a potential therapeutic option for STEMI.<br><br>CONCLUSIONS: Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with ST elevation myocardial infarction (STEMI) and support that modify gut microbiota is a potential therapeutic option for STEMI.<br><br>FUNDING: NSFC 82170297 and 82070300 from the National Natural Science Foundation of China.}, }
@article {pmid35255932, year = {2022}, author = {Gebrayel, P and Nicco, C and Al Khodor, S and Bilinski, J and Caselli, E and Comelli, EM and Egert, M and Giaroni, C and Karpinski, TM and Loniewski, I and Mulak, A and Reygner, J and Samczuk, P and Serino, M and Sikora, M and Terranegra, A and Ufnal, M and Villeger, R and Pichon, C and Konturek, P and Edeas, M}, title = {Microbiota medicine: towards clinical revolution.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {111}, pmid = {35255932}, issn = {1479-5876}, mesh = {Dysbiosis/therapy ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Humans ; *Microbiota ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrated, more than a decade ago, that the gut microbial alteration is a key factor in the pathogenesis of many local and systemic disorders. In this regard, a deep understanding of the mechanisms involved in the gut microbial symbiosis/dysbiosis is crucial for the clinical and health field. We review the most recent studies on the involvement of gut microbiota in the pathogenesis of many diseases. We also elaborate the different strategies used to manipulate the gut microbiota in the prevention and treatment of disorders. The future of medicine is strongly related to the quality of our microbiota. Targeting microbiota dysbiosis will be a huge challenge.}, }
@article {pmid35252301, year = {2022}, author = {Yao, Q and Fan, L and Zheng, N and Blecker, C and Delcenserie, V and Li, H and Wang, J}, title = {2'-Fucosyllactose Ameliorates Inflammatory Bowel Disease by Modulating Gut Microbiota and Promoting MUC2 Expression.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {822020}, pmid = {35252301}, issn = {2296-861X}, abstract = {Gut microbiota dysbiosis, together with goblet cells dysfunction has been observed in ulcerative colitis cases. This study aims to evaluate the potential of 2'-fucosyllactose (2'-FL) supplementation in inhibiting intestinal inflammation through regulating gut microbiota, protecting goblet cells, and stimulating mucin secretion. 2'-FL was orally administered to C57BL/6J mice daily (400 mg/kg bw) for 21 days and 5% dextran sulfate sodium (DSS) was used to induce the colitis in the last 7 days. Meanwhile, fecal microbiota transplantation (FMT) was conducted to test the roles of gut microbiota in the remission of colitis by 2'-FL. Gut microbiota alteration was analyzed through 16S ribosomal RNA (16S rRNA) sequencing. Periodic acid-Schiff (PAS), immunofluorescence staining, as well as mucin 2 (MUC2) and NOD-like receptor family pyrin domain containing 6 (NLRP6) messenger RNA (mRNA) expression in colon fragments was performed and detected. The results showed that the DSS + 2'-FL mice were found to have a slower rate of weight loss, lower disease activity index (DAI) scores, and longer colon lengths than the DSS group (p < 0.05), so in the FMT recipient mice which received fecal microbiota from the DSS + 2'-FL group. In addition, the data revealed that 2'-FL relieved the disorder of DSS-induced gut microbiota, including decreasing the high abundance of mucin-utilizing bacteria in the DSS group, such as Bacteroides, Lachnospiraceae NK4A136, Lachnospiraceae, and Bacteroides vulgatus. PAS and immunofluorescence staining showed that 2'-FL treatment promoted the recovery of goblet cells and enhanced MUC2 and NLRP6 expression, which was also observed in the FM (DSS + 2'-FL) group. Moreover, NLRP6, which has been proved to be a negative regulator for Toll-like receptor 4/myeloid differential protein-8/nuclear factor-kappa B (TLR4/MyD88/NF-κB) pathway, was upregulated by 2'-FL in colon tissue. In conclusion, this study suggests that 2'-FL ameliorates colitis in a gut microbiota-dependent manner. The underlying protective mechanism associates with the recovery of goblet cells number and improves MUC2 secretion through TLR4-related pathway.}, }
@article {pmid35250668, year = {2022}, author = {Doll, JPK and Vázquez-Castellanos, JF and Schaub, AC and Schweinfurth, N and Kettelhack, C and Schneider, E and Yamanbaeva, G and Mählmann, L and Brand, S and Beglinger, C and Borgwardt, S and Raes, J and Schmidt, A and Lang, UE}, title = {Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression-Case Report.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {815422}, pmid = {35250668}, issn = {1664-0640}, abstract = {Depression is a debilitating disorder, and at least one third of patients do not respond to therapy. Associations between gut microbiota and depression have been observed in recent years, opening novel treatment avenues. Here, we present the first two patients with major depressive disorder ever treated with fecal microbiota transplantation as add-on therapy. Both improved their depressive symptoms 4 weeks after the transplantation. Effects lasted up to 8 weeks in one patient. Gastrointestinal symptoms, constipation in particular, were reflected in microbiome changes and improved in one patient. This report suggests further FMT studies in depression could be worth pursuing and adds to awareness as well as safety assurance, both crucial in determining the potential of FMT in depression treatment.}, }
@article {pmid35247461, year = {2022}, author = {Benech, N and Rolhion, N and Sokol, H}, title = {Gut Microbiota Reprogramming of Tryptophan Metabolism During Pregnancy Shapes Host Insulin Resistance.}, journal = {Gastroenterology}, volume = {162}, number = {6}, pages = {1587-1589}, doi = {10.1053/j.gastro.2022.01.059}, pmid = {35247461}, issn = {1528-0012}, mesh = {Female ; *Gastrointestinal Microbiome ; Humans ; *Insulin Resistance ; *Microbiota ; Pregnancy ; Tryptophan ; }, }
@article {pmid35245613, year = {2022}, author = {Dong, S and Sun, M and He, C and Cheng, H}, title = {Brain-gut-microbiota axis in Parkinson's disease: A historical review and future perspective.}, journal = {Brain research bulletin}, volume = {183}, number = {}, pages = {84-93}, doi = {10.1016/j.brainresbull.2022.02.015}, pmid = {35245613}, issn = {1873-2747}, mesh = {Animals ; Brain/metabolism ; Brain-Gut Axis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; *Parkinson Disease/metabolism ; }, abstract = {Parkinson's disease (PD) is the second most common degenerative disease of the central nervous system (CNS) after Alzheimer's disease. In addition to the typical motor symptoms, the clinical manifestations of patients with PD include gastrointestinal symptoms, which even precede the motor symptoms. Recent research has found that the gut microbiota regulates the brain-gut axial interaction through immune, endocrine, and direct neural mechanisms, supporting the hypothesis that the pathological process of PD spreads from the gut to the brain. In this review article, we highlight the landmark findings in the field of PD, with particular attention to the brain-gut-microbiota axis. We summarize the changes and their clinical effects on the gut microbiota and metabolites observed in PD. The intestinal microbiota may contain appropriate targets for the prevention and treatment of PD. Clinical cohort studies suggest that certain intestinal microbes have protective or pathogenic effects on the progression of PD. A better understanding of the interaction between the gut-brain axis, the gut microbiota, and PD has the potential to lead to new diagnostic and therapeutic approaches. Animal experiments suggest that fecal microbiota transplantation (FMT) is helpful for treating PD, and FMT is expected to be an effective treatment for PD in the future.}, }
@article {pmid35243943, year = {2023}, author = {Zhao, Y and Li, M and Wang, Y and Geng, R and Fang, J and Liu, Q and Kang, SG and Zeng, WC and Huang, K and Tong, T}, title = {Understanding the mechanism underlying the anti-diabetic effect of dietary component: a focus on gut microbiota.}, journal = {Critical reviews in food science and nutrition}, volume = {63}, number = {25}, pages = {7378-7398}, doi = {10.1080/10408398.2022.2045895}, pmid = {35243943}, issn = {1549-7852}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *COVID-19 ; *Diabetes Mellitus ; Diet ; *Probiotics/therapeutic use ; Dysbiosis ; }, abstract = {Diabetes has become one of the biggest non-communicable diseases and threatens human health worldwide. The management of diabetes is a complex and multifaceted process including drug therapy and lifestyle interventions. Dietary components are essential for both diabetes management and health and survival of trillions of the gut microbiota (GM). Herein, we will discuss the relationship between diets and GM, the mechanism linking diabetes and gut dysbiosis, and the effects of dietary components (nutrients, phytochemicals, probiotics, food additives, etc.) on diabetes from the perspective of modulating GM. The GM of diabetic patients differs from that of health individuals and GM disorder contributes to the onset and maintenance of diabetes. Studies in humans and animal models consolidate that dietary component is a key regulator of diabetes and increasing evidence suggests that the alteration of GM plays a salient role in dietary interventions for diabetes. Given that diabetes is a major public health issue, especially that diabetes is linked with a high risk of mortality from COVID-19, this review provides compelling evidence for that targeting GM by dietary components is a promising strategy, and offers new insights into potential preventive or therapeutic approaches (dietary and pharmacological intervention) for the clinical management of diabetes.}, }
@article {pmid35242797, year = {2022}, author = {Zhang, T and Gao, G and Sakandar, HA and Kwok, LY and Sun, Z}, title = {Gut Dysbiosis in Pancreatic Diseases: A Causative Factor and a Novel Therapeutic Target.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {814269}, pmid = {35242797}, issn = {2296-861X}, abstract = {Pancreatic-related disorders such as pancreatitis, pancreatic cancer, and type 1 diabetes mellitus (T1DM) impose a substantial challenge to human health and wellbeing. Even though our understanding of the initiation and progression of pancreatic diseases has broadened over time, no effective therapeutics is yet available for these disorders. Mounting evidence suggests that gut dysbiosis is closely related to human health and disease, and pancreatic diseases are no exception. Now much effort is under way to explore the correlation and eventually potential causation between the gut microbiome and the course of pancreatic diseases, as well as to develop novel preventive and/or therapeutic strategies of targeted microbiome modulation by probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT) for these multifactorial disorders. Attempts to dissect the intestinal microbial landscape and its metabolic profile might enable deep insight into a holistic picture of these complex conditions. This article aims to review the subtle yet intimate nexus loop between the gut microbiome and pancreatic diseases, with a particular focus on current evidence supporting the feasibility of preventing and controlling pancreatic diseases via microbiome-based therapeutics and therapies.}, }
@article {pmid35242721, year = {2022}, author = {Zhou, Z and Sun, B and Yu, D and Zhu, C}, title = {Gut Microbiota: An Important Player in Type 2 Diabetes Mellitus.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {834485}, pmid = {35242721}, issn = {2235-2988}, mesh = {Animals ; *Diabetes Mellitus, Type 2/metabolism/therapy ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {Type 2 diabetes mellitus (T2DM) is one of the common metabolic diseases in the world. Due to the rise in morbidity and mortality, it has become a global health problem. To date, T2DM still cannot be cured, and its intervention measures mainly focus on glucose control as well as the prevention and treatment of related complications. Interestingly, the gut microbiota plays an important role in the development of metabolic diseases, especially T2DM. In this review, we introduce the characteristics of the gut microbiota in T2DM population, T2DM animal models, and diabetic complications. In addition, we describe the molecular mechanisms linking host and the gut microbiota in T2DM, including the host molecules that induce gut microbiota dysbiosis, immune and inflammatory responses, and gut microbial metabolites involved in pathogenesis. These findings suggest that we can treat T2DM and its complications by remodeling the gut microbiota through interventions such as drugs, probiotics, prebiotics, fecal microbiota transplantation (FMT) and diets.}, }
@article {pmid35241180, year = {2022}, author = {Hu, J and Deng, F and Zhao, B and Lin, Z and Sun, Q and Yang, X and Wu, M and Qiu, S and Chen, Y and Yan, Z and Luo, S and Zhao, J and Liu, W and Li, C and Liu, KX}, title = {Lactobacillus murinus alleviate intestinal ischemia/reperfusion injury through promoting the release of interleukin-10 from M2 macrophages via Toll-like receptor 2 signaling.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {38}, pmid = {35241180}, issn = {2049-2618}, mesh = {Animals ; Humans ; Interleukin-10 ; Ischemia ; Lactobacillus ; Macrophages ; Mice ; Mice, Inbred C57BL ; *Reperfusion Injury/drug therapy ; *Toll-Like Receptor 2 ; }, abstract = {BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury has high morbidity and mortality rates. Gut microbiota is a potential key factor affecting intestinal I/R injury. Populations exhibit different sensitivities to intestinal I/R injury; however, whether this interpopulation difference is related to variation in gut microbiota is unclear. Here, to elucidate the interaction between the gut microbiome and intestinal I/R injury, we performed 16S DNA sequencing on the preoperative feces of C57BL/6 mice and fecal microbiota transplantation (FMT) experiments in germ-free mice. The transwell co-culture system of small intestinal organoids extracted from control mice and macrophages extracted from control mice or Toll-like receptor 2 (TLR2)-deficient mice or interleukin-10 (IL-10)-deficient mice were established separately to explore the potential mechanism of reducing intestinal I/R injury.<br><br>RESULTS: Intestinal I/R-sensitive (Sen) and intestinal I/R-resistant (Res) mice were first defined according to different survival outcomes of mice suffering from intestinal I/R. Fecal microbiota composition and diversity prior to intestinal ischemia differed between Sen and Res mice. The relative abundance of Lactobacillus murinus (L. murinus) at the species level was drastically higher in Res than that in Sen mice. Clinically, the abundance of L. murinus in preoperative feces of patients undergoing cardiopulmonary bypass surgery was closely related to the degree of intestinal I/R injury after surgery. Treatment with L. murinus significantly prevented intestinal I/R-induced intestinal injury and improved mouse survival, which depended on macrophages involvement. Further, in vitro experiments indicated that promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury.<br><br>CONCLUSION: The gut microbiome is involved in the postoperative outcome of intestinal I/R. Lactobacillus murinus alleviates mice intestinal I/R injury through macrophages, and promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury. This study revealed a novel mechanism of intestinal I/R injury and a new therapeutic strategy for clinical practice. Video Abstract.}, }
@article {pmid35237276, year = {2022}, author = {Yang, Y and Zheng, X and Wang, Y and Tan, X and Zou, H and Feng, S and Zhang, H and Zhang, Z and He, J and Cui, B and Zhang, X and Wu, Z and Dong, M and Cheng, W and Tao, S and Wei, H}, title = {Human Fecal Microbiota Transplantation Reduces the Susceptibility to Dextran Sulfate Sodium-Induced Germ-Free Mouse Colitis.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {836542}, pmid = {35237276}, issn = {1664-3224}, mesh = {Animals ; Anti-Inflammatory Agents/pharmacology ; Bacteria/metabolism ; *Colitis/drug therapy/therapy ; *Colitis, Ulcerative/drug therapy/therapy ; Dextran Sulfate/toxicity ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including Alistipes putredinis, Akkermansia muciniphila, Bifidobacterium adolescentis, short-chain fatty acids (SCFAs)-producing bacterium Christensenella minuta, and secondary bile acids (SBAs)-producing bacterium Clostridium leptum. In the UC intervention group, the SCFA-producing bacterium Bacteroides stercoris, IBD-related bacterium Ruminococcus gnavus, Enterococcus faecalis, and the conditional pathogen Bacteroides caccae, were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.}, }
@article {pmid35236743, year = {2022}, author = {Renga, G and Nunzi, E and Pariano, M and Puccetti, M and Bellet, MM and Pieraccini, G and D'Onofrio, F and Santarelli, I and Stincardini, C and Aversa, F and Riuzzi, F and Antognelli, C and Gargaro, M and Bereshchenko, O and Ricci, M and Giovagnoli, S and Romani, L and Costantini, C}, title = {Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite.}, journal = {Journal for immunotherapy of cancer}, volume = {10}, number = {3}, pages = {}, pmid = {35236743}, issn = {2051-1426}, mesh = {Animals ; *Colitis/chemically induced/drug therapy ; Humans ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Mice ; *Neoplasms/drug therapy ; Treatment Outcome ; Tryptophan/pharmacology ; }, abstract = {BACKGROUND: Despite the great success, the therapeutic benefits of immune checkpoint inhibitors (ICIs) in cancer immunotherapy are limited by either various resistance mechanisms or ICI-associated toxic effects including gastrointestinal toxicity. Thus, novel therapeutic strategies that provide manageable side effects to existing ICIs would enhance and expand their therapeutic efficacy and application. Due to its proven role in cancer development and immune regulation, gut microbiome has gained increasing expectation as a potential armamentarium to optimize immunotherapy with ICI. However, much has to be learned to fully harness gut microbiome for clinical applicability. Here we have assessed whether microbial metabolites working at the interface between microbes and the host immune system may optimize ICI therapy.<br><br>METHODS: To this purpose, we have tested indole-3-carboxaldehyde (3-IAld), a microbial tryptophan catabolite known to contribute to epithelial barrier function and immune homeostasis in the gut via the aryl hydrocarbon receptor (AhR), in different murine models of ICI-induced colitis. Epithelial barrier integrity, inflammation and changes in gut microbiome composition and function were analyzed. AhR, indoleamine 2,3-dioxygenase 1, interleukin (IL)-10 and IL-22 knockout mice were used to investigate the mechanism of 3-IAld activity. The function of the microbiome changes induced by 3-IAld was evaluated on fecal microbiome transplantation (FMT). Finally, murine tumor models were used to assess the effect of 3-IAld treatment on the antitumor activity of ICI.<br><br>RESULTS: On administration to mice with ICI-induced colitis, 3-IAld protected mice from intestinal damage via a dual action on both the host and the microbes. Indeed, paralleling the activation of the host AhR/IL-22-dependent pathway, 3-IAld also affected the composition and function of the microbiota such that FMT from 3-IAld-treated mice protected against ICI-induced colitis with the contribution of butyrate-producing bacteria. Importantly, while preventing intestinal damage, 3-IAld did not impair the antitumor activity of ICI.<br><br>CONCLUSIONS: This study provides a proof-of-concept demonstration that moving past bacterial phylogeny and focusing on bacterial metabolome may lead to a new class of discrete molecules, and that working at the interface between microbes and the host immune system may optimize ICI therapy.}, }
@article {pmid35234303, year = {2022}, author = {Majewska-Szczepanik, M and Kowalczyk, P and Marcińska, K and Strzępa, A and Lis, GJ and Wong, FS and Szczepanik, M and Wen, L}, title = {Obesity aggravates contact hypersensitivity reaction in mice.}, journal = {Contact dermatitis}, volume = {87}, number = {1}, pages = {28-39}, pmid = {35234303}, issn = {1600-0536}, support = {IP2012 0443 72//Ministry of Science and Higher Education/ ; UL1 TR001863/TR/NCATS NIH HHS/United States ; K/ZDS/007123//Ministry of Science and Higher Education/ ; DK045735//Foundation for the National Institutes of Health/ ; R01 DK130318/DK/NIDDK NIH HHS/United States ; R01 DK126809/DK/NIDDK NIH HHS/United States ; P30 DK045735/DK/NIDDK NIH HHS/United States ; R01 DK092882/DK/NIDDK NIH HHS/United States ; R01 HD097808/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes ; *Dermatitis, Allergic Contact ; Humans ; Inflammation ; *Interleukin-17 ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity ; }, abstract = {BACKGROUND: Obesity is associated with chronic, low-grade inflammation in tissues and predisposes to various complications, including inflammatory skin diseases. However, the link between obesity and contact hypersensitivity (CHS) is not fully understood.<br><br>OBJECTIVES: We sought to determine the influence of obesity on T helper 1 (Th1)-mediated CHS.<br><br>METHODS: The activity/phenotype/cytokine profile of the immune cells was tested in vivo and in vitro. Using quantitative polymerase chain reaction (qPCR) and fecal microbiota transplantation (FMT), we tested the role of a high-fat diet (HFD)-induced gut microbiota (GM) dysbiosis in increasing the effects of CHS.<br><br>RESULTS: Exacerbated CHS correlates with an increased inflammation-inducing GM in obese mice. We showed a proinflammatory milieu in the subcutaneous adipose tissue of obese mice, accompanied by proinflammatory CD4+ T cells and dendritic cells in skin draining lymph nodes and spleen. Obese interleukin (IL)-17A-/-B6 mice are protected from CHS aggravation, suggesting the importance of IL-17A in CHS aggravation in obesity.<br><br>CONCLUSIONS: Obesity creates a milieu that induces more potent CHS-effector cells but does not have effects on already activated CHS-effector cells. IL-17A is essential for the pathogenesis of enhanced CHS during obesity. Our study provides novel knowledge about antigen-specific responses in obesity, which may help with the improvement of existing treatment and/or in designing novel treatment for obesity-associated skin disorders.}, }
@article {pmid35230889, year = {2022}, author = {Ghani, R and Mullish, BH and Roberts, LA and Davies, FJ and Marchesi, JR}, title = {The potential utility of fecal (or intestinal) microbiota transplantation in controlling infectious diseases.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2038856}, pmid = {35230889}, issn = {1949-0984}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; MR/T005254/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Clostridioides difficile ; *Clostridium Infections/drug therapy/prevention &amp; control ; *Communicable Diseases ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Treatment Outcome ; }, abstract = {The intestinal microbiota is recognized to play a role in the defense against infection, but conversely also acts as a reservoir for potentially pathogenic organisms. Disruption to the microbiome can increase the risk of invasive infection from these organisms; therefore, strategies to restore the composition of the gut microbiota are a potential strategy of key interest to mitigate this risk. Fecal (or Intestinal) Microbiota Transplantation (FMT/IMT), is the administration of minimally manipulated screened healthy donor stool to an affected recipient, and remains the major 'whole microbiome' therapeutic approach at present. Driven by the marked success of using FMT in the treatment of recurrent Clostridioides difficile infection, the potential use of FMT in treating other infectious diseases is an area of active research. In this review, we discuss key examples of this treatment based on recent findings relating to the interplay between microbiota and infection, and potential further exploitations of FMT/IMT.}, }
@article {pmid35229726, year = {2022}, author = {Underhill, DM and Braun, J}, title = {Fungal microbiome in inflammatory bowel disease: a critical assessment.}, journal = {The Journal of clinical investigation}, volume = {132}, number = {5}, pages = {}, pmid = {35229726}, issn = {1558-8238}, mesh = {Animals ; Bacteria ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/genetics/microbiology ; Metagenomics ; Mice ; *Microbiota ; *Mycobiome/genetics ; }, abstract = {The gut microbiome is at the center of inflammatory bowel disease (IBD) pathogenesis and disease activity. While this has mainly been studied in the context of the bacterial microbiome, recent advances have provided tools for the study of host genetics and metagenomics of host-fungal interaction. Through these tools, strong evidence has emerged linking certain fungal taxa, such as Candida and Malassezia, with cellular and molecular pathways of IBD disease biology. Mouse models and human fecal microbial transplant also suggest that some disease-participatory bacteria and fungi may act not via the host directly, but via their fungal-bacterial ecologic interactions. We hope that these insights, and the study design and multi-omics strategies used to develop them, will facilitate the inclusion of the fungal community in basic and translational IBD research.}, }
@article {pmid35227890, year = {2022}, author = {Luo, H and Cao, G and Luo, C and Tan, D and Vong, CT and Xu, Y and Wang, S and Lu, H and Wang, Y and Jing, W}, title = {Emerging pharmacotherapy for inflammatory bowel diseases.}, journal = {Pharmacological research}, volume = {178}, number = {}, pages = {106146}, doi = {10.1016/j.phrs.2022.106146}, pmid = {35227890}, issn = {1096-1186}, mesh = {*Colitis, Ulcerative/complications ; *Crohn Disease/complications ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; Humans ; Inflammation/complications ; *Inflammatory Bowel Diseases/drug therapy ; }, abstract = {Inflammatory bowel disease (IBD) refers to a gamut of disorders that are characterized by chronic intestinal inflammation, including ulcerative colitis (UC) and Crohn's disease (CD), which often leads to mucosal ulceration and progressive loss of intestinal function. The etiopathogenesis of IBD has not been completely clarified, although multiple factors involving genetic modifications, host immune dysfunction, intestinal dysbiosis and environmental effects have been implicated. Currently, pharmacotherapies including both non-targeted and targeted biological agents are widely used for the clinical treatment of IBD. In addition, novel therapeutic approaches that target the intestinal microorganisms, such as fecal microbiota transplantation, antibiotics, probiotics and microbial metabolite inhibitors, are also under development. However, these treatments are either accompanied by side effects or cannot achieve complete clinical remission when used alone. The efficacy and safety of drugs are currently a clinical challenge. Thus, advanced drug delivery systems are needed for targeted delivery of drugs to the inflammatory sites and avoid absorption by healthy tissues. In this review, we have summarized the latest research on the pathogenesis of IBD and the emerging pharmacotherapies, and discussed potential therapeutic targets for innovative therapies.}, }
@article {pmid35227057, year = {2022}, author = {Surwase, SS and Shahriar, SMS and An, JM and Ha, J and Mirzaaghasi, A and Bagheri, B and Park, JH and Lee, YK and Kim, YC}, title = {Engineered Nanoparticles inside a Microparticle Oral System for Enhanced Mucosal and Systemic Immunity.}, journal = {ACS applied materials &amp; interfaces}, volume = {14}, number = {9}, pages = {11124-11143}, doi = {10.1021/acsami.1c24982}, pmid = {35227057}, issn = {1944-8252}, mesh = {Administration, Oral ; Animals ; Antigens/immunology ; Cell Line ; Cell Survival/drug effects ; Cytokines/metabolism ; Female ; Humans ; Hydrogen-Ion Concentration ; Immunity ; Immunity, Mucosal/*drug effects ; Immunoglobulin A/metabolism ; Immunoglobulin G/metabolism ; Mice, Inbred C57BL ; Nanoparticles/*administration &amp; dosage/*chemistry/toxicity ; Ovalbumin/immunology ; Peyer's Patches/immunology ; Spleen/drug effects ; Th1 Cells/metabolism ; Th2 Cells ; Vaccines/administration &amp; dosage/chemical synthesis/chemistry/pharmacokinetics ; Mice ; }, abstract = {Antigen delivery through an oral route requires overcoming multiple challenges, including gastrointestinal enzymes, mucus, and epithelial tight junctions. Although each barrier has a crucial role in determining the final efficiency of the oral vaccination, transcytosis of antigens through follicle-associated epithelium (FAE) represents a major challenge. Most of the research is focused on delivering an antigen to the M-cell for FAE transcytosis because M-cells can easily transport the antigen from the luminal site. However, the fact is that the M-cell population is less than 1% of the total gastrointestinal cells, and most of the oral vaccines have failed to show any effect in clinical trials. To challenge the current dogma of M-cell targeting, in this study, we designed a novel tandem peptide with a FAE-targeting peptide at the front position and a cell-penetrating peptide at the back position. The tandem peptide was attached to a smart delivery system, which overcomes the enzymatic barrier and the mucosal barrier. The result showed that the engineered system could target the FAE (enterocytes and M-cells) and successfully penetrate the enterocytes to reach the dendritic cells located at the subepithelium dome. There was successful maturation and activation of dendritic cells in vitro confirmed by a significant increase in maturation markers such as CD40, CD86, presentation marker MHC I, and proinflammatory cytokines (TNF-α, IL-6, and IL-10). The in vivo results showed a high production of CD4[+] T-lymphocytes (helper T-cell) and a significantly higher production of CD8[+] T-lymphocytes (killer T-cell). Finally, the production of mucosal immunity (IgA) in the trachea, intestine, and fecal extracts and systemic immunity (IgG, IgG1, and IgG2a) was successfully confirmed. To the best of our knowledge, this is the first study that designed a novel tandem peptide to target the FAE, which includes M-cells and enterocytes rather than M-cell targeting and showed that a significant induction of both the mucosal and systemic immune response was achieved compared to M-cell targeting.}, }
@article {pmid35223890, year = {2022}, author = {Amorim, N and McGovern, E and Raposo, A and Khatiwada, S and Shen, S and Koentgen, S and Hold, G and Behary, J and El-Omar, E and Zekry, A}, title = {Refining a Protocol for Faecal Microbiota Engraftment in Animal Models After Successful Antibiotic-Induced Gut Decontamination.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {770017}, pmid = {35223890}, issn = {2296-858X}, abstract = {BACKGROUND: There is mounting evidence for the therapeutic use of faecal microbiota transplant (FMT) in numerous chronic inflammatory diseases. Germ free mice are not always accessible for FMT research and hence alternative approaches using antibiotic depletion prior to FMT in animal studies are often used. Hence, there is a need for standardising gut microbiota depletion and FMT methodologies in animal studies. The aim of this study was to refine gut decontamination protocols prior to FMT engraftment and determine efficiency and stability of FMT engraftment over time.<br><br>METHODS: Male C57BL/6J mice received an antibiotic cocktail consisting of ampicillin, vancomycin, neomycin, and metronidazole in drinking water for 21 days ad libitum. After antibiotic treatment, animals received either FMT or saline by weekly oral gavage for 3 weeks (FMT group or Sham group, respectively), and followed up for a further 5 weeks. At multiple timepoints throughout the model, stool samples were collected and subjected to bacterial culture, qPCR of bacterial DNA, and fluorescent in-situ hybridisation (FISH) to determine bacterial presence and load. Additionally, 16S rRNA sequencing of stool was used to confirm gut decontamination and subsequent FMT engraftment.<br><br>RESULTS: Antibiotic treatment for 7 days was most effective in gut decontamination, as evidenced by absence of bacteria observed in culture, and reduced bacterial concentration, as determined by FISH as well as qPCR. Continued antibiotic administration had no further efficacy on gut decontamination from days 7 to 21. Following gut decontamination, 3 weekly doses of FMT was sufficient for the successful engraftment of donor microbiota in animals. The recolonised animal gut microbiota was similar in composition to the donor sample, and significantly different from the Sham controls as assessed by 16S rRNA sequencing. Importantly, this similarity in composition to the donor sample persisted for 5 weeks following the final FMT dose.<br><br>CONCLUSIONS: Our results showed that 7 days of broad-spectrum antibiotics in drinking water followed by 3 weekly doses of FMT provides a simple, reliable, and cost-effective methodology for FMT in animal research.}, }
@article {pmid35217892, year = {2022}, author = {Shaikh, FY and Gills, JJ and Mohammad, F and White, JR and Stevens, CM and Ding, H and Fu, J and Tam, A and Blosser, RL and Domingue, JC and Larman, TC and Chaft, JE and Spicer, JD and Reuss, JE and Naidoo, J and Forde, PM and Ganguly, S and Housseau, F and Pardoll, DM and Sears, CL}, title = {Murine fecal microbiota transfer models selectively colonize human microbes and reveal transcriptional programs associated with response to neoadjuvant checkpoint inhibitors.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {71}, number = {10}, pages = {2405-2420}, pmid = {35217892}, issn = {1432-0851}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; T32 CA009071/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; T32CA009071/NH/NIH HHS/United States ; KL2TR001077/TR/NCATS NIH HHS/United States ; KL2 TR001077/TR/NCATS NIH HHS/United States ; P30 CA006973/NH/NIH HHS/United States ; K08 CA263316/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Carcinoma, Non-Small-Cell Lung ; Fecal Microbiota Transplantation ; Humans ; *Lung Neoplasms ; Mice ; Neoadjuvant Therapy ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; }, abstract = {Human gut microbial species found to associate with clinical responses to immune checkpoint inhibitors (ICIs) are often tested in mice using fecal microbiota transfer (FMT), wherein tumor responses in recipient mice may recapitulate human responses to ICI treatment. However, many FMT studies have reported only limited methodological description, details of murine cohorts, and statistical methods. To investigate the reproducibility and robustness of gut microbial species that impact ICI responses, we performed human to germ-free mouse FMT using fecal samples from patients with non-small cell lung cancer who had a pathological response or nonresponse after neoadjuvant ICI treatment. R-FMT mice yielded greater anti-tumor responses in combination with anti-PD-L1 treatment compared to NR-FMT, although the magnitude varied depending on mouse cell line, sex, and individual experiment. Detailed investigation of post-FMT mouse microbiota using 16S rRNA amplicon sequencing, with models to classify and correct for biological variables, revealed a shared presence of the most highly abundant taxa between the human inocula and mice, though low abundance human taxa colonized mice more variably after FMT. Multiple Clostridium species also correlated with tumor outcome in individual anti-PD-L1-treated R-FMT mice. RNAseq analysis revealed differential expression of T and NK cell-related pathways in responding tumors, irrespective of FMT source, with enrichment of these cell types confirmed by immunohistochemistry. This study identifies several human gut microbial species that may play a role in clinical responses to ICIs and suggests attention to biological variables is needed to improve reproducibility and limit variability across experimental murine cohorts.}, }
@article {pmid35211843, year = {2022}, author = {Shen, R and Ke, L and Li, Q and Dang, X and Shen, S and Shen, J and Li, S and Liang, L and Peng, B and Kuang, M and Ma, Y and Yang, Z and Hua, Y}, title = {Abnormal bile acid-microbiota crosstalk promotes the development of hepatocellular carcinoma.}, journal = {Hepatology international}, volume = {16}, number = {2}, pages = {396-411}, pmid = {35211843}, issn = {1936-0541}, support = {201707010387//Guangzhou Science, Technology and Innovation Commission/ ; 2014A020212626//Medical Science and Technology Foundation of Guangdong Province/ ; 81501677//National Natural Science Foundation of China/ ; 81873591//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Bile Acids and Salts ; *Carcinoma, Hepatocellular ; Humans ; *Liver Neoplasms/drug therapy ; Mice ; *Microbiota ; Vancomycin/pharmacology ; }, abstract = {BACKGROUND: Gut microbiota and microbe-derived metabolites are involved in the development of HCC. Bile acids (BAs) are the most important gut microbiota-modulated endogenous signaling molecules.<br><br>METHODS: We tested serum bile acid levels and gut microbiome compositions in patients with HCC, chemical-induced HCC mouse models (DEN-HCC mice) and mouse orthotopic implanted liver tumor models with vancomycin treatment (vancomycin-treated mice). Then, we screened an important kind of HCC-related BAs, and verified its effect on the growth of HCC in vivo and in vitro.<br><br>RESULTS: We found that the remarkably decreasing percentages of serum secondary BAs in the total bile acids of patients and DEN-HCC mice, especially, conjugated deoxycholic acids (DCA). The relative abundance of the bile salt hydrolase (BSH)-rich bacteria (Bifidobacteriales, Lactobacillales, Bacteroidales, and Clostridiales) was decreased in the feces of patients and DEN-HCC mice. Then, in vancomycin-treated mice, vancomycin treatment induced a reduction in the BSH-rich bacteria and promoted the growth of liver tumors. Similarly, the percentage of conjugated DCA after vancomycin treatment was significantly declined. We used a kind of conjugated DCA, Glyco-deoxycholic acid (GDCA), and found that GDCA remarkably inhibited the growth of HCC in vivo and in vitro.<br><br>CONCLUSIONS: We conclude that the remarkably decreasing percentages of serum conjugated DCA may be closely associated with HCC, which may be induced by the reducing gut BSH-rich bacteria. The mechanisms may be correlated with conjugated DCA directly inhibiting the growth and migration of HCC cells.}, }
@article {pmid35211537, year = {2022}, author = {Han, L and Azad, MAK and Huang, P and Wang, W and Zhang, W and Blachier, F and Kong, X}, title = {Maternal Supplementation With Different Probiotic Mixture From Late Pregnancy to Day 21 Postpartum: Consequences for Litter Size, Plasma and Colostrum Parameters, and Fecal Microbiota and Metabolites in Sows.}, journal = {Frontiers in veterinary science}, volume = {9}, number = {}, pages = {726276}, pmid = {35211537}, issn = {2297-1769}, abstract = {The present study determined the effects of different probiotic mixture supplementation to sows from late pregnancy to day 21 postpartum on reproductive performance, colostrum composition, plasma biochemical parameters, and fecal microbiota and metabolites. A total of 80 pregnant sows were randomly assigned to one of four groups (20 sows per group). The sows in the control group (CON group) were fed a basal diet, and those in the BS-A+B, BS-A+BL, and BS-B+BL groups were fed basal diets supplemented with 250 g/t of different probiotic mixture containing either 125 g/t of Bacillus subtilis A (BS-A), Bacillus subtilis B (BS-B), and/or Bacillus licheniformis (BL), respectively. The trial period was from day 85 of pregnancy to day 21 postpartum. The results showed that different dietary probiotic mixture supplementation increased (P < 0.05) the average weaning weight and average daily gain of piglets, while dietary BS-A+BL supplementation increased the number of weaned piglets (P < 0.05), litter weight (P = 0.06), litter weight gain (P = 0.06), and litter daily gain (P = 0.06) at weaning compared with the CON group. Different dietary probiotic mixture supplementation improved (P < 0.05) the colostrum quality by increasing the fat and dry matter concentrations, as well as the protein and urea nitrogen concentrations in the BS-A+BL group. Dietary probiotic mixture BS-B+BL increased the plasma total protein on days 1 and 21 postpartum while decreased the plasma albumin on day 1 postpartum (P < 0.05). In addition, the plasma high-density lipoprotein-cholesterol was increased in the BS-A+B and BS-B+BL groups on day 21 postpartum, while plasma ammonia was decreased in the BS-A+B and BS-A+BL groups on day 1 and in the three probiotic mixtures groups on day 21 postpartum (P < 0.05). Dietary supplementation with different probiotic mixture also modified the fecal microbiota composition and metabolic activity in sows during pregnancy and postpartum stages. Collectively, these findings suggest that maternal supplementation with Bacillus subtilis in combination with Bacillus licheniformis are promising strategies for improving the reproductive performance and the overall health indicators in sows, as well as the growth of their offspring.}, }
@article {pmid35209934, year = {2022}, author = {Fan, L and Ren, J and Chen, Y and Wang, Y and Guo, Z and Bu, P and Yang, J and Ma, W and Zhu, B and Zhao, Y and Cai, J}, title = {Effect of fecal microbiota transplantation on primary hypertension and the underlying mechanism of gut microbiome restoration: protocol of a randomized, blinded, placebo-controlled study.}, journal = {Trials}, volume = {23}, number = {1}, pages = {178}, pmid = {35209934}, issn = {1745-6215}, support = {81630014//national natural science foundation of china/ ; BJJWZYJH01201910023029//beijing outstanding young scientist program/ ; }, mesh = {Blood Pressure Monitoring, Ambulatory ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Hypertension/therapy ; Multicenter Studies as Topic ; Pulse Wave Analysis ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Hypertension is currently the leading modifiable cause of global morbidity and mortality, leading to substantial health and financial burdens. Although multiple studies of management models and innovative therapeutic strategies for hypertension have been conducted, there are still gaps in the field, with a poor control rate reflecting a lack of novel, effective, clinically translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between the microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between the gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention for treating hypertension is thus postulated, and fecal microbiota transplantation (FMT) from healthy donors was performed.<br><br>METHODS: A multicenter, randomized, placebo-controlled, blinded clinical trial will be performed in 120 grade 1 hypertensive patients for 3 months. All recruited patients will be randomly assigned in a 1:1 ratio to take oral FMT capsules or placebo capsules on day 1, day 7, and day 14 and will be followed up on day 30, day 60, and day 90. The primary outcome is the change in office systolic blood pressure from baseline to day 30. The main secondary outcomes are BP indicators, including changes in systolic and diastolic blood pressure from office and 24-h ambulatory blood pressure monitoring; assessments of ankle-branchial index and pulse wave velocity; profiling of fecal microbial composition and function; profiling of fecal and serum metabolome; changes in levels of blood glucose, blood lipids, and body mass index; and assessment of adverse events as a measure of safety.<br><br>DISCUSSION: Expanding upon our previous research on the role of the gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and explores the potential of fecal microbiota transplantation for treating hypertension. The underlying mechanisms, particularly the roles of specific microorganisms or their postbiotics in blood pressure amelioration, will also be investigated via multiple approaches, such as metagenomic sequencing and metabolomic profiling.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT04406129 . Registered on May 28, 2020.}, }
@article {pmid35208740, year = {2022}, author = {Di Pilato, V and Morecchiato, F and Rizzato, C and Quaranta, G and Fais, R and Gandolfo, C and Antonelli, A and Cusi, MG and Pistello, M and Rossolini, GM and Sanguinetti, M and Lupetti, A and Masucci, L}, title = {Validation of Two Commercial Multiplex Real-Time PCR Assays for Detection of SARS-CoV-2 in Stool Donors for Fecal Microbiota Transplantation.}, journal = {Microorganisms}, volume = {10}, number = {2}, pages = {}, pmid = {35208740}, issn = {2076-2607}, abstract = {Recurrent infection by Clostridioides difficile has recently been treated by fecal microbiota transplantation (FMT). As viable SARS-CoV-2 was recovered from stool of asymptomatic individuals, the FMT procedure could be a potential risk of SARS-CoV-2 transmission, thus underlying the need to reliably detect SARS-CoV-2 in stool. Here, we performed a multicentric study to explore performances of two commercially available assays for detection of SARS-CoV-2 RNA in stool of potential FMT donors. In three hospitals, 180 stool samples were spiked with serial 10-fold dilutions of a SARS-CoV-2 inactivated lysate to evaluate the Seegene Allplex™ SARS-CoV-2 (SC2) and SARS-CoV-2/FluA/FluB/RSV (SC2FABR) Assays for the detection of viral RNA in stool of FMT donors. The results revealed that both assays detected down to 2 TCID50/mL with comparable limit of detection values, SC2 showing more consistent target positivity rate than SC2FABR. Beyond high amplification efficiency, correlation between CT values and log concentrations of inactivated viral lysates showed R[2] values ranging from 0.88 to 0.90 and from 0.87 to 0.91 for the SC2 and SC2FABR assay, respectively. The present results demonstrate that both methods are highly reproducible, sensitive, and accurate for SARS-CoV-2 RNA detection in stool, suggesting a potential use in FMT-donor screening.}, }
@article {pmid35207328, year = {2022}, author = {Zhang, X and Ishikawa, D and Nomura, K and Fukuda, N and Haraikawa, M and Haga, K and Shibuya, T and Mita, T and Nagahara, A}, title = {Donor Screening Revisions of Fecal Microbiota Transplantation in Patients with Ulcerative Colitis.}, journal = {Journal of clinical medicine}, volume = {11}, number = {4}, pages = {}, pmid = {35207328}, issn = {2077-0383}, support = {JP16K09328//KAKENHI/ ; Kyowa Kirin Co., Ltd.,//Kyowa Kirin Co., Ltd.,/ ; Kyowa Hakko Bio Co.,//Kyowa Hakko Bio Co.,/ ; Kirin Holdings Co., Ltd.//Kirin Holdings Co., Ltd./ ; }, abstract = {Fecal microbiota transplantation (FMT) has been recognized as a promising treatment for dysbiosis-related diseases. Since 2014, FMT has been utilized to treat ulcerative colitis (UC) in our clinical studies and has shown efficacy and safety. As donor screening (DS) is the primary step to ensure the safety of FMT, we report our experience with DS and present the screening results to improve the prospective DS criteria and provide references for future studies. The donor candidates were screened according to the DS criteria. The first DS criteria were proposed in June 2014 and revised substantially in May 2018. We further sorted the screening results and costs of laboratory tests. From June 2014 to April 2018, the DS eligibility rate was 50%. The total laboratory testing cost for each candidate was JPY 17,580/USD 160.21. From May 2018 to September 2021, the DS eligibility rate was 25.6%. The total laboratory testing cost for each candidate was JPY 40,740/USD 371.36. The reduction in donor eligibility rates due to more stringent criteria should be considered for cost and safety. Studies must consider the latest updates and make timely modifications in the DS criteria to ensure patient safety.}, }
@article {pmid35203709, year = {2022}, author = {Panther, EJ and Dodd, W and Clark, A and Lucke-Wold, B}, title = {Gastrointestinal Microbiome and Neurologic Injury.}, journal = {Biomedicines}, volume = {10}, number = {2}, pages = {}, pmid = {35203709}, issn = {2227-9059}, abstract = {Communication between the enteric nervous system (ENS) of the gastrointestinal (GI) tract and the central nervous system (CNS) is vital for maintaining systemic homeostasis. Intrinsic and extrinsic neurological inputs of the gut regulate blood flow, peristalsis, hormone release, and immunological function. The health of the gut microbiome plays a vital role in regulating the overall function and well-being of the individual. Microbes release short-chain fatty acids (SCFAs) that regulate G-protein-coupled receptors to mediate hormone release, neurotransmitter release (i.e., serotonin, dopamine, noradrenaline, γ-aminobutyric acid (GABA), acetylcholine, and histamine), and regulate inflammation and mood. Further gaseous factors (i.e., nitric oxide) are important in regulating inflammation and have a response in injury. Neurologic injuries such as ischemic stroke, spinal cord injury, traumatic brain injury, and hemorrhagic cerebrovascular lesions can all lead to gut dysbiosis. Additionally, unfavorable alterations in the composition of the microbiota may be associated with increased risk for these neurologic injuries due to increased proinflammatory molecules and clotting factors. Interventions such as probiotics, fecal microbiota transplantation, and oral SCFAs have been shown to stabilize and improve the composition of the microbiome. However, the effect this has on neurologic injury prevention and recovery has not been studied extensively. The purpose of this review is to elaborate on the complex relationship between the nervous system and the microbiome and to report how neurologic injury modulates the status of the microbiome. Finally, we will propose various interventions that may be beneficial in the recovery from neurologic injury.}, }
@article {pmid35202891, year = {2022}, author = {Alonso, CD and Maron, G and Kamboj, M and Carpenter, PA and Gurunathan, A and Mullane, KM and Dubberke, ER}, title = {American Society for Transplantation and Cellular Therapy Series: #5-Management of Clostridioides difficile Infection in Hematopoietic Cell Transplant Recipients.}, journal = {Transplantation and cellular therapy}, volume = {28}, number = {5}, pages = {225-232}, doi = {10.1016/j.jtct.2022.02.013}, pmid = {35202891}, issn = {2666-6367}, mesh = {Adult ; Cell- and Tissue-Based Therapy ; Child ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Transplant Recipients ; United States/epidemiology ; }, abstract = {The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy partnered with its Transplant Infectious Disease Special Interest Group to update its 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A completely new approach was taken with the goal of better serving clinical providers by publishing each standalone topic in the infectious disease series as a concise format of frequently asked questions (FAQ), tables, and figures. Adult and pediatric infectious disease and HCT content experts developed and then answered FAQs and finalized topics with harmonized recommendations that were made by assigning an A through E strength of recommendation paired with a level of supporting evidence graded I through III. This fifth guideline in the series focuses on Clostridioides difficile infection with FAQs that address the prevalence, incidence, clinical features, colonization versus infection, clinical complications, diagnostic considerations, pharmacological therapies for episodic or recurrent infection, and the roles of prophylactic antibiotics, probiotics, and fecal microbiota transplantation.}, }
@article {pmid35202290, year = {2022}, author = {Isidori, M and Corbee, RJ and Trabalza-Marinucci, M}, title = {Nonpharmacological Treatment Strategies for the Management of Canine Chronic Inflammatory Enteropathy-A Narrative Review.}, journal = {Veterinary sciences}, volume = {9}, number = {2}, pages = {}, pmid = {35202290}, issn = {2306-7381}, abstract = {Chronic inflammatory enteropathy (CIE) refers to a heterogeneous group of idiopathic diseases of the dog characterised by persistent gastrointestinal (GI) clinical signs. If conventional dietary treatment alone would be unsuccessful, management of CIE is traditionally attained by the use of pharmaceuticals, such as antibiotics and immunosuppressive drugs. While being rather effective, however, these drugs are endowed with side effects, which may impact negatively on the animal's quality of life. Therefore, novel, safe and effective therapies for CIE are highly sought after. As gut microbiota imbalances are often associated with GI disorders, a compelling rationale exists for the use of nonpharmacological methods of microbial manipulation in CIE, such as faecal microbiota transplantation and administration of pre-, pro-, syn- and postbiotics. In addition to providing direct health benefits to the host via a gentle modulation of the intestinal microbiota composition and function, these treatments may also possess immunomodulatory and epithelial barrier-enhancing actions. Likewise, intestinal barrier integrity, along with mucosal inflammation, are deemed to be two chief therapeutic targets of mesenchymal stem cells and selected vegetable-derived bioactive compounds. Although pioneering studies have revealed encouraging findings regarding the use of novel treatment agents in CIE, a larger body of research is needed to address fully their mode of action, efficacy and safety.}, }
@article {pmid35201766, year = {2022}, author = {Lu, X and Jing, Y and Zhang, N and Cao, Y}, title = {Eurotium cristatum, a Probiotic Fungus from Fuzhuan Brick Tea, and Its Polysaccharides Ameliorated DSS-Induced Ulcerative Colitis in Mice by Modulating the Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {70}, number = {9}, pages = {2957-2967}, doi = {10.1021/acs.jafc.1c08301}, pmid = {35201766}, issn = {1520-5118}, mesh = {Animals ; Aspergillus ; *Colitis ; *Colitis, Ulcerative/chemically induced/drug therapy/genetics ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; Fungi/genetics ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Polysaccharides/pharmacology ; *Probiotics ; RNA, Ribosomal, 16S ; Tea ; }, abstract = {Eurotium cristatum is a potential probiotic fungus that is used to enhance Fuzhuan tea quality through fermentation and could reduce obesity by modulating gut dysbiosis. This study aimed to investigate the effects and possible mechanisms of killed E. cristatum (KEC) and its polysaccharides (ECP) in ulcerative colitis (UC) relief. KEC and ECP were administered to mice with dextran sulfate sodium-induced UC. The results showed that UC severity, intestinal inflammation, and tight junction protein levels were greatly improved. Furthermore, 16S rRNA sequencing results showed that Escherichia coli, Enterococcus faecium, Clostridium perfringens, Bacteroides caccae, Rothia aeria, and Prevotella melaninogenica were depleted, while Alistipes finegoldii and Bacteroides stercorirosoris were enriched. A fecal microbial transplantation trial confirmed that KEC and ECP ameliorated UC by regulating gut dysbiosis. Thus, this research suggests that KEC and ECP are novel, potent, food-based anti-inflammatory agents that relieve UC by modulating gut dysbiosis.}, }
@article {pmid35200660, year = {2022}, author = {Hayashi, K and Komatsu, S and Kuno, H and Asai, S and Matsuura, I and Kudkyal, VR and Kawahara, T}, title = {Virucidal and Immunostimulating Activities of Monogalactosyl Diacylglyceride from Coccomyxa sp. KJ, a Green Microalga, against Murine Norovirus and Feline Calicivirus.}, journal = {Marine drugs}, volume = {20}, number = {2}, pages = {}, pmid = {35200660}, issn = {1660-3397}, support = {JPMJTR204H//Japan Science and Technology Agency/ ; JPMJMI9D4//Japan Science and Technology Agency/ ; }, mesh = {Animals ; Antibodies, Neutralizing/blood ; Antiviral Agents/administration &amp; dosage/isolation &amp; purification/*pharmacology ; Caliciviridae Infections/*drug therapy/virology ; Calicivirus, Feline/drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Galactolipids/administration &amp; dosage/isolation &amp; purification/*pharmacology ; Mice ; Mice, Inbred BALB C ; Microalgae/*metabolism ; Norovirus/drug effects ; Time Factors ; Virus Shedding/drug effects ; }, abstract = {Human noroviruses are the most common pathogens causing acute gastroenteritis and may lead to more severe illnesses among immunosuppressed people, including elderly and organ transplant recipients. To date, there are no safe and effective vaccines or antiviral agents for norovirus infections. In the present study, we aimed to demonstrate the antiviral activity of monogalactosyl diacylglyceride (MGDG) isolated from a microalga, Coccomyxa sp. KJ, against murine norovirus (MNV) and feline calicivirus (FCV), the surrogates for human norovirus. MGDG showed virucidal activities against these viruses in a dose- and time-dependent manner-MGDG at 100 μg/mL reduced the infectivity of MNV and FCV to approximately 10% after 60 min incubation. In the animal experiments of MNV infection, intraoral administration of MGDG (1 mg/day) exerted a therapeutic effect by suppressing viral shedding in the feces and produced high neutralizing antibody titers in sera and feces. When MGDG was orally administered to immunocompromised mice treated with 5-fluorouracil, the compound exhibited earlier stopping of viral shedding and higher neutralizing antibody titers of sera than those in the control mice administered with distilled water. Thus, MGDG may offer a new therapeutic and prophylactic alternative against norovirus infections.}, }
@article {pmid35199405, year = {2022}, author = {Singh, V and Ahlawat, S and Mohan, H and Gill, SS and Sharma, KK}, title = {Balancing reactive oxygen species generation by rebooting gut microbiota.}, journal = {Journal of applied microbiology}, volume = {132}, number = {6}, pages = {4112-4129}, doi = {10.1111/jam.15504}, pmid = {35199405}, issn = {1365-2672}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases ; *Probiotics ; Reactive Oxygen Species ; }, abstract = {Reactive oxygen species (ROS; free radical form O2 [•-] , superoxide radical; OH[•] , hydroxyl radical; ROO[•] , peroxyl; RO[•] , alkoxyl and non-radical form [1] O2 , singlet oxygen; H2 O2 , hydrogen peroxide) are inevitable companions of aerobic life with crucial role in gut health. But, overwhelming production of ROS can cause serious damage to biomolecules. In this review, we have discussed several sources of ROS production that can be beneficial or dangerous to the human gut. Micro-organisms, organelles and enzymes play crucial role in ROS generation, where NOX1 is the main intestinal enzyme, which produce ROS in the intestine epithelial cells. Previous studies have reported that probiotics play significant role in gut homeostasis by checking the ROS generation, maintaining the antioxidant level, immune system and barrier protection. With current knowledge, we have critically analysed the available literature and presented the outcome in the form of bubble maps to suggest that the probiotics help in controlling the ROS-specific intestinal diseases, such as inflammatory bowel disease (IBD) and colon cancer. Finally, it has been concluded that rebooting of the gut microbiota with probiotics, postbiotics or faecal microbiota transplantation (FMT) can have crucial implications in the structuring of gut communities for the personalized management of the gastrointestinal (GI) diseases.}, }
@article {pmid35196976, year = {2023}, author = {Ahmed, LA and Al-Massri, KF}, title = {Gut Microbiota Modulation for Therapeutic Management of Various Diseases: A New Perspective Using Stem Cell Therapy.}, journal = {Current molecular pharmacology}, volume = {16}, number = {1}, pages = {43-59}, doi = {10.2174/1874467215666220222105004}, pmid = {35196976}, issn = {1874-4702}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis/therapy ; Anti-Bacterial Agents ; Regenerative Medicine ; Cell- and Tissue-Based Therapy ; }, abstract = {Dysbiosis has been linked to various diseases ranging from cardiovascular, neurologic, gastrointestinal, respiratory, and metabolic illnesses to cancer. Restoring of gut microbiota balance represents an outstanding clinical target for the management of various multidrug-resistant diseases. Preservation of gut microbial diversity and composition could also improve stem cell therapy which now has diverse clinical applications in the field of regenerative medicine. Gut microbiota modulation and stem cell therapy may be considered a highly promising field that could add up towards the improvement of different diseases, increasing the outcome and efficacy of each other through mutual interplay or interaction between both therapies. Importantly, more investigations are required to reveal the cross-talk between microbiota modulation and stem cell therapy to pave the way for the development of new therapies with enhanced therapeutic outcomes. This review provides an overview of dysbiosis in various diseases and their management. It also discusses microbiota modulation via antibiotics, probiotics, prebiotics, and fecal microbiota transplant to introduce the concept of dysbiosis correction for the management of various diseases. Furthermore, we demonstrate the beneficial interactions between microbiota modulation and stem cell therapy as a way for the development of new therapies in addition to limitations and future challenges regarding the applications of these therapies.}, }
@article {pmid35196629, year = {2022}, author = {Bi, W and Cai, S and Hang, Z and Lei, T and Wang, D and Wang, L and Du, H}, title = {Transplantation of feces from mice with Alzheimer's disease promoted lung cancer growth.}, journal = {Biochemical and biophysical research communications}, volume = {600}, number = {}, pages = {67-74}, doi = {10.1016/j.bbrc.2022.01.078}, pmid = {35196629}, issn = {1090-2104}, mesh = {*Alzheimer Disease/pathology ; Animals ; Feces ; *Lung Neoplasms ; Mice ; Proto-Oncogene Proteins c-akt ; RNA, Ribosomal, 16S ; bcl-2-Associated X Protein ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurologic disorder that causes the brain to shrink and brain cells to die. Lung cancer is characterized by high morbidity and mortality, late diagnosis and poor prognosis. And there is no specific mechanism to explain the epidemiological correlation between AD and lung cancer.<br><br>MATERIALS AND METHODS: Lewis lung cancer cells (LLC) were injected into the left forelimb armpit of APP/PS1 mice to establish a tumor-bearing model. After remodeling the gut microbiota by fecal microbiota transplantation (FMT), the tumor were collected and analyzed for tumor size, Western blotting, and 16S rRNA gene sequencing.<br><br>RESULTS: Compared with the control group, the AD FMT group showed larger tumors, while C57 FMT group showed smaller tumors. The former group showed the inhibition of AKT/Bax/Bcl-2 pathway, while the latter showed promotion of Caspase-1/IL-1&#x3b2; and AKT/Bax/Bcl-2 pathway, which induced changes in tumor size. And Prevotella, Prevotella, Mucispirillum and Halomonas in the gut lumen of LLC tumor-bearing mice are increased, and Bacteroides, Coprobacillus, Bifidobacterium, Faecalibacterium and Aggregatiacter are decreased significantly.<br><br>CONCLUSION: AD and lung cancer showed a positive correlation in APP expression, which proposed a different view from epidemiology on the correlation between AD and lung cancer.}, }
@article {pmid35195774, year = {2022}, author = {Shi, Q and Dai, L and Zhao, Q and Zhang, X}, title = {A review on the effect of gut microbiota on metabolic diseases.}, journal = {Archives of microbiology}, volume = {204}, number = {3}, pages = {192}, pmid = {35195774}, issn = {1432-072X}, support = {32101368//National Natural Science Foundation of China/ ; 2020JJ5709//Natural Science Foundation of Hunan Province/ ; 2021-50//Science and Technology Plan Project for Natural Resources of Hunan Province/ ; }, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Metabolic Diseases/microbiology ; *Probiotics ; }, abstract = {Human gut microbiota are a huge and complex microbial community, which is recognized to play a significant role in regulating host metabolism. However, the destruction of gut microbiota leads to the pathological response of host, and thus results in a variety of metabolic diseases. This article gives a brief review of research progress on gut microbiota and some main metabolic diseases, including osteoporosis, obesity, type 2 diabetes, non-alcoholic fatty liver, and hypertension, with a specific focus on the effect of gut microbiota on diseases' occurrence and development. In addition, this review article also shows some case studies on the regulation of gut microbiota by new means, such as fecal microbiota transplantation and oral probiotics. Although gut microbiota are considered as a promising novel target for the treatment of metabolic diseases, it is also necessary to encourage further studies to provide more valuable data for guiding the application of gut microbiota on disease therapy in future.}, }
@article {pmid35193638, year = {2022}, author = {Stallmach, A and Grunert, P and Stallhofer, J and Löffler, B and Baier, M and Rödel, J and Kiehntopf, M and Neugebauer, S and Pieper, DH and Junca, H and Tannapfel, A and Merkel, U and Schumacher, U and Breternitz-Gruhne, M and Heller, T and Schauer, A and Hartmann, M and Steube, A}, title = {Transfer of FRozen Encapsulated multi-donor Stool filtrate for active ulcerative Colitis (FRESCO): study protocol for a prospective, multicenter, double-blind, randomized, controlled trial.}, journal = {Trials}, volume = {23}, number = {1}, pages = {173}, pmid = {35193638}, issn = {1745-6215}, support = {01KG1814//Bundesministerium f&#xfc;r Bildung und Forschung/ ; }, mesh = {*Colitis, Ulcerative/diagnosis/therapy ; Double-Blind Method ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces ; Humans ; Multicenter Studies as Topic ; Prospective Studies ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with significant morbidity and mortality. Although the precise cause remains unknown, disturbances in the intestinal microbial community have been linked to its pathogenesis. Randomized controlled trials in UC and relapsing Clostridioides difficile infection (CDI) have established fecal microbiota (FM) transfer (FMT) as an effective therapy. In this context, preliminary results indicated that the transfer of sterile fecal microbiota filtrates (<0.2 μm; FMF, FMFT) of donor stool also drives gastrointestinal microbiota changes and eliminates symptoms in CDI patients. However, along with the success of FMT, regulatory agencies issued safety alerts following reports of serious adverse events due to transmission of enteric pathogens through FMT. To reduce this risk, we established an extensive test protocol for our donors and quarantine regulations for the produced capsules, but alternative concepts are desirable.<br><br>METHODS: Our project is a randomized, controlled, longitudinal, prospective, three-arm, multicenter, double-blind study to determine the safety and efficacy of repeated long-term, multi-donor FM or FMF transfers compared to placebo using oral, frozen capsules in 174 randomized patients with mild to moderate active UC. The primary outcome will be clinical remission at week 12.<br><br>DISCUSSION: This proposal aims to examine (a) the efficacy of encapsulated transfer of FM and FMF as a therapy for mild to moderate UC, (b) the short- and long-term safety of FMT and FMFT in patients with UC, and (c) the microbial and immunologic changes that occur after FMT and FMFT to help understand how and why it affects inflammatory bowel disease.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT03843385 . DRKS (Deutsches Register f&#xfc;r Klinische Studien) DRKS00020471.}, }
@article {pmid35191819, year = {2022}, author = {Liang, H and Song, H and Zhang, X and Song, G and Wang, Y and Ding, X and Duan, X and Li, L and Sun, T and Kan, Q}, title = {Metformin attenuated sepsis-related liver injury by modulating gut microbiota.}, journal = {Emerging microbes &amp; infections}, volume = {11}, number = {1}, pages = {815-828}, pmid = {35191819}, issn = {2222-1751}, mesh = {Animals ; *Gastrointestinal Microbiome ; Liver ; *Metformin/pharmacology/therapeutic use ; RNA, Ribosomal, 16S/genetics ; Rats ; *Sepsis/complications/drug therapy/microbiology ; }, abstract = {Increased evidence shows that gut microbiota acts as the primary regulator of the liver; however, its role in sepsis-related liver injury (SLI) in the elderly is unclear. This study assessed whether metformin could attenuate SLI by modulating gut microbiota in septic-aged rats. Cecal ligation and puncture (CLP) was used to induce SLI in aged rats. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. The composition of gut microbiota was analysed by 16S rRNA sequencing. Moreover, the liver and colon tissues were analysed by histopathology, immunofluorescence, immunohistochemistry, and reverse transcription polymerase chain reaction (RT-PCR). Metformin improved liver damage, colon barrier dysfunction in aged SLI rats. Moreover, metformin improved sepsis-induced liver inflammation and damage under gut microbiota. Importantly, FMT assay showed that rats gavaged with faeces from metformin-treated SLI rats displayed less severe liver damage and colon barrier dysfunctions than those gavaged with faeces from SLI rats. The gut microbiota composition among the sham-operated, CLP-operated and metformin-treated SLI rats was different. In particular, the proportion of Klebsiella and Escherichia_Shigella was higher in SLI rats than sham-operated and metformin-treated SLI rats; while metformin could increase the proportion of Bifidobacterium, Muribaculaceae, Parabacteroides_distasonis and Alloprevitella in aged SLI rats. Additionally, Klebsiella and Escherichia_Shigella correlated positively with the inflammatory factors in the liver. Our findings suggest that metformin may improve liver injury by regulating the gut microbiota and alleviating colon barrier dysfunction in septic-aged rats, which may be an effective therapy for SLI.}, }
@article {pmid35188867, year = {2022}, author = {Pieters, W and Hugenholtz, F and Kos, K and Cammeraat, M and Moliej, TC and Kaldenbach, D and Klarenbeek, S and Davids, M and Drost, L and de Konink, C and Delzenne-Goette, E and de Visser, KE and Te Riele, H}, title = {Pro-mutagenic effects of the gut microbiota in a Lynch syndrome mouse model.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2035660}, pmid = {35188867}, issn = {1949-0984}, mesh = {Animals ; *Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis/genetics/pathology ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Mice ; MutS Homolog 2 Protein/genetics ; Mutagenesis ; Mutagens ; }, abstract = {The gut microbiota strongly impacts the development of sporadic colorectal cancer (CRC), but it is largely unknown how the microbiota affects the pathogenesis of mismatch-repair-deficient CRC in the context of Lynch syndrome. In a mouse model for Lynch syndrome, we found a nearly complete loss of intestinal tumor development when animals were transferred from a conventional "open" animal facility to specific-pathogen-free (SPF) conditions. Using 16S sequencing we detected large changes in microbiota composition between the two facilities. Transcriptomic analyses of tumor-free intestinal tissues showed signs of strong intestinal inflammation in conventional mice. Whole exome sequencing of tumors developing in Msh2-Lynch mice revealed a much lower mutational load in the single SPF tumor than in tumors developing in conventional mice, suggesting reduced epithelial proliferation in SPF mice. Fecal microbiota transplantations with conventional feces altered the immune landscape and gut homeostasis, illustrated by increased gut length and elevated epithelial proliferation and migration. This was associated with drastic changes in microbiota composition, in particular increased relative abundances of different mucus-degrading taxa such as Desulfovibrio and Akkermansia, and increased bacterial-epithelial contact. Strikingly, transplantation of conventional microbiota increased microsatellite instability in untransformed intestinal epithelium of Msh2-Lynch mice, indicating that the composition of the microbiota influences the rate of mutagenesis in MSH2-deficient crypts.}, }
@article {pmid35188712, year = {2022}, author = {Wang, Y and Shi, Y and Li, W and Wang, S and Zheng, J and Xu, G and Li, G and Shen, X and Yang, J}, title = {Gut microbiota imbalance mediates intestinal barrier damage in high-altitude exposed mice.}, journal = {The FEBS journal}, volume = {289}, number = {16}, pages = {4850-4868}, doi = {10.1111/febs.16409}, pmid = {35188712}, issn = {1742-4658}, mesh = {Altitude ; Animals ; Anti-Bacterial Agents/pharmacology ; *Gastrointestinal Microbiome ; Intestines ; Mice ; Mice, Inbred C57BL ; }, abstract = {The environmental conditions in high-altitude areas can induce gastrointestinal disorders and changes in gut microbiota. The gut microbiota is closely related to a variety of gastrointestinal diseases, although the underlying pathogenic mechanisms are not well-identified. The present study aimed to investigate the regulatory effect of high altitude on intestinal dysfunction via gut microbiota disturbance. Forty C57BL/6J mice were divided into four groups: one plain control group (CON) and three high-altitude exposure groups (HAE) (altitude: 4000 m a.s.l.; oxygen content: 12.7%; 1-, 2- and 4-week exposure). Another set of 40 mice was divided into two CON and two HAE subgroups. Antibiotic cocktails were administered to one CON and HAE groups and autoclaved water was administered to the second CON and HAE groups for 4 weeks, respectively. In the fecal microbiota transplantation experiment, there were four transplantation groups, which received, respectively: phosphate-buffered saline for 2 weeks, feces from CON for 2 weeks, feces from HAE-4W for 2 weeks, and HAE-4W for 4 weeks. Hematoxylin and eosin staining, periodic acid-Schiff staining, a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and a quantitative reverse transcriptase-polymerase chain reaction were applied to detect changes in intestinal cellular structure, morphology, apoptosis and intestinal inflammatory response. Fecal microbiota was analyzed using 16S rDNA amplicon sequencing. A high-altitude environment changed the ecological balance of gut microbiota in mice and caused damage to the intestinal structure and mucosal barrier. Interestingly, similar damage, which was inhibited by antibiotic cocktails at high altitude, was observed in mice transplanted with fecal microbiota from HAE. A high-altitude environment contributes to dyshomeostasis of gut microbiota, thereby impairing the intestinal mucosal barrier, eventually inducing and exacerbating intestinal damage.}, }
@article {pmid35185934, year = {2022}, author = {Zhong, Y and Cao, J and Ma, Y and Zhang, Y and Liu, J and Wang, H}, title = {Fecal Microbiota Transplantation Donor and Dietary Fiber Intervention Collectively Contribute to Gut Health in a Mouse Model.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {842669}, pmid = {35185934}, issn = {1664-3224}, mesh = {Animals ; Bacteria/*classification/genetics ; Dietary Fiber/*administration &amp; dosage ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Male ; Mice ; Swine ; }, abstract = {Transforming the gut microbiota has turned into the most intriguing target for interventions in multiple gastrointestinal and non-gastrointestinal disorders. Fecal microbiota transplantation (FMT) is a therapeutic tool that administers feces collected from healthy donors into patients to help replenish the gut microbial balance. Considering the random donor selection, to maintain the optimal microbial ecosystem, post-FMT is critical for therapy outcomes but challenging. Aiming to study the interventions of different diets on recipients' gut microbiota post-FMT that originated from donors with different diets, we performed FMT from domestic vs. wild pigs that are living on low-fiber vs. high-fiber diets into the pseudo-GF mouse, followed with fiber-free (FF) or fiber-rich (FR) diets post-FMT. Different patterns of gut microbiota and metabolites were observed when mice FMT from different donors were paired with different dietary fiber contents. Enrichment of bacteria, including Akkermansia and Parabacteroides, together with alteration of metabolites, including palmitic acid, stearic acid, and nicotinic acid, was noted to improve crypt length and mucus layer in the gut in mice FMT from wild pigs fed an FR diet. The results provide novel insight into the different responses of reconstructed gut microbiota by FMT to dietary fiber. Our study highlighted the importance of post-FMT precise dietary interventions.}, }
@article {pmid35185849, year = {2022}, author = {Mousa, WK and Chehadeh, F and Husband, S}, title = {Recent Advances in Understanding the Structure and Function of the Human Microbiome.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {825338}, pmid = {35185849}, issn = {1664-302X}, abstract = {Trillions of microbes live within our bodies in a deep symbiotic relationship. Microbial populations vary across body sites, driven by differences in the environment, immunological factors, and interactions between microbial species. Major advances in genome sequencing enable a better understanding of microbiome composition. However, most of the microbial taxa and species of the human microbiome are still unknown. Without revealing the identity of these microbes as a first step, we cannot appreciate their role in human health and diseases. A shift in the microbial balance, termed dysbiosis, is linked to a broad range of diseases from simple colitis and indigestion to cancer and dementia. The last decade has witnessed an explosion in microbiome research that led to a better understanding of the microbiome structure and function. This understanding leads to potential opportunities to develop next-generation microbiome-based drugs and diagnostic biomarkers. However, our understanding is limited given the highly personalized nature of the microbiome and its complex and multidirectional interactions with the host. In this review, we discuss: (1) our current knowledge of microbiome structure and factors that shape the microbial composition, (2) recent associations between microbiome dysbiosis and diseases, and (3) opportunities of new microbiome-based therapeutics. We analyze common themes, promises, gaps, and challenges of the microbiome research.}, }
@article {pmid35185631, year = {2021}, author = {Puricelli, C and Rolla, R and Gigliotti, L and Boggio, E and Beltrami, E and Dianzani, U and Keller, R}, title = {The Gut-Brain-Immune Axis in Autism Spectrum Disorders: A State-of-Art Report.}, journal = {Frontiers in psychiatry}, volume = {12}, number = {}, pages = {755171}, pmid = {35185631}, issn = {1664-0640}, abstract = {The interest elicited by the large microbial population colonizing the human gut has ancient origins and has gone through a long evolution during history. However, it is only in the last decades that the introduction of high-throughput technologies has allowed to broaden this research field and to disentangle the numerous implications that gut microbiota has in health and disease. This comprehensive ecosystem, constituted mainly by bacteria but also by fungi, parasites, and viruses, is proven to be involved in several physiological and pathological processes that transcend the intestinal homeostasis and are deeply intertwined with apparently unrelated body systems, such as the immune and the nervous ones. In this regard, a novel speculation is the relationship between the intestinal microbial flora and the pathogenesis of some neurological and neurodevelopmental disorders, including the clinical entities defined under the umbrella term of autism spectrum disorders. The bidirectional interplay has led researchers to coin the term gut-brain-immune system axis, subverting the theory of the brain as an immune-privileged site and underscoring the importance of this reciprocal influence already from fetal life and especially during the pre- and post-natal neurodevelopmental process. This revolutionary theory has also unveiled the possibility to modify the gut microbiota as a way to treat and even to prevent different kinds of pathologies. In this sense, some attempts have been made, ranging from probiotic administration to fecal microbiota transplantation, with promising results that need further elaboration. This state-of-art report will describe the main aspects regarding the human gut microbiome and its specific role in the pathogenesis of autism and its related disorders, with a final discussion on the therapeutic and preventive strategies aiming at creating a healthy intestinal microbial environment, as well as their safety and ethical implications.}, }
@article {pmid35184756, year = {2022}, author = {Islam, J and Tanimizu, M and Shimizu, Y and Goto, Y and Ohtani, N and Sugiyama, K and Tatezaki, E and Sato, M and Makino, E and Shimada, T and Ueda, C and Matsuo, A and Suyama, Y and Sakai, Y and Furukawa, M and Usami, K and Yoneyama, H and Aso, H and Tanaka, H and Nochi, T}, title = {Development of a rational framework for the therapeutic efficacy of fecal microbiota transplantation for calf diarrhea treatment.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {31}, pmid = {35184756}, issn = {2049-2618}, mesh = {Animals ; Cattle ; *Diarrhea/microbiology/therapy ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {BACKGROUND: Establishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of the differences in farm management practices, the lack of optimal donors, and recipient selection. In this study, the underlying factors of successful and unsuccessful FMT treatment cases are elucidated, and the potential markers for predicting successful FMT are identified using fecal metagenomics via 16S rRNA gene sequencing, fecal metabolomics via capillary electrophoresis time-of-flight mass spectrometry, and machine learning approaches.<br><br>RESULTS: Specifically, 20 FMT treatment cases, in which feces from healthy donors were intrarectally transferred into recipient diarrheal calves, were conducted with a success rate of 70%. Selenomonas was identified as a microorganism genus that showed significant donor-recipient compatibility in successful FMT treatments. A strong positive correlation between the microbiome and metabolome data, which is a prerequisite factor for FMT success, was confirmed by Procrustes analysis in successful FMT (r = 0.7439, P = 0.0001). Additionally, weighted gene correlation network analysis confirmed the positively or negatively correlated pairs of bacterial taxa (family Veillonellaceae) and metabolomic features (i.e., amino acids and short-chain fatty acids) responsible for FMT success. Further analysis aimed at establishing criteria for donor selection identified the genus Sporobacter as a potential biomarker in successful donor selection. Low levels of metabolites, such as glycerol 3-phosphate, dihydroxyacetone phosphate, and isoamylamine, in the donor or recipients prior to FMT, are predicted to facilitate FMT.<br><br>CONCLUSIONS: Overall, we provide the first substantial evidence of the factors related to FMT success or failure; these findings could improve the design of future microbial therapeutics for treating diarrhea in calves. Video abstract.}, }
@article {pmid35184054, year = {2022}, author = {Okafuji, H and Iida, N and Kitamura, K and Seishima, J and Wang, Z and Yutani, M and Yoshio, T and Yamashita, T and Sakai, Y and Honda, M and Yamashita, T and Fujinaga, Y and Shinkura, R and Hamaguchi, Y and Mizukoshi, E and Kaneko, S}, title = {Oral Corticosteroids Impair Mucin Production and Alter the Posttransplantation Microbiota in the Gut.}, journal = {Digestion}, volume = {103}, number = {4}, pages = {269-286}, doi = {10.1159/000522039}, pmid = {35184054}, issn = {1421-9867}, mesh = {Adrenal Cortex Hormones ; Animals ; *Colitis, Ulcerative/therapy ; Feces ; Inflammation ; Mice ; *Microbiota ; Mucins ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {INTRODUCTION: Gut microbiota alterations cause inflammation in patients with ulcerative colitis (UC). Fecal microbiota transplantation (FMT) enables manipulating the microbiota's composition, but the mechanisms underlying colonization of the posttransplantation microbiota are poorly understood.<br><br>METHODS: In this open-label, nonrandomized study, the FMT efficacy and changes in the gut microbiota were evaluated in 8 UC patients with mild-to-moderately active endoscopic colonic lesions. Compositional changes in the fecal and mucosal microbiotas between donors and recipients were examined via 16S rRNA-based sequencing. To investigate the effects of oral corticosteroids on microbiota colonization, FMT was performed in germ-free prednisolone (PSL)-administered mice to examine the factors determining colonization.<br><br>RESULTS: Four UC patients achieved clinical remission (CR) after FMT, and 3 also achieved endoscopic remission. The fecal microbiotas of the CR patients changed similar to those of the donors after FMT. The mucin-coding gene, MUC2, was less expressed in the colons of the PSL-dependent patients than in the PSL-free patients. In the mice, PSL treatment decreased the fecal mucin production and altered the posttransplantation fecal microbiota composition. Adding either exogenous mucin or the mucin secretagogue, rebamipide, partially alleviated the PSL-induced dysbiosis of the gut microbiota. Administering rebamipide with FMT from healthy donors relieved inflammation in mice with Enterococcus faecium-induced colitis.<br><br>CONCLUSION: Colonic mucin controlled the gut microbiota composition, and oral corticosteroid treatment modified the gut microbiota partly by reducing the colonic mucin.}, }
@article {pmid35183993, year = {2022}, author = {Shang, T and Guo, Y and Li, XR and Zhou, Z and Qi, Y and Salahdiin, K and Shen, R and He, S and Wang, M and Shi, ZX and Zhao, X and Yang, J and Fan, G and Wang, Y and Gao, X and Zhu, Y and Feng, Y}, title = {The combination of four main components in Xuebijing injection improved the preventive effects of Cyclosporin A in acute graft-versus-host disease mice by protecting intestinal microenvironment.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {148}, number = {}, pages = {112675}, doi = {10.1016/j.biopha.2022.112675}, pmid = {35183993}, issn = {1950-6007}, mesh = {Acute Disease ; Animals ; Cyclosporine/pharmacology ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Graft vs Host Disease/prevention &amp; control ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Mice ; }, abstract = {Acute graft-versus-host disease (aGVHD) is a major life-threatening complication after Allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT). Although a series of immunosuppressant agents are routinely used as the first-line prevention, the morbidity and mortality rate remains high in allo-HSCT recipients. Our previous work indicated that combining Xuebijing (XBJ) with Cyclosporin A (CSA) is superior to CSA alone in preventing aGVHD. However, it was not clear which compounds in XBJ may prevent aGVHD. Whether the effective compounds in XBJ can be safely combined with CSA to prevent GVHD remain to be evaluated. Here, we accessed whether the combination of four main components in XBJ (C0127) had the same efficacy as XBJ in preventing aGVHD. In addition, the effectiveness of a novel combination therapy (C0127 + CSA) on aGVHD prophylaxis was evaluated using 16 s rRNA sequencing and RNA sequencing approaches in vitro and in vivo. In aGVHD mice, C0127 enhanced the preventive effects of CSA including decreasing mortality, maintaining weight, reducing GVHD score and reducing the expression of IL-6 and TNF-α in serum. Fatal GVHD is a frequent consequence of intestinal tract damage. We found combining C0127 with CSA alleviated the gut damage and maintained the normal physiological function of intestine by H&amp;E staining, intestinal permeability and short chain fatty acid (SCFA) assays. Next, 16 S sequencing analysis of feces showed the combination treatment maintained the intestinal microbial diversity, normalized the intestinal microorganism and prevented flora disorder by reducing the relative abundances of Escherichia coli and Enterococcus. Further, RNA-seq analysis of colonic epithelium revealed C0127 combined with CSA chiefly regulated chemokines and cytokines in IL-17 signaling pathway. The combination treatment reduced the expression of G-CSF and its effector STAT3 (an axis that aggravated gut inflammation and flora disorder) in gut epithelium on mRNA and protein level. These findings indicated that C0127 improved the prevention of CSA in aGVHD mice partially by protecting the gut from damage through normalizing G-CSF signaling, which regulates the intestinal microbiota and the integrity of the epithelial barrier.}, }
@article {pmid35180124, year = {2022}, author = {Hang, Z and Cai, S and Lei, T and Zhang, X and Xiao, Z and Wang, D and Li, Y and Bi, W and Yang, Y and Deng, S and Wang, L and Li, Q and Du, H}, title = {Transfer of Tumor-Bearing Mice Intestinal Flora Can Ameliorate Cognition in Alzheimer's Disease Mice.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {86}, number = {3}, pages = {1287-1300}, doi = {10.3233/JAD-215495}, pmid = {35180124}, issn = {1875-8908}, mesh = {*Alzheimer Disease/therapy ; Animals ; Cognition ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; *Neoplasms ; }, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) is a potential treatment approach for many diseases. Alzheimer's disease (AD) and cancer have been proven to have a specific antagonistic relationship to FMT.<br><br>OBJECTIVE: This article aims to explore whether intestinal flora transplantation from cancer individuals can ameliorate cognitive impairment.<br><br>METHODS: Morris water maze and object recognition tests were performed to assess cognitive function after the fecal flora from tumor-bearing and WT mice were transplanted into AD mice by gavage. The effect of flora transplantation on AD was analyzed by thioflavin T staining, western blot, and 16S RNA sequencing.<br><br>RESULTS: AD mice with FMT significantly improved short-term memory level and cognitive ability compared with Tg&#x200a;+&#x200a;NaCl group. Inflammatory factors in the plasma were regulated, and A&#x3b2; plaques burden in the hippocampus and cortex were decreased. FMT in the tumor-bearing group showed a higher significant amelioration in symptoms compared to the healthy group. 16S RNA sequencing revealed that FMT treatments could reverse the increased Firmicutes and Prevotella and the decreased Bacteroidetes, Bacteroides, and Sutterella in AD mice. AD mice transplanted with tumor-bearing mice feces additionally increased the density of Oscillospira, Odoribacter, and AF12. Furthermore, the predicted functional analyses showed that the metabolism of inorganic and organic salts in the intestinal flora of AD mice was also reversed by FMT.<br><br>CONCLUSION: Intestinal flora transplantation from tumor-bearing mice can ameliorate the cognitive impairment of AD mice.}, }
@article {pmid35179760, year = {2022}, author = {Martinelli, V and Albanese, M and Altieri, M and Annovazzi, P and Arabi, S and Bucello, S and Caleri, F and Cerqua, R and Costanzi, C and Cottone, S and Dalla Costa, G and Direnzo, V and Fantozzi, R and Favaretto, A and Lorefice, L and Montini, F and Noce, A and Plewnia, K and Repice, AM and Sacco, R and Vecchio, D}, title = {Gut-oriented interventions in patients with multiple sclerosis: fact or fiction?.}, journal = {European review for medical and pharmacological sciences}, volume = {26}, number = {3}, pages = {935-946}, doi = {10.26355/eurrev_202202_28003}, pmid = {35179760}, issn = {2284-0729}, mesh = {Animals ; Bile Acids and Salts ; Central Nervous System ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Multiple Sclerosis ; }, abstract = {OBJECTIVE: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS.<br><br>PATIENTS AND METHODS: We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing).<br><br>RESULTS: There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS.<br><br>CONCLUSIONS: Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.}, }
@article {pmid35176320, year = {2022}, author = {Fang, S and Wang, T and Li, Y and Xue, H and Zou, J and Cai, J and Shi, R and Wu, J and Ma, Y}, title = {Gardenia jasminoides Ellis polysaccharide ameliorates cholestatic liver injury by alleviating gut microbiota dysbiosis and inhibiting the TLR4/NF-κB signaling pathway.}, journal = {International journal of biological macromolecules}, volume = {205}, number = {}, pages = {23-36}, doi = {10.1016/j.ijbiomac.2022.02.056}, pmid = {35176320}, issn = {1879-0003}, mesh = {Animals ; Dysbiosis/drug therapy ; *Gardenia ; *Gastrointestinal Microbiome ; Liver ; Mice ; Mice, Inbred C57BL ; NF-kappa B/genetics ; Polysaccharides/pharmacology/therapeutic use ; Signal Transduction ; Toll-Like Receptor 4/genetics ; }, abstract = {Gardenia jasminoides Ellis is a well-known herbal medicine. In this study, the effect of G. jasminoides Ellis polysaccharide (GPS) on liver injury in an alpha-naphthylisothiocyanate (ANIT)-induced cholestatic mouse model and the associated molecular mechanisms were investigated. GPS administration dose-dependently ameliorated impaired hepatic function, including a 2-7-fold decrease in aminotransferase levels, ameliorating tissue damage, upregulating the expression of farnesoid X receptor (FXR) and pregnane X receptor (PXR) and their downstream efflux transporters, and decreasing the levels of 12 bile acids (BAs), in cholestatic mice. Furthermore, GPS ameliorated gut microbiota dysbiosis, improved intestinal barrier function, and reduced serum and hepatic lipopolysaccharide levels 1.5-fold. GPS also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling, decreased the expression of inflammatory factor genes, and ameliorated hepatic inflammation. Notably, fecal microbiota transplantation from GPS-fed mice also increased the hepatic expression of FXR, PXR, and efflux transporters; decreased the levels of 12 BAs; restored intestinal barrier function; and decreased hepatic inflammation mediated by the TLR4/NF-κB pathway. In conclusion, GPS has a protective effect against cholestatic liver injury through modulation of gut microbiota and inhibition of the TLR4/NF-κB pathway. Regulating gut microbiota using herbal medicine polysaccharides may hold unique therapeutic promise for cholestatic liver diseases.}, }
@article {pmid35176247, year = {2022}, author = {Mayneris-Perxachs, J and Castells-Nobau, A and Arnoriaga-Rodríguez, M and Garre-Olmo, J and Puig, J and Ramos, R and Martínez-Hernández, F and Burokas, A and Coll, C and Moreno-Navarrete, JM and Zapata-Tona, C and Pedraza, S and Pérez-Brocal, V and Ramió-Torrentà, L and Ricart, W and Moya, A and Martínez-García, M and Maldonado, R and Fernández-Real, JM}, title = {Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {3}, pages = {340-356.e8}, doi = {10.1016/j.chom.2022.01.013}, pmid = {35176247}, issn = {1934-6069}, mesh = {Animals ; *Bacteriophages/genetics ; *Caudovirales ; *Diptera ; Executive Function ; *Gastrointestinal Microbiome/genetics ; Humans ; Mice ; }, abstract = {Growing evidence implicates the gut microbiome in cognition. Viruses, the most abundant life entities on the planet, are a commonly overlooked component of the gut virome, dominated by the Caudovirales and Microviridae bacteriophages. Here, we show in a discovery (n = 114) and a validation cohort (n = 942) that subjects with increased Caudovirales and Siphoviridae levels in the gut microbiome had better performance in executive processes and verbal memory. Conversely, increased Microviridae levels were linked to a greater impairment in executive abilities. Microbiota transplantation from human donors with increased specific Caudovirales (>90% from the Siphoviridae family) levels led to increased scores in the novel object recognition test in mice and up-regulated memory-promoting immediate early genes in the prefrontal cortex. Supplementation of the Drosophila diet with the 936 group of lactococcal Siphoviridae bacteriophages resulted in increased memory scores and upregulation of memory-involved brain genes. Thus, bacteriophages warrant consideration as novel actors in the microbiome-brain axis.}, }
@article {pmid35172356, year = {2022}, author = {Carlson, TJ and Gonzales-Luna, AJ and Garey, KW}, title = {Fulminant Clostridioides difficile Infection: A Review of Treatment Options for a Life-Threatening Infection.}, journal = {Seminars in respiratory and critical care medicine}, volume = {43}, number = {1}, pages = {28-38}, doi = {10.1055/s-0041-1740973}, pmid = {35172356}, issn = {1098-9048}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/drug therapy/therapy ; Critical Illness/therapy ; Fecal Microbiota Transplantation ; Humans ; Vancomycin/therapeutic use ; }, abstract = {Fulminant Clostridioides difficile infection (FCDI) encompasses 3 to 5% of all CDI cases with associated mortality rates between 30 and 40%. Major treatment modalities include surgery and medical management with antibiotic and nonantibiotic therapies. However, identification of patients with CDI that will progress to FCDI is difficult and makes it challenging to direct medical management and identify those who may benefit from surgery. Furthermore, since it is difficult to study such a critically ill population, data investigating treatment options are limited. Surgical management with diverting loop ileostomy (LI) instead of a total abdominal colectomy (TAC) with end ileostomy has several appealing advantages, and studies have not consistently demonstrated a clinical benefit with this less-invasive strategy, so both LI and TAC remain acceptable surgical options. Successful medical management of FCDI is complicated by pharmacokinetic changes that occur in critically ill patients, and there is an absence of high-quality studies that included patients with FCDI. Recommendations accordingly include a combination of antibiotics administered via multiple routes to ensure adequate drug concentrations in the colon: intravenous metronidazole, high-dose oral vancomycin, and rectal vancomycin. Although fidaxomicin is now recommended as first-line therapy for non-FCDI, there are limited clinical data to support its use in FCDI. Several nonantibiotic therapies, including fecal microbiota transplantation and intravenous immunoglobulin, have shown success as adjunctive therapies, but they are unlikely to be effective alone. In this review, we aim to summarize diagnosis and treatment options for FCDI.}, }
@article {pmid35168592, year = {2022}, author = {Knudsen, MD and Kvaerner, AS and Botteri, E and Holme, &#xd8; and Hjartåker, A and Song, M and Thiis-Evensen, E and Randel, KR and Hoff, G and Berstad, P}, title = {Lifestyle predictors for inconsistent participation to fecal based colorectal cancer screening.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {172}, pmid = {35168592}, issn = {1471-2407}, support = {2019070//Helse S&#xf8;r-&#xd8;st RHF/ ; }, mesh = {Adult ; Alcohol Drinking/psychology ; Body Mass Index ; Colorectal Neoplasms/*prevention &amp; control ; Diet/psychology/statistics &amp; numerical data ; Early Detection of Cancer/psychology/*statistics &amp; numerical data ; Exercise/psychology/statistics &amp; numerical data ; Female ; Healthy Lifestyle ; Humans ; *Life Style ; Logistic Models ; Male ; Occult Blood ; Odds Ratio ; Patient Acceptance of Health Care/*statistics &amp; numerical data ; Program Evaluation ; Risk Factors ; Smoking/psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Consistent participation in colorectal cancer (CRC) screening with repeated fecal immunochemical test (FIT) is important for the success of the screening program. We investigated whether lifestyle risk factors for CRC were related to inconsistent participation in up to four rounds of FIT-screening.<br><br>METHOD: We included data from 3,051 individuals who participated in up to four FIT-screening rounds and returned a lifestyle questionnaire. Using logistic regression analyses, we estimated associations between smoking habits, body mass index (BMI), physical activity, alcohol consumption, diet and a healthy lifestyle score (from least favorable 0 to most favorable 5), and inconsistent participation (i.e. not participating in all rounds of eligible FIT screening invitations).<br><br>RESULTS: Altogether 721 (24%) individuals were categorized as inconsistent participants Current smoking and BMI &#x2265;30&#x2009;kg/m[2] were associated with inconsistent participation; odds ratios (ORs) and 95% confidence intervals (CIs) were 1.54 (1.21-2.95) and 1.54 (1.20-1.97), respectively. A significant trend towards inconsistent participation by a lower healthy lifestyle score was observed (p <&#x2009;0.05).<br><br>CONCLUSIONS: Lifestyle behaviors were associated with inconsistent participation in FIT-screening. Initiatives aimed at increasing participation rates among those with the unhealthiest lifestyle have a potential to improve the efficiency of screening.}, }
@article {pmid35166723, year = {2022}, author = {Pettinelli, P and Arendt, BM and Schwenger, KJP and Sivaraj, S and Bhat, M and Comelli, EM and Lou, W and Allard, JP}, title = {Relationship Between Hepatic Gene Expression, Intestinal Microbiota, and Inferred Functional Metagenomic Analysis in NAFLD.}, journal = {Clinical and translational gastroenterology}, volume = {13}, number = {7}, pages = {e00466}, pmid = {35166723}, issn = {2155-384X}, support = {NMD-86922//CIHR/Canada ; MOP-89705//CIHR/Canada ; }, mesh = {Bacteria/genetics ; *Gastrointestinal Microbiome/genetics ; Gene Expression ; Humans ; *Insulin Resistance ; *Non-alcoholic Fatty Liver Disease/complications ; }, abstract = {INTRODUCTION: We previously reported a lower fecal abundance of Ruminococcus spp., Faecalibacterium prausnitzii , and Coprococcus spp. in nonalcoholic fatty liver disease (NAFLD). In this article, we assess the associations between hepatic gene expression, the specific taxa, and bacterial pathways.<br><br>METHODS: The relationships between hepatic genes that were differentially expressed in patients with NAFLD vs healthy controls (HC) and the abundance of these specific taxa were studied. Inferred functional metagenomic analysis using Piphillin was also performed to investigate associations with bacterial pathways.<br><br>RESULTS: Fifteen patients with NAFLD and 6 HC participated. Of 728 hepatic genes examined, 176 correlated with the abundance of Ruminococcus spp., 138 with F. prausnitzii , and 92 with Coprococcus spp. For Ruminococcus spp., genes were enriched in gene ontology (GO) terms related to apoptotic process, response to external and cytokine stimuli, and regulation of signaling. Several genes related to the Kyoto Encyclopedia of Genes and Genomes pathway insulin resistance were correlated with F. prausnitzii . The hepatic genes associated with F. prausnitzii were enriched in GO terms related to cellular response to different stimuli, apoptotic process, and regulation of metabolic pathways. For Coprococcus spp., only the GO term response to external stimulus was enriched. There was a distinct pattern of associations between hepatic genes and bacterial taxa in NAFLD vs HC. For bacterial pathways, 65 and 18 hepatic genes correlated with bacterial metabolic functions in NAFLD and HC, respectively.<br><br>DISCUSSION: Hepatic gene expression related to insulin resistance, inflammation, external stimuli, and apoptosis correlated with bacterial taxa. Patients with NAFLD showed a higher presence of bacterial pathways associated with lipid metabolism.}, }
@article {pmid35166124, year = {2022}, author = {Ben Fradj, S and Nédélec, E and Salvi, J and Fouesnard, M and Huillet, M and Pallot, G and Cansell, C and Sanchez, C and Philippe, C and Gigot, V and Lemoine, A and Trompier, D and Henry, T and Petrilli, V and Py, BF and Guillou, H and Loiseau, N and Ellero-Simatos, S and Nahon, JL and Rovère, C and Grober, J and Boudry, G and Douard, V and Benani, A}, title = {Evidence for Constitutive Microbiota-Dependent Short-Term Control of Food Intake in Mice: Is There a Link with Inflammation, Oxidative Stress, Endotoxemia, and GLP-1?.}, journal = {Antioxidants &amp; redox signaling}, volume = {37}, number = {4-6}, pages = {349-369}, doi = {10.1089/ars.2021.0095}, pmid = {35166124}, issn = {1557-7716}, mesh = {Animals ; *Appetite Depressants ; Eating ; *Endotoxemia ; Glucagon-Like Peptide 1 ; Inflammation ; Mice ; Mice, Inbred NOD ; *Microbiota ; Oxidative Stress ; }, abstract = {Aims: Although prebiotics, probiotics, and fecal transplantation can alter the sensation of hunger and/or feeding behavior, the role of the constitutive gut microbiota in the short-term regulation of food intake during normal physiology is still unclear. Results: An antibiotic-induced microbiota depletion study was designed to compare feeding behavior in conventional and microbiota-depleted mice. Tissues were sampled to characterize the time profile of microbiota-derived signals in mice during consumption of either standard or high-fat food for 1 h. Pharmacological and genetic tools were used to evaluate the contribution of postprandial endotoxemia and inflammatory responses in the short-term regulation of food intake. We observed constitutive microbial and macronutrient-dependent control of food intake at the time scale of a meal; that is, within 1 h of food introduction. Specifically, microbiota depletion increased food intake, and the microbiota-derived anorectic effect became significant during the consumption of high-fat but not standard food. This anorectic effect correlated with a specific postprandial microbial metabolic signature, and did not require postprandial endotoxemia or an NOD-, LRR-, and Pyrin domain-containing protein 3-inflammasome-mediated inflammatory response. Innovation and Conclusion: These findings show that the gut microbiota controls host appetite at the time scale of a meal under normal physiology. Interestingly, a microbiota-derived anorectic effect develops specifically with a high-fat meal, indicating that gut microbiota activity is involved in the satietogenic properties of foods. Antioxid. Redox Signal. 37, 349-369.}, }
@article {pmid35165993, year = {2022}, author = {Parker, G and Spoelma, MJ and Rhodes, N}, title = {Faecal microbiota transplantation for bipolar disorder: A detailed case study.}, journal = {Bipolar disorders}, volume = {24}, number = {5}, pages = {559-563}, pmid = {35165993}, issn = {1399-5618}, mesh = {*Bipolar Disorder/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid35163286, year = {2022}, author = {Alharthi, A and Alhazmi, S and Alburae, N and Bahieldin, A}, title = {The Human Gut Microbiome as a Potential Factor in Autism Spectrum Disorder.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35163286}, issn = {1422-0067}, mesh = {Autism Spectrum Disorder/*microbiology ; Brain/metabolism ; Brain-Gut Axis/*physiology ; Dietary Supplements ; Dysbiosis/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Microbiota ; Prebiotics ; Probiotics ; }, abstract = {The high prevalence of gastrointestinal (GI) disorders among autism spectrum disorder (ASD) patients has prompted scientists to look into the gut microbiota as a putative trigger in ASD pathogenesis. Thus, many studies have linked the gut microbial dysbiosis that is frequently observed in ASD patients with the modulation of brain function and social behavior, but little is known about this connection and its contribution to the etiology of ASD. This present review highlights the potential role of the microbiota-gut-brain axis in autism. In particular, it focuses on how gut microbiota dysbiosis may impact gut permeability, immune function, and the microbial metabolites in autistic people. We further discuss recent findings supporting the possible role of the gut microbiome in initiating epigenetic modifications and consider the potential role of this pathway in influencing the severity of ASD. Lastly, we summarize recent updates in microbiota-targeted therapies such as probiotics, prebiotics, dietary supplements, fecal microbiota transplantation, and microbiota transfer therapy. The findings of this paper reveal new insights into possible therapeutic interventions that may be used to reduce and cure ASD-related symptoms. However, well-designed research studies using large sample sizes are still required in this area of study.}, }
@article {pmid35159245, year = {2022}, author = {Cold, F and Svensson, CK and Petersen, AM and Hansen, LH and Helms, M}, title = {Long-Term Safety Following Faecal Microbiota Transplantation as a Treatment for Recurrent Clostridioides difficile Infection Compared with Patients Treated with a Fixed Bacterial Mixture: Results from a Retrospective Cohort Study.}, journal = {Cells}, volume = {11}, number = {3}, pages = {}, pmid = {35159245}, issn = {2073-4409}, support = {7076-00129B//Danish Innovation Fund/ ; }, mesh = {*Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces/microbiology ; Humans ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) is the recommended treatment for recurrent C. difficile infection (rCDI) following a second recurrence. FMT is considered safe in the short term when procedures for the screening of donors and transferred material are followed. However, the long-term safety profile of FMT treatment is largely unknown. In a retrospective cohort study, we assessed the long-term safety of patients treated for rCDI with FMT or a fixed bacterial mixture, rectal bacteriotherapy (RBT). The overall survival, risk of hospital admission, onset of certain pre-specified diseases (cancer, diabetes mellitus, hypertension and inflammatory bowel disease) and risk of being diagnosed with a multidrug-resistant organism were assessed by undertaking a review of the treated patients' medical records for up to five years following treatment. A total of 280 patients were treated for rCDI with FMT (n = 145) or RBT (n = 135) between 2016 and 2020. In the five years following treatment, there were no differences in survival (adjusted hazard ratio (aHR) 1.03; 95% CI 0.68-1.56), p = 0.89), risk of hospital admission ((aHR 0.92; 95% CI 0.72-1.18), p = 0.5) or onset of any of the analysed diseases. In conclusion, FMT was not associated with increased mortality, risk of hospital admission or onset of disease following treatment when compared with RBT.}, }
@article {pmid35158960, year = {2022}, author = {Bou Zerdan, M and Niforatos, S and Nasr, S and Nasr, D and Ombada, M and John, S and Dutta, D and Lim, SH}, title = {Fecal Microbiota Transplant for Hematologic and Oncologic Diseases: Principle and Practice.}, journal = {Cancers}, volume = {14}, number = {3}, pages = {}, pmid = {35158960}, issn = {2072-6694}, abstract = {Understanding of the importance of the normal intestinal microbial community in regulating microbial homeostasis, host metabolism, adaptive immune responses, and gut barrier functions has opened up the possibility of manipulating the microbial composition to modulate the activity of various intestinal and systemic diseases using fecal microbiota transplant (FMT). It is therefore not surprising that use of FMT, especially for treating relapsed/refractory Clostridioides difficile infections (CDI), has increased over the last decade. Due to the complexity associated with and treatment for these diseases, patients with hematologic and oncologic diseases are particularly susceptible to complications related to altered intestinal microbial composition. Therefore, they are an ideal population for exploring FMT as a therapeutic approach. However, there are inherent factors presenting as obstacles for the use of FMT in these patients. In this review paper, we discussed the principles and biologic effects of FMT, examined the factors rendering patients with hematologic and oncologic conditions to increased risks for relapsed/refractory CDI, explored ongoing FMT studies, and proposed novel uses for FMT in these groups of patients. Finally, we also addressed the challenges of applying FMT to these groups of patients and proposed ways to overcome these challenges.}, }
@article {pmid35158238, year = {2022}, author = {Zhou, Y and Feng, Y and Cen, R and Hou, X and Yu, H and Sun, J and Zhou, L and Ji, Q and Zhao, L and Wang, Y and Li, Q}, title = {San-Wu-Huang-Qin decoction attenuates tumorigenesis and mucosal barrier impairment in the AOM/DSS model by targeting gut microbiome.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {98}, number = {}, pages = {153966}, doi = {10.1016/j.phymed.2022.153966}, pmid = {35158238}, issn = {1618-095X}, abstract = {BACKGROUND: A classic herbal formula San-Wu-Huang-Qin (SWHQ) decoction has been widely used in clinical practices to prevent and treat colorectal cancer (CRC) for years, but its anti-tumorigenic properties and the underlying mechanisms remain undetermined.<br><br>PURPOSE: The present study used a CRC mouse model to clarify whether and how SWHQ suppresses tumorigenesis.<br><br>METHODS: Different doses of SWHQ were gavaged to the AOM/DSS model mice to examine its anti-tumor efficacy in comparison with the positive control drug Aspirin. The underlying microbiota-driven anti-tumor action of SWHQ was proven with bacterial manipulations by fecal microbial transplantation (FMT) in vivo and anaerobic culturing in vitro.<br><br>RESULTS: SWHQ decoction dose-dependently reduced colonic tumor numbers/loads of AOM/DSS models and suppressed their disease activity index scores. SWHQ also recovered epithelial MUC2 secretion and colonic tight junction protein (ZO-1 and claudin1) expression in the mouse model. Such inhibitory impact on tumorigenesis and mucosal barrier impairment was found to be associated with modulation of gut dysbiosis, particularly for suppressing lipopolysaccharide (LPS) producers. The FMT experiment confirmed the substantial contribution of SWHQ-reshaped microbiota to anti-tumor function and mucosal barrier protection. Moreover, LPS-activated TLR4/NF-&#x3ba;B signaling and its downstream pro-inflammatory factors were significantly suppressed in the colon of SWHQ-treated models and SWHQ-reshaped microbiota recipients.<br><br>CONCLUSIONS: We demonstrated that the SWHQ effectively inhibited tumorigenesis and protect mucosal barrier in CRC at least partially by targeting gut microbiota. This study provides scientific basis for the clinical usage of SWHQ in CRC intervention and prevention.}, }
@article {pmid35156893, year = {2022}, author = {Mazzawi, T and Hausken, T and El-Salhy, M}, title = {Changes in colonic enteroendocrine cells of patients with irritable bowel syndrome following fecal microbiota transplantation.}, journal = {Scandinavian journal of gastroenterology}, volume = {57}, number = {7}, pages = {792-796}, doi = {10.1080/00365521.2022.2036809}, pmid = {35156893}, issn = {1502-7708}, mesh = {Adult ; Aged ; Double-Blind Method ; Enteroendocrine Cells ; Fecal Microbiota Transplantation/methods ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; Male ; Middle Aged ; Treatment Outcome ; }, abstract = {OBJECTIVES: The aim was to investigate the effect of fecal microbiota transplantation (FMT) on colonic enteroendocrine cells densities in patients with irritable bowel syndrome (IBS).<br><br>MATERIALS AND METHODS: This study is connected to the REFIT study, a double-blinded placebo-controlled trial to investigate using FMT for IBS treatment. Eighty-three subjects received either donor-FMT or placebo FMT (own feces) by colonoscope to cecum. Biopsies were obtained from sigmoid colon. Ten responders and ten non-responders consented to new biopsy one-year after FMT. Sixteen patients received donor-FMT and four received placebo FMT. Biopsies were immunostained for all of the colonic enteroendocrine cells and were quantified using computerized image analysis.Allocation sequence was revealed after obtaining re-biopsies and cells quantification.<br><br>RESULTS: Scores for IBS-SSS (mean&#x2009;&#xb1;&#x2009;SEM) of responders (eight of 10 patients who received donor FMT) and non-responders changed from baseline to one year after FMT (297&#x2009;&#xb1;&#x2009;11 and 81&#x2009;&#xb1;&#x2009;16, p&#x2009;<&#x2009;.0001, and 270&#x2009;&#xb1;&#x2009;17 and 291&#x2009;&#xb1;&#x2009;16, p&#x2009;=&#x2009;.15, respectively). Using paired t-test to compare enteroendocrine cells densities one-year after FMT to baseline showed significant increase only in somatostatin immunoreactive cells density in the total IBS responders group (p&#x2009;=&#x2009;.023) and who received donor-FMT (p&#x2009;=&#x2009;.038). The densities of peptide YY and enteroglucagon immunoreactive cells increased significantly (p = .04 and .035, respectively) in donor-FMT recipients. No significant changes were noted in placebo FMT or nonresponders subgroups.<br><br>CONCLUSION: This study shows that colonic enteroendocrine cells densities significantly change in responders group that received donor-FMT. The mechanisms for the cross talks between gut microbiota and colonic enteroendocrine cells remain to be investigated.}, }
@article {pmid35156318, year = {2022}, author = {Liu, B and Chen, X and Zhou, L and Li, J and Wang, D and Yang, W and Wu, H and Yao, J and Yang, G and Wang, C and Feng, J and Jiang, T}, title = {The gut microbiota of bats confers tolerance to influenza virus (H1N1) infection in mice.}, journal = {Transboundary and emerging diseases}, volume = {69}, number = {5}, pages = {e1469-e1487}, doi = {10.1111/tbed.14478}, pmid = {35156318}, issn = {1865-1682}, support = {31922050//National Natural Science Foundation of China/ ; 32071492//National Natural Science Foundation of China/ ; 32171489//National Natural Science Foundation of China/ ; 20200201186JC//The Jilin Province Science and Technology Development Project/ ; }, mesh = {Animals ; Anti-Bacterial Agents ; Antiviral Agents ; *Chiroptera ; Flavonoids ; *Gastrointestinal Microbiome ; *Influenza A Virus, H1N1 Subtype ; *Isoflavones ; Mice ; *Virus Diseases/veterinary ; }, abstract = {Pathogens from wild animals cause approximately 60% of emerging infectious diseases (EIDs). Studies on the immune systems of natural hosts are helpful for preventing the spread of EIDs. Bats are natural hosts for many emerging infectious pathogens and have a unique immune system that often coexists with pathogens without infection. Previous studies have shown that some genes and proteins may help bats fight virus infection, but little is known about the function of the bat gut microbiome on immunity. Here, we transplanted gut microbiota from wild bats (Great Himalayan Leaf-nosed bats, Hipposideros armiger) into antibiotic-treated mice, and found that the gut microbiota from bats regulated the immune system faster than mice after antibiotic treatment. Moreover, we infected mice with H1N1, and found that the gut microbiota of bats could effectively protect mice, leading to decreased inflammatory response and increased survival rate. Finally, metabolomics analysis showed that the gut microbiota of bats produced more flavonoid and isoflavones. Our results demonstrate that the quick-start innate immune response endowed by bat gut microbiota and the regulatory and antiviral effects of gut microbiota metabolites successfully ensured mouse survival after viral challenge. To our knowledge, our study was the first to use fecal microbiota transplantation (FMT) to transplant the gut microbiota of bats into mice, and the first to provide evidence that the gut microbiota of bats confers tolerance to viral infections.}, }
@article {pmid35155283, year = {2022}, author = {Zhou, A and Yuan, Y and Yang, M and Huang, Y and Li, X and Li, S and Yang, S and Tang, B}, title = {Crosstalk Between the Gut Microbiota and Epithelial Cells Under Physiological and Infectious Conditions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {832672}, pmid = {35155283}, issn = {2235-2988}, mesh = {*COVID-19 ; *Clostridioides difficile ; Epithelial Cells ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa ; SARS-CoV-2 ; }, abstract = {The gastrointestinal tract (GIT) is considered the largest immunological organ, with a diverse gut microbiota, that contributes to combatting pathogens and maintaining human health. Under physiological conditions, the crosstalk between gut microbiota and intestinal epithelial cells (IECs) plays a crucial role in GIT homeostasis. Gut microbiota and derived metabolites can compromise gut barrier integrity by activating some signaling pathways in IECs. Conversely, IECs can separate the gut microbiota from the host immune cells to avoid an excessive immune response and regulate the composition of the gut microbiota by providing an alternative energy source and releasing some molecules, such as hormones and mucus. Infections by various pathogens, such as bacteria, viruses, and parasites, can disturb the diversity of the gut microbiota and influence the structure and metabolism of IECs. However, the interaction between gut microbiota and IECs during infection is still not clear. In this review, we will focus on the existing evidence to elucidate the crosstalk between gut microbiota and IECs during infection and discuss some potential therapeutic methods, including probiotics, fecal microbiota transplantation (FMT), and dietary fiber. Understanding the role of crosstalk during infection may help us to establish novel strategies for prevention and treatment in patients with infectious diseases, such as C. difficile infection, HIV, and COVID-19.}, }
@article {pmid35151859, year = {2022}, author = {Xu, X and Zhan, G and Chen, R and Wang, D and Guan, S and Xu, H}, title = {Gut microbiota and its role in stress-induced hyperalgesia: Gender-specific responses linked to different changes in serum metabolites.}, journal = {Pharmacological research}, volume = {177}, number = {}, pages = {106129}, doi = {10.1016/j.phrs.2022.106129}, pmid = {35151859}, issn = {1096-1186}, mesh = {Animals ; Fecal Microbiota Transplantation ; Feces ; Female ; *Gastrointestinal Microbiome/physiology ; Hyperalgesia ; Male ; Mice ; Pain ; }, abstract = {Long-term stress causes hyperalgesia; and there are gender differences in the mechanism of pain in male and female individuals. The role of gut microbiota in pain has also been verified. However, whether gut microbiota plays a role in hyperalgesia caused by chronic restraint stress (CRS) with gender differences has not been explored. This study investigated the role of gut microbiota in CRS-induced hyperalgesia gender-specifically through 16 S ribosomal RNA (16 S rRNA) gene sequencing and untargeted metabolomic analysis using liquid chromatography-mass spectrometry (LC-MS). The study found that both male and female mice experienced hyperalgesia after CRS and antibiotic treatment. 16 S rRNA gene sequencing reveals gender differences in the fecal microbiota induced by CRS. The pain threshold decreased after transplanting the fecal microbiota from the male and female CRS group to the corresponding pseudo-germ-free mice. In addition, this study detected gender differences in the host gut microbiota and serum metabolism induced by fecal microbiota transplantation (FMT). Specifically, the different serum metabolites between the pseudo-germ-free mice receiving FMT from the CRS group and those from the control group were mainly involved in bile secretion and steroid hormone biosynthesis for male mice, and in taurine and hypotaurine metabolism and tryptophan metabolism for female mice. In summary, the gut microbiota participates in stress-induced hyperalgesia (SIH) with gender differences by influencing the host's gut microbiota composition and serum metabolism. Therefore, our findings provided insights into developing novel gut microbiota-associated drugs for the management of gender-specific SIH.}, }
@article {pmid35151796, year = {2022}, author = {Chang, L and Wei, Y and Hashimoto, K}, title = {Brain-gut-microbiota axis in depression: A historical overview and future directions.}, journal = {Brain research bulletin}, volume = {182}, number = {}, pages = {44-56}, doi = {10.1016/j.brainresbull.2022.02.004}, pmid = {35151796}, issn = {1873-2747}, mesh = {Brain ; Brain-Gut Axis ; Depression ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Depression is the most common mental disorder and a leading cause of disability worldwide. Despite abundant research, the precise mechanisms underlying the pathophysiology of depression remain elusive. Accumulating evidence from preclinical and clinical studies suggests that alterations in the gut microbiota, microbe-derived short-chain fatty acids, D-amino acids and metabolites play a key role in the pathophysiology of depression via the brain-gut-microbiota axis, including the neural and immune systems. Notably, the brain-gut-microbiota axis might play a crucial role in susceptibility versus resilience in rodents exposed to stress. Vagotomy is reported to block depression-like phenotypes in rodents after fecal microbiota transplantation of "depression-related" microbiome, suggesting that the vagus nerve influences depression through the brain-gut-microbiota axis. In this article, we review recent findings regarding the brain-gut-microbiota axis in depression and discuss its potential as a therapeutic target for depression.}, }
@article {pmid35151729, year = {2022}, author = {Hu, C and Sun, B and Liu, M and Yu, J and Zhou, X and Chen, L}, title = {Fecal transplantation from young zebrafish donors efficiently ameliorates the lipid metabolism disorder of aged recipients exposed to perfluorobutanesulfonate.}, journal = {The Science of the total environment}, volume = {823}, number = {}, pages = {153758}, doi = {10.1016/j.scitotenv.2022.153758}, pmid = {35151729}, issn = {1879-1026}, mesh = {Animals ; Fecal Microbiota Transplantation ; Female ; Fluorocarbons ; Lipid Metabolism ; *Lipid Metabolism Disorders ; *Probiotics/pharmacology ; Sulfonic Acids ; Zebrafish ; }, abstract = {Aging is a biological process that is accompanied by the gradual loss of physiological functions. Under the context of ubiquitous and persistent environmental pollution, the elderly will be more vulnerable to the detrimental effects of toxic pollutants than the young. With objectives to explore effective measures to ameliorate the double stress of aging and toxicants, the present study transplanted the feces from young zebrafish donors to aged recipients, which were concurrently exposed to perfluorobutanesulfonate (PFBS), an emerging environmental pollutant of international concern. After exposure, growth, hepatic structural organization, and lipid metabolism were examined. The results showed that, irrespective of PFBS toxicity, transplantation of young feces significantly enhanced the growth of the aged. In the livers of aged and PFBS-exposed zebrafish, vacuolization symptom was prevalently observed, while young fecal transplantation alleviated the structural defects in aged livers. In the gut of the elderly, digestive activity of lipids was promoted after the transplantation of young feces. The blood of the aged females accumulated significantly higher concentration of triglyceride (TG) than the young counterparts (2.6-fold), implying that the elderly were at high risk of cardiovascular diseases. PFBS treatment of the aged further increased blood TG levels by 2.0-fold relative to the aged control group, pointing to the aggravation of the health of the elderly by environmental pollution. However, it is intriguing that young fecal transplantation efficiently inhibited the metabolic toxicity of PFBS and restored the normal level of blood TG, which provided more evidence about the benefit of young fecal transplant to improve the health of the aged individuals. In the aged livers transplanted with young feces, mitochondrial β-oxidation of fatty acids was consistently activated. Overall, the present study verified the efficacy of young fecal transplantation to mitigate the metabolic disorders resulting from aging and an environmental pollutant.}, }
@article {pmid35150892, year = {2022}, author = {Portal, TM and Vanmechelen, B and Van Espen, L and Jansen, D and Teixeira, DM and de Sousa, ESA and da Silva, VP and de Lima, JS and Reymão, TKA and Sequeira, CG and da Silva Ventura, AMR and da Silva, LD and Resque, HR and Matthijnssens, J and Gabbay, YB}, title = {Molecular characterization of the gastrointestinal eukaryotic virome in elderly people in Belem, Para, Brazil.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {99}, number = {}, pages = {105241}, doi = {10.1016/j.meegid.2022.105241}, pmid = {35150892}, issn = {1567-7257}, mesh = {Aged ; Animals ; Brazil/epidemiology ; Eukaryota ; Feces ; *Gastroenteritis/epidemiology ; Genotype ; Horses ; Humans ; Phylogeny ; *Rotavirus/genetics ; *Rotavirus Infections ; Virome ; *Viruses ; }, abstract = {Acute gastroenteritis is one of the main causes of mortality and morbidity worldwide, affecting mainly children, the immunocompromised and elderly people. Enteric viruses, especially rotavirus A, are considered important etiological agents, while long-term care facilities are considered favorable environments for the occurrence of sporadic cases and outbreaks of acute gastroenteritis. Therefore, it is important to monitor the viral agents present in nursing homes, especially because studies involving the elderly population in Brazil are scarce, resulting in a lack of available virological data. As a result, the causative agent remains unidentified in a large number of reported acute gastroenteritis cases. However, the advent of next-generation sequencing provides new opportunities for viral detection and discovery. The aim of this study was to identify the viruses that circulate among elderly people with and without acute gastroenteritis, living in residential care homes in Belém, Pará, Brazil, between 2017 and 2019. Ninety-three samples were collected and screened by immunochromatography and qPCR. After, the samples were analyzed individually or in pools by next generation sequencing to identify the viruses circulating in this population. In 26 sequenced samples, members of 13 eukaryotic virus families were identified. The most abundantly present virus families were Parvoviridae, Genomoviridae and Smacoviridae. Contigs displaying similarity to pegiviruses were also detected. Furthermore, a near-complete rotavirus A genome was obtained and could be classified as G3P[8] genotype with the equine DS-1-like genetic background. Complete sequences of the VP4 and VP7 genes of a rotavirus C were also detected, belonging to G4P[2]. This study demonstrates the first characterization of the gastrointestinal virome in elderly in Northern Brazil. A diversity of viruses was found to be present in patients with and without diarrhea, reinforcing the need to monitor elderly people residing in long-term care facilities, especially in cases of acute gastroenteritis.}, }
@article {pmid35146405, year = {2022}, author = {Sharma, VK and Prateeksha,  and Gupta, SC and Singh, BN and Rao, CV and Barik, SK}, title = {Cinnamomum verum-derived bioactives-functionalized gold nanoparticles for prevention of obesity through gut microbiota reshaping.}, journal = {Materials today. Bio}, volume = {13}, number = {}, pages = {100204}, pmid = {35146405}, issn = {2590-0064}, abstract = {Existing drugs have limited success in managing obesity in human due to their low efficacy and severe side-effects. Surface-modified gold nanoparticles have now received considerable attention of researchers for efficient biomedical applications owing to their superior uptake by cells, biocompatibility, hydrophilicity and non-immunogenicity. Here we prepared Cinnamomum verum derived bioactives-functionalized gold nanoparticles (Au@P-NPs) and assessed their impact on obesity and related immune-metabolic complications in high-fat diet (HFD)-induced obese mice using metabolic experiments along with 16S RNA gene-based gut microbial profiling and faecal microbiota transplantation (FMT). Au@P-NPs treatment prevented weight gain, decreased fat deposition, reduced metabolic inflammation and endotoxaemia in HFD-fed mice. Au@P-NPs-treated group exhibited better glucose tolerance and insulin sensitivity than HFD-fed control mice, and got completely protected against hepatic steatosis. These impacts were related to increased energy expenditure and enhanced Ucp1 expression in the brown adipose tissues of Au@P-NPs-administered animals, which strongly linked with the mRNA expression of the membrane bile acid receptor TGR5. Treatment of HFD-fed animals with Au@P-NPs altered plasma bile acid profile, and increased Akkermansia muciniphila and decreased Lactobacillus populations in the faeces. Au@P-NPs-treated animals revealed altered plasma bile acid profile, and increased Akkermansia muciniphila and decreased Lactobacillus populations in the faeces. FMT experiments showed lesser weight gain and greater energy expenditure in the mice fed with faecal suspension from Au@P-NPs-treated animals than that from HFD-fed mice. These results clearly establish that gold nanoparticles functionalized with bioactive compounds of C. verum have high potential to be an anti-obesity drug.}, }
@article {pmid35145413, year = {2022}, author = {Singh, R and Zogg, H and Ghoshal, UC and Ro, S}, title = {Current Treatment Options and Therapeutic Insights for Gastrointestinal Dysmotility and Functional Gastrointestinal Disorders.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {808195}, pmid = {35145413}, issn = {1663-9812}, abstract = {Functional gastrointestinal disorders (FGIDs) have been re-named as disorders of gut-brain interactions. These conditions are not only common in clinical practice, but also in the community. In reference to the Rome IV criteria, the most common FGIDs, include functional dyspepsia (FD) and irritable bowel syndrome (IBS). Additionally, there is substantial overlap of these disorders and other specific gastrointestinal motility disorders, such as gastroparesis. These disorders are heterogeneous and are intertwined with several proposed pathophysiological mechanisms, such as altered gut motility, intestinal barrier dysfunction, gut immune dysfunction, visceral hypersensitivity, altered GI secretion, presence and degree of bile acid malabsorption, microbial dysbiosis, and alterations to the gut-brain axis. The treatment options currently available include lifestyle modifications, dietary and gut microbiota manipulation interventions including fecal microbiota transplantation, prokinetics, antispasmodics, laxatives, and centrally and peripherally acting neuromodulators. However, treatment that targets the pathophysiological mechanisms underlying the symptoms are scanty. Pharmacological agents that are developed based on the cellular and molecular mechanisms underlying pathologies of these disorders might provide the best avenue for future pharmaceutical development. The currently available therapies lack long-term effectiveness and safety for their use to treat motility disorders and FGIDs. Furthermore, the fundamental challenges in treating these disorders should be defined; for instance, 1. Cause and effect cannot be disentangled between symptoms and pathophysiological mechanisms due to current therapies that entail the off-label use of medications to treat symptoms. 2. Despite the knowledge that the microbiota in our gut plays an essential part in maintaining gut health, their exact functions in gut homeostasis are still unclear. What constitutes a healthy microbiome and further, the precise definition of gut microbial dysbiosis is lacking. More comprehensive, large-scale, and longitudinal studies utilizing multi-omics data are needed to dissect the exact contribution of gut microbial alterations in disease pathogenesis. Accordingly, we review the current treatment options, clinical insight on pathophysiology, therapeutic modalities, current challenges, and therapeutic clues for the clinical care and management of functional dyspepsia, gastroparesis, irritable bowel syndrome, functional constipation, and functional diarrhea.}, }
@article {pmid35143877, year = {2022}, author = {Zhang, Y and Fan, Q and Hou, Y and Zhang, X and Yin, Z and Cai, X and Wei, W and Wang, J and He, D and Wang, G and Yuan, Y and Hao, H and Zheng, X}, title = {Bacteroides species differentially modulate depression-like behavior via gut-brain metabolic signaling.}, journal = {Brain, behavior, and immunity}, volume = {102}, number = {}, pages = {11-22}, doi = {10.1016/j.bbi.2022.02.007}, pmid = {35143877}, issn = {1090-2139}, mesh = {Animals ; Bacteroides ; Brain/metabolism ; Depression/metabolism ; *Depressive Disorder, Major/metabolism ; *Gastrointestinal Microbiome/physiology ; Humans ; Mice ; }, abstract = {Gut microbiome disturbances have been widely implicated in major depressive disorder (MDD), although the identity of causal microbial species and the underlying mechanisms are yet to be fully elucidated. Here we show that Bacteroides species enriched in the gut microbiome from MDD patients differentially impact the susceptibility to depressive behaviors. Transplantation of fecal microbiome from MDD patients into antibiotic-treated mice induced anxiety and despair-like behavior and impaired hippocampal neurogenesis. Colonization of Bacteroides fragilis, Bacteroides uniformis, and, to a lesser extent, Bacteroides caccae, but not Bacteroides ovatus, recapitulated the negative effects of MDD microbiome on behavior and neurogenesis. The varying impacts of Bacteroides species were partially explained by differential alternations of tryptophan pathway metabolites and neurotransmitters along the gut-brain axis. Notably, an intensified depletion of cerebral serotonin concurred with the enhanced susceptibility to depression. Together, these findings identify select Bacteroidetes species that contribute to depression susceptibility in mice by metabolic regulation along the gut-brain axis.}, }
@article {pmid35140882, year = {2022}, author = {Junca, H and Pieper, DH and Medina, E}, title = {The emerging potential of microbiome transplantation on human health interventions.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {615-627}, pmid = {35140882}, issn = {2001-0370}, abstract = {The human microbiome has been the subject of intense research over the past few decades, in particular as a promising area for new clinical interventions. The microbiota colonizing the different body surfaces are of benefit for multiple physiological and metabolic processes of the human host and increasing evidence suggests an association between disturbances in the composition and functionality of the microbiota and several pathological conditions. This has provided a rationale for beneficial modulation of the microbiome. One approach being explored for modulating the microbiota in diseased individuals is transferring microbiota or microbiota constituents from healthy donors via microbiome transplantation. The great success of fecal microbiome transplantation for the treatment of Clostridioides difficile infections has encouraged the application of this procedure for the treatment of other diseases such as vaginal disorders via transplantation of vaginal microbiota, or of skin pathologies via the transplantation of skin microbiota. Microbiome modulation could even become a novel strategy for improving the efficacy of cancer therapies. This review discusses the principle, advantages and limitations of microbiome transplantation as well as different clinical contexts where microbiome transplantation has been applied.}, }
@article {pmid35140783, year = {2022}, author = {Khan, R and Roy, N and Ali, H and Naeem, M}, title = {Fecal Microbiota Transplants for Inflammatory Bowel Disease Treatment: Synthetic- and Engineered Communities-Based Microbiota Transplants Are the Future.}, journal = {Gastroenterology research and practice}, volume = {2022}, number = {}, pages = {9999925}, pmid = {35140783}, issn = {1687-6121}, abstract = {The human intestine harbors a huge number of diverse microorganisms where a variety of complex interactions take place between the microbes as well as the host and gut microbiota. Significant long-term variations in the gut microbiota (dysbiosis) have been associated with a variety of health conditions including inflammatory bowel disease (IBD). Conventional fecal microbiota transplantations (FMTs) have been utilized to treat IBD and have been proved promising. However, various limitations such as transient results, pathogen transfer, storage, and reproducibility render conventional FMT less safe and less sustainable. Defined synthetic microbial communities (SynCom) have been used to dissect the host-microbiota-associated functions using gnotobiotic animals or in vitro cell models. This review focuses on the potential use of SynCom in IBD and its advantages and relative safety over conventional FMT. Additionally, this review reinforces how various technological advances could be combined with SynCom to have a better understanding of the complex microbial interactions in various gut inflammatory diseases including IBD. Some technological advances including the availability of a gut-on-a-chip system, intestinal organoids, ex vivo intestinal cultures, AI-based refining of the microbiome structural and functional data, and multiomic approaches may help in making more practical in vitro models of the human host. Additionally, an increase in the cultured diversity from gut microbiota and the availability of their genomic information would further make the design and utilization of SynCom more feasible. Taken together, the combined use of the available knowledge of the gut microbiota in health and disease and recent technological advances and the development of defined SynCom seem to be a promising, safe, and sustainable alternative to conventional FMT in treating IBD.}, }
@article {pmid35138387, year = {2022}, author = {Tungsanga, S and Katavetin, P and Panpetch, W and Udompornpitak, K and Saisorn, W and Praditpornsilpa, K and Eiam-Ong, S and Tungsanga, K and Tumwasorn, S and Leelahavanichkul, A}, title = {Lactobacillus rhamnosus L34 attenuates chronic kidney disease progression in a 5/6 nephrectomy mouse model through the excretion of anti-inflammatory molecules.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {37}, number = {8}, pages = {1429-1442}, doi = {10.1093/ndt/gfac032}, pmid = {35138387}, issn = {1460-2385}, mesh = {Animals ; Anti-Inflammatory Agents ; Caco-2 Cells ; Culture Media, Conditioned ; Disease Models, Animal ; Fibrosis ; Humans ; Indican ; Inflammation/pathology/prevention &amp; control ; *Lacticaseibacillus rhamnosus ; Mice ; Nephrectomy ; *Renal Insufficiency, Chronic/pathology ; Tumor Necrosis Factor-alpha ; }, abstract = {BACKGROUND: Although pathogenic gut microbiota causes gut leakage, increases translocation of uremic toxins into circulation and accelerates CKD progression, the local strain of Lactobacillus rhamnosus L34 might attenuate gut leakage. We explored the effects of L34 on kidney fibrosis and levels of gut-derived uremic toxins (GDUTs) in 5/6 nephrectomy (5/6Nx) mice.<br><br>METHODS: At 6 weeks post-5/6Nx in mice, either L34 (1&#xa0;&#xd7;&#xa0;106 CFU) or phosphate buffer solution (as 5/6Nx control) was fed daily for 14 weeks. In vitro, the effects of L34-conditioned media with or without indoxyl sulfate (a representative GDUT) on inflammation and cell integrity (transepithelial electrical resistance; TEER) were assessed in Caco-2 (enterocytes). In parallel, the effects on proinflammatory cytokines and collagen expression were assessed in HK2 proximal tubular cells.<br><br>RESULTS: At 20 weeks post-5/6Nx, L34-treated mice showed significantly fewer renal injuries, as evaluated by (i) kidney fibrosis area (P&#xa0;<&#xa0;0.01) with lower serum creatinine and proteinuria, (ii) GDUT including trimethylamine-N-oxide (TMAO) (P&#xa0;=&#xa0;0.02) and indoxyl sulfate (P&#xa0;<&#xa0;0.01) and (iii) endotoxin (P&#xa0;=&#xa0;0.03) and serum TNF-&#x3b1; (P&#xa0;=&#xa0;0.01) than 5/6Nx controls. Fecal microbiome analysis revealed an increased proportion of Bacteroidetes in 5/6Nx controls. After incubation with indoxyl sulfate, Caco-2 enterocytes had higher interleukin-8 and nuclear factor &#x3ba;B expression and lower TEER values, and HK2 cells demonstrated higher gene expression of TNF-&#x3b1;, IL-6 and collagen (types III and IV). These indoxyl sulfate-activated parameters were attenuated with L34-conditioned media, indicating the protective role of L34 in enterocyte integrity and renal fibrogenesis.<br><br>CONCLUSION: L34 attenuated uremia-induced systemic inflammation by reducing GDUTs and gut leakage that provided renoprotective effects in CKD.}, }
@article {pmid35135950, year = {2022}, author = {Sekiguchi, E and Toubai, T and Suto, M and Matsuki, E and Miyata, M and Ishizawa, K}, title = {[Fecal metabolomic profiles in experimental murine bone marrow transplantation].}, journal = {[Rinsho ketsueki] The Japanese journal of clinical hematology}, volume = {63}, number = {1}, pages = {37-44}, doi = {10.11406/rinketsu.63.37}, pmid = {35135950}, issn = {0485-1439}, mesh = {Animals ; Bone Marrow Transplantation ; *Gastrointestinal Microbiome ; *Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation ; Mice ; }, abstract = {Graft-versus-host disease (GVHD) is a life-threating complication of allogeneic hematopoietic cell transplantation (allo-HCT). Prior studies have shown that gastrointestinal (GI) GVHD is associated with a reduction in intestinal microbiota diversity and a change in microbial metabolites. We conducted fecal metabolome analyses using a murine bone marrow transplantation. From this analysis, 290 metabolites were identified; of these, 18 metabolites were significantly or specifically higher and 12 were significantly or specifically lower in the allogeneic group than in the syngeneic one. Particularly, several metabolites in the choline metabolism and tryptophan metabolism were altered in the allogeneic group. Hierarchical clustering analysis demonstrated that the changed metabolites in the allogeneic group had similar profiles. Conclusively, we suggest that alloimmune responses are related to microbial metabolites in recipients receiving allo-HCT. The relationship between metabolites involved in GI GVHD and the intestinal microbiota and its physiological significance warrant further investigations.}, }
@article {pmid35135881, year = {2022}, author = {Jones, EW and Carlson, JM and Sivak, DA and Ludington, WB}, title = {Stochastic microbiome assembly depends on context.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {7}, pages = {}, pmid = {35135881}, issn = {1091-6490}, support = {DP5 OD017851/OD/NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*classification ; Bacterial Physiological Phenomena/genetics ; Drosophila melanogaster/*microbiology ; *Microbiota ; Models, Biological ; Species Specificity ; Stochastic Processes ; }, abstract = {Observational studies reveal substantial variability in microbiome composition across individuals. Targeted studies in gnotobiotic animals underscore this variability by showing that some bacterial strains colonize deterministically, while others colonize stochastically. While some of this variability can be explained by external factors like environmental, dietary, and genetic differences between individuals, in this paper we show that for the model organism Drosophila melanogaster, interactions between bacteria can affect the microbiome assembly process, contributing to a baseline level of microbiome variability even among isogenic organisms that are identically reared, housed, and fed. In germ-free flies fed known combinations of bacterial species, we find that some species colonize more frequently than others even when fed at the same high concentration. We develop an ecological technique that infers the presence of interactions between bacterial species based on their colonization odds in different contexts, requiring only presence/absence data from two-species experiments. We use a progressive sequence of probabilistic models, in which the colonization of each bacterial species is treated as an independent stochastic process, to reproduce the empirical distributions of colonization outcomes across experiments. We find that incorporating context-dependent interactions substantially improves the performance of the models. Stochastic, context-dependent microbiome assembly underlies clinical therapies like fecal microbiota transplantation and probiotic administration and should inform the design of synthetic fecal transplants and dosing regimes.}, }
@article {pmid35130123, year = {2022}, author = {Zhang, X and Walker, K and Mayne, J and Li, L and Ning, Z and Stintzi, A and Figeys, D}, title = {Evaluating live microbiota biobanking using an ex vivo microbiome assay and metaproteomics.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2035658}, pmid = {35130123}, issn = {1949-0984}, mesh = {Bacteria/chemistry/*growth &amp; development/metabolism ; Biological Specimen Banks ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Microbial Viability ; Prebiotics/analysis ; Preservation, Biological/*methods ; Proteomics/*methods ; }, abstract = {Biobanking of live microbiota is becoming indispensable for mechanistic and clinical investigations of drug-microbiome interactions and fecal microbiota transplantation. However, there is a lack of methods to rapidly and systematically evaluate whether the biobanked microbiota maintains their cultivability and functional activity. In this study, we use a rapid ex vivo microbiome assay and metaproteomics to evaluate the cultivability and the functional responses of biobanked microbiota to treatment with a prebiotic (fructo-oligosaccharide, FOS). Our results indicate that the microbiota cultivability and their functional responses to FOS treatment were well maintained by freezing in a deoxygenated glycerol buffer at -80°C for 12 months. We also demonstrate that the fecal microbiota is functionally stable for 48 hours on ice in a deoxygenated glycerol buffer, allowing off-site fecal sample collection and shipping to laboratory for live microbiota biobanking. This study provides a method for rapid evaluation of the cultivability of biobanked live microbiota. Our results show minimal detrimental influences of long-term freezing in deoxygenated glycerol buffer on the cultivability of fecal microbiota.}, }
@article {pmid35127797, year = {2021}, author = {Guo, X and Huang, C and Xu, J and Xu, H and Liu, L and Zhao, H and Wang, J and Huang, W and Peng, W and Chen, Y and Nie, Y and Zhou, Y and Zhou, Y}, title = {Gut Microbiota Is a Potential Biomarker in Inflammatory Bowel Disease.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {818902}, pmid = {35127797}, issn = {2296-861X}, abstract = {Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is characterized by relapse and remission alternately. It remains a great challenge to diagnose and assess disease activity during IBD due to the lack of specific markers. While traditional biomarkers from plasma and stool, such as C-reactive protein (CRP), fecal calprotectin (FC), and S100A12, can be used to measure inflammation, they are not specific to IBD and difficult to determine an effective cut-off value. There is consensus that gut microbiota is crucial for intestinal dysbiosis is closely associated with IBD etiopathology and pathogenesis. Multiple studies have documented differences in the composition of gut microbiota between patients with IBD and healthy individuals, particularly regarding microbial diversity and relative abundance of specific bacteria. Patients with IBD have higher levels of Proteobacteria and lower amounts of Bacteroides, Eubacterium, and Faecalibacterium than healthy individuals. This review summarizes the pros and cons of using traditional and microbiota biomarkers to assess disease severity and treatment outcomes and addresses the possibility of using microbiota-focused interventions during IBD treatment. Understanding the role of microbial biomarkers in the assessment of disease activity and treatment outcomes has the potential to change clinical practice and lead to the development of more personalized therapies.}, }
@article {pmid35127122, year = {2022}, author = {Bakker, GJ and Meijnikman, AS and Scheithauer, TP and Davids, M and Aydin, &#xd6; and Boerlage, TCC and de Brauw, LM and van de Laar, AW and Gerdes, VE and Groen, AK and van Raalte, DH and Herrema, H and Nieuwdorp, M}, title = {Fecal microbiota transplantation does not alter bacterial translocation and visceral adipose tissue inflammation in individuals with obesity.}, journal = {Obesity science &amp; practice}, volume = {8}, number = {1}, pages = {56-65}, pmid = {35127122}, issn = {2055-2238}, abstract = {AIMS: Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation (FMT) on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed.<br><br>MATERIAL AND METHODS: Eight individuals with clinically severe obesity (body mass index [BMI] >35&#xa0;kg/m[2]) and metabolic syndrome received lean donor FMT 4&#xa0;weeks prior to elective bariatric surgery. The participants were age-, sex-, and BMI-matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro-inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation.<br><br>RESULTS: Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro-inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed.<br><br>CONCLUSIONS: Visceral bacterial DNA content and level of inflammation were not altered upon FMT. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity.}, }
@article {pmid35126320, year = {2021}, author = {Vasilescu, IM and Chifiriuc, MC and Pircalabioru, GG and Filip, R and Bolocan, A and Lazăr, V and Diţu, LM and Bleotu, C}, title = {Gut Dysbiosis and Clostridioides difficile Infection in Neonates and Adults.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {651081}, pmid = {35126320}, issn = {1664-302X}, abstract = {In this review, we focus on gut microbiota profiles in infants and adults colonized (CDC) or infected (CDI) with Clostridioides difficile. After a short update on CDI epidemiology and pathology, we present the gut dysbiosis profiles associated with CDI in adults and infants, as well as the role of dysbiosis in C. difficile spores germination and multiplication. Both molecular and culturomic studies agree on a significant decrease of gut microbiota diversity and resilience in CDI, depletion of Firmicutes, Bacteroidetes, and Actinobacteria phyla and a high abundance of Proteobacteria, associated with low butyrogenic and high lactic acid-bacteria levels. In symptomatic cases, microbiota deviations are associated with high levels of inflammatory markers, such as calprotectin. In infants, colonization with Bifidobacteria that trigger a local anti-inflammatory response and abundance of Ruminococcus, together with lack of receptors for clostridial toxins and immunological factors (e.g., C. difficile toxins neutralizing antibodies) might explain the lack of clinical symptoms. Gut dysbiosis amelioration through administration of "biotics" or non-toxigenic C. difficile preparations and fecal microbiota transplantation proved to be very useful for the management of CDI.}, }
@article {pmid35125827, year = {2022}, author = {Hillestad, EMR and van der Meeren, A and Nagaraja, BH and Bjørsvik, BR and Haleem, N and Benitez-Paez, A and Sanz, Y and Hausken, T and Lied, GA and Lundervold, A and Berentsen, B}, title = {Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome.}, journal = {World journal of gastroenterology}, volume = {28}, number = {4}, pages = {412-431}, pmid = {35125827}, issn = {2219-2840}, mesh = {Brain-Gut Axis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; *Microbiota ; }, abstract = {Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal symptoms, recently described as a disturbance of the microbiota-gut-brain axis. Despite decades of research, the pathophysiology of this highly heterogeneous disorder remains elusive. However, a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture. Are we getting any closer to understanding IBS' etiology, or are we drowning in unspecific, conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing? In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota, clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation, neuroimaging and methods in microbiota analyses, and current and future challenges with big data analysis in IBS.}, }
@article {pmid35125404, year = {2022}, author = {Linares-García, L and Cárdenas-Barragán, ME and Hernández-Ceballos, W and Pérez-Solano, CS and Morales-Guzmán, AS and Miller, DS and Schmulson, M}, title = {Bacterial and Fungal Gut Dysbiosis and Clostridium difficile in COVID-19: A Review.}, journal = {Journal of clinical gastroenterology}, volume = {56}, number = {4}, pages = {285-298}, pmid = {35125404}, issn = {1539-2031}, mesh = {*COVID-19/therapy ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Humans ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Gastrointestinal symptoms are common in Coronavirus Disease 2019 (COVID-19), related to infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) of intestinal cells through the angiotensin converting enzyme 2 (ACE2) receptor in the brush border. Also, patients are treated with multiple antibiotics. Therefore, an increase in gut dysbiosis and in the prevalence of Clostridium difficile infection (CDI) is expected in patients with COVID-19.<br><br>METHODS: A PubMed search was conducted using the terms "gut microbiota," "gut mycobiota," "dysbiosis" AND "COVID-19"; "Clostridium difficile," "Clostridioides difficile" AND "COVID-19"; "probiotics," "bacteriotherapy AND COVID-19." Only case series, observational and experimental studies were included.<br><br>RESULTS: A total of 384 papers were retrieved and 21 fulfilled selection criteria. Later, a new paper was identified, thus 22 papers were reviewed. Main findings: (1) gut bacterial dysbiosis has been found in fecal samples of COVID-19 patients, with enrichment of opportunistic organisms and decrease of beneficial commensals such as Faecalibacterium prausnitizii. Dysbiosis is related to inflammatory markers and illness severity. (2) There is evidence for abnormal gut barrier and bacterial translocation with a negative impact in the lungs. (3) Fungal dysbiosis correlating with pulmonary mycobiota, has also been found. (4) There is controversy in the CDI rates among COVID-19 patients versus controls and pandemic versus prepandemic era. (5) There is no available evidence yet to support bacteriotherapy in COVID-19. (6) Fecal microbiota transplantation (FMT) has been proposed for COVID-19, although there is no evidence to support it. Also, FMT can be safely used during the pandemic for CDI if strict screening protocols for donors and fecal product are implemented.<br><br>CONCLUSIONS: In COVID-19 there is bacterial and fungal dysbiosis that correlates with systemic and pulmonary inflammation, and illness severity. Further investigations are warranted to determine the efficacy of bacteriotherapy and FMT for modulating gut dysbiosis in COVID-19.}, }
@article {pmid35124952, year = {2022}, author = {Seth, AK and Jain, P}, title = {Fecal microbiota transplantation for induction of remission, maintenance and rescue in patients with corticosteroid-dependent ulcerative colitis: a long-term follow-up real-world cohort study.}, journal = {Intestinal research}, volume = {20}, number = {2}, pages = {251-259}, pmid = {35124952}, issn = {1598-9100}, abstract = {BACKGROUND/AIMS: To study role of fecal microbiota transplantation (FMT) in induction, maintenance, and rescue in patients with corticosteroid-dependent ulcerative colitis (CDUC).<br><br>METHODS: Patients with active CDUC received 3 fortnightly sessions of colonoscopic induction FMT (iFMT) in addition to standard of care. In patients who achieved clinical remission (CR) or response, prednisolone was tapered from week 4 and azathioprine from week 12. Responders were advised maintenance FMT (mFMT) every 6 months. Those with relapse were offered rescue FMT (rFMT), and low dose prednisolone was added if there was no improvement in 2 weeks.<br><br>RESULTS: All 27 patients enrolled completed iFMT and were followed up for 39 months (range, 9-71 months). The mean Mayo score decreased from 6.4&#xb1;2.5 at baseline to 2.6&#xb1;3.7 at week 4, 2.6&#xb1;3.4 at week 12, and 2.8&#xb1;3.8 at week 24 (P<0.05). Corticosteroid-free CR and clinical response at week 12 were seen in 13 patients (48%) and 1 patient (3.7%), respectively. Corticosteroid and azathioprine-free CR at week 24 was seen in 13 patients (48%) and in them histological response was seen in 2 patients (15.2%) at week 4, 5 patients (38.4%) at week 12, and 10 patients (76.9%) at week 24. First relapse was seen in 10 of 13 responders (76.9%) at a median of 14.8 months (range, 6-34 months) after iFMT and was less frequent in patients on mFMT. Relapse was treated successfully with rFMT alone in 4 patients (40%) and rFMT with low dose steroids in 5 patients (50%).<br><br>CONCLUSIONS: iFMT, mFMT, and rFMT may have a role in treatment of selected patients with CDUC.}, }
@article {pmid35124900, year = {2022}, author = {Haindl, R and Totzauer, L and Kulozik, U}, title = {Preservation by lyophilization of a human intestinal microbiota: influence of the cultivation pH on the drying outcome and re-establishment ability.}, journal = {Microbial biotechnology}, volume = {15}, number = {3}, pages = {886-900}, pmid = {35124900}, issn = {1751-7915}, mesh = {Desiccation ; Freeze Drying/methods ; *Gastrointestinal Microbiome ; Humans ; Hydrogen-Ion Concentration ; }, abstract = {Faecal microbiota transplantation is an emerging medical concept for the treatment of gastrointestinal diseases. This concept, however, has disadvantages as low storability of stool and intensive donor screening. A solution to overcome these problems would be the preservation of an in vitro microbiota through freeze-drying. However, the influence of the entire preservation process, including cultivation and lyophilization, has not been assessed so far. In this study, the influences of the process steps cultivation, drying and re-cultivation were determined with cell count, production of metabolites, microbial composition and diversity in the system as evaluation criteria. All pH conditions resulted in stable, culturable communities after re-cultivation. Cell count, richness, diversity and microbial composition were affected by freeze-drying, but these effects were reversible and vanished during re-cultivation. Hence, the re-cultivated system did not differ from the system before drying. The metabolism, measured by short-chain fatty acids as indicators, showed slight changes due to natural dynamics. Consequently, the cultivation prior to drying was identified to have more influence than the drying itself on the preservation process and therefore the biggest potential for optimization. Hence, the highest similarity with the initial stool sample was obtained with pH 6.0 - 6.5 during cultivation.}, }
@article {pmid35124471, year = {2022}, author = {Chao, X and Lei, Z and Hongqin, L and Ziwei, W and Dechuan, L and Weidong, D and Lu, X and Haitao, C and Bo, Z and Haixing, J and Qinghua, Y}, title = {Faeces from malnourished colorectal cancer patients accelerate cancer progression.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {41}, number = {3}, pages = {632-644}, doi = {10.1016/j.clnu.2022.01.001}, pmid = {35124471}, issn = {1532-1983}, mesh = {Animals ; *Colorectal Neoplasms/complications/metabolism ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; Humans ; *Malnutrition/complications/diagnosis ; Mice ; Mice, Inbred C57BL ; Tumor Microenvironment ; }, abstract = {BACKGROUD: Malnutrition has been confirmed to play an important role in colorectal cancer (CRC) progression via the gut microenvironment. However, the characteristics of the gut microbiota or its potential biological mechanism in CRC remain inconclusive.<br><br>METHODS: In this work, Patient-Generated Subjective Global Assessment (PG-SGA) tool and 16sRNA sequencing were prepared to detect the variation in gut microbiota and the association between nutrition status and gut microbiota. RDA/CCA analysis was used to evaluate the relationship between faecal microbiota from malnourished CRC and clinical nutrition indicators. To investigate the mechanism of the gut microbiota in CRC, faecal samples from malnourished CRC patients were transplanted into C57BL/6J and DSS/AOM mouse models. Moreover, FACS and IHC were prepared to detect the infiltration of B cells and macrophages. qPCR and Elisa assays were performed to explore the expression of cytokines.<br><br>RESULT: We found dramatic variation in the faecal microbiota among patients with different nutritional statuses, discovering that specific microbiota species, namely, Atopobium vaginae, Selenomonas sputigena and Faecalibacterium prausnitzii, may be considered diagnostic biomarkers in malnutrition and indicate poor prognosis. High expression level of A.&#xa0;vaginae in CRC tissues revealed the poorer overall survival compared with low expression level (Mean survival: 23.0 months vs 29.0 months). Faecal from malnourished colorectal cancer were found to be protumorigenic. More importantly, our evidence suggests that after faecal microbiota transplantation, B cells and macrophages are recruited to activate specific tumour immunity in CRC. Depletion of B cells significantly suppressed faecal microbiota-induced M2b polarization as well as the protumorigenic activity of tumour-associated macrophages in&#xa0;vivo.<br><br>CONCLUSION: Faecal microbiota in CRC under malnutrition conditions exhibits specific characteristics that accelerate CRC progression and regulate B cells and macrophages. The use of specific faecal microbial species could be a feasible approach for identifying the malnutrition status of patients and demonstrating the poor prognosis of CRC.}, }
@article {pmid35118227, year = {2022}, author = {Song, YN and Yang, DY and Veldhuyzen van Zanten, S and Wong, K and McArthur, E and Song, CZ and Ianiro, G and Cammarota, G and Kelly, C and Fischer, M and Russell, L and Kao, D}, title = {Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile Infection: Systematic Review and Meta-analysis.}, journal = {Journal of the Canadian Association of Gastroenterology}, volume = {5}, number = {1}, pages = {e1-e11}, pmid = {35118227}, issn = {2515-2092}, abstract = {BACKGROUND: Severe or fulminant Clostridioides difficile infection (SFCDI) is associated with significant morbidity and mortality. Emerging evidence suggests fecal microbiota transplant (FMT) may be a promising therapy for SFCDI.<br><br>AIM: This systematic review determines the safety and efficacy of FMT in medically refractory SFCDI.<br><br>METHODS: A systematic search of the literature was conducted using PubMed (1965 to 2020), Web of Science (1900 to 20), EMBASE (1974 to 2020), and Cochrane Review (1945 to 2020). Quality appraisal by NIH Study Quality Assessment tools, and data extraction were performed by two teams of independent researchers. The primary outcome was resolution of SFCDI 4 weeks after the final FMT. Pooled resolution rates were calculated using generalized linear mixed models estimates.<br><br>RESULTS: Two hundred and forty patients from 10 studies (8 case series, 1 case-control and 1 randomized study) were included with 209 individual patient-level data. FMT resulted in resolution of SFCDI within 4 weeks in 211/240 individuals for a pooled estimate of 88% (95% confidence interval [CI]: 0.83 to 0.91). The mean number of FMT required was 1.6 for severe and 2.0 for fulminant CDI resolution. The pooled proportional estimates for patients requiring CDI-directed antimicrobials after FMT was 50% (95% CI: 0.06 to 0.94) for severe CDI and 67.0% (95% CI: 0.30 to 0.91) for fulminant CDI. Serious adverse event rates were low.<br><br>CONCLUSION: FMT appears effective in treating SFCDI patients with low adverse events, but requires multiple treatments with a significant proportion of patients requiring additional anti-CDI antibiotics to achieve resolution. The optimal route of FMT delivery remains unknown. The presence of pseudomembranous colitis may guide additional FMT or anti-CDI antibiotic treatment.}, }
@article {pmid35116024, year = {2021}, author = {Zhao, ZX and Yuan, X and Cui, YY and Liu, J and Shen, J and Jin, BY and Feng, BC and Zhai, YJ and Zheng, MQ and Kou, GJ and Zhou, RC and Li, LX and Zuo, XL and Li, SY and Li, YQ}, title = {Melatonin Mitigates Oxazolone-Induced Colitis in Microbiota-Dependent Manner.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {783806}, pmid = {35116024}, issn = {1664-3224}, mesh = {Animals ; Colitis, Ulcerative/chemically induced/*metabolism/*microbiology ; Colon/drug effects/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Humans ; Melatonin/*metabolism/*pharmacology ; Mice ; Oxazolone/toxicity ; }, abstract = {Levels of type 2 cytokines are elevated in the blood and intestinal tissues of ulcerative colitis (UC) patients in the active phase; this phenomenon indicates the participation of type 2 immune response in UC progression. The beneficial effects of melatonin in dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis models have been illustrated, but its role in the oxazolone (Oxa)-induced colitis model (driven by type 2 immune response) remains relatively unknown. We investigated the relationship between melatonin concentration and the severity of UC, revealing a significantly negative correlation. Subsequently, we investigated the effects of melatonin in Oxa-induced colitis mice and the potential underlying mechanisms. Administration of melatonin significantly counteracted body weight loss, colon shortening, and neutrophil infiltration in Oxa-induced colitis mice. Melatonin treatment mitigated Oxa-induced colitis by suppressing type 2 immune response. In addition, melatonin attenuated intestinal permeability by enhancing the expression of ZO-1 and occludin in colitis mice. Interestingly, the protective effect of melatonin was abolished when the mice were co-housed, indicating that the regulation of gut microbiota by melatonin was critical in alleviating Oxa-induced colitis. Subsequently, 16S rRNA sequencing was performed to explore the microbiota composition. Decreased richness and diversity of intestinal microbiota at the operational taxonomic unit (OTU) level resulted from melatonin treatment. Melatonin also elevated the abundance of Bifidobacterium, a well-known probiotic, and reduced proportions of several harmful bacterial genera, such as Desulfovibrio, Peptococcaceae, and Lachnospiraceae. Fecal microbiota transplantation (FMT) was used to explore the role of microbiota in the function of melatonin in Oxa-induced colitis. Microbiota transplantation from melatonin-treated mice alleviated Oxa-induced colitis, suggesting that the microbiome participates in the relief of Oxa-induced colitis by melatonin. Our findings demonstrate that melatonin ameliorates Oxa-induced colitis in a microbiota-dependent manner, suggesting the therapeutic potential of melatonin in treating type 2 immunity-associated UC.}, }
@article {pmid35115909, year = {2021}, author = {Yu, X and Fu, X and Wu, X and Tang, W and Xu, L and Hu, L and Xu, C and Zhou, H and Zhou, G and Li, J and Cao, S and Liu, J and Yan, F and Wang, L and Liu, F and Chen, G}, title = {Metformin Alleviates Neuroinflammation Following Intracerebral Hemorrhage in Mice by Regulating Microglia/Macrophage Phenotype in a Gut Microbiota-Dependent Manner.}, journal = {Frontiers in cellular neuroscience}, volume = {15}, number = {}, pages = {789471}, pmid = {35115909}, issn = {1662-5102}, abstract = {The gut microbiota plays a key role in regulating intracerebral hemorrhage (ICH)-induced neuroinflammation. The anti-neuroinflammatory effects of metformin (Met) have been reported in many central nervous system (CNS) diseases. However, whether Met regulates neuroinflammation through the gut microbiota in ICH-induced brain injury remains unknown. We found that Met treatment substantially alleviated neurological dysfunction and reduced neuroinflammation by inhibiting pro-inflammatory polarization of microglia/macrophages in mice with ICH. Moreover, Met treatment altered the microbiota composition and improved intestinal barrier function. The expression of lipopolysaccharide-binding protein (LBP), a biomarker of intestinal barrier damage, was also significantly reduced by Met treatment. Neuroinflammation was also potently ameliorated after the transplantation of fecal microbiota from Met-treated ICH mice. The neuroprotective effects of fecal microbiota transplantation (FMT) were similar to those of oral Met treatment. However, suppression of the gut microbiota negated the neuroprotective effects of Met in ICH mice. Therefore, Met is a promising therapeutic agent for neuroinflammation owing to ICH-induced imbalance of the gut microbiota.}, }
@article {pmid35115674, year = {2022}, author = {Kim, ES and Yoon, BH and Lee, SM and Choi, M and Kim, EH and Lee, BW and Kim, SY and Pack, CG and Sung, YH and Baek, IJ and Jung, CH and Kim, TB and Jeong, JY and Ha, CH}, title = {Fecal microbiota transplantation ameliorates atherosclerosis in mice with C1q/TNF-related protein 9 genetic deficiency.}, journal = {Experimental &amp; molecular medicine}, volume = {54}, number = {2}, pages = {103-114}, pmid = {35115674}, issn = {2092-6413}, support = {H23 IP000687/IP/NCIRD CDC HHS/United States ; R43 IP000011/IP/NCIRD CDC HHS/United States ; }, mesh = {Adiponectin/genetics/metabolism ; Animals ; *Atherosclerosis/genetics/therapy ; Complement C1q ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Glycoproteins/genetics/metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; }, abstract = {Despite the strong influence of the gut microbiota on atherosclerosis, a causal relationship between atherosclerosis pathophysiology and gut microbiota is still unverified. This study was performed to determine the impact of the gut microbiota on the pathogenesis of atherosclerosis caused by genetic deficiency. To elucidate the influence of the gut microbiota on atherosclerosis pathogenesis, an atherosclerosis-prone mouse model (C1q/TNF-related protein 9-knockout (CTRP9-KO) mice) was generated. The gut microbial compositions of CTRP9-KO and WT control mice were compared. Fecal microbiota transplantation (FMT) was performed to confirm the association between gut microbial composition and the progression of atherosclerosis. FMT largely affected the gut microbiota in both CTRP9-KO and WT mice, and all transplanted mice acquired the gut microbiotas of the donor mice. Atherosclerotic lesions in the carotid arteries were decreased in transplanted CTRP9-KO mice compared to CTRP9-KO mice prior to transplantation. Conversely, WT mice transplanted with the gut microbiotas of CTRP9-KO mice showed the opposite effect as that of CTRP9-KO mice transplanted with the gut microbiotas of WT mice. Here, we show that CTRP9 gene deficiency is related to the distribution of the gut microbiota in subjects with atherosclerosis. Transplantation of WT microbiotas into CTRP9-KO mice protected against the progression of atherosclerosis. Conversely, the transplantation of CTRP9-KO microbiotas into WT mice promoted the progression of atherosclerosis. Treating atherosclerosis by restoring gut microbial homeostasis may be an effective therapeutic strategy.}, }
@article {pmid35111693, year = {2021}, author = {Xi, S and Wang, Y and Wu, C and Peng, W and Zhu, Y and Hu, W}, title = {Intestinal Epithelial Cell Exosome Launches IL-1β-Mediated Neuron Injury in Sepsis-Associated Encephalopathy.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {783049}, pmid = {35111693}, issn = {2235-2988}, mesh = {Animals ; Epithelial Cells ; *Exosomes ; Fecal Microbiota Transplantation ; Neurons ; Rats ; *Sepsis-Associated Encephalopathy ; }, abstract = {BACKGROUND: Gut-microbiota-brain axis links the relationship between intestinal microbiota and sepsis-associated encephalopathy (SAE). However, the key mediators between them remain unclear.<br><br>METHODS: Memory test was determined by Water maze. Intestinal flora was measured by 16S RNA sequencing. Neurotransmitter was detected by high-performance liquid chromatography (HPLC). Histopathology was determined by H&amp;E, immunofluorescence (IF), and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining. Flow cytometry was employed to determine the proportion of macrophages.<br><br>RESULTS: Fecal microbiota transplantation (FMT) relieved hippocampus impairment of SAE rats by inhibiting inflammation cytokine secretion, the expression of IBA-1 and neurotransmitter disturbance, and cell apoptosis and autophagy, accompanied by the reduced M1 polarization and M1 pro-inflammation factors produced by macrophages in mesenteric lymph nodes (MLNs). Actually, M1 polarization in SAE rats depended on intestinal epithelial cell (IEC)-derived exosome. GW4869-initiated inhibition of exosome secretion notably abolished M1 polarization and the secretion of IL-1&#x3b2;. However, GW4869-mediated improvement of hippocampus impairment was counteracted by the delivery of recombinant interleukin (IL)-1&#x3b2; to hippocampus. Mechanistically, IEC-derived exosome induced the excessive circulating IL-1&#x3b2; produced by CP-R048 macrophages, which subsequently induced damage and apoptosis of hippocampal neurons H19-7 in an autophagy-dependent manner. And reactivation of autophagy facilitates intestinal IL-1&#x3b2;-mediated hippocampal neuron injury.<br><br>CONCLUSION: Collectively, intestinal flora disturbance induced the exosome release of IECs, which subsequently caused M1 polarization in MLNs and the accumulation of circulating IL-1&#x3b2;. Circulating IL-1&#x3b2; promoted the damage and apoptosis of neurons in an autophagy-dependent manner. Possibly, targeting intestinal flora or IEC-derived exosome contributes to the treatment of SAE.}, }
@article {pmid35111551, year = {2021}, author = {Osaki, H and Jodai, Y and Koyama, K and Omori, T and Horiguchi, N and Kamano, T and Funasaka, K and Nagasaka, M and Nakagawa, Y and Shibata, T and Ohmiya, N}, title = {Clinical response and changes in the fecal microbiota and metabolite levels after fecal microbiota transplantation in patients with inflammatory bowel disease and recurrent Clostridioides difficile infection.}, journal = {Fujita medical journal}, volume = {7}, number = {3}, pages = {87-98}, pmid = {35111551}, issn = {2189-7255}, abstract = {OBJECTIVES: We determined the efficacy of fecal microbiota transplantation (FMT) and subsequent changes in fecal microbiota and short-chain fatty acid (SCFA) levels in patients with ulcerative colitis (UC), Crohn's disease (CD), and recurrent Clostridioides difficile infection (rCDI).<br><br>METHODS: A filtered solution of Japanese donor feces was endoscopically administered. The efficacy of FMT was evaluated after 8 weeks using the Mayo score, Crohn's Disease Activity Index (CDAI), and the absence of diarrhea with stool toxin negativity in patients with active UC, CD, and rCDI, respectively. For fecal microbiota analysis, the 16S ribosomal RNA gene was sequenced, and fecal SCFA levels were measured.<br><br>RESULTS: Clinical response was achieved in 5/20 (25%), 3/4 (75%), and 4/4 (100%) patients with UC, CD, and rCDI, respectively. Clinical remission was achieved in 4/20 (20%) and 1/4 (25%) patients with UC and CD, respectively. Linear discriminant analysis illustrated that UC responders had lower counts of Clostridium cluster XIVa before FMT and higher counts after FMT. Higher Fusicatenibacter saccharivorans counts in donors were significantly correlated with 8-week clinical remission. Patients with CD exhibited lower Blautia, Dorea, and Eubacterium counts before FMT and higher Collinsella, Dorea, and Eubacterium counts after FMT, accompanied by functional profiles predictive of SCFA fermentation and elevated fecal butyrate concentrations. Patients with rCDI displayed significantly lower abundances of Clostridium clusters IV and XIVa before FMT and higher abundances after FMT accompanied by elevated fecal propionate concentrations.<br><br>CONCLUSIONS: FMT exhibited various efficacy against UC, CD, and rCDI by altering the gut microbiota and SCFA production.}, }
@article {pmid35108315, year = {2022}, author = {Liu, L and Fu, Q and Li, T and Shao, K and Zhu, X and Cong, Y and Zhao, X}, title = {Gut microbiota and butyrate contribute to nonalcoholic fatty liver disease in premenopause due to estrogen deficiency.}, journal = {PloS one}, volume = {17}, number = {2}, pages = {e0262855}, pmid = {35108315}, issn = {1932-6203}, mesh = {Adult ; Animals ; Butyrates/*metabolism ; Defensins/genetics/metabolism ; Disease Models, Animal ; Estrogens/deficiency/*metabolism ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/cytology/metabolism ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Non-alcoholic Fatty Liver Disease/metabolism/*pathology/therapy ; Ovariectomy ; Premenopause ; Triglycerides/blood ; Zonula Occludens-1 Protein/genetics/metabolism ; }, abstract = {The incidence of nonalcoholic fatty liver disease (NAFLD) in postmenopausal women has increased significantly. Estrogen plays a very important role in NAFLD, but whether NAFLD in premenopausal women was caused by estrogen deficiency was unknown. Thus, it is of great clinical significance to explore the mechanism of NAFLD in premenopausal women. Gut microbiota and its metabolites short chain fatty acids (SCFA) have been shown to play important roles in the development of NAFLD. In this study, we investigated the impact of gut microbiota and SCFA in NAFLD patients and mice caused by estrogen deficiency. We showed that premenopause NAFLD patients had much lower estrogen levels. Estrogen deficient mice, due to ovariectomy (OVX), suffered more severe liver steatosis with an elevated body weight, abdominal fat weight, serum triglycerides and deterioration in hepatic steatosis. Altered gut microbiota composition and decreased butyrate content were found in NAFLD patients and in OVX mice. Furthermore, fecal microbiota transplantation (FMT) or supplementing with butyrate alleviated NAFLD in OVX mice. The production of antimicrobial peptides (AMP) Reg3ɣ, β-defensins and the expression of intestinal epithelial tight junction, including ZO-1 and Occluding-5, were decreased in the OVX mice compared to control mice. Upregulation of PPAR-ɣ and VLDLR, downregulation of PPAR-ɑ indicated that OVX mice suffered from abnormal lipid metabolism. These data indicate that changes in the gut microbiota and SCFA caused by estrogen reduction, together with a disorder in AMP production and lipid metabolism, promote NAFLD, thus provide SCFAs derived from microbiota as new therapeutic targets for the clinical prevention and treatment of NAFLD.}, }
@article {pmid35108241, year = {2022}, author = {Elhusein, AM and Fadlalmola, HA}, title = {Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome Patients: An Updated Systematic Review and Meta-Analysis.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {45}, number = {1}, pages = {11-20}, pmid = {35108241}, issn = {1538-9766}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; Quality of Life ; }, abstract = {Irritable bowel syndrome (IBS) is a chronic gastrointestinal disease characterized by abdominal discomfort and bloating, diarrhea, and/or constipation. Fecal microbiota transplantation (FMT) is transferring the fecal bacteria and other microorganisms from a healthy person to another. We performed this systematic review and meta-analysis to assess the efficacy of FMT in treating IBS patients. We searched Scopus, PubMed, Cochrane, and Web of Science databases through June 2021 using relevant key words. We included 19 studies. Fecal microbiota transplantation was significantly superior to placebo in IBS quality of life after 4 weeks (mean difference [MD] = 7.47, 95% confidence interval [CI]: 2.05-12.89, p = .04), 12 weeks (MD = 9.99, 95% CI: 5.78-14.19, p < .00001), and 24 weeks (MD = 8.49, 95% CI: 0.47-16.52, p = .04), with no difference regarding IBS improvement symptoms and the IBS Severity Scoring System (SSS). Single-arm analysis revealed that the incidence of improvement of IBS symptoms was 57.8% (45.6%-69.9%) with reduction in IBS-SSS (MD = -74, 95% CI: -101.7 to -46.3). Fecal microbiota transplantation was superior to placebo in improving quality of life after 4, 12, and 24 weeks. Also, FMT improved IBS symptoms and reduced the IBS-SSS score. However, no deference was detected between FMT and placebo in IBS-SSS score and IBS symptoms improvement.}, }
@article {pmid35105621, year = {2022}, author = {Chen, Y and Xueying, Z and Jiaqu, C and Qiyi, C and Huanlong, Q and Ning, L and Yasong, D and Xiaoxin, Z and Rong, Y and Jubao, L and Xiaoqiong, L and Chunlian, M and Yu, W and Shidong, C and Guifang, K and Dongmei, Z and Shuanfeng, F and Xujing, Z and Binrang, Y and Yanxia, W and Ling, L and Song, Y and Xiang, Z and Beihua, Z and Lin, J and Hong, J and , }, title = {FTACMT study protocol: a multicentre, double-blind, randomised, placebo-controlled trial of faecal microbiota transplantation for autism spectrum disorder.}, journal = {BMJ open}, volume = {12}, number = {1}, pages = {e051613}, pmid = {35105621}, issn = {2044-6055}, mesh = {*Autism Spectrum Disorder/etiology/therapy ; Child ; Child, Preschool ; Double-Blind Method ; Fecal Microbiota Transplantation/methods ; Feces ; *Gastrointestinal Microbiome ; Humans ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: Autism spectrum disorder (ASD) is a complicated diffuse developmental disorder that commonly involves gastrointestinal distress and dysbacteriosis. Emerging lines of evidence have shown faecal microbiota transplantation (FMT) to be a potential therapeutic strategy for improving the clinical outcomes of patients with ASD by re-establishing their intestinal microflora. We are undertaking the first-ever multicentre, double-blind, randomised controlled trial of FMT for the treatment of children with both ASD and gastrointestinal symptoms and will assess the feasibility and efficacy outcomes of this strategy.<br><br>METHODS: In total, 318 children with both ASD and gastrointestinal symptoms will be enrolled (from 15 hospitals in China) to receive either FMT intervention (n=212) or a placebo (control, n=106). Children aged 3-6 years will take two capsules two times a day, and those older than 6 years will take three capsules two times a day. Each patient will receive four treatment courses, with each 12-day course being repeated every month. Outcomes will be evaluated at baseline, throughout the period of intervention, and at subsequent follow-ups for 2 months. The primary trial objective is to investigate the remodelling effect of FMT on the intestinal microflora in patients with ASD. The secondary objective focuses on the clinical efficacy and safety of FMT, including its improvement of the clinical response and metabonomics.<br><br>ETHICS AND DISSEMINATION: Ethical approval was obtained from the hospital Ethics Committee of each Faecal Transfer for ASD China Multicenter Trial Working Group. The ongoing FMT clinical trial is intended to support the approval of the new technology and its administration. The results of this trial will provide high-quality evidence to inform the future clinical application of this new therapy.<br><br>TRIAL REGISTRATION NUMBER: ChiCTR2100043906; Pre-results.}, }
@article {pmid35104764, year = {2022}, author = {Zhou, H and Zhao, J and Liu, C and Zhang, Z and Zhang, Y and Meng, D}, title = {Xanthoceraside exerts anti-Alzheimer's disease effect by remodeling gut microbiota and modulating microbial-derived metabolites level in rats.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {98}, number = {}, pages = {153937}, doi = {10.1016/j.phymed.2022.153937}, pmid = {35104764}, issn = {1618-095X}, abstract = {BACKGROUND: Microbial-derived metabolites play important roles in Alzheimer's disease (AD) pathology, yet how intestinal microbes influence AD progression remains uncertain. Xanthoceraside (XAN), a triterpenoid saponin with anti-AD activity, was extracted from the husks of Xanthoceras sorbifolia Bunge. However, it is still unclear that how XAN modulates the gut microbiota community to regulate AD progression through changing the levels of microbial-derived metabolites.<br><br>PURPOSE: In this study, we investigated the mechanism underlying the anti-AD effect of XAN.<br><br>METHODS: The current combination studies of multiple-targeted metabolomics, natural product chemistry and pharmacology revealed that oral XAN mediated intestinal microbiota to ameliorate A&#x3b2;1-42-induced learning and memory deficits in rats, which were confirmed through antibiotic treatments and fecal microbiota transplantation.<br><br>RESULTS: As a poor water solubility and low permeability compound that hardly be absorbed into blood-brain barrier, XAN significantly regulated A&#x3b2;1-42-induced metabolism disorders directly or indirectly in gut, including neurotransmitters, amino acids, bile acids and SCFAs metabolism that were detected by UHPLC-MS/MS and GC-MS/MS. In particularly, the in vitro evaluation of XAN on SCFAs production not only found a striking increase in the production of SCFAs after fermentation, but revealed the inner relationship among XAN, gut microbiota and SCFAs in vivo. All results demonstrated that XAN could improve AD rats' learning and memory deficits by modulating the community of gut microbiota which was connected through 16S rRNA sequencing and CCA analyses.<br><br>CONCLUSIONS: Our study provided a novel mechanism for developing XAN as a potential anti-AD drug and revealed that the gut microbiota might be a potential target for AD treatment .}, }
@article {pmid35096856, year = {2021}, author = {Savigamin, C and Mahakit, N and Stithit, S and Samuthpongtorn, C}, title = {How to Initiate Fecal Microbiota Transplantation in Developing Countries Using the Behavior Economics Concept of "Choice Architecture".}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {746230}, pmid = {35096856}, issn = {2296-858X}, }
@article {pmid35094316, year = {2022}, author = {Abuaish, S and Al-Otaibi, NM and Aabed, K and Abujamel, TS and Alzahrani, SA and Alotaibi, SM and Bhat, RS and Arzoo, S and Algahtani, N and Moubayed, NM and El-Ansary, A}, title = {The Efficacy of Fecal Transplantation and Bifidobacterium Supplementation in Ameliorating Propionic Acid-Induced Behavioral and Biochemical Autistic Features in Juvenile Male Rats.}, journal = {Journal of molecular neuroscience : MN}, volume = {72}, number = {2}, pages = {372-381}, pmid = {35094316}, issn = {1559-1166}, support = {RGP-1441-0027//This research project was funded by the Deanship of Scientific Research, Princess Nourah Bint Abdulrahman University, Grant number RGP-1441-0027/ ; }, mesh = {Animals ; *Autistic Disorder ; Behavior, Animal/drug effects ; *Bifidobacterium ; Dietary Supplements ; *Fecal Microbiota Transplantation ; Male ; Oxytocin/metabolism ; *Propionates/pharmacology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Gut microbiota plays a major role in neurological disorders, including autism. Modulation of the gut microbiota through fecal microbiota transplantation (FMT) or probiotic administration, such as Bifidobacteria, is suggested to alleviate autistic symptoms; however, their effects on the brain are not fully examined. We tested both approaches in a propionic acid (PPA) rodent model of autism as treatment strategies. Autism was induced in Sprague-Dawley rats by administering PPA orally (250 mg/kg) for 3 days. Animals were later treated with either saline, FMT, or Bifidobacteria for 22 days. Control animals were treated with saline throughout the study. Social behavior and selected brain biochemical markers related to stress hormones, inflammation, and oxidative stress were assessed. PPA treatment induced social impairments, which was rescued by the treatments. In the brain, Bifidobacteria treatment increased oxytocin relative to control and PPA groups. Moreover, Bifidobacteria treatment rescued the PPA-induced increase in IFN-γ levels. Both treatments increased GST levels, which was diminished by the PPA treatment. These findings indicate the potential of gut microbiota-targeted therapeutics in ameliorating behavioral deficit and underlying neural biochemistry.}, }
@article {pmid35093952, year = {2022}, author = {Gallo, A and Macerola, N and Favuzzi, AM and Nicolazzi, MA and Gasbarrini, A and Montalto, M}, title = {The Gut in Heart Failure: Current Knowledge and Novel Frontiers.}, journal = {Medical principles and practice : international journal of the Kuwait University, Health Science Centre}, volume = {31}, number = {3}, pages = {203-214}, pmid = {35093952}, issn = {1423-0151}, mesh = {*Cardiovascular Diseases ; *Gastrointestinal Microbiome/physiology ; *Heart Failure/therapy ; Humans ; *Microbiota/physiology ; }, abstract = {Heart failure (HF) represents a major health problem affecting millions of people worldwide. In the latest years, many efforts have been made to search for more effective strategies to prevent and modify the course of this disease, but results are still not satisfying. HF represents a complex clinical syndrome involving many other systems, including the gastrointestinal system. Although the relationship between the gut and HF is far from being fully understood, based on recent evidence highlighting the putative role of the gastrointestinal system in different cardiovascular diseases, it is conceivable that the gut-heart link may represent the basis for novel therapeutic approaches in the HF context as well. This intricate interplay involving typical hemodynamic changes and their consequences on gut morphology, permeability, and function, sets the stage for alterations in microbiota composition and is able to impact mechanisms of HF through different routes such as bacterial translocation and metabolic pathways. Thus, the modulation of the gut microbiota through diet, probiotics, and fecal transplantation has been suggested as a potential therapeutic approach. More interestingly, another effect of alteration in microbiota composition reflects in the upregulation of cotransporters (NHE3) with consequent salt and fluid overload and worsening visceral congestion. Therefore, the inhibitors of this cotransporter may also represent a novel therapeutic frontier. By review of recent data on this topic, we describe the current state of the complex interplay between the gastrointestinal and cardiac systems in HF, and the relevance of this knowledge in seeking new therapeutic strategies.}, }
@article {pmid35093183, year = {2022}, author = {Hyun, J and Lee, SK and Cheon, JH and Yong, DE and Koh, H and Kang, YK and Kim, MH and Sohn, Y and Cho, Y and Baek, YJ and Kim, JH and Ahn, JY and Jeong, SJ and Yeom, JS and Choi, JY}, title = {Faecal microbiota transplantation reduces amounts of antibiotic resistance genes in patients with multidrug-resistant organisms.}, journal = {Antimicrobial resistance and infection control}, volume = {11}, number = {1}, pages = {20}, pmid = {35093183}, issn = {2047-2994}, mesh = {Adult ; Aged ; Bacteria/*genetics ; Carbapenem-Resistant Enterobacteriaceae/genetics ; *Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation/*statistics &amp; numerical data ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Republic of Korea ; Vancomycin-Resistant Enterococci/genetics ; Young Adult ; }, abstract = {BACKGROUND: Multidrug-resistant organisms (MDROs) such as vancomycin-resistant enterococci (VRE) and carbapenemase-producing Enterobacteriaceae (CPE) are associated with prolonged hospitalisation, increased medical costs, and severe infections. Faecal microbiota transplantation (FMT) has emerged as an important strategy for decolonisation. This study aimed to evaluate the genetic response of MDROs to FMT.<br><br>METHODS: A single-centre prospective study was conducted on patients infected with VRE, CPE, or VRE/CPE who underwent FMT between May 2018 and April 2019. Genetic response was assessed as the change in the expression of the resistance genes VanA, blaKPC, blaNDM, and blaOXA on days 1, 7, 14, and 28 by real-time reverse-transcription polymerase chain reaction.<br><br>RESULTS: Twenty-nine patients received FMT, of which 26 (59.3%) were infected with VRE, 5 (11.1%) with CPE, and 8 (29.6%) with VRE/CPE. The mean duration of MDRO carriage before FMT was 71&#xa0;days. Seventeen patients (63.0%) used antibiotics within a week of FMT. In a culture-dependent method, the expression of VanA and overall genes significantly decreased (p&#x2009;=&#x2009;0.011 and p&#x2009;=&#x2009;0.003 respectively). In a culture-independent method, VanA, blaNDM, and overall gene expression significantly decreased over time after FMT (p&#x2009;=&#x2009;0.047, p&#x2009;=&#x2009;0.048, p&#x2009;=&#x2009;0.002, respectively). Similar results were confirmed following comparison between each time point in both the culture-dependent and -independent methods. Regression analysis did not reveal important factors underlying the genetic response after FMT. No adverse events were observed.<br><br>CONCLUSION: FMT in patients infected with MDROs downregulates the expression of resistance genes, especially VanA, and facilitates MDRO decolonisation.}, }
@article {pmid35092426, year = {2022}, author = {Guzzo, GL and Andrews, JM and Weyrich, LS}, title = {The Neglected Gut Microbiome: Fungi, Protozoa, and Bacteriophages in Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {28}, number = {7}, pages = {1112-1122}, pmid = {35092426}, issn = {1536-4844}, mesh = {Bacteria/genetics ; *Bacteriophages/genetics ; Dysbiosis/therapy ; Fungi ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/microbiology/therapy ; }, abstract = {The gut microbiome has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Studies suggest that the IBD gut microbiome is less diverse than that of the unaffected population, a phenomenon often referred to as dysbiosis. However, these studies have heavily focused on bacteria, while other intestinal microorganisms-fungi, protozoa, and bacteriophages-have been neglected. Of the nonbacterial microbes that have been studied in relation to IBD, most are thought to be pathogens, although there is evidence that some of these species may instead be harmless commensals. In this review, we discuss the nonbacterial gut microbiome of IBD, highlighting the current biases, limitations, and outstanding questions that can be addressed with high-throughput DNA sequencing methods. Further, we highlight the importance of studying nonbacterial microorganisms alongside bacteria for a comprehensive view of the whole IBD biome and to provide a more precise definition of dysbiosis in patients. With the rise in popularity of microbiome-altering therapies for the treatment of IBD, such as fecal microbiota transplantation, it is important that we address these knowledge gaps to ensure safe and effective treatment of patients.}, }
@article {pmid35091345, year = {2022}, author = {Wortelboer, K and Bakker, GJ and Winkelmeijer, M and van Riel, N and Levin, E and Nieuwdorp, M and Herrema, H and Davids, M}, title = {Fecal microbiota transplantation as tool to study the interrelation between microbiota composition and miRNA expression.}, journal = {Microbiological research}, volume = {257}, number = {}, pages = {126972}, doi = {10.1016/j.micres.2022.126972}, pmid = {35091345}, issn = {1618-0623}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome/genetics ; Humans ; *MicroRNAs/genetics ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {The intestinal gut microbiota is important for human metabolism and immunity and can be influenced by many host factors. A recently emerged host factor is secreted microRNA (miRNA). Previously, it has been shown that secreted miRNAs can influence the growth of certain bacteria and conversely, that shifts in the microbiota can alter the composition of secreted miRNAs. Here, we sought to further investigate the interaction between the gut microbiota and secreted miRNAs by the use of fecal microbiota transplantation (FMT). Subjects with the metabolic syndrome received either an autologous (n = 4) or allogenic (n = 14) FMT. Fecal samples were collected at baseline and 6 weeks after FMT, from which the microbiome and miRNA composition were determined via 16S rRNA sequencing and miRNA sequencing, respectively. We observed a significant correlation between the fecal miRNA expression and microbiota composition, both before and after FMT. Our results suggest that the FMT-induced shift in microbiota altered the fecal miRNA profile, indicated by correlations between differentially abundant microbes and miRNAs. This idea of a shift in miRNA composition driven by changes in the microbiota was further strengthened by the absence of a direct effect of specific miRNAs on the growth of specific bacterial strains.}, }
@article {pmid35090836, year = {2022}, author = {Mu, C and Choudhary, A and Mayengbam, S and Barrett, KT and Rho, JM and Shearer, J and Scantlebury, MH}, title = {Seizure modulation by the gut microbiota and tryptophan-kynurenine metabolism in an animal model of infantile spasms.}, journal = {EBioMedicine}, volume = {76}, number = {}, pages = {103833}, pmid = {35090836}, issn = {2352-3964}, mesh = {Animals ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Humans ; Kynurenine/metabolism/therapeutic use ; Rats ; Seizures ; Spasm ; *Spasms, Infantile/drug therapy/therapy ; Tryptophan/metabolism ; }, abstract = {BACKGROUND: The infantile spasms syndrome is an early-onset epileptic encephalopathy presenting in the first 2 years of life, often with severe developmental consequences. The role of the gut microbiota and metabolism in infantile spasms remains unexplored.<br><br>METHODS: Employing a brain injury neonatal rat model of infantile spasms intractable to anticonvulsant medication treatments, we determined how the ketogenic diet and antibiotics affected specific microbial communities and the resultant circulating factors that confer spasms protection in the infantile spasms model. To confirm a role of kynurenine metabolism pathway in spasms protection, indoleamine 2,3-dioxygenase 1 was pharmacologically inhibited and comprehensive metabolomics was applied.<br><br>FINDINGS: We show that antibiotics reduced spasms and improved the effectiveness of the ketogenic diet when given in combination. Examination of the gut microbiota and metabolomics showed the downregulation of indoleamine 2,3-dioxygenase 1 and upregulation of hippocampal kynurenic acid, a metabolite with antiepileptic effects. To further test the involvement of indoleamine 2,3-dioxygenase 1, a specific antagonist 1-methyltryptophan and minocycline, an antibiotic and inhibitor of kynurenine formation from tryptophan, were administered, respectively. Both treatments were effective in reducing spasms and elevating hippocampal kynurenic acid. A fecal microbiota transplant experiment was then performed to examine the contribution of the gut microbiota on spasm mitigation. Transplant of feces of ketogenic diet animals into normal diet animals was effective in reducing spasms.<br><br>INTERPRETATION: These results highlight the importance of tryptophan-kynurenine metabolism in infantile spasms and provide evidence for new-targeted therapies such as indoleamine 2,3-dioxygenase 1 inhibition or microbiota manipulation to promote kynurenic acid production as a strategy to reduce spasms in infantile spasms.<br><br>FUNDING: This study was funded by the Alberta Children's Hospital Research Institute and the Owerko Centre.}, }
@article {pmid35088703, year = {2022}, author = {Cold, F and Svensson, CK and Christensen, AH and Günther, S and Petersen, AM and Hansen, LH and Helms, M}, title = {Successful treatment of Clostridioidesdifficile infection with single-donorfaecal microbiota transplantation capsules.}, journal = {Danish medical journal}, volume = {69}, number = {2}, pages = {}, pmid = {35088703}, issn = {2245-1919}, mesh = {Capsules ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Humans ; *Microbiota ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {INTRODUCTION: Treatment of recurrent Clostridioides difficile infection with faecal microbiota transplantation (FMT) is highly effective and is the recommended treatment following a second recurrence. The cure rates of capsule treatment are high (82%-88%). Whether using multi-donor or single-donor FMT capsules affects cure rates remains incompletely understood.<br><br>METHODS: A retrospective case series of patients with recurrent, refractory or fulminant C. difficile infection treated for three days with single-donor FMT capsules from October to December 2020 was conducted. The aim of the study was to investigate the clinical efficacy (cure rate) of the treatment and to compare cure rates with previously reported cure rates of treatment with multi-donor FMT capsules produced at the same stool bank. Clinical cure was defined as absence of diarrhoea or diarrhoea with a C. difficile negative stool sample eight weeks after treatment.<br><br>RESULTS: Clinical cure was observed in 15 of the 18 (83.3%) patients following three days of FMT capsule treatment. Cure rates were comparable (p = 1.0) to previously reported cure rates (88.9%) of multi-donor FMT capsule treatment of recurrent C. difficile infection.<br><br>CONCLUSIONS: Three days of single-donor FMT capsule treatment was effective and safe in the treatment of recurrent, refractory and fulminant C. difficile infection with cure rates comparable to those of multi-donor FMT capsule treatment.<br><br>FUNDING: This work was supported by the Danish Innovation Fund under Grant 7076-00129B, MICROHEALTH. The funders had no role in the study design, data collection or analysis, the decision to publish, or in the preparation of the manuscript. The FMT capsules from the Aleris-Hamlet FMT Stool Bank were supplied to the Copenhagen University Hospital - Hvidovre Hospital free of charge.<br><br>TRIAL REGISTRATION: not relevant.}, }
@article {pmid35088527, year = {2022}, author = {Li, XL and Cui, JJ and Zheng, WS and Zhang, JL and Li, R and Ma, XL and Lin, M and Guo, HH and Li, C and Yu, XY and Du, P and Zhao, LM and He, S and Lan, P and Jiang, JD and Che, Y and Wang, LL}, title = {Bicyclol Alleviates Atherosclerosis by Manipulating Gut Microbiota.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {18}, number = {9}, pages = {e2105021}, doi = {10.1002/smll.202105021}, pmid = {35088527}, issn = {1613-6829}, mesh = {Animals ; *Atherosclerosis/drug therapy ; Biphenyl Compounds/pharmacology/therapeutic use ; Dysbiosis ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; }, abstract = {Atherosclerosis (AS) is associated with high morbidity and mortality, thus imposing a growing burden on modern society. Herb-derived bicyclol (BIC) is a versatile bioactive compound that can be used to treat AS. However, its efficacy in AS is not yet described. Here, it is shown that BIC normalizes gut microflora dysbiosis induced by a high fat diet in Apoe[(-/-)] mice. Metagenome-wide association study analysis verifies that the modulation on carbohydrate-active enzymes and short-chain fatty acid generating genes in gut flora is among the mechanisms. The gut healthiness, especially the gut immunity and integrity, is restored by BIC intervention, leading to improved systemic immune cell dynamic and liver functions. Accordingly, the endothelial activation, macrophage infiltration, and cholesterol ester accumulation in the aortic arch are alleviated by BIC to lessen the plaque onset. Moreover, it is proved that the therapeutic effect of BIC on AS is transmissible by fecal microbiota transplantation. The current study, for the first time, demonstrates the antiatherosclerotic effects of BIC and shows that its therapeutic value can at least partially be attributed to its manipulation of gut microbiota.}, }
@article {pmid35087228, year = {2022}, author = {Mills, RH and Dulai, PS and Vázquez-Baeza, Y and Sauceda, C and Daniel, N and Gerner, RR and Batachari, LE and Malfavon, M and Zhu, Q and Weldon, K and Humphrey, G and Carrillo-Terrazas, M and Goldasich, LD and Bryant, M and Raffatellu, M and Quinn, RA and Gewirtz, AT and Chassaing, B and Chu, H and Sandborn, WJ and Dorrestein, PC and Knight, R and Gonzalez, DJ}, title = {Multi-omics analyses of the ulcerative colitis gut microbiome link Bacteroides vulgatus proteases with disease severity.}, journal = {Nature microbiology}, volume = {7}, number = {2}, pages = {262-276}, pmid = {35087228}, issn = {2058-5276}, support = {P30 DK120515/DK/NIDDK NIH HHS/United States ; P30 NS047101/NS/NINDS NIH HHS/United States ; T32 DK007202/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Animals ; Bacterial Proteins/classification/genetics ; Bacteroides/enzymology/*pathogenicity ; Cohort Studies ; Colitis, Ulcerative/*microbiology/*physiopathology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Longitudinal Studies ; Male ; Metagenome ; Metagenomics/*methods ; Mice ; Middle Aged ; Peptide Hydrolases/classification/*genetics ; Proteomics/*methods ; Severity of Illness Index ; }, abstract = {Ulcerative colitis (UC) is driven by disruptions in host-microbiota homoeostasis, but current treatments exclusively target host inflammatory pathways. To understand how host-microbiota interactions become disrupted in UC, we collected and analysed six faecal- or serum-based omic datasets (metaproteomic, metabolomic, metagenomic, metapeptidomic and amplicon sequencing profiles of faecal samples and proteomic profiles of serum samples) from 40 UC patients at a single inflammatory bowel disease centre, as well as various clinical, endoscopic and histologic measures of disease activity. A validation cohort of 210 samples (73 UC, 117 Crohn's disease, 20 healthy controls) was collected and analysed separately and independently. Data integration across both cohorts showed that a subset of the clinically active UC patients had an overabundance of proteases that originated from the bacterium Bacteroides vulgatus. To test whether B. vulgatus proteases contribute to UC disease activity, we first profiled B. vulgatus proteases found in patients and bacterial cultures. Use of a broad-spectrum protease inhibitor improved B. vulgatus-induced barrier dysfunction in vitro, and prevented colitis in B. vulgatus monocolonized, IL10-deficient mice. Furthermore, transplantation of faeces from UC patients with a high abundance of B. vulgatus proteases into germfree mice induced colitis dependent on protease activity. These results, stemming from a multi-omics approach, improve understanding of functional microbiota alterations that drive UC and provide a resource for identifying other pathways that could be inhibited as a strategy to treat this disease.}, }
@article {pmid35086768, year = {2022}, author = {Servetas, SL and Daschner, PJ and Guyard, C and Thomas, V and Affagard, H and Sergaki, C and Sokol, H and Wargo, JA and Wu, GD and Sabot, P}, title = {Evolution of FMT - From early clinical to standardized treatments.}, journal = {Biologicals : journal of the International Association of Biological Standardization}, volume = {76}, number = {}, pages = {31-35}, doi = {10.1016/j.biologicals.2022.01.004}, pmid = {35086768}, issn = {1095-8320}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) is widely reported to be an effective treatment against recurrent Clostridioides difficile infections. Recent clinical studies support the therapeutic use of FMT for several other pathologies including inflammatory bowel disease, several types of cancer, and other functional or metabolic disorders. Initial guidelines are now available to overcome some of the technical and logistical issues for establishing a non-standardized treatment into clinical practice with proper safety and governance. To aid the improvement of guidance and standardization requirements for FMT, the International Alliance for Biological Standardization (IABS) and the BIOASTER Microbiology Technology Institute hosted a joint online workshop in May of 2021. The goal of the webinar was to provide a multi-disciplinary perspective of the ongoing efforts to develop FMT guidelines including technical, regulatory, and standardization requirements. Recognized experts gave insights into state-of-the art approaches and standards developed by international organizations and institutions.}, }
@article {pmid35084969, year = {2022}, author = {Servick, K}, title = {Alternatives to fecal transplants near approval.}, journal = {Science (New York, N.Y.)}, volume = {375}, number = {6579}, pages = {368-369}, doi = {10.1126/science.ada0539}, pmid = {35084969}, issn = {1095-9203}, mesh = {Capsules ; Clinical Trials, Phase III as Topic ; *Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Drug Approval ; *Fecal Microbiota Transplantation/adverse effects ; Feces/*microbiology ; *Firmicutes ; *Gastrointestinal Microbiome ; Humans ; Microbial Interactions ; *Spores, Bacterial ; United States ; United States Food and Drug Administration ; }, abstract = {[Figure: see text].}, }
@article {pmid35084496, year = {2022}, author = {Stapleton, TE and Kohl, KD and Dearing, MD}, title = {Plant secondary compound- and antibiotic-induced community disturbances improve the establishment of foreign gut microbiota.}, journal = {FEMS microbiology ecology}, volume = {98}, number = {1}, pages = {}, doi = {10.1093/femsec/fiac005}, pmid = {35084496}, issn = {1574-6941}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Fecal transplants are a powerful tool for manipulating the gut microbial community, but how these non-native communities establish in the presence of an intact host gut microbiome is poorly understood. We explored the microbiome of desert woodrats (Neotoma lepida) to determine whether disrupting existing microbial communities using plant secondary compounds (PSCs) or antibiotics increases the establishment of foreign microbes. We administered two fecal transplants between natural populations of adult woodrats that harbor distinct gut microbiota and have different natural dietary exposure to PSCs. First, we administered fecal transplants to recipients given creosote resin, a toxin found in the natural diet of our "donor" population, and compared the gut microbial communities to animals given fecal transplants and control diet using 16S rRNA gene sequencing. Second, we disrupted the gut microbial community of the same recipients with an antibiotic prior to fecal transplants. We found that gut microbial communities of woodrats disrupted with PSCs or antibiotics resembled that of donors more closely than control groups. PSC treatment also enriched microbes associated with metabolizing dietary toxins in transplant recipients. These results demonstrate that microbial community disturbances by PSCs or antibiotics are sufficient to facilitate establishment of foreign microbes in animals with intact microbiomes.}, }
@article {pmid35083238, year = {2021}, author = {Ding, L and He, C and Li, X and Huang, X and Lei, Y and Ke, H and Chen, H and Yang, Q and Cai, Y and Liao, Y and He, W and Xia, L and Xiong, H and Lu, N and Zhu, Y}, title = {Efficacy and Safety of Faecal Microbiota Transplantation for Acute Pancreatitis: A Randomised, Controlled Study.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {772454}, pmid = {35083238}, issn = {2296-858X}, abstract = {Aims: We investigated whether faecal microbiota transplantation (FMT) decreases intra-abdominal pressure (IAP) and improves gastrointestinal (GI) dysfunction and infectious complications in acute pancreatitis (AP). Methods: In this first randomised, single-blind, parallel-group, controlled study, we recruited and enrolled consecutive patients with AP complicated with GI dysfunction. Eligible participants were randomly assigned to receive faecal transplant (n = 30) or normal saline (n = 30) via a nasoduodenal tube once and then again 2 days later. The primary endpoint was the rate of IAP decline; secondary endpoints were GI function, infectious complications, organ failure, hospital stay and mortality. Analyses were based on intention to treat. Results: We enrolled 60 participants and randomly assigned them to the FMT (n = 30) or control (n = 30) group. Baseline characteristics and disease severity were similar for both groups. IAP decreased significantly 1 week after intervention in both groups, with no difference in the IAP decline rate between FMT and Control group [0.1 (-0.6, 0.5) vs. 0.2 (-0.2, 0.6); P = 0.27]. Normal gastrointestinal failure (GIF) scores were achieved in 12 (40%) patients in the FMT group and 14 (47%) in the control group, with no significant difference (P = 0.60). However, D-lactate was significantly elevated in the FMT group compared to the control group, as calculated by the rate of decline [-0.3 (-3.7, 0.8) vs. 0.4 (-1.1, 0.9); P = 0.01]. Infectious complications occurred in 15 (50%) and 16 (53.33%) patients in the FMT and control groups, respectively (P = 0.80). However, interleukin-6 (IL-6) was significantly elevated in the FMT group compared to the control group, as calculated by the rate of decline [0.4 (-3.6, 0.9) vs. 0.8 (-1.7, 1.0); P = 0.03]. One participant experienced transient nausea immediately after FMT, but no serious adverse events were attributed to FMT. Conclusion: FMT had no obvious effect on IAP and infectious complications in AP patients, though GI barrier indictors might be adversely affected. Further multi-centre studies are needed to confirm our findings. The study was registered at https://clinicaltrials.gov (NCT02318134).}, }
@article {pmid35081663, year = {2022}, author = {Shehata, E and Parker, A and Suzuki, T and Swann, JR and Suez, J and Kroon, PA and Day-Walsh, P}, title = {Microbiomes in physiology: insights into 21st-century global medical challenges.}, journal = {Experimental physiology}, volume = {107}, number = {4}, pages = {257-264}, pmid = {35081663}, issn = {1469-445X}, support = {/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; BB/R012512/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10343/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10346/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10347/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10355/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {NEW FINDINGS: What is the topic of this review? The role of the gut microbiome in physiology and how it can be targeted as an effective strategy against two of the most important global medical challenges of our time, namely, metabolic diseases and antibacterial resistance. What advances does it highlight? The critical roles of the microbiome in regulating host physiology and how microbiome analysis is useful for disease stratification to enable informed clinical decisions and develop interventions such as faecal microbiota transplantation, prebiotics and probiotics. Also, the limitations of microbiome modulation, including the potential for probiotics to enhance antimicrobial resistance gene reservoirs, and that currently a 'healthy microbiome' that can be used as a biobank for transplantation is yet to be defined.<br><br>ABSTRACT: The human gut microbiome is a key factor in the development of metabolic diseases and antimicrobial resistance, which are among the greatest global medical challenges of the 21st century. A recent symposium aimed to highlight state-of-the-art evidence for the role of the gut microbiome in physiology, from childhood to adulthood, and the impact this has on global disease outcomes, ageing and antimicrobial resistance. Although the gut microbiome is established early in life, over time the microbiome and its components including metabolites can become perturbed due to changes such as dietary habits, use of antibiotics and age. As gut microbial metabolites, including short-chain fatty acids, secondary bile acids and trimethylamine-N-oxide, can interact with host receptors including G protein-coupled receptors and can alter host metabolic fluxes, they can significantly affect physiological homoeostasis leading to metabolic diseases. These metabolites can be used to stratify disease phenotypes such as irritable bowel syndrome and adverse events after heart failure and allow informed decisions on clinical management and treatment. While strategies such as use of probiotics, prebiotics and faecal microbiota transplantation have been proposed as interventions to treat and prevent metabolic diseases and antimicrobial resistance, caution must be exercised, first due to the potential of probiotics to enhance antimicrobial resistance gene reservoirs, and second, a 'healthy gut microbiome' that can be used as a biobank for transplantation is yet to be defined. We highlight that sampling other parts of the gastrointestinal tract may produce more representative data than the faecal microbiome alone.}, }
@article {pmid35077579, year = {2022}, author = {Gu, Z and Xiong, Q and Wang, L and Wang, L and Li, F and Hou, C and Dou, L and Zhu, B and Liu, D}, title = {The impact of intestinal microbiota in antithymocyte globulin-based myeloablative allogeneic hematopoietic cell transplantation.}, journal = {Cancer}, volume = {128}, number = {7}, pages = {1402-1410}, doi = {10.1002/cncr.34091}, pmid = {35077579}, issn = {1097-0142}, support = {82070178//National Natural Science Foundation of China/ ; ZH19003//Military Translational Medicine Fund of Chinese PLA General Hospital/ ; }, mesh = {Antilymphocyte Serum/therapeutic use ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/etiology/prevention &amp; control ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Transplantation Conditioning/adverse effects ; Transplantation, Homologous/adverse effects ; }, abstract = {BACKGROUND: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HCT) has been reported in platforms with T-cell depletion or postcyclophosphamide-based graft-vs-host disease (GVHD) prophylaxis regimens. It is still unclear whether it is the same in platforms of antithymocyte globulin (ATG)-based myeloablative allo-HCT.<br><br>METHODS: A total of 603 fecal specimens from 100 consecutive patients receiving allo-HCT were collected between December 2018 and July 2020. Fetal samples were profiled with next-generation sequencing of bacterial 16S ribosomal RNA (rRNA) genes.<br><br>RESULTS: The diversity decreased to the lowest level at approximately day 12 after allo-HCT and then increased over time. According to the diversity of 314 samples that were collected from 86 patients during the engraftment period, patients were grouped into the low- and high-diversity groups. Two-year overall survival in the high-diversity group was significantly longer than that in the low-diversity group (83.7% vs 60.6%, P&#xa0;=&#xa0;.026). Further analysis revealed that worse outcomes for patients with low diversity were associated with increased risk of worse outcomes for patients with low diversity (adjusted hazard ratio, 4.95; P&#xa0;=&#xa0;.046). Its association with relapse and GVHD was not found. Compositional analysis of fecal microbiota revealed that the abundance of bacteroides decreased greatly during allo-HCT, whereas that of Enterococcus, Klebsiella, and Escherichia was found to be increased.<br><br>CONCLUSIONS: This study indicates that gut dysbiosis in platforms of ATG-based myeloablative allo-HCT featured loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period was an independent predictor of longer survival.<br><br>LAY SUMMARY: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HCT) is reported in platforms with T-cell depletion or postcyclophosphamide-based graft-vs-host disease (GVHD) prophylaxis regimens. It is still unclear whether it is the same pattern in platforms of antithymocyte globulin (ATG)-based T-cell repletion myeloablative allo-HCT. Our study indicated that gut dysbiosis in platforms of ATG-based myeloablative allo-HCT also features loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period is an independent predictor of longer survival.}, }
@article {pmid35077172, year = {2022}, author = {Wang, T and Shi, C and Wang, S and Zhang, Y and Wang, S and Ismael, M and Zhang, J and Wang, X and Lü, X}, title = {Protective Effects of Companilactobacillus crustorum MN047 against Dextran Sulfate Sodium-Induced Ulcerative Colitis: A Fecal Microbiota Transplantation Study.}, journal = {Journal of agricultural and food chemistry}, volume = {70}, number = {5}, pages = {1547-1561}, doi = {10.1021/acs.jafc.1c07316}, pmid = {35077172}, issn = {1520-5118}, mesh = {*Colitis ; *Colitis, Ulcerative/genetics/therapy ; Dextran Sulfate ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Gut microbiota dysbiosis could aggravate the development of ulcerative colitis (UC). Companilactobacillus crustorum MN047 (CCMN) is a potential gut microbiota-regulating probiotic that could produce multiple novel bacteriocins. In this study, fecal microbiota transplantation (FMT) was used to verify whether CCMN could alleviate dextran sulfate sodium-induced UC by regulating gut microbiota. Results showed that both CCMN and FMT ameliorated the symptoms of UC, including attenuating the increased disease activity index, shortened colon length, gut barrier damage, and inflammation. Briefly, CCMN and FMT upregulated the expressions of MUCs and tight junctions, downregulated the expressions of proinflammatory cytokines and chemokines, increased fecal short-chain fatty acids, and lowered serum lipopolysaccharides, which were associated with the regulation of gut microbiota (e.g., increased Akkermansia, Blautia, and Ruminococcus levels). These results demonstrated that CCMN could ameliorate UC by modulating gut microbiota and inhibiting the TLR4/NF-κB pathway. Therefore, CCMN could be considered as a potential probiotic supplement for ameliorating UC.}, }
@article {pmid35076517, year = {2022}, author = {Merrick, B and Tamilarasan, AG and Luber, R and Yong, PFK and Cheent, K and Irving, PM and Meda, M and Goldenberg, SD}, title = {Recurrent Campylobacter jejuni Infection in an Immunodeficient Patient Treated with Repeated Faecal Microbiota Transplant (FMT)-A Case Report.}, journal = {Infectious disease reports}, volume = {14}, number = {1}, pages = {56-62}, pmid = {35076517}, issn = {2036-7430}, abstract = {There is limited evidence to guide successful treatment of recurrent Campylobacter infection in patients with common variable immunodeficiency (CVID) already managed on regular immunoglobulin therapy. The role of faecal microbiota transplant (FMT) is uncertain. We report a case of recurrent Campylobacter jejuni infection in a patient with CVID treated with repeated FMT with 18 months of symptom resolution prior to relapse.}, }
@article {pmid35076278, year = {2022}, author = {Lozada-Fernández, VV and deLeon, O and Kellogg, SL and Saravia, FL and Hadiono, MA and Atkinson, SN and Grobe, JL and Kirby, JR}, title = {Nicotinamide Riboside-Conditioned Microbiota Deflects High-Fat Diet-Induced Weight Gain in Mice.}, journal = {mSystems}, volume = {7}, number = {1}, pages = {e0023021}, pmid = {35076278}, issn = {2379-5077}, support = {R01 HL134850/HL/NHLBI NIH HHS/United States ; P01 HL084207/HL/NHLBI NIH HHS/United States ; R01 AI108255/AI/NIAID NIH HHS/United States ; T32 GM080202/GM/NIGMS NIH HHS/United States ; }, mesh = {Male ; Humans ; Animals ; Mice ; Diet, High-Fat ; NAD/adverse effects ; *Diabetes Mellitus, Type 2 ; Mice, Inbred C57BL ; Weight Gain ; Obesity/chemically induced ; *Gastrointestinal Microbiome ; Vitamins/adverse effects ; }, abstract = {The gut microbiome plays an essential role in host energy homeostasis and influences the development of obesity and related conditions. Studies demonstrate that nicotinamide riboside (NR) supplementation for diet-induced obesity (DIO) reduces weight gain and increases energy expenditure in mice. NR is a vitamin B3 derivative and an NAD[+] precursor with potential for treating human diseases arising from mitochondrial degeneration, including obesity and type 2 diabetes. Gut bacteria produce vitamin B3 in the colon and are capable of salvaging and metabolizing vitamin B3 and its derivatives. However, it is unknown how dietary supplementation of NR alters the microbiome and if those alterations contribute to deflection of weight gain. In this study, we fed C57BL/6J male mice a high-fat diet (HFD) supplemented with or without NR and performed a fecal material transfer (FMT) to establish a link between NR-conditioned microbiota and NR-induced deflection of weight gain. FMT from NR-treated donors to naive mice fed a HFD was sufficient to deflect weight gain by increasing energy expenditure. We also investigated the effects of NR on the microbiome by using metagenomics sequencing. We found that NR-treated mice displayed an altered gut microbial composition relative to controls and that fecal transplant resulted in a distinct functional metabolic profile characterized by enrichment of butyrate-producing Firmicutes. NR-treated donors and subsequent FMT recipients share a similar enrichment of metagenomic biomarkers relative to controls. These findings suggest that microbial factors contribute to the beneficial effects of dietary NR supplementation, which may be useful to enhance the therapeutic effects of NR. IMPORTANCE With obesity and type 2 diabetes (T2D) at epidemic levels, we need to understand the complex nature of these diseases to design better therapeutics. The underlying causes of both obesity and T2D are complex, but both are thought to develop, in part, based on contributions from the gut microbiota. Nicotinamide riboside is a gut-derived vitamin B3 derivative and NAD[+] precursor which has the potential to treat and prevent metabolic disorders by ameliorating mitochondrial dysfunction. Understanding how NR affects the gut microbiome and whether NR-conditioned microbiota contributes to weight loss in the host would (i) improve diagnosis and treatments for obesity and other metabolic pathologies, (ii) tailor treatments to satisfy the needs of each individual moving toward the future of precision medicine, and (iii) benefit other scientific fields that currently investigate the effects of NR in other disease pathologies.}, }
@article {pmid35076274, year = {2022}, author = {Sauve, AA}, title = {Metabolic Disease, NAD Metabolism, Nicotinamide Riboside, and the Gut Microbiome: Connecting the Dots from the Gut to Physiology.}, journal = {mSystems}, volume = {7}, number = {1}, pages = {e0122321}, pmid = {35076274}, issn = {2379-5077}, support = {P30 DK020541/DK/NIDDK NIH HHS/United States ; R01 AG066192/AG/NIA NIH HHS/United States ; R01 ES027488/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; NAD/metabolism ; *Gastrointestinal Microbiome ; Diet, High-Fat ; Nicotinamide Mononucleotide/metabolism ; Weight Gain ; *Microbiota ; *Metabolic Diseases ; }, abstract = {The effort to use nutrients as interventions to treat human disease has been important to medicine. A current example in this vein pertains to NAD[+] boosters, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which are in many clinical trials in a variety of disease conditions. Independent laboratories have shown that ingested NR (or NMN) has mitigating effects on metabolic syndrome in mice. V. V. Lozada-Fernández, O. deLeon, S. L. Kellogg, F. L. Saravia, et al. (mSystems 7:e00230-21, 2022, https://doi.org/10.1128/mSystems.00230-21) show that NR shifts gut microbiome contents and that the transplantation of an NR-conditioned microbiome by fecal transfer reproduces some effects of NR in mice on a high-fat diet. The involvement of the gut microbiome as a factor in NR effects is linked to changes to the gut microbiome and its activity to transform NR and downstream catabolites. This commentary draws attention to these findings and focuses on some puzzling aspects of NAD[+] boosters, exploring the still murky interactions between NAD[+] metabolism, energy homeostasis, and the gut microbiome.}, }
@article {pmid35074739, year = {2022}, author = {Xu, J and Wang, M and Liu, Q and Lin, X and Pu, K and He, Z}, title = {Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice.}, journal = {Ecotoxicology and environmental safety}, volume = {231}, number = {}, pages = {113224}, doi = {10.1016/j.ecoenv.2022.113224}, pmid = {35074739}, issn = {1090-2414}, mesh = {Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Nitrites/toxicity ; }, abstract = {Growing evidence indicates that exposure to high levels of nitrite for a prolonged time has adverse health effects. Although gut microbiota is responsible for the transformation of nitrite in the gut, the evidence concerning whether gut microbiota mediates the toxicity of nitrite is still lacking. The present study addressed the long-term effects of dietary nitrite on male C57BL/6 mice and employed fecal microbiota transplantation (FMT) to reveal whether gut microbiota mediated the effects of nitrite. Furthermore, the effect of azoxymethane (AOM) on gut microbiota was detected for mice drinking normal or nitrite-containing water. High nitrite had toxic effects on C57BL/6 mice. Meanwhile, high nitrite induced skin lesions in mice, accompanied with increased serum ALT, colon IL-6, TNF-α, and MDA levels, together with decreased serum Cr, colon sIgA, and T-AOC levels. After fecal microbiota was transplanted into the normal mice, the nitrite-regulated gut microbiota could also induce skin lesions, coupled with reduced serum Cr, and increased colon MDA. The high dose of nitrite caused the upregulations of Alistipes, Prevotella, and Ruminococcus, which could be transplanted into normal mice through FMT. Inversely, gut microbiota from normal mice reduced the effects of nitrite on serum ALT and Cr, together with colon sIgA and MDA. Gut microbiota from normal mice could also upregulate metabolic genes and downregulate stress genes in the nitrite-treated mice. It might due to the upregulation of Akkermansia and Parabacteroides caused by FMT from normal water-treated mice to nitrite-treated mice. In addition, AOM exhibited to be more toxic to the colon in the nitrite-treated mice in comparison with normal water-treated mice, and it might be due to the expression of Hspa1a and Hspa1b in the colon. Interestingly, gut microbiota was more influenced by AOM in the normal water-treated mice than the nitrite-treated mice. Overall, these data demonstrated that gut microbiota mediated the toxicity of a high concentration of dietary nitrite.}, }
@article {pmid35074372, year = {2022}, author = {Yan, J and Chen, Q and Tian, L and Li, K and Lai, W and Bian, L and Han, J and Jia, R and Liu, X and Xi, Z}, title = {Intestinal toxicity of micro- and nano-particles of foodborne titanium dioxide in juvenile mice: Disorders of gut microbiota-host co-metabolites and intestinal barrier damage.}, journal = {The Science of the total environment}, volume = {821}, number = {}, pages = {153279}, doi = {10.1016/j.scitotenv.2022.153279}, pmid = {35074372}, issn = {1879-1026}, mesh = {Animals ; *Gastrointestinal Microbiome ; Intestines ; Mice ; *Nanoparticles/toxicity ; Titanium/toxicity ; }, abstract = {The wide use of TiO2 particles in food and the high exposure risk to children have prompted research into the health risks of TiO2. We used the microbiome and targeted metabolomics to explore the potential mechanism of intestinal toxicity of foodborne TiO2 micro-/nanoparticles after oral exposure for 28 days in juvenile mice. Results showed that the gut microbiota-including the abundance of Bacteroides, Bifidobacterium, Lactobacillus, and Prevotella-changed dynamically during exposure. The organic inflammatory response was activated, and lipopolysaccharide levels increased. Intestinal toxicity manifested as increased mucosal permeability, impaired intestinal barrier, immune damage, and pathological changes. The expression of antimicrobial peptides, occludin, and ZO-1 significantly reduced, while that of JNK2 and Src/pSrc increased. Compared with micro-TiO2 particles, the nano-TiO2 particles had strong toxicity. Fecal microbiota transplant confirmed the key role of gut microbiota in intestinal toxicity. The levels of gut microbiota-host co-metabolites, including pyroglutamic acid, L-glutamic acid, phenylacetic acid, and 3-hydroxyphenylacetic acid, changed significantly. Significant changes were observed in the glutathione and propanoate metabolic pathways. There was a significant correlation between the changes in gut microbiota, metabolites, and intestinal cytokine levels. These, together with the intestinal barrier damage signaling pathway, constitute the network mechanism of the intestinal toxicity of TiO2 particles.}, }
@article {pmid35073073, year = {2022}, author = {Liu, Y and Huang, W and Zhu, Y and Zhao, T and Xiao, F and Wang, Y and Lu, B}, title = {Acteoside, the Main Bioactive Compound in Osmanthus fragrans Flowers, Palliates Experimental Colitis in Mice by Regulating the Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {70}, number = {4}, pages = {1148-1162}, doi = {10.1021/acs.jafc.1c07583}, pmid = {35073073}, issn = {1520-5118}, mesh = {Animals ; *Colitis/chemically induced/drug therapy ; Colon ; Dextran Sulfate ; Disease Models, Animal ; Flowers ; *Gastrointestinal Microbiome ; Glucosides ; Mice ; Mice, Inbred C57BL ; Phenols ; }, abstract = {The present study investigated the effects of Osmanthus fragrans flowers and acteoside on murine colitis and the underlying mechanisms. The O. fragrans flower extract (OFE) and acteoside were administrated to chemically induced colitic mice. The results showed that OFE or acteoside ameliorates intestinal inflammation, oxidative stress, and activation of nuclear factor-κB (NF-κB) in colitic mice. The dysbiosis of the gut microbiome in colitic mice was also partly restored by OFE or acteoside, which was characterized by the alteration of the gut microbiome structure and the enrichment of beneficial bacteria (Akkermansia muciniphila and Bacteroides thetaiotaomicron). Dextran sulfate sodium (DSS)-induced gut metabolome dysfunctions (e.g., sphingosine metabolism and amino acids metabolism) in colitic mice were also partly restored by OFE and acteoside. A fecal microbiota (FM) transplantation study suggested that, compared with the FM from the normal diet-dosed donor mice, the FM from the OFE- or acteoside-dosed donor mice significantly suppressed colitic symptoms.}, }
@article {pmid35069989, year = {2021}, author = {Zhao, LN and Ma, SW and Xiao, J and Yang, LJ and Xu, SX and Zhao, L}, title = {Bone marrow mesenchymal stem cell therapy regulates gut microbiota to improve post-stroke neurological function recovery in rats.}, journal = {World journal of stem cells}, volume = {13}, number = {12}, pages = {1905-1917}, pmid = {35069989}, issn = {1948-0210}, abstract = {BACKGROUND: As a cellular mode of therapy, bone marrow mesenchymal stem cells (BMSCs) are used to treat stroke. However, their mechanisms in stroke treatment have not been established. Recent evidence suggests that regulation of dysregulated gut flora after stroke affects stroke outcomes.<br><br>AIM: To investigate the effects of BMSCs on gut microbiota after ischemic stroke.<br><br>METHODS: A total of 30 Sprague-Dawley rats were randomly divided into three groups, including sham operation control group, transient middle cerebral artery occlusion (MCAO) group, and MCAO with BMSC treatment group. The modified Neurological Severity Score (mNSS), beam walking test, and Morris water maze test were used to evaluate neurological function recovery after BMSC transplantation. Nissl staining was performed to elucidate on the pathology of nerve cells in the hippocampus. Feces from each group of rats were collected and analyzed by 16s rDNA sequencing.<br><br>RESULTS: BMSC transplantation significantly reduced mNSS (P < 0.01). Rats performed better in the beam walking test in the BMSC group than in the MCAO group (P < 0.01). The Morris water maze test revealed that the BMSC treatment group exhibited a significant improvement in learning and memory. Nissl staining for neuronal damage assessment after stroke showed that in the BMSC group, cells were orderly arranged with significantly reduced necrosis. Moreover, BMSCs regulated microbial structure composition. In rats treated with BMSCs, the abundance of potential short-chain fatty acid producing bacteria and Lactobacillus was increased.<br><br>CONCLUSION: BMSC transplantation is a potential therapeutic option for ischemic stroke, and it promotes neurological functions by regulating gut microbiota dysbiosis.}, }
@article {pmid35069488, year = {2021}, author = {George, S and Aguilera, X and Gallardo, P and Farfán, M and Lucero, Y and Torres, JP and Vidal, R and O'Ryan, M}, title = {Bacterial Gut Microbiota and Infections During Early Childhood.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {793050}, pmid = {35069488}, issn = {1664-302X}, abstract = {Gut microbiota composition during the first years of life is variable, dynamic and influenced by both prenatal and postnatal factors, such as maternal antibiotics administered during labor, delivery mode, maternal diet, breastfeeding, and/or antibiotic consumption during infancy. Furthermore, the microbiota displays bidirectional interactions with infectious agents, either through direct microbiota-microorganism interactions or indirectly through various stimuli of the host immune system. Here we review these interactions during childhood until 5 years of life, focusing on bacterial microbiota, the most common gastrointestinal and respiratory infections and two well characterized gastrointestinal diseases related to dysbiosis (necrotizing enterocolitis and Clostridioides difficile infection). To date, most peer-reviewed studies on the bacterial microbiota in childhood have been cross-sectional and have reported patterns of gut dysbiosis during infections as compared to healthy controls; prospective studies suggest that most children progressively return to a "healthy microbiota status" following infection. Animal models and/or studies focusing on specific preventive and therapeutic interventions, such as probiotic administration and fecal transplantation, support the role of the bacterial gut microbiota in modulating both enteric and respiratory infections. A more in depth understanding of the mechanisms involved in the establishment and maintenance of the early bacterial microbiota, focusing on specific components of the microbiota-immunity-infectious agent axis is necessary in order to better define potential preventive or therapeutic tools against significant infections in children.}, }
@article {pmid35068600, year = {2022}, author = {Zhu, J and Su, J}, title = {Alterations of the Gut Microbiome in Recurrent Malignant Gliomas Patients Received Bevacizumab and Temozolomide Combination Treatment and Temozolomide Monotherapy.}, journal = {Indian journal of microbiology}, volume = {62}, number = {1}, pages = {23-31}, pmid = {35068600}, issn = {0046-8991}, abstract = {UNLABELLED: This case-control study explored compositions of gut microbiome in recurrent malignant gliomas patients who had received bevacizumab and Temozolomide combination treatment and Temozolomide monotherapy. We investigated gut microbiota communities in feces of 29 recurrent malignant gliomas patients received combination treatment with bevacizumab and Temozolomide (Group 1) and monotherapy with Temozolomide alone (Group 2). We took advantage of the high-throughput Illumina Miseq sequencing technology by targeting the third and fourth hypervariable (V3-V4) regions of the 16S ribosomal RNA (rRNA) gene. We found that the structures and richness of the fecal microbiota in Group 1 were different from Group 2 with LEfSe analysis. The fecal microbiota in both Group 1 and Group 2 were mainly composed by Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. However, Group 1 patients had higher relative abundance of Firmicutes, Bacteroidetes, Actinobacteria and lower relative abundance of Bacteroidetes and Cyanobacteria in their fecal microbiota than that in Group 2 patients. To evaluate bevacizumab involved post-treatment state of the fecal microbiota profile, we used random forest predictive model and ensembled decision trees with an AUC of 0.54. This study confirmed that the gut microbiota was different in recurrent malignant gliomas patients received the combination therapy of bevacizumab and Temozolomide compared with Temozolomide monotherapy. Our discover can help better understand the influence of bevacizumab related treatment on recurrent malignant gliomas patients. Therefore, this finding may also support the potentially therapeutic options for recurrent malignant gliomas patients such as fecal microbiota transplant.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-021-00962-2.}, }
@article {pmid35068020, year = {2022}, author = {Feng, Y and Zhang, D and Zhao, Y and Duan, T and Sun, H and Ren, L and Ren, X and Lu, G and Liu, Y and Zhang, Z and Li, Y and Li, H and Jia, A and He, S}, title = {Effect of intestinal microbiota transplantation on cerebral ischemia reperfusion injury in aged mice via inhibition of IL-17.}, journal = {Neurogastroenterology and motility}, volume = {34}, number = {7}, pages = {e14313}, doi = {10.1111/nmo.14313}, pmid = {35068020}, issn = {1365-2982}, mesh = {Animals ; Fecal Microbiota Transplantation ; Infarction, Middle Cerebral Artery/therapy ; Interleukin-17 ; Mice ; *Neuroprotective Agents/pharmacology ; *Reperfusion Injury/therapy ; }, abstract = {OBJECTIVES: This study investigates the effects and mechanisms of intestinal microbiota transplantation on cerebral ischemia reperfusion injury in aged mice.<br><br>METHODS: We constructed a middle cerebral artery occlusion model after fecal microbiota transplantation from young C57 mice to aged C57 mice for 30 consecutive days via enema. The neurological deficit score, cerebral infarction volume, fecal flora composition, and IL-17 levels in the colon, brain, and serum were evaluated in young mice, aged mice, and aged mice that received fecal microbiota transplantation. Moreover, we administered rIL-17A through caudal vein injection to verify its effect on cerebral ischemia reperfusion injury in aged mice.<br><br>RESULTS: We find that aged mice exhibited larger cerebral infarction volume and more severe neurological deficit than young mice after middle cerebral artery occlusion. Bacteroidetes increased and firmicutes decreased significantly in the feces of aged mice after microbiota transplantation. Furthermore, the transplanted mice showed improved neurological function and reduced infarction volume after middle cerebral artery occlusion compared with the control aged mice. We also find that the neuroprotective effect of the microbiota transplantation was reversed by pre-treatment of rIL-17A.<br><br>CONCLUSION: In summary, intestinal microbiota transplantation can alleviate cerebral ischemia reperfusion injury in aged mice by restoring their microbiota environment and inhibiting IL-17 in the gut, serum, and brain tissue.}, }
@article {pmid35064986, year = {2022}, author = {Lengliz, S and Cheriet, S and Raddaoui, A and Klibi, N and Ben Chehida, N and Najar, T and Abbassi, MS}, title = {Species distribution and genes encoding antimicrobial resistance in enterococcus spp. isolates from rabbits residing in diverse ecosystems: A new reservoir of linezolid and vancomycin resistance.}, journal = {Journal of applied microbiology}, volume = {132}, number = {4}, pages = {2760-2772}, doi = {10.1111/jam.15461}, pmid = {35064986}, issn = {1365-2672}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Drug Resistance, Bacterial/genetics ; Ecosystem ; *Enterococcus ; Linezolid/pharmacology ; Microbial Sensitivity Tests ; Rabbits ; *Vancomycin Resistance ; }, abstract = {AIMS: Worldwide, studies regarding antimicrobial resistance in rabbits are scarce. In addition, it seems that rearing conditions have important impact on emergence and spread of antimicrobial-resistant bacteria. Thus, the authors sought to (1) assess the role of rabbits residing across diverse ecosystems as potential reservoirs of antimicrobial-resistant enterococci and (2) investigate the genetic background of detected resistances.<br><br>METHODS AND RESULTS: Faecal samples from 60 healthy farmed rabbits (one farm), 35 laboratory rabbits and 31 wild rabbits were analysed. Overall, 97 enterococci isolates were accumulated, as follows: 44 E. faecium, 37 E. faecalis, 7 E. gallinarum, 5 E. durans and 4 E. avium. E. faecalis isolates were statistically associated with farm rabbits and wild rabbits (p&#xa0;<&#xa0;0.05). High rates of resistance were observed for tetracycline (60.8%; tetM [n&#xa0;=&#xa0;48; 81.3%], tetO [n&#xa0;=&#xa0;7; 11.8%] and tetL [n&#xa0;=&#xa0;1; 1.7%]), erythromycin (43.3%; msr(A) [n&#xa0;=&#xa0;14; 33.3%] and ermB [n&#xa0;=&#xa0;13; 31%]), ampicillin (29.9%), streptomycin (26.8%; ant(6)-Ia [n&#xa0;=&#xa0;3, 11.5%]) and vancomycin (21.6%; vanA [one E. faecium&#xa0;+&#xa0;one E. faecalis; 9.5%]). Low frequencies of resistance were observed for teicoplanin (9.2%), linezolid (8.2%), ciprofloxacin (7.2%) and gentamicin (1%; aac(6')-Ie-aph(2&#x2033;)-Ia). Resistance to ampicillin and vancomycin was associated with laboratory rabbits (p&#xa0;<&#xa0;0.05). Int-Tn (Tn916/1545) was detected in 27 (27.8%) isolates, of which 10 isolates co-harboured tetM and ermB genes, while 16 comprised tetM.<br><br>CONCLUSION: Findings indicate that clinically relevant enterococci species isolated from rabbits are frequently resistant to antimicrobials and harbour a range of genes associated with the Tn916/1545 family.<br><br>This study highlights the high rates of antimicrobial-resistant enterococci from rabbits and the occurrence of both vancomycin- and linezolid-resistant isolates, potentially representing a very serious threat to human and animal health.}, }
@article {pmid35064189, year = {2022}, author = {Su, L and Hong, Z and Zhou, T and Jian, Y and Xu, M and Zhang, X and Zhu, X and Wang, J}, title = {Health improvements of type 2 diabetic patients through diet and diet plus fecal microbiota transplantation.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {1152}, pmid = {35064189}, issn = {2045-2322}, mesh = {Adult ; Aged ; Blood Glucose/analysis ; Diabetes Mellitus, Type 2/blood/diagnosis/microbiology/*therapy ; Dysbiosis/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Prebiotics/*administration &amp; dosage ; Probiotics/*administration &amp; dosage ; Treatment Outcome ; Whole Grains ; }, abstract = {Type 2 diabetes (T2D) is a major public health problem, and gut microbiota dysbiosis has been implicated in the emergence of T2D in humans. Dietary interventions can indirectly influence the health status of patients with type 2 diabetes through their modulatory effects on the intestinal microbiota. In recent years, fecal microbiota transplantation is becoming familiar as a new medical treatment that can rapidly improve intestinal health. We conducted a 90-day controlled open-label trial to evaluate the health improvement ability of a specially designed diet, and the diet combined with fecal microbiota transplantation (FMT). According to our study, both diet and diet plus FMT treatments showed great potential in controlling blood glucose and blood pressure levels. Sequencing the V4 region of 16S rRNA gene on the Illumina MiniSeq platform revealed a shift of intestinal microbial community in T2D patients, and the changes were also observed in response to the treatments. FMT changed the gut microbiota more quickly than diet. Beneficial bacterium, such as Bifidobacterium, increased along the study and was negatively correlated with blood glucose, blood pressure, blood lipid and BMI. Sulfate-reducing bacteria (SRB), Bilophila and Desulfovibrio, decreased significantly after treatment, showed a positive correlation with blood glucose indices. Thus, the specially designed diet is beneficial to improve blood glucose control in diabetic patients, it also showed the potential to reverse dyslipidemia and dysarteriotony.}, }
@article {pmid35062949, year = {2022}, author = {Yi, M and Zheng, X and Niu, M and Zhu, S and Ge, H and Wu, K}, title = {Combination strategies with PD-1/PD-L1 blockade: current advances and future directions.}, journal = {Molecular cancer}, volume = {21}, number = {1}, pages = {28}, pmid = {35062949}, issn = {1476-4598}, mesh = {Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; B7-H1 Antigen/*antagonists &amp; inhibitors ; Biomarkers, Tumor ; Clinical Studies as Topic ; Combined Modality Therapy ; Disease Management ; Disease Susceptibility ; Humans ; Immune Checkpoint Inhibitors/administration &amp; dosage ; *Molecular Targeted Therapy ; Neoplasms/diagnosis/*drug therapy/etiology/mortality ; Prognosis ; Programmed Cell Death 1 Receptor/*antagonists &amp; inhibitors ; Treatment Outcome ; }, abstract = {Antibodies targeting programmed cell death protein-1 (PD-1) or its ligand PD-L1 rescue T cells from exhausted status and revive immune response against cancer cells. Based on the immense success in clinical trials, ten α-PD-1 (nivolumab, pembrolizumab, cemiplimab, sintilimab, camrelizumab, toripalimab, tislelizumab, zimberelimab, prolgolimab, and dostarlimab) and three α-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for various types of cancers. Nevertheless, the low response rate of α-PD-1/PD-L1 therapy remains to be resolved. For most cancer patients, PD-1/PD-L1 pathway is not the sole speed-limiting factor of antitumor immunity, and it is insufficient to motivate effective antitumor immune response by blocking PD-1/PD-L1 axis. It has been validated that some combination therapies, including α-PD-1/PD-L1 plus chemotherapy, radiotherapy, angiogenesis inhibitors, targeted therapy, other immune checkpoint inhibitors, agonists of the co-stimulatory molecule, stimulator of interferon genes agonists, fecal microbiota transplantation, epigenetic modulators, or metabolic modulators, have superior antitumor efficacies and higher response rates. Moreover, bifunctional or bispecific antibodies containing α-PD-1/PD-L1 moiety also elicited more potent antitumor activity. These combination strategies simultaneously boost multiple processes in cancer-immunity cycle, remove immunosuppressive brakes, and orchestrate an immunosupportive tumor microenvironment. In this review, we summarized the synergistic antitumor efficacies and mechanisms of α-PD-1/PD-L1 in combination with other therapies. Moreover, we focused on the advances of α-PD-1/PD-L1-based immunomodulatory strategies in clinical studies. Given the heterogeneity across patients and cancer types, individualized combination selection could improve the effects of α-PD-1/PD-L1-based immunomodulatory strategies and relieve treatment resistance.}, }
@article {pmid35062066, year = {2022}, author = {Hueso, M and Griñán, R and Mallen, A and Navarro, E and Purqueras, E and Gomá, M and Sbraga, F and Blasco-Lucas, A and Revilla, G and Santos, D and Canyelles, M and Julve, J and Escolà-Gil, JC and Rotllan, N}, title = {MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {146}, number = {}, pages = {112596}, doi = {10.1016/j.biopha.2021.112596}, pmid = {35062066}, issn = {1950-6007}, mesh = {Animals ; Biological Transport ; Cholesterol, HDL/*genetics/metabolism ; Down-Regulation ; Humans ; Macrophages/metabolism ; Mice ; MicroRNAs/*metabolism ; Receptors, Scavenger/*metabolism ; }, abstract = {OBJECTIVE: To determine whether miR-125b regulates cholesterol efflux in vivo and in vitro through the regulation of scavenger receptor type B1 (SR-B1).<br><br>APPROACH AND RESULTS: We demonstrated that miR-125b is up-regulated in the human aortas of patients with CAD and is located in macrophages and vascular smooth muscle cells (VSMCs). We identified SCARB1 as a direct target of miR-125b by repressing the activity of the SCARB1 3'-untranslated region reporter construct. Moreover, the overexpression of miR-125b in both human and mouse macrophages as well as VSMCs was found to downregulated the expression of the SCARB1 and the SR-B1 protein levels, thereby impairing &#x3b1;-HDL-mediated macrophage cholesterol efflux in vitro. The in vivo reverse cholesterol transport (RCT) rate from non-cholesterol-loaded macrophages transfected with miR-125b to feces was also found to be decreased when compared with that of control mimic-transfected macrophages.<br><br>CONCLUSIONS: Together, these results provide evidence that miR-125b downregulates SCARB1 and SR-B1 in both human and mouse macrophages as well as VSMCs, thereby impairing macrophage cholesterol efflux in vitro and the whole macrophage-specific RCT pathway in vivo.}, }
@article {pmid35061893, year = {2022}, author = {Miltiadous, O and Waters, NR and Andrlová, H and Dai, A and Nguyen, CL and Burgos da Silva, M and Lindner, S and Slingerland, J and Giardina, P and Clurman, A and Armijo, GK and Gomes, ALC and Lakkaraja, M and Maslak, P and Scordo, M and Shouval, R and Staffas, A and O'Reilly, R and Taur, Y and Prockop, S and Boelens, JJ and Giralt, S and Perales, MA and Devlin, SM and Peled, JU and Markey, KA and van den Brink, MRM}, title = {Early intestinal microbial features are associated with CD4 T-cell recovery after allogeneic hematopoietic transplant.}, journal = {Blood}, volume = {139}, number = {18}, pages = {2758-2769}, pmid = {35061893}, issn = {1528-0020}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; }, mesh = {CD4-Positive T-Lymphocytes ; *Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation ; Humans ; Lymphocyte Count ; RNA, Ribosomal, 16S ; Transplantation, Homologous ; }, abstract = {Low intestinal microbial diversity is associated with poor outcomes after allogeneic hematopoietic cell transplantation (HCT). Using 16S rRNA sequencing of 2067 stool samples and flow cytometry data from 2370 peripheral blood samples drawn from 894 patients who underwent allogeneic HCT, we have linked features of the early post-HCT microbiome with subsequent immune cell recovery. We examined lymphocyte recovery and microbiota features in recipients of both unmodified and CD34-selected allografts. We observed that fecal microbial diversity was an independent predictor of CD4 T-cell count 3 months after HCT in recipients of a CD34-selected allograft, who are dependent on de novo lymphopoiesis for their immune recovery. In multivariate models using clinical factors and microbiota features, we consistently observed that increased fecal relative abundance of genus Staphylococcus during the early posttransplant period was associated with worse CD4 T-cell recovery. Our observations suggest that the intestinal bacteria, or the factors they produce, can affect early lymphopoiesis and the homeostasis of allograft-derived T cells after transplantation.}, }
@article {pmid35060914, year = {2022}, author = {Chinna Meyyappan, A and Forth, E and Milev, R}, title = {Microbial Ecosystem Therapeutic-2 Intervention in People With Major Depressive Disorder and Generalized Anxiety Disorder: Phase 1, Open-Label Study.}, journal = {Interactive journal of medical research}, volume = {11}, number = {1}, pages = {e32234}, pmid = {35060914}, issn = {1929-073X}, abstract = {BACKGROUND: Recent studies have investigated the potential of treatments that modify the gut microbiome, such as fecal microbiota transplantation and probiotics, in individuals with psychiatric illnesses.<br><br>OBJECTIVE: The aim of this study was to investigate the safety, tolerability, and efficacy of a novel gut microbiome therapeutic, Microbial Ecosystem Therapuetic-2 (MET-2), in people with depression and anxiety.<br><br>METHODS: In this phase 1, open-label trial, 12 adults diagnosed with major depressive disorder, generalized anxiety disorder, or both were recruited. Over 8 weeks, participants consumed three capsules per day, orally, of an encapsulated microbial therapeutic (MET-2), which contained 40 strains of bacteria that were purified and lab-grown from the stool of a single healthy donor. Participants were assessed biweekly using clinical scales and questionnaires in order to evaluate the safety, efficacy, and tolerability of the therapeutic.<br><br>RESULTS: The therapeutic was found to be generally safe and tolerable, with limited adverse events and side effects and no serious adverse events. Of the 12 individuals included in this study, 9 (75%) responded to treatment (50% improvement in Montgomery-Asberg Depression Rating Scale [MADRS] scores, 7-item Generalized Anxiety Disorder scale [GAD-7] scores, or both, from baseline to the week-8 visit). Over the course of 10 weeks, MET-2 significantly decreased mean MADRS and GAD-7 scores (MADRS: F2.731, 30.05=8.784, P<.001; GAD-7: F2.778, 30.55= 9.638, P<.001). Multiple comparisons with Bonferroni adjustments showed a significant reduction in MADRS scores from baseline (mean 19.00, SD 4.843) to week 6 (mean 11.25, SD 8.001; P=.009), week 8 (mean 8.667, SD 8.732; P=.002), and week 10 (mean 8.250, SD 9.304; P=.006). Multiple comparisons showed a significant reduction in GAD-7 scores from baseline (mean 13.58, SD 4.010) to week 4 (mean 9.167, SD 5.096; P=.03), week 6 (mean 7.667, SD 4.539; P=.004), week 8 (mean 7.333, SD 6.583; P=.03), and week 10 (mean 7.500, SD 6.448; P=.03).<br><br>CONCLUSIONS: The findings from this study are the first to provide evidence for the role of microbial ecosystem therapy in treating depression and anxiety. However, a double-blind, randomized controlled trial with a larger sample size is needed for more conclusive results.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT04052451; https://www.clinicaltrials.gov/ct2/show/NCT04052451.<br><br>RR2-10.2196/17223.}, }
@article {pmid35060521, year = {2022}, author = {Li, J and Wang, D and Sun, J}, title = {Application of fecal microbial transplantation in hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.}, journal = {Medicine}, volume = {101}, number = {3}, pages = {e28584}, pmid = {35060521}, issn = {1536-5964}, support = {CYFY2017GLPXH002//the State Key Clinical Specially Construction Project, number CYFY2017GLPXH002/ ; }, mesh = {Adult ; Esophageal and Gastric Varices/diagnostic imaging ; *Fecal Microbiota Transplantation ; Gastrointestinal Hemorrhage/etiology ; *Gastrointestinal Microbiome ; Gastroscopy ; Hepatic Encephalopathy/etiology/*therapy ; Humans ; Hypertension, Portal/*surgery ; Liver Cirrhosis/complications ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Portal Vein/diagnostic imaging ; Portasystemic Shunt, Transjugular Intrahepatic/*adverse effects ; Treatment Outcome ; Varicose Veins/diagnostic imaging ; }, abstract = {RATIONALE: Transjugular intrahepatic portosystemic shunt (TIPS) is mainly used to treat acute and chronic esophageal, gastric, and intestinal variceal bleeding and refractory ascites caused by portal hypertension. The most common complication of TIPS is the development of hepatic encephalopathy (HE). Fecal microbiota transplantation (FMT) is an emerging method for treating diseases by altering the intestinal flora. We present 2 cases of FMT that ameliorated liver function and HE after TIPS.<br><br>PATIENT CONCERNS: In this report, 2 patients with liver cirrhosis secondary to hepatitis B had recurrent Grade 2-3 HE after TIPS.<br><br>DIAGNOSIS: Two patients were diagnosed as having HE.<br><br>INTERVENTIONS: The 2 patients separately received 3 times of FMT.<br><br>OUTCOMES: The liver function of both patients improved, the clinical symptoms were relieved, and the number of HE attacks decreased significantly after FMT.<br><br>LESSONS: FMT may be another effective way to treat HE, and is worthy of further research.}, }
@article {pmid35059329, year = {2021}, author = {Zuppi, M and Hendrickson, HL and O'Sullivan, JM and Vatanen, T}, title = {Phages in the Gut Ecosystem.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {822562}, pmid = {35059329}, issn = {2235-2988}, mesh = {Bacteria ; *Bacteriophages ; Ecosystem ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Viruses ; }, abstract = {Phages, short for bacteriophages, are viruses that specifically infect bacteria and are the most abundant biological entities on earth found in every explored environment, from the deep sea to the Sahara Desert. Phages are abundant within the human biome and are gaining increasing recognition as potential modulators of the gut ecosystem. For example, they have been connected to gastrointestinal diseases and the treatment efficacy of Fecal Microbiota Transplant. The ability of phages to modulate the human gut microbiome has been attributed to the predation of bacteria or the promotion of bacterial survival by the transfer of genes that enhance bacterial fitness upon infection. In addition, phages have been shown to interact with the human immune system with variable outcomes. Despite the increasing evidence supporting the importance of phages in the gut ecosystem, the extent of their influence on the shape of the gut ecosystem is yet to be fully understood. Here, we discuss evidence for phage modulation of the gut microbiome, postulating that phages are pivotal contributors to the gut ecosystem dynamics. We therefore propose novel research questions to further elucidate the role(s) that they have within the human ecosystem and its impact on our health and well-being.}, }
@article {pmid35058749, year = {2021}, author = {Hua, D and Li, S and Li, S and Wang, X and Wang, Y and Xie, Z and Zhao, Y and Zhang, J and Luo, A}, title = {Gut Microbiome and Plasma Metabolome Signatures in Middle-Aged Mice With Cognitive Dysfunction Induced by Chronic Neuropathic Pain.}, journal = {Frontiers in molecular neuroscience}, volume = {14}, number = {}, pages = {806700}, pmid = {35058749}, issn = {1662-5099}, abstract = {Patients with chronic neuropathic pain (CNP) often complain about their terrible memory, especially the speed of information processing. Accumulating evidence suggests a possible link between gut microbiota and pain processing as well as cognitive function via the microbiota-gut-brain axis. This study aimed at exploring the fecal microbiome and plasma metabolite profiles in middle-aged spared nerve injury (SNI) mice model with cognitive dysfunction (CD) induced by CNP. The hierarchical cluster analysis of performance in the Morris water maze test was used to classify SNI mice with CD or without CD [i.e., non-CD (NCD)] phenotype. 16S rRNA sequencing revealed a lower diversity of gut bacteria in SNI mice, and the increase of Actinobacteria, Proteus, and Bifidobacterium might contribute to the cognitive impairment in the CNP condition. The plasma metabolome analysis showed that the endocannabinoid (eCB) system, disturbances of lipids, and amino acid metabolism might be the dominant signatures of CD mice. The fecal microbiota transplantation of the Sham (not CD) group improved allodynia and cognitive performance in pseudo-germ-free mice via normalizing the mRNA expression of eCB receptors, such as cn1r, cn2r, and htr1a, reflecting the effects of gut bacteria on metabolic activity. Collectively, the findings of this study suggest that the modulation of gut microbiota and eCB signaling may serve as therapeutic targets for cognitive deficits in patients with CNP.}, }
@article {pmid35058059, year = {2022}, author = {Prado, C and Abatti, MR and Michels, M and Córneo, E and Cucker, L and Borges, H and Dias, R and Rocha, LB and Dal-Pizzol, F and Ritter, C}, title = {Comparative effects of fresh and sterile fecal microbiota transplantation in an experimental animal model of necrotizing enterocolitis.}, journal = {Journal of pediatric surgery}, volume = {57}, number = {9}, pages = {183-191}, doi = {10.1016/j.jpedsurg.2021.12.013}, pmid = {35058059}, issn = {1531-5037}, mesh = {Animals ; *Enterocolitis, Necrotizing/therapy ; Fecal Microbiota Transplantation ; Female ; *Fetal Diseases ; *Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; *Infant, Newborn, Diseases ; Inflammation/pathology ; Models, Animal ; Rats ; Rats, Wistar ; }, abstract = {INTRODUCTION: Necrotizing Enterocolitis (NEC) is a serious intestinal disease that affects premature neonates, causing high mortality, despite the technological development in neonatal intensive care, with antibiotics, parenteral nutrition, surgery, and advanced life support. The correction of dysbiosis with fecal microbiome transplantation (FMT) has shown beneficial effects in experimental models of the disease. The different forms of administration and conservation of FMT and mixed results depending on several factors lead to questions about the mechanism of action of FMT. This study aimed to compare the effectiveness of fresh, sterile FMT and probiotic treatment under parameters of inflammation, oxidative stress, and tissue damage in a neonatal model of NEC.<br><br>METHODS: One-day-old Wistar rats were used to induce NEC model. Animals were divided in five groups: Control&#xa0;+&#xa0;saline; NEC&#xa0;+&#xa0;saline; NEC&#xa0;+&#xa0;fresh FMT; NEC&#xa0;+&#xa0;sterile FMT and NEC+ probiotics. Parameters of inflammatory response and oxidative damage were measured in the gut, brain, and serum. It was also determined gut histopathological alterations.<br><br>RESULTS: Proinflammatory cytokines were increased in the NEC group, and IL-10 levels decreased in the gut, brain, and serum. Fresh and sterile FMT decreased inflammation when compared to the use of probiotics. Oxidative and histological damage to the intestine was apparent in the NEC group, and both FMT treatments had a protective effect.<br><br>CONCLUSION: Fresh and sterile FMT effectively reduced the inflammatory response, oxidative damage, and histological alterations in the gut and brain compared to an experimental NEC model.}, }
@article {pmid35057693, year = {2022}, author = {Jena, A and Mishra, S and Singh, AK and Sekar, A and Sharma, V}, title = {Cytomegalovirus in ulcerative colitis: an evidence-based approach to diagnosis and treatment.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {16}, number = {2}, pages = {109-120}, doi = {10.1080/17474124.2022.2032662}, pmid = {35057693}, issn = {1747-4132}, mesh = {Antiviral Agents/*therapeutic use ; Colitis, Ulcerative/*complications ; Colonoscopy ; Cytomegalovirus Infections/*diagnosis/*therapy ; Evidence-Based Medicine ; Fecal Microbiota Transplantation ; Ganciclovir/therapeutic use ; Humans ; Immunohistochemistry ; Immunosuppressive Agents/*therapeutic use ; Polymerase Chain Reaction ; Steroids/therapeutic use ; Tumor Necrosis Factor-alpha/antagonists &amp; inhibitors ; }, abstract = {INTRODUCTION: The detection of cytomegalovirus (CMV) in the setting of inflammatory bowel disease often creates confusion whether CMV is a 'bystander' or 'disease.'<br><br>AREAS COVERED: This review discusses the clinical conundrum of CMV in ulcerative colitis, approach to discriminate infection from disease, and therapeutic considerations (immunosuppressive and anti-CMV treatment). CMV disease should be considered in corticosteroid refractory- dependent and thiopurine refractory disease. Endoscopy may reveal deep punched out ulcers, irregular ulcers, or cobble-stoning. The diagnosis rests on the presence and abundance of viral inclusion bodies on hematoxylin and eosin stain, positive immunohistochemistry, and/or positive tissue polymerase chain reaction. CMV disease is associated with worse outcomes including increased colectomy rates.<br><br>EXPERT OPINION: The timing and duration of antiviral drugs in CMV disease is debatable but depends on the load of CMV in tissue. In high-grade infection, CMV needs to be treated while increasing immunosuppression may work in the setting of low-grade infection. Ganciclovir is the drug of choice for treatment of CMV disease. Tumor necrosis factor inhibitors may be useful for treating underlying disease activity in the setting of CMV. Other emerging therapies include fecal microbiota transplantation. Randomized studies are necessary to define the best timing and duration of anti-CMV therapy.}, }
@article {pmid35056521, year = {2021}, author = {Edwards, V and Smith, DL and Meylan, F and Tiffany, L and Poncet, S and Wu, WW and Phue, JN and Santana-Quintero, L and Clouse, KA and Gabay, O}, title = {Analyzing the Role of Gut Microbiota on the Onset of Autoimmune Diseases Using TNF[ΔARE] Murine Model.}, journal = {Microorganisms}, volume = {10}, number = {1}, pages = {}, pmid = {35056521}, issn = {2076-2607}, support = {P30 DK097948/DK/NIDDK NIH HHS/United States ; }, abstract = {Very little is known about disease transmission via the gut microbiome. We hypothesized that certain inflammatory features could be transmitted via the gut microbiome and tested this hypothesis using an animal model of inflammatory diseases. Twelve-week-old healthy C57 Bl/6 and Germ-Free (GF) female and male mice were fecal matter transplanted (FMT) under anaerobic conditions with TNF[ΔARE-/+] donors exhibiting spontaneous Rheumatoid Arthritis (RA) and Inflammatory Bowel Disease (IBD) or with conventional healthy mice control donors. The gut microbiome analysis was performed using 16S rRNA sequencing amplification and bioinformatics analysis with the HIVE bioinformatics platform. Histology, immunohistochemistry, ELISA Multiplex analysis, and flow cytometry were conducted to confirm the inflammatory transmission status. We observed RA and IBD features transmitted in the GF mice cohort, with gut tissue disruption, cartilage alteration, elevated inflammatory mediators in the tissues, activation of CD4/CD8+ T cells, and colonization and transmission of the gut microbiome similar to the donors' profile. We did not observe a change or transmission when conventional healthy mice were FMT with TNF[ΔARE-/+] donors, suggesting that a healthy microbiome might withstand an unhealthy transplant. These findings show the potential involvement of the gut microbiome in inflammatory diseases. We identified a cluster of bacteria playing a role in this mechanism.}, }
@article {pmid35056472, year = {2021}, author = {Masucci, L and Quaranta, G}, title = {Fecal Microbiota Transplantation: What's New?.}, journal = {Microorganisms}, volume = {10}, number = {1}, pages = {}, pmid = {35056472}, issn = {2076-2607}, abstract = {The gut microbiota is composed of trillions of different microorganisms: bacteria, archaea, phages and protozoa, which represent a real solid organ, with an approximate weight of 2 kg [...].}, }
@article {pmid35056392, year = {2022}, author = {Tkach, S and Dorofeyev, A and Kuzenko, I and Boyko, N and Falalyeyeva, T and Boccuto, L and Scarpellini, E and Kobyliak, N and Abenavoli, L}, title = {Current Status and Future Therapeutic Options for Fecal Microbiota Transplantation.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {1}, pages = {}, pmid = {35056392}, issn = {1648-9144}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, abstract = {The intestinal microbiota plays an important role in maintaining human health, and its alteration is now associated with the development of various gastrointestinal (ulcerative colitis, irritable bowel syndrome, constipation, etc.) and extraintestinal diseases, such as cancer, metabolic syndrome, neuropsychiatric diseases. In this context, it is not surprising that gut microbiota modification methods may constitute a therapy whose potential has not yet been fully investigated. In this regard, the most interesting method is thought to be fecal microbiota transplantation, which consists of the simultaneous replacement of the intestinal microbiota of a sick recipient with fecal material from a healthy donor. This review summarizes the most interesting findings on the application of fecal microbiota transplantation in gastrointestinal and extraintestinal pathologies.}, }
@article {pmid35054136, year = {2022}, author = {Herman, A and Herman, AP}, title = {Could Candida Overgrowth Be Involved in the Pathophysiology of Autism?.}, journal = {Journal of clinical medicine}, volume = {11}, number = {2}, pages = {}, pmid = {35054136}, issn = {2077-0383}, abstract = {The purpose of this review is to summarize the current acquiredknowledge of Candida overgrowth in the intestine as a possible etiology of autism spectrum disorder (ASD). The influence of Candida sp. on the immune system, brain, and behavior of children with ASD isdescribed. The benefits of interventions such as a carbohydrates-exclusion diet, probiotic supplementation, antifungal agents, fecal microbiota transplantation (FMT), and microbiota transfer therapy (MTT) will be also discussed. Our literature query showed that the results of most studies do not fully support the hypothesis that Candida overgrowth is correlated with gastrointestinal (GI) problems and contributes to autism behavioral symptoms occurrence. On the one hand, it was reported that the modulation of microbiota composition in the gut may decrease Candida overgrowth, help reduce GI problems and autism symptoms. On the other hand, studies on humans suggesting the beneficial effects of a sugar-free diet, probiotic supplementation, FMT and MTT treatment in ASD are limited and inconclusive. Due to the increasing prevalence of ASD, studies on the etiology of this disorder are extremely needed and valuable. However, to elucidate the possible involvement of Candida in the pathophysiology of ASD, more reliable and well-designed research is certainly required.}, }
@article {pmid35053205, year = {2021}, author = {Vallianou, N and Christodoulatos, GS and Karampela, I and Tsilingiris, D and Magkos, F and Stratigou, T and Kounatidis, D and Dalamaga, M}, title = {Understanding the Role of the Gut Microbiome and Microbial Metabolites in Non-Alcoholic Fatty Liver Disease: Current Evidence and Perspectives.}, journal = {Biomolecules}, volume = {12}, number = {1}, pages = {}, pmid = {35053205}, issn = {2218-273X}, mesh = {*Carcinoma, Hepatocellular/metabolism ; Child ; Dysbiosis/metabolism ; *Gastrointestinal Microbiome/genetics ; Humans ; Liver/metabolism ; *Liver Neoplasms/metabolism ; *Non-alcoholic Fatty Liver Disease/pathology ; Prospective Studies ; RNA, Ribosomal, 16S/metabolism ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD begins as a relatively benign hepatic steatosis which can evolve to non-alcoholic steatohepatitis (NASH); the risk of cirrhosis and hepatocellular carcinoma (HCC) increases when fibrosis is present. NAFLD represents a complex process implicating numerous factors-genetic, metabolic, and dietary-intertwined in a multi-hit etiopathogenetic model. Recent data have highlighted the role of gut dysbiosis, which may render the bowel more permeable, leading to increased free fatty acid absorption, bacterial migration, and a parallel release of toxic bacterial products, lipopolysaccharide (LPS), and proinflammatory cytokines that initiate and sustain inflammation. Although gut dysbiosis is present in each disease stage, there is currently no single microbial signature to distinguish or predict which patients will evolve from NAFLD to NASH and HCC. Using 16S rRNA sequencing, the majority of patients with NAFLD/NASH exhibit increased numbers of Bacteroidetes and differences in the presence of Firmicutes, resulting in a decreased F/B ratio in most studies. They also present an increased proportion of species belonging to Clostridium, Anaerobacter, Streptococcus, Escherichia, and Lactobacillus, whereas Oscillibacter, Flavonifaractor, Odoribacter, and Alistipes spp. are less prominent. In comparison to healthy controls, patients with NASH show a higher abundance of Proteobacteria, Enterobacteriaceae, and Escherichia spp., while Faecalibacterium prausnitzii and Akkermansia muciniphila are diminished. Children with NAFLD/NASH have a decreased proportion of Oscillospira spp. accompanied by an elevated proportion of Dorea, Blautia, Prevotella copri, and Ruminococcus spp. Gut microbiota composition may vary between population groups and different stages of NAFLD, making any conclusive or causative claims about gut microbiota profiles in NAFLD patients challenging. Moreover, various metabolites may be involved in the pathogenesis of NAFLD, such as short-chain fatty acids, lipopolysaccharide, bile acids, choline and trimethylamine-N-oxide, and ammonia. In this review, we summarize the role of the gut microbiome and metabolites in NAFLD pathogenesis, and we discuss potential preventive and therapeutic interventions related to the gut microbiome, such as the administration of probiotics, prebiotics, synbiotics, antibiotics, and bacteriophages, as well as the contribution of bariatric surgery and fecal microbiota transplantation in the therapeutic armamentarium against NAFLD. Larger and longer-term prospective studies, including well-defined cohorts as well as a multi-omics approach, are required to better identify the associations between the gut microbiome, microbial metabolites, and NAFLD occurrence and progression.}, }
@article {pmid35052569, year = {2021}, author = {Chen, ZY and Xiao, HW and Dong, JL and Li, Y and Wang, B and Fan, SJ and Cui, M}, title = {Gut Microbiota-Derived PGF2α Fights against Radiation-Induced Lung Toxicity through the MAPK/NF-κB Pathway.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {35052569}, issn = {2076-3921}, support = {32100087, 81872555, 82003399, and 82173467//National Natural Science Foundation of China/ ; 20JCJQJC00100//he Science Foundation for Distinguished Young Scholars of Tianjin/ ; }, abstract = {Radiation pneumonia is a common and intractable side effect associated with radiotherapy for chest cancer and involves oxidative stress damage and inflammation, prematurely halting the remedy and reducing the life quality of patients. However, the therapeutic options for the complication have yielded disappointing results in clinical application. Here, we report an effective avenue for fighting against radiation pneumonia. Faecal microbiota transplantation (FMT) reduced radiation pneumonia, scavenged oxidative stress and improved lung function in mouse models. Local chest irradiation shifted the gut bacterial taxonomic proportions, which were preserved by FMT. The level of gut microbiota-derived PGF2α decreased following irradiation but increased after FMT. Experimental mice with PGF2α replenishment, via an oral route, exhibited accumulated PGF2α in faecal pellets, peripheral blood and lung tissues, resulting in the attenuation of inflammatory status of the lung and amelioration of lung respiratory function following local chest irradiation. PGF2α activated the FP/MAPK/NF-κB axis to promote cell proliferation and inhibit apoptosis with radiation challenge; silencing MAPK attenuated the protective effect of PGF2α on radiation-challenged lung cells. Together, our findings pave the way for the clinical treatment of radiotherapy-associated complications and underpin PGF2α as a gut microbiota-produced metabolite.}, }
@article {pmid35050941, year = {2023}, author = {Beran, A and Sharma, S and Ghazaleh, S and Lee-Smith, W and Aziz, M and Kamal, F and Acharya, A and Adler, DG}, title = {Predictors of Fecal Microbiota Transplant Failure in Clostridioides difficile Infection : An Updated Meta-analysis.}, journal = {Journal of clinical gastroenterology}, volume = {57}, number = {4}, pages = {389-399}, doi = {10.1097/MCG.0000000000001667}, pmid = {35050941}, issn = {1539-2031}, mesh = {Humans ; Female ; Male ; Fecal Microbiota Transplantation/adverse effects/methods ; *Clostridioides difficile ; Recurrence ; *Clostridium Infections/therapy ; Treatment Outcome ; }, abstract = {INTRODUCTION AND AIM: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent/refractory Clostridioides difficile infection (CDI) with a 10% to 20% risk of recurrence after a single FMT. In this meta-analysis, we aimed to evaluate the predictors of FMT failure.<br><br>METHODS: A comprehensive search of MEDLINE, Embase, Cochrane, and Web of Science databases through July 2021 was performed. All studies that evaluated risk factors associated with FMT failure in a multivariate model were included. We calculated pooled odds ratios with 95% confidence intervals for risk factors reported in &#x2265;3 studies using a random-effects model.<br><br>RESULTS: Twenty studies involving 4327 patients (63.6% females) with recurrent/refractory CDI who underwent FMT were included. FMT failed in 705 patients (16.3%) with 2 to 3 months of follow-up in most studies. A total of 12 different risk factors were reported in a multivariate model in &#x2265;3 studies. Meta-analysis showed that advanced age, severe CDI, inflammatory bowel disease, peri-FMT use of non-CDI antibiotics, prior CDI-related hospitalizations, inpatient status, and poor quality of bowel preparation were significant predictors of FMT failure. Charlson Comorbidity Index, female gender, immunosuppressed status, patient-directed donor, and number of CDI recurrences were not associated with FMT failure.<br><br>CONCLUSIONS: Adequate bowel preparation at the time of FMT and optimizing antibiotic stewardship practices in the peri-FMT period can improve the success of FMT. Patients with nonmodifiable risk factors should be counseled about the risk of FMT failure. Our results may help develop a risk stratification model to predict FMT failure in CDI patients.}, }
@article {pmid35046929, year = {2021}, author = {König, RS and Albrich, WC and Kahlert, CR and Bahr, LS and Löber, U and Vernazza, P and Scheibenbogen, C and Forslund, SK}, title = {The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS).}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {628741}, pmid = {35046929}, issn = {1664-3224}, mesh = {Animals ; Brain-Gut Axis/*physiology ; Fatigue Syndrome, Chronic/*microbiology/*physiopathology ; Gastrointestinal Microbiome/*physiology ; Humans ; }, abstract = {Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed. We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients. Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.}, }
@article {pmid35046924, year = {2021}, author = {Qiao, Y and Zhang, Z and Zhai, Y and Yan, X and Zhou, W and Liu, H and Guan, L and Peng, L}, title = {Apigenin Alleviates Obesity-Associated Metabolic Syndrome by Regulating the Composition of the Gut Microbiome.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {805827}, pmid = {35046924}, issn = {1664-302X}, abstract = {The gut microbiota, often viewed as a "digestive organ," can influence the development of obesity and related metabolic disorders. Diet is significantly important in shaping the structure and modulating the function of the gut microbiota. Apigenin (Api) widely exists in fruits and vegetables as a naturally occurring flavonoid and has anti-obesogenic, anti-inflammatory, and anti-carcinogenic properties. Its low bioavailability means it has enough time to interact with the intestine thus becomes a potential substrate for the gut intestine; thus, contributing to gut health. Here, we show that Api reduces whole-body weight, low-grade inflammation, and insulin resistance in high-fat diet (HFD)-induced obese mice. Our results reflect that Api supplementation can substantially improve intestinal dysbiosis triggered by HFD and restores gut barrier damage by alleviating metabolic endotoxemia. Augmentation of Akkermansia and Incertae_Sedis along with reduction of Faecalibaculum and Dubosiella at the genus level potentially mediated the protective effects of Api on metabolic syndrome. Furthermore, we show that the impact of Api on the reduction of body weight and the modification of gut microbiota could be transferred from Api-administered mice to HFD-feeding mice via horizontal fecal microbiota transplantation. Taken together, our data highlight the prebiotic role of Api and show its contribution to the restraint of gut dysbiosis and metabolic deterioration associated with obesity in mice.}, }
@article {pmid35045605, year = {2023}, author = {Kang, SH and Gweon, TG and Hwang, H and Baeg, MK}, title = {Ischemic colitis complicated by Clostridioides difficile infection treated with fecal microbiota transplantation.}, journal = {Clinical endoscopy}, volume = {56}, number = {5}, pages = {666-670}, pmid = {35045605}, issn = {2234-2400}, support = {2021R1G1A1094049//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; }, abstract = {Ischemic colitis is an inflammatory condition of the colon that results from insufficient blood supply commonly caused by enterocolitis, vessel occlusion, or shock. In contrast, pseudomembranous colitis is a clinical manifestation of Clostridioides difficile infection (CDI). Ischemic colitis caused by CDI has rarely been reported. Fecal microbiota transplantation (FMT) is an efficient treatment for refractory or fulminant CDI, and the indications for its use have recently expanded. However, performing FMT in patients with ischemic colitis is challenging because of the risk of perforation. Here, we have presented a case of ischemic colitis caused by CDI that was successfully treated with FMT via sigmoidoscopy.}, }
@article {pmid35045306, year = {2022}, author = {Huang, G and Wang, L and Li, J and Hou, R and Wang, M and Wang, Z and Qu, Q and Zhou, W and Nie, Y and Hu, Y and Ma, Y and Yan, L and Wei, H and Wei, F}, title = {Seasonal shift of the gut microbiome synchronizes host peripheral circadian rhythm for physiological adaptation to a low-fat diet in the giant panda.}, journal = {Cell reports}, volume = {38}, number = {3}, pages = {110203}, doi = {10.1016/j.celrep.2021.110203}, pmid = {35045306}, issn = {2211-1247}, mesh = {Adaptation, Physiological/*physiology ; Animals ; Butyrates/metabolism ; Circadian Rhythm/*physiology ; Diet, Fat-Restricted ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions/*physiology ; Mice ; Period Circadian Proteins/metabolism ; Plant Leaves ; Plant Shoots ; Seasons ; Ursidae/*microbiology/physiology ; }, abstract = {Characteristics of the gut microbiome vary synchronously with changes in host diet. However, the underlying effects of these fluctuations remain unclear. Here, we performed fecal microbiota transplantation (FMT) of diet-specific feces from an endangered mammal (the giant panda) into a germ-free mouse model. We demonstrated that the butyrate-producing bacterium Clostridium butyricum was more abundant during shoot-eating season than during the leaf-eating season, congruent with the significant increase in host body mass. Following season-specific FMT, the microbiota of the mouse model resembled that of the donor, and mice transplanted with the microbiota from the shoot-eating season grew faster and stored more fat. Mechanistic investigations revealed that butyrate extended the upregulation of hepatic circadian gene Per2, subsequently increasing phospholipid biosynthesis. Validation experiments further confirmed this causal relationship. This study demonstrated that seasonal shifts in the gut microbiome affect growth performance, facilitating a deeper understanding of host-microbe interactions in wild mammals.}, }
@article {pmid35043436, year = {2022}, author = {Hinchliffe, T and Pauline, ML and Wizzard, PR and Jovel, J and Nation, PN and Wales, PW and Madsen, KL and Turner, JM}, title = {The effect of fecal microbial transplant on intestinal microbial composition in short-bowel neonatal piglets.}, journal = {JPEN. Journal of parenteral and enteral nutrition}, volume = {46}, number = {6}, pages = {1393-1403}, doi = {10.1002/jpen.2333}, pmid = {35043436}, issn = {1941-2444}, mesh = {Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; Feces ; Intestines ; *Sepsis/therapy ; *Short Bowel Syndrome/therapy ; Swine ; }, abstract = {BACKGROUND: Short-bowel syndrome (SBS) in neonates is associated with microbial dysbiosis due to intestinal surgery, prolonged hospitalization, enteral nutrition, and repeated antibiotic exposure. Sepsis and liver disease, leading causes of morbidity and mortality in SBS, may relate to such intestinal dysbiosis. We investigated the safety and feasibility of fecal microbial transplant (FMT) to alter intestinal microbial composition in SBS piglets.<br><br>METHODS: Following a 75% distal small-intestinal resection, piglets were fed parenteral nutrition with an elemental diet and randomized to saline (SAL; n&#x2009;=&#x2009;12) or FMT (n&#x2009;=&#x2009;12) treatments delivered by gastric tube on day 2 (d2). The FMT donor was a healthy adult pig. Comparisons were also made to healthy sow-fed littermate controls (SOW; n&#x2009;=&#x2009;6). Stool samples were collected daily, and tissue samples were collected at baseline and termination. Microbial DNA was extracted from stool and analyzed using 16S ribosomal RNA sequencing.<br><br>RESULTS: All piglets survived to the end point. On d2-d4, FMT piglets had some differences in microbiota composition compared with SAL, SOW, and donor counterparts. Between base and term, there were transitory changes to alpha and beta diversity in FMT and SAL.<br><br>CONCLUSION: FMT treatment in postsurgical neonatal piglets with SBS appears safe, with no increase in sepsis and no mortality. In SBS piglets, FMT induced transient changes to the intestinal microbiota. However, these changes did not persist long-term.}, }
@article {pmid35040733, year = {2022}, author = {Gallo, C and Howardson, BO and Cristoferi, L and Carbone, M and Gershwin, ME and Invernizzi, P}, title = {An update on novel pharmacological agents for primary sclerosing cholangitis.}, journal = {Expert opinion on therapeutic targets}, volume = {26}, number = {1}, pages = {69-77}, doi = {10.1080/14728222.2022.2030707}, pmid = {35040733}, issn = {1744-7631}, mesh = {Bile Acids and Salts/therapeutic use ; *Cholangitis, Sclerosing/drug therapy ; *Gastrointestinal Microbiome ; Humans ; *Liver Transplantation ; }, abstract = {INTRODUCTION: Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease with heterogeneous phenotypes that may lead to liver transplantation and/or end-stage liver disease. Its multifactorial etiopathogenesis remains uncertain, but gut-liver axis and bile composition and excretion are widely demonstrated to influence the immune-mediated fibrogenic reactive cascade.<br><br>AREAS COVERED: Different experimental therapeutic options are under investigation, mainly aiming at modulating bile acids excretion, limiting inflammatory-cascade reactions, and changing intestinal microbiota composition; none of them yet demonstrated to prolong transplant-free survival.This review provides a comprehensive description of the experimental drugs recently tested and/or currently under investigation. A bibliographical search was performed in PubMed, MEDLINE, EMBASE, OVID, and clinicaltrial.gov until July 2021.<br><br>EXPERT OPINION: The heterogeneity and poor prevalence of PSC, its uncertain pathophysiology, and the lack of surrogate endpoints are the major challenges in drug discovery. Strategies that synergistically target microbiota, bile acids, and liver fibrosis are needed. In parallel, we must enhance biomarkers discovery to develop surrogate endpoints, as biochemical markers' fluctuations over the time hamper their effectiveness. Magnetic resonance cholangiopancreatography tools that accurately measure bile duct changes represent a potential marker for disease monitoring. A collaboration between academia, research consortia, patient's associations, and industry is required.}, }
@article {pmid35040380, year = {2022}, author = {Wang, Y and Cui, B and Zhang, F}, title = {Refractory ulcerative colitis stabilized by interval washed microbiota transplantation: less is more.}, journal = {Current medical research and opinion}, volume = {38}, number = {4}, pages = {531-534}, doi = {10.1080/03007995.2022.2030563}, pmid = {35040380}, issn = {1473-4877}, mesh = {*Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation/methods ; Feces ; *Gastrointestinal Microbiome ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {Ulcerative colitis (UC) is an autoimmune inflammatory disorder characterized by a relapsing and remitting course. The gut microbiota is implicated in the pathogenesis of UC. Fecal microbiota transplant (FMT) has been reported as a rescue therapy for refractory UC. The newly improved methodology of FMT was recently coined as washed microbiota transplantation (WMT) based on the automatic purification system and washing process. Colonic transendoscopic enteral tubing (TET) is a novel delivery of WMT within the whole colon. In this case, the patient with refractory UC underwent two different strategies of fresh FMT. The prior strategy conducted daily FMT through the percutaneous endoscopic cecostomy (PEC) tube for 60 days. We performed WMT every 3-35 months by colonic TET or gastroscopy. The patient was effectively responsive to both strategies. The repeated interval WMTs induced long-term clinical remission for the patient. The case encouraged the physicians to consider repeated interval WMTs into practice as a long-term treatment strategy for refractory UC. Moreover, we hope more physicians and researchers would be inspired to study clinical strategies, such as optimizing the frequency and interval of WMTs and the related delivering strategy.}, }
@article {pmid35040302, year = {2021}, author = {Larussa, T and Abenavoli, L and Fabiano, G and Mancuso, MA and Polimeni, N and Dumitrascu, DL and Luzza, F}, title = {Gut microbiota in inflammatory bowel disease: a target for therapy not to be missed.}, journal = {Minerva gastroenterology}, volume = {67}, number = {4}, pages = {357-368}, doi = {10.23736/S2724-5985.21.02907-7}, pmid = {35040302}, issn = {2724-5365}, mesh = {Chronic Disease ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy ; }, abstract = {In the last years, the gut microbiota achieved great importance, since several studies demonstrated its correlation with the immune system and with the maintenance of intestinal homeostasis, as well as with the regulation of the integrity of the epithelium and the intestinal motility. An imbalance in microbial species promotes a dysbiosis, which has been associated with chronic diseases such as metabolic syndrome, inflammatory diseases, and some behavior disorders. The association with gut microbiota and dysbiosis has been demonstrated mostly in inflammatory bowel disease (IBD). Several studies investigated the application of antibiotics, prebiotics, probiotics, and fecal microbiota transplantation in the treatment strategies for IBD. In this review, we discuss the recent findings on the potential role of the gut microbiota manipulation, with particular attention to bacterial microbiota, which could be implicated for a successful IBD therapeutic approach.}, }
@article {pmid35037353, year = {2022}, author = {Benech, N and Legendre, P and Radoszycki, L and Varriale, P and Sokol, H}, title = {Patient knowledge of gut microbiota and acceptability of fecal microbiota transplantation in various diseases.}, journal = {Neurogastroenterology and motility}, volume = {34}, number = {8}, pages = {e14320}, doi = {10.1111/nmo.14320}, pmid = {35037353}, issn = {1365-2982}, mesh = {*Diabetes Mellitus, Type 2 ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Male ; *Microbiota ; *Probiotics ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is now evaluated in various diseases. However, large-scale population treatment may encounter feasibility issues in terms of acceptance. We aim to evaluate patient knowledge of gut microbiota and the acceptability of FMT in various diseases.<br><br>METHODS: Patients of Carenity's French online community were invited by email to participate in a questionnaire. The following parameters were assessed: patient's principal illness and duration, demographic data, therapeutics, dietary habits, knowledge of gut microbiota, probiotics and FMT, and its acceptability.<br><br>KEY RESULTS: In total, 877 patients participated in the online questionnaire: 156 with inflammatory bowel disease (17.8%), 127 with rheumatoid arthritis (14.5%), 222 with ankylosing spondylitis (25.3%), 52 with lupus (5.9%), 64 with psoriasis (7.3%), 61 with obesity (7%), and 195 with type 2 diabetes (22.2%). Characteristics of participating patients were similar to those of the entire cohort (n&#xa0;=&#xa0;23084). Overall, 47.1% (n&#xa0;=&#xa0;413/877) of patients knew what the microbiota is with no difference among diseases. Knowledge was reported to be developed by patients themselves (203/413; 49.2%) without involving a healthcare professional. If proposed by a healthcare professional, 37.2% (326/877) reported being interested or very interested in undergoing FMT. Factors associated with good acceptability of FMT were the male sex (OR: 1.63, CI95% [1.14 to 2.32]), previous knowledge of FMT (OR: 4.16, CI95% [2.92 to 5.96]), and previous knowledge of gut microbiota (OR: 1.54, CI95% [1.05 to 2.24]).<br><br>CONCLUSION AND INFERENCES: Knowledge of gut microbiota is still limited in patients' communities and mainly developed by patients themselves, impacting FMT acceptability.}, }
@article {pmid35035748, year = {2021}, author = {Lei, D and Xu, H and Peng, R and Yang, M and Li, X and Zuo, W and Gou, J and Yu, S and Huang, M and Liu, H}, title = {Efficacy of faecal microbiota transplantation on ulcerative colitis and its effect on gastrointestinal motility and immune function.}, journal = {American journal of translational research}, volume = {13}, number = {12}, pages = {14057-14066}, pmid = {35035748}, issn = {1943-8141}, abstract = {OBJECTIVE: To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of ulcerative colitis (UC) and its effect on gastrointestinal motility (GM) and immune function.<br><br>METHODS: A retrospective cohort study was conducted on 47 UC patients. The patients were divided into an observation group (n=17, treated with FMT) and a control group (n=30, treated with conventional treatment) according to the treatment regimen. In the observation group, FMT was used to treat colonic lesions by transplanting colonic bacteria fluid from healthy people. Clinical efficacy, immune function, level of inflammatory factors and gastrointestinal function of the two groups were observed before and after treatment.<br><br>RESULTS: The total response rates of observation group was 94.12%, which was higher than that of control group (70.00%; P<0.05). After treatment, the contents of CD3+, CD4+ T cells and CD4+/CD8+ ratio were increased, while the content of CD8+ T cells was decreased in both groups compared with those before treatment (all P<0.05); and the contents of CD3+, CD4+ T cells and CD4+/CD8+ ratio in the observation group were higher than those in the control group, while CD8+ T cells showed an opposite trend (P<0.05). The levels of immunoglobulin A, immunoglobulin G and immunoglobulin M as well as interleukin-6, C-reactive protein, tumor necrosis factor-&#x3b1; and motilin were lower than those before treatment in both groups (all P<0.05), and the decreases in the observation group were more significant than those in the control group (all P<0.001). After treatment, cholecystokinin and vasoactive peptide were higher than those before treatment in both groups (all P<0.05), and the increased degree in the observation group was more obvious than that in the control group (all P<0.001).<br><br>CONCLUSION: FMT has significant clinical efficacy in the treatment of UC, which may be related to the improvement of immune function, alleviation of inflammatory response and promotion of GM recovery.}, }
@article {pmid35032499, year = {2022}, author = {Priyadarshini, M and Navarro, G and Reiman, DJ and Sharma, A and Xu, K and Lednovich, K and Manzella, CR and Khan, MW and Garcia, MS and Allard, S and Wicksteed, B and Chlipala, GE and Szynal, B and Bernabe, BP and Maki, PM and Gill, RK and Perdew, GH and Gilbert, J and Dai, Y and Layden, BT}, title = {Gestational Insulin Resistance Is Mediated by the Gut Microbiome-Indoleamine 2,3-Dioxygenase Axis.}, journal = {Gastroenterology}, volume = {162}, number = {6}, pages = {1675-1689.e11}, pmid = {35032499}, issn = {1528-0012}, support = {R01 DK104927/DK/NIDDK NIH HHS/United States ; F30 DK113703/DK/NIDDK NIH HHS/United States ; R35 ES028244/ES/NIEHS NIH HHS/United States ; K12 HD101373/HD/NICHD NIH HHS/United States ; I01 BX003382/BX/BLRD VA/United States ; P30 DK020595/DK/NIDDK NIH HHS/United States ; R03 HD095056/HD/NICHD NIH HHS/United States ; R01 DK098170/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Female ; *Gastrointestinal Microbiome ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/metabolism ; Inflammation ; *Insulin Resistance ; Kynurenine/metabolism ; Mice ; Pregnancy ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND &amp; AIMS: Normal gestation involves a reprogramming of the maternal gut microbiome (GM) that contributes to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of the GM-maternal metabolism interaction.<br><br>METHODS: The GM and plasma metabolome of CD1, NIH-Swiss, and C57 mice were analyzed with the use of 16S rRNA sequencing and untargeted liquid chromatography-mass spectrometry throughout gestation. Pharmacologic and genetic knockout mouse models were used to identify the role of indoleamine 2,3-dioxygenase (IDO1) in pregnancy-associated insulin resistance (IR). Involvement of gestational GM was studied with the use of fecal microbial transplants (FMTs).<br><br>RESULTS: Significant variation in GM alpha diversity occurred throughout pregnancy. Enrichment in gut bacterial taxa was mouse strain and pregnancy time point specific, with the species enriched at gestation day 15/19 (G15/19), a point of heightened IR, being distinct from those enriched before or after pregnancy. Metabolomics revealed elevated plasma kynurenine at G15/19 in all 3 mouse strains. IDO1, the rate-limiting enzyme for kynurenine production, had increased intestinal expression at G15, which was associated with mild systemic and gut inflammation. Pharmacologic and genetic inhibition of IDO1 inhibited kynurenine levels and reversed pregnancy-associated IR. FMT revealed that IDO1 induction and local kynurenine level effects on IR derive from the GM in both mouse and human pregnancy.<br><br>CONCLUSIONS: GM changes accompanying pregnancy shift IDO1-dependent tryptophan metabolism toward kynurenine production, intestinal inflammation, and gestational IR, a phenotype reversed by genetic deletion or inhibition of IDO1. (Gestational Gut Microbiome-IDO1 Axis Mediates Pregnancy Insulin Resistance; EMBL-ENA ID: PRJEB45047. MetaboLights ID: MTBLS3598).}, }
@article {pmid35031549, year = {2022}, author = {Messaoudene, M and Pidgeon, R and Richard, C and Ponce, M and Diop, K and Benlaifaoui, M and Nolin-Lapalme, A and Cauchois, F and Malo, J and Belkaid, W and Isnard, S and Fradet, Y and Dridi, L and Velin, D and Oster, P and Raoult, D and Ghiringhelli, F and Boidot, R and Chevrier, S and Kysela, DT and Brun, YV and Falcone, EL and Pilon, G and Oñate, FP and Gitton-Quent, O and Le Chatelier, E and Durand, S and Kroemer, G and Elkrief, A and Marette, A and Castagner, B and Routy, B}, title = {A Natural Polyphenol Exerts Antitumor Activity and Circumvents Anti-PD-1 Resistance through Effects on the Gut Microbiota.}, journal = {Cancer discovery}, volume = {12}, number = {4}, pages = {1070-1087}, pmid = {35031549}, issn = {2159-8290}, support = {//CIHR/Canada ; }, mesh = {Animals ; Bacteria ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; Polyphenols/pharmacology/therapeutic use ; }, abstract = {UNLABELLED: Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC; Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti-PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC. Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/FOXP3+CD4+ ratio within the tumor microenvironment. Moreover, castalagin induced metabolic changes, resulting in an increase in taurine-conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti-PD-1 activity. Finally, we found that castalagin binds to Ruminococcus bromii and promoted an anticancer response. Altogether, our results identify castalagin as a polyphenol that acts as a prebiotic to circumvent anti-PD-1 resistance.<br><br>SIGNIFICANCE: The polyphenol castalagin isolated from a berry has an antitumor effect through direct interactions with commensal bacteria, thus reprogramming the tumor microenvironment. In addition, in preclinical ICI-resistant models, castalagin reestablishes the efficacy of anti-PD-1. Together, these results provide a strong biological rationale to test castalagin as part of a clinical trial. This article is highlighted in the In This Issue feature, p. 873.}, }
@article {pmid35028606, year = {2021}, author = {Blake, SJ and James, J and Ryan, FJ and Caparros-Martin, J and Eden, GL and Tee, YC and Salamon, JR and Benson, SC and Tumes, DJ and Sribnaia, A and Stevens, NE and Finnie, JW and Kobayashi, H and White, DL and Wesselingh, SL and O'Gara, F and Lynn, MA and Lynn, DJ}, title = {The immunotoxicity, but not anti-tumor efficacy, of anti-CD40 and anti-CD137 immunotherapies is dependent on the gut microbiota.}, journal = {Cell reports. Medicine}, volume = {2}, number = {12}, pages = {100464}, pmid = {35028606}, issn = {2666-3791}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Antineoplastic Agents/*pharmacology ; Bile Acids and Salts/metabolism ; CD40 Antigens/*immunology ; Cytokine Release Syndrome/immunology/pathology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Germ-Free Life ; Immunotherapy/*adverse effects ; Inflammation/pathology ; Interferon Type I/metabolism ; Lipid Metabolism/drug effects ; Liver/drug effects/immunology/metabolism/pathology ; Mice, Inbred C57BL ; Myeloid Differentiation Factor 88/metabolism ; Signal Transduction/drug effects ; Tumor Necrosis Factor Receptor Superfamily, Member 9/*immunology ; Tumor Necrosis Factor-alpha/metabolism ; Mice ; }, abstract = {Immune agonist antibodies (IAAs) are promising immunotherapies that target co-stimulatory receptors to induce potent anti-tumor immune responses, particularly when combined with checkpoint inhibitors. Unfortunately, their clinical translation is hampered by serious dose-limiting, immune-mediated toxicities, including high-grade and sometimes fatal liver damage, cytokine release syndrome (CRS), and colitis. We show that the immunotoxicity, induced by the IAAs anti-CD40 and anti-CD137, is dependent on the gut microbiota. Germ-free or antibiotic-treated mice have significantly reduced colitis, CRS, and liver damage following IAA treatment compared with conventional mice or germ-free mice recolonized via fecal microbiota transplant. MyD88 signaling is required for IAA-induced CRS and for anti-CD137-induced, but not anti-CD40-induced, liver damage. Importantly, antibiotic treatment does not impair IAA anti-tumor efficacy, alone or in combination with anti-PD1. Our results suggest that microbiota-targeted therapies could overcome the toxicity induced by IAAs without impairing their anti-tumor activity.}, }
@article {pmid35026167, year = {2022}, author = {Inglis, D and Quraishi, MN and Green, C and Iqbal, T}, title = {The growth of faecal microbiota transplantation in the UK: time for a registry?.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {2}, pages = {112-114}, doi = {10.1016/S2468-1253(21)00436-2}, pmid = {35026167}, issn = {2468-1253}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous/therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; *Registries ; State Medicine ; United Kingdom ; }, }
@article {pmid35024588, year = {2022}, author = {Wang, Y and Tang, J and Lv, Q and Tan, Y and Dong, X and Liu, H and Zhao, N and He, Z and Kou, Y and Tan, Y and Liu, XA and Wang, L and Liu, YY and Dai, L}, title = {Establishment and resilience of transplanted gut microbiota in aged mice.}, journal = {iScience}, volume = {25}, number = {1}, pages = {103654}, pmid = {35024588}, issn = {2589-0042}, support = {R01 AI141529/AI/NIAID NIH HHS/United States ; }, abstract = {The maintenance of healthy and resilient gut microbiota is critical for the life quality and healthspan of the elderly. Fecal microbiota transplantation (FMT) has been increasingly used to restore healthy gut microbiota. We systemically studied the establishment and resilience of transplanted microbiota after autologous versus heterologous FMT in aged recipients. Gut microbiota of aged mice (20 months old) failed to restore their original diversity and composition over 8 weeks via spontaneous recovery after antibiotics treatment; in contrast, FMT using either autologous or heterologous (2 months old from a different vendor) donors facilitated the recovery successfully, established donor-like microbiota states, and affected host gene expression profile. Furthermore, the transplanted microbiota established by heterologous FMT is not resilient during chemical-induced colonic inflammation, in contrast to that of autologous FMT. Our findings highlighted the need to monitor the long-term stability of transplanted gut microbiota and to perform multiple FMT when necessary.}, }
@article {pmid35023946, year = {2022}, author = {Azimirad, M and Jo, Y and Kim, MS and Jeong, M and Shahrokh, S and Asadzadeh Aghdaei, H and Zali, MR and Lee, S and Yadegar, A and Shin, JH}, title = {Alterations and Prediction of Functional Profiles of Gut Microbiota After Fecal Microbiota Transplantation for Iranian Recurrent Clostridioides difficile Infection with Underlying Inflammatory Bowel Disease: A Pilot Study.}, journal = {Journal of inflammation research}, volume = {15}, number = {}, pages = {105-116}, pmid = {35023946}, issn = {1178-7031}, abstract = {BACKGROUND AND PURPOSE: Fecal microbiota transplantation (FMT) has emerged for the therapeutic treatment of recurrent Clostridioides difficile infection (rCDI) with concurrent inflammatory bowel disease (IBD). As the first Iranian population cohort, we examined how gut microbiota and their functional profiles change in Iranian rCDI patients with underlying IBD before and after FMT.<br><br>PATIENTS AND METHODS: FMT was performed to eight IBD patients via colonoscopy. Profiles of gut microbiota from donors and recipients were investigated using 16S rRNA gene sequence analysis.<br><br>RESULTS: Patients experienced no IBD flare-ups or other adverse effects, and all recovered to full health. Moreover, all rCDI patients lacked the Bacteroidetes present in donor samples. After FMT, the proportion of Bacteroidetes increased until a normal range was achieved. More specifically, the relative abundance of Prevotella was found to increase significantly following FMT. Prevotella was also found to correlate negatively with inflammation metrics, suggesting that Prevotella may be a key factor for resolving CDI and IBD. Gut microbiota diversity was found to increase following FMT, while dysbiosis decreased. However, the similarity of microbial communities of host and recipients did not increase, and wide variation in the extent of donor stool engraftment indicated that the gut bacterial communities of recipients do not shift towards those of donors.<br><br>CONCLUSION: FMT leads to significant alterations of the community structure of gut bacteria in rCDI patients with IBD. The change in relative abundance of Proteobacteria and bacterial diversity indicated that FMT promotes recovery from intestinal permeability and inflammation in rCDI patients. Moreover, strong negative correlation between Prevotella and inflammation index, and decreased dysbiosis index advocate that the improvement of CDI is possibly due to gut microbiome alteration. Collectively, our findings show that FMT would be a promising therapy to help reprogram the gut microbiome of Iranian rCDI patients with IBD.}, }
@article {pmid35021112, year = {2022}, author = {Salavati Schmitz, S}, title = {Observational Study of Small Animal Practitioners' Awareness, Clinical Practice and Experience With Fecal Microbiota Transplantation in Dogs.}, journal = {Topics in companion animal medicine}, volume = {47}, number = {}, pages = {100630}, doi = {10.1016/j.tcam.2022.100630}, pmid = {35021112}, issn = {1946-9837}, mesh = {Animals ; Diarrhea/veterinary ; *Dog Diseases/therapy ; Dogs ; Fecal Microbiota Transplantation/methods/veterinary ; Feces ; *Gastrointestinal Diseases/veterinary ; *Parvoviridae Infections/veterinary ; Treatment Outcome ; }, abstract = {To assess small animal practitioner's awareness of the relatively novel procedure of fecal microbiota transplantation (FMT) in dogs and their practices, indications, experience and assessment of outcome of this in canine patients. An anonymous online questionnaire was distributed to practitioners in the UK and around the world, assessing demographics of respondents, their selection criteria for donors, their operating procedures and indications when performing FMT in dogs, as well as the observed outcomes. Analysis of results was descriptive. Data based on 155 responses from 13 different countries, 40% from primary care practices and 60% from referral hospitals, were analyzed. The majority of respondents (71%) had never performed FMT. For the remaining, main indications were chronic enteropathy (64%) and parvovirus infection (21%), followed by other types of acute diarrhea (15%). The most common mode of administration was via enema (79%) or endoscopically (55%), using fresh (76%) or frozen (46%) preparations mixed with saline and/or water, while the amount administered was extremely variable. Median storage time of FMT was 90 days (range 1-180 days). 67% of participants routinely administer FMT more than once. Clinical response was mixed to good, with rare adverse events (n = 4). A total of 25 respondents (21.7%) wanted to start using FMT, while 45 (29%) wanted to continue or increase FMT administration for various gastrointestinal conditions. In conclusion, an administration of FMT to dogs is currently rare amongst small animal practitioners, but generally follow current recommendations. Urgent consensus regarding donor selection and FMT application procedures for dogs is required.}, }
@article {pmid35019780, year = {2022}, author = {Liu, L and Kirst, ME and Zhao, L and Li, E and Wang, GP}, title = {Microbiome Resilience despite a Profound Loss of Minority Microbiota following Clindamycin Challenge in Humanized Gnotobiotic Mice.}, journal = {Microbiology spectrum}, volume = {10}, number = {1}, pages = {e0196021}, pmid = {35019780}, issn = {2165-0497}, support = {R21 AI150250/AI/NIAID NIH HHS/United States ; R21 MH106983/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/drug effects/genetics ; Clindamycin/*pharmacology/therapeutic use ; Disease Models, Animal ; Dysbiosis ; Feces/microbiology ; Gastrointestinal Diseases/drug therapy ; Gastrointestinal Microbiome/*drug effects/genetics ; Germ-Free Life/*drug effects ; Humans ; Male ; Mice ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Antibiotics are known to induce gut dysbiosis and increase the risk of antibiotic resistance. While antibiotic exposure is a known risk factor leading to compromised colonization resistance against enteric pathogens such as Clostridioides difficile, the extent and consequences of antibiotic perturbation on the human gut microbiome remain poorly understood. Human studies on impacts of antibiotics are complicated by the tremendous variability of gut microbiome among individuals, even between identical twins. Furthermore, antibiotic challenge experiments cannot be replicated in human subjects for a given gut microbiome. Here, we transplanted feces from three unrelated human donors into groups of identical germfree (GF) Swiss-Webster mice, and examined the temporal responses of the transplanted microbiome to oral clindamycin challenge in gnotobiotic isolators over 7 weeks. Analysis of 177 longitudinal fecal samples revealed that 59% to 81% of human microbiota established a stable configuration rapidly and stably in GF mice. Microbiome responses to clindamycin challenge was highly reproducible and microbiome-dependent. A short course of clindamycin was sufficient to induce a profound loss (∼one third) of the microbiota by disproportionally eliminating minority members of the transplanted microbiota. However, it was inadequate to disrupt the global microbial community structure or function, which rebounded rapidly to resemble its pre-treatment state after clindamycin discontinuation. Furthermore, the response of individual microbes was community-dependent. Taken together, these results suggest that the overall gut microbiome structure is resilient to antibiotic perturbation, the functional consequences of which warrant further investigation. IMPORTANCE Antibiotics cause imbalance of gut microbiota, which in turn increase our susceptibility to gastrointestinal infections. However, how antibiotics disrupt gut bacterial communities is not well understood, and exposing healthy volunteers to unnecessary antibiotics for research purposes carries clinical and ethical concerns. In this study, we used genetically identical mice transplanted with the same human gut microbiota to control for both genetic and environmental variables. We found that a short course of oral clindamycin was sufficient to eliminate one third of the gut bacteria by disproportionally eliminating minority members of the transplanted microbiota, but it was inadequate to disrupt the overall microbial community structure and function, which rebounded rapidly to its pre-treatment state. These results suggest that gut microbiome is highly resilient to antibiotic challenge and degradation of the human gut ecosystem may require repeated or prolonged antibiotic exposure.}, }
@article {pmid35017486, year = {2022}, author = {Hu, H and Shao, W and Liu, Q and Liu, N and Wang, Q and Xu, J and Zhang, X and Weng, Z and Lu, Q and Jiao, L and Chen, C and Sun, H and Jiang, Z and Zhang, X and Gu, A}, title = {Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {252}, pmid = {35017486}, issn = {2041-1723}, mesh = {Animals ; Bile/metabolism ; Bile Acids and Salts/*metabolism ; Cholelithiasis ; Cholesterol/*biosynthesis ; Cholesterol 7-alpha-Hydroxylase/genetics/metabolism ; Desulfovibrionales/physiology ; Digestion/*physiology ; Feces/microbiology ; Gallstones/*metabolism ; Gastrointestinal Microbiome/*physiology ; Intestinal Absorption ; Lipid Metabolism ; Lipogenesis ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; }, abstract = {Cholesterol gallstone disease is a worldwide common disease. Cholesterol supersaturation in gallbladder bile is the prerequisite for its pathogenesis, while the mechanism is not completely understood. In this study, we find enrichment of gut microbiota (especially Desulfovibrionales) in patients with gallstone disease. Fecal transplantation of gut microbiota from gallstone patients to gallstone-resistant strain of mice can induce gallstone formation. Carrying Desulfovibrionales is associated with enhanced cecal secondary bile acids production and increase of bile acid hydrophobicity facilitating intestinal cholesterol absorption. Meanwhile, the metabolic product of Desulfovibrionales, H2S increase and is shown to induce hepatic FXR and inhibit CYP7A1 expression. Mice carrying Desulfovibrionales present induction of hepatic expression of cholesterol transporters Abcg5/g8 to promote biliary secretion of cholesterol as well. Our study demonstrates the role of gut microbiota, Desulfovibrionales, as an environmental regulator contributing to gallstone formation through its influence on bile acid and cholesterol metabolism.}, }
@article {pmid35017199, year = {2022}, author = {Chen, C and Liao, J and Xia, Y and Liu, X and Jones, R and Haran, J and McCormick, B and Sampson, TR and Alam, A and Ye, K}, title = {Gut microbiota regulate Alzheimer's disease pathologies and cognitive disorders via PUFA-associated neuroinflammation.}, journal = {Gut}, volume = {71}, number = {11}, pages = {2233-2252}, pmid = {35017199}, issn = {1468-3288}, support = {P30 AG066511/AG/NIA NIH HHS/United States ; R01 AG065177/AG/NIA NIH HHS/United States ; RF1 AG067483/AG/NIA NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; K23 AG057790/AG/NIA NIH HHS/United States ; R56 DK136728/DK/NIDDK NIH HHS/United States ; K01 DK114391/DK/NIDDK NIH HHS/United States ; P20 GM130456/GM/NIGMS NIH HHS/United States ; }, mesh = {*Alzheimer Disease/metabolism ; Animals ; Cognition ; Disease Models, Animal ; Dysbiosis ; Fatty Acids, Unsaturated ; *Gastrointestinal Microbiome/physiology ; Humans ; Inflammation/metabolism ; Insulin-Like Growth Factor I ; *Insulins ; Mice ; Neuroinflammatory Diseases ; Plaque, Amyloid/pathology ; RNA, Ribosomal, 16S ; }, abstract = {OBJECTIVE: This study is to investigate the role of gut dysbiosis in triggering inflammation in the brain and its contribution to Alzheimer's disease (AD) pathogenesis.<br><br>DESIGN: We analysed the gut microbiota composition of 3&#xd7;Tg mice in an age-dependent manner. We generated germ-free 3&#xd7;Tg mice and recolonisation of germ-free 3&#xd7;Tg mice with fecal samples from both patients with AD and age-matched healthy donors.<br><br>RESULTS: Microbial 16S rRNA sequencing revealed Bacteroides enrichment. We found a prominent reduction of cerebral amyloid-&#x3b2; plaques and neurofibrillary tangles pathology in germ-free 3&#xd7;Tg mice as compared with specific-pathogen-free mice. And hippocampal RNAseq showed that inflammatory pathway and insulin/IGF-1 signalling in 3&#xd7;Tg mice brain are aberrantly altered in the absence of gut microbiota. Poly-unsaturated fatty acid metabolites identified by metabolomic analysis, and their oxidative enzymes were selectively elevated, corresponding with microglia activation and inflammation. AD patients' gut microbiome exacerbated AD pathologies in 3&#xd7;Tg mice, associated with C/EBP&#x3b2;/asparagine endopeptidase pathway activation and cognitive dysfunctions compared with healthy donors' microbiota transplants.<br><br>CONCLUSIONS: These findings support that a complex gut microbiome is required for behavioural defects, microglia activation and AD pathologies, the gut microbiome contributes to pathologies in an AD mouse model and that dysbiosis of the human microbiome might be a risk factor for AD.}, }
@article {pmid35014601, year = {2022}, author = {Singh, P and Alm, EJ and Kelley, JM and Cheng, V and Smith, M and Kassam, Z and Nee, J and Iturrino, J and Lembo, A}, title = {Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2020067}, pmid = {35014601}, issn = {1949-0984}, support = {K23 DK129327/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacteria/classification/drug effects/genetics/isolation &amp; purification ; Ciprofloxacin/administration &amp; dosage ; Combined Modality Therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/drug effects ; Humans ; Irritable Bowel Syndrome/drug therapy/microbiology/*therapy ; Male ; Metronidazole/administration &amp; dosage ; Middle Aged ; Quality of Life ; Rifaximin/administration &amp; dosage ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is an attractive strategy to correct microbial dysbiosis in diarrhea-predominant irritable bowel syndrome (IBS-D). Although the mechanism of FMT is thought to be bacterial engraftment, the best approach to achieve engraftment after FMT in IBS-D (and other diseases) is not clear. We evaluated the effect of FMT (with or without pretreatment with antibiotics) on gut microbiome and symptoms in patients with IBS-D. In this randomized, placebo-controlled, single-center study, 44 patients with IBS-D with a least moderate severity (IBS severity scoring system, i.e., IBS-SSS, ≥175) were randomly assigned to one of four groups: single-dose oral FMT alone, single-dose oral FMT following a 7-day pretreatment course of Ciprofloxacin and Metronidazole (CM-FMT) or Rifaximin (R-FMT), or Placebo FMT. Primary endpoint was engraftment post-FMT and secondary endpoints were changes in IBS-SSS, and IBS-quality of life (IBS-QOL) at week 10. Median engraftment was significantly different among the three FMT groups (P = .013). Engraftment post-FMT was significantly higher in the FMT alone arm (15.5%) compared to that in R-FMT group (5%, P = .04) and CM-FMT group (2.4%, P = .002). The mean change in IBS-SSS and IBS-QOL from baseline were not significantly different among the four groups or between the three FMT groups combined vs. placebo at week 10. In summary, antibiotic pretreatment significantly reduced bacterial engraftment after FMT in patients with IBS-D.}, }
@article {pmid35013245, year = {2022}, author = {Jee, JJ and Yang, L and Shivakumar, P and Xu, PP and Mourya, R and Thanekar, U and Yu, P and Zhu, Y and Pan, Y and Wang, H and Duan, X and Ye, Y and Wang, B and Jin, Z and Liu, Y and Cao, Z and Watanabe-Chailland, M and Romick-Rosendale, LE and Wagner, M and Fei, L and Luo, Z and Ollberding, NJ and Tang, ST and Bezerra, JA}, title = {Maternal regulation of biliary disease in neonates via gut microbial metabolites.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {18}, pmid = {35013245}, issn = {2041-1723}, support = {P30 DK078392/DK/NIDDK NIH HHS/United States ; R01 DK064008/DK/NIDDK NIH HHS/United States ; R01 DK083781/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn ; Bile Ducts/metabolism ; Biliary Atresia/*immunology/*therapy ; Cholestasis/*metabolism ; Disease Models, Animal ; Epithelial Cells/metabolism ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; Inflammation/metabolism ; Killer Cells, Natural/immunology ; Liver/injuries/metabolism/pathology ; Mice ; Mice, Inbred BALB C ; Pregnancy ; }, abstract = {Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding butyrate to pregnant mice influences the newborn's susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells.}, }
@article {pmid35011199, year = {2021}, author = {Chen, S and Luo, S and Yan, C}, title = {Gut Microbiota Implications for Health and Welfare in Farm Animals: A Review.}, journal = {Animals : an open access journal from MDPI}, volume = {12}, number = {1}, pages = {}, pmid = {35011199}, issn = {2076-2615}, support = {2019A1515110598//the Joint Fund of Basic and Applied Basic Research Fund of Guangdong Province/ ; 2019B030301010//the Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding/ ; }, abstract = {In the past few decades, farm animal health and welfare have been paid increasing concern worldwide. Farm animal health and welfare are generally assessed by the measurements of physical health, immune response, behavior, and physiological indicators. The gut microbiota has been reported to have a great influence on host phenotypes, possibly via the immune processes, neural functions, and endocrine pathways, thereby influencing host phenotypes. However, there are few reviews regarding farm animals' health and welfare status concerning the gut microbiota. In this point of view, (1) we reviewed recent studies showing that gut microbiota (higher alpha diversity, beneficial composition, and positive functions) effectively influenced health characteristics, immunity, behaviors, and stress response in farm animals (such as pigs, chickens, and cows), which would provide a novel approach to measure and evaluate the health status and welfare of farm animals. In addition, fecal microbiota transplantation (FMT) as one of the methods can modulate the recipient individual's gut microbiota to realize the expected phenotype. Further, (2) we highlighted the application of FMT on the improvement of the production performance, the reduction in disease and abnormal behavior, as well as the attenuation of stress in farm animals. It is concluded that the gut microbiota can be scientifically used to assess and improve the welfare of farm animals. Moreover, FMT may be a helpful strategy to reduce abnormal behavior and improve stress adaption, as well as the treatment of disease for farm animals. This review suggests that gut microbiota is a promising field to evaluate and improve animal welfare.}, }
@article {pmid35011044, year = {2021}, author = {Iatcu, CO and Steen, A and Covasa, M}, title = {Gut Microbiota and Complications of Type-2 Diabetes.}, journal = {Nutrients}, volume = {14}, number = {1}, pages = {}, pmid = {35011044}, issn = {2072-6643}, support = {120/16.09.2016.//European Regional Development Fund through Competitiveness Operational Program/ ; }, mesh = {Amino Acids ; Animals ; Chromium ; Diabetes Mellitus, Type 2/etiology/*microbiology/*therapy ; Diabetic Nephropathies/etiology/therapy ; Diabetic Retinopathy/etiology/therapy ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Insulin Resistance ; Nicotinic Acids ; Patient Acuity ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; Synbiotics/administration &amp; dosage ; }, abstract = {The gut microbiota has been linked to the emergence of obesity, metabolic syndrome and the onset of type 2 diabetes through decreased glucose tolerance and insulin resistance. Uncontrolled diabetes can lead to serious health consequences such as impaired kidney function, blindness, stroke, myocardial infarction and lower limb amputation. Despite a variety of treatments currently available, cases of diabetes and resulting complications are on the rise. One promising new approach to diabetes focuses on modulating the gut microbiota with probiotics, prebiotics, synbiotics and fecal microbial transplantation. Differences in gut microbiota composition have been observed in preclinical animal models as well as patients with type 2 diabetes and complications such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, cerebrovascular disease, coronary heart disease and peripheral artery disease compared to healthy controls. Severity of gut microbiota dysbiosis was associated with disease severity and restoration with probiotic administration in animal models and human patients has been associated with improvement of symptoms and disease progression. Characterizing the gut microbiota dysbiosis in different diseases and determining a causal relationship between the gut microbiota and disease can be beneficial in formulating therapeutic interventions for type 2 diabetes and associated complications. In this review, we present the most important findings regarding the role of the gut microbiota in type 2 diabetes and chronic complications as well as their underlying mechanisms.}, }
@article {pmid35010223, year = {2021}, author = {Liu, P and Zhou, W and Xu, W and Peng, Y and Yan, Y and Lu, L and Mi, J and Zeng, X and Cao, Y}, title = {The Main Anthocyanin Monomer from Lycium ruthenicum Murray Fruit Mediates Obesity via Modulating the Gut Microbiota and Improving the Intestinal Barrier.}, journal = {Foods (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {35010223}, issn = {2304-8158}, support = {2019BFG02026//Research and Development Project funded by Ningxia Hui Autonomous Region of China/ ; PAPD//Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, abstract = {Anthocyanins have been shown to exert certain antiobesity properties, but the specific relationship between anthocyanin-induced beneficial effects and the gut microbiota remains unclear. Petunidin-3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(β-D-glucopyranoside) (P3G) is the main anthocyanin monomer from the fruit of Lycium ruthenicum Murray. Therefore, in this study, we investigated the antiobesity and remodeling effects of P3G on gut microbiota through a high-fat diet (HFD)-induced obesity mouse model and a fecal microbiota transplantation experiment. P3G was found to reduce body weight gain, fat accumulation, and liver steatosis in HFD-induced obese mice. Moreover, supplementation with P3G alleviated the HFD-induced imbalance in gut microbiota composition, and transferring the P3G-regulated gut microbiota to recipient mice provided comparable protection against obesity. This is the first time evidence is provided that P3G has an antiobesity effect by changing the intestinal microbiota. Our present data highlight a link between P3G intervention and enhancement in gut barrier integrity. This may be a promising option for obesity prevention.}, }
@article {pmid35008915, year = {2022}, author = {Sevcikova, A and Izoldova, N and Stevurkova, V and Kasperova, B and Chovanec, M and Ciernikova, S and Mego, M}, title = {The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, pmid = {35008915}, issn = {1422-0067}, support = {APVV-19-0411, APVV-20-0158//Slovak Research and Development Agency/ ; 1/0327/19, 2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology/*therapeutic use ; Clinical Trials as Topic ; *Drug Resistance, Neoplasm/drug effects ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Immunotherapy ; Neoplasms/*drug therapy/*microbiology ; }, abstract = {Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.}, }
@article {pmid35007789, year = {2022}, author = {Gueddouri, D and Caüzac, M and Fauveau, V and Benhamed, F and Charifi, W and Beaudoin, L and Rouland, M and Sicherre, F and Lehuen, A and Postic, C and Boudry, G and Burnol, AF and Guilmeau, S}, title = {Insulin resistance per se drives early and reversible dysbiosis-mediated gut barrier impairment and bactericidal dysfunction.}, journal = {Molecular metabolism}, volume = {57}, number = {}, pages = {101438}, pmid = {35007789}, issn = {2212-8778}, mesh = {Animals ; *Diabetes Mellitus, Experimental ; Dysbiosis/metabolism/microbiology ; *Gastrointestinal Microbiome/physiology ; Inflammation/metabolism ; *Insulin Resistance ; Mice ; }, abstract = {OBJECTIVE: A common feature of metabolic diseases is their association with chronic low-grade inflammation. While enhanced gut permeability and systemic bacterial endotoxin translocation have been suggested as key players of this metaflammation, the mechanistic bases underlying these features upon the diabesity cascade remain partly understood.<br><br>METHODS: Here, we show in mice that, independently of obesity, the induction of acute and global insulin resistance and associated hyperglycemia, upon treatment with an insulin receptor (IR) antagonist (S961), elicits gut hyperpermeability without triggering systemic inflammatory response.<br><br>RESULTS: Of note, S961-treated diabetic mice display major defects of gut barrier epithelial functions, such as increased epithelial paracellular permeability and impaired cell-cell junction integrity. We also observed in these mice the early onset of a severe gut dysbiosis, as characterized by the bloom of pro-inflammatory Proteobacteria, and the later collapse of Paneth cells antimicrobial defense. Interestingly, S961 treatment discontinuation is sufficient to promptly restore both the gut microbial balance and the intestinal barrier integrity. Moreover, fecal transplant approaches further confirm that S961-mediated dybiosis contributes at least partly to the disruption of the gut selective epithelial permeability upon diabetic states.<br><br>CONCLUSIONS: Together, our results highlight that insulin signaling is an indispensable gatekeeper of intestinal barrier integrity, acting as a safeguard against microbial imbalance and acute infections by enteropathogens.}, }
@article {pmid35004750, year = {2021}, author = {Wang, H and Wang, H and Sun, Y and Ren, Z and Zhu, W and Li, A and Cui, G}, title = {Potential Associations Between Microbiome and COVID-19.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {785496}, pmid = {35004750}, issn = {2296-858X}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis. The disease is characterized by strong infectivity, high morbidity, and high mortality. It is still spreading in some countries. Microbiota and their metabolites affect human physiological health and diseases by participating in host digestion and nutrition, promoting metabolic function, and regulating the immune system. Studies have shown that human microecology is associated with many diseases, including COVID-19. In this research, we first reviewed the microbial characteristics of COVID-19 from the aspects of gut microbiome, lung microbime, and oral microbiome. We found that significant changes take place in both the gut microbiome and airway microbiome in patients with COVID-19 and are characterized by an increase in conditional pathogenic bacteria and a decrease in beneficial bacteria. Then, we summarized the possible microecological mechanisms involved in the progression of COVID-19. Intestinal microecological disorders in individuals may be involved in the occurrence and development of COVID-19 in the host through interaction with ACE2, mitochondria, and the lung-gut axis. In addition, fecal bacteria transplantation (FMT), prebiotics, and probiotics may play a positive role in the treatment of COVID-19 and reduce the fatal consequences of the disease.}, }
@article {pmid35003127, year = {2021}, author = {Yuan, B and Lu, XJ and Wu, Q}, title = {Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {800796}, pmid = {35003127}, issn = {1664-3224}, mesh = {Animals ; *Brain Injuries, Traumatic/immunology/microbiology ; Brain-Gut Axis/*immunology ; Gastrointestinal Microbiome/*immunology ; Humans ; Neuroimmunomodulation/immunology ; Neuroinflammatory Diseases/immunology/microbiology ; *Spinal Cord Injuries/immunology/microbiology ; *Stroke/immunology/microbiology ; }, abstract = {Acute central nervous system (CNS) injuries, including stroke, traumatic brain injury (TBI), and spinal cord injury (SCI), are the common causes of death or lifelong disabilities. Research into the role of the gut microbiota in modulating CNS function has been rapidly increasing in the past few decades, particularly in animal models. Growing preclinical and clinical evidence suggests that gut microbiota is involved in the modulation of multiple cellular and molecular mechanisms fundamental to the progression of acute CNS injury-induced pathophysiological processes. The altered composition of gut microbiota after acute CNS injury damages the equilibrium of the bidirectional gut-brain axis, aggravating secondary brain injury, cognitive impairments, and motor dysfunctions, which leads to poor prognosis by triggering pro-inflammatory responses in both peripheral circulation and CNS. This review summarizes the studies concerning gut microbiota and acute CNS injuries. Experimental models identify a bidirectional communication between the gut and CNS in post-injury gut dysbiosis, intestinal lymphatic tissue-mediated neuroinflammation, and bacterial-metabolite-associated neurotransmission. Additionally, fecal microbiota transplantation, probiotics, and prebiotics manipulating the gut microbiota can be used as effective therapeutic agents to alleviate secondary brain injury and facilitate functional outcomes. The role of gut microbiota in acute CNS injury would be an exciting frontier in clinical and experimental medicine.}, }
@article {pmid35001039, year = {2022}, author = {Strisciuglio, C and Banasiuk, M and Salvatore, S and Borrelli, O and Staiano, A and Van Wijk, M and Vandenplas, Y and Benninga, MA and Thapar, N}, title = {Anorectal Manometry in Children: The Update on the Indications and the Protocol of the Procedure.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {74}, number = {4}, pages = {440-445}, pmid = {35001039}, issn = {1536-4801}, mesh = {Anal Canal ; Child ; *Fecal Incontinence/diagnosis/etiology ; Humans ; Manometry/methods ; *Rectal Diseases/complications ; Rectum ; Review Literature as Topic ; }, abstract = {Anorectal disorders are common in children. They are related to structural and/or functional abnormalities of the anorectum or pelvic floor with a variety of symptoms. Therefore, diagnostic tests to evaluate anorectal function can help to better understand the underlying pathophysiology and aetiology as well as facilitate patient management. During the past decades, substantial efforts have been made to improve anorectal function testing; however, more advanced investigations might lead to difficulties in interpretation. Additionally, a great diversity of equipment and protocols are used among centres, which may lead to heterogeneous interpretation of results. More studies to standardize methods of testing and validate reference values are strongly recommended in children. This review updates on the current indications and the protocol of anorectal manometry.}, }
@article {pmid35000023, year = {2022}, author = {Suchman, K and Luo, Y and Grinspan, A}, title = {Fecal Microbiota Transplant for Clostridioides Difficile Infection Is Safe and Efficacious in an Immunocompromised Cohort.}, journal = {Digestive diseases and sciences}, volume = {67}, number = {10}, pages = {4866-4873}, pmid = {35000023}, issn = {1573-2568}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Biological Products ; Child ; *Clostridioides difficile ; *Clostridium Infections/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; Female ; Follow-Up Studies ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/adverse effects ; *Inflammatory Bowel Diseases/etiology/therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Recurrence ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Immunocompromised patients are particularly vulnerable to Clostridioides difficile infection (CDI), hospitalizations and recurrences. Studies have shown that fecal microbiota transplant (FMT) is safe and effective in immunocompromised patients.<br><br>AIMS: To examine the outcomes of FMT for CDI in a diverse cohort of immunocompromised patients stratified by medication class.<br><br>METHODS: We performed a retrospective, long-term follow-up study of FMT in immunocompromised patients, including those undergoing chemotherapy, with inflammatory bowel disease (IBD) on immunomodulators, prior solid organ transplant on immunosuppressants, on chronic steroids 20&#xa0;mg/day or higher for a minimum of three months, or HIV positive. Primary outcomes included adjusted primary cure rate within 8&#xa0;weeks, as well as rates of non-response, recurrences, relapses and adverse events. Secondary outcomes included adjusted overall cure rate. Primary cure rate was defined as patients not requiring repeat CDI treatment within 8&#xa0;weeks after index FMT, and overall cure rate was defined as resolution of CDI symptoms after index FMT or second FMT.<br><br>RESULTS: Our cohort included 77 immunosuppressed patients (53.2% female, median age 39.1&#xa0;years, range 7-95&#xa0;years). The majority of our cohort were IBD patients on biologics (62.3%). Adjusting for colectomies and deaths, our primary and overall cure rates were 85.1% and 86.5%, respectively. Twelve patients received FMT for severe or fulminant CDI with a 3-month survival rate of 91.7%. 11.7% of patients experienced serious adverse events following FMT.<br><br>CONCLUSIONS: Our study supports the efficacy and safety of FMT in immunocompromised patients, though future research is needed to further ascertain the potential effects of immunosuppression on FMT outcomes.}, }
@article {pmid34992678, year = {2021}, author = {Sandhu, A and Chopra, T}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile, safety, and pitfalls.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211053105}, pmid = {34992678}, issn = {1756-283X}, abstract = {Clostridioides difficile infection (CDI) is one of the leading causes of hospital-acquired infection attributing to substantial morbidity, mortality, and healthcare cost. Recurrent CDI (rCDI) is common and occurs after effective treatment of first episode. Treatment of rCDI is based on accurate diagnoses, due to difficulty in distinguishing between colonization of C. difficile spores or CDI; coronavirus disease 2019 (COVID-19) added to the complexity of diagnoses as both entities can co-occur. It is difficult to eradicate rCDI, and there remains a critical gap regarding treatment of rCDI. The treatment goal of rCDI is to reestablish normal microbiota. Fecal microbiota transplantation (FMT) is suggested as a treatment for second episode of rCDI. Based on the collective evidence of all randomized controlled trials, FMT was reported more efficacious compared with vancomycin or fidaxomicin; however, these trials had limited number of patients and all patients were pre-treated with vancomycin prior to FMT. Furthermore, when comparing various routes of instillation and types of preparation of fecal microbiota, no difference was observed in cure rate. Despite the success rate of FMT, there remains a concern for transmission of infectious agents, such as Gram negative bacteremia or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adverse events (diarrhea and abdominal pain), and reports of new diagnoses (inflammatory bowel disease, weight gain and irritable bowel syndrome). To lessen the risk of transmissible infections, donor screening should be performed, which includes screening for medical comorbidities and infectious pathogens in blood and feces. Scheduling complexities and reimbursement places an additional roadblock for using FMT. Microbiome-based therapies are being developed to eliminate the logistical challenges related to FMT. Large prospective and placebo-controlled studies are needed to evaluate the efficacy and long-term safety of FMT, so its use can be justified in clinical practice.}, }
@article {pmid34992606, year = {2021}, author = {Lai, J and Zhang, P and Jiang, J and Mou, T and Li, Y and Xi, C and Wu, L and Gao, X and Zhang, D and Chen, Y and Huang, H and Li, H and Cai, X and Li, M and Zheng, P and Hu, S}, title = {New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {789647}, pmid = {34992606}, issn = {1664-3224}, mesh = {Adolescent ; Adult ; Animals ; Bipolar Disorder/blood/*immunology/microbiology/pathology ; Brain-Gut Axis/*immunology ; Case-Control Studies ; Cell Line ; Cytokines/analysis/*metabolism ; Depression/blood/*immunology/microbiology/pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Healthy Volunteers ; Hippocampus/immunology/metabolism/pathology ; Humans ; Lipopolysaccharides/immunology ; Male ; Mice ; Microglia/immunology/metabolism ; Neurons/immunology/metabolism ; Prefrontal Cortex/immunology/metabolism/pathology ; Primary Cell Culture ; Young Adult ; }, abstract = {Tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1) is a robust risk gene of bipolar disorder (BD). However, little is known on the role of TRANK1 in the pathogenesis of BD and whether the gut microbiota is capable of regulating TRANK1 expression. In this study, we first investigated the serum mRNA level of TRANK1 in medication-free patients with a depressive episode of BD, then a mice model was constructed by fecal microbiota transplantation (FMT) to explore the effects of gut microbiota on brain TRANK1 expression and neuroinflammation, which was further verified by in vitro Lipopolysaccharide (LPS) treatment in BV-2 microglial cells and neurons. 22 patients with a depressive episode and 28 healthy individuals were recruited. Serum level of TRANK1 mRNA was higher in depressed patients than that of healthy controls. Mice harboring 'BD microbiota' following FMT presented depression-like phenotype. mRNA levels of inflammatory cytokines and TRANK1 were elevated in mice hippocampus and prefrontal cortex. In vitro, LPS treatment activated the secretion of pro-inflammatory factors in BV-2 cells, which was capable of upregulating the neuronal expression of TRANK1 mRNA. Moreover, primary cortical neurons transfected with plasmid Cytomegalovirus DNA (pcDNA3.1(+)) vector encoding human TRANK1 showed decreased dendritic spine density. Together, these findings add new evidence to the microbiota-gut-brain regulation in BD, indicating that microbiota is possibly involved in the neuropathogenesis of BD by modulating the expression of TRANK1.}, }
@article {pmid34992261, year = {2022}, author = {Sorbara, MT and Pamer, EG}, title = {Microbiome-based therapeutics.}, journal = {Nature reviews. Microbiology}, volume = {20}, number = {6}, pages = {365-380}, pmid = {34992261}, issn = {1740-1534}, support = {R01 AI095706/AI/NIAID NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; FRN 152527//CIHR/Canada ; }, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Health Promotion ; Humans ; *Microbiota ; }, abstract = {Symbiotic microorganisms inhabiting the gastrointestinal tract promote health by decreasing susceptibility to infection and enhancing resistance to a range of diseases. In this Review, we discuss our increasing understanding of the impact of the microbiome on the mammalian host and recent efforts to culture and characterize intestinal symbiotic microorganisms that produce or modify metabolites that impact disease pathology. Manipulation of the intestinal microbiome has great potential to reduce the incidence and/or severity of a wide range of human conditions and diseases, and the biomedical research community now faces the challenge of translating our understanding of the microbiome into beneficial medical therapies. Our increasing understanding of symbiotic microbial species and the application of ecological principles and machine learning are providing exciting opportunities for microbiome-based therapeutics to progress from faecal microbiota transplantation to the administration of precisely defined and clinically validated symbiotic microbial consortia that optimize disease resistance.}, }
@article {pmid34991182, year = {2022}, author = {Tolbert, MK and Murphy, M and Gaylord, L and Witzel-Rollins, A}, title = {Dietary management of chronic enteropathy in dogs.}, journal = {The Journal of small animal practice}, volume = {63}, number = {6}, pages = {425-434}, doi = {10.1111/jsap.13471}, pmid = {34991182}, issn = {1748-5827}, mesh = {Animals ; *Dog Diseases/diagnosis/therapy ; Dogs ; *Inflammatory Bowel Diseases/veterinary ; }, abstract = {Chronic idiopathic enteropathy is a clinical condition defined by the exclusion of infectious, metabolic or neoplastic causes of gastrointestinal signs and is categorised by a response to treatment including management with diet change, immunosuppressant medication or interventions that directly target the microbiome (e.g. antibiotics, faecal transplantation or probiotics). Animals that fail these therapies are categorised as non-responsive or refractory chronic idiopathic enteropathy. This specific categorisation implies that nutritional intervention is only needed for a subset of patients with enteropathy. However, often dogs with chronic idiopathic enteropathy are malnourished, have nutrient malabsorption or have gastrointestinal inflammation that occurs as a result of a breakdown in tolerance to luminal antigens including microorganism or dietary components. Thus, all dogs with chronic idiopathic enteropathy benefit from a nutritional assessment and targeted nutritional intervention. Among dogs presenting for chronic idiopathic enteropathy, the response rate to diet alone is roughly 50% in the referral population giving the impression that the overall response could be even higher especially when more than one nutritional intervention is attempted and strict adherence is maintained. The objectives of this review article are to outline the nutritional approach to a dog with chronic idiopathic enteropathy, including the nutritional assessment, and to highlight areas for nutritional intervention.}, }
@article {pmid34990844, year = {2022}, author = {Aaldijk, E and Vermeiren, Y}, title = {The role of serotonin within the microbiota-gut-brain axis in the development of Alzheimer's disease: A narrative review.}, journal = {Ageing research reviews}, volume = {75}, number = {}, pages = {101556}, doi = {10.1016/j.arr.2021.101556}, pmid = {34990844}, issn = {1872-9649}, mesh = {*Alzheimer Disease/pathology ; Animals ; Brain/pathology ; Brain-Gut Axis ; *Gastrointestinal Microbiome ; Humans ; Mice ; Serotonin ; }, abstract = {Alzheimer's disease (AD) is the most common cause of dementia, accounting for more than 50 million patients worldwide. Current evidence suggests the exact mechanism behind this devastating disease to be of multifactorial origin, which seriously complicates the quest for an effective disease-modifying therapy, as well as impedes the search for strategic preventative measures. Of interest, preclinical studies point to serotonergic alterations, either induced via selective serotonin reuptake inhibitors or serotonin receptor (ant)agonists, in mitigating AD brain neuropathology next to its clinical symptoms, the latter being supported by a handful of human intervention trials. Additionally, a substantial amount of preclinical trials highlight the potential of diet, fecal microbiota transplantations, as well as pre- and probiotics in modulating the brain's serotonergic neurotransmitter system, starting from the gut. Whether such interventions could truly prevent, reverse or slow down AD progression likewise, should be initially tested in preclinical studies with AD mouse models, including sufficient analytical measurements both in gut and brain. Thereafter, its potential therapeutic effect could be confirmed in rigorously randomized controlled trials in humans, preferentially across the Alzheimer's continuum, but especially from the prodromal up to the mild stages, where both high adherence to such therapies, as well as sufficient room for noticeable enhancement are feasible still. In the end, such studies might aid in the development of a comprehensive approach to tackle this complex multifactorial disease, since serotonin and its derivatives across the microbiota-gut-brain axis might serve as possible biomarkers of disease progression, next to forming a valuable target in AD drug development. In this narrative review, the available evidence concerning the orchestrating role of serotonin within the microbiota-gut-brain axis in the development of AD is summarized and discussed, and general considerations for future studies are highlighted.}, }
@article {pmid34989986, year = {2022}, author = {Philips, CA and Augustine, P and Ganesan, K and Ranade, S and Chopra, V and Patil, K and Shende, S and Ahamed, R and Kumbar, S and Rajesh, S and George, T and Mohanan, M and Mohan, N and Phadke, N and Rani, M and Narayanan, A and Jagan, SM}, title = {The role of gut microbiota in clinical complications, disease severity, and treatment response in severe alcoholic hepatitis.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {41}, number = {1}, pages = {37-51}, pmid = {34989986}, issn = {0975-0711}, mesh = {*Acute Kidney Injury ; *End Stage Liver Disease ; *Gastrointestinal Microbiome ; Granulocyte Colony-Stimulating Factor/therapeutic use ; *Hepatitis, Alcoholic/microbiology ; Humans ; Male ; Severity of Illness Index ; }, abstract = {BACKGROUND: Dysbiotic gut bacteria engage in the development and progression of severe alcoholic hepatitis (SAH). We aimed to characterize bacterial communities associated with clinical events (CE), identify significant bacteria linked to CE, and define bacterial relationships associated with specific CE and outcomes at baseline and after treatment in SAH.<br><br>METHODS: We performed 16-s rRNA sequencing on stool samples (n=38) collected at admission and the last follow-up within 90 days in SAH patients (n=26; 12 corticosteroids; 14 granulocyte colony-stimulating factor, [G-CSF]). Validated pipelines were used to plot bacterial communities, profile functional metabolism, and identify significant taxa and functional metabolites. Conet/NetworkX&#xae; was utilized to identify significant non-random patterns of bacterial co-presence and mutual exclusion for clinical events.<br><br>RESULTS: All the patients were males with median discriminant function (DF) 64, Child-Turcotte-Pugh (CTP) 12, and model for end-stage liver disease (MELD) score 25.5. At admission, 27%, 42%, and 58% had acute kidney injury (AKI), hepatic encephalopathy (HE), and infections respectively; 38.5% died at end of follow-up. Specific bacterial families were associated with HE, sepsis, disease severity, and death. Lachnobacterium and Catenibacterium were associated with HE, and Pediococcus with death after steroid treatment. Change from Enterococcus (promotes AH) to Barnesiella (inhibits E. faecium) was significant after G-CSF. Phenylpropanoid-biosynthesis (innate-immunity) and glycerophospholipid-metabolism (cellular-integrity) pathways in those without infections and the death, respectively, were upregulated. Mutual interactions between Enterococcus cecorum, Acinetobacter schindleri, and Mitsuokella correlated with admission AKI.<br><br>CONCLUSIONS: Specific gut microbiota, their interactions, and metabolites are associated with complications of SAH and treatment outcomes. Microbiota-based precision medicine as adjuvant treatment may be a new therapeutic area.}, }
@article {pmid34987741, year = {2021}, author = {Spindelboeck, W and Halwachs, B and Bayer, N and Huber-Krassnitzer, B and Schulz, E and Uhl, B and Gaksch, L and Hatzl, S and Bachmayr, V and Kleissl, L and Kump, P and Deutsch, A and Stary, G and Greinix, H and Gorkiewicz, G and Högenauer, C and Neumeister, P}, title = {Antibiotic use and ileocolonic immune cells in patients receiving fecal microbiota transplantation for refractory intestinal GvHD: a prospective cohort study.}, journal = {Therapeutic advances in hematology}, volume = {12}, number = {}, pages = {20406207211058333}, pmid = {34987741}, issn = {2040-6207}, abstract = {INTRODUCTION: Treatment-refractory, acute graft-versus-host disease (GvHD) of the lower gastrointestinal tract (GI) after allogeneic hematopoietic stem cell transplantation is life threatening and lacks effective treatment options. While fecal microbiota transplantation (FMT) was shown to ameliorate GI-GvHD, its mechanisms of action and the factors influencing the treatment response in humans remain unclear.The objective of this study is to assess response to FMT treatment, factors influencing response, and to study the mucosal immune cell composition in treatment-refractory GI-GvHD.<br><br>METHODS: Consecutive patients with treatment-refractory GI-GvHD were treated with up to six endoscopically applied FMTs.<br><br>RESULTS: We observed the response to FMT in four out of nine patients with severe, treatment refractory GI-GvHD, associated with a significant survival benefit (p&#x2009;=&#x2009;0.017). The concomitant use of broad-spectrum antibiotics was the main factor associated with FMT failure (p&#x2009;=&#x2009;0.048). In addition, antibiotic administration hindered the establishment of donor microbiota after FMT. Unlike in non-responders, the microbiota characteristics (e.g. &#x3b1;- and &#x3b2;-diversity, abundance of anaerobe butyrate-producers) in responders were more significantly similar to those of FMT donors. During active refractory GI-GvHD, an increased infiltrate of T cells, mainly Th17 and CD8[+] T cells, was observed in the ileocolonic mucosa of patients, while the number of immunomodulatory cells such as regulatory T-cells and type 3 innate lymphoid cells decreased. After FMT, a change in immune cell patterns was induced, depending on the clinical response.<br><br>CONCLUSION: This study increases the knowledge about the crucial effects of antibiotics in patients given FMT for treatment refractory GI-GvHD and defines the characteristic alterations of ileocolonic mucosal immune cells in this setting.}, }
@article {pmid34986765, year = {2022}, author = {D'Amico, F and Barone, M and Tavella, T and Rampelli, S and Brigidi, P and Turroni, S}, title = {Host Microbiomes in Tumor Precision Medicine: How far are we?.}, journal = {Current medicinal chemistry}, volume = {29}, number = {18}, pages = {3202-3230}, doi = {10.2174/0929867329666220105121754}, pmid = {34986765}, issn = {1875-533X}, mesh = {Fecal Microbiota Transplantation ; Humans ; *Microbiota ; *Neoplasms/therapy ; Prebiotics ; Precision Medicine ; *Probiotics/therapeutic use ; }, abstract = {The human gut microbiome has received a crescendo of attention in recent years due to the countless influences on human pathophysiology, including cancer. Research on cancer and anticancer therapy is constantly looking for new hints to improve the response to therapy while reducing the risk of relapse. In this scenario, the gut microbiome and the plethora of microbial-derived metabolites are considered a new opening in the development of innovative anticancer treatments for a better prognosis. This narrative review summarizes the current knowledge on the role of the gut microbiome in the onset and progression of cancer, as well as in response to chemo-immunotherapy. Recent findings regarding the tumor microbiome and its implications for clinical practice are also commented on. Current microbiome-based intervention strategies (i.e., prebiotics, probiotics, live biotherapeutics and fecal microbiota transplantation) are then discussed, along with key shortcomings, including a lack of long-term safety information in patients who are already severely compromised by standard treatments. The implementation of bioinformatic tools applied to microbiomics and other omics data, such as machine learning, has an enormous potential to push research in the field, enabling the prediction of health risk and therapeutic outcomes, for a truly personalized precision medicine.}, }
@article {pmid34985651, year = {2022}, author = {Szychowiak, P and Villageois-Tran, K and Patrier, J and Timsit, JF and Ruppé, &#xc9;}, title = {The role of the microbiota in the management of intensive care patients.}, journal = {Annals of intensive care}, volume = {12}, number = {1}, pages = {3}, pmid = {34985651}, issn = {2110-5820}, abstract = {The composition of the gut microbiota is highly dynamic and changes according to various conditions. The gut microbiota mainly includes difficult-to-cultivate anaerobic bacteria, hence knowledge about its composition has significantly arisen from culture-independent methods based on next-generation sequencing (NGS) such as 16S profiling and shotgun metagenomics. The gut microbiota of patients hospitalized in intensive care units (ICU) undergoes many alterations because of critical illness, antibiotics, and other ICU-specific medications. It is then characterized by lower richness and diversity, and dominated by opportunistic pathogens such as Clostridioides difficile and multidrug-resistant bacteria. These alterations are associated with an increased risk of infectious complications or death. Specifically, at the time of writing, it appears possible to identify distinct microbiota patterns associated with severity or infectivity in COVID-19 patients, paving the way for the potential use of dysbiosis markers to predict patient outcomes. Correcting the microbiota disturbances to avoid their consequences is now possible. Fecal microbiota transplantation is recommended in recurrent C. difficile infections and microbiota-protecting treatments such as antibiotic inactivators are currently being developed. The growing interest in the microbiota and microbiota-associated therapies suggests that the control of the dysbiosis could be a key factor in the management of critically ill patients. The present narrative review aims to provide a synthetic overview of microbiota, from healthy individuals to critically ill patients. After an introduction to the different techniques used for studying the microbiota, we review the determinants involved in the alteration of the microbiota in ICU patients and the latter's consequences. Last, we assess the means to prevent or correct microbiota alteration.}, }
@article {pmid34985325, year = {2022}, author = {Sorboni, SG and Moghaddam, HS and Jafarzadeh-Esfehani, R and Soleimanpour, S}, title = {A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders.}, journal = {Clinical microbiology reviews}, volume = {35}, number = {1}, pages = {e0033820}, pmid = {34985325}, issn = {1098-6618}, mesh = {Dysbiosis/metabolism/therapy ; *Gastrointestinal Microbiome/physiology ; Humans ; *Nervous System Diseases/therapy ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {The human body is full of an extensive number of commensal microbes, consisting of bacteria, viruses, and fungi, collectively termed the human microbiome. The initial acquisition of microbiota occurs from both the external and maternal environments, and the vast majority of them colonize the gastrointestinal tract (GIT). These microbial communities play a central role in the maturation and development of the immune system, the central nervous system, and the GIT system and are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental factors, lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect the composition of the gut microbiota. Recent publications have highlighted that an imbalance in the gut microflora, known as dysbiosis, is associated with the onset and progression of neurological disorders. Moreover, characterization of the microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical and clinical research on interventions related to the gut microbiome for treating neurological conditions, including autism spectrum disorders, Parkinson's disease, schizophrenia, multiple sclerosis, Alzheimer's disease, epilepsy, and stroke, hold significant promise. This review aims to present a comprehensive overview of the potential involvement of the human gut microbiome in the pathogenesis of neurological disorders, with a particular emphasis on the potential of microbe-based therapies and/or diagnostic microbial biomarkers. This review also discusses the potential health benefits of the administration of probiotics, prebiotics, postbiotics, and synbiotics and fecal microbiota transplantation in neurological disorders.}, }
@article {pmid34982410, year = {2022}, author = {Picciariello, A and Rinaldi, M and Dibra, R and Trigiante, G and Tomasicchio, G and Lantone, G and De Fazio, M}, title = {Ageing with sacral nerve modulation for fecal incontinence: how many patients get benefit after more than 10 years?.}, journal = {Updates in surgery}, volume = {74}, number = {1}, pages = {185-191}, pmid = {34982410}, issn = {2038-3312}, mesh = {Aging ; *Electric Stimulation Therapy ; Electrodes, Implanted ; *Fecal Incontinence/therapy ; Humans ; Quality of Life ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Sacral nerve modulation (SNM) has represented a major advancement in the minimally invasive management of patients with fecal incontinence (FI). Although the success rate in the short-medium term has widely been demonstrated, the very long-term outcomes are poorly investigated. This study aims to assess the effectiveness of SNM in a cohort of patients with a follow-up longer than 10 years. Clinical records of patients submitted to SNM for FI in our tertiary referral colorectal Unit between 1998 and 2010 were retrospectively reviewed looking for status of the implantable pulse generator (IPG), follow-up duration, severity of FI by the St Marks' score and quality of life. 58 patients fulfilled the entry criteria and 36 (58%, median follow-up, 12 years) accepted to take part to the telephone interview, while 22 (38%) were lost to the follow-up. Nineteen patients had their IPG removed (Group A) while 17 (27%) had the SNM still active after a median follow-up of 13 years (Group B). In the group A, the median baseline St Marks' score was 13 and did not change after the IPG removal. In group B, the median baseline St Marks' score was 14, at last IPG substitution, it was of 7 and at the last follow-up dropped to 4. In the group A, the median SF-12 physical and mental scores did not change significantly while they improved significantly in group B. A progressive deterioration of the success rate of SNM with the time has been documented after a very long-term follow-up.}, }
@article {pmid34980687, year = {2022}, author = {Gweon, TG and Lee, YJ and Kim, KO and Yim, SK and Soh, JS and Kim, SY and Park, JJ and Shin, SY and Lee, TH and Choi, CH and Cho, YS and Yong, D and Chung, JW and Lee, KJ and Lee, OY and Choi, MG and Choi, M and , }, title = {Clinical Practice Guidelines for Fecal Microbiota Transplantation in Korea.}, journal = {Journal of neurogastroenterology and motility}, volume = {28}, number = {1}, pages = {28-42}, pmid = {34980687}, issn = {2093-0879}, abstract = {Fecal microbiota transplantation (FMT) is a highly efficacious and safe modality for the treatment of recurrent or refractory Clostridioides difficile infection (CDI), with overall success rates of 90%. Thus, FMT has been widely used for 10 years. The incidence and clinical characteristics of CDI, the main indication for FMT, differ between countries. To date, several guidelines have been published. However, most of them were published in Western countries and therefore cannot represent the Korean national healthcare systems. One of the barriers to performing FMT is a lack of national guidelines. Accordingly, multidisciplinary experts in this field have developed practical guidelines for FMT. The purpose of these guidelines is to aid physicians performing FMT, which can be adapted to treat CDI and other conditions.}, }
@article {pmid34980222, year = {2022}, author = {Chen, Y and Liu, Y and Wang, Y and Chen, X and Wang, C and Chen, X and Yuan, X and Liu, L and Yang, J and Zhou, X}, title = {Prevotellaceae produces butyrate to alleviate PD-1/PD-L1 inhibitor-related cardiotoxicity via PPARα-CYP4X1 axis in colonic macrophages.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {41}, number = {1}, pages = {1}, pmid = {34980222}, issn = {1756-9966}, mesh = {Animals ; Butyrates/pharmacology/*therapeutic use ; Cardiotoxicity/*drug therapy ; Colon/*pathology ; Cytochrome P-450 Enzyme System/*metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Humans ; Immune Checkpoint Inhibitors/*adverse effects ; Macrophages/*metabolism ; Male ; Mice ; Transfection ; }, abstract = {BACKGROUND: Immune checkpoint inhibitor-related cardiotoxicity is one of the most lethal adverse effects, and thus, the identification of underlying mechanisms for developing strategies to overcome it has clinical importance. This study aimed to investigate whether microbiota-host interactions contribute to PD-1/PD-L1 inhibitor-related cardiotoxicity.<br><br>METHODS: A mouse model of immune checkpoint inhibitor-related cardiotoxicity was constructed by PD-1/PD-L1 inhibitor BMS-1 (5 and 10&#x2009;mg/kg), and cardiomyocyte apoptosis and cardiotoxicity were determined by hematoxylin and eosin, Masson's trichome and TUNEL assays. 16S rRNA sequencing was used to define the gut microbiota composition. Gut microbiota metabolites short-chain fatty acids (SCFAs) were determined by HPLC. The serum levels of myocardial enzymes (creatine kinase, aspartate transaminase, creatine kinase-MB and lactate dehydrogenase) and the production of M1 factors (TNF-&#x3b1; and IL-1&#x3b2;) were measured by ELISA. The colonic macrophage phenotype was measured by mmunofluorescence and qPCR. The expression of Claudin-1, Occludin, ZO-1 and p-p65 was measured by western blot. The gene expression of peroxisome proliferator-activated receptor &#x3b1; (PPAR&#x3b1;) and cytochrome P450 (CYP) 4X1 was determined using qPCR. Statistical analyses were performed using Student's t-test for two-group comparisons, and one-way ANOVA followed by Student-Newman-Keul test for multiple-group comparisons.<br><br>RESULTS: We observed intestinal barrier injury and gut microbiota dysbiosis characterized by Prevotellaceae and Rikenellaceae genus depletion and Escherichia-Shigella and Ruminococcaceae genus enrichment, accompanied by low butyrate production and M1-like polarization of colonic macrophages in BMS-1 (5 and 10&#x2009;mg/kg)-induced cardiotoxicity. Fecal microbiota transplantation mirrored the effect of BMS-1 on cardiomyocyte apoptosis and cardiotoxicity, while macrophage depletion and neutralization of TNF-&#x3b1; and IL-1&#x3b2; greatly attenuated BMS-1-induced cardiotoxicity. Importantly, Prevotella loescheii recolonization and butyrate supplementation alleviated PD-1/PD-L1 inhibitor-related cardiotoxicity. Mechanistically, gut microbiota dysbiosis promoted M1-like polarization of colonic macrophages and the production of proinflammatory factors TNF-&#x3b1; and IL-1&#x3b2; through downregulation of PPAR&#x3b1;-CYP4X1 axis.<br><br>CONCLUSIONS: Intestinal barrier dysfunction amplifies PD-1/PD-L1 inhibitor-related cardiotoxicity by upregulating proinflammatory factors TNF-&#x3b1; and IL-1&#x3b2; in colonic macrophages via downregulation of butyrate-PPAR&#x3b1;-CYP4X1 axis. Thus, targeting gut microbiota to polarize colonic macrophages away from the M1-like phenotype could provide a potential therapeutic strategy for PD-1/PD-L1 inhibitor-related cardiotoxicity.}, }
@article {pmid34978141, year = {2022}, author = {Michels, N and Zouiouich, S and Vanderbauwhede, B and Vanacker, J and Indave Ruiz, BI and Huybrechts, I}, title = {Human microbiome and metabolic health: An overview of systematic reviews.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {23}, number = {4}, pages = {e13409}, doi = {10.1111/obr.13409}, pmid = {34978141}, issn = {1467-789X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*Diabetes Mellitus, Type 2 ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Non-alcoholic Fatty Liver Disease ; Obesity ; *Probiotics ; Systematic Reviews as Topic ; }, abstract = {To summarize the microbiome's role in metabolic disorders (insulin resistance, hyperglycemia, type 2 diabetes, obesity, hyperlipidemia, hypertension, nonalcoholic fatty liver disease [NAFLD], and metabolic syndrome), systematic reviews on observational or interventional studies (prebiotics/probiotics/synbiotics/transplant) were searched in MEDLINE and Embase until September 2020. The 87 selected systematic reviews included 57 meta-analyses. Methodological quality (AMSTAR2) was moderate in 62%, 12% low, and 26% critically low. Observational studies on obesity (10 reviews) reported less gut bacterial diversity with higher Fusobacterium, Lactobacillus reuteri, Bacteroides fragilis, and Staphylococcus aureus, whereas lower Methanobrevibacter, Lactobacillus plantarum, Akkermansia muciniphila, and Bifidobacterium animalis compared with nonobese. For diabetes (n = 1), the same was found for Fusobacterium and A. muciniphila, whereas higher Ruminococcus and lower Faecalibacterium, Roseburia, Bacteroides vulgatus, and several Bifidobacterium spp. For NAFLD (n = 2), lower Firmicutes, Rikenellaceae, Ruminococcaceae, whereas higher Escherichia and Lactobacillus were detected. Discriminating bacteria overlapped between metabolic disorders, those with high abundance being often involved in inflammation, whereas those with low abundance being used as probiotics. Meta-analyses (n = 54) on interventional studies reported 522 associations: 54% was statistically significant with intermediate effect size and moderate between-study heterogeneity. Meta-evidence was highest for probiotics and lowest for fecal transplant. Future avenues include better methodological quality/comparability, testing functional differences, new intervention strategies, and considerating other body habitats and kingdoms.}, }
@article {pmid34977119, year = {2021}, author = {Pan, B and Liu, X and Shi, J and Chen, Y and Xu, Z and Shi, D and Ruan, G and Wang, F and Huang, Y and Xu, C}, title = {A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {775216}, pmid = {34977119}, issn = {2296-861X}, abstract = {Background and aims: Metabolic syndrome (MetS), accompanied with significant intestinal dysbiosis, causes a great public health burden to human society. Here, we carried out a meta-analysis to qualify randomized controlled trials (RCTs) and to systematically evaluate the effect of microbial therapy on MetS. Methods and results: Forty-two RCTs were eligible for this meta-analysis after searching the PubMed, Cochrane, and Embase databases. Pooled estimates demonstrated that treatment with microbial therapy significantly reduced the waist circumference (WC) (SMD = -0.26, 95% CI -0.49, -0.03), fasting blood glucose (FBG) (SMD = -0.35, 95% CI -0.52, -0.18), total cholesterol (TC) (SMD = -0.36, 95% CI -0.55, -0.17), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.42, 95% CI -0.61, -0.22), and triacylglycerol (TG)(SMD = -0.38, 95% CI -0.55, -0.20), but increased the high-density lipoprotein cholesterol (HDL-C) (SMD = 0.28, 95% CI.03, 0.52). Sensitivity analysis indicated that after eliminating one study utilizing Bifidobacteriumlactis, results became statistically significant in diastolic blood pressure (DBP) (SMD = -0.24, 95% CI -0.41, -0.07) and in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (SMD = -0.28, 95% CI -0.54, -0.03), while the body mass index (BMI) showed significant difference after eliminating one study utilizing oat bran (SMD = -0.16, 95% CI -0.31, -0.01). There was still no significant effect in systolic blood pressure (SBP) and in hemoglobin A1c (HbA1c%). Conclusion: In patients with MetS, the conditioning with microbial therapy notably improves FBG, TC, TG, HDL-C, LDL-C, WC, BMI (except for the study using oat bran), HOMA-IR, and DBP (except for the Study using Bifidobacteriumlactis), however, with no effect in SBP and in HbA1c%.}, }
@article {pmid34976874, year = {2021}, author = {Li, S and Wei, J and Chen, T}, title = {Editorial: Gut Microbiota in the Occurrence, Development and Treatment of Gut-Brain Disorders.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {808454}, pmid = {34976874}, issn = {2235-2988}, }
@article {pmid34976247, year = {2021}, author = {Marlicz, W and Skonieczna-Żydecka, K and Krynicka, P and Łoniewski, I and Rydzewska, G}, title = {Probiotics in irritable bowel syndrome - is the quest for the right strain over? Rapid review of existing guidelines and recommendations.}, journal = {Przeglad gastroenterologiczny}, volume = {16}, number = {4}, pages = {369-382}, pmid = {34976247}, issn = {1895-5770}, abstract = {Irritable bowel syndrome (IBS) - functional gastrointestinal disorder (FGIDs) and disorder of gut-brain interaction (DGBIs) - has emerged as an important medical problem with an impact on health care systems, affecting patients' quality of life. The management of IBS consists of pharmacological and non-pharmacological treatments; however, the data of their long-term efficacy are scarce. Modulation of gastrointestinal microbiota, by means of probiotics and prebiotics, is often sought and advertised as a popular treatment modality in IBS. Faecal microbiota transplantation (FMT) awaits recommendations for IBS treatment and requires more methodological assessments. To date, numerous guidelines and recommendations have been published on the role of probiotics in IBS. Because no probiotic claim for probiotics in foods has yet been granted by the European Food and Safety Authority (EFSA), medical practitioners still recommend probiotics on the basis of available literature and recommendations released by independent health authorities. We aimed to summarize published formal recommendations and guidelines regarding the clinical effectiveness of available probiotic strains and conduct a random-effects meta-analysis of outcomes for which ≥ 2 studies contributed data on the same probiotic strain recommended to adults with IBS. Based on available and most recent guidelines, we report that probiotics, as a group, may be an effective treatment for global symptoms and abdominal pain in IBS, with the strongest effect for genus Lactobacillus. Our current and updated meta-analysis is in line with several reports documenting significant effects of Lactobacillus plantarum (Lp299v) in reducing the risk of global symptoms and their persistence, which could assist clinicians in making the choice for the right probiotic strain in IBS patients.}, }
@article {pmid34975748, year = {2021}, author = {Ye, X and Liu, Y and Hu, J and Gao, Y and Ma, Y and Wen, D}, title = {Chlorogenic Acid-Induced Gut Microbiota Improves Metabolic Endotoxemia.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {762691}, pmid = {34975748}, issn = {1664-2392}, mesh = {Animals ; Chlorogenic Acid/pharmacology/*therapeutic use ; Diet, High-Fat/adverse effects ; Endotoxemia/*drug therapy/metabolism ; Gastrointestinal Microbiome/*drug effects/physiology ; Male ; Metabolic Syndrome/*drug therapy/metabolism ; Mice ; Mice, Inbred C57BL ; Weight Gain/*drug effects/physiology ; }, abstract = {BACKGROUND: Coffee can regulate glucose homeostasis but the underlying mechanism is unclear. This study investigated the preventive and therapeutic effects of chlorogenic acid (CGA), a polyphenol that is found in coffee, on obesity and obesity-related metabolic endotoxemia.<br><br>METHOD: Male 4-week-old C57BL/6 mice were fed either normal chow or a high-fat diet or 20 weeks and half the mice in each group were gavaged with CGA. Oral glucose tolerance tests (OGTTs) and insulin tolerance tests (ITTs) were performed. Markers of inflammation and intestinal barrier function were assayed. The composition of the gut microbiota was analyzed by 16S rRNA high-throughput pyrosequencing. The role of CGA-altered microbiota in metabolic endotoxemia was verified by fecal microbiota transplantation.<br><br>RESULTS: CGA protected against HFD-induced weight gain, decreased the relative weight of subcutaneous and visceral adipose, improved intestinal barrier integrity, and prevented glucose metabolic disorders and endotoxemia (P <0.05). CGA significantly changed the composition of the gut microbiota and increased the abundance of short chain fatty acid (SCFA)-producers (e.g., Dubosiella, Romboutsia, Mucispirillum, and Faecalibaculum) and Akkermansia, which can protect the intestinal barrier. In addition, mice with the CGA-altered microbiota had decreased body weight and fat content and inhibited metabolic endotoxemia.<br><br>CONCLUSION: CGA-induced changes in the gut microbiota played an important role in the inhibition of metabolic endotoxemia in HFD-fed mice.}, }
@article {pmid34970503, year = {2021}, author = {Cardile, S and Del Chierico, F and Candusso, M and Reddel, S and Bernaschi, P and Pietrobattista, A and Spada, M and Torre, G and Putignani, L}, title = {Impact of Two Antibiotic Therapies on Clinical Outcome and Gut Microbiota Profile in Liver Transplant Paediatric Candidates Colonized by Carbapenem-Resistant Klebsiella pneumoniae CR-KP.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {730904}, pmid = {34970503}, issn = {2235-2988}, mesh = {Anti-Bacterial Agents/therapeutic use ; Carbapenems/pharmacology ; Child ; *Gastrointestinal Microbiome ; Humans ; Klebsiella ; *Klebsiella Infections/drug therapy/prevention &amp; control ; Klebsiella pneumoniae/genetics ; *Liver Transplantation ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Colonization by multidrug-resistant (MDR) organisms in liver transplant (LT) candidates significantly affects the LT outcome. To date, consensus about patient management is lacking, including microbiological screening indications. This pilot study aimed to evaluate the impact of carbapenem-resistant Klebsiella pneumoniae (CR-KP) colonization in LT paediatric candidates to enable optimal prevention and therapeutic strategies that exploit both clinical and microbiological approaches. Seven paediatric patients colonized by CR-KP were evaluated before and until one-year post LT. At the time of the transplant, patients were stratified based on antibiotic (ATB) prophylaxis into two groups: 'standard ATB' (standard ATB prophylaxis), and 'targeted ATB' (MDR antibiogram-based ATB prophylaxis). Twenty-eight faecal samples were collected during follow-up and used for MDR screening and gut microbiota 16S rRNA-based profiling. Post-transplant hospitalization duration was comparable for both groups. With the exception of one patient, no serious infections and/or complications, nor deaths were recorded. A progressive MDR decontamination was registered. In the 'standard ATB' group, overall bacterial richness increased. Moreover, 6 months after LT, Lactobacillus and Bulleidia were increased and Enterobacteriaceae and Klebsiella spp. were reduced. In the 'targeted ATB' group Klebsiella spp., Ruminococcus gnavus, Erysipelotrichaceae, and Bifidobacterium spp. were increased 12 months after LT. In conclusion, both antibiotics prophylaxis do not affect nor LT outcomes or the risk of intestinal bacterial translocation. However, in the 'standard ATB' group, gut microbiota richness after LT was increased, with an increase of beneficial lactic acid- and short-chain fatty acids (SCFA)-producing bacteria and the reduction of harmful Enterobacteriaceae and Klebsiella spp. It could therefore be appropriate to administer standard prophylaxis, reserving the use of ATB-based molecules only in case of complications.}, }
@article {pmid34970262, year = {2021}, author = {Gao, G and Ma, T and Zhang, T and Jin, H and Li, Y and Kwok, LY and Zhang, H and Sun, Z}, title = {Adjunctive Probiotic Lactobacillus rhamnosus Probio-M9 Administration Enhances the Effect of Anti-PD-1 Antitumor Therapy via Restoring Antibiotic-Disrupted Gut Microbiota.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {772532}, pmid = {34970262}, issn = {1664-3224}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Bacteroides/drug effects/growth &amp; development ; Bifidobacterium/drug effects/growth &amp; development ; Cell Line, Tumor ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Immune Checkpoint Inhibitors/*administration &amp; dosage ; *Lacticaseibacillus rhamnosus ; Mice, Inbred BALB C ; Neoplasms/microbiology/*therapy ; Probiotics/*therapeutic use ; Programmed Cell Death 1 Receptor/*antagonists &amp; inhibitors ; Mice ; }, abstract = {Emerging evidence supports that the efficacy of immune checkpoint blockade (ICB) therapy is associated with the host's gut microbiota, as prior antibiotic intake often leads to poor outcome and low responsiveness toward ICB treatment. Therefore, we hypothesized that the efficacy of ICB therapy like anti-programmed cell death protein-1 (PD-1) treatment required an intact host gut microbiota, and it was established that probiotics could enhance the recovery of gut microbiota disruption by external stimuli. Thus, the present study aimed to evaluate the effect of the probiotics, Lactobacillus rhamnosus Probio-M9, on recovering antibiotic-disrupted gut microbiota and its impact on the outcome of ICB therapy in tumor-bearing mice. We first disrupted the mouse microbiota by antibiotics and then remediated the gut microbiota by probiotics or naturally. Tumor transplantation was then performed, followed by anti-PD-1-based antitumor therapy. Changes in the fecal metagenomes and the tumor suppression effect were monitored during different stages of the experiment. Our results showed that Probio-M9 synergized with ICB therapy, significantly improving tumor inhibition compared with groups not receiving the probiotic treatment (P < 0.05 at most time points). The synergistic effect was accompanied by effective restoration of antibiotic-disrupted fecal microbiome that was characterized by a drastically reduced Shannon diversity value and shifted composition of dominating taxa. Moreover, probiotic administration significantly increased the relative abundance of beneficial bacteria (e.g., Bifidobacterium pseudolongum, Parabacteroides distasonis, and some Bacteroides species; 0.0001 < P < 0.05). The gut microbiome changes were accompanied by mild reshaping of the functional metagenomes characterized by enrichment in sugar degradation and vitamin and amino acid synthesis pathways. Collectively, this study supported that probiotic administration could enhance the efficacy and responsiveness of anti-PD-1-based immunotherapy, and Probio-M9 could be a potential candidate of microbe-based synergistic tumor therapeutics. The preclinical data obtained here would support the design of future human clinical trials for further consolidating the current findings and for safety assessment of probiotic adjunctive treatment in ICB therapy.}, }
@article {pmid34966755, year = {2021}, author = {Hu, Y and Ye, Z and Wu, M and She, Y and Li, L and Xu, Y and Qin, K and Hu, Z and Yang, M and Lu, F and Ye, Q}, title = {The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {766126}, pmid = {34966755}, issn = {2296-858X}, abstract = {Ulcerative Colitis (UC) is a chronic inflammatory bowel disease. The prolonged course of UC and the lack of effective treatment management make it difficult to cure, affecting the health and life safety of patients. Although UC has received more attention, the etiology and pathogenesis of UC are still unclear. Therefore, it is urgent to establish an updated and comprehensive understanding of UC and explore effective treatment strategies. Notably, sufficient evidence shows that the intestinal microbiota plays an important role in the pathogenesis of UC, and the treating method aimed at improving the balance of the intestinal microbiota exhibits a therapeutic potential for UC. This article reviews the relationship between the genetic, immunological and microbial risk factors with UC. At the same time, the UC animal models related to intestinal microbiota dysbiosis induced by chemical drugs were evaluated. Finally, the potential value of the therapeutic strategies for restoring intestinal microbial homeostasis and treating UC were also investigated. Comprehensively, this study may help to carry out preclinical research, treatment theory and methods, and health management strategy of UC, and provide some theoretical basis for TCM in the treatment of UC.}, }
@article {pmid34965174, year = {2022}, author = {Hiippala, K and Khan, I and Ronkainen, A and Boulund, F and Vähä-Mäkilä, H and Suutarinen, M and Seifert, M and Engstrand, L and Satokari, R}, title = {Novel strain of Pseudoruminococcus massiliensis possesses traits important in gut adaptation and host-microbe interactions.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2013761}, pmid = {34965174}, issn = {1949-0984}, mesh = {Adaptation, Physiological ; Bacterial Proteins/genetics/metabolism ; Butyrates/metabolism ; Firmicutes/classification/genetics/*isolation &amp; purification/*physiology ; Gastrointestinal Microbiome ; Genome, Bacterial ; Glycoside Hydrolases/genetics/metabolism ; Host Microbial Interactions ; Humans ; Intestines/*microbiology ; }, abstract = {Fecal microbiota transplantation (FMT) is an efficient treatment for recurrent Clostridioides difficile infection and currently investigated as a treatment for other intestinal and systemic diseases. Better understanding of the species potentially transferred in FMT is needed. We isolated from a healthy fecal donor a novel strain E10-96H of Pseudoruminococcus massiliensis, a recently described strictly anaerobic species currently represented only by the type strain. The whole genome sequence of E10-96H had over 98% similarity with the type strain. E10-96H carries 20 glycoside hydrolase encoding genes, degrades starch in vitro and thus may contribute to fiber degradation, cross-feeding of other species and butyrate production in the intestinal ecosystem. The strain carries pilus-like structures, harbors pilin genes in its genome and adheres to enterocytes in vitro but does not provoke a proinflammatory response. P. massiliensis seems to have commensal behavior with the host epithelium, and its role in intestinal ecology should be studied further.}, }
@article {pmid34963452, year = {2021}, author = {Lin, H and Guo, Q and Wen, Z and Tan, S and Chen, J and Lin, L and Chen, P and He, J and Wen, J and Chen, Y}, title = {The multiple effects of fecal microbiota transplantation on diarrhea-predominant irritable bowel syndrome (IBS-D) patients with anxiety and depression behaviors.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {233}, pmid = {34963452}, issn = {1475-2859}, support = {No. 81770529//National Natural Science Foundation of China/ ; No. 82070543//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Aged ; Anxiety/*microbiology/*therapy ; Depression/*microbiology/*therapy ; Diarrhea/microbiology/therapy ; Escherichia/classification ; Eubacterium/classification ; Faecalibacterium/classification ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Hemiterpenes/metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Irritable Bowel Syndrome/complications/*microbiology/therapy ; Male ; *Metagenome ; Middle Aged ; Pentanoic Acids/metabolism ; Quality of Life ; }, abstract = {BACKGROUND: Anxiety and depression are complications in Irritable bowel syndrome (IBS) patients. In this study, we recruited 18 IBS patients with mild-modest anxiety and depression behaviors, and after the screening, we defined the FMT treatment group (n = 9) and the control group (n = 9). The IBS symptom severity scale (IBS-SSS), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), Irritable Bowel Syndrome Quality of Life (IBS-QOL) and Bristol stool scale (BSS) were evaluated one week before FMT (baseline), one-week-, one-month-, two-month-, and three-month-following FMT. Meanwhile, we determined the SCFAs in the patient's feces and serum and continued the metagenomic analysis of the microorganisms in the patient's feces.<br><br>RESULTS: The results showed that the patient's anxiety and depression behavior gradually improved with FMT treatment. Moreover, the illness and quality of life had also been relieved significantly. The content of isovaleric acid and valeric acid was significantly reduced in the FMT group compared to the Col group. Metagenomic analysis showed that FMT treatment decreased the abundance of Faecalibacterium, Eubacterium and Escherichia. From KEGG functional analysis, we confirmed that the top five abundant pathways were "bacterial chemotaxis, "flagellar assembly", "glycine, serine and threonine metabolism", "apoptosis", and "bacterial invasion of epithelial cells".<br><br>CONCLUSIONS: FMT treatment can effectively alleviate the anxiety and depression behaviors of IBS-D patients and reduce the IBS-SSS score, indicating that FMT can improve patients' symptoms. The high throughput sequencing results show that Bifidobacterium and Escherichia play the most critical role in the formation and recovery of IBS-D patients. The GC/MS data indicated that faeces isovaleric acid and valeric acid might be more suitable as a metabolic indicator of IBS-D remission. Trial registration&#xa0;ChiCTR, ChiCTR1900024924, Registered 3 August 2019, https://www.chictr.org.cn/showproj.aspx?proj=41676 .}, }
@article {pmid34962114, year = {2021}, author = {Jang, S and Kim, Y and Lee, C and Kwon, B and Noh, J and Jee, JJ and Yoon, SS and Koh, H and Park, S}, title = {The Effect of Formula-based Nutritional Treatment on Colitis in a Murine Model.}, journal = {Journal of Korean medical science}, volume = {36}, number = {50}, pages = {e342}, pmid = {34962114}, issn = {1598-6357}, support = {//Korea Health Industry Development Institute/Korea ; }, mesh = {Animals ; *Colitis/chemically induced/pathology/therapy ; *Crohn Disease ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Humans ; Mice ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Exclusive enteral nutrition (EEN) induces remission in pediatric Crohn's disease (CD). The exact mechanism of EEN therapy in CD is unknown, but alteration of the intestinal microflora after EEN is thought to affect mucosal healing. To determine the link between EEN therapy and therapeutic efficacy in CD, we established a murine model of dextran sulfate sodium (DSS)-induced colitis and applied EEN therapy.<br><br>METHODS: Eight-week-old C57BL/6 mice were administered DSS for 4 days to induce colitis, and either normal chow (NC) or EEN was administered for the following 4 days. The mice were grouped according to the feeding pattern after DSS administration: DSS/NC and DSS/EEN groups. The clinical course was confirmed via daily observation of the weight and stool. Fecal samples were collected and 16sRNA sequencing was used. The mice were sacrificed to confirm colonic histopathology.<br><br>RESULTS: Weight reduction and increase in disease activity were observed as the day progressed for 4 days after DSS administration. There was significant weight recovery and improvement in disease activity in the EEN group compared to that in the NC group. Verrucomicrobia and Proteobacteria abundances tended to increase and Bacteroidetes abundance decreased in the EEN group. In the EEN group, significant changes in the &#x3b2;-diversity of the microbiota were observed. In the analysis of microbiome species, abundances of Akkermansia muciniphila, Clostridium cocleatum, mucin-degrading bacteria, Flintibacter butyricus, and Parabacteroides goldsteinii, which are beneficial microbiota, were significantly increased in the EEN group compared to those in the NC group. More abundant mucins were confirmed in the colonic histopathology of the EEN group. These microbial and histopathological differences suggested that EEN might improve colitis symptoms in a murine colitis model by promoting mucin recycling and subsequently inducing the healing effect of the gut barrier.<br><br>CONCLUSION: EEN showed clinical efficacy in a murine model of colitis. Based on the increase in mucin-degrading bacteria and the pathological increase in mucin production after EEN administration, it can be observed that mucin plays an important role in the therapeutic effect of EEN.}, }
@article {pmid34960067, year = {2021}, author = {Minaya, DM and Weinstein, NL and Czaja, K}, title = {Development of a 3D-Printed High Temperature Resin Cecal Fistula Implant for Long-Term and Minimally Invasive Access to the Gut Microbiome.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, pmid = {34960067}, issn = {2072-6643}, support = {5R01DC013904//National Institute of Health/ ; 2021//UGA Obesity Initiative Grant/ ; }, mesh = {Animals ; Cecum/microbiology/*surgery ; *Gastrointestinal Microbiome ; Male ; Minimally Invasive Surgical Procedures ; Monitoring, Physiologic/*instrumentation ; *Printing, Three-Dimensional ; *Prostheses and Implants ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Microbiota dysbiosis has been associated with chronic diseases ranging from gastrointestinal inflammatory and metabolic conditions to neurological changes affecting the gut-brain neural axis, mental health, and general well-being. However, current animal studies using oral gavage and gnotobiotic animals do not allow for non-invasive long-term access to gut microbiome. The purpose of the present study was to evaluate the feasibility of 3D-printed fistula implants through the body wall and into the cecum of rats to obtain long-term access to gut microbiome. Cecal fistulas were designed and 3D-printed using a high temperature resin (Formlabs; acrylic and methacrylic mixture). Nine male Sprague-Dawley rats underwent the fistula implantation. Food intake, body weight, and body fat were measured to determine the impact of fistula manipulation. Gut microbiome, vagal afferents in the hindbrain, and microglia activation were analyzed to determine if fistula implantation disrupted the gut-brain neural axis. We found that the procedure induced a transient decrease in microbial diversity in the gut that resolved within a few weeks. Fistula implantation had no impact on food intake, body weight, fat mass, or microglia activation. Our study shows that 3D-printed cecal fistula implantation is an effective procedure that allows long-term and minimally invasive access to gut microbiome.}, }
@article {pmid34960049, year = {2021}, author = {Chernikova, MA and Flores, GD and Kilroy, E and Labus, JS and Mayer, EA and Aziz-Zadeh, L}, title = {The Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, pmid = {34960049}, issn = {2072-6643}, support = {AR170062//United States Department of Defense/ ; }, mesh = {Animals ; Autism Spectrum Disorder/*microbiology ; Brain/*microbiology ; Brain-Gut Axis/*physiology ; Gastrointestinal Diseases/microbiology/*psychology ; Gastrointestinal Microbiome/*physiology ; Humans ; }, abstract = {Gastrointestinal dysfunction is one of the most prevalent physiological symptoms of autism spectrum disorder (ASD). A growing body of largely preclinical research suggests that dysbiotic gut microbiota may modulate brain function and social behavior, yet little is known about the mechanisms that underlie these relationships and how they may influence the pathogenesis or severity of ASD. While various genetic and environmental risk factors have been implicated in ASD, this review aims to provide an overview of studies elucidating the mechanisms by which gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development, in at least a subgroup of individuals with gastrointestinal problems. Specifically, we review the brain-gut-microbiome system and discuss findings from current animal and human studies as they relate to social-behavioral and neurological impairments in ASD, microbiota-targeted therapies (i.e., probiotics, fecal microbiota transplantation) in ASD, and how microbiota may influence the brain at molecular, structural, and functional levels, with a particular interest in social and emotion-related brain networks. A deeper understanding of microbiome-brain-behavior interactions has the potential to inform new therapies aimed at modulating this system and alleviating both behavioral and physiological symptomatology in individuals with ASD.}, }
@article {pmid34959977, year = {2021}, author = {Sobocki, BK and Kaźmierczak-Siedlecka, K and Folwarski, M and Hawryłkowicz, V and Makarewicz, W and Stachowska, E}, title = {Pancreatic Cancer and Gut Microbiome-Related Aspects: A Comprehensive Review and Dietary Recommendations.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, pmid = {34959977}, issn = {2072-6643}, mesh = {Dysbiosis/microbiology/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Pancreatic Neoplasms/*microbiology ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; Synbiotics/administration &amp; dosage ; Tumor Microenvironment ; }, abstract = {Gut microbiota plays a significant role in the human body providing many beneficial effects on the host. However, its dysbiotic alterations may affect the tumorigenic pathway and then trigger the development of pancreatic cancer. This dysbiosis can also modulate the aggressiveness of the tumor, influencing the microenvironment. Because pancreatic cancer is still one of the most lethal cancers worldwide with surgery as the only method that influences prognosis and has curative potential, there is a need to search for other strategies which will enhance the efficiency of standard therapy and improve patients' quality of life. The administration of prebiotics, probiotics, next-generation probiotics (Faecalibacterium prausnitzii, Akkermansia muciniphila), synbiotics, postbiotics, and fecal microbiota transplantation through multiple mechanisms affects the composition of the gut microbiota and may restore its balance. Despite limited data, some studies indicate that the aforementioned methods may allow to achieve better effect of pancreatic cancer treatment and improve therapeutic strategies for pancreatic cancer patients.}, }
@article {pmid34959505, year = {2021}, author = {Pane, S and Ristori, MV and Gardini, S and Russo, A and Del Chierico, F and Putignani, L}, title = {Clinical Parasitology and Parasitome Maps as Old and New Tools to Improve Clinical Microbiomics.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, pmid = {34959505}, issn = {2076-0817}, support = {Ricerca Corrente 2020 and 2021//Italian Ministry of Health/ ; }, abstract = {A growing body of evidence shows that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, which reduces host damage. Herein, we discuss how diagnostic parasitology may contribute to designing clinical metagenomic pipelines and FMT programs, especially in pediatric subjects. The consequences of more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.}, }
@article {pmid34957088, year = {2021}, author = {Bi, C and Xiao, G and Liu, C and Yan, J and Chen, J and Si, W and Zhang, J and Liu, Z}, title = {Molecular Immune Mechanism of Intestinal Microbiota and Their Metabolites in the Occurrence and Development of Liver Cancer.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {702414}, pmid = {34957088}, issn = {2296-634X}, abstract = {Intestinal microorganisms are closely associated with immunity, metabolism, and inflammation, and play an important role in health and diseases such as inflammatory bowel disease, diabetes, cardiovascular disease, Parkinson's disease, and cancer. Liver cancer is one of the most fatal cancers in humans. Most of liver cancers are slowly transformed from viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease. However, the relationship between intestinal microbiota and their metabolites, including short-chain fatty acids, bile acids, indoles, and ethanol, and liver cancer remains unclear. Here, we summarize the molecular immune mechanism of intestinal microbiota and their metabolites in the occurrence and development of liver cancer and reveal the important role of the microbiota-gut-liver axis in liver cancer. In addition, we describe how the intestinal flora can be balanced by antibiotics, probiotics, postbiotics, and fecal bacteria transplantation to improve the treatment of liver cancer. This review describes the immunomolecular mechanism of intestinal microbiota and their metabolites in the occurrence and development of hepatic cancer and provides theoretical evidence support for future clinical practice.}, }
@article {pmid34956503, year = {2021}, author = {Zhao, D and Ye, C and Zhang, S and Lv, X and Yang, B}, title = {Analysis of risk factors for early clinical recurrence of inflammatory bowel disease after fecal microbiota transplantation.}, journal = {American journal of translational research}, volume = {13}, number = {11}, pages = {12875-12886}, pmid = {34956503}, issn = {1943-8141}, abstract = {OBJECTIVE: To explore the risk factors for early clinical recurrence of inflammatory bowel disease (IBD) after fecal microbiota transplantation (FMT).<br><br>METHODS: A retrospective study was conducted on 192 patients with IBD who received FMT treatment in the Colorectal Disease Specialty/Intestinal Microecology Treatment Center of the Tenth People's Hospital Affiliated to Tongji University from February 2017 to June 2020. Univariate and multivariate logistic regression models were used to analyze the risk factors for early recurrence of inflammation. Feces from all participants were collected to extract the total bacterial genomic DNA. The V6-8 regions of the bacterial 16S rDNA gene were amplified by polymerase chain reaction (PCR), the PCR products were detected by the denaturing gradient gel electrophoresis (DGGE) method, and the intestinal flora was analyzed by DNA fingerprinting. Stool samples from all patients were tested for 9 bacteria, white blood cells (WBC) and platelet (PLT) counts, as well as the erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level.<br><br>RESULTS: Of the 192 patients, 15 cases had inflammation recurrence during FMT and within one week after treatment, including 11 cases of ulcerative colitis (UC) and 4 cases of Crohn's disease (CD), with a total recurrence rate of 7.8%. High Mayo inflammatory activity score, Mayo endoscopic sub-item score (MES) =3 points, CRP>10 mg/L, anemia, albumin <30 g/L, absolute value of peripheral blood lymphocytes (PBL) <500/mm[3], and intolerance to enteral full nutrition were independent risk factors for recurrence during and after FMT in UC patients (P<0.05). Albumin <30 g/L and simultaneous use of immunosuppressive agents were associated with disease recurrence during and after FMT in CD patients. WBC, PLT, and CRP were all negatively correlated with Enterococcus (EC), and ESR was positively correlated with Saccharomyces boulardii (SB) (P<0.01).<br><br>CONCLUSION: The low recurrence rate of IBD after FMT indicates the safety of FMT, but this procedure should be cautiously used in patients with severe intestinal barrier dysfunction and/or severe intestinal dysfunction.}, }
@article {pmid34955896, year = {2021}, author = {Zhao, Z and Guo, Z and Yin, Z and Qiu, Y and Zhou, B}, title = {Gut Microbiota Was Involved in the Process of Liver Injury During Intra-Abdominal Hypertension.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {790182}, pmid = {34955896}, issn = {1664-042X}, abstract = {Background: Intestinal damage caused by intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) can lead to the ectopic gut microbiota, which can contribute to liver injury via portal veins. Therefore, it is speculated that gut microbiota disorder caused by IAH/ACS may result in liver injury. The relationship between gut microbiota and IAH/ACS-related liver injury was investigated in this study. Methods: A model of IAH was established in rats, and 16S rRNA sequencing was analyzed for gut microbiota in the feces of rats. The elimination of gut microbiota was completed by antibiotics gavage, and fecal microbiota transplantation (FMT) was used to change the composition of gut microbiota in rats. Results: In addition to the traditional cause of liver blood vessel compression, liver injury caused by IAH was also associated with gut microbiota dysbiosis. Gut microbiota clearance can relieve liver injury caused by IAH, while FMT from IAH-intervened rats can aggravate IAH-related liver injury. Conclusion: The gut microbiota was one of the most important factors contributing to the IAH-related liver injury, and the JNK/p38 signaling pathway was activated in this process.}, }
@article {pmid34955437, year = {2022}, author = {Aira, A and Arajol, C and Casals-Pascual, C and González-Suárez, B and Martí, S and Domínguez, M&#xc1; and Guardiola, J and Soriano, &#xc1; and , }, title = {Recommendations for stool donor selection for fecal microbiota transplant. Consensus document endorsed by the Catalan Society of Digestology, Catalan Society of Infectious diseases and Clinical Microbiology and the GEMBIOTA group from Spanish Society of Infectious Diseases and Clinical Microbiology.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {40}, number = {3}, pages = {142-146}, doi = {10.1016/j.eimce.2021.12.001}, pmid = {34955437}, issn = {2529-993X}, mesh = {*Clostridium Infections/microbiology/therapy ; *Communicable Diseases ; Consensus ; Donor Selection ; Fecal Microbiota Transplantation/methods ; Humans ; }, abstract = {Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimise the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluña with the aim of establishing recommendations for the selection of the fecal microbiota donor.}, }
@article {pmid34950432, year = {2021}, author = {Shaikh, DH and Patel, H and Munshi, R and Sun, H and Mehershahi, S and Baiomi, A and Alemam, A and Pirzada, U and Nawaz, I and Naher, K and Hanumanthu, S and Nayudu, S}, title = {Patients with Clostridium difficile infection and prior appendectomy may be prone to worse outcomes.}, journal = {World journal of gastrointestinal surgery}, volume = {13}, number = {11}, pages = {1436-1447}, pmid = {34950432}, issn = {1948-9366}, abstract = {BACKGROUND: Clostridium difficile infection (CDI) occurs due to a dysbiosis in the colon. The appendix is considered a 'safe house' for gut microbiota and may help repopulate gut flora of patients with CDI.<br><br>AIM: To study the impact of prior appendectomy on the severity and outcomes of CDI.<br><br>METHODS: We retrospectively reviewed data of 1580 patients with CDI, admitted to our hospital between 2008 to 2018. Patients were grouped based on the presence or absence of the appendix. The primary aim was to (1) assess all-cause mortality and (2) the severity of CDI. Severity was defined as per the Infectious Diseases Society of America criteria. Logistic regression, and propensity score analysis using inverse probability of treatment weights (IPTW) was performed.<br><br>RESULTS: Of the 1580 patients, 12.5% had a history of appendectomy. There was no statistical difference in mortality between patients with a prior appendectomy or without (13.7% vs 14%, P = 0.877). However, a history of appendectomy affected the severity of CDI [odds ratio (OR) = 1.32, 95% confidence interval: 1.01-1.75]. On IPTW, this association remained significant (OR = 1.59, P < 0.05). On multivariable analysis of secondary outcomes, prior appendectomy was also associated with toxic megacolon (OR = 5.37, P < 0.05) and colectomy (OR = 2.77, P < 0.05).<br><br>CONCLUSION: Prior appendectomy may affect the severity of CDI, development of toxic megacolon and the eventual need for colectomy. Since treatment of CDI is governed by its severity, stronger antibiotic regimens or earlier use of fecal microbiota transplant may be a viable option for patients with prior appendectomy.}, }
@article {pmid34950418, year = {2021}, author = {Xu, B and Qin, W and Xu, Y and Yang, W and Chen, Y and Huang, J and Zhao, J and Ma, L}, title = {Dietary Quercetin Supplementation Attenuates Diarrhea and Intestinal Damage by Regulating Gut Microbiota in Weanling Piglets.}, journal = {Oxidative medicine and cellular longevity}, volume = {2021}, number = {}, pages = {6221012}, pmid = {34950418}, issn = {1942-0994}, mesh = {Animal Feed/analysis ; Animals ; Antioxidants/administration &amp; dosage ; Bacteria/classification/growth &amp; development ; Diarrhea/microbiology/pathology/*prevention &amp; control ; *Dietary Supplements ; Dysbiosis/microbiology/pathology/*prevention &amp; control ; Fecal Microbiota Transplantation/*methods ; Female ; *Gastrointestinal Microbiome ; Intestinal Diseases/microbiology/pathology/*prevention &amp; control ; Quercetin/*administration &amp; dosage ; Swine ; Weaning ; }, abstract = {Antioxidant polyphenols from plants are potential dietary supplementation to alleviate early weaning-induced intestinal disorders in piglets. Recent evidences showed polyphenol quercetin could reshape gut microbiota when it functioned as anti-inflammation or antioxidation agents in rodent models. However, the effect of dietary quercetin supplementation on intestinal disorders and gut microbiota of weanling piglets, along with the role of gut microbiota in this effect, both remain unclear. Here, we determined the quercetin's effect on attenuating diarrhea, intestinal damage, and redox imbalance, as well as the role of gut microbiota by transferring the quercetin-treated fecal microbiota to the recipient piglets. The results showed that dietary quercetin supplementation decreased piglets' fecal scores improved intestinal damage by increasing tight junction protein occludin, villus height, and villus height/crypt depth ratio but decreased crypt depth and intestinal epithelial apoptosis (TUNEL staining). Quercetin also increased antioxidant capacity indices, including total antioxidant capacity, catalase, and glutathione/oxidized glutathione disulfide but decreased oxidative metabolite malondialdehyde in the jejunum tissue. Fecal microbiota transplantation (FMT) from quercetin-treated piglets had comparable effects on improving intestinal damage and antioxidative capacity than dietary quercetin supplementation. Further analysis of gut microbiota using 16S rDNA sequencing showed that dietary quercetin supplementation or FMT shifted the structure and increased the diversity of gut microbiota. Especially, anaerobic trait and carbohydrate metabolism functions of gut microbiota were enriched after dietary quercetin supplementation and FMT, which may owe to the increased antioxidative capacity of intestine. Quercetin increased the relative abundances of Fibrobacteres, Akkermansia muciniphila, Clostridium butyricum, Clostridium celatum, and Prevotella copri but decreased the relative abundances of Proteobacteria, Lactobacillus coleohominis, and Ruminococcus bromii. Besides, quercetin-shifted bacteria and carbohydrate metabolites short chain fatty acids were significantly related to the indices of antioxidant capacity and intestinal integrity. Overall, dietary quercetin supplementation attenuated diarrhea and intestinal damage by enhancing the antioxidant capacity and regulating gut microbial structure and metabolism in piglets.}, }
@article {pmid34949826, year = {2022}, author = {Buffa, JA and Romano, KA and Copeland, MF and Cody, DB and Zhu, W and Galvez, R and Fu, X and Ward, K and Ferrell, M and Dai, HJ and Skye, S and Hu, P and Li, L and Parlov, M and McMillan, A and Wei, X and Nemet, I and Koeth, RA and Li, XS and Wang, Z and Sangwan, N and Hajjar, AM and Dwidar, M and Weeks, TL and Bergeron, N and Krauss, RM and Tang, WHW and Rey, FE and DiDonato, JA and Gogonea, V and Gerberick, GF and Garcia-Garcia, JC and Hazen, SL}, title = {The microbial gbu gene cluster links cardiovascular disease risk associated with red meat consumption to microbiota L-carnitine catabolism.}, journal = {Nature microbiology}, volume = {7}, number = {1}, pages = {73-86}, pmid = {34949826}, issn = {2058-5276}, support = {P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R01 HL126827/HL/NHLBI NIH HHS/United States ; R01 HL106003/HL/NHLBI NIH HHS/United States ; UL1 TR000004/TR/NCATS NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cardiovascular Diseases/blood/*genetics ; Carnitine/*blood/*metabolism ; Clostridiales/genetics/metabolism ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Genes, Bacterial/*genetics ; Germ-Free Life ; Humans ; Methylamines/metabolism ; Mice ; Mice, Inbred C57BL ; *Multigene Family ; Observational Studies as Topic ; *Red Meat ; }, abstract = {The heightened cardiovascular disease (CVD) risk observed among omnivores is thought to be linked, in part, to gut microbiota-dependent generation of trimethylamine-N-oxide (TMAO) from L-carnitine, a nutrient abundant in red meat. Gut microbial transformation of L-carnitine into trimethylamine (TMA), the precursor of TMAO, occurs via the intermediate γ-butyrobetaine (γBB). However, the interrelationship of γBB, red meat ingestion and CVD risks, as well as the gut microbial genes responsible for the transformation of γBB to TMA, are unclear. In the present study, we show that plasma γBB levels in individuals from a clinical cohort (n = 2,918) are strongly associated with incident CVD event risks. Culture of human faecal samples and microbial transplantation studies in gnotobiotic mice with defined synthetic communities showed that the introduction of Emergencia timonensis, a human gut microbe that can metabolize γBB into TMA, is sufficient to complete the carnitine → γBB → TMA transformation, elevate TMAO levels and enhance thrombosis potential in recipients after arterial injury. RNA-sequencing analyses of E. timonensis identified a six-gene cluster, herein named the γBB utilization (gbu) gene cluster, which is upregulated in response to γBB. Combinatorial cloning and functional studies identified four genes (gbuA, gbuB, gbuC and gbuE) that are necessary and sufficient to recapitulate the conversion of γBB to TMA when coexpressed in Escherichia coli. Finally, reanalysis of samples (n = 113) from a clinical, randomized diet, intervention study showed that the abundance of faecal gbuA correlates with plasma TMAO and a red meat-rich diet. Our findings reveal a microbial gene cluster that is critical to dietary carnitine → γBB → TMA → TMAO transformation in hosts and contributes to CVD risk.}, }
@article {pmid34949194, year = {2021}, author = {Wu, Y and Zhang, Y and Xie, B and Abdelgawad, A and Chen, X and Han, M and Shang, Y and Yuan, S and Zhang, J}, title = {RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.}, journal = {Journal of neuroinflammation}, volume = {18}, number = {1}, pages = {300}, pmid = {34949194}, issn = {1742-2094}, support = {82071480//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Atrial Natriuretic Factor/*pharmacology ; Brain-Gut Axis/*drug effects ; Cognitive Dysfunction/*chemically induced/psychology ; Endotoxins/*antagonists &amp; inhibitors/toxicity ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Inflammation Mediators ; Injections, Intraperitoneal ; Lipopolysaccharides/antagonists &amp; inhibitors ; Male ; Mice ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/microbiology ; Recombinant Proteins ; Vagotomy ; Vagus Nerve/*microbiology ; }, abstract = {BACKGROUND: Atrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is to assess the effect of ANP on bacterial lipopolysaccharide (LPS)-induced endotoxemia-derived neuroinflammation and cognitive impairment.<br><br>METHODS: LPS (5&#xa0;mg/kg) was given intraperitoneally to mice. Recombinant human ANP (rhANP) (1.0&#xa0;mg/kg) was injected intravenously 24&#xa0;h before and/or 10&#xa0;min after LPS injection. Subdiaphragmatic vagotomy (SDV) was performed 14&#xa0;days before LPS injection or 28&#xa0;days before fecal microbiota transplantation (FMT). ANA-12 (0.5&#xa0;mg/kg) was administrated intraperitoneally 30&#xa0;min prior to rhANP treatment.<br><br>RESULTS: LPS (5.0&#xa0;mg/kg) induced remarkable splenomegaly and an increase in the plasma cytokines at 24&#xa0;h after LPS injection. There were positive correlations between spleen weight and plasma cytokines levels. LPS also led to increased protein levels of ionized calcium-binding adaptor molecule (iba)-1, cytokines and inducible nitric oxide synthase (iNOS) in the hippocampus. LPS impaired the natural and learned behavior, as demonstrated by an increase in the latency to eat the food in the buried food test and a decrease in the number of entries and duration in the novel arm in the Y maze test. Combined prophylactic and therapeutic treatment with rhANP reversed LPS-induced splenomegaly, hippocampal and peripheral inflammation as well as cognitive impairment. However, rhANP could not further enhance the protective effects of SDV on hippocampal and peripheral inflammation. We further found that PGF mice transplanted with fecal bacteria from rhANP-treated endotoxemia mice alleviated the decreased protein levels of hippocampal polyclonal phosphorylated tyrosine&#xa0;kinase&#xa0;receptor&#xa0;B (p-TrkB), brain-derived neurotrophic factor (BDNF) and cognitive impairment, which was abolished by SDV. Moreover, TrkB/BDNF signaling inhibitor ANA-12 abolished the improving effects of rhANP on LPS-induced cognitive impairment.<br><br>CONCLUSIONS: Our results suggest that rhANP could mitigate LPS-induced hippocampal inflammation and cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.}, }
@article {pmid34946163, year = {2021}, author = {Kosaka, S and Nadatani, Y and Higashimori, A and Otani, K and Fujimoto, K and Nagata, Y and Ominami, M and Fukunaga, S and Hosomi, S and Kamata, N and Tanaka, F and Nagami, Y and Taira, K and Imoto, S and Uematsu, S and Watanabe, T and Fujiwara, Y}, title = {Ovariectomy-Induced Dysbiosis May Have a Minor Effect on Bone in Mice.}, journal = {Microorganisms}, volume = {9}, number = {12}, pages = {}, pmid = {34946163}, issn = {2076-2607}, support = {17K15962//JSPS KAKENHI/ ; }, abstract = {We determined the bone mineral density (BMD) and the expression of serum bone formation marker (procollagen type I N-terminal propeptide: PINP) and bone resorption marker (C-terminal telopeptide of collagen: CTX) by ELISA to evaluate ovariectomy-induced osteoporosis in ovariectomized (OVX) mice. The intestinal microbiota of the mice was assessed using 16S rRNA gene sequencing. OVX mice exhibited a lower BMD of 87% with higher serum levels of CTX and PINP compared to sham-operated (sham) mice. The cecum microbiome of OVX mice showed lower bacterial diversity than that of sham mice. TNFα mRNA levels in the colon were 1.6 times higher, and zonula occludens-1 mRNA and protein expression were lower in OVX mice than in sham mice, suggesting that ovariectomy induced inflammation and increased intestinal permeability. Next, we used antibiotic treatment followed by fecal microbiota transplantation (FMT) to remodel the gut microbiota in the OVX mice. A decrease in PINP was observed in antibiotic-treated mice, while there was no change in BMD or CTX between mice with and without antibiotic treatment. Oral transplantation of the luminal cecal content of OVX or sham mice to antibiotic-treated mice did not affect the BMD or PINP and CTX expression. Additionally, transplantation of the luminal contents of OVX or sham mice to antibiotic-treated OVX mice had similar effects on BMD, PINP, and CTX. In conclusion, although ovariectomy induces dysbiosis in the colon, the changes in the gut microbiota may only have a minor role in ovariectomy-induced osteoporosis.}, }
@article {pmid34946148, year = {2021}, author = {Valeri, F and Dos Santos Guilherme, M and He, F and Stoye, NM and Schwiertz, A and Endres, K}, title = {Impact of the Age of Cecal Material Transfer Donors on Alzheimer's Disease Pathology in 5xFAD Mice.}, journal = {Microorganisms}, volume = {9}, number = {12}, pages = {}, pmid = {34946148}, issn = {2076-2607}, support = {nn//Alfons Geib foundation for dementia research/ ; BIS_04//Boehringer Ingelheim Fonds/ ; nn//Dr.Georg Scheuing foundation/ ; }, abstract = {Alzheimer's disease is a progressive neurodegenerative disorder affecting around 30 million patients worldwide. The predominant sporadic variant remains enigmatic as the underlying cause has still not been identified. Since efficient therapeutic treatments are still lacking, the microbiome and its manipulation have been considered as a new, innovative approach. 5xFAD Alzheimer's disease model mice were subjected to one-time fecal material transfer after antibiotics-treatment using two types of inoculation: material derived from the caecum of age-matched (young) wild type mice or from middle aged, 1 year old (old) wild type mice. Mice were profiled after transfer for physiological parameters, microbiome, behavioral tasks, and amyloid deposition. A single time transfer of cecal material from the older donor group established an aged phenotype in the recipient animals as indicated by elevated cultivatable fecal Enterobacteriaceae and Lactobacillaceae representative bacteria, a decreased Firmicutes amount as assessed by qPCR, and by increased levels of serum LPS binding protein. While behavioral deficits were not accelerated, single brain regions (prefrontal cortex and dentate gyrus) showed higher plaque load after transfer of material from older animals. We could demonstrate that the age of the donor of cecal material might affect early pathological hallmarks of Alzheimer's disease. This could be relevant when considering new microbiome-based therapies for this devastating disorder.}, }
@article {pmid34946139, year = {2021}, author = {Broecker, F and Moelling, K}, title = {The Roles of the Virome in Cancer.}, journal = {Microorganisms}, volume = {9}, number = {12}, pages = {}, pmid = {34946139}, issn = {2076-2607}, abstract = {Viral infections as well as changes in the composition of the intestinal microbiota and virome have been linked to cancer. Moreover, the success of cancer immunotherapy with checkpoint inhibitors has been correlated with the intestinal microbial composition of patients. The transfer of feces-which contain mainly bacteria and their viruses (phages)-from immunotherapy responders to non-responders, known as fecal microbiota transplantation (FMT), has been shown to be able to convert some non-responders to responders. Since phages may also increase the response to immunotherapy, for example by inducing T cells cross-reacting with cancer antigens, modulating phage populations may provide a new avenue to improve immunotherapy responsiveness. In this review, we summarize the current knowledge on the human virome and its links to cancer, and discuss the potential utility of bacteriophages in increasing the responder rate for cancer immunotherapy.}, }
@article {pmid34945118, year = {2021}, author = {Popa, D and Neamtu, B and Mihalache, M and Boicean, A and Banciu, A and Banciu, DD and Moga, DFC and Birlutiu, V}, title = {Fecal Microbiota Transplant in Severe and Non-Severe Clostridioides difficile Infection. Is There a Role of FMT in Primary Severe CDI?.}, journal = {Journal of clinical medicine}, volume = {10}, number = {24}, pages = {}, pmid = {34945118}, issn = {2077-0383}, support = {LBUS-IRG-2021-07//Lucian Blaga University of Sibiu &amp; Hasso Plattner Foundation/ ; }, abstract = {BACKGROUND: Faecal microbiota transplant (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) with cure rates ranging between 85 and 92%. The FMT role for primary Clostridioides difficile infection (CDI) has yet to be settled because of limited data and small-sample studies presented in the current literature. Our study goals were to report the risk factors and the risk of recurrence after FMT for each CDI episode (first, second, and third) and to explore if there is a role of FMT in primary severe CDI.<br><br>METHODS: We conducted a retrospective study to analyze the clinical characteristics and the outcomes of 96 FMT patients with a prior 10 day course of antibiotic treatment in the medical records, of which 71 patients with recurrent CDI and 25 patients with a primary CDI.<br><br>RESULTS: The overall primary cure rate in our study was 88.5% and the primary cure rate for the severe forms was 85.7%. The data analysis revealed 5.25%, 15.15%, and 27.3% FMT recurrence rates for primary, secondary, and tertiary severe CDI. The risk of recurrence was significantly associated with FMT after the second and the third CDI severe episodes (p < 0.05), but not with FMT after the first severe CDI episode.<br><br>CONCLUSIONS: This study brings new data in supporting the FMT role in CDI treatment, including the primary severe CDI, however, further prospective and controlled studies on larger cohorts should be performed in this respect.}, }
@article {pmid34941392, year = {2021}, author = {Spencer, CN and McQuade, JL and Gopalakrishnan, V and McCulloch, JA and Vetizou, M and Cogdill, AP and Khan, MAW and Zhang, X and White, MG and Peterson, CB and Wong, MC and Morad, G and Rodgers, T and Badger, JH and Helmink, BA and Andrews, MC and Rodrigues, RR and Morgun, A and Kim, YS and Roszik, J and Hoffman, KL and Zheng, J and Zhou, Y and Medik, YB and Kahn, LM and Johnson, S and Hudgens, CW and Wani, K and Gaudreau, PO and Harris, AL and Jamal, MA and Baruch, EN and Perez-Guijarro, E and Day, CP and Merlino, G and Pazdrak, B and Lochmann, BS and Szczepaniak-Sloane, RA and Arora, R and Anderson, J and Zobniw, CM and Posada, E and Sirmans, E and Simon, J and Haydu, LE and Burton, EM and Wang, L and Dang, M and Clise-Dwyer, K and Schneider, S and Chapman, T and Anang, NAS and Duncan, S and Toker, J and Malke, JC and Glitza, IC and Amaria, RN and Tawbi, HA and Diab, A and Wong, MK and Patel, SP and Woodman, SE and Davies, MA and Ross, MI and Gershenwald, JE and Lee, JE and Hwu, P and Jensen, V and Samuels, Y and Straussman, R and Ajami, NJ and Nelson, KC and Nezi, L and Petrosino, JF and Futreal, PA and Lazar, AJ and Hu, J and Jenq, RR and Tetzlaff, MT and Yan, Y and Garrett, WS and Huttenhower, C and Sharma, P and Watowich, SS and Allison, JP and Cohen, L and Trinchieri, G and Daniel, CR and Wargo, JA}, title = {Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response.}, journal = {Science (New York, N.Y.)}, volume = {374}, number = {6575}, pages = {1632-1640}, pmid = {34941392}, issn = {1095-9203}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P30 ES030285/ES/NIEHS NIH HHS/United States ; R01 CA219896/CA/NCI NIH HHS/United States ; R01 AI133822/AI/NIAID NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; F32 CA260769/CA/NCI NIH HHS/United States ; R01 AI109294/AI/NIAID NIH HHS/United States ; R25 CA203650/CA/NCI NIH HHS/United States ; 27140/CRUK_/Cancer Research UK/United Kingdom ; R01 HL124112/HL/NHLBI NIH HHS/United States ; R01 AI143886/AI/NIAID NIH HHS/United States ; P50 CA221703/CA/NCI NIH HHS/United States ; P30 CA013696/CA/NCI NIH HHS/United States ; R56 AI109294/AI/NIAID NIH HHS/United States ; U54 CA224070/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cohort Studies ; *Dietary Fiber ; Fatty Acids, Volatile/analysis ; Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Immunotherapy ; Male ; Melanoma/immunology/microbiology/*therapy ; Melanoma, Experimental/immunology/microbiology/therapy ; Mice ; Mice, Inbred C57BL ; *Probiotics ; Progression-Free Survival ; T-Lymphocytes ; }, abstract = {Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti–programmed cell death 1 (anti–PD-1)–based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-γ–positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.}, }
@article {pmid34938813, year = {2021}, author = {Wang, S and Chen, H and Wen, X and Mu, J and Sun, M and Song, X and Liu, B and Chen, J and Fan, X}, title = {The Efficacy of Fecal Microbiota Transplantation in Experimental Autoimmune Encephalomyelitis: Transcriptome and Gut Microbiota Profiling.}, journal = {Journal of immunology research}, volume = {2021}, number = {}, pages = {4400428}, pmid = {34938813}, issn = {2314-7156}, mesh = {Animals ; Biomarkers ; Disease Management ; Disease Models, Animal ; Disease Susceptibility/immunology ; Encephalomyelitis, Autoimmune, Experimental/diagnosis/*etiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Intestinal Mucosa/metabolism/pathology ; Metagenomics/methods ; Mice ; Phylogeny ; RNA, Ribosomal, 16S ; Severity of Illness Index ; Spinal Cord/immunology/metabolism/pathology ; *Transcriptome ; Treatment Outcome ; }, abstract = {OBJECTIVE: To study the protective effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and reveal its potential intestinal microflora-dependent mechanism through analyses of the intestinal microbiota and spinal cord transcriptome in mice.<br><br>METHOD: We measured the severity of disease by clinical EAE scores and H&amp;E staining. Gut microbiota alteration in the gut and differentially expressed genes (DEGs) in the spinal cord were analyzed through 16S rRNA and transcriptome sequencing. Finally, we analyzed associations between the relative abundance of intestinal microbiota constituents and DEGs.<br><br>RESULTS: We observed that clinical EAE scores were lower in the EAE+FMT group than in the EAE group. Meanwhile, mice in the EAE+FMT group also had a lower number of infiltrating cells. The results of 16S rRNA sequence analysis showed that FMT increased the relative abundance of Firmicutes and Proteobacteria and reduced the abundance of Bacteroides and Actinobacteria. Meanwhile, FMT could modulate gut microbiota balance, especially via increasing the relative abundance of g_Adlercreutzia, g_Sutterella, g_Prevotella_9, and g_Tyzzerella_3 and decreasing the relative abundance of g_Turicibacter. Next, we analyzed the transcriptome of mouse spinal cord tissue and found that 1476 genes were differentially expressed between the EAE and FMT groups. The analysis of these genes showed that FMT mainly participated in the inflammatory response. Correlation analysis between gut microbes and transcriptome revealed that the relative abundance of Adlercreutzia was correlated with the expression of inflammation-related genes negatively, including Casp6, IL1RL2 (IL-36R), IL-17RA, TNF, CCL3, CCR5, and CCL8, and correlated with the expression of neuroprotection-related genes positively, including Snap25, Edil3, Nrn1, Cpeb3, and Gpr37.<br><br>CONCLUSION: Altogether, FMT may selectively regulate gene expression to improve inflammation and maintain the stability of the intestinal environment in a gut microbiota-dependent manner.}, }
@article {pmid34934429, year = {2022}, author = {Zhang, T and Wang, T and Chen, X and Zhao, Z and Chen, Z}, title = {Gut microbiota relieves inflammation in the substantia nigra of chronic Parkinson's disease by protecting the function of dopamine neurons.}, journal = {Experimental and therapeutic medicine}, volume = {23}, number = {1}, pages = {52}, pmid = {34934429}, issn = {1792-1015}, abstract = {The composition of the intestinal flora of patients with Parkinson's disease (PD) can change. However, whether reshaping the gut microbial composition can treat PD remains to be seen. The present study evaluated the effect of intestinal flora in the treatment of PD in a C57BL/6 mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Chronic, low-dose, MPTP-treated mice exhibited upregulated gene expression levels of TNF-α and IL-1β in the substantia nigra (SN) of the mice, and induced intestinal microbial disorders. This indicated that the chronic low-dose MPTP model could be used to evaluate the progress of early intestinal pathology and intestinal flora imbalance in PD. After transplantation of faecal bacteria to MPTP-induced PD mice, the level of inflammation in the SN of the mice was reduced, and motor dysfunction was alleviated. Notably, faecal microbiota transplantation (FMT) upregulated the abundance of Blautia but downregulated Anaerostipes, Bifidobacterium, ASF356 and Ruminococcus in the gut of PD mice. In addition, FMT reduced the activation of microglia and astrocytes in the SN and reduced the expression levels of GSK3β, IL-1β, inducible nitric oxide synthase and phosphorylated PTEN in the SN. Overall, the present study demonstrated that gut microbial dysfunction is associated with the pathogenesis of PD, and that FMT can protect PD mice by inhibiting neuroinflammation.}, }
@article {pmid34933877, year = {2021}, author = {Hofmeister, M and Clement, F and Patten, S and Li, J and Dowsett, LE and Farkas, B and Mastikhina, L and Egunsola, O and Diaz, R and Cooke, NCA and Taylor, VH}, title = {The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis.}, journal = {CMAJ open}, volume = {9}, number = {4}, pages = {E1195-E1204}, pmid = {34933877}, issn = {2291-0026}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Depression/*diet therapy/*microbiology ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Male ; Middle Aged ; Synbiotics/*administration &amp; dosage ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Despite their popularity, the efficacy of interventions targeting gut microbiota to improve depressive symptoms is unknown. Our objective is to summarize the effect of microbiome-targeting interventions on depressive symptoms.<br><br>METHODS: We conducted a systematic review and meta-analysis. We searched MEDLINE, Embase, PsycINFO, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews and the Cochrane Controlled Register of Trials from inception to Mar. 5, 2021. We included studies that evaluated probiotic, prebiotic, synbiotic, paraprobiotic or fecal microbiota transplant interventions in an adult population (age &#x2265; 18 yr) with an inactive or placebo comparator (defined by the absence of active intervention). Studies must have measured depressive symptoms with a validated scale, and used a randomized controlled trial study design. We conducted a random effects meta-analysis of change scores, using standardized mean difference as the measure of effect.<br><br>RESULTS: Sixty-two studies formed the final data set, with 50 included in the meta-analysis. Probiotic, prebiotic, and synbiotic interventions on depressive symptoms showed statistically significant benefits. In the single studies evaluating each of fecal microbiota transplant and paraprobiotic interventions, neither showed a statistically significant benefit.<br><br>INTERPRETATION: Despite promising findings of benefit of probiotic, prebiotic and synbiotic interventions for depressive symptoms in study populations, there is not yet strong enough evidence to favour inclusion of these interventions in treatment guidelines for depression. Critical questions about species administered, dosage and timing relative to other antidepressant medications remain to be answered.<br><br>STUDY REGISTRATION: PROSPERO no. 143178.}, }
@article {pmid34933425, year = {2021}, author = {Xia, QY and Lu, D and Zhang, JM and Wei, YC and Yang, MM and Yang, ZY and Cao, MB}, title = {[Intestinal flora polymorphisms with different lesional stages in an animal model of MAFLD].}, journal = {Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology}, volume = {29}, number = {11}, pages = {1069-1076}, doi = {10.3760/cma.j.cn501113-20200826-00478}, pmid = {34933425}, issn = {1007-3418}, support = {192102310049//Key Science and Technology Project of Henan Science and Technology Department/ ; }, mesh = {Animals ; Diet ; Diet, High-Fat ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Liver ; Mice ; Mice, Inbred C57BL ; *Non-alcoholic Fatty Liver Disease ; RNA, Ribosomal, 16S ; }, abstract = {Objective: To study the intestinal flora specific differences with different lesional stages of metabolic (disorder) associated fatty liver disease (MAFLD), namely simple steatosis and steatohepatitis, so as to provide a new direction for MAFLD-related intestinal flora transplantation and targeted therapy. Methods: Mice were fed with normal diet, methionine-choline deficient diet (MCD) and a high-fat high-fructose diet (HFHF) for 12 weeks to construct simple steatosis and steatohepatitis models. HE and Sirius scarlet staining was performed to observe the liver pathological changes. The qPCR method was used to evaluate inflammation and liver fibrosis factors. A fully automatic biochemical analyzer was used to detect changes in liver transaminase and blood lipids. 16S rRNA sequencing method was used to observe the intestinal flora differences in the feces of each group of mice. The comparison of means between two groups was performed by t-test, and the comparison of means between multiple groups was performed by one-way analysis of variance. Kruskal-Wallis rank sum test was used for non-normally distributed data. Results: NAFLD scores were determined with pathological sections (HE and Sirius scarlet staining) of mice liver, which showed that the inflammation and liver fibrosis scores of the MCD and HFHF groups were 2.12 ± 0.18 and 1.06 ± 0.24, and 2.22 ± 0.16 and 0.46 ± 0.10, respectively. The degree of liver inflammation and fibrosis was significantly higher in the MCD than the HFHF group (P < 0.001 and P < 0.01). Lipid deposition was higher in the HFHF than the MCD group (P < 0.001), and the scores were 2.36 ± 0.17 and 1.60 ± 0.24 respectively. Simultaneously, the inflammatory [tumor necrosis factor-A (TNF-a), chemokine factor-2 (CXCL-2)] and hepatic fibrosis indicators [vascular smooth muscle actin alpha (a-SMA) and connective tissue growth factor (CTGF)] had confirmed the above-mentioned results at the transcription level. Moreover, the intestinal flora diversity was reduced (P < 0.05) in the MCD group than the HFHF group, and the Simpson and Shannon index were 0.31 ± 0.10 and 0.42 ± 0.05, and 2.03 ± 0.33 and 1.70 ± 0.28, respectively, and the differences were significant between different intestinal flora groups. The levels of Desulfovibrio, Odoribacter, and Roseburia flora were significantly increased in the HFHF than the MCD group, and the levels of Faecalibaculum, Parasutterella, Alipis, Butyricimonas_virosa, Turicibacter_sp, and Romboutsia_ilealis were significantly increased in the MCD than the HFHF group, and the difference was statistically significant (P < 0.05). Conclusion: There are significant differences in intestinal flora diversity between simple steatosis and steatohepatitis models. Therefore, clarifying the difference between the two may provide a new direction for the stage manner treatment of MAFLD.}, }
@article {pmid34932298, year = {2021}, author = {Katasonov, AB}, title = {[Gut microbiome as a therapeutic target in the treatment of depression and anxiety].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {121}, number = {11}, pages = {129-135}, doi = {10.17116/jnevro2021121111129}, pmid = {34932298}, issn = {1997-7298}, mesh = {Anxiety/drug therapy ; Depression/drug therapy ; Dysbiosis/drug therapy ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; }, abstract = {There is a bi-directional connection between the gut microbiome and the brain. Changes in the composition of the microbiome affect emotions, behavior, and the stress response involved in the pathogenesis of depression. Depression and anxiety are often associated with dysbiosis and inflammatory bowel disease. Dysbiosis enhances stress response and low-grade systemic inflammation, and vice versa. This vicious circle may be responsible for the formation of depression. Antidepressants therapy should be accompanied by the elimination of dysbiosis. For these purposes diet, prebiotics, probiotics and faecal microbiota transplantation can be used. The advantages and disadvantages of each method are considered. The manipulation of microbiome composition has been shown to have great therapeutic potential in the treatment of depression and anxiety.}, }
@article {pmid34931881, year = {2021}, author = {Chen, X and Wu, Q and Gao, X and Wang, H and Zhu, J and Xia, G and He, Y and Song, W and Xu, K}, title = {Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic Stroke.}, journal = {mSystems}, volume = {6}, number = {6}, pages = {e0130421}, pmid = {34931881}, issn = {2379-5077}, support = {201904010091//Science and Technology Program of Guangzhou/ ; 2018M630967//China Postdoctoral Science Foundation/ ; NSFC31800415//National Natural Science Foundation of China (NSFC)/ ; NSFC82022044//National Natural Science Foundation of China (NSFC)/ ; }, abstract = {Type 2 diabetes (T2D) is an independent risk factor for acute ischemic stroke (AIS), but the underlying mechanisms remain elusive. Because the gut microbiota plays a causal role in both T2D and AIS, we wondered whether gut dysbiosis in T2D aggravates stroke progression. We recruited 35 T2D, 90 AIS, 60 AIS with T2D (AIS_T2D) patients, and 55 healthy controls and found that AIS and T2D had an additive effect on AIS_T2D patient gut dysbiosis by exhibiting the largest difference from the heathy controls. In addition, we found that the degree of gut dysbiosis associated with T2D was positively correlated with the National Institutes of Health Stroke Scale (NIHSS), modified Rankin score (mRS), and Essen stroke risk score in patients with AIS, including AIS and AIS_T2D patients. Compared with mice colonized with gut microbiota from healthy controls poststroke modeling, germfree (GF) mice colonized with gut microbiota from T2D patients showed exacerbated cerebral injury and impaired gut barrier function. Specifically, exacerbated brain injury and gut barrier dysfunction in T2D-treated GF mice were significantly associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. Our study showed that T2D and AIS have an additive effect on AIS_T2D patient gut microbiota dysbiosis. T2D-associated gut microbiota dysbiosis is associated with stroke severity in AIS patients and aggravates stroke progression in mice. IMPORTANCE We demonstrated an additive effect of type 2 diabetes (T2D) and acute ischemic stroke (AIS) on AIS with T2D (AIS_T2D) patient gut microbiota dysbiosis, and gut dysbiosis associated with T2D was positively correlated with stroke severity in AIS patients. Through animal experiments, we found that cerebral injury was exacerbated by fecal microbiota transplantation from T2D patients compared with that from healthy controls, which was associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. This study provided a novel view that links T2D and AIS through gut microbial dysbiosis.}, }
@article {pmid34931478, year = {2022}, author = {Mashiah, J and Karady, T and Fliss-Isakov, N and Sprecher, E and Slodownik, D and Artzi, O and Samuelov, L and Ellenbogen, E and Godneva, A and Segal, E and Maharshak, N}, title = {Clinical efficacy of fecal microbial transplantation treatment in adults with moderate-to-severe atopic dermatitis.}, journal = {Immunity, inflammation and disease}, volume = {10}, number = {3}, pages = {e570}, pmid = {34931478}, issn = {2050-4527}, mesh = {Adult ; *Dermatitis, Atopic/drug therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a remitting relapsing chronic eczematous pruritic disease. Several studies suggest that gut microbiota may influence AD by immune system regulation.<br><br>METHODS: We performed the first in-human efficacy and safety assessment of fecal microbiota transplantation (FMT) for AD adult patients. All patients received 2 placebo transplantations followed by 4 FMTs each 2 weeks apart. AD severity and fecal microbiome profile were evaluated by the Scoring Atopic Dermatitis Score (SCORAD), the weekly frequency of topical corticosteroids usage, and gut microbiota metagenomic analysis, at the study beginning, before every FMT, and 1-8 months after the last FMT.<br><br>RESULTS: Nine patients completed the study protocol. There was no significant change in the SCORAD score following the two placebo transplants. The average SCORAD score significantly decreased from baseline at Weeks 4-12 (before and 2 weeks after 4 times of FMT) (59.2&#x2009;&#xb1;&#x2009;34.9%, Wilcoxon p&#x2009;=&#x2009;.011), 50% and 75% decrease was achieved by 7 (77%) and 4 (44%) patients, respectively. At Week 18 (8 weeks after the last FMT) the average SCORAD score decreased from baseline at Week 4 (85.5&#x2009;&#xb1;&#x2009;8.4%, Wilcoxon p&#x2009;=&#x2009;.018), 50% and 75% decrease was achieved by 7 (77%) and 6 (66.7%) patients respectively. Weekly topical corticosteroids usage was diminished during the study and follow-up period as well. Two patients had a quick relapse and were switched to a different treatment. Two patients developed exacerbations alleviated after an additional fifth FMT. Metagenomic analysis of the fecal microbiota of patients and donors showed bacterial strains transmission from donors to patients. No adverse events were recorded during the study and follow-up period.<br><br>CONCLUSIONS: FMT may be a safe and effective therapeutic intervention for AD patients, associated with transfer of specific microbial species from the donors to the patients. Further studies are required to reconfirm these results.}, }
@article {pmid34930601, year = {2022}, author = {Huang, W and Yan, Y and Wu, M and Hu, J and Zhao, J and Chen, X and Liu, W and Liu, K and Li, C}, title = {Preoperative fasting confers protection against intestinal ischaemia/reperfusion injury by modulating gut microbiota and their metabolites in a mouse model.}, journal = {British journal of anaesthesia}, volume = {128}, number = {3}, pages = {501-512}, doi = {10.1016/j.bja.2021.11.025}, pmid = {34930601}, issn = {1471-6771}, mesh = {Animals ; Apoptosis/physiology ; Disease Models, Animal ; Fasting/*metabolism ; Gastrointestinal Microbiome/*physiology ; Glucose/metabolism ; Mice ; Oleic Acids/pharmacology ; Oxygen/metabolism ; Preoperative Period ; Reperfusion Injury/drug therapy/*metabolism/*physiopathology ; }, abstract = {BACKGROUND: Intestinal ischaemia/reperfusion (I/R) injury is a grave surgical event with high morbidity and mortality. Preoperative fasting might confer protection against intestinal I/R injury by altering the composition of gut microbiota and their respective metabolites.<br><br>METHODS: An intestinal I/R mouse model was established and subjected to preoperative fasting for 24 h or fed ad libitum. Intestinal I/R injury was assessed using histological examination and survival analysis. Faecal samples were collected for 16S rDNA sequencing and metabolomic analysis. Faecal transplantation of fasted and non-fasted mice and humans was conducted to evaluate the effects of gut microbiota on intestinal I/R. Murine small intestinal cells wecre subjected to oxygen and glucose deprivation/reoxygenation as an in&#xa0;vitro I/R model.<br><br>RESULTS: Preoperative fasting protected against intestinal I/R injury and improved survival in mice (P<0.001). In addition, 16S rDNA sequencing revealed that preoperative fasting increased the diversity and restructured the composition of the gut microbiota after intestinal I/R. Mice that received microbiota from fasted mice and humans showed less intestinal damage than those that received microbiota from fed subjects. Metabolomic analysis showed that the profiles of gut microbial metabolites differed between fasted and fed groups. Specifically, the concentration of petroselinic acid was significantly higher in the fasted group (P=0.009). Treatment of intestinal I/R mice with petroselinic acid alleviated intestinal injury in&#xa0;vivo and decreased cell apoptosis by mediating AMP-activated protein kinase-mammalian target of rapamycin-P70S6K signaling in&#xa0;vitro.<br><br>CONCLUSIONS: Preoperative fasting protected against intestinal I/R injury by modulating gut microbiota and petroselinic acid, suggesting a novel therapeutic strategy.}, }
@article {pmid34927757, year = {2021}, author = {Nee, J and Lembo, A}, title = {Review Article: Current and future treatment approaches for IBS with diarrhoea (IBS-D) and IBS mixed pattern (IBS-M).}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {54 Suppl 1}, number = {}, pages = {S63-S74}, doi = {10.1111/apt.16625}, pmid = {34927757}, issn = {1365-2036}, mesh = {Constipation/drug therapy/therapy ; Diarrhea/drug therapy ; Gastrointestinal Agents/therapeutic use ; Humans ; *Irritable Bowel Syndrome/drug therapy/therapy ; Rifaximin/therapeutic use ; }, abstract = {BACKGROUND: Irritable bowel syndrome-diarrhoea (IBS-D) and IBS-mixed stool pattern (IBS-M) are disorders of gut-brain interaction characterised by abdominal pain associated with diarrhoea or both diarrhoea and constipation respectively. The pathophysiology of IBS-D/M is multifactorial and not completely understood; thus, treatment is aimed at multiple mechanisms such as altering gut microbiota, visceral hypersensitivity, intestinal permeability, gut-brain interaction and psychological strategies.<br><br>AIM: The goal of this article was to provide an up-to-date review of the current evidence for both non-pharmacological and pharmacological treatment options in IBS-D and IBS-M. Future treatments for IBS-D and IBS-M will also be discussed.<br><br>METHODS: Medline and Embase database searches (through April 30 2021) to identify clinical studies in subjects with IBS-D in which dietary modification, alternative treatments (probiotics, acupuncture, exercise) as well as FDA-approved medications were used.<br><br>RESULTS: Dietary modification is often the first line of therapy. Furthermore, lifestyle treatments include complementary alternative medications (CAM), probiotics and peppermint oil are useful adjuncts but have not specifically been described in IBS-D/M. Evidence strongly supports psychotherapy in the treatment of IBS. Beyond over-the counter anti-diarrhoeals, anti-spasmodics and anti-depressants, pharmacological treatment now includes treating for bile acid malabsorption and the FDA-approved medications rifaximin, eluxadoline and alosetron.<br><br>CONCLUSIONS: The treatment of IBS-D/M ideally involves a multidisciplinary approach of primary care, gastroenterologist and psychologist. Treatment often involves both non-pharmacological and pharmacological therapies. Future therapies may include faecal microbial transplant, Crofelemer and serotonin antagonists, but further studies are needed.}, }
@article {pmid34926663, year = {2021}, author = {Zhang, Y and Xue, X and Su, S and Zhou, H and Jin, Y and Shi, Y and Lin, J and Wang, J and Li, X and Yang, G and Philpott, JR and Liang, J}, title = {Patients and physicians' attitudes change on fecal microbiota transplantation for inflammatory bowel disease over the past 3 years.}, journal = {Annals of translational medicine}, volume = {9}, number = {21}, pages = {1619}, pmid = {34926663}, issn = {2305-5839}, abstract = {BACKGROUND: In the past 3 years, increasing data and experience has become available regarding fecal microbiota transplantation (FMT) for the treatment of inflammatory bowel disease (IBD). However, how this increase in knowledge has impacted the attitudes of patients and physicians is largely unknown. This study aimed to investigate the change of patients' and physicians' attitudes towards FMT for IBD treatment.<br><br>METHODS: Questionnaires for patient and physician attitude on FMT for IBD were pilot-tested and developed. Patients and physicians from the same groups completed the questionnaires in 2016 and 2019, separately. The attitudes towards efficacy, adverse events, and methodological features of FMT in 2016 were compared with those in 2019.<br><br>RESULTS: A total of 1,255 questionnaires from 486 patients and 769 physicians were collected. Over the 3 years, an increased number of patients had heard of FMT and had similarly positive opinions towards using FMT for IBD therapy. Additionally, patients retained the tendency to overestimate the efficacy. The physicians' perceptions became closer to the findings reported in recent studies in 2019 compared with 2016. However, only a minority of patients and physicians understood the frequency required of FMT courses for induction of clinical remission. In particular, both patients and physicians underestimated the risk of mild adverse events and IBD flare.<br><br>CONCLUSIONS: Patients are receptive towards FMT as therapy for IBD but opportunity remains to improve understanding of benefit and potential risks. Physicians also demonstrated knowledge gaps in use of this therapy. Aligning patient preference and physician knowledge gap will lead to better education and facilitate the development of decision-making guidelines.}, }
@article {pmid34925385, year = {2021}, author = {Pan, Q and Guo, F and Huang, Y and Li, A and Chen, S and Chen, J and Liu, HF and Pan, Q}, title = {Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus: Novel Insights into Mechanisms and Promising Therapeutic Strategies.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {799788}, pmid = {34925385}, issn = {1664-3224}, mesh = {Animals ; Dysbiosis/*complications/*immunology ; Gastrointestinal Microbiome/*immunology ; Humans ; Lupus Erythematosus, Systemic/immunology/*microbiology ; }, abstract = {Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that was traditionally thought to be closely related to genetic and environmental risk factors. Although treatment options for SLE with hormones, immunosuppressants, and biologic drugs are now available, the rates of clinical response and functional remission of these drugs are still not satisfactory. Currently, emerging evidence suggests that gut microbiota dysbiosis may play crucial roles in the occurrence and development of SLE, and manipulation of targeting the gut microbiota holds great promises for the successful treatment of SLE. The possible mechanisms of gut microbiota dysbiosis in SLE have not yet been well identified to date, although they may include molecular mimicry, impaired intestinal barrier function and leaky gut, bacterial biofilms, intestinal specific pathogen infection, gender bias, intestinal epithelial cells autophagy, and extracellular vesicles and microRNAs. Potential therapies for modulating gut microbiota in SLE include oral antibiotic therapy, fecal microbiota transplantation, glucocorticoid therapy, regulation of intestinal epithelial cells autophagy, extracellular vesicle-derived miRNA therapy, mesenchymal stem cell therapy, and vaccination. This review summarizes novel insights into the mechanisms of microbiota dysbiosis in SLE and promising therapeutic strategies, which may help improve our understanding of the pathogenesis of SLE and provide novel therapies for SLE.}, }
@article {pmid34925349, year = {2021}, author = {Hao, H and Zhang, X and Tong, L and Liu, Q and Liang, X and Bu, Y and Gong, P and Liu, T and Zhang, L and Xia, Y and Ai, L and Yi, H}, title = {Effect of Extracellular Vesicles Derived From Lactobacillus plantarum Q7 on Gut Microbiota and Ulcerative Colitis in Mice.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {777147}, pmid = {34925349}, issn = {1664-3224}, mesh = {Animals ; Colitis, Ulcerative/chemically induced/immunology/microbiology/*therapy ; Colon/drug effects/immunology/microbiology/pathology ; Dextran Sulfate/administration &amp; dosage/toxicity ; Disease Models, Animal ; Extracellular Vesicles/immunology/*transplantation ; Feces ; Gastrointestinal Microbiome/*immunology ; Humans ; Intestinal Mucosa/drug effects/immunology/microbiology/pathology ; Lactobacillus plantarum/*cytology/immunology ; Male ; Mice ; *Probiotics ; }, abstract = {Probiotics plays an important role in regulating gut microbiota and maintaining intestinal homeostasis. Extracellular vesicles (EVs) derived from probiotics have emerged as potential mediators of host immune response and anti-inflammatory effect. However, the anti-inflammatory effect and mechanism of probiotics derived EVs on inflammatory bowel disease (IBD) remains unclear. In this study, the effect of Lactobacillus plantarum Q7-derived extracellular vesicles (Q7-EVs) on gut microbiota and intestinal inflammation was investigated in C57BL/6J mice. The results showed that Q7-EVs alleviated DSS-induced colitis symptoms, including colon shortening, bleeding, and body weight loss. Consumption of Q7-EVs reduced the degree of histological damage. DSS-upregulated proinflammatory cytokine levels including IL-6, IL-1β, IL-2 and TNF-α were reduced significantly by Q7-EVs (p < 0.05). 16S rRNA sequencing results showed that Q7-EVs improved the dysregulation of gut microbiota and promoted the diversity of gut microbiota. It was observed that the pro-inflammatory bacteria (Proteobacteria) were reduced and the anti-inflammatory bacteria (Bifidobacteria and Muribaculaceae) were increased. These findings indicated that Q7-EVs might alleviate DSS-induced ulcerative colitis by regulating the gut microbiota.}, }
@article {pmid34923901, year = {2021}, author = {Guo, Q and Lin, H and Chen, P and Tan, S and Wen, Z and Lin, L and He, J and Wen, J and Lu, S}, title = {Dynamic changes of intestinal flora in patients with irritable bowel syndrome combined with anxiety and depression after oral administration of enterobacteria capsules.}, journal = {Bioengineered}, volume = {12}, number = {2}, pages = {11885-11897}, pmid = {34923901}, issn = {2165-5987}, mesh = {Administration, Oral ; Adult ; Aged ; Anxiety/*complications ; Bacteria/growth &amp; development ; Biodiversity ; Capsules ; Depression/*complications ; Diarrhea/complications/microbiology/therapy ; Enterobacteriaceae/*physiology ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*microbiology/*psychology/therapy ; Male ; Middle Aged ; Principal Component Analysis ; }, abstract = {This study investigated the clinical characteristics and dynamic changes of intestinal bacterial community to evaluate the curative effect of fecal microbiota transplantation (FMT) on irritable bowel syndrome with predominant diarrhea (IBS-D) comorbid with anxiety and depression. Total two treatments were designed in randomize-controlled trial includes oral FMT capsules with 1 week (A1), 8 weeks (A2), and 12 weeks (A3), as well as oral empty capsules with 1 week (B1), 8 weeks (B2), and 12 weeks (B3) as control for comparison. The positive therapeutic effects occurred in FMT colonized patient with IBS-D comorbid psychological disorder, demonstrated at alleviated IBS-D severity (IBS-SSS score from 291.11 reduced to 144.44), altered stool type (from 6 changed to 4), reduced anxiety and depression scores (from 18.33 to 8.39 and from 22.33 to 17.78) after FMT-treated 12 weeks. The FMT therapy improved bacterial alpha diversity and the majority bacterial community predominant by Bacteroidetes and Firmicutes, and the relative abundance (RA) was higher after FMT-treated 12 weeks (50.61% and 45.52%) than control (47.62% and 38.96%). In short, FMT therapy has great potential for IBS-D patients combined with anxiety and depression by alleviated clinical symptoms and restore the intestinal micro-ecology.}, }
@article {pmid34922582, year = {2021}, author = {He, Y and Du, W and Xiao, S and Zeng, B and She, X and Liu, D and Du, H and Li, L and Li, F and Ai, Q and He, J and Song, C and Wei, H and Zhao, X and Yu, J}, title = {Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {510}, pmid = {34922582}, issn = {1479-5876}, support = {82001602//National Natural Science Foundation of China/ ; 81971431//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Butyrates ; *Enterocolitis, Necrotizing/microbiology ; Humans ; Infant, Newborn ; Mice ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; T-Lymphocytes, Regulatory ; }, abstract = {BACKGROUND: Necrotizing enterocolitis (NEC) remains a life-threatening disease in neonates. Numerous studies have shown a correlation between the intestinal microbiota and NEC, but the causal link remains unclear. This study aimed to demonstrate the causal role of gut microbiota in NEC and explore potential mechanisms involved.<br><br>METHODS: Eighty-one fecal samples from patients with NEC and eighty-one matched controls (matched to the NEC infants by gestational age, birth weight, date of birth, mode of delivery and feeding patterns) were collected. To explore if altered gut microbiota contributes to the pathogenesis of NEC, fecal microbiota transplantation (FMT) was carried out in germ-free (GF) mice prior to a NEC-induction protocol that included exposure to hypoxia and cold stress. Butyric acid was also administered to demonstrate its role in NEC. The fecal microbiota from patients and mice were analyzed by 16S rRNA gene sequencing analysis. Short chain fatty acid (SCFA) levels were measured by gas chromatography-mass spectrometry (GC-MS). The ontogeny of T cells and regulatory T cells (Tregs) in lamina propria mononuclear cells (LPMC) from the ileum of patients and mice were isolated and analyzed by flow cytometry.The transcription of inflammatory cytokines was quantified by qRT-PCR.<br><br>RESULTS: NEC patients had increased Proteobacteria and decreased Firmicutes and Bacteroidetes compared to fecal control samples, and the level of butyric acid in the NEC group was lower than the control group. FMT in GF mice with samples from NEC patients achieved a higher histological injury scores when compared to mice that received FMT with control samples. Alterations in microbiota and butyrate levels were maintained in mice following FMT. The ratio of Treg/CD4[+]T (Thelper) cells was reduced in both NEC patients and mice modeling NEC following FMT.<br><br>CONCLUSIONS: The microbiota was found to have NEC and the microbial butyrate-Treg axis was identified as a potential mechanism for the observed effects.}, }
@article {pmid34920070, year = {2022}, author = {Zhang, L and Wang, Y and Wu, F and Wang, X and Feng, Y and Wang, Y}, title = {MDG, an Ophiopogon japonicus polysaccharide, inhibits non-alcoholic fatty liver disease by regulating the abundance of Akkermansia muciniphila.}, journal = {International journal of biological macromolecules}, volume = {196}, number = {}, pages = {23-34}, doi = {10.1016/j.ijbiomac.2021.12.036}, pmid = {34920070}, issn = {1879-0003}, mesh = {Akkermansia/drug effects ; Animals ; Diet, High-Fat ; Disease Models, Animal ; Drugs, Chinese Herbal ; Gastrointestinal Microbiome/*drug effects ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism/pathology ; Male ; Metagenome ; Metagenomics/methods ; Mice ; Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/metabolism ; Ophiopogon/*chemistry ; Polysaccharides/chemistry/*pharmacology ; }, abstract = {MDG, a polysaccharide derived from Ophiopogon japonicus, displays a protective effect against obesity and non-alcoholic fatty liver disease (NAFLD). However, there is no definitive evidence proving the specific mechanism of MDG against NAFLD. The results showed MDG supplementation ameliorated lipid accumulation, liver steatosis, and chronic inflammation in high-fat diet-induced NAFLD mice. Besides, MDG increased the abundance and diversity of microbial communities in the gut. These effects were mediated by the colonization of fecal microbiota. Further investigation revealed that Akkermansia muciniphila levels correlated negatively with NAFLD development, and lipid metabolism-related signaling might be the key regulator. Our study suggested that MDG treatment could inhibit obesity and the NAFLD process by modulating lipid-related pathways via altering the structure and diversity of gut microbiota. In addition, Akkermansia miniciphila might be a promising candidate in future research into NAFLD.}, }
@article {pmid34918995, year = {2021}, author = {Qi, L and Huang, X and He, C and Ji, D and Li, F}, title = {Steroid-resistant intestinal aGVHD and refractory CMV and EBV infections complicated by haplo-HSCT were successfully rescued by FMT and CTL infusion.}, journal = {The Journal of international medical research}, volume = {49}, number = {12}, pages = {3000605211063292}, pmid = {34918995}, issn = {1473-2300}, mesh = {Adult ; Cytomegalovirus ; *Epstein-Barr Virus Infections/complications/therapy ; Fecal Microbiota Transplantation ; *Graft vs Host Disease/drug therapy ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Herpesvirus 4, Human ; Humans ; Steroids/therapeutic use ; }, abstract = {Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) produces similar survival outcomes as HLA-matched sibling donor allogeneic HCST in younger patients with acquired severe aplastic anemia (SAA). This study reported a 29-years-old man with SAA and intracranial hemorrhage who underwent haplo-HSCT with a modified BU/CY + ATG conditioning regimen. Neutrophil and platelet engraftment were both achieved on day 14 after HSCT. The patient developed grade IV acute graft-versus-host disease (aGVHD) on day 20 and acquired cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections on day 47. After the failure of methylprednisolone, basiliximab, ruxolitinib, and antiviral treatment, the patient was diagnosed with steroid-resistant grade IV aGVHD and refractory CMV and EBV infections. We performed fecal microbiota transplantation and infused CMV- and EBV-specific cytotoxic T lymphocytes. After that the stool volume and frequency gradually decreased, and viral DNA was undetectable on day 80. This report provides helpful clinical experience for treating steroid-resistant aGVHD and refractory viral infections.}, }
@article {pmid34918486, year = {2022}, author = {Wang, Y and Xie, Z}, title = {Exploring the role of gut microbiome in male reproduction.}, journal = {Andrology}, volume = {10}, number = {3}, pages = {441-450}, doi = {10.1111/andr.13143}, pmid = {34918486}, issn = {2047-2927}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Male ; Prebiotics ; *Probiotics ; RNA, Ribosomal, 16S ; Reproduction ; }, abstract = {BACKGROUND: The impact of the gut microbiome on the organism has become a growing research focus with the development of 16S rRNA sequencing. However, the effect of the gut microbiome in male reproduction has yet to be investigated.<br><br>OBJECTIVE: To overview on possible mechanisms by which the gut microbiome could affect male reproduction and therapeutic opportunities related to the gut microbiome METHODS: Authors searched PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library for medical subject headings terms and free text words referred to "male infertility" "testis" "gut microbiome" "insulin resistance" "erectile dysfunction" "therapy" "sex hormones" and "genital diseases" until December 2, 2021.<br><br>RESULTS: Evidence suggests that immune system activation caused by the gut microbiome translocation not only leads to testicular and epididymal inflammation but can also induce insulin resistance together with gastrointestinal hormones such as leptin and ghrelin, which in turn affects the secretion of various sex hormones such as LH, FSH, and T to regulate spermatogenesis. In addition, the gut microbiome can influence spermatogenesis by controlling and metabolizing androgens as well as affecting the blood-testis barrier. It also promotes vascular inflammation by raising trimethylamine-N-oxide (TMAO) levels in the blood, which causes erectile dysfunction. The testicular microbiome and gut microbiome can interact to influence male reproductive function. This study discusses therapeutic options such as probiotics, prebiotics, and fecal microbiota transplantation, as well as the challenges and opportunities behind ongoing research, and emphasizes the need for additional research in the future to demonstrate the links and underlying mechanisms between the gut microbiome and male reproduction. Therapeutic options such as probiotics, prebiotics, and fecal microbiota transplantation are potential treatments for male infertility.<br><br>DISCUSSION AND CONCLUSION: Gut microbiota may have a causal role in male reproduction health, therapeutic strategies such as supplementation with appropriate probiotics could be undertaken as a complementary treatment. In the future, additional research is needed to demonstrate the links and underlying mechanisms between the gut microbiome and male reproduction.}, }
@article {pmid34918052, year = {2022}, author = {Casado-Bedmar, M and Viennois, E}, title = {MicroRNA and Gut Microbiota: Tiny but Mighty-Novel Insights into Their Cross-talk in Inflammatory Bowel Disease Pathogenesis and Therapeutics.}, journal = {Journal of Crohn's &amp; colitis}, volume = {16}, number = {6}, pages = {992-1005}, pmid = {34918052}, issn = {1876-4479}, support = {ANR-11-IDEX-0005-02//INFLAMEX/ ; //European Research Executive Agency/ ; }, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Diseases ; *Gastrointestinal Microbiome/physiology ; Humans ; *Inflammatory Bowel Diseases/diagnosis ; *MicroRNAs/genetics ; *Probiotics/therapeutic use ; }, abstract = {MicroRNAs [miRNAs], small non-coding RNAs, have recently been described as crucial contributors to intestinal homeostasis. They can interact with the gut microbiota in a reciprocal manner and deeply affect host health status, leading to several disorders when unbalanced. Inflammatory bowel disease [IBD] is a chronic inflammation of the gastrointestinal tract that co-occurs with alterations of the gut microbiota, and whose aetiology remains largely unclear. On one hand, host miRNA could be playing a relevant role in IBD pathophysiology by shaping the gut microbiota. The gut microbiome, on the other hand, may regulate the expression of host miRNAs, resulting in intestinal epithelial dysfunction, altered autophagy, and immune hyperactivation. Interestingly, it has been hypothesised that their reciprocal impact may be used for therapeutic goals. This review describes the latest research and suggests mechanisms through which miRNA and intestinal microbiota, as joint actors, may participate specifically in IBD pathophysiology. Furthermore, we discuss the diagnostic power and therapeutic potential resulting from their bidirectional communication after faecal transplantation, probiotics intake, or anti-miRNAs or miRNA mimics administration. The current literature is summarised in the present work in a comprehensive manner, hoping to provide a better understanding of the miRNA-microbiota cross-talk and to facilitate their application in IBD.}, }
@article {pmid34917313, year = {2021}, author = {Geldof, J and LeBlanc, JF and Lucaciu, L and Segal, J and Lees, CW and Hart, A}, title = {Are we addressing the top 10 research priorities in IBD?.}, journal = {Frontline gastroenterology}, volume = {12}, number = {7}, pages = {564-569}, pmid = {34917313}, issn = {2041-4137}, abstract = {BACKGROUND: Since publication of the top 10 research priorities in inflammatory bowel disease (IBD) based on the James Lind Alliance Priority Setting Partnership, the question remains whether this has influenced the IBD-research landscape. This study aimed to create an overview of the current distribution of research interests of trials in the UK.<br><br>METHODS: The ClinicalTrials.gov database and European Union Clinical Trials Register were screened for clinical trials set up from 9 August 2016 to 16 November 2019 in the UK involving adult patients with IBD.<br><br>RESULTS: Of 20 non-industry-sponsored studies, a quarter investigated treatment strategies considering efficacy, safety and cost-effectiveness (priority 1). Four evaluated the role of diet (priorities 3 and 7). Development/assessment of biomarkers for patient stratification (priority 2) and fatigue (priority 8) were subject of three studies. IBD-related pain and control of diarrhoea/incontinence were each subject of 2 studies (priorities 4 and 6). The effect of gut microbiota (priority 10) and optimal strategy for perianal Crohn's disease (priority 5) was the focus of 2 studies each. One study evaluated surgery for terminal ileal Crohn's disease (priority 9). Of 63 industry-sponsored studies, 59 focused on priority 1.<br><br>CONCLUSIONS: This study presents an impression of the breadth of the IBD-research landscape in the UK, in light of the top 10 research priorities published in 2016. Optimal treatment strategy has been the most studied research priority by academic and industry-sponsored trials. Fewer studies focused on patient-reported outcomes. It remains debatable to what extent the current research landscape adequately represents all stakeholders' viewpoints on needs for expanded knowledge in IBD, particularly the patients' perspective.}, }
@article {pmid34915267, year = {2021}, author = {Ma, X and Xu, T and Qian, M and Zhang, Y and Yang, Z and Han, X}, title = {Faecal microbiota transplantation alleviates early-life antibiotic-induced gut microbiota dysbiosis and mucosa injuries in a neonatal piglet model.}, journal = {Microbiological research}, volume = {255}, number = {}, pages = {126942}, doi = {10.1016/j.micres.2021.126942}, pmid = {34915267}, issn = {1618-0623}, abstract = {Faecal microbiota transplantation (FMT) is a promising approach to modulate the gut microbiota. Gut microbiota dysbiosis caused by antibiotic administration is a universal problem. This study aimed to evaluate the effect of FMT on the dysbiosis of gut microbiota and metabolic profiles and injury of the intestinal barrier induced by antibiotics and used a neonatal piglet model. Neonatal piglets were administered ampicillin for 3 days, and antibiotic-induced dysbiosis was evaluated by the occurrence of diarrhoea and alteration of gut microbiota. Then, FMT was conducted for 3 days to rebuild the gut microbiota. High-throughput sequencing and a mass spectrometry platform were used for integrated microbiome-metabolome analysis. The results showed that antibiotics led to a decline in the diversity of gut microbiota. Furthermore, there was an increase in the relative abundance of potential pathogenic bacteria, such as Oscillibacter, Pseudomonas and Eubacterium, and an increase in the relative abundance of tetracycline resistance genes (tet genes). FMT restored the diversity and promoted the relative abundance of beneficial bacteria, such as Parabacteroides, Dorea and Parasutterella, while decreasing the relative abundance of tet genes. Untargeted metabolomics analysis found that alpha linolenic acid and linoleic acid metabolism were the key metabolic pathways utilized in the FMT group, and targeted metabolomics analysis further verified the variation in the associated metabolites arachidonic acid and conjugated linoleic acid. FMT also significantly enhanced the relative expression of tight junction (ZO-1, claudin-1 and occludin) and adherens junction (β-catenin, E-cadherin) proteins and anti-inflammatory cytokines (IL-10, TGF-β1) and reduced the production of proinflammatory cytokines (IL-6, IL-1β, TNF-α and IFN-γ) in the colon. FMT not only modulated the gut microbiota composition and microbial metabolism but also reduced the relative abundance of tet genes, improving the intestinal barrier function and inflammatory responses in antibiotic-treated piglets.}, }
@article {pmid34912583, year = {2021}, author = {Hollingshead, C and Ciricillo, J and Kammeyer, J}, title = {Ethical Implications of the Fecal Microbiota Transplantation: Disclosure of a False-Positive HIV Test.}, journal = {Case reports in infectious diseases}, volume = {2021}, number = {}, pages = {6696542}, pmid = {34912583}, issn = {2090-6625}, abstract = {Fecal microbiota transplantation (FMT) has gained popularity as an effective therapeutic option for Clostridioides difficile infection (CDI). Since its FDA recognition as a treatment modality for recurrent CDI in 2013, screening protocols for FMT donor stool have been in flux. However, extensive health questionnaires, in combination with serological and stool assays, have become mainstays in the donor screening process, although ethical implications are yet to be thoroughly considered. Herein, we present the case of a family member found to have a false-positive HIV test during the donor screening process and discuss potential ethical ramifications associated with FMT stool donation.}, }
@article {pmid34912328, year = {2021}, author = {Liang, M and Liwen, Z and Jianguo, S and Juan, D and Fei, D and Yin, Z and Changping, W and Jianping, C}, title = {Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {728723}, pmid = {34912328}, issn = {1664-3224}, mesh = {Adult ; Aged ; Animals ; Autoantibodies/immunology ; Autoantigens/immunology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Hepatitis, Autoimmune/*immunology/*microbiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; T Follicular Helper Cells/*immunology ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Intestinal microbiota (IM) dysbiosis contributes to the development of autoimmune hepatitis (AIH). This study aimed to investigate the potential effect of fecal microbiota transplantation (FMT) in a murine model of experimental AIH (EAH), a condition more similar to that of AIH patients. Changes in the enteric microbiome were determined in AIH patients and EAH mice. Moreover, we established an experimental model of secondary EAH mice harboring dysbiosis (ABx) to analyze the effects of therapeutic FMT administration on follicular regulatory T (TFR) and helper T (TFH) cell imbalances and IM composition in vivo. Alterations of the IM composition and bacterial translocation occurred in AIH patients compared to nonalcoholic fatty liver disease patients and healthy controls (HCs). Therapeutic FMT significantly attenuated liver injury and bacterial translocation and improved the imbalance between splenic TFR cells and TFH cells in ABx EAH mice. Furthermore, therapeutic FMT also partially reversed the increasing trend in serum liver enzymes (ALT and AST) of CXCR5-/-EAH mice on the 28th day. Finally, therapeutic FMT could effectively restore antibiotic-induced IM dysbiosis in EAH mice. Taken together, our findings demonstrated that FMT was capable of controlling hepatitis progression in EAH mice, and the associated mechanism might be involved in the regulation of the TFR/TFH immune imbalance and the restoration of IM composition.}, }
@article {pmid34907387, year = {2021}, author = {O'Leary, K}, title = {FMT for patients with cancer.}, journal = {Nature medicine}, volume = {27}, number = {12}, pages = {2057}, doi = {10.1038/s41591-021-01611-3}, pmid = {34907387}, issn = {1546-170X}, mesh = {*Fecal Microbiota Transplantation ; Humans ; Melanoma/*therapy ; Treatment Outcome ; }, }
@article {pmid34906228, year = {2021}, author = {Shin, J and Noh, JR and Choe, D and Lee, N and Song, Y and Cho, S and Kang, EJ and Go, MJ and Ha, SK and Chang, DH and Kim, JH and Kim, YH and Kim, KS and Jung, H and Kim, MH and Sung, BH and Lee, SG and Lee, DH and Kim, BC and Lee, CH and Cho, BK}, title = {Ageing and rejuvenation models reveal changes in key microbial communities associated with healthy ageing.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {240}, pmid = {34906228}, issn = {2049-2618}, mesh = {Aging ; Animals ; *Gastrointestinal Microbiome/genetics ; *Healthy Aging ; Mice ; *Microbiota ; Rejuvenation ; }, abstract = {BACKGROUND: The gut microbiota is associated with diverse age-related disorders. Several rejuvenation methods, such as probiotic administration and faecal microbiota transplantation, have been applied to alter the gut microbiome and promote healthy ageing. Nevertheless, prolongation of the health span of aged mice by remodelling the gut microbiome remains challenging.<br><br>RESULTS: Here, we report the changes in gut microbial communities and their functions in mouse models during ageing and three rejuvenation procedures including co-housing, serum-injection and parabiosis. Our results showed that the compositional structure and gene abundance of the intestinal microbiota changed dynamically during the ageing process. Through the three rejuvenation procedures, we observed that the microbial community and intestinal immunity of aged mice were comparable to those of young mice. The results of metagenomic data analysis underscore the importance of the high abundance of Akkermansia and the butyrate biosynthesis pathway in the rejuvenated mouse group. Furthermore, oral administration of Akkermansia sufficiently ameliorated the senescence-related phenotype in the intestinal systems in aged mice and extended the health span, as evidenced by the frailty index and restoration of muscle atrophy.<br><br>CONCLUSIONS: In conclusion, the changes in key microbial communities and their functions during ageing and three rejuvenation procedures, and the increase in the healthy lifespan of aged mice by oral administration of Akkermansia. Our results provide a rationale for developing therapeutic strategies to achieve healthy active ageing. Video abstract.}, }
@article {pmid34904826, year = {2021}, author = {Zhao, Y and Chen, X and Shen, J and Xu, A and Wang, Y and Meng, Q and Xu, P}, title = {Black Tea Alleviates Particulate Matter-Induced Lung Injury via the Gut-Lung Axis in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {50}, pages = {15362-15373}, doi = {10.1021/acs.jafc.1c06796}, pmid = {34904826}, issn = {1520-5118}, mesh = {Animals ; *Camellia sinensis ; Lung ; *Lung Injury/etiology/prevention &amp; control ; Mice ; Mice, Inbred C57BL ; Particulate Matter/toxicity ; Tea ; }, abstract = {Black tea, as the most consumed kind of tea, is shown to have beneficial effects on human health. However, its impact on particulate matter (PM) induced lung injury and the mechanisms involved have been sparsely addressed. Here, we show that PM-exposed mice exhibited oxidative stress and inflammation in the lungs, which was significantly alleviated by a daily intake of black tea infusion (TI) in a concentration-dependent manner. Interestingly, both the ethanol-soluble fraction (ES) and the ethanol precipitate fraction (EP) exhibited better effects than those of TI; moreover, EP tended to have stronger protection than ES in some indicators, implying that EP played a dominant role in the prevention effects. Furthermore, fecal microbiota transplantation (FMT) revealed that the gut microbiota was differentially reshaped by TI and its fractions were able to directly alleviate the injury induced by PMs. These results indicate that daily intake of black tea and its fractions, especially EP, may alleviate particulate matter-induced lung injury via the gut-lung axis in mice. In addition, the Lachnospiraceae_NK4A136_group could be the core gut microbe contributing to the protection of EP and thus should be further studied in the future.}, }
@article {pmid34903050, year = {2021}, author = {Beller, L and Deboutte, W and Falony, G and Vieira-Silva, S and Tito, RY and Valles-Colomer, M and Rymenans, L and Jansen, D and Van Espen, L and Papadaki, MI and Shi, C and Yinda, CK and Zeller, M and Faust, K and Van Ranst, M and Raes, J and Matthijnssens, J}, title = {Successional Stages in Infant Gut Microbiota Maturation.}, journal = {mBio}, volume = {12}, number = {6}, pages = {e0185721}, pmid = {34903050}, issn = {2150-7511}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Cohort Studies ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Infant ; Infant, Newborn/*growth &amp; development ; Male ; }, abstract = {Disturbances in the primary colonization of the infant gut can result in lifelong consequences and have been associated with a range of host conditions. Although early-life factors have been shown to affect infant gut microbiota development, our current understanding of human gut colonization in early life remains limited. To gain more insights into the unique dynamics of this rapidly evolving ecosystem, we investigated the microbiota over the first year of life in eight densely sampled infants (n = 303 total samples). To evaluate the gut microbiota maturation transition toward an adult configuration, we compared the microbiome composition of the infants to that of the Flemish Gut Flora Project (FGFP) population (n = 1,106). We observed the infant gut microbiota to mature through three distinct, conserved stages of ecosystem development. Across these successional gut microbiota maturation stages, the genus predominance was observed to shift from Escherichia over Bifidobacterium to Bacteroides. Both disease and antibiotic treatment were observed to be associated occasionally with gut microbiota maturation stage regression, a transient setback in microbiota maturation dynamics. Although the studied microbiota trajectories evolved to more adult-like constellations, microbiome community typing against the background of the FGFP cohort clustered all infant samples within the (in adults) potentially dysbiotic Bacteroides 2 (Bact2) enterotype. We confirmed the similarities between infant gut microbial colonization and adult dysbiosis. Profound knowledge about the primary gut colonization process in infants might provide crucial insights into how the secondary colonization of a dysbiotic adult gut can be redirected. IMPORTANCE After birth, microbial colonization of the infant intestinal tract is important for health later in life. However, this initial process is highly dynamic and influenced by many factors. Studying this process in detail requires a dense longitudinal sampling effort. In the current study, the bacterial microbiota of >300 stool samples was analyzed from 8 healthy infants, suggesting that the infant gut microbial population matures along a path involving distinct microbial constellations and that the timing of these transitions is infant specific and can temporarily retrace upon external events. We also showed that the infant microbial populations show similarities to suboptimal bacterial populations in the guts of adults. These insights are crucial for a better understanding of the dynamics and characteristics of a "healthy gut microbial population" in both infants and adults and might allow the identification of intervention targets in cases of microbial disturbances or disease.}, }
@article {pmid34903043, year = {2021}, author = {Hou, G and Zeng, Q and Matthijnssens, J and Greenberg, HB and Ding, S}, title = {Rotavirus NSP1 Contributes to Intestinal Viral Replication, Pathogenesis, and Transmission.}, journal = {mBio}, volume = {12}, number = {6}, pages = {e0320821}, pmid = {34903043}, issn = {2150-7511}, support = {K99 AI135031/AI/NIAID NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; R00 AI135031/AI/NIAID NIH HHS/United States ; R01 AI150796/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; Interferons/genetics/metabolism ; Intestines/metabolism/*virology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Rotavirus/genetics/*pathogenicity/*physiology ; Rotavirus Infections/genetics/metabolism/*virology ; STAT1 Transcription Factor/genetics/metabolism ; Viral Nonstructural Proteins/genetics/*metabolism ; *Virus Replication ; }, abstract = {Rotavirus (RV)-encoded nonstructural protein 1 (NSP1), the product of gene segment 5, effectively antagonizes host interferon (IFN) signaling via multiple mechanisms. Recent studies with the newly established RV reverse genetics system indicate that NSP1 is not essential for the replication of the simian RV SA11 strain in cell culture. However, the role of NSP1 in RV infection in vivo remains poorly characterized due to the limited replication of heterologous simian RVs in the suckling mouse model. Here, we used an optimized reverse genetics system and successfully recovered recombinant murine RVs with or without NSP1 expression. While the NSP1-null virus replicated comparably with the parental murine RV in IFN-deficient and IFN-competent cell lines in vitro, it was highly attenuated in 5-day-old wild-type suckling pups in both the 129sv and C57BL/6 backgrounds. In the absence of NSP1 expression, murine RV had significantly reduced replication in the ileum, systemic spread to mesenteric lymph nodes, fecal shedding, diarrhea occurrence, and transmission to uninoculated littermates. The defective replication of the NSP1-null RV in small intestinal tissues occurred as early as 1 day postinfection. Of interest, the replication and pathogenesis defects of NSP1-null RV were only minimally rescued in Stat1 knockout pups, suggesting that NSP1 facilitates RV replication in an IFN-independent manner. Our findings highlight a pivotal function of NSP1 during homologous RV infections in vivo and identify NSP1 as an ideal viral protein for targeted attenuation for future vaccine development. IMPORTANCE Rotavirus remains one of the most important causes of severe diarrhea and dehydration in young children worldwide. Although NSP1 is dispensable for rotavirus replication in cell culture, its exact role in virus infection in vivo remains unclear. In this study, we demonstrate, for the first time in a pathologically valid homologous small animal model, that in the context of a fully replication-competent, pathogenic, and transmissible murine rotavirus, loss of NSP1 expression substantially attenuated virus replication in the gastrointestinal tract, diarrheal disease, and virus transmission. Notably, the NSP1-deficient murine rotavirus also replicated poorly in mice lacking host interferon or inflammasome signaling. Our data provide the first piece of evidence that NSP1 is essential for murine rotavirus replication in vivo, making it an attractive target for developing improved next-generation rotavirus vaccines better suited for socioeconomically disadvantaged and immunocompromised individuals.}, }
@article {pmid34902790, year = {2021}, author = {Yao, D and Dai, W and Dong, M and Dai, C and Wu, S}, title = {MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis.}, journal = {EBioMedicine}, volume = {74}, number = {}, pages = {103751}, pmid = {34902790}, issn = {2352-3964}, mesh = {Anti-Bacterial Agents/therapeutic use ; Colitis, Ulcerative/*metabolism/microbiology/pathology/therapy ; Combined Modality Therapy ; Dietary Supplements ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/pathology ; Mucin-2/*metabolism ; }, abstract = {The mucin2 (MUC2) mucus barrier acts as the first barrier that prevents direct contact between intestinal bacteria and colonic epithelial cells. Bacterial factors related to the MUC2 mucus barrier play important roles in the response to changes in dietary patterns, MUC2 mucus barrier dysfunction, contact stimulation with colonic epithelial cells, and mucosal and submucosal inflammation during the occurrence and development of ulcerative colitis (UC). In this review, these underlying mechanisms are summarized and updated, and related interventions for treating UC, such as dietary adjustment, exogenous repair of the mucus barrier, microbiota transplantation and targeted elimination of pathogenic bacteria, are suggested. Such interventions are likely to induce and maintain a long and stable remission period and reduce or even avoid the recurrence of UC. A better mechanistic understanding of the MUC2 mucus barrier and its related bacterial factors may help researchers and clinicians to develop novel approaches for treating UC.}, }
@article {pmid34901192, year = {2021}, author = {Adamczak, M and Surma, S}, title = {Metabolic Acidosis in Patients with CKD: Epidemiology, Pathogenesis, and Treatment.}, journal = {Kidney diseases (Basel, Switzerland)}, volume = {7}, number = {6}, pages = {452-467}, pmid = {34901192}, issn = {2296-9381}, abstract = {BACKGROUND: Metabolic acidosis in CKD is diagnosed in patients with plasma or venous blood bicarbonate concentration lower than 22 mmol/L. Metabolic acidosis occurs in about 20% of patients with CKD. Metabolic acidosis may lead to dysfunction of many systems and organs as well as CKD progression. Currently, sodium bicarbonate is mainly used for pharmacological treatment of metabolic acidosis in patients with CKD. Veverimer is a new drug dedicated to treatment of metabolic acidosis in patients with CKD. Orally given veverimer binds hydrogen ions in the intestines and subsequently is excreted from the body with feces. Clinical studies have shown that veverimer is effective in increasing serum bicarbonate concentrations in CKD patients with metabolic acidosis. Here, we present review of the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients.<br><br>SUMMARY: Metabolic acidosis is common in patients with CKD and contributes to CKD progression and many complications, which worsen the prognosis in these patients. Currently, sodium bicarbonate is mainly used in metabolic acidosis treatment. The role of the new drug veverimer in the metabolic acidosis therapy needs further studies.<br><br>KEY MESSAGE: The aim of this review article is to summarize the current knowledge concerning the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients.}, }
@article {pmid34900994, year = {2021}, author = {Rocco, A and Sgamato, C and Compare, D and Coccoli, P and Nardone, OM and Nardone, G}, title = {Gut Microbes and Hepatic Encephalopathy: From the Old Concepts to New Perspectives.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {748253}, pmid = {34900994}, issn = {2296-634X}, abstract = {Hepatic encephalopathy (HE) is a severe complication of advanced liver disease and acute liver failure. The clinical spectrum ranges from minor cognitive dysfunctions to lethargy, depressed consciousness, and coma and significantly impact the quality of life, morbidity, and mortality of the patients. It is commonly accepted that the gut milieu is essential for the development of HE; however, despite intensive research efforts, the pathogenesis of HE is still not fully elucidated. As our knowledge of gut microbiota moves from the pioneering era of culture-dependent studies, the connection between microbes, inflammation, and metabolic pathways in the pathogenesis of HE is becoming increasingly clear, providing exciting therapeutic perspectives. This review will critically examine the latest research findings on the role of gut microbes in the pathophysiological pathways underlying HE. Moreover, currently available therapeutic options and novel treatment strategies are discussed.}, }
@article {pmid34900069, year = {2021}, author = {Shi, CY and Yu, CH and Yu, WY and Ying, HZ}, title = {Gut-Lung Microbiota in Chronic Pulmonary Diseases: Evolution, Pathogenesis, and Therapeutics.}, journal = {The Canadian journal of infectious diseases &amp; medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale}, volume = {2021}, number = {}, pages = {9278441}, pmid = {34900069}, issn = {1712-9532}, abstract = {The microbiota colonized in the human body has a symbiotic relationship with human body and forms a different microecosystem, which affects human immunity, metabolism, endocrine, and other physiological processes. The imbalance of microbiota is usually linked to the aberrant immune responses and inflammation, which eventually promotes the occurrence and development of respiratory diseases. Patients with chronic respiratory diseases, including asthma, COPD, bronchiectasis, and idiopathic pulmonary fibrosis, often have alteration of the composition and function of intestinal and lung microbiota. Gut microbiota affects respiratory immunity and barrier function through the lung-gut microbiota, resulting in altered prognosis of chronic respiratory diseases. In turn, lung dysbiosis promotes aggravation of lung diseases and causes intestinal dysfunction through persistent activation of lymphoid cells in the body. Recent advances in next-generation sequencing technology have disclosed the pivotal roles of lung-gut microbiota in the pathogenesis of chronic respiratory diseases. This review focuses on the association between the gut-lung dysbiosis and respiratory diseases pathogenesis. In addition, potential therapeutic modalities, such as probiotics and fecal microbiota transplantation, are also evaluated for the prevention of chronic respiratory diseases.}, }
@article {pmid34899638, year = {2021}, author = {Zhang, P and Fang, J and Li, G and Zhang, L and Lai, X and Xu, L and Liu, L and Xiong, Y and Li, L and Zhang, T and Wan, J and Xu, H and Chen, R and Zhang, W and Ma, J and Chen, Z}, title = {Sex Differences in Fecal Microbiota Correlation With Physiological and Biochemical Indices Associated With End-Stage Renal Disease Caused by Immunoglobulin a Nephropathy or Diabetes.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {752393}, pmid = {34899638}, issn = {1664-302X}, abstract = {This study investigated the sex-specific differences in the correlation between intestinal microbiota and end-stage renal disease. Here, we compared the differences in the gut microbiota of male and female healthy controls (HC) and patients with end-stage renal disease (ESRD) caused by immunoglobulin A (IgA) nephropathy (ESRD-IgAN) or type-2 diabetes mellitus (ESRD-T2DM) using high-throughput sequencing of the 16S rRNA gene. We also analyzed the correlation between gut microbiota and clinical immune indicators. We assigned 8, 10, 5, 7, 11, and 20 volunteers to female HC, ESRD-IgAN, and ESRD-T2DM, and male HC, ESRD-IgAN, and ESRD-T2DM, respectively. The results showed sex-specific differences in both physiological and biochemical indices and intestinal microbiota composition, as well as the correlation between them. The correlations between physiological and biochemical indices in men were significantly lower than those in women, especially for indices related to immunity, blood glucose, and cardiac color sonography. Urine output, lymphocyte ratio, serum albumin, blood calcium, dialysis status, serum urea nitrogen, urine protein, and diabetes significantly correlated with male fecal microbiota composition, whereas only creatinine and 2-h post-prandial blood glucose significantly correlated with female fecal microbiota composition. The top 50 dominant operational taxonomic units showed a stronger correlation with physiological and biochemical indices in samples obtained from females than from males. These differences highlight sex-specific differences in the effectiveness of ESRD prevention and treatments via regulating intestinal microbiota.}, }
@article {pmid34898421, year = {2021}, author = {Tu, T and Zhao, C}, title = {Treating autism spectrum disorder by intervening with gut microbiota.}, journal = {Journal of medical microbiology}, volume = {70}, number = {12}, pages = {}, doi = {10.1099/jmm.0.001469}, pmid = {34898421}, issn = {1473-5644}, mesh = {*Autism Spectrum Disorder/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; }, abstract = {Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders with a high prevalence in childhood. The gut microbiota can affect human cognition and moods and has a strong correlation with ASD. Microbiota transplantation, including faecal microbiota transplantation (FMT), probiotics, breastfeeding, formula feeding, gluten-free and casein-free (GFCF) diet and ketogenic diet therapy, may provide satisfying effects for ASD and its related various symptoms. For instance, FMT can improve the core symptoms of ASD and gastrointestinal symptoms. Probiotics, breastfeeding and formula feeding, and GFCF diet can improve gastrointestinal symptoms. The core symptom score still needs to be confirmed by large-scale clinical randomized controlled studies. It is recommended to use a ketogenic diet to treat patients with epilepsy in ASD. At present, the unresolved problems include which of gut the microbiota are beneficial, which of the microorganisms are harmful, how to safely and effectively implant beneficial bacteria into the human body, and how to extract and eliminate harmful microorganisms before transplantation. In future studies, large sample and randomized controlled clinical studies are needed to confirm the mechanism of intestinal microorganisms in the treatment of ASD and the method of microbial transplantation.}, }
@article {pmid34896553, year = {2022}, author = {Gotoh, K and Sakaguchi, Y and Kato, H and Osaki, H and Jodai, Y and Wakuda, M and Také, A and Hayashi, S and Morita, E and Sugie, T and Ito, Y and Ohmiya, N}, title = {Fecal microbiota transplantation as therapy for recurrent Clostridioides difficile infection is associated with amelioration of delirium and accompanied by changes in fecal microbiota and the metabolome.}, journal = {Anaerobe}, volume = {73}, number = {}, pages = {102502}, doi = {10.1016/j.anaerobe.2021.102502}, pmid = {34896553}, issn = {1095-8274}, mesh = {Aged, 80 and over ; *Clostridioides difficile ; *Clostridium Infections/drug therapy ; *Delirium ; Fecal Microbiota Transplantation ; Female ; Humans ; Metabolome ; *Microbiota ; Quality of Life ; Recurrence ; Treatment Outcome ; }, abstract = {Recurrent Clostridioides difficile infection (rCDI) is a frustrating condition that may affect a person's quality of life for months. Microbiome-based therapy such as fecal microbiota transplantation (FMT) has been effective for the treatment of rCDI by correcting the imbalance of the gut microbiota. Appropriate antibiotic treatment is recommended for at least two recurrences before offering FMT. Here, we report the case of a 92-year-old woman who experienced five recurrences of Clostridioides difficile infection (CDI) (six episodes in total) complicated by dementia and delirium, both of which were dramatically improved by FMT, which was associated with alterations in fecal microbiota and the metabolome. Analyses of whole microbial communities and metabolomic analyses were performed on stool specimens collected from the patient on the first episode, the third episode, the day of FMT (before FMT), and 2, 8, and 23 weeks after the FMT and from the donor. The patient had various fecal dysbioses on the first and third episodes and on the day of FMT. Two weeks after FMT, diversity of the gut bacteriome as well as the virome increased dramatically and was reflected in a positive clinical outcome for this patient. Metabolomic analysis revealed that short-chain fatty acids, which have been reported to be associated with improved memory function, were increased after FMT.}, }
@article {pmid34896249, year = {2022}, author = {Kang, Y and Kang, X and Yang, H and Liu, H and Yang, X and Liu, Q and Tian, H and Xue, Y and Ren, P and Kuang, X and Cai, Y and Tong, M and Li, L and Fan, W}, title = {Lactobacillus acidophilus ameliorates obesity in mice through modulation of gut microbiota dysbiosis and intestinal permeability.}, journal = {Pharmacological research}, volume = {175}, number = {}, pages = {106020}, doi = {10.1016/j.phrs.2021.106020}, pmid = {34896249}, issn = {1096-1186}, mesh = {Adipose Tissue, Brown ; Animals ; Endotoxemia/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Gene Expression ; Insulin Resistance ; Intestinal Mucosa/metabolism ; *Lactobacillus acidophilus ; Lipid Metabolism/genetics ; Male ; Mice, Inbred C57BL ; Obesity/metabolism/microbiology/*therapy ; Permeability ; Probiotics/*therapeutic use ; Mice ; }, abstract = {Obesity associated with low-grade chronic inflammation and intestinal dysbiosis is considered as a worldwide public health crisis. In the meanwhile, different probiotics have demonstrated beneficial effects on this condition, thus increasing the interest in the development of probiotic treatments. In this context, the aim of this study is to investigate the anti-obesity effects of potential probiotic Lactobacillus acidophilus isolated from the porcine gut. Then, it is found that L. acidophilus reduces body weight, fat mass, inflammation and insulin resistance in mice fed with a high-fat diet (HFD), accompanied by activation in brown adipose tissue (BAT) as well as improvements of energy, glucose and lipid metabolism. Besides, our data indicate that L. acidophilus not only reverses HFD-induced gut dysbiosis, as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin bearing Gram-negative bacteria levels, but also maintains intestinal barrier integrity, reduces metabolic endotoxemia, and inhibits the TLR4 / NF- κB signaling pathway. In addition, the results of microbiome phenotype prediction by BugBase and bacterial functional potential prediction using PICRUSt show that L. acidophilus treatment improves the gut microbiota functions involving metabolism, immune response, and pathopoiesia. Furthermore, the anti-obesity effect is transmissible via horizontal faeces transfer from L. acidophilus-treated mice to HFD-fed mice. According to our data, it is seen that L. acidophilus could be a good candidate for probiotic of ameliorating obesity and associated diseases such as hyperlipidemia, nonalcoholic fatty liver diseases, and insulin resistance through its anti-inflammatory properties and alleviation of endothelial dysfunction and gut dysbiosis.}, }
@article {pmid34896161, year = {2022}, author = {de Souza, JB and Brelaz-de-Castro, MCA and Cavalcanti, IMF}, title = {Strategies for the treatment of colorectal cancer caused by gut microbiota.}, journal = {Life sciences}, volume = {290}, number = {}, pages = {120202}, doi = {10.1016/j.lfs.2021.120202}, pmid = {34896161}, issn = {1879-0631}, mesh = {Colorectal Neoplasms/*microbiology/prevention &amp; control/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Microbiota ; Probiotics/therapeutic use ; }, abstract = {Colorectal cancer (CRC), also named as colon and rectal or bowel cancer, is one of the leading neoplasia diagnosed in the world. Genetic sequencing studies of microorganisms from the intestinal microbiota of patients with CRC revealed that changes in its composition occur with the development of the disease, which can play a fundamental role in its development, being mediated by the production of metabolites and toxins that damage enterocytes. Some microorganisms are frequently reported in the literature as the main agents of this process, such as the bacteria Fusobacterium nucleatum, Escherichia coli and Bacteroides fragilis. Thus, understanding the mechanisms and function of each microorganism in CRC is essential for the development of treatment tools that focus on the gut microbiota. This review verifies current research aimed at evaluating the microorganisms present in the microbiota that can influence the development of CRC, as well as possible forms of treatment that can prevent the initiation and/or spread of this disease. Due to the incidence of CRC, alternatives have been launched considering factors beyond those already known in the disease development, such as diet, fecal microbiota transplantation, use of probiotics and antibiotics, which have been widely studied for this purpose. However, despite being promising, the studies that focus on the development of new therapeutic approaches targeting the microorganisms that cause CRC still need to be improved and better developed, involving new techniques to elucidate the effectiveness and safety of these new methods.}, }
@article {pmid34893247, year = {2022}, author = {Wu, W and Zhou, J and Xuan, R and Chen, J and Han, H and Liu, J and Niu, T and Chen, H and Wang, F}, title = {Dietary κ-carrageenan facilitates gut microbiota-mediated intestinal inflammation.}, journal = {Carbohydrate polymers}, volume = {277}, number = {}, pages = {118830}, doi = {10.1016/j.carbpol.2021.118830}, pmid = {34893247}, issn = {1879-1344}, mesh = {Anti-Bacterial Agents/administration &amp; dosage/*pharmacology ; Carrageenan/administration &amp; dosage/*pharmacology ; Citrobacter rodentium/*drug effects ; Dietary Supplements ; Gastrointestinal Microbiome/*drug effects ; Inflammation/*drug therapy/metabolism/microbiology ; Intestines/*drug effects/metabolism/microbiology ; Microbial Sensitivity Tests ; }, abstract = {The inflammatory effects of carrageenan (CGN), a ubiquitous food additive, remains controversial. Gut microbiota and intestinal homeostasis may be a breakthrough in resolving this controversy. Here we show that, κ-CGN did not cause significant inflammatory symptoms, but it did cause reduced bacteria-derived short-chain fatty acids (SCFAs) and decreased thickness of the mucus layer by altering microbiota composition. Administration of the pathogenic bacterium Citrobacter rodentium, further aggravated the inflammation and mucosal damage in the presence of κ-CGN. Mucus layer degradation and altered SCFA levels could be reproduced by fecal transplantation from κ-CGN-fed mice, but not from germ-free κ-CGN-fed mice. These symptoms could be partially repaired by administering probiotics. Our results suggest that κ-CGN may not be directly inflammatory, but it creates an environment that favors inflammation by perturbation of gut microbiota composition and then facilitates expansion of pathogens, and this effect may be partially reversed by the introduction of probiotics.}, }
@article {pmid34890843, year = {2022}, author = {Di Martino, L and De Salvo, C and Buela, KA and Hager, C and Ghannoum, M and Osme, A and Buttò, L and Bamias, G and Pizarro, TT and Cominelli, F}, title = {Candida tropicalis Infection Modulates the Gut Microbiome and Confers Enhanced Susceptibility to Colitis in Mice.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {13}, number = {3}, pages = {901-923}, pmid = {34890843}, issn = {2352-345X}, support = {P01 DK091222/DK/NIDDK NIH HHS/United States ; P30 DK097948/DK/NIDDK NIH HHS/United States ; R01 DK056762/DK/NIDDK NIH HHS/United States ; R37 DK042191/DK/NIDDK NIH HHS/United States ; R01 AI145289/AI/NIAID NIH HHS/United States ; K01 DK125526/DK/NIDDK NIH HHS/United States ; R56 DK042191/DK/NIDDK NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; R56 DK055812/DK/NIDDK NIH HHS/United States ; R01 DK055812/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Candida tropicalis ; *Colitis/pathology ; Dextran Sulfate/toxicity ; *Gastrointestinal Microbiome ; Humans ; Immunity, Innate ; Lymphocytes/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND &amp; AIMS: We previously showed that abundance of Candida tropicalis is significantly greater in Crohn's disease patients compared with first-degree relatives without Crohn's disease. The aim of this study was to determine the effects and mechanisms of action of C tropicalis infection on intestinal inflammation and injury in mice.<br><br>METHODS: C57BL/6 mice were inoculated with C tropicalis, and colitis was induced by administration of dextran sodium sulfate in drinking water. Disease severity and intestinal permeability subsequently were evaluated by endoscopy, histology, quantitative reverse-transcription polymerase chain reaction, as well as 16S ribosomal RNA and NanoString analyses (NanoString Technologies, Seattle, WA).<br><br>RESULTS: Infected mice showed more severe colitis, with alterations in gut mucosal helper T cells (Th)1 and Th17 cytokine expression, and an increased frequency of mesenteric lymph node-derived group 2 innate lymphoid cells compared with uninfected controls. Gut microbiome composition, including changes in the mucin-degrading bacteria, Akkermansia muciniphila and Ruminococcus gnavus, was altered significantly, as was expression of several genes affecting intestinal epithelial homeostasis in isolated colonoids, after C tropicalis infection compared with uninfected controls. In line with these findings, fecal microbiome transplantation of germ-free recipient mice using infected vs uninfected donors showed altered expression of several tight-junction proteins and increased susceptibility to dextran sodium sulfate-induced colitis.<br><br>CONCLUSIONS: C tropicalis induces dysbiosis that involves changes in the presence of mucin-degrading bacteria, leading to altered tight junction protein expression with increased intestinal permeability and followed by induction of robust Th1/Th17 responses, which ultimately lead to an accelerated proinflammatory phenotype in experimental colitic mice.}, }
@article {pmid34889135, year = {2021}, author = {Parnell, JM and Nicholson, MR and Kellermayer, R and Kahn, SA}, title = {Pediatric Fecal Microbiota Transplantation in Recurrent Clostridioides Difficile.}, journal = {Pediatric annals}, volume = {50}, number = {12}, pages = {e515-e521}, doi = {10.3928/19382359-20211111-01}, pmid = {34889135}, issn = {1938-2359}, mesh = {Child ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {With the rising rates of Clostridioides (Clostridium) difficile infection (CDI) in children, recognizing the limitations of CDI-directed antibiotic therapy, especially in recurrent CDI (rCDI), is important. Fecal microbiota transplantation (FMT), which directly targets the underlying gut dysbiosis present in rCDI, is an important treatment option to consider in rCDI. This article will summarize indications, procedures, effectiveness, and the safety of FMT for rCDI in pediatric patients. [Pediatr Ann. 2021;50(12):e515-e521.].}, }
@article {pmid34888262, year = {2021}, author = {Li, N and Chen, H and Cheng, Y and Xu, F and Ruan, G and Ying, S and Tang, W and Chen, L and Chen, M and Lv, L and Ping, Y and Chen, D and Wei, Y}, title = {Corrigendum: Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {801376}, doi = {10.3389/fcimb.2021.801376}, pmid = {34888262}, issn = {2235-2988}, abstract = {[This corrects the article DOI: 10.3389/fcimb.2021.759435.].}, }
@article {pmid34887627, year = {2021}, author = {Barone, M and D'Amico, F and Fabbrini, M and Rampelli, S and Brigidi, P and Turroni, S}, title = {Over-feeding the gut microbiome: A scoping review on health implications and therapeutic perspectives.}, journal = {World journal of gastroenterology}, volume = {27}, number = {41}, pages = {7041-7064}, pmid = {34887627}, issn = {2219-2840}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Prebiotics ; *Synbiotics ; }, abstract = {The human gut microbiome has gained increasing attention over the past two decades. Several findings have shown that this complex and dynamic microbial ecosystem can contribute to the maintenance of host health or, when subject to imbalances, to the pathogenesis of various enteric and non-enteric diseases. This scoping review summarizes the current knowledge on how the gut microbiota and microbially-derived compounds affect host metabolism, especially in the context of obesity and related disorders. Examples of microbiome-based targeted intervention strategies that aim to restore and maintain an eubiotic layout are then discussed. Adjuvant therapeutic interventions to alleviate obesity and associated comorbidities are traditionally based on diet modulation and the supplementation of prebiotics, probiotics and synbiotics. However, these approaches have shown only moderate ability to induce sustained changes in the gut microbial ecosystem, making the development of innovative and tailored microbiome-based intervention strategies of utmost importance in clinical practice. In this regard, the administration of next-generation probiotics and engineered microbiomes has shown promising results, together with more radical intervention strategies based on the replacement of the dysbiotic ecosystem by means of fecal microbiota transplantation from healthy donors or with the introduction of synthetic communities specifically designed to achieve the desired therapeutic outcome. Finally, we provide a perspective for future translational investigations through the implementation of bioinformatics approaches, including machine and deep learning, to predict health risks and therapeutic outcomes.}, }
@article {pmid34884466, year = {2021}, author = {Yu, D and Meng, X and de Vos, WM and Wu, H and Fang, X and Maiti, AK}, title = {Implications of Gut Microbiota in Complex Human Diseases.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884466}, issn = {1422-0067}, support = {YDZJ202101ZYTS080//Jilin Province Science and Technology Department/ ; }, mesh = {Anti-Bacterial Agents/adverse effects ; Diet/*adverse effects ; Dysbiosis/etiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Humans ; Prebiotics/adverse effects ; Probiotics/adverse effects ; }, abstract = {Humans, throughout the life cycle, from birth to death, are accompanied by the presence of gut microbes. Environmental factors, lifestyle, age and other factors can affect the balance of intestinal microbiota and their impact on human health. A large amount of data show that dietary, prebiotics, antibiotics can regulate various diseases through gut microbes. In this review, we focus on the role of gut microbes in the development of metabolic, gastrointestinal, neurological, immune diseases and, cancer. We also discuss the interaction between gut microbes and the host with respect to their beneficial and harmful effects, including their metabolites, microbial enzymes, small molecules and inflammatory molecules. More specifically, we evaluate the potential ability of gut microbes to cure diseases through Fecal Microbial Transplantation (FMT), which is expected to become a new type of clinical strategy for the treatment of various diseases.}, }
@article {pmid34881818, year = {2022}, author = {Jian, YP and Yang, G and Zhang, LH and Liang, JY and Zhou, HL and Wang, YS and Xu, ZX}, title = {Lactobacillus plantarum alleviates irradiation-induced intestinal injury by activation of FXR-FGF15 signaling in intestinal epithelia.}, journal = {Journal of cellular physiology}, volume = {237}, number = {3}, pages = {1845-1856}, doi = {10.1002/jcp.30651}, pmid = {34881818}, issn = {1097-4652}, mesh = {Animals ; Bile Acids and Salts ; *Gastrointestinal Microbiome/physiology ; Intestinal Mucosa/metabolism ; Intestines ; *Lactobacillus plantarum ; Mice ; Mice, Inbred C57BL ; }, abstract = {Abdominal irradiation (IR) may destroy the intestinal mucosal barrier, leading to severe intestinal infection and multiple organ dysfunction syndromes. The role of intestinal microbiota in the development of IR-induced intestinal injury remains largely unknown. Herein, we reported that abdominal IR altered the composition of the microbiota and reduced the abundance and diversity of the gut microbiome. Alterations of bacteria, in particular reduction of Lactobacillus, played a critical role in IR-induced intestinal injury. Fecal microbiota transplant (FMT) from normal mice or administration of Lactobacillus plantarum to intestinal microbiota-eliminated mice substantially reduced IR-induced intestinal damage and prevented mice from IR-induced death. We further characterized that L. plantarum activated the farnesoid X receptor (FXR) - fibroblast growth factor 15 (FGF15) signaling in intestinal epithelial cells and hence promoted DNA-damage repair. Application of GW4064, an activator of FXR, to microbiota eliminated mice markedly mitigated IR-induced intestinal damage, reduced intestinal epithelial cell death and promoted the survival of IR mice. In contrast, suppression of FXR with Gly-β-MCA, a bile acid and an intestine-selective and high-affinity FXR inhibitor, abrogated L. Plantarum-mediated protection on the ileum of IR mice. Taken together, our findings not only provide new insights into the role of intestinal flora in radiation-induced intestinal injury but also shed new light on the application of probiotics for the protection of radiation-damaged individuals.}, }
@article {pmid34881280, year = {2021}, author = {Sun, C and Chen, L and Yang, H and Sun, H and Xie, Z and Zhao, B and Jiang, X and Qin, B and Shen, Z}, title = {Involvement of Gut Microbiota in the Development of Psoriasis Vulgaris.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {761978}, pmid = {34881280}, issn = {2296-861X}, abstract = {Objectives: Psoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis. We intend to further investigate the relationship between intestinal microbiota and psoriasis development. Design: We first performed an epidemiological investigation on differences of gastrointestinal discomfort symptoms between patients with psoriasis and general population. Then variation of gut microbiota in patients with psoriasis (un)treated with acitretin plus narrow-band ultraviolet B (NB-UVB) was analyzed by 16S rRNA sequencing. We last compared recovery status and vital cytokines (lesion and intestine) of mouse psoriasiform models, which were transplanted with fecal microbiota from patients with psoriasis or healthy controls. Results: (1) About 85.5% of patients with psoriasis vs. 58.1% of healthy controls presented with at least one gastrointestinal symptom. The prevalence of investigated symptoms (e.g., abdominal distension and constipation) were significantly higher in patients, compared with controls (p < 0.05). Passing flatus and constipation were significantly correlated with psoriasis (p < 0.05 in both cases). (2) The abundance of Ruminococcaceae family, Coprococcus_1 genus, and Blautia genus were decreased with psoriasis improvement (p < 0.05, respectively), which had been demonstrated significantly increased in psoriasis. (3) Mice receiving psoriatic microbes transplantation showed delayed recovery of psoriasiform dermatitis and less reduction of interleukin (IL)-17A than those receiving healthy microbiota or blank control (p < 0.05 and p < 0.01, respectively). Conclusion: Multiple evidence we provided here preliminarily demonstrates the involvement of gut microbiota in the different degree of psoriasis activity. The strategy based on overall microbial communities is expected to be a promising supplementary for long-term management of psoriasis.}, }
@article {pmid34880773, year = {2021}, author = {Durst, M and Graf, TR and Graf, R and Kron, M and Arras, M and Zechner, D and Palme, R and Talbot, SR and Jirkof, P}, title = {Analysis of Pain and Analgesia Protocols in Acute Cerulein-Induced Pancreatitis in Male C57BL/6 Mice.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {744638}, pmid = {34880773}, issn = {1664-042X}, abstract = {Pancreatitis is known to be painful in humans and companion animals. However, the extent of pain in experimental mouse models of acute pancreatitis is unknown. Consequently, the severity classification of acute pancreatitis in mice is controversially discussed and standardized pain management is missing. In this study, we investigated acute Cerulein-induced pancreatitis with pain-specific and well-being orientated parameters to detect its impact on mice. Male C57BL/6J male mice were injected with Cerulein; animals that received saline injections served as control group. The animals were observed for weight change and water intake. To assess pain, behaviors like stretch-and-press and reduced rearing, the Mouse Grimace Scale, and von Frey hypersensitivity were assessed. Fecal corticosterone metabolites and burrowing behavior were assessed to detect changes in the animal's well-being. Pancreatitis severity was evaluated with amylase and lipase in the blood and pancreas histology. To investigate whether different analgesics can alleviate signs of pain, and if they influence pancreas inflammation, animals received Buprenorphine, Paracetamol in combination with Tramadol, or Metamizole in the drinking water. The calculated intake of these analgesics via drinking reached values stated to be efficient for pain alleviation. While pancreatitis did not seem to be painful, we detected acute pain from Cerulein injections that could not be alleviated by analgesics. The number of inflammatory cells in the pancreas did not differ with the analgesic administered. In conclusion: (1) Cerulein injections appear to be acutely painful but pain could not be alleviated by the tested analgesics, (2) acute pancreatitis induced by our protocol did not induce obvious signs of pain, (3) analgesic substances had no detectable influence on inflammation. Nevertheless, protocols inducing more severe or even chronic pancreatitis might evoke more pain and analgesic treatment might become imperative. Considering our results, we recommend the use of Buprenorphine via drinking water in these protocols. Further studies to search for efficient analgesics that can alleviate the acute pain induced by Cerulein injections are needed.}, }
@article {pmid34880502, year = {2021}, author = {Fluhr, L and Mor, U and Kolodziejczyk, AA and Dori-Bachash, M and Leshem, A and Itav, S and Cohen, Y and Suez, J and Zmora, N and Moresi, C and Molina, S and Ayalon, N and Valdés-Mas, R and Hornstein, S and Karbi, H and Kviatcovsky, D and Livne, A and Bukimer, A and Eliyahu-Miller, S and Metz, A and Brandis, A and Mehlman, T and Kuperman, Y and Tsoory, M and Stettner, N and Harmelin, A and Shapiro, H and Elinav, E}, title = {Gut microbiota modulates weight gain in mice after discontinued smoke exposure.}, journal = {Nature}, volume = {600}, number = {7890}, pages = {713-719}, pmid = {34880502}, issn = {1476-4687}, support = {/ERC_/European Research Council/International ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cross-Sectional Studies ; Dysbiosis/etiology/metabolism/pathology ; *Gastrointestinal Microbiome ; Mice ; Models, Animal ; Smoking/metabolism/pathology ; *Smoking Cessation ; *Weight Gain ; }, abstract = {Cigarette smoking constitutes a leading global cause of morbidity and preventable death[1], and most active smokers report a desire or recent attempt to quit[2]. Smoking-cessation-induced weight gain (SCWG; 4.5 kg reported to be gained on average per 6-12 months, >10 kg year[-1] in 13% of those who stopped smoking[3]) constitutes a major obstacle to smoking abstinence[4], even under stable[5,6] or restricted[7] caloric intake. Here we use a mouse model to demonstrate that smoking and cessation induce a dysbiotic state that is driven by an intestinal influx of cigarette-smoke-related metabolites. Microbiome depletion induced by treatment with antibiotics prevents SCWG. Conversely, fecal microbiome transplantation from mice previously exposed to cigarette smoke into germ-free mice naive to smoke exposure induces excessive weight gain across diets and mouse strains. Metabolically, microbiome-induced SCWG involves a concerted host and microbiome shunting of dietary choline to dimethylglycine driving increased gut energy harvest, coupled with the depletion of a cross-regulated weight-lowering metabolite, N-acetylglycine, and possibly by the effects of other differentially abundant cigarette-smoke-related metabolites. Dimethylglycine and N-acetylglycine may also modulate weight and associated adipose-tissue immunity under non-smoking conditions. Preliminary observations in a small cross-sectional human cohort support these findings, which calls for larger human trials to establish the relevance of this mechanism in active smokers. Collectively, we uncover a microbiome-dependent orchestration of SCWG that may be exploitable to improve smoking-cessation success and to correct metabolic perturbations even in non-smoking settings.}, }
@article {pmid34880269, year = {2021}, author = {Parker-Character, J and Hager, DR and Call, TB and Pickup, ZS and Turnbull, SA and Marshman, EM and Korch, SB and Chaston, JM and Call, GB}, title = {An altered microbiome in a Parkinson's disease model Drosophila melanogaster has a negative effect on development.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {23635}, pmid = {34880269}, issn = {2045-2322}, mesh = {Animals ; Disease Models, Animal ; Drosophila Proteins/genetics ; Drosophila melanogaster/*growth &amp; development/*microbiology ; Fecal Microbiota Transplantation ; Female ; Male ; *Microbiota ; Parkinson Disease/*microbiology ; Ubiquitin-Protein Ligases/genetics ; }, abstract = {Parkinson's disease (PD) is the second most common neurodegenerative disease, besides Alzheimer's Disease, characterized by multiple symptoms, including the well-known motor dysfunctions. It is well-established that there are differences in the fecal microbiota composition between Parkinson's disease (PD) patients and control populations, but the mechanisms underlying these differences are not yet fully understood. To begin to close the gap between description and mechanism we studied the relationship between the microbiota and PD in a model organism, Drosophila melanogaster. First, fecal transfers were performed with a D. melanogaster model of PD that had a mutation in the parkin (park[25]) gene. Results indicate that the PD model feces had a negative effect on both pupation and eclosion in both control and park[25] flies, with a greater effect in PD model flies. Analysis of the microbiota composition revealed differences between the control and park[25] flies, consistent with many human studies. Conversely, gnotobiotic treatment of axenic embryos with feces-derived bacterial cultures did not affect eclosure. We speculate this result might be due to similarities in bacterial prevalence between mutant and control feces. Further, we confirmed a bacteria-potentiated impact on mutant and control fly phenotypes by measuring eclosure rate in park[25] flies that were mono-associated with members of the fly microbiota. Both the fecal transfer and the mono-association results indicate a host genotype-microbiota interaction. Overall, this study concludes functional effects of the fly microbiota on PD model flies, providing support to the developing body of knowledge regarding the influence of the microbiota on PD.}, }
@article {pmid34879222, year = {2022}, author = {Kim, E and Paik, D and Ramirez, RN and Biggs, DG and Park, Y and Kwon, HK and Choi, GB and Huh, JR}, title = {Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4[+] T cells.}, journal = {Immunity}, volume = {55}, number = {1}, pages = {145-158.e7}, pmid = {34879222}, issn = {1097-4180}, support = {R01 MH115037/MH/NIMH NIH HHS/United States ; R01 MH119459/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Autism Spectrum Disorder/*immunology/microbiology ; CD4-Positive T-Lymphocytes/*immunology ; Child ; Chromatin/*metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunization ; Inflammation/*immunology/microbiology ; Interleukin-17/*metabolism ; Intestines/*immunology ; Mice ; Neurodevelopmental Disorders/*immunology/microbiology ; Pregnancy ; Prenatal Exposure Delayed Effects/*immunology/microbiology ; }, abstract = {Children with autism spectrum disorders often display dysregulated immune responses and related gastrointestinal symptoms. However, the underlying mechanisms leading to the development of both phenotypes have not been elucidated. Here, we show that mouse offspring exhibiting autism-like phenotypes due to prenatal exposure to maternal inflammation were more susceptible to developing intestinal inflammation following challenges later in life. In contrast to its prenatal role in neurodevelopmental phenotypes, interleukin-17A (IL-17A) generated immune-primed phenotypes in offspring through changes in the maternal gut microbiota that led to postnatal alterations in the chromatin landscape of naive CD4[+] T cells. The transfer of stool samples from pregnant mice with enhanced IL-17A responses into germ-free dams produced immune-primed phenotypes in offspring. Our study provides mechanistic insights into why children exposed to heightened inflammation in the womb might have an increased risk of developing inflammatory diseases in addition to neurodevelopmental disorders.}, }
@article {pmid34877500, year = {2021}, author = {Macbeth, JC and Liu, R and Alavi, S and Hsiao, A}, title = {A dysbiotic gut microbiome suppresses antibody mediated-protection against Vibrio cholerae.}, journal = {iScience}, volume = {24}, number = {12}, pages = {103443}, pmid = {34877500}, issn = {2589-0042}, support = {R01 AI157106/AI/NIAID NIH HHS/United States ; R35 GM124724/GM/NIGMS NIH HHS/United States ; }, abstract = {Cholera is a severe diarrheal disease that places a significant burden on global health. Cholera's high morbidity demands effective prophylactic strategies, but oral cholera vaccines exhibit variable efficacy in human populations. One contributor of variance in human populations is the gut microbiome, which in cholera-endemic areas is modulated by malnutrition, cholera, and non-cholera diarrhea. We conducted fecal transplants from healthy human donors and model communities of either human gut microbes that resemble healthy individuals or those of individuals recovering from diarrhea in various mouse models. We show microbiome-specific effects on host antibody responses against Vibrio cholerae, and that dysbiotic human gut microbiomes representative of cholera-endemic areas suppress the immune response against V. cholerae via CD4+ lymphocytes. Our findings suggest that gut microbiome composition at time of infection or vaccination may be pivotal for providing robust mucosal immunity, and suggest a target for improved prophylactic and therapeutic strategies for cholera.}, }
@article {pmid34877470, year = {2021}, author = {Chauhan, U and Popov, J and Farbod, Y and Kalantar, M and Wolfe, M and Moayyedi, P and Marshall, JK and Halder, S and Kaasalainen, S}, title = {Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis: A Qualitative Assessment of Patient Perceptions and Experiences.}, journal = {Journal of the Canadian Association of Gastroenterology}, volume = {4}, number = {6}, pages = {e120-e129}, pmid = {34877470}, issn = {2515-2092}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising experimental therapy for ulcerative colitis (UC), yet patient acceptance remains poorly understood.<br><br>AIMS: The aim of this study was to explore perceptions and experiences of adult patients who received FMT for UC.<br><br>METHODS: This study used a qualitative descriptive design with thematic content analysis. Patients who were approached for enrollment in a clinical trial (NCT02606032) were invited to participate in face-to-face semistructured interviews. Two groups were interviewed: those who chose to pursue FMT and those who declined FMT. Non-FMT patients were interviewed once; FMT patients were interviewed twice at pre- and post-treatment.<br><br>RESULTS: Nine FMT patients (78% female, average age 46.7 years old) and eight non-FMT patients (50% female, average age 39.5 years old) were enrolled. Pretreatment themes included FMT as a natural therapy, external barriers to pursuing FMT, concerns with FMT and factors influencing the decision to pursue FMT. While both groups generally perceived FMT as a natural therapy, pre-FMT patients showed greater acceptance of alternative medicine. Both groups demonstrated poor understanding and similar initial concerns with product cleanliness. Pre-FMT patients were motivated to pursue FMT by feelings of last resort. Post-FMT themes included therapeutic impact of FMT and psychosocial impact of FMT. Post-FMT patients reported overall satisfaction and a unanimous preference for FMT over conventional medications.<br><br>CONCLUSION: This is the first study to assess adult patient perceptions and real-life experiences with FMT for the treatment of UC. By improving patient education, we may achieve greater acceptance of FMT.}, }
@article {pmid34876784, year = {2021}, author = {Phanchana, M and Harnvoravongchai, P and Wongkuna, S and Phetruen, T and Phothichaisri, W and Panturat, S and Pipatthana, M and Charoensutthivarakul, S and Chankhamhaengdecha, S and Janvilisri, T}, title = {Frontiers in antibiotic alternatives for Clostridioides difficile infection.}, journal = {World journal of gastroenterology}, volume = {27}, number = {42}, pages = {7210-7232}, pmid = {34876784}, issn = {2219-2840}, mesh = {Anti-Bacterial Agents/adverse effects ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/drug therapy/epidemiology ; Fecal Microbiota Transplantation ; Humans ; Vaccine Development ; }, abstract = {Clostridioides difficile (C. difficile) is a gram-positive, anaerobic spore-forming bacterium and a major cause of antibiotic-associated diarrhea. Humans are naturally resistant to C. difficile infection (CDI) owing to the protection provided by healthy gut microbiota. When the gut microbiota is disturbed, C. difficile can colonize, produce toxins, and manifest clinical symptoms, ranging from asymptomatic diarrhea and colitis to death. Despite the steady-if not rising-prevalence of CDI, it will certainly become more problematic in a world of antibiotic overuse and the post-antibiotic era. C. difficile is naturally resistant to most of the currently used antibiotics as it uses multiple resistance mechanisms. Therefore, current CDI treatment regimens are extremely limited to only a few antibiotics, which include vancomycin, fidaxomicin, and metronidazole. Therefore, one of the main challenges experienced by the scientific community is the development of alternative approaches to control and treat CDI. In this Frontier article, we collectively summarize recent advances in alternative treatment approaches for CDI. Over the past few years, several studies have reported on natural product-derived compounds, drug repurposing, high-throughput library screening, phage therapy, and fecal microbiota transplantation. We also include an update on vaccine development, pre- and pro-biotics for CDI, and toxin antidote approaches. These measures tackle CDI at every stage of disease pathology via multiple mechanisms. We also discuss the gaps and concerns in these developments. The next epidemic of CDI is not a matter of if but a matter of when. Therefore, being well-equipped with a collection of alternative therapeutics is necessary and should be prioritized.}, }
@article {pmid34873153, year = {2021}, author = {Gao, A and Su, J and Liu, R and Zhao, S and Li, W and Xu, X and Li, D and Shi, J and Gu, B and Zhang, J and Li, Q and Wang, X and Zhang, Y and Xu, Y and Lu, J and Ning, G and Hong, J and Bi, Y and Gu, W and Wang, J and Wang, W}, title = {Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {7080}, pmid = {34873153}, issn = {2041-1723}, mesh = {3T3-L1 Cells ; Androgens/*pharmacology ; Animals ; Anti-Bacterial Agents/pharmacology ; Cell Line ; Dihydrotestosterone/pharmacology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/genetics/physiology ; Glucose/*metabolism ; Glutamic Acid/blood ; Glutamine/blood ; Hep G2 Cells ; Homeostasis/*drug effects ; Humans ; Insulin Resistance/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Orchiectomy ; Sex Factors ; }, abstract = {Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes.}, }
@article {pmid34872097, year = {2022}, author = {Xie, WR and Yang, XY and Deng, ZH and Zheng, YM and Zhang, R and Wu, LH and Cai, JY and Kong, LP and Xia, HH and He, XX}, title = {Effects of Washed Microbiota Transplantation on Serum Uric Acid Levels, Symptoms, and Intestinal Barrier Function in Patients with Acute and Recurrent Gout: A Pilot Study.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {40}, number = {5}, pages = {684-690}, doi = {10.1159/000521273}, pmid = {34872097}, issn = {1421-9875}, mesh = {Endotoxins ; *Gout/complications/therapy ; Humans ; Lactic Acid ; *Microbiota ; Pilot Projects ; Uric Acid ; }, abstract = {INTRODUCTION: Gut dysbiosis has been reported to be closely associated with gout. Washed microbiota transplantation (WMT) is considered as an effective way to restore a healthy gut microbiota with less adverse events than the conventional fecal microbiota transplantation. In this study, we aimed to evaluate the effects of WMT on serum uric acid levels, symptoms, and the intestinal barrier function in patients with acute and recurrent gout.<br><br>METHODS: We performed a pilot study of WMT for acute and recurrent gout. The primary outcome was the changes in the serum uric acid level and gout symptoms. The secondary outcomes included the changes in levels of diamine oxidase (DAO), D-lactic acid, and endotoxin.<br><br>RESULTS: Eleven patients received WMT treatment. The averaged serum uric acid levels in patients with gout reduced after WMT (p = 0.031), accompanied with a decrease in the frequency and duration time of acute gout flares (p < 0.01). The levels of DAO, D-lactic acid, and endotoxin were higher in patients than in healthy donors (p < 0.05). After WMT treatment, the levels of DAO and endotoxin decreased (p < 0.05).<br><br>CONCLUSIONS: WMT is effective for reducing serum uric acid levels and improving gout symptoms in patients with gout and contributes to improve their impaired intestinal barrier function.}, }
@article {pmid34871192, year = {2022}, author = {Buckley, AM and Moura, IB and Wilcox, MH}, title = {The potential of microbiome replacement therapies for Clostridium difficile infection.}, journal = {Current opinion in gastroenterology}, volume = {38}, number = {1}, pages = {1-6}, pmid = {34871192}, issn = {1531-7056}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; }, abstract = {PURPOSE OF REVIEW: There is a paradox when treating Clostridium difficile infection (CDI); treatment antibiotics reduce C. difficile colonization but cause further microbiota disruption and can lead to recurrent disease. The success of faecal microbiota transplants (FMT) in treating CDI has become a new research area in microbiome restorative therapies but are they a viable long-term treatment option?<br><br>RECENT FINDINGS: C. difficile displays metabolic flexibility to use different nutritional sources during CDI. Using microbiome therapies for the efficient restoration of bile homeostasis and to reduce the bioavailability of preferential nutrients will target the germination ability of C. difficile spores and the growth rate of vegetative cells. Several biotechnology companies have developed microbiome therapeutics for treating CDI, which are undergoing clinical trials.<br><br>SUMMARY: There is confidence in using restorative microbiome therapies for treating CDI after the demonstrated efficacy of FMT, where several biotechnology companies are aiming to supply what would be a 'first in class' treatment option. Efficient removal of C. difficile from the different intestinal biogeographies should be considered in future microbiome therapies. With the gut microbiota implicated in different diseases, more work is needed to assess the long-term consequences of microbiome therapies.}, }
@article {pmid34870313, year = {2021}, author = {Huang, HC and Tsai, MH and Chang, CC and Pun, CK and Huang, YH and Hou, MC and Lee, FY and Hsu, SJ}, title = {Microbiota transplants from feces or gut content attenuated portal hypertension and portosystemic collaterals in cirrhotic rats.}, journal = {Clinical science (London, England : 1979)}, volume = {135}, number = {24}, pages = {2709-2728}, doi = {10.1042/CS20210602}, pmid = {34870313}, issn = {1470-8736}, mesh = {Animals ; Bile Ducts/surgery ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Hypertension, Portal/*microbiology/pathology ; Ligation ; Liver Cirrhosis/*physiopathology ; Male ; Portal Pressure ; Portasystemic Shunt, Surgical ; Rats, Sprague-Dawley ; *Splanchnic Circulation ; Rats ; }, abstract = {Liver cirrhosis and portal hypertension is the end of chronic liver injury with hepatic, splanchnic and portosystemic collateral systems dysregulation. Liver injury is accompanied by gut dysbiosis whereas dysbiosis induces liver fibrosis, splanchnic angiogenesis and dysregulated vascular tones vice versa, making portal hypertension aggravated. It has been proved that intestinal microbiota transplantation alleviates dysbiosis. Nevertheless, the influences of microbiota transplantation on cirrhosis-related portal hypertension are not so clear. Liver cirrhosis with portal hypertension was induced by bile duct ligation (BDL) in rats. Sham rats were surgical controls. Rats randomly received vehicle, fecal or gut (terminal ileum) material transplantation. The results showed that microbiota transplantation from feces or gut material significantly reduced portal pressure in cirrhotic rats (P=0.010, 0.044). Hepatic resistance, vascular contractility, fibrosis and relevant protein expressions were not significantly different among cirrhotic rats. However, microbiota transplantation ameliorated splanchnic hyperdynamic flow and vasodilatation. Mesenteric angiogenesis, defined by whole mesenteric window vascular density, decreased in both transplantation groups and phosphorylated endothelial nitric-oxide synthase (eNOS) was down-regulated. Portosystemic shunts determined by splenorenal shunt (SRS) flow decreased in both transplantation groups (P=0.037, 0.032). Shunting severity assessed by microsphere distribution method showed consistent results. Compared with sham rats, cirrhotic rats lacked Lachnospiraceae. Both microbiota transplants increased Bifidobacterium. In conclusion, microbiota transplantation in cirrhotic rats reduced portal pressure, alleviated splanchnic hyperdynamic circulation and portosystemic shunts. The main beneficial effects may be focused on portosystemic collaterals-related events, such as hepatic encephalopathy and gastroesophageal variceal hemorrhage. Further clinical investigations are mandatory.}, }
@article {pmid34867873, year = {2021}, author = {Lin, H and Guo, Q and Ran, Y and Lin, L and Chen, P and He, J and Chen, Y and Wen, J}, title = {Multiomics Study Reveals Enterococcus and Subdoligranulum Are Beneficial to Necrotizing Enterocolitis.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {752102}, pmid = {34867873}, issn = {1664-302X}, abstract = {Necrotizing enterocolitis (NEC) is a life-threatening disease for premature infants with low body weight. Due to its fragile gut microbiome and successful treatment of fecal microbiota transplantation (FMT) for intestinal disease, we aimed to reveal the multiple-omics changes after FMT and/or sulperazone treatment. In this study, 2-week-old newborn rabbits were used to simulate the NEC model and grouped into healthy control, NEC, sulperazone treatment, FTM treatment, and FMT and sulperazone combination treatment. We evaluated the intestinal pathology and survival to define the benefit from each treatment and performed microbiome and transcriptome analysis to reveal the changes in microcosmic level, which could be helpful to understand the pathogenesis of NEC and develop new strategy. We found NEC rabbits benefit more from the combination of FMT and sulperazone treatment. Combination treatment reverses a lot of microorganisms dysregulated by NEC and showed the most similar transcript profiler with healthy control. Moreover, a combination of FMT and sulperazone significantly prolonged the survival of NEC rabbits. Function enrichment showed that metabolism and viral life cycle are the most significant changes in NEC. FMT is a common therapy method for NEC. Meanwhile, in the severe situation of NEC with intestinal infection, the first therapy strategy is preferred the third-generation cephalosporin, among which sulperazone is used widely and the effect is remarkable. So, we used sulperazone to treat the rabbits with the NEC. In this research, we aim to explore the different effects on NEC between FMT and sulperazone as well as the combination. Considering the microbiome and transcriptome result, we make a conclusion that the Enterococcus and Subdoligranulum benefits NEC by influencing the bacterial phages and butyrate production, respectively.}, }
@article {pmid34867859, year = {2021}, author = {Ren, R and Gao, X and Shi, Y and Li, J and Peng, L and Sun, G and Wang, Z and Yan, B and Zhi, J and Yang, Y}, title = {Long-Term Efficacy of Low-Intensity Single Donor Fecal Microbiota Transplantation in Ulcerative Colitis and Outcome-Specific Gut Bacteria.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {742255}, pmid = {34867859}, issn = {1664-302X}, support = {F31 AA020702/AA/NIAAA NIH HHS/United States ; }, abstract = {Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria. Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT. Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group. Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.}, }
@article {pmid34867850, year = {2021}, author = {Nothaft, H and Perez-Muñoz, ME and Yang, T and Murugan, AVM and Miller, M and Kolarich, D and Plastow, GS and Walter, J and Szymanski, CM}, title = {Improving Chicken Responses to Glycoconjugate Vaccination Against Campylobacter jejuni.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {734526}, pmid = {34867850}, issn = {1664-302X}, abstract = {Campylobacter jejuni is a common cause of diarrheal disease worldwide. Human infection typically occurs through the ingestion of contaminated poultry products. We previously demonstrated that an attenuated Escherichia coli live vaccine strain expressing the C. jejuni N-glycan on its surface reduced the Campylobacter load in more than 50% of vaccinated leghorn and broiler birds to undetectable levels (responder birds), whereas the remainder of the animals was still colonized (non-responders). To understand the underlying mechanism, we conducted three vaccination and challenge studies using 135 broiler birds and found a similar responder/non-responder effect. Subsequent genome-wide association studies (GWAS), analyses of bird sex and levels of vaccine-induced IgY responses did not correlate with the responder versus non-responder phenotype. In contrast, antibodies isolated from responder birds displayed a higher Campylobacter-opsonophagocytic activity when compared to antisera from non-responder birds. No differences in the N-glycome of the sera could be detected, although minor changes in IgY glycosylation warrant further investigation. As reported before, the composition of the microbiota, particularly levels of OTU classified as Clostridium spp., Ruminococcaceae and Lachnospiraceae are associated with the response. Transplantation of the cecal microbiota of responder birds into new birds in combination with vaccination resulted in further increases in vaccine-induced antigen-specific IgY responses when compared to birds that did not receive microbiota transplants. Our work suggests that the IgY effector function and microbiota contribute to the efficacy of the E. coli live vaccine, information that could form the basis for the development of improved vaccines targeted at the elimination of C. jejuni from poultry.}, }
@article {pmid34866923, year = {2021}, author = {Chang, TT and Chen, JW}, title = {Direct CCL4 Inhibition Modulates Gut Microbiota, Reduces Circulating Trimethylamine N-Oxide, and Improves Glucose and Lipid Metabolism in High-Fat-Diet-Induced Diabetes Mellitus.}, journal = {Journal of inflammation research}, volume = {14}, number = {}, pages = {6237-6250}, pmid = {34866923}, issn = {1178-7031}, abstract = {PURPOSE: Modulation of the gut microbiota may lead to changes in pathological conditions. C-C chemokine motif ligand (CCL) 4 was upregulated in diabetes mellitus (DM) and was shown to play a significant role in pancreatic inflammation and glucose metabolism. The detailed in vivo mechanisms have not been well explored. This study aimed to investigate the hypothesis that direct CCL4 inhibition could modify gut microbiota and systemic metabolism in diet-induced DM mice.<br><br>METHODS: C57BL/6 mice fed a high-fat diet (HFD) were used as a diet-induced DM model. CCL4 inhibition was conducted by anti-CCL4 neutralizing monoclonal antibodies. The gut microbiota was analyzed by high-throughput sequencing of the 16S rRNA. Fecal microbiota transplantation (FMT) was used to verify the effect of CCL4 deficiency on gut microbiota and the linkage between CCL4-modulated gut microbiota and HFD-induced DM.<br><br>RESULTS: CCL4 inhibition stabilized glucose homeostasis, modulated lipid parameter, and decreased inflammatory markers in HFD-induced DM mice. Moreover, CCL4 inhibition reversed HFD-induced gut dysbiosis, evidenced by the decreased abundance of family Muribaculaceae and increased abundance of family Atopobiaceae when CCL4 antibodies were administrated. CCL4 inhibition led to a decrease in circulating trimethylamine N-oxide levels, a proinflammatory metabolite from gut microbiota. Taken together, CCL4 inhibition could modify gut microbiota profiles, suppress proinflammatory metabolites, reduce systemic inflammation, improve insulin resistance, and retard the progression of hyperglycemia in HFD-induced DM. Furthermore, FMT from CCL4 knockout mice rescued the glucose homeostasis in HFD-induced DM mice.<br><br>CONCLUSION: Our findings may not only provide a novel rationale to in vivo CCL4-based therapeutic approach in diet-induced DM but also indicate the significance of gut microbiota profile including the family Muribaculaceae and the family Atopobiaceae as a potential modifiable target for systemic metabolism.}, }
@article {pmid34864789, year = {2023}, author = {Tariq, R and Syed, T and Yadav, D and Prokop, LJ and Singh, S and Loftus, EV and Pardi, DS and Khanna, S}, title = {Outcomes of Fecal Microbiota Transplantation for C. difficile Infection in Inflammatory Bowel Disease : A Systematic Review and Meta-analysis.}, journal = {Journal of clinical gastroenterology}, volume = {57}, number = {3}, pages = {285-293}, doi = {10.1097/MCG.0000000000001633}, pmid = {34864789}, issn = {1539-2031}, support = {K23 DK117058/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Humans ; Child ; Fecal Microbiota Transplantation/adverse effects ; *Clostridioides difficile ; Treatment Outcome ; *Inflammatory Bowel Diseases/therapy ; *Clostridium Infections/therapy ; Recurrence ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a safe and effective therapy for recurrent Clostridioides difficile infection (CDI). Data on FMT for CDI in patients with underlying inflammatory bowel disease (IBD) are emerging but conflicting. We performed a systematic review and meta-analysis to describe the efficacy and safety of FMT for CDI in IBD and its impact on IBD outcomes.<br><br>METHODS: A systematic search of multiple databases including Embase, Scopus, and Web of Science was performed. Our primary analysis focused on pooled rate of CDI resolution after single and multiple FMTs in IBD patients. Additional analyses included rates of IBD-associated outcomes (flare, surgery, symptom improvement) after FMT. The random-effects model was used to calculate pooled rates.<br><br>RESULTS: Among 457 adult patients, 363 had CDI resolution after first FMT with a pooled cure rate of 78% [95% confidence interval (CI): 73%-83%; I2 =39%]. Overall pooled rate cure rate with single and multiple FMTs was 88% (95% CI: 81%-94%; I2 =73%). The pooled rate of an IBD flare after FMT was 26.8% (95% CI: 22.5%-31.6%; I2 =9%) and of colectomy was 7.3% (95% CI: 4.7%-10.5%; I2 =56%). Among 141 pediatric patients, 106 had CDI resolution after first FMT with pooled cure rate of 78% (95% CI: 58%-93%; I2 =59%). Overall pooled cure rate with single and multiple FMTs was 77% (95% CI: 50%-96%; I2 =63%). The pooled rate of an IBD flare after FMT was 10.8% (95% CI: 5.7%-18.5% I2 =43%), and of colectomy was 10.3% (95% CI: 2.1%-30.2% I2 =23%).<br><br>CONCLUSIONS: FMT appears to be a highly effective therapy for preventing recurrent CDI in patients with IBD. Patients who fail a single FMT may benefit from multiple FMTs.}, }
@article {pmid34864312, year = {2022}, author = {Hang, Z and Lei, T and Zeng, Z and Cai, S and Bi, W and Du, H}, title = {Composition of intestinal flora affects the risk relationship between Alzheimer's disease/Parkinson's disease and cancer.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {145}, number = {}, pages = {112343}, doi = {10.1016/j.biopha.2021.112343}, pmid = {34864312}, issn = {1950-6007}, mesh = {Alzheimer Disease/*epidemiology/microbiology ; Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Neoplasms/*epidemiology/microbiology ; Parkinson Disease/*epidemiology/microbiology ; Risk ; }, abstract = {An increasing number of epidemiological studies have shown that there is a significant inverse relationship between the onset of Alzheimer's disease/Parkinson's disease (AD/PD) and cancer, but the mechanism is still unclear. Considering that intestinal flora can connect them, we tried to explain this phenomenon from the intestinal flora. This review briefly introduced the relationship among AD/PD, cancer, and intestinal flora, studied metabolites or components of the intestinal flora and the role of intestinal barriers and intestinal hormones in AD/PD and cancer. After screening, a part of the flora capable of participating in the occurrence processes of the three diseases at the same time was obtained, the abundance changes of the special flora in AD/PD and various types of cancers were summarized, and they were classified according to the flora function and abundance, which in turn innovatively and reasonably explained the fact that AD/PD and cancer showed certain antagonism in epidemiological statistics from the perspective of intestinal flora. This review also proposed that viewing the risk relationship between diseases from the perspective of intestinal flora may provide new research ideas for the treatment of fecal microbiota transplantation (FMT) and related diseases.}, }
@article {pmid34864150, year = {2022}, author = {Trinei, M and Carpi, A and Menabo', R and Storto, M and Fornari, M and Marinelli, A and Minardi, S and Riboni, M and Casciaro, F and DiLisa, F and Petroni, K and Tonelli, C and Giorgio, M}, title = {Dietary intake of cyanidin-3-glucoside induces a long-lasting cardioprotection from ischemia/reperfusion injury by altering the microbiota.}, journal = {The Journal of nutritional biochemistry}, volume = {101}, number = {}, pages = {108921}, doi = {10.1016/j.jnutbio.2021.108921}, pmid = {34864150}, issn = {1873-4847}, mesh = {Animals ; Anthocyanins/*administration &amp; dosage ; *Cardiotonic Agents ; *Diet ; Eating ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Lymphocytes/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mitochondria, Heart/metabolism ; Myocardial Reperfusion Injury/*prevention &amp; control ; }, abstract = {The anthocyanin class of flavonoids, including cyanidin-3-glucoside (C3G) present in berries, blood oranges and pigmented cereal crops, are food bioactives with antioxidant and anti-inflammatory action, capable to reduce myocardial ischemia/reperfusion (I/R) injury by unclear mechanism. Assessing the value of sporadic beneficial diet is critical for practical application. We aimed to determine whether and how the cardioptotective effect of dietary intake of anthocyanins persists. Gene expression, histology and resistance to I/R were investigated ex vivo in hearts from mice after a month beyond the cease of the C3G-enriched diet. Cardiac injury, oxidative stress and mitochondrial damage following I/R was effectively reduced in mice fed C3G-enriched diet, even after a month of wash out with standard diet. Cardioprotection was observed also in immune-deficient mice lacking mature B and T cells indicating the anti-inflammatory activity of C3G was not involved. Moreover, the transcription reprogramming induced by the C3G-enriched diets was rescued by the wash out treatment. Instead, we found C3G-enriched diet changed the microbiome and the transplantation of the fecal microbiota transferred the cardioprotection from mice fed C3G-enriched diet to mice fed standard diet. These findings established the effect of C3G dietary intake on gut microbiota determines long lasting cardioprotection.}, }
@article {pmid34864063, year = {2022}, author = {Pradhan, S and Ray, P and Aich, P}, title = {Microbiota transplantation from younger to older mice could restore lost immunity to effectively clear salmonella infection in Th2-biased BALB/c mice.}, journal = {Life sciences}, volume = {288}, number = {}, pages = {120201}, doi = {10.1016/j.lfs.2021.120201}, pmid = {34864063}, issn = {1879-0631}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/*growth &amp; development ; Cecum/*transplantation ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Homeostasis ; Immunity, Innate ; Male ; Metabolome ; Metagenomics ; Mice ; Mice, Inbred BALB C ; Salmonella/drug effects/genetics/*immunology/metabolism ; Salmonella Infections/immunology/metabolism/microbiology/*therapy ; Th2 Cells/*immunology ; }, abstract = {AIMS: The composition, overtly abundance, and diversity of gut microbiota, play a significant role in maintaining physiological homeostasis with age. Reports revealed that the gut microbial profile might be correlated with immunity and metabolism. It is, therefore, tantamount to know if an older individual can achieve the immunity and metabolic profile of a younger individual by receiving the gut microbiome of a younger individual. In the current report, we have studied the effects of cecal microbiota transplantation (CMT) from younger to older mice.<br><br>MATERIALS AND METHODS: In this study, older BALB/c mice (23&#xa0;weeks) received CMT from younger BALB/c mice (3&#xa0;weeks).<br><br>KEY FINDINGS: CMT recipient mice showed altered expressions of immune and tight junction protein genes in the colon of mice, while the non-CMT recipient mice did not. Older mice were treated with AVNM to make them compatible with CMT. Further data from metabolite studies revealed that AVNM treatment mainly affected the aromatic amino acid biosynthesis pathway while CMT mostly affected the metabolism of different carbohydrates. We repeated the analysis in C57BL/6 mice without any significant effects of CMT.<br><br>SIGNIFICANCE: Results revealed that mice who received CMT showed more efficient restoration of gut microbiota than non-CMT recipient mice. CMT caused the alleviation of Salmonella infection and efficient recovery of the cecal index in the mice following antibiotics treatment.}, }
@article {pmid34863330, year = {2022}, author = {Haifer, C and Paramsothy, S and Kaakoush, NO and Saikal, A and Ghaly, S and Yang, T and Luu, LDW and Borody, TJ and Leong, RW}, title = {Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {2}, pages = {141-151}, doi = {10.1016/S2468-1253(21)00400-3}, pmid = {34863330}, issn = {2468-1253}, mesh = {Administration, Oral ; Adult ; Anti-Bacterial Agents/therapeutic use ; Colitis, Ulcerative/pathology/*therapy ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Female ; Freeze Drying ; Humans ; Male ; Middle Aged ; Remission Induction ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) delivered via colonoscopic infusion or enemas have been shown to induce remission in a proportion of patients with active ulcerative colitis. Whether orally administered FMT is effective in ulcerative colitis is unknown. We aimed to assess the efficacy of oral lyophilised FMT for the treatment of active ulcerative colitis.<br><br>METHODS: A double-blind, randomised, placebo-controlled trial was conducted at two centres in Australia. Eligible patients were aged 18-75 years with active ulcerative colitis (defined as clinical and endoscopic active ulcerative colitis, with a total Mayo score of 4-10, and a Mayo endoscopic subscore &#x2265;1). After 2 weeks of amoxicillin, metronidazole, and doxycycline, patients were randomly assigned in a 1:1 ratio to receive either oral lyophilised FMT or placebo capsules for 8 weeks, using a prespecified computer-generated randomisation list with a permuted block size of 8. The primary outcome was corticosteroid-free clinical remission with endoscopic remission or response (total Mayo score &#x2264;2, all subscores &#x2264;1, and &#x2265;1 point reduction in endoscopic subscore) at week 8. At week 8, FMT responders were randomly assigned (in a 1:1 ratio, permuted block size of 8) to either continue or withdraw FMT for a further 48 weeks. Analyses were done by modified intention-to-treat, including all patients who received at least one study dose. This trial is registered with Australian New Zealand Trial Registry, number ACTRN 12619000611123; this is the final report of the trial.<br><br>FINDINGS: Between May 20, 2019, and March 24, 2020, 35 patients were randomly assigned: 15 to receive FMT and 20 to receive placebo. Recruitment was terminated early due to the COVID-19 pandemic. At week 8, eight (53%) of 15 patients in the FMT group were in corticosteroid-free clinical remission with endoscopic remission or response, as were three (15%) of 20 patients in the placebo group (difference 38&#xb7;3%, 95% CI 8&#xb7;6-68&#xb7;0; p=0&#xb7;027; odds ratio 5&#xb7;0, 95% CI 1&#xb7;8-14&#xb7;1). Adverse events occurred in 10 (67%) patients in the FMT group and 17 (85%) of those in the placebo group during the 8-week induction period, and were generally mild and self-limiting gastrointestinal complaints. Serious adverse events included worsening ulcerative colitis (two in the FMT group, one in the placebo group) and per-rectal bleeding (one in the placebo group). Ten patients in the FMT group who achieved a clinical or endoscopic response entered the maintenance phase and were randomly assigned to continue open-label FMT (n=4) or withdraw therapy (n=6). All four (100%) patients who continued FMT were in clinical, endoscopic, and histologic remission at week 56 compared with none of the patients who had FMT withdrawn.<br><br>INTERPRETATION: Antibiotics followed by orally administered FMT was associated with the induction of remission in patients with active ulcerative colitis. Continuing FMT was well tolerated and appeared to demonstrate clinical, endoscopic, and histological efficacy. Oral FMT could be a promising and feasible treatment option for patients with ulcerative colitis.<br><br>FUNDING: St Vincent's Clinic Foundation, Gastroenterological Society of Australia, Gutsy Group.}, }
@article {pmid34863329, year = {2022}, author = {Fischer, M and Khoruts, A}, title = {Oral lyophilised microbiota for the treatment of ulcerative colitis.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {7}, number = {2}, pages = {108-109}, doi = {10.1016/S2468-1253(21)00433-7}, pmid = {34863329}, issn = {2468-1253}, mesh = {*Colitis, Ulcerative/drug therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid34862475, year = {2021}, author = {Luo, H and Wu, H and Wang, L and Xiao, S and Lu, Y and Liu, C and Yu, X and Zhang, X and Wang, Z and Tang, L}, title = {Hepatoprotective effects of Cassiae Semen on mice with non-alcoholic fatty liver disease based on gut microbiota.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {1357}, pmid = {34862475}, issn = {2399-3642}, mesh = {Animals ; Cassia/*chemistry ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Liver/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/*drug therapy ; Plant Extracts/chemistry/*pharmacology ; Protective Agents/chemistry/*pharmacology ; Random Allocation ; Seeds/chemistry ; }, abstract = {Cassiae Semen (CS), the seeds of Cassia obtusifolia L. and C. tora L, have a long medicinal history in China, with suggestions for it to relieve constipation and exert hepatoprotective effects. However, the underlying mechanisms are still unclear. In this study, mice with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) were used to study the hepatoprotective effects of CS. The relationship between gut microbiota and hepatoprotective effect mechanisms mediated by CS extracts, the total aglycone extracts of CS, rubrofusarin-6-β-gentiobioside, and aurantio-obtusin were examined. Our data indicate that CS extracts and components confer a protective effect by ameliorating lipid accumulation, intestinal barrier damage, liver damage, and inflammation on HFD-induced liver injury. Meanwhile, fecal microbe transplantation exerted the pharmacological effect of CS on HFD-fed mice; however, the efficacy of CS was inhibited or eliminated by antibiotic-induced dysbiosis. In conclusion, the therapeutic effects of CS on NAFLD were closely related to the gut microbiota, suggesting a role for TCM in treating disease.}, }
@article {pmid34860566, year = {2021}, author = {Dickerson, JC and Ibeka, P and Inoyo, I and Oke, OO and Adewuyi, SA and Barry, D and Bello, A and Fasawe, O and Garrity, P and Habeebu, M and Huang, FW and Mulema, V and Nwankwo, KC and Remen, D and Wiwa, O and Bhatt, AS and Roy, M}, title = {Implementing Patient-Directed Cancer Education Materials Across Nigeria.}, journal = {JCO global oncology}, volume = {7}, number = {}, pages = {1610-1619}, pmid = {34860566}, issn = {2687-8941}, mesh = {Humans ; *Neoplasms/therapy ; Nigeria ; Palliative Care ; Pamphlets ; Poverty ; }, abstract = {PURPOSE: As access to cancer care expands in low-income countries, developing tools to educate patients is paramount. We took a picture booklet, which was initially developed by the nonprofit Global Oncology for Malawi and Rwanda, and adapted it for use in Nigeria. The primary goal was to assess acceptability and provide education. The secondary goals were (1) to describe the collaboration, (2) to assess knowledge gained from the intervention, (3) to assess patient understanding of their therapy intent, and (4) to explore patient's experiences via qualitative analysis.<br><br>METHODS: We piloted the original English booklet at a single site and requested feedback from patients and providers. The booklet was updated; translated into Hausa, Yoruba, Igbo, and Pidgin English; and used at three additional sites. For the three-site cohort, we collected basic demographics, pretest and post-test assessing content in the booklet, and performed a qualitative analysis.<br><br>RESULTS: The original booklet was widely acceptable and recommended by patients at site one (n = 31) and by providers (N = 26) representing all four sites. In the three-site cohort (n = 103), 94% of patients recommended the booklet. An immediate post-test focusing on when patients should present to care showed a statistically significant improvement in one of the seven questions. Fifty-one percent of the patients (n = 103) knew their treatment intent (curative v palliative). Qualitative analysis highlighted that the patient's thoughts on cancer are dominated by negative associations, although curability and modern therapy are also frequently cited.<br><br>CONCLUSION: We adapted an educational booklet to a novel context and had it delivered by local partners. The booklet was widely recommended to future patients. The booklet had an impact on patient's knowledge of cancer treatment, potentially allowing for decreased abandonment.}, }
@article {pmid34860453, year = {2022}, author = {Picciariello, A and Gallo, G and Sturiale, A and Litta, F and De Simone, V and Martines, G and Naldini, G and Ratto, C and Trompetto, M and Rinaldi, M}, title = {Clinical and functional outcome of surgery for posttraumatic cloacal deformity.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {24}, number = {4}, pages = {497-503}, doi = {10.1111/codi.16008}, pmid = {34860453}, issn = {1463-1318}, mesh = {Adult ; Anal Canal/surgery ; *Fecal Incontinence/etiology/surgery ; Female ; Humans ; Quality of Life ; Retrospective Studies ; Treatment Outcome ; }, abstract = {AIM: Cloacal deformity is a disabling condition that severely affects a patient's quality of life. Surgery to repair cloacal deformity remains the mainstay of treatment. The aim of this study is to assess the clinical and functional outcome of patients treated for traumatic cloacal deformity by three different techniques.<br><br>METHOD: A retrospective multicentre study was carried out using data from women operated on for cloacal deformity between 2015 and 2019. Demographic characteristics, the presence of urinary and/or faecal incontinence and manometric findings were collected. The main outcome measures were represented by St Mark's and Rockwood faecal incontinence quality of life scores.<br><br>RESULTS: Thirty eight women with a median age of 34&#xa0;years [interquartile range (IQR) 31-39&#xa0;years] were enrolled. Perineoplasty was performed in 23 patients by direct suture of the rectovaginal septum, in five using the X-flap and in 10 by the Singapore flap. Median resting and squeezing pressures increased significantly from 28.15 (IQR 23-32.7)&#xa0;cmH2 O to 45 (IQR 31-60.7) cmH2 O (p&#xa0;=&#xa0;0.0001) and from 47 (IQR 41.2-54.7)&#xa0;cmH2 O to 97.2 (IQR 80-118)&#xa0;cmH2 O (p&#xa0;=&#xa0;0.0001), respectively. Maximum tolerable volume improved from 120 (IQR 90-137.5)&#xa0;ml to 137.5 (IQR 120-150)&#xa0;ml (p&#xa0;=&#xa0;0.002). The St Mark's score decreased from 18 (IQR 14-20) to 4.5 (IQR 2-8) after 20&#xa0;months (p&#xa0;=&#xa0;0001). Sexual activity was confirmed by 16 patients preoperatively and by 27 postoperatively. A diverting stoma was performed in three patients after X-flap perineoplasty and in 14 treated by direct closure. No significant differences were found pre- and postoperatively between the three groups.<br><br>CONCLUSION: Regardless of the technique used, surgical repair significantly improves both clinical and functional outcomes irrespective of the presence of a covering stoma.}, }
@article {pmid34860235, year = {2021}, author = {Lu, X and Jing, Y and Li, Y and Zhang, N and Zhang, W and Cao, Y}, title = {The differential modulatory effects of Eurotium cristatum on the gut microbiota of obese dogs and mice are associated with improvements in metabolic disturbances.}, journal = {Food &amp; function}, volume = {12}, number = {24}, pages = {12812-12825}, doi = {10.1039/d1fo02886c}, pmid = {34860235}, issn = {2042-650X}, mesh = {Animals ; Aspergillus/*metabolism ; Diet, High-Fat ; Disease Models, Animal ; Dogs ; Gastrointestinal Microbiome/*drug effects ; Male ; Metabolic Diseases/drug therapy/*metabolism ; Mice ; Mice, Obese ; Obesity/drug therapy/*metabolism ; }, abstract = {Obesity is a disease in humans and companion animals that can cause many chronic diseases. Eurotium cristatum (E. cristatum) is a dominant fungus in Fuzhuan tea. In this study, we aimed to investigate the possibility that E. cristatum may reduce diet-induced obesity by regulating the gut microbiota and measuring the differences in the gut microbiota of obese mice and dogs under E. cristatum supplementation. High-fat diet-fed C57BL/6J mice and beagle dogs were supplemented with live E. cristatum for 8 or 12 weeks. Faecal microbiota transplantation (FMT) and 16S rRNA sequencing were used to evaluate the relationship between the anti-obesity effect of E. cristatum and the gut microbiota. The results suggested that live E. cristatum reduced obesity and metabolic disorders in obese mice and dogs. 16S rRNA sequencing results revealed that E. cristatum decreased the Firmicutes/Bacteroidetes (F/B) ratio and the abundance of members of the Firmicutes phylum, including Lactobacillus gasseri, Lactobacillus reuteri, and Lactobacillus intestinalis, in obese mice, but the opposite was true in obese dogs. Furthermore, to investigate whether the antiobesity effect of E. cristatum can be attributed to gut microbiota, FMT and 16S rRNA sequencing were employed. The FMT trial confirmed that the anti-obesity effect of E. cristatum was mediated by modulating gut dysbiosis. In addition, we isolated live E. cristatum from faeces and found the β-hydroxy acid metabolite of monacolin K (MKA) in E. cristatum culture. Our research implies that E. cristatum has the potential to treat obesity as a novel probiotic.}, }
@article {pmid34856844, year = {2021}, author = {Delaroque, C and Chervy, M and Gewirtz, AT and Chassaing, B}, title = {Social overcrowding impacts gut microbiota, promoting stress, inflammation, and dysglycemia.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {2000275}, pmid = {34856844}, issn = {1949-0984}, support = {R01 DK083890/DK/NIDDK NIH HHS/United States ; R01 DK099071/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Blood Glucose/metabolism ; Corticosterone/metabolism ; Crowding/*psychology ; Cytokines/metabolism ; Dysbiosis/metabolism/microbiology/psychology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Gastrointestinal Tract/metabolism/microbiology ; Hyperglycemia/microbiology ; Inflammation ; Mice ; Stress, Psychological/*metabolism/*microbiology/psychology/therapy ; }, abstract = {An array of chronic inflammatory diseases, including metabolic diseases such as obesity and diabetes, are thought to be promoted by disturbance of the intestinal microbiota. Such diseases disproportionately impact low-income communities, which are frequently afflicted by chronic stress and increased density housing. Hence, we hypothesized that overcrowded housing might promote stress, microbiota dysbiosis, inflammation, and, consequently, metabolic diseases. We tested this hypothesis in a tractable murine model of social overcrowding (SOC), in which mice were housed at twice normal density. SOC moderately impacted behavior in some widely used assays (Open Field, Elevated Plus Maze and Light/Dark tests) and resulted in a stark increase in corticosterone levels. Such indices of stress were associated with mild chronic gut inflammation, hyperglycemia, elevations in colonic cytokines, and alterations in gut microbiota composition. All of these consequences of SOC were eliminated by broad spectrum antibiotics, while some (inflammation and hyperglycemia) were transmitted by microbiota transplantation from SOC mice to germfree mice housed at normal density. Altogether, these results suggest a central role for intestinal microbiota in driving stress, inflammation, and chronic diseases that are promoted by overcrowded housing.}, }
@article {pmid34855639, year = {2021}, author = {Gao, ZY and Cui, Z and Yan, YQ and Ning, LJ and Wang, ZH and Hong, J}, title = {Microbe-based management for colorectal cancer.}, journal = {Chinese medical journal}, volume = {134}, number = {24}, pages = {2922-2930}, pmid = {34855639}, issn = {2542-5641}, mesh = {*Colorectal Neoplasms/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; Tumor Microenvironment ; }, abstract = {Colorectal cancer (CRC) is one of the most prevalent, most lethal cancers in the world. Increasing evidence suggests that the intestinal microbiota is closely related to the pathogenesis and prognosis of CRC. The normal microbiota plays an essential role in maintaining gut barrier function and the immune microenvironment. Recent studies have identified carcinogenic bacteria such as enterotoxigenic Bacteroides fragilis (ETBF) and Streptococcus gallolyticus (S. gallolyticus), as well as protective bacterial such as Akkermansia muciniphila (A. muciniphila), as potential targets of CRC treatment. Gut microbiota modulation aims to restore gut dysbiosis, regulate the intestinal immune system and prevent from pathogen invasion, all of which are beneficial for CRC prevention and prognosis. The utility of probiotics, prebiotics, postbiotics, fecal microbiota transplantation and dietary inventions to treat CRC makes them novel microbe-based management tools. In this review, we describe the mechanisms involved in bacteria-derived colorectal carcinogenesis and summarized novel bacteria-related therapies for CRC. In summary, we hope to facilitate clinical applications of intestinal bacteria for preventing and treating CRC.}, }
@article {pmid34854953, year = {2022}, author = {Secombe, KR and Crame, EE and Tam, JSY and Wardill, HR and Gibson, RJ and Coller, JK and Bowen, JM}, title = {Intestinal toll-like receptor 4 knockout alters the functional capacity of the gut microbiome following irinotecan treatment.}, journal = {Cancer chemotherapy and pharmacology}, volume = {89}, number = {2}, pages = {275-281}, pmid = {34854953}, issn = {1432-0843}, mesh = {Animals ; Cell Line, Tumor ; Colorectal Neoplasms/*drug therapy/genetics ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Diseases/chemically induced/microbiology ; Gastrointestinal Microbiome/*drug effects/genetics ; Irinotecan/*pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; RNA, Ribosomal, 16S ; Toll-Like Receptor 4/*genetics ; Topoisomerase I Inhibitors/pharmacology ; }, abstract = {PURPOSE: Irinotecan can cause high levels of diarrhea caused by toxic injury to the gastrointestinal microenvironment. Toll-like receptor 4 (TLR4) and the gut microbiome have previously been implicated in gastrointestinal toxicity and diarrhea; however, the link between these two factors has not been definitively determined. We used a tumor-bearing, intestinal epithelial cell (IEC) TLR4 knockout model (Tlr4[ΔIEC]) to assess microbiome changes following irinotecan treatment. We then determined if a fecal microbiota transplant (FMT) between Tlr4[ΔIEC] and wild-type (WT) mice altered irinotecan-induced gastrointestinal toxicity.<br><br>METHODS: MC-38 colorectal cancer cells were injected into WT and Tlr4[&#x394;IEC] mice. Fecal samples were collected prior to tumor inoculation, prior to irinotecan treatment and at cull. 16S rRNA gene sequencing was used to assess changes in the microbiome. Next, FMT was used to transfer the&#xa0;microbiome phenotype between Tlr4[&#x394;IEC] and WT mice prior to irinotecan treatment. Gastrointestinal toxicity symptoms were assessed.<br><br>RESULTS: In study 1, there were no compositional differences in the microbiome between Tlr4[&#x394;IEC] and WT mice at baseline. However, predicted functional capacity of the microbiome was different between WT and Tlr4[&#x394;IEC] at baseline and post-irinotecan. In study 2, Tlr4[&#x394;IEC] mice were protected from grade 3 diarrhea. Additionally, WT mice who did not receive FMT had more colonic damage in the colon compared to controls (P&#x2009;=&#x2009;0.013). This was not seen in Tlr4[&#x394;IEC] mice or WT mice who received FMT (P&#x2009;>&#x2009;0.05).<br><br>CONCLUSION: Tlr4[&#x394;IEC] and WT had no baseline compositional microbiome differences, but functional differences at baseline and following irinotecan. FMT altered some aspects of irinotecan-induced gastrointestinal toxicity.}, }
@article {pmid34854884, year = {2022}, author = {Dodiya, HB and Lutz, HL and Weigle, IQ and Patel, P and Michalkiewicz, J and Roman-Santiago, CJ and Zhang, CM and Liang, Y and Srinath, A and Zhang, X and Xia, J and Olszewski, M and Zhang, X and Schipma, MJ and Chang, EB and Tanzi, RE and Gilbert, JA and Sisodia, SS}, title = {Gut microbiota-driven brain Aβ amyloidosis in mice requires microglia.}, journal = {The Journal of experimental medicine}, volume = {219}, number = {1}, pages = {}, pmid = {34854884}, issn = {1540-9538}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R25 GM066522/GM/NIGMS NIH HHS/United States ; T32 HD007009/HD/NICHD NIH HHS/United States ; /ALZ/Alzheimer's Association/United States ; }, mesh = {Amyloid beta-Peptides/*metabolism ; Amyloidosis/genetics/*metabolism ; Animals ; Antibodies/administration &amp; dosage ; Brain/drug effects/*metabolism ; Chemokines/blood/genetics/metabolism ; Cytokines/blood/genetics/metabolism ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/drug effects/genetics/*physiology ; Gene Expression Profiling/methods ; Gene Ontology ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Microglia/*metabolism ; RNA-Seq/methods ; Sex Factors ; Mice ; }, abstract = {We previously demonstrated that lifelong antibiotic (ABX) perturbations of the gut microbiome in male APPPS1-21 mice lead to reductions in amyloid β (Aβ) plaque pathology and altered phenotypes of plaque-associated microglia. Here, we show that a short, 7-d treatment of preweaned male mice with high-dose ABX is associated with reductions of Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes at 9 wk of age in male mice only. More importantly, fecal microbiota transplantation (FMT) from transgenic (Tg) or WT male donors into ABX-treated male mice completely restored Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes. Transcriptomic studies revealed significant differences between vehicle versus ABX-treated male mice and FMT from Tg mice into ABX-treated mice largely restored the transcriptome profiles to that of the Tg donor animals. Finally, colony-stimulating factor 1 receptor (CSF1R) inhibitor-mediated depletion of microglia in ABX-treated male mice failed to reduce cerebral Aβ amyloidosis. Thus, microglia play a critical role in driving gut microbiome-mediated alterations of cerebral Aβ deposition.}, }
@article {pmid34853754, year = {2021}, author = {Jena, R and Jain, R and Muralidharan, S and Yanamala, VL and Zubair, Z and Kantamaneni, K and Jalla, K and Renzu, M and Alfonso, M}, title = {Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Parkinson's Disease.}, journal = {Cureus}, volume = {13}, number = {10}, pages = {e19035}, pmid = {34853754}, issn = {2168-8184}, abstract = {Parkinson's disease (PD) is one of the most common neurodegenerative diseases with a high rate of morbidity. It is associated with dopaminergic neuron loss and is fairly common in the elderly population. Recently, there has been a growing interest in the role of the gut microbiome in the pathogenesis of PD and thus studies addressing the methods to modulate the microbiota are becoming increasingly popular. Fecal microbiota transplant (FMT) is one of these methods and is effective in certain intestinal and extraintestinal conditions. This review aims to talk about gastrointestinal dysbiosis and how the reconstruction of this microbiome via FMT could potentially be used as a treatment modality in the future. We went through various studies and collected data relevant to our topic from the previous five years. The studies selected include reviews, observational studies, animal studies, case reports, and some grey literature. We concluded that although it has great potential as a therapeutic modality in the future, it is limited by several factors such as variability among the results of most clinical studies and the lack of large sample sizes. Therefore, there is a need for high-quality clinical trials with larger sample sizes to gather enough clinical evidence so that FMT can qualify as a widely recommended therapeutic measure.}, }
@article {pmid34853526, year = {2021}, author = {Chen, HL and Zeng, YB and Zhang, ZY and Kong, CY and Zhang, SL and Li, ZM and Huang, JT and Xu, YY and Mao, YQ and Cai, PR and Han, B and Wang, WQ and Wang, LS}, title = {Gut and Cutaneous Microbiome Featuring Abundance of Lactobacillus reuteri Protected Against Psoriasis-Like Inflammation in Mice.}, journal = {Journal of inflammation research}, volume = {14}, number = {}, pages = {6175-6190}, pmid = {34853526}, issn = {1178-7031}, abstract = {BACKGROUND: Psoriasis is a chronic autoinflammatory skin disease, and its aetiology remains incompletely understood. Recently, gut microbial dysbiosis is found to be tightly associated with psoriasis.<br><br>OBJECTIVE: We sought to reveal the causal role of gut microbiota dysbiosis in psoriasis pathogenesis and investigate the protective effect of healthy commensal bacteria against imiquimod -induced psoriasis-like skin response.<br><br>METHODS: By using fecal microbial transplantation (FMT), 16S rRNA gene-based taxonomic profiling and Lactobacillus supplement, we have assessed the effect of FMT from healthy individuals on psoriasis-like skin inflammation and associated immune disorders in imiquimod-induced psoriasis mice.<br><br>RESULTS: Here, by using psoriasis mice humanized with the stools from healthy donors and psoriasis patients, the imiquimod-induced psoriasis in mice with psoriasis patient stool was found to be significantly aggravated as compared to the mice with healthy donor stools. Further analysis showed fecal microbiota of healthy individuals protected against Treg/Th17 imbalance in psoriasis. Moreover, we found the gut and skin microbiome in mice receipted with gut microbiota of healthy individuals (HD) differed from those of mice receipted with gut microbiota of psoriasis patients (PSD). 16S rRNA sequencing revealed that Lactobacillus reuteri was greatly enriched in fecal and cutaneous microbiome of HD mice as compared to PSD mice. Intriguingly, supplement with Lactobacillus reuteri was sufficient to increase the expression of anti-inflammatory gene IL-10, reduce Th17 cells counts and confer resistance to imiquimod-induced inflammation on the mice with gut microbiota dysbiosis.<br><br>CONCLUSION: Our results suggested that the gut microbiota dysbiosis is the potential causal factor for psoriasis and the gut microbiota may serve as promising therapy target for psoriasis patients.}, }
@article {pmid34853336, year = {2021}, author = {Natarajan, A and Han, A and Zlitni, S and Brooks, EF and Vance, SE and Wolfe, M and Singh, U and Jagannathan, P and Pinsky, BA and Boehm, A and Bhatt, AS}, title = {Publisher Correction: Standardized preservation, extraction and quantification techniques for detection of fecal SARS-CoV-2 RNA.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {7100}, doi = {10.1038/s41467-021-27392-4}, pmid = {34853336}, issn = {2041-1723}, }
@article {pmid34852831, year = {2021}, author = {Xie, L and Xu, C and Fan, Y and Li, Y and Wang, Y and Zhang, X and Yu, S and Wang, J and Chai, R and Zhao, Z and Jin, Y and Xu, Z and Zhao, S and Bian, Y}, title = {Effect of fecal microbiota transplantation in patients with slow transit constipation and the relative mechanisms based on the protein digestion and absorption pathway.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {490}, pmid = {34852831}, issn = {1479-5876}, support = {ZC20097//Tianjin Municipal Health Bureau/ ; 2020YJ017//tianjin union medical center/ ; 2017YJZD005//tianjin union dedical center/ ; 81873100//National Natural Science Foundation of China/ ; No.82174374//National Natural Science Foundation of China/ ; }, mesh = {Constipation/therapy ; *Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Proteolysis ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is considered an effective treatment for slow transit constipation (STC); nevertheless, the mechanism remains unclear.<br><br>METHODS: In this study, eight patients with STC were selected according to the inclusion and exclusion criteria; they then received three treatments of FMT. The feces and serum of STC patients were collected after each treatment and analyzed by integrating 16&#xa0;s rRNA microbiome and metabolomic analyses.<br><br>RESULTS: The results showed that the percentage of clinical improvement reached 62.5% and the rates of patients' clinical remission achieved 75% after the third treatment. At the same time, FMT improved the Wexner constipation scale (WCS), the Gastrointestinal Quality-of-Life Index (GIQLI) and Hamilton Depression Scale (HAMD). Fecal microbiome alpha diversity and beta diversity altered significantly after FMT. Analysis of the 16&#xa0;s rRNA microbiome showed that the numbers of Bacteroidetes (Prevotell/Bacteroides) and Firmicute (Roseburia/Blautia) decreased, whereas Actinobacteria (Bifidobacterium), Proteobacteria (Escherichia), and Firmicute (Lactobacillus) increased after FMT. The metabolomics analyses showed that the stool of FMT-treated patients were characterized by relatively high levels of N-Acetyl-L-glutamate, gamma-L-glutamyl-L-glutamic acid, Glycerophosphocholine, et al., after FMT. Compared with baseline, the serum of treated patients was characterized by relatively high levels of L-Arginine, L-Threonine, Ser-Arg, Indoleacrylic acid, Phe-Tyr, 5-L-Glutamyl-L-alanine, and lower levels of Erucamide after the treatment. The correlation analysis between the metabolites and gut microbiota showed a significant correlation. For example, L-Arginine was positively correlated with lactobacillus, et al. L-Threonine was positively correlated with Anaerovibrio, Sediminibacterium but negatively correlated with Phascolarctobacterium. Erucamide had significant negative correlations with Sediminibacterium and Sharpea, while being positively correlated with Phascolarctobacterium. Enriched KEGG pathways analysis demonstrated that the protein digestion and absorption pathways gradually upregulated with the increase of FMT frequency. The L-Arginine and L-Threonine were also involved in the pathway. A large amount of Na&#x2009;+&#x2009;was absorbed in the pathway, so that it might increase mucus secretion and electrical excitability of GI smooth muscle.<br><br>CONCLUSIONS: Therefore, we speculated that FMT changed the patients' gut microbiota and metabolites involved in the protein digestion and absorption pathways, thereby improving the symptoms of STC. Study on the effectiveness and safety of FMT in the treatment of STC. The study was reviewed and approved by Ethics Committee of Tianjin People's Hospital (ChiCTR2000033227) in 2020.}, }
@article {pmid34846698, year = {2021}, author = {Wu, LH and Ye, ZN and Peng, P and Xie, WR and Xu, JT and Zhang, XY and Xia, HH and He, XX}, title = {Efficacy and Safety of Washed Microbiota Transplantation to Treat Patients with Mild-to-Severe COVID-19 and Suspected of Having Gut Microbiota Dysbiosis: Study Protocol for a Randomized Controlled Trial.}, journal = {Current medical science}, volume = {41}, number = {6}, pages = {1087-1095}, pmid = {34846698}, issn = {2523-899X}, mesh = {Adult ; Aged ; COVID-19/complications/*microbiology/*therapy ; China ; Clinical Protocols ; Dysbiosis/etiology/*microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; *Gastrointestinal Microbiome ; Humans ; Living Donors ; Male ; Middle Aged ; Prospective Studies ; *SARS-CoV-2 ; Safety ; Single-Blind Method ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Coronavirus disease 2019 (COVID-19) is often accompanied by gastrointestinal symptoms, which are related to gut microbiota dysbiosis (GMD). Whether washed microbiota transplantation (WMT) is an effective treatment for COVID-19 patients suspected of having GMD by restoring the gut microbiota is unknown. This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected of having GMD.<br><br>METHODS: This is a randomized, multicenter, single-blind prospective study. COVID-19 patients suspected of having GMD will be randomly divided to receive routine treatment only or to receive routine treatment and WMT. The frequency of WMT will be once a day for three consecutive days. Laboratory and imaging examinations will be performed at admission, 1 and 2 weeks after treatment, and on the day of discharge. Then a telephone follow-up will be conducted at 1st week, 2nd week, and 6th month after discharge. The clinical efficacy and safety of WMT in COVD-19 patients suspected of having GMD and the effects of WMT on the organ function, homeostasis, inflammatory response, intestinal mucosal barrier function, and immunity of the patients will be evaluated.<br><br>RESULTS: By following the proposed protocol, WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected of having GMD, and the therapeutic effect is expected to be associated with improvement of the intestinal mucosal barrier function, inflammatory response, and immunity.<br><br>CONCLUSION: The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD.}, }
@article {pmid34846164, year = {2021}, author = {Dilmore, AH and McDonald, D and Nguyen, TT and Adams, JB and Krajmalnik-Brown, R and Elijah, E and Dorrestein, PC and Knight, R}, title = {The Fecal Microbiome and Metabolome of Pitt Hopkins Syndrome, a Severe Autism Spectrum Disorder.}, journal = {mSystems}, volume = {6}, number = {6}, pages = {e0100621}, pmid = {34846164}, issn = {2379-5077}, support = {K23 MH118435/MH/NIMH NIH HHS/United States ; //Pitt Hopkins Research Foundation (PHRF)/ ; K23 MH118435/MH/NIMH NIH HHS/United States ; }, abstract = {Alterations to the gut microbiome have been reported between children with autism spectrum disorders (ASDs) and typically developing (TD) children. Characterizing these differences has led to the proposal of new treatments for ASD, such as probiotic interventions and fecal matter transplants. However, no study to date has characterized the gut microbiome or metabolome in Pitt Hopkins syndrome (PTHS), a severe ASD with a high incidence of gastrointestinal (GI) disturbances such as constipation. Here, we surveyed the gut microbiome and metabolome in a cohort of PTHS individuals and their unaffected parents. We focused our analysis on Clostridium bolteae, a microbe previously associated with ASD known to chemically modify bile acids in the gut. PTHS individuals carry a higher load of C. bolteae than their parents as well as both ASD and non-ASD individuals from the American Gut Project cohort. Specific metabolites were associated with PTHS, including bile acids and sphingosines. With a metadata reanalysis tool, we found that PTHS-associated metabolites have previously been identified in inflammatory bowel disease and obesity patients. These results suggest microbial involvement in PTHS, but further research must be performed to clarify the exact mechanisms through which microbes may act. Furthermore, new associations between PTHS-specific metabolites and other conditions may lead to additional therapeutic options for PTHS individuals. IMPORTANCE GI disturbances in ASD such as severe constipation can be medically significant and often require medication. This is especially true for individuals with PTHS, suggesting that the gut microbiome may be involved in PTHS's pathology. Revealing associations between specific gut microbes and PTHS may allow the development of new therapeutics or the application of existing therapeutics to ease day-to-day challenges encountered by PTHS individuals. In this study, we characterized an association between C. bolteae and PTHS, in addition to metabolites linked to both PTHS and C. bolteae. We also identified other microbiome-involved medical conditions where PTHS-associated metabolites have been isolated. Utilizing common metabolites to identify conditions with similar phenotypes may suggest new therapeutic options for GI-related symptoms.}, }
@article {pmid34841787, year = {2021}, author = {Wei, K and Chen, T}, title = {[Vaginal microbiota transplantation for treatment of bacterial vaginosis: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3820-3827}, doi = {10.13345/j.cjb.210163}, pmid = {34841787}, issn = {1872-2075}, mesh = {Dysbiosis/therapy ; Female ; Humans ; *Microbiota ; Vagina ; *Vaginosis, Bacterial/therapy ; }, abstract = {Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. The conventional antibiotic treatment can aggravate microbial dysbiosis, alter the acid environment of the vagina and lead to drug resistance, thus shows low cure rate and high recurrence rate. This poses significant physiological and psychological burden to the BV patients. Vaginal microbiota transplantation (VMT) is a novel live biotherapeutic approach. It directly engrafts the whole vaginal microbiota from healthy women to the vaginal tract of patients to rapidly reconstruct the vaginal microbiota environment and restore the vaginal health. This article summarizes the development, present challenges, and future directions of using VMT, with the aim to explore new strategies for treatment of BV and promote the clinical use of VMT.}, }
@article {pmid34841786, year = {2021}, author = {Zhang, M and Wang, H and Xue, L and Yang, X}, title = {[Advances in fecal microbiota transplantation for treatment of Parkinson's disease].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3812-3819}, doi = {10.13345/j.cjb.200770}, pmid = {34841786}, issn = {1872-2075}, mesh = {Aged ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Middle Aged ; *Neurodegenerative Diseases ; *Parkinson Disease/therapy ; }, abstract = {Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Patients with PD often suffer from gastrointestinal symptoms in the early stage of the disease. Several studies have confirmed that gut microbiota is involved in the progress of PD. As one of the most effective ways to reconstruct the gut microbiota, fecal microbiota transplantation (FMT) has shown potential therapeutic effects on PD. This review summarizes the basic and clinical studies of FMT in the treatment of PD.}, }
@article {pmid34841783, year = {2021}, author = {Shen, X and Sun, Z}, title = {[Microbe-gut-brain axis and neurological disorders: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3781-3788}, doi = {10.13345/j.cjb.200773}, pmid = {34841783}, issn = {1872-2075}, mesh = {Brain ; Environment ; *Gastrointestinal Microbiome ; Humans ; *Neurodegenerative Diseases ; }, abstract = {Intestinal microbes have an adjuvant therapeutic effect on neurological disorders (such as Parkinson's, depression, and Alzheimer's disease). It affects brain function and host behavior through the neural pathways, the immune pathways and the microbial metabolites, the so-called gut-brain axis. This article summarizes the recent advances in the role of the microbe-gut-brain axis in neurological disorders, in order to provide new ideas for the treatment of neurodegenerative diseases.}, }
@article {pmid34841294, year = {2021}, author = {Hiltunen, H and Hanani, H and Luoto, R and Turjeman, S and Ziv, O and Isolauri, E and Salminen, S and Koren, O and Rautava, S}, title = {Preterm infant meconium microbiota transplant induces growth failure, inflammatory activation, and metabolic disturbances in germ-free mice.}, journal = {Cell reports. Medicine}, volume = {2}, number = {11}, pages = {100447}, pmid = {34841294}, issn = {2666-3791}, mesh = {Animals ; Cytokines/genetics/metabolism ; *Fecal Microbiota Transplantation ; Female ; Gene Expression Regulation ; *Germ-Free Life ; *Growth and Development ; Hormones/metabolism ; Humans ; Infant, Newborn ; Infant, Premature/*physiology ; Inflammation/genetics/*pathology ; Male ; Meconium/*microbiology ; *Metabolism/genetics ; Mice ; Weight Gain ; }, abstract = {Preterm birth may result in adverse health outcomes. Very preterm infants typically exhibit postnatal growth restriction, metabolic disturbances, and exaggerated inflammatory responses. We investigated the differences in the meconium microbiota composition between very preterm (<32 weeks), moderately preterm (32-37 weeks), and term (>37 weeks) human neonates by 16S rRNA gene sequencing. Human meconium microbiota transplants to germ-free mice were conducted to investigate whether the meconium microbiota is causally related to the preterm infant phenotype in an experimental model. Our results indicate that very preterm birth is associated with a distinct meconium microbiota composition. Fecal microbiota transplant of very preterm infant meconium results in impaired growth, altered intestinal immune function, and metabolic parameters as compared to term infant meconium transplants in germ-free mice. This finding suggests that measures aiming to minimize the long-term adverse consequences of very preterm birth should be commenced during pregnancy or directly after birth.}, }
@article {pmid34840686, year = {2021}, author = {Gunardi, TH and Susantono, DP and Victor, AA and Sitompul, R}, title = {Atopobiosis and Dysbiosis in Ocular Diseases: Is Fecal Microbiota Transplant and Probiotics a Promising Solution?.}, journal = {Journal of ophthalmic &amp; vision research}, volume = {16}, number = {4}, pages = {631-643}, pmid = {34840686}, issn = {2008-2010}, abstract = {PURPOSE: To highlight the role of atopobiosis and dysbiosis in the pathomechanism of autoimmune uveitis, therefore supporting fecal microbiota transplant (FMT) and probiotics as potential targeted-treatment for uveitis.<br><br>METHODS: This review synthesized literatures upon the relation between gut microbiota, autoimmune uveitis, FMT, and probiotics, published from January 2001 to March 2021 and indexed in PubMed, Google Scholar, CrossRef.<br><br>RESULTS: The basis of the gut-eye axis revolves around occurrences of molecular mimicry, increase in pro-inflammatory cytokines, gut epithelial barrier disruption, and translocation of microbes to distant sites. In patients with autoimmune uveitis, an increase of gut Fusobacterium and Enterobacterium were found. With current knowledge of aforementioned mechanisms, studies modifying the gut microbiome and restoring the physiologic gut barrier has been the main focus for pathomechanism-based therapy. In mice models, FMT and probiotics targeting repopulation of gut microbiota has shown significant improvement in clinical manifestations of uveitis. Consequently, a better understanding in the homeostasis of gut microbiome along with their role in the gut-eye axis is needed to develop practical targeted treatment.<br><br>CONCLUSION: Current preliminary studies are promising in establishing a causative gut-eye axis relationship and the possibility of conducting FMT and probiotics as targeted treatment to mitigate autoimmune uveitis, to shorten disease duration, and to prevent further complications.}, }
@article {pmid34838850, year = {2022}, author = {Chen, L and Li, R and Wang, Z and Zhang, Z and Wang, J and Qiao, Y and Huang, Y and Liu, W}, title = {Lactate-utilizing bacteria ameliorates DSS-induced colitis in mice.}, journal = {Life sciences}, volume = {288}, number = {}, pages = {120179}, doi = {10.1016/j.lfs.2021.120179}, pmid = {34838850}, issn = {1879-0631}, mesh = {Adult ; Animals ; Bacteria/*growth &amp; development ; Colitis/chemically induced/microbiology/pathology/*prevention &amp; control ; Dextran Sulfate/*toxicity ; Dysbiosis/chemically induced/microbiology/pathology/prevention &amp; control ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Humans ; Lactic Acid/*metabolism ; Male ; Mice, Inbred C57BL ; Probiotics/*administration &amp; dosage ; Young Adult ; Mice ; }, abstract = {Inflammatory bowel diseases (IBD) stem from alterations in the intestinal immune system and microbial dysbiosis, but the precise interactions between bacteria and IBD remain obscure. The commensal microbiota have a profound impact on human health and diseases. Here, we developed a selective culture medium for lactate-utilizing bacteria (LUB) that function as candidate probiotics to ameliorate IBD using a mouse model. Firstly, LUB, including Megasphaera, were enriched from human faeces using a selective medium with lactate. LUB efficiently attenuated the pathology of colitis induced by dextran sulphate sodium (DSS). Next, LUB administration counteracted the dysbiosis associated with the intestinal inflammatory process, and elevated the proportion of Escherichia-Shigella in intestines. Moreover, E. coli isolated from healthy faeces downstream recapitulated lactate-utilizing bacterial community to ameliorate the severity of DSS-induced acute colitis. In conclusion, our finding revealed that LUB were sufficient to exert inflammatory protection against colitis in mice, highlighting a novel therapeutic strategy to use LUB as potentially curable probiotics for therapeutic manipulation for IBD.}, }
@article {pmid34838016, year = {2021}, author = {He, J and He, X and Ma, Y and Yang, L and Fang, H and Shang, S and Xia, H and Lian, G and Tang, H and Wang, Q and Wang, J and Lin, Z and Wen, J and Liu, Y and Zhai, C and Wang, W and Jiang, X and Xuan, J and Liu, M and Lu, S and Li, X and Wang, H and Ouyang, C and Cao, M and Lin, A and Zhang, B and Wu, D and Chen, Y and Xiao, C}, title = {A comprehensive approach to stool donor screening for faecal microbiota transplantation in China.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {216}, pmid = {34838016}, issn = {1475-2859}, support = {81730003//national natural science foundation of china/ ; 82004433//national natural science foundation of china/ ; 2017ZX09304021//national major science and technology projects of china/ ; 16CZX064//national office for philosophy and social sciences/ ; }, mesh = {Adolescent ; Adult ; China ; Clostridium Infections/therapy ; Computational Biology/methods ; Donor Selection/*methods ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Male ; Metagenomics/*methods ; Retrospective Studies ; *Tissue Donors ; Young Adult ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China.<br><br>RESULTS: The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time.<br><br>CONCLUSIONS: DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective&#xa0;study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT.}, }
@article {pmid34836663, year = {2022}, author = {Lee, PC and Chang, TE and Wang, YP and Lee, KC and Lin, YT and Chiou, JJ and Huang, CW and Yang, UC and Li, FY and Huang, HC and Wu, CY and Huang, YH and Hou, MC}, title = {Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {121}, number = {9}, pages = {1636-1646}, doi = {10.1016/j.jfma.2021.11.001}, pmid = {34836663}, issn = {0929-6646}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Phylogeny ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND/PURPOSE: Clostridium difficile infection (CDI) leads to a significant cause of hospital-acquired morbidity and mortality. Fecal microbiota transplantation (FMT) is effective to treat recurrent or refractory CDI (rCDI). However, the change of microbial composition contributed by FMT and its association with treatment outcomes is not well determined in Taiwan. We aimed to investigate the efficacy of FMT and the association with microbial alteration endemically.<br><br>METHODS: Twelve patients who received FMT for rCDI in Taipei Veterans General Hospital were prospectively enrolled from April 2019 to July 2020. The clinical assessments and fecal microbial analyses in comparison with fecal materials of unrelated donors were conducted before and after FMT.<br><br>RESULTS: The overall success rate of FMT for rCDI was 91.7%. A prominence of Proteobacteria, Gammaproteobacteria and Enterobacteriales were observed in the feces of patients with rCDI. Increased fecal phylogenetic diversities and a significant microbial dissimilarity were provided by successful FMT compared to patients before treatment. However, the distinctness was not obvious between patients' feces at baseline and after unsuccessful FMT. Moreover, dynamic change of fecal microbial composition after FMT was observed during follow-up but did not interrupt the treatment effects of FMT.<br><br>CONCLUSION: Gut dysbiosis commonly co-exists in patients with rCDI. Restoration of gut microbial communities by FMT provides a promising strategy to treat antibiotic-failed CDI, and the extent of microbial change would be related to the treatment outcomes of FMT. Besides, the effectiveness of FMT for CDI could be maintained even the gut microbiota has diverged over time.}, }
@article {pmid34835981, year = {2021}, author = {Houron, C and Ciocan, D and Trainel, N and Mercier-Nomé, F and Hugot, C and Spatz, M and Perlemuter, G and Cassard, AM}, title = {Gut Microbiota Reshaped by Pectin Treatment Improves Liver Steatosis in Obese Mice.}, journal = {Nutrients}, volume = {13}, number = {11}, pages = {}, pmid = {34835981}, issn = {2072-6643}, support = {CT0069291-01//Servier (France)/ ; DEQ-20170336743//Fondation pour la Recherche M&#xe9;dicale/ ; }, mesh = {Adipose Tissue, White/pathology ; Animals ; Diet, High-Fat ; Fatty Liver/*microbiology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Male ; Mice, Inbred C57BL ; Mice, Obese ; Pectins/*pharmacology ; Mice ; }, abstract = {Pectin, a soluble fiber, improves non-alcoholic fatty-liver disease (NAFLD), but its mechanisms are unclear. We aimed to investigate the role of pectin-induced changes in intestinal microbiota (IM) in NAFLD. We recovered the IM from mice fed a high-fat diet, treated or not with pectin, to perform a fecal microbiota transfer (FMT). Mice fed a high-fat diet, which induces NAFLD, were treated with pectin or received a fecal microbiota transfer (FMT) from mice treated with pectin before (preventive FMT) or after (curative FMT) being fed a high-fat diet. Pectin prevented the development of NAFLD, induced browning of adipose tissue, and modified the IM without increasing the abundance of proteobacteria. Preventive FMT also induced browning of white adipose tissue but did not improve liver steatosis, in contrast to curative FMT, which induced an improvement in steatosis. This was associated with an increase in the concentration of short-chain fatty acids (SCFAs), in contrast to preventive FMT, which induced an increase in the concentration of branched SCFAs. Overall, we show that the effect of pectin may be partially mediated by gut bacteria.}, }
@article {pmid34835424, year = {2021}, author = {Zanella, MC and Pastor, D and Feltkamp, MCW and Hadaya, K and Cordey, S and Toutous Trellu, L}, title = {Sustained Trichodysplasia Spinulosa Polyomavirus Viremia Illustrating a Primary Disseminated Infection in a Kidney Transplant Recipient.}, journal = {Microorganisms}, volume = {9}, number = {11}, pages = {}, pmid = {34835424}, issn = {2076-2607}, abstract = {Novel human polyomaviruses (HPyV) have been recently identified in solid organ transplant recipients. Trichodysplasia spinulosa (TS) is a rare disease associated with immunosuppression and induced by a polyomavirus (TSPyV). We report here a case of primary and disseminated TSPyV infection after kidney transplantation with extensive skin lesions, sustained viremia, and high viral loads in urine specimens, anal, nasal and throat swabs, assessed via specific real-time PCR for TSPyV during a follow-up period of 32 months after transplantation. The detection of TSPyV with a high viral load in respiratory and anal swab samples is compatible with viral replication and thus may suggest potential respiratory and oro-fecal routes of transmission.}, }
@article {pmid34835406, year = {2021}, author = {Sun, P and Su, L and Zhu, H and Li, X and Guo, Y and Du, X and Zhang, L and Qin, C}, title = {Gut Microbiota Regulation and Their Implication in the Development of Neurodegenerative Disease.}, journal = {Microorganisms}, volume = {9}, number = {11}, pages = {}, pmid = {34835406}, issn = {2076-2607}, abstract = {In recent years, human gut microbiota have become one of the most promising areas of microorganism research; meanwhile, the inter-relation between the gut microbiota and various human diseases is a primary focus. As is demonstrated by the accumulating evidence, the gastrointestinal tract and central nervous system interact through the gut-brain axis, which includes neuronal, immune-mediated and metabolite-mediated pathways. Additionally, recent progress from both preclinical and clinical studies indicated that gut microbiota play a pivotal role in gut-brain interactions, whereas the imbalance of the gut microbiota composition may be associated with the pathogenesis of neurological diseases (particularly neurodegenerative diseases), the underlying mechanism of which is insufficiently studied. This review aims to highlight the relationship between gut microbiota and neurodegenerative diseases, and to contribute to our understanding of the function of gut microbiota in neurodegeneration, as well as their relevant mechanisms. Furthermore, we also discuss the current application and future prospects of microbiota-associated therapy, including probiotics and fecal microbiota transplantation (FMT), potentially shedding new light on the research of neurodegeneration.}, }
@article {pmid34835132, year = {2021}, author = {Shirazi, R and Pozzi, P and Gozlan, Y and Wax, M and Lustig, Y and Linial, M and Mendelson, E and Bardenstein, S and Mor, O}, title = {Identification of Hepatitis E Virus Genotypes 3 and 7 in Israel: A Public Health Concern?.}, journal = {Viruses}, volume = {13}, number = {11}, pages = {}, pmid = {34835132}, issn = {1999-4915}, mesh = {Adult ; Animals ; Camelus ; Feces/virology ; Hepatitis Antibodies/*blood ; Hepatitis E/*virology ; Hepatitis E virus/*genetics ; Humans ; Israel ; Male ; Seroepidemiologic Studies ; Swine ; Swine Diseases/*virology ; Young Adult ; Zoonoses/*virology ; }, abstract = {BACKGROUND: Hepatitis E (HEV) is an emerging cause of viral hepatitis worldwide. Swine carrying hepatitis E genotype 3 (HEV-3) are responsible for the majority of chronic viral hepatitis cases in developed countries. Recently, genotype 7 (HEV-7), isolated from a dromedary camel in the United Arab Emirates, was also associated with chronic viral hepatitis in a transplant recipient. In Israel, chronic HEV infection has not yet been reported, although HEV seroprevalence in humans is ~10%. Camels and swine are >65% seropositive. Here we report on the isolation and characterization of HEV from local camels and swine.<br><br>METHODS: Sera from camels (n = 142), feces from swine (n = 18) and blood from patients suspected of hepatitis E (n = 101) were collected during 2017-2020 and used to detect and characterize HEV sequences.<br><br>RESULTS: HEV-3 isolated from local swine and the camel-derived HEV-7 sequence were highly similar to HEV-3f and HEV-7 sequences (88.2% and 86.4%, respectively) related to viral hepatitis. The deduced amino acid sequences of both isolates were also highly conserved (>98%). Two patients were HEV-RNA positive; acute HEV-1 infection could be confirmed in one of them.<br><br>DISCUSSION: The absence of any reported HEV-3 and HEV-7 infection in humans remains puzzling, especially considering the reported seroprevalence rates, the similarity between HEV sequences related to chronic hepatitis and the HEV genotypes identified in swine and camels in Israel.}, }
@article {pmid34831464, year = {2021}, author = {Palmieri, O and Castellana, S and Biscaglia, G and Panza, A and Latiano, A and Fontana, R and Guerra, M and Corritore, G and Latiano, T and Martino, G and Mazza, T and Andriulli, A and Perri, F and Bossa, F}, title = {Microbiome Analysis of Mucosal Ileoanal Pouch in Ulcerative Colitis Patients Revealed Impairment of the Pouches Immunometabolites.}, journal = {Cells}, volume = {10}, number = {11}, pages = {}, pmid = {34831464}, issn = {2073-4409}, support = {RICERCA CORRENTE//Ministero della Salute/ ; }, mesh = {Adult ; Biodiversity ; Colitis, Ulcerative/*microbiology ; Colonic Pouches/*immunology/*microbiology ; Entropy ; Female ; Humans ; Intestinal Mucosa/*microbiology ; Male ; *Metabolome ; *Microbiota/genetics ; Middle Aged ; Phylogeny ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics ; }, abstract = {UNLABELLED: The pathogenesis of ulcerative colitis (UC) is unknown, although genetic loci and altered gut microbiota have been implicated. Up to a third of patients with moderate to severe UC require proctocolectomy with ileal pouch ano-anastomosis (IPAA). We aimed to explore the mucosal microbiota of UC patients who underwent IPAA.<br><br>METHODS: For microbiome analysis, mucosal specimens were collected from 34 IPAA individuals. Endoscopic and histological examinations of IPAA were normal in 21 cases, while pouchitis was in 13 patients. 19 specimens from the healthy control (10 from colonic and 9 from ileum) were also analyzed. Data were analyzed using an ensemble of software packages: QIIME2, coda-lasso, clr-lasso, PICRUSt2, and ALDEx2.<br><br>RESULTS: IPAA specimens had significantly lower bacterial diversity as compared to normal. The microbial composition of the normal pouch was also decreased also when compared to pouchitis. Faecalibacterium prausnitzii, Gemmiger formicilis, Blautia obeum, Ruminococcus torques, Dorea formicigenerans, and an unknown species from Roseburia were the most uncommon in pouch/pouchitis, while an unknown species from Enterobacteriaceae was over-represented. Propionibacterium acnes and Enterobacteriaceae were the species most abundant in the pouchitis and in the normal pouch, respectively. Predicted metabolic pathways among the IPAA bacterial communities revealed an important role of immunometabolites such as SCFA, butyrate, and amino acids.<br><br>CONCLUSIONS: Our findings showed specific bacterial signature hallmarks of dysbiosis and could represent bacterial biomarkers in IPAA patients useful to develop novel treatments in the future by modulating the gut microbiota through the administration of probiotic immunometabolites-producing bacterial strains and the addition of specific prebiotics and the faecal microbiota transplantation.}, }
@article {pmid34831456, year = {2021}, author = {Monaghan, TM and Duggal, NA and Rosati, E and Griffin, R and Hughes, J and Roach, B and Yang, DY and Wang, C and Wong, K and Saxinger, L and Pučić-Baković, M and Vučković, F and Klicek, F and Lauc, G and Tighe, P and Mullish, BH and Blanco, JM and McDonald, JAK and Marchesi, JR and Xue, N and Dottorini, T and Acharjee, A and Franke, A and Li, Y and Wong, GK and Polytarchou, C and Yau, TO and Christodoulou, N and Hatziapostolou, M and Wang, M and Russell, LA and Kao, DH}, title = {A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection.}, journal = {Cells}, volume = {10}, number = {11}, pages = {}, pmid = {34831456}, issn = {2073-4409}, support = {MC_PC_12025/MRC_/Medical Research Council/United Kingdom ; ZI418//University of Alberta Hospital Foundation/ ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Animals ; Antibodies, Neutralizing/metabolism ; Bacterial Toxins/immunology ; Chlorocebus aethiops ; Clostridium Infections/immunology/microbiology/*therapy ; Cluster Analysis ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Genomics ; Humans ; Immunosenescence ; Male ; Middle Aged ; Phylogeny ; Receptors, Antigen, T-Cell/metabolism ; Time Factors ; Treatment Outcome ; Vero Cells ; }, abstract = {Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.}, }
@article {pmid34830388, year = {2021}, author = {Eindor-Abarbanel, A and Healey, GR and Jacobson, K}, title = {Therapeutic Advances in Gut Microbiome Modulation in Patients with Inflammatory Bowel Disease from Pediatrics to Adulthood.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830388}, issn = {1422-0067}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Colitis/microbiology/*therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*drug effects/genetics ; Humans ; Inflammatory Bowel Diseases/genetics/microbiology/pathology/*therapy ; Pediatrics ; Prebiotics ; Probiotics/*therapeutic use ; }, abstract = {There is mounting evidence that the gut microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD). For the past decade, high throughput sequencing-based gut microbiome research has identified characteristic shifts in the composition of the intestinal microbiota in patients with IBD, suggesting that IBD results from alterations in the interactions between intestinal microbes and the host's mucosal immune system. These studies have been the impetus for the development of new therapeutic approaches targeting the gut microbiome, such as nutritional therapies, probiotics, fecal microbiota transplant and beneficial metabolic derivatives. Innovative technologies can further our understanding of the role the microbiome plays as well as help to evaluate how the different approaches in microbiome modulation impact clinical responses in adult and pediatric patients. In this review, we highlight important microbiome studies in patients with IBD and their response to different microbiome modulation therapies, and describe the differences in therapeutic response between pediatric and adult patient cohorts.}, }
@article {pmid34830048, year = {2021}, author = {Bacci, G and Rossi, A and Armanini, F and Cangioli, L and De Fino, I and Segata, N and Mengoni, A and Bragonzi, A and Bevivino, A}, title = {Lung and Gut Microbiota Changes Associated with Pseudomonas aeruginosa Infection in Mouse Models of Cystic Fibrosis.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830048}, issn = {1422-0067}, support = {Grant FFC#19/2017//Italian Cystic Fibrosis Research Foundation (FFC)/ ; }, mesh = {Animals ; Body Weight ; Cystic Fibrosis/*metabolism/*microbiology ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Disease Models, Animal ; Dysbiosis/genetics/microbiology ; Feces/microbiology ; Gastrointestinal Tract/*metabolism/*microbiology ; Lung/*metabolism/*microbiology ; Mice ; Microbiota/genetics ; Persistent Infection/metabolism/microbiology ; Principal Component Analysis ; Pseudomonas Infections/*metabolism/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Cystic fibrosis (CF) disease leads to altered lung and gut microbiomes compared to healthy subjects. The magnitude of this dysbiosis is influenced by organ-specific microenvironmental conditions at different stages of the disease. However, how this gut-lung dysbiosis is influenced by Pseudomonas aeruginosa chronic infection is unclear. To test the relationship between CFTR dysfunction and gut-lung microbiome under chronic infection, we established a model of P. aeruginosa infection in wild-type (WT) and gut-corrected CF mice. Using 16S ribosomal RNA gene, we compared lung, stool, and gut microbiota of C57Bl/6 Cftr [tm1UNC]TgN(FABPCFTR) or WT mice at the naïve state or infected with P. aeruginosa.&amp;nbsp;P. aeruginosa infection influences murine health significantly changing body weight both in CF and WT mice. Both stool and gut microbiota revealed significantly higher values of alpha diversity in WT mice than in CF mice, while lung microbiota showed similar values. Infection with P. aeruginosa did not changed the diversity of the stool and gut microbiota, while a drop of diversity of the lung microbiota was observed compared to non-infected mice. However, the taxonomic composition of gut microbiota was shown to be influenced by P. aeruginosa infection in CF mice but not in WT mice. This finding indicates that P. aeruginosa chronic infection has a major impact on microbiota diversity and composition in the lung. In the gut, CFTR genotype and P. aeruginosa infection affected the overall diversity and taxonomic microbiota composition, respectively. Overall, our results suggest a cross-talk between lung and gut microbiota in relation to P. aeruginosa chronic infection and CFTR mutation.}, }
@article {pmid34827783, year = {2021}, author = {Xie, W and Palme, R and Schafmayer, C and Zechner, D and Vollmar, B and Grambow, E}, title = {Distress Analysis of Mice with Cervical Arteriovenous Fistulas.}, journal = {Animals : an open access journal from MDPI}, volume = {11}, number = {11}, pages = {}, pmid = {34827783}, issn = {2076-2615}, support = {FOR 2591//Deutsche Forschungsgemeinschaft/ ; }, abstract = {The welfare of laboratory animals is a consistent concern for researchers. Its evaluation not only fosters ethical responsibility and addresses legal requirements, but also provides a solid basis for a high quality of research. Recently, a new cervical arteriovenous model was created in mice to understand the pathophysiology of arteriovenous fistula, which is the most commonly used access for hemodialysis. This study evaluates the distress caused by this new animal model. Ten male C57B6/J mice with cervical arteriovenous fistula were observed for 21 days. Non-invasive parameters, such as body weight, faecal corticosterone metabolites, burrowing activity, nesting activity and distress scores were evaluated at each time point. Six out of ten created arteriovenous fistula matured within the observation time as defined by an increased diameter. The body weight of all animals was reduced after surgery but recovered within five days. In addition, the distress score was significantly increased during the early time point but not at the late time point after arteriovenous fistula creation. Neither burrowing activity nor nesting behaviour were significantly reduced after surgical intervention. Moreover, faecal corticosterone metabolite concentrations did not significantly increase. Therefore, the cervical murine arteriovenous fistula model induced moderate distress in mice and revealed an appropriate maturation rate of the fistulas.}, }
@article {pmid34826617, year = {2022}, author = {Ghani, R and Mullish, BH and Davies, FJ and Marchesi, JR}, title = {How to adapt an intestinal microbiota transplantation programme to reduce the risk of invasive multidrug-resistant infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {4}, pages = {502-512}, doi = {10.1016/j.cmi.2021.11.006}, pmid = {34826617}, issn = {1469-0691}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; MR/T005254/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19 ; *Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Vulnerable patients with intestinal colonization of multidrug-resistant organisms (MDROs) are recognized to be at increased risk of invasive MDRO-driven infection. Intestinal microbiota transplantation (IMT, also called faecal microbiota transplant) is the transfer of healthy screened donor stool to an affected recipient, and recent interest has focused on its impact on the reduction of invasive MDRO infection.<br><br>OBJECTIVES: To describe how to establish a clinical IMT pathway for patients at risk of MDRO invasive infection, with special considerations for optimizing administration and assessment of endpoints.<br><br>SOURCES: Expert guidelines and peer-reviewed clinical studies are encompassed and discussed.<br><br>CONTENT: IMT is offered to patients with MDROs detected on rectal or stool screening and either at risk of MDRO invasive infection due to altered immune status or those with recurrent MDRO-mediated invasive disease and considered at risk of further disease. Donor screening should include pathogens with theoretical or demonstrated risk of transmission (including MDROs themselves and SARS-CoV-2) and take into consideration the relative immunosuppressed state of potential recipients. Delivery of IMT is timed for when the patient is free from active infection, but no additional antibiotics are indicated. If administered when future immunosuppression is to take place, IMT is aligned at least 2&#xa0;weeks beforehand to ensure sufficient time for engraftment. Patients are followed up in terms of adverse effects from IMT and clinicians are advised to discuss with the IMT multidisciplinary team on choice of antibiotics if needed to take into consideration the impact upon the intestinal microbiome. Prevention of invasive disease is the primary measure of success, rather than using intestinal decolonization as a binary outcome. Repeat IMT is considered case by case.<br><br>IMPLICATIONS: Future research areas should include randomized studies that consider clinical outcomes and cost-effectiveness, and better understanding of mechanisms to identify markers of treatment success and functional microbiome components that could be used therapeutically.}, }
@article {pmid34818535, year = {2021}, author = {Chang, CS and Liao, YC and Huang, CT and Lin, CM and Cheung, CHY and Ruan, JW and Yu, WH and Tsai, YT and Lin, IJ and Huang, CH and Liou, JS and Chou, YH and Chien, HJ and Chuang, HL and Juan, HF and Huang, HC and Chan, HL and Liao, YC and Tang, SC and Su, YW and Tan, TH and Bäumler, AJ and Kao, CY}, title = {Identification of a gut microbiota member that ameliorates DSS-induced colitis in intestinal barrier enhanced Dusp6-deficient mice.}, journal = {Cell reports}, volume = {37}, number = {8}, pages = {110016}, doi = {10.1016/j.celrep.2021.110016}, pmid = {34818535}, issn = {2211-1247}, mesh = {Animals ; Caco-2 Cells ; Colitis/*microbiology/prevention &amp; control ; Colon/metabolism ; Dextran Sulfate/pharmacology ; Disease Models, Animal ; Dual Specificity Phosphatase 6/deficiency/genetics/*metabolism ; Dysbiosis/metabolism ; Epithelial Cells/metabolism ; Feces ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestinal Mucosa/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; RNA, Ribosomal, 16S/metabolism ; }, abstract = {Strengthening the gut epithelial barrier is a potential strategy for management of gut microbiota-associated illnesses. Here, we demonstrate that dual-specificity phosphatase 6 (Dusp6) knockout enhances baseline colon barrier integrity and ameliorates dextran sulfate sodium (DSS)-induced colonic injury. DUSP6 mutation in Caco-2 cells enhances the epithelial feature and increases mitochondrial oxygen consumption, accompanied by altered glucose metabolism and decreased glycolysis. We find that Dusp6-knockout mice are more resistant to DSS-induced dysbiosis, and the cohousing and fecal microbiota transplantation experiments show that the gut/fecal microbiota derived from Dusp6-knockout mice also confers protection against colitis. Further culturomics and mono-colonialization experiments show that one gut microbiota member in the genus Duncaniella confers host protection from DSS-induced injury. We identify Dusp6 deficiency as beneficial for shaping the gut microbiota eubiosis necessary to protect against gut barrier-related diseases.}, }
@article {pmid34815646, year = {2021}, author = {Michailidis, L and Currier, AC and Le, M and Flomenhoft, DR}, title = {Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies.}, journal = {Annals of gastroenterology}, volume = {34}, number = {6}, pages = {802-814}, pmid = {34815646}, issn = {1108-7471}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has shown excellent efficacy in treating Clostridioides difficile infection, as well as promise in several other diseases. The heightened interest is accompanied by concerns over adverse events (AE) and safety. To further understand that in FMT, we performed a systematic review of the literature and a meta-analysis of high-quality, prospective randomized controlled trials FMT.<br><br>METHODS: Studies were selected based on predefined exclusion criteria and were assessed for quality. Only prospective, randomized, controlled studies of high quality were included in the final analysis. Data were extracted on demographics, AE, indication, delivery method and follow-up duration.<br><br>RESULTS: Out of 334 articles reviewed, 9 high quality studies with 756 FMTs were selected for final analysis. The pooled rate of AE was 39.3% (95% confidence interval [CI] 0.19-0.642) as they were reported by 112 patients who received FMT. The SAE rate was 5.3% (95%CI 3.1-8.8%). The most common AE reported was abdominal pain, followed by diarrhea. The most common SAE was Clostridium difficile infection. Upper gastrointestinal tract delivery was associated with a higher rate of total AE, but not SAE.<br><br>CONCLUSIONS: Based on the selected studies, the AE rate of FMT is 39.3%, with most AE being mild and self-limiting. SAE were uncommon at 5.3%, and many were only possibly related to the FMT. Adherence to standardized reporting of AE as well as longitudinal studies and registries will help further clarify the safety of FMT in the future.}, }
@article {pmid34813937, year = {2021}, author = {Ma, Y and Guo, R and Sun, Y and Li, X and He, L and Li, Z and Silverman, GJ and Chen, G and Gao, F and Yuan, J and Wei, Q and Li, M and Lu, L and Niu, H}, title = {Lupus gut microbiota transplants cause autoimmunity and inflammation.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {233}, number = {}, pages = {108892}, doi = {10.1016/j.clim.2021.108892}, pmid = {34813937}, issn = {1521-7035}, support = {P50 AR070591/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Autoimmunity/*immunology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Germ-Free Life ; Histidine/metabolism ; Humans ; Inflammation/*immunology ; Lupus Erythematosus, Systemic/*microbiology ; Mice ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16 s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free (GF) mice.<br><br>RESULTS: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to GF mice caused GF mice to develop a series of lupus-like phenotypic features, including increased serum autoimmune antibodies, imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants.<br><br>CONCLUSIONS: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.}, }
@article {pmid34812117, year = {2021}, author = {Zhilu, X and Xiangqian, D and Keli, Y and Caroline, C and Jingwan, Z and Yu, L and Tao, Z and Cheung, CL and Yang, S and Fengrui, Z and Kl, CF and Jy, SJ and Jun, Y and Anthony, B and Nicolas, B and Jean-Frédéric, C and Sunny Hei, W and Yinglei, M and Siew C, N}, title = {Association of Adherent-invasive Escherichia coli with severe Gut Mucosal dysbiosis in Hong Kong Chinese population with Crohn's disease.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1994833}, pmid = {34812117}, issn = {1949-0984}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Aged ; Animals ; Asian People ; Bacterial Adhesion ; Crohn Disease/epidemiology/*microbiology/therapy ; Dysbiosis/epidemiology/*microbiology/therapy ; Escherichia coli/isolation &amp; purification/*pathogenicity ; Escherichia coli Infections/epidemiology/*microbiology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Hong Kong/epidemiology ; Humans ; Ileum/microbiology ; Intestinal Mucosa/*microbiology ; Male ; Mice ; Middle Aged ; Prevalence ; }, abstract = {Adherent invasive Escherichia Coli (AIEC) has been implicated in the pathogenesis of Crohn's disease (CD) in Western populations. Whether the presence of AIEC is also seen in CD populations of different genetic susceptibility and has negative impact on host microbiota ecology and therapeutics are unclear. AIEC presence was assessed in ileal tissues of 60 Hong Kong Chinese patients with CD and 56 healthy subjects. Mucosa microbiota was analyzed by 16s rRNA sequencing. Impact of AIEC on the gut microbiota was determined in a mouse model. AIEC was significantly more prevalent in ileal tissues of patients with CD than controls (30% vs 7.1%). Presence of AIEC in ileal tissues was associated with more severe mucosa microbiota dysbiosis in CD with decreased diversity and lower abundance of Firmicutes including butyrate producing Roseburia and probiotic Bacillus. A random forest model predicted the presence of AIEC with area under the curve of 0.89. AIEC exacerbated dysbiosis in dextran sodium sulfate (DSS)-induced colitis mice and led to resistance to restoration of normal gut microbiota by fecal microbiota transplantation (FMT). Proportion of donor-derived bacteria in AIEC-colonized mice was significantly lower than that in uninfected mice. AIEC was prevalent and associated with severe mucosa microbiota dysbiosis in CD in Hong Kong Chinese population. The presence of AIEC impeded restoration of normal gut microbiota. AIEC may serve as a keystone bacterium in CD and impact the efficacy of FMT.}, }
@article {pmid34808360, year = {2022}, author = {Kang, K and Zhou, Q and McGinn, L and Nguyen, T and Luo, Y and Djalilian, A and Rosenblatt, M}, title = {High fat diet induced gut dysbiosis alters corneal epithelial injury response in mice.}, journal = {The ocular surface}, volume = {23}, number = {}, pages = {49-59}, pmid = {34808360}, issn = {1937-5913}, support = {K12 EY021475/EY/NEI NIH HHS/United States ; P30 EY001792/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Corneal Injuries ; *Diet, High-Fat/adverse effects ; Dysbiosis ; Female ; Inflammation ; Mice ; Mice, Inbred C57BL ; }, abstract = {PURPOSE: Commensal microbiome secretes various metabolites that can exert important effects on the host immunity and inflammation and can alter cellular functions. However, little is known regarding the effect of microbiome on corneal immunity and genetic expression. The purpose of this study is to describe the effect of diet-induced gut dysbiosis on corneal immunity and corneal gene expression after wounding.<br><br>METHODS: This study is approved by the Animal Care and Use of the University of Illinois. Six-week-old female C57BL6 mice were fed on a normal chow diet (ND), isocaloric low-fat control diet (LFD), or a 21% milk high-fat diet (HFD) for six weeks. 2&#xa0;mm corneal epithelial debridement was performed (n&#xa0;=&#xa0;10). Fecal samples from mice were used for microbial diversity analysis (n&#xa0;>&#xa0;3). Immunofluorescence staining of corneal wholemount tissue post-debridement was used to visualize immune cell distribution. RNA Seq was performed on tissue samples from corneas following debridement.<br><br>RESULTS: Mice fed differing diets had significant alterations in gut microbial diversities. After corneal debridement, HFD mice experienced delayed wound healing in comparison to LFD mice and ND mice groups. However, fecal transplantation led to normalization of wound closure rates. Increased &#x3b3;&#x3b4;TCR staining was observed in the LFD group, and decreased LY6G was observed in HFD group (p&#xa0;<&#xa0;0.05). Gene Ontology terms of differentially expressed genes included response to external stimulus, cell proliferation, migration, adhesion, defense response and leukocyte migration. Top over-represented pathways included ECM-receptor interaction, Cytokine-cytokine receptor interaction, Focal adhesion and Leukocyte trans-endothelial migration.<br><br>CONCLUSIONS: Gut microbial dysbiosis alters corneal immune cell distribution, corneal response to injury, and genes related to epithelial function and corneal immunity.}, }
@article {pmid34807442, year = {2022}, author = {Mu, C and Pi, Y and Zhang, C and Zhu, W}, title = {Microbiomes in the Intestine of Developing Pigs: Implications for Nutrition and Health.}, journal = {Advances in experimental medicine and biology}, volume = {1354}, number = {}, pages = {161-176}, pmid = {34807442}, issn = {0065-2598}, mesh = {Animals ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Intestines ; *Microbiota ; Swine ; }, abstract = {The past decade has seen an expansion of studies on the role of gut microbiome in piglet nutrition and health. With the help of culture-independent sequencing techniques, the colonization of gut microbiota and their implication in physiology are being investigated in depth. Immediately after birth, the microbes begin to colonize following an age-dependent trajectory, which can be modified by maternal environment, diet, antibiotics, and fecal microbiota transplantation. The early-life gut microbiome is relatively simple but enriched with huge metabolic potential to utilize milk oligosaccharides and affect the epithelial function. After weaning, the gut microbiome develops towards a gradual adaptation to the introduction of solid food, with an enhanced ability to metabolize amino acids, fibers, and bile acids. Here we summarize the compositional and functional difference of the gut microbiome in the keystone developing phases, with a specific focus on the use of different nutritional approaches based on the phase-specific gut microbiome.}, }
@article {pmid34805249, year = {2021}, author = {Yang, J and Xiong, P and Bai, L and Zhang, Z and Zhou, Y and Chen, C and Xie, Z and Xu, Y and Chen, M and Wang, H and Zhu, M and Yu, J and Wang, K}, title = {The Association of Altered Gut Microbiota and Intestinal Mucosal Barrier Integrity in Mice With Heroin Dependence.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {765414}, pmid = {34805249}, issn = {2296-861X}, abstract = {The gut microbiota is believed to play a significant role in psychological and gastrointestinal symptoms in heroin addicts. However, the underlying mechanism remains largely unknown. We show here that heroin addicts had a decrease in body mass index (BMI) and abnormal serum D-lactic acid (DLA), endotoxin (ET) and diamine oxidase (DAO) levels during their withdrawal stage, suggesting a potential intestinal injury. The gut microbial profiles in the mouse model with heroin dependence showed slightly decreased alpha diversity, as well as higher levels of Bifidobacterium and Sutterella and a decrease in Akkermansia at genus level compared to the control group. Fecal microbiota transplantation (FMT) further confirmed that the microbiota altered by heroin dependence was sufficient to impair body weight and intestinal mucosal barrier integrity in recipient mice. Moreover, short-chain fatty acids (SCFAs) profiling revealed that microbiota-derived propionic acid significantly decreased in heroin dependent mice compared to controls. Overall, our study shows that heroin dependence significantly altered gut microbiota and impaired intestinal mucosal barrier integrity in mice, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.}, }
@article {pmid34804275, year = {2021}, author = {Hazan, S and Dave, S and Papoutsis, AJ and Barrows, BD and Borody, TJ}, title = {Successful Bacterial Engraftment Identified by Next-Generation Sequencing Predicts Success of Fecal Microbiota Transplant for Clostridioides difficile.}, journal = {Gastroenterology research}, volume = {14}, number = {5}, pages = {304-309}, pmid = {34804275}, issn = {1918-2805}, abstract = {BACKGROUND: The effectiveness of fecal microbiota transplantation (FMT), a treatment for Clostridioides difficile infection (CDI), is dependent on successful engraftment (incorporation) of donor stool. We present a method for evaluating engraftment success based on next-generation sequencing (NGS)-based profiling of bacterial strains present in donor and recipient stool, and we suggest its potential to guide treatment decisions.<br><br>METHODS: Bacterial strains in stool samples from three patients from the clinic and one donor were analyzed via NGS and metagenomic sequencing, before and 1 month after FMT for CDI. The similarity of strains present was assessed via relative abundance, principal component analysis, Shannon and Simpson diversity indexes, and Bray-Curtis dissimilarity matrix. A positive outcome was successful engraftment, where the post-FMT sample closely resembled that of the donor and CDI was cured.<br><br>RESULTS: Patients (Pts.) 1 and 2, but not Pt. 3's stool samples closely resembled the donor specimen post-FMT. Noteworthy, Pt. 3 pre-FMT sample was less similar to the donor than that of Pts. 1 and 2. All methods of assessing similarity and dissimilarity used yielded virtually identical conclusions. Pts. 1 and 2 which closely resembled donor specimen, eradicated CDI giving a surrogate objective measure of engraftment.<br><br>CONCLUSIONS: Success of engraftment in FMT can be assessed using NGS and metagenomic analysis and parallels success in curing CDI of the microbiome. The statistical methods we present here are reliable and consistent for such purposes. The dissimilarity of Pt. 3 to the donor combined with the failure of engraftment and failure to cure CDI in Pt. 3 suggests that FMT success may be predictable by comparing pre-FMT samples to donor. There is no clinical trial registry listing this study.}, }
@article {pmid34804005, year = {2021}, author = {Sun, Y and Xie, R and Li, L and Jin, G and Zhou, B and Huang, H and Li, M and Yang, Y and Liu, X and Cao, X and Wang, B and Liu, W and Jiang, K and Cao, H}, title = {Prenatal Maternal Stress Exacerbates Experimental Colitis of Offspring in Adulthood.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {700995}, pmid = {34804005}, issn = {1664-3224}, mesh = {Animals ; Caco-2 Cells ; Colitis/chemically induced/*microbiology/therapy ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; In Situ Hybridization, Fluorescence ; Inflammation/pathology ; Intestinal Mucosa/*pathology ; Mice ; Mice, Inbred C57BL ; Pregnancy ; Prenatal Exposure Delayed Effects/*physiopathology ; Stress, Psychological/*physiopathology ; }, abstract = {The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.}, }
@article {pmid34803700, year = {2021}, author = {Wang, Y and Zhang, J and Xu, L and Ma, J and Lu, M and Ma, J and Liu, Z and Wang, F and Tang, X}, title = {Modified Gegen Qinlian Decoction Regulates Treg/Th17 Balance to Ameliorate DSS-Induced Acute Experimental Colitis in Mice by Altering the Gut Microbiota.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {756978}, pmid = {34803700}, issn = {1663-9812}, abstract = {Inflammatory bowel disease (IBD) is characterized by chronic pathology associated with extensive intestinal microbial dysregulation and intestinal inflammation. Thus, efforts are underway to manipulate the gut microbiome to improve inflammatory pathology. Gegen Qinlian decoction (GQD), a traditional Chinese medicine prescription, has been widely utilized for treating diarrhea and ulcerative colitis (UC) for thousands of years. However, the underlying mechanism of its efficacy and whether its protective effect against colitis is mediated by the gut microbiota are poorly understood. In the present study, our data demonstrated that modified GQD (MGQD) administration significantly improved the pathological phenotypes and colonic inflammation challenged by DSS in mice, which were specifically manifested as reduced loss of body weight, shortening of colon length, DAI score, histological score and suppressed inflammatory response. 16S rRNA sequencing and targeted metabonomics analysis showed that MQGD altered the diversity and community landscape of the intestinal microbiota and the metabolic profiles. In particular, MQGD significantly boosted the abundance of the intestinal microbiota producing short-chain fatty acids (SCFAs), which are causally associated with promoting the development of Treg cells and suppressing the differentiation of pro-inflammatory Th17 cells. More importantly, transferring fecal microbiota from MGQD-treated or healthy controls exhibited equivalent alleviative effects on colitis mice. However, this protective effect could not be replicated in experiments of mice with depleted intestinal microbes through broad-spectrum antibiotic cocktails (ABX), further supporting the importance of SCFA-producing gut microbiota in the beneficial role of MGQD. In general, MGQD therapy has the potential to remodel the intestinal microbiome and reestablish immune homeostasis to ameliorate DSS-induced colitis.}, }
@article {pmid34803517, year = {2021}, author = {Amedei, A and Capasso, C and Nannini, G and Supuran, CT}, title = {Microbiota, Bacterial Carbonic Anhydrases, and Modulators of Their Activity: Links to Human Diseases?.}, journal = {Mediators of inflammation}, volume = {2021}, number = {}, pages = {6926082}, pmid = {34803517}, issn = {1466-1861}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/*enzymology ; Carbonic Anhydrase Inhibitors/pharmacology ; Carbonic Anhydrases/*physiology ; Dysbiosis/etiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Prebiotics ; Probiotics/pharmacology ; Synbiotics ; }, abstract = {The involvement of the human microbiome is crucial for different host functions such as protection, metabolism, reproduction, and especially immunity. However, both endogenous and exogenous factors can affect the balance of the microbiota, creating a state of dysbiosis, which can start various gastrointestinal or systemic diseases. The challenge of future medicine is to remodel the intestinal microbiota to bring it back to healthy equilibrium (eubiosis) and, thus, counteract its negative role in the diseases' onset. The shaping of the microbiota is currently practiced in different ways ranging from diet (or use of prebiotics, probiotics, and synbiotics) to phage therapy and antibiotics, including microbiota fecal transplantation. Furthermore, because microbiota modulation is a capillary process, and because many microbiota bacteria (both beneficial and pathogenic) have carbonic anhydrases (specifically the four classes α, β, γ, and ι), we believe that the use of CA inhibitors and activators can open up new therapeutic strategies for many diseases associated with microbial dysbiosis, such as the various gastrointestinal disorders and the same colorectal cancer.}, }
@article {pmid34801681, year = {2022}, author = {Huang, S and Hu, S and Liu, S and Tang, B and Liu, Y and Tang, L and Lei, Y and Zhong, L and Yang, S and He, S}, title = {Lithium carbonate alleviates colon inflammation through modulating gut microbiota and Treg cells in a GPR43-dependent manner.}, journal = {Pharmacological research}, volume = {175}, number = {}, pages = {105992}, doi = {10.1016/j.phrs.2021.105992}, pmid = {34801681}, issn = {1096-1186}, mesh = {Adult ; Aged ; Animals ; Anti-Inflammatory Agents/pharmacology/*therapeutic use ; Colitis/chemically induced/*drug therapy/immunology/microbiology ; Dextran Sulfate ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Humans ; Lithium Carbonate/pharmacology/*therapeutic use ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Receptors, G-Protein-Coupled/*genetics ; T-Lymphocytes, Regulatory/*drug effects/immunology ; Mice ; }, abstract = {BACKGROUND: Recent evidence suggests that neuropsychiatric stabilizers have a place in resolving gastrointestinal disorders. Lithium carbonate (LC) is one of the most commonly used drugs for bipolar disorder clinically. Here, we estimate the therapeutic function of LC against colitis and investigate the mechanism of intestinal flora and metabolism modulation.<br><br>METHODS: A colitis model was constructed by continuously administering 2.5% dextran sodium sulfate (DSS) solution daily for 7 days. Analysis of gut microbiota was carried out by 16S rRNA gene high-throughput sequencing. Spectrum antibiotic cocktail (ABX) and faecal microbiota transplantation (FMT) were employed to evaluate the protective effect of intestinal flora. Colonic Treg cells and related immune responses were detected by flow cytometry.<br><br>RESULTS: LC treatment significantly alleviated colon inflammation by regulating gut microbial diversity and altering flora composition. Notably, LC treatment upregulated short-chain fatty acid (SCFA)-producing bacteria, especially Akkermansia muciniphila (A. muciniphila), and transformed metabolite SCFA profiles. LC activated anti-inflammatory Treg cell responses in colonic lamina propria (LP) in a G-protein coupled receptor 43 (GPR43)-dependent mechanism. ABX, FMT and single bacteria gavage experiments were conducted to confirm the above mechanism.<br><br>CONCLUSIONS: As an intestinal microbiome and metabolite modulator, LC alleviates colon inflammation in a GPR43-dependent manner through activating Treg cell responses. Therefore, the therapeutic strategy of the microbiome-metabolite-immune axis, as observed in the A. muciniphila-SCFA-Treg cell axis in our study, might provide a new direction for the treatment of IBD.}, }
@article {pmid34801513, year = {2022}, author = {Kozlova, EV and Carabelli, B and Bishay, AE and Liu, R and Denys, ME and Macbeth, JC and Piamthai, V and Crawford, MS and McCole, DF and Zur Nieden, NI and Hsiao, A and Curras-Collazo, MC}, title = {Induction of distinct neuroinflammatory markers and gut dysbiosis by differential pyridostigmine bromide dosing in a chronic mouse model of GWI showing persistent exercise fatigue and cognitive impairment.}, journal = {Life sciences}, volume = {288}, number = {}, pages = {120153}, pmid = {34801513}, issn = {1879-0631}, support = {R01 AI157106/AI/NIAID NIH HHS/United States ; R35 GM124724/GM/NIGMS NIH HHS/United States ; R01 DK130373/DK/NIDDK NIH HHS/United States ; R01 DK091281/DK/NIDDK NIH HHS/United States ; R21 AI152017/AI/NIAID NIH HHS/United States ; R01 AI153314/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Biomarkers/analysis ; Cholinesterase Inhibitors/administration &amp; dosage/toxicity ; Cognitive Dysfunction/etiology/metabolism/*pathology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Dysbiosis/etiology/metabolism/*pathology ; Endotoxemia/etiology/metabolism/pathology ; Fatigue/etiology/metabolism/*pathology ; *Gastrointestinal Microbiome ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Gliosis/etiology/metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Neuralgia/etiology/metabolism/pathology ; Neuroinflammatory Diseases/etiology/metabolism/*pathology ; Persian Gulf Syndrome/*drug therapy ; *Physical Conditioning, Animal ; Pyridostigmine Bromide/administration &amp; dosage/*toxicity ; }, abstract = {AIMS: To characterize neuroinflammatory and gut dysbiosis signatures that accompany exaggerated exercise fatigue and cognitive/mood deficits in a mouse model of Gulf War Illness (GWI).<br><br>METHODS: Adult male C57Bl/6N mice were exposed for 28 d (5&#xa0;d/wk) to pyridostigmine bromide (P.O.) at 6.5&#xa0;mg/kg/d, b.i.d. (GW1) or 8.7&#xa0;mg/kg/d, q.d. (GW2); topical permethrin (1.3&#xa0;mg/kg), topical N,N-diethyl-meta-toluamide (33%) and restraint stress (5&#xa0;min). Animals were phenotypically evaluated as described in an accompanying article [124] and sacrificed at 6.6&#xa0;months post-treatment (PT) to allow measurement of brain neuroinflammation/neuropathic pain gene expression, hippocampal glial fibrillary acidic protein, brain Interleukin-6, gut dysbiosis and serum endotoxin.<br><br>KEY FINDINGS: Compared to GW1, GW2 showed a more intense neuroinflammatory transcriptional signature relative to sham stress controls. Interleukin-6 was elevated in GW2 and astrogliosis in hippocampal CA1 was seen in both GW groups. Beta-diversity PCoA using weighted Unifrac revealed that gut microbial communities changed after exposure to GW2 at PT188. Both GW1 and GW2 displayed systemic endotoxemia, suggesting a gut-brain mechanism underlies the neuropathological signatures. Using germ-free mice, probiotic supplementation with Lactobacillus reuteri produced less gut permeability than microbiota transplantation using GW2 feces.<br><br>SIGNIFICANCE: Our findings demonstrate that GW agents dose-dependently induce differential neuropathology and gut dysbiosis associated with cognitive, exercise fatigue and mood GWI phenotypes. Establishment of a comprehensive animal model that recapitulates multiple GWI symptom domains and neuroinflammation has significant implications for uncovering pathophysiology, improving diagnosis and treatment for GWI.}, }
@article {pmid34801432, year = {2022}, author = {Ciftciler, R and Ciftciler, AE}, title = {The importance of microbiota in hematology.}, journal = {Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis}, volume = {61}, number = {2}, pages = {103320}, doi = {10.1016/j.transci.2021.103320}, pmid = {34801432}, issn = {1473-0502}, mesh = {Dysbiosis/therapy ; *Gastrointestinal Microbiome ; *Hematology ; Humans ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {Whilst particular infectious bacteria are well-established to be associated with hematological diseases, more recent interest has focused on the entire microbial community of mucosal surfaces. In particular, the link between hematology and the microbiota (defined as the total assemblage of microorganisms in a mucosal environment)/ microbiome (i.e. the entire ecological habitat, including organisms, their genomes and environmental conditions) is becoming more well-known. Dysbiosis, or a change in the microbiome, has been linked to the development of neoplasms, infections, inflammatory illnesses, and immune-mediated disorders, according to growing data. Microbiota may influence distant tumor microenvironment through a variety of methods, including cytokine release control, dendritic cell activation, and T-cell lymphocyte stimulation. There are numerous major implications to study the microbiome in patients with benign and malignant hematologic disorders. In this review, we investigated the structure and function of the microbiome in patients with benign and malignant hematological diseases. Chemotherapy and immunosuppressive agents used in treatment of these benign and malignant hematological diseases may cause or exacerbate dysbiosis and infectious problems. After understanding the importance of microbiota in hematological diseases, we think that use of probiotics and dietary prebiotic substances targeting microbiota modification aiming to improve hematological disease outcomes should be investigated in future studies.}, }
@article {pmid34800683, year = {2022}, author = {Kang, Y and Kang, X and Cai, Y}, title = {The gut microbiome as a target for adjuvant therapy in insomnia disorder.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {46}, number = {1}, pages = {101834}, doi = {10.1016/j.clinre.2021.101834}, pmid = {34800683}, issn = {2210-741X}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Probiotics/therapeutic use ; Quality of Life ; *Sleep Initiation and Maintenance Disorders/therapy ; }, abstract = {Insomnia is a type of sleep disorder which has negative impacts on the quality of life, mood, cognitive function and health of humans. The etiology of insomnia may be related to many factors such as genetics, biochemistry, neuroendocrine, immune, and psychosocial factors. However, the detailed pathological aspects of insomnia remain unclear. Recent investigation of the microbiome-gut-brain axis enhances our understanding of the role of the gut microbiota in brain-related diseases. Gut microbiome has been shown to be associated with insomnia. However, the available data in this field remain limited and the relevant scientific work has only recently begun. This review aims to summarize the recent literature as an aid to better understanding how the alteration of gut microbiota composition contributes to insomnia while evaluating and prospecting the therapeutic effect of modulating gut microbiota in the treatment of insomnia based on previous publications.}, }
@article {pmid34799288, year = {2022}, author = {Mégier, C and Bourbao-Tournois, C and Perrotin, F and Merle, P and Ouaissi, M and Diguisto, C}, title = {Long-term evaluation of the impact of delivery modalities on anal continence in women with Crohn's disease.}, journal = {Journal of visceral surgery}, volume = {159}, number = {5}, pages = {353-361}, doi = {10.1016/j.jviscsurg.2021.08.002}, pmid = {34799288}, issn = {1878-7886}, mesh = {Anal Canal ; Cesarean Section/adverse effects ; *Crohn Disease/complications ; *Fecal Incontinence/etiology ; Female ; Humans ; Pregnancy ; Retrospective Studies ; }, abstract = {CONTEXT: Crohn's disease (CD) and sphincter injury during childbirth are two risk factors for anal incontinence (AI). The long-term risk of developing AI in women with CD after childbirth has never been studied.<br><br>GOAL: The main objective of the study is to assess the risk of developing severe AI after childbirth in women with CD.<br><br>METHODS: A retrospective study was performed in women with CD who gave birth in a French "Level 3" maternity hospital between 2000 and 2015. The primary endpoint was severe AI as defined by a Wexner score&#x2265;9 or a St. Mark's score&#x2265;9, at least five years after childbirth. The association between delivery route and occurrence of severe AI was assessed by univariate and multivariate analyses.<br><br>RESULTS: Forty-six women were included, 32 of whom were delivered vaginally and 14 by Caesarean section. Thirty-one percent of the women had severe AI according to the Wexner score, and 41% according to the St. Mark's score. Two factors were associated with severe AI: vaginal delivery and the occurrence of an obstetric perineal injury: (crude OR=8.89, 95% (CI: 1.03-76.57) and crude OR=4.16, 95% (CI: 1.06-16.27) respectively for AI defined by the Wexner score, and crude OR=6.8, 95% (CI: 1.30-35.41) and crude OR=4.3, 95% (CI: 1.23-15.2) for AI defined by the St. Mark's score). After adjusting for confounding factors, only vaginal delivery was associated with severe AI (adjusted OR=22.86, 95% CI: 1.52-931.28 for a Wexner score&#x2265;9 and adjusted OR=16. 11 (95% CI: 1.43-533.26) for a St Mark score&#x2265;9).<br><br>CONCLUSION: Vaginal birth was associated with the development of severe long-term AI in women with CD.}, }
@article {pmid34797954, year = {2022}, author = {Cheng, J and Li, W and Wang, Y and Cao, Q and Ni, Y and Zhang, W and Guo, J and Chen, B and Zang, Y and Zhu, Y}, title = {Electroacupuncture modulates the intestinal microecology to improve intestinal motility in spinal cord injury rats.}, journal = {Microbial biotechnology}, volume = {15}, number = {3}, pages = {862-873}, pmid = {34797954}, issn = {1751-7915}, mesh = {Animals ; *Electroacupuncture ; Fecal Microbiota Transplantation ; Gastrointestinal Motility ; Rats ; Serotonin ; *Spinal Cord Injuries/metabolism/pathology/therapy ; }, abstract = {Spinal cord injury (SCI) is a disease involving gastrointestinal disorders. The underlying mechanisms of the potential protective effects of electroacupuncture (EA) and 5-hydroxytryptamine (5-HT) system on SCI remain unknown. We investigated whether EA improves gut microbial dysbiosis in SCI and regulates the 5-HT system. 16S rDNA gene sequencing was applied to investigate alterations in the gut microbiome of the rats. Faecal metabolites and the expression of the 5-HT system were detected. EA and faecal microbiota transplantation (FMT) treatment facilitated intestinal transmission functional recovery and restored the colon morphology of SCI rats. The composition of the intestinal microbiota, including numbers of phylum Proteobacteria, class Clostridia, order Bacteroidales, and genus Dorea, were amplified in SCI rats, and EA and FMT significantly reshaped the intestinal microbiota. SCI resulted in disturbed metabolic conditions in rats, and the EA and FMT group showed increased amounts of catechin compared with SCI rats. SCI inhibited 5-HT system expression in the colon, which was significantly reversed by EA and FMT treatment. Therefore, EA may ameliorate SCI by modulating microbiota and metabolites and regulate the 5-HT system. Our study provides new insights into the pathogenesis and therapy of SCI from the perspective of microbiota and 5-HT regulation.}, }
@article {pmid34795654, year = {2021}, author = {Han, T and Hu, X and Li, K and Zhang, D and Zhang, Y and Li, J}, title = {Bifidobacterium infantis Maintains Genome Stability in Ulcerative Colitis via Regulating Anaphase-Promoting Complex Subunit 7.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {761113}, pmid = {34795654}, issn = {1664-302X}, abstract = {Probiotics represents a promising intestinal microbiota-targeted therapeutic method for the treatment of ulcerative colitis (UC). Several lines of evidence implicate that Bifidobacterium infantis serves as a probiotic strain with proven efficacy in maintaining the remission of UC. However, the exact mechanisms underlying the beneficial effects of B. infantis on UC progression have yet to be elucidated. Herein, we provide evidence that B. infantis acts as a key predisposing factor for the maintenance of host genome stability. First, we showed that the fecal microbiota transplantation (FMT) of UC-derived feces contributes to more severely DNA damage in dextran sodium sulfate (DSS)-induced mice likely due to mucosa-associated microbiota alterations, as reflected by the rapid appearance of DNA double strand breaks (DSBs), a typical marker of genome instability. Genomic DNA damage analysis of colon tissues derived from healthy controls, patients with UC or dysplasia, and colitis associated cancer (CAC) patients, revealed an enhanced level of DSBs with aggravation in the degree of the intestinal mucosal lesions. To evaluate whether B. infantis modulates the host genome stability, we employed the DSS-induced colitis model and a TNFα-induced intestinal epithelial cell model. Following the administration of C57BL/6 mice with B. infantis via oral gavage, we found that the development of DSS-induced colitis in mice was significantly alleviated, in contrast to the colitis model group. Notably, B. infantis administration decreased DSB levels in both DSS-induced colitis and TNF-treated colonial cell model. Accordingly, our bioinformatic and functional studies demonstrated that B. infantis altered signal pathways involved in ubiquitin-mediated proteolysis, transcriptional misregulation in cancer, and the bacterial invasion of epithelial cells. Mechanistically, B. infantis upregulated anaphase-promoting complex subunit 7 (APC7), which was significantly suppressed in colitis condition, to activate the DNA repair pathway and alter the genome stability, while downregulation of APC7 abolished the efficiency of B. infantis treatment to induce a decrease in the level of DSBs in TNFα-induced colonial cells. Collectively, our results support that B. infantis orchestrates a molecular network involving in APC7 and genome stability, to control UC development at the clinical, biological, and mechanistic levels. Supplying B. infantis and targeting its associated pathway will yield valuable insight into the clinical management of UC patients.}, }
@article {pmid34795283, year = {2021}, author = {Vandeputte, D and De Commer, L and Tito, RY and Kathagen, G and Sabino, J and Vermeire, S and Faust, K and Raes, J}, title = {Temporal variability in quantitative human gut microbiome profiles and implications for clinical research.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {6740}, pmid = {34795283}, issn = {2041-1723}, mesh = {Adult ; Bacteria/classification/*genetics ; Belgium ; Diet ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Genetic Variation ; Humans ; Middle Aged ; Population Dynamics ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; Species Specificity ; Time Factors ; }, abstract = {While clinical gut microbiota research is ever-expanding, extending reference knowledge of healthy between- and within-subject gut microbiota variation and its drivers remains essential; in particular, temporal variability is under-explored, and a comparison with cross-sectional variation is missing. Here, we perform daily quantitative microbiome profiling on 713 fecal samples from 20 Belgian women over six weeks, combined with extensive anthropometric measurements, blood panels, dietary data, and stool characteristics. We show substantial temporal variation for most major gut genera; we find that for 78% of microbial genera, day-to-day absolute abundance variation is substantially larger within than between individuals, with up to 100-fold shifts over the study period. Diversity, and especially evenness indicators also fluctuate substantially. Relative abundance profiles show similar but less pronounced temporal variation. Stool moisture, and to a lesser extent diet, are the only significant host covariates of temporal microbiota variation, while menstrual cycle parameters did not show significant effects. We find that the dysbiotic Bact2 enterotype shows increased between- and within-subject compositional variability. Our results suggest that to increase diagnostic as well as target discovery power, studies could adopt a repeated measurement design and/or focus analysis on community-wide microbiome descriptors and indices.}, }
@article {pmid34791396, year = {2021}, author = {Bernard, R and Hourigan, SK and Nicholson, MR}, title = {Fecal Microbiota Transplantation and Microbial Therapeutics for the Treatment of Clostridioides difficile Infection in Pediatric Patients.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {10}, number = {Supplement_3}, pages = {S58-S63}, pmid = {34791396}, issn = {2048-7207}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; K23 HD099240/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Child ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and has high rates of recurrent disease. As a disease associated with intestinal dysbiosis, gastrointestinal microbiome manipulation and fecal microbiota transplantation (FMT) have evolved as effective, although relatively unregulated therapeutics and not without safety concerns. FMT for the treatment of CDI has been well studied in adults with increasing data reported in children. In this review, we discuss the current body of literature on the use of FMT in children including effectiveness, safety, risk factors for a failed FMT, and the role of FMT in children with comorbidities. We also review emerging microbial therapeutics for the treatment of rCDI.}, }
@article {pmid34788420, year = {2022}, author = {Nicholson, MR and Alexander, E and Ballal, S and Davidovics, Z and Docktor, M and Dole, M and Gisser, JM and Goyal, A and Hourigan, SK and Jensen, MK and Kaplan, JL and Kellermayer, R and Kelsen, JR and Kennedy, MA and Khanna, S and Knackstedt, ED and Lentine, J and Lewis, JD and Michail, S and Mitchell, PD and Oliva-Hemker, M and Patton, T and Queliza, K and Sidhu, S and Solomon, AB and Suskind, DL and Weatherly, M and Werlin, S and de Zoeten, EF and Kahn, SA and , }, title = {Efficacy and Outcomes of Faecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease.}, journal = {Journal of Crohn's &amp; colitis}, volume = {16}, number = {5}, pages = {768-777}, pmid = {34788420}, issn = {1876-4479}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; K23 HD099240/HD/NICHD NIH HHS/United States ; UL1 TR000445/TR/NCATS NIH HHS/United States ; 1K23AI156132-01//National Institute of Allergy and Infectious Diseases/ ; K23HD099240//National Institute of Child Health and Human Development/ ; /NH/NIH HHS/United States ; UL1 TR000445/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Child ; Chronic Disease ; *Clostridioides difficile ; *Clostridium Infections/complications/therapy ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; *Inflammatory Bowel Diseases/complications/therapy ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD.<br><br>METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained.<br><br>RESULTS: A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up.<br><br>CONCLUSIONS: Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.}, }
@article {pmid34785679, year = {2021}, author = {Giobbe, GG and Bonfante, F and Jones, BC and Gagliano, O and Luni, C and Zambaiti, E and Perin, S and Laterza, C and Busslinger, G and Stuart, H and Pagliari, M and Bortolami, A and Mazzetto, E and Manfredi, A and Colantuono, C and Di Filippo, L and Pellegata, AF and Panzarin, V and Thapar, N and Li, VSW and Eaton, S and Cacchiarelli, D and Clevers, H and Elvassore, N and De Coppi, P}, title = {SARS-CoV-2 infection and replication in human gastric organoids.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {6610}, pmid = {34785679}, issn = {2041-1723}, support = {MR/R006237/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aborted Fetus ; Aged ; Animals ; COVID-19/*pathology/virology ; Cell Line ; Child ; Child, Preschool ; Chlorocebus aethiops ; Humans ; Infant ; Intestinal Mucosa/pathology/*virology ; Middle Aged ; Organoids/pathology/*virology ; SARS-CoV-2/isolation &amp; purification/*physiology ; Stomach/pathology/*virology ; Virus Replication/*physiology ; }, abstract = {COVID-19 typically manifests as a respiratory illness, but several clinical reports have described gastrointestinal symptoms. This is particularly true in children in whom gastrointestinal symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. These observations raise the question of whether the virus can replicate within the stomach. Here we generate gastric organoids from fetal, pediatric, and adult biopsies as in vitro models of SARS-CoV-2 infection. To facilitate infection, we induce reverse polarity in the gastric organoids. We find that the pediatric and late fetal gastric organoids are susceptible to infection with SARS-CoV-2, while viral replication is significantly lower in undifferentiated organoids of early fetal and adult origin. We demonstrate that adult gastric organoids are more susceptible to infection following differentiation. We perform transcriptomic analysis to reveal a moderate innate antiviral response and a lack of differentially expressed genes belonging to the interferon family. Collectively, we show that the virus can efficiently infect the gastric epithelium, suggesting that the stomach might have an active role in fecal-oral SARS-CoV-2 transmission.}, }
@article {pmid34784980, year = {2021}, author = {Zhao, Z and Ning, J and Bao, XQ and Shang, M and Ma, J and Li, G and Zhang, D}, title = {Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {226}, pmid = {34784980}, issn = {2049-2618}, mesh = {Animals ; Brain-Gut Axis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Inflammation/chemically induced ; Lipopolysaccharides/toxicity ; Mice ; Mice, Inbred C57BL ; *Parkinson Disease/metabolism/therapy ; Rotenone/toxicity ; Signal Transduction ; Toll-Like Receptor 4 ; }, abstract = {BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in PD pathogenesis, known as the microbiota-gut-brain axis. As an approach to re-establishing a normal microbiota community, fecal microbiota transplantation (FMT) has exerted beneficial effects on PD in recent studies. Here, in this study, we established a chronic rotenone-induced PD mouse model to evaluate the protective effects of FMT treatment on PD and to explore the underlying mechanisms, which also proves the involvement of gut microbiota dysbiosis in PD pathogenesis via the microbiota-gut-brain axis.<br><br>RESULTS: We demonstrated that gut microbiota dysbiosis induced by rotenone administration caused gastrointestinal function impairment and poor behavioral performances in the PD mice. Moreover, 16S RNA sequencing identified the increase of bacterial genera Akkermansia and Desulfovibrio in fecal samples of rotenone-induced mice. By contrast, FMT treatment remarkably restored the gut microbial community, thus ameliorating the gastrointestinal dysfunctions and the motor deficits of the PD mice. Further experiments revealed that FMT administration alleviated intestinal inflammation and barrier destruction, thus reducing the levels of systemic inflammation. Subsequently, FMT treatment attenuated blood-brain barrier (BBB) impairment and suppressed neuroinflammation in the substantia nigra (SN), which further decreased the damage of dopaminergic neurons. Additional mechanistic investigation discovered that FMT treatment reduced lipopolysaccharide (LPS) levels in the colon, the serum, and the SN, thereafter suppressing the TLR4/MyD88/NF-&#x3ba;B signaling pathway and its downstream pro-inflammatory products both in the SN and the colon.<br><br>CONCLUSIONS: Our current study demonstrates that FMT treatment can correct the gut microbiota dysbiosis and ameliorate the rotenone-induced PD mouse model, in which suppression of the inflammation mediated by the LPS-TLR4 signaling pathway both in the gut and the brain possibly plays a significant role. Further, we prove that rotenone-induced microbiota dysbiosis is involved in the genesis of PD via the microbiota-gut-brain axis. Video abstract.}, }
@article {pmid34784410, year = {2021}, author = {Wu, J and Qiu, M and Zhang, C and Zhang, C and Wang, N and Zhao, F and Lv, L and Li, J and Lyu-Bu, AGA and Wang, T and Zhao, B and You, S and Wu, Y and Wang, X}, title = {Type 3 resistant starch from Canna edulis modulates obesity and obesity-related low-grade systemic inflammation in mice by regulating gut microbiota composition and metabolism.}, journal = {Food &amp; function}, volume = {12}, number = {23}, pages = {12098-12114}, doi = {10.1039/d1fo02208c}, pmid = {34784410}, issn = {2042-650X}, mesh = {Animals ; Dysbiosis/metabolism ; Gastrointestinal Microbiome/*drug effects/genetics ; Inflammation/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/*metabolism ; Resistant Starch/*pharmacology ; Zingiberales/*chemistry ; }, abstract = {Obesity is a most prevalent human health problem. Several studies showed that appropriate modulation of gut microbiota could help reshape the metabolic profile of obese individuals, thereby altering the development of obesity. A nutritional strategy for treating obesity includes prebiotics. Type 3 Resistant Starch from Canna edulis (Ce-RS3) is a dietary fiber that exerts potential effects on the intestinal microbial community; however, the metabolic landscape and anti-obesity mechanism remain unclear. In the present study, obese mice were treated with Ce-RS3, and 16S rRNA gene sequencing and metabolomics were used to measure changes in gut microbiota and fecal metabolic profiles, respectively. At the end of the treatment (13 weeks), we observed slow weight gain in the mice, and pathological damage and inflammation were substantially reduced. Ce-RS3 constructs a healthy gut microbiota structure and can enhance intestinal immunity and reduce metabolic inflammation. Ce-RS3 increased the diversity of gut microbiota with enrichment of Bifidobacterium and Roseburia. Ce-RS3 regulated the systemic metabolic dysbiosis in obese mice and adjusted 26 abnormal metabolites in amino acids and lipids metabolism, many of which are related to the microbiome. More importantly, we found that the anti-obesity effect of Ce-RS3 can be transferred by fecal transplantation. The beneficial effects of Ce-RS3 might derive from gut microbiota changes, which might improve obesity and metabolic inflammation by altering host-microbiota interactions with impacts on the metabolome. In conclusion, Ce-RS3 can be used as a prebiotic with potential value for the treatment of obesity.}, }
@article {pmid34782684, year = {2021}, author = {Große, K and Ohm, D and Würstle, S and Brozat, JF and Schmid, RM and Trautwein, C and Stallmach, A and Bruns, T and Reuken, PA}, title = {Clinical characteristics and outcome of patients with enterococcal liver abscess.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {22265}, pmid = {34782684}, issn = {2045-2322}, support = {SFB1382 Project ID 403114013/B07//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Aged ; Aged, 80 and over ; Comorbidity ; Cross-Sectional Studies ; Disease Management ; Disease Susceptibility ; *Enterococcus ; Female ; Germany/epidemiology ; Gram-Positive Bacterial Infections/*diagnosis/epidemiology/*microbiology ; Humans ; Liver Abscess, Pyogenic/*diagnosis/epidemiology/*microbiology ; Male ; Middle Aged ; Patient Outcome Assessment ; Prognosis ; Retrospective Studies ; Symptom Assessment ; }, abstract = {Epidemiology of bacteria isolated from pyogenic liver abscesses change, and an increase in enterococci has been reported in European hospitals. The aim of this study was to investigate the clinical characteristics and outcome of enterococcal PLA. We performed a retrospective analysis of patients with microbiologically confirmed PLA at three German university centers. Indicators of enterococcal PLA were determined using binary logistic regression, and survival analysis was performed using Kaplan-Meier statistics and Cox regression analysis. Enterococci were isolated in 51/133 (38%) patients with PLA. Patients with enterococcal PLA had smaller abscess diameter (4.8 vs. 6.7 cm, p = 0.03) than patients with non-enterococcal PLA, but had more frequent polymicrobial culture results. In univariate logistic regression analysis, alcohol abuse (OR 3.94, 95% CI 1.24-12.49, p = 0.02), hepatobiliary malignancies (OR 3.90, 95% CI 1.86-8.18, p < 0.001) and cirrhosis (OR 6.36, 95% CI 1.27-31.96, p = 0.02) were associated with enterococcal PLA. Patients with enterococcal PLA had a higher mortality than patients with non-enterococcal PLA (hazard ratio 2.92; 95% confidence interval 1.09-7.80; p = 0.03), which remained elevated even after excluding patients with hepatobiliary malignancies, cirrhosis, and transplant recipients in a sensitivity analysis. The increased mortality was associated with non-fecal enterococci but not in patients with Enterococcus faecalis. In this retrospective, multicenter study, enterococcal PLA was common and indicated an increased risk of mortality, underscoring the need for close clinical monitoring and appropriate treatment protocols in these patients.}, }
@article {pmid34781411, year = {2022}, author = {Sivaraj, S and Copeland, JK and Malik, A and Pasini, E and Angeli, M and Azhie, A and Husain, S and Kumar, D and Allard, J and Guttman, DS and Humar, A and Bhat, M}, title = {Characterization and predictive functional profiles on metagenomic 16S rRNA data of liver transplant recipients: A longitudinal study.}, journal = {Clinical transplantation}, volume = {36}, number = {2}, pages = {e14534}, doi = {10.1111/ctr.14534}, pmid = {34781411}, issn = {1399-0012}, mesh = {Animals ; *Gastrointestinal Microbiome/genetics ; Humans ; *Liver Transplantation ; Longitudinal Studies ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Long-term survival after Liver Transplantation (LT) is often compromised by infectious and metabolic complications. We aimed to delineate alterations in intestinal microbiome (IM) over time that could contribute to medical complications compromising long-term survival following LT. Fecal samples from LT recipients were collected at 3 months (3 M) and 6 months (6 M) post-LT. The bacterial DNA was extracted using E.Z.N.A. Stool DNA Kit and 16S rRNA gene sequencing at V4 hypervariable region was performed. DADA2 and Phyloseq was implemented to analyze the taxonomic composition. Differentially abundant taxa were identified by metagenomeSeq and LEfSe. Piphillin, an Inferred functional metagenomic analysis tool was used to study the bacterial functional content. For comparison, healthy samples were extracted from NCBI and analyzed similarly. The taxonomic &amp; functional profiles of LT recipients were validated with metagenomic sequencing data from animals exposed to immunosuppressants using Venny. Our findings provide a new perspective on longitudinal increase in specific IM communities post-LT along with an increase in bacterial genes associated with metabolic and infectious disease.}, }
@article {pmid34781002, year = {2022}, author = {Chen, CC and Chiu, CH}, title = {Current and future applications of fecal microbiota transplantation for children.}, journal = {Biomedical journal}, volume = {45}, number = {1}, pages = {11-18}, pmid = {34781002}, issn = {2320-2890}, mesh = {*Autism Spectrum Disorder/complications ; Child ; *Clostridium Infections ; Diarrhea/complications ; Ecosystem ; Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases/complications/therapy ; Recurrence ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a new and adequate route to modify the microbial ecosystem in gastrointestinal tract of the hosts. Intestinal microbiota is highly associated with human health and disease. According to the reports of human clinical trials or case series, the application of FMT ranged from Clostridiodes difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome, refractory diarrhea, diabetes mellitus, metabolic syndrome, and even neurologic diseases, including Parkinson disease, and neuropsychiatric disorder (autism spectrum disorder, ASD). Although the current allowed indication of FMT is CDI in Taiwan, more application and development are expectable in the future. There is a relative rare data available for children in application of fecal microbiota transplantation. Thus, we review previous published research inspecting FMT in children, and address particular considerations when conducting FMT in pediatric patients.}, }
@article {pmid34775940, year = {2021}, author = {Nakamura, T and Sugimoto, R and Harada, S and Nobori, S and Ushigome, H and Yoshikawa, M}, title = {Hand-Assisted Laparoscopic Subtotal Colectomy for Ogilvie Syndrome Associated With Idiopathic Fibrosis of Colon After Simultaneous Pancreas Kidney Transplant.}, journal = {Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation}, volume = {19}, number = {12}, pages = {1348-1351}, doi = {10.6002/ect.2021.0306}, pmid = {34775940}, issn = {2146-8427}, mesh = {Colectomy/adverse effects ; *Colitis/pathology ; *Colonic Pseudo-Obstruction/diagnostic imaging/etiology ; Female ; Fibrosis ; *Hand-Assisted Laparoscopy/adverse effects ; Humans ; *Kidney Transplantation/adverse effects ; Middle Aged ; Pancreas/pathology/surgery ; Treatment Outcome ; }, abstract = {Ogilvie syndrome (acute colonic pseudo-obstruction) is a rare, acquired, life-threatening disorder for which treatment plans vary from simple observation to surgical intervention. Ogilvie syndrome has been reported in patients after renal or liver transplant, but its occurrence after simultaneous pancreas-kidney transplant is rare. Herein, we present the case of a 45-year-old female recipient of a deceased donor simultaneous pancreas-kidney transplant who developed Ogilvie syndrome 10 days after a previous fecal ileus that had resolved at posttransplant week 3. She demonstrated Ogilvie syndrome with obstructive colitis features (severe abdominal pain and high-grade fever), which we immediately treated with colonic decompensation by placement of a transanal ileus tube. After several screening examinations and discontinuation of unnecessary medicines, we were not able to confirm the cause of Ogilvie syndrome in our patient. After 2 weeks, the patient remained unresponsive to the conservative treatment, and so hand-assisted laparoscopic subtotal colectomy was performed to remove the dilated colon. Her symptoms gradually resolved after surgery. Histologically, we confirmed submucosal fibrotic changes, especially at the distal end of the resected colon, without evidence of amyloidosis, and the number of Auerbach plexus ganglia had decreased. Nevertheless, we observed no degenerated appearance of ganglion cells in the Auerbach plexus or the Meissner plexus. After exclusion of several collagen diseases, including systemic sclerosis, we determined that idiopathic colonic fibrosis was the likely cause of Ogilvie syndrome in our patient. When surgery is indicated in transplant patients with Ogilvie syndrome with obstructive colitis features, colectomy should be considered.}, }
@article {pmid34775405, year = {2022}, author = {Kühn, F and Hasenhütl, SM and Hofmann, FO and Wirth, U and Drefs, M and Werner, J and Schiergens, TS}, title = {Endoscopic Vacuum Therapy for Left-Sided Colorectal Anastomotic Leak Without Fecal Diversion.}, journal = {Diseases of the colon and rectum}, volume = {65}, number = {3}, pages = {421-428}, doi = {10.1097/DCR.0000000000001959}, pmid = {34775405}, issn = {1530-0358}, mesh = {Anastomotic Leak/etiology/physiopathology/surgery/*therapy ; *Endoscopy, Digestive System/instrumentation/methods ; Female ; Humans ; Male ; Middle Aged ; *Negative-Pressure Wound Therapy/instrumentation/methods ; Patient Selection ; *Proctocolectomy, Restorative/adverse effects/methods ; Rectal Diseases/surgery ; Reoperation/statistics &amp; numerical data ; Retrospective Studies ; Sigmoid Diseases/surgery ; Treatment Outcome ; }, abstract = {BACKGROUND: Endoscopic vacuum therapy for the treatment of rectal anastomotic leak has been shown to be effective and safe. The majority of patients are treated after fecal diversion to avoid further septic complications.<br><br>OBJECTIVE: To report the effectiveness of endoscopic vacuum therapy for rectal anastomotic leak without diversion compared to secondary stoma creation.<br><br>DESIGN: Retrospective cohort analysis.<br><br>SETTINGS: University hospital, single-center.<br><br>PATIENTS: Patients undergoing sigmoid or rectal resection without fecal diversion during primary surgery who were treated with endoscopic vacuum therapy for clinically relevant anastomotic leak.<br><br>MAIN OUTCOME MEASURES: Treatment success (sepsis control, granulation and closure of the leak cavity, and no subsequent interventional or surgical procedure required); treatment duration; complications associated with endoscopic vacuum therapy; outpatient treatment; and restoration of intestinal continuity in diverted patients.<br><br>RESULTS: Fifty-seven patients were included. In 20 patients (35%), endoscopic vacuum therapy was initiated without secondary diversion since the leak was extraperitoneal, and the sponge could be placed into the leak cavity with an adequate seal toward the lumen. In 18 patients (90%), this approach was successful. None of these patients required subsequent diversion in the further course of their disease. In two patients, secondary diversion was necessary due to treatment failure. Balloon dilatation for luminal stenosis was required in two patients. When comparing patient and treatment characteristics of patients with and without a stoma, including treatment success and duration, no significant differences were found. Restoration of intestinal continuity was achieved in 69% of diverted patients.<br><br>LIMITATIONS: Unrandomized, retrospective study design; confounding factors of treatment assignment; low patient numbers and short follow-up of diverted patients; and low statistical power.<br><br>CONCLUSION: In this single-institution study, endoscopic vacuum therapy for rectal anastomotic leak was successful in 90% of patients without diversion with regard to sepsis control, granulation of the leak cavity, avoidance of surgery, and long-term stoma-free survival. See Video Abstract at http://links.lww.com/DCR/B737.TERAPIA ENDOSC&#xd3;PICA POR ASPIRACI&#xd3;N AL VAC&#xcd;O EN CASOS DE FUGA ANASTOM&#xd3;TICA RECTO-C&#xd3;LICA IZQUIERDA SIN OSTOM&#xcd;A DE PROTECCI&#xd3;NANTECEDENTES:Se ha demostrado que la terapia endosc&#xf3;pica por aspiraci&#xf3;n al vac&#xed;o en casos de fuga anastom&#xf3;tica recto-c&#xf3;lica izquierda en el tratamiento de la fuga anastom&#xf3;tica rectal es eficaz y segura. La mayor&#xed;a de los casos beneficiaron del tratamiento despu&#xe9;s de la confeci&#xf3;n de un ostom&#xed;a de protecci&#xf3;n para evitar m&#xe1;s complicaciones s&#xe9;pticas.OBJETIVO:Demostrar la efectividad de la terapia endosc&#xf3;pica por aspiraci&#xf3;n al vac&#xed;o en casos de fuga anastom&#xf3;tica recto-c&#xf3;lica izquierda sin ostom&#xed;a de protecci&#xf3;n comparada con los casos que tuvieron la creaci&#xf3;n de una ostom&#xed;a secundaria.DISE&#xd1;O:An&#xe1;lisis de cohortes de tipo retrospectivo.AJUSTE:Hospital universitario, unic&#xe9;ntrico.PACIENTES:Aquellos pacientes sometidos a una resecci&#xf3;n sigmoidea o rectal sin ostom&#xed;a de protecci&#xf3;n durante una cirug&#xed;a primaria, y que fueron tratados con terapia endosc&#xf3;pica por aspiraci&#xf3;n al vac&#xed;o en caso de fuga anastom&#xf3;tica cl&#xed;nicamente relevante.PRINCIPALES MEDIDAS DE RESULTADO:Tratamiento exitoso (control de la sepsis, granulaci&#xf3;n y cierre de la cavidad de la fuga, sin requerir procedimiento quir&#xfa;rgico o intervenci&#xf3;n ulteterior); duraci&#xf3;n del tratamiento; complicaciones asociadas con la terapia endosc&#xf3;pica por aspiraci&#xf3;n al vac&#xed;o; tratamiento ambulatorio; restablecimiento de la continuidad intestinal en los pacientes portadores de ostom&#xed;a.RESULTADOS:Se incluyeron 57 pacientes. En 20 pacientes (35%), se inici&#xf3; la terapia endosc&#xf3;pica por aspiraci&#xf3;n al vac&#xed;o sin derivaci&#xf3;n secundaria, ya que la fuga era extraperitoneal y la esponja pod&#xed;a colocarse en la cavidad de la fuga con un sellado adecuado hacia el lumen. En 18 pacientes (90%), este enfoque fue exitoso. Ninguno de estos pacientes requiri&#xf3; una derivaci&#xf3;n posterior durante la evoluci&#xf3;n de la enfermedad. En dos pacientes, fue necesaria una derivaci&#xf3;n secundaria debido al fracaso del tratamiento. Se requiri&#xf3; dilataci&#xf3;n con bal&#xf3;n por estenosis luminal en dos pacientes. Al comparar las caracter&#xed;sticas de los pacientes y del tratamiento con y sin ostom&#xed;a, incluido el &#xe9;xito y la duraci&#xf3;n del tratamiento, no se encontraron diferencias significativas. El restablecimiento de la continuidad intestinal se logr&#xf3; en el 69% de los pacientes derivados.LIMITACIONES:Dise&#xf1;o de estudio retrospectivo no aleatorio; factores de confusi&#xf3;n en la asignaci&#xf3;n del tratamiento; escaso n&#xfa;mero de pacientes y seguimiento a corto plazo de los pacientes ostomizados; bajo poder estad&#xed;stico.CONCLUSI&#xd3;N:En este estudio de una sola instituci&#xf3;n, la terapia al vac&#xed;o por v&#xed;a endosc&#xf3;pica en casos de fuga anastom&#xf3;tica rectal fue exitosa en el 90% de los pacientes sin derivaci&#xf3;n con respecto al control de la sepsis, granulaci&#xf3;n de la cavidad de la fuga, como se evit&#xf3; la cirug&#xed;a y la sobrevida sin ostom&#xed;a a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B737. (Traducci&#xf3;n-Dr. Xavier Delgadillo).}, }
@article {pmid34773257, year = {2022}, author = {Kim, ER and Park, JS and Kim, JH and Oh, JY and Oh, IJ and Choi, DH and Lee, YS and Park, IS and Kim, S and Lee, DH and Cheon, JH and Bae, JW and Lee, M and Cho, JW and An, IB and Nam, EJ and Yang, SI and Lee, MS and Bae, SH and Lee, YH}, title = {A GLP-1/GLP-2 receptor dual agonist to treat NASH: Targeting the gut-liver axis and microbiome.}, journal = {Hepatology (Baltimore, Md.)}, volume = {75}, number = {6}, pages = {1523-1538}, doi = {10.1002/hep.32235}, pmid = {34773257}, issn = {1527-3350}, mesh = {Animals ; Body Weight ; Diet, High-Fat/adverse effects ; Glucagon-Like Peptide 1/metabolism ; Glucagon-Like Peptide-2 Receptor/metabolism ; Inflammation/metabolism ; Liver/pathology ; Liver Cirrhosis/complications ; Mice ; Mice, Inbred C57BL ; *Microbiota ; *Non-alcoholic Fatty Liver Disease/pathology ; }, abstract = {BACKGROUND AND AIMS: Currently there is no Food and Drug Administration-approved drug to treat NAFLD and NASH, the rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut-liver axis in their pathogenesis, we investigated the therapeutic effect of a long-acting dual agonist of glucagon-like peptide (GLP)-1 and GLP-2 receptors in mice with NAFLD/NASH.<br><br>APPROACH AND RESULTS: C57BL/6J mice were fed a choline-deficient high-fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1-Fc, GLP2-Fc, or GLP1/2-Fc fusion (GLP1/2-Fc) subcutaneously every 2 days for 4 weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were used to evaluate direct peptide effect. Immunohistochemistry, quantitative PCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well-developed NASH phenotypes. GLP1/2-Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, and goblet cells of intestine compared with a vehicle group. Similar effects of GLP1/2-Fc were found in in vitro cell systems. GLP1/2-Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) gain further insight into the mechanism of GLP1/2-Fc-mediated protection. We confirmed that FMT exerted an additive effect on GLP1-Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation, and hepatic fibrosis.<br><br>CONCLUSIONS: A long-acting dual agonist of GLP-1 and GLP-2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.}, }
@article {pmid34769321, year = {2021}, author = {Gao, T and Wang, Z and Dong, Y and Cao, J and Chen, Y}, title = {Melatonin-Mediated Colonic Microbiota Metabolite Butyrate Prevents Acute Sleep Deprivation-Induced Colitis in Mice.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769321}, issn = {1422-0067}, mesh = {Animals ; Antioxidants/pharmacology ; Butyrates/*pharmacology ; Colitis/etiology/pathology/*prevention &amp; control ; Colon/drug effects/*microbiology ; Fecal Microbiota Transplantation/*methods ; Male ; Melatonin/*pharmacology ; Mice ; Mice, Inbred ICR ; Microbiota/*drug effects ; Sleep Deprivation/*complications ; }, abstract = {Radical cure colitis is a severe public health threat worldwide. Our previous studies have confirmed that melatonin can effectively improve gut microbiota disorder and mucosal injury caused by sleep deprivation (SD). The present study further explored the mechanism whereby exogenous melatonin prevented SD-induced colitis. 16S rRNA high-throughput sequencing and metabolomics analysis were used to explore the correlation between SD-induced colitis and intestinal microbiota and metabolite composition in mice. Fecal microbiota transplantation (FMT) and melatonin or butyrate supplementation tests verified the core role of gut microbiota in melatonin-alleviating SD-induced colitis. Further, in vitro tests studied the modulatory mechanism of metabolite butyrate. The results demonstrated that SD leads to reductions in plasma melatonin levels and colonic Card9 expression and consequent occurrence of colitis and gut microbiota disorder, especially the downregulation of Faecalibacterium and butyrate levels. The FMT from SD-mice to normal mice could restore SD-like colitis, while butyrate supplementation to SD-mice inhibited the occurrence of colitis, but with no change in the plasma melatonin level in both treatments. However, melatonin supplementation reversed all inductions in SD-mice. In intestinal epithelial cells, the inflammatory ameliorative effect of butyrate was blocked with pretreatments of HDAC3 agonist and HIF-1α antagonist but was mimicked by GSK-3β and p-P65 antagonists. Therefore, the administration of MLT may be a better therapy for SD-induced colitis relative to butyrate. A feasible mechanism would involve that melatonin up-regulated the Faecalibacterium population and production of its metabolite butyrate and MCT1 expression and inhibited HDAC3 in the colon, which would allow p-GSK-3β/β-catenin/HIF-1α activation and NF-κB/NLRP3 suppression to up-regulate Card9 expression and suppress inflammation response.}, }
@article {pmid34768867, year = {2021}, author = {Chen, Z and Wang, B and Dong, J and Li, Y and Zhang, S and Zeng, X and Xiao, H and Fan, S and Cui, M}, title = {Gut Microbiota-Derived l-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34768867}, issn = {1422-0067}, support = {81872555, 81803062, 82003399 and 81730086//National Natural Science Foundation of China/ ; 20JCJQJC00100//Science Foundation for Distinguished Young Scholars of Tianjin/ ; }, mesh = {Animals ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome/physiology/radiation effects ; Histidine/metabolism/*pharmacology ; Imidazoles/metabolism/*pharmacology ; Lung Injury/prevention &amp; control ; Male ; Mice ; Mice, Inbred C57BL ; Radiation Injuries/*prevention &amp; control/therapy ; Radiation-Protective Agents/pharmacology ; Thoracic Neoplasms/microbiology/radiotherapy ; }, abstract = {Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived l-Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of l-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. l-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. l-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of l-Histidine, accumulated in peripheral blood and lung tissues following l-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced l-Histidine and ImP are promising radioprotective agents.}, }
@article {pmid34768795, year = {2021}, author = {Popov, J and Caputi, V and Nandeesha, N and Rodriguez, DA and Pai, N}, title = {Microbiota-Immune Interactions in Ulcerative Colitis and Colitis Associated Cancer and Emerging Microbiota-Based Therapies.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34768795}, issn = {1422-0067}, mesh = {Animals ; Colitis, Ulcerative/*microbiology/therapy ; Colitis-Associated Neoplasms/*microbiology/therapy ; Host-Pathogen Interactions ; Humans ; *Microbiota ; Probiotics ; }, abstract = {Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn's disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.}, }
@article {pmid34768480, year = {2021}, author = {Caviglia, GP and De Blasio, F and Vernero, M and Armandi, A and Rosso, C and Saracco, GM and Bugianesi, E and Astegiano, M and Ribaldone, DG}, title = {Efficacy of a Preparation Based on Calcium Butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and Fructooligosaccharides in the Prevention of Relapse in Ulcerative Colitis: A Prospective Observational Study.}, journal = {Journal of clinical medicine}, volume = {10}, number = {21}, pages = {}, pmid = {34768480}, issn = {2077-0383}, abstract = {Several compounds based on short chain fatty acids and/or probiotics/prebiotics have shown promising results in the therapy of ulcerative colitis (UC), possibly due to its key role in restoring gut homeostasis as well as intestinal barrier integrity. Here, we investigated the efficacy of a patented preparation based on calcium butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and fructooligosaccharides (FEEDColon[®], Princeps, Cuneo, Italy) in maintaining remission and improving subjective symptoms and inflammatory indices in patients with UC receiving 5-ASA therapy. A total of 42 patients were prospectively recruited and randomized in 21 patients receiving combination therapy with mesalamine (5-ASA) plus FEEDColon[®] and 21 patients treated with standard 5-ASA therapy. Patients were assessed at baseline, at 6-month, and 12-month follow-up (FU). Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12-month FU) was reached by 32 (76%) patients: 20 (95%) among those treated with 5-ASA + FeedColon[®], and 12 (57%) among those treated with 5-ASA only (p = 0.009). Consistently, patients treated with combination therapy improved subjective symptoms (quality of life, abdominal pain, and stool consistency) and reduced FC values, while those treated with 5-ASA alone, improved neither subjective symptoms nor FC during the FU. In conclusion, FEEDColon[®] supplementation appears to be a valid add-on therapy for the maintenance of remission in patients with UC. Further multicentre, placebo-controlled, double-blind clinical trials are needed to validate our results on larger cohorts of patients with UC.}, }
@article {pmid34764881, year = {2021}, author = {Yang, Y and Jiang, X and Pandol, SJ and Han, YP and Zheng, X}, title = {Green Plant Pigment, Chlorophyllin, Ameliorates Non-alcoholic Fatty Liver Diseases (NAFLDs) Through Modulating Gut Microbiome in Mice.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {739174}, pmid = {34764881}, issn = {1664-042X}, abstract = {Non-alcoholic fatty liver diseases (NAFLDs) along with metabolic syndrome and Type-2 diabetes (T2D) are increasingly prevalent worldwide. Without an effective resolution, simple hepatic steatosis may lead to non-alcoholic steatohepatitis (NASH), characterized by hepatocyte damage, chronic inflammation, necrosis, fatty degeneration, and cirrhosis. The gut microbiome is vital for metabolic homeostasis. Conversely, dysbiosis contributes to metabolic diseases including NAFLD. Specifically, diet composition is critical for the enterotype of gut microbiota. We reasoned that green pigment rich in vegetables may modulate the gut microbiome for metabolic homeostasis. In this study, C57BL/6 mice under a high fat diet (HFD) were treated with sodium copper chlorophyllin (CHL), a water-soluble derivative of chlorophyll, in drinking water. After 28 weeks of HFD feeding, liver steatosis was established accompanied by gut microbiota dysbiosis, intestinal impairment, endotoxemia, systemic inflammation, and insulin resistance. Administration of CHL effectively alleviated systemic and intestinal inflammation and maintained tight junction in the intestinal barrier. CHL rebalanced gut microbiota in the mice under high fat feeding and attenuated hepatic steatosis, insulin resistance, dyslipidemia, and reduced body weight. Fecal flora transplants from the CHL-treated mice ameliorated steatosis as well. Thus, dietary green pigment or the administration of CHL may maintain gut eubiosis and intestinal integrity to attenuate systemic inflammation and relieve NASH.}, }
@article {pmid34764691, year = {2021}, author = {Zhou, H and Yuan, Y and Wang, H and Xiang, W and Li, S and Zheng, H and Wen, Y and Ming, Y and Chen, L and Zhou, J}, title = {Gut Microbiota: A Potential Target for Cancer Interventions.}, journal = {Cancer management and research}, volume = {13}, number = {}, pages = {8281-8296}, pmid = {34764691}, issn = {1179-1322}, abstract = {The gut microbiota plays a crucial role in many physiological processes in the human body. Dysbiosis can disrupt the intestinal barrier and alter metabolism and immune responses, leading to the development of diseases. Over the past few decades, evidence has accumulated linking changes in the composition of the gut microbiota to dozens of seemingly unrelated conditions, including cancer. Overall, the gut microbiota mainly affects the occurrence and development of cancer by damaging host DNA, forming and maintaining a pro-inflammatory environment, and affecting host immune responses. In addition, the gut microbiota can also affect the efficacy and toxicity of chemotherapy, radiotherapy, and immunotherapy. Scientists attempt to improve the efficacy and decrease the toxicity of these treatment modalities by fine-tuning the gut microbiota. The aim of this review is to assist researchers and clinicians in developing new strategies for the detection and treatment of tumors by providing the latest information on the intestinal microbiome and cancer, as well as exploring potential application prospects and mechanisms of action.}, }
@article {pmid34764444, year = {2021}, author = {Rolling, T and Zhai, B and Gjonbalaj, M and Tosini, N and Yasuma-Mitobe, K and Fontana, E and Amoretti, LA and Wright, RJ and Ponce, DM and Perales, MA and Xavier, JB and van den Brink, MRM and Markey, KA and Peled, JU and Taur, Y and Hohl, TM}, title = {Haematopoietic cell transplantation outcomes are linked to intestinal mycobiota dynamics and an expansion of Candida parapsilosis complex species.}, journal = {Nature microbiology}, volume = {6}, number = {12}, pages = {1505-1515}, pmid = {34764444}, issn = {2058-5276}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 AI139632/AI/NIAID NIH HHS/United States ; R21 AI156157/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; R01 AI100288/AI/NIAID NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; R01 AI093808/AI/NIAID NIH HHS/United States ; R21 AI105617/AI/NIAID NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/isolation &amp; purification ; Biodiversity ; Candida parapsilosis/genetics/*growth &amp; development/physiology ; Dysbiosis/immunology/microbiology ; Feces/microbiology ; Fungi/classification/genetics/isolation &amp; purification ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Humans ; Intestines/immunology/microbiology ; Prospective Studies ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {Allogeneic haematopoietic cell transplantation (allo-HCT) induces profound shifts in the intestinal bacterial microbiota. The dynamics of intestinal fungi and their impact on clinical outcomes during allo-HCT are not fully understood. Here we combined parallel high-throughput fungal ITS1 amplicon sequencing, bacterial 16S amplicon sequencing and fungal cultures of 1,279 faecal samples from a cohort of 156 patients undergoing allo-HCT to reveal potential trans-kingdom dynamics and their association with patient outcomes. We saw that the overall density and the biodiversity of intestinal fungi were stable during allo-HCT but the species composition changed drastically from day to day. We identified a subset of patients with fungal dysbiosis defined by culture positivity (n = 53) and stable expansion of Candida parapsilosis complex species (n = 19). They presented with distinct trans-kingdom microbiota profiles, characterized by a decreased intestinal bacterial biomass. These patients had worse overall survival and higher transplant-related mortality independent of candidaemia. This expands our understanding of the clinical significance of the mycobiota and suggests that targeting fungal dysbiosis may help to improve long-term patient survival.}, }
@article {pmid34761734, year = {2022}, author = {Hou, K and Zhang, S and Wu, Z and Zhu, D and Chen, F and Lei, ZN and Liu, W and Xiao, C and Chen, ZS}, title = {Reconstruction of intestinal microecology of type 2 diabetes by fecal microbiota transplantation: Why and how.}, journal = {Bosnian journal of basic medical sciences}, volume = {22}, number = {3}, pages = {315-325}, pmid = {34761734}, issn = {1840-4812}, mesh = {*Diabetes Mellitus, Type 1/metabolism ; *Diabetes Mellitus, Type 2/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Insulin Resistance ; }, abstract = {Type 2 diabetes (T2D) is a chronic metabolic disease characterized by hyperglycemia due to insulin resistance. Mounting evidence has correlated T2D to alterations in the composition of gut microbiota. Accordingly, targeting the gut microbiota has become an emerging strategy for T2D management. The aim of this article is to get a better insight into the rationale for targeting gut microbiota in T2D treatment. Thus, we herein reviewed the change of gut microbiota composition in T2D, factors shaping gut microbiota, and potential mechanisms behind the contribution of gut microbiota to T2D pathogenesis. At present, it has become possible to use intestinal microorganism capsules, bacteria liquid, and other preparations to carry out fecal microbiota transplantation for the treatment and intervention of T2D with insulin resistance and immune-mediated type 1 diabetes (T1D).}, }
@article {pmid34760906, year = {2021}, author = {Clancy, AK and Gunaratne, AW and Borody, TJ}, title = {Dietary Management for Faecal Microbiota Transplant: An International Survey of Clinical and Research Practice, Knowledge and Attitudes.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {653653}, pmid = {34760906}, issn = {2296-861X}, abstract = {Faecal microbiota transplantation (FMT) involves homogenisation and infusion of stool from a healthy, highly screened individual into the bowel of an unwell recipient. Dietary intake is an important modulator of the gut microbiota. Currently there are no clinical practice recommendations available to provide patients or stool donors with dietary advice for FMT. This study aimed to conduct an international survey to examine health professionals and researchers' attitudes, knowledge and current practice recommendations for diet in patients undergoing FMT. An online, cross-sectional, international survey comprising of health professionals and researchers managing patients undergoing treatment with FMT was conducted between July-October 2020. Purposeful and snowball sampling techniques were employed to identify eligible participants who were sent an email invitation and two email reminders with a link to participate in the electronic survey. The survey comprised 21 questions covering demographics, current practice, beliefs and future directions regarding FMT and diet. Closed responses were calculated as proportions of total responses. Open-ended responses were systematically categorised. Common themes were identified from recurring categories. Fifty-eight (M 60%) participants from 14 countries completed the survey. Participants were gastroenterologists (55%), with 1-5 years' experience working in FMT (48%) and treating up to ten patients with FMT per month (74%). Participants agreed that diet was an important consideration for FMT recipients and stool donors (both 71%), and that it would affect the outcomes of FMT. However, they did not feel confident in providing dietary advice to patients, nor that there was sufficient evidence to provide dietary advice and this was reflected in their practice. Future research must collect information on the dietary intake of patients and donors to better understand the relationship between diet and FMT outcomes. In clinical practice, promotion of healthy eating guidelines aligns with current practice and literature.}, }
@article {pmid34759928, year = {2021}, author = {Pan, P and Atkinson, SN and Taylor, B and Zhu, H and Zhou, D and Flejsierowicz, P and Wang, LS and Morse, M and Liu, C and Gunsolus, IL and Chen, X}, title = {Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {749002}, pmid = {34759928}, issn = {1664-3224}, support = {R01 AI125334/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Caco-2 Cells ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/genetics ; Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation ; Humans ; Intestinal Mucosa/*drug effects/metabolism ; Lung/drug effects ; Male ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Permeability/drug effects ; RNA, Ribosomal, 16S ; Signal Transduction/drug effects ; Transplantation, Homologous ; Vitamin A/*pharmacology ; Vitamins/*pharmacology ; Mice ; }, abstract = {Graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). An impaired intestinal epithelial barrier is an important component of GVHD pathogenesis. However, contributing host factors that modulate mucosal barrier integrity during GVHD are poorly defined. We hypothesized that vitamin A and retinoic acid (RA) exert positive impacts on maintaining intestinal barrier function after HSCT, thus preventing or dampening GVHD severity. Unexpectedly, we found that exogenous RA increased intestinal permeability of recipient mice after allogeneic HSCT. Serum bacterial endotoxin levels were significantly higher in GVHD mice fed a vitamin A-high (VAH) diet compared to those fed a vitamin A-normal (VAN) diet, indicating a more compromised intestinal barrier function. Furthermore, VAH mice showed more severe lung GVHD with increased donor T cell infiltration in this tissue and died significantly faster than VAN recipients. 16S rRNA sequencing of fecal samples revealed significant differences in the diversity and composition of gut microbiota between VAN and VAH transplant recipients. Collectively, we show that retinoic acid signaling may negatively impact intestinal barrier function during GVHD. Mild vitamin A supplementation is associated with increased lung GVHD and more profound gut dysbiosis. Micronutrients such as vitamin A could modulate complications of allogeneic HSCT, which may be mediated by shaping gut microbiota.}, }
@article {pmid34758276, year = {2022}, author = {Moutsoglou, DM}, title = {2021 American Thoracic Society BEAR Cage Winning Proposal: Microbiome Transplant in Pulmonary Arterial Hypertension.}, journal = {American journal of respiratory and critical care medicine}, volume = {205}, number = {1}, pages = {13-16}, pmid = {34758276}, issn = {1535-4970}, support = {T32 HL144472/HL/NHLBI NIH HHS/United States ; }, mesh = {Administration, Oral ; *Awards and Prizes ; Clinical Protocols ; Clinical Trials, Phase I as Topic/*methods ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; Pulmonary Arterial Hypertension/*microbiology/*therapy ; Societies, Medical ; }, }
@article {pmid34755816, year = {2021}, author = {Mendes, ET and Salomão, MC and Tomichi, LM and Oliveira, MS and Graça, M and Rossi, F and Sapadao, F and Guimarães, T and Rocha, V and Costa, SF}, title = {Effectiveness of surveillance cultures for high priority multidrug-resistant bacteria in hematopoietic stem cell transplant units.}, journal = {Revista do Instituto de Medicina Tropical de Sao Paulo}, volume = {63}, number = {}, pages = {e77}, pmid = {34755816}, issn = {1678-9946}, mesh = {Carbapenem-Resistant Enterobacteriaceae/isolation &amp; purification ; Drug Resistance, Multiple, Bacterial ; Enterobacteriaceae Infections/*epidemiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Pseudomonas Infections/*epidemiology ; Pseudomonas aeruginosa/isolation &amp; purification ; Vancomycin-Resistant Enterococci/isolation &amp; purification ; }, abstract = {Surveillance strategies to detect colonization are an important tool to prevent and control the spread of microorganisms in hematopoietic stem cell transplant (HSCT) units. The aim of this study was to evaluate routine surveillance cultures for screening colonization and infection by carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPa), and vancomycin-resistant enterococci (VRE). Surveillance cultures were collected (1,323 samples) from 200 patients admitted to an HSCT unit over one year; swabs were taken on admission and then weekly. We compared the positivity of cultures for each site, agent, clinical and epidemiological data according to the colonization status. Infection due to multidrug-resistant organisms (MDROs) occurred in 52 (21.5%) patients, 45 (86.5%) due to blood stream infection; 12 (23%) patients had a positive surveillance culture before the infection. Cultures of 554 (41.8%) samples were performed for CRPa, 413 (31.2%) for VRE and 356 (27%) for CRE. Of these, 179 (13.5%) were positive. Colonization by any MDRO, CRE or CRPa was associated with increased risk of infection (P < 0.05), but not with death. Previous colonization by an MDRO was a significant risk for infection by these pathogens, specially by CRE. Overall, rectal swabs had the highest positivity rate compared with other sites, oropharynx swabs were an option for CRPa, and fecal cultures showed low positivity. Although the impact of the strategy on the mortality of patients undergoing HSCT is not clear, routine VRE surveillance should be questioned with regard to patients undergoing auto-HSCT due to the additional cost and little impact on survival rates.}, }
@article {pmid34754163, year = {2021}, author = {Baldi, S and Mundula, T and Nannini, G and Amedei, A}, title = {Microbiota shaping - the effects of probiotics, prebiotics, and fecal microbiota transplant on cognitive functions: A systematic review.}, journal = {World journal of gastroenterology}, volume = {27}, number = {39}, pages = {6715-6732}, pmid = {34754163}, issn = {2219-2840}, mesh = {Cognition ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {BACKGROUND: Dementia is a chronic progressive neurological disease affecting millions of people worldwide, and represents a relevant economic burden for healthcare systems. Although its pathogenesis is still unknown, recent findings have reported that a dysregulated gut-brain axis communication, a fundamental relationship mediated by several host and microbial molecules, is associated with cognitive disorders. In addition, gut microbiota manipulation reduces neuroinflammation, improving cognitive function by restoring the functional gut-brain axis.<br><br>AIM: To better define the effects of probiotics, prebiotics, synbiotics, and fecal microbiota transplant (FMT) on cognitive function.<br><br>METHODS: We performed a literature search of human randomized clinical trials to examine the effects of the administration of probiotics, prebiotics, synbiotics, or FMT on cognition outcomes in healthy or sick people of every age, sex, and nationality. We systematically searched Embase, Medline/PubMed, Cochrane Library, central and clinicaltrials.gov databases with a combination of comprehensive terms related to cognition and gut microbiota manipulation. Then we carefully reviewed and synthesized the data by type of study design and setting, characteristics of the studied population, kind of intervention (strain type or mixture type, dosage, and frequency of administration), control treatment, inclusion and exclusion criteria, follow-up duration, and cognitive or memory outcomes.<br><br>RESULTS: After examining the titles and abstracts, the initial literature screening identified 995 articles, but we added 23 papers in our systematic review. The analyses of these selected studies highlighted that both probiotic supplementation and FMT improved cognitive function regardless of the type and posology of administration and the adopted cognitive tests and questionnaires. We found that most of the studies conducted in healthy people showed a significant positive effect of the intervention on at least one of the performed cognitive tests. Regarding unhealthy subjects, while FMT and especially probiotic administration had multiple beneficial effects on different cognitive functions, supplementation with prebiotics did not provide any cognitive improvement.<br><br>CONCLUSION: Probiotic supplementation and FMT may represent a promising strategy to restore gut eubiosis and enhance the cognitive functions of healthy people and patients with neurological disorders.}, }
@article {pmid34752816, year = {2022}, author = {Zhang, S and Chen, Q and Kelly, CR and Kassam, Z and Qin, H and Li, N and ,  and Tian, H and Yang, B and Zhao, D and Ye, C and Lin, Z and Cui, J and Zhou, S and Chen, X and Lv, X and Yang, R}, title = {Donor Screening for Fecal Microbiota Transplantation in China: Evaluation of 8483 Candidates.}, journal = {Gastroenterology}, volume = {162}, number = {3}, pages = {966-968.e3}, doi = {10.1053/j.gastro.2021.11.004}, pmid = {34752816}, issn = {1528-0012}, mesh = {China ; Donor Selection/*methods/*statistics &amp; numerical data ; Fecal Microbiota Transplantation/*statistics &amp; numerical data ; Humans ; }, }
@article {pmid34752587, year = {2021}, author = {Urbonas, T and Ianiro, G and Gedgaudas, R and Sabanas, P and Urba, M and Kiudelis, V and Kiudelis, G and Petkevicius, V and Vitkauskiene, A and Cammarota, G and Gasbarrini, A and Kupcinskas, J}, title = {Fecal Microbiome Transplantation for Recurrent Clostridioides difficile Infection: Treatment Efficacy, Short and Long-term Follow-up Results from Consecutive Case Series.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {30}, number = {4}, pages = {470-476}, doi = {10.15403/jgld-3800}, pmid = {34752587}, issn = {1842-1121}, mesh = {Aged ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; Feces ; Follow-Up Studies ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Many studies have shown a high effectiveness of fecal microbiota transplantation (FMT) in treatment of recurrent or refractory Clostridioides difficile infection (CDI). Nevertheless, data on long term outcomes and complications after FMT are still lacking. We aimed to evaluate the efficacy, the peri- procedural safety profile and the long-term efficacy and safety of FMT for recurrent CDI during a median follow up period of 24 months.<br><br>METHODS: Our study included 60 consecutive patients that were treated from 2015 to 2019 for recurrent CDI. In all patients FMT was performed through the nasoenteric tube placed during gastroscopy. Fresh donor feces were used for FMT from unrelated donors. Pre-FMT preparation included CDI treatment with oral vancomycin 500 mg q.i.d. for at least five days and proton pump inhibitor (PPI) administration before FMT. Follow up data included information about recurrent CDI episodes, early and late complications, health status at 3, 12 and 24 months after FMT.<br><br>RESULTS: FMT was performed for 60 patients (median age 72.5 years) with recurrent CDI. Clinical improvement after the first FMT procedure was observed in 48 patients (80%). Ten of 12 initially non-responding patients had a clinical resolution after a second FMT leading to an increased overall cure rate of 96.7 %. The remaining two patients needed a third FMT with a final overall cure rate of 100%. Nine of 60 patients were under immunosuppressive therapy. Six immunosuppressed patients were in the group of initial responders and the remaining three in the initially non-responder group. We observed a very low rate of adverse events in the short and long-term after FMT. During the first eight weeks after the FMT procedure, the death of three patients occurred, but they were not related to the FMT procedure. Patients were followed up for a median of 20 months, with the range from 12 to 55 months. During the follow-up period no long-term serious adverse events (SAE) were documented.<br><br>CONCLUSIONS: Our study confirms excellent efficacy rates of FMT in the treatment of recurrent CDI. In addition, this study shows that it is possible to avoid short term SAE when FMT is administered via a nasoenteric tube by following a very stringent peri-procedural patient follow-up protocol. Our study also demonstrates good safety with a low rate of long-term adverse events after FMT.}, }
@article {pmid34752586, year = {2021}, author = {Les, A and Iacob, R and Saizu, R and Cotruta, B and Saizu, AI and Iacob, S and Gheorghe, L and Gheorghe, C}, title = {Bowel Ultrasound: a Non-invasive, Easy to Use Method to Predict the Need to Intensify Therapy in Inflammatory Bowel Disease Patients.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {30}, number = {4}, pages = {462-469}, doi = {10.15403/jgld-3726}, pmid = {34752586}, issn = {1842-1121}, mesh = {Biomarkers ; *Colitis, Ulcerative/diagnostic imaging/drug therapy ; *Crohn Disease/diagnosis ; Feces ; Humans ; *Inflammatory Bowel Diseases/diagnostic imaging/therapy ; Intestines ; Leukocyte L1 Antigen Complex ; }, abstract = {BACKGROUND AND AIMS: Bowel ultrasound (BU) is a non-invasive, inexpensive, widely available tool, valuable for inflammatory bowel disease (IBD) assessment. The aim of the present study was to investigate the clinical utility of BU to predict the need to intensify therapy in IBD patients.<br><br>METHODS: One hundred seventeen IBD patients (89 Crohn's disease, and 28 ulcerative colitis) diagnosis established at least 6 months before enrolment, undergoing maintenance therapy were prospectively included in the study. Bowel ultrasound investigated the following parameters: the bowel wall thickness (BWT), loss of wall stratification, the presence of the bowel wall Doppler signal, the visible lymph nodes, the mucosal hyperechoic spots, and the irregular external bowel wall. The patients were followed-up for 6 months, registering the need to escalate the treatment regimen. Subgroup analyses were conducted for patients requiring immediate treatment intensification (37 subjects), due to active disease at baseline and patients with subsequent treatment intensification, in the 6 months follow-up period (21 cases) in comparison to patients that required no therapeutic optimization (59).<br><br>RESULTS: During the follow-up, 49.6% of patients needed treatment escalation. All the investigated BU variables were significantly associated with the main outcome. In the multivariate analysis, the mean BWT (p<0.0001), and the presence of the bowel wall Doppler signal (p=0.007) were independent predictors of the main outcome. For the subgroup analyses: mean BWT (p=0.0001) and the presence of the bowel wall Doppler signal (p=0.01) were independent predictors for immediate treatment intensification (active disease at baseline) and mean BWT (p=0.0003) and the lack of bowel wall stratification (p=0.05) were independent predictors for the need of subsequent therapeutic optimization. Logistic regression prediction models and prediction scores (BU score) had the best AUROC values (>0.91) when compared to traditional biomarkers of active inflammation, such as C reactive protein or fecal calprotectin.<br><br>CONCLUSION: Bowel ultrasound could be used as a non-invasive, easy to use diagnostic tool to predict the need to intensify therapy in patients with IBD.}, }
@article {pmid34752089, year = {2021}, author = {Zhou, F and Li, YL and Zhang, X and Wang, KB and Huang, JA and Liu, ZH and Zhu, MZ}, title = {Polyphenols from Fu Brick Tea Reduce Obesity via Modulation of Gut Microbiota and Gut Microbiota-Related Intestinal Oxidative Stress and Barrier Function.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {48}, pages = {14530-14543}, doi = {10.1021/acs.jafc.1c04553}, pmid = {34752089}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Obesity/drug therapy ; Oxidative Stress ; Phylogeny ; Polyphenols ; Rats ; Tea ; }, abstract = {Fu brick tea (FBT) is a microbial-fermented tea, which is produced by the solid-state fermentation of tea leaves. Previous studies have proved that FBT aqueous extracts could attenuate obesity and gut microbiota dysbiosis. However, the bioactive components in FBT that contribute to these activities remain unclear. In this study, we aimed to investigate the effects of FBT polyphenols (FBTPs) on obesity, gut microbiota, and gut microbiota-related intestinal oxidative stress and barrier function and to further investigate whether the antiobesity effect of FBTPs was dependent on the alteration of gut microbiota. The results showed that FBTP supplementation effectively attenuated obesity in high-fat diet (HFD)-fed rats. FBTP supplementation improved the intestinal oxidative stress and intestinal barrier function, including intestinal inflammation and the integrity of the intestinal barrier. Furthermore, FBTP intervention significantly attenuated HFD-induced gut microbiota dysbiosis, characterized by increased phylogenetic diversity and decreased Firmicutes/Bacteroidetes ratio. Certain core microbes, including Akkermansia muciniphila, Alloprevotella, Bacteroides, and Faecalibaculum, were also found to be improved by FBTPs. Moreover, the antiobesity effect of FBTPs was gut microbiota-dependent, as demonstrated by a fecal microbiota transplantation experiment. Collectively, we concluded that FBTPs reduced obesity by modulating the gut microbiota and gut microbiota-related intestinal oxidative stress and barrier function. Therefore, FBTPs may be used as prebiotic agents to treat obesity and gut microbiota dysbiosis in obese individuals.}, }
@article {pmid34751848, year = {2022}, author = {Donahue, CA and Chaudhry, V and Mantilla, N}, title = {Autologous fecal transplant for the treatment of microcolon due to diversion colitis.}, journal = {Techniques in coloproctology}, volume = {26}, number = {1}, pages = {79-81}, pmid = {34751848}, issn = {1128-045X}, mesh = {*Colitis/etiology/therapy ; Colon/abnormalities ; *Fecal Microbiota Transplantation ; Humans ; *Intestinal Obstruction ; Male ; Young Adult ; }, }
@article {pmid34751747, year = {2022}, author = {Dai, C and Liu, WX}, title = {Refractory Immune Checkpoint Inhibitor-induced Colitis Improved by Fecal Microbiota Transplantation: A Case Report.}, journal = {Inflammatory bowel diseases}, volume = {28}, number = {3}, pages = {e43-e44}, doi = {10.1093/ibd/izab265}, pmid = {34751747}, issn = {1536-4844}, mesh = {*Colitis/chemically induced/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors/adverse effects ; }, }
@article {pmid34750433, year = {2021}, author = {Knudsen, JK and Michaelsen, TY and Bundgaard-Nielsen, C and Nielsen, RE and Hjerrild, S and Leutscher, P and Wegener, G and Sørensen, S}, title = {Faecal microbiota transplantation from patients with depression or healthy individuals into rats modulates mood-related behaviour.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {21869}, pmid = {34750433}, issn = {2045-2322}, mesh = {Adult ; Affect ; Animals ; Behavior, Animal ; Depression/genetics/psychology/*therapy ; Disease Models, Animal ; *Fecal Microbiota Transplantation/psychology ; Female ; Gene Expression ; Humans ; Male ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Rats ; Tight Junction Proteins/genetics ; Young Adult ; }, abstract = {Differences in gut microbiota composition have been observed in patients with major depressive disorder (MDD) compared to healthy individuals. Here, we investigated if faecal microbiota transplantation (FMT) from patients with MDD into rats could induce a depressive-like phenotype. We performed FMT from patients with MDD (FMT-MDD) and healthy individuals (FMT-Healthy) into male Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats and assessed depressive-like behaviour. No behavioural differences were observed in the FSL rats. In FRL rats, the FMT-Healthy group displayed significantly less depressive-like behaviour than the FMT-MDD group. However, there was no difference in behaviour between FMT-MDD FRL rats and negative controls, indicating that FMT-Healthy FRL rats received beneficial bacteria. We additionally found different taxa between the FMT-MDD and the FMT-Healthy FRL rats, which could be traced to the donors. Four taxa, three belonging to the family Ruminococcaceae and the genus Lachnospira, were significantly elevated in relative abundance in FMT-MDD rats, while the genus Coprococcus was depleted. In this study, the FMT-MDD group was different from the FMT-Healthy group based on behaviour and intestinal taxa.}, }
@article {pmid34750307, year = {2022}, author = {Berding, K and Cryan, JF}, title = {Microbiota-targeted interventions for mental health.}, journal = {Current opinion in psychiatry}, volume = {35}, number = {1}, pages = {3-9}, pmid = {34750307}, issn = {1473-6578}, mesh = {*Gastrointestinal Microbiome ; Humans ; Mental Health ; *Microbiota ; Prebiotics ; *Synbiotics ; }, abstract = {PURPOSE OF REVIEW: The gut microbiota has emerged as a key conduit in mental health and is a promising target for interventions. This review provides an update on recent advances in using microbiota-targeted approaches for the management of mental health.<br><br>RECENT FINDINGS: Approaches that have emerged as microbiota-targeted interventions in the management of mental health include probiotics, prebiotics, synbiotics, fecal microbiota transplant as well as diet. Among these approaches, probiotic supplementation has been investigated most prominently, providing promising evidence for its use in improving mood and anxiety. There is also growing interest in the use of multistrain probiotics, whole dietary interventions or combined approaches, with encouraging results emerging from recent studies.<br><br>SUMMARY: Although the current literature preliminarily supports targeting the microbiota to manage mental health and use as adjuvant therapies for certain brain disorders, large gaps remain and especially data including clinical cohorts remains scarce. Research studies including larger cohorts, well-characterized clinical populations and defined duration and dosage of the intervention are required to develop evidence-based guidelines for microbiota-targeted strategies.}, }
@article {pmid34747338, year = {2021}, author = {van der Vossen, EWJ and Bastos, D and Stols-Gonçalves, D and de Goffau, MC and Davids, M and Pereira, JPB and Li Yim, AYF and Henneman, P and Netea, MG and de Vos, WM and de Jonge, W and Groen, AK and Nieuwdorp, M and Levin, E}, title = {Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1993513}, pmid = {34747338}, issn = {1949-0984}, mesh = {Adult ; Aged ; DNA Methylation ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Insulin Resistance ; Male ; Metabolic Syndrome/genetics/metabolism/microbiology/*therapy ; Microfilament Proteins/genetics/metabolism ; Middle Aged ; Young Adult ; }, abstract = {Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the pathophysiology of insulin resistance. Despite these developments, there is still a limited understanding of the multitude of effects associated with FMT on the general physiology of the host, beyond changes in gut microbiome composition. We examined the effect of either allogenic (lean donor) or autologous FMTs on the gut microbiome, plasma metabolome, and epigenomic (DNA methylation) reprogramming in peripheral blood mononuclear cells in individuals with metabolic syndrome measured at baseline (pre-FMT) and after 6 weeks (post-FMT). Insulin sensitivity was determined with a stable isotope-based 2 step hyperinsulinemic clamp and multivariate machine learning methodology was used to uncover discriminative microbes, metabolites, and DNA methylation loci. A larger gut microbiota shift was associated with an allogenic than with autologous FMT. Furthemore, the data results of the the allogenic FMT group data indicates that the introduction of new species can potentially modulate the plasma metabolome and (as a result) the epigenome. Most notably, the introduction of Prevotella ASVs directly correlated with methylation of AFAP1, a gene involved in mitochondrial function, insulin sensitivity, and peripheral insulin resistance (Rd, rate of glucose disappearance). FMT was found to have notable effects on the gut microbiome but also on the host plasma metabolome and the epigenome of immune cells providing new avenues of inquiry in the context of metabolic syndrome treatment for the manipulation of host physiology to achieve improved insulin sensitivity.}, }
@article {pmid34746183, year = {2021}, author = {Yang, B and Tian, H and Ye, C and Lin, Z and Zhao, D and Ma, C and Zhao, J and Wu, S and Jiang, R and Li, N and Qin, H and Chen, Q}, title = {The Efficacy and Safety of Fecal Microbiota Transplantation Combined With Biofeedback for Mixed Constipation: A Retrospective Cohort Study.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {746990}, pmid = {34746183}, issn = {2296-858X}, abstract = {This study aims to assess the effectiveness and safety of fecal microbiota transplantation (FMT) combined with biofeedback for patients with mixed constipation. Patients who received biofeedback (biofeedback group, n = 40) and those who received FMT combined with biofeedback (FMT combination group, n = 45) were enrolled. Spontaneous bowel movements (SBMs) frequency, Bristol Stool Form Scale (BSFS), and Patient Assessment of Constipation Symptoms (PAC-SYM) score were analyzed to evaluate the effect of treatment. Gastrointestinal Quality of Life Index (GIQLI) scores of patients were used to assess the quality of life, and the safety of FMT combination therapy was evaluated by the presence of adverse events. The 16S rRNA gene sequencing was performed on the fecal samples of 12 donors, feces of 31 patients before and after receiving FMT combination treatment. Comparing the biofeedback group and the FMT combination group 1 month after the treatment, significant differences were observed in the mean value of SBM frequency, BSFS, and PAC-SYM scores, which were 2.15 ± 1.05 vs. 3.61 ± 0.89 (p = 0.0031), 2.1 ± 0.9 vs. 2.5 ± 1.2 (p = 0.008), and 2.4 ± 0.5 vs. 2.2 ± 0.6 (p = 0.0021), respectively. Meanwhile, FMT combination therapy had long-term beneficial effects according to the data collected at six months and 12 months after the treatment. With respect to the quality of life, GIQLI scores were higher in the FMT combination group (103.6 ± 15.1) compared with that in the biofeedback group (88.7 ± 10.1) one month after administration (p = 0.0042). In addition, there were no significant differences between the two groups in adverse events, including abdominal pain, diarrhea, dizziness, nausea, vomiting, and other side effects. Results of 16S rRNA gene sequencing showing some well-known probiotics had significantly increased after FMT combination treatment compared with pre-FMT samples, such as Prevotella and Bifidobacterium. Findings of this study suggested that FMT combined with biofeedback could be effective and safe for patients with mixed constipation.}, }
@article {pmid34746161, year = {2021}, author = {Xiang, L and Yu, Y and Ding, X and Zhang, H and Wen, Q and Cui, B and Zhang, F}, title = {Exclusive Enteral Nutrition Plus Immediate vs. Delayed Washed Microbiota Transplantation in Crohn's Disease With Malnutrition: A Randomized Pilot Study.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {666062}, pmid = {34746161}, issn = {2296-858X}, abstract = {Background: The potential of washed microbiota transplantation (WMT) in Crohn's disease (CD) has been reported. This study aimed to explore the suitable timing of WMT in patients with CD complicated with malnutrition. Methods: This is a randomized, open-label study. Patients with active CD complicated with malnutrition were included and 1:1 randomized to undergo WMT at day 1 (group WMT-DAY1) or day 8 (group WMT-DAY8). The observation duration was 15 days. Exclusive enteral nutrition (EEN) was administered in both groups. The primary outcome was the improvement in nutritional parameters at day 8 and day 15 in two groups. The secondary outcome was the rate of clinical remission at day 15 in two groups. Results: Totally 19 patients completed the trial. At day 8, the lymphocyte count, albumin and prealbumin increased significantly compared to those at day 1 in group WMT-DAY1 (p = 0.018, p = 0.028, p = 0.028, respectively), while no significant increase in any nutritional parameter was shown in group WMT-DAY8. At day 15, albumin increased significantly compared to that at day 1 in both groups (p < 0.05), while significant increase in prealbumin was only shown in group WMT-DAY1 (p = 0.004) compared to that at day 1. The rate of clinical remission at day 15 in group WMT-DAY1 and group WMT-DAY8 was 87.5% (7/8) and 72.7% (8/11), respectively (p = 0.603). Conclusion: EEN combined with immediate WMT intervention could rapidly improve the nutritional status and induce clinical remission in malnourished patients with CD. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02897661.}, }
@article {pmid34746023, year = {2021}, author = {Liu, J and Gu, L and Zhang, M and Zhang, S and Wang, M and Long, Y and Zhang, X}, title = {The Fecal Microbiota Transplantation: A Remarkable Clinical Therapy for Slow Transit Constipation in Future.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {732474}, pmid = {34746023}, issn = {2235-2988}, mesh = {Bacteria ; *Constipation/therapy ; *Fecal Microbiota Transplantation ; Humans ; }, abstract = {Slow transit constipation is a common condition that would be difficult to treat in clinical practice with a widespread incidence in the population. Pharmacotherapy and surgery are common treatment modalities. However, the clinical effect is limited, and patients still suffer from it. As the researchers strived in this field for decades, the profound relationship between slow transit constipation and fecal microbiota transplantation has comprehensively been sustained. It is very pivotal to maintain intestinal homeostasis, the structure function and metabolic function of symbiotic bacteria, which can inhibit the engraftment of intestinal pathogens. This mini review explains the treatment effects and possible mechanisms of the fecal microbiota transplantation in treating slow transit constipation. Simultaneously, it is found that there is significant improvement in the disease by adjusting the intestinal microbes like fecal microbiota transplantation. Fecal microbiota transplantation has efficient therapeutic effects in slow transit constipation compared with traditional therapies.}, }
@article {pmid34745944, year = {2021}, author = {Alexander, T and Snowden, JA and Burman, J and Chang, HD and Del Papa, N and Farge, D and Lindsay, JO and Malard, F and Muraro, PA and Nitti, R and Salas, A and Sharrack, B and Mohty, M and Greco, R}, title = {Intestinal Microbiome in Hematopoietic Stem Cell Transplantation For Autoimmune Diseases: Considerations and Perspectives on Behalf of Autoimmune Diseases Working Party (ADWP) of the EBMT.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {722436}, pmid = {34745944}, issn = {2234-943X}, abstract = {Over the past decades, hematopoietic stem cell transplantation (HSCT) has been evolving as specific treatment for patients with severe and refractory autoimmune diseases (ADs), where mechanistic studies have provided evidence for a profound immune renewal facilitating the observed beneficial responses. The intestinal microbiome plays an important role in host physiology including shaping the immune repertoire. The relationships between intestinal microbiota composition and outcomes after HSCT for hematologic diseases have been identified, particularly for predicting the mortality from infectious and non-infectious causes. Furthermore, therapeutic manipulations of the gut microbiota, such as fecal microbiota transplant (FMT), have emerged as promising therapeutic approaches for restoring the functional and anatomical integrity of the intestinal microbiota post-transplantation. Although changes in the intestinal microbiome have been linked to various ADs, studies investigating the effect of intestinal dysbiosis on HSCT outcomes for ADs are scarce and require further attention. Herein, we describe some of the landmark microbiome studies in HSCT recipients and patients with chronic ADs, and discuss the challenges and opportunities of microbiome research for diagnostic and therapeutic purposes in the context of HSCT for ADs.}, }
@article {pmid34744165, year = {2021}, author = {Liu, Y and Wang, H and Gui, S and Zeng, B and Pu, J and Zheng, P and Zeng, L and Luo, Y and Wu, Y and Zhou, C and Song, J and Ji, P and Wei, H and Xie, P}, title = {Proteomics analysis of the gut-brain axis in a gut microbiota-dysbiosis model of depression.}, journal = {Translational psychiatry}, volume = {11}, number = {1}, pages = {568}, pmid = {34744165}, issn = {2158-3188}, mesh = {Animals ; Behavior, Animal ; Brain-Gut Axis ; Depression ; *Depressive Disorder, Major ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Mice ; Proteomics ; }, abstract = {Major depressive disorder (MDD) is a serious mental illness. Increasing evidence from both animal and human studies suggested that the gut microbiota might be involved in the onset of depression via the gut-brain axis. However, the mechanism in depression remains unclear. To explore the protein changes of the gut-brain axis modulated by gut microbiota, germ-free mice were transplanted with gut microbiota from MDD patients to induce depression-like behaviors. Behavioral tests were performed following fecal microbiota transplantation. A quantitative proteomics approach was used to examine changes in protein expression in the prefrontal cortex (PFC), liver, cecum, and serum. Then differential protein analysis and weighted gene coexpression network analysis were used to identify microbiota-related protein modules. Our results suggested that gut microbiota induced the alteration of protein expression levels in multiple tissues of the gut-brain axis in mice with depression-like phenotype, and these changes of the PFC and liver were model specific compared to chronic stress models. Gene ontology enrichment analysis revealed that the protein changes of the gut-brain axis were involved in a variety of biological functions, including metabolic process and inflammatory response, in which energy metabolism is the core change of the protein network. Our data provide clues for future studies in the gut-brain axis on protein level and deepen the understanding of how gut microbiota cause depression-like behaviors.}, }
@article {pmid34744033, year = {2022}, author = {Bernuth, S and Jakubietz, M and Isbert, C and Reibetanz, J and Meffert, R and Jakubietz, R and Schmidt, K}, title = {Central perforated VRAM flap and neurostimulated levator augmentation for functional and aesthetical reconstruction after abdominoperineal excision in cancer.}, journal = {Technology and health care : official journal of the European Society for Engineering and Medicine}, volume = {30}, number = {4}, pages = {815-825}, doi = {10.3233/THC-213021}, pmid = {34744033}, issn = {1878-7401}, mesh = {Humans ; *Myocutaneous Flap/transplantation ; Postoperative Complications ; *Proctectomy ; Quality of Life ; *Plastic Surgery Procedures/methods ; *Rectal Neoplasms/surgery ; Rectus Abdominis/surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: Preservation of quality of life regarding fecal continence after abdominoperineal excision (APE) in cancer is challenging. Simultaneous soft tissue coverage and restoration of continence mechanism can be provided through an interdisciplinary collaboration of colorectal and plastic reconstructive surgery.<br><br>OBJECTIVE: Evaluation of surgical procedure and outcome combining soft tissue reconstruction using a central perforated vertical rectus abdominis myocutaneous flap (VRAM), implementing a perineostoma and restoring anorectal angle augmenting the levator ani by neurostimulated graciloplasty.<br><br>METHODS: 14 Patients underwent APE due to cancer. In all patients coverage was achieved by pedicled VRAM and simultaneous pull-through descendostomy (perineostoma). 10 of those patients received a levator augmentation additionally. Postoperative complications, functional measures of continence as well as quality of life were obtained.<br><br>RESULTS: Perineal minor complication rate was 43% without need of surgical intervention. All but one VRAM survived. Continence measures and disease specific life quality showed a good preservation of continence in most patients.<br><br>CONCLUSION: The results present a complex therapy option accomplished by a collaboration of two highly specialized partners (visceral and plastic surgery) after total loss of the sphincter function and consecutive fecal insufficiency after APE.}, }
@article {pmid34743650, year = {2021}, author = {Bajaj, JS and Shamsaddini, A and Acharya, C and Fagan, A and Sikaroodi, M and Gavis, E and McGeorge, S and Khoruts, A and Fuchs, M and Sterling, RK and Lee, H and Gillevet, PM}, title = {Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1993584}, pmid = {34743650}, issn = {1949-0984}, support = {I01 CX001076/CX/CSRD VA/United States ; R01 HS025412/HS/AHRQ HHS/United States ; R21 TR003095/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/genetics ; *Bacterial Adhesion ; Bacterial Physiological Phenomena ; Bacterial Proteins/genetics/*metabolism ; *Biofilms ; Cohort Studies ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis/*microbiology/therapy ; Male ; Middle Aged ; Virulence Factors/genetics/*metabolism ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: Altered gut microbiota is associated with poor outcomes in cirrhosis, including infections and hepatic encephalopathy (HE). However, the role of bacterial virulence factors (VFs) is unclear. Aim: Define association of VFs with cirrhosis severity and infections, their linkage with outcomes, and impact of fecal microbiota transplant (FMT).<br><br>METHODS: VF abundances were determined using metagenomic analysis in stools from controls and cirrhosis patients (compensated, HE-only, ascites-only, both and infected). Patients were followed for 90-day hospitalizations and 1-year death. Stool samples collected before/after a placebo-controlled FMT trial were also analyzed. Bacterial species and VFs for all species and selected pathogens (Escherichia, Klebsiella, Pseudomonas, Staphylococcus, Streptococcus, and Enterococcus spp) were compared between groups. Multi-variable analyses were performed for clinical biomarkers and VFs for outcome prediction. Changes in VFs pre/post-FMT and post-FMT/placebo were analyzed. Results: We included 233 subjects (40 controls, 43 compensated, 30 HE-only, 20 ascites-only, 70 both, and 30 infected). Decompensated patients, especially those with infections, had higher VFs coding for siderophores, biofilms, and adhesion factors versus the rest. Biofilm and adhesion VFs from Enterobacteriaceae and Enterococcus spp associated with death and hospitalizations independent of clinical factors regardless of when all VFs or selected pathogens were analyzed. FMT was associated with reduced VF post-FMT versus pre-FMT and post-placebo groups.<br><br>CONCLUSIONS: Virulence factors from multiple species focused on adhesion and biofilms increased with decompensation and infections, associated with death and hospitalizations independent of clinical factors, and were attenuated with FMT. Strategies focused on targeting multiple virulence factors could potentially impact outcomes in cirrhosis.<br><br>PRESENTATIONS: Portions of this manuscript were an oral presentation in the virtual International Liver Congress 2021.<br><br>ABBREVIATIONS: VF: virulence factors, HE: hepatic encephalopathy, FMT: Fecal microbiota transplant, PPI: proton pump inhibitors, LPS: lipopolysaccharides, VFDB: Virulence factor database, OTU: operational taxonomic units, SBP: spontaneous bacterial peritonitis, UTI: urinary tract infections, MRSA: methicillin resistant Staphylococcus aureus, VRE: vancomycin-resistant Enterococcus, MAAsLin2: Microbiome Multivariable Associations with Linear Models, LPS: lipopolysaccharides, AKI: acute kidney injury.}, }
@article {pmid34737978, year = {2021}, author = {Li, N and Chen, H and Cheng, Y and Xu, F and Ruan, G and Ying, S and Tang, W and Chen, L and Chen, M and Lv, L and Ping, Y and Chen, D and Wei, Y}, title = {Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {759435}, pmid = {34737978}, issn = {2235-2988}, mesh = {*Autism Spectrum Disorder/therapy ; *Autistic Disorder ; Child ; Eubacterium ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Autism spectrum disorder (ASD) is a severe brain development disorder that is characterized by deficits in social communication and restricted, repetitive and stereotyped behaviors. Accumulating evidence has suggested that gut microbiota disorders play important roles in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients. Manipulation of the gut microbiota by fecal microbiota transplantation (FMT) was recently shown to be a promising therapy for the treatment of various diseases. Here, we performed a clinical trial to evaluate the effect of FMT on gastrointestinal (GI) and ASD symptoms and gut microbiota alterations in children with ASD. We found that there was a large difference in baseline characteristics of behavior, GI symptoms, and gut microbiota between children with ASD and typically developing (TD) control children. FMT could improve GI symptoms and ASD symptoms without inducing any severe complications. Similarly, FMT significantly changed the serum levels of neurotransmitters. We further observed that FMT could promote the colonization of donor microbes and shift the bacterial community of children with ASD toward that of TD controls. The abundance of Eubacterium coprostanoligenes pre-FMT was positively correlated with high GSRS scores, whereas a decrease in Eubacterium coprostanoligenes abundance induced by FMT was associated with the FMT response. Our data suggest that FMT might be a promising therapeutic strategy to improve the GI and behavioral symptoms of patients with ASD, possibly due to its ability to alter gut microbiota and highlight a specific microbiota intervention that targets Eubacterium coprostanoligenes that can enhance the FMT response. This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (trial registration number ChiCTR1800014745).}, }
@article {pmid34737977, year = {2021}, author = {Genton, L and Lazarevic, V and Stojanovic, O and Spiljar, M and Djaafar, S and Koessler, T and Dutoit, V and Gaïa, N and Mareschal, J and Macpherson, AJ and Herrmann, F and Trajkovski, M and Schrenzel, J}, title = {Metataxonomic and Metabolic Impact of Fecal Microbiota Transplantation From Patients With Pancreatic Cancer Into Germ-Free Mice: A Pilot Study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {752889}, pmid = {34737977}, issn = {2235-2988}, mesh = {Animals ; Bacteroidetes ; Clostridiales ; *Fecal Microbiota Transplantation ; Humans ; Mice ; *Pancreatic Neoplasms ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; Veillonellaceae ; }, abstract = {BACKGROUND: Body weight (BW) loss is prevalent in patients with pancreatic cancer (PC). Gut microbiota affects BW and is known to directly shape the host immune responses and antitumor immunity. This pilot study evaluated the link between gut microbiota, metabolic parameters and inflammatory/immune parameters, through the fecal material transplantation (FMT) of PC patients and healthy volunteers into germ-free (GF) mice.<br><br>METHODS: We transplanted the feces from five PC patients and five age- and gender-matched healthy volunteers into two GF mice each. Mouse BW and energy intake were measured every 1-5 days, oral glucose on day 21, insulin tolerance on day 26, fecal bacterial taxonomic profile by 16S rRNA gene sequencing on day 5, 10, 15 and 30, and gut-associated lymphoid tissue T cells, plasma cytokines and weights of fat and muscle mass at sacrifice (day 34). Results are presented as mean &#xb1; SD. The continuous parameters of mice groups were compared by linear univariate regressions, and their bacterial communities by Principal Coordinates Analysis (PCoA), Bray-Curtis similarity and ANCOM test.<br><br>RESULTS: Recipients of feces from PC patients and healthy volunteers had similar BW gain and food intake. Visceral fat was lower in recipients of feces from PC patients than from healthy individuals (0.72 &#xb1; 0.17 vs. 0.92 &#xb1; 0.14&#xa0;g; coeff -0.19, 95% CI -0.38, -0.02, p=0.035). The other non-metataxonomic parameters did not differ between groups. In PCoA, microbiota from PC patients clustered apart from those of healthy volunteers and the same pattern was observed in transplanted mice. The proportions of Clostridium bolteae, Clostridium scindens, Clostridium_g24_unclassified and Phascolarctobacterium faecium were higher, while those of Alistipes obesi, Lachnospiraceae PAC000196_s and Coriobacteriaceae_unclassified species were lower in PC patients and in mice transplanted with the feces from these patients.<br><br>CONCLUSION: In this pilot study, FMT from PC patients was associated with a decrease in visceral fat as compared to FMT from healthy individuals. Some of the differences in fecal microbiota between PC and control samples are common to humans and mice. Further research is required to confirm that feces contain elements involved in metabolic and immune alterations.}, }
@article {pmid34737725, year = {2021}, author = {Arora, T and Tremaroli, V}, title = {Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {761834}, pmid = {34737725}, issn = {1664-2392}, mesh = {Animals ; Bacteria/metabolism ; Butyrates/*pharmacology ; Diabetes Mellitus, Type 2/*drug therapy ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects ; Humans ; }, abstract = {Metagenomics studies have shown that type 2 diabetes (T2D) is associated with an altered gut microbiota. Whereas different microbiota patterns have been observed in independent human cohorts, reduction of butyrate-producing bacteria has consistently been found in individuals with T2D, as well as in those with prediabetes. Butyrate is produced in the large intestine by microbial fermentations, particularly of dietary fiber, and serves as primary fuel for colonocytes. It also acts as histone deacetylase inhibitor and ligand to G-protein coupled receptors, affecting cellular signaling in target cells, such as enteroendocrine cells. Therefore, butyrate has become an attractive drug target for T2D, and treatment strategies have been devised to increase its intestinal levels, for example by supplementation of butyrate-producing bacteria and dietary fiber, or through fecal microbiota transplant (FMT). In this review, we provide an overview of current literature indicating that these strategies have yielded encouraging results and short-term benefits in humans, but long-term improvements of glycemic control have not been reported so far. Further studies are required to find effective approaches to restore butyrate-producing bacteria and butyrate levels in the human gut, and to investigate their impact on glucose regulation in T2D.}, }
@article {pmid34735024, year = {2022}, author = {Waller, KMJ and Leong, RW and Paramsothy, S}, title = {An update on fecal microbiota transplantation for the treatment of gastrointestinal diseases.}, journal = {Journal of gastroenterology and hepatology}, volume = {37}, number = {2}, pages = {246-255}, doi = {10.1111/jgh.15731}, pmid = {34735024}, issn = {1440-1746}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Diseases/therapy ; Humans ; Treatment Outcome ; }, abstract = {Our understanding of the microbiome and its implications for human health and disease continues to develop. Fecal microbiota transplantation (FMT) is now an established treatment for recurrent Clostridioides difficile infection. There is also increasing evidence for the efficacy of FMT in inducing remission for mild-moderate ulcerative colitis. However, for other indications, data for FMT are limited, with randomized controlled trials rare, typically small and often conflicting. Studies are continuing to explore the role of FMT for many other conditions, including Crohn's disease, functional gut disorders, metabolic syndrome, modulating responses to chemotherapy, eradication of multidrug resistant organisms, and the gut-brain axis. In light of safety, logistical, and regulatory challenges, there is a move to standardized products including narrow spectrum consortia. However, the mechanisms underpinning FMT remain incompletely understood, including the role of non-bacterial components, which may limit success of novel microbial approaches.}, }
@article {pmid34734433, year = {2022}, author = {Suk, KT and Koh, H}, title = {New perspective on fecal microbiota transplantation in liver diseases.}, journal = {Journal of gastroenterology and hepatology}, volume = {37}, number = {1}, pages = {24-33}, doi = {10.1111/jgh.15729}, pmid = {34734433}, issn = {1440-1746}, support = {//Ministry of Education, Science and Technology/ ; NRF-2020R1A6A1A03043026//National Research Foundation of Korea (NRF)/ ; NRF-2019R1I1A3A01060447//National Research Foundation of Korea (NRF)/ ; NRF-2018M3A9F3020956//National Research Foundation of Korea (NRF)/ ; }, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Liver Diseases/therapy ; }, abstract = {Chronic liver disease including non-alcoholic fatty liver disease and alcohol-related liver disease is one of the most common diseases worldwide. The gut-liver axis plays an important role in the pathogenesis of liver disease. Small intestinal bacterial overgrowth, dysbiosis, leaky bowel, bacterial translocation, and imbalanced metabolites are related to the progression of chronic liver disease. Recently, novel therapeutic approaches for microbiota modulation such as personalized diet, probiotics, prebiotics, antibiotics, engineered microbiotas, phage therapy, stomach operation, and fecal microbiota transplantation (FMT) have been proposed with numerous promising results in the effectiveness and clinical application. Although the evidence is still lacking, FMT, a type of fecal bacteriotherapy, has been known as a candidate for the treatment of liver disease. This review article focuses on the most recent advances in our understanding of FMT in chronic liver disease such as non-alcoholic and alcohol-related liver disease.}, }
@article {pmid34734369, year = {2022}, author = {An, L and Wirth, U and Koch, D and Schirren, M and Drefs, M and Koliogiannis, D and Nieß, H and Andrassy, J and Guba, M and Bazhin, AV and Werner, J and Kühn, F}, title = {The Role of Gut-Derived Lipopolysaccharides and the Intestinal Barrier in Fatty Liver Diseases.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {26}, number = {3}, pages = {671-683}, pmid = {34734369}, issn = {1873-4626}, mesh = {Dysbiosis/metabolism ; *Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides/metabolism ; Liver/pathology ; *Liver Diseases, Alcoholic/metabolism ; *Non-alcoholic Fatty Liver Disease/pathology/therapy ; }, abstract = {BACKGROUND: Hepatosteatosis is the earliest stage in the pathogenesis of nonalcoholic fatty (NAFLD) and alcoholic liver disease (ALD). As NAFLD is affecting 10-24% of the general population and approximately 70% of obese patients, it carries a large economic burden and is becoming a major reason for liver transplantation worldwide. ALD is a major cause of morbidity and mortality causing 50% of liver cirrhosis and 10% of liver cancer related death. Increasing evidence has accumulated that gut-derived factors play a crucial role in the development and progression of chronic liver diseases.<br><br>METHODS: A selective literature search was conducted in Medline and PubMed, using the terms "nonalcoholic fatty liver disease," "alcoholic liver disease," "lipopolysaccharide," "gut barrier," and "microbiome."<br><br>RESULTS: Gut dysbiosis and gut barrier dysfunction both contribute to chronic liver disease by abnormal regulation of the gut-liver axis. Thereby, gut-derived lipopolysaccharides (LPS) are a key factor in inducing the inflammatory response of liver tissue. The review further underlines that endotoxemia is observed in both NAFLD and ALD patients. LPS plays an important role in conducting liver damage through the LPS-TLR4 signaling pathway. Treatments targeting the gut microbiome and the gut barrier such as fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, and intestinal alkaline phosphatase (IAP) represent potential treatment modalities for NAFLD and ALD.<br><br>CONCLUSIONS: The gut-liver axis plays an important role in the development of liver disease. Treatments targeting the gut microbiome and the gut barrier have shown beneficial effects in attenuating liver inflammation and need to be further investigated.}, }
@article {pmid34733783, year = {2021}, author = {Zhang, W and An, Y and Qin, X and Wu, X and Wang, X and Hou, H and Song, X and Liu, T and Wang, B and Huang, X and Cao, H}, title = {Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {739648}, pmid = {34733783}, issn = {2234-943X}, abstract = {Accumulating evidence from studies in humans and animal models has elucidated that gut microbiota, acting as a complex ecosystem, contributes critically to colorectal cancer (CRC). The potential mechanisms often reported emphasize the vital role of carcinogenic activities of specific pathogens, but in fact, a series of metabolites produced from exogenous dietary substrates or endogenous host compounds occupy a decisive position similarly. Detrimental gut microbiota-derived metabolites such as trimethylamine-N-oxide, secondary bile acids, hydrogen sulfide and N-nitroso compounds could reconstruct the ecological composition and metabolic activity of intestinal microorganisms and formulate a microenvironment that opens susceptibility to carcinogenic stimuli. They are implicated in the occurrence, progression and metastasis of CRC through different mechanisms, including inducing inflammation and DNA damage, activating tumorigenic signaling pathways and regulating tumor immunity. In this review, we mainly summarized the intimate relationship between detrimental gut microbiota-derived metabolites and CRC, and updated the current knowledge about detrimental metabolites in CRC pathogenesis. Then, multiple interventions targeting these metabolites for CRC management were critically reviewed, including diet modulation, probiotics/prebiotics, fecal microbiota transplantation, as well as more precise measures such as engineered bacteria, phage therapy and chemopreventive drugs. A better understanding of the interplay between detrimental microbial metabolites and CRC would hold great promise against CRC.}, }
@article {pmid34733507, year = {2021}, author = {Sahitya, DSK and Jandiyal, A and Jain, A and Senapati, J and Nanda, S and Aggarwal, M and Kumar, P and Mohapatra, S and Ray, P and Malhotra, P and Mahapatra, M and Dhawan, R}, title = {Prevention and management of carbapenem-resistant Enterobacteriaceae in haematopoietic cell transplantation.}, journal = {Therapeutic advances in infectious disease}, volume = {8}, number = {}, pages = {20499361211053480}, pmid = {34733507}, issn = {2049-9361}, abstract = {Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high morbidity and mortality rates in haematopoietic cell transplantation (HCT) recipients. Factors like mucositis, neutropenia, prolonged hospital stay, and frequent use of prophylactic antimicrobials make HCT recipients especially susceptible to CRE infections. Low culture positivity rates, delay in microbiological diagnosis, and resistance to empirical antimicrobial therapy for febrile neutropenia are responsible for high mortality rates in HCT recipients infected with CRE. In this review we discuss the epidemiology, diagnosis, and management of CRE infections with particular emphasis on patients undergoing HCT. We emphasise the need for preventive strategies like multidisciplinary antimicrobial stewardship, and pre-emptive screening for CRE colonisation in prospective HCT patients as measures to mitigate the adverse impact of CRE on HCT outcomes. Newer diagnostic tests like polymerase chain reaction and matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) assay that enable earlier and better identification of CRE isolates are discussed. Antimicrobial agents available against CRE, including newer agents like ceftazidime-avibactam and meropenem-vaborbactam, have been reviewed. We also discuss the data on promising experimental treatments against CRE: phage therapy and healthy donor faecal microbiota transplant. Finally, this review puts forth recommendations as per existing literature on diagnosis and management of CRE infections in blood and marrow transplant (BMT) unit.}, }
@article {pmid34731398, year = {2022}, author = {Davrandi, M and Harris, S and Smith, PJ and Murray, CD and Lowe, DM}, title = {The Relationship Between Mucosal Microbiota, Colitis, and Systemic Inflammation in Chronic Granulomatous Disorder.}, journal = {Journal of clinical immunology}, volume = {42}, number = {2}, pages = {312-324}, pmid = {34731398}, issn = {1573-2592}, mesh = {*Colitis/etiology/metabolism ; *Granulomatous Disease, Chronic/complications/diagnosis ; Humans ; Inflammation/complications ; *Microbiota ; Mucous Membrane/metabolism/pathology ; }, abstract = {PURPOSE: Chronic granulomatous disorder (CGD) is a primary immunodeficiency which is frequently complicated by inflammatory colitis and is associated with systemic inflammation. Herein, we aimed to investigate the role of the microbiome in the pathogenesis of colitis and systemic inflammation.<br><br>METHODS: We performed 16S rDNA sequencing on mucosal biopsy samples from each segment of 10 CGD patients' colons and conducted compositional and functional pathway prediction analyses.<br><br>RESULTS: The microbiota in samples from colitis patients demonstrated reduced taxonomic alpha-diversity compared to unaffected patients, even in apparently normal bowel segments. Functional pathway richness was similar between the colitic and non-colitic mucosa, although metabolic pathways involved in butyrate biosynthesis or utilization were enriched in patients with colitis and correlated positively with fecal calprotectin levels. One patient with very severe colitis was dominated by Enterococcus spp., while among other patients Bacteroides spp. abundance correlated with colitis severity measured by fecal calprotectin and an endoscopic severity score. In contrast, Blautia abundance is associated with low severity scores and mucosal health. Several taxa and functional pathways correlated with concentrations of inflammatory cytokines in blood but not with colitis severity. Notably, dividing patients into "high" and "low" systemic inflammation groups demonstrated clearer separation than on the basis of colitis status in beta-diversity analyses.<br><br>CONCLUSION: The microbiome is abnormal in CGD-associated colitis and altered functional characteristics probably contribute to pathogenesis. Furthermore, the relationship between the mucosal microbiome and systemic inflammation, independent of colitis status, implies that the microbiome in CGD can influence the inflammatory phenotype of the condition.}, }
@article {pmid34724447, year = {2022}, author = {Kellermayer, R and Wu, Q and Nagy-Szakal, D and Queliza, K and Ihekweazu, FD and Bocchini, CE and Magee, AR and Oezguen, N and Spinler, JK and Hollister, EB and Shulman, RJ and Versalovic, J and Luna, RA and Savidge, TC}, title = {Fecal Microbiota Transplantation Commonly Failed in Children With Co-Morbidities.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {74}, number = {2}, pages = {227-235}, pmid = {34724447}, issn = {1536-4801}, support = {R01 AI100914/AI/NIAID NIH HHS/United States ; T32 DK007664/DK/NIDDK NIH HHS/United States ; R21 DK096323/DK/NIDDK NIH HHS/United States ; P01 AI152999/AI/NIAID NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; K24 AI121296/AI/NIAID NIH HHS/United States ; }, mesh = {Child ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Feces ; Humans ; Morbidity ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Recurrence ; Treatment Outcome ; }, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is arguably the most effective treatment for recurrent Clostridioides difficile infection (rCDI). Clinical reports on pediatric FMT have not systematically evaluated microbiome restoration in patients with co-morbidities. Here, we determined whether FMT recipient age and underlying co-morbidity influenced clinical outcomes and microbiome restoration when treated from shared fecal donor sources.<br><br>METHODS: Eighteen rCDI patients participating in a single-center, open-label prospective cohort study received fecal preparation from a self-designated (single case) or two universal donors. Twelve age-matched healthy children and four pediatric ulcerative colitis (UC) cases from an independent serial FMT trial, but with a shared fecal donor were examined as controls for microbiome restoration using 16S rRNA gene sequencing of longitudinal fecal specimens.<br><br>RESULTS: FMT was significantly more effective in rCDI recipients without underlying chronic co-morbidities where fecal microbiome composition in post-transplant responders was restored to levels of healthy children. Microbiome reconstitution was not associated with symptomatic resolution in some rCDI patients who had co-morbidities. Significant elevation in Bacteroidaceae, Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae, and Erysipelotrichaceae was consistently observed in pediatric rCDI responders, while Enterobacteriaceae decreased, correlating with augmented complex carbohydrate degradation capacity.<br><br>CONCLUSION: Recipient background disease was a significant risk factor influencing FMT outcomes. Special attention should be taken when considering FMT for pediatric rCDI patients with underlying co-morbidities.}, }
@article {pmid34722332, year = {2021}, author = {Chen, T and Wang, R and Duan, Z and Yuan, X and Ding, Y and Feng, Z and Bu, F and Liu, L and Wang, Q and Zhou, J and Zhu, L and Ni, Q and Shi, G and Chen, Y}, title = {Akkermansia muciniphila Protects Against Psychological Disorder-Induced Gut Microbiota-Mediated Colonic Mucosal Barrier Damage and Aggravation of Colitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {723856}, pmid = {34722332}, issn = {2235-2988}, mesh = {Akkermansia ; Animals ; *Colitis ; *Gastrointestinal Microbiome ; Humans ; Mice ; Verrucomicrobia ; }, abstract = {Psychological disorders are associated with increased risk of severe inflammatory bowel disease (IBD) by causing gut microbiota dysbiosis and colonic mucosal barrier damage. However, the interaction between chronic restraint stress (CRS), gut microbiota composition, and colonic mucus remains unclear. We demonstrated that mice under CRS conditions exhibited alterations in microbiota composition, disruption of colonic mucus, and aggravation of colitis. In addition, the abundance of Akkermansia muciniphila was significantly decreased in mice under CRS and UC patients with depression, and positively associated with the expression of MUC2. After antibiotic treatment, the recipient mice colonized with CRS microbiota showed barrier defects and severe colitis. Administration of Akkermansia muciniphila was found to restore colonic mucus and modify the gut microbiota. We confirm that CRS-mediated gut microbiota dysbiosis results in colonic mucosal barrier damage and aggravation of colitis. Our results suggest that A. muciniphila is expected to be a potential probiotic to protect and treat colonic mucus that is involved in IBD with psychological disorders.}, }
@article {pmid34721980, year = {2021}, author = {Ma, S and Wang, N and Zhang, P and Wu, W and Fu, L}, title = {Fecal microbiota transplantation mitigates bone loss by improving gut microbiome composition and gut barrier function in aged rats.}, journal = {PeerJ}, volume = {9}, number = {}, pages = {e12293}, pmid = {34721980}, issn = {2167-8359}, abstract = {BACKGROUND: Gut microbiota (GM) dysbiosis is closely related to bone loss and the occurrence of osteoporosis in animals and human. However, little is known about the effect and the mechanisms of fecal microbiota transplantation (FMT) on bone in the treatment of senile osteoporosis.<br><br>METHODS: Aged female rats were randomly divided into the FMT group and the control group. 3-month-old female rats were used as fecal donors. The rats were sacrificed at 12 and 24 weeks following transplantation and the serum, intestine, bone, and feces were collected for subsequent analyses.<br><br>RESULTS: The bone turnover markers of osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), and carboxy-terminal peptide (CTX) decreased significantly at 12 and 24 weeks following FMT (P < 0.05). At 12 weeks following transplantation, histomorphometric parameters including the bone volume (BV), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) of the FMT group were comparable to the control group. However, at 24 weeks following transplantation, these parameters of the FMT group were significantly higher than those of the control group (P < 0.05). Besides, the GM aggregated at 12 and 24 weeks following FMT, and the ecological distance was close between the rats in the FMT group and the donor rats. Alpha diversity, shown by the Shannon index and Simpson index, and the Firmicutes/Bacteroidetes ratio decreased significantly after FMT at 24 weeks. Furthermore, FMT restored the GM composition in aged rats at the phylum and family level, and the intestinal microbiota of the aged rats was similar to that of the donor rats. Correlation network analysis indirectly suggested the causality of FMT on alleviating osteoporosis. FMT improved the intestinal structure and up-regulated the expression of tight junction proteins of occludin, claudin, and ZO-1, which might be associated with the protective effects of FMT on bone.<br><br>CONCLUSIONS: GM transplanted from young rats alleviated bone loss in aged rats with senile osteoporosis by improving gut microbiome composition and intestinal barrier function. These data might provide a scientific basis for future clinical treatment of osteoporosis through FMT.}, }
@article {pmid34721757, year = {2021}, author = {Hong, MK and Liu, HH and Chen, GH and Zhu, JQ and Zheng, SY and Zhao, D and Diao, J and Jia, H and Zhang, DD and Chen, SX and Gao, L and Li, J}, title = {Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury.}, journal = {Oxidative medicine and cellular longevity}, volume = {2021}, number = {}, pages = {3259238}, pmid = {34721757}, issn = {1942-0994}, mesh = {Acetaminophen ; Animals ; Bacteroides/*drug effects/genetics/metabolism ; Chemical and Drug Induced Liver Injury/metabolism/microbiology/pathology/*prevention &amp; control ; Disease Models, Animal ; Diterpenes, Kaurane/*pharmacology ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Liver/*drug effects/metabolism ; Male ; Metabolome ; Mice, Inbred C57BL ; Mice, Knockout ; NF-E2-Related Factor 2/genetics/metabolism ; Urea/*metabolism ; Mice ; }, abstract = {Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Oridonin (OD), which is the major active ingredient of the traditional Chinese medicine Rabdosia rubescens, reportedly exerts anti-inflammatory and antioxidative effects. Here, we first find that OD protects against APAP-induced hepatotoxicity. The results of hepatic tissue-associated RNA-seq and metabolomics showed that the protective effects of OD were dependent upon urea cycle regulation. And such regulation of OD is gut microbiota partly dependent, as demonstrated by fecal microbiota transplantation (FMT). Furthermore, using 16S rRNA sequencing, we determined that OD significantly enriched intestinal Bacteroides vulgatus, which activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to regulate redox homeostasis against APAP by urea cycle. In conclusion, our study suggests that the Bacteroides vulgatus-urea cycle-Nrf2 axis may be a potential target for reducing APAP-induced liver injury, which is altered by OD.}, }
@article {pmid34721365, year = {2021}, author = {Zhong, Y and Cao, J and Deng, Z and Ma, Y and Liu, J and Wang, H}, title = {Effect of Fiber and Fecal Microbiota Transplantation Donor on Recipient Mice Gut Microbiota.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {757372}, pmid = {34721365}, issn = {1664-302X}, abstract = {Both fecal microbiota transplantation (FMT) and dietary fiber intervention were verified as effective ways to manipulate the gut microbiota, whereas little is known about the influence of the combined methods on gut microbiota. Here, we constructed "non-industrialized" and "industrialized" gut microbiota models to investigate the donor effect of FMT and diet effect in shaping the gut microbiota. Mice were transplanted fecal microbiota from domestic pig and received a diet with low-fiber (D) or high-fiber (DF), whereas the other two groups were transplanted fecal microbiota from wild pig and then received a diet with low-fiber (W) or high-fiber (WF), respectively. Gut microbiota of WF mice showed a lower Shannon and Simpson index (P < 0.05), whereas gut microbiota of W mice showed no significant difference than that of D and DF mice. Random forest models revealed the major differential bacteria genera between four groups, including Anaeroplasma or unclassified_o_Desulfovibrionales, which were influenced by FMT or diet intervention, respectively. Besides, we found a lower out-of-bag rate in the random forest model constructed for dietary fiber (0.086) than that for FMT (0.114). Linear discriminant analysis effective size demonstrated that FMT combined with dietary fiber altered specific gut microbiota, including Alistipes, Clostridium XIVa, Clostridium XI, and Akkermansia, in D, DF, W, and WF mice, respectively. Our results revealed that FMT from different donors coupled with dietary fiber intervention could lead to different patterns of gut microbiota composition, and dietary fiber might play a more critical role in shaping gut microbiota than FMT donor. Strategies based on dietary fiber can influence the effectiveness of FMT in the recipient.}, }
@article {pmid34718953, year = {2022}, author = {Bhattacharjee, A and Dubey, S and Sharma, S}, title = {Storage of soil microbiome for application in sustainable agriculture: prospects and challenges.}, journal = {Environmental science and pollution research international}, volume = {29}, number = {3}, pages = {3171-3183}, pmid = {34718953}, issn = {1614-7499}, support = {BT/PR27680/BCE/8/1434/2018//Department of Biotechnology , Ministry of Science and Technology/ ; PDF/2018/001905//Science and Engineering Research Board/ ; fellowship//Indian Institute of Technology Delhi/ ; }, mesh = {Agriculture ; *Microbiota ; *Soil ; Soil Microbiology ; }, abstract = {Soil microbiome is a dynamic micro-ecosystem driving and fine-tuning several biological processes in the global macro-ecosystems. Its tremendous potential towards mediating sustainability in the ecosystem necessitates the urgent need to store it optimally and efficiently as "next-generation biologicals" for future applications via soil transplantation. The challenge, therefore, is to devise a strategy for the storage of soil microbiome such that its "functionality" is preserved for later application. This review discusses the current endeavours made towards storage of the soil microbiome. The methods for assessing the integrity of soil microbiome by targeting the structural diversity and functional potential of the preserved microbiomes have also been discussed. Further, the success stories related to the storage of fecal microbiome for application in transplants have also been highlighted. This is done primarily with the objective of learning lessons, and parallel application of the knowledge gained, in bringing about improvement in the research domain of soil microbiome storage. Subsequently, the limitations of current techniques of preservation have also been delineated. Further, the open questions in the area have been critically discussed. In conclusion, possible alternatives for storage, comprehensive analyses of the composition of the stored microbiome and their potential have been presented.}, }
@article {pmid34717835, year = {2021}, author = {Gordon, AC and Gates, VL and White, SB and Harris, KR and Mouli, SK and Kim, DH and Omary, RA and Salem, R and Lewandowski, RJ and Larson, AC}, title = {Yttrium-90 Radioembolization in the VX2 Rabbit Model: Radiation Safety and Factors Influencing Delivery Efficiency.}, journal = {Journal of vascular and interventional radiology : JVIR}, volume = {32}, number = {11}, pages = {1569-1574.e11}, doi = {10.1016/j.jvir.2021.08.008}, pmid = {34717835}, issn = {1535-7732}, mesh = {Animals ; *Embolization, Therapeutic/adverse effects ; *Liver Neoplasms/radiotherapy ; Microspheres ; Rabbits ; *Radiation Exposure ; Yttrium Radioisotopes/adverse effects ; }, abstract = {The purpose of this study was to define the optimal infusion parameters and operator radiation exposure for yttrium-90 ([90]Y) radioembolization in the VX2 rabbit model of liver cancer. Forty-one rabbits with VX2 were treated with glass microspheres with vial sizes of 1, 3, and 5 GBq. The mean administered activity was 51.5 MBq (95% CI, 39.1-63.9). Delivery efficiency improved with 1 GBq versus with 3 GBq (residual 11.0% vs 46.4%, respectively; P = .0013) and improved with 1 GBq versus with 5 GBq (residual 11.0% vs 33.8%, respectively; P = .0060). The mean operator extremity exposure was 41.7 μSv/infusion. The optimal minimum infusion volume and rate was 49 mL and 21 mL/min, respectively. Fecal elimination occurred with microsphere uptake in the gallbladder at 1 and 2 weeks. [90]Y radioembolization can be safely and efficiently performed in the VX2 rabbit model. Methodological considerations as a "how-to" for the setup of a preclinical [90]Y laboratory are included to support future translational research.}, }
@article {pmid34714981, year = {2022}, author = {Nevejan, L and Mylemans, M and Vander Cruyssen, B and Stubbe, M and Van Den Bremt, S and Hofman, L and Infantino, M and Manfredi, M and Bossuyt, X and Van Hoovels, L}, title = {Pre-analytical recommendations and reference values for circulating calprotectin are sample type and assay dependent.}, journal = {Clinical chemistry and laboratory medicine}, volume = {60}, number = {2}, pages = {e57-e60}, doi = {10.1515/cclm-2021-0998}, pmid = {34714981}, issn = {1437-4331}, mesh = {*Biological Assay ; Biomarkers ; Enzyme-Linked Immunosorbent Assay ; Feces ; Humans ; *Leukocyte L1 Antigen Complex ; Reference Values ; }, }
@article {pmid34714460, year = {2022}, author = {Okuyama, Y and Okamoto, T and Sasaki, D and Ozaki, K and Songee, J and Hatakeyama, S and Mikami, T and Ohyama, C}, title = {The influence of gut microbiome on progression of overactive bladder symptoms: a community-based 3-year longitudinal study in Aomori, Japan.}, journal = {International urology and nephrology}, volume = {54}, number = {1}, pages = {9-16}, pmid = {34714460}, issn = {1573-2584}, mesh = {Adult ; Aged ; Community Health Centers ; Disease Progression ; Female ; *Gastrointestinal Microbiome ; Humans ; Japan ; Longitudinal Studies ; Male ; Middle Aged ; Streptococcus/isolation &amp; purification ; Time Factors ; Urinary Bladder, Overactive/*diagnosis/*microbiology ; }, abstract = {PURPOSE: To assess the influence of gut microbiome on overactive bladder (OAB) symptoms progression.<br><br>METHODS: This was a 3-year longitudinal study, Hirosaki in Japan. We assessed OAB symptoms and reviewed the medication records of each subject in 2016. We extracted 16S rRNA genes from fecal samples and analyzed gut microbiomes via next-generation sequencing. We evaluated the changes in urinary urgency (UU) and/or urgent urinary incontinence (UUI) from 2016 to 2019. We defined UU/UUI-progression as exacerbation of UU and/or UUI. We compared the clinical backgrounds and microbiota structure between UU/UUI-progression subjects and non-progression (controls). We assessed the impact of gut microbiome on the UU/UUI-progression via multivariate logistic regression analyses.<br><br>RESULTS: Of 669 subjects, 126 were UU/UUI-progression subjects. These subjects had a higher age and prevalence of proton pump inhibitor (PPI) use (14% vs. 5.4%, P&#x2009;=&#x2009;0.003), irritable bowel syndrome, sleep disturbance, and metabolic syndrome than those without. We found the different microbiota structures between subjects with UU/UUI-progression and those without. A higher relative abundance of genus Streptococcus (harmful bacterial genus for human health) appeared in UU/UUI-progression subjects (3.8% vs. 2.3%, P&#x2009;<&#x2009;0.001). Multivariate analysis revealed that age&#x2009;&#x2265;&#x2009;65&#xa0;years, current smoking, sleep disturbance, metabolic syndrome, and genus Streptococcus (Odds ratio: 1.05, P&#x2009;=&#x2009;0.029) were independent risk factors for UU/UUI-progression. PPI use turned to be a significant risk factor on a multivariate analysis without including genus Streptococcus.<br><br>CONCLUSIONS: Gut microbiome might be associated with a risk for OAB symptoms progression. PPI use might cause gut dysbiosis and increase this risk.}, }
@article {pmid34713851, year = {2021}, author = {Phrommas, J and Tanpowpong, P and Getsuwan, S and Lertudomphonwanit, C and Chantarogh, S and Anurathapan, U and Treepongkaruna, S}, title = {Diarrhea in pediatric recipients of solid organ or bone marrow transplants.}, journal = {Medicine}, volume = {100}, number = {43}, pages = {e27625}, pmid = {34713851}, issn = {1536-5964}, mesh = {Adolescent ; Bone Marrow Transplantation/*adverse effects ; Child ; Child, Preschool ; Diarrhea/*etiology ; Feces/cytology ; Female ; Graft vs Host Disease/pathology ; Humans ; Infant ; Kidney Transplantation/*adverse effects ; Leukocytes/cytology ; Liver Transplantation/*adverse effects ; Male ; Sex Factors ; }, abstract = {Diarrhea is common in adults after solid organ transplantation (SOT) and bone marrow transplantation (BMT), but data in children are limited. Therefore, we aimed to determine the incidence and etiology of pediatric early-onset diarrhea in post SOT and BMT.We reviewed children aged 6 months to 18 years who underwent liver transplantation, kidney transplantation or BMT between January 2015 and December 2019 with duration of diarrhea > 72 hours within the first 6 months after transplantation. Clinical data and diarrheal course were collected. Regression analyses were performed to define factors associated with the interested outcomes.Among 252 transplanted patients, 168 patients (66.6%) had 289 documented episodes of diarrhea. A diagnosis of 68.2% of post-transplant diarrhea remained 'indefinite'. Enteric infection in SOT and gastrointestinal acute graft-versus-host disease (GI-aGVHD) in BMT were the commonly identified etiologies. Among 182 episodes among BMT children, skin rash was more pronounced when compared the ones with diarrhea > 7 days vs ≤ 7 days (odds ratio [OR] 13.9; 95% CI 1.8, 107.6). Males were more likely to develop GI-aGVHD as compared to females (OR 8.9). We found that GI-aGVHD was more common in the ones with skin rash and the presence of white blood cells in stool examination (OR 8.4 and 3.1, respectively). Deaths occurred in 7.7%.Two-thirds of post-transplant children experienced at least one episode of early-onset diarrhea, of which the etiology mainly remains undefined. Various clinical factors of prolonged/chronic diarrhea and GI-aGVHD may help clinicians when managing these children.}, }
@article {pmid34712743, year = {2021}, author = {Niu, M and Chen, P}, title = {Crosstalk between gut microbiota and sepsis.}, journal = {Burns &amp; trauma}, volume = {9}, number = {}, pages = {tkab036}, pmid = {34712743}, issn = {2321-3868}, abstract = {Sepsis is an overwhelming inflammatory response to microbial infection. Sepsis management remains a clinical challenge. The role of the gut microbiome in sepsis has gained some attention. Recent evidence has demonstrated that gut microbiota regulate host physiological homeostasis mediators, including the immune system, gut barrier function and disease susceptibility pathways. Therefore, maintenance or restoration of microbiota and metabolite composition might be a therapeutic or prophylactic target against critical illness. Fecal microbiota transplantation and supplementation of probiotics are microbiota-based treatment methods that are somewhat limited in terms of evidence-based efficacy. This review focuses on the importance of the crosstalk between the gastrointestinal ecosystem and sepsis to highlight novel microbiota-targeted therapies to improve the outcomes of sepsis treatment.}, }
@article {pmid34712655, year = {2021}, author = {Zhou, J and Hou, C and Chen, H and Qin, Z and Miao, Z and Zhao, J and Wang, Q and Cui, M and Xie, C and Wang, R and Li, Q and Zuo, G and Miao, D and Jin, J}, title = {P16 [I NK 4a] Deletion Ameliorates Damage of Intestinal Epithelial Barrier and Microbial Dysbiosis in a Stress-Induced Premature Senescence Model of Bmi-1 Deficiency.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {671564}, pmid = {34712655}, issn = {2296-634X}, abstract = {This study aimed to determine whether Bmi-1 deficiency leads to intestinal epithelial barrier destruction and microbiota dysfunction, which members of the microbial community alter barrier function with age, and whether p16 [INK4a] deletion could reverse the damage of intestinal epithelial barrier and microbial dysbiosis. Intestines from Bmi-1-deficient (Bmi-1[-/-]), Bmi-1 and p16 [INK4a] double-knockout (Bmi-1[-/-]p16 [INK4a-/-]), and wild-type mice were observed for aging and inflammation. Duolink Proximity Ligation Assay, immunoprecipitation, and construction of p16 [INK4a] overexpressed adenovirus and the overexpressed plasmids of full-length, mutant, or truncated fragments for occludin were used for analyzing the interaction between p16 [INK4a] and occludin. High-throughput sequencing of V4 region amplicon of 16S ribosomal RNA was conducted using intestinal microbiota. We found Bmi-1 deficiency destructed barrier structure, barrier function, and tight junction (TJ) in intestinal epithelium; decreased the TJ proteins; increased tumor necrosis factor α (TNF-α)-dependent barrier permeability; and up-regulated proinflammatory level of macrophages induced by intestinal microbial dysbiosis. The transplantation of fecal microbiota from wild-type mice ameliorated TJ in intestinal epithelium of Bmi-1[-/-] and Bmi-1[-/-]p16 [INK4a-/-] mice. Harmful bacteria including Desulfovibrio, Helicobacter, and Oscillibacter were at a higher level in Bmi-1[-/-] mice. More harmful bacteria Desulfovibrio entered the epithelium and promoted macrophages-secreted TNF-α and caused TNF-α-dependent barrier permeability and aging. Accumulated p16 [INK4a] combined with occludin at the 1st-160th residue in cytoplasm of intestinal epithelium cells from Bmi-1[-/-] mice, which blocked formation of TJ and the repair of intestinal epithelium barrier. P16 [INK4a] deletion could maintain barrier function and microbiota balance in Bmi-1[-/-] mice through strengthening formation of TJ and decreasing macrophages-secreted TNF-α induced by Desulfovibrio entering the intestinal epithelium. Thus, Bmi-1 maintained intestinal TJ, epithelial barrier function, and microbiota balance through preventing senescence characterized by p16 [INK4a] accumulation. The clearance of p16 [INK4a] -positive cells in aging intestinal epithelium would be a new method for maintaining barrier function and microbiota balance. The residues 1-160 of occludin could be a novel therapeutic target for identifying small molecular antagonistic peptides to prevent the combination of p16 [INK4a] with occludin for protecting TJ.}, }
@article {pmid34712223, year = {2021}, author = {Lauriero, G and Abbad, L and Vacca, M and Celano, G and Chemouny, JM and Calasso, M and Berthelot, L and Gesualdo, L and De Angelis, M and Monteiro, RC}, title = {Fecal Microbiota Transplantation Modulates Renal Phenotype in the Humanized Mouse Model of IgA Nephropathy.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {694787}, pmid = {34712223}, issn = {1664-3224}, mesh = {Animals ; Antigens, CD/genetics/metabolism ; B-Cell Activating Factor/blood ; Bacteria/*metabolism ; Case-Control Studies ; Disease Models, Animal ; Dysbiosis ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Glomerulonephritis, IGA/immunology/metabolism/microbiology/*therapy ; Humans ; Immunoglobulin A/genetics/metabolism ; Kidney/immunology/metabolism/*microbiology ; Male ; Mice, Transgenic ; Phenotype ; Receptors, Fc/genetics/metabolism ; Volatile Organic Compounds/metabolism ; }, abstract = {Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. Several observations suggest that gut microbiota could be implicated in IgAN pathophysiology. Aiming at exploring whether microbiota modulation is able to influence disease outcome, we performed fecal microbiota transplantation (FMT) from healthy controls (HC-sbjs), non-progressor (NP-pts) and progressor (P-pts) IgAN patients to antibiotic-treated humanized IgAN mice (α1KI-CD89Tg), by oral gavage. FMT was able to modulate renal phenotype and inflammation. On one hand, the microbiota from P-pts was able to induce an increase of serum BAFF and galactose deficient-IgA1 levels and a decrease of CD89 cell surface expression on blood CD11b[+] cells which was associated with soluble CD89 and IgA1 mesangial deposits. On the other hand, the microbiota from HC-sbjs was able to induce a reduction of albuminuria immediately after gavage, an increased cell surface expression of CD89 on blood CD11b[+] cells and a decreased expression of KC chemokine in kidney. Higher serum BAFF levels were found in mice subjected to FMT from IgAN patients. The main bacterial phyla composition and volatile organic compounds profile significantly differed in mouse gut microbiota. Microbiota modulation by FMT influences IgAN phenotype opening new avenues for therapeutic approaches in IgAN.}, }
@article {pmid34711461, year = {2022}, author = {Lythgoe, MP and Ghani, R and Mullish, BH and Marchesi, JR and Krell, J}, title = {The potential of fecal microbiota transplantation in oncology.}, journal = {Trends in microbiology}, volume = {30}, number = {1}, pages = {10-12}, doi = {10.1016/j.tim.2021.10.003}, pmid = {34711461}, issn = {1878-4380}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; *Neoplasms/therapy ; Treatment Outcome ; }, abstract = {Immune checkpoint inhibitors (ICPIs) are efficacious treatments for several cancers. However, most patients fail to demonstrate durable complete responses. The gut microbiome composition influences the ICPI response. Two recent proof-of-concept studies have demonstrated the utility of fecal microbiota transplantation to transform ICPI responsiveness in refractory patients, providing intriguing evidence for the future of microbiota modulation within oncology.}, }
@article {pmid34711288, year = {2021}, author = {Jardou, M and Provost, Q and Brossier, C and Pinault, &#xc9; and Sauvage, FL and Lawson, R}, title = {Alteration of the gut microbiome in mycophenolate-induced enteropathy: impacts on the profile of short-chain fatty acids in a mouse model.}, journal = {BMC pharmacology &amp; toxicology}, volume = {22}, number = {1}, pages = {66}, pmid = {34711288}, issn = {2050-6511}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Colon/drug effects/pathology ; Disease Models, Animal ; Fatty Acids, Volatile/*blood ; Feces/chemistry ; Female ; Gastrointestinal Microbiome/*drug effects ; Immunosuppressive Agents/*adverse effects ; Intestinal Diseases/blood/chemically induced/*microbiology/pathology ; Mice, Inbred C57BL ; Mycophenolic Acid/*adverse effects ; Mice ; }, abstract = {BACKGROUND: Mycophenolic acid (MPA) is the most widely used immunosuppressive drug in transplantation and for autoimmune diseases. Unfortunately, more than 30% of patients experience a typical gastrointestinal adverse effect also referred to as mycophenolate-induced enteropathy. Due to its antibacterial, antifungal, and antiviral properties, MPA exposure is associated with intestinal dysbiosis characterized by a decrease in density and diversity of the microbiome regarding the main bacterial phyla (Firmicutes and Bacteroidetes). These bacterial phyla are known for their metabolic role in maintaining the homeostasis of the digestive tract, particularly through the production of short-chain fatty acids (SCFA) that could contribute to the pathophysiology of mycophenolate-induced enteropathy. Our study aimed at deciphering short-chain fatty acids (SCFA) profile alterations associated with gastrointestinal toxicity of MPA at the digestive and systemic levels in a mouse model.<br><br>METHODS: Ten-week old C57BL/6 (SOPF) mice were randomly assigned in 2 groups of 9 subjects: control, and mycophenolate mofetil (MMF, 900&#x2009;mg/kg/day). All mice were daily treated by oral gavage for 7&#x2009;days. Individual faecal pellets were collected at days 0, 4 and 8 as well as plasma at day 8 for SCFA profiling. Additionally, after the sacrifice on day 8, the caecum was weighted, and colon length was measured. The proximal colon was cut for histological analysis.<br><br>RESULTS: MMF treatment induced around 10% weight loss at the end of the protocol associated with a significant decrease in caecum weight and a slight reduction in colon length. Histological analysis showed significant architectural changes in colon epithelium. Moreover, we observed an overall decrease in SCFA concentrations in faecal samples, especially regarding acetate (at day 8, control 1040.6 &#xb1; 278.161&#x2009;&#x3bc;M versus MMF 384.7 &#xb1; 80.5&#x2009;&#x3bc;M, p < 0.01) and propionate (at day 8, control 185.94 &#xb1; 51.96&#x2009;&#x3bc;M versus MMF 44.07 &#xb1; 14.66&#x2009;&#x3bc;M, p < 0.001), and in plasma samples for butyrate (at day 8, control 0.91 &#xb1; 0.1&#x2009;&#x3bc;M versus MMF 0.46 &#xb1; 0.1&#x2009;&#x3bc;M, p < 0.01).<br><br>CONCLUSIONS: These results are consistent with functional impairment of the gut microbiome linked with digestive or systemic defects during MMF treatment.}, }
@article {pmid34709989, year = {2021}, author = {Ianiro, G and Bibbò, S and Porcari, S and Settanni, CR and Giambò, F and Curta, AR and Quaranta, G and Scaldaferri, F and Masucci, L and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: experience of a large-volume European FMT center.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1994834}, pmid = {34709989}, issn = {1949-0984}, mesh = {Adult ; Aged ; Clostridioides difficile/genetics/physiology ; Clostridium Infections/microbiology/*therapy ; Europe ; *Fecal Microbiota Transplantation ; Female ; Follow-Up Studies ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {Inflammatory bowel disease (IBD) is a risk factor for C. difficile infection (CDI), which, in turn, complicates the clinical course of IBD. Fecal microbiota transplantation (FMT) is safe and effective in patients with IBD and recurrent CDI (rCDI). In our study, patients with IBD and rCDI received FMT by colonoscopy and were followed-up for 8 weeks. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Eighteen patients with IBD were enrolled. Eight patients received sequential FMT either for pseudomembranous colitis or failure of single fecal infusion. At 8-week follow-up the C. difficile toxin was negative in 17 patients, and most (83%) experienced also improvement of IBD disease activity. Overall, we did not observe any serious adverse event.FMT appears to be highly effective and safe in patients with IBD and rCDI and is likely not only to eradicate CDI but also to improve disease activity of IBD.}, }
@article {pmid34709713, year = {2022}, author = {Elgarten, CW and Tanes, C and Lee, JJ and Danziger-Isakov, LA and Grimley, MS and Green, M and Michaels, MG and Barnum, JL and Ardura, MI and Auletta, JJ and Blumenstock, J and Seif, AE and Bittinger, KL and Fisher, BT}, title = {Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation.}, journal = {Pediatric blood &amp; cancer}, volume = {69}, number = {1}, pages = {e29384}, pmid = {34709713}, issn = {1545-5017}, support = {HHSN272201600014C/AI/NIAID NIH HHS/United States ; }, mesh = {Child ; Feces ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Humans ; Metabolome ; *Microbiota ; }, abstract = {BACKGROUND: The contribution of the gastrointestinal tract microbiome to outcomes after allogeneic hematopoietic cell transplantation (HCT) is increasingly recognized. Investigations of larger pediatric cohorts aimed at defining the microbiome state and associated metabolic patterns pretransplant are needed.<br><br>METHODS: We sought to describe the pretransplant stool microbiome in pediatric allogenic HCT patients at four centers. We performed shotgun metagenomic sequencing and untargeted metabolic profiling on pretransplant stool samples. Samples were compared with normal age-matched controls and by clinical characteristics. We then explored associations between stool microbiome measurements and metabolite concentrations.<br><br>RESULTS: We profiled stool samples from 88 pediatric allogeneic HCT patients, a median of 4&#xa0;days before transplant. Pretransplant stool samples differed from healthy controls based on indices of alpha diversity and in the proportional abundance of specific taxa and bacterial genes. Relative to stool from healthy patients, samples from HCT patients had decreased proportion of Bacteroides, Ruminococcaeae, and genes involved in butyrate production, but were enriched for gammaproteobacterial species. No systematic differences in stool microbiome or metabolomic profiles by age, transplant indication, or hospital were noted. Stool metabolites demonstrated strong correlations with microbiome composition.<br><br>DISCUSSION: Stool samples from pediatric allogeneic HCT patients demonstrate substantial dysbiosis early in the transplant course. As microbiome disruptions associate with adverse transplant outcomes, pediatric-specific analyses examining longitudinal microbiome and metabolome changes are imperative to identify causal associations and to inform rational design of interventions.}, }
@article {pmid34708542, year = {2022}, author = {Xie, J and Li, LF and Dai, TY and Qi, X and Wang, Y and Zheng, TZ and Gao, XY and Zhang, YJ and Ai, Y and Ma, L and Chang, SL and Luo, FX and Tian, Y and Sheng, J}, title = {Short-Chain Fatty Acids Produced by Ruminococcaceae Mediate α-Linolenic Acid Promote Intestinal Stem Cells Proliferation.}, journal = {Molecular nutrition &amp; food research}, volume = {66}, number = {1}, pages = {e2100408}, doi = {10.1002/mnfr.202100408}, pmid = {34708542}, issn = {1613-4133}, mesh = {Animals ; Cell Proliferation ; Fatty Acids, Volatile/metabolism ; Intestinal Mucosa/metabolism ; *Intestines ; Mice ; Stem Cells/physiology ; *alpha-Linolenic Acid/metabolism/pharmacology ; }, abstract = {SCOPE: The proliferation and differentiation of intestinal stem cells (ISCs) are the basis of intestinal renewal and regeneration, and gut microbiota plays an important role in it. Dietary nutrition has the effect of regulating the activity of ISCs; however, the regulation effect of α-linolenic acid (ALA) has seldom been reported.<br><br>METHODS AND RESULTS: After intervening mice with different doses of ALA for 30 days, it is found that ALA (0.5&#xa0;g kg[-1]) promotes small intestinal and villus growth by activating the Wnt/&#x3b2;-catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increases the abundance of the Ruminococcaceae and Prevotellaceae, and promotes the production of short-chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrate that ALA on the proliferation of ISCs are gut microbiota dependent, among them, the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate shows a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigates 5-fluorouracil-induced intestinal mucosal damage by promoting ISCs proliferation.<br><br>CONCLUSION: These results indicate that SCFAs produced by Ruminococcaceae mediate ALA promote ISCs proliferation by activating the Wnt/&#x3b2;-catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis.}, }
@article {pmid34706782, year = {2021}, author = {Lin, D and Hu, B and Li, P and Zhao, Y and Xu, Y and Wu, D}, title = {Roles of the intestinal microbiota and microbial metabolites in acute GVHD.}, journal = {Experimental hematology &amp; oncology}, volume = {10}, number = {1}, pages = {49}, pmid = {34706782}, issn = {2162-3619}, support = {BE2019655//social development project of jiangsu province/ ; BE2019798//jiangsu province key r&amp;d program/ ; 2019YFC0840604//national key research and development program/ ; 82020108003//national natural science foundation of china/ ; 82070187//national natural science foundation of china/ ; }, abstract = {Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most curative strategies for the treatment of many hematologic malignancies and diseases. However, acute graft-versus-host disease (GVHD) limits the success of allo-HSCT. The prevention and treatment of acute GVHD is the key issue for improving the efficacy of allo-HSCT and has become a research hotspot. The intestine is the primary organ targeted by acute GVHD, and the intestinal microbiota is critical for maintaining the homeostasis of the intestinal microenvironment and the immune response. Many studies have demonstrated the close association between the intestinal microbiota and the pathogenesis of acute GVHD. Furthermore, dysbiosis of the microbiota, which manifests as alterations in the diversity and composition of the intestinal microbiota, and alterations of microbial metabolites are pronounced in acute GVHD and associated with poor patient prognosis. The microbiota interacts with the host directly via microbial surface antigens or microbiota-derived metabolites to regulate intestinal homeostasis and the immune response. Therefore, intervention strategies targeting the intestinal microbiota, including antibiotics, prebiotics, probiotics, postbiotics and fecal microbiota transplantation (FMT), are potential new treatment options for acute GVHD. In this review, we discuss the alterations and roles of the intestinal microbiota and its metabolites in acute GVHD, as well as interventions targeting microbiota for the prevention and treatment of acute GVHD.}, }
@article {pmid34704776, year = {2021}, author = {Jan, N and Hays, RA and Oakland, DN and Kumar, P and Ramakrishnan, G and Behm, BW and Petri, WA and Marie, C}, title = {Fecal Microbiota Transplantation Increases Colonic IL-25 and Dampens Tissue Inflammation in Patients with Recurrent Clostridioides difficile.}, journal = {mSphere}, volume = {6}, number = {5}, pages = {e0066921}, pmid = {34704776}, issn = {2379-5042}, support = {R01 AI124214/AI/NIAID NIH HHS/United States ; R01 AI148518/AI/NIAID NIH HHS/United States ; R01 AI152477/AI/NIAID NIH HHS/United States ; }, mesh = {Aged ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/drug effects/pathogenicity ; Clostridium Infections/metabolism/microbiology/*therapy ; Colon/pathology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/metabolism/microbiology/therapy ; Interleukin-17/*metabolism ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility, and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of interleukin 25 (IL-25) and that FMT protected in part by restoring IL-25 signaling. Here, we conducted a prospective study in humans to test if FMT induced IL-25 expression in the colons of patients with recurrent CDI (rCDI). Colonic biopsy specimens and blood were collected at the time of FMT and 60 days later. Colon biopsy specimens were analyzed for IL-25 protein levels, total tissue transcriptome, and epithelium-associated microbiota before and after FMT, and peripheral immune cells were immunophenotyped. FMT increased alpha diversity of the colonic microbiota and levels of IL-25 in colonic tissue. In addition, FMT increased expression of homeostatic genes and repressed inflammatory genes. Finally, circulating Th17 cells were decreased post-FMT. The increase in levels of the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity. IMPORTANCE Fecal microbiota transplantation (FMT) is an effective treatment for C. difficile infection for most patients; however, introducing a complex mixture of microbes also has had unintended consequences for some patients. Attempts to create a standardized probiotic therapeutic that recapitulates the efficacy of FMT have been unsuccessful to date. We sought to understand what immune markers are changed in patients undergoing FMT to treat recurrent C. difficile infection and identified an immune signaling molecule, IL-25, that was restored by FMT. This finding indicates that adjunctive therapy with IL-25 could be useful in treating C. difficile infection.}, }
@article {pmid34704376, year = {2022}, author = {Zhu, L and Fu, J and Xiao, X and Wang, F and Jin, M and Fang, W and Wang, Y and Zong, X}, title = {Faecal microbiota transplantation-mediated jejunal microbiota changes halt high-fat diet-induced obesity in mice via retarding intestinal fat absorption.}, journal = {Microbial biotechnology}, volume = {15}, number = {1}, pages = {337-352}, pmid = {34704376}, issn = {1751-7915}, mesh = {Animals ; Diet, High-Fat/adverse effects ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Jejunum ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Obesity/therapy ; }, abstract = {Faecal Microbiota Transplantation (FMT) is considered as a promising technology to fight against obesity. Wild boar has leanermuscle and less fat in comparison to the domestic pig, which were thought to be related with microbiota. To investigate the function and mechanism of the wild boar microbiota on obesity, we first analysed the wild boar microbiota composition via 16S rDNA sequencing, which showed that Firmicutes and Proteobacteria were the dominant bacteria. Then, we established a high-fat diet (HFD)-induced obesity model, and transfer low and high concentrations of wild boar faecal suspension in mice for 9 weeks. The results showed that FMT prevented HFD-induced obesity and lipid metabolism disorders, and altered the jejunal microbiota composition especially increasing the abundance of the Lactobacillus and Romboutsia, which were negatively correlated with obesity-related indicators. Moreover, we found that the anti-obesity effect of wild boar faecal suspension was associated with jejunal N6-methyladenosine (m[6] A) levels. Overall, these results suggest that FMT has a mitigating effect on HFD-induced obesity, which may be due to the impressive effects of FMT on the microbial composition and structure of the jejunum. These changes further alter intestinal lipid metabolism and m[6] A levels to achieve resistance to obesity.}, }
@article {pmid34702350, year = {2021}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Nalluri, H and Kaiser, T and Holtan, SG and Khoruts, A and Weisdorf, DJ and Staley, C}, title = {Gut microbiota response to antibiotics is personalized and depends on baseline microbiota.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {211}, pmid = {34702350}, issn = {2049-2618}, support = {KL2TR002492//Foundation for the National Institutes of Health/ ; UL1TR002494//Foundation for the National Institutes of Health/ ; }, mesh = {*Anti-Bacterial Agents/adverse effects ; Dysbiosis/chemically induced ; Feces ; *Gastrointestinal Microbiome/drug effects ; Humans ; Leukemia/drug therapy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The magnitude of microbiota perturbations after exposure to antibiotics varies among individuals. It has been suggested that the composition of pre-treatment microbiota underpins personalized responses to antibiotics. However, this hypothesis has not been directly tested in humans. In this high-throughput amplicon study, we analyzed 16S ribosomal RNA gene sequences of 260 stool samples collected twice weekly from 39 patients with acute leukemia during their ~ 4 weeks of hospitalization for chemotherapy while they received multiple antibiotics.<br><br>RESULTS: Despite heavy and sustained antibiotic pressure, microbial communities in samples from the same patient remained more similar to one another than to those from other patients. Principal component mixed effect regression using microbiota and granular antibiotic exposure data showed that microbiota departures from baseline depend on the composition of the pre-treatment microbiota. Penalized generalized estimating equations identified 6 taxa within pre-treatment microbiota that predicted the extent of antibiotic-induced perturbations.<br><br>CONCLUSIONS: Our results indicate that specific species in pre-treatment microbiota determine personalized microbiota responses to antibiotics in humans. Thus, precision interventions targeting pre-treatment microbiota may prevent antibiotic-induced dysbiosis and its adverse clinical consequences. Video abstract.}, }
@article {pmid34699042, year = {2021}, author = {Mehmood, K and Moin, A and Hussain, T and Rizvi, SMD and Gowda, DV and Shakil, S and Kamal, MA}, title = {Can manipulation of gut microbiota really be transformed into an intervention strategy for cardiovascular disease management?.}, journal = {Folia microbiologica}, volume = {66}, number = {6}, pages = {897-916}, pmid = {34699042}, issn = {1874-9356}, mesh = {*Cardiovascular Diseases/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics ; *Synbiotics ; }, abstract = {Recent advancement in manipulation techniques of gut microbiota either ex vivo or in situ has broadened its plausible applicability for treating various diseases including cardiovascular disease. Several reports suggested that altering gut microbiota composition is an effective way to deal with issues associated with managing cardiovascular diseases. However, actual translation of gut microbiota manipulation-based techniques into cardiovascular-therapeutic approach is still questionable. This review summarized the evidence on challenges, opportunities, recent development, and future prospects of gut microbiota manipulation for targeting cardiovascular diseases. Initially, issues associated with current cardiovascular diseases treatment strategy, association of gut microbiota with cardiovascular disease, and its influence on cardiovascular drugs were discussed, followed by applicability of gut microbiota manipulation as a cardiovascular disease intervention strategy along with its challenges and future prospects. Despite the fact that the gut microbiota is rugged, interventions like probiotics, prebiotics, synbiotics, fecal microbiota transplantation, fecal virome transplantation, antibiotics, diet changes, and exercises could manipulate it. Advanced techniques like administration of engineered bacteriophages and bacteria could also be employed. Intensive exploration revealed that if sufficiently controlled approach and proper monitoring were applied, gut microbiota could provide a compelling answer for cardiovascular therapy.}, }
@article {pmid34696775, year = {2021}, author = {Li, N and Dai, Z and Wang, Z and Deng, Z and Zhang, J and Pu, J and Cao, W and Pan, T and Zhou, Y and Yang, Z and Li, J and Li, B and Ran, P}, title = {Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease.}, journal = {Respiratory research}, volume = {22}, number = {1}, pages = {274}, pmid = {34696775}, issn = {1465-993X}, mesh = {Aged ; Airway Remodeling ; Animals ; Bacteria/genetics/*growth &amp; development/metabolism ; Case-Control Studies ; China ; Cross-Sectional Studies ; Disease Models, Animal ; Disease Progression ; Dysbiosis ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Lung/pathology/*physiopathology ; Male ; Mice, Inbred C57BL ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/diagnosis/*microbiology/pathology/physiopathology ; Ribotyping ; Mice ; }, abstract = {BACKGROUND: Dysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood.<br><br>METHODS: We carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity. Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28&#xa0;days to induce pulmonary changes. Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes.<br><br>RESULTS: We observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids. After 28&#xa0;days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation. Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20&#xa0;weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed.<br><br>CONCLUSION: These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.}, }
@article {pmid34693389, year = {2021}, author = {Wortelboer, K and Herrema, H}, title = {Shedding light on dark matter - faecal microbiota transplantation in Europe.}, journal = {The Lancet regional health. Europe}, volume = {9}, number = {}, pages = {100187}, pmid = {34693389}, issn = {2666-7762}, }
@article {pmid34693388, year = {2021}, author = {Baunwall, SMD and Terveer, EM and Dahlerup, JF and Erikstrup, C and Arkkila, P and Vehreschild, MJ and Ianiro, G and Gasbarrini, A and Sokol, H and Kump, PK and Satokari, R and De Looze, D and Vermeire, S and Nakov, R and Brezina, J and Helms, M and Kjeldsen, J and Rode, AA and Kousgaard, SJ and Alric, L and Trang-Poisson, C and Scanzi, J and Link, A and Stallmach, A and Kupcinskas, J and Johnsen, PH and Garborg, K and Rodríguez, ES and Serrander, L and Brummer, RJ and Galpérine, KT and Goldenberg, SD and Mullish, BH and Williams, HR and Iqbal, TH and Ponsioen, C and Kuijper, EJ and Cammarota, G and Keller, JJ and Hvas, CL}, title = {The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey.}, journal = {The Lancet regional health. Europe}, volume = {9}, number = {}, pages = {100181}, pmid = {34693388}, issn = {2666-7762}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe.<br><br>METHODS: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT.<br><br>FINDINGS: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0&#x2022;3%) unaccounted for. Adjusted to population size, 0&#x2022;257 per 100,000 population received FMT for CDI and 0&#x2022;189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres.<br><br>INTERPRETATION: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need.<br><br>FUNDING: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).}, }
@article {pmid34691318, year = {2021}, author = {Alagiakrishnan, K and Halverson, T}, title = {Microbial Therapeutics in Neurocognitive and Psychiatric Disorders.}, journal = {Journal of clinical medicine research}, volume = {13}, number = {9}, pages = {439-459}, pmid = {34691318}, issn = {1918-3003}, abstract = {Microbial therapeutics, which include gut biotics and fecal transplantation, are interventions designed to improve the gut microbiome. Gut biotics can be considered as the administration of direct microbial populations. The delivery of this can be done through live microbial flora, certain food like fiber, microbial products (metabolites and elements) obtained through the fermentation of food products, or as genetically engineered substances, that may have therapeutic benefit on different health disorders. Dietary intervention and pharmacological supplements with gut biotics aim at correcting disruption of the gut microbiota by repopulating with beneficial microorganism leading to decrease in gut permeability, inflammation, and alteration in metabolic activities, through a variety of mechanisms of action. Our understanding of the pharmacokinetics of microbial therapeutics has improved with in vitro models, sampling techniques in the gut, and tools for the reliable identification of gut biotics. Evidence from human studies points out that prebiotics, probiotics and synbiotics have the potential for treating and preventing mental health disorders, whereas with paraprobiotics, proteobiotics and postbiotics, the research is limited at this point. Some animal studies point out that gut biotics can be used with conventional treatments for a synergistic effect on mental health disorders. If future research shows that there is a possibility of synergistic effect of psychotropic medications with gut biotics, then a gut biotic or nutritional prescription can be given along with psychotropics. Even though the overall safety of gut biotics seems to be good, caution is needed to watch for any known and unknown side effects as well as the need for risk benefit analysis with certain vulnerable populations. Future research is needed before wide spread use of natural and genetically engineered gut biotics. Regulatory framework for gut biotics needs to be optimized. Holistic understanding of gut dysbiosis, along with life style factors, by health care providers is necessary for the better management of these conditions. In conclusion, microbial therapeutics are a new psychotherapeutic approach which offer some hope in certain conditions like dementia and depression. Future of microbial therapeutics will be driven by well-done randomized controlled trials and longitudinal research, as well as by replication studies in human subjects.}, }
@article {pmid34691046, year = {2021}, author = {Wen, S and He, L and Zhong, Z and Zhao, R and Weng, S and Mi, H and Liu, F}, title = {Stigmasterol Restores the Balance of Treg/Th17 Cells by Activating the Butyrate-PPARγ Axis in Colitis.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {741934}, pmid = {34691046}, issn = {1664-3224}, mesh = {Animals ; Anti-Inflammatory Agents/pharmacology ; Butyrates/metabolism ; Cell Differentiation/immunology ; Colitis/*immunology ; Gastrointestinal Microbiome/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; PPAR gamma/drug effects/metabolism ; Stigmasterol/*pharmacology ; T-Lymphocytes, Regulatory/*drug effects/immunology/metabolism ; Th17 Cells/*drug effects/immunology/metabolism ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with gut microbiota disequilibrium and regulatory T (Treg)/T helper 17 (Th17) immune imbalance. Stigmasterol, a plant-derived sterol, has shown anti-inflammatory effects. Our study aimed to identify the effects of stigmasterol on experimental colitis and the related mechanisms. Stigmasterol treatment restored the Treg/Th17 balance and altered the gut microbiota in a dextran sodium sulfate (DSS)-induced colitis model. Transplantation of the faecal microbiota of stigmasterol-treated mice significantly alleviated inflammation. Additionally, stigmasterol treatment enhanced the production of gut microbiota-derived short-chain fatty acids (SCFAs), particularly butyrate. Next, human naïve CD4+ T cells sorted from IBD patients were cultured under Treg- or Th17-polarizing conditions; butyrate supplementation increased the differentiation of Tregs and decreased Th17 cell differentiation. Mechanistically, butyrate activated peroxisome proliferator-activated receptor gamma (PPARγ) and reprogrammed energy metabolism, thereby promoting Treg differentiation and inhibiting Th17 differentiation. Our results demonstrate that butyrate-mediated PPARγ activation restores the balance of Treg/Th17 cells, and this may be a possible mechanism, by which stigmasterol attenuates IBD.}, }
@article {pmid34690981, year = {2021}, author = {Fu, X and Chen, T and Cai, J and Liu, B and Zeng, Y and Zhang, X}, title = {The Microbiome-Gut-Brain Axis, a Potential Therapeutic Target for Substance-Related Disorders.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {738401}, pmid = {34690981}, issn = {1664-302X}, abstract = {Substance addiction is a complex worldwide public health problem. It endangers both personal life and social stability, causing great loss on economy. Substance-related disorder is considered to be a complicated chronic brain disorder. It resulted from interactions among pharmacological properties of addictive substances, individual susceptibility, and social-environmental factors. Unfortunately, there is still no ideal treatment for this disorder. Recent lines of evidence suggest that gut microbiome may play an important role in the pathogenesis of neuropsychiatric disorders, including substance-related disorders. This review summarizes the research on the relationship between gut microbiome and substance-related disorders, including different types of substance, different individual susceptibility, and the occurrence and development of substance-induced mental disorders. We also discuss the potentiation of gut microbiome in the treatment of substance-related disorders, especially in the treatment of substance-induced mental disorders and manipulation on individuals' responsiveness to addictive substances.}, }
@article {pmid34690948, year = {2021}, author = {Zhang, X and Li, N and Chen, Q and Qin, H}, title = {Fecal Microbiota Transplantation Modulates the Gut Flora Favoring Patients With Functional Constipation.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {700718}, pmid = {34690948}, issn = {1664-302X}, abstract = {Intestinal dysmotility is common in many diseases and is correlated with gut microbiota dysbiosis and systemic inflammation. Functional constipation (FC) is the most typical manifestation of intestinal hypomotility and reduces patients' quality of life. Some studies have reported that fecal micriobiota transplantation (FMT) may be an effective and safe therapy for FC as it corrects intestinal dysbiosis. This study was conducted to evaluate how FMT remodels the gut microbiome and to determine a possible correlation between certain microbes and clinical symptoms in constipated individuals. Data were retrospectively collected on 18 patients who underwent FMT between January 1, 2019 and June 30, 2020. The fecal bacterial genome was detected by sequencing the V3-V4 hypervariable regions of the 16S rDNA gene. Fecal short chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry, and serum inflammatory factor concentrations were detected via enzyme-linked immunosorbent assay. Comparing the changes in fecal microbiome compositions before and after FMT revealed a significant augmentation in the alpha diversity and increased abundances of some flora such as Clostridiales, Fusicatenibacter, and Paraprevotella. This was consistent with the patients experiencing relief from their clinical symptoms. Abundances of other flora, including Lachnoanaerobaculum, were decreased, which might correlate with the severity of patients' constipation. Although no differences were found in SCFA production, the butyric acid concentration was correlated with both bacterial alterations and clinical symptoms. Serum IL-8 levels were significantly lower after FMT than at baseline, but IL-4, IL-6, IL-10, and IL-12p70 levels were not noticeably changed. This study showed how FMT regulates the intestinal microenvironment and affects systemic inflammation in constipated patients, providing direction for further research on the mechanisms of FMT. It also revealed potential microbial targets for precise intervention, which may bring new breakthroughs in treating constipation.}, }
@article {pmid34684567, year = {2021}, author = {Rousta, E and Oka, A and Liu, B and Herzog, J and Bhatt, AP and Wang, J and Habibi Najafi, MB and Sartor, RB}, title = {The Emulsifier Carboxymethylcellulose Induces More Aggressive Colitis in Humanized Mice with Inflammatory Bowel Disease Microbiota Than Polysorbate-80.}, journal = {Nutrients}, volume = {13}, number = {10}, pages = {}, pmid = {34684567}, issn = {2072-6643}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; P01DK094779, P40OD010995, P30DK034987, K01DK119582//the US Public Health Service National Institutes of Health (NIH)/ ; #2434 and 708151//the Crohn's &amp; Colitis Foundation/ ; }, mesh = {Animals ; Biomarkers/metabolism ; Body Weight/drug effects ; Carboxymethylcellulose Sodium/*adverse effects ; Colitis/*chemically induced/*microbiology/pathology ; Colon/metabolism/pathology ; Emulsifying Agents/*adverse effects ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Gene Expression Regulation/drug effects ; Humans ; Inflammation/pathology ; Inflammatory Bowel Diseases/*microbiology ; Male ; Metabolic Networks and Pathways/drug effects ; Mice, Inbred C57BL ; Polysorbates/*adverse effects ; RNA, Messenger/genetics/metabolism ; Mice ; }, abstract = {Commonly used synthetic dietary emulsifiers, including carboxymethylcellulose (CMC) and polysorbate-80 (P80), promote intestinal inflammation. We compared abilities of CMC vs. P80 to potentiate colitis and impact human microbiota in an inflammatory environment using a novel colitis model of ex-germ-free (GF) IL10[-/-] mice colonized by pooled fecal transplant from three patients with active inflammatory bowel diseases. After three days, mice received 1% CMC or P80 in drinking water or water alone for four weeks. Inflammation was quantified by serial fecal lipocalin 2 (Lcn-2) and after four weeks by blinded colonic histologic scores and colonic inflammatory cytokine gene expression. Microbiota profiles in cecal contents were determined by shotgun metagenomic sequencing. CMC treatment significantly increased fecal Lcn-2 levels compared to P80 and water treatment by one week and throughout the experiment. Likewise, CMC treatment increased histologic inflammatory scores and colonic inflammatory cytokine gene expression compared with P80 and water controls. The two emulsifiers differentially affected specific intestinal microbiota. CMC did not impact bacterial composition but significantly decreased Caudoviricetes (bacteriophages), while P80 exposure non-significantly increased the abundance of both Actinobacteria and Proteobacteria. Commonly used dietary emulsifiers have different abilities to induce colitis in humanized mice. CMC promotes more aggressive inflammation without changing bacterial composition.}, }
@article {pmid34684330, year = {2021}, author = {Tanaka, Y and Shimizu, S and Shirotani, M and Yorozu, K and Kitamura, K and Oehorumu, M and Kawai, Y and Fukuzawa, Y}, title = {Nutrition and Cancer Risk from the Viewpoint of the Intestinal Microbiome.}, journal = {Nutrients}, volume = {13}, number = {10}, pages = {}, pmid = {34684330}, issn = {2072-6643}, mesh = {Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Neoplasms/*epidemiology/*microbiology ; *Nutritional Status ; Risk Factors ; }, abstract = {There are various important factors in reducing the risk of cancer development and progression; these factors may correct an unbalanced intake of nutrients to maintain the living body's homeostasis, detoxify toxic materials, acting as an external factor, and maintain and strengthen the body's immune function. In a normal cell environment, nutrients, such as carbohydrates, lipids, proteins, vitamins, and minerals, are properly digested and absorbed into the body, and, as a result, an environment in which cancer can develop and progress is prevented. It is necessary to prevent toxic materials from entering the body and to detoxify poisons in the body. If these processes occur correctly, cells work normally, and genes cannot be damaged. The most important factor in the fight against cancer and prevention of the development and progression of cancer is the immune system. This requires a nutritional state in which the immune system works well, allowing the intestinal microbiome to carry out all of its roles. In order to grow intestinal microbiota, the consumption of prebiotics, such as organic vegetables, fruits, and dietary fiber, and probiotics of effective intestinal microbiota, such as fermented foods and supplements, is required. Symbiosis, in which these organisms work together, is an effective means of reducing the risk of cancer. In addition, fecal microbiota transplantation (FMT) using ultrafine bubble water, produced specially by the Association for Clinical Research of Fecal Microbiota Transplantation Japan, is also useful for improving the nutritional condition and reducing the risk of cancer.}, }
@article {pmid34680424, year = {2021}, author = {Tourelle, KM and Boutin, S and Weigand, MA and Schmitt, FCF}, title = {The Association of Gut Microbiota and Complications in Gastrointestinal-Cancer Therapies.}, journal = {Biomedicines}, volume = {9}, number = {10}, pages = {}, pmid = {34680424}, issn = {2227-9059}, abstract = {The therapy of gastrointestinal carcinomas includes surgery, chemo- or immunotherapy, and radiation with diverse complications such as surgical-site infection and enteritis. In recent years, the microbiome's influence on different diseases and complications has been studied in more detail using methods such as next-generation sequencing. Due to the relatively simple collectivisation, the gut microbiome is the best-studied so far. While certain bacteria are sometimes associated with one particular complication, it is often just the loss of alpha diversity linked together. Among others, a strong influence of Fusobacterium nucleatum on the effectiveness of chemotherapies is demonstrated. External factors such as diet or specific medications can also predispose to dysbiosis and lead to complications. In addition, there are attempts to treat developed dysbiosis, such as faecal microbiota transplant or probiotics. In the future, the underlying microbiome should be investigated in more detail for a better understanding of the precipitating factors of a complication with specific therapeutic options.}, }
@article {pmid34680092, year = {2021}, author = {Cibulková, I and Řehořová, V and Hajer, J and Duška, F}, title = {Fecal Microbial Transplantation in Critically Ill Patients-Structured Review and Perspectives.}, journal = {Biomolecules}, volume = {11}, number = {10}, pages = {}, pmid = {34680092}, issn = {2218-273X}, mesh = {Critical Illness/*epidemiology ; Diarrhea/epidemiology/microbiology/*therapy ; Dysbiosis/epidemiology/microbiology/*therapy ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome/genetics ; Humans ; Inflammatory Bowel Diseases/epidemiology/microbiology/*therapy ; }, abstract = {The human gut microbiota consists of bacteria, archaea, fungi, and viruses. It is a dynamic ecosystem shaped by several factors that play an essential role in both healthy and diseased states of humans. A disturbance of the gut microbiota, also termed "dysbiosis", is associated with increased host susceptibility to a range of diseases. Because of splanchnic ischemia, exposure to antibiotics, and/or the underlying disease, critically ill patients loose 90% of the commensal organisms in their gut within hours after the insult. This is followed by a rapid overgrowth of potentially pathogenic and pro-inflammatory bacteria that alter metabolic, immune, and even neurocognitive functions and that turn the gut into the driver of systemic inflammation and multiorgan failure. Indeed, restoring healthy microbiota by means of fecal microbiota transplantation (FMT) in the critically ill is an attractive and plausible concept in intensive care. Nonetheless, available data from controlled studies are limited to probiotics and FMT for severe C. difficile infection or severe inflammatory bowel disease. Case series and observational trials have generated hypotheses that FMT might be feasible and safe in immunocompromised patients, refractory sepsis, or severe antibiotic-associated diarrhea in ICU. There is a burning need to test these hypotheses in randomized controlled trials powered for the determination of patient-centered outcomes.}, }
@article {pmid34679798, year = {2021}, author = {Laustsen, L and Edwards, JE and Hermes, GDA and Lúthersson, N and van Doorn, DA and Okrathok, S and Kujawa, TJ and Smidt, H}, title = {Free Faecal Water: Analysis of Horse Faecal Microbiota and the Impact of Faecal Microbial Transplantation on Symptom Severity.}, journal = {Animals : an open access journal from MDPI}, volume = {11}, number = {10}, pages = {}, pmid = {34679798}, issn = {2076-2615}, abstract = {Free faecal water (FFW) in equines results in pollution of the hindquarters and tail and can also involve clinical signs. Though the cause of FFW is unknown, it was hypothesized that it may involve the gut microbiota. This hypothesis was addressed as follows. First, the faecal prokaryotic community composition of horses suffering from FFW relative to healthy controls (n = 10) was compared. Second, FFW horses were treated with a standardised faecal microbiota transplantation (FMT) protocol (n = 10), followed by assessment of FFW symptom severity and faecal prokaryotic community composition over a follow-up period of 168 days. No significant differences were found in the faecal microbiota composition of FFW horses compared to healthy controls (p > 0.05). Relative to before FMT, FFW symptom severity decreased in affected horses 14 days after FMT (p = 0.02) and remained decreased for the remainder of the study (p < 0.02). However, individual animal responses to FMT varied. FMT had no effect on FFW horse faecal prokaryotic community composition in terms of alpha or beta diversity. Alpha diversity of the donor inocula used in the FMT was always lower than that of the faecal microbiota of the FFW treated horses (p < 0.001). In conclusion, whilst findings indicate FFW horses do not have an altered hindgut microbiota, some horses that received FMT had a temporary alleviation of FFW symptom severity without causing changes in the faecal microbiota. Future studies using controls are now needed to confirm the effectiveness of FMT to treat FFW.}, }
@article {pmid34678515, year = {2021}, author = {van Prehn, J and Reigadas, E and Vogelzang, EH and Bouza, E and Hristea, A and Guery, B and Krutova, M and Norén, T and Allerberger, F and Coia, JE and Goorhuis, A and van Rossen, TM and Ooijevaar, RE and Burns, K and Scharvik Olesen, BR and Tschudin-Sutter, S and Wilcox, MH and Vehreschild, MJGT and Fitzpatrick, F and Kuijper, EJ and , }, title = {European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {27 Suppl 2}, number = {}, pages = {S1-S21}, doi = {10.1016/j.cmi.2021.09.038}, pmid = {34678515}, issn = {1469-0691}, mesh = {Adult ; *Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal ; Broadly Neutralizing Antibodies ; Clostridioides difficile ; *Clostridium Infections/diagnosis/drug therapy ; Fidaxomicin ; Humans ; *Practice Guidelines as Topic ; Recurrence ; Societies, Medical ; Vancomycin ; }, abstract = {SCOPE: In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as faecal microbiota transplantation (FMT) and toxin-binding monoclonal antibodies, prompted the ESCMID study group on C. difficile (ESGCD) to update the 2014 treatment guidance document for CDI in adults.<br><br>METHODS AND QUESTIONS: Key questions on CDI treatment were formulated by the guideline committee and included: What is the best treatment for initial, severe, severe-complicated, refractory, recurrent and multiple recurrent CDI? What is the best treatment when no oral therapy is possible? Can prognostic factors identify patients at risk for severe and recurrent CDI and is there a place for CDI prophylaxis? Outcome measures for treatment strategy were: clinical cure, recurrence and sustained cure. For studies on surgical interventions and severe-complicated CDI the outcome was mortality. Appraisal of available literature and drafting of recommendations was performed by the guideline drafting group. The total body of evidence for the recommendations on CDI treatment consists of the literature described in the previous guidelines, supplemented with a systematic literature search on randomized clinical trials and observational studies from 2012 and onwards. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The guideline committee was invited to comment on the recommendations. The guideline draft was sent to external experts and a patients' representative for review. Full ESCMID endorsement was obtained after a public consultation procedure.<br><br>RECOMMENDATIONS: Important changes compared with previous guideline include but are not limited to: metronidazole is no longer recommended for treatment of CDI when fidaxomicin or vancomycin are available, fidaxomicin is the preferred agent for treatment of initial CDI and the first recurrence of CDI when available and feasible, FMT or bezlotoxumab in addition to standard of care antibiotics (SoC) are preferred for treatment of a second or further recurrence of CDI, bezlotoxumab in addition to SoC is recommended for the first recurrence of CDI when fidaxomicin was used to manage the initial CDI episode, and bezlotoxumab is considered as an ancillary treatment to vancomycin for a CDI episode with high risk of recurrence when fidaxomicin is not available. Contrary to the previous guideline, in the current guideline emphasis is placed on risk for recurrence as a factor that determines treatment strategy for the individual patient, rather than the disease severity.}, }
@article {pmid34676841, year = {2021}, author = {Ma, C and He, J and Lai, L and Chen, Y and Xue, W and Chen, J and Dai, W and Tang, D and Yan, Q and Dai, Y}, title = {Intestinal microbiome and metabolome analyses reveal metabolic disorders in the early stage of renal transplantation.}, journal = {Molecular omics}, volume = {17}, number = {6}, pages = {985-996}, doi = {10.1039/d1mo00279a}, pmid = {34676841}, issn = {2515-4184}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Kidney Transplantation ; *Metabolic Diseases ; Metabolome ; RNA, Ribosomal, 16S ; }, abstract = {Renal transplantation is the most effective treatment for end-stage renal disease, but the long-term prognosis of organs after transplantation is not ideal. In recent years, the importance of gut microbes and metabolites in the study of disease mechanisms has gradually received attention. However, the coordination between gut microbes and the metabolism of renal transplant patients needs further study. We integrated 16s sequencing and metabolomics data to describe the changes in the serum and fecal metabolites of renal transplant patients. Our data revealed that the gut microbial diversity decreased and the relative abundance of many bacteria, such as Enterococcus and Streptococcus, significantly changed after transplantation. In addition, a large number of amino acids and peptides in serum and feces significantly changed, suggesting an abnormal amino acid metabolism after transplantation. Spearman's correlation analysis revealed the changes in the co-metabolism pattern between gut microbes and the host metabolism after transplantation. Furthermore, Enterococcus was found to be correlated with renal functions and metabolites reflecting renal damage. This study provides potential gut microbes and metabolites impacting renal health, which helps in understanding the renal damage in patients with kidney transplantation.}, }
@article {pmid34675599, year = {2021}, author = {Zheng, Y and Ding, Y and Xu, M and Chen, H and Zhang, H and Liu, Y and Shen, W and Li, J}, title = {Gut Microbiota Contributes to Host Defense Against Klebsiella pneumoniae-Induced Liver Abscess.}, journal = {Journal of inflammation research}, volume = {14}, number = {}, pages = {5215-5225}, pmid = {34675599}, issn = {1178-7031}, abstract = {PURPOSE: Klebsiella pneumoniae-induced liver abscess (KLA) is a type of pyogenic liver abscess (PLA), which is a distinct invasive syndrome that has been increasingly reported worldwide over the past two decades. The intestinal microbiota is increasingly recognized as an important modulator that can promote and maintain host immune homeostasis. However, its precise role in liver abscess is unknown. We aimed to investigate the function of the gut microbiota in the host defense against K. pneumoniae infection.<br><br>METHODS: We constructed C57BL/6J mice with KLA and analyzed the diversity and richness of the intestinal microflora by 16S rRNA sequencing. Next, to create a microbiota-depleted (MD) mouse model, we administered multiple broad-spectrum antibiotics and validated the model using 16S rRNA sequencing. At 48 h after K. pneumoniae infection, we assessed the general health condition, liver injury, bacterial loads, and inflammatory factor levels in MD+KLA mice. Additionally, fecal microbiota transplantation (FMT) was conducted in another group of MD+KLA mice prior to K. pneumoniae infection, and we assessed whether the transplantation changed the outcomes.<br><br>RESULTS: The diversity of the intestinal flora was significantly changed in KLA mice compared to control mice, with a decrease in beneficial bacteria and an increase in harmful bacteria. The MD+KLA mice exhibited impaired antimicrobial capacity, reduced survival, increased inflammation and liver damage at 48 h after K. pneumoniae infection compared to the KLA mice. However, FMT normalized the inflammatory cytokine levels, reduced liver damage, and increased survival.<br><br>CONCLUSION: This study identified the gut microbiota as a protective factor against K. pneumoniae infection. The role of FMT in KLA should be investigated in future clinical studies.}, }
@article {pmid34673840, year = {2021}, author = {Gregory, AL and Pensinger, DA and Hryckowian, AJ}, title = {A short chain fatty acid-centric view of Clostridioides difficile pathogenesis.}, journal = {PLoS pathogens}, volume = {17}, number = {10}, pages = {e1009959}, pmid = {34673840}, issn = {1553-7374}, mesh = {Animals ; Clostridioides difficile/*metabolism ; Clostridium Infections/*metabolism ; Fatty Acids, Volatile/*metabolism ; Gastrointestinal Microbiome/physiology ; Host-Pathogen Interactions/*physiology ; Humans ; }, abstract = {Clostridioides difficile is an opportunistic diarrheal pathogen responsible for significant morbidity and mortality worldwide. A disrupted (dysbiotic) gut microbiome, commonly engendered by antibiotic treatment, is the primary risk factor for C. difficile infection, highlighting that C. difficile-microbiome interactions are critical for determining the fitness of this pathogen. Here, we review short chain fatty acids (SCFAs): a major class of metabolites present in the gut, their production by the gut microbiome, and their impacts on the biology of the host and of C. difficile. We use these observations to illustrate a conceptual model whereby C. difficile senses and responds to SCFAs as a marker of a healthy gut and tunes its virulence accordingly in order to maintain dysbiosis. Future work to learn the molecular mechanisms and genetic circuitry underlying the relationships between C. difficile and SCFAs will help to identify precision approaches, distinct from antibiotics and fecal transplant, for mitigating disease caused by C. difficile and will inform similar investigations into other gastrointestinal pathogens.}, }
@article {pmid34670821, year = {2021}, author = {Zheng, Z and Aweya, JJ and Bao, S and Yao, D and Li, S and Tran, NT and Ma, H and Zhang, Y}, title = {The Microbial Composition of Penaeid Shrimps' Hepatopancreas Is Modulated by Hemocyanin.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {207}, number = {11}, pages = {2733-2743}, doi = {10.4049/jimmunol.2100746}, pmid = {34670821}, issn = {1550-6606}, mesh = {Animals ; Energy Metabolism ; Hemocyanins/immunology/*metabolism ; Hepatopancreas/immunology/*metabolism ; Penaeidae/immunology/metabolism/*microbiology ; }, abstract = {Aquatic organisms have to produce proteins or factors that help maintain a stable relationship with microbiota and prevent colonization by pathogenic microorganisms. In crustaceans and other aquatic invertebrates, relatively few of these host factors have been characterized. In this study, we show that the respiratory glycoprotein hemocyanin is a crucial host factor that modulates microbial composition and diversity in the hepatopancreas of penaeid shrimp. Diseased penaeid shrimp (Penaeus vannamei), had an empty gastrointestinal tract with atrophied hepatopancreas, expressed low hemocyanin, and high total bacterial abundance, with Vibrio as the dominant bacteria. Similarly, shrimp depleted of hemocyanin had mitochondrial depolarization, increased reactive oxygen species (ROS) levels, and dysregulation of several energy metabolism-related genes. Hemocyanin silencing together with ROS scavenger (N-acetylcysteine) treatment improved microbial diversity and decreased Vibrio dominance in the hepatopancreas. However, fecal microbiota transplantation after hemocyanin knockdown could not restore the microbial composition in the hepatopancreas. Collectively, our data provide, to our knowledge, new insight into the pivotal role of hemocyanin in modulating microbial composition in penaeid shrimp hepatopancreas via its effect on mitochondrial integrity, energy metabolism, and ROS production.}, }
@article {pmid34668771, year = {2022}, author = {Larsen, BB and Gryseels, S and Otto, HW and Worobey, M}, title = {Evolution and Diversity of Bat and Rodent Paramyxoviruses from North America.}, journal = {Journal of virology}, volume = {96}, number = {3}, pages = {e0109821}, pmid = {34668771}, issn = {1098-5514}, mesh = {Amino Acid Sequence ; Animal Diseases/diagnosis/*epidemiology/*virology ; Animals ; Arizona/epidemiology ; Biodiversity ; Biological Evolution ; Chiroptera/*virology ; Genome, Viral ; Genomics/methods ; Geography, Medical ; High-Throughput Nucleotide Sequencing ; Host Specificity ; Humans ; Models, Molecular ; Molecular Diagnostic Techniques/methods ; North America/epidemiology ; Paramyxoviridae/*classification/*genetics ; Paramyxoviridae Infections/*veterinary ; Phylogeny ; Protein Binding ; RNA, Viral ; Receptors, Virus/chemistry/metabolism ; Respirovirus/classification/genetics ; Respirovirus Infections/veterinary ; Rodentia/virology ; }, abstract = {Paramyxoviruses are a diverse group of negative-sense, single-stranded RNA viruses of which several species cause significant mortality and morbidity. In recent years the collection of paramyxovirus sequences detected in wild mammals has substantially grown; however, little is known about paramyxovirus diversity in North American mammals. To better understand natural paramyxovirus diversity, host range, and host specificity, we sought to comprehensively characterize paramyxoviruses across a range of diverse cooccurring wild small mammals in southern Arizona. We used highly degenerate primers to screen fecal and urine samples and obtained a total of 55 paramyxovirus sequences from 12 rodent species and 6 bat species. We also performed Illumina transcriptome sequencing (RNA-seq) and de novo assembly on 14 of the positive samples to recover a total of 5 near-full-length viral genomes. We show there are at least two clades of rodent-borne paramyxoviruses in Arizona, while bat-associated paramyxoviruses formed a putative single clade. Using structural homology modeling of the viral attachment protein, we infer that three of the five novel viruses likely bind sialic acid in a manner similar to other respiroviruses, while the other two viruses from heteromyid rodents likely bind a novel host receptor. We find no evidence for cross-species transmission, even among closely related sympatric host species. Taken together, these data suggest paramyxoviruses are a common viral infection in some bat and rodent species present in North America and illuminate the evolution of these viruses. IMPORTANCE There are a number of viral lineages that are potential zoonotic threats to humans. One of these, paramyxoviruses have jumped into humans multiple times from wild and domestic animals. We conducted one of the largest viral surveys of wild mammals in the United States to better understand paramyxovirus diversity and evolution.}, }
@article {pmid34668228, year = {2022}, author = {Sung, JJY and Wong, SH}, title = {What is unknown in using microbiota as a therapeutic?.}, journal = {Journal of gastroenterology and hepatology}, volume = {37}, number = {1}, pages = {39-44}, doi = {10.1111/jgh.15716}, pmid = {34668228}, issn = {1440-1746}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Fecal microbiota transplantation (FMT) has been used extensively in the treatment of various gastrointestinal and extraintestinal conditions, despite that there are still a lot of missing gaps in our knowledge in the gut microbiota and its behavior. This article describes the unknowns in microbiota biology (undetected microbes, uncertain colonization, unclear mechanisms of action, uncertain indications, unsure long-term efficacy, or side effects). We discuss how these unknowns may affect the therapeutic uses of FMT, and the potentials and caveats of other related microbiota-based therapies. When used as an experimental therapy or last resort in difficult conditions, caution should be taken against inadvertent complications. Clear documentations of post-treatment events should be made mandatory, classified, and graded as in clinical trials. Further robust scientific experiments and properly designed clinical studies are needed.}, }
@article {pmid34666171, year = {2021}, author = {Wu, W and Zhou, D and Xuan, R and Zhou, J and Liu, J and Chen, J and Han, H and Niu, T and Li, X and Chen, H and Wang, F}, title = {λ-carrageenan exacerbates Citrobacter rodentium-induced infectious colitis in mice by targeting gut microbiota and intestinal barrier integrity.}, journal = {Pharmacological research}, volume = {174}, number = {}, pages = {105940}, doi = {10.1016/j.phrs.2021.105940}, pmid = {34666171}, issn = {1096-1186}, mesh = {Animals ; Carrageenan/*adverse effects ; *Citrobacter rodentium ; *Colitis/etiology/metabolism/microbiology ; Cytokines/analysis ; *Enterobacteriaceae Infections/complications/metabolism/microbiology ; Fatty Acids, Volatile/metabolism ; Feces/chemistry/microbiology ; Gastrointestinal Microbiome/*drug effects/genetics ; Intestinal Mucosa/*drug effects/metabolism ; Lipopolysaccharides/analysis ; Male ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; Mice ; }, abstract = {For nearly half a century, the scientific community has been unable to agree upon the safety profile of carrageenan (CGN), a ubiquitous food additive. Little is known about the mechanisms by which consumption of CGN aggravates the etiopathogenesis of murine colitis. However, analyses of gut microbiota and intestinal barrier integrity have provided a breakthrough in explaining the synergistic effect of CGN upon colitis. In Citrobacter rodentium-induced infectious murine colitis, inflammation and the clinical severity of gut tissue were aggravated in the presence of λ-CGN. Using fecal transplantation and germ-free mice experiments, we evaluated the role of intestinal microbiota on the pro-inflammatory effect of λ-CGN. Mice with high dietary λ-CGN consumption showed altered colonic microbiota composition that resulted in degradation of the colonic mucus layer, a raised fecal LPS level, and a decrease in the presence of bacterially derived short-chain fatty acids (SCFAs). Mucus layer defects and altered fecal LPS and SCFA levels could be reproduced in germ-free mice by fecal transplantation from CGN-H-fed mice, but not from germ-free CGN-H-fed mice. Our results confirm that λ-CGN may create an environment that favors inflammation by altering gut microbiota composition and gut bacterial metabolism. The present study provides evidence that the "gut microbiota-barrier axis" could be an alternative target for ameliorating the colitis promoting effect of λ-CGN.}, }
@article {pmid34665009, year = {2021}, author = {Van Espen, L and Bak, EG and Beller, L and Close, L and Deboutte, W and Juel, HB and Nielsen, T and Sinar, D and De Coninck, L and Frithioff-Bøjsøe, C and Fonvig, CE and Jacobsen, S and Kjærgaard, M and Thiele, M and Fullam, A and Kuhn, M and Holm, JC and Bork, P and Krag, A and Hansen, T and Arumugam, M and Matthijnssens, J}, title = {A Previously Undescribed Highly Prevalent Phage Identified in a Danish Enteric Virome Catalog.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0038221}, pmid = {34665009}, issn = {2379-5077}, support = {NNF18CC0034900//Novo Nordisk Foundation/ ; NNF15OC0016692//Novo Nordisk Foundation/ ; NNF15OC0016544//Novo Nordisk Foundation/ ; 0603-00484B//Innovation Fund Denmark/ ; //Region Zealand Health Scientific Research Foundation/ ; 668031//European Union's Horizon2020/ ; 1S61618N//Fonds Wetenschappelijk Onderzoek (FWO)/ ; 1S25720N//Fonds Wetenschappelijk Onderzoek (FWO)/ ; }, abstract = {Gut viruses are important, yet often neglected, players in the complex human gut microbial ecosystem. Recently, the number of human gut virome studies has been increasing; however, we are still only scratching the surface of the immense viral diversity. In this study, 254 virus-enriched fecal metagenomes from 204 Danish subjects were used to generate the Danish Enteric Virome Catalog (DEVoC) containing 12,986 nonredundant viral scaffolds, of which the majority was previously undescribed, encoding 190,029 viral genes. The DEVoC was used to compare 91 healthy DEVoC gut viromes from children, adolescents, and adults that were used to create the DEVoC. Gut viromes of healthy Danish subjects were dominated by phages. While most phage genomes (PGs) only occurred in a single subject, indicating large virome individuality, 39 PGs were present in more than 10 healthy subjects. Among these 39 PGs, the prevalences of three PGs were associated with age. To further study the prevalence of these 39 prevalent PGs, 1,880 gut virome data sets of 27 studies from across the world were screened, revealing several age-, geography-, and disease-related prevalence patterns. Two PGs also showed a remarkably high prevalence worldwide-a crAss-like phage (20.6% prevalence), belonging to the tentative AlphacrAssvirinae subfamily, and a previously undescribed circular temperate phage infecting Bacteroides dorei (14.4% prevalence), called LoVEphage because it encodes lots of viral elements. Due to the LoVEphage's high prevalence and novelty, public data sets in which the LoVEphage was detected were de novo assembled, resulting in an additional 18 circular LoVEphage-like genomes (67.9 to 72.4 kb). IMPORTANCE Through generation of the DEVoC, we added numerous previously uncharacterized viral genomes and genes to the ever-increasing worldwide pool of human gut viromes. The DEVoC, the largest human gut virome catalog generated from consistently processed fecal samples, facilitated the analysis of the 91 healthy Danish gut viromes. Characterizing the biggest cohort of healthy gut viromes from children, adolescents, and adults to date confirmed the previously established high interindividual variation in human gut viromes and demonstrated that the effect of age on the gut virome composition was limited to the prevalence of specific phage (groups). The identification of a previously undescribed prevalent phage illustrates the usefulness of developing virome catalogs, and we foresee that the DEVoC will benefit future analysis of the roles of gut viruses in human health and disease.}, }
@article {pmid34664371, year = {2021}, author = {Fehily, SR and Basnayake, C and Wright, EK and Kamm, MA}, title = {The gut microbiota and gut disease.}, journal = {Internal medicine journal}, volume = {51}, number = {10}, pages = {1594-1604}, doi = {10.1111/imj.15520}, pmid = {34664371}, issn = {1445-5994}, support = {//Leona M. and Harry B. Helmsley Charitable Trust/ ; //National Health and Medical Research Council; Clinical investigator grant; Postgraduate scholarship/ ; }, mesh = {*Clostridioides difficile ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {The gut microbiota has a key role in the maintenance of good health, and in the pathogenesis of gastrointestinal diseases. These conditions include the inflammatory bowel diseases, colorectal cancer, coeliac disease and metabolic liver disease. Although the nature of the microbial disturbance in these conditions has not been fully characterised, this has not prevented the development of microbially based therapies. Microbial-changing therapies may address newly recognised pathophysiological contributors of disease and have the potential to replace or supplement standard therapies. Antibiotics play a role in initial Clostridiodes difficile disease and some specific inflammatory disorders. Probiotics have a more limited proven role. Faecal microbiota transplantation is of proven therapeutic benefit in recurrent C. difficile disease and ulcerative colitis. We review the current literature for microbiota-targeted therapies in gut disorders.}, }
@article {pmid34663905, year = {2021}, author = {Lai, Z and Shan, W and Li, J and Min, J and Zeng, X and Zuo, Z}, title = {Appropriate exercise level attenuates gut dysbiosis and valeric acid increase to improve neuroplasticity and cognitive function after surgery in mice.}, journal = {Molecular psychiatry}, volume = {26}, number = {12}, pages = {7167-7187}, pmid = {34663905}, issn = {1476-5578}, support = {R01 HD089999/HD/NICHD NIH HHS/United States ; R01 NS099118/NS/NINDS NIH HHS/United States ; RF1 AG061047/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Cognition ; *Cognitive Dysfunction/etiology ; *Dysbiosis ; Mice ; Mice, Inbred C57BL ; Neuronal Plasticity ; Pentanoic Acids ; *Physical Conditioning, Animal ; Surgical Procedures, Operative/*adverse effects ; }, abstract = {Postoperative cognitive dysfunction (POCD) affects the outcome of millions of patients each year. Aging is a risk factor for POCD. Here, we showed that surgery induced learning and memory dysfunction in adult mice. Transplantation of feces from surgery mice but not from control mice led to learning and memory impairment in non-surgery mice. Low intensity exercise improved learning and memory in surgery mice. Exercise attenuated surgery-induced neuroinflammation and decrease of gut microbiota diversity. These exercise effects were present in non-exercise mice receiving feces from exercise mice. Exercise reduced valeric acid, a gut microbiota product, in the blood. Valeric acid worsened neuroinflammation, learning and memory in exercise mice with surgery. The downstream effects of exercise included attenuating growth factor decrease, maintaining astrocytes in the A2 phenotypical form possibly via decreasing C3 signaling and improving neuroplasticity. Similar to these results from adult mice, exercise attenuated learning and memory impairment in old mice with surgery. Old mice receiving feces from old exercise mice had better learning and memory than those receiving control old mouse feces. Surgery increased blood valeric acid. Valeric acid blocked exercise effects on learning and memory in old surgery mice. Exercise stabilized gut microbiota, reduced neuroinflammation, attenuated growth factor decrease and preserved neuroplasticity in old mice with surgery. These results provide direct evidence that gut microbiota alteration contributes to POCD development. Valeric acid is a mediator for this effect and a potential target for brain health. Low intensity exercise stabilizes gut microbiota in the presence of insult, such as surgery.}, }
@article {pmid34662192, year = {2022}, author = {Ong, V and Wills, S and Watson, D and Sandison, T and Flanagan, S}, title = {Metabolism, Excretion, and Mass Balance of [[14]C]-Rezafungin in Animals and Humans.}, journal = {Antimicrobial agents and chemotherapy}, volume = {66}, number = {1}, pages = {e0139021}, pmid = {34662192}, issn = {1098-6596}, mesh = {Administration, Oral ; Animals ; *Antifungal Agents/therapeutic use ; Candida ; *Candidiasis, Invasive/drug therapy ; Echinocandins/therapeutic use ; Feces/chemistry ; Humans ; Rats ; }, abstract = {Rezafungin is a novel echinocandin being developed for treatment of candidemia and invasive candidiasis and for prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp. in recipients of blood and marrow transplantation. Studies using [[14]C]-radiolabeled rezafungin were conducted in rats, monkeys, and humans to characterize the mass balance, excretion, and pharmacokinetics of [[14]C]-rezafungin and to evaluate relative amounts of rezafungin metabolites compared with parent drug. Fecal excretion was the main route of elimination in rats, monkeys, and humans. Radioactivity was primarily excreted as unchanged drug, with ≥95% average total recovery in rats (through 336 h) and monkeys (through 720 h). In humans, cumulative recovery of radioactivity through the first 17 days was 52% (38% in feces, 14% in urine) with estimated mean overall recovery through day 60 of 88.3% (73% in feces, 27% in urine). The clinical pharmacokinetics of rezafungin following a single 400-mg intravenous infusion (200 μCi of [[14]C]-rezafungin) were similar in plasma, plasma total radioactivity, and whole blood total radioactivity. Unchanged rezafungin represented the majority of total radioactivity in plasma, and the partitioning of total radioactivity into red blood cells was negligible. Across species, rezafungin was primarily metabolized by hydroxylation of the terphenyl, pentyl ether side chain. In these excretion/mass balance, metabolism, and PK studies, clinical observations were consistent with findings in the rat and monkey demonstrating the minimal metabolism and slow elimination of rezafungin after intravenous administration, with fecal excretion as the major route of elimination.}, }
@article {pmid34660756, year = {2021}, author = {Yan, C and Xiao, J and Li, Z and Liu, H and Zhao, X and Liu, J and Chen, S and Zhao, X}, title = {Exogenous Fecal Microbial Transplantation Alters Fearfulness, Intestinal Morphology, and Gut Microbiota in Broilers.}, journal = {Frontiers in veterinary science}, volume = {8}, number = {}, pages = {706987}, pmid = {34660756}, issn = {2297-1769}, abstract = {Fecal microbiota transplantation (FMT) documented transplanting a donor fecal sample to a receipt individual for a desired physiologic effect. However, whether the gut microbiota construction, intestinal maturation, and behavioral plasticity are modulated by FMT during the early life of broilers is waiting for verification. To evaluate the role of transfer of fecal microbiota from aged broilers donor (BD) to another individual, 96 birds were equally divided into a check (CK, control) group and a broiler recipient (BR) group. FMT was conducted daily from 5 to 12 days of age to determine the future impact on body weight, behavior, intestinal development, and gut microbiota. Results indicated that fearfulness in the CK group was higher than the BR group in both the behavioral tests (p < 0.05). The muscularis mucosa, thickness of muscle layer, and thickness of serous membrane layer in the BR group were higher compared with those of the CK group in the jejunum (p < 0.05). In the gut microbiota, Shannon diversity showed no difference, while beta diversity presented a difference in principal coordination analysis (PCoA) between the CK and BR groups. At the phylum level, the relative abundance of Lentisphaerae in the CK group was lower than the BR (p = 0.052) and BD (p = 0.054) groups. The relative abundance of Tenericutes in the BD group was higher than that in the CK and BR groups (p < 0.05). At the genus level, Megamonas in the CK group was higher than the BR (p = 0.06) and BD (p < 0.05) groups. In the BR group, the functional capabilities of microbial communities analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were increased in the glutamatergic synapse and N-glycan biosynthesis pathways in comparison with the CK and BD groups (p < 0.05). Some characteristics of gut microbiota in the donor chickens could be transferred to recipient chickens by FMT. In conclusion, exogenous FMT as a probiotic-like administration might be an efficient way to improve the physiology and behavior of chickens. Notably, the role of microbiota for various individuals and periods remains undefined, and the mechanism of microbiota on behaviors still needs further investigation.}, }
@article {pmid34660303, year = {2021}, author = {Jasiński, M and Biliński, J and Basak, GW}, title = {The Role of the Gut Microbiome in Pathogenesis, Biology, and Treatment of Plasma Cell Dyscrasias.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {741376}, pmid = {34660303}, issn = {2234-943X}, abstract = {In response to emerging discoveries, questions are mounting as to what factors are responsible for the progression of plasma cell dyscrasias and what determines responsiveness to treatment in individual patients. Recent findings have shown close interaction between the gut microbiota and multiple myeloma cells. For instance, that malignant cells shape the composition of the gut microbiota. We discuss the role of the gut microbiota in (i) the development and progression of plasma cell dyscrasias, and (ii) the response to treatment of multiple myeloma and highlight faecal microbiota transplantation as a procedure that could modify the risk of progression or sensitize refractory malignancy to immunotherapy.}, }
@article {pmid34659541, year = {2021}, author = {Ali, H and Khurana, S and Ma, W and Peng, Y and Jiang, ZD and DuPont, H and Zhang, HC and Thomas, AS and Okhuysen, P and Wang, Y}, title = {Safety and efficacy of fecal microbiota transplantation to treat and prevent recurrent Clostridioides difficile in cancer patients.}, journal = {Journal of Cancer}, volume = {12}, number = {21}, pages = {6498-6506}, pmid = {34659541}, issn = {1837-9664}, abstract = {Background: Cancer patients are at increased risk of recurrent Clostridioides difficile infection (rCDI) due to malignancy itself, cancer therapy, and frequent antibiotic use and have a lower response rate to standard oral antibiotics. There are limited data on the safety and efficacy of fecal microbiota transplantation (FMT) for treating rCDI in cancer patients. We aim to describe our experience of using FMT to treat rCDI at a tertiary cancer center. Methods: We conducted a retrospective study of cancer patients who underwent FMT for rCDI at The University of Texas MD Anderson Cancer Center from June 2017 through January 2020. Baseline clinical data and risk factors related to rCDI and FMT were evaluated and compared between cancer types and between cases with remission and recurrence. Results: A total of 19 patients were studied: 12 with solid malignancies and 7 with hematologic malignancies. Most patients had stage IV cancer, and 21% of patients were in cancer remission. On average, patients had 2 episodes of CDI and received 3 courses of antibiotics within 1 year before FMT. 84% of patients with rCDI responded to FMT. Compared with patients who had CDI remission following FMT, non-remission cases were more likely to have received antibiotics following FMT. There were no serious adverse events or mortality within 30 days associated with FMT. Conclusions: FMT is safe, well-tolerated, and efficacious in treating rCDI in selected cancer patients. However, additional antibiotic use for complications from chemotherapy or immunosuppression negatively affected the efficacy of FMT in this population with advanced cancer.}, }
@article {pmid34652093, year = {2021}, author = {Durovic, A and Tschudin-Sutter, S}, title = {Cutting edges in Clostridioides difficile infections.}, journal = {Swiss medical weekly}, volume = {151}, number = {}, pages = {w30033}, doi = {10.4414/smw.2021.w30033}, pmid = {34652093}, issn = {1424-3997}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Child ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/drug therapy/epidemiology ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {Clostridioides difficile is the most common cause of hospital-acquired diarrhoea and one of the most important causes of hospital-acquired infections. It results in significant morbidity, mortality and economic burden - especially in the context of recurrent infections. After initial antibiotic therapy of a C. difficile infection, recurrence occurs in about 20% of all patients, which increases the risk of further recurrence to about 45%. Traditional therapeutic options for treatment of C. difficile infection include metronidazole or vancomycin. Newer therapy options such as fidaxomicin, the administration of monoclonal antibodies or faecal microbiota transplantation demonstrate significant advantages over traditional therapies, particularly regarding the reduction of the recurrence rate. This article highlights the main differences between the recommendations of the Swiss Society for Infectious Diseases on the management of "Clostridioides difficile infection" and the IDSA/SHEA reference guideline "Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)" and discusses some important challenges in -treatment of C. difficile.}, }
@article {pmid34650107, year = {2021}, author = {Jang, HM and Kim, JK and Joo, MK and Shin, YJ and Lee, CK and Kim, HJ and Kim, DH}, title = {Transplantation of fecal microbiota from patients with inflammatory bowel disease and depression alters immune response and behavior in recipient mice.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {20406}, pmid = {34650107}, issn = {2045-2322}, mesh = {Adult ; Animals ; Anxiety/etiology ; Colitis/etiology ; Colon/metabolism ; Corticosterone/blood ; Depression/complications/etiology/*microbiology ; *Fecal Microbiota Transplantation/adverse effects ; Gastrointestinal Microbiome/*physiology ; Hippocampus/metabolism ; Humans ; *Immunity ; Inflammatory Bowel Diseases/complications/*microbiology ; Interleukin-6/blood/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Peroxidase/metabolism ; }, abstract = {Gut dysbiosis is closely associated with the occurrence of inflammatory bowel disease (IBD) and psychiatric disorder. Here, to understand the difference of gut microbiota composition and physiological effect between IBD patients with (IBD/D[+]) or without depression (IBD/D[-]), we analyzed the fecal microbiota composition of patients with IBD with (/D[+]) or without depression (/D[-]) and healthy volunteers (HVs) and examined the effects of these fecal microbiota transplantations (FMTs) on the occurrence of systemic inflammation and anxiety/depression in mice. FMTs from patients with IBD/D[+] or IBD/D[-] caused IBD-like colitis in the transplanted mice: they increased the myeloperoxidase activity, IL-1β and IL-6 expression, and NF-κB[+]/CD11c[+] cell population in the colon. Transplantation of the IBD/D[+] patient feces (IBD/D[+]-F) caused IBD-like colitis more strongly than that of IBD/D[-]-F. FMTs from patients with IBD/D[+] also caused anxiety-/depression-like behaviors, increased the NF-κB[+]/Iba1[+] and lipopolysaccharide (LPS)[+]/Iba1[+] cell populations, and decreased the BDNF[+]/NeuN[+] cell population in the hippocampus. They increased LPS levels in the blood. FMTs from patients with IBD/D[-] caused anxiety-like, but not depression-like, behaviors. α-/β-diversities and composition of gut microbiota in IBD-F were different from those of HV feces (HV-F). The Enterobacteriaceae and Enterococcaceae populations and LPS levels were higher in the IBD-F than in the HV-F. The Enterococcaceae population was higher in IBD/D[+]-F vs. IBD/D[-]-F. However, the transplantation of HV-F into mice previously transplanted with IBD/D[+]-F significantly reduced depression-like behaviors, NF-κB[+]/Iba1[+] and LPS[+]/Iba1[+] cell populations in the hippocampus, LPS levels in the feces and blood, and IL-1β expression in the colon. These findings suggest that the outbreak of depression/anxiety may be dependent on the systemic inflammation with a leaky gut through the gut dysbiosis-attributable overproduction of bacterial LPS and suppression of tight junction protein expression in patients with IBD.}, }
@article {pmid34647152, year = {2022}, author = {Nie, D and Fang, Q and Cheng, J and Li, B and Li, M and Wang, H and Li, C and Gui, S and Zhang, Y and Zhao, P}, title = {The intestinal flora of patients with GHPA affects the growth and the expression of PD-L1 of tumor.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {71}, number = {5}, pages = {1233-1245}, pmid = {34647152}, issn = {1432-0851}, mesh = {*Adenoma/metabolism ; Animals ; B7-H1 Antigen/genetics ; *Gastrointestinal Microbiome ; *Growth Hormone-Secreting Pituitary Adenoma/genetics/metabolism ; Humans ; Leukocytes, Mononuclear/metabolism ; Mice ; Mice, Nude ; *Pituitary Neoplasms ; Tumor Microenvironment ; }, abstract = {CONTEXT: Pituitary adenoma (PA) is a common intracranial tumor. The evidence indicates that the tumor immune microenvironment (TIME) is associated with PA and that the intestinal flora influences other tumors' growth through interacting with the TIME. However, how the intestinal microbial flora contributes to the development of PA through the immune response is unknown.<br><br>OBJECTIVE AND METHODS: Here we used high-throughput Illumina MiSeq sequencing targeting the V3-V4 region of the 16S ribosomal RNA gene to investigate the intestinal flora of patients with growth&#xa0;hormone-secreting pituitary adenoma (GHPA), nonfunctional pituitary adenoma (NFPA), and healthy controls. We determined their effects on tumor growth and the TIME. Fecal microbiota transplantation (FMT) was performed after adoptive transfer via peripheral blood mononuclear cells to tumor-bearing nude mice, which allowed the study&#xa0;of the immune response.<br><br>RESULT: We discovered differences in the structures and quantities of intestinal flora between patients with GHPA, patients with NFPA, and healthy controls. After FMT, the intestinal flora of GHPA patients promoted the growth of tumors in mouse models. The number of programmed cell death ligand 1 (PD-L1)-positive cells increased in tumor tissues as well as the extent of infiltration of CD8[+] cells. Increased numbers of CD3[+]CD8[+] cells and increased levels of sPD-L1 were detected in peripheral blood.<br><br>CONCLUSION: These findings indicated that the intestinal flora of patients with GHPA promoted tumor growth and that the immune system may mediate this change.}, }
@article {pmid34644375, year = {2022}, author = {Eshel, A and Sharon, I and Nagler, A and Bomze, D and Danylesko, I and Fein, JA and Geva, M and Henig, I and Shimoni, A and Zuckerman, T and Youngster, I and Koren, O and Shouval, R}, title = {Origins of bloodstream infections following fecal microbiota transplantation: a strain-level analysis.}, journal = {Blood advances}, volume = {6}, number = {2}, pages = {568-573}, pmid = {34644375}, issn = {2473-9537}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {*Bacteremia/etiology ; Fecal Microbiota Transplantation ; *Graft vs Host Disease ; Humans ; Immunocompromised Host ; *Microbiota ; }, abstract = {We observed high rates of bloodstream infections (BSIs) following fecal microbiota transplantation (FMT) for graft-versus-host-disease (33 events in 22 patients). To trace the BSIs' origin, we applied a metagenomic bioinformatic pipeline screening donor and recipient stool samples for bacteremia-causing strains in 13 cases. Offending strains were not detected in FMT donations. Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii could be detected in stool samples before emerging in the blood. In this largest report of BSIs post-FMT, we present an approach that may be applicable for evaluating BSI origin following microbiota-based interventions. Our findings support FMT safety in immunocompromised patients but do not rule out FMT as an inducer of bacterial translocation.}, }
@article {pmid34644194, year = {2022}, author = {Kang, L and Tang, W and Zhang, Y and Zhang, M and Liu, J and Li, Y and Kong, S and Zhao, D and Yu, S}, title = {The gut microbiome modulates nitroglycerin-induced migraine-related hyperalgesia in mice.}, journal = {Cephalalgia : an international journal of headache}, volume = {42}, number = {6}, pages = {490-499}, doi = {10.1177/03331024211050036}, pmid = {34644194}, issn = {1468-2982}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; Hyperalgesia/chemically induced ; Mice ; *Migraine Disorders/chemically induced/metabolism ; Nitroglycerin/adverse effects ; Pain ; }, abstract = {BACKGROUND: Gut microbiota disturbance is increasingly suggested to be involved in the pathogenesis of migraine but this connection remains unsubstantiated. This study aimed to investigate whether the gut microbiome influences migraine-related hyperalgesia.<br><br>METHODS: Nitroglycerin-induced hyperalgesia was evaluated in mice with different gut microbiota statuses as follows: Specific pathogen-free mice; germ-free mice; specific pathogen-free mice treated with antibiotics to deplete the gut microbiome (ABX mice); and germ-free mice transplanted with the gut microbial profile from specific pathogen-free mice (GFC mice). Moreover, nitroglycerin-induced hyperalgesia was compared between recipient mice transplanted with gut microbiota from a patient with migraine and those that received gut microbiota from a sex- and age-matched healthy control.<br><br>RESULTS: In specific pathogen-free mice, a decreased mechanical threshold in the hind paw, increased grooming time, increased c-Fos expression level and decreased calcitonin gene-related peptide expression level as well as increased tumor necrosis factor-&#x3b1; concentration in the trigeminal nucleus caudalis were observed after nitroglycerin administration compared with saline treatment. However, increased basal sensitivity and higher basal concentrations of TNF-&#x3b1; in the trigeminal nucleus caudalis were observed in germ-free and ABX mice, while no significant difference in hyperalgesia was observed between the nitroglycerin group and saline group in germ-free and ABX mice. Moreover, significant hyperalgesia was induced by nitroglycerin administration in GFC mice. The mice transplanted with the gut microbial profile from a patient with migraine had more severe nitroglycerin-induced hyperalgesia than the mice receiving microbiota from a matched healthy control.<br><br>CONCLUSION: Our findings highlight the involvement of the gut microbiome in normal mechanical pain sensation and pathogenesis of migraine.}, }
@article {pmid34638430, year = {2021}, author = {Oldenburg, M and Rüchel, N and Janssen, S and Borkhardt, A and Gössling, KL}, title = {The Microbiome in Childhood Acute Lymphoblastic Leukemia.}, journal = {Cancers}, volume = {13}, number = {19}, pages = {}, pmid = {34638430}, issn = {2072-6694}, support = {428917761//Deutsche Forschungsgemeinschaft/ ; 2020-24//Research Committee of the Heinrich Heine University Duesseldorf/ ; }, abstract = {For almost 30 years, the term "holobiont" has referred to an ecological unit where a host (e.g., human) and all species living in or around it are considered together. The concept highlights the complex interactions between the host and the other species, which, if disturbed may lead to disease and premature aging. Specifically, the impact of microbiome alterations on the etiology of acute lymphoblastic leukemia (ALL) in children is not fully understood, but has been the focus of much research in recent years. In ALL patients, significant reductions in microbiome diversity are already observable at disease onset. It remains unclear whether such alterations at diagnosis are etiologically linked with leukemogenesis or simply due to immunological alteration preceding ALL onset. Regardless, all chemotherapeutic treatment regimens severely affect the microbiome, accompanied by severe side effects, including mucositis, systemic inflammation, and infection. In particular, dominance of Enterococcaceae is predictive of infections during chemotherapy. Long-term dysbiosis, like depletion of Faecalibacterium, has been observed in ALL survivors. Modulation of the microbiome (e.g., by fecal microbiota transplant, probiotics, or prebiotics) is currently being researched for potential protective effects. Herein, we review the latest microbiome studies in pediatric ALL patients.}, }
@article {pmid34638308, year = {2021}, author = {Oh, B and Boyle, F and Pavlakis, N and Clarke, S and Eade, T and Hruby, G and Lamoury, G and Carroll, S and Morgia, M and Kneebone, A and Stevens, M and Liu, W and Corless, B and Molloy, M and Kong, B and Libermann, T and Rosenthal, D and Back, M}, title = {The Gut Microbiome and Cancer Immunotherapy: Can We Use the Gut Microbiome as a Predictive Biomarker for Clinical Response in Cancer Immunotherapy?.}, journal = {Cancers}, volume = {13}, number = {19}, pages = {}, pmid = {34638308}, issn = {2072-6694}, abstract = {Background: Emerging evidence suggests that gut microbiota influences the clinical response to immunotherapy. This review of clinical studies examines the relationship between gut microbiota and immunotherapy outcomes. Method: A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for "cancer" and "immunotherapy/immune checkpoint inhibitor" and "microbiome/microbiota" and/or "fecal microbiome transplant FMT". The relevant literature was selected for this article. Results: Ten studies examined patients diagnosed with advanced metastatic melanoma (n = 6), hepatocellular carcinoma (HCC) (n = 2), non-small cell lung carcinoma (NSCLC) (n = 1) and one study examined combination both NSCLC and renal cell carcinoma (RCC) (n = 1). These studies consistently reported that the gut microbiome profile prior to administering immune checkpoint inhibitors (ICIs) was related to clinical response as measured by progression-free survival (PFS) and overall survival (OS). Two studies reported that a low abundance of Bacteroidetes was associated with colitis. Two studies showed that patients with anti-PD-1 refractory metastatic melanoma experienced improved response rates and no added toxicity when receiving fecal microbiota transplant (FMT) from patients with anti-PD-1 responsive disease. Conclusions: Overall, significant differences in the diversity and composition of the gut microbiome were identified in ICIs responders and non-responders. Our findings provide new insights into the value of assessing the gut microbiome in immunotherapy. Further robust randomized controlled trials (RCTs) examining the modulatory effects of the gut microbiome and FMT on ICIs in patients not responding to immunotherapy are warranted.}, }
@article {pmid34636363, year = {2022}, author = {Bilsen, MP and Lambregts, MMC and van Prehn, J and Kuijper, EJ}, title = {Faecal microbiota replacement to eradicate antimicrobial resistant bacteria in the intestinal tract - a systematic review.}, journal = {Current opinion in gastroenterology}, volume = {38}, number = {1}, pages = {15-25}, pmid = {34636363}, issn = {1531-7056}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacteria ; *Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; }, abstract = {PURPOSE OF REVIEW: Antimicrobial resistance is a rising threat to global health and is associated with increased mortality. Intestinal colonisation with multidrug-resistant organisms (MDRO) can precede invasive infection and facilitates spread within communities and hospitals. Novel decolonisation strategies, such as faecal microbiota transplantation (FMT), are being explored. The purpose of this review is to provide an update on how the field of FMT for MDRO decolonisation has developed during the past year and to assess the efficacy of FMT for intestinal MDRO decolonisation.<br><br>RECENT FINDINGS: Since 2020, seven highly heterogenous, small, nonrandomised cohort studies and five case reports have been published. In line with previous literature, decolonisation rates ranged from 20 to 90% between studies and were slightly higher for carbapenem-resistant Enterobacteriaceae than vancomycin-resistant Enterococcus. Despite moderate decolonisation rates in two studies, a reduction in MDRO bloodstream and urinary tract infections was observed.<br><br>SUMMARY AND IMPLICATIONS: Although a number of smaller cohort studies show some effect of FMT for MDRO decolonisation, questions remain regarding the true efficacy of FMT (taking spontaneous decolonisation into account), the optimal route of administration, the role of antibiotics pre and post-FMT and the efficacy in different patient populations. The observed decrease in MDRO infections post-FMT warrants further research.}, }
@article {pmid34634946, year = {2021}, author = {Mo, Q and Liu, T and Fu, A and Ruan, S and Zhong, H and Tang, J and Zhao, M and Li, Y and Zhu, S and Cai, H and Feng, F}, title = {Novel Gut Microbiota Patterns Involved in the Attenuation of Dextran Sodium Sulfate-Induced Mouse Colitis Mediated by Glycerol Monolaurate via Inducing Anti-inflammatory Responses.}, journal = {mBio}, volume = {12}, number = {5}, pages = {e0214821}, pmid = {34634946}, issn = {2150-7511}, mesh = {Animals ; Anti-Inflammatory Agents/*administration &amp; dosage ; Bacteria/classification/genetics/isolation &amp; purification ; Colitis/chemically induced/*drug therapy/immunology/*microbiology ; Cytokines/genetics/immunology ; *Gastrointestinal Microbiome/drug effects ; Humans ; Laurates/*administration &amp; dosage ; Male ; Mice ; Mice, Inbred C57BL ; Monoglycerides/*administration &amp; dosage ; Sulfates/*adverse effects ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Inflammatory bowel disease (IBD) is a type of immune-mediated chronic and relapsing inflammatory gastrointestinal symptoms. IBD cannot be completely cured because of the complex pathogenesis. Glycerol monolaurate (GML), naturally found in breast milk and coconut oil, has excellent antimicrobial, anti-inflammatory, and immunoregulatory functions. Here, the protective effect of GML on dextran sodium sulfate (DSS)-induced mouse colitis and the underlying gut microbiota-dependent mechanism were assessed in C57BL/6 mice pretreated or cotreated with GML and in antibiotic-treated mice transplanted with GML-modulated microbiota. Results showed that GML pretreatment has an advantage over GML cotreatment in alleviating weight loss and reducing disease activity index (DAI), colonic histological scores, and proinflammatory responses. Moreover, the amounts of Lactobacillus and Bifidobacterium and fecal propionic acid and butyric acid were elevated only in mice pretreated with GML upon DSS induction. Of note, fecal microbiota transplantation (FMT) from GML-pretreated mice achieved faster and more significant remission of DSS-induced colitis, manifested as reduced DAI, longer colon, decreased histological scores, and enhanced colonic Foxp3[+] regulatory T cells (Tregs) and ratio of serum anti-inflammatory/proinflammatory cytokines, as well as the reconstruction of microbial communities, including elevated Helicobacter ganmani and decreased pathogenic microbes. In conclusion, GML-mediated enhancement of Bifidobacterium and fecal short-chain fatty acids (SCFAs) could be responsible for the anticolitis effect. FMT assay confirmed that gut microbiota modulated by GML was more resistant to DSS-induced colitis via elevating beneficial H. ganmani and establishing Treg tolerant phenotype. Importantly, colitis remission induced by GML is associated with novel gut microbiota patterns, even though different microbial contexts were involved. IMPORTANCE The gut microbiota, which can be highly and dynamically affected by dietary components, is closely related to IBD pathogenesis. Here, we demonstrated that food-grade glycerol monolaurate (GML)-mediated enhancement of Bifidobacterium and fecal SCFAs could be responsible for the anticolitis effect. FMT assay confirmed that gut microbiota modulated by GML was more resistant to DSS-induced colitis via elevating beneficial H. ganmani and establishing Treg tolerant phenotype. Collectively, colitis remission induced by GML is associated with novel gut microbiota patterns, even though different microbial contexts were involved, which further provided a perspective to identify specific microbial members and those responsible for the anticolitis effect, such as Bifidobacterium and Helicobacter.}, }
@article {pmid34631742, year = {2021}, author = {Kronborg, TM and Ytting, H and Hobolth, L and Møller, S and Kimer, N}, title = {Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {718896}, pmid = {34631742}, issn = {2296-858X}, abstract = {Liver cirrhosis is a disease characterised by multiple complications and a poor prognosis. The prevalence is increasing worldwide. Chronic inflammation is ongoing in liver cirrhosis. No cure for the inflammation is available, and the current treatment of liver cirrhosis is only symptomatic. However, several different medical agents have been suggested as potential healing drugs. The majority are tested in rodents, but few human trials are effectuated. This review focuses on medical agents described in the literature with supposed alleviating and curing effects on liver cirrhosis. Twelve anti-inflammatory, five antioxidative, and three drugs with effects on gut microflora and the LPS pathway were found. Two drugs not categorised by the three former categories were found in addition. In total, 42 rodent studies and seven human trials were found. Promising effects of celecoxib, aspirin, curcumin, kahweol, pentoxifylline, diosmin, statins, emricasan, and silymarin were found in cirrhotic rodent models. Few indices of effects of etanercept, glycyrrhizin arginine salt, and mitoquinone were found. Faecal microbiota transplantation is in increasing searchlight with a supposed potential to alleviate cirrhosis. However, human trials are in demand to verify the findings in this review.}, }
@article {pmid34631604, year = {2021}, author = {Gai, X and Wang, H and Li, Y and Zhao, H and He, C and Wang, Z and Zhao, H}, title = {Fecal Microbiota Transplantation Protects the Intestinal Mucosal Barrier by Reconstructing the Gut Microbiota in a Murine Model of Sepsis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {736204}, pmid = {34631604}, issn = {2235-2988}, mesh = {Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa ; Mice ; *Sepsis/therapy ; }, abstract = {The gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies have shown that the gut flora was significantly altered in critically ill patients. This study aimed to observe what kind of GM dysbiosis is in the early stage of sepsis and whether the application of fecal microbiota transplantation (FMT) can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. The study investigated the effect of FMT on gut microbiota, mucosal barrier function, inflammatory response, and survival in a murine model of sepsis established by cecal ligation and puncture (CLP). It is found that FMT can not only reduce morbidity and mortality and restore the abundance and diversity of the gut flora in septic mice, but can also improve the intestinal barrier function by reducing epithelial cell apoptosis, improving the composition of the mucus layer, upregulating the expression of tight junction proteins, and reducing intestinal permeability and the inflammatory response. After FMT, Lachnospiraceae contributed the most to intestinal protection through enhancement of the L-lysine fermentation pathway. FMT offers a microbe-mediated survival advantage in a murine model of sepsis. Therefore, an improved understanding of the connection between microbiota, and systemic illness may yield new therapeutic strategies for patients with sepsis.}, }
@article {pmid34627951, year = {2021}, author = {Shao, X and Sun, S and Zhou, Y and Wang, H and Yu, Y and Hu, T and Yao, Y and Zhou, C}, title = {Bacteroides fragilis restricts colitis-associated cancer via negative regulation of the NLRP3 axis.}, journal = {Cancer letters}, volume = {523}, number = {}, pages = {170-181}, doi = {10.1016/j.canlet.2021.10.002}, pmid = {34627951}, issn = {1872-7980}, mesh = {Animals ; Bacteroides fragilis/*physiology ; Butyrates/pharmacology ; Colitis, Ulcerative/*complications ; Colitis-Associated Neoplasms/*prevention &amp; control ; Dysbiosis ; Fatty Acids, Volatile/metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Macrophages/drug effects/physiology ; Male ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/*physiology ; }, abstract = {Patients with persistent ulcerative colitis (UC) are at a higher risk of developing colitis-associated cancer (CAC). Previous studies have reported that intestinal microbiota disturbance plays an important role in the process of CAC development in patients with UC, indicating that targeted intervention of intestinal microbiota and its metabolites may be a potential therapeutic strategy. Gut microbiota in the process of colorectal cancer development in UC patients was analyzed using the gutMEGA database and verified in fecal samples. The abundance of Bacteroides fragilis reduced significantly in the process of colitis associated cancer development. Broad-spectrum antibiotics (BSAB) intervene with the intestinal microbiota of mice and accelerate the process of colon cancer development. However, gavage transplantation with B. fragilis can effectively reverse the effects of BSAB. In the intestinal tract, B. fragilis promotes the secretion of short-chain fatty acids (SCFAs). Subsequently, SCFAs, especially butyrate, negatively regulate the inflammatory signaling pathway mediated by NLRP3 to inhibit the activation of macrophages and the secretion of proinflammatory mediators such as IL-18 and IL-1β, reducing the level of intestinal inflammation and restricting CAC development. In conclusion, colonization with B. fragilis has been shown to be effective in ameliorating intestinal epithelial damage caused by chronic inflammation and preventing the development of colonic tumors. Thus, it can be a therapeutic intervention strategy with good clinical application prospects.}, }
@article {pmid34627858, year = {2022}, author = {Brusilovsky, M and Bao, R and Rochman, M and Kemter, AM and Nagler, CR and Rothenberg, ME}, title = {Host-Microbiota Interactions in the Esophagus During Homeostasis and Allergic Inflammation.}, journal = {Gastroenterology}, volume = {162}, number = {2}, pages = {521-534.e8}, pmid = {34627858}, issn = {1528-0012}, support = {P30 CA014599/CA/NCI NIH HHS/United States ; P30 DK078392/DK/NIDDK NIH HHS/United States ; R01 AI146099/AI/NIAID NIH HHS/United States ; R01 AI045898/AI/NIAID NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Bifidobacterium/genetics ; Cell Adhesion Molecules/genetics ; Dysbiosis/genetics/metabolism/*microbiology/pathology ; Eosinophilic Esophagitis/genetics/metabolism/*microbiology/pathology ; Esophageal Mucosa/metabolism/microbiology/pathology ; Esophagus/metabolism/*microbiology/pathology ; Firmicutes/genetics ; Gene Expression ; Gene Expression Profiling ; Homeostasis ; Host Microbial Interactions/*physiology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Kallikreins/genetics ; Lactobacillales/genetics ; Mice ; RNA, Ribosomal, 16S/genetics ; RNA-Seq ; }, abstract = {BACKGROUND &amp; AIMS: Microbiota composition and mechanisms of host-microbiota interactions in the esophagus are unclear. We aimed to uncover fundamental information about the esophageal microbiome and its potential significance to eosinophilic esophagitis (EoE).<br><br>METHODS: Microbiota composition, transplantation potential, and antibiotic responsiveness in the esophagus were established via 16S ribosomal RNA sequencing. Functional outcomes of microbiota colonization were assessed by RNA sequencing analysis of mouse esophageal epithelium and compared with the human EoE transcriptome. The impact of dysbiosis was assessed using a preclinical model of EoE.<br><br>RESULTS: We found that the murine esophagus is colonized with diverse microbial communities within the first month of life. The esophageal microbiota is distinct, dominated by Lactobacillales, and demonstrates spatial heterogeneity as the proximal and distal esophagus are enriched in Bifidobacteriales and Lactobacillales, respectively. Fecal matter transplantation restores the esophageal microbiota, demonstrating that the local environment drives diversity. Microbiota colonization modifies esophageal tissue morphology and gene expression that is enriched in pathways associated with epithelial barrier function and overlapping with genes involved in EoE, including POSTN, KLK5, and HIF1A. Finally, neonatal antibiotic treatment reduces the abundance of Lactobacillales and exaggerates type 2 inflammation in the esophagus. Clinical data substantiated loss of esophageal Lactobacillales in EoE compared with controls.<br><br>CONCLUSIONS: The esophagus has a unique microbiome with notable differences between its proximal and distal regions. Fecal matter transplantation restores the esophageal microbiome. Antibiotic-induced dysbiosis exacerbates disease in a murine model of EoE. Collectively, these data establish the composition, transplantation potential, antibiotic responsiveness, and host-microbiota interaction in the esophagus and have implications for gastrointestinal health and disease.}, }
@article {pmid34627158, year = {2021}, author = {Shimizu, H and Arai, K and Asahara, T and Takahashi, T and Tsuji, H and Matsumoto, S and Takeuchi, I and Kyodo, R and Yamashiro, Y}, title = {Stool preparation under anaerobic conditions contributes to retention of obligate anaerobes: potential improvement for fecal microbiota transplantation.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {275}, pmid = {34627158}, issn = {1471-2180}, mesh = {*Anaerobiosis ; Bacteria, Anaerobic/*physiology ; Fecal Microbiota Transplantation/*methods/*standards ; Feces/*microbiology ; Humans ; RNA, Ribosomal, 16S/genetics ; RNA, Ribosomal, 23S/genetics ; Specimen Handling/*methods ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) in patients with ulcerative colitis has shown variable efficacy depending on the protocol used. A previous randomized controlled trial reported that anaerobic preparation of donor stool contributes to improved efficacy. Despite the suggestion that viable obligate anaerobes would be decreased through aerobic handling, there have been only a limited number of reports on how these aerobic or anaerobic procedures affect the composition of viable microbiota in the fecal slurries used for FMT.<br><br>METHODS: We adopted 16S and 23S rRNA-targeted reverse transcription-quantitative polymerase chain reaction to quantify viable bacteria in fecal slurries. This study utilized specific primers designed to detect obligate anaerobes (including Clostridium coccoides group, C. leptum subgroup, Bacteroides fragilis group, Bifidobacterium, Atopobium cluster, and Prevotella) and facultative anaerobes (including total lactobacilli, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus). We then calculated the ratio change (RC) between before and after mixing, and compared the resulting values between anaerobic-prep and aerobic-prep in samples fixed immediately after blending (RCAn0 vs. RCAe0) and in samples maintained (under anaerobic or aerobic conditions) for 1&#x2009;h after blending (RCAn1 vs. RCAe1).<br><br>RESULTS: For most obligate anaerobes, the median RC tended to be less than 1, indicating that the number of obligate anaerobes was decreased by the blending procedure. However, in samples maintained for 1&#x2009;h after blending, anaerobic-prep counteracted the decrease otherwise seen for the C. coccoides group and B. fragilis groups (P&#x2009;<&#x2009;0.01 for both). The C. leptum subgroup also tended to show higher RC by anaerobic-prep than by aerobic-prep, although this effect was not statistically significant. Among facultative anaerobes, Enterobacteriaceae, Enterococcus, and Staphylococcus showed median RC values of more than 1, indicating that these organisms survived and even grew after mixing. Moreover, oxygen exposure had no significant influence on the survival of the facultative anaerobes.<br><br>CONCLUSIONS: The conditions under which the blending procedure was performed affected the proportion of live anaerobes in fecal slurries. The obligate anaerobes tended to be decreased by blending processes, but anaerobic-prep significantly mitigated this effect. Anaerobic-prep may improve the efficacy of FMT by permitting the efficient transfer of obligate anaerobes to patients with ulcerative colitis.}, }
@article {pmid34624222, year = {2021}, author = {Lam, KC and Araya, RE and Huang, A and Chen, Q and Di Modica, M and Rodrigues, RR and Lopès, A and Johnson, SB and Schwarz, B and Bohrnsen, E and Cogdill, AP and Bosio, CM and Wargo, JA and Lee, MP and Goldszmid, RS}, title = {Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment.}, journal = {Cell}, volume = {184}, number = {21}, pages = {5338-5356.e21}, pmid = {34624222}, issn = {1097-4172}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; ZIA BC011670/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Akkermansia/drug effects/physiology ; Animals ; Dendritic Cells/drug effects/metabolism ; Dietary Fiber/pharmacology ; Dinucleoside Phosphates/administration &amp; dosage/pharmacology ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immunomodulation/drug effects ; Interferon Type I/*metabolism ; Killer Cells, Natural/drug effects/metabolism ; Macrophages/drug effects/metabolism ; Melanoma/immunology/pathology ; Membrane Proteins/*metabolism ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; *Microbiota/drug effects ; Monocytes/drug effects/*metabolism ; Phagocytes/drug effects/metabolism ; Transcription, Genetic/drug effects ; *Tumor Microenvironment/drug effects ; Mice ; }, abstract = {The tumor microenvironment (TME) influences cancer progression and therapy response. Therefore, understanding what regulates the TME immune compartment is vital. Here we show that microbiota signals program mononuclear phagocytes in the TME toward immunostimulatory monocytes and dendritic cells (DCs). Single-cell RNA sequencing revealed that absence of microbiota skews the TME toward pro-tumorigenic macrophages. Mechanistically, we show that microbiota-derived stimulator of interferon genes (STING) agonists induce type I interferon (IFN-I) production by intratumoral monocytes to regulate macrophage polarization and natural killer (NK) cell-DC crosstalk. Microbiota modulation with a high-fiber diet triggered the intratumoral IFN-I-NK cell-DC axis and improved the efficacy of immune checkpoint blockade (ICB). We validated our findings in individuals with melanoma treated with ICB and showed that the predicted intratumoral IFN-I and immune compositional differences between responder and non-responder individuals can be transferred by fecal microbiota transplantation. Our study uncovers a mechanistic link between the microbiota and the innate TME that can be harnessed to improve cancer therapies.}, }
@article {pmid34623758, year = {2021}, author = {Yau, YK and Mak, WYJ and Lui, NSR and Ng, WYR and Cheung, CYK and Li, YLA and Ching, YLJ and Chin, ML and Lau, HSL and Chan, KLF and Chan, KSP and Ng, SC}, title = {High prevalence of extended-spectrum beta-lactamase organisms and the COVID-19 pandemic impact on donor recruitment for fecal microbiota transplantation in Hong Kong.}, journal = {United European gastroenterology journal}, volume = {9}, number = {9}, pages = {1027-1038}, pmid = {34623758}, issn = {2050-6414}, mesh = {Adolescent ; Adult ; COVID-19 ; *Donor Selection ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Hong Kong ; Humans ; Male ; Middle Aged ; Pandemics ; Prevalence ; Young Adult ; beta-Lactamases ; }, abstract = {BACKGROUND: With increasing number of clinical trials relating to fecal microbiota transplantation (FMT), it is crucial to identify and recruit long-term, healthy, and regular fecal donors.<br><br>OBJECTIVE: We aimed to report the outcomes of screening and recruitment of fecal donors for FMT.<br><br>METHODS: Potential donors were recruited via advertisement through internal mass emails at a university. They were required to undergo a pre-screening telephone interview, a detailed questionnaire, followed by blood and stool investigations.<br><br>RESULTS: From January 2017 to December 2020, 119 potential donors were assessed with 75 failed pre-screening. Reasons for failure included: inability to come back for regular and long-term donation (n&#xa0;=&#xa0;19), high body mass index (n&#xa0;=&#xa0;17), underlying chronic illness or on long-term medications (n&#xa0;=&#xa0;11), being healthcare professionals (n&#xa0;=&#xa0;10), use of antibiotics within 3&#xa0;months (n&#xa0;=&#xa0;5) and others (n&#xa0;=&#xa0;13). Forty-four donors completed questionnaires and 11 did not fulfill the clinical criteria. Of the remaining 33 potential donors who had stool and blood tests, 21 failed stool investigations (19 extended-spectrum beta-lactamase [ESBL] organisms, one Clostridioides difficile, one C. difficile plus Methicillin Resistant Staphylococcus aureus), one failed blood tests (high serum alkaline phosphatase level), one required long-term medication and nine withdrew consent and/or lost to follow-up. In total, only one out of 119 (0.8%) potential donors was successfully recruited as a regular donor.<br><br>CONCLUSION: There was a high failure rate in donor screening for FMT. Main reasons for screening failure included high prevalence of positive ESBL organisms in stool and failed commitment to regular stool donation.}, }
@article {pmid34622239, year = {2021}, author = {Hanssen, NMJ and Nieuwdorp, M}, title = {Fecal microbiota transplantation and fiber supplementation, better together?.}, journal = {Cell reports. Medicine}, volume = {2}, number = {9}, pages = {100403}, pmid = {34622239}, issn = {2666-3791}, mesh = {Dietary Supplements ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Insulin Resistance ; *Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) is emerging as a tool to study the microbiome and as a potential treatment for several non-infectious diseases. Recently, Mocanu et al. showed that supplementing low fermentable fiber after FMT may improve insulin sensitivity in severely obese individuals.[1].}, }
@article {pmid34622234, year = {2021}, author = {Ahmed, BA and Ong, FJ and Barra, NG and Blondin, DP and Gunn, E and Oreskovich, SM and Szamosi, JC and Syed, SA and Hutchings, EK and Konyer, NB and Singh, NP and Yabut, JM and Desjardins, EM and Anhê, FF and Foley, KP and Holloway, AC and Noseworthy, MD and Haman, F and Carpentier, AC and Surette, MG and Schertzer, JD and Punthakee, Z and Steinberg, GR and Morrison, KM}, title = {Lower brown adipose tissue activity is associated with non-alcoholic fatty liver disease but not changes in the gut microbiota.}, journal = {Cell reports. Medicine}, volume = {2}, number = {9}, pages = {100397}, pmid = {34622234}, issn = {2666-3791}, support = {FDN-154295//CIHR/Canada ; 201709FDN-CEBA-116200//CIHR/Canada ; }, mesh = {Adipose Tissue, Brown/*pathology ; Adiposity ; Adolescent ; Adult ; Animals ; Cold Temperature ; Female ; *Gastrointestinal Microbiome ; Homeostasis ; Humans ; Male ; Mice, Inbred C57BL ; Middle Aged ; Multivariate Analysis ; Non-alcoholic Fatty Liver Disease/*microbiology/*pathology ; Young Adult ; Mice ; }, abstract = {In rodents, lower brown adipose tissue (BAT) activity is associated with greater liver steatosis and changes in the gut microbiome. However, little is known about these relationships in humans. In adults (n = 60), we assessed hepatic fat and cold-stimulated BAT activity using magnetic resonance imaging and the gut microbiota with 16S sequencing. We transplanted gnotobiotic mice with feces from humans to assess the transferability of BAT activity through the microbiota. Individuals with NAFLD (n = 29) have lower BAT activity than those without, and BAT activity is inversely related to hepatic fat content. BAT activity is not related to the characteristics of the fecal microbiota and is not transmissible through fecal transplantation to mice. Thus, low BAT activity is associated with higher hepatic fat accumulation in human adults, but this does not appear to have been mediated through the gut microbiota.}, }
@article {pmid34621688, year = {2021}, author = {Bokoliya, SC and Dorsett, Y and Panier, H and Zhou, Y}, title = {Procedures for Fecal Microbiota Transplantation in Murine Microbiome Studies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {711055}, pmid = {34621688}, issn = {2235-2988}, support = {R01 NS102633/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Mice ; *Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) has been widely recognized as an approach to determine the microbiome's causal role in gut dysbiosis-related disease models and as a novel disease-modifying therapy. Despite potential beneficial FMT results in various disease models, there is a variation and complexity in procedural agreement among research groups for performing FMT. The viability of the microbiome in feces and its successful transfer depends on various aspects of donors, recipients, and lab settings. This review focuses on the technical practices of FMT in animal studies. We first document crucial factors required for collecting, handling, and processing donor fecal microbiota for FMT. Then, we detail the description of gut microbiota depletion methods, FMT dosages, and routes of FMT administrations in recipients. In the end, we describe assessments of success rates of FMT with sustainability. It is critical to work under the anaerobic condition to preserve as much of the viability of bacteria. Utilization of germ- free mice or depletion of recipient gut microbiota by antibiotics or polyethylene glycol are two common recipient preparation approaches to achieve better engraftment. Oral-gastric gavage preferred by most researchers for fast and effective administration of FMT in mice. Overall, this review highlights various methods that may lead to developing the standard and reproducible protocol for FMT.}, }
@article {pmid34618582, year = {2021}, author = {Pernigoni, N and Zagato, E and Calcinotto, A and Troiani, M and Mestre, RP and Calì, B and Attanasio, G and Troisi, J and Minini, M and Mosole, S and Revandkar, A and Pasquini, E and Elia, AR and Bossi, D and Rinaldi, A and Rescigno, P and Flohr, P and Hunt, J and Neeb, A and Buroni, L and Guo, C and Welti, J and Ferrari, M and Grioni, M and Gauthier, J and Gharaibeh, RZ and Palmisano, A and Lucchini, GM and D'Antonio, E and Merler, S and Bolis, M and Grassi, F and Esposito, A and Bellone, M and Briganti, A and Rescigno, M and Theurillat, JP and Jobin, C and Gillessen, S and de Bono, J and Alimonti, A}, title = {Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis.}, journal = {Science (New York, N.Y.)}, volume = {374}, number = {6564}, pages = {216-224}, doi = {10.1126/science.abf8403}, pmid = {34618582}, issn = {1095-9203}, mesh = {Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use ; Androgens/*biosynthesis ; Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects/genetics/*metabolism ; Cell Line, Tumor ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/genetics/*physiology ; *Host Microbial Interactions ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Neoplasms, Experimental ; Prevotella/metabolism ; Prostatic Neoplasms, Castration-Resistant/drug therapy/*metabolism/*microbiology ; Symbiosis ; Xenograft Model Antitumor Assays ; }, abstract = {The microbiota comprises the microorganisms that live in close contact with the host, with mutual benefit for both counterparts. The contribution of the gut microbiota to the emergence of castration-resistant prostate cancer (CRPC) has not yet been addressed. We found that androgen deprivation in mice and humans promotes the expansion of defined commensal microbiota that contributes to the onset of castration resistance in mice. Specifically, the intestinal microbial community in mice and patients with CRPC was enriched for species capable of converting androgen precursors into active androgens. Ablation of the gut microbiota by antibiotic therapy delayed the emergence of castration resistance even in immunodeficient mice. Fecal microbiota transplantation (FMT) from CRPC mice and patients rendered mice harboring prostate cancer resistant to castration. In contrast, tumor growth was controlled by FMT from hormone-sensitive prostate cancer patients and Prevotella stercorea administration. These results reveal that the commensal gut microbiota contributes to endocrine resistance in CRPC by providing an alternative source of androgens.}, }
@article {pmid34617582, year = {2021}, author = {Real-López, M and Peraire, M and Ramos-Vidal, C and Nath, D and Hervás, A and Cortés, X}, title = {[Involvement of intestinal dysbiosis in the etiopathogenesis and treatment of autism spectrum disorder: a bibliographic review].}, journal = {Revista de neurologia}, volume = {73}, number = {8}, pages = {282-295}, doi = {10.33588/rn.7308.2021189}, pmid = {34617582}, issn = {1576-6578}, mesh = {Autism Spectrum Disorder/*etiology/*therapy ; Dysbiosis/*complications ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {INTRODUCTION: Autism spectrum disorder is a neurodevelopmental disorder with phenotypic heterogeneity and variable symptomatic course of partly unknown etiology. The prevalence of gastrointestinal disorders in autism leads to investigate the role that intestinal microbiota may have as a causal factor and to propose specific therapeutic interventions. The role of microbiota in brain development and function, demonstrated in animal models, justifies its investigation in this neuropsychiatric disorder.<br><br>OBJECTIVE: The aim was to investigate the relationship between altered microbiota composition and autism spectrum disorder, and to assess the therapeutic role of prebiotics, probiotics and fecal transplantation in this neurodevelopmental disorder.<br><br>DEVELOPMENT: A literature review was conducted in PubMed, Cochrane Library and Google Scholar to select relevant articles related to the topic that were published between January 2012 and April 2020. Thirty-five relevant articles were selected. In 23 of them, significant differences were found in the composition and diversity of the microbiota in children with ASD, as well as in the biomolecules involved in certain metabolic pathways. The other 12 investigations reported gastrointestinal and behavioral improvements after therapeutic intervention.<br><br>CONCLUSIONS: It is reasonable to state that there is enough evidence to support the existence of a relationship between intestinal microbiota and autism spectrum disorders. This fact should be explored in depth to assess the etiopathogenic burden of dysbiosis and the possible therapeutic tools.}, }
@article {pmid34617511, year = {2021}, author = {Ang, QY and Alba, DL and Upadhyay, V and Bisanz, JE and Cai, J and Lee, HL and Barajas, E and Wei, G and Noecker, C and Patterson, AD and Koliwad, SK and Turnbaugh, PJ}, title = {The East Asian gut microbiome is distinct from colocalized White subjects and connected to metabolic health.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34617511}, issn = {2050-084X}, support = {T32 AI060537/AI/NIAID NIH HHS/United States ; R01 DK114034/DK/NIDDK NIH HHS/United States ; T32 HL007185/HL/NHLBI NIH HHS/United States ; R01DK11230403S1/NH/NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; R01 AR074500/AR/NIAMS NIH HHS/United States ; R01DK11230401/DK/NIDDK NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/classification/*isolation &amp; purification ; Bacterial Physiological Phenomena ; California ; Asia, Eastern/ethnology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Metabolism ; *Metagenome ; Metagenomics ; San Francisco ; }, abstract = {East Asians (EAs) experience worse metabolic health outcomes compared to other ethnic groups at lower body mass indices; however, the potential role of the gut microbiota in contributing to these health disparities remains unknown. We conducted a multi-omic study of 46 lean and obese East Asian and White participants living in the San Francisco Bay Area, revealing marked differences between ethnic groups in bacterial richness and community structure. White individuals were enriched for the mucin-degrading Akkermansia muciniphila. East Asian subjects had increased levels of multiple bacterial phyla, fermentative pathways detected by metagenomics, and the short-chain fatty acid end-products acetate, propionate, and isobutyrate. Differences in the gut microbiota between the East Asian and White subjects could not be explained by dietary intake, were more pronounced in lean individuals, and were associated with current geographical location. Microbiome transplantations into germ-free mice demonstrated stable diet- and host genotype-independent differences between the gut microbiotas of East Asian and White individuals that differentially impact host body composition. Taken together, our findings add to the growing body of literature describing microbiome variations between ethnicities and provide a starting point for defining the mechanisms through which the microbiome may shape disparate health outcomes in East Asians.}, }
@article {pmid34616800, year = {2021}, author = {Bolasco, G and Capriati, T and Grimaldi, C and Monti, L and De Pasquale, MD and Patera, IP and Spada, M and Maggiore, G and Diamanti, A}, title = {Long-term outcome of pancreatic function following oncological surgery in children: Institutional experience and review of the literature.}, journal = {World journal of clinical cases}, volume = {9}, number = {25}, pages = {7340-7349}, pmid = {34616800}, issn = {2307-8960}, abstract = {BACKGROUND: Pancreatic neoplasms are uncommon in children and in most cases they are benign or have low malignant potential. Pancreatoblastoma and solid pseudopapillary tumor are the most frequent types in early and late childhood, respectively. Complete resection, although burdened by severe complications, is the only curative treatment for these diseases. Pancreatic surgery may result in impaired exocrine and endocrine pancreatic function. However, limited data are available on the long-term pediatric pancreatic function following surgical resection.<br><br>AIM: To investigate endocrine and exocrine pancreatic function and growth after oncological pancreatic surgery in a pediatric series.<br><br>METHODS: A retrospective analysis of all pediatric patients who underwent surgery for pancreatic neoplasm in our Institution from January 31, 2002 to the present was performed. Endocrine and exocrine insufficiency, auxological and fat-soluble vitamin status (A, D, E and clotting tests) were assessed at diagnosis and at every follow-up visit. Exocrine insufficiency was defined as steatorrhea with fecal elastase-1 < 200 &#xb5;g/g stool, while endocrine insufficiency was identified as onset of Diabetes or Impaired Glucose Tolerance. Growth was evaluated based on body mass index (BMI) z-score trend.<br><br>RESULTS: Sixteen patients (12 girls and 4 boys, mean age 10.7 &#xb1; 5.3 years), were included. Nine patients (56%) had a neoplasm in the pancreatic head, 4 in the body/tail, 2 in the tail and 1 in the body. Histological findings were as follows: Solid pseudopapillary tumor in 10 patients (62.5%), insulinoma in 2 patients, neuroendocrine tumor in 2 patients and acinar cell carcinoma in 2 patients. The most frequent surgery was pancreaticoduodenectomy (50%). Exocrine failure occurred in 4 patients (25%) and endocrine failure in 2 patients (12.5%). Exocrine insufficiency occurred early (within 6 mo after surgery) and endocrine insufficiency later (8 and 10 years after surgery). Mean BMI z-score was 0.36 &#xb1; 1.1 at diagnosis and 0.27 &#xb1; 0.95 at the last assessment. Vitamin D was insufficient (< 30 ng/mL) in 8 of the 16 patients during the follow-up period. Vitamins A, E and clotting test were into the normal ranges in all patients.<br><br>CONCLUSION: Careful and long-term monitoring should follow any pancreatic surgery, to recognize and promptly treat exocrine and endocrine pancreatic insufficiency, which can occur after surgery.}, }
@article {pmid34616650, year = {2021}, author = {Zhu, LB and Zhang, YC and Huang, HH and Lin, J}, title = {Prospects for clinical applications of butyrate-producing bacteria.}, journal = {World journal of clinical pediatrics}, volume = {10}, number = {5}, pages = {84-92}, pmid = {34616650}, issn = {2219-2808}, abstract = {As the major source of energy for colonic mucosal cells and as an important regulator of gene expression, inflammation, differentiation, and apoptosis in host cells, microbiota-derived butyrate can enhance the intestinal mucosal immune barrier, modulate systemic immune response, and prevent infections. Maintaining a certain level of butyrate production in the gut can help balance intestinal microbiota, regulate host immune response, and promote the development and maintenance of the intestinal mucosal barrier. Butyrate-producing bacteria act as probiotics and play important roles in a variety of normal biological functions. Bacteriotherapeutic supplementation by using fecal microbiota transplantation to restore butyrate-producing commensal bacteria in the gut has been very successful in the treatment of recurrent and refractory Clostridium difficile (C. difficile) infection or C. difficile-negative nosocomial diarrhea. Administration of probiotics that include butyrate-producing bacteria may have a role in the treatment of inflammatory bowel diseases and in the prevention of necrotizing enterocolitis and late-onset sepsis in premature infants. Furthermore, modulating gut microbiota with dietary approaches may improve intestinal dysbiosis commonly seen in patients with obesity-associated metabolic disorders. Supplementation with a butyrate-producing bacterial stain might be used to increase energy expenditure, improve insulin sensitivity, and to help control obesity and metabolic syndrome.}, }
@article {pmid34612696, year = {2021}, author = {Wang, H and Song, W and Wu, Q and Gao, X and Li, J and Tan, C and Zhou, H and Zhu, J and He, Y and Yin, J}, title = {Fecal Transplantation from db/db Mice Treated with Sodium Butyrate Attenuates Ischemic Stroke Injury.}, journal = {Microbiology spectrum}, volume = {9}, number = {2}, pages = {e0004221}, pmid = {34612696}, issn = {2165-0497}, mesh = {Animals ; Brain Infarction/*drug therapy/pathology ; Brain Injuries/*drug therapy ; Butyric Acid/*therapeutic use ; Cytokines/blood ; Diabetes Mellitus, Type 2/*pathology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Ischemic Stroke/*drug therapy/pathology ; Lipopolysaccharides/blood ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Middle Aged ; }, abstract = {The complication of type 2 diabetes (T2D) exacerbates brain infarction in acute ischemic stroke (AIS). Because butyrate-producing bacteria are decreased in T2D and butyrate has been reported to be associated with attenuated brain injury in AIS, we hypothesize that administering butyrate could ameliorate T2D-associated exacerbation of brain infarction in AIS. Therefore, we first validated that Chinese AIS patients with T2D comorbidity have significantly lower levels of fecal butyrate-producing bacteria and butyrate than AIS patients without T2D. Then, we performed a 4-week intervention in T2D mice receiving either sodium butyrate (SB) or sodium chloride (NaCl) and found that SB improved the diabetic phenotype, altered the gut microbiota, and ameliorated brain injury after stroke. Fecal samples were collected from T2D mice after SB or NaCl treatment and were transplanted into antibiotic-treated C57BL/6 mice. After 2 weeks of transplantation, the gut microbiota profile and butyrate level of recipient mice were tested, and then the recipient mice were subjected to ischemic stroke. Stroke mice that received gut microbiota from SB-treated mice had a smaller cerebral infarct volume than mice that received gut microbiota from NaCl-treated mice. This protection was also associated with improvements in gut barrier function, reduced serum levels of lipopolysaccharide (LPS), LPS binding protein (LBP), and proinflammatory cytokines, and improvements in the blood-brain barrier. IMPORTANCE Ischemic stroke is a major global health burden, and T2D is a well-known comorbidity that aggravates brain injury after ischemic stroke. However, the underlying mechanism by which T2D exacerbates stroke injury has not been completely elucidated. A large amount of evidence suggests that the gut microbiota composition affects stroke outcomes. Our results showed that the gut microbiota of T2D aggravated brain injury after ischemic stroke and could be modified by SB to afford neuroprotection against stroke injury. These findings suggest that supplementation with SB is a potential therapeutic strategy for T2D patients with ischemic stroke.}, }
@article {pmid34611619, year = {2021}, author = {Claeys, W and Van Hoecke, L and Lefere, S and Geerts, A and Verhelst, X and Van Vlierberghe, H and Degroote, H and Devisscher, L and Vandenbroucke, RE and Van Steenkiste, C}, title = {The neurogliovascular unit in hepatic encephalopathy.}, journal = {JHEP reports : innovation in hepatology}, volume = {3}, number = {5}, pages = {100352}, pmid = {34611619}, issn = {2589-5559}, abstract = {Hepatic encephalopathy (HE) is a neurological complication of hepatic dysfunction and portosystemic shunting. It is highly prevalent in patients with cirrhosis and is associated with poor outcomes. New insights into the role of peripheral origins in HE have led to the development of innovative treatment strategies like faecal microbiota transplantation. However, this broadening of view has not been applied fully to perturbations in the central nervous system. The old paradigm that HE is the clinical manifestation of ammonia-induced astrocyte dysfunction and its secondary neuronal consequences requires updating. In this review, we will use the holistic concept of the neurogliovascular unit to describe central nervous system disturbances in HE, an approach that has proven instrumental in other neurological disorders. We will describe HE as a global dysfunction of the neurogliovascular unit, where blood flow and nutrient supply to the brain, as well as the function of the blood-brain barrier, are impaired. This leads to an accumulation of neurotoxic substances, chief among them ammonia and inflammatory mediators, causing dysfunction of astrocytes and microglia. Finally, glymphatic dysfunction impairs the clearance of these neurotoxins, further aggravating their effect on the brain. Taking a broader view of central nervous system alterations in liver disease could serve as the basis for further research into the specific brain pathophysiology of HE, as well as the development of therapeutic strategies specifically aimed at counteracting the often irreversible central nervous system damage seen in these patients.}, }
@article {pmid34611194, year = {2021}, author = {Karlsen, TR and Kong, XY and Holm, S and Quiles-Jiménez, A and Dahl, TB and Yang, K and Sagen, EL and Skarpengland, T and S Øgaard, JD and Holm, K and Vestad, B and Olsen, MB and Aukrust, P and Bjørås, M and Hov, JR and Halvorsen, B and Gregersen, I}, title = {NEIL3-deficiency increases gut permeability and contributes to a pro-atherogenic metabolic phenotype.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {19749}, pmid = {34611194}, issn = {2045-2322}, mesh = {Age Factors ; Animals ; Atherosclerosis/*etiology/*metabolism/pathology ; Biomarkers ; Disease Models, Animal ; Disease Susceptibility ; Dysbiosis ; *Energy Metabolism ; Gastrointestinal Microbiome ; Genetic Predisposition to Disease ; Humans ; Immunohistochemistry ; Intestinal Mucosa/*metabolism ; Mice ; Mice, Knockout ; N-Glycosyl Hydrolases/*deficiency ; Permeability ; }, abstract = {Atherosclerosis and its consequences cause considerable morbidity and mortality world-wide. We have previously shown that expression of the DNA glycosylase NEIL3 is regulated in human atherosclerotic plaques, and that NEIL3-deficiency enhances atherogenesis in Apoe[-/-] mice. Herein, we identified a time point prior to quantifiable differences in atherosclerosis between Apoe[-/-]Neil3[-/-] mice and Apoe[-/-] mice. Mice at this age were selected to explore the metabolic and pathophysiological processes preceding extensive atherogenesis in NEIL3-deficient mice. Untargeted metabolomic analysis of young Apoe[-/-]Neil3[-/-] mice revealed significant metabolic disturbances as compared to mice expressing NEIL3, particularly in metabolites dependent on the gut microbiota. 16S rRNA gene sequencing of fecal bacterial DNA indeed confirmed that the NEIL3-deficient mice had altered gut microbiota, as well as increased circulating levels of the bacterially derived molecule LPS. The mice were challenged with a FITC-conjugated dextran to explore gut permeability, which was significantly increased in the NEIL3-deficient mice. Further, immunohistochemistry showed increased levels of the proliferation marker Ki67 in the colonic epithelium of NEIL3-deficient mice, suggesting increased proliferation of intestinal cells and gut leakage. We suggest that these metabolic alterations serve as drivers of atherosclerosis in NEIL3-deficient mice.}, }
@article {pmid34609073, year = {2021}, author = {Ubachs, J and Ziemons, J and Soons, Z and Aarnoutse, R and van Dijk, DPJ and Penders, J and van Helvoort, A and Smidt, ML and Kruitwagen, RFPM and Baade-Corpelijn, L and Olde Damink, SWM and Rensen, SS}, title = {Gut microbiota and short-chain fatty acid alterations in cachectic cancer patients.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {12}, number = {6}, pages = {2007-2021}, pmid = {34609073}, issn = {2190-6009}, mesh = {Animals ; Cachexia/epidemiology/etiology ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome ; Humans ; *Pancreatic Neoplasms ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Cancer cachexia is characterized by a negative energy balance, muscle and adipose tissue wasting, insulin resistance, and systemic inflammation. Because of its strong negative impact on prognosis and its multifactorial nature that is still not fully understood, cachexia remains an important challenge in the field of cancer treatment. Recent animal studies indicate that the gut microbiota is involved in the pathogenesis and manifestation of cancer cachexia, but human data are lacking. The present study investigates gut microbiota composition, short-chain fatty acids (SCFA), and inflammatory parameters in human cancer cachexia.<br><br>METHODS: Faecal samples were prospectively collected in patients (N&#xa0;=&#xa0;107) with pancreatic cancer, lung cancer, breast cancer, or ovarian cancer. Household partners (N&#xa0;=&#xa0;76) of the patients were included as healthy controls with similar diet and environmental conditions. Patients were classified as cachectic if they lost >5% body weight in the last 6&#xa0;months. Gut microbiota composition was analysed by sequencing of the 16S rRNA V4 gene region. Faecal SCFA levels were quantified by gas chromatography. Faecal calprotectin was assessed with enzyme-linked immunosorbent assay. Serum C-reactive protein and leucocyte counts were retrieved from medical records.<br><br>RESULTS: Cachexia prevalence was highest in pancreatic cancer (66.7%), followed by ovarian cancer (25%), lung cancer (20.8%), and breast cancer (17.3%). Microbial &#x3b1;-diversity was not significantly different between cachectic cancer patients (N&#xa0;=&#xa0;33), non-cachectic cancer patients (N&#xa0;=&#xa0;74), or healthy controls (N&#xa0;=&#xa0;76) (species richness P&#xa0;=&#xa0;0.31; Shannon effective index P&#xa0;=&#xa0;0.46). Community structure (&#x3b2;-diversity) tended to differ between these groups (P&#xa0;=&#xa0;0.053), although overall differences were subtle and no clear clustering of samples was observed. Proteobacteria (P&#xa0;<&#xa0;0.001), an unknown genus from the Enterobacteriaceae family (P&#xa0;<&#xa0;0.01), and Veillonella (P&#xa0;<&#xa0;0.001) were more abundant among cachectic cancer patients. Megamonas (P&#xa0;<&#xa0;0.05) and Peptococcus (P&#xa0;<&#xa0;0.001) also showed differential abundance. Faecal levels of all SCFA tended to be lower in cachectic cancer patients, but only acetate concentrations were significantly reduced (P&#xa0;<&#xa0;0.05). Faecal calprotectin levels were positively correlated with the abundance of Peptococcus, unknown Enterobacteriaceae, and Veillonella. We also identified several correlations and interactions between clinical and microbial parameters.<br><br>CONCLUSIONS: This clinical study provided the first insights into the alterations of gut microbiota composition and SCFA levels that occur in cachectic cancer patients and how they are related to inflammatory parameters. These results pave the way for further research examining the role of the gut microbiota in cancer cachexia and its potential use as therapeutic target.}, }
@article {pmid34608030, year = {2022}, author = {Jeney, SES and Avelar-Barragan, J and Whiteson, K and Chang, J and Dutta, S and Lane, F}, title = {Fecal Putative Uropathogen Abundance and Antibiotic Resistance Gene Carriage in Women With Refractory Recurrent Urinary Tract Infection Treated With Fecal Microbiota Transplantation.}, journal = {Female pelvic medicine &amp; reconstructive surgery}, volume = {28}, number = {4}, pages = {213-219}, doi = {10.1097/SPV.0000000000001090}, pmid = {34608030}, issn = {2154-4212}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Drug Resistance, Microbial/genetics ; Escherichia coli/genetics ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; *Urinary Tract Infections/drug therapy/microbiology ; }, abstract = {OBJECTIVE: The aims of this study were to describe the fecal relative abundance of potentially uropathogenic bacteria and to analyze antibiotic resistance genes before and after fecal microbiota transplantation in women with recurrent urinary tract infection (UTI).<br><br>METHODS: Shotgun sequencing was performed on fecal samples from 3 donors and 4 women with recurrent UTI who underwent transplantation. Recipient samples were sequenced at baseline and at 4 time points through 6 months postintervention. Relative fecal uropathogen abundance was analyzed by species and participant using descriptive statistics. Antibiotic resistance gene abundance was assigned, normalized, and compared between donors and recipients at baseline and postintervention using an abundance bar plot, nonmetric multidimensional scaling, and pairwise permutational multivariate analysis of variance.<br><br>RESULTS: The median (range) relative abundance of Escherichia coli in all fecal samples from women with recurrent UTI was 0% (0%-5.10%); Enterococcus faecalis, 0% (0%-0.20%); Enterococcus faecium, 0% (0%-1.90%); Klebsiella pneumoniae, 0% (0%-0.10%); and Pseudomonas aeruginosa, 0% (0%-0.10%). Gut microbes carried genes conferring resistance to antibiotics used for UTI. No significant difference was seen in antibiotic resistance gene carriage after transplantation compared with baseline (P=0.22, R2=0.08 at 3 months). Antibiotic gene composition and abundance were significantly associated with the individual from whom the sample came (P=0.004, R2=0.78 at 3 months).<br><br>CONCLUSIONS: Exploratory analysis of gut microbiomes in women with recurrent UTI identifies no or low relative putative uropathogen abundance for all species examined. Antibiotic resistance gene carriage persisted after fecal microbiota transplantation, although conclusions are limited by small sample size.}, }
@article {pmid34606847, year = {2022}, author = {Lima, SF and Gogokhia, L and Viladomiu, M and Chou, L and Putzel, G and Jin, WB and Pires, S and Guo, CJ and Gerardin, Y and Crawford, CV and Jacob, V and Scherl, E and Brown, SE and Hambor, J and Longman, RS}, title = {Transferable Immunoglobulin A-Coated Odoribacter splanchnicus in Responders to Fecal Microbiota Transplantation for Ulcerative Colitis Limits Colonic Inflammation.}, journal = {Gastroenterology}, volume = {162}, number = {1}, pages = {166-178}, pmid = {34606847}, issn = {1528-0012}, support = {R01 DK114252/DK/NIDDK NIH HHS/United States ; R01 DK120985/DK/NIDDK NIH HHS/United States ; R01 DK128257/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteroidetes/genetics/*immunology/metabolism ; Clinical Trials as Topic ; Colitis/immunology/metabolism/microbiology/*therapy ; Colitis, Ulcerative/diagnosis/immunology/metabolism/microbiology ; Colon/immunology/metabolism/*microbiology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Forkhead Transcription Factors/metabolism ; *Gastrointestinal Microbiome/genetics/immunology ; Germ-Free Life ; Humans ; Immunity, Mucosal ; Immunoglobulin A/genetics/*immunology/metabolism ; Intestinal Mucosa/immunology/metabolism/*microbiology ; Intraepithelial Lymphocytes/immunology/metabolism/microbiology ; Metagenome ; Metagenomics ; Mice, Inbred C57BL ; Mice, Knockout ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; T-Lymphocytes, Regulatory/immunology/metabolism/microbiology ; Treatment Outcome ; Mice ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is an emerging treatment modality for ulcerative colitis (UC). Several randomized controlled trials have shown efficacy for FMT in the treatment of UC, but a better understanding of the transferable microbiota and their immune impact is needed to develop more efficient microbiome-based therapies for UC.<br><br>METHODS: Metagenomic analysis and strain tracking was performed on 60 donor and recipient samples receiving FMT for active UC. Sorting and sequencing of immunoglobulin (Ig) A-coated microbiota (called IgA-seq) was used to define immune-reactive microbiota. Colonization of germ-free or genetically engineered mice with patient-derived strains was performed to determine the mechanism of microbial impact on intestinal immunity.<br><br>RESULTS: Metagenomic analysis defined a core set of donor-derived transferable bacterial strains in UC subjects achieving clinical response, which predicted response in an independent trial of FMT for UC. IgA-seq of FMT recipient samples and gnotobiotic mice colonized with donor microbiota identified Odoribacter splanchnicus as a transferable strain shaping mucosal immunity, which correlated with clinical response and the induction of mucosal regulatory T cells. Colonization of mice with O splanchnicus led to an increase in Foxp3[+]/ROR&#x3b3;t[+] regulatory T cells, induction of interleukin (IL) 10, and production of short chain fatty acids, all of which were required for O splanchnicus to limit colitis in mouse models.<br><br>CONCLUSIONS: This work provides the first evidence of transferable, donor-derived strains that correlate with clinical response to FMT in UC and reveals O splanchnicus as a key component promoting both metabolic and immune cell protection from colitis. These mechanistic features will help&#xa0;enable strategies to enhance the efficacy of&#xa0;microbial therapy for UC. Clinicaltrials.gov ID NCT02516384.}, }
@article {pmid34604008, year = {2021}, author = {Al-Ali, D and Ahmed, A and Shafiq, A and McVeigh, C and Chaari, A and Zakaria, D and Bendriss, G}, title = {Fecal microbiota transplants: A review of emerging clinical data on applications, efficacy, and risks (2015-2020).}, journal = {Qatar medical journal}, volume = {2021}, number = {1}, pages = {5}, pmid = {34604008}, issn = {0253-8253}, abstract = {As the importance of the gut microbiota in health and disease is a subject of growing interest, fecal microbiota transplantation (FMT) was suggested as an attractive therapeutic strategy to restore homeostasis of the gut microbiota, thereby treating diseases that were associated with alteration of the gut microbiota. FMT involves the administration of fresh, frozen, or dried fecal microorganisms from the gut of a healthy donor into the intestinal tract of a patient. This rediscovery of the potential benefits of an ancient practice was accompanied by a rapid progression of our understanding of the roles and mechanisms of gut microbes in the pathogenesis of disease. With a growing number of diseases being associated with dysbiosis or the alteration of gut microbiota, FMT was suggested as an attractive therapeutic strategy to "reset the gut" and initiate clinical resolutions or remissions. The number of FMT clinical trials is increasing worldwide, but no trials are registered in the Gulf region; this suggested the need for raising awareness of the latest studies on FMT. This review presented the emergent preclinical and clinical data to give an overview of the potential clinical applications, the benefits, and inconveniences that were worth considering for eventual future testing of fecal transplants in Qatar and the Middle East. This study highlighted the diversity of methods tested and commented on the variables that can affect the assessment of the effectiveness of FMT in specific diseases. The risks associated with FMT and the threat of antimicrobial resistance for this therapeutic approach were reviewed. From gastrointestinal diseases to neurodevelopmental disorders, understanding the roles of the gut microbiota in health and disease should be at the heart of developing novel, standardized, yet personalized, methods for this ancient therapeutic approach.}, }
@article {pmid34603515, year = {2021}, author = {Baruch, EN and Gaglani, T and Wargo, JA}, title = {Fecal microbiota transplantation as a mean of overcoming immunotherapy-resistant cancers - hype or hope?.}, journal = {Therapeutic advances in medical oncology}, volume = {13}, number = {}, pages = {17588359211045853}, pmid = {34603515}, issn = {1758-8340}, }
@article {pmid34602643, year = {2021}, author = {Costa, M and Di Pietro, R and Bessegatto, JA and Pereira, PFV and Stievani, FC and Gomes, RG and Lisbôa, JAN and Weese, JS}, title = {Evaluation of changes in microbiota after fecal microbiota transplantation in 6 diarrheic horses.}, journal = {The Canadian veterinary journal = La revue veterinaire canadienne}, volume = {62}, number = {10}, pages = {1123-1130}, pmid = {34602643}, issn = {0008-5286}, mesh = {Animals ; Bacteria ; Diarrhea/therapy/veterinary ; *Fecal Microbiota Transplantation/veterinary ; Feces ; Horses ; *Microbiota ; Treatment Outcome ; }, abstract = {The purpose of this study was to characterize the fecal microbiota of horses with acute and chronic diarrhea before and after fecal microbiota transplantation (FMT). Six client-owned horses with acute and chronic diarrhea received FMT from 2 healthy donor horses. Microbiota analysis using next-generation sequencing was performed on fecal samples collected before and 2 and 7 d after FMT. Signs of diarrhea improved in 4 horses, whereas the remaining 2 horses did not survive. There was a significant difference in the number of bacterial species between donors and recipients (P < 0.05). The Order Lactobacillales and the genera Lactobacillus, Intestinimonas, and Streptococcus were increased in the microbiota of diarrheic horses, and Saccharofermentans genus increased in healthy donors. The results suggest that FMT from the healthy donors was not effective over a 7-day period as it did not change the fecal microbiota of the diarrheic horses. Further research to improve the efficacy of FMT in horses is needed.}, }
@article {pmid34599164, year = {2021}, author = {Natarajan, A and Han, A and Zlitni, S and Brooks, EF and Vance, SE and Wolfe, M and Singh, U and Jagannathan, P and Pinsky, BA and Boehm, A and Bhatt, AS}, title = {Standardized preservation, extraction and quantification techniques for detection of fecal SARS-CoV-2 RNA.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {5753}, pmid = {34599164}, issn = {2041-1723}, support = {R01 AI148623/AI/NIAID NIH HHS/United States ; R01AI143757//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R01 AI143757/AI/NIAID NIH HHS/United States ; GRFP//National Science Foundation (NSF)/ ; R01AI148623//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; }, mesh = {COVID-19/diagnosis ; COVID-19 Nucleic Acid Testing/*standards ; Coronavirus Nucleocapsid Proteins/genetics ; Feces/*virology ; Humans ; Phosphoproteins/genetics ; Preservation, Biological/standards ; RNA, Viral/analysis/genetics ; Reagent Kits, Diagnostic ; Reference Standards ; SARS-CoV-2/genetics/*isolation &amp; purification ; Specimen Handling/standards ; Viral Load/standards ; }, abstract = {Patients with COVID-19 shed SARS-CoV-2 RNA in stool, sometimes well after their respiratory infection has cleared. This may be significant for patient health, epidemiology, and diagnosis. However, methods to preserve stool, and to extract and quantify viral RNA are not standardized. We test the performance of three preservative approaches at yielding detectable SARS-CoV-2 RNA: the OMNIgene-GUT kit, Zymo DNA/RNA shield kit, and the most commonly applied, storage without preservative. We test these in combination with three extraction kits: QIAamp Viral RNA Mini Kit, Zymo Quick-RNA Viral Kit, and MagMAX Viral/Pathogen Kit. We also test the utility of ddPCR and RT-qPCR for the reliable quantification of SARS-CoV-2 RNA from stool. We identify that the Zymo DNA/RNA preservative and the QiaAMP extraction kit yield more detectable RNA than the others, using both ddPCR and RT-qPCR. Taken together, we recommend a comprehensive methodology for preservation, extraction and detection of RNA from SARS-CoV-2 and other coronaviruses in stool.}, }
@article {pmid34598959, year = {2021}, author = {Kido, M and Tamura, R and Yasui, Y and Okajima, H}, title = {Novel application of infliximab for diversion colitis.}, journal = {BMJ case reports}, volume = {14}, number = {10}, pages = {}, pmid = {34598959}, issn = {1757-790X}, mesh = {Adult ; Colectomy ; *Colitis/chemically induced/drug therapy ; *Colitis, Ulcerative/drug therapy/surgery ; Humans ; Infliximab/therapeutic use ; Male ; Mesalamine/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {Diversion colitis (DC) that was refractory to standard treatments was successfully treated with infliximab. A 24-year-old man with a transverse colostomy suffered from severe DC. Topical steroids, 5-aminosalicylic acid (5-ASA) enemas and synbiotics were initially effective, and the colostomy was successfully closed with a covering ileostomy to minimise the risk of anastomotic leakage owing to the damaged colon. DC subsequently relapsed in the entire colon and was refractory to the previous protocol and autologous faecal transplantation. Intravenous methylprednisolone and oral 5-ASA were discontinued owing to possible adverse effects. Infliximab with intravenous prednisolone was introduced, and the protocol was so effective in suppressing the acute colitis that total colectomy was avoided. The stoma was subsequently closed, and the patient is currently symptom-free. Infliximab is used for ulcerative colitis but could also be effective against severe DC.}, }
@article {pmid34598315, year = {2022}, author = {Czarnecka, K and Czarnecka, P and Tronina, O and Bączkowska, T and Durlik, M}, title = {Multidirectional facets of obesity management in the metabolic syndrome population after liver transplantation.}, journal = {Immunity, inflammation and disease}, volume = {10}, number = {1}, pages = {3-21}, pmid = {34598315}, issn = {2050-4527}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Liver Transplantation ; *Metabolic Syndrome/therapy ; *Non-alcoholic Fatty Liver Disease/therapy ; *Obesity Management ; }, abstract = {The obesity pandemic has resulted in an increasing demand for liver transplantation and has significantly altered the profile of liver transplant candidates in addition to affecting posttransplantation outcomes. In this review, we discuss a broad range of clinical approaches that warrant attention to provide comprehensive and patient-centred medical care to liver transplant recipients, and to be prepared to confront the rapidly changing clinical challenges and ensuing dilemmas. Adipose tissue is a complex and metabolically active organ. Visceral fat deposition is a key predictor of overall obesity-related morbidity and mortality. Limited pharmacological options are available for the treatment of obesity in the liver transplant population. Bariatric surgery may be an alternative in eligible patients. The rapidly increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global concern; NAFLD affects both pre- and posttransplantation outcomes. Numerous studies have investigated pharmacological and nonpharmacological management of NAFLD and some of these have shown promising results. Liver transplant recipients are constantly exposed to numerous factors that result in intestinal microbiota alterations, which were linked to the development of obesity, diabetes type 2, metabolic syndrome (MS), NAFLD, and hepatocellular cancer. Microbiota modifications with probiotics and prebiotics bring gratifying results in the management of metabolic complications. Fecal microbiota transplantation (FMT) is successfully performed in many medical indications. However, the safety and efficacy profiles of FMT in immunocompromised patients remain unclear. Obesity together with immunosuppressive treatment, may affect the pharmacokinetic and/or pharmacodynamic properties of coadministered medications. Individualized immunosuppressive regimens are recommended following liver transplantation to address possible metabolic concerns. Effective and comprehensive management of metabolic complications is shown to yield multiple beneficial results in the liver transplant population and may bring gratifying results in improving long-term survival rates.}, }
@article {pmid34596608, year = {2021}, author = {Nicholson, MR and Kahn, SA}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis: Dispelling the "Yuck Factor".}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {73}, number = {6}, pages = {663-664}, doi = {10.1097/MPG.0000000000003315}, pmid = {34596608}, issn = {1536-4801}, mesh = {*Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid34596506, year = {2021}, author = {de Maria, YNLF and Aciole Barbosa, D and Menegidio, FB and Santos, KBNH and Humberto, AC and Alencar, VC and Silva, JFS and Costa de Oliveira, R and Batista, ML and Nunes, LR and Jabes, DL}, title = {Analysis of mouse faecal dysbiosis, during the development of cachexia, induced by transplantation with Lewis lung carcinoma cells.}, journal = {Microbiology (Reading, England)}, volume = {167}, number = {10}, pages = {}, doi = {10.1099/mic.0.001088}, pmid = {34596506}, issn = {1465-2080}, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification ; Cachexia/etiology/*microbiology ; Carcinoma, Lewis Lung/*pathology ; Cell Line, Tumor ; Disease Models, Animal ; Dysbiosis/etiology/*microbiology ; Feces/*microbiology ; Gastrointestinal Microbiome ; Mice ; Neoplasm Transplantation/*adverse effects ; Phylogeny ; }, abstract = {Cachexia (CC) is a complex wasting syndrome that significantly affects life quality and life expectancy among cancer patients. Original studies, in which CC was induced in mouse models through inoculation with BaF and C26 tumour cells, demonstrated that CC development correlates with bacterial gut dysbiosis in these animals. In both cases, a common microbial signature was observed, based on the expansion of Enterobacteriaceae in the gut of CC animals. However, these two types of tumours induce unique microbial profiles, suggesting that different CC induction mechanisms significantly impact the outcome of gut dysbiosis. The present study sought to expand the scope of such analyses by characterizing the CC-associated dysbiosis that develops when mice are inoculated with Lewis lung carcinoma (LLC) cells, which constitutes one of the most widely employed mechanisms for CC induction. Interestingly, Enterobacteriaceae expansion is also observed in LLC-induced CC. However, the dysbiosis identified herein displays a more complex pattern, involving representatives from seven different bacterial phyla, which were consistently identified across successive levels of taxonomic hierarchy. These results are supported by a predictive analysis of gene content, which identified a series of functional/structural changes that potentially occur in the gut bacterial population of these animals, providing a complementary and alternative approach to microbiome analyses based solely on taxonomic classification.}, }
@article {pmid34595189, year = {2021}, author = {Yan, Z and Deng, W and Wang, Y and Liu, Y and Sun, H and Xia, R and Zeng, W and Geng, J and Chen, G and He, X and Xu, J and Wu, CL and Miao, Y}, title = {Case Report: Malacoplakia Due to E. coli With Cryptococcus albidus Infection of a Transplanted Kidney in a Patient With Recurrent Urinary Tract Infection.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {721145}, pmid = {34595189}, issn = {2296-858X}, abstract = {Background: Colonization of Cryptococcus rarely occurs in a graft. This study reports a case of malacoplakia and cryptococcoma caused by E. coli and Cryptococcus albidus in a transplanted kidney, with detailed pathology and metagenome sequencing analysis. Case Presentation: We presented a case of cryptococcoma and malacoplakia in the genitourinary system including the transplant kidney, bladder, prostate, and seminal vesicles caused by Cryptococcus albidus and Escherichia coli in a renal-transplant recipient. Metagenome sequencing was conducted on a series of samples obtained from the patient at three different time points, which we termed Phase I (at the diagnosis of cryptococcoma), Phase II (during perioperative period of graftectomy, 3 months after the diagnosis), and Phase III (2 months after graftectomy). Sequencing study in the Phase I detected two and four sequences of C. albidus respectively in cerebrospinal fluid (CSF) and feces, with resistant Escherichia coli 09-02E presented in urine and renal mass. A 3-month antibiotic treatment yielded a smaller bladder lesion but an enlarged allograft lesion, leading to a nephrectomy. In the Phase II, two sequences of C. albidus were detected in CSF, while the E. coli 09-02E continued as before. In the Phase III, the lesions were generally reduced, with one C. albidus sequence in feces only. Conclusions: The existence and clearance of Cryptococcus sequences in CSF without central nervous system symptoms may be related to the distribution of infection foci in vivo, the microbial load, and the body's immunity. Overall, this study highlights the need for enhanced vigilance against uncommon types of Cryptococcus infections in immunocompromised populations and increased concern about the potential correlation between E. coli and Cryptococcus infections.}, }
@article {pmid34593556, year = {2021}, author = {Chadchan, SB and Popli, P and Ambati, CR and Tycksen, E and Han, SJ and Bulun, SE and Putluri, N and Biest, SW and Kommagani, R}, title = {Gut microbiota-derived short-chain fatty acids protect against the progression of endometriosis.}, journal = {Life science alliance}, volume = {4}, number = {12}, pages = {}, pmid = {34593556}, issn = {2575-1077}, support = {R01 HD098059/HD/NICHD NIH HHS/United States ; P30 CA091842/CA/NCI NIH HHS/United States ; R00 HD080742/HD/NICHD NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; R01 HD065435/HD/NICHD NIH HHS/United States ; R01 HD102680/HD/NICHD NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*metabolism ; Butyrates/*administration &amp; dosage/*metabolism ; Cell Line, Transformed ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Disease Models, Animal ; Endometriosis/drug therapy/*metabolism/*microbiology/pathology ; Epithelial Cells/drug effects/metabolism ; Feces/chemistry/microbiology ; Female ; *Gastrointestinal Microbiome ; Heterografts ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Nude ; Protective Agents/*administration &amp; dosage/*metabolism ; Shelterin Complex/metabolism ; Signal Transduction/*drug effects/genetics ; Stromal Cells/drug effects/metabolism ; Telomere-Binding Proteins/metabolism ; Transfection ; }, abstract = {Worldwide, ∼196 million are afflicted with endometriosis, a painful disease in which endometrial tissue implants and proliferates on abdominal peritoneal surfaces. Theories on the origin of endometriosis remained inconclusive. Whereas up to 90% of women experience retrograde menstruation, only 10% develop endometriosis, suggesting that factors that alter peritoneal environment might contribute to endometriosis. Herein, we report that whereas some gut bacteria promote endometriosis, others protect against endometriosis by fermenting fiber to produce short-chain fatty acids. Specifically, we found that altered gut microbiota drives endometriotic lesion growth and feces from mice with endometriosis contained less of short-chain fatty acid and n-butyrate than feces from mice without endometriosis. Treatment with n-butyrate reduced growth of both mouse endometriotic lesions and human endometriotic lesions in a pre-clinical mouse model. Mechanistic studies revealed that n-butyrate inhibited human endometriotic cell survival and lesion growth through G-protein-coupled receptors, histone deacetylases, and a GTPase activating protein, RAP1GAP. Our findings will enable future studies aimed at developing diagnostic tests, gut bacteria metabolites and treatment strategies, dietary supplements, n-butyrate analogs, or probiotics for endometriosis.}, }
@article {pmid34590904, year = {2021}, author = {Vuyyuru, SK and Kedia, S and Kalaivani, M and Sahu, P and Kante, B and Kumar, P and Ranjan, MK and Makharia, G and Ananthakrishnan, A and Ahuja, V}, title = {Efficacy and safety of fecal transplantation versus targeted therapies in ulcerative colitis: network meta-analysis.}, journal = {Future microbiology}, volume = {16}, number = {}, pages = {1215-1227}, doi = {10.2217/fmb-2020-0242}, pmid = {34590904}, issn = {1746-0921}, mesh = {Adalimumab/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; *Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation ; Humans ; Network Meta-Analysis ; Randomized Controlled Trials as Topic ; }, abstract = {Aim: We conducted this network meta-analysis to compare the efficacy and safety of targeted pharmacotherapies and fecal microbial transplantation (FMT). Patients &amp; methods: Nineteen studies were included and there was only one head-to-head randomized controlled trial (adalimumab vs vedolizumab). Results: All interventions, including FMT, were superior to a placebo in inducing clinical remission (except adalimumab - odds ratio 1.66; 95% CI: 0.97-2.85), clinical response and endoscopic remission. FMT was comparable with other agents in achieving all efficacy outcomes. Infliximab was ranked highest in inducing clinical remission (surface under the cumulative ranking, 0.8). There was no difference in safety outcomes between FMT and other targeted therapies. Conclusion: FMT is as efficacious and as safe as other targeted therapies in inducing clinical remission, clinical response and endoscopic remission. Further studies to assess the long-term benefits are needed in order to reach a definitive conclusion.}, }
@article {pmid34589510, year = {2021}, author = {Rong, Z and Huang, Y and Cai, H and Chen, M and Wang, H and Liu, G and Zhang, Z and Wu, J}, title = {Gut Microbiota Disorders Promote Inflammation and Aggravate Spinal Cord Injury Through the TLR4/MyD88 Signaling Pathway.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {702659}, pmid = {34589510}, issn = {2296-861X}, abstract = {Background: In spinal cord injury (SCI), systemic inflammation and the death of nerve cells in the spinal cord are life threatening. The connection between gut microbiota and signaling pathways has been a hot research topic in recent years. The Toll-like receptor 4/Myeloid differentiation factor 88 (TLR4/MyD88) signaling pathway is closely related to the inflammatory response. This study explored whether the gut microbiota imbalance could affect the TLR4/MyD88 signaling pathway to regulate SCI to provide a new basis for SCI research and treatment. Methods: An SCI model was constructed to study the influence on the injury of gut microbiota. 16S amplicon sequencing was used to identify the diversity and abundance of gut microbes. Fecal microbiota transplantation was performed in mice with SCI. ELISA was used to detect the serum levels of pro-inflammatory and anti-inflammatory factors in mice. Hematoxylin and eosin staining was used to observe SCI in mice. Immunofluorescence was used to detect the rates of loss glial fibrillary acidic protein (GFAP), neuronal nuclear protein (NeuN), and ionized calcium-binding adapter molecule 1 (IBA1) in the spinal cord as indicators of apoptosis. The expression of the TLR4/MyD88 signaling pathway was detected by qRT-PCR and western blotting. Results: Significant differences were observed in the gut microbiota of SCI mice and normal mice. The gut microbiota of SCI mice was imbalanced. The levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in SCI mice were increased, as was the level of the toxic induced nitric oxide synthase. The levels of anti-inflammatory factors IL-4, transforming growth factor-β, and IL-10 were decreased, as was the level of arginase-1. The apoptosis rates of GFAP, NeuN, and IBA1 were increased. The TLR4/MyD88 signaling pathway was activated. In the SCI group, inflammation increased after fecal transplantation, apoptosis of GFAP, NeuN, and IBA1 increased, and SCI was more serious. Conclusion: The TLR4/MyD88 signaling pathway promotes the death of nerve cells by inducing inflammation. Gut microbiota dysregulation can lead to aggravated SCI by activating the TLR4/MyD88 signaling pathway.}, }
@article {pmid34589427, year = {2021}, author = {Li, B and Gong, T and Hao, Y and Zhou, X and Cheng, L}, title = {Mining the Gut Microbiota for Microbial-Based Therapeutic Strategies in Cancer Immunotherapy.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {721249}, pmid = {34589427}, issn = {2234-943X}, abstract = {The past two decades witnessed a revolution in our understanding of host-microbiota interactions that led to the concept of the super-organism consisting of a eukaryotic part and a prokaryotic part. Owing to the critical role of gut microbiota in modulating the host immune system, it is not beyond all expectations that more and more evidence indicated that the shift of gut microbiota influenced responses to numerous forms of cancer immunotherapy. Therapy targeting gut microbiota is becoming a promising strategy to improve cancer immunotherapy. In this review, we discuss the role of the gut microbiota in response to cancer immunotherapy, the mechanisms that the gut microbiota influences cancer immunotherapy, and therapeutic strategies targeting gut microbiota to improve cancer immunotherapy.}, }
@article {pmid34588747, year = {2021}, author = {Milosevic, I and Russo, E and Vujovic, A and Barac, A and Stevanovic, O and Gitto, S and Amedei, A}, title = {Microbiota and viral hepatitis: State of the art of a complex matter.}, journal = {World journal of gastroenterology}, volume = {27}, number = {33}, pages = {5488-5501}, pmid = {34588747}, issn = {2219-2840}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Hepatitis, Viral, Human ; Humans ; *Microbiota ; }, abstract = {Changes in gut microbiota influence both the gut and liver, which are strictly connected by the so-called "gut-liver axis". The gut microbiota acts as a major determinant of this relationship in the onset and clinical course of liver diseases. According to the results of several studies, gut dysbiosis is linked to viral hepatitis, mainly hepatitis C virus and hepatitis B virus infection. Gut bacteria-derived metabolites and cellular components are key molecules that affect liver function and modulate the pathology of viral hepatitis. Recent studies showed that the gut microbiota produces various molecules, such as peptidoglycans, lipopolysaccharides, DNA, lipoteichoic acid, indole-derivatives, bile acids, and trimethylamine, which are translocated to the liver and interact with liver immune cells causing pathological effects. Therefore, the existence of crosstalk between the gut microbiota and the liver and its implications on host health and pathologic status are essential factors impacting the etiology and therapeutic approach. Concrete mechanisms behind the pathogenic role of gut-derived components on the pathogenesis of viral hepatitis remain unclear and not understood. In this review, we discuss the current findings of research on the bidirectional relationship of the components of gut microbiota and the progression of liver diseases and viral hepatitis and vice versa. Moreover, this paper highlights the current therapeutic and preventive strategies, such as fecal transplantation, used to restore the gut microbiota composition and so improve host health.}, }
@article {pmid34588655, year = {2021}, author = {Hofer, U}, title = {Faecal phage transplant to the rescue?.}, journal = {Nature reviews. Microbiology}, volume = {19}, number = {12}, pages = {744}, pmid = {34588655}, issn = {1740-1534}, mesh = {*Bacteriophages/genetics ; Fecal Microbiota Transplantation ; Feces ; }, }
@article {pmid34588617, year = {2022}, author = {Xie, X and Liu, J and Chen, X and Zhang, S and Tang, R and Wu, X and Zhang, W and Cao, Y}, title = {Gut microbiota involved in leptospiral infections.}, journal = {The ISME journal}, volume = {16}, number = {3}, pages = {764-773}, pmid = {34588617}, issn = {1751-7370}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Leptospirosis/microbiology ; Mice ; Mice, Inbred C57BL ; }, abstract = {Leptospirosis is a re-emerging zoonotic disease worldwide. Intestinal bleeding is a common but neglected symptom in severe leptospirosis. The regulatory mechanism of the gut microbiota on leptospirosis is still unclear. In this study, we found that Leptospira interrogans infection changed the composition of the gut microbiota in mice. Weight loss and an increased leptospiral load in organs were observed in the gut microbiota-depleted mice compared with those in the control mice. Moreover, fecal microbiota transplantation (FMT) to the microbiota-depleted mice reversed these effects. The phagocytosis response and inflammatory response in bone marrow-derived macrophages and thioglycolate-induced peritoneal macrophages were diminished in the microbiota-depleted mice after infection. However, the phagocytosis response and inflammatory response in resident peritoneal macrophage were not affected in the microbiota-depleted mice after infection. The diminished macrophage disappearance reaction (bacterial entry into the peritoneum acutely induced macrophage adherence to form local clots and out of the fluid phase) led to an increased leptospiral load in the peritoneal cavity in the microbiota-depleted mice. In addition, the impaired capacity of macrophages to clear leptospires increased leptospiral dissemination in Leptospira-infected microbiota-depleted mice. Our study identified the microbiota as an endogenous defense against L. interrogans infection. Modulating the structure and function of the gut microbiota may provide new individualized preventative strategies for the control of leptospirosis and related spirochetal infections.}, }
@article {pmid34587331, year = {2021}, author = {Biliński, J and Jasiński, M and Tomaszewska, A and Lis, K and Kacprzyk, P and Chmielewska, L and Karakulska-Prystupiuk, E and Mullish, BH and Basak, GW}, title = {Fecal microbiota transplantation with ruxolitinib as a treatment modality for steroid-refractory/dependent acute, gastrointestinal graft-versus-host disease: A case series.}, journal = {American journal of hematology}, volume = {96}, number = {12}, pages = {E461-E463}, doi = {10.1002/ajh.26365}, pmid = {34587331}, issn = {1096-8652}, support = {CL-2019-21-002/DH_/Department of Health/United Kingdom ; }, mesh = {Acute Disease ; Aged ; *Fecal Microbiota Transplantation ; Female ; Graft vs Host Disease/*therapy ; Humans ; Janus Kinases/antagonists &amp; inhibitors ; Male ; Middle Aged ; Nitriles/*therapeutic use ; Protein Kinase Inhibitors/*therapeutic use ; Pyrazoles/*therapeutic use ; Pyrimidines/*therapeutic use ; Steroids/therapeutic use ; }, }
@article {pmid34586890, year = {2021}, author = {Simsek, C and Bloemen, M and Jansen, D and Beller, L and Descheemaeker, P and Reynders, M and Van Ranst, M and Matthijnssens, J}, title = {High Prevalence of Coinfecting Enteropathogens in Suspected Rotavirus Vaccine Breakthrough Cases.}, journal = {Journal of clinical microbiology}, volume = {59}, number = {12}, pages = {e0123621}, pmid = {34586890}, issn = {1098-660X}, support = {721367/MCCC_/Marie Curie/United Kingdom ; }, mesh = {Child ; Feces ; Humans ; Prevalence ; Real-Time Polymerase Chain Reaction ; *Rotavirus Vaccines ; }, abstract = {Despite the global use of rotavirus vaccines, vaccine breakthrough cases remain a pediatric health problem. In this study, we investigated suspected rotavirus vaccine breakthrough cases using next-generation sequencing (NGS)-based viral metagenomics (n = 102) and a panel of semiquantitative reverse transcription-PCR (RT-qPCR) (n = 92) targeting known enteric pathogens. Overall, we identified coinfections in 80% of the cases. Enteropathogens such as adenovirus (32%), enterovirus (15%), diarrheagenic Escherichia coli (1 to 14%), astrovirus (10%), Blastocystis spp. (10%), parechovirus (9%), norovirus (9%), Clostridioides (formerly Clostridium) difficile (9%), Dientamoeba fragilis (9%), sapovirus (8%), Campylobacter jejuni (4%), and Giardia lamblia (4%) were detected. Except for a few reassortant rotavirus strains, unusual genotypes or genotype combinations were not present. However, in addition to well-known enteric viruses, divergent variants of enteroviruses and nonclassic astroviruses were identified using NGS. We estimated that in 31.5% of the patients, rotavirus was likely not the cause of gastroenteritis, and in 14.1% of the patients, it contributed together with another pathogen(s) to disease. The remaining 54.4% of the patients likely had a true vaccine breakthrough infection. The high prevalence of alternative enteropathogens in the suspected rotavirus vaccine breakthrough cases suggests that gastroenteritis is often the result of a coinfection and that rotavirus vaccine effectiveness might be underestimated in clinical and epidemiological studies.}, }
@article {pmid34586012, year = {2021}, author = {Pothuraju, R and Chaudhary, S and Rachagani, S and Kaur, S and Roy, HK and Bouvet, M and Batra, SK}, title = {Mucins, gut microbiota, and postbiotics role in colorectal cancer.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1974795}, pmid = {34586012}, issn = {1949-0984}, support = {R01 CA247471/CA/NCI NIH HHS/United States ; R01 CA254036/CA/NCI NIH HHS/United States ; I01 BX004494/BX/BLRD VA/United States ; R43 CA235984/CA/NCI NIH HHS/United States ; P01 CA217798/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Colorectal Neoplasms/*drug therapy/genetics/metabolism/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/metabolism/microbiology ; Mucins/genetics/*metabolism ; Prebiotics/analysis ; Probiotics/*administration &amp; dosage ; }, abstract = {An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, which results in inflammatory diseases and colorectal cancer. The colon epithelium protects itself from a harsh environment and various pathogenic organisms by forming a double mucus layer, primarily comprising mucins. Recent studies are focusing on how dietary patterns alter the gut microbiota composition, which in turn regulates mucin expression and maintains the intestinal layers. In addition, modulation of gut microbiota by microbiotic therapy (involving fecal microbiota transplantation) has emerged as a significant factor in the pathologies associated with dysbiosis. Therefore, proper communication between host and gut microbiota via different dietary patterns (prebiotics and probiotics) is needed to maintain mucus composition, mucin synthesis, and regulation. Here, we review how the interactions between diet and gut microbiota and bacterial metabolites (postbiotics) regulate mucus layer functionalities and mucin expression in human health and disease.}, }
@article {pmid34586011, year = {2021}, author = {Secombe, KR and Al-Qadami, GH and Subramaniam, CB and Bowen, JM and Scott, J and Van Sebille, YZA and Snelson, M and Cowan, C and Clarke, G and Gheorghe, CE and Cryan, JF and Wardill, HR}, title = {Guidelines for reporting on animal fecal transplantation (GRAFT) studies: recommendations from a systematic review of murine transplantation protocols.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1979878}, pmid = {34586011}, issn = {1949-0984}, mesh = {Animals ; Clostridioides difficile/genetics/physiology ; Clostridium Infections/microbiology/*therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation/methods/*standards ; Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {Fecal microbiota transplant (FMT) is a powerful tool used to connect changes in gut microbial composition with a variety of disease states and pathologies. While FMT enables potential causal relationships to be identified, the experimental details reported in preclinical FMT protocols are highly inconsistent and/or incomplete. This limitation reflects a current lack of authoritative guidance on reporting standards that would facilitate replication efforts and ultimately reproducible science. We therefore systematically reviewed all FMT protocols used in mouse models with the goal of formulating recommendations on the reporting of preclinical FMT protocols. Search strategies were applied across three databases (PubMed, EMBASE, and Ovid Medline) until June 30, 2020. Data related to donor attributes, stool collection, processing/storage, recipient preparation, administration, and quality control were extracted. A total of 1753 papers were identified, with 241 identified for data extraction and analysis. Of the papers included, 92.5% reported a positive outcome with FMT intervention. However, the vast majority of studies failed to address core methodological aspects including the use of anaerobic conditions (91.7% of papers lacked information), storage (49.4%), homogenization (33.6%), concentration (31.5%), volume (19.9%) and administration route (5.3%). To address these reporting limitations, we developed theGuidelines for Reporting Animal Fecal Transplant (GRAFT) that guide reporting standards for preclinical FMT. The GRAFT recommendations will enable robust reporting of preclinical FMT design, and facilitate high-quality peer review, improving the rigor and translation of knowledge gained through preclinical FMT studies.}, }
@article {pmid34585964, year = {2021}, author = {Tomkovich, S and Taylor, A and King, J and Colovas, J and Bishop, L and McBride, K and Royzenblat, S and Lesniak, NA and Bergin, IL and Schloss, PD}, title = {An Osmotic Laxative Renders Mice Susceptible to Prolonged Clostridioides difficile Colonization and Hinders Clearance.}, journal = {mSphere}, volume = {6}, number = {5}, pages = {e0062921}, pmid = {34585964}, issn = {2379-5042}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Clindamycin/therapeutic use ; Clostridioides difficile/*drug effects/*physiology ; Clostridium Infections/*drug therapy/microbiology/prevention &amp; control ; Disease Susceptibility ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Laxatives/*therapeutic use ; Mice ; Mice, Inbred C57BL ; Polyethylene Glycols/therapeutic use ; RNA, Ribosomal, 16S/analysis ; }, abstract = {Antibiotics are a major risk factor for Clostridioides difficile infections (CDIs) because of their impact on the microbiota. However, nonantibiotic medications such as the ubiquitous osmotic laxative polyethylene glycol 3350 (PEG 3350) also alter the microbiota. Clinicians also hypothesize that PEG helps clear C. difficile. But whether PEG impacts CDI susceptibility and clearance is unclear. To examine how PEG impacts susceptibility, we treated C57BL/6 mice with 5-day and 1-day doses of 15% PEG in the drinking water and then challenged the mice with C. difficile 630. We used clindamycin-treated mice as a control because they consistently clear C. difficile within 10 days postchallenge. PEG treatment alone was sufficient to render mice susceptible, and 5-day PEG-treated mice remained colonized for up to 30 days postchallenge. In contrast, 1-day PEG-treated mice were transiently colonized, clearing C. difficile within 7 days postchallenge. To examine how PEG treatment impacts clearance, we administered a 1-day PEG treatment to clindamycin-treated, C. difficile-challenged mice. Administering PEG to mice after C. difficile challenge prolonged colonization up to 30 days postchallenge. When we trained a random forest model with community data from 5 days postchallenge, we were able to predict which mice would exhibit prolonged colonization (area under the receiver operating characteristic curve [AUROC] = 0.90). Examining the dynamics of these bacterial populations during the postchallenge period revealed patterns in the relative abundances of Bacteroides, Enterobacteriaceae, Porphyromonadaceae, Lachnospiraceae, and Akkermansia that were associated with prolonged C. difficile colonization in PEG-treated mice. Thus, the osmotic laxative PEG rendered mice susceptible to C. difficile colonization and hindered clearance. IMPORTANCE Diarrheal samples from patients taking laxatives are typically rejected for Clostridioides difficile testing. However, there are similarities between the bacterial communities from people with diarrhea and those with C. difficile infections (CDIs), including lower diversity than the communities from healthy patients. This observation led us to hypothesize that diarrhea may be an indicator of C. difficile susceptibility. We explored how osmotic laxatives disrupt the microbiota's colonization resistance to C. difficile by administering a laxative to mice either before or after C. difficile challenge. Our findings suggest that osmotic laxatives disrupt colonization resistance to C. difficile and prevent clearance among mice already colonized with C. difficile. Considering that most hospitals recommend not performing C. difficile testing on patients taking laxatives, and laxatives are prescribed prior to administering fecal microbiota transplants via colonoscopy to patients with recurrent CDIs, further studies are needed to evaluate if laxatives impact microbiota colonization resistance in humans.}, }
@article {pmid34585961, year = {2021}, author = {Zhang, Z and Xu, D and Fang, J and Wang, D and Zeng, J and Liu, X and Hong, S and Xue, Y and Zhang, X and Zhao, X}, title = {In Situ Live Imaging of Gut Microbiota.}, journal = {mSphere}, volume = {6}, number = {5}, pages = {e0054521}, pmid = {34585961}, issn = {2379-5042}, mesh = {Animals ; Cricetinae ; Female ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Male ; Mice ; Mice, Inbred C57BL ; *Positron Emission Tomography Computed Tomography ; Sorbitol/administration &amp; dosage/analogs &amp; derivatives ; Spatio-Temporal Analysis ; }, abstract = {Most studies of gut microbiota have focused on relationships between a specific disease and the presence/abundance of one or a few bacterial species/genera. Whether the spatial and temporal distribution of gut microbiota, as a whole, affects or correlates with health is unknown, largely due to the absence of tools for dynamically monitoring the overall gut microbiota landscape inside living subjects. Here, we describe a novel, noninvasive, live imaging method for gut microbiota using 2-deoxy-2-[[18]F]fluoro-d-sorbitol ([18]F-FDS), a compound that specifically labeled gut bacteria in mice and hamsters following oral administration. Positron emission tomography-computed tomography (PET-CT) scanning showed that the radiolabel signal was concentrated in the gut (especially the large intestine), was absent when mice gut microbiota was depleted by antibiotic treatment, and was restored after transplanting antibiotic-treated mice with a fecal or probiotic bacterial mixture. Thus, [18]F-FDS images microbiota, not gut tissue. The tissue distribution of [18]F-FDS was the highest in the gut (∼3-fold higher than average), in contrast to 2-deoxy-2-[[18]F]fluoro-d-glucose, which concentrated in brain and many other organs. 2-[[18]F]fluoro-aminobenzoic acid, another bacterium-specific radioactive tracer, was unsuited for gut microbiota imaging due to unexpected stomach retention following oral administration. When similar gut microbiota imaging was done with hamsters, the spatial resolution increased significantly over that with mice, suggesting that even higher spatial resolution can be achieved with humans or large animals. Thus, our work establishes a new tool for noninvasive, live imaging of gut microbiota; the new tool may enable exploration of relationships between gut microbiota landscape and diseases in clinical settings. IMPORTANCE Gut microbiota dysbiosis correlates with many diseases, but such correlations derive mostly from relationships between one or a few bacteria and a particular disease. Since microbiota resemble complex forest ecosystems more closely than individual patches of trees, the overall landscape (spatial and temporal distribution) of gut bacteria may also affect/reflect disease development. Such a possibility has not been explored due to a lack of tools for directly visualizing natural landscape patterns of gut microbiota. The present work identified 2-deoxy-2-[[18]F]fluoro-d-sorbitol as a gut microbiota-specific radioactive tracer and developed a novel PET-CT scan-based imaging method that enables noninvasive, real-time imaging of the overall gut bacterial landscape. The method showed increased spatial resolution when hamsters replaced mice, suggesting that even higher spatial resolution could be achieved with larger animals such as humans. This novel technology establishes the feasibility of investigating spatial-temporal distribution dynamics of gut microbiota with many human diseases.}, }
@article {pmid34584982, year = {2021}, author = {Bryant, RV and Day, AS and McGrath, KC and Telfer, K and Yao, CK and Costello, SP}, title = {Fecal microbiota transplantation augmented by a sulfide-reducing diet for refractory ulcerative colitis: A case report with functional metagenomic analysis.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {5}, number = {9}, pages = {1099-1102}, pmid = {34584982}, issn = {2397-9070}, abstract = {Fecal microbiota transplantation (FMT) is effective for induction of remission in ulcerative colitis (UC). Diet has potential to augment the efficacy and durability of FMT by encouraging engraftment of transplanted microorganisms. A trial of FMT combined with a defined diet was undertaken as salvage therapy for a 71-year-old woman with active steroid-refractory extensive UC. A multidimensional sulfide-reducing diet (4-SURE diet) was commenced followed by single-donor FMT administered by colonoscopy and then enemas over 7 days. Dietary adherence, clinical evaluation, and stool samples for metagenomic profiling were undertaken at weeks 0, 4, 8, and 24. Colonoscopy was performed 8 weeks post-FMT. Shotgun metagenomic profiling of the donor fecal suspension was also performed. A rapid clinical response to FMT and 4-SURE diet was observed with normalization of stool frequency (≤2 motions/day) and resolution of rectal bleeding within 2 weeks. Dietary adherence was excellent. Colonoscopy at week 8 revealed no evidence of active colitis (Mayo endoscopic sub-score 0) with histology showing no evidence of acute or chronic lamina propria inflammatory cell infiltrate. Sustained clinical and endoscopic remission out to 24 weeks was observed. Metagenomic sequencing confirmed sustained engraftment of beneficial donor microbiota with increased alpha-diversity and capacity for short-chain fatty acid production, including Faecalibacterium prauznitzii and Eubacterium hallii. This case report supports the rationale of prescribed diet therapy to support engraftment of donor microbiota following FMT for UC. Further large trials with a diet-arm control group are needed to evaluate FMT augmented by a defined diet in UC.}, }
@article {pmid34584964, year = {2021}, author = {Wei, L and Singh, R and Ro, S and Ghoshal, UC}, title = {Gut microbiota dysbiosis in functional gastrointestinal disorders: Underpinning the symptoms and pathophysiology.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {5}, number = {9}, pages = {976-987}, pmid = {34584964}, issn = {2397-9070}, abstract = {Functional gastrointestinal disorders (FGIDs), currently known as disorders of gut-brain interaction, are emerging microbiota-gut-brain abnormalities that are prevalent worldwide. The pathogenesis of FGIDs is heterogeneous and is intertwined with gut microbiota and its derived molecule-modulated mechanisms, including gut dysmotility, visceral hypersensitivity, gut immune abnormalities, abnormal secretion, and impaired barrier function. There has been phenomenal progress in understanding the role of gut microbiota in FGIDs by underpinning the species alternations between healthy and pathological conditions such as FGIDs. However, the precise gut microbiota-directed cellular and molecular pathogeneses of FGIDs are yet enigmatic. Determining the mechanistic link between the gut microbiota and gastrointestinal (GI) diseases has been difficult due to (i) the lack of robust animal models imitating the various aspects of human FGID pathophysiology; (ii) the absence of longitudinal human and/or animal studies to unveil the interaction of the gut microbiota with FGID-relevant pathogenesis; (iii) uncertainty about connections between human and animal studies; and (iv) insufficient data supporting a holistic view of disease-specific pathophysiological changes in FGID patients. These unidentified gaps open possibilities to explore pathological mechanisms directed through gut microbiota dysbiosis in FGIDs. The current treatment options for dysbiotic gut microbiota are limited; dietary interventions, antibiotics, probiotics, and fecal microbiota transplantation are the front-line clinical options. Here, we review the contribution of gut microbiota and its derived molecules in gut homeostasis and explore the possible pathophysiological mechanisms involved in FGIDs leading to potential therapeutics options.}, }
@article {pmid34580907, year = {2021}, author = {Huang, HL and Xu, HM and Liu, YD and Shou, DW and Nie, YQ and Chen, HT and Zhou, YJ}, title = {Fecal microbiota transplantation as a novel approach for the treatment of atopic dermatitis.}, journal = {The Journal of dermatology}, volume = {48}, number = {12}, pages = {e574-e576}, doi = {10.1111/1346-8138.16169}, pmid = {34580907}, issn = {1346-8138}, mesh = {*Dermatitis, Atopic/therapy ; *Eczema ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid34580480, year = {2021}, author = {Wolter, M and Grant, ET and Boudaud, M and Steimle, A and Pereira, GV and Martens, EC and Desai, MS}, title = {Leveraging diet to engineer the gut microbiome.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {18}, number = {12}, pages = {885-902}, pmid = {34580480}, issn = {1759-5053}, mesh = {Autoimmune Diseases/immunology/*microbiology/physiopathology/*therapy ; Combined Modality Therapy ; Diet/*methods ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology/*physiology ; Humans ; Prebiotics ; Primary Prevention/methods ; Probiotics/therapeutic use ; }, abstract = {Autoimmune diseases, including inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, have distinct clinical presentations but share underlying patterns of gut microbiome perturbation and intestinal barrier dysfunction. Their potentially common microbial drivers advocate for treatment strategies aimed at restoring appropriate microbiome function, but individual variation in host factors makes a uniform approach unlikely. In this Perspective, we consolidate knowledge on diet-microbiome interactions in local inflammation, gut microbiota imbalance and host immune dysregulation. By understanding and incorporating the effects of individual dietary components on microbial metabolic output and host physiology, we examine the potential for diet-based therapies for autoimmune disease prevention and treatment. We also discuss tools targeting the gut microbiome, such as faecal microbiota transplantation, probiotics and orthogonal niche engineering, which could be optimized using custom dietary interventions. These approaches highlight paths towards leveraging diet for precise engineering of the gut microbiome at a time of increasing autoimmune disease.}, }
@article {pmid34580445, year = {2021}, author = {Aggarwala, V and Mogno, I and Li, Z and Yang, C and Britton, GJ and Chen-Liaw, A and Mitcham, J and Bongers, G and Gevers, D and Clemente, JC and Colombel, JF and Grinspan, A and Faith, J}, title = {Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes.}, journal = {Nature microbiology}, volume = {6}, number = {10}, pages = {1309-1318}, pmid = {34580445}, issn = {2058-5276}, support = {R01 DK123749/DK/NIDDK NIH HHS/United States ; U24 CA224319/CA/NCI NIH HHS/United States ; U01 DK124165/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/classification/genetics/*isolation &amp; purification ; Benchmarking ; Clostridioides difficile/physiology ; Clostridium Infections/microbiology/therapy ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Metagenome/genetics ; Recurrence ; Tissue Donors ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has been successfully applied to treat recurrent Clostridium difficile infection in humans, but a precise method to measure which bacterial strains stably engraft in recipients and evaluate their association with clinical outcomes is lacking. We assembled a collection of >1,000 different bacterial strains that were cultured from the fecal samples of 22 FMT donors and recipients. Using our strain collection combined with metagenomic sequencing data from the same samples, we developed a statistical approach named Strainer for the detection and tracking of bacterial strains from metagenomic sequencing data. We applied Strainer to evaluate a cohort of 13 FMT longitudinal clinical interventions and detected stable engraftment of 71% of donor microbiota strains in recipients up to 5 years post-FMT. We found that 80% of recipient gut bacterial strains pre-FMT were eliminated by FMT and that post-FMT the strains present persisted up to 5 years later, together with environmentally acquired strains. Quantification of donor bacterial strain engraftment in recipients independently explained (precision 100%, recall 95%) the clinical outcomes (relapse or success) after initial and repeat FMT. We report a compendium of bacterial species and strains that consistently engraft in recipients over time that could be used in defined live biotherapeutic products as an alternative to FMT. Our analytical framework and Strainer can be applied to systematically evaluate either FMT or defined live bacterial therapeutic studies by quantification of strain engraftment in recipients.}, }
@article {pmid34579027, year = {2021}, author = {Yang, M and Gu, Y and Li, L and Liu, T and Song, X and Sun, Y and Cao, X and Wang, B and Jiang, K and Cao, H}, title = {Bile Acid-Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside.}, journal = {Nutrients}, volume = {13}, number = {9}, pages = {}, pmid = {34579027}, issn = {2072-6643}, support = {82070545 and 81970477//National Natural Science Foundation of China/ ; 20YFZCSY00020//Key Project of Science and Technology Pillar Program of Tianjin/ ; }, mesh = {Animals ; Bile Acids and Salts/metabolism/*physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammatory Bowel Diseases/*etiology ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial composition marked by the depletion of phylum Firmicutes (including bacteria involved in bile acid metabolism) and the enrichment of phylum Proteobacteria. Dysbiosis leads to blocked bile acid transformation. Thus, the concentration of primary and conjugated bile acids is elevated at the expense of secondary bile acids in IBD. In turn, bile acids could modulate the microbial community. Gut dysbiosis and disturbed bile acids impair the gut barrier and immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal microbiota transplantation and ursodeoxycholic acid, may alleviate IBD by restoring gut microbiota and bile acids. Thus, the bile acid-gut microbiota axis is closely connected with IBD pathogenesis. Regulation of this axis may be a novel option for treating IBD.}, }
@article {pmid34578211, year = {2021}, author = {Yadav, KK and Kenney, SP}, title = {Hepatitis E Virus Immunopathogenesis.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {9}, pages = {}, pmid = {34578211}, issn = {2076-0817}, support = {R21 AI151736/AI/NIAID NIH HHS/United States ; }, abstract = {Hepatitis E virus is an important emerging pathogen producing a lethal impact on the pregnant population and immunocompromised patients. Starting in 1983, it has been described as the cause for acute hepatitis transmitted via the fecal-oral route. However, zoonotic and blood transfusion transmission of HEV have been reported in the past few decades, leading to the detailed research of HEV pathogenesis. The reason behind HEV being highly virulent to the pregnant population particularly during the third trimester, leading to maternal and fetal death, remains unknown. Various host factors (immunological, nutritional, hormonal) and viral factors have been studied to define the key determinants assisting HEV to be virulent in pregnant and immunocompromised patients. Similarly, chronic hepatitis is seen particularly in solid organ transplant patients, resulting in fatal conditions. This review describes recent advances in the immunopathophysiology of HEV infections in general, pregnant, and immunocompromised populations, and further elucidates the in vitro and in vivo models utilized to understand HEV pathogenesis.}, }
@article {pmid34578169, year = {2021}, author = {Goodman-Davis, R and Figurska, M and Cywinska, A}, title = {Gut Microbiota Manipulation in Foals-Naturopathic Diarrhea Management, or Unsubstantiated Folly?.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {9}, pages = {}, pmid = {34578169}, issn = {2076-0817}, abstract = {Diarrhea in foals is a problem of significant clinical and economic consequence, and there are good reasons to believe microbiota manipulation can play an important role in its management. However, given the dynamic development of the foal microbiota and its importance in health and disease, any prophylactic or therapeutic efforts to alter its composition should be evidence based. The few clinical trials of probiotic preparations conducted in foals to date show underwhelming evidence of efficacy and a demonstrated potential to aggravate rather than mitigate diarrhea. Furthermore, recent studies have affirmed that variable but universally inadequate quality control of probiotics enables inadvertent administration of toxin-producing or otherwise pathogenic bacterial strains, as well as strains bearing transferrable antimicrobial resistance genes. Consequently, it seems advisable to approach probiotic therapy in particular with caution for the time being. While prebiotics show initial promise, an even greater scarcity of clinical trials makes it impossible to weigh the pros and cons of their use. Advancing technology will surely continue to enable more detailed and accurate mapping of the equine adult and juvenile microbiota and potentially elucidate the complexities of causation in dysbiosis and disease. In the meantime, fecal microbiota transplantation may be an attractive therapeutic shortcut, allowing practitioners to reconstruct a healthy microbiota even without fully understanding its constitution.}, }
@article {pmid34576740, year = {2021}, author = {Kouidhi, S and Souai, N and Zidi, O and Mosbah, A and Lakhal, A and Ben Othmane, T and Belloumi, D and Ben Ayed, F and Asimakis, E and Stathopoulou, P and Cherif, A and Tsiamis, G}, title = {High Throughput Analysis Reveals Changes in Gut Microbiota and Specific Fecal Metabolomic Signature in Hematopoietic Stem Cell Transplant Patients.}, journal = {Microorganisms}, volume = {9}, number = {9}, pages = {}, pmid = {34576740}, issn = {2076-2607}, support = {KA107//Erasmus+/ ; LR11ES31//LBVBGR/ ; }, abstract = {There is mounting evidence for the emerging role of gut microbiota (GM) and its metabolites in profoundly impacting allogenic hematopoietic stem cell transplantation (allo-HSCT) and its subsequent complications, mainly infections and graft versus host-disease (GvHD). The present study was performed in order to investigate changes in GM composition and fecal metabolic signature between transplant patients (n = 15) and healthy controls (n = 18). The intestinal microbiota was characterized by NGS and gas chromatography-mass spectrometry was employed to perform untargeted analysis of fecal metabolites. We found lower relative abundances of Actinobacteria, Firmicutes, and Bacteroidetes and a higher abundance of Proteobacteria phylum after allo-HSCT. Particularly, the GvHD microbiota was characterized by a lower relative abundance of the short-chain fatty acid-producing bacteria, namely, the Feacalibacterium, Akkermansia, and Veillonella genera and the Lachnospiraceae family, and an enrichment in multidrug-resistant bacteria belonging to Escherichia, Shigella, and Bacteroides. Moreover, network analysis showed that GvHD was linked to a higher number of positive interactions of Blautia and a significant mutual-exclusion rate of Citrobacter. The fecal metabolome was dominated by lipids in the transplant group when compared with the healthy individuals (p < 0.05). Overall, 76 metabolites were significantly altered within transplant recipients, of which 24 were selected as potential biomarkers. Furthermore, the most notable altered metabolic pathways included the TCA cycle; butanoate, propanoate, and pyruvate metabolisms; steroid biosynthesis; and glycolysis/gluconeogenesis. Specific biomarkers and altered metabolic pathways were correlated to GvHD onset. Our results showed significant shifts in gut microbiota structure and fecal metabolites characterizing allo-HSCT.}, }
@article {pmid34575166, year = {2021}, author = {Stojek, M and Jabłońska, A and Adrych, K}, title = {The Role of Fecal Microbiota Transplantation in the Treatment of Inflammatory Bowel Disease.}, journal = {Journal of clinical medicine}, volume = {10}, number = {18}, pages = {}, pmid = {34575166}, issn = {2077-0383}, abstract = {The exact pathogenesis of inflammatory bowel disease (IBD) is still not completely understood. It is hypothesized that a genetic predisposition leads to an exaggerated immune response to an environmental trigger, leading to uncontrolled inflammation. As there is no known causative treatment, current management strategies for inflammatory bowel disease focus on correcting the excessive immune response to environmental (including microbial) triggers. In recent years, there has been growing interest in new avenues of treatment, including targeting the microbial environment itself. Fecal microbiota transplantation (FMT) is a novel treatment modality showing promising results in early studies. The article discusses the rationale for the use of FMT in inflammatory bowel disease and the yet-unresolved questions surrounding its optimal use in practice.}, }
@article {pmid34573670, year = {2021}, author = {Rosa, F and Michelotti, TC and St-Pierre, B and Trevisi, E and Osorio, JS}, title = {Early Life Fecal Microbiota Transplantation in Neonatal Dairy Calves Promotes Growth Performance and Alleviates Inflammation and Oxidative Stress during Weaning.}, journal = {Animals : an open access journal from MDPI}, volume = {11}, number = {9}, pages = {}, pmid = {34573670}, issn = {2076-2615}, support = {SD00H612-16//U.S. Department of Agriculture/ ; }, abstract = {This study aimed to evaluate the effects of early life fecal microbiota transplantation (FMT) on the health and performance of neonatal dairy calves. The donor was selected based on health and production records and fecal material testing negative for infectious pathogens. Sixteen healthy newborn Holstein calves were randomized to either a baseline nutritional program (CON) or 1×/d inoculations with 25 g of fecal donor material (FMT) mixed in the milk replacer (n = 8/TRT) from 8 to 12 days of age. Blood and fecal samples were collected weekly, and calves were weaned at 7 weeks of age. A TRT × Week interaction was observed in haptoglobin, which was reflected in a positive quadratic effect in FMT calves but not in CON. A trend for a TRT × Week interaction was observed in the liver function biomarker paraoxonase, which resulted in greater paraoxonase in FMT calves than CON at three weeks of age. Fecal microbial community analysis revealed a significant increase in the alpha-diversity between week 1 and week 5 for the FMT calves. These results suggest that early life FMT in neonatal calves has positive effects in mediating the inflammatory response and gut microbial maturation.}, }
@article {pmid34573058, year = {2021}, author = {de la Visitación, N and Robles-Vera, I and Moleón, J and González-Correa, C and Aguilera-Sánchez, N and Toral, M and Gómez-Guzmán, M and Sánchez, M and Jiménez, R and Martin-Morales, N and O'Valle, F and Romero, M and Duarte, J}, title = {Gut Microbiota Has a Crucial Role in the Development of Hypertension and Vascular Dysfunction in Toll-like Receptor 7-Driven Lupus Autoimmunity.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {10}, number = {9}, pages = {}, pmid = {34573058}, issn = {2076-3921}, support = {SAF2017-84894-R//Ministerio de Econom&#xed;a y Competitividad/ ; PID2020-116347RB-I00//Ministerio de Ciencia e Innovaci&#xf3;n/ ; P20_00193//Consejer&#xed;a de Econom&#xed;a, Innovaci&#xf3;n, Ciencia y Empleo, Junta de Andaluc&#xed;a/ ; CTS 164//Consejer&#xed;a de Econom&#xed;a, Innovaci&#xf3;n, Ciencia y Empleo, Junta de Andaluc&#xed;a/ ; }, abstract = {Our group has investigated the involvement of gut microbiota in hypertension in a murine model of systemic lupus erythematosus induced by Toll-like receptor (TLR)-7 activation. Female BALB/c mice were randomly assigned to four experimental groups: an untreated control (CTR), a group treated with the TLR7 agonist imiquimod (IMQ), IMQ-treated with vancomycin, and IMQ-treated with a cocktail of broad-spectrum antibiotics. We carried out faecal microbiota transplant (FMT) from donor CTR or IMQ mice to recipient IMQ or CTR animals, respectively. Vancomycin inhibited the increase in blood pressure; improved kidney injury, endothelial function, and oxidative stress; and reduced T helper (Th)17 infiltration in aortas from IMQ-treated mice. The rise in blood pressure and vascular complications present in IMQ mice were also observed in the CTR mice recipients of IMQ microbiota. Reduced relative populations of Sutterella and Anaerovibrio were associated with high blood pressure in our animals, which were increased after stool transplantation of healthy microbiota to IMQ mice. The reduced endothelium-dependent vasodilator responses to acetylcholine induced by IMQ microbiota were normalized after interleukin-17 neutralization. In conclusion, gut microbiota plays a role in the TLR7-driven increase in Th17 cell, endothelial dysfunction, vascular inflammation, and hypertension. The vascular changes induced by IMQ microbiota were initiated by Th17 infiltrating the vasculature.}, }
@article {pmid34572894, year = {2021}, author = {Kaźmierczak-Siedlecka, K and Skonieczna-Żydecka, K and Biliński, J and Roviello, G and Iannone, LF and Atzeni, A and Sobocki, BK and Połom, K}, title = {Gut Microbiome Modulation and Faecal Microbiota Transplantation Following Allogenic Hematopoietic Stem Cell Transplantation.}, journal = {Cancers}, volume = {13}, number = {18}, pages = {}, pmid = {34572894}, issn = {2072-6694}, abstract = {Nowadays, allogenic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy that is mainly recommended for hematologic malignancies. However, complications (such as graft-versus-host disease, mucositis, disease relapse, and infections) associated with the HSCT procedure contribute to the development of gut microbiota imbalance, gut-barrier disruption, and increased intestinal permeability. In the present narrative review, the crosstalk between gut microbiota products and intestinal homeostasis is discussed. Notably, gut-microbiota-related aspects have an impact on patients' clinical outcomes and overall survival. In accordance with the most recent published data, gut microbiota is crucial for the treatment effectiveness of many diseases, not only gastrointestinal cancers but also hematologic malignancies. Therefore, it is necessary to indicate a therapeutic method allowing to modulate gut microbiota in HSCT recipients. Currently, fecal microbiota transplantation (FMT) is the most innovative method used to alter/restore gut microbiota composition, as well as modulate its activity. Despite the fact that some previous data have shown promising results, the knowledge regarding FMT in HSCT is still strongly limited, except for the treatment of Clostridium difficile infection. Additionally, administration of prebiotics, probiotics, synbiotics, and postbiotics can also modify gut microbiota; however, this strategy should be considered carefully due to the high risk of fungemia/septicemia (especially in case of fungal probiotics).}, }
@article {pmid34571151, year = {2021}, author = {Yu, DH and Ying, N and Lian, ZH and Fa, YQ}, title = {The Alteration human of gut microbiota and metabolites before and after renal transplantation.}, journal = {Microbial pathogenesis}, volume = {160}, number = {}, pages = {105191}, doi = {10.1016/j.micpath.2021.105191}, pmid = {34571151}, issn = {1096-1208}, mesh = {Feces ; *Gastrointestinal Microbiome ; Humans ; *Kidney Transplantation ; RNA, Ribosomal, 16S/genetics ; Transplant Recipients ; }, abstract = {BACKGROUND: Recent studies have revealed that gut microbiota play an important part in the regulation of the immune function. With the development of newer detection methods, our cognition of the human gut microbiota continues to evolve with startling speed, but our understanding of the changes in the structure and function of gut microbiota before and after renal transplantation and the practical applications of this knowledge are still in their infancy.<br><br>METHODS: We prospectively recruited 10 renal transplant recipients and collected serial fecal specimens (N&#xa0;=&#xa0;30) before the operation, and on the 7th and 30th day after the operation, and characterized their gut microbiota structure through deep sequencing of the 16S rRNA V4-V5 variable region and analyzed the presence of metabolites using LC-MS methods.<br><br>RESULTS: A decrease in the relative abundance of overall gut microbiota was detected in post-transplantation samples compared to that in pre-transplantation samples. Principal coordinate analysis (PCoA) inhibited a obvious separation between the three groups, and the linear discriminant analysis effect size (LEfSe) method showed that Clostridiales, Clostridia, Ruminococcaceae, Faecalibacterium, and Veillonellaceae were all significantly more abundant in the fecal specimens from the pre-transplantation group while Bacilli, Enterococcaceae, and Enterococcus were significantly more abundant in the fecal specimens from the four weeks post-transplantation group. Anaerostipes and Clostridia-bacterium were detected in the fecal samples from the one week post-transplantation group. Analysis of community composition did not reveal any significant difference between the pre-transplantation group and the post-transplantation group. The metabolic profiling of the volunteers before renal transplantation were distinct from the post-transplantation profiling, which gather together in PCA (Fig. 4A). After renal transplantation, the metabolic profiling of post-transplantation specimens revealed marked diversity and complexity.<br><br>CONCLUSIONS: Our research indicated remarkable variations in the gut microbiota and metabolites following renal transplantation, and that the gut microbiota and metabolites of patients with uremia were relatively stable and showed reasonable concordance. Distinct microbial compositions and metabolites were observed in patients after transplantation.}, }
@article {pmid34569012, year = {2021}, author = {Katiyar, M and Gulati, R and Pagal, S and Rajkumari, N and Singh, R}, title = {Molecular detection of Cystoisospora belli by single-run polymerase chain reaction in stool samples.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {40}, number = {5}, pages = {512-518}, pmid = {34569012}, issn = {0975-0711}, mesh = {Child ; Cross-Sectional Studies ; Diarrhea/diagnosis ; Feces ; Humans ; *Isosporiasis/diagnosis ; Polymerase Chain Reaction ; Reproducibility of Results ; }, abstract = {INTRODUCTION: Cystoisospora belli (C. belli) is the only pathogenic species of the Cystoisospora genus responsible for severe diarrhea in immunocompromised patients. Most common microscopic method of diagnosis is less sensitive due to intermittent shedding of oocysts. We developed a new single-run polymerase chain reaction (PCR)-based diagnostic assay for C. belli.<br><br>METHODS: A new single-run PCR-based diagnostic assay was standardized for the detection of C. belli. Diagnostic reproducibility and repeatability of the PCR assay were evaluated. A cross-sectional analytical study was done on a total of 354 stool samples collected from 331 immunocompromised patients with diarrhea. All the stool samples were tested for the presence of oocysts of C. belli and were also tested by our new PCR assay for C. belli. Three of the representative PCR products were confirmed by sequencing. Fisher's exact test was used to compare the two proportions.<br><br>RESULTS: Microscopy detected C. belli in 11/354 (3.1%) of stool samples, and the new PCR-based assay detected C. belli in 16/354 (4.5%). The new single-run PCR-based assay detected C. belli in all the stool samples which were tested positive by microscopy and additionally detected C. belli in five stool samples. The developed PCR assay detected statistically significant proportion of C. belli (p < 0.001) as compared to microscopy. The 795 base pair PCR product from one microscopy positive stool sample and two microscopy negative stool samples were confirmed by sequencing.<br><br>CONCLUSION: Our newly developed single-run PCR-based detection assay for C. belli is robust and reproducible. It may be used for molecular diagnosis of cystoisosporiasis especially in transplant, pediatrics, and human immunodeficiency virus (HIV) positive patients.}, }
@article {pmid34568329, year = {2021}, author = {Wang, Q and Yi, S and Su, G and Du, Z and Pan, S and Huang, X and Cao, Q and Yuan, G and Kijlstra, A and Yang, P}, title = {Changes in the Gut Microbiome Contribute to the Development of Behcet's Disease via Adjuvant Effects.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {716760}, pmid = {34568329}, issn = {2296-634X}, abstract = {Behcet's disease (BD) is associated with considerable gut microbiome changes. However, it still remains unknown how the composition of the gut microbiome exactly affects the development of this disease. In this study, transplantation of stool samples from patients with active ocular BD to mice via oral gavage was performed. This resulted in decreases of three short chain fatty acids (SCFAs) including butyric acid, propionic acid and valeric acid in the feces of the BD-recipient group. Intestinal barrier integrity of mice receiving BD feces was damaged as shown by a decreased expression of tight junction proteins and was associated with the release of Lipopolysaccharides (LPS) in the circulation. The mice also showed a higher frequency of splenic neutrophils as well as an enrichment of genes associated with innate immune responses in the neutrophils and CD4 + T cells as identified by single cell RNA sequencing. Analysis of neutrophils and T cells functions in these mice showed an enhanced mesenteric lymph node and splenic Th1 and Th17 cell differentiation in association with activation of neutrophils. Transplantation of BD feces to mice and subsequent induction of experimental uveitis (EAU) or encephalomyelitis (EAE) led to an exacerbation of disease in both models, suggesting a microbial adjuvant effect. These findings suggest that the gut microbiome may regulate an autoimmune response via adjuvant effects including increased gut permeability and enhancement of innate immunity.}, }
@article {pmid34567271, year = {2021}, author = {Liu, Y and Alnababtah, K and Cook, S and Yu, Y}, title = {Healthcare providers' perception of faecal microbiota transplantation with clostridium difficile infection and inflammatory bowel disease: a quantitative systematic review.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211042679}, pmid = {34567271}, issn = {1756-283X}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD) are global gastroenterological diseases that cause considerable burden on human health, healthcare systems, and society. Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides Difficile Infection (rCDI) and a promising therapy for IBD. However, indication for FMT in IBD is still unofficial. Consequently, the National Institute for Health and Care Excellence (NICE) is seeking healthcare providers' advice on whether to update FMT guidelines.<br><br>METHODS: A systematic review methodology was adopted for this study. Five databases (CINAHL, MEDLINE, Cochrane Library, Scopus, Web of Science) and grey literature were systematically searched for English language literature to 14 May 2021. The quality of the included studies was then appraised using the Institute for Public Health Sciences cross-sectional studies tool, after which the findings of the studies were narratively synthesised.<br><br>RESULTS: Thirteen cross-sectional studies with 4110 validated questionnaire responses were included. Narrative synthesis found that 39.43% of respondents were familiar with FMT (N&#x2009;=&#x2009;3746, 95%CI&#x2009;=&#x2009;37.87%-41%), 58.81% of respondents would recommend FMT to their patients (N&#x2009;=&#x2009;1141, 95%CI&#x2009;=&#x2009;55.95%-61.67%), 66.67% of respondents considered lack of clinical evidence was the greatest concern regarding FMT (N&#x2009;=&#x2009;1941, 95%CI&#x2009;=&#x2009;64.57%-68.77%), and 40.43% respondents would not implement FMT due to concerns about infection transmission (N&#x2009;=&#x2009;1128, 95%CI&#x2009;=&#x2009;37.57%-43.29%).<br><br>CONCLUSION: Healthcare providers' knowledge of FMT is relatively low and education is an effective strategy to improve it. As knowledge of FMT increases, willingness to recommend it also increases. Strengthening FMT clinical efficacy and reducing infection can enhance its public acceptance, application and popularity. However, further research is required to explore the donor screening procedure.}, }
@article {pmid34560321, year = {2021}, author = {Zuo, T and Wu, X and Wen, W and Lan, P}, title = {Gut Microbiome Alterations in COVID-19.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {19}, number = {5}, pages = {679-688}, pmid = {34560321}, issn = {2210-3244}, mesh = {Bacteria ; *COVID-19/complications ; Fungi ; *Gastrointestinal Microbiome ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, the gut microbiome in COVID-19 has garnered substantial interest, given its significant roles in human health and pathophysiology. Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome. Overall, the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19, together with a decrease in gut microbiome diversity. Beyond the existence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria, fungi, and eukaryotic viruses, which are also associated with disease severity and presentation. Meanwhile, a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19. Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with 'long COVID' (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the reassembly of the gut microbiome post COVID-19. Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection, as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.}, }
@article {pmid34557546, year = {2021}, author = {Mihaescu, A and Augustine, AM and Khokhar, HT and Zafran, M and Masood, SSME and Gilca-Blanariu, GE and Covic, A and Nistor, I}, title = {Clostridioides difficile Infection in Patients with Chronic Kidney Disease: A Systematic Review.}, journal = {BioMed research international}, volume = {2021}, number = {}, pages = {5466656}, pmid = {34557546}, issn = {2314-6141}, mesh = {Clostridium Infections/*complications/prevention &amp; control/therapy ; Humans ; Outcome Assessment, Health Care ; Randomized Controlled Trials as Topic ; Renal Insufficiency, Chronic/*complications/*microbiology ; }, abstract = {Clostridioides difficile infection (CDI) is a health issue of utmost significance in Europe and North America, due to its high prevalence, morbidity, and mortality rate. The clinical spectrum of CDI is broad, ranging from asymptomatic to deadly fulminant colitis. When associated with chronic kidney disease (CKD), CDI is more prevalent and more severe than in the general population, due to specific risk factors such as impaired immune system, intestinal dysmotility, high antibiotic use leading to disturbed microbiota, frequent hospitalization, and PPI use. We performed a systematic review on the issue of prevention and treatment of CDI in the CKD population, analysing the suitable randomized controlled cohort studies published between 2000 and 2021. The results show that the most important aspect of prevention is isolation and disinfection with chlorine-based solution and hydrogen peroxide vapour to stop the spread of bacteria. In terms of prevention, using Lactobacillus plantarum (LP299v) proved to be more efficient than disinfection measures in transplant patients, leading to higher cure rates and less recurrent episodes of CDI. Treatment with oral fidaxomycin is more effective than with oral vancomycin for the initial episode of CDI in CKD patients. Faecal microbiota transplantation (FMT) is more effective than vancomycin in recurrent CDI in CKD patients. More large-sample RCTs are necessary to conclude on the best treatment and prevention strategy of CDI in CKD patients.}, }
@article {pmid34557498, year = {2021}, author = {Liptak, R and Gromova, B and Gardlik, R}, title = {Fecal Microbiota Transplantation as a Tool for Therapeutic Modulation of Non-gastrointestinal Disorders.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {665520}, pmid = {34557498}, issn = {2296-858X}, abstract = {Fecal microbiota transplantation has been primarily investigated as a therapeutic tool for a number of gut disorders. Optimistic results from clinical studies on Clostridium difficile infection, inflammatory bowel disease and irritable bowel syndrome have stimulated the expansion of possible indications in which FMT might represent a game changing approach. Microbial dysbiosis was shown in a number of non-gastrointestinal disorders. Moreover, FMT was proven to be effective in therapy of numerous animal models of disease. However, only a proportion of these disorders have been addressed in clinical studies using FMT. These include obesity, non-alcoholic fatty liver disease, cardiovascular inflammation and neurological disorders such as autism, depression and Parkinson's disease. Results from preclinical and clinical studies also outlined possible molecular mechanisms that contribute to alleviation of the disease. These range from increasing the circulating levels of microbial metabolites (trimethylamine N-oxide, lipopolysaccharide, short chain fatty acids) to stimulation of the enteric nervous system. Several methodological shortcomings are still to be addressed; however, positive results of the clinical studies indicate that further investigation of FMT as a therapeutic tool for non-gastrointestinal disorders can be expected in upcoming years.}, }
@article {pmid34557102, year = {2021}, author = {Sun, Z and Li, J and Wang, W and Liu, Y and Liu, J and Jiang, H and Lu, Q and Ding, P and Shi, R and Zhao, X and Yuan, W and Tan, X and Shi, X and Xing, Y and Mao, T}, title = {Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {738152}, pmid = {34557102}, issn = {1663-9812}, abstract = {Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/β-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.}, }
@article {pmid34555295, year = {2022}, author = {Shan, Y and Lee, M and Chang, EB}, title = {The Gut Microbiome and Inflammatory Bowel Diseases.}, journal = {Annual review of medicine}, volume = {73}, number = {}, pages = {455-468}, pmid = {34555295}, issn = {1545-326X}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DK113788/DK/NIDDK NIH HHS/United States ; RC2 DK122394/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; R01 DK047722/DK/NIDDK NIH HHS/United States ; }, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases ; *Microbiota ; }, abstract = {Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports a bidirectional relationship between disease progression and changes in microbiota membership and function. Thus, the study of the gut microbiome and host-microbe interactions should provide critical insights into disease pathogenesis as well as leads for developing microbiome-based diagnostics and interventions for IBD. In this article, we review the most recent advances in understanding the relationship between the gut microbiota and IBD and highlight the importance of going beyond establishing description and association to gain mechanistic insights into causes and consequences of IBD. The review aims to contextualize recent findings to form conceptional frameworks for understanding the etiopathogenesis of IBD and for the future development of microbiome-based diagnostics and interventions.}, }
@article {pmid34554118, year = {2021}, author = {de Stefano, MC and Mazzanti, B and Vespasiano, F and Cammarota, G and Ianiro, G and Masucci, L and Sanguinetti, M and Gasbarrini, A and Lombardini, L and Cardillo, M}, title = {The Italian National Faecal Microbiota Transplantation Program: a coordinated effort against Clostridioides difficile infection.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {57}, number = {3}, pages = {239-243}, doi = {10.4415/ANN_21_03_07}, pmid = {34554118}, issn = {2384-8553}, mesh = {Adult ; Aged ; Aged, 80 and over ; COVID-19 ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Italy ; Male ; Middle Aged ; Prospective Studies ; Young Adult ; }, abstract = {Clostridioides (previously Clostridium) difficile infection (CDI) is a common cause of antibiotic-associated diarrhea, whose symptoms range from mild diarrhea to life-threatening pseudomembranous colitis. CDI is characterized by significant recurrence rate following initial resolution and recurrent C. difficile infection (rCDI) represents an onerous burden for the healthcare systems. Conventional antibiotic-based approaches are generally used for the treatment of rCDI but the effective therapy remains elusive. Recently, the faecal microbiota transplantation (FMT) has emerged as an alternative therapeutic strategy against rCDI, with high treatment success rate. In 2018, the Italian National FMT Program was launched, with the aim to provide high quality standards in FMT application to adults with rCDI not responding to antibiotic therapy. Here, we sketch out the key characteristics and the progress of the Italian National FMT Program during the COVID-19 pandemic.}, }
@article {pmid34552222, year = {2021}, author = {Chaudhari, SN and McCurry, MD and Devlin, AS}, title = {Chains of evidence from correlations to causal molecules in microbiome-linked diseases.}, journal = {Nature chemical biology}, volume = {17}, number = {10}, pages = {1046-1056}, pmid = {34552222}, issn = {1552-4469}, support = {R01 DK126855/DK/NIDDK NIH HHS/United States ; R35 GM128618/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Infective Agents/pharmacology ; Communicable Diseases/*microbiology ; Fecal Microbiota Transplantation ; Germ-Free Life ; Host Microbial Interactions/*physiology ; Humans ; Microbiota/*physiology ; }, abstract = {Human-associated microorganisms play a vital role in human health, and microbial imbalance has been linked to a wide range of disease states. In this Review, we explore recent efforts to progress from correlative studies that identify microorganisms associated with human disease to experiments that establish causal relationships between microbial products and host phenotypes. We propose that successful efforts to uncover phenotypes often follow a chain of evidence that proceeds from (1) association studies; to (2) observations in germ-free animals and antibiotic-treated animals and humans; to (3) fecal microbiota transplants (FMTs); to (4) identification of strains; and then (5) molecules that elicit a phenotype. Using this experimental 'funnel' as our guide, we explore how the microbiota contributes to metabolic disorders and hypertension, infections, and neurological conditions. We discuss the potential to use FMTs and microbiota-inspired therapies to treat human disease as well as the limitations of these approaches.}, }
@article {pmid34552194, year = {2022}, author = {Brunse, A and Deng, L and Pan, X and Hui, Y and Castro-Mejía, JL and Kot, W and Nguyen, DN and Secher, JB and Nielsen, DS and Thymann, T}, title = {Fecal filtrate transplantation protects against necrotizing enterocolitis.}, journal = {The ISME journal}, volume = {16}, number = {3}, pages = {686-694}, pmid = {34552194}, issn = {1751-7370}, mesh = {Animals ; *Enterocolitis, Necrotizing/microbiology/prevention &amp; control ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; Infant, Premature ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; Swine ; }, abstract = {Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventive therapy, but the transfer of pathogenic microbes or toxic compounds raise concern. Removal of bacteria from donor feces by micropore filtering may reduce this risk of bacterial infection, while residual bacteriophages could maintain the NEC-preventive effects. We aimed to assess preclinical efficacy and safety of fecal filtrate transplantation (FFT). Using fecal material from healthy suckling piglets, we compared rectal FMT administration (FMT, n = 16) with cognate FFT by either rectal (FFTr, n = 14) or oro-gastric administration (FFTo, n = 13) and saline (CON, n = 16) in preterm, cesarean-delivered piglets as models for preterm infants. We assessed gut pathology and analyzed mucosal and luminal bacterial and viral composition using 16S rRNA gene amplicon and meta-virome sequencing. Finally, we used isolated ileal mucosa, coupled with RNA-Seq, to gauge the host response to the different treatments. Oro-gastric FFT completely prevented NEC, which was confirmed by microscopy, whereas FMT did not perform better than control. Oro-gastric FFT increased viral diversity and reduced Proteobacteria relative abundance in the ileal mucosa relative to control. An induction of mucosal immunity was observed in response to FMT but not FFT. As preterm infants are extremely vulnerable to infections, rational NEC-preventive strategies need incontestable safety profiles. We show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects.}, }
@article {pmid34550085, year = {2021}, author = {Chinna Meyyappan, A and Sgarbossa, C and Vazquez, G and Bond, DJ and Müller, DJ and Milev, R}, title = {The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression: Protocol for a Phase 2, Double-Blind, Placebo-Controlled Study.}, journal = {JMIR research protocols}, volume = {10}, number = {9}, pages = {e31439}, pmid = {34550085}, issn = {1929-0748}, abstract = {BACKGROUND: The gut-brain axis is a bidirectional signaling pathway between the gastrointestinal tract and the brain; it is being studied because of its potential influence in mediating mood, anxiety, and other neuropsychiatric symptoms. Previous research examining the effects of gut microbiota on neuropsychiatric disorders suggests that gut repopulation treatments such as probiotics, microbe therapy, and fecal microbiota transplantation show promising results in treating symptoms of anxiety and depression. This study explores the use of an alternative gut repopulation treatment to fecal microbiota transplantation, known as Microbial Ecosystem Therapeutic (MET)-2, as an intervention against symptoms of depression. MET-2 is a daily, orally administered capsule containing 40 bacterial strains purified from a single healthy donor.<br><br>OBJECTIVE: The primary aim of this study is to assess changes in mood in people with major depression that occur pre-, post-, and during the administration of MET-2. The secondary aims are to assess changes in anxiety symptoms, blood biomarker concentrations, and the level of repopulation of healthy gut bacteria as a response to treatment.<br><br>METHODS: In this study, we will recruit 60 adults aged between 18 and 45 years old with major depression and randomly assign them to treatment or placebo groups. Patients in the treatment group will receive MET-2 once a day for 6 weeks, whereas patients in the placebo group will receive a matching placebo for 6 weeks. Participants will complete biweekly visits during the treatment period and a follow-up visit at 2 weeks post treatment. As a primary outcome measure, participants' mood will be assessed using the Montgomery-Asberg Depression Rating Scale. Secondary outcome measures include changes in mood, anxiety, early stress, gastrointestinal symptoms, and tolerability of MET-2 treatment using a series of clinical scales and changes in blood markers, particularly immunoglobulins (Igs; IgA, IgG, and IgM) and inflammatory markers (C-reactive protein, tumor necrosis factor-&#x3b1;, transforming growth factor-&#x3b2;, interleukin-6, and interleukin-10). Changes in the relative abundance, diversity, and level of engraftment in fecal samples will be assessed using 16S rRNA sequencing. All data will be integrated to identify biomarkers that could indicate disease state or predict improvement in depressive symptoms in response to MET-2 treatment.<br><br>RESULTS: Given the association between the gut microbiome and depression, we hypothesized that participants receiving MET-2 would experience greater improvement in depressive symptoms than those receiving placebo owing to the recolonization of the gut microbiome with healthy bacteria modulating the gut-brain axis connection.<br><br>CONCLUSIONS: This study is the first of its kind to evaluate the safety and efficacy of a microbial therapy such as MET-2 in comparison with placebo for major depressive disorder. We hope that this study will also reveal the potential capabilities of microbial therapies to treat other psychiatric illnesses and mood disorders.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT04602715; https://clinicaltrials.gov/ct2/show/NCT04602715.<br><br>DERR1-10.2196/31439.}, }
@article {pmid34549762, year = {2021}, author = {Yan, X and Wang, Y and Ren, XY and Liu, XY and Ma, JM and Song, RL and Wang, XH and Dong, Y and Yu, AX and Fan, QQ and Wei, J and She, GM}, title = {Gut dysbiosis correction contributes to the hepatoprotective effects of Thymus quinquecostatus Celak extract against alcohol through the gut-liver axis.}, journal = {Food &amp; function}, volume = {12}, number = {20}, pages = {10281-10290}, doi = {10.1039/d1fo01117k}, pmid = {34549762}, issn = {2042-650X}, mesh = {Animals ; Dysbiosis/*drug therapy/metabolism ; Ethanol/adverse effects ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/drug effects ; Lipopolysaccharides/metabolism ; Liver/metabolism ; Liver Diseases, Alcoholic/metabolism/pathology/*prevention &amp; control ; Male ; Mice ; Mice, Inbred C57BL ; Plant Extracts/*pharmacology ; Protective Agents/*pharmacology ; Reactive Oxygen Species/metabolism ; Thymus Plant/*chemistry ; Toll-Like Receptor 4/metabolism ; }, abstract = {Alcoholic liver disease (ALD) is a major health issue globally due to the consumption of alcoholic beverages. Thymus quinquecostatus Celak is a food additive and an edible herb that is widely used in Asia and possesses hepatoprotective activity, but the underlying mechanisms behind this protective activity are not completely understood. The purpose of this study was to investigate the hepatoprotective effects of Thymus quinquecostatus Celak extract (TQE) against ALD as well as the underlying mechanism based on gut microbiota and the gut-liver axis. TQE supplementation markedly alleviated chronic alcohol-induced liver injury in C57 mice. TQE also ameliorated gut barrier dysfunction induced by alcohol. Consequently, the activation of the lipopolysaccharide (LPS) translocation-mediated TLR4 pathway and the subsequent inflammatory response and ROS overproduction in the liver were suppressed. Meanwhile, alcohol-induced gut microbiota dysbiosis was also corrected by TQE. To further investigate the contribution of gut dysbiosis correction to the beneficial effects of TQE on ALD, a fecal microbiota transplantation study was conducted. TQE-manipulated gut microbiota transplantation markedly counteracted the alcohol-induced gut dysbiosis in the recipient mice. In parallel with gut dysbiosis correction, liver damage was partly ameliorated in the recipient mice. Gut barrier dysfunction, endotoxemia, TLR4 pathway induction as well as downstream inflammatory response and ROS overproduction were also partly suppressed due to gut dysbiosis correction in alcohol-fed recipient mice. In summary, these results suggest that gut dysbiosis correction contributes to the hepatoprotective effects of TQE against alcohol through the gut-liver axis.}, }
@article {pmid34544375, year = {2021}, author = {Koo, H and Morrow, CD}, title = {Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {251}, pmid = {34544375}, issn = {1471-2180}, mesh = {Clostridium Infections/*prevention &amp; control ; Fecal Microbiota Transplantation/*methods/standards ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics/*physiology ; Humans ; Immunotherapy/*adverse effects ; Longitudinal Studies ; Melanoma/immunology/therapy ; *Symbiosis ; }, abstract = {BACKGROUND: To understand inter-individual variability of fecal microbe transplantation (FMT) to enhance anti-PD-1 immunotherapy (IT) for melanoma, we analyzed the data sets from two recent publications with a microbial strain-tracking tool to determine if donor strains were dominant in the recipient feces following FMT.<br><br>RESULTS: Analysis of the Baruch et al. data set found that the presence of commensal donor microbes in recipient feces post-FMT did not correlate with the patient response to IT. From the Davar et al., data set, we found 4 patients that responded to IT had donor's related strain post-FMT, while 2 patients that did not respond to the IT also had donor's strain post-FMT. Importantly, we identified no donor microbes in the feces in one recipient post-FMT that responded to IT. Furthermore, in depth analysis from two patients who responded to IT revealed both donor and recipient strains at different times post-FMT. Colonization of the gastrointestinal tract niches is important for the interaction with the host immune system. Using a separate data set, we show that mucosa from the cecum, transverse colon, and sigmoid colon share strains, providing a large reservoir of niches containing recipient microbes.<br><br>CONCLUSIONS: We demonstrated using strain-tracking analysis individual variation with the respect to the presence of fecal dominant donor microbes in the recipient following FMT that did not correlate with the response to anti-PD-1 immunotherapy. The inter-individual differences of FMT to enhance IT might be explained by the variability of the donor microbes to occupy and outcompete recipient microbes for the gastrointestinal niches. The result from our study supports the use of new approaches to clear the niches in the gastrointestinal tract to promote donor colonization to reduce inter-individual variability of IT for melanoma and potentially other cancers.}, }
@article {pmid34543718, year = {2022}, author = {Wah-Suárez, MI and Vázquez, MAM and Bosques-Padilla, FJ}, title = {Inflammatory bowel disease: The role of commensal microbiome in immune regulation.}, journal = {Gastroenterologia y hepatologia}, volume = {45}, number = {8}, pages = {626-636}, doi = {10.1016/j.gastrohep.2021.08.008}, pmid = {34543718}, issn = {0210-5705}, mesh = {Anti-Bacterial Agents/therapeutic use ; Chronic Disease ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; *Inflammatory Bowel Diseases/drug therapy ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {The incidence of inflammatory bowel disease (IBD) is increasing. Microbiome is one of the most important factors in its development and affects the different clinical outcomes of IBD patients depending on its composition and different alterations. We conducted a systematic review to discuss the association between microbiome and IBD in terms of immune regulation, and therapies that can modify microbiota. A comprehensive systematic literature search was performed through April 2020 in PubMed, Web of Science, the Cochrane Library, and clinicaltrials.gov. Inclusion criteria required IBD immune regulation and alternate therapeutics for IBD. This analysis helps explain the multifactorial origin of microbiome diversity including normal immune regulation, immune pathophysiology of IBD, and shows the evidence of several therapeutic targets to change microbiome in patients with IBD, such as prebiotics, probiotics, antibiotics, fecal microbiota transplant, and others.}, }
@article {pmid34539138, year = {2021}, author = {Kang, YB and Cai, Y}, title = {Faecal microbiota transplantation enhances efficacy of immune checkpoint inhibitors therapy against cancer.}, journal = {World journal of gastroenterology}, volume = {27}, number = {32}, pages = {5362-5375}, pmid = {34539138}, issn = {2219-2840}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors ; *Neoplasms/drug therapy ; Radioimmunotherapy ; }, abstract = {Even though immune checkpoint inhibitors (ICIs) are effective on multiple cancer types, there are still many non-responding patients. A possible factor put forward that may influence the efficacy of ICIs is the gut microbiota. Additionally, faecal microbiota transplantation may enhance efficacy of ICIs. Nevertheless, the data available in this field are insufficient, and relevant scientific work has just commenced. As a result, the current work reviewed the latest research on the association of gut microbiota with ICI treatments based on anti-programmed cell death protein 1 antibody and anti- cytotoxic T-lymphocyte-associated protein 4 antibody and explored the therapeutic potential of faecal microbiota transplantation in combination with ICI therapy in the future.}, }
@article {pmid34536490, year = {2022}, author = {Chidambaram, SB and Essa, MM and Rathipriya, AG and Bishir, M and Ray, B and Mahalakshmi, AM and Tousif, AH and Sakharkar, MK and Kashyap, RS and Friedland, RP and Monaghan, TM}, title = {Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: Tales of a vicious cycle.}, journal = {Pharmacology &amp; therapeutics}, volume = {231}, number = {}, pages = {107988}, doi = {10.1016/j.pharmthera.2021.107988}, pmid = {34536490}, issn = {1879-016X}, mesh = {Autophagy ; Brain/metabolism ; Dysbiosis/metabolism/pathology/therapy ; *Gastrointestinal Microbiome/physiology ; Humans ; Immunity ; *Neurodegenerative Diseases/metabolism ; }, abstract = {The human microbiota comprises trillions of symbiotic microorganisms and is involved in regulating gastrointestinal (GI), immune, nervous system and metabolic homeostasis. Recent observations suggest a bidirectional communication between the gut microbiota and the brain via immune, circulatory and neural pathways, termed the Gut-Brain Axis (GBA). Alterations in gut microbiota composition, such as seen with an increased number of pathobionts and a decreased number of symbionts, termed gut dysbiosis or microbial intestinal dysbiosis, plays a prominent role in the pathogenesis of central nervous system (CNS)-related disorders. Clinical reports confirm that GI symptoms often precede neurological symptoms several years before the development of neurodegenerative diseases (NDDs). Pathologically, gut dysbiosis disrupts the integrity of the intestinal barrier leading to ingress of pathobionts and toxic metabolites into the systemic circulation causing GBA dysregulation. Subsequently, chronic neuroinflammation via dysregulated immune activation triggers the accumulation of neurotoxic misfolded proteins in and around CNS cells resulting in neuronal death. Emerging evidence links gut dysbiosis to the aggravation and/or spread of proteinopathies from the peripheral nervous system to the CNS and defective autophagy-mediated proteinopathies. This review summarizes the current understanding of the role of gut microbiota in NDDs, and highlights a vicious cycle of gut dysbiosis, immune-mediated chronic neuroinflammation, impaired autophagy and proteinopathies, which contributes to the development of neurodegeneration in Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. We also discuss novel therapeutic strategies targeting the modulation of gut dysbiosis through prebiotics, probiotics, synbiotics or dietary interventions, and faecal microbial transplantation (FMT) in the management of NDDs.}, }
@article {pmid34531862, year = {2021}, author = {Islam, SMS and Ryu, HM and Sayeed, HM and Byun, HO and Jung, JY and Kim, HA and Suh, CH and Sohn, S}, title = {Eubacterium rectale Attenuates HSV-1 Induced Systemic Inflammation in Mice by Inhibiting CD83.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {712312}, pmid = {34531862}, issn = {1664-3224}, mesh = {Administration, Oral ; Adult ; Animals ; Antigens, CD/biosynthesis/genetics ; Bacteria/classification/isolation &amp; purification ; Behcet Syndrome/drug therapy/microbiology/*therapy ; Butyrates/metabolism/therapeutic use ; Colchicine/therapeutic use ; Combined Modality Therapy ; Dendritic Cells/immunology ; Disease Models, Animal ; Down-Regulation/drug effects ; *Eubacterium ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Herpes Simplex/immunology/microbiology/therapy ; Herpesvirus 1, Human/*pathogenicity ; Humans ; Immunoglobulins/biosynthesis/genetics ; Inflammation/drug therapy/*therapy ; Interleukin-17/blood ; Killer Cells, Natural/immunology ; Male ; Membrane Glycoproteins/*antagonists &amp; inhibitors/biosynthesis/genetics ; Metagenome ; Mice ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Random Allocation ; Ribotyping ; Severity of Illness Index ; CD83 Antigen ; }, abstract = {The purpose of this study was to determine whether administration of the microorganism Eubacterium rectale (E. rectale) could regulate dendritic cell (DC) activation and systemic inflammation in herpes simplex virus type 1-induced Behçet's disease (BD). E. rectale, butyrate-producing bacteria, was administered to BD mice. Peripheral blood leukocytes (PBL) and lymph node cells were isolated and analyzed by flow cytometry. 16S rRNA metagenomic analysis was performed in the feces of mice to determine the differences in the composition of the microbial population between normal and BD mice. Serum cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of DC activation marker CD83 positive cells was significantly increased in PBL of BD mice. Frequencies of CD83+ cells were also significantly increased in patients with active BD. 16S rRNA metagenomic analysis revealed different gut microbiota composition between normal and BD mice. The administration of E. rectale to BD mice reduced the frequency of CD83+ cells and significantly increased the frequency of NK1.1+ cells with the improvement of symptoms. The co-administration of colchicine and E. rectale also significantly reduced the frequency of CD83+ cells. Differences in gut microbiota were observed between normal mice and BD mice, and the administration of E. rectale downregulated the frequency of CD83, which was associated with BD deterioration. These data indicate that E. rectale could be a new therapeutic adjuvant for BD management.}, }
@article {pmid34528202, year = {2021}, author = {Asghari, A and Sadeghipour, Z and Hassanipour, S and Abbasali, Z and Ebrahimzadeh-Parikhani, H and Hashemzaei, M and Alimardani, V and Hatam, G}, title = {Association between Blastocystis sp. infection and immunocompromised patients: a systematic review and meta-analysis.}, journal = {Environmental science and pollution research international}, volume = {28}, number = {43}, pages = {60308-60328}, pmid = {34528202}, issn = {1614-7499}, support = {22097//shiraz university of medical sciences/ ; }, mesh = {*Blastocystis ; *Blastocystis Infections/epidemiology ; Feces ; Humans ; Immunocompromised Host ; Prevalence ; }, abstract = {The significance of opportunistic infections in immunocompromised patients and the enigmatic pathogenicity of Blastocystis directed us to conduct the first global systematic review and meta-analysis on Blastocystis prevalence, odds ratios (ORs), and subtypes distribution in various immunocompromised patients (HIV/AIDS, cancer and hemodialysis patients, as well as transplant recipients). The systematic searching procedure was done in Web of Science, PubMed, Scopus, and Google Scholar databases for relevant published literature until November 11, 2020. Random-effects model was utilized to calculate the weighted estimates and 95% confidence intervals (95% CIs). The computed pooled prevalence of Blastocystis inferred from 118 papers (128 datasets) on immunocompromised patients was 10.3% (95% CI: 8.7-12.2%), with 16.1% (95% CI: 11.3-22.2%), 12.5% (95% CI: 8.5-18%), 8.4% (95 % CI: 6.6-10.6%), and 6% (95% CI: 2.6-13.3%) for hemodialysis patients, cancer patients, HIV/AIDS patients, and transplant recipients, respectively. Based on 50 case-control studies (54 datasets), the highest ORs were associated with cancer [2.81 (95% CI: 1.24-6.38, P = 0.013)] and hemodialysis patients [2.78 (95% CI: 1.19-6.48, P = 0.018)]. The most frequent subtype being found in immunocompromised patients was ST3 [41.7% (95% CI: 31.4-52.7%)], followed by ST1 [31.7% (95% CI: 23.2-41.8%)] and ST2 [23.1% (95% CI: 14.8-34.1%)]. Also, the weighted frequency of Blastocystis in various subgroups (publication year, WHO regions, geographical distribution, continents, and country income) was analyzed separately. In total, the results of the present meta-analysis highlighted that one's immunodeficiency status is probably associated with an increased Blastocystis infection, underpinning strict preventive measures to be taken.}, }
@article {pmid34527093, year = {2021}, author = {Ashraf, MF and Tageldin, O and Nassar, Y and Batool, A}, title = {Fecal Microbiota Transplantation in Patients With Recurrent Clostridium difficile Infection: A Four-Year Single-Center Retrospective Review.}, journal = {Gastroenterology research}, volume = {14}, number = {4}, pages = {237-243}, pmid = {34527093}, issn = {1918-2805}, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is a common cause of hospital and community-acquired diarrhea with an annual incidence of 453,000 cases in the USA. The white race, female gender, and age over 65 years are known risk factors. Recurrence of CDI is a major problem in patients taking antibiotics for prolonged periods. These patients are observed to have reduced diversity of the intestinal microbiome. Fecal microbiota transplantation (FMT) can restore the healthy flora in the gut, thus breaking the cycle of recurrent infection. Our study aimed to analyze the efficacy of FMT and the recurrence of CDI after FMT. We also aimed to investigate the effects of comorbidities on the outcome of FMT.<br><br>METHODS: After obtaining approval from the institutional review board, we included 64 patients who had received FMT at our institution from October 2015 to November 2019. All the patients over 16 years of age in both inpatient and outpatient settings were included. Patients under 16 years of age and patients treated without FMT were excluded. Frozen stool from a standardized stool bank (OpenBiome) was used. The thawed specimen was instilled into the terminal ileum or the cecum. Patients were followed up for the next 1 year for analysis of improvement in symptoms, recurrence, and repeat FMT.<br><br>RESULTS: On the 2-months follow-up, 75% of patients reported symptomatic improvement, 15.6% reported no improvement while 9.4% did not follow up. Twenty-six (40.6%) patients had CDI recurrence in the following year; and 69.2% of patients with recurrence underwent a repeat FMT. There was no statistically significant correlation between CDI recurrence and the age (P value = 0.68), gender (P value = 0.61), previous use of proton pump inhibitors (PPIs, P value = 0.11) or antibiotics (P value = 0.45). There was a statistically significant correlation noted with the use of immunosuppressants and recurrence (P value = 0.04).<br><br>CONCLUSIONS: FMT is a successful treatment modality for refractory and recurrent CDI. Repeat treatments can be beneficial if there is a lack of initial response. Being immunosuppressed with medications is associated with the risk of recurrence.}, }
@article {pmid34525908, year = {2022}, author = {Zanza, C and Romenskaya, T and Thangathurai, D and Ojetti, V and Saviano, A and Abenavoli, L and Robba, C and Cammarota, G and Franceschi, F and Piccioni, A and Longhitano, Y}, title = {Microbiome in Critical Care: An Unconventional and Unknown Ally.}, journal = {Current medicinal chemistry}, volume = {29}, number = {18}, pages = {3179-3188}, doi = {10.2174/0929867328666210915115056}, pmid = {34525908}, issn = {1875-533X}, mesh = {COVID-19 ; *Critical Care ; Critical Illness ; Dysbiosis ; Humans ; *Microbiota ; }, abstract = {BACKGROUND: The digestive tract represents an interface between the external environment and the body where the interaction of a complex polymicrobial ecology has an important influence on health and disease. The physiological mechanisms that are altered during hospitalization and in the intensive care unit (ICU) contribute to the pathobiota's growth. Intestinal dysbiosis occurs within hours of being admitted to ICU. This may be due to different factors, such as alterations of normal intestinal transit, administration of various medications, or alterations in the intestinal wall, which causes a cascade of events that will lead to the increase of nitrates and decrease of oxygen concentration, and the liberation of free radicals.<br><br>OBJECTIVE: This work aims to report the latest updates on the microbiota's contribution to developing sepsis in patients in the ICU department. In this short review, the latest scientific findings on the mechanisms of intestinal immune defenses performed both locally and systemically have been reviewed. Additionally, we considered it necessary to review the literature on the basis of the many studies carried out on the microbiota in the critically ill as a prevention to the spread of the infection in these patients.<br><br>MATERIALS AND METHODS: This review has been written to answer four main questions: 1- What are the main intestinal flora's defense mechanisms that help us to prevent the risk of developing systemic diseases? 2- What are the main Systemic Abnormalities of Dysbiosis? 3- What are the Modern Strategies Used in ICU to Prevent the Infection Spreading? 4- What is the Relationship between COVID-19 and Microbiota? We reviewed 72 articles using the combination of following keywords: "microbiota" and "microbiota" and "intensive care", "intensive care" and "gut", "critical illness", "microbiota" and "critical care", "microbiota" and "sepsis", "microbiota" and "infection", and "gastrointestinal immunity" in: Cochrane Controlled Trials Register, Cochrane Library, Medline and Pubmed, Google Scholar, Ovid/Wiley. Moreover, we also consulted the site ClinicalTrials.com to find out studies that have been recently conducted or are currently ongoing.<br><br>RESULTS: The critical illness can alter intestinal bacterial flora leading to homeostasis disequilibrium. Despite numerous mechanisms, such as epithelial cells with calciform cells that together build a mechanical barrier for pathogenic bacteria, the presence of mucous associated lymphoid tissue (MALT) which stimulates an immune response through the production of interferon-gamma (IFN-y) and THN-a or or from the production of anti-inflammatory cytokines produced by lymphocytes Thelper 2. But these defenses can be altered following hospitalization in ICU and lead to serious complications, such as acute respiratory distress syndrome (ARDS), health care associated pneumonia (HAP) and ventilator associated pneumonia (VAP), systemic infection and multiple organ failure (MOF), but also to the development of coronary artery disease (CAD). In addition, the microbiota has a significant impact on the development of intestinal complications and the severity of the SARS-COVID-19 patients.<br><br>CONCLUSION: The microbiota is recognized as one of the important factors that can worsen the clinical conditions of patients who are already very frail in the intensive care unit. At the same time, the microbiota also plays a crucial role in the prevention of ICU-associated complications. By using the resources that are available, such as probiotics, synbiotics or fecal microbiota transplantation (FMT), we can preserve the integrity of the microbiota and the GUT, which will later help maintain homeostasis in ICU patients.}, }
@article {pmid34523250, year = {2021}, author = {Liu, C and Cheung, WH and Li, J and Chow, SK and Yu, J and Wong, SH and Ip, M and Sung, JJY and Wong, RMY}, title = {Understanding the gut microbiota and sarcopenia: a systematic review.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {12}, number = {6}, pages = {1393-1407}, pmid = {34523250}, issn = {2190-6009}, mesh = {Aged ; Animals ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Prebiotics ; *Sarcopenia/etiology/therapy ; *Synbiotics ; }, abstract = {BACKGROUND: Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut-muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia.<br><br>METHODS: A systematic review was performed in PubMed, Embase, Web of Science, and The Cochrane Library databases using the keywords (microbiota* OR microbiome*) AND (sarcopen* OR muscle). Studies reporting the alterations of gut microbiota and muscle/physical performance were analysed.<br><br>RESULTS: A total of 26 pre-clinical and 10 clinical studies were included. For animal studies, three revealed age-related changes and relationships between gut microbiota and muscle. Three studies focused on muscle characteristics of germ-free mice. Seventy-five per cent of eight faecal microbiota transplantation studies showed that the recipient mice successfully replicated the muscle phenotype of donors. There were positive effects on muscle from seven probiotics, two prebiotics, and short-chain fatty acids (SCFAs). Ten studies investigated on other dietary supplements, antibiotics, exercise, and food withdrawal that affected both muscle and gut microbiota. Twelve studies explored the potential mechanisms of the gut-muscle axis. For clinical studies, 6 studies recruited 676 elderly people (72.8&#xa0;&#xb1;&#xa0;5.6&#xa0;years, 57.8% female), while 4 studies focused on 244 young adults (29.7&#xa0;&#xb1;&#xa0;7.8&#xa0;years, 55.4% female). The associations of gut microbiota and muscle had been shown in four observational studies. Probiotics, prebiotics, synbiotics, fermented milk, caloric restriction, and exercise in six studies displayed inconsistent effects on muscle mass, function, and gut microbiota.<br><br>CONCLUSIONS: Altering the gut microbiota through bacteria depletion, faecal transplantation, and various supplements was shown to directly affect muscle phenotypes. Probiotics, prebiotics, SCFAs, and bacterial products are potential novel therapies to enhance muscle mass and physical performance. Lactobacillus and Bifidobacterium strains restored age-related muscle loss. Potential mechanisms of microbiome modulating muscle mainly include protein, energy, lipid, and glucose metabolism, inflammation level, neuromuscular junction, and mitochondrial function. The role of the gut microbiota in the development of muscle loss during aging is a crucial area that requires further studies for translation to patients.}, }
@article {pmid34521450, year = {2021}, author = {Wang, M and Zhu, Z and Lin, X and Li, H and Wen, C and Bao, J and He, Z}, title = {Gut microbiota mediated the therapeutic efficacies and the side effects of prednisone in the treatment of MRL/lpr mice.}, journal = {Arthritis research &amp; therapy}, volume = {23}, number = {1}, pages = {240}, pmid = {34521450}, issn = {1478-6362}, mesh = {Animals ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Glucocorticoids ; *Lupus Erythematosus, Systemic/drug therapy ; Mice ; Mice, Inbred MRL lpr ; Prednisone ; }, abstract = {BACKGROUND: Growing evidences indicate that the alterations in gut microbiota are associated with the efficacy of glucocorticoids (GCs) in the treatment of systemic lupus erythematosus (SLE). However, there is no evidence to prove whether gut microbiota directly mediates the effects of GCs.<br><br>METHODS: Using the MRL/lpr mice, this study firstly addressed the effects of three doses of prednisone on gut microbiota. Then, this study used fecal microbiota transplantation (FMT) to transfer the gut microbiota of prednisone-treated MRL/lpr mice into the blank MRL/lpr mice to reveal whether the gut microbiota regulated by prednisone had similar therapeutic efficiency and side effects as prednisone.<br><br>RESULTS: The effects of prednisone on gut microbiota were dose-dependent in the treatment of MRL/lpr mice. After transplantation into MRL/lpr mice, prednisone-regulated gut microbiota could alleviate lupus, which might be due to decreasing Ruminococcus and Alistipes and retaining the abundance of Lactobacillus. However, prednisone-regulated gut microbiota did not exhibit side effects as prednisone. The reason might be that the pathogens upregulated by prednisone could not survive in the MRL/lpr mice as exogenous microbiota, such as Parasutterella, Parabacteroides, and Escherichia-Shigella.<br><br>CONCLUSIONS: These data demonstrated that the transplantation of gut microbiota may be an effective method to obtain the therapeutic effects of GCs and avoid the side effects of GCs.}, }
@article {pmid34520306, year = {2022}, author = {Lee, S and Kalugotla, G and Ingle, H and Rodgers, R and Wu, C and Wang, Y and Li, Y and Yang, X and Zhang, J and Borella, NR and Deng, H and Droit, L and Hill, R and Peterson, ST and Desai, C and Lawrence, D and Lu, Q and Baldridge, MT}, title = {Intestinal antiviral signaling is controlled by autophagy gene Epg5 independent of the microbiota.}, journal = {Autophagy}, volume = {18}, number = {5}, pages = {1062-1077}, pmid = {34520306}, issn = {1554-8635}, support = {R01 AI141478/AI/NIAID NIH HHS/United States ; K99 AI141683/AI/NIAID NIH HHS/United States ; R01 AI139314/AI/NIAID NIH HHS/United States ; R01 AI127552/AI/NIAID NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; T32 HG000045/HG/NHGRI NIH HHS/United States ; R00 AI141683/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antiviral Restriction Factors ; Autophagy/genetics ; *Autophagy-Related Proteins/genetics ; *Intestines/immunology/pathology ; Mice ; *Microbiota ; Receptors, Interferon/genetics/metabolism ; Tumor Necrosis Factor-alpha ; *Vesicular Transport Proteins/genetics ; }, abstract = {Mutations in the macroautophagy/autophagy gene EPG5 are responsible for Vici syndrome, a human genetic disease characterized by combined immunodeficiency. Previously, we found that epg5[-/-] mice exhibit hyperinflammation in the lungs mediated by IL1B/IL-1β and TNF/TNFα, resulting in resistance to influenza. Here, we find that disruption of Epg5 results in protection against multiple enteric viruses including norovirus and rotavirus. Gene expression analysis reveals IFNL/IFN-λ responsive genes as a key alteration. Further, mice lacking Epg5 exhibit substantial alterations of the intestinal microbiota. Surprisingly, germ-free mouse studies indicate Epg5-associated inflammation of both the intestine and lung is microbiota-independent. Genetic studies support IFNL signaling as the primary mediator of resistance to enteric viruses, but not of microbial dysbiosis, in epg5[-/-] mice. This study unveils an important role, unexpectedly independent of the microbiota, for autophagy gene Epg5 in host organism protection by modulating intestinal IFNL responses.Abbreviations: CTNNB1: catenin (cadherin associated protein), beta 1; DAPI: 4',6-diamidino-2-phenylindole; EPG5: ectopic P-granules autophagy protein 5 homolog (C. elegans); FT: fecal transplant; IFI44: interferon-induced protein 44; IFIT1: interferon-induced protein with tetratricopeptide repeats 1; IFNG/IFN-γ: interferon gamma; IFNL/IFN-λ: interferon lambda; IFNLR1: interferon lambda receptor 1; IL1B/IL-1β: interleukin 1 beta; ISG: interferon stimulated gene; GF: germ-free; LEfSe: linear discriminant analysis effect size; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MNoV: murine norovirus; MX2: MX dynamin-like GTPase 2; OAS1A: 2'-5' oligoadenylate synthetase 1A; RV: rotavirus; SPF: specific-pathogen free; SQSTM1/p62: sequestosome 1; STAT1: signal transducer and activator of transcription 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK-binding kinase 1; TNF/TNFα: tumor necrosis factor.}, }
@article {pmid34519701, year = {2021}, author = {Mogilevski, T}, title = {The bi-directional role of the gut-brain axis in inflammatory and other gastrointestinal diseases.}, journal = {Current opinion in gastroenterology}, volume = {37}, number = {6}, pages = {572-577}, doi = {10.1097/MOG.0000000000000779}, pmid = {34519701}, issn = {1531-7056}, mesh = {Brain ; *Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {PURPOSE OF REVIEW: There is a growing body of evidence implicating the role of the gut-brain axis in a multitude of inflammatory and non-inflammatory gastrointestinal disorders. The interaction between the gut and the brain is bidirectional and its therapeutic manipulation is gaining traction as the new frontier in the management of gastrointestinal disorders. This review summarizes the recent literature on this subject and serves as a reference for future research directions.<br><br>RECENT FINDINGS: Recent studies have shown that the gut-brain axis, through its main communicator - the vagal nerve - plays a multimodal role in manipulating gastrointestinal physiology. This is evident systemically via the cholinergic anti-inflammatory pathway, through its effect on intestinal barrier function and also locally on intestinal epithelial and immune cells. Vagal nerve stimulation and faecal microbiota transplantation are two ways by which therapeutic manipulation has been attempted with success.<br><br>SUMMARY: There has been exceptional progress in our understanding of the gut-brain axis in recent literature. Its role in the modulation of a multitude of gastrointestinal disorders is becoming clear. Preclinical findings are sufficient for this research to proceed to clinical trials in order to harness its clinical therapeutic potential for the care of patients.}, }
@article {pmid34516769, year = {2021}, author = {Rizvi, ZA and Dalal, R and Sadhu, S and Kumar, Y and Kumar, S and Gupta, SK and Tripathy, MR and Rathore, DK and Awasthi, A}, title = {High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity.}, journal = {Science advances}, volume = {7}, number = {37}, pages = {eabg5016}, pmid = {34516769}, issn = {2375-2548}, abstract = {High-salt diet (HSD) modulates effector and regulatory T cell functions and promotes tissue inflammation in autoimmune diseases. However, effects of HSD and its association with gut microbiota in tumor immunity remain undefined. Here, we report that HSD induces natural killer (NK) cell–mediated tumor immunity by inhibiting PD-1 expression while enhancing IFNγ and serum hippurate. Salt enhanced tumor immunity when combined with a suboptimal dose of anti-PD1 antibody. While HSD-induced tumor immunity was blunted upon gut microbiota depletion, fecal microbiota transplantation (FMT) from HSD mice restored the tumor immunity associated with NK cell functions. HSD increased the abundance of Bifidobacterium and caused increased gut permeability leading to intratumor localization of Bifidobacterium, which enhanced NK cell functions and tumor regression. Intratumoral injections of Bifidobacterium activated NK cells, which inhibited tumor growth. These results indicate that HSD modulates gut microbiome that induces NK cell–dependent tumor immunity with a potential translational perspective.}, }
@article {pmid34516460, year = {2022}, author = {Singh, T and Bedi, P and Bumrah, K and Gandhi, D and Arora, T and Verma, N and Schleicher, M and Rai, MP and Garg, R and Verma, B and Sanaka, MR}, title = {Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection : Meta-analysis of Randomized Controlled Trials.}, journal = {Journal of clinical gastroenterology}, volume = {56}, number = {10}, pages = {881-888}, doi = {10.1097/MCG.0000000000001610}, pmid = {34516460}, issn = {1539-2031}, mesh = {Anti-Bacterial Agents ; *Clostridioides difficile ; *Clostridium Infections/therapy ; *Enterocolitis, Pseudomembranous/therapy ; Fecal Microbiota Transplantation/methods ; Humans ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome ; }, abstract = {GOALS: The aim was to assess the effectiveness of fecal microbiota transplantation (FMT) against medical therapy (MT).<br><br>BACKGROUND: FMT has shown good outcomes in the treatment of Clostridium difficile infection (CDI). We aimed to conduct a systematic review and meta-analysis to compare the effectiveness of FMT versus MT for CDI.<br><br>STUDY: We performed a comprehensive search to identify randomized controlled trials comparing FMT against MT in patients with CDI. Outcomes of interest were clinical cure as determined by the resolution of diarrhea and/or negative C. difficile testing. Primary CDI is defined as the first episode of CDI confirmed endoscopically or by laboratory analysis. Recurrent C. difficile infection (RCDI) is defined as laboratory or endoscopically confirmed episode of CDI after at least 1 course of approved antibiotic regimen.<br><br>RESULTS: A total of 7 studies with 238 patients were included in meta-analysis. Compared with MT, FMT did not have a statistically significant difference for clinical cure of combined primary and RCDI after first session [risk ratio (RR): 1.52, 95% confidence interval (CI): 0.90, 2.58; P =0.12; I2 =77%] and multiple sessions of FMT (RR: 1.68; CI: 0.96, 2.94; P =0.07; I2 =82%). On subgroup analysis, FMT has statistically higher rate of response than MT (RR: 2.41; CI: 1.20, 4.83; I2 =78%) for RCDI. However, for primary CDI there is no statistically significant difference between FMT and MT (RR: 1.00; CI: 0.72, 1.39; I2 =0%).<br><br>CONCLUSION: As per our analysis, FMT should not be utilized for every patient with CDI. It is more effective in RCDI, but the results were not significant in patients with primary CDI.}, }
@article {pmid34514619, year = {2022}, author = {Suchodolski, JS}, title = {Analysis of the gut microbiome in dogs and cats.}, journal = {Veterinary clinical pathology}, volume = {50 Suppl 1}, number = {Suppl 1}, pages = {6-17}, pmid = {34514619}, issn = {1939-165X}, mesh = {Animals ; *Cat Diseases ; Cats ; *Dog Diseases ; Dogs ; Dysbiosis/veterinary ; Feces ; *Gastrointestinal Microbiome ; }, abstract = {The gut microbiome is an important immune and metabolic organ. Intestinal bacteria produce various metabolites that influence the health of the intestine and other organ systems, including kidney, brain, and heart. Changes in the microbiome in diseased states are termed dysbiosis. The concept of dysbiosis is constantly evolving and includes changes in microbiome diversity and/or structure and functional changes (eg, altered production of bacterial metabolites). Molecular tools are now the standard for microbiome analysis. Sequencing of microbial genes provides information about the bacteria present and their functional potential but lacks standardization and analytical validation of methods and consistency in the reporting of results. This makes it difficult to compare results across studies or for individual clinical patients. The Dysbiosis Index (DI) is a validated quantitative PCR assay for canine fecal samples that measures the abundance of seven important bacterial taxa and summarizes the results as one single number. Reference intervals are established for dogs, and the DI can be used to assess the microbiome in clinical patients over time and in response to therapy (eg, fecal microbiota transplantation). In situ hybridization or immunohistochemistry allows the identification of mucosa-adherent and intracellular bacteria in animals with intestinal disease, especially granulomatous colitis. Future directions include the measurement of bacterial metabolites in feces or serum as markers for the appropriate function of the microbiome. This article summarizes different approaches to the analysis of gut microbiota and how they might be applicable to research studies and clinical practice in dogs and cats.}, }
@article {pmid34514495, year = {2022}, author = {Sarbagili Shabat, C and Scaldaferri, F and Zittan, E and Hirsch, A and Mentella, MC and Musca, T and Cohen, NA and Ron, Y and Fliss Isakov, N and Pfeffer, J and Yaakov, M and Fanali, C and Turchini, L and Masucci, L and Quaranta, G and Kolonimos, N and Godneva, A and Weinberger, A and Kopylov, U and Levine, A and Maharshak, N}, title = {Use of Faecal Transplantation with a Novel Diet for Mild to Moderate Active Ulcerative Colitis: The CRAFT UC Randomised Controlled Trial.}, journal = {Journal of Crohn's &amp; colitis}, volume = {16}, number = {3}, pages = {369-378}, pmid = {34514495}, issn = {1876-4479}, support = {//Azrieli Foundation/ ; }, mesh = {Adult ; *Colitis, Ulcerative/drug therapy/surgery ; Colonoscopy ; Diet ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Remission Induction ; }, abstract = {BACKGROUND: We evaluated whether integration of novel diets for donors and patients, in addition to faecal transplantation [FT], could increase FT remission rate in refractory ulcerative colitis [UC].<br><br>METHODS: This was a blinded, randomised, controlled trial in adults with active UC, defined by a simple clinical colitis activity index [SCCAI] of&#x2005;&#x2265;5 and&#x2005;&#x2264;11 and endoscopic Mayo score 2-3, refractory to medication. Group 1 received free diet and single donor standard FT by colonoscopy on Day 1and rectal enemas on Days 2 and 14 without dietary conditioning of the donor. Group 2 received FT as above but with dietary pre-conditioning of the donor for 14 days and a UC Exclusion Diet [UCED] for the patients. Group 3 received the UCED alone. The primary endpoint was Week 8 clinical steroid-free remission, defined as SCCAI&#x2005;<3.<br><br>RESULTS: Of 96 planned patients, 62 were enrolled. Remission Week 8 Group 1 was 2/17 [11.8%], Group 2 was 4/19 [21.1%], Group 3 was 6/15 [40%] [non-significant]. Endoscopic remission Group 1 was 2/17 [12%], Group 2 was 3/19 [16%], Group 3 was 4/15 [27%] [Group 1 vs 3 p&#x2005;=&#x2005;0.38]. Mucosal healing [Mayo 0] was achieved only in Group 3 [3/15, 20%] vs 0/36 FT patients [p&#x2005;=&#x2005;0.022]. Exacerbation of disease occurred in 3/17 [17.6%] of Group 1, 4/19 [21.1%] of Group 2, and 1/15 [6.7%] of Group 3 [Group 2 vs 3, p&#x2005;=&#x2005;0.35].<br><br>CONCLUSIONS: UCED alone appeared to achieve higher clinical remission and mucosal healing than single donor FT with or without diet. The study was stopped for futility by a safety monitoring board.}, }
@article {pmid34513724, year = {2021}, author = {Innes, AJ and Mullish, BH and Ghani, R and Szydlo, RM and Apperley, JF and Olavarria, E and Palanicawandar, R and Kanfer, EJ and Milojkovic, D and McDonald, JAK and Brannigan, ET and Thursz, MR and Williams, HRT and Davies, FJ and Marchesi, JR and Pavlů, J}, title = {Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {684659}, pmid = {34513724}, issn = {2235-2988}, support = {MR/T005254/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; /DH_/Department of Health/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Humans ; Retrospective Studies ; }, abstract = {The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2% respectively, p=0.24) between the FMT-MDRO group and their paired non-MDRO cohort. Collectively, these data suggest that negative clinical outcomes, including mortality associated with MDRO colonization, may be ameliorated by pre-HCT FMT, even in the absence of intestinal MDRO decolonization. Further work is needed to explore this observed benefit.}, }
@article {pmid34512631, year = {2021}, author = {Bozward, AG and Ronca, V and Osei-Bordom, D and Oo, YH}, title = {Gut-Liver Immune Traffic: Deciphering Immune-Pathogenesis to Underpin Translational Therapy.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {711217}, pmid = {34512631}, issn = {1664-3224}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Antibodies, Monoclonal, Humanized/therapeutic use ; Bile Acids and Salts/physiology ; Cholangitis, Sclerosing/drug therapy/*etiology/immunology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Inflammatory Bowel Diseases/etiology ; Intestinal Mucosa/*immunology ; Liver/*immunology ; Liver Cirrhosis, Biliary/etiology ; Receptors, Cytoplasmic and Nuclear/physiology ; T-Lymphocytes, Regulatory/immunology ; Vancomycin/pharmacology ; }, abstract = {The tight relationship between the gut and liver on embryological, anatomical and physiological levels inspired the concept of a gut-liver axis as a central element in the pathogenesis of gut-liver axis diseases. This axis refers to the reciprocal regulation between these two organs causing an integrated system of immune homeostasis or tolerance breakdown guided by the microbiota, the diet, genetic background, and environmental factors. Continuous exposure of gut microbiome, various hormones, drugs and toxins, or metabolites from the diet through the portal vein adapt the liver to maintain its tolerogenic state. This is orchestrated by the combined effort of immune cells network: behaving as a sinusoidal and biliary firewall, along with a regulatory network of immune cells including, regulatory T cells and tolerogenic dendritic cells (DC). In addition, downregulation of costimulatory molecules on hepatic sinusoids, hepatocytes and biliary epithelial cells as well as regulating the bile acids chain also play a part in hepatic immune homeostasis. Recent evidence also demonstrated the link between changes in the gut microbiome and liver resident immune cells in the progression of cirrhosis and the tight correlation among primary sclerosing cholangitis (PSC) and also checkpoint induced liver and gut injury. In this review, we will summarize the most recent evidence of the bidirectional relationship among the gut and the liver and how it contributes to liver disease, focusing mainly on PSC and checkpoint induced hepatitis and colitis. We will also focus on completed therapeutic options and on potential targets for future treatment linking with immunology and describe the future direction of this research, taking advantage of modern technologies.}, }
@article {pmid34509994, year = {2021}, author = {Houf, J}, title = {Faecal microbiota transplants: towards a healthy disgust scepticism.}, journal = {Medical humanities}, volume = {47}, number = {4}, pages = {407-416}, doi = {10.1136/medhum-2020-012135}, pmid = {34509994}, issn = {1473-4265}, mesh = {*Disgust ; Emotions ; Humans ; *Microbiota ; Morals ; }, abstract = {This paper engages with the obstacle of disgust surrounding the use of faecal microbiota transplants (FMT). In discourse about the human microbiome and microbiota-based therapies (like FMT), disgust has become an unavoidable emotion for physicians, patients and caregivers interested in these therapies. Additionally, microbiota therapies and microbiomes are challenging our conception of an individual biological self. As these two discourses converge with FMT, it becomes necessary to understand how they are working together. To do this, this paper explores the way disgust functions in the formation of subjects. Scholarship about disgust can be categorised into two approaches: disgust as a deep wisdom or disgust scepticism. The former approach focuses on the physiological, embodied aspects of our disgust reactions as evidence of 'truth' in disgusting encounters, and the latter recognises the way disgust is culturally contingent and adapted for use in moral and social determinations of good and bad. However, both positions accept the use of disgust as a defence against 'toxins and diseases'. Yet, as this paper argues, we should take the sceptical approach further. The disgust sceptical approach, particularly as developed by Sarah Ahmed, does more than just challenge disgust's role in moral deliberations. It also demands sceptical reflection on disgust as a universal defence against 'toxins and diseases'. Much as disgust can be co-opted to support oppression, it too can be co-opted to reconstitute a false vision of human subjectivity-the coherent, contained and exceptional human subject situated above the natural world. The human microbiome, faecal therapeutics and being disgusted give us an opportunity to recognise ourselves as more-than-human subjects.}, }
@article {pmid34508776, year = {2021}, author = {van de Guchte, M and Mondot, S and Doré, J}, title = {Dynamic Properties of the Intestinal Ecosystem Call for Combination Therapies, Targeting Inflammation and Microbiota, in Ulcerative Colitis.}, journal = {Gastroenterology}, volume = {161}, number = {6}, pages = {1969-1981.e12}, doi = {10.1053/j.gastro.2021.08.057}, pmid = {34508776}, issn = {1528-0012}, mesh = {Anti-Inflammatory Agents/adverse effects/*therapeutic use ; Bacteria/*drug effects/genetics/immunology ; Case-Control Studies ; *Cellular Microenvironment ; Colitis, Ulcerative/immunology/microbiology/*therapy ; Combined Modality Therapy ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/*drug effects ; Inflammation Mediators/*antagonists &amp; inhibitors/metabolism ; Intestines/*drug effects/metabolism/microbiology ; Models, Biological ; Remission Induction ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Intestinal microbiota-host interactions play a major role in health and disease. This has been documented at the microbiota level ("dysbiosis" in chronic immune-mediated diseases) and through the study of specific bacteria-host interactions but rarely at the level of intestinal ecosystem dynamics. However, understanding the behavior of this ecosystem may be key to the successful treatment of disease. We recently postulated that health and disease represent alternative stable states of the intestinal ecosystem (different configurations that can exist under identical external conditions), which would require adapted strategies in disease treatment. Here, we examine if alternative stable states indeed exist in this ecosystem and if they could affect remission from ulcerative colitis (UC).<br><br>METHODS: We analyzed data from a study on pediatric UC. The data reflect current treatment practice following the recruitment of treatment-naive patients with new-onset disease. Patients received personalized anti-inflammatory treatments over a period of 1 year. Stool samples at 0, 4, 12, and 52 weeks allowed an estimation of microbiota status (through 16S ribosomal RNA gene sequencing) and host inflammatory status (through the measurement of fecal calprotectin levels).<br><br>RESULTS: We identify 4 microbiota states and 4 host states. Longitudinal data show that the improvement of inflammatory status is accompanied by an improvement of microbiota status. However, they also provide strong indications that both improvements are retarded or blocked by alternative states barriers.<br><br>CONCLUSIONS: Our observations strongly suggest that inflammation suppression should be combined with microbiota management where possible to improve the efficacy of UC treatment.}, }
@article {pmid34508775, year = {2022}, author = {Lau, HC and Ng, SC and Yu, J}, title = {Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?.}, journal = {Gastroenterology}, volume = {162}, number = {1}, pages = {9-16}, pmid = {34508775}, issn = {1528-0012}, mesh = {COVID-19/etiology/*microbiology/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Probiotics/therapeutic use ; *SARS-CoV-2 ; Severity of Illness Index ; }, }
@article {pmid34507723, year = {2021}, author = {Pang, B and Jin, H and Liao, N and Li, J and Jiang, C and Shi, J}, title = {Vitamin A supplementation ameliorates ulcerative colitis in gut microbiota-dependent manner.}, journal = {Food research international (Ottawa, Ont.)}, volume = {148}, number = {}, pages = {110568}, doi = {10.1016/j.foodres.2021.110568}, pmid = {34507723}, issn = {1873-7145}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy ; Dextran Sulfate ; Dietary Supplements ; Gas Chromatography-Mass Spectrometry ; *Gastrointestinal Microbiome ; Mice ; RNA, Ribosomal, 16S/genetics ; Vitamin A ; }, abstract = {Ulcerative colitis (UC), is a chronic relapsing inflammatory condition of the gastrointestinal track. The purpose of this study is to explore whether Vitamin A (VA) can treat UC and its mechanisms. A mouse model of UC was established using 3.0% (w/v) dextran sodium sulfate (DSS). VA was used to treat UC by intragastric administration of 5000 international unit (IU) retinyl acetate. Fecal microbiota transplantation (FMT) was also used to treat the UC model mice to verify the effect of influenced gut microbiota. The content of short-chain fatty acids (SCFAs) in cecal contents was quantitatively detected by gas chromatography and mass spectrometry. VA supplementation significantly ameliorated UC. 16S rRNA sequencing indicated that VA-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased production of SCFAs in VA-treated mice. Gut microbiota depletion and FMT results confirmed the gut microbiota-dependent mechanism as that VA relieved UC via regulating gut microbiota: increase in SCFA-producing genera and decrease in UC-related genera. The restore of intestinal barrier and the inhibition of inflammation were also found to contribute to the amelioration of UC by VA. It was concluded that a VA supplement was enough to cause a significant change in gut microbiota and amelioration of UC.}, }
@article {pmid34500036, year = {2021}, author = {Kim, N and Jeon, SH and Ju, IG and Gee, MS and Do, J and Oh, MS and Lee, JK}, title = {Transplantation of gut microbiota derived from Alzheimer's disease mouse model impairs memory function and neurogenesis in C57BL/6 mice.}, journal = {Brain, behavior, and immunity}, volume = {98}, number = {}, pages = {357-365}, doi = {10.1016/j.bbi.2021.09.002}, pmid = {34500036}, issn = {1090-2139}, mesh = {*Alzheimer Disease ; Animals ; *Gastrointestinal Microbiome ; Humans ; Mice ; Mice, Inbred C57BL ; *Neurodegenerative Diseases ; Neurogenesis ; }, abstract = {Alzheimer's disease (AD) is a neurodegenerative disease that causes memory and cognitive decline. Although many studies have attempted to clarify the causes of AD occurrence, it is not clearly understood. Recently, the emerging role of the gut microbiota in neurodegenerative diseases, including AD, has received much attention. The gut microbiota composition of AD patients and AD mouse models is different from that of healthy controls, and these changes may affect the brain environment. However, the specific mechanisms by which gut microbiota that influence memory decline are currently unclear. In this study, we performed fecal microbiota transplantation (FMT) to clarify the role of 5xFAD mouse-derived microbiota in memory decline. We observed that FMT from 5xFAD mice into normal C57BL/6 mice (5xFAD-FMT) decreased adult hippocampal neurogenesis and brain-derived neurotrophic factor expression and increased p21 expression, resulting in memory impairment. Microglia in the hippocampus of the 5xFAD-FMT mice were activated, which caused the elevation of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β). Moreover, we observed that pro-inflammatory cytokines increased in the colon and plasma of 5xFAD-FMT mice. The gut microbiota composition of the 5xFAD-FMT mice was different from that of the control mice or wild type-FMT mice. Collectively, 5xFAD mouse-derived microbiota decreased neurogenesis by increasing colonic inflammation, thereby contributing to memory loss. Our findings provide further evidence concerning the role of gut microbial dysbiosis in AD pathogenesis and suggest that targeting the gut microbiota may be a useful therapeutic strategy for the development of novel candidates for the treatment of AD.}, }
@article {pmid34495400, year = {2022}, author = {El Halabi, J and Palmer, N and Fox, K and Kohane, I and Farhat, MR}, title = {Fecal microbiota transplantation and Clostridioides difficile infection among privately insured patients in the United States.}, journal = {Journal of gastroenterology}, volume = {57}, number = {1}, pages = {10-18}, pmid = {34495400}, issn = {1435-5922}, support = {T15LM007092/NH/NIH HHS/United States ; K01 ES026835/NH/NIH HHS/United States ; }, mesh = {*Clostridioides difficile ; *Clostridium Infections/epidemiology/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; Female ; Humans ; Insurance, Health ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; United States/epidemiology ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) may be rising in severity in the US over the past decade and its treatment landscape is changing given the recent adoption of fecal microbiota transplantation (FMT) METHODS: We built a retrospective observational cohort using a database of a national care-plan containing medical claims of over 50 million individuals between 2008 and 2019. We used International Classification of Disease (ICD) and prescription data to identify patients with CDI. We estimated trends in disease burden and FMT use, and evaluated complications post FMT using a phenome-wide association approach.<br><br>RESULTS: We identified 38,396 patients with CDI; the median age was 60&#xa0;years (IQR 45-74) and 60% were female (n&#x2009;=&#x2009;23,374). The rate of CDI increased from 33.4 to 69.46 cases per 100,000 person-years between 2008 and 2015, and stabilized from 2015 to 2019 (increase of 4.77 cases per 100,000 person-years per year, 95% CI 3.55-5.98 prior to 2015 vs. 2.01 95% CI - 10.16 to 14.18 after 2015). Of the 7715 patients with recurrent CDI, 407 patients (5%) underwent FMT. Gastrointestinal complications were increased within 1 month post FMT (OR 99.60, p&#x2009;<&#x2009;0.001). Sepsis was identified in two individuals (0.49% 95% CI 0.05-1.7%) within the first month post FMT. The risk of CDI recurrence significantly decreased post FMT compared with anti-CDI antibiotics in the multivariable model (raw-recurrence rate 9.8% vs 36%, aOR&#x2009;=&#x2009;0.21, 95% CI 0.12-0.53, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: We show that FMT is strongly associated with a decrease in CDI recurrence compared with the usual care with generally mild complications for up to 2&#xa0;years.}, }
@article {pmid34494666, year = {2022}, author = {Mjaess, G and Karam, A and Aoun, F and Albisinni, S and Roumeguère, T}, title = {Fecal microbiota transplantation for immunotherapy-resistant urological tumors: Is it time? An update of the recent literature.}, journal = {Cancer}, volume = {128}, number = {1}, pages = {14-19}, doi = {10.1002/cncr.33893}, pmid = {34494666}, issn = {1097-0142}, mesh = {*Carcinoma, Renal Cell ; Fecal Microbiota Transplantation ; Humans ; Immunotherapy ; *Kidney Neoplasms ; *Urologic Neoplasms/therapy ; }, }
@article {pmid34494661, year = {2022}, author = {Narayan, VM}, title = {Altering the microbiome for immunotherapy-resistant urological tumors-An intriguing but still early concept.}, journal = {Cancer}, volume = {128}, number = {1}, pages = {20-21}, doi = {10.1002/cncr.33891}, pmid = {34494661}, issn = {1097-0142}, mesh = {Humans ; Immunotherapy ; *Microbiota ; *Urologic Neoplasms/therapy ; }, }
@article {pmid34493333, year = {2021}, author = {Wu, Z and Huang, S and Li, T and Li, N and Han, D and Zhang, B and Xu, ZZ and Zhang, S and Pang, J and Wang, S and Zhang, G and Zhao, J and Wang, J}, title = {Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {184}, pmid = {34493333}, issn = {2049-2618}, mesh = {Animals ; *Colitis/chemically induced/drug therapy ; Dextran Sulfate ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Homeostasis ; Mice ; Mice, Inbred C57BL ; Polyphenols/pharmacology ; Tea ; }, abstract = {BACKGROUND: Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD.<br><br>RESULTS: We first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT.<br><br>CONCLUSIONS: This study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD. Video Abstract.}, }
@article {pmid34490132, year = {2021}, author = {Jia, X and Xu, W and Zhang, L and Li, X and Wang, R and Wu, S}, title = {Impact of Gut Microbiota and Microbiota-Related Metabolites on Hyperlipidemia.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {634780}, pmid = {34490132}, issn = {2235-2988}, mesh = {Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Hyperlipidemias ; *Metabolic Diseases ; Mice ; *Microbiota ; }, abstract = {Hyperlipidemia, defined as the presence of excess fat or lipids in the blood, has been considered as a high-risk factor and key indicator of many metabolic diseases. The gut microbiota has been reported playing a vital role in regulating host lipid metabolism. The pathogenic role of gut microbiota in the development of hyperlipidemia has been revealed through fecal microbiota transplantation experiment to germ-free mice. The effector mechanism of microbiota-related metabolites such as bile acids, lipopolysaccharide, and short-chain fatty acids in the regulation of hyperlipidemia has been partially unveiled. Moreover, studies on gut-microbiota-targeted hyperlipidemia interventions, including the use of prebiotics, probiotics, fecal microbiota transplantation, and natural herbal medicines, also have shown their efficacy in the treatment of hyperlipidemia. In this review, we summarize the relationship between gut microbiota and hyperlipidemia, the impact of gut microbiota and microbiota-related metabolites on the development and progression of hyperlipidemia, and the potential therapeutic management of hyperlipidemia targeted at gut microbiota.}, }
@article {pmid34490119, year = {2021}, author = {Liu, X and Cheng, Y and Zang, D and Zhang, M and Li, X and Liu, D and Gao, B and Zhou, H and Sun, J and Han, X and Lin, M and Chen, J}, title = {The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {720842}, pmid = {34490119}, issn = {2234-943X}, abstract = {The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.}, }
@article {pmid34489956, year = {2021}, author = {Roberto, M and Carconi, C and Cerreti, M and Schipilliti, FM and Botticelli, A and Mazzuca, F and Marchetti, P}, title = {The Challenge of ICIs Resistance in Solid Tumours: Could Microbiota and Its Diversity Be Our Secret Weapon?.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {704942}, pmid = {34489956}, issn = {1664-3224}, mesh = {Drug Resistance, Neoplasm/*immunology ; *Gastrointestinal Microbiome/drug effects/immunology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; *Immunotherapy ; *Neoplasms/drug therapy/immunology/microbiology ; }, abstract = {The human microbiota and its functional interaction with the human body were recently returned to the spotlight of the scientific community. In light of the extensive implementation of newer and increasingly precise genome sequencing technologies, bioinformatics, and culturomic, we now have an extraordinary ability to study the microorganisms that live within the human body. Most of the recent studies only focused on the interaction between the intestinal microbiota and one other factor. Considering the complexity of gut microbiota and its role in the pathogenesis of numerous cancers, our aim was to investigate how microbiota is affected by intestinal microenvironment and how microenvironment alterations may influence the response to immune checkpoint inhibitors (ICIs). In this context, we show how diet is emerging as a fundamental determinant of microbiota's community structure and function. Particularly, we describe the role of certain dietary factors, as well as the use of probiotics, prebiotics, postbiotics, and antibiotics in modifying the human microbiota. The modulation of gut microbiota may be a secret weapon to potentiate the efficacy of immunotherapies. In addition, this review sheds new light on the possibility of administering fecal microbiota transplantation to modulate the gut microbiota in cancer treatment. These concepts and how these findings can be translated into the therapeutic response to cancer immunotherapies will be presented.}, }
@article {pmid34488633, year = {2021}, author = {Li, T and Garcia-Gutierrez, E and Yara, DA and Scadden, J and Davies, J and Hutchins, C and Aydin, A and O'Grady, J and Narbad, A and Romano, S and Sayavedra, L}, title = {An optimised protocol for detection of SARS-CoV-2 in stool.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {242}, pmid = {34488633}, issn = {1471-2180}, support = {BB/S506679/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10352/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M011216/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10351/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10355/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10348/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012504/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10349/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/OS/NW/000006/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*COVID-19/diagnosis/virology ; COVID-19 Nucleic Acid Testing/*methods ; Feces/*virology ; Humans ; Limit of Detection ; RNA, Viral/*isolation &amp; purification ; SARS-CoV-2/*isolation &amp; purification ; }, abstract = {BACKGROUND: SARS-CoV-2 has been detected in stool samples of COVID-19 patients, with potential implications for faecal-oral transmission. Compared to nasopharyngeal swab samples, the complexity of the stool matrix poses a challenge in the detection of the virus that has not yet been solved. However, robust and reliable methods are needed to estimate the prevalence and persistence of SARS-CoV-2 in the gut and to ensure the safety of microbiome-based procedures such as faecal microbiota transplant (FMT). The aim of this study was to establish a sensitive and reliable method for detecting SARS-CoV-2 in stool samples.<br><br>RESULTS: Stool samples from individuals free of SARS-CoV-2 were homogenised in saline buffer and spiked with a known titre of inactivated virus ranging from 50 to 750 viral particles per 100&#xa0;mg stool. Viral particles were concentrated by ultrafiltration, RNA was extracted, and SARS-CoV-2 was detected via real-time reverse-transcription polymerase chain reaction (RT-qPCR) using the CDC primers and probes. The RNA extraction procedure we used allowed for&#xa0;the detection of SARS-CoV-2 via RT-qPCR in most of the stool samples tested. We could detect as few as 50 viral particles per 100&#xa0;mg of stool. However, high variability was observed across samples at low viral titres. The primer set targeting the N1 region provided more reliable and precise results and for this primer set our method had a limit of detection of 1 viral particle per mg of stool.<br><br>CONCLUSIONS: Here we describe a sensitive method for detecting SARS-CoV-2 in stool samples. This method can be used to establish the persistence of SARS-CoV-2 in stool and ensure the safety of clinical practices such as FMT.}, }
@article {pmid34487914, year = {2022}, author = {Opoku-Acheampong, I and McLaud, T and Anderson, OS}, title = {Fecal Microbiota Transplantation to Prevent and Treat Chronic Disease: Implications for Dietetics Practice.}, journal = {Journal of the Academy of Nutrition and Dietetics}, volume = {122}, number = {1}, pages = {33-37}, doi = {10.1016/j.jand.2021.08.112}, pmid = {34487914}, issn = {2212-2672}, mesh = {Chronic Disease/*therapy ; Dietetics ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Public Health ; Role ; }, }
@article {pmid34487562, year = {2021}, author = {Lengliz, S and Benlabidi, S and Raddaoui, A and Cheriet, S and Ben Chehida, N and Najar, T and Abbassi, MS}, title = {High occurrence of carbapenem-resistant Escherichia coli isolates from healthy rabbits (Oryctolagus cuniculus): first report of blaIMI and blaVIM type genes from livestock in Tunisia.}, journal = {Letters in applied microbiology}, volume = {73}, number = {6}, pages = {708-717}, doi = {10.1111/lam.13558}, pmid = {34487562}, issn = {1472-765X}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Carbapenems/pharmacology ; *Escherichia coli/genetics ; *Livestock ; Microbial Sensitivity Tests ; Rabbits ; Tunisia ; beta-Lactamases/genetics ; }, abstract = {We aimed to study the antibiotic susceptibility and possible occurrence of extended-spectrum beta-lactamases (ESBL)/carbapenemase-producing Escherichia coli isolates collected from rabbits in Tunisia. In all, 35 faecal samples from healthy rabbits were collected from one farm and E. coli were isolated from three media: antibiotic-free TBX agar, TBX+2 mg l[-1] cefotaxime and TBX+1 mg l[-1] imipenem. In total, 39 E. coli isolates were recovered; the majority showed resistance to at least one antibiotic and none was ESBL producer. Carbapenem resistance was detected in 16 isolates from either selective or un-selective media. Phenotypic methods used to detect carbapenemase production showed two positive isolates by Modified Hodge Test, six metallo-carbapenemase producers (Imipenem disc+EDTA) and all were temocillin resistant (possible OXA-48 carbapenemase). blaVIM and blaIMP type genes were detected in two and one isolates, respectively; one of them harboured both genes. Isolates contained common genes encoding resistance to sulphonamides (sul1, sul2), tetracycline (tetA, tetB, tetC) and fluoroquinolones (qnrS, aac(6')-Ib-cr). Class 1 and 2 integrons were detected in five and four isolates, respectively. These findings highlight the importance of rabbit production as reservoir of carbapenem-resistant E. coli and argument the first report of blaVIM and blaIMP genes in livestock in Tunisia.}, }
@article {pmid34486891, year = {2023}, author = {Sanlier, N and Kocabas, &#x15e;}, title = {The effect of probiotic, prebiotic and gut microbiota on ASD: A review and future perspectives.}, journal = {Critical reviews in food science and nutrition}, volume = {63}, number = {15}, pages = {2319-2330}, doi = {10.1080/10408398.2021.1973957}, pmid = {34486891}, issn = {1549-7852}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Prebiotics ; *Autism Spectrum Disorder ; *Probiotics ; *Microbiota ; }, abstract = {Autism spectrum disorder is a serious neurodevelopmental disease that affects social communication and behavior, characterized by an increasingly common immune mechanism and various complications in the gastrointestinal system. Symptoms of autism can generally vary according to the genetic background of the individuals, the environment in which they live. The microbiota of individuals with autism is also different from healthy individuals. Recently, probiotics, prebiotic, fecal microbiota transplantation, diet therapy, etc. options have come to the fore. Cofactors are even more important at this stage. Since it is related to the gut microbiota, immune mechanism, gastrointestinal system, attention has been drawn to the relationship between dysbiosis, autism in the intestine. The component of the gut microbiota in individuals with autism has been linked with gastrointestinal symptoms that develop with autism severity. However, the role of the microbiota in diagnosis, follow-up, treatment is not clear yet, and its two-way relationship with the nervous system makes it difficult to establish a cause-effect relationship. Nutritional cofactors required in neurotransmitter synthesis and enzyme activation must be regularly and adequately taken to maximize brain functions in autistic individuals. Therefore, this study was conducted to investigate the cause-effect relationship of ASD with microbiota and brain-gut axis, probiotic-prebiotic use.}, }
@article {pmid34484424, year = {2021}, author = {Cold, F and Baunwall, SMD and Dahlerup, JF and Petersen, AM and Hvas, CL and Hansen, LH}, title = {Systematic review with meta-analysis: encapsulated faecal microbiota transplantation - evidence for clinical efficacy.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211041004}, pmid = {34484424}, issn = {1756-283X}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infection (rCDI) and is being applied experimentally in other diseases. Encapsulated administration may be equivalent in efficacy to delivery through other routes.<br><br>METHODS: A systematic review was undertaken of studies using encapsulated FMT up to 26 October 2020. Data on indication, clinical outcomes, safety, treatment protocol and capsule preparation were collected and reported. Pooled rates of clinical efficacy in rCDI were calculated using random-effects meta-analysis. The impact of single variables on clinical efficacy was evaluated using univariate meta-regression.<br><br>RESULTS: A total of 35 studies reporting the treatment of 960 patients with encapsulated FMT for eight different indications met the inclusion criteria. Most studies (n&#x2009;=&#x2009;18, 51%) and patients (n&#x2009;=&#x2009;755, 79%) were from studies on rCDI. Cure rates after single and multiple courses of treatments with encapsulated FMT in rCDI were 85% (95% CI: 82%-88%) and 93% (95% CI: 88%-96%) respectively. The treatment outcome was not significantly affected by dose, number of delivered capsules, anaerobic/aerobic processing, single/multi-donor treatment, lyophilisation, or any other single factor in the production or delivery of encapsulated FMT. Promising but non-comparable results from the treatment of ulcerative colitis and multidrug-resistant organisms were reported.<br><br>CONCLUSIONS: Encapsulated FMT is an effective and safe treatment of rCDI, with cure rates comparable to FMT delivered through other routes. The treatment is effective despite variations in donor screening, preparation and treatment protocol. For other indications, the role of FMT capsules is still not sufficiently examined, although some studies show promising results.<br><br>PLAIN LANGUAGE SUMMARY: Transfer of faecal material through capsules in the treatment of various diseases. Evidence for clinical efficacy The bacteria and other microorganisms of the gut is different in patient with various diseases in comparison with healthy subjects.Therefore, ways to change the microorganisms of the gut in a beneficial direction has been the subject of various research projects within recent years.Faecal microbiota transplantation often referred as FMT is a method of transferring microorganisms from healthy donors to patients with various diseases and is seen as one way to change the microbial community of the gut in a beneficial direction.Faecal microbiota transplantation can be performed in different ways such as through endoscopy, enemas or capsules. The transfer through capsules is preferred by the patients and has advantages since it can be administered long-term and can be delivered to the patients in their home. In this paper, we evaluated all accessible research reporting treatment with encapsulated faecal microbiota transplantation in the treatment of various diseases. We report the following major findings:-Treatment with capsules is safe when guidelines for screening donors and testing faecal material is followed.-The treatment is highly effective in the treatment of recurrent C. difficile infection, a disease with high mortality often caused by repeated antibiotic treatments. The treatment was effective in 596 of 723 patients following one course of capsule treatment.-Faecal microbiota transplantation delivered through capsules is as effective as treatment delivered through other routes in the treatment of C. difficile infection.-The treatment is effective in the treatment of C. difficile infection across studies and countries, despite great differences in the ways the capsules were prepared and delivered.-Increasing the amount of faecal material used in the production did not affect the efficacy of the treatment.-There are promising results in the treatment of other diseases such as liver disease, inflammatory bowel disease and the treatment of multi-drug resistant bacteria.}, }
@article {pmid34484158, year = {2021}, author = {Yang, Y and Li, X and Yang, Y and Shoaie, S and Zhang, C and Ji, B and Wei, Y}, title = {Advances in the Relationships Between Cow's Milk Protein Allergy and Gut Microbiota in Infants.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {716667}, pmid = {34484158}, issn = {1664-302X}, abstract = {Cow's milk protein allergy (CMPA) is an immune response to cow's milk proteins, which is one of the most common food allergies in infants and young children. It is estimated that 2-3% of infants and young children have CMPA. The diet, gut microbiota, and their interactions are believed to be involved in the alterations of mucosal immune tolerance, which might lead to the development of CMPA and other food allergies. In this review, the potential molecular mechanisms of CMPA, including omics technologies used for analyzing microbiota, impacts of early microbial exposures on CMPA development, and microbiota-host interactions, are summarized. The probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and other modulation strategies for gut microbiota and the potential application of microbiota-based design of diets for the CMPA treatment are also discussed. This review not only summarizes the current studies about the interactions of CMPA with gut microbiota but also gives insights into the possible CMPA treatment strategies by modulating gut microbiota, which might help in improving the life quality of CMPA patients in the future.}, }
@article {pmid34484126, year = {2021}, author = {Jo, S and Fang, S}, title = {Therapeutic Strategies for Diabetes: Immune Modulation in Pancreatic β Cells.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {716692}, pmid = {34484126}, issn = {1664-2392}, mesh = {Animals ; *Autoimmunity ; Diabetes Mellitus, Type 1/immunology/pathology/*therapy ; Diabetes Mellitus, Type 2/immunology/pathology/*therapy ; *Gastrointestinal Microbiome ; Humans ; *Immune System ; Insulin-Secreting Cells/*immunology ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Increased incidence of type I and type II diabetes has been prevailed worldwide. Though the pathogenesis of molecular mechanisms remains still unclear, there are solid evidence that disturbed immune homeostasis leads to pancreatic β cell failure. Currently, autoimmunity and uncontrolled inflammatory signaling pathways have been considered the major factors in the pathogenesis of diabetes. Many components of immune system have been reported to implicate pancreatic β cell failure, including helper T cells, cytotoxic T cells, regulatory T cells and gut microbiota. Immune modulation of those components using small molecules and antibodies, and fecal microbiota transplantation are undergoing in many clinical trials for the treatment of type I and type II diabetes. In this review we will discuss the basis of molecular pathogenesis focusing on the disturbed immune homeostasis in type I and type II diabetes, leading to pancreatic β cell destruction. Finally, we will introduce current therapeutic strategies and clinical trials by modulation of immune system for the treatment of type I and type II diabetes patients.}, }
@article {pmid34482269, year = {2021}, author = {Farshbafnadi, M and Agah, E and Rezaei, N}, title = {The second brain: The connection between gut microbiota composition and multiple sclerosis.}, journal = {Journal of neuroimmunology}, volume = {360}, number = {}, pages = {577700}, doi = {10.1016/j.jneuroim.2021.577700}, pmid = {34482269}, issn = {1872-8421}, mesh = {Animals ; *Brain-Gut Axis/immunology/physiology ; Disease Models, Animal ; Dysbiosis/*complications/physiopathology/therapy ; Encephalomyelitis, Autoimmune, Experimental/*microbiology/physiopathology ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred Strains ; Mice, Transgenic ; Multiple Sclerosis/etiology/*microbiology/physiopathology/therapy ; Neurodegenerative Diseases/etiology/immunology/microbiology ; Probiotics ; Rats ; Vitamin D/therapeutic use ; }, abstract = {Gut microbiota composition may affect the central nervous system (CNS) and immune function. Several studies have recently examined the possible link between gut microbiota composition and multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Most of these studies agree that patients with MS suffer from dysbiosis. Moreover, an altered proportion of certain phyla of bacteria was detected in the digestive tracts of these patients compared to healthy individuals. This review article gathers information from research papers that have examined the relationship between gut microbiota composition and MS and its possible mechanisms.}, }
@article {pmid34480200, year = {2022}, author = {Wang, N and Ma, S and Fu, L}, title = {Gut Microbiota Dysbiosis as One Cause of Osteoporosis by Impairing Intestinal Barrier Function.}, journal = {Calcified tissue international}, volume = {110}, number = {2}, pages = {225-235}, pmid = {34480200}, issn = {1432-0827}, support = {82172456//National Natural Science Foundation of China/ ; JYJC201809//the Cross-disciplinary Fund Projects of the Ninth People's Hospital/ ; 20210407//Seeds Fund of Engineering Research Center of Digital Medicine of the Ministry of Education/ ; 2017ZZ01023//Shanghai Clinical Medical Center/ ; }, mesh = {Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; *Osteoporosis ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Gut microbiota (GM) dysbiosis is closely related to several metabolic diseases such as hypertension, obesity, and Alzheimer's disease. However, little is known about the causal relationship between GM dysbiosis and osteoporosis. In our work, 32 3-month-old female SD rats were randomly divided into two groups: the fecal microbiota transplantation (FMT) group and the control group. The supernatant of feces from senile osteoporotic rats was transplanted to the FMT group and the same amount of sterile saline was given to the control rats. After 12 and 24 weeks, all rats were sacrificed, and the serum, bone, fecal feces, and intestine tissue were collected for the subsequent analysis. The osteocalcin (OC), CTX, and P1NP of the FMT group increased significantly at 12 and 24 weeks compared with the control group (P < 0.05). Furthermore, the BV, BV/TV, Tb.N, and Tb.Th decreased significantly in the FMT group (P < 0.05). The alpha diversity (ACE, Chao) of the FMT group was higher than the control at 24 weeks (P < 0.05). The beta diversity was close between the FMT rats and the donor rats. In addition, GM from donor rats changed the GM composition and function of the FMT rats, which was similar to that of the donor rats at 24 weeks. The impaired intestinal structure and the decreased expression of occludin, claudin, and ZO-1 were found in FMT rats. In conclusion, GM dysbiosis by transferring the feces from senile osteoporotic rats to young rats could induce osteoporosis. The changed GM and the impaired intestinal barrier contributed to the pathogenesis of osteoporosis.}, }
@article {pmid34478286, year = {2021}, author = {Chen, S and Wu, X and Tang, S and Yin, J and Song, Z and He, X and Yin, Y}, title = {Eugenol Alleviates Dextran Sulfate Sodium-Induced Colitis Independent of Intestinal Microbiota in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {36}, pages = {10506-10514}, doi = {10.1021/acs.jafc.1c00917}, pmid = {34478286}, issn = {1520-5118}, mesh = {Animals ; *Colitis/chemically induced/drug therapy/genetics ; Colon ; Cytokines/genetics ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Eugenol ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; }, abstract = {The present study investigated the effect of eugenol (EUG) on dextran sulfate sodium (DSS)-induced colitis and explored the underlying mechanisms. C57BL/6 mice were intragastrically administered normal saline or EUG (20 mg/kg body weight) for 17 days, and colitis was induced by using 3% DSS from day 7. The results showed that EUG increased the body weight and reduced the disease activity index score and colon pathological scores in DSS-treated mice (P < 0.05). Further, EUG preserved the proinflammatory cytokines (interleukin (IL)-6, -12, -21, and -23), lowered (P < 0.05) colonic malondialdehyde (MDA), uncoupling protein 2 (UCP2) expression and p65 phosphorylation, and activated (P < 0.05) colonic kelch-like ECH-associated protein 1 and nuclear factor (erythroid-derived 2)-like 2 expressions but did not affect the intestinal microbiota in DSS-treated mice. Furthermore, EUG ameliorated colitis in antibiotic-treated mice, while fecal microbiota transplantation from EUG preadministered mice failed to ameliorate colitis. In conclusion, EUG could alleviate colitis by attenuating colonic inflammation and oxidative stress independent of intestinal microbiota.}, }
@article {pmid34473644, year = {2021}, author = {Sui, G and Jia, L and Quan, D and Zhao, N and Yang, G}, title = {Activation of the gut microbiota-kynurenine-liver axis contributes to the development of nonalcoholic hepatic steatosis in nondiabetic adults.}, journal = {Aging}, volume = {13}, number = {17}, pages = {21309-21324}, pmid = {34473644}, issn = {1945-4589}, mesh = {Adult ; Case-Control Studies ; Feces/chemistry ; Female ; *Gastrointestinal Microbiome ; Humans ; Kynurenine/*metabolism ; Liver/*metabolism ; Male ; Non-alcoholic Fatty Liver Disease/*metabolism/*pathology ; }, abstract = {The contribution of gut-liver signaling to the development of non-alcoholic hepatic steatosis (NHS) in non-diabetic adults remains unclear. We therefore performed comprehensive 16S ribosomal RNA sequencing and fecal metabolomics analyses in 32 controls and 59 non-diabetic adults with NHS and performed fecal microbiota transplantation into germ-free mice using controls and NHS patients as donors. Compared to controls, the abundance of the genera Collinsella and Acinetobacter were higher, while that of Lachnospira was lower, in NHS subjects. Fecal metabolomics analysis showed decreased L-tryptophan levels and increased abundance of the tryptophan metabolite kynurenine in individuals with NHS. Correlation analysis showed that kynurenine levels positively associated with the abundance of Collinsella and Acinetobacter. ROC analysis demonstrated that the combination of tryptophan and kynurenine could discriminate NHS patients from controls with good statistical power [P < 0.05; AUC = 0.833 (95% CI, 0.747 to 0.918)]. Supporting a key role of dysbiotic gut microbiota in NHS development, incipient hepatic steatosis and increased kynurenine levels were observed in GF mice colonized with samples from NHS patients. These results indicate that enhanced kynurenine production resulting from altered gut microbiota composition contributes to NHS in nondiabetic adults and suggest the relevance of tryptophan metabolites as diagnostic biomarkers.}, }
@article {pmid34473374, year = {2021}, author = {Liu, C and Wang, YL and Yang, YY and Zhang, NP and Niu, C and Shen, XZ and Wu, J}, title = {Novel approaches to intervene gut microbiota in the treatment of chronic liver diseases.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {10}, pages = {e21871}, doi = {10.1096/fj.202100939R}, pmid = {34473374}, issn = {1530-6860}, mesh = {Animals ; End Stage Liver Disease/*drug therapy/microbiology ; *Gastrointestinal Microbiome ; Humans ; Probiotics/*therapeutic use ; }, abstract = {Recent investigations of gut microbiota have contributed to understanding of the critical role of microbial community in pathophysiology. Dysbiosis not only causes disturbance directly to the gastrointestinal tract but also affects the liver through gut-liver axis. Various types of dysbiosis have been documented in alcoholic liver disease (ALD), nonalcoholic fatty liver disease, autoimmune hepatitis (AIH), primary sclerosing cholangitis, and may be crucial for the initiation, progression, or deterioration to end-stage liver disease. A few microbial species have been identified as the causal factors leading to these chronic illnesses that either do not have clear etiologies or lack effective treatment. Notably, cytolysin-producing Enterococcus faecalis, Klebsiella pneumoniae and Enterococcus gallinarum were defined for ALD, NASH, and AIH, respectively. These groundbreaking discoveries drive a rapid development in innovative therapeutics, such as fecal microbial transplantation and implementation of specific bacteriophages in addition to prebiotics, probiotics, or synbiotics for intervention of dysbiosis. Although most emerging interventions are in preclinical development or early clinical trials, a better delineation of specific dysbiosis in these disorders at metabolic, immunogenic, or molecular levels in establishing particular causal effects aids in modulating or correcting the microbial community which is the part of daily life for human being.}, }
@article {pmid34469716, year = {2021}, author = {Sun, WL and Li, XY and Dou, HY and Wang, XD and Li, JD and Shen, L and Ji, HF}, title = {Myricetin supplementation decreases hepatic lipid synthesis and inflammation by modulating gut microbiota.}, journal = {Cell reports}, volume = {36}, number = {9}, pages = {109641}, doi = {10.1016/j.celrep.2021.109641}, pmid = {34469716}, issn = {2211-1247}, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Bacteria/*drug effects/growth &amp; development/metabolism ; Biomarkers/blood ; Butyrates/metabolism ; Diet, High-Fat ; Disease Models, Animal ; Dysbiosis ; Fecal Microbiota Transplantation ; Flavonoids/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Hep G2 Cells ; Hepatitis/metabolism/microbiology/*prevention &amp; control ; Humans ; Inflammation Mediators/blood ; Lipids/blood ; Lipogenesis/*drug effects ; Liver/*drug effects/metabolism ; Male ; Non-alcoholic Fatty Liver Disease/metabolism/microbiology/*prevention &amp; control ; Rats, Wistar ; Rats ; }, abstract = {The relationship between poor in vivo bioavailability and effective pharmacological activity are not yet fully clarified for many flavonoids. The analysis of flavonoids-induced alterations in the gut microbiota represents a promising approach to provide useful clues to elucidate the mechanism of action. Here, we investigate the effect of myricetin supplementation on high-fat-diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats and explore the associations with the gut microbiota through high-throughput analyses. The 12-week myricetin supplementation and fecal microbiota transplantation outcomes suggest that myricetin significantly slows the development of NAFLD. Meanwhile, the anti-NAFLD effects of myricetin are associated with the modulation of the gut microbiota composition. Myricetin reduces hepatic lipid synthesis and inflammation through modulations in fecal butyric-acid-related gut microbiota and protection of the gut barrier function. This study may facilitate the elucidation of the action mechanism of flavonoids with low bioavailability.}, }
@article {pmid34463571, year = {2021}, author = {Hryckowian, AJ}, title = {Microbiome Management for the 21st Century and Beyond.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0076021}, doi = {10.1128/mSystems.00760-21}, pmid = {34463571}, issn = {2379-5077}, abstract = {As we learn about the sophisticated and far-reaching impacts that our resident microbiomes have on our biology, it is apparent that the tools we have for managing our microbiomes are rudimentary at best. For example, though antibiotics rid our microbiomes of bacterial pathogens, they target pathogens and commensals alike. Additional approaches, such as fecal microbiome transplant, seem to restore a healthy microbiome in some applications, but the mechanisms underlying this treatment and its long-term effects are poorly understood. Here, I discuss my laboratory's research, which uses two major drivers of gut microbiome ecology, diet and bacteriophages, as tools to develop new concepts and approaches for managing microbiomes. I speculate on the anticipated impacts of this research and how it will influence the way that we treat the kaleidoscope of microbe-microbe and microbe-host interactions central to our health.}, }
@article {pmid34463567, year = {2021}, author = {Harrington, V and Lau, L and Seddu, K and Suez, J}, title = {Ecology and Medicine Converge at the Microbiome-Host Interface.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0075621}, doi = {10.1128/mSystems.00756-21}, pmid = {34463567}, issn = {2379-5077}, abstract = {The human body is home to a dense and diverse population of bacteria, viruses, and eukaryotes, collectively termed the microbiome. Research on host-microbiome interactions continuously demonstrates the importance of this microbial community to human physiology and its involvement in a myriad of diseases. This, in turn, sparks great interest in developing means for beneficially modulating the microbiome, such as fecal microbiome transplantation and probiotics. However, these interventions show mixed efficacy in clinical trials and raise safety concerns. How these exogenous microorganisms interact with the microbiome might underlie the efficacy and safety of these therapeutics, yet the signaling mechanisms mediating microbe-microbe interactions between human-dwelling commensals are poorly understood. In this commentary, we discuss known and putative mechanisms of interactions between commensals in the gut and how they can be harnessed for improving microbiome-targeting therapeutics and facilitating translation of microbiome research to the clinic.}, }
@article {pmid34463082, year = {2021}, author = {Bonetto, S and Fagoonee, S and Battaglia, E and Grassini, M and Saracco, GM and Pellicano, R}, title = {Recent advances in the treatment of irritable bowel syndrome.}, journal = {Polish archives of internal medicine}, volume = {131}, number = {7-8}, pages = {709-715}, doi = {10.20452/pamw.16067}, pmid = {34463082}, issn = {1897-9483}, mesh = {Abdominal Pain ; Constipation ; Diarrhea ; Female ; Humans ; *Irritable Bowel Syndrome/therapy ; Male ; Quality of Life ; }, abstract = {Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder which presents with abdominal pain and altered bowel habits. It affects about 20% of the general population, mainly women, and has a considerable impact on the quality of life and health care costs. Four different entities of IBS have been identified: IBS with constipation (IBS‑ C), IBS with diarrhea (IBS D), IBS with a mixed pattern of constipation and diarrhea, and unclassified IBS. Although the precise pathogenesis of IBS remains unclear, its multifactorial nature is evident and includes environmental and host factors. Management of patients with this disease is challenging and a personalized approach is required. A strong, reassuring physician‑ patient relationship is crucial, followed by patient education, dietary advice, and stress reduction. For nonresponding patients, the therapeutic approach may include nonpharmacological therapies and / or pharmacotherapy. The choice of pharmacological treatment is based on the predominant symptom and a prespecified time point should be planned for effectiveness evaluation and dose adjustment. In patients with IBS‑ D, the therapeutic options include mainly antibiotics, such as rifaximin, peripheral opioid agonists, mixed opioid agonists / antagonists, bile acid sequestrants, and antagonists of serotonin 5‑ hydroxytryptamine type 3 receptors. Bulking agents and osmotic laxatives represent the first line therapy for IBS‑ C, while lubiprostone and linaclotide should be reserved for difficult to treat patients. The involvement of gastrointestinal microbiota constitutes a fascinating field of exploration as it offers the potential to be modulated by the use of probiotics, prebiotics, synbiotics as well as fecal microbiota transplantation. This review offers an updated overview on the recent advances in the treatment of IBS.}, }
@article {pmid34462268, year = {2021}, author = {Sun, K and Welty, D}, title = {Elucidation of Metabolic and Disposition Pathways for Maribavir in Nonhuman Primates through Mass Balance and Semi-Physiologically Based Modeling Approaches.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {49}, number = {11}, pages = {1025-1037}, doi = {10.1124/dmd.121.000493}, pmid = {34462268}, issn = {1521-009X}, mesh = {Animals ; Antiviral Agents/*pharmacokinetics ; Benzimidazoles/*pharmacokinetics ; Bile/chemistry/metabolism ; Biotransformation ; Caco-2 Cells ; Dealkylation ; Feces/chemistry ; Gastrointestinal Transit ; Glucuronides/metabolism ; Half-Life ; Humans ; Hydrolysis ; Kidney/metabolism ; Macaca fascicularis ; Male ; Models, Biological ; Ribonucleosides/*pharmacokinetics ; }, abstract = {Maribavir is in phase 3 clinical development for treatment of cytomegalovirus infection/disease in transplant recipients. Previous research conducted using only intact cynomolgus monkeys indicated biliary secretion as the primary elimination pathway for maribavir and that maribavir undergoes enterohepatic recirculation (EHR). To clarify the exact mechanisms of maribavir's EHR behavior, we studied its clearance pathways using intravenously administered [14]C-labeled maribavir in intact and bile duct-cannulated (BDC) monkeys and constructed a semi-physiologically based pharmacokinetic (PBPK) model. Total radioactivity metabolite profiles in plasma and excreta were quantitatively determined along with plasma maribavir concentrations. Intact animals showed significantly lower clearance and longer half-lives in both total radioactivity and parent concentration in plasma than BDC monkeys. The primary in vitro and in vivo metabolic pathway for maribavir in monkey is direct glucuronidation; N-dealkylation and renal clearance are minor pathways. In BDC monkeys, 73% of dose was recovered as maribavir glucuronides in bile, and 3% of dose was recovered as parent in bile and feces; in intact animals' feces, 58% of dose was recovered as parent, and no glucuronides were detected. Therefore, EHR of maribavir occurs through biliary secretion of maribavir glucuronides, and this is followed by hydrolysis of glucuronides in the gut lumen and subsequent reabsorption of parent. A semi-PBPK model constructed from physiologic, in vitro, and in vivo BDC monkey data is capable of projecting maribavir's pharmacokinetic and EHR behavior in intact animals after intravenous or oral dosing and could be applied to modeling other xenobiotics that are subject to similar EHR processes. SIGNIFICANCE STATEMENT: Through both mass balance and semi-physiologically based pharmacokinetic (semi-PBPK) modeling approaches, this study mechanistically and quantitatively elucidates maribavir's enterohepatic recirculation (EHR) behavior in monkeys, which occurs via extensive direct glucuronidation, biliary secretion of these glucuronides, luminal hydrolysis of glucuronides to parent, and subsequent reabsorption of the parent. The study also identifies important drug- and animal-specific parameters that determine the EHR kinetics, and the semi-PBPK model is readily applicable to other drugs that undergo similar metabolic and recirculation mechanisms.}, }
@article {pmid34462225, year = {2021}, author = {Abu El Haija, M and Ye, Y and Chu, Y and Herz, H and Linden, B and Shahi, SK and Zarei, K and Mangalam, AK and Mcelroy, SJ and Mokadem, M}, title = {Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects.}, journal = {Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery}, volume = {17}, number = {12}, pages = {1996-2006}, pmid = {34462225}, issn = {1878-7533}, support = {I01 BX004774/BX/BLRD VA/United States ; I01 CX002212/CX/CSRD VA/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; R01 AI137075/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Gastric Bypass/methods ; *Gastrointestinal Microbiome/physiology ; Mice ; Myeloid Differentiation Factor 88/genetics/*metabolism ; Obesity/surgery ; Toll-Like Receptor 4/genetics/*metabolism ; }, abstract = {BACKGROUND: Toll-like receptor 4 (TLR4) has been suggested as one of the forefront cross-communicators between the intestinal bacteria and the host to regulate inflammatory signals and energy homeostasis. High-fat diet-induced inflammation is mediated by changes in gut microbiota and requires a functional TLR-4, the deficiency of which renders mice resistant to diet-induced obesity and its associated metabolic dysfunction. Furthermore, gut microbiota was suggested to play a key role in the beneficial effects of Roux-en-Y gastric bypass (RYGB), a commonly performed bariatric procedure.<br><br>OBJECTIVES: To explore whether TLR4, myeloid differentiation factor 8 (MyD88; 1 of its key downstream signaling regulators) and gut microbiota play an integrative role in RYGB-induced metabolic outcomes.<br><br>SETTING: Animal- based study.<br><br>METHOD: We performed RYGB in TLR4 and MyD88 knock-out (KO) mice and used fecal microbiota transplant (FMT) from RYGB-operated animals to these genetic mouse models to address our questions.<br><br>RESULTS: We demonstrate that RYGB reduces TLR4 expression explicitly in the small and large intestine of C57Blc/6J mice. We also show that TLR4 KO mice have an attenuated glucoregulatory response to RYGB. In addition, we reveal that MyD88 KO mice fail to respond to all RYGB-induced metabolic effects. Finally, fecal microbiota transplant from RYGB-operated mice into TLR4 KO and MyD88 KO na&#xef;ve recipients fails to induce a metabolic phenotype similar to that of the donors, as it does in wild-type recipients.<br><br>CONCLUSION: TLR4 and MyD88 are required for RYGB-induced metabolic response that is likely&#xa0;mediated by gut microbiome.}, }
@article {pmid34461168, year = {2022}, author = {Au, EH and Wong, G and Howard, K and Chapman, JR and Castells, A and Roger, SD and Bourke, MJ and Macaskill, P and Turner, R and Lim, WH and Lok, CE and Diekmann, F and Cross, N and Sen, S and Allen, RD and Chadban, SJ and Pollock, CA and Tong, A and Teixeira-Pinto, A and Yang, JY and Kieu, A and James, L and Craig, JC}, title = {Factors Associated With Advanced Colorectal Neoplasia in Patients With CKD.}, journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation}, volume = {79}, number = {4}, pages = {549-560}, doi = {10.1053/j.ajkd.2021.07.011}, pmid = {34461168}, issn = {1523-6838}, mesh = {Colonoscopy ; *Colorectal Neoplasms/diagnosis/epidemiology ; Feces ; Humans ; Male ; Occult Blood ; Prospective Studies ; *Renal Insufficiency, Chronic/complications/epidemiology/therapy ; Risk Factors ; }, abstract = {RATIONALE &amp; OBJECTIVE: The risk of developing colorectal cancer in patients with chronic kidney disease (CKD) is twice that of the general population, but the factors associated with colorectal cancer are poorly understood. The aim of this study was to identify factors associated with advanced colorectal neoplasia in patients with CKD.<br><br>STUDY DESIGN: Prospective cohort study.<br><br>SETTING &amp; PARTICIPANTS: Patients with CKD stages 3-5, including those treated with maintenance dialysis or transplantation across 11 sites in Australia, New Zealand, Canada, and Spain, were screened for colorectal neoplasia using a fecal immunochemical test (FIT) as part of the Detecting Bowel Cancer in CKD (DETECT) Study.<br><br>EXPOSURE: Baseline characteristics for patients at the time of study enrollment were ascertained, including duration of CKD, comorbidities, and medications.<br><br>OUTCOME: Advanced colorectal neoplasia was identified through a 2-step verification process with colonoscopy following positive FIT and 2-year clinical follow-up for all patients.<br><br>ANALYTICAL APPROACH: Potential factors associated with advanced colorectal neoplasia were explored using multivariable logistic regression. Sensitivity analyses were performed using grouped LASSO (least absolute shrinkage and selection operator) logistic regression.<br><br>RESULTS: Among 1,706 patients who received FIT-based screening-791 with CKD stages 3-5 not receiving kidney replacement therapy (KRT), 418 receiving dialysis, and 497 patients with a functioning kidney transplant-117 patients (6.9%) were detected to have advanced colorectal neoplasia (54 with CKD stages 3-5 without KRT, 34 receiving dialysis, and 29 transplant recipients), including 9 colorectal cancers. The factors found to be associated with advanced colorectal neoplasia included older age (OR per year older, 1.05 [95% CI, 1.03-1.07], P<0.001), male sex (OR, 2.27 [95% CI, 1.45-3.54], P<0.001), azathioprine use (OR, 2.99 [95% CI, 1.40-6.37], P=0.005), and erythropoiesis-stimulating agent use (OR, 1.92 [95% CI, 1.22-3.03], P=0.005). Grouped LASSO logistic regression revealed similar associations between these factors and advanced colorectal neoplasia.<br><br>LIMITATIONS: Unmeasured confounding factors.<br><br>CONCLUSIONS: Older age, male sex, erythropoiesis-stimulating agents, and azathioprine were found to be significantly associated with advanced colorectal neoplasia in patients with CKD.}, }
@article {pmid34461052, year = {2022}, author = {Yang, J and Wei, H and Zhou, Y and Szeto, CH and Li, C and Lin, Y and Coker, OO and Lau, HCH and Chan, AWH and Sung, JJY and Yu, J}, title = {High-Fat Diet Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites.}, journal = {Gastroenterology}, volume = {162}, number = {1}, pages = {135-149.e2}, doi = {10.1053/j.gastro.2021.08.041}, pmid = {34461052}, issn = {1528-0012}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Azoxymethane ; Bacteria/drug effects/*metabolism ; Bacterial Translocation ; Cell Proliferation ; Cell Transformation, Neoplastic/metabolism/ultrastructure ; Colon/metabolism/*microbiology/ultrastructure ; Colorectal Neoplasms/chemically induced/metabolism/*microbiology/ultrastructure ; *Diet, High-Fat ; Disease Models, Animal ; Dysbiosis ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Genes, APC ; Germ-Free Life ; Humans ; Lysophospholipids/metabolism ; Male ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Transgenic ; Permeability ; Tumor Cells, Cultured ; Mice ; }, abstract = {BACKGROUND AND AIMS: Dietary fat intake is associated with increased risk of colorectal cancer (CRC). We examined the role of high-fat diet (HFD) in driving CRC through modulating gut microbiota and metabolites.<br><br>METHODS: HFD or control diet was fed to mice littermates in CRC mouse models of an azoxymethane (AOM) model and Apc[min/+] model, with or without antibiotics cocktail treatment. Germ-free mice for fecal microbiota transplantation were used for validation. Gut microbiota and metabolites were detected using metagenomic sequencing and high-performance liquid chromatography-mass spectrometry, respectively. Gut barrier function was determined using lipopolysaccharides level and transmission electron microscopy.<br><br>RESULTS: HFD promoted colorectal tumorigenesis in both AOM-treated mice and Apc[min/+] mice compared with control diet-fed mice. Gut microbiota depletion using antibiotics attenuated colon tumor formation in HFD-fed mice. A significant shift of gut microbiota composition with increased pathogenic bacteria Alistipessp.Marseille-P5997 and Alistipessp.5CPEGH6, and depleted probiotic Parabacteroides distasonis, along with impaired gut barrier function was exhibited in HFD-fed mice. Moreover, HFD-modulated gut microbiota promotes colorectal tumorigenesis in AOM-treated germ-free mice, indicating gut microbiota was essential in HFD-associated colorectal tumorigenesis. Gut metabolites alteration, including elevated lysophosphatidic acid, which was confirmed to promote CRC cell proliferation and impair cell junction, was also observed in HFD-fed mice. Moreover, transfer of stools from HFD-fed mice to germ-free mice without interference increased colonic cell proliferation, impaired gut barrier function, and induced oncogenic genes expression.<br><br>CONCLUSIONS: HFD drives colorectal tumorigenesis through inducing gut microbial dysbiosis, metabolomic dysregulation with elevated lysophosphatidic acid, and gut barrier dysfunction in mice.}, }
@article {pmid34460287, year = {2021}, author = {Ancona, G and Alagna, L and Lombardi, A and Palomba, E and Castelli, V and Renisi, G and Dondossola, D and Iavarone, M and Muscatello, A and Gori, A and Bandera, A}, title = {The Interplay between Gut Microbiota and the Immune System in Liver Transplant Recipients and Its Role in Infections.}, journal = {Infection and immunity}, volume = {89}, number = {11}, pages = {e0037621}, pmid = {34460287}, issn = {1098-5522}, mesh = {Bacterial Infections/*etiology/immunology ; Drug Resistance, Multiple, Bacterial ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions ; Humans ; Immune System/*physiology ; Liver Cirrhosis/complications/microbiology ; Liver Transplantation/*adverse effects ; Severity of Illness Index ; }, abstract = {Liver transplantation (LT) is a life-saving strategy for patients with end-stage liver disease, hepatocellular carcinoma, and acute liver failure. LT success can be hampered by several short-term and long-term complications. Among them, bacterial infections, especially those due to multidrug-resistant germs, are particularly frequent, with a prevalence between 19 and 33% in the first 100 days after transplantation. In the last decades, a number of studies have highlighted how the gut microbiota (GM) is involved in several essential functions to ensure intestinal homeostasis, becoming one of the most important virtual metabolic organs. The GM works through different axes with other organs, and the gut-liver axis is among the most relevant and investigated ones. Any alteration or disruption of the GM is defined as dysbiosis. Peculiar phenotypes of GM dysbiosis have been associated with several liver conditions and complications, such as chronic hepatitis, fatty liver disease, cirrhosis, and hepatocellular carcinoma. Moreover, there is growing evidence of the crucial role of the GM in shaping the immune response, both locally and systemically, against pathogens. This paves the way to the manipulation of the GM as a therapeutic instrument to modulate infectious risk and outcome. In this minireview, we provide an overview of the current understanding of the interplay between the gut microbiota and the immune system in liver transplant recipients and the role of the former in infections.}, }
@article {pmid34458158, year = {2021}, author = {Zhong, HJ and Zeng, HL and Cai, YL and Zhuang, YP and Liou, YL and Wu, Q and He, XX}, title = {Washed Microbiota Transplantation Lowers Blood Pressure in Patients With Hypertension.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {679624}, pmid = {34458158}, issn = {2235-2988}, mesh = {Animals ; Antihypertensive Agents/pharmacology/therapeutic use ; Blood Pressure ; Humans ; *Hypertension/therapy ; *Microbiota ; Retrospective Studies ; }, abstract = {BACKGROUND: Although transplantation of the fecal microbiota from normotensive donors has been shown to have an antihypertensive effect in hypertensive animal models, its effect on blood pressure in patients with hypertension is unclear. This study aimed to assess the effect of washed microbiota transplantation (WMT) from normotensive donors on blood pressure regulation in hypertensive patients.<br><br>METHODS: The clinical data of consecutive patients treated with washed microbiota transplantation (WMT) were collected retrospectively. The blood pressures of hypertensive patients before and after WMT were compared. The factors influencing the antihypertensive effect of WMT in hypertensive patients and fecal microbial composition of donors and hypertensive patients were also analyzed.<br><br>RESULTS: WMT exhibited an antihypertensive effect on blood pressure: the blood pressure at hospital discharge was significantly lower than that at hospital admission (change in systolic blood pressure: -5.09 &#xb1; 15.51, P = 0.009; change in diastolic blood pressure: -7.74 &#xb1; 10.42, P < 0.001). Hypertensive patients who underwent WMT via the lower gastrointestinal tract (&#x3b2; = -8.308, standard error = 3.856, P = 0.036) and those not taking antihypertensive drugs (&#x3b2; = -8.969, standard error = 4.256, P = 0.040) had a greater decrease in systolic blood pressure, and hypertensive patients not taking antihypertensive drugs also had a greater decrease in diastolic blood pressure (&#x3b2; = -8.637, standard error = 2.861, P = 0.004). After WMT, the Shannon Diversity Index was higher in six of eight hypertensive patients and the microbial composition of post-WMT samples tended to be closer to that of donor samples.<br><br>CONCLUSION: WMT had a blood pressure-lowering effect in hypertensive patients, especially in those who underwent WMT via the lower gastrointestinal tract and in those not taking antihypertensive drugs. Therefore, modulation of the gut microbiota by WMT may offer a novel approach for hypertension treatment.}, }
@article {pmid34455517, year = {2021}, author = {Li, JJ and Zhu, M and Kashyap, PC and Chia, N and Tran, NH and McWilliams, RR and Bekaii-Saab, TS and Ma, WW}, title = {The role of microbiome in pancreatic cancer.}, journal = {Cancer metastasis reviews}, volume = {40}, number = {3}, pages = {777-789}, pmid = {34455517}, issn = {1573-7233}, support = {R01 CA179243/CA/NCI NIH HHS/United States ; }, mesh = {*Carcinoma, Pancreatic Ductal/therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; *Pancreatic Neoplasms/therapy ; *Probiotics/therapeutic use ; Tumor Microenvironment ; }, abstract = {Recent studies of the human microbiome have offered new insights into how the microbiome can impact cancer development and treatment. Specifically, in pancreatic ductal adenocarcinoma (PDAC), the microbiota has been shown to modulate PDAC risk, contribute to tumorigenesis, impact the tumor microenvironment, and alter treatment response. These findings provide rationale for further investigations into leveraging the microbiome to develop new strategies to diagnose and treat PDAC patients. There is growing evidence that microbiome analyses have the potential to become easily performed, non-invasive diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. More excitingly, there is now emerging interest in developing interventions based on the modulation of microbiota. Fecal microbiota transplantation, probiotics, dietary changes, and antibiotics are all potential strategies to augment the efficacy of current therapeutics and reduce toxicities. While there are still challenges to overcome, this is a rapidly growing field that holds promise for translation into clinical practice and provides a new approach to improving patient outcomes.}, }
@article {pmid34453966, year = {2021}, author = {Bloom, PP and Tapper, EB and Young, VB and Lok, AS}, title = {Microbiome therapeutics for hepatic encephalopathy.}, journal = {Journal of hepatology}, volume = {75}, number = {6}, pages = {1452-1464}, pmid = {34453966}, issn = {1600-0641}, support = {K23 DK117055/DK/NIDDK NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; }, mesh = {Fecal Microbiota Transplantation/methods/statistics &amp; numerical data ; Hepatic Encephalopathy/*drug therapy ; Host Microbial Interactions/drug effects ; Humans ; Microbiota/*drug effects ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {Hepatic encephalopathy (HE) is a complication of cirrhosis characterised by neuropsychiatric and motor dysfunction. Microbiota-host interactions play an important role in HE pathogenesis. Therapies targeting microbial community composition and function have been explored for the treatment of HE. Prebiotics, probiotics and faecal microbiota transplant (FMT) have been used with the aim of increasing the abundance of potentially beneficial taxa, while antibiotics have been used to decrease the abundance of potentially harmful taxa. Other microbiome therapeutics, including postbiotics and absorbents, have been used to target microbial products. Microbiome-targeted therapies for HE have had some success, notably lactulose and rifaximin, with probiotics and FMT also showing promise. However, there remain several challenges to the effective application of microbiome therapeutics in HE, including the resilience of the microbiome to sustainable change and unpredictable clinical outcomes from microbiota alterations. Future work in this space should focus on rigorous trial design, microbiome therapy selection, and a personalised approach to HE.}, }
@article {pmid34452466, year = {2021}, author = {Desselberger, U}, title = {Significance of the Gut Microbiome for Viral Diarrheal and Extra-Intestinal Diseases.}, journal = {Viruses}, volume = {13}, number = {8}, pages = {}, pmid = {34452466}, issn = {1999-4915}, mesh = {Animals ; Bacteria/genetics ; Bacterial Physiological Phenomena ; Diarrhea/*virology ; *Diet ; Dysbiosis/*microbiology ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions ; Humans ; Intestines/pathology/virology ; Mice ; Prebiotics ; Probiotics ; }, abstract = {The composition of the mammalian gut microbiome is very important for the health and disease of the host. Significant correlations of particular gut microbiota with host immune responsiveness and various infectious and noninfectious host conditions, such as chronic enteric infections, type 2 diabetes, obesity, asthma, and neurological diseases, have been uncovered. Recently, research has moved on to exploring the causalities of such relationships. The metabolites of gut microbiota and those of the host are considered in a 'holobiontic' way. It turns out that the host's diet is a major determinant of the composition of the gut microbiome and its metabolites. Animal models of bacterial and viral intestinal infections have been developed to explore the interrelationships of diet, gut microbiome, and health/disease phenotypes of the host. Dietary fibers can act as prebiotics, and certain bacterial species support the host's wellbeing as probiotics. In cases of Clostridioides difficile-associated antibiotic-resistant chronic diarrhea, transplantation of fecal microbiomes has sometimes cured the disease. Future research will concentrate on the definition of microbial/host/diet interrelationships which will inform rationales for improving host conditions, in particular in relation to optimization of immune responses to childhood vaccines.}, }
@article {pmid34450312, year = {2021}, author = {Socała, K and Doboszewska, U and Szopa, A and Serefko, A and Włodarczyk, M and Zielińska, A and Poleszak, E and Fichna, J and Wlaź, P}, title = {The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders.}, journal = {Pharmacological research}, volume = {172}, number = {}, pages = {105840}, doi = {10.1016/j.phrs.2021.105840}, pmid = {34450312}, issn = {1096-1186}, mesh = {Animals ; *Brain-Gut Axis ; *Gastrointestinal Microbiome ; Humans ; Mental Disorders/*microbiology ; Nervous System Diseases/*microbiology ; }, abstract = {Emerging evidence indicates that the gut microbiota play a crucial role in the bidirectional communication between the gut and the brain suggesting that the gut microbes may shape neural development, modulate neurotransmission and affect behavior, and thereby contribute to the pathogenesis and/or progression of many neurodevelopmental, neuropsychiatric, and neurological conditions. This review summarizes recent data on the role of microbiota-gut-brain axis in the pathophysiology of neuropsychiatric and neurological disorders including depression, anxiety, schizophrenia, autism spectrum disorders, Parkinson's disease, migraine, and epilepsy. Also, the involvement of microbiota in gut disorders co-existing with neuropsychiatric conditions is highlighted. We discuss data from both in vivo preclinical experiments and clinical reports including: (1) studies in germ-free animals, (2) studies exploring the gut microbiota composition in animal models of diseases or in humans, (3) studies evaluating the effects of probiotic, prebiotic or antibiotic treatment as well as (4) the effects of fecal microbiota transplantation.}, }
@article {pmid34449321, year = {2021}, author = {Duan, L and An, X and Zhang, Y and Jin, D and Zhao, S and Zhou, R and Duan, Y and Zhang, Y and Liu, X and Lian, F}, title = {Gut microbiota as the critical correlation of polycystic ovary syndrome and type 2 diabetes mellitus.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {142}, number = {}, pages = {112094}, doi = {10.1016/j.biopha.2021.112094}, pmid = {34449321}, issn = {1950-6007}, mesh = {Animals ; Diabetes Mellitus, Type 2/microbiology/*physiopathology ; Dysbiosis/complications/therapy ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Polycystic Ovary Syndrome/microbiology/*physiopathology ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; }, abstract = {Gut microbiota forms a symbiotic relationship with the host and maintains the ecological balance of the internal and external environment of the human body. However, dysbiosis of the gut microbiota and immune deficiency, as well as environmental changes, can destroy the host-microbial balance, leading to the occurrence of a variety of diseases, such as polycystic ovary syndrome (PCOS), type 2 diabetes mellitus (T2DM), and obesity. Meanwhile, diseases can also affect gut microbiota, forming a vicious cycle. The role of the intestinal microbiota in different diseases have been proven by several studies; however, as a common target of PCOS and T2DM, there are few reports on the treatment of different diseases through the regulation of intestinal microbiota as the critical correlation. This review analyzed the common mechanisms of intestinal microbiota in PCOS and T2DM, including the dysbiosis of gut microbiota, endotoxemia, short-chain fatty acids, biotransformation of bile acids, and synthesis of amino acid in regulating insulin resistance, obesity, chronic inflammation, and mitochondrial dysfunction. The possible therapeutic effects of probiotics and/or prebiotics, fecal microbiota transplantation, bariatric surgery, dietary intervention, drug treatment, and other treatments targeted at regulating intestinal microbiota were also elucidated.}, }
@article {pmid34448411, year = {2021}, author = {Wertman, JN and Dunn, KA and Kulkarni, K}, title = {The impact of the host intestinal microbiome on carcinogenesis and the response to chemotherapy.}, journal = {Future oncology (London, England)}, volume = {17}, number = {32}, pages = {4371-4387}, doi = {10.2217/fon-2021-0087}, pmid = {34448411}, issn = {1744-8301}, support = {IWK Research Associateship, Post Doctoral Fellowship//IWK Health Centre/ ; }, mesh = {Antineoplastic Agents/adverse effects ; Asparaginase/therapeutic use ; Carcinogenesis ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Neoplasms/drug therapy/*etiology/microbiology ; }, abstract = {The microbiome consists of all microbes present on and within the human body. An unbalanced, or 'dysbiotic' intestinal microbiome is associated with inflammatory bowel disease, diabetes and some cancer types. Drug treatment can alter the intestinal microbiome composition. Additionally, some chemotherapeutics interact with microbiome components, leading to changes in drug safety and/or efficacy. The intestinal microbiome is a modifiable target, using strategies such as antibiotic treatment, fecal microbial transplantation or probiotic administration. Understanding the impact of the microbiome on the safety and efficacy of cancer treatment may result in improved treatment outcome. The present review seeks to summarize relevant research and look to the future of cancer treatment, where the intestinal microbiome is recognized as an actionable treatment target.}, }
@article {pmid34447287, year = {2021}, author = {Zhang, L and Chu, J and Hao, W and Zhang, J and Li, H and Yang, C and Yang, J and Chen, X and Wang, H}, title = {Gut Microbiota and Type 2 Diabetes Mellitus: Association, Mechanism, and Translational Applications.}, journal = {Mediators of inflammation}, volume = {2021}, number = {}, pages = {5110276}, pmid = {34447287}, issn = {1466-1861}, mesh = {*Diabetes Mellitus, Type 2/metabolism ; Fatty Acids, Volatile ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; *Probiotics/therapeutic use ; }, abstract = {Gut microbiota has attracted widespread attention due to its crucial role in disease pathophysiology, including type 2 diabetes mellitus (T2DM). Metabolites and bacterial components of gut microbiota affect the initiation and progression of T2DM by regulating inflammation, immunity, and metabolism. Short-chain fatty acids, secondary bile acid, imidazole propionate, branched-chain amino acids, and lipopolysaccharide are the main molecules related to T2DM. Many studies have investigated the role of gut microbiota in T2DM, particularly those butyrate-producing bacteria. Increasing evidence has demonstrated that fecal microbiota transplantation and probiotic capsules are useful strategies in preventing diabetes. In this review, we aim to elucidate the complex association between gut microbiota and T2DM inflammation, metabolism, and immune disorders, the underlying mechanisms, and translational applications of gut microbiota. This review will provide novel insight into developing individualized therapy for T2DM patients based on gut microbiota immunometabolism.}, }
@article {pmid34446936, year = {2022}, author = {Zarubova, K and Fabian, O and Hradsky, O and Lerchova, T and Mikus, F and Dotlacil, V and Pos, L and Skaba, R and Bronsky, J}, title = {Predictive value of tissue calprotectin for disease recurrence after ileocecal resection in pediatric Crohn's disease.}, journal = {Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia}, volume = {166}, number = {3}, pages = {297-303}, pmid = {34446936}, issn = {1804-7521}, mesh = {Biomarkers ; Child ; Colonoscopy ; *Crohn Disease/diagnosis/surgery ; Feces ; Humans ; Leukocyte L1 Antigen Complex ; Margins of Excision ; *Peritonitis ; Recurrence ; }, abstract = {AIM: Detection of possible predictive factors of endoscopic recurrence after ileocecal resection in Crohn's disease could be very beneficial for the individual adjustment of postoperative therapy. The aim of this study was to verify, whether immunohistochemical detection of calprotectin in resection margins is useful in diagnostics of endoscopic recurrence.<br><br>METHODS: In this study we included pediatric patients with Crohn's disease who underwent ileocecal resection, regardless of pre-operative or post-operative therapy (n=48). We collected laboratory, clinical, surgical, endoscopic and histopathological data at the time of surgery and at 6 months after surgery. The immunohistochemical staining of calprotectin antigen was performed on all paraffin blocks from the resection margins.<br><br>RESULTS: Out of 48 patients 52% had endoscopic recurrence in the anastomosis (defined by Rutgeerts score) within 6 months after surgery. The number of cells positive for calprotectin in the proximal resection margin was negatively associated with recurrence (P=0.008), as was the elevated level of total calprotectin (from both resection margins). There was no correlation of calprotectin in distal resection margin and endoscopic recurrence. Fecal calprotectin over 100 ug/g (P=0.0005) and high CRP (P<0.001) at 6 months after ileocecal resection and peritonitis (P=0.048) were associated with endoscopic recurrence.<br><br>CONCLUSION: Approximately half of the patients developed endoscopic recurrence within 6 months after ileocecal resection. The predictive value of tissue calprotectin is questionable, as it is negatively associated with endoscopic recurrence. There are other potentially useful predictors, such as CRP and fecal calprotectin at 6 months after resection and the presence of peritonitis.}, }
@article {pmid34444932, year = {2021}, author = {Gibiino, G and Sartini, A and Gitto, S and Binda, C and Sbrancia, M and Coluccio, C and Sambri, V and Fabbri, C}, title = {The Other Side of Malnutrition in Inflammatory Bowel Disease (IBD): Non-Alcoholic Fatty Liver Disease.}, journal = {Nutrients}, volume = {13}, number = {8}, pages = {}, pmid = {34444932}, issn = {2072-6643}, mesh = {Colitis, Ulcerative/epidemiology ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*epidemiology ; Intestines/pathology ; Male ; Malnutrition/*epidemiology ; Metabolic Syndrome/epidemiology ; Non-alcoholic Fatty Liver Disease/*epidemiology/therapy ; Nutritional Status ; Obesity/epidemiology ; Prevalence ; Risk Factors ; }, abstract = {Steatohepatitis and hepatobiliary manifestations constitute some of the most common extra-intestinal manifestations of Inflammatory Bowel Disease (IBD). On the other hand, non-alcoholic fatty liver disease (NAFLD) affects around 25% of the world's population and is attracting ever more attention in liver transplant programs. To outline the specific pathways linking these two conditions is a pressing task for 21st-century researchers. We are accustomed to expecting the occurrence of fatty liver disease in obese people, but current evidence suggests that there are several different pathways also occurring in underweight patients. Genetic factors, inflammatory signals and microbiota are key players that could help in understanding the entire pathogenesis of NAFLD, with the aim of defining the multiple expressions of malnutrition. In the current review, we summarize the most recent literature regarding the epidemiology, pathogenesis and future directions for the management of NAFLD in patients affected by IBD.}, }
@article {pmid34440855, year = {2021}, author = {Balaphas, A and Meyer, J and Meier, RPH and Liot, E and Buchs, NC and Roche, B and Toso, C and Bühler, LH and Gonelle-Gispert, C and Ris, F}, title = {Cell Therapy for Anal Sphincter Incontinence: Where Do We Stand?.}, journal = {Cells}, volume = {10}, number = {8}, pages = {}, pmid = {34440855}, issn = {2073-4409}, support = {PRD 19-I-2020//H&#xf4;pitaux Universitaires de Gen&#xe8;ve/ ; }, mesh = {Adipose Tissue/cytology ; Animals ; Bone Marrow Cells/cytology ; Cell- and Tissue-Based Therapy/*methods ; Fecal Incontinence/pathology/*therapy ; Humans ; Multipotent Stem Cells/cytology/metabolism/*transplantation ; Stem Cell Transplantation ; Stem Cells/cytology/metabolism ; }, abstract = {Anal sphincter incontinence is a chronic disease, which dramatically impairs quality of life and induces high costs for the society. Surgery, considered as the best curative option, shows a disappointing success rate. Stem/progenitor cell therapy is pledging, for anal sphincter incontinence, a substitute to surgery with higher efficacy. However, the published literature is disparate. Our aim was to perform a review on the development of cell therapy for anal sphincter incontinence with critical analyses of its pitfalls. Animal models for anal sphincter incontinence were varied and tried to reproduce distinct clinical situations (acute injury or healed injury with or without surgical reconstruction) but were limited by anatomical considerations. Cell preparations used for treatment, originated, in order of frequency, from skeletal muscle, bone marrow or fat tissue. The characterization of these preparations was often incomplete and stemness not always addressed. Despite a lack of understanding of sphincter healing processes and the exact mechanism of action of cell preparations, this treatment was evaluated in 83 incontinent patients, reporting encouraging results. However, further development is necessary to establish the correct indications, to determine the most-suited cell type, to standardize the cell preparation method and to validate the route and number of cell delivery.}, }
@article {pmid34439657, year = {2021}, author = {Abuaish, S and Al-Otaibi, NM and Abujamel, TS and Alzahrani, SA and Alotaibi, SM and AlShawakir, YA and Aabed, K and El-Ansary, A}, title = {Fecal Transplant and Bifidobacterium Treatments Modulate Gut Clostridium Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism.}, journal = {Brain sciences}, volume = {11}, number = {8}, pages = {}, pmid = {34439657}, issn = {2076-3425}, support = {RGP-1441-0027//Deanship of Scientific Research, Princess Nourah bint Abdulrahman University, the Research Group Program/ ; }, abstract = {Autism is associated with gastrointestinal dysfunction and gut microbiota dysbiosis, including an overall increase in Clostridium. Modulation of the gut microbiota is suggested to improve autistic symptoms. In this study, we explored the implementation of two different interventions that target the microbiota in a rodent model of autism and their effects on social behavior: the levels of different fecal Clostridium spp., and hippocampal transcript levels. Autism was induced in young Sprague Dawley male rats using oral gavage of propionic acid (PPA) for three days, while controls received saline. PPA-treated animals were divided to receive either saline, fecal transplant from healthy donor rats, or Bifidobacterium for 22 days, while controls continued to receive saline. We found that PPA attenuated social interaction in animals, which was rescued by the two interventions. PPA-treated animals had a significantly increased abundance of fecal C. perfringens with a concomitant decrease in Clostridium cluster IV, and exhibited high hippocampal Bdnf expression compared to controls. Fecal microbiota transplantation or Bifidobacterium treatment restored the balance of fecal Clostridium spp. and normalized the level of Bdnf expression. These findings highlight the involvement of the gut-brain axis in the etiology of autism and propose possible interventions in a preclinical model of autism.}, }
@article {pmid34438613, year = {2021}, author = {Xie, W and Kordt, M and Palme, R and Grambow, E and Vollmar, B and Zechner, D}, title = {Diagnostic Ability of Methods Depicting Distress of Tumor-Bearing Mice.}, journal = {Animals : an open access journal from MDPI}, volume = {11}, number = {8}, pages = {}, pmid = {34438613}, issn = {2076-2615}, support = {ZE 712/1-1, ZE 712/1-2, VO 450/15-1 and VO 450/15-2//Deutsche Forschungsgemeinschaft/ ; ESF/14-BM-A55-0003/18//European Social Fund/ ; }, abstract = {Subcutaneous tumor models in mice are the most commonly used experimental animal models in cancer research. To improve animal welfare and the quality of scientific studies, the distress of experimental animals needs to be minimized. For this purpose, one must assess the diagnostic ability of readout parameters to evaluate distress. In this study, we evaluated different noninvasive readout parameters such as body weight change, adjusted body weight change, faecal corticosterone metabolites concentration, burrowing activity and a distress score by utilising receiver operating characteristic curves. Eighteen immunocompromised NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice were used for this study; half were subcutaneously injected with A-375 cells (human malignant melanoma cells) that resulted in large tumors. The remaining mice were inoculated with SCL-2 cells (cutaneous squamous cell carcinoma cells), which resulted in small tumors. The adjusted body weight and faecal corticosterone metabolites concentration had a high diagnostic ability in distinguishing between mice before cancer cell injection and mice bearing large tumors. All other readout parameters had a low diagnostic ability. These results suggest that adjusted body weight and faecal corticosterone metabolites are useful to depict the distress of mice bearing large subcutaneous tumors.}, }
@article {pmid34436434, year = {2021}, author = {Murphy, K and O'Donovan, AN and Caplice, NM and Ross, RP and Stanton, C}, title = {Exploring the Gut Microbiota and Cardiovascular Disease.}, journal = {Metabolites}, volume = {11}, number = {8}, pages = {}, pmid = {34436434}, issn = {2218-1989}, support = {SFI/12/RC/2273-P2/SFI_/Science Foundation Ireland/Ireland ; SFI/16/RC/3835/SFI_/Science Foundation Ireland/Ireland ; }, abstract = {Cardiovascular disease (CVD) has been classified as one of the leading causes of morbidity and mortality worldwide. CVD risk factors include smoking, hypertension, dyslipidaemia, obesity, inflammation and diabetes. The gut microbiota can influence human health through multiple interactions and community changes are associated with the development and progression of numerous disease states, including CVD. The gut microbiota are involved in the production of several metabolites, such as short-chain fatty acids (SCFAs), bile acids and trimethylamine-N-oxide (TMAO). These products of microbial metabolism are important modulatory factors and have been associated with an increased risk of CVD. Due to its association with CVD development, the gut microbiota has emerged as a target for therapeutic approaches. In this review, we summarise the current knowledge on the role of the gut microbiome in CVD development, and associated microbial communities, functions, and metabolic profiles. We also discuss CVD therapeutic interventions that target the gut microbiota such as probiotics and faecal microbiota transplantation.}, }
@article {pmid34431607, year = {2021}, author = {Klang, E and Barash, Y and Soffer, S and Shachar, E and Lahat, A}, title = {Trends in inflammatory bowel disease treatment in the past two decades-a high-level text mining analysis of PubMed publications.}, journal = {United European gastroenterology journal}, volume = {9}, number = {9}, pages = {1019-1026}, pmid = {34431607}, issn = {2050-6414}, mesh = {Biological Products/therapeutic use ; Complementary Therapies ; Data Mining/*methods ; Diet ; Fecal Microbiota Transplantation ; Humans ; Incidence ; Inflammatory Bowel Diseases/epidemiology/microbiology/*therapy ; Microbiota ; Prevalence ; Probiotics/therapeutic use ; *PubMed ; }, abstract = {AIM: Many therapeutic options for inflammatory bowel disease (IBD) emerged during the last 2 decades, along with the rise in disease prevalence and incidence. We aimed at assessing the published literature on different treatment options in that period. Special attention was attributed to specific medication mechanisms and geographic diversity.<br><br>MATERIALS AND METHODS: We have queried PubMed for all available IBD-related entries published during 2000-2020. The following data were extracted for each entry: PubMed unique article ID (PMID), title, publishing journal, abstract text, keywords (if any), and authors' affiliations. Two gastrointestinal specialists decided in consensus on a list of terms to classify entries. The terms belonged to five treatment groups: medical, surgical, dietary, microbiome manipulation, and complementary medicine. The medical and complementary medicine groups were further sub-classified. Annual trends of publications for the years 2000-2020 were plotted for different treatment types. The slopes of publication trends were calculated by fitting regression lines to the annual number of publications.<br><br>RESULTS: Overall, 77,505 IBD entries were published between 2000 and 2020. Medical treatment showed the highest number of total publications 21,540/77,505 (27.8%), followed by surgical 7605/77,505 (9.8%), microbiome research 5260/77,505 (6.8%), dietary 4819/77,505 (6.2%), and complementary medicine treatment 762/77,505 (1.0%). Interestingly, since 2012 there is a steep rise in microbiome publications that outnumbered surgery in the last 2&#xa0;years. Trend analysis of medical treatment showed that biologics had the steepest slope (57.5, p&#xa0;<&#xa0;0.001), followed by immunomodulators (4.9, p&#xa0;<&#xa0;0.001), small molecules (3.9, p&#xa0;<&#xa0;0.001), and 5-ASA (3.8, p&#xa0;<&#xa0;0.001).<br><br>CONCLUSION: According to our high-level publications trend analysis, the past 2&#xa0;decades certainly deserve the reference as the "biologic era", as publications regarding biological therapy outnumbered all other treatment options. Interestingly, though very popular among patients, complementary medicine was not studied with correlation to its' acceptance among patients.}, }
@article {pmid34430117, year = {2021}, author = {Nandwana, V and Debbarma, S}, title = {Fecal Microbiota Transplantation: A Microbiome Modulation Technique for Alzheimer's Disease.}, journal = {Cureus}, volume = {13}, number = {7}, pages = {e16503}, pmid = {34430117}, issn = {2168-8184}, abstract = {Alzheimer's disease (AD) is the most common form of dementia and the fifth leading cause of death among the elderly. AD involves parts of the brain that can lead to progressive memory loss and impaired language skills and cognitive thinking, affecting one's ability to carry out daily activities. Aging, bad dietary habits, family history, as well as altered gut microbiota composition may play a role in the pathogenesis of AD. Although the association between the imbalance of gut microbiota and AD is still difficult to determine, it has been suggested that dysbiosis can lead to the increased secretion of lipopolysaccharides and amyloid, which may impair the permeability of the intestine and the blood-brain barrier. Moreover, it can progress the process of neuroinflammation, amyloid-beta formation, and ultimately neuronal death. Microbiota-targeted interventions such as personalized diet, probiotics, or fecal microbiota transplantation (FMT) might represent a potential therapeutic option for AD. This review article discusses the procedure of FMT and its possible side effects on the recipient's body. In addition, we review the role of FMT in the context of its application in various nervous system-related disorders (AD, Parkinson's disease, multiple sclerosis).}, }
@article {pmid34428426, year = {2021}, author = {Jiao, X and Pei, X and Lu, D and Qi, D and Huang, S and He, S and Li, Z}, title = {Microbial Reconstitution Improves Aging-Driven Lacrimal Gland Circadian Dysfunction.}, journal = {The American journal of pathology}, volume = {191}, number = {12}, pages = {2091-2116}, doi = {10.1016/j.ajpath.2021.08.006}, pmid = {34428426}, issn = {1525-2191}, mesh = {Aging/pathology/*physiology ; Animals ; Chronobiology Disorders/etiology/therapy ; Circadian Rhythm/physiology ; Dysbiosis/etiology/therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/physiology ; Lacrimal Apparatus/physiology/physiopathology ; Lacrimal Apparatus Diseases/etiology/*therapy ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Transcriptome ; }, abstract = {Lacrimal glands are highly susceptible to aging and exhibit age-related structural and functional alterations. However, the mechanisms by which aging affects the lacrimal glands are not well-established. The current study explores the crosstalk between the aging process, gut microbiota, and circadian rhythm in age-associated lacrimal gland dysfunction. C57BL/6J mice were divided into young, old, and fecal microbiota transplant (FMT)-treated old groups. The gut bacterial community diversity was analyzed by 16S rRNA sequencing. Exorbital lacrimal glands (ELGs) were collected at 3-hour intervals over a 24-hour circadian cycle, and total RNA was subjected to high-throughput sequencing. Rhythmic transcriptional data were analyzed using the Jonckheere-Terpstra-Kendall algorithm and bioinformatics analysis technology. Immunostaining was used to identify lymphocytic infiltration, lipid deposition, and nerve innervation in the ELGs. Compared with young mice, old mice underwent a significant gut microbial community shift. The rhythmically transcriptomic profile was significantly reprogrammed over a 24-hour cycle in the old ELG group. Intervention with serial FMT from young donors for 1 month rejuvinated the gut microbial community of the old mice. Most alterations in rhythmic transcriptomic profiling were improved. Furthermore, chronic inflammation, lipid deposition, and aberrant neural response of the aging lacrimal glands were significantly reduced. Thus, the study shows that reconstitution of age-associated gut dysbiosis with FMTs from young donors improves aging-driven lacrimal gland circadian dysfunction.}, }
@article {pmid34426641, year = {2021}, author = {Samuelson, DR and Gu, M and Shellito, JE and Molina, PE and Taylor, CM and Luo, M and Welsh, DA}, title = {Pulmonary immune cell trafficking promotes host defense against alcohol-associated Klebsiella pneumonia.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {997}, pmid = {34426641}, issn = {2399-3642}, support = {P60 AA009803/AA/NIAAA NIH HHS/United States ; R21 AA027199/AA/NIAAA NIH HHS/United States ; K99 AA026336/AA/NIAAA NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; P50 AA009803/AA/NIAAA NIH HHS/United States ; UH2 AA026226/AA/NIAAA NIH HHS/United States ; R00 AA026336/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Ethanol/*adverse effects ; Female ; Gastrointestinal Microbiome/*physiology ; Immunity/drug effects ; Indoles/pharmacology ; Klebsiella/*physiology ; Klebsiella Infections/*immunology ; Lung/drug effects/microbiology ; Mice ; Mice, Inbred C57BL ; Pneumonia/*immunology ; Probiotics/pharmacology ; }, abstract = {The intestinal microbiota generates many different metabolites which are critical for the regulation of host signaling pathways. In fact, a wide-range of diseases are associated with increased levels of local or systemic microbe-derived metabolites. In contrast, certain bacterial metabolites, such as tryptophan metabolites, are known to contribute to both local and systemic homeostasis. Chronic alcohol consumption is accompanied by alterations to intestinal microbial communities, and their functional capacities. However, little is known about the role of alcohol-associated dysbiosis on host defense against bacterial pneumonia. Our previous work using fecal transplantation demonstrated that alcohol-associated intestinal dysbiosis, independent of ethanol consumption, increased susceptibility to Klebsiella pneumonia. Here, we demonstrate that intestinal microbiota treatments mitigate the increased risk of alcohol-associated pneumonia. Treatment with the microbial metabolite indole or with probiotics reduced pulmonary and extrapulmonary bacterial burden, restored immune responses, and improved cellular trafficking required for host defense. Protective effects were, in part, mediated by aryl hydrocarbon receptors (AhR), as inhibition of AhR diminished the protective effects. Thus, alcohol appears to impair the production/processing of tryptophan catabolites resulting in immune dysregulation and impaired cellular trafficking. These data support microbiota therapeutics as novel strategies to mitigate the increased risk for alcohol-associated bacterial pneumonia.}, }
@article {pmid34426438, year = {2021}, author = {Hajda, J and Leuchs, B and Angelova, AL and Frehtman, V and Rommelaere, J and Mertens, M and Pilz, M and Kieser, M and Krebs, O and Dahm, M and Huber, B and Engeland, CE and Mavratzas, A and Hohmann, N and Schreiber, J and Jäger, D and Halama, N and Sedlaczek, O and Gaida, MM and Daniel, V and Springfeld, C and Ungerechts, G}, title = {Phase 2 Trial of Oncolytic H-1 Parvovirus Therapy Shows Safety and Signs of Immune System Activation in Patients With Metastatic Pancreatic Ductal Adenocarcinoma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {27}, number = {20}, pages = {5546-5556}, doi = {10.1158/1078-0432.CCR-21-1020}, pmid = {34426438}, issn = {1557-3265}, mesh = {Adenocarcinoma/*secondary/*therapy ; Aged ; Carcinoma, Pancreatic Ductal/*secondary/*therapy ; *H-1 parvovirus ; Humans ; Immune System/*immunology ; Middle Aged ; *Oncolytic Virotherapy/adverse effects ; Pancreatic Neoplasms/*pathology/*therapy ; }, abstract = {PURPOSE: To investigate the safety, clinical efficacy, virus pharmacokinetics, shedding, and immune response after administration of an oncolytic parvovirus (H-1PV, ParvOryx) to patients with metastatic pancreatic ductal adenocarcinoma (PDAC) refractory to first-line therapy.<br><br>PATIENTS AND METHODS: This is a noncontrolled, single-arm, open-label, dose-escalating, single-center clinical trial. Seven patients with PDAC and at least one liver metastasis were included. ParvOryx was administered intravenously on 4 consecutive days and as an intralesional injection, 6 to 13 days thereafter. Altogether, three escalating dose levels were investigated. In addition, gemcitabine treatment was initiated on day 28.<br><br>RESULTS: ParvOryx showed excellent tolerability with no dose-limiting toxicities. One patient had a confirmed partial response and one patient revealed an unconfirmed partial response according to RECIST criteria. Both patients showed remarkably long surivial of 326 and 555 days, respectively. Investigation of pharmacokinetics and virus shedding revealed dose dependency with no excretion of active virus particles in saliva or urine and very limited excretion in feces. H-1PV nucleic acids were detected in tumor samples of four patients. All patients showed T-cell responses to viral proteins. An interesting immunologic pattern developed in tumor tissues and in blood of both patients with partial response suggesting immune activation after administration of ParvOryx.<br><br>CONCLUSIONS: The trial met all primary objectives, revealed no environmental risks, and indicated favorable immune modulation after administration of ParvOryx. It can be considered a good basis for further systematic clinical development alone or in combination with immunomodulatory compounds.}, }
@article {pmid34425028, year = {2022}, author = {Osatakul, S and Benninga, MA and Thapar, N and Treepongkaruna, S and Puetpaiboon, A}, title = {The magnitude and management of functional constipation at pediatric gastroenterology clinics: A survey study of various countries.}, journal = {Journal of gastroenterology and hepatology}, volume = {37}, number = {1}, pages = {89-96}, doi = {10.1111/jgh.15671}, pmid = {34425028}, issn = {1440-1746}, mesh = {Ambulatory Care Facilities ; Child ; *Constipation/epidemiology/therapy ; *Gastroenterology ; Global Health/statistics &amp; numerical data ; Humans ; *Pediatrics ; Polyethylene Glycols/therapeutic use ; Surveys and Questionnaires ; }, abstract = {BACKGROUND AND AIM: There have been no large-scale epidemiological study of functional constipation of pediatric gastroenterology services. This survey was undertaken to investigate the prevalence of functional constipation and magnitude of related problems in hospital settings of various countries as well as the practice of pediatric gastroenterologists in management of these conditions.<br><br>METHODS: The survey was conducted by sending questionnaires to members of Societies for Pediatric Gastroenterology Hepatology and Nutrition of various continents.<br><br>RESULTS: A total of 274 pediatric gastroenterologists from 41 countries participated in this study. Functional constipation accounted for overall 30% of patients attending pediatric gastroenterology outpatient clinics. In comparison with non-western countries, respondents from western countries reported significantly higher median annual numbers of new patients with intractable functional constipation (10 [4,25] vs 5 [2,10], P < 0.001), dyssynergic defecation (3 [0,15] vs 1 [0,4], P < 0.001), and colonic inertia (2 [0,5] vs 0 [0,1], P < 0.001). The use of high dose polyethylene glycol for fecal disimpaction was significantly more commonly among respondents from western countries, whereas rectal enema was significantly more favored in non-western countries. Respondents from different continents reported significant discrepancies in choices of investigations and management of patients with dyssynergic defecation and colonic inertia.<br><br>CONCLUSIONS: Functional constipation is a major problem for pediatric gastroenterology outpatient services worldwide. There were significant variations in the investigations of choice and therapeutic management of functional constipation, intractable functional constipation, and related problems among pediatric gastroenterologists of different geographic regions.}, }
@article {pmid34424831, year = {2021}, author = {de Wouters d'Oplinter, A and Rastelli, M and Van Hul, M and Delzenne, NM and Cani, PD and Everard, A}, title = {Gut microbes participate in food preference alterations during obesity.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1959242}, pmid = {34424831}, issn = {1949-0984}, mesh = {Animals ; Bacteroidetes/classification/isolation &amp; purification ; Brain-Gut Axis/*physiology ; Corpus Striatum/metabolism ; Diet, High-Fat ; Fecal Microbiota Transplantation ; Feeding Behavior/*physiology ; Food Preferences/*physiology ; Gastrointestinal Microbiome/*physiology ; Hyperphagia/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/*microbiology ; Reward ; }, abstract = {Hypothalamic regulations of food intake are altered during obesity. The dopaminergic mesocorticolimbic system, responsible for the hedonic response to food intake, is also affected. Gut microbes are other key players involved in obesity. Therefore, we investigated whether the gut microbiota plays a causal role in hedonic food intake alterations contributing to obesity. We transferred fecal material from lean or diet-induced obese mice into recipient mice and evaluated the hedonic food intake using a food preference test comparing the intake of control and palatable diets (HFHS, High-Fat High-Sucrose) in donor and recipient mice. Obese mice ate 58% less HFHS during the food preference test (p < 0.0001) than the lean donors, suggesting a dysregulation of the hedonic food intake during obesity. Strikingly, the reduction of the pleasure induced by eating during obesity was transferable through gut microbiota transplantation since obese gut microbiota recipient mice exhibited similar reduction in HFHS intake during the food preference test (40% reduction as compared to lean gut microbiota recipient mice, p < 0.01). This effect was associated with a consistent trend in modifications of dopaminergic markers expression in the striatum. We also pinpointed a highly positive correlation between HFHS intake and Parabacteroides (p < 0.0001), which could represent a potential actor involved in hedonic feeding probably through the gut-to-brain axis. We further demonstrated the key roles played by gut microbes in this paradigm since depletion of gut microbiota using broad-spectrum antibiotics also altered HFHS intake during food preference test in lean mice. In conclusion, we discovered that gut microbes regulate hedonic aspects of food intake. Our data demonstrate that gut microbiota modifications associated with obesity participate in dysregulations of the reward and hedonic components of the food intake. These data provide evidence that gut microbes could be an interesting therapeutic target to tackle hedonic disorders related to obesity.}, }
@article {pmid34424357, year = {2022}, author = {Schiereck, T and Yeldan, S and Kranz, J and Schneidewind, L and Wagenlehner, F and Wieters, I and Vehreschild, MJGT and Otto, T and Barski, D}, title = {[Urinary bladder microbiome analysis and probiotic treatment options for women with recurrent urinary tract infections].}, journal = {Der Urologe. Ausg. A}, volume = {61}, number = {1}, pages = {41-51}, pmid = {34424357}, issn = {1433-0563}, mesh = {Anti-Bacterial Agents/therapeutic use ; Female ; Humans ; *Microbiota ; *Probiotics/therapeutic use ; Urinary Bladder ; *Urinary Tract Infections/drug therapy/prevention &amp; control ; }, abstract = {Novel preventive measures and therapeutic approaches are needed to reduce the frequency of recurrent urinary tract infections (rUTI) and the associated emergence of multidrug-resistant uropathogens. The aim of this review is to systematically present the available evidence on the urinary bladder microbiome of healthy women and those with rUTIs. In addition, relevant studies on the efficacy of probiotics in rUTIs are presented in a structured manner. This will provide an overview on the current state of research and an outlook on treatment strategies beyond the usual antimicrobial options.}, }
@article {pmid34423918, year = {2022}, author = {Loeser, RF and Arbeeva, L and Kelley, K and Fodor, AA and Sun, S and Ulici, V and Longobardi, L and Cui, Y and Stewart, DA and Sumner, SJ and Azcarate-Peril, MA and Sartor, RB and Carroll, IM and Renner, JB and Jordan, JM and Nelson, AE}, title = {Association of Increased Serum Lipopolysaccharide, But Not Microbial Dysbiosis, With Obesity-Related Osteoarthritis.}, journal = {Arthritis &amp; rheumatology (Hoboken, N.J.)}, volume = {74}, number = {2}, pages = {227-236}, pmid = {34423918}, issn = {2326-5205}, support = {P30-DK-056350/DK/NIDDK NIH HHS/United States ; P30-DK-034987/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30-AR-072580/AR/NIAMS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U01DP006266/ACL/ACL HHS/United States ; UL1-TR-002489/TR/NCATS NIH HHS/United States ; /ARTHFN/ARTHFN/United States ; P40-OD-010995//Office of the Director, NIH/ ; P30 AR072580/AR/NIAMS NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; U01 DP006266/DP/NCCDPHP CDC HHS/United States ; U01-DP-006266/CC/CDC HHS/United States ; P30-DK-056350//Nutrition Obesity Resource Core of the National Institute of Diabetes and Digestive and Kidney Diseases/ ; P30 DK056350/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Dysbiosis/*complications ; Feces/microbiology ; Humans ; Lipopolysaccharides/*blood ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/*complications ; Osteoarthritis, Knee/*blood/*etiology ; }, abstract = {OBJECTIVE: To test the hypothesis that an altered gut microbiota (dysbiosis) plays a role in obesity-associated osteoarthritis (OA).<br><br>METHODS: Stool and blood samples were collected from 92 participants with a body mass index (BMI) &#x2265;30 kg/m[2] , recruited from the Johnston County Osteoarthritis Project. OA patients (n&#x2009;=&#x2009;50) had hand and knee OA (Kellgren/Lawrence [K/L] grade&#x2009;&#x2265;2 or arthroplasty). Controls (n&#x2009;=&#x2009;42) had no hand OA and a K/L grade of 0-1 for the knees. Compositional analysis of stool samples was carried out by 16S ribosomal RNA amplicon sequencing. Alpha- and beta-diversity and differences in taxa relative abundances were determined. Blood samples were used for multiplex cytokine analysis and measures of lipopolysaccharide (LPS) and LPS binding protein. Germ-free mice were gavaged with patient- or control-pooled fecal samples and fed a 40% fat, high-sucrose diet for 40&#x2009;weeks. Knee OA was evaluated histologically.<br><br>RESULTS: On average, OA patients were slightly older than the controls, consisted of more women, and had a higher mean BMI, higher mean Western Ontario and McMaster Universities Osteoarthritis Index pain score, and higher mean K/L grade. There were no significant differences in &#x3b1;- or &#x3b2;-diversity or genus level composition between patients and controls. Patients had higher plasma levels of osteopontin (P&#x2009;=&#x2009;0.01) and serum LPS (P&#x2009;<&#x2009;0.0001) compared to controls. Mice transplanted with patient or control microbiota exhibited a significant difference in &#x3b1;-diversity (P&#x2009;=&#x2009;0.02) and &#x3b2;-diversity, but no differences in OA severity were observed.<br><br>CONCLUSION: The lack of differences in the gut microbiota, but increased serum LPS levels, suggest the possibility that increased intestinal permeability allowing for greater absorption of LPS, rather than a dysbiotic microbiota, may contribute to the development of OA associated with obesity.}, }
@article {pmid34419965, year = {2021}, author = {Kullberg, RFJ and Wiersinga, WJ and Haak, BW}, title = {Gut microbiota and sepsis: from pathogenesis to novel treatments.}, journal = {Current opinion in gastroenterology}, volume = {37}, number = {6}, pages = {578-585}, doi = {10.1097/MOG.0000000000000781}, pmid = {34419965}, issn = {1531-7056}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Probiotics/therapeutic use ; *Sepsis/therapy ; }, abstract = {PURPOSE OF REVIEW: This review summarizes recent progress in our understanding of the role of the gut microbiota in sepsis pathogenesis and outlines the potential role of microbiota-targeted therapies.<br><br>RECENT FINDINGS: The composition of the gut microbiome is profoundly distorted during sepsis, with a loss of commensal bacteria and an overgrowth of potential pathogenic micro-organisms. These alterations also extend to nonbacterial intestinal inhabitants. Disruptions of these intestinal communities are associated with both an increased susceptibility to develop sepsis, as well as a higher risk of adverse outcomes. Preclinical studies have characterized the effects of several microbiota-derived metabolites (such as D-lactate, butyrate, and deoxycholic acid) on enhancing the host immune response during critical illness. Microbiota-targeted therapies (e.g. probiotics or fecal microbiota transplantation) might be of benefit, but can also be associated with increased risks of bloodstream infections.<br><br>SUMMARY: Emerging evidence display an important role of gut micro-organisms (including bacteria, fungi, eukaryotic viruses, and bacteriophages) and their derived metabolites in both the susceptibility to, as well as outcomes of sepsis. Despite recent progress in the mechanistic understanding of microbiota-mediated protection, clinical breakthroughs in the development of microbiota-based prognostic tools or therapies are thus far lacking in the field of sepsis.}, }
@article {pmid34419930, year = {2021}, author = {Bjerrum, JT and Wang, YL and Seidelin, JB and Nielsen, OH}, title = {IBD metabonomics predicts phenotype, disease course, and treatment response.}, journal = {EBioMedicine}, volume = {71}, number = {}, pages = {103551}, pmid = {34419930}, issn = {2352-3964}, mesh = {Animals ; Biomarkers/metabolism ; Humans ; Inflammatory Bowel Diseases/*metabolism/pathology/therapy ; *Metabolome ; Phenotype ; }, abstract = {Metabonomics in inflammatory bowel disease (IBD) characterizes the effector molecules of biological systems and thus aims to describe the molecular phenotype, generate insight into the pathology, and predict disease course and response to treatment. Nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and integrated NMR and MS platforms coupled with multivariate analyses have been applied to create such metabolic profiles. Recent advances have identified quiescent ulcerative colitis as a distinct molecular phenotype and demonstrated metabonomics as a promising clinical tool for predicting relapse and response to treatment with biologics as well as fecal microbiome transplantation, thus facilitating much needed precision medicine. However, understanding this complex research field and how it translates into clinical settings is a challenge. This review aims to describe the current workflow, analytical strategies, and associated bioinformatics, and translate current IBD metabonomic knowledge into new potential clinically applicable treatment strategies, and outline future key translational perspectives.}, }
@article {pmid34419770, year = {2021}, author = {Cheraghmakani, H and Rezai, MS and Valadan, R and Rahimzadeh, G and Moradi, M and Jahanfekr, V and Moosazadeh, M and Tabrizi, N}, title = {Ciprofloxacin for treatment of drug-resistant epilepsy.}, journal = {Epilepsy research}, volume = {176}, number = {}, pages = {106742}, doi = {10.1016/j.eplepsyres.2021.106742}, pmid = {34419770}, issn = {1872-6844}, mesh = {Adult ; Anticonvulsants/therapeutic use ; Ciprofloxacin/therapeutic use ; *Drug Resistant Epilepsy/drug therapy ; *Epilepsy, Generalized/drug therapy ; Humans ; Prospective Studies ; Treatment Outcome ; }, abstract = {PURPOSE: To investigate the efficacy of short-term treatment with ciprofloxacin in alteration of gut microbiota pattern and reduction of seizure frequency in adult patients with drug-resistant epilepsy.<br><br>METHODS: In a prospective study, we investigated the effect of a 5-day course of treatment with ciprofloxacin on gut microbiota pattern and seizure frequency of 23 adults with drug-resistant epilepsy. Fecal samples were collected before and after treatment and were analyzed for microbial load and species. Changes in seizure frequency were registered for 12 weeks. Responders were defined as patients who experienced &#x2265;50 % seizure reduction in comparison to baseline. Outcome measures were specified as alteration in fecal microbial burden in days 5-7 and responder rate in 4th and 12th weeks.<br><br>RESULTS: The mean baseline frequency of seizures was5.6 &#xb1;7.7 per week. All patients were on polytherapy with a mean of 3 &#xb1; 1.2 anti-seizure medications. Microbial analysis showed a considerable increase in Bacteroidetes/Firmicutes ratio after treatment. Seizure frequency significantly decreased at the end of first week and the therapeutic effect continued to week 12 (P < 0.001). The responder rate at 4th and 12th weeks were 69.6 % and 73.9 % respectively with a more prominent response in patients with symptomatic generalized epilepsy (P:0.06).<br><br>CONCLUSION: Alteration of abnormal gut microbiota pattern by methods such as short-course antibiotic therapy, prescription of probiotics and fecal microbiota transplant might be effective in treatment of drug-resistant epilepsy.}, }
@article {pmid34416751, year = {2021}, author = {Cao, M and Peng, Y and Lu, Y and Zou, Z and Chen, J and Bottino, R and Knoll, M and Zhang, H and Lin, S and Pu, Z and Sun, L and Fang, Z and Qiu, C and Dai, Y and Cai, Z and Mou, L}, title = {Controls of Hyperglycemia Improves Dysregulated Microbiota in Diabetic Mice.}, journal = {Transplantation}, volume = {105}, number = {9}, pages = {1980-1988}, pmid = {34416751}, issn = {1534-6080}, mesh = {Animals ; Bacteria/classification/genetics/*growth &amp; development ; Biomarkers/blood ; Blood Glucose/*drug effects/metabolism ; Diabetes Mellitus, Experimental/blood/chemically induced/microbiology/*therapy ; Diabetes Mellitus, Type 1/blood/chemically induced/microbiology/*therapy ; Dysbiosis ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Glycemic Control ; Hypoglycemic Agents/*pharmacology ; Insulin/*pharmacology ; Islets of Langerhans Transplantation ; Male ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Ribotyping ; Streptozocin ; Tissue Culture Techniques ; Mice ; }, abstract = {BACKGROUND: Type 1 diabetes (T1DM) is a chronic autoimmune disease characterized by T-cell-mediated destruction of insulin-producing beta cells. Evidence shows that patients with T1DM and mice used in specific diabetic models both exhibit changes in their intestinal microbiota and dysregulated microbiota contributes to the pathogenesis of T1DM. Islet transplantation (Tx) is poised to play an important role in the treatment of T1DM. However, whether treatment of T1DM with islet Tx can rescue dysregulated microbiota remains unclear.<br><br>METHODS: In this study, we induced diabetic C57BL/6 mice with streptozotocin. Then treatment with either insulin administration, or homogenic or allogenic islet Tx was performed to the diabetic mice. Total DNA was isolated from fecal pellets and high-throughput 16S rRNA sequencing was used to investigate intestinal microbiota composition.<br><br>RESULTS: The overall microbial diversity was comparable between control (nonstreptozotocin treated) and diabetic mice. Our results showed the ratio of the Bacteroidetes: Firmicutes between nondiabetic and diabetic mice was significant different. Treatment with islet Tx or insulin partially corrects the dysregulated bacterial composition. At the genus level, Bacteroides, Odoribacter, and Alistipes were associated with the progression and treatment efficacy of the disease, which may be used as a biomarker to predict curative effect of treatment for patients with T1DM.<br><br>CONCLUSIONS: Collectively, our results indicate that diabetic mice show changed microbiota composition and that treatment with insulin and islet Tx can partially correct the dysregulated microbiota.}, }
@article {pmid34416387, year = {2021}, author = {An, L and Wuri, J and Zheng, Z and Li, W and Yan, T}, title = {Microbiota modulate Doxorubicin induced cardiotoxicity.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {166}, number = {}, pages = {105977}, doi = {10.1016/j.ejps.2021.105977}, pmid = {34416387}, issn = {1879-0720}, mesh = {Animals ; Cardiotoxicity ; Doxorubicin/toxicity ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Stroke Volume ; Ventricular Function, Left ; }, abstract = {Chemotherapy has several adverse effects to patients, some of which are life-threatening. We hypothesized that Doxorubicin induced microbiome imbalance and intestinal damage may contribute to Doxorubicin induced cardiac dysfunction. Male adult (2-3 months) C57BL/6 mice were administered 3 mg/kg, 5 mg/kg, 7.5 mg/kg,15 mg/kg, 20 mg/kg doses of Doxorubicin. Echocardiography was performed at 7 and 14 days after Doxorubicin administration. 16S rRNA amplicon sequencing was used to characterize microbiome changes. Fecal microbiota transplantation (FMT) was performed to evaluate the role of the microbiota on Doxorubicin induced cardiac dysfunction. Doxorubicin dose dependently increases mortality rate and induces cardiac dysfunction. 5 mg/kg-Doxorubicin significantly induces decreased left ventricular ejection fraction (LVEF) and fraction shortening (FS) as well as increased cardiac fibrosis, inflammation and oxidative stress respond without increasing mortality. 5 mg/kg-Doxorubicin induces significant decreased colorectum length, increased loss of goblet cells, numbers of ulcers and infiltration of lymphocyte clusters and decreased tight junction protein ZO-1, as well as increased plasma endotoxin level measured by ELISA assay. 16S rRNA microbiota analysis shows that Doxorubicin-induced microbiota dysbiosis with decreased community richness compared with normal control mice. FMT to Doxorubicin-5 mg treated mice significantly improved cardiac function by increasing LVEF and FS as well as decreased perivascular and interstitial fibrosis; increased colorectum length, decreased the loss of goblet cells,infiltration of lymphocyte clusters,the number of ulcers and plasma endotoxin level; improved microbiota composition, function and diversity with increased abundance of Alloprevotella, Prevotellaceae_UCG-001 and Rikenellaceae_RC9_gut_group. We find that normal fecal transplantation improves cardiac function, decreases gut damage and alter microbiota composition induced by Doxorubicin. The microbiota appears to contribute to heart-gut interaction.}, }
@article {pmid34415656, year = {2022}, author = {Chen, B and Huang, H and Pan, CQ}, title = {The role of gut microbiota in hepatitis B disease progression and treatment.}, journal = {Journal of viral hepatitis}, volume = {29}, number = {2}, pages = {94-106}, doi = {10.1111/jvh.13595}, pmid = {34415656}, issn = {1365-2893}, mesh = {Animals ; Disease Progression ; Dysbiosis/therapy ; *Gastrointestinal Microbiome ; *Hepatitis B ; *Hepatitis B, Chronic/therapy ; Mice ; }, abstract = {Current therapeutic interventions can only suppress hepatitis B virus (HBV) replication or reduce complications without a cure. Therefore, further development of new treatment methods is critical for the global eradication of HBV. Accumulating evidence suggests that the liver and gut share an interconnected relationship referred to as the 'Gut-Liver Axis', where exchanges happen bi-directionally. The gut itself is the host to a unique microbiota profile which has metabolic, immunological, neurological and nutritional functions. Gut microbiota is not only constantly intersecting with the liver but also associated with hepatic injury when dysbiosis occurs. In recent years, there has been increased interest in gut microbiota and its implications on liver disease treatment. Progress has been made in understanding the complex relationship between chronic hepatitis B (CHB) and gut microbiota. New investigative techniques such as colony-free sequencing enabled new perspectives into this field. Mouse models and human studies revealed that HBV infection is associated with significant alteration of gut microbiota, which differ depending on the stage of CHB disease progression. Different mechanisms of the hepatic injury from gut microbiota dysbiosis have also been proposed based on findings of increased intestinal permeability to toxins, disruption of normal bacterial metabolism, and colonization of the gut by oral microbiota. New treatment methods targeting gut microbiota in CHB, such as probiotics and faecal microbiota transplant, have also gained promising results in recent years. The current review recapitulated the most recent investigations into the relationship between gut microbiota and CHB to provide research directions towards the new therapeutic target of CHB.}, }
@article {pmid34410652, year = {2021}, author = {Zhu, Z and Kaiser, T and Staley, C}, title = {Antibiotic Conditioning and Single Gavage Allows Stable Engraftment of Human Microbiota in Mice.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2327}, number = {}, pages = {281-291}, pmid = {34410652}, issn = {1940-6029}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces ; Humans ; Mice ; Mice, Inbred C57BL ; *Microbiota ; }, abstract = {Mice transplanted with human microbiota are essential tools for studying the role of microbiota in health and disease, striving for the development of microbiota-modulating therapeutics. Traditionally, germ-free mice have been the principal option for establishing human microbiota-associated (HMA) mouse models, leading to significant insights into the composition and function of the human microbiota. However, there are limitations in using germ-free mice as recipients of human microbiota, including considerable resource allocation to establish and maintain the model and incomplete development of their immune system and physiological functions. Thus, antibiotic-treated, non-germ-free mice have been developed as an alternative to satisfy the growing demand for an accessible HMA mouse model. Several methods have been described for creating "humanized" mice. These protocols vary in their key components, mainly antibiotic conditioning and frequency of oral gavage. To address this practical challenge and formulate a simple and repeatable protocol, we established a HMA mouse model with antibiotic-treated conventional and specific-pathogen free (SPF) C57BL/6J mice, revealing that a single oral gavage allows stable engraftment of the human microbiota. In this chapter, we present our simple protocol for antibiotic conditioning to prepare mice for stable engraftment of human gut microbiota.}, }
@article {pmid34409064, year = {2021}, author = {Yu, X and Zuo, T}, title = {Editorial: Food Additives, Cooking and Processing: Impact on the Microbiome.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {731040}, pmid = {34409064}, issn = {2296-861X}, }
@article {pmid34408774, year = {2021}, author = {Boyer, O and Butler-Browne, G and Chinoy, H and Cossu, G and Galli, F and Lilleker, JB and Magli, A and Mouly, V and Perlingeiro, RCR and Previtali, SC and Sampaolesi, M and Smeets, H and Schoewel-Wolf, V and Spuler, S and Torrente, Y and Van Tienen, F and , }, title = {Myogenic Cell Transplantation in Genetic and Acquired Diseases of Skeletal Muscle.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {702547}, pmid = {34408774}, issn = {1664-8021}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/P016006/1/MRC_/Medical Research Council/United Kingdom ; MR/S015116/1/MRC_/Medical Research Council/United Kingdom ; R01 AR071439/AR/NIAMS NIH HHS/United States ; }, abstract = {This article will review myogenic cell transplantation for congenital and acquired diseases of skeletal muscle. There are already a number of excellent reviews on this topic, but they are mostly focused on a specific disease, muscular dystrophies and in particular Duchenne Muscular Dystrophy. There are also recent reviews on cell transplantation for inflammatory myopathies, volumetric muscle loss (VML) (this usually with biomaterials), sarcopenia and sphincter incontinence, mainly urinary but also fecal. We believe it would be useful at this stage, to compare the same strategy as adopted in all these different diseases, in order to outline similarities and differences in cell source, pre-clinical models, administration route, and outcome measures. This in turn may help to understand which common or disease-specific problems have so far limited clinical success of cell transplantation in this area, especially when compared to other fields, such as epithelial cell transplantation. We also hope that this may be useful to people outside the field to get a comprehensive view in a single review. As for any cell transplantation procedure, the choice between autologous and heterologous cells is dictated by a number of criteria, such as cell availability, possibility of in vitro expansion to reach the number required, need for genetic correction for many but not necessarily all muscular dystrophies, and immune reaction, mainly to a heterologous, even if HLA-matched cells and, to a minor extent, to the therapeutic gene product, a possible antigen for the patient. Finally, induced pluripotent stem cell derivatives, that have entered clinical experimentation for other diseases, may in the future offer a bank of immune-privileged cells, available for all patients and after a genetic correction for muscular dystrophies and other myopathies.}, }
@article {pmid34408753, year = {2021}, author = {Varricchi, G and Poto, R and Ianiro, G and Punziano, A and Marone, G and Gasbarrini, A and Spadaro, G}, title = {Gut Microbiome and Common Variable Immunodeficiency: Few Certainties and Many Outstanding Questions.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {712915}, pmid = {34408753}, issn = {1664-3224}, mesh = {Animals ; Antigens, CD19/genetics/immunology/metabolism ; Biomarkers ; Common Variable Immunodeficiency/diagnosis/*etiology/metabolism/therapy ; Diet Therapy ; Disease Management ; *Disease Susceptibility/immunology ; Dysbiosis ; Fecal Microbiota Transplantation ; Feedback, Physiological ; *Gastrointestinal Microbiome/immunology ; Humans ; Immunity, Mucosal ; Inflammation/diagnosis/etiology ; Intestinal Mucosa/immunology/metabolism/microbiology ; Neoplasms/etiology ; Organ Specificity/genetics/immunology ; Risk ; }, abstract = {Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody immunodeficiency, characterized by reduced serum levels of IgG, IgA, and/or IgM. The vast majority of CVID patients have polygenic inheritance. Immune dysfunction in CVID can frequently involve the gastrointestinal tract and lung. Few studies have started to investigate the gut microbiota profile in CVID patients. Overall, the results suggest that in CVID patients there is a reduction of alpha and beta diversity compared to controls. In addition, these patients can exhibit increased plasma levels of lipopolysaccharide (LPS) and markers (sCD14 and sCD25) of systemic immune cell activation. CVID patients with enteropathy exhibit decreased IgA expression in duodenal tissue. Mouse models for CVID unsatisfactorily recapitulate the polygenic causes of human CVID. The molecular pathways by which gut microbiota contribute to systemic inflammation and possibly tumorigenesis in CVID patients remain poorly understood. Several fundamental questions concerning the relationships between gut microbiota and the development of chronic inflammatory conditions, autoimmune disorders or cancer in CVID patients remain unanswered. Moreover, it is unknown whether it is possible to modify the microbiome and the outcome of CVID patients through specific therapeutic interventions.}, }
@article {pmid34403877, year = {2021}, author = {Chen, L and Kan, J and Zheng, N and Li, B and Hong, Y and Yan, J and Tao, X and Wu, G and Ma, J and Zhu, W and Sheng, L and Chen, L and Li, B and Zhong, J and Du, J and Li, H}, title = {A botanical dietary supplement from white peony and licorice attenuates nonalcoholic fatty liver disease by modulating gut microbiota and reducing inflammation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {91}, number = {}, pages = {153693}, doi = {10.1016/j.phymed.2021.153693}, pmid = {34403877}, issn = {1618-095X}, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Dietary Supplements ; *Gastrointestinal Microbiome/drug effects ; *Glycyrrhiza/chemistry ; Inflammation/drug therapy ; Liver ; Mice ; Mice, Inbred C57BL ; *Non-alcoholic Fatty Liver Disease/drug therapy ; *Paeonia/chemistry ; *Plant Extracts/pharmacology ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related metabolic disease that is highly associated with gut dysbiosis and inflammation. A botanical dietary supplement, mainly containing an herbal pair of white peony root and licorice as well as grape seeds and broccoli extracts (WLT), exerts auxiliary protection against chemical liver injury. However, it is unclear whether WLT protects against the development of NAFLD induced by a high energy diet.<br><br>PURPOSE: To investigate the protective role of WLT against NAFLD development induced by a high-fat and high-sucrose (HFHS) diet and its mechanism of action.<br><br>METHODS: We investigated the anti-NAFLD effects of WLT on a HFHS diet-induced NAFLD C57BL/6J mouse model by detecting the hepatic triglyceride (TG) level, performing histological examination of the liver tissue, and evaluating glucose tolerance and systemic inflammation. Then, we analyzed the impact of WLT on gut microbiota by 16S rRNA gene sequencing, followed by fecal microbiota transplantation. Furthermore, we performed hepatic transcriptomic analysis of mice with or without WLT treatment using the RNA sequencing approach.<br><br>RESULTS: Our results showed that WLT supplement attenuated body weight gain, hepatic steatosis, glucose tolerance, and systemic inflammation in HFHS-fed mice. Moreover, WLT supplement altered the composition of gut microbiota, which contributed at least in part, to the anti-NAFLD effect. Meanwhile, WLT improved the intestinal integrity and comprehensively modulated the expression of hepatic genes in HFHS mice, particularly reducing the expression of genes in the toll-like receptor-mediated inflammatory pathway.<br><br>CONCLUSION: WLT is protective against NAFLD formation induced by an HFHS diet, and its effect is associated with the modulation of gut microbiota and inflammation, highlighting the potential of WLT to reduce the risk of metabolic disorders as a functional dietary supplement.}, }
@article {pmid34403381, year = {2022}, author = {Yao, ZW and Yang, X and Zhao, BC and Deng, F and Jiang, YM and Pan, WY and Chen, XD and Zhou, BW and Zhang, WJ and Hu, JJ and Zhu, L and Liu, KX}, title = {Predictive and Preventive Potential of Preoperative Gut Microbiota in Chronic Postoperative Pain in Breast Cancer Survivors.}, journal = {Anesthesia and analgesia}, volume = {134}, number = {4}, pages = {699-709}, doi = {10.1213/ANE.0000000000005713}, pmid = {34403381}, issn = {1526-7598}, mesh = {Animals ; *Breast Neoplasms/surgery ; *Cancer Survivors ; Case-Control Studies ; Female ; *Gastrointestinal Microbiome ; Humans ; Hyperalgesia ; Mice ; Models, Statistical ; Pain, Postoperative/diagnosis/etiology/prevention &amp; control ; Peroxisome Proliferator-Activated Receptors ; Prognosis ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Evidence suggests a potential relationship between gut microbiota and chronic postoperative pain (CPP). This study aimed to explore the predictive and preventive potential of preoperative gut microbiota in CPP in breast cancer survivors.<br><br>METHODS: In the clinical experiments, we designed a nested case-control study to compared preoperative gut microbiota of breast cancer survivors with and without CPP using 16s rRNA sequencing. The primary outcome was clinically meaningful pain in or around the operative area 3 months after surgery. Logistic prediction models based on previously identified risk factors for CPP in breast cancer survivors were tested with and without differential bacteria to evaluate the model's potential for improvement with the addition of gut microbiota information. In the animal experiments, preoperative fecal microbiota was transplanted from patients with and without CPP to mice, and a spared nerve injury (SNI) model was used to mimic neuropathic pain in CPP. Mechanical hyperalgesia and the expression of markers of spinal microglia and peroxisome proliferator-activated receptor-&#x3b3; (PPAR-&#x3b3;) were assessed.<br><br>RESULTS: Sixty-six CPP patients and 66 matched controls were analyzed. Preoperative gut microbiota composition was significantly different in the 2 groups at phylus, family, and genera levels. The discrimination of the clinical prediction model (determined by area under the receiver operating characteristic curve) improved by 0.039 and 0.099 after the involvement of differential gut microbiota at the family and genus levels, respectively. After fecal microbiota transplantation (FMT), "CPP microbiota" recipient mice exhibited significantly increased mechanical hyperalgesia and decreased expression of Ppar-&#x3b3; and arginase-1 (Arg-1) in the spinal cord.<br><br>CONCLUSIONS: Preoperative gut microbiota has the potential to predict and prevent the development of CPP and plays a causal role in its development via the PPAR-&#x3b3;-microglia pathway in the spinal cord. Thus, it could be targeted to develop a prevention strategy for CPP in breast cancer survivors.}, }
@article {pmid34402648, year = {2021}, author = {Olekhnovich, EI and Ivanov, AB and Ulyantsev, VI and Ilina, EN}, title = {Separation of Donor and Recipient Microbial Diversity Allows Determination of Taxonomic and Functional Features of Gut Microbiota Restructuring following Fecal Transplantation.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0081121}, pmid = {34402648}, issn = {2379-5077}, abstract = {Fecal microbiota transplantation (FMT) is currently used in medicine to treat recurrent clostridial colitis and other intestinal diseases. However, neither the therapeutic mechanism of FMT nor the mechanism that allows the donor bacteria to colonize the intestine of the recipient has yet been clearly described. From a biological point of view, FMT can be considered a useful model for studying the ecology of host-associated microbial communities. FMT experiments can shed light on the relationship features between the host and its gut microbiota. This creates the need for experimentation with approaches to metagenomic data analysis which may be useful for the interpretation of observed biological phenomena. Here, the recipient intestine colonization analysis tool (RECAST) novel computational approach is presented, which is based on the metagenomic read sorting process per their origin in the recipient's post-FMT stool metagenome. Using the RECAST algorithm, taxonomic/functional annotation, and machine learning approaches, the metagenomes from three FMT studies, including healthy volunteers, patients with clostridial colitis, and patients with metabolic syndrome, were analyzed. Using our computational pipeline, the donor-derived and recipient-derived microbes which formed the recipient post-FMT stool metagenomes (successful microbes) were identified. Their presence is well explained by a higher relative abundance in donor/pre-FMT recipient metagenomes or other metagenomes from the human population. In addition, successful microbes are enriched with gene groups potentially related to antibiotic resistance, including antimicrobial peptides. Interestingly, the observed reorganization features are universal and independent of the disease. IMPORTANCE We assumed that the enrichment of successful gut microbes by lantibiotic/antibiotic resistance genes can be related to gut microbiota colonization resistance by third-party microbe phenomena and resistance to bacterium-derived or host-derived antimicrobial substances. According to this assumption, competition between the donor-derived and recipient-derived microbes as well as host immunity may play a key role in the FMT-related colonization and redistribution of recipient gut microbiota structure.}, }
@article {pmid34400407, year = {2021}, author = {Derosa, L and Routy, B and Desilets, A and Daillère, R and Terrisse, S and Kroemer, G and Zitvogel, L}, title = {Microbiota-Centered Interventions: The Next Breakthrough in Immuno-Oncology?.}, journal = {Cancer discovery}, volume = {11}, number = {10}, pages = {2396-2412}, doi = {10.1158/2159-8290.CD-21-0236}, pmid = {34400407}, issn = {2159-8290}, mesh = {*Gastrointestinal Microbiome ; Humans ; Immunotherapy/*trends ; *Microbiota ; *Neoplasms ; }, abstract = {The cancer-immune dialogue subject to immuno-oncological intervention is profoundly influenced by microenvironmental factors. Indeed, the mucosal microbiota-and more specifically, the intestinal ecosystem-influences the tone of anticancer immune responses and the clinical benefit of immunotherapy. Antibiotics blunt the efficacy of immune checkpoint inhibitors (ICI), and fecal microbial transplantation may restore responsiveness of ICI-resistant melanoma. Here, we review the yin and yang of intestinal bacteria at the crossroads between the intestinal barrier, metabolism, and local or systemic immune responses during anticancer therapies. We discuss diagnostic tools to identify gut dysbiosis and the future prospects of microbiota-based therapeutic interventions. SIGNIFICANCE: Given the recent proof of concept of the potential efficacy of fecal microbial transplantation in patients with melanoma primarily resistant to PD-1 blockade, it is timely to discuss how and why antibiotics compromise the efficacy of cancer immunotherapy, describe the balance between beneficial and harmful microbial species in play during therapies, and introduce the potential for microbiota-centered interventions for the future of immuno-oncology.}, }
@article {pmid34398717, year = {2021}, author = {Saul, S and Fuessel, J and Runde, J}, title = {Pediatric Digestive Health and the Gut Microbiome: Existing Therapies and a Look to the Future.}, journal = {Pediatric annals}, volume = {50}, number = {8}, pages = {e336-e342}, doi = {10.3928/19382359-20210720-01}, pmid = {34398717}, issn = {1938-2359}, mesh = {Child ; Dysbiosis/therapy ; Ecosystem ; *Gastrointestinal Microbiome ; Helicobacter Infections ; Helicobacter pylori ; Humans ; *Probiotics/therapeutic use ; }, abstract = {The human gut is host to trillions of microbes that from birth begin interacting with our immune system. Over time this relationship is thought to shape critical aspects of human function such as metabolism, brain development, immune response, and overall gut health. Recent advances in technology have allowed us to begin understanding this complex relationship and have demonstrated that microbes within the gut ecosystem can be influenced by a variety of factors including mode of delivery, diet, and medication exposure, all of which can impact host health in either positive or detrimental ways. Perturbations of gut homeostasis have been implicated in many forms of digestive disease such as inflammatory bowel disease, irritable bowel syndrome, Helicobacter pylori infection, and even in cases of antibiotic-associated diarrhea. As such, researchers have sought methods to either restore gut homeostasis or prevent dysregulation of the gut community, also known as dysbiosis, through an emerging field known as microbial therapeutics. Examples of existing modalities are reviewed here such as prebiotics, probiotics, fecal microbial transplantation, and dietary therapy. As these therapies become further substantiated through research and increasingly desired by patients and their families, there is a need for providers caring for children to familiarize themselves with the existing data and indications for use. As we look to the future, machine-learning algorithms and more readily available next-generation sequencing of fecal samples may allow us to harness data from a person's gut microbiota to predict response to a particular intervention and tailor therapeutic options with an aim toward precision medicine. [Pediatr Ann. 2021;50(8):e336-e342.].}, }
@article {pmid34397627, year = {2021}, author = {Konopelski, P and Konop, M and Perlejewski, K and Bukowska-Osko, I and Radkowski, M and Onyszkiewicz, M and Jaworska, K and Mogilnicka, I and Samborowska, E and Ufnal, M}, title = {Genetically determined hypertensive phenotype affects gut microbiota composition, but not vice versa.}, journal = {Journal of hypertension}, volume = {39}, number = {9}, pages = {1790-1799}, doi = {10.1097/HJH.0000000000002864}, pmid = {34397627}, issn = {1473-5598}, mesh = {Animals ; Blood Pressure ; *Gastrointestinal Microbiome ; *Hypertension/genetics ; Phenotype ; Rats ; Rats, Inbred SHR ; }, abstract = {OBJECTIVES: Research suggests reciprocal crosstalk between the host and gut bacteria. This study evaluated the interaction between gut microbiota and arterial blood pressure (BP) in rats.<br><br>METHODS: Continuous telemetry recordings of BP were started in 7-week-old normotensive Wistar--Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Two weeks later, half of the WKY and SHR were subjected to cross-transplantation of fecal matter, with stools harvested from either WKY or SHR and BP measurements until the age of 14&#x200a;weeks. The composition of gut bacteria was assessed through analysis of the bacterial 16S ribosomal RNA gene sequence. The concentration of microbiota-derived metabolites was evaluated using HPLC-MS.<br><br>RESULTS: There was a significant difference between WKY and SHR in the composition of gut bacteria at the start and end of the study. This was accompanied by significant histological differences in the colon. SHR, but not WKY, showed a gradual increase in BP throughout the experiment. For both WKY and SHR, there was no significant difference in BP or metabolic parameters between animals receiving fecal transplantation from either SHR or WKY.<br><br>CONCLUSION: Genetically induced hypertension in SHR is associated with alterations in the composition of gut bacteria and histological morphology of the colon. An inter-strain fecal transplant does not affect BP and does not produce long-term changes in gut bacteria composition. We propose that the impact of the host genotype and/or phenotype on the gut bacteria may be greater than the impact of the gut bacteria on the host BP.}, }
@article {pmid34395484, year = {2021}, author = {Cui, J and Lin, Z and Tian, H and Yang, B and Zhao, D and Ye, C and Li, N and Qin, H and Chen, Q}, title = {Long-Term Follow-Up Results of Fecal Microbiota Transplantation for Irritable Bowel Syndrome: A Single-Center, Retrospective Study.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {710452}, pmid = {34395484}, issn = {2296-858X}, abstract = {Objective: This study aimed to investigate the long-term efficacy of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS). Study Methods: In this single-center long-term follow-up study, FMT treatment was administered to patients with moderate to severe IBS (IBS severity scoring system (IBS-SSS) > 175). After 1 year of treatment, it was decided whether to repeat FMT based on IBS-SSS score (IBS-SSS > 175). Baseline characteristics before and after FMT and questionnaires were completed at 1, 3, 6, 12, 24, 36, 48, and 60 months after FMT. The study outcomes included treatment efficacy rates, change of IBS-SSS, IBS-specific quality of life and fatigue, effect on stool frequency, Bristol Stool Scale for IBS-C and IBS-D, and side effects. Results: A total of 227 patients (47.58% IBS-C, 39.21% IBS-D, and 13.22% IBS-M) were recruited (142 females and 85 males with a mean age of 41.89 ± 13.57 years). The efficacy rates were 108 (51.92%), 147 (74.62%), 125 (74.41 %), 88 (71.54%), 78 (75.00%), 65 (73.03%), 45 (61.64%), and 37 (62.71%) at different follow-up time points. The total IBS-SSS score was 321.37 ± 73.89 before FMT, which significantly decreased after 1 month. The IBS-specific quality of life (IBS-QoL) score was 40.24 ± 11.34 before FMT, increased gradually, and was significantly higher at 3 months compared to before FMT. The total Fatigue Assessment Scale (FAS) score was 47 ± 8.64 before FMT and was significantly lower at 3 months. During follow-up, 89 (39.21%) side effects occurred that were alleviated by symptomatic treatment, and no serious adverse events were detected. Conclusion: Based on 60 months of long-term follow-up, the safety and efficacy of FMT for IBS was established. However, as the treatment effect declines over time, periodic and repetitive FMT is required for a sustained effect.}, }
@article {pmid34395308, year = {2021}, author = {Jian, Y and Zhang, D and Liu, M and Wang, Y and Xu, ZX}, title = {The Impact of Gut Microbiota on Radiation-Induced Enteritis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {586392}, pmid = {34395308}, issn = {2235-2988}, mesh = {Dysbiosis ; *Enteritis/etiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestines ; *Probiotics ; }, abstract = {Radiotherapy is an important treatment for abdominal tumors. A critical side effect for this therapy is enteritis. In this review, we aim to summarize recent findings in radiation enteritis, in particular the role of gut microbiota dysbiosis in the development and therapy of the disease. Gut microbiota dysbiosis plays an important role in the occurrence of various diseases, such as radiation enteritis. Abdominal radiation results in changes in the composition of microbiota and reduces its diversity, which is mainly reflected in the decrease of Lactobacillus spp. and Bifidobacterium spp. and increase of Escherichia coli and Staphylococcus spp. Gut microbiota dysbiosis aggravates radiation enteritis, weakens intestinal epithelial barrier function, and promotes inflammatory factor expression. Pathogenic Escherichia coli induce the rearrangement and redistribution of claudin-1, occludin, and ZO-1 in tight junctions, a critical component in intestinal epithelial barrier. In view of the role that microbiome plays in radiation enteritis, we believe that intestinal flora could be a potential biomarker for the disease. Correction of microbiome by application of probiotics, fecal microbiota transplantation (FMT), and antibiotics could be an effective method for the prevention and treatment of radiation-induced enteritis.}, }
@article {pmid34393197, year = {2022}, author = {Lucarini, E and Di Pilato, V and Parisio, C and Micheli, L and Toti, A and Pacini, A and Bartolucci, G and Baldi, S and Niccolai, E and Amedei, A and Rossolini, GM and Nicoletti, C and Cryan, JF and O'Mahony, SM and Ghelardini, C and Di Cesare Mannelli, L}, title = {Visceral sensitivity modulation by faecal microbiota transplantation: the active role of gut bacteria in pain persistence.}, journal = {Pain}, volume = {163}, number = {5}, pages = {861-877}, pmid = {34393197}, issn = {1872-6623}, mesh = {Animals ; Bacteria ; Colon/pathology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Mice ; Rats ; *Visceral Pain/drug therapy ; }, abstract = {Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing postinflammatory visceral pain persistence. Colitis was induced in mice by intrarectally injecting 2,4-dinitrobenzenesulfonic acid (DNBS). The effect of faecal microbiota transplantation from viscerally hypersensitive DNBS-treated and naive donors was evaluated in control rats after an antibiotic-mediated microbiota depletion. Faecal microbiota transplantation from DNBS donors induced a long-lasting visceral hypersensitivity in control rats. Pain threshold trend correlated with major modifications in the composition of gut microbiota and short chain fatty acids. By contrast, no significant alterations of colon histology, permeability, and monoamines levels were detected. Finally, by manipulating the gut microbiota of DNBS-treated animals, a counteraction of persistent visceral pain was achieved. The present results provide novel insights into the relationship between intestinal microbiota and visceral hypersensitivity, highlighting the therapeutic potential of microbiota-targeted interventions.}, }
@article {pmid34392792, year = {2021}, author = {Han, X and Wang, Y and Zhang, P and Zhu, M and Li, L and Mao, X and Sha, X and Li, L}, title = {Kazak faecal microbiota transplantation induces short-chain fatty acids that promote glucagon-like peptide-1 secretion by regulating gut microbiota in db/db mice.}, journal = {Pharmaceutical biology}, volume = {59}, number = {1}, pages = {1077-1087}, pmid = {34392792}, issn = {1744-5116}, mesh = {Animals ; Bacteroides/isolation &amp; purification ; Diabetes Mellitus, Experimental/physiopathology/*therapy ; Diabetes Mellitus, Type 2/physiopathology/*therapy ; Fatty Acids, Volatile/*metabolism ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Glucagon-Like Peptide 1/metabolism ; Glucose Tolerance Test ; Glycolipids/metabolism ; Humans ; Mice ; RNA, Ribosomal, 16S ; Receptors, G-Protein-Coupled/metabolism ; }, abstract = {CONTEXT: Faecal microbiota transplantation (FMT) from Kazak individuals with normal glucose tolerance (KNGT) significantly reduces plasma glycolipid levels in type 2 diabetes mellitus db/db mice. However, the mechanism behind this effect has not been reported.<br><br>OBJECTIVE: To study the mechanism of improved glycolipid disorders in db/db mice by FMT from a KNGT donor.<br><br>MATERIALS AND METHODS: The normal diet group consisted of db/m mice orally administered 0.2&#x2009;mL phosphate buffer saline (PBS) (db/m&#x2009;+&#x2009;PBS). For the db/db&#x2009;+&#x2009;PBS (Vehicle) and db/db&#x2009;+&#x2009;KNGT (FMT intervention group) groups, db/db mice received oral 0.2&#x2009;mL PBS or faecal microorganisms from a KNGT donor, respectively. All mice were treated daily for 0, 6 or 10&#x2009;weeks. Faecal DNA samples were sequenced and quantified using 16S rRNA gene sequencing and RT-qPCR, respectively. Short-chain fatty acid (SCFA) levels in the mouse faeces were determined by gas chromatography. G protein-coupled receptor 43 (GPR43) and glucagon-like peptide-1 (GLP-1) expression levels were determined.<br><br>RESULTS: FMT intervention significantly increased the relative abundance of Bacteroides uniformis (0.038%, p&#x2009;<&#x2009;0.05). Clostridium levels (LogSQ) were increased (p&#x2009;<&#x2009;0.01), while Mucispirillum schaedleri levels (LogSQ) were decreased (p&#x2009;<&#x2009;0.01). Acetate and butyrate levels in the faeces were significantly increased (acetate; butyrate: 22.68&#x2009;&#xb1;&#x2009;1.82&#x2009;mmol/L; 4.13&#x2009;&#xb1;&#x2009;1.09&#x2009;mmol/L, p&#x2009;<&#x2009;0.05). GPR43 mRNA expression and GLP-1 protein expression increased in colon tissue (p&#x2009;<&#x2009;0.05).<br><br>DISCUSSION AND CONCLUSIONS: Mechanistically, FMT-KNGT could improve glycolipid disorders by changing the bacterial composition responsible for producing SCFAs and activating the GPR43/GLP-1 pathway.}, }
@article {pmid34391441, year = {2021}, author = {Han, SK and Kim, JK and Park, HS and Shin, YJ and Kim, DH}, title = {Chaihu-Shugan-San (Shihosogansan) alleviates restraint stress-generated anxiety and depression in mice by regulating NF-κB-mediated BDNF expression through the modulation of gut microbiota.}, journal = {Chinese medicine}, volume = {16}, number = {1}, pages = {77}, pmid = {34391441}, issn = {1749-8546}, support = {2017R1A5A2014768//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: Chaihu-Shugan-San (CSS, named Shihosogansan in Korean), a Chinese traditional medicine, is frequently used to treat anxiety and depression. Psychiatric disorders including depression are associated with gut dysbiosis. Therefore, to comprehend gut microbiota-involved anti-depressive effect of CSS, we examined its effect on restraint stress (RS)-induced depression and gut dysbiosis in mice METHODS: CSS was extracted with water in boiling water bath and freeze-dried. Anxiety and depression was induced in C57BL/6 mice by exposure to RS. Anxiety- and depression-like behaviors were measured in the light/dark transition and elevated plus maze tasks, forced swimming test, and tail suspension test. Biomarkers were assayed by using the enzyme-linked immunosorbent assay and immunoblotting. The gut microbiota composition was analyzed by Illumina iSeq sequencer.<br><br>RESULTS: CSS significantly reduced the RS-induced anxiety- and depression-like behaviors in mice. CSS suppressed the RS-induced activation of NF-&#x3ba;B and expression of interleukin (IL)-6 and increased the RS-suppressed expression of brain-derived neurotrophic factor (BDNF). Furthermore, CSS suppressed the RS-induced IL-6 and corticosterone level in the blood and IL-6 expression and myeloperoxidase activity in the colon. CSS decreased the RS-induced &#x3b3;-Proteobacteria population in gut microbiota, while the RS-suppressed Lactobacillaceae, Prevotellaceae, and AC160630_f populations increased. Fecal transplantation of vehicle-treated control or RS/CSS-treated mice into RS-exposed mice significantly mitigated RS-induced anxity- and depression-like behaviors, suppressed the NF-&#x3ba;B activation in the hippocampus and colon, and reduced the IL-6 and corticosterone levels in the blood. These fecal microbiota transplantations suppressed RS-induced Desulfovibrionaceae and &#x3b3;-Proteobacteria populations and increased RS-suppressed Lactobacillaceae and Prevotellaceae poulation in the gut microbiota.<br><br>CONCLUSIONS: CSS alleviated anxiety and depression by inducing NF-&#x3ba;B-involved BDNF expression through the regulation of gut inflammation and microbiota.}, }
@article {pmid34390364, year = {2021}, author = {Oikarinen, S and Krogvold, L and Edwin, B and Buanes, T and Korsgren, O and Laiho, JE and Oikarinen, M and Ludvigsson, J and Skog, O and Anagandula, M and Frisk, G and Hyöty, H and Dahl-Jørgensen, K}, title = {Characterisation of enterovirus RNA detected in the pancreas and other specimens of live patients with newly diagnosed type 1 diabetes in the DiViD study.}, journal = {Diabetologia}, volume = {64}, number = {11}, pages = {2491-2501}, pmid = {34390364}, issn = {1432-0428}, mesh = {Adult ; Cell Line ; Diabetes Mellitus, Type 1/diagnosis/*virology ; Enterovirus/genetics/*isolation &amp; purification ; Enterovirus Infections/*virology ; Feces/virology ; Female ; Humans ; Islets of Langerhans/*virology ; Male ; RNA, Viral/*genetics ; Real-Time Polymerase Chain Reaction ; Young Adult ; }, abstract = {AIMS/HYPOTHESIS: The Diabetes Virus Detection (DiViD) study is the first study to laparoscopically collect pancreatic tissue and purified pancreatic islets together with duodenal mucosa, serum, peripheral blood mononuclear cells (PBMCs) and stools from six live adult patients (age 24-35 years) with newly diagnosed type 1 diabetes. The presence of enterovirus (EV) in the pancreatic islets of these patients has previously been reported.<br><br>METHODS: In the present study we used reverse transcription quantitative real-time PCR (RT-qPCR) and sequencing to characterise EV genomes present in different tissues to understand the nature of infection in these individuals.<br><br>RESULTS: All six patients were found to be EV-positive by RT-qPCR in at least one of the tested sample types. Four patients were EV-positive in purified islet culture medium, three in PBMCs, one in duodenal biopsy and two in stool, while serum was EV-negative in all individuals. Sequencing the 5' untranslated region of these EVs suggested that all but one belonged to enterovirus B species. One patient was EV-positive in all these sample types except for serum. Sequence analysis revealed that the virus strain present in the isolated islets of this patient was different from the strain found in other sample types. None of the islet-resident viruses could be isolated using EV-permissive cell lines.<br><br>CONCLUSIONS/INTERPRETATION: EV RNA can be frequently detected in various tissues of patients with type 1 diabetes. At least in some patients, the EV strain in the pancreatic islets may represent a slowly replicating persisting virus.}, }
@article {pmid34384521, year = {2021}, author = {Greathouse, KL and Johnson, AJ}, title = {Does caloric restriction prime the microbiome for pathogenic bacteria?.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {8}, pages = {1209-1211}, doi = {10.1016/j.chom.2021.07.009}, pmid = {34384521}, issn = {1934-6069}, mesh = {Animals ; Bacteria/*pathogenicity ; *Caloric Restriction ; Clostridioides difficile ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Mice ; Obesity/microbiology ; Weight Loss ; }, abstract = {A recent study in Nature finds significant shifts in the gut microbiome of post-menopausal women on severe calorie restriction concomitant with weight loss. Microbiota transplantation to germ-free mice display a similar weight loss, along with a bloom in C. difficile, unlocking clues to microbial metabolic alteration in weight loss.}, }
@article {pmid34383708, year = {2021}, author = {Gholam-Mostafaei, FS and Yadegar, A and Asadzadeh Aghdaei, H and Shahrokh, S and Ebrahimi Daryani, N and Zali, MR}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2021.01498}, pmid = {34383708}, issn = {1588-2640}, abstract = {Treatment of recurrent Clostridioides difficile infection (rCDI) has emerged as an important management dilemma particularly in patients with underlying inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been used as a safe and highly effective treatment option for rCDI refractory to standard antibiotic therapies. The aim of this study was to report the efficacy of FMT in Iranian rCDI patients with concurrent IBD. A total of seven consecutive patients with ulcerative colitis (UC) who had experienced 3 episodes of rCDI were enrolled in this study. All patients received at least a single FMT administered during colonoscopy by direct infusion of minimally processed donor stool. Patients were followed for a minimum of 6 months for assessment of treatment efficacy and adverse events (AEs) attributable to FMT. All 7 UC patients (100%) experienced a durable clinical response to a single FMT following 2 months after the procedure. One patient received a second FMT in which a successful resolution of rCDI was ultimately achieved. No serious AEs from FMT were noted. FMT through colonoscopy was a safe, simple and effective alternative treatment approach for rCDI in patients with underlying IBD. However, its use and efficacy should be pursued in long-term prospective controlled trials.}, }
@article {pmid34382991, year = {2021}, author = {Han, J and Wang, Z and Lu, C and Zhou, J and Li, Y and Ming, T and Zhang, Z and Wang, ZJ and Su, X}, title = {The gut microbiota mediates the protective effects of anserine supplementation on hyperuricaemia and associated renal inflammation.}, journal = {Food &amp; function}, volume = {12}, number = {19}, pages = {9030-9042}, doi = {10.1039/d1fo01884a}, pmid = {34382991}, issn = {2042-650X}, mesh = {Animals ; Anserine/administration &amp; dosage/pharmacology/*therapeutic use ; *Dietary Supplements ; Disease Models, Animal ; Feces/microbiology ; Functional Food ; Gastrointestinal Microbiome/drug effects ; Humans ; Hyperuricemia/*drug therapy ; Male ; Mice ; Mice, Inbred ICR ; Phytotherapy ; Uric Acid/blood ; }, abstract = {Hyperuricaemia is a disease associated with elevated serum uric acid content, which has emerged rapidly in recent decades. The drugs used to treat clinical hyperuricaemia have side effects, and their safety is poor. However, anserine is a natural carnosine derivative that shows an anti-hyperuricaemic effect. A previous study demonstrated that anserine inhibits uric acid synthesis and promotes uric acid excretion, but there is no evidence regarding the effect of anserine from the perspective of the gut microbiota. In this study, the anti-hyperuricaemic and anti-inflammatory effects of anserine were explored in a diet-induced hyperuricaemic mouse model. Anserine alleviated hyperuricaemia and renal inflammation phenotypes, inhibited uric acid biosynthesis, promoted uric acid excretion, and inhibited NLRP3 inflammasome and TLR4/MyD88/NF-κB signalling pathway activation. The results showed that the anti-hyperuricaemic effect of anserine was dependent on the gut microbiota in the germ-free mice experiment. Furthermore, anserine treatment reversed gut microbiota dysbiosis, repaired the intestinal epithelial barrier and increased short-chain fatty acid production. Moreover, the anti-hyperuricaemic effect of anserine was transmissible by transplanting the faecal microbiota from anserine-treated mice, indicating that the protective effects were at least partially mediated by the gut microbiota. Thus, we identified a new and safe prebiotic material to alleviate hyperuricaemia and provided ideas for the development of oligopeptides.}, }
@article {pmid34382390, year = {2021}, author = {Zhao, Y and Liu, S and Tang, Y and You, T and Xu, H}, title = {Lactobacillus rhamnosus GG Ameliorated Long-Term Exposure to TiO2 Nanoparticles Induced Microbiota-Mediated Liver and Colon Inflammation and Fructose-Caused Metabolic Abnormality in Metabolism Syndrome Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {34}, pages = {9788-9799}, doi = {10.1021/acs.jafc.1c03301}, pmid = {34382390}, issn = {1520-5118}, mesh = {Animals ; Colon ; Fructose ; Inflammation ; *Lacticaseibacillus rhamnosus ; Liver ; Mice ; *Microbiota ; *Nanoparticles ; *Probiotics ; Titanium ; }, abstract = {A huge number of titanium dioxide nanoparticles (TiO2 NPs) exist in confectionery foods, which is a high-risk factor for development of diet-induced metabolism syndrome (MetS). In this study, we built a high fructose drinking-induced MetS mouse model, and oral intake of 20 mg/kg TiO2 NPs was administered for 8 weeks. Significant pathological changes and inflammatory factors of overproduction were detected in the liver and colon. The 16S rDNA sequencing analysis results indicated that TiO2 NPs evidently and further perturbed the gut microbiota diversity, compositions, and KEGG pathways in MetS mice. Fecal microbiota transplant experiment proved that TiO2 NPs-altered gut microbiota drives liver and colon inflammation damage. More importantly, oral supplementation of Lactobacillus rhamnosus GG (LGG) ameliorated not only the TiO2 NPs-induced inflammation but also the fructose-caused metabolic abnormality. LGG recovered the gut dysbiosis and decreased the abundance of inflammation-related bacteria (Desulfovibrionaceae, Clostridia, and Proteobacteria), thereby protecting against TiO2 NPs-induced severe inflammation damage. Our study suggests the necessity of assessing the toxic effects of foodborne nanoparticles on the chronic disease population and potential usefulness of probiotics as prophylactic and therapeutic.}, }
@article {pmid34381207, year = {2021}, author = {Fremin, BJ and Nicolaou, C and Bhatt, AS}, title = {Simultaneous ribosome profiling of hundreds of microbes from the human microbiome.}, journal = {Nature protocols}, volume = {16}, number = {10}, pages = {4676-4691}, pmid = {34381207}, issn = {1750-2799}, support = {R01 AI148623/AI/NIAID NIH HHS/United States ; U24 AG021886/AG/NIA NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; P50 AG047366/AG/NIA NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; P30 AG047366//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; P30 AG066515/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Ribosomes/metabolism/genetics ; *Feces/microbiology ; *Microbiota/genetics ; Metagenomics/methods ; Metagenome ; Bacteria/genetics/classification ; High-Throughput Nucleotide Sequencing/methods ; Gastrointestinal Microbiome/genetics ; Ribosome Profiling ; }, abstract = {Ribosome profiling enables sequencing of ribosome-bound fragments of RNA, revealing which transcripts are being translated as well as the position of ribosomes along mRNAs. Although ribosome profiling has been applied to cultured bacterial isolates, its application to uncultured, mixed communities has been challenging. We present MetaRibo-Seq, a protocol that enables the application of ribosome profiling directly to the human fecal microbiome. MetaRibo-Seq is a benchmarked method that includes several modifications to existing ribosome profiling protocols, specifically addressing challenges involving fecal sample storage, purity and input requirements. We also provide a computational workflow to quality control and trim reads, de novo assemble a reference metagenome with metagenomic reads, align MetaRibo-Seq reads to the reference, and assess MetaRibo-Seq library quality (https://github.com/bhattlab/bhattlab_workflows/tree/master/metariboseq). This MetaRibo-Seq protocol enables researchers in standard molecular biology laboratories to study translation in the fecal microbiome in ~5 d.}, }
@article {pmid34381040, year = {2021}, author = {Wang, H and Yang, F and Zhang, S and Xin, R and Sun, Y}, title = {Genetic and environmental factors in Alzheimer's and Parkinson's diseases and promising therapeutic intervention via fecal microbiota transplantation.}, journal = {NPJ Parkinson's disease}, volume = {7}, number = {1}, pages = {70}, pmid = {34381040}, issn = {2373-8057}, abstract = {Neurodegenerative diseases are characterized by neuronal impairment and loss of function, and with the major shared histopathological hallmarks of misfolding and aggregation of specific proteins inside or outside cells. Some genetic and environmental factors contribute to the promotion of the development and progression of neurodegenerative diseases. Currently, there are no effective treatments for neurodegenerative diseases. It has been revealed that bidirectional communication exists between the brain and the gut. The gut microbiota is a changeable and experience-dependent ecosystem and can be modified by genetic and environmental factors. The gut microbiota provides potential therapeutic targets that can be regulated as new interventions for neurodegenerative diseases. In this review, we discuss genetic and environmental risk factors for neurodegenerative diseases, summarize the communication among the components of the microbiota-gut-brain axis, and discuss the treatment strategy of fecal microbiota transplantation (FMT). FMT is a promising treatment for neurodegenerative diseases, and restoration of the gut microbiota to a premorbid state is a novel goal for prevention and treatment strategies.}, }
@article {pmid34378656, year = {2021}, author = {Liaqat, I and Ali, NM and Arshad, N and Sajjad, S and Rashid, F and Hanif, U and Ara, C and Ulfat, M and Andleeb, S and Awan, UF and Bibi, A and Mubin, M and Ali, S and Tahir, HM and Ul-Haq, I}, title = {Gut dysbiosis, inflammation and type 2 diabetes in mice using synthetic gut microbiota from diabetic humans.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {83}, number = {}, pages = {e242818}, doi = {10.1590/1519-6984.242818}, pmid = {34378656}, issn = {1678-4375}, mesh = {Animals ; Bacteroides ; Bacteroidetes ; *Diabetes Mellitus, Type 2 ; Diet, High-Fat/adverse effects ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Mice ; Mice, Inbred C57BL ; Prevotella ; RNA, Ribosomal, 16S/genetics ; Ruminococcus ; }, abstract = {The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P<0.05) increase in weight and blood glucose concentration as well as elevated level of inflammatory cytokines (TNF-α, IL-6, and MCP-1) compared to mice receiving CD only. The 16S rRNA gene sequencing of 11 fecal bacteria obtained from three randomly selected animals from each group revealed gut dysbiosis in animals receiving GM. Bacterial strains including Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) and Lactobacillus gasseri (MT152635) were isolated from mice treated with GM+modified diet (HFD/CD) compared to strains Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629) which were isolated from mice receiving CD/HFD. In conclusion, these findings suggest that constitution of GM and diet plays significant role in inflammation leading to onset or/and possibly progression of T2D. .}, }
@article {pmid34376591, year = {2021}, author = {Kurokawa, S}, title = {[The Link Between Gut Microbiota and Cerebral Functions: An Update on the Pathogenesis and Treatment of Functional Gastrointestinal Disorders].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {73}, number = {8}, pages = {857-862}, doi = {10.11477/mf.1416201852}, pmid = {34376591}, issn = {1881-6096}, mesh = {Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; }, abstract = {Recent studies have focused on the mechanism of brain effects on functional gastrointestinal disorders, through dysbiosis of the gut microbiota. Herein, we summarize the known pathogeneses of various functional gastrointestinal disorders relative to the gut microbiota, and discuss future gut microbiota-focused interventions for restoring dysbiosis, including probiotics and fecal microbiota transplantation.}, }
@article {pmid34370175, year = {2021}, author = {Moustafa, SA and Mohamed, S and Dawood, A and Azar, J and Elmorsy, E and Rizk, NAM and Salama, M}, title = {Gut brain axis: an insight into microbiota role in Parkinson's disease.}, journal = {Metabolic brain disease}, volume = {36}, number = {7}, pages = {1545-1557}, pmid = {34370175}, issn = {1573-7365}, mesh = {Anti-Bacterial Agents/therapeutic use ; Brain-Gut Axis/*physiology ; Dysbiosis/complications ; Fatty Acids, Volatile/physiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Lipids/physiology ; Parkinson Disease/drug therapy/*etiology ; Probiotics/therapeutic use ; alpha-Synuclein/physiology ; }, abstract = {Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. It is characterized neuropathologically by the presence of alpha-synuclein containing Lewy Bodies in the substantia nigra of the brain with loss of dopaminergic neurons in the pars compacta of the substantia nigra. The presence of alpha-synuclein aggregates in the substantia nigra and the enteric nervous system (ENS) drew attention to the possibility of a correlation between the gut microbiota and Parkinson's disease. The gut-brain axis is a two-way communication system, which explains how through the vagus nerve, the gut microbiota can affect the central nervous system (CNS), including brain functions related to the ENS, as well as how CNS can alter various gut secretions and immune responses. As a result, this dysbiosis or alteration in gut microbiota can be an early sign of PD with reported changes in short chain fatty acids, bile acids, and lipids. This gave rise to the use of probiotics and faecal microbiota transplantation as alternative approaches to improve the symptoms of patients with PD. The aim of this review is to discuss investigations that have been done to explore the gastrointestinal involvement in Parkinson's disease, the effect of dysbiosis, and potential therapeutic strategies for PD.}, }
@article {pmid34368762, year = {2021}, author = {Puca, P and Petito, V and Laterza, L and Lopetuso, LR and Neri, M and Del Chierico, F and Boskoski, I and Gasbarrini, A and Scaldaferri, F}, title = {Bariatric procedures and microbiota: patient selection and outcome prediction.}, journal = {Therapeutic advances in gastrointestinal endoscopy}, volume = {14}, number = {}, pages = {26317745211014746}, pmid = {34368762}, issn = {2631-7745}, abstract = {Obesity is a major health issue throughout the world and bariatric surgery plays a key role in its management and treatment. The role of microbiota in determining the pathogenesis of obesity has been widely studied, while its role in determining the outcome of bariatric surgery is an emerging issue that will be an outcome in near future studies. Studies on mice first showed the key role of microbiota in determining obesity, highlighting the fat mass increase in mice transplanted with microbiota from fat individuals, as well as the different microbiota composition between mice undergone to low-fat or high-fat diets. This led to characterize the asset of microbiota composition in obesity: increased abundance of Firmicutes, reduced abundance of Bacteroidetes and other taxonomical features. Variations on the composition of gut microbiome have been detected in patients undergone to diet and/or bariatric surgery procedures. Patients undergone to restricting diets showed lower level of trimethylamine N-oxide and other metabolites strictly associated to microbiome, as well as patients treated with bariatric surgery showed, after the procedure, changes in the relative abundance of Bacteroidetes, Firmicutes and other phyla with a role in the pathogenesis of obesity. Eventually, studies have been led about the effects that the modification of microbiota could have on obesity itself, mainly focusing on elements like fecal microbiota transplantation and probiotics such as inulin. This series of studies and considerations represent the first step in order to select patients eligible to bariatric surgery and to predict their outcome.}, }
@article {pmid34368717, year = {2020}, author = {Weinberg, SE and Villedieu, A and Bagdasarian, N and Karah, N and Teare, L and Elamin, WF}, title = {Control and management of multidrug resistant Acinetobacter baumannii: A review of the evidence and proposal of novel approaches.}, journal = {Infection prevention in practice}, volume = {2}, number = {3}, pages = {100077}, pmid = {34368717}, issn = {2590-0889}, abstract = {Hospital-acquired infections are on the rise and are a substantial cause of clinical and financial burden for healthcare systems. While infection control plays a major role in curtailing the spread of outbreak organisms, it is not always successful. One organism of particular concern is Acinetobacter baumannii, due to both its persistence in the hospital setting and its ability to acquire antibiotic resistance. A. baumannii has emerged as a nosocomial pathogen that exhibits high levels of resistance to antibiotics, and remains resilient against traditional cleaning measures with resistance to Colistin increasingly reported. Given the magnitude and costs associated with hospital acquired infections, and the increase in multidrug-resistant organisms, it is worth re-evaluating our current approaches and looking for alternatives or adjuncts to traditional antibiotics therapies. The aims of this review are to look at how this organism is spread within the hospital setting, discuss current treatment modalities, and propose alternative methods of outbreak management.}, }
@article {pmid34367617, year = {2021}, author = {Manzoor, SE and Zaman, S and Whalley, C and Inglis, D and Bosworth, A and Kidd, M and Shabir, S and Quraishi, N and Green, CA and Iqbal, T and Beggs, AD}, title = {Multi-modality detection of SARS-CoV-2 in faecal donor samples for transplantation and in asymptomatic emergency surgical admissions.}, journal = {F1000Research}, volume = {10}, number = {}, pages = {373}, pmid = {34367617}, issn = {2046-1402}, mesh = {*COVID-19 ; Fecal Microbiota Transplantation ; Humans ; RNA, Viral/genetics ; Real-Time Polymerase Chain Reaction ; *SARS-CoV-2 ; }, abstract = {Background: Faecal transplantation is an evidence-based treatment for Clostridioides difficile. Patients infected with SARS-CoV-2 have been shown to shed the virus in stool for up to 33 days, well beyond the average clearance time for upper respiratory tract shedding. We carried out an analytical and clinical validation of reverse-transcriptase quantitative (RT-qPCR) as well as LAMP, LamPORE and droplet digital PCR in the detection of SARS-CoV-2 RNA in stool from donated samples for faecal microbiota transplantation (FMT), spiked samples and asymptomatic inpatients in an acute surgical unit. Methods: Killed SARS-CoV-2 viral lysate and extracted RNA was spiked into donor stool &amp; FMT and a linear dilution series from 10 [-1] to 10 [-5] and tested via RT-qPCR, LAMP, LamPORE and ddPCR against SARS-CoV-2. Patients admitted to the critical care unit with symptomatic SARS-CoV-2 and sequential asymptomatic patients from acute presentation to an acute surgical unit were also tested. Results: In a linear dilution series, detection of the lowest dilution series was found to be 8 copies per microlitre of sample. Spiked lysate samples down to 10 [-2] dilution were detected in FMT samples using RTQPCR, LamPORE and ddPCR and down to 10 [-1] with LAMP. In symptomatic patients 5/12 had detectable SARS-CoV-2 in stool via RT-qPCR and 6/12 via LamPORE, and in 1/97 asymptomatic patients via RT-qPCR. Conclusion: RT-qPCR can be detected in FMT donor samples using RT-qPCR, LamPORE and ddPCR to low levels using validated pathways. As previously demonstrated, nearly half of symptomatic and less than one percent of asymptomatic patients had detectable SARS-CoV-2 in stool.}, }
@article {pmid35757563, year = {2020}, author = {Soto Chervin, C and Gajewski, TF}, title = {Microbiome-based interventions: therapeutic strategies in cancer immunotherapy.}, journal = {Immuno-oncology technology}, volume = {8}, number = {}, pages = {12-20}, pmid = {35757563}, issn = {2590-0188}, support = {T32 CA009566/CA/NCI NIH HHS/United States ; }, abstract = {The composition of the commensal microbiota has recently emerged as a key element influencing the efficacy of cancer treatments. It has become apparent that the interplay between the microbiome and immune system within the host influences the response to immunotherapy, particularly immune checkpoint inhibitor therapy. Identifying the key components of the gut microbiota that influence this response is paramount for designing therapeutic interventions to enhance the response to cancer therapy. This review will discuss strategies being considered to modulate the gut microbiota, including fecal microbiota transplantation, administration of defined bacterial isolates as well as bacterial consortia, supplementation with probiotics, and lifestyle modifications such as dietary changes. Understanding the influence of the complex variables of the human microbiota on the effectiveness of cancer therapy will help drive the clinical design of microbial-based interventions in the field of oncology.}, }
@article {pmid34595408, year = {2019}, author = {Shouval, R and Geva, M and Nagler, A and Youngster, I}, title = {Fecal Microbiota Transplantation for Treatment of Acute Graft-versus-Host Disease.}, journal = {Clinical hematology international}, volume = {1}, number = {1}, pages = {28-35}, pmid = {34595408}, issn = {2590-0048}, abstract = {The growing understanding of the bidirectional relationship between the gastrointestinal (GI) microbiome and the immune system has opened up new avenues for treatment of graft-versus-host disease (GVHD). Fecal microbiota transplantation (FMT) is the transfer of stool from a donor to a recipient who harbors a perturbed GI microbiome resulting in disease. We review the rationale for performing FMT for the treatment of acute GVHD, and summarize data on the safety and efficacy of the procedure among allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Overall, FMT is a promising strategy in treating and preventing HSCT-related complications. However, caution should be exerted as HSCT recipients are highly immunosuppressed and unanticipated infectious adverse events may appear with the increasing application of FMT.}, }
@article {pmid35539874, year = {2018}, author = {Diao, H and Yan, HL and Xiao, Y and Yu, B and Zheng, P and He, J and Yu, J and Mao, XB and Chen, DW}, title = {Modulation of intestine development by fecal microbiota transplantation in suckling pigs.}, journal = {RSC advances}, volume = {8}, number = {16}, pages = {8709-8720}, pmid = {35539874}, issn = {2046-2069}, abstract = {The present study was conducted to investigate the effects of early fecal microbiota transplantation on gut development in sucking piglets. A total of 24 3 day-old DLY sucking piglets (2.11 ± 0.15) kg were randomly divided into four groups (TMP, YMP, RMP and control group (CON)), which were transplanted with intact fecal microbiota of Tibetan pig (TP), Yorkshire pig (YP), Rongchang pig (RP), and without transplantation, respectively. The whole trial lasted for 56 d. The results are as follows: when compared with the YMP and RMP treatments, TMP and CON had a lower diarrhea index (P < 0.05), TMP and CON had higher GLP-2 and ANG4 mRNA abundances in the ileum (P < 0.05), and the TMP had a higher jejunal villus height: crypt depth and a higher colonic GLP-2 mRNA abundance (P < 0.05). Moreover, when compared with the YMP and RMP treatments, TMP had an enhanced DMT1 mRNA abundance in the duodenum (P < 0.05), TMP and CON had a greater lactase activity and a higher DMT1 mRNA abundance in the jejunum (P < 0.05), and CON had a higher γ-GT activity in the jejunum (P < 0.05). The jejunal Ca[2+], Mg[2+]-ATPase activity in TMP was higher than that in CON, and the jejunal Na[+], K[+]-ATPase activity in TMP was higher than that in the other three treatments (P < 0.05). Besides, when compared with the YMP and RMP treatments, TMP had a lower MDA content and a higher MUC1 mRNA abundance in the jejunum (P < 0.05); CON had a higher SOD activity in the jejunum (P < 0.05), whereas TMP and CON had a higher butyric acid concentration in the colon and a lower LPS content in the serum (P < 0.05). Finally, when compared with the TMP treatment, the other three treatments had an enhanced IL-10 mRNA abundance in the colon (P < 0.05), YMP and CON had higher counts of Escherichia coli in the colonic digesta (P < 0.05), and the CON had lower counts of Lactobacillus spp in the cecal and colonic digesta (P < 0.05). These data indicated that early transplantation of the fecal microbiota from the Yorkshire pigs and Rongchang pigs to DLY suckling piglets would destroy the gut microbiota balance and thus damage intestinal health.}, }
@article {pmid34367139, year = {2021}, author = {Qu, Y and Li, X and Xu, F and Zhao, S and Wu, X and Wang, Y and Xie, J}, title = {Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {679897}, pmid = {34367139}, issn = {1664-3224}, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Biomarkers ; Colitis/etiology/*metabolism/pathology/therapy ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects ; Intestinal Mucosa/metabolism/microbiology ; Kaempferols/*pharmacology ; Lipopolysaccharides/adverse effects ; Mice ; NF-kappa B/*metabolism ; Permeability ; RNA, Ribosomal, 16S ; Signal Transduction/*drug effects ; Toll-Like Receptor 4/*metabolism ; }, abstract = {Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)-dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.}, }
@article {pmid34366625, year = {2021}, author = {Torre, P and Aglitti, A and Masarone, M and Persico, M}, title = {Viral hepatitis: Milestones, unresolved issues, and future goals.}, journal = {World journal of gastroenterology}, volume = {27}, number = {28}, pages = {4603-4638}, pmid = {34366625}, issn = {2219-2840}, mesh = {Animals ; Goals ; *Hepatitis B, Chronic ; *Hepatitis E/diagnosis/epidemiology ; *Hepatitis E virus ; Humans ; Zoonoses ; }, abstract = {In this review the current overall knowledge on hepatitis A, B, C, D, and E will be discussed. These diseases are all characterized by liver inflammation but have significant differences in distribution, transmission routes, and outcomes. Hepatitis B virus and hepatitis C virus are transmitted by exposure to infected blood, and in addition to acute infection, they can cause chronic hepatitis, which in turn can evolve into cirrhosis. It is estimated that more than 300 million people suffer from chronic hepatitis B or C worldwide. Hepatitis D virus, which is also transmitted by blood, only affects hepatitis B virus infected people, and this dual infection results in worse liver-related outcomes. Hepatitis A and E spread via the fecal-oral route, which corresponds mainly to the ingestion of food or water contaminated with infected stools. However, in developed countries hepatitis E is predominantly a zoonosis. Although hepatitis A virus and hepatitis E virus are usually responsible for a self-limiting hepatitis, a serious, rarely fatal illness is also possible, and in immunosuppressed patients, such as organ transplant recipients, hepatitis E virus infection can become chronic. The description of goals achieved, unresolved issues, and the latest research on this topic may make it possible to speculate on future scenarios in the world of viral hepatitis.}, }
@article {pmid34365962, year = {2022}, author = {Wang, Y and Dykes, GA}, title = {Direct Modulation of the Gut Microbiota as a Therapeutic Approach for Alzheimer's Disease.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {21}, number = {1}, pages = {14-25}, doi = {10.2174/1871527320666210806165751}, pmid = {34365962}, issn = {1996-3181}, mesh = {Alzheimer Disease/*drug therapy ; Brain/drug effects ; Brain-Gut Axis ; Dysbiosis/drug therapy ; Gastrointestinal Microbiome/*drug effects ; Humans ; Probiotics/*therapeutic use ; }, abstract = {Alzheimer's disease is a neurodegenerative disease characterized by a progressive decline in memory and cognitive functions. It is a multifactorial disease involving a wide range of pathological factors that are not fully understood. As supported by a growing amount of evidence in recent years, gut microbiota plays an important role in the pathogenesis of Alzheimer's disease through the brain-gut-microbiota axis. This suggests that direct modulation of the gut microbiota can be a potential therapeutic target for Alzheimer's disease. This review summarizes recent research findings on the modulation of the gut microbiota by probiotic therapies and faecal microbiota transplantation for controlling the pathologies of Alzheimer's disease. Current limitations and future research directions of this field are also discussed.}, }
@article {pmid34364884, year = {2022}, author = {McCarthy, S and Barrett, M and Kirthi, S and Pellanda, P and Vlckova, K and Tobin, AM and Murphy, M and Shanahan, F and O'Toole, PW}, title = {Altered Skin and Gut Microbiome in Hidradenitis Suppurativa.}, journal = {The Journal of investigative dermatology}, volume = {142}, number = {2}, pages = {459-468.e15}, doi = {10.1016/j.jid.2021.05.036}, pmid = {34364884}, issn = {1523-1747}, mesh = {Adult ; Aged ; Case-Control Studies ; Clostridiales/immunology/isolation &amp; purification ; Extracellular Traps/immunology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Firmicutes/immunology/isolation &amp; purification ; Gastrointestinal Microbiome/*immunology ; Hidradenitis Suppurativa/immunology/*microbiology/pathology/therapy ; Humans ; Male ; Middle Aged ; Skin/immunology/*microbiology/pathology ; Young Adult ; }, abstract = {Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the formation of nodules, abscesses, and fistulae at intertriginous sites. The skin-gut axis is an area of emerging research in inflammatory skin disease and is a potential contributory factor to the pathogenesis of HS. A total of 59 patients with HS provided fecal samples and nasal and skin swabs of affected sites for analysis. A total of 30 healthy controls provided fecal samples, and 20 healthy controls provided nasal and skin swabs. We performed bacterial 16S ribosomal RNA gene amplicon sequencing on total DNA derived from the samples. Microbiome alpha diversity was significantly lower in the fecal, skin, and nasal samples of individuals with HS, which may be secondary to disease biology or related to antibiotic usage. Ruminococcus gnavus was more abundant in the fecal microbiome of individuals with HS, which is also reported in Crohn's disease, suggesting comorbidity due to shared gut microbiota alterations. Finegoldia magna was overabundant in HS skin samples relative to that in the healthy controls. It is possible that local inflammation is driven by F. magna by promoting the formation of neutrophil extracellular traps. These alterations in both the gut and skin microbiome in HS warrant further exploration, and therapeutic strategies, including fecal microbiota transplant or bacteriotherapy, could be of benefit.}, }
@article {pmid34364787, year = {2021}, author = {Sen, P and Molinero-Perez, A and O'Riordan, KJ and McCafferty, CP and O'Halloran, KD and Cryan, JF}, title = {Microbiota and sleep: awakening the gut feeling.}, journal = {Trends in molecular medicine}, volume = {27}, number = {10}, pages = {935-945}, doi = {10.1016/j.molmed.2021.07.004}, pmid = {34364787}, issn = {1471-499X}, mesh = {Brain/pathology ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; Prebiotics ; *Probiotics ; Sleep ; }, abstract = {Various lifestyle and environmental factors are known to influence sleep. Increasingly, evidence points to a role for the microbiota in regulating brain and behaviour. This article explores how the microbiota-gut-brain axis affects sleep directly and indirectly. We summarize the possible molecular mechanisms underlying sleep-microbiome interactions and discuss how various factors interact with the gut microbiota to influence sleep. Furthermore, we present the current evidence of alterations of the microbiota-gut-brain axis in various sleep disorders and pathologies where comorbid sleep disturbances are common. Since manipulating the gut microbiota could potentially improve sleep, we outline ways in which this can be achieved.}, }
@article {pmid34364710, year = {2021}, author = {Kanangat, S and Skaljic, I}, title = {Microbiome analysis, the immune response and transplantation in the era of next generation sequencing.}, journal = {Human immunology}, volume = {82}, number = {11}, pages = {883-901}, doi = {10.1016/j.humimm.2021.07.009}, pmid = {34364710}, issn = {1879-1166}, mesh = {Computational Biology ; Dysbiosis/*diagnosis/immunology/microbiology ; Graft Rejection/immunology/prevention &amp; control ; HLA Antigens/genetics ; *High-Throughput Nucleotide Sequencing ; Histocompatibility Testing/methods ; Host Microbial Interactions/genetics/*immunology ; Humans ; Microbiota/*genetics/immunology ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA/methods ; Transplantation, Homologous/adverse effects ; }, abstract = {The human gastrointestinal tract, skin and mucosal surfaces are inhabited by a complex system of bacteria, viruses, fungi, archaea, protists, and eukaryotic parasites with predominance of bacteria and bacterial viruses (bacteriophages). Collectively these microbes form the microbiota of the microecosystem of humans. Recent advancement in technologies for nucleic acid isolation from various environmental samples, feces and body secretions and advancements in shotgun throughput massive parallel DNA and RNA sequencing along with 16S ribosomal gene sequencing have unraveled the identity of otherwise unknown microbial entities constituting the human microecosystem. The improved transcriptome analysis, technological developments in biochemical analytical methods and availability of complex bioinformatics tools have allowed us to begin to understand the metabolome of the microbiome and the biochemical pathways and potential signal transduction pathways in human cells in response to microbial infections and their products. Also, developments in human whole genome sequencing, targeted gene sequencing of histocompatibility genes and other immune response associated genes by Next Generation Sequencing (NGS) have allowed us to have a better conceptualization of immune responses, and alloimmune responses. These modern technologies have enabled us to dive into the intricate relationship between commensal symbiotic and pathogenic microbiome and immune system. For the most part, the commensal symbiotic microbiota helps to maintain normal immune homeostasis besides providing healthy nutrients, facilitating digestion, and protecting the skin, mucosal and intestinal barriers. However, changes in diets, administration of therapeutic agents like antibiotics, chemotherapeutic agents, immunosuppressants etc. along with certain host factors including human histocompatibility antigens may alter the microbial ecosystem balance by causing changes in microbial constituents, hierarchy of microbial species and even dysbiosis. Such alterations may cause immune dysregulation, breach of barrier protection and lead to immunopathogenesis rather than immune homeostasis. The effects of human microbiome on immunity, health and disease are currently under intense research with cutting edge technologies in molecular biology, biochemistry, and bioinformatics along with tremendous ability to characterize immune response at single cell level. This review will discuss the contemporary status on human microbiome immune system interactions and their potential effects on health, immune homeostasis and allograft transplantation.}, }
@article {pmid34363822, year = {2021}, author = {Zheng, W and Duan, M and Jia, J and Song, S and Ai, C}, title = {Low-molecular alginate improved diet-induced obesity and metabolic syndrome through modulating the gut microbiota in BALB/c mice.}, journal = {International journal of biological macromolecules}, volume = {187}, number = {}, pages = {811-820}, doi = {10.1016/j.ijbiomac.2021.08.003}, pmid = {34363822}, issn = {1879-0003}, mesh = {Adiposity ; *Alginates ; Animal Feed ; Animals ; Bacteria/*metabolism ; Biomarkers/blood ; Diet, High-Fat ; Disease Models, Animal ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Inflammation Mediators/metabolism ; Lipids/blood ; Male ; Metabolic Syndrome/blood/*diet therapy/microbiology ; Mice, Inbred BALB C ; Molecular Weight ; Obesity/blood/*diet therapy/microbiology ; *Prebiotics ; Weight Gain ; Mice ; }, abstract = {Alginate is the most abundant polysaccharide in brown seaweed, which is widely used as a food additive, but its high viscosity and gel property limit its applications in foods as a functional ingredient. In this study, low-molecular alginate from Laminaria japonica (L-LJA) was prepared, and its effect on obesity and metabolic syndrome was analyzed in high-fat diet (HFD)-fed mice. L-LJA reduced weight gain, fat accumulation in the liver and epididymal adipose tissue, lipid abnormality and inflammation in HFD-fed mice accompanied with the improvement of gut microbiota. L-LJA modulated the structure of gut microbiota, increased some Bacteroidales members, and reduced some Clostridiales members in mice, which were positively correlated with the improvement of physiological status. Fecal transplant from L-LJA-fed mice reduced fat accumulation in body tissues and lipid abnormality in the serum and liver and increased short chain fatty acids production in HFD-fed mice, confirming that L-LJA-induced gut microbiota alteration played an important role in its bioactivity. L-LJA has better solubility and can be utilized in food systems in high dose, implying that it can be developed as a prebiotic agent to increase both economic value and nutritive value of alginate.}, }
@article {pmid34362925, year = {2021}, author = {Zhang, AN and Gaston, JM and Dai, CL and Zhao, S and Poyet, M and Groussin, M and Yin, X and Li, LG and van Loosdrecht, MCM and Topp, E and Gillings, MR and Hanage, WP and Tiedje, JM and Moniz, K and Alm, EJ and Zhang, T}, title = {An omics-based framework for assessing the health risk of antimicrobial resistance genes.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4765}, pmid = {34362925}, issn = {2041-1723}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/drug effects/genetics ; Databases, Factual ; Drug Resistance, Bacterial/*drug effects/*genetics ; Gastrointestinal Microbiome/drug effects ; Genes, Bacterial/drug effects ; Genome ; Humans ; Metagenome ; Plasmids ; }, abstract = {Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an 'omics-based' framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as 'current threats' (Rank I; 3%) - already present among pathogens - and 'future threats' (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 'current threat' ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II ('future threats'). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions.}, }
@article {pmid34359902, year = {2021}, author = {Palma Albornoz, SP and Fraga-Silva, TFC and Gembre, AF and de Oliveira, RS and de Souza, FM and Rodrigues, TS and Kettelhut, IDC and Manca, CS and Jordao, AA and Ramalho, LNZ and Ribolla, PEM and Carlos, D and Bonato, VLD}, title = {Obesity-Induced Dysbiosis Exacerbates IFN-γ Production and Pulmonary Inflammation in the Mycobacterium tuberculosis Infection.}, journal = {Cells}, volume = {10}, number = {7}, pages = {}, pmid = {34359902}, issn = {2073-4409}, support = {2017/21629-5//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; }, mesh = {Adaptive Immunity ; Animals ; Bacterial Load ; Disease Susceptibility ; Dysbiosis/*etiology/immunology/*microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Interferon-gamma/*biosynthesis ; Leukocytes/metabolism ; Lung/immunology/microbiology/pathology ; Mice, Inbred C57BL ; Microbiota ; Obesity/*complications/immunology/*microbiology ; Pneumonia/immunology/*microbiology ; Tuberculosis/*complications/immunology ; Mice ; }, abstract = {The microbiota of the gut-lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4[+]IFN-γ[+]IL-17[-] cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut-lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology.}, }
@article {pmid34359501, year = {2021}, author = {Lee, BH and Hsu, WH and Chien, HY and Hou, CY and Hsu, YT and Chen, YZ and Wu, SC}, title = {Applications of Lactobacillus acidophilus-Fermented Mango Protected Clostridioides difficile Infection and Developed as an Innovative Probiotic Jam.}, journal = {Foods (Basel, Switzerland)}, volume = {10}, number = {7}, pages = {}, pmid = {34359501}, issn = {2304-8158}, abstract = {Clostridioides difficile infection (CDI) is a large intestine disease caused by toxins produced by the spore-forming bacterium C. difficile, which belongs to Gram-positive bacillus. Using antibiotics treatment disturbances in the gut microbiota and toxins produced by C. difficile disrupt the intestinal barrier. Some evidence indicates fecal microbiota transplantation and probiotics may decrease the risk of CDI recurrence. This study aimed to evaluate the efficacy of fermented mango by using the lactic acid bacteria Lactobacillus acidophilus and develop innovative products in the form of fermented mango jam. L. acidophilus-fermented mango products inhibited the growth of C. difficile while promoting the growth of next-generation probiotic Faecalibacterium prausnitzii. Both supernatant and precipitate of mango-fermented products prevented cell death in gut enterocyte-like Caco-2 cells against C. difficile infection. Mango-fermented products also protected gut barrier function by elevating the expression of tight junction proteins. Moreover, L. acidophilus-fermented mango jam with high hydrostatic pressure treatment had favorable textural characteristics and sensory quality.}, }
@article {pmid34358240, year = {2021}, author = {McDaniel Mims, B and Enriquez, J and Pires Dos Santos, A and Jones-Hall, Y and Dowd, S and Furr, KL and Grisham, MB}, title = {Antibiotic administration exacerbates acute graft vs. host disease-induced bone marrow and spleen damage in lymphopenic mice.}, journal = {PloS one}, volume = {16}, number = {8}, pages = {e0254845}, pmid = {34358240}, issn = {1932-6203}, support = {F31 AI145077/AI/NIAID NIH HHS/United States ; }, mesh = {Acute Disease ; Adoptive Transfer ; Animals ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Bacteria/classification/drug effects/growth &amp; development ; Blood Cell Count ; Bone Marrow/drug effects/*pathology ; CD4-Positive T-Lymphocytes/immunology/microbiology ; Cytokines/blood ; *Disease Progression ; Feces/microbiology ; Graft vs Host Disease/blood/complications/*drug therapy/pathology ; Inflammation/blood/complications/pathology ; Lymphopenia/blood/complications/*drug therapy ; Male ; Mice ; Phylogeny ; Spleen/drug effects/*pathology ; Transplantation, Homologous ; }, abstract = {BACKGROUND: Hematopoietic stem cell transplantation is a potential cure for certain life-threatening malignant and nonmalignant diseases. However, experimental and clinical studies have demonstrated that pre-transplant myeloablative conditioning damages the gut leading to translocation of intestinal bacteria and the development of acute graft vs. host disease (aGVHD). The overall objective of this study was to determine whether administration of broad spectrum antibiotics (Abx) affects the onset and/or severity of aGVHD in lymphopenic mice that were not subjected to toxic, pre-transplant conditioning.<br><br>RESULTS: We found that treatment of NK cell-depleted recombination activating gene-1-deficient (-NK/RAG) recipients with an Abx cocktail containing vancomycin and neomycin for 7 days prior to and 4 weeks following adoptive transfer of allogeneic CD4+ T cells, exacerbated the development of aGVHD-induced BM failure and spleen damage when compared to untreated-NK/RAG recipients engrafted with syngeneic or allogeneic T cells. Abx-treated mice exhibited severe anemia and monocytopenia as well as marked reductions in BM- and spleen-residing immune cells. Blinded histopathological analysis confirmed that Abx-treated mice engrafted with allogeneic T cells suffered significantly more damage to the BM and spleen than did untreated mice engrafted with allogeneic T cells. Abx-induced exacerbation of BM and spleen damage correlated with a dramatic reduction in fecal bacterial diversity, marked loss of anaerobic bacteria and remarkable expansion of potentially pathogenic bacteria.<br><br>CONCLUSIONS: We conclude that continuous Abx treatment may aggravate aGVHD-induced tissue damage by reducing short chain fatty acid-producing anaerobes (e.g. Clostridium, Blautia) and/or by promoting the expansion of pathobionts (e.g. Akkermansia) and opportunistic pathogens (Cronobacter).}, }
@article {pmid34356911, year = {2021}, author = {Gozalbo-Rovira, R and Santiso-Bellón, C and Buesa, J and Rubio-Del-Campo, A and Vila-Vicent, S and Muñoz, C and Yebra, MJ and Monedero, V and Rodríguez-Díaz, J}, title = {Microbiota Depletion Promotes Human Rotavirus Replication in an Adult Mouse Model.}, journal = {Biomedicines}, volume = {9}, number = {7}, pages = {}, pmid = {34356911}, issn = {2227-9059}, support = {AGL2017-84165-C2-1-R//Ministerio de Ciencia y Tecnolog&#xed;a/ ; AGL2017-84165-C2-2-R//Ministerio de Ciencia y Tecnolog&#xed;a/ ; }, abstract = {Intestinal microbiota-virus-host interaction has emerged as a key factor in mediating enteric virus pathogenicity. With the aim of analyzing whether human gut bacteria improve the inefficient replication of human rotavirus in mice, we performed fecal microbiota transplant (FMT) with healthy infants as donors in antibiotic-treated mice. We showed that a simple antibiotic treatment, irrespective of FMT, resulted in viral shedding for 6 days after challenge with the human rotavirus G1P[8] genotype Wa strain (RVwa). Rotavirus titers in feces were also significantly higher in antibiotic-treated animals with or without FMT but they were decreased in animals subject to self-FMT, where a partial re-establishment of specific bacterial taxons was evidenced. Microbial composition analysis revealed profound changes in the intestinal microbiota of antibiotic-treated animals, whereas some bacterial groups, including members of Lactobacillus, Bilophila, Mucispirillum, and Oscillospira, recovered after self-FMT. In antibiotic-treated and FMT animals where the virus replicated more efficiently, differences were observed in gene expression of immune mediators, such as IL1β and CXCL15, as well as in the fucosyltransferase FUT2, responsible for H-type antigen synthesis in the small intestine. Collectively, our results suggest that antibiotic-induced microbiota depletion eradicates the microbial taxa that restrict human rotavirus infectivity in mice.}, }
@article {pmid34355542, year = {2021}, author = {Lee, MH}, title = {Harness the functions of gut microbiome in tumorigenesis for cancer treatment.}, journal = {Cancer communications (London, England)}, volume = {41}, number = {10}, pages = {937-967}, pmid = {34355542}, issn = {2523-3548}, support = {2020YFA0803300//National key research and development program/ ; 2018YFC0910300//National key research and development program/ ; 81630072//National Natural Science Foundation of China/ ; KQTD20170810160226082//Shenzhen Municipal Government of China/ ; 2018YFC0910300//China Association for Science and Technology/ ; 2020YFA0803300//China Association for Science and Technology/ ; }, mesh = {Carcinogenesis/genetics ; *Gastrointestinal Microbiome/genetics ; Humans ; *Neoplasms/genetics/therapy ; }, abstract = {It has been shown that gut microbiota dysbiosis leads to physiological changes and links to a number of diseases, including cancers. Thus, many cancer categories and treatment regimens should be investigated in the context of the microbiome. Owing to the availability of metagenome sequencing and multiomics studies, analyses of species characterization, host genetic changes, and metabolic profile of gut microbiota have become feasible, which has facilitated an exponential knowledge gain about microbiota composition, taxonomic alterations, and host interactions during tumorigenesis. However, the complexity of the gut microbiota, with a plethora of uncharacterized host-microbe, microbe-microbe, and environmental interactions, still contributes to the challenge of advancing our knowledge of the microbiota-cancer interactions. These interactions manifest in signaling relay, metabolism, immunity, tumor development, genetic instability, sensitivity to cancer chemotherapy and immunotherapy. This review summarizes current studies/molecular mechanisms regarding the association between the gut microbiota and the development of cancers, which provides insights into the therapeutic strategies that could be harnessed for cancer diagnosis, treatment, or prevention.}, }
@article {pmid34354704, year = {2021}, author = {Wang, D and Shao, S and Zhang, Y and Zhao, D and Wang, M}, title = {Insight Into Polysaccharides From Panax ginseng C. A. Meyer in Improving Intestinal Inflammation: Modulating Intestinal Microbiota and Autophagy.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {683911}, pmid = {34354704}, issn = {1664-3224}, mesh = {Animals ; Autophagy/*drug effects ; Colitis/chemically induced/microbiology/pathology/*therapy ; Cytokines/metabolism ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects ; HT29 Cells ; Humans ; Intestinal Mucosa/metabolism ; Male ; Oxidative Stress/drug effects ; Panax/*chemistry ; Plant Extracts/pharmacology ; Polysaccharides/*pharmacology ; Rats ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {Polysaccharides from Panax ginseng C. A. Meyer (P. ginseng) are the main active component of P. ginseng and exhibit significant intestinal anti-inflammatory activity. However, the therapeutic mechanism of the ginseng polysaccharide is unclear, and this hinders the application for medicine or functional food. In this study, a polysaccharide was isolated from P. ginseng (GP). The primary structure and morphology of the GP were studied by HPLC, FT-IR spectroscopy, and scanning electron microscopy (SEM). Further, its intestinal anti-inflammatory activity and its mechanism of function were evaluated in experimental systems using DSS-induced rats, fecal microbiota transplantation (FMT), and LPS-stimulated HT-29 cells. Results showed that GP modulated the structure of gut microbiota and restored mTOR-dependent autophagic dysfunction. Consequently, active autophagy suppressed inflammation through the inhibition of NF-κB, oxidative stress, and the release of cytokines. Therefore, our research provides a rationale for future investigations into the relationship between microbiota and autophagy and revealed the therapeutic potential of GP for inflammatory bowel disease.}, }
@article {pmid34349661, year = {2021}, author = {Choi, YJ and Kim, JE and Lee, SJ and Gong, JE and Son, HJ and Hong, JT and Hwang, DY}, title = {Dysbiosis of Fecal Microbiota From Complement 3 Knockout Mice With Constipation Phenotypes Contributes to Development of Defecation Delay.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {650789}, pmid = {34349661}, issn = {1664-042X}, abstract = {Significant phenotypes for constipation were detected in complement 3 (C3) knockout (KO) mice, although no research has been conducted on an association with alteration of gut microbiota. To investigate the effects of dysbiosis on fecal microbiota from C3 KO mice with constipation, the composition of fecal microbiota was characterized in mid-colons of 16-week-old C3 KO mice, and their function for defecation delay development was examined after fecal microbiota transplantation (FMT) of C3 KO mice. Some significant alterations in constipation phenotypes, including stool parameters and histopathological structure, were detected in 16-week-old C3 KO mice compared to those of wild-type (WT) mice. Fecal microbiota of C3 KO mice exhibited decreases in Anaerocolumna, Caecibacterium, Christensenella, Kineothrix, and Oscillibacter populations and increases in Prevotellamassilia, Reuthenibacterium, Prevotella, Eubacterium, Culturomica, Bacteroides, and Muribaculum populations. In FMT study, key stool parameters, including weight and water content, were remarkably declined in a transplanted KO (KFMT) group of antibiotics-induced depletion of microbiota (AiDM)-WT and AiDM-KO mice, and a similar change was observed in fecal morphology. However, intestine length decreased in only the KFMT group of AiDM-WT mice compared with that of AiDM-KO mice. The mucosal layer and muscle thickness were commonly decreased in the KFMT group of AiDM-WT and AiDM-KO mice, and significant alterations in the crypt structure of Lieberkuhn and molecular regulators, including AQP8, C-kit, and 5-HT, were observed in the same group. Taken together, results of the present study indicate that dysbiosis of fecal microbiota from C3 KO mice with constipation phenotypes has a key role in the induction and regulation of defecation delay.}, }
@article {pmid34347266, year = {2021}, author = {Zhong, Z and Chen, W and Gao, H and Che, N and Xu, M and Yang, L and Zhang, Y and Ye, M}, title = {Fecal Microbiota Transplantation Exerts a Protective Role in MPTP-Induced Parkinson's Disease via the TLR4/PI3K/AKT/NF-κB Pathway Stimulated by α-Synuclein.}, journal = {Neurochemical research}, volume = {46}, number = {11}, pages = {3050-3058}, pmid = {34347266}, issn = {1573-6903}, mesh = {Animals ; Fecal Microbiota Transplantation/*methods ; Male ; Mice ; Mice, Inbred C57BL ; NF-kappa B/*antagonists &amp; inhibitors/metabolism ; Neuroprotection/physiology ; Parkinsonian Disorders/chemically induced/metabolism/*prevention &amp; control ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/*antagonists &amp; inhibitors/metabolism ; Toll-Like Receptor 4/*antagonists &amp; inhibitors/metabolism ; alpha-Synuclein/*antagonists &amp; inhibitors/metabolism ; }, abstract = {Gut microbiota is closely related to the Parkinson's disease (PD) pathogenesis. Additionally, aggregation of α-synuclein (α-syn) is central to PD pathogenesis. Here we identified the further mechanisms of gut microbiota in PD. A mouse model with PD was established via injection of MPTP. Normal or MPTP-induced PD like animals were treated with FMT from healthy normal mice. Pole test and traction test were performed to examine the effects of FMT on motor function of PD mice. Fecal SCFAs were assessed by gas chromatography-mass spectrometry. The α-syn level in the substantia nigra pars compacta (SN) of mice was measured using western blot. Dopaminergic neurons and microglial activation in the SN were analyzed by immunohistochemistry (IHC) and immunofluorescence (IF) staining. FMT alleviated physical impairment, decreased fecal SCFAs in a mouse model of PD. Additionally, FMT decreased the expression of α-syn, as well as inhibited the activation of microglia in the SN, and blocked the TLR4/PI3K/AKT/NF-κB signaling in the SN and striatum. FMT could protect mice against PD via suppressing α-syn expression and inactivating the TLR4/PI3K/AKT/NF-κB signaling.}, }
@article {pmid34346283, year = {2021}, author = {Bajaj, JS and Shamsaddini, A and Fagan, A and McGeorge, S and Gavis, E and Sikaroodi, M and Brenner, LA and Wade, JB and Gillevet, PM}, title = {Distinct gut microbial compositional and functional changes associated with impaired inhibitory control in patients with cirrhosis.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1953247}, pmid = {34346283}, issn = {1949-0984}, support = {I01 CX001076/CX/CSRD VA/United States ; R01 HS025412/HS/AHRQ HHS/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; R21 TR003095/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; *Gastrointestinal Microbiome ; Hepatic Encephalopathy/*etiology/*physiopathology ; Humans ; Liver Cirrhosis/*complications/*microbiology/*physiopathology ; Male ; Middle Aged ; Severity of Illness Index ; }, abstract = {Most cirrhosis etiologies, such as alcohol, hepatitis C, and obesity, involve behavior that require the loss of inhibitory control. Once cirrhosis develops, patients can also develop cognitive impairment due to minimal hepatic encephalopathy (MHE). Both processes could have distinct imprints on the gut-liver-brain axis. Determine the impact of inhibitory control versus traditional cirrhosis-related cognitive performance on gut microbial composition and function. Outpatients with cirrhosis underwent two tests for MHE: inhibitory control test (MHEICT, computerized associated with response inhibition) and psychometric hepatic encephalopathy score (MHEPHES, paper-pencil HE-specific associated with subcortical impairment) along with stool collection for metagenomics. MHEICT/not, MHEPHES/not, and discordant (positive on one test but negative on the other) were analyzed for demographics, bacterial species, and gut-brain modules (GBM) using multi-variable analyses. Ninety-seven patients [47 (49%) MHEPHES, 76 (78%) MHEICT, 41 discordant] were enrolled. MHEPHES/not: Cirrhosis severity was worse in MHEPHES without differences in alpha/beta diversity on bacterial species or GBMs. Pathobionts (Enterobacteriaceae) and γ-amino-butryic acid (GABA) synthesis GBM were higher in MHEPHES. MHEICT/not: We found similar cirrhosis severity and metagenomic alpha/beta diversity in MHEICT versus not. However, alpha/beta diversity of GBMs were different in MHEICT versus No-MHE patients. Alistipes ihumii, Prevotella copri, and Eubacterium spp. were higher, while Enterococcus spp. were uniquely lower in MHEICT versus no-MHE and discordant comparisons. GBMs belonging to tryptophan, menaquinone, GABA, glutamate, and short-chain fatty acid synthesis were also unique to MHEICT. Gut microbial signature of impaired inhibitory control, which is associated with addictive disorders that can lead to cirrhosis, is distinct from cirrhosis-related cognitive impairment.}, }
@article {pmid34343321, year = {2021}, author = {Conrad, MA and Kelsen, JR}, title = {Clostridioides difficile Infection in Pediatric Inflammatory Bowel Disease: A Clinician's Dilemma.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {10}, number = {Supplement_3}, pages = {S41-S45}, pmid = {34343321}, issn = {2048-7207}, support = {K23 DK119585/DK/NIDDK NIH HHS/United States ; }, mesh = {Child ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/complications/diagnosis ; Humans ; *Inflammatory Bowel Diseases/complications/diagnosis ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection (CDI) in children with inflammatory bowel disease (IBD) can present and manifest differently from the general population with CDI, and it can worsen the underlying disease course. Furthermore, current clinical assays used to test for CDI do not accurately distinguish between true CDI or colonization. This uncertainty leads to difficulty in identifying the etiology and therapy for symptomatic patients with IBD. Improved diagnostic tests, biomarkers, and safe and effective treatment options are greatly needed for this vulnerable population.}, }
@article {pmid34341834, year = {2021}, author = {Zhang, M and Hong, Y and Wu, W and Li, N and Liu, B and Sun, J and Cao, X and Ye, T and Zhou, L and Liu, C and Yang, C and Zhang, X}, title = {Pivotal role of the gut microbiota in congenital insensitivity to pain with anhidrosis.}, journal = {Psychopharmacology}, volume = {238}, number = {11}, pages = {3131-3142}, pmid = {34341834}, issn = {1432-2072}, support = {81974171//Natural Science Foundation Project of China/ ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; *Hereditary Sensory and Autonomic Neuropathies ; Humans ; Mice ; }, abstract = {BACKGROUND: Increasing evidence has shown that the occurrence and development of various human diseases are closely related to the gut microbiota. We compared the gut microbial communities of human subjects with congenital insensitivity to pain with anhidrosis (CIPA) and healthy controls (HCs) to assess whether fecal microbiota transplantation (FMT) into germ-free mice and mice in acute pain influenced the behaviors of the host.<br><br>METHODS: We utilized 16&#xa0;s rRNA analysis to compare the gut microbial communities of CIPA subjects and HCs and assessed whether FMT into germ-free mice and mice in acute pain influenced the behaviors of the host.<br><br>RESULTS: In a 16&#xa0;s RNA analysis, the CIPA group had significant decreases in the relative abundance of 11 bacteria, whereas 7 bacteria were significantly increased. In further animal experiments, the transplantation of fecal samples from CIPA patients to healthy mice significantly increased their scores on both the mechanical withdrawal test and the tail flick test; in an acute plantar incision model, scores were also significantly increased on the mechanical withdrawal test at 4 and 5&#xa0;days after the operation. Moreover, pseudo-germ-free mice receiving fecal bacteria from patients with CIPA took significantly longer to escape and had a significantly longer path length on training days 1, 2, and 5 and also had fewer platform crossings and spent less time in the target quadrant in the probe trial.<br><br>CONCLUSIONS: Our results suggest that the gut microbiota in CIPA subjects plays a key role in behaviors. Therapeutic strategies for improving the gut microbiota might alleviate CIPA symptoms.}, }
@article {pmid34336729, year = {2021}, author = {MacLellan, AD and Finlay, BB and Appel-Cresswell, S}, title = {Age-Matching in Pediatric Fecal Matter Transplants.}, journal = {Frontiers in pediatrics}, volume = {9}, number = {}, pages = {603423}, pmid = {34336729}, issn = {2296-2360}, }
@article {pmid34335628, year = {2021}, author = {Brosseau, C and Selle, A and Duval, A and Misme-Aucouturier, B and Chesneau, M and Brouard, S and Cherbuy, C and Cariou, V and Bouchaud, G and Mincham, KT and Strickland, DH and Barbarot, S and Bodinier, M}, title = {Prebiotic Supplementation During Pregnancy Modifies the Gut Microbiota and Increases Metabolites in Amniotic Fluid, Driving a Tolerogenic Environment In Utero.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {712614}, pmid = {34335628}, issn = {1664-3224}, mesh = {Acetates/metabolism ; Amniotic Fluid/*metabolism ; Animals ; B-Lymphocyte Subsets/immunology ; Butyrates/metabolism ; Dendritic Cells/immunology ; *Dietary Supplements ; Feces/chemistry/microbiology ; Female ; Fetus/immunology ; *Gastrointestinal Microbiome ; Humans ; *Immune Tolerance ; Inulin/administration &amp; dosage/pharmacology ; Maternal-Fetal Exchange ; Mice ; Mice, Inbred BALB C ; Oligosaccharides/administration &amp; dosage/pharmacology ; Placenta/cytology/immunology ; *Prebiotics ; Pregnancy ; Pregnancy Outcome ; *Pregnancy, Animal/immunology/metabolism ; Prenatal Exposure Delayed Effects ; Propionates/metabolism ; Ribotyping ; T-Lymphocyte Subsets/immunology ; Uterus/cytology/immunology ; }, abstract = {The gut microbiota is influenced by environmental factors such as food. Maternal diet during pregnancy modifies the gut microbiota composition and function, leading to the production of specific compounds that are transferred to the fetus and enhance the ontogeny and maturation of the immune system. Prebiotics are fermented by gut bacteria, leading to the release of short-chain fatty acids that can specifically interact with the immune system, inducing a switch toward tolerogenic populations and therefore conferring health benefits. In this study, pregnant BALB/cJRj mice were fed either a control diet or a diet enriched in prebiotics (Galacto-oligosaccharides/Inulin). We hypothesized that galacto-oligosaccharides/inulin supplementation during gestation could modify the maternal microbiota, favoring healthy immune imprinting in the fetus. Galacto-oligosaccharides/inulin supplementation during gestation increases the abundance of Bacteroidetes and decreases that of Firmicutes in the gut microbiota, leading to increased production of fecal acetate, which was found for the first time in amniotic fluid. Prebiotic supplementation increased the abundance of regulatory B and T cells in gestational tissues and in the fetus. Interestingly, these regulatory cells remained later in life. In conclusion, prebiotic supplementation during pregnancy leads to the transmission of specific microbial and immune factors from mother to child, allowing the establishment of tolerogenic immune imprinting in the fetus that may be beneficial for infant health outcomes.}, }
@article {pmid34335508, year = {2021}, author = {Zhu, F and Ke, Y and Luo, Y and Wu, J and Wu, P and Ma, F and Liu, Y}, title = {Effects of Different Treatment of Fecal Microbiota Transplantation Techniques on Treatment of Ulcerative Colitis in Rats.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {683234}, pmid = {34335508}, issn = {1664-302X}, abstract = {Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease with abdominal pain, mucus, pus and blood in the stool as the main clinical manifestations. The pathogenesis of UC is still not completely clear, and multiple factors, such as genetic susceptibility, immune response, intestinal microecological changes and environmental factors, together lead to the onset of UC. In recent years, the role of intestinal microbiota disturbances on the pathogenesis of UC has received widespread attention. Therefore, fecal microbiota transplantation (FMT), which changes the intestinal microecological environment of UC patients by transplantation of normal fecal bacteria, has attracted increasing attention from researchers. However, there are no guidelines to recommend fresh FMT or frozen FMT in the treatment of UC, and there are few studies on this. Therefore, the purpose of this study was to explore the effects of fresh and frozen FMT methods on the treatment of experimental UC models in rats. Results: Compared with the model control group, all FMT groups achieved better efficacy, mainly manifested as weight gain by the rats, improvements in fecal characteristics and blood stools, reduced inflammatory factors and normal bacterial microbiota. The efficacy of the frozen FMT group was better than that of the fresh FMT group in terms of behavior and colon length. Conclusion: FMT method supplements the gut microbiota with beneficial bacteria, such as short-chain fatty acid-producing bacteria. These bacteria can regulate intestinal function, protect the mucosal barrier and reduce harmful bacteria, thus mitigating the damage to the intestinal barrier and the associated inflammatory response, resulting in UC remission. FMT is a feasible method for treating UC, with frozen FMT having a superior therapeutic effect than that of fresh FMT.}, }
@article {pmid34333726, year = {2022}, author = {Concas, G and Barone, M and Francavilla, R and Cristofori, F and Dargenio, VN and Giorgio, R and Dargenio, C and Fanos, V and Marcialis, MA}, title = {Twelve Months with COVID-19: What Gastroenterologists Need to Know.}, journal = {Digestive diseases and sciences}, volume = {67}, number = {7}, pages = {2771-2791}, pmid = {34333726}, issn = {1573-2568}, mesh = {*COVID-19 ; *Gastroenterologists ; *Gastrointestinal Diseases/diagnosis/therapy ; Humans ; Pandemics ; SARS-CoV-2 ; }, abstract = {Corona virus disease-19 (COVID-19) is the latest global pandemic. COVID-19 is mainly transmitted through respiratory droplets and, apart from respiratory symptoms, patients often present with gastrointestinal symptoms and liver involvement. Given the high percentage of COVID-19 patients that present with gastrointestinal symptoms (GIS), in this review, we report a practical up-to-date reference for the physician in their clinical practice with patients affected by chronic gastrointestinal (GI) diseases (inflammatory bowel disease, coeliac disease, chronic liver disease) at the time of COVID-19. First, we summarised data on the origin and pathogenetic mechanism of SARS-CoV-2. Then, we performed a literature search up to December 2020 examining clinical manifestations of GI involvement. Next, we illustrated and summarised the most recent guidelines on how to adhere to GI procedures (endoscopy, liver biopsy, faecal transplantation), maintaining social distance and how to deal with immunosuppressive treatment. Finally, we focussed on some special conditions such as faecal-oral transmission and gut microbiota. The rapid accumulation of information relating to this condition makes it particularly essential to revise the literature to take account of the most recent publications for medical consultation and patient care.}, }
@article {pmid34332209, year = {2021}, author = {Corrie, L and Gulati, M and Vishwas, S and Kapoor, B and Singh, SK and Awasthi, A and Khursheed, R}, title = {Combination therapy of curcumin and fecal microbiota transplant: Potential treatment of polycystic ovarian syndrome.}, journal = {Medical hypotheses}, volume = {154}, number = {}, pages = {110644}, doi = {10.1016/j.mehy.2021.110644}, pmid = {34332209}, issn = {1532-2777}, mesh = {*Curcumin/therapeutic use ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Female ; Humans ; *Microbiota ; *Polycystic Ovary Syndrome/therapy ; }, abstract = {Polycystic ovarian syndrome (PCOS) is a combination of various symptoms like anovulation, hirsutism, chronic amenorrhea, infertility, obesity and polycystic ovaries. It affects over 7 million women worldwide. The current strategy to treat this disorder is based on the use of drugs that provide symptomatic relief. Most of these, however, exhibit numerous side effects and are not able to ameliorate all the signs and symptoms of PCOS. As dysbiosis is considered as one of the prime underlying causes of PCOS, restoration of eubiosis was considered as a plausible way to treat it. Bacteriotherpeutics like probiotics, synbiotics and even fecal microbiota transplant (FMT) have shown considerable effectiveness in PCOS. Of these baceteriotherapeutic options, FMT is considered to be the most holistic as it encompasses the bacteriome, virome, fungome, archaeome and even parasitome while both probiotics as well as synbiotics mainly comprise bacteria. Repeated FMT, however, is not a pragmatic option because of its inconvenience, lack of standardization, involved risk and scepticism amongst patients and physicians. If the eubiosis ushered by FMT is sustained for a long time, the repeated administrations of FMT can be avoided and maintenance therapy with any agent that can maintain the eubiotic condition can be adopted. Role of curcumin on gut microbiota is widely known. It is largely attributed to the ability of certain microbes to consume polyphenols as substrates and its positive effect on bacterial consumption of nutrients such as sugars. Based on various mechanisms and studies, a new hypothesis is being proposed wherein FMT and curcumin combination is predicted to be an effective and sustained treatment of PCOS with much lower rates of remission.}, }
@article {pmid34330600, year = {2021}, author = {Ji, Y and Tao, T and Zhang, J and Su, A and Zhao, L and Chen, H and Hu, Q}, title = {Comparison of effects on colitis-associated tumorigenesis and gut microbiota in mice between Ophiocordyceps sinensis and Cordyceps militaris.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {90}, number = {}, pages = {153653}, doi = {10.1016/j.phymed.2021.153653}, pmid = {34330600}, issn = {1618-095X}, mesh = {Animals ; Bacteroidetes ; Bifidobacterium ; Carcinogenesis ; *Colitis/chemically induced/drug therapy ; *Cordyceps/chemistry ; Dextran Sulfate ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Probiotics ; }, abstract = {BACKGROUND: Gut microbiota plays an indispensable role in the treatment of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). As traditional medicinal fungi, previous studies have shown that Ophiocordyceps sinensis could better maintain intestinal health via promoting the growth of probiotics in vitro compared with Cordyceps militaris. However, the detailed pharmacological activities and clinical efficacy of O. sinensis and C. militaris are still elusive.<br><br>PURPOSE: We aimed to evaluate the different actions of O. sinensis and C. militaris on colitis-associated tumorigenesis in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice and explore the potential gut microbiota-dependent mechanisms.<br><br>METHODS: C57BL/6 mice (Male, 4 weeks old) were used to construct the AOM/DSS-induced CAC mice model. The mice were administered with 0.6 mg/g/d O. sinensis or C. militaris for 12 weeks. It's worth noting that fecal microbiota transplantation (FMT) and antibiotic treatment were used to investigated the complex interactions between the medicinal fungi, gut microbiota and colonic tumorigenesis.<br><br>RESULTS: O. sinensis treatment significantly increased the body weight and survival rate, reduced the number of colon tumors, improved the damage of colon epithelial tissue, restored the crypt structure and alleviate the colonic inflammation in AOM/DSS-treated mice. RT-qPCR results indicated that O. sinensis partly regulated the Wnt/&#x3b2;-catenin signaling via alleviating the overexpression of &#x3b2;-catenin, TCF4 and c-Myc genes in adjacent noncancerous tissues. Compared with C. militaris, O. sinensis showed better anti-tumor activity. Gut microbiota analysis revealed that O. sinensis reversed the decline of gut microbiota diversity and the structural disorder induced by AOM/DSS. Spearman's correlation analysis showed that O. sinensis promoted the growth of Parabacteroides goldsteinii and Bifidobacterium pseudolongum PV8-2, which were positively correlated with the anti-tumor activity and the production of SCFAs. FMT combined with antibiotic treatment showed that horizontal fecal transfer derived from O. sinensis-treated mice improved the intestinal inflammation and alleviated the colitis-associated tumorigenesis, which was consistent with the direct ingestion of O. sinensis.<br><br>CONCLUSION: O. sinensis could better attenuate colitis-associated tumorigenesis compared with C. militaris. These effects might be at least partially due to the increased abundance of probiotics, especially P. goldsteinii and B. pseudolongum PV8-2.}, }
@article {pmid34329563, year = {2021}, author = {Sehgal, K and Khanna, S}, title = {Gut microbiota: a target for intervention in obesity.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {15}, number = {10}, pages = {1169-1179}, doi = {10.1080/17474124.2021.1963232}, pmid = {34329563}, issn = {1747-4132}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Combined Modality Therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Obesity/*microbiology/physiopathology/*therapy ; *Prebiotics ; Probiotics/*therapeutic use ; }, abstract = {INTRODUCTION: Obesity is a major public health concern with an increasing prevalence. Recent studies suggest an influence of gastrointestinal microbiota on obesity. Consequently, microbiota restoration therapies are being considered as potential management. We present data on microbiome markers and the future of microbiota therapeutics for obesity.<br><br>AREAS COVERED: We summarize the pathogenesis of obesity, relationship between gut microbiota and obesity, use of microbiota-based therapies. Data were gathered by a literature search of articles in PubMed from the date of inception till August 2020. Keywords used were 'gut microbiota,' 'gut microbiome,' 'microbiota,' 'microbiome,' 'obesity,' and 'obesity and fecal microbiota transplantation' as MeSH terms.<br><br>EXPERT OPINION: The direct relationship of gut microbiota in causing obesity needs exploration. Because of the scarcity of human studies, the utility of microbiota-based therapies as treatment remains uncertain and the use of microbiome restoration for obesity should be restricted to research settings. To evaluate the efficacy of microbiota restoration, studies using these therapies as an adjunct with diet and lifestyle should be conducted. Once relationships between bacterial strains and the human metabolic profile are determined, these strains could be cultured for transfer to obese patients. Such advancement could help in tailoring personalized therapies for obese persons.}, }
@article {pmid34328191, year = {2021}, author = {Nishikawa, H and Fukunishi, S and Asai, A and Yokohama, K and Ohama, H and Nishiguchi, S and Higuchi, K}, title = {Dysbiosis and liver diseases (Review).}, journal = {International journal of molecular medicine}, volume = {48}, number = {3}, pages = {}, doi = {10.3892/ijmm.2021.5016}, pmid = {34328191}, issn = {1791-244X}, mesh = {Animals ; Disease Progression ; Dysbiosis/*complications/pathology ; *Gastrointestinal Microbiome ; Humans ; Liver/pathology ; Liver Diseases/*etiology/pathology ; }, abstract = {Dysbiosis, a qualitative and quantitative aberrancy of gut microbiota, has attracted marked attention. At present, advances in molecular biological techniques have made it possible to analyze gut microbiota at the DNA and RNA levels without culturing, and methods such as 16S ribosomal RNA targeting analysis and metagenomic analysis using next‑generation sequencers have been developed. The relationship between gut microbiota and various diseases has been extensively examined. Gut microbiota are essential for the immune system, energy intake and fat storage, and humans use them to build complex immune regulatory mechanisms and to obtain energy from food. The liver is the first organ to be nourished by the portal blood flow of intestinal origin, and liver diseases can be strongly influenced by various factors of intestinal origin, such as intestinal bacteria, bacterial components, and intestinal bacterial metabolites. Rigorous research has revealed that the composition of the gut microbiota is altered and the diversity of bacteria is reduced in liver diseases. Significance of various factors transported to the liver by portal vein blood flow from the intestine has been extensively investigated. Gut microbiota in liver disease can be associated with disease progression regardless of disease etiology and even with carcinogenesis. The relationship between gut microbiota and liver diseases (hepatitis virus‑related diseases, autoimmune liver diseases, alcoholic liver disease, non‑alcoholic fatty liver disease, non‑alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma) and the treatments of dysbiosis (antibiotics, prebiotics, probiotics and fecal microbiota transplantation) in liver disease are outlined based on the current evidence.}, }
@article {pmid34328058, year = {2021}, author = {Gheorghe, CE and Ritz, NL and Martin, JA and Wardill, HR and Cryan, JF and Clarke, G}, title = {Investigating causality with fecal microbiota transplantation in rodents: applications, recommendations and pitfalls.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1941711}, pmid = {34328058}, issn = {1949-0984}, mesh = {Animal Experimentation/*standards ; Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation/*standards ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; *Guidelines as Topic ; Humans ; Rodentia/*microbiology ; }, abstract = {In recent years, studies investigating the role of the gut microbiota in health and diseases have increased enormously - making it essential to deepen and question the research methodology employed. Fecal microbiota transplantation (FMT) in rodent studies (either from human or animal donors) allows us to better understand the causal role of the intestinal microbiota across multiple fields. However, this technique lacks standardization and requires careful experimental design in order to obtain optimal results. By comparing several studies in which rodents are the final recipients of FMT, we summarize the common practices employed. In this review, we document the limitations of this method and highlight different parameters to be considered while designing FMT Studies. Standardizing this method is challenging, as it differs according to the research topic, but avoiding common pitfalls is feasible. Several methodological questions remain unanswered to this day and we offer a discussion on issues to be explored in future studies.}, }
@article {pmid34324703, year = {2021}, author = {Mengoni, F and Salari, V and Kosenkova, I and Tsenov, G and Donadelli, M and Malerba, G and Bertini, G and Del Gallo, F and Fabene, PF}, title = {Gut microbiota modulates seizure susceptibility.}, journal = {Epilepsia}, volume = {62}, number = {9}, pages = {e153-e157}, pmid = {34324703}, issn = {1528-1167}, mesh = {Animals ; Brain ; Brain-Gut Axis ; *Epilepsy ; *Gastrointestinal Microbiome ; Mice ; Seizures ; }, abstract = {A bulk of data suggest that the gut microbiota plays a role in a broad range of diseases, including those affecting the central nervous system. Recently, significant differences in the intestinal microbiota of patients with epilepsy, compared to healthy volunteers, have been reported in an observational study. However, an active role of the intestinal microbiota in the pathogenesis of epilepsy, through the so-called "gut-brain axis," has yet to be demonstrated. In this study, we evaluated the direct impact of microbiota transplanted from epileptic animals to healthy recipient animals, to clarify whether the microbiota from animals with epilepsy can affect the excitability of the recipients' brain by lowering seizure thresholds. Our results provide the first evidence that mice who received microbiota from epileptic animals are more prone to develop status epilepticus, compared to recipients of "healthy" microbiota, after a subclinical dose of pilocarpine, indicating a higher susceptibility to seizures. The lower thresholds for seizure activity found in this study support the hypothesis that the microbiota, through the gut-brain axis, is able to affect neuronal excitability in the brain.}, }
@article {pmid34321175, year = {2020}, author = {Yang, F and Chen, H and Gao, Y and An, N and Li, X and Pan, X and Yang, X and Tian, L and Sun, J and Xiong, X and Xing, Y}, title = {Gut microbiota-derived short-chain fatty acids and hypertension: Mechanism and treatment.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {130}, number = {}, pages = {110503}, doi = {10.1016/j.biopha.2020.110503}, pmid = {34321175}, issn = {1950-6007}, mesh = {Animals ; Disease Management ; Disease Susceptibility ; Dysbiosis ; Fatty Acids, Volatile/*metabolism ; *Gastrointestinal Microbiome ; Gene Expression Regulation ; Histones/metabolism ; Host-Pathogen Interactions ; Humans ; Hypertension/diagnosis/*etiology/*metabolism/therapy ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; }, abstract = {Hypertension (HTN) is an growing emerging health issue around across the world. In recent years, increasing attention has been paid to the role of dysbacteriosis in HTN and its underlying mechanism. Short-chain fatty acids (SCFAs), which are novel metabolites of intestinal flora, exert substantial regulatory effects on HTN, providing an exciting avenue for novel therapies for this disease. They function primarily by activating transmembrane G protein-coupled receptors and inhibiting histone acetylation. In this review, we discuss the mechanisms underlying the complex interaction between SCFAs and gut microbiota composition to lower blood pressure by regulating the brain-gut and kidney-gut axes, and the role of high-salt diet, immune system, oxidative stress, and inflammatory mechanism in the development of HTN. Furthermore, we also discuss the various treatment strategies for HTN, including diet, antibiotics, probiotics, fecal microflora transplantation, and traditional Chinese medicine. In conclusion, manipulation of SCFAs opens new avenues to improve treatment of HTN.}, }
@article {pmid34320242, year = {2021}, author = {Li, Y and Dong, J and Xiao, H and Wang, B and Chen, Z and Zhang, S and Jin, Y and Li, Y and Fan, S and Cui, M}, title = {Caloric restriction alleviates radiation injuries in a sex-dependent fashion.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {8}, pages = {e21787}, doi = {10.1096/fj.202100351RR}, pmid = {34320242}, issn = {1530-6860}, mesh = {Animals ; *Caloric Restriction ; Feces/microbiology ; Female ; Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Hematopoiesis/*radiation effects ; Inflammation/therapy ; Male ; Mice ; Mice, Inbred C57BL ; Radiation Injuries/*complications/*therapy ; Sex Factors ; Specific Pathogen-Free Organisms ; }, abstract = {Safe and effective regimens are still needed given the risk of radiation toxicity from iatrogenic irradiation. The gut microbiota plays an important role in radiation damage. Diet has emerged as a key determinant of the intestinal microbiome signature and function. In this report, we investigated whether a 30% caloric restriction (CR) diet may ameliorate radiation enteritis and hematopoietic toxicity. Experimental mice were either fed ad libitum (AL) or subjected to CR preconditioning for 10 days and then exposed to total body irradiation (TBI) or total abdominal irradiation (TAI). Gross examinations showed that short-term CR pretreatment restored hematogenic organs and improved the intestinal architecture in both male and female mice. Intriguingly, CR preconditioning mitigated radiation-induced systemic and enteric inflammation in female mice, while gut barrier function improved in irradiated males. 16S rRNA high-throughput sequencing showed that the frequency of pro-inflammatory microbes, including Helicobacter and Desulfovibrionaceae, was reduced in female mice after 10 days of CR preconditioning, while an enrichment of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibaculum, Clostridiales, and Lactobacillus, was observed in males. Using fecal microbiota transplantation (FMT) or antibiotic administration to alter the gut microbiota counteracted the short-term CR-elicited radiation tolerance of both male and female mice, further indicating that the radioprotection of a 30% CR diet depends on altering the gut microbiota. Together, our findings provide new insights into CR in clinical applications and indicate that a short-term CR diet prior to radiation modulates sex-specific gut microbiota configurations, protecting male and female mice against the side effects caused by radiation challenge.}, }
@article {pmid34319520, year = {2021}, author = {El-Sayed, A and Aleya, L and Kamel, M}, title = {Microbiota and epigenetics: promising therapeutic approaches?.}, journal = {Environmental science and pollution research international}, volume = {28}, number = {36}, pages = {49343-49361}, pmid = {34319520}, issn = {1614-7499}, mesh = {Fecal Microbiota Transplantation ; *Microbiota ; Prebiotics ; *Probiotics ; *Synbiotics ; }, abstract = {The direct/indirect responsibility of the gut microbiome in disease induction in and outside the digestive tract is well studied. These results are usually from the overpopulation of certain species on the cost of others, interaction with beneficial microflora, interference with normal epigenetic control mechanisms, or suppression of the immune system. Consequently, it is theoretically possible to cure such disorders by rebalancing the microbiome inside our bodies. This can be achieved by changing the lifestyle pattern and diet or by supplementation with beneficial bacteria or their metabolites. Various approaches have been explored to manipulate the normal microbial inhabitants, including nutraceutical, supplementations with prebiotics, probiotics, postbiotics, synbiotics, and antibiotics, or through microbiome transplantation (fecal, skin, or vaginal microbiome transplantation). In the present review, the interaction between the microbiome and epigenetics and their role in disease induction is discussed. Possible future therapeutic approaches via the reestablishment of equilibrium in our internal micro-ecosystem are also highlighted.}, }
@article {pmid34316559, year = {2020}, author = {Merrick, B and Allen, L and Masirah M Zain, N and Forbes, B and Shawcross, DL and Goldenberg, SD}, title = {Regulation, risk and safety of Faecal Microbiota Transplant.}, journal = {Infection prevention in practice}, volume = {2}, number = {3}, pages = {100069}, pmid = {34316559}, issn = {2590-0889}, abstract = {From its origins as a left-field, experimental, and even "maverick" intervention, faecal microbiota transplantation (FMT) is now a well-recognised, accepted, and potentially life-saving therapeutic strategy, for the management of recurrent Clostridiodes difficile infection (rCDI). It is being investigated as a treatment for a growing number of diseases including hepatic encephalopathy and eradication of antimicrobial resistant organisms, and the list of indications will likely expand in the future. There is no universally accepted definition of what FMT is, and its mechanism of action remains incompletely understood; this has likely contributed to the breadth of approaches to regulation depending on interpretation. In the UK FMT is considered a medicinal product, in North America, a biological product, whereas in parts of Europe, it is considered a human cell/tissue product. Regulation seeks to improve quality and safety, however, lack of standardisation creates confusion, and overly restrictive regulation may hamper widespread access and discourage research using FMT. FMT is generally considered safe, especially if rigorous donor screening and testing is conducted. Most short-term risks are associated with the delivery method (e.g. colonoscopy). Longer term risks are less well described but longitudinal follow-up of treated cohorts is in place to assess for this, and no signal towards harm has been found to date. Rarely it has been associated with adverse outcomes including the transmission of antibiotic resistant bacteria, and even death. It is vital patients undergoing FMT are well informed to the currently appreciated risks and benefits before proceeding.}, }
@article {pmid34313540, year = {2021}, author = {Trikha, SRJ and Lee, DM and Ecton, KE and Wrigley, SD and Vazquez, AR and Litwin, NS and Thomas, KN and Wei, Y and Battson, ML and Johnson, SA and Kuhn, KA and Colgan, SP and Gentile, CL and Weir, TL}, title = {Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1940791}, pmid = {34313540}, issn = {1949-0984}, support = {R01 DK104713/DK/NIDDK NIH HHS/United States ; R01 HL144611/HL/NHLBI NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Animals ; Cohort Studies ; Disease Models, Animal ; Female ; *Gastrointestinal Microbiome ; Germ-Free Life ; Glucose Intolerance/*etiology/*physiopathology ; Healthy Volunteers ; Humans ; Male ; Mice ; Middle Aged ; Obesity/*complications/*microbiology ; Vascular Diseases/*etiology/*physiopathology ; }, abstract = {Recent preclinical data suggest that alterations in the gut microbiota may be an important factor linking obesity to vascular dysfunction, an early sign of cardiovascular disease. The purpose of this study was to begin translation of these preclinical data by examining whether vascular phenotypes in humans are transmissible through the gut microbiota. We hypothesized that germ-free mice colonized with gut microbiota from obese individuals would display diminished vascular function compared to germ-free mice receiving microbiota from lean individuals.We transplanted fecal material from obese and lean age-and sex-matched participants with disparate vascular function to germ-free mice. Using Principle Component Analysis, the microbiota of colonized mice separated by donor group along the first principle component, accounting for between 70-93% of the total variability in the dataset. The microbiota of mice receiving transplants from lean individuals was also characterized by increased alpha diversity, as well as increased relative abundance of potentially beneficial bacteria, including Bifidobacterium, Lactobacillus, and Bacteroides ovatis. Endothelium-dependent dilation, aortic pulse wave velocity and glucose tolerance were significantly altered in mice receiving microbiota from the obese donor relative to those receiving microbiota from the lean donor or those remaining germ-free.These data indicate that the obesity-associated human gut microbiota is sufficient to alter the vascular phenotype in germ-free mice in the absence of differences in body weight or dietary manipulation, and provide justification for future clinical trials to test the efficacy of microbiota-targeted therapies in the prevention or treatment of cardiovascular disease.}, }
@article {pmid34312355, year = {2021}, author = {Jo, HG and Seo, GS}, title = {[Efficacy and Safety of Fecal Microbiota Transplantation and Prospect of Microbe-based Therapies for Inflammatory Bowel Disease].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {78}, number = {1}, pages = {31-36}, doi = {10.4166/kjg.2021.089}, pmid = {34312355}, issn = {2233-6869}, mesh = {Clostridium Infections ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; *Inflammatory Bowel Diseases/therapy ; Prospective Studies ; }, abstract = {The use of 5-ASA, immunomodulators, biologics, and small molecule drugs are the main treatment for inflammatory bowel disease (IBD), however, fecal microbiota transplantation (FMT) is also drawing attention as a treatment to improve intestinal dysbiosis by transplantaing normal human stool into patients with IBD. FMT demonstrates relatively good effects in inducing clinical remission in IBD, but unlike Clostridium difficile infection, multiple FMT can enhance the clinical effect. There are no reports of the long-term effectiveness and safety of FMT conducted in IBD yet, therefore, well-designed, prospective studies will be needed. Gut microbiota can affect inflammatory response, intestinal barrier function, and host metabolism, so microbe-based therapies are likely to be a new treatment option for IBD. The deeper the understanding of microbe products or effectors, the more likely it is to provide personalized therapy in IBD.}, }
@article {pmid34308364, year = {2020}, author = {Huang, YW and Pan, P and Echeveste, CE and Wang, HT and Oshima, K and Lin, CW and Yearsley, M and Xiao, J and Chen, J and Sun, C and Yu, J and Wang, LS}, title = {Transplanting fecal material from wild-type mice fed black raspberries alters the immune system of recipient mice.}, journal = {Food frontiers}, volume = {1}, number = {3}, pages = {253-259}, pmid = {34308364}, issn = {2643-8429}, support = {R01 AI129582/AI/NIAID NIH HHS/United States ; R01 CA148818/CA/NCI NIH HHS/United States ; R01 CA185301/CA/NCI NIH HHS/United States ; R01 NS106170/NS/NINDS NIH HHS/United States ; }, abstract = {By constantly stimulating intestinal immunity, gut microbes play important regulatory roles, and their possible involvement in human physical and mental disorders beyond intestinal diseases suggests the importance of maintaining homeostasis in the gut microbiota. Both transplantation of fecal microbiota and dietary interventions have been shown to restore microbial homeostasis in recipients. In the current study with wild-type mice, we combined these two approaches to determine if transplanting fecal material from mice fed black raspberries (BRB, 5%) altered recipients' immune system. The donors received a control or 5% BRB diet, and fecal transplantation was performed every other day 15 times into recipients fed control diet. Afterward, we used flow cytometry to analyze populations of CD3[+] T, CD4[+] T, CD8[+] T cells, and NK cells among bone marrow cells, splenocytes, and peripheral blood mononuclear cells (PBMCs) collected from the recipients. We found that BRB-fecal material that contained both fecal microbiota and their metabolites increased NK cell populations among bone marrow cells, splenocytes, and PBMCs, and raised levels of CD8[+] T cells in splenocytes. Our findings suggest that fecal transplantation can modulate the immune system and might therefore be valuable for managing a range of physical and mental disorders.}, }
@article {pmid34307618, year = {2021}, author = {Kim, BS and Park, SY and Kim, DH and Kim, NI and Yoon, JH and Ju, JK and Park, CH and Kim, HS and Choi, SK}, title = {Cytomegalovirus colitis induced segmental colonic hypoganglionosis in an immunocompetent patient: A case report.}, journal = {World journal of clinical cases}, volume = {9}, number = {20}, pages = {5631-5636}, pmid = {34307618}, issn = {2307-8960}, abstract = {BACKGROUND: Cytomegalovirus (CMV) colitis is usually seen in immunocompromised patients with risk factors such as human immunodeficiency virus infection, solid organ transplant, inflammatory bowel disease, or malignancy. Therefore, many clinicians usually do not consider the possibility of CMV colitis in immunocompetent patients. We reported a rare case of segmental colonic hypoganglionosis associated with CMV colitis in an immunocompetent patient.<br><br>CASE SUMMARY: A 48-year-old woman with no underlying disease was admitted to our hospital for severe abdominal pain and constipation. Computed tomography of the abdomen showed diffuse dilatation of the small intestine and the entire colon. Initial sigmoidoscopic findings and result of polymerase chain reaction (PCR) for CMV revealed the compatible findings of CMV colitis, the patient was treated with intravenous ganciclovir. After treatment, sigmoidoscopic findings and CMV PCR results improved. However the patient continued to suffered from constipation. Eight months after the initial admission, patient visited the emergency department with severe abdominal pain and imaging revealed aggravation of fecal impaction and bowel dilatation. We performed subtotal colectomy to control patient's symptom. Histological examination of the resected specimen showed significantly reduced number of mature ganglion cells in the sigmoid colon compared to that in the proximal colon.<br><br>CONCLUSION: Our case demonstrates that CMV colitis can develop even in patients with no other underlying disease, and that CMV colitis can be one of the causes for developing colonic hypoganglionosis.}, }
@article {pmid34305883, year = {2021}, author = {Malczewski, AB and Ketheesan, N and Coward, JIG and Navarro, S}, title = {Enhancing Checkpoint Inhibitor Therapy in Solid Tissue Cancers: The Role of Diet, the Microbiome &amp; Microbiome-Derived Metabolites.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {624434}, pmid = {34305883}, issn = {1664-3224}, mesh = {Animals ; Bacteria/metabolism ; Diet/adverse effects/*methods ; Dysbiosis/complications ; Gastrointestinal Microbiome/*drug effects/immunology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Immunomodulation ; Life Style ; Metabolome/drug effects/*immunology ; Mice ; Neoplasms/*drug therapy/immunology ; }, abstract = {Host immunity plays a central role in the regulation of anti-tumour responses during checkpoint inhibitor therapy (CIT). The mechanisms involved in long lasting remission remain unclear. Animal studies have revealed that the microbiome influences the host immune response. This is supported by human studies linking a higher microbial richness and diversity with enhanced responses to CIT. This review focuses on the role of diet, the microbiome and the microbiome-derived metabolome in enhancing responses to current CIT in solid tissue cancers. The Western diet has been associated with dysbiosis, inflammation and numerous metabolic disorders. There is preliminary evidence that lifestyle factors including a high fibre diet are associated with improved responses to CIT via a potential effect on the microbiota. The mechanisms through which the microbiota may regulate long-term immunotherapy responses have yet to be determined, although bacterial-metabolites including short chain fatty acids (SCFAs) are recognized to have an impact on T cell differentiation, and may affect T effector/regulatory T cell balance. SCFAs were also shown to enhance the memory potential of activated CD8 T cells. Many therapeutic approaches including dietary manipulation and fecal transplantation are currently being explored in order to enhance immunotherapy responses. The microbiome-derived metabolome may be one means through which bacterial metabolic products can be monitored from the start of treatment and could be used to identify patients at risk of poor immunotherapy responses. The current review will discuss recent advances and bring together literature from related fields in nutrition, oncology and immunology to discuss possible means of modulating immunity to improve responses to current CIT.}, }
@article {pmid34304786, year = {2021}, author = {Singh, P and Lembo, A}, title = {Emerging Role of the Gut Microbiome in Irritable Bowel Syndrome.}, journal = {Gastroenterology clinics of North America}, volume = {50}, number = {3}, pages = {523-545}, doi = {10.1016/j.gtc.2021.03.003}, pmid = {34304786}, issn = {1558-1942}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {Advances in bioinformatics have facilitated investigation of the role of gut microbiota in patients with irritable bowel syndrome (IBS). This article describes the evidence from epidemiologic and clinical observational studies highlighting the link between IBS and gut microbiome by investigating postinfection IBS, small intestinal bacterial overgrowth, and microbial dysbiosis. It highlights the effects of gut microbiota on mechanisms implicated in the pathophysiology of IBS, including gut-brain axis, visceral hypersensitivity, motility, epithelial barrier, and immune activation. In addition, it summarizes the current evidence on microbiome-guided therapies in IBS, including probiotics, antibiotics, diet, and fecal microbiota transplant.}, }
@article {pmid34303637, year = {2022}, author = {Iida, Y and Honda, K and Iida, R and Saitou, H and Munemoto, Y and Tanaka, A and Tanaka, H}, title = {Modified open posterior internal sphincterotomy with sliding skin graft for chronic anal fissure and anal stenosis: Low recurrence rate and no serious faecal incontinence postoperative complication.}, journal = {Journal of visceral surgery}, volume = {159}, number = {4}, pages = {267-272}, doi = {10.1016/j.jviscsurg.2021.07.002}, pmid = {34303637}, issn = {1878-7886}, mesh = {Adult ; Aged ; Anal Canal/surgery ; Chronic Disease ; Constriction, Pathologic/etiology/surgery ; *Fecal Incontinence/etiology/surgery ; *Fissure in Ano/complications/surgery ; Humans ; *Lateral Internal Sphincterotomy/adverse effects ; Middle Aged ; Postoperative Complications/epidemiology/etiology/surgery ; Skin Transplantation/adverse effects ; Treatment Outcome ; }, abstract = {AIM: Lateral internal sphincterotomy (LIS) remains a standard for chronic anal fissure even though other surgical techniques have shown high efficacy. Faecal incontinence is a well-documented complication of LIS. We devised modified open posterior internal sphincterotomy (m-OPIS) with sliding skin graft (SSG), which is a combined procedure of OPIS and anal advancement flap. The aim of this study is to evaluate m-OPIS+SSG.<br><br>METHODS: This was a retrospective, observational, single-arm study. m-OPIS+SSG was performed for chronic anal fissure and anal stenosis. m-OPIS involved incision of the internal sphincter muscle at the posterior midline until four fingers could be passed. The incision wound was closed by anastomosis of the anoderm and skin. Then, an arcuate skin incision was created and the skin graft was advanced into the anal canal. Follow-up was conducted by clinical consultation and telephone interview. Faecal continence was assessed by Cleveland Clinic Faecal Incontinence (CCFI) score.<br><br>RESULTS: m-OPIS+SSG was performed in 143 patients. The mean patient age was 50&#xb1;16 years. The success and overall recurrence rates after m-OPIS+SSG were 99% and 0.7%, respectively, with a median follow-up period of 16.3 years. One patient developed incontinence with liquid stools once during the 6-month period. None of the other patients suffered permanent faecal incontinence postoperatively. The postoperative CCFI score was 0.5&#xb1;0.9.<br><br>CONCLUSIONS: We consider m-OPIS+SSG as one of the efficacious options of procedure for chronic anal fissure and anal stenosis, owing to its high success rate, low recurrence rate and no postoperative complication of serious faecal incontinence.}, }
@article {pmid34303438, year = {2021}, author = {Amin, K and Choksi, V and Farouk, SS and Sparks, MA}, title = {Diarrhea in a Patient With Combined Kidney-Pancreas Transplant.}, journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation}, volume = {78}, number = {2}, pages = {A13-A16}, doi = {10.1053/j.ajkd.2021.01.023}, pmid = {34303438}, issn = {1523-6838}, mesh = {Caliciviridae Infections/complications/*diagnosis/virology ; Diabetes Mellitus, Type 1/*surgery ; Diagnosis, Differential ; Diarrhea/*etiology/therapy ; Disease Progression ; Drug Tapering ; Feces/chemistry ; Fluid Therapy ; Gastroenteritis/complications/*diagnosis/virology ; Glucocorticoids/therapeutic use ; Graft Rejection/prevention &amp; control ; Humans ; Immunosuppressive Agents/adverse effects ; Kidney Failure, Chronic/*surgery ; *Kidney Transplantation ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction ; Mycophenolic Acid/adverse effects ; *Pancreas Transplantation ; Prednisone/therapeutic use ; Sapovirus/*genetics ; Tacrolimus/adverse effects ; }, }
@article {pmid34302959, year = {2022}, author = {Wahid, M and Dar, SA and Jawed, A and Mandal, RK and Akhter, N and Khan, S and Khan, F and Jogaiah, S and Rai, AK and Rattan, R}, title = {Microbes in gynecologic cancers: Causes or consequences and therapeutic potential.}, journal = {Seminars in cancer biology}, volume = {86}, number = {Pt 2}, pages = {1179-1189}, doi = {10.1016/j.semcancer.2021.07.013}, pmid = {34302959}, issn = {1096-3650}, mesh = {Humans ; Female ; Vagina/microbiology ; Lactobacillus ; *Microbiota/genetics ; *Genital Neoplasms, Female/etiology/therapy ; *Probiotics/therapeutic use ; }, abstract = {Gynecologic cancers, starting in the reproductive organs of females, include cancer of cervix, endometrium, ovary commonly and vagina and vulva rarely. The changes in the composition of microbiome in gut and vagina affect immune and metabolic signaling of the host cells resulting in chronic inflammation, angiogenesis, cellular proliferation, genome instability, epithelial barrier breach and metabolic dysregulation that may lead to the onset or aggravated progression of gynecologic cancers. While microbiome in gynecologic cancers is just at horizon, certain significant microbiome signature associations have been found. Cervical cancer is accompanied with high loads of human papillomavirus, Fusobacteria and Sneathia species; endometrial cancer is reported to have presence of Atopobium vaginae and Porphyromonas species and significantly elevated levels of Proteobacteria and Firmicutes phylum bacteria, with Chlamydia trachomatis, Lactobacillus and Mycobacterium reported in ovarian cancer. Balancing microbiome composition in gynecologic cancers has the potential to be used as a therapeutic target. For example, the Lactobacillus species may play an important role in blocking adhesions of incursive pathogens to vaginal epithelium by lowering the pH, producing bacteriocins and employing competitive exclusions. The optimum or personalized balance of the microbiota can be maintained using pre- and probiotics, and fecal microbiota transplantations loaded with specific bacteria. Current evidence strongly suggest that a healthy microbiome can train and trigger the body's immune response to attack various gynecologic cancers. Furthermore, microbiome modulations can potentially contribute to improvements in immuno-oncology therapies.}, }
@article {pmid34301806, year = {2021}, author = {Xie, Y and Song, L and Yang, J and Tao, T and Yu, J and Shi, J and Jin, X}, title = {Small intestinal flora graft alters fecal flora, stool, cytokines and mood status in healthy mice.}, journal = {Life science alliance}, volume = {4}, number = {9}, pages = {}, pmid = {34301806}, issn = {2575-1077}, mesh = {*Affect ; Animals ; *Behavior, Animal ; Biomarkers ; Body Weight ; Cytokines/blood/*metabolism ; Drinking ; Eating ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Male ; Metagenome ; Metagenomics ; Mice ; }, abstract = {Fecal microbiota transplantation is widely used. Large intestinal microbiota (LIM) is more similar to fecal microbiota than small intestinal microbiota (SIM). The SIM communities are very different from those of LIM. Therefore, SIM transplantation (SIMT) and LIM transplantation (LIMT) might exert different influences. Here, healthy adult male C57Bl/6 mice received intragastric SIMT, LIMT, or sterile PBS administration. Microbiota graft samples were collected from small/large intestine of healthy mice of the same age, sex, and strain background. Compared with PBS treatment, SIMT increased pellet number, stool wet weight, and stool water percentage; induced a fecal microbiota profile shift toward the microbial composition of the SIM graft; induced a systemic anti-inflammatory cytokines profile; and ameliorated depressive-like behaviors in recipients. LIMT, however, induced merely a slight alteration in fecal microbial composition and no significant influence on the other aspects. In sum, SIMT, rather than LIMT, affected defecation features, fecal microbial composition, cytokines profile, and depressive-like behaviors in healthy mice. This study reveals the different effects of SIMT and LIMT, providing an interesting clue for further researches involving gut microbial composition change.}, }
@article {pmid34301799, year = {2021}, author = {Junius, S and Mavrogiannis, AV and Lemaitre, P and Gerbaux, M and Staels, F and Malviya, V and Burton, O and Gergelits, V and Singh, K and Tito Tadeo, RY and Raes, J and Humblet-Baron, S and Liston, A and Schlenner, SM}, title = {Unstable regulatory T cells, enriched for naïve and Nrp1[neg] cells, are purged after fate challenge.}, journal = {Science immunology}, volume = {6}, number = {61}, pages = {}, doi = {10.1126/sciimmunol.abe4723}, pmid = {34301799}, issn = {2470-9468}, support = {BBS/E/B/000C0427/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/B/000C0428/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adoptive Transfer ; Animals ; Cytokines/blood ; Feces/chemistry ; Female ; Forkhead Transcription Factors/genetics/immunology ; Gastrointestinal Microbiome/genetics ; Male ; Mice, Transgenic ; Neuropilin-1/immunology ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Regulatory T cells (Tregs) are indispensable for the control of immune homeostasis and have clinical potential as a cell therapy for treating autoimmunity. Tregs can lose expression of the lineage-defining Foxp3 transcription factor and acquire effector T cell (Teff) characteristics, a process referred to as Treg plasticity. The extent and reversibility of such plasticity during immune responses remain unknown. Here, using a murine genetic fate-mapping system, we show that Treg stability is maintained even during exposure to a complex microbial/antigenic environment. Furthermore, we demonstrate that the observed plasticity of Tregs after adoptive transfer into a lymphopenic environment is a property limited to only a subset of the Treg population, with the nonconverting majority of Tregs being resistant to plasticity upon secondary stability challenge. The unstable Treg fraction is a complex mixture of phenotypically distinct Tregs, enriched for naïve and neuropilin-1-negative Tregs, and includes peripherally induced Tregs and recent thymic emigrant Tregs These results suggest that a "purging" process can be used to purify stable Tregs that are capable of robust fate retention, with potential implications for improving cell transfer therapy.}, }
@article {pmid34301274, year = {2021}, author = {Lin, X and Liu, Y and Ma, L and Ma, X and Shen, L and Ma, X and Chen, Z and Chen, H and Li, D and Su, Z and Chen, X}, title = {Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {317}, pmid = {34301274}, issn = {1479-5876}, mesh = {Animals ; Constipation ; Cytokines ; Dysbiosis/complications ; *Encephalomyelitis, Autoimmune, Experimental/complications ; Female ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Quality of Life ; Th17 Cells ; }, abstract = {BACKGROUND: Constipation is a common gastrointestinal dysfunction which has a potential impact on people's immune state and their quality of life. Here we investigated the effects of constipation on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).<br><br>METHODS: Constipation was induced by loperamide in female C57BL/6 mice. The alternations of gut microbiota, permeability of intestinal barrier and blood-brain barrier, and histopathology of colon were assessed after constipation induction. EAE was induced in the constipation mice. Fecal microbiota transplantation (FMT) was performed from constipation mice into microbiota-depleted mice. Clinical scores, histopathology of inflammation and demyelination, Treg/Th17 and Treg17/Teff17 imbalance both in the peripheral lymphatic organs and central nervous system, cytokines include TGF-&#x3b2;, GM-CSF, IL-10, IL-17A, IL-17F, IL-21, IL-22, and IL-23 in serum were assessed in different groups.<br><br>RESULTS: Compared with the vehicle group, the constipation mice showed gut microbiota dysbiosis, colon inflammation and injury, and increased permeability of intestinal barrier and blood-brain barrier. We found that the clinical and pathological scores of the constipation EAE mice were severer than that of the EAE mice. Compared with the EAE mice, the constipation EAE mice showed reduced percentage of Treg and Treg17 cells, increased percentage of Th17 and Teff17 cells, and decreased ratio of Treg/Th17 and Treg17/Teff17 in the spleen, inguinal lymph nodes, brain, and spinal cord. Moreover, the serum levels of TGF-&#x3b2;, IL-10, and IL-21 were decreased while the GM-CSF, IL-17A, IL-17F, IL-22, and IL-23 were increased in the constipation EAE mice. In addition, these pathological processes could be transferred via their gut microbiota.<br><br>CONCLUSIONS: Our results verified that constipation induced gut microbiota dysbiosis exacerbated EAE via aggravating Treg/Th17 and Treg17/Teff17 imbalance and cytokines disturbance in C57BL/6 mice.}, }
@article {pmid34295835, year = {2021}, author = {Wang, X and Tang, Q and Hou, H and Zhang, W and Li, M and Chen, D and Gu, Y and Wang, B and Hou, J and Liu, Y and Cao, H}, title = {Gut Microbiota in NSAID Enteropathy: New Insights From Inside.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {679396}, pmid = {34295835}, issn = {2235-2988}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; *Gastrointestinal Microbiome ; Humans ; *Intestinal Diseases/chemically induced ; Intestinal Mucosa ; *Microbiota ; *Probiotics ; }, abstract = {As a class of the commonly used drugs in clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) can cause a series of adverse events including gastrointestinal injuries. Besides upper gastrointestinal injuries, NSAID enteropathy also attracts attention with the introduction of capsule endoscopy and double balloon enteroscopy. However, the pathogenesis of NSAID enteropathy remains to be entirely clarified. Growing evidence from basic and clinical studies presents that gut microbiota is a critical factor in NSAID enteropathy progress. We have reviewed the recent data about the interplay between gut microbiota dysbiosis and NSAID enteropathy. The chronic medication of NSAIDs could change the composition of the intestinal bacteria and aggravate bile acids cytotoxicity. Meanwhile, NSAIDs impair the intestinal barrier by inhibiting cyclooxygenase and destroying mitochondria. Subsequently, intestinal bacteria translocate into the mucosa, and then lipopolysaccharide released from gut microbiota combines to Toll-like receptor 4 and induce excessive production of nitric oxide and pro-inflammatory cytokines. Intestinal injuries present in the condition of intestinal inflammation and oxidative stress. In this paper, we also have reviewed the possible strategies of regulating gut microbiota for the management of NSAID enteropathy, including antibiotics, probiotics, prebiotics, mucosal protective agents, and fecal microbiota transplant, and we emphasized the adverse effects of proton pump inhibitors on NSAID enteropathy. Therefore, this review will provide new insights into a better understanding of gut microbiota in NSAID enteropathy.}, }
@article {pmid34289768, year = {2021}, author = {Park, SH and Lee, JH and Shin, J and Kim, JS and Cha, B and Lee, S and Kwon, KS and Shin, YW and Choi, SH}, title = {Cognitive function improvement after fecal microbiota transplantation in Alzheimer's dementia patient: a case report.}, journal = {Current medical research and opinion}, volume = {37}, number = {10}, pages = {1739-1744}, doi = {10.1080/03007995.2021.1957807}, pmid = {34289768}, issn = {1473-4877}, mesh = {Aged, 80 and over ; *Alzheimer Disease/therapy ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Cognition ; Fecal Microbiota Transplantation ; Feces ; Female ; Humans ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although it is known that the gut microbiome is linked with cognitive function, whether FMT may lead to cognitive improvement in patients with neurodegenerative disorders remains to be elucidated. We present the case of a 90-year-old woman with Alzheimer's dementia and severe CDI who underwent FMT. Cognitive function testing (Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating assessment) was performed one month before FMT and one week and one month after FMT. We collected the patients' fecal samples before FMT and 3 weeks after FMT to compare the microbiota composition. The 16S rRNA gene amplicons were analyzed using the QIIME2 platform (version 2020.2) and the Phyloseq R package. The linear discriminant analysis effect size was performed to determine the taxonomic difference between pre- and post-FMT. Functional biomarker analysis using the Kruskal-Wallis H test was performed between the pre- and post-FMT. The cognitive function tests after FMT showed an improvement compared to the tests before the procedure. FMT changed the microbiota composition in recipient feces. We found that the genera were reported to be associated with cognitive function. In addition, short-chain fatty acids were found to be significantly different between before and after FMT. This finding suggests the presence of an association between the gut microbiome and cognitive function. Further, it emphasizes the need for clinical awareness regarding the effect of FMT on the brain-gut-microbiome axis and its potential as a therapy for patients with dementia.}, }
@article {pmid34289209, year = {2021}, author = {Ding, G and Gong, Q and Ma, J and Liu, X and Wang, Y and Cheng, X}, title = {Immunosuppressive activity is attenuated by Astragalus polysaccharides through remodeling the gut microenvironment in melanoma mice.}, journal = {Cancer science}, volume = {112}, number = {10}, pages = {4050-4063}, pmid = {34289209}, issn = {1349-7006}, support = {19401901600//the Shanghai Science and Technology Action Innovation Plan/ ; 81973543//National Natural Science Foundation of China/ ; YB-20-08//the Education and Scientific Research Projects of 2021 in the 14th Five Year Plan of National Higher Education of Traditional Chinese Medicine/ ; }, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Arginase/drug effects/metabolism ; Astragalus Plant/*chemistry ; Bifidobacterium/drug effects/metabolism ; CD8-Positive T-Lymphocytes/*immunology ; Drug Combinations ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/genetics/immunology/physiology ; Immune Tolerance ; Interleukin-10/metabolism ; Interleukin-1beta/blood ; Interleukin-6/blood ; Lactobacillus/drug effects ; Male ; Melanoma/*drug therapy/immunology/pathology ; Mice ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells/*drug effects/immunology/metabolism ; Polysaccharides/*pharmacology ; RNA, Ribosomal, 16S/analysis ; Transforming Growth Factor beta/drug effects/metabolism ; Tumor Microenvironment/immunology ; }, abstract = {Astragalus polysaccharides (APS), the main effective component of Astragalus membranaceus, can inhibit tumor growth, but the underlying mechanisms remain unclear. Previous studies have suggested that APS can regulate the gut microenvironment, including the gut microbiota and fecal metabolites. In this work, our results showed that APS could control tumor growth in melanoma-bearing mice. It could reduce the number of myeloid-derived suppressor cells (MDSC), as well as the expression of MDSC-related molecule Arg-1 and cytokines IL-10 and TGF-β, so that CD8[+] T cells could kill tumor cells more effectively. However, while APS were administered with an antibiotic cocktail (ABX), MDSC could not be reduced, and the growth rate of tumors was accelerated. Consistent with the changes in MDSC, the serum levels of IL-6 and IL-1β were lowest in the APS group. Meanwhile, we found that fecal suspension from mice in the APS group could also reduce the number of MDSC in tumor tissues. These results revealed that APS regulated the immune function in tumor-bearing mice through remodeling the gut microbiota. Next, we focused on the results of 16S rRNA, which showed that APS significantly regulated most microorganisms, such as Bifidobacterium pseudolongum, Lactobacillus johnsonii and Lactobacillus. According to the Spearman analysis, the changes in abundance of these microorganisms were related to the increase of metabolites like glutamate and creatine, which could control tumor growth. The present study demonstrates that APS attenuate the immunosuppressive activity of MDSC in melanoma-bearing mice by remodeling the gut microbiota and fecal metabolites. Our findings reveal the therapeutic potential of APS to control tumor growth.}, }
@article {pmid34286501, year = {2021}, author = {de Belvis, AG and Fratini, A and Angioletti, C and Morsella, A and Ruggeri, R and Pepe, G and Ianiro, G and Settanni, C and Gasbarrini, A and Cammarota, G}, title = {How to define a quadruple aim framework to assess value in critical pathway of the patients with Clostridioides difficile infection.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {13}, pages = {4597-4610}, doi = {10.26355/eurrev_202107_26252}, pmid = {34286501}, issn = {2284-0729}, mesh = {Clostridioides difficile/pathogenicity ; Clostridium Infections/complications/epidemiology/microbiology/*therapy ; Critical Pathways/*standards ; Delphi Technique ; Evidence-Based Medicine/methods/*standards ; Fecal Microbiota Transplantation/*standards ; Humans ; Length of Stay/statistics &amp; numerical data ; Practice Guidelines as Topic ; Recurrence ; Treatment Outcome ; }, abstract = {OBJECTIVE: The study aims to define the set of Key Performance Indicators (KPIs) required to assess the Value delivered by managing patients with Clostridioides difficile infection through a Critical Pathway. We used the quadruple aim Value-Based approach, and we validated the set of KPIs with the Delphi method.<br><br>MATERIALS AND METHODS: The study focuses on patients on board a Critical Pathway on Clostridioides difficile Infection and targeted towards a Fecal Microbiota Transplantation (FMT). FMT has been used to successfully treat recurrent Clostridium difficile infection. A two-round e-Delphi survey collecting data was conducted in 2019-2020 to validate the Value-Based evaluation tool. The Value-Based criteria taken into account are Clinical Outcomes, Experience of Care, Per-capita cost, Physician's burnout.<br><br>RESULTS: The two rounds led to the validation of 50 items, and four primary clinical outcomes (Mortality rate, length of stay, readmission and complications related to the illness).<br><br>CONCLUSIONS: The evaluation tool included is validated in its totality and can provide a comprehensive overview of the Value created by the Critical pathway for patients with Clostridioides difficile. We can extend the approach illustrated in this study can also to evaluate other Critical pathways.}, }
@article {pmid34283837, year = {2021}, author = {Velasco, C and Dunn, C and Sturdy, C and Izda, V and Martin, J and Rivas, A and McNaughton, J and Jeffries, MA}, title = {Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation.}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0248322}, pmid = {34283837}, issn = {1932-6203}, support = {K08 AR070891/AR/NIAMS NIH HHS/United States ; R33 AR078075/AR/NIAMS NIH HHS/United States ; P20 GM125528/GM/NIGMS NIH HHS/United States ; R61 AR078075/AR/NIAMS NIH HHS/United States ; R01 AR076440/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Wound Healing ; Mice ; Female ; Male ; *Mice, Inbred C57BL ; Ear/microbiology ; Fecal Microbiota Transplantation ; Cecum/microbiology ; }, abstract = {OBJECTIVE: Adult elastic cartilage has limited repair capacity. MRL/MpJ (MRL) mice, by contrast, are capable of spontaneously healing ear punctures. This study was undertaken to characterize microbiome differences between healer and non-healer mice and to evaluate whether this healing phenotype can be transferred via gut microbiome transplantation.<br><br>METHODS: We orally transplanted C57BL/6J (B6) mice with MRL/MpJ cecal contents at weaning and as adults (n = 57) and measured ear hole closure 4 weeks after a 2.0mm punch and compared to vehicle-transplanted MRL and B6 (n = 25) and B6-transplanted MRL (n = 20) mice. Sex effects, timing of transplant relative to earpunch, and transgenerational heritability were evaluated. In a subset (n = 58), cecal microbiomes were profiled by 16S sequencing and compared to ear hole closure. Microbial metagenomes were imputed using PICRUSt.<br><br>RESULTS: Transplantation of B6 mice with MRL microbiota, either in weanlings or adults, improved ear hole closure. B6-vehicle mice healed ear hole punches poorly (0.25&#xb1;0.03mm, mm ear hole healing 4 weeks after a 2mm ear hole punch [2.0mm-final ear hole size], mean&#xb1;SEM), whereas MRL-vehicle mice healed well (1.4&#xb1;0.1mm). MRL-transplanted B6 mice healed roughly three times as well as B6-vehicle mice, and half as well as MRL-vehicle mice (0.74&#xb1;0.05mm, P = 6.9E-10 vs. B6-vehicle, P = 5.2E-12 vs. MRL-vehicle). Transplantation of MRL mice with B6 cecal material did not reduce MRL healing (B6-transplanted MRL 1.3&#xb1;0.1 vs. MRL-vehicle 1.4&#xb1;0.1, p = 0.36). Transplantation prior to ear punch was associated with the greatest ear hole closure. Offspring of transplanted mice healed significantly better than non-transplanted control mice (offspring:0.63&#xb1;0.03mm, mean&#xb1;SEM vs. B6-vehicle control:0.25&#xb1;0.03mm, n = 39 offspring, P = 4.6E-11). Several microbiome clades were correlated with healing, including Firmicutes (R = 0.84, P = 8.0E-7), Lactobacillales (R = 0.65, P = 1.1E-3), and Verrucomicrobia (R = -0.80, P = 9.2E-6). Females of all groups tended to heal better than males (B6-vehicle P = 0.059, MRL-transplanted B6 P = 0.096, offspring of MRL-transplanted B6 P = 0.0038, B6-transplanted MRL P = 1.6E-6, MRL-vehicle P = 0.0031). Many clades characteristic of female mouse cecal microbiota vs. males were the same as clades characteristic of MRL and MRL-transplanted B6 mice vs. B6 controls, including including increases in Clostridia and reductions in Verrucomicrobia in female mice.<br><br>CONCLUSION: In this study, we found an association between the microbiome and tissue regeneration in MRL mice and demonstrate that this trait can be transferred to non-healer mice via microbiome transplantation. We identified several microbiome clades associated with healing.}, }
@article {pmid34282272, year = {2021}, author = {Malard, F and Lavelle, A and Battipaglia, G and Gaugler, B and Dulery, R and Brissot, E and Mediavilla, C and Jegou, S and Rolhion, N and Ledraa, T and Mohty, R and Sokol, H and Mohty, M}, title = {Impact of gut fungal and bacterial communities on the outcome of allogeneic hematopoietic cell transplantation.}, journal = {Mucosal immunology}, volume = {14}, number = {5}, pages = {1127-1132}, pmid = {34282272}, issn = {1935-3456}, mesh = {Adult ; Aged ; Female ; *Gastrointestinal Microbiome ; Graft vs Host Disease/diagnosis/etiology/prevention &amp; control ; *Health Impact Assessment ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Histocompatibility ; Humans ; Male ; Metagenome ; Metagenomics ; *Microbial Consortia ; Middle Aged ; *Mycobiome ; Prognosis ; Proportional Hazards Models ; Transplantation Conditioning ; Transplantation, Homologous ; Treatment Outcome ; Young Adult ; }, abstract = {Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) were previously shown to display a bacterial gut dysbiosis; however, limited data are available regarding the role of fungal microbiota in these patients. We evaluated the bacterial and fungal composition of the fecal microbiota at day 0 of alloHCT. Higher bacterial diversity was associated with an improved overall survival (OS) and disease-free survival (DFS). While fungal diversity had no impact on patient outcomes, we observed that high versus low relative abundance of Candida albicans in alloHCT patients at day 0 was associated with a significantly lower OS, DFS and graft-versus-host-free, relapse-free survival (GRFS) (p = 0.0008, p = 0.0064 and p = 0.026, respectively). While these results are limited by low patient numbers and low fungal read counts in some samples, they suggest a potentially important role for C albicans in alloHCT.}, }
@article {pmid34281401, year = {2021}, author = {Chu, ND and Crothers, JW and Nguyen, LTT and Kearney, SM and Smith, MB and Kassam, Z and Collins, C and Xavier, R and Moses, PL and Alm, EJ}, title = {Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease.}, journal = {mBio}, volume = {12}, number = {4}, pages = {e0097521}, pmid = {34281401}, issn = {2150-7511}, support = {P20 GM125498/GM/NIGMS NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/*metabolism ; Butyrates/analysis/metabolism ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Longitudinal Studies ; Metagenomics/methods ; }, abstract = {For fecal microbiota transplantation (FMT) to be successful in immune diseases like inflammatory bowel disease, it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize a recipient patient and persist in sufficient quantity and for a sufficient period of time to produce a clinical benefit. Few studies, however, have comprehensively profiled the colonization and persistence of transferred microbes along with the transfer of their microbial functions and interactions with the host immune system. Using 16S, metagenomic, and immunoglobulin A (IgA) sequencing, we analyzed hundreds of longitudinal microbiome samples from a randomized controlled trial of 12 patients with ulcerative colitis who received fecal transplant or placebo for 12 weeks. We uncovered diverse competitive dynamics among donor and patient strains, showing that persistence of transferred microbes is far from static. Indeed, one patient experienced a dramatic loss of donor bacteria 10 weeks into the trial, coinciding with a bloom of pathogenic bacteria and worsening symptoms. We evaluated the transfer of microbial functions, including desired ones, such as butyrate production, and unintended ones, such as antibiotic resistance. By profiling bacteria coated with IgA, we identified bacteria associated with inflammation and found that microbial interactions with the host immune system can be transferred across people, which could play a role in gut microbiome therapeutics for immune-related diseases. Our findings shed light on the colonization dynamics of gut microbes and their functions in the context of FMT to treat a complex disease-information that may provide a foundation for developing more-targeted therapeutics. IMPORTANCE Fecal microbiota transplantation (FMT)-transferring fecal microbes from a healthy donor to a sick patient-has shown promise for gut diseases such as inflammatory bowel disease. Unlike pharmaceuticals, however, fecal transplants are complex mixtures of living organisms, which must then interact with the microbes and immune system of the recipient. We sought to understand these interactions by tracking the microbes of 12 inflammatory bowel disease patients who received fecal transplants for 12 weeks. We uncovered a range of dynamics. For example, one patient experienced successful transfer of donor bacteria, only to lose them after 10 weeks. We similarly evaluated transfer of microbial functions, including how they interacted with the recipient's immune system. Our findings shed light on the colonization dynamics of gut microbes, as well as their functions in the context of FMT-information that may provide a critical foundation for the development of more-targeted therapeutics.}, }
@article {pmid34279746, year = {2022}, author = {Yue, Q and Cai, M and Xiao, B and Zhan, Q and Zeng, C}, title = {The Microbiota-Gut-Brain Axis and Epilepsy.}, journal = {Cellular and molecular neurobiology}, volume = {42}, number = {2}, pages = {439-453}, pmid = {34279746}, issn = {1573-6830}, support = {81601140//the national natural science foundation of china, china/ ; 81501130//the national natural science foundation of china, china/ ; 2020JJ5843//natural science foundation of hunan province, china/ ; }, mesh = {Brain/pathology ; Brain-Gut Axis ; *Diet, Ketogenic ; Dysbiosis ; *Epilepsy/pathology/therapy ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Honoured as the second genome in humans, the gut microbiota is involved in a constellation of physiological and pathological processes, including those related to the central nervous system. The communication between the gut microbiota and the brain is realized by a complex bidirectional connection, known as the "microbiota-gut-brain axis", via neuroendocrine, immunological, and direct neural mechanisms. Recent studies indicate that gut dysfunction/dysbiosis is presumably involved in the pathogenesis of and susceptibility to epilepsy. In addition, the reconstruction of the intestinal microbiome through, for example, faecal microbiota transplantation, probiotic intervention, and a ketogenic diet, has exhibited beneficial effects on drug-resistant epilepsy. The purposes of this review are to provide a brief overview of the microbiota-gut-brain axis and to synthesize what is known about the involvement of the gut microbiota in the pathogenesis and treatment of epilepsy, to bring new insight into the pathophysiology of epilepsy and to present a preliminary discussion of novel therapeutic options for epilepsy based on the gut microbiota.}, }
@article {pmid34276585, year = {2021}, author = {Dong, Y and Lu, J and Wang, T and Huang, Z and Chen, X and Ren, Z and Hong, L and Wang, H and Yang, D and Xie, H and Zhang, W}, title = {Multi-Omics Analysis Reveals Disturbance of Nanosecond Pulsed Electric Field in the Serum Metabolic Spectrum and Gut Microbiota.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {649091}, pmid = {34276585}, issn = {1664-302X}, abstract = {Nanosecond pulsed electric field (nsPEF) is a novel ablation technique that is based on high-intensity electric voltage to achieve tumour-killing effect in the target region, and increasingly considered for treating tumours of the liver, kidneys and other organs with rich blood supply. This study aims to observe effect of nsPFE treatment on serum metabolites and gut microbiota. The serum and faecal specimens of the pigs were collected pre- and post-treatment. The gut microbiota of pigs was sequenced by Illumina Miseq platform for analysing the diversity and alterations of gut microbiota. Liquid chromatography-mass spectrometry (LC-MS)-based metabonomic analysis and Pearson coefficient method were also used to construct the interaction system of different metabolites, metabolic pathways and flora. A total of 1,477 differential metabolites from the serum were identified by four cross-comparisons of different post-operative groups with the control group. In addition, an average of 636 OTUs per sample was detected. Correlation analysis also revealed the strong correlation between intestinal bacteria and differential metabolites. The nsPEF ablation of the liver results in a degree of liver damage that affects various metabolic pathways, mainly lipid metabolism, as well as gut microbiota. In conclusion, our study provided a good point for the safety and feasibility of applying nsPEF on liver through the integrated analysis of metabolomics and microbiomes, which is beneficial for the improvement of nsPEF in clinical use.}, }
@article {pmid34276224, year = {2021}, author = {Yu, C and Zhu, X and Zheng, C and Luo, Y and Wang, F and Gao, Y and Wu, H and Sun, X and Kong, X}, title = {Methyl Diet Enhanced Sepsis-Induced Mortality Through Altering Gut Microbiota.}, journal = {Journal of inflammation research}, volume = {14}, number = {}, pages = {3107-3121}, pmid = {34276224}, issn = {1178-7031}, abstract = {INTRODUCTION: Mortality of sepsis is caused by an inappropriately amplified systemic inflammatory response and bacteremia. Methyl diet has been shown to associate with greater inflammation response in different diseases. This study aimed to determine whether dietary supplementation with methyl donors affects the inflammation response and mortality in sepsis and to investigate the underlying mechanisms.<br><br>METHODS: Four-week-old male C57BL/6 mice were fed with a high-methyl diet (HMD) or a regulator diet (RD) till the experiment time. Mice septic model was induced by Cecal ligation and puncture (CLP), lipopolysaccharide (LPS), or E.coli. Inflammatory cytokine was analyzed by ELISA and qRT-PCR. Immune cell infiltration was evaluated by H&amp;E and IHC. The composition of gut microbiota was determined by 16S rRNA sequencing. The effect of gut microbiota on sepsis was further verified by fecal microbiome transplantation.<br><br>RESULTS: Our results showed that the diet riches in methyl donors exacerbated mortality, organ injury, and circulating levels of inflammatory mediators in CLP-induced septic mice model, compared to the control diet group. However, no significant differences have been observed in the inflammatory responses in the LPS-induced septic model and macrophages activation between the two groups of mice. There was a higher bacterial burden in CLP-induced HMD mice suggested that methyl diet might modulate gut microbiota. Bacterial 16S rRNA sequencing results showed that the composition of gut microbiota was altered. The high methyl donor diet reduced the abundance of Akkermansia and Lachnospiraceae, which were associated with protective effects in sepsis, in the gut. Moreover, fecal microbiome transplantation experiment showed that the transfer of feces, which obtained from high methyl diet mice, aggravated the mortality and inflammation responses in recipient mice.<br><br>DISCUSSION: Methyl diet enhanced CLP-induced septic mortality and inflammatory responses through altering the composition of gut microbiota. This result indicated that diet-based gut microbiota may be a new therapeutic strategy for sepsis patients.}, }
@article {pmid34275058, year = {2022}, author = {Feuerstadt, P and Aroniadis, OC and Svedlund, FL and Garcia, M and Stong, L and Boules, M and Khanna, S}, title = {Heterogeneity of Randomized Controlled Trials of Fecal Microbiota Transplantation in Recurrent Clostridioides difficile Infection.}, journal = {Digestive diseases and sciences}, volume = {67}, number = {7}, pages = {2763-2770}, pmid = {34275058}, issn = {1573-2568}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; *Clostridioides difficile ; *Clostridium Infections/drug therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome ; }, abstract = {INTRODUCTION: Clinical trials have demonstrated the efficacy of FMT for reduction in CDI recurrences (rCDI), but this treatment and its reporting in the literature has significant heterogeneity. Recent publications (e.g., Ramai et al. in Dig Dis Sci 2020. https://doi.org/10.1007/s10620-020-06185-7) present the clinical outcomes for different FMT methodologies. However, to understand, compare, and contextualize outcomes, this heterogeneity in methods and reporting must be understood.<br><br>METHODS: We&#xa0;performed a literature review of randomized controlled trials (RCTs) of FMT for rCDI to evaluate heterogeneity among trials. A methodical search between January 2010 and May 2019 of Medline, Embase, and Cochrane was conducted for studies investigating FMT in adults with rCDI. RCTs were evaluated for a variety of methodological and reporting criteria.<br><br>RESULTS: Eight RCTs were identified, wherein 14 different FMT preparations were considered (each with distinct protocols for processing, storage, administration, and dosing). Sample sizes were generally small, with only two studies performing FMT in more than 100 patients. Three studies used non-FMT controls (vancomycin), while the remaining compared FMT with differing routes of administration or formulations. Across the identified studies, there was no standardized manner for reporting the timing of the FMT procedure. All studies tracked adverse events; however, follow-up periods were limited.<br><br>CONCLUSIONS: Considerable variability exists among RCTs, with marked differences in study design, control groups, and outcome assessment. Lack of a standard-of-care control in many trials may impact reproducibility of FMT trial outcomes in patients with rCDI. Widespread use of FMT for rCDI is still investigational; therefore, these foundational studies provide opportunities to optimize future trials.}, }
@article {pmid34273490, year = {2021}, author = {Dong, S and Zhu, M and Wang, K and Zhao, X and Hu, L and Jing, W and Lu, H and Wang, S}, title = {Dihydromyricetin improves DSS-induced colitis in mice via modulation of fecal-bacteria-related bile acid metabolism.}, journal = {Pharmacological research}, volume = {171}, number = {}, pages = {105767}, doi = {10.1016/j.phrs.2021.105767}, pmid = {34273490}, issn = {1096-1186}, mesh = {Animals ; Anti-Inflammatory Agents/pharmacology/*therapeutic use ; Bacteria/genetics/metabolism ; Bile Acids and Salts/metabolism ; Caco-2 Cells ; Colitis/chemically induced/immunology/microbiology/*therapy ; Colon/immunology/pathology ; Dextran Sulfate ; Dysbiosis/chemically induced/immunology/microbiology/*therapy ; Fecal Microbiota Transplantation ; Feces/microbiology ; Flavonols/pharmacology/*therapeutic use ; Gastrointestinal Microbiome/drug effects ; Humans ; Interleukin-1beta/immunology ; Male ; Mice, Inbred C57BL ; Receptors, Cytoplasmic and Nuclear/immunology ; Receptors, G-Protein-Coupled/immunology ; Tumor Necrosis Factor-alpha/immunology ; Mice ; }, abstract = {Recent studies show that the nutraceutical supplement dihydromyricetin (DHM) can alleviate IBD in murine models by downregulating the inflammatory pathways. However, the molecular mechanistic link between the therapeutic efficiency of DHM, gut microbiota, and the metabolism of microbial BAs remains elusive. In this study, we explored the improvement of DHM on the dysregulated gut microbiota of mice with dextran sulfate sodium (DSS)-induced colitis. We found that DHM could markedly improve colitis symptoms, gut barrier disruption, and colonic inflammation in DSS-treated mice. In addition, bacterial 16S rDNA sequencing assay demonstrated that DHM could alleviate gut dysbiosis in mice with colitis. Furthermore, antibiotic-mediated depletion of the gut microflora and fecal microbiome transplantation (FMT) demonstrated that the therapeutic efficiency of DHM was closely associated with gut microbiota. BA-targeted metabolomics analysis revealed that DHM restored the metabolism of microbial BAs in the gastrointestinal tract during the development of colitis. DHM significantly enriched the proportion of the beneficial Lactobacillus and Akkermansia genera, which were correlated with increased gastrointestinal levels of unconjugated BAs involving chenodeoxycholic acid and lithocholic acid, enabling the BAs to activate specific receptors, such as FXR and TGR5, and maintaining intestinal integrity. Taken together, DHM could alleviate DSS-induced colitis in mice by restoring the dysregulated gut microbiota and BA metabolism, leading to improvements in intestinal barrier function and colonic inflammation. Increased microbiota-BAs-FXR/TGR5 signaling may be the potential targets of DHM in colitis. Therefore, our findings provide novel insights into the development of novel DHM-derived drugs for the management of IBD.}, }
@article {pmid34270674, year = {2022}, author = {Cappetto, CM}, title = {Erratum to: Successful use of early, repeat fecal microbiota transplantation for initial treatment of severe, refractory Clostridioides difficile colitis.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {79}, number = {7}, pages = {602}, doi = {10.1093/ajhp/zxab273}, pmid = {34270674}, issn = {1535-2900}, }
@article {pmid34269330, year = {2021}, author = {van Wessel, D and Nomden, M and Bruggink, J and de Kleine, R and Kurilshikov, A and Verkade, H and Harmsen, H and Hulscher, J}, title = {Gut Microbiota Composition of Biliary Atresia Patients Before Kasai Portoenterostomy Associates With Long-term Outcome.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {73}, number = {4}, pages = {485-490}, pmid = {34269330}, issn = {1536-4801}, mesh = {*Biliary Atresia/surgery ; Child, Preschool ; *Gastrointestinal Microbiome ; Humans ; Infant ; *Jaundice ; Portoenterostomy, Hepatic ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND AND AIMS: Biliary atresia (BA) is a cholestatic, fibro-obliterative cholangiopathy of unknown etiology. BA is primarily treated by a surgical approach, that is, the Kasai portoenterostomy (KPE), to obtain clearance of jaundice (COJ). The gut microbiota (GM) composition has been associated with the course of several cholestatic liver diseases. It is largely unknown, however, whether GM composition associates with the outcome of KPE. We compared the GM composition of BA patients and controls and assessed if GM composition before KPE was related to COJ after KPE.<br><br>METHODS: We compared feces of term-born BA patients before KPE and controls (patients undergoing inguinal hernia repair) by 16S rRNA sequencing. Composition and alpha diversity of the GM were compared between BA and controls before KPE and after KPE, between patients with COJ versus without COJ (total serum bilirubin < or &#x2265;20&#x200a;&#x3bc;mol/L <6 months post-KPE).<br><br>RESULTS: Alpha diversity was comparable between BA (n&#x200a;=&#x200a;12, age 1.6 [1.3-1.8] months) and controls (n&#x200a;=&#x200a;6, age 2.0 [1.4-2.1] months; P&#x200a;=&#x200a;0.22). Compared with controls, BA patients had lower abundances of Bifidobacteriaceae (&#x3b2;&#x200a;=&#x200a;-1.98, P&#x200a;<&#x200a;0.001) and Lachnospiraceae (&#x3b2;&#x200a;=&#x200a;-1.84, P&#x200a;=&#x200a;0.007), and higher abundances of Streptococcus (&#x3b2;&#x200a;=&#x200a;-1.13, P&#x200a;=&#x200a;0.003). The alpha diversity before KPE correlated negatively with COJ (R&#x200a;=&#x200a;-0.63, P&#x200a;=&#x200a;0.03). Lower alpha diversity pre-KPE was associated with COJ [+] (&#x3b2;logit&#x200a;=&#x200a;-0.64, P&#x200a;=&#x200a;0.04). We observed greater abundances of genus Acinetobacter (&#x3b2;&#x200a;=&#x200a;1.27, P&#x200a;=&#x200a;0.03) and family Clostridiaceae (&#x3b2;&#x200a;=&#x200a;1.45, P&#x200a;=&#x200a;0.03) and lower abundances of the family Enterobacteriaceae (genera Klebsiella (&#x3b2;&#x200a;=&#x200a;-1.21, P&#x200a;=&#x200a;0.01), Salmonella (&#x3b2;&#x200a;=&#x200a;-1.57, P&#x200a;=&#x200a;0.02)) in COJ [+] versus COJ [-].<br><br>CONCLUSIONS: The GM of BA patients before Kasai portoenterostomy associates with outcome, clearance of jaundice, suggestive of predictive, and mechanistic roles of the gut microbiota composition in bile homeostasis.}, }
@article {pmid34267748, year = {2021}, author = {Wu, J and Wang, S and Zheng, B and Qiu, X and Wang, H and Chen, L}, title = {Modulation of Gut Microbiota to Enhance Effect of Checkpoint Inhibitor Immunotherapy.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {669150}, pmid = {34267748}, issn = {1664-3224}, mesh = {Adaptive Immunity ; Animals ; Bacteria/*immunology ; Dysbiosis ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Host-Pathogen Interactions ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Immunity, Innate ; *Immunotherapy ; Neoplasms/diet therapy/*drug therapy/immunology/microbiology ; Probiotics/therapeutic use ; Treatment Outcome ; Tumor Microenvironment/*immunology ; }, abstract = {Accumulating evidence demonstrated the crucial role of gut microbiota in many human diseases, including cancer. Checkpoint inhibitor therapy has emerged as a novel treatment and has been clinically accepted as a major therapeutic strategy for cancer. Gut microbiota is related to cancer and the effect of immune checkpoint inhibitors (ICIs), and supplement with specific bacterial species can restore or enhance the responses to the ICIs. Namely, specified bacteria can serve as the biomarkers for distinguishing the patient who will respond to ICIs and determine the effectiveness of ICIs, as well as predicting the efficacy of checkpoint inhibitor immunotherapy. Regardless of the significant findings, the relationship between gut microbiota and the effect of ICIs treatment needs a more thorough understanding to provide more effective therapeutic plans and reduce treatment complication. In this review, we summarized the role of gut microbiota played in immune system and cancer. We mainly focus on the relationship between gut microbiota and the checkpoint inhibitor immunotherapy.}, }
@article {pmid34267502, year = {2021}, author = {Wang, R and Chen, T and Wang, Q and Yuan, XM and Duan, ZL and Feng, ZY and Ding, Y and Bu, F and Shi, GP and Chen, YG}, title = {Total Flavone of Abelmoschus manihot Ameliorates Stress-Induced Microbial Alterations Drive Intestinal Barrier Injury in DSS Colitis.}, journal = {Drug design, development and therapy}, volume = {15}, number = {}, pages = {2999-3016}, pmid = {34267502}, issn = {1177-8881}, mesh = {Abelmoschus/*chemistry ; Animals ; Colitis, Ulcerative/*drug therapy/physiopathology ; Depression/*drug therapy ; Dextran Sulfate ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Flavones/isolation &amp; purification/*pharmacology ; Gastrointestinal Microbiome/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Stress, Psychological/complications/drug therapy ; }, abstract = {PURPOSE: Total flavone of Abelmoschus manihot (TFA), the effective constituents extracted from Flos Abelmoschus Manihot, has been reported to inhibit inflammation. However, the effect of TFA on ulcerative colitis (UC) progression in patients with depression is unknown. The purpose of our research was to explore the anti-UC effects of TFA in the context of depression in mice with UC by regulating the gut microbiota to drive the intestinal barrier.<br><br>METHODS: In this study, chronic stress (CS) and dextran sodium sulfate (DSS) were used to induce depression and UC, respectively, in C57BL/6J mice. Fecal microbiota transplantation (FMT) was used to evaluate how treating mice modeling UC and depression with TFA effected their gut microbiota.<br><br>RESULTS: Our results showed that TFA effectively improved UC aggravated by CS. In addition, TFA treatment improved the depression-like phenotype, the disturbed gut microbiota, and the intestinal barrier function in CS mice. It is worth noting that FMT from the CS mice to the receptor group further aggravated the damage of the intestinal barrier and the disturbance of the gut microbiota in the recipient DSS mice, thus further aggravating UC, however, treatment of the intervention of TFA in the CS fecal microbiota transplant with TFA also played its therapeutic outcome.<br><br>CONCLUSION: Taken together, our results show that CS disrupts the gut microbiota, triggers intestinal barrier injury and aggravates DSS colitis, while TFA is a promising drug for the treatment of UC in patients with depression.}, }
@article {pmid34267289, year = {2021}, author = {Collins, KH and Schwartz, DJ and Lenz, KL and Harris, CA and Guilak, F}, title = {Taxonomic changes in the gut microbiota are associated with cartilage damage independent of adiposity, high fat diet, and joint injury.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {14560}, pmid = {34267289}, issn = {2045-2322}, support = {P30 AR074992/AR/NIAMS NIH HHS/United States ; P30 DK056341/DK/NIDDK NIH HHS/United States ; T32 DK007120/DK/NIDDK NIH HHS/United States ; P30 DK020579/DK/NIDDK NIH HHS/United States ; T32 DK108742/DK/NIDDK NIH HHS/United States ; }, mesh = {Adiposity ; Animals ; Bacteroidetes/genetics ; Cartilage/*physiopathology ; Diet, High-Fat/*adverse effects ; Female ; Firmicutes/genetics ; Gastrointestinal Microbiome/genetics/*physiology ; Lipodystrophy/microbiology ; Lipopolysaccharides/blood ; Male ; Meniscus/surgery ; Mice, Transgenic ; Obesity/microbiology ; Osteoarthritis/etiology/*microbiology ; RNA, Ribosomal, 16S/genetics ; Synovial Fluid/metabolism ; }, abstract = {Lipodystrophic mice are protected from cartilage damage following joint injury. This protection can be reversed by the implantation of a small adipose tissue graft. The purpose of this study was to evaluate the relationship between the gut microbiota and knee cartilage damage while controlling for adiposity, high fat diet, and joint injury using lipodystrophic (LD) mice. LD and littermate control (WT) mice were fed a high fat diet, chow diet, or were rescued with fat implantation, then challenged with destabilization of the medial meniscus surgery to induce osteoarthritis (OA). 16S rRNA sequencing was conducted on feces. MaAslin2 was used to determine associations between taxonomic relative abundance and OA severity. While serum LPS levels between groups were similar, synovial fluid LPS levels were increased in both limbs of HFD WT mice compared to all groups, except for fat transplanted animals. The Bacteroidetes:Firmicutes ratio of the gut microbiota was significantly reduced in HFD and OA-rescued animals when compared to chow. Nine novel significant associations were found between gut microbiota taxa and OA severity. These findings suggest the presence of causal relationships the gut microbiome and cartilage health, independent of diet or adiposity, providing potential therapeutic targets through manipulation of the microbiome.}, }
@article {pmid34267042, year = {2021}, author = {Jacob, JS and Ahmed, A and Cholankeril, G}, title = {The impact of alteration in gut microbiome in the pathogenesis of nonalcoholic fatty liver disease.}, journal = {Current opinion in infectious diseases}, volume = {34}, number = {5}, pages = {477-482}, pmid = {34267042}, issn = {1473-6527}, mesh = {Animals ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Liver ; *Non-alcoholic Fatty Liver Disease ; Prebiotics ; *Probiotics ; }, abstract = {PURPOSE OF REVIEW: We have increasing evidence that alterations of the intestinal microbiome have a strong influence on human health. Previous work has demonstrated the association between changes in the microbiome and metabolic risk factors. One related area of interest is the relationship between dysbiosis and nonalcoholic fatty liver disease (NAFLD), as the global prevalence of NAFLD, and its resultant complications, increases.<br><br>RECENT FINDINGS: In this review, we summarize the hypothesized pathophysiology of dysbiosis-mediated progression of NAFLD, including promotion of an inflammatory intestinal environment, increased intestinal permeability, endogenous ethanol production, short-chain fatty acid production, secondary bile acid metabolism, and choline depletion. We also review potential therapeutic interventions of the microbiome to slow or prevent NAFLD progression, including antibiotics, probiotics, prebiotics, fecal microbiota transplant, and farnesoid &#xd7; receptor agonism.<br><br>SUMMARY: Much of the evidence supporting dysbiosis-mediated NAFLD progression has been gathered in high-quality animal trials. There remains a need for additional observational and randomized controlled trials in humans to establish causality between the suspected factors and pathogenesis of NAFLD.}, }
@article {pmid34265528, year = {2021}, author = {Yang, J and Chen, W and Sun, Y and Liu, J and Zhang, W}, title = {Effects of cadmium on organ function, gut microbiota and its metabolomics profile in adolescent rats.}, journal = {Ecotoxicology and environmental safety}, volume = {222}, number = {}, pages = {112501}, doi = {10.1016/j.ecoenv.2021.112501}, pmid = {34265528}, issn = {1090-2414}, mesh = {Animals ; Cadmium/toxicity ; Feces ; Female ; *Gastrointestinal Microbiome ; Metabolomics ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Cadmium (Cd) exposure in adult animals can result in multi-organ damages and gut microbiota disturbance. However, Cd's consequences on health and gut microbiota during adolescence are obscure. In the present study, three-week-old SD rats were exposed to Cd at doses of 0, 0.25, 1, and 4 mg/kg body weight for eight weeks, and the changes of liver, kidney, and ovary function, as well as gut microbiota and its metabolomics profile, were analyzed. After transplantation of fecal bacteria from the 4 mg/kg Cd-treated group into age-matched rats (4 mg/kg-Cd recipients), the organ function and inflammatory reaction were evaluated. The results indicated that Cd perturbed gut microbiota composition, significantly decreased the abundance of Prevotella and Lachnoclostridium but increased Escherichia coli_Shigella. The fecal metabolome profile was altered and was closely correlated with some specific genera. These changes were accompanied by the inflammatory response, dyslipidemia, kidney dysfunction, and abnormal estrogen level. In 4 mg/kg-Cd recipients, the serum triglyceride (TG), lipopolysaccharide (LPS), and inflammatory cytokines were increased with the expressions of IL-1β, IL-6, TNF-α genes up-regulated in liver and kidney. Overall, this study demonstrated that Cd exposure during adolescence could cause disturbance of gut microbiota, dysfunction of liver, kidney, and ovary, which may be correlated with the activation of Cd-induced inflammatory response.}, }
@article {pmid34265258, year = {2022}, author = {Fischer, TK and Simmonds, P and Harvala, H}, title = {The importance of enterovirus surveillance in a post-polio world.}, journal = {The Lancet. Infectious diseases}, volume = {22}, number = {1}, pages = {e35-e40}, doi = {10.1016/S1473-3099(20)30852-5}, pmid = {34265258}, issn = {1474-4457}, mesh = {Central Nervous System Viral Diseases ; Disease Outbreaks ; Enterovirus/*pathogenicity ; Enterovirus Infections/complications/*epidemiology ; *Epidemiological Monitoring ; Feces/virology ; Humans ; Myelitis ; Neuromuscular Diseases ; Paralysis/virology ; Poliomyelitis/*epidemiology ; Poliovirus/pathogenicity ; *Research ; }, abstract = {Poliovirus is known to most people in the world as the cause of polio, a devastating paralytic disease from the past. Success in polio eradication has understandably translated into stricter containment plans for poliovirus, coordinated by WHO. In this Personal View, we discuss the impact of recent biosafety level 3+ guidelines for handling potential poliovirus-containing diagnostic specimens, which has resulted in closure of many national WHO poliovirus reference laboratories. This reduction in laboratory capacity has a knock-on effect of capability to detect and characterise non-polio enteroviruses in samples obtained from patients with neurological symptoms. The development is of concern given the widespread circulation of non-polio enteroviruses, their role as the most common cause of meningitis worldwide, and their involvement in other severe neurological conditions, such as acute flaccid myelitis and encephalitis. These disease presentations have increased substantially in the past decade, and have been associated with major outbreaks of enterovirus D68 and enterovirus A71, leaving many who survived with lasting paralysis and disabilities. To address this growing gap in diagnostic and surveillance capability, we have established the European Non-Poliovirus Enterovirus Network (also known as ENPEN) as a supra-national, non-commercial, core reference consortium. Our consortium will develop, test, and implement generic surveillance platforms for non-polio enteroviruses and other emerging viral diseases.}, }
@article {pmid34264533, year = {2022}, author = {Zhang, X and Hu, Y and Ansari, AR and Akhtar, M and Chen, Y and Cheng, R and Cui, L and Nafady, AA and Elokil, AA and Abdel-Kafy, EM and Liu, H}, title = {Caecal microbiota could effectively increase chicken growth performance by regulating fat metabolism.}, journal = {Microbial biotechnology}, volume = {15}, number = {3}, pages = {844-861}, pmid = {34264533}, issn = {1751-7915}, mesh = {Animals ; Body Weight ; Cecum/microbiology ; *Chickens ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {It has been established that gut microbiota influences chicken growth performance and fat metabolism. However, whether gut microbiota affects chicken growth performance by regulating fat metabolism remains unclear. Therefore, seven-week-old chickens with high or low body weight were used in the present study. There were significant differences in body weight, breast and leg muscle indices, and cross-sectional area of muscle cells, suggesting different growth performance. The relative abundance of gut microbiota in the caecal contents at the genus level was compared by 16S rRNA gene sequencing. The results of LEfSe indicated that high body weight chickens contained Microbacterium and Sphingomonas more abundantly (P < 0.05). In contrast, low body weight chickens contained Slackia more abundantly (P < 0.05). The results of H &amp; E, qPCR, IHC, WB and blood analysis suggested significantly different fat metabolism level in serum, liver, abdominal adipose, breast and leg muscles between high and low body weight chickens. Spearman correlation analysis revealed that fat metabolism positively correlated with the relative abundance of Microbacterium and Sphingomonas while negatively correlated with the abundance of Slackia. Furthermore, faecal microbiota transplantation was performed, which verified that transferring faecal microbiota from adult chickens with high body weight into one-day-old chickens improved growth performance and fat metabolism in liver by remodelling the gut microbiota. Overall, these results suggested that gut microbiota could affect chicken growth performance by regulating fat metabolism.}, }
@article {pmid34263258, year = {2021}, author = {Shin, JH and Hays, RA and Warren, CA}, title = {Hospitalized Older Patients with Clostridioides difficile Infection Refractory to Conventional Antibiotic Therapy Benefit from Fecal Microbiota Transplant.}, journal = {Advances in geriatric medicine and research}, volume = {3}, number = {2}, pages = {}, pmid = {34263258}, support = {K08 AG064151/AG/NIA NIH HHS/United States ; R01 AI145322/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Options for Clostridioides difficile infection (CDI) refractory to conventional therapy are limited. Fecal microbiota transplant (FMT) is considered safe and effective treatment for recurrent CDI and could be a treatment option for refractory CDI. We investigated the efficacy and safety of FMT in hospitalized patients who were not responding to standard treatments for CDI.<br><br>METHODS: Electronic medical records of patients who received FMT inpatient for refractory CDI were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting.<br><br>RESULTS: Between July 2014 and December 2019, 9 patients (age 60-96) received FMT for CDI as inpatient for refractory or fulminant CDI. Most (7 of 9) of these patients had pseudomembranous colitis and underwent multiple FMTs (mean 2.15, range 1 to 3). Five patients had complete resolution and one patient had diarrhea that was C. difficile-negative. There was one recurrent CDI and two deaths, one of which may have been related to FMT or CDI. Compared to recurrent CDI at diagnosis, patients with refractory CDI had higher WBC and neutrophil counts, which decreased after FMT. The overall cure rate of FMT in refractory cases was 66.7%.<br><br>CONCLUSIONS: This study shows moderate efficacy of FMT for treatment of refractory CDI although multiple FMT treatment may need to be administered in the presence of pseudomembranous colitis. Inpatient FMT may be an alternative strategy for managing refractory CDI in this population of patients who may not have any effective medical treatment available.}, }
@article {pmid34262484, year = {2021}, author = {Song, W and Sun, LY and Zhu, ZJ and Wei, L and Qu, W and Zeng, ZG and Yang, YS}, title = {Characteristics of Gut Microbiota in Children With Biliary Atresia After Liver Transplantation.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {704313}, pmid = {34262484}, issn = {1664-042X}, abstract = {BACKGROUND AND AIMS: Biliary atresia (BA) is an idiopathic neonatal cholestasis and is the most common indication in pediatric liver transplantation (LT). Previous studies have suggested that the gut microbiota (GM) in BA is disordered. However, the effect of LT on gut dysbiosis in patients with BA has not yet been elucidated.<br><br>METHODS: Patients with BA (n = 16) and healthy controls (n = 10) were recruited. In the early life of children with BA, Kasai surgery is a typical procedure for restoring bile flow. According to whether BA patients had previously undergone Kasai surgery, we divided the post-LT patients into the with-Kasai group (n = 8) and non-Kasai group (n = 8). Fecal samples were collected in both the BA and the control group; among BA patients, samples were obtained again 6 months after LT. A total of 40 fecal samples were collected, of which 16 were pre-LT, 14 were post-LT (8 were with-Kasai, 6 were non-Kasai), and 10 were from the control group. Metagenomic sequencing was performed to evaluate the GM.<br><br>RESULTS: The Kruskal-Wallis test showed a statistically significant difference in the number of genes between the pre-LT and the control group, the pre-LT and the post-LT group (P < 0.05), but no statistical difference between the post-LT and the control group. Principal coordinate analysis also showed that the microbiome structure was similar between the post-LT and control group (P > 0.05). Analysis of the GM composition showed a significant decrease in Serratia, Enterobacter, Morganella, Skunalikevirus, and Phifllikevirus while short chain fatty acid (SCFA)-producing bacteria such as Roseburia, Blautia, Clostridium, Akkermansia, and Ruminococcus were increased after LT (linear discriminant analysis > 2, P < 0.05). However, they still did not reach the normal control level. Concerning functional profiles, lipopolysaccharide metabolism, multidrug resistance, polyamine biosynthesis, GABA biosynthesis, and EHEC/EPEC pathogenicity signature were more enriched in the post-LT group compared with the control group. Prior Kasai surgery had a specific influence on the postoperative GM.<br><br>CONCLUSION: LT partly improved the GM in patients with BA, which provided new insight into understanding the role of LT in BA.}, }
@article {pmid34262150, year = {2021}, author = {Lee, KA and Luong, MK and Shaw, H and Nathan, P and Bataille, V and Spector, TD}, title = {The gut microbiome: what the oncologist ought to know.}, journal = {British journal of cancer}, volume = {125}, number = {9}, pages = {1197-1209}, pmid = {34262150}, issn = {1532-1827}, support = {MR/N01183X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Bacteria/*classification/genetics/immunology ; Diet Therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Neoplasms/immunology/*microbiology/therapy ; Precision Medicine ; Probiotics ; Tumor Microenvironment ; }, abstract = {The gut microbiome (GM) has been implicated in a vast number of human pathologies and has become a focus of oncology research over the past 5 years. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation and protection against pathogens. Strong evidence is emerging to support the effects of the GM on the development of some malignancies but also on responses to cancer therapies, most notably, immune checkpoint inhibition. Tools for manipulating the GM including dietary modification, probiotics and faecal microbiota transfer (FMT) are in development. Current understandings of the many complex interrelationships between the GM, cancer, the immune system, nutrition and medication are ultimately based on a combination of short-term clinical trials and observational studies, paired with an ever-evolving understanding of cancer biology. The next generation of personalised cancer therapies focusses on molecular and phenotypic heterogeneity, tumour evolution and immune status; it is distinctly possible that the GM will become an increasingly central focus amongst them. The aim of this review is to provide clinicians with an overview of microbiome science and our current understanding of the role the GM plays in cancer.}, }
@article {pmid34261526, year = {2021}, author = {Cooke, NCA and Bala, A and Allard, JP and Hota, S and Poutanen, S and Taylor, VH}, title = {The safety and efficacy of fecal microbiota transplantation in a population with bipolar disorder during depressive episodes: study protocol for a pilot randomized controlled trial.}, journal = {Pilot and feasibility studies}, volume = {7}, number = {1}, pages = {142}, pmid = {34261526}, issn = {2055-5784}, support = {15T-009//Stanley Medical Research Institute/ ; }, abstract = {BACKGROUND: Bipolar disorder (BD) is a chronic, debilitating illness with significant medical morbidity, often secondary to current treatments, and a high recurrence rate. This burden of disease reflects limitations in the tolerability and efficacy of current treatments. There is a compelling body of evidence linking the gut microbiota to mental illness, and while microbial manipulation via probiotic use has been studied as a therapeutic in BD, targeted trials of fecal microbiota transplantation (FMT) have not been conducted in this population.<br><br>METHODS AND DESIGN: We describe a pilot randomized controlled trial of FMT in participants with BD depression to assess the feasibility, efficacy, safety, and tolerability of this intervention. Individuals between 18 and 65 years of age will be enrolled in the study if they meet diagnostic criteria for a major depressive episode of at least moderate severity in the context of a BD diagnosis and have not responded to treatment for BD. Participants will be randomized 1:1 to receive either screened and processed donor stool (allogenic FMT) or their own stool (autologous FMT) via colonoscopy and monitored for 24 weeks post intervention. Depressive and manic symptoms, treatment acceptability, and gastrointestinal and other side effects are assessed at baseline (prior to randomization) and weekly. Stool samples to assess microbiome composition are obtained at baseline and 3 and 6 months.<br><br>DISCUSSION: Currently, FMT represents a novel therapeutic option for treating BD depression. This protocol allows for the assessment of the feasibility, efficacy, acceptability, and safety of an intervention aimed at changing the microbiome in those with BD. Results from this pilot study will guide the development of larger trials of FMT for BD depression and may give more insight into how the gut microbiome are altered in those with BD depression.<br><br>TRIAL REGISTRATION: Clinical Trials Gov NCT03279224.}, }
@article {pmid34261379, year = {2021}, author = {Baunwall, SMD and Dahlerup, JF and Engberg, JH and Erikstrup, C and Helms, M and Juel, MA and Kjeldsen, J and Nielsen, HL and Nilsson, AC and Rode, AA and Vinter-Jensen, L and Hvas, CL}, title = {Danish national guideline for the treatment of Clostridioides difficile infection and use of faecal microbiota transplantation (FMT).}, journal = {Scandinavian journal of gastroenterology}, volume = {56}, number = {9}, pages = {1056-1077}, doi = {10.1080/00365521.2021.1922749}, pmid = {34261379}, issn = {1502-7708}, mesh = {Adult ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Denmark ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {Aim: This Danish national guideline describes the treatment of adult patients with Clostridioides (formerly Clostridium) difficile (CD) infection and the use of faecal microbiota transplantation (FMT). It suggests minimum standard for implementing an FMT service.Method: Four scientific societies appointed members for a working group which conducted a systematic literature review and agreed on the text and recommendations. All clinical recommendations were evalluated for evidence level and grade of recommendation.Results: In CD infection, the use of marketed and experimental antibiotics as well as microbiota-based therapies including FMT are described. An algorithm for evaluating treatment effect is suggested. The organisation of FMT, donor recruitment and screening, laboratory preparation, clinical application and follow-up are described.Conclusion: Updated evidence for the treatment of CD infection and the use of FMT is provided.}, }
@article {pmid34261137, year = {2021}, author = {Gu, X and Lu, Q and Zhang, C and Tang, Z and Chu, L}, title = {Clinical Application and Progress of Fecal Microbiota Transplantation in Liver Diseases: A Review.}, journal = {Seminars in liver disease}, volume = {41}, number = {4}, pages = {495-506}, pmid = {34261137}, issn = {1098-8971}, support = {National Natural Science Foundation of China//81904129/ ; College Student Innovation Funds Project for the Hebei University of Chinese Medicine//31800952/ ; College Student Innovation Funds Project for the Hebei University of Chinese Medicine//202014432203/ ; Fundamental Research Funds for the Southeast University//3218006405/ ; Fundamental Research Funds for the Southeast University//2242019s10024/ ; }, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis ; *Microbiota ; }, abstract = {The human gut harbors a dense and highly diverse microbiota of approximately 1,000 bacterial species. The interaction between the host and gut bacteria strongly influences human health. Numerous evidence suggest that intestinal flora imbalance is closely associated with the development and treatment of liver diseases, including acute liver injury and chronic liver diseases (cirrhosis, autoimmune liver disease, and fatty liver). Therefore, regulating the gut microbiota is expected to be a new method for the adjuvant treatment of liver diseases. Fecal microbiota transplantation (FMT) is defined as the transplantation of gut microbiota from healthy donors to sick patients via the upper or lower gastrointestinal route to restore the normal intestinal balance. In this study, we briefly review the current research on the gut microbiota and its link to liver diseases and then summarize the evidence to elucidate the clinical application and development of FMT in liver disease treatment.}, }
@article {pmid34258417, year = {2021}, author = {Zhou, H and Sun, J and Yu, B and Liu, Z and Chen, H and He, J and Mao, X and Zheng, P and Yu, J and Luo, J and Luo, Y and Yan, H and Ge, L and Chen, D}, title = {Gut microbiota absence and transplantation affect growth and intestinal functions: An investigation in a germ-free pig model.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {7}, number = {2}, pages = {295-304}, pmid = {34258417}, issn = {2405-6383}, abstract = {This study was conducted to investigate host-microbiota interactions and explore the effects of maternal gut microbiota transplantation on the growth and intestinal functions of newborns in a germ-free (GF) pig model. Twelve hysterectomy-derived GF Bama piglets were reared in 6 sterile isolators. Among them, 6 were considered as the GF group, and the other 6 were orally inoculated with healthy sow fecal suspension as fecal microbiota transplanted (FMT) group. Another 6 piglets from natural birth were regarded as the conventional (CV) group. The GF and FMT groups were hand-fed with Co60-γ-irradiated sterile milk powder, while the CV group was reared by lactating Bama sows. All groups were fed for 21 days. Then, all piglets and then were switched to sterile feed for another 21 days. Results showed that the growth performance, nutrient digestibility, and concentrations of short-chain fatty acids in the GF group decreased (P < 0.05). Meanwhile, the serum urea nitrogen concentration and digesta pH values in the GF group increased compared with those in the FMT and CV groups (P < 0.05). Compared with the CV group, the GF group demonstrated upregulation in the mRNA expression levels of intestinal barrier function-related genes in the small intestine (P < 0.05). In addition, the mRNA abundances of intestinal development and absorption-related genes in the small intestine and colon were higher in the GF group than in the CV and FMT groups (P < 0.05). The FMT group exhibited greater growth performance, lipase activity, and nutrient digestibility (P < 0.05), higher mRNA expression levels of intestinal development and barrier-related genes in the small intestine (P < 0.05), and lower mRNA abundances of pro-inflammatory factor in the colon and jejunum (P < 0.05) than the CV group. In conclusion, the absence of gut microbes impaired the growth and nutrient digestibility, and healthy sow gut microbiota transplantation increased the growth and nutrient digestibility and improved the intestinal development and barrier function of newborn piglets, indicating the importance of intestinal microbes for intestinal development and functions.}, }
@article {pmid34258416, year = {2021}, author = {Peng, J and Tang, Y and Huang, Y}, title = {Gut health: The results of microbial and mucosal immune interactions in pigs.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {7}, number = {2}, pages = {282-294}, pmid = {34258416}, issn = {2405-6383}, abstract = {There are a large number of microorganisms in the porcine intestinal tract. These microorganisms and their metabolites contribute to intestinal mucosal immunity, which is of great importance to the health of the host. The host immune system can regulate the distribution and composition of intestinal microorganisms and regulate the homeostasis of intestinal flora by secreting a variety of immune effector factors, such as mucin, secretory immunoglobulin A (sIgA), regenerating islet-derived III (RegIII)γ, and defensin. Conversely, intestinal microorganisms can also promote the differentiation of immune cells including regulatory T cells (Treg) and Th17 cells through their specific components or metabolites. Studies have shown that imbalances in the intestinal flora can lead to bacterial translocation and compromised intestinal barrier function, affecting the health of the body. This review focuses on the composition of the pig intestinal flora and the characteristics of intestinal mucosal immunity, discusses the interaction mechanism between the flora and intestinal mucosal immunity, as well as the regulation through fecal microbiota transplantation (FMT), dietary nutritional composition, probiotics and prebiotics of pig intestinal microecology. Finally, this review provides insights into the relationship between intestinal microorganisms and the mucosal immune system.}, }
@article {pmid34257825, year = {2021}, author = {Gao, T and Wang, Z and Cao, J and Dong, Y and Chen, Y}, title = {Melatonin Ameliorates Corticosterone-Mediated Oxidative Stress-Induced Colitis in Sleep-Deprived Mice Involving Gut Microbiota.}, journal = {Oxidative medicine and cellular longevity}, volume = {2021}, number = {}, pages = {9981480}, pmid = {34257825}, issn = {1942-0994}, mesh = {Animals ; Antioxidants/pharmacology/*therapeutic use ; Colitis/*chemically induced ; Corticosterone/*adverse effects ; Disease Models, Animal ; Gastrointestinal Microbiome/*drug effects ; Male ; Melatonin/pharmacology/*therapeutic use ; Mice ; Oxidative Stress ; Sleep Deprivation/*drug therapy ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a result of a complex interplay, making development of a specific treatment a challenging task. Corticosterone was considered a risk factor of stress relative enteritis. Our previous studies found that melatonin exerts an improvement effect in sleep deprivation (SD)- induced corticosterone overproduction and colitis. A present study further explored the mechanism whereby melatonin prevented corticosterone-mediated SD-induced colitis.<br><br>METHODS: A 72-hour SD mouse model with or without melatonin supplementation and fecal microbiota transplantation (FMT) to investigate the core role of corticosterone in melatonin-mediated gut microbiota improving SD-induced colitis. Further, corticosterone-treated mice were assessed to the effect of melatonin on corticosterone-mediated gut microbiota dysbiosis-induced colitis. Meanwhile, an in vitro test studied modulatory mechanism of metabolite melatonin.<br><br>RESULTS: SD caused an excessive corticosterone, gut microbiota disorder and colitis phenotype. Similarly, corticosterone-supplemented mice also exhibited gut microbiota dysbiosis and colitis, and the FMT from SD-mice to normal mice could restore the SD-like colitis, but no change in the corticosterone level, which suggested that corticosterone-mediated intestinal microbiota imbalance plays a central role in SD-induced colitis. Further, we demonstrated melatonin-mediated MT2 weakened GR feedback, suppressed oxidative stress, restored the intestinal microbiota and its metabolites homeostasis, and inactivated the STAT3/AP-1/NF-&#x3ba;B pathway-induced inflammatory response in vivo and in vitro.<br><br>CONCLUSIONS: We revealed that excessive corticosterone is a core risk factor for SD-induced colitis and provided a better understanding of the effects of melatonin, expected to be a personalized targeted therapy drug, on corticosterone-mediated gut microbiota inducing colitis.}, }
@article {pmid34252410, year = {2022}, author = {Ianiro, G and Gasbarrini, A and Cammarota, G}, title = {Evaluating Donor Microbiome Before Fecal Microbiota Transplantation.}, journal = {Gastroenterology}, volume = {162}, number = {3}, pages = {993-994}, doi = {10.1053/j.gastro.2021.07.003}, pmid = {34252410}, issn = {1528-0012}, mesh = {Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Tissue Donors ; }, }
@article {pmid34252073, year = {2021}, author = {Verma, S and Dutta, SK and Firnberg, E and Phillips, L and Vinayek, R and Nair, PP}, title = {Identification and engraftment of new bacterial strains by shotgun metagenomic sequence analysis in patients with recurrent Clostridioides difficile infection before and after fecal microbiota transplantation and in healthy human subjects.}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0251590}, pmid = {34252073}, issn = {1932-6203}, mesh = {Humans ; *Fecal Microbiota Transplantation ; Female ; Male ; *Clostridium Infections/therapy/microbiology ; Middle Aged ; *Metagenomics/methods ; Aged ; Adult ; Feces/microbiology ; Gastrointestinal Microbiome ; Clostridioides difficile/genetics/isolation &amp; purification ; Recurrence ; Bacteria/genetics/classification/isolation &amp; purification ; Dysbiosis/microbiology/therapy ; Metagenome ; }, abstract = {BACKGROUND: Recurrent Clostridioides diffícile infection (RCDI) is associated with major bacterial dysbiosis and colitis. Fecal microbiota transplantation (FMT) is a highly effective therapeutic modality for RCDI. While several studies have identified bacterial species associated with resolution of symptoms in patients, characterization of the fecal microbiome at the bacterial strain level in RCDI patients before and after FMT and healthy donors, has been lacking. The aim of this study was to examine the ability of bacterial strains from healthy donors to engraft in the gastrointestinal tract of patients with RCDI following FMT.<br><br>METHODS: Fecal samples were collected from 22 patients with RCDI before and after FMT and their corresponding healthy donors. Total DNA was extracted from each sample and analyzed by shotgun metagenomic sequencing. The Cosmos-ID analysis platform was used for taxonomic assignment of sequences and calculation of the relative abundance (RA) of bacterial species and strains. From these data, the total number of bacterial strains (BSI), Shannon diversity index, dysbiosis index (DI), and bacterial engraftment factor, were calculated for each strain.<br><br>FINDINGS: A marked reduction (p<0&#xb7;0001) in the RA of total and specific bacterial strains, especially from phylum Firmicutes, was observed in RCDI patients prior to FMT. This change was associated with an increase in the DI (p<0&#xb7;0001) and in pathobiont bacterial strains from phylum Proteobacteria, such as Escherichia coli O157:H7 and Klebsiella pneumoniae UCI 34. BSI was significantly lower in this group of patients as compared to healthy donors and correlated with the Shannon Index. (p<0&#xb7;0001). Identification and engraftment of bacterial strains from healthy donors revealed a greater diversity and higher relative abundance of short-chain fatty acid (SCFA)-producing bacterial strains, including Lachnospiraceae bacterium 5_1_63FAA_u_t, Dorea formicigenerans ATCC 27755, Anaerostipes hadrusand others, in RCDI patients after FMT.<br><br>INTERPRETATION: These observations identify a group of SCFA-producing bacterial strains from healthy donors that engraft well in patients with RCDI following FMT and are associated with complete resolution of clinical symptoms and bacterial dysbiosis.}, }
@article {pmid34250000, year = {2021}, author = {Tokuhara, D}, title = {Role of the Gut Microbiota in Regulating Non-alcoholic Fatty Liver Disease in Children and Adolescents.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {700058}, pmid = {34250000}, issn = {2296-861X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in children and adolescents. Although obesity is the leading cause of NAFLD, the etiologies of NAFLD are multifactorial (e.g., high-fat diet, a lack of exercise, gender, maternal obesity, the antibiotic use), and each of these factors leads to dysbiosis of the gut microbiota community. The gut microbiota is a key player in the development and regulation of the gut mucosal immune system as well as the regulation of both NAFLD and obesity. Dysbiosis of the gut microbiota promotes the development of NAFLD via alteration of gut-liver homeostasis, including disruption of the gut barrier, portal transport of bacterial endotoxin (lipopolysaccharide) to the liver, altered bile acid profiles, and decreased concentrations of short-chain fatty acids. In terms of prevention and treatment, conventional approaches (e.g., dietary and exercise interventions) against obesity and NAFLD have been confirmed to recover the dysbiosis and dysbiosis-mediated altered metabolism. In addition, increased understanding of the importance of gut microbiota-mediated homeostasis in the prevention of NAFLD suggests the potential effectiveness of gut microbiota-targeted preventive and therapeutic strategies (e.g., probiotics and fecal transplantation) against NAFLD in children and adolescents. This review comprehensively summarizes our current knowledge of the gut microbiota, focusing on its interaction with NAFLD and its potential therapeutic role in obese children and adolescents with this disorder.}, }
@article {pmid34249452, year = {2021}, author = {Matsukawa, H and Iida, N and Kitamura, K and Terashima, T and Seishima, J and Makino, I and Kannon, T and Hosomichi, K and Yamashita, T and Sakai, Y and Honda, M and Yamashita, T and Mizukoshi, E and Kaneko, S}, title = {Dysbiotic gut microbiota in pancreatic cancer patients form correlation networks with the oral microbiota and prognostic factors.}, journal = {American journal of cancer research}, volume = {11}, number = {6}, pages = {3163-3175}, pmid = {34249452}, issn = {2156-6976}, abstract = {Microbiota in the gut and oral cavities of pancreatic cancer (PC) patients differ from those of healthy persons, and bacteria in PC tissues are associated with patients' prognoses. However, the species-level relationship between a dysbiotic gut, oral and cancerous microbiota, and prognostic factors remains unknown. Whole-genome sequencing was performed with fecal DNA from 24 PC patients and 18 healthy persons (HD). Microbial taxonomies, metabolic pathways, and viral presence were determined. DNA was sequenced from saliva and PC tissues, and the association between the gut, oral, and cancer microbiota and prognostic factors in PC patients was analyzed. The PC microbiota were altered from those of the healthy microbiota in terms of microbial taxonomy, pathways and viral presence. Twenty-six species differed significantly between the PC and HD microbiota. Six fecal microbes, including Klebsiella pneumoniae, were associated with an increased hazard of death. In the co-occurrence network, microbes that were abundant in PC patients were plotted close together and formed clusters with prognosis-associated microbes, including K. pneumoniae. Multiple salivary microbes were present in the co-occurrence network. Microbacterium and Stenotrophomonas were detected in the PC tissues and formed a network with the fecal and salivary microbes. The dysbiotic gut microbiota in the PC patients formed a complex network with the oral and cancerous microbiota, and gut microbes abundant in the PC patients were closely linked with poor prognostic factors in the network.}, }
@article {pmid34246956, year = {2021}, author = {Deng, L and Shi, Y and Liu, P and Wu, S and Lv, Y and Xu, H and Chen, X}, title = {GeGen QinLian decoction alleviate influenza virus infectious pneumonia through intestinal flora.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {141}, number = {}, pages = {111896}, doi = {10.1016/j.biopha.2021.111896}, pmid = {34246956}, issn = {1950-6007}, mesh = {Animals ; CD4-Positive T-Lymphocytes/drug effects ; Cytokines/metabolism ; Drugs, Chinese Herbal/*therapeutic use ; Female ; Gastrointestinal Microbiome/*drug effects ; Lymph Nodes/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; NF-kappa B/drug effects ; *Orthomyxoviridae ; Pneumonia/etiology/pathology/prevention &amp; control ; Pneumonia, Viral/*drug therapy/mortality ; Receptor-Interacting Protein Serine-Threonine Kinase 2/drug effects ; Signal Transduction/drug effects ; }, abstract = {Influenza in humans is often accompanied by gastroenteritis-like symptoms. GeGen QinLian decoction (GQD), a Chinese herb formula, has been widely used to treat infectious diarrhea for centuries and has the effect of restoring intestinal flora. Studies have also reported that GQD were used to treat patients with influenza. However, whether regulating the intestinal flora is one of the ways GQD treats influenza has not been confirmed. In present research, we conducted a systemic pharmacological study, and the results showed that GQD may acts through multiple targets and pathways. In influenza-infected mice, GQD treatment reduced mortality and lung inflammation. Most importantly, the mortality and lung inflammation were also reduced in influenza-infected mice that have undergone fecal microbiota transplantation (FMT) from GQD (FMT-GQD) treated mice. GQD treatment or FMT-GQD treatment restores the intestinal flora, resulting in an increase in Akkermansia_muciniphila, Desulfovibrio_C21_c20 and Lactobacillus_salivarius, and a decrease in Escherichia_coli. FMT-GQD treatment inhibited the NOD/RIP2/NF-κB signaling pathway in the intestine and affected the expression of downstream related inflammatory cytokines in mesenteric lymph nodes (mLNs) and serum. In addition, FMT-GQD treatment showed systemic protection by restraining the inflammatory differentiation of CD4[+] T cells. In conclusion, our study shows that GQD can affect systemic immunity, at least in part, through the intestinal flora, thereby protect the mice against influenza virus infectious pneumonia.}, }
@article {pmid34246792, year = {2021}, author = {Ono, S and Takeshita, K and Kiridoshi, Y and Kato, M and Kamiya, T and Hoshino, A and Yanagimachi, M and Arai, K and Takeuchi, I and Toita, N and Imamura, T and Sasahara, Y and Sugita, J and Hamamoto, K and Takeuchi, M and Saito, S and Onuma, M and Tsujimoto, H and Yasui, M and Taga, T and Arakawa, Y and Mitani, Y and Yamamoto, N and Imai, K and Suda, W and Hattori, M and Ohara, O and Morio, T and Honda, K and Kanegane, H}, title = {Hematopoietic Cell Transplantation Rescues Inflammatory Bowel Disease and Dysbiosis of Gut Microbiota in XIAP Deficiency.}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {9}, number = {10}, pages = {3767-3780}, doi = {10.1016/j.jaip.2021.05.045}, pmid = {34246792}, issn = {2213-2201}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Genetic Diseases, X-Linked ; *Hematopoietic Stem Cell Transplantation ; Humans ; *Inflammatory Bowel Diseases/therapy ; Lymphoproliferative Disorders ; X-Linked Inhibitor of Apoptosis Protein/genetics ; }, abstract = {BACKGROUND: X-linked inhibitor of apoptosis protein (XIAP) deficiency is an infrequent inborn error of immunity that is often associated with refractory inflammatory bowel disease (IBD). The natural course of XIAP deficiency is typically associated with poor prognosis, and hematopoietic cell transplantation (HCT) is the only curative treatment.<br><br>OBJECTIVE: To study (1) the effect of HCT on patients with XIAP deficiency undergoing HCT, (2) the status of XIAP deficiency-associated IBD after HCT, and (3) the gut microbiota of XIAP deficiency-associated IBD before and after HCT.<br><br>METHODS: A nationwide survey of patients with XIAP deficiency was conducted. A spreadsheet questionnaire was collected from the physicians. Feces samples collected from the patients before and after HCT and their healthy family members were analyzed.<br><br>RESULTS: Twenty-six patients with XIAP deficiency underwent HCT by the end of March 2020, and 22 patients (84.6%) survived. All the survivors underwent a fludarabine-based reduced-intensity condition regimen. Acute graft-versus-host disease was observed in 17 patients (65.4%). Nineteen patients experienced refractory IBD before undergoing HCT. IBD improved remarkably after HCT. After HCT, the colonoscopic and pathological symptoms were restored to normal, and the pediatric ulcerative colitis activity index improved significantly. Gut microbiota indicated dysbiosis before HCT; however, it was improved to resemble that of the healthy family members after&#xa0;HCT.<br><br>CONCLUSIONS: This study revealed that HCT has a favorable outcome for XIAP deficiency. HCT rescues gut inflammation and dysbiosis in patients with XIAP deficiency.}, }
@article {pmid34245901, year = {2021}, author = {Reigadas, E and van Prehn, J and Falcone, M and Fitzpatrick, F and Vehreschild, MJGT and Kuijper, EJ and Bouza, E and , }, title = {How to: prophylactic interventions for prevention of Clostridioides difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {27}, number = {12}, pages = {1777-1783}, doi = {10.1016/j.cmi.2021.06.037}, pmid = {34245901}, issn = {1469-0691}, mesh = {*Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; *Clostridium Infections/prevention &amp; control/therapy ; *Fecal Microbiota Transplantation ; Humans ; Recurrence ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhoea, despite existing guidelines for infection control measures and antimicrobial stewardship. The high associated health and economic burden of CDI calls for novel strategies to prevent the development and spread of CDI in susceptible patients.<br><br>OBJECTIVES: We aim to review CDI prophylactic treatment strategies and their implementation in clinical practice.<br><br>SOURCES: We searched PubMed, Embase, Emcare, Web of Science, and the COCHRANE Library databases to identify prophylactic interventions aimed at prevention of CDI. The search was restricted to articles published in English since 2012.<br><br>CONTENT: A toxin-based vaccine candidate is currently being investigated in a phase III clinical trial. However, a recent attempt to develop a toxin-based vaccine has failed. Conventional probiotics have not yet proved to be an effective strategy for prevention of CDI. New promising microbiota-based interventions that bind and inactivate concomitantly administered antibiotics, such as ribaxamase and DAV-132, have been developed. Prophylaxis of CDI with C.&#xa0;difficile antibiotics should not be performed routinely and should be considered only for secondary prophylaxis in very selected patients who are at the highest imminent risk for recurrent CDI (R-CDI) after a thorough evaluation. Faecal microbiota transplantation (FMT) has proved to be a very effective treatment for patients with multiple recurrences. Bezlotoxumab provides protection against R-CDI, mainly in patients with primary episodes and a high risk of relapse.<br><br>IMPLICATIONS: There are no proven effective, evidenced-based prophylaxis options for primary CDI. As for secondary prevention, FMT is considered the option of choice in patients with multiple recurrences. Bezlotoxumab can be added to standard treatment for patients at high risk for R-CDI. The most promising strategies are those aimed at reducing changes in intestinal microbiota and development of a new effective non-toxin-based vaccine.}, }
@article {pmid34239510, year = {2021}, author = {Young, RB and Marcelino, VR and Chonwerawong, M and Gulliver, EL and Forster, SC}, title = {Key Technologies for Progressing Discovery of Microbiome-Based Medicines.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {685935}, pmid = {34239510}, issn = {1664-302X}, abstract = {A growing number of experimental and computational approaches are illuminating the "microbial dark matter" and uncovering the integral role of commensal microbes in human health. Through this work, it is now clear that the human microbiome presents great potential as a therapeutic target for a plethora of diseases, including inflammatory bowel disease, diabetes and obesity. The development of more efficacious and targeted treatments relies on identification of causal links between the microbiome and disease; with future progress dependent on effective links between state-of-the-art sequencing approaches, computational analyses and experimental assays. We argue determining causation is essential, which can be attained by generating hypotheses using multi-omic functional analyses and validating these hypotheses in complex, biologically relevant experimental models. In this review we discuss existing analysis and validation methods, and propose best-practice approaches required to enable the next phase of microbiome research.}, }
@article {pmid34238831, year = {2021}, author = {Hourigan, SK and Nicholson, MR and Kahn, SA and Kellermayer, R}, title = {Updates and Challenges in Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {73}, number = {4}, pages = {430-432}, pmid = {34238831}, issn = {1536-4801}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; K23 HD099240/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; *COVID-19 ; Child ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; SARS-CoV-2 ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is currently the most effective but loosely regulated therapy, for recurrent Clostridioides difficile infection (rCDI) in pediatrics. Over the last 2 years, there have been mounting challenges in the ability to provide FMT to pediatric patients. Firstly, an Food and Drug Administration (FDA) safety alert in 2019 reported transmission of a multidrug resistant organism from FMT donor to recipient resulting in the death of 1 patient. Secondly, the coronavirus disease 2019 (COVID-19) pandemic induced further safety and regulatory challenges. Biotherapeutics are promising and more readily regulated treatment options for rCDI, which may replace FMT in the near future for adults upon regulatory agency approvals. Such approvals, however, are expected to be significantly delayed for children, raising concerns for limited access to effective treatment for children with rCDI. In this commentary, we discuss the recent challenges and future directions of FMT and microbial therapeutics in children with rCDI.}, }
@article {pmid34238386, year = {2021}, author = {Bermudez-Martin, P and Becker, JAJ and Caramello, N and Fernandez, SP and Costa-Campos, R and Canaguier, J and Barbosa, S and Martinez-Gili, L and Myridakis, A and Dumas, ME and Bruneau, A and Cherbuy, C and Langella, P and Callebert, J and Launay, JM and Chabry, J and Barik, J and Le Merrer, J and Glaichenhaus, N and Davidovic, L}, title = {The microbial metabolite p-Cresol induces autistic-like behaviors in mice by remodeling the gut microbiota.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {157}, pmid = {34238386}, issn = {2049-2618}, support = {MR/M501797/1/MRC_/Medical Research Council/United Kingdom ; MR/M50197/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Autism Spectrum Disorder ; *Autistic Disorder/etiology ; Cresols ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {BACKGROUND: Autism spectrum disorders (ASD) are associated with dysregulation of the microbiota-gut-brain axis, changes in microbiota composition as well as in the fecal, serum, and urine levels of microbial metabolites. Yet a causal relationship between dysregulation of the microbiota-gut-brain axis and ASD remains to be demonstrated. Here, we hypothesized that the microbial metabolite p-Cresol, which is more abundant in ASD patients compared to neurotypical individuals, could induce ASD-like behavior in mice.<br><br>RESULTS: Mice exposed to p-Cresol for 4 weeks in drinking water presented social behavior deficits, stereotypies, and perseverative behaviors, but no changes in anxiety, locomotion, or cognition. Abnormal social behavior induced by p-Cresol was associated with decreased activity of central dopamine neurons involved in the social reward circuit. Further, p-Cresol induced changes in microbiota composition and social behavior deficits could be transferred from p-Cresol-treated mice to control mice by fecal microbiota transplantation (FMT). We also showed that mice transplanted with the microbiota of p-Cresol-treated mice exhibited increased fecal p-Cresol excretion,&#xa0;compared to mice transplanted with the microbiota of control mice. In addition, we identified possible p-Cresol bacterial producers. Lastly, the microbiota of control mice rescued social interactions, dopamine neurons excitability, and fecal p-Cresol levels when transplanted to p-Cresol-treated mice.<br><br>CONCLUSIONS: The microbial metabolite p-Cresol induces selectively ASD core behavioral symptoms in mice. Social behavior deficits induced by p-Cresol are dependant on changes in microbiota composition. Our study paves the way for therapeutic interventions targeting the microbiota and p-Cresol production&#xa0;to treat patients with ASD. Video abstract.}, }
@article {pmid34238227, year = {2021}, author = {Crothers, JW and Chu, ND and Nguyen, LTT and Phillips, M and Collins, C and Fortner, K and Del Rio-Guerra, R and Lavoie, B and Callas, P and Velez, M and Cohn, A and Elliott, RJ and Wong, WF and Vo, E and Wilcox, R and Smith, M and Kassam, Z and Budd, R and Alm, EJ and Mawe, GM and Moses, PL}, title = {Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {281}, pmid = {34238227}, issn = {1471-230X}, support = {P20 GM125498/GM/NIGMS NIH HHS/United States ; R01 DK113800/DK/NIDDK NIH HHS/United States ; P30GM118228/NH/NIH HHS/United States ; DK113800/NH/NIH HHS/United States ; }, mesh = {*Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Pilot Projects ; Prospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT).<br><br>METHODS: Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12&#xa0;weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36&#xa0;weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint.<br><br>RESULTS: Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI&#x2009;=&#x2009;0.38-infinity, p&#x2009;=&#x2009;0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response.<br><br>CONCLUSION: These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&amp;draw=2&amp;rank=1 .}, }
@article {pmid34237681, year = {2021}, author = {Segal, A and Zlotnik, Y and Moyal-Atias, K and Abuhasira, R and Ifergane, G}, title = {Fecal microbiota transplant as a potential treatment for Parkinson's disease - A case series.}, journal = {Clinical neurology and neurosurgery}, volume = {207}, number = {}, pages = {106791}, doi = {10.1016/j.clineuro.2021.106791}, pmid = {34237681}, issn = {1872-6968}, mesh = {Aged ; Constipation/etiology ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/complications/*therapy ; Treatment Outcome ; }, abstract = {OBJECTIVE: We aimed to determine whether fecal microbiota transplant (FMT) is safe and possibly efficacious in treating constipation, motor, and non-motor symptoms in Parkinson's disease (PD) patients.<br><br>METHODS: Patients with PD, constipation and an indication for screening colonoscopy were treated with FMT. The study was conducted from December 2017 to November 2019, and clinical outcomes assessing motor, non-motor and constipation symptoms were compared at baseline (week 0) and at 2, 4, 8, 12, 16, 20, and 24 weeks after the FMT.<br><br>RESULTS: Six patients (3 men, age range 47-73, median age 52) were treated with FMT. Four weeks following the FMT, motor, non-motor and constipation scores were improved in 5 of 6 patients. At week 24, compared to before the FMT, the changes in motor scores ranged from -&#xa0;13-7 points, in non-motor scores from -&#xa0;2 to -&#xa0;45 points, and in constipation scores from -&#xa0;12-1 point. One patient had a serious adverse event requiring admission for observation only, and no adverse events were observed in all other patients.<br><br>CONCLUSIONS: In this preliminary uncontrolled case series of 6 PD patients, a treatment with donor FMT infused via colonoscopy, was safe and resulted in improvement of PD motor and non-motor symptoms, including constipation, at 6 months. Further research is needed to assess longer-term maintenance of efficacy and safety, including in large scale randomized controlled trials.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov - NCT03876327.}, }
@article {pmid34236740, year = {2021}, author = {El-Salhy, M and Hausken, T and Hatlebakk, JG}, title = {Current status of fecal microbiota transplantation for irritable bowel syndrome.}, journal = {Neurogastroenterology and motility}, volume = {33}, number = {11}, pages = {e14157}, doi = {10.1111/nmo.14157}, pmid = {34236740}, issn = {1365-2982}, mesh = {*Fecal Microbiota Transplantation ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal functional disorder. Although IBS is a benign condition, it reduces the quality of life considerably. While there is currently no effective treatment for this disorder, fecal microbiota transplantation (FMT) seems to be promising.<br><br>PURPOSE: The aim of this review was to analysis possible factors affecting the success or failure of the randomized controlled trials (RCTs) of FMT for IBS and highlighting the gaps in our knowledge that need to be filled and of sketching a possible model for successful FMT in IBS patients.<br><br>METHODS: A systematic search was conducted of literature published in English from January 2015 to December 2020 using the keywords: fecal microbiota transplantation, randomized trials, and IBS.<br><br>KEY RESULTS: Seven randomized controlled trials (RCTs) on the efficacy of FMT for IBS were found in the literature. Four of the seven RCTs found various positive effects, while the other three did not find any effect.<br><br>CONCLUSIONS AND INFERENCES: The efficacy of FMT for IBS appears to be donor-dependent. The effective (super) donor would need to have a favorable microbiota signature, and 11 clinical criteria that are known to be associated with a favorable microbiota have been suggested for selecting FMT donors for IBS. Comparing the microbiota of the effective donors with those of healthy subjects would reveal the favorable microbiota signature required for a super-donor. However, the studies reviewed were not designed to compare efficacy of different donor types. The dose of the fecal transplant is also an important factor influencing the outcome of FMT for IBS. However, further studies designed to test the effect of fecal transplant dose are needed to answer this question. Administering the fecal transplant to either the small or large intestine seems to be effective, but the optimal route of administration remains to be determined. Moreover, whether single or repeated FMT is more effective is also still unclear. A 1-year follow-up of IBS patients who received FMT showed that adverse events of abdominal pain, diarrhea, and constipation were both mild and self-limiting.}, }
@article {pmid34236075, year = {2021}, author = {Stott, KJ and Phillips, B and Parry, L and May, S}, title = {Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer.}, journal = {Bioscience reports}, volume = {41}, number = {7}, pages = {}, pmid = {34236075}, issn = {1573-4935}, support = {27517/CRUK_/Cancer Research UK/United Kingdom ; A17196/CRUK_/Cancer Research UK/United Kingdom ; C23498/A27517/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Bacteria/*drug effects/growth &amp; development/metabolism/pathogenicity ; Colorectal Neoplasms/metabolism/microbiology/*therapy ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Humans ; Probiotics/adverse effects/*therapeutic use ; Treatment Outcome ; }, abstract = {Over the last few decades it has been established that the complex interaction between the host and the multitude of organisms that compose the intestinal microbiota plays an important role in human metabolic health and disease. Whilst there is no defined consensus on the composition of a healthy microbiome due to confounding factors such as ethnicity, geographical locations, age and sex, there are undoubtably populations of microbes that are consistently dysregulated in gut diseases including colorectal cancer (CRC). In this review, we discuss the most recent advances in the application of the gut microbiota, not just bacteria, and derived microbial compounds in the diagnosis of CRC and the potential to exploit microbes as novel agents in the management and treatment of CRC. We highlight examples of the microbiota, and their derivatives, that have the potential to become standalone diagnostic tools or be used in combination with current screening techniques to improve sensitivity and specificity for earlier CRC diagnoses and provide a perspective on their potential as biotherapeutics with translatability to clinical trials.}, }
@article {pmid34233682, year = {2021}, author = {Cunningham, AL and Stephens, JW and Harris, DA}, title = {A review on gut microbiota: a central factor in the pathophysiology of obesity.}, journal = {Lipids in health and disease}, volume = {20}, number = {1}, pages = {65}, pmid = {34233682}, issn = {1476-511X}, mesh = {Animals ; Gastrointestinal Microbiome/*physiology ; Homeostasis/physiology ; Humans ; Obesity/etiology/microbiology/*physiopathology ; }, abstract = {Obesity and its complications constitute a substantial burden. Considerable published research describes the novel relationships between obesity and gut microbiota communities. It is becoming evident that microbiota behave in a pivotal role in their ability to influence homeostatic mechanisms either to the benefit or detriment of host health, the extent of which is not fully understood. A greater understanding of the contribution of gut microbiota towards host pathophysiology is revealing new therapeutic avenues to tackle the global obesity epidemic. This review focuses on causal relationships and associations with obesity, proposed central mechanisms encouraging the development of obesity and promising prospective methods for microbiota manipulation.}, }
@article {pmid34232990, year = {2021}, author = {Li, Y and Honda, K}, title = {Toward the development of defined microbial therapeutics.}, journal = {International immunology}, volume = {33}, number = {12}, pages = {761-766}, doi = {10.1093/intimm/dxab038}, pmid = {34232990}, issn = {1460-2377}, mesh = {Animals ; Clostridium Infections/immunology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Humans ; Phenotype ; }, abstract = {The collection of micro-organisms living in the mammalian gastrointestinal tract, termed the gut microbiota, has been shown to have profound impacts on host health and increasingly is regarded as a viable therapeutic target. Clinical studies of fecal microbiota transplantation have demonstrated potential efficacy of microbiota-based therapies for diseases including Clostridioides difficile infections, inflammatory bowel disease, graft-versus-host disease and cancer. However, the lack of understanding of the active ingredients and potential risks of such therapies pose challenges for clinical application. Meanwhile, efforts are being made to identify effector microbes directly associated with a given phenotype, to establish causality and to devise well-characterized microbial therapeutics for clinical use. Strategies based on defined microbial components will likely enhance the potential of microbiota-targeted therapies.}, }
@article {pmid34232137, year = {2021}, author = {Kociolek, LK and Crews, JD and Schwenk, HT}, title = {Recent advances in Clostridioides difficile infection epidemiology, diagnosis and treatment in children.}, journal = {Current opinion in infectious diseases}, volume = {34}, number = {5}, pages = {527-532}, doi = {10.1097/QCO.0000000000000753}, pmid = {34232137}, issn = {1473-6527}, mesh = {Adult ; Child ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/drug therapy/epidemiology ; *Communicable Diseases ; Fecal Microbiota Transplantation ; Humans ; Randomized Controlled Trials as Topic ; }, abstract = {PURPOSE OF REVIEW: The US Centers for Disease Control and Prevention (CDC) classified Clostridioides difficile as an 'urgent' public health threat that requires 'urgent and aggressive action'. This call to action has led to new discoveries that have advanced C. difficile infection (CDI) epidemiology, diagnosis and treatment, albeit predominantly in adults. In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published clinical practice guidelines for both adults and children. At that time, recommendations in children were generally limited to relatively low-quality evidence.<br><br>RECENT FINDINGS: Since publication of this guidance, there have been many advancements in the understanding of CDI in children. These include better understanding of healthcare settings as uncommon sources of C. difficile acquisition in children; risk factors for recurrent and community-associated CDI; performance of diagnostic tests in children and strategies for optimizing their use; and a more rigorous evidence base for CDI treatment in children, including the first-ever randomized controlled trial of CDI treatment in children and the largest study of fecal microbiota transplantation in children.<br><br>SUMMARY: This review highlights the most recent salient advancements in paediatric CDI knowledge and practice that supplement published clinical guidance provided prior to these advancements.}, }
@article {pmid34230217, year = {2022}, author = {Biliński, J and Winter, K and Jasiński, M and Szczęś, A and Bilinska, N and Mullish, BH and Małecka-Panas, E and Basak, GW}, title = {Rapid resolution of COVID-19 after faecal microbiota transplantation.}, journal = {Gut}, volume = {71}, number = {1}, pages = {230-232}, doi = {10.1136/gutjnl-2021-325010}, pmid = {34230217}, issn = {1468-3288}, mesh = {Aged, 80 and over ; COVID-19/complications/diagnosis/*therapy ; Clostridium Infections/complications/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Male ; Young Adult ; }, }
@article {pmid34226737, year = {2021}, author = {Mocanu, V and Zhang, Z and Deehan, EC and Kao, DH and Hotte, N and Karmali, S and Birch, DW and Samarasinghe, KK and Walter, J and Madsen, KL}, title = {Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial.}, journal = {Nature medicine}, volume = {27}, number = {7}, pages = {1272-1279}, pmid = {34226737}, issn = {1546-170X}, support = {//CIHR/Canada ; }, mesh = {Dietary Fiber/*therapeutic use ; Dietary Supplements ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Female ; Fermentation/physiology ; Gastrointestinal Microbiome/physiology ; Humans ; Insulin Resistance/*physiology ; Male ; Metabolic Syndrome/*therapy ; Middle Aged ; Obesity, Morbid/*therapy ; Proof of Concept Study ; }, abstract = {Fecal microbial transplantation (FMT) from lean donors to patients with obesity has been associated with metabolic benefits, yet results so far have been inconsistent. In this study, we tested the application of daily fiber supplementation as an adjunct to FMT therapy to modulate cardiometabolic outcomes. We performed a double-blind randomized trial in patients with severe obesity and metabolic syndrome receiving oral FMT, to test high-fermentable (HF) and low-fermentable (LF) fiber supplements (NCT03477916). Seventy participants were randomized to the FMT-HF (n = 17), FMT-LF (n = 17), HF (n = 17) and LF (n = 19) groups. The primary outcome was the assessment of change in insulin sensitivity from baseline to 6 weeks using the homeostatic model assessment (HOMA2-IR/IS). After 6 weeks, only patients in the FMT-LF group had significant improvements in HOMA2-IR (3.16 ± 3.01 at 6 weeks versus 3.77 ± 3.57 at baseline; P = 0.02). No difference in HOMA2-IR was observed over this period for those in the FMT-HF group (3.25 ± 1.70 at 6 weeks versus 3.17 ± 1.72 at baseline; P = 0.8), the HF group (3.49 ± 1.43 at 6 weeks versus 3.26 ± 1.33 at baseline; P = 0.8) or the LF group (3.76 ± 2.01 at 6 weeks versus 3.56 ± 1.81 at baseline; P = 0.8). Interventions were safe and well-tolerated with no treatment-attributed serious adverse events. We provide proof of concept for the use of a single-dose oral FMT combined with daily low-fermentable fiber supplementation to improve insulin sensitivity in patients with severe obesity and metabolic syndrome.}, }
@article {pmid34226711, year = {2021}, author = {Montassier, E and Valdés-Mas, R and Batard, E and Zmora, N and Dori-Bachash, M and Suez, J and Elinav, E}, title = {Probiotics impact the antibiotic resistance gene reservoir along the human GI tract in a person-specific and antibiotic-dependent manner.}, journal = {Nature microbiology}, volume = {6}, number = {8}, pages = {1043-1054}, pmid = {34226711}, issn = {2058-5276}, support = {/WT_/Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacteria/classification/*drug effects/*genetics/isolation &amp; purification ; Bacterial Proteins/*genetics/metabolism ; Cohort Studies ; *Drug Resistance, Bacterial ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Gastrointestinal Tract/microbiology ; Humans ; Male ; Metagenome/drug effects ; Middle Aged ; Probiotics/*administration &amp; dosage ; Young Adult ; }, abstract = {Antimicrobial resistance poses a substantial threat to human health. The gut microbiome is considered a reservoir for potential spread of resistance genes from commensals to pathogens, termed the gut resistome. The impact of probiotics, commonly consumed by many in health or in conjunction with the administration of antibiotics, on the gut resistome is elusive. Reanalysis of gut metagenomes from healthy antibiotics-naïve humans supplemented with an 11-probiotic-strain preparation, allowing direct assessment of the gut resistome in situ along the gastrointestinal (GI) tract, demonstrated that probiotics reduce the number of antibiotic resistance genes exclusively in the gut of colonization-permissive individuals. In mice and in a separate cohort of humans, a course of antibiotics resulted in expansion of the lower GI tract resistome, which was mitigated by autologous faecal microbiome transplantation or during spontaneous recovery. In contrast, probiotics further exacerbated resistome expansion in the GI mucosa by supporting the bloom of strains carrying vancomycin resistance genes but not resistance genes encoded by the probiotic strains. Importantly, the aforementioned effects were not reflected in stool samples, highlighting the importance of direct sampling to analyse the effect of probiotics and antibiotics on the gut resistome. Analysing antibiotic resistance gene content in additional published clinical trials with probiotics further highlighted the importance of person-specific metagenomics-based profiling of the gut resistome using direct sampling. Collectively, these findings suggest opposing person-specific and antibiotic-dependent effects of probiotics on the resistome, whose contribution to the spread of antimicrobial resistance genes along the human GI tract merit further studies.}, }
@article {pmid34225483, year = {2021}, author = {Matsui, M and Fukunishi, S and Nakano, T and Ueno, T and Higuchi, K and Asai, A}, title = {Ileal Bile Acid Transporter Inhibitor Improves Hepatic Steatosis by Ameliorating Gut Microbiota Dysbiosis in NAFLD Model Mice.}, journal = {mBio}, volume = {12}, number = {4}, pages = {e0115521}, pmid = {34225483}, issn = {2150-7511}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Diet, High-Fat ; Disease Models, Animal ; Dysbiosis/microbiology/*prevention &amp; control ; Fatty Liver/microbiology/*prevention &amp; control ; Gastrointestinal Microbiome/genetics/*physiology ; Liver/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat deposition in the liver unrelated to alcohol consumption, is highly prevalent worldwide. However, effective therapeutic agents approved for NAFLD treatment are lacking. An ileal bile acid transporter inhibitor (IBATi), which represents a new mode of treatment of chronic idiopathic constipation, leads to increased delivery of bile acids to the colon. We investigated the effect of IBATi against NAFLD through modification of the gut microbiota in mice. IBATi treatment significantly suppressed body weight gain, liver dysfunction, and serum low-density lipoprotein levels and significantly decreased NAFLD activity scores in high-fat diet (HFD) mice. Treatment with IBATi ameliorated the decreased hepatic cholesterol 7-a-monooxygenase (Cyp7a1) and increased ileal fibroblast growth factor 15 (Fgf15) mRNA expression in HFD mice. Further, IBATi treatment changed the α-diversity in the gut microbiota reduced by HFD, which was analyzed in feces using 16S rRNA sequencing. To establish the mechanism underlying improvement in NAFLD induced by IBATi, we recolonized antibiotic solution-treated mice by fecal microbiome transplantation (FMT) using stool from HFD or HFD plus IBATi mice. This is the first report that fecally transplanted gut microbiota from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. In conclusion, IBATi improved hepatic steatosis by ameliorating gut microbiota dysbiosis in NAFLD model mice, suggesting a potential therapeutic agent for NAFLD treatment. IMPORTANCE NAFLD is an increasingly recognized condition that may progress to liver cirrhosis and hepatocellular carcinoma, and community surveys have assessed that the prevalence is 14 to 32% worldwide. The first line of treatment for NAFLD is lifestyle modification to achieve weight reduction, particularly through diet and exercise. However, weight reduction is difficult to achieve and maintain, and pharmacological agents approved for the treatment of NAFLD are lacking. This study investigated the influence of the gut microbiota and the effect of an IBATi on NAFLD using a murine model. Treatment with IBATi significantly improved NAFLD in HFD mice. Further, fecal microbiome transplantation using stool from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. Our study makes a significant contribution to the literature because the study findings suggest a potential treatment strategy for NAFLD patients by ameliorating gut microbiota dysbiosis.}, }
@article {pmid34224741, year = {2021}, author = {Khoruts, A}, title = {Can FMT Cause or Prevent CRC? Maybe, But There Is More to Consider.}, journal = {Gastroenterology}, volume = {161}, number = {4}, pages = {1103-1105}, doi = {10.1053/j.gastro.2021.06.074}, pmid = {34224741}, issn = {1528-0012}, mesh = {*Clostridioides difficile ; *Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid34222145, year = {2021}, author = {Morello, W and D'Amico, F and Serafinelli, J and Turroni, S and Abati, I and Fiori, J and Baskin, E and Yalcinkaya, F and Jankauskiene, A and Pennesi, M and Zurowska, A and Becherucci, F and Drozdz, D and Mekahli, D and Krzemien, G and La Scola, C and Taranta-Janusz, K and Mehls, O and Schaefer, F and Candela, M and Montini, G}, title = {Low-Dose Antibiotic Prophylaxis Induces Rapid Modifications of the Gut Microbiota in Infants With Vesicoureteral Reflux.}, journal = {Frontiers in pediatrics}, volume = {9}, number = {}, pages = {674716}, pmid = {34222145}, issn = {2296-2360}, abstract = {Background and Objectives: Maturation of the gut microbiota (GM) in infants is critically affected by environmental factors, with potential long-lasting clinical consequences. Continuous low-dose antibiotic prophylaxis (CAP) is the standard of care for children with vesicoureteral reflux (VUR), in order to prevent recurrent urinary tract infections. We aimed to assess short-term GM modifications induced by CAP in infants. Methods: We analyzed the GM structure in 87 infants (aged 1-5 months) with high-grade VUR, previously exposed or naïve to CAP. Microbial DNA was extracted from stool samples. GM profiling was achieved by 16S rRNA gene-based next-generation sequencing. Fecal levels of short- and branched-chain fatty acids were also assessed. Results: 36/87 patients had been taking daily CAP for a median time of 47 days, while 51/87 had not. In all patients, the GM was predominantly composed by Bifidobacteriaceae and Enterobacteriaceae. Subgroup comparative analysis revealed alterations in the GM composition of CAP-exposed infants at phylum, family and genus level. CAP-exposed GM was enriched in members of Enterobacteriaceae and Bacteroidetes, especially in the genera Bacteroides and Parabacteroides, and showed a trend toward increased Klebsiella, often associated with antibiotic resistance. In contrast, the GM of non-CAP children was mostly enriched in Bifidobacterium. No differences were found in fatty acid levels. Conclusions: In infants with VUR, even a short exposure to CAP definitely alters the GM composition, with increased relative abundance of opportunistic pathogens and decreased proportions of health-promoting taxa. Early low-dose antibiotic exposure might bear potential long-term clinical risks.}, }
@article {pmid34222037, year = {2021}, author = {Tan, R and Dong, H and Chen, Z and Jin, M and Yin, J and Li, H and Shi, D and Shao, Y and Wang, H and Chen, T and Yang, D and Li, J}, title = {Intestinal Microbiota Mediates High-Fructose and High-Fat Diets to Induce Chronic Intestinal Inflammation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {654074}, pmid = {34222037}, issn = {2235-2988}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; Firmicutes ; Fructose ; *Gastrointestinal Microbiome ; Inflammation ; Mice ; Mice, Inbred C57BL ; }, abstract = {An unhealthy diet has been linked to increased incidence of chronic diseases. To investigate the relationship between diet and intestinal inflammation, mice in two experimental groups were fed on a high-fat diet or high-fructose diet, respectively. The result showed that the defecation volume of the experimental groups was significantly reduced compared with that of the control group, and the levels of pro-inflammatory cytokines (interleukin (IL)-1β and IL-6) and IgG in serum were increased significantly. In addition, inflammatory cell infiltration was observed in intestinal tissue, indicating that a high-fructose or high-fat diet can lead to constipation and inflammation. Further analysis showed that the microbial composition of the experimental groups changed significantly, including a decrease of the Bacteroidetes/Firmicutes ratio and increased levels of Bacteroides, Akkermansia, Lactobacillus, and Ruminococcus, which might be associated with inflammation. The results of pro-inflammatory metabolites analysis showed that the levels of arachidonic acid, stearic acid, and indoxylsulfuric acid were significantly increased in the experimental groups, which were related significantly to Bacteroides, Enterococcus, and Akkermansia. Meanwhile, the content of 5-hydroxytryptamine (5-HT) was significantly decreased, which might cause constipation by reducing intestinal peristalsis. Moreover, transplantation of fecal bacteria from inflammatory mice caused constipation and inflammation in normal mice, which could be relieved by feeding a normal diet. The results of the present study indicated that changes in intestinal microbiota and microbial metabolites may underlie chronic intestinal inflammation and constipation caused by high-fructose and high-fat diets.}, }
@article {pmid34221998, year = {2021}, author = {Liu, Y and Yang, C and Zhang, Z and Jiang, H}, title = {Gut Microbiota Dysbiosis Accelerates Prostate Cancer Progression Through Increased LPCAT1 Expression and Enhanced DNA Repair Pathways.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {679712}, pmid = {34221998}, issn = {2234-943X}, abstract = {Gut microbiota dysbiosis is related to cancer development and progression. Our previous study showed that Ruminococcus was more abundant in CRPC (Castration-resistant prostate cancer) than HSPC (Hormone-sensitive prostate cancer) individuals. Here, we determined the potential mechanism of microbiota dysbiosis in prostate cancer (PCa) progression. Metagenomics was used to verify the gut microbial discrepancies between CRPC and HSPC individuals. Fecal microbiota transplantation (FMT) was performed by transferring the fecal suspension of CRPC or HSPC individuals to TRAMP mice. Afterwards, the mice's prostate histopathology and gut microbiota composition were determined. Since Ruminococcus was demonstrated to correlate with phospholipid metabolism, we used lipidomics to examine the mice's fecal lipid profiles. The expression of LPCAT1 the key enzyme for phospholipid remodeling in mice prostate was also examined. Meanwhile, both microbial functions prediction and LPCAT1 GSEA analysis (Gene Set Enrichment Analysis) indicated DNA repair pathways, we further determined the expressions of RAD51 and DNA-PKcs in mice prostate. The results showed that gut Ruminococcus was significantly more abundant in CRPC individuals. FMT using CRPC feces accelerated mice's PCa progression and increased their gut Ruminococcus abundance. Majority of fecal lipids including lysophosphatidylcholine and phosphatidylcholine were upregulated in CRPC FMT treated mice, accompanied with enhanced expressions of LPCAT1, RAD51, and DNA-PKcs in mice prostate. We reported an abundant colonization of Ruminococcus in the gut of CRPC individuals and mice receiving their fecal suspensions, and revealed the promotive capability of Ruminococcus in PCa progression via upregulating LPCAT1 and DNA repair protein expressions. The bacterium and its downstream pathways may become the targets of therapies for PCa in the future.}, }
@article {pmid34220825, year = {2021}, author = {Zhao, Y and Li, X and Zhou, Y and Gao, J and Jiao, Y and Zhu, B and Wu, D and Qi, X}, title = {Safety and Efficacy of Fecal Microbiota Transplantation for Grade IV Steroid Refractory GI-GvHD Patients: Interim Results From FMT2017002 Trial.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {678476}, pmid = {34220825}, issn = {1664-3224}, mesh = {Adolescent ; Adult ; Clinical Decision-Making ; Disease Management ; Disease Susceptibility ; Drug Resistance ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Gastrointestinal Diseases/*diagnosis/etiology/*therapy ; Graft vs Host Disease/*diagnosis/etiology/*therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents/therapeutic use ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Severity of Illness Index ; Steroids/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {UNLABELLED: Gastrointestinal (GI) tract graft-versus-host disease (GvHD) is a major cause of post-allo-HSCT (hematopoietic stem cell transplantation) morbidity and mortality. Patients with steroid-refractory GI-GvHD have a poor prognosis and limited therapeutic options. FMT2017002 trial (#NCT03148743) was a non-randomized, open-label, phase I/II clinical study of FMT for treating patients with grade IV steroid-refractory GI-GvHD. A total of 55 patients with steroid-refractory GI-GvHD were enrolled in this study. Forty-one patients with grade IV steroid-refractory GI-GvHD were included in the final statistical analysis. Of them, 23 patients and 18 patients were assigned to the FMT group and the control group, respectively. On days 14 and 21 after FMT, clinical remission was significantly greater in the FMT group than in the control group. Within a follow-up period of 90 days, the FMT group showed a better overall survival (OS). At the end of the study, the median survival time was >539 days in the FMT group and 107 days in the control group (HR=3.51; 95% CI, 1.21-10.17; p=0.021). Both the event-free survival time (EFS) (HR=2.3, 95% CI, 0.99-5.4; p=0.08) and OS (HR=4.4, 95% CI, 1.5-13.04; p=0.008) were higher in the FMT group during the follow-up period. Overall, the mortality rate was lower in the FMT group (HR=3.97; 95% CI, 1.34-11.75; p=0.013). No differences in the occurrence of any other side effects were observed. Our data suggest that the diversity of the intestinal microbiota could be affected by allo-HSCT. Although its effectiveness and safety need further evaluation, FMT may serve as a therapeutic option for grade IV steroid-refractory GI-GvHD.<br><br>CLINICAL TRIAL REGISTRATION: [ClinicalTrials.gov], identifier [NCT03148743].}, }
@article {pmid34219519, year = {2021}, author = {Gallop, A and Weagley, J and Paracha, SU and Grossberg, G}, title = {The Role of The Gut Microbiome in Parkinson's Disease.}, journal = {Journal of geriatric psychiatry and neurology}, volume = {34}, number = {4}, pages = {253-262}, doi = {10.1177/08919887211018268}, pmid = {34219519}, issn = {0891-9887}, mesh = {Disease Progression ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; *Parkinson Disease ; }, abstract = {The gut microbiota is known to play a role in various disease states through inflammatory, immune and endocrinologic response. Parkinson's Disease is of particular interest as gastrointestinal involvement is one of the earlier features seen in this disease. This paper examines the relationship between gut microbiota and Parkinson's Disease, which has a growing body of literature. Inflammation caused by gut dysbiosis is thought to increase a-synuclein aggregation and worsen motor and neurologic symptoms of Parkinson's disease. We discuss potential treatment and supplementation to modify the microbiota. Some of these treatments require further research before recommendations can be made, such as cord blood transplant, antibiotic use, immunomodulation and fecal microbiota transplant. Other interventions, such as increasing dietary fiber, polyphenol and fermented food intake, can be made with few risks and may have some benefit for symptom relief and speed of disease progression.}, }
@article {pmid34214453, year = {2022}, author = {Watane, A and Cavuoto, KM and Rojas, M and Dermer, H and Day, JO and Banerjee, S and Galor, A}, title = {Fecal Microbial Transplant in Individuals With Immune-Mediated Dry Eye.}, journal = {American journal of ophthalmology}, volume = {233}, number = {}, pages = {90-100}, pmid = {34214453}, issn = {1879-1891}, support = {R01 EY026174/EY/NEI NIH HHS/United States ; P30 EY014801/EY/NEI NIH HHS/United States ; I01 BX004893/BX/BLRD VA/United States ; R61 EY032468/EY/NEI NIH HHS/United States ; I01 CX002015/CX/CSRD VA/United States ; }, mesh = {*Dry Eye Syndromes/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Male ; *Microbiota ; Middle Aged ; Treatment Outcome ; }, abstract = {PURPOSE: To evaluate the safety of the Fecal Microbial Transplant for Sjogren Syndrome (FMT) trial in individuals with immune-mediated dry eye (DE).<br><br>DESIGN: Open-label, nonrandomized clinical trial.<br><br>METHODS: The study population included 10 individuals with DE symptoms and signs meeting criteria for Sj&#xf6;gren or positive early Sj&#xf6;gren markers. Procedures were 2 FMTs from a single healthy donor delivered via enema, 1 week apart. The primary outcome measure was safety. In addition, gut microbiome profiles, DE metrics, and T-cell profiles in blood were examined at baseline before FMT, and at 1 week, 1 month, and 3 months after FMT.<br><br>RESULTS: The mean age of the population was 60.4 years; 30% were male; 50% were white; and 50% were Hispanic. At baseline, all subjects had significantly different gut microbiome profiles from the donor, including higher mean diversity indices. Subjects had a decreased abundance of genera Faecalibacterium, Prevotella, and Ruminococcus and an increased abundance of genera Alistipes, Streptococcus, and Blautia compared to the donor. Effector and regulatory T-cell profiles were positively correlated with each other and with DE symptom severity (T helper 1 cells [Th1]; r&#xa0;=&#xa0;.76; P&#xa0;=&#xa0;.01; Th17: r&#xa0;=&#xa0;0.83; P&#xa0;=&#xa0;.003; CD25: r&#xa0;=&#xa0;0.66; P&#xa0;=&#xa0;.04; FoxP3: r&#xa0;=&#xa0;0.68; P&#xa0;=&#xa0;.03). No adverse events were noted with FMT. After FMT, gut microbiome profiles in 8 subjects moved closer to the donor's profile. As a group, gut microbiome profiles at all follow-up time points were more similar to the original recipients' than the donor's microbiome; however, certain phyla, classes, and genera operational taxonomic unit (OTU) numbers remained closer to the donor vs recipients' baseline profiles out to 3 months. Five individuals subjectively reported improved dry eye symptoms 3 months after FMT.<br><br>CONCLUSIONS: FMT was safely performed in individuals with immune-mediated DE, with certain bacterial profiles resembling the donor out to 3 months after FMT. One-half the subjects reported improved DE symptoms. The most effective FMT administration method has yet to be determined.}, }
@article {pmid34213510, year = {2021}, author = {Dhere, T and Tager, D and Kilakkathi, SP and Woodworth, MH and Kraft, CS}, title = {Earlier use of fecal transplant administration during hospitalization for Clostridioides difficile infectionmay improve outcome.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {33}, number = {8}, pages = {1132-1133}, doi = {10.1097/MEG.0000000000002159}, pmid = {34213510}, issn = {1473-5687}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation ; Hospitalization ; Humans ; }, }
@article {pmid34212214, year = {2021}, author = {Gupta, M and Krishan, P and Kaur, A and Arora, S and Trehanpati, N and Singh, TG and Bedi, O}, title = {Mechanistic and physiological approaches of fecal microbiota transplantation in the management of NAFLD.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {70}, number = {7}, pages = {765-776}, pmid = {34212214}, issn = {1420-908X}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Humans ; Non-alcoholic Fatty Liver Disease/etiology/microbiology/*therapy ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a multifaceted disease allied with various metabolic disorders, obesity and dysbiosis. Gut microbiota plays an influential role in the pathogenesis of NAFLD and other metabolic disorders. However, recent scientific upsurge emphasizes on the utility of beneficial gut microbiota and bacteriotherapy in the management of NAFLD. Fecal microbiota transplantation (FMT) is the contemporary therapeutic approach with state-of-the-art methods for the treatment of NAFLD. Other potential therapies include probiotics and prebiotics supplements which are based on alteration of gut microbes to treat NAFLD. In this review, our major focus is on the pathological association of gut microbiota with progression of NAFLD, historical aspects and recent advances in FMT with possible intervention to combat NAFLD and its associated metabolic dysfunctions.}, }
@article {pmid34209573, year = {2021}, author = {Gopalakrishnan, V and Dozier, EA and Glover, MS and Novick, S and Ford, M and Morehouse, C and Warrener, P and Caceres, C and Hess, S and Sellman, BR and Cohen, TS}, title = {Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen.}, journal = {Microorganisms}, volume = {9}, number = {7}, pages = {}, pmid = {34209573}, issn = {2076-2607}, abstract = {The gut microbiota has emerged as a key mediator of human physiology, and germ-free mice have been essential in demonstrating a role for the microbiome in disease. Preclinical models using conventional mice offer the advantage of working with a mature immune system. However, optimal protocols for fecal microbiota transplant (FMT) engraftment in conventional mice are yet to be established. Conventional BALB/c mice were randomized to receive 3-day (3d) or 3-week (3w) antibiotic (ABX) regimen in their drinking water followed by 1 or 5-daily FMTs from a human donor. Fecal samples were collected longitudinally and characterized using 16S ribosomal RNA (rRNA) sequencing. Semi-targeted metabolomic profiling of fecal samples was also done with liquid chromatography-mass spectrometry (LC-MS). Lastly, we sought to confirm our findings in BKS mice. Recovery of baseline diversity scores were greatest in the 3d groups, driven by re-emergence of mouse commensal microbiota, whereas the most resemblance to donor microbiota was seen in the 3w + 5-FMT group. Amplicon sequence variants (ASVs) that were linked to the input material (human ASVs) engrafted to a significantly greater extent when compared to mouse ASVs in the 3-week groups but not the 3-day groups. Lastly, comparison of metabolomic profiles revealed distinct functional profiles by ABX regimen. These results indicate successful model optimization and emphasize the importance of ABX duration and frequency of FMT dosing; the most stable and reliable colonization by donor ASVs was seen in the 3wk + 5-FMT group.}, }
@article {pmid34207314, year = {2021}, author = {Dergham, J and Delerce, J and Bedotto, M and La Scola, B and Moal, V}, title = {Isolation of Viable SARS-CoV-2 Virus from Feces of an Immunocompromised Patient Suggesting a Possible Fecal Mode of Transmission.}, journal = {Journal of clinical medicine}, volume = {10}, number = {12}, pages = {}, pmid = {34207314}, issn = {2077-0383}, abstract = {(1) Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) excretion in stools is well documented by RT-PCR, but evidences that stools contain infectious particles are scarce. (2) Methods: After observing a Corona Virus 2019 Disease (COVID-19) epidemic cluster associated with a ruptured sewage pipe, we search for such a viable SARS-CoV-2 particle in stool by inoculating 106 samples from 46 patients. (3) Results: We successfully obtained two isolates from a unique patient with kidney transplantation under immunosuppressive therapy who was admitted for severe diarrhea. (4) Conclusions: This report emphasizes that SARS-CoV-2 is an enteric virus, and infectious virus particles can be isolated from the stool of immune-compromised patients like, in our case, kidney transplant recipient. Immune-compromised patients are likely to have massive multiplication of the virus in the gastrointestinal tract and this report suggests possible fecal transmission of SARS-CoV-2.}, }
@article {pmid34206663, year = {2021}, author = {Březina, J and Bajer, L and Wohl, P and Ďuricová, D and Hrabák, P and Novotný, A and Koželuhová, J and Lukáš, M and Mrázek, J and Fliegerová, KO and Kvasnová, S and Chahrazed, M and Mareš, J and Špičák, J and Drastich, P}, title = {Fecal Microbial Transplantation versus Mesalamine Enema for Treatment of Active Left-Sided Ulcerative Colitis-Results of a Randomized Controlled Trial.}, journal = {Journal of clinical medicine}, volume = {10}, number = {13}, pages = {}, pmid = {34206663}, issn = {2077-0383}, support = {16-27449A//Ministerstvo Zdravotnictv&#xed; Cesk&#xe9; Republiky/ ; }, abstract = {BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic inflammatory disease. Fecal microbial transplantation (FMT) is a promising alternative treatment.<br><br>METHODS: This multicenter, open-label, noninferiority trial randomized patients with active left-sided UC (Mayo score 4-10) equally to FMT or 5-aminosalicylic acid (5-ASA) enemas. FMT enemas were administered five times in the first week and then once weekly for 5 weeks. 5-ASA enemas were administered daily for 2 weeks and then every other day. The primary study endpoint was clinical remission, with a total Mayo score &#x2264;2 at week 12 with no subscore >1.<br><br>RESULTS: Sixty-one patients were screened; 45 were enrolled and randomized to FMT (n = 23) or 5-ASA (n = 22). Twenty-one FMT and 22 5-ASA patients completed at least the week 4 study visit and were included in the mITT analysis. Twelve FMT (57%) and eight 5-ASA patients achieved the primary study endpoint. FMT noninferiority with 10% margin was confirmed (95% CI: -7.6%, 48.9%). Adverse events occurred in 12 FMT (57%) and 13 5-ASA (59%) patients. Increased microbial diversity persisted 3 months after FMT.<br><br>CONCLUSION: FMT is an effective treatment for left-sided UC and increased recipient microbiome diversity. Targeted microbiome modification may improve FMT efficacy. Further investigation is needed to guide donor and patient selection.}, }
@article {pmid34204748, year = {2021}, author = {Paratore, M and Santopaolo, F and Cammarota, G and Pompili, M and Gasbarrini, A and Ponziani, FR}, title = {Fecal Microbiota Transplantation in Patients with HBV Infection or Other Chronic Liver Diseases: Update on Current Knowledge and Future Perspectives.}, journal = {Journal of clinical medicine}, volume = {10}, number = {12}, pages = {}, pmid = {34204748}, issn = {2077-0383}, abstract = {Liver disease and gut dysbiosis are strictly associated, and the pathophysiology of this bidirectional relationship has recently been the subject of several investigations. Growing evidence highlights the link between gut microbiota composition, impairment of the gut-liver axis, and the development or progression of liver disease. Therefore, the modulation of gut microbiota to maintain homeostasis of the gut-liver axis could represent a potential instrument to halt liver damage, modify the course of liver disease, and improve clinical outcomes. Among all the methods available to achieve this purpose, fecal microbiota transplantation (FMT) is one of the most promising, being able to directly reshape the recipient's gut microbial communities. In this review, we report the main characteristics of gut dysbiosis and its pathogenetic consequences in cirrhotic patients, discussing the emerging data on the application of FMT for liver disease in different clinical settings.}, }
@article {pmid34204274, year = {2021}, author = {Fianchi, F and Liguori, A and Gasbarrini, A and Grieco, A and Miele, L}, title = {Nonalcoholic Fatty Liver Disease (NAFLD) as Model of Gut-Liver Axis Interaction: From Pathophysiology to Potential Target of Treatment for Personalized Therapy.}, journal = {International journal of molecular sciences}, volume = {22}, number = {12}, pages = {}, pmid = {34204274}, issn = {1422-0067}, mesh = {Bile Acids and Salts/metabolism ; Biomarkers ; Disease Management ; *Disease Susceptibility ; Energy Metabolism ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*metabolism/microbiology ; Humans ; Liver/*metabolism/pathology ; Non-alcoholic Fatty Liver Disease/*etiology/*metabolism/pathology/therapy ; Permeability ; Precision Medicine/methods ; *Signal Transduction ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide, affecting both adults and children and will result, in the near future, as the leading cause of end-stage liver disease. Indeed, its prevalence is rapidly increasing, and NAFLD is becoming a major public health concern. For this reason, great efforts are needed to identify its pathogenetic factors and new therapeutic approaches. In the past decade, enormous advances understanding the gut-liver axis-the complex network of cross-talking between the gut, microbiome and liver through the portal circulation-have elucidated its role as one of the main actors in the pathogenesis of NAFLD. Indeed, evidence shows that gut microbiota is involved in the development and progression of liver steatosis, inflammation and fibrosis seen in the context of NAFLD, as well as in the process of hepatocarcinogenesis. As a result, gut microbiota is currently emerging as a non-invasive biomarker for the diagnosis of disease and for the assessment of its severity. Additionally, to its enormous diagnostic potential, gut microbiota is currently studied as a therapeutic target in NAFLD: several different approaches targeting the gut homeostasis such as antibiotics, prebiotics, probiotics, symbiotics, adsorbents, bariatric surgery and fecal microbiota transplantation are emerging as promising therapeutic options.}, }
@article {pmid34204263, year = {2021}, author = {Vacca, M and Celano, G and Lenucci, MS and Fontana, S and Forgia, FM and Minervini, F and Scarano, A and Santino, A and Dalfino, G and Gesualdo, L and De Angelis, M}, title = {In Vitro Selection of Probiotics, Prebiotics, and Antioxidants to Develop an Innovative Synbiotic (NatuREN G) and Testing Its Effect in Reducing Uremic Toxins in Fecal Batches from CKD Patients.}, journal = {Microorganisms}, volume = {9}, number = {6}, pages = {}, pmid = {34204263}, issn = {2076-2607}, support = {XUANRO4//Regione Puglia/ ; }, abstract = {We aimed to develop an innovative synbiotic formulation for use in reducing dysbiosis, uremic toxins (e.g., p-cresol and indoxyl sulfate), and, consequently, the pathognomonic features of patients with chronic kidney disease (CKD). Twenty-five probiotic strains, belonging to lactobacilli and Bifidobacterium, were tested for their ability to grow in co-culture with different vegetable (pomegranate, tomato, and grapes) sources of antioxidants and prebiotics (inulin, fructo-oligosaccharides, and β-glucans). Probiotics were selected based on the acidification rates and viable cell counts. Inulin and fructo-oligosaccharides reported the best prebiotic activity, while a pomegranate seed extract was initially chosen as antioxidant source. The investigation was also conducted in fecal batches from healthy and CKD subjects, on which metabolomic analyses (profiling volatile organic compounds and total free amino acids) were conducted. Two out of twenty-five probiotics were finally selected. After the stability tests, the selective innovative synbiotic formulation (named NatuREN G) comprised Bifidobacterium animalis BLC1, Lacticaseibacillus casei LC4P1, fructo-oligosaccharides, inulin, quercetin, resveratrol, and proanthocyanidins. Finally, NatuREN G was evaluated on fecal batches collected from CKD in which modified the viable cell densities of some cultivable bacterial patterns, increased the concentration of acetic acid and decane, while reduced the concentration of nonanoic acid, dimethyl trisulfide, and indoxyl sulfate.}, }
@article {pmid34203609, year = {2021}, author = {Pavel, FM and Vesa, CM and Gheorghe, G and Diaconu, CC and Stoicescu, M and Munteanu, MA and Babes, EE and Tit, DM and Toma, MM and Bungau, S}, title = {Highlighting the Relevance of Gut Microbiota Manipulation in Inflammatory Bowel Disease.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, pmid = {34203609}, issn = {2075-4418}, abstract = {Two different conditions are included in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), being distinguished by chronic recurrence of gut inflammation in persons that are genetically predisposed and subjected to environmental causative factors. The normal structure of the gut microbiome and its alterations in IBD were defined in several microbial studies. An important factor in the prolonged inflammatory process in IBD is the impaired microbiome or "dysbiosis". Thus, gut microbiome management is likely to be an objective in IBD treatment. In this review, we analyzed the existing data regarding the pathophysiological/therapeutic implications of intestinal microflora in the development and evolution of IBD. Furthermore, the main effects generated by the administration of probiotics, prebiotics, fecal transplantation, and phytochemicals supplementation were analyzed regarding their potential roles in improving the clinical and biochemical status of patients suffering from Crohn's disease (CD) and ulcerative colitis (UC), and are depicted in the sections/subsections of the present paper. Data from the literature give evidence in support of probiotic and prebiotic therapy, showing effects such as improving remission rate, improving macroscopic and microscopic aspects of IBD, reducing the pro-inflammatory cytokines and interleukins, and improving the disease activity index. Therefore, the additional benefits of these therapies should not be ignored as adjuvants to medical therapy.}, }
@article {pmid34203536, year = {2021}, author = {Özdirik, B and Müller, T and Wree, A and Tacke, F and Sigal, M}, title = {The Role of Microbiota in Primary Sclerosing Cholangitis and Related Biliary Malignancies.}, journal = {International journal of molecular sciences}, volume = {22}, number = {13}, pages = {}, pmid = {34203536}, issn = {1422-0067}, support = {1983 4/1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Bile Duct Neoplasms/genetics/*metabolism ; Cholangiocarcinoma/genetics/metabolism ; Cholangitis, Sclerosing/genetics/*metabolism ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Inflammatory Bowel Diseases/genetics/metabolism ; Mice ; }, abstract = {Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy characterized by biliary inflammation, cholestasis, and multifocal bile duct strictures. It is associated with high rates of progression to end-stage liver disease as well as a significant risk of cholangiocarcinoma (CCA), gallbladder cancer, and colorectal carcinoma. Currently, no effective medical treatment with an impact on the overall survival is available, and liver transplantation is the only curative treatment option. Emerging evidence indicates that gut microbiota is associated with disease pathogenesis. Several studies analyzing fecal and mucosal samples demonstrate a distinct gut microbiome in individuals with PSC compared to healthy controls and individuals with inflammatory bowel disease (IBD) without PSC. Experimental mouse and observational human data suggest that a diverse set of microbial functions may be relevant, including microbial metabolites and bacterial processing of pharmacological agents, bile acids, or dietary compounds, altogether driving the intrahepatic inflammation. Despite critical progress in this field over the past years, further functional characterization of the role of the microbiota in PSC and related malignancies is needed. In this review, we discuss the available data on the role of the gut microbiome and elucidate important insights into underlying pathogenic mechanisms and possible microbe-altering interventions.}, }
@article {pmid34203292, year = {2021}, author = {Szczyrek, M and Bitkowska, P and Chunowski, P and Czuchryta, P and Krawczyk, P and Milanowski, J}, title = {Diet, Microbiome, and Cancer Immunotherapy-A Comprehensive Review.}, journal = {Nutrients}, volume = {13}, number = {7}, pages = {}, pmid = {34203292}, issn = {2072-6643}, mesh = {Animals ; Anti-Bacterial Agents ; Antibodies, Monoclonal, Humanized ; Bacteria/immunology ; Diet/*methods ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunotherapy/*methods ; Neoplasms/*therapy ; Obesity ; Probiotics/therapeutic use ; Thiamine ; Vitamin D ; }, abstract = {The immune system plays a key role in cancer suppression. Immunotherapy is widely used as a treatment method in patients with various types of cancer. Immune checkpoint blockade using antibodies, such as anti-PD-1, anti-PD-L1, and anti-CTLA-4, is currently gaining popularity. A systematic literature search was executed, and all available data was summarized. This review shows that specific dietary patterns (such as, e.g., animal-based, vegetarian, or Mediterranean diet) alter the gut microbiome's composition. An appropriate intestinal microbiota structure might modulate the function of human immune system, which affects the bodily anti-cancer response. This paper shows also that specific bacteria species inhabiting the gastrointestinal tract can have a beneficial influence on the efficacy of immunotherapy. Antibiotics weaken gut bacteria and worsen the immune checkpoint blockers' efficacy, whereas a faecal microbiota transplant or probiotics supplementation may help restore bacterial balance in the intestine. Other factors (like vitamins, glucose, or BMI) change the cancer treatment response, as well. This review demonstrates that there is a strong association between one's diet, gut microbiome composition, and the outcome of immunotherapy. However, further investigation on this subject is required.}, }
@article {pmid34202257, year = {2021}, author = {Kao, TW and Huang, CC}, title = {Recent Progress in Metabolic Syndrome Research and Therapeutics.}, journal = {International journal of molecular sciences}, volume = {22}, number = {13}, pages = {}, pmid = {34202257}, issn = {1422-0067}, support = {V109C-076//Taipei Veterans General Hospital/ ; MOST 108-2314-B-075-062-MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {Animals ; COVID-19/pathology/virology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Metabolic Syndrome/metabolism/pathology/*therapy ; Metabolomics ; Precision Medicine ; Proteomics ; SARS-CoV-2/isolation &amp; purification ; }, abstract = {Metabolic syndrome (MetS) is a well-defined yet difficult-to-manage disease entity. Both the precipitous rise in its incidence due to contemporary lifestyles and the growing heterogeneity among affected populations present unprecedented challenges. Moreover, the predisposed risk for developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in populations with MetS, and the viral impacts on host metabolic parameters, underscores the need to investigate this mechanism thoroughly. Recent investigations of metabolomics and proteomics have revealed not only differentially expressed substances in MetS, but also the consequences of diet consumption and physical activity on energy metabolism. These variations in metabolites, as well as protein products, also influence a wide spectrum of host characteristics, from cellular behavior to phenotype. Research on the dysregulation of gut microbiota and the resultant inflammatory status has also contributed to our understanding of the underlying pathogenic mechanisms. As for state-of-the-art therapies, advancing depictions of the bio-molecular landscape of MetS have emerged and now play a key role in individualized precision medicine. Fecal microbiota transplantation, aiming to restore the host's homeostasis, and targeting of the bile acid signaling pathway are two approaches to combatting MetS. Comprehensive molecular inquiries about MetS by omics measures are mandatory to facilitate the development of novel therapeutic modalities.}, }
@article {pmid34202210, year = {2021}, author = {Villoslada-Blanco, P and Pérez-Matute, P and Oteo, JA}, title = {Lights and Shadows of Microbiota Modulation and Cardiovascular Risk in HIV Patients.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {13}, pages = {}, pmid = {34202210}, issn = {1660-4601}, mesh = {*Cardiovascular Diseases/epidemiology/prevention &amp; control ; *HIV Infections ; Heart Disease Risk Factors ; Humans ; *Microbiota ; Risk Factors ; }, abstract = {Human immunodeficiency virus (HIV) infection is associated with premature aging and the development of aging-related comorbidities, such as cardiovascular disease (CVD). Gut microbiota (GM) disturbance is involved in these comorbidities and there is currently interest in strategies focused on modulating GM composition and/or functionality. Scientific evidence based on well-designed clinical trials is needed to support the use of prebiotics, probiotics, symbiotics, and fecal transplantation (FT) to modify the GM and reduce the incidence of CVD in HIV-infected patients. We reviewed the data obtained from three clinical trials focused on prebiotics, 25 trials using probiotics, six using symbiotics, and four using FT. None of the trials investigated whether these compounds could reduce CVD in HIV patients. The huge variability observed in the type of compound as well as the dose and duration of administration makes it difficult to adopt general recommendations and raise serious questions about their application in clinical practice.}, }
@article {pmid34199428, year = {2021}, author = {Akutko, K and Stawarski, A}, title = {Probiotics, Prebiotics and Synbiotics in Inflammatory Bowel Diseases.}, journal = {Journal of clinical medicine}, volume = {10}, number = {11}, pages = {}, pmid = {34199428}, issn = {2077-0383}, abstract = {Inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the digestive tract with periods of remission and relapses. The etiopathogenesis of IBD is multifactorial and has not been fully understood. Hence, only symptomatic treatment of these diseases is possible. The current pharmacological treatment has variable efficacy and is associated with the risk of significant side effects. Therefore, there is a constant need to search for new types of therapies with a high safety profile. Considering that the qualitative and quantitative profile of the gastrointestinal microbiome is often different in patients with IBD than in healthy individuals, there is a need for looking for therapies aimed at restoring intestinal microbiome homeostasis. Thus, the use of strictly defined probiotics, prebiotics and synbiotics may become an alternative form of IBD therapy. There is evidence that treatment with certain probiotic strains, e.g., VSL#3 and Escherischia coli Nissle 1917, is an effective form of therapy to induce remission in patients with mild to moderate UC. So far, the effectiveness of the use of probiotics, prebiotics and synbiotics in inducing or maintaining remission in patients with CD has not been confirmed. There are also reports of possible beneficial effects of fecal microbiota transplantation (FMT) on the course of IBD, especially UC. Further, well-planned studies on a large group of patients are needed to determine the role of specific probiotic strains, prebiotics, synbiotics and FMT in the treatment of IBD in adults and in children.}, }
@article {pmid34196310, year = {2021}, author = {Ghezzi, L and Cantoni, C and Pinget, GV and Zhou, Y and Piccio, L}, title = {Targeting the gut to treat multiple sclerosis.}, journal = {The Journal of clinical investigation}, volume = {131}, number = {13}, pages = {}, pmid = {34196310}, issn = {1558-8238}, support = {R01 NS102633/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Autoimmunity ; Disease Models, Animal ; Dysbiosis/immunology/physiopathology ; Endocrine System/immunology/physiopathology ; Enteric Nervous System/immunology/microbiology/physiopathology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/immunology/physiology ; Humans ; Intestinal Mucosa/immunology/microbiology/physiopathology ; Models, Neurological ; Multiple Sclerosis/etiology/microbiology/*therapy ; Neuroimmunomodulation ; Probiotics/therapeutic use ; }, abstract = {The gut-brain axis (GBA) refers to the complex interactions between the gut microbiota and the nervous, immune, and endocrine systems, together linking brain and gut functions. Perturbations of the GBA have been reported in people with multiple sclerosis (pwMS), suggesting a possible role in disease pathogenesis and making it a potential therapeutic target. While research in the area is still in its infancy, a number of studies revealed that pwMS are more likely to exhibit altered microbiota, altered levels of short chain fatty acids and secondary bile products, and increased intestinal permeability. However, specific microbes and metabolites identified across studies and cohorts vary greatly. Small clinical and preclinical trials in pwMS and mouse models, in which microbial composition was manipulated through the use of antibiotics, fecal microbiota transplantation, and probiotic supplements, have provided promising outcomes in preventing CNS inflammation. However, results are not always consistent, and large-scale randomized controlled trials are lacking. Herein, we give an overview of how the GBA could contribute to MS pathogenesis, examine the different approaches tested to modulate the GBA, and discuss how they may impact neuroinflammation and demyelination in the CNS.}, }
@article {pmid34196224, year = {2021}, author = {Long, D and Merlin, D}, title = {Micro- and nanotechnological delivery platforms for treatment of dysbiosis-related inflammatory bowel disease.}, journal = {Nanomedicine (London, England)}, volume = {16}, number = {20}, pages = {1741-1745}, pmid = {34196224}, issn = {1748-6963}, support = {BX002526, BX004476//U.S. Department of Veterans Affairs/ ; I01 BX002526/BX/BLRD VA/United States ; R01 DK107739/DK/NIDDK NIH HHS/United States ; #689659//Research Fellowship Award from the Crohn's and Colitis Foundation of America/ ; IK6 BX004476/BX/BLRD VA/United States ; RO1-DK-107739, RO1-DK-116306/DK/NIDDK NIH HHS/United States ; R01 DK116306/DK/NIDDK NIH HHS/United States ; }, mesh = {*Colitis ; Dysbiosis/drug therapy ; Humans ; *Inflammatory Bowel Diseases/drug therapy ; }, }
@article {pmid34191698, year = {2022}, author = {Wang, X and Liang, Z and Wang, S and Ma, D and Zhu, M and Feng, J}, title = {Role of Gut Microbiota in Multiple Sclerosis and Potential Therapeutic Implications.}, journal = {Current neuropharmacology}, volume = {20}, number = {7}, pages = {1413-1426}, pmid = {34191698}, issn = {1875-6190}, support = {2017YFC011304//National Key R&amp;D Program of China/ ; 31600820//National Natural Science Foundation of China/ ; 20180520110JH//Science and Technology planning project of Jilin Province/ ; }, mesh = {Animals ; Autoimmunity ; Dysbiosis ; *Encephalomyelitis, Autoimmune, Experimental/drug therapy ; *Gastrointestinal Microbiome ; Humans ; *Multiple Sclerosis/therapy ; }, abstract = {The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota have also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.}, }
@article {pmid34190675, year = {2022}, author = {Bibbò, S and Ianiro, G and Giambò, F and Settanni, CR and Cammarota, G and Gasbarrini, A}, title = {Role of gut microbiome on immunotherapy efficacy in melanoma.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {18}, number = {3}, pages = {1926759}, pmid = {34190675}, issn = {2164-554X}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunologic Factors ; Immunotherapy ; *Melanoma/therapy ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {The gut microbiota is considered a key component in many aspects of cancer pathophysiology and response to therapy. In particular, in recent years intriguing evidences has been emerging regarding the role of the intestinal microbiota in the response to immunotherapy and in promoting the development of adverse events, such as colitis. For this reason, studies are being carried out both on pre-clinical models and on humans to study how to predict the response to immunotherapy through the study of the microbiota or how to improve its clinical response through modulation. Promising data have recently been reported through modulation by probiotics or prebiotics, and in particular by fecal microbiota transplantation. The aim of this review is to analyze the evidence regarding the role of the microbiota in immunotherapy with a particular focus on melanoma.}, }
@article {pmid34189475, year = {2021}, author = {Choo, JM and Rogers, GB}, title = {Gut microbiota transplantation for colonization of germ-free mice.}, journal = {STAR protocols}, volume = {2}, number = {3}, pages = {100610}, pmid = {34189475}, issn = {2666-1667}, mesh = {Anaerobiosis ; Animals ; Bioreactors ; *Fecal Microbiota Transplantation ; Germ-Free Life ; Mice ; }, abstract = {The use of germ-free mice is integral to the understanding of host-gut microbiome relationships. Such models rely on faithful replication of the donor microbiome to establish causal effects of the gut microbiota on host pathophysiology. This protocol describes the preparation and transfer of donor microbiota, focusing on strict anaerobic processing methods and multiple instillations by gavage for optimal gut microbiota recovery. For complete details on the generation and use of this protocol, please refer to Choo and Rogers (2021).}, }
@article {pmid34186487, year = {2021}, author = {Wilson, BC and Butler, &#xc9;M and Grigg, CP and Derraik, JGB and Chiavaroli, V and Walker, N and Thampi, S and Creagh, C and Reynolds, AJ and Vatanen, T and O'Sullivan, JM and Cutfield, WS}, title = {Oral administration of maternal vaginal microbes at birth to restore gut microbiome development in infants born by caesarean section: A pilot randomised placebo-controlled trial.}, journal = {EBioMedicine}, volume = {69}, number = {}, pages = {103443}, pmid = {34186487}, issn = {2352-3964}, mesh = {Administration, Oral ; Adult ; Bacteroides/pathogenicity ; Cesarean Section/*adverse effects ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/etiology/*microbiology/prevention &amp; control ; Vagina/*microbiology ; }, abstract = {BACKGROUND: Birth by caesarean section (CS) is associated with aberrant gut microbiome development and greater disease susceptibility later in life. We investigated whether oral administration of maternal vaginal microbiota to infants born by CS could restore their gut microbiome development in a pilot single-blinded, randomised placebo-controlled trial (Australian New Zealand Clinical Trials Registry, ACTRN12618000339257).<br><br>METHODS: Pregnant women scheduled for a CS underwent comprehensive antenatal pathogen screening. At birth, healthy neonates were randomised to receive a 3&#xa0;ml solution of either maternal vaginal microbes (CS-seeded, n&#xa0;=&#xa0;12) or sterile water (CS-placebo, n&#xa0;=&#xa0;13). Vaginally-born neonates were used as the reference control (VB, n&#xa0;=&#xa0;22). Clinical assessments occurred within the first 2&#xa0;h of birth, and at 1 month and 3 months of age. Infant stool samples and maternal vaginal extracts from CS women underwent shotgun metagenomic sequencing. The primary outcome was gut microbiome composition at 1 month of age. Secondary outcomes included maternal strain engraftment, functional potential of the gut microbiome, anthropometry, body composition, and adverse events.<br><br>FINDINGS: Despite the presence of viable microbial cells within transplant solutions, there were no observed differences in gut microbiome composition or functional potential between CS-seeded and CS-placebo infants at 1 month or 3 months of age. Both CS groups displayed the characteristic signature of low Bacteroides abundance, which contributed to a number of biosynthesis pathways being underrepresented when compared with VB microbiomes. Maternal vaginal strain engraftment was rare. Vaginal seeding had no observed effects on anthropometry or body composition. There were no serious adverse events associated with treatment.<br><br>INTERPRETATION: Our pilot findings question the value of vaginal seeding given that oral administration of maternal vaginal microbiota did not alter early gut microbiome development in CS-born infants. The limited colonisation of maternal vaginal strains suggest that other maternal sources, such as the perianal area, may play a larger role in seeding the neonatal gut microbiome.<br><br>FUNDING: Health Research Council of New Zealand, A Better Start - National Science Challenge.}, }
@article {pmid34182544, year = {2021}, author = {Liu, M and Song, S and Chen, Q and Sun, J and Chu, W and Zhang, Y and Ji, F}, title = {Gut microbiota mediates cognitive impairment in young mice after multiple neonatal exposures to sevoflurane.}, journal = {Aging}, volume = {13}, number = {12}, pages = {16733-16748}, pmid = {34182544}, issn = {1945-4589}, mesh = {Anesthesia ; Animals ; Anti-Bacterial Agents/pharmacology ; Behavior, Animal ; Cognitive Dysfunction/*microbiology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/drug effects ; Germ-Free Life ; Mice, Inbred C57BL ; Morris Water Maze Test ; Pregnancy ; Prenatal Exposure Delayed Effects/*microbiology ; Sevoflurane/*adverse effects ; Mice ; }, abstract = {Multiple exposures to anesthesia may increase the risk of cognitive impairment in young children. However, the mechanisms underlying this neurodevelopmental disorder remain elusive. In this study, we investigated alteration of the gut microbiota after multiple neonatal exposures to the anesthetic sevoflurane and the potential role of microbiota alteration on cognitive impairment using a young mice model. Multiple neonatal sevoflurane exposures resulted in obvious cognitive impairment symptoms and altered gut microbiota composition. Fecal transplantation experiments confirmed that alteration of the microbiota was responsible for the cognitive disorders in young mice. Microbiota profiling analysis identified microbial taxa that showed consistent differential abundance before and after fecal microbiota transplantation. Several of the differentially abundant taxa are associated with memory and/or health of the host, such as species of Streptococcus, Lachnospiraceae, and Pseudoflavonifractor. The results reveal that abnormal composition of the gut microbiota is a risk factor for cognitive impairment in young mice after multiple neonatal exposures to sevoflurane and provide insight into a potential therapeutic strategy for sevoflurane-related neurotoxicity.}, }
@article {pmid34179058, year = {2021}, author = {Yu, Y and Cao, Y and Huang, W and Liu, Y and Lu, Y and Zhao, J}, title = {β-Sitosterol Ameliorates Endometrium Receptivity in PCOS-Like Mice: The Mediation of Gut Microbiota.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {667130}, pmid = {34179058}, issn = {2296-861X}, abstract = {Background: Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases in women of childbearing age, has been found to be accompanied by changes in the gut microbiota. The Bu Shen Yang Xue formula (BSYXF) is a traditional Chinese medicine widely used for the treatment of PCOS. This study aimed to investigate whether the protective effects of β-sitosterol, the main active ingredient of BSYXF, on PCOS was mediated by regulating gut microbiota. Methods: The presence of β-sitosterol in BSYXF was detected by liquid chromatography-mass spectrometry. The PCOS-like mouse model was induced by dehydroepiandrosterone. The fecal supernatant of β-sitosterol-treated mice was prepared for fecal microbiota transplantation (FMT). Body weight and wet weight of the uterus and ovary of the mice were recorded for organ index calculation. Hematoxylin and eosin stain was used to assess the endometrial morphology and microenvironment changes. Expression of endometrial receptivity markers cyclooxygenase-2 (COX-2), Integrin ανβ3, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) in the endometrium were determined by immunohistochemistry and western blot analysis. Enzyme-linked immunosorbent assay was employed to detect the expression of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and testosterone (T) in the serum. The diversity of gut microbiota was examined by 16S rDNA gene sequencing. Results: With the treatment of β-sitosterol and β-sitosterol-FMT, the uterine index of PCOS-like mice increased, the ovarian index decreased, levels of COX-2, LH and T decreased, and levels of Integrin ανβ3, LIF, HOXA10, FSH, and P increased. Under β-sitosterol treatment, the structure of the gut microbiota in PCOS-like mice was also changed. Conclusion: β-sitosterol regulates the endometrial receptivity of PCOS and harmonizes the sex hormone balance, which may be related to the changes in the structure and composition of gut microbiota, thus affecting the pathological process of PCOS.}, }
@article {pmid34178927, year = {2021}, author = {Vedala, K and Sobash, P and Shah, P and Kamoga, GR}, title = {Does Fecal Microbiota Transplant Have a Role in Treating Recurrent Clostridioides difficile Infection in Rural Hospitals?.}, journal = {Frontiers in public health}, volume = {9}, number = {}, pages = {670941}, pmid = {34178927}, issn = {2296-2565}, mesh = {Clostridioides ; *Clostridioides difficile ; Hospitals, Rural ; Humans ; *Microbiota ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection possesses a significant economical burden, specifically in the inpatient and rural settings. Fecal Microbiota Transplant has been used for treatment of recurrent Clostridioides difficile but its utility is limited by current guidelines and resources. We conducted a retrospective chart review to evaluate the financial benefit of using Fecal Microbiota Transplant after first recurrence of Clostridioides difficile infection. We found that while its use was restricted, on average Fecal Microbiota Transplant can save $11,603.49 per patient. In conclusion, our study shows that using Fecal Microbiota Transplant could prove to be economically beneficial in treating recurrent CDI in rural hospitals.}, }
@article {pmid34177852, year = {2021}, author = {Ma, X and Zhang, Y and Xu, T and Qian, M and Yang, Z and Zhan, X and Han, X}, title = {Early-Life Intervention Using Exogenous Fecal Microbiota Alleviates Gut Injury and Reduce Inflammation Caused by Weaning Stress in Piglets.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {671683}, pmid = {34177852}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) could shape the structure of intestinal microbiota in animals. This study was conducted to explore the changes that happen in the structure and function of microbiota caused by weaning stress, and whether early-life FMT could alleviate weaning stress through modifying intestinal microbiota in weaned piglets. Diarrheal (D) and healthy (H) weaned piglets were observed, and in the same farm, a total of nine litters newborn piglets were randomly allocated to three groups: sucking normally (S), weaned at 21 d (W), and early-life FMT + weaned at 21 d (FW). The results demonstrated that differences of fecal microbiota existed in group D and H. Early-life FMT significantly decreased diarrhea incidence of weaned piglets. Intestinal morphology and integrity were improved in the FW group. Both ZO-1 and occludin (tight junction proteins) of jejunum were greatly enhanced, while the zonulin expression was significantly down-regulated through early-life FMT. The expression of IL-6 and TNF-α (intestinal mucosal inflammatory cytokines) were down-regulated, while IL-10 (anti-inflammatory cytokines) was up-regulated by early-life FMT. In addition, early-life FMT increased the variety of the intestinal microbial population and the relative amounts of some beneficial bacteria such as Spirochaetes, Akkermansia, and Alistipes. Functional alteration of the intestinal microbiota revealed that lipid biosynthesis and aminoacyl-tRNA biosynthesis were enriched in the FW group. These findings suggested that alteration of the microbiota network caused by weaning stress induced diarrhea, and early-life FMT alleviated weaning stress in piglets, which was characterized by decreased diarrhea incidence, improved intestinal morphology, reduced intestinal inflammation, and modified intestinal bacterial composition and function.}, }
@article {pmid34177842, year = {2021}, author = {Koopen, AM and Almeida, EL and Attaye, I and Witjes, JJ and Rampanelli, E and Majait, S and Kemper, M and Levels, JHM and Schimmel, AWM and Herrema, H and Scheithauer, TPM and Frei, W and Dragsted, L and Hartmann, B and Holst, JJ and O'Toole, PW and Groen, AK and Nieuwdorp, M}, title = {Effect of Fecal Microbiota Transplantation Combined With Mediterranean Diet on Insulin Sensitivity in Subjects With Metabolic Syndrome.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {662159}, pmid = {34177842}, issn = {1664-302X}, abstract = {BACKGROUND: Recent studies demonstrate that a Mediterranean diet has beneficial metabolic effects in metabolic syndrome subjects. Since we have shown that fecal microbiota transplantation (FMT) from lean donors exerts beneficial effects on insulin sensitivity, in the present trial, we investigated the potential synergistic effects on insulin sensitivity of combining a Mediterranean diet with donor FMT in subjects with metabolic syndrome.<br><br>DESIGN: Twenty-four male subjects with metabolic syndrome were put on a Mediterranean diet and after a 2-week run-in phase, the subjects were randomized to either lean donor (n = 12) or autologous (n = 12) FMT. Changes in the gut microbiota composition and bacterial strain engraftment after the 2-week dietary regimens and 6 weeks post-FMT were the primary endpoints. The secondary objectives were changes in glucose fluxes (both hepatic and peripheral insulin sensitivity), postprandial plasma incretin (GLP-1) levels, subcutaneous adipose tissue inflammation, and plasma metabolites.<br><br>RESULTS: Consumption of the Mediterranean diet resulted in a reduction in body weight, HOMA-IR, and lipid levels. However, no large synergistic effects of combining the diet with lean donor FMT were seen on the gut microbiota diversity after 6 weeks. Although we did observe changes in specific bacterial species and plasma metabolites, no significant beneficial effects on glucose fluxes, postprandial incretins, or subcutaneous adipose tissue inflammation were detected.<br><br>CONCLUSIONS: In this small pilot randomized controlled trial, no synergistic beneficial metabolic effects of combining a Mediterranean diet with lean donor FMT on glucose metabolism were achieved. However, we observed engraftment of specific bacterial species. Future trials are warranted to test the combination of other microbial interventions and diets in metabolic syndrome.}, }
@article {pmid34176888, year = {2021}, author = {Feng, J and Tang, YN and Zhou, LX and Pan, JS}, title = {Standardized Nursing Procedures for Fecal Microbiota Transplantation via Upper Endoscopy.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {44}, number = {4}, pages = {227-232}, doi = {10.1097/SGA.0000000000000577}, pmid = {34176888}, issn = {1538-9766}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Gastroscopy ; Humans ; *Inflammatory Bowel Diseases ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation is an emerging treatment option that lacks a standardized nursing procedure. In our department, fecal microbiota transplantation has been undertaken to treat chronic hepatitis B and inflammatory bowel diseases since 2015. The fecal microbiota transplantation process involves various nursing measures that are critical for the successful completion of the procedures. In our center, a set of standardized nursing procedures has been established and has proved effective and operable. Standardized nursing procedures enhance the efficacy of fecal microbiota transplantation and alleviate the risk of treatment-related complications.}, }
@article {pmid34175104, year = {2021}, author = {Khanna, S}, title = {My Treatment Approach to Clostridioides difficile Infection.}, journal = {Mayo Clinic proceedings}, volume = {96}, number = {8}, pages = {2192-2204}, doi = {10.1016/j.mayocp.2021.03.033}, pmid = {34175104}, issn = {1942-5546}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridium/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; }, abstract = {Clostridioides difficile infection is the most common cause of infectious diarrhea in hospitals with an increasing incidence in the community. Clinical presentation of C difficile infection ranges from diarrhea manageable in the outpatient setting to fulminant infection requiring intensive care admission. There have been significant advances in the management of primary and recurrent C difficile infection including diagnostics, newer antibiotics, antibody treatments, and microbiome restoration therapies. Because of the risk of clinical false-positive results with the polymerase chain reaction test, a two-step assay combining an enzyme immune assay for glutamate dehydrogenase and the C difficile toxin is being used. Cost permitting, I treat a first episode of C difficile infection preferably with fidaxomicin over vancomycin but not metronidazole. The most common complication after C difficile infection is recurrence. I manage a first recurrence with a vancomycin taper and pulse or fidaxomicin and recommend a single dose of intravenous bezlotoxumab (a monoclonal antibody against the toxin B) to reduce recurrence rates for those patients at high risk. Patients with multiply recurrent C difficile infection are managed with a course of antibiotics such as vancomycin or fidaxomicin followed by microbiota restoration. The success of fecal microbiota transplantation is greater than 85%, compared with the 40% to 50% success rate of antibiotics in this situation. Fecal microbiota transplantation is heterogeneous and has rare but serious risks such as transmission of infections. Standardized microbiota restoration therapies are in clinical development and have completed phase III clinical trials. This review answers common clinical questions in the management of C difficile infection.}, }
@article {pmid34173726, year = {2021}, author = {Tan, Q and Orsso, CE and Deehan, EC and Kung, JY and Tun, HM and Wine, E and Madsen, KL and Zwaigenbaum, L and Haqq, AM}, title = {Probiotics, prebiotics, synbiotics, and fecal microbiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {14}, number = {9}, pages = {1820-1836}, doi = {10.1002/aur.2560}, pmid = {34173726}, issn = {1939-3806}, mesh = {*Autism Spectrum Disorder/therapy ; Behavioral Symptoms ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics/therapeutic use ; Randomized Controlled Trials as Topic ; *Synbiotics ; }, abstract = {The emerging role of a microbiota-gut-brain axis in autism spectrum disorder (ASD) suggests that modulating gut microbial composition may offer a tractable approach to addressing the lifelong challenges of ASD. The aim of this systematic review was to provide an overview and critically evaluate the current evidence on the efficacy and safety of probiotic, prebiotic, synbiotic, and fecal microbiota transplantation therapies for core and co-occurring behavioral symptoms in individuals with ASD. Comprehensive searches of MEDLINE, EMBASE, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar were performed from inception to March 5, 2020, and two update searches were completed on October 25, 2020, and April 22, 2021, respectively. A total of 4306 publications were identified, of which 14 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Results of probiotic studies do not confirm the supposed beneficial effect of probiotics on ASD, whereas prebiotics and synbiotic combinations appear to be efficacious in selective behavioral symptoms. Evidence of the efficacy of fecal microbiota transplantation in ASD is still scarce but supports further research. Overall, the current evidence base to suggest beneficial effects of these modalities in ASD is limited and inconclusive. More clinical trials are currently looking at the use of microbial-based therapies in ASD. With a robust double-blind randomized controlled protocol to investigate the efficacy, these trials should provide significant and definitive results. LAY SUMMARY: There is a link between altered gut bacteria and autism spectrum disorder. Some people believe that modulating bacterial composition in the gut may help reduce autism symptoms, but evidence from human studies suggesting beneficial effects of probiotic, prebiotic, and combination thereof as well as fecal transplants in autism spectrum disorder is limited and inconclusive. Current data should not encourage use of these modalities. Further clinical studies are needed.}, }
@article {pmid34172092, year = {2021}, author = {Zheng, H and Xu, P and Jiang, Q and Xu, Q and Zheng, Y and Yan, J and Ji, H and Ning, J and Zhang, X and Li, C and Zhang, L and Li, Y and Li, X and Song, W and Gao, H}, title = {Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {145}, pmid = {34172092}, issn = {2049-2618}, support = {21974096//National Natural Science Foundation of China/ ; 22074106//National Natural Science Foundation of China/ ; 81771386//National Natural Science Foundation of China/ ; 2018R52052//Ten-thousand Talents Program of Zhejiang Province/ ; QJD1802023//Qianjiang Talent Project of Zhejiang Province/ ; SQ2018YFE010015//National Key Research and Development Program/ ; }, mesh = {Acetates/pharmacology ; Animals ; Bacteria/genetics ; Brain ; *Cognitive Dysfunction ; *Diabetes Mellitus, Experimental ; *Gastrointestinal Microbiome ; Mice ; }, abstract = {BACKGROUND: Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism.<br><br>RESULTS: We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy.<br><br>CONCLUSIONS: Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline. Video Abstract.}, }
@article {pmid34171951, year = {2021}, author = {Špeciánová, &#x160;}, title = {[Legal aspects of intestinal microbiome application].}, journal = {Vnitrni lekarstvi}, volume = {67}, number = {E-3}, pages = {41-46}, pmid = {34171951}, issn = {0042-773X}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Application of intestinal microbiome (Fecal Microbiota Transplantation) is currently discussed treatment procedure which is the subject of professional interest not only when it comes to its medical aspects, but also its legal regulation. The aim of this article is to introduce a legal perspective on this subject matter and outline possible newly regulated areas. The subject matter is linked not only with the legislation contained in the Czech Civil Code in the section devoted to products having its origin in the human body, but also with other laws in the area of medical law. The position of regulatory authorities in the EU is also mentioned. It is apparent that EUs regulatory authorities leave this area for the legislation of individual EU member States.}, }
@article {pmid34170204, year = {2021}, author = {Dharmaratne, P and Rahman, N and Leung, A and Ip, M}, title = {Is there a role of faecal microbiota transplantation in reducing antibiotic resistance burden in gut? A systematic review and Meta-analysis.}, journal = {Annals of medicine}, volume = {53}, number = {1}, pages = {662-681}, pmid = {34170204}, issn = {1365-2060}, mesh = {*Drug Resistance, Microbial ; *Fecal Microbiota Transplantation ; Humans ; }, abstract = {OBJECTIVES: The aim of current systematic review and meta-analysis is to provide insight into the therapeutic efficacy of fecal microbiota transplantation (FMT) for the decolonization of antimicrobial-resistant (AMR) bacteria from the gut.<br><br>METHODS: The protocol for this Systematic Review was prospectively registered with PROSPERO&#xa0;(CRD42020203634). Four databases (EMBASE, MEDLINE, SCOPUS, and WEB of SCIENCE) were consulted up until September 2020. A total of fourteen studies [in vivo (n&#x2009;=&#x2009;2), case reports (n&#x2009;=&#x2009;7), case series without control arm (n&#x2009;=&#x2009;3), randomized clinical trials (RCT, n&#x2009;=&#x2009;2)], were reviewed. Data were synthesized narratively for the case reports, along with a proportion meta-analysis for the case series studies (n&#x2009;=&#x2009;102 subjects) without a control arm followed by another meta-analysis for case series studies with a defined control arm (n&#x2009;=&#x2009;111 subjects) for their primary outcomes.<br><br>RESULTS: Overall, seven non-duplicate case reports (n&#x2009;=&#x2009;9 participants) were narratively reviewed and found to have broad AMR remission events at the 1-month time point. Proportion meta-analysis of case series studies showed an overall 0.58 (95% CI: 0.42-0.74) AMR remission. Additionally, a significant difference in AMR remission was observed in FMT vs treatment na&#xef;ve (RR = 0.44; 95% CI: 0.20-0.99) and moderate heterogeneity (I[2]=65%). A subgroup analysis of RCTs (n&#x2009;=&#x2009;2) revealed FMT with further benefits of AMR remission with low statistical heterogeneity (RR = 0.37; 95% CI: 0.18-0.79; I[2] =23%).<br><br>CONCLUSION: More rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted.KEY MESSAGEExisting studies in this subject are limited and of low quality with moderate heterogeneity, and do not allow definitive conclusions to be drawn.More rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted.}, }
@article {pmid34169565, year = {2021}, author = {Fehily, SR and Basnayake, C and Wright, EK and Kamm, MA}, title = {Fecal microbiota transplantation therapy in Crohn's disease: Systematic review.}, journal = {Journal of gastroenterology and hepatology}, volume = {36}, number = {10}, pages = {2672-2686}, doi = {10.1111/jgh.15598}, pmid = {34169565}, issn = {1440-1746}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Crohn Disease/microbiology/physiopathology/therapy ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/physiology ; Humans ; Immunosuppressive Agents/adverse effects/therapeutic use ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: The gastrointestinal microbiota is the key antigenic drive in the inflammatory bowel diseases. Randomized controlled trials (RCTs) in ulcerative colitis have established fecal microbiota transplantation (FMT) as an effective therapy. We have conducted a systematic review to evaluate the efficacy of FMT in Crohn's disease.<br><br>METHODS: A systematic literature search was performed through to August 2020 (MEDLINE; Embase). Studies were included if they reported FMT administration in patients with Crohn's disease, and reported on clinical outcomes.<br><br>RESULTS: Fifteen studies published between 2014 and 2020, comprising 13 cohort studies and two RCTs, were included in the analysis. The majority of trials evaluated FMT for induction of remission, with follow-up duration varying from 4 to 52&#xa0;weeks. One RCT in 21 patients, of single-dose FMT versus placebo, following steroid-induced remission, showed a higher rate of steroid-free clinical remission in the FMT group compared to the control group: 87.5% vs 44.4% at week 10 (P&#xa0;=&#xa0;0.23). Another RCT, two-dose FMT in 31 patients, showed an overall clinical remission rate of 36% at week 8, however, with no difference in clinical or endoscopic endpoints between FMT administered by gastroscopy and colonoscopy. Considering all studies, the clinical response rates in early follow up were higher following multiple FMT than with single FMT. FMT dose did not appear to influence clinical outcomes, nor did whether FMT was fresh or frozen. FMT delivered via upper gastrointestinal route demonstrated higher early efficacy rates of 75 to 100% compared with lower delivery route rates of 30% to 58%, but on follow up beyond 8&#xa0;weeks, this difference was not maintained. Whether pre-FMT antibiotic administration was beneficial was not able to be determined due to the limited number of patients receiving antibiotics and varying antibiotic regimens. No serious adverse events were reported.<br><br>CONCLUSIONS: Preliminary studies suggest that FMT may be an effective therapy in Crohn's disease. However large controlled trials are needed. No serious safety concerns have been identified.}, }
@article {pmid34168881, year = {2021}, author = {Thomson, P and Núñez, P and Quera, R and Bay, C}, title = {Gastrointestinal microbiome, what is behind faecal microbiota transplantation?.}, journal = {New microbes and new infections}, volume = {42}, number = {}, pages = {100898}, pmid = {34168881}, issn = {2052-2975}, abstract = {The intestinal microbiota is made up of billions of microorganisms that coexist in an organised ecosystem, where strict and facultative anaerobic bacteria predominate. The alteration or imbalance of these microorganisms, known as dysbiosis, can be associated with both gastrointestinal and extraintestinal diseases. Based on a review of the literature, the intestinal microbiota is described in its state of health, the changes associated with some gastrointestinal diseases and the potential role that faecal microbiota transplantation has in the reestablishment of an altered ecosystem. Undoubtedly, the information revealed makes us reflect on the indication of faecal microbiota transplantation in various pathologies of intestinal origin. However, to ensure the efficacy and safety of this therapy, more studies are needed to obtain more evidence.}, }
@article {pmid34168535, year = {2021}, author = {Xu, X and Wang, K and Cao, X and Li, Z and Zhou, Y and Ren, J and Liu, F}, title = {Gut Microbial Metabolite Short-Chain Fatt Acids Partially Reverse Surgery and Anesthesia-Induced Behavior Deficits in C57BL/6J Mice.}, journal = {Frontiers in neuroscience}, volume = {15}, number = {}, pages = {664641}, pmid = {34168535}, issn = {1662-4548}, abstract = {Accumulating evidence has demonstrated that damages of gut microbiota are strongly associated with central nervous system (CNS) diseases, such as perioperative neurocognitive disorders (PND). The present study investigated the role of gut microbial metabolite short-chain fatty acids (SCFAs) in surgery-induced cognitive deficits and neuroinflammation in the hippocampus. Adult male C57BL/6J mice received either SCFA mixture or saline orally for 4 weeks, and then partial hepatectomy was performed. The fecal supernatant of surgical mice was transplanted to normal mice for 3 weeks. The Morris water maze (MWM) and open-field tests were used to evaluate behavioral performance on postoperative or post-transplantation days 3 and 7. In the MWM test, pretreatment with exogenous SCFAs partially reversed surgery-induced impairments in crossing times and the time spent in the target quadrant on postoperative day 3 (p < 0.05, p < 0.05, respectively). In the open-field test, compared with the surgical mice, exogenous SCFA administration prior to surgery partially improved the locomotor activity (p < 0.05) and anxiety-like behavior (p < 0.05) on postoperative day 3. Surgical trauma and anesthesia enhanced ionized calcium-binding adapter molecule 1 (Iba-1) expression (p < 0.001), increased the levels of interleukin (IL)-1β (p < 0.001) and IL-6 (p < 0.001), and inhibited SCFA production (p < 0.001) on postoperative day 3. The expression of the brain-derived neurotrophic factor (BDNF) was also decreased (p < 0.001). Overall, surgical trauma and anesthesia exacerbated cognitive impairment, enhanced neuroinflammatory responses, and inhibited SCFA production. Pretreatment with SCFAs attenuated these effects partially by reversing microglial overactivation, inhibiting neuroinflammatory responses, and enhancing BDNF expression.}, }
@article {pmid34168399, year = {2021}, author = {El-Salhy, M and Patcharatrakul, T and Gonlachanvit, S}, title = {Fecal microbiota transplantation for irritable bowel syndrome: An intervention for the 21[st] century.}, journal = {World journal of gastroenterology}, volume = {27}, number = {22}, pages = {2921-2943}, pmid = {34168399}, issn = {2219-2840}, mesh = {Diarrhea ; Fatty Acids, Volatile ; Fecal Microbiota Transplantation/adverse effects ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, abstract = {Irritable bowel syndrome (IBS) affects about 12% of the global population. Although IBS does not develop into a serious disease or increase mortality, it results in a considerable reduction in the quality of life. The etiology of IBS is not known, but the intestinal microbiota appears to play a pivotal role in its pathophysiology. There is no effective treatment for IBS, and so the applied treatments clinically focus on symptom relief. Fecal microbiota transplantation (FMT), an old Chinese treatment, has been applied to IBS patients in seven randomized controlled trials (RCTs). Positive effects on IBS symptoms in various degrees were obtained in four of these RCTs, while there was no effect in the remaining three. Across the seven RCTs there were marked differences in the selection processes for the donor and treated patients, the transplant dose, the route of administration, and the methods used to measure how the patients responded to FMT. The present frontier discusses these differences and proposes: (1) criteria for selecting an effective donor (superdonor); (2) selection criteria for patients that are suitable for FMT; (3) the optimal FMT dose; and (4) the route of transplant administration. FMT appears to be safe, with only mild, self-limiting side effects of abdominal pain, cramping, tenderness, diarrhea, and constipation. Although it is early to speculate about the mechanisms underlying the effects of FMT, the available data suggest that changes in the intestinal bacteria accompanied by changes in fermentation patterns and fermentation products (specifically short-chain fatty acids) play an important role in improving the IBS symptoms seen after FMT. FMT appears to be a promising treatment for IBS, but further studies are needed before it can be applied in everyday clinical practice.}, }
@article {pmid34168032, year = {2021}, author = {Hoffmann-Vold, AM and Fretheim, HH and Sarna, VK and Barua, I and Carstens, MN and Distler, O and Khanna, D and Volkmann, ER and Midtvedt, &#xd8; and Didriksen, H and Dhainaut, A and Halse, AK and Bakland, G and Pesonen, M and Olsen, I and Molberg, &#xd8;}, title = {Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial.}, journal = {BMJ open}, volume = {11}, number = {6}, pages = {e048541}, pmid = {34168032}, issn = {2044-6055}, mesh = {Anaerobiosis ; Clinical Trials, Phase II as Topic ; Double-Blind Method ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Los Angeles ; Multicenter Studies as Topic ; Pilot Projects ; Randomized Controlled Trials as Topic ; *Scleroderma, Systemic/therapy ; Treatment Outcome ; }, abstract = {INTRODUCTION: In the multisystem inflammatory disorder systemic sclerosis (SSc), gastrointestinal tract (GIT) affliction is highly prevalent. There are no known disease modifying therapies and the negative impact is substantial. Aiming for a new therapeutic principle, and inspired by recent work showing associations between gut microbiota changes and GIT symptoms in SSc, we performed a pilot study on faecal microbiota transplantation (FMT) with the single-donor bacterial culture 'Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)'. Motivated by positive pilot study signals, we designed the ReSScue trial as a phase II multicentre, placebo-controlled, randomised 20-week trial to evaluate safety and efficacy on lower GIT symptoms of FMT by ACHIM in SSc.<br><br>METHODS AND ANALYSES: We aim to include 70 SSc participants with moderate to severe lower GIT symptoms, defined by the validated patient-reported University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 2.0 questionnaire. The trial includes three parts. In part A1 (induction phase) lasting from week 0 to week 12, participants will be randomised 1:1 to repeat infusions of 30 mL ACHIM or placebo at week 0 and 2 by gastroduodenoscopy. In part A2, which is an 8-week subsequent maintenance phase, all study participants will receive 30 mL ACHIM at week 12 and followed until week 20 on continued blind. In part B, which will last until the last participant completes part A2, the participants will be followed through a maximum 16-week extended monitoring period, for longer-term data on safety and intervention effects. Primary endpoint is change from baseline to week 12 in UCLA GIT subscale scores of diarrhoea or bloating, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are safety measures and changes in UCLA GIT scores (total, diarrhoea and bloating).<br><br>ETHICS AND DISSEMINATION: This protocol was approved by the Northern Norwegian Committee for Medical Ethics. Study findings will be published.<br><br>TRIAL REGISTRATION NUMBER: NCT04300426; Pre-results.<br><br>PROTOCOL VERSION: V.3.1.}, }
@article {pmid34163471, year = {2021}, author = {Adda-Rezig, H and Carron, C and Pais de Barros, JP and Choubley, H and Charron, &#xc9; and Rérole, AL and Laheurte, C and Louvat, P and Gaiffe, &#xc9; and Simula-Faivre, D and Deckert, V and Lagrost, L and Saas, P and Ducloux, D and Bamoulid, J}, title = {New Insights on End-Stage Renal Disease and Healthy Individual Gut Bacterial Translocation: Different Carbon Composition of Lipopolysaccharides and Different Impact on Monocyte Inflammatory Response.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {658404}, pmid = {34163471}, issn = {1664-3224}, mesh = {Adult ; Aged ; *Bacterial Translocation ; Biomarkers ; Case-Control Studies ; Comorbidity ; Cytokines/blood ; Disease Management ; *Disease Susceptibility/immunology ; Endotoxemia/diagnosis/etiology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Inflammation Mediators/blood/metabolism ; Kidney Failure, Chronic/complications/diagnosis/*etiology/*therapy ; Kidney Transplantation ; Lipopolysaccharides/immunology/metabolism ; Male ; Middle Aged ; Monocytes/immunology/metabolism ; }, abstract = {Chronic kidney disease induces disruption of the intestinal epithelial barrier, leading to gut bacterial translocation. Here, we appreciated bacterial translocation by analyzing circulating lipopolysaccharides (LPS) using two methods, one measuring only active free LPS, and the other quantifying total LPS as well as LPS lipid A carbon chain length. This was done in end-stage renal disease (ESRD) patients and healthy volunteers (HV). We observed both higher LPS concentration in healthy volunteers and significant differences in composition of translocated LPS based on lipid A carbon chain length. Lower LPS activity to mass ratio and higher concentration of high-density lipoproteins were found in HV, suggesting a better plasma capacity to neutralize LPS activity. Higher serum concentrations of soluble CD14 and pro-inflammatory cytokines in ESRD patients confirmed this hypothesis. To further explore whether chronic inflammation in ESRD patients could be more related to LPS composition rather than its quantity, we tested the effect of HV and patient sera on cytokine secretion in monocyte cultures. Sera with predominance of 14-carbon chain lipid A-LPS induced higher secretion of pro-inflammatory cytokines than those with predominance of 18-carbon chain lipid A-LPS. TLR4 or LPS antagonists decreased LPS-induced cytokine production by monocytes, demonstrating an LPS-specific effect. Thereby, septic inflammation observed in ESRD patients may be not related to higher bacterial translocation, but to reduced LPS neutralization capacity and differences in translocated LPS subtypes.}, }
@article {pmid34163114, year = {2021}, author = {Nishida, A and Nishino, K and Sakai, K and Owaki, Y and Noda, Y and Imaeda, H}, title = {Can control of gut microbiota be a future therapeutic option for inflammatory bowel disease?.}, journal = {World journal of gastroenterology}, volume = {27}, number = {23}, pages = {3317-3326}, pmid = {34163114}, issn = {2219-2840}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy ; *Microbiota ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract encompassing two main clinical entities, Crohn's disease and ulcerative colitis. Accumulated evidence indicates that an aberrant immune activation caused by the interplay of genetic susceptibility and environmental impact on the gut microbiota may be involved in the pathogenesis of IBD. Rapid advances in next-generation sequencing technology have enabled a number of studies to identify the alteration of the gut microbiota, termed dysbiosis, in IBD. Moreover, the alteration in the metabolites derived from the gut microbiota in IBD has also been described in many studies. Therefore, microbiota-based interventions such as fecal microbiota transplantation (FMT) have attracted attention as a novel therapeutic option in IBD. However, in clinical trials, the efficacy of FMT for IBD remains controversial. Additional basic and clinical studies are required to validate whether FMT can assume a complementary role in the treatment of IBD. The present review provides a synopsis on dysbiosis in IBD and on the association between the gut microbiota and the pathogenesis of IBD. In addition, we summarize the use of probiotics in IBD and the results of current clinical trials of FMT for IBD.}, }
@article {pmid34163075, year = {2021}, author = {Delannoy-Bruno, O and Desai, C and Raman, AS and Chen, RY and Hibberd, MC and Cheng, J and Han, N and Castillo, JJ and Couture, G and Lebrilla, CB and Barve, RA and Lombard, V and Henrissat, B and Leyn, SA and Rodionov, DA and Osterman, AL and Hayashi, DK and Meynier, A and Vinoy, S and Kirbach, K and Wilmot, T and Heath, AC and Klein, S and Barratt, MJ and Gordon, JI}, title = {Evaluating microbiome-directed fibre snacks in gnotobiotic mice and humans.}, journal = {Nature}, volume = {595}, number = {7865}, pages = {91-95}, pmid = {34163075}, issn = {1476-4687}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; P30 DK056341/DK/NIDDK NIH HHS/United States ; DK078669/NH/NIH HHS/United States ; R25 GM103757/GM/NIGMS NIH HHS/United States ; P30 CA091842/CA/NCI NIH HHS/United States ; F30 DK124967/DK/NIDDK NIH HHS/United States ; R01 DK124193/DK/NIDDK NIH HHS/United States ; T32 GM007067/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; DK70977/NH/NIH HHS/United States ; T32 HL130357/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Animals ; Bacteroides/drug effects/isolation &amp; purification ; Blood Proteins/analysis ; Dietary Fiber/*pharmacology ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; *Germ-Free Life ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Obesity/microbiology ; Overweight/microbiology ; Proteome/analysis/drug effects ; *Snacks ; Young Adult ; }, abstract = {Changing food preferences brought about by westernization that have deleterious health effects[1,2]-combined with myriad forces that are contributing to increased food insecurity-are catalysing efforts to identify more nutritious and affordable foods[3]. Consumption of dietary fibre can help to prevent cardiovascular disease, type 2 diabetes and obesity[4-6]. A substantial number of reports have explored the effects of dietary fibre on the gut microbial community[7-9]. However, the microbiome is complex, dynamic and exhibits considerable intra- and interpersonal variation in its composition and functions. The large number of potential interactions between the components of the microbiome makes it challenging to define the mechanisms by which food ingredients affect community properties. Here we address the question of how foods containing different fibre preparations can be designed to alter functions associated with specific components of the microbiome. Because a marked increase in snack consumption is associated with westernization, we formulated snack prototypes using plant fibres from different sustainable sources that targeted distinct features of the gut microbiomes of individuals with obesity when transplanted into gnotobiotic mice. We used these snacks to supplement controlled diets that were consumed by adult individuals with obesity or who were overweight. Fibre-specific changes in their microbiomes were linked to changes in their plasma proteomes indicative of an altered physiological state.}, }
@article {pmid34162429, year = {2021}, author = {Hayase, E and Jenq, RR}, title = {Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer.}, journal = {Genome medicine}, volume = {13}, number = {1}, pages = {107}, pmid = {34162429}, issn = {1756-994X}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Antineoplastic Agents, Immunological/adverse effects/pharmacology/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Colitis/etiology ; Dysbiosis/etiology ; Gastrointestinal Microbiome/*drug effects/immunology ; Host Microbial Interactions/drug effects/immunology ; Humans ; Immune Checkpoint Inhibitors/adverse effects/*pharmacology/therapeutic use ; Metabolome/*drug effects ; Metabolomics/methods ; Models, Biological ; Neoplasms/*complications/drug therapy/immunology/metabolism ; }, abstract = {Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune inhibitory pathways. Administration of ICIs augments T cell-mediated immune responses against tumor, resulting in improved overall survival in cancer patients. It has emerged that the intestinal microbiome can modulate responses to ICIs via the host immune system and that the use of antibiotics can lead to reduced efficacy of ICIs. Recently, reports that fecal microbiota transplantation can lead to ICI therapy responses in patients previously refractory to therapy suggest that targeting the microbiome may be a viable strategy to reprogram the tumor microenvironment and augment ICI therapy. Intestinal microbial metabolites may also be linked to response rates to ICIs. In addition to response rates, certain toxicities that can arise during ICI therapy have also been found to be associated with the intestinal microbiome, including in particular colitis. A key mechanistic question is how certain microbes can enhance anti-tumor responses or, alternatively, predispose to ICI-associated colitis. Evidence has emerged that the intestinal microbiome can modulate outcomes to ICI therapies via two major mechanisms, including those that are antigen-specific and those that are antigen-independent. Antigen-specific mechanisms occur when epitopes are shared between microbial and tumor antigens that could enhance, or, alternatively, reduce anti-tumor immune responses via cross-reactive adaptive immune cells. Antigen-independent mechanisms include modulation of responses to ICIs by engaging innate and/or adaptive immune cells. To establish microbiome-based biomarkers of outcomes and specifically modulate the intestinal microbiome to enhance efficacy of ICIs in cancer immunotherapy, further prospective interventional studies will be required.}, }
@article {pmid34160593, year = {2021}, author = {Raine, T and Verstockt, B and Kopylov, U and Karmiris, K and Goldberg, R and Atreya, R and Burisch, J and Burke, J and Ellul, P and Hedin, C and Holubar, SD and Katsanos, K and Lobaton, T and Schmidt, C and Cullen, G}, title = {ECCO Topical Review: Refractory Inflammatory Bowel Disease.}, journal = {Journal of Crohn's &amp; colitis}, volume = {15}, number = {10}, pages = {1605-1620}, doi = {10.1093/ecco-jcc/jjab112}, pmid = {34160593}, issn = {1876-4479}, support = {//ECCO/ ; }, mesh = {Biological Factors/therapeutic use ; Diet ; Digestive System Surgical Procedures ; Fecal Microbiota Transplantation ; Gastrointestinal Agents/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents/therapeutic use ; Inflammatory Bowel Diseases/diagnosis/*therapy ; Medication Adherence ; Mesenchymal Stem Cell Transplantation ; Patient Care Team ; Remission Induction ; }, abstract = {Inflammatory bowel disease is a chronic disease with variable degrees of extent, severity, and activity. A proportion of patients will have disease that is refractory to licensed therapies, resulting in significant impairment in quality of life. The treatment of these patients involves a systematic approach by the entire multidisciplinary team, with particular consideration given to medical options including unlicensed therapies, surgical interventions, and dietetic and psychological support. The purpose of this review is to guide clinicians through this process and provide an accurate summary of the available evidence for different strategies.}, }
@article {pmid34158373, year = {2023}, author = {Kragsnaes, MS and Kjeldsen, J and Horn, HC and Munk, HL and Pedersen, JK and Just, SA and Ahlquist, P and Davidsen, JR and Nilsson, AC and Röttger, R and Kruhøffer, M and Marchesi, JR and Kristiansen, K and Christensen, R and Ellingsen, T}, title = {Response to: 'Correspondence on 'Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial'' by McGonagle et al.}, journal = {Annals of the rheumatic diseases}, volume = {82}, number = {7}, pages = {e165}, doi = {10.1136/annrheumdis-2021-220910}, pmid = {34158373}, issn = {1468-2060}, }
@article {pmid34158372, year = {2023}, author = {McGonagle, DG and Bridgewood, C and Marzo-Ortega, H}, title = {Correspondence on 'Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial'.}, journal = {Annals of the rheumatic diseases}, volume = {82}, number = {7}, pages = {e164}, doi = {10.1136/annrheumdis-2021-220871}, pmid = {34158372}, issn = {1468-2060}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *Arthritis, Psoriatic ; Fecal Microbiota Transplantation ; Treatment Outcome ; Randomized Controlled Trials as Topic ; }, }
@article {pmid34158061, year = {2021}, author = {Patrono, E and Svoboda, J and Stuchlík, A}, title = {Schizophrenia, the gut microbiota, and new opportunities from optogenetic manipulations of the gut-brain axis.}, journal = {Behavioral and brain functions : BBF}, volume = {17}, number = {1}, pages = {7}, pmid = {34158061}, issn = {1744-9081}, support = {CZ.02.2.69/0.0/0.0/19_074/0016409//European Science Foundation/ ; 20-00939S//Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; 21-16667K//Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; }, mesh = {Brain ; Brain-Gut Axis ; *Gastrointestinal Microbiome ; Humans ; Optogenetics ; *Probiotics ; *Schizophrenia/therapy ; }, abstract = {Schizophrenia research arose in the twentieth century and is currently rapidly developing, focusing on many parallel research pathways and evaluating various concepts of disease etiology. Today, we have relatively good knowledge about the generation of positive and negative symptoms in patients with schizophrenia. However, the neural basis and pathophysiology of schizophrenia, especially cognitive symptoms, are still poorly understood. Finding new methods to uncover the physiological basis of the mental inabilities related to schizophrenia is an urgent task for modern neuroscience because of the lack of specific therapies for cognitive deficits in the disease. Researchers have begun investigating functional crosstalk between NMDARs and GABAergic neurons associated with schizophrenia at different resolutions. In another direction, the gut microbiota is getting increasing interest from neuroscientists. Recent findings have highlighted the role of a gut-brain axis, with the gut microbiota playing a crucial role in several psychopathologies, including schizophrenia and autism.There have also been investigations into potential therapies aimed at normalizing altered microbiota signaling to the enteric nervous system (ENS) and the central nervous system (CNS). Probiotics diets and fecal microbiota transplantation (FMT) are currently the most common therapies. Interestingly, in rodent models of binge feeding, optogenetic applications have been shown to affect gut colony sensitivity, thus increasing colonic transit. Here, we review recent findings on the gut microbiota-schizophrenia relationship using in vivo optogenetics. Moreover, we evaluate if manipulating actors in either the brain or the gut might improve potential treatment research. Such research and techniques will increase our knowledge of how the gut microbiota can manipulate GABA production, and therefore accompany changes in CNS GABAergic activity.}, }
@article {pmid34154439, year = {2021}, author = {Drekonja, DM and Shaukat, A and Zhang, JH and Reinink, AR and Nugent, S and Dominitz, JA and Davis-Karim, A and Gerding, DN and Kyriakides, TC}, title = {Microbiota or placebo after antimicrobial therapy for recurrent Clostridioides difficile at home: A clinical trial with novel home-based enrollment.}, journal = {Clinical trials (London, England)}, volume = {18}, number = {5}, pages = {622-629}, doi = {10.1177/17407745211021198}, pmid = {34154439}, issn = {1740-7753}, mesh = {*Anti-Bacterial Agents/therapeutic use ; COVID-19 ; *Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Microbiota ; Quality of Life ; Recurrence ; Treatment Outcome ; }, abstract = {INTRODUCTION: Clostridiodes difficile infection is the leading cause of infectious diarrhea in the United States, with substantial morbidity and mortality. Recurrent infection is especially challenging, with each recurrence increasing the likelihood of a successive recurrence, leading to cycles of prolonged symptoms, frequent antimicrobial use, and decreased quality of life. Fecal microbiota transplantation to prevent recurrent infection is a promising intervention with a large effect size in observational studies, but with conflicting results from randomized controlled trials. We are conducting a Veterans Affairs-wide randomized controlled trial utilizing centralized case identification, with enrollment and fecal microbiota transplant administration occurring at the participant's home. This type of trial design significantly improves trial efficiency, greatly decreases trial cost, increases consistency of trial administration, and most importantly makes nationwide clinical trials in less-common diseases possible.<br><br>METHODS: This is a randomized comparison of capsule-delivered fecal microbiota transplant for the prevention of recurrent Clostridiodes difficile infection, administered after successful initial treatment of recurrent C. difficile infection with standard therapy. The primary endpoint is the incidence of recurrent C. difficile infection or death. Cases are identified by searching the Veterans Affairs Corporate Data Warehouse, with central study coordinators then reaching out to potential participants. Individuals meeting inclusion criteria and interested in participation are scheduled for in-home consent, randomization, and capsule administration, followed by telephone follow-up for 6&#x2009;months. To mitigate risks of COVID-19, enrollment via video visits has been implemented.<br><br>RESULTS: A total of 102 participants have been enrolled through January 2021. Centralized case identification and in-home enrollment has facilitated enrollment from 34 unique states, with 38% being from rural or highly rural areas.<br><br>DISCUSSION: Centralized case identification and in-home enrollment is a feasible and innovative method of conducting randomized controlled trials in the Veterans Affairs system, improving access to clinical research for populations who may have difficulty engaging with the traditional model of clinical trials where enrollment is based at large hospitals in major metropolitan areas.}, }
@article {pmid34153321, year = {2021}, author = {Thomaz, AC and Iyer, V and Woodward, TJ and Hohmann, AG}, title = {Fecal microbiota transplantation and antibiotic treatment attenuate naloxone-precipitated opioid withdrawal in morphine-dependent mice.}, journal = {Experimental neurology}, volume = {343}, number = {}, pages = {113787}, pmid = {34153321}, issn = {1090-2430}, support = {R01 DA041229/DA/NIDA NIH HHS/United States ; R01 DA047858/DA/NIDA NIH HHS/United States ; R21 DA042584/DA/NIDA NIH HHS/United States ; T32 DA024628/DA/NIDA NIH HHS/United States ; }, mesh = {Analgesics, Opioid/administration &amp; dosage ; Animals ; Anti-Bacterial Agents/*administration &amp; dosage ; Combined Modality Therapy/methods ; Fecal Microbiota Transplantation/*methods ; Male ; Mice ; Mice, Inbred C57BL ; Morphine Dependence/drug therapy/metabolism/*therapy ; Naloxone/*toxicity ; Narcotic Antagonists/*toxicity ; Probiotics/administration &amp; dosage ; Substance Withdrawal Syndrome/drug therapy/metabolism/*therapy ; }, abstract = {Opioid addiction can produce severe side effects including physical dependence and withdrawal. Perturbations of the gut microbiome have recently been shown to alter opioid-induced side-effects such as addiction, tolerance and dependence. In the present study, we investigated the influence of the gut microbiome on opioid withdrawal by evaluating the effects of fecal microbiota transplantation (FMT), antibiotic and probiotic treatments, and pharmacological inhibition of gut permeability in a mouse model of opioid dependence. Repeated intraperitoneal (i.p.) morphine treatment produced physical dependence that was quantified by measuring somatic signs of withdrawal (i.e. number of jumps) precipitated using the opioid antagonist naloxone. Morphine-dependent mice that received FMT from morphine-treated donor mice exhibited fewer naloxone-precipitated jumps compared to morphine-dependent counterparts receiving FMT from saline-treated donor mice. Microbial contents in the mouse cecum were altered by morphine treatment but were not differentially impacted by FMT. A broad-spectrum antibiotic cocktail (ABX) regimen reduced the bacterial load and attenuated naloxone-precipitated morphine withdrawal in morphine-dependent mice, whereas commercially available probiotic strains did not reliably alter somatic signs of opioid withdrawal. ML-7, a pharmacological inhibitor of gut permeability, reduced the morphine-induced increase in gut permeability in vivo but did not reliably alter somatic signs of naloxone-precipitated opioid withdrawal. Our results suggest that the gut microbiome impacts the development of physical dependence induced by chronic morphine administration, and that therapeutic manipulations of the gut microbiome may reduce opioid withdrawal.}, }
@article {pmid34152776, year = {2021}, author = {Yan, X and Ren, X and Liu, X and Wang, Y and Ma, J and Song, R and Wang, X and Dong, Y and Fan, Q and Wei, J and Yu, A and She, G}, title = {Dietary Ursolic Acid Prevents Alcohol-Induced Liver Injury via Gut-Liver Axis Homeostasis Modulation: The Key Role of Microbiome Manipulation.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {25}, pages = {7074-7083}, doi = {10.1021/acs.jafc.1c02362}, pmid = {34152776}, issn = {1520-5118}, mesh = {Animals ; *Chemical and Drug Induced Liver Injury, Chronic ; *Gastrointestinal Microbiome ; Homeostasis ; Liver ; *Liver Diseases, Alcoholic/drug therapy/prevention &amp; control ; Mice ; *Triterpenes ; Ursolic Acid ; }, abstract = {Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut-liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.}, }
@article {pmid34152347, year = {2021}, author = {Deng, L and Zeng, H and Hu, X and Xiao, M and He, D and Zhang, Y and Jin, Y and Hu, Y and Zhu, Y and Gong, L and Wang, Z and Xiang, L and Zhu, R and Zhang, Y and Cheng, Y and Chen, X and Zhang, S and Peng, Y and Cao, K}, title = {Se@Albumin nanoparticles ameliorate intestinal mucositis caused by cisplatin via gut microbiota-targeted regulation.}, journal = {Nanoscale}, volume = {13}, number = {25}, pages = {11250-11261}, doi = {10.1039/d0nr07981b}, pmid = {34152347}, issn = {2040-3372}, mesh = {Albumins ; Animals ; Cisplatin ; Fluorouracil ; *Gastrointestinal Microbiome ; Mice ; *Mucositis ; *Nanoparticles ; }, abstract = {Chemotherapy-associated intestinal mucositis is still one of the major challenges in the first-line clinical cancer treatment. Selenium element has shown health benefits on enteritis upon uptake in trace amounts; however, it was limited because of its narrow safety margin. In this work, a new form of Se@Albumin complex nanoparticles (Se@Albumin NPs) was developed by self-assembly of denatured human serum albumin and selenite salts. Se@Albumin NPs significantly improve intestinal mucositis induced with cisplatin (CDDP) in a mouse model via attenuating the level of intestinal oxidative stress, reducing intestinal permeability, and relieving gastric dysmotility. It is very interesting that the restoration of anti-inflammatory bacteria (Bacteroidetes and Firmicutes) and reduced abundance of proinflammatory bacteria (Escherichia) contributed to the reduction of intestinal mucositis by Se@Albumin NPs in mice. In addition, the fecal microbiota transplantation (FMT) with materials from Se@Albumin NP-treated mice significantly protected pseudo-aseptic mice from CDDP-induced intestinal mucositis. In conclusion, our findings showed that Se@Albumin NPs can significantly improve CDDP-induced intestinal mucositis, and its function may be directly mediated by gut microbiota regulation, which will provide new helpful information for clinical treatment.}, }
@article {pmid34151049, year = {2021}, author = {West, C and McVey Neufeld, KA}, title = {Animal models of visceral pain and the role of the microbiome.}, journal = {Neurobiology of pain (Cambridge, Mass.)}, volume = {10}, number = {}, pages = {100064}, pmid = {34151049}, issn = {2452-073X}, abstract = {Visceral pain refers to pain arising from the internal organs and is distinctly different from the expression and mechanisms of somatic pain. Diseases and disorders with increased visceral pain are associated with significantly reduced quality of life and incur large financial costs due to medical visits and lost work productivity. In spite of the notable burden of illness associated with those disorders involving increased visceral pain, and some knowledge regarding etiology, few successful therapeutics have emerged, and thus increased attention to animal models of visceral hypersensitivity is warranted in order to elucidate new treatment opportunities. Altered microbiota-gut-brain (MGB) axis communication is central to the comorbid gastrointestinal/psychiatric diseases of which increased visceral (intestinal) sensitivity is a hallmark. This has led to a particular focus on intestinal microbiome disruption and its potential role in the etiology of heightened visceral pain. Here we provide a review of studies examining models of heightened visceral pain due to altered bidirectional communication of the MGB axis, many of which are conducted on a background of stress exposure. We discuss work in which the intestinal microbiota has either been directly manipulated (as with germ-free, antibiotic, and fecal microbial transplantation studies) or indirectly affected through early life or adult stress, inflammation, and infection. Animal models of visceral pain alterations with accompanying changes to the intestinal microbiome have the highest face and construct validity to the human condition and are the focus of the current review.}, }
@article {pmid34150673, year = {2021}, author = {Varga, A and Kocsis, B and Sipos, D and Kása, P and Vigvári, S and Pál, S and Dembrovszky, F and Farkas, K and Péterfi, Z}, title = {How to Apply FMT More Effectively, Conveniently and Flexible - A Comparison of FMT Methods.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {657320}, pmid = {34150673}, issn = {2235-2988}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {PURPOSE: Metronidazol and vancomycin were long the two best options against Clostridioides (formerly Clostridium) difficile infections (CDI). Now, the cost of new drugs such as fidaxomicin directs us towards alternative treatment options, such as faecal microbiota transplant (FMT). Its effectiveness is similar to fidaxomicin. There are questions regarding its safety, but the biggest challenges are prejudice and inconvenience. Most protocols refer to FMT applied in the form of a solution. We investigated different modalities of FMT.<br><br>METHODS: Instead of using nasoenteric tubes or colonoscopy, we place frozen or lyophilised stool in non-coated, size "00", hard gelatine capsules or enterosolvent, size "0" capsules.<br><br>RESULTS: We found that non-coated, size "00", hard gelatine capsules are appropriate for conducting FMT. Capsules containing lyophilised supernatant with a low number of bacteria have been proven to be non-inferior to other FMT modalities. The primary cure rate in the supernatant group was 93.75%, and 66.67% in the sediment group. The overall cure rate was 82.14%. Depending on the protocol, 4-7 capsules are sufficient per patient. Capsules can be stored for up to one year at -20&#xb0;C.<br><br>CONCLUSIONS: FMT is a feasible alternative to antibiotic treatments in CDI. Our method makes the process flexible and less inconvenient to patients. Long storage time allows a consistent supply of capsules, while small volume and formulation make the procedure tolerable.}, }
@article {pmid34149723, year = {2021}, author = {Ponce-Alonso, M and García-Hoz, C and Halperin, A and Nuño, J and Nicolás, P and Martínez-Pérez, A and Ocaña, J and García-Pérez, JC and Guerrero, A and López-Sanromán, A and Cantón, R and Roy, G and Del Campo, R}, title = {An Immunologic Compatibility Testing Was Not Useful for Donor Selection in Fecal Microbiota Transplantation for Ulcerative Colitis.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {683387}, pmid = {34149723}, issn = {1664-3224}, mesh = {Adult ; Aged ; Clinical Decision-Making ; Colitis, Ulcerative/diagnosis/*immunology/*therapy ; Disease Management ; *Donor Selection ; *Fecal Microbiota Transplantation ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient's mucosal immune response against the donor's microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&amp;D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient's local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.}, }
@article {pmid34147969, year = {2021}, author = {Wang, S and Ishima, T and Qu, Y and Shan, J and Chang, L and Wei, Y and Zhang, J and Pu, Y and Fujita, Y and Tan, Y and Wang, X and Ma, L and Wan, X and Hammock, BD and Hashimoto, K}, title = {Ingestion of Faecalibaculum rodentium causes depression-like phenotypes in resilient Ephx2 knock-out mice: A role of brain-gut-microbiota axis via the subdiaphragmatic vagus nerve.}, journal = {Journal of affective disorders}, volume = {292}, number = {}, pages = {565-573}, pmid = {34147969}, issn = {1573-2517}, support = {P42 ES004699/ES/NIEHS NIH HHS/United States ; R35 ES030443/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Brain ; *Depression/genetics ; Eating ; Epoxide Hydrolases ; Firmicutes ; *Gastrointestinal Microbiome/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; Stress, Psychological ; Vagus Nerve ; }, abstract = {BACKGROUND: The brain-gut-microbiota axis plays a crucial role in the bidirectional interactions between the brain and the gut. Soluble epoxide hydrolase (coded by the Ephx2 gene) plays an important role in inflammation, which has been implicated in stress-related depression. Ephx2 knock-out (KO) mice exposed to chronic social defeat stress (CSDS) did not show depression-like behaviors, indicating stress resilience. Here we examined whether the brain-gut-microbiota axis influences the resilience in Ephx2 KO mice.<br><br>METHODS: Effects of fecal microbiota transplantation (FMT) from CSDS-susceptible (or control) mice in wild-type (WT) mice and Ephx2 KO mice treated with an antibiotic cocktail (ABX) were investigated. Behavioral, biochemical tests and 16S ribosome RNA analysis were performed.<br><br>RESULTS: FMT from CSDS-susceptible mice produced anhedonia-like behavior in ABX-treated WT and Ephx2 KO mice. The 16S ribosome RNA analysis showed that Faecalibaculum rodentium (F. rodentium) may be responsible for the observed anhedonia-like behavior following FMT from CSDS-susceptible mice. Ingestion of F. rodentium for 14 days produced depression- and anhedonia-like behaviors, higher blood levels of interleukin-6, and reduced expression of synaptic proteins in the prefrontal cortex of ABX-treated Ephx2 KO mice. Furthermore, subdiaphragmatic vagotomy blocked the development of these behavioral abnormalities after ingestion of F. rodentium.<br><br>LIMITATIONS: Detailed mechanisms are unclear.<br><br>CONCLUSIONS: These findings suggest that F. rodentium might contribute to the conversion of resilient Ephx2 KO mice into KO mice with depression-like phenotypes. The brain-gut-microbiota axis via the subdiaphragmatic vagus nerve plays a crucial role in susceptibility and resilience to stress.}, }
@article {pmid34145677, year = {2022}, author = {El-Salhy, M and Kristoffersen, AB and Valeur, J and Casen, C and Hatlebakk, JG and Gilja, OH and Hausken, T}, title = {Long-term effects of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome.}, journal = {Neurogastroenterology and motility}, volume = {34}, number = {1}, pages = {e14200}, doi = {10.1111/nmo.14200}, pmid = {34145677}, issn = {1365-2982}, mesh = {Adult ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/*physiology ; Humans ; Irritable Bowel Syndrome/*therapy ; Male ; Middle Aged ; *Quality of Life ; Surveys and Questionnaires ; Treatment Outcome ; }, abstract = {BACKGROUND: We recently found fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) patients to be an effective and safe treatment after 3 months. The present follow-up study investigated the efficacy and safety of FMT at 1 year after treatment.<br><br>METHODS: This study included 77 of the 91 IBS patients who had responded to FMT in our previous study. Patients provided a fecal sample and completed five questionnaires to assess their symptoms and quality of life at 1&#xa0;year after FMT. The dysbiosis index (DI) and fecal bacterial profile were analyzed using a 16S rRNA gene-based DNA probe hybridization. The levels of fecal short-chain fatty acids (SCFAs) were determined by gas chromatography.<br><br>RESULTS: There was a persistent response to FMT at 1&#xa0;year after treatment in 32 (86.5%) and 35 (87.5%) patients who received 30-g and 60-g FMT, respectively. In the 30-g FMT group, 12 (32.4%) and 8 (21.6%) patients showed complete remission at 1&#xa0;year and 3&#xa0;months, respectively; the corresponding numbers in the 60-g FMT group were 18 (45%) and 11 (27.5%), respectively. Abdominal symptoms and the quality of life were improved at 1&#xa0;year compared with after 3&#xa0;months. These findings were accompanied by comprehensive changes in the fecal bacterial profile and SCFAs.<br><br>CONCLUSIONS: Most of the IBS patients maintained a response at 1&#xa0;year after FMT. Moreover, the improvements in symptoms and quality of life increased over time. Changes in DI, fecal bacterial profile and SCFAs were more comprehensive at 1&#xa0;year than after 3&#xa0;months. www.clinicaltrials.gov (NCT03822299).}, }
@article {pmid34145455, year = {2021}, author = {Yang, YL and Zhou, WW and Wu, S and Tang, WL and Wang, ZW and Zhou, ZY and Li, ZW and Huang, QF and He, Y and Zhou, HW}, title = {Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome.}, journal = {Endocrinology}, volume = {162}, number = {10}, pages = {}, pmid = {34145455}, issn = {1945-7170}, mesh = {Animals ; Bacteroides ; Biomarkers/metabolism ; Case-Control Studies ; Chenodeoxycholic Acid/metabolism ; Female ; Fibroblast Growth Factors/metabolism ; *Gastrointestinal Microbiome ; Glucose/metabolism ; Glucose Tolerance Test ; Humans ; *Insulin Resistance ; Letrozole/pharmacology ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Phenotype ; Polycystic Ovary Syndrome/*microbiology ; RNA, Ribosomal, 16S ; Receptors, Cytoplasmic and Nuclear/metabolism ; Sequence Analysis, DNA ; }, abstract = {CONTEXT: The key gut microbial biomarkers for polycystic ovarian syndrome (PCOS) and how dysbiosis causes insulin resistance and PCOS remain unclear.<br><br>OBJECTIVE: To assess the characteristics of intestinal flora in PCOS and explore whether abnormal intestinal flora can affect insulin resistance and promote PCOS and whether chenodeoxycholic acid (CDCA) can activate intestinal farnesoid X receptor (FXR), improving glucose metabolism in PCOS.<br><br>SETTING AND DESIGN: The intestinal flora of treatment-na&#xef;ve PCOS patients and hormonally healthy controls was analyzed. Phenotype analysis, intestinal flora analysis, and global metabolomic profiling of caecal contents were performed on a letrozole-induced PCOS mouse model; similar analyses were conducted after 35 days of antibiotic treatment on the PCOS mouse model, and glucose tolerance testing was performed on the PCOS mouse model after a 35-day CDCA treatment. Mice receiving fecal microbiota transplants from PCOS patients or healthy controls were evaluated after 10 weeks.<br><br>RESULTS: Bacteroides was significantly enriched in treatment-na&#xef;ve PCOS patients. The enrichment in Bacteroides was reproduced in the PCOS mouse model. Gut microbiota removal ameliorated the PCOS phenotype and insulin resistance and increased relative FXR mRNA levels in the ileum and serum fibroblast growth factor 15 levels. PCOS stool-transplanted mice exhibited insulin resistance at 10 weeks but not PCOS. Treating the PCOS mouse model with CDCA improved glucose metabolism.<br><br>CONCLUSIONS: Bacteroides is a key microbial biomarker in PCOS and shows diagnostic value. Gut dysbiosis can cause insulin resistance. FXR activation might play a beneficial rather than detrimental role in glucose metabolism in PCOS.}, }
@article {pmid34144192, year = {2021}, author = {Tang, B and Zhu, J and Fang, S and Wang, Y and Vinothkumar, R and Li, M and Weng, Q and Zheng, L and Yang, Y and Qiu, R and Xu, M and Zhao, Z and Ji, J}, title = {Pharmacological inhibition of MELK restricts ferroptosis and the inflammatory response in colitis and colitis-propelled carcinogenesis.}, journal = {Free radical biology &amp; medicine}, volume = {172}, number = {}, pages = {312-329}, doi = {10.1016/j.freeradbiomed.2021.06.012}, pmid = {34144192}, issn = {1873-4596}, mesh = {Animals ; Carcinogenesis ; *Colitis/chemically induced/complications/drug therapy ; Dextran Sulfate ; Disease Models, Animal ; *Ferroptosis ; Humans ; Mice ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction ; }, abstract = {INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic recurrent and incurable gastrointestinal diseases with an unknown etiology that leads to a high risk of developing colitis-associated colorectal cancer (CRC).<br><br>OBJECTIVES: In this study, we measured the expression characteristics of MELK in IBD and CRC tissues and explored the regulatory effect of OTSSP167 (a MELK-selective inhibitor) on the mice models of colitis and colitis-associated carcinogenesis and analyzed the specific molecular mechanisms.<br><br>METHODS: DSS-induced colitis and colitis-associated carcinogenesis (CAC) model were treated with MELK inhibitor OTSSP167 then the fight against effect of OTSSP167 in the clinical symptoms of colitis and CAC was measured. In addition, underlying mechanism of OTSSP167 treatment in vitro and vivo including anti-ferroptosis and anti-inflammatory response effect was further explored.<br><br>RESULTS: We found that pharmacological inhibition of MELK was indicated to significantly alleviate the inflammatory response in mice with colitis, reduce intestinal damage, and effectively inhibit the occurrence and progression of colitis-propelled carcinogenesis, which was closely related to the regulation of gut microbial composition, and OTSSP167-mediated fecal microbiota transplantation effectively alleviated DSS-induced colitis. In addition, OTSSP167 treatment obviously inhibited ferroptosis in the intestinal tissue and suppressed macrophage infiltration and M1 polarization, which reduced the secretion of pro-inflammatory factors. Further exploration of the molecular mechanism revealed that OTSSP167 inhibited AKT/IKK/P65 and ERK/IKK/P65 signaling cascades both in vivo and in vitro, which may help alleviate intestinal inflammation and control the occurrence of cancer.<br><br>CONCLUSION: Our findings lay a theoretical foundation for the use of OTSSP167 as a treatment for IBD and its inhibition of the occurrence of colitis-associated carcinogenesis; additionally, MELK may be a potentially effective target molecule, thus providing more options for clinical treatment.}, }
@article {pmid34143726, year = {2021}, author = {Guittar, J and Koffel, T and Shade, A and Klausmeier, CA and Litchman, E}, title = {Resource Competition and Host Feedbacks Underlie Regime Shifts in Gut Microbiota.}, journal = {The American naturalist}, volume = {198}, number = {1}, pages = {1-12}, doi = {10.1086/714527}, pmid = {34143726}, issn = {1537-5323}, mesh = {Diet ; Dysbiosis ; Feedback ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {AbstractThe spread of an enteric pathogen in the human gut depends on many interacting factors, including pathogen exposure, diet, host gut environment, and host microbiota, but how these factors jointly influence infection outcomes remains poorly characterized. Here we develop a model of host-mediated resource competition between mutualistic and pathogenic taxa in the gut that aims to explain why similar hosts, exposed to the same pathogen, can have such different infection outcomes. Our model successfully reproduces several empirically observed phenomena related to transitions between healthy and infected states, including (1) the nonlinear relationship between pathogen inoculum size and infection persistence, (2) the elevated risk of chronic infection during or after treatment with broad-spectrum antibiotics, (3) the resolution of gut dysbiosis with fecal microbiota transplants, and (4) the potential protection from infection conferred by probiotics. We then use the model to explore how host-mediated interventions-namely, shifts in the supply rates of electron donors (e.g., dietary fiber) and respiratory electron acceptors (e.g., oxygen)-can potentially be used to direct gut community assembly. Our study demonstrates how resource competition and ecological feedbacks between the host and the gut microbiota can be critical determinants of human health outcomes. We identify several testable model predictions ready for experimental validation.}, }
@article {pmid34142885, year = {2021}, author = {Silva, CBP and Elias-Oliveira, J and McCarthy, CG and Wenceslau, CF and Carlos, D and Tostes, RC}, title = {Ethanol: striking the cardiovascular system by harming the gut microbiota.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {321}, number = {2}, pages = {H275-H291}, pmid = {34142885}, issn = {1522-1539}, support = {K99 HL151889/HL/NHLBI NIH HHS/United States ; R00GM118885//Foundation for the National Institutes of Health (FNIH)/ ; R01 HL149762/HL/NHLBI NIH HHS/United States ; R01HL149762//Foundation for the National Institutes of Health (FNIH)/ ; R00 HL151889/HL/NHLBI NIH HHS/United States ; R00 GM118885/GM/NIGMS NIH HHS/United States ; }, mesh = {Alcohol Drinking/immunology/*physiopathology ; Anti-Bacterial Agents/therapeutic use ; Anti-Infective Agents, Local ; Cardiovascular Diseases/immunology/*physiopathology/therapy ; Dysbiosis/immunology/*physiopathology/therapy ; Ethanol ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {Ethanol consumption represents a significant public health problem, and excessive ethanol intake is a risk factor for cardiovascular disease (CVD), one of the leading causes of death and disability worldwide. The mechanisms underlying the effects of ethanol on the cardiovascular system are complex and not fully comprehended. The gut microbiota and their metabolites are indispensable symbionts essential for health and homeostasis and therefore, have emerged as potential contributors to ethanol-induced cardiovascular system dysfunction. By mechanisms that are not completely understood, the gut microbiota modulates the immune system and activates several signaling pathways that stimulate inflammatory responses, which in turn, contribute to the development and progression of CVD. This review summarizes preclinical and clinical evidence on the effects of ethanol in the gut microbiota and discusses the mechanisms by which ethanol-induced gut dysbiosis leads to the activation of the immune system and cardiovascular dysfunction. The cross talk between ethanol consumption and the gut microbiota and its implications are detailed. In summary, an imbalance in the symbiotic relationship between the host and the commensal microbiota in a holobiont, as seen with ethanol consumption, may contribute to CVD. Therefore, manipulating the gut microbiota, by using antibiotics, probiotics, prebiotics, and fecal microbiota transplantation might prove a valuable opportunity to prevent/mitigate the deleterious effects of ethanol and improve cardiovascular health and risk prevention.}, }
@article {pmid34140459, year = {2021}, author = {Nicholson, MR and Hourigan, SK and Conrad, M and Goyal, A and Jensen, K and Kelsen, J and Kennedy, M and Weatherly, M and Kahn, SA}, title = {Current Challenges in Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children.}, journal = {The American journal of gastroenterology}, volume = {116}, number = {9}, pages = {1954-1956}, pmid = {34140459}, issn = {1572-0241}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; K23 DK119585/DK/NIDDK NIH HHS/United States ; K23 HD099240/HD/NICHD NIH HHS/United States ; UL1 TR000445/TR/NCATS NIH HHS/United States ; }, mesh = {*COVID-19 ; Child ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; *Practice Patterns, Physicians' ; SARS-CoV-2/*isolation &amp; purification ; Surveys and Questionnaires ; United States ; }, abstract = {INTRODUCTION: The impact of the 2019 US Food and Drug Administration safety alert involving transmission of multidrug resistant organisms through fecal microbiota transplantation (FMT), and the COVID-19 pandemic on the use of FMT in children, is unknown.<br><br>METHODS: A survey of pediatric gastroenterologists performing FMT for Clostridioides difficile infection was conducted.<br><br>RESULTS: Of 36 respondents, 17 (47%) and 30 (83%) changed their FMT practices related to the US Food and Drug Administration safety alert and COVID-19 pandemic, respectively, with 22 (61%) of programs halted.<br><br>DISCUSSION: The US Food and Drug Administration safety alert and COVID-19 pandemic have substantially influenced the availability and access of FMT for children.}, }
@article {pmid34139232, year = {2021}, author = {Chatterjee, S and Bose, D and Seth, R}, title = {Host gut microbiome and potential therapeutics in Gulf War Illness: A short review.}, journal = {Life sciences}, volume = {280}, number = {}, pages = {119717}, doi = {10.1016/j.lfs.2021.119717}, pmid = {34139232}, issn = {1879-0631}, mesh = {Animals ; Dysbiosis/microbiology/therapy/virology ; Fatty Acids, Volatile/therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Persian Gulf Syndrome/microbiology/*therapy/virology ; Phenols/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {AIMS: Since our troops had returned from the first Persian Gulf War in 1990-91, the veterans have reported chronic multisymptomatic illness widely referred to as Gulf War Illness (GWI). We aim to review the current directions of GWI pathology research in the context of chronic multisymptomatic illness and its possible gut microbiome targeted therapies. The veterans of Gulf War show symptoms of chronic fatigue, cognitive deficits, and a subsection report of gastrointestinal complications.<br><br>METHOD: Efforts of finding a suitable treatment regimen and clinical management remain a challenge. More recently, we have shown that the pathology is connected to alterations in the gut microbiome, and efforts of finding a suitable regimen for gut-directed therapeutics are underway. We discuss the various clinical interventions and summarize the possible effectiveness of gut-directed therapies such as the use of short-chain fatty acids (SCFA), phenolic compounds, and their metabolites, use of probiotics, and fecal microbiota transfer.<br><br>SIGNIFICANCE: The short review will be helpful to GWI researchers to expand their studies to the gut and find an effective treatment strategy for chronic multisymptomatic illness.}, }
@article {pmid34139173, year = {2021}, author = {Zhu, W and Romano, KA and Li, L and Buffa, JA and Sangwan, N and Prakash, P and Tittle, AN and Li, XS and Fu, X and Androjna, C and DiDonato, AJ and Brinson, K and Trapp, BD and Fischbach, MA and Rey, FE and Hajjar, AM and DiDonato, JA and Hazen, SL}, title = {Gut microbes impact stroke severity via the trimethylamine N-oxide pathway.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {7}, pages = {1199-1208.e5}, pmid = {34139173}, issn = {1934-6069}, support = {P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R01 HL150537/HL/NHLBI NIH HHS/United States ; T32 HL134622/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/*metabolism ; Choline/metabolism ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Methylamines/*metabolism ; Mice ; Mice, Inbred C57BL ; Oxides/*metabolism ; Severity of Illness Index ; Stroke/metabolism/*microbiology/pathology ; }, abstract = {Clinical studies have demonstrated associations between circulating levels of the gut-microbiota-derived metabolite trimethylamine-N-oxide (TMAO) and stroke incident risk. However, a causal role of gut microbes in stroke has not yet been demonstrated. Herein we show that gut microbes, through dietary choline and TMAO generation, directly impact cerebral infarct size and adverse outcomes following stroke. Fecal microbial transplantation from low- versus high-TMAO-producing human subjects into germ-free mice shows that both TMAO generation and stroke severity are transmissible traits. Furthermore, employing multiple murine stroke models and transplantation of defined microbial communities with genetically engineered human commensals into germ-free mice, we demonstrate that the microbial cutC gene (an enzymatic source of choline-to-TMA transformation) is sufficient to transmit TMA/TMAO production, heighten cerebral infarct size, and lead to functional impairment. We thus reveal that gut microbiota in general, specifically the metaorganismal TMAO pathway, directly contributes to stroke severity.}, }
@article {pmid34137411, year = {2021}, author = {Zhao, R and Ji, Y and Chen, X and Hu, Q and Zhao, L}, title = {Polysaccharide from Flammulina velutipes attenuates markers of metabolic syndrome by modulating the gut microbiota and lipid metabolism in high fat diet-fed mice.}, journal = {Food &amp; function}, volume = {12}, number = {15}, pages = {6964-6980}, doi = {10.1039/d1fo00534k}, pmid = {34137411}, issn = {2042-650X}, mesh = {Animals ; Diet, High-Fat ; Flammulina/*chemistry ; Gastrointestinal Microbiome/*drug effects ; Lipid Metabolism/*drug effects ; Male ; Metabolic Syndrome/*metabolism ; Mice ; Mice, Inbred C57BL ; Plant Extracts/pharmacology ; Polysaccharides/*pharmacology ; }, abstract = {Natural biological macromolecules with putative functions of gut microbiota regulation possess the advantage of improving metabolic syndrome (MS). In this research, we aimed to determine the effects of Flammulina velutipes polysaccharide (FVP) (Expt. 1) and fecal microbiota transplantation (FMT) (Expt. 2) on MS-related disorders, gut microbiota structure changes and their underlying mechanisms in a murine model fed with high-fat diet (HFD). In Expt. 1, six-week-old male C57BL/6J mice were fed with a control diet (10% calories from fat) or a high fat diet (45% calories from fat), administered with saline or FVP (0.4 mg per g b.w.) by gavage over a 12-week period. In Expt. 2, mice were fed with a HFD, administered with fecal supernatants from healthy and FVP-fed donor mice for 12 weeks simultaneously. The body mass, blood lipid levels and blood glucose homeostasis of mice were analyzed, and total RNA from mouse liver and adipose tissue were extracted by TRIzol and the lipid metabolism-related gene expressions were calculated by qRT-PCR. Gut microbiota changes were evaluated by high-throughput sequencing. Results indicated that FVP and FMT supplementations showed an attenuation effect on mouse obesity, hyperlipidemia and insulin resistance. Up-regulated expressions of Ampkα1 and Ppara were found both in FVP and FMT treatment groups. Different changes were found in the gut microbiota caused by FVP and FMT, respectively. PICRUSt analysis indicated that compared with FVP supplementation, FMT showed a significant effect on regulating lipid metabolism in HFD-fed mice. The findings from this study indicated that oral administrations of FVP or FMT could significantly attenuate MS-related obesity, hyperlipidemia and insulin resistance in HFD-fed mice, and the beneficial effects may be mediated through lipid metabolism and gut microbiota regulation in different ways. These results improve the understanding of the functional activity of FVP as prebiotics.}, }
@article {pmid34135557, year = {2021}, author = {Wen, X and Wang, HG and Zhang, MN and Zhang, MH and Wang, H and Yang, XZ}, title = {Fecal microbiota transplantation ameliorates experimental colitis via gut microbiota and T-cell modulation.}, journal = {World journal of gastroenterology}, volume = {27}, number = {21}, pages = {2834-2849}, pmid = {34135557}, issn = {2219-2840}, mesh = {Animals ; CD8-Positive T-Lymphocytes ; *Colitis/chemically induced/therapy ; *Colitis, Ulcerative/chemically induced/therapy ; Colon ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {BACKGROUND: Emerging evidence has demonstrated that fecal microbiota transplantation (FMT) has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis (UC), although the mechanism of FMT is unclear.<br><br>AIM: To evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota, through association analysis of gut microbiota with colon transcriptome in mice.<br><br>METHODS: Dextran sodium sulfate (DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage. Severity of colon inflammation was measured by body weight, disease activity index, colon length and histological score. Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing. The differentially expressed genes (DEGs) in the colon were obtained by transcriptome sequencing. The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry.<br><br>RESULTS: Compared with the DSS group, the weight loss, colon length shortening and inflammation were significantly alleviated in the FMT group. The scores of disease activity index and colon histology decreased obviously after FMT. FMT restored the balance of gut microbiota, especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter. In the transcriptomic analysis, 128 DEGs intersected after DSS treatment and FMT. Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation. In the DSS group, there was an increase in colonic T helper CD4[+] and T cytotoxic CD8[+] cells by flow cytometry. FMT selectively downregulated the ratio of colonic CD4[+] and CD8[+] T cells to maintain intestinal homeostasis. Furthermore, Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G, CCL8 and IDO1.<br><br>CONCLUSION: FMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.}, }
@article {pmid34134605, year = {2021}, author = {Zhao, J and Bai, M and Yang, X and Wang, Y and Li, R and Sun, S}, title = {Alleviation of refractory IgA nephropathy by intensive fecal microbiota transplantation: the first case reports.}, journal = {Renal failure}, volume = {43}, number = {1}, pages = {928-933}, pmid = {34134605}, issn = {1525-6049}, mesh = {Adult ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Glomerulonephritis, IGA/*therapy ; Humans ; Middle Aged ; Remission Induction ; Serum Albumin ; }, abstract = {BACKGROUND: Gut dysbiosis may be implicated in the pathogenesis of IgA nephropathy (IgAN) through immune and/or metabolite pathways. Fecal microbiota transplantation (FMT) could reestablish the micro-ecological balance in IgAN, although this has never been attempted before. We explored whether FMT could be efficacious in treating IgAN in two patients with refractory IgAN.<br><br>CASE PRESENTATION: Two Chinese female patients with IgAN failed to achieve clinical remission after receiving several rounds of immunosuppressive therapy and suffered from unbearable adverse effects due to immunosuppressants. Both patients received intensive fresh FMT conducted through transendoscopic enteral tubing (TET) regularly for 6-7&#x2009;months, and were followed up for a further 6&#x2009;months. Partial clinical remission was achieved in both patients, evidenced by a decrease in the 24-h urinary protein (24-hUP) to less than half of baseline during FMT treatment or follow-up, along with increased serum albumin (sAlb) and stable kidney function. The gut microbiota of both patients was distorted with lower biodiversity and altered composition, which was reversed following FMT. Phylum Proteobacteria decreased while genus Prevotella increased during and after FMT. The intensive fresh FMT was well-tolerated, and no severe adverse events occurred.<br><br>CONCLUSIONS: Preliminary evidence of the safety and efficacy of FMT for treating refractory IgAN may provide a new direction by which to decipher the pathogenesis of IgAN.}, }
@article {pmid34133889, year = {2022}, author = {Mehta, N and Wang, T and Friedman-Moraco, RJ and Carpentieri, C and Mehta, AK and Rouphael, N and Dhere, T and Larsen, CP and Kraft, CS and Woodworth, MH}, title = {Fecal Microbiota Transplantation Donor Screening Updates and Research Gaps for Solid Organ Transplant Recipients.}, journal = {Journal of clinical microbiology}, volume = {60}, number = {2}, pages = {e0016121}, pmid = {34133889}, issn = {1098-660X}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; K23AI144036/AI/NIAID NIH HHS/United States ; }, mesh = {Clostridioides difficile ; *Clostridium Infections/etiology/prevention &amp; control ; Donor Selection ; *Fecal Microbiota Transplantation/methods ; Humans ; *Organ Transplantation/adverse effects ; Recurrence ; *Transplant Recipients ; Treatment Outcome ; }, abstract = {In this review, we discuss stool donor screening considerations to mitigate potential risks of pathogen transmission through fecal microbiota transplant (FMT) in solid organ transplant (SOT) recipients. SOT recipients have a higher risk for Clostridioides difficile infection (CDI) and are more likely to have severe CDI. FMT has been shown to be a valuable tool in the treatment of recurrent CDI (RCDI); however, guidelines for screening for opportunistic infections transmitted through FMT are underdeveloped. We review reported adverse effects of FMT as they pertain to an immunocompromised population and discuss the current understanding and recommendations for screening found in the literature while noting gaps in research. We conclude that while FMT is being performed in the SOT population, typically with positive results, there remain many unanswered questions which may have major safety implications and warrant further study.}, }
@article {pmid34133861, year = {2021}, author = {Bajaj, JS and Kamath, PS and Reddy, KR}, title = {The Evolving Challenge of Infections in Cirrhosis.}, journal = {The New England journal of medicine}, volume = {384}, number = {24}, pages = {2317-2330}, doi = {10.1056/NEJMra2021808}, pmid = {34133861}, issn = {1533-4406}, mesh = {Algorithms ; Anti-Bacterial Agents/therapeutic use ; Bacterial Infections/diagnosis/*etiology/therapy ; Candidiasis/etiology ; Chronic Disease ; Cross Infection/etiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Hospital Mortality ; Humans ; Liver Cirrhosis/*complications/immunology/mortality ; Phage Therapy ; Risk Factors ; Sepsis/etiology ; }, }
@article {pmid34132630, year = {2021}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Nalluri, H and Kaiser, T and Holtan, SG and Khoruts, A and Weisdorf, DJ and Staley, C}, title = {Effect of COVID-19 precautions on the gut microbiota and nosocomial infections.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-10}, pmid = {34132630}, issn = {1949-0984}, support = {KL2 TR002492/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; Antineoplastic Agents/therapeutic use ; COVID-19/*prevention &amp; control ; Cross Infection/*epidemiology ; Disease Susceptibility/*microbiology ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Humans ; Length of Stay ; Leukemia, Myeloid, Acute/*drug therapy ; Masks ; Middle Aged ; Physical Distancing ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics ; Risk ; SARS-CoV-2 ; }, abstract = {COVID-19 precautions decrease social connectedness. It has been proposed that these measures alter the gut microbiota, with potential clinical consequences. We tested this hypothesis in patients with acute myeloid leukemia (AML) receiving inpatient chemotherapy, a population with extensive exposure to the nosocomial setting and at high risk for infections. Hospitalized patients with AML contributed stool samples to a biorepository protocol that was initiated before COVID-19 and continued without change through the pandemic. Patient-, disease-, and treatment-related characteristics remained the same in the two eras and the only change in clinical care was the implementation of COVID-19 precautions in March 2020. The incidence of all-cause nosocomial infections during the pandemic was lower than in the pre-COVID-19 era. Multivariable analysis revealed an imprint of COVID-19 precautions in the gut microbiota as a viable mechanistic explanation. In conclusion, COVID-19 precautions alter the gut microbiota, thereby mediating pathogen susceptibility and nosocomial infections.}, }
@article {pmid34130227, year = {2021}, author = {Wardill, HR and van der Aa, SAR and da Silva Ferreira, AR and Havinga, R and Tissing, WJE and Harmsen, HJM}, title = {Antibiotic-induced disruption of the microbiome exacerbates chemotherapy-induced diarrhoea and can be mitigated with autologous faecal microbiota transplantation.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {153}, number = {}, pages = {27-39}, doi = {10.1016/j.ejca.2021.05.015}, pmid = {34130227}, issn = {1879-0852}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Diarrhea/*chemically induced ; Fecal Microbiota Transplantation ; Humans ; Microbiota ; Rats ; }, abstract = {BACKGROUND: Chemotherapy is well documented to disrupt the gut microbiome, leading to poor treatment outcomes and a heightened risk of adverse toxicity. Although strong associations exist between its composition and gastrointestinal toxicity, its causal contribution remains unclear. Our inability to move beyond association has limited the development and implementation of microbial-based therapeutics in chemotherapy adjuncts with no clear rationale of how and when to deliver them.<br><br>METHODS/RESULTS: Here, we investigate the impact of augmenting the gut microbiome on gastrointestinal toxicity caused by the chemotherapeutic agent, methotrexate (MTX). Faecal microbiome transplantation (FMT) delivered after MTX had no appreciable impact on gastrointestinal toxicity. In contrast, disruption of the microbiome with antibiotics administered before chemotherapy exacerbated gastrointestinal toxicity, impairing mucosal recovery (P&#xa0;<&#xa0;0.0001) whilst increasing diarrhoea severity (P&#xa0;=&#xa0;0.0007) and treatment-related mortality (P&#xa0;=&#xa0;0.0045). Importantly, these detrimental effects were reversed when the microbiome was restored using autologous FMT (P&#xa0;=&#xa0;0.03), a phenomenon dictated by the uptake and subsequent expansion of Muribaculaceae.<br><br>CONCLUSIONS: These are the first data to show that clinically impactful symptoms of gastrointestinal toxicity are dictated by the microbiome&#xa0;and provide a clear rationale for how and when to target the microbiome to mitigate the acute and chronic complications caused by disruption of the gastrointestinal microenvironment. Translation of this new knowledge should focus on stabilising and strengthening the gut microbiome before chemotherapy&#xa0;and developing new microbial approaches to accelerate recovery of the mucosa. By controlling the depth and duration of mucosal injury, secondary consequences of gastrointestinal toxicity may be avoided.}, }
@article {pmid34126062, year = {2021}, author = {Nooij, S and Ducarmon, QR and Laros, JFJ and Zwittink, RD and Norman, JM and Smits, WK and Verspaget, HW and Keller, JJ and Terveer, EM and Kuijper, EJ and , }, title = {Fecal Microbiota Transplantation Influences Procarcinogenic Escherichia coli in Recipient Recurrent Clostridioides difficile Patients.}, journal = {Gastroenterology}, volume = {161}, number = {4}, pages = {1218-1228.e5}, doi = {10.1053/j.gastro.2021.06.009}, pmid = {34126062}, issn = {1528-0012}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/diagnosis/microbiology/*therapy ; Dysbiosis ; Escherichia coli/enzymology/genetics/*growth &amp; development ; Escherichia coli Proteins/genetics/metabolism ; *Fecal Microbiota Transplantation/adverse effects ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Metagenome ; Metagenomics ; Middle Aged ; Polyketide Synthases/genetics/metabolism ; Reinfection ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Patients with multiple recurrent Clostridioides difficile infection (rCDI) have a disturbed gut microbiota that can be restored by fecal microbiota transplantation (FMT). Despite extensive screening, healthy feces donors may carry bacteria in their intestinal tract that could have long-term health effects, such as potentially procarcinogenic polyketide synthase-positive (pks[+]) Escherichia coli. Here, we aim to determine whether the pks abundance and persistence of pks[+]E coli is influenced by pks status of the donor feces.<br><br>METHODS: In a cohort of 49 patients with rCDI treated with FMT and matching donor samples-the largest cohort of its kind, to our knowledge-we retrospectively screened fecal metagenomes for pks[+]E coli and compared the presence of pks in patients before and after treatment and to their respective donors.<br><br>RESULTS: The pks island was more prevalent (P&#xa0;= .026) and abundant (P < .001) in patients with rCDI (pre-FMT, 27 of 49 [55%]; median, 0.46 reads per kilobase per million [RPKM] pks) than in healthy donors (3 of 8 donors [37.5%], 11 of 38 samples [29%]; median, 0.01 RPKM pks). The pks status of patients post-FMT depended on the pks status of the donor suspension with which the patient was treated (P&#xa0;= .046). Particularly, persistence (8 of 9 cases) or clearance (13 of 18) of pks[+]E coli in pks[+] patients was correlated to pks in the donor (P&#xa0;= .004).<br><br>CONCLUSIONS: We conclude that FMT contributes to pks[+]E coli persistence or eradication in patients with rCDI but that donor-to-patient transmission of pks[+]E coli is unlikely.}, }
@article {pmid34121091, year = {2022}, author = {Alhawaj, AF}, title = {Stem cell-based therapy for hirschsprung disease, do we have the guts to treat?.}, journal = {Gene therapy}, volume = {29}, number = {10-11}, pages = {578-587}, pmid = {34121091}, issn = {1476-5462}, mesh = {Humans ; *Hirschsprung Disease/genetics/therapy ; *Enteric Nervous System ; Stem Cell Transplantation ; Cell Differentiation ; }, abstract = {Hirschsprung disease (HSCR) is a congenital anomaly of the colon that results from failure of enteric nervous system formation, leading to a constricted dysfunctional segment of the colon with variable lengths, and necessitating surgical intervention. The underlying pathophysiology includes a defect in neural crest cells migration, proliferation and differentiation, which are partially explained by identified genetic and epigenetic alterations. Despite the high success rate of the curative surgeries, they are associated with significant adverse outcomes such as enterocolitis, fecal soiling, and chronic constipation. In addition, some patients suffer from extensive lethal variants of the disease, all of which justify the need for an alternative cure. During the last 5 years, there has been considerable progress in HSCR stem cell-based therapy research. However, many major issues remain unsolved. This review will provide concise background information on HSCR, outline the future approaches of stem cell-based HSCR therapy, review recent key publications, discuss technical and ethical challenges the field faces prior to clinical translation, and tackle such challenges by proposing solutions and evaluating existing approaches to progress further.}, }
@article {pmid34120835, year = {2021}, author = {Biruete, A and Cross, TL and Allen, JM and Kistler, BM and de Loor, H and Evenepoel, P and Fahey, GC and Bauer, L and Swanson, KS and Wilund, KR}, title = {Effect of Dietary Inulin Supplementation on the Gut Microbiota Composition and Derived Metabolites of Individuals Undergoing Hemodialysis: A Pilot Study.}, journal = {Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation}, volume = {31}, number = {5}, pages = {512-522}, pmid = {34120835}, issn = {1532-8503}, support = {T32 DK120524/DK/NIDDK NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; }, mesh = {Cross-Over Studies ; Female ; *Gastrointestinal Microbiome ; Humans ; *Inulin ; Male ; Pilot Projects ; Prebiotics ; Renal Dialysis ; Uremic Toxins ; }, abstract = {OBJECTIVE: The prebiotic fiber inulin has been studied in individuals undergoing hemodialysis (HD) due to its ability to reduce gut microbiota-derived uremic toxins. However, studies examining the effects of inulin on the gut microbiota and derived metabolites are limited in these patients. We aimed to assess the impact of a 4-week supplementation of inulin on the gut microbiota composition and microbial metabolites of patients on HD.<br><br>DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled, crossover study, twelve HD patients (55&#xa0;&#xb1;&#xa0;10&#xa0;y, 50% male, 58% Black American, BMI 31.6&#xa0;&#xb1;&#xa0;8.9&#xa0;kg/m[2], 33% diabetes mellitus) were randomized to consume inulin [10&#xa0;g/d for females; 15&#xa0;g/d for males] or maltodextrin [6&#xa0;g/d for females; 9&#xa0;g/d for males] for 4&#xa0;weeks, with a 4-week washout period. We assessed the fecal microbiota composition, fecal metabolites (short-chain fatty acids (SCFA), phenols, and indoles), and plasma indoxyl sulfate and p-cresyl sulfate.<br><br>RESULTS: At baseline, factors that explained the gut microbiota variability included BMI category and type of phosphate binder prescribed. Inulin increased the relative abundance of the phylum Verrucomicrobia and its genus Akkermansia (P interaction&#xa0;=&#xa0;0.045). Inulin and maltodextrin resulted in an increased relative abundance of the phylum Bacteroidetes and its genus Bacteroides (P&#xa0;time&#xa0;=&#xa0;0.04 and 0.03, respectively). Both treatments increased the fecal acetate and propionate (P time&#xa0;=&#xa0;0.032 and 0.027, respectively), and there was a trend toward increased fecal butyrate (P time&#xa0;=&#xa0;0.06). Inulin did not reduce fecal p-cresol or indoles, or plasma concentrations of&#xa0;p-cresyl&#xa0;sulfate or indoxyl sulfate.<br><br>CONCLUSIONS: A 4-week supplementation of inulin did not lead to major shifts in the fecal microbiota and gut microbiota-derived metabolites. This may be due to high variability among participants and an unexpected increase in fecal excretion of SCFA with maltodextrin. Larger studies are needed to determine the effects of prebiotic fibers on the gut microbiota and clinical outcomes to justify their use in patients on HD.}, }
@article {pmid34118466, year = {2022}, author = {Yeh, YM and Cheng, HT and Le, PH and Chen, CC and Kuo, CJ and Chen, CL and Chiu, CT and Chiu, CH}, title = {Implementation of fecal microbiota transplantation in a medical center for recurrent or refractory Clostridioides difficile infection and report of preliminary outcome.}, journal = {Biomedical journal}, volume = {45}, number = {3}, pages = {504-511}, pmid = {34118466}, issn = {2320-2890}, mesh = {*Clostridioides difficile ; *Clostridium Infections/drug therapy ; Fecal Microbiota Transplantation/methods ; Hospitals ; Humans ; RNA, Ribosomal, 16S ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to highly effective in the treatment of recurrent or refractory Clostridioides difficile infection (rCDI) in many countries of the world. Not until 2018, Ministry of Health and Welfare, Taiwan approved the application of FMT for rCDI under a special law. The study reported the first implementation of the technology in the medical center in Taiwan and the preliminary outcome.<br><br>METHODS: FMT was used to treat patients with rCDI in Chang Gung Memorial Hospital. FMT was delivered by gastroenterologists using colonoscope. Strict donor screening was performed according to the guidelines. We followed up the clinical course of patients after FMT. 16S rRNA sequencing of fecal samples for donor, and also recipient before and after FMT was carried out.<br><br>RESULTS: From September 2018 to June 2020, 39 patients with rCDI received FMT, with a successful rate of 89.7%. Two patients died due to causes unrelated to FMT, and two other cases showed no clinical improvement after the procedure. High school and college students showed the best pass rate during donor screening. The presence of multi-drug resistant pathogen was the most common cause for screening failure. We demonstrated in a case the use of rRNA sequencing as a biomarker indicating for the improvement of dysbiosis in a patient after FMT.<br><br>CONCLUSIONS: FMT was successfully implemented in a medical center in Taiwan and showed a comparable successful rate in treating rCDI, compared to other countries. Safety remains the most important issue when applying FMT in the clinical setting.}, }
@article {pmid34118462, year = {2022}, author = {Li, Y and Cao, W and Gao, NL and Zhao, XM and Chen, WH}, title = {Consistent Alterations of Human Fecal Microbes After Transplantation into Germ-free Mice.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {20}, number = {2}, pages = {382-393}, pmid = {34118462}, issn = {2210-3244}, mesh = {Humans ; Animals ; *Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Disease Models, Animal ; }, abstract = {Fecal microbiota transplantation (FMT) of human fecal samples into germ-free (GF) mice is useful for establishing causal relationships between the gut microbiota and human phenotypes. However, due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms, it may not be possible to replicate human phenotypes in mice through FMT; similarly, treatments that are effective in mouse models may not be effective in humans. In this study, we aimed to identify human gut microbes that undergo significant and consistent changes (i.e., in relative abundances) after transplantation into GF mice in multiple experimental settings. We collected 16S rDNA-seq data from four published studies and analyzed the gut microbiota profiles from 1713 human-mouse pairs. Strikingly, on average, we found that only 47% of the human gut microbes could be re-established in mice at the species level, among which more than 1/3 underwent significant changes (referred to as "variable taxa"). Most of the human gut microbes that underwent significant changes were consistent across multiple human-mouse pairs and experimental settings. Consequently, about 1/3 of human samples changed their enterotypes, i.e., significant changes in their leading species after FMT. Mice fed with a controlled diet showed a lower enterotype change rate (23.5%) than those fed with a noncontrolled diet (49.0%), suggesting a possible solution for rescue. Most of the variable taxa have been reported to be implicated in human diseases, with some recognized as the causative species. Our results highlight the challenges of using a mouse model to replicate human gut microbiota-associated phenotypes, provide useful information for researchers using mice in gut microbiota studies, and call for additional validations after FMT. An online database named FMT-DB is publicly available at http://fmt2mice.humangut.info/#/.}, }
@article {pmid34118455, year = {2021}, author = {Katz-Agranov, N and Zandman-Goddard, G}, title = {Autoimmunity and COVID-19 - The microbiotal connection.}, journal = {Autoimmunity reviews}, volume = {20}, number = {8}, pages = {102865}, pmid = {34118455}, issn = {1873-0183}, mesh = {Autoimmunity ; *COVID-19 ; Dysbiosis ; Humans ; Pandemics ; SARS-CoV-2 ; }, abstract = {BACKGROUND AND AIMS: The novel SARS-CoV-2 has been rattling the world since its outbreak in December 2019, leading to the COVID-19 pandemic. The learning curve of this new virus has been steep, with a global scientific community desperate to learn how the virus is transmitted, how it replicates, why it causes such a wide spectrum of disease manifestations, resulting in none or few symptoms in some. Others are burdened by an intense immune response that resembles the cytokine storm syndrome (CSS), which leads to severe disease manifestations, often complicated by fatal acute respiratory distress syndrome and death. Research efforts have been focusing on finding effective cures and vaccinations for this virus. The presence of SARS-CoV-2 in the gastrointestinal (GI) tract, represented by several GI manifestations, has led to its investigation as a target for the virus and as an indicator of disease severity. The response of the microbiome (which is heavily linked to immunity) to the novel SARS-CoV-2 virus, and its role in igniting the exaggerated immune response has therefore become a focus of interest. The objective of our study was to gather the data connecting between the microbiome, the GI tract and COVID-19 and to investigate whether these reported alterations in the gut microbiome bear any resemblance to those seen in lupus, the prototypical autoimmune disease. Confirming such changes may become the steppingstone to potential therapies that may prevent transmission, progression and immune related manifestations of COVID-19, via manipulation of the gut microbiota.<br><br>METHODS: We performed an extensive literature review, utilizing the Pubmed search engine and Google Scholar for studies evaluating the microbiome in COVID-19 patients and compared results with studies evaluating the microbiome in lupus. We searched for the terms: microbiome, dysbiosis, COVID-19, SARS-CoV-2, gastrointestinal as well as lupus and autoimmune. While there were hundreds of articles which referred to gastrointestinal manifestations in COVID-19, to date only 4 studies investigated the gastrointestinal microbiome in this setting. We compared the similarities between microbiome of COVID-19 patients and lupus patients.<br><br>RESULTS: We found that there are several similar processes of immune dysregulation in patients with COVID-19 and in those with lupus, with several other alterations seen in other pathological states. Some of these similarities include loss of microbiota biodiversity, increased representation of pathobionts, which are microbes associated with inflammation and disease (i.e Proteobacteria) and a relative decrease of symbionts, which are protective microbes, associated with anti-inflammatory properties (i.e Lactobacillus). Compromise to the intestinal barrier has also been reported in both.<br><br>CONCLUSIONS: We conclude that the gastrointestinal tract contributes to the disease manifestations in COVID-19. Whether gastrointestinal dysbiosis is the cause or effect of gastrointestinal manifestations and several severe systemic manifestations, which may be the response to an increased pro-inflammatory environment, is still debatable and warrants further investigation. Given the resemblance of the microbiome in COVID-19 patients to that seen in lupus patients, it becomes clearer why several therapies used in autoimmune conditions are currently under investigation for the treatment of COVID-19 patients. Moreover, these findings should promote further investigating the utility of manipulation of the microbiome, via nutritional supplementation or even fecal transplantations, interventions that may alter the course of the disease, and potentially prevent disease transmission at low cost and low risk.}, }
@article {pmid34118321, year = {2022}, author = {Núñez F, P and Quera, R and Bay, C and Thomson, P}, title = {Fecal microbiota transplant, its usefulness beyond Clostridioides difficile in gastrointestinal diseases.}, journal = {Gastroenterologia y hepatologia}, volume = {45}, number = {3}, pages = {223-230}, doi = {10.1016/j.gastrohep.2021.05.009}, pmid = {34118321}, issn = {0210-5705}, mesh = {Cholangitis, Sclerosing/therapy ; Clostridioides difficile ; Dysbiosis/therapy ; Enterocolitis, Pseudomembranous/therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Diseases/*therapy ; Gastrointestinal Microbiome ; Hepatic Encephalopathy/therapy ; Hepatitis, Alcoholic/therapy ; Humans ; Inflammatory Bowel Diseases/therapy ; Irritable Bowel Syndrome/therapy ; Non-alcoholic Fatty Liver Disease/therapy ; Recurrence ; }, abstract = {Fecal microbiota transplant (FMT) is currently recommended for recurrent Clostridioidesdifficile infection. However, it is interesting to acknowledge the potential therapeutic role in other diseases associated with dysbiosis. This review will focus on the current and potential indications of FMT in gastrointestinal diseases, evaluating the available evidence and also exposing the necessary requirements to carry it out.}, }
@article {pmid34117599, year = {2021}, author = {Inoue, M and Shishida, M and Watanabe, A and Kajikawa, R and Kajiwara, R and Sawada, H and Ohmori, I and Miyamoto, K and Ikeda, M and Toyota, K and Sadamoto, S and Takahashi, T}, title = {A liver metastasis 7 years after resection of a low-risk duodenal gastrointestinal stromal tumor.}, journal = {Clinical journal of gastroenterology}, volume = {14}, number = {5}, pages = {1464-1469}, pmid = {34117599}, issn = {1865-7265}, mesh = {*Duodenal Neoplasms/diagnostic imaging/surgery ; Duodenum ; Female ; *Gastrointestinal Stromal Tumors/diagnostic imaging/surgery ; Humans ; Imatinib Mesylate/therapeutic use ; *Liver Neoplasms/diagnostic imaging/surgery ; Middle Aged ; }, abstract = {Duodenal gastrointestinal stromal tumors (dGISTs) are rare, and a lack of consensus exists regarding their treatment, particularly for recurrent disease. We herein report a rare case of liver metastasis 7 years after resection of a low-risk duodenal gastrointestinal stromal tumor. A 45-year-old woman revealed positive fecal occult blood. Upper gastrointestinal endoscopy revealed a submucosal duodenal tumor with ulceration and oozing on the apex. Endoscopic ultrasound showed a hypoechoic mass originating in the submucosa. Contrast-enhanced abdominal computed tomography (CT) revealed a 30-mm hyper-vascular tumor in the duodenal bulb. The patient underwent partial resection of the duodenal bulb with distal gastrectomy, followed by Roux-en-Y reconstruction. Histopathological evaluation revealed a tumor comprised of spindle-shaped cells including 5 mitotic figures per 50 high-power fields. Immunohistochemical evaluation indicated that the tumor cells were positive for c-Kit and CD34 expression. The tumor was diagnosed as low-risk dGIST. Postoperative follow-up was continued, and 7 years later, CT revealed a 39-mm enhanced tumor in liver segment 4. The tumor was diagnosed as a metastatic liver tumor, and the patient underwent S4 partial hepatectomy. As a result of histological and immunohistochemical analysis, the tumor was diagnosed as a liver metastasis from dGIST. The patient has been receiving oral imatinib 400 mg daily and remains free of disease 5 years after her last surgery. Low-risk dGIST can metastasize relatively long after surgery. However, an excellent long-term prognosis may be achieved by combining complete resection and imatinib therapy in patients with recurrent liver metastases.}, }
@article {pmid34116562, year = {2021}, author = {Wu, Y and Chen, Y and Li, Q and Ye, X and Guo, X and Sun, L and Zou, J and Shen, Y and Mao, Y and Li, C and Yang, Y}, title = {Tetrahydrocurcumin alleviates allergic airway inflammation in asthmatic mice by modulating the gut microbiota.}, journal = {Food &amp; function}, volume = {12}, number = {15}, pages = {6830-6840}, doi = {10.1039/d1fo00194a}, pmid = {34116562}, issn = {2042-650X}, mesh = {Animals ; *Asthma/metabolism/microbiology/pathology ; Curcumin/*analogs &amp; derivatives/pharmacology ; Female ; Gastrointestinal Microbiome/*drug effects ; Inflammation/pathology ; Lung/pathology ; Mice ; Mice, Inbred BALB C ; }, abstract = {Dietary factors can reshape the gut microbiota and consequently affect disease progression. We previously reported that tetrahydrocurcumin (THC), the major active metabolite of curcumin (Cur), could ameliorate allergic inflammation in asthmatic mice. Herein, we aimed to investigate whether THC or Cur exerts anti-inflammatory effects on allergic asthma via modulating gut microbiota. Ovalbumin (OVA)-induced asthmatic mice were treated with Cur or THC, and the gut microbiota profiles were analyzed by 16S rRNA sequencing. Fecal microbiota transplantation (FMT) from Cur- or THC-fed donor mice was administered to OVA-induced asthmatic mice. Nasal symptoms and inflammation patterns of lungs and colons were evaluated in control, OVA-induced and Cur-or THC-treated mice. Both Cur and THC treatment could alter the compositions of the gut microbiota in asthmatic mice, characterized by a significant decrease in the ratio of Firmicutes to Bacteroidetes; Cur or THC supplementation also reduced the relative abundances of pro-inflammatory bacteria, e.g., Proteobacteria, Intestinimonas, Unidentified-Ruminococcaceae, and Lachnospiraceae, in OVA-induced mice. The relative abundances of Unidentified-Ruminococcaceae, Romboutsia, Intestinimonas, Akkermansia, and Mucispirillum were positively associated with the levels of Th2-related factors in asthmatic mice upon Cur or THC treatment. Moreover, THC-FMT showed better preventive effects than Cur-FMT on the development of allergic inflammation in OVA-induced mice, resulting in a reduction in symptoms and Th2-mediated inflammation in both lung and colon tissues. The results reveal that Cur- or THC-mediated alleviation of airway allergic inflammation is dependent on gut microbiota modulation. THC-induced gut microbiota may have therapeutic potential for asthma treatment.}, }
@article {pmid34116209, year = {2021}, author = {Beckmann, L and Künstner, A and Freschi, ML and Huber, G and Stölting, I and Ibrahim, SM and Hirose, M and Freitag, M and Langan, EA and Matschl, U and Galuska, CE and Fuchs, B and Knobloch, JK and Busch, H and Raasch, W}, title = {Telmisartan induces a specific gut microbiota signature which may mediate its antiobesity effect.}, journal = {Pharmacological research}, volume = {170}, number = {}, pages = {105724}, doi = {10.1016/j.phrs.2021.105724}, pmid = {34116209}, issn = {1096-1186}, mesh = {Angiotensin II Type 1 Receptor Blockers/*pharmacology ; Animals ; Anti-Obesity Agents/*pharmacology ; Bacteria/*drug effects/growth &amp; development ; Diet/adverse effects ; Disease Models, Animal ; Dysbiosis ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Mice ; Obesity/*drug therapy/etiology/microbiology/physiopathology ; Rats ; Rats, Sprague-Dawley ; Telmisartan/*pharmacology ; Weight Gain/*drug effects ; }, abstract = {Telmisartan prevents diet-induced obesity (DIO) in rodents. Given that the precise underlying mechanism is not known, we examined whether a gut-related mechanism might be involved. Sprague-Dawley rats received cafeteria diet (CD) for 3 months to develop DIO and were administered either telmisartan (8 mg/kgbw) or vehicle. In addition, pair-fed (PF) rats received CD adjusted to TEL and control rats (CON) only received chow. Stool samples were analysed by 16 S rRNA gene amplicon sequencing. CD-fed rats became obese while TEL, PF and CON rats remained lean. Alpha diversity analyses indicated that bacterial diversity was similar before the study but changed over time. Beta diversity revealed a time-, CD- and telmisartan-dependent effect. The Firmicutes/Bacteroidetes ratio and the abundance of Blautia, Allobaculum and Parasutterella were higher in DIO and PF than in CON, but not in TEL. Enterotype (ET)-like clustering analyses, Kleinberg's hub network scoring and random forest analyses also indicated that telmisartan induced a specific signature of gut microbiota. In response to stool transfer from telmisartan-pre-treated donor to high-fat fed acceptor mice, body weight gain was slightly attenuated. We attribute the anti-obesity action of telmisartan treatment to diet-independent alterations in gut microbiota as the microbiota from telmisartan-treated, CD-fed rats clearly differed from those of DIO and PF rats. ET-like clustering network, random forest classification and the higher stability in bacterial co-occurrence network analyses indicate that there is more than one indicator species for telmisartan's specific signature, which is further strengthened by the fact that we cannot identify a single indicator species.}, }
@article {pmid34111616, year = {2021}, author = {Shao, S and Jia, R and Zhao, L and Zhang, Y and Guan, Y and Wen, H and Liu, J and Zhao, Y and Feng, Y and Zhang, Z and Ji, Q and Li, Q and Wang, Y}, title = {Xiao-Chai-Hu-Tang ameliorates tumor growth in cancer comorbid depressive symptoms via modulating gut microbiota-mediated TLR4/MyD88/NF-κB signaling pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {88}, number = {}, pages = {153606}, doi = {10.1016/j.phymed.2021.153606}, pmid = {34111616}, issn = {1618-095X}, mesh = {Animals ; Antidepressive Agents/pharmacology ; Antineoplastic Agents/*pharmacology ; Colorectal Neoplasms/*drug therapy/metabolism/pathology ; Comorbidity ; Depression/drug therapy/epidemiology/*pathology ; Drugs, Chinese Herbal/*pharmacology ; Dysbiosis/drug therapy/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Male ; Mice, Inbred C57BL ; Middle Aged ; Myeloid Differentiation Factor 88/metabolism ; NF-kappa B/metabolism ; Toll-Like Receptor 4/metabolism ; Xenograft Model Antitumor Assays ; Mice ; }, abstract = {BACKGROUND: Depressive symptoms are thought to promote cancer development and depressive remission has been reported to be effective for defeating cancer. The herbal formula Xiao-Chai-Hu-Tang (XCHT), that has an anti-depressive efficacy, has been widely utilized in China. However, its anti-cancer effect and underlying mechanisms remain unclear.<br><br>PURPOSE: The present study aims to investigate the effects of XCHT on the depression-associated tumor and its potential mechanisms.<br><br>METHODS: A placebo-controlled trial was conducted in cancer patients comorbid with depressive symptoms to evaluate the effects of XCHT on depressive scales, tumor-related immune indicators, and gut microbial composition. A xenografted colorectal cancer (CRC) mouse model exposure to chronic restraint stress (CRS) was established to examine XCHT effects on tumorigenesis in vivo. Further, by manipulating gut bacteria with fecal microbial transplantation (FMT) or antibiotics-induced bacterial elimination in CRS-associated xenografted model, gut microbiota-mediated anti-tumor mechanism was explored.<br><br>RESULTS: In cancer patients comorbid with depressive symptoms, XCHT showed substantial effects on improvement of depressive scales, system inflammatory levels and gut dysbiosis. In vivo, XCHT inhibited tumor growth and prolonged survival time in addition to showing anti-depressive effect. Similarly, in our clinical trial, XCHT partially reversed gut dysbiosis, particularly through reducing abundances of Parabacteroides, Blautia and Ruminococcaceae bacterium. Manipulation of gut bacteria in CRS-associated xenografted model further proved that the inhibition of XCHT on tumor progression was mediated by gut microbiota and that the underlying mechanism involves in downregulation of TLR4/MyD88/NF-&#x3ba;B signaling.<br><br>CONCLUSIONS: We demonstrated that gut microbiota mediates the anti-tumor action of the formula XCHT in cancer patients and models that were comorbid with depressive symptoms. This study implies a novel clinical significance of anti-depressive herbal medicine in the cancer treatment and clarifies the important role of gut microbiota in treating cancer accompanied by depressive symptoms.}, }
@article {pmid34111528, year = {2021}, author = {Wang, M and Cao, J and Gong, C and Amakye, WK and Yao, M and Ren, J}, title = {Exploring the microbiota-Alzheimer's disease linkage using short-term antibiotic treatment followed by fecal microbiota transplantation.}, journal = {Brain, behavior, and immunity}, volume = {96}, number = {}, pages = {227-238}, doi = {10.1016/j.bbi.2021.06.003}, pmid = {34111528}, issn = {1090-2139}, mesh = {*Alzheimer Disease/therapy ; Amyloid beta-Peptides ; Animals ; Anti-Bacterial Agents ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Mice ; Mice, Transgenic ; *Microbiota ; }, abstract = {Gut microbiota is proven to be involved in the development of beta amyloid (Aβ) pathology in Alzheimer's disease (AD). Since there are difficulties in translating microbiota findings based on germ-free mice into clinical practice, here, we used short-term antibiotic cocktail treatment to develop a novel model with a near-germ-free status and without impacting Aβ pathology. Three months old APPSWE/PS1ΔE9 mice were fed with antibiotic cocktails for two weeks by gavage to obtain a near "germ-free" status, and then received the donor fecal matter from the 16 months old APPSWE/PS1ΔE9 mice for 7 consecutive days. Fecal pellets were collected prior to antibiotics treatment, following antibiotic exposure, prior to and following fecal microbiota transplantation for gut microbiota analysis. Also, Aβ pathology, astrocyte and microglia morphology were further explored. Pre-antibiotic-treated mice successfully allowed engraftment of gut microbiota following 7 consecutive days gavage with aged APPSWE/PS1ΔE9 mice microbiota. Microbiota reconstitution by transplantation was largely attributable to the donor source (e.g. g_Coriobacteriaceae and g_Clostridium) and led to a significant increase in Aβ plaques. Surprisingly, astrocyte activation around Aβ plaques was suppressed rather than microglia, the well-recognized plaque phagocytic cell type in Aβ clearance, following microbiota engraftment. Our findings provide a novel framework for understanding the mechanisms of AD through the gut-brain axis and the translation of gut microbiota manipulation from bench to clinical practice.}, }
@article {pmid34108292, year = {2021}, author = {Seo, HS and Chin, HS and Kim, YH and Moon, HS and Kim, K and Nguyen, LP and Yong, D}, title = {Laboratory Aspects of Donor Screening for Fecal Microbiota Transplantation at a Korean Fecal Microbiota Bank.}, journal = {Annals of laboratory medicine}, volume = {41}, number = {6}, pages = {612}, doi = {10.3343/alm.2021.41.6.612}, pmid = {34108292}, issn = {2234-3814}, }
@article {pmid34106090, year = {2021}, author = {Babiker, A and Ingersoll, JM and Adelman, MW and Webster, AS and Broder, KJ and Stittleburg, V and Waggoner, JJ and Kraft, CS and Woodworth, MH}, title = {Validation of High-Sensitivity Severe Acute Respiratory Syndrome Coronavirus 2 Testing for Stool-Toward the New Normal for Fecal Microbiota Transplantation.}, journal = {Clinical and translational gastroenterology}, volume = {12}, number = {6}, pages = {e00363}, pmid = {34106090}, issn = {2155-384X}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; P30 AI050409/AI/NIAID NIH HHS/United States ; }, mesh = {COVID-19/diagnosis/epidemiology/*transmission/virology ; COVID-19 Testing/*methods/statistics &amp; numerical data ; Centers for Disease Control and Prevention, U.S./standards ; Fecal Microbiota Transplantation/*methods/statistics &amp; numerical data ; Feces/*virology ; Humans ; Nasopharynx/virology ; RNA, Viral/genetics ; Reverse Transcriptase Polymerase Chain Reaction/methods ; SARS-CoV-2/*genetics/isolation &amp; purification ; Tissue Donors/supply &amp; distribution ; United States ; }, abstract = {INTRODUCTION: Mounting evidence demonstrates potential for fecal-oral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US Food and Drug Administration now requires SARS-CoV-2 testing of potential feces donors before the use of stool manufactured for fecal microbiota transplantation. We sought to develop and validate a high-sensitivity SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) procedure for testing stool specimens.<br><br>METHODS: A modified extraction method was used with an RT-PCR assay adapted from the Centers for Disease Control and Prevention PCR protocol for respiratory specimens. Contrived specimens were created using pre-COVID-19 banked stool specimens and spiking in known concentrations of SARS-CoV-2-specific nucleic acid. The highest transcript concentration at which 2/2 or 1/2 SARS-CoV-2 targets were detected in 9/10 replicates was defined as the dual-target limit and single-target limit of detection, respectively. The clinical performance of the assay was evaluated with stool samples collected from 17 nasopharyngeal swab RT-PCR-positive patients and 14 nasopharyngeal RT-PCR-negative patients.<br><br>RESULTS: The dual-target and single-target limit of detection were 56 copies/&#x3bc;L and 3 copies/&#x3bc;L, respectively. SARS-CoV-2 was detected at concentrations as low as 0.6 copies/&#x3bc;L. Clinical stool samples from known COVID-19-positive patients demonstrated the detection of SARS-CoV-2 in stool up to 29 days from symptom onset with a high agreement with nasopharyngeal swab tests (kappa statistic of 0.95, P value < 0.001).<br><br>DISCUSSION: The described RT-PCR test is a sensitive and flexible approach for the detection of SARS-CoV-2 in stool specimens. We propose an integrated screening approach that incorporates this stool test to support continuation of fecal microbiota transplantation programs.}, }
@article {pmid34105758, year = {2021}, author = {Chmel, R and Pastor, Z and Novackova, M and Chmel, R}, title = {Robot-assisted donor hysterectomy in uterus transplantation - a modality to increase reproducibility.}, journal = {Ginekologia polska}, volume = {92}, number = {7}, pages = {528-531}, doi = {10.5603/GP.a2021.0052}, pmid = {34105758}, issn = {2543-6767}, mesh = {Female ; Humans ; Hysterectomy/methods ; Pelvis ; Reproducibility of Results ; *Robotic Surgical Procedures/methods ; *Robotics ; Uterus/transplantation ; }, abstract = {Uterus transplantation is a non-lifesaving vascularized composite allotransplantation procedure requiring immunosuppression until removal of the graft. The focus of uterus transplantation is changing regarding refining individual treatment procedures included in this complex treatment of absolute uterine factor infertility, such as robot-assisted donor hysterectomy. The inferior hypogastric nerve plexus should be preserved during robotic dissection of the ureter and uterine vessels to prevent postoperative complications such as urine and fecal evacuation disturbances and sexual disorders. As most uterus transplantations have been performed in living donor concepts, robot-assisted donor hysterectomy should contribute to increased availability of uterus transplantation, particularly because it uses the precise blood-less technique of surgical dissection in the deep pelvis and has cosmetic benefits among living donors.}, }
@article {pmid34104214, year = {2021}, author = {Gupta, A and Ananthakrishnan, AN}, title = {Economic burden and cost-effectiveness of therapies for Clostridiodes difficile infection: a narrative review.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211018654}, pmid = {34104214}, issn = {1756-283X}, abstract = {Clostridioides difficile is the most common cause of healthcare-associated diarrhea. Disease complications as well as recurrent infections contribute significantly to morbidity and mortality. Over the past decades, there has been a rapid increase in the incidence of C. difficile infection (CDI), with a rise in the number of community-acquired cases. CDI has a profound economic impact on both the healthcare system and patients, secondary to recurrences, hospitalization, prolonged length of stay, cost of treatment, and indirect societal costs. With emergence of newer treatment options, the standard of care is shifting from metronidazole and vancomycin towards fidaxomicin and fecal microbiota transplantation (FMT), which despite being more expensive, are more efficacious in preventing recurrences and hence overall are more beneficial forms of therapy per cost-effectiveness analyses. Data regarding preferred route of FMT, timing of FMT, and non-conventional therapies such as bezlotoxumab is scant. There is a need for further studies to elucidate the true attributable costs of CDI as well as continued cost-effectiveness research to reduce the economic burden associated with the disease and improve clinical practice.}, }
@article {pmid34104212, year = {2021}, author = {Mullish, BH and Allegretti, JR}, title = {The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211017725}, pmid = {34104212}, issn = {1756-283X}, abstract = {Clostridioides difficile infection (CDI) remains a major global cause of gastrointestinal infection, with significant associated morbidity, mortality and impact upon healthcare system resources. Recent antibiotic use is a key risk factor for the condition, with the marked antibiotic-mediated perturbations in gut microbiome diversity and composition that underpin the pathogenesis of CDI being well-recognised. However, only relatively recently has further insight been gained into the specific mechanistic links between these gut microbiome changes and CDI, with alteration of gut microbial metabolites - in particular, bile acid metabolism - being a particular area of focus. A variety of in vitro, ex vivo, animal model and human studies have now demonstrated that loss of gut microbiome members with bile-metabolising capacity (including bile salt hydrolases, and 7-α-dehydroxylase) - with a resulting alteration of the gut bile acid milieu - contributes significantly to the disease process in CDI. More specifically, this microbiome disruption results in the enrichment of primary conjugated bile acids (including taurocholic acid, which promotes the germination of C. difficile spores) and loss of secondary bile acids (which inhibit the growth of C. difficile, and may bind to and limit activity of toxins produced by C. difficile). These bile acid changes are also associated with reduced activity of the farnesoid X receptor pathway, which may exacerbate C. difficile colitis throughout its impact upon gut barrier function and host immune/inflammatory response. Furthermore, a key mechanism of efficacy of faecal microbiota transplant (FMT) in treating recurrent CDI has been shown to be restoration of gut microbiome bile metabolising functionality; ensuring the presence of this functionality among defined microbial communities (and other 'next generation' FMT products) designed to treat CDI may be critical to their success.}, }
@article {pmid34103289, year = {2021}, author = {Heydari, A and Hatam, G and Fouladvand, M and Sadjjadi, SM and Barazesh, A}, title = {Investigating the Prevalence of Intestinal Parasites in Immunocompromised Patients in Bushehr Province, Southwest Iran: A Conventional and Molecular Study.}, journal = {Turkiye parazitolojii dergisi}, volume = {45}, number = {2}, pages = {121-127}, doi = {10.4274/tpd.galenos.2021.7145}, pmid = {34103289}, issn = {2146-3077}, mesh = {Adolescent ; Adult ; Animals ; Child ; Coccidia/classification/cytology/genetics/isolation &amp; purification ; Coccidiosis/epidemiology/immunology/parasitology ; Feces/parasitology ; Female ; Humans ; *Immunocompromised Host ; Intestinal Diseases, Parasitic/*epidemiology/immunology/*parasitology ; Iran/epidemiology ; Male ; Prevalence ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to determine the status of intestinal parasitic infections in immunocompromised patients in Bushehr province, southwest Iran by conventional and molecular methods.<br><br>METHODS: A total of 201 stool samples were collected from kidney transplant recipients, AIDS patients and patients under chemotherapy. Samples were collected from healthy people as the control group. The specimens were tested using various conventional methods. Polymerase chain reaction (PCR) testing was performed on samples identified as positive for Coccidia by direct microscopic examination.<br><br>RESULTS: Approximately 32.45% were infected with at least one type of intestinal parasite. The highest (46.8%) and lowest rates of infection (24%) were observed in AIDS and chemotherapy patients, respectively, while the infection rate of the control group was 16%. Isospora spp. and Cryptosporidium spp. were observed in all patient groups, and Sarcocystis spp. sporocysts were detected in one of the transplant recipients. All identified coccidia were confirmed by PCR. There was a significant relationship between the rate of intestinal parasite infection and certain variables.<br><br>CONCLUSION: Given the potential risk of certain intestinal parasites in people with immune deficiency, it is recommended that diagnosis of parasitic infections in such patients be based on specific parasitological methods. Thus, it is advisable that physicians refer them to a parasitology laboratory prior to drug administration.}, }
@article {pmid34101828, year = {2021}, author = {Fillon, M}, title = {Fecal microbiota transplants may aid melanoma immunotherapy resistance.}, journal = {CA: a cancer journal for clinicians}, volume = {71}, number = {4}, pages = {285-286}, doi = {10.3322/caac.21676}, pmid = {34101828}, issn = {1542-4863}, mesh = {Humans ; Fecal Microbiota Transplantation ; Immunotherapy ; *Melanoma/therapy ; *Microbiota ; }, }
@article {pmid34100344, year = {2022}, author = {Santos-Paulo, S and Costello, SP and Forster, SC and Travis, SP and Bryant, RV}, title = {The gut microbiota as a therapeutic target for obesity: a scoping review.}, journal = {Nutrition research reviews}, volume = {35}, number = {2}, pages = {207-220}, doi = {10.1017/S0954422421000160}, pmid = {34100344}, issn = {1475-2700}, mesh = {Humans ; *Gastrointestinal Microbiome ; Prebiotics ; Obesity/therapy/metabolism ; Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; }, abstract = {There is mounting evidence that microbiome composition is intimately and dynamically connected with host energy balance and metabolism. The gut microbiome is emerging as a novel target for counteracting the chronically positive energy balance in obesity, a disease of pandemic scale which contributes to >70 % of premature deaths. This scoping review explores the potential for therapeutic modulation of gut microbiota as a means of prevention and/or treatment of obesity and obesity-associated metabolic disorders. The evidence base for interventional approaches which have been shown to affect the composition and function of the intestinal microbiome is summarised, including dietary strategies, oral probiotic treatment, faecal microbiota transplantation and bariatric surgery. Evidence in this field is still largely derived from preclinical rodent models, but interventional studies in obese populations have demonstrated metabolic improvements effected by microbiome-modulating treatments such as faecal microbiota transplantation, as well as drawing attention to the unappreciated role of microbiome modulation in well-established anti-obesity interventions, such as dietary change or bariatric surgery. The complex relationship between microbiome composition and host metabolism will take time to unravel, but microbiome modulation is likely to provide a novel strategy in the limited armamentarium of effective treatments for obesity.}, }
@article {pmid34099716, year = {2021}, author = {Choi, BS and Daniel, N and Houde, VP and Ouellette, A and Marcotte, B and Varin, TV and Vors, C and Feutry, P and Ilkayeva, O and Ståhlman, M and St-Pierre, P and Bäckhed, F and Tremblay, A and White, PJ and Marette, A}, title = {Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3377}, pmid = {34099716}, issn = {2041-1723}, support = {FDN-143247//CIHR/Canada ; }, mesh = {Animal Feed/adverse effects ; Animals ; Cell Line, Tumor ; Diet, High-Fat/adverse effects ; Diet, Western/adverse effects ; Dietary Proteins/*adverse effects ; Dietary Sucrose/adverse effects ; Disease Models, Animal ; Fatty Acids/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Gluconeogenesis ; Hepatocytes ; Humans ; *Insulin Resistance ; Liver/metabolism/pathology ; Male ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Obesity/*etiology/metabolism/pathology ; Rats ; Ribosomal Protein S6 Kinases, 90-kDa/metabolism ; Signal Transduction ; }, abstract = {Animal models of human diseases are classically fed purified diets that contain casein as the unique protein source. We show that provision of a mixed protein source mirroring that found in the western diet exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling as compared to casein alone. These effects involve alterations in gut microbiota as shown by fecal microbiota transplantation studies. The detrimental impact of the mixed protein source is also linked with early changes in microbial production of branched-chain fatty acids (BCFA) and elevated plasma and hepatic acylcarnitines, indicative of aberrant mitochondrial fatty acid oxidation. We further show that the BCFA, isobutyric and isovaleric acid, increase glucose production and activate mTORC1/S6K1 in hepatocytes. Our findings demonstrate that alteration of dietary protein source exerts a rapid and robust impact on gut microbiota and BCFA with significant consequences for the development of obesity and insulin resistance.}, }
@article {pmid34096956, year = {2021}, author = {Han, Z and Yao, L and Zhong, Y and Xiao, Y and Gao, J and Zheng, Z and Fan, S and Zhang, Z and Gong, S and Chang, S and Cui, X and Cai, J}, title = {Gut microbiota mediates the effects of curcumin on enhancing Ucp1-dependent thermogenesis and improving high-fat diet-induced obesity.}, journal = {Food &amp; function}, volume = {12}, number = {14}, pages = {6558-6575}, doi = {10.1039/d1fo00671a}, pmid = {34096956}, issn = {2042-650X}, mesh = {Animals ; Anti-Obesity Agents/pharmacology ; Bile Acids and Salts/metabolism ; Curcumin/*pharmacology ; Diet, High-Fat/adverse effects ; Energy Metabolism/drug effects ; G-Protein-Coupled Receptor Kinase 5/metabolism ; Gastrointestinal Microbiome/*drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/*drug therapy/metabolism ; Thermogenesis/*drug effects ; Uncoupling Protein 1/*metabolism ; Weight Gain/drug effects ; }, abstract = {Due to extremely poor systemic bioavailability, the mechanism by which curcumin increases energy expenditure remains unelucidated. Accumulating evidence suggests a strong association between the gut microbiota (GM) and energy metabolism. We investigated whether the GM mediates the effects of curcumin on improving energy homeostasis. High-fat diet (HFD)-fed wild type, uncoupling protein 1 (Ucp1) knockout and G protein-coupled membrane receptor 5 (TGR5) knockout mice were treated with curcumin (100 mg kg[-1] d[-1], p.o.). Curcumin-treated HFD-fed mice displayed decreased body weight gain and augmented cold tolerance due to enhanced adaptive thermogenesis as compared with that in control mice. The anti-obesity effects of curcumin were abolished by Ucp1 knockout. 16S ribosomal DNA sequencing analysis revealed that curcumin restructured the GM in HFD-fed mice. Fecal microbiota transplantation (FMT) and endogenous GM depletion indicated that the GM mediated the enhanced effect of curcumin on Ucp1-dependent thermogenesis. Curcumin altered bile acid (BA) metabolism with increased fractions of circulating deoxycholic acid (DCA) and lithocholic acid (LCA), which are the two most potent ligands for TGR5. Consistently, the enhanced effect of curcumin on Ucp1-dependent thermogenesis was eliminated by TGR5 knockout. Curcumin requires the GM and TGR5 to activate the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in thermogenic adipose tissue. Here, we demonstrated that the GM mediates the effects of curcumin on enhancing Ucp1-dependent thermogenesis and ameliorating HFD-induced obesity by influencing BA metabolism. We disclosed the potential of nutritional and pharmacologic manipulations of the GM to enhance Ucp1-dependent thermogenesis in the prevention and treatment of obesity.}, }
@article {pmid34093740, year = {2021}, author = {Fu, Y and Luo, Y and Grinspan, AM}, title = {Epidemiology of community-acquired and recurrent Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211016248}, pmid = {34093740}, issn = {1756-283X}, abstract = {Clostridioides difficile infection is a leading cause of healthcare-associated infections with significant morbidity and mortality. For the past decade, the bulk of infection prevention and epidemiologic surveillance efforts have been directed toward mitigating hospital-acquired C. difficile. However, the incidence of community-associated infection is on the rise. Patients with community-associated C. difficile tend to be younger and have lower mortality rate. Rates of recurrent C. difficile infection overall have decreased in the United States, but future research and public health endeavors are needed to standardize and improve disease detection, stratify risk factors in large-scale population studies, and to identify regional and local variations in strain types, reservoirs and transmission routes to help characterize and combat the changing epidemiology of C. difficile.}, }
@article {pmid34092246, year = {2021}, author = {Wu, Y and He, F and Zhang, C and Zhang, Q and Su, X and Zhu, X and Liu, A and Shi, W and Lin, W and Jin, Z and Yang, H and Lin, J}, title = {Melatonin alleviates titanium nanoparticles induced osteolysis via activation of butyrate/GPR109A signaling pathway.}, journal = {Journal of nanobiotechnology}, volume = {19}, number = {1}, pages = {170}, pmid = {34092246}, issn = {1477-3155}, support = {81871789//National Natural Science Foundation of China/ ; 31771063//National Natural Science Foundation of China (CN)/ ; 81802200//National Natural Science Foundation of China (CN)/ ; 82171333//National Natural Science Foundation of China (CN)/ ; 82101033//National Natural Science Foundation of China (CN)/ ; BK20180052//Natural Science Foundation of Jiangsu Province (CN)/ ; GSWS2020023//Gusu Health Talents Program/ ; }, mesh = {Animals ; Butyrates/*metabolism ; Fatty Acids, Volatile ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects ; Homeostasis ; Male ; Melatonin/chemistry/metabolism/*pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Nanoparticles/chemistry/therapeutic use ; Osteolysis/metabolism/pathology/*prevention &amp; control ; RNA, Ribosomal, 16S ; Receptors, G-Protein-Coupled/*genetics/*metabolism ; Signal Transduction/*drug effects ; Titanium/chemistry/metabolism/*pharmacology ; }, abstract = {BACKGROUND: Inflammatory osteolysis after total joint replacement (TJR) may cause implant failure, periprosthetic fractures, and be a severe threat to global public health. Our previous studies demonstrated that melatonin had a therapeutic effect on wear-particles induced osteolysis. Gut microbiota is closely related to bone homeostasis, and has been proven to be affected by melatonin. However, whether melatonin could play its anti-osteolysis effects through reprogramming gut microbiota remains elusive.<br><br>RESULTS: Here, we demonstrated that melatonin could alleviate Ti-particles induced osteolysis, while this therapeutic effect was blocked by antibiotic cocktail treatment. Interestingly, transplantation of fecal microbiota from mice treated with melatonin reappeared the same beneficial effect. Analysis of the 16S rRNA revealed that melatonin could reverse dysbacteriosis triggered by osteolysis, and elevate the relative abundance of some short chain fatty acid (SCFA) producing bacteria. Moreover, butyrate was enriched by exogenous melatonin administration, while acetate and propionate did not show an evident difference. This was consistent with the results of the metagenomic approach (PICRUSt2) analysis, which revealed a general increase in the synthetic enzymes of butyrate. More importantly, direct supplementation of butyrate could also recapitulate the anti-osteolysis effect of melatonin. Further analysis identified that butyrate alleviated osteolysis via activating its receptor GPR109A, and thus to suppress the activation of NLRP3 inflammasome triggered by Ti-particles.<br><br>CONCLUSIONS: Taken together, our results suggested that the benefits of melatonin mainly depend on the ability of modulating gut microbiota and regulating butyrate production.}, }
@article {pmid34090885, year = {2021}, author = {Ianiro, G and Giambò, F and Cammarota, G}, title = {Residual Gastrointestinal Symptoms after Fecal Microbiota Transplantation for Clostridioides difficile Infection: A Matter of Efficacy Rather Than Safety?.}, journal = {Gastroenterology}, volume = {161}, number = {4}, pages = {1344}, doi = {10.1053/j.gastro.2021.06.002}, pmid = {34090885}, issn = {1528-0012}, mesh = {*Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases ; Humans ; }, }
@article {pmid34089791, year = {2021}, author = {Wang, J and Zheng, S and Yang, X and Huazeng, B and Cheng, Q}, title = {Influences of non-IgE-mediated cow's milk protein allergy-associated gut microbial dysbiosis on regulatory T cell-mediated intestinal immune tolerance and homeostasis.}, journal = {Microbial pathogenesis}, volume = {158}, number = {}, pages = {105020}, doi = {10.1016/j.micpath.2021.105020}, pmid = {34089791}, issn = {1096-1208}, mesh = {Animals ; Cattle ; Dysbiosis ; Female ; *Gastrointestinal Microbiome ; Homeostasis ; Immune Tolerance ; Mice ; *Milk Hypersensitivity ; RNA, Ribosomal, 16S/genetics ; T-Lymphocytes, Regulatory ; }, abstract = {Gut microbial dysbiosis is closely associated with cow's milk protein allergy (CMPA) during infancy. Recent research has highlighted the crucial role of the commensal microbiota-induced intestinal regulatory T (Treg) cell response in the development of oral tolerance and protection against IgE-mediated food allergies. However, the influences of CMPA (particularly non-IgE-mediated CMPA)-associated microbial dysbiosis on Treg cell-mediated intestinal immune tolerance and homeostasis remain poorly characterized. To investigate this issue, fecal microbiota from infant donors with food protein-induced allergic proctocolitis (FPIAP) associated with cow's milk, which is the most frequent clinical type of non-IgE-mediated gastrointestinal CMPA, and from age-matched healthy controls were transplanted into germ-free mice in this study. Two weeks post fecal microbiota transplantation, the gut microbiome of the recipient mice was analyzed by 16S rRNA gene sequencing, and the intestinal immunological alterations associated with the Treg cell compartment and intestinal immune homeostasis were detected. The specific gut microbial phylotypes that were potentially responsible for the disruption of intestinal immune homeostasis were also analyzed. We observed that the main characteristics of the gut microbiome in infant donors could be stably maintained in recipient mice. We also found that mice colonized with the gut microbiome from infants with cow's milk-induced FPIAP showed significant deficiencies in the accumulation and function of intestinal Treg cells. Furthermore, these mice showed disrupted intestinal immune homeostasis, which was characterized by an overactivated Th2 biased immune response. We further identified two potentially pathogenic genera that contribute to this disruption. Overall, our results highlight a destructive effect of non-IgE-mediated CMPA-associated microbial dysbiosis on intestinal immune tolerance and homeostasis. We believe these findings will help improve our understanding of the gut microbiota-mediated pathogenesis of non-IgE-mediated CMPA in the future.}, }
@article {pmid34089134, year = {2022}, author = {Mendelsohn, RB and Kaltsas, A and King, S and Hwang, C and Kassam, Z and Abend, AM and Kramer, E and Kamboj, M}, title = {Fecal Microbiota Transplantation Is Safe for Clostridiodies difficile Infection in Patients with Solid Tumors Undergoing Chemotherapy.}, journal = {Digestive diseases and sciences}, volume = {67}, number = {6}, pages = {2503-2509}, pmid = {34089134}, issn = {1573-2568}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; Infant ; *Neoplasms/etiology/therapy ; Prospective Studies ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Recurrent Clostridiodies difficile infection (CDI) contributes to morbidity and mortality in cancer patients. Fecal microbiota transplantation (FMT) has been proven to be effective in treatment of recurrent CDI, but immunocompromised patients have been excluded from prospective studies due to safety concerns. The aim of this study was to investigate the safety of FMT for recurrent CDI in immunocompromised patients with solid tumor malignancy undergoing chemotherapy.<br><br>METHODS: This was a single center, prospective observational study of patients at a tertiary care cancer center of 10 patients with recurrent CDI who were at least 18&#xa0;years of age, with a solid tumor malignancy who had received chemotherapy within the previous 6&#xa0;months. Patients received FMT either by upper endoscopy or colonoscopy and were followed for 6&#xa0;months. Safety was a primary outcome measured by infections occurring within 2&#xa0;weeks of FMT. Efficacy of FMT was also evaluated.<br><br>RESULTS: Nineteen patients were evaluated. On applying exclusion criteria, 10 were included in the study. One patient requested to be off study within 2&#xa0;weeks and was considered a treatment failure. Seven received FMT via upper endoscopy, three via colonoscopy. There were no infectious complications from FMT. Eight patients (80%) were cured after the first FMT. All eight patients went on to restart oncologic treatment with an average of 32.5&#xa0;days after FMT.<br><br>CONCLUSIONS: FMT is safe and effective for recurrent CDI in solid tumor patients undergoing chemotherapy. Patients can resume oncologic treatment after FMT.}, }
@article {pmid34088413, year = {2021}, author = {Khanna, S and Tande, A and Rubin, DT and Khoruts, A and Kahn, SA and Pardi, DS}, title = {Fecal Microbiota Transplantation for Recurrent C difficile Infection During the COVID-19 Pandemic: Experience and Recommendations.}, journal = {Mayo Clinic proceedings}, volume = {96}, number = {6}, pages = {1418-1425}, pmid = {34088413}, issn = {1942-5546}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R24 AI118629/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; COVID-19/diagnosis/*epidemiology/prevention &amp; control ; *Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; SARS-CoV-2 ; Young Adult ; }, abstract = {OBJECTIVE: To report experience with fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) and provide recommendations for management of rCDI and donor testing during the COVID-19 pandemic.<br><br>METHODS: A retrospective study of patients with rCDI who underwent FMT from May 26, 2020, to September 30, 2020, with stool from well-screened donors with health and infectious screening and a newly implemented strategy for COVID-19 screening with every 2-week bookend testing with stool quarantine. Patients were followed up for development of rCDI and COVID-19.<br><br>RESULTS: Of the 57 patients who underwent FMT for rCDI, 29 were tested for COVID-19 via nasopharyngeal polymerase chain reaction (PCR) and 22 via serology. All results were negative, except for 1 positive serology. Donor testing every 2 weeks for COVID-19 via serology and nasopharyngeal swab PCR was negative, except for 2 donors at 1 center who were excluded. Three patients had rCDI after FMT, and 1 underwent repeat FMT. One patient developed respiratory symptoms suggestive of COVID-19 and tested negative via nasopharyngeal PCR. Eleven patients who underwent COVID-19 testing for elective procedures or hospitalizations tested negative. No SARS-CoV-2 transmission was noted.<br><br>CONCLUSIONS: With appropriate donor screening, FMT can be performed safely for rCDI during the COVID-19 pandemic. Development of a validated stool assay for SARS-CoV-2 will simplify this process further.}, }
@article {pmid34087350, year = {2021}, author = {Li, Q and Cui, Y and Xu, B and Wang, Y and Lv, F and Li, Z and Li, H and Chen, X and Peng, X and Chen, Y and Wu, E and Qu, D and Jian, Y and Si, H}, title = {Main active components of Jiawei Gegen Qinlian decoction protects against ulcerative colitis under different dietary environments in a gut microbiota-dependent manner.}, journal = {Pharmacological research}, volume = {170}, number = {}, pages = {105694}, doi = {10.1016/j.phrs.2021.105694}, pmid = {34087350}, issn = {1096-1186}, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Bacteria/*drug effects/growth &amp; development/metabolism ; Colitis, Ulcerative/*drug therapy/metabolism/microbiology/pathology ; Colon/*drug effects/metabolism/microbiology/pathology ; Cytokines/metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal/*pharmacology ; Dysbiosis ; Female ; Gastrointestinal Agents/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Inflammation Mediators/metabolism ; Male ; Oxidative Stress/drug effects ; Rats, Sprague-Dawley ; Rats ; }, abstract = {As an effective drug against acute enteritis diarrhea, Gegen Qinlian decoction (GQD) has a history of 2000 years. However, the potential molecular mechanism through which GQD could protect intestinal barrier from ulcerative colitis (UC) still remains undefined. As an important part of the homeostasis of the colon, gut microbiota is closely related to the dynamic evolution of the surrounding environment and the adjustment of dietary structure. At present, the effectiveness and mechanism of Jiawei Gegen Qinlian decoction against UC in different dietary environments are not clear. Here, the main active components of Jiawei Gegen Qinlian Decoction (PBM), were selected to construct a reasonable and effective compound scheme. We adopted "5% dextran sulfate sodium (DSS)" and "high temperature and humidity + high sugar and high fat + alcohol + 5%DSS" to induce UC rat models in general environment and UC rat models in Lingnan area, respectively. Then, we examined the therapeutic effects of PBM (89.96 mg/kg and 179.92 mg/kg) on two kinds of UC rats. The role of gut microbiota in the anti-UC effect of PBM was identified by intestinal flora consumption and fecal microbiota transplantation (FMT) experiments. Subsequently, we monitored the alterations of gut microbiota and fecal metabolism in the rat colon by 16Sr DNA technique and targeted metabonomics, respectively. The colon inflammation of the PBM-treated and the FMT-treated rats both showed significant relief, as evidenced by a reduction in body weight loss, bloody stool, diarrhea, disease activity index (DAI) score, shortening of colon length as well as decreased colon histology damage. Interestingly enough, the depletion of intestinal flora took away the protective effect of PBM, confirming the importance of intestinal flora in the anti-UC effect of PBM. Then our findings suggested that PBM could not only regulate the gut microbiota by increasing Akkermansia and Romboutsia but also decrease Escherichia-Shigella. More importantly, PBM could increase the production of propionate and total short-chain fatty acids (SCFAs) in colitis rats, regulate medium and long chain fatty acids (M-LCFAs), maintain bile acids (BAs) homeostasis, and regulate amino acids (AAs) metabolism. The transformation of intestinal environment might be related to the upregulation of anti-inflammation, anti-oxidation and tight junction protein expression in colonic mucosa. In summary, PBM showed potential for anti-UC activity through gut microbiota dependence and was expected to be a complementary and alternative medicine herb therapy.}, }
@article {pmid34086219, year = {2021}, author = {Müssig, K}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {163}, number = {11}, pages = {26-27}, doi = {10.1007/s15006-021-0069-3}, pmid = {34086219}, issn = {1613-3560}, mesh = {Body Weight ; *Diet ; *Fecal Microbiota Transplantation ; Humans ; Weight Gain ; }, }
@article {pmid34083249, year = {2021}, author = {Soto-Pantoja, DR and Gaber, M and Arnone, AA and Bronson, SM and Cruz-Diaz, N and Wilson, AS and Clear, KYJ and Ramirez, MU and Kucera, GL and Levine, EA and Lelièvre, SA and Chaboub, L and Chiba, A and Yadav, H and Vidi, PA and Cook, KL}, title = {Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis.}, journal = {Cancer research}, volume = {81}, number = {14}, pages = {3890-3904}, pmid = {34083249}, issn = {1538-7445}, support = {R01 CA253329/CA/NCI NIH HHS/United States ; P30 CA012197/CA/NCI NIH HHS/United States ; R21 CA249349/CA/NCI NIH HHS/United States ; T32 OD010957/OD/NIH HHS/United States ; K12 GM102773/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Breast/*physiopathology ; Carcinogenesis ; Diet, High-Fat/*adverse effects ; Female ; Humans ; Mice ; Microbiota ; Signal Transduction ; }, abstract = {Obesity and poor diet often go hand-in-hand, altering metabolic signaling and thereby impacting breast cancer risk and outcomes. We have recently demonstrated that dietary patterns modulate mammary microbiota populations. An important and largely open question is whether the microbiome of the gut and mammary gland mediates the dietary effects on breast cancer. To address this, we performed fecal transplants between mice on control or high-fat diets (HFD) and recorded mammary tumor outcomes in a chemical carcinogenesis model. HFD induced protumorigenic effects, which could be mimicked in animals fed a control diet by transplanting HFD-derived microbiota. Fecal transplants altered both the gut and mammary tumor microbiota populations, suggesting a link between the gut and breast microbiomes. HFD increased serum levels of bacterial lipopolysaccharide (LPS), and control diet-derived fecal transplant reduced LPS bioavailability in HFD-fed animals. In vitro models of the normal breast epithelium showed that LPS disrupts tight junctions (TJ) and compromises epithelial permeability. In mice, HFD or fecal transplant from animals on HFD reduced expression of TJ-associated genes in the gut and mammary gland. Furthermore, infecting breast cancer cells with an HFD-derived microbiome increased proliferation, implicating tumor-associated bacteria in cancer signaling. In a double-blind placebo-controlled clinical trial of patients with breast cancer administered fish oil supplements before primary tumor resection, dietary intervention modulated the microbiota in tumors and normal breast tissue. This study demonstrates a link between the gut and breast that mediates the effect of diet on cancer. SIGNIFICANCE: This study demonstrates that diet shifts the microbiome in the gut and the breast tumor microenvironment to affect tumorigenesis, and oral dietary interventions can modulate the tumor microbiota in patients with breast cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/14/3890/F1.large.jpg.}, }
@article {pmid34079458, year = {2021}, author = {Li, Q and Ding, X and Liu, Y and Marcella, C and Dai, M and Zhang, T and Bai, J and Xiang, L and Wen, Q and Cui, B and Zhang, F}, title = {Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn's Disease.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {658087}, pmid = {34079458}, issn = {1663-9812}, abstract = {Background: How to handle patients with anti-tumor necrosis factor (anti-TNF) failure was a common challenge to clinicians in Crohn's disease (CD). The present study is dedicated to clarifying whether fecal microbiota transplantation (FMT) could be a switch therapy for patients with prior failure of infiiximab (IFX) in CD in a long-term observation. Methods: Thirty-six patients with CD who had prior failure of IFX were recruited from January 2013 to December 2019. The "one-hour FMT protocol" was followed in all patients. All patients received the first course of FMT through gastroscopy or mid-gut transendoscopic enteral tubing. After April 2014, the methodology of FMT was coined as washed microbiota transplantation (WMT), substituting for the manual methods, which is dependent on the automatic microbiota purification system and the washing process. The primary endpoint of this study was the clinical remission at one month and one year after FMT. The secondary endpoint was the safety of FMT in the short and long term, and clinical factors as predictors for long-term efficacy of FMT. Clinical factors as independent predictors of efficacy from FMT were isolated using univariable and multivariable logistic regression analysis. Results: There was no significant difference in the rates of clinical response and remission between IFX treatment stage and FMT treatment stage (at one month, three months and six months after administration) (p > 0.05). Compared with those of 19 patients who achieved clinical remission at one month after FMT, the rates of clinical relapse were significantly higher in 18 patients who achieved clinical remission at one month after IFX [log-rank test p = 0.0009 HR = 3.081 (95% CI 1.43-6.639)]. Multivariate analysis revealed that the gender of donor (95% CI: 0.001-0.72; p = 0.031) was an independent predictor of efficacy at one year after FMT. No serious adverse events (AEs) associated with FMT were observed during and after FMT. The rate of AEs was significantly lower in group FMT than that in group IFX (p = 0.002). Conclusion: The present findings first time provided the evidence for clinicians to consider FMT into practice as an alternative switch therapy for patients with prior loss of response or intolerance to IFX in CD. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT01793831.}, }
@article {pmid34078971, year = {2021}, author = {Skaarud, KJ and Hov, JR and Hansen, SH and Kummen, M and Valeur, J and Seljeflot, I and Bye, A and Paulsen, V and Lundin, KEA and Trøseid, M and Tjønnfjord, GE and Iversen, PO}, title = {Mortality and microbial diversity after allogeneic hematopoietic stem cell transplantation: secondary analysis of a randomized nutritional intervention trial.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {11593}, pmid = {34078971}, issn = {2045-2322}, mesh = {Adult ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation/mortality ; Humans ; Male ; Middle Aged ; *Nutritional Support ; Transplantation, Homologous ; Young Adult ; }, abstract = {Gut mucosal barrier injury is common following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and associated with poor clinical outcomes. Diet is critical for microbial diversity, but whether nutritional support affects microbiota and outcome after allo-HSCT is unknown. We present a secondary analysis of a randomized controlled nutritional intervention trial during allo-HSCT. We investigated if the intervention influenced gut microbiota, short-chain fatty acids (SCFAs), and markers of gut barrier functions, and if these parameters were associated with clinical outcomes. Fecal specimens were available from 47 recipients, and subjected to 16S rRNA gene sequencing. We found no significant differences between the intervention group and controls in investigated parameters. We observed a major depletion of microbiota, SCFAs, and altered markers of gut barrier function from baseline to 3 weeks post-transplant. One-year mortality was significantly higher in patients with lower diversity at 3 weeks post-HSCT, but not related to diversity at baseline. The relative abundance of Blautia genus at 3 weeks was higher in survivors. Fecal propionic acid was associated with survival. Markers of gut barrier functions were less strongly associated with clinical outcomes. Possibly, other strategies than dietary intervention are needed to prevent negative effects of gut microbiota and clinical outcomes after allo-HSCT.ClinicalTrials.gov (NCT01181076).}, }
@article {pmid34078628, year = {2021}, author = {Lécuyer, E and Le Roy, T and Gestin, A and Lacombe, A and Philippe, C and Ponnaiah, M and Huré, JB and Fradet, M and Ichou, F and Boudebbouze, S and Huby, T and Gautier, E and Rhimi, M and Maguin, E and Kapel, N and Gérard, P and Venteclef, N and Garlatti, M and Chassaing, B and Lesnik, P}, title = {Tolerogenic Dendritic Cells Shape a Transmissible Gut Microbiota That Protects From Metabolic Diseases.}, journal = {Diabetes}, volume = {70}, number = {9}, pages = {2067-2080}, pmid = {34078628}, issn = {1939-327X}, mesh = {Animals ; Dendritic Cells/*metabolism/pathology ; Diet, High-Fat ; Gastrointestinal Microbiome/*physiology ; Inflammation/*metabolism/pathology ; Male ; Metabolic Diseases/*metabolism/pathology ; Mice ; Mice, Transgenic ; Obesity/*metabolism/pathology ; }, abstract = {Excess chronic contact between microbial motifs and intestinal immune cells is known to trigger a low-grade inflammation involved in many pathologies such as obesity and diabetes. The important skewing of intestinal adaptive immunity in the context of diet-induced obesity (DIO) is well described, but how dendritic cells (DCs) participate in these changes is still poorly documented. To address this question, we challenged transgenic mice with enhanced DC life span and immunogenicity (DC[hBcl-2] mice) with a high-fat diet. Those mice display resistance to DIO and metabolic alterations. The DIO-resistant phenotype is associated with healthier parameters of intestinal barrier function and lower intestinal inflammation. DC[hBcl-2] DIO-resistant mice demonstrate a particular increase in tolerogenic DC numbers and function, which is associated with strong intestinal IgA, T helper 17, and regulatory T-cell immune responses. Microbiota composition and function analyses reveal that the DC[hBcl-2] mice microbiota is characterized by lower immunogenicity and an enhanced butyrate production. Cohousing experiments and fecal microbial transplantations are sufficient to transfer the DIO resistance status to wild-type mice, demonstrating that maintenance of DCs' tolerogenic ability sustains a microbiota able to drive DIO resistance. The tolerogenic function of DCs is revealed as a new potent target in metabolic disease management.}, }
@article {pmid34077717, year = {2021}, author = {Hanssen, NMJ and de Vos, WM and Nieuwdorp, M}, title = {Fecal microbiota transplantation in human metabolic diseases: From a murky past to a bright future?.}, journal = {Cell metabolism}, volume = {33}, number = {6}, pages = {1098-1110}, doi = {10.1016/j.cmet.2021.05.005}, pmid = {34077717}, issn = {1932-7420}, mesh = {Clostridium Infections/*therapy ; Colitis, Ulcerative/*therapy ; Diabetes Mellitus, Type 1/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; }, abstract = {Fecal microbiota transplantation (FMT) is gaining considerable traction as a therapeutic approach to influence the course of a plethora of chronic conditions, ranging from metabolic syndrome and malignancies to auto-immune and neurological diseases, and helped to establish the contribution of the gut microbiome to these conditions. Although FMT procedures have yielded important mechanistic insights, their use in clinical practice may be limited due to practical objections in the setting of metabolic diseases. While its applicability is established to treat recurrent Clostridiodes difficile, FMT is emerging in ulcerative colitis and various other diseases. A particularly new insight is that FMTs may not only alter insulin sensitivity but may also alter the course of type 1 diabetes by attenuating underlying auto-immunity. In this review, we will outline the major principles and pitfalls of FMT and where optimization of study design and the procedure itself will further advance the field of cardiometabolic medicine.}, }
@article {pmid34076695, year = {2021}, author = {Sanders, DJ and Inniss, S and Sebepos-Rogers, G and Rahman, FZ and Smith, AM}, title = {The role of the microbiome in gastrointestinal inflammation.}, journal = {Bioscience reports}, volume = {41}, number = {6}, pages = {}, pmid = {34076695}, issn = {1573-4935}, mesh = {Animals ; Autoimmune Diseases/immunology/metabolism/microbiology/therapy ; Bacteria/immunology/*metabolism ; Celiac Disease/immunology/metabolism/microbiology/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/immunology/metabolism/*microbiology/therapy ; *Gastrointestinal Microbiome ; Humans ; Immunity, Mucosal ; Inflammation Mediators/metabolism ; Inflammatory Bowel Diseases/immunology/metabolism/microbiology/therapy ; Intestines/immunology/metabolism/*microbiology ; Metabolic Syndrome/immunology/metabolism/microbiology/therapy ; Pathogen-Associated Molecular Pattern Molecules/metabolism ; Probiotics/therapeutic use ; Signal Transduction ; }, abstract = {The microbiome plays an important role in maintaining human health. Despite multiple factors being attributed to the shaping of the human microbiome, extrinsic factors such diet and use of medications including antibiotics appear to dominate. Mucosal surfaces, particularly in the gut, are highly adapted to be able to tolerate a large population of microorganisms whilst still being able to produce a rapid and effective immune response against infection. The intestinal microbiome is not functionally independent from the host mucosa and can, through presentation of microbe-associated molecular patterns (MAMPs) and generation of microbe-derived metabolites, fundamentally influence mucosal barrier integrity and modulate host immunity. In a healthy gut there is an abundance of beneficial bacteria that help to preserve intestinal homoeostasis, promote protective immune responses, and limit excessive inflammation. The importance of the microbiome is further highlighted during dysbiosis where a loss of this finely balanced microbial population can lead to mucosal barrier dysfunction, aberrant immune responses, and chronic inflammation that increases the risk of disease development. Improvements in our understanding of the microbiome are providing opportunities to harness members of a healthy microbiota to help reverse dysbiosis, reduce inflammation, and ultimately prevent disease progression.}, }
@article {pmid34074837, year = {2021}, author = {Craven, LJ and Parvathy, SN and Burton, JP and Silverman, MS}, title = {Response to Ianiro et al.}, journal = {The American journal of gastroenterology}, volume = {116}, number = {6}, pages = {1361-1362}, doi = {10.14309/ajg.0000000000001160}, pmid = {34074837}, issn = {1572-0241}, mesh = {Fecal Microbiota Transplantation ; Humans ; *Non-alcoholic Fatty Liver Disease ; Permeability ; }, }
@article {pmid34074836, year = {2021}, author = {Ianiro, G and Porcari, S and Gasbarrini, A and Cammarota, G}, title = {Quantity of Donor Stool for Fecal Microbiota Transplantation: The More, the Better?.}, journal = {The American journal of gastroenterology}, volume = {116}, number = {6}, pages = {1360-1361}, doi = {10.14309/ajg.0000000000001130}, pmid = {34074836}, issn = {1572-0241}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Non-alcoholic Fatty Liver Disease ; Permeability ; }, }
@article {pmid34074214, year = {2021}, author = {Browne, PD and Cold, F and Petersen, AM and Halkjær, SI and Christensen, AH and Günther, S and Hestbjerg Hansen, L}, title = {Engraftment of strictly anaerobic oxygen-sensitive bacteria in irritable bowel syndrome patients following fecal microbiota transplantation does not improve symptoms.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-16}, pmid = {34074214}, issn = {1949-0984}, mesh = {Bacteria/classification/genetics/growth &amp; development/isolation &amp; purification ; Bacteria, Anaerobic/classification/genetics/isolation &amp; purification/*metabolism ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*microbiology/*therapy ; Oxygen/*metabolism ; Treatment Outcome ; }, abstract = {Dysbiosis of the gut microbiome has been correlated with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is being explored as a therapeutic option. Little is known of the mechanisms of engraftment of microbes following FMT and whether the engraftment of certain microbes correlate with clinical improvement in IBS. Microbiome data, from a previously reported placebo-controlled trial of treatment of IBS with FMT or placebo capsules, were used to investigate microbial engraftment 15 days, 1, 3 and 6 months after treatment through assessment of gains, losses and changes in abundance of amplicon sequence variants (ASVs) and microbial diversity (CHAO-1 richness) between the FMT group and the placebo group. These data were compared to changes in IBS Symptom Severity Scores (IBS-SSS). Twelve days of treatment with 25 daily multi-donor FMT capsules induced significant short- and long-term changes in the recipients' microbiomes for at least 6 months, with persistent engraftment of a variety of anaerobic bacteria from keystone genera, such as Faecalibacterium, Prevotella and Bacteroides and increased microbial diversity, particularly in patients with low initial diversity. FMT recipients lost ASVs after treatment, which was seen to a much lesser extent in the placebo group. No ASVs increased to a greater extent between FMT responders and non-responders following treatment. Major long-term changes, lasting for at least 6 months, in the gut microbiomes of IBS patients are seen following treatment with FMT capsules. None of these changes correlated with clinical improvement. The relationship between the microbiome and the etiology of IBS still remains unsolved.}, }
@article {pmid34073695, year = {2021}, author = {Chiu, CW and Tsai, PJ and Lee, CC and Ko, WC and Hung, YP}, title = {Application of Microbiome Management in Therapy for Clostridioides difficile Infections: From Fecal Microbiota Transplantation to Probiotics to Microbiota-Preserving Antimicrobial Agents.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {34073695}, issn = {2076-0817}, support = {MOHW105-CDC-C-114-122113//Ministry of Health and Welfare/ ; MOST 108-2321-B-006-004 and 109-2314-B-006-089-MY//Ministry of Science and Technology/ ; NCKUH-11004029//National Cheng Kung University Hospital/ ; }, abstract = {Oral vancomycin and metronidazole, though they are the therapeutic choice for Clostridioides difficile infections (CDIs), also markedly disturb microbiota, leading to a prolonged loss of colonization resistance to C. difficile after therapy; as a result, their use is associated with a high treatment failure rate and high recurrent rate. An alternative for CDIs therapy contains the delivery of beneficial (probiotic) microorganisms into the intestinal tract to restore the microbial balance. Recently, mixture regimens containing Lactobacillus species, Saccharomyces boulardii, or Clostridium butyricum have been extensively studied for the prophylaxis of CDIs. Fecal microbiota transplantation (FMT), the transfer of (processed) fecal material from healthy donors to patients for treating CDIs, combined with vancomycin was recommended as the primary therapy for multiple recurrent CDIs (rCDIs). Either probiotics or FMT have been utilized extensively in preventing or treating CDIs, aiming at less disturbance in the microbiota to prevent rCDIs after therapy cessation. Otherwise, many newly developed therapeutic agents have been developed and aim to preserve microbiota during CDI treatment to prevent disease recurrence and might be useful in clinical patients with rCDIs in the future.}, }
@article {pmid34073647, year = {2021}, author = {Kouidhi, S and Souai, N and Alhujaily, M and Zidi, O and Kochbati, A and Redissi, A and Belali, TM and Kossai, IE and El Manaa, J and Cherif, A and Mnif, W and Mosbah, A}, title = {Multi-Solvent Extraction Procedure for the Pioneer Fecal Metabolomic Analysis-Identification of Potential Biomarkers in Stable Kidney Transplant Patients.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, pmid = {34073647}, issn = {2075-4418}, abstract = {Metabolic alteration plays a functional role in kidney allograft complications. Metabolomics is a promising high-throughput approach in nephrology but is still limited by the lack of overlap in metabolite coverage. We performed an untargeted fecal metabolomic analysis of forty stable kidney allograft recipients and twenty non-transplant controls. First, we applied the ultra-high performance liquid chromatography (UHPLC) analysis coupled with the Diod Array detector. The potential biomarkers were then collected and identified by gas chromatography-mass spectrometry (GCMS). In order to allow for complete coverage of the fecal polar and non-polar metabolites, the performance of five organic solvents with increasing polarity was investigated successively. UHPLC analysis revealed that the fecal metabolite profiles following the five extractions were significantly different between controls and kidney allografts. GC-MS analysis showed that the best predictors' metabolites belonged mainly to long-chain fatty acids, phenolic compounds, and amino acids. Collectively, our results showed the efficiency of our pioneer method to successfully discriminate stable kidney-transplant recipients from controls. These findings suggest that distinct metabolic profiles mainly affect fatty acid biosynthesis and amino acid metabolism. In such a context, the novel insights into metabolomic investigation may be a valuable tool that could provide useful new relevant biomarkers for preventing kidney transplant complications.}, }
@article {pmid34071229, year = {2021}, author = {Shang, L and Liu, H and Yu, H and Chen, M and Yang, T and Zeng, X and Qiao, S}, title = {Core Altered Microorganisms in Colitis Mouse Model: A Comprehensive Time-Point and Fecal Microbiota Transplantation Analysis.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {34071229}, issn = {2079-6382}, support = {2016YFD0501308//National Key Research and Development Program of China/ ; cstc2019ngzx0019//Chongqing Rongchang Agricultural and Animal Husbandry High-tech Industry Research and Development Project/ ; }, abstract = {Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic and relapsing inflammation within the gastrointestinal tract. Antibiotics have been used to treat IBD, primarily utilizing metronidazole. Although there does seem to be a treatment effect, the broad-spectrum antibiotics that have been used to date are crude tools and have many adverse effects. Available evidence suggests that the host microbiome is implicated in the pathogenesis of IBD, though the key bacteria remain unknown. If the bacterial population can be modified appropriately, the use of antibiotics will have a better therapeutic effect. In this study, mice were fed dextran sodium sulfate (DSS) solution for 5 days, followed by 5 days of normal drinking water, to investigate the gut microbiota response to colitis and the initial alteration of microbiota in recovery phase. Day 0 was considered the normal control, while day 5 and day 10 were considered the colitis mouse model progressive phase and recovery phase, respectively. Results showed that inflammation could induce proportional changes in the gut microbiota. Furthermore, transplanting the microbiota in progressive phase to antibiotic-induced microbiota-depleted mice could induce inflammation similar to colitis, which proves the importance of initial alteration of the microbiota for IBD recovery and the potential of the microbiota as a target for the treatment of IBD. Meanwhile, we have also identified three possible target microorganisms in the development of colitis, namely genera Muribaculaceae (negative correlation), Turicibacter (positive correlation) and Lachnospiraceae (negative correlation) in inflammation status through comprehensive analysis.}, }
@article {pmid34071065, year = {2021}, author = {LeBlanc, JF and Segal, JP and de Campos Braz, LM and Hart, AL}, title = {The Microbiome as a Therapy in Pouchitis and Ulcerative Colitis.}, journal = {Nutrients}, volume = {13}, number = {6}, pages = {}, pmid = {34071065}, issn = {2072-6643}, mesh = {Colitis, Ulcerative/microbiology/*therapy ; Diet, Mediterranean ; Fatty Acids, Omega-3/therapeutic use ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/therapy ; Microbiota ; Pouchitis/microbiology/*therapy ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The gut microbiome has been implicated in a range of diseases and there is a rapidly growing understanding of this ecosystem's importance in inflammatory bowel disease. We are yet to identify a single microbe that causes either ulcerative colitis (UC) or pouchitis, however, reduced microbiome diversity is increasingly recognised in active UC. Manipulating the gut microbiome through dietary interventions, prebiotic and probiotic compounds and faecal microbiota transplantation may expand the therapeutic landscape in UC. Specific diets, such as the Mediterranean diet or diet rich in omega-3 fatty acids, may reduce intestinal inflammation or potentially reduce the risk of incident UC. This review summarises our knowledge of gut microbiome therapies in UC and pouchitis.}, }
@article {pmid34068085, year = {2021}, author = {Haindl, R and Engel, J and Kulozik, U}, title = {Establishment of an In Vitro System of the Human Intestinal Microbiota: Effect of Cultivation Conditions and Influence of Three Donor Stool Samples.}, journal = {Microorganisms}, volume = {9}, number = {5}, pages = {}, pmid = {34068085}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is an alternative method for the treatment of gastrointestinal diseases with a high recovery rate. Disadvantages are ethical concerns, high donor requirements and the low storability of stool samples. The cultivation of an in vitro microbiota in a continuous bioreactor was established as an alternative to FMT to overcome these problems. In this study, the influence of the system parameters and donor stool characteristics was investigated. Each continuous colonic fermentation system was inoculated with feces from three different donors until a stable state was established. The influence of the fermentation conditions on the system's behavior regarding cell count, metabolic activity, short-chain fatty acid profile and microbiota composition as well as richness and diversity was assessed. Cultivation conditions were found to affect the microbial system: the number of cells and the production of short-chain fatty acids increased. The abundance of Actinobacteria and Firmicutes decreased, Bacteroidetes increased, while Proteobacteria and Verrucomicrobia remained largely unaffected. Diversity in the in vitro system decreased, but richness was unaffected. The cultivation of stool from different donors revealed that the performance of the created in vitro system was similar and comparable, but unique characteristics of the composition of the original stool remained.}, }
@article {pmid34067662, year = {2021}, author = {Berlanda, M and Innocente, G and Simionati, B and Di Camillo, B and Facchin, S and Giron, MC and Savarino, E and Sebastiani, F and Fiorio, F and Patuzzi, I}, title = {Faecal Microbiome Transplantation as a Solution to Chronic Enteropathies in Dogs: A Case Study of Beneficial Microbial Evolution.}, journal = {Animals : an open access journal from MDPI}, volume = {11}, number = {5}, pages = {}, pmid = {34067662}, issn = {2076-2615}, support = {POR FESR 2014-2020, Asse 1. Azione 1.1.1., grant number 10232721//This research was funded by EuBiome with a contribution of Regione Veneto (Italy)/ ; }, abstract = {Chronic enteropathies (CE) are gastrointestinal diseases that afflict about one in five dogs in Europe. Conventional therapeutic approaches include dietary intervention, pharmacological treatment and probiotic supplements. The patient response can be highly variable and the interventions are often not resolutive. Moreover, the therapeutic strategy is usually planned (and gradually corrected) based on the patient's response to empirical treatment, with few indirect gut health indicators useful to drive clinicians' decisions. The ever-diminishing cost of high-throughput sequencing (HTS) allows clinicians to directly follow and characterise the evolution of the whole gut microbial community in order to highlight possible weaknesses. In this framework, faecal microbiome transplantation (FMT) is emerging as a feasible solution to CE, based on the implant of a balanced, eubiotic microbial community from a healthy donor to a dysbiotic patient. In this study, we report the promising results of FMT carried out in a 9-year-old dog suffering from CE for the last 3 years. The patient underwent a two-cycle oral treatment of FMT and the microbiota evolution was monitored by 16S rRNA gene sequencing both prior to FMT and after the two administrations. We evaluated the variation of microbial composition by calculating three different alpha diversity indices and compared the patient and donor data to a healthy control population of 94 dogs. After FMT, the patient's microbiome and clinical parameters gradually shifted to values similar to those observed in healthy dogs. Symptoms disappeared during a follow-up period of six months after the second FMT. We believe that this study opens the door for potential applications of FMT in clinical veterinary practice and highlights the need to improve our knowledge on this relevant topic.}, }
@article {pmid34065241, year = {2021}, author = {Malnick, SDH and Fisher, D and Somin, M and Neuman, MG}, title = {Treating the Metabolic Syndrome by Fecal Transplantation-Current Status.}, journal = {Biology}, volume = {10}, number = {5}, pages = {}, pmid = {34065241}, issn = {2079-7737}, abstract = {The intestinal microbiome (IM) is important for normal gastrointestinal (GI) and other organ systems' functioning. An alteration in the normal IM, dysbiosis, and changes in intestinal motility result in microorganisms' overgrowth and an alteration in intestinal permeability. The gut-brain axis is also of importance in the irritable bowel syndrome (IBS) and associated bowel overgrowth. Secondary to the epidemic of obesity, the metabolic syndrome has become a major health problem. Disturbances in the fecal microbiome are associated with the metabolic syndrome. Metabolic-associated fatty liver disease (MAFLD) is now the current terminology for non-alcoholic fatty liver disease. IM alteration by fecal transplantation is an approved treatment method for recurrent Clostridioides difficile infection. Initially performed by either duodenal infusion or colonoscopy, it is now easily performed by the administration of capsules containing stools. We discuss the intestinal microbiome-its composition, as well as the qualitative changes of microbiome composition leading to inflammation. In addition, we discuss the evidence of the effect of fecal transplantation on the metabolic syndrome and MAFLD, as well as its clinical indications.}, }
@article {pmid34061595, year = {2021}, author = {Sato, K and Yamazaki, K and Kato, T and Nakanishi, Y and Tsuzuno, T and Yokoji-Takeuchi, M and Yamada-Hara, M and Miura, N and Okuda, S and Ohno, H and Yamazaki, K}, title = {Obesity-Related Gut Microbiota Aggravates Alveolar Bone Destruction in Experimental Periodontitis through Elevation of Uric Acid.}, journal = {mBio}, volume = {12}, number = {3}, pages = {e0077121}, pmid = {34061595}, issn = {2150-7511}, mesh = {Alveolar Bone Loss/*etiology/pathology ; Animals ; Diet, High-Fat ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/complications/*microbiology ; Periodontitis/etiology/*microbiology ; Risk Factors ; Uric Acid/analysis/*metabolism ; }, abstract = {Obesity is a risk factor for periodontal disease (PD). Initiation and progression of PD are modulated by complex interactions between oral dysbiosis and host responses. Although obesity is associated with increased susceptibility to bacterial infection, the detailed mechanisms that connect obesity and susceptibility to PD remain elusive. Using fecal microbiota transplantation and a ligature-induced PD model, we demonstrated that gut dysbiosis-associated metabolites from high-fat diet (HFD)-fed mice worsen alveolar bone destruction. Fecal metabolomics revealed elevated purine degradation pathway activity in HFD-fed mice, and recipient mice had elevated levels of serum uric acid upon PD induction. Furthermore, PD induction caused more severe bone destruction in hyperuricemic than normouricemic mice, and the worsened bone destruction was completely abrogated by allopurinol, a xanthine oxidase inhibitor. Thus, obesity increases the risk of PD by increasing production of uric acid mediated by gut dysbiosis. IMPORTANCE Obesity is an epidemic health issue with a rapid increase worldwide. It increases the risk of various diseases, including periodontal disease, an oral chronic infectious disease. Although obesity increases susceptibility to bacterial infection, the precise biological mechanisms that link obesity and susceptibility to periodontal disease remain elusive. Using fecal microbial transplantation, experimental periodontitis, and metabolomics, our study demonstrates uric acid as a causative substance for greater aggravation of alveolar bone destruction in obesity-related periodontal disease. Gut microbiota from obese mice upregulated the purine degradation pathway, and the resulting elevation of serum uric acid promoted alveolar bone destruction. The effect of uric acid was confirmed by administration of allopurinol, an inhibitor of xanthine oxidase. Overall, our study provides new insights into the pathogenic mechanisms of obesity-associated periodontal disease and the development of new therapeutic options for the disease.}, }
@article {pmid34061001, year = {2021}, author = {Novais, F and Capela, J and Machado, S and Murillo-Rodriguez, E and Telles-Correia, D}, title = {Does Dysbiosis Increase the Risk of Developing Schizophrenia? - A Comprehensive Narrative Review.}, journal = {Current topics in medicinal chemistry}, volume = {21}, number = {11}, pages = {976-984}, doi = {10.2174/1568026621666210521163555}, pmid = {34061001}, issn = {1873-4294}, mesh = {Brain/*metabolism ; Central Nervous System/growth &amp; development/metabolism ; Dysbiosis/*complications/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/*metabolism ; Intestines/microbiology ; Prebiotics ; Probiotics/metabolism ; Schizophrenia/*etiology ; }, abstract = {BACKGROUND: There is increasing evidence regarding the influence of the intestinal microbiota on the disease processes of various organs and systems. Dysbiosis, that is, alteration of the composition and function of the microbiota may constitute an important risk factor for the development of mental disorders, namely, schizophrenia.<br><br>OBJECTIVE: This works aims to review current evidence regarding the pathological mechanisms leading from dysbiosis to schizophrenia and in particular the deficit syndrome in schizophrenia.<br><br>METHODS: Scientific articles from PubMed, SCOPUS, EMBASE, and Web of Science Core Collection published between September 2017 and December 2020 were included in this review.<br><br>RESULTS: The commensal intestinal flora plays an important role in neurodevelopment. In the presence of dysbiosis, this maturation gets disturbed, resulting in the modification of brain structures and inflammatory responses at the intestinal, systemic, and Central Nervous System (CNS) levels. These disturbances may be linked to the development of symptoms of the disease. The microbiota exerts its influence on the CNS through several pathways, however, in this paper we focused on the membrane hypothesis and the inflammatory hypothesis. We explored the evidence concerning the use of probiotics, prebiotics, and fecal transplants.<br><br>CONCLUSION: Although there is no consensus regarding the alterations that could constitute a risk factor for schizophrenia, some of the species appear to be more frequently altered, and their relationship with the host is dysregulated in patients at risk and with established schizophrenia, particularly in deficit schizophrenia.}, }
@article {pmid34058102, year = {2021}, author = {Horton, LC and Feuerstein, JD}, title = {In recurrent C difficile infection, oral FMT capsules have a pooled cure rate of 82% (low-quality evidence).}, journal = {Annals of internal medicine}, volume = {174}, number = {6}, pages = {JC65}, doi = {10.7326/ACPJ202106150-065}, pmid = {34058102}, issn = {1539-3704}, mesh = {Capsules ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {Du C, Luo Y, Walsh S, Grinspan A. Oral fecal microbiota transplant capsules are safe and effective for recurrent Clostridioides difficile infection: a systematic review and meta-analysis. J Clin Gastroenterol. 2021;55:300-8. 33471490.}, }
@article {pmid34055657, year = {2021}, author = {Mazzawi, T and El-Salhy, M and Lied, GA and Hausken, T}, title = {The Effects of Fecal Microbiota Transplantation on the Symptoms and the Duodenal Neurogenin 3, Musashi 1, and Enteroendocrine Cells in Patients With Diarrhea-Predominant Irritable Bowel Syndrome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {524851}, pmid = {34055657}, issn = {2235-2988}, mesh = {Diarrhea ; Duodenum ; Enteroendocrine Cells ; *Fecal Microbiota Transplantation ; Feces ; Female ; Humans ; *Irritable Bowel Syndrome/therapy ; Male ; Norway ; }, abstract = {INTRODUCTION: Interactions between the gut microbiota and enteroendocrine cells play important role in irritable bowel syndrome (IBS). Reduced stem cell densities and their differentiation into enteroendocrine cells may cause abnormal densities of the duodenal enteroendocrine cells in IBS patients.<br><br>MATERIALS AND METHODS: We aimed to investigate the effects of fecal microbiota transplantation (FMT) on stem cell differentiation into enteroendocrine cells as detected by neurogenin 3, stem cells as detected by Musashi 1, and the enteroendocrine cells in the duodenum of IBS patients. The study included 16 IBS patients according to Rome III criteria. Four patients were excluded. The remaining patients (n = 12, four females and eight males) were divided according to the cause of IBS into post-infectious (n = 6) and idiopathic (n = 6) IBS. They completed the following questionnaires before and 3 weeks after FMT: IBS-Symptom Severity Scoring system (IBS-SSS) and IBS-Symptom Questionnaire (IBS-SQ). Feces donated by healthy relatives of the patients were transplanted via gastroscope. Biopsies were taken from the descending part of the duodenum at baseline and 3 weeks after FMT. They were immunostained for neurogenin 3, Musashi 1, and all types of duodenal enteroendocrine cells and quantified by computerized image analysis. Microbiota analyses of feces collected just before and 3 weeks after FMT were performed using GA-map&#x2122; Dysbiosis test (Genetic Analysis AS, Oslo, Norway).<br><br>RESULTS: The total scores for IBS-SSS and IBS-SQ were significantly improved 3 weeks after receiving FMT, P = 0.0009 and <0.0001, respectively. The stem cell densities of neurogenin 3 increased significantly following FMT (P = 0.0006) but not for Musashi 1 (P = 0.42). The cell densities of chromogranin A, cholecystokinin, gastric inhibitory peptide, serotonin, and somatostatin, but not for secretin, have significantly changed in both IBS groups after 3 weeks from receiving FMT.<br><br>CONCLUSION: More than two-thirds of IBS patients experienced improvement in their symptoms parallel to changes in the enteroendocrine cells densities 3 weeks after FMT. The changes in the enteroendocrine cell densities do not appear to be caused by changes in the stem cells or their early progenitors rather by changes in the differentiation progeny as detected by neurogenin 3. The study was retrospectively registered at ClinicalTrials.gov (ID: NCT03333291).<br><br>CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03333291.}, }
@article {pmid34054866, year = {2021}, author = {Yang, M and Yang, Y and He, Q and Zhu, P and Liu, M and Xu, J and Zhao, M}, title = {Intestinal Microbiota-A Promising Target for Antiviral Therapy?.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {676232}, pmid = {34054866}, issn = {1664-3224}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Antiviral Agents/*therapeutic use ; COVID-19/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Host-Pathogen Interactions ; Humans ; Probiotics/*therapeutic use ; SARS-CoV-2/*physiology ; Virus Diseases/*therapy ; }, abstract = {The intestinal microbiota is thought to be an important biological barrier against enteric pathogens. Its depletion, however, also has curative effects against some viral infections, suggesting that different components of the intestinal microbiota can play both promoting and inhibitory roles depending on the type of viral infection. The two primary mechanisms by which the microbiota facilitates or inhibits viral invasion involve participation in the innate and adaptive immune responses and direct or indirect interaction with the virus, during which the abundance and composition of the intestinal microbiota might be changed by the virus. Oral administration of probiotics, faecal microbiota transplantation (FMT), and antibiotics are major therapeutic strategies for regulating intestinal microbiota balance. However, these three methods have shown limited curative effects in clinical trials. Therefore, the intestinal microbiota might represent a new and promising supplementary antiviral therapeutic target, and more efficient and safer methods for regulating the microbiota require deeper investigation. This review summarizes the latest research on the relationship among the intestinal microbiota, anti-viral immunity and viruses and the most commonly used methods for regulating the intestinal microbiota with the goal of providing new insight into the antiviral effects of the gut microbiota.}, }
@article {pmid34054845, year = {2021}, author = {Bosák, J and Lexa, M and Fiedorová, K and Gadara, DC and Micenková, L and Spacil, Z and Litzman, J and Freiberger, T and Šmajs, D}, title = {Patients With Common Variable Immunodeficiency (CVID) Show Higher Gut Bacterial Diversity and Levels of Low-Abundance Genes Than the Healthy Housemates.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {671239}, pmid = {34054845}, issn = {1664-3224}, mesh = {Adenosine/metabolism ; Biodiversity ; Clostridiaceae/*physiology ; Common Variable Immunodeficiency/genetics/*microbiology ; Computational Biology/*methods ; Dysbiosis/genetics/*microbiology ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Homeostasis ; Humans ; Metabolomics ; Metagenome ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {Common variable immunodeficiency (CVID) is a clinically and genetically heterogeneous disorder with inadequate antibody responses and low levels of immunoglobulins including IgA that is involved in the maintenance of the intestinal homeostasis. In this study, we analyzed the taxonomical and functional metagenome of the fecal microbiota and stool metabolome in a cohort of six CVID patients without gastroenterological symptomatology and their healthy housemates. The fecal microbiome of CVID patients contained higher numbers of bacterial species and altered abundance of thirty-four species. Hungatella hathewayi was frequent in CVID microbiome and absent in controls. Moreover, the CVID metagenome was enriched for low-abundance genes likely encoding nonessential functions, such as bacterial motility and metabolism of aromatic compounds. Metabolomics revealed dysregulation in several metabolic pathways, mostly associated with decreased levels of adenosine in CVID patients. Identified features have been consistently associated with CVID diagnosis across the patients with various immunological characteristics, length of treatment, and age. Taken together, this initial study revealed expansion of bacterial diversity in the host immunodeficient conditions and suggested several bacterial species and metabolites, which have potential to be diagnostic and/or prognostic CVID markers in the future.}, }
@article {pmid34054740, year = {2021}, author = {Ser, HL and Letchumanan, V and Goh, BH and Wong, SH and Lee, LH}, title = {The Use of Fecal Microbiome Transplant in Treating Human Diseases: Too Early for Poop?.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {519836}, pmid = {34054740}, issn = {1664-302X}, abstract = {Fecal microbiome transplant (FMT) has gained popularity over the past few years, given its success in treating several gastrointestinal diseases. At the same time, microbial populations in the gut have been shown to have more physiological effects than we expected as "habitants" of the gut. The imbalance in the gut microbiome or dysbiosis, particularly when there are excessive harmful pathogens, can trigger not just infections but can also result in the development of common diseases, such as cancer and cardiometabolic diseases. By using FMT technology, the dysbiosis of the gut microbiome in patients can be resolved by administering fecal materials from a healthy donor. The current review summarizes the history and current uses of FMT before suggesting potential ideas for its high-quality application in clinical settings.}, }
@article {pmid34053243, year = {2021}, author = {Kang, Y and Kang, X and Zhang, H and Liu, Q and Yang, H and Fan, W}, title = {Gut Microbiota and Parkinson's Disease: Implications for Faecal Microbiota Transplantation Therapy.}, journal = {ASN neuro}, volume = {13}, number = {}, pages = {17590914211016217}, pmid = {34053243}, issn = {1759-0914}, mesh = {Animals ; Dysbiosis/diagnosis/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Parkinson Disease/diagnosis/microbiology/*therapy ; }, abstract = {Parkinson's disease (PD) ranks the second place among neurodegenerative diseases in terms of its morbidity, which affects 1-2% people aged over 65 years. In addition to genetics, some environmental factors may exert vital parts in PD occurrence as well. At present, more and more studies are conducted to elucidate the association between gut microbial dysbiosis and the incidence of PD. Gut microbial dysbiosis has a certain effect on both the central nervous system (CNS) and the enteric nervous system (ENS), which indicates that there is a gut-microbiota-brain axis that induces CNS disorders. Some gut microbial strains are suggested to suppress or weaken the neuroinflammation- and gut-inflammation-immune responses, which suggests the protective and pathogenic effects of certain gut microbial species on PD progression. Therefore, gut microbiome may contain plenty of targets for preventing and managing PD. Faecal microbiota transplantation (FMT) may serve as a direct and useful treatment for PD in the future. Nonetheless, there is little available scientific research in this field. The present work reviewed the latest research to examine the association of gut microbiota with PD, and the future prospects of FMT treatment.}, }
@article {pmid34051351, year = {2022}, author = {Pandya, G and Kirtonia, A and Singh, A and Goel, A and Mohan, CD and Rangappa, KS and Pandey, AK and Kapoor, S and Tandon, S and Sethi, G and Garg, M}, title = {A comprehensive review of the multifaceted role of the microbiota in human pancreatic carcinoma.}, journal = {Seminars in cancer biology}, volume = {86}, number = {Pt 3}, pages = {682-692}, doi = {10.1016/j.semcancer.2021.05.027}, pmid = {34051351}, issn = {1096-3650}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Pancreatic Neoplasms/therapy/pathology ; *Microbiota ; Immunotherapy ; *Antineoplastic Agents ; Tumor Microenvironment ; }, abstract = {Pancreatic carcinoma is associated with one of the worst clinical outcomes throughout the globe because of its aggressive, metastatic, and drug-resistant nature. During the past decade, several studies have shown that oral, gut, and tumor microbiota play a critical role in the modulation of metabolism and immune responses. Growing pieces of evidence have proved beyond a doubt that the microbiota has a unique ability to influence the tumor microenvironment as well as the metabolism of chemotherapeutic agents or drugs. Given this, microbiota, known as the ecological community of microorganisms, stands to be an avenue of quality research. In this review, we provide detailed and critical information on the role of oral, gut, and pancreatic microbiota disruptions in the development of pancreatic carcinoma. Moreover, we comprehensively discuss the different types of microbiota, their potential role, and mechanism associated with pancreatic carcinoma. The microbiome provides the unique opportunity to enhance the effectiveness of chemotherapeutic agents and immunotherapies for pancreatic cancer by maintaining the right type of microbiota and holds a promising future to enhance the clinical outcomes of patients with pancreatic carcinoma.}, }
@article {pmid34051218, year = {2021}, author = {Wang, H and Banerjee, N and Liang, Y and Wang, G and Hoffman, KL and Khan, MF}, title = {Gut microbiome-host interactions in driving environmental pollutant trichloroethene-mediated autoimmunity.}, journal = {Toxicology and applied pharmacology}, volume = {424}, number = {}, pages = {115597}, pmid = {34051218}, issn = {1096-0333}, support = {R01 ES016302/ES/NIEHS NIH HHS/United States ; R01 ES026887/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Autoimmunity/*drug effects ; Bacteria/*drug effects ; Drug Administration Schedule ; Environmental Pollutants/*toxicity ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Inflammation ; Liver/drug effects ; Mice ; Mice, Inbred Strains ; Oxidative Stress ; Spleen/drug effects ; Trichloroethylene/*toxicity ; }, abstract = {Trichloroethene (TCE), a widely used industrial solvent, is associated with the development of autoimmune diseases (ADs), including systemic lupus erythematosus and autoimmune hepatitis. Increasing evidence support a linkage between altered gut microbiome composition and the onset of ADs. However, it is not clear how gut microbiome contributes to TCE-mediated autoimmunity, and initial triggers for microbiome-host interactions leading to systemic autoimmune responses remain unknown. To achieve this, female MRL+/+ mice were treated with 0.5 mg/ml TCE for 52 weeks and fecal samples were subjected to 16S rRNA sequencing to determine the microbiome composition. TCE exposure resulted in distinct bacterial community revealed by β-diversity analysis. Notably, we observed reduction in Lactobacillaceae, Rikenellaceae and Bifidobacteriaceae families, and enrichment of Akkermansiaceae and Lachnospiraceae families after TCE exposure. We also observed significantly increased colonic oxidative stress and inflammatory markers (CD14 and IL-1β), and decreased tight junction proteins (ZO-2, occludin and claudin-3). These changes were associated with increases in serum antinuclear and anti-smooth muscle antibodies and cytokines (IL-6 and IL-12), together with increased PD1 + CD4+ T cells in TCE-exposed spleen and liver tissues. Importantly, fecal microbiota transplantation (FMT) using feces from TCE-treated mice to antibiotics-treated mice induced increased anti-dsDNA antibodies and hepatic CD4+ T cell infiltration in the recipient mice. Our studies thus delineate how imbalance in gut microbiome and mucosal redox status together with gut inflammatory response and permeability changes could be the key factors in contributing to TCE-mediated ADs. Furthermore, FMT studies provide a solid support to a causal role of microbiome in TCE-mediated autoimmunity.}, }
@article {pmid34049374, year = {2022}, author = {Saha, S and Sehgal, K and Singh, S and Grover, M and Pardi, D and Khanna, S}, title = {Postinfection Irritable Bowel Syndrome Following Clostridioides difficile Infection: A Systematic-review and Meta-analysis.}, journal = {Journal of clinical gastroenterology}, volume = {56}, number = {2}, pages = {e84-e93}, pmid = {34049374}, issn = {1539-2031}, support = {K23 DK103911/DK/NIDDK NIH HHS/United States ; R03 DK120745/DK/NIDDK NIH HHS/United States ; }, mesh = {*Clostridium Infections/diagnosis/epidemiology/therapy ; Diarrhea/etiology/microbiology ; Humans ; *Irritable Bowel Syndrome/diagnosis/epidemiology/therapy ; Prospective Studies ; Retrospective Studies ; }, abstract = {BACKGROUND: Postinfection irritable bowel syndrome (PI-IBS) affects ~14% patients after acute bacterial enterocolitis.<br><br>AIM: The aim of this study was to conduct a systematic review and meta-analysis to find the prevalence of PI-IBS following Clostridioides difficile infection (CDI).<br><br>METHODS: We systematically searched Medline, Embase, and Web of Science from inception through January 20, 2020 for cohort studies assessing PI-IBS following CDI. Primary outcome was pooled prevalence calculated using inverse variance heterogeneity model [MetaXL (v. 5.3)]. A priori subgroup analyses were done [by irritable bowel syndrome (IBS) diagnostic criteria-Rome vs. others, time of IBS diagnosis-<6 or >6&#x2009;mo, exclusion or inclusion of pre-existing IBS and CDI treatment-antibiotic with fecal microbiota transplantation vs. antibiotic only]. Heterogeneity was considered substantial if I2>50%.<br><br>RESULTS: From 2007 to 2019, 15 studies were included (10 prospective, 5 retrospective; 9 full-text, 6 abstracts). Data from 1218 patients were included in the quantitative analysis. Risk of bias was low in 7, medium in 4 and high in 4 studies. Pooled prevalence of PI-IBS was 21.1% (95% confidence interval, 8.2%-35.7%), I2=96%. Common PI-IBS subtypes were diarrhea-predominant in 46.3% (50) patients, and mixed in 33.3% (36) patients. Subgroup analyses by IBS diagnostic criteria, time of IBS diagnosis or CDI treatment did not significantly change the primary outcome (all P>0.05), nor decrease heterogeneity. Funnel plot analysis revealed publication bias.<br><br>CONCLUSIONS: Over 20% of patients develop PI-IBS after CDI. Factors such as diagnostic criteria for IBS and CDI treatment did not affect prevalence, though small numbers limit the confidence in these conclusions. Larger, well conducted studies are needed to study PI-IBS in CDI.}, }
@article {pmid34048223, year = {2021}, author = {Liu, J and Zhao, F and Wang, T and Xu, Y and Qiu, J and Qian, Y}, title = {Host Metabolic Disorders Induced by Alterations in Intestinal Flora under Dietary Pesticide Exposure.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {22}, pages = {6303-6317}, doi = {10.1021/acs.jafc.1c00273}, pmid = {34048223}, issn = {1520-5118}, mesh = {Animals ; Dietary Exposure ; *Gastrointestinal Microbiome ; Liver ; Mice ; Obesity ; *Pesticides/toxicity ; }, abstract = {A dietary pesticide residue causes underestimated influences on body health. In this work, experimental mice were exposed to commonly used pesticides that cause insulin resistance, inflammation, and non-alcoholic fatty liver diseases. Alterations in intestinal flora were detected in the exposure groups. The abundance of the flora causing high endotoxin production was intensively increased and led to body inflammation. High Firmicutes/Bacteroidetes and obesity-related flora characteristics were also found. The metabolisms of intestinal flora and host circulation were investigated through metabolomics. The associations of flora with their metabolites and host circulation were also established. Association analysis can determine the influences of pesticide exposure on such a complex system. The affected metabolic pathways in the liver were also determined to clarify the mechanism underlying the effect of pesticide exposure on host physiology. Interventions with fructooligosaccharides and fecal microbiota transplantation alleviated the metabolic disorders, thus directly confirming that the intestinal flora mediates the effects of pesticide exposure on host circulation. This work elucidated the intestinal-flora-mediated effects of dietary pollutant exposure on body health and provided potential measures for regulating flora and host circulation.}, }
@article {pmid34045661, year = {2021}, author = {Qi, R and Sun, J and Qiu, X and Zhang, Y and Wang, J and Wang, Q and Huang, J and Ge, L and Liu, Z}, title = {The intestinal microbiota contributes to the growth and physiological state of muscle tissue in piglets.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {11237}, pmid = {34045661}, issn = {2045-2322}, mesh = {Animals ; Gastrointestinal Microbiome/*physiology ; Gene Expression Profiling ; Insulin-Like Growth Factor I/metabolism ; Muscle, Skeletal/*physiology ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/physiology ; Swine ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {Although the importance of the intestinal microbiota in host growth and health is well known, the relationship between microbiota colonization and muscle development is unclear. In this study, the direct causal effects of the colonization of gut microorganisms on the muscle tissue of piglets were investigated. The body weight and lean mass of germ-free (GF) piglets were approximately 40% lower than those of normal piglets. The deletion of the intestinal microbiota led to weakened muscle function and a reduction in myogenic regulatory proteins, such as MyoG and MyoD, in GF piglets. In addition, the blinded IGF1/AKT/mTOR pathway in GF piglets caused muscle atrophy and autophagy, which were characterized by the high expression of Murf-1 and KLF15. Gut microbiota introduced to GF piglets via fecal microbiota transplantation not only colonized the gut but also partially restored muscle growth and development. Furthermore, the proportion of slow-twitch muscle fibers was lower in the muscle of GF piglets, which was caused by the reduced short-chain fatty acid content in the circulation and impaired mitochondrial function in muscle. Collectively, these findings suggest that the growth, development and function of skeletal muscle in animals are mediated by the intestinal microbiota.}, }
@article {pmid34044101, year = {2021}, author = {Gonzales-Luna, AJ and Spinler, JK and Oezguen, N and Khan, MAW and Danhof, HA and Endres, BT and Alam, MJ and Begum, K and Lancaster, C and Costa, GP and Savidge, TC and Hurdle, JG and Britton, R and Garey, KW}, title = {Systems biology evaluation of refractory Clostridioides difficile infection including multiple failures of fecal microbiota transplantation.}, journal = {Anaerobe}, volume = {70}, number = {}, pages = {102387}, pmid = {34044101}, issn = {1095-8274}, support = {F32 AI136404/AI/NIAID NIH HHS/United States ; R01 AI139261/AI/NIAID NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/administration &amp; dosage ; Bacteria/classification/genetics/isolation &amp; purification ; Clostridioides difficile/drug effects/genetics/isolation &amp; purification/*physiology ; Clostridium Infections/drug therapy/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces ; Female ; Gastrointestinal Microbiome/drug effects ; Humans ; Microbial Sensitivity Tests ; Polymorphism, Single Nucleotide ; Treatment Failure ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) aims to cure Clostridioides difficile infection (CDI) through reestablishing a healthy microbiome and restoring colonization resistance. Although often effective after one infusion, patients with continued microbiome disruptions may require multiple FMTs. In this N-of-1 study, we use a systems biology approach to evaluate CDI in a patient receiving chronic suppressive antibiotics with four failed FMTs over two years.<br><br>METHODS: Seven stool samples were obtained between 2016-18 while the patient underwent five FMTs. Stool samples were cultured for C.&#xa0;difficile and underwent microbial characterization and functional gene analysis using shotgun metagenomics. C.&#xa0;difficile isolates were characterized through ribotyping, whole genome sequencing, metabolic pathway analysis, and minimum inhibitory concentration (MIC) determinations.<br><br>RESULTS: Growing ten strains from each sample, the index and first four recurrent cultures were single strain ribotype F078-126, the fifth was a mixed culture of ribotypes F002 and F054, and the final culture was ribotype F002. One single nucleotide polymorphism (SNP) variant was identified in the RNA polymerase (RNAP) &#x3b2;-subunit RpoB in the final isolated F078-126 strain when compared to previous F078-126 isolates. This SNV was associated with metabolic shifts but phenotypic differences in fidaxomicin MIC were not observed. Microbiome differences were observed over time during vancomycin therapy and after failed FMTs.<br><br>CONCLUSION: This study highlights the importance of antimicrobial stewardship in patients receiving FMT. Continued antibiotics play a destructive role on a transplanted microbiome and applies selection pressure for resistance to the few antibiotics available to treat CDI.}, }
@article {pmid34043764, year = {2022}, author = {Meedt, E and Hiergeist, A and Gessner, A and Dettmer, K and Liebisch, G and Ghimire, S and Poeck, H and Edinger, M and Wolff, D and Herr, W and Holler, E and Weber, D}, title = {Prolonged Suppression of Butyrate-Producing Bacteria Is Associated With Acute Gastrointestinal Graft-vs-Host Disease and Transplantation-Related Mortality After Allogeneic Stem Cell Transplantation.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {74}, number = {4}, pages = {614-621}, doi = {10.1093/cid/ciab500}, pmid = {34043764}, issn = {1537-6591}, support = {395357507-SFB 1371//Deutsche Forschungsgemeinschaft (German Research Foundation/ ; DJCLS 01 GvHD/2016//German Jos&#xe9; Carreras Leukaemia Foundation/ ; }, mesh = {Bacteria ; Butyrates ; *Graft vs Host Disease/microbiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Transplantation, Homologous/adverse effects ; }, abstract = {BACKGROUND: Butyrogenic bacteria play an important role in gut microbiome homeostasis and intestinal epithelial integrity. Previous studies have demonstrated an association between administration of short-chain fatty acids like butyrate and protection from acute graft-vs-host disease (GvHD) after allogeneic stem cell transplantation (ASCT).<br><br>METHODS: In the current study, we examined the abundance and butyrogenic capacity of butyrate-producing bacteria in 28 healthy donors and 201 patients after ASCT. We prospectively collected serial stool samples and performed polymerase chain reaction analysis of the butyrate-producing bacterial enzyme butyryl-coenzyme A (CoA):acetate CoA-transferase (BCoAT) in fecal nucleic acid extracts.<br><br>RESULTS: Our data demonstrate a strong and prolonged suppression of butyrogenic bacteria early in the course of ASCT. In a multivariable analysis, early use of broad-spectrum antibiotics before day 0 (day of transplantation) was identified as an independent factor associated with low BCoAT copy numbers (odds ratio, 0.370 [95% confidence interval, .175-.783]; P&#x2005;=&#x2005;.009). Diminished butyrogens correlated with other biomarkers of microbial diversity, such as low 3-indoxylsulfate levels, reduced abundance of Clostridiales and low inverse Simpson and effective Shannon indices (all P&#x2005;<&#x2005;.001). Low BCoAT copy numbers at GvHD-onset were correlated with GI-GvHD severity (P&#x2005;=&#x2005;.002) and associated with a significantly higher GvHD-associated mortality rate (P&#x2005;=&#x2005;.04). Furthermore, low BCoAT copy numbers at day 30 were associated with a significantly higher transplantation-related mortality rate (P&#x2005;=&#x2005;.02).<br><br>CONCLUSIONS: Our results are consistent with the hypothesis that alterations in the microbiome play an important role in GvHD pathogenesis and that microbial parameters such as BCoAT might serve as biomarkers to identify patients at high risk of lethal GI-GvHD.}, }
@article {pmid34039493, year = {2021}, author = {Trebicka, J and Macnaughtan, J and Schnabl, B and Shawcross, DL and Bajaj, JS}, title = {The microbiota in cirrhosis and its role in hepatic decompensation.}, journal = {Journal of hepatology}, volume = {75 Suppl 1}, number = {Suppl 1}, pages = {S67-S81}, pmid = {34039493}, issn = {1600-0641}, support = {R21 TR003095/TR/NCATS NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; U01 AA026939/AA/NIAAA NIH HHS/United States ; /DH_/Department of Health/United Kingdom ; I01 CX001076/CX/CSRD VA/United States ; }, mesh = {Acute-On-Chronic Liver Failure/etiology/prevention &amp; control ; Disease Progression ; *Dysbiosis/complications/immunology/physiopathology/therapy ; Gastrointestinal Microbiome/*physiology ; Humans ; *Liver Cirrhosis/complications/microbiology/physiopathology ; }, abstract = {Cirrhosis - the common end-stage of chronic liver disease - is associated with a cascade of events, of which intestinal bacterial overgrowth and dysbiosis are central. Bacterial toxins entering the portal or systemic circulation can directly cause hepatocyte death, while dysbiosis also affects gut barrier function and increases bacterial translocation, leading to infections, systemic inflammation and vasodilation, which contribute to acute decompensation and organ failure. Acute decompensation and its severe forms, pre-acute-on-chronic liver failure (ACLF) and ACLF, are characterised by sudden organ dysfunction (and failure) and high short-term mortality. Patients with pre-ACLF and ACLF present with high-grade systemic inflammation, usually precipitated by proven bacterial infection and/or severe alcoholic hepatitis. However, no precipitant is identified in 30% of these patients, in whom bacterial translocation from the gut microbiota is assumed to be responsible for systemic inflammation and decompensation. Different microbiota profiles may influence the rate of decompensation and thereby outcome in these patients. Thus, targeting the microbiota is a promising strategy for the prevention and treatment of acute decompensation, pre-ACLF and ACLF. Approaches include the use of antibiotics such as rifaximin, faecal microbial transplantation and enterosorbents (e.g. Yaq-001), which bind microbial factors without exerting a direct effect on bacterial growth kinetics. This review focuses on the role of microbiota in decompensation and strategies targeting microbiota to prevent acute decompensation.}, }
@article {pmid34035760, year = {2021}, author = {Allegretti, JR}, title = {Update on Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease.}, journal = {Gastroenterology &amp; hepatology}, volume = {17}, number = {1}, pages = {31-34}, pmid = {34035760}, issn = {1554-7914}, }
@article {pmid34035290, year = {2021}, author = {Malard, F and Vekhoff, A and Lapusan, S and Isnard, F and D'incan-Corda, E and Rey, J and Saillard, C and Thomas, X and Ducastelle-Lepretre, S and Paubelle, E and Larcher, MV and Rocher, C and Recher, C and Tavitian, S and Bertoli, S and Michallet, AS and Gilis, L and Peterlin, P and Chevallier, P and Nguyen, S and Plantamura, E and Boucinha, L and Gasc, C and Michallet, M and Dore, J and Legrand, O and Mohty, M}, title = {Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3084}, pmid = {34035290}, issn = {2041-1723}, mesh = {Acute Disease ; Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bacteria/classification/drug effects/genetics ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Humans ; Leukemia, Myeloid/*drug therapy/microbiology ; Male ; Middle Aged ; Prospective Studies ; Transplantation, Autologous ; Treatment Outcome ; Young Adult ; }, abstract = {Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523). The co-primary outcomes of the study are to evaluate the efficacy of AFMT in dysbiosis correction and multidrug-resistant bacteria eradication. The main secondary outcomes are to define a dysbiosis biosignature, to evaluate the effect of dysbiosis correction on patient clinical status, to assess the short and mid-term safety of AFMT in this immunocompromised population, and to evaluate the feasibility of the AFMT procedure and acceptability by the patient. Intensive induction chemotherapy induces a dramatic decrease of α-diversity indices, and a microbial dysbiosis with a significant shift of the microbial communities and domination of pro-inflammatory families. After AFMT treatment, α-diversity indices return to their initial mean levels and the similarity index shows the restoration of microbial communities. The trial meets pre-specified endpoints. AFMT appears to be safe and may be effective for gut microbiota restoration in AML patients receiving intensive chemotherapy and antibiotics, with an excellent gut microbiota reconstruction based on both richness and diversity indices at the species level.}, }
@article {pmid34030988, year = {2021}, author = {Ianiro, G and Porcari, S and Bibbò, S and Giambò, F and Quaranta, G and Masucci, L and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Donor program for fecal microbiota transplantation: A 3-year experience of a large-volume Italian stool bank.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {53}, number = {11}, pages = {1428-1432}, doi = {10.1016/j.dld.2021.04.009}, pmid = {34030988}, issn = {1878-3562}, mesh = {Adult ; *Biological Specimen Banks/organization &amp; administration/statistics &amp; numerical data ; Donor Selection/*methods/organization &amp; administration/statistics &amp; numerical data ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Infection Control/methods ; Italy ; Male ; Program Evaluation ; Prospective Studies ; }, abstract = {BACKGROUND: Due to the increasing rise of C. difficile infection, stool banks and donor programs have been launched to grant access to fecal microbiota transplantation (FMT). Our aim is to describe characteristics and outcomes of the donor program at our stool bank.<br><br>METHODS: Donor candidates underwent a four-step selection process, including a clinical interview, blood and stool testing, a further questionnaire and a direct stool testing the day of each donation. From March 2020, specific changes to this process were introduced to avoid the potential transmission of COVID-19. We evaluated the rate of excluded candidates at each step of the screening, as well as the number of total fecal aliquots provided by qualified donors.<br><br>RESULTS: Overall, 114 donor candidates were evaluated. Seventy-five candidates declined to join the program for logistic or personal issues, three were excluded after the questionnaire and seven for positive stool exams. Finally, 29 (25%) subjects qualified as stool donors, and provided 70 stool samples. Fifteen samples were excluded after direct molecular stool testing. A total of 127 aliquots was finally obtained.<br><br>CONCLUSIONS: Donor recruitment for FMT is a challenging process, and only a small rate of candidates are eligible as donors.}, }
@article {pmid34030388, year = {2021}, author = {Cheng, W and Wang, Z and Xiong, Y and Wu, Z and Tan, X and Yang, Y and Zhang, H and Zhu, X and Wei, H and Tao, S}, title = {N-(3-oxododecanoyl)-homoserine lactone disrupts intestinal barrier and induces systemic inflammation through perturbing gut microbiome in mice.}, journal = {The Science of the total environment}, volume = {778}, number = {}, pages = {146347}, doi = {10.1016/j.scitotenv.2021.146347}, pmid = {34030388}, issn = {1879-1026}, mesh = {4-Butyrolactone/analogs &amp; derivatives ; Animals ; *Gastrointestinal Microbiome ; Homoserine/analogs &amp; derivatives ; Inflammation ; Mice ; Quorum Sensing ; }, abstract = {As a quorum sensing signal molecule, N-(3-oxododecanoyl)-homoserine lactone (3OC12) regulate the population behavior of microorganisms. Many studies have proved that 3OC12 harm the physiological function of host intestinal epithelial cells. However, the detrimental effects of 3OC12 on intestinal health need verification in animals. Besides, the role of gut microbiome in 3OC12-induced intestinal damage also needs further understanding. In our study, 3OC12 was first administered to specific pathogen-free (SPF) mice, then the fecal microbiome of SPF mice was transplanted into germ-free (GF) mice to reveal the effects of 3OC12 on intestinal health and regulatory mechanisms of the intestinal microbiome. 3OC12 treatment significantly decreased body weight, shortened colonic length, disrupted the morphology of the colonic epithelium and increased the histopathological score of the colon in SPF mice. The levels of diamine peroxidase, d-lactate, TNF-α, IL-1β, and IL-8 were found to be significantly elevated in the serum of 3OC12 mice, while the levels of IL-10 were significantly reduced. Besides, the fecal microbial community of mice was also altered in the 3OC12-treated SPF mice. The results of fecal microbial transplantation (FMT) experiment showed that the phenotypes in SPF mice were almost reproduced in GF mice, manifested by body weight loss, colon damage and changed in serum chemical markers. More importantly, a joint analysis of fecal microbes in SPF and GF mice revealed Feature14_Elizabethkingia spp. was common differential bacteria in the feces of two kinds of mice treated with and without FMT. Our results demonstrated that 3OC12 challenge led to systemic inflammation and body weight loss in mice by disrupting intestinal barrier function, in which gut microbiome played a key role. These findings increased our understanding of the mechanism of intestinal injury caused by 3CO12, providing new ideas for the prevention and therapy of diseases caused by bacterial infection from the perspective of intestinal microbiome.}, }
@article {pmid34030162, year = {2022}, author = {Lemos, MPC and Zucoloto, TG and Oliveira, MC and de Oliveira, GLV}, title = {Dysbiosis and Gut Microbiota Modulation in Systemic Sclerosis.}, journal = {Journal of clinical rheumatology : practical reports on rheumatic &amp; musculoskeletal diseases}, volume = {28}, number = {2}, pages = {e568-e573}, doi = {10.1097/RHU.0000000000001748}, pmid = {34030162}, issn = {1536-7355}, mesh = {Dysbiosis/complications/therapy ; *Gastrointestinal Diseases/diagnosis/etiology/therapy ; *Gastrointestinal Microbiome ; Humans ; *Scleroderma, Systemic/complications/diagnosis/therapy ; }, abstract = {Gastrointestinal (GI) involvement is an early manifestation in systemic sclerosis (SSc), affecting more than 90% of patients, and severe GI disease is a marker of poor prognosis and mortality. Recent studies have hypothesized that alterations of the intestinal microbiota, known as dysbiosis, may represent 1 of the possible environmental factors influencing SSc disease status. In addition, specific microorganisms may be associated with SSc pathogenesis, progression, and GI manifestations. Therapeutic approaches aiming to modulate the intestinal microbiota have emerged, as alternatives to treat GI symptoms, and dietary interventions, probiotic administration, and fecal microbiota transplantation are potential therapies for SSc patients. However, given the complexity and variability of pathogenesis and clinical manifestations in SSc, these therapies need to be combined with additional interventions that target other disease components. Here, we summarize studies addressing intestinal dysbiosis in SSc and discuss the potential of microbiota modulators to treat SSc-related GI disorders.}, }
@article {pmid34029686, year = {2021}, author = {Payne, E and Harrington, K and Richard, P and Brackin, R and Davis, R and Couture, S and Liff, J and Asmus, F and Mutina, E and Fisher, A and Giuvelis, D and Sannajust, S and Rostama, B and King, T and Mattei, LM and Lee, JJ and Friedman, ES and Bittinger, K and May, M and Stevenson, GW}, title = {Effects of Vancomycin on Persistent Pain-Stimulated and Pain-Depressed Behaviors in Female Fischer Rats With or Without Voluntary Access to Running Wheels.}, journal = {The journal of pain}, volume = {22}, number = {11}, pages = {1530-1544}, pmid = {34029686}, issn = {1528-8447}, support = {P20 GM103643/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acids/*drug effects ; Animals ; Anti-Bacterial Agents/*pharmacology ; Behavior, Animal/*drug effects ; Disease Models, Animal ; Female ; Gastrointestinal Microbiome/*drug effects ; Inflammation/complications/*drug therapy ; Motor Activity/*drug effects ; Pain/*drug therapy/etiology ; Rats, Inbred F344 ; Vancomycin/*pharmacology ; Rats ; }, abstract = {The present experiments determined the effects of the narrow-spectrum antibiotic vancomycin on inflammatory pain-stimulated and pain-depressed behaviors in rats. Persistent inflammatory pain was modeled using dilute formalin (0.5%). Two weeks of oral vancomycin administered in drinking water attenuated Phase II formalin pain-stimulated behavior, and prevented formalin pain-depressed wheel running. Fecal microbiota transplantation produced a non-significant trend toward reversal of the vancomycin effect on pain-stimulated behavior. Vancomycin depleted Firmicutes and Bacteroidetes populations in the gut while having a partial sparing effect on Lactobacillus species and Clostridiales. The vancomycin treatment effect was associated with an altered profile in amino acid concentrations in the gut with increases in arginine, glycine, alanine, proline, valine, leucine, and decreases in tyrosine and methionine. These results indicate that vancomycin may have therapeutic effects against persistent inflammatory pain conditions that are distal to the gut. PERSPECTIVE: The narrow-spectrum antibiotic vancomycin reduces pain-related behaviors in the formalin model of inflammatory pain. These data suggest that manipulation of the gut microbiome may be one method to attenuate inflammatory pain amplitude.}, }
@article {pmid34026284, year = {2021}, author = {Liu, L and Wang, H and Rao, X and Yu, Y and Li, W and Zheng, P and Zhao, L and Zhou, C and Pu, J and Yang, D and Fang, L and Ji, P and Song, J and Wei, H and Xie, P}, title = {Comprehensive analysis of the lysine acetylome and succinylome in the hippocampus of gut microbiota-dysbiosis mice.}, journal = {Journal of advanced research}, volume = {30}, number = {}, pages = {27-38}, pmid = {34026284}, issn = {2090-1224}, mesh = {Acetylation ; Animals ; Chromatography, High Pressure Liquid/methods ; Depression/metabolism/microbiology ; Depressive Disorder, Major/*metabolism/microbiology ; Dysbiosis/*metabolism/microbiology ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Gene-Environment Interaction ; Hippocampus/*metabolism ; Humans ; Lysine/*metabolism ; Male ; Mice ; Protein Processing, Post-Translational ; Proteome/*metabolism ; Succinic Acid/metabolism ; Tandem Mass Spectrometry/methods ; }, abstract = {INTRODUCTION: Major depressive disorder is caused by gene-environment interactions, and the host microbiome has been recognized as an important environmental factor. However, the underlying mechanisms of the host-microbiota interactions that lead to depression are complex and remain poorly understood.<br><br>OBJECTIVES: The present study aimed to explore the possible mechanisms underlying gut microbiota dysbiosis-induced depressive-like behaviors.<br><br>METHODS: We used high-performance liquid chromatography-tandem mass spectrometry to analyze alterations in the hippocampal lysine acetylome and succinylome in male mice that had received gut microbiota from fecal samples of either patients with major depressive disorder or healthy controls. This was followed by bioinformatic analyses.<br><br>RESULTS: A total of 315 acetylation sites on 223 proteins and 624 succinylation sites on 494 proteins were differentially expressed in the gut microbiota-dysbiosis mice. The significantly acetylated proteins were primarily associated with carbon metabolism disruption and gene transcription suppression, while the synaptic vesicle cycle and protein translation were the most significantly altered functions for succinylated proteins. Additionally, our findings suggest that gut microbiota dysbiosis disturbs mitochondria-mediated biological processes and the MAPK signaling pathway through crosstalk between acetylation and succinylation on relevant proteins.<br><br>CONCLUSIONS: This is the first study to demonstrate modifications in acetylation and succinylation in gut microbiota-dysbiosis mice. Our findings provide new avenues for exploring the pathogenesis of gut microbiota dysbiosis-related depression, and highlight potential targets for depression treatment.}, }
@article {pmid34025894, year = {2021}, author = {Abrishami, A and Alborzi Avanaki, M and Khalili, N and Taher, M and Ghanaati, H}, title = {Multi-organ infarction following percutaneous transhepatic esophageal variceal obliteration with glue injection: a case report.}, journal = {Radiology case reports}, volume = {16}, number = {7}, pages = {1828-1832}, pmid = {34025894}, issn = {1930-0433}, abstract = {Percutaneous transhepatic variceal obliteration (PTVO) is currently one of the best treatment options for controlling acute recurrent bleeding in cirrhotic patients. Nevertheless, this procedure is associated with major and minor complications such as fever, pain, fatal intraperitoneal hemorrhage, and rarely, embolization of embolic agents to the systemic circulation. Only one study has reported systemic emboli following the use of glue-lipiodal mixture for percutaneous transhepatic embolization of esophageal varices and here we report another case of this complication. Here, we report a 44-year-old man presenting with multi-organ infarction following PTVO with glue-Lipiodol mixture. He was a known case of liver cirrhosis who was admitted for recurrent bleeding from esophageal varices. The patient became a candidate for transjugular intrahepatic portosystemic shunt surgery; however, he did not provide consent for this procedure. the patient eventually decided to undergo PTVO as an alternative option. Twelve hours after the procedure, the patient developed neurological symptoms such as left side weakness, dysarthria, and fecal incontinence. Further investigation showed glue particles in brain, liver, spleen and both lungs. Contrast echocardiography and splenoportography did not show any evidence of right-to-left shunt. Thus, conservative management was initiated for the patient, which resulted in the gradual improvement after three weeks. Prior evaluation with splenoportography and contrast echocardiography before performing PTVO may help in the early detection of any connection with systemic circulation. Also, based on the desired procedure, the most appropriate glue/Lipiodol ratio and injection technique should be selected to minimize the risk of adverse events.}, }
@article {pmid34025607, year = {2021}, author = {Yu, X and Zhou, G and Shao, B and Zhou, H and Xu, C and Yan, F and Wang, L and Chen, G and Li, J and Fu, X}, title = {Gut Microbiota Dysbiosis Induced by Intracerebral Hemorrhage Aggravates Neuroinflammation in Mice.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {647304}, pmid = {34025607}, issn = {1664-302X}, abstract = {Intracerebral hemorrhage (ICH) induces a strong hematoma-related neuroinflammatory reaction and alters peripheral immune homeostasis. Recent research has found that gut microbiota plays a role in neurodegeneration and autoimmune diseases by regulating immune homeostasis and neuroinflammation. Therefore, we investigated the relationship between ICH, microbiota alteration, and immune responses after hematoma-induced acute brain injury. In our study, we used a mouse model of ICH, and 16S ribosomal RNA sequencing showed that ICH causes gut microbiota dysbiosis, which in turn affects ICH outcome through immune-mediated mechanisms. There was prominent reduced species diversity and microbiota overgrowth in the dysbiosis induced by ICH, which may reduce intestinal motility and increase gut permeability. In addition, recolonizing ICH mice with a normal health microbiota ameliorates functional deficits and neuroinflammation after ICH. Meanwhile, cell-tracking studies have demonstrated the migration of intestinal lymphocytes to the brain after ICH. In addition, therapeutic transplantation of fecal microbiota improves intestinal barrier damage. These results support the conclusion that the gut microbiome is a target of ICH-induced systemic alteration and is considered to have a substantial impact on ICH outcome.}, }
@article {pmid34025075, year = {2021}, author = {El-Salhy, M and Casen, C and Valeur, J and Hausken, T and Hatlebakk, JG}, title = {Responses to faecal microbiota transplantation in female and male patients with irritable bowel syndrome.}, journal = {World journal of gastroenterology}, volume = {27}, number = {18}, pages = {2219-2237}, pmid = {34025075}, issn = {2219-2840}, mesh = {Europe ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/diagnosis/therapy ; Male ; Quality of Life ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) seems to be a promising treatment for irritable bowel syndrome (IBS) patients. In Western countries (United States and Europe), there is a female predominance in IBS. A sex difference in the response to FMT has been reported recently in IBS patients.<br><br>AIM: To investigate whether there was a sex difference in the response to FMT in the IBS patients who were included in our previous randomized controlled trial of the efficacy of FMT.<br><br>METHODS: The study included 164 IBS patients who participated in our previous randomized controlled trial. These patients had moderate-to-severe IBS symptoms belonging to the IBS-D (diarrhoea-predominant), IBS-C (constipation-predominant) and IBS-M (mixed) subtypes, and had not responded to the National Institute for Health and Care Excellence (NICE)-modified diet. They belonged in three groups: placebo (own faeces), and active treated group (30-g or 60-g superdonor faeces). The patients completed the IBS severity scoring system (IBS-SSS), Fatigue Assessment Scale (FAS) and the IBS quality of life scale (IBS-QoL) questionnaires at the baseline and 2 wk, 1 mo and 3 mo after FMT. They also provided faecal samples at the baseline and 1 mo after FMT. The faecal bacteria profile and dysbiosis were determined using the 16S rRNA gene polymerase chain reaction DNA amplification covering V3-V9; probe labelling by single nucleotide extension and signal detection. The levels of short-chain fatty acids (SCFAs) were determined by gas chromatography and flame ionization.<br><br>RESULTS: There was no sex difference in the response to FMT either in the placebo group or active treated group. There was no difference between females and males in either the placebo group or actively treated groups in the total score on the IBS-SSS, FAS or IBS-QoL, in dysbiosis, or in the faecal bacteria or SCFA level. However, the response rate was significantly higher in females with diarrhoea-predominant (IBS-D) than that of males at 1 mo, and 3 mo after FMT. Moreover, IBS-SSS total score was significantly lower in female patients with IBS-D than that of male patients both 1 mo and 3 mo after FMT.<br><br>CONCLUSION: There was no sex difference in the response to FMT among IBS patients with moderate-to-severe symptoms who had previously not responded to NICE-modified diet. However, female patients with IBS-D respond better and have higher reduction of symptoms than males after FMT.}, }
@article {pmid34022075, year = {2021}, author = {Ni, Z and Ding, J and Zhao, Q and Cheng, W and Yu, J and Zhou, L and Sun, S and Yu, C}, title = {Alpha-linolenic acid regulates the gut microbiota and the inflammatory environment in a mouse model of endometriosis.}, journal = {American journal of reproductive immunology (New York, N.Y. : 1989)}, volume = {86}, number = {4}, pages = {e13471}, doi = {10.1111/aji.13471}, pmid = {34022075}, issn = {1600-0897}, mesh = {Animals ; Disease Models, Animal ; Endometriosis/*metabolism ; Female ; Gastrointestinal Microbiome/*drug effects ; Mice ; Zonula Occludens-2 Protein/metabolism ; alpha-Linolenic Acid/*pharmacology ; }, abstract = {PROBLEM: This study aims to investigate the effects of alpha-linolenic acid (ALA) on the gut microbiota (GM) and the abdominal environment in mice with endometriosis (EMS).<br><br>METHODS: The effects of faecal microbiota transplantation (FMT) from EMS mice on mice treated with antibiotic cocktail were conducted. The 16S rRNA sequencing and PICRUSt software were used to detect the structure and function of GM respectively. The protein levels of Claudin 4 and ZO-2 in the intestinal wall were detected using the western blotting. The level of LPS in the abdominal cavity was detected using enzyme-linked immunosorbent assay (ELISA). The content of macrophages in the abdominal cavity was detected using flow cytometry.<br><br>RESULTS: The exogenous supplementation of ALA could restore the abundance of Firmicutes and Bacteroidota in EMS mice. After the ALA treatment, the abundance of 125 functional pathways and 50 abnormal enzymes related to GM in EMS mice was significantly improved (p&#xa0;<&#xa0;.05). The expression of the ZO-2 protein in the intestinal wall was decreased, and the level of LPS in the abdominal cavity was significantly increased after FMT from EMS mice (p&#xa0;<&#xa0;.05). ALA could increase the expression of the ZO-2 protein in the intestinal wall of EMS mice, reduce the level of LPS in the abdominal cavity (p&#xa0;<&#xa0;.05) and reduce the aggregation of peritoneal macrophages (p&#xa0;<&#xa0;.05).<br><br>CONCLUSION: Alpha-linolenic acid can improve the GM, intestinal wall barrier and abdominal inflammatory environment and reduce the level of LPS in mice with EMS.}, }
@article {pmid34020027, year = {2022}, author = {Saeed, M and Shoaib, A and Kandimalla, R and Javed, S and Almatroudi, A and Gupta, R and Aqil, F}, title = {Microbe-based therapies for colorectal cancer: Advantages and limitations.}, journal = {Seminars in cancer biology}, volume = {86}, number = {Pt 3}, pages = {652-665}, doi = {10.1016/j.semcancer.2021.05.018}, pmid = {34020027}, issn = {1096-3650}, mesh = {Male ; Humans ; Female ; *Colorectal Neoplasms/etiology/therapy/metabolism ; *Gastrointestinal Microbiome ; Prebiotics ; *Probiotics/therapeutic use ; *Microbiota ; }, abstract = {Cancer is one of the leading global causes of death in both men and women. Colorectal cancer (CRC) alone accounts for ∼10 % of total new global cases and poses an over 4% lifetime risk of developing cancer. Recent advancements in the field of biotechnology and microbiology concocted novel microbe-based therapies to treat various cancers, including CRC. Microbes have been explored for human use since centuries, especially for the treatment of various ailments. The utility of microbes in cancer therapeutics is widely explored, and various bacteria, fungi, and viruses are currently in use for the development of cancer therapeutics. The human gut hosts about 100 trillion microbes that release their metabolites in active, inactive, or dead conditions. Microbial secondary metabolites, proteins, immunotoxins, and enzymes are used to target cancer cells to induce cell cycle arrest, apoptosis, and death. Various approaches, such as dietary interventions, the use of prebiotics and probiotics, and fecal microbiota transplantation have been used to modulate the gut microbiota in order to prevent or treat CRC pathogenesis. The present review highlights the role of the gut microbiota in CRC precipitation, the potential mechanisms and use of microorganisms as CRC biomarkers, and strategies to modulate microbiota for the prevention and treatment of CRC.}, }
@article {pmid34019628, year = {2021}, author = {Ni, H and Chen, Y and Xia, W and Wang, C and Hu, C and Sun, L and Tang, W and Cui, H and Shen, T and Liu, Y and Li, J}, title = {SATB2 Defect Promotes Colitis and Colitis-associated Colorectal Cancer by Impairing Cl-/HCO3- Exchange and Homeostasis of Gut Microbiota.}, journal = {Journal of Crohn's &amp; colitis}, volume = {15}, number = {12}, pages = {2088-2102}, doi = {10.1093/ecco-jcc/jjab094}, pmid = {34019628}, issn = {1876-4479}, support = {81972259//National Natural Science Foundation of China/ ; 81525020//National Science Fund for Distinguished Young Scholars/ ; 2020M683071//China Postdoctoral Science Foundation/ ; XKTJ-JD202006//Second Affiliated Hospital of Soochow University/ ; //Jiangsu Higher Education Institutions/ ; }, mesh = {Animals ; Biomarkers/metabolism ; Cell Line, Tumor ; Chloride-Bicarbonate Antiporters/*metabolism ; Colitis, Ulcerative/*complications ; Colorectal Neoplasms/complications/*genetics ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Humans ; Matrix Attachment Region Binding Proteins/*metabolism ; Mice ; Mice, Knockout ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: SATB2 is a diagnostic biomarker and a favourable prognostic marker for colorectal cancer [CRC], but its role in colitis and colitis-associated colorectal cancer [CAC] is unknown.<br><br>METHODS: Colitis was induced in intestinal epithelial-specific Satb2 knockout [Satb2 IEC-KO] and control mice using dextran sulphate sodium [DSS]. RNA-seq analysis was performed on colonic tissues, and 16S rDNA-Seq on faecal bacterial DNA from Satb2 IEC-KO and control mice. Immunohistochemistry and flow cytometry were performed to reveal the proportions of different immune cells. Chromatin immunoprecipitation [ChIP] and luciferase reporter were applied to show the regulatory role of SATB2 on SLC26A3, of which the Cl-/HCO3- exchange activity was measured fluorometrically by the pHi-sensitive dye. Bacteroides were detected by fluorescence in situ hybridisation [FISH] on colonic tissue.<br><br>RESULTS: Satb2 IEC-KO mice suffered from intestinal epithelial damage spontaneously, and developed more severe colitis and CAC. The expression of SLC26A3 correlated well with SATB2 revealed by RNA-seq and The Cancer Genome Atlas [TCGA] data, and was governed by SATB2 confirmed by ChIP and luciferase reporter experiments. Decreased intestinal flora diversity was seen in Satb2 IEC-KO mice. Bacteroides were more abundant and could colonise into the inner layer of colonic mucosa in Satb2 IEC-KO mice. Faecal microbiome transplantation from Satb2 IEC-KO mice aggravated colitis and M1 macrophages infiltration.<br><br>CONCLUSIONS: SATB2 plays a vital role in maintaining intestinal homeostasis, and its deficiency promotes the development of colitis and CAC by influencing the intestinal luminal environment and gut flora.}, }
@article {pmid34018696, year = {2021}, author = {Lu, C and Tang, S and Han, J and Fan, S and Huang, Y and Zhang, Z and Zhou, J and Ming, T and Li, Y and Su, X}, title = {Apostichopus japonicus Oligopeptide Induced Heterogeneity in the Gastrointestinal Tract Microbiota and Alleviated Hyperuricemia in a Microbiota-Dependent Manner.}, journal = {Molecular nutrition &amp; food research}, volume = {65}, number = {14}, pages = {e2100147}, doi = {10.1002/mnfr.202100147}, pmid = {34018696}, issn = {1613-4133}, mesh = {Animals ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Hyperuricemia/*drug therapy ; Male ; Mice ; Mice, Inbred ICR ; NF-kappa B/metabolism ; Oligopeptides/*pharmacology ; Plant Preparations/*pharmacology ; Signal Transduction/drug effects ; Stichopus/*chemistry ; Uric Acid/metabolism ; }, abstract = {SCOPE: This study aims to investigate the protective effect of Apostichopus japonicus oligopeptide (AJOP) on hyperuricemia, demonstrate the modulation of the gastrointestinal tract (GIT) microbiota, and clarify the underlying microbiota-dependent mechanism.<br><br>METHODS AND RESULTS: Hyperuricemic mice treated with AJOP and subjected to corresponding fecal microbiota transplantation (FMT) are used to observe the beneficial effects of AJOP and microbiota. Gene transcriptions are measured using quantitative real-time PCR. The GIT (stomach, colon, cecum, and feces) microbiota is analyzed by 16S rDNA sequencing and the short-chain fatty acids are detected using GC-MS. Dietary administration of AJOP significantly alleviates hyperuricemia, regulates uric acid metabolism, inhibites the activation of the NLRP3 inflammasome and NF-&#x3ba;B-related signaling pathway, and restores m6A methylation levels. In addition, substantial heterogeneity is observed in GIT microbiota. Furthermore, FMT effectively alleviates hyperuricemia in mice by selectively regulating the corresponding pathways associated with AJOP treatment, indicating that the mechanism underlying the protective effects of AJOP is partly microbiota-dependent.<br><br>CONCLUSION: This study demonstrates that AJOP exerts a protective effect on hyperuricemic mice by regulating uric acid metabolism, resulting in substantial heterogeneity among the GIT microbiota, thus mediating the beneficial effects in a microbiota-dependent manner.}, }
@article {pmid34017186, year = {2021}, author = {Wang, J and Li, X and Wu, X and Wang, Z and Wu, X and Wang, S and Jing, G and Yan, T}, title = {Fecal Microbiota Transplantation as an Effective Treatment for Carbapenem-Resistant Klebsiella pneumoniae Infection in a Renal Transplant Patient.}, journal = {Infection and drug resistance}, volume = {14}, number = {}, pages = {1805-1811}, pmid = {34017186}, issn = {1178-6973}, abstract = {BACKGROUND: In renal transplant recipients, carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a common complication, and usually associated with severe clinical outcomes due to a lack of effective treatment.<br><br>CASE PRESENTATION: A 37-year-old woman with CRKP infection one month after kidney transplantation was involved in this study. Microbial characteristics of fecal samples from the patient were analyzed. Fecal microbiota transplantation (FMT) was performed for treating the CRKP infection. One week after FMT, the patient's urine and anal swab cultures returned negative for CRKP, and 17 days after FMT, the incision showed complete healing. Moreover, the patient had no symptoms of infection two months after FMT. Alpha diversity analyses showed that before FMT, the patient was associated with obviously lower species richness and diversity than the donor, which significantly increased at one week, three weeks and two months after FMT. Beta diversity analyses showed that though the patient's microbial community post-FMT still differed from the donor composition, their distances decreased visibly, especially at one week and three weeks after FMT. Obvious shift in microbial composition could be observed before and after FMT. The microbial composition of the patient post FMT resembled the donor composition. Relative abundance of genera such as Phascolarctobacterium and Lachnoclostridium increased after FMT, while the relative abundance of Klebsiella significantly decreased.<br><br>CONCLUSION: This study demonstrated the therapeutic effect of FMT on infections caused by CRKP for a renal transplant patient. Further studies are required to confirm the findings of this study.}, }
@article {pmid34017107, year = {2021}, author = {Liu, Y and Yang, K and Jia, Y and Shi, J and Tong, Z and Fang, D and Yang, B and Su, C and Li, R and Xiao, X and Wang, Z}, title = {Gut microbiome alterations in high-fat-diet-fed mice are associated with antibiotic tolerance.}, journal = {Nature microbiology}, volume = {6}, number = {7}, pages = {874-884}, pmid = {34017107}, issn = {2058-5276}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Bacterial Infections/drug therapy/metabolism/microbiology ; Bacterial Load/drug effects ; Diet, High-Fat/*adverse effects ; Disease Models, Animal ; Escherichia coli/drug effects/metabolism ; Gastrointestinal Microbiome/*drug effects ; Indoleacetic Acids/metabolism/pharmacology ; Methicillin-Resistant Staphylococcus aureus/drug effects/metabolism ; Mice ; Obesity/metabolism/microbiology ; }, abstract = {Antibiotic tolerance, the ability of a typically susceptible microorganism to survive extended periods of exposure to antibiotics, has a critical role in chronic and recurrent bacterial infections, and facilitates the evolution of antibiotic resistance. However, the physiological factors that contribute to the development of antibiotic tolerance, particularly in vivo, are not fully known. Despite the fact that a high-fat diet (HFD) is implicated in several human diseases, the relationship between HFD and antibiotic efficacy is still poorly understood. Here, we evaluated the efficacy of multiple clinically relevant bactericidal antibiotics in HFD-fed mice infected with methicillin-resistant Staphylococcus aureus (MRSA) or Escherichia coli. We found that HFD-fed mice had higher bacterial burdens and these bacteria displayed lower susceptibility to bactericidal antibiotic treatment compared with mice that were fed a standard diet, while microbiota-depleted standard-diet- or HFD-fed mice showed similar susceptibility. Faecal microbiota transplantation from HFD-fed mice impaired antibiotic activity in mice fed a standard diet, indicating that alteration of the gut microbiota and related metabolites in HFD-fed mice may account for the decreased antibiotic activity. 16S rRNA sequencing and metabolomics analysis of faecal samples revealed decreased microbial diversity and differential metabolite profiles in HFD-fed mice. Notably, the tryptophan metabolite indole-3-acetic acid (IAA) was significantly decreased in HFD-fed mice. Further in vitro studies showed that IAA supplementation inhibited the formation of bacterial persisters and promoted the elimination of persisters in combination with antibiotic treatment, potentially through the activation of bacterial metabolic pathways. In vivo, the combination of IAA and ciprofloxacin increased the survival rate of HFD-fed mice infected with MRSA persisters. Overall, our data reveal that a HFD has an antagonistic effect on antibiotic treatment in a mouse model, and this is associated with the alteration of the gut microbiota and IAA production.}, }
@article {pmid34017060, year = {2021}, author = {Kim, JH and Kim, K and Kim, W}, title = {Gut microbiota restoration through fecal microbiota transplantation: a new atopic dermatitis therapy.}, journal = {Experimental &amp; molecular medicine}, volume = {53}, number = {5}, pages = {907-916}, pmid = {34017060}, issn = {2092-6413}, mesh = {Animals ; Antibodies/pharmacology ; Biomarkers ; Dermatitis, Atopic/etiology/*therapy ; Disease Management ; Disease Models, Animal ; Disease Susceptibility ; Fatty Acids, Volatile/metabolism ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/drug effects/immunology ; Immunoglobulin E/blood/immunology ; Immunomodulation ; Lymphocyte Count ; Metagenome ; Metagenomics ; Mice ; T-Lymphocyte Subsets/immunology/metabolism ; Treatment Outcome ; }, abstract = {The pathogenesis of atopic dermatitis (AD) involves complex factors, including gut microbiota and immune modulation, which remain poorly understood. The aim of this study was to restore gut microbiota via fecal microbiota transplantation (FMT) to ameliorate AD in mice. FMT was performed using stool from donor mice. The gut microbiota was characterized via 16S rRNA sequencing and analyzed using Quantitative Insights into Microbial Ecology 2 with the DADA2 plugin. Gut metabolite levels were determined by measuring fecal short-chain fatty acid (SCFA) contents. AD-induced allergic responses were evaluated by analyzing blood parameters (IgE levels and eosinophil percentage, eosinophil count, basophil percentage, and monocyte percentage), the levels of Th1 and Th2 cytokines, dermatitis score, and the number of mast cells in the ileum and skin tissues. Calprotectin level was measured to assess gut inflammation after FMT. FMT resulted in the restoration of gut microbiota to the donor state and increases in the levels of SCFAs as gut metabolites. In addition, FMT restored the Th1/Th2 balance, modulated Tregs through gut microbiota, and reduced IgE levels and the numbers of mast cells, eosinophils, and basophils. FMT is associated with restoration of gut microbiota and immunologic balance (Th1/Th2) along with suppression of AD-induced allergic responses and is thus a potential new therapy for AD.}, }
@article {pmid34016825, year = {2021}, author = {Ascanelli, S and Zamboni, P and Campioni, D and Grazia Sibilla, M and Chimisso, L and Zollino, I and Valpiani, G and Carcoforo, P}, title = {Efficacy and Safety of Treatment of Complex Idiopathic Fistula-in-Ano Using Autologous Centrifuged Adipose Tissue Containing Progenitor Cells: A Randomized Controlled Trial.}, journal = {Diseases of the colon and rectum}, volume = {64}, number = {10}, pages = {1276-1285}, doi = {10.1097/DCR.0000000000001924}, pmid = {34016825}, issn = {1530-0358}, mesh = {Adipose Tissue/*cytology ; Case-Control Studies ; Fecal Incontinence/epidemiology ; Female ; Humans ; Injections, Subcutaneous/methods ; Italy/epidemiology ; Magnetic Resonance Imaging/methods ; Male ; Mesenchymal Stem Cell Transplantation/*adverse effects/methods ; Mesenchymal Stem Cells ; Middle Aged ; Pain, Postoperative/epidemiology ; Patient Satisfaction/statistics &amp; numerical data ; Pelvis/diagnostic imaging ; Rectal Fistula/pathology/*therapy ; Return to Work/statistics &amp; numerical data ; Safety ; Treatment Outcome ; Wound Healing/*physiology ; }, abstract = {BACKGROUND: Mesenchymal stem cells derived from adipose tissue have been successfully used to promote sphincter-saving anal fistula healing.<br><br>OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of the use of autologous centrifuged adipose tissue in the healing process of cryptoglandular complex anal fistulas.<br><br>DESIGN: This is a randomized controlled trial.<br><br>SETTINGS: This study was conducted at a single center.<br><br>PATIENTS: Patients with complex perianal fistulas not associated with Crohn's disease were included. Rectovaginal fistulas were not included.<br><br>INTERVENTIONS: Patients were randomly allocated to receive treatment with centrifuged adipose tissue injection (experimental group) and without injection (control group) in combination with fistula surgery.<br><br>MAIN OUTCOME MEASURES: The primary outcome was defined as the proportion of patients with complete fistula closure at 4 weeks (short-term outcome) and 6 months after surgery (long-term outcome). Healing was defined as when the external opening was closed with no perianal discharge on clinical assessment. The secondary outcome was safety that was evaluated by the analysis of adverse events up to 3 months after surgery. Pelvic MRI was performed at 3 months to assure safety and the accuracy of the clinical determination of healing. Postoperative pain, return to work/daily activities, persistent closure at 6 months, fecal incontinence, and patient satisfaction were evaluated.<br><br>RESULTS: Fifty-eight patients who received centrifuged adipose tissue injection and 58 patients who did not receive centrifuged adipose tissue injection were included in the safety and efficacy analysis. After 4 weeks, the healing rate was 63.8% in the experimental group compared with 15.5% in the control group (p < 0.001). No major adverse events were recorded. Postoperative anal pain was significantly lower in the injection group. Time taken to return to work/daily activities was significantly shorter in the experimental group (3 days) than in the control group (17 days). At 6 months, persistent closure was similar in the 2 groups (86.2% vs 81%). Fecal Incontinence Score at 6 months after surgery was identical to the preoperative score. Patient satisfaction was high in both groups.<br><br>LIMITATIONS: The absence of blinding, the lack of correlation between stem cell content, and the clinical outcome were limitations of the study.<br><br>CONCLUSIONS: Autologous centrifuged adipose tissue injection may represent a safe, efficacious, and inexpensive option for the treatment of complex fistula-in-ano. See Video Abstract at http://links.lww.com/DCR/B607.<br><br>CLINICAL TRIALS REGISTRATION: URL: https://www.clinicaltrials.gov. Identifier: NCT04326907.<br><br>ANTECEDENTES:Las c&#xe9;lulas madre mesenquimales derivadas del tejido adiposo se han utilizado con &#xe9;xito para promover la curaci&#xf3;n de la f&#xed;stula anal con preservaci&#xf3;n de esf&#xed;nter.OBJETIVO:El objetivo de este estudio fue evaluar la eficacia y seguridad del uso de tejido adiposo aut&#xf3;logo centrifugado en el proceso de cicatrizaci&#xf3;n de f&#xed;stulas anales complejas de origen criptoglandular.DISE&#xd1;O:Ensayo controlado aleatorio.ENTORNO CL&#xcd;NICO:Estudio unic&#xe9;ntrico.PACIENTES:Se incluyeron pacientes con f&#xed;stulas perianales complejas no asociadas a Enfermedad de Crohn. No se incluyeron las f&#xed;stulas rectovaginales.INTERVENCIONES:Los pacientes fueron asignados aleatoriamente para recibir tratamiento con inyecci&#xf3;n de tejido adiposo centrifugado (grupo experimental) y sin inyecci&#xf3;n (grupo de control) en combinaci&#xf3;n con cirug&#xed;a de f&#xed;stula.PRINCIPALES MEDIDAS DE VALORACI&#xd3;N:El resultado primario se defini&#xf3; como la proporci&#xf3;n de pacientes con cierre completo de la f&#xed;stula a las 4 semanas (resultado a corto plazo) y 6 meses despu&#xe9;s de la cirug&#xed;a (resultado a largo plazo). La curaci&#xf3;n se defini&#xf3; cuando orificio externo se cerr&#xf3; sin secreci&#xf3;n perianal en la valoraci&#xf3;n cl&#xed;nica. El resultado secundario fue la seguridad que se evalu&#xf3; mediante el an&#xe1;lisis de los eventos adversos (EA) hasta 3 meses despu&#xe9;s de la cirug&#xed;a. La resonancia magn&#xe9;tica p&#xe9;lvica se realiz&#xf3; a los 3 meses para garantizar la seguridad y la precisi&#xf3;n cl&#xed;nica de la curaci&#xf3;n. Se evalu&#xf3; el dolor postoperatorio, el regreso al trabajo / actividades diarias, el cierre persistente a los 6 meses, la incontinencia fecal y la satisfacci&#xf3;n del paciente.RESULTADOS:Cincuenta y ocho pacientes que recibieron inyecci&#xf3;n de tejido adiposo centrifugado y 58 pacientes que no recibieron inyecci&#xf3;n de tejido adiposo centrifugado se incluyeron en el an&#xe1;lisis de seguridad y eficacia. Despu&#xe9;s de 4 semanas, la tasa de curaci&#xf3;n fue del 63,8% en el grupo experimental en comparaci&#xf3;n con el 15,5% en el grupo de control (p <0,001). No se registraron eventos adversos importantes. El dolor anal posoperatorio fue significativamente menor en el grupo de inyecci&#xf3;n. El tiempo necesario para volver al trabajo / actividades diarias fue significativamente menor en el grupo experimental (3 d&#xed;as) con respecto al grupo de control (17 d&#xed;as). A los 6 meses, el cierre persistente fue similar en los dos grupos (86,2% vs 81%). La puntuaci&#xf3;n de incontinencia fecal a los 6 meses despu&#xe9;s de la cirug&#xed;a fue id&#xe9;ntica a la puntuaci&#xf3;n preoperatoria. La satisfacci&#xf3;n del paciente fue muy alta en ambos grupos.LIMITACIONES:Ausencia de cegamiento, falta de correlaci&#xf3;n entre el contenido de c&#xe9;lulas madre y el resultado cl&#xed;nico.CONCLUSIONES:La inyecci&#xf3;n de tejido adiposo centrifugado aut&#xf3;logo puede representar una opci&#xf3;n segura, eficaz y econ&#xf3;mica para el tratamiento de la f&#xed;stula anal compleja.Registro de ensayos cl&#xed;nicos: www.clinicaltrials.gov, identificador NCT04326907; No patrocinado.Consulte Video Resumen en http://links.lww.com/DCR/B607.}, }
@article {pmid34016163, year = {2021}, author = {Lei, Y and Tang, L and Liu, S and Hu, S and Wu, L and Liu, Y and Yang, M and Huang, S and Tang, X and Tang, T and Zhao, X and Vlodavsky, I and Zeng, S and Tang, B and Yang, S}, title = {Parabacteroides produces acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {115}, pmid = {34016163}, issn = {2049-2618}, support = {81661148050//National Natural Science Foundation of China/ ; 81972327//National Natural Science Foundation of China/ ; }, mesh = {*Acetates ; Acute Disease ; Animals ; *Bacteroides ; *Gastrointestinal Microbiome ; Glucuronidase ; Mice ; Mice, Transgenic ; *Neutrophil Infiltration ; Pancreatitis/*microbiology ; }, abstract = {BACKGROUND: The endoglycosidase heparanase which degrades heparan sulfate proteoglycans, exerts a pro-inflammatory mediator in various inflammatory disorders. However, the function and underlying mechanism of heparanase in acute pancreatitis remain poorly understood. Here, we investigated the interplay between heparanase and the gut microbiota in the development of acute pancreatitis.<br><br>METHODS: Acute pancreatitis was induced in wild-type and heparanase-transgenic mice by administration of caerulein. The differences in gut microbiota were analyzed by 16S ribosomal RNA sequencing. Antibiotic cocktail experiment, fecal microbiota transplantation, and cohousing experiments were used to assess the role of gut microbiota.<br><br>RESULTS: As compared with wild-type mice, acute pancreatitis was exacerbated in heparanase-transgenic mice. Moreover, the gut microbiota differed between heparanase-transgenic and wild-type mice. Heparanase exacerbated acute pancreatitis in a gut microbiota-dependent manner. Specially, the commensal Parabacteroides contributed most to distinguish the differences between wild-type and heparanase-transgenic mice. Administration of Parabacteroides alleviated acute pancreatitis in wild-type and heparanase-transgenic mice. In addition, Parabacteroides produced acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration.<br><br>CONCLUSIONS: The gut-pancreas axis played an important role in the development of acute pancreatitis and the acetate produced by Parabacteroides may be beneficial for acute pancreatitis treatment. Video abstract.}, }
@article {pmid34015282, year = {2021}, author = {Dixit, K and Chaudhari, D and Dhotre, D and Shouche, Y and Saroj, S}, title = {Restoration of dysbiotic human gut microbiome for homeostasis.}, journal = {Life sciences}, volume = {278}, number = {}, pages = {119622}, doi = {10.1016/j.lfs.2021.119622}, pmid = {34015282}, issn = {1879-0631}, mesh = {Animals ; Dysbiosis/microbiology/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Homeostasis ; Humans ; Immunomodulation ; Microbiota ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The human microbiome is a complex and dynamic ecosystem, and the imbalance of its microbial community structure from the normal state is termed dysbiosis. The dysbiotic gut microbiome has been proved to be related to several pathological conditions like Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), Colorectal Cancer (CRC), etc., and several other extra-intestinal conditions like Type 1 &amp; 2 diabetes, obesity, etc. The complex gut microbial ecosystem starts to build before the birth of an individual. It is known to get affected by several factors such as birth mode, individual lifestyle, dietary practices, medications, and antibiotics. A dysbiotic microbiome can potentially hamper host homeostasis due to its role in immune modulation, metabolism, nutrient synthesis, etc. Restoration of the dysbiotic gut microbiome has emerged as a promising aid and a better therapeutic approach. Several approaches have been investigated to achieve this goal, including prebiotics and probiotics, Fecal Microbiota Transplantation (FMT), extracellular vesicles, immune modulation, microbial metabolites, dietary interventions, and phages. This review discusses the various factors that influence the human microbiome with respect to their cause-effect relationship and the effect of gut microbiome compositional changes on the brain through the gut-brain axis. We also discuss the practices used globally for gut microbiome restoration purposes, along with their effectiveness.}, }
@article {pmid34006584, year = {2022}, author = {Huang, J and Liu, D and Wang, Y and Liu, L and Li, J and Yuan, J and Jiang, Z and Jiang, Z and Hsiao, WW and Liu, H and Khan, I and Xie, Y and Wu, J and Xie, Y and Zhang, Y and Fu, Y and Liao, J and Wang, W and Lai, H and Shi, A and Cai, J and Luo, L and Li, R and Yao, X and Fan, X and Wu, Q and Liu, Z and Yan, P and Lu, J and Yang, M and Wang, L and Cao, Y and Wei, H and Leung, EL}, title = {Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy.}, journal = {Gut}, volume = {71}, number = {4}, pages = {734-745}, pmid = {34006584}, issn = {1468-3288}, mesh = {Animals ; Antibodies, Monoclonal/pharmacology ; Apoptosis ; B7-H1 Antigen/metabolism ; *Carcinoma, Non-Small-Cell Lung/therapy ; Cell Death ; *Gastrointestinal Microbiome/physiology ; Humans ; Immunologic Factors/pharmacology ; Immunotherapy/methods ; Kynurenine/pharmacology ; Ligands ; *Lung Neoplasms/therapy ; Mice ; *Panax/metabolism ; Polysaccharides/pharmacology ; Tryptophan/pharmacology ; }, abstract = {OBJECTIVE: Programmed death 1 and its ligand 1 (PD-1/PD-L1) immunotherapy is promising for late-stage lung cancer treatment, however, the response rate needs to be improved. Gut microbiota plays a crucial role in immunotherapy sensitisation and Panax ginseng has been shown to possess immunomodulatory potential. In this study, we aimed to investigate whether the combination treatment of ginseng polysaccharides (GPs) and αPD-1 monoclonal antibody (mAb) could sensitise the response by modulating gut microbiota.<br><br>DESIGN: Syngeneic mouse models were administered GPs and &#x3b1;PD-1 mAb, the sensitising antitumour effects of the combination therapy on gut microbiota were assessed by faecal microbiota transplantation (FMT) and 16S PacBio single-molecule real-time (SMRT) sequencing. To assess the immune-related metabolites, metabolomics analysis of the plasma samples was performed.<br><br>RESULTS: We found GPs increased the antitumour response to &#x3b1;PD-1 mAb by increasing the microbial metabolites valeric acid and decreasing L-kynurenine, as well as the ratio of Kyn/Trp, which contributed to the suppression of regulatory T cells and induction of Teff cells after combination treatment. Besides, the microbial analysis indicated that the abundance of Parabacteroides distasonis and Bacteroides vulgatus was higher in responders to anti-PD-1 blockade than non-responders in the clinic. Furthermore, the combination therapy sensitised the response to PD-1 inhibitor in the mice receiving microbes by FMT from six non-responders by reshaping the gut microbiota from non-responders towards that of responders.<br><br>CONCLUSION: Our results demonstrate that GPs combined with &#x3b1;PD-1 mAb may be a new strategy to sensitise non-small cell lung cancer patients to anti-PD-1 immunotherapy. The gut microbiota can be used as a novel biomarker to predict the response to anti-PD-1 immunotherapy.}, }
@article {pmid34006020, year = {2021}, author = {Kragsnaes, MS and Sødergren, ST and Kjeldsen, J and Horn, HC and Munk, HL and Pedersen, JK and Klinkby, CS and de Wit, M and Ahlmark, NG and Tjørnhøj-Thomsen, T and Ellingsen, T}, title = {Experiences and perceptions of patients with psoriatic arthritis participating in a trial of faecal microbiota transplantation: a nested qualitative study.}, journal = {BMJ open}, volume = {11}, number = {3}, pages = {e039471}, pmid = {34006020}, issn = {2044-6055}, mesh = {*Antirheumatic Agents ; *Arthritis, Psoriatic/therapy ; Double-Blind Method ; Fecal Microbiota Transplantation ; Humans ; Perception ; }, abstract = {OBJECTIVES: Patients' first-hand experiences of faecal microbiota transplantation (FMT) performed in a rheumatological care setting have yet to be elucidated. The objectives were to explore participants' perceptions of being part of an FMT trial thereby identifying potential trial participation effects and enlightening the patient perspective on the outlook for future FMT trials in rheumatic diseases.<br><br>DESIGN: In a qualitative study nested within a double-blind, randomised, placebo-controlled trial (RCT) testing FMT as a potential new antirheumatic treatment, semistructured telephone interviews were conducted following the trial participants' final 26-week visit. Qualitative researchers, who did not take part in the main trial, performed the interviews and the primary analysis. The experiences explored related to the conduct of the RCT and changes in the participants' everyday life. The analysis was carried out using a thematic approach.<br><br>SETTING: A Danish rheumatology university outpatient clinic with nationwide inclusion.<br><br>PARTICIPANTS: The study included 10 patients with psoriatic arthritis (PsA) who were unaware of their treatment allocation (FMT/sham transplantation) and completed the final 26-week trial visit.<br><br>RESULTS: Participation in the RCT influenced the patients' understanding of PsA and induced positive changes in their everyday life. Renewed hopes for the future in addition to a feeling of enhanced care contributed to significant trial participation effects. FMT was deemed a tolerable and safe treatment.<br><br>CONCLUSIONS: Discrepancies between the clinical and the research setting should be considered when discussing the clinical relevance of the results of the RCT. Overall, patients with PsA who have participated in an RCT testing FMT find the treatment acceptable and safe encouraging more research into the field of microbiota-targeted interventions in rheumatic diseases.<br><br>TRIAL REGISTRATION NUMBER: NCT03058900; Pre-results.}, }
@article {pmid34004414, year = {2021}, author = {Feng, D and Chen, B and Zeng, B and Xiao, L and Yan, J and Yang, T and Zhu, J and Li, T and Wang, L and Wei, H and Chen, J}, title = {Fecal microbiota from children with vitamin A deficiency impair colonic barrier function in germ-free mice: The possible role of alterative bile acid metabolites.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {90}, number = {}, pages = {111274}, doi = {10.1016/j.nut.2021.111274}, pmid = {34004414}, issn = {1873-1244}, mesh = {Animals ; Bile Acids and Salts ; Colon ; Feces ; *Gastrointestinal Microbiome ; Mice ; *Vitamin A Deficiency ; }, abstract = {OBJECTIVE: This study explores the effects of fecal microbiota from children with vitamin A (VA) deficiency on colonic mucosal barrier function.<br><br>METHODS: The composition of gut microbes was identified in children with different VA levels, then feces from children with normal VA or VA deficiency was collected separately and transplanted into germ-free (GF) mice, respectively. Three weeks after transplantation, the colon morphology, colonic tight junction proteins, gut microbes, and metabolites were evaluated.<br><br>RESULTS: In children, Bifidobacterium and Bacteroides were positively correlated with VA levels. Colonization of VA deficiency fecal microbiota markedly impaired colonic development in GF mice, down-regulated colonic tight junction-related proteins occludin and claudin-1, and reduced immunoglobulin A secretion. Furthermore, fecal microbiota transplantation with different VA levels altered composition of gut microbes and bile acid metabolism pathways in GF mice.<br><br>CONCLUSION: These data suggest that fecal microbiota from children with VA deficiency attenuates colonic barrier function in GF mice, which may be achieved by changing the bile acid metabolic pathways.}, }
@article {pmid34003771, year = {2021}, author = {Sharma, D}, title = {Towards Taming the Bugs to Improve the Drugs for Breast Cancer.}, journal = {Cancer research}, volume = {81}, number = {8}, pages = {1937-1939}, doi = {10.1158/0008-5472.CAN-21-0300}, pmid = {34003771}, issn = {1538-7445}, mesh = {*Breast Neoplasms/drug therapy ; Female ; Humans ; *Pharmaceutical Preparations ; Receptor, ErbB-2 ; Trastuzumab/therapeutic use ; }, abstract = {The identification of microbial networks that are predictive of disease progression and response to therapy will not only increase our understanding of the connection between microbiota and breast cancer, but also pave the way for the development of novel microbiota-based therapeutic interventions. The study by Di Modica and colleagues points to the existence of specific microbiota in patients with HER2[+] breast cancer that can influence their response to trastuzumab. This information can potentially be used to develop novel therapeutic regimens combining fecal microbiota transplant with standard cancer therapy.See related article by Di Modica et al., p. 2195.}, }
@article {pmid34003768, year = {2021}, author = {Baruch, EN and Wang, J and Wargo, JA}, title = {Gut Microbiota and Antitumor Immunity: Potential Mechanisms for Clinical Effect.}, journal = {Cancer immunology research}, volume = {9}, number = {4}, pages = {365-370}, doi = {10.1158/2326-6066.CIR-20-0877}, pmid = {34003768}, issn = {2326-6074}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; }, mesh = {CD8-Positive T-Lymphocytes/*immunology ; Diet Therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunotherapy ; Neoplasms/immunology/*microbiology/therapy ; Probiotics ; Th1 Cells/*immunology ; }, abstract = {Several landmark preclinical studies have shown an association between the gut microbiota and the effectiveness of immunotherapy for cancer. These studies have sparked clinical trials aimed at modulating the gut microbiota in order to improve clinical response rates to immunotherapy. Despite this, the mechanisms through which the gut microbiota influences the effectiveness of immunotherapy are still incompletely characterized. Preclinical and preliminary clinical findings from numerous types of gut microbiota modulation studies, including fecal transplantation, probiotics, consortia, and diet, demonstrate that favorable microbiota modulation is associated with increased intratumoral infiltration of CD8[+] effector T cells. This CD8[+] T-cell infiltration is often associated with enhanced intratumoral activity of T-helper type 1 cells and dendritic cells and a lower density of immunosuppressive cells. Herein, we discuss how gut microbiota may affect the activity of immune cells by at least three interlacing mechanisms: activation of pattern recognition receptors, molecular mimicry, and impact of metabolites. We also discuss the therapeutic potential and limitations of the different gut microbiota modulation techniques and their putative mechanisms of immune activation.}, }
@article {pmid34000958, year = {2021}, author = {Madsen, AMA and Halkjær, SI and Christensen, AH and Günther, S and Browne, PD and Kallemose, T and Hansen, LH and Petersen, AM}, title = {The effect of faecal microbiota transplantation on abdominal pain, stool frequency, and stool form in patients with moderate-to-severe irritable bowel syndrome: results from a randomised, double-blind, placebo-controlled study.}, journal = {Scandinavian journal of gastroenterology}, volume = {56}, number = {7}, pages = {761-769}, doi = {10.1080/00365521.2021.1915375}, pmid = {34000958}, issn = {1502-7708}, mesh = {Abdominal Pain/etiology/therapy ; Adult ; Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome/therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis. Therefore, faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. In this study, we analysed previously unexamined data from our randomised, double-blind, placebo-controlled study (trial registration number NCT02788071). The objective was to evaluate the effect of FMT on abdominal pain, stool frequency, and stool form.<br><br>METHOD: The study included 52 adult patients with moderate-to-severe IBS assigned randomly to treatment with FMT capsules or placebo capsules (1:1) for 12&#x2009;days. The patients were followed for a total of six months, during which they kept a daily symptom diary tracking their abdominal pain on a scale from 0-10 and their bowel movements using the Bristol Stool Form Scale (BSFS). Diary data were not collected before treatment start.<br><br>RESULTS: A statistically significant improvement in stool frequency was found in the FMT group from during treatment to post-treatment and 1&#x2009;month. No statistically significant differences were found between groups at any time during the study for any of abdominal pain, stool frequency, and stool form (as measured by weighted stool score).<br><br>CONCLUSION: In this analysis of results from a randomised, double-blind, placebo-controlled study, we found no clinically beneficial effect of FMT on abdominal pain, stool frequency, or stool form. However, since the current literature on the potential role of FMT in treating IBS shows conflicting results, further studies are required. To assess treatment efficacy, we recommend future studies to include daily symptom diaries both before and after treatment intervention.}, }
@article {pmid33999048, year = {2021}, author = {Li, QM and Zha, XQ and Zhang, WN and Liu, J and Pan, LH and Luo, JP}, title = {Laminaria japonica polysaccharide prevents high-fat-diet-induced insulin resistance in mice via regulating gut microbiota.}, journal = {Food &amp; function}, volume = {12}, number = {12}, pages = {5260-5273}, doi = {10.1039/d0fo02100h}, pmid = {33999048}, issn = {2042-650X}, mesh = {Animals ; Atherosclerosis/prevention &amp; control ; Diet, High-Fat/*adverse effects ; Dietary Carbohydrates/pharmacology ; Dysbiosis ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Homeostasis ; Inflammation ; *Insulin Resistance ; Laminaria/*metabolism ; Male ; Metabolic Diseases/pathology/prevention &amp; control ; Mice ; Mice, Inbred C57BL ; Obesity/prevention &amp; control ; Polysaccharides/*pharmacology ; }, abstract = {Insulin resistance has become a worldwide nutrition and metabolic health problem due to the lack of effective protective agents. Laminaria japonica is a well-known marine vegetable. Purified Laminaria japonica polysaccharide (LJP61A) can inhibit atherosclerosis in high-fat-diet (HFD)-fed mice via ameliorating insulin resistance. In this study, we aimed to clarify the mechanism by which LJP61A ameliorates HFD-induced insulin resistance. The results indicated that HFD-induced insulin resistance, obesity, systematic inflammation, metabolic endotoxemia, and gut permeability in mice could be reduced by LJP61A. Gut microbiota analysis showed that the gut microbiota dysbiosis of HFD-fed mice, especially the reduction in mucin-degrading Akkermansia, could be reversed by LJP61A. Additionally, the reduction in mucin-producing goblet cells in HFD-fed mice could also be reversed by LJP61A. Moreover, insulin resistance, obesity, systematic inflammation, metabolic endotoxemia, and gut microbiota dysbiosis in HFD-fed mice could also be alleviated by faecal transplant from LJP61A-treated mice. Overall, LJP61A might be used as a prebiotic to ameliorate HFD-induced insulin resistance and associated metabolic disorders via regulating gut microbiota, especially Akkermansia.}, }
@article {pmid33996366, year = {2021}, author = {Niina, A and Kibe, R and Suzuki, R and Yuchi, Y and Teshima, T and Matsumoto, H and Kataoka, Y and Koyama, H}, title = {Fecal microbiota transplantation as a new treatment for canine inflammatory bowel disease.}, journal = {Bioscience of microbiota, food and health}, volume = {40}, number = {2}, pages = {98-104}, pmid = {33996366}, issn = {2186-6953}, abstract = {In human medicine, fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection. It has also been tested as a treatment for multiple gastrointestinal diseases, including inflammatory bowel disease (IBD). However, only a few studies have focused on the changes in the microbiome following FMT for canine IBD. Here, we performed FMT in nine dogs with IBD using the fecal matter of healthy dogs and investigated the subsequent changes in the fecal microbiome and clinical signs. In three dogs, the fecal microbiome was examined by 16S rRNA sequencing. Fusobacteria were observed at a low proportion in dogs with IBD. However, the post-FMT microbiome became diverse and showed a significant increase in Fusobacteria proportion. Fusobacterium was detected in the nine dogs by quantitative polymerase chain reaction. The proportion of Fusobacterium in the post-FMT fecal microbiome was significantly increased (p<0.05). The changes in clinical signs (e.g., vomiting, diarrhea, and weight loss) were evaluated according to the canine inflammatory bowel disease activity index. The score of this index significantly decreased in all dogs (p<0.05) with improvements in clinical signs. These improvements were related to the changes in the proportion of microbes, particularly the increase in Fusobacterium. The dogs with IBD showed a lower proportion of Fusobacterium than healthy dogs. This suggests that a low proportion of Fusobacterium is a characteristic feature of canine IBD and that Fusobacterium is involved in this disease. The results of this study may help elucidate the pathogenesis of this disease and its association with Fusobacterium.}, }
@article {pmid33995583, year = {2021}, author = {Chaar, A and Feuerstadt, P}, title = {Evolution of clinical guidelines for antimicrobial management of Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211011953}, pmid = {33995583}, issn = {1756-283X}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, abstract = {Clostridioides difficile infection (CDI) has been an epidemic for many years. Our biggest challenge in treating CDI is preventing recurrence, which is seen in approximately 25% of patients with initial infection and in 40-60% of those with subsequent episodes. Given the major disease burden of this infection, appropriate data-driven treatment remains essential. Clinical treatment guidelines provide an unbiased critical analysis of the literature, integrating the quality of the available data to make recommendations. As CDI has been evolving and more research has become available, the frequency of guideline issue from various global societies has increased, as has the detail of the recommendations to fit more relevant clinical scenarios. In this review, we will discuss clinical guideline recommendations over three time periods: The Initial Guidelines 1995-1997, The Second Wave 2009-2013, and The Modern Era 2014-present. We see the changing recommendations from metronidazole or vancomycin for initial infection during earlier times to preferential treatment with fidaxomicin within the Infectious Diseases Society of America (IDSA) and Society of Healthcare Epidemiology of America (SHEA) joint guidelines provisional update in late 2020. The recommended treatments for first recurrence were initially with the same antimicrobial as the first episode but have since changed to having multiple options for one or more recurrences. We have also seen the addition of immune boosting treatments, including fecal microbiota transplantation (FMT)/microbiota restoration therapy (MRT) and bezlotoxumab in the more modern recommendations. As the guidelines are evolving with the times, it remains important to understand the differences among them so we can apply this information clinically and optimize patient outcomes.}, }
@article {pmid33994854, year = {2021}, author = {Yu, M and Alimujiang, M and Hu, L and Liu, F and Bao, Y and Yin, J}, title = {Berberine alleviates lipid metabolism disorders via inhibition of mitochondrial complex I in gut and liver.}, journal = {International journal of biological sciences}, volume = {17}, number = {7}, pages = {1693-1707}, pmid = {33994854}, issn = {1449-2288}, mesh = {Animals ; Berberine/*pharmacology ; Disease Models, Animal ; Electron Transport Complex I/*deficiency/drug effects/metabolism ; Intestines/drug effects/*metabolism/ultrastructure ; Lipid Metabolism/*drug effects ; Lipid Metabolism Disorders/*drug therapy/metabolism/pathology ; Liver/drug effects/*metabolism/ultrastructure ; Male ; Mice ; Mice, Inbred AKR ; Microscopy, Electron, Transmission ; Mitochondrial Diseases/metabolism/pathology ; Oxidation-Reduction ; }, abstract = {This study is to investigate the relationship between berberine (BBR) and mitochondrial complex I in lipid metabolism. BBR reversed high-fat diet-induced obesity, hepatic steatosis, hyperlipidemia and insulin resistance in mice. Fatty acid consumption, β-oxidation and lipogenesis were attenuated in liver after BBR treatment which may be through reduction in SCD1, FABP1, CD36 and CPT1A. BBR promoted fecal lipid excretion, which may result from the reduction in intestinal CD36 and SCD1. Moreover, BBR inhibited mitochondrial complex I-dependent oxygen consumption and ATP synthesis of liver and gut, but no impact on activities of complex II, III and IV. BBR ameliorated mitochondrial swelling, facilitated mitochondrial fusion, and reduced mtDNA and citrate synthase activity. BBR decreased the abundance and diversity of gut microbiome. However, no change in metabolism of recipient mice was observed after fecal microbiota transplantation from BBR treated mice. In primary hepatocytes, BBR and AMPK activator A769662 normalized oleic acid-induced lipid deposition. Although both the agents activated AMPK, BBR decreased oxygen consumption whereas A769662 increased it. Collectively, these findings indicated that BBR repressed complex I in gut and liver and consequently inhibited lipid metabolism which led to alleviation of obesity and fatty liver. This process was independent of intestinal bacteria.}, }
@article {pmid33989733, year = {2021}, author = {Spyrou, N and Vallianou, N and Kadillari, J and Dalamaga, M}, title = {The interplay of obesity, gut microbiome and diet in the immune check point inhibitors therapy era.}, journal = {Seminars in cancer biology}, volume = {73}, number = {}, pages = {356-376}, doi = {10.1016/j.semcancer.2021.05.008}, pmid = {33989733}, issn = {1096-3650}, mesh = {Animals ; *Diet ; *Gastrointestinal Microbiome ; Humans ; *Immune Checkpoint Inhibitors/therapeutic use ; Neoplasms/*drug therapy ; *Obesity ; Risk Factors ; }, abstract = {Immunotherapy has recently emerged as a promising treatment option for many patients, revolutionizing the established therapeutic approach against cancer. Immune checkpoints inhibitors (ICIs) have demonstrated clinical activity in a wide spectrum of malignancies; however, only a minority of patients exhibit durable responses. This response heterogeneity may be partly attributed to host related factors, such as body mass index (BMI), diet and gut microbiome, that have recently emerged as strong influences in ICI responsiveness. Obesity not only directly impacts on cancer promotion but also on the immune homeostasis and the elimination, equilibrium, and escape phases of immune-editing. Paradoxically, emerging clinical data indicate that obese patients are benefited from ICI therapy when compared to normal BMI cancer patients. Interestingly, strong evidence supports the role of the microbiome in cancer immunotherapy, with several recent animal, translational/hybrid and clinical studies demonstrating its influence in the response to ICIs across several malignancies. Noteworthy, nutrition, through its well-established links to obesity, microbiome composition and oncogenicity, may contribute towards leveraging its effects in favor of cancer patients alongside with gold standard treatments. The aim of this review is to delineate the associations of ICIs with obesity, host microbiome and nutrition, and to explore how these factors can be effectively leveraged in enhancing the effectiveness of immunotherapy. More specific aims include the determination of how patients with obesity are differentially affected by ICI therapy; how the host microbiome affects response to ICIs; and how the microbiome itself is modulated by obesity and nutrition. In conclusion, immunometabolism, microbiome and nutrition research present the potential to offer unique tools in unleashing ICIs full potential; providing host-derived, actionable, modifiable targets directly associated with therapeutic outcomes that can be efficiently leveraged. Future efforts, provided that they adhere to robustness of methodology, can facilitate transferring these findings, from bench to bedside.}, }
@article {pmid33989072, year = {2021}, author = {Bonde, A and Daly, S and Kirsten, J and Kondapaneni, S and Mellnick, V and Menias, CO and Katabathina, VS}, title = {Human Gut Microbiota-associated Gastrointestinal Malignancies: A Comprehensive Review.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {41}, number = {4}, pages = {1103-1122}, doi = {10.1148/rg.2021200168}, pmid = {33989072}, issn = {1527-1323}, mesh = {Ecosystem ; *Epstein-Barr Virus Infections ; *Gastrointestinal Microbiome ; *Gastrointestinal Neoplasms ; Herpesvirus 4, Human ; Humans ; }, abstract = {The human gastrointestinal tract houses trillions of microbes. The gut and various types of microorganisms, including bacteria, viruses, fungi, and archaea, form a complex ecosystem known as the gut microbiota, and the whole genome of the gut microbiota is referred to as the gut microbiome. The gut microbiota is essential for homeostasis and the overall well-being of a person and is increasingly considered an adjunct "virtual organ," with a complexity level comparable to that of the other organ systems. The gut microbiota plays an essential role in nutrition, local mucosal homeostasis, inflammation, and the mucosal immune system. An imbalanced state of the gut microbiota, known as dysbiosis, can predispose to development of various gastrointestinal malignancies through three speculated pathogenic mechanisms: (a) direct cytotoxic effects with damage to the host DNA, (b) disproportionate proinflammatory signaling inducing inflammation, and (c) activation of tumorigenic pathways or suppression of tumor-suppressing pathways. Several microorganisms, including Helicobacter pylori, Epstein-Barr virus, human papillomavirus, Mycoplasma species, Escherichia coli, and Streptococcus bovis, are associated with gastrointestinal malignancies such as esophageal adenocarcinoma, gastric adenocarcinoma, gastric mucosa-associated lymphoid tissue lymphoma, colorectal adenocarcinoma, and anal squamous cell carcinoma. Imaging plays a pivotal role in diagnosis and management of microbiota-associated gastrointestinal malignancies. Appropriate use of probiotics, fecal microbiota transplantation, and overall promotion of the healthy gut are ongoing areas of research for prevention and treatment of malignancies. Online supplemental material is available for this article. [©]RSNA, 2021.}, }
@article {pmid33988462, year = {2021}, author = {Cheslow, L and Snook, AE and Waldman, SA}, title = {Emerging targets for the diagnosis of Parkinson's disease: examination of systemic biomarkers.}, journal = {Biomarkers in medicine}, volume = {15}, number = {8}, pages = {597-608}, pmid = {33988462}, issn = {1752-0371}, support = {P30 CA056036/CA/NCI NIH HHS/United States ; R01 CA204481/CA/NCI NIH HHS/United States ; R01 CA206026/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biomarkers/*metabolism ; Disease Progression ; Humans ; Parkinson Disease/*diagnosis/*metabolism ; }, abstract = {Parkinson's disease (PD) is a highly prevalent and irreversible neurodegenerative disorder that is typically diagnosed in an advanced stage. Currently, there are no approved biomarkers that reliably identify PD patients before they have undergone extensive neuronal damage, eliminating the opportunity for future disease-modifying therapies to intervene in disease progression. This unmet need for diagnostic and therapeutic biomarkers has fueled PD research for decades, but these efforts have not yet yielded actionable results. Recently, studies exploring mechanisms underlying PD progression have offered insights into multisystemic contributions to pathology, challenging the classic perspective of PD as a disease isolated to the brain. This shift in understanding has opened the door to potential new biomarkers from multiple sites in the body. This review focuses on emerging candidates for PD biomarkers in the context of current diagnostic approaches and multiple organ systems that contribute to disease.}, }
@article {pmid33985595, year = {2021}, author = {Wilson, BC and Vatanen, T and Jayasinghe, TN and Leong, KSW and Derraik, JGB and Albert, BB and Chiavaroli, V and Svirskis, DM and Beck, KL and Conlon, CA and Jiang, Y and Schierding, W and Holland, DJ and Cutfield, WS and O'Sullivan, JM}, title = {Strain engraftment competition and functional augmentation in a multi-donor fecal microbiota transplantation trial for obesity.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {107}, pmid = {33985595}, issn = {2049-2618}, mesh = {Adolescent ; Australia ; *Dysbiosis/therapy ; *Fecal Microbiota Transplantation ; Feces ; Female ; Humans ; Male ; Obesity/therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: Donor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment have not yet been assessed in the context of multiple donors.<br><br>METHODS: We conducted a double-blinded randomized control trial of FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6, 12, and 26 weeks post-treatment were analyzed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients' gut microbiomes.<br><br>RESULTS: Multi-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterized by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardize FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains.<br><br>CONCLUSION: Our study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harbored diverse microbial species and genes and were characterized by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity.<br><br>TRIAL REGISTRATION: The Gut Bugs trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001351505).<br><br>TRIAL PROTOCOL: The trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.}, }
@article {pmid33985520, year = {2021}, author = {Kuai, XY and Yao, XH and Xu, LJ and Zhou, YQ and Zhang, LP and Liu, Y and Pei, SF and Zhou, CL}, title = {Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {98}, pmid = {33985520}, issn = {1475-2859}, support = {LCZX201814//Suzhou Health and Family Planning Commission/ ; SYSD2020142//Suzhou Municipal Science and Technology Bureau/ ; }, mesh = {Aged ; Bacteria/classification/genetics/*growth &amp; development/isolation &amp; purification ; Constipation/*prevention &amp; control ; Dysbiosis/microbiology/prevention &amp; control ; Fecal Microbiota Transplantation/*methods/*standards ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; Male ; Middle Aged ; Parkinson Disease/*complications ; Prospective Studies ; Quality of Life ; }, abstract = {Parkinson's disease (PD) is a neurodegenerative disorder and 70-80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.}, }
@article {pmid33983361, year = {2021}, author = {Lu, C and Chen, J and Yi, C and Han, J and Shi, Q and Li, J and Liu, B and Zhou, J and Su, X}, title = {Gut microbiota mediated the protective effects of tuna oil on collagen-induced arthritis in mice.}, journal = {Food &amp; function}, volume = {12}, number = {12}, pages = {5387-5398}, doi = {10.1039/d1fo00709b}, pmid = {33983361}, issn = {2042-650X}, mesh = {Animals ; Ankle Joint/diagnostic imaging/pathology ; Arthritis, Experimental/*metabolism ; Arthritis, Rheumatoid/chemically induced/pathology/*therapy ; Biomarkers ; Collagen/*adverse effects ; Cytokines/analysis ; Fecal Microbiota Transplantation ; Fish Oils/*pharmacology ; Gastrointestinal Microbiome/*physiology ; Inflammation/pathology ; Male ; Mice ; Mice, Inbred ICR ; Phosphorylation ; Signal Transduction/drug effects ; Tuna/*metabolism ; Wnt1 Protein ; beta Catenin ; }, abstract = {Rheumatoid arthritis is emerging as a chronic autoimmune disease worldwide. In this study, the beneficial effects of tuna oil (TO) on collagen-induced arthritis (CIA) mice were investigated. Dietary administration of TO relieved arthritis severity and joint bone erosion, and ameliorated systemic inflammation. Furthermore, TO treatments regulated the phosphorylation of nuclear factor-kappa B (NF-κB) and Wnt1/β-catenin signaling pathways in the joint, enhanced osteoblastogenesis biomarkers and suppressed osteoclastogenesis biomarkers, and subsequently re-balanced bone remodeling. Moreover, the impaired intestinal epithelial barrier was repaired after TO treatments, along with gut microbiota modulation. By employing fecal microbiota transplantation, we clarified that the beneficial effects of TO in CIA alleviation were mediated by the modulated gut microbiota. These results indicated that gut microbiota mediated the protective effects of tuna oil on collagen-induced arthritis in mice.}, }
@article {pmid33982930, year = {2021}, author = {Gupta, S and Mullish, BH and Allegretti, JR}, title = {Fecal Microbiota Transplantation: The Evolving Risk Landscape.}, journal = {The American journal of gastroenterology}, volume = {116}, number = {4}, pages = {647-656}, doi = {10.14309/ajg.0000000000001075}, pmid = {33982930}, issn = {1572-0241}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Humans ; Recurrence ; }, abstract = {Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT.}, }
@article {pmid33982127, year = {2021}, author = {Wang, B and Wang, L and Wang, H and Dai, H and Lu, X and Lee, YK and Gu, Z and Zhao, J and Zhang, H and Chen, W and Wang, G}, title = {Targeting the Gut Microbiota for Remediating Obesity and Related Metabolic Disorders.}, journal = {The Journal of nutrition}, volume = {151}, number = {7}, pages = {1703-1716}, doi = {10.1093/jn/nxab103}, pmid = {33982127}, issn = {1541-6100}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Metabolic Diseases ; Obesity ; Prebiotics ; *Probiotics ; }, abstract = {The rate of obesity is rapidly increasing and has become a health and economic burden worldwide. As recent studies have revealed that the gut microbiota is closely linked to obesity, researchers have used various approaches to modulate the gut microbiota to treat the condition. Dietary composition and energy intake strongly affect the composition and function of the gut microbiota. Intestinal microbial changes alter the composition of bile acids and fatty acids and regulate bacterial lipopolysaccharide production, all of which influence energy metabolism and immunity. Evidence also suggests that remodeling the gut microbiota through intake of probiotics, prebiotics, fermented foods, and dietary plants, as well as by fecal microbiota transplantation, are feasible methods to remediate obesity.}, }
@article {pmid33981340, year = {2021}, author = {Liu, X and Li, Y and Wu, K and Shi, Y and Chen, M}, title = {Fecal Microbiota Transplantation as Therapy for Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.}, journal = {Gastroenterology research and practice}, volume = {2021}, number = {}, pages = {6612970}, pmid = {33981340}, issn = {1687-6121}, abstract = {AIM: Increasing evidence supports the role of the gut microbiota in the etiology of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection; however, its efficacy in UC is still controversial. A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of FMT for treatment of active UC.<br><br>METHODS: We searched Cochrane, Medline, Web of Science, and Embase from inception to February 2020. Randomized controlled trials (RCTs) recruiting adults with active UC, which compared FMT with controls, were eligible. The primary outcome was combined clinical remission with endoscopic remission/response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Relative risk (RR) with 95% confidence interval (CI) is reported.<br><br>RESULTS: Five RCTs with 292 participants were eligible for inclusion. When data were pooled for all patients, FMT was associated with a higher combined clinical remission with endoscopic remission/response; the RR of combined outcome not achieving after FMT vs. control was 0.79 (95% CI 0.70-0.88). FMT delivered via lower gastrointestinal route was superior to upper gastrointestinal route with regard to combined clinical remission with endoscopic remission/response (RR = 0.79, 95% CI 0.70-0.89). FMT with pooled donor stool (RR = 0.69, 95% CI 0.56-0.85) and higher frequency of administration (RR = 0.76, 95% CI 0.62-0.93) may be more effective with regard to clinical remission. There was no statistically significant difference in serious adverse events with FMT compared with controls (RR = 0.98, 95% CI 0.93-1.03).<br><br>CONCLUSION: FMT shows a promising perspective with comparable safety and favorable clinical efficacy for the treatment of active UC in the short term. However, further larger, more rigorously conducted RCTs of FMT in UC are still needed in order to resolve the controversial questions.}, }
@article {pmid33978386, year = {2021}, author = {Yang, X and Huang, Z and He, J and Chen, Y}, title = {The Elevated Risk of Recurrent Clostridioides Difficile Infection in Patients with Inflammatory Bowel Disease: a Systematic Review and Meta-analysis.}, journal = {Clinical laboratory}, volume = {67}, number = {5}, pages = {}, doi = {10.7754/Clin.Lab.2020.200428}, pmid = {33978386}, issn = {1433-6510}, mesh = {Clostridioides ; *Clostridium Infections/diagnosis/epidemiology ; *Colitis, Ulcerative/complications/diagnosis ; Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases/complications/diagnosis ; }, abstract = {BACKGROUND: The association between inflammatory bowel disease (IBD) and the risk of recurrent Clostridioides difficile infection (rCDI) is still controversial. This systematic review and meta-analysis aims to clarify whether the risk of rCDI is associated with IBD based on published data.<br><br>METHODS: A systematic review and meta-analysis was conducted in English and Chinese databases, covering all available publications until date 01/01/2020. The statistical analysis was performed by RevMan 5.3 and odds ratios (ORs) combined with 95% confidence intervals (CI) were calculated to explore the IBD-rCDI association.<br><br>RESULTS: A total of 4,417 IBD cases and 355,769 control cases in 14 independent studies from 2007 to 2019 were included. Compared with non-IBD, IBD was associated with an increased risk of rCDI (OR = 1.63, CI = 1.09 - 2.43, p = 0.02). In addition, the risk of rCDI was particularly and significantly increased in IBD patients at the young age (&#x2264; 50, OR = 1.58, CI = 1.02 - 2.44, p = 0.04), but not in patients at the old age (> 50, OR = 2.08, CI = 0.65 - 6.61, p = 0.21). Compared with Crohn's disease (CD), no significant differences existed in the risk of rCDI in ulcerative colitis (UC) (OR = 1.22, CI = 0.81 - 1.85, p = 0.34). Additionally, the risk of rCDI was not significantly different between UC and CD, in patients receiving FMT (OR = 1.41, CI = 0.65 - 3.06, p = 0.38) or no FMT treatment (OR = 1.16, CI = 0.71 - 1.88, p = 0.56).<br><br>CONCLUSIONS: The risk of rCDI was significantly increased in IBD patients, in particular in those age below 50. Compared with CD, no significant differences of the risk of rCDI was observed in UC.}, }
@article {pmid33966043, year = {2021}, author = {Derosa, L and Zitvogel, L}, title = {Fecal microbiota transplantation: can it circumvent resistance to PD-1 blockade in melanoma?.}, journal = {Signal transduction and targeted therapy}, volume = {6}, number = {1}, pages = {178}, pmid = {33966043}, issn = {2059-3635}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Melanoma/drug therapy ; Programmed Cell Death 1 Receptor ; }, }
@article {pmid33962692, year = {2021}, author = {Mayneris-Perxachs, J and Cardellini, M and Hoyles, L and Latorre, J and Davato, F and Moreno-Navarrete, JM and Arnoriaga-Rodríguez, M and Serino, M and Abbott, J and Barton, RH and Puig, J and Fernández-Real, X and Ricart, W and Tomlinson, C and Woodbridge, M and Gentileschi, P and Butcher, SA and Holmes, E and Nicholson, JK and Pérez-Brocal, V and Moya, A and Clain, DM and Burcelin, R and Dumas, ME and Federici, M and Fernández-Real, JM}, title = {Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {104}, pmid = {33962692}, issn = {2049-2618}, support = {MR/L01632X/1/MRC_/Medical Research Council/United Kingdom ; MR/M501797/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Gastrointestinal Microbiome/genetics ; Iron ; Mice ; *Non-alcoholic Fatty Liver Disease ; Obesity ; }, abstract = {BACKGROUND: The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear.<br><br>RESULTS: Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery n = 49 and validation n = 628) and an independent cohort formed by both individuals with and without obesity (n = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality. Specifically, ferritin had strong negative associations with the Pasteurellaceae, Leuconostocaceae and Micrococcaea families. It also had consistent negative associations with several Veillonella, Bifidobacterium and Lactobacillus species, but positive associations with Bacteroides and Prevotella spp. Notably, the ferritin-associated bacterial families had a strong correlation with iron-related liver genes. In addition, several bacterial functions related to iron metabolism (transport, chelation, heme and siderophore biosynthesis) and NAFLD (fatty acid and glutathione biosynthesis) were also associated with the host serum ferritin levels. This iron-related microbiome signature was linked to a transcriptomic and metabolomic signature associated to the degree of liver fat accumulation through hepatic glucose metabolism. In particular, we found a consistent association among serum ferritin, Pasteurellaceae and Micrococcacea families, bacterial functions involved in histidine transport, the host circulating histidine levels and the liver expression of GYS2 and SEC24B. Serum ferritin was also related to bacterial glycine transporters, the host glycine serum levels and the liver expression of glycine transporters. The transcriptomic findings were replicated in human primary hepatocytes, where iron supplementation also led to triglycerides accumulation and induced the expression of lipid and iron metabolism genes in synergy with palmitic acid. We further explored the direct impact of the microbiome on iron metabolism and liver fact accumulation through transplantation of faecal microbiota into recipient's mice. In line with the results in humans, transplantation from 'high ferritin donors' resulted in alterations in several genes related to iron metabolism and fatty acid accumulation in recipient's mice.<br><br>CONCLUSIONS: Altogether, a significant interplay among the gut microbiome, iron status and liver fat accumulation is revealed, with potential significance for target therapies. Video abstract.}, }
@article {pmid33961887, year = {2021}, author = {Pai, N and Popov, J and Hill, L and Hartung, E and Grzywacz, K and Moayyedi, P and , }, title = {Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects.}, journal = {Gastroenterology}, volume = {161}, number = {2}, pages = {388-393.e3}, doi = {10.1053/j.gastro.2021.04.067}, pmid = {33961887}, issn = {1528-0012}, support = {RN279389 &#x2013; 358033//CIHR/Canada ; }, mesh = {Adolescent ; Age Factors ; Canada ; Child ; Child, Preschool ; Colitis, Ulcerative/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Male ; Patient Selection ; Pilot Projects ; Sample Size ; Time Factors ; Treatment Outcome ; }, }
@article {pmid33961870, year = {2021}, author = {Kano, T and Suzuki, H and Makita, Y and Fukao, Y and Suzuki, Y}, title = {Nasal-associated lymphoid tissue is the major induction site for nephritogenic IgA in murine IgA nephropathy.}, journal = {Kidney international}, volume = {100}, number = {2}, pages = {364-376}, doi = {10.1016/j.kint.2021.04.026}, pmid = {33961870}, issn = {1523-1755}, mesh = {Animals ; Glomerular Mesangium ; *Glomerulonephritis, IGA ; Immunoglobulin A ; Lymphoid Tissue ; Mice ; Mice, Inbred Strains ; }, abstract = {Dysregulation of mucosal immunity may play a role in the pathogenesis of IgA nephropathy (IgAN). However, it is unclear whether the nasal-associated lymphoid tissue (NALT) or gut-associated lymphatic tissue is the major induction site of nephritogenic IgA synthesis. To examine whether exogenous mucosal antigens exacerbate the pathogenesis of IgAN, we assessed the disease phenotypes of IgAN-onset ddY mice housed germ-free. These mice were transferred to a specific pathogen-free environment and divided into three groups: challenged with the Toll-like receptor 9 (TLR9) ligand CpG-oligodeoxynucleotide, fecal transplantation, and the untreated control group. The levels of aberrantly glycosylated IgA and IgG-IgA immune complexes were measured in the serum and supernatant of cultured cells purified from the NALT, mesenteric lymph nodes, and Peyer's patch. Although the germ-free IgAN-onset ddY mice did not develop IgAN, they showed aggravation of kidney injury with mesangial IgA deposition after transfer to the specific pathogen-free state. The NALT cells produced more aberrantly glycosylated IgA than those from the mesenteric lymph node and Peyer's patch, resulting in induction of IgG-IgA immune complexes formation. Additionally, TLR9 enhanced the production of nephritogenic IgA and IgG-IgA immune complexes by nasal-associated lymphoid but not gut-associated lymphatic cells. Furthermore, the germ-free IgAN-onset ddY mice nasally immunized with CpG-oligonucleotide showed aggravation of kidney injury with mesangial IgA deposition, whereas those that received fecal transplants did not develop IgAN. Thus, NALT is the major induction site of the production of aberrantly glycosylated IgA in murine IgAN.}, }
@article {pmid33961738, year = {2021}, author = {Verbeke, F and De Spiegeleer, B}, title = {Faecal microbiota transplants: Why do we not consider them as Advanced Therapy Medicinal Products?.}, journal = {United European gastroenterology journal}, volume = {9}, number = {4}, pages = {519-520}, pmid = {33961738}, issn = {2050-6414}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid33961710, year = {2021}, author = {Singh, AR and Sachan, A and Shankar, S}, title = {Letter: faecal microbiota transplant in Clostridioides difficile infection: learning from the common water hyacinth.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {53}, number = {11}, pages = {1244-1245}, doi = {10.1111/apt.16370}, pmid = {33961710}, issn = {1365-2036}, mesh = {Clostridioides ; *Clostridium Infections/therapy ; *Eichhornia ; Fecal Microbiota Transplantation ; Humans ; Vancomycin ; Water ; }, }
@article {pmid33959193, year = {2021}, author = {Yadav, D and Khanna, S}, title = {Safety of fecal microbiota transplantation for Clostridioides difficile infection focusing on pathobionts and SARS-CoV-2.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211009694}, pmid = {33959193}, issn = {1756-283X}, abstract = {Clostridioides difficile infection (CDI) is a consequence of flagrant use of antibiotics, an aging population with increasing comorbidities, and increased hospitalizations. The treatment of choice for CDI is antibiotics (vancomycin or fidaxomicin), with a possibility of recurrent CDI despite lack of additional risk factors for CDI. For the last 10 years, fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, with success rates of over 85% compared with less than 50% with antibiotics for multiple recurrent CDI. Along with the success of FMT, several adverse and serious adverse events with FMT have been reported. These range from self-limiting abdominal pain to death due to severe sepsis. This review focuses on the safety of FMT, emphasizing the reports of transmission of pathobionts like extended-spectrum beta lactamase Escherichia coli and Shiga toxin-producing E. coli. The severe acute respiratory syndrome coronavirus-2 is a potential pathogen that could be transmitted via FMT during the COVID-19 pandemic. The challenges faced by clinicians for donor screening, clinical trials, and other aspects of FMT during the pandemic are discussed.}, }
@article {pmid33958592, year = {2021}, author = {Chen, PJ and Nakano, T and Lai, CY and Chang, KC and Chen, CL and Goto, S}, title = {Daily full spectrum light exposure prevents food allergy-like allergic diarrhea by modulating vitamin D3 and microbiota composition.}, journal = {NPJ biofilms and microbiomes}, volume = {7}, number = {1}, pages = {41}, pmid = {33958592}, issn = {2055-5008}, mesh = {Activities of Daily Living ; Animals ; Antibody Formation/immunology ; Biomarkers ; Cholecalciferol/*metabolism ; Cytokines/metabolism ; Diarrhea/*etiology/*prevention &amp; control ; Disease Management ; Disease Models, Animal ; Disease Susceptibility ; Dysbiosis ; Environmental Exposure ; Fecal Microbiota Transplantation/methods ; Female ; Food Hypersensitivity/*etiology/*prevention &amp; control ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/immunology/metabolism/pathology ; Mice ; Oxidative Stress ; Phototherapy ; *Sunlight ; T-Lymphocytes/immunology/metabolism ; }, abstract = {The importance of sun exposure on human health is well recognized, and a recent trend in the avoidance of sun exposure has led to the risk of missing the beneficial effects such as vitamin D3 biogenesis. Vitamin D3 insufficiency is one of the risk factors for the development of food allergies (FAs), and vitamin D3 status controls gut homeostasis by modulating the microbiota. This study aimed to explore the impact of daily full spectrum light exposure (phototherapy) on the pathogenesis of FAs. Phototherapy ameliorated allergic diarrhea and improved FA-associated vitamin D3 insufficiency and dysbiosis. Fecal microbiota transplantation (FMT) of FA donor feces induced allergic diarrhea with OVA-specific IgE elevation in naïve mice. In contrast, FMT of naïve donor feces ameliorated allergic diarrhea in established FA mice, suggesting the involvement of the microbiota composition in FA. Phototherapy is an alternative approach for the prevention of FA-like allergic diarrhea through the modulation of vitamin D3 status and microbiota composition.}, }
@article {pmid33957990, year = {2021}, author = {Han, Q and Wang, J and Li, W and Chen, ZJ and Du, Y}, title = {Androgen-induced gut dysbiosis disrupts glucolipid metabolism and endocrinal functions in polycystic ovary syndrome.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {101}, pmid = {33957990}, issn = {2049-2618}, mesh = {Androgens ; Animals ; Dysbiosis/chemically induced ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; *Polycystic Ovary Syndrome/chemically induced ; Rats ; }, abstract = {BACKGROUND: The characteristics of polycystic ovary syndrome (PCOS), a common reproductive endocrinal disorder, are high incidence, complicated aetiology and poor therapeutic effects. PCOS patients frequently exhibit gut dysbiosis; however, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear.<br><br>RESULTS: In this study, gut dysbiosis was reproduced in dehydroepiandrosterone (DHEA)-induced PCOS-like rats. An antibiotic cocktail was used to eliminate gut microbiota during DHEA treatment; however, depletion of the gut microbiota did not prevent the occurrence of PCOS phenotypes in DHEA-treated rats. DHEA-shaped gut microbiota transplanted to pseudo germ-free recipients trigged disturbances in hepatic glucolipid metabolism and reproductive hormone imbalance. The clinical features of PCOS may be correlated with the relative abundance of gut microbes and the levels of faecal metabolites in faecal microbiota transplantation&#xa0;(FMT) recipient rats.<br><br>CONCLUSION: These findings indicate that androgen-induced gut microbiota dysbiosis may aggravate metabolic and endocrinal malfunction in PCOS. Video Abstract.}, }
@article {pmid33957682, year = {2021}, author = {Hartmann, P and Schnabl, B}, title = {New Developments in Microbiome in Alcohol-Associated and Nonalcoholic Fatty Liver Disease.}, journal = {Seminars in liver disease}, volume = {41}, number = {1}, pages = {87-102}, pmid = {33957682}, issn = {1098-8971}, support = {R01 AA020703/AA/NIAAA NIH HHS/United States ; National Institutes of Health//R01 AA020703/ ; National Institutes of Health//K12 HD85036/ ; I01 BX004594/BX/BLRD VA/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; National Institutes of Health//R01 AA24726/ ; National Institutes of Health//BX004594/ ; P50 AA011999/AA/NIAAA NIH HHS/United States ; Biomedical Laboratory Research &amp; Development Service of the VA Office of Research and Development//P50 AA011999/ ; Biomedical Laboratory Research &amp; Development Service of the VA Office of Research and Development//P30 DK120515/ ; U01 AA026939/AA/NIAAA NIH HHS/United States ; National Institutes of Health//U01 AA026939/ ; }, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Non-alcoholic Fatty Liver Disease/therapy ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {Alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are important causes of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of both ALD and NAFLD. Here we describe associated changes in the intestinal microbiota, and we detail randomized clinical trials in ALD and NAFLD which evaluate treatments modulating the intestinal microbiome including fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics. Finally, we discuss precision medicine approaches targeting the intestinal microbiome to ameliorate ALD and NAFLD.}, }
@article {pmid33953783, year = {2021}, author = {Chen, H and Yao, Y and Wang, W and Wang, D}, title = {Ge-Gen-Jiao-Tai-Wan Affects Type 2 Diabetic Rats by Regulating Gut Microbiota and Primary Bile Acids.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2021}, number = {}, pages = {5585952}, pmid = {33953783}, issn = {1741-427X}, abstract = {The Ge-Gen-Jiao-Tai-Wan (GGJTW) formula has been used to treat type 2 diabetes mellitus (T2DM) in China for a long time. Our previous study has proved that GGJTW could alleviate the type 2 diabetic symptoms, but the underlying mechanisms are still unclear. This study aimed to investigate the changes in gut microbiota and primary bile acids (PBAs) to determine the potential mechanisms of GGJTW in treating T2DM.The fecal transplant method and pseudogerm-free rats were used in our study.The16S rRNA gene sequencing method was used to analyze the changes in the intestinal flora, and PBAs in the colon contents were detected. Finally, the expression of farnesoid X receptor (FXR), G protein-coupled membrane receptor 5 (TGR5), and glucagon-like peptide-1 (GLP-1) was assessed. Following GGJTW treatment, we observed a decrease in blood glucose levels and improvements in glucose tolerance and serum lipid levels. Furthermore, we found that GGJTW could regulate the composition of the gut microbiota and upregulate the diabetic beneficial phylum Firmicutes and bile-acid-related genus Lactobacillus. PBAs in the colon contents were increased in the GGJTW-treated group, accompanied by upregulated expression of the bile acid receptors FXR and TGR5 and increased concentrations of GLP-1. These results indicated that GGJTW could alleviate symptoms of type 2 diabetic rats by regulating the gut microbiota, promoting the production of PBAs, and upregulating the PBA-FXR/TGR5-GLP-1 pathway.}, }
@article {pmid33953692, year = {2021}, author = {Smitka, K and Prochazkova, P and Roubalova, R and Dvorak, J and Papezova, H and Hill, M and Pokorny, J and Kittnar, O and Bilej, M and Tlaskalova-Hogenova, H}, title = {Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {613983}, pmid = {33953692}, issn = {1664-2392}, mesh = {*Autoantibodies ; Feeding and Eating Disorders/*immunology/microbiology ; Gastrointestinal Microbiome/*immunology ; Ghrelin/*immunology ; Humans ; Insulin/*immunology ; Leptin/*immunology ; Melanocyte-Stimulating Hormones/*immunology ; Neuropeptide Y/*immunology ; }, abstract = {The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.}, }
@article {pmid33952668, year = {2021}, author = {Lesniak, NA and Schubert, AM and Sinani, H and Schloss, PD}, title = {Clearance of Clostridioides difficile Colonization Is Associated with Antibiotic-Specific Bacterial Changes.}, journal = {mSphere}, volume = {6}, number = {3}, pages = {}, pmid = {33952668}, issn = {2379-5042}, support = {T32 AI007528/AI/NIAID NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; R01 GM099514/GM/NIGMS NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage/classification/*therapeutic use ; Bacteria/drug effects/*metabolism ; Cefoperazone/therapeutic use ; Clindamycin/therapeutic use ; Clostridioides difficile/*drug effects/*physiology ; Clostridium Infections/*drug therapy/microbiology/prevention &amp; control ; Disease Susceptibility ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/physiology ; Mice ; Streptomycin/therapeutic use ; }, abstract = {The gut bacterial community prevents many pathogens from colonizing the intestine. Previous studies have associated specific bacteria with clearing Clostridioides difficile colonization across different community perturbations. However, those bacteria alone have been unable to clear C. difficile colonization. To elucidate the changes necessary to clear colonization, we compared differences in bacterial abundance between communities able and unable to clear C. difficile colonization. We treated mice with titrated doses of antibiotics prior to C. difficile challenge, resulting in no colonization, colonization and clearance, or persistent colonization. Previously, we observed that clindamycin-treated mice were susceptible to colonization but spontaneously cleared C. difficile Therefore, we investigated whether other antibiotics would show the same result. We found that reduced doses of cefoperazone and streptomycin permitted colonization and clearance of C. difficile Mice that cleared colonization had antibiotic-specific community changes and predicted interactions with C. difficile Clindamycin treatment led to a bloom in populations related to Enterobacteriaceae Clearance of C. difficile was concurrent with the reduction of those blooming populations and the restoration of community members related to the Porphyromonadaceae and Bacteroides Cefoperazone created a susceptible community characterized by drastic reductions in the community diversity and interactions and a sustained increase in the abundance of many facultative anaerobes. Lastly, clearance in streptomycin-treated mice was associated with the recovery of multiple members of the Porphyromonadaceae, with little overlap in the specific Porphyromonadaceae observed in the clindamycin treatment. Further elucidation of how C. difficile colonization is cleared from different gut bacterial communities will improve C. difficile infection treatments.IMPORTANCE The community of microorganisms, or microbiota, in our intestines prevents pathogens like C. difficile from colonizing and causing infection. However, antibiotics can disturb the gut microbiota, which allows C. difficile to colonize. C. difficile infections (CDI) are primarily treated with antibiotics, which frequently leads to recurrent infections because the microbiota has not yet returned to a resistant state. The recurrent infection cycle often ends when the fecal microbiota from a presumed resistant person is transplanted into the susceptible person. Although this treatment is highly effective, we do not understand the mechanism. We hope to improve the treatment of CDI through elucidating how the bacterial community eliminates CDI. We found that C. difficile colonized susceptible mice but was spontaneously eliminated in an antibiotic treatment-specific manner. These data indicate that each community had different requirements for clearing colonization. Understanding how different communities clear colonization will reveal targets to improve CDI treatments.}, }
@article {pmid33947987, year = {2021}, author = {Panwar, RB and Sequeira, RP and Clarke, TB}, title = {Microbiota-mediated protection against antibiotic-resistant pathogens.}, journal = {Genes and immunity}, volume = {22}, number = {5-6}, pages = {255-267}, pmid = {33947987}, issn = {1476-5470}, support = {/WT_/Wellcome Trust/United Kingdom ; 107660/WT_/Wellcome Trust/United Kingdom ; 107660/Z/15Z//Wellcome Trust (Wellcome)/ ; }, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; *Clostridioides difficile ; Klebsiella pneumoniae ; *Microbiota ; }, abstract = {Colonization by the microbiota provides one of our most effective barriers against infection by pathogenic microbes. The microbiota protects against infection by priming immune defenses, by metabolic exclusion of pathogens from their preferred niches, and through direct antimicrobial antagonism. Disruption of the microbiota, especially by antibiotics, is a major risk factor for bacterial pathogen colonization. Restoration of the microbiota through microbiota transplantation has been shown to be an effective way to reduce pathogen burden in the intestine but comes with a number of drawbacks, including the possibility of transferring other pathogens into the host, lack of standardization, and potential disruption to host metabolism. More refined methods to exploit the power of the microbiota would allow us to utilize its protective power without the drawbacks of fecal microbiota transplantation. To achieve this requires detailed understanding of which members of the microbiota protect against specific pathogens and the mechanistic basis for their effects. In this review, we will discuss the clinical and experimental evidence that has begun to reveal which members of the microbiota protect against some of the most troublesome antibiotic-resistant pathogens: Klebsiella pneumoniae, vancomycin-resistant enterococci, and Clostridioides difficile.}, }
@article {pmid33947457, year = {2021}, author = {Xu, B and Qin, W and Yan, Y and Tang, Y and Zhou, S and Huang, J and Xie, C and Ma, L and Yan, X}, title = {Gut microbiota contributes to the development of endometrial glands in gilts during the ovary-dependent period.}, journal = {Journal of animal science and biotechnology}, volume = {12}, number = {1}, pages = {57}, pmid = {33947457}, issn = {1674-9782}, support = {2018CFA020//Natural Science Foundation of Hubei Province/ ; }, abstract = {BACKGROUND: The hyper-prolificacy Meishan gilts achieved a superior endometrial gland development (EGD) than white crossbred gilts during the ovary-independent period (before 60 d of age). Then, the EGD continues under the management of ovary-derived steroid hormones that regulated by gut microbiota (after 60 d of age). However, whether Meishan gilts' superiority in EGD lasting to the ovary-dependent period (after 60 d of age) and the role of gut microbiota in this period both remain unclear.<br><br>METHODS: Meishan gilts and Landrace x Yorkshire (LxY) gilts were raised under the same housing and feeding conditions until sexual maturity and then we&#xa0;compared their EGD and gut microbiota. Meanwhile, we transplanted fecal microbiota from Meishan gilts to L&#xd7;Y gilts to explore the role of gut microbiota in EGD. We sampled plasma every 3 weeks and collected the uterus, ovary, liver, and rectal feces after the sacrifice. We then determined the hormone concentrations and expressions of the EGD-related genes. We also profiled the gut microbiota using 16S rDNA sequencing and metabolites of plasma and liver tissue using untargeted metabolomics. Finally, the correlation analysis and significant test&#xa0;was conducted between FMT-shifted gut microbes and EGD-related indices.<br><br>RESULTS: Meishan gilts have larger endometrial gland area (P&#xa0;<&#x2009;0.001), longer uterine horn length (P&#xa0;<&#x2009;0.01) but lighter uterine horn weight (P&#xa0;<&#x2009;0.05), a distinctive gut microbiota compared with L&#xd7;Y gilts. Fecal microbiota transplantation (FMT) increased endometrial gland area (P&#xa0;<&#x2009;0.01). FMT markedly shifted the metabolite profiles of both liver and plasma, and these differential metabolites enriched in steroid hormone biosynthesis pathway. FMT increased estradiol and insulin-like growth factor 1 but decreased progesterone dynamically. FMT also increased the expression of the EGD-related genes estrogen receptor 1 gene, epithelial cadherin, and forkhead box protein A2. There is a significant correlation between FMT-shifted gut microbes and EGD-related indices.<br><br>CONCLUSION: Sexually matured Meishan gilts achieved a superior EGD than LxY gilts. Meanwhile, gut microbiota contribute to the EGD potentially via regulating of steroid hormones during the ovary-dependent period.}, }
@article {pmid33947304, year = {2021}, author = {Han, JX and Tao, ZH and Qian, Y and Yu, CY and Li, J and Kang, ZR and Lu, S and Xie, Y and Hong, J and Chen, H and Chen, YX and Fang, JY}, title = {ZFP90 drives the initiation of colitis-associated colorectal cancer via a microbiota-dependent strategy.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-20}, pmid = {33947304}, issn = {1949-0984}, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification ; Colitis-Associated Neoplasms/genetics/*metabolism/microbiology ; Disease Progression ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Repressor Proteins/genetics/*metabolism ; }, abstract = {Chronic inflammation and gut microbiota dysbiosis are risk factors for colorectal cancer. In clinical practice, patients with inflammatory bowel disease (IBD) have a greatly increased risk of developing colitis-associated colorectal cancer (CAC). However, the underlying mechanism of the initiation of CAC remains unknown. Systematic analyses using an existing genome-wide association study (GWAS) and conditional deletion of Zfp90 (encoding zinc finger protein 90 homolog) in a CAC mouse model indicated that Zfp90 is a putative oncogene in CAC development.Strikingly, depletion of the gut microbiota eliminated the tumorigenic effect of Zfp90 in the CAC mouse model. Moreover, fecal microbiota transplantation demonstrated that Zfp90 promoted CAC dependent on the gut microbiota. Analysis of 16s rDNA sequences in fecal specimens from the CAC mouse model allowed us to speculate that a Prevotella copri-defined microbiota might mediate the oncogenic role of Zfp90 in the development of CAC. Mechanistic studies revealed Zfp90 accelerated CAC development through the TLR4-PI3K-AKT-NF-κB pathway. Our findings revealed the crucial role of the Zfp90-microbiota-NF-κB axis in creating a tumor-promoting environment and suggested therapeutic targets for CAC prevention and treatment.}, }
@article {pmid33946843, year = {2021}, author = {Hrncir, T and Hrncirova, L and Kverka, M and Hromadka, R and Machova, V and Trckova, E and Kostovcikova, K and Kralickova, P and Krejsek, J and Tlaskalova-Hogenova, H}, title = {Gut Microbiota and NAFLD: Pathogenetic Mechanisms, Microbiota Signatures, and Therapeutic Interventions.}, journal = {Microorganisms}, volume = {9}, number = {5}, pages = {}, pmid = {33946843}, issn = {2076-2607}, support = {17-07332S//Czech Science Foundation/ ; 20-09732S//Czech Science Foundation/ ; 20-03997S//Czech Science Foundation/ ; NV19-03-00179//Ministry of Health of the Czech Republic/ ; NU20-04-00077//Ministry of Health of the Czech Republic/ ; RVO: 61388971//Institutional Research Concept/ ; PROGRES Q40/10//Charles University, Faculty of Medicine in Hradec Kralove/ ; FV40120//Technology Agency of the Czech Republic/ ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Its worldwide prevalence is rapidly increasing and is currently estimated at 24%. NAFLD is highly associated with many features of the metabolic syndrome, including obesity, insulin resistance, hyperlipidaemia, and hypertension. The pathogenesis of NAFLD is complex and not fully understood, but there is increasing evidence that the gut microbiota is strongly implicated in the development of NAFLD. In this review, we discuss the major factors that induce dysbiosis of the gut microbiota and disrupt intestinal permeability, as well as possible mechanisms leading to the development of NAFLD. We also discuss the most consistent NAFLD-associated gut microbiota signatures and immunological mechanisms involved in maintaining the gut barrier and liver tolerance to gut-derived factors. Gut-derived factors, including microbial, dietary, and host-derived factors involved in NAFLD pathogenesis, are discussed in detail. Finally, we review currently available diagnostic and prognostic methods, summarise latest knowledge on promising microbiota-based biomarkers, and discuss therapeutic strategies to manipulate the microbiota, including faecal microbiota transplantation, probiotics and prebiotics, deletions of individual strains with bacteriophages, and blocking the production of harmful metabolites.}, }
@article {pmid33946812, year = {2021}, author = {Kouidhi, S and Zidi, O and Alhujaily, M and Souai, N and Mosbah, A and Belali, TM and Ghedira, K and El Kossai, I and El Manaa, J and Mnif, W and Cherif, A}, title = {Fecal Metabolomics Reveals Distinct Profiles of Kidney Transplant Recipients and Healthy Controls.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, pmid = {33946812}, issn = {2075-4418}, abstract = {Monitoring graft recipients remains dependent on traditional biomarkers and old technologies lacking specificity, sensitivity, or accuracy. Recently, metabolomics is becoming a promising approach that may offer to kidney transplants a more effective and specific monitoring. Furthermore, emerging evidence suggested a fundamental role of gut microbiota as an important determinant of patients' metabolomes. In the current study, we enrolled forty stable renal allografts recipients compared to twenty healthy individuals. Samples were taken at different time points from patient to patient following transplantation surgery, which varied from 3 months to 22 years post-graft. All patients started the immunosuppression therapy immediately following kidney graft (Day 0). Gas chromatography-mass spectrometry (GC-MS) was employed to perform untargeted analysis of fecal metabolites. Globally, the fecal metabolic signature was significantly different between kidney transplants and the control group. Fecal metabolome was dominated by lipids (sterols and fatty acids) in the stable transplant group compared to the controls (p < 0.05). Overall, 18 metabolites were significantly altered within kidney transplant recipients. Furthermore, the most notable altered metabolic pathways in kidney transplants include ubiquinone and other terpenoid-quinone biosynthesis, tyrosine metabolism, tryptophan biosynthesis, and primary bile acid biosynthesis. Fecal metabolites could effectively distinguish stable transplant recipients from controls, supporting the potential utility of metabolomics in rapid and non-invasive diagnosis to produce relevant biomarkers and to help clinicians in monitoring kidney transplants. Further investigations are needed to clarify the physiological relevance of fecal metabolome and to assess the impact of microbiota modulation.}, }
@article {pmid33946610, year = {2021}, author = {Karaduta, O and Dvanajscak, Z and Zybailov, B}, title = {Metaproteomics-An Advantageous Option in Studies of Host-Microbiota Interaction.}, journal = {Microorganisms}, volume = {9}, number = {5}, pages = {}, pmid = {33946610}, issn = {2076-2607}, support = {P20GM121293//NIH Center of Biomedical Research Excellence/ ; }, abstract = {Gut microbiome contributes to host health by maintaining homeostasis, increasing digestive efficiency, and facilitating the development of the immune system. Manipulating gut microbiota is being recognized as a therapeutic target to manage various chronic diseases. The therapeutic manipulation of the intestinal microbiome is achieved through diet modification, the administration of prebiotics, probiotics, or antibiotics, and more recently, fecal microbiome transplantation (FMT). In this opinion paper, we give a perspective on the current status of application of multi-omics technologies in the analysis of host-microbiota interactions. The aim of this paper was to highlight the strengths of metaproteomics, which integrates with and often relies on other approaches.}, }
@article {pmid33938391, year = {2021}, author = {Rubio-Del-Campo, A and Gozalbo-Rovira, R and Moya-Gonzálvez, EM and Alberola, J and Rodríguez-Díaz, J and Yebra, MJ}, title = {Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-20}, pmid = {33938391}, issn = {1949-0984}, mesh = {Acetates/metabolism ; Adult ; Animals ; Bacteria/classification/genetics/isolation &amp; purification/*metabolism ; Butyrates/metabolism ; DNA, Bacterial/genetics ; Disaccharides/analysis/*metabolism ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Male ; Mice ; Mice, Inbred C57BL ; Milk, Human/chemistry/*metabolism ; RNA, Ribosomal, 16S/genetics ; Young Adult ; }, abstract = {Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-α1,3-GlcNAc (3FN), fucosyl-α1,6-GlcNAc, lacto-N-biose (LNB) and galacto-N-biose on the fecal microbiota and host-microbiota interactions. 16S rRNA amplicon sequencing showed that certain bacterial genera significantly increased (Ruminococcus and Oscillospira) or decreased (Eubacterium and Clostridium) in all disaccharide-supplemented groups. Interestingly, cluster analysis differentiates the consumption of fucosyl-oligosaccharides from galactosyl-oligosaccharides, highlighting the disappearance of Akkermansia genus in both fucosyl-oligosaccharides. An increment of the relative abundance of Coprococcus genus was only observed with 3FN. As well, LNB significantly increased the relative abundance of Bifidobacterium, whereas the absolute levels of this genus, as measured by quantitative real-time PCR, did not significantly increase. OTUs corresponding to the species Bifidobacterium longum, Bifidobacterium adolescentis and Ruminococcus gnavus were not present in the control after the 3-week intervention, but were shared among the donor and specific disaccharide groups, indicating that their survival is dependent on disaccharide supplementation. The 3FN-feeding group showed increased levels of butyrate and acetate in the colon, and decreased levels of serum HDL-cholesterol. 3FN also down-regulated the pro-inflammatory cytokine TNF-α and up-regulated the anti-inflammatory cytokines IL-10 and IL-13, and the Toll-like receptor 2 in the large intestine tissue. The present study revealed that the four disaccharides show efficacy in producing beneficial compositional shifts of the gut microbiota and in addition, the 3FN demonstrated physiological and immunomodulatory roles.}, }
@article {pmid33938243, year = {2021}, author = {Sari, G and van Oord, GW and van de Garde, MDB and Voermans, JJC and Boonstra, A and Vanwolleghem, T}, title = {Sexual Dimorphism in Hepatocyte Xenograft Models.}, journal = {Cell transplantation}, volume = {30}, number = {}, pages = {9636897211006132}, pmid = {33938243}, issn = {1555-3892}, mesh = {Animals ; Disease Models, Animal ; Hepatocytes/*transplantation ; Humans ; Male ; Mice ; Mice, SCID ; Mice, Transgenic ; *Sex Characteristics ; Xenograft Model Antitumor Assays ; }, abstract = {Humanized liver mouse models are crucial tools in liver research, specifically in the fields of liver cell biology, viral hepatitis and drug metabolism. The livers of these humanized mouse models are repopulated by 3-dimensional islands of fully functional primary human hepatocytes (PHH), which are notoriously difficult to maintain in vitro. As low efficiency and high cost hamper widespread use, optimization is of great importance. In the present study, we analyzed experimental factors associated with Hepatitis E virus (HEV) infection and PHH engraftment in 2 xenograft systems on a Nod-SCID-IL2Ry[-/-] background: the alb-urokinase plasminogen activator mouse model (uPA-NOG, n=399); and the alb-HSV thymidine kinase model (TK-NOG, n = 198). In a first analysis, HEV fecal shedding in liver humanized uPA-NOG and TK-NOG mice with comparable human albumin levels was found to be similar irrespective of the mouse genetic background. In a second analysis, sex, mouse age at transplantation and hepatocyte donor were the most determinant factors for xenograft success in both models. The sexual imbalance for xenograft success was related to higher baseline ALT levels and lower thresholds for ganciclovir induced liver morbidity and mortality in males. These data call for sexual standardization of human hepatocyte xenograft models, but also provide a platform for further studies on mechanisms behind sexual dimorphism in liver diseases.}, }
@article {pmid33937093, year = {2021}, author = {Li, Y and Xia, S and Jiang, X and Feng, C and Gong, S and Ma, J and Fang, Z and Yin, J and Yin, Y}, title = {Gut Microbiota and Diarrhea: An Updated Review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {625210}, pmid = {33937093}, issn = {2235-2988}, mesh = {Animals ; Diarrhea ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Probiotics ; }, abstract = {Diarrhea is a common problem to the whole world and the occurrence of diarrhea is highly associated with gut microbiota, such as bacteria, fungi, and viruses. Generally, diarrheal patients or animals are characterized by gut microbiota dysbiosis and pathogen infections may lead to diarrheal phenotypes. Of relevance, reprograming gut microbiota communities by dietary probiotics or fecal bacteria transplantation are widely introduced to treat or prevent diarrhea. In this review, we discussed the influence of the gut microbiota in the infection of diarrhea pathogens, and updated the research of reshaping the gut microbiota to prevent or treat diarrhea for the past few years. Together, gut microbiota manipulation is of great significance to the prevention and treatment of diarrhea, and further insight into the function of the gut microbiota will help to discover more anti-diarrhea probiotics.}, }
@article {pmid33937092, year = {2021}, author = {Chen, J and Zaman, A and Ramakrishna, B and Olesen, SW}, title = {Stool Banking for Fecal Microbiota Transplantation: Methods and Operations at a Large Stool Bank.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {622949}, pmid = {33937092}, issn = {2235-2988}, mesh = {*Clostridium Infections/therapy ; Donor Selection ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Tissue Donors ; }, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of microbiota-mediated indications. Stool banks centralize FMT donor screening and FMT material preparation with the goal of expanding access to FMT material while simultaneously improving its safety, quality, and convenience. Although there are published consensuses on donor screening guidelines, there are few reports about the implementation of those guidelines in functioning stool banks.<br><br>METHODS: To help inform consensus standards with data gathered from real-world settings and, in turn, to improve patient care, here we describe the general methodology used in 2018 by OpenBiome, a large stool bank, and its outputs in that year.<br><br>RESULTS: In 2018, the stool bank received 7,536 stool donations from 210 donors, a daily average of 20.6 donations, and processed 4,271 of those donations into FMT preparations. The median time a screened and enrolled stool donor actively donated stool was 5.8 months. The median time between the manufacture of an FMT preparation and its shipment to a hospital or physician was 8.9 months. Half of the stool bank's partner hospitals and physicians ordered an average of 0.75 or fewer FMT preparations per month.<br><br>CONCLUSIONS: Further knowledge sharing should help inform refinements of stool banking guidelines and best practices.}, }
@article {pmid33935016, year = {2021}, author = {Eisele, Y and Mallea, PM and Gigic, B and Stephens, WZ and Warby, CA and Buhrke, K and Lin, T and Boehm, J and Schrotz-King, P and Hardikar, S and Huang, LC and Pickron, TB and Scaife, CL and Viskochil, R and Koelsch, T and Peoples, AR and Pletneva, MA and Bronner, M and Schneider, M and Ulrich, AB and Swanson, EA and Toriola, AT and Shibata, D and Li, CI and Siegel, EM and Figueiredo, J and Janssen, KP and Hauner, H and Round, J and Ulrich, CM and Holowatyj, AN and Ose, J}, title = {Fusobacterium nucleatum and Clinicopathologic Features of Colorectal Cancer: Results From the ColoCare Study.}, journal = {Clinical colorectal cancer}, volume = {20}, number = {3}, pages = {e165-e172}, pmid = {33935016}, issn = {1938-0674}, support = {UL1 TR002538/TR/NCATS NIH HHS/United States ; R01 CA189184/CA/NCI NIH HHS/United States ; KL2 TR002539/TR/NCATS NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; T32 HG008962/HG/NHGRI NIH HHS/United States ; K12 HD043483/HD/NICHD NIH HHS/United States ; R01 CA211705/CA/NCI NIH HHS/United States ; P30 CA042014/CA/NCI NIH HHS/United States ; R01 CA207371/CA/NCI NIH HHS/United States ; K07 CA222060/CA/NCI NIH HHS/United States ; }, mesh = {*Colorectal Neoplasms ; *Fusobacterium nucleatum ; Humans ; Microsatellite Instability ; Prognosis ; Prospective Studies ; }, abstract = {BACKGROUND: Fusobacterium nucleatum (Fn), a bacterium associated with a wide spectrum of infections, has emerged as a key microbe in colorectal carcinogenesis. However, the underlying mechanisms and clinical relevance of Fn in colorectal cancer (CRC) remain incompletely understood.<br><br>PATIENTS AND METHODS: We examined associations between Fn abundance and clinicopathologic characteristics among 105 treatment-na&#xef;ve CRC patients enrolled in the international, prospective ColoCare Study. Electronic medical charts, including pathological reports, were reviewed to document clinicopathologic features. Quantitative real-time polymerase chain reaction (PCR) was used to amplify/detect Fn DNA in preoperative fecal samples. Multinomial logistic regression was used to analyze associations between Fn abundance and patient sex, age, tumor stage, grade, site, microsatellite instability, body mass index (BMI), alcohol consumption, and smoking history. Cox proportional hazards models were used to investigate associations of Fn abundance with overall survival in adjusted models.<br><br>RESULTS: Compared to patients with undetectable or low Fn abundance, patients with high Fn abundance (n&#xa0;=&#xa0;22) were 3-fold more likely to be diagnosed with rectal versus colon cancer (odds ratio [OR]&#xa0;=&#xa0;3.01; 95% confidence interval [CI], 1.06-8.57; P = .04) after adjustment for patient sex, age, BMI, and study site. Patients with high Fn abundance also had a 5-fold increased risk of being diagnosed with rectal cancer versus right-sided colon cancer (OR&#xa0;=&#xa0;5.32; 95% CI, 1.23-22.98; P&#xa0;=&#xa0;.03). There was no statistically significant association between Fn abundance and overall survival.<br><br>CONCLUSION: Our findings suggest that Fn abundance in fecal samples collected prior to surgery varies by tumor site among treatment-na&#xef;ve CRC patients. Overall, fecal Fn abundance may have diagnostic and prognostic significance in the clinical management of CRC.}, }
@article {pmid33934412, year = {2021}, author = {Goeser, F and Sifft, B and Stein-Thoeringer, C and Farowski, F and Strassburg, CP and Brossart, P and Higgins, PG and Scheid, C and Wolf, D and Holderried, TAW and Vehreschild, MJGT and Cruz Aguilar, MR}, title = {Fecal microbiota transfer for refractory intestinal graft-versus-host disease - Experience from two German tertiary centers.}, journal = {European journal of haematology}, volume = {107}, number = {2}, pages = {229-245}, doi = {10.1111/ejh.13642}, pmid = {33934412}, issn = {1600-0609}, mesh = {Adult ; Aged ; Biodiversity ; Disease Management ; *Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Diseases/diagnosis/*etiology/*therapy ; Gastrointestinal Microbiome ; Germany ; Graft vs Host Disease/diagnosis/*etiology/*therapy ; Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Humans ; Male ; Middle Aged ; Tertiary Care Centers ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {RATIONALE: Steroid refractory graft-vs-host disease (sr-GvHD) represents a challenging complication after allogeneic hematopoietic cell transplantation (allo-HCT). Intestinal microbiota (IM) diversity and dysbiosis were identified as influencing factors for the development of acute GvHD. Fecal microbiota transfer (FMT) is hypothesized to restore IM dysbiosis, but there is limited knowledge about the significance of FMT in the treatment of sr-GvHD.<br><br>OBJECTIVES: We studied the effects of FMT on sr-GvHD in allo-HCT patients from two German tertiary clinical centers (n&#xa0;=&#xa0;11 patients; period: March 2017 until July 2019). To assess safety and clinical efficacy, we analyzed clinical data pre- and post-FMT (day -14 to +30 relative to FMT). Moreover, IM were analyzed in donor samples and in a subset of patients pre- and post-FMT by 16S rRNA sequencing.<br><br>RESULTS: Post-FMT, we observed no intervention-associated, systemic inflammatory responses and only minor side effects (5/11 patients: abdominal pain and transformation of peristalsis-each 3/11 and vomiting-1/11). Stool frequencies and volumes were significantly reduced [pre- vs post-FMT (d14): P&#xa0;<&#xa0;.05, respectively] as well as clear attenuation regarding both grading and staging of sr-GvHD was present upon FMT. Moreover, IM analyses revealed an increase of alpha diversity as well as a compositional shifts toward the donor post-FMT.<br><br>CONCLUSIONS: In our study, we observed positive effects on sr-GVHD after FMT without the occurrence of major adverse events. Although these findings are in line with published data on beneficial effects of FMT in sr-GvHD, further randomized clinical studies are urgently needed to better define the clinical validity including mode of action.}, }
@article {pmid33931880, year = {2021}, author = {de la Visitación, N and Robles-Vera, I and Toral, M and Gómez-Guzmán, M and Sánchez, M and Moleón, J and González-Correa, C and Martín-Morales, N and O'Valle, F and Jiménez, R and Romero, M and Duarte, J}, title = {Gut microbiota contributes to the development of hypertension in a genetic mouse model of systemic lupus erythematosus.}, journal = {British journal of pharmacology}, volume = {178}, number = {18}, pages = {3708-3729}, doi = {10.1111/bph.15512}, pmid = {33931880}, issn = {1476-5381}, mesh = {Animals ; Disease Models, Animal ; Female ; *Gastrointestinal Microbiome ; Humans ; *Hypertension ; Kidney ; *Lupus Erythematosus, Systemic ; Mice ; Rabbits ; }, abstract = {BACKGROUND AND PURPOSE: Hypertension is an important cardiovascular risk factor that is prevalent in the systemic lupus erythematosus patient population. Here, we have investigated whether intestinal microbiota is involved in hypertension in a genetic mouse model of systemic lupus erythematosus.<br><br>EXPERIMENTAL APPROACH: Twenty-six-week-old female NZW/LacJ (control) and NZBWF1 (F1 hybrid of New Zealand Black and New Zealand White strains; systemic lupus erythematosus) mice were treated for 6&#x2009;weeks with a broad-spectrum antibiotic mixture or with vancomycin. Faecal microbiota transplantation was performed from donor systemic lupus erythematosus group to recipient to germ-depleted or germ-free mice.<br><br>KEY RESULTS: Antibiotic treatment inhibited the development of hypertension and renal injury, improved endothelial dysfunction and vascular oxidative stress, and decreased aortic Th17 infiltration in NZBWF1 mice. High BP and vascular complications found in systemic lupus erythematosus mice, but not autoimmunity, kidney inflammation and endotoxemia, were reproduced by the transfer of gut microbiota from systemic lupus erythematosus donors to germ-free or germ-depleted mice. Increased proportions of Bacteroides were linked with high BP in these mice. The reduced endothelium-dependent vasodilator responses to acetylcholine and the high BP induced by microbiota from hypertensive systemic lupus erythematosus mice were inhibited after IL-17 neutralization.<br><br>CONCLUSION AND IMPLICATIONS: Changes in T-cell populations, endothelial function, vascular inflammation and hypertension driven by a genetic systemic lupus erythematosus background can be modified by antibiotic-induced changes in gut microbiota. The vascular changes induced by hypertensive systemic lupus erythematosus microbiota were mediated by Th17 infiltration in the vasculature.}, }
@article {pmid33928675, year = {2021}, author = {Chen, L and Wu, N and Kennedy, L and Francis, H and Ceci, L and Zhou, T and Samala, N and Kyritsi, K and Wu, C and Sybenga, A and Ekser, B and Dar, W and Atkins, C and Meadows, V and Glaser, S and Alpini, G}, title = {Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes.}, journal = {Hepatology (Baltimore, Md.)}, volume = {74}, number = {4}, pages = {1845-1863}, pmid = {33928675}, issn = {1527-3350}, support = {R01 DK108959/DK/NIDDK NIH HHS/United States ; R01 DK121330/DK/NIDDK NIH HHS/United States ; R01 DK110035/DK/NIDDK NIH HHS/United States ; R01 DK107310/DK/NIDDK NIH HHS/United States ; I01 BX000574/BX/BLRD VA/United States ; I01 BX003031/BX/BLRD VA/United States ; IK6 BX004601/BX/BLRD VA/United States ; R01 DK119421/DK/NIDDK NIH HHS/United States ; IK6 BX005226/BX/BLRD VA/United States ; R21 AA025997/AA/NIAAA NIH HHS/United States ; R01 DK122796/DK/NIDDK NIH HHS/United States ; I01 BX001724/BX/BLRD VA/United States ; R01 DK076898/DK/NIDDK NIH HHS/United States ; R01 DK115184/DK/NIDDK NIH HHS/United States ; R01 AA028711/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Bile Ducts/cytology/metabolism ; Cell Line ; Cellular Senescence/genetics ; Disease Models, Animal ; Fatty Acid Elongases/genetics/metabolism ; Fatty Acids, Nonesterified ; Hepatocytes/metabolism ; Humans ; Lipogenesis/genetics ; Mice ; Mice, Knockout ; MicroRNAs/genetics/metabolism ; Non-alcoholic Fatty Liver Disease/*genetics/metabolism ; Phenotype ; Receptors, G-Protein-Coupled/*genetics/metabolism ; Receptors, Gastrointestinal Hormone/*genetics/metabolism ; Secretin/*genetics/metabolism ; Up-Regulation ; }, abstract = {BACKGROUND AND AIMS: Human NAFLD is characterized at early stages by hepatic steatosis, which may progress to NASH when the liver displays microvesicular steatosis, lobular inflammation, and pericellular fibrosis. The secretin (SCT)/secretin receptor (SCTR) axis promotes biliary senescence and liver fibrosis in cholestatic models through down-regulation of miR-125b signaling. We aim to evaluate the effect of disrupting biliary SCT/SCTR/miR-125b signaling on hepatic steatosis, biliary senescence, and liver fibrosis in NAFLD/NASH.<br><br>APPROACH AND RESULTS: In vivo, 4-week-old male wild-type, Sct[-/-] and Sctr[-/-] mice were fed a control diet or high-fat diet (HFD) for 16 weeks. The expression of SCT/SCTR/miR-125b axis was measured in human NAFLD/NASH liver samples and HFD mouse livers by immunohistochemistry and quantitative PCR. Biliary/hepatocyte senescence, ductular reaction, and liver angiogenesis were evaluated in mouse liver and human NAFLD/NASH liver samples. miR-125b target lipogenesis genes in hepatocytes were screened and validated by custom RT[2] Profiler PCR array and luciferase assay. Biliary SCT/SCTR expression was increased in human NAFLD/NASH samples and in livers of HFD mice, whereas the expression of miR-125b was decreased. Biliary/hepatocyte senescence, ductular reaction, and liver angiogenesis were observed in human NAFLD/NASH samples as well as HFD mice, which were decreased in Sct[-/-] and Sctr[-/-] HFD mice. Elovl1 is a lipogenesis gene targeted by miR-125b, and its expression was also decreased in HFD mouse hepatocytes following Sct or Sctr knockout. Bile acid profile in fecal samples have the greatest changes between wild-type mice and Sct[-/-] /Sctr[-/-] mice.<br><br>CONCLUSION: The biliary SCT/SCTR/miR-125b axis promotes liver steatosis by up-regulating lipid biosynthesis gene Elovl1. Targeting the biliary SCT/SCTR/miR-125b axis may be key for ameliorating phenotypes of human NAFLD/NASH.}, }
@article {pmid33928112, year = {2021}, author = {Wu, C and Lyu, W and Hong, Q and Zhang, X and Yang, H and Xiao, Y}, title = {Gut Microbiota Influence Lipid Metabolism of Skeletal Muscle in Pigs.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {675445}, pmid = {33928112}, issn = {2296-861X}, abstract = {Gut microbiota is recognized as a strong determinant of host physiology including fat metabolism and can transfer obesity-associated phenotypes from donors to recipients. However, the relationship between gut microbiota and intramuscular fat (IMF) is still largely unknown. Obese Jinhua pigs (JP) have better meat quality that is associated with higher IMF content than lean Landrace pigs (LP). The present study was conducted to test the contribution of gut microbiota to IMF properties by transplanting fecal microbiota of adult JP and LP to antibiotics-treated mice. Similar to JP donors, the mice receiving JP's microbiota (JM) had elevated lipid and triglyceride levels and the lipoprotein lipase activity, as well as reduced mRNA level of angiopoietin-like 4 (ANGPTL4) in the gastrocnemius muscles, compared to those in mice receiving LP's microbiota (LM). High-throughput 16S rRNA sequencing confirmed that transplantation of JP and LP feces differently reconstructed the gut microbiota in both jejunum and colon of mouse recipients. In colonic samples, we observed an elevated ratio of Firmicutes to Bacteroidetes and increased abundance of genus Romboutsia in JM, which were positively correlated with obesity. Furthermore, the abundance of Akkermansia decreased in JM, which is positively correlated with lean. Colonic concentrations of acetate (P = 0.047) and butyrate (P = 0.014) were significantly lower in JM than in LM, and consistently, the terminal genes for butyrate synthesis, butyryl CoA: acetate CoA transferase were less abundant in colonic microbiota of JM. Taken together, these gut microbiota of obese JP intrinsically promotes IMF accumulation and can transfer the properties to mouse recipients. Manipulation of intestinal microbiota will, therefore, have the potential to improve the meat quality and flavor of pigs and even to ameliorate the metabolic syndrome in human.}, }
@article {pmid33928033, year = {2021}, author = {Li, W and Deng, X and Chen, T}, title = {Exploring the Modulatory Effects of Gut Microbiota in Anti-Cancer Therapy.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {644454}, pmid = {33928033}, issn = {2234-943X}, abstract = {In the recent decade, gut microbiota has received growing interest due to its role in human health and disease. On the one hand, by utilizing the signaling pathways of the host and interacting with the immune system, the gut microbiota is able to maintain the homeostasis in human body. This important role is mainly modulated by the composition of microbiota, as a normal microbiota composition is responsible for maintaining the homeostasis of human body, while an altered microbiota profile could contribute to several pathogenic conditions and may further lead to oncogenesis and tumor progression. Moreover, recent insights have especially focused on the important role of gut microbiota in current anticancer therapies, including chemotherapy, radiotherapy, immunotherapy and surgery. Research findings have indicated a bidirectional interplay between gut microbiota and these therapeutic methods, in which the implementation of different therapeutic methods could lead to different alterations in gut microbiota, and the presence of gut microbiota could in turn contribute to different therapeutic responses. As a result, manipulating the gut microbiota to reduce the therapy-induced toxicity may provide an adjuvant therapy to achieve a better therapeutic outcome. Given the complex role of gut microbiota in cancer treatment, this review summarizes the interactions between gut microbiota and anticancer therapies, and demonstrates the current strategies for reshaping gut microbiota community, aiming to provide possibilities for finding an alternative approach to lower the damage and improve the efficacy of cancer therapy.}, }
@article {pmid33927926, year = {2021}, author = {Scibelli, N and Singh, P and Raynor, K}, title = {Intestinal Dysbiosis Disguised as a Rectal Fistula Treated With Autologous Fecal Microbiota Transplantation.}, journal = {Cureus}, volume = {13}, number = {3}, pages = {e14115}, pmid = {33927926}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) has been efficacious in the treatment of intestinal dysbiosis, derangement of the native intestinal microflora, and the indications for autologous FMT are growing. A 69-year-old Caucasian man with a past medical history of paraplegia secondary to motor vehicle accident and sigmoid-end colostomy presented to his gastroenterologist with the complaint of rectal discharge. A complicated medical course pre-dated his presentation and included multiple decubitus ulcers requiring debridement and several courses of broad-spectrum antibiotics. The rectal discharge was initially presumed to be from a fistula leading to one of his ulcers; however, workup with anoscopy, flexible sigmoidoscopy, and magnetic resonance imaging of the pelvis showed no visible perirectal abscess or connection to the sigmoid colon through a fistula. Intestinal dysbiosis was an alternative theory considered to be the cause of his copious rectal discharge due to his several courses of broad-spectrum antibiotics and prolonged inactivity of his gut. This prompted a trial treatment plan utilizing autologous FMT, with the patient administering enemas containing his own stool to the distal limb of his bowel. As a result of this treatment, the patient's chief complaint completely resolved within days of initiating treatment, although symptoms did eventually return. We would like to propose that further randomized studies should be done to investigate autologous FMT as a treatment for patients suffering from intestinal dysbiosis following sigmoid-end colostomy.}, }
@article {pmid33926922, year = {2021}, author = {Kragsnaes, MS and Kjeldsen, J and Horn, HC and Munk, HL and Pedersen, JK and Just, SA and Ahlquist, P and Pedersen, FM and de Wit, M and Möller, S and Andersen, V and Kristiansen, K and Kinggaard Holm, D and Holt, HM and Christensen, R and Ellingsen, T}, title = {Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial.}, journal = {Annals of the rheumatic diseases}, volume = {80}, number = {9}, pages = {1158-1167}, doi = {10.1136/annrheumdis-2020-219511}, pmid = {33926922}, issn = {1468-2060}, mesh = {Adult ; Antirheumatic Agents/therapeutic use ; Arthritis, Psoriatic/microbiology/*therapy ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Methotrexate/therapeutic use ; Middle Aged ; Proof of Concept Study ; Treatment Outcome ; }, abstract = {OBJECTIVES: Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA).<br><br>METHODS: In this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (&#x2265;3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26.<br><br>RESULTS: Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)).<br><br>CONCLUSIONS: In this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA.<br><br>TRIAL REGISTRATION NUMBER: NCT03058900.}, }
@article {pmid33926254, year = {2021}, author = {Zhang, L and Ma, X and Liu, P and Ge, W and Hu, L and Zuo, Z and Xiao, H and Liao, W}, title = {Treatment and mechanism of fecal microbiota transplantation in mice with experimentally induced ulcerative colitis.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {246}, number = {13}, pages = {1563-1575}, pmid = {33926254}, issn = {1535-3699}, mesh = {Akkermansia/isolation &amp; purification/pathogenicity ; Animals ; Colitis, Ulcerative/etiology/microbiology/*therapy ; Colon/metabolism/microbiology ; Dextran Sulfate/toxicity ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Helicobacter/isolation &amp; purification/pathogenicity ; Interleukins/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes/metabolism ; Transforming Growth Factor beta/metabolism ; }, abstract = {Restoring intestinal microbiota dysbiosis with fecal microbiota transplantation is considered as a promising treatment for ulcerative colitis. However, the mechanisms underlying its relieving effects remain unclear. Ulcerative colitis pathogenesis is associated with the involvement of immune cells and inflammatory cytokines. Here, we aimed to investigate the effect of fecal microbiota transplantation on T cell cytokines in a dextran sulfate sodium-induced ulcerative colitis mouse model. Five-aminosalicylic acid (5-ASA) was used as the positive control. Male C57BL/6 mice were randomly assigned to control, model (UC), UC + FMT, and UC + 5-ASA groups. Each group consisted of five mice. The establishment of the mouse model was verified by fecal occult-blood screening and hematoxylin-eosin staining. Results showed that fecal microbiota transplantation reduced colonic inflammation, significantly decreased T helper (Th)1 and Th17 cells, interferon-gamma, interleukin-2 and interleukin-17, as well as significantly increased Th2 and regulatory T (Treg) cells, interleukin-4, interleukin-10, and transforming growth factor-beta, and improved routine blood count. Furthermore, 16S rRNA gene-sequencing analysis showed a significant increase in the relative abundance of genus Akkermansia and a significant decrease in the relative abundance of genus Helicobacter in the ulcerative colitis group. Fecal microbiota transplantation restored the profile of the intestinal microbiota to that of the control group. These findings demonstrated the capability of fecal microbiota transplantation in controlling experimentally induced ulcerative colitis by improving Th1/Th2 and Th17/Treg imbalance through the regulation of intestinal microbiota.}, }
@article {pmid33926088, year = {2021}, author = {Polak, K and Bergler-Czop, B and Szczepanek, M and Wojciechowska, K and Frątczak, A and Kiss, N}, title = {Psoriasis and Gut Microbiome-Current State of Art.}, journal = {International journal of molecular sciences}, volume = {22}, number = {9}, pages = {}, pmid = {33926088}, issn = {1422-0067}, mesh = {Bacterial Translocation ; Bacteroidetes ; Cardiovascular Diseases/microbiology ; Dysbiosis/physiopathology ; Firmicutes ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Inflammatory Bowel Diseases/microbiology ; Microbiota ; Probiotics/therapeutic use ; Psoriasis/*metabolism/*microbiology ; }, abstract = {Psoriasis is a chronic, immune-mediated inflammatory disease that affects around 125 million people worldwide. Several studies concerning the gut microbiota composition and its role in disease pathogenesis recently demonstrated significant alterations among psoriatic patients. Certain parameters such as Firmicutes/Bacteroidetes ratio or Psoriasis Microbiome Index were developed in order to distinguish between psoriatic and healthy individuals. The "leaky gut syndrome" and bacterial translocation is considered by some authors as a triggering factor for the onset of the disease, as it promotes chronic systemic inflammation. The alterations were also found to resemble those in inflammatory bowel diseases, obesity and certain cardiovascular diseases. Microbiota dysbiosis, depletion in SCFAs production, increased amount of produced TMAO, dysregulation of the pathways affecting the balance between lymphocytes populations seem to be the most significant findings concerning gut physiology in psoriatic patients. The gut microbiota may serve as a potential response-to-treatment biomarker in certain cases of biological treatment. Oral probiotics administration as well as fecal microbial transplantation were most reported in bringing health benefits to psoriatic patients. However, the issue of psoriatic bacterial gut composition, its role and healing potential needs further investigation. Here we reviewed the literature on the current state of the relationship between psoriasis and gut microbiome.}, }
@article {pmid33924834, year = {2021}, author = {Clancy, AK and Lee, C and Hamblin, H and Gunaratne, AW and LeBusque, A and Beck, EJ and Dawson, MV and Borody, TJ}, title = {Dietary Intakes of Recipients of Faecal Microbiota Transplantation: An Observational Pilot Study.}, journal = {Nutrients}, volume = {13}, number = {5}, pages = {}, pmid = {33924834}, issn = {2072-6643}, mesh = {Adolescent ; Adult ; Diet/*methods ; *Diet Records ; *Fecal Microbiota Transplantation ; Female ; Humans ; Irritable Bowel Syndrome/*therapy ; Male ; Middle Aged ; Nutrients/*administration &amp; dosage ; Pilot Projects ; Prospective Studies ; Recommended Dietary Allowances ; Surveys and Questionnaires ; Young Adult ; }, abstract = {This study reports on the dietary intake of recipients of faecal microbiota transplantation (FMT), comparing this with dietary guidelines, and investigates the relationship between dietary intake and clinical outcomes. Males and females aged ≥ 16 years with irritable bowel syndrome or inflammatory bowel disease undergoing FMT were invited to complete validated symptom and quality of life (QOL) questionnaires and three-day weighed food diaries. Descriptive statistics were calculated for symptom scores, QOL scores, nutrients, and food group servings, and compared to Australian population norms, nutrient reference values, and dietary guidelines. The relationship between dietary intake, symptoms, and QOL was assessed. Participants (n = 18) reported baseline symptoms of urgency, abdominal pain, nausea, and bloating and reduced QOL. Of the participants who completed food diaries, 8/14 met the recommended 30 g of fibre when including supplements. Participants met the recommendations for micronutrients and food groups except calcium, fruit, and dairy/dairy alternatives. There was a non-significant trend towards lower symptom severity scores in participants who met the fibre target. The high degree of variability in participant fibre intakes highlights diet as a key variable that has not been previously controlled for in FMT intervention studies. Future studies examining FMT should include dietary analysis of habitual intake of the recipients and donors.}, }
@article {pmid33923423, year = {2021}, author = {Portenkirchner, C and Kienle, P and Horisberger, K}, title = {Checkpoint Inhibitor-Induced Colitis-A Clinical Overview of Incidence, Prognostic Implications and Extension of Current Treatment Options.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {33923423}, issn = {1424-8247}, abstract = {In recent years, anti-tumor immunotherapies have witnessed a major breakthrough with the emergence of immune checkpoint inhibitors (ICIs). However, the use of ICIs has also brought an era of a certain class of adverse events that differ from those of classical chemotherapies and are more reminiscent of autoimmune diseases. This article focuses exclusively on colitis as an irAE with emphasis on vulnerable patient groups, the prognostic significance of colitis, treatment, and new therapeutic approaches that may be applicable. Colitis itself is associated with a favorable oncological outcome of the underlying disease but is as well the most common irAE leading to discontinuation of therapy. Especially in vulnerable patient groups such as IBD patients and elderly patients, colitis occurs more frequently as a side effect. It is precisely in these two patient groups that side effects more often lead to discontinuation of therapy. Therefore, in addition to the current therapy of colitis through immunosuppression, the focus should also be on new forms of therapy of severe colitis, such as fecal transplantation or ileostomy creation.}, }
@article {pmid33920646, year = {2021}, author = {Nomura, K and Ishikawa, D and Okahara, K and Ito, S and Haga, K and Takahashi, M and Arakawa, A and Shibuya, T and Osada, T and Kuwahara-Arai, K and Kirikae, T and Nagahara, A}, title = {Bacteroidetes Species Are Correlated with Disease Activity in Ulcerative Colitis.}, journal = {Journal of clinical medicine}, volume = {10}, number = {8}, pages = {}, pmid = {33920646}, issn = {2077-0383}, support = {JP16K09328//Japan Society for the Promotion of Science/ ; }, abstract = {Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger's clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with HSP60 as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (Alistipes putredinis, Bacteroides stercoris, Bacteroides uniformis, Bacteroides rodentium, and Parabacteroides merdae) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = -0.71, p = 2 × 10[-9]). Five genes (TARP, C10ORF54, ITGAE, TNFSF9, and LCN2) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.}, }
@article {pmid33918147, year = {2021}, author = {Augustus, E and Zwaenepoel, K and Siozopoulou, V and Raskin, J and Jordaens, S and Baggerman, G and Sorber, L and Roeyen, G and Peeters, M and Pauwels, P}, title = {Prognostic and Predictive Biomarkers in Non-Small Cell Lung Cancer Patients on Immunotherapy-The Role of Liquid Biopsy in Unraveling the Puzzle.}, journal = {Cancers}, volume = {13}, number = {7}, pages = {}, pmid = {33918147}, issn = {2072-6694}, support = {00000000116000000177//Kom op tegen Kanker/ ; }, abstract = {In the last decade, immunotherapy has been one of the most important advances in the non-small cell lung cancer (NSCLC) treatment landscape. Nevertheless, only a subset of NSCLC patients benefits from it. Currently, the only Food and Drug Administration (FDA) approved diagnostic test for first-line immunotherapy in metastatic NSCLC patients uses tissue biopsies to determine the programmed death ligand 1 (PD-L1) status. However, obtaining tumor tissue is not always feasible and puts the patient at risk. Liquid biopsy, which refers to the tumor-derived material present in body fluids, offers an alternative approach. This less invasive technique gives real-time information on the tumor characteristics. This review addresses different promising liquid biopsy based biomarkers in NSCLC patients that enable the selection of patients who benefit from immunotherapy and the monitoring of patients during this therapy. The challenges and the opportunities of blood-based biomarkers such as cell-free DNA (cfDNA), circulating tumor cells (CTCs), exosomes, epigenetic signatures, microRNAs (miRNAs) and the T cell repertoire will be addressed. This review also focuses on the less-studied feces-based and breath-based biomarkers.}, }
@article {pmid33915885, year = {2021}, author = {Canale, MP and Noce, A and Di Lauro, M and Marrone, G and Cantelmo, M and Cardillo, C and Federici, M and Di Daniele, N and Tesauro, M}, title = {Gut Dysbiosis and Western Diet in the Pathogenesis of Essential Arterial Hypertension: A Narrative Review.}, journal = {Nutrients}, volume = {13}, number = {4}, pages = {}, pmid = {33915885}, issn = {2072-6643}, mesh = {*Diet, Western ; Dysbiosis/*etiology ; *Gastrointestinal Microbiome ; Humans ; Hypertension/*etiology/physiopathology ; }, abstract = {Metabolic syndrome is a cluster of the most dangerous cardiovascular (CV) risk factors including visceral obesity, insulin resistance, hyperglycemia, alterations in lipid metabolism and arterial hypertension (AH). In particular, AH plays a key role in the complications associated with metabolic syndrome. High salt intake is a well-known risk factor for AH and CV diseases. Vasoconstriction, impaired vasodilation, extracellular volume expansion, inflammation, and an increased sympathetic nervous system (SNS) activity are the mechanisms involved in the pathogenesis of AH, induced by Western diet. Gut dysbiosis in AH is associated with reduction of short chain fatty acid-producing bacteria: acetate, butyrate and propionate, which activate different pathways, causing vasoconstriction, impaired vasodilation, salt and water retention and a consequent high blood pressure. Moreover, increased trimethylamine N-oxide and lipopolysaccharides trigger chronic inflammation, which contributes to endothelial dysfunction and target organs damage. Additionally, a high salt-intake diet impacts negatively on gut microbiota composition. A bidirectional neuronal pathway determines the "brain-gut" axis, which, in turn, influences blood pressure levels. Then, we discuss the possible adjuvant novel treatments related to gut microbiota modulation for AH control.}, }
@article {pmid33914709, year = {2021}, author = {Chaves, LD and Abyad, S and Honan, AM and Bryniarski, MA and McSkimming, DI and Stahura, CM and Wells, SC and Ruszaj, DM and Morris, ME and Quigg, RJ and Yacoub, R}, title = {Unconjugated p-cresol activates macrophage macropinocytosis leading to increased LDL uptake.}, journal = {JCI insight}, volume = {6}, number = {11}, pages = {}, pmid = {33914709}, issn = {2379-3708}, support = {UL1 TR001412/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Aorta/drug effects/*metabolism/pathology ; Cholesterol/metabolism ; Cholesterol, LDL/drug effects/*metabolism ; Coronary Artery Disease/*metabolism/pathology ; Coronary Vessels/drug effects/metabolism/pathology ; Cresols/*metabolism/pharmacology ; Diet, High-Fat ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Kidney Failure, Chronic/metabolism/microbiology ; Liver/drug effects/*metabolism/pathology ; Macrophages/drug effects/*metabolism ; Mice ; Pinocytosis/drug effects/*physiology ; Renal Insufficiency, Chronic/*metabolism/microbiology ; Triglycerides/metabolism ; }, abstract = {Patients with chronic kidney disease (CKD) and end-stage renal disease suffer from increased cardiovascular events and cardiac mortality. Prior studies have demonstrated that a portion of this enhanced risk can be attributed to the accumulation of microbiota-derived toxic metabolites, with most studies focusing on the sulfonated form of p-cresol (PCS). However, unconjugated p-cresol (uPC) itself was never assessed due to rapid and extensive first-pass metabolism that results in negligible serum concentrations of uPC. These reports thus failed to consider the host exposure to uPC prior to hepatic metabolism. In the current study, not only did we measure the effect of altering the intestinal microbiota on lipid accumulation in coronary arteries, but we also examined macrophage lipid uptake and handling pathways in response to uPC. We found that atherosclerosis-prone mice fed a high-fat diet exhibited significantly higher coronary artery lipid deposits upon receiving fecal material from CKD mice. Furthermore, treatment with uPC increased total cholesterol, triglycerides, and hepatic and aortic fatty deposits in non-CKD mice. Studies employing an in vitro macrophage model demonstrated that uPC exposure increased apoptosis whereas PCS did not. Additionally, uPC exhibited higher potency than PCS to stimulate LDL uptake and only uPC induced endocytosis- and pinocytosis-related genes. Pharmacological inhibition of varying cholesterol influx and efflux systems indicated that uPC increased macrophage LDL uptake by activating macropinocytosis. Overall, these findings indicate that uPC itself had a distinct effect on macrophage biology that might have contributed to increased cardiovascular risk in patients with CKD.}, }
@article {pmid33914693, year = {2021}, author = {Delapena, S and Spadafore, P and Bollenbach, SE and Kowal-Vern, A and Foster, KN and Matthews, MR}, title = {Rare Operative Intervention for Urinary and Fecal Incontinence-Associated Dermatitis.}, journal = {Wounds : a compendium of clinical research and practice}, volume = {33}, number = {4}, pages = {E31-E33}, pmid = {33914693}, issn = {1943-2704}, mesh = {Aged ; Aged, 80 and over ; *Dermatitis/etiology ; *Fecal Incontinence/complications ; Female ; Humans ; Male ; Skin ; Skin Care ; Skin Transplantation ; }, abstract = {Incontinence-associated dermatitis (IAD) is considered a cause of moisture-associated skin damage after prolonged exposure to urinary and fecal incontinence. While partial-thickness burns are often managed with topical therapies, daily dressing changes, patient positioning, hydration, nutrition, and pain management, deep partial-thickness and full-thickness burn injuries require surgical excision and, ultimately, skin grafting. The elderly and very young as well as those with medical comorbidities can develop urinary and fecal incontinence. Urinary ammonia and gastrointestinal lipolytic enzymes and proteases can produce caustic damage to weakened elderly or immature skin. In this report, 2 cases of IAD are presented as chemical burns. After a prolonged interval of urinary and fecal incontinence, an incapacitated 65-year-old male with 14% total body surface area (TBSA) partial-thickness wounds, and an 85-year-old female with 4% TBSA full-thickness wounds were admitted to the burn center and underwent operative management.}, }
@article {pmid33912150, year = {2021}, author = {Xu, HM and Huang, HL and Xu, J and He, J and Zhao, C and Peng, Y and Zhao, HL and Huang, WQ and Cao, CY and Zhou, YJ and Zhou, YL and Nie, YQ}, title = {Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {658292}, pmid = {33912150}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography-mass spectrometry (LC-MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.}, }
@article {pmid33912062, year = {2021}, author = {Schmidt, C and Grunert, PC and Stallmach, A}, title = {An Update for Pharmacologists on New Treatment Options for Inflammatory Bowel Disease: The Clinicians' Perspective.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {655054}, pmid = {33912062}, issn = {1663-9812}, abstract = {The introduction of anti-tumor necrosis factor antibodies resulted in a considerable expansion of the options available for the treatment of inflammatory bowel disease. Unfortunately, approximately one third of treated patients do not respond to these modalities, and drug efficacy may be lost over time. These drugs are also associated with contraindications, adverse events, and intolerance. As such, there is an ongoing need for new therapeutic strategies. Despite several recent advances, including antibodies against pro-inflammatory cytokines and cell adhesion molecules, Janus kinase inhibitors, and modulators of sphingosine-1-phosphate receptors, not all problems associated with IBD have been solved. In this manuscript, we review the current state of development of several new treatment options. Ongoing evaluation will require specific proof of efficacy as well as direct comparisons with established treatments. Results from head-to-head comparisons are needed to provide clinicians with critical information on how to formulate effective therapeutic approaches for each patient.}, }
@article {pmid33911125, year = {2021}, author = {Kato, S and Sato, T and Fujita, H and Kawatani, M and Yamada, Y}, title = {Effects of GLP-1 receptor agonist on changes in the gut bacterium and the underlying mechanisms.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {9167}, pmid = {33911125}, issn = {2045-2322}, mesh = {Adrenalectomy ; Animals ; Appetite ; Cecum/drug effects/metabolism ; Colitis/chemically induced/drug therapy/genetics/microbiology ; Endopeptidase Clp/metabolism ; Escherichia coli/drug effects ; Escherichia coli Proteins/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Glucagon-Like Peptide 1/metabolism ; Glucagon-Like Peptide-1 Receptor/metabolism ; Heat-Shock Proteins/metabolism ; Liraglutide/*pharmacology ; Mice, Inbred C57BL ; Norepinephrine/*metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Sympathetic Nervous System/drug effects/metabolism ; Mice ; *Glucagon-Like Peptide-1 Receptor Agonists ; }, abstract = {There is a close relationship between the gut microbiota and metabolic disorders. In this study, acute administration of the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide to mice increased the cecal levels of caseinolytic protease B, a component of Escherichia coli, and of norepinephrine. Chemical sympathectomy blocked these events. Norepinephrine was found to pass into the intestinal lumen in vitro. c-Fos staining of the intermediolateral nucleus was identified as indirect evidence of sympathetic nervous system activation of the intestinal tract by GLP-1RA. Under normal conditions, the increase in E. coli did not affect the host. However, in mice with colitis, bacterial translocation was observed with attenuation of tight junction gene expression. This is the first study to investigate the unique underlying mechanisms related the effects of GLP-1RA on changes in the gut bacterium.}, }
@article {pmid33910622, year = {2021}, author = {Su, F and Luo, Y and Yu, J and Shi, J and Zhao, Y and Yan, M and Huang, H and Tan, Y}, title = {Tandem fecal microbiota transplantation cycles in an allogeneic hematopoietic stem cell transplant recipient targeting carbapenem-resistant Enterobacteriaceae colonization: a case report and literature review.}, journal = {European journal of medical research}, volume = {26}, number = {1}, pages = {37}, pmid = {33910622}, issn = {2047-783X}, support = {81670169//National Natural Science Foundation of China/ ; 2010KYA075//the Medical Science and Technology Project of Zhejiang Province/ ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Carbapenem-Resistant Enterobacteriaceae/*isolation &amp; purification ; *Drug Resistance, Multiple, Bacterial ; Enterobacteriaceae Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Leukemia, Myeloid, Acute/microbiology/pathology/*therapy ; Male ; Middle Aged ; Transplantation, Homologous ; }, abstract = {BACKGROUND: Due to limited antibiotic options, carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Also, intestinal CRE colonization is a risk factor for subsequent CRE infection. Several clinical studies have reported successful fecal microbiota transplantation (FMT) for the gut decontamination of a variety of multidrug-resistant bacteria (MDRB), even in immunosuppressed patients. Similarly, other studies have also indicated that multiple FMTs may increase or lead to successful therapeutic outcomes.<br><br>CASE PRESENTATION: We report CRE colonization in an allo-HSCT patient with recurrent CRE infections, and its successful eradication using tandem FMT cycles at 488&#xa0;days after allo-HSCT. We also performed a comprehensive microbiota analysis. No acute or delayed adverse events (AEs) were observed. The patient remained clinically stable with CRE-negative stool culture at 26-month follow-up. Our analyses also showed some gut microbiota reconstruction. We also reviewed the current literature on decolonization strategies for CRE.<br><br>CONCLUSIONS: CRE colonization led to a high no-relapse mortality after allo-HSCT; however, well-established decolonization strategies are currently lacking. The successful decolonization of this patient suggests that multiple FMT cycles may be potential options for CRE decolonization.}, }
@article {pmid33907321, year = {2021}, author = {Danne, C and Rolhion, N and Sokol, H}, title = {Recipient factors in faecal microbiota transplantation: one stool does not fit all.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {18}, number = {7}, pages = {503-513}, pmid = {33907321}, issn = {1759-5053}, mesh = {Digestive System Diseases/genetics/*therapy ; Donor Selection ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/immunology/*physiology ; Humans ; *Inflammation/etiology/physiopathology/therapy ; Life Style ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) is a promising therapy for chronic diseases associated with gut microbiota alterations. FMT cures 90% of recurrent Clostridioides difficile infections. However, in complex diseases, such as inflammatory bowel disease, irritable bowel syndrome and metabolic syndrome, its efficacy remains variable. It is accepted that donor selection and sample administration are key determinants of FMT success, yet little is known about the recipient factors that affect it. In this Perspective, we discuss the effects of recipient parameters, such as genetics, immunity, microbiota and lifestyle, on donor microbiota engraftment and clinical efficacy. Emerging evidence supports the possibility that controlling inflammation in the recipient intestine might facilitate engraftment by reducing host immune system pressure on the newly transferred microbiota. Deciphering FMT engraftment rules and developing novel therapeutic strategies are priorities to alleviate the burden of chronic diseases associated with an altered gut microbiota such as inflammatory bowel disease.}, }
@article {pmid33897618, year = {2021}, author = {Huda, MN and Kim, M and Bennett, BJ}, title = {Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {632335}, pmid = {33897618}, issn = {1664-2392}, support = {R01 HL148110/HL/NHLBI NIH HHS/United States ; R01 HL128572/HL/NHLBI NIH HHS/United States ; }, mesh = {Diabetes Mellitus, Type 2/etiology/*therapy ; Dysbiosis/complications/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; *Prebiotics ; Probiotics/*therapeutic use ; }, abstract = {Mounting evidence suggested that the gut microbiota has a significant role in the metabolism and disease status of the host. In particular, Type 2 Diabetes (T2D), which has a complex etiology that includes obesity and chronic low-grade inflammation, is modulated by the gut microbiota and microbial metabolites. Current literature supports that unbalanced gut microbial composition (dysbiosis) is a risk factor for T2D. In this review, we critically summarize the recent findings regarding the role of gut microbiota in T2D. Beyond these associative studies, we focus on the causal relationship between microbiota and T2D established using fecal microbiota transplantation (FMT) or probiotic supplementation, and the potential underlying mechanisms such as byproducts of microbial metabolism. These microbial metabolites are small molecules that establish communication between microbiota and host cells. We critically summarize the associations between T2D and microbial metabolites such as short-chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Additionally, we comment on how host genetic architecture and the epigenome influence the microbial composition and thus how the gut microbiota may explain part of the missing heritability of T2D found by GWAS analysis. We also discuss future directions in this field and how approaches such as FMT, prebiotics, and probiotics supplementation are being considered as potential therapeutics for T2D.}, }
@article {pmid33896875, year = {2021}, author = {Sugita, K and Shima, A and Takahashi, K and Matsuda, Y and Miyajima, M and Hirokawa, M and Kondo, H and Kimura, J and Ishihara, G and Ohmori, K}, title = {Successful outcome after a single endoscopic fecal microbiota transplantation in a Shiba dog with non-responsive enteropathy during the treatment with chlorambucil.}, journal = {The Journal of veterinary medical science}, volume = {83}, number = {6}, pages = {984-989}, pmid = {33896875}, issn = {1347-7439}, mesh = {Animals ; Chlorambucil/therapeutic use ; Diarrhea/veterinary ; *Dog Diseases/drug therapy ; Dogs ; Dysbiosis/veterinary ; Fecal Microbiota Transplantation/veterinary ; Feces ; *Intestinal Diseases/veterinary ; Male ; Treatment Outcome ; }, abstract = {A 7-year 6-month-old, castrated male Shiba dog presented with a 1-month history of lethargy, anorexia, vomiting, and frequent watery diarrhea. Weight loss, hypoalbuminemia, anemia, and leukocytosis were detected at the first visit. The dog was diagnosed with non-responsive enteropathy (NRE) based on clinical and histopathological examinations. Since the dog did not respond to the immunosuppressive drugs, fecal microbiota transplantation (FMT) was performed during the treatment with chlorambucil. A single endoscopic FMT into the cecum and colon drastically recovered clinical signs and clinicopathological abnormalities and corrected dysbiosis in the dog. No recurrence or adverse events were observed. The present case report suggests that FMT, possibly together with chlorambucil, might be a treatment option for NRE in Shiba dogs that have poorer prognosis compared with other dog breeds.}, }
@article {pmid33896117, year = {2021}, author = {Lang, S and Martin, A and Zhang, X and Farowski, F and Wisplinghoff, H and J G T Vehreschild, M and Krawczyk, M and Nowag, A and Kretzschmar, A and Scholz, C and Kasper, P and Roderburg, C and Mohr, R and Lammert, F and Tacke, F and Schnabl, B and Goeser, T and Steffen, HM and Demir, M}, title = {Combined analysis of gut microbiota, diet and PNPLA3 polymorphism in biopsy-proven non-alcoholic fatty liver disease.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {41}, number = {7}, pages = {1576-1591}, pmid = {33896117}, issn = {1478-3231}, support = {P30 DK120515/DK/NIDDK NIH HHS/United States ; }, mesh = {Aged ; Biopsy ; Cross-Sectional Studies ; Diet ; *Gastrointestinal Microbiome ; Humans ; Lipase/genetics ; Liver ; Membrane Proteins/genetics ; *Non-alcoholic Fatty Liver Disease/genetics ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a global health burden. Risk factors for disease severity include older age, increased body mass index (BMI), diabetes, genetic variants, dietary factors and gut microbiota alterations. However, the interdependence of these factors and their individual impact on disease severity remain unknown.<br><br>METHODS: In this cross-sectional study, we performed 16S gene sequencing using fecal samples, collected dietary intake, PNPLA3 gene variants and clinical and liver histology parameters in a well-described cohort of 180 NAFLD patients. Principal component analyses were used for dimensionality reduction of dietary and microbiota data. Simple and multiple stepwise ordinal regression analyses were performed.<br><br>RESULTS: Complete data were available for 57 NAFLD patients. In the simple regression analysis, features associated with the metabolic syndrome had the highest importance regarding liver disease severity. In the multiple regression analysis, BMI was the most important factor associated with the fibrosis stage (OR per kg/m[2] : 1.23, 95% CI 1.10-1.37, P&#xa0;<&#xa0;.001). The PNPLA3 risk allele had the strongest association with the histological grade of steatosis (OR 5.32, 95% CI 1.56-18.11, P&#xa0;=&#xa0;.007), followed by specific dietary patterns. Low abundances of Faecalibacterium, Bacteroides and Prevotella and high abundances of Gemmiger were associated with the degree of inflammation, ballooning and stages of fibrosis, even after taking other cofactors into account.<br><br>CONCLUSIONS: BMI had the strongest association with histological fibrosis, but PNPLA3 gene variants, gut bacterial features and dietary factors were all associated with different histology features, which underscore the multifactorial pathogenesis of NAFLD.}, }
@article {pmid33894059, year = {2021}, author = {Sun, J and Chen, YL and Ding, YC and Zhong, H and Wu, M and Liu, ZH and Ge, LP}, title = {Deposition of resistant bacteria and resistome through FMT in germ-free piglets.}, journal = {Letters in applied microbiology}, volume = {73}, number = {2}, pages = {187-196}, doi = {10.1111/lam.13490}, pmid = {33894059}, issn = {1472-765X}, support = {cstc2019jxjl80019//Chongqing Scientific Research Institute Performance Incentive and Guidance Special Project/ ; 21509(20227)//Chongqing Basic Scientific Research/ ; 20206//the Key R &amp; D Project in Agriculture and Animal Husbandries of Rongchang/ ; }, mesh = {Age Factors ; Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/*classification/*drug effects ; Biodiversity ; DNA, Bacterial ; Drug Resistance, Multiple, Bacterial/*genetics ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; Interspersed Repetitive Sequences ; Metagenomics ; Swine ; Virulence Factors/*genetics ; }, abstract = {Faecal microbiota transplantation (FMT) has received considerable attention in recent years due to its remarkable efficacy in restoring a normal gut microbiome. Here, we established the groups of post-FMT recipient piglets using germ-free piglets during early life to characterize the colonization of gut microbiota composition and the enrichment of resistance gene acquisition. By metagenomic analysis, we identified 115 bacterial phyla and 2111 bacterial genera that were acquired by the FMT recipients. We found that early-life microbial colonization and the spread of resistomes in recipient piglets were age dependent. A total of 425, 425 and 358 AR genes primarily belonging to 114, 114 and 102 different types were detected in the donors, post-FMT recipients in the FMT-3D group and post-FMT recipients in the FMT-15D group respectively. Genes that encoded tetracycline, macrolide and chloramphenicol resistance proteins were the most dominant AR genes, and the results corresponded with the exposure of antibiotic consumption at farm. Bacteroides, Escherichia, Clostridium, Parabacteroides, Treponema, Lactobacillus and Enterococcus were significantly correlated with the distribution of AR genes. More importantly, the relative abundance of AR genes was positively correlated with the levels of mobile genetic elements. Our results indicate that early-life microbial colonization can persistently shape the gut microbiota and antibiotic resistome.}, }
@article {pmid33889942, year = {2021}, author = {Concannon, E and Coghlan, P and DamKat Thomas, L and Solanki, NS and Greenwood, JE}, title = {Biodegradable Temporizing Matrix Reconstruction of Complex Perineal Burn Wound: A Case Report.}, journal = {Journal of burn care &amp; research : official publication of the American Burn Association}, volume = {42}, number = {5}, pages = {1038-1042}, doi = {10.1093/jbcr/irab073}, pmid = {33889942}, issn = {1559-0488}, mesh = {Aged ; Burns/*surgery ; Graft Survival ; Humans ; Male ; Perineum/*injuries ; Skin Transplantation/*methods ; Soft Tissue Injuries/surgery ; Wound Healing/*physiology ; }, abstract = {This case report details our experience using a two-stage Biodegradable Temporizing Matrix (NovoSorb® PolyNovo Ltd) and autograft for acute reconstruction of a complex perineal burn wound in an elderly comorbid patient. A 77-year-old man sustained 42% full-thickness burns extending circumferentially from bilateral thighs and buttocks, across the entire perineal and genital regions up to his mid-trunk, following self-immolation using an accelerant. Early total burn wound excision was carried out with acute application of Biodegradable Temporizing Matrix to all affected sites. Excellent integration and vascularization of Biodegradable Temporizing Matrix took place despite the challenge of intermittent fecal contamination affecting the perineal and buttock burn sites and matrix colonization with multidrug-resistant organisms. Delamination and serial split-thickness skin autografting were carried out 42 days after the first matrix application with complete and robust graft take. Perineal burns present a reconstructive challenge due to the proximity of specialized structures such as the genitalia, urethral, and anal orifices. Restoration of complex anatomy and function may be required after debridement with increased risks of infection, contracture formation, and mortality compared with burns affecting other anatomical sites. Two-stage Biodegradable Temporizing Matrix represents a reliable reconstruction option for complex extensive perineal wounds in frail elderly patients, despite an unfavorable local microbial environment.}, }
@article {pmid33888680, year = {2021}, author = {Kong, C and Yan, X and Liu, Y and Huang, L and Zhu, Y and He, J and Gao, R and Kalady, MF and Goel, A and Qin, H and Ma, Y}, title = {Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome.}, journal = {Signal transduction and targeted therapy}, volume = {6}, number = {1}, pages = {154}, pmid = {33888680}, issn = {2059-3635}, mesh = {Animals ; Bacteria/classification/immunology ; *Colitis/immunology/microbiology ; Cytokines/immunology ; *Diet, Ketogenic ; Gastrointestinal Microbiome/*immunology ; *Immunity, Innate ; Lymphocytes/*immunology ; Male ; Mice ; }, abstract = {Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, the consequences of this unique diet on colitis remain unknown. We performed a series of systematic studies using a dextran sulfate sodium (DSS) animal model of inflammatory colitis. Animals were fed with a KD, low-carbohydrate diet (LCD), or normal diet (ND). Germ-free mice were utilized in validation experiments. Colon tissues were analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, and immunofluorescence. Serum samples were analyzed by metabolic assay kit. Fecal samples were analyzed by 16S rRNA gene sequencing, liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD. Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia, whereas the opposite was observed for Escherichia/Shigella. After colitis induction, the KD protected intestinal barrier function, and reduced the production of RORγt[+]CD3[-] group 3 innate lymphoid cells (ILC3s) and related inflammatory cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal microbiota transplantation into germ-free mice revealed that the KD- mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota. Taken together, our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment, and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.}, }
@article {pmid33887125, year = {2021}, author = {Bayoumy, AB and Mulder, CJJ and Mol, JJ and Tushuizen, ME}, title = {Gut fermentation syndrome: A systematic review of case reports.}, journal = {United European gastroenterology journal}, volume = {9}, number = {3}, pages = {332-342}, pmid = {33887125}, issn = {2050-6414}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antifungal Agents/therapeutic use ; Bias ; Candida/metabolism ; Diet, Carbohydrate-Restricted ; Dietary Carbohydrates/*metabolism ; Ethanol/*metabolism ; Fecal Microbiota Transplantation ; *Fermentation ; Gastrointestinal Microbiome/*physiology ; Humans ; Klebsiella pneumoniae/metabolism ; Medical Records/statistics &amp; numerical data ; Non-alcoholic Fatty Liver Disease/microbiology ; Probiotics/therapeutic use ; Saccharomyces cerevisiae/metabolism ; Syndrome ; }, abstract = {BACKGROUND: The gut fermentation syndrome (GFS), also known as the endogenous alcohol fermentation syndrome or auto brewery syndrome, is a rare and underdiagnosed medical condition where consumed carbohydrates are converted to alcohol by the microbiota in the gastrointestinal or urinary tract. The symptoms of GFS can have severe impact on patients' wellbeing and can have social and legal consequences. Unfortunately, not much is reported about GFS. The aim of this systematic review was to assess the evidence for GFS, causal micro-organisms, diagnostics, and possible treatments.<br><br>METHODS: A protocol was developed prior to initiation of the systematic review (PROSPERO 207182). We performed a literature search for clinical studies on 1 September 2020 using PubMed and Embase. We included all clinical studies, including case reports that described the GFS.<br><br>RESULTS: In total, 17 case reports were included, consisting of 20 patients diagnosed with GFS. The species that caused the GFS included Klebsiella pneumoniae, Candida albicans, C. glabrata, Saccharomyces cerevisiae, C. intermedia, C. parapsilosis, and C. kefyr.<br><br>CONCLUSIONS: GFS is a rare but underdiagnosed disease in daily practice. The disease is mostly reported by Saccharomyces and Candida genera, and some cases were previously treated with antibiotics. Studies in Nonalcoholic Fatty Liver disease suggest a bacterial origin of endogenous alcohol-production, which might also be causal micro-organisms in GFS. Current treatments for GFS include antibiotics, antifungal medication, low carbohydrate diet, and probiotics. There might be a potential role of fecal microbiota transplant in the treatment of GFS.}, }
@article {pmid33883600, year = {2021}, author = {Öhman, L and Lasson, A and Strömbeck, A and Isaksson, S and Hesselmar, M and Simrén, M and Strid, H and Magnusson, MK}, title = {Fecal microbiota dynamics during disease activity and remission in newly diagnosed and established ulcerative colitis.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {8641}, pmid = {33883600}, issn = {2045-2322}, mesh = {Adult ; Colitis, Ulcerative/*microbiology ; Disease Progression ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/methods ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Male ; Microbiota/physiology ; Middle Aged ; Recurrence ; Remission Induction/methods ; Young Adult ; }, abstract = {Patients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2-6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3-10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.}, }
@article {pmid33883174, year = {2021}, author = {de Clercq, NC and van den Ende, T and Prodan, A and Hemke, R and Davids, M and Pedersen, HK and Nielsen, HB and Groen, AK and de Vos, WM and van Laarhoven, HWM and Nieuwdorp, M}, title = {Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer: A Randomized, Double-blind, Placebo-Controlled, Phase II Study.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {27}, number = {13}, pages = {3784-3792}, doi = {10.1158/1078-0432.CCR-20-4918}, pmid = {33883174}, issn = {1557-3265}, mesh = {Adult ; Aged ; Cachexia/*etiology/microbiology/*therapy ; Double-Blind Method ; Esophageal Neoplasms/*complications/microbiology/pathology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Obesity/microbiology ; Overweight/microbiology ; Stomach Neoplasms/*complications/microbiology/pathology ; }, abstract = {PURPOSE: Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer.<br><br>EXPERIMENTAL DESIGN: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics).<br><br>RESULTS: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n = 12) had a higher DCR at 12 weeks (P = 0.035) compared with the autologous group (n = 12), longer median OS of 365 versus 227 days [HR = 0.38; 95% confidence interval (CI), 0.14-1.05; P = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21-1.20; P = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (P = 0.010) indicating proper engraftment of the donor microbiota.<br><br>CONCLUSIONS: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.}, }
@article {pmid33883079, year = {2021}, author = {Rinott, E and Youngster, I and Meir, AY and Tsaban, G and Kaplan, A and Zelicha, H and Rubin, E and Koren, O and Shai, I}, title = {Autologous fecal microbiota transplantation can retain the metabolic achievements of dietary interventions.}, journal = {European journal of internal medicine}, volume = {92}, number = {}, pages = {17-23}, doi = {10.1016/j.ejim.2021.03.038}, pmid = {33883079}, issn = {1879-0828}, mesh = {*Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Middle Aged ; Obesity/therapy ; Weight Loss ; }, abstract = {BACKGROUND: We recently reported that autologous fecal microbiota transplantation (aFMT), derived from the time of maximal weight-loss and administrated in the regain-phase, might preserve weight loss and glycemic control in moderately obese subjects, and is associated with specific microbiome signatures. Here, we sought to explore the global effect of aFMT on adipokines, inflammatory markers and blood cholesterol and on the overall gut microbiome preservation.<br><br>METHODS: In the DIRECT-PLUS weight-loss trial, abdominally obese participants were randomized to three distinct weight-loss diets. Following the expected weight loss phase (0-6&#xa0;m), 90 participants were randomized to receive their personal frozen fecal microbiota or placebo oral capsules (ten 1 g-capsules over ten sessions-total=100&#xa0;g) during the expected weight regain phase (8-14&#xa0;m).<br><br>RESULTS: Of the 90 participants (age=52&#xa0;yr; 0-6&#xa0;m weight loss=-8.3&#xa0;kg), 95.6% ingested at least 80/100 oral aFMT/placebo capsules over 6 months. Overall, the gut microbiome community structure was associated with plasma levels of leptin, cholesterol and interleukin-6 at baseline and after 6&#xa0;m, whereas 6&#xa0;m (weight loss phase) changes in specific microbiome species associated with the dynamic of leptin and inflammatory biomarkers. Following the 8-14&#xa0;m aFMT administration phase, aFMT maintained decreased levels of leptin (&#x394;aFMT=-3.54&#xa0;ng/mL vs. &#x394;placebo=-0.82&#xa0;ng/mL;P&#xa0;=&#xa0;0.04), C-reactive-protein (&#x394;aFMT=-1.45&#xa0;mg/L vs. &#x394;placebo=-0.66&#xa0;mg/L;P&#xa0;=&#xa0;0.009), Interleukin-6 (&#x394;aFMT=-0.03pg/mL vs. &#x394;placebo=1.11pg/mL;P&#xa0;=&#xa0;0.03) and total cholesterol (&#x394;aFMT=2.2&#xa0;mg/dl vs. &#x394;placebo=13.1&#xa0;mg/dl;P&#xa0;=&#xa0;0.04) achieved in the weight loss phase. Overall, aFMT induced a significant preservatory effect on personal gut microbiome global composition (P&#xa0;=&#xa0;0.03;Jensen-Shannon distance), as compared to placebo.<br><br>CONCLUSIONS: aFMT treatment in the regain phase might retain weight-loss induced metabolic benefits. These findings may suggest a novel aFMT treatment approach for personal metabolic attainment preservation.}, }
@article {pmid33882637, year = {2021}, author = {Van Lier, YF and Van den Brink, MRM and Hazenberg, MD and Markey, KA}, title = {The post-hematopoietic cell transplantation microbiome: relationships with transplant outcome and potential therapeutic targets.}, journal = {Haematologica}, volume = {106}, number = {8}, pages = {2042-2053}, pmid = {33882637}, issn = {1592-8721}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {*Graft vs Host Disease/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; *Microbiota ; Transplantation Conditioning/adverse effects ; Transplantation, Homologous ; }, abstract = {Microbiota injury occurs in many patients undergoing allogeneic hematopoietic cell transplantation, likely as a consequence of conditioning regimens involving chemo- and radiotherapy, the widespread use of both prophylactic and therapeutic antibiotics, and profound dietary changes during the peri-transplant period. Peri-transplant dysbiosis is characterized by a decrease in bacterial diversity, loss of commensal bacteria and single-taxon domination (e.g., with Enterococcal strains). Clinically, deviation of the post-transplant microbiota from a normal, high-diversity, healthy state has been associated with increased risk of bacteremia, development of graft-versus-host disease and decreases in overall survival. A number of recent clinical trials have attempted to target the microbiota in allogeneic hematopoietic cell transplantation patients via dietary interventions, selection of therapeutic antibiotics, administration of pre- or pro-biotics, or by performing fecal microbiota transplantation. These strategies have yielded promising results but the mechanisms by which these interventions influence transplant-related complications remain largely unknown. In this review we summarize the current approaches to targeting the microbiota, discuss potential underlying mechanisms and highlight the key outstanding areas that require further investigation in order to advance microbiota- targeting therapies.}, }
@article {pmid33881598, year = {2022}, author = {Metta, V and Leta, V and Mrudula, KR and Prashanth, LK and Goyal, V and Borgohain, R and Chung-Faye, G and Chaudhuri, KR}, title = {Gastrointestinal dysfunction in Parkinson's disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation.}, journal = {Journal of neurology}, volume = {269}, number = {3}, pages = {1154-1163}, pmid = {33881598}, issn = {1432-1459}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; *Parkinson Disease/complications/pathology/therapy ; Pathology, Molecular ; *Probiotics/therapeutic use ; }, abstract = {Gastrointestinal symptoms and gut dysbiosis may occur before the onset of motor symptoms in Parkinson's disease (PD). Prediagnostic and prodromal features, such as constipation and α-synuclein pathology, can be detected several years before the clinical diagnosis of PD and have the potential to develop as early PD biomarkers. Environmental toxins and gut dysbiosis may trigger oxidative stress and mucosal inflammation, and initiate α-synuclein accumulation in the enteric nervous system, early in PD. Chronic gut inflammation can lead to a leaky gut and systemic inflammation, neuro inflammation, and neuro degeneration via gut-vagus-brain signaling or through blood-brain barrier permeability. Concepts regarding the gut-brain signaling in PD pathogenesis are changing rapidly and more investigation is required. The gut microbiota interacts with the human body by modulating the enteric and central nervous systems, and immune activity. Understanding the immune responses between gut microbiota and human body might help in elucidating the PD pathogenesis. As changes in gut microbiota composition might be associated with different clinical phenotypes of PD, gut microbiota-modulating interventions, such as probiotics and fecal microbiota transplantation (FMT), have the potential to restore the gut dysbiosis, reduce inflammation, and possibly modulate the clinical PD phenotype.}, }
@article {pmid33880565, year = {2021}, author = {Golob, JL and Rao, K}, title = {Signal Versus Noise: How to Analyze the Microbiome and Make Progress on Antimicrobial Resistance.}, journal = {The Journal of infectious diseases}, volume = {223}, number = {12 Suppl 2}, pages = {S214-S221}, pmid = {33880565}, issn = {1537-6613}, support = {R01 HS027431/HS/AHRQ HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/adverse effects ; Clostridioides difficile/growth &amp; development/pathogenicity ; Clostridium Infections/etiology/microbiology ; Disease Models, Animal ; Drug Resistance, Microbial/drug effects/*genetics ; Gastrointestinal Microbiome/drug effects/*genetics/immunology ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions ; Humans ; }, abstract = {Antimicrobial resistance has become a worldwide medical challenge [1], so impactful that vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) have entered the common vernacular. We have attempted to reduce the selective pressure through antimicrobial stewardship, curtail the spread by identifying and isolating carriers and individuals with symptomatic infection, and treat antibiotic-resistant organisms (AROs) by developing novel antimicrobials. Despite these extraordinary measures, the challenge of AROs continues to grow. The gut microbiome, the ecosystem of microbes (ie, the microbiota) and metabolites present upon and within all humans, is an emerging target for both the risk for colonization and defense against infection with AROs. Here, informed from experiences and successes with understanding the role of the microbiome in mediating risk of Clostridioides difficile infection (CDI), we (1) review our understanding of the risk from ARO acquisition; (2) review our current understanding of the gut microbiome's ability to resist colonization with AROs; (3) describe how experimental model systems can test these initial, global insights to arrive at more granular, mechanistic ones; and (4) suggest a path forward to make further progress in the field.}, }
@article {pmid33880485, year = {2021}, author = {Natarajan, A and Han, A and Zlitni, S and Brooks, EF and Vance, SE and Wolfe, M and Singh, U and Jagannathan, P and Pinsky, BA and Boehm, A and Bhatt, AS}, title = {Standardized and optimized preservation, extraction and quantification techniques for detection of fecal SARS-CoV-2 RNA.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {33880485}, support = {R01 AI143757/AI/NIAID NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; }, abstract = {COVID-19 patients shed SARS-CoV-2 viral RNA in their stool, sometimes well after they have cleared their respiratory infection. This feature of the disease may be significant for patient health, epidemiology, and diagnosis. However, to date, methods to preserve stool samples from COVID patients, and to extract and quantify viral RNA concentration have yet to be optimized. We sought to meet this urgent need by developing and benchmarking a standardized protocol for the fecal detection of SARS-CoV-2 RNA. We test three preservative conditions for their ability to yield detectable SARS-CoV-2 RNA: OMNIgene-GUT, Zymo DNA/RNA shield kit, and the most common condition, storage without any preservative. We test these in combination with three extraction kits: the QIAamp Viral RNA Mini Kit, Zymo Quick-RNA Viral Kit, and MagMAX Viral/Pathogen Kit. Finally, we also test the utility of two detection methods, ddPCR and RT-qPCR, for the robust quantification of SARS-CoV-2 viral RNA from stool. We identify that the Zymo DNA/RNA shield collection kit and the QiaAMP viral RNA mini kit yield more detectable RNA than the others, using both ddPCR and RT-qPCR assays. We also demonstrate key features of experimental design including the incorporation of appropriate controls and data analysis, and apply these techniques to effectively extract viral RNA from fecal samples acquired from COVID-19 outpatients enrolled in a clinical trial. Finally, we recommend a comprehensive methodology for future preservation, extraction and detection of RNA from SARS-CoV-2 and other coronaviruses in stool.}, }
@article {pmid33879696, year = {2021}, author = {Wang, N and Yao, W and Ma, R and Ren, F}, title = {The efficacy of a multistrain probiotic on cognitive function and risk of falls in patients with cirrhosis: A protocol for systematic review and meta-analysis.}, journal = {Medicine}, volume = {100}, number = {16}, pages = {e25535}, pmid = {33879696}, issn = {1536-5964}, support = {2015GSF121033//Shandong province key research and development project/ ; }, mesh = {Accidental Falls/*prevention &amp; control ; Cognition ; Cognitive Dysfunction/microbiology/*prevention &amp; control ; Female ; Humans ; Liver Cirrhosis/microbiology/*psychology/*therapy ; Male ; Meta-Analysis as Topic ; Probiotics/*therapeutic use ; Randomized Controlled Trials as Topic ; Research Design ; Risk Factors ; Systematic Reviews as Topic ; Treatment Outcome ; }, abstract = {OBJECTIVE: The effect of probiotics on cognitive function and the risk of falling in cirrhosis patients have not been previously evaluated. We perform this protocol for systematic review and meta-analysis to evaluate the effect of a multistrain probiotic on cognitive function and the risk of falls in patients with cirrhosis.<br><br>METHODS: An all-round retrieval will be performed in 5 electronic journal databases from their inception to March 2021, which comprise Medline, Pubmed, Embase, ScienceDirect, and the Cochrane Library by 2 independent reviewers. Data extraction was performed independently, and any conflict was resolved before final analysis. Only randomized clinical trials were included in this study. The main endpoints were cognitive function and risk of falls, and the secondary endpoints were fall incidence, health-related quality of life (HRQOL), systemic inflammatory response, gut barrier, bacterial translocation, and fecal microbiota. The risk of bias assessment of the included studies was performed by 2 authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions.<br><br>RESULTS: We hypothesized that the multistrain probiotic improved cognitive function, risk of falls, and inflammatory response in patients with cirrhosis and cognitive dysfunction.<br><br>CONCLUSION: This study expects to provide credible and scientific clinical evidence for the efficacy and safety of a multistrain probiotic on cognitive function and the risk of falls in patients with cirrhosis.<br><br>OSF REGISTRATION NUMBER: 10.17605/OSF.IO/JKMTP.}, }
@article {pmid33878733, year = {2021}, author = {Zhang, J and Chen, Z and Yu, H and Lu, Y and Yu, W and Miao, M and Shi, H}, title = {Anti-aging effects of a functional food via the action of gut microbiota and metabolites in aging mice.}, journal = {Aging}, volume = {13}, number = {13}, pages = {17880-17900}, pmid = {33878733}, issn = {1945-4589}, mesh = {Aging/genetics/*physiology ; Animals ; Antioxidants/metabolism ; Body Weight ; CA1 Region, Hippocampal/growth &amp; development/metabolism ; Diet ; Eating ; Feces/microbiology ; *Functional Food ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*metabolism/*microbiology ; Lymphocyte Count ; Male ; Mice ; Mice, Inbred Strains ; Nervous System Physiological Phenomena ; }, abstract = {Wushen (WS) is a mixed food containing 55 natural products that is beneficial to human health. This study aimed to reveal the preventive effect of WS on aging via a combined analysis of gut microbiome and metabolome. Senescence-accelerated mouse prone 8 (SAMP8) mice were used as aging model and senescence-accelerated mouse resistant 1 (SAMR1) mice as control. The mice were fed four diet types; control diet (for SAMR1 mice), standard diet (for SAMP8 mice, as SD group), WS diet, and fecal microbiota transplantation (FMT; transplanted from aging-WS mice). Our results showed that the weight, food intake, neurological function, and general physical conditions significantly improved in WS-fed mice compared to those fed with SD. The CA1 hippocampal region in WS-fed aged mice showed fewer shriveled neurons and increased neuronal layers compared to that of the SD group. WS-fed mice showed a decrease in malondialdehyde and an increase in superoxide dismutase levels in the brain; additionally, IL-6 and TNF-α levels significantly decreased, whereas IL-2 levels and the proportion of lymphocytes, CD3+CD8+ T, and CD4+IFNγ+T cells increased in WS-fed mice. After fed with WS, the abundance of Ruminococcus and Butyrivibrio markedly increased, whereas Lachnoclostridium and Ruminiclostridium significantly decreased in the aging mice. In addition, 887 differentially expressed metabolites were identified in fecal samples, among these, Butyrivibrio was positively correlated with D-glucuronic acid and Ruminococcus was positively associated with 5-acetamidovalerate. These findings provide mechanistic insight into the impact of WS on aging, and WS may be a valuable diet for preventing aging.}, }
@article {pmid33872339, year = {2021}, author = {Gal, A and Barko, PC and Biggs, PJ and Gedye, KR and Midwinter, AC and Williams, DA and Burchell, RK and Pazzi, P}, title = {One dog's waste is another dog's wealth: A pilot study of fecal microbiota transplantation in dogs with acute hemorrhagic diarrhea syndrome.}, journal = {PloS one}, volume = {16}, number = {4}, pages = {e0250344}, pmid = {33872339}, issn = {1932-6203}, mesh = {Actinobacteria/genetics/growth &amp; development/isolation &amp; purification ; Animals ; Bacteroidetes/genetics/growth &amp; development/isolation &amp; purification ; Clostridioides/genetics/growth &amp; development/*pathogenicity ; Clostridium Infections/microbiology/pathology/*therapy/veterinary ; Diarrhea/microbiology/pathology/*therapy/veterinary ; Dogs ; Fatty Acids, Volatile/biosynthesis ; Fecal Microbiota Transplantation/*veterinary ; Feces/*microbiology ; Female ; Firmicutes/genetics/growth &amp; development/isolation &amp; purification ; Fusobacteria/genetics/growth &amp; development/isolation &amp; purification ; Gastrointestinal Hemorrhage/microbiology/pathology/*therapy/veterinary ; Gastrointestinal Microbiome/*physiology ; Intestinal Mucosa/microbiology ; Male ; New Zealand ; Pilot Projects ; Prospective Studies ; Proteobacteria/genetics/growth &amp; development/isolation &amp; purification ; RNA, Ribosomal, 16S/genetics ; South Africa ; }, abstract = {Canine acute hemorrhagic diarrhea syndrome (AHDS) has been associated in some studies with Clostridioides perfringens overgrowth and toxin-mediated necrosis of the intestinal mucosa. We aimed to determine the effect of a single fecal microbiota transplantation (FMT) on clinical scores and fecal microbiomes of 1 and 7 dogs with AHDS from New Zealand and South Africa. We hypothesized that FMT would improve AHDS clinical scores and increase microbiota alpha-diversity and short-chain fatty acid (SCFA)-producing microbial communities' abundances in dogs with AHDS after FMT. We sequenced the V3-V4 region of the 16S-rRNA gene in the feces of AHDS FMT-recipients and sham-treated control dogs, and their healthy donors at admission, discharge, and 30 days post-discharge. There were no significant differences in median AHDS clinical scores between FMT-recipients and sham-treated controls at admission or discharge (P = 0.22, P = 0.41). At admission, the Shannon diversity index (SDI) was lower in AHDS dogs than healthy donors (P = 0.002). The SDI did not change from admission to 30 days in sham-treated dogs yet increased in FMT-recipients from admission to discharge (P = 0.04) to levels not different than donors (P = 0.33) but significantly higher than sham-treated controls (P = 0.002). At 30 days, the SDI did not differ between FMT recipients, sham-treated controls, and donors (P = 0.88). Principal coordinate analysis of the Bray-Curtis index separated post-FMT and donor dogs from pre-FMT and sham-treated dogs (P = 0.009) because of increased SCFA-producing genera's abundances after FMT. A single co-abundance subnetwork contained many of the same OTUs found to be differentially abundant in FMT-recipients, and the abundance of this module was increased in FMT-recipients at discharge and 30 days, compared to sham-treated controls. We conclude in this small pilot study FMT did not have any clinical benefit. A single FMT procedure has the potential to increase bacterial communities of SCFA-producing genera important for intestinal health up to 30 days post-FMT.}, }
@article {pmid33870869, year = {2021}, author = {Wuethrich, I and W Pelzer, B and Khodamoradi, Y and Vehreschild, MJGT}, title = {The role of the human gut microbiota in colonization and infection with multidrug-resistant bacteria.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-13}, pmid = {33870869}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Bacterial Infections/*immunology/*microbiology/*therapy/virology ; Bacteriophages ; Biological Therapy ; *Drug Resistance, Multiple, Bacterial ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Host Microbial Interactions ; Humans ; *Immunity ; Prebiotics ; Probiotics ; Vaccines ; }, abstract = {About 100 years ago, the first antibiotic drug was introduced into health care. Since then, antibiotics have made an outstanding impact on human medicine. However, our society increasingly suffers from collateral damage exerted by these highly effective drugs. The rise of resistant pathogen strains, combined with a reduction of microbiota diversity upon antibiotic treatment, has become a significant obstacle in the fight against invasive infections worldwide.Alternative and complementary strategies to classical "Fleming antibiotics" comprise microbiota-based treatments such as fecal microbiota transfer and administration of probiotics, live-biotherapeutics, prebiotics, and postbiotics. Other promising interventions, whose efficacy may also be influenced by the human microbiota, are phages and vaccines. They will facilitate antimicrobial stewardship, to date the only globally applied antibiotic resistance mitigation strategy.In this review, we present the available evidence on these nontraditional interventions, highlight their interaction with the human microbiota, and discuss their clinical applicability.}, }
@article {pmid33869077, year = {2021}, author = {Gao, Y and Zhang, J and Xiao, X and Ren, Y and Yan, X and Yue, J and Wang, T and Wu, Z and Lv, Y and Wu, R}, title = {The Role of Gut Microbiota in Duodenal-Jejunal Bypass Surgery-Induced Improvement of Hepatic Steatosis in HFD-Fed Rats.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {640448}, pmid = {33869077}, issn = {2235-2988}, mesh = {Animals ; *Diet, High-Fat ; Duodenum ; *Gastrointestinal Microbiome ; Jejunum ; Male ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Bariatric surgery including duodenal-jejunal bypass surgery (DJB) improves insulin sensitivity and reduces obesity-associated inflammation. However, the underlying mechanism for such an improvement is still incompletely understood. Our objective was to investigate the role of the gut microbiota in DJB-associated improvement of hepatic steatosis in high fat diet (HFD)-fed rats. To study this, hepatic steatosis was induced in male adult Sprague-Dawley rats by feeding them with a 60% HFD. At 8 weeks after HFD feeding, the rats were subjected to either DJB or sham operation. HFD was resumed 1 week after the surgery for 3 more weeks. In additional groups of animals, feces were collected from HFD-DJB rats at 2 weeks after DJB. These feces were then transplanted to HFD-fed rats without DJB at 8 weeks after HFD feeding. Hepatic steatosis and fecal microbiota were analyzed at 4 weeks after surgery or fecal transplantation. Our results showed that DJB alleviated hepatic steatosis in HFD-fed rats. Fecal microbiota analysis showed that HFD-fed and standard diet-fed rats clustered differently. DJB induced substantial compositional changes in the gut microbiota. The fecal microbiota of HFD-fed rats received fecal transplant from DJB rats overlapped with that of HFD-DJB rats. Treatment of rats with HFD-induced liver lesions by fecal transplant from DJB-operated HFD-fed rats also attenuated hepatic steatosis. Thus, alterations in the gut microbiota after DJB surgery are sufficient to attenuate hepatic steatosis in HFD-fed rats. Targeting the gut microbiota could be a promising approach for preventing or treating human NAFLD.}, }
@article {pmid33864273, year = {2021}, author = {Pomares Bascuñana, R&#xc1; and Veses, V and Sheth, CC}, title = {Effectiveness of fecal microbiota transplant for the treatment of Clostridioides difficile diarrhea: a systematic review and meta-analysis.}, journal = {Letters in applied microbiology}, volume = {73}, number = {2}, pages = {149-158}, doi = {10.1111/lam.13486}, pmid = {33864273}, issn = {1472-765X}, mesh = {Administration, Oral ; Capsules/administration &amp; dosage ; Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Diarrhea/microbiology/*therapy ; Enema ; Fecal Microbiota Transplantation/adverse effects/*methods ; Gastrointestinal Microbiome ; Humans ; Treatment Outcome ; }, abstract = {Clostridioides difficile is a major cause of health-care related infections and antibiotic-associated diarrhea. High recurrence rates following antibiotic treatment, along with the emergence of hypervirulent and multidrug resistant ribotypes makes essential the development of safe, effective, novel therapies for the treatment of C. difficile infections. The primary outcome evaluated in this meta-analysis was the effectiveness of fecal microbiota transplantation (FMT). Secondary outcomes were the proportion of patients suffering adverse effects along with the most effective administration route. The mean treatment effectiveness was 82% (95% CI: 75-89). Overall, patients receiving FMT via colonoscopy experienced more adverse effects than patients whom received enema, or oral capsules (71·6% vs 40·2%, and 35·3% respectively). Comparing administration of FMT by colonoscopy versus enema resulted in a Hedges' g of -0·74 (95% CI of -0·9 to -0·58), indicating a slight advantage in favor of colonoscopy. The comparison between colonoscopy and capsule returned a Hedges' g of 0·44 (95% CI of 0·20-0·69), indicating that delivery of the FMT by capsule was statistically significantly more effective. FMT provides an effective and safe treatment for C. difficile diarrhea. Further research into the efficacy of different preparation protocols is needed.}, }
@article {pmid33864057, year = {2021}, author = {Zipkin, M}, title = {Fecal microbiota potentiate checkpoint inhibitors, unleash microbiome startups.}, journal = {Nature biotechnology}, volume = {39}, number = {5}, pages = {529-532}, doi = {10.1038/d41587-021-00002-w}, pmid = {33864057}, issn = {1546-1696}, mesh = {*Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Microbiota/genetics ; Neoplasms/microbiology/*therapy ; }, }
@article {pmid33863898, year = {2021}, author = {Li, X and Su, C and Jiang, Z and Yang, Y and Zhang, Y and Yang, M and Zhang, X and Du, Y and Zhang, J and Wang, L and Jiang, J and Hong, B}, title = {Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome.}, journal = {NPJ biofilms and microbiomes}, volume = {7}, number = {1}, pages = {36}, pmid = {33863898}, issn = {2055-5008}, mesh = {Animals ; Atherosclerosis/*etiology/*metabolism/pathology ; Berberine/*pharmacology ; Choline/*adverse effects ; Diet ; Disease Models, Animal ; Disease Susceptibility ; Dysbiosis ; Gastrointestinal Microbiome/*drug effects ; Methylamines/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout, ApoE ; }, abstract = {Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.}, }
@article {pmid33863483, year = {2021}, author = {Albuhairi, S and Rachid, R}, title = {Biologics and Novel Therapies for Food Allergy.}, journal = {Immunology and allergy clinics of North America}, volume = {41}, number = {2}, pages = {271-283}, doi = {10.1016/j.iac.2021.01.002}, pmid = {33863483}, issn = {1557-8607}, mesh = {Allergens ; *Biological Products/therapeutic use ; Child ; *Food Hypersensitivity/therapy ; Humans ; Omalizumab/therapeutic use ; Quality of Life ; }, abstract = {Food allergy is a significant public health burden affecting around 10% of adults and 8% of children. Although the first peanut oral immunotherapy product received Food and Drug Administration approval in 2020, there is still an unmet need for more effective therapeutic options that minimize the risk of anaphylaxis, nutritional deficiencies, and patient's quality of life. Biologics are promising modalities, as they may improve compliance, target multiple food allergies, and treat other concomitant atopic diseases. Although omalizumab has been evaluated extensively, most biologics are more novel and have broader immunologic impact. Careful evaluation of their safety profile should therefore be conducted.}, }
@article {pmid33856727, year = {2021}, author = {Khanna, S}, title = {Microbiota restoration for recurrent Clostridioides difficile: Getting one step closer every day!.}, journal = {Journal of internal medicine}, volume = {290}, number = {2}, pages = {294-309}, doi = {10.1111/joim.13290}, pmid = {33856727}, issn = {1365-2796}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Recurrence ; }, abstract = {Clostridioides difficile infection (CDI) is an urgent health threat being the most common healthcare-associated infection, and its management is a clinical conundrum. Over 450 000 infections are seen in the United States with similar incidence seen in the rest of the developed world. The majority of infections seen are mild-moderate with fulminant disease and mortality being rare complications seen in the elderly and in those with comorbidities. The most common complication of CDI is recurrent infection with rates as high as 60% after three or more infections. A dilemma in the management of primary and recurrent CDI is testing due to the high sensitivity of the nucleic acid amplification tests such as the polymerase chain reaction, which leads to clinical false positives if patients are not chosen carefully (with symptoms) before testing. A newer testing regimen involving a 2-step strategy is emerging using glutamate dehydrogenase as a screening strategy followed by enzyme immunoassay for the C. difficile toxin. Microbiota restoration therapies are the cornerstone of management of recurrent CDI to prevent future recurrences. The most common modality of microbiota restoration is faecal microbiota transplantation, which has been tainted with heterogeneity and adverse events such as serious infectious transmission. The success rates for recurrence prevention from microbiota restoration therapies are over 90% compared with less than 50% of recurrence prevention with courses of antibiotics. This has led to development and emergence of standardized microbiota restoration therapies in capsule and enema forms. Capsule-based therapies include CP101 (positive phase II results), RBX7455 (positive phase I results), SER-109 (positive phase III results) and VE303 (ongoing phase II trial). Enema-based therapy includes RBX2660 (positive phase III data). This review summarizes the principles of management and diagnosis of CDI and focuses on emerging and existing data on faecal microbiota transplantation and standardized microbiota restoration therapies.}, }
@article {pmid33856024, year = {2021}, author = {Wang, Q and Luo, Y and Ray Chaudhuri, K and Reynolds, R and Tan, EK and Pettersson, S}, title = {The role of gut dysbiosis in Parkinson's disease: mechanistic insights and therapeutic options.}, journal = {Brain : a journal of neurology}, volume = {144}, number = {9}, pages = {2571-2593}, doi = {10.1093/brain/awab156}, pmid = {33856024}, issn = {1460-2156}, mesh = {Brain-Gut Axis/drug effects/*physiology ; Dysbiosis/immunology/*metabolism/*therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Parkinson Disease/immunology/*metabolism/*therapy ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; }, abstract = {Parkinson's disease is a common neurodegenerative disorder in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alterations in the gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the CNS, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries about alterations to the gut microbiota in Parkinson's disease and focus on current mechanistic insights into the microbiota-gut-brain axis in disease pathophysiology. Moreover, we discuss the interactions between the production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we draw attention to diet modification, the use of probiotics and prebiotics and faecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.}, }
@article {pmid33853794, year = {2021}, author = {Wieszczy, P and Kaminski, MF and Løberg, M and Bugajski, M and Bretthauer, M and Kalager, M}, title = {Estimation of overdiagnosis in colorectal cancer screening with sigmoidoscopy and faecal occult blood testing: comparison of simulation models.}, journal = {BMJ open}, volume = {11}, number = {4}, pages = {e042158}, pmid = {33853794}, issn = {2044-6055}, mesh = {*Colorectal Neoplasms/diagnosis/epidemiology ; Early Detection of Cancer ; Humans ; Mass Screening ; Medical Overuse ; Norway ; *Occult Blood ; Sigmoidoscopy ; }, abstract = {OBJECTIVE: To estimate overdiagnosis of colorectal cancer (CRC) for screening with sigmoidoscopy and faecal occult blood testing (FOBT).<br><br>DESIGN: Simulation study using data from randomised trials.<br><br>SETTING: Primary screening, UK, Norway PARTICIPANTS: 152&#x2009;850 individuals from the Nottingham trial and 98&#x2009;678 individuals from the Norwegian Colorectal Cancer Prevention (NORCCAP) trial.<br><br>INTERVENTION: CRC screening.<br><br>OUTCOME MEASURE: We estimated overdiagnosis using long-term data from two randomised trials: the Nottingham trial comparing FOBT screening every other year to no-screening, and the NORCCAP trial comparing once-only sigmoidoscopy screening to no-screening. To estimate the natural growth of adenomas to CRC, we used the following microsimulation models: (i) the Microsimulation Screening Analysis; (ii) the CRC Simulated Population model for Incidence and Natural history; (iii) the Simulation Model of Colorectal Cancer; (iv) a model derived by the German Cancer Research Center. We defined overdiagnosed cancers as the difference between the observed number of CRCs in the no-screening arm and the expected number of cancers in screening arm (sum of observed and prevented by adenoma removal). The amount of overdiagnosis is defined as the number of overdiagnosed cancers over the number of cancers observed in the no-screening arm.<br><br>RESULTS: Overdiagnosis estimates were highly dependent on model assumptions. For FOBT screening with 2354 cancers observed in control arm, four out of five models predicted overdiagnosis, range 2.0% (2400 cancers expected in screening) to 7.6% (2533 cancers expected in screening). For sigmoidoscopy screening with 452 cancers observed in control arm, all models predicted overdiagnosis, range 25.2% (566 cancers expected in screening) to 128.1% (1031 cancers expected in screening).<br><br>CONCLUSIONS: The amount of overdiagnosis estimated based on the microsimulation models varied substantially. Microsimulation models may not give reliable estimates of the preventive effect of adenoma removal, and should be used with caution to inform guidelines.}, }
@article {pmid33852207, year = {2021}, author = {Ballif, A and Gerber, S and Carrez, L and Audry, M and Sadeghipour, F and Mitouassiwou, A and Croxatto, A and Opota, O and Prod'hom, G and Henchoz, S and Schoepfer, A and Cavassini, M and Galpérine, T}, title = {[Fecal microbiota transplantation: from the evidence to the realty of the field].}, journal = {Revue medicale suisse}, volume = {17}, number = {734}, pages = {726-731}, pmid = {33852207}, issn = {1660-9379}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {In clinical practice, fecal microbiota transplantation (FMT) has been established as an unparalleled therapy to date for multiple recurrent Clostridioides difficile infections (CDI). The implementation of the FMT in practice requires a significant investment to meet legal, security and financial requirements. Research on the microbiota is booming and multiple investigations on FMT in indications other than CDI are ongoing.}, }
@article {pmid33851215, year = {2021}, author = {Cappetto, CM}, title = {Successful use of early, repeat fecal microbiota transplantation for initial treatment of severe, refractory Clostridioides difficile colitis.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {78}, number = {15}, pages = {1374-1381}, pmid = {33851215}, issn = {1535-2900}, mesh = {Aged ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; *Colitis/therapy ; Fecal Microbiota Transplantation ; Humans ; Male ; Recurrence ; Treatment Outcome ; }, abstract = {PURPOSE: There is a paucity of literature surrounding the use of early fecal microbiota transplantation (FMT) for patients presenting with an initial episode of severe, refractory Clostridioides difficile infection (CDI). Information on optimal antibiotic dosing and therapy duration surrounding FMT during an acute, initial episode of CDI is also limited. Described here is a case of successful treatment of CDI after 4 FMTs during an acute, initial episode of severe, refractory Clostridioides difficile colitis.<br><br>SUMMARY: A 69-year-old community-dwelling, Caucasian male presented after 48 hours of vomiting and diarrhea. A stool sample was collected and resulted positive for Clostridioides difficile by both polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). The patient was treated with several days of oral and rectal vancomycin therapy in addition to intravenous metronidazole, but those treatments failed. His clinical and nutrition status deteriorated over the course of several days until salvage therapy was ordered, with administration of 1 inpatient nasogastric FMT and 1 inpatient colonoscopic FMT followed by outpatient colonoscopic FMTs on 2 consecutive days within 2 weeks of hospital discharge.<br><br>CONCLUSION: This case suggests a role for early, repeat FMT during an initial presentation of a severe Clostridioides difficile colitis episode refractory to pharmacologic antimicrobial therapy. It also adds to emerging literature regarding the timing of antibiotic cessation surrounding FMT.}, }
@article {pmid33849559, year = {2021}, author = {Gong, S and Feng, Y and Zeng, Y and Zhang, H and Pan, M and He, F and Wu, R and Chen, J and Lu, J and Zhang, S and Yuan, S and Chen, X}, title = {Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {147}, pmid = {33849559}, issn = {1479-5876}, mesh = {Animals ; Cisplatin/adverse effects ; *Gastrointestinal Microbiome ; Inflammation ; Liver ; Mice ; Oxidative Stress ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Gut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown.<br><br>METHODS: We compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment.<br><br>RESULTS: 16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity.<br><br>CONCLUSIONS: This study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.}, }
@article {pmid33847139, year = {2021}, author = {Khanna, S and Kraft, CS}, title = {The interplay of SARS-CoV-2 and Clostridioides difficile infection.}, journal = {Future microbiology}, volume = {16}, number = {}, pages = {439-443}, pmid = {33847139}, issn = {1746-0921}, mesh = {*COVID-19/epidemiology/transmission ; Clostridioides difficile/isolation &amp; purification ; *Clostridium Infections/diagnosis/epidemiology/therapy ; *Coinfection/diagnosis/epidemiology ; Cross Infection/*prevention &amp; control ; Fecal Microbiota Transplantation ; *Feces/microbiology/virology ; Humans ; Infection Control ; Pandemics/*prevention &amp; control ; SARS-CoV-2/isolation &amp; purification ; }, abstract = {The COVID-19 pandemic has changed the way we practice medicine and lead our lives. In addition to pulmonary symptoms; COVID-19 as a syndrome has multisystemic involvement including frequent gastrointestinal symptoms such as diarrhea. Due to microbiome alterations with COVID-19 and frequent antibiotic exposure, COVID-19 can be complicated by Clostridioides difficile infection. Co-infection with these two can be associated with a high risk of complications. Infection control measures in hospitals is enhanced due to the COVID-19 pandemic which in turn appears to reduce the incidence of hospital-acquired infections such as C. difficile infection. Another implication of COVID-19 and its potential transmissibility by stool is microbiome-based therapies. Potential stool donors should be screened COVID-19 symptoms and be tested for COVID-19.}, }
@article {pmid33846008, year = {2021}, author = {Litta, F and Bracchitta, S and Naldini, G and Mistrangelo, M and Tricomi, N and La Torre, M and Altomare, DF and Mozzon, M and Testa, A and Zigiotto, D and Sica, G and Tutino, R and Lisi, G and Marino, F and Luglio, G and Vergari, R and Terrosu, G and Cantarella, F and Foti, N and Giuliani, A and Moroni, R and Ratto, C and , }, title = {FISSIT (Fistula Surgery in Italy) study: A retrospective survey on the surgical management of anal fistulas in Italy over the last 15 years.}, journal = {Surgery}, volume = {170}, number = {3}, pages = {689-695}, doi = {10.1016/j.surg.2021.02.055}, pmid = {33846008}, issn = {1532-7361}, mesh = {Anal Canal/*surgery ; Fecal Incontinence/*epidemiology/etiology ; Female ; Follow-Up Studies ; *Forecasting ; Humans ; Incidence ; Italy/epidemiology ; Male ; Middle Aged ; Population Surveillance/*methods ; Postoperative Complications/*epidemiology/etiology ; Rectal Fistula/complications/epidemiology/*surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: Surgical treatment of anal fistulas is still a challenge. The aims of this study were to evaluate the adoption and healing rates for the different surgical techniques used in Italy over the past 15 years.<br><br>METHODS: This was a multicenter retrospective observational study of patients affected by simple and complex anal fistulas of cryptoglandular origin who were surgically treated in the period 2003-2017. Surgical techniques were grouped as sphincter-cutting or sphincter-sparing and as technology-assisted or techno-free. All patients included in the study were followed for at least 12 months.<br><br>RESULTS: A total of 9,536 patients (5,520 simple; 4,016 complex fistulas) entered the study. For simple fistulas, fistulotomy was the most frequently used procedure, although its adoption significantly decreased over the years (P < .0005), with an increase in sphincter-sparing approaches; the overall healing rate in simple fistulas was 81.1%, with a significant difference between sphincter-cutting (91.9%) and sphincter-sparing (65.1%) techniques (P&#xa0;= .001). For complex fistulas, the adoption of sphincter-cutting approaches decreased, while sphincter-sparing techniques were mildly preferred (P < .0005). Moreover, there was a significant trend toward the use of technology-assisted procedures. The overall healing rate for complex fistulas was 69.0%, with a measurable difference between sphincter-cutting (81.1%) and sphincter-sparing (61.4%; P&#xa0;= .001) techniques and between techno-free and technology-assisted techniques (72.5% and 55.0%, respectively; P&#xa0;= .001).<br><br>CONCLUSION: Surgical treatment of anal fistulas has changed, with a trend toward the use of sphincter-sparing techniques. The overall cure rate has remained stable, even if the most innovative procedures have achieved a lower success rate.}, }
@article {pmid33844988, year = {2021}, author = {Monaghan, TM and Seekatz, AM and Markham, NO and Yau, TO and Hatziapostolou, M and Jilani, T and Christodoulou, N and Roach, B and Birli, E and Pomenya, O and Louie, T and Lacy, DB and Kim, P and Lee, C and Kao, D and Polytarchou, C}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection Associates With Functional Alterations in Circulating microRNAs.}, journal = {Gastroenterology}, volume = {161}, number = {1}, pages = {255-270.e4}, pmid = {33844988}, issn = {1528-0012}, support = {T32 DK007673/DK/NIDDK NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; K01 DK111794/DK/NIDDK NIH HHS/United States ; I01 BX002943/BX/BLRD VA/United States ; R01 AI095755/AI/NIAID NIH HHS/United States ; R37 AI095755/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Circulating MicroRNA/*blood/genetics ; Clostridium Infections/blood/genetics/microbiology/*therapy ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Male ; Middle Aged ; Randomized Controlled Trials as Topic ; *Reinfection ; Tissue Culture Techniques ; Transcriptome ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: The molecular mechanisms underlying successful fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) remain poorly understood. The primary objective of this study was to characterize alterations in microRNAs (miRs) following FMT for rCDI.<br><br>METHODS: Sera from 2 prospective multicenter randomized controlled trials were analyzed for miRNA levels with the use of the Nanostring nCounter platform and quantitative reverse-transcription (RT) polymerase chain reaction (PCR). In addition, rCDI-FMT and toxin-treated animals and ex&#xa0;vivo human colonoids were used to compare intestinal tissue and circulating miRs. miR inflammatory gene targets in colonic epithelial and peripheral blood mononuclear cells were evaluated by quantitative PCR (qPCR) and 3'UTR reporter assays. Colonic epithelial cells were used for mechanistic, cytoskeleton, cell growth, and apoptosis studies.<br><br>RESULTS: miRNA profiling revealed up-regulation of 64 circulating miRs 4 and 12 weeks after FMT compared with screening, of which the top 6 were validated in the discovery cohort by means of RT-qPCR. In a murine model of relapsing-CDI, RT-qPCR analyses of sera and cecal RNA extracts demonstrated suppression of these miRs, an effect reversed by FMT. In mouse colon and human colonoids, C difficile toxin B (TcdB) mediated the suppressive effects of CDI on miRs. CDI dysregulated DROSHA, an effect reversed by FMT. Correlation analyses, qPCR ,and 3'UTR reporter assays revealed that miR-23a, miR-150, miR-26b, and miR-28 target directly the 3'UTRs of IL12B, IL18, FGF21, and TNFRSF9, respectively. miR-23a and miR-150 demonstrated cytoprotective effects against TcdB.<br><br>CONCLUSIONS: These results provide novel and provocative evidence that modulation of the gut microbiome via FMT induces alterations in circulating and intestinal tissue miRs. These findings contribute to a greater understanding of the molecular mechanisms underlying FMT and identify new potential targets for therapeutic intervention in rCDI.}, }
@article {pmid33840331, year = {2021}, author = {Madsen, M and Kimer, N and Bendtsen, F and Petersen, AM}, title = {Fecal microbiota transplantation in hepatic encephalopathy: a systematic review.}, journal = {Scandinavian journal of gastroenterology}, volume = {56}, number = {5}, pages = {560-569}, doi = {10.1080/00365521.2021.1899277}, pmid = {33840331}, issn = {1502-7708}, mesh = {Ammonia ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; *Hepatic Encephalopathy/therapy ; Humans ; *Microbiota ; Treatment Outcome ; }, abstract = {Hepatic encephalopathy (HE) is a reversible neurocognitive dysfunction that ranges in severity from subclinical alterations to coma. Patients with chronic liver disease are predisposed to HE due to metabolic failure and portosystemic shunting of toxins, of which ammonia is believed to be the main toxic chemical. Fecal microbiota transplantation (FMT) may reduce ammonia synthesis by altering the gut microbiota composition to a taxon low in urease, diminish uptake of ammonia by reestablishing the integrity of the intestinal barrier and increase ammonia clearance by improving liver function. In this systematic review, we summarize the insights of the current literature examining FMT as a treatment for HE.PubMed and EMBASE were searched on 08 February 2021 using the MeSH terms 'fecal microbiota transplantation &amp; hepatic encephalopathy' and the abbreviations 'FMT &amp; HE'.Eight studies fulfilled our inclusion criteria, comprising two randomized clinical trials, three case reports and three rodent studies. Thirty-nine patients with HE were treated with FMT. Thirty-nine rodents received FMT in laboratory tests. FMT improved neurocognitive test results in four human studies and two rodent studies. Microbiota originating from donors was found in human recipients one year post-FMT. Readmission of patients was lower after treatment with FMT compared to standard of care.FMT may improve neurocognitive function and reduce serious adverse events in patients with HE, but the studies conducted so far have been small and their long-term follow-up is limited. Large-scale, randomized and controlled trials are needed to validate and help standardize the clinical application of FMT in cases of HE.}, }
@article {pmid33836037, year = {2021}, author = {Björkqvist, O and Rangel, I and Serrander, L and Magnusson, C and Halfvarson, J and Norén, T and Bergman-Jungeström, M}, title = {Faecalibacterium prausnitzii increases following fecal microbiota transplantation in recurrent Clostridioides difficile infection.}, journal = {PloS one}, volume = {16}, number = {4}, pages = {e0249861}, pmid = {33836037}, issn = {1932-6203}, mesh = {Aged ; Bacteria/genetics/isolation &amp; purification ; Clostridium Infections/*therapy ; DNA, Bacterial/genetics/metabolism ; Faecalibacterium prausnitzii/*isolation &amp; purification ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Recurrence ; }, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant's causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce.<br><br>METHODS: Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction.<br><br>RESULTS: The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001).<br><br>CONCLUSIONS: FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.}, }
@article {pmid33834162, year = {2020}, author = {Grigoryan, Z and Shen, MJ and Twardus, SW and Beuttler, MM and Chen, LA and Bateman-House, A}, title = {Fecal microbiota transplantation: Uses, questions, and ethics.}, journal = {Medicine in microecology}, volume = {6}, number = {}, pages = {}, pmid = {33834162}, issn = {2590-0978}, support = {K23 DK119544/DK/NIDDK NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) has rapidly grown in notoriety and popularity worldwide as a treatment for both recurrent and refractory C. difficile infection (CDI), as well as for a myriad of other indications, with varying levels of evidence to justify its use. At present, FMT use in the U.S. has not received marketing approval from the U.S. Food and Drug Administration (FDA), but is permitted under "enforcement discretion" for CDI not responding to standard therapy. Meanwhile, the rising interest in the gut microbiome throughout mainstream media has paved the way for "do-it-yourself" (DIY) adaptations of the procedure. This access and unregulated use, often outside any clinical supervision, has quickly outpaced the medical community's research and regulatory efforts. While some studies have been able to demonstrate the success of FMT in treating conditions other than CDI-studies on ulcerative colitis have been particularly promising-little is still known about the treatmen's mechanism of action or long-term side effects. Likewise, screening of donor stool is in its early stages in terms of protocol standardization. In this paper, we explore the regulatory and ethical concerns that arise from the need to balance access to a nascent but promising innovative treatment with the need for research into its efficacy, risk profile, and long-term impact.}, }
@article {pmid33832129, year = {2021}, author = {Fang, S and Wu, S and Ji, L and Fan, Y and Wang, X and Yang, K}, title = {The combined therapy of fecal microbiota transplantation and laxatives for functional constipation in adults: A systematic review and meta-analysis of randomized controlled trials.}, journal = {Medicine}, volume = {100}, number = {14}, pages = {e25390}, pmid = {33832129}, issn = {1536-5964}, support = {112123A12201/001/002//Graduate Science Research Fund of Zhejiang Chinese Medical University/ ; }, mesh = {Adult ; Aged ; Case-Control Studies ; China/epidemiology ; Combined Modality Therapy/adverse effects/*methods ; Constipation/*physiopathology/psychology/*therapy ; Data Management ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Humans ; Laxatives/adverse effects/*therapeutic use ; Male ; Middle Aged ; Quality of Life ; Randomized Controlled Trials as Topic ; Safety ; Treatment Outcome ; }, abstract = {OBJECTIVE: Functional constipation is a prevalent, burdensome gastrointestinal disorder whose treatment remains challenging. Combined therapy uniting multiple treatments may be promising. Fecal microbiota transplantation (FMT) which tends to be an etiological treatment has been increasingly investigated in its management. Meanwhile, laxatives are widely used to relieve constipation temporarily, but their overall efficacy is poor. Therefore, we performed meta-analyses of randomized controlled trials to evaluate the joint efficacy of FMT and laxatives in functional constipation.<br><br>METHODS: We performed a systematic literature search of 6 electronic databases as of August 11, 2020. Randomized controlled trial of FMT together with laxatives vs laxatives alone in functional constipation in adults were included. Two reviewers independently performed the screening, data extraction, and bias assessment. Dichotomous outcome data were synthesized by risk ratio, and measurement data by weighted mean difference (WMD).<br><br>RESULTS: A total of 1400 records were identified, of which 5 were eligible (409 patients). Overall, compared to laxatives alone, combined therapy of FMT and laxatives more significantly improved total effective rate (risk ratio: 1.35; 95% confidence interval [CI]: 1.14, 1.60; I2&#x200a;=&#x200a;13%), Bristol stool form scale score (WMD: 1.04; 95% CI: 0.57, 1.51; I2&#x200a;=&#x200a;76%), reduce Wexner score (WMD: -3.25; 95% CI: -5.58, -0.92; I2&#x200a;=&#x200a;92%), Knowles-Eccersley-Scott-Symptom (KESS) score (WMD: -5.65; 95% CI: -7.62, -3.69; I2&#x200a;=&#x200a;0%) and patient assessment of constipation quality of life score (WMD: -18.56; 95%; CI: -26.43, -10.68; I2&#x200a;=&#x200a;78%). No serious adverse events were reported. The majority of included studies had poor methodological quality.<br><br>CONCLUSION: Combined therapy of FMT and laxatives may be a reasonably effective and safe treatment for people with functional constipation. However, caution is needed with the interpretation of these data due to the small sample size, high heterogeneity, and low quality of the studies. Besides, we expect that more studies will be performed exploring the efficacy and safety of combined therapy for functional constipation.}, }
@article {pmid33827161, year = {2021}, author = {Dixon, CE and Bedenice, D and Restifo, M and Mazan, M and Brewer, P and Knafo, SE}, title = {NEONATAL INTENSIVE CARE OF 10 HOSPITALIZED GIRAFFE CALVES (GIRAFFA CAMELOPARDALIS) REQUIRING HAND-REARING.}, journal = {Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians}, volume = {52}, number = {1}, pages = {57-66}, doi = {10.1638/2019-0021}, pmid = {33827161}, issn = {1042-7260}, mesh = {Animal Husbandry/*methods ; Animals ; *Animals, Newborn ; Critical Care/*methods ; Female ; *Giraffes ; Hospitals, Animal ; Male ; Retrospective Studies ; }, abstract = {This retrospective case series describes the clinicopathologic findings, diagnoses, treatment, and outcomes of 10 hand-reared newborn giraffe (Giraffa camelopardalis) calves admitted to a university teaching hospital for intensive care. Ten calves (five males, five females; nine reticulated giraffes [Giraffa camelopardalis reticulata], one Masai giraffe [G. c. tippelskirchi]), were admitted under 2 days of age. Inadequate transfer of passive immunity was suspected in 5 of 10 calves based on assessment of serum total solids and globulin values. These calves were treated with oral frozen bovine colostrum and/or intravenous hyperimmune bovine plasma. Diarrhea occurred in 6 of 10 calves and was managed with supportive care, fecal microbiota transplantation, and limiting milk intake (offering 10% body weight [BW] in milk per day, while feeding <2 L per meal at 2- to 4-hr intervals). Less common diagnoses included pneumonia (n = 3) and mycoplasma-associated septic arthritis (n = 1). Eight calves received systemic antimicrobial therapy. Hyperlactatemia (lactate > 5 mmol/L; n = 8) and hypercreatininemia (creatinine > 2.0 mg/dl, n = 7) were the most common presenting laboratory abnormalities, which resolved with intravenous fluid therapy. All neonatal giraffes survived to discharge after a median hospitalization of 9.5 days (range, 5-37 days) and were successfully hand-reared at their place of birth. In conclusion, neonatal giraffe calves can be intensively managed in a hospital environment. Diarrhea was a common clinical problem and can be related to feeding regimens. Intravenous hyperimmune bovine plasma infusion was well tolerated to manage failure of transfer of passive immunity in calves with inadequate colostrum administration. The current study supports that compromised neonatal giraffe calves may carry an excellent prognosis after early, intensive intervention.}, }
@article {pmid33827154, year = {2021}, author = {Park, SY and Seo, GS}, title = {Fecal Microbiota Transplantation: Is It Safe?.}, journal = {Clinical endoscopy}, volume = {54}, number = {2}, pages = {157-160}, pmid = {33827154}, issn = {2234-2400}, abstract = {Fecal microbiota transplantation (FMT) is an accepted procedure for the management of recurrent Clostridioides difficile infections. FMT is generally considered safe and well-tolerated - even in high-risk patients. Most short-term risks are mild and known to be associated with delivery methods. Long-term side effects have not been established, and no signs of harm have been found to date. However, causality for several microbiome-associated diseases has to be established. Even though FMT is generally considered safe with strict donor screening, serious adverse events have been recently associated with the FMT product from the stool bank, where screening for multi-drug resistant organisms is not included in protocols. Here, we discuss the adverse events associated with FMT and safety issues.}, }
@article {pmid33825149, year = {2021}, author = {Liang, Y and Cui, L and Gao, J and Zhu, M and Zhang, Y and Zhang, HL}, title = {Gut Microbial Metabolites in Parkinson's Disease: Implications of Mitochondrial Dysfunction in the Pathogenesis and Treatment.}, journal = {Molecular neurobiology}, volume = {58}, number = {8}, pages = {3745-3758}, pmid = {33825149}, issn = {1559-1182}, support = {81974194//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Brain/*metabolism ; Brain-Gut Axis/*physiology ; Dysbiosis/genetics/metabolism/therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Mitochondria/genetics/*metabolism ; Parkinson Disease/genetics/*metabolism/*therapy ; Probiotics/therapeutic use ; Treatment Outcome ; Ubiquitin-Protein Ligases/genetics/metabolism ; }, abstract = {The search for therapeutic targets for Parkinson's disease (PD) is hindered by the incomplete understanding of the pathophysiology of the disease. Mitochondrial dysfunction is an area with high potential. The neurobiological signaling connections between the gut microbiome and the central nervous system are incompletely understood. Multiple lines of evidence suggest that the gut microbiota participates in the pathogenesis of PD. Gut microbial dysbiosis may contribute to the loss of dopaminergic neurons through mitochondrial dysfunction. The intervention of gut microbial metabolites via the microbiota-gut-brain axis may serve as a promising therapeutic strategy for PD. In this narrative review, we summarize the potential roles of gut microbial dysbiosis in PD, with emphasis on microbial metabolites and mitochondrial function. We then review the possible ways in which microbial metabolites affect the central nervous system, as well as the impact of microbial metabolites on mitochondrial dysfunction. We finally discuss the possibility of gut microbiota as a therapeutic target for PD.}, }
@article {pmid33824200, year = {2021}, author = {Xiao, L and Yan, J and Yang, T and Zhu, J and Li, T and Wei, H and Chen, J}, title = {Fecal Microbiome Transplantation from Children with Autism Spectrum Disorder Modulates Tryptophan and Serotonergic Synapse Metabolism and Induces Altered Behaviors in Germ-Free Mice.}, journal = {mSystems}, volume = {6}, number = {2}, pages = {}, pmid = {33824200}, issn = {2379-5077}, abstract = {To determine the relationship of the gut microbiota and its metabolites with autism spectrum disorder (ASD)-like behaviors and preliminarily explore the potential molecular mechanisms, the fecal microbiota from donors with ASD and typically developing (TD) donors were transferred into germ-free (GF) mice to obtain ASD-FMT mice and TD-FMT mice, respectively. Behavioral tests were conducted on these mice after 3 weeks. 16S rRNA gene sequencing of the cecal contents and untargeted metabolomic analysis of the cecum, serum, and prefrontal cortex were performed. Untargeted metabolomics was also used to analyze fecal samples of TD and ASD children. Western blotting detected the protein expression levels of tryptophan hydroxylase 1 (TPH1), serotonin transporter (SERT), and serotonin 1A receptor (5-HT1AR) in the colon and TPH2, SERT, and 5-HT1AR in the prefrontal cortex of mice. ASD-FMT mice showed ASD-like behavior and a microbial community structure different from that of TD-FMT mice. Tryptophan and serotonin metabolisms were altered in both ASD and TD children and ASD-FMT and TD-FMT mice. Some microbiota may be related to tryptophan and serotonin metabolism. Compared with TD-FMT mice, ASD-FMT mice showed low SERT and 5-HT1AR and high TPH1 expression levels in the colon. In the prefrontal cortex, the expression levels of TPH2 and SERT were increased in the ASD-FMT group relative to the TD-FMT group. Therefore, the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. These changes may be related to changes in some key proteins involved in the synthesis and transport of serotonin.IMPORTANCE The relationship between the gut microbiota and ASD is not yet fully understood. Numerous studies have focused on the differences in intestinal microbial and metabolism profiles between TD and ASD children. However, it is still not clear if these microbes and metabolites cause the development of ASD symptoms. Here, we collected fecal samples from TD and ASD children, transplanted them into GF mice, and found that the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. We also demonstrated that tryptophan and serotonin metabolism was also altered in ASD and TD children. Together, these findings confirm that the microbiome from children with ASD may lead to ASD-like behavior of GF mice through metabolites, especially tryptophan and serotonin metabolism.}, }
@article {pmid33822669, year = {2021}, author = {Singh, TP and Natraj, BH}, title = {Next-generation probiotics: a promising approach towards designing personalized medicine.}, journal = {Critical reviews in microbiology}, volume = {47}, number = {4}, pages = {479-498}, doi = {10.1080/1040841X.2021.1902940}, pmid = {33822669}, issn = {1549-7828}, mesh = {Animals ; Dysbiosis/*drug therapy/microbiology ; Gastrointestinal Microbiome/drug effects ; Humans ; Prebiotics/administration &amp; dosage ; Precision Medicine/*trends ; Probiotics/*administration &amp; dosage ; }, abstract = {Second brain, forgotten organ, individual's identity card, and host's fingerprint are the few collective terms that are often used to describe the gut microbiome because of its variability, accountability, and its role in deciding the host's health. Also, the understanding of this host health-gut microbiota relationship can create an opportunity to control an individual's health by manipulating the gut microbiota composition. Several approaches like administration of probiotic, prebiotics, synbiotics, faecal microbiota transplantation have been tried to mitigate the dysbiosis originated ill effects. But the effects of these approaches are highly generic and non-specific. This creates the necessity to design personalized medicine that focuses on treatment of specific disease considering the individual specific gut microbiome. The health promoting commensals could be the new promising prophylactic and therapeutic agents for designing personalized medicine. These commensals are designated as next-generation probiotics (NGPs) and their unusual characteristics, unknown identity and special growth requirements have presented difficulties for researcher, industrial exploitation, and regulatory agencies. In this perspective, this review discusses the concept of NGPs, NGP candidates as tool for designing personalized medicine, designer probiotics as NGPs, required regulatory framework, and propose a road map to develop the NGP based product.}, }
@article {pmid33821247, year = {2021}, author = {Coryell, MP and Iakiviak, M and Pereira, N and Murugkar, PP and Rippe, J and Williams, DB and Heald-Sargent, T and Sanchez-Pinto, LN and Chavez, J and Hastie, JL and Sava, RL and Lien, CZ and Wang, TT and Muller, WJ and Fischbach, MA and Carlson, PE}, title = {A method for detection of SARS-CoV-2 RNA in healthy human stool: a validation study.}, journal = {The Lancet. Microbe}, volume = {2}, number = {6}, pages = {e259-e266}, pmid = {33821247}, issn = {2666-5247}, mesh = {*COVID-19/diagnosis ; Humans ; Pandemics ; RNA, Viral/genetics ; Reproducibility of Results ; *SARS-CoV-2/genetics ; }, abstract = {BACKGROUND: Faecal shedding of SARS-CoV-2 has raised concerns about transmission through faecal microbiota transplantation procedures. Validation parameters of authorised tests for SARS-CoV-2 RNA detection in respiratory samples are described in product labelling, whereas the published methods for SARS-CoV-2 detection from faecal samples have not permitted a robust description of the assay parameters. We aimed to develop and validate a test specifically for detection of SARS-CoV-2 in human stool.<br><br>METHODS: In this validation study, we evaluated performance characteristics of a reverse transcriptase real-time PCR (RT-rtPCR) test for detection of SARS-CoV-2 in human stool specimens by spiking stool with inactivated SARS-CoV-2 material. A modified version of the US Centers for Disease Control and Prevention RT-rtPCR SARS-CoV-2 test was used for detection of viral RNA. Analytical sensitivity was evaluated in freshly spiked stool by testing two-fold dilutions in replicates of 20. Masked samples were tested by a second laboratory to evaluate interlaboratory reproducibility. Short-term (7-day) stability of viral RNA in stool samples was assessed with four different stool storage buffers (phosphate-buffered saline, Cary-Blair medium, Stool Transport and Recovery [STAR] buffer, and DNA/RNA Shield) kept at -80&#xb0;C, 4&#xb0;C, and ambient temperature (approximately 21&#xb0;C). We also tested clinical stool and anal swab specimens from patients who were SARS-CoV-2 positive by nasopharyngeal testing.<br><br>FINDINGS: The lower limit of detection of the assay was found to be 3000 viral RNA copies per g of original stool sample, with 100% detection across 20 replicates assessed at this concentration. Analytical sensitivity was diminished by approximately two times after a single freeze-thaw cycle at -80&#xb0;C. At 100 times the limit of detection, spiked samples were generally stable in all four stool storage buffers tested for up to 7 days, with maximum changes in mean threshold cycle values observed at -80&#xb0;C storage in Cary-Blair medium (from 29&#xb7;4 [SD 0&#xb7;27] at baseline to 30&#xb7;8 [0&#xb7;17] at day 7; p<0&#xb7;0001), at 4&#xb0;C storage in DNA/RNA Shield (from 28&#xb7;5 [0&#xb7;15] to 29&#xb7;8 [0&#xb7;09]; p=0&#xb7;0019), and at ambient temperature in STAR buffer (from 30&#xb7;4 [0&#xb7;24] to 32&#xb7;4 [0&#xb7;62]; p=0&#xb7;0083). 30 contrived SARS-CoV-2 samples were tested by a second laboratory and were correctly identified as positive or negative in at least one of two rounds of testing. Additionally, SARS-CoV-2 RNA was detected using this assay in the stool and anal swab specimens of 11 of 23 individuals known to be positive for SARS-CoV-2.<br><br>INTERPRETATION: This is a sensitive and reproducible assay for detection of SARS-CoV-2 RNA in human stool, with potential uses in faecal microbiota transplantation donor screening, sewage monitoring, and further research into the effects of faecal shedding on the epidemiology of the COVID-19 pandemic.<br><br>FUNDING: National Institute of Allergy and Infectious Diseases, US National Institutes of Health; Center for Biologics Evaluation and Research, US Food and Drug Administration.}, }
@article {pmid33820996, year = {2021}, author = {Wilkinson, JE and Franzosa, EA and Everett, C and Li, C and ,  and ,  and Hu, FB and Wirth, DF and Song, M and Chan, AT and Rimm, E and Garrett, WS and Huttenhower, C}, title = {A framework for microbiome science in public health.}, journal = {Nature medicine}, volume = {27}, number = {5}, pages = {766-774}, pmid = {33820996}, issn = {1546-170X}, support = {C10674/A27140/CRUK_/Cancer Research UK/United Kingdom ; 27140/CRUK_/Cancer Research UK/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; P30 DK046200/DK/NIDDK NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; R01 NS097723/NS/NINDS NIH HHS/United States ; }, mesh = {Biomedical Research/*methods ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Health Status ; Humans ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; Public Health/education/*methods ; }, abstract = {Human microbiome science has advanced rapidly and reached a scale at which basic biology, clinical translation and population health are increasingly integrated. It is thus now possible for public health researchers, practitioners and policymakers to take specific action leveraging current and future microbiome-based opportunities and best practices. Here we provide an outline of considerations for research, education, interpretation and scientific communication concerning the human microbiome and public health. This includes guidelines for population-scale microbiome study design; necessary physical platforms and analysis methods; integration into public health areas such as epidemiology, nutrition, chronic disease, and global and environmental health; entrepreneurship and technology transfer; and educational curricula. Particularly in the near future, there are both opportunities for the incorporation of microbiome-based technologies into public health practice, and a growing need for policymaking and regulation around related areas such as prebiotic and probiotic supplements, novel live-cell therapies and fecal microbiota transplants.}, }
@article {pmid33814032, year = {2021}, author = {Compo, NR and Mieles-Rodriguez, L and Gomez, DE}, title = {Fecal Bacterial Microbiota of Healthy Free-Ranging, Healthy Corralled, and Chronic Diarrheic Corralled Rhesus Macaques (Macaca mulatta).}, journal = {Comparative medicine}, volume = {71}, number = {2}, pages = {152-165}, pmid = {33814032}, issn = {2769-819X}, support = {P40 OD012217/OD/NIH HHS/United States ; U42 OD021458/OD/NIH HHS/United States ; }, mesh = {Animals ; Feces ; *Gastrointestinal Microbiome ; Health Status ; Macaca mulatta ; RNA, Ribosomal, 16S/genetics ; }, abstract = {A clinical challenge to nearly every primate facility in North America is chronic idiopathic diarrhea (CID), the pathogenesis of which has yet to be fully elucidated. However, wild macaques appear resistant to CID, a trend that we observed in the free-ranging population of the Caribbean Primate Research Center. The gastrointestinal microbiota has been shown to have a significant role in the pathogenesis of disease and in maintaining normal health and development of the gut. In humans, chronic diarrhea is associated with alteration of the gut microbiota, which has lower bacterial diversity than does the microbiota of healthy humans. The current study was designed to describe and compare the fecal bacterial microbiota of healthy corralled, CID corralled, and healthy, free-ranging macaques. Fresh fecal samples were collected from healthy corralled (HC; n = 30) and CID (n = 27) rhesus macaques and from healthy macaques from our free-ranging colony (HF; n = 43). We excluded macaques that had received antibiotics during the preceding 60 d (90 d for healthy animals). Bacterial DNA was extracted, and the V4 region of the 16S rRNA gene was sequenced and compared with known databases. The relative abundance of Proteobacteria was higher in CID animals than HC animals, but otherwise few differences were found between these 2 groups. HF macaques were differentially enriched with Christensenellaceae and Helicobacter, which are highly associated with a 'healthy' gut in humans, as compared to corralled animals, whereas CID animals were enriched with Proteobacteria, which are associated with dysbiosis in other species. These results indicate that environment has a greater influence than health status on the gut microbiota. Furthermore, the current data provided targets for future studies on potential clinical interventions, such as probiotics and fecal transplants.}, }
@article {pmid33812983, year = {2022}, author = {Wang, F and Song, M and Lu, X and Zhu, X and Deng, J}, title = {Gut microbes in gastrointestinal cancers.}, journal = {Seminars in cancer biology}, volume = {86}, number = {Pt 2}, pages = {967-975}, doi = {10.1016/j.semcancer.2021.03.037}, pmid = {33812983}, issn = {1096-3650}, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Metagenomics ; *Gastrointestinal Neoplasms/etiology/therapy ; }, abstract = {Gut microbes (GMs), dominated by bacteria, play important roles in many physiological processes. The structures and functions of GMs are closely related to human health, the occurrence and development of diseases and the rapid recovery of the body. Gastrointestinal cancers are the major diseases affecting human health worldwide. With the development of metagenomic technology and the wide application of new generation sequencing technology, a large number of studies suggest that complex GMs are related to the occurrence and development of gastrointestinal cancers. Fecal microbiota transplantation (FMT) and probiotics can treat and prevent the occurrence of gastrointestinal cancers. This article reviews the latest research progress of microbes in gastrointestinal cancers from the perspectives of the correlation, the influence mechanism and the application, so as to provide new directions for the prevention, early diagnosis and treatment of gastrointestinal cancers.}, }
@article {pmid33809421, year = {2021}, author = {Kazemian, N and Kao, D and Pakpour, S}, title = {Fecal Microbiota Transplantation during and Post-COVID-19 Pandemic.}, journal = {International journal of molecular sciences}, volume = {22}, number = {6}, pages = {}, pmid = {33809421}, issn = {1422-0067}, mesh = {COVID-19/*epidemiology ; Clostridium Infections/therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Gastrointestinal Microbiome ; Humans ; Lung/physiopathology ; *Pandemics ; Treatment Outcome ; }, abstract = {COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut-lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe.}, }
@article {pmid33806843, year = {2021}, author = {Basson, AR and Cominelli, F and Rodriguez-Palacios, A}, title = {'Statistical Irreproducibility' Does Not Improve with Larger Sample Size: How to Quantify and Address Disease Data Multimodality in Human and Animal Research.}, journal = {Journal of personalized medicine}, volume = {11}, number = {3}, pages = {}, pmid = {33806843}, issn = {2075-4426}, support = {P30 DK097948/DK/NIDDK NIH HHS/United States ; DK118373/NH/NIH HHS/United States ; F32DK117585/NH/NIH HHS/United States ; P01DK091222/NH/NIH HHS/United States ; T32DK083251/NH/NIH HHS/United States ; P30DK097948/NH/NIH HHS/United States ; }, abstract = {Poor study reproducibility is a concern in translational research. As a solution, it is recommended to increase sample size (N), i.e., add more subjects to experiments. The goal of this study was to examine/visualize data multimodality (data with >1 data peak/mode) as cause of study irreproducibility. To emulate the repetition of studies and random sampling of study subjects, we first used various simulation methods of random number generation based on preclinical published disease outcome data from human gut microbiota-transplantation rodent studies (e.g., intestinal inflammation and univariate/continuous). We first used unimodal distributions (one-mode, Gaussian, and binomial) to generate random numbers. We showed that increasing N does not reproducibly identify statistical differences when group comparisons are repeatedly simulated. We then used multimodal distributions (>1-modes and Markov chain Monte Carlo methods of random sampling) to simulate similar multimodal datasets A and B (t-test-p = 0.95; N = 100,000), and confirmed that increasing N does not improve the 'reproducibility of statistical results or direction of the effects'. Data visualization with violin plots of categorical random data simulations with five-integer categories/five-groups illustrated how multimodality leads to irreproducibility. Re-analysis of data from a human clinical trial that used maltodextrin as dietary placebo illustrated multimodal responses between human groups, and after placebo consumption. In conclusion, increasing N does not necessarily ensure reproducible statistical findings across repeated simulations due to randomness and multimodality. Herein, we clarify how to quantify, visualize and address disease data multimodality in research. Data visualization could facilitate study designs focused on disease subtypes/modes to help understand person-person differences and personalized medicine.}, }
@article {pmid33805552, year = {2021}, author = {Pham, VT and Calatayud, M and Rotsaert, C and Seifert, N and Richard, N and Van den Abbeele, P and Marzorati, M and Steinert, RE}, title = {Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro.}, journal = {Nutrients}, volume = {13}, number = {4}, pages = {}, pmid = {33805552}, issn = {2072-6643}, mesh = {Adult ; Antioxidants/*pharmacology ; Bacteria/classification/drug effects ; Caco-2 Cells ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Glucuronates/*pharmacology ; HT29 Cells ; Humans ; Intestinal Mucosa/drug effects/microbiology ; Male ; Oligosaccharides/*pharmacology ; Oxidation-Reduction ; *Prebiotics ; Vitamins/*pharmacology ; }, abstract = {Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.}, }
@article {pmid33804928, year = {2021}, author = {Schmidt, EKA and Raposo, PJF and Madsen, KL and Fenrich, KK and Kabarchuk, G and Fouad, K}, title = {What Makes a Successful Donor? Fecal Transplant from Anxious-Like Rats Does Not Prevent Spinal Cord Injury-Induced Dysbiosis.}, journal = {Biology}, volume = {10}, number = {4}, pages = {}, pmid = {33804928}, issn = {2079-7737}, support = {542589//Craig H. Neilsen Foundation/ ; }, abstract = {Spinal cord injury (SCI) causes gut dysbiosis and an increased prevalence of depression and anxiety. Previous research showed a link between these two consequences of SCI by using a fecal transplant from healthy rats which prevented both SCI-induced microbiota changes and the subsequent development of anxiety-like behaviour. However, whether the physical and mental state of the donor are important factors in the efficacy of FMT therapy after SCI remains unknown. In the present study, rats received a fecal transplant following SCI from uninjured donors with increased baseline levels of anxiety-like behaviour and reduced proportion of Lactobacillus in their stool. This fecal transplant increased intestinal permeability, induced anxiety-like behaviour, and resulted in minor but long-term alterations in the inflammatory state of the recipients compared to vehicle controls. There was no significant effect of the fecal transplant on motor recovery in rehabilitative training, suggesting that anxiety-like behaviour did not affect the motivation to participate in rehabilitative therapy. The results of this study emphasize the importance of considering both the microbiota composition and the mental state of the donor for fecal transplants following spinal cord injury.}, }
@article {pmid33804806, year = {2021}, author = {Jerkic, M and Litvack, ML and Gagnon, S and Otulakowski, G and Zhang, H and Rotstein, O and Kavanagh, BP and Post, M and Laffey, JG}, title = {Embryonic-Derived Myb[-] Macrophages Enhance Bacterial Clearance and Improve Survival in Rat Sepsis.}, journal = {International journal of molecular sciences}, volume = {22}, number = {6}, pages = {}, pmid = {33804806}, issn = {1422-0067}, support = {CIHR Operating Grant #312714/CAPMC/CIHR/Canada ; Foundation Grant FND143309/CAPMC/CIHR/Canada ; }, mesh = {Animals ; *Bacterial Load ; Cytokines/metabolism ; Disease Models, Animal ; Leukocyte Count ; Macrophages/*immunology/*metabolism ; Macrophages, Peritoneal/immunology/metabolism ; Neutrophils/immunology/metabolism ; Phagocytosis/immunology ; Prognosis ; Proto-Oncogene Proteins c-myb/*deficiency ; Rats ; Sepsis/diagnosis/*etiology/*metabolism/mortality ; Severity of Illness Index ; }, abstract = {Peritoneal resident macrophages play a key role in combating sepsis in the peritoneal cavity. We sought to determine if peritoneal transplantation of embryonic Myb[-] "peritoneal-like" macrophages attenuate abdominal fecal sepsis. Directed differentiation of rodent pluripotent stem cells (PSCs) was used in factor-defined media to produce embryonic-derived large "peritoneal-like" macrophages (Ed-LPM) that expressed peritoneal macrophage markers and demonstrated phagocytic capacity. Preclinical in vivo studies determined Ed-LPM efficacy in rodent abdominal fecal sepsis with or without Meropenem. Ex vivo studies explored the mechanism and effects of Ed-LPM on host immune cell number and function, including phagocytosis, reactive oxygen species (ROS) production, efferocytosis and apoptosis. Ed-LPM reduced sepsis severity by decreasing bacterial load in the liver, spleen and lungs. Ed-LPM therapy significantly improved animal survival by ~30% and reduced systemic bacterial burden to levels comparable to Meropenem therapy. Ed-LPM therapy decreased peritoneal TNFα while increasing IL-10 concentrations. Ed-LPMs enhanced peritoneal macrophage phagocytosis of bacteria, increased macrophage production of ROS and restored homeostasis via apoptosis and efferocytosis-induced clearance of neutrophils. In conclusion, Ed-LPM reduced systemic sepsis severity, improved survival and reduced bacterial load by enhancing peritoneal macrophage bacterial phagocytosis and killing and clearance of intra-peritoneal neutrophils. Macrophage therapy may be a potential strategy to address sepsis.}, }
@article {pmid33804464, year = {2021}, author = {Mocanu, V and Rajaruban, S and Dang, J and Kung, JY and Deehan, EC and Madsen, KL}, title = {Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {10}, number = {5}, pages = {}, pmid = {33804464}, issn = {2077-0383}, abstract = {The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the recipient microbiota following FMT. The purpose of our study was to evaluate the effects of two distinct microbial strategies-antibiotic pre-treatment and repeated FMT dosing-on IBD outcomes. A systematic literature review was designed and implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A medical librarian conducted comprehensive searches in MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library on 25 November 2019 and updated on 29 January 2021. Primary outcomes of interest included comparing relapse and remission rates in patients with IBD for a single FMT dose, repeated FMT dosages, and antibiotic pre-treatment groups. Twenty-eight articles (six randomized trials, 20 cohort trials, two case series) containing 976 patients were identified. Meta-analysis revealed that both repeated FMT and antibiotic pre-treatment strategies demonstrated improvements in pooled response and remission rates. These clinical improvements were associated with increases in fecal microbiota richness and α-diversity, as well as the enrichment of several short-chain fatty acid (SCFA)-producing anaerobes including Bifidobacterium, Roseburia, Lachnospiraceae, Prevotella, Ruminococcus, and Clostridium related species.}, }
@article {pmid33804226, year = {2021}, author = {Lorente-Picón, M and Laguna, A}, title = {New Avenues for Parkinson's Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota.}, journal = {Biomolecules}, volume = {11}, number = {3}, pages = {}, pmid = {33804226}, issn = {2218-273X}, support = {LCF/BQ/PR19/11700005//La Caixa Banking Foundation/ ; }, mesh = {Brain/pathology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Humans ; Neuroprotective Agents/pharmacology/therapeutic use ; Parkinson Disease/*drug therapy/*microbiology ; Phylogeny ; }, abstract = {Parkinson's disease (PD) is a multifactorial neurodegenerative disorder that currently affects 1% of the population over the age of 60 years, and for which no disease-modifying treatments exist. Neurodegeneration and neuropathology in different brain areas are manifested as both motor and non-motor symptoms in patients. Recent interest in the gut-brain axis has led to increasing research into the gut microbiota changes in PD patients and their impact on disease pathophysiology. As evidence is piling up on the effects of gut microbiota in disease development and progression, another front of action has opened up in relation to the potential usage of microbiota-based therapeutic strategies in treating gastrointestinal alterations and possibly also motor symptoms in PD. This review provides status on the different strategies that are in the front line (i.e., antibiotics; probiotics; prebiotics; synbiotics; dietary interventions; fecal microbiota transplantation, live biotherapeutic products), and discusses the opportunities and challenges the field of microbiome research in PD is facing.}, }
@article {pmid33800841, year = {2021}, author = {Ooijevaar, RE and van Nood, E and Goorhuis, A and Terveer, EM and van Prehn, J and Verspaget, HW and van Beurden, YH and Dijkgraaf, MGW and Keller, JJ}, title = {Ten-Year Follow-Up of Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection from a Randomized Controlled Trial and Review of the Literature.}, journal = {Microorganisms}, volume = {9}, number = {3}, pages = {}, pmid = {33800841}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) has become a well-established treatment for recurrent Clostridioides difficile infection (rCDI). While short-term outcomes and adverse events relating to FMT have been well documented, there still is a paucity of data with regard to long-term safety. In this report, we describe the long-term follow-up of the prospective cohort of the first randomized controlled trial of FMT for rCDI, and review the existing literature. A total of 34 patients were treated with FMT for rCDI. Seven patients were still alive after a follow-up of more than 10 years and three patients were lost to follow-up. None of the 34 patients had experienced a new-onset autoimmune, gastrointestinal, or malignant disorder during follow-up. We did not find any deterioration or amelioration of pre-existing medical conditions. Furthermore, no deaths directly attributable to FMT could be identified. These findings are in accordance with the data in available literature. In conclusion, no long-term adverse events or complications directly attributable to FMT were found in our prospective cohort. Review of the available literature does not point to long-term risks associated with FMT in this elderly population, provided that carefully screened fecal suspensions are being used. No firm conclusion on the long-term safety of FMT in younger patients could be drawn.}, }
@article {pmid33798737, year = {2021}, author = {Li, X and Khan, I and Xia, W and Huang, G and Liu, L and Law, BYK and Yin, L and Liao, W and Leong, W and Han, R and Wong, VKW and Xia, C and Guo, X and Hsiao, WLW}, title = {Icariin enhances youth-like features by attenuating the declined gut microbiota in the aged mice.}, journal = {Pharmacological research}, volume = {168}, number = {}, pages = {105587}, doi = {10.1016/j.phrs.2021.105587}, pmid = {33798737}, issn = {1096-1186}, mesh = {Aging/*drug effects ; Animals ; Fecal Microbiota Transplantation ; Flavonoids/*pharmacology ; Gastrointestinal Microbiome/*drug effects/physiology ; Goblet Cells/drug effects ; Intestines/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Tight Junctions/drug effects ; }, abstract = {We previously reported the neuroprotective effects of icariin in rat cortical neurons. Here, we present a study on icariin's anti-aging effect in 24-month aged mice by treating them with a single daily dose of 100 mg/kg of icariin for 15 consecutive days. Icariin treatment improved motor coordination and learning skills while lowered oxidative stress biomarkers in the serum, brain, kidney, and liver of the aged mice. In addition, icariin improved the intestinal integrity of the aged mice by upregulating tight junction adhesion molecules and the Paneth and goblet cells, along with the reduction of iNOS and pro-inflammatory cytokines (IL-1β, TNF-α, IL-2 and IL-6, and IL-12). Icariin treatments also significantly upregulated aging-related signaling molecules, Sirt 1, 3 &amp; 6, Pot1α, BUB1b, FOXO1, Ep300, ANXA3, Calb1, SNAP25, and BDNF in old mice. Through gut microbiota (GM) analysis, we observed icariin-associated improvements in GM composition of aged mice by reinstating bacteria found in the young mice, while suppressing some bacteria found in the untreated old mice. To clarify whether icariin's anti-aging effect is rooted in the GM, we performed fecal microbiota transfer (FMT) from icariin-treated old mice to the old mice. FMT-recipients exhibited similar improvements in the rotarod score and age-related biomarkers as observed in the icariin-treated old mice. Equal or better improvement on the youth-like features was noticed when aged mice were FMT with feces from young mice. Our study shows that both direct treatments with icariin and fecal transplant from the icariin-treated aged mice produce similar anti-aging phenotypes in the aged mice. We prove that GM plays a pivotal role in the healing abilities of icariin. Icariin has the potentials to be developed as a medicine for the wellness of the aged adults.}, }
@article {pmid33796545, year = {2021}, author = {Burchill, E and Lymberopoulos, E and Menozzi, E and Budhdeo, S and McIlroy, JR and Macnaughtan, J and Sharma, N}, title = {The Unique Impact of COVID-19 on Human Gut Microbiome Research.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {652464}, pmid = {33796545}, issn = {2296-858X}, abstract = {The coronavirus (COVID-19) pandemic has disrupted clinical trials globally, with unique implications for research into the human gut microbiome. In this mini-review, we explore the direct and indirect influences of the pandemic on the gut microbiome and how these can affect research and clinical trials. We explore the direct bidirectional relationships between the COVID-19 virus and the gut and lung microbiomes. We then consider the significant indirect effects of the pandemic, such as repeated lockdowns, increased hand hygiene, and changes to mood and diet, that could all lead to longstanding changes to the gut microbiome at an individual and a population level. Together, these changes may affect long term microbiome research, both in observational as well as in population studies, requiring urgent attention. Finally, we explore the unique implications for clinical trials using faecal microbiota transplants (FMT), which are increasingly investigated as potential treatments for a range of diseases. The pandemic introduces new barriers to participation in trials, while the direct and indirect effects laid out above can present a confounding factor. This affects recruitment and sample size, as well as study design and statistical analyses. Therefore, the potential impact of the pandemic on gut microbiome research is significant and needs to be specifically addressed by the research community and funders.}, }
@article {pmid33796102, year = {2021}, author = {Chen, H and Shen, L and Liu, Y and Ma, X and Long, L and Ma, X and Ma, L and Chen, Z and Lin, X and Si, L and Chen, X}, title = {Strength Exercise Confers Protection in Central Nervous System Autoimmunity by Altering the Gut Microbiota.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {628629}, pmid = {33796102}, issn = {1664-3224}, mesh = {Animals ; *Autoimmunity ; Bacteria/immunology/*metabolism ; Central Nervous System/*immunology ; Dysbiosis ; Encephalomyelitis, Autoimmune, Experimental/immunology/microbiology/*prevention &amp; control ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Intestine, Small/immunology/*microbiology ; Mice, Inbred C57BL ; Neuroimmunomodulation ; *Physical Conditioning, Animal ; *Resistance Training ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; Mice ; }, abstract = {Exercise therapy including endurance training and resistance training is a promising non-pharmacological therapy in patients with multiple sclerosis (MS). Recent studies have revealed that exercise exerts beneficial impacts on gut microbiota. However, the role of gut microbiota in the immune benefits of strength exercise (SE; one of resistance training) in central nervous system (CNS) autoimmunity is barely known. Here, we observed that 60-min SE ameliorated disease severity and neuropathology in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. SE increased the abundance and diversity of the gut microbiota, and decreased Firmicutes/Bacteroidetes ratio (F/B ratio) and intestinal mucosal permeability, and enrichment of several short-chain fatty acid (SCFA)-producing bacteria. Furthermore, SE reduced Th17 responses and increased Treg responses in the small intestine lymphoid tissues. Compared to the control group, microbiota-depleted mice receiving SE microbiome fecal transplants had lower disease severity and neuropathology scores. These results uncovered a protective role of SE in neuroimmunomodulation effects partly via changes to the gut microbiome.}, }
@article {pmid33795620, year = {2021}, author = {Leung, J and Pham, S}, title = {A Systematic Review of Fecal Microbiota Transplantation Versus Vancomycin for Treatment of Recurrent Clostridioides difficile Infection.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {44}, number = {2}, pages = {106-115}, doi = {10.1097/SGA.0000000000000529}, pmid = {33795620}, issn = {1538-9766}, mesh = {Adult ; Clostridioides ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; *Vancomycin/therapeutic use ; }, abstract = {Clostridioides difficile infection is a major clinical challenge, which may be associated with severe complications. Clostridioides difficile infection may result in repeated episodes of diarrhea, abdominal pain, and dehydration, leading to an increased risk of mortality. Increasingly high rates of recurrent Clostridioides difficile-associated diarrhea, refractory to antibiotic therapy, are difficult to treat. The suboptimal response to antibiotic therapy has led to the need for fecal microbiota transplantation in addition to the more commonly prescribed antibiotic, vancomycin. This systematic review aims to evaluate the effectiveness of fecal microbiota transplantation in the resolution of recurrent Clostridioides difficile infection in adults, compared with an oral vancomycin regimen alone. A systematic literature search was performed, resulting in three randomized control studies. Results from the studies are conflicting, with different variations of study outcomes. In two of the three randomized control trials, fecal microbiota transplantation was statistically significant in effectively resolving Clostridioides difficile infection, but not significant in the third. Although fecal microbiota transplantation results are promising, there are many different variables within the studies, and further research is recommended to explore the effects of these variables within larger sample sizes.}, }
@article {pmid33795522, year = {2021}, author = {Wang, H and Ren, S and Lv, H and Cao, L}, title = {Gut microbiota from mice with cerebral ischemia-reperfusion injury affects the brain in healthy mice.}, journal = {Aging}, volume = {13}, number = {7}, pages = {10058-10074}, pmid = {33795522}, issn = {1945-4589}, mesh = {Animals ; Anxiety/metabolism ; Behavior, Animal/physiology ; Brain/*metabolism ; Brain Ischemia/*metabolism ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Male ; Memory/physiology ; Metagenome ; Mice ; Neuronal Plasticity/physiology ; Reperfusion Injury ; }, abstract = {Gut microorganisms can profoundly influence brain function in the host and their behavior. Since altered brain functional connectivity (FC) has been implicated in various cerebrovascular disorders, including cerebral ischemia-reperfusion (I/R) injury, we hypothesized that gut microbiota in mice with cerebral I/R injury would affect brain FC when transplanted into germ-free mice. Metagenomic analysis of germ-free male C57BL/6J mice colonized with microbiota from mice with and without cerebral I/R injury showed a clear distinction in microbiota composition between mice colonized with control and I/R microbiota. The I/R microbiota-colonized mice showed decreased FC in the cingulate cortex, hippocampus, and thalamus, and exhibited increased anxiety as well as diminished spatial learning and memory and short-term object recognition memory. I/R microbiota-colonized mice also had significantly reduced dendritic spine density and synaptic protein levels and exhibited increased hippocampal inflammation. These results indicate that gut microbiota components from mice with cerebral I/R injury can alter animal behavior, brain functional connectivity, hippocampal neuronal plasticity, and neuroinflammation. Moreover, they increase our understanding of the mechanisms through which the gut microbiome contributes to the pathobiology of cerebrovascular diseases.}, }
@article {pmid33794724, year = {2021}, author = {Manrique, P and Zhu, Y and van der Oost, J and Herrema, H and Nieuwdorp, M and de Vos, WM and Young, M}, title = {Gut bacteriophage dynamics during fecal microbial transplantation in subjects with metabolic syndrome.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-15}, pmid = {33794724}, issn = {1949-0984}, support = {R01 GM117361/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/*virology ; *Bacteriophages ; Biodiversity ; Fecal Microbiota Transplantation/*methods ; Feces/virology ; *Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Male ; Metabolic Syndrome/*microbiology/*therapy ; Middle Aged ; Pilot Projects ; Young Adult ; }, abstract = {Metabolic Syndrome (MetS) is a growing public health concern worldwide. Individuals with MetS have an increased risk for cardiovascular (CV) disease and type 2 diabetes (T2D). These diseases - in part preventable with the treatment of MetS - increase the chances of premature death and pose a great economic burden to health systems. A healthy gut microbiota is associated with a reduction in MetS, T2D, and CV disease. Treatment of MetS with fecal microbiota transplantation (FMT) can be effective, however, its success rate is intermediate and difficult to predict. Because bacteriophages significantly affect the microbiota membership and function, the aim of this pilot study was to explore the dynamics of the gut bacteriophage community after FMT in MetS subjects. We performed a longitudinal study of stool bacteriophages from healthy donors and MetS subjects before and after FMT treatment. Subjects were assigned to either a control group (self-stool transplant, n = 3) or a treatment group (healthy-donor-stool transplant; n-recipients = 6, n-donors = 5). Stool samples were collected over an 18-week period and bacteriophage-like particles were purified and sequenced. We found that FMT from healthy donors significantly alters the gut bacteriophage community. Subjects with better clinical outcome clustered closer to the heathy donor group, suggesting that throughout the treatment, their bacteriophage community was more similar to healthy donors. Finally, we identified bacteriophage groups that could explain these differences and we examined their prevalence in individuals from a larger cohort of MetS FMT trial.Trial information- http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2705; NTR 2705.}, }
@article {pmid33793160, year = {2023}, author = {Qian, Q and He, W and Tang, R and Ma, X}, title = {Implications of gut microbiota in autoimmune liver diseases.}, journal = {Minerva gastroenterology}, volume = {69}, number = {1}, pages = {95-106}, doi = {10.23736/S2724-5985.21.02860-9}, pmid = {33793160}, issn = {2724-5365}, mesh = {Humans ; *Liver Cirrhosis, Biliary/diagnosis/genetics ; *Gastrointestinal Microbiome ; *Cholangitis, Sclerosing/diagnosis/therapy ; *Liver Diseases/etiology ; *Hepatitis, Autoimmune/diagnosis/therapy ; }, abstract = {Autoimmune liver diseases (AILD) are a group of immune-mediated liver inflammatory diseases with three major forms including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Interaction of both genetic and environmental factors leads to the breakdown of self-tolerance, hence resulting in hyper-responsive of autoantibodies and aggressive autoreactive immune cells. Genetic studies have identified dozens of risk loci associated with initiation and development of AILD. However, the role of exogenous factors remains unclear. Recently, both infectious and inflammatory diseases have been associated with microbiota, which colonizes multiple mucosal surfaces and participates in human physiological process and function in immune system, particularly influencing liver, and biliary system via gut-liver axis. Emerging evidence on the role of gut microbiota has expanded our knowledge of AILD in both pathogenesis and potential therapeutic targets, along with putative diagnosis biomarkers. Herein we review the relationship between host and gut microbiota, discuss their potential roles in disease onset and progression, and summarize the compositional and functional alterations of the microbiota in AILD. We also highlighted the microbiota-based therapeutics such as antibiotics and fecal microbiota transplantation (FMT).}, }
@article {pmid33789964, year = {2021}, author = {Parvathy, SN and Lenehan, JG and Fernandes, R and Poutanen, SM and Hota, S and Maleki Vareki, S and Silverman, M}, title = {Enhanced donor screening for faecal microbial transplantation during COVID-19.}, journal = {Gut}, volume = {70}, number = {11}, pages = {2219-2220}, pmid = {33789964}, issn = {1468-3288}, mesh = {*COVID-19 ; *Clostridioides difficile ; Donor Selection ; Fecal Microbiota Transplantation ; Humans ; SARS-CoV-2 ; }, }
@article {pmid33785557, year = {2022}, author = {Ng, SC and Xu, Z and Mak, JWY and Yang, K and Liu, Q and Zuo, T and Tang, W and Lau, L and Lui, RN and Wong, SH and Tse, YK and Li, AYL and Cheung, K and Ching, JYL and Wong, VWS and Kong, APS and Ma, RCW and Chow, EYK and Wong, SKH and Ho, ICH and Chan, PKS and Chan, FKL}, title = {Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: a 24-week, double-blind, randomised controlled trial.}, journal = {Gut}, volume = {71}, number = {4}, pages = {716-723}, doi = {10.1136/gutjnl-2020-323617}, pmid = {33785557}, issn = {1468-3288}, mesh = {*Diabetes Mellitus, Type 2/complications/therapy ; Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Obesity/complications/microbiology/therapy ; Treatment Outcome ; }, abstract = {OBJECTIVE: The impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).<br><br>DESIGN: In this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring &#x2265;20% of microbiota from lean donors at week 24.<br><br>RESULTS: Proportions of subjects acquiring &#x2265;20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in Bifidobacterium and Lactobacillus compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05).<br><br>CONCLUSION: Repeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients' microbiota and improvement in lipid profile and liver stiffness.<br><br>TRIAL REGISTRATION NUMBER: NCT03127696.}, }
@article {pmid33785319, year = {2021}, author = {Bui, TPN and de Vos, WM}, title = {Next-generation therapeutic bacteria for treatment of obesity, diabetes, and other endocrine diseases.}, journal = {Best practice &amp; research. Clinical endocrinology &amp; metabolism}, volume = {35}, number = {3}, pages = {101504}, doi = {10.1016/j.beem.2021.101504}, pmid = {33785319}, issn = {1878-1594}, mesh = {Bacteria ; *Diabetes Mellitus/therapy ; Diet ; *Gastrointestinal Microbiome ; Humans ; Obesity/therapy ; }, abstract = {The human gut microbiota has appeared as an important factor affecting host health and intestinal bacteria have recently emerged as potential therapeutics to treat diabetes and other endocrine diseases. These mainly anaerobic bacteria have been identified either via comparative "omics" analysis of the intestinal microbiota in healthy and diseased subjects or of data collected by fecal microbiota transplantation studies. Both approaches require advanced and in-depth sequencing technologies to perform massive genomic screening to select bacteria with potential benefits. It has been shown that these potentially therapeutic bacteria can either produce bioactive products that directly influence the host patho-physiology and endocrine systems or produce specific signaling molecules that may do so. These bioactive compounds can be formed via degradation of dietary or host-derived components or the conversion of intermediate compounds produced by fermentation of intestinal bacteria. Several of these bacteria have shown causality in preclinical models and entered clinical phase studies, while their mode of action is being analyzed. In this review, we summarize the research on the most promising bacterial candidates with therapeutic properties with a specific focus on diabetes.}, }
@article {pmid33783420, year = {2021}, author = {Sartelli, M and Ansaloni, L and Biffl, WA and Coccolini, F and De Simone, B and Leppaniemi, A and Kluger, Y and Tolonen, M and Moore, EE and Catena, F}, title = {World Society of Emergency Surgery-American Association for the Surgery of Trauma Guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients: An executive summary.}, journal = {The journal of trauma and acute care surgery}, volume = {91}, number = {2}, pages = {422-426}, doi = {10.1097/TA.0000000000003196}, pmid = {33783420}, issn = {2163-0763}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/diagnosis/*therapy ; Enterocolitis, Pseudomembranous/etiology/prevention &amp; control ; Fecal Microbiota Transplantation/methods/trends ; Humans ; Incidence ; Infection Control/methods/trends ; Postoperative Complications/*therapy ; *Practice Guidelines as Topic ; Risk Factors ; Societies, Medical ; }, abstract = {In the last three decades, the dramatic worldwide increase in incidence and severity of Clostridioides difficile infection (CDI) (formerly Clostridium difficile infection) has made CDI a global public health challenge. Surgery is a known risk factor for development of CDI yet surgery is also a treatment option in severe cases of CDI. The World Society of Emergency Surgery guidelines for management of CDI in surgical patients were published in 2015. In 2019, the guidelines were revised and updated according to the grading of recommendations assessment, development and evaluation methodology. This executive summary is intended to consolidate knowledge on the management of CDI focusing on aspects that a general and emergency surgeon should know about the prevention and the management of CDI, by providing a practical and concise version of the original guidelines.}, }
@article {pmid33777828, year = {2021}, author = {Li, C and Pi, G and Li, F}, title = {The Role of Intestinal Flora in the Regulation of Bone Homeostasis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {579323}, pmid = {33777828}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; Homeostasis ; Humans ; Intestines ; Prebiotics ; *Probiotics ; }, abstract = {Intestinal flora located within the intestinal tract comprises a large number of cells, which are referred to as the second gene pool of the human body and form a complex symbiotic relationship with the host. The knowledge of the complex interaction between the intestinal flora and various life activities of the host is a novel and rapidly expanding field. Recently, many studies are being conducted on the relationship between the intestinal flora and bone homeostasis and indicate that the intestinal flora can regulate bone homeostasis via the host immune, metabolic, and endocrine systems. What's more, based on several clinical and preclinical pieces of evidence, changing the composition and function of the host intestinal flora through the application of probiotics, prebiotics, and fecal microbiota transplantation is being considered to be a potential novel target for the regulation of bone homeostasis. Here, we searched relevant literature and reviewed the role of the intestinal flora in the regulation of bone homeostasis and its modulating interventions.}, }
@article {pmid33776811, year = {2021}, author = {Qi, Z and Lyu, M and Yang, L and Yuan, H and Cao, Y and Zhai, L and Dang, W and Liu, J and Yang, F and Li, Y}, title = {A Novel and Reliable Rat Model of Autism.}, journal = {Frontiers in psychiatry}, volume = {12}, number = {}, pages = {549810}, pmid = {33776811}, issn = {1664-0640}, abstract = {Background: Autism spectrum disorders (ASD) is a complex neurodevelopmental disorder that lacks an ideal animal model to recapitulate the disease state of ASD. Previous studies have reported that transplanting gut microbiota of ASD patients into pregnant mice is sufficient to promote the changes of autism-like behavior in offspring. This study aims to explore whether fecal microbiota transplantation (FMT) can be used as a new method to establish the ASD animal model. Methods: We transplanted the fecal sample extract of ASD children into pregnant rats (rFMT) repeatedly to establish an ASD rat model (oFMT) and compare it with the classical valproic acid (VPA) model (oVPA). Results: First, we reveal that oFMT shows hypoevolutism and typical behavioral characteristics of ASD, consistent with the previous study. Second, the gut microbiota of oFMT mainly consists of Firmicutes and Bacteroidetes, recapitulating the abnormal gut microbiota of ASD. In oFMT, the abundance of Lactobacillus and Collinsella increased (Lactobacillus: oFMT 60.16%, oVPA 64.13%, oCON 40.11%; Collinsella: oFMT 3.73%, oVPA 1.39%, oCON 1.28%), compared with oVPA, gut microbiota also showed high consistency. Third, the expression of 5-hydroxytryptamine (5-HT) in oFMT serum increased, γ-aminobutyric acid (GABA) and norepinephrine (NE) in oFMT serum decreased. Fourth, the gut microbiota of oFMT also has some ASD characteristic gut microbiota not found in oVPA. Fifth, pregnant rat with VPA showed significant immune activation, while those with FMT showed relatively minor immune activation. Limitations: Although the mechanism of establishing FMT autism rat model (oFMT) has not clearly defined, the data show that the model has high structural validity, and FMT model is likely to be a new and reliable potential animal model of ASD, and will have potential value in studying gut microbiota of ASD. Conclusions: The FMT autism rat model has high structural validity, and the FMT model is likely to be a new and reliable potential animal model of ASD.}, }
@article {pmid33775619, year = {2021}, author = {Farhadfar, N and Gharaibeh, RZ and Dahl, WJ and Mead, L and Alabasi, KM and Newsome, R and IrizarryGatell, V and Weaver, MT and Al-Mansour, Z and Jobin, C and Lyon, D and Wingard, JR and Kelly, DL}, title = {Gut Microbiota Dysbiosis Associated with Persistent Fatigue in Hematopoietic Cell Transplantation Survivors.}, journal = {Transplantation and cellular therapy}, volume = {27}, number = {6}, pages = {498.e1-498.e8}, doi = {10.1016/j.jtct.2021.02.017}, pmid = {33775619}, issn = {2666-6367}, mesh = {Adult ; Cross-Sectional Studies ; *Dysbiosis ; *Fatigue ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Quality of Life ; RNA, Ribosomal, 16S ; Survivors ; }, abstract = {Fatigue is one of the most prevalent and distressing complications among hematopoietic stem cell transplantation (HCT) survivors, negatively affecting physical, social, and emotional domains of quality of life. Chronic systemic inflammation has been linked to alterations in nervous system activity and initiation of distressing symptoms, such as fatigue. Damage to gut mucosa due to alteration in gut microbiota (GM) composition and microbial translocation has been shown to increase systemic proinflammatory cytokines. The aim of this study was to evaluate the relationship between fatigue and GM by measuring the differences in GM composition in HCT survivors with and without persistent fatigue. This cross-sectional study included 30 adults who underwent HCT for a hematologic disease and were at least 1 year post-HCT. Patients with chronic graft-versus-host disease were excluded. Fatigue severity was assessed by the Brief Fatigue Inventory (BFI). Based on the BFI score, patients were grouped into 2 categories: 0 to 3 (without fatigue) and ≥4 (with fatigue). The V1 to V3 region of the 16S rRNA gene from fecal specimens was sequenced using the Illumina MiSeq. Sequencing reads were processed, denoised, and replicated, chimeras were filtered, amplicon sequence variants (ASVs) were generated, and taxonomy was assigned using DADA2. Beta diversity analysis through principal coordinate analysis was generated using the Bray-Curtis dissimilarity matrix, and the difference was tested using linear model with generalized least squares in R. An alpha diversity analysis was performed using Chao1. Linear discriminant analysis effect size (LEfSe) was used to find markers that differ between the 2 groups. Based on the BFI results, patients were categorized into 2 cohorts: with fatigue (n = 14) and without fatigue (n = 16). The 2 cohorts were similar in terms of demographics, disease, and transplant characteristics. Based on the GM analysis, there was a significant difference in GM composition (beta diversity) between the 2 cohorts (P = .001). Alpha diversity (richness) was also significantly lower in survivors with fatigue (P =.002). LEfSe analysis identified 46 discriminative features (P < .05; linear discriminant analysis score >2) whose relative abundance varied significantly among individuals with fatigue and those without fatigue. Ten ASVs were associated with the patients with fatigue, and 36 ASVs were associated with those without fatigue. Several ASVs enriched in survivors with fatigue included organisms such as Klebsiella and Enterococcus, which have been implicated in inflammatory bowel diseases. The ASVs enriched in the cohort without fatigue were members of the Ruminococcaceae family (Oscillospira spp) and the Lachnospiraceae family (Fusicatenibacter and Coprococcus spp), which are known to have the ability to ferment complex plant carbohydrates. These findings show an association between GM composition and fatigue and suggest a microbial contribution to clinically significant fatigue post-HCT, which may guide the development of new approaches to treating fatigue based on manipulation of the GM.}, }
@article {pmid33775068, year = {2021}, author = {Karolewska-Bochenek, K and Lazowska-Przeorek, I and Grzesiowski, P and Dziekiewicz, M and Dembinski, L and Albrecht, P and Radzikowski, A and Banaszkiewicz, A}, title = {Faecal Microbiota Transfer - a new concept for treating cytomegalovirus colitis in children with ulcerative colitis.}, journal = {Annals of agricultural and environmental medicine : AAEM}, volume = {28}, number = {1}, pages = {56-60}, doi = {10.26444/aaem/118189}, pmid = {33775068}, issn = {1898-2263}, mesh = {Adolescent ; Child ; Child, Preschool ; Colitis, Ulcerative/microbiology/*therapy/virology ; Colon/microbiology/virology ; Cytomegalovirus/*physiology ; Cytomegalovirus Infections/microbiology/*therapy/virology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Pilot Projects ; Prospective Studies ; }, abstract = {INTRODUCTION: Cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD) is reactivated by the use of immunosuppressive drugs. CMV infection may produce IBD flares refractory to standard therapy.<br><br>OBJECTIVE: The aim of our study was to assess the efficacy and safety of faecal microbiota transplantation (FMT) for the treatment of CMV colitis in patients with ulcerative colitis (UC) flare.<br><br>MATERIAL AND METHODS: A total of 8 children, with mild to severe UC, positive for CMV PCR in colonic biopsies, received 50-100 ml FMT by nasogastric tube on 5 consecutive days in each of 2 weeks. During the study, the subjects were treated with 5ASA and FMT. Immunosuppressant therapy was withdrawn, when CMV colitis was diagnosed by positive DNA PCR in colonic tissues. The clinical response was defined as a decrease of Paediatric UC Activity Index by &#x2265;20 points.<br><br>RESULTS: At the 6th week of the study, negative colonic CMV DNA PCR was measured after 10 infusions in 7/8 patients. For one boy, 20 infusions were administered to assess CMV elimination from colonic biopsies. A clinical response was observed in 3/8 patients, with clinical remission in 3/8 patients. Faecal calprotectin decreased significantly in 3 patients. CRP normalized in 2 patients after 6 weeks. No serious adverse effects were observed during and after infusions.<br><br>CONCLUSIONS: FMT seems to be an effective and safe treatment option for CMV colitis in children with UC. This is the first study to demonstrate the application of FMT as a new therapeutic option for CMV colitis.}, }
@article {pmid33773125, year = {2021}, author = {Zaman, A and Qazi, T and Pai, P and Peters, P and Nicolaysen, S and Olesen, SW}, title = {Carriage rates of multidrug-resistant organisms among prospective stool donors.}, journal = {The Lancet. Infectious diseases}, volume = {21}, number = {4}, pages = {454-455}, doi = {10.1016/S1473-3099(21)00091-8}, pmid = {33773125}, issn = {1474-4457}, mesh = {Carrier State/epidemiology ; *Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Prospective Studies ; Quarantine ; Retrospective Studies ; }, }
@article {pmid33770330, year = {2022}, author = {Ma, C and MacDonald, JK and Nguyen, TM and Vande Casteele, N and Linggi, B and Lefevre, P and Wang, Y and Feagan, BG and Jairath, V}, title = {Pharmacological Interventions for the Prevention and Treatment of Immune Checkpoint Inhibitor-Associated Enterocolitis: A Systematic Review.}, journal = {Digestive diseases and sciences}, volume = {67}, number = {4}, pages = {1128-1155}, pmid = {33770330}, issn = {1573-2568}, mesh = {*Enterocolitis/chemically induced/diagnosis/prevention &amp; control ; Humans ; *Immune Checkpoint Inhibitors/adverse effects ; Immunosuppressive Agents/therapeutic use ; Infliximab/therapeutic use ; Ipilimumab ; }, abstract = {BACKGROUND: Patients treated with immune checkpoint inhibitors (ICIs) may develop ICI-associated enterocolitis, for which there is no approved treatment.<br><br>AIMS: We aimed to systematically review the efficacy and safety of medical interventions for the prevention and treatment of ICI-associated enterocolitis.<br><br>METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials (RCTs), cohort and case-control studies, and case series/reports, evaluating interventions (including corticosteroids, biologics, aminosalicylates, immunosuppressants, and fecal transplantation) for ICI-associated enterocolitis. Clinical, endoscopic, and histologic efficacy endpoints were evaluated. The Grading of Recommendations, Assessment, Development, and Evaluation criteria were used to assess overall quality of evidence.<br><br>RESULTS: A total of 160 studies (n&#x2009;=&#x2009;1514) were included (one RCT, 3 retrospective cohort studies, 156 case reports/case series). Very low quality evidence from one RCT suggests budesonide is not effective for prevention of ICI-associated enterocolitis in ipilimumab-treated patients (relative risk 0.93 [95% confidence interval 0.56, 1.56]). Very low quality evidence suggests that corticosteroids, infliximab, and vedolizumab may be effective for treatment of ICI-associated enterocolitis by inducing clinical response and remission. No validated indices for measuring disease activity were used. Biologic treatment was used in 42% (641/1528) of patients, as reported in 97 studies. ICIs were discontinued in 65% (457/702) of patients, as reported in 63 studies.<br><br>CONCLUSIONS: Current treatment recommendations for ICI-associated enterocolitis are based on very low quality evidence, primarily from case reports and case series. Large-scale prospective cohort studies and RCTs are needed to develop prophylactic and therapeutic treatments to minimize interruption or discontinuation of oncological therapies.}, }
@article {pmid33769374, year = {2021}, author = {German, MN and Musto, J and Lucey, MR}, title = {Novel treatments for alcoholic hepatitis.}, journal = {Current opinion in gastroenterology}, volume = {37}, number = {3}, pages = {179-186}, doi = {10.1097/MOG.0000000000000725}, pmid = {33769374}, issn = {1531-7056}, mesh = {Alcohol Abstinence ; Fecal Microbiota Transplantation ; *Hepatitis, Alcoholic/drug therapy ; Humans ; *Liver Diseases, Alcoholic ; *Liver Transplantation ; }, abstract = {PURPOSE OF REVIEW: The current article aims to review the latest literature on updates in therapeutics for alcohol-associated liver disease (ALD), integration of treatment of alcohol use disorder (AUD) into the management of ALD, and the role of liver transplantation for alcoholic hepatitis.<br><br>RECENT FINDINGS: ALD has recently become the most common indication for liver transplantation due to the increasing prevalence of AUD and the paucity of therapeutic options. There is broad consensus on the importance of early identification of AUD and the incorporation of its treatment in the management of ALD. New targets for treatment of alcoholic hepatitis include the gut-liver axis, anti-inflammatory drugs, antioxidants, and drugs with hepatic regenerative potential. Fecal transplantation in particular has had favorable outcomes at 1 year. n-Acetylcysteine in addition to corticosteroids, granulocyte colony stimulating factor, and IL-22 have also shown improved short-term outcomes. A number of other therapies are being studied in clinical trials and their results are anxiously awaited.<br><br>SUMMARY: In summary, there are several promising therapeutic options under clinical investigation for the treatment of alcoholic hepatitis and ALD; however, alcohol abstinence is key. In the absence of other effective therapies, liver transplantation for ALD remains a life-saving treatment with excellent patient and graft survival.}, }
@article {pmid33769200, year = {2021}, author = {Glenny, EM and Fouladi, F and Thomas, SA and Bulik-Sullivan, EC and Tang, Q and Djukic, Z and Trillo-Ordonez, YS and A Fodor, A and Tarantino, LM and M Bulik, C and M Carroll, I}, title = {Gut microbial communities from patients with anorexia nervosa do not influence body weight in recipient germ-free mice.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-15}, pmid = {33769200}, issn = {1949-0984}, support = {R01 MH119084/MH/NIMH NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; R01 MH105684/MH/NIMH NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 MH118278/MH/NIMH NIH HHS/United States ; R01 MH120170/MH/NIMH NIH HHS/United States ; T32 DK007686/DK/NIDDK NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; U01 MH109528/MH/NIMH NIH HHS/United States ; }, mesh = {Adiposity ; Adult ; Animals ; Anorexia Nervosa/*microbiology ; Bacteria/*growth &amp; development ; *Body Weight ; Cecum/physiology ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Humans ; Male ; Mice ; Organ Size ; }, abstract = {Anorexia nervosa (AN) is a psychiatric disorder that presents with profound weight dysregulation, metabolic disturbances, and an abnormal composition of gut microbial communities. As the intestinal microbiota can influence host metabolism, the impact of enteric microbial communities from patients with AN on host weight and adiposity was investigated. Germ-free (GF) mice were colonized with fecal microbiotas from either patients with AN (n = 4) prior to inpatient treatment (AN T1, n = 50 recipient mice), the same 4 patients following clinical renourishment (AN T2, n = 53 recipient mice), or age- and sex-matched non-AN controls (n = 4 human donors; non-AN, n = 50 recipient mice). Biological and fecal microbiota data were analyzed with linear mixed-effects models. Body weight did not differ significantly between AN recipient mice (T1 and T2) and non-AN recipient mice following 4 weeks of colonization. Enteric microbiotas from recipient mice colonized with AN T1 and AN T2 fecal microbiotas were more similar to each other compared with enteric microbiotas from non-AN recipient mice. Specific bacterial families in the Actinobacteria, Bacteroidetes, and Firmicutes phyla were significantly associated with body weight, fat mass, and cecum weight irrespective of the donor group. These data suggest that body weight, fat mass, and cecum weight of colonized GF mice are associated with human fecal microbes and independent of donor AN status, although additional analyses with larger cohorts are warranted.}, }
@article {pmid33766699, year = {2021}, author = {Munshi, S}, title = {A depressed gut makes for a depressed brain via vagal transmission.}, journal = {Brain, behavior, and immunity}, volume = {95}, number = {}, pages = {15-16}, doi = {10.1016/j.bbi.2021.03.017}, pmid = {33766699}, issn = {1090-2139}, mesh = {Animals ; Brain ; *Depression ; *Fecal Microbiota Transplantation ; Mice ; Mice, Knockout ; Phenotype ; Vagus Nerve ; alpha7 Nicotinic Acetylcholine Receptor ; }, }
@article {pmid33765728, year = {2021}, author = {Moon, CM and Hong, SN}, title = {Fecal Microbiota Transplantation beyond Clostridioides Difficile Infection.}, journal = {Clinical endoscopy}, volume = {54}, number = {2}, pages = {149-151}, pmid = {33765728}, issn = {2234-2400}, abstract = {With advancing analytical methods for gut microbes, many studies have been conducted, revealing that gut microbes cause various diseases, including gastrointestinal and non-gastrointestinal diseases. Accordingly, studies have been actively conducted to analyze the effects on the prevention and treatment of these diseases through changes in intestinal microbes and control of dysbiosis. Fecal microbiota transplantation (FMT) is an effort and is currently being applied to Clostridioides difficile treatment in Korea. Many studies have demonstrated the application of FMT in inflammatory bowel disease, irritable bowel syndrome, non-alcoholic fatty liver disease, metabolic syndrome, obesity, and diabetes. With further studies and accumulation of evidence, FMT could help treat presently untreatable diseases in clinical practice.}, }
@article {pmid33763383, year = {2021}, author = {Chen, ZJ and Liang, CY and Yang, LQ and Ren, SM and Xia, YM and Cui, L and Li, XF and Gao, BL}, title = {Association of Parkinson's Disease With Microbes and Microbiological Therapy.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {619354}, pmid = {33763383}, issn = {2235-2988}, mesh = {Catechol O-Methyltransferase ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Levodopa ; *Parkinson Disease/drug therapy ; }, abstract = {Parkinson's disease (PD) is the most common movement disorder in the world, affecting 1-2 per 1,000 of the population. The main pathological changes of PD are damage of dopaminergic neurons in substantia nigra of the central nervous system and formation of Lewy bodies. These pathological changes also occur in the intestinal tract and are strongly associated with changes in intestinal flora. By reviewing the research progress in PD and its association with intestinal flora in recent years, this review expounded the mechanism of action between intestinal flora and PD as well as the transmission mode of α - synuclein in neurons. In clinical studies, β diversity of intestinal flora in PD patients was found to change significantly, with Lactobacillusaceae and Verrucomicrobiaceae being significantly increased and Lachnospiraceae and Prevotellaceae being significantly decreased. In addition, a longer PD course was associated with fewer bacteria and probiotics producing short chain fatty acids, but more pathogenic bacteria. Moreover, the motor symptoms of PD patients may be related to Enterobacteriaceae and bacteria. Most importantly, catechol-O-methyltransferase inhibitors and anticholinergic drugs could change the intestinal flora of PD patients and increase the harmful flora, whereas other anti-PD drugs such as levodopa, dopamine agonist, monoamine oxidase inhibitors, and amantadine did not have these effects. Probiotics, prebiotics, and synbiotics treatment had some potential values in improving the constipation of PD patients, promoting the growth of probiotics, and improving the level of intestinal inflammation. At present, there were only a few case studies and small sample studies which have found certain clinical efficacy of fecal microbiome transplants. Further studies are necessary to elaborate the relationship of PD with microbes.}, }
@article {pmid33762166, year = {2021}, author = {Mejía-Granados, DM and Villasana-Salazar, B and Lozano-García, L and Cavalheiro, EA and Striano, P}, title = {Gut-microbiota-directed strategies to treat epilepsy: clinical and experimental evidence.}, journal = {Seizure}, volume = {90}, number = {}, pages = {80-92}, doi = {10.1016/j.seizure.2021.03.009}, pmid = {33762166}, issn = {1532-2688}, mesh = {Animals ; Brain ; *Epilepsy/therapy ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {A growing appreciation that the intestinal microbiota might exert changes on the central nervous system via the gut-brain has emerged as a new research frontier in neurological disorders. Moreover, new approaches for studying and manipulating the gut microbiome, including metabolomics and faecal microbiota transplantation, have highlighted the tremendous potential that microbes have on neuroinflammation, metabolic, and neuroendocrine signaling pathways. Despite the large proliferation of studies in animal models examining the linkage between microbial disequilibrium and epilepsy, intestinal profiles at a functional level in humans have remained scarce. We reviewed the scientific evidence on gut microbiota's role in epilepsy, both in clinical and experimental studies, to better understand how targeting the gut microbiota could serve as a diagnostic or prognostic research tool. Likewise, translating microbial molecular mechanisms to medical settings could fill the gaps related to alternative therapies for patients with epilepsy, mainly in cases with refractory phenotypes.}, }
@article {pmid33761228, year = {2021}, author = {Gweon, TG and Na, SY}, title = {Next Generation Fecal Microbiota Transplantation.}, journal = {Clinical endoscopy}, volume = {54}, number = {2}, pages = {152-156}, pmid = {33761228}, issn = {2234-2400}, abstract = {Fecal microbiota transplantation (FMT) is considered as an effective treatment for Clostridioides difficile infection. However, the precise mechanism of FMT is yet to be determined. Human stool consists of the gut microbiota, bacterial debris, and metabolic products. Of these, the intestinal microbiota is the most important factor that exerts therapeutic efficacy in FMT. Fresh donor stool, blended with normal saline, has been employed for traditional FMT. Nevertheless, stool processing is a major impediment in FMT. Frozen stool and capsule formulations have similar efficacy to that of fresh stool. In addition, several novel stool products have been identified. A stool bank that provides stool products with pre-screened donor stool has been established to help physicians and thereby facilitate FMT. Recent next-generation sequencing techniques have been key in facilitating the detailed analysis of the microbiota and gut environment of individual donors and recipients.}, }
@article {pmid33759066, year = {2021}, author = {Cheng, F and Huang, Z and Wei, W and Li, Z}, title = {Fecal microbiota transplantation for Crohn's disease: a systematic review and meta-analysis.}, journal = {Techniques in coloproctology}, volume = {25}, number = {5}, pages = {495-504}, pmid = {33759066}, issn = {1128-045X}, mesh = {*Crohn Disease/therapy ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Inflammatory Bowel Diseases ; Intestines ; Treatment Outcome ; }, abstract = {BACKGROUND: Crohn's disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbiota transplantation (FMT) is an emerging treatment approach for CD. But its efficacy and safety remain controversial. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD patients.<br><br>METHODS: Electronic databases were searched for studies that reported efficacy and/or safety of FMT for CD. Clinical remission was established as the primary outcome. Secondary outcome was clinical response. Odds ratios with 95% confidence intervals (CIs) were reported.<br><br>RESULTS: In all, 12 trials were included in our study. Pooled analysis showed that 0.62 (95% CI 0.48, 0.81) of CD patients achieved clinical remission and 0.79 (95% CI 0.71, 0.89) of CD patients achieved clinical response post-FMT. Sub-analyses suggested the rate of clinical remission with fresh stool FMT was higher than with frozen stool FMT (73% vs 43%; p&#x2009;<&#x2009;0.05). Most adverse events were minor and self-resolving and no major FMT-related adverse event has been reported so far.<br><br>CONCLUSIONS: The evidence showed that FMT is an effective and safe therapy for CD. FMT may be successful because it increases the overall diversity of enteric microbiome. Additional randomized controlled studies are needed.}, }
@article {pmid33758825, year = {2021}, author = {Dees, KJ and Koo, H and Humphreys, JF and Hakim, JA and Crossman, DK and Crowley, MR and Nabors, LB and Benveniste, EN and Morrow, CD and McFarland, BC}, title = {Human gut microbial communities dictate efficacy of anti-PD-1 therapy in a humanized microbiome mouse model of glioma.}, journal = {Neuro-oncology advances}, volume = {3}, number = {1}, pages = {vdab023}, pmid = {33758825}, issn = {2632-2498}, support = {P30 CA013148/CA/NCI NIH HHS/United States ; R01 CA194414/CA/NCI NIH HHS/United States ; R03 NS116559/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: Although immunotherapy works well in glioblastoma (GBM) preclinical mouse models, the therapy has not demonstrated efficacy in humans. To address this anomaly, we developed a novel humanized microbiome (HuM) model to study the response to immunotherapy in a preclinical mouse model of GBM.<br><br>METHODS: We used 5 healthy human donors for fecal transplantation of gnotobiotic mice. After the transplanted microbiomes stabilized, the mice were bred to generate 5 independent humanized mouse lines (HuM1-HuM5).<br><br>RESULTS: Analysis of shotgun metagenomic sequencing data from fecal samples revealed a unique microbiome with significant differences in diversity and microbial composition among HuM1-HuM5 lines. All HuM mouse lines were susceptible to GBM transplantation, and exhibited similar median survival ranging from 19 to 26 days. Interestingly, we found that HuM lines responded differently to the immune checkpoint inhibitor anti-PD-1. Specifically, we demonstrate that HuM1, HuM4, and HuM5 mice are nonresponders to anti-PD-1, while HuM2 and HuM3 mice are responsive to anti-PD-1 and displayed significantly increased survival compared to isotype controls. Bray-Curtis cluster analysis of the 5 HuM gut microbial communities revealed that responders HuM2 and HuM3 were closely related, and detailed taxonomic comparison analysis revealed that Bacteroides cellulosilyticus was commonly found in HuM2 and HuM3 with high abundances.<br><br>CONCLUSIONS: The results of our study establish the utility of humanized microbiome mice as avatars to delineate features of the host interaction with gut microbial communities needed for effective immunotherapy against GBM.}, }
@article {pmid33758177, year = {2021}, author = {Wang, W and Zhai, D and Bai, Y and Xue, K and Deng, L and Ma, L and Du, T and Ye, Z and Qu, D and Xiang, A and Chen, G and Zhao, Y and Wang, L and Lu, Z}, title = {Loss of QKI in macrophage aggravates inflammatory bowel disease through amplified ROS signaling and microbiota disproportion.}, journal = {Cell death discovery}, volume = {7}, number = {1}, pages = {58}, pmid = {33758177}, issn = {2058-7716}, abstract = {Inflammatory bowel disease (IBD) is a refractory chronic inflammatory illness of the gastrointestinal (GI) tract. Macrophage exerts an important role in IBD development. QKI, as an RNA binding protein, was related with inflammatory responses in bacterial infections by regulating the polarization of macrophages. Therefore, we suspected that QKI-regulated macrophages have the potential to play a certain role in IBD and the underlying mechanism. Our results demonstrated that the mice with macrophage-specific deletion of QKI induced with dextran sodium sulfate (DSS) are more susceptible to IBD development, exhibited a severe leaky gut barrier phenotype and higher intense oxidative stress, which are rescued by treating with butylated hydroxyanisole (BHA), an agonist of NRF2. Mechanically, we observed that Keap1 mRNA in the nucleus was exported to the cytoplasm after LPS stimuli in parallel with QKI reductions, and the removal of QKI by shRNA facilitated Keap1 mRNA nuclear exporting and expression in cytoplasm, consequently NRF2 activation in nucleus was weakened, and led to the impaired antioxidant abilities. In addition, mice models of fecal microbiota transplant (FMT) and the co-culturing of mice epithelia cells with feces derived from the DSS-treated QKI-deficit mice revealed consistently aggravated colitis along with a severe oxidative stress; 16S sequencing analysis substantiated the altered compositions of commensal bacteria too. Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice.}, }
@article {pmid33757553, year = {2021}, author = {Santiago, M and Olesen, SW}, title = {16S rRNA sequencing of samples from universal stool bank donors.}, journal = {BMC research notes}, volume = {14}, number = {1}, pages = {108}, pmid = {33757553}, issn = {1756-0500}, mesh = {*Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; Humans ; RNA, Ribosomal, 16S/genetics ; Tissue Donors ; }, abstract = {OBJECTIVES: Universal stool banks provide stool to physicians for use in treating recurrent Clostridioides difficile infection via fecal microbiota transplantation. Stool donors providing the material are rigorously screened for diseases and disorders with a potential microbiome etiology, and they are likely healthier than the controls in most microbiome datasets. 16S rRNA sequencing was performed on samples from a selection of stool donors at a large stool bank, OpenBiome, to characterize their gut microbial community and to compare samples across different timepoints and sequencing runs.<br><br>DATA DESCRIPTION: 16S rRNA sequencing was performed on 200 samples derived from 170 unique stool donations from 86 unique donors. Samples were sequenced on 11 different sequencing runs. We are making this data available because rigorously screened, likely very healthy stool donors may be useful for characterizing and understanding microbial community differences across different populations and will help shed light into the how the microbiome community promotes health and disease.}, }
@article {pmid33757127, year = {2022}, author = {Zhang, Y and Zhang, S and Li, B and Luo, Y and Gong, Y and Jin, X and Zhang, J and Zhou, Y and Zhuo, X and Wang, Z and Zhao, X and Han, X and Gao, Y and Yu, H and Liang, D and Zhao, S and Sun, D and Wang, D and Xu, W and Qu, G and Bo, W and Li, D and Wu, Y and Li, Y}, title = {Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome.}, journal = {Cardiovascular research}, volume = {118}, number = {3}, pages = {785-797}, doi = {10.1093/cvr/cvab114}, pmid = {33757127}, issn = {1755-3245}, mesh = {Aged ; Animals ; *Atrial Fibrillation ; Cross-Sectional Studies ; Dysbiosis/complications ; *Gastrointestinal Microbiome ; Glucose ; Humans ; Inflammasomes/metabolism ; Lipopolysaccharides ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Rats ; }, abstract = {AIMS: Ageing is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-related diseases. However, whether the aged-associated dysbiosis contributes to age-related AF is still unknown. Direct demonstration that the aged gut microbiota is sufficient to transmit the enhanced AF susceptibility in a young host via microbiota-intestinal barrier-atria axis has not yet been reported. This study aimed to determine whether gut microbiota dysbiosis affects age-related AF.<br><br>METHODS AND RESULTS: Herein, by using a faecal microbiota transplantation (FMT) rat model, we demonstrated that the high AF susceptibility of aged rats could be transmitted to a young host. Specially, we found the dramatically increased levels of circulating lipopolysaccharide (LPS) and glucose led to the up-regulated expression of NOD-like receptor protein (NLRP)-3 inflammasome, promoting the development of AF, which depended on the enhanced atrial fibrosis in recipient host. Inhibition of inflammasome by a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, resulted in a lower atrial fibrosis and AF susceptibility. Then, we conducted cross-sectional clinical studies to explore the effect of ageing on the altering trends with glucose levels and circulating LPS among clinical individuals in two China hospitals. We found that both of serum LPS and glucose levels were progressively increased in elderly patients as compared with those young. Furthermore, the ageing phenotype of circulating LPS and glucose levels, intestinal structure and atrial NLRP3-inflammasome of rats were also confirmed in clinical AF patients. Finally, aged rats colonized with youthful microbiota restored intestinal structure and atrial NLRP3-inflammasome activity, which suppressed the development of aged-related AF.<br><br>CONCLUSIONS: Collectively, these studies described a novel causal role of aberrant gut microbiota in the pathogenesis of age-related AF, which indicates that the microbiota-intestinal barrier-atrial NLRP3 inflammasome axis may be a rational molecular target for the treatment of aged-related arrhythmia disease.}, }
@article {pmid33754054, year = {2021}, author = {Zhang, SL and Mao, YQ and Zhang, ZY and Li, ZM and Kong, CY and Chen, HL and Cai, PR and Han, B and Ye, T and Wang, LS}, title = {Pectin supplement significantly enhanced the anti-PD-1 efficacy in tumor-bearing mice humanized with gut microbiota from patients with colorectal cancer.}, journal = {Theranostics}, volume = {11}, number = {9}, pages = {4155-4170}, pmid = {33754054}, issn = {1838-7640}, mesh = {Aged ; Animals ; Antibodies, Monoclonal/*therapeutic use ; Bacteria ; CD8-Positive T-Lymphocytes/drug effects/metabolism ; Cell Line, Tumor ; Colorectal Neoplasms/*drug therapy/*metabolism ; Fatty Acids, Volatile/metabolism ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Pectins/*administration &amp; dosage ; Programmed Cell Death 1 Receptor/*antagonists &amp; inhibitors ; RNA, Ribosomal, 16S/metabolism ; Tumor Microenvironment/drug effects ; }, abstract = {Background: Anti-PD-1-based immunotherapy has emerged as a promising therapy for several cancers. However, it only benefits a small subset of colorectal cancer (CRC) patients. Mounting data supports the pivotal role of gut microbiota in shaping immune system. Pectin, a widely consumed soluble fiber, has been reported to ameliorate the imbalance of gut microbiota. Therefore, we aimed to explore the effect and the underlying mechanisms of pectin in improving anti-PD-1 mAb efficacy. Methods: The C57BL/6 mice were treated with a broad-spectrum antibiotic (ATB) cocktail to depleted endogenous gut microbiota and subsequently humanized with feces from healthy controls or newly diagnosed CRC patients. The antitumor efficacies of anti-PD-1 mAb combined with or without pectin were assessed using these mice. Flow cytometry and immunohistochemistry (IHC) were conducted to investigate the tumor immune microenvironment after treatment. The gut microbiota profiles and short-chain fatty acids (SCFAs) levels were determined by 16S ribosomal RNA (16S rRNA) gene sequencing and gas chromatography-mass spectrometry (GC-MS), respectively. The effect of gut microbiota on anti-PD-1 mAb efficacy after pectin supplement was further tested by fecal microbiota transplantation (FMT). Results: The anti-PD-1 mAb efficacy was largely impaired in the mice humanized with feces from newly diagnosed CRC patients compared to those from healthy controls. However, pectin significantly enhanced the anti-PD-1 mAb efficacy in the tumor-bearing mice humanized with CRC patient gut microbiota. Flow cytometry and IHC analysis revealed increased T cell infiltration and activation in the tumor microenvironment of mice treated with anti-PD-1 mAb plus pectin. In vivo depletion of CD8[+] T cells diminished the anti-tumor effect of anti-PD-1 mAb combined with pectin. 16S rRNA gene sequencing showed that pectin significantly increased gut microbial diversity and beneficially regulated microbial composition. In addition, we identified unique bacterial modules that were significantly enriched in the anti-PD-1 mAb + pectin group, which composed of butyrate-producing bacteria indicative of good response to immunotherapy. Meanwhile, GC-MS showed that pectin altered the level of SCFA butyrate. Furthermore, butyrate, a main product of dietary fiber in gut microbial fermentation, was found to be sufficient to promote T cells infiltration and thus enhance the efficacy of anti-PD-1 mAb. In addition, FMT demonstrated the effects of pectin were dependent on gut microbiota. Importantly, the beneficial effects of pectin were confirmed in the mice humanized with gut microbiota from patient with resistance to anti-PD-1 mAb. Conclusion: Pectin facilitated the anti-PD-1 mAb efficacy in CRC via regulating the T cell infiltration in the tumor microenvironment, which was potentially mediated by the metabolite butyrate.}, }
@article {pmid33754024, year = {2021}, author = {Lu, J and Chen, PP and Zhang, JX and Li, XQ and Wang, GH and Yuan, BY and Huang, SJ and Liu, XQ and Jiang, TT and Wang, MY and Liu, WT and Ruan, XZ and Liu, BC and Ma, KL}, title = {GPR43 deficiency protects against podocyte insulin resistance in diabetic nephropathy through the restoration of AMPKα activity.}, journal = {Theranostics}, volume = {11}, number = {10}, pages = {4728-4742}, pmid = {33754024}, issn = {1838-7640}, mesh = {AMP-Activated Protein Kinases/*metabolism ; Adult ; Aged ; Animals ; Diabetes Mellitus, Experimental/*metabolism ; Diabetic Nephropathies/*genetics/metabolism ; Dysbiosis/*genetics/metabolism ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Insulin Resistance/*genetics ; Kidney/metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Microscopy, Electron, Transmission ; Middle Aged ; Podocytes/*metabolism ; Rats ; Receptors, Cell Surface/genetics ; Receptors, G-Protein-Coupled/*genetics ; Young Adult ; }, abstract = {Rationale: Albuminuria is an early clinical feature in the progression of diabetic nephropathy (DN). Podocyte insulin resistance is a main cause of podocyte injury, playing crucial roles by contributing to albuminuria in early DN. G protein-coupled receptor 43 (GPR43) is a metabolite sensor modulating the cell signalling pathways to maintain metabolic homeostasis. However, the roles of GPR43 in podocyte insulin resistance and its potential mechanisms in the development of DN are unclear. Methods: The experiments were conducted by using kidney tissues from biopsied DN patients, streptozotocin (STZ) induced diabetic mice with or without global GPR43 gene knockout, diabetic rats treated with broad-spectrum oral antibiotics or fecal microbiota transplantation, and cell culture model of podocytes. Renal pathological injuries were evaluated by periodic acid-schiff staining and transmission electron microscopy. The expression of GPR43 with other podocyte insulin resistance related molecules was checked by immunofluorescent staining, real-time PCR, and Western blotting. Serum acetate level was examined by gas chromatographic analysis. The distribution of gut microbiota was measured by 16S ribosomal DNA sequencing with faeces. Results: Our results demonstrated that GPR43 expression was increased in kidney samples of DN patients, diabetic animal models, and high glucose-stimulated podocytes. Interestingly, deletion of GPR43 alleviated albuminuria and renal injury in diabetic mice. Pharmacological inhibition and knockdown of GPR43 expression in podocytes increased insulin-induced Akt phosphorylation through the restoration of adenosine 5'-monophosphate-activated protein kinase α (AMPKα) activity. This effect was associated with the suppression of AMPKα activity through post-transcriptional phosphorylation via the protein kinase C-phospholipase C (PKC-PLC) pathway. Antibiotic treatment-mediated gut microbiota depletion, and faecal microbiota transplantation from the healthy donor controls substantially improved podocyte insulin sensitivity and attenuated glomerular injury in diabetic rats accompanied by the downregulation of the GPR43 expression and a decrease in the level of serum acetate. Conclusion: These findings suggested that dysbiosis of gut microbiota-modulated GPR43 activation contributed to albuminuria in DN, which could be mediated by podocyte insulin resistance through the inhibition of AMPKα activity.}, }
@article {pmid33749411, year = {2022}, author = {Beyaz Coşkun, A and Sağdiçoğlu Celep, AG}, title = {Therapeutic modulation methods of gut microbiota and gut-liver axis.}, journal = {Critical reviews in food science and nutrition}, volume = {62}, number = {23}, pages = {6505-6515}, doi = {10.1080/10408398.2021.1902263}, pmid = {33749411}, issn = {1549-7852}, mesh = {Bile Acids and Salts ; *Gastrointestinal Microbiome ; Humans ; *Liver Diseases/therapy ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {Liver diseases are considered global health problems that cause more than 1 million deaths each year. Due to the increase in the prevalence of liver diseases worldwide, studies on different treatment methods have increased. Some of these methods is diagnostic and therapeutic applications based on the examination of the intestinal and intestinal microbiota. In this study, research articles, systematic review and review in the literature were examined in order to determine gut-liver axis relationship and treatment methods for liver diseases with gut modulation methods. Studies related to the subject have been searched in Google Scholar and Pubmed databases. The keywords "liver disease" and "gut-liver axis" and "microbiota" and "gut modulation methods" or "probiotic" or "prebiotic" or "symbiotic" or "antibiotic" or "bile acid regulation" or "adsorbent" or "fecal microbiota transplantation" were used in the searches. Improvements have been achieved in biomarkers of liver diseases by providing intestinal modulation with probiotic, prebiotic, symbiotic, antibiotic and adsorbents applications, bile acid regulation and fecal microbiota transplantation. In the results of experimental and clinical studies, it was seen that the therapeutic potential of the treatments performed by applying probiotics, prebiotics and symbiotics was higher.}, }
@article {pmid33748913, year = {2022}, author = {Tixier, EN and Verheyen, E and Luo, Y and Grinspan, LT and Du, CH and Ungaro, RC and Walsh, S and Grinspan, AM}, title = {Systematic Review with Meta-Analysis: Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile.}, journal = {Digestive diseases and sciences}, volume = {67}, number = {3}, pages = {978-988}, pmid = {33748913}, issn = {1573-2568}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Severe and fulminant Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality. While fecal microbiota transplantation (FMT) has proved to be a highly effective treatment for recurrent CDI, its efficacy in severe or fulminant CDI remains uncertain.<br><br>AIMS: To perform a systematic review with meta-analysis evaluating clinical outcomes and safety of FMT in severe and fulminant CDI.<br><br>METHODS: A systemic review with meta-analysis was performed through comprehensive search of Embase, Medline (Ovid), trial registers, and conference abstracts through January 2020. Studies on FMT in severe and fulminant CDI were included. Meta-analysis was done with random effects models given heterogeneity to estimate rates of cure, mortality, and colectomy. Publication bias was assessed using Egger's test.<br><br>RESULTS: Sixteen studies comprised of one randomized controlled trial, four cohort studies, and eleven case series were analyzed. In total, 676 patients underwent FMT for severe or fulminant CDI. The overall rate of clinical cure after single FMT was 61.3% (95% CI 43.2-78.0%) with 10.9% (95% CI 0.2-30.2%) of patients experiencing major adverse events. The overall pooled colectomy rate after FMT was 8.2% (95% CI 0.1-23.7%) with a pooled all-cause mortality rate after FMT of 15.6% (95% CI 7.8-25.0%).<br><br>CONCLUSION: Low-quality data support the use of fecal microbiota transplantation in patients with severe and fulminant Clostridioides difficile infection.}, }
@article {pmid33747125, year = {2021}, author = {Sehgal, K and Khanna, S}, title = {Gut microbiome and Clostridioides difficile infection: a closer look at the microscopic interface.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {1756284821994736}, pmid = {33747125}, issn = {1756-283X}, abstract = {The pathogenesis of Clostridioides difficile infection (CDI) was recognized with its link to the use of antimicrobials. Antimicrobials significantly alter gut microbiota structure and composition, which led to the discovery of the association of this gut perturbation with the development of CDI. A number of factors implicated in its pathogenesis, such as advancing age, proton-pump inhibitors, and gastrointestinal diseases, are linked to gut microbiota perturbations. In an effort to better understand CDI, a multitude of studies have tried to ascertain protective and predictive microbial footprints linked with CDI. It has further been realized that CDI in itself can alter the gut microbiome. Its spore-forming capability poses as an impediment in the management of the infection and contributes to its recurrence. Antibiotic therapies used for its management have also been linked to gut microbiota changes, making its treatment a little more challenging. In an effort to exploit and utilize this association, gut microbial restoration therapies, particularly in the form of fecal microbial transplant, are increasingly being put to use and are proving to be beneficial. In this review, we summarize the association of the gut microbiome and microbial perturbation with initial and recurrent CDI.}, }
@article {pmid33744860, year = {2021}, author = {Lianqun, J and Xing, J and Yixin, M and Si, C and Xiaoming, L and Nan, S and Guoyuan, S and Yuan, C and Ning, Y and Yao, W and Na, Z and Kaixuan, Z and Guanlin, Y}, title = {Comprehensive multiomics analysis of the effect of ginsenoside Rb1 on hyperlipidemia.}, journal = {Aging}, volume = {13}, number = {7}, pages = {9732-9747}, pmid = {33744860}, issn = {1945-4589}, mesh = {Animals ; Body Weight/drug effects ; Disease Models, Animal ; Ginsenosides/pharmacology/*therapeutic use ; Hyperlipidemias/*drug therapy/metabolism ; Lipid Metabolism/*drug effects ; Liver/drug effects/metabolism ; Mice ; Proteomics ; }, abstract = {We analyzed the effects of ginsenoside Rb1 on hyperlipidemic in model mice. Using stool, plasma and hepatic tissue samples, we observed that the genera Blautia and Allobaculum were increased and Turicibacter was decrease in Rb1-treated mice as compared to untreated model mice. Ether lipid metabolism, glycerolipid metabolism, and glyoxylate and dicarboxylate metabolism were differentially enriched between the Rb1 and model groups. Lipidomics revealed 169 metabolites differentially expressed between the model and Rb1 groups in a positive ion model and 58 in a negative ion model. These metabolites mainly participate in glycerophospholipid, linoleic acid, and alpha-linolenic acid metabolism. The main metabolites enriched in these three pathways were phosphatidylcholine, diacylglycerol and ceramide, respectively. In a transcriptome analysis, 766 transcripts were differentially expressed between the Rb1 and model groups. KEGG analysis revealed lysine degradation, inositol phosphate metabolism, and glycerophospholipid metabolism to be the main enriched pathways. Multiomics analysis revealed glycerophospholipid metabolism to be a common pathway and phosphatidylcholine the main metabolite differentially enriched between the Rb1 and model groups. Results from fecal transplanted germ-free mice suggest that to suppress hyperlipidemia, Rb1 regulates gut microbiota by regulating the synthesis and decomposition of phosphatidylcholine in glycerophospholipid metabolism, which in turn decreases serum total cholesterol.}, }
@article {pmid33744565, year = {2021}, author = {Chu, Q and Zhang, S and Yu, X and Wang, Y and Zhang, M and Zheng, X}, title = {Fecal microbiota transplantation attenuates nano-plastics induced toxicity in Caenorhabditis elegans.}, journal = {The Science of the total environment}, volume = {779}, number = {}, pages = {146454}, doi = {10.1016/j.scitotenv.2021.146454}, pmid = {33744565}, issn = {1879-1026}, mesh = {Animals ; *Caenorhabditis elegans ; Caenorhabditis elegans Proteins ; *Fecal Microbiota Transplantation ; Microplastics/*toxicity ; }, abstract = {Current studies simply focus on the toxicity of nano-plastics, while the correlation between their toxicity and bio-distribution, as well as intestinal microorganisms is still blank. Therefore, we systematically evaluated the toxicity based on the accumulation characteristics of nano-plastics in C. elegans. Meanwhile, for the first time, human fecal microbiota was transplanted into the gut of C. elegans and found that nano-plastics can through the intestinal barrier to the whole body after oral intake and can't be drastically excreted until die, thus causing toxic effects; while human fecal microbiota transplantation can significantly improve the living state via activating PMK-1/SKN-1 pathway to promote the production of intracellular glutathione, and exogenous glutathione addition can also markedly protect nematodes against nano-plastics induced toxicity. Our results not only provide a fully understand between the accumulation characteristic and health risk of nano-plastics, but also take C. elegans and intestinal flora into the field of toxicity evolution of nanomaterials.}, }
@article {pmid33744169, year = {2021}, author = {Bestfater, C and Vehreschild, MJGT and Stallmach, A and Tüffers, K and Erhardt, A and Frank, T and Glück, T and Goeser, F and Sellge, G and Solbach, P and Eisenlohr, H and Storr, M and , }, title = {Clinical effectiveness of bidirectional fecal microbiota transfer in the treatment of recurrent Clostridioides difficile infections.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {53}, number = {6}, pages = {706-711}, doi = {10.1016/j.dld.2021.02.022}, pmid = {33744169}, issn = {1878-3562}, mesh = {Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Registries ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transfer (FMT) has become a standard of care in the prevention of multiple recurrent Clostridioides difficile (rCDI) infection.<br><br>AIM: While primary cure rates range from 70-80% following a single treatment using monodirectional approaches, cure rates of combination treatment remain largely unknown.<br><br>METHODS: In a retrospective case-control study, outcomes following simultaneous bidirectional FMT (bFMT) with combined endoscopic application into the upper and lower gastrointestinal tract, compared to standard routes of application (endoscopy via upper or lower gastrointestinal tract and oral capsules; abbreviated UGIT, LGIT and CAP) on day 30 and 90 after FMT were assessed. Statistical matching partners were identified using number of recurrences (<3; &#x2265;3), age and gender.<br><br>RESULTS: Primary cure rates at D30 and D90 for bFMT were 100% (p=.001). The matched control groups showed cure rates of 81.3% for LGIT (p=.010), 62.5% for UGIT (p=.000) and 78.1% for CAP (p=.005) on D30 and 81.3% for LGIT (p=.010), 59.4% for UGIT (p=.000) and 71.9% for CAP (p=.001) on D90.<br><br>CONCLUSION: In our analysis, bFMT on the same day significantly increased primary cure rate at D30 and D90. These data require prospective confirmation but suggest that route of application may play a significant role in optimizing patient outcomes. ClinicalTrials.gov no: NCT02681068.}, }
@article {pmid33743988, year = {2021}, author = {Ahmad, H and Halleran, DR and Vardanyan, J and Mathieu, W and Stanek, J and Ranalli, M and Levitt, MA and Wood, RJ and Aldrink, JH}, title = {Functional fecal and urinary outcomes after sacrococcygeal mass resection in pediatric patients.}, journal = {Journal of pediatric surgery}, volume = {56}, number = {6}, pages = {1142-1147}, doi = {10.1016/j.jpedsurg.2021.02.028}, pmid = {33743988}, issn = {1531-5037}, mesh = {*Anorectal Malformations/surgery ; Child ; Constipation/etiology ; *Fecal Incontinence/epidemiology/etiology ; Female ; Humans ; Retrospective Studies ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Sacrococcygeal masses (SCM) are uncommon in children. The purpose of this study is to review the functional fecal and urinary outcomes following resection of SCM and to determine the impact of a multidisciplinary clinic (MDC) on these outcomes.<br><br>METHODS: A retrospective review was performed of patients who underwent SCM resection between 1979 and 2019. Baylor Social Continence Scale (BCS), Vancouver Symptom Score (VSS) and Cleveland constipation score (CSS) surveys were used to assess fecal and urinary continence at time of most recent follow up. Age, tumor characteristics, histopathology, and type of anorectal malformations (ARM), if present, were also recorded.<br><br>RESULTS: 75 patients were included. 51 (69%) patients were females and 23 (31%) had an associated ARM. The median age at resection was 8.5 months (IQR 0-26.8). 41 (56%) patients were followed in the MDC. 27 (82%) of patients seen in the MDC were clean for stool and 26 (87%) were dry for urine, while only 17 (59%) of patients not seen in the MDC were clean for stool and dry for urine (p<0.05). There was improvement in Baylor, Vancouver and Cleveland scores.<br><br>CONCLUSIONS: A multidisciplinary approach to the care of patients following SCM resection may improve bowel and bladder outcomes.}, }
@article {pmid33742731, year = {2021}, author = {Rao, J and Xie, R and Lin, L and Jiang, J and Du, L and Zeng, X and Li, G and Wang, C and Qiao, Y}, title = {Fecal microbiota transplantation ameliorates gut microbiota imbalance and intestinal barrier damage in rats with stress-induced depressive-like behavior.}, journal = {The European journal of neuroscience}, volume = {53}, number = {11}, pages = {3598-3611}, doi = {10.1111/ejn.15192}, pmid = {33742731}, issn = {1460-9568}, mesh = {Animals ; Brain ; Depression/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Rats ; Stress, Psychological/therapy ; }, abstract = {The gut-microbiota-brain axis is the most important complex and bidirectional pathway between the gastrointestinal tract and the central nervous system. This study investigated the potential of microbe-induced gut-to-brain signaling to modulate the effect of stress on depressive-like behavior, intestinal barrier, and neuroinflammation. Result showed that fecal microbiota transplantation increased the consumption of sucrose solutions and decreased the immobility time in forced swimming test. This treatment also increased Firmicutes and decreased Bacteroidetes and Desulfobacterota at phylum levels; reduced the loss of villi and epithelial cells; suppressed the inflammatory cell infiltration in the ileum; increased the expression of ZO-1, occludin; protected the mucosal layer function; and suppressed the high levels of inflammasomes (NLRP3, ASC, caspase-1, and IL-1β) in rat brain. In summary, fecal microbiota transplantation improves the depressive-like behavior, alters the gut microbiota imbalance, and alleviates the intestinal tract inflammation, intestinal mucosa disruption, and neuroinflammation in rats induced by chronic unpredictable mild stress.}, }
@article {pmid33741982, year = {2021}, author = {Agranyoni, O and Meninger-Mordechay, S and Uzan, A and Ziv, O and Salmon-Divon, M and Rodin, D and Raz, O and Koman, I and Koren, O and Pinhasov, A and Navon-Venezia, S}, title = {Gut microbiota determines the social behavior of mice and induces metabolic and inflammatory changes in their adipose tissue.}, journal = {NPJ biofilms and microbiomes}, volume = {7}, number = {1}, pages = {28}, pmid = {33741982}, issn = {2055-5008}, mesh = {Adipose Tissue/immunology/*metabolism ; Animals ; Bacteria/*classification/genetics/isolation &amp; purification ; Behavior, Animal/physiology ; Body Weight ; Depression/*microbiology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Germ-Free Life ; Male ; Mice ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA/*methods ; *Social Behavior ; }, abstract = {The link between the gut microbiota and social behavior has been demonstrated, however the translational impact of a certain microbiota composition on stable behavioral patterns is yet to be elucidated. Here we employed an established social behavior mouse model of dominance (Dom) or submissiveness (Sub). A comprehensive 16S rRNA gene sequence analysis of Dom and Sub mice revealed a significantly different gut microbiota composition that clearly distinguishes between the two behavioral modes. Sub mice gut microbiota is significantly less diverse than that of Dom mice, and their taxa composition uniquely comprised the genera Mycoplasma and Anaeroplasma of the Tenericutes phylum, in addition to the Rikenellaceae and Clostridiaceae families. Conversely, the gut microbiota of Dom mice includes the genus Prevotella of the Bacteriodetes phylum, significantly less abundant in Sub mice. In addition, Sub mice show lower body weight from the age of 2 weeks and throughout their life span, accompanied with lower epididymis white adipose tissue (eWAT) mass and smaller adipocytes together with substantially elevated expression of inflammation and metabolic-related eWAT adipokines. Finally, fecal microbiota transplantation into germ-free mice show that Sub-transplanted mice acquired Sub microbiota and adopted their behavioral and physiological features, including depressive-like and anti-social behaviors alongside reduced eWAT mass, smaller adipocytes, and a Sub-like eWAT adipokine profile. Our findings demonstrate the critical role of the gut microbiome in determining dominance vs. submissiveness and suggest an association between gut microbiota, the eWAT metabolic and inflammatory profile, and the social behavior mode.}, }
@article {pmid33738808, year = {2021}, author = {Xi, W and Gao, X and Zhao, H and Luo, X and Li, J and Tan, X and Wang, L and Zhao, JB and Wang, J and Yang, G and Liu, LY and Wang, YY and Peng, L and Zou, LP and Yang, Y}, title = {Depicting the composition of gut microbiota in children with tic disorders: an exploratory study.}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {62}, number = {10}, pages = {1246-1254}, doi = {10.1111/jcpp.13409}, pmid = {33738808}, issn = {1469-7610}, mesh = {Bacteroides ; Child ; *Gastrointestinal Microbiome ; Humans ; Prevotella ; Ruminococcus ; Streptococcus ; *Tic Disorders ; }, abstract = {BACKGROUND: Symptom improvement in children with tic disorder (TD) following fecal microbiota transplantation led us to investigate the gut microbiota in TD. This exploratory study aims to depict the gut microbial profile in patients with TD and explore the impact of dopamine receptor antagonist (DRA) drugs on the composition and metabolic function of the gut microbiota.<br><br>METHODS: The gut microbiota were profiled in fecal samples of 49 children with TD and 50 matched healthy controls (HC) using shotgun metagenomic sequencing. A random forest (RF) model was constructed using the gut bacterial species to distinguish TD from HC. Associations between clinical metadata and microbial abundance or function were analyzed using MaAsLin2 and Spearman correlation.<br><br>RESULTS: The gut microbiota in children with TD was featured by higher abundances of Bacteroides plebeius and Ruminococcus lactaris (a potential pro-inflammatory taxon) and lower abundances of Prevotella stercorea and Streptococcus lutetiensis compared to HC. The constructed RF model accurately distinguished TD from HC based on the gut microbiota profile, resulting in an AUC of 0.884. Significant correlations were observed between tic symptom severity and the abundances of multiple bacterial species and gut microbiota metabolic functions. Multivariate analysis identified an upregulation of 4-aminobutanoate (GABA) degradation in the gut microbiota associated with TD status. The gut microbiota of DRA-treated TD children showed a distinct gut microbiota compared to the treatment-na&#xef;ve group, represented by an increase in some potential enteric pathogens such as Escherichia coli, a decline in several species including Akkermansia muciniphila, and alterations in various metabolic functions.<br><br>CONCLUSIONS: Bacterial species promoting inflammatory responses and those modulating neurotransmitters such as GABA may be involved in the pathogenesis of TD. The use of DRA drugs is likely to induce overgrowth of some enteric pathogens and alter the gut microbiota metabolism.}, }
@article {pmid33734496, year = {2021}, author = {Li, H and Zhuang, P and Zhang, Y and Shou, Q and Lu, Y and Wang, G and Qiu, J and Wang, J and He, L and Chen, J and Jiao, J}, title = {Mixed conjugated linoleic acid sex-dependently reverses high-fat diet-induced insulin resistance via the gut-adipose axis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {4}, pages = {e21466}, doi = {10.1096/fj.202002161RR}, pmid = {33734496}, issn = {1530-6860}, mesh = {Adipose Tissue/*metabolism ; Animals ; Body Weight/drug effects ; *Diet, High-Fat ; Gastrointestinal Microbiome/*drug effects/physiology ; Insulin Resistance/*physiology ; Linoleic Acids, Conjugated/*pharmacology ; Lipid Metabolism/drug effects ; Mice, Inbred C57BL ; Obesity/metabolism ; Mice ; }, abstract = {Conjugated linoleic acid (CLA) may prevent the development of obesity and metabolic disorders. However, the effects of CLA on inflammation and glucose metabolism are controversial. The underlying mechanisms governing the gut microbiota and sexual dimorphisms have also not been elucidated. The present study assessed the effect of CLA on glucose and lipid metabolism in established obesity and examined the mechanism of action based on gut microbiota. Four-week-old C57BL/6J mice were fed a high-fat diet (HFD) for 10 weeks to induce obesity. The diet-induced obese (DIO) mice were fed an HFD supplemented with mixed CLA (50% cis-9, trans-11 isomer and 50% trans-10, cis-12 isomers, 0.2% wt/wt) for 15 weeks. CLA supplementation remarkably reversed body weight in both sexes. CLA favored anti-inflammatory microbiota in male mice, mediating increased short-chain fatty acids and decreased lipopolysaccharide (LPS) production, which alleviated global inflammation and improved insulin sensitivity via inhibition of the TLR4-NF-κB pathway in adipose tissue. CLA promoted the growth of hydrogen sulfide-producing Desulfovibrio and the release of LPS in female mice, which aggravated adipose inflammation and insulin resistance. Although CLA impaired glucose metabolism in females, brown adipose tissue was significantly activated with browning of white adipose tissue in both sexes, which led to enhanced energy expenditure. Fecal transplantation from CLA-treated mice to DIO mice mimicked the sex-dependent phenotype. In conclusion, CLA decreased body weight and increased energy expenditure but sex-dependently modulated insulin resistance via the gut-adipose axis.}, }
@article {pmid33734316, year = {2021}, author = {Teaw, S and Hinchcliff, M and Cheng, M}, title = {A review and roadmap of the skin, lung and gut microbiota in systemic sclerosis.}, journal = {Rheumatology (Oxford, England)}, volume = {60}, number = {12}, pages = {5498-5508}, pmid = {33734316}, issn = {1462-0332}, support = {R01 AR073270/AR/NIAMS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; /NH/NIH HHS/United States ; R01AR073270//National Institute of Arthritis, Musculoskeletal and Skin Disease/ ; }, mesh = {Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Lung/*microbiology ; Scleroderma, Systemic/*microbiology ; Skin/*microbiology ; }, abstract = {As our understanding of the genetic underpinnings of SSc increases, questions regarding the environmental trigger(s) that induce and propagate SSc in the genetically predisposed individual emerge. The interplay between the environment, the immune system, and the microbial species that inhabit the patient's skin and gastrointestinal tract is a pathobiological frontier that is largely unexplored in SSc. The purpose of this review is to provide an overview of the methodologies, experimental study results and future roadmap for elucidating the relationship between the SSc host and his/her microbiome.}, }
@article {pmid33731795, year = {2021}, author = {Kim, JK and Han, SK and Joo, MK and Kim, DH}, title = {Buspirone alleviates anxiety, depression, and colitis; and modulates gut microbiota in mice.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {6094}, pmid = {33731795}, issn = {2045-2322}, mesh = {Animals ; *Anxiety/drug therapy/microbiology ; Buspirone/*pharmacology ; *Colitis/drug therapy/microbiology ; *Depression/drug therapy/microbiology ; Escherichia coli/*metabolism ; *Escherichia coli Infections/drug therapy/microbiology ; Gastrointestinal Microbiome/*drug effects ; Male ; Mice ; }, abstract = {Gut microbiota regulate the neurodevelopmental processes and brain functions through the regulation of the microbiota-gut interaction and gut-brain communication. Buspirone, an agonist for serotonin 5-HT1A receptors, is used for the treatment of anxiety/depression. Therefore, to understand the gut microbiota-mediated mechanism of buspirone on anxiety/depression, we examined its effect on the immobilization stress (IS) or Escherichia coli K1 (EC)-induced anxiety/depression in mice. Oral or intraperitoneal administration of buspirone significantly suppressed stressor-induced anxiety/depression-like behaviors in the elevated plus maze, light/dark transition, tail suspension, and forced swimming tasks. Their treatments also reduced TNF-α expression and NF-κB[+]/Iba1[+] cell population in the hippocampus and myeloperoxidase activity and NF-κB[+]/CD11c[+] cell population in the colon. Buspirone treatments partially restored IS- or EC-induced gut microbiota perturbation such as β-diversity to those of normal control mice: they reduced the IS- or EC-induced gut Proteobacteria population. In particular, the anxiolytic activity of buspirone was positively correlated with the populations of Bacteroides and PAC001066_g in EC- or IS-exposed mice, while the populations of Lachnospiraceae, KE159660_g, LLKB_g, Helicobacter, and PAC001228_g were negatively correlated. The anti-depressant effect of buspirone was positively correlated with the Roseburia population. The fecal microbiota transplantations from buspirone-treated mice with IS-induced anxiety/depression or normal control mice suppressed IS-induced anxiety/depression-like behaviors and reduced hippocampal NF-κB[+]/Iba1[+] and colonic NF-κB[+]/CD11c[+] cell populations in the transplanted mice. Furthermore, they modified IS-induced perturbation of gut microbiota composition, particularly Proteobacteria, in the transplanted mice. In conclusion, buspirone alleviates IS as well as EC-induced anxiety/depression and colitis. It also suppresses associated neuroinflammation and modulates gut microbiota. Future studies can help to explain the relationship, if any, in the central and peripheral effects of buspirone.}, }
@article {pmid33729663, year = {2022}, author = {Khakisahneh, S and Zhang, XY and Nouri, Z and Wang, DH}, title = {Cecal microbial transplantation attenuates hyperthyroid-induced thermogenesis in Mongolian gerbils.}, journal = {Microbial biotechnology}, volume = {15}, number = {3}, pages = {817-831}, pmid = {33729663}, issn = {1751-7915}, mesh = {Animals ; Cecum/microbiology ; Gerbillinae/metabolism ; *Hyperthyroidism/therapy ; *Thermogenesis/physiology ; Thyroid Hormones/metabolism ; }, abstract = {Endothermic mammals have a high energy cost to maintain a stable and high body temperature (Tb , around 37°C). Thyroid hormones are a major regulator for energy metabolism and Tb . The gut microbiota is involved in modulating host energy metabolism. However, whether the interaction between the gut microbiota and thyroid hormones is involved in metabolic and thermal regulations is unclear. We hypothesized that thyroid hormones via an interaction with gut microbiota orchestrate host thermogenesis and Tb . l-thyroxine-induced hyperthyroid Mongolian gerbils (Meriones unguiculatus) increased resting metabolic rate (RMR) and Tb , whereas Methimazole-induced hypothyroid animals decreased RMR. Both hypothyroid and hyperthyroid animals differed significantly in faecal bacterial community. Hyperthyroidism increased the relative abundance of pathogenic bacteria, such as Helicobacter and Rikenella, and decreased abundance of beneficial bacteria Butyricimonas and Parabacteroides, accompanied by reduced total bile acids and short-chain fatty acids. Furthermore, the hyperthyroid gerbils transplanted with the microbiota from control donors increased type 2 deiodinase (DIO2) expression in the liver and showed a greater rate of decline of both serum T3 and T4 levels and, consequently, a more rapid recovery of normal RMR and Tb . These findings indicate that thyroid hormones regulate thermogenesis depending on gut microbiota and colonization with normal microbiota by caecal microbial transplantation attenuates hyperthyroid-induced thermogenesis. This work reveals the functional consequences of the gut microbiota-thyroid axis in controlling host metabolic physiology and Tb in endotherms.}, }
@article {pmid33727402, year = {2021}, author = {Jin, G and Tang, Q and Ma, J and Liu, X and Zhou, B and Sun, Y and Pang, X and Guo, Z and Xie, R and Liu, T and Wang, B and Cao, H}, title = {Maternal Emulsifier P80 Intake Induces Gut Dysbiosis in Offspring and Increases Their Susceptibility to Colitis in Adulthood.}, journal = {mSystems}, volume = {6}, number = {2}, pages = {}, pmid = {33727402}, issn = {2379-5077}, abstract = {Early life events can lead to multiple diseases in adulthood. Previous studies suggested that polysorbate 80 (P80) as a widely used emulsifier in pharmaceutical formulations and food industries could impair the intestinal barrier. However, whether maternal P80 (MP80) exposure could affect the long-term health of offspring remains unknown. In this study, we found that maternal P80 intake could retard intestinal development, disrupt the intestinal barrier, and cause low-grade intestinal inflammation in 3-week-old offspring. 16S rRNA sequencing and correlation analysis revealed that Mucispirillum, Clostridium XI, and Parabacteroides, which positively correlated with intestinal proliferation and differentiation, were decreased in the maternal P80 group. Interestingly, the increase in some harmful bacteria, including Proteobacteria, Helicobacteraceae, Campylobacterales, and Desulfovibrionales, persisted from the weaning period to adulthood (3 to 8 weeks). Furthermore, a fecal microbiota transplantation assay showed that the mice gavaged with feces from 3-week-old offspring of the MP80 group presented more severe intestinal inflammation and barrier disruption than the mice that received feces from the offspring of the control group. Finally, maternal P80 intake remarkably aggravated the structural disorder of intestinal crypt, increased proinflammatory factors, and exacerbated dextran sulfate sodium (DSS)-induced colitis in adulthood. Conclusively, maternal P80 intake could induce gut dysbiosis and promote colitis susceptibility in adulthood. This study provides new insights into the prevention of inflammatory bowel disease (IBD).IMPORTANCE The main findings of this research showed that maternal P80 intake could disrupt the intestinal barrier, induce gut dysbiosis, and promote colitis susceptibility in adulthood. This study will enhance understanding of the prevention of IBD.}, }
@article {pmid33725748, year = {2021}, author = {Chok, KC and Ng, KY and Koh, RY and Chye, SM}, title = {Role of the gut microbiome in Alzheimer's disease.}, journal = {Reviews in the neurosciences}, volume = {32}, number = {7}, pages = {767-789}, doi = {10.1515/revneuro-2020-0122}, pmid = {33725748}, issn = {2191-0200}, mesh = {*Alzheimer Disease ; Brain ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; }, abstract = {Alzheimer's disease (AD) is the most common form of dementia, affecting millions of individuals each year and this number is expected to significantly increase. The complicated microorganisms residing in human gut are closely associated with our health. Emerging evidence has suggested possible involvement of human gut microbiome in AD. Symbiotic gut microbiomes are known to maintain brain health by modulating host's barriers integrity, metabolic system, immune system, nervous system and endocrine system. However, in the event of gut dysbiosis and barriers disruption, gut pathobionts disrupt homeostasis of the metabolic system, immune system, nervous system, and endocrine system, resulting in deterioration of neurological functions and subsequently promoting development of AD. Multiple therapeutic approaches, such as fecal microbiome transplant, antibiotics, prebiotics, probiotics, symbiotic, and diet are discussed as potential treatment options for AD by manipulating the gut microbiome to reverse pathological alteration in the systems above.}, }
@article {pmid33723543, year = {2021}, author = {Gilca-Blanariu, GE and Stefanescu, G and Girleanu, I and Iqbal, T and Segal, J and Mullish, B and Quraishi, MN and Keller, J and Molnar, T and Megraud, F and Dumitrascu, D and Manuc, M and Iancu, LS and Marica, C and Gheorghe, C and Manzoor, S and Trifan, A}, title = {Romanian National Guideline on Translating Fecal Microbiota Transplantation Applications related to Clostridioides difficile Infections into the Local Clinical Practice.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {30}, number = {1}, pages = {147-163}, doi = {10.15403/jgld-3297}, pmid = {33723543}, issn = {1842-1121}, mesh = {Clostridioides difficile ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods/standards ; Feces/microbiology ; Humans ; Practice Guidelines as Topic ; Romania ; }, abstract = {Fecal microbiota transplantation involves the infusion of intestinal microorganisms via the transfer of a stool from a healthy individual into a diseased individual, with the intent of restoring normal intestinal flora. Fecal transplant is proposed for the treatment of refractory Clostridioides difficile infection. At present, recurrent Clostridioides difficile infection is the only indication supported by solid scientific evidence. Regulations by healthcare authorities vary among different countries. Considering that Romania does not have an available national guideline to offer standardization, this paper aimed to create a national fecal microbiota transplantation guideline concerning indications, techniques and donor screening, developed by international and local scientific working groups.}, }
@article {pmid33722710, year = {2021}, author = {Alghetaa, H and Mohammed, A and Zhou, J and Singh, N and Nagarkatti, M and Nagarkatti, P}, title = {Resveratrol-mediated attenuation of superantigen-driven acute respiratory distress syndrome is mediated by microbiota in the lungs and gut.}, journal = {Pharmacological research}, volume = {167}, number = {}, pages = {105548}, pmid = {33722710}, issn = {1096-1186}, support = {R01 ES030144/ES/NIEHS NIH HHS/United States ; P20 GM103641/GM/NIGMS NIH HHS/United States ; P01 AT003961/AT/NCCIH NIH HHS/United States ; R01 AT006888/AT/NCCIH NIH HHS/United States ; R01 AI123947/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Cell Line ; Colon/*drug effects/immunology/metabolism/microbiology ; Cytokines/metabolism ; Disease Models, Animal ; Dysbiosis ; *Enterotoxins ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects ; Inflammation Mediators/metabolism ; Limosilactobacillus reuteri/drug effects/growth &amp; development ; Lung/*drug effects/immunology/metabolism/microbiology ; Mice, Inbred C3H ; Respiratory Distress Syndrome/immunology/metabolism/microbiology/*prevention &amp; control ; Resveratrol/*pharmacology ; *Superantigens ; Mice ; }, abstract = {Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of agents, including Staphylococcal Enterotoxin B (SEB). Interestingly, a significant proportion of patients with COVID-19, also develop ARDS. In the absence of effective treatments, ARDS results in almost 40% mortality. Previous studies from our laboratory demonstrated that resveratrol (RES), a stilbenoid, with potent anti-inflammatory properties can attenuate SEB-induced ARDS. In the current study, we investigated the role of RES-induced alterations in the gut and lung microbiota in the regulation of ARDS. Our studies revealed that SEB administration induced inflammatory cytokines, ARDS, and 100% mortality in C3H/HeJ mice. Additionally, SEB caused a significant increase in pathogenic Proteobacteria phylum and Propionibacterium acnes species in the lungs. In contrast, RES treatment attenuated SEB-mediated ARDS and mortality in mice, and significantly increased probiotic Actinobacteria phylum, Tenericutes phylum, and Lactobacillus reuteri species in both the colon and lungs. Colonic Microbiota Transplantation (CMT) from SEB-injected mice that were treated with RES as well as the transfer of L. reuteri into recipient mice inhibited the production of SEB-mediated induction of pro-inflammatory cytokines such as IFN-γ and IL-17 but increased that of anti-inflammatory IL-10. Additionally, such CMT and L. reuteri recipient mice exposed to SEB, showed a decrease in lung-infiltrating mononuclear cells, cytotoxic CD8+ T cells, NKT cells, Th1 cells, and Th17 cells, but an increase in the population of regulatory T cells (Tregs) and Th3 cells, and increase in the survival of mice from SEB-mediated ARDS. Together, the current study demonstrates that ARDS induced by SEB triggers dysbiosis in the lungs and gut and that attenuation of ARDS by RES may be mediated, at least in part, by alterations in microbiota in the lungs and the gut, especially through the induction of beneficial bacteria such as L. reuteri.}, }
@article {pmid33722220, year = {2021}, author = {Tang, X and Wang, W and Hong, G and Duan, C and Zhu, S and Tian, Y and Han, C and Qian, W and Lin, R and Hou, X}, title = {Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency.}, journal = {Journal of biomedical science}, volume = {28}, number = {1}, pages = {20}, pmid = {33722220}, issn = {1423-0127}, support = {81330014//National Natural Science Foundation of China/ ; 81974068//National Natural Science Foundation of China/ ; 81900580//National Natural Science Foundation of China/ ; 81800467//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Bacteria/*metabolism ; Colitis/*microbiology ; Fucosyltransferases/*deficiency ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/metabolism ; Lysophosphatidylcholines/*metabolism ; Mice ; Mice, Transgenic ; Galactoside 2-alpha-L-fucosyltransferase ; }, abstract = {BACKGROUND AND AIMS: Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD.<br><br>METHODS: Intestinal epithelium-specific Fut2 knockout (Fut2[&#x25b3;IEC]) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis.<br><br>RESULTS: The expression of Fut2 and &#x3b1;-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P&#x2009;=&#x2009;0.036) and CD (CD vs. control, P&#x2009;=&#x2009;0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2[&#x25b3;IEC] mice was noted. Lower gut microbiota diversity was observed in Fut2[&#x25b3;IEC] mice compared with WT mice (p&#x2009;<&#x2009;0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2[&#x25b3;IEC] mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2[&#x25b3;IEC] mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria-Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo.<br><br>CONCLUSION: Fut2 and &#x3b1;-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2[&#x25b3;IEC] mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.}, }
@article {pmid33718398, year = {2021}, author = {Delli Bovi, AP and Marciano, F and Mandato, C and Siano, MA and Savoia, M and Vajro, P}, title = {Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {595371}, pmid = {33718398}, issn = {2296-858X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it remains still orphan of an adequate therapeutic strategy. Herein we focus on the interplay between oxidative stress (OS) and the other causal pathogenetic factors. Different reactive oxygen species (ROS) generators contribute to NAFLD inflammatory and fibrotic progression, which is quite strictly linked to the lipotoxic liver injury from fatty acids and/or a wide variety of their biologically active metabolites in the context of either a two-hit or a (more recent) multiple parallel hits theory. An antioxidant defense system is usually able to protect hepatic cells from damaging effects caused by ROS, including those produced into the gastrointestinal tract, i.e., by-products generated by usual cellular metabolic processes, normal or dysbiotic microbiota, and/or diet through an enhanced gut-liver axis. Oxidative stress originating from the imbalance between ROS generation and antioxidant defenses is under the influence of individual genetic and epigenetic factors as well. Healthy diet and physical activity have been shown to be effective on NAFLD also with antioxidant mechanisms, but compliance to these lifestyles is very low. Among several considered antioxidants, vitamin E has been particularly studied; however, data are still contradictory. Some studies with natural polyphenols proposed for NAFLD prevention and treatment are encouraging. Probiotics, prebiotics, diet, or fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors will likely assist in further selecting the treatment that could work best for a specific patient.}, }
@article {pmid33718277, year = {2021}, author = {Żebrowska, P and Łaczmańska, I and Łaczmański, &#x141;}, title = {Future Directions in Reducing Gastrointestinal Disorders in Children With ASD Using Fecal Microbiota Transplantation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {630052}, pmid = {33718277}, issn = {2235-2988}, mesh = {*Autism Spectrum Disorder ; Child ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases ; }, abstract = {Research on the use of fecal microbiota transplantation (FMT) in the treatment of disorders related to digestive system ailments in children with autism spectrum disorders (ASDs) is a new attempt in a therapeutic approach. There are very little scientific evidences available on this emerging alternative method. However, it appears to be interesting not only because of its primary outcome, relieving the gastrointestinal (GI) symptoms, but also secondary therapeutic effect of alleviating autistic behavioral symptoms. FMT seems to be also promising method in the treatment of another group of pediatric patients, children with inflammatory bowel disease (IBD). The aim of this study is to discuss the potential use of FMT and modified protocols (MTT, microbiota transfer therapy) in the treatment of GI disorders in ASD children supported by reports on another disease, IBD concerning pediatric patients. Due to the few reports of the use of FMT in the treatment of children, these two patients groups were selected, although suffering from distant health conditions: neurodevelopmental disorder and gastrointestinal tract diseases, because of the the fact that they seem related in aspects of the presence of GI symptoms, disturbed intestinal microbiota, unexplained etiology of the condition and age range of patients. Although the outcomes for all are promising, this type of therapy is still an under-researched topic, studies in the group of pediatric patients are sparse, also there is a high risk of transmission of infectious and noninfectious elements during the procedure and no long-term effects on global health are known. For those reasons all obtained results should be taken with a great caution. However, in the context of future therapeutic directions for GI observed in neurodevelopmental disorders and neurodegenerative diseases, the topic seems worthy of attention.}, }
@article {pmid33716293, year = {2021}, author = {Koninckx, CR and Donat, E and Benninga, MA and Broekaert, IJ and Gottrand, F and Kolho, KL and Lionetti, P and Miele, E and Orel, R and Papadopoulou, A and Pienar, C and Schäppi, MG and Wilschanski, M and Thapar, N}, title = {The Use of Fecal Calprotectin Testing in Paediatric Disorders: A Position Paper of the European Society for Paediatric Gastroenterology and Nutrition Gastroenterology Committee.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {72}, number = {4}, pages = {617-640}, doi = {10.1097/MPG.0000000000003046}, pmid = {33716293}, issn = {1536-4801}, mesh = {Child ; Feces ; *Gastroenterology ; *Gastrointestinal Diseases/diagnosis ; *Helicobacter Infections ; *Helicobacter pylori ; Humans ; Infant, Newborn ; Leukocyte L1 Antigen Complex ; }, abstract = {OBJECTIVES: The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children.<br><br>METHODS: A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors.<br><br>RESULTS: A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9.<br><br>CONCLUSIONS: Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Sch&#xf6;nlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.}, }
@article {pmid33714825, year = {2021}, author = {Desdouits, M and Piquet, JC and Wacrenier, C and Le Mennec, C and Parnaudeau, S and Jousse, S and Rocq, S and Bigault, L and Contrant, M and Garry, P and Chavanon, F and Gabellec, R and Lamort, L and Lebrun, L and Le Gall, P and Meteigner, C and Schmitt, A and Seugnet, JL and Serais, O and Peltier, C and Bressolette-Bodin, C and Blanchard, Y and Le Guyader, FS}, title = {Can shellfish be used to monitor SARS-CoV-2 in the coastal environment?.}, journal = {The Science of the total environment}, volume = {778}, number = {}, pages = {146270}, pmid = {33714825}, issn = {1879-1026}, mesh = {Animals ; *COVID-19 ; France ; Humans ; *Norovirus ; SARS-CoV-2 ; Shellfish ; Swine ; }, abstract = {The emergence and worldwide spread of SARS-CoV-2 raises new concerns and challenges regarding possible environmental contamination by this virus through spillover of human sewage, where it has been detected. The coastal environment, under increasing anthropogenic pressure, is subjected to contamination by a large number of human viruses from sewage, most of them being non-enveloped viruses like norovirus. When reaching coastal waters, they can be bio-accumulated by filter-feeding shellfish species such as oysters. Methods to detect this viral contamination were set up for the detection of non-enveloped enteric viruses, and may need optimization to accommodate enveloped viruses like coronaviruses (CoV). Here, we aimed at assessing methods for the detection of CoV, including SARS-CoV-2, in the coastal environment and testing the possibility that SARS-CoV-2 can contaminate oysters, to monitor the contamination of French shores by SARS-CoV-2 using both seawater and shellfish. Using the porcine epidemic diarrhea virus (PEDV), a CoV, as surrogate for SARS-CoV-2, and Tulane virus, as surrogate for non-enveloped viruses such as norovirus, we assessed and selected methods to detect CoV in seawater and shellfish. Seawater-based methods showed variable and low yields for PEDV. In shellfish, the current norm for norovirus detection was applicable to CoV detection. Both PEDV and heat-inactivated SARS-CoV-2 could contaminate oysters in laboratory settings, with a lower efficiency than a calicivirus used as control. Finally, we applied our methods to seawater and shellfish samples collected from April to August 2020 in France, where we could detect the presence of human norovirus, a marker of human fecal contamination, but not SARS-CoV-2. Together, our results validate methods for the detection of CoV in the coastal environment, including the use of shellfish as sentinels of the microbial quality of their environment, and suggest that SARS-CoV-2 did not contaminate the French shores during the summer season.}, }
@article {pmid33713592, year = {2021}, author = {Cortés, P and Bi, Y and Stancampiano, F and Valery, JR and Cooper, JH and Harris, DM}, title = {Clostridioides difficile infection: a comprehensive review for primary providers.}, journal = {Romanian journal of internal medicine = Revue roumaine de medecine interne}, volume = {59}, number = {3}, pages = {262-269}, doi = {10.2478/rjim-2021-0010}, pmid = {33713592}, issn = {2501-062X}, mesh = {Clostridioides difficile/*isolation &amp; purification ; *Clostridium Infections/diagnosis/epidemiology/therapy ; *Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection (CDI) is an issue of great concern due to its rising incidence, recurrence, morbidity and impact on healthcare spending. Treatment guidelines have changed in the last few years, and new therapies are being considered. This is a practical review for the primary care practitioner of the latest guidelines for CDI diagnosis, treatment, and emerging therapies.}, }
@article {pmid33711509, year = {2021}, author = {Qian, XH and Song, XX and Liu, XL and Chen, SD and Tang, HD}, title = {Inflammatory pathways in Alzheimer's disease mediated by gut microbiota.}, journal = {Ageing research reviews}, volume = {68}, number = {}, pages = {101317}, doi = {10.1016/j.arr.2021.101317}, pmid = {33711509}, issn = {1872-9649}, mesh = {*Alzheimer Disease/therapy ; Amyloid ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; }, abstract = {In the past decade, numerous studies have demonstrated the close relationship between gut microbiota and the occurrence and development of Alzheimer's disease (AD). However, the specific mechanism is still unclear. Both the neuroinflammation and systemic inflammation serve as the key hubs to accelerate the process of AD by promoting pathology and damaging neuron. What's more, the gut microbiota is also crucial for the regulation of inflammation. Therefore, this review focused on the role of gut microbiota in AD through inflammatory pathways. Firstly, this review summarized the relationship and interaction among gut microbiota, inflammation, and AD. Secondly, the direct and indirect regulatory effects of gut microbiota on AD through inflammatory pathways were described. These effects were mainly mediated by the component of the gut microbiota (lipopolysaccharides (LPS) and amyloid peptides), the metabolites of bacteria (short-chain fatty acids, branched amino acids, and neurotransmitters) and functional by-products (bile acids). In addition, potential treatments (fecal microbiota transplantation, antibiotics, probiotics, prebiotics, and dietary interventions) for AD were also discussed through these mechanisms. Finally, according to the current research status, the key problems to be solved in the future studies were proposed.}, }
@article {pmid33711435, year = {2021}, author = {Long, D and Liu, M and Li, H and Song, J and Jiang, X and Wang, G and Yang, X}, title = {Dysbacteriosis induces abnormal neurogenesis via LPS in a pathway requiring NF-κB/IL-6.}, journal = {Pharmacological research}, volume = {167}, number = {}, pages = {105543}, doi = {10.1016/j.phrs.2021.105543}, pmid = {33711435}, issn = {1096-1186}, mesh = {Animals ; Chick Embryo ; Dysbiosis/*immunology/physiopathology/therapy ; Fecal Microbiota Transplantation ; Female ; Interleukin-6/*immunology ; Lipopolysaccharides/*immunology ; Male ; Mice, Inbred C57BL ; NF-kappa B/*immunology ; *Neurogenesis ; *Signal Transduction ; Mice ; }, abstract = {In this study, we identified elevated levels of LPS and suppressed neurogenesis in a successfully established mouse model of gut microbiota dysbiosis. We mimicked these phenotypes using mouse and chicken embryos exposed to LPS and found that dramatic variation in gene expression was due to changes in the dorsal-ventral patterning of the neural tube. Cell survival and excess ROS were also involved in this process. Antioxidant administration alleviated LPS-activated NF-κB signaling, while directly blocking NF-κB signaling altered the LPS-induced inhibition of neurogenesis. Furthermore, IL-6 was proven to play a vital role in the expression of crucial neurogenesis-related genes and NF-κB. In summary, we found that the suppression of neurogenesis induced by dysbacteriosis-derived LPS was significantly reversed in mice with fecal microbiota transplantation. This study reveals that gut dysbacteriosis-derived LPS impairs embryonic neurogenesis, and that the NF-κB/IL-6 pathway could be one of the main factors triggering the downstream signaling cascade.}, }
@article {pmid33708514, year = {2021}, author = {Song, A and Shen, N and Gan, C and Luo, C and Luo, C and Wang, J and Cao, Q and Chen, J}, title = {Exploration of the relationship between intestinal flora changes and gut acute graft-versus-host disease after hematopoietic stem cell transplantation.}, journal = {Translational pediatrics}, volume = {10}, number = {2}, pages = {283-295}, pmid = {33708514}, issn = {2224-4344}, abstract = {BACKGROUND: Acute graft-versus-host disease (aGVHD) is a life-threatening factor for post-hematopoietic stem cell transplantation (HSCT) patients. To investigate the relationship between intestinal flora changes and gut aGVHD after HSCT, we performed this cross-sectional study.<br><br>METHODS: We selected children from our medical center from July 2016 to January 2017. Fifty-six samples from 42 patients and 6 samples from normal children met the study criteria and were analyzed. Fecal 16S RNA sequencing was completed before transplantation or on days 7, 28 or 100 post-transplantation. The intestinal infection and GVHD clinical data were retrospectively analyzed, and the survival risk factors were analyzed. Correlation analysis was performed with the feces bioinformatic data.<br><br>RESULTS: The GVHD group alpha diversity was the lowest, which was significantly different than that of the non-diarrhea group (P value=0.032). A richer posttransplantation relative abundance of Moraxellaceae was conducive to survival, while that of Enterococcaceae and Alphaproteobacteria was not. Similarly, a rich relative abundance of Proteobacteria, Gammaproteobacteria and Odoribacteraceae in the intestinal flora before HSCT contributed to patient death thereafter. Regarding diarrhea, the GVHD group exhibited a richer Pasteurellales and Pasteurellaceae relative abundances, which showed strong correlations with diarrhea severity. Peptostreptococcaceae, Bifidobacteriales and Bifidobacteriaceae were richer in relative abundance in the intestinal infection group and correlated with pretransplant characteristics.<br><br>CONCLUSIONS: The gut microbiota diversity was lowest when gut aGVHD occurred, which was consistent with the clinically higher mortality rate and greater treatment difficulty. Pasteurellaceae played an important role in gut aGVHD and diarrhea severity. Bifidobacteriaceae led to infectious diarrhea after HSCT. Specific bacteria were biomarkers for survival: Moraxellaceae, Enterococcaceae and Alphaproteobacteria from the intestinal flora after HSCT and Proteobacteria, Gammaproteobacteria and Odoribacteraceae before HSCT.}, }
@article {pmid33708182, year = {2021}, author = {Su, Y and Li, X and Li, D and Sun, J}, title = {Fecal Microbiota Transplantation Shows Marked Shifts in the Multi-Omic Profiles of Porcine Post-weaning Diarrhea.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {619460}, pmid = {33708182}, issn = {1664-302X}, abstract = {Weaning is the most critical phase in pig production and is generally associated with significant impacts on intestinal morphology, structure, physiology, and immune responses, which can lead to subsequent production inefficiencies such as decreases in growth and intake and increases in morbidity and mortality. In the present study, we attempted to explore the effects of fecal microbiota transplantation (FMT) on the fecal microbiota, fecal metabolites, and transcriptome in the jejunum, colon, liver, spleen, and oral mucosa in piglets with post-weaning diarrhea and to evaluate the therapeutic potential of FMT in piglets with post-weaning diarrhea. We found that FMT partially relieved the symptoms of diarrhea in piglets, and microbiota analysis results indicated that unclassified_f_Prevotellaceae was identified as an FMT-associated bacterial family at 66 day and that the Shannon index in the healthy group at 34, 38, and 66 days were higher than that at 21 day. Functional enrichment analysis of the oral mucosa, liver, jejunum, and colon showed that most of the differentially expressed genes (DEGs) were enriched in the terms metabolic process, immune response, and inflammatory response. Moreover, the enriched fecal metabolites focused mostly on apoptosis, beta-alanine metabolism, glutathione metabolism, and sphingolipid metabolism. We tried to detect specific "metabolite-bacterium" pairs, such as "g_Catenisphaera-stigmastentriol," "p_Bacteroidetes-(6beta,22E)-6-hydroxystigmasta-4,22-dien-3-one," and "g_Prevotellaceae_NK3B31_group-stenocereol." Overall, the present study provides a theoretical basis for the alleviation of weaning stress and contributes to the realization of effective and sustainable application of FMT in the pig production industry in the future.}, }
@article {pmid33705752, year = {2021}, author = {Wang, G and Hu, YX and He, MY and Xie, YH and Su, W and Long, D and Zhao, R and Wang, J and Dai, C and Li, H and Si, ZP and Cheng, X and Li, RM and Li, Z and Yang, X}, title = {Gut-Lung Dysbiosis Accompanied by Diabetes Mellitus Leads to Pulmonary Fibrotic Change through the NF-κB Signaling Pathway.}, journal = {The American journal of pathology}, volume = {191}, number = {5}, pages = {838-856}, doi = {10.1016/j.ajpath.2021.02.019}, pmid = {33705752}, issn = {1525-2191}, mesh = {Animals ; Anti-Infective Agents/administration &amp; dosage ; Diabetes Mellitus, Experimental/chemically induced/*complications/pathology ; Disease Models, Animal ; Dysbiosis/chemically induced/*complications/pathology/therapy ; Fecal Microbiota Transplantation ; Flavonoids/administration &amp; dosage ; Gastrointestinal Microbiome ; Intestines/microbiology/pathology ; Lincomycin/adverse effects ; Lung/microbiology/pathology ; Mice ; Mice, Inbred C57BL ; *Microbiota ; NF-kappa B/genetics/*metabolism ; Pulmonary Fibrosis/etiology/*microbiology/pathology/therapy ; *Signal Transduction ; Streptozocin/adverse effects ; }, abstract = {Growing evidence shows that the lungs are an unavoidable target organ of diabetic complications. However, the pathologic mechanisms of diabetic lung injury are still controversial. This study demonstrated the dysbiosis of the gut and lung microbiome, pulmonary alveolar wall thickening, and fibrotic change in streptozotocin-induced diabetic mice and antibiotic-induced gut dysbiosis mice compared with controls. In both animal models, the NF-κB signaling pathway was activated in the lungs. Enhanced pulmonary alveolar well thickening and fibrotic change appeared in the lungs of transgenic mice expressing a constitutively active NF-κB mutant compared with wild type. When lincomycin hydrochloride-induced gut dysbiosis was ameliorated by fecal microbiota transplant, enhanced inflammatory response in the intestine and pulmonary fibrotic change in the lungs were significantly decreased compared with lincomycin hydrochloride-treated mice. Furthermore, the application of fecal microbiota transplant and baicalin could also redress the microbial dysbiosis of the gut and lungs in streptozotocin-induced diabetic mice. Taken together, these data suggest that multiple as yet undefined factors related to microbial dysbiosis of gut and lungs cause pulmonary fibrogenesis associated with diabetes mellitus through an NF-κB signaling pathway.}, }
@article {pmid33705688, year = {2021}, author = {Buffington, SA and Dooling, SW and Sgritta, M and Noecker, C and Murillo, OD and Felice, DF and Turnbaugh, PJ and Costa-Mattioli, M}, title = {Dissecting the contribution of host genetics and the microbiome in complex behaviors.}, journal = {Cell}, volume = {184}, number = {7}, pages = {1740-1756.e16}, pmid = {33705688}, issn = {1097-4172}, support = {T32 AI060537/AI/NIAID NIH HHS/United States ; R01 DK114034/DK/NIDDK NIH HHS/United States ; R01 MH112356/MH/NIMH NIH HHS/United States ; P30 ES030285/ES/NIEHS NIH HHS/United States ; R25 GM056929/GM/NIGMS NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification ; Biopterins/analogs &amp; derivatives/metabolism ; Disease Models, Animal ; Excitatory Postsynaptic Potentials ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Limosilactobacillus reuteri/metabolism/physiology ; *Locomotion ; Membrane Proteins/deficiency/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Tissue Proteins/deficiency/genetics ; Neurodevelopmental Disorders/genetics/microbiology/pathology/therapy ; Principal Component Analysis ; Psychomotor Agitation/pathology ; *Social Behavior ; Synaptic Transmission ; }, abstract = {The core symptoms of many neurological disorders have traditionally been thought to be caused by genetic variants affecting brain development and function. However, the gut microbiome, another important source of variation, can also influence specific behaviors. Thus, it is critical to unravel the contributions of host genetic variation, the microbiome, and their interactions to complex behaviors. Unexpectedly, we discovered that different maladaptive behaviors are interdependently regulated by the microbiome and host genes in the Cntnap2[-/-] model for neurodevelopmental disorders. The hyperactivity phenotype of Cntnap2[-/-] mice is caused by host genetics, whereas the social-behavior phenotype is mediated by the gut microbiome. Interestingly, specific microbial intervention selectively rescued the social deficits in Cntnap2[-/-] mice through upregulation of metabolites in the tetrahydrobiopterin synthesis pathway. Our findings that behavioral abnormalities could have distinct origins (host genetic versus microbial) may change the way we think about neurological disorders and how to treat them.}, }
@article {pmid33704807, year = {2021}, author = {Koretz, RL}, title = {JPEN Journal Club 61. Testing hypotheses.}, journal = {JPEN. Journal of parenteral and enteral nutrition}, volume = {45}, number = {7}, pages = {1604-1606}, doi = {10.1002/jpen.2099}, pmid = {33704807}, issn = {1941-2444}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Metabolic Syndrome ; }, }
@article {pmid33704802, year = {2021}, author = {Gu, M and Samuelson, DR and Taylor, CM and Molina, PE and Luo, M and Siggins, RW and Shellito, JE and Welsh, DA}, title = {Alcohol-associated intestinal dysbiosis alters mucosal-associated invariant T-cell phenotype and function.}, journal = {Alcoholism, clinical and experimental research}, volume = {45}, number = {5}, pages = {934-947}, pmid = {33704802}, issn = {1530-0277}, support = {P60 AA009803/AA/NIAAA NIH HHS/United States ; K99-AA026336/AA/NIAAA NIH HHS/United States ; R21 AA027199/AA/NIAAA NIH HHS/United States ; K99 AA026336/AA/NIAAA NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; U54- GM104940/GM/NIGMS NIH HHS/United States ; P50 AA009803/AA/NIAAA NIH HHS/United States ; R24 AA019661/AA/NIAAA NIH HHS/United States ; UH2 AA026226/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcoholism/*immunology ; Animals ; Anti-Bacterial Agents/pharmacology ; Antigens, CD/drug effects/metabolism ; Antigens, Differentiation, T-Lymphocyte/drug effects/metabolism ; Binge Drinking/*immunology ; Central Nervous System Depressants/*pharmacology ; Dysbiosis/*immunology ; Ethanol/*pharmacology ; Fecal Microbiota Transplantation ; Flow Cytometry ; *Gastrointestinal Microbiome ; Intestinal Mucosa/cytology ; Lectins, C-Type/drug effects/metabolism ; Liver/cytology/immunology ; Lung/cytology/immunology ; Mice ; Mucosal-Associated Invariant T Cells/*drug effects/immunology ; }, abstract = {BACKGROUND: Chronic alcohol consumption is associated with a compromised innate and adaptive immune responses to infectious disease. Mucosa-associated invariant T (MAIT) cells play a critical role in antibacterial host defense. However, whether alcohol-associated deficits in innate and adaptive immune responses are mediated by alterations in MAIT cells remains unclear.<br><br>METHODS: To investigate the impact of alcohol on MAIT cells, mice were treated with binge-on-chronic alcohol for 10&#xa0;days and sacrificed at day 11. MAIT cells in the barrier organs (lung, liver, and intestine) were characterized by flow cytometry. Two additional sets of animals were used to examine the involvement of gut microbiota on alcohol-induced MAIT cell changes: (1) Cecal microbiota from alcohol-fed (AF) mice were adoptive transferred into antibiotic-pretreated mice and (2) AF mice were treated with antibiotics during the experiment. MAIT cells in the barrier organs were measured via flow cytometry.<br><br>RESULTS: Binge-on-chronic alcohol feeding led to a significant reduction in the abundance of MAIT cells in the barrier tissues. However, CD69 expression on tissue-associated MAIT cells was increased in AF mice compared with pair-fed (PF) mice. The expression of Th1 cytokines and the corresponding transcriptional factor was tissue specific, showing downregulation in the intestine and increases in the lung and liver in AF animals. Transplantation of fecal microbiota from AF mice resulted in a MAIT cell profile aligned to that of AF mouse donor. Antibiotic treatment abolished the MAIT cell differences between AF and PF animals.<br><br>CONCLUSION: MAIT cells in the intestine, liver, and lung are perturbed by alcohol use and these changes are partially attributable to alcohol-associated dysbiosis. MAIT cell dysfunction may contribute to alcohol-induced innate and adaptive immunity and consequently end-organ pathophysiology.}, }
@article {pmid33704562, year = {2021}, author = {Fritz, S and Hennig, R and Kantas, C and Killguss, H and Schaudt, A and Feilhauer, K and Köninger, J}, title = {The transverse coloplasty pouch is technically easy and safe and improves functional outcomes after low rectal cancer resection-a single center experience with 397 patients.}, journal = {Langenbeck's archives of surgery}, volume = {406}, number = {3}, pages = {833-841}, pmid = {33704562}, issn = {1435-2451}, mesh = {Anal Canal/surgery ; Anastomosis, Surgical ; Colon/surgery ; *Colonic Pouches ; Humans ; Postoperative Complications/epidemiology ; *Proctocolectomy, Restorative ; *Rectal Neoplasms/surgery ; Rectum/surgery ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Following resection for low rectal cancer, numerous patients suffer from frequent bowel movements, fecal urgency, and incontinence. Although there is good evidence that colonic J-pouch reconstruction, side-to-end anastomosis, or a transverse coloplasty pouch (TCP) improves functional outcome, many surgeons still prefer straight coloanal anastomosis because it is technically easier and lacks the risk of pouch-associated complications. The present single-center study aimed to evaluate the practicability of TCPs in routine clinical practice as well as pouch-related complications.<br><br>METHOD: All consecutive patients who underwent low anterior rectal resection with restoration of bowel continuity for cancer during the period September 2008 to June 2018 were included. A TCP in combination with a diverting ileostomy was defined as the hospital standard. The feasibility and safety of TCPs were assessed in a retrospective single-center study.<br><br>RESULTS: A total of 397 patients were included in the study. A total of 328/397 patients underwent TCP construction (82.6%). Two pouch-related surgical complications occurred (0.6%); one case of pouch-related stenosis and one case of sutural insufficiency. Overall, leakage of the coloanal anastomosis was reported in 14.1% of patients with a TCP and in 18.8% of patients without a pouch (p=0.252). Diverting ileostomy was applied in 378/397 patients (95.2%). The 30-day mortality was 0.25%.<br><br>CONCLUSION: The present study is by far the largest single-center experience with TCP construction for low rectal cancer resection. The study shows that a TCP is technically applicable in the vast majority of cases (82.6%). Pouch-associated surgical complications are sporadic events. In our opinion, the TCP can be considered an alternative to J-pouch construction after low anterior rectal resection.}, }
@article {pmid33694229, year = {2021}, author = {Rode, AA and Chehri, M and Krogsgaard, LR and Heno, KK and Svendsen, AT and Ribberholt, I and Helms, M and Engberg, J and Schønning, K and Tvede, M and Andersen, C&#xd8; and Jensen, US and Petersen, AM and Bytzer, P}, title = {Randomised clinical trial: a 12-strain bacterial mixture versus faecal microbiota transplantation versus vancomycin for recurrent Clostridioides difficile infections.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {53}, number = {9}, pages = {999-1009}, doi = {10.1111/apt.16309}, pmid = {33694229}, issn = {1365-2036}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Feces ; Humans ; Recurrence ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: A defined bacterial mixture could be a safer alternative to faecal microbiota transplantation (FMT).<br><br>AIMS: To compare the efficacy of a 12-strain mixture termed rectal bacteriotherapy with either FMT or vancomycin for recurrent Clostridioides difficile infection (CDI) in an open-label 3-arm randomised controlled trial.<br><br>METHODS: We screened all individuals positive for C difficile from May 2017 to March 2019. Persons with laboratory-confirmed recurrent CDI were included. Before FMT and rectal bacteriotherapy, we pre-treated with vancomycin for 7-14&#xa0;days. Rectal bacteriotherapy was applied by enema on three consecutive days and FMT by enema once with possible repetition for two to three infusions within 14&#xa0;days. The vancomycin group was treated for 14&#xa0;days with additional five weeks of tapering for multiple recurrences. The primary outcome was clinical cure within 90&#xa0;days. A secondary outcome was 180-day all-cause mortality.<br><br>RESULTS: Participants in the FMT group (n&#xa0;=&#xa0;34) were cured more often than participants receiving vancomycin (n&#xa0;=&#xa0;31), 76% vs 45% (OR 3.9 (1.4-11.4), P&#xa0;<&#xa0;0.01) or rectal bacteriotherapy (n&#xa0;=&#xa0;31), 76% vs 52% (OR 3.0 (1.1-8.8), P&#xa0;=&#xa0;0.04). Rectal bacteriotherapy and vancomycin performed similarly (P&#xa0;=&#xa0;0.61). The mortality rate was 6% in the FMT group, 13% in the bacteriotherapy group and 23% in the vancomycin group. FMT tended to reduce mortality compared with vancomycin, OR 0.2 (0.04-1.12), P&#xa0;=&#xa0;0.07.<br><br>CONCLUSIONS: Rectal bacteriotherapy appears as effective as vancomycin but less effective than 1-3 FMTs. FMT by enema with 1-3 infusions is superior to vancomycin for treating recurrent C difficile infections and might reduce mortality.}, }
@article {pmid33692965, year = {2021}, author = {Kaiser, T and Nalluri, H and Zhu, Z and Staley, C}, title = {Donor Microbiota Composition and Housing Affect Recapitulation of Obese Phenotypes in a Human Microbiota-Associated Murine Model.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {614218}, pmid = {33692965}, issn = {2235-2988}, support = {R01 DK122056/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces ; *Housing ; Humans ; Mice ; *Microbiota ; Obesity ; Phenotype ; }, abstract = {Human microbiota-associated (HMA) mouse models offer a valuable approach to study the role of intestinal microbiota in the development of obesity. In this study, we used an HMA model to evaluate whether engraftment of human obese or lean microbiota, from each of three donors, could recapitulate host phenotypes under conventional and specific-pathogen-free housing. Microbiota engraftment was correlated with donor relative abundances of the class Bacteroidia (Spearman's ρ = 0.73, P ≤ 0.001), and one obese donor resulted in significant weight gain (P ≤ 0.003) and compromised insulin sensitivity under conventional housing. SPF housing partially blunted phenotypic response. Results of this study indicate that our HMA model partially recapitulates obese phenotypes under conventional housing and highlights a need to consider donor-specific effects as well as housing conditions when studying the role of the microbiota in obesity.}, }
@article {pmid33692964, year = {2021}, author = {Liu, J and Xu, Y and Jiang, B}, title = {Novel Insights Into Pathogenesis and Therapeutic Strategies of Hepatic Encephalopathy, From the Gut Microbiota Perspective.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {586427}, pmid = {33692964}, issn = {2235-2988}, mesh = {Brain ; Dysbiosis/therapy ; *Gastrointestinal Microbiome ; *Hepatic Encephalopathy/therapy ; Humans ; *Probiotics/therapeutic use ; }, abstract = {Since the 1950s, gradual changes in the gut microbiota of patients with hepatic encephalopathy have been observed. Previous research has indicated potential associations between the gut and brain, and the gut microbiota is becoming a hot topic in research on diseases of the nervous system. However, for the past few decades, studies of hepatic encephalopathy have been restricted to controlling the gut microbiota during macroscopic manipulation, such as probiotic intervention, while its clinical use remains controversial, and the cellular mechanisms underlying this condition are still poorly understood. This thesis seeks to comprehensively understand and explain the role of gut microbiota in hepatic encephalopathy as well as analyze the effects of intervention by regulating the gut microbiota. Evidence is presented that shows that dysbiosis of the gut microbiota is the primary pathological driver of hepatic encephalopathy and impacts pathologic progression via complex regulatory networks. As a result, suggestions were identified for future mechanistic research and improvements in therapeutic strategies for hepatic encephalopathy.}, }
@article {pmid33691599, year = {2021}, author = {Meng, Q and Ma, M and Zhang, W and Bi, Y and Cheng, P and Yu, X and Fu, Y and Chao, Y and Ji, T and Li, J and Chen, Q and Zhang, Q and Li, Y and Shan, J and Bian, H}, title = {The gut microbiota during the progression of atherosclerosis in the perimenopausal period shows specific compositional changes and significant correlations with circulating lipid metabolites.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-27}, pmid = {33691599}, issn = {1949-0984}, mesh = {Animals ; Atherosclerosis/*microbiology/*physiopathology ; Bacteria/growth &amp; development ; Diet, High-Fat ; Disease Progression ; Estradiol/administration &amp; dosage ; Estrogen Replacement Therapy ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; *Lipid Metabolism ; Lipids/blood ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Ovariectomy ; *Perimenopause ; }, abstract = {Atherosclerosis (AS) is exacerbated in the perimenopausal period, which significantly increases the incidence rate of cardiovascular disease. The disruption of the gut microbiota has been associated with AS or menopause, but the specific changes of AS-associated gut microbiota in the perimenopausal period remain largely unknown. As lipid abnormalities are mainly responsible for AS, the relationship between lipid metabolism abnormalities and gut microbiota disruptions during menopause is rarely reported hitherto. In the present study, ApoE[-/-] mice fed with a high-fat diet (HFD) were subjected to ovariectomy and supplemented with estrogen. The ovariectomized HFD-fed ApoE[-/-] mice underwent significant AS damage, hepatic lipid damage, hyperlipidemia, and changes of lipid metabolism- and transport-related enzymes. There was significantly higher abundance of some lipid metabolites in the plasma of ovariectomized HFD-fed ApoE[-/-] mice than in non-ovariectomized ones, including cholesterol esters, triglycerides, phospholipids, and other types of lipids (free fatty acids, acylcarnitine, sphingomyelins, and ceramides). The administration of estrogen significantly reduced the contents of most lipid metabolites. The diversity and composition of gut microbiota evidently changed in ovariectomized HFD-fed ApoE[-/-] mice, compared to HFD-fed ApoE[-/-] mice without ovariectomy. In contrast, with estrogen supplementation, the diversity and composition of gut microbiota were restored to approach that of non-ovariectomized HFD-fed ApoE[-/-] mice, and the relative abundances of some bacteria were even like those of C57BL/6 mice fed with a normal diet. On the other hand, the transplantation of feces from C57BL/6 mice fed with normal diet to ovariectomized HFD-fed ApoE[-/-] mice was sufficient to correct the hyperlipidemia and AS damage, and to reverse the characteristics changing of lipid metabolomics in ovariectomized HFD-fed ApoE[-/-] mice. These phenomena were also been observed after transplantation of feces from estrogen-treated ovariectomized HFD-fed ApoE[-/-] mice to ovariectomized HFD-fed ApoE[-/-] mice. Moreover, the gut microbiota and lipid metabolites were significantly correlated, demonstrating that the changes of serum lipids may be associated with the gut microbiota disruptions in the perimenopausal period. In conclusion, the gut microbiota during the progression of AS in the perimenopausal period showed specific compositional changes and significant correlations with circulating lipid metabolites. Estrogen supplementation may exert beneficial effects on gut bacteria and lipid metabolism.}, }
@article {pmid33687943, year = {2022}, author = {Lai, HC and Lin, TL and Chen, TW and Kuo, YL and Chang, CJ and Wu, TR and Shu, CC and Tsai, YH and Swift, S and Lu, CC}, title = {Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide.}, journal = {Gut}, volume = {71}, number = {2}, pages = {309-321}, doi = {10.1136/gutjnl-2020-322599}, pmid = {33687943}, issn = {1468-3288}, mesh = {Animals ; Bacteroidetes/*isolation &amp; purification ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Lipopolysaccharides/metabolism ; Mice ; Mice, Inbred C57BL ; Pulmonary Disease, Chronic Obstructive/*etiology/metabolism/pathology ; Smoking ; }, abstract = {OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.<br><br>DESIGN: A murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.<br><br>RESULTS: Gut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.<br><br>CONCLUSION: The gut microbiota-lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.}, }
@article {pmid33685067, year = {2021}, author = {Kaya, F and İnkaya, A&#xc7; and Aksoy, S and Abbasoğlu, O and Ertenli, A&#x130; and Büyükaşık, Y and Arıkan Akdağlı, S and Akyön, Y and Ergüven, S}, title = {Investigation of Intestinal Protozoon Prevalence in Immunocompromised Patients at a University Hospital.}, journal = {Turkiye parazitolojii dergisi}, volume = {45}, number = {1}, pages = {39-44}, doi = {10.4274/tpd.galenos.2020.6819}, pmid = {33685067}, issn = {2146-3077}, mesh = {Blastocystis/isolation &amp; purification ; Dientamoeba/isolation &amp; purification ; Entamoeba/isolation &amp; purification ; Feces/microbiology/parasitology ; Giardia/isolation &amp; purification ; Hospitals, University ; Humans ; *Immunocompromised Host ; Intestinal Diseases, Parasitic/*epidemiology/immunology/microbiology/*parasitology ; Microsporidia/isolation &amp; purification ; Prevalence ; }, abstract = {OBJECTIVE: Immunocompromised patients are at a greater risk of developing intestinal parasite infections. In this study, we examined the presence of Enterocytozoon bieneusi, Encaphalitozoon intestinalis and other intestinal protozoa in stool samples of immunosuppressed patients.<br><br>METHODS: A total of 100 stool samples were obtained from patients receiving chemotherapy because of solid organ tumour with haematological malignancies and those receiving immunosuppressive treatment because of rheumatic diseases, organ transplant patients and patients receiving treatment for HIV-related infections. Stool samples were examined by using the native-lugol method in which the stool concentration, modified Kinyoun acid-fast and trichrome staining methods and parasite presence were analysed. The stool samples were also examined for the presence of Enterocytozoon bieneusi and Encephalitozoon intestinalis using an indirect fluorescent antibody method.<br><br>RESULTS: Intestinal parasites were detected in 12% of all patients. The distribution of intestinal parasites in patients were 7% Blastocystis spp., 2% Blastocystis spp. + Dientamoeba fragilis, 1% Blastocystis spp. + Entamoeba coli, 1% Blastocystis spp. + Giardia intestinalis and 1% G. intestinalis. Microsporidia spp. were detected in 4% of all patients by the IFAT method and in 8% of all patients by calcoflour staining method.<br><br>CONCLUSION: In our study, the most prevalent parasite detected in the immunosuppressed patients was Blastocystis spp. The pathogenesis of Blastocystis spp. remains to be controversial, and their role in immunocompromised patients continues to remain unknown. Although these rates detected in our study are similar to the prevalence in the normal population, it is important to study these microorganisms in immunocompromised patients in terms of the associated decreasing morbidity and mortality rates.}, }
@article {pmid33682170, year = {2021}, author = {Gupta, S and Zhu, J and McCarty, TR and Pruce, J and Kassam, Z and Kelly, C and Fischer, M and Allegretti, JR}, title = {Cost-effectiveness analysis of sequential fecal microbiota transplantation for fulminant Clostridioides difficile infection.}, journal = {Journal of gastroenterology and hepatology}, volume = {36}, number = {9}, pages = {2432-2440}, doi = {10.1111/jgh.15483}, pmid = {33682170}, issn = {1440-1746}, support = {T32DK007533-35/DK/NIDDK NIH HHS/United States ; T32DK007533-35/DK/NIDDK NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Cost-Benefit Analysis ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIM: Fulminant Clostridioides difficile infections (FCDI) account for 8% of cases and substantial healthcare burden. Fecal microbiota transplantation is recommended for recurrent CDI, but emerging data support use for FCDI. We aimed to assess the cost-effectiveness of a sequential fecal microbiota transplantation (sFMT) protocol for FCDI compared with current standard therapy.<br><br>METHODS: A Markov model simulated patients with FCDI in a 1-year time horizon. The treatment algorithm for up to three sFMTs, clinical probabilities, and direct costs were used from published sources. Outcomes were quality-adjusted life years (QALYs) and costs. The healthcare sector perspective was used with a willingness-to-pay threshold of $100&#xa0;000 per QALY.<br><br>RESULTS: Sequential fecal microbiota transplantation (FMT) for FCDI was associated with lower overall cost ($28&#xa0;309 vs $33&#xa0;980) and higher QALY (0.765 vs 0.686) compared with standard therapy. sFMT is cost-effective in 100% of iterations. sFMT remained cost-effective at cure rates&#xa0;>&#xa0;44.8% for the first FMT and at stool preparation cost&#xa0;<&#xa0;$6944 per instillation. We find a wide range of efficacies for the first versus second FMT at which sFMT is still preferred. Value of information analysis estimates the expected value of perfect information to be low at $1.89 per person, quantified with net monetary benefit.<br><br>CONCLUSIONS: An sFMT strategy strongly dominates standard therapy, with lower cost and higher QALY. Sensitivity analysis demonstrates benefit even if FMT cure rates are lower than expected and when multiple FMTs are required. FMT material in 2020 was priced at $1695 per treatment but remains cost-effective at a much higher cost.}, }
@article {pmid33679632, year = {2021}, author = {Lee, LH and Wong, SH and Chin, SF and Singh, V and Ab Mutalib, NS}, title = {Editorial: Human Microbiome: Symbiosis to Pathogenesis.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {605783}, pmid = {33679632}, issn = {1664-302X}, }
@article {pmid33678185, year = {2021}, author = {Jing, Y and Yu, Y and Bai, F and Wang, L and Yang, D and Zhang, C and Qin, C and Yang, M and Zhang, D and Zhu, Y and Li, J and Chen, Z}, title = {Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {59}, pmid = {33678185}, issn = {2049-2618}, mesh = {Animals ; Brain/*physiology ; Fatty Acids, Volatile/metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry ; Female ; Gastrointestinal Microbiome/*physiology ; Interleukin-1beta/metabolism ; Intestines/microbiology/physiology ; Locomotion ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Neuroprotection/*physiology ; Signal Transduction ; Spinal Cord Injuries/pathology/*therapy ; }, abstract = {BACKGROUND: Spinal cord injury (SCI) patients display disruption of gut microbiome, and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) from healthy uninjured mice into SCI mice may exert a neuroprotective effect.<br><br>RESULTS: FMT facilitated functional recovery, promoted neuronal axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility in SCI mice. High-throughput sequencing revealed that levels of phylum Firmicutes, family Christensenellaceae, and genus Butyricimonas were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT downregulated IL-1&#x3b2;/NF-&#x3ba;B signaling in spinal cord and NF-&#x3ba;B signaling in gut following SCI.<br><br>CONCLUSION: Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs. Video Abstract.}, }
@article {pmid33677218, year = {2021}, author = {Rao, J and Qiao, Y and Xie, R and Lin, L and Jiang, J and Wang, C and Li, G}, title = {Fecal microbiota transplantation ameliorates stress-induced depression-like behaviors associated with the inhibition of glial and NLRP3 inflammasome in rat brain.}, journal = {Journal of psychiatric research}, volume = {137}, number = {}, pages = {147-157}, doi = {10.1016/j.jpsychires.2021.02.057}, pmid = {33677218}, issn = {1879-1379}, mesh = {Animals ; Brain/metabolism ; Depression/etiology/therapy ; Fecal Microbiota Transplantation ; *Inflammasomes/metabolism ; *NLR Family, Pyrin Domain-Containing 3 Protein ; Neuroglia ; Rats ; Stress, Psychological/therapy ; }, abstract = {BACKGROUND: Evidence from previous studies has demonstrated that the gut-microbiota-brain axis is vital in regulating of behavior and neuroinflammation in the central nervous system. Considering the putative connection among gut microbiota, neural function, and behavior, the present study investigated the potential signaling of gut microbiota to modulate depression-like behaviors and neuroinflammation.<br><br>METHODS: Rats showing depression-like behaviors induced by chronic unpredictable mild stress received fecal microbiota treatment or vehicle for 14 days, and alterations in behavior and neuroinflammation were assessed. ELISA, immunofluorescence staining and Western blot were used to analysis the activation of glial cells and NLRP3 inflammasome.<br><br>RESULTS: Treatment with fecal microbiota transplantation ameliorated depression-like behaviors. 5-Hydroxytryptamine decreased in the chronic unpredictable mild stress rat model but significantly increased after fecal microbiota transplantation. The treatment with fecal microbiota transplantation decreased the production of IL-1&#x3b2; and TNF-&#x3b1;. Moreover, fecal microbiota transplantation administration suppressed the activation of Iba1 positive microglia cells and GFAP positive astrocytes cells and reduced the expression of NLRP3, ASC, Caspase-1, and IL-1&#x3b2; pathway in the prefrontal cortex and hippocampus.<br><br>CONCLUSIONS: Fecal microbiota transplantation can improve depression-like behaviors induced by chronic unpredictable mild stress. The anti-depression effects of fecal microbiota transplantation were associated with the suppressed activation of glial cells and NLRP3 inflammasome in the brain.}, }
@article {pmid33674230, year = {2021}, author = {Zhou, CB and Zhou, YL and Fang, JY}, title = {Gut Microbiota in Cancer Immune Response and Immunotherapy.}, journal = {Trends in cancer}, volume = {7}, number = {7}, pages = {647-660}, doi = {10.1016/j.trecan.2021.01.010}, pmid = {33674230}, issn = {2405-8025}, mesh = {Adaptive Immunity ; Animals ; Anti-Bacterial Agents/adverse effects ; Combined Modality Therapy/methods ; Disease Models, Animal ; Disease-Free Survival ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*immunology ; Host Microbial Interactions/drug effects/*immunology ; Humans ; Immune Checkpoint Inhibitors/*administration &amp; dosage/adverse effects ; Immunotherapy/methods ; Mice ; Neoplasm Recurrence, Local/*epidemiology/immunology/prevention &amp; control ; Neoplasms/immunology/microbiology/mortality/*therapy ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; Prognosis ; Progression-Free Survival ; }, abstract = {The gastrointestinal tract (GIT) is the largest immune organ and maintains systemic immune homeostasis in the presence of bacterial challenge. Immune elimination and immune escape are hallmarks of cancer, both of which can be partly bacteria dependent in shaping immunity by mediating host immunomodulation. In addition, host immunity regulates the microbiome by altering bacteria-associated signaling to influence tumor surveillance. Cancer immunotherapy, including immune checkpoint blockade (ICB), appears to have heterogeneous therapeutic effects in different individuals, partially attributed to the microbiota. Thus, the microbiome signature can predict clinical outcomes, prognosis, and immunotherapy responses. In this review, we summarize the intricate crosstalk among the gut microbiome, cancer immune response, and immunotherapy. Interactive modulation of the host microbiota provides new therapeutic strategies to promote anticancer therapy efficacy and/or reduce toxicity.}, }
@article {pmid33670255, year = {2021}, author = {Verdier, C and Denis, S and Gasc, C and Boucinha, L and Uriot, O and Delmas, D and Dore, J and Le Camus, C and Schwintner, C and Blanquet-Diot, S}, title = {An Oral FMT Capsule as Efficient as an Enema for Microbiota Reconstruction Following Disruption by Antibiotics, as Assessed in an In Vitro Human Gut Model.}, journal = {Microorganisms}, volume = {9}, number = {2}, pages = {}, pmid = {33670255}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is an innovative therapy already used in humans to treat Clostridioides difficile infections associated with massive use of antibiotics. Clinical studies are obviously the gold standard to evaluate FMT efficiency but remain limited by regulatory, ethics, and cost constraints. In the present study, an in vitro model of the human colon reproducing medically relevant perturbation of the colonic ecosystem by antibiotherapy was used to compare the efficiency of traditional FMT enema formulations and a new oral capsule in restoring gut microbiota composition and activity. Loss of microbial diversity, shift in bacterial populations, and sharp decrease in fermentation activities induced in vivo by antibiotherapy were efficiently reproduced in the in vitro model, while capturing inter-individual variability of gut microbiome. Oral capsule was as efficient as enema to decrease the number of disturbed days and bacterial load had no effect on enema performance. This study shows the relevance of human colon models as an alternative approach to in vivo assays during preclinical studies for evaluating FMT efficiency. The potential of this in vitro approach could be extended to FMT testing in the management of many digestive or extra-intestinal pathologies where gut microbial dysbiosis has been evidenced such as inflammatory bowel diseases, obesity or cancers.}, }
@article {pmid33669988, year = {2021}, author = {Shabbir, U and Arshad, MS and Sameen, A and Oh, DH}, title = {Crosstalk between Gut and Brain in Alzheimer's Disease: The Role of Gut Microbiota Modulation Strategies.}, journal = {Nutrients}, volume = {13}, number = {2}, pages = {}, pmid = {33669988}, issn = {2072-6643}, support = {Grant No. 22A20153713433//Brain Korea (BK) 21 Plus Project/ ; }, mesh = {Alzheimer Disease/*microbiology ; Animals ; Blood-Brain Barrier/microbiology ; Brain/*microbiology ; Diet Therapy ; Dysbiosis/metabolism/psychology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestinal Mucosa/*metabolism ; Permeability ; Probiotics/therapeutic use ; }, abstract = {The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota-gut-brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer's disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood-brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.}, }
@article {pmid33669557, year = {2021}, author = {Giampaolino, P and Foreste, V and Di Filippo, C and Gallo, A and Mercorio, A and Serafino, P and Improda, FP and Verrazzo, P and Zara, G and Buonfantino, C and Borgo, M and Riemma, G and Angelis, C and Zizolfi, B and Bifulco, G and Della Corte, L}, title = {Microbiome and PCOS: State-of-Art and Future Aspects.}, journal = {International journal of molecular sciences}, volume = {22}, number = {4}, pages = {}, pmid = {33669557}, issn = {1422-0067}, mesh = {Animals ; Diet ; Female ; *Gastrointestinal Microbiome ; Genitalia, Female/microbiology ; Hormones/metabolism ; Humans ; Insulin Resistance ; Polycystic Ovary Syndrome/*microbiology/therapy ; }, abstract = {Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.}, }
@article {pmid33668518, year = {2021}, author = {Ciernikova, S and Mego, M and Chovanec, M}, title = {Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity.}, journal = {Cancers}, volume = {13}, number = {4}, pages = {}, pmid = {33668518}, issn = {2072-6694}, support = {APVV-19-0411 and APVV-15-0086//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja/ ; 2/0052/18 and 1/0327/19//Vedeck&#xe1; Grantov&#xe1; Agent&#xfa;ra M&#x160;VVa&#x160; SR a SAV/ ; }, abstract = {Chemotherapy, targeting not only malignant but also healthy cells, causes many undesirable side effects in cancer patients. Due to this fact, long-term cancer survivors often suffer from late effects, including cognitive impairment and cardiovascular toxicity. Chemotherapy damages the intestinal mucosa and heavily disrupts the gut ecosystem, leading to gastrointestinal toxicity. Animal models and clinical studies have revealed the associations between intestinal dysbiosis and depression, anxiety, pain, impaired cognitive functions, and cardiovascular diseases. Recently, a possible link between chemotherapy-induced gut microbiota disruption and late effects in cancer survivors has been proposed. In this review, we summarize the current understanding of preclinical and clinical findings regarding the emerging role of the microbiome and the microbiota-gut-brain axis in chemotherapy-related late effects affecting the central nervous system (CNS) and heart functions. Importantly, we provide an overview of clinical trials evaluating the relationship between the gut microbiome and cancer survivorship. Moreover, the beneficial effects of probiotics in experimental models and non-cancer patients with neurocognitive disorders and cardiovascular diseases as well as several studies on microbiota modulations via probiotics or fecal microbiota transplantation in cancer patients are discussed.}, }
@article {pmid33667294, year = {2021}, author = {Ranallo, RT and McDonald, LC and Halpin, AL and Hiltke, T and Young, VB}, title = {The State of Microbiome Science at the Intersection of Infectious Diseases and Antimicrobial Resistance.}, journal = {The Journal of infectious diseases}, volume = {223}, number = {12 Suppl 2}, pages = {S187-S193}, pmid = {33667294}, issn = {1537-6613}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; U54 CK000481/CK/NCEZID CDC HHS/United States ; U54 CK000607/CK/NCEZID CDC HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Antimicrobial Stewardship ; Communicable Diseases/diagnosis/immunology/*microbiology/therapy ; *Drug Resistance, Microbial ; Fecal Microbiota Transplantation ; Homeostasis ; Host-Pathogen Interactions ; Humans ; Immunity ; *Microbiota/drug effects ; }, abstract = {Along with the rise in modern chronic diseases, ranging from diabetes to asthma, there are challenges posed by increasing antibiotic resistance, which results in difficult-to-treat infections, as well as sepsis. An emerging and unifying theme in the pathogenesis of these diverse public health threats is changes in the microbial communities that inhabit multiple body sites. Although there is great promise in exploring the role of these microbial communities in chronic disease pathogenesis, the shorter timeframe of most infectious disease pathogenesis may allow early translation of our basic scientific understanding of microbial ecology and host-microbiota-pathogen interactions. Likely translation avenues include development of preventive strategies, diagnostics, and therapeutics. For example, as basic research related to microbial pathogenesis continues to progress, Clostridioides difficile infection is already being addressed clinically through at least 2 of these 3 avenues: targeted antibiotic stewardship and treatment of recurrent disease through fecal microbiota transplantation.}, }
@article {pmid33666892, year = {2021}, author = {El-Salhy, M and Patcharatrakul, T and Gonlachanvit, S}, title = {The role of diet in the pathophysiology and management of irritable bowel syndrome.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {40}, number = {2}, pages = {111-119}, pmid = {33666892}, issn = {0975-0711}, support = {40415//Helse Fonna/ ; }, mesh = {Diet ; Diet, Carbohydrate-Restricted ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/etiology ; Monosaccharides ; Quality of Life ; }, abstract = {Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder that reportedly affects 5% to 20% of the world population. The etiology of IBS is not completely understood, but diet appears to play an important role in its pathophysiology. Asian diets differ considerably from those in Western countries, which might explain differences in the prevalence, sex, and clinical presentation seen between patients with IBS in Asian and Western countries. Dietary regimes such as a low-fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) diet and the modified National Institute for Health and Care Excellence (NICE) diet improve both symptoms and the quality of life in a considerable proportion of IBS patients. It has been speculated that diet is a prebiotic for the intestinal microbiota and favors the growth of certain bacteria. These bacteria ferment the dietary components, and the products of fermentation act upon intestinal stem cells to influence their differentiation into enteroendocrine cells. The resulting low density of enteroendocrine cells accompanied by low levels of certain hormones gives rise to intestinal dysmotility, visceral hypersensitivity, and abnormal secretion. This hypothesis is supported by the finding that changing to a low-FODMAP diet restores the density of GI cells to the levels in healthy subjects. These changes in gut endocrine cells caused by low-FODMAP diet are also accompanied by improvements in symptoms and the quality of life.}, }
@article {pmid33663713, year = {2021}, author = {Kopper, JJ and Alexander, TL and Kogan, CJ and Berreta, AR and Burbick, CR}, title = {In Vitro Evaluation of the Effect of Storage at -20°C and Proximal Gastrointestinal Conditions on Viability of Equine Fecal Microbiota Transplant.}, journal = {Journal of equine veterinary science}, volume = {98}, number = {}, pages = {103360}, doi = {10.1016/j.jevs.2020.103360}, pmid = {33663713}, issn = {0737-0806}, mesh = {Animals ; Dysbiosis/veterinary ; Fecal Microbiota Transplantation/veterinary ; Feces ; *Gastrointestinal Microbiome ; *Horse Diseases ; Horses ; *Microbiota ; }, abstract = {Fecal microbiota transplant (FMT), a technique used to restore normal intestinal microbial communities, has been successful in treating humans with Clostridioides difficile colitis. Subsequently, FMT is being used in veterinary patients with suspected intestinal dysbiosis. Unfortunately, little data are available regarding best practices for FMT in horses. The objective of this study was to evaluate the effects of storing manure prepared for equine FMT (MP-FMT) at -20°C for up to 4 weeks and passage through a simulated proximal gastrointestinal (GI) tract on the viability of MP-FMT. The results of this study indicate that storage at -20°C for greater than 1 week and exposure to conditions consistent with the proximal GI tract significantly decreased viability of the microbial population, with gram-negative enteric bacteria most significantly impacted. This preliminary evaluation indicates that further work is necessary to determine best practices to preserve the viability MP-FMT in horses.}, }
@article {pmid33662679, year = {2021}, author = {Xu, JY and Liu, MT and Tao, T and Zhu, X and Fei, FQ}, title = {The role of gut microbiota in tumorigenesis and treatment.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {138}, number = {}, pages = {111444}, doi = {10.1016/j.biopha.2021.111444}, pmid = {33662679}, issn = {1950-6007}, mesh = {Animals ; Carcinogenesis/drug effects/*metabolism ; Cell Transformation, Neoplastic/drug effects/metabolism ; Dysbiosis/*metabolism/*therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/drug effects/*physiology ; Gastrointestinal Neoplasms/*metabolism/*therapy ; Humans ; Probiotics/administration &amp; dosage ; Treatment Outcome ; }, abstract = {A large number of microbial communities exist in normal human intestinal tracts, which maintain a relatively stable dynamic balance under certain conditions. Gut microbiota are closely connected with human health and the occurrence of tumors. The colonization of certain intestinal bacteria on specific sites, gut microbiota disturbance and intestinal immune disorders can induce the occurrence of tumors. Meanwhile, gut microbiota can also play a role in tumor therapy by participating in immune regulation, influencing the efficacy of anti-tumor drugs, targeted therapy of engineered probiotics and fecal microbiota transplantation. This article reviews the role of gut microbiota in the occurrence, development, diagnosis and treatment of tumors. A better understanding of how gut microbiota affect tumors will help us find more therapies to treat the disease.}, }
@article {pmid33660961, year = {2021}, author = {Mikolašević, I and Hauser, G and Abram, M and Filipec Kanižaj, T and Radić, M and Krznarić Zrnić, I}, title = {Fecal microbiota transplantation - where are we?.}, journal = {Croatian medical journal}, volume = {62}, number = {1}, pages = {52-58}, pmid = {33660961}, issn = {1332-8166}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Humans ; Treatment Outcome ; }, }
@article {pmid33659945, year = {2020}, author = {Khurana, S and Kahl, A and Yu, K and DuPont, AW}, title = {Recent advances in the treatment of Clostridioides difficile infection: the ever-changing guidelines.}, journal = {Faculty reviews}, volume = {9}, number = {}, pages = {13}, pmid = {33659945}, issn = {2732-432X}, abstract = {Clostridioides difficile infection (CDI), formerly known as Clostridium difficile, continues to be the most common healthcare-associated infection worldwide. With the shifting epidemiology towards higher a incidence of community-acquired CDI and the continued burden on the healthcare system posed by high rates of CDI recurrence, there has been an impetus to advance the diagnostic testing and treatment strategies. Recent advancements over the past decade have led to rapidly changing guidelines issued by the Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases. With our comprehensive review, we aim to summarize the latest advances in diagnosing and treating CDI and thus attempt to help readers guide best practices for patient care. This article also focusses on cost-effectiveness of various therapies currently available on the market and provides an analysis of the current evidence on a relatively new monoclonal antibody therapy, Bezlotoxumab, to treat recurrent CDI.}, }
@article {pmid33659796, year = {2020}, author = {Тикунов, &#x410;&#x42e; and Морозов, &#x412;&#x412; and Швалов, &#x410;&#x41d; and Бардашева, &#x410;&#x412; and Шрайнер, &#x415;&#x412; and Максимова, &#x41e;&#x410; and Волошина, &#x418;&#x41e; and Морозова, &#x412;&#x412; and Власов, &#x412;&#x412; and Тикунова, &#x41d;&#x412;}, title = {[Fecal microbiome change in patients with ulcerative colitis after fecal microbiota transplantation].}, journal = {Vavilovskii zhurnal genetiki i selektsii}, volume = {24}, number = {2}, pages = {168-175}, doi = {10.18699/VJ20.610}, pmid = {33659796}, issn = {2500-0462}, abstract = {Intestinal human microbiota is a dynamic system that is under the pressures of its host organism and external factors. Microbiota disruption caused by these factors can lead to severe diseases including inflammatory and oncological diseases of the gastrointestinal tract. One of the possible approaches in managing the intestinal microbiota is fecal microbiota transplantation (FT) - transfer of the microbiota from the stool of a healthy donor to the intestinal tract of a recipient patient. Currently, this procedure is recognized as an efficacious method to normalize the intestinal microbiota mainly in inflammatory diseases of the gastrointestinal tract. In Russia, pilot studies of the effectiveness of FT in patients with ulcerative colitis have been conducted for several years, and these studies were started in Novosibirsk. The aim of this study was to assess the change of intestinal microbiome in 20 patients with ulcerative colitis after a single FT procedure. The main method is a comparative analysis of 16S ribosomal RNA sequence libraries constructed using fecal samples obtained from patients with ulcerative colitis before and after FT and sequenced on the Illumina MiSeq platform. The obtained results showed that FT led to an increase in average biodiversity in samples after FT compared to samples before FT; however, the difference was not significant. In the samples studied, the proportion of Firmicutes sequences, the major gastrointestinal microbiota of healthy people, was decreased (~32 % vs. >70 %), while the proportion of Proteobacteria sequences was increased (>9 % vs. <5 %). In some samples collected before FT, sequences of pathogenic Firmicutes and Proteobacteria were detected, including Acinetobacter spp., Enterococcus spp., Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus, Stenotrophomonas maltophylia, Streptococcus spp. In most cases, the proportion of such sequences after FT substantially decreased in appropriate samples. The exception was the Clostridium difficile sequences, which accounted for <0.5 % of the sequences in samples from almost half of the patients and after FT, the share of such C. difficile sequences was significantly reduced only in samples from three patients. It should be noted that the proportion of Lactobacillus spp. increased ten-fold and their species composition significantly expanded. According to the obtained results, a preliminary conclusion can be made that even a single FT procedure can lead to an increase in the biodiversity of the gastrointestinal microbiota in patients and to the optimization of the taxonomic composition of the microbiota.}, }
@article {pmid33658399, year = {2021}, author = {Huang, J and Shan, W and Li, F and Wang, Z and Cheng, J and Lu, F and Guo, E and Beejadhursing, R and Xiao, R and Liu, C and Yang, B and Li, X and Fu, Y and Xi, L and Wang, S and Ma, D and Chen, G and Sun, C}, title = {Fecal microbiota transplantation mitigates vaginal atrophy in ovariectomized mice.}, journal = {Aging}, volume = {13}, number = {5}, pages = {7589-7607}, pmid = {33658399}, issn = {1945-4589}, mesh = {Animals ; Atrophy ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/genetics/physiology ; Mice ; Mice, Inbred C57BL ; Ovariectomy/*adverse effects ; RNA, Ribosomal, 16S/genetics ; Vagina/*pathology ; }, abstract = {Vulvovaginal atrophy (VVA) is a common menopause-related symptom affecting more than 50% of midlife and older women and cancer patients whose ovarian function are lost or damaged. Regardless of estrogen deficiency, whether other factors such as the gut microbiota play role in VVA have not been thoroughly investigated. To this end, we performed ovariectomy on 12-weeks' old mice and follow-up at 4 weeks after ovariectomy, and observed atrophied vagina and an altered gut microbiota in ovariectomized mice.. We further performed fecal microbiota transplantation with feces from another cohort of ovary-intact fecund female mice to the ovariectomized ones, and found that the vaginal epithelial atrophy was significantly alleviated as well as the gut microbiota was pointedly changed. All these results suggest that ovarian activity has some influence on the gut microbiota, and the latter from the ovary-intact female mice can somehow make the vagina of mice deficient in ovarian function healthier maybe by up-expressing ESR1 in vaginal cells and enhancing regeneration in vagina. This kind of association between gut microbiota and vaginal health need further exploration such that it may provide an alternative treatment by modulating gut microbiota in patients suffering from VVA but may be reluctant to hormone therapy.}, }
@article {pmid33655227, year = {2021}, author = {Quraishi, MN and Shabir, S and Manzoor, SE and Green, CA and Sharma, N and Beggs, AD and Iqbal, TH}, title = {The journey towards safely restarting faecal microbiota transplantation services in the UK during the COVID-19 era.}, journal = {The Lancet. Microbe}, volume = {2}, number = {4}, pages = {e133-e134}, pmid = {33655227}, issn = {2666-5247}, mesh = {*COVID-19 ; *Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Feces ; Humans ; United Kingdom/epidemiology ; }, }
@article {pmid33654104, year = {2021}, author = {Liao, C and Taylor, BP and Ceccarani, C and Fontana, E and Amoretti, LA and Wright, RJ and Gomes, ALC and Peled, JU and Taur, Y and Perales, MA and van den Brink, MRM and Littmann, E and Pamer, EG and Schluter, J and Xavier, JB}, title = {Compilation of longitudinal microbiota data and hospitalome from hematopoietic cell transplantation patients.}, journal = {Scientific data}, volume = {8}, number = {1}, pages = {71}, pmid = {33654104}, issn = {2052-4463}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U54 CA209975/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; }, mesh = {Feces/microbiology ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; *Hospitalization ; Humans ; RNA, Ribosomal, 16S/genetics ; United States ; }, abstract = {The impact of the gut microbiota in human health is affected by several factors including its composition, drug administrations, therapeutic interventions and underlying diseases. Unfortunately, many human microbiota datasets available publicly were collected to study the impact of single variables, and typically consist of outpatients in cross-sectional studies, have small sample numbers and/or lack metadata to account for confounders. These limitations can complicate reusing the data for questions outside their original focus. Here, we provide comprehensive longitudinal patient dataset that overcomes those limitations: a collection of fecal microbiota compositions (>10,000 microbiota samples from >1,000 patients) and a rich description of the "hospitalome" experienced by the hosts, i.e., their drug exposures and other metadata from patients with cancer, hospitalized to receive allogeneic hematopoietic cell transplantation (allo-HCT) at a large cancer center in the United States. We present five examples of how to apply these data to address clinical and scientific questions on host-associated microbial communities.}, }
@article {pmid33654015, year = {2021}, author = {Dalal, RS and Allegretti, JR}, title = {Diagnosis and management of Clostridioides difficile infection in patients with inflammatory bowel disease.}, journal = {Current opinion in gastroenterology}, volume = {37}, number = {4}, pages = {336-343}, pmid = {33654015}, issn = {1531-7056}, support = {T32 DK007533/DK/NIDDK NIH HHS/United States ; }, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Humans ; *Inflammatory Bowel Diseases/complications/diagnosis/therapy ; Neoplasm Recurrence, Local ; Prospective Studies ; Retrospective Studies ; }, abstract = {PURPOSE OF REVIEW: Clostridioides difficile infection (CDI) may complicate the course of ulcerative colitis and Crohn's disease. The clinical presentation of CDI in this population is often atypical, and patients may experience exacerbations of their underlying inflammatory bowel disease (IBD) secondary to C. difficile. In this review, we aim to review the risk factors, diagnosis, and management of CDI in the context of IBD.<br><br>RECENT FINDINGS: Patients with colonic involvement of their IBD are at higher risk for CDI and colonization may be more common than in the general population. Therefore, CDI is confirmed using a two-step approach to stool testing. Oral vancomycin or fidaxomicin are the preferred agents for nonfulminant disease, and oral metronidazole is no longer recommended as first-line therapy. For all patients with CDI recurrence, fecal microbiota transplant (FMT) should be considered, as this has been shown to be safe and effective. Among those who have worsening of their underlying IBD, retrospective research suggest that outcomes are improved for those who undergo escalation of immunosuppression with appropriate antimicrobial treatment of C. difficile, however prospective data are needed.<br><br>SUMMARY: CDI may complicate the course of IBD, however the presentation may not be typical. Therefore, all patients with worsening gastrointestinal symptoms should be evaluated for both CDI and IBD exacerbation. Providers should consider FMT for all patients with recurrent CDI as well as escalation of immunosuppression for patients who fail to improve with appropriate antimicrobial therapy.}, }
@article {pmid33653967, year = {2021}, author = {Grajeda-Iglesias, C and Durand, S and Daillère, R and Iribarren, K and Lemaitre, F and Derosa, L and Aprahamian, F and Bossut, N and Nirmalathasan, N and Madeo, F and Zitvogel, L and Kroemer, G}, title = {Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites.}, journal = {Aging}, volume = {13}, number = {5}, pages = {6375-6405}, pmid = {33653967}, issn = {1945-4589}, support = {P 27893/FWF_/Austrian Science Fund FWF/Austria ; P 29262/FWF_/Austrian Science Fund FWF/Austria ; W 1226/FWF_/Austrian Science Fund FWF/Austria ; P 31727/FWF_/Austrian Science Fund FWF/Austria ; P 29203/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Administration, Oral ; Akkermansia ; Animals ; Fatty Acids, Volatile/metabolism ; Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism ; Hydroxybutyrates/metabolism ; Liver/metabolism ; Metabolome ; Metabolomics ; Mice, Inbred C57BL ; Pasteurization ; Polyamines/metabolism ; Probiotics/*pharmacology ; Spermidine/metabolism ; Mice ; }, abstract = {The presence of Akkermansia muciniphila (Akk) in the human gut is associated with good health, leanness and fitness. Mouse experimentation has demonstrated positive effects for Akk, which counteracts aging, mediates antiobesity and antidiabetic effects, dampens inflammation and improves anticancer immunosurveillance. Clinical trials have confirmed antidiabetic effects for Akk. Here, we investigated the time-dependent effects of oral administration of Akk (which was live or pasteurized) and other bacteria to mice on the metabolome of the ileum, colon, liver and blood plasma. Metabolomics was performed by a combination of chromatographic and mass spectrometric methods, yielding a total of 1.637.227 measurements. Akk had major effects on metabolism, causing an increase in spermidine and other polyamines in the gut and in the liver. Pasteurized Akk (Akk-past) was more efficient than live Akk in elevating the intestinal concentrations of polyamines, short-chain fatty acids, 2-hydroxybutyrate, as well multiple bile acids, which also increased in the circulation. All these metabolites have previously been associated with human health, providing a biochemical basis for the beneficial effects of Akk.}, }
@article {pmid33652903, year = {2021}, author = {Khor, B and Snow, M and Herrman, E and Ray, N and Mansukhani, K and Patel, KA and Said-Al-Naief, N and Maier, T and Machida, CA}, title = {Interconnections Between the Oral and Gut Microbiomes: Reversal of Microbial Dysbiosis and the Balance Between Systemic Health and Disease.}, journal = {Microorganisms}, volume = {9}, number = {3}, pages = {}, pmid = {33652903}, issn = {2076-2607}, abstract = {The human microbiota represents a complex array of microbial species that influence the balance between the health and pathology of their surrounding environment. These microorganisms impart important biological benefits to their host, such as immune regulation and resistance to pathogen colonization. Dysbiosis of microbial communities in the gut and mouth precede many oral and systemic diseases such as cancer, autoimmune-related conditions, and inflammatory states, and can involve the breakdown of innate barriers, immune dysregulation, pro-inflammatory signaling, and molecular mimicry. Emerging evidence suggests that periodontitis-associated pathogens can translocate to distant sites to elicit severe local and systemic pathologies, which necessitates research into future therapies. Fecal microbiota transplantation, probiotics, prebiotics, and synbiotics represent current modes of treatment to reverse microbial dysbiosis through the introduction of health-related bacterial species and substrates. Furthermore, the emerging field of precision medicine has been shown to be an effective method in modulating host immune response through targeting molecular biomarkers and inflammatory mediators. Although connections between the human microbiome, immune system, and systemic disease are becoming more apparent, the complex interplay and future innovations in treatment modalities will become elucidated through continued research and cross-disciplinary collaboration.}, }
@article {pmid33652261, year = {2021}, author = {Yang, S and Hu, T and Liu, H and Lv, YL and Zhang, W and Li, H and Xuan, L and Gong, LL and Liu, LH}, title = {Akebia saponin D ameliorates metabolic syndrome (MetS) via remodeling gut microbiota and attenuating intestinal barrier injury.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {138}, number = {}, pages = {111441}, doi = {10.1016/j.biopha.2021.111441}, pmid = {33652261}, issn = {1950-6007}, mesh = {Animals ; Cell Line ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Intestinal Mucosa/*drug effects/metabolism/pathology ; Male ; Metabolic Syndrome/*drug therapy/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Saponins/pharmacology/*therapeutic use ; }, abstract = {Metabolic syndrome (MetS) is a complex, multifactorial disease which lead to an increased risk of cardiovascular disease, type 2 diabetes, and stroke. However, selective, and potent drugs for the treatment of MetS are still lacking. Previous studies have found that Akebia saponin D (ASD) has beneficial effects on metabolic diseases such as obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Therefore, our study was designed to determine the effect and mechanism of action of ASD against MetS in a high-fat diet (HFD) induced mouse model. ASD significantly decreased plasma lipid and insulin resistance in these mice, and a targeted approach using metabolomic analyses of plasma and feces indicated that glucose and lipids in these mice crossed the damaged intestinal barrier into circulation. Furthermore, ASD was able to increase lipid excretion and inhibit intestinal epithelial lipid absorption. Results for gut microbiota composition showed that ASD significantly reduced HFD-associated Alistipes, Prevotella, and enhanced the proportions of Butyricimonas, Ruminococcus, and Bifidobacterium. After 14 weeks of ASD/fecal microbiota transplantation (FMT) interventions the developed gut barrier dysfunction was restored. Additionally, RNA-seq revealed that ASD reduced the lipid-induced tight junction (TJ) damage in intestinal epithelial cells via down-regulation of the PPAR-γ-FABP4 pathway in vitro and that use of the PPAR-γ inhibitor (T0070907) was able to partially block the effects of ASD, indicating that the PPAR-γ/FABP4 pathway is a critical mediator involved in the improvement of MetS. Our results demonstrated that ASD not only modifies the gut microbiome but also ameliorates the HFD-induced gut barrier disruption via down-regulation of the PPAR-γ-FABP4 pathway. These findings suggest a promising, and novel therapeutic strategy for gut protection against MetS.}, }
@article {pmid33651981, year = {2021}, author = {Liu, X and Li, X and Xia, B and Jin, X and Zou, Q and Zeng, Z and Zhao, W and Yan, S and Li, L and Yuan, S and Zhao, S and Dai, X and Yin, F and Cadenas, E and Liu, RH and Zhao, B and Hou, M and Liu, Z and Liu, X}, title = {High-fiber diet mitigates maternal obesity-induced cognitive and social dysfunction in the offspring via gut-brain axis.}, journal = {Cell metabolism}, volume = {33}, number = {5}, pages = {923-938.e6}, doi = {10.1016/j.cmet.2021.02.002}, pmid = {33651981}, issn = {1932-7420}, mesh = {Adolescent ; Animals ; Behavior, Animal/*drug effects ; Brain-Gut Axis/*physiology ; Child ; Cognition/*drug effects ; Cross-Sectional Studies ; Dietary Fiber/*pharmacology ; Fatty Acids, Volatile/pharmacology ; Female ; Gastrointestinal Microbiome/drug effects ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Pregnancy in Obesity/*pathology ; Pregnancy ; *Social Behavior ; Spliceosomes/metabolism ; Synapses/drug effects/metabolism ; }, abstract = {Maternal obesity has been reported to be related to neurodevelopmental disorders in the offspring. However, the underlying mechanisms and effective interventions remain unclear. This cross-sectional study with 778 children aged 7-14 years in China indicated that maternal obesity is strongly associated with children's lower cognition and sociality. Moreover, it has been demonstrated that maternal obesity in mice disrupted the behavior and gut microbiome in offspring, both of which were restored by a high-fiber diet in either dams or offspring via alleviating synaptic impairments and microglial maturation defects. Co-housing and feces microbiota transplantation experiments revealed a causal relationship between microbiota and behavioral changes. Moreover, treatment with the microbiota-derived short-chain fatty acids also alleviated the behavioral deficits in the offspring of obese dams. Together, our study indicated that the microbiota-metabolites-brain axis may underlie maternal obesity-induced cognitive and social dysfunctions and that high dietary fiber intake could be a promising intervention.}, }
@article {pmid33651137, year = {2021}, author = {Ghorbani, Y and Schwenger, KJP and Allard, JP}, title = {Manipulation of intestinal microbiome as potential treatment for insulin resistance and type 2 diabetes.}, journal = {European journal of nutrition}, volume = {60}, number = {5}, pages = {2361-2379}, pmid = {33651137}, issn = {1436-6215}, mesh = {*Diabetes Mellitus, Type 2/therapy ; *Gastrointestinal Microbiome ; Humans ; *Insulin Resistance ; Prebiotics ; *Probiotics ; *Synbiotics ; }, abstract = {PURPOSE: Increasing evidence suggests that the intestinal microbiome (IM) and bacterial metabolites may influence glucose homeostasis, energy expenditure and the intestinal barrier integrity and lead to the presence of systemic low-grade inflammation, all of which can contribute to insulin resistance (IR) and type 2 diabetes (T2D). The purpose of this review is to explore the role of the IM and bacterial metabolites in the pathogenesis and treatment of these conditions.<br><br>RESULTS: This review summarizes research focused on how to modulate the IM through diet, prebiotics, probiotics, synbiotics and fecal microbiota transplant in order to treat IR and T2D.<br><br>CONCLUSION: There is an abundance of evidence suggesting a role for IM in the pathogenesis of IR and T2D based on reviewed studies using various methods to modulate IM and metabolites. However, the results are inconsistent. Future research should further assess this relationship.}, }
@article {pmid33644835, year = {2021}, author = {Wu, C and Shang, H and Jiang, X and Wang, X and Wei, H}, title = {Application of germ-free NOD-scid IL2rg[null] mice as a humanized model for tumor microbiome precision medicine.}, journal = {Science China. Life sciences}, volume = {64}, number = {4}, pages = {644-647}, pmid = {33644835}, issn = {1869-1889}, mesh = {Animals ; *Disease Models, Animal ; Fecal Microbiota Transplantation/methods ; Germ-Free Life/*immunology ; Humans ; Immunotherapy/methods ; Interleukin Receptor Common gamma Subunit/deficiency/genetics/*immunology ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Mice, Transgenic ; Microbiota/*immunology ; Neoplasms/*immunology/microbiology/therapy ; Precision Medicine/*methods ; }, }
@article {pmid33643302, year = {2020}, author = {Liu, Y and Li, Z and Wu, Y and Jing, X and Li, L and Fang, X}, title = {Intestinal Bacteria Encapsulated by Biomaterials Enhance Immunotherapy.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {620170}, pmid = {33643302}, issn = {1664-3224}, mesh = {Administration, Oral ; Animals ; Antigen-Presenting Cells/immunology ; B-Lymphocytes/immunology ; Biocompatible Materials/*administration &amp; dosage ; *Cell Encapsulation ; DNA, Bacterial/administration &amp; dosage ; Drug Carriers/administration &amp; dosage ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/immunology/physiology ; Humans ; Immunotherapy/*methods ; Injections, Intravenous ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Probiotics/administration &amp; dosage ; T-Lymphocyte Subsets/immunology ; }, abstract = {The human intestine contains thousands of bacterial species essential for optimal health. Aside from their pathogenic effects, these bacteria have been associated with the efficacy of various treatments of diseases. Due to their impact on many human diseases, intestinal bacteria are receiving increasing research attention, and recent studies on intestinal bacteria and their effects on treatments has yielded valuable results. Particularly, intestinal bacteria can affect responses to numerous forms of immunotherapy, especially cancer therapy. With the development of precision medicine, understanding the factors that influence intestinal bacteria and how they can be regulated to enhance immunotherapy effects will improve the application prospects of intestinal bacteria therapy. Further, biomaterials employed for the convenient and efficient delivery of intestinal bacteria to the body have also become a research hotspot. In this review, we discuss the recent findings on the regulatory role of intestinal bacteria in immunotherapy, focusing on immune cells they regulate. We also summarize biomaterials used for their delivery.}, }
@article {pmid33642013, year = {2021}, author = {Han, B and Jiang, P and Jiang, L and Li, X and Ye, X}, title = {Three phytosterols from sweet potato inhibit MCF7-xenograft-tumor growth through modulating gut microbiota homeostasis and SCFAs secretion.}, journal = {Food research international (Ottawa, Ont.)}, volume = {141}, number = {}, pages = {110147}, doi = {10.1016/j.foodres.2021.110147}, pmid = {33642013}, issn = {1873-7145}, mesh = {Animals ; Breast Neoplasms ; Female ; *Gastrointestinal Microbiome ; Heterografts ; Homeostasis ; Humans ; *Ipomoea batatas ; MCF-7 Cells ; Mice ; Mice, Nude ; Phosphatidylinositol 3-Kinases ; *Phytosterols ; Xenograft Model Antitumor Assays ; }, abstract = {Researches demonstrated that gut microbiota are associated with breast cancer progression. This study aims to evaluate the anti-breast tumor effects of daucosterol linolenate (DLA), daucosterol linoleate (DL), and daucosterol palmitate (DP) from sweet potato in MCF-7 xenograft nude mice by determining the tumor growth, serum tumor markers, tumor-related proteins, and performing 16S rDNA sequencing. After treatment at 87.8 mg/kg/day for 29 days, DLA, DL and DP delayed tumor growth and decreased levels of tumor marker carcinoembryonic antigen (CEA), cancer antigen 125 (CA125) and cancer antigen 153 (CA153) in vivo. All treatments activated caspase 3, 9, PARP1 cleavage, down-regulated Ki67, VEGF, BCL-2, BCL-XL, up-regulated BAX expression, and inhibited PI3K/AKT/NF-κB activation in tumor tissues. Their anti-breast tumor effects were associated with the regulation on gut microbiota. The three treatments increased Bacteroidetes whereas decreased Firmicutes richness. They also modulated the diversity of gut microbiota at family and genus levels. Furthermore, DL treatment promoted butyric acid secretion, DP promoted acetic acid and butyric acid secretion in the colorectal and feces. Our findings indicate that DLA, DL, and DP inhibit tumor growth in MCF-7 xenograft nude mice by regulating the homeostasis of gut microbiota, producing SCFAs, and then disturbing the expression of cancer-related proteins. The present study suggests three phytosterols as gut microbiota regulator for breast cancer prevention.}, }
@article {pmid33639935, year = {2021}, author = {Al-Bakri, AG and Akour, AA and Al-Delaimy, WK}, title = {Knowledge, attitudes, ethical and social perspectives towards fecal microbiota transplantation (FMT) among Jordanian healthcare providers.}, journal = {BMC medical ethics}, volume = {22}, number = {1}, pages = {19}, pmid = {33639935}, issn = {1472-6939}, support = {R25 TW010026/TW/FIC NIH HHS/United States ; 5R25TW010026-02/TW/FIC NIH HHS/United States ; }, mesh = {Cross-Sectional Studies ; *Fecal Microbiota Transplantation/ethics ; Feces ; *Health Knowledge, Attitudes, Practice ; Humans ; Microbiota ; }, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) is a treatment modality that involves the introduction of stool from a healthy pre-screened donor into the gastrointestinal tract of a patient. It exerts its therapeutic effects by remodeling the gut microbiota and treating microbial dysbiosis-imbalance. FMT is not regulated in Jordan, and regulatory effort for FMT therapy in Jordan, an Islamic conservative country, might be faced with unique cultural, social, religious, and ethical challenges. We aimed to assess knowledge, attitudes, and perceptions of ethical and social issues of FMT use among Jordanian healthcare professionals.<br><br>METHODS: An observational, cross-sectional study design was used to assess knowledge, attitudes, and perceptions of ethical and social issues of FMT among 300 Jordanian healthcare professionals.<br><br>RESULTS: A large proportion (39&#x2009;%) thought that the safety and efficacy of this technique are limited and 29.3&#x2009;% thought there is no evidence to support its use. Almost all (95&#x2009;%) responded that they would only perform it in certain cases, if ethically justified, and 48.3&#x2009;% would use it due to treatment failure of other approaches. When reporting about reasons for not using it, 40&#x2009;% reported that they would not perform it due to concerns about medical litigation, fear of infections (38&#x2009;%), and lack of knowledge of long safety and efficacy (31.3&#x2009;%). Interestingly, all practitioners said they would perform this procedure through the lower rather than upper gastrointestinal tract modality and the majority will protect the patient's confidentiality via double-blinding (43.3&#x2009;%). For a subset of participants (n&#x2009;=&#x2009;100), the cultural constraints that might affect the choice of performing FMT were mainly due to donor's religion, followed by dietary intake, and alcohol consumption.<br><br>CONCLUSIONS: Our healthcare practitioners are generally reluctant to use the FMT modality due to religious and ethical reasons but would consider it if there was a failure of other treatment and after taking into consideration many legislative, social, ethical and practice-based challenges including safety, efficacy and absence of guidelines.}, }
@article {pmid33639698, year = {2021}, author = {Afecto, E and Ponte, A and Fernandes, S and Silva, J and Gomes, C and Correia, J and Carvalho, J}, title = {Fecal microbiota transplantation in hepatic encephalopathy : a review of the current evidence and future perspectives.}, journal = {Acta gastro-enterologica Belgica}, volume = {84}, number = {1}, pages = {87-90}, doi = {10.51821/84.1.884}, pmid = {33639698}, issn = {1784-3227}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; *Hepatic Encephalopathy/therapy ; Humans ; Liver Cirrhosis ; }, abstract = {Hepatic encephalopathy (HE) is a leading cause of hospitalization and morbimortality in advanced cirrhosis with limited therapeutic options available. Given the paramount role of gut microbiota in HE, and the efficacy of fecal microbiota transplantation (FMT) in other diseases, this review intends to summarize the evidence supporting the safety, efficacy and future perspectives of FMT in HE. Current evidence, despite being scarce, points towards FMT being a safe, effective and tolerable procedure in HE. Some unanswered questions remain about the optimal dose, the administration route, the long term effects and the selection of the optimal donor. Future trials, some of which are already underway, will provide us additional evidence and hopefully the necessary answers.}, }
@article {pmid33633264, year = {2021}, author = {Staley, C and Halaweish, H and Graiziger, C and Hamilton, MJ and Kabage, AJ and Galdys, AL and Vaughn, BP and Vantanasiri, K and Suryanarayanan, R and Sadowsky, MJ and Khoruts, A}, title = {Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4519}, pmid = {33633264}, issn = {2045-2322}, mesh = {Aged ; Aged, 80 and over ; Biodiversity ; Clostridium Infections/*microbiology/*therapy ; Disease Management ; Disease Susceptibility ; Fecal Microbiota Transplantation/*methods ; Female ; Freeze Drying ; Gastrointestinal Microbiome ; Humans ; Male ; Metagenome ; Metagenomics/methods ; Middle Aged ; Transanal Endoscopic Microsurgery/*methods ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (rCDI). However, standardization of FMT products is essential for its broad implementation into clinical practice. We have developed an oral preparation of freeze-dried, encapsulated microbiota, which is ~ 80% clinically effective, but results in delayed engraftment of donor bacteria relative to administration via colonoscopy. Our objective was to measure the engraftment potential of freeze-dried microbiota without the complexity of variables associated with oral administration. We compared engraftment of identical preparations and doses of freeze-dried microbiota following colonoscopic (9 patients) versus oral administration (18 patients). Microbiota were characterized by sequencing of the 16S rRNA gene, and engraftment was determined using the SourceTracker algorithm. Oligotyping analysis was done to provide high-resolution patterns of microbiota engraftment. Colonoscopic FMT was associated with greater levels of donor engraftment within days following the procedure (ANOVA P = 0.035) and specific increases in the relative abundances of donor Lachnospiraceae, Bacteroidaceae, and Porphyromonadaceae (P ≤ 0.033). Lower relative abundances of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae families were associated with clinical failures. These results suggest that further optimization of oral capsule FMT may improve its engraftment efficiency and clinical efficacy.}, }
@article {pmid33633259, year = {2021}, author = {Sasaki, K and Sasaki, D and Sasaki, K and Nishidono, Y and Yamamori, A and Tanaka, K and Kondo, A}, title = {Growth stimulation of Bifidobacterium from human colon using daikenchuto in an in vitro model of human intestinal microbiota.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4580}, pmid = {33633259}, issn = {2045-2322}, mesh = {Bifidobacterium/*drug effects/growth &amp; development/isolation &amp; purification ; Colon/*microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Humans ; In Vitro Techniques ; Panax ; Plant Extracts/*pharmacology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA/methods ; Zanthoxylum ; Zingiberaceae ; }, abstract = {Daikenchuto (DKT) is a Japanese traditional herbal (Kampo) medicine containing ginseng, processed ginger, and Japanese or Chinese pepper. We aimed to determine how DKT affects human colonic microbiota. An in vitro microbiota model was established using fecal inocula collected from nine healthy volunteers, and each model was found to retain operational taxonomic units similar to the ones in the original human fecal samples. DKT was added to the in vitro microbiota model culture at a concentration of 0.5% by weight. Next-generation sequencing of bacterial 16S rRNA gene revealed a significant increase in the relative abundance of bacteria related to the Bifidobacterium genus in the model after incubation with DKT. In pure cultures, DKT significantly promoted the growth of Bifidobacterium adolescentis, but not that of Fusobacterium nucleatum or Escherichia coli. Additionally, in pure cultures, B. adolescentis transformed ginsenoside Rc to Rd, which was then probably utilized for its growth. Our study reveals the in vitro bifidogenic effect of DKT that likely contributes to its beneficial effects on the human colon.}, }
@article {pmid33631870, year = {2021}, author = {Arregui Garcia, I and Elía Lòpez, M and Aguinaga Pérez, A and Manrique Escola, J and Ezpeleta Baquedano, C}, title = {[Cryptosporidiosis in immunosuppressed renal transplant patient].}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {34}, number = {2}, pages = {164-166}, pmid = {33631870}, issn = {1988-9518}, mesh = {*Cryptosporidiosis/drug therapy ; Feces ; Humans ; Immunocompromised Host ; *Kidney Transplantation ; }, }
@article {pmid33631102, year = {2021}, author = {Kao, D and Wong, K and Franz, R and Cochrane, K and Sherriff, K and Chui, L and Lloyd, C and Roach, B and Bai, AD and Petrof, EO and Allen-Vercoe, E}, title = {The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {6}, number = {4}, pages = {282-291}, doi = {10.1016/S2468-1253(21)00007-8}, pmid = {33631102}, issn = {2468-1253}, mesh = {Aged ; Clostridium Infections/*therapy ; Disease-Free Survival ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection but has inherent risks. Microbial Ecosystem Therapeutic 2 (MET-2) is an oral encapsulated formulation of 40 lyophilised bacterial species initially isolated from stool of a healthy donor, but subsequently manufactured independently of donors, eliminating potential risks introduced by changes in donor health. The aim of this study was to determine MET-2 activity, safety, and tolerability.<br><br>METHODS: This phase 1, open-label, single-group feasibility study was done in Alberta, Canada. The main inclusion criteria were mild to moderate C difficile infection and at least one episode of C difficile infection recurrence (ie, two episodes of C difficile infection) within 12 months. Initial daily treatment was ten oral capsules for 2 days, then three capsules for 8 days. If C difficile infection recurred, a higher dose was offered: 20 capsules for 2 days, then three capsules for 8 days. Patients were followed for adverse events and C difficile infection recurrence up to day 130. The primary outcome was absence of C difficile infection recurrence (fewer than three unformed bowel movements in 24 h persisting for at least 2 days) at day 40 by intention-to-treat analysis. Secondary outcomes were mortality or hospitalisation due to C difficile infection, infections attributed to treatment, nausea, abdominal pain, vomiting, or diarrhoea during treatment, quality of life (C difficile Health Related Quality of Life Questionnaire) before and after treatment, and engrafted MET-2 bacteria in patient stool. Absence of C difficile infection recurrence at day 130 was an exploratory outcome. This study is registered with ClinicalTrials.gov, NCT02865616 FINDINGS: Between Sept 19, 2018, and Feb 28, 2020, we enrolled 19 adult patients with at least two episodes of mild to moderate C difficile infection (median age 65 years [IQR 56-67]; 12 women [63%], seven men [37%]). Recurrent C difficile infection was absent at day 40 in 15 (79%) of 19 patients after initial treatment, increasing to 18 (95%) 40 days after retreatment. No mortality associated with C difficile infection, infections associated with MET-2 treatment, or other serious adverse events were observed. The most common self-limited, mild to moderate symptoms reported during treatment were diarrhoea in 12 (63%) of 19 patients and abdominal cramps in 12 (63%). After MET-2 treatment, quality of life improved significantly, as did alpha diversity in stool microbial composition (p=1&#xb7;93&#xd7;10[-6]). MET-2 associated taxa were found in greater abundance in most patients after treatment compared with baseline. 16 (84%) of 19 patients did not have recurrence of C difficile infection by day 130.<br><br>INTERPRETATION: MET-2 appears to be safe, efficacious, and well tolerated among patients with recurrent C difficile infection. Results must be validated in controlled studies.<br><br>FUNDING: NuBiyota.}, }
@article {pmid33628361, year = {2021}, author = {Du, D and Tang, W and Zhou, C and Sun, X and Wei, Z and Zhong, J and Huang, Z}, title = {Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury.}, journal = {Oxidative medicine and cellular longevity}, volume = {2021}, number = {}, pages = {5816837}, pmid = {33628361}, issn = {1942-0994}, mesh = {Animals ; Brain/*pathology ; Brain Injuries, Traumatic/blood/*microbiology/*therapy ; Dysbiosis/blood/*complications/*microbiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Hippocampus/pathology ; Male ; Metabolome ; Methylamines/metabolism ; Oxidative Stress ; Oxidoreductases/metabolism ; Proteomics ; Rats, Sprague-Dawley ; Rats ; }, abstract = {BACKGROUND: Traumatic brain injury (TBI) can induce persistent fluctuation in the gut microbiota makeup and abundance. The present study is aimed at determining whether fecal microbiota transplantation (FMT) can rescue microbiota changes and ameliorate neurological deficits after TBI in rats.<br><br>METHODS: A controlled cortical impact (CCI) model was used to simulate TBI in male Sprague-Dawley rats, and FMT was performed for 7 consecutive days. 16S ribosomal RNA (rRNA) sequencing of fecal samples was performed to analyze the effects of FMT on gut microbiota. Modified neurological severity score and Morris water maze were used to evaluate neurobehavioral functions. Metabolomics was used to screen differential metabolites from the rat serum and ipsilateral brains. The oxidative stress indices were measured in the brain.<br><br>RESULTS: TBI induced significance changes in the gut microbiome, including the alpha- and beta-bacterial diversity, as well as the microbiome composition at 8 days after TBI. On the other hand, FMT could rescue these changes and relieve neurological deficits after TBI. Metabolomics results showed that the level of trimethylamine (TMA) in feces and the level of trimethylamine N-oxide (TMAO) in the ipsilateral brain and serum was increased after TBI, while FMT decreased TMA levels in the feces, and TMAO levels in the ipsilateral brain and serum. Antioxidant enzyme methionine sulfoxide reductase A (MsrA) in the ipsilateral hippocampus was decreased after TBI but increased after FMT. In addition, FMT elevated SOD and CAT activities and GSH/GSSG ratio and diminished ROS, GSSG, and MDA levels in the ipsilateral hippocampus after TBI.<br><br>CONCLUSIONS: FMT can restore gut microbiota dysbiosis and relieve neurological deficits possibly through the TMA-TMAO-MsrA signaling pathway after TBI.}, }
@article {pmid33625548, year = {2021}, author = {Wang, J and Li, X and Wu, X and Wang, Z and Zhang, C and Cao, G and Liu, S and Yan, T}, title = {Gut microbiota alterations associated with antibody-mediated rejection after kidney transplantation.}, journal = {Applied microbiology and biotechnology}, volume = {105}, number = {6}, pages = {2473-2484}, pmid = {33625548}, issn = {1432-0614}, support = {No. 32000650//National Natural Science Foundation of China/ ; No. 192102310036//Henan Provincial Scientific and Technological Research Project/ ; No. 201702191//Henan Provincial Medical Scientific and Technological Research Project/ ; }, mesh = {*Gastrointestinal Microbiome ; Humans ; Kidney ; *Kidney Transplantation/adverse effects ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Antibody-mediated rejection (AMR) has become the major challenge for kidney transplantation, and the efficacy of existing therapies was limited to prevent AMR. Increasing evidences have demonstrated the link between gut microbiota alterations and allograft outcome. However, there has been no comprehensive analysis to profile the gut microbiota associated with AMR after kidney transplantation. We performed this study to characterize the gut microbiota possibly associated with AMR. Fecal specimens were collected from 24 kidney transplantation recipients with AMR and 29 controls. DNA extracted from the specimens was processed for 16S rRNA gene sequencing using Illumina MiSeq. Gut microbial community of recipients with AMR was significantly different from that of controls based on unweighted (P = 0.001) and weighted (P = 0.02) UniFrac distances, and the bacterial richness (observed species: P = 0.0448; Chao1 index: P = 0.0450; ACE index: P = 0.0331) significantly decreased in the AMR group. LEfSe showed that 1 phylum, 5 classes, 7 families, and 10 genera were increased, whereas 1 class, 2 order, 3 families, and 4 genera were decreased in the AMR group. Specific taxa such as Clostridiales could be potentially used as biomarkers to distinguish the recipients with AMR from the controls (AUC = 0.77). PICRUSt analysis illustrated that 16 functional pathways were with significantly different abundances in the AMR and control groups. Our findings provide a foundation for further investigation on the role of gut microbiota in AMR after kidney transplantation, and potentially support novel diagnostic biomarkers and therapeutic options for AMR. KEY POINTS: • Gut microbial community of kidney recipients with AMR was different from that of controls. • Clostridiales is a potential marker to distinguish recipients with AMR from controls.}, }
@article {pmid33623056, year = {2021}, author = {Berland, M and Cadiou, J and Levenez, F and Galleron, N and Quinquis, B and Thirion, F and Gauthier, F and Le Chatelier, E and Plaza Oñate, F and Schwintner, C and Rabot, S and Lepage, P and Ehrlich, D and Doré, J and Juste, C}, title = {High engraftment capacity of frozen ready-to-use human fecal microbiota transplants assessed in germ-free mice.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4365}, pmid = {33623056}, issn = {2045-2322}, mesh = {Animals ; Cryopreservation/methods ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Male ; Metagenomics/methods ; Mice ; Mice, Inbred C57BL ; }, abstract = {The number of indications for fecal microbiota transplantation is expected to rise, thus increasing the needs for production of readily available frozen or freeze-dried transplants. Using shotgun metagenomics, we investigated the capacity of two novel human fecal microbiota transplants prepared in maltodextrin-trehalose solutions (abbreviated MD and TR for maltodextrin:trehalose, 3:1, w/w, and trehalose:maltodextrin 3:1, w/w, respectively), to colonize a germ-free born mouse model. Gavage with frozen-thawed MD or TR suspensions gave the taxonomic profiles of mouse feces that best resembled those obtained with the fresh inoculum (Spearman correlations based on relative abundances of metagenomic species around 0.80 and 0.75 for MD and TR respectively), while engraftment capacity of defrosted NaCl transplants most diverged (Spearman correlations around 0.63). Engraftment of members of the family Lachnospiraceae and Ruminoccocaceae was the most challenging in all groups of mice, being improved with MD and TR transplants compared to NaCl, but still lower than with the fresh preparation. Improvement of engraftment of this important group in maintaining health represents a challenge that could benefit from further research on fecal microbiota transplant manufacturing.}, }
@article {pmid33623004, year = {2021}, author = {Wang, Y and Tong, Q and Ma, SR and Zhao, ZX and Pan, LB and Cong, L and Han, P and Peng, R and Yu, H and Lin, Y and Gao, TL and Shou, JW and Li, XY and Zhang, XF and Zhang, ZW and Fu, J and Wen, BY and Yu, JB and Cao, X and Jiang, JD}, title = {Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson's disease by regulating gut microbiota.}, journal = {Signal transduction and targeted therapy}, volume = {6}, number = {1}, pages = {77}, pmid = {33623004}, issn = {2059-3635}, mesh = {Animals ; Berberine/analogs &amp; derivatives/*pharmacology ; Corpus Striatum/drug effects/microbiology ; Dihydroxyphenylalanine/*metabolism ; Dopamine/metabolism ; Enterococcus faecalis/metabolism ; Enterococcus faecium/metabolism ; Gastrointestinal Microbiome/*drug effects ; Humans ; Levodopa/metabolism ; Mice ; Parkinson Disease/*drug therapy/metabolism/microbiology ; Tyrosine 3-Monooxygenase/genetics ; }, abstract = {The phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa (L-dopa) with tetrahydrobiopterin (BH4) as a coenzyme. Here, we show that oral berberine (BBR) might supply H[•] through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH4 from dihydrobiopterin; the increased BH4 enhances TH activity, which accelerates the production of L-dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The L-dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut-brain dialog activated by BBR's effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson's disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus, and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of L-dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal L-dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of L-dopa in the gut microbiota through a vitamin-like effect.}, }
@article {pmid33622223, year = {2021}, author = {Menzel, K and Kothare, P and McCrea, JB and Chu, X and Kropeit, D}, title = {Absorption, Metabolism, Distribution, and Excretion of Letermovir.}, journal = {Current drug metabolism}, volume = {22}, number = {10}, pages = {784-794}, doi = {10.2174/1389200222666210223112826}, pmid = {33622223}, issn = {1875-5453}, mesh = {ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism ; *Acetates/metabolism/pharmacokinetics ; Adult ; Animals ; Antiviral Agents/metabolism/pharmacokinetics ; *Biotransformation ; Cytochrome P-450 CYP3A/metabolism ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/*drug therapy ; Drug Elimination Routes/*physiology ; *Drug Interactions ; Glucuronosyltransferase/metabolism ; Healthy Volunteers ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Male ; Medication Therapy Management/standards ; Neoplasm Proteins/metabolism ; Organic Anion Transporters/metabolism ; *Quinazolines/metabolism/pharmacokinetics ; Rats ; Tissue Distribution/*physiology ; }, abstract = {BACKGROUND: Letermovir is approved for prophylaxis of cytomegalovirus infection and disease in cytomegalovirus-seropositive hematopoietic stem-cell transplant (HSCT) recipients.<br><br>OBJECTIVE: HSCT recipients are required to take many drugs concomitantly. The pharmacokinetics, absorption, distribution, metabolism, and excretion of letermovir and its potential to inhibit metabolizing enzymes and transporters in vitro were investigated to inform on the potential for drug-drug interactions (DDIs).<br><br>METHODS: A combination of in vitro and in vivo studies described the absorption, distribution, metabolism, and routes of elimination of letermovir, as well as the enzymes and transporters involved in these processes. The effect of letermovir to inhibit and induce metabolizing enzymes and transporters was evaluated in vitro and its victim and perpetrator DDI potentials were predicted by applying the regulatory guidance for DDI assessment.<br><br>RESULTS: Letermovir was a substrate of CYP3A4/5 and UGT1A1/3 in vitro. Letermovir showed concentration- dependent uptake into organic anionic transporting polypeptide (OATP)1B1/3-transfected cells and was a substrate of P-glycoprotein (P-gp). In a human ADME study, letermovir was primarily recovered as unchanged drug and minor amounts of a direct glucuronide in feces. Based on the metabolic pathway profiling of letermovir, there were few oxidative metabolites in human matrix. Letermovir inhibited CYP2B6, CYP2C8, CYP3A, and UGT1A1 in vitro, and induced CYP3A4 and CYP2B6 in hepatocytes. Letermovir also inhibited OATP1B1/3, OATP2B1, OAT3, OCT2, BCRP, BSEP, and P-gp.<br><br>CONCLUSION: The body of work presented in this manuscript informed on the potential for DDIs when letermovir is administered both intravenously and orally in HSCT recipients.}, }
@article {pmid33621544, year = {2021}, author = {Pennesi, CM and English, EM and Bell, S and Lossie, AC and Quint, EH and Swenson, CW}, title = {Prevalence of urinary, prolapse, and bowel symptoms in Mayer-Rokitansky-Küster-Hauser syndrome.}, journal = {American journal of obstetrics and gynecology}, volume = {225}, number = {1}, pages = {70.e1-70.e12}, doi = {10.1016/j.ajog.2021.02.020}, pmid = {33621544}, issn = {1097-6868}, support = {K12 HD065257/HD/NICHD NIH HHS/United States ; }, mesh = {46, XX Disorders of Sex Development/*epidemiology/*surgery ; Adult ; Congenital Abnormalities/*epidemiology/*surgery ; Constipation/epidemiology ; Cross-Sectional Studies ; Fecal Incontinence/*epidemiology ; Female ; Gynecologic Surgical Procedures/methods ; Humans ; Mullerian Ducts/*abnormalities/surgery ; Pelvic Floor Disorders/*epidemiology ; Pelvic Organ Prolapse/*epidemiology ; Quality of Life ; Surveys and Questionnaires ; Urinary Tract Infections/epidemiology ; Urination Disorders/epidemiology ; Urologic Diseases/*epidemiology ; Vagina/surgery ; }, abstract = {BACKGROUND: Müllerian agenesis, or Mayer-Rokitansky-Küster-Hauser syndrome, occurs in 1 in 4500 to 5000 individuals assigned female sex at birth. Pelvic floor symptoms among individuals with Mayer-Rokitansky-Küster-Hauser syndrome have not been well studied, and it is unknown how vaginal lengthening treatments affect these symptoms.<br><br>OBJECTIVE: This study aimed to assess urinary, prolapse, and bowel symptoms in individuals with Mayer-Rokitansky-K&#xfc;ster-Hauser syndrome and to determine whether symptoms vary by vaginal lengthening treatment.<br><br>STUDY DESIGN: We conducted a cross-sectional study in 2019 using an online survey distributed by the Beautiful You MRKH Foundation via social media to individuals with Mayer-Rokitansky-K&#xfc;ster-Hauser syndrome. Demographics, age at and timing of diagnosis, information about vaginal lengthening treatment, urinary symptoms (Michigan Incontinence Symptom Index), prolapse symptoms (Pelvic Organ Prolapse Distress Inventory short-form version), and bowel symptoms (Bristol Stool Form Scale) were obtained. The inclusion criteria included self-reported diagnosis of m&#xfc;llerian agenesis and female sex. Respondents with a history of renal transplant or dialysis, completion of <85% of the survey, and non-English survey responses were excluded. Descriptive analyses were used to describe the sample population. Logistic regression, Kruskal-Wallis, and Fisher exact tests were used to compare the prevalence of pelvic floor symptoms and vaginal lengthening treatments. Associations between age and genitourinary symptoms were investigated with Spearman correlations.<br><br>RESULTS: Of 808 respondents, 615 met the inclusion criteria, representing 40 countries. 81% of respondents identified as white. The median age of the participants was 29 years (interquartile range, 24-36), with a median age at diagnosis of 16 years (interquartile range, 15-17). Among the 614 respondents, 331 (54%) had vaginal lengthening treatment, 130 of whom (39%) had undergone surgical vaginal lengthening. Of individuals with Mayer-Rokitansky-K&#xfc;ster-Hauser syndrome, 428 of 614 (70%) reported having had one or more urinary symptoms, and 339 of 428 (79%) reported being bothered by these symptoms. Urinary symptoms included urinary incontinence (210 of 614 [34%]), urinary frequency (245 of 614 [40%]), urinary urgency (248 of 614 [40%]), pain with urination (97 of 614 [16%]), and recurrent urinary tract infections (177 of 614 [29%]). Prolapse symptoms included lower abdominal pressure (248 of 612 [41%]), pelvic heaviness or dullness (177 of 610 [29%]), and vaginal bulge (68 of 609 [11%]). In addition, constipation was reported by 153 of 611 respondents (25%), and anal incontinence was reported by 153 of 608 (25%) respondents. Beside recent urinary incontinence (P=.003) and anal incontinence (P<.001), the prevalence of pelvic floor symptoms (P>.05) did not differ significantly between those with and without vaginal lengthening. Among those with surgical vaginal lengthening, symptomatic vaginal bulge was highest in individuals who underwent a bowel vaginoplasty procedure.<br><br>CONCLUSION: Urinary, prolapse, and bowel symptoms are common among individuals with Mayer-Rokitansky-K&#xfc;ster-Hauser syndrome and should be evaluated in this population. Overall, compared with no vaginal lengthening treatment, having vaginal lengthening treatment is not associated with substantial differences in the prevalence of pelvic floor symptoms, with the exception of recent urinary incontinence and anal incontinence. Our data suggested that bowel vaginoplasty may be associated with greater symptoms of vaginal bulge. More robust studies are needed to determine the impact of various vaginal lengthening treatments on pelvic floor symptoms.}, }
@article {pmid33620078, year = {2020}, author = {Sheh, A}, title = {The Gastrointestinal Microbiota of the Common Marmoset (Callithrix jacchus).}, journal = {ILAR journal}, volume = {61}, number = {2-3}, pages = {188-198}, pmid = {33620078}, issn = {1930-6180}, support = {P30 ES002109/ES/NIEHS NIH HHS/United States ; T32 OD010978/OD/NIH HHS/United States ; }, mesh = {Animals ; Bacteria ; Callithrix/microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Prospective Studies ; }, abstract = {The microbiota is heavily involved in both health and disease pathogenesis, but defining a normal, healthy microbiota in the common marmoset has been challenging. The aim of this review was to systematically review recent literature involving the gastrointestinal microbiome of common marmosets in health and disease. Twelve sources were included in this review. The gut microbiome composition was reviewed across institutions worldwide, and taxonomic shifts between healthy individuals were described. Unlike the human gut microbiome, which is dominated by Firmicutes and Bacteroidetes, the marmoset gut microbiome shows great plasticity across institutions, with 5 different phyla described as dominant in different healthy cohorts. Genera shared across institutions include Anaerobiospirillum, Bacteroides, Bifidobacterium, Collinsella, Fusobacterium, Megamonas, Megasphaera, Phascolarctobacterium, and Prevotella. Shifts in the abundance of Prevotella or Bifidobacterium or invasion by pathogens like Clostridium perfringens may be associated with disease. Changes in microbial composition have been described in healthy and diseased marmosets, but factors influencing the severe changes in microbial composition have not been established. Multi-institutional, prospective, and longitudinal studies that utilize multiple testing methodologies are required to determine sources of variability in the reporting of marmoset microbiomes. Furthermore, methods of microbial manipulation, whether by diet, enrichment, fecal microbiome transplantation, etc, need to be established to modulate and maintain robust and resilient microbiome communities in marmoset colonies and reduce the incidence of idiopathic gastrointestinal disease.}, }
@article {pmid33617596, year = {2021}, author = {Rungue, M and Melo, V and Martins, D and Campos, PC and Leles, G and Galvão, I and Mendes, V and Aganetti, M and Pedersen, &#xc1; and Assis, NRG and Santos, R and Cassali, GD and Godard, ALB and Martins, FS and Oliveira, SC and Vieira, AT}, title = {NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of Brucella abortus.}, journal = {PLoS neglected tropical diseases}, volume = {15}, number = {2}, pages = {e0009171}, pmid = {33617596}, issn = {1935-2735}, support = {R01 AI116453/AI/NIAID NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Brucella abortus ; Brucellosis/microbiology/*physiopathology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Host-Pathogen Interactions ; Intestines/*microbiology/*physiopathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Permeability ; Receptors, Cell Surface/genetics ; Specific Pathogen-Free Organisms ; }, abstract = {Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infection-Brucellosis, which has been associated with high morbidity rate in humans and severe economic losses in infected livestock. The natural route of infection is through oral and nasal mucosa but the invasion process through host gut mucosa is yet to be understood. Studies have examined the role of NLRP6 (NOD-like receptor family pyrin domain-containing-6 protein) in gut homeostasis and defense against pathogens. Here, we investigated the impact of gut microbiota and NLRP6 in a murine model of Ba oral infection. Nlrp6-/- and wild-type (WT) mice were infected by oral gavage with Ba and tissues samples were collected at different time points. Our results suggest that Ba oral infection leads to significant alterations in gut microbiota. Moreover, Nlrp6-/- mice were more resistant to infection, with decreased CFU in the liver and reduction in gut permeability when compared to the control group. Fecal microbiota transplantation from WT and Nlrp6-/- into germ-free mice reflected the gut permeability phenotype from the donors. Additionally, depletion of gut microbiota by broad-spectrum-antibiotic treatment prevented Ba replication in WT while favoring bacterial growth in Nlrp6-/-. Finally, we observed higher eosinophils in the gut and leukocytes in the blood of infected Nlrp6-/- compared to WT-infected mice, which might be associated to the Nlrp6-/- resistance phenotype. Altogether, these results indicated that gut microbiota composition is the major factor involved in the initial stages of pathogen host replication and partially also by the resistance phenotype observed in Nlrp6 -/- mice regulating host inflammation against Ba infection.}, }
@article {pmid33617526, year = {2021}, author = {Henson, MA}, title = {Computational modeling of the gut microbiota reveals putative metabolic mechanisms of recurrent Clostridioides difficile infection.}, journal = {PLoS computational biology}, volume = {17}, number = {2}, pages = {e1008782}, pmid = {33617526}, issn = {1553-7358}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria/genetics ; Bile Acids and Salts/metabolism ; *Clostridioides difficile ; Clostridium Infections/metabolism/*physiopathology ; Cluster Analysis ; Computer Simulation ; Enterobacteriaceae ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Middle Aged ; Principal Component Analysis ; RNA, Ribosomal, 16S/*metabolism ; Reinfection ; Reproducibility of Results ; Young Adult ; }, abstract = {Approximately 30% of patients who have Clostridioides difficile infection (CDI) will suffer at least one incident of reinfection. While the underlying causes of CDI recurrence are poorly understood, interactions between C. difficile and commensal gut bacteria are thought to play an important role. In this study, an in silico pipeline was used to process 16S rRNA gene amplicon sequence data of 225 stool samples from 93 CDI patients into sample-specific models of bacterial community metabolism. Clustered metabolite production rates generated from post-diagnosis samples generated a high Enterobacteriaceae abundance cluster containing disproportionately large numbers of recurrent samples and patients. This cluster was predicted to have significantly reduced capabilities for secondary bile acid synthesis but elevated capabilities for aromatic amino acid catabolism. When applied to 16S sequence data of 40 samples from fecal microbiota transplantation (FMT) patients suffering from recurrent CDI and their stool donors, the community modeling method generated a high Enterobacteriaceae abundance cluster with a disproportionate large number of pre-FMT samples. This cluster also was predicted to exhibit reduced secondary bile acid synthesis and elevated aromatic amino acid catabolism. Collectively, these in silico predictions suggest that Enterobacteriaceae may create a gut environment favorable for C. difficile spore germination and/or toxin synthesis.}, }
@article {pmid33615992, year = {2021}, author = {Pham, VT and Fehlbaum, S and Seifert, N and Richard, N and Bruins, MJ and Sybesma, W and Rehman, A and Steinert, RE}, title = {Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome- a pilot study.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-20}, pmid = {33615992}, issn = {1949-0984}, mesh = {Ascorbic Acid/administration &amp; dosage/pharmacokinetics ; Bacteria/classification/*growth &amp; development/metabolism ; Caco-2 Cells ; Colon/*metabolism/microbiology ; Cytokines/metabolism ; *Dietary Supplements ; Double-Blind Method ; Drug Delivery Systems ; Fatty Acids, Volatile/metabolism ; Feces/microbiology ; Fermentation ; Gastrointestinal Microbiome/*physiology ; HT29 Cells ; Humans ; Pilot Projects ; Riboflavin/administration &amp; dosage/pharmacokinetics ; Vitamin A/administration &amp; dosage/pharmacokinetics ; Vitamin D/administration &amp; dosage/pharmacokinetics ; Vitamin E/administration &amp; dosage/pharmacokinetics ; Vitamins/*administration &amp; dosage/pharmacokinetics ; }, abstract = {An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.}, }
@article {pmid33614028, year = {2021}, author = {D Goldenberg, S and Merrick, B}, title = {The role of faecal microbiota transplantation: looking beyond Clostridioides difficile infection.}, journal = {Therapeutic advances in infectious disease}, volume = {8}, number = {}, pages = {2049936120981526}, pmid = {33614028}, issn = {2049-9361}, support = {PB-PG-0418-20007/DH_/Department of Health/United Kingdom ; }, abstract = {Faecal microbiota transplantation (FMT) is the transfer of screened and minimally processed faecal material from a 'healthy' donor to 'diseased' recipient. It has an established role, and is recommended as a therapeutic strategy, in the management of recurrent Clostridioides difficile infection (CDI). Recognition that gut dysbiosis is associated with, and may contribute to, numerous disease states has led to interest in exploiting FMT to 'correct' this microbial imbalance. Conditions for which it is proposed to be beneficial include inflammatory bowel disease, irritable bowel syndrome, liver disease and hepatic encephalopathy, neuropsychiatric conditions such as depression and anxiety, systemic inflammatory states like sepsis, and even coronavirus disease 2019. To understand what role, if any, FMT may play in the management of these conditions, it is important to consider the potential risks and benefits of the therapy. Regardless, there are several barriers to its more widespread adoption, which include incompletely understood mechanism of action (especially outside of CDI), inability to standardise treatment, disagreement on its active ingredients and how it should be regulated, and lack of long-term outcome and safety data. Whilst the transfer of faecal material from one individual to another to treat ailments or improve health has a history dating back thousands of years, there are fewer than 10 randomised controlled trials supporting its use. Moving forward, it will be imperative to gather as much data from FMT donors and recipients over as long a timeframe as possible, and for trials to be conducted with rigorous methodology, including appropriate control groups, in order to best understand the utility of FMT for indications beyond CDI. This review discusses the history of FMT, its appreciable mechanisms of action with reference to CDI, indications for FMT with an emerging evidence base above and beyond CDI, and future perspectives on the field.}, }
@article {pmid33613943, year = {2021}, author = {Mullish, BH and Quraishi, MN and Segal, JP and Ianiro, G and Iqbal, TH}, title = {The gut microbiome: what every gastroenterologist needs to know.}, journal = {Frontline gastroenterology}, volume = {12}, number = {2}, pages = {118-127}, pmid = {33613943}, issn = {2041-4137}, support = {13/179/01/DH_/Department of Health/United Kingdom ; }, abstract = {The mucosal surfaces of the body are characterised by complex, specialised microbial communities, often referred to as the microbiome. However, only much more recently-with the development of technologies allowing exploration of the composition and functionality of these communities-has meaningful research in this area become feasible. Over the past few years, there has been rapid growth in interest in the gut microbiome in particular, and its potential contribution to gastrointestinal and liver disease. This interest has already extended beyond clinicians to pharmaceutical companies, medical regulators and other stakeholders, and is high profile among patients and the lay public in general. Such expansion of knowledge holds the intriguing potential for translation into novel diagnostics and therapeutics; however, being such a nascent field, there remain many uncertainties, unanswered questions and areas of debate.}, }
@article {pmid33613491, year = {2021}, author = {Qi, R and Zhang, Z and Wang, J and Qiu, X and Wang, Q and Yang, F and Huang, J and Liu, Z}, title = {Introduction of Colonic and Fecal Microbiota From an Adult Pig Differently Affects the Growth, Gut Health, Intestinal Microbiota and Blood Metabolome of Newborn Piglets.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {623673}, pmid = {33613491}, issn = {1664-302X}, abstract = {Microbiota transplantation is a rapid and effective method for changing and reshaping the intestinal microbiota and metabolic profile in humans and animals. This study compared the different influences of the introduction of fecal microbes and colonic microbes from a fat, adult pig in newborn pigs. Both colonic microbiota transplantation (CMT) and fecal microbiota transplantation (FMT) promoted growth and improved gut functions in suckling pigs up to weaning. FMT was more beneficial for body weight gain and body fat deposition in piglets, while CMT was more beneficial for intestinal health and mucosal immunity. 16S rDNA sequence analysis indicated that both CMT and FMT significantly increased the abundances of beneficial or functional bacteria, such as Lactobacillus and Prevotella_2 genera, in the piglets, and reduced the abundances of harmful bacteria, such as Escherichia-Shigella. Blood metabolome analysis showed that transplantation, especially FMT, enhanced lipid metabolism in piglets. In addition, while CMT also changed amino acid metabolism and increased anti-inflammatory metabolites such as 3-indoleacetic acid and 3-indolepropionic acid in piglets, FMT did not. Of note, FMT damaged the intestinal barrier of piglets to a certain extent and increased the levels of inflammatory factors in the blood that are potentially harmful to the health of pigs. Taken together, these results suggested that intestinal and fecal microbiota transplantations elicited similar but different physiological effects on young animals, so the application of microbiota transplantation in animal production requires the careful selection and evaluation of source bacteria.}, }
@article {pmid33609303, year = {2021}, author = {Barrow, F and Khan, S and Fredrickson, G and Wang, H and Dietsche, K and Parthiban, P and Robert, S and Kaiser, T and Winer, S and Herman, A and Adeyi, O and Mouzaki, M and Khoruts, A and Hogquist, KA and Staley, C and Winer, DA and Revelo, XS}, title = {Microbiota-Driven Activation of Intrahepatic B Cells Aggravates NASH Through Innate and Adaptive Signaling.}, journal = {Hepatology (Baltimore, Md.)}, volume = {74}, number = {2}, pages = {704-722}, pmid = {33609303}, issn = {1527-3350}, support = {R01 DK122056/DK/NIDDK NIH HHS/United States ; FDN-148385//CIHR/Canada ; }, mesh = {Adaptive Immunity ; Animals ; B-Lymphocytes/*immunology/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunity, Innate ; Liver/cytology/immunology/*pathology ; Lymphocyte Activation ; Male ; Mice ; Mice, Transgenic ; Myeloid Differentiation Factor 88/genetics/metabolism ; Non-alcoholic Fatty Liver Disease/*immunology/pathology ; RNA-Seq ; Signal Transduction/immunology ; Single-Cell Analysis ; }, abstract = {BACKGROUND AND AIMS: Nonalcoholic steatohepatitis is rapidly becoming the leading cause of liver failure and indication for liver transplantation. Hepatic inflammation is a key feature of NASH but the immune pathways involved in this process are poorly understood. B lymphocytes are cells of the adaptive immune system that are critical regulators of immune responses. However, the role of B cells in the pathogenesis of NASH and the potential mechanisms leading to their activation in the liver are unclear.<br><br>APPROACH AND RESULTS: In this study, we report that NASH livers accumulate B cells with elevated pro-inflammatory cytokine secretion and antigen-presentation ability. Single-cell and bulk RNA sequencing of intrahepatic B cells from mice with NASH unveiled a transcriptional landscape that reflects their pro-inflammatory function. Accordingly, B-cell deficiency ameliorated NASH progression, and adoptively transferring B cells from NASH livers recapitulates the disease. Mechanistically, B-cell activation during NASH involves signaling through the innate adaptor myeloid differentiation primary response protein 88 (MyD88) as B cell-specific deletion of MyD88 reduced hepatic T cell-mediated inflammation and fibrosis, but not steatosis. In addition, activation of intrahepatic B cells implicates B cell-receptor signaling, delineating a synergy between innate and adaptive mechanisms of antigen recognition. Furthermore, fecal microbiota transplantation of human NAFLD gut microbiotas into recipient mice promoted the progression of NASH by increasing the accumulation and activation of intrahepatic B cells, suggesting that gut microbial factors drive the pathogenic function of B cells during NASH.<br><br>CONCLUSION: Our findings reveal that a gut microbiota-driven activation of intrahepatic B cells leads to hepatic inflammation and fibrosis during the progression of NASH through innate and adaptive immune mechanisms.}, }
@article {pmid33608575, year = {2021}, author = {Kazemian, N and Ramezankhani, M and Sehgal, A and Khalid, FM and Kalkhoran, AHZ and Narayan, A and Wong, GK and Kao, D and Pakpour, S}, title = {Author Correction: The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4546}, doi = {10.1038/s41598-021-82644-z}, pmid = {33608575}, issn = {2045-2322}, }
@article {pmid33607299, year = {2020}, author = {Wang, B and Zhu, S and Liu, Z and Wei, H and Zhang, L and He, M and Pei, F and Zhang, J and Sun, Q and Duan, L}, title = {Increased Expression of Colonic Mucosal Melatonin in Patients with Irritable Bowel Syndrome Correlated with Gut Dysbiosis.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {18}, number = {6}, pages = {708-720}, pmid = {33607299}, issn = {2210-3244}, mesh = {Animals ; Diarrhea ; Dysbiosis ; Humans ; *Irritable Bowel Syndrome ; *Melatonin ; Rats ; }, abstract = {Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome (IBS). Melatonin plays a beneficial role in gut motility and immunity. However, altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear. Therefore, we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and explore their relationship in germ-free (GF) rats and BON-1 cells. Thirty-two IBS-D patients and twenty-eight healthy controls (HCs) were recruited. Fecal specimens from IBS-D patients and HCs were separately transplanted into GF rats by gavage. The levels of colon mucosal melatonin were assessed by immunohistochemical methods, and fecal microbiota communities were analyzed using 16S rDNA sequencing. The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA. Melatonin levels were significantly increased and negatively correlated with visceral hypersensitivity in IBS-D patients. GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels. Butyrate-producing Clostridium cluster XIVa species, such as Roseburia species and Lachnospira species, were positively related to colonic mucosal melatonin expression. Butyrate significantly increased melatonin secretion in BON-1 cells. Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D. Moreover, some Clostridium cluster XIVa species could increase melatonin expression via butyrate production. Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.}, }
@article {pmid33605497, year = {2021}, author = {Zhang, LT and Westblade, LF and Iqbal, F and Taylor, MR and Chung, A and Satlin, MJ and Magruder, M and Edusei, E and Albakry, S and Botticelli, B and Robertson, A and Alston, T and Dadhania, DM and Lubetzky, M and Hirota, SA and Greenway, SC and Lee, JR}, title = {Gut microbiota profiles and fecal beta-glucuronidase activity in kidney transplant recipients with and without post-transplant diarrhea.}, journal = {Clinical transplantation}, volume = {35}, number = {5}, pages = {e14260}, doi = {10.1111/ctr.14260}, pmid = {33605497}, issn = {1399-0012}, support = {K23 AI124464/AI/NIAID NIH HHS/United States ; }, mesh = {Diarrhea ; *Gastrointestinal Microbiome ; Glucuronidase ; Humans ; *Kidney Transplantation ; RNA, Ribosomal, 16S ; }, abstract = {Post-transplant diarrhea is a common complication after solid organ transplantation and is frequently attributed to the widely prescribed immunosuppressant mycophenolate mofetil (MMF). Given recent work identifying the relationship between MMF toxicity and gut bacterial β-glucuronidase activity, we evaluated the relationship between gut microbiota composition, fecal β-glucuronidase activity, and post-transplant diarrhea. We recruited 97 kidney transplant recipients and profiled the gut microbiota in 273 fecal specimens using 16S rRNA gene sequencing. We further characterized fecal β-glucuronidase activity in a subset of this cohort. Kidney transplant recipients with post-transplant diarrhea had decreased gut microbial diversity and decreased relative gut abundances of 12 genera when compared to those without post-transplant diarrhea (adjusted p value < .15, Wilcoxon rank sum test). Among the kidney transplant recipients with post-transplant diarrhea, those with higher fecal β-glucuronidase activity had a more prolonged course of diarrhea (≥7 days) compared to patients with lower fecal β-glucuronidase activity (91% vs 40%, p = .02, Fisher's exact test). Our data reveal post-transplant diarrhea as a complex phenomenon with decreased gut microbial diversity and commensal gut organisms. This study further links commensal bacterial metabolism with an important clinical outcome measure, suggesting fecal β-glucuronidase activity could be a novel biomarker for gastrointestinal-related MMF toxicity.}, }
@article {pmid33605457, year = {2021}, author = {Bueno, F and Albert, E and Giménez, E and Piñana, JL and Pérez, A and Dolores Gómez, M and Hernández-Boluda, JC and Gonzalez-Barberá, EM and Montoro, J and Buesa, J and Guerreiro, M and Balaguer-Roselló, A and Hernani, R and Sanz, J and Solano, C and Navarro, D}, title = {An investigation of the potential association between gastrointestinal viral and bacterial infection and development of intestinal acute graft versus host disease following allogeneic hematopoietic stem cell transplantation.}, journal = {Journal of medical virology}, volume = {93}, number = {8}, pages = {4773-4779}, doi = {10.1002/jmv.26892}, pmid = {33605457}, issn = {1096-9071}, mesh = {Acute Disease ; Adolescent ; Adult ; Aged ; Bacteria/classification/isolation &amp; purification/pathogenicity ; Bacterial Infections/*complications ; Disease Susceptibility ; Feces ; Female ; Gastrointestinal Diseases/complications/*microbiology/*virology ; Graft vs Host Disease/*etiology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Proportional Hazards Models ; Prospective Studies ; Virus Diseases/*complications ; Viruses/classification/genetics/isolation &amp; purification ; Young Adult ; }, abstract = {It is uncertain whether gastrointestinal (GI) infection caused by viral and bacterial pathogens may predispose to gastrointestinal acute Graft-versus-host disease (aGvHD-GI) in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). We investigated the potential association between detection of enteropathogenic viruses or bacteria in stools and subsequent occurrence of aGvHD-GI in a cohort of 121 allo-HSCT patients. Eighty-six out of 121 patients (71%) had acute diarrhea and underwent screening for primary GI pathogens by molecular diagnostic methods. One or more GI pathogens were detected in 27 out of the 86 patients with diarrhea (31.3%). Specifically, Clostridioides difficile was found in 16 patients (18.6%), enteropathogenic viruses in 11 patients (12.7%) (Astrovirus, n = 4; Norovirus, n = 2; Sapovirus, n = 2; Adenovirus, n = 2; and Rotavirus, n = 1), and Campylobacter spp. in two patients (2.3%). Thirty patients were diagnosed with all grade aGvHD-GI by histopathology. Detection of primary GI pathogens was achieved in 12 out of 30 patients (Clostridium difficile, n = 5; enteric viruses, n = 8; Campylobacter spp., n = 1) who either subsequently developed (n = 9) or previously had (n = 3) grade I-IV IaGvHD (n = 9). Neither the detection of these microorganisms (all combined), enteric viruses, nor C. difficile was significantly associated with subsequent aGvHD-GI development in Cox models (hazard ratio [HR] = 1.11, p = .80; HR = 1.64, p = .62; HR = 0.75, p = .64, respectively). Analogous results were obtained when grade II-IV aGvHD-GI was selected as the clinical outcome. In summary, data in the current study did not support an association between GI infection and subsequent occurrence of aGvHD-GI in an unselected cohort of allo-HSCT recipients.}, }
@article {pmid33602945, year = {2021}, author = {Serrano-Villar, S and Talavera-Rodríguez, A and Gosalbes, MJ and Madrid, N and Pérez-Molina, JA and Elliott, RJ and Navia, B and Lanza, VF and Vallejo, A and Osman, M and Dronda, F and Budree, S and Zamora, J and Gutiérrez, C and Manzano, M and Vivancos, MJ and Ron, R and Martínez-Sanz, J and Herrera, S and Ansa, U and Moya, A and Moreno, S}, title = {Fecal microbiota transplantation in HIV: A pilot placebo-controlled study.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {1139}, pmid = {33602945}, issn = {2041-1723}, mesh = {Biodiversity ; Biomarkers/blood ; Discriminant Analysis ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; HIV Infections/blood/*microbiology/*therapy ; Humans ; Male ; Middle Aged ; Phylogeny ; Pilot Projects ; Placebos ; Tissue Donors ; }, abstract = {Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor's microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.}, }
@article {pmid33598642, year = {2021}, author = {Hua, H and Zhang, Y and Zhao, F and Chen, K and Wu, T and Liu, Q and Huang, S and Zhang, A and Jia, Z}, title = {Celastrol inhibits intestinal lipid absorption by reprofiling the gut microbiota to attenuate high-fat diet-induced obesity.}, journal = {iScience}, volume = {24}, number = {2}, pages = {102077}, pmid = {33598642}, issn = {2589-0042}, abstract = {Celastrol, a compound extracted from traditional Chinese medicine, has been reported as a potent anti-obesity agent with controversial mechanisms. Here both C57BL/6J and leptin-deficient (ob/ob) mice fed a high-fat diet (HFD) displayed body weight loss after celastrol therapy, opposing the previous viewpoint that celastrol improves obesity by sensitizing leptin signaling. More importantly, celastrol downregulated lipid transporters in the intestine, increased lipid excretion in feces, and reduced body weight gain in HFD mice. Meanwhile, analysis of gut microbiota revealed that celastrol altered the gut microbiota composition in HFD-fed mice, and modulating gut microbiota by antibiotics or fecal microbiota transplantation blocked the celastrol effect on intestinal lipid transport and body weight gain, suggesting a critical role of the gut microbiota composition in mediating the anti-obesity role of celastrol under HFD. Together, the findings revealed that celastrol reduces intestinal lipid absorption to antagonize obesity by resetting the gut microbiota profile under HFD feeding.}, }
@article {pmid33598417, year = {2020}, author = {Bendriss, G and Al-Ali, D and Shafiq, A and Laswi, I and Mhaimeed, N and Salameh, M and Burney, Z and Pillai, K and Chaari, A and Zakaria, D and Yousri, NA}, title = {Targeting the gut microbiome: A brief report on the awareness, practice, and readiness to engage in clinical interventions in Qatar.}, journal = {Qatar medical journal}, volume = {2020}, number = {3}, pages = {47}, pmid = {33598417}, issn = {0253-8253}, abstract = {BACKGROUND: There has been a growing global interest in the role of gut microbiota in the pathogenesis of diseases and the potentials of targeting the microbiome in clinical interventions. Very few clinical studies in Qatar focused on gut microbiome. This study aimed to assess the awareness of healthcare professionals, scientists, and the general public on the role of gut microbiota in health and diseases and, more specifically, in disorders of the gut-brain axis such as neurodevelopmental disorders (NDDs) or gastrointestinal (GI) disorders. It also aimed to evaluate the readiness of the population to engage in clinical trials involving dietary interventions or fecal transplants.<br><br>METHODS: A total of 156 participants were recruited to answer questionnaires-from healthcare professionals and scientists (HSs; n&#xa0;=&#xa0;44) and the general public (n&#xa0;=&#xa0;112). Participants from the general public self-reported their diagnosis of NDDs-autism or attention deficit hyperactivity disorder (n&#xa0;=&#xa0;36)-or GI diseases or disorders (n&#xa0;=&#xa0;18) or as having none of them (n&#xa0;=&#xa0;58). Two questionnaires for HSs and for the general public were distributed, and basic descriptive and statistical analyses were conducted using the Fisher's exact test.<br><br>RESULTS: Among the participating HSs, 95% admitted that they had minimum to no knowledge on the role of gut microbes in health and diseases, and only 15.9% felt that their peers were knowledgeable about it. Nevertheless, 97.7% of HSs thought that gut microbiota should be considered when devising treatment plans as 79.1% believed that gut dysbiosis is involved in the pathogenesis of diseases. For the general public, 54% stated that they have read about studies on the potential benefits of microbes in the prevention, treatment, and management of diseases, with a higher proportion of them belonging to the GI group (p&#xa0;=&#xa0;0.0523). The GI group was also more aware of the existence of the use of fecal transplants for treating their condition (p&#xa0;=&#xa0;0.01935). Awareness was also reflected in participants' attempts to engage in dietary changes, as 40% tried a dietary intervention, which has noticeably changed their or their child's symptoms. This study reported a highly significant association between being exposed to multiple antibiotic courses before three years of age and being part of the NDD group (p&#xa0;=&#xa0;0.0003). Public readiness to engage in interventions that target the gut microbiome, such as intensive dietary interventions or even fecal transplants, was perceived by HSs to be lower than what was stated by the public, with 87.96% of public being ready to engage in intensive dietary interventions and 66.98% in fecal transplants.<br><br>CONCLUSION: The study revealed that the role of gut microbes in health and diseases, and especially through the gut-brain axis, is still unclear in both the scientific community and general public. While acknowledging the importance of gut microbes, the lack of information regarding the link between lifestyle and gut microbes is considered to hold the public in the precontemplation/contemplation stages of the transtheoretical model of behavioral change. An interdisciplinary approach to new knowledge produced by microbiome studies is needed to run awareness campaigns and continue professional development activities on the benefits of lifestyle-based modulation of gut microbiome, thus engaging the general public in lifestyle changes and facilitating clinical research in human microbiome investigations in Qatar.}, }
@article {pmid33598269, year = {2021}, author = {Zeng, J and Peng, L and Zheng, W and Huang, F and Zhang, N and Wu, D and Yang, Y}, title = {Fecal microbiota transplantation for rheumatoid arthritis: A case report.}, journal = {Clinical case reports}, volume = {9}, number = {2}, pages = {906-909}, pmid = {33598269}, issn = {2050-0904}, abstract = {No previous case of using fecal microbiota transplantation (FMT) to treat rheumatoid arthritis (RA) has been reported. We report a case of a patient with refractory RA successfully treated with FMT indicating that FMT may have a good therapeutic effect on RA.}, }
@article {pmid33595467, year = {2021}, author = {Shivaji, S}, title = {A systematic review of gut microbiome and ocular inflammatory diseases: Are they associated?.}, journal = {Indian journal of ophthalmology}, volume = {69}, number = {3}, pages = {535-542}, pmid = {33595467}, issn = {1998-3689}, mesh = {Bacteria ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Keratitis ; *Microbiota ; }, abstract = {The primary focus of this review was to establish the possible association of dysbiotic changes in the gut bacterial microbiomes with both intestinal and extra-intestinal diseases with emphasis on ocular diseases such as bacterial keratitis, fungal keratitis, uveitis, age-related macular degeneration, and ocular mucosal diseases. For this particular purpose, a systematic search was conducted using PubMed and Google Scholar for publications related to gut microbiome and human health (using the keywords: gut microbiome, ocular disease, dysbiosis, keratitis, uveitis, and AMD). The predictions are that microbiome studies would help to unravel dysbiotic changes in the gut bacterial microbiome at the taxonomic and functional level and thus form the basis to mitigate inflammatory diseases of the eye by using nutritional supplements or fecal microbiota transplantation.}, }
@article {pmid33595259, year = {2021}, author = {Li, S and Guo, H and Xu, X and Hua, R and Zhao, Q and Li, J and Lv, J and Li, J}, title = {Therapeutic Methods for Gut Microbiota Modification in Lipopolysaccharide-Associated Encephalopathy.}, journal = {Shock (Augusta, Ga.)}, volume = {56}, number = {5}, pages = {824-831}, doi = {10.1097/SHK.0000000000001758}, pmid = {33595259}, issn = {1540-0514}, mesh = {Animals ; Brain Diseases/chemically induced/*microbiology/*therapy ; Dysbiosis/*therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Lipopolysaccharides ; Male ; *Prebiotics ; Probiotics/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; *Synbiotics ; Treatment Outcome ; }, abstract = {OBJECTIVE: To compare the efficacy of four therapeutic methods to modify gut microbiota dysbiosis and brain dysfunction in septic rats.<br><br>METHODS: Rats were treated with fecal microbiota transplantation, prebiotics, probiotics, and synbiotics after exposure to lipopolysaccharide. The diversity and composition of gut microbiota, electroencephalogram values, and the concentrations of TNF-&#x3b1;, IL-1&#x3b2;, and IL-6 in the cortex were analyzed.<br><br>RESULTS: Fecal microbiota transplantation was the most efficacious method to restore intestinal microbial diversity and exert the best corrective effects in modulating microbial composition in septic rats. More interestingly, fecal microbiota transplantation exerted the best protective effects in brain dysfunction in septic rats.<br><br>CONCLUSION: Among the four methods, fecal microbiota transplantation was the most useful method to modify the dysbiosis of intestinal microbiota and improve brain function in septic rats. These findings reveal the protective consequence of microbiota modification, and the findings suggest opportunities to improve brain function in sepsis.}, }
@article {pmid33593727, year = {2021}, author = {Brooks, EF and Bhatt, AS}, title = {The gut microbiome: a missing link in understanding the gastrointestinal manifestations of COVID-19?.}, journal = {Cold Spring Harbor molecular case studies}, volume = {7}, number = {2}, pages = {}, pmid = {33593727}, issn = {2373-2873}, mesh = {Abdominal Pain/diagnosis/*etiology/microbiology/pathology ; Animals ; COVID-19/*complications/diagnosis/microbiology/pathology ; Diarrhea/diagnosis/*etiology/microbiology/pathology ; Feces/microbiology/virology ; *Gastrointestinal Microbiome ; Humans ; Nausea/diagnosis/*etiology/microbiology/pathology ; SARS-CoV-2/isolation &amp; purification ; Vomiting/diagnosis/*etiology/microbiology/pathology ; }, abstract = {Coronavirus disease 2019 (COVID-19), which is caused by infection with SARS-CoV-2, presents with a broad constellation of both respiratory and nonrespiratory symptoms, although it is primarily considered a respiratory disease. Gastrointestinal symptoms-including nausea, abdominal pain, vomiting, and diarrhea-rank chief among these. When coupled with the presence of viral RNA in fecal samples, the presence of gastrointestinal symptoms raises relevant questions regarding whether SARS-CoV-2 can productively infect the upper or lower gastrointestinal tract. Despite the well-documented prevalence of gastrointestinal symptoms and the high rate of SARS-CoV-2 fecal RNA shedding, the biological, clinical, and epidemiological relevance of these findings is unclear. Furthermore, the isolation of replication-competent virus from fecal samples has not been reproducibly and rigorously demonstrated. Although SARS-CoV-2 shedding likely occurs in a high proportion of patients, gastrointestinal symptoms affect only a subset of individuals. Herein, we summarize what is known about gastrointestinal symptoms and fecal viral shedding in COVID-19, explore the role of the gut microbiome in other respiratory diseases, speculate on the role of the gut microbiota in COVID-19, and discuss potential future directions. Taking these concepts together, we propose that studying gut microbiota perturbations in COVID-19 will enhance our understanding of the symptomology and pathophysiology of this novel devastating disease.}, }
@article {pmid33593430, year = {2021}, author = {Langdon, A and Schwartz, DJ and Bulow, C and Sun, X and Hink, T and Reske, KA and Jones, C and Burnham, CD and Dubberke, ER and Dantas, G and , }, title = {Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study.}, journal = {Genome medicine}, volume = {13}, number = {1}, pages = {28}, pmid = {33593430}, issn = {1756-994X}, support = {T32 HG000045/HG/NHGRI NIH HHS/United States ; R01 AI123394/AI/NIAID NIH HHS/United States ; TL1 TR000449/TR/NCATS NIH HHS/United States ; R01 HD092414/HD/NICHD NIH HHS/United States ; TL1 TR000449/NH/NIH HHS/United States ; }, mesh = {Bacteria/genetics/*growth &amp; development ; Clostridium Infections/*microbiology/*therapy ; *Drug Resistance, Microbial/genetics ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Humans ; Intestines/*microbiology ; Phylogeny ; Principal Component Analysis ; Recurrence ; Time Factors ; Tissue Donors ; }, abstract = {BACKGROUND: Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI.<br><br>METHODS: An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N&#x2009;=&#x2009;16) or two doses of RBX2660 (N&#x2009;=&#x2009;13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6&#x2009;months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms.<br><br>RESULTS: Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted.<br><br>CONCLUSIONS: Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT01925417 ; registered on August 19, 2013.}, }
@article {pmid33593429, year = {2021}, author = {Moshkelgosha, S and Verhasselt, HL and Masetti, G and Covelli, D and Biscarini, F and Horstmann, M and Daser, A and Westendorf, AM and Jesenek, C and Philipp, S and Diaz-Cano, S and Banga, JP and Michael, D and Plummer, S and Marchesi, JR and Eckstein, A and Ludgate, M and Berchner-Pfannschmidt, U and , }, title = {Modulating gut microbiota in a mouse model of Graves' orbitopathy and its impact on induced disease.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {45}, pmid = {33593429}, issn = {2049-2618}, mesh = {Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Graves Ophthalmopathy/immunology/metabolism/*microbiology/pathology ; Humans ; Mice ; Mice, Inbred BALB C ; }, abstract = {BACKGROUND: Graves' disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves' orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks).<br><br>RESULTS: In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. Firmicutes were increased, and Bacteroidetes reduced relative to ddH2O-&#x3b2;gal; CCL5&#xa0;was&#xa0;increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with Akkermansia spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors' microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genus Bacteroides, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25[+] Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO.<br><br>CONCLUSIONS: These results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments. Video abstract.}, }
@article {pmid33592037, year = {2021}, author = {Usher-Smith, JA and Mills, KM and Riedinger, C and Saunders, CL and Helsingen, LM and Lytvyn, L and Buskermolen, M and Lansdorp-Vogelaar, I and Bretthauer, M and Guyatt, G and Griffin, SJ}, title = {The impact of information about different absolute benefits and harms on intention to participate in colorectal cancer screening: A think-aloud study and online randomised experiment.}, journal = {PloS one}, volume = {16}, number = {2}, pages = {e0246991}, pmid = {33592037}, issn = {1932-6203}, support = {21464/CRUK_/Cancer Research UK/United Kingdom ; MC_UU_00006/6/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; C55650/A21464/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Colorectal Neoplasms/*diagnosis ; *Cost-Benefit Analysis ; *Decision Making ; Female ; Humans ; *Intention ; *Internet ; Male ; Mass Screening/*psychology/statistics &amp; numerical data ; Middle Aged ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: There is considerable heterogeneity in individuals' risk of disease and thus the absolute benefits and harms of population-wide screening programmes. Using colorectal cancer (CRC) screening as an exemplar, we explored how people make decisions about screening when presented with information about absolute benefits and harms, and how those preferences vary with baseline risk, between screening tests and between individuals.<br><br>METHOD: We conducted two linked studies with members of the public: a think-aloud study exploring decision making in-depth and an online randomised experiment quantifying preferences. In both, participants completed a web-based survey including information about three screening tests (colonoscopy, sigmoidoscopy, and faecal immunochemical testing) and then up to nine scenarios comparing screening to no screening for three levels of baseline risk (1%, 3% and 5% over 15 years) and the three screening tests. Participants reported, after each scenario, whether they would opt for screening (yes/no).<br><br>RESULTS: Of the 20 participants in the think-aloud study 13 did not consider absolute benefits or harms when making decisions concerning CRC screening. In the online experiment (n = 978), 60% expressed intention to attend at 1% risk of CRC, 70% at 3% and 77% at 5%, with no differences between screening tests. At an individual level, 535 (54.7%) would attend at all three risk levels and 178 (18.2%) at none. The 27% whose intention varied by baseline risk were more likely to be younger, without a family history of CRC, and without a prior history of screening.<br><br>CONCLUSIONS: Most people in our population were not influenced by the range of absolute benefits and harms associated with CRC screening presented. For an appreciable minority, however, magnitude of benefit was important.}, }
@article {pmid33592026, year = {2021}, author = {Michael, H and Paim, FC and Miyazaki, A and Langel, SN and Fischer, DD and Chepngeno, J and Goodman, SD and Rajashekara, G and Saif, LJ and Vlasova, AN}, title = {Escherichia coli Nissle 1917 administered as a dextranomar microsphere biofilm enhances immune responses against human rotavirus in a neonatal malnourished pig model colonized with human infant fecal microbiota.}, journal = {PloS one}, volume = {16}, number = {2}, pages = {e0246193}, pmid = {33592026}, issn = {1932-6203}, support = {T32 AI007392/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn ; Antibodies, Viral/immunology ; B-Lymphocytes/immunology ; *Biofilms ; Dextrans/*chemistry ; Disease Models, Animal ; Escherichia coli/*physiology ; Feces/*microbiology ; Malnutrition/microbiology/*virology ; *Microbiota ; Microspheres ; RNA, Messenger/genetics ; Rotavirus/*immunology/physiology ; SOX9 Transcription Factor/genetics ; Swine ; Up-Regulation ; }, abstract = {Human rotavirus (HRV) is a leading cause of diarrhea in children. It causes significant morbidity and mortality, especially in low- and middle-income countries (LMICs), where HRV vaccine efficacy is low. The probiotic Escherichia coli Nissle (EcN) 1917 has been widely used in the treatment of enteric diseases in humans. However, repeated doses of EcN are required to achieve maximum beneficial effects. Administration of EcN on a microsphere biofilm could increase probiotic stability and persistence, thus maximizing health benefits without repeated administrations. Our aim was to investigate immune enhancement by the probiotic EcN adhered to a dextranomar microsphere biofilm (EcN biofilm) in a neonatal, malnourished piglet model transplanted with human infant fecal microbiota (HIFM) and infected with rotavirus. To create malnourishment, pigs were fed a reduced amount of bovine milk. Decreased HRV fecal shedding and protection from diarrhea were evident in the EcN biofilm treated piglets compared with EcN suspension and control groups. Moreover, EcN biofilm treatment enhanced natural killer cell activity in blood mononuclear cells (MNCs). Increased frequencies of activated plasmacytoid dendritic cells (pDC) in systemic and intestinal tissues and activated conventional dendritic cells (cDC) in blood and duodenum were also observed in EcN biofilm as compared with EcN suspension treated pigs. Furthermore, EcN biofilm treated pigs had increased frequencies of systemic activated and resting/memory antibody forming B cells and IgA+ B cells in the systemic tissues. Similarly, the mean numbers of systemic and intestinal HRV-specific IgA antibody secreting cells (ASCs), as well as HRV-specific IgA antibody titers in serum and small intestinal contents, were increased in the EcN biofilm treated group. In summary EcN biofilm enhanced innate and B cell immune responses after HRV infection and ameliorated diarrhea following HRV challenge in a malnourished, HIFM pig model.}, }
@article {pmid33588762, year = {2021}, author = {Chen, Q and He, Z and Zhuo, Y and Li, S and Yang, W and Hu, L and Zhong, H}, title = {Rubidium chloride modulated the fecal microbiota community in mice.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {46}, pmid = {33588762}, issn = {1471-2180}, support = {51774339//National Natural Science Foundation of China/ ; 1053320184188//Fundamental Research Funds for Central Universities of the Central South University (CN)/ ; }, mesh = {Animals ; Antineoplastic Agents/administration &amp; dosage ; Bacteria/classification/*drug effects/*genetics ; Chlorides/*administration &amp; dosage ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome/*drug effects/genetics ; Male ; Mice ; Rubidium/*administration &amp; dosage ; Sequence Analysis, DNA ; Specific Pathogen-Free Organisms ; }, abstract = {BACKGROUND: The microbiota plays an important role in host health. Although rubidium (Rb) has been used to study its effects on depression and cancers, the interaction between microbial commensals and Rb is still unexplored. To gain the knowledge of the relationship between Rb and microbes, 51 mice receiving RbCl-based treatment and 13 untreated mice were evaluated for their characteristics and bacterial microbiome changes.<br><br>RESULTS: The 16S ribosomal RNA gene sequencing of fecal microbiota showed that RbCl generally maintained fecal microbial community diversity, while the shifts in fecal microbial composition were apparent after RbCl exposure. RbCl significantly enhanced the abundances of Rikenellaceae, Alistipes, Clostridium XlVa and sulfate-reducing bacteria including Deltaproteobacteria, Desulfovibrionales, Desulfovibrionaceae and Desulfovibrio, but significantly inhibited the abundances of Tenericutes, Mollicutes, Anaeroplasmatales, Anaeroplasmataceae and Anaeroplasma lineages. With regarding to the archaea, we only observed two less richness archaea Sulfolobus and Acidiplasma at the genus level.<br><br>CONCLUSIONS: Changes of fecal microbes may in part contribute to the anticancer or anti-depressant effects of RbCl. These findings further validate that the microbiome could be a target for therapeutic intervention.}, }
@article {pmid33585279, year = {2020}, author = {Tang, W and Meng, Z and Li, N and Liu, Y and Li, L and Chen, D and Yang, Y}, title = {Roles of Gut Microbiota in the Regulation of Hippocampal Plasticity, Inflammation, and Hippocampus-Dependent Behaviors.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {611014}, pmid = {33585279}, issn = {2235-2988}, mesh = {*Alzheimer Disease ; Animals ; *Gastrointestinal Microbiome ; Hippocampus ; Humans ; Inflammation ; Mice ; *Probiotics ; }, abstract = {The study of the gut microbiota-brain axis has become an intriguing field, attracting attention from both gastroenterologists and neurobiologists. The hippocampus is the center of learning and memory, and plays a pivotal role in neurodegenerative diseases, such as Alzheimer's disease (AD). Previous studies using diet administration, antibiotics, probiotics, prebiotics, germ-free mice, and fecal analysis of normal and specific pathogen-free animals have shown that the structure and function of the hippocampus are affected by the gut microbiota. Furthermore, hippocampal pathologies in AD are positively correlated with changes in specific microbiota. Genomic and neurochemical analyses revealed significant alterations in genes and amino acids in the hippocampus of AD subjects following a remarkable shift in the gut microbiota. In a recent study, when young animals were transplanted with fecal microbiota derived from AD patients, the recipients showed significant impairment of cognitive behaviors, AD pathologies, and changes in neuronal plasticity and cytokines. Other studies have demonstrated the side effects of antibiotic administration along with the beneficial effects of probiotics, prebiotics, and specific diets on the composition of the gut microbiota and hippocampal functions, but these have been mostly preliminary with unclear mechanisms. Since some specific gut bacteria are positively or negatively correlated to the structure and function of the hippocampus, it is expected that specific gut bacteria administration and other microbiota-based interventions could be potentially applied to prevent or treat hippocampus-based memory impairment and neuropsychiatric disorders such as AD.}, }
@article {pmid33580895, year = {2021}, author = {Wilmes, L and Collins, JM and O'Riordan, KJ and O'Mahony, SM and Cryan, JF and Clarke, G}, title = {Of bowels, brain and behavior: A role for the gut microbiota in psychiatric comorbidities in irritable bowel syndrome.}, journal = {Neurogastroenterology and motility}, volume = {33}, number = {3}, pages = {e14095}, doi = {10.1111/nmo.14095}, pmid = {33580895}, issn = {1365-2982}, mesh = {Anxiety Disorders/*microbiology/psychology ; *Brain ; Depressive Disorder/*microbiology/psychology ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*microbiology/psychology ; }, abstract = {BACKGROUND: The gastrointestinal microbiota has emerged as a key regulator of gut-brain axis signalling with important implications for neurogastroenterology. There is continuous bidirectional communication between the gut and the brain facilitated by neuronal, endocrine, metabolic, and immune pathways. The microbiota influences these signalling pathways via several mechanisms. Studies have shown compositional and functional alterations in the gut microbiota in stress-related psychiatric disorders. Gut microbiota reconfigurations are also a feature of irritable bowel syndrome (IBS), a gut-brain axis disorder sharing high levels of psychiatric comorbidity including both anxiety and depression. It remains unclear how the gut microbiota alterations in IBS align with both core symptoms and these psychiatric comorbidities.<br><br>METHODS: In this review, we highlight common and disparate features of these microbial signatures as well as the associated gut-brain axis signalling pathways. Studies suggest that patients with either IBS, depression or anxiety, alone or comorbid, present with alterations in gut microbiota composition and harbor immune, endocrine, and serotonergic system alterations relevant to the common pathophysiology of these comorbid conditions.<br><br>KEY RESULTS: Research has illustrated the utility of fecal microbiota transplantation in animal models, expanding the evidence base for a potential causal role of disorder-specific gut microbiota compositions in symptom set expression. Moreover, an exciting study by Constante and colleagues in this issue highlights the possibility of counteracting this microbiota-associated aberrant behavioral phenotype with a probiotic yeast, Saccharomyces boulardii CNCM I-745.<br><br>CONCLUSIONS AND INFERENCES: Such data highlights the potential for therapeutic targeting of the gut microbiota as a valuable strategy for the management of comorbid psychiatric symptoms in IBS.}, }
@article {pmid33579683, year = {2021}, author = {Warda, AK and Clooney, AG and Ryan, F and de Almeida Bettio, PH and Di Benedetto, G and Ross, RP and Hill, C}, title = {A postbiotic consisting of heat-treated lactobacilli has a bifidogenic effect in pure culture and in human fermented faecal communities.}, journal = {Applied and environmental microbiology}, volume = {87}, number = {8}, pages = {}, pmid = {33579683}, issn = {1098-5336}, abstract = {The gut microbiota has a significant impact on host health. Dietary interventions using probiotics, prebiotics and postbiotics have the potential to alter microbiota composition and function. Other therapeutic interventions such as antibiotics and faecal microbiota transplantation have also been shown to significantly alter the microbiota and its metabolites. Supplementation of a faecal fermentation model of the human gut with a postbiotic product Lactobacillus LB led to changes in microbiome composition (i.e. increase in beneficial bifidobacteria) and associated metabolic changes (i.e. increased acid production). Lactobacillus LB is a heat-treated preparation of cellular biomass and a fermentate generated by Limosilactobacillus fermentum CNCM MA65/4E-1b (formerly known as Lactobacillus fermentum CNCM MA65/4E-1b) and Lactobacillus delbrueckii ssp. delbrueckii CNCM MA65/4E-2z, medically relevant strains used to produce antidiarrheal preparations. In pure culture, Lactobacillus LB also stimulates the growth of a range of bifidobacterial species and strains. Lactobacillus LB-like preparations generated using other Lactobacillaceae, including commercially available probiotic bacteria, did not have the same impact on a model strain (Bifidobacterium longum subsp. infantis ATCC 15697). This bifidogenic activity is heat- and enzyme-stable and cannot be attributed to lactose, which is a major constituent of Lactobacillus LB. L fermentum CNCM MA65/4E-1b is largely responsible for the observed activity and there is a clear role for compounds smaller than 1 kDa.Importance In general, disruptions to the gut microbiota are associated with multiple disorders in humans. The presence of high levels of Bifidobacterium spp. in the human gut is commonly considered to be beneficial. Bifidobacteria can be supplemented in the diet (as probiotics) or those bifidobacteria already present in the gut can be stimulated by the consumption of prebiotics such as inulin. We demonstrate that Lactobacillus LB (a product consisting of two heat-killed lactic acid bacteria and their metabolites) can stimulate the growth of bifidobacteria in human fermented faecal communities and in pure culture. Given the heat-treatment applied during the production process, there is no risk of the lactic acid bacteria colonising (or causing bacteraemia) in vulnerable consumers (infants, immunocompromised, etc). Lactobacillus LB has the potential to affect human health by selectively promoting the growth of beneficial bacteria.}, }
@article {pmid33579424, year = {2021}, author = {Golonka, RM and Vijay-Kumar, M}, title = {Atypical immunometabolism and metabolic reprogramming in liver cancer: Deciphering the role of gut microbiome.}, journal = {Advances in cancer research}, volume = {149}, number = {}, pages = {171-255}, doi = {10.1016/bs.acr.2020.10.004}, pmid = {33579424}, issn = {2162-5557}, support = {R01 CA219144/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinoma, Hepatocellular/immunology/*metabolism/microbiology/*pathology ; *Gastrointestinal Microbiome ; Humans ; Immune System/immunology ; Liver Neoplasms/immunology/*metabolism/microbiology/*pathology ; }, abstract = {Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide. Much recent research has delved into understanding the underlying molecular mechanisms of HCC pathogenesis, which has revealed to be heterogenous and complex. Two major hallmarks of HCC include: (i) a hijacked immunometabolism and (ii) a reprogramming in metabolic processes. We posit that the gut microbiota is a third component in an entanglement triangle contributing to HCC progression. Besides metagenomic studies highlighting the diagnostic potential in the gut microbiota profile, recent research is pinpointing the gut microbiota as an instigator, not just a mere bystander, in HCC. In this chapter, we discuss mechanistic insights on atypical immunometabolism and metabolic reprogramming in HCC, including the examination of tumor-associated macrophages and neutrophils, tumor-infiltrating lymphocytes (e.g., T-cell exhaustion, regulatory T-cells, natural killer T-cells), the Warburg effect, rewiring of the tricarboxylic acid cycle, and glutamine addiction. We further discuss the potential involvement of the gut microbiota in these characteristics of hepatocarcinogenesis. An immediate highlight is that microbiota metabolites (e.g., short chain fatty acids, secondary bile acids) can impair anti-tumor responses, which aggravates HCC. Lastly, we describe the rising 'new era' of immunotherapies (e.g., immune checkpoint inhibitors, adoptive T-cell transfer) and discuss for the potential incorporation of gut microbiota targeted therapeutics (e.g., probiotics, fecal microbiota transplantation) to alleviate HCC. Altogether, this chapter invigorates for continuous research to decipher the role of gut microbiome in HCC from its influence on immunometabolism and metabolic reprogramming.}, }
@article {pmid33578974, year = {2021}, author = {Lee, JJ and Yong, D and Suk, KT and Kim, DJ and Woo, HJ and Lee, SS and Kim, BS}, title = {Alteration of Gut Microbiota in Carbapenem-Resistant Enterobacteriaceae Carriers during Fecal Microbiota Transplantation According to Decolonization Periods.}, journal = {Microorganisms}, volume = {9}, number = {2}, pages = {}, pmid = {33578974}, issn = {2076-2607}, support = {2019R1I1A3A01060465//Ministry of Education, Korea/ ; 2020R1A6A1A03043026//Ministry of Education, Korea/ ; NRF-2017M3A9F3043837//Ministry of Science, ICT and Future Planning/ ; HURF-2015-32//Hallym University/ ; }, abstract = {Fecal microbiota transplantation (FMT) has been suggested as an alternative therapeutic option to decolonize carbapenem-resistant Enterobacteriaceae (CRE). However, the analysis of gut microbiota alteration in CRE carriers during FMT is still limited. Here, gut microbiota changes in CRE carriers were evaluated during FMT according to decolonization periods. The decolonization of 10 CRE carriers was evaluated after FMT, using serial consecutive rectal swab cultures. Alterations of gut microbiota before and after FMT (56 serial samples) were analyzed using high-throughput sequencing. The decolonization rates of CRE carriers were 40%, 50%, and 90% within 1, 3 and 5 months after initial FMT, respectively. Gut microbiota significantly changed after FMT (p = 0.003). Microbiota alteration was different between the early decolonization carriers (EDC) and late decolonization carriers (LDC). Microbiota convergence in carriers to donors was detected in EDC within 4 weeks, and keystone genera within the Bacteroidetes were found in the gut microbiota of EDC before FMT. The relative abundance of Klebsiella was lower in EDC than in LDC, before and after FMT. Our results indicate that FMT is a potential option for CRE decolonization. The gut microbiota of CRE carriers could be used to predict decolonization timing after FMT, and determine repeated FMT necessity.}, }
@article {pmid33578830, year = {2021}, author = {Heo, G and Lee, Y and Im, E}, title = {Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer.}, journal = {Cancers}, volume = {13}, number = {4}, pages = {}, pmid = {33578830}, issn = {2072-6694}, support = {2019R1A2C1010536//National Research Foundation of Korea/ ; }, abstract = {Inflammatory mediators modulate inflammatory pathways during the development of colorectal cancer. Inflammatory mediators secreted by both immune and tumor cells can influence carcinogenesis, progression, and tumor metastasis. The gut microbiota, which colonize the entire intestinal tract, especially the colon, are closely linked to colorectal cancer through an association with inflammatory mediators such as tumor necrosis factor, nuclear factor kappa B, interleukins, and interferons. This association may be a potential therapeutic target, since therapeutic interventions targeting the gut microbiota have been actively investigated in both the laboratory and in clinics and include fecal microbiota transplantation and probiotics.}, }
@article {pmid33577875, year = {2021}, author = {Fujimoto, K and Kimura, Y and Allegretti, JR and Yamamoto, M and Zhang, YZ and Katayama, K and Tremmel, G and Kawaguchi, Y and Shimohigoshi, M and Hayashi, T and Uematsu, M and Yamaguchi, K and Furukawa, Y and Akiyama, Y and Yamaguchi, R and Crowe, SE and Ernst, PB and Miyano, S and Kiyono, H and Imoto, S and Uematsu, S}, title = {Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation.}, journal = {Gastroenterology}, volume = {160}, number = {6}, pages = {2089-2102.e12}, pmid = {33577875}, issn = {1528-0012}, support = {R01 AI079145/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteriophages ; Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Gastrointestinal Tract/*microbiology/virology ; Humans ; Male ; Metagenomics ; Microviridae ; Middle Aged ; Proteobacteria ; *Virome/genetics ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). However, the overall mechanisms underlying FMT success await comprehensive elucidation, and the safety of FMT has recently become a serious concern because of the occurrence of drug-resistant bacteremia transmitted by FMT. We investigated whether functional restoration of the bacteriomes and viromes by FMT could be an indicator of successful FMT.<br><br>METHODS: The human intestinal bacteriomes and viromes from 9 patients with rCDI who had undergone successful FMT and their donors were analyzed. Prophage-based and CRISPR spacer-based host bacteria-phage associations in samples from recipients before and after FMT and in donor samples were examined. The gene functions of intestinal microorganisms affected by FMT were evaluated.<br><br>RESULTS: Metagenomic sequencing of both the viromes and bacteriomes revealed that FMT does change the characteristics of intestinal bacteriomes and viromes in recipients after FMT compared with those before FMT. In particular, many Proteobacteria, the fecal abundance of which was high before FMT, were eliminated, and the proportion of Microviridae increased in recipients. Most temperate phages also behaved in parallel with the host bacteria that were altered by FMT. Furthermore, the identification of bacterial and viral gene functions before and after FMT revealed that some distinctive pathways, including fluorobenzoate degradation and secondary bile acid biosynthesis, were significantly represented.<br><br>CONCLUSIONS: The coordinated action of phages and their host bacteria restored the recipients' intestinal flora. These findings show that the restoration of intestinal microflora functions reflects the success of&#xa0;FMT.}, }
@article {pmid33576793, year = {2021}, author = {Ducarmon, QR and Kuijper, EJ and Olle, B}, title = {Opportunities and Challenges in Development of Live Biotherapeutic Products to Fight Infections.}, journal = {The Journal of infectious diseases}, volume = {223}, number = {12 Suppl 2}, pages = {S283-S289}, doi = {10.1093/infdis/jiaa779}, pmid = {33576793}, issn = {1537-6613}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Infections/prevention &amp; control/*therapy ; Biological Products/pharmacology/*therapeutic use ; *Drug Development ; Drug Resistance, Multiple, Bacterial/drug effects ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects ; Humans ; }, abstract = {Treatment of bacterial infections with broad-spectrum antibiotics is a strategy severely limited by the decreased ability of the perturbed resident microbiota to control expansion of antibiotic-resistant pathogens. Live biotherapeutic products (LBPs) could provide an alternative to antibiotics in infection control by restoring gut colonization resistance and controlling expansion of resistant strains, an important therapeutic need not being addressed with existing anti-infective drug modalities. We review opportunities and challenges in developing LBPs for multidrug-resistant organisms colonization and infection control, with a focus on commercial fecal microbiota transplantation-like products and defined bacterial consortia, and spanning considerations related to availability of models for rational drug candidate selection and dose regimen selection, good manufacturing practice, intellectual property, and commercial viability.}, }
@article {pmid33576711, year = {2021}, author = {Ahlawat, S and Kumar, P and Mohan, H and Goyal, S and Sharma, KK}, title = {Inflammatory bowel disease: tri-directional relationship between microbiota, immune system and intestinal epithelium.}, journal = {Critical reviews in microbiology}, volume = {47}, number = {2}, pages = {254-273}, doi = {10.1080/1040841X.2021.1876631}, pmid = {33576711}, issn = {1549-7828}, mesh = {Animals ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/immunology/microbiology ; Humans ; Immune System/immunology ; Inflammatory Bowel Diseases/immunology/*microbiology ; Intestinal Mucosa/immunology/*microbiology ; }, abstract = {Human gut microbiota contributes to host nutrition and metabolism, sustains intestinal cell proliferation and differentiation, and modulates host immune system. The alterations in their composition lead to severe gut disorders, including inflammatory bowel disease (IBD) or inflammatory bowel syndrome (IBS). IBD including ulcerative colitis (UC) and Crohn's disease (CD) are gamut of chronic inflammatory disorders of gut, mediated by complex interrelations among genetic, environmental, and internal factors. IBD has debateable aetiology, however in recent years, exploring the central role of a tri-directional relationship between gut microbiota, mucosal immune system, and intestinal epithelium in pathogenesis is getting the most attention. Increasing incidences and early onset explains the exponential rise in IBD burden on health-care systems. Industrialization, hypersensitivity to allergens, lifestyle, hygiene hypothesis, loss of intestinal worms, and gut microbial composition, explains this shifted rise. Hitherto, the interventions modulating gut microbiota composition, microfluidics-based in vitro gastrointestinal models, non-allergic functional foods, nutraceuticals, and faecal microbiota transplantation (FMT) from healthy donors are some of the futuristic approaches for the disease management.}, }
@article {pmid33575297, year = {2021}, author = {Saha, S and Khanna, S}, title = {Stool banking for fecal microbiota transplantation: ready for prime time?.}, journal = {Hepatobiliary surgery and nutrition}, volume = {10}, number = {1}, pages = {110-112}, pmid = {33575297}, issn = {2304-3881}, }
@article {pmid33575288, year = {2021}, author = {Sheng, L and Jena, PK and Hu, Y and Wan, YY}, title = {Age-specific microbiota in altering host inflammatory and metabolic signaling as well as metabolome based on the sex.}, journal = {Hepatobiliary surgery and nutrition}, volume = {10}, number = {1}, pages = {31-48}, pmid = {33575288}, issn = {2304-3881}, support = {R01 CA222490/CA/NCI NIH HHS/United States ; U01 CA179582/CA/NCI NIH HHS/United States ; U2C DK092993/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Metabolism is sex-different, and the direct link between gut microbiota and aging-associated metabolic changes needs to be established in both sexes.<br><br>METHODS: Gene expression, metabolic and inflammatory signaling, gut microbiota profile, and metabolome were studied during aging and after fecal microbiota transplantation (FMT) in mice of both sexes.<br><br>RESULTS: Our data revealed young female mice and aged male mice were the most insulin sensitive and resistant group, respectively. In addition, aging reduced sex difference in insulin sensitivity. Such age- and sex-dependent metabolic phenotypes were accompanied by shifted gut microbiota profile and altered abundance of bacterial genes that produce butyrate, propionate, and bile acids. After receiving feces from the aged males (AFMT), the most insulin-resistant group, recipients of both sexes had increased hepatic inflammation and serum endotoxin. However, AFMT only increased insulin resistance in female mice and abolished sex difference in insulin sensitivity. Additionally, such changes were accompanied by narrowed sex difference in metabolome. Metabolomics data revealed that age-associated insulin resistance in males was accompanied by increased sugar alcohols and dicarboxylic acids as well as reduced aromatic and branched-chain amino acids. Further, receiving feces from the young females (YFMT), the most insulin-sensitive group, reduced body weight and fasting blood glucose in male recipients and improved insulin sensitivity in females, leading to enhanced sex differences in insulin sensitivity and metabolome.<br><br>CONCLUSIONS: Aging systemically affected inflammatory and metabolic signaling based on the sex. Gut microbiome is age and sex-specific, which affects inflammation and metabolism in a sex-dependent manner.}, }
@article {pmid33574587, year = {2021}, author = {Mullard, A}, title = {Faecal matter transplants boost immuno-oncology efficacy.}, journal = {Nature reviews. Drug discovery}, volume = {20}, number = {3}, pages = {166}, doi = {10.1038/d41573-021-00029-3}, pmid = {33574587}, issn = {1474-1784}, }
@article {pmid33573867, year = {2021}, author = {Ciernikova, S and Kasperova, B and Drgona, L and Smolkova, B and Stevurkova, V and Mego, M}, title = {Targeting the gut microbiome: An emerging trend in hematopoietic stem cell transplantation.}, journal = {Blood reviews}, volume = {48}, number = {}, pages = {100790}, doi = {10.1016/j.blre.2020.100790}, pmid = {33573867}, issn = {1532-1681}, mesh = {Biodiversity ; Combined Modality Therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/immunology/radiation effects ; Graft vs Host Disease/etiology/mortality/prevention &amp; control ; Hematologic Neoplasms/complications/therapy ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Humans ; Prognosis ; Transplantation Conditioning/adverse effects/methods ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {Mounting evidence has demonstrated the critical role of the gut microbiome in different cancer treatment modalities showing intensive crosstalk between microbiota and the host immune system. In cancer patients receiving hematopoietic stem cell transplantation (HSCT), conditioning regimens including chemotherapy, radiotherapy, and immunosuppressive therapy, as well as antimicrobial prophylaxis, result in intestinal barrier disruption and massive changes in microbiota composition. According to clinical studies, a drastic loss of microbial diversity during HSCT is associated with enhanced pro-inflammatory immune response and an increased risk of transplant-related complications such as graft-versus-host disease (GvHD) and mortality. In this review, we outline the current understanding of the role of microbiota diversity in the patient response to cancer therapies and highlight the impact of changes in the gut microbiome on clinical outcomes in post-HSCT patients. Moreover, the therapeutic implications of microbiota modulation by probiotics, prebiotics, and fecal microbiota transplantation (FMT) in hematologic cancer patients receiving HSCT are discussed.}, }
@article {pmid33572016, year = {2021}, author = {Chauhan, A and Apostolov, R and van Langenberg, D and Garg, M}, title = {Faecal microbiota transplantation for recurrent Clostridioides difficile infection: an Australian experience - effective, safe, yet room for improvement.}, journal = {Internal medicine journal}, volume = {51}, number = {1}, pages = {106-110}, doi = {10.1111/imj.15162}, pmid = {33572016}, issn = {1445-5994}, mesh = {Australia ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) is reportedly effective and safe for the management of recurrent or refractory Clostridioides difficile infection (CDI), yet real-world data of outcomes of FMT in Australia are limited. In this series, FMT safely resulted in resolution of CDI in 19 patients with reduced healthcare utilisation after 25 FMT, but one patient was diagnosed with an anti-nuclear antibody-positive constitutional illness and Hashimoto thyroiditis following FMT. Further prospective evaluation of the utility of FMT earlier in CDI treatment algorithms to minimise cost and morbidity, and recipient follow up for immune-mediated conditions, is required.}, }
@article {pmid33571456, year = {2021}, author = {Ianiro, G and Mullish, BH and Hvas, CL and Segal, JP and Kuijper, EJ and Costello, SP and Kelly, CR and Allegretti, JR and Fischer, M and Iqbal, TH and Satokari, R and Kao, D and van Prehn, J and Ng, SC and Bibbò, S and Baunwall, SMD and Quraishi, MN and Sokol, H and Zhang, F and Keller, J and Masucci, L and Quaranta, G and Kassam, Z and Sanguinetti, M and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {SARS-CoV-2 vaccines and donor recruitment for FMT.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {6}, number = {4}, pages = {264-266}, pmid = {33571456}, issn = {2468-1253}, mesh = {COVID-19/*prevention &amp; control/transmission ; *COVID-19 Vaccines ; Donor Selection/*organization &amp; administration ; *Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid33571442, year = {2021}, author = {Rebeck, ON and Dantas, G and Schwartz, DJ}, title = {Improving ICI outcomes with a little help from my microbial friends.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {2}, pages = {155-157}, doi = {10.1016/j.chom.2021.01.012}, pmid = {33571442}, issn = {1934-6069}, mesh = {Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Neoplasms/*drug therapy ; Programmed Cell Death 1 Receptor/*antagonists &amp; inhibitors ; }, abstract = {Gut microbiome composition correlates with responsiveness to immune checkpoint inhibitor therapy. In a recent study in Science, Baruch et al. manipulated gut microbiome composition in patients with refractory metastatic melanoma using fecal microbiota transplants. Fecal microbiota transplant was safe and partially effective in inducing remission in refractory patients.}, }
@article {pmid33571438, year = {2021}, author = {Benech, N and Rolhion, N and Sokol, H}, title = {Tryptophan metabolites get the gut moving.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {2}, pages = {145-147}, doi = {10.1016/j.chom.2021.01.009}, pmid = {33571438}, issn = {1934-6069}, mesh = {Bacteria ; *Enteric Nervous System ; Enteroendocrine Cells ; *Gastrointestinal Microbiome ; Tryptophan ; }, abstract = {How gut microbes can regulate the enteric nervous system and gut-brain communications is a field of intense research. In this issue of Cell Host &amp; Microbe, Ye et al. demonstrate that bacteria can control intestinal motility and vagal neuronal activation via tryptophan catabolites through the receptor TrpA1 of enteroendocrine cells.}, }
@article {pmid33570405, year = {2021}, author = {Huang, Y and Yang, Q and Mi, X and Qiu, L and Tao, X and Zhang, Z and Xia, J and Wu, Q and Wei, H}, title = {Ripened Pu-erh Tea Extract Promotes Gut Microbiota Resilience against Dextran Sulfate Sodium Induced Colitis.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {7}, pages = {2190-2203}, doi = {10.1021/acs.jafc.0c07537}, pmid = {33570405}, issn = {1520-5118}, mesh = {Animals ; *Colitis/chemically induced/drug therapy ; Dextran Sulfate/toxicity ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Plant Extracts ; RNA, Ribosomal, 16S/genetics ; Tea ; }, abstract = {Ripened Pu-erh tea (RPT) has been shown to be an effective natural ingredient to defend against experimentally induced colitis. We hypothesized that RPT would alleviate dextran sulfate sodium (DSS) induced colitis via modulating intestinal microbiota. The effect of RPT on mice gut microbiota was evaluated using 16S rRNA gene amplicon sequencing, broad-spectrum antibiotic (ABX) treatment, and fecal microbiota transplantation (FMT). Pretreatment with RPT enhanced intestinal barrier function, reduced colonic and serum proinflammatory cytokine and macrophage infiltration, and preserved the resilience of gut microbiota in mice during a DSS challenge. Administration of either RPT-regulated or healthy control-derived gut microbiota showed similar protection against colitis, and such protection could not be recapitulated with fecal microbiota from ABX-treated mice, suggesting a key role of protective consortium in the disease protection. Mechanistically, cecal contents of short-chain fatty acids (SCFAs) and colonic peroxisome proliferator activated receptor-γ (PPAR-γ) expression in colitis mice increased significantly by RPT intervention. Collectively, RPT treatment improved DSS-induced colitis by partially reversing the dysbiosis state of gut microbiota, which might be associated with an increase in SCFA level and PPAR-γ expression.}, }
@article {pmid33569665, year = {2022}, author = {Wada, A and Higashiyama, M and Kurihara, C and Ito, S and Tanemoto, R and Mizoguchi, A and Nishii, S and Inaba, K and Sugihara, N and Hanawa, Y and Horiuchi, K and Shibuya, N and Akiyama, M and Okada, Y and Watanabe, C and Komoto, S and Tomita, K and Takei, F and Hokari, R}, title = {Protective Effect of Luminal Uric Acid Against Indomethacin-Induced Enteropathy: Role of Antioxidant Effect and Gut Microbiota.}, journal = {Digestive diseases and sciences}, volume = {67}, number = {1}, pages = {121-133}, pmid = {33569665}, issn = {1573-2568}, mesh = {Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Antioxidants/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome/drug effects/immunology ; Indomethacin/*pharmacology ; Intestinal Diseases/chemically induced/metabolism/microbiology/therapy ; *Intestine, Small/metabolism/microbiology ; Mice ; Oxidative Stress/drug effects ; Protective Factors ; Reactive Oxygen Species/analysis ; Treatment Outcome ; *Uric Acid/blood/metabolism ; }, abstract = {BACKGROUND: Uric acid (UA) has anti- and pro-inflammatory properties. We previously revealed that elevated serum UA levels provide protection against murine small intestinal injury probably via luminal UA secreted in the small intestine. Luminal UA may act as an antioxidant, preventing microbiota vulnerability to oxidative stress. However, whether luminal UA is increased under hyperuricemia and plays a protective role in a dose-dependent manner as well as the mechanism by which luminal UA exerts its protective effects on enteropathy remains unknown.<br><br>METHODS: Inosinic acid (IMP) (1000&#xa0;mg/kg, i.p.) was administered to obtain high serum UA (HUA) and moderate serum UA (500&#xa0;mg/kg IMP, i.p.) mice. UA concentrations and levels of oxidative stress markers in the serum and intestine were measured. Mice received indomethacin (20&#xa0;mg/kg, i.p.) to evaluate the effects of UA on indomethacin-induced enteropathy. Reactive oxygen species (ROS) on the ileal mucosa were analyzed. The fecal microbiota of HUA mice was transplanted to investigate its effect on indomethacin-induced enteropathy.<br><br>RESULTS: IMP increased luminal UA dose-dependently, with higher levels of luminal antioxidant markers. Indomethacin-induced enteropathy was significantly ameliorated in both UA-elevated groups, with decreased indomethacin-induced luminal ROS. The microbiota of HUA mice showed a significant increase in &#x3b1;-diversity and a significant difference in &#x3b2;-diversity from the control. Fecal microbiota transplantation from HUA mice ameliorated indomethacin-induced enteropathy.<br><br>CONCLUSIONS: The protective role of luminal UA in intestinal injury is likely exerted via oxidative stress elimination and microbiota composition modulation, preferably for gut immunity. Therefore, enhancing anaerobic conditions using antioxidants is a potential therapeutic target.}, }
@article {pmid33568354, year = {2021}, author = {}, title = {Stool Swap Overcomes PD-1 Resistance.}, journal = {Cancer discovery}, volume = {11}, number = {5}, pages = {1000-1001}, doi = {10.1158/2159-8290.CD-NB2021-0311}, pmid = {33568354}, issn = {2159-8290}, abstract = {Fecal transplants can make immunotherapy-refractory melanomas sensitive to checkpoint blockade, a finding that highlights the potential of manipulating gut bacteria to boost response rates to anti-PD-1 agents. Yet, how best to modulate the microbiome remains a matter of active debate.}, }
@article {pmid33567176, year = {2021}, author = {Janket, SJ and Conte, HA and Diamandis, EP}, title = {Inappropriate extrapolations abound in fecal microbiota research.}, journal = {Clinical chemistry and laboratory medicine}, volume = {59}, number = {7}, pages = {e307-e308}, doi = {10.1515/cclm-2020-1862}, pmid = {33567176}, issn = {1437-4331}, mesh = {Feces ; Humans ; *Microbiota ; }, }
@article {pmid33564705, year = {2020}, author = {Gouveia, C and Palos, C and Pereira, P and Roque Ramos, L and Cravo, M}, title = {Fecal Microbiota Transplant in a Patient Infected with Multidrug-Resistant Bacteria: A Case Report.}, journal = {GE Portuguese journal of gastroenterology}, volume = {28}, number = {1}, pages = {56-61}, pmid = {33564705}, issn = {2341-4545}, abstract = {INTRODUCTION: There has been a growing interest in fecal microbiota transplantation (FMT) as a way to manipulate gut microbiota, with potential benefit in patients infected with multidrug-resistant (MDR) bacteria.<br><br>CASE PRESENTATION: We present the case of an 87-year-old male with recurrent ascending cholangitis due to biliary atony and impaired biliary drainage after multiple biliary sphincterotomies and two papillary balloon dilations. In this context, a choledochoduodenostomy was performed, but the patient kept on having repeated episodes of acute cholangitis, resulting in multiple hospitalizations, every other week, with need of multiple broad-spectrum antibiotic courses, which led to bacteremias with MDR microorganisms. Several therapeutic strategies such as prophylactic antibiotics (including rifaximin), pre- and probiotics, prokinetics, and ursodeoxycholic acid were unsuccessfully attempted. After multidisciplinary case discussion, an FMT was proposed, with the aim of manipulating gut microbiota and decreasing MDR bacteremias. We first performed FMT via colonoscopy in September 2018, after which the patient still had 3 more hospitalizations for acute cholangitis, but isolated bacteria in blood cultures were resistant only to amoxicillin and clavulanic acid. Considering this apparent change in the microbial resistance profile, we performed a second FMT in January 2019 via the upper gastrointestinal route. During the next 4 months, the patient remained well. In April 2019, the patient relapsed again with three more episodes of cholangitis, for which we repeated the FMT via upper gastrointestinal endoscopy. No readmissions were observed during the next 4 months. All three FMTs were performed without complications.<br><br>DISCUSSION AND CONCLUSION: FMT seems to be a safe procedure and was effective in decreasing hospital admissions and changing the profile of MDR bacteria previously isolated from blood cultures.}, }
@article {pmid33563544, year = {2021}, author = {Liwinski, T and Leshem, A and Elinav, E}, title = {Breakthroughs and Bottlenecks in Microbiome Research.}, journal = {Trends in molecular medicine}, volume = {27}, number = {4}, pages = {298-301}, doi = {10.1016/j.molmed.2021.01.003}, pmid = {33563544}, issn = {1471-499X}, mesh = {Diet ; Fecal Microbiota Transplantation ; Host Microbial Interactions ; Humans ; Metagenomics/methods ; *Microbiota/drug effects/genetics/immunology ; Phage Therapy ; Precision Medicine/trends ; Probiotics ; }, abstract = {Over the past 15 years, the research community has witnessed unprecedented progress in microbiome research. We review this increasing knowledge and first attempts of its clinical application, and also limitations and challenges faced by the research community, in mechanistically understanding host-microbiome interactions and integrating these insights into clinical practice.}, }
@article {pmid33562721, year = {2021}, author = {Banfi, D and Moro, E and Bosi, A and Bistoletti, M and Cerantola, S and Crema, F and Maggi, F and Giron, MC and Giaroni, C and Baj, A}, title = {Impact of Microbial Metabolites on Microbiota-Gut-Brain Axis in Inflammatory Bowel Disease.}, journal = {International journal of molecular sciences}, volume = {22}, number = {4}, pages = {}, pmid = {33562721}, issn = {1422-0067}, mesh = {Anti-Inflammatory Agents/therapeutic use ; Bacteria/*chemistry/immunology ; Bile Acids and Salts/metabolism ; Brain/*metabolism ; Dysbiosis ; Fatty Acids, Volatile/metabolism ; Gastrointestinal Tract/*microbiology ; Humans ; Inflammatory Bowel Diseases/*drug therapy/microbiology/psychology ; Severity of Illness Index ; Tryptophan/metabolism ; }, abstract = {The complex bidirectional communication system existing between the gastrointestinal tract and the brain initially termed the "gut-brain axis" and renamed the "microbiota-gut-brain axis", considering the pivotal role of gut microbiota in sustaining local and systemic homeostasis, has a fundamental role in the pathogenesis of Inflammatory Bowel Disease (IBD). The integration of signals deriving from the host neuronal, immune, and endocrine systems with signals deriving from the microbiota may influence the development of the local inflammatory injury and impacts also more distal brain regions, underlying the psychophysiological vulnerability of IBD patients. Mood disorders and increased response to stress are frequently associated with IBD and may affect the disease recurrence and severity, thus requiring an appropriate therapeutic approach in addition to conventional anti-inflammatory treatments. This review highlights the more recent evidence suggesting that alterations of the microbiota-gut-brain bidirectional communication axis may concur to IBD pathogenesis and sustain the development of both local and CNS symptoms. The participation of the main microbial-derived metabolites, also defined as "postbiotics", such as bile acids, short-chain fatty acids, and tryptophan metabolites in the development of IBD-associated gut and brain dysfunction will be discussed. The last section covers a critical evaluation of the main clinical evidence pointing to the microbiome-based therapeutic approaches for the treatment of IBD-related gastrointestinal and neuropsychiatric symptoms.}, }
@article {pmid33561650, year = {2021}, author = {Huang, W and Kong, D}, title = {The intestinal microbiota as a therapeutic target in the treatment of NAFLD and ALD.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {135}, number = {}, pages = {111235}, doi = {10.1016/j.biopha.2021.111235}, pmid = {33561650}, issn = {1950-6007}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bacteria/drug effects/*metabolism ; Diet, Healthy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Humans ; Intestines/*microbiology ; Liver/*metabolism/pathology ; Liver Diseases, Alcoholic/metabolism/*microbiology/pathology/therapy ; Non-alcoholic Fatty Liver Disease/metabolism/*microbiology/pathology/therapy ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {Liver diseases are currently common disorders worldwide. Especially, the proportion of patients with nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) is growing globally. An increasing number of studies have revealed a close relationship between the intestinal microbiota and the development of NAFLD and ALD. A better understanding of the role of intestinal microbiota and the intestine-liver axis thus might lead to the development novel therapies for the treatment of these diseases.}, }
@article {pmid33561397, year = {2021}, author = {Simpson, RC and Shanahan, E and Scolyer, RA and Long, GV}, title = {Targeting the Microbiome to Overcome Resistance.}, journal = {Cancer cell}, volume = {39}, number = {2}, pages = {151-153}, doi = {10.1016/j.ccell.2021.01.016}, pmid = {33561397}, issn = {1878-3686}, mesh = {Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; *Melanoma/drug therapy/genetics ; *Microbiota ; }, abstract = {Immune checkpoint inhibition has revolutionized the treatment of many cancers, including melanoma. However, primary and acquired resistance remain key challenges for the field. Promising results from a phase I clinical trial recently published in Science highlight the potential of modulating the microbiome via fecal transplant to overcome resistance to immunotherapy.}, }
@article {pmid33558654, year = {2021}, author = {Zhang, JD and Liu, J and Zhu, SW and Fang, Y and Wang, B and Jia, Q and Hao, HF and Kao, JY and He, QH and Song, LJ and Liu, F and Zhu, BL and Owyang, C and Duan, LP}, title = {Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation.}, journal = {Acta pharmacologica Sinica}, volume = {42}, number = {11}, pages = {1821-1833}, pmid = {33558654}, issn = {1745-7254}, support = {P30 DK034933/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Berberine/pharmacology/*therapeutic use ; Brain-Gut Axis/*drug effects/physiology ; Cell Line ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Irritable Bowel Syndrome/drug therapy/metabolism ; Male ; Mice ; Microglia/*drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord/*drug effects/metabolism ; Stress, Psychological/drug therapy/metabolism ; Visceral Pain/*drug therapy/metabolism ; }, abstract = {Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg[-1] ·d[-1], ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg[-1] ·d[-1], ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota-gut-brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.}, }
@article {pmid33557941, year = {2021}, author = {Liu, F and Ye, S and Zhu, X and He, X and Wang, S and Li, Y and Lin, J and Wang, J and Lin, Y and Ren, X and Li, Y and Deng, Z}, title = {Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients.}, journal = {Journal of medical case reports}, volume = {15}, number = {1}, pages = {60}, pmid = {33557941}, issn = {1752-1947}, support = {81970156//National Natural Science foundation of China/ ; 81970118//National Natural Science foundation of China/ ; }, mesh = {Aged ; *B-Lymphocyte Subsets ; Bacteroidetes ; Bifidobacterium ; COVID-19/*complications/immunology ; Dysbiosis/microbiology/*therapy ; Faecalibacterium ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Diseases/microbiology/*therapy ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Patient Discharge ; Proteobacteria ; SARS-CoV-2 ; Young Adult ; }, abstract = {BACKGROUND: To investigate the potential beneficial effect of fecal microbiota transplantation (FMT) on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients.<br><br>CASE PRESENTATION: A total of 11 COVID-19 patients were recruited in April, 2020, about one month on average after they were discharged from the hospital. All subjects received FMT for 4 consecutive days by oral capsule administrations with 10 capsules for each day. In total, 5 out of 11 patients reported to be suffered from gastrointestinal symptoms, which were improved after FMT. After FMT, alterations of B cells were observed, which was characterized as decreased naive B cell (P&#x2009;=&#x2009;0.012) and increased memory B cells (P&#x2009;=&#x2009;0.001) and non-switched B cells (P&#x2009;=&#x2009;0.012).The microbial community richness indicated by operational taxonomic units number, observed species and Chao1 estimator was marginally increased after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteria (9.2%). FMT can partially restore the gut dysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteria (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium had significantly increased after FMT.<br><br>CONCLUSIONS: After FMT, altered peripheral lymphocyte subset, restored gut microbiota and alleviated gastrointestinal disorders were observe, suggesting that FMT may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.}, }
@article {pmid33557125, year = {2021}, author = {Pession, A and Zama, D and Muratore, E and Leardini, D and Gori, D and Guaraldi, F and Prete, A and Turroni, S and Brigidi, P and Masetti, R}, title = {Fecal Microbiota Transplantation in Allogeneic Hematopoietic Stem Cell Transplantation Recipients: A Systematic Review.}, journal = {Journal of personalized medicine}, volume = {11}, number = {2}, pages = {}, pmid = {33557125}, issn = {2075-4426}, support = {GR-2013-02357136//Ministero della Salute/ ; }, abstract = {The disruption of gut microbiota eubiosis has been linked to major complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Various strategies have been developed to reduce dysbiosis and related complications. Fecal microbiota transplantation (FMT) consists of the infusion of fecal matter from a healthy donor to restore impaired intestinal homeostasis, and could be applied in the allo-HSCT setting. We conducted a systematic review of studies addressing the use of FMT in allo-HSCT patients. In the 23 papers included in the qualitative synthesis, FMT was used for the treatment of recurrent Clostridioides difficile infections or as a therapeutic strategy for steroid-resistant gut aGvHD. FMT was also performed with a preventive aim (e.g., to decolonize from antibiotic-resistant bacteria). Additional knowledge on the biological mechanisms underlying clinical findings is needed in order to employ FMT in clinical practice. There is also concern regarding the administration of microbial consortia in immune-compromised patients with altered gut permeability. Therefore, the safety profile and efficacy of the procedure must be determined to better assess the role of FMT in allo-HSCT recipients.}, }
@article {pmid33557031, year = {2021}, author = {Gawlik-Kotelnicka, O and Strzelecki, D}, title = {Adiposity in Depression or Depression in Adiposity? The Role of Immune-Inflammatory-Microbial Overlap.}, journal = {Life (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {33557031}, issn = {2075-1729}, abstract = {Some of the most common and debilitating conditions are metabolic disorders (metabolic syndrome and non-alcoholic fatty liver disease) and depression. These conditions are also exacerbated by the fact that they often co-occur. Although the exact mechanisms underlying such relationships are poorly known, antipsychotic medication and antidepressant use, diet and physical activity, and lifestyle factors are believed to play a role; however, their high co-occurrence rate suggests a possible pathophysiological overlap. This paper reviews several possible bases for this overlap, including hypothalamic-pituitary-adrenal axis dysregulation, immune alterations with chronic inflammation, and oxidative stress. While it is entirely possible that changes in the microbiota may play a role in each of them, interventions based on the implementation of dietary and other lifestyle changes, supplementation with prebiotics or probiotics and faecal microbiota transplantation have failed to achieve conclusive results. A better characterization of the above associations may allow a more targeted approach to the treatment of both depressive and metabolic disorders. The paper also presents several practical applications for future studies.}, }
@article {pmid33556916, year = {2021}, author = {Wu, L and Yan, Q and Chen, F and Cao, C and Wang, S}, title = {Bupleuri radix extract ameliorates impaired lipid metabolism in high-fat diet-induced obese mice via gut microbia-mediated regulation of FGF21 signaling pathway.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {135}, number = {}, pages = {111187}, doi = {10.1016/j.biopha.2020.111187}, pmid = {33556916}, issn = {1950-6007}, mesh = {Adipose Tissue, White/*drug effects/metabolism ; Animals ; Anti-Obesity Agents/isolation &amp; purification/*pharmacology ; Bacteria/growth &amp; development/*metabolism ; *Bupleurum/chemistry ; Diet, High-Fat ; Disease Models, Animal ; Fibroblast Growth Factors/*metabolism ; *Gastrointestinal Microbiome ; Intestines/*microbiology ; Lipid Metabolism/*drug effects ; Liver/*drug effects/metabolism ; Male ; Mice, Inbred C57BL ; Obesity/*drug therapy/metabolism/microbiology ; Plant Extracts/isolation &amp; purification/*pharmacology ; Plant Roots ; Signal Transduction ; Mice ; }, abstract = {BACKGROUND: Obesity and its comorbidities are associated with abnormal lipid metabolism and gut microbiota dysbiosis. Bupleuri Radix is a medicinal plant used in traditional Chinese medicine with the prevention and treatment of obesity-related diseases. In this study, we aim to validate the regulation of Bupleuri Radix Extract (BupE) on lipid metabolism in obese mice, and try to find out the potential active components and reveal the underlying mechanisms.<br><br>METHODS: Ingredients in BupE, their circulating metabolites in mice and fecal biotransformation products were analyzed by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). Western blotting, RT-PCR and ELISA were used for tests of objective genes and proteins. 16&#x2009;s rRNA sequencing was performed to examine intestinal bacteria composition and microbes' functional changes were predicted with PICRUSt software. An absolute quantification method was set up via the construction of recombinant plasmid for the assays of intestinal flora. Specific microbial strains were cultured in anaerobic conditions and oral administrated to mice for intestinal mono-colonization.<br><br>RESULTS: BupE attenuated obesity, liver steatosis, and dyslipidemia in HFD-fed mice by up-regulating the expression of FGF21 in liver and white adipose tissue (WAT) as well as the downstream proteins of FGF21 signal pathway including &#x3b2;-klotho, GLUT1 and PGC-1&#x3b1;, etc. UPLC/Q-TOF-MS fingerprints showed no compounds from BupE or their metabolites or biotransformation products were detected in rodent serum samples. High-throughput pyrosequencing data indicated that BupE reversed obesity-induced constructional and functional alterations of intestinal flora. Two bacterial strains, Bacteroides acidifaciens (B. acidifaciens) and Ruminococcus gnavus (R. gnavus), were separated and identified from the feces of obese mice and by intestinal mono-colonization they were verified to intervene in the anti-obesity effects of BupE on mice.<br><br>CONCLUSION: These data suggest that BupE protects against diet-induced obesity and counteracts metabolic syndrome features consistent with a mechanism involving the gut-liver axis that boosts hepatic FGF21 secretion and consequent down-stream proteins expression relating to lipid metabolism. And in this gut-liver axis, intestinal microbes such as B.acidifaciens and R.gnavus play an indispensable role.}, }
@article {pmid33556154, year = {2021}, author = {Jung, HJ and Sorbara, MT and Pamer, EG}, title = {TAM mediates adaptation of carbapenem-resistant Klebsiella pneumoniae to antimicrobial stress during host colonization and infection.}, journal = {PLoS pathogens}, volume = {17}, number = {2}, pages = {e1009309}, pmid = {33556154}, issn = {1553-7374}, support = {P41 GM108569/GM/NIGMS NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; S10 OD025194/OD/NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; }, mesh = {*Adaptation, Physiological ; Animals ; Anti-Bacterial Agents/*pharmacology ; Bacterial Outer Membrane Proteins/genetics/*metabolism ; Carbapenem-Resistant Enterobacteriaceae/*drug effects ; Carbapenems/pharmacology ; Cell Membrane Permeability ; Female ; Klebsiella Infections/*drug therapy/genetics/metabolism/microbiology ; Klebsiella pneumoniae/*drug effects ; Mice ; Mice, Inbred C57BL ; Proteome/*metabolism ; Stress, Physiological ; }, abstract = {Gram-negative pathogens, such as Klebsiella pneumoniae, remodel their outer membrane (OM) in response to stress to maintain its integrity as an effective barrier and thus to promote their survival in the host. The emergence of carbapenem-resistant K. pneumoniae (CR-Kp) strains that are resistant to virtually all antibiotics is an increasing clinical problem and OM impermeability has limited development of antimicrobial agents because higher molecular weight antibiotics cannot access sites of activity. Here, we demonstrate that TAM (translocation and assembly module) deletion increases CR-Kp OM permeability under stress conditions and enhances sensitivity to high-molecular weight antimicrobials. SILAC-based proteomic analyses revealed mis-localization of membrane proteins in the TAM deficient strain. Stress-induced sensitization enhances clearance of TAM-deficient CR-Kp from the gut lumen following fecal microbiota transplantation and from infection sites following pulmonary or systemic infection. Our study suggests that TAM, as a regulator of OM permeability, represents a potential target for development of agents that enhance the effectiveness of existing antibiotics.}, }
@article {pmid33554953, year = {2021}, author = {Sofi, MH and Wu, Y and Ticer, T and Schutt, S and Bastian, D and Choi, HJ and Tian, L and Mealer, C and Liu, C and Westwater, C and Armeson, KE and Alekseyenko, AV and Yu, XZ}, title = {A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD.}, journal = {JCI insight}, volume = {6}, number = {3}, pages = {}, pmid = {33554953}, issn = {2379-3708}, support = {R01 AI135631/AI/NIAID NIH HHS/United States ; U54 CA210962/CA/NCI NIH HHS/United States ; U54 CA210963/CA/NCI NIH HHS/United States ; P20 GM130457/GM/NIGMS NIH HHS/United States ; R01 HL140953/HL/NHLBI NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; R01 HL137373/HL/NHLBI NIH HHS/United States ; T32 DK124191/DK/NIDDK NIH HHS/United States ; P30 DK123704/DK/NIDDK NIH HHS/United States ; R01 AI118305/AI/NIAID NIH HHS/United States ; }, mesh = {Allografts ; Animals ; Bacteroides fragilis/*immunology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Graft vs Host Disease/immunology/microbiology/*prevention &amp; control ; Graft vs Leukemia Effect/immunology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Isoantigens/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred DBA ; T-Lymphocytes/immunology ; Tumor Cells, Cultured ; }, abstract = {Graft-versus-host disease (GVHD) is a pathological process caused by an exaggerated donor lymphocyte response to host antigens after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T cells undergo extensive clonal expansion and differentiation, which culminate in damage to recipient target organs. Damage to the gastrointestinal tract is a main contributor to morbidity and mortality. The loss of diversity among intestinal bacteria caused by pretransplant conditioning regimens leads to an outgrowth of opportunistic pathogens and exacerbated GVHD after allo-HCT. Using murine models of allo-HCT, we found that an increase of Bacteroides in the intestinal microbiota of the recipients was associated with reduced GVHD in mice given fecal microbial transplantation. Administration of Bacteroides fragilis through oral gavage increased gut microbiota diversity and beneficial commensal bacteria and significantly ameliorated acute and chronic GVHD development. Preservation of gut integrity following B. fragilis exposure was likely attributed to increased short chain fatty acids, IL-22, and regulatory T cells, which in turn improved gut tight junction integrity and reduced inflammatory cytokine production of pathogenic T cells. The current study provides a proof of concept that a single strain of commensal bacteria can be a safe and effective means to protect gut integrity and ameliorate GVHD after allo-HCT.}, }
@article {pmid33554105, year = {2021}, author = {Jeevarathinam, AS and Guo, F and Williams, T and Smolen, JA and Hyde, JA and McShane, MJ and de Figueiredo, P and Alge, DL}, title = {Enzyme functionalized microgels enable precise regulation of dissolved oxygen and anaerobe culture.}, journal = {Materials today. Bio}, volume = {9}, number = {}, pages = {100092}, pmid = {33554105}, issn = {2590-0064}, abstract = {Anaerobes are a major constituent of the gut microbiome and profoundly influence the overall health of humans. However, the lack of a simple, cost-effective, and scalable system that mimics the anaerobic conditions of the human gut is hindering research on the gut microbiome and the development of therapeutics. Here, we address this gap by using glucose oxidase and catalase containing gelatin microparticles (GOx-CAT-GMPs) to precisely regulate dissolved oxygen concentration [O2] via GOx-mediated consumption of oxygen. Fluorescence images generated using conjugated polymer afterglow nanoparticles showed that [O2] can be tuned from 257.9 ± 6.2 to 0.0 ± 4.0 μM using GOx-CAT-GMPs. Moreover, when the obligate anaerobe Bacteroides thetaiotaomicron was inoculated in media containing GOx-CAT-GMPs, bacterial growth under ambient oxygen was comparable to control conditions in an anaerobic chamber (5.4 × 10[5] and 8.8 × 10[5] colony forming units mL[-1], respectively). Finally, incorporating GOx-CAT-GMPs into a bioreactor that permitted continuous radial diffusion of oxygen and glucose generated a gut-mimetic [O2] gradient of 132.4 ± 2.6 μM in the outer ring of the reactor to 7.9 ± 1.7 μM at the core. Collectively, these results indicate that GOx-CAT-GMPs are highly effective oxygen-regulating materials. These materials can potentially be leveraged to advance gut microbiome research and fecal microbiota transplantation, particularly in low-resource settings.}, }
@article {pmid33553973, year = {2021}, author = {Bajaj, JS and Shamsaddini, A and Fagan, A and Sterling, RK and Gavis, E and Khoruts, A and Fuchs, M and Lee, H and Sikaroodi, M and Gillevet, PM}, title = {Fecal Microbiota Transplant in Cirrhosis Reduces Gut Microbial Antibiotic Resistance Genes: Analysis of Two Trials.}, journal = {Hepatology communications}, volume = {5}, number = {2}, pages = {258-271}, pmid = {33553973}, issn = {2471-254X}, support = {R21 TR002024/TR/NCATS NIH HHS/United States ; R21 TR003095/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Anti-Bacterial Agents/administration &amp; dosage/*adverse effects ; *Drug Resistance, Microbial ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Lactulose/therapeutic use ; Liver Cirrhosis/pathology/*therapy ; Male ; Middle Aged ; Proton Pump Inhibitors/therapeutic use ; Rifaximin/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {Antibiotic resistance leads to poor outcomes in cirrhosis. Fecal microbiota transplant (FMT) is associated with reduction in antibiotic resistance gene (ARG) burden in patients without cirrhosis; however, the impact in cirrhosis is unclear. We aimed to study the effect of capsule and enema FMT on ARG abundance in fecal samples, which were collected during two published FMT trials in patients with cirrhosis on rifaximin, lactulose, and proton pump inhibitors. ARGs were identified using metagenomics and mapped against the Comprehensive Antibiotic Resistance Database. Changes in ARG abundance were studied within/between groups. The capsule FMT trial involved a one-time FMT or placebo capsule administration with stool collection at baseline and week 4 postintervention. Antibiotics+enema FMT included preprocedure antibiotics followed by FMT enema versus standard-of-care (SOC). Stool was collected at baseline, postantibiotics, and day 7/15 postintervention. Both trials included 20 patients each. There was no safety/infection signal linked to FMT. In the capsule trial, beta-lactamase (OXY/LEN) expression decreased post-FMT versus baseline. Compared to placebo, patients who were post-FMT had lower abundance of vancomycin (VanH), beta-lactamase (ACT), and rifamycin ARGs; the latter was associated with cognitive improvement. No changes were seen within patients treated with placebo. In the antibiotics+enema trial for postantibiotics at day 7 versus baseline, there was an increase in vancomycin and beta-lactamase ARGs, which decreased at day 15. However, quinolone resistance increased at day 15 versus baseline. Between SOC and FMT, day 7 had largely lower ARG (CfxA beta-lactamase, VanW, and VanX) that continued at day 15 (cepA beta-lactamase, VanW). No changes were seen within the SOC group. Conclusion: Despite differences in routes of administration and preintervention antibiotics, we found that ARG abundance is largely reduced after FMT compared to pre-FMT baseline and non-FMT groups in decompensated cirrhosis.}, }
@article {pmid33553045, year = {2020}, author = {Mohammadi, SO and Yadegar, A and Kargar, M and Mirjalali, H and Kafilzadeh, F}, title = {The impact of Helicobacter pylori infection on gut microbiota-endocrine system axis; modulation of metabolic hormone levels and energy homeostasis.}, journal = {Journal of diabetes and metabolic disorders}, volume = {19}, number = {2}, pages = {1855-1861}, pmid = {33553045}, issn = {2251-6581}, abstract = {The gut microbiota is a complex ecosystem that is involved in the development and preservation of the immune system, energy homeostasis and nutritional status of the host. The crosstalk between gut microbiota and the host cells modulates host physiology and metabolism through different mechanisms. Helicobacter pylori (H. pylori) is known to reside in the gastric mucosa, induce inflammation, and alter both gastric and intestinal microbiota resulting in a broad spectrum of diseases, in particular metabolic syndrome-related disorders. Infection with H. pylori have been shown to affect production level and physiological regulation of the gut metabolic hormones such as ghrelin and leptin which are involved in food intake, energy expenditure and body mass. In this study, we reviewed and discussed data from the literature and follow-up investigations that links H. pylori infection to alterations of the gut microbiota and metabolic hormone levels, which can exert broad influences on host metabolism, energy homeostasis, behavior, appetite, growth, reproduction and immunity. Also, we discussed the strong potential of fecal microbiota transplantation (FMT) as an innovative and promising investigational treatment option for homeostasis of metabolic hormone levels to overcome H. pylori-associated metabolic syndrome-related disorders.}, }
@article {pmid33549265, year = {2021}, author = {Kwon, J and Stancampiano, FF}, title = {56-Year-Old Man With Profuse Diarrhea.}, journal = {Mayo Clinic proceedings}, volume = {96}, number = {2}, pages = {478-482}, doi = {10.1016/j.mayocp.2020.06.067}, pmid = {33549265}, issn = {1942-5546}, mesh = {Colonoscopy ; Cryptosporidiosis/*diagnosis/drug therapy ; Diagnosis, Differential ; Diarrhea/*etiology ; Feces/chemistry ; Humans ; Hypoalbuminemia/etiology ; Immunocompromised Host ; Kidney Transplantation ; Male ; Middle Aged ; Mycophenolic Acid/adverse effects ; Nitro Compounds/therapeutic use ; Protein-Losing Enteropathies/*complications/diagnosis/diet therapy ; Thiazoles/therapeutic use ; Travel ; alpha 1-Antitrypsin/metabolism ; }, }
@article {pmid33549144, year = {2021}, author = {Strati, F and Pujolassos, M and Burrello, C and Giuffrè, MR and Lattanzi, G and Caprioli, F and Troisi, J and Facciotti, F}, title = {Antibiotic-associated dysbiosis affects the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in experimental colitis models.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {39}, pmid = {33549144}, issn = {2049-2618}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects/pharmacology ; Colitis/*chemically induced/immunology/*microbiology/pathology ; *Disease Models, Animal ; Dysbiosis/chemically induced/*microbiology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/immunology ; Humans ; Male ; Metronidazole/pharmacology ; Mice ; Natural Killer T-Cells/drug effects/immunology ; Streptomycin/adverse effects ; Th1 Cells/drug effects/immunology ; Th17 Cells/drug effects/immunology ; Vancomycin/adverse effects ; }, abstract = {BACKGROUND: The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies.<br><br>RESULTS: Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4[+] T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10.<br><br>CONCLUSIONS: Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites. Video Abstract.}, }
@article {pmid33549047, year = {2021}, author = {Xu, F and Li, N and Wang, C and Xing, H and Chen, D and Wei, Y}, title = {Clinical efficacy of fecal microbiota transplantation for patients with small intestinal bacterial overgrowth: a randomized, placebo-controlled clinic study.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {54}, pmid = {33549047}, issn = {1471-230X}, mesh = {*Bacterial Infections ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Lactulose ; Treatment Outcome ; }, abstract = {BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is characterized by the condition that bacteria overgrowth in the small intestine. Fecal microbiota transplantation (FMT) has been applied as an effective tool for reestablishing the structure of gut microbiota. However, whether FMT could be applied as a routine SIBO treatment has not been investigated.<br><br>METHODS: In this trial, 55 SIBO patients were enrolled. All participants were randomized in two groups, and were given FMT capsule or placebo capsules once a week for 4 consecutive weeks. Measurements including the lactulose hydrogen breath test gastrointestinal symptoms, as well as fecal microbiota diversity were assessed before and after FMT therapy.<br><br>RESULTS: Gastrointestinal symptoms significantly improved in SIBO patients after treatment with FMT compared to participants in placebo group. The gut microbiota diversity of FMT group had a significant increase, while placebo group showed none.<br><br>CONCLUSIONS: This study suggests that applying FMT for patients with SIBO can alleviate gastrointestinal symptoms, indicating that FMT may be a promising and novel therapeutic regimen for SIBO. Trial registry This study was retrospectively registered with the Chinese Clinical Trial registry on 2019.7.10 (ID: ChiCTR1900024409, http://www.chictr.org.cn).}, }
@article {pmid33547298, year = {2021}, author = {Normington, C and Moura, IB and Bryant, JA and Ewin, DJ and Clark, EV and Kettle, MJ and Harris, HC and Spittal, W and Davis, G and Henn, MR and Ford, CB and Wilcox, MH and Buckley, AM}, title = {Biofilms harbour Clostridioides difficile, serving as a reservoir for recurrent infection.}, journal = {NPJ biofilms and microbiomes}, volume = {7}, number = {1}, pages = {16}, pmid = {33547298}, issn = {2055-5008}, mesh = {Aged ; Aged, 80 and over ; Bacteriological Techniques ; Biofilms/drug effects/*growth &amp; development ; Clostridioides difficile/drug effects/*pathogenicity ; Clostridium Infections/drug therapy/*microbiology ; Colon/drug effects/*microbiology ; Fecal Microbiota Transplantation ; Humans ; Middle Aged ; Models, Biological ; Reinfection/drug therapy/microbiology ; Vancomycin/pharmacology ; }, abstract = {C. difficile infection (CDI) is a worldwide healthcare problem with ~30% of cases failing primary therapy, placing a burden on healthcare systems and increasing patient morbidity. We have little understanding of why these therapies fail. Here, we use a clinically validated in vitro gut model to assess the contribution of biofilms towards recurrent disease and to investigate biofilm microbiota-C. difficile interactions. Initial experiments show that C. difficile cells became associated with the colonic biofilm microbiota and are not depleted by vancomycin or faecal microbiota transplant therapies. We observe that transferring biofilm encased C. difficile cells into a C. difficile naïve but CDI susceptible model induces CDI. Members of the biofilm community can impact C. difficile biofilm formation by acting either antagonistically or synergistically. We highlight the importance of biofilms as a reservoir for C. difficile, which can be a cause for recurrent infections.}, }
@article {pmid33547052, year = {2021}, author = {Regen, T and Isaac, S and Amorim, A and Núñez, NG and Hauptmann, J and Shanmugavadivu, A and Klein, M and Sankowski, R and Mufazalov, IA and Yogev, N and Huppert, J and Wanke, F and Witting, M and Grill, A and Gálvez, EJC and Nikolaev, A and Blanfeld, M and Prinz, I and Schmitt-Kopplin, P and Strowig, T and Reinhardt, C and Prinz, M and Bopp, T and Becher, B and Ubeda, C and Waisman, A}, title = {IL-17 controls central nervous system autoimmunity through the intestinal microbiome.}, journal = {Science immunology}, volume = {6}, number = {56}, pages = {}, doi = {10.1126/sciimmunol.aaz6563}, pmid = {33547052}, issn = {2470-9468}, mesh = {Adoptive Transfer ; Animals ; Central Nervous System/immunology/pathology ; Encephalomyelitis, Autoimmune, Experimental/*immunology/microbiology/pathology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Humans ; Interleukin-17/genetics/*metabolism ; Male ; Mice ; Mice, Knockout ; Multiple Sclerosis/*immunology/pathology ; Th17 Cells/immunology/transplantation ; }, abstract = {Interleukin-17A- (IL-17A) and IL-17F-producing CD4[+] T helper cells (TH17 cells) are implicated in the development of chronic inflammatory diseases, such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). TH17 cells also orchestrate leukocyte invasion of the central nervous system (CNS) and subsequent tissue damage. However, the role of IL-17A and IL-17F as effector cytokines is still confused with the encephalitogenic function of the cells that produce these cytokines, namely, TH17 cells, fueling a long-standing debate in the neuroimmunology field. Here, we demonstrated that mice deficient for IL-17A/F lose their susceptibility to EAE, which correlated with an altered composition of their gut microbiota. However, loss of IL-17A/F in TH cells did not diminish their encephalitogenic capacity. Reconstitution of a wild-type-like intestinal microbiota or reintroduction of IL-17A specifically into the gut epithelium of IL-17A/F-deficient mice reestablished their susceptibility to EAE. Thus, our data demonstrated that IL-17A and IL-17F are not encephalitogenic mediators but rather modulators of intestinal homeostasis that indirectly alter CNS-directed autoimmunity.}, }
@article {pmid33546671, year = {2021}, author = {Reisenauer, C and Amend, B and Falch, C and Abele, H and Brucker, SY and Andress, J}, title = {Evaluation and management of obstetric genital fistulas treated at a pelvic floor centre in Germany.}, journal = {BMC women's health}, volume = {21}, number = {1}, pages = {52}, pmid = {33546671}, issn = {1472-6874}, mesh = {Child ; Female ; Germany ; Humans ; *Pelvic Floor ; Pregnancy ; Rectovaginal Fistula/etiology/surgery ; *Vesicovaginal Fistula/etiology/surgery ; }, abstract = {BACKGROUND: Obstetric genital fistulas are an uncommon condition in developed countries. We evaluated their causes and management in women treated at a German pelvic floor centre.<br><br>METHODS: Women who had undergone surgery for obstetric genital fistulas between January 2006 and June 2020 were identified, and their records were reviewed retrospectively.<br><br>RESULTS: Eleven out of 40 women presented with genitourinary fistulas, and 29 suffered from rectovaginal fistulas. In our cohort, genitourinary fistulas were more common in multiparous women (9/11), and rectovaginal fistulas were more common in primiparous women (24/29). The majority of the genitourinary fistulas were at a high anterior position in the vagina, and all rectovaginal fistulas were at a low posterior position. While all genitourinary fistulas were successfully closed, rectovaginal fistula closure was achieved in 88.65% of cases. Women who suffered from rectovaginal fistulas and were at high risk of recurrence or postoperative functional discomfort and desired another child, we recommended fistula repair in the context of a subsequent delivery. For the first time, pregnancy-related changes in the vaginal wall were used to optimize the success rate of fistula closure.<br><br>CONCLUSIONS: In developed countries, birth itself can lead to injury-related genital fistulas. As fistula repair lacks evidence-based guidance, management must be tailored to the underlying pathology and the surgeon's experience. Attention should be directed towards preventive obstetric practice and adequate perinatal and postpartum care. Although vesicovaginal fistulas occur rarely, in case of urinary incontinence after delivery, attention should be paid to the patient, and a vesicovaginal fistula should be ruled out. Trial registration Retrospectively registered, DRKS 00022543, 28.07.2020.}, }
@article {pmid33546192, year = {2021}, author = {Parker, KD and Maurya, AK and Ibrahim, H and Rao, S and Hove, PR and Kumar, D and Kant, R and Raina, B and Agarwal, R and Kuhn, KA and Raina, K and Ryan, EP}, title = {Dietary Rice Bran-Modified Human Gut Microbial Consortia Confers Protection against Colon Carcinogenesis Following Fecal Transfaunation.}, journal = {Biomedicines}, volume = {9}, number = {2}, pages = {}, pmid = {33546192}, issn = {2227-9059}, support = {5R01CA201112/NH/NIH HHS/United States ; }, abstract = {Rice bran, removed from whole grain rice for white rice milling, has demonstrated efficacy for the control and suppression of colitis and colon cancer in multiple animal models. Dietary rice bran intake was shown to modify human stool metabolites as a result of modifications to metabolism by gut microbiota. In this study, human stool microbiota from colorectal cancer (CRC) survivors that consumed rice bran daily was examined by fecal microbiota transplantation (FMT) for protection from azoxymethane and dextran sodium sulfate (AOM/DSS) induced colon carcinogenesis in germ-free mice. Mice transfaunated with rice bran-modified microbiota communities (RMC) harbored fewer neoplastic lesions in the colon and displayed distinct enrichment of Flavonifractor and Oscillibacter associated with colon health, and the depletion of Parabacteroides distasonis correlated with increased tumor burden. Two anti-cancer metabolites, myristoylcarnitine and palmitoylcarnitine were increased in the colon of RMC transplanted mice. Trimethylamine-N-oxide (TMAO) and tartarate that are implicated in CRC development were reduced in murine colon tissue after FMT with rice bran-modified human microbiota. Findings from this study show that rice bran modified gut microbiota from humans confers protection from colon carcinogenesis in mice and suggests integrated dietary-FMT intervention strategies should be tested for colorectal cancer control, treatment, and prevention.}, }
@article {pmid33546191, year = {2021}, author = {Plaza-Díaz, J and Solis-Urra, P and Aragón-Vela, J and Rodríguez-Rodríguez, F and Olivares-Arancibia, J and Álvarez-Mercado, AI}, title = {Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis.}, journal = {Biomedicines}, volume = {9}, number = {2}, pages = {}, pmid = {33546191}, issn = {2227-9059}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).}, }
@article {pmid33545935, year = {2021}, author = {Choi, E and Lee, SJ and Lee, S and Yi, J and Lee, YS and Chang, SY and Jeong, HY and Joo, Y}, title = {Comprehensive, multisystem, mechanical decolonization of Vancomycin-Resistant Enterococcus and Carbapenem-Resistant Enterobacteriacease without the use of antibiotics.}, journal = {Medicine}, volume = {100}, number = {3}, pages = {e23686}, pmid = {33545935}, issn = {1536-5964}, mesh = {Aged ; Bedding and Linens/microbiology ; Carbapenem-Resistant Enterobacteriaceae/*isolation &amp; purification ; Chlorhexidine/administration &amp; dosage ; Clinical Protocols ; Clothing ; Cross Infection/microbiology/*therapy/transmission ; Enema/methods ; Enterobacteriaceae Infections/microbiology/*therapy/transmission ; Environmental Microbiology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Hygiene ; Infection Control/*methods ; Lactobacillus/metabolism ; Male ; Middle Aged ; Prospective Studies ; Quarantine ; Skin/microbiology ; Treatment Outcome ; Vancomycin-Resistant Enterococci/*isolation &amp; purification ; }, abstract = {Among multidrug-resistant organisms (MDROs), Vancomycin-resistant Enterococcus (VRE), and Carbapenem-resistant Enterobacteriaceae (CRE) have become major nosocomial pathogens that are endemic worldwide. If VRE/CRE are present as colonizing organisms but do not act as pathogens, these organisms do not cause symptoms and do not require antibiotic use. However, once gastrointestinal colonization with VRE/CRE occurs, it can persist for long periods and serve as a reservoir for transmission to other patients. Therefore, a breakthrough strategy to control the spread of MDRO colonization is needed. We herein introduce decolonization method, which is a comprehensive, multisystem, consecutive mechanical MDRO decolonization protocol that does not utilize antibiotics. Our protocol included: (1).. Mechanical evacuation using a glycerin enema, (2).. Replacement of the normal gut flora using daily lactobacillus ingestion, (3).. Skin hygiene cleansing using chlorhexidine, and (4).. Environmental cleansing by changing the bed sheets and clothing every day. These steps were repeated consecutively until the patient was released from quarantine. We conducted VRE/CRE tests every week. Because our protocol was a comprehensive and multisystem decolonization protocol, the cooperation of patients and/or caregivers was essential, and family support was important for patient care. Patients were divided into VRE and CRE groups and were subdivided into success and failure groups according to decolonization status. Thirty-two patients with VRE or CRE colonization were enrolled, and our protocol was performed. A total of 20 patients (62.5%) were successfully decolonized after repeated protocols. Univariate analysis revealed that patients with younger age, higher body mass index (BMI), shorter period of MDRO isolation without trial, and higher functional status showed significantly enhanced success rates with our decolonization protocol. This study presents the decolonization effects of a comprehensive, multisystem, mechanical decolonization protocol for VRE and CRE. Most importantly, our decolonization protocol does not use antibiotics and is thus not harmful. These results suggest an active decolonization trial to be performed as early as possible in patients with VRE or CRE colonization. This simple, easy-to-apply protocol can be used as 1 of the basic treatment options for MDROs infection or colonization, regardless of whether it requires antibiotic treatment.}, }
@article {pmid33542131, year = {2021}, author = {Davar, D and Dzutsev, AK and McCulloch, JA and Rodrigues, RR and Chauvin, JM and Morrison, RM and Deblasio, RN and Menna, C and Ding, Q and Pagliano, O and Zidi, B and Zhang, S and Badger, JH and Vetizou, M and Cole, AM and Fernandes, MR and Prescott, S and Costa, RGF and Balaji, AK and Morgun, A and Vujkovic-Cvijin, I and Wang, H and Borhani, AA and Schwartz, MB and Dubner, HM and Ernst, SJ and Rose, A and Najjar, YG and Belkaid, Y and Kirkwood, JM and Trinchieri, G and Zarour, HM}, title = {Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6529}, pages = {595-602}, pmid = {33542131}, issn = {1095-9203}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA222203/CA/NCI NIH HHS/United States ; R01 CA228181/CA/NCI NIH HHS/United States ; }, mesh = {Antibodies, Monoclonal, Humanized/*therapeutic use ; Antineoplastic Agents, Immunological/*therapeutic use ; CD8-Positive T-Lymphocytes/immunology ; *Drug Resistance, Neoplasm ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Interleukin-8/immunology ; Lymphocyte Activation ; Lymphocytes, Tumor-Infiltrating/immunology ; Melanoma/*therapy ; Myeloid Cells/immunology ; Programmed Cell Death 1 Receptor/*antagonists &amp; inhibitors ; Skin Neoplasms/*therapy ; Tumor Microenvironment/immunology ; }, abstract = {Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8[+] T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma.}, }
@article {pmid33542126, year = {2021}, author = {Woelk, CH and Snyder, A}, title = {Modulating gut microbiota to treat cancer.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6529}, pages = {573-574}, doi = {10.1126/science.abg2904}, pmid = {33542126}, issn = {1095-9203}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy ; *Melanoma ; *Microbiota ; }, }
@article {pmid33540919, year = {2021}, author = {Adamkova, P and Hradicka, P and Gancarcikova, S and Kassayova, M and Ambro, L and Bertkova, I and Maronek, M and Farkasova Iannaccone, S and Demeckova, V}, title = {Single Donor FMT Reverses Microbial/Immune Dysbiosis and Induces Clinical Remission in a Rat Model of Acute Colitis.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {33540919}, issn = {2076-0817}, support = {APVV-16-0176//Agent&#xfa;ra na Podporu V&#xfd;skumu a V&#xfd;voja/ ; VVGS-2019-1073, VVGS-2019-1226//Vn&#xfa;torn&#xfd; vedeck&#xfd; grantov&#xfd; syst&#xe9;m UPJ&#x160; v Ko&#x161;iciach/ ; }, abstract = {Deviation in the gut microbial composition is involved in various pathologies, including inflammatory bowel disease (IBD). Faecal microbiota transplant (FMT) can act as a promising approach to treat IBD by which changes in microbiome can be reversed and homeostasis restored. Therefore, the aim of this study was to investigate the effect of FMT on the remission of acute inflammatory response using dextran sulfate sodium (DSS)-induced rat colitis model. Faecal microbial communities were analysed using the 16S rRNA approach, and clinical manifestations together with histological/haematological/biochemical/immunological analyses were assessed. Our study demonstrated significant shifts in the dominant species of microbiota under inflammatory conditions induced by DSS and evident restoration effect of FMT treatment on microbial composition. These faecal microbial alterations in FMT-treated rats led to a relative restoration of colon length, and a significant decrease in both epithelium damage and disease severity, which was reflected in lower serum pro-inflammatory cytokine levels. Haematological/biochemical parameters in DSS-treated animals showed signs of anaemia with a significant reduction in red blood cell count together with increasing levels of total bilirubin, creatinine and phosphorus suggesting potential protective effect of FMT. These results support FMT as a valuable therapeutic strategy to control inflammation during acute colitis.}, }
@article {pmid33538872, year = {2021}, author = {Boccasanta, P and Venturi, M and Agradi, S and Calabrò, G and Bordoni, L and Missaglia, C and Favetta, U and Vergani, C}, title = {Is it possible to reduce recurrences after Altemeier's procedure for complete rectal prolapse? Twenty-year experience in 130 consecutive patients.}, journal = {Langenbeck's archives of surgery}, volume = {406}, number = {5}, pages = {1591-1598}, pmid = {33538872}, issn = {1435-2451}, mesh = {Humans ; Quality of Life ; *Rectal Prolapse/surgery ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {PURPOSE: In the attempt to understand the reasons for and to find a solution to the high recurrence rate after perineal surgery for complete rectal prolapse, we retrospectively analysed the long-term results of Altemeier's procedure alone, or associated with Trans-Obturator Colonic Suspension (TOCS) in a large series of patients with a median interval of 84 months (range 6-258).<br><br>METHODS: Medical records of 110 patients undergoing Altemeier with levatorplasty (group 1) and 20 patients submitted to the same procedure associated with TOCS (group 2) for newly diagnosed complete rectal prolapse were reviewed. All patients had been recruited after preoperative clinical examination, SF-36 quality of life, continence score and colonoscopy.<br><br>RESULTS: Mortality was nil. The overall complication and the recurrence rates were 12.3%, and 15.0% (P= 0.769) and 24.6% and 5.0% (P=0.067) in group 1 and 2, respectively. Twelve patients of group 1 with a recurrence were submitted to a redo-Altemeier, 8 to a redo-Altemeier associated with TOCS, and 6 associated with an anterior coloplasty with a mesh. The only patient of group 2 with a recurrence was submitted to a Hartmann's operation. Preoperative vs postoperative mean (SD) continence score was 15.8 (3.1) and 15.6 (3.3) versus 4.1 (1.8) and 3.9 (1.9) in group 1 and 2, respectively (P < 0.001). All parameters of SF-36 improved after surgery (P<0.01) and no differences between the 2 groups were found CONCLUSIONS: Long-term results confirmed the safety and effectiveness of Altemeier's procedure for the treatment of complete rectal prolapse, with the limit of a non-negligible incidence of anastomotic complications and recurrences. The combination of Altemeier with TOCS showed a positive trend to a reduction of the recurrence rate, not worsening morbidity and outcomes.}, }
@article {pmid33537709, year = {2022}, author = {Kim, M and Huda, MN and Bennett, BJ}, title = {Sequence meets function-microbiota and cardiovascular disease.}, journal = {Cardiovascular research}, volume = {118}, number = {2}, pages = {399-412}, pmid = {33537709}, issn = {1755-3245}, support = {R01 HL128572/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/genetics/growth &amp; development/*metabolism ; Cardiovascular Diseases/diet therapy/metabolism/*microbiology/physiopathology ; Cardiovascular System/metabolism/physiopathology ; Diet, Healthy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Heart Disease Risk Factors ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology ; *Metabolome ; Metabolomics ; Mouth/microbiology ; Prognosis ; Ribotyping ; Risk Assessment ; }, abstract = {The discovery that gut-microbiota plays a profound role in human health has opened a new avenue of basic and clinical research. Application of ecological approaches where the bacterial 16S rRNA gene is queried has provided a number of candidate bacteria associated with coronary artery disease and hypertension. We examine the associations between gut microbiota and a variety of cardiovascular disease (CVD) including atherosclerosis, coronary artery disease, and blood pressure. These approaches are associative in nature and there is now increasing interest in identifying the mechanisms underlying these associations. We discuss three potential mechanisms including: gut permeability and endotoxemia, increased immune system activation, and microbial derived metabolites. In addition to discussing these potential mechanisms we highlight current studies manipulating the gut microbiota or microbial metabolites to move beyond sequence-based association studies. The goal of these mechanistic studies is to determine the mode of action by which the gut microbiota may affect disease susceptibility and severity. Importantly, the gut microbiota appears to have a significant effect on host metabolism and CVD by producing metabolites entering the host circulatory system such as short-chain fatty acids and trimethylamine N-Oxide. Therefore, the intersection of metabolomics and microbiota research may yield novel targets to reduce disease susceptibility. Finally, we discuss approaches to demonstrate causality such as specific diet changes, inhibition of microbial pathways, and fecal microbiota transplant.}, }
@article {pmid33537028, year = {2020}, author = {Gill, T and Rosenbaum, JT}, title = {Putative Pathobionts in HLA-B27-Associated Spondyloarthropathy.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {586494}, pmid = {33537028}, issn = {1664-3224}, support = {R01 EY029266/EY/NEI NIH HHS/United States ; P30 EY010572/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Gastrointestinal Microbiome/*immunology ; HLA-B27 Antigen/*genetics ; Humans ; Spondylarthropathies/*genetics/*immunology/*microbiology ; }, abstract = {Spondyloarthritis (SpA) is a group of immune mediated inflammatory diseases with a strong association to the major histocompatibility (MHC) class I molecule, HLA-B27. Although the association between HLA-B27 and AS has been known for almost 50 years, the mechanisms underlying disease pathogenesis are elusive. Over the years, three hypotheses have been proposed to explain HLA-B27 and disease association: 1) HLA B27 presents arthritogenic peptides and thus creates a pathological immune response; 2) HLA-B27 misfolding causes endoplasmic reticulum (ER) stress which activates the unfolded protein response (UPR); 3) HLA-B27 dimerizes on the cell surface and acts as a target for natural killer (NK) cells. None of these hypotheses explains SpA pathogenesis completely. Evidence supports the hypothesis that HLA-B27-related diseases have a microbial pathogenesis. In animal models of various SpAs, a germ-free environment abrogates disease development and colonizing these animals with gut commensal microbes can restore disease manifestations. The depth of microbial influence on SpA development has been realized due to our ability to characterize microbial communities in the gut using next-generation sequencing approaches. In this review, we will discuss various putative pathobionts in the pathogenesis of HLA-B27-associated diseases. We pursue whether a single pathobiont or a disruption of microbial community and function is associated with HLA-B27-related diseases. Furthermore, rather than a specific pathobiont, metabolic functions of various disease-associated microbes might be key. While the use of germ-free models of SpA have facilitated understanding the role of microbes in disease development, future studies with animal models that mimic diverse microbial communities instead of mono-colonization are indispensable. We discuss the causal mechanisms underlying disease pathogenesis including the role of these pathobionts on mucin degradation, mucosal adherence, and gut epithelial barrier disruption and inflammation. Finally, we review the various uses of microbes as therapeutic modalities including pre/probiotics, diet, microbial metabolites and fecal microbiota transplant. Unravelling these complex host-microbe interactions will lead to the development of new targets/therapies for alleviation of SpA and other HLA-B27 associated diseases.}, }
@article {pmid33536363, year = {2021}, author = {Seo, HS and Chin, HS and Kim, YH and Moon, HS and Kim, K and Nguyen, LP and Yong, D}, title = {Laboratory Aspects of Donor Screening for Fecal Microbiota Transplantation at a Korean Fecal Microbiota Bank.}, journal = {Annals of laboratory medicine}, volume = {41}, number = {4}, pages = {424-428}, pmid = {33536363}, issn = {2234-3814}, mesh = {Clostridium Infections/diagnosis/therapy ; Donor Selection ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Laboratories ; *Microbiota ; Republic of Korea ; }, abstract = {Fecal microbiota transplantation (FMT) is a widely accepted alternative therapy for Clostridioides difficile infection and other gastrointestinal disorders. Thorough donor screening is required as a safety control measure to minimize transmission of infectious agents in FMT. We report the donor screening process and outcomes at a fecal microbiota bank in Korea. From August 2017 to June 2020, the qualification of 62 individuals as FMT donors was evaluated using clinical assessment and laboratory tests. Forty-six (74%) candidates were excluded after clinical assessment; high body mass index (>25) was the most common reason for exclusion, followed by atopy, asthma, and allergy history. Four of the remaining 16 (25%) candidates failed to meet laboratory test criteria, resulting in a 19% qualification rate. FMT donor re-qualification was conducted monthly as an additional safety control measure, and only three (5%) candidates were eligible for repeated donation. As high prevalence of multidrug-resistant organisms (55%) and Helicobacter pylori (44%) were detected in qualified donors during the screening, a urea breath test was added to the existing protocol. The present results emphasize the importance of implementing a donor re-qualification system to minimize risk factors not identified during initial donor screening.}, }
@article {pmid33535876, year = {2021}, author = {Seyfried, F and Phetcharaburanin, J and Glymenaki, M and Nordbeck, A and Hankir, M and Nicholson, JK and Holmes, E and Marchesi, JR and Li, JV}, title = {Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-20}, pmid = {33535876}, issn = {1949-0984}, support = {MR/P002536/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Bile Acids and Salts/analysis ; Blood Glucose ; Body Weight ; *Caloric Restriction ; Eating ; Fatty Acids, Volatile/analysis ; Feces/chemistry/microbiology ; *Gastric Bypass ; Male ; Obesity/metabolism/microbiology/surgery ; Rats ; Rats, Zucker ; Weight Loss/*physiology ; gamma-Aminobutyric Acid/analysis ; }, abstract = {Mechanisms of Roux-en-Y gastric bypass (RYGB) surgery are not fully understood. This study aimed to investigate weight loss-independent bacterial and metabolic changes, as well as the absorption of bacterial metabolites and bile acids through the hepatic portal system following RYGB surgery. Three groups of obese Zucker (fa/fa) rats were included: RYGB (n = 11), sham surgery and body weight matched with RYGB (Sham-BWM, n = 5), and sham surgery fed ad libitum (Sham-obese, n = 5). Urine and feces were collected at multiple time points, with portal vein and peripheral blood obtained at the end of the study. Metabolic phenotyping approaches and 16S rRNA gene sequencing were used to determine the biochemical and bacterial composition of the samples, respectively. RYGB surgery-induced distinct metabolic and bacterial disturbances, which were independent of weight loss through caloric restriction. RYGB resulted in lower absorption of phenylalanine and choline, and higher urinary concentrations of host-bacterial co-metabolites (e.g., phenylacetylglycine, indoxyl sulfate), together with higher fecal trimethylamine, suggesting enhanced bacterial aromatic amino acid and choline metabolism. Short chain fatty acids (SCFAs) were lower in feces and portal vein blood from RYGB group compared to Sham-BWM, accompanied with lower abundances of Lactobacillaceae, and Ruminococcaceae known to contain SCFA producers, indicating reduced bacterial fiber fermentation. Fecal γ-amino butyric acid (GABA) was found in higher concentrations in RYGB than that in Sham groups and could play a role in the metabolic benefits associated with RYGB surgery. While no significant difference in urinary BA excretion, RYGB lowered both portal vein and circulating BA compared to Sham groups. These findings provide a valuable resource for how dynamic, multi-systems changes impact on overall metabolic health, and may provide potential therapeutic targets for developing downstream non-surgical treatment for metabolic disease.}, }
@article {pmid33535557, year = {2021}, author = {Parisi, A and Porzio, G and Pulcini, F and Cannita, K and Ficorella, C and Mattei, V and Delle Monache, S}, title = {What Is Known about Theragnostic Strategies in Colorectal Cancer.}, journal = {Biomedicines}, volume = {9}, number = {2}, pages = {}, pmid = {33535557}, issn = {2227-9059}, abstract = {Despite the paradigmatic shift occurred in recent years for defined molecular subtypes in the metastatic setting treatment, colorectal cancer (CRC) still remains an incurable disease in most of the cases. Therefore, there is an urgent need for new tools and biomarkers for both early tumor diagnosis and to improve personalized treatment. Thus, liquid biopsy has emerged as a minimally invasive tool that is capable of detecting genomic alterations from primary or metastatic tumors, allowing the prognostic stratification of patients, the detection of the minimal residual disease after surgical or systemic treatments, the monitoring of therapeutic response, and the development of resistance, establishing an opportunity for early intervention before imaging detection or worsening of clinical symptoms. On the other hand, preclinical and clinical evidence demonstrated the role of gut microbiota dysbiosis in promoting inflammatory responses and cancer initiation. Altered gut microbiota is associated with resistance to chemo drugs and immune checkpoint inhibitors, whereas the use of microbe-targeted therapies including antibiotics, pre-probiotics, and fecal microbiota transplantation can restore response to anticancer drugs, promote immune response, and therefore support current treatment strategies in CRC. In this review, we aim to summarize preclinical and clinical evidence for the utilization of liquid biopsy and gut microbiota in CRC.}, }
@article {pmid33534361, year = {2021}, author = {Rajindrajith, S and Devanarayana, NM and Thapar, N and Benninga, MA}, title = {Functional Fecal Incontinence in Children: Epidemiology, Pathophysiology, Evaluation, and Management.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {72}, number = {6}, pages = {794-801}, pmid = {33534361}, issn = {1536-4801}, mesh = {Child ; Colon ; Constipation/diagnosis/epidemiology/etiology ; *Fecal Incontinence/diagnosis/epidemiology/etiology ; Humans ; Manometry ; Quality of Life ; }, abstract = {Functional fecal incontinence (FI) is a worldwide problem in children and comprises constipation-associated FI and nonretentive FI. Irrespective of pathophysiology, both disorders impact negatively on the psychological well-being and quality of life of affected children. A thorough clinical history and physical examination using the Rome IV criteria are usually sufficient to diagnose these conditions in most children. Evolving investigations such as high-resolution anorectal and colonic manometry have shed new light on the pathophysiology of functional FI. Although conventional interventions such as toilet training and laxatives successfully treat most children with constipation-associated FI, children with nonretentive FI need more psychologically based therapeutic options. Intrasphincteric injection of botulinum toxin, transanal irrigation and, in select cases, surgical interventions have been used in more resistant children with constipation-associated FI.}, }
@article {pmid33534360, year = {2021}, author = {Ruan, W and Kellermayer, R}, title = {Alternative Diagnoses in Pediatric Fecal Microbiota Transplant Referral Patients.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {72}, number = {5}, pages = {693-696}, pmid = {33534360}, issn = {1536-4801}, mesh = {Adult ; Child ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Referral and Consultation ; Retrospective Studies ; Treatment Outcome ; }, abstract = {The incidence of Clostridioides difficile infection (CDI) has been increasing in the United States. About 10-20% recur after initial treatment, with increasing recurrence following subsequent treatment courses. This sequence can lead to recurrent CDI (rCDI), refractory to conventional therapeutics resulting in the most common indication for fecal microbiota transplantation (FMT). FMT is the most effective microbial therapeutic to date and can cure rCDI in 80-90% of cases. There is growing concern, however, for pathogen transmission through FMT, underscoring the importance of careful recipient selection. In adults referred for FMT with a tentative diagnosis of rCDI, alternative diagnoses were recognized in 25% of patients, but such observation in children is lacking. In this single-center retrospective study, alternative diagnoses (eg, constipation/overflow diarrhea, inflammatory bowel disease) were found in 13 (22.4%) of 58 children who were referred for FMT evaluation for rCDI. Of the patients who were diagnosed with rCDI, 16 (27.6%) did not require FMT.}, }
@article {pmid33533699, year = {2020}, author = {Durham, SH and Le, P and Cassano, AT}, title = {Navigating changes in Clostridioides difficile prevention and treatment.}, journal = {Journal of managed care &amp; specialty pharmacy}, volume = {26}, number = {12-a Suppl}, pages = {S3-S23}, pmid = {33533699}, issn = {2376-1032}, mesh = {Anti-Bacterial Agents/economics/*therapeutic use ; Bacterial Vaccines/economics/*therapeutic use ; Clinical Decision-Making ; Clinical Trials as Topic ; Clostridioides difficile/drug effects/immunology/pathogenicity ; Clostridium Infections/economics/epidemiology/immunology/*therapy ; Cost-Benefit Analysis ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/immunology ; Humans ; Incidence ; Practice Guidelines as Topic ; Probiotics/*administration &amp; dosage/economics ; Recurrence ; Societies, Medical/standards ; Treatment Outcome ; United States/epidemiology ; }, abstract = {Clostridioides difficile (C. difficile, previously known as Clostridium difficile) infections are a major health care concern. The Centers for Disease Control and Prevention (CDC) estimates that C. difficile causes almost half a million illnesses in the United States yearly, and approximately 1 in 5 patients with a C. difficile infection (CDI) will experience 1 or more recurrent infections. The incidence of infection has risen dramatically in recent years, and infection severity has increased due to the emergence of hypervirulent strains. There have been noteworthy advances in the development of CDI prevention and treatment, including a growth in the understanding of the role a patient's gut microbiome plays. The 2017 Infectious Diseases Society of America (IDSA) guidelines made a significant change in treatment recommendations for first time CDI episodes by recommending the use of oral vancomycin or fidaxomicin in place of metronidazole as a first-line treatment. The guidelines also included detailed recommendations on the use of fecal microbiota transplant (FMT) in those patients who experience 3 or more recurrent CDI episodes. A number of novel therapies for the treatment of CDI are in various stages of development. Treatments currently in phase 3 trials include the antibiotic ridinilazole, the microbiome products SER-109 and RBX2660, and a vaccine. All of these agents have shown promise in phase 1 and 2 trials. Additionally, several other antibiotic and microbiome candidates are currently in phase 1 or phase 2 trials. A qualitative review and evaluation of the literature on the cost-effectiveness of treatments for CDI in the U.S. setting was conducted, and the summary provided herein. Due to the higher cost of newer agents, cost-effectiveness evaluations will continue to be critical in clinical decision making for CDI. This paper reviews the updated CDI guidelines for prevention and treatment, the role of the microbiome in new and recurrent infections, pipeline medications, and comparative effectiveness research (CER) data on these treatments. DISCLOSURES: Durham and Le have nothing to disclose. Cassano reports consulting fees from Baxter Healthcare. Peer reviewers Drs. Ami Gopalan and Mark Rubin and Ms. Kathleen Jarvis have nothing to disclose. Planners Dr. Christine L. Cooper and Ms. Susan Yarbrough have nothing to disclose.}, }
@article {pmid33532747, year = {2020}, author = {Shin, W and Ambrosini, YM and Shin, YC and Wu, A and Min, S and Koh, D and Park, S and Kim, S and Koh, H and Kim, HJ}, title = {Robust Formation of an Epithelial Layer of Human Intestinal Organoids in a Polydimethylsiloxane-Based Gut-on-a-Chip Microdevice.}, journal = {Frontiers in medical technology}, volume = {2}, number = {}, pages = {}, pmid = {33532747}, issn = {2673-3129}, support = {F99 CA245801/CA/NCI NIH HHS/United States ; K00 CA245801/CA/NCI NIH HHS/United States ; R21 CA236690/CA/NCI NIH HHS/United States ; }, abstract = {Polydimethylsiloxane (PDMS) is a silicone polymer that has been predominantly used in a human organ-on-a-chip microphysiological system. The hydrophobic surface of a microfluidic channel made of PDMS often results in poor adhesion of the extracellular matrix (ECM) as well as cell attachment. The surface modification by plasma or UV/ozone treatment in a PDMS-based device produces a hydrophilic surface that allows robust ECM coating and the reproducible attachment of human intestinal immortalized cell lines. However, these surface-activating methods have not been successful in forming a monolayer of the biopsy-derived primary organoid epithelium. Several existing protocols to grow human intestinal organoid cells in a PDMS microchannel are not always reproducibly operative due to the limited information. Here, we report an optimized methodology that enables robust and reproducible attachment of the intestinal organoid epithelium in a PDMS-based gut-on-a-chip. Among several reported protocols, we optimized a method by performing polyethyleneimine-based surface functionalization followed by the glutaraldehyde cross linking to activate the PDMS surface. Moreover, we discovered that the post-functionalization step contributes to provide uniform ECM deposition that allows to produce a robust attachment of the dissociated intestinal organoid epithelium in a PDMS-based microdevice. We envision that our optimized protocol may disseminate an enabling methodology to advance the integration of human organotypic cultures in a human organ-on-a-chip for patient-specific disease modeling.}, }
@article {pmid33532501, year = {2021}, author = {Diao, H and Xiao, Y and Yan, HL and Yu, B and He, J and Zheng, P and Yu, J and Mao, XB and Chen, DW}, title = {Effects of Early Transplantation of the Faecal Microbiota from Tibetan Pigs on the Gut Development of DSS-Challenged Piglets.}, journal = {BioMed research international}, volume = {2021}, number = {}, pages = {9823969}, pmid = {33532501}, issn = {2314-6141}, mesh = {Animals ; Animals, Suckling/growth &amp; development/physiology ; Dextran Sulfate ; Escherichia coli/genetics ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics/physiology ; *Intestinal Mucosa/growth &amp; development/physiology ; Lactobacillus/genetics ; Swine ; }, abstract = {The present study was conducted to investigate the effects of early transplantation of the faecal microbiota from Tibetan pigs on the gut development of dextran sulphate sodium- (DSS-) challenged piglets. In total, 24 3-day-old DLY piglets were divided into four groups (n = 6 per group); a 2 × 2 factorial arrangement was used, which included faecal microbiota transplantation (FMT) (from Tibetan pigs) and DSS challenge. The whole trial lasted for 55 days. DSS infusion increased the intestinal density, serum diamine oxidase (DAO) activity, and colonic Escherichia coli count (P < 0.05), and decreased the Lactobacillus spp. count and mRNA abundances of epidermal growth factor (EGF), glucagon-like peptide-2 (GLP-2), insulin-like growth factor 1 (IGF-1), occludin, mucin 2 (MUC2), regeneration protein IIIγ (RegIIIγ), and interleukin-10 (IL-10) in the colon (P < 0.05). FMT increased the Lactobacillus spp. count and mRNA abundances of GLP-2, RegIIIγ, and IL-10 in the colon (P < 0.05), and decreased the intestinal density, serum DAO activity, and colonic E. coli number (P < 0.05). In addition, in DSS-challenged piglets, FMT decreased the disease activity index (P < 0.05) and attenuated the effect of DSS challenge on the intestinal density, serum DAO activity, and colonic E. coli number (P < 0.05). These data indicated that the faecal microbiota from Tibetan pigs could attenuate the negative effect of DSS challenge on the gut development of piglets.}, }
@article {pmid33531483, year = {2021}, author = {Littmann, ER and Lee, JJ and Denny, JE and Alam, Z and Maslanka, JR and Zarin, I and Matsuda, R and Carter, RA and Susac, B and Saffern, MS and Fett, B and Mattei, LM and Bittinger, K and Abt, MC}, title = {Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {755}, pmid = {33531483}, issn = {2041-1723}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R00 AI125786/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/immunology/metabolism ; Feces/microbiology ; Forkhead Transcription Factors/metabolism ; Homeodomain Proteins/metabolism ; Inflammation/immunology/metabolism ; Mice ; T-Lymphocytes, Regulatory/immunology/metabolism ; }, abstract = {Fecal microbiota transplantation (FMT) is a successful therapeutic strategy for treating recurrent Clostridioides difficile infection. Despite remarkable efficacy, implementation of FMT therapy is limited and the mechanism of action remains poorly understood. Here, we demonstrate a critical role for the immune system in supporting FMT using a murine C. difficile infection system. Following FMT, Rag1 heterozygote mice resolve C. difficile while littermate Rag1[-/-] mice fail to clear the infection. Targeted ablation of adaptive immune cell subsets reveal a necessary role for CD4[+] Foxp3[+] T-regulatory cells, but not B cells or CD8[+] T cells, in FMT-mediated resolution of C. difficile infection. FMT non-responsive mice exhibit exacerbated inflammation, impaired engraftment of the FMT bacterial community and failed restoration of commensal bacteria-derived secondary bile acid metabolites in the large intestine. These data demonstrate that the host's inflammatory immune status can limit the efficacy of microbiota-based therapeutics to treat C. difficile infection.}, }
@article {pmid33531405, year = {2021}, author = {Haifer, C and Paramsothy, S and Borody, TJ and Clancy, A and Leong, RW and Kaakoush, NO}, title = {Long-Term Bacterial and Fungal Dynamics following Oral Lyophilized Fecal Microbiota Transplantation in Clostridioides difficile Infection.}, journal = {mSystems}, volume = {6}, number = {1}, pages = {}, pmid = {33531405}, issn = {2379-5077}, abstract = {Oral lyophilized fecal microbiota transplantation (FMT) is effective in recurrent Clostridioides difficile infection (CDI); however, limited data exist on its efficacy in primary CDI and long-term microbial engraftment. Patients with primary or recurrent CDI were prospectively enrolled to receive oral FMT. Changes in the bacterial and fungal communities were characterized prior to and up to 6 months following treatment. A total of 37 patients with CDI (15 primary, 22 recurrent) were treated with 6 capsules each containing 0.35-g lyophilized stool extract. A total of 33 patients (89%) had sustained CDI cure, of whom 3 required a second course. There were no safety signals identified. FMT significantly increased bacterial diversity and shifted composition toward donor profiles in responders but not in nonresponders, with robust donor contribution observed to 6 months following FMT (P < 0.001). Responders showed consistent decreases in Enterobacteriaceae and increases in Faecalibacterium sp. to levels seen in donors. Mycobiome profiling revealed an association with FMT failure and increases in one Penicillium taxon, as well as coexclusion relationships between Candida sp. and bacterial taxa enriched in both donors and responders. Primary CDI was associated with more robust changes in the bacterial community than those with recurrent disease. Oral FMT leads to durable microbial engraftment in patients with primary and recurrent CDI, with several microbial taxa being associated with therapy outcome. Novel coexclusion relationships between bacterial and fungal species support the clinical relevance of transkingdom dynamics.IMPORTANCE Clostridioides difficile infection (CDI) is a substantial health concern worldwide, complicated by patterns of increasing antibiotic resistance that may impact primary treatment. Orally administered fecal microbiota transplantation (FMT) is efficacious in the management of recurrent CDI, with specific bacterial species known to influence clinical outcomes. To date, little is known about the efficacy of FMT in primary CDI and the impact of the mycobiome on therapeutic outcomes. We performed matched bacterial and fungal sequencing on longitudinal samples from a cohort of patients treated with oral FMT for primary and recurrent CDI. We validated many bacterial signatures following oral therapy, confirmed engraftment of donor microbiome out to 6 months following therapy, and demonstrated coexclusion relationships between Candida albicans and two bacterial species in the gut microbiota, which has potential significance beyond CDI, including in the control of gut colonization by this fungal species.}, }
@article {pmid33529409, year = {2021}, author = {Subba, R and Sandhir, R and Singh, SP and Mallick, BN and Mondal, AC}, title = {Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control.}, journal = {The European journal of neuroscience}, volume = {53}, number = {8}, pages = {2870-2900}, doi = {10.1111/ejn.15136}, pmid = {33529409}, issn = {1460-9568}, mesh = {Depression/therapy ; *Diabetes Mellitus, Type 2/therapy ; Exercise ; Fecal Microbiota Transplantation ; Humans ; Hypothalamo-Hypophyseal System ; *Microbiota ; Pituitary-Adrenal System ; Psychotherapy ; }, abstract = {Diabetes increases the likelihood of developing depression and vice versa. Research on this bidirectional association has somewhat managed to delineate the interplay among implicated physiological processes. Still, further exploration is required in this context. This review addresses the comorbidity by investigating suspected common pathophysiological mechanisms. One such factor is psychological stress which disturbs the hypothalamic-pituitary-adrenal axis causing hormonal imbalance. This includes elevated cortisol levels, a common biomarker of both depression and diabetes. Disrupted insulin signaling drives the hampered neurotransmission of serotonin, dopamine, and norepinephrine. Also, adipokine hormones such as adiponectin, leptin, and resistin and the orexigenic hormone, ghrelin, are involved in both depression and T2DM. This disarray further interferes with physiological processes encompassing sleep, the gut-brain axis, metabolism, and mood stability. Behavioral coping mechanisms, such as unhealthy eating, mediate disturbed glucose homeostasis, and neuroinflammation. This is intricately linked to oxidative stress, redox imbalance, and mitochondrial dysfunction. However, interventions such as psychotherapy, physical exercise, fecal microbiota transplantation, and insulin-sensitizing agents can help to manage the distressing condition. The possibility of glucagon-like peptide 1 possessing a therapeutic role has also been discussed. Nonetheless, there stands an urgent need for unraveling new correlating targets and biological markers for efficient treatment.}, }
@article {pmid33528685, year = {2021}, author = {Sahni, S and Kassam, H and Yaghooti, N and Birg, A and McCarthy, DM}, title = {Cure My Virus: Hematemesis and Melena in a Transplant Recipient.}, journal = {Digestive diseases and sciences}, volume = {66}, number = {3}, pages = {728-732}, pmid = {33528685}, issn = {1573-2568}, mesh = {Colitis/*virology ; *Cytomegalovirus ; Cytomegalovirus Infections/*complications/virology ; Gastrointestinal Hemorrhage/virology ; Heart Transplantation ; Hematemesis/*virology ; Humans ; Immunosuppression Therapy/adverse effects ; Male ; Medical Illustration ; Melena/*virology ; Middle Aged ; Postoperative Complications/virology ; }, }
@article {pmid33523449, year = {2021}, author = {Liu, Y and Tran, DQ and Lindsey, JW and Rhoads, JM}, title = {The Association of Gut Microbiota and Treg Dysfunction in Autoimmune Diseases.}, journal = {Advances in experimental medicine and biology}, volume = {1278}, number = {}, pages = {191-203}, pmid = {33523449}, issn = {0065-2598}, support = {R01 AT007083/AT/NCCIH NIH HHS/United States ; R03 AI117442/AI/NIAID NIH HHS/United States ; R03 AI153725/AI/NIAID NIH HHS/United States ; }, mesh = {*Autoimmune Diseases/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases ; T-Lymphocytes, Regulatory ; }, abstract = {Autoimmune conditions affect 23 million Americans or 7% of the US population. There are more than 100 autoimmune disorders, affecting every major organ system in humans. This chapter aims to further explain Treg dysfunction autoimmune disorders, including monogenic primary immune deficiency such as immune dysregulation polyendocrinopathy, enteropathy, X-linked inheritance (IPEX) syndrome, and polygenic autoimmune diseases with Treg dysfunction such as multiple sclerosis (MS), inflammatory bowel disease (IBD), and food allergy. These conditions are associated with an abnormal small intestinal and colonic microbiome. Some disorders clearly improve with therapies aimed at microbial modification, including probiotics and fecal microbiota transplantation (FMT). Approaches to prevent and treat these disorders will need to focus on the acquisition and maintenance of a healthy colonic microbiota, in addition to more focused approaches at immune suppression during acute disease exacerbations.}, }
@article {pmid33521100, year = {2021}, author = {Zheng, L and Wen, XL}, title = {Gut microbiota and inflammatory bowel disease: The current status and perspectives.}, journal = {World journal of clinical cases}, volume = {9}, number = {2}, pages = {321-333}, pmid = {33521100}, issn = {2307-8960}, abstract = {Inflammatory bowel disease (IBD) is a chronic immune-mediated disease that affects the gastrointestinal tract. It is argued that environment, microbiome, and immune-mediated factors interact in a genetically susceptible host to trigger IBD. Recently, there has been increased interest in the development, progression, and treatment of IBD because of our understanding of the microbiome. Researchers have proved that some factors can alter the microbiome and the pathogenesis of IBD. As a result, there has been increasing interest in the application of probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and gene manipulation in treating IBD because of the possible curative effect of microbiome-modulating interventions. In this review, we summarize the findings from human and animal studies and discuss the effect of the gut microbiome in treating patients with IBD.}, }
@article {pmid33517890, year = {2021}, author = {Hou, YF and Shan, C and Zhuang, SY and Zhuang, QQ and Ghosh, A and Zhu, KC and Kong, XK and Wang, SM and Gong, YL and Yang, YY and Tao, B and Sun, LH and Zhao, HY and Guo, XZ and Wang, WQ and Ning, G and Gu, YY and Li, ST and Liu, JM}, title = {Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson's disease.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {34}, pmid = {33517890}, issn = {2049-2618}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Disease Models, Animal ; Disease Progression ; Dopaminergic Neurons/drug effects ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Infusions, Parenteral ; Male ; Mice ; Neuroprotective Agents/administration &amp; dosage/*pharmacology ; Osteocalcin/administration &amp; dosage/*pharmacology ; Oxidopamine ; Parkinson Disease/*drug therapy/*metabolism/microbiology/physiopathology ; Propionates/*metabolism ; Receptors, G-Protein-Coupled/agonists/metabolism ; }, abstract = {BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota.<br><br>RESULTS: The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice.<br><br>CONCLUSIONS: Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. Video abstract.}, }
@article {pmid33514598, year = {2021}, author = {Arnoriaga-Rodríguez, M and Mayneris-Perxachs, J and Contreras-Rodríguez, O and Burokas, A and Ortega-Sanchez, JA and Blasco, G and Coll, C and Biarnés, C and Castells-Nobau, A and Puig, J and Garre-Olmo, J and Ramos, R and Pedraza, S and Brugada, R and Vilanova, JC and Serena, J and Barretina, J and Gich, J and Pérez-Brocal, V and Moya, A and Fernández-Real, X and Ramio-Torrentà, L and Pamplona, R and Sol, J and Jové, M and Ricart, W and Portero-Otin, M and Maldonado, R and Fernández-Real, JM}, title = {Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways.}, journal = {Gut}, volume = {70}, number = {12}, pages = {2283-2296}, pmid = {33514598}, issn = {1468-3288}, mesh = {Adult ; Aged ; Amino Acids, Aromatic/*metabolism ; Animals ; Carbon/*metabolism ; Cross-Sectional Studies ; Fatty Liver/microbiology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; *Inhibition, Psychological ; Male ; Mice ; Middle Aged ; Obesity/*complications ; Phenotype ; Transcriptome ; }, abstract = {BACKGROUND: Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits.<br><br>METHODS: We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics.<br><br>RESULTS: An interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism (thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor's bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient's mice.<br><br>CONCLUSION: These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.}, }
@article {pmid33512409, year = {2021}, author = {Khan, N and Lindner, S and Gomes, ALC and Devlin, SM and Shah, GL and Sung, AD and Sauter, CS and Landau, HJ and Dahi, PB and Perales, MA and Chung, DJ and Lesokhin, AM and Dai, A and Clurman, A and Slingerland, JB and Slingerland, AE and Brereton, DG and Giardina, PA and Maloy, M and Armijo, GK and Rondon-Clavo, C and Fontana, E and Bohannon, L and Ramalingam, S and Bush, AT and Lew, MV and Messina, JA and Littmann, E and Taur, Y and Jenq, RR and Chao, NJ and Giralt, S and Markey, KA and Pamer, EG and van den Brink, MRM and Peled, JU}, title = {Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study.}, journal = {Blood}, volume = {137}, number = {11}, pages = {1527-1537}, pmid = {33512409}, issn = {1528-0020}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; R21 AG066388/AG/NIA NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; KL2 TR001115/TR/NCATS NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 CA203950/CA/NCI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Transplantation, Homologous ; }, abstract = {We previously described clinically relevant reductions in fecal microbiota diversity in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Recipients of high-dose chemotherapy and autologous HCT (auto-HCT) incur similar antibiotic exposures and nutritional alterations. To characterize the fecal microbiota in the auto-HCT population, we analyzed 1161 fecal samples collected from 534 adult recipients of auto-HCT for lymphoma, myeloma, and amyloidosis in an observational study conducted at 2 transplantation centers in the United States. By using 16S ribosomal gene sequencing, we assessed fecal microbiota composition and diversity, as measured by the inverse Simpson index. At both centers, the diversity of early pretransplant fecal microbiota was lower in patients than in healthy controls and decreased further during the course of transplantation. Loss of diversity and domination by specific bacterial taxa occurred during auto-HCT in patterns similar to those with allo-HCT. Above-median fecal intestinal diversity in the periengraftment period was associated with decreased risk of death or progression (progression-free survival hazard ratio, 0.46; 95% confidence interval, 0.26-0.82; P = .008), adjusting for disease and disease status. This suggests that further investigation into the health of the intestinal microbiota in auto-HCT patients and posttransplant outcomes should be undertaken.}, }
@article {pmid33511356, year = {2021}, author = {Helve, O and Dikareva, E and Stefanovic, V and Kolho, KL and Salonen, A and de Vos, WM and Andersson, S}, title = {Protocol for oral transplantation of maternal fecal microbiota to newborn infants born by cesarean section.}, journal = {STAR protocols}, volume = {2}, number = {1}, pages = {100271}, pmid = {33511356}, issn = {2666-1667}, mesh = {Cesarean Section ; *Fecal Microbiota Transplantation ; Female ; Humans ; Infant, Newborn ; Pregnancy ; }, abstract = {Infants born by cesarean section have an intestinal microbiota that differs from that of infants delivered vaginally. Here, we report a protocol for performing oral transplantation of maternal fecal microbiota to newborn infants born by elective cesarean section. The crucial step of this protocol is the health screening process. This protocol can only be applied to healthy mothers and infants. For complete details on the use and execution of this protocol, please refer to Korpela et al. (2020).}, }
@article {pmid33511048, year = {2020}, author = {Ridola, L and Faccioli, J and Nardelli, S and Gioia, S and Riggio, O}, title = {Hepatic Encephalopathy: Diagnosis and Management.}, journal = {Journal of translational internal medicine}, volume = {8}, number = {4}, pages = {210-219}, pmid = {33511048}, issn = {2450-131X}, abstract = {Type C hepatic encephalopathy (HE) is a brain dysfunction caused by severe hepatocellular failure or presence of portal-systemic shunts in patients with liver cirrhosis. In its subclinical form, called "minimal hepatic encephalopathy (MHE), only psychometric tests or electrophysiological evaluation can reveal alterations in attention, working memory, psychomotor speed and visuospatial ability, while clinical neurological signs are lacking. The term "covert" (CHE) has been recently used to unify MHE and Grade I HE in order to refer to a condition that is not unapparent but also non overt. "Overt" HE (OHE) is characterized by personality changes, progressive disorientation in time and space, acute confusional state, stupor and coma. Based on its time course, OHE can be divided in Episodic, Recurrent or Persistent. Episodic HE is generally triggered by one or more precipitant factors that should be found and treated. Unlike MHE, clinical examination and clinical decision are crucial for OHE diagnosis and West Haven criteria are widely used to assess the severity of neurological dysfunction. Primary prophylaxis of OHE is indicated only in the patient with gastrointestinal bleeding using non-absorbable antibiotics (Rifaximin) or non-absorbable disaccharides (Lactulose). Treatment of OHE is based on the identification and correction of precipitating factors and starting empirical ammonia-lowering treatment with Rifaximin and Lactulose (per os and enemas). The latter should be used for secondary prophylaxis, adding Rifaximin if HE becomes recurrent. In recurrent/persistent HE, the treatment options include fecal transplantation, TIPS revision and closure of eventual splenorenal shunts. Treatment of MHE should be individualized on a case-by-case basis.}, }
@article {pmid33510784, year = {2021}, author = {Xu, HM and Huang, HL and Zhou, YL and Zhao, HL and Xu, J and Shou, DW and Liu, YD and Zhou, YJ and Nie, YQ}, title = {Fecal Microbiota Transplantation: A New Therapeutic Attempt from the Gut to the Brain.}, journal = {Gastroenterology research and practice}, volume = {2021}, number = {}, pages = {6699268}, pmid = {33510784}, issn = {1687-6121}, abstract = {Gut dysbacteriosis is closely related to various intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT) is a biological therapy that entails transferring the gut microbiota from healthy individuals to patients in order to reconstruct the intestinal microflora in the latter. It has been proved to be an effective treatment for recurrent Clostridium difficile infection. Studies show that the gut microbiota plays an important role in the pathophysiology of neurological and psychiatric disorders through the microbiota-gut-brain axis. Therefore, reconstruction of the healthy gut microbiota is a promising new strategy for treating cerebral diseases. We have reviewed the latest research on the role of gut microbiota in different nervous system diseases as well as FMT in the context of its application in neurological, psychiatric, and other nervous system-related diseases (Parkinson's disease, Alzheimer's disease, multiple sclerosis, epilepsy, autism spectrum disorder, bipolar disorder, hepatic encephalopathy, neuropathic pain, etc.).}, }
@article {pmid33510783, year = {2021}, author = {Zhong, M and Buch, H and Wen, Q and Long, C and Cui, B and Zhang, F}, title = {Colonic Transendoscopic Enteral Tubing: Route for a Novel, Safe, and Convenient Delivery of Washed Microbiota Transplantation in Children.}, journal = {Gastroenterology research and practice}, volume = {2021}, number = {}, pages = {6676962}, pmid = {33510783}, issn = {1687-6121}, abstract = {AIM: Colonic transendoscopic enteral tubing (TET) has been used for delivering fecal microbiota transplantation by washed preparation since 2015, which was recently named as washed microbiota transplantation (WMT). However, there are few reports available regarding the feasibility and safety of these studies in low-age population. This study is aimed at evaluating the safety, feasibility, and value of colonic TET in 3-7 years old children.<br><br>METHODS: All patients aged 3-7 years who underwent colonic TET in our center for WMT or medication were prospectively evaluated. The feasibility and safety of TET were evaluated. A questionnaire was completed by the children's parents to evaluate the children's response to the colonic TET as well as the parent's satisfaction.<br><br>RESULTS: Forty-seven children were included (mean age 5 years). TET was implemented into the colon of all the patients, and the success rate of the procedure was 100%. The median retention time of TET tube within the colon was 6 (IQR 5-7) days in 45 patients with tube falling out spontaneously, and the maximum retention time was up to 21 days. Multivariate analysis demonstrated that endoscopic clip number (P = 0.009) was an independent contributing factor for the retaining time of tube. With increase in the number of large clips, the retention time of TET tube was prolonged. No discomfort was reported during injection of the microbiota or medication suspension through the TET tube. During the follow-up, no severe adverse events were observed. All children's parents were satisfied with TET. Interestingly, the proportion of children's parents choosing TET as the delivery way of WMT increased from 29.79% before to 70.21% after TET (P < 0.001).<br><br>CONCLUSIONS: This study, for the first time, demonstrates that colonic TET is a novel, safe, and convenient colonic delivery way for WMT and medication in children aged 3-7 years.}, }
@article {pmid33510660, year = {2020}, author = {Ghenciulescu, A and Park, RJ and Burnet, PWJ}, title = {The Gut Microbiome in Anorexia Nervosa: Friend or Foe?.}, journal = {Frontiers in psychiatry}, volume = {11}, number = {}, pages = {611677}, pmid = {33510660}, issn = {1664-0640}, abstract = {The human gut microbiome is emerging as a key modulator of homeostasis, with far-reaching implications for various multifactorial diseases, including anorexia nervosa (AN). Despite significant morbidity and mortality, the underlying mechanisms of this eating disorder are poorly understood, but the classical view defining AN as a purely psychiatric condition is increasingly being challenged. Accumulating evidence from comparative studies of AN and healthy fecal microbial composition reveals considerable low divergence and altered taxonomic abundance of the AN gut microbiome. When integrated with preclinical data, these findings point to a significant role of the gut microbiome in AN pathophysiology, via effects on host energy metabolism, intestinal permeability, immune function, appetite, and behavior. While complex causal relationships between genetic risk factors, dietary patterns and microbiome, and their relevance for AN onset and perpetuation have not been fully elucidated, preliminary clinical studies support the use of microbiome-based interventions such as fecal microbiota transplants and probiotics as adjuvants to standard AN therapies. Future research should aim to move from observational to mechanistic, as dissecting how specific microbial taxa interact with the host to impact the development of AN could help design novel therapeutic approaches that more effectively address the severe comorbidities and high relapse rate of this serious disorder.}, }
@article {pmid33508620, year = {2021}, author = {Li, X and Kang, Y and Huang, Y and Xiao, Y and Song, L and Lu, S and Ren, Z}, title = {A strain of Bacteroides thetaiotaomicron attenuates colonization of Clostridioides difficile and affects intestinal microbiota and bile acids profile in a mouse model.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {137}, number = {}, pages = {111290}, doi = {10.1016/j.biopha.2021.111290}, pmid = {33508620}, issn = {1950-6007}, mesh = {Animals ; Bacteroides thetaiotaomicron/*growth &amp; development ; Bile Acids and Salts/*metabolism ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/metabolism/microbiology/*prevention &amp; control ; Colon/*microbiology ; Disease Models, Animal ; Feces/chemistry/microbiology ; Female ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Mice, Inbred C57BL ; *Probiotics ; Mice ; }, abstract = {Clostridioides difficile infection (CDI) is a growing global public health threat. While fecal microbiota transplantation (FMT) is an effective therapy for CDI, a number of challenges limit its application. Studies suggest that probiotics may be a promising alternative therapy. In the current study, we evaluated whether Bacteroides thetaiotaomicron (B. thetaiotaomicron) would inhibit colonization of toxigenic BI/NAP1/027 C. difficile in a mouse model. We found that B. thetaiotaomicron administration decreased the copies of C. difficile and inhibited inflammation in the colon. 16S rRNA sequencing showed that B. thetaiotaomicron administration was associated with a significantly increased relative abundance of Bacteroidetes and decreased level of Proteobacteria, leading to the reversal of the effect of antibiotics treatment and C. difficile infection on microbiota. B. thetaiotaomicron administration was associated with increases in the concentrations of alpha-muricholic acid, beta-muricholic acid, 12 ketolithocholic acid, and deoxycholic acid which are known to inhibit the growth of C. difficile, as well as reductions in the level of taurocholic acid, which promotes germination of C. difficile. Altered profile of major high abundance bile acids by B. thetaiotaomicron administration was similar to that with FMT treatment. Based on these results, we proposed the concept of "the ratio of promotion/inhibition BAs" which would advance our understanding of the relation of C. difficile and BAs.}, }
@article {pmid33508265, year = {2021}, author = {Ait Yahia, S and Audousset, C and Alvarez-Simon, D and Vorng, H and Togbe, D and Marquillies, P and Delacre, M and Rose, S and Bouscayrol, H and Rifflet, A and Quesniaux, V and Boneca, IG and Chamaillard, M and Tsicopoulos, A}, title = {NOD1 sensing of house dust mite-derived microbiota promotes allergic experimental asthma.}, journal = {The Journal of allergy and clinical immunology}, volume = {148}, number = {2}, pages = {394-406}, doi = {10.1016/j.jaci.2020.12.649}, pmid = {33508265}, issn = {1097-6825}, mesh = {Animals ; Asthma/chemically induced/genetics/*immunology/microbiology ; Disease Models, Animal ; Female ; Gastrointestinal Microbiome/*immunology ; Mice ; Mice, Knockout ; Nod1 Signaling Adaptor Protein/genetics/*immunology ; Pyroglyphidae/*immunology ; Signal Transduction/genetics/*immunology ; }, abstract = {BACKGROUND: Asthma severity has been linked to exposure to gram-negative bacteria from the environment that are recognized by NOD1 receptor and are present in house dust mite (HDM) extracts. NOD1 polymorphism has been associated with asthma.<br><br>OBJECTIVE: We sought to evaluate whether either host or HDM-derived microbiota may contribute to NOD1-dependent disease severity.<br><br>METHODS: A model of HDM-induced experimental asthma was used and the effect of NOD1 deficiency was evaluated. Contribution of host microbiota was evaluated by fecal transplantation. Contribution of HDM-derived microbiota was assessed by 16S ribosomal RNA sequencing, mass spectrometry analysis, and peptidoglycan depletion of the extracts.<br><br>RESULTS: In this model, loss of the bacterial sensor NOD1 and its adaptor RIPK2 improved asthma features. Such inhibitory effect was not related to dysbiosis caused by NOD1 deficiency, as shown by fecal transplantation of Nod1-deficient microbiota to wild-type germ-free mice. The 16S ribosomal RNA gene sequencing and mass spectrometry analysis of HDM allergen, revealed the presence of some muropeptides from gram-negative bacteria that belong to the Bartonellaceae family. While such HDM-associated muropeptides were found to activate NOD1 signaling in epithelial cells, peptidoglycan-depleted HDM had a decreased ability to instigate asthma in&#xa0;vivo.<br><br>CONCLUSIONS: These data show that NOD1-dependent sensing of HDM-associated gram-negative bacteria aggravates the severity of experimental asthma, suggesting that inhibiting the NOD1 signaling pathway may be a therapeutic approach to treating asthma.}, }
@article {pmid33506928, year = {2021}, author = {Nakov, R and Lyutakov, I and Mitkova, A and Gerova, V and Petkova, V and Giragosyan, S and Vatcheva-Dobrevska, R and Kaneva, R and Nakov, V}, title = {Establishment of the first stool bank in an Eastern European country and the first series of successful fecal microbiota transplantations in Bulgaria.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {1}, pages = {390-396}, doi = {10.26355/eurrev_202101_24406}, pmid = {33506928}, issn = {2284-0729}, mesh = {Adult ; Aged ; Bulgaria ; Colonoscopy ; Enterocolitis, Pseudomembranous/*therapy ; Europe ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Middle Aged ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: For safe implementation and broader application of fecal microbiota transplantation (FMT), quality controlled stool banking is a must. Establishing a stool bank is a complex, time-consuming, and expensive process, making it a real challenge in an Eastern European country. We aimed to establish the first stool bank in Eastern Europe - in Bulgaria.<br><br>SUBJECTS AND METHODS: A multidisciplinary team of gastroenterologists, microbiologists, infectionists, and geneticists was set up. We used a questionnaire based on the First European FMT Consensus in order to recruit possible stool donors. Laboratory blood and stool tests were performed on all potential donors.<br><br>RESULTS: Between October 2018 and April 2019, 112 donor volunteers completed a questionnaire; 70 (62.5%) were excluded, mainly because of age above 50, an unhealthy BMI, and risk behavior. Fourty-two (37.5%) donor candidates were invited for laboratory testing of blood and feces, of which 12 (28.6%) passed this screening. Of 12 donors, 4 (33%) failed at the following screening test, which is performed every 3-6 months. Finally, 8 (7.14%) active donors were enrolled. Ten successful FMTs were performed on patients with recurrent Clostridium difficile infection.<br><br>CONCLUSIONS: Even though we found many healthy volunteers, only a low percentage (7.14%) of them were suitable to become feces donors. Establishing a stool bank in an Eastern European country is essential for making FMT safe and more popular as a treatment method, finding further implementation and regulation of FMT and supporting physicians offering this treatment to their patients.}, }
@article {pmid33505139, year = {2020}, author = {Qi, X and Yang, M and Stenberg, J and Dey, R and Fogwe, L and Alam, MS and Kimchi, ET and Staveley-O'Carroll, KF and Li, G}, title = {Gut microbiota mediated molecular events and therapy in liver diseases.}, journal = {World journal of gastroenterology}, volume = {26}, number = {48}, pages = {7603-7618}, pmid = {33505139}, issn = {2219-2840}, support = {R01 CA208396/CA/NCI NIH HHS/United States ; }, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Liver ; *Non-alcoholic Fatty Liver Disease/therapy ; *Probiotics/therapeutic use ; }, abstract = {Gut microbiota is a community of microorganisms that reside in the gastrointestinal tract. An increasing number of studies has demonstrated that the gut-liver axis plays a critical role in liver homeostasis. Dysbiosis of gut microbiota can cause liver diseases, including nonalcoholic fatty liver disease and alcoholic liver disease. Preclinical and clinical investigations have substantiated that the metabolites and other molecules derived from gut microbiota and diet interaction function as mediators to cause liver fibrosis, cirrhosis, and final cancer. This effect has been demonstrated to be associated with dysregulation of intrahepatic immunity and liver metabolism. Targeting these findings have led to the development of novel preventive and therapeutic strategies. Here, we review the cellular and molecular mechanisms underlying gut microbiota-mediated impact on liver disease. We also summarize the advancement of gut microbiota-based therapeutic strategies in the control of liver diseases.}, }
@article {pmid33504491, year = {2022}, author = {Zhang, T and Sun, P and Geng, Q and Fan, H and Gong, Y and Hu, Y and Shan, L and Sun, Y and Shen, W and Zhou, Y}, title = {Disrupted spermatogenesis in a metabolic syndrome model: the role of vitamin A metabolism in the gut-testis axis.}, journal = {Gut}, volume = {71}, number = {1}, pages = {78-87}, pmid = {33504491}, issn = {1468-3288}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Disease Models, Animal ; Dysbiosis/physiopathology ; Gastrointestinal Microbiome/*physiology ; Male ; Metabolic Syndrome/*physiopathology ; Metabolome ; Sheep ; Spermatogenesis/*physiology ; Testis/*physiology ; Vitamin A/*metabolism ; }, abstract = {OBJECTIVE: Effects of the diet-induced gut microbiota dysbiosis reach far beyond the gut. We aim to uncover the direct evidence involving the gut-testis axis in the aetiology of impaired spermatogenesis.<br><br>DESIGN: An excessive-energy diet-induced metabolic syndrome (MetS) sheep model was established. The testicular samples, host metabolomes and gut microbiome were analysed. Faecal microbiota transplantation (FMT) confirmed the linkage between gut microbiota and spermatogenesis.<br><br>RESULTS: We demonstrated that the number of arrested spermatogonia was markedly elevated by using 10&#xd7; single-cell RNA-seq in the MetS model. Furthermore, through using metabolomics profiling and 16S rDNA-seq, we discovered that the absorption of vitamin A in the gut was abolished due to a notable reduction of bile acid levels, which was significantly associated with reduced abundance of Ruminococcaceae_NK4A214_group. Notably, the abnormal metabolic effects of vitamin A were transferable to the testicular cells through the circulating blood, which contributed to abnormal spermatogenesis, as confirmed by FMT.<br><br>CONCLUSION: These findings define a starting point for linking the testicular function and regulation of gut microbiota via host metabolomes and will be of potential value for the treatment of male infertility in MetS.}, }
@article {pmid33504365, year = {2021}, author = {Hao, X and Shang, X and Liu, J and Chi, R and Zhang, J and Xu, T}, title = {The gut microbiota in osteoarthritis: where do we stand and what can we do?.}, journal = {Arthritis research &amp; therapy}, volume = {23}, number = {1}, pages = {42}, pmid = {33504365}, issn = {1478-6362}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; *Osteoarthritis/therapy ; Quality of Life ; }, abstract = {Osteoarthritis (OA) is one of the most frequent musculoskeletal diseases characterized by degeneration of articular cartilage, subchondral bone remodeling, and synovial membrane inflammation, which is a leading cause of global disability, morbidity, and decreased quality of life. Interpreting the potential mechanisms of OA pathogenesis is essential for developing novel prevention and disease-modifying therapeutic interventions. Gut microbiota is responsible for a series of metabolic, immunological, and structural and neurological functions, potentially elucidating the heterogeneity of OA phenotypes and individual features. In this narrative review, we summarized research evidence supporting the hypothesis of a "gut-joint axis" and the interaction between gut microbiota and the OA-relevant factors, including age, gender, genetics, metabolism, central nervous system, and joint injury, elucidating the underlying mechanisms of this intricate interaction. In the context, we also speculated the promising manipulation of gut microbiota in OA management, such as exercise and fecal microbiota transplantation (FMT), highlighting the clinical values of gut microbiota. Additionally, future research directions, such as more convincing studies by the interventions of gut microbiota, the gene regulation of host contributing to or attributed to the specific phenotypes of gut microbiota related to OA, and the relevance of distinct cell subgroups to gut microbiota, are expected. Moreover, gut microbiota is also the potential biomarker related to inflammation and gut dysbiosis that is able to predict OA progression and monitor the efficacy of therapeutic intervention.}, }
@article {pmid33504332, year = {2021}, author = {Littlejohn, P and Finlay, BB}, title = {When a pandemic and an epidemic collide: COVID-19, gut microbiota, and the double burden of malnutrition.}, journal = {BMC medicine}, volume = {19}, number = {1}, pages = {31}, pmid = {33504332}, issn = {1741-7015}, support = {FDN-159935//CIHR/Canada ; }, mesh = {Animals ; COVID-19/*epidemiology ; Developing Countries ; Diet ; Dysbiosis ; Food Insecurity ; *Gastrointestinal Microbiome ; Health Behavior ; Humans ; Income ; Malnutrition/*epidemiology ; Mice ; Obesity/epidemiology ; Overweight/epidemiology ; *Pandemics ; Poverty ; }, abstract = {BACKGROUND: It is estimated that the COVID-19 pandemic will drastically increase all forms of malnutrition. Of particular concern, yet understated, is the potential to increase the double burden of malnutrition (DBM) epidemic. This coexistence of undernutrition together with overweight and obesity, or diet-related non-communicable disease (NCD), within low- to middle-income countries (LMICs) is increasing rapidly. Although multiple factors contribute to the DBM, food insecurity (FI) and gut microbiota dysbiosis play a crucial role. Both under- and overnutrition have been shown to be a consequence of food insecurity. The gut microbiota has also been recently implicated in playing a role in under- and overnutrition, with altered community structure and function common to both. The pandemic has already caused significant shifts in food availability which has immediate effects on the gut microbiome. In this opinion paper, we discuss how COVID-19 may indirectly exacerbate the DBM through food insecurity and the gut microbiome.<br><br>MAIN TEXT: The World Food Programme (WFP) estimates that 265 million people in LMICs will experience acute hunger in 2020 due to the pandemic, nearly doubling the original projection of 135 million. Global border closures to food trade, loss of food production, and stark decline in household income will exacerbate starvation while simultaneously necessitating that families resort to calorie-dense, nutrient-poor foods, thereby increasing obesity. While food insecurity, which is the persistent lack of consistent access to adequate and nutrient-rich foods, will primarily drive nutrition behavior, the gut microbiome is perhaps a key biological mechanism. Numerous human and animal studies describe low diversity and an increase in inflammatory species as characteristic features of the undernourished and overnourished gut microbiota. Indeed, fecal transplant studies show that microbiota transfer from undernourished and overnourished humans to germ-free mice lacking a microbiome transfers the physical and metabolic phenotype, suggesting a causal role for the microbiota in under- and overnutrition. The observed microbiome dysbiosis within severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coupled with the DBM presents a viscous cycle.<br><br>CONCLUSION: Low- to mid-income countries will likely see an increase in the DBM epidemic. Providing access to nutritious foods and protecting individuals' gut microbiome to "flatten the curve" of the DBM trajectory should be prioritized.}, }
@article {pmid33502898, year = {2021}, author = {Hirten, RP and Sands, BE}, title = {New Therapeutics for Ulcerative Colitis.}, journal = {Annual review of medicine}, volume = {72}, number = {}, pages = {199-213}, doi = {10.1146/annurev-med-052919-120048}, pmid = {33502898}, issn = {1545-326X}, mesh = {Anti-Ulcer Agents/*therapeutic use ; Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Hyperbaric Oxygenation/*methods ; Immunologic Factors/*therapeutic use ; Janus Kinase Inhibitors/*therapeutic use ; Sphingosine 1 Phosphate Receptor Modulators/*therapeutic use ; }, abstract = {Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon with a variable course. Despite advances in treatment, only approximately 40% of patients achieve clinical remission at the end of a year, prompting the exploration of new treatment modalities. This review explores novel therapeutic approaches to UC, including promising drugs in various stages of development, efforts to maximize the efficacy of currently available treatment options, and non-medication-based modalities. Treatment approaches which show promise in impacting the future of UC management are highlighted.}, }
@article {pmid33501942, year = {2021}, author = {Karjalainen, EK and Renkonen-Sinisalo, L and Satokari, R and Mustonen, H and Ristimäki, A and Arkkila, P and Lepistö, AH}, title = {Fecal Microbiota Transplantation in Chronic Pouchitis: A Randomized, Parallel, Double-Blinded Clinical Trial.}, journal = {Inflammatory bowel diseases}, volume = {27}, number = {11}, pages = {1766-1772}, pmid = {33501942}, issn = {1536-4844}, mesh = {Anti-Bacterial Agents/therapeutic use ; Chronic Disease ; *Colitis, Ulcerative/complications/drug therapy ; *Fecal Microbiota Transplantation ; Humans ; *Pouchitis/etiology/therapy ; }, abstract = {BACKGROUND: In ulcerative colitis, a pouchitis is the most common long-term adverse effect after proctocolectomy and ileal pouch-anal anastomosis. Approximately 5% of patients develop chronic antibiotic-dependent or antibiotic-refractory pouchitis without any effective treatment. The aim of this trial was to investigate the efficacy and safety of fecal microbiota transplantation in the treatment of chronic pouchitis.<br><br>METHODS: This was a single-center, double-blinded, parallel group trial comparing donor fecal microbiota transplantation with placebo (autologous transplant) in chronic pouchitis. Twenty-six patients were recruited at the Helsinki University Hospital between December 2017 and August 2018 and were randomly allocated a 1:1 ratio to either donor fecal microbiota transplantation or placebo. The protocol included 2 transplantations into the pouch on weeks 0 and 4, and patients were followed up for 52 weeks.<br><br>RESULTS: Nine patients in the intervention group and 8 patients in the placebo group relapsed during the 52-week follow-up, and the relapse-free survival did not differ between the groups (P = 0.183, log-rank; hazard ratio, 1.90 [95% confidence interval, 0.73-4.98; P = 0.190]). In the subgroup analysis of patients using continuous antibiotics before the study, the relapse-free survival was shorter in the intervention group (P = 0.004, log-rank; hazard ratio, 13.08 [95% confidence interval, 1.47-116.60; P = 0.021]). No major adverse effects were reported.<br><br>CONCLUSIONS: The fecal microbiota transplantation treatment regime used in our study was not effective in the treatment of chronic pouchitis. The safety profile of fecal microbiota transplantation was good.<br><br>CLINICALTRIALS.GOV IDENTIFIER: NCT03378921.}, }
@article {pmid33501941, year = {2021}, author = {Dalal, RS and Allegretti, JR}, title = {Fecal Microbiota Transplantation for Chronic Pouchitis: Promising Novel Therapeutic or Lost Cause?.}, journal = {Inflammatory bowel diseases}, volume = {27}, number = {11}, pages = {1873-1875}, pmid = {33501941}, issn = {1536-4844}, support = {T32 DK007533/DK/NIDDK NIH HHS/United States ; }, mesh = {*Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Humans ; *Pouchitis/therapy ; }, }
@article {pmid33501940, year = {2021}, author = {Karjalainen, EK and Renkonen-Sinisalo, L and Satokari, R and Mustonen, H and Ristimäki, A and Arkkila, P and Lepistö, AH}, title = {Author's Reply: Fecal Microbiota Transplantation for Chronic Pouchitis: Promising Novel Therapeutic or Lost Cause?.}, journal = {Inflammatory bowel diseases}, volume = {27}, number = {7}, pages = {e79-e80}, doi = {10.1093/ibd/izab003}, pmid = {33501940}, issn = {1536-4844}, mesh = {*Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Humans ; *Pouchitis/therapy ; }, }
@article {pmid33501716, year = {2021}, author = {Chan, S and Morrison, M and Hawley, CM and Campbell, SB and Francis, RS and Isbel, NM and Pascoe, EM and Johnson, DW}, title = {Characteristics of the gastrointestinal microbiota in paired live kidney donors and recipients.}, journal = {Nephrology (Carlton, Vic.)}, volume = {26}, number = {5}, pages = {471-478}, doi = {10.1111/nep.13853}, pmid = {33501716}, issn = {1440-1797}, support = {APP1168186//Australian Health and Medical Research Council/ ; Microba Research Grant//Microba/ ; Jacquot Research Establishment//Royal Australasian College of Physicians/ ; }, mesh = {Adult ; Cohort Studies ; Female ; *Gastrointestinal Microbiome ; Humans ; *Kidney Transplantation ; Living Donors ; Male ; Middle Aged ; Transplant Recipients ; }, abstract = {BACKGROUND: There are few studies that have examined whether dysbiosis occurs in kidney donors and transplant recipients following kidney transplant surgery.<br><br>AIM: To ascertain whether changes occur in the gastrointestinal microbiota of the kidney donor and recipient following kidney transplantation.<br><br>METHODS: Kidney transplant recipients and their donors were prospectively enrolled in a pilot study to collect one faecal sample prior to, and another faecal sample between four to eight weeks following surgery. Gastrointestinal microbiota richness, Shannon diversity measures and functional assessments of kidney donors and recipients were analysed via metagenomic sequencing.<br><br>RESULTS: The study included 12 donors (median age 56 years, 6 females) and 12 recipients (median age 51 years, 3 females). Donor microbiota showed no significant changes in gastrointestinal microbiota richness, Shannon diversity, or functional assessments before and after nephrectomy. Recipient microbiota was altered post-transplant, reflected in reductions of the mean (&#xb1;SD) richness values (156 &#xb1; 46.5 to 116 &#xb1; 38.6, p = 0.002), and Shannon diversity (3.57 &#xb1; 0.49 to 3.14 &#xb1; 0.52, p = 0.007), and a dramatic increase in Roseburia spp. abundance post-transplant (26-fold increase from 0.16 &#xb1; 0.0091 to 4.6 &#xb1; 0.3; p = 0.006; FDR = 0.12). Functionally, the post-transplant microbial community shifted towards those taxa using the glycolysis pathway (1.2-fold increase; p = 0.02; FDR = 0.26) for energy metabolism, while those functions involved with reactive oxygen species degradation decreased (2.6-fold; p = 0.006; FDR = 0.14).<br><br>CONCLUSION: Live donor kidney transplantation and standard care post-transplant result in significant alterations in gut microbiota richness, diversity, composition and functional parameters in kidney transplant recipients but not in their kidney donors.}, }
@article {pmid33501400, year = {2020}, author = {Utay, NS and Monczor, AN and Somasunderam, A and Lupo, S and Jiang, ZD and Alexander, AS and Finkelman, M and Vigil, KJ and Lake, JE and Hanson, B and DuPont, HL and Arduino, RC}, title = {Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV.}, journal = {Pathogens &amp; immunity}, volume = {5}, number = {1}, pages = {364-381}, pmid = {33501400}, issn = {2469-2964}, abstract = {BACKGROUND: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis.<br><br>METHODS: Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured.<br><br>RESULTS: Median age at week 0 was 39 years, CD4[+] T cell count 496 cells/mm[3], HIV RNA levels <20 copies/mL. FMT was safe and well-tolerated. &#x3b1; diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest &#x3b1; diversity at week 0. At week 26, &#x3b1; diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low &#x3b1; diversity that improved between weeks 0 and 6 with a shift in distribution.<br><br>CONCLUSIONS: Weekly FMT was safe and well-tolerated. &#x3b1; diversity increased in participants with the lowest baseline &#x3b1; diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560.}, }
@article {pmid33500411, year = {2021}, author = {Uzan-Yulzari, A and Turta, O and Belogolovski, A and Ziv, O and Kunz, C and Perschbacher, S and Neuman, H and Pasolli, E and Oz, A and Ben-Amram, H and Kumar, H and Ollila, H and Kaljonen, A and Isolauri, E and Salminen, S and Lagström, H and Segata, N and Sharon, I and Louzoun, Y and Ensenauer, R and Rautava, S and Koren, O}, title = {Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {443}, pmid = {33500411}, issn = {2041-1723}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Bacterial Infections/*drug therapy ; Body Height/drug effects/physiology ; Body Mass Index ; Body Weight/drug effects/physiology ; Child ; Child, Preschool ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/*drug effects/physiology ; Germ-Free Life ; Growth Disorders/*chemically induced/microbiology/physiopathology ; Humans ; Infant, Newborn ; Intestinal Mucosa/microbiology ; Male ; Mice ; Pregnancy ; Risk Factors ; Sex Factors ; }, abstract = {Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index.}, }
@article {pmid33499991, year = {2020}, author = {Sidiropoulos, DN and Al-Ghalith, GA and Shields-Cutler, RR and Ward, TL and Johnson, AJ and Vangay, P and Knights, D and Kashyap, PC and Xian, Y and Ramer-Tait, AE and Clayton, JB}, title = {Wild primate microbiomes prevent weight gain in germ-free mice.}, journal = {Animal microbiome}, volume = {2}, number = {1}, pages = {16}, pmid = {33499991}, issn = {2524-4671}, support = {R01 DK114007/DK/NIDDK NIH HHS/United States ; T32 DA007097/DA/NIDA NIH HHS/United States ; T32 DA007097-32/DA/NIDA NIH HHS/United States ; }, abstract = {BACKGROUND: The gut microbiome harbors trillions of bacteria that play a major role in dietary nutrient extraction and host metabolism. Metabolic diseases such as obesity and diabetes are associated with shifts in microbiome composition and have been on the rise in Westernized or highly industrialized countries. At the same time, Westernized diets low in dietary fiber have been shown to cause loss of gut microbial diversity. However, the link between microbiome composition, loss of dietary fiber, and obesity has not been well defined.<br><br>RESULTS: To study the interactions between gut microbiota, dietary fiber, and weight gain, we transplanted captive and wild douc gut microbiota into germ-free mice and then exposed them to either a high- or low-fiber diet. The group receiving captive douc microbiota gained significantly more weight, regardless of diet, while mice receiving a high-fiber diet and wild douc microbiota remained lean. In the presence of a low-fiber diet, the wild douc microbiota partially prevented weight gain. Using 16S rRNA gene amplicon sequencing we identified key bacterial taxa in each group, specifically a high relative abundance of Bacteroides and Akkermansia in captive douc FMT mice and a higher relative abundance of Lactobacillus and Clostridium in the wild douc FMT mice.<br><br>CONCLUSIONS: In the context of our germ-free mouse experiment, wild douc microbiota could serve as a reservoir for microbes for cross-species transplants. Our results suggest that wild douc microbiota are tailored to diverse fiber diets and can prevent weight gain when exposed to a native diet.}, }
@article {pmid33499964, year = {2020}, author = {Legrand, TPRA and Catalano, SR and Wos-Oxley, ML and Wynne, JW and Weyrich, LS and Oxley, APA}, title = {Antibiotic-induced alterations and repopulation dynamics of yellowtail kingfish microbiota.}, journal = {Animal microbiome}, volume = {2}, number = {1}, pages = {26}, pmid = {33499964}, issn = {2524-4671}, support = {2016-200.30//Department of Agriculture, Australian Government/ ; RnD4Profit 14-01-027//Fisheries Research and Development Corporation/ ; }, abstract = {BACKGROUND: The use of antibiotics in aquaculture is a common infection treatment and is increasing in some sectors and jurisdictions. While antibiotic treatment can negatively shift gut bacterial communities, recovery and examination of these communities in fish of commercial importance is not well documented. Examining the impacts of antibiotics on farmed fish microbiota is fundamental for improving our understanding and management of healthy farmed fish. This work assessed yellowtail kingfish (Seriola lalandi) skin and gut bacterial communities after an oral antibiotic combination therapy in poor performing fish that displayed signs of enteritis over an 18-day period. In an attempt to promote improved bacterial re-establishment after antibiotic treatment, faecal microbiota transplantation (FMT) was also administered via gavage or in the surrounding seawater, and its affect was evaluated over 15 days post-delivery.<br><br>RESULTS: Antibiotic treatment greatly perturbed the global gut bacterial communities of poor-performing fish - an effect that lasted for up to 18&#x2009;days post treatment. This perturbation was marked by a significant decrease in species diversity and evenness, as well as a concomitant increase in particular taxa like an uncultured Mycoplasmataceae sp., which persisted and dominated antibiotic-treated fish for the entire 18-day period. The skin-associated bacterial communities were also perturbed by the antibiotic treatment, notably within the first 3&#x2009;days; however, this was unlike the gut, as skin microbiota appeared to shift towards a more 'normal' (though disparate) state after 5&#x2009;days post antibiotic treatment. FMT was only able to modulate the impacts of antibiotics in some individuals for a short time period, as the magnitude of change varied substantially between individuals. Some fish maintained certain transplanted gut taxa (i.e. present in the FMT inoculum; namely various Aliivibrio related ASVs) at Day 2 post FMT, although these were lost by Day 8 post FMT.<br><br>CONCLUSION: As we observed notable, prolonged perturbations induced by antibiotics on the gut bacterial assemblages, further work is required to better understand the processes/dynamics of their re-establishment following antibiotic exposure. In this regard, procedures like FMT represent a novel approach for promoting improved microbial recovery, although their efficacy and the factors that support their success requires further investigation.}, }
@article {pmid33498428, year = {2021}, author = {Kampouri, E and Croxatto, A and Prod'hom, G and Guery, B}, title = {Clostridioides difficile Infection, Still a Long Way to Go.}, journal = {Journal of clinical medicine}, volume = {10}, number = {3}, pages = {}, pmid = {33498428}, issn = {2077-0383}, abstract = {Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them.}, }
@article {pmid33497754, year = {2021}, author = {Settanni, CR and Ianiro, G and Bibbò, S and Cammarota, G and Gasbarrini, A}, title = {Gut microbiota alteration and modulation in psychiatric disorders: Current evidence on fecal microbiota transplantation.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {109}, number = {}, pages = {110258}, doi = {10.1016/j.pnpbp.2021.110258}, pmid = {33497754}, issn = {1878-4216}, mesh = {Brain-Gut Axis/*physiology ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Mental Disorders/microbiology/*therapy ; Treatment Outcome ; }, abstract = {The micro-organisms residing within the gastrointestinal tract, namely gut microbiota, form a dynamic population proper of each individual, mostly composed by bacteria which co-evolved symbiotically with human species. The advances of culture-independent techniques allowed the understanding of the multiple functions of the gut microbiota in human physiology and disease, the latter often recognising a predisposing condition in an imbalanced intestinal microbial ecosystem (dysbiosis). A complex mutual interconnection between the central nervous system (CNS), the intestine and the gut microbiota, known as "microbiota-gut-brain axis", has been hypothesized to play a pivotal role in maintaining central and peripheral functions, as well as mental health. Thus, dysbiosis with specific microbiota imbalances seems to be strongly associated with the onset psychiatric disorders by altering neurodevelopment, enhancing neurodegeneration, affecting behaviour and mood. Fecal microbiota transplantation (FMT) consists of transferring the fecal matter from a donor into the gastrointestinal tract of a recipient, and it is used to quickly modulate the gut microbiota. This review focuses on the uses of FMT in psychiatric disorders. FMT has been used to induce dysbiosis and to study the disease development, or to heal dysbiosis-related mental disorders. Overall, FMT of impaired microbiota resulted effective in enhancing psychiatric-like disturbances (mainly depression and anxiety) in recipient animals, plausibly by impairing immune system, inflammatory and metabolic pathways, neurochemical processes and neuro-transmission. On the other side, preclinical and clinical data suggest that reversing or mitigating dysbiosis seems a promising strategy to restore behavioural impairments or to obtain psychiatric symptom relief. However, current evidence is limited by the lack of procedural standardization, the paucity of human studies in the vastity of psychiatric conditions and the need of a microbiota-targeted donor-recipient matching.}, }
@article {pmid33496893, year = {2021}, author = {Tariq, R and Hayat, M and Pardi, D and Khanna, S}, title = {Predictors of failure after fecal microbiota transplantation for recurrent Clostridioides difficile infection: a systematic review and meta-analysis.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {40}, number = {7}, pages = {1383-1392}, pmid = {33496893}, issn = {1435-4373}, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Treatment Failure ; }, abstract = {Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI), with ~15% 1-year recurrence rate. Small studies have identified variable risk factors associated with FMT failure. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of FMT failure. A systematic search of Medline, Embase, and Web of Science was performed from January 2013 up to June 2020. Meta-analyses were performed using random-effects models and pooled adjusted odds ratios for risk factors reported in ≥2 studies were calculated. Overall, 2671 patients with recurrent CDI who underwent FMT in 12 studies were included. FMT failure occurred in 454 patients (16.9%) with median follow-up of 3 months (range 2-7.7 months). A total of 9 risk factors were identified in ≥2 studies. Meta-analysis showed that use of non- CDI antibiotics, presence of inflammatory bowel disease, poor quality of bowel preparation, CDI-related hospitalization before FMT, inpatient FMT, and severe CDI were associated with statistically significant increased risk of failure after FMT. Increasing age, female gender, and immunocompromised status were not associated with increased risk for FMT failure. Several risk factors (both modifiable and non-modifiable) are associated with FMT failure. Lower use of antibiotics in the post-FMT period and good bowel preparation at the time of FMT are associated with lower risk of failure after FMT. Additionally, patients with non-modifiable risk factors should be counseled to be particularly alert about recurrent symptoms after FMT.}, }
@article {pmid33495644, year = {2021}, author = {Graham, AL}, title = {Naturalizing mouse models for immunology.}, journal = {Nature immunology}, volume = {22}, number = {2}, pages = {111-117}, pmid = {33495644}, issn = {1529-2916}, mesh = {*Allergy and Immunology ; Animals ; Biological Evolution ; *Biomedical Research ; Biota ; *Environment ; Host-Pathogen Interactions ; Immune System/microbiology/*physiology ; *Immunity ; Mice ; Models, Animal ; Phenotype ; }, abstract = {Laboratory mice have provided invaluable insight into mammalian immune systems. Yet the immune phenotypes of mice bred and maintained in conventional laboratory conditions often differ from the immune phenotypes of wild mammals. Recent work to naturalize the environmental experience of inbred laboratory mice-to take them where the wild things are (to borrow a phrase from Maurice Sendak), via approaches such as construction of exposure histories, provision of fecal transplants or surrogate mothering by wild mice, and rewilding-is poised to expand understanding, complementing genetic and phylogenetic research on how natural selection has shaped mammalian immune systems while improving the translational potential of mouse research.}, }
@article {pmid33493658, year = {2021}, author = {Fang, Y and Zhang, J and Zhu, S and He, M and Ma, S and Jia, Q and Sun, Q and Song, L and Wang, Y and Duan, L}, title = {Berberine ameliorates ovariectomy-induced anxiety-like behaviors by enrichment in equol generating gut microbiota.}, journal = {Pharmacological research}, volume = {165}, number = {}, pages = {105439}, doi = {10.1016/j.phrs.2021.105439}, pmid = {33493658}, issn = {1096-1186}, mesh = {Animals ; Anxiety/*drug therapy/etiology/*metabolism ; Berberine/pharmacology/*therapeutic use ; Equol/*metabolism ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Ovariectomy/*adverse effects ; Rats ; Rats, Sprague-Dawley ; }, abstract = {The gut microbiota is recognized as a promising therapeutic target for anxiety. Berberine (BBR) has shown efficacy in the treatment of diseases such as postmenopausal osteoporosis, obesity, and type 2 diabetes through regulating the gut microbiota. However, the effects of BBR on postmenopausal anxiety are still unclear. The purpose of the study is to test whether BBR ameliorates anxiety by modulating intestinal microbiota under estrogen-deficient conditions. Experimental anxiety was established in specific pathogen-free (SPF) ovariectomized (OVX) rats, which were then treated with BBR for 4 weeks before undergoing behavioral tests. Open field and elevated plus maze tests demonstrated that BBR treatment significantly ameliorated anxiety-like behaviors of OVX rats compared with vehicle-treated counterparts. Moreover, as demonstrated by 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC/MS) analysis, BBR-treated OVX rats harbored a higher abundance of beneficial gut microbes, such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia, and exhibited increased equol generation. Notably, gavage feeding of BBR had no significant anti-anxiety effects on germ-free (GF) rats that underwent ovariectomy, whereas GF rats transplanted with fecal microbiota from SPF rats substantially phenocopied the donor rats in terms of anxiety-like symptoms and isoflavone levels. This study indicates that the gut microbiota is critical in the treatment of ovariectomy-aggravated anxiety, and that BBR modulation of the gut microbiota is a promising therapeutic strategy for treating postmenopausal symptoms of anxiety.}, }
@article {pmid33493503, year = {2021}, author = {Margolis, KG and Cryan, JF and Mayer, EA}, title = {The Microbiota-Gut-Brain Axis: From Motility to Mood.}, journal = {Gastroenterology}, volume = {160}, number = {5}, pages = {1486-1501}, pmid = {33493503}, issn = {1528-0012}, support = {R01 DK048351/DK/NIDDK NIH HHS/United States ; R01 DK126644/DK/NIDDK NIH HHS/United States ; R01 NS015547/NS/NINDS NIH HHS/United States ; }, mesh = {*Affect ; Animals ; Bacteria/*growth &amp; development/metabolism ; Brain/metabolism/*physiopathology ; Central Nervous System Diseases/*microbiology/physiopathology/psychology/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/*microbiology/physiopathology/psychology/therapy ; *Gastrointestinal Microbiome ; *Gastrointestinal Motility ; Humans ; Intestines/*innervation/*microbiology ; }, abstract = {The gut-brain axis plays an important role in maintaining homeostasis. Many intrinsic and extrinsic factors influence signaling along this axis, modulating the function of both the enteric and central nervous systems. More recently the role of the microbiome as an important factor in modulating gut-brain signaling has emerged and the concept of a microbiota-gut-brain axis has been established. In this review, we highlight the role of this axis in modulating enteric and central nervous system function and how this may impact disorders such as irritable bowel syndrome and disorders of mood and affect. We examine the overlapping biological constructs that underpin these disorders with a special emphasis on the neurotransmitter serotonin, which plays a key role in both the gastrointestinal tract and in the brain. Overall, it is clear that although animal studies have shown much promise, more progress is necessary before these findings can be translated for diagnostic and therapeutic benefit in patient populations.}, }
@article {pmid33492618, year = {2021}, author = {Gonzalez, A and Kapila, N and Melendez-Rosado, J and Liang, H and Castro-Pavia, F}, title = {An Evaluation of the Fecal Microbiome in Lynch Syndrome.}, journal = {Journal of gastrointestinal cancer}, volume = {52}, number = {1}, pages = {365-368}, pmid = {33492618}, issn = {1941-6636}, mesh = {Adult ; Case-Control Studies ; Colorectal Neoplasms, Hereditary Nonpolyposis/complications/genetics/*microbiology ; DNA, Bacterial/isolation &amp; purification ; Endometrial Neoplasms/genetics/*microbiology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Male ; Mutation ; Ovarian Neoplasms/genetics/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {PURPOSE: There is limited data regarding the fecal microbiome findings in patients with Lynch syndrome. We aimed to study the fecal micobiome of patients with Lynch syndrome with and without cancer.<br><br>METHODS: We performed an observational study comparing the fecal microbiome of patients with Lynch syndrome (LS) with cancer with those without cancer. We included subjects older than 18&#xa0;years with LS and excluded those with a history of colectomy or inflammatory bowel disease. We analyzed their fecal microbiome by 16S ribosomal subunit PCR amplification and performed comparative analyses.<br><br>RESULTS: Eight patients were included: 3 of these with LS and cancer (LS-C) and 5 patients with LS and no cancer (LS-NC). We found non-significant differences at the phyla and genera level between the LS-C and LS-NC groups. At the phyla level, LS-C patients had a higher percentage of Bacteroidetes (42.2% vs. 28.5%; P&#xa0;=&#xa0;0.068) and Verrucomicrobia (0.644% vs 0.0007%; P&#xa0;=&#xa0;0.10), and a lower percentage of Firmicutes (48.3% vs. 65.4%; P&#xa0;=&#xa0;0.078). At the genus level, LS-C patients had a higher rate of Akkermania (0.766% vs. 0.001%; P&#xa0;=&#xa0;0.11). LS-C patients with endometrial cancer had a higher rate of Bacteroides (37.4% vs 17.3%; P&#xa0;=&#xa0;0.10). LS-C patients had a lower rate of Pseudobutyrvibrio (0.74% vs. 2.71%; P&#xa0;=&#xa0;0.10).<br><br>CONCLUSIONS: The fecal microbiome of LS patients with extraintestinal cancer differs that of LS patients without cancer. Further studies are needed to explore microbiome changes in these high risk patients.}, }
@article {pmid33484776, year = {2021}, author = {Horvatits, T and Wißmann, JE and Johne, R and Groschup, MH and Gadicherla, AK and Schulze Zur Wiesch, J and Eiden, M and Todt, D and Reimer, R and Dähnert, L and Schöbel, A and Horvatits, K and Lübke, R and Wolschke, C and Ayuk, F and Rybczynski, M and Lohse, AW and Addo, MM and Herker, E and Lütgehetmann, M and Steinmann, E and Pischke, S}, title = {Hepatitis E virus persists in the ejaculate of chronically infected men.}, journal = {Journal of hepatology}, volume = {75}, number = {1}, pages = {55-63}, doi = {10.1016/j.jhep.2020.12.030}, pmid = {33484776}, issn = {1600-0641}, mesh = {Animals ; Ejaculation ; Feces/*virology ; Genome, Viral ; Hematologic Tests/methods ; *Hepatitis E/blood/immunology/virology ; *Hepatitis E virus/genetics/isolation &amp; purification ; Humans ; *Immunocompetence ; Immunocompromised Host ; Male ; *Persistent Infection/immunology/virology ; Semen/*virology ; Semen Analysis/methods ; Swine ; Urinalysis/methods ; Viral Envelope ; Viral Replication Compartments ; }, abstract = {BACKGROUND &amp; AIMS: Hepatitis E virus (HEV) infections are prevalent worldwide. Various viruses have been detected in the ejaculate and can outlast the duration of viremia, indicating replication beyond the blood-testis barrier. HEV replication in diverse organs, however, is still widely misunderstood. We aimed to determine the occurrence, features and morphology of HEV in the ejaculate.<br><br>METHODS: The presence of HEV in testis was assessed in 12 experimentally HEV-genotype 3-infected pigs. We further tested ejaculate, urine, stool and blood from 3 chronically HEV genotype 3-infected patients and 6 immunocompetent patients with acute HEV infection by HEV-PCR. Morphology and genomic characterization of HEV particles from various human compartments were determined by HEV-PCR, density gradient measurement, immune-electron microscopy and genomic sequencing.<br><br>RESULTS: In 2 of the 3 chronically HEV-infected patients, we observed HEV-RNA (genotype 3c) in seminal plasma and semen with viral loads >2 logs higher than in the serum. Genomic sequencing showed significant differences between viral strains in the ejaculate compared to stool. Under ribavirin-treatment, HEV shedding in the ejaculate continued for >9 months following the end of viremia. Density gradient measurement and immune-electron microscopy characterized (enveloped) HEV particles in the ejaculate as intact.<br><br>CONCLUSIONS: The male reproductive system was shown to be a niche of HEV persistence in chronic HEV infection. Surprisingly, sequence analysis revealed distinct genetic HEV variants in the stool and serum, originating from the liver, compared to variants in the ejaculate originating from the male reproductive system. Enveloped HEV particles in the ejaculate did not morphologically differ from serum-derived HEV particles.<br><br>LAY SUMMARY: Enveloped hepatitis E virus particles could be identified by PCR and electron microscopy in the ejaculate of immunosuppressed chronically infected patients, but not in immunocompetent experimentally infected pigs or in patients with acute self-limiting hepatitis E.}, }
@article {pmid33483999, year = {2021}, author = {Marrs, T and Walter, J}, title = {Pros and cons: Is faecal microbiota transplantation a safe and efficient treatment option for gut dysbiosis?.}, journal = {Allergy}, volume = {76}, number = {7}, pages = {2312-2317}, doi = {10.1111/all.14750}, pmid = {33483999}, issn = {1398-9995}, mesh = {*Clostridium Infections/therapy ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Faecal Microbiota Transplantation (FMT) is well established as an effective treatment for Clostridioides difficile infection (CDI), restoring gut microbiome diversity and function. The utility of FMT is currently being explored in relation to other immune-mediated pathologies, such as allergic disease, inflammatory bowel diseases and autoimmune diseases. Clinical trials in these areas are ongoing, and the altered gut microbiota (dysbiosis) that is often observed in these pathologies provides a rationale for the application of FMT to restore the microbiome. However, there is controversy on the risk-benefit ratio as it relates to the use of FMTs in pathologies other than CDI. In this Pro and Con article, we present the arguments for and against the use of FMT in immune-mediated pathologies, such as allergic disease. We further identify research gaps and recommend how these may be addressed in future studies.}, }
@article {pmid33483370, year = {2021}, author = {Di Modica, M and Gargari, G and Regondi, V and Bonizzi, A and Arioli, S and Belmonte, B and De Cecco, L and Fasano, E and Bianchi, F and Bertolotti, A and Tripodo, C and Villani, L and Corsi, F and Guglielmetti, S and Balsari, A and Triulzi, T and Tagliabue, E}, title = {Gut Microbiota Condition the Therapeutic Efficacy of Trastuzumab in HER2-Positive Breast Cancer.}, journal = {Cancer research}, volume = {81}, number = {8}, pages = {2195-2206}, doi = {10.1158/0008-5472.CAN-20-1659}, pmid = {33483370}, issn = {1538-7445}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Antineoplastic Agents, Immunological/*therapeutic use ; Breast Neoplasms/*chemistry/*drug therapy/immunology ; Bridged-Ring Compounds/therapeutic use ; CD4-Positive T-Lymphocytes ; Cyclophosphamide/therapeutic use ; Cytokines/blood ; Dendritic Cells/drug effects ; Doxorubicin/therapeutic use ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/drug effects/immunology/*physiology ; Granzymes ; Humans ; Immune System ; Immunity, Mucosal ; Interferons/metabolism ; Interleukin-12/metabolism ; Mice ; Neoadjuvant Therapy ; Nitric Oxide/metabolism ; *Receptor, ErbB-2 ; Streptomycin/pharmacology ; Taxoids/therapeutic use ; Trastuzumab/*therapeutic use ; Treatment Outcome ; Tumor Microenvironment/drug effects/immunology ; Vancomycin/pharmacology ; }, abstract = {Emerging evidence indicates that gut microbiota affect the response to anticancer therapies by modulating the host immune system. In this study, we investigated the impact of gut microbiota on immune-mediated trastuzumab antitumor efficacy in preclinical models of HER2-positive breast cancer and in 24 patients with primary HER2-positive breast cancer undergoing trastuzumab-containing neoadjuvant treatment. In mice, the antitumor activity of trastuzumab was impaired by antibiotic administration or fecal microbiota transplantation from antibiotic-treated donors. Modulation of the intestinal microbiota was reflected in tumors by impaired recruitment of CD4[+] T cells and granzyme B-positive cells after trastuzumab treatment. Antibiotics caused reductions in dendritic cell (DC) activation and the release of IL12p70 upon trastuzumab treatment, a mechanism that was necessary for trastuzumab effectiveness in our model. In patients, lower α-diversity and lower abundance of Lachnospiraceae, Turicibacteraceae, Bifidobacteriaceae, and Prevotellaceae characterized nonresponsive patients (NR) compared with those who achieved pathologic complete response (R), similar to antibiotic-treated mice. The transfer of fecal microbiota from R and NR into mice bearing HER2-positive breast cancer recapitulated the response to trastuzumab observed in patients. Fecal microbiota β-diversity segregated patients according to response and positively correlated with immune signature related to interferon (IFN) and NO2-IL12 as well as activated CD4[+] T cells and activated DCs in tumors. Overall, our data reveal the direct involvement of the gut microbiota in trastuzumab efficacy, suggesting that manipulation of the gut microbiota is an optimal future strategy to achieve a therapeutic effect or to exploit its potential as a biomarker for treatment response. SIGNIFICANCE: Evidence of gut microbiota involvement in trastuzumab efficacy represents the foundation for new therapeutic strategies aimed at manipulating commensal bacteria to improve response in trastuzumab-resistant patients.See related commentary by Sharma, p. 1937 GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/8/2195/F1.large.jpg.}, }
@article {pmid33483079, year = {2021}, author = {Sang, T and Guo, C and Guo, D and Wu, J and Wang, Y and Wang, Y and Chen, J and Chen, C and Wu, K and Na, K and Li, K and Fang, L and Guo, C and Wang, X}, title = {Suppression of obesity and inflammation by polysaccharide from sporoderm-broken spore of Ganoderma lucidum via gut microbiota regulation.}, journal = {Carbohydrate polymers}, volume = {256}, number = {}, pages = {117594}, doi = {10.1016/j.carbpol.2020.117594}, pmid = {33483079}, issn = {1879-1344}, mesh = {Animals ; Body Weight ; Computational Biology ; Diet, High-Fat ; Dysbiosis ; Endotoxemia/metabolism ; Feces/microbiology ; Ganoderma/*drug effects ; *Gastrointestinal Microbiome ; Glucose Tolerance Test ; Hyperlipidemias/drug therapy/metabolism ; Inflammation/*drug therapy/metabolism ; Macrophages/cytology ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/*drug therapy/metabolism ; Polysaccharides/*chemistry ; Powders ; RNA, Ribosomal, 16S/metabolism ; Spores, Fungal ; }, abstract = {Ganoderma lucidum has been shown to have anti-obesity effects. However, polysaccharide extracted from the sporoderm-broken spores of Ganoderma lucidum (BSGLP) against obesity and its underlying mechanisms have never been reported. In the current study, we showed that BSGLP inhibited high-fat diet (HFD)-induced obesity, hyperlipidemia, inflammation, and fat accumulation in C57BL/6 J mice. BSGLP improved HFD-induced gut microbiota dysbiosis, maintained intestinal barrier function, increased short-chain fatty acids production and GPR43 expression, ameliorated endotoxemia, manifested by reduced serum lipopolysaccharide level, and increased ileum expression of tight junction proteins and antimicrobial peptides. Fecal microbiota transplantation study confirmed that BSGLP-induced microbiota change is responsible, at least in part, for obesity inhibition. Besides, BSGLP notably alleviated HFD-induced upregulation of TLR4/Myd88/NF-κB signaling pathway in adipose tissue. Collectively, our study showed for the first time that BSGLP might be used as a prebiotic agent to inhibit obesity and hyperlipidemia through modulating inflammation, gut microbiota, and gut barrier function.}, }
@article {pmid33482620, year = {2021}, author = {Nejadghaderi, SA and Nazemalhosseini-Mojarad, E and Asadzadeh Aghdaei, H}, title = {Fecal microbiota transplantation for COVID-19; a potential emerging treatment strategy.}, journal = {Medical hypotheses}, volume = {147}, number = {}, pages = {110476}, pmid = {33482620}, issn = {1532-2777}, mesh = {Bacteria/classification ; COVID-19/*therapy/virology ; China ; Cost-Benefit Analysis ; *Fecal Microbiota Transplantation ; Feces/virology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology/*virology ; Humans ; Immune System ; Lung/microbiology ; Models, Theoretical ; }, abstract = {At the end of 2019, an emerging outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first reported from Wuhan, China. The first manifestations of patients infected with SARS-CoV-2 was flu-like symptoms, while other type of manifestations, especially gastrointestinal manifestations were discovered recently. As of June 2020, there is no specific drug or treatment strategy for COVID-19, a disease caused by SARS-CoV-2, so different combination of antiviral drugs is currently being used. Gut microbiota mostly consists of four phyla, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. The interaction between gut microbiota and immune system through releasing some cytokines such as IL-1β, IL-2, IL-10, TNF-α, and IFN-γ that play roles in the severity of COVID-19. In this article, a new potential treatment for COVID-19 by fecal microbiota transplantation (FMT) is described. FMT revealed promising results in different diseases, especially recurrent clostridium difficile infection, and it might reduce length of hospital admission and severity of the disease by modification of gut microbiota composition.}, }
@article {pmid33477939, year = {2021}, author = {Burz, SD and Monnoye, M and Philippe, C and Farin, W and Ratziu, V and Strozzi, F and Paillarse, JM and Chêne, L and Blottière, HM and Gérard, P}, title = {Fecal Microbiota Transplant from Human to Mice Gives Insights into the Role of the Gut Microbiota in Non-Alcoholic Fatty Liver Disease (NAFLD).}, journal = {Microorganisms}, volume = {9}, number = {1}, pages = {}, pmid = {33477939}, issn = {2076-2607}, support = {ANR-15-CE14-0021-03//Agence Nationale de la Recherche/ ; }, abstract = {Non-alcoholic fatty liver diseases (NAFLD) are associated with changes in the composition and metabolic activities of the gut microbiota. However, the causal role played by the gut microbiota in individual susceptibility to NAFLD and particularly at its early stage is still unclear. In this context, we transplanted the microbiota from a patient with fatty liver (NAFL) and from a healthy individual to two groups of mice. We first showed that the microbiota composition in recipient mice resembled the microbiota composition of their respective human donor. Following administration of a high-fructose, high-fat diet, mice that received the human NAFL microbiota (NAFLR) gained more weight and had a higher liver triglycerides level and higher plasma LDL cholesterol than mice that received the human healthy microbiota (HR). Metabolomic analyses revealed that it was associated with lower and higher plasma levels of glycine and 3-Indolepropionic acid in NAFLR mice, respectively. Moreover, several bacterial genera and OTUs were identified as differently represented in the NAFLR and HR microbiota and therefore potentially responsible for the different phenotypes observed. Altogether, our results confirm that the gut bacteria play a role in obesity and steatosis development and that targeting the gut microbiota may be a preventive or therapeutic strategy in NAFLD management.}, }
@article {pmid33477417, year = {2021}, author = {Hassouneh, R and Bajaj, JS}, title = {Gut Microbiota Modulation and Fecal Transplantation: An Overview on Innovative Strategies for Hepatic Encephalopathy Treatment.}, journal = {Journal of clinical medicine}, volume = {10}, number = {2}, pages = {}, pmid = {33477417}, issn = {2077-0383}, support = {2I0CX001076//Office of Research and Development/ ; R21TR002024/TR/NCATS NIH HHS/United States ; R21TR003095/TR/NCATS NIH HHS/United States ; }, abstract = {Hepatic encephalopathy (HE) is a major complication of cirrhosis, which is associated with gut microbial composition and functional alterations. Current treatments largely focus on gut microbiota using lactulose, rifaximin and other agents. However, despite these treatments, patients with HE have a high rate of readmission, morbidity and cognitive impairment. Fecal microbiota transplant (FMT) involves introduction of a donor microbiota into a recipient and is currently mainly used for recurrent C. difficile infection (rCDI). The role of FMT in cirrhosis and HE is evolving. There have been two randomized clinical trials (RCT) and several case reports/series in cirrhosis. Both RCTs were safety-focused phase 1 trials. One involved pre-FMT antibiotics and FMT enema versus standard of care, while the other involved 15 FMT capsules versus placebo without pre-FMT antibiotics. There was evidence of safety in both trials and the FMT group demonstrated reduction in hospitalizations compared to the non-FMT group. Changes in microbial function centered around short-chain fatty acids, bile acids and brain function showed improvement in the FMT groups. Long-term follow-up demonstrated continued safety and reduction in the antibiotic-resistance gene carriage. However, larger trials of FMT in HE are needed that can refine the dose, duration and route of FMT administration.}, }
@article {pmid33476924, year = {2021}, author = {Wang, J and Ishfaq, M and Li, J}, title = {Lactobacillus salivarius ameliorated Mycoplasma gallisepticum-induced inflammatory injury and secondary Escherichia coli infection in chickens: Involvement of intestinal microbiota.}, journal = {Veterinary immunology and immunopathology}, volume = {233}, number = {}, pages = {110192}, doi = {10.1016/j.vetimm.2021.110192}, pmid = {33476924}, issn = {1873-2534}, mesh = {Animals ; *Chickens ; Chromatin Immunoprecipitation/veterinary ; Disease Susceptibility ; Escherichia coli Infections/etiology/microbiology/prevention &amp; control/*veterinary ; *Gastrointestinal Microbiome ; Inflammation/immunology/prevention &amp; control/veterinary ; Ligilactobacillus salivarius/*physiology ; Lung Diseases/microbiology/prevention &amp; control/veterinary ; Macrophages, Peritoneal/immunology ; Mycoplasma Infections/complications/microbiology/therapy/*veterinary ; *Mycoplasma gallisepticum ; Poultry Diseases/microbiology/*prevention &amp; control ; }, abstract = {Mycoplasma gallisepticum (MG) infection alone or in combination with other pathogens have brought huge economic losses to the poultry industry. The intestinal microbiota plays a critical role in host defence against respiratory infection. To explore the role of intestinal microbiota in MG-induced inflammation-mediated lung injury and secondary Escherichia coli infection, MG infection model and fecal microbiota transplantation model were developed. The results showed that MG infection changed gut microbiota composition along with lung inflammation injury. Fecal microbiota transplantation from chickens infected with MG to antibiotics cocktail treated chickens decreased host defense against Escherichia coli due to impaired intestinal mucosal barrier, downregulated the mRNA expression levels of host defense enzymes and blocked autophagic flux. Lactobacillus salivarius intake alleviated lung inflammation injury caused by MG infection and increased host defense against Escherichia coli by improved gut microbiota composition. These results highlighted the role of gut microbiota in MG-infection induced lung inflammation injury and secondary infection that offered a new strategy for preventive intervention against MG infection.}, }
@article {pmid33476379, year = {2021}, author = {Rupawala, AH and Gachette, D and Bakhit, M and Jimoh, L and Kelly, CR}, title = {Management of Severe and Severe/Complicated Clostridoides difficile Infection Using Sequential Fecal Microbiota Transplant by Retention Enema.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {73}, number = {4}, pages = {716-719}, doi = {10.1093/cid/ciab041}, pmid = {33476379}, issn = {1537-6591}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; Enema ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {We evaluated serial fecal microbiota transplant (FMT) by retention enema in patients with severe or severe/complicated Clostridoides difficile infection (CDI) unresponsive to at least 48 hours of standard antibiotic therapy. Of the 15 patients included, despite initial improvement in most patients, only 5 patients sustained cure at 30 days, and serious adverse events occurred in 4 patients.}, }
@article {pmid33475201, year = {2021}, author = {Kou, G and Li, P and Hu, Y and Chen, H and Nyantakyiwaa Amoah, A and Seydou Traore, S and Cui, Z and Lyu, Q}, title = {Nobiletin activates thermogenesis of brown and white adipose tissue in high-fat diet-fed C57BL/6 mice by shaping the gut microbiota.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {2}, pages = {e21267}, doi = {10.1096/fj.202002197R}, pmid = {33475201}, issn = {1530-6860}, mesh = {Acetates/metabolism ; Adipose Tissue, Brown/*drug effects/metabolism ; Adipose Tissue, White/*drug effects/metabolism ; Animals ; Antioxidants/administration &amp; dosage/*pharmacology/therapeutic use ; Diet, High-Fat/adverse effects ; Flavones/administration &amp; dosage/*pharmacology/therapeutic use ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/*drug therapy/etiology/prevention &amp; control ; *Thermogenesis ; }, abstract = {Increasing energy expenditure by activating thermogenesis in brown and beige adipocytes is a critical approach to protect against obesity. Here, we investigated the action and mechanism of a natural polymethoxyflavone on adaptive thermogenesis in high-fat diet-induced obesity mouse model. Nobiletin treatment significantly ameliorated obesity, alleviated the whitening of brown adipose tissue, and promoted browning of white adipose tissue in mice fed a high-fat diet. Gut microbiota analysis and metabolomic profiling revealed that nobiletin treatment resulted in a composition shift in the gut microbiota thereby altering fermentation products acetate levels in the host feces and serum. Further, transplantation of the microbiota from nobiletin-treated mice to microbiota-depleted mice activated brown adipose tissue activity, promoted beige adipocytes formation, and improved high-fat diet-induced obesity. Our results indicate that nobiletin could be used as a dietary therapy to prevent HFD-induced obesity, and provide a potential target-specific gut microbial species-driven mechanism for activating thermogenesis in brown and beige adipocytes.}, }
@article {pmid33472193, year = {2020}, author = {Aburahma, A and Pachhain, S and Choudhury, SR and Rana, S and Phuntumart, V and Larsen, R and Sprague, JE}, title = {Potential Contribution of the Intestinal Microbiome to Phenethylamine-Induced Hyperthermia.}, journal = {Brain, behavior and evolution}, volume = {95}, number = {5}, pages = {256-271}, doi = {10.1159/000512098}, pmid = {33472193}, issn = {1421-9743}, mesh = {Animals ; *Gastrointestinal Microbiome ; Hyperthermia ; Phenethylamines ; Rats ; Thermogenesis ; }, abstract = {Phenethylamines (e.g., methamphetamine) are a common source of drug toxicity. Phenethylamine-induced hyperthermia (PIH) can activate a cascade of events that may result in rhabdomyolysis, coagulopathy, and even death. Here, we review recent evidence that suggests a potential link between the gut-brain axis and PIH. Within the preoptic area of the hypothalamus, phenethylamines lead to changes in catecholamine levels, that activate the sympathetic nervous system (SNS) and increase the peripheral levels of norepinephrine (NE), resulting in: (1) the loss of heat dissipation through α1 adrenergic receptor (α1-AR)-mediated vasoconstriction, (2) heat generation through β-AR activation and subsequent free fatty acid (FFA) activation of uncoupling proteins (UCPs) in brown and white adipose tissue, and (3) alteration of the gut microbiome and its link to the gut-brain axis. Recent studies have shown that phenethylamine derivatives can influence the composition of the gut microbiome and thus its metabolic potential. Phenethylamines increase the relative level of Proteuswhich has been linked to enhanced NE turnover. Bidirectional fecal microbial transplants (FMT) between PIH-tolerant and PIH-naïve rats demonstrated that the transplantation of gut microbiome can confer phenotypic hyperthermic and tolerant responses to phenethylamines. These phenethylamine-mediated changes in the gut microbiome were also associated with epigenetic changes in the mediators of thermogenesis. Given the significant role that the microbiome has been shown to play in the maintenance of body temperature, we outline current studies demonstrating the effects of phenethylamines on the gut microbiome and how these microbiome changes may mechanistically contribute to alterations in body temperature.}, }
@article {pmid33471490, year = {2021}, author = {Du, C and Luo, Y and Walsh, S and Grinspan, A}, title = {Oral Fecal Microbiota Transplant Capsules Are Safe and Effective for Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical gastroenterology}, volume = {55}, number = {4}, pages = {300-308}, pmid = {33471490}, issn = {1539-2031}, mesh = {Capsules ; Clostridioides ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Neoplasm Recurrence, Local ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome ; }, abstract = {GOALS: We performed a systematic review with meta-analysis to examine the efficacy and safety of oral fecal microbiota transplantation (FMT) capsules for recurrent Clostridioides difficile infection (rCDI).<br><br>BACKGROUND: FMT through colonoscopy is established as effective and safe in treating multiple recurrences of CDI, but consensus has not been established on delivery through oral capsules.<br><br>STUDY: A systematic literature search was performed with multiple databases including MEDLINE and EMBASE to identify original studies including at least 10 patients that investigated the role of oral FMT capsules to treat rCDI. Cure rates were pooled by a random effects model and publication bias was assessed with the Egger test. Secondary analyses assessed for differences between capsule preparation (frozen vs. lyophilized stool) and delivery modality (capsule vs. colonoscopy).<br><br>RESULTS: Fifteen studies (12 case series and 3 randomized controlled trials) encompassing 763 patients were identified for inclusion. Significant variability existed in baseline patient characteristics and protocols. Meta-analysis of proportions showed efficacy of oral FMT capsules to be 0.821 (95% confidence interval: 0.762-0.874). No evidence for publication bias was found (P=0.51). Secondary analyses did not find significant differences in efficacy. Fourteen adverse events leading to death or hospitalization were noted, none of which were attributed to FMT.<br><br>CONCLUSIONS: Oral FMT capsules for rCDI are promising because of ease of administration and noninvasive delivery. We found an overall efficacy of 82.1% with a low rate of serious adverse events. Further studies are needed to optimize protocols and outcomes.}, }
@article {pmid33470649, year = {2021}, author = {Wu, X and Cui, BT and Zhang, FM}, title = {Washed microbiota transplantation for the treatment of recurrent fungal infection in a patient with ulcerative colitis.}, journal = {Chinese medical journal}, volume = {134}, number = {6}, pages = {741-742}, pmid = {33470649}, issn = {2542-5641}, mesh = {*Colitis, Ulcerative/therapy ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Mycoses ; Treatment Outcome ; }, }
@article {pmid33468689, year = {2021}, author = {Simsek, C and Corman, VM and Everling, HU and Lukashev, AN and Rasche, A and Maganga, GD and Binger, T and Jansen, D and Beller, L and Deboutte, W and Gloza-Rausch, F and Seebens-Hoyer, A and Yordanov, S and Sylverken, A and Oppong, S and Sarkodie, YA and Vallo, P and Leroy, EM and Bourgarel, M and Yinda, KC and Van Ranst, M and Drosten, C and Drexler, JF and Matthijnssens, J}, title = {At Least Seven Distinct Rotavirus Genotype Constellations in Bats with Evidence of Reassortment and Zoonotic Transmissions.}, journal = {mBio}, volume = {12}, number = {1}, pages = {}, pmid = {33468689}, issn = {2150-7511}, mesh = {Animals ; COVID-19/transmission/virology ; Chiroptera/*virology ; Diarrhea/virology ; Genetic Variation ; Genome, Viral ; Genotype ; Horses ; Humans ; Metagenomics ; Middle East Respiratory Syndrome Coronavirus/isolation &amp; purification ; Phylogeny ; Rotavirus/*genetics ; Rotavirus Infections/*transmission/*virology ; SARS-CoV-2/isolation &amp; purification ; Zoonoses/*transmission/*virology ; }, abstract = {Bats host many viruses pathogenic to humans, and increasing evidence suggests that rotavirus A (RVA) also belongs to this list. Rotaviruses cause diarrheal disease in many mammals and birds, and their segmented genomes allow them to reassort and increase their genetic diversity. Eighteen out of 2,142 bat fecal samples (0.8%) collected from Europe, Central America, and Africa were PCR-positive for RVA, and 11 of those were fully characterized using viral metagenomics. Upon contrasting their genomes with publicly available data, at least 7 distinct bat RVA genotype constellations (GCs) were identified, which included evidence of reassortments and 6 novel genotypes. Some of these constellations are spread across the world, whereas others appear to be geographically restricted. Our analyses also suggest that several unusual human and equine RVA strains might be of bat RVA origin, based on their phylogenetic clustering, despite various levels of nucleotide sequence identities between them. Although SA11 is one of the most widely used reference strains for RVA research and forms the backbone of a reverse genetics system, its origin remained enigmatic. Remarkably, the majority of the genotypes of SA11-like strains were shared with Gabonese bat RVAs, suggesting a potential common origin. Overall, our findings suggest an underexplored genetic diversity of RVAs in bats, which is likely only the tip of the iceberg. Increasing contact between humans and bat wildlife will further increase the zoonosis risk, which warrants closer attention to these viruses.IMPORTANCE The increased research on bat coronaviruses after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) allowed the very rapid identification of SARS-CoV-2. This is an excellent example of the importance of knowing viruses harbored by wildlife in general, and bats in particular, for global preparedness against emerging viral pathogens. The current effort to characterize bat rotavirus strains from 3 continents sheds light on the vast genetic diversity of rotaviruses and also hints at a bat origin for several atypical rotaviruses in humans and animals, implying that zoonoses of bat rotaviruses might occur more frequently than currently realized.}, }
@article {pmid33468234, year = {2021}, author = {Toresson, L and Steiner, JM and Suchodolski, JS}, title = {Cholestyramine treatment in two dogs with presumptive bile acid diarrhoea: a case report.}, journal = {Canine medicine and genetics}, volume = {8}, number = {1}, pages = {1}, pmid = {33468234}, issn = {2662-9380}, abstract = {BACKGROUND: In people, bile acid diarrhoea is a prevalent complication of Crohn's disease and diarrhoea-associated irritable bowel syndrome. Affected patients typically respond to bile acid sequestrants, such as cholestyramine, but human gastroenterologists often fail to recognize bile acid diarrhoea. Consequently, bile acid diarrhoea is regarded as an underrecognized and undertreated condition in human medicine. Due to lack of diagnostic tools, clinical response to bile acid sequestrants is often used to confirm a diagnosis of bile acid diarrhoea in people. Several recent studies have shown that bile acid dysmetabolism also occurs in dogs with chronic enteropathies. It has further been shown that dogs with chronic enteropathies have significantly decreased expression of a bile acid transport protein in the ileum compared to healthy dogs, which correlates with faecal bile acid dysmetabolism. Consequently, in spite of the lack of reports in the literature, bile acid diarrhoea is likely to exist in dogs as well.<br><br>CASE DESCRIPTIONS: Two dogs, an 8-year old Rottweiler and a 4.5-year old Siberian Husky were evaluated for chronic watery diarrhoea. Neither dog responded to dietary trials, probiotics, cyclosporine, faecal microbial transplantations or metronidazole. One of the dogs responded to high daily doses of corticosteroids, which were however associated with unacceptable side effects. The other dog was refractory to all standard treatment protocols, including cyclosporine and corticosteroids. Since none of the dogs responded satisfactorily to standard treatment or modulation of the intestinal microbiome, a suspicion of possible bile acid diarrhoea was raised. Treatment with cholestyramine, a bile acid sequestrant was initiated and resulted in marked improvement of faecal consistency, frequency of defecation and activity level in both dogs.<br><br>CONCLUSION: This report presents two dogs with presumed bile acid diarrhoea that were successfully treated with cholestyramine. Therefore, bile acid diarrhoea should be considered as a possible diagnosis in dogs with treatment-refractory chronic diarrhoea.}, }
@article {pmid33468164, year = {2021}, author = {Fang, H and Fu, L and Li, X and Lu, C and Su, Y and Xiong, K and Zhang, L}, title = {Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {18}, pmid = {33468164}, issn = {1475-2859}, support = {No. 1408085MH178//Natural Science Foundation of Anhui Province/ ; }, mesh = {Adult ; Colitis, Ulcerative/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Middle Aged ; Pilot Projects ; Prospective Studies ; Recurrence ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC).<br><br>RESULTS: Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were&#xa0;randomized to the FMT group (n&#x2009;=&#x2009;10) and the control group (n&#x2009;=&#x2009;10); 80% were females (F/M&#x2009;=&#x2009;16/4), the mean age was 48&#x2009;&#xb1;&#x2009;14&#xa0;years, and the mean duration was 6.4&#x2009;&#xb1;&#x2009;8.2&#xa0;years. The mean length of post-FMT follow-up was 19.1&#x2009;&#xb1;&#x2009;10.1&#xa0;months (6-38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n&#x2009;=&#x2009;10) when reassessed at week 4 (P&#x2009;=&#x2009;0.001) and week 8 (P&#x2009;=&#x2009;0.019) after FMT; there was no significant difference 6&#xa0;months after treatment. The median remission time was 24&#xa0;months (95% CI 68.26-131.7%) in both the FMT (range 6-38&#xa0;months) and control groups (range 7-35&#xa0;months), with no significant difference (P&#x2009;=&#x2009;0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2&#xa0;weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation.<br><br>CONCLUSIONS: Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recurrent UC or even primary UC.}, }
@article {pmid33466665, year = {2021}, author = {De Santis, S and Liso, M and Vacca, M and Verna, G and Cavalcanti, E and Coletta, S and Calabrese, FM and Eri, R and Lippolis, A and Armentano, R and Mastronardi, M and De Angelis, M and Chieppa, M}, title = {Dysbiosis Triggers ACF Development in Genetically Predisposed Subjects.}, journal = {Cancers}, volume = {13}, number = {2}, pages = {}, pmid = {33466665}, issn = {2072-6694}, support = {PON - Ricerca e Innovazione 2014-2020 - Progetto AIM1801289 - attivit&#xe0; 3 - linea 1//Regione Puglia/ ; PON "2014-2020 E FSC - C.P. ARS01_01220" - BIOMIS//Regione Puglia/ ; Ricerca Corrente 2019//Ministero della Salute/ ; 5x1000//M.I.Cro./ ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide, characterized by a multifactorial etiology including genetics, lifestyle, and environmental factors including microbiota composition. To address the role of microbial modulation in CRC, we used our recently established mouse model (the Winnie-APC[Min/+]) combining inflammation and genetics.<br><br>METHODS: Gut microbiota profiling was performed on 8-week-old Winnie-APC[Min/+] mice and their littermates by 16S rDNA gene amplicon sequencing. Moreover, to study the impact of dysbiosis induced by the mother's genetics in ACF development, the large intestines of APC[Min/+] mice born from wild type mice were investigated by histological analysis at 8 weeks.<br><br>RESULTS: ACF development in 8-week-old Winnie-APC[Min/+] mice was triggered by dysbiosis. Specifically, the onset of ACF in genetically predisposed mice may result from dysbiotic signatures in the gastrointestinal tract of the breeders. Additionally, fecal transplant from Winnie donors to APC[Min/+] hosts leads to an increased rate of ACF development.<br><br>CONCLUSIONS: The characterization of microbiota profiling supporting CRC development in genetically predisposed mice could help to design therapeutic strategies to prevent dysbiosis. The application of these strategies in mothers during pregnancy and lactation could also reduce the CRC risk in the offspring.}, }
@article {pmid33463536, year = {2021}, author = {Bao, R and Hesser, LA and He, Z and Zhou, X and Nadeau, KC and Nagler, CR}, title = {Fecal microbiome and metabolome differ in healthy and food-allergic twins.}, journal = {The Journal of clinical investigation}, volume = {131}, number = {2}, pages = {}, pmid = {33463536}, issn = {1558-8238}, support = {R01 AI140134/AI/NIAID NIH HHS/United States ; R01 AI146099/AI/NIAID NIH HHS/United States ; R01 HL118612/HL/NHLBI NIH HHS/United States ; R56 AI134923/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/*classification/genetics/growth &amp; development ; Child ; Child, Preschool ; Feces/*microbiology ; Female ; Food Hypersensitivity/*microbiology ; Humans ; Infant ; Male ; *Microbiota ; Middle Aged ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; *Twins ; }, abstract = {BACKGROUNDThere has been a striking generational increase in the prevalence of food allergies. We have proposed that this increase can be explained, in part, by alterations in the commensal microbiome.METHODSTo identify bacterial signatures and metabolic pathways that may influence the expression of this disease, we collected fecal samples from a unique, well-controlled cohort of twins concordant or discordant for food allergy. Samples were analyzed by integrating 16S rRNA gene amplicon sequencing and liquid chromatography-tandem mass spectrometry metabolite profiling.RESULTSA bacterial signature of 64 operational taxonomic units (OTUs) distinguished healthy from allergic twins; the OTUs enriched in the healthy twins were largely taxa from the Clostridia class. We detected significant enrichment in distinct metabolite pathways in each group. The enrichment of diacylglycerol in healthy twins is of particular interest for its potential as a readily measurable fecal biomarker of health. In addition, an integrated microbial-metabolomic analysis identified a significant association between healthy twins and Phascolarctobacterium faecium and Ruminococcus bromii, suggesting new possibilities for the development of live microbiome-modulating biotherapeutics.CONCLUSIONTwin pairs exhibited significant differences in their fecal microbiomes and metabolomes through adulthood, suggesting that the gut microbiota may play a protective role in patients with food allergies beyond the infant stage.TRIAL REGISTRATIONParticipants in this study were recruited as part of an observational study (ClinicalTrials.gov NCT01613885) at multiple sites from 2014 to 2018.FUNDINGThis work was supported by the Sunshine Charitable Foundation; the Moss Family Foundation; the National Institute of Allergy and Infectious Diseases (NIAID) (R56AI134923 and R01AI 140134); the Sean N. Parker Center for Allergy and Asthma Research; the National Heart, Lung, and Blood Institute (R01 HL 118612); the Orsak family; the Kepner family; and the Stanford Institute for Immunity, Transplant and Infection.}, }
@article {pmid33462586, year = {2021}, author = {McGill, SK}, title = {Fecal Microbiota Transplant for Severe Clostridioides Difficile Infection: Let's Halt the Raging Fire.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {73}, number = {4}, pages = {720-721}, doi = {10.1093/cid/ciab047}, pmid = {33462586}, issn = {1537-6591}, mesh = {Clostridioides ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid33459581, year = {2021}, author = {Lee, MW and Yeon, SH and Heo, BY and Kwon, J and Ryu, H and Lee, HJ and Yun, HJ and Jo, DY and Song, IC}, title = {Impact of pre-transplant use of antibiotics on the graft-versus-host disease in adult patients with hematological malignancies.}, journal = {Hematology (Amsterdam, Netherlands)}, volume = {26}, number = {1}, pages = {96-102}, doi = {10.1080/16078454.2021.1872957}, pmid = {33459581}, issn = {1607-8454}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Carbapenems/therapeutic use ; Cefepime/therapeutic use ; Disease-Free Survival ; Female ; Glycopeptides/therapeutic use ; Graft vs Host Disease/etiology/*prevention &amp; control ; Hematologic Neoplasms/*therapy ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Humans ; Immunosuppressive Agents/therapeutic use ; Male ; Methotrexate/therapeutic use ; Middle Aged ; Piperacillin, Tazobactam Drug Combination/therapeutic use ; Retrospective Studies ; Transplantation, Homologous/adverse effects/methods ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVES: Changes in fecal microbiota affect the incidence and extent of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Most patients with hematological malignancies receive antibiotics for the treatment of febrile neutropenia prior to allogeneic HSCT, and pre-transplant use of antibiotics may influence the fecal microbiota and GVHD.<br><br>METHODS: We retrospectively analysed consecutive adult patients with hematological malignancies who received allogeneic HSCT at Chungnam National University Hospital between 2007 and 2018. Pre-transplant use of antibiotics was defined as the use of antibiotics before conditioning chemotherapy.<br><br>RESULTS: This study included 131 patients with a median age of 46 (range, 18-71) years: 76 (58%) patients were AML, 28 (21.4%) with ALL, 23 (17.6%) with MDS, and 4 (3.1%) with CML. All patients received calcineurin inhibitors with short-course methotrexate for GVHD prophylaxis. A total of 31 (23.7%) patients received anti-thymocyte globulin. All patients received antibiotics prior to HSCT: 70 (53.4%) patients received glycopeptide, 114 (87.0%) received cefepime, 87 (66.4%) received piperacillin/tazobactam, and 51 (38.9%) received carbapenem. Patients who received glycopeptide had more frequently extensive chronic GVHD (cGVHD) than those who did not (51.1% vs. 28.1% at 5 years) and had more frequently cGVHD of the lung (34.8% vs. 15.8% at 5 years). Pre-transplant use of glycopeptide did not affect the overall survival (OS) or GVHD- and relapse-free survival (GRFS) (median OS; 49 months in glycopeptide group vs. not reached in non-glycopeptide group, p=0.475; median GRFS; 9 months in glycopeptide group vs. 16 months in non-glycopeptide group, p=0.092).<br><br>CONCLUSION: Pre-transplant use of glycopeptide tends to increase the incidence of extensive cGVHD.}, }
@article {pmid33452411, year = {2021}, author = {Liu, Y and Fan, L and Cheng, Z and Yu, L and Cong, S and Hu, Y and Zhu, L and Zhang, B and Cheng, Y and Zhao, P and Zhao, X and Cheng, M}, title = {Fecal transplantation alleviates acute liver injury in mice through regulating Treg/Th17 cytokines balance.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {1611}, pmid = {33452411}, issn = {2045-2322}, mesh = {Animals ; Bilirubin/blood ; Chemical and Drug Induced Liver Injury/metabolism/*pathology ; Cytokines/*metabolism ; Disease Models, Animal ; Down-Regulation ; *Fecal Microbiota Transplantation ; Galactosamine/toxicity ; Gastrointestinal Microbiome ; Interleukin-10/metabolism ; Interleukin-17/metabolism ; Liver Function Tests ; Male ; Mice ; Mice, Inbred BALB C ; Principal Component Analysis ; Saccharomyces boulardii/physiology ; T-Lymphocytes, Regulatory/cytology/immunology/*metabolism ; Th17 Cells/cytology/immunology/*metabolism ; Up-Regulation ; }, abstract = {Changes in intestinal microecology during acute liver failure (ALF) directly affect the occurrence and development of the disease. The study aimed to investigate the relationship between the intestinal microbiota and the key immune cells. Fecal microbiota transplantation (FMT) was used to determine whether ALF can balance Th17/Treg cytokines. The relationship between gut microbiota and clinical indicators was analyzed. BALB/c mice were treated with D-galactosamine (D-GalN) to induce a murine ALF model. FMT to D-GalN mice was conducted to test for liver function indicators. Results showed that the proportions of Lachnospiraceae, Prevotella, S24-7, Odoribacter and Rikenellaceae in D-GalN mice with intestinal microbiota disorder were restored after FMT. Further, CIA analysis showed that bacteria had a covariant relationship with clinical indicators. Microbiota could account for changes in 49.9% of the overall clinical indicators. Adonis analysis showed that Ruminococcus, and Enterococcus have a greater impact on clinical indicators. FMT down-regulated the expression of IL-17A, TNF-α, and TGF-β, while up-regulated IL-10 and IL-22. Transplantation of feces from Saccharomyces boulardii donor mice improved GalN-induced liver damage. These findings indicate that FMT attenuates D-GalN-induced liver damage in mice, and a clinical trial is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with ALF.}, }
@article {pmid33444574, year = {2021}, author = {Cook, L and Rees, WD and Wong, MQ and Peters, H and Levings, MK and Steiner, TS}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection Enhances Adaptive Immunity to C difficile Toxin B.}, journal = {Gastroenterology}, volume = {160}, number = {6}, pages = {2155-2158.e4}, doi = {10.1053/j.gastro.2021.01.009}, pmid = {33444574}, issn = {1528-0012}, support = {20R76508//CIHR/Canada ; 20R75988//CIHR/Canada ; }, mesh = {*Adaptive Immunity ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacterial Proteins/*immunology ; Bacterial Toxins/*immunology ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Enterotoxins/immunology ; *Fecal Microbiota Transplantation ; Female ; Humans ; Immunoglobulin A/blood ; Immunoglobulin G/blood ; Interleukin-17/metabolism ; Interleukins/metabolism ; Male ; Middle Aged ; Receptors, Antigen, T-Cell/metabolism ; Recurrence ; *Th17 Cells/metabolism ; Th2 Cells ; Young Adult ; Interleukin-22 ; }, }
@article {pmid33444573, year = {2021}, author = {Saha, S and Mara, K and Pardi, DS and Khanna, S}, title = {Long-term Safety of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Gastroenterology}, volume = {160}, number = {6}, pages = {1961-1969.e3}, doi = {10.1053/j.gastro.2021.01.010}, pmid = {33444573}, issn = {1528-0012}, support = {UL1 TR002377/TR/NCATS NIH HHS/United States ; U01 FD005938/FD/FDA HHS/United States ; UL1 TR000135/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; Constipation/*etiology ; Diabetes Mellitus/epidemiology ; Diarrhea/*etiology ; Dyslipidemias/epidemiology ; Enterocolitis, Pseudomembranous/complications/drug therapy/*therapy ; Fecal Microbiota Transplantation/*adverse effects/statistics &amp; numerical data ; Female ; Humans ; Inflammatory Bowel Diseases/complications/epidemiology ; Male ; Middle Aged ; Pneumonia/epidemiology ; Prospective Studies ; Recurrence ; Risk Factors ; Sepsis/epidemiology ; Surveys and Questionnaires ; Time Factors ; Urinary Tract Infections/epidemiology ; Weight Gain ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI), with emerging data on intermediate and long-term safety.<br><br>METHODS: A prospective survey-based study was conducted (September 2012-June 2018) in patients undergoing FMT for recurrent CDI. Data on demographics and comorbidities were abstracted from medical records. Patients were contacted at 1 week, 1 month, 6 months, 1 year (short-term), and &#x2265;2 years post-FMT (long-term). Symptoms and new medical diagnoses were recorded at each time point. Data were weighted to account for survey nonresponse bias. Multivariate logistic regression models for adverse events were built using age (per 10-year increment), sex, time of survey, and comorbidities. P < .05 was considered statistically significant.<br><br>RESULTS: Overall, 609 patients underwent FMT; median age was 56 years (range, 18-94), 64.8% were women, 22.8% had inflammatory bowel disease (IBD). At short-term follow-up (n&#xa0;= 609), >60% of patients had diarrhea and 19%-33% had constipation. At 1 year, 9.5% reported additional CDI episodes. On multivariable analysis, patients with IBD, dialysis-dependent kidney disease, and multiple FMTs had higher risk of diarrhea; risk of constipation was higher in women and lower in IBD (all P < .05). For long-term follow-up (n&#xa0;= 447), median time of follow-up was 3.7 years (range, 2.0-6.8). Overall, 73 new diagnoses were reported: 13% gastrointestinal, 10% weight gain, 11.8% new infections (all deemed unrelated to FMT). Median time to infections was 29 months (range, 0-73) post-FMT.<br><br>CONCLUSION: FMT appears safe with low risk of transmission of infections. Several new diagnoses were reported, which should be explored in future studies.}, }
@article {pmid33444319, year = {2021}, author = {McKinney, CA and Bedenice, D and Pacheco, AP and Oliveira, BCM and Paradis, MR and Mazan, M and Widmer, G}, title = {Assessment of clinical and microbiota responses to fecal microbial transplantation in adult horses with diarrhea.}, journal = {PloS one}, volume = {16}, number = {1}, pages = {e0244381}, pmid = {33444319}, issn = {1932-6203}, support = {R21 AI125891/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Case-Control Studies ; Colitis/therapy ; Diarrhea/pathology/*therapy ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Horses ; *Microbiota ; Principal Component Analysis ; Severity of Illness Index ; }, abstract = {BACKGROUND AND AIMS: Fecal microbial transplantation (FMT) is empirically implemented in horses with colitis to facilitate resolution of diarrhea. The purpose of this study was to assess FMT as a clinical treatment and modulator of fecal microbiota in hospitalized horses with colitis.<br><br>METHODS: A total of 22 horses with moderate to severe diarrhea, consistent with a diagnosis of colitis, were enrolled at two referral hospitals (L1: n = 12; L2: n = 10). FMT was performed in all 12 patients on 3 consecutive days at L1, while treatment at L2 consisted of standard care without FMT. Manure was collected once daily for 4 days from the rectum in all colitis horses, prior to FMT for horses at L1, and from each manure sample used for FMT. Fecal samples from 10 clinically healthy control horses housed at L2, and 30 healthy horses located at 5 barns in regional proximity to L1 were also obtained to characterize the regional healthy equine microbiome. All fecal microbiota were analyzed using 16S amplicon sequencing.<br><br>RESULTS AND CONCLUSIONS: As expected, healthy horses at both locations showed a greater &#x3b1;-diversity and lower &#x3b2;-diversity compared to horses with colitis. The fecal microbiome of healthy horses clustered by location, with L1 horses showing a higher prevalence of Kiritimatiellaeota. Improved manure consistency (lower diarrhea score) was associated with a greater &#x3b1;-diversity in horses with colitis at both locations (L1: r = -0.385, P = 0.006; L2: r = -0.479, P = 0.002). Fecal transplant recipients demonstrated a greater overall reduction in diarrhea score (median: 4&#xb1;3 grades), compared to untreated horses (median: 1.5&#xb1;3 grades, P = 0.021), with a higher incidence in day-over-day improvement in diarrhea (22/36 (61%) vs. 10/28 (36%) instances, P = 0.011). When comparing microbiota of diseased horses at study conclusion to that of healthy controls, FMT-treated horses showed a lower mean UniFrac distance (0.53&#xb1;0.27) than untreated horses (0.62&#xb1;0.26, P<0.001), indicating greater normalization of the microbiome in FMT-treated patients.}, }
@article {pmid33443235, year = {2021}, author = {Cho, YS}, title = {Fecal Microbiota Transplantation Is Effective for the Treatment of Partially Treated Clostridioides difficile Infection.}, journal = {Gut and liver}, volume = {15}, number = {1}, pages = {1-2}, pmid = {33443235}, issn = {2005-1212}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid33443023, year = {2021}, author = {Zhang, C and Xiong, B and Chen, L and Ge, W and Yin, S and Feng, Y and Sun, Z and Sun, Q and Zhao, Y and Shen, W and Zhang, H}, title = {Rescue of male fertility following faecal microbiota transplantation from alginate oligosaccharide-dosed mice.}, journal = {Gut}, volume = {70}, number = {11}, pages = {2213-2215}, pmid = {33443023}, issn = {1468-3288}, mesh = {Alginates ; Animals ; *Fecal Microbiota Transplantation ; Fertility ; *Gastrointestinal Microbiome ; Male ; Mice ; Oligosaccharides ; }, }
@article {pmid33442010, year = {2021}, author = {Stower, H}, title = {Microbiome transplant-induced response to immunotherapy.}, journal = {Nature medicine}, volume = {27}, number = {1}, pages = {21}, doi = {10.1038/s41591-020-01220-6}, pmid = {33442010}, issn = {1546-170X}, mesh = {Fecal Microbiota Transplantation ; Humans ; Immunotherapy ; *Melanoma ; *Microbiota ; }, }
@article {pmid33441186, year = {2021}, author = {Yoshimatsu, Y and Mikami, Y and Kanai, T}, title = {Bacteriotherapy for inflammatory bowel disease.}, journal = {Inflammation and regeneration}, volume = {41}, number = {1}, pages = {3}, pmid = {33441186}, issn = {1880-9693}, support = {16gm1010003h0001//Japan Agency for Medical Research and Development/ ; 20gm1210001h0002//Japan Agency for Medical Research and Development/ ; NA//the Takeda Science Foundation/ ; NA//the Kanae Foundation for The Promotion of Medical Science/ ; 20H03666//Japan Society for the Promotion of Science/ ; 15H02534//Japan Society for the Promotion of Science/ ; 20H00536//Japan Society for the Promotion of Science/ ; NA//Mishima Kaiun Memorial Foundation/ ; NA//School of Medicine, Keio University/ ; }, abstract = {The number of patients with inflammatory bowel disease is rapidly increasing in developed countries. The main cause of this increase is thought not to be genetic, but secondary to rapidly modernized environmental change. Changes in the environment have been detrimental to enteric probiotics useful for fermentation, inducing an increase in pathobionts that survive by means other than fermentation. This dysregulated microbiota composition, the so-called dysbiosis, is believed to have increased the incidence of inflammatory bowel disease. Bacteriotherapy, a treatment that prophylactically and therapeutically corrects the composition of disturbed intestinal microbiota, is a promising recent development. In fact, fecal microbiome transplantation for recurrent Clostridioides difficile infection in 2013 was a significant contribution for bacteriotherapy. In this paper, we comprehensively review bacteriotherapy in an easy-to-understand format.}, }
@article {pmid33439534, year = {2020}, author = {Zhao, HL and Chen, SZ and Xu, HM and Zhou, YL and He, J and Huang, HL and Xu, J and Nie, YQ}, title = {Efficacy and safety of fecal microbiota transplantation for treating patients with ulcerative colitis: A systematic review and meta-analysis.}, journal = {Journal of digestive diseases}, volume = {21}, number = {10}, pages = {534-548}, doi = {10.1111/1751-2980.12933}, pmid = {33439534}, issn = {1751-2980}, support = {//National Natural Science Foundation of China, Grant/Award Numbers: 81700487, 81871905; Guangdong Medical Science and Technology Research Fund, Grant/Award Number: A2019243; Fundamental Research Funds for the Central Universities, South China University of Technology, Grant/Award Number: 2018MS82; Guangzhou Planned Project of Science and Technology, Grant/Award Number: 202002030288; Innovative Clinical Technique of Guangzhou, Grant/Award Number: 2019GX05./ ; }, mesh = {*Colitis, Ulcerative/therapy ; Controlled Clinical Trials as Topic ; *Fecal Microbiota Transplantation ; Humans ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {OBJECTIVES: To assess the effect of donor selection, stool procedures and pretreatment with antibiotics on the efficacy and safety of fecal microbiota transplantation (FMT)-treated ulcerative colitis (UC).<br><br>METHODS: A systematic review and meta-analysis was conducted including studies on UC treated with FMT as the primary therapeutic agent published up to June 30, 2020. Primary end-point data included clinical remission (CR) or CR combined with endoscopic remission.<br><br>RESULTS: A total of 37 studies (seven random controlled trials [RCTs], five controlled and 25 uncontrolled cohort studies) and 959 patients with UC were enrolled. In controlled cohort studies and RCTs, FMT had a significantly greater benefit than placebo (pooled odds ratio [P-OR] 3.392, 95% CI 2.196-5.240, P&#x2009;<&#x2009;0.001), with no heterogeneity (I[2] =&#x2009;0%). Furthermore, administration of FMT via the lower gastrointestinal (GI) tract was more effective in achieving CR than via the upper GI tract (44.3% vs 31.7%). The remission rate was also higher when the total stool dosage was over 275&#x2009;g compared with less than 275&#x2009;g (51.9% vs 29.5%). Overall, the incidence of serious adverse events of FMT was 5.9%. There was no significant difference between single and multiple donors, fresh and frozen stool sample used, and whether or not antibiotic pretreatment was administered before FMT.<br><br>CONCLUSION: FMT administration via the lower GI tract and using higher dosage appear to be effective and safe in inducing remission of active UC.}, }
@article {pmid33439367, year = {2021}, author = {Hammeken, LH and Baunwall, SMD and Hvas, CL and Ehlers, LH}, title = {Health economic evaluations comparing faecal microbiota transplantation with antibiotics for treatment of recurrent Clostridioides difficile infection: a systematic review.}, journal = {Health economics review}, volume = {11}, number = {1}, pages = {3}, pmid = {33439367}, issn = {2191-1991}, support = {8056-00006B//Innovationsfonden/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is increasingly being used in the treatment of recurrent Clostridioides difficile infection (rCDI). Health economic evaluations may support decision-making regarding the implementation of FMT in clinical practice. Previous reviews have highlighted several methodological concerns in published health economic evaluations examining FMT. However, the impact of these concerns on the conclusions of the studies remains unclear.<br><br>AIMS: To present an overview and assess the methodological quality of health economic evaluations that compare FMT with antibiotics for treatment of rCDI. Furthermore, we aimed to evaluate the degree to which any methodological concerns would affect conclusions about the cost-effectiveness of FMT.<br><br>METHODS: We conducted a systematic literature review based on a search in seven medical databases up to 16 July 2020. We included research articles reporting on full health economic evaluations comparing FMT with antibiotic treatment for rCDI. General study characteristics and input estimates for costs, effectiveness and utilities were extracted from the articles. The quality of the studies was assessed by two authors using the Drummonds ten-point checklist.<br><br>RESULTS: We identified seven cost-utility analyses. All studies applied decision-analytic modelling and compared various FMT delivery methods with vancomycin, fidaxomicin, metronidazole or a combination of vancomycin and bezlotoxumab. The time horizons used in the analyses varied from 78&#x2009;days to lifelong, and the perspectives differed between a societal, a healthcare system or a third-party payer perspective. The applied willingness-to-pay threshold ranged from 20,000 to 68,000 Great Britain pound sterling (GBP) per quality-adjusted life-year (QALY). FMT was considered the most cost-effective alternative in all studies. In five of the health economic evaluations, FMT was both more effective and cost saving than antibiotic treatment alternatives. The quality of the articles varied, and we identified several methodological concerns.<br><br>CONCLUSIONS: Economic evaluations consistently reported that FMT is a cost-effective and potentially cost-saving treatment for rCDI. Based on a comparison with recent evidence within the area, the multiple methodological concerns seem not to change this conclusion. Therefore, implementing FMT for rCDI in clinical practice should be strongly considered.}, }
@article {pmid33439103, year = {2021}, author = {Cuna, A and Morowitz, MJ and Ahmed, I and Umar, S and Sampath, V}, title = {Dynamics of the preterm gut microbiome in health and disease.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {320}, number = {4}, pages = {G411-G419}, pmid = {33439103}, issn = {1522-1547}, support = {K08 DK125735/DK/NIDDK NIH HHS/United States ; R01 DK117296/DK/NIDDK NIH HHS/United States ; K08DK125735//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; }, mesh = {Animals ; Bacteria/*growth &amp; development ; Dysbiosis ; Enterocolitis, Necrotizing/*microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gestational Age ; Host-Pathogen Interactions ; Humans ; Infant, Newborn ; *Infant, Premature ; Intestines/*microbiology ; Neonatal Sepsis/*microbiology/therapy ; Prebiotics ; Probiotics/therapeutic use ; Prognosis ; Risk Factors ; }, abstract = {Advances in metagenomics have allowed a detailed study of the gut microbiome, and its role in human health and disease. Infants born prematurely possess a fragile gut microbial ecosystem that is vulnerable to perturbation. Alterations in the developing gut microbiome in preterm infants are linked to life-threatening diseases such as necrotizing enterocolitis (NEC) and late-onset sepsis; and may impact future risk of asthma, atopy, obesity, and psychosocial disease. In this mini-review, we summarize recent literature on the origins and patterns of development of the preterm gut microbiome in the perinatal period. The host-microbiome-environmental factors that portend development of dysbiotic intestinal microbial patterns associated with NEC and sepsis are reviewed. Strategies to manipulate the microbiome and mitigate dysbiosis, including the use of probiotics and prebiotics will also be discussed. Finally, we explore the challenges and future directions of gut microbiome research in preterm infants.}, }
@article {pmid33437951, year = {2020}, author = {Baunwall, SMD and Lee, MM and Eriksen, MK and Mullish, BH and Marchesi, JR and Dahlerup, JF and Hvas, CL}, title = {Faecal microbiota transplantation for recurrent Clostridioides difficile infection: An updated systematic review and meta-analysis.}, journal = {EClinicalMedicine}, volume = {29-30}, number = {}, pages = {100642}, pmid = {33437951}, issn = {2589-5370}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (CDI), but inconsistent effect rates and uncertain evidence levels have warranted caution. To clarify, we aimed to establish the evidence of FMT for recurrent CDI, updated across different delivery methods, treatment regimens, and in comparison with standard antibiotics.<br><br>METHODS: In this updated systematic review and meta-analysis, we searched PubMed, Scopus, Embase, Web of Science, Clinical Key, and Svemed+ for FMT literature published in English until November 11, 2019. We included observational and clinical trials with or without antibiotic comparators and excluded studies with below 8 weeks follow-up and fewer than 15 patients. The primary outcome was clinical outcome by week 8. We comprehensively extracted patient and procedural data. In a random-effects meta-analysis, we estimated the clinical effect for repeat or single FMT, different delivery methods, and versus antibiotics. We rated the evidence according to the Cochrane and GRADE methods. The PROSPERO preregistration number is CRD42020158112.<br><br>FINDINGS: Of 1816 studies assessed, 45 studies were included. The overall clinical effect week 8 following repeat FMT (24 studies, 1855 patients) was 91% (95% CI: 89-94%, I [2]=53%) and 84% (80-88%, I [2]=86%) following single FMT (43 studies, 2937 patients). Delivery by lower gastrointestinal endoscopy was superior to all other delivery methods, and repeat FMT significantly increased the treatment effect week 8 (P<0&#xb7;001). Compared with vancomycin, the number needed to treat (NNT) for repeat FMT was 1&#xb7;5 (1&#xb7;3-1&#xb7;9, P<0&#xb7;001) and 2.9 (1&#xb7;5-37&#xb7;1, P=0&#xb7;03) for single FMT. Repeat FMT had high quality of evidence.<br><br>INTERPRETATION: High-quality evidence supports FMT is effective for recurrent CDI, but its effect varies with the delivery method and the number of administrations. The superior NNT for FMT compared with antibiotics suggests that patients may benefit from advancing FMT to all instances of recurrent CDI.<br><br>FUNDING: Innovation Fund Denmark (j.no. 8056-00006B).}, }
@article {pmid33436437, year = {2021}, author = {Amenyogbe, N and Dimitriu, P and Smolen, KK and Brown, EM and Shannon, CP and Tebbutt, SJ and Cooper, PJ and Marchant, A and Goetghebuer, T and Esser, M and Finlay, BB and Kollmann, TR and Mohn, WW}, title = {Biogeography of the Relationship between the Child Gut Microbiome and Innate Immune System.}, journal = {mBio}, volume = {12}, number = {1}, pages = {}, pmid = {33436437}, issn = {2150-7511}, support = {/WT_/Wellcome Trust/United Kingdom ; PJT-148781//CIHR/Canada ; CMF-108029//CIHR/Canada ; 088862/Z/09/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Bacteria/*classification ; Biodiversity ; Canada ; Child, Preschool ; Cytokines/metabolism ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology/physiology ; Germ-Free Life ; Host Microbial Interactions/*immunology ; Humans ; *Immune System ; Immunity, Innate ; Infant ; Male ; Phylogeography ; Toll-Like Receptor 2 ; }, abstract = {The gut microbiome is a well-recognized modulator of host immunity, and its compositions differ between geographically separated human populations. Systemic innate immune responses to microbial derivatives also differ between geographically distinct human populations. However, the potential role of the microbiome in mediating geographically varied immune responses is unexplored. We here applied 16S amplicon sequencing to profile the stool microbiome and, in parallel, measured whole-blood innate immune cytokine responses to several pattern recognition receptor (PRR) agonists among 2-year-old children across biogeographically diverse settings. Microbiomes differed mainly between high- and low-resource environments and were not strongly associated with other demographic factors. We found strong correlations between responses to Toll-like receptor 2 (TLR2) and relative abundances of Bacteroides and Prevotella populations, shared among Canadian and Ecuadorean children. Additional correlations between responses to TLR2 and bacterial populations were specific to individual geographic cohorts. As a proof of concept, we gavaged germfree mice with human donor stools and found murine splenocyte responses to TLR stimulation were consistent with responses of the corresponding human donor populations. This study identified differences in immune responses correlating to gut microbiomes across biogeographically diverse settings and evaluated biological plausibility using a mouse model. This insight paves the way to guide optimization of population-specific interventions aimed to improve child health outcomes.IMPORTANCE Both the gut microbiome and innate immunity are known to differ across biogeographically diverse human populations. The gut microbiome has been shown to directly influence systemic immunity in animal models. With this, modulation of the gut microbiome represents an attractive avenue to improve child health outcomes associated with altered immunity using population-specific approaches. However, there are very scarce data available to determine which members of the gut microbiome are associated with specific immune responses and how these differ around the world, creating a substantial barrier to rationally designing such interventions. This study addressed this knowledge gap by identifying relationships between distinct bacterial taxa and cytokine responses to specific microbial agonists across highly diverse settings. Furthermore, we provide evidence that immunomodulatory effects of region-specific stool microbiomes can be partially recapitulated in germfree mice. This is an important contribution toward improving global child health by targeting the gut microbiome.}, }
@article {pmid33436010, year = {2021}, author = {Liu, J and Liu, C and Yue, J}, title = {Radiotherapy and the gut microbiome: facts and fiction.}, journal = {Radiation oncology (London, England)}, volume = {16}, number = {1}, pages = {9}, pmid = {33436010}, issn = {1748-717X}, support = {81871895//National Natural Science Foundation of China/ ; 2019RC003//Young Taishan Scholars and Academic Promotion Program of Shandong First Medical University/ ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*radiation effects ; Humans ; Neoplasms/*radiotherapy ; Prebiotics ; Probiotics/pharmacology ; Radiation Tolerance ; Radiotherapy/*adverse effects ; }, abstract = {An ever-growing body of evidence has linked the gut microbiome with both the effectiveness and the toxicity of cancer therapies. Radiotherapy is an effective way to treat tumors, although large variations exist among patients in tumor radio-responsiveness and in the incidence and severity of radiotherapy-induced side effects. Relatively little is known about whether and how the microbiome regulates the response to radiotherapy. Gut microbiota may be an important player in modulating "hot" versus "cold" tumor microenvironment, ultimately affecting treatment efficacy. The interaction of the gut microbiome and radiotherapy is a bidirectional function, in that radiotherapy can disrupt the microbiome and those disruptions can influence the effectiveness of the anticancer treatments. Limited data have shown that interactions between the radiation and the microbiome can have positive effects on oncotherapy. On the other hand, exposure to ionizing radiation leads to changes in the gut microbiome that contribute to radiation enteropathy. The gut microbiome can influence radiation-induced gastrointestinal mucositis through two mechanisms including translocation and dysbiosis. We propose that the gut microbiome can be modified to maximize the response to treatment and minimize adverse effects through the use of personalized probiotics, prebiotics, or fecal microbial transplantation. 16S rRNA sequencing is the most commonly used approach to investigate distribution and diversity of gut microbiome between individuals though it only identifies bacteria level other than strain level. The functional gut microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, as well as metabolomics. Multiple '-omic' approaches can be applied simultaneously to the same sample to obtain integrated results. That said, challenges and remaining unknowns in the future that persist at this time include the mechanisms by which the gut microbiome affects radiosensitivity, interactions between the gut microbiome and combination treatments, the role of the gut microbiome with regard to predictive and prognostic biomarkers, the need for multi "-omic" approach for in-depth exploration of functional changes and their effects on host-microbiome interactions, and interactions between gut microbiome, microbial metabolites and immune microenvironment.}, }
@article {pmid33435800, year = {2021}, author = {Lau, HCH and Sung, JJ and Yu, J}, title = {Gut microbiota: impacts on gastrointestinal cancer immunotherapy.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-21}, pmid = {33435800}, issn = {1949-0984}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Neoplasms/diet therapy/immunology/microbiology/*therapy ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; *Immunotherapy ; Immunotherapy, Adoptive ; Oligodeoxyribonucleotides/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {The association of gut microbiota with gastrointestinal carcinogenesis has been heavily investigated since the recent advance in sequencing technology. Accumulating evidence has revealed the critical roles of commensal microbes in cancer progression. Given by its importance, emerging studies have focussed on targeting microbiota to ameliorate therapeutic effectiveness. It is now clear that the microbial community is closely related to the efficacy of chemotherapy, while the correlation of microbiota with immunotherapy is much less studied. Herein, we review the up-to-date findings on the influence of gut microbiota on three common immunotherapies including adoptive cell transfer, immune checkpoint blockade, and CpG-oligodeoxynucleotide therapy. We then explore three microbiota-targeted strategies that may improve treatment efficacy, involving dietary intervention, probiotics supplementation, and fecal microbiota transplantation.}, }
@article {pmid33432923, year = {2021}, author = {Tyagi, AM and Darby, TM and Hsu, E and Yu, M and Pal, S and Dar, H and Li, JY and Adams, J and Jones, RM and Pacifici, R}, title = {The gut microbiota is a transmissible determinant of skeletal maturation.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33432923}, issn = {2050-084X}, support = {R01 DK112946/DK/NIDDK NIH HHS/United States ; DK112946/NH/NIH HHS/United States ; DK098391/NH/NIH HHS/United States ; R01 DK124821/DK/NIDDK NIH HHS/United States ; RR028009/NH/NIH HHS/United States ; DK108842/NH/NIH HHS/United States ; R01 DK119229/DK/NIDDK NIH HHS/United States ; R01 DK108842/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Mice ; Skeleton/*growth &amp; development ; }, abstract = {Genetic factors account for the majority of the variance of human bone mass, but the contribution of non-genetic factors remains largely unknown. By utilizing maternal/offspring transmission, cohabitation, or fecal material transplantation (FMT) studies, we investigated the influence of the gut microbiome on skeletal maturation. We show that the gut microbiome is a communicable regulator of bone structure and turnover in mice. In addition, we found that the acquisition of a specific bacterial strain, segmented filamentous bacteria (SFB), a gut microbe that induces intestinal Th17 cell expansion, was sufficient to negatively impact skeletal maturation. These findings have significant translational implications, as the identification of methods or timing of microbiome transfer may lead to the development of bacteriotherapeutic interventions to optimize skeletal maturation in humans. Moreover, the transfer of SFB-like microbes capable of triggering the expansion of human Th17 cells during therapeutic FMT procedures could lead to significant bone loss in fecal material recipients.}, }
@article {pmid33428780, year = {2021}, author = {Citraro, R and Lembo, F and De Caro, C and Tallarico, M and Coretti, L and Iannone, LF and Leo, A and Palumbo, D and Cuomo, M and Buommino, E and Nesci, V and Marascio, N and Iannone, M and Quirino, A and Russo, R and Calignano, A and Constanti, A and Russo, E and De Sarro, G}, title = {First evidence of altered microbiota and intestinal damage and their link to absence epilepsy in a genetic animal model, the WAG/Rij rat.}, journal = {Epilepsia}, volume = {62}, number = {2}, pages = {529-541}, doi = {10.1111/epi.16813}, pmid = {33428780}, issn = {1528-1167}, support = {2015XSZ9A2//Italian Ministry of University and Research (MIUR)/ ; 2017B9NCSX//Italian Ministry of University and Research (MIUR)/ ; 2017YZF7MA//Italian Ministry of University and Research (MIUR)/ ; GR-2013-02355028//Italian Ministry of Health/ ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Anticonvulsants/*pharmacology ; Bacteroidetes ; Butyrates/metabolism ; Colon/pathology ; DNA, Bacterial/analysis ; DNA, Ribosomal/genetics ; Disease Models, Animal ; Electroencephalography ; Epilepsy, Absence/genetics/*microbiology/physiopathology/therapy ; Ethosuximide/pharmacology ; Fatty Acids, Volatile/metabolism ; *Fecal Microbiota Transplantation ; Firmicutes ; Gastrointestinal Microbiome/*drug effects/*genetics ; Gastrointestinal Motility ; Haptoglobins/metabolism ; Ileum/pathology ; Propionates/metabolism ; Protein Precursors/metabolism ; Proteobacteria ; Rats ; Rats, Wistar ; Seizures/genetics/microbiology/physiopathology ; }, abstract = {OBJECTIVE: A large number of studies have highlighted the important role of the gut microbiota in the pathophysiology of neurological disorders, suggesting that its manipulation might serve as a treatment strategy. We hypothesized that the gut microbiota participates in absence seizure development and maintenance in the WAG/Rij rat model and tested this hypothesis by evaluating potential gut microbiota and intestinal alterations in the model, as well as measuring the impact of microbiota manipulation using fecal microbiota transplantation (FMT).<br><br>METHODS: Initially, gut microbiota composition and intestinal histology of WAG/Rij rats (a well-recognized genetic model of absence epilepsy) were studied at 1, 4, and 8 months of age in comparison to nonepileptic Wistar rats. Subsequently, in a second set of experiments, at 6 months of age, untreated Wistar or WAG/Rij rats treated with ethosuximide (ETH) were used as gut microbiota donors for FMT in WAG/Rij rats, and electroencephalographic (EEG) recordings were obtained over 4&#xa0;weeks. At the end of FMT, stool and gut samples were collected, absence seizures were measured on EEG recordings, and microbiota analysis and histopathological examinations were performed.<br><br>RESULTS: Gut microbiota analysis showed differences in beta diversity and specific phylotypes at all ages considered and significant variances in the Bacteroidetes/Firmicutes ratio between Wistar and WAG/Rij rats. FMT, from both Wistar and ETH-treated WAG/Rij donors to WAG/Rij rats, significantly decreased the number and duration of seizures. Histological results indicated that WAG/Rij rats were characterized by intestinal villi disruption and inflammatory infiltrates already at 1 month of age, before seizure occurrence; FMT partially restored intestinal morphology while also significantly modifying gut microbiota and concomitantly reducing absence seizures.<br><br>SIGNIFICANCE: Our results demonstrate for the first time that the gut microbiota is modified and contributes to seizure occurrence in a genetic animal model of absence epilepsy and that its manipulation may be a suitable therapeutic target for absence seizure management.}, }
@article {pmid33427793, year = {2021}, author = {Jain, V and Alexander, EC and Burford, C and Verma, A and Dhawan, A}, title = {Gut Microbiome: A Potential Modifiable Risk Factor in Biliary Atresia.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {72}, number = {2}, pages = {184-193}, doi = {10.1097/MPG.0000000000002973}, pmid = {33427793}, issn = {1536-4801}, mesh = {Adult ; *Biliary Atresia/etiology ; Child ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Infant ; Risk Factors ; }, abstract = {Biliary atresia (BA) is a fibro-obliterative condition of the biliary tree, presenting in infancy. The bilioenteric conduit formed at Kasai portoenterostomy (KPE), achieves restoration of bile flow in approximately 60% of infants. Even if the operation is successful, cirrhosis and its associated complications are, however, common. BA remains the leading cause for liver transplantation (LT) in children. Antibiotic, choleretic, and steroid therapy post-KPE have not convincingly reduced LT rates. Advances in molecular technology have enabled characterisation of the encoded genes of the gut microbiota (gut microbiome). The gut microbiome plays an important role in host metabolism, nutrition, and immune function, with alterations in its diversity and/or composition, known as dysbiosis, being described in disease states, including liver disease. Liver-gut microbiome exploration in adulthood largely focuses on nonalcoholic liver disease, cirrhosis (mainly alcohol- or viral-based aetiology) and cholestatic liver diseases (eg, primary sclerosing cholangitis), with microbial signatures correlating to disease severity. Investigation of the gut microbiota in BA had been limited to culture-based methodology, but molecular studies are emerging, and although in their infancy, highlight a potential pathogenic role for Enterobacteriaceae and Streptococcus, and a potential beneficial role for Bifidobacteria. Bacterial translocation, and the production of gut microbiome-derived metabolites, are key host-microbiome-mechanistic pathways in liver disease pathogenesis. Microbiome-targeted therapeutics for liver disease are in development, with faecal microbiota transplantation showing promise in cirrhosis. Could the gut microbiome be a novel modifiable risk factor in BA, reducing the need for LT?}, }
@article {pmid33427531, year = {2021}, author = {Khanna, S}, title = {Advances in Clostridioides difficile therapeutics.}, journal = {Expert review of anti-infective therapy}, volume = {19}, number = {9}, pages = {1067-1070}, doi = {10.1080/14787210.2021.1874919}, pmid = {33427531}, issn = {1744-8336}, mesh = {Anti-Bacterial Agents/administration &amp; dosage ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/microbiology/*therapy ; Fecal Microbiota Transplantation/methods ; Humans ; Recurrence ; }, }
@article {pmid33424650, year = {2020}, author = {Zhao, HJ and Luo, X and Shi, YC and Li, JF and Pan, F and Ren, RR and Peng, LH and Shi, XY and Yang, G and Wang, J and Hu, LY and Zou, LP and Yang, YS}, title = {The Efficacy of Fecal Microbiota Transplantation for Children With Tourette Syndrome: A Preliminary Study.}, journal = {Frontiers in psychiatry}, volume = {11}, number = {}, pages = {554441}, pmid = {33424650}, issn = {1664-0640}, abstract = {Therapies for Tourette syndrome (TS) are insufficient, and novel therapies are needed. Fecal microbiota transplantation (FMT) has been a potential therapy for several neurological diseases. Here, we report a preliminary study to investigate the effects of FMT on patients with TS. Five patients with TS received a single administration of FMT via endoscopy. Tic symptoms were assessed by Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) and adverse effects were recorded at week 8 following FMT. Lipopolysaccharide (LPS) levels and 14 cytokines levels were measured. The microbiota profile in feces were analyzed by shotgun metagenomics. Four patients (4/5) responded positively to FMT (YGTSS-TTS reduction rate >25%) at week 8 with high safety. The levels of LPS and cytokines varied after FMT. FMT shifted the composition of the gut microbiota in patients close to that of the donor and continuously changed the abundance of Bacteroides coprocola, Dialister succinatiphilus and Bacteroides vulgatus. The restoration of B.coprocola was correlated with the improvement in tic symptoms (Spearman R = -0.900, P = 0.037). In conclusion, FMT was indicated a potential effective and safe alternative for patients with TS. However, larger clinical trials are needed to confirm the influence of microbiota in TS. Trial Registration: chictr.org.cn Identifier: ChiCTR-IIR-17011871, URL: http://www.chictr.org.cn/showproj.aspx?proj=19941.}, }
@article {pmid33422641, year = {2021}, author = {Pu, Y and Tan, Y and Qu, Y and Chang, L and Wang, S and Wei, Y and Wang, X and Hashimoto, K}, title = {A role of the subdiaphragmatic vagus nerve in depression-like phenotypes in mice after fecal microbiota transplantation from Chrna7 knock-out mice with depression-like phenotypes.}, journal = {Brain, behavior, and immunity}, volume = {94}, number = {}, pages = {318-326}, doi = {10.1016/j.bbi.2020.12.032}, pmid = {33422641}, issn = {1090-2139}, mesh = {Animals ; *Depression ; *Fecal Microbiota Transplantation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; Vagus Nerve ; alpha7 Nicotinic Acetylcholine Receptor/genetics ; }, abstract = {The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR: coded by Chrna7) regulates the cholinergic ascending anti-inflammatory pathway involved in depression. We previously reported that Chrna7 knock-out (KO) mice show depression-like phenotypes through systemic inflammation. In this study, we investigated whether fecal microbiota transplantation (FMT) from Chrna7 KO mice causes depression-like phenotypes in mice treated with an antibiotic cocktail (ABX). Chrna7 KO mice with depression-like phenotypes show an abnormal gut microbiota composition, although the alpha diversity and beta diversity were not altered. FMT from Chrna7 KO mice caused depression-like phenotypes, systemic inflammation, and downregulation of synaptic proteins in the prefrontal cortex (PFC) in the ABX-treated mice compared to FMT from the control mice. The Principal component analysis based on the OTU level showed that the FMT group from the KO mice were different from the FMT group from the control mice. We found differences in abundance for several bacteria in the FMT group from the KO mice at the taxonomic level when compared with the other group. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of depression-like phenotypes in the ABX-treated mice after FMT from Chrna7 KO mice. These data suggest that FMT from Chrna7 KO mice produce depression-like phenotypes in ABX-treated mice via the subdiaphragmatic vagus nerve. The brain-gut-microbiota axis association with the subdiaphragmatic vagus nerve plays an important role in the development of depression.}, }
@article {pmid33422116, year = {2021}, author = {Ashiri, A and Rafiei, A and Beiromvand, M and Khanzadeh, A and Alghasi, A}, title = {Screening of Strongyloides stercoralis infection in high-risk patients in Khuzestan Province, Southwestern Iran.}, journal = {Parasites &amp; vectors}, volume = {14}, number = {1}, pages = {37}, pmid = {33422116}, issn = {1756-3305}, support = {OG/9834//Ahvaz Jundishapur University of Medical Sciences/ ; }, mesh = {Adult ; Animals ; Asthma ; Cross-Sectional Studies ; Diagnostic Tests, Routine/methods ; Enzyme-Linked Immunosorbent Assay ; Feces/parasitology ; Female ; Formaldehyde ; Humans ; Immunocompromised Host ; Iran/epidemiology ; Ivermectin/therapeutic use ; Male ; Mass Screening ; Middle Aged ; Polymerase Chain Reaction ; Prevalence ; Pulmonary Disease, Chronic Obstructive ; Risk Factors ; Soil ; *Strongyloides stercoralis/isolation &amp; purification ; Strongyloidiasis/diagnosis/drug therapy/*epidemiology/*parasitology ; Young Adult ; }, abstract = {BACKGROUND: Strongyloidiasis, one of the neglected tropical diseases (NTDs), can be fatal in immunocompromised patients. Available data on Strongyloides stercoralis infection in high-risk patients in Iran are limited. The aim of the present study was to determine the prevalence of S. stercoralis infection and associated risk factors among high-risk patients as well as to evaluate the sensitivity of the diagnostic tests used in the diagnose of S. stercoralis infection.<br><br>METHODS: This cross-sectional study was performed from 2019 to 2020 among 300 high-risk patients in Khuzestan Province, southwestern Iran. Patients with autoimmune diseases, uncontrolled diabetes, HIV/AIDS, cancer, organ transplant, hematological malignancy, asthma and chronic obstructive pulmonary disease (COPD) were examined using direct smear examination, formalin-ether concentration, Baermann funnel technique, agar plate culture, and ELISA test. Since agar plate culture was considered the reference diagnostic test, culture-positive samples were confirmed by PCR amplification and the sequencing of the nuclear 18S rDNA (SSU) hypervariable region (HVRIV) of the parasite.<br><br>RESULTS: The prevalence of S. stercoralis infection was 1%, 1.3%, 2%, 2.7%, and 8.7% using direct smear examination, formalin-ether concentration, Baermann funnel technique, agar plate culture, and ELISA test, respectively. All culture-positive samples were confirmed by SSU-PCR. According to the results, the most sensitive test was ELISA, with 100% sensitivity, followed by the Baermann funnel technique with the sensitivity of 75%. Direct smear examination, formalin-ether concentration technique, and Baermann funnel technique had the highest PPV (100%) while the ELISA test had the highest NPV (100%). Significant eosinophilia was observed in the patients whose culture test was positive (7/8; P&#x2009;<&#x2009;0.05). In the present study, the majority of the positive cases by the agar plate culture had a history of prolonged exposure to soil and of asthma and COPD and were > 60 years old.<br><br>CONCLUSIONS: Given that the ELISA test had the highest NPV, the screening of all high-risk patients for S. stercoralis infection in endemic areas is recommended prior to starting corticosteroid therapy with the ELISA test. The results indicate the importance of paying attention to patients with unknown eosinophilia in endemic areas. Ivermectin should be available to strongyloidiasis patients in the endemic areas.}, }
@article {pmid33421190, year = {2021}, author = {Helve, O and Andersson, S}, title = {Giving faecal transplants to infants born by Caesarean section produced similar gut microbiotica results to vaginal deliveries.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {110}, number = {5}, pages = {1393-1394}, doi = {10.1111/apa.15734}, pmid = {33421190}, issn = {1651-2227}, mesh = {*Cesarean Section ; Delivery, Obstetric ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Parturition ; Pregnancy ; }, }
@article {pmid33420959, year = {2021}, author = {Allegretti, JR and Kassam, Z and Hurtado, J and Marchesi, JR and Mullish, BH and Chiang, A and Thompson, CC and Cummings, BP}, title = {Impact of fecal microbiota transplantation with capsules on the prevention of metabolic syndrome among patients with obesity.}, journal = {Hormones (Athens, Greece)}, volume = {20}, number = {1}, pages = {209-211}, pmid = {33420959}, issn = {2520-8721}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; R21 AT010956/AT/NCCIH NIH HHS/United States ; Junior Faculty Developement Award//Brigham and Women's Hospital/ ; }, mesh = {Adult ; Fecal Microbiota Transplantation/*methods ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Metabolic Syndrome/*etiology/*prevention &amp; control ; Middle Aged ; Obesity/*complications ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been studied for the treatment of metabolic syndrome with varying success. However, the possibility of utilizing FMT to prevent metabolic syndrome is to date unknown.<br><br>METHODS: Secondary analysis of a previously published double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients was conducted. Post-prandial glucose and insulin levels were measured (NCT02741518).<br><br>RESULTS: A total of 22 patients were enrolled, 11 in each arm. There were no baseline differences in the area under the curve (AUC) of glucose or insulin in the FMT group compared to placebo. There was a significant change in glucose AUC at week 12 compared to baseline, and in the insulin AUC at week 6 compared to baseline in the FMT group vs. placebo (change in glucose AUC (mg/dl&#x2009;&#xd7;&#x2009;60&#xa0;min): 579 vs 1978, p&#x2009;=&#x2009;0.03) (change in insulin AUC (&#x3bc;U/ml&#x2009;&#xd7;&#x2009;60&#xa0;min): 137 vs 2728, p&#x2009;=&#x2009;0.01).<br><br>CONCLUSIONS: These data suggest that FMT may have a potential role in preventing the development of metabolic syndrome in patients with obesity.}, }
@article {pmid33420064, year = {2021}, author = {Kim, HS and Whon, TW and Sung, H and Jeong, YS and Jung, ES and Shin, NR and Hyun, DW and Kim, PS and Lee, JY and Lee, CH and Bae, JW}, title = {Longitudinal evaluation of fecal microbiota transplantation for ameliorating calf diarrhea and improving growth performance.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {161}, pmid = {33420064}, issn = {2041-1723}, mesh = {Animals ; Bacteroidaceae/genetics/isolation &amp; purification ; Cattle/*growth &amp; development/microbiology ; Cattle Diseases/blood/metabolism/microbiology/*therapy ; DNA, Bacterial/isolation &amp; purification ; Diarrhea/blood/metabolism/microbiology/*therapy ; Fecal Microbiota Transplantation/*veterinary ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/*genetics ; Genomics ; Male ; Metabolomics ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {Calf diarrhea is associated with enteric infections, and also provokes the overuse of antibiotics. Therefore, proper treatment of diarrhea represents a therapeutic challenge in livestock production and public health concerns. Here, we describe the ability of a fecal microbiota transplantation (FMT), to ameliorate diarrhea and restore gut microbial composition in 57 growing calves. We conduct multi-omics analysis of 450 longitudinally collected fecal samples and find that FMT-induced alterations in the gut microbiota (an increase in the family Porphyromonadaceae) and metabolomic profile (a reduction in fecal amino acid concentration) strongly correlate with the remission of diarrhea. During the continuous follow-up study over 24 months, we find that FMT improves the growth performance of the cattle. This first FMT trial in ruminants suggest that FMT is capable of ameliorating diarrhea in pre-weaning calves with alterations in their gut microbiota, and that FMT may have a potential role in the improvement of growth performance.}, }
@article {pmid33418488, year = {2021}, author = {Iyama, S and Tatsumi, H and Shiraishi, T and Yoshida, M and Tatekoshi, A and Endo, A and Ishige, T and Shiwa, Y and Ibata, S and Goto, A and Nagashima, K and Horiguchi, H and Fujita, C and Ikeda, H and Takada, K and Nobuoka, T and Kamihara, Y and Kikuchi, S and Sato, T and Ohnishi, H and Yokota, SI and Kobune, M}, title = {Possible clinical outcomes using early enteral nutrition in individuals with allogeneic hematopoietic stem cell transplantation: A single-center retrospective study.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {83}, number = {}, pages = {111093}, doi = {10.1016/j.nut.2020.111093}, pmid = {33418488}, issn = {1873-1244}, mesh = {Enteral Nutrition ; *Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation ; Humans ; RNA, Ribosomal, 16S/genetics ; Retrospective Studies ; }, abstract = {OBJECTIVES: Intensive nutritional support during allogeneic hematopoietic stem cell transplantation (allo-HSCT) yields improved clinical outcomes. However, the clinical implications of early enteral nutrition (EN) in allo-HSCT remain unclear. This retrospective study was conducted to determine the significance of early EN in individuals who underwent allo-HSCT, and the association between early nutritional intervention and clinical outcomes, including the status of the intestinal microbiome.<br><br>METHODS: Thirty-one participants received EN before conditioning. The intestinal microbiota was examined by meta 16S rRNA gene sequencing of fecal samples.<br><br>RESULTS: The median body mass variation was only -0.35 kg on day 60. The probability of 2-y overall survival was 61.1%. The cumulative incidence of treatment-related mortality was 17.4%, and those of acute graft-versus-host disease were 32.3% (grades II-IV) and 3.2% (grades III-IV). Chronic graft-versus-host disease was observed in four participants. Dysbiosis of the intestines and acute graft-versus-host disease occurred simultaneously, and Enterococcus species were abundant.<br><br>CONCLUSIONS: Our results suggest that early nutritional support can improve the outcomes for individuals who have undergone allo-HSCT and can maintain homeostasis of their intestinal microbiome. Future prospective clinical trials are required to elucidate the role of EN in allo-HSCT and the association between the intestinal microbiome and EN.}, }
@article {pmid33416044, year = {2020}, author = {Carbone, EA and D'Amato, P and Vicchio, G and De Fazio, P and Segura-Garcia, C}, title = {A systematic review on the role of microbiota in the pathogenesis and treatment of eating disorders.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {64}, number = {1}, pages = {e2}, pmid = {33416044}, issn = {1778-3585}, mesh = {Affect ; Anorexia Nervosa/microbiology/psychology/therapy ; Binge-Eating Disorder/microbiology/psychology/therapy ; Brain/physiopathology ; Bulimia Nervosa/microbiology/psychology/therapy ; Feeding and Eating Disorders/*microbiology/psychology/*therapy ; Gastrointestinal Microbiome/*physiology ; Humans ; Psychopathology ; Satiety Response ; }, abstract = {BACKGROUND: There is growing interest in new factors contributing to the genesis of eating disorders (EDs). Research recently focused on the study of microbiota. Dysbiosis, associated with a specific genetic susceptibility, may contribute to the development of anorexia nervosa (AN), bulimia nervosa, or binge eating disorder, and several putative mechanisms have already been identified. Diet seems to have an impact not only on modification of the gut microbiota, facilitating dysbiosis, but also on its recovery in patients with EDs.<br><br>METHODS: This systematic review based on the PICO strategy searching into PubMed, EMBASE, PsychINFO, and Cochrane Library examined the literature on the role of altered microbiota in the pathogenesis and treatment of EDs.<br><br>RESULTS: Sixteen studies were included, mostly regarding AN. Alpha diversity and short-chain fatty acid (SCFA) levels were lower in patients with AN, and affective symptoms and ED psychopathology seem related to changes in gut microbiota. Microbiota-derived proteins stimulated the autoimmune system, altering neuroendocrine control of mood and satiety in EDs. Microbial richness increased in AN after weight regain on fecal microbiota transplantation.<br><br>CONCLUSIONS: Microbiota homeostasis seems essential for a healthy communication network between gut and brain. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center contributing to the pathophysiological development of EDs. A restored microbial balance may be a possible treatment target for EDs. A better and more in-depth characterization of gut microbiota and gut-brain crosstalk is required. Future studies may deepen the therapeutic and preventive role of microbiota in EDs.}, }
@article {pmid33414033, year = {2021}, author = {Fuhri Snethlage, CM and Nieuwdorp, M and Hanssen, NMJ}, title = {Faecal microbiota transplantation in endocrine diseases and obesity.}, journal = {Best practice &amp; research. Clinical endocrinology &amp; metabolism}, volume = {35}, number = {3}, pages = {101483}, doi = {10.1016/j.beem.2020.101483}, pmid = {33414033}, issn = {1878-1594}, mesh = {*Diabetes Mellitus, Type 2/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Insulin Resistance ; Obesity/therapy ; }, abstract = {The prevalence of type 1 (T1D) and type 2 diabetes mellitus (T2D) has greatly increased worldwide over the last century. Although the exact pathophysiology of both these conditions is distinct and still largely unknown, T1D as well as T2D, have been linked to distinct perturbations of the gut microbiome. Faecal microbiota transplantation (FMT) is a potent, and if performed well, a safe method to modulate the composition of the gut microbiome and thus positively influences the course of these hyperglycaemic conditions in humans. In this review, we provide an overview of how FMT is commonly performed and summarise how this procedure may reduce the insulin-resistance driving T2D, and the underlying auto-immunity driving T1D. Insights derived from FMT studies in T1D and T2D may help identify beneficial microbiota and associated metabolites that may serve as future treatments for these conditions.}, }
@article {pmid33410638, year = {2021}, author = {Venick, RS}, title = {Grant monitoring after intestinal transplantation.}, journal = {Current opinion in organ transplantation}, volume = {26}, number = {2}, pages = {234-239}, pmid = {33410638}, issn = {1531-7013}, mesh = {Biomarkers ; Feces ; Graft Rejection/prevention &amp; control ; Humans ; *Intestinal Diseases/surgery ; Intestines ; Tissue Donors ; }, abstract = {PURPOSE OF REVIEW: The current review aims to describe in detail the most common practices utilized to monitor graft function in intestinal transplant (ITx) recipients. In addition, to discussing the role of endoscopy and stool studies it will examine the use of other potential biomarkers which have been utilized. Data will be discussed from contemporary publications in the field, the Intestinal Transplant Registry as well as detailed data from a large, ITx single-center.<br><br>RECENT FINDINGS: Significant improvements have been made in early outcomes following ITx, yet long-term survival remains challenged by infection and rejection, both of which can present with diarrhea. While endoscopy and stool studies are the gold-standard for graft monitoring, calprotectin, citrulline, measurements of immunoreactivity and donor-specific antibodies have been investigated in the field and are herein reviewed.<br><br>SUMMARY: Despite a number of tests which are currently available for monitoring ITx recipients, a strong need exists for improved noninvasive, timely and accurate biomarkers to help improve ITx graft and patient survival.}, }
@article {pmid33409398, year = {2021}, author = {Kwong, EK and Puri, P}, title = {Gut microbiome changes in Nonalcoholic fatty liver disease &amp; alcoholic liver disease.}, journal = {Translational gastroenterology and hepatology}, volume = {6}, number = {}, pages = {3}, pmid = {33409398}, issn = {2415-1289}, support = {F30 AA026470/AA/NIAAA NIH HHS/United States ; K23 AA021179/AA/NIAAA NIH HHS/United States ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are some of the most common liver diseases worldwide. The human gut microbiome is dynamic and shifts in bacterial composition have been implicated in many diseases. Studies have shown that there is a shift in bacterial overgrowth favoring pro-inflammatory mediators in patients with advanced disease progression such as cirrhosis. Further investigation demonstrated that the transplantation of gut microbiota from advanced liver disease patients can reproduce severe liver inflammation and injury in mice. Various techniques in manipulating the gut microbiota have been attempted including fecal transplantation and probiotics. This review focuses on the changes in the gut microbiota as well as emerging lines of microbiome work with respect to NAFLD and ALD.}, }
@article {pmid33405294, year = {2020}, author = {Donovan, C and Liu, G and Shen, S and Marshall, JE and Kim, RY and Alemao, CA and Budden, KF and Choi, JP and Kohonen-Corish, M and El-Omar, EM and Yang, IA and Hansbro, PM}, title = {The role of the microbiome and the NLRP3 inflammasome in the gut and lung.}, journal = {Journal of leukocyte biology}, volume = {108}, number = {3}, pages = {925-935}, doi = {10.1002/JLB.3MR0720-472RR}, pmid = {33405294}, issn = {1938-3673}, mesh = {Aging/immunology ; Air Pollutants/toxicity ; Animals ; Asthma/immunology ; Cigarette Smoking/immunology ; Colitis/immunology/microbiology/therapy ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Furans ; Gastrointestinal Microbiome/*immunology ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Humans ; Indenes ; Inflammasomes/*immunology ; Inflammation/*immunology ; Intestines/*immunology ; Lung/*immunology ; Mice ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/antagonists &amp; inhibitors/deficiency/*physiology ; Pneumonia, Bacterial/immunology ; Pneumonia, Viral/immunology ; Pulmonary Disease, Chronic Obstructive/immunology ; Specific Pathogen-Free Organisms ; Sulfonamides ; Sulfones/pharmacology ; Symbiosis ; }, abstract = {The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is one of the most well-characterized inflammasomes, activated by pathogen-associated molecular patterns and damage-associated molecular patterns, including from commensal or pathogenic bacterial and viral infections. The NLRP3 inflammasome promotes inflammatory cell recruitment and regulates immune responses in tissues such as the gastrointestinal tract and the lung, and is involved in many diseases that affect the gut and lung. Recently, the microbiome in the gut and the lung, and the crosstalk between these organs (gut-lung axis), has been identified as a potential mechanism that may influence disease in a bidirectional manner. In this review, we focus on themes presented in this area at the 2019 World Congress on Inflammation. We discuss recent evidence on how the microbiome can affect NLRP3 inflammasome responses in the gut and lung, the role of this inflammasome in regulating gut and lung inflammation in disease, and its potential role in the gut-lung axis. We highlight the exponential increase in our understanding of the NLRP3 inflammasome due to the synthesis of the NLRP3 inflammasome inhibitor, MCC950, and propose future studies that may further elucidate the roles of the NLRP3 inflammasome in gut and lung diseases.}, }
@article {pmid33399770, year = {2020}, author = {Quera, R and Sedano, R and Núñez, P}, title = {[Is fecal microbiota transplantation currently a therapeutic option in patients with irritable bowel syndrome?].}, journal = {Revista medica de Chile}, volume = {148}, number = {5}, pages = {713-714}, doi = {10.4067/S0034-98872020000500713}, pmid = {33399770}, issn = {0717-6163}, mesh = {*Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Treatment Outcome ; }, }
@article {pmid33399007, year = {2022}, author = {Ramírez-Macías, I and Orenes-Piñero, E and Camelo-Castillo, A and Rivera-Caravaca, JM and López-García, C and Marín, F}, title = {Novel insights in the relationship of gut microbiota and coronary artery diseases.}, journal = {Critical reviews in food science and nutrition}, volume = {62}, number = {14}, pages = {3738-3750}, doi = {10.1080/10408398.2020.1868397}, pmid = {33399007}, issn = {1549-7852}, mesh = {*Atherosclerosis ; Bacteria/metabolism ; *Coronary Artery Disease/complications ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics ; }, abstract = {Atherosclerosis is a chronic, progressive, inflammatory disease in the vasculature and is common in both coronary and peripheral arteries. Human beings harbor a complex and dynamic population of microorganisms defined as the microbiota. Importantly, alterations in the bacterial composition (dysbiosis) and the metabolic compounds produced by these bacteria have been associated with the pathogenesis of many inflammatory diseases and infections. There is also a close relationship between intestinal microbiota and cardiovascular diseases. The aim of this review was to analyze how changes in the gut microbiota and their metabolites might affect coronary artery diseases. The most representative groups of bacteria that make up the intestinal microbiota are altered in coronary artery disease patients, resulting in a decrease in Bacteroidetes and an increase in Firmicutes. In relation to metabolites, trimethylamine-N-oxide plays an important role in atherosclerosis and may act as a cardiovascular risk predictor. In addition, the use of probiotics, prebiotics, diet modulation, and fecal transplantation, which may represent alternative treatments for these diseases, is thoroughly discussed. Finally, the role of lipid-lowering treatments is also analyzed as they may affect and alter the gut microbiota and, conversely, gut microbiota diversity could be associated with resistance or sensitivity to these treatments.}, }
@article {pmid33397897, year = {2021}, author = {Zhang, F and Zuo, T and Yeoh, YK and Cheng, FWT and Liu, Q and Tang, W and Cheung, KCY and Yang, K and Cheung, CP and Mo, CC and Hui, M and Chan, FKL and Li, CK and Chan, PKS and Ng, SC}, title = {Longitudinal dynamics of gut bacteriome, mycobiome and virome after fecal microbiota transplantation in graft-versus-host disease.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {65}, pmid = {33397897}, issn = {2041-1723}, mesh = {Adolescent ; Biodiversity ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Graft vs Host Disease/*microbiology/*virology ; Humans ; Male ; Microbiota ; *Mycobiome ; *Virome ; }, abstract = {Fecal microbiota transplant (FMT) has emerged as a potential treatment for severe colitis associated with graft-versus-host disease (GvHD) following hematopoietic stem cell transplant. Bacterial engraftment from FMT donor to recipient has been reported, however the fate of fungi and viruses after FMT remains unclear. Here we report longitudinal dynamics of the gut bacteriome, mycobiome and virome in a teenager with GvHD after receiving four doses of FMT at weekly interval. After serial FMTs, the gut bacteriome, mycobiome and virome of the patient differ from compositions before FMT with variable temporal dynamics. Diversity of the gut bacterial community increases after each FMT. Gut fungal community initially shows expansion of several species followed by a decrease in diversity after multiple FMTs. In contrast, gut virome community varies substantially over time with a stable rise in diversity. The bacterium, Corynebacterium jeikeium, and Torque teno viruses, decrease after FMTs in parallel with an increase in the relative abundance of Caudovirales bacteriophages. Collectively, FMT may simultaneously impact on the various components of the gut microbiome with distinct effects.}, }
@article {pmid33397500, year = {2021}, author = {LaPelusa, M and Donoviel, D and Branzini, SE and Carlson, PE and Culler, S and Cheema, AK and Kaddurah-Daouk, R and Kelly, D and de Cremoux, I and Knight, R and Krajmalnik-Brown, R and Mayo, SL and Mazmanian, SK and Mayer, EA and Petrosino, JF and Garrison, K}, title = {Microbiome for Mars: surveying microbiome connections to healthcare with implications for long-duration human spaceflight, virtual workshop, July 13, 2020.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {2}, pmid = {33397500}, issn = {2049-2618}, mesh = {Animals ; *Astronauts ; Delivery of Health Care/*trends ; Gastrointestinal Microbiome/genetics/physiology ; Humans ; *Mars ; Microbiota/genetics/*physiology ; *Space Flight ; }, abstract = {The inaugural "Microbiome for Mars" virtual workshop took place on July 13, 2020. This event assembled leaders in microbiome research and development to discuss their work and how it may relate to long-duration human space travel. The conference focused on surveying current microbiome research, future endeavors, and how this growing field could broadly impact human health and space exploration. This report summarizes each speaker's presentation in the order presented at the workshop.}, }
@article {pmid33391458, year = {2021}, author = {Liu, Y and Cavallaro, PM and Kim, BM and Liu, T and Wang, H and Kühn, F and Adiliaghdam, F and Liu, E and Vasan, R and Samarbafzadeh, E and Farber, MZ and Li, J and Xu, M and Mohad, V and Choi, M and Hodin, RA}, title = {A role for intestinal alkaline phosphatase in preventing liver fibrosis.}, journal = {Theranostics}, volume = {11}, number = {1}, pages = {14-26}, pmid = {33391458}, issn = {1838-7640}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; T32 DK007754/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Alkaline Phosphatase/*genetics/*metabolism ; Animals ; Carbon Tetrachloride/toxicity ; Common Bile Duct/surgery ; Disease Models, Animal ; Feces/chemistry ; Female ; GPI-Linked Proteins/metabolism ; Humans ; Ileum/metabolism ; Intestines ; Ligation ; Lipopolysaccharides ; Liver Cirrhosis/etiology/*genetics/metabolism ; Male ; Mice ; Mice, Knockout ; Middle Aged ; Permeability ; Tight Junction Proteins/genetics ; Toll-Like Receptor 4/*genetics ; }, abstract = {Rationale: Liver fibrosis is frequently associated with gut barrier dysfunction, and the lipopolysaccharides (LPS) -TLR4 pathway is common to the development of both. Intestinal alkaline phosphatase (IAP) has the ability to detoxify LPS, as well as maintain intestinal tight junction proteins and gut barrier integrity. Therefore, we hypothesized that IAP may function as a novel therapy to prevent liver fibrosis. Methods: Stool IAP activity from cirrhotic patients were determined. Common bile duct ligation (CBDL) and Carbon Tetrachloride-4 (CCl4)-induced liver fibrosis models were used in WT, IAP knockout (KO), and TLR4 KO mice supplemented with or without exogenous IAP in their drinking water. The gut barrier function and liver fibrosis markers were tested. Results: Human stool IAP activity was decreased in the setting of liver cirrhosis. In mice, IAP activity and genes expression decreased after CBDL and CCl4 exposure. Intestinal tight junction related genes and gut barrier function were impaired in both models of liver fibrosis. Oral IAP supplementation attenuated the decrease in small intestine tight junction protein gene expression and gut barrier function. Liver fibrosis markers were significantly higher in IAP KO compared to WT mice in both models, while oral IAP rescued liver fibrosis in both WT and IAP KO mice. In contrast, IAP supplementation did not attenuate fibrosis in TLR4 KO mice in either model. Conclusions: Endogenous IAP is decreased during liver fibrosis, perhaps contributing to the gut barrier dysfunction and worsening fibrosis. Oral IAP protects the gut barrier and further prevents the development of liver fibrosis via a TLR4-mediated mechanism.}, }
@article {pmid33387699, year = {2021}, author = {Moniot, M and Nourrisson, C and Faure, C and Delbac, F and Favennec, L and Dalle, F and Garrouste, C and Poirier, P}, title = {Assessment of a Multiplex PCR for the Simultaneous Diagnosis of Intestinal Cryptosporidiosis and Microsporidiosis: Epidemiologic Report from a French Prospective Study.}, journal = {The Journal of molecular diagnostics : JMD}, volume = {23}, number = {4}, pages = {417-423}, doi = {10.1016/j.jmoldx.2020.12.005}, pmid = {33387699}, issn = {1943-7811}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Cryptosporidiosis/*diagnosis/*epidemiology/parasitology ; Cryptosporidium/*genetics/isolation &amp; purification ; Diarrhea/microbiology/parasitology ; Encephalitozoon/*genetics/isolation &amp; purification ; Enterocytozoon/*genetics/isolation &amp; purification ; Feces/microbiology/parasitology ; Female ; France/epidemiology ; Genotype ; Humans ; Immunocompromised Host ; Infant ; Infant, Newborn ; Male ; Microsporidiosis/*diagnosis/*epidemiology/microbiology ; Middle Aged ; Multiplex Polymerase Chain Reaction/*methods ; Prevalence ; Prospective Studies ; Real-Time Polymerase Chain Reaction/*methods ; Sensitivity and Specificity ; Young Adult ; }, abstract = {Microsporidiosis and cryptosporidiosis are associated with chronic diarrhea in immunocompromised patients. The objectives of this study were to: i) assess a multiplex quantitative PCR assay targeting Cryptosporidium spp and the microsporidian Enterocytozoon bieneusi and Encephalitozoon spp, and ii) provide an update on the epidemiology of these pathogens. A prospective study was conducted from January 2017 to January 2019. Performance of the assay was assessed, and all cryptosporidia and microsporidia isolates were genotyped. The sensitivity of the multiplex PCR method reached 1 copy/μL for each targeted pathogen. The sensitivity of co-proantigen testing in the diagnosis of cryptosporidiosis was 73%. The sensitivity of microscopy in the diagnosis of cryptosporidiosis was 64%, and microsporidiosis, 50%. Among the 456 patients included, 14 were positive for Cryptosporidium spp (4 different species); 5, for E. bieneusi; and 2, for Encephalitozoon intestinalis. The overall prevalence of cryptosporidia was 3.1%, and of microsporidia, 1.5%; in kidney transplant recipients (n = 82), corresponding values were 7.3% and 2.4% (6 and 2 patients), respectively. Two cases of E. intestinalis infection were diagnosed in children who had traveled to the tropics. This study is the first to assess a multiplex quantitative PCR method for the simultaneous diagnosis of intestinal microsporidiosis and cryptosporidiosis. The highest prevalences of both pathogens were observed in kidney transplant recipients.}, }
@article {pmid33387530, year = {2021}, author = {Kummen, M and Thingholm, LB and Rühlemann, MC and Holm, K and Hansen, SH and Moitinho-Silva, L and Liwinski, T and Zenouzi, R and Storm-Larsen, C and Midttun, &#xd8; and McCann, A and Ueland, PM and Høivik, ML and Vesterhus, M and Trøseid, M and Laudes, M and Lieb, W and Karlsen, TH and Bang, C and Schramm, C and Franke, A and Hov, JR}, title = {Altered Gut Microbial Metabolism of Essential Nutrients in Primary Sclerosing Cholangitis.}, journal = {Gastroenterology}, volume = {160}, number = {5}, pages = {1784-1798.e0}, pmid = {33387530}, issn = {1528-0012}, support = {802544/ERC_/European Research Council/International ; }, mesh = {Adolescent ; Adult ; Aged ; Bacteria/genetics/*metabolism ; Case-Control Studies ; Cholangitis, Sclerosing/blood/diagnosis/*microbiology/surgery ; Cross-Sectional Studies ; Dysbiosis ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Germany ; Humans ; Liver Transplantation ; Male ; *Metabolome ; Metabolomics ; *Metagenome ; Metagenomics ; Middle Aged ; Norway ; Phylogeny ; Progression-Free Survival ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: To influence host and disease phenotype, compositional microbiome changes, which have been demonstrated in patients with primary sclerosing cholangitis (PSC), must be accompanied by functional changes. We therefore aimed to characterize the genetic potential of the gut microbiome in patients with PSC compared with healthy controls (HCs) and patients with inflammatory bowel disease (IBD).<br><br>METHODS: Fecal DNA from 2 cohorts (1 Norwegian and 1 German), in total comprising 136 patients with PSC (58% with IBD), 158 HCs, and 93 patients with IBD without PSC, were subjected to metagenomic shotgun sequencing, generating 17 billion paired-end sequences, which were processed using HUMAnN2 and MetaPhlAn2, and analyzed using generalized linear models and random effects meta-analyses.<br><br>RESULTS: Patients with PSC had fewer microbial genes compared with HCs (P < .0001). Compared with HCs, patients with PSC showed enrichment and increased prevalence of Clostridium species and a depletion of, for example, Eubacterium spp and Ruminococcus obeum. Patients with PSC showed marked differences in the abundance of genes related to vitamin B6 synthesis and branched-chain amino acid synthesis (Qfdr < .05). Targeted metabolomics of plasma from an independent set of patients with PSC and controls found reduced concentrations of vitamin B6 and branched-chain amino acids in PSC (P < .0001), which strongly associated with reduced liver transplantation-free survival (log-rank P < .001). No taxonomic or functional differences were detected between patients with PSC with and without IBD.<br><br>CONCLUSIONS: The gut microbiome in patients with PSC exhibits large functional differences compared with that in HCs, including microbial metabolism of essential nutrients. Alterations in related circulating metabolites associated with disease course, suggesting that microbial functions may be relevant for the disease process in PSC.}, }
@article {pmid33387515, year = {2021}, author = {Olesen, SW}, title = {Fecal Microbiota Transplantation "Donor Effects" Are Not Clinically Relevant for Clostridioides difficile Infection.}, journal = {Gastroenterology}, volume = {160}, number = {7}, pages = {2635-2636}, doi = {10.1053/j.gastro.2020.12.057}, pmid = {33387515}, issn = {1528-0012}, mesh = {*Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation ; Humans ; Tissue Donors ; }, }
@article {pmid33387212, year = {2021}, author = {Zhou, G and Zeng, J and Peng, L and Wang, L and Zheng, W and Di Wu,  and Yang, Y}, title = {Fecal microbiota transplantation for membranous nephropathy.}, journal = {CEN case reports}, volume = {10}, number = {2}, pages = {261-264}, pmid = {33387212}, issn = {2192-4449}, mesh = {Chronic Disease ; Diarrhea/complications/therapy ; *Fecal Microbiota Transplantation ; Glomerulonephritis, Membranous/complications/*therapy ; Humans ; Treatment Outcome ; }, abstract = {Membranous nephropathy is a pathological type of nephrotic syndrome. Current treatments including supportive therapy, corticosteroids, immunosuppressive agents are not effective for all patients. New therapies are needed to treat the disease safely and effectively. Gut microbiota may contribute to the pathogenesis of this disease. Fecal microbiota transplantation (FMT) has made achievements in many diseases. Here, we report a case in which FMT is used to treat a patient with membranous nephropathy and chronic diarrhea, whose symptoms ameliorated and renal function improved.}, }
@article {pmid33383805, year = {2020}, author = {Vuuren, MJV and Nell, TA and Carr, JA and Kell, DB and Pretorius, E}, title = {Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson's Disease.}, journal = {Biomolecules}, volume = {11}, number = {1}, pages = {}, pmid = {33383805}, issn = {2218-273X}, support = {NNF10CC1016517//The Novo Nordisk Foundation/International ; A0X331//Medical Research Council of South Africa (MRC)/International ; }, mesh = {Animals ; Dysbiosis/complications/*metabolism/physiopathology ; Gastrointestinal Microbiome ; Humans ; Inflammation/complications/*metabolism/physiopathology ; Iron/*metabolism ; Mouth/microbiology ; Oxidative Stress ; Parkinson Disease/etiology/*metabolism/physiopathology ; alpha-Synuclein/metabolism ; }, abstract = {Neuronal lesions in Parkinson's disease (PD) are commonly associated with α-synuclein (α-Syn)-induced cell damage that are present both in the central and peripheral nervous systems of patients, with the enteric nervous system also being especially vulnerable. Here, we bring together evidence that the development and presence of PD depends on specific sets of interlinking factors that include neuroinflammation, systemic inflammation, α-Syn-induced cell damage, vascular dysfunction, iron dysregulation, and gut and periodontal dysbiosis. We argue that there is significant evidence that bacterial inflammagens fuel this systemic inflammation, and might be central to the development of PD. We also discuss the processes whereby bacterial inflammagens may be involved in causing nucleation of proteins, including of α-Syn. Lastly, we review evidence that iron chelation, pre-and probiotics, as well as antibiotics and faecal transplant treatment might be valuable treatments in PD. A most important consideration, however, is that these therapeutic options need to be validated and tested in randomized controlled clinical trials. However, targeting underlying mechanisms of PD, including gut dysbiosis and iron toxicity, have potentially opened up possibilities of a wide variety of novel treatments, which may relieve the characteristic motor and nonmotor deficits of PD, and may even slow the progression and/or accompanying gut-related conditions of the disease.}, }
@article {pmid33383647, year = {2020}, author = {Weinstein, N and Garten, B and Vainer, J and Minaya, D and Czaja, K}, title = {Managing the Microbiome: How the Gut Influences Development and Disease.}, journal = {Nutrients}, volume = {13}, number = {1}, pages = {}, pmid = {33383647}, issn = {2072-6643}, support = {1R01DC013904//The National Institutes of Health/ ; }, mesh = {Animals ; Cecum ; *Disease ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/microbiology/physiology ; Germ-Free Life ; *Growth and Development ; Humans ; Microbiota ; Models, Animal ; Research Design ; Research Personnel ; }, abstract = {The microbiome lies at the forefront of scientific research, as researchers work to uncover its mysterious influence on human development and disease. This paper reviews how the microbiome is studied, how researchers can improve its study, and what clinical applications microbiome research might yield. For this review, we analyzed studies concerning the role of the microbiome in disease and early development, the common methodologies by which the microbiome is researched in the lab, and modern clinical treatments for dysbiosis and their possible future applications. We found that the gut microbiome is essential for proper development of various physiological systems and that gut dysbiosis is a clear factor in the etiology of various diseases. Furthermore, we found that germ-free animal models and microbiome manipulation techniques are inadequate, reducing the efficacy of microbiome research. Nonetheless, research continues to show the significance of microbiome manipulation in the clinical treatment of disease, having shown great promise in the prevention and treatment of dysbiosis. Though the clinical applications of microbiome manipulation are currently limited, the significance of dysbiosis in the etiology of a wide array of diseases indicates the significance of this research and highlights the need for more effective research methods concerning the microbiome.}, }
@article {pmid33383113, year = {2021}, author = {Han, C and Jiang, YH and Li, W and Liu, Y}, title = {Astragalus membranaceus and Salvia miltiorrhiza ameliorates cyclosporin A-induced chronic nephrotoxicity through the "gut-kidney axis".}, journal = {Journal of ethnopharmacology}, volume = {269}, number = {}, pages = {113768}, doi = {10.1016/j.jep.2020.113768}, pmid = {33383113}, issn = {1872-7573}, mesh = {Animals ; Astragalus propinquus/*chemistry ; Butyric Acid ; Colon/drug effects/metabolism/microbiology/pathology ; Cyclosporine/toxicity ; Drugs, Chinese Herbal/*pharmacology/therapeutic use ; Endoplasmic Reticulum Stress/drug effects ; Fatty Acids/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Lactic Acid ; Male ; Medicine, Chinese Traditional ; Mice, Inbred C57BL ; MicroRNAs/drug effects/metabolism ; Oxidative Stress/drug effects ; RNA, Messenger/drug effects/metabolism ; Receptors, Cell Surface/drug effects ; Renal Insufficiency, Chronic/chemically induced/*drug therapy/microbiology/pathology ; Salvia miltiorrhiza/*chemistry ; Mice ; }, abstract = {The combination of Astragalus membranaceus and Salvia miltiorrhiza (AS) is an effective prescription that is widely used to treat chronic kidney disease (CKD) clinically in traditional Chinese medicine. Our previous studies have shown that AS can alleviate early CKD through the "gut-kidney axis", but the regulatory role of AS in the "gut-kidney axis" in the middle and late stages of CKD caused by cyclosporin A-induced chronic nephrotoxicity (CICN) has remained unclear.<br><br>AIM OF THE STUDY: To explore the protective effect of AS by regulating the intestinal flora to further control the miRNA-mRNA interaction profiles in CICN.<br><br>MATERIALS AND METHODS: Thirty-two mice were divided into four groups: Normal (N) (olive oil), Model (M) (CsA, 30&#xa0;mg&#xa0;kg[-1] d[-1]), AS (CsA&#xa0;+&#xa0;AS, 30&#xa0;+&#xa0;8.4&#xa0;g&#xa0;kg[-1] d[-1]) and FMT-AS (CsA&#xa0;+&#xa0;Faeces of AS group, 30&#xa0;mg&#xa0;+&#xa0;10&#xa0;mL&#xa0;kg[-1] d[-1]). The mice were treated for 6 weeks. Changes in renal function related metabolites were detected, pathological changes in the colon and kidney were observed, and 16S rDNA sequencing was performed on mouse faeces. In addition, miRNA and mRNA sequencing were performed on the kidney to construct differential expression (DE) profiles of the other 3 groups compared with group M. The target mRNAs among the DE miRNAs were then predicted, and an integrated analysis was performed with the DE mRNAs to annotate gene function by KEGG. DE miRNAs and DE mRNAs related to CICN in the overlapping top 20 KEGG pathways were screened and verified.<br><br>RESULTS: Eight metabolites that could worsen renal function were increased in group M, accompanied by thickening of the glomerular basement membrane, vacuolar degeneration of renal tubules, and proliferation of collagen fibres, while AS and FMT-AS intervention amended these changes to varying degrees. Simultaneously, intestinal permeability increased, the abundance and diversity of the flora decreased, and the ratio of Firmicum to Bacteroides (F/B) increased in group M. The AS and FMT-AS treatments reversed the flora disorder and increased probiotics producing butyric acid and lactic acid, especially Akkermansia and Lactobacillus, which might regulate the 12 overlapping top 20 KEGG pathways, such as Butanoate metabolism, Tryptophan metabolism and several RF-related pathways, leading to the remission of renal metabolism. Finally, 15 DE miRNAs and 45 DE mRNAs were screened as the therapeutic targets, and the results coincided with the sequencing results.<br><br>CONCLUSION: AS could alleviate renal fibrosis and metabolism caused by CICN through the "gut-kidney axis". Probiotics such as Akkermansia and Lactobacillus were the primary driving factors, and the miRNA-mRNA interaction profiles, especially Butanoate metabolism and Tryptophan metabolism, may be an important subsequent response and regulatory mechanism.}, }
@article {pmid33382952, year = {2021}, author = {Brunse, A and Offersen, SM and Mosegaard, JJ and Deng, L and Damborg, P and Nielsen, DS and Sangild, PT and Thymann, T and Nguyen, DN}, title = {Enteral broad-spectrum antibiotics antagonize the effect of fecal microbiota transplantation in preterm pigs.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-16}, pmid = {33382952}, issn = {1949-0984}, mesh = {Animals ; Animals, Newborn ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacterial Adhesion/drug effects ; Combined Modality Therapy ; Disease Models, Animal ; Drug Resistance, Microbial/drug effects ; Enterocolitis, Necrotizing/immunology/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects ; Immunity, Mucosal/drug effects ; Intubation, Gastrointestinal ; Lymphocytes/drug effects ; Myeloid Cells/drug effects ; Premature Birth ; Swine ; Treatment Outcome ; }, abstract = {Preterm infants are at risk of multiple morbidities including necrotizing enterocolitis (NEC). Suspected NEC patients receive intravenous antibiotics (AB) to prevent sepsis, although enteral AB is arguably more effective at reducing NEC but is rarely used due to the risk of AB resistance. Fecal microbiota transplantation (FMT) has shown protective effects against NEC in animal experiments, but the interaction between AB and FMT has not been investigated in neonates. We hypothesized that administration of enteral AB followed by rectal FMT would effectively prevent NEC with negligible changes in AB resistance and systemic immunity. Using preterm piglets, we examined host and gut microbiota responses to AB, FMT, or a sequential combination thereof, with emphasis on NEC development. In a saline-controlled experiment, preterm piglets (n = 67) received oro-gastric neomycin (50 mg/kg/d) and amoxicillin-clavulanate (50/12.5 mg/kg/d) (hereafter AB) for four days after cesarean delivery, and were subsequently given rectal FMT from healthy suckling piglet donors. Whereas AB protected the stomach and small intestine, and FMT primarily protected the colon, the sequential combination treatment surprisingly provided no NEC protection. Furthermore, minor changes in the gut microbiota composition were observed in response to either treatment, although AB treatment decreased species diversity and increased AB resistance among coliform bacteria and Enterococci, which were both partly reversed by FMT. Besides, enteral AB treatment suppressed cellular and functional systemic immune development, which was not prevented by subsequent FMT. We discovered an antagonistic relationship between enteral AB and FMT in terms of NEC development. The outcome may depend on choice of AB compounds, FMT composition, doses, treatment duration, and administration routes, but these results challenge the applicability of enteral AB and FMT in preterm infants.}, }
@article {pmid33382932, year = {2020}, author = {Chang, JT}, title = {Pathophysiology of Inflammatory Bowel Diseases.}, journal = {The New England journal of medicine}, volume = {383}, number = {27}, pages = {2652-2664}, doi = {10.1056/NEJMra2002697}, pmid = {33382932}, issn = {1533-4406}, mesh = {Fecal Microbiota Transplantation ; Host Microbial Interactions/physiology ; Humans ; Inflammatory Bowel Diseases/genetics/immunology/*physiopathology/therapy ; Interleukins/physiology ; Intestinal Mucosa/*immunology/physiopathology ; T-Lymphocytes/physiology ; }, }
@article {pmid33382364, year = {2021}, author = {Xia, WJ and Xu, ML and Yu, XJ and Du, MM and Li, XH and Yang, T and Li, L and Li, Y and Kang, KB and Su, Q and Xu, JX and Shi, XL and Wang, XM and Li, HB and Kang, YM}, title = {Antihypertensive effects of exercise involve reshaping of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rat.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-24}, pmid = {33382364}, issn = {1949-0984}, mesh = {Animals ; Blood Pressure ; Brain-Gut Axis/*physiology ; Cardiomegaly/prevention &amp; control ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/*physiology ; Gastrointestinal Tract/metabolism/pathology ; Hypertension/pathology/*therapy ; Inflammation/prevention &amp; control ; Male ; Microglia/metabolism ; Paraventricular Hypothalamic Nucleus/pathology ; Permeability ; Physical Conditioning, Animal/*physiology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Sympathetic Nervous System/pathology ; }, abstract = {Exercise (Ex) has long been recognized to produce beneficial effects on hypertension (HTN). This coupled with evidence of gut dysbiosis and an impaired gut-brain axis led us to hypothesize that reshaping of gut microbiota and improvement in impaired gut-brain axis would, in part, be associated with beneficial influence of exercise. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise for 12 weeks, whereas, detrained groups underwent 8 weeks of moderate-intensity exercise followed by 4 weeks of detraining. Fecal microbiota, gut pathology, intestinal inflammation, and permeability, brain microglia and neuroinflammation were analyzed. We observed that exercise training resulted in a persistent decrease in systolic blood pressure in the SHR. This was associated with increase in microbial α diversity, altered β diversity, and enrichment of beneficial bacterial genera. Furthermore, decrease in the number of activated microglia, neuroinflammation in the hypothalamic paraventricular nucleus, improved gut pathology, inflammation, and permeability were also observed in the SHR following exercise. Interestingly, short-term detraining did not abolish these exercise-mediated improvements. Finally, fecal microbiota transplantation from exercised SHR into sedentary SHR resulted in attenuated SBP and an improved gut-brain axis. These observations support our concept that an impaired gut-brain axis is linked to HTN and exercise ameliorates this impairment to induce antihypertensive effects.}, }
@article {pmid33382360, year = {2021}, author = {Huus, KE and Frankowski, M and Pučić-Baković, M and Vučković, F and Lauc, G and Mullish, BH and Marchesi, JR and Monaghan, TM and Kao, D and Finlay, BB}, title = {Changes in IgA-targeted microbiota following fecal transplantation for recurrent Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-12}, pmid = {33382360}, issn = {1949-0984}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; FDN-159935//CIHR/Canada ; }, mesh = {Adult ; Aged ; Clostridioides difficile ; Clostridium Infections/metabolism/*microbiology/therapy ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Homeostasis ; Humans ; Immunoglobulin A, Secretory/*metabolism ; Male ; Middle Aged ; Recurrence ; Tissue Donors ; Treatment Outcome ; }, abstract = {Secretory immunoglobulin A (IgA) interacts with intestinal microbiota and promotes mucosal homeostasis. IgA-bacteria interactions are altered during inflammatory diseases, but how these interactions are shaped by bacterial, host, and environmental factors remains unclear. In this study, we utilized IgA-SEQ to profile IgA-bound fecal bacteria in 48 recurrent Clostridioides difficile patients before and after successful fecal microbiota transplantation (FMT) to gain further insight. Prior to FMT, Escherichia coli was the most highly IgA-targeted taxon; following restoration of the microbiota by FMT, highly IgA-targeted taxa included multiple Firmicutes species. Post-FMT IgA-targeting was unaffected by the route of FMT delivery (colonoscopy versus capsule), suggesting that both methods lead to the establishment of healthy immune-bacterial interactions in the gut. Interestingly, IgA-targeting in FMT recipients closely resembled the IgA-targeting patterns of the donors, and fecal donor identity was significantly associated with IgA-targeting of the recipient microbiota. These data support the concept that intrinsic bacterial properties drive IgA recognition across genetically distinct human hosts. Together, this study suggests that IgA-bacterial interactions are reestablished in human FMT recipients to resemble that of the healthy fecal donor.}, }
@article {pmid33382357, year = {2020}, author = {Lu, XY and Han, B and Deng, X and Deng, SY and Zhang, YY and Shen, PX and Hui, T and Chen, RH and Li, X and Zhang, Y}, title = {Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1857515}, pmid = {33382357}, issn = {1949-0984}, mesh = {Animals ; Bacteria/classification/*drug effects/genetics/growth &amp; development ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/*drug therapy/microbiology ; Female ; Fruit/chemistry ; Gastrointestinal Microbiome/*drug effects ; Humans ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis/*drug therapy/microbiology ; Plant Extracts/*administration &amp; dosage/chemistry ; Pomegranate/*chemistry ; Waste Products/*analysis ; }, abstract = {Multiple sclerosis (MS) is a CNS autoimmune disease characterized by demyelination and inflammatory infiltration with a high disability rate. Increasing evidence has demonstrated the importance of gut microbiota as an environmental risk factor in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Diet is the main determinant of gut microbiota composition and function, which greatly affects the shaping of microbial structure. Pomegranate peel, a waste product in the production of juice, is rich in health-promoting compounds. However, its individual constituents, immunoregulatory activities, and action associated with bacterial diversity in the gut microbiota are largely unknown. Here, the main nutrient ingredients of pomegranate peel extract (PPE) were identified as phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins via metabolomics evaluation. We found, for the first time, oral PPE (100 mg/kg/day) not only effectively relieves EAE, inhibits CNS inflammatory factor infiltration and myelin loss, but also reshapes gut microbiota. Furthermore, recipient EAE mice with fecal transplantation from the PPE-treated donor delayed the disease development significantly. 16S rRNA gene sequencing revealed the increased gut microbiota richness in PPE-treated group. Among them, Lactobacillaceae enriched significantly, while Alcaligenaceae and Acidaminococcacea decreased remarkably. In conclusion, our data demonstrated that gut microbiota mediated the beneficial effects of oral PPE on EAE, and provided new ideas for developing the prebiotic value of pomegranate peel for the treatment of autoimmune diseases.}, }
@article {pmid33381671, year = {2021}, author = {Rizk, MG and Thackray, VG}, title = {Intersection of Polycystic Ovary Syndrome and the Gut Microbiome.}, journal = {Journal of the Endocrine Society}, volume = {5}, number = {2}, pages = {bvaa177}, pmid = {33381671}, issn = {2472-1972}, support = {K12 GM068524/GM/NIGMS NIH HHS/United States ; P50 HD012303/HD/NICHD NIH HHS/United States ; R01 HD095412/HD/NICHD NIH HHS/United States ; T32 HD007203/HD/NICHD NIH HHS/United States ; }, abstract = {The etiology of polycystic ovary syndrome (PCOS) remains unclear, although studies indicate that both genetic and environmental factors contribute to the syndrome. In 2012, Tremellen and Pearce proposed the idea that dysbiosis of the intestinal (gut) microbiome is a causative factor of metabolic and reproductive manifestations of PCOS. In the past 5 years, studies in both humans and rodent models have demonstrated that changes in the taxonomic composition of gut bacteria are associated with PCOS. Studies have also clearly shown that these changes in gut microbiota are associated with PCOS as opposed to obesity, since these changes are observed in women with PCOS that are both of a normal weight or obese, as well as in adolescent girls with PCOS and obesity compared with body mass index- and age-matched females without the disorder. Additionally, studies in both women with PCOS and rodent models of PCOS demonstrated that hyperandrogenism is associated with gut microbial dysbiosis, indicating that androgens may modulate the gut microbial community in females. One study reported that the fecal microbiome transplantation of stool from women with PCOS or exposure to certain bacteria resulted in a PCOS-like phenotype in mice, while other studies showed that exposure to a healthy gut microbiome, pre/probiotics, or specific gut metabolites resulted in protection from developing PCOS-like traits in mice. Altogether, these results suggest that dysbiosis of the gut microbiome may be sufficient to develop PCOS-like symptoms and that modulation of the gut microbiome may be a potential therapeutic target for PCOS.}, }
@article {pmid33381475, year = {2020}, author = {Chi, X and Pan, CQ and Liu, S and Cheng, D and Cao, Z and Xing, H}, title = {Regulating Intestinal Microbiota in the Prevention and Treatment of Alcohol-Related Liver Disease.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {2020}, number = {}, pages = {6629196}, pmid = {33381475}, issn = {2291-2797}, mesh = {Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Liver Diseases, Alcoholic/prevention &amp; control ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {When alcohol-related liver disease occurs, the number and composition ratio of intestinal microorganisms will accordingly change. The alcohol-induced changes in the intestinal microbiota play a pivotal role in the process of developing the alcohol-related liver disease through the translocation of microbial products due to increased intestinal permeability. In recent years, therapeutic interventions with a concentration on regulating intestinal microbiota have been conducted for patients with alcohol-related liver disease. We aimed to provide a critical review and updates on the prevention and treatment of alcohol-related liver disease through regulating intestinal microbiota. A literature search was performed on the PubMed database for studies published in English about the therapeutic intervention with microbiota using animal models and patients with alcohol-related liver disease (1/2010-4/2020). The accumulating pieces of evidence suggest that the therapeutic use of probiotics, prebiotics, antibiotics, phages, or fecal microbial transplantation may have several influences on alcohol-related liver disease patients. Emergent data unveiled that these interventions can further regulate the composition of intestinal microbiota, minimize the negative impact of microbiota on the liver, and prevent disease progression from mild to severe alcoholic hepatitis, fibrosis, cirrhosis, or even liver cancer. The current review provides updates on the advances of therapeutic interventions with the effects of regulating intestinal microbiota on patients who have alcohol-related liver disease. In addition, the data gaps and research directions on further exploration of the role of intestinal microbiota for the management of the alcohol-related liver disease are also discussed.}, }
@article {pmid33377562, year = {2021}, author = {Guilfoyle, J and Considine, J and Bouchoucha, SL}, title = {Faecal microbiota transplantation and the patient experience: A systematic review.}, journal = {Journal of clinical nursing}, volume = {30}, number = {9-10}, pages = {1236-1252}, doi = {10.1111/jocn.15625}, pmid = {33377562}, issn = {1365-2702}, mesh = {*Fecal Microbiota Transplantation ; Humans ; }, abstract = {AIM: To review and synthesise the literature examining the patients' experience of faecal microbiota transplantation.<br><br>BACKGROUND: Faecal microbiota transplantation is a common treatment for many conditions, including Clostridium Difficile infections. Patients' experience of treatments is an important influence on clinical decision-making and treatment adherence.<br><br>DESIGN: The PRISMA guidelines guided this systematic review. The review was registered with PROSPERO [CRD42020140446].<br><br>METHOD: A search of Cumulative Index of Nursing and Allied Health Literature, Medline and Embase was conducted for studies published in English and French up to June 2020. Risk of bias was examined using Critical Appraisal Skills Program tools, and quality appraisal was performed independently by three reviewers. Primary outcome of interest was the patient experience of faecal microbiota transplantation. Data were synthesised using a narrative approach.<br><br>RESULTS: The search identified 3316 citations, and 12 studies were included. Methodological quality of studies was moderate to low quality. Few studies have accurately explored the patients' experience of faecal microbiota transplantation: most focus on clinical outcomes or hypothetical scenarios regarding the patients' perspectives of faecal microbiota transplantation. Only one study was identified where the sole focus was the patients' experience of faecal microbiota transplantation. Patient's experience of faecal microbiota transplantation was diverse and complex with physiological and psychological components dependent on the patient's medical condition, the administration method and the efficacy.<br><br>CONCLUSION: Patients did not find faecal microbiota transplantation unappealing; however, patients equally reported the procedural experience was unpleasant. Limited results and low quality evidence suggest that further evaluation of the patient experience of faecal microbiota transplantation would be beneficial.<br><br>Identifying the patients' experience of faecal microbiota transplantation may inform recommendations regarding alternate treatment therapies and enable opportunities to provide quality care for patients that require faecal microbiota transplantation.}, }
@article {pmid33377391, year = {2022}, author = {Ling, Z and Liu, X and Cheng, Y and Yan, X and Wu, S}, title = {Gut microbiota and aging.}, journal = {Critical reviews in food science and nutrition}, volume = {62}, number = {13}, pages = {3509-3534}, doi = {10.1080/10408398.2020.1867054}, pmid = {33377391}, issn = {1549-7852}, mesh = {Aging ; Dysbiosis ; *Gastrointestinal Microbiome/physiology ; *Healthy Aging ; Humans ; *Immunosenescence ; }, abstract = {Aging is characterized by the functional decline of tissues and organs and increased risk of aging-associated disorders, which pose major societal challenges and are a public health priority. Despite extensive human genetics studies, limited progress has been made linking genetics with aging. There is a growing realization that the altered assembly, structure and dynamics of the gut microbiota actively participate in the aging process. Age-related microbial dysbiosis is involved in reshaping immune responses during aging, which manifest as immunosenescence (insufficiency) and inflammaging (over-reaction) that accompany many age-associated enteric and extraenteric diseases. The gut microbiota can be regulated, suggesting a potential target for aging interventions. This review summarizes recent findings on the physiological succession of gut microbiota across the life-cycle, the roles and mechanisms of gut microbiota in healthy aging, alterations of gut microbiota and aging-associated diseases, and the gut microbiota-targeted anti-aging strategies.}, }
@article {pmid33377094, year = {2020}, author = {Alavi, S and Hsiao, A}, title = {Protocol for Microbiome Transplantation in Suckling Mice during Vibrio cholerae Infection to Study Commensal-Pathogen Interactions.}, journal = {STAR protocols}, volume = {1}, number = {3}, pages = {100200}, pmid = {33377094}, issn = {2666-1667}, support = {R35 GM124724/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn ; Cholera/*microbiology ; *Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/physiology ; Host-Pathogen Interactions ; Humans ; Mice ; Microbial Interactions ; Microbiota/physiology ; Symbiosis ; Vibrio cholerae/pathogenicity ; }, abstract = {The gut microbiome plays an important role in the exclusion of pathogens and, thus, infection outcomes. Microbiome-pathogen interaction studies are complicated by a lack of tractable animal models and differences in animal model versus human microbiomes. We have adapted the suckling mouse model of infection of the human pathogen Vibrio cholerae to clear murine microbes and establish human-associated gut microbes during infection. Our method allows for the easy examination of the contribution of different human microbial communities to enteropathogenesis. For complete details on the use and execution of this protocol, please refer to Alavi et al. (2020).}, }
@article {pmid33376261, year = {2020}, author = {Sharma, AP and Burton, J and Filler, G and Dave, S}, title = {Current update and future directions on gut microbiome and nephrolithiasis.}, journal = {Indian journal of urology : IJU : journal of the Urological Society of India}, volume = {36}, number = {4}, pages = {262-269}, pmid = {33376261}, issn = {0970-1591}, abstract = {The incidence of nephrolithiasis is increasing worldwide. Understanding how gut microbiome influences oxalate homeostasis has the potential to offer new strategies to prevent nephrolithiasis. The literature was reviewed to gather the evidence on the association between gut microbiome, hyperoxaluria and nephrolithiasis, and to identify the therapeutic interventions focused on the gut microbiome that could decrease hyperoxaluria and prevent nephrolithiasis. Gut microbiome is constituted by a plethora of microbiota including Oxalobacter formigenes (Oxf) and lactobacilli. Oxf can degrade dietary oxalate and induce enteral oxalate secretion. Animal studies suggested an association between oral Oxf supplementation and a decrease in hyperoxaluria. However, human studies have showed inconsistent results. Oral supplementation of lactobacilli did not show benefit in decreasing the hyperoxaluria. Antibiotic exposure, by affecting the gut microbiome, has been associated with an increase in nephrolithiasis. In vivo studies suggest fecal transplantation as a potential treatment option for reducing nephrolithiasis, but needs further evaluation in clinical studies. The current evidence suggests an association between gut microbiome and nephrolithiasis. However, the strategies focused on modulating gut microbiome for decreasing hyperoxaluria and preventing nephrolithiasis need further research. Judicious use of antibiotics in those predisposed to nephrolithiasis offers a preventative strategy for decreasing nephrolithiasis.}, }
@article {pmid33363184, year = {2020}, author = {Yang, H and Cai, R and Kong, Z and Chen, Y and Cheng, C and Qi, S and Gu, B}, title = {Teasaponin Ameliorates Murine Colitis by Regulating Gut Microbiota and Suppressing the Immune System Response.}, journal = {Frontiers in medicine}, volume = {7}, number = {}, pages = {584369}, pmid = {33363184}, issn = {2296-858X}, abstract = {Background: Dietary intervention is an exciting topic in current research of inflammatory bowel disease (IBD). The effect of teasaponin (TS) on IBD has not been fully elucidated. Here, we aim to investigate the intestinal anti-inflammatory activity of TS in a dextran sodium sulfate (DSS)-induced colitis mouse model and identify potential mechanisms. Methods: We applied TS to mice with DSS-induced colitis and then monitored the body weight, disease activity index (DAI) daily. When sacrificed, the intestinal permeability was measured. The analysis of mucin and tight junction proteins was conducted. We detected the inflammatory cytokines, the immune cells and related inflammatory signaling pathways. In addition, the gut microbiota were analyzed by 16S rRNA sequencing and we also performed fecal microbiota transplantation (FMT). Results: It showed that TS ameliorated the colonic damage by lowering the DAI, prolonging the colon length, reducing inflammatory cytokines and improving the mucus barrier. Parallel to down-regulation of the inflammatory cytokines, the fecal lipocalin 2, p-P65, p-STAT3, and neutrophil accumulation were also decreased in TS-treated mice. Microbiota characterization showed that Campylobacteria, Proteobacteria, Helicobacter, and Enterobacteriaceae were the key bacteria associated with IBD. In addition, TS could reverse the Firmicutes/Bacteroidetes (F/B) ratio and increase the beneficial bacteria, including Akkermansia and Bacteroides. TS ameliorated DSS-induced colitis by regulating the gut microbiota, and the gut microbiota could regulate gut inflammation. Conclusions: These studies demonstrated that TS ameliorated murine colitis through the modulation of immune response, mucus barrier and gut microbiota, thus improving gut dysbiosis. In addition, the gut microbiota may play an important role in regulating the host's innate immune system, and the two coexist and are mutually beneficial. We provide a promising perspective on the clinical treatment of IBD.}, }
@article {pmid33360370, year = {2021}, author = {Tang, J and Xu, L and Zeng, Y and Gong, F}, title = {Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4/NF-kB signaling pathway.}, journal = {International immunopharmacology}, volume = {91}, number = {}, pages = {107272}, doi = {10.1016/j.intimp.2020.107272}, pmid = {33360370}, issn = {1878-1705}, mesh = {Acute Lung Injury/chemically induced/metabolism/microbiology/*prevention &amp; control ; Animals ; Anti-Bacterial Agents/toxicity ; Bacteria/drug effects/immunology/*metabolism ; Disease Models, Animal ; Dysbiosis ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Host-Pathogen Interactions ; Inflammation Mediators/metabolism ; Intestines/drug effects/*microbiology ; Lipopolysaccharides ; Lung/immunology/*metabolism/pathology ; Mice, Inbred C57BL ; NF-kappa B/*metabolism ; Oxidative Stress ; Signal Transduction ; Toll-Like Receptor 4/*metabolism ; Mice ; }, abstract = {Acute lung injury (ALI) is a common acute respiratory disease treated in the clinic. Intestinal microflora disorder affect lung diseases through the gut-lung axis. In this study, we explored the regulatory mechanism of the gut flora in the host defense against lipopolysaccharide (LPS)-induced ALI through the TLR4/NF-kB pathway by constructing a gut microflora dysbiosis-model with antibiotic administration and reconstruction of the intestinal microecology. Then, high-throughput sequencing was performed, and the levels of secreted IgA (sIgA), β-defensins, and Muc2 were measured to assess the gut flora and mucosal barrier. The expression of TLR4, NF-kB, TNF-α, IL-1β, oxidative stress and the lung wet/dry (W/D) ratio were evaluated to assess lung damage. Hematoxylin and eosin (HE) staining was performed to evaluate the damage to the gut and lung tissues. Accordingly, gut microbiota imbalance may regulate the TLR4/NF-kB signaling pathway in the lung immune system, activating oxidative stress in the lung and mediating lung injury through the regulation of the gut barrier. However, fecal microbiota transplantation (FMT) impairs the activity of the TLR4/NF-kB signaling pathway in the lung and decreases oxidative stress in animals with ALI by restoring the gut microecology. CONCLUSIONS: Our results indicated the protective effect of gut flora in regulating immunity of LPS-induced ALI by modulating the TLR4/NF-kB signaling pathway which may induce inflammation and oxidative stress.}, }
@article {pmid33358585, year = {2021}, author = {Wu, W and Shen, N and Luo, L and Deng, Z and Chen, J and Tao, Y and Mo, X and Cao, Q}, title = {Fecal microbiota transplantation before hematopoietic stem cell transplantation in a pediatric case of chronic diarrhea with a FOXP3 mutation.}, journal = {Pediatrics and neonatology}, volume = {62}, number = {2}, pages = {172-180}, doi = {10.1016/j.pedneo.2020.11.003}, pmid = {33358585}, issn = {2212-1692}, mesh = {Child, Preschool ; Chronic Disease ; Diabetes Mellitus, Type 1/*congenital/genetics/therapy ; Diarrhea/etiology/genetics/*therapy ; *Fecal Microbiota Transplantation ; Forkhead Transcription Factors/*genetics ; Genetic Diseases, X-Linked/genetics/*therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Immune System Diseases/*congenital/genetics/therapy ; Male ; *Mutation ; }, abstract = {BACKGROUND: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder caused by mutation of the forkhead box protein 3 (FOXP3) gene, often leading to intractable and life-threatening diarrhea. Fecal microbiota transplantation (FMT), has been regarded in recent years as an available approach to reconstruct disrupted gut microbiome and successfully used to attenuates diarrhea induced by different underlying diseases. Therefore, FMT may have curative potential on the symptoms of enteropathy in patients with IPEX syndrome.<br><br>METHODS: Physical and laboratory examinations were performed, and clinical data were collected. FMT was administered via frozen fecal microbial solution, and the fecal microbiota composition was analyzed using 16S rDNA sequencing before and after FMT.<br><br>RESULTS: The patient was diagnosed with IPEX syndrome with a mutation detected in the FOXP3 gene, which was identified as c.767T > C (p.M256T). He presented with recurrent watery diarrhea and respiratory infections after birth and developed a significant failure to thrive. Disturbances in the gut microbiota composition and marked decreased bacterial diversity were observed to be involved in the persistent and refractory diarrhea. After receiving FMT treatment, the patient responded with remission of the diarrhea without apparent side effects. His stool output significantly decreased, corresponding to increased microbial diversity and modification of his microbiota composition. The patient finally achieved full recovery after hematopoietic stem cell transplantation (HSCT).<br><br>CONCLUSION: Our data suggest an association between the gut microbiota and clinical symptoms of patient with IPEX syndrome and demonstrate FMT as an alternative therapy for severe diarrhea unresponsive to routine therapy in these patients.}, }
@article {pmid33356668, year = {2021}, author = {Settanni, CR and Bibbò, S and Ianiro, G and Rinninella, E and Cintoni, M and Mele, MC and Cammarota, G and Gasbarrini, A}, title = {Gastrointestinal involvement of autism spectrum disorder: focus on gut microbiota.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {15}, number = {6}, pages = {599-622}, doi = {10.1080/17474124.2021.1869938}, pmid = {33356668}, issn = {1747-4132}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Autism Spectrum Disorder/*complications/microbiology/physiopathology ; Combined Modality Therapy ; Diet Therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/complications/diagnosis/*microbiology/therapy ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Prebiotics ; Probiotics/pharmacology/therapeutic use ; }, abstract = {INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder typical of early age, characterized by impaired communication, social interaction, and repetitive behaviors. ASD patients frequently suffer from gastrointestinal (GI) symptoms. Neuro-psychological functions, intestinal homeostasis, and functional GI disturbances are modulated by the gut microbiota through the so-called 'microbiota-gut-brain axis'.<br><br>AREAS COVERED: Literature regarding GI symptoms among the ASD community as well as the involvement and modulation of the gut microbiota in GI disturbances of ASD patients was searched. Constipation, diarrhea, reflux, abdominal bloating, pain, and discomfort are reported with variable prevalence. ASD is characterized by a reduction of Bacteroidetes/Firmicutes, of the abundance of Bacteroidetes and other imbalances. ASD patients with GI symptoms present microbial changes with plausible relation with deficiency of digestive enzymes, carbohydrate malabsorption, selective eating, bacterial toxins, serotonin metabolism, and inflammation. The strategies to mitigate the GI distress through the gut microbiota modulation comprise antimicrobials, probiotics, prebiotics, fecal microbiota transplantation, and dietary intervention.<br><br>EXPERT OPINION: The modulation of the gut microbiota in ASD individuals with GI disturbances seems a promising target for the future medicine. A standardization of the research strategies for large-scale studies together with a focus on poorly explored fields is necessary to strengthen this hypothesis.}, }
@article {pmid33356449, year = {2022}, author = {Abbasi, A and Hajipour, N and Hasannezhad, P and Baghbanzadeh, A and Aghebati-Maleki, L}, title = {Potential in vivo delivery routes of postbiotics.}, journal = {Critical reviews in food science and nutrition}, volume = {62}, number = {12}, pages = {3345-3369}, doi = {10.1080/10408398.2020.1865260}, pmid = {33356449}, issn = {1549-7852}, mesh = {Insurance Benefits ; *Probiotics/administration &amp; dosage ; }, abstract = {Bioactive micro- and macro-molecules (postbiotics) derived from gut beneficial microbes are among natural chemical compounds with medical significance. Currently, a unique therapeutic strategy has been developed with an emphasis on the small molecular weight biomolecules that are made by the microbiome, which endow the host with several physiological health benefits. A large number of postbiotics have been characterized, which due to their unique pharmacokinetic properties in terms of controllable aspects of the dosage and various delivery routes, could be employed as promising medical tools since they exert both prevention and treatment strategies in the host. Nevertheless, there are still main challenges for the in vivo delivery of postbiotics. Currently, scientific literature confirms that targeted delivery systems based on nanoparticles, due to their appealing properties in terms of high biocompatibility, biodegradability, low toxicity, and significant capability to carry both hydrophobic and hydrophilic postbiotics, can be used as a novel and safe strategy for targeted delivery or/and release of postbiotics in various (oral, intradermal, and intravenous) in vivo models. The in vivo delivery of postbiotics are in their emerging phase and require massive investigation and randomized double-blind clinical trials if they are to be applied extensively as treatment strategies. This manuscript provides an overview of the various postbiotic metabolites derived from the gut beneficial microbes, their potential therapeutic activities, and recent progressions in the drug delivery field, as well as concisely giving an insight on the main in vivo delivery routes of postbiotics.}, }
@article {pmid33355397, year = {2020}, author = {Zueter, A}, title = {The status of cryptosporidiosis in Jordan: a review.}, journal = {Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit}, volume = {26}, number = {12}, pages = {1565-1569}, doi = {10.26719/emhj.20.065}, pmid = {33355397}, issn = {1687-1634}, mesh = {Child ; *Cryptosporidiosis/diagnosis/epidemiology ; *Cryptosporidium ; Diarrhea ; Feces ; Humans ; Jordan/epidemiology ; Prevalence ; }, abstract = {BACKGROUND: Cryptosporidium is a waterborne intestinal parasite that causes diarrhoea in low and middle-income countries worldwide. Reports from Mediterranean countries have documented the prevalence of cryptosporidiosis in children at various ages, also among cancer patients, and in cases of chronic kidney disease, haemodialysis, and organ transplant. Untill now, modified-acid staining preceded by stool concentration preparation remains the leading screening diagnostic test for the infection. In Jordan, few studies for cryptosporidiosis have been performed during the last 3 decades.<br><br>AIMS: This paper reviewed the status of cryptosporidiosis in Jordan and tracked recent updates for this emerging protozoal infection among different population groups.<br><br>METHODS: In this study, an online search was conducted on Google Scholar and PubMed databases using the keywords: Jordan, cryptosporidiosis and Cryptosporidium to inspect studies done on this parasite in Jordan.<br><br>RESULTS: Only 9 articles were identified from 1994 to 2019. These were analysed in terms of population group, demography, clinical history and the diagnostic tools used.<br><br>CONCLUSION: Cryptosporidiosis is still neglected in Jordan as indicated by the low number of studies over the last 3 decades and the prevalence is diverse depending on the diagnostic test used and socioeconomic status.}, }
@article {pmid33354044, year = {2020}, author = {Venkatachalam, B and Abraham, BK}, title = {Should We Fiddle with Gut Microbiome in Critically Ill?.}, journal = {Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine}, volume = {24}, number = {Suppl 4}, pages = {S211-S214}, pmid = {33354044}, issn = {0972-5229}, abstract = {The gut that we took for granted in the critically ill, as just a conduit for food passage has over the decade or so shown us that it is an active endocrine and exocrine organ with over 40 trillion microorganisms living commensally within it. This cosmos of microorganisms that is called the gut microbiome comprises roughly 1,000 different species and put together is more DNA than the entire human genome. Under normal circumstances, in a healthy individual multiple elements of the gut viz intestinal epithelium, gut barrier function, the microbiomes, all put together offer protection against infection and this is crucial in maintenance of health. Any change to the norm, be it in the form of surgical interventions, the introduction of medications, or the pathophysiological effects of systemic disease leads to a 360° alteration in this finely construed ecosystem leading to devastating effects that go beyond the boundaries of the gut itself. Intestinal epithelium helps to absorb nutrients as well as acts as the coordinator of mucosal immunity (first line of immune defense). During ill health, gut epithelial apoptosis occurs, alterations happen in the tight epithelial junctions leading to loss of gut barrier function and loss of the mucosal immunity leading to mucosal damage and hyperpermeability. Lastly, the microbiome is transformed into a pathobiome, with resultant increase in pathogenic bacteria and induction of virulence in commensal gut bacteria. Multiple organ damage starts to set in, caused by toxins leaving the intestine via both portal blood flow and mesenteric lymph. This review article traces the gut microbiomic ecology in health and sickness, modern tools that are used to manipulate gut microbiome in the search for the prevention and treatment of critical illness and will explore if appropriate manipulation of gut microbiome can influence or modulate the course of critical illness. How to cite this article: Venkatachalam B, Abraham BK. Should We Fiddle with Gut Microbiome in Critically Ill? Indian J Crit Care Med 2020;24(Suppl 4):S211-S214.}, }
@article {pmid33351150, year = {2021}, author = {Katayama, Y and Sugama, J and Suzuki, T and Ishimura, Y and Kobayashi, A and Moritoh, Y and Watanabe, M}, title = {Enteropeptidase inhibitor SCO-792 effectively prevents kidney function decline and fibrosis in a rat model of chronic kidney disease.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {36}, number = {4}, pages = {631-640}, pmid = {33351150}, issn = {1460-2385}, mesh = {Albuminuria/*drug therapy/etiology/pathology ; Animals ; Enteropeptidase/*antagonists &amp; inhibitors ; Enzyme Inhibitors/*pharmacology ; Fibrosis/*drug therapy/etiology/pathology ; Glomerular Filtration Rate ; Hypercholesterolemia/*physiopathology ; Kidney Diseases/*drug therapy/etiology/pathology ; Male ; Rats ; Renal Insufficiency, Chronic/*complications ; }, abstract = {BACKGROUND: Inhibiting enteropeptidase, a gut serine protease regulating protein digestion, suppresses food intake and ameliorates obesity and diabetes in mice. However, the effects of enteropeptidase inhibition on kidney parameters are largely unknown. Here, we evaluated the chronic effects of an enteropeptidase inhibitor, SCO-792, on kidney function, albuminuria and kidney pathology in spontaneously hypercholesterolaemic (SHC) rats, a rat chronic kidney disease (CKD) model.<br><br>METHODS: SCO-792, an orally available enteropeptidase inhibitor, was administered [0.03% and 0.06% (w/w) in the diet] to 20-week-old SHC rats showing albuminuria and progressive decline in glomerular filtration rate (GFR) for five weeks. The effects of SCO-792 and the contribution of amino acids to these effects were evaluated.<br><br>RESULTS: SCO-792 increased the faecal protein content, indicating that SCO-792 inhibited enteropeptidase in SHC rats. Chronic treatment with SCO-792 prevented GFR decline and suppressed albuminuria. Moreover, SCO-792 improved glomerulosclerosis and kidney fibrosis. Pair feeding with SCO-792 (0.06%) was less effective in preventing GFR decline, albuminuria and renal histological damage than SCO-792 treatment, indicating the enteropeptidase-inhibition-dependent therapeutic effects of SCO-792. SCO-792 did not affect the renal plasma flow, suggesting that its effect on GFR was mediated by an improvement in filtration fraction. Moreover, SCO-792 increased hydrogen sulphide production capacity, which has a role in tissue protection. Finally, methionine and cysteine supplementation to the diet abrogated SCO-792-induced therapeutic effects on albuminuria.<br><br>CONCLUSIONS: SCO-792-mediated inhibition of enteropeptidase potently prevented GFR decline, albuminuria and kidney fibrosis; hence, it may have therapeutic potential against CKD.}, }
@article {pmid33350700, year = {2021}, author = {Rosenberg, K}, title = {Fecal Microbiota Transplantation is Safe and Effective for C. Difficile Infection.}, journal = {The American journal of nursing}, volume = {121}, number = {1}, pages = {56}, doi = {10.1097/01.NAJ.0000731676.97290.c0}, pmid = {33350700}, issn = {1538-7488}, abstract = {According to this study: In standard clinical practice, fecal microbiota transplantation has a high success rate in patients with refractory Clostridioides difficile infection. In most cases, cure can be achieved with only one treatment.}, }
@article {pmid33350360, year = {2021}, author = {Holster, S and Repsilber, D and Geng, D and Hyötyläinen, T and Salonen, A and Lindqvist, CM and Rajan, SK and de Vos, WM and Brummer, RJ and König, J}, title = {Correlations between microbiota and metabolites after faecal microbiota transfer in irritable bowel syndrome.}, journal = {Beneficial microbes}, volume = {12}, number = {1}, pages = {17-30}, doi = {10.3920/BM2020.0010}, pmid = {33350360}, issn = {1876-2891}, mesh = {Bacteria/classification/genetics/isolation &amp; purification/*metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*metabolism/microbiology/*therapy ; Phylogeny ; Treatment Outcome ; }, abstract = {Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.}, }
@article {pmid33349199, year = {2021}, author = {Allocca, M and Filippi, E and Costantino, A and Bonovas, S and Fiorino, G and Furfaro, F and Peyrin-Biroulet, L and Fraquelli, M and Caprioli, F and Danese, S}, title = {Milan ultrasound criteria are accurate in assessing disease activity in ulcerative colitis: external validation.}, journal = {United European gastroenterology journal}, volume = {9}, number = {4}, pages = {438-442}, pmid = {33349199}, issn = {2050-6414}, mesh = {Adult ; Area Under Curve ; Biomarkers/analysis ; Colitis, Ulcerative/*diagnostic imaging ; Colon/*diagnostic imaging ; Colonoscopy ; Feces/chemistry ; Humans ; Intestinal Mucosa/diagnostic imaging ; Leukocyte L1 Antigen Complex/analysis ; Prospective Studies ; Sensitivity and Specificity ; Ultrasonography ; }, abstract = {INTRODUCTION: The aim of this study was to provide an external validation of bowel ultrasound (US) predictors of activity in ulcerative colitis (UC) and quantitative Milan Ultrasound Criteria (MUC).<br><br>METHODS: Forty-three consecutive patients with UC (16 in endoscopic remission and 27 with endoscopic activity) underwent bowel US and colonoscopy in a tertiary referral inflammatory bowel disease unit.<br><br>RESULTS: An MUC score >6.2 discriminated patients with active versus non-active UC with a sensitivity of 0.85 (95% confidence interval (CI) 0.66-0.96), specificity of 0.94 (95% CI 0.70-0.99) and an area under the curve of 0.902 (95% CI 0.772-0.971) in complete agreement with the derivation study.<br><br>CONCLUSION: The external validation of MUC confirms that it is an accurate tool for assessing disease activity in patients with UC.}, }
@article {pmid33348596, year = {2020}, author = {Neamah, WH and Busbee, PB and Alghetaa, H and Abdulla, OA and Nagarkatti, M and Nagarkatti, P}, title = {AhR Activation Leads to Alterations in the Gut Microbiome with Consequent Effect on Induction of Myeloid Derived Suppressor Cells in a CXCR2-Dependent Manner.}, journal = {International journal of molecular sciences}, volume = {21}, number = {24}, pages = {}, pmid = {33348596}, issn = {1422-0067}, support = {P20 GM103641/GM/NIGMS NIH HHS/United States ; R01 AI123947/AI/NIAID NIH HHS/United States ; R01 ES030144/ES/NIEHS NIH HHS/United States ; R01ES019313, R01MH094755, R01AI123947, R01AI129788, P01AT003961, P20GM103641, R01AT006888/NH/NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Basic Helix-Loop-Helix Transcription Factors/*metabolism ; Cells, Cultured ; DNA, Bacterial/genetics ; Dysbiosis/*chemically induced ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Mice ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells/*metabolism ; Phylogeny ; Polychlorinated Dibenzodioxins/*adverse effects ; Receptors, Aryl Hydrocarbon/*metabolism ; Receptors, Interleukin-8B/*metabolism ; Signal Transduction/*drug effects ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR and a known carcinogen. While AhR activation by TCDD leads to significant immunosuppression, how this translates into carcinogenic signal is unclear. Recently, we demonstrated that activation of AhR by TCDD in naïve C57BL6 mice leads to massive induction of myeloid derived-suppressor cells (MDSCs). In the current study, we investigated the role of the gut microbiota in TCDD-mediated MDSC induction. TCDD caused significant alterations in the gut microbiome, such as increases in Prevotella and Lactobacillus, while decreasing Sutterella and Bacteroides. Fecal transplants from TCDD-treated donor mice into antibiotic-treated mice induced MDSCs and increased regulatory T-cells (Tregs). Injecting TCDD directly into antibiotic-treated mice also induced MDSCs, although to a lesser extent. These data suggested that TCDD-induced dysbiosis plays a critical role in MDSC induction. Interestingly, treatment with TCDD led to induction of MDSCs in the colon and undetectable levels of cysteine. MDSCs suppressed T cell proliferation while reconstitution with cysteine restored this response. Lastly, blocking CXC chemokine receptor 2 (CXCR2) impeded TCDD-mediated MDSC induction. Our data demonstrate that AhR activation by TCDD triggers dysbiosis which, in turn, regulates, at least in part, induction of MDSCs.}, }
@article {pmid33347905, year = {2021}, author = {Rachid, R and Stephen-Victor, E and Chatila, TA}, title = {The microbial origins of food allergy.}, journal = {The Journal of allergy and clinical immunology}, volume = {147}, number = {3}, pages = {808-813}, pmid = {33347905}, issn = {1097-6825}, support = {R01 AI126915/AI/NIAID NIH HHS/United States ; R21 AI132843/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Dysbiosis/*immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Food Hypersensitivity/*immunology/microbiology/therapy ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunity, Mucosal ; Immunoglobulin A/metabolism ; Immunoglobulin E/metabolism ; *Models, Immunological ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Food allergy (FA) is a significant public health issue, propelled by its rapidly increasing prevalence. Its sharp rise into prominence has focused attention on causative environmental factors and their interplay with the immune system in disease pathogenesis. In that regard, there is now substantial evidence that alterations in the gut microbiome early in life imprint the host gut mucosal immunity and may play a critical role in precipitating FA. These changes may impact key steps in the development of the infant gut microbiome, including its shaping by maternal factors and upon the introduction of solid food (the weaning reaction). These early-life changes may have long-range effects on host immunity that manifest later in time as disease pathology. Experimental studies have shown that resetting the host intestinal immune responses by treatment with either a healthy fecal microbiota transplantation or defined commensal bacterial taxa can prevent or treat FA. The mechanisms by which these interventions suppress FA include restoration of gut immune regulatory checkpoints, notably the retinoic orphan receptor gamma T[+] regulatory T cells, the epithelial barrier, and healthy immunoglobulin A responses to the gut commensals. These findings inform human studies currently in progress that evaluate the role of microbial therapies in FA.}, }
@article {pmid33347881, year = {2021}, author = {Iliev, ID and Cadwell, K}, title = {Effects of Intestinal Fungi and Viruses on Immune Responses and Inflammatory Bowel Diseases.}, journal = {Gastroenterology}, volume = {160}, number = {4}, pages = {1050-1066}, pmid = {33347881}, issn = {1528-0012}, support = {UL1 TR001445/TR/NCATS NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; R01 DK093668/DK/NIDDK NIH HHS/United States ; R01 HL125816/HL/NHLBI NIH HHS/United States ; R01 AI140754/AI/NIAID NIH HHS/United States ; R01 AI130945/AI/NIAID NIH HHS/United States ; R01 AI121244/AI/NIAID NIH HHS/United States ; R56 AI137157/AI/NIAID NIH HHS/United States ; R01 DK121977/DK/NIDDK NIH HHS/United States ; R21 AI146957/AI/NIAID NIH HHS/United States ; R01 DK113136/DK/NIDDK NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; COVID-19/complications ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Immunity/*immunology ; Inflammatory Bowel Diseases/*etiology ; Lectins, C-Type/physiology ; Mycobiome/*physiology ; SARS-CoV-2 ; Th1 Cells/immunology ; Virome/*physiology ; }, abstract = {The intestinal microbiota comprises diverse fungal and viral components, in addition to bacteria. These microbes interact with the immune system and affect human physiology. Advances in metagenomics have associated inflammatory and autoimmune diseases with alterations in fungal and viral species in the gut. Studies of animal models have found that commensal fungi and viruses can activate host-protective immune pathways related to epithelial barrier integrity, but can also induce reactions that contribute to events associated with inflammatory bowel disease. Changes in our environment associated with modernization and the COVID-19 pandemic have exposed humans to new fungi and viruses, with unknown consequences. We review the lessons learned from studies of animal viruses and fungi commonly detected in the human gut and how these might affect health and intestinal disease.}, }
@article {pmid33346848, year = {2020}, author = {Leong, KSW and Jayasinghe, TN and Wilson, BC and Derraik, JGB and Albert, BB and Chiavaroli, V and Svirskis, DM and Beck, KL and Conlon, CA and Jiang, Y and Schierding, W and Vatanen, T and Holland, DJ and O'Sullivan, JM and Cutfield, WS}, title = {Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial.}, journal = {JAMA network open}, volume = {3}, number = {12}, pages = {e2030415}, pmid = {33346848}, issn = {2574-3805}, mesh = {Adolescent ; Body Mass Index ; Double-Blind Method ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Monitoring, Physiologic/methods ; New Zealand ; *Pediatric Obesity/metabolism/physiopathology/psychology/therapy ; *Quality of Life ; Treatment Outcome ; }, abstract = {IMPORTANCE: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation.<br><br>OBJECTIVE: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism.<br><br>This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020.<br><br>INTERVENTIONS: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo.<br><br>MAIN OUTCOMES AND MEASURES: Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition.<br><br>RESULTS: Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P&#x2009;=&#x2009;.007). There were no serious adverse events recorded throughout the trial.<br><br>CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits.<br><br>TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.}, }
@article {pmid33346444, year = {2020}, author = {Goloshchapov, OV and Chukhlovin, AB and Bakin, EA and Stanevich, OV and Klementeva, RV and Shcherbakov, AA and Shvetsov, AN and Suvorova, MA and Bondarenko, SN and Kucher, MA and Kulagin, AD and Zubarovskaya, LS and Moiseev, IS}, title = {[Fecal microbiota transplantation for graft-versus-host disease in children and adults: methods, clinical effects, safety].}, journal = {Terapevticheskii arkhiv}, volume = {92}, number = {7}, pages = {43-54}, doi = {10.26442/00403660.2020.07.000773}, pmid = {33346444}, issn = {0040-3660}, mesh = {Adult ; Child ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Prospective Studies ; Treatment Outcome ; }, abstract = {AIM: Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD).<br><br>MATERIALS AND METHODS: The prospective single-center study in R.M. Gorbacheva institute included 27 patients with GI GVHD after allogeneic stem cell transplantation. 19 patients received FMT, 8 patients received placebo. Clinical scales for GI autoimmune diseases were used to evaluate response. Microbiome alterations were assessed with multiplex PCR.<br><br>RESULTS: After FMT higher overall bacterial mass (&#x440;=0.00088), higher bacterial numbers ofBifidobacteriumspp. (&#x440;=0.021),Escherichia coli(&#x440;=0.049) andBacteroides fragilisgr. (&#x440;=0.000043) compared to placebo group. Also higher bacterial mass was observed in patients with clinical response (&#x440;=0.0057). The bacterial mass after procedure in non-responders was compared to the placebo group (&#x440;=0.31). Partial response of GVHD was achieved faster in the FMT group compared to placebo (median 4 days vs 48 days,p=0.014). Complete response was observed in 8 (42%), 14 (74%) and 16 (84%) at 30, 60 and 90 days respectively, while in the placebo group only 0%, 1 (13%) and 4 (50%) achieved complete response at the same time points. The incidence and severity of adverse events was comparable between FMT and the placebo group.<br><br>CONCLUSION: FMT in patients with refractory GI GVHD was associated with favorable clinical outcomes and recovery in certain marker bacterial populations. Multiplex PCR can be used to assess an engraftment of a donor microbiota. FMT in GI GVHD was not associated with life-threatening adverse events, but further studies are required to validate clinical efficacy.}, }
@article {pmid33345703, year = {2020}, author = {Green, JE and Davis, JA and Berk, M and Hair, C and Loughman, A and Castle, D and Athan, E and Nierenberg, AA and Cryan, JF and Jacka, F and Marx, W}, title = {Efficacy and safety of fecal microbiota transplantation for the treatment of diseases other than Clostridium difficile infection: a systematic review and meta-analysis.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1-25}, pmid = {33345703}, issn = {1949-0984}, mesh = {Colitis, Ulcerative/*therapy ; Drug Resistance, Bacterial/genetics ; Fecal Microbiota Transplantation/adverse effects/*methods ; Gastrointestinal Microbiome/physiology ; Humans ; Irritable Bowel Syndrome/*therapy ; Liver Diseases/*therapy ; Metabolic Syndrome/*therapy ; Obesity/*therapy ; Treatment Outcome ; }, abstract = {The intestinal microbiome has been identified as a key modifier for a variety of health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a fast, safe, and effective means by which to modify the intestinal microbiome and potentially treat a variety of health conditions. Despite extensive research of FMT for CDI, there is a lack of clarity informed by systematic synthesis of data regarding the safety and efficacy of FMT for other health conditions. This systematic review used PRISMA guidelines and was prospectively registered with PROSPERO (CRD42018104243). In March 2020, a search of MEDLINE, EMBASE, and PsycINFO was conducted. We identified 26 eligible studies. A meta-analysis of FMT for active Ulcerative Colitis (UC) showed that FMT significantly improved rates of clinical remission (OR = 3.634, 95% CI = 1.940 to 6.808, I[2] = 0%, p < .001), clinical response (OR = 2.634, 95% CI = 1.441 to 4.815, I[2] = 33%, p = .002) and endoscopic remission (OR = 4.431, 95% CI = 1.901 to 10.324, I[2] = 0%, p = .001). With respect to Irritable Bowel Syndrome, a meta-analysis showed no significant change in symptoms following FMT (p = .739). Hepatic disorders, metabolic syndrome, and antibiotic-resistant organisms were conditions with emerging data on FMT. Serious adverse events (AE) were more often reported in control group participants (n = 43) compared with FMT group participants (n = 26). There were similar rates of mild to moderate AE in both groups. Preliminary data suggest that FMT is a potentially safe, well-tolerated and efficacious treatment for certain conditions other than CDI, with evidence for active UC being the most compelling.}, }
@article {pmid33342544, year = {2021}, author = {Needham, BD and Adame, MD and Serena, G and Rose, DR and Preston, GM and Conrad, MC and Campbell, AS and Donabedian, DH and Fasano, A and Ashwood, P and Mazmanian, SK}, title = {Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder.}, journal = {Biological psychiatry}, volume = {89}, number = {5}, pages = {451-462}, pmid = {33342544}, issn = {1873-2402}, support = {R01 HD090214/HD/NICHD NIH HHS/United States ; R01 MH100556/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; *Autism Spectrum Disorder ; Feces ; *Gastrointestinal Microbiome ; Mice ; Pilot Projects ; Plasma ; }, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal dysfunction, and altered gut microbiome compositions.<br><br>METHODS: We sought to better understand nonbehavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (ultrahigh performance liquid chromatography-tandem mass spectrometry) with broad panels of identified metabolites. Herein, we compared the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing control children.<br><br>RESULTS: Differences in amino acid, lipid, and xenobiotic metabolism distinguished ASD and typically developing samples. Our results implicated oxidative stress and mitochondrial dysfunction, hormone level elevations, lipid profile changes, and altered levels of phenolic microbial metabolites. We also revealed correlations between specific metabolite profiles and clinical behavior scores. Furthermore, a summary of metabolites modestly associated with gastrointestinal dysfunction in ASD is provided, and a pilot study of metabolites that can be transferred via fecal microbial transplant into mice is identified.<br><br>CONCLUSIONS: These findings support a connection between metabolism, gastrointestinal physiology, and complex behavioral traits and may advance discovery and development of molecular biomarkers for ASD.}, }
@article {pmid33339331, year = {2020}, author = {Łusiak-Szelachowska, M and Weber-Dąbrowska, B and Żaczek, M and Borysowski, J and Górski, A}, title = {The Presence of Bacteriophages in the Human Body: Good, Bad or Neutral?.}, journal = {Microorganisms}, volume = {8}, number = {12}, pages = {}, pmid = {33339331}, issn = {2076-2607}, support = {.//This work was supported by the statutory funds from the Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences./ ; }, abstract = {The presence of bacteriophages (phages) in the human body may impact bacterial microbiota and modulate immunity. The role of phages in human microbiome studies and diseases is poorly understood. However, the correlation between a greater abundance of phages in the gut in ulcerative colitis and diabetes has been suggested. Furthermore, most phages found at different sites in the human body are temperate, so their therapeutic effects and their potential beneficial effects remain unclear. Hence, far, no correlation has been observed between the presence of widespread crAssphage in the human population and human health and diseases. Here, we emphasize the beneficial effects of phage transfer in fecal microbiota transplantation (FMT) in Clostridioides difficile infection. The safety of phage use in gastrointestinal disorders has been demonstrated in clinical studies. The significance of phages in the FMT as well as in gastrointestinal disorders remains to be established. An explanation of the multifaceted role of endogenous phages for the development of phage therapy is required.}, }
@article {pmid33331810, year = {2021}, author = {Simmonds, P and Williams, S and Harvala, H}, title = {Understanding the outcomes of COVID-19 - does the current model of an acute respiratory infection really fit?.}, journal = {The Journal of general virology}, volume = {102}, number = {3}, pages = {}, pmid = {33331810}, issn = {1465-2099}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Antibodies, Viral/*immunology ; COVID-19/*immunology ; Hepatitis C/immunology ; Humans ; Immunity, Humoral ; Immunoglobulin G/immunology ; Influenza, Human/immunology ; Models, Biological ; Reinfection ; Respiratory Tract Infections/*immunology ; SARS-CoV-2/genetics/*immunology/isolation &amp; purification ; }, abstract = {Although coronavirus disease 2019 (COVID-19) is regarded as an acute, resolving infection followed by the development of protective immunity, recent systematic literature review documents evidence for often highly prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory and faecal samples, periodic recurrence of PCR positivity in a substantial proportion of individuals and increasingly documented instances of reinfection associated with a lack of protective immunity. This pattern of infection is quite distinct from the acute/resolving nature of other human pathogenic respiratory viruses, such as influenza A virus and respiratory syncytial virus. Prolonged shedding of SARS-CoV-2 furthermore occurs irrespective of disease severity or development of virus-neutralizing antibodies. SARS-CoV-2 possesses an intensely structured RNA genome, an attribute shared with other human and veterinary coronaviruses and with other mammalian RNA viruses such as hepatitis C virus. These are capable of long-term persistence, possibly through poorly understood RNA structure-mediated effects on innate and adaptive host immune responses. The assumption that resolution of COVID-19 and the appearance of anti-SARS-CoV-2 IgG antibodies represents virus clearance and protection from reinfection, implicit for example in the susceptible-infected-recovered (SIR) model used for epidemic prediction, should be rigorously re-evaluated.}, }
@article {pmid33331486, year = {2020}, author = {Terra, DAA and Vilela, EG and Silva, ROS and LeÃo, LA and Lima, KS and Passos, RIF&#xc2; and Diniz, AN and Coelho, LGV}, title = {STRUCTURING A FECAL MICROBIOTA TRANSPLANTATION CENTER IN A UNIVERSITY HOSPITAL IN BRAZIL.}, journal = {Arquivos de gastroenterologia}, volume = {57}, number = {4}, pages = {434-458}, doi = {10.1590/S0004-2803.202000000-79}, pmid = {33331486}, issn = {1678-4219}, mesh = {Brazil ; Clostridioides difficile ; Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC).<br><br>OBJECTIVE: The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection.<br><br>METHODS: The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects.<br><br>RESULTS: A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index &#x2265;25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%.<br><br>CONCLUSION: The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries.}, }
@article {pmid33330910, year = {2021}, author = {Gerardin, Y and Timberlake, S and Allegretti, JR and Smith, MB and Kassam, Z}, title = {Beyond Fecal Microbiota Transplantation: Developing Drugs from the Microbiome.}, journal = {The Journal of infectious diseases}, volume = {223}, number = {12 Suppl 2}, pages = {S276-S282}, doi = {10.1093/infdis/jiaa700}, pmid = {33330910}, issn = {1537-6613}, mesh = {Anti-Bacterial Agents/isolation &amp; purification/*therapeutic use ; Clostridioides difficile/drug effects ; Clostridium Infections/therapy ; Drug Development ; Drug Discovery ; Drug Resistance, Bacterial/drug effects ; *Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, abstract = {The transfer of live gut microbes may transform patient care across a range of autoimmune, metabolic, hepatic, and infectious diseases. One early approach, fecal microbiota transplantation, has shown promise in Clostridiodes difficile infection and the potential for improving clinical and public health outcomes for other antibiotic-resistant bacteria. These clinical successes have motivated the development of microbiome drugs, which will need to address challenges in safety, uniformity, and delivery while seeking to preserve the benefits of using whole microbiome communities as novel therapeutics and an innovative platform for drug discovery.}, }
@article {pmid33330900, year = {2021}, author = {Miller, WD and Keskey, R and Alverdy, JC}, title = {Sepsis and the Microbiome: A Vicious Cycle.}, journal = {The Journal of infectious diseases}, volume = {223}, number = {12 Suppl 2}, pages = {S264-S269}, pmid = {33330900}, issn = {1537-6613}, support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; T32 HL007605/HL/NHLBI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship ; Gastrointestinal Microbiome/drug effects/immunology ; Humans ; Immunity ; *Microbiota/drug effects/immunology ; Sepsis/drug therapy/immunology/*microbiology ; }, abstract = {Sepsis has been characterized as a dysregulated host response to infection, and the role of the microbiome as a key influencer of this response is emerging. Disruption of the microbiome while treating sepsis with antibiotics can itself result in immune dysregulation. Alterations in the gut microbiome resulting from sepsis and its treatment have been implicated in organ dysfunction typical of sepsis across multiple tissues including the lung, kidney, and brain. Multiple microbiota-directed interventions are currently under investigation in the setting of sepsis, including fecal transplant, the administration of dietary fiber, and the use of antibiotic scavengers that attenuate the effects of antibiotics on the gut microbiota while allowing them to concentrate at the primary sites of infection. The emerging evidence shows that the gut microbiome interacts with various elements of the septic response, and provides yet another reason to consider the judicious use of antibiotics via antibiotic stewardship programs.}, }
@article {pmid33329430, year = {2020}, author = {Liang, Q and Zhang, M and Hu, Y and Zhang, W and Zhu, P and Chen, Y and Xue, P and Li, Q and Wang, K}, title = {Gut Microbiome Contributes to Liver Fibrosis Impact on T Cell Receptor Immune Repertoire.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {571847}, pmid = {33329430}, issn = {1664-302X}, abstract = {Gut microbiota (GM) modifies the intrahepatic immune microenvironment, but the underlying mechanisms remain poorly understood. Liver fibrosis-associated imprinting is predicted to be reflected in GM. This study investigated the link between GM and the intrahepatic T cell receptor (TCR) immune repertoire (IR), and whether GM modulates the intrahepatic immune microenvironment via TCR IR during liver fibrosis. We analyzed the correlation between GM and TCR IR during liver fibrogenesis. Accordingly, 16S rRNA gene sequencing (16S-seq) and bulk immune repertoire sequencing (IR-seq) were performed to characterize GM and intrahepatic TCR IR. Fecal microbial transplant (FMT) and TCRβ knockout (Tcrb[KO]) mouse models were employed to determine the biological link between GM and TCR IR in liver fibrosis. We found that GM and intrahepatic TCR IR are highly correlated, with both showing reduced diversity and centralized distribution during liver fibrosis. The restoration of normal intestinal microbiota may reshape intrahepatic TCR IR and delay liver fibrosis. Interestingly, TCR IR ablation abrogated the impact of GM on liver fibrogenesis. Furthermore, GM modulated hepatic stellate cell (HSC) activation via TCR IR-mediated intrahepatic immune milieu. Our study demonstrates that GM, which exhibits cross-talk with the intrahepatic TCR IR, influences the intrahepatic immune microenvironment and liver fibrosis progression.}, }
@article {pmid33326127, year = {2021}, author = {Bilinski, J and Lis, K and Tomaszewska, A and Grzesiowski, P and Dzieciatkowski, T and Tyszka, M and Karakulska-Prystupiuk, E and Boguradzki, P and Tormanowska, M and Halaburda, K and Waszczuk-Gajda, A and Wiktor-Jedrzejczak, W and Basak, GW}, title = {Fecal microbiota transplantation in patients with acute and chronic graft-versus-host disease-spectrum of responses and safety profile. Results from a prospective, multicenter study.}, journal = {American journal of hematology}, volume = {96}, number = {3}, pages = {E88-E91}, doi = {10.1002/ajh.26077}, pmid = {33326127}, issn = {1096-8652}, mesh = {Adult ; Aged ; Allografts ; Caliciviridae Infections/etiology/transmission ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Graft vs Host Disease/etiology/microbiology/*therapy ; Hematologic Diseases/therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prospective Studies ; Sepsis/etiology ; Shock, Septic/etiology ; Treatment Outcome ; Young Adult ; }, }
@article {pmid33324357, year = {2020}, author = {Lee, KE and Kim, JK and Kim, DH}, title = {Orally Administered Antibiotics Vancomycin and Ampicillin Cause Cognitive Impairment With Gut Dysbiosis in Mice With Transient Global Forebrain Ischemia.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {564271}, pmid = {33324357}, issn = {1664-302X}, abstract = {Gut microbiota is closely associated with the occurrence of neuropsychiatric disorders. Antibiotics are frequently used to prevent pathogen infection in patients with brain ischemia. To understand the impact of prophylactic antibiotic treatment for patients with brain ischemia, we examined the effects of orally administered vancomycin and ampicillin on cognitive function and gut microbiota composition in mice with transient global forebrain ischemia (tIsc). tIsc operation and orally gavaged vancomycin mildly and moderately caused cognitive impairment, respectively. However, the exposure of mice with tIsc to vancomycin or ampicillin severely impaired cognitive function in the Y-maze, novel object recognition, and Banes maze tasks. Furthermore, their treatments induced NF-κB activation as well as active microglia (NF-κB[+]/Iba1[+] and LPS[+]/Iba1[+] cells) and apoptotic (caspase 3[+]/NeuN[+]) cell population in the hippocampus, whereas the brain-derived neurotrophic factor (BDNF)[+]/NeuN[+] cell populations decreased. These treatments also caused colitis and gut dysbiosis. They increased the population of Proteobacteria including Enterobacter xiangfangenesis. Orally delivered fecal transplantation of vancomycin-treated mice with or without tIsc and oral gavage of Enterobacter xiangfangenesis also significantly deteriorated the cognitive impairment and colitis in transplanted mice with tIsc. These findings suggest that oral administration of antibiotics can deteriorate cognitive impairment with gut dysbiosis in patients with brain ischemia.}, }
@article {pmid33321019, year = {2020}, author = {Leclercq, S and de Timary, P and Stärkel, P}, title = {Targeting the gut microbiota to treat alcoholic liver diseases: evidence and promises.}, journal = {Acta gastro-enterologica Belgica}, volume = {83}, number = {4}, pages = {616-621}, pmid = {33321019}, issn = {1784-3227}, mesh = {*Alcoholism ; Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Liver Diseases, Alcoholic/therapy ; *Probiotics/therapeutic use ; }, abstract = {The human intestine is colonized by a variety of microbes that influence the metabolic responses, the immune system and the nervous system. Dietary patterns are important factors that shape the composition of the gut microbiota. Many animal models of alcohol exposure have highlighted the key role of the alcohol-induced gut microbiota alterations, leaky gut and translocation of microbial products in the development of alcoholic liver disease (ALD). However, in humans, there is no clear picture defining an "alcoholic microbiome", and the link between intestinal dysbiosis and ALD development is far from being understood. Although we do not comprehend all the mechanistic insights, clinical studies aiming at modulating the gut microbiota of alcoholic patients have shown some beneficial effects. Here we review the potential therapeutic effects of probiotics in ALD and give some clinical perspectives on the role of prebiotics and the use of fecal microbiota transplantation.}, }
@article {pmid33318367, year = {2020}, author = {Raina, S}, title = {Neuromodulation for Restoration of Urinary and Bowel Control.}, journal = {Neurology India}, volume = {68}, number = {Supplement}, pages = {S307-S315}, doi = {10.4103/0028-3886.302457}, pmid = {33318367}, issn = {1998-4022}, mesh = {*Electric Stimulation Therapy ; Humans ; *Urinary Tract ; }, abstract = {Control of the lower urinary tract is a complex, multilevel process that involves the peripheral and central nervous systems. Patients with spinal cord diseases or injuries present with multiple bladder and bowel problems. The commonest are urinary, urgency, frequency, urge incontinence, retention and/or fecal incontinence. Though the first reports of neurostimulation to empty bladder came in 1970s', it was only in 1988 that Schmidt and Tanagho restarted discussion and application of neuromodulation and electrical stimulation of sacral nerve in urology. In April, 1999 - FDA approved the InterStim System for treatment of symptoms of urgency-frequency and urinary retention. In October 2000, Medtronic Commercial Release for SNS-Bowel was approved. In October 2002, the Tined lead was launched and N'Vision programmer was launched in the official market in Europe. SNM is now considered the third line of management in refractory cases of OAB, chronic NOUR, frequency and urgency. Role in neuropathic bladder is still being assessed. SNM includes a thorough preoperative assessment, PNE (Percutaneous Nerve Evaluation) without any muscle relaxation and finally installation of a permanent IPG after assessing reponse. We have an experience of over 20 patients in last 11 years. These include patients of refractory OAB, chronic NOUR and Cauda Equina Syndrome. We do a two-staged procedure in view of the high cost and abide by the AUA, EAU and ICS guidelines. Our long term results for neuropathic OAB are awaited.}, }
@article {pmid33317795, year = {2020}, author = {Morkūnas, E and Skiecevičienė, J and Kupčinskas, J}, title = {The impact of modulating the gastrointestinal microbiota in cancer patients.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {48-49}, number = {}, pages = {101700}, doi = {10.1016/j.bpg.2020.101700}, pmid = {33317795}, issn = {1532-1916}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Immunotherapy/*methods ; Neoplasms/*microbiology/therapy ; }, abstract = {Gastrointestinal microbiota is vastly deregulated in cancer patients due to different factors, but the exact mechanisms of interaction between cancer and microbiome are still poorly understood. Current evidence suggests that alterations in the composition of the microbiota may affect efficacy and toxicity of anti-cancer therapies. Recent preclinical and clinical studies demonstrate different mechanisms and outcomes of deregulation of gut microbiome, and investigate effects of modulating gastrointestinal microbiota in cancer patients. This paper reviews effects of altered microbiome on anti-cancer management, including antibiotics, chemotherapy and immunotherapy, as well as possible outcomes of modulating altered microbiome by probiotics or faecal microbiome transplantation in cancer patients.}, }
@article {pmid33317787, year = {2020}, author = {Cheung, VTF and Brain, O}, title = {Immunotherapy induced enterocolitis and gastritis - What to do and when?.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {48-49}, number = {}, pages = {101703}, doi = {10.1016/j.bpg.2020.101703}, pmid = {33317787}, issn = {1532-1916}, mesh = {Enterocolitis/*chemically induced ; Gastritis/*chemically induced ; Humans ; Immune Checkpoint Inhibitors/*adverse effects/pharmacology ; Immunotherapy/*adverse effects ; Prospective Studies ; }, abstract = {Oncological treatment has been revolutionised by the advent of immune checkpoint inhibitors (ICPi), which block inhibitory immune pathways to enhance anti-tumour responses and improve survival. This mode of action is non-specific so can cause immune-related adverse events, of which diarrhoea and enterocolitis are amongst the most common. ICPi-enterocolitis frequently leads to cancer therapy interruption. ICPi-gastritis typically occurs at a later stage of ICPi therapy and can present more insidiously with nausea and vomiting. ICPi-enterocolitis and gastritis are treated with corticosteroids, with refractory cases typically requiring biologic therapy. This review will briefly consider the pathogenesis of ICPi-induced GI disease, before focussing on the practical management of these conditions. The anticipated global increase in ICPi use across cancer types highlights the importance of prospective research in order that we can understand the immuno-microbiology of ICPi-enterocolitis and gastritis. This will lead to predictive biomarkers and help to define optimal treatment regimens.}, }
@article {pmid33317136, year = {2020}, author = {Wirth, U and Garzetti, D and Jochum, LM and Spriewald, S and Kühn, F and Ilmer, M and Lee, SML and Niess, H and Bazhin, AV and Andrassy, J and Werner, J and Stecher, B and Schiergens, TS}, title = {Microbiome Analysis from Paired Mucosal and Fecal Samples of a Colorectal Cancer Biobank.}, journal = {Cancers}, volume = {12}, number = {12}, pages = {}, pmid = {33317136}, issn = {2072-6694}, support = {to B.S.//Deutsches Zentrum f&#xfc;r Infektionsforschung/ ; }, abstract = {The role of gut microbiota in colorectal cancer is subject to extensive research. Before usage of biorepositories for microbiome studies, it is crucial to evaluate technical feasibility of microbiome profiling from various biospecimens. The aim of this study was to assess the feasibility of DNA-extraction and microbiome profiling of samples from different sample sites, tissue sites and storage duration of a colorectal cancer biobank. Mucosa samples, mucosal scrapings and feces as well as different tissue sites (tumor, normal mucosa) were analyzed. 16S rRNA gene-based microbiome profiling with taxonomic assignment was performed on the Illumina MiSeq (Illumina, San Diego, USA) platform from stored snap frozen samples. For statistical analysis, α- and β-diversity measures, PCoA, permutational multivariate analysis of variance and graphical representation were performed. Microbiome analysis could be successfully performed in most of the samples (overall 93.3%) with sufficient numbers of high-quality reads. There were no differences between sample sites, while in some measures significant differences were found between tumor and normal mucosa (α-diversity, Shannon/Simpson Indices p = 0.028/0.027, respectively). Samples stored for up to eight years were used and storage conditions had no significant influence on the results. Tumor and tissue samples of a biobank stored long term can be successfully used for microbiome analysis. As large sample sizes are needed for association studies to evaluate microbial impact on tumorigenesis or progression of colorectal cancer, an already established biorepository may be a useful alternative to prospective clinical studies.}, }
@article {pmid33311550, year = {2020}, author = {Aluthge, ND and Tom, WA and Bartenslager, AC and Burkey, TE and Miller, PS and Heath, KD and Kreikemeier-Bower, C and Kittana, H and Schmaltz, RJ and Ramer-Tait, AE and Fernando, SC}, title = {Differential longitudinal establishment of human fecal bacterial communities in germ-free porcine and murine models.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {760}, pmid = {33311550}, issn = {2399-3642}, mesh = {Animals ; Bacteria/classification/genetics ; Biodiversity ; Computational Biology/methods ; Disease Models, Animal ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Metagenome ; Metagenomics/methods ; Mice ; Phylogeny ; Reproducibility of Results ; }, abstract = {The majority of microbiome studies focused on understanding mechanistic relationships between the host and the microbiota have used mice and other rodents as the model of choice. However, the domestic pig is a relevant model that is currently underutilized for human microbiome investigations. In this study, we performed a direct comparison of the engraftment of fecal bacterial communities from human donors between human microbiota-associated (HMA) piglet and mouse models under identical dietary conditions. Analysis of 16S rRNA genes using amplicon sequence variants (ASVs) revealed that with the exception of early microbiota from infants, the more mature microbiotas tested established better in the HMA piglets compared to HMA mice. Of interest was the greater transplantation success of members belonging to phylum Firmicutes in the HMA piglets compared to the HMA mice. Together, these results provide evidence for the HMA piglet model potentially being more broadly applicable for donors with more mature microbiotas while the HMA mouse model might be more relevant for developing microbiotas such as those of infants. This study also emphasizes the necessity to exercise caution in extrapolating findings from HMA animals to humans, since up to 28% of taxa from some donors failed to colonize either model.}, }
@article {pmid33311466, year = {2020}, author = {Chevalier, G and Siopi, E and Guenin-Macé, L and Pascal, M and Laval, T and Rifflet, A and Boneca, IG and Demangel, C and Colsch, B and Pruvost, A and Chu-Van, E and Messager, A and Leulier, F and Lepousez, G and Eberl, G and Lledo, PM}, title = {Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6363}, pmid = {33311466}, issn = {2041-1723}, mesh = {Animals ; *Behavior, Animal ; Depression/*complications ; Disease Models, Animal ; Endocannabinoids/*pharmacology ; Fatty Acids/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Lactobacillus/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Neurogenesis/drug effects ; Stress, Psychological/*complications ; }, abstract = {Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that UCMS mice display phenotypic alterations, which could be transferred from UCMS donors to naïve recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota were alleviated by selectively enhancing the central eCB or by complementation with a strain of the Lactobacilli genus. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system.}, }
@article {pmid33310084, year = {2021}, author = {Galipeau, HJ and Caminero, A and Turpin, W and Bermudez-Brito, M and Santiago, A and Libertucci, J and Constante, M and Raygoza Garay, JA and Rueda, G and Armstrong, S and Clarizio, A and Smith, MI and Surette, MG and Bercik, P and ,  and Croitoru, K and Verdu, EF}, title = {Novel Fecal Biomarkers That Precede Clinical Diagnosis of Ulcerative Colitis.}, journal = {Gastroenterology}, volume = {160}, number = {5}, pages = {1532-1545}, doi = {10.1053/j.gastro.2020.12.004}, pmid = {33310084}, issn = {1528-0012}, support = {143253//CIHR/Canada ; 1715-000-001//CIHR/Canada ; }, mesh = {Adolescent ; Adult ; Animals ; Bacteria/drug effects/*enzymology/genetics ; Bacterial Proteins/genetics/*metabolism ; Biomarkers/metabolism ; Case-Control Studies ; Child ; Colitis, Ulcerative/diagnosis/drug therapy/*microbiology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome/drug effects ; Germ-Free Life ; Humans ; Male ; Metagenome ; Metagenomics ; Mice, Inbred C57BL ; Peptide Hydrolases/genetics/*metabolism ; Predictive Value of Tests ; Prospective Studies ; Protease Inhibitors/therapeutic use ; Proteolysis ; Reproducibility of Results ; Ribotyping ; Young Adult ; Mice ; }, abstract = {BACKGROUND &amp; AIMS: Altered gut microbiota composition and function have been associated with inflammatory bowel diseases, including ulcerative colitis (UC), but the causality and mechanisms remain unknown.<br><br>METHODS: We applied 16S ribosomal RNA gene sequencing, shotgun metagenomic sequencing, in&#xa0;vitro functional assays, and gnotobiotic colonizations to define the microbial composition and function in fecal samples obtained from a cohort of healthy individuals at risk for inflammatory bowel diseases (pre-UC) who later developed UC (post-UC) and matched healthy control individuals (HCs).<br><br>RESULTS: Microbiota composition of post-UC samples was different from HC and pre-UC samples; however, functional analysis showed increased fecal proteolytic and elastase activity before UC onset. Metagenomics identified more than 22,000 gene families that were significantly different between HC, pre-UC, and post-UC samples. Of these, 237 related to proteases and peptidases, suggesting a bacterial component to the pre-UC proteolytic signature. Elastase activity inversely correlated with the relative abundance of Adlercreutzia and other potentially beneficial taxa and directly correlated with known proteolytic taxa, such as Bacteroides vulgatus. High elastase activity was confirmed in Bacteroides isolates from fecal samples. The bacterial contribution and functional significance of the proteolytic signature were investigated in germ-free adult mice and in dams colonized with HC, pre-UC, or post-UC microbiota. Mice colonized with or born from pre-UC-colonized dams developed higher fecal proteolytic activity and an inflammatory immune tone compared with HC-colonized mice.<br><br>CONCLUSIONS: We have identified increased fecal proteolytic activity that precedes the clinical diagnosis of UC and associates with gut microbiota changes. This proteolytic signature may constitute a noninvasive biomarker of inflammation to monitor at-risk populations that can be targeted therapeutically with antiproteases.}, }
@article {pmid33309513, year = {2021}, author = {Knudsen, MD and Botteri, E and Holme, &#xd8; and Hjartåker, A and Song, M and Thiis-Evensen, E and Norvard, ER and Schult, AL and Randel, KR and Hoff, G and Berstad, P}, title = {Association between lifestyle and site-specific advanced colorectal lesions in screening with faecal immunochemical test and sigmoidoscopy.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {53}, number = {3}, pages = {353-359}, doi = {10.1016/j.dld.2020.11.021}, pmid = {33309513}, issn = {1878-3562}, mesh = {Aged ; Alcohol Drinking/epidemiology ; Biomarkers, Tumor/analysis ; Colorectal Neoplasms/*diagnosis ; Female ; Humans ; *Life Style ; Male ; Middle Aged ; Obesity/epidemiology ; *Occult Blood ; Referral and Consultation/statistics &amp; numerical data ; Sigmoidoscopy/*statistics &amp; numerical data ; Smoking/epidemiology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Lifestyle factors may help to identify individuals at high-risk for colorectal cancer (CRC).<br><br>AIMS: To examine the association between lifestyle, referral for follow-up colonoscopy and proximal neoplasia detection in CRC screening.<br><br>METHODS: In this observational study, 14,832 individuals aged 50-74 years were invited to faecal immunochemical test (FIT) or sigmoidoscopy screening. Advanced lesions (AL), including advanced adenomas, advanced serrated lesions&#xa0;and CRC were divided according to location: distal-only, or proximal with or without distal AL. We collected information on smoking habit, body mass index and alcohol intake through a questionnaire.<br><br>RESULTS: Out of 3,318 FIT and 2,988 sigmoidoscopy participants, 516 (16%) and 338 (11%), respectively, were referred for follow-up colonoscopy after a positive screening test. Two-hundred-and-fifty-six (4%) had distal-only and 119 (2%) proximal AL. In FIT participants, obesity and high alcohol intake were associated with proximal AL; odds ratio (95% confidence interval) 2.68 (1.36-5.26) and 2.16 (1.08-4.30), respectively. In sigmoidoscopy participants, current smoking was associated with proximal AL; 4.58 (2.24-9.38), and current smoking and obesity were associated with referral for colonoscopy; 2.80 (2.02-3.89) and 1.42 (1.01-2.00), respectively.<br><br>CONCLUSION: Current smoking, obesity and high alcohol intake were associated with screen-detected proximal colorectal AL. Current smoking and obesity were associated with referral for follow-up colonoscopy in sigmoidoscopy screening.}, }
@article {pmid33309073, year = {2021}, author = {Aràjol, C and Aira Gómez, A and González-Suárez, B and Casals-Pascual, C and Martí Martí, S and Domínguez Luzón, M&#xc1; and Soriano, A and Guardiola Capón, J and , }, title = {Donor selection for faecal microbiota transplantation. Consensus document of the Catalan Society of Gastroenterology and the Catalan Society of Infectious Diseases and Clinical Microbiology.}, journal = {Gastroenterologia y hepatologia}, volume = {44}, number = {2}, pages = {175-180}, doi = {10.1016/j.gastrohep.2020.07.027}, pmid = {33309073}, issn = {0210-5705}, mesh = {Donor Selection/*standards ; *Fecal Microbiota Transplantation ; Humans ; }, abstract = {Faecal microbiota transplantation (FMT) is an effective and safe treatment of recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the faecal microbiota donor is a key part of the process to ensure recipient safety. Protocols of action must be implemented that allow clinicians to act with the maximum guarantees and to minimise the risks of the procedure. In this regard, a multidisciplinary working group has been set up with the aim of establishing recommendations for selecting the faecal microbiota donor.}, }
@article {pmid33307184, year = {2022}, author = {Dawwas, GK and Brensinger, CM and Vajravelu, RK and Wu, Q and Kelly, CR and Laine, L and Wu, GD and Lewis, JD}, title = {Long-term Outcomes Following Multiply Recurrent Clostridioides difficile Infection and Fecal Microbiota Transplantation.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {20}, number = {4}, pages = {806-816.e6}, pmid = {33307184}, issn = {1542-7714}, support = {R24 AI118629/AI/NIAID NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {*Clostridioides difficile ; *Clostridium Infections/complications/therapy ; Fecal Microbiota Transplantation/adverse effects ; Humans ; Recurrence ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is a commonly used therapy for multiply recurrent Clostridioides difficile (mrCDI). By altering the gut microbiota, there is the potential for FMT to impact the risk for cardiometabolic, intestinal or immune-mediated conditions. Likewise, the microbiota disturbance associated with mrCDI could potentially lead to these conditions. We aimed to assess the associations of mrCDI and FMT with cardiometabolic, immune-mediated diseases, and irritable bowel syndrome.<br><br>METHODS: This retrospective cohort study using a United States commercial claims database included persons diagnosed with CDI or undergoing FMT. We created 2 pairwise comparisons: mrCDI vs non-mrCDI, and non-mrCDI or mrCDI treated with FMT vs mrCDI without FMT.<br><br>RESULTS: We found no significant association between mrCDI (vs non-mrCDI) and inflammatory bowel disease (adjusted hazard ratio (aHR) = 1.65; 95% confidence interval, 0.67-4.04), rheumatoid arthritis (HR = 0.86; 0.47-1.56), psoriasis (HR = 0.72; 0.23-2.27), diabetes (aHR = 0.97; 0.67-1.40), hypertension (aHR = 1.05; 0.76-1.44), myocardial infarction (aHR = 0.82; 0.63-1.06), stroke (aHR = 0.83; 0.62-1.12), or irritable bowel syndrome (HR = 0.94; 0.61-1.45). Similarly, we found no association of CDI with FMT (vs mrCDI without FMT) and diabetes (aHR = 0.92; 0.27-3.11), hypertension (aHR = 1.41; 0.64-3.15), stroke (aHR = 1.27; 0.69-2.34) or inflammatory bowel syndrome (aHR = 0.80; 0.26-2.46). However, the incidence of myocardial infarction was increased following FMT (aHR = 1.68; 1.01-2.81).<br><br>CONCLUSION: Relative to those with CDI, persons with mrCDI do not appear to be intrinsically at higher risk of cardiometabolic, immune-mediated diseases, or irritable bowel syndrome. However, those who underwent FMT for CDI had a higher incidence of myocardial infarction. Future studies should assess this association to assess reproducibility.}, }
@article {pmid33307092, year = {2021}, author = {Mamic, P and Chaikijurajai, T and Tang, WHW}, title = {Gut microbiome - A potential mediator of pathogenesis in heart failure and its comorbidities: State-of-the-art review.}, journal = {Journal of molecular and cellular cardiology}, volume = {152}, number = {}, pages = {105-117}, pmid = {33307092}, issn = {1095-8584}, support = {F32 HL143916/HL/NHLBI NIH HHS/United States ; R01 DK106000/DK/NIDDK NIH HHS/United States ; R01 HL126827/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Comorbidity ; *Gastrointestinal Microbiome ; Heart Failure/epidemiology/microbiology/*pathology ; Humans ; }, abstract = {Gut microbiome (GMB) has been increasingly recognized as a contributor to development and progression of heart failure (HF), immune-mediated subtypes of cardiomyopathy (myocarditis and anthracycline-induced cardiotoxicity), response to certain cardiovascular drugs, and HF-related comorbidities, such as chronic kidney disease, cardiorenal syndrome, insulin resistance, malnutrition, and cardiac cachexia. Gut microbiome is also responsible for the "gut hypothesis" of HF, which explains the adverse effects of gut barrier dysfunction and translocation of GMB on the progression of HF. Furthermore, accumulating evidence has suggested that gut microbial metabolites, including short chain fatty acids, trimethylamine N-oxide (TMAO), amino acid metabolites, and bile acids, are mechanistically linked to pathogenesis of HF, and could, therefore, serve as potential therapeutic targets for HF. Even though there are a variety of proposed therapeutic approaches, such as dietary modifications, prebiotics, probiotics, TMAO synthesis inhibitors, and fecal microbial transplant, targeting GMB in HF is still in its infancy and, indeed, requires further preclinical and clinical evidence. In this review, we aim to highlight the role gut microbiome plays in HF pathophysiology and its potential as a novel therapeutic target in HF.}, }
@article {pmid33304339, year = {2020}, author = {Napolitano, M and Covasa, M}, title = {Microbiota Transplant in the Treatment of Obesity and Diabetes: Current and Future Perspectives.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {590370}, pmid = {33304339}, issn = {1664-302X}, abstract = {A wealth of evidence has revealed the critical role of the gut microbiota in health and disease. Many chronic diseases have been associated with gut microbiota imbalance in its composition, diversity and functional capacity. Several types of interventions have been shown to correct microbiota imbalance and restore the beneficial metabolic outcomes of a normal microbiota. Among them, fecal microbiota transplantation (FMT) is an emergent, promising technology employed to improve clinical outcomes of various pathological conditions through modifications in the gut microbiota composition. FMT has been used successfully as a treatment option in recurrent Clostridium difficile infection, a condition characterized by severe gut microbiota dysbiosis. However, the potential usage of FMT in other microbiota-associated conditions different from C. difficile such as metabolic syndrome or obesity that are also marked by gut dysbiosis is still under investigation. Furthermore, the contribution of the gut microbiota as a cause or consequence in metabolic disease is still largely debated. This review provides critical information on the methodological approaches of FMT and its technological innovation in clinical applications. This review sheds light on the current findings and gaps in our understanding of how FMT can be used as a future biotherapeutic to restore microbial homeostasis in amelioration of obesity and diabetes.}, }
@article {pmid33303685, year = {2021}, author = {Baruch, EN and Youngster, I and Ben-Betzalel, G and Ortenberg, R and Lahat, A and Katz, L and Adler, K and Dick-Necula, D and Raskin, S and Bloch, N and Rotin, D and Anafi, L and Avivi, C and Melnichenko, J and Steinberg-Silman, Y and Mamtani, R and Harati, H and Asher, N and Shapira-Frommer, R and Brosh-Nissimov, T and Eshet, Y and Ben-Simon, S and Ziv, O and Khan, MAW and Amit, M and Ajami, NJ and Barshack, I and Schachter, J and Wargo, JA and Koren, O and Markel, G and Boursi, B}, title = {Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6529}, pages = {602-609}, doi = {10.1126/science.abb5920}, pmid = {33303685}, issn = {1095-9203}, mesh = {Adult ; Antineoplastic Agents, Immunological/*therapeutic use ; CD8-Positive T-Lymphocytes/immunology ; Fecal Microbiota Transplantation/*adverse effects ; Female ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy ; Intestinal Mucosa/immunology/microbiology ; Lymphocytes, Tumor-Infiltrating/immunology ; Male ; Melanoma/*therapy ; Middle Aged ; Nivolumab/*therapeutic use ; Programmed Cell Death 1 Receptor/*antagonists &amp; inhibitors/immunology ; Skin Neoplasms/*therapy ; Transcriptome ; Tumor Microenvironment/genetics/immunology ; }, abstract = {The gut microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death-1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment.}, }
@article {pmid33303563, year = {2021}, author = {Haifer, C and Saikal, A and Paramsothy, R and Kaakoush, NO and Leong, RW and Borody, TJ and Kamm, MA and Paramsothy, S}, title = {Response to faecal microbiota transplantation in ulcerative colitis is not sustained long term following induction therapy.}, journal = {Gut}, volume = {70}, number = {11}, pages = {2210-2211}, doi = {10.1136/gutjnl-2020-323581}, pmid = {33303563}, issn = {1468-3288}, mesh = {*Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Induction Chemotherapy ; }, }
@article {pmid33301807, year = {2021}, author = {Jing, Y and Bai, F and Yu, Y}, title = {Spinal cord injury and gut microbiota: A review.}, journal = {Life sciences}, volume = {266}, number = {}, pages = {118865}, doi = {10.1016/j.lfs.2020.118865}, pmid = {33301807}, issn = {1879-0631}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; *Neuroprotection ; Spinal Cord Injuries/microbiology/*prevention &amp; control ; }, abstract = {After spinal cord injury (SCI), intestinal dysfunction has a serious impact on physical and mental health, quality of life, and social participation. Recent data from rodent and human studies indicated that SCI causes gut dysbiosis. Remodeling gut microbiota could be beneficial for the recovery of intestinal function and motor function after SCI. However, few studies have explored SCI with focus on the gut microbiota and "microbiota-gut-brain" axis. In this review, the complications following SCI, including intestinal dysfunction, anxiety and depression, metabolic disorders, and neuropathic pain, are directly or indirectly related to gut dysbiosis, which may be mediated by "gut-brain" interactions. Furthermore, we discuss the research strategies that can be beneficial in this regard, including germ-free animals, fecal microbiota transplantation, probiotics, phages, and brain imaging techniques. The current microbial research has shifted from descriptive to mechanismal perspective, and future research using new technologies may further demonstrate the pathophysiological mechanism of association of SCI with gut microbiota, elucidate the mode of interaction of gut microbiota and hosts, and help develop personalized microbiota-targeted therapies and drugs based on microbiota or corresponding metabolites.}, }
@article {pmid33301497, year = {2020}, author = {Hyde, MK and Masser, BM}, title = {Determinants of community members' willingness to donate stool for faecal microbiota transplantation.}, journal = {PloS one}, volume = {15}, number = {12}, pages = {e0243751}, pmid = {33301497}, issn = {1932-6203}, mesh = {Adult ; Australia ; Cross-Sectional Studies ; *Donor Selection/methods ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Motivation ; Surveys and Questionnaires ; *Tissue Donors ; Young Adult ; }, abstract = {Universal stool banks rely on, but face difficulties recruiting, community volunteers to donate stool for faecal microbiota transplantation (FMT) to effectively treat recurrent Clostridioides difficile. This study sought to identify determinants of community members' willingness to donate stool to guide donor recruitment. 397 Australian residents (52% male, 47% 21-30 years, 63% university educated) completed a survey to gauge willingness to donate stool, bowel habits, information needs, attitudes, barriers, and motives for donation. Most reported regular bowel movements (BMs; 90%), morning BMs (63%), BMs ≤5 minutes duration (67%), and some discomfort doing BMs in public restrooms (69%). Less than half were willing to donate stool in-centre (45% willing) or at home (48%). Important information needs identified by >80% were convenience and travel requirements associated with donation. Main barriers were logistics, capabilities to donate, disgust (e.g., donation process), and discomfort (e.g., privacy). The main motivator was altruism, with compensation secondary. Linear regression models identified less discomfort doing BMs in public restrooms (β = -0.15), understanding benefits to patients (β = 0.15), placing less importance on understanding the donation process (β = -0.13), and positive attitudes (β = 0.56) as determinants of willingness to donate in-centre. Understanding benefits to self (β = 0.11) and patients (β = 0.24), placing less importance on understanding the donation purpose (β = -0.19), and positive attitudes (β = 0.50) determined willingness to donate at home. Stool banks should consider donor's bowel habits, comfort donating in-centre, and information needs early in recruitment; and implement flexible logistics for potential donors who face time constraints and limited access to stool banks.}, }
@article {pmid33295040, year = {2021}, author = {Taghinezhad-S, S and Mohseni, AH and Fu, X}, title = {Intervention on gut microbiota may change the strategy for management of colorectal cancer.}, journal = {Journal of gastroenterology and hepatology}, volume = {36}, number = {6}, pages = {1508-1517}, doi = {10.1111/jgh.15369}, pmid = {33295040}, issn = {1440-1746}, support = {81972315//National Science Foundation of China/ ; }, mesh = {Colorectal Neoplasms/etiology/*microbiology/*therapy ; Diet ; Digestive System Surgical Procedures/methods ; Drug Therapy/methods ; Dysbiosis ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy/methods ; Male ; Prebiotics ; Probiotics/therapeutic use ; Radiotherapy ; }, abstract = {Dysbiosis in the gut microbiota composition due to environmental or genetic variations can disrupt the immune system and may promote several diseases such as colorectal cancer (CRC). Gut microbiota can alter the toxicity and efficiency of an extensive range of CRC treatment methods, especially surgery, chemotherapy, radiotherapy, and immunotherapy. The recent scientific evidence suggested that gut microbiota modulation exhibits an essential positive influence on inhibition and treatment of CRC. The literature survey revealed that modulating the gut microbiota composition by probiotics, prebiotics, and diets protects CRC patients from treatment-associated adverse effects. This review summarizes the recent advancements in the association between interventions on gut microbiota and CRC to provide innovative strategies for enhancing the safety and efficiency of CRC therapy.}, }
@article {pmid33293406, year = {2020}, author = {Liu, Z and Coales, I and Penney, N and McDonald, JAK and Phetcharaburanin, J and Seyfried, F and Li, JV}, title = {A Subset of Roux-en-Y Gastric Bypass Bacterial Consortium Colonizes the Gut of Nonsurgical Rats without Inducing Host-Microbe Metabolic Changes.}, journal = {mSystems}, volume = {5}, number = {6}, pages = {}, pmid = {33293406}, issn = {2379-5077}, support = {MR/P002536/1/MRC_/Medical Research Council/United Kingdom ; MR/P028225/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Roux-en-Y gastric bypass (RYGB) is an effective weight loss surgery, resulting in a characteristic increase of fecal Gammaproteobacteria The contribution of this compositional change to metabolic benefits of RYGB is currently debatable. Therefore, this study employed 16S rRNA gene sequencing and metabolic profiling to monitor the dynamic colonization of the RYGB microbial consortium and their metabolic impact on the host. Eleven Wistar rats received vancomycin and enrofloxacin, followed by fecal microbiota transplantation (FMT) of cecal slurry obtained from either RYGB- or sham-operated rats. Urine and feces from the microbiota recipients (RYGB microbiota recipients [RYGBr], n = 6; sham microbiota recipients [SHAMr], n = 5) were collected pre- and post-antibiotics and 1, 3, 6, 9, and 16 days post-FMT. No significant differences in body weight and food intake were observed between RYGBr and SHAMr. While neither group reached the community richness of that of their donors, by day 6, both groups reached the richness and diversity of that prior to antibiotic treatment. However, the typical signature of RYGB microbiome-increased Enterobacteriaceae-was not replicated in these recipients after two consecutive FMT, suggesting that the environmental changes induced by the anatomical rearrangements of RYGB could be key for sustaining such a consortium. The transplanted bacteria did not induce the same metabolic signature of urine and feces as those previously reported in RYGB-operated rats. Future work is required to explore environmental factors that shape the RYGB microbiota in order to further investigate the metabolic functions of the RYGB microbiota, thereby teasing out the mechanisms of the RYGB surgery.IMPORTANCE Roux-en-Y gastric bypass (RYGB) surgery results in a long-term gut bacterial shift toward Gammaproteobacteria in both patients and rodents. The contribution of this compositional shift, or the RYGB bacterial consortium, to the metabolic benefit of the surgery remains debatable. It is unclear how well these bacteria colonize in an anatomically normal gut. This is a fundamental question in both defining the function of the RYGB microbiota and evaluating its potential as a nonsurgical treatment for obesity. We monitored the dynamic colonization of the RYGB bacterial consortium and observed that while approximately one-third of the bacterial taxa from the RYGB donor colonized in the gut of the nonoperated recipients, Gammaproteobacteria were unable to colonize for longer than 3 days. The study highlighted that a successful long-term colonization of Gammaproteobacteria-rich RYGB microbiota in nonsurgical animals requires key environmental factors that may be dictated by the intestinal anatomical modification by the surgery itself.}, }
@article {pmid33292670, year = {2020}, author = {Yu, J and Sun, H and Cao, W and Han, L and Song, Y and Wan, D and Jiang, Z}, title = {Applications of gut microbiota in patients with hematopoietic stem-cell transplantation.}, journal = {Experimental hematology &amp; oncology}, volume = {9}, number = {1}, pages = {35}, pmid = {33292670}, issn = {2162-3619}, support = {20A320062//Foundation of Henan Educational Committee/ ; LHGJ20190039//Science and Technology Department of Henan Province/ ; }, abstract = {Studies of the gut microbiota (GM) have demonstrated the close link between human wellness and intestinal commensal bacteria, which mediate development of the host immune system. The dysbiosis, a disruption of the microbiome natural balance, can cause serious health problems. Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cause significant changes in GM due to their underlying malignancies and exposure to extensive chemotherapy and systemic antibiotics, which may lead to different disorders. There are complex and multi-directional interactions among intestinal inflammation, GM and immune reactivity after HSCT. There is considerable effect of the human intestinal microbiome on clinical course following HSCT. Some bacteria in the intestinal ecosystem may be potential biomarkers or therapeutic targets for preventing relapse and improving survival rate after HSCT. Microbiota can be used as predictor of mortality in allo-HSCT. Two different strategies with targeted modulation of GM, preemptive and therapeutic, have been used for preventing or treating GM dysbiosis in patients with HSCT. Preemptive strategies include enteral nutrition (EN), prebiotic, probiotic, fecal microbiota transplantation (FMT) and antibiotic strategies, while therapeutic strategies include FMT, probiotic and lactoferrine usages. In this review, we summarize the advance of therapies targeting GM in patients with HSCT.}, }
@article {pmid33284460, year = {2021}, author = {Liu, H and Qin, Y and Li, K and Li, M and Yang, J and Tao, H and Tang, Y and Yang, L and Chen, S and Liu, Y and Yang, C and Gao, W and Sun, T}, title = {Potential type 2 diabetes mellitus drug HMPA promotes short-chain fatty acid production by improving carbon catabolite repression effect of gut microbiota.}, journal = {British journal of pharmacology}, volume = {178}, number = {4}, pages = {946-963}, doi = {10.1111/bph.15338}, pmid = {33284460}, issn = {1476-5381}, support = {81703581//National Natural Science Foundation of China/ ; 81972629//National Natural Science Foundation of China/ ; 81871972//National Natural Science Foundation of China/ ; 81572838//National Natural Science Foundation of China/ ; 81872374//National Natural Science Foundation of China/ ; BX20180150//Postdoctoral support scheme for innovative talents/ ; 2018M640228//Project funded by China Postdoctoral Science Foundation/ ; 2018YFA0507203//The National Key Research and Development Program of China/ ; 18PTSYJC00060//Tianjin Science and Technology Committee/ ; tsqn201909193//Taishan Scholars Program of Shandong Province/ ; //Fundamental Research Funds for the Central Universities, Nankai University/ ; SQ2018ZX090201//Chinese National Major Scientific and Technological Special Project for "Significant New Drugs Development"/ ; 2018ZX09736-005//Chinese National Major Scientific and Technological Special Project for "Significant New Drugs Development"/ ; }, mesh = {*Catabolite Repression ; *Diabetes Mellitus, Type 2 ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome ; Hempa ; Humans ; *Pharmaceutical Preparations ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND AND PURPOSE: Gut microbiota plays an important role in type 2 diabetes mellitus (T2DM) progression. From our previous work N-(4-Hydroxyphenethyl)-3-mercapto-2-methylpropanamide (HMPA) is a potential T2DM drug. We evaluated the effect of HMPA on gut microbiota and studied the molecular mechanism underlying HMPA's regulation of gut microbiota.<br><br>EXPERIMENTAL APPROACH: The pseudo germ-free (PGF) T2DM model and faecal microbiota transplantation method were used to study whether gut microbiota mediates the actions of HMPA. The composition of gut microbiota was detected by using 16S rRNA sequence. Short-chain fatty acids (SCFAs) content was detected by gas chromatography. The HMPA probe was synthesised for finding and identifying the target protein of HMPA. The effect of HMPA on the utilisation of carbon sources in Bifidobacterium was evaluated.<br><br>KEY RESULTS: HMPA has a slight effect on the PGF T2DM model. The gut microbiota changed by HMPA can also alleviate the symptoms of T2DM. HMPA can regulate gut microbiota structure, increase SCFAs production and reduce nitrate content in the intestinal tissues. The thickness of the mucus on colon tissues increases after HMPA treatment. The target protein of HMPA in gut microbiota is the nitrogen metabolism global transcriptional regulator (GlnR). HMPA promotes the utilisation of less preferred carbon source in the gut microbiota and increases the fermentation product of SCFAs.<br><br>CONCLUSION AND IMPLICATIONS: HMPA plays a hypoglycaemic role through the gut microbiota. HMPA improves the carbon catabolite repression effect of gut microbiota and increases SCFAs production by targeting GlnR. GlnR may be a target for gut microbiota regulation.}, }
@article {pmid33282868, year = {2020}, author = {Liu, TH and Tao, WC and Liang, QE and Tu, WQ and Xiao, Y and Chen, LG}, title = {Gut Microbiota-Related Evidence Provides New Insights Into the Association Between Activating Transcription Factor 4 and Development of Salt-Induced Hypertension in Mice.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {585995}, pmid = {33282868}, issn = {2296-634X}, abstract = {Activating transcription factor 4 (ATF4), which regulates genes associated with endoplasmic reticulum stress, apoptosis, autophagy, the gut microbiome, and metabolism, has been implicated in many diseases. However, its mechanistic role in hypertension remains unclear. In the present study, we investigated its role in salt-sensitive hypertensive mice. Wild-type (WT) C57BL/6J mice were used to establish Atf4 knockout (KO) and overexpression mice using CRISPR-Cas9 and lentiviral overexpression vectors. Then, fecal microbiota transplantation (FMT) from Atf4 [±] mice and vitamin K2 (VK2) supplementation were separately carried out in high-salt-diet (8% NaCl)-induced mice for 4 weeks. We found that Atf4 KO inhibited and Atf4 overexpression enhanced the increase in blood pressure and endothelial dysfunction induced by high salt intake in mice, while regulating the gut microbiota composition and VK2 expression. It was further verified that ATF4 is involved in the regulation of salt-sensitive hypertension and vascular endothelial function, which is achieved through association with gut microbiota and may be related to VK2 and different bacteria such as Dubosiella. In addition, we found that VK2 supplementation prevents the development of salt-sensitive hypertension and maintains vascular endothelial function; moreover, VK2 supplementation increases the abundance of intestinal Dubosiella and downregulates the relative expression of Atf4 in the thoracic aorta of mice. We conclude that ATF4 plays an important role in regulating gut microbiota and VK2 production, providing new insights into the association between ATF4 and development of salt-induced hypertension in mice, meanwhile contributing to the development for a new preventive strategy of hypertension.}, }
@article {pmid33281758, year = {2020}, author = {Jansen, SA and Nijhuis, W and Leavis, HL and Riezebos-Brilman, A and Lindemans, CA and Schuurman, R}, title = {Broad Virus Detection and Variant Discovery in Fecal Samples of Hematopoietic Transplant Recipients Using Targeted Sequence Capture Metagenomics.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {560179}, pmid = {33281758}, issn = {1664-302X}, abstract = {Pediatric allogeneic hematopoietic stem cell transplantation (HSCT) patients often suffer from gastro-intestinal (GI) disease caused by viruses, Graft-versus-Host Disease (GVHD) or a combination of the two. Currently, the GI eukaryotic virome of HSCT recipients remains relatively understudied, which complicates the understanding of its role in GVHD pathogenicity. As decisions regarding immunosuppressive therapy in the treatment of virus infection or GVHD, respectively, can be completely contradicting, it is crucial to better understand the prevalence and relevance of viruses in the GI tract in the HSCT setting. A real time PCR panel for a set of specific viruses widely used to diagnose the most common causes of GI viral gastroenteritis is possibly insufficient to grasp the full extent of viruses present. Therefore, we applied the targeted sequence capture method ViroCap to residual fecal samples of 11 pediatric allogeneic HSCT recipients with GI symptoms and a suspicion of GVHD, to enrich for nucleic acids of viruses that are known to infect vertebrate hosts. After enrichment, NGS was applied to broadly detect viral sequences. Using ViroCap, we were able to detect viruses such as norovirus and adenovirus (ADV), that had been previously detected using clinical diagnostic PCR on the same sample. In addition, multiple, some of which clinically relevant viruses were detected, including ADV, human rhinovirus (HRV) and BK polyomavirus (BKV). Interestingly, in samples in which specific PCR testing for regular viral GI pathogens did not result in a diagnosis, the ViroCap pipeline led to the detection of viral sequences of human herpesvirus (HHV)-7, BKV, HRV, KI polyomavirus and astrovirus. The latter was an only recently described variant and showed extensive sequence mismatches with the applied real time PCR primers and would therefore not have been detected if tested. Our results indicate that target enrichment of viral nucleic acids through ViroCap leads to sensitive and broad possibly clinically relevant virus detection, including the detection of newer variants in clinical HSCT recipient samples. As such, ViroCap could be a useful detection tool clinically, but also in studying the associations between viral presence and GVHD.}, }
@article {pmid33279615, year = {2021}, author = {Zhang, P and Zhang, X and Huang, Y and Chen, J and Shang, W and Shi, G and Zhang, L and Zhang, C and Chen, R}, title = {Atorvastatin alleviates microglia-mediated neuroinflammation via modulating the microbial composition and the intestinal barrier function in ischemic stroke mice.}, journal = {Free radical biology &amp; medicine}, volume = {162}, number = {}, pages = {104-117}, doi = {10.1016/j.freeradbiomed.2020.11.032}, pmid = {33279615}, issn = {1873-4596}, mesh = {Animals ; Atorvastatin ; *Brain Ischemia/drug therapy ; *Ischemic Stroke ; Mice ; Mice, Inbred C57BL ; Microglia ; *Stroke/drug therapy ; }, abstract = {Our previous work has shown that atorvastatin exerts anti-inflammatory properties in ischemic stroke, and recent studies have revealed that intestinal microbiota plays a vital role in the pathogenesis of stroke. However, it is not clear whether the anti-inflammatory effects of atorvastatin against ischemic stroke is related to gut function and microbiota. We report herein that atorvastatin significantly ameliorated the defects in sensorimotor behaviors and reduced microglia-mediated neuroinflammation by inhibiting proinflammatory polarization of microglia in the peri-infarct cortex of the mice with permanent middle cerebral artery occlusion (pMCAO). Moreover, atorvastatin reversed microbial composition (characterized by increased abundance of Firmicutes and Lactobacillus and decreased Bacteroidetes abundance), increased fecal butyrate level, promoted intestinal barrier function (elevated protein levels of claudin-1, occludin and mucoprotein 2), as well as regulated intestinal immune function (decreased MCP-1, TNF-α and increased IL-10). Atorvastatin also significantly reduced the level of circulating endotoxin (lipopolysaccharide-binding protein), which is a biomarker of leaky gut. Transplantation of fecal microbiota collected from atorvastatin treated mice potently attenuated neuroinflammation in pMCAO mice, and the anti-inflammatory effects of fecal microbiota transplantation were similar to those of oral atorvastatin administration. These results suggested that the atorvastatin-mediated restoration of gut microbiota, improvement of intestinal barrier function and regulation of intestinal immunity were involved in the anti-inflammatory function in stroke mice.}, }
@article {pmid33279588, year = {2021}, author = {Huang, L and Duan, C and Xia, X and Wang, H and Wang, Y and Zhong, Z and Wang, B and Ding, W and Yang, Y}, title = {Commensal microbe-derived propionic acid mediates juvenile social isolation-induced social deficits and anxiety-like behaviors.}, journal = {Brain research bulletin}, volume = {166}, number = {}, pages = {161-171}, doi = {10.1016/j.brainresbull.2020.12.001}, pmid = {33279588}, issn = {1873-2747}, mesh = {Animals ; Anxiety/*metabolism ; Behavior, Animal ; Gastrointestinal Microbiome/*physiology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Prefrontal Cortex/*metabolism ; Propionates/*metabolism ; Receptors, Oxytocin/*metabolism ; *Social Isolation ; }, abstract = {Social experiences during early life are thought to be critical for proper social and emotional development. Conversely, social insults during development causes long-lasting behavioral abnormalities later in life. However, how juvenile social deprivation influences social and emotional behaviors remains poorly understood. Here, we show that juvenile social isolation induces a shift in microbial ecology that negatively impacts social and emotional behaviors in adulthood. These behavioral changes, which occur during this critical period are transferable to antibiotic pre-treated mice by fecal microbiota transplant. In addition, juvenile social isolation decreases the expression of oxytocin receptor (OXTR) in the medial prefrontal cortex (mPFC), and increases the amounts of fecal propionic acid (PA), a short-chain fatty acid derived from gut micobiota. Accordingly, infusion with an OXTR antagonist (OXTR-A, l-368,899) specifically in the mPFC or supplementation of PA both can cause social deficits and anxiety-like behaviors in group housed mice. Collectively, our findings reveal that juvenile social experience regulates prefrontal cortical OXTR expression through gut microbiota-produced PA and that is essential for normal social and emotional behaviors, thus providing a cellular and molecular context to understand the consequences of juvenile social deprivation.}, }
@article {pmid33278650, year = {2021}, author = {Mehta, SR and Yen, EF}, title = {Microbiota-based Therapies Clostridioides difficile infection that is refractory to antibiotic therapy.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {230}, number = {}, pages = {197-207}, doi = {10.1016/j.trsl.2020.11.013}, pmid = {33278650}, issn = {1878-1810}, mesh = {Anti-Bacterial Agents/*pharmacology ; Clostridioides difficile/*drug effects ; Clostridium Infections/*drug therapy/*microbiology ; Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Clostridioides difficile infection (CDI) has had a devastating impact worldwide with significant rates of mortality, especially among the elderly. Despite effective antibiotics, the incidence of recurrent CDI (rCDI) is increasing and more difficult to treat with antibiotics alone. Fecal Microbiota Transplantation (FMT) has emerged as a consistently effective treatment for rCDI. Mechanisms for FMT are not entirely understood, but remain an area of active investigation. There have been recent safety reports with the use of FMT regarding transmission of pathogens in a few patients that have led to serious illness. With appropriate screening, FMT can be safely administered and continue to have a significant impact on eradication of rCDI and improve the lives of patients suffering from this disease. In this review, we summarize current treatments for CDI with a focus on microbiota-based therapies used for antibiotic refractory disease.}, }
@article {pmid33277629, year = {2021}, author = {Maghini, DG and Moss, EL and Vance, SE and Bhatt, AS}, title = {Improved high-molecular-weight DNA extraction, nanopore sequencing and metagenomic assembly from the human gut microbiome.}, journal = {Nature protocols}, volume = {16}, number = {1}, pages = {458-471}, pmid = {33277629}, issn = {1750-2799}, support = {P30 CA124435/CA/NCI NIH HHS/United States ; P50 AG047366/AG/NIA NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; }, mesh = {DNA/genetics/isolation &amp; purification ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Metagenome ; *Microbiota ; Nanopore Sequencing/*methods ; Sequence Analysis, DNA/*methods ; }, abstract = {Short-read metagenomic sequencing and de novo genome assembly of the human gut microbiome can yield draft bacterial genomes without isolation and culture. However, bacterial genomes assembled from short-read sequencing are often fragmented. Furthermore, these metagenome-assembled genomes often exclude repeated genomic elements, such as mobile genetic elements, compromising our understanding of the contribution of these elements to important bacterial phenotypes. Although long-read sequencing has been applied successfully to the assembly of contiguous bacterial isolate genomes, extraction of DNA of sufficient molecular weight, purity and quantity for metagenomic sequencing from stool samples can be challenging. Here, we present a protocol for the extraction of microgram quantities of high-molecular-weight DNA from human stool samples that are suitable for downstream long-read sequencing applications. We also present Lathe (www.github.com/bhattlab/lathe), a computational workflow for long-read basecalling, assembly, consensus refinement with long reads or Illumina short reads and genome circularization. Altogether, this protocol can yield high-quality contiguous or circular bacterial genomes from a complex human gut sample in approximately 10 d, with 2 d of hands-on bench and computational effort.}, }
@article {pmid33277504, year = {2020}, author = {Tian, L and Wang, XW and Wu, AK and Fan, Y and Friedman, J and Dahlin, A and Waldor, MK and Weinstock, GM and Weiss, ST and Liu, YY}, title = {Deciphering functional redundancy in the human microbiome.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6217}, pmid = {33277504}, issn = {2041-1723}, support = {K01 HL130629/HL/NHLBI NIH HHS/United States ; R01 AI042347/AI/NIAID NIH HHS/United States ; U19 AI095219/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/classification/genetics ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Gene Regulatory Networks ; Gene Transfer, Horizontal ; Humans ; Metagenome/*genetics ; Metagenomics/*methods ; Microbiota/*genetics ; Models, Genetic ; }, abstract = {Although the taxonomic composition of the human microbiome varies tremendously across individuals, its gene composition or functional capacity is highly conserved - implying an ecological property known as functional redundancy. Such functional redundancy has been hypothesized to underlie the stability and resilience of the human microbiome, but this hypothesis has never been quantitatively tested. The origin of functional redundancy is still elusive. Here, we investigate the basis for functional redundancy in the human microbiome by analyzing its genomic content network - a bipartite graph that links microbes to the genes in their genomes. We find that this network exhibits several topological features that favor high functional redundancy. Furthermore, we develop a simple genome evolution model to generate genomic content network, finding that moderate selection pressure and high horizontal gene transfer rate are necessary to generate genomic content networks with key topological features that favor high functional redundancy. Finally, we analyze data from two published studies of fecal microbiota transplantation (FMT), finding that high functional redundancy of the recipient's pre-FMT microbiota raises barriers to donor microbiota engraftment. This work elucidates the potential ecological and evolutionary processes that create and maintain functional redundancy in the human microbiome and contribute to its resilience.}, }
@article {pmid33276482, year = {2020}, author = {Tanase, DM and Gosav, EM and Neculae, E and Costea, CF and Ciocoiu, M and Hurjui, LL and Tarniceriu, CC and Maranduca, MA and Lacatusu, CM and Floria, M and Serban, IL}, title = {Role of Gut Microbiota on Onset and Progression of Microvascular Complications of Type 2 Diabetes (T2DM).}, journal = {Nutrients}, volume = {12}, number = {12}, pages = {}, pmid = {33276482}, issn = {2072-6643}, mesh = {Animals ; Diabetes Mellitus, Type 2/*metabolism/therapy ; Diabetic Retinopathy ; *Disease Progression ; Dysbiosis ; Fatty Acids, Volatile ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Insulin Resistance ; Metabolic Syndrome/complications ; }, abstract = {Type 2 diabetes mellitus (T2DM) remains one of the most problematic and economic consumer disorders worldwide, with growing prevalence and incidence. Over the last years, substantial research has highlighted the intricate relationship among gut microbiota, dysbiosis and metabolic syndromes development. Changes in the gut microbiome composition lead to an imbalanced gastrointestinal habitat which promotes abnormal production of metabolites, inflammatory status, glucose metabolism alteration and even insulin resistance (IR). Short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), lipopolysaccharide, aromatic amino acids and their affiliated metabolites, contribute to T2DM via different metabolic and immunologic pathways. In this narrative review, we discuss the immunopathogenic mechanism behind gut dysbiosis, T2DM development and the major known diabetic microvascular complications (retinopathy, neuropathy and nephropathy), the beneficial use of pre- and pro-biotics and fecal microbiota transplantation in T2DM management and new findings and future perspectives in this field.}, }
@article {pmid33275940, year = {2021}, author = {Vendrik, KEW and Terveer, EM and Kuijper, EJ and Nooij, S and Boeije-Koppenol, E and Sanders, IMJG and van Lingen, E and Verspaget, HW and Berssenbrugge, EKL and Keller, JJ and van Prehn, J and , }, title = {Periodic screening of donor faeces with a quarantine period to prevent transmission of multidrug-resistant organisms during faecal microbiota transplantation: a retrospective cohort study.}, journal = {The Lancet. Infectious diseases}, volume = {21}, number = {5}, pages = {711-721}, doi = {10.1016/S1473-3099(20)30473-4}, pmid = {33275940}, issn = {1474-4457}, mesh = {Adult ; *Drug Resistance, Multiple, Bacterial/drug effects/genetics ; Escherichia coli/drug effects ; Escherichia coli Infections/*prevention &amp; control/*transmission ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Humans ; Male ; Microbiota ; Middle Aged ; Multilocus Sequence Typing ; Netherlands ; *Quarantine ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: On June 13, 2019, the US Food and Drug Administration issued a warning after transfer of faeces containing an extended-spectrum β-lactamase (ESBL)-producing Escherichia coli by faecal microbiota transplantation led to bacteraemia in two immunocompromised patients. Consequently, we evaluated the effectiveness of the faeces donor-screening protocol of the Netherlands Donor Faeces Bank, which consists of screening of donors for multidrug-resistant organisms every 3 months, combined with additional screening on indication (eg, after travelling abroad) and application of a quarantine period for all faecal suspensions delivered within those 3 months.<br><br>METHODS: We did a retrospective cohort study of data collected between Jan 1, 2015, and Oct 14, 2019, on the multidrug-resistant organism testing results of donor faeces. Additionally, we tested previously quarantined faecal suspensions approved for faecal microbiota transplantation between Dec 12, 2016, and May 1, 2019, for the presence of multidrug-resistant organisms using both aselective and selective broth enrichment media. Whole-genome sequencing with core-genome multilocus sequence typing (cgMLST) was done on all multidrug-resistant isolates.<br><br>FINDINGS: Among initial screenings, six (9%) of 66 tested individuals were positive for multidrug-resistant organisms and 11 (17%) of 66 tested individuals were positive for multidrug-resistant organisms at any timepoint. Multidrug-resistant organisms were detected in four (25%) of 16 active donors, who had a median donation duration of 268 days (IQR 92 to 366). Among all screening results, 14 (74%) of 19 detected multidrug-resistant organisms were ESBL-producing E coli. 170 (49%) of 344 approved faecal suspensions had corresponding research faeces aliquots available and were tested (from 11 active donors with a median of eight [IQR five to 26] suspensions per donor). No multidrug-resistant organisms were detected in the 170 approved faecal suspensions (one-sided 95% CI 0 to 1&#xb7;7). cgMLST revealed that all multidrug-resistant organisms were genetically different.<br><br>INTERPRETATION: Healthy faeces donors can become colonised with multidrug-resistant organisms during donation activities. Our screening protocol did not result in approval of multidrug-resistant organism-positive faecal suspensions for microbiota transplantation.<br><br>FUNDING: None.}, }
@article {pmid33275939, year = {2021}, author = {Hohmann, EL}, title = {Faecal microbiota transplantation: more screening for old and new pathogens.}, journal = {The Lancet. Infectious diseases}, volume = {21}, number = {5}, pages = {587-589}, doi = {10.1016/S1473-3099(20)30850-1}, pmid = {33275939}, issn = {1474-4457}, mesh = {Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; Feces ; Humans ; *Quarantine ; Retrospective Studies ; }, }
@article {pmid33275263, year = {2020}, author = {Monne, M and Asproni, R and Fancello, T and Piras, G and Sulis, V and Floris, AR and Sanna, F and Toja, A and Paffi, P and Carai, A and Mameli, G and Fiamma, M}, title = {SARS-CoV-2 systemic infection in a kidney transplant recipient: sequence analysis in clinical specimens.}, journal = {European review for medical and pharmacological sciences}, volume = {24}, number = {22}, pages = {11914-11918}, doi = {10.26355/eurrev_202011_23850}, pmid = {33275263}, issn = {2284-0729}, mesh = {COVID-19/*virology ; Feces/chemistry/*virology ; Female ; Graft Rejection/prevention &amp; control ; High-Throughput Nucleotide Sequencing ; Humans ; Immunosuppressive Agents/therapeutic use ; *Kidney Transplantation ; Middle Aged ; Mutation, Missense/genetics ; Nasopharynx/chemistry/*virology ; Phylogeny ; Polyproteins/genetics ; RNA, Viral/blood/*genetics ; SARS-CoV-2/genetics ; Sequence Analysis, RNA ; Viral Proteins/*genetics ; }, abstract = {OBJECTIVE: Herein we report clinical and virological data in a patient with COVID-19 infection and a prior history of kidney transplantation who had a good clinical recovery despite systemic infection.<br><br>PATIENTS AND METHODS: Reverse transcriptase quantitative PCR analysis for the RdRp, N and E target genes detected viral RNA in different types of biological specimens. Whole viral genome sequences were obtained and analyzed from respiratory tract, feces and blood.<br><br>RESULTS: Viral sequences showed high (~99.9%) homology with the Wuhan seafood market pneumonia virus. Phylogenetic analysis assigned of the SARS-CoV-2 strains to clade G. A rare variant in the orf1ab gene was present in both sequences, while a missense variant was detected only in viral RNA from stool.<br><br>CONCLUSIONS: The evolution of the COVID-19 systemic infection in the patient presented here was favorable to the hypothesis that immunosuppressive therapy in organ transplant recipients might be involved in viral dissemination. A missense mutation was present in only one specimen from the same patient implying the occurrence of a mutational event in viral RNA, which is suggestive for the presence of an active virus, even though viral isolation is necessary to demonstrate infectivity.}, }
@article {pmid33274207, year = {2020}, author = {Zhan, K and Zheng, H and Li, J and Wu, H and Qin, S and Luo, L and Huang, S}, title = {Gut Microbiota-Bile Acid Crosstalk in Diarrhea-Irritable Bowel Syndrome.}, journal = {BioMed research international}, volume = {2020}, number = {}, pages = {3828249}, pmid = {33274207}, issn = {2314-6141}, mesh = {Bile Acids and Salts/*metabolism ; Diarrhea/*microbiology ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*microbiology/therapy ; Signal Transduction ; }, abstract = {The occurrence of diarrhea-predominant irritable bowel syndrome (IBS-D) is the result of multiple factors, and its pathogenesis has not yet been clarified. Emerging evidence indicates abnormal changes in gut microbiota and bile acid (BA) metabolism have a close relationship with IBS-D. Gut microbiota is involved in the secondary BA production via deconjugation, 7α-dehydroxylation, oxidation, epimerization, desulfation, and esterification reactions respectively. Changes in the composition and quantity of gut microbiota have an important impact on the metabolism of BAs, which can lead to the occurrence of gastrointestinal diseases. BAs, synthesized in the hepatocytes, play an important role in maintaining the homeostasis of gut microbiota and the balance of glucose and lipid metabolism. In consideration of the complex biological functional connections among gut microbiota, BAs, and IBS-D, it is urgent to review the latest research progress in this field. In this review, we summarized the alterations of gut microbiota in IBS-D and discussed the mechanistic connections between gut microbiota and BA metabolism in IBS-D, which may be involved in activating two important bile acid receptors, G-protein coupled bile acid receptor 1 (TGR5) and farnesoid X receptor (FXR). We also highlight the strategies of prevention and treatment of IBS-D via regulating gut microbiota-bile acid axis, including probiotics, fecal microbiota transplantation (FMT), cholestyramine, and the cutting-edge technology about bacteria genetic engineering.}, }
@article {pmid33273738, year = {2020}, author = {Ratner, M}, title = {Microbial cocktails raise bar for C. diff. treatments.}, journal = {Nature biotechnology}, volume = {38}, number = {12}, pages = {1366-1367}, doi = {10.1038/s41587-020-00765-8}, pmid = {33273738}, issn = {1546-1696}, mesh = {Clinical Trials, Phase III as Topic ; Clostridioides difficile/*physiology ; Clostridium Infections/*microbiology/therapy ; Drug Approval ; Fecal Microbiota Transplantation ; Humans ; Spores, Bacterial/physiology ; }, }
@article {pmid33273413, year = {2021}, author = {Sabus, A and Merrow, M and Heiden, A and Boster, J and Koo, J and Franklin, ARK}, title = {Fecal Microbiota Transplantation for Treatment of Severe Clostridioides difficile Colitis in a Pediatric Patient With Non-Hodgkin Lymphoma.}, journal = {Journal of pediatric hematology/oncology}, volume = {43}, number = {6}, pages = {e897-e899}, doi = {10.1097/MPH.0000000000002023}, pmid = {33273413}, issn = {1536-3678}, mesh = {Adolescent ; Clostridioides difficile/*physiology ; Clostridium Infections/*complications/microbiology/therapy ; Colitis/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Male ; }, abstract = {BACKGROUND: Patients with malignant diseases are at high risk for refractory Clostridioides difficile infections (CDI). Fecal microbiota transplantation (FMT) restores the gastrointestinal microbiome and may be an effective treatment for patients who fail pharmacotherapy. However, FMT is not commonly used in the oncology population because of risk for donor-derived infection.<br><br>OBSERVATIONS: The authors report successful use of FMT in a pediatric patient with refractory CDI actively receiving chemotherapy. The patient's symptoms improved 1 day following FMT. He did not experience infectious complications or other adverse effects.<br><br>CONCLUSIONS: FMT may be a feasible option for treatment of refractory CDI in pediatric oncology patients.}, }
@article {pmid33271427, year = {2020}, author = {Rosel-Pech, C and Chávez-Torres, M and Bekker-Méndez, VC and Pinto-Cardoso, S}, title = {Therapeutic avenues for restoring the gut microbiome in HIV infection.}, journal = {Current opinion in pharmacology}, volume = {54}, number = {}, pages = {188-201}, doi = {10.1016/j.coph.2020.09.010}, pmid = {33271427}, issn = {1471-4973}, mesh = {Animals ; Dysbiosis/immunology/microbiology ; *Gastrointestinal Microbiome ; HIV Infections/immunology/*microbiology ; Humans ; Immunity, Mucosal ; Intestinal Mucosa/immunology/microbiology ; }, abstract = {The interplay between the gut microbiota, the intestinal barrier and the mucosal immune system is profoundly altered in Human Immunodeficiency Virus (HIV) infection. An HIV-associated microbial dysbiotic signature has been difficult to define due to the strong impact of confounders that are intimately linked with HIV infection, namely HIV risk behaviors. When controlling for sexual preference and gender, HIV-associated microbial dysbiotic signatures are characterized by an increase in deleterious taxa and a decrease in beneficial bacteria and their respective metabolic end-products. First attempts to restore the gut microbiota of HIV subjects on Antiretroviral Therapy using Fecal Microbiota Transplantation proved to be safe and reported mild transient engraftment of donor microbiota and no effect on markers of HIV disease progression. This review focuses on the current evidence supporting a role for microbial dysbiosis in HIV pathogenesis, and reviews current microbiome-based therapeutics for restoring the gut microbiota in HIV infection.}, }
@article {pmid33264299, year = {2020}, author = {Rodriguez-Castaño, GP and Rey, FE and Caro-Quintero, A and Acosta-González, A}, title = {Gut-derived Flavonifractor species variants are differentially enriched during in vitro incubation with quercetin.}, journal = {PloS one}, volume = {15}, number = {12}, pages = {e0227724}, pmid = {33264299}, issn = {1932-6203}, mesh = {Animal Feed ; Animals ; Carbon/metabolism ; Clostridiales/*drug effects/genetics/isolation &amp; purification/metabolism ; Culture Media/pharmacology ; DNA, Bacterial/genetics/isolation &amp; purification ; Dietary Fiber/administration &amp; dosage ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Germ-Free Life ; Humans ; Longitudinal Studies ; Metabolic Networks and Pathways/genetics ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Annotation ; Phylogeny ; Quercetin/*pharmacology ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Ribotyping ; Sequence Analysis, DNA ; Sodium Acetate/pharmacology ; Species Specificity ; }, abstract = {Flavonoids are a common component of the human diet with widely reported health-promoting properties. The gut microbiota transforms these compounds affecting the overall metabolic outcome of flavonoid consumption. Flavonoid-degrading bacteria are often studied in pure and mixed cultures but the multiple interactions between quercetin-degraders and the rest of the community have been overlooked. In this study, a comparative metataxonomic analysis of fecal communities supplemented with the flavonoid quercetin led us to identify a potential competitive exclusion interaction between two sequence variants related to the flavonoid-degrading species, Flavonifractor plautii, that belong to the same genus but different species. During incubation of fecal slurries with quercetin, the relative abundance of these two variants was inversely correlated; one variant, ASV_65f4, increased in relative abundance in half of the libraries and the other variant, ASV_a45d, in the other half. This pattern was also observed with 6 additional fecal samples that were transplanted into germ-free mice fed two different diets. Mouse's diet did not change the pattern of dominance of either variant, and initial relative abundances did not predict which one ended up dominating. Potential distinct metabolic capabilities of these two Flavonifractor-related species were evidenced, as only one variant, ASV_65f4, became consistently enriched in complex communities supplemented with acetate but without quercetin. Genomic comparison analysis of the close relatives of each variant revealed that ASV_65f4 may be an efficient utilizer of ethanolamine which is formed from the phospholipid phosphatidylethanolamine that is abundant in the gut and feces. Other discordant features between ASV_65f4- and ASV_a45d-related groups may be the presence of flagellar and galactose-utilization genes, respectively. Overall, we showed that the Flavonifractor genus harbors variants that present a pattern of negative co-occurrence and that may have different metabolic and morphological traits, whether these differences affect the dynamic of quercetin degradation warrants further investigation.}, }
@article {pmid33263886, year = {2020}, author = {Federici, S and Suez, J and Elinav, E}, title = {Our Microbiome: On the Challenges, Promises, and Hype.}, journal = {Results and problems in cell differentiation}, volume = {69}, number = {}, pages = {539-557}, pmid = {33263886}, issn = {0080-1844}, mesh = {Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Prebiotics ; Probiotics ; }, abstract = {The microbiome field is increasingly raising interest among scientists, clinicians, biopharmaceutical entities, and the general public. Technological advances from the past two decades have enabled the rapid expansion of our ability to characterize the human microbiome in depth, highlighting its previously underappreciated role in contributing to multifactorial diseases including those with unknown etiology. Consequently, there is growing evidence that the microbiome could be utilized in medical diagnosis and patient stratification. Moreover, multiple gut microbes and their metabolic products may be bioactive, thereby serving as future potential microbiome-targeting or -associated therapeutics. Such therapies could include new generation probiotics, prebiotics, fecal microbiota transplantations, postbiotics, and dietary modulators. However, microbiome research has also been associated with significant limitations, technical and conceptual challenges, and, at times, "over-hyped" expectations that microbiome research will produce quick solutions to chronic and mechanistically complex human disorders. Herein, we summarize these challenges and also discuss some of the realistic promises associated with microbiome research and its applicability into clinical application.}, }
@article {pmid33260902, year = {2020}, author = {Grammatikopoulou, MG and Goulis, DG and Gkiouras, K and Nigdelis, MP and Papageorgiou, ST and Papamitsou, T and Forbes, A and Bogdanos, DP}, title = {Low FODMAP Diet for Functional Gastrointestinal Symptoms in Quiescent Inflammatory Bowel Disease: A Systematic Review of Randomized Controlled Trials.}, journal = {Nutrients}, volume = {12}, number = {12}, pages = {}, pmid = {33260902}, issn = {2072-6643}, support = {97509//MSc in Health and Environmental Factors, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece/ ; }, mesh = {Diet ; Dietary Carbohydrates/*administration &amp; dosage ; Humans ; Inflammatory Bowel Diseases/*diet therapy ; Oligosaccharides/*administration &amp; dosage ; Polymers ; }, abstract = {A low FODMAP diet (LFD) has been hypothesized to relieve symptoms of functional gastrointestinal disorders (FGD) in patients with inflammatory bowel disease (IBD). The aim of the study was to systematically review the literature for randomized controlled trials (RCTs) assessing the effectiveness of the LFD in patients with IBD and FGD. Four databases were searched, but a meta-analysis was not performed due to methodological and outcomes heterogeneity. Four RCTs fulfilled the criteria, with three having some concerns in their risk of bias assessment. All interventions compared the LFDs against a "typical" or sham diet, spanning in duration from 21 days to 6 weeks. Quality of life was improved in two RCTs, while revealing inconsistent findings in the third trial, based on different assessment tools. The fecal assays revealed non-significant findings for most variables (fecal weight, pH, water content, gene count, and gut transit time) and inconsistent findings concerning stool frequency and short-chain fatty acids concentration. Levels of fecal calprotectin, CRP, or T-cell phenotype did not differ between intervention and comparator arms. Two RCTs reported a reduction in abdominal pain, while results concerning pain duration and bloating were inconsistent. In one trial, energy intake was considerably reduced among LFD participants. Regarding gut microbiota, no differences were noted. A considerable degree of methodological and outcome heterogeneity was observed, paired with results inconsistency. The available data are not sufficient to justify the claim that an LFD induces relief of FGD symptoms, although it may pave the way to a placebo response.}, }
@article {pmid33259159, year = {2020}, author = {Mamoon, L and Olesen, SW}, title = {Fecal Microbiota Transplants Annually and Their Positive Clinical Impact.}, journal = {Clinical and translational gastroenterology}, volume = {11}, number = {11}, pages = {e00247}, pmid = {33259159}, issn = {2155-384X}, mesh = {Clostridium Infections/diagnosis/epidemiology/*therapy ; Computer Simulation ; Fecal Microbiota Transplantation/*statistics &amp; numerical data ; Health Services Accessibility/*organization &amp; administration/statistics &amp; numerical data ; Humans ; Models, Statistical ; Professional Practice Gaps/*statistics &amp; numerical data ; Recurrence ; Secondary Prevention/methods/*organization &amp; administration/statistics &amp; numerical data ; Treatment Outcome ; United States/epidemiology ; }, abstract = {INTRODUCTION: Although fecal microbiota transplantation (FMT) is a recommended, clinically efficacious, and cost-effective treatment for recurrent Clostridioides difficile infection (CDI), the scale of FMT use in the United States is unknown.<br><br>METHODS: We developed a population-level CDI model.<br><br>RESULTS: We estimated that 48,000 FMTs could be performed annually, preventing 32,000 CDI recurrences.<br><br>DISCUSSION: Improving access to FMT could lead to tens of thousands fewer C. difficile episodes per year.}, }
@article {pmid33256346, year = {2020}, author = {He, Z and Ye, F and Zhang, GX}, title = {[Advances of fecal microbiota transplantation in improving the prognosis of cancer patients].}, journal = {Zhonghua nei ke za zhi}, volume = {59}, number = {12}, pages = {1003-1008}, doi = {10.3760/cma.j.cn112138-20200305-00189}, pmid = {33256346}, issn = {0578-1426}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Neoplasms/therapy ; Prognosis ; Treatment Outcome ; }, }
@article {pmid33255588, year = {2020}, author = {Ballini, A and Scacco, S and Boccellino, M and Santacroce, L and Arrigoni, R}, title = {Microbiota and Obesity: Where Are We Now?.}, journal = {Biology}, volume = {9}, number = {12}, pages = {}, pmid = {33255588}, issn = {2079-7737}, abstract = {Genetic and environmental factors are underlying causes of obesity and other metabolic diseases, so it is therefore difficult to find suitable and effective medical treatments. However, without a doubt, the gut microbiota-and also the bacteria present in the oral cavity-act as key factors in the development of these pathologies, yet the mechanisms have not been fully described. Certainly, a more detailed knowledge of the structure of the microbiota-composition, intra- and inter-species relationships, metabolic functions-could be of great help in counteracting the onset of obesity. Identifying key bacterial species will allow us to create a database of "healthy" bacteria, making it possible to manipulate the bacterial community according to metabolic and clinical needs. Targeting gut microbiota in clinical care as treatment for obesity and health-related complications-even just for weight loss has become a real possibility. In this topical review we provide an overview of the role of the microbiota on host energy homeostasis and obesity-related metabolic diseases, therefore addressing the therapeutic potential of novel and existing strategies (impact of nutrition/dietary modulation, and fecal microbiota transplantation) in the treatment of metabolic disease.}, }
@article {pmid33255454, year = {2020}, author = {Barba, C and Soulage, CO and Caggiano, G and Glorieux, G and Fouque, D and Koppe, L}, title = {Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD.}, journal = {Toxins}, volume = {12}, number = {12}, pages = {}, pmid = {33255454}, issn = {2072-6651}, mesh = {Animals ; Biomarkers/metabolism ; DNA, Bacterial ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Glucose Intolerance/complications/therapy ; Kidney/metabolism ; Male ; Metabolic Diseases/metabolism/therapy ; Metabolome ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; Renal Insufficiency, Chronic/*metabolism/*therapy ; Uremia/*therapy ; Urine/chemistry ; }, abstract = {BACKGROUND: Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD.<br><br>METHODS: Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation.<br><br>RESULTS: Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function.<br><br>CONCLUSIONS: These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients.}, }
@article {pmid33254107, year = {2020}, author = {Waldbaum, C and López, F and Antelo, P and Sorda, J}, title = {[Faecal microbiota transplantation for Clostridioides difficile infection].}, journal = {Medicina}, volume = {80}, number = {6}, pages = {633-639}, pmid = {33254107}, issn = {1669-9106}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridiodes difficile infection (CDi) is the most common cause of nosocomial diarrhea. Vancomycin, associated or not to metronidazol, is the treatment of choice. However, the rate of treatment failure has increased over the last years and fecal microbiota transplantation (FMT) has emerged as a therapeutic option. To evaluate safety and efficacy of FMT were enrolled 21 hospitalized patients with refractory or recurrent CDi between 2016 and 2019. Fourteen (66%) patients were men and the average age was 76.5 years (range 33-92). Ten had recurrent and 11 refractory CDi, and 18 presented severe and 3 fulminant clinical forms. In 20 cases the FMT was delivered through a nasojejunal tube and in one patient with ileo via enema infusion. Frozen fecal from a stool bank were administered in 20 and in the remaining was used fresh fecal matter. The rate of resolution was observed in 20 patients (95.2%) and none presented recurrence. The response rate was similar in recurrent or refractory forms (9/10 vs 11/11 respectively). One patient with osteomyelitis and multiple organ failure received 2 FMT without response and died. Seven patients (31%) presented mild and self-limited adverse effects. FMT has shown a high efficacy as rescue treatment in cases with refractory or recurrent CDi regardless of severity, with mild side effects. Availability of a stool banks provide reliable, timely and equitable access to FMT for CDi.}, }
@article {pmid33253686, year = {2021}, author = {Acharya, C and Bajaj, JS}, title = {Chronic Liver Diseases and the Microbiome-Translating Our Knowledge of Gut Microbiota to Management of Chronic Liver Disease.}, journal = {Gastroenterology}, volume = {160}, number = {2}, pages = {556-572}, pmid = {33253686}, issn = {1528-0012}, support = {R21 TR003095/TR/NCATS NIH HHS/United States ; R01 HS025412/HS/AHRQ HHS/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; I01 CX000176/CX/CSRD VA/United States ; I01 CX001076/CX/CSRD VA/United States ; }, mesh = {Animals ; Brain/microbiology/physiopathology ; Chronic Disease ; Diet ; Disease Models, Animal ; Disease Progression ; Dysbiosis/etiology/microbiology/physiopathology/therapy ; End Stage Liver Disease/etiology/microbiology/prevention &amp; control/therapy ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Liver Diseases/etiology/*microbiology/prevention &amp; control/therapy ; }, abstract = {Chronic liver disease is reaching epidemic proportions with the increasing prevalence of obesity, nonalcoholic liver disease, and alcohol overuse worldwide. Most patients are not candidates for liver transplantation even if they have end-stage liver disease. There is growing evidence of a gut microbial basis for many liver diseases, therefore, better diagnostic, prognostic, and therapeutic approaches based on knowledge of gut microbiota are needed. We review the questions that need to be answered to successfully translate our knowledge of the intestinal microbiome and the changes associated with liver disease into practice.}, }
@article {pmid33253683, year = {2021}, author = {Cook, L and Rees, WD and Wong, MQ and Kwok, WW and Levings, MK and Steiner, TS}, title = {Recurrent Clostridioides difficile Infection Is Associated With Impaired T Helper Type 17 Immunity to C difficile Toxin B.}, journal = {Gastroenterology}, volume = {160}, number = {4}, pages = {1410-1413.e4}, doi = {10.1053/j.gastro.2020.11.043}, pmid = {33253683}, issn = {1528-0012}, support = {20R76508//CIHR/Canada ; 20R75988//CIHR/Canada ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins/*immunology ; Bacterial Toxins/*immunology ; Case-Control Studies ; Clostridioides difficile/*immunology/isolation &amp; purification ; Clostridium Infections/*immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Female ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; Recurrence ; Th17 Cells/*immunology ; Young Adult ; }, }
@article {pmid33253681, year = {2021}, author = {Lee, M and Chang, EB}, title = {Inflammatory Bowel Diseases (IBD) and the Microbiome-Searching the Crime Scene for Clues.}, journal = {Gastroenterology}, volume = {160}, number = {2}, pages = {524-537}, pmid = {33253681}, issn = {1528-0012}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DK113788/DK/NIDDK NIH HHS/United States ; RC2 DK122394/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; R01 DK047722/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Diet ; Disease Models, Animal ; Dysbiosis/genetics/immunology/*microbiology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/immunology/*physiology ; Humans ; Inflammatory Bowel Diseases/genetics/immunology/*microbiology/therapy ; Mice ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {Inflammatory bowel diseases (IBD) develop via convergence of environmental, microbial, immunological, and genetic factors. Alterations in the gut microbiota have been associated with development and progression of IBD, but it is not clear which populations of microbes are involved or how they might contribute to IBD. We review the genetic and environmental factors affecting the gut microbiota, the roles of gut microbes and their bioproducts in the development and clinical course of IBD, and strategies by which microbiome-based therapies can be used to prevent, manage, and eventually cure IBD. We discuss research findings that help bridge the gap between the basic sciences and clinical application.}, }
@article {pmid33249800, year = {2021}, author = {Sehgal, K and Khanna, S}, title = {Gut microbiome and checkpoint inhibitor colitis.}, journal = {Intestinal research}, volume = {19}, number = {4}, pages = {360-364}, pmid = {33249800}, issn = {1598-9100}, abstract = {Immune checkpoint inhibitor therapies such as ipilimumab, are increasingly being used as a treatment option for a variety of cancers, including metastatic melanoma and have demonstrated effectively a prolonged survival. These agents have an immunological mode of action that predisposes patients to a number of immune-related adverse events, colitis being one of the most commonly encountered complications. The pathogenesis for the development of colitis is unclear, and there is a growing consensus that the ecosystem of the gastrointestinal microbiota plays a significant role. Based on this suspected connection, studies are being carried out to explore the changes in the microbiota in patients on these medications who develop colitis. Conceivably, the modulation of the gut microbiota could offer a therapeutic benefit. Fecal microbiota transplantation is one therapeutic option that is currently being investigated, though there are still more data needed to evaluate its efficacy. In this review, we recapitulate the mechanisms of action of immune checkpoint inhibitors, their adverse events, with a focus on colitis and the role gut microbiota are suspected to play, and finally discuss the microbiota modulation therapies being investigated.}, }
@article {pmid33246175, year = {2021}, author = {Doifode, T and Giridharan, VV and Generoso, JS and Bhatti, G and Collodel, A and Schulz, PE and Forlenza, OV and Barichello, T}, title = {The impact of the microbiota-gut-brain axis on Alzheimer's disease pathophysiology.}, journal = {Pharmacological research}, volume = {164}, number = {}, pages = {105314}, doi = {10.1016/j.phrs.2020.105314}, pmid = {33246175}, issn = {1096-1186}, mesh = {Alzheimer Disease/*microbiology ; Animals ; *Brain ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {The gut microbiota is a complex ecosystem that comprises of more than 100 trillion symbiotic microbial cells. The microbiota, the gut, and the brain form an association, 'the microbiota-gut-brain axis,' and synchronize the gut with the central nervous system and modify the behavior and brain immune homeostasis. The bidirectional communication between gut and brain occurs via the immune system, the vagus nerve, the enteric nervous system, and microbial metabolites, including short-chain fatty acids (SCFAs), proteins, and tryptophan metabolites. Recent studies have implicated the gut microbiota in many neurodegenerative diseases, including Alzheimer's disease (AD). In this review, we present an overview of gut microbiota, including Firmicutes, Bacteroidetes, SCFA, tryptophan, bacterial composition, besides age-related changes in gut microbiota composition, the microbiota-gut-brain axis pathways, the role of gut metabolites in amyloid-beta clearance, and gut microbiota modulation from experimental and clinical AD models. Understanding the role of the microbiota may provide new targets for treatment to delay the onset, progression, or reverse AD, and may help in reducing the prevalence of AD.}, }
@article {pmid33245014, year = {2020}, author = {Srivastava, V and Deblais, L and Huang, HC and Miyazaki, A and Kandasamy, S and Langel, SN and Paim, FC and Chepngeno, J and Kathayat, D and Vlasova, AN and Saif, LJ and Rajashekara, G}, title = {Reduced rotavirus vaccine efficacy in protein malnourished human-faecal-microbiota-transplanted gnotobiotic pig model is in part attributed to the gut microbiota.}, journal = {Beneficial microbes}, volume = {11}, number = {8}, pages = {733-751}, doi = {10.3920/BM2019.0139}, pmid = {33245014}, issn = {1876-2891}, mesh = {Animals ; Bacteria/classification ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Chlorocebus aethiops ; Cytokines/blood ; Diet ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastroenteritis/prevention &amp; control/veterinary/virology ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Humans ; Intestines/microbiology ; Malnutrition/immunology/*physiopathology ; Rotavirus/*immunology ; Rotavirus Infections/immunology/prevention &amp; control/*veterinary ; Rotavirus Vaccines/*immunology ; Swine ; Swine Diseases/immunology/prevention &amp; control ; *Vaccine Potency ; }, abstract = {The low efficacy of human rotavirus (HRV) vaccines in low- and middle-income countries (LMIC) remains a major challenge for global health. Protein-calorie malnutrition (kwashiorkor) affects the gut microbiota and compromises immune development, leading to environmental enteropathy, vaccine failures, and increased susceptibility to enteric diseases in young children. Relationship between diet and reduced vaccine efficacy in developing countries is not well established; therefore, we investigated the interconnections between the host-microbiota-nutrition-HRV vaccine using HRV-vaccinated, human infant faecal microbiota (HIFM)-transplanted neonatal gnotobiotic pigs fed with a protein deficient or sufficient diet. The microbiota from faecal, intestinal (duodenum, ileum, jejunum, and colon), and systemic tissue (liver, spleen, and mesenteric lymph node [MLN]) samples was analysed before and after HRV challenge using MiSeq 16S rRNA sequencing. Overall, microbiota from deficient fed HIFM pigs displayed, compared to the sufficient group, significantly higher Shannon index, especially in the faeces and lower intestines; higher level of Proteus and Enterococcus, and lower level of Bifidobacterium, Clostridium, and Streptococcus in the three types of samples collected (P<0.05); and higher unique operational taxonomic units (OTUs), especially in the systemic tissues. Further, the multivariate analysis between microbiota and immunologic data showed that 38 OTUs at the genus level correlated (r[2]≤0.5 or ≥-0.5; P<0.05) with at least one host immune response parameter (regulatory [Tregs and transforming growth factor-β], effectors [interferon (IFN)-γ[+] CD4[+] and CD8[+] T cells, IFN-γ and interleukin (IL)-12], and inflammatory [tumour necrosis factor-α, IL-17 and IL-22]) and with opposite trends between diet groups. Differences described above were increased after HRV challenge. We demonstrated that a protein deficient diet affects the composition of the gut microbiota and those changes may further correlate with immune responses induced by HRV and perturbed by the deficient diet. Thus, our findings suggest that the reduced efficacy of HRV vaccine observed in Gn pig model is in part attributed to the altered microbiota composition.}, }
@article {pmid33243141, year = {2020}, author = {Dang, XF and Qing-Xi Wang,  and Yin, Z and Sun, L and Yang, WH}, title = {Recurrence of moderate to severe ulcerative colitis after fecal microbiota transplantation treatment and the efficacy of re-FMT: a case series.}, journal = {BMC gastroenterology}, volume = {20}, number = {1}, pages = {401}, pmid = {33243141}, issn = {1471-230X}, mesh = {Adult ; *Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation ; Feces ; Female ; Humans ; *Inflammatory Bowel Diseases ; Male ; Middle Aged ; Recurrence ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), the pathogenesis of which is complicated, and it is difficult to treat. In recent years, the emerging fecal microbiota transplantation (FMT) has shown good effects in UC treatment and is therefore accepted by increasing numbers of patients. Our hospital has carried out FMT since 2017, and has achieved good results in UC treatment. We have found in our clinical work that the efficacy of re-FMT after recurrence decreased. This is difference from reported literatures. In order to attract clinical attention, here we selected typical cases for analysis.<br><br>METHODS: Among all UC patients who received FMT in our hospital, 12 patients with moderate to severe UC were selected. They all received multiple FMT and were followed up for 52&#x2009;weeks. Besides, none of them had other underlying diseases. Colonoscopy images of patients were presentated, SCCAI and UCDAI were used assess the effect of FMT.<br><br>RESULTS: On the whole, FMT has a significant effect on moderate to severe UC. Of the 12 patients, 11 (91.7%) achieved a clinical response, 9 (75.0%) achieved clinical remission, and only one patient did not respond to FMT treatment. However, 6 patients relapsed within 52&#x2009;weeks after remission, with a recurrence rate of 54.5%. Four of the six relapsed patients received FMT again, but the efficacy of FMT after relapse was significantly lower than that of the initial FMT. Fortunately, compared to before the initial FMT treatment, the severity of the disease after relapse was significantly reduced.<br><br>CONCLUSION: FMT has a good effect on the relief of moderate to severe UC. However, the effect of FMT treatment after relapse is reduced. For patients who relapse after remission, the efficacy of FMT reapplication requires more experiments to verify.}, }
@article {pmid33242652, year = {2021}, author = {Sun, N and Hu, H and Wang, F and Li, L and Zhu, W and Shen, Y and Xiu, J and Xu, Q}, title = {Antibiotic-induced microbiome depletion in adult mice disrupts blood-brain barrier and facilitates brain infiltration of monocytes after bone-marrow transplantation.}, journal = {Brain, behavior, and immunity}, volume = {92}, number = {}, pages = {102-114}, doi = {10.1016/j.bbi.2020.11.032}, pmid = {33242652}, issn = {1090-2139}, mesh = {Animals ; Anti-Bacterial Agents ; Blood-Brain Barrier ; Bone Marrow ; Bone Marrow Transplantation ; Brain ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; *Microbiota ; *Monocytes ; }, abstract = {The crosstalk between intestinal bacteria and the central nervous system, so called "the gut-brain axis", is critically important for maintaining brain homeostasis and function. This study aimed to investigate the integrity of the blood-brain barrier (BBB) and migration of bone marrow (BM)-derived cells to the brain parenchyma after intestinal microbiota depletion in adult mice. Gut microbiota dysbiosis was induced with 5 non-absorbable antibiotics in drinking water in mice that had received bone marrow transplantation (BMT) from green fluorescent protein (GFP) transgenic mice. Antibiotic-induced microbiome depletion reduced expression of tight-junction proteins of the brain blood vessels and increased BBB permeability. Fecal microbiota transplantation of antibiotics treated mice with pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. The BM-derived GFP[+] cells were observed to infiltrate specific brain regions, including the nucleus accumbens (NAc), the septal nucleus (SPT) and the hippocampus (CA3). The infiltrated cells acquired a ramified microglia-like morphology and Iba1, a microglia marker, was expressed in all GFP[+] cells, whereas they were negative for the astrocyte marker GFAP. Furthermore, treatment with CCR2 antagonist (RS102895) suppressed the recruitment of BM-derived monocytes to the brain. We report for the first time the migration of BM-derived monocytes to the brain regions involved in regulating emotional behaviors after depletion of intestinal microbiota in BMT background mice. However, mechanisms responsible for the migration and functions of the microglia-like infiltrated cells in the brain need further investigation. These findings indicate that monocyte recruitment to the brain in response to gut microbiota dysbiosis may represent a novel cellular mechanism that contributes to the development of brain disorders.}, }
@article {pmid33241758, year = {2021}, author = {Angelico, R and Liccardo, D and Paoletti, M and Pietrobattista, A and Basso, MS and Mosca, A and Safarikia, S and Grimaldi, C and Saffioti, MC and Candusso, M and Maggiore, G and Spada, M}, title = {A novel mobile phone application for infant stool color recognition: An easy and effective tool to identify acholic stools in newborns.}, journal = {Journal of medical screening}, volume = {28}, number = {3}, pages = {230-237}, doi = {10.1177/0969141320974413}, pmid = {33241758}, issn = {1475-5793}, mesh = {*Biliary Atresia ; *Cell Phone ; Child ; Color ; Feces ; Humans ; Infant ; Infant, Newborn ; *Mobile Applications ; }, abstract = {OBJECTIVES: Early diagnosis of biliary atresia is essential to improve long-term outcomes. Newborn screening with an infant stool color card allows early recognition of biliary atresia patients. Our aim was to develop and validate a mobile phone application (PopòApp) able to identify acholic stools.<br><br>METHODS: An intuitive app was developed for iOS and Android smartphones. A learning machine process was used to generate an algorithm for stools color recognition based on the seven colors of the infant stool color card, which were considered as the gold standard. Consecutive images of stools were taken by the Pop&#xf2;App, directly into the diapers of children aged &#x2264;6&#x2009;months. The Pop&#xf2;App classified the photographs as "normal", "acholic" or "uncertain". To validate the Pop&#xf2;App, four doctors independently classified all images, and only those for which all doctors agreed were included. The sensitivity, specificity, positive/negative predictive values, and accuracy of the Pop&#xf2;App were evaluated.<br><br>RESULTS: Of 165 images collected, 160 were included in the study. All acholic stools were recognized by the Pop&#xf2;App. The Pop&#xf2;App sensitivity was 100% (95% CI:93.9%-100%) with no false negatives, regardless of the brand of phone. The specificity was 99.0% (95% CI:94.6%-99.9%). The accurancy of the Pop&#xf2;App was 99.4% (95% CI:96.6%-99.9%), with a positive predictive value of 98.4% (95% CI:89.8%-99.8%).<br><br>CONCLUSION: The current study proved, in a large cohort, that the Pop&#xf2;App is an accurate and easy tool for recognition of acholic stools. The mobile App may represent an effective strategy for the early referral of children with acholic stools, and potentially could improve the outcomes of biliary atresia.}, }
@article {pmid33241674, year = {2021}, author = {Henig, I and Yehudai-Ofir, D and Zuckerman, T}, title = {The clinical role of the gut microbiome and fecal microbiota transplantation in allogeneic stem cell transplantation.}, journal = {Haematologica}, volume = {106}, number = {4}, pages = {933-946}, pmid = {33241674}, issn = {1592-8721}, mesh = {Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Transplantation, Homologous ; }, abstract = {Outcomes of allogeneic hematopoietic stem cell transplantation (allo- HSCT) have improved in the recent decade; however, infections and graft-versus-host disease remain two leading complications significantly contributing to early transplant-related mortality. In past years, the human intestinal microbial composition (microbiota) has been found to be associated with various disease states, including cancer, response to cancer immunotherapy and to modulate the gut innate and adaptive immune response. In the setting of allo-HSCT, the intestinal microbiota diversity and composition appear to have an impact on infection risk, mortality and overall survival. Microbial metabolites have been shown to contribute to the health and integrity of intestinal epithelial cells during inflammation, thus mitigating graft-versus-host disease in animal models. While the cause-andeffect relationship between the intestinal microbiota and transplant-associated complications has not yet been fully elucidated, the above findings have already resulted in the implementation of various interventions aiming to restore the intestinal microbiota diversity and composition. Among others, these interventions include the administration of fecal microbiota transplantation. The present review, based on published data, is intended to define the role of the latter approach in the setting of allo-HSCT.}, }
@article {pmid33241161, year = {2020}, author = {Olesen, SW}, title = {Power calculations for detecting differences in efficacy of fecal microbiota donors.}, journal = {Contemporary clinical trials communications}, volume = {20}, number = {}, pages = {100674}, pmid = {33241161}, issn = {2451-8654}, abstract = {Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of other indications, notably inflammatory bowel disease. The immense variability in human stool, combined with anecdotal reports from FMT studies, have suggested the existence of "donor effects", in which stool from some FMT donors is more efficacious than stool from other donors. In this study, simulated clinical trials were used to estimate the number of patients that would be required to detect donor effects under a variety of study designs. In most cases, reliable detection of donor effects required more than 100 patients treated with FMT. These results suggest that previous reports of donor effects need to be verified with results from large clinical trials and that patient biomarkers may be the most promising route to robustly identifying donor effects.}, }
@article {pmid33239790, year = {2020}, author = {Schluter, J and Peled, JU and Taylor, BP and Markey, KA and Smith, M and Taur, Y and Niehus, R and Staffas, A and Dai, A and Fontana, E and Amoretti, LA and Wright, RJ and Morjaria, S and Fenelus, M and Pessin, MS and Chao, NJ and Lew, M and Bohannon, L and Bush, A and Sung, AD and Hohl, TM and Perales, MA and van den Brink, MRM and Xavier, JB}, title = {The gut microbiota is associated with immune cell dynamics in humans.}, journal = {Nature}, volume = {588}, number = {7837}, pages = {303-307}, pmid = {33239790}, issn = {1476-4687}, support = {/WT_/Wellcome Trust/United Kingdom ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI093808/AI/NIAID NIH HHS/United States ; U54 CA209975/CA/NCI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 CA203950/CA/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Bayes Theorem ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Humans ; Leukocyte Count ; Leukocytes/*cytology/*immunology ; Lymphocytes/cytology/immunology ; Monocytes/cytology/immunology ; Neutrophils/cytology/immunology ; Reproducibility of Results ; }, abstract = {The gut microbiota influences development[1-3] and homeostasis[4-7] of the mammalian immune system, and is associated with human inflammatory[8] and immune diseases[9,10] as well as responses to immunotherapy[11-14]. Nevertheless, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans, where the difficulty of direct experimentation makes inference challenging. Here we study hundreds of hospitalized-and closely monitored-patients with cancer receiving haematopoietic cell transplantation as they recover from chemotherapy and stem-cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, enabling the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and more than 10,000 longitudinal microbiota samples revealed consistent associations between gut bacteria and immune cell dynamics. High-resolution clinical metadata and Bayesian inference allowed us to compare the effects of bacterial genera in relation to those of immunomodulatory medications, revealing a considerable influence of the gut microbiota-together and over time-on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.}, }
@article {pmid33239339, year = {2021}, author = {Ianiro, G and Gasbarrini, A and Cammarota, G}, title = {Autologous faecal microbiota transplantation for type 1 diabetes: a potential mindshift in therapeutic microbiome manipulation?.}, journal = {Gut}, volume = {70}, number = {1}, pages = {2-3}, doi = {10.1136/gutjnl-2020-323252}, pmid = {33239339}, issn = {1468-3288}, mesh = {*Diabetes Mellitus, Type 1/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid33235890, year = {2020}, author = {Olesen, SW and Zaman, A and Osman, M and Ramakrishna, B}, title = {Modeling Donor Screening Strategies to Reduce the Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission via Fecal Microbiota Transplantation.}, journal = {Open forum infectious diseases}, volume = {7}, number = {11}, pages = {ofaa499}, pmid = {33235890}, issn = {2328-8957}, abstract = {The potential for transmission of severe acute respiratory syndrome coronavirus 2 shed in stool via fecal microbiota transplantation is not yet known, and the effectiveness of various testing strategies to prevent fecal microbiota transplantation-based transmission has also not yet been quantified. In this study, we use a mathematical model to simulate the utility of different testing strategies.}, }
@article {pmid33233042, year = {2020}, author = {Xi, M and Li, J and Hao, G and An, X and Song, Y and Wei, H and Ge, W}, title = {Stachyose increases intestinal barrier through Akkermansia muciniphila and reduces gut inflammation in germ-free mice after human fecal transplantation.}, journal = {Food research international (Ottawa, Ont.)}, volume = {137}, number = {}, pages = {109288}, doi = {10.1016/j.foodres.2020.109288}, pmid = {33233042}, issn = {1873-7145}, mesh = {*Akkermansia ; Animals ; *Fecal Microbiota Transplantation ; Humans ; Inflammation ; Mice ; Oligosaccharides ; Verrucomicrobia ; }, abstract = {Early life is a crucial period for the development of the intestinal microbiota and is related to the body's immunity. Yet research is lacking regarding the effect of stachyose on infants gut microbiomes at this stage and the mechanism is not clear. Therefore, in this experiment, feces samples collected from infants were transplanted into germ-free mice, to explore the effect of stachyose on the intestinal microbiota and host gut barrier. We found that stachyose promoted the relative abundance of A. muciniphila in human feces; enhanced the symbiotic relationships of A. muciniphila; increased the short-chain fatty acid level, and secretory immunoglobulin A level; reduced the levels of lipopolysaccharide, IL-1, IL-17 and TNF-α through downregulated the expression of NF-κB; increased expression of tight junction proteins (occludin and ZO-1) and goblet cell through A. muciniphila. The intake of stachyose is conducive to promoting the proliferation of beneficial bacteria and enhancing the intestinal barrier in germ-free mice. This research provides a theoretical basis for the use of prebiotics to improve intestinal microbiota and barrier in humans.}, }
@article {pmid33232785, year = {2021}, author = {Ait Chait, Y and Mottawea, W and Tompkins, TA and Hammami, R}, title = {Nutritional and therapeutic approaches for protecting human gut microbiota from psychotropic treatments.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {108}, number = {}, pages = {110182}, doi = {10.1016/j.pnpbp.2020.110182}, pmid = {33232785}, issn = {1878-4216}, mesh = {Dysbiosis/chemically induced/diet therapy/*prevention &amp; control ; Gastrointestinal Microbiome/*drug effects ; Humans ; *Nutrition Therapy/methods ; Psychotropic Drugs/*adverse effects ; }, abstract = {Emerging evidence highlighted the essential role played by the microbiota-gut-brain axis in maintaining human homeostasis, including nutrition, immunity, and metabolism. Much recent work has linked the gut microbiota to many psychiatric and neurodegenerative disorders such as depression, schizophrenia, and Alzheimer's disease. Shared gut microbiota alterations or dysbiotic microbiota have been identified in these separate disorders relative to controls. Much attention has focused on the bidirectional interplay between the gut microbiota and the brain, establishing gut dysbiotic status as a critical factor in psychiatric disorders. Still, the antibiotic-like effect of psychotropic drugs, medications used for the treatment of these disorders, on gut microbiota is largely neglected. In this review, we summarize the current findings on the impact of psychotropics on gut microbiota and how their antimicrobial potency can trigger dysbiosis. We also discuss the potential therapeutic strategies, including probiotics, prebiotics, and fecal transplantation, to attenuate the dysbiosis related to psychotropics intake.}, }
@article {pmid33231660, year = {2020}, author = {Slomski, A}, title = {Fecal Transplant for Clostridioides difficile Effective in Practice.}, journal = {JAMA}, volume = {324}, number = {20}, pages = {2020}, doi = {10.1001/jama.2020.22572}, pmid = {33231660}, issn = {1538-3598}, }
@article {pmid33230077, year = {2021}, author = {Popov, J and Hartung, E and Hill, L and Chauhan, U and Pai, N}, title = {Pediatric Patient and Parent Perceptions of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {73}, number = {6}, pages = {684-688}, doi = {10.1097/MPG.0000000000002995}, pmid = {33230077}, issn = {1536-4801}, mesh = {Child ; *Colitis, Ulcerative/etiology/therapy ; *Fecal Microbiota Transplantation/methods ; Feces ; Humans ; Parents ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has gained attention for its role in the treatment of ulcerative colitis (UC). Acceptance of this treatment, particularly among children and their parents, is an important aspect of assessing its feasibility for pediatric inflammatory bowel disease care. To date, no studies have assessed FMT acceptance among pediatric patients who underwent FMT treatment. Here, we explored the perceptions and experiences of FMT in a population of pediatric UC patients who participated in a recent FMT pilot randomized controlled trial.<br><br>METHODS: Children who received bi-weekly FMT treatments for 6 weeks through a clinical trial (NCT02606032) and their parents participated in face-to-face, semi-structured interviews led by study investigators. Interviews were audiotaped, transcribed, and analyzed using validated qualitative research methods.<br><br>RESULTS: Eight patients and eight parents were interviewed, with qualitative data summarized across four themes and 11 subthemes. The majority of participants perceived FMT as a "natural treatment" and cited lack of response to conventional medications and fear of medication side-effects as motivators for pursuing FMT. Pre-treatment, patients and parents expressed concerns regarding physical discomfort with FMT administration; post-treatment, most patients reported feeling "completely normal." Both patients and parents uniformly expressed interest in pursuing FMT again in the future if available. Convenience of medication therapies, and perceived naturality and efficacy of FMT were all endorsed.<br><br>CONCLUSIONS: This is the first study to describe pediatric and parent experiences receiving FMT. This information is valuable to develop and encourage future FMT trials involving children. Pre-treatment, concerns about FMT were common. Post-treatment, patients reported tolerance to FMT and a desire to continue receiving this therapy if available. Further trials of FMT in UC are needed. Investigators should include pediatric patients without concern of acceptance.}, }
@article {pmid33228099, year = {2020}, author = {Kang, M and Choe, D and Kim, K and Cho, BK and Cho, S}, title = {Synthetic Biology Approaches in The Development of Engineered Therapeutic Microbes.}, journal = {International journal of molecular sciences}, volume = {21}, number = {22}, pages = {}, pmid = {33228099}, issn = {1422-0067}, support = {2018M3A9H3024759//National Research Foundation of Korea/ ; 2018M3A9F3079664//National Research Foundation of Korea/ ; 2018R1A1A3A04079196//National Research Foundation of Korea/ ; }, mesh = {Animals ; Diabetes Mellitus/microbiology/pathology/*therapy ; Disease Models, Animal ; Dysbiosis/microbiology/pathology/*therapy ; Escherichia coli/genetics/metabolism ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Diseases/microbiology/pathology/*therapy ; Gastrointestinal Microbiome/genetics ; Gene Regulatory Networks ; Genetic Engineering/*methods ; Humans ; Lactococcus lactis/genetics/metabolism ; Mice ; Neoplasms/microbiology/pathology/*therapy ; Probiotics/therapeutic use ; Recombinant Proteins/genetics/metabolism ; Synthetic Biology/*methods ; }, abstract = {Since the intimate relationship between microbes and human health has been uncovered, microbes have been in the spotlight as therapeutic targets for several diseases. Microbes contribute to a wide range of diseases, such as gastrointestinal disorders, diabetes and cancer. However, as host-microbiome interactions have not been fully elucidated, treatments such as probiotic administration and fecal transplantations that are used to modulate the microbial community often cause nonspecific results with serious safety concerns. As an alternative, synthetic biology can be used to rewire microbial networks such that the microbes can function as therapeutic agents. Genetic sensors can be transformed to detect biomarkers associated with disease occurrence and progression. Moreover, microbes can be reprogrammed to produce various therapeutic molecules from the host and bacterial proteins, such as cytokines, enzymes and signaling molecules, in response to a disturbed physiological state of the host. These therapeutic treatment systems are composed of several genetic parts, either identified in bacterial endogenous regulation systems or developed through synthetic design. Such genetic components are connected to form complex genetic logic circuits for sophisticated therapy. In this review, we discussed the synthetic biology strategies that can be used to construct engineered therapeutic microbes for improved microbiome-based treatment.}, }
@article {pmid33227623, year = {2021}, author = {Araujo, DV and Watson, GA and Oliva, M and Heirali, A and Coburn, B and Spreafico, A and Siu, LL}, title = {Bugs as drugs: The role of microbiome in cancer focusing on immunotherapeutics.}, journal = {Cancer treatment reviews}, volume = {92}, number = {}, pages = {102125}, doi = {10.1016/j.ctrv.2020.102125}, pmid = {33227623}, issn = {1532-1967}, mesh = {Animals ; Gastrointestinal Microbiome/*physiology ; Humans ; Immunotherapy/*methods ; Mice ; Microbiota/*physiology ; Neoplasms/*drug therapy ; Prebiotics/*standards ; Probiotics/pharmacology/*therapeutic use ; }, abstract = {The human microbiome comprising microorganisms, their collective genomes and metabolic products has gained tremendous research interest in oncology, as multiple cohorts and case studies have demonstrated discernible interpatient differences in this ecosystem based on clinical variables including disease type, stage, diet, antibiotic usage, cancer treatments, therapeutic responses and toxicities. The modulation of the gut microbiome is the subject of many ongoing preclinical and clinical investigations, through the manipulation of diet, as well as the use of prebiotics, probiotics, specific antibiotics, fecal microbial transplantation, microbial consortia and stool substitutes. Standardization and quality control are needed to maximize the information being generated in this growing field, ranging from technical assays to measure microbiome composition, to methodological aspects in the analysis and reporting of results. Proof-of-mechanism and proof-of-concept clinical trials with appropriate controls are needed to confirm or refute the feasibility, safety and ultimately the clinical utility of human microbiome modulation in cancer patients.}, }
@article {pmid33227280, year = {2021}, author = {Randel, KR and Schult, AL and Botteri, E and Hoff, G and Bretthauer, M and Ursin, G and Natvig, E and Berstad, P and Jørgensen, A and Sandvei, PK and Olsen, ME and Frigstad, SO and Darre-Næss, O and Norvard, ER and Bolstad, N and Kørner, H and Wibe, A and Wensaas, KA and de Lange, T and Holme, &#xd8;}, title = {Colorectal Cancer Screening With Repeated Fecal Immunochemical Test Versus Sigmoidoscopy: Baseline Results From a Randomized Trial.}, journal = {Gastroenterology}, volume = {160}, number = {4}, pages = {1085-1096.e5}, doi = {10.1053/j.gastro.2020.11.037}, pmid = {33227280}, issn = {1528-0012}, mesh = {Aged ; Colonoscopy/statistics &amp; numerical data ; Colorectal Neoplasms/*diagnosis/epidemiology ; Early Detection of Cancer/*methods/statistics &amp; numerical data ; Female ; Humans ; Male ; Mass Screening/*methods/statistics &amp; numerical data ; Middle Aged ; Norway/epidemiology ; *Occult Blood ; Odds Ratio ; Pilot Projects ; Sigmoidoscopy/*statistics &amp; numerical data ; }, abstract = {BACKGROUND &amp; AIMS: The comparative effectiveness of sigmoidoscopy and fecal immunochemical testing (FIT) for colorectal cancer (CRC) screening is unknown.<br><br>METHODS: Individuals aged 50-74 years living in Southeast Norway were randomly invited between 2012 and 2019 to either once-only flexible sigmoidoscopy or FIT screening every second year. Colonoscopy was recommended after sigmoidoscopy if any polyp of &#x2265;10&#x2009;mm, &#x2265;3 adenomas, any advanced adenomas, or CRC was found or, subsequent to, FIT >15&#x2009;&#x3bc;g hemoglobin/g&#x2009;feces. Data for this report were obtained after complete recruitment in both groups and included 2 full FIT rounds and part of the third round. Outcome measures were participation, neoplasia detection, and adverse events. Age-standardized detection rates and age-adjusted odds ratios (ORs) were calculated.<br><br>RESULTS: We included 139,291 individuals: 69,195 randomized to sigmoidoscopy and 70,096 to FIT. The participation rate was 52% for sigmoidoscopy, 58% in the first FIT round, and 68% for 3 cumulative FIT rounds. Compared to sigmoidoscopy, the detection rate for CRC was similar in the first FIT round (0.25% vs 0.27%; OR, 0.92; 95% confidence interval&#x2009;[CI], 0.75-1.13) but higher after 3 FIT rounds (0.49% vs 0.27%; OR, 1.87; 95%&#x2009;CI, 1.54-2.27). Advanced adenoma detection rate was lower in the first FIT round compared to sigmoidoscopy at 1.4% vs 2.4%&#x2009;(OR, 0.57; 95%&#x2009;CI, 0.53-0.62) but higher after 3 cumulative FIT rounds at 2.7% vs 2.4%&#x2009;(OR, 1.14; 95%&#x2009;CI, 1.05-1.23). There were 33 (0.05%) serious adverse events in the sigmoidoscopy group compared to 47 (0.07%) in the FIT group (P&#x2009;= .13).<br><br>CONCLUSIONS: Participation was higher and more CRC and advanced adenomas were detected with repeated FIT compared to sigmoidoscopy. The risk of perforation and bleeding was comparable. Clinicaltrials.gov, Number: NCT01538550.}, }
@article {pmid33225985, year = {2020}, author = {Huang, H and Ren, Z and Gao, X and Hu, X and Zhou, Y and Jiang, J and Lu, H and Yin, S and Ji, J and Zhou, L and Zheng, S}, title = {Integrated analysis of microbiome and host transcriptome reveals correlations between gut microbiota and clinical outcomes in HBV-related hepatocellular carcinoma.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {102}, pmid = {33225985}, issn = {1756-994X}, mesh = {Adult ; Aged ; Bacteria/classification/genetics ; Biomarkers, Tumor ; Carcinoma, Hepatocellular/*genetics/*metabolism ; Computational Biology ; Feces ; *Gastrointestinal Microbiome/genetics ; Gene Expression Regulation, Neoplastic ; Hepatitis B virus ; Host Microbial Interactions ; Humans ; Liver/metabolism ; Liver Neoplasms/*genetics/*metabolism ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; *Transcriptome ; }, abstract = {BACKGROUND: The gut-liver axis plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC). However, the correlations between the gut microbiome and the liver tumor transcriptome in patients with HCC and the impact of the gut microbiota on clinical outcome are less well-understood.<br><br>METHODS: Fecal samples collected from HBV-related HCC patients (n&#x2009;=&#x2009;113) and healthy volunteers (n&#x2009;=&#x2009;100) were subjected to 16S rRNA sequencing of the microbiome. After a rigorous selection process, 32 paired tumor and adjacent non-tumor liver tissues from the HCC group were subjected to next-generation sequencing (NGS) RNA-seq. The datasets were analyzed individually and integrated with clinical characteristics for combined analysis using bioinformatics approaches. We further verified the potential of the gut microbiota to predict clinical outcome by a random forest model and a support vector machine model.<br><br>RESULTS: We found that Bacteroides, Lachnospiracea incertae sedis, and Clostridium XIVa were enriched in HCC patients with a high tumor burden. By integrating the microbiome and transcriptome, we identified 31 robust associations between the above three genera and well-characterized genes, indicating possible mechanistic relationships in tumor immune microenvironment. Clinical characteristics and database analysis suggested that serum bile acids may be important communication mediators between these three genera and the host transcriptome. Finally, among these three genera, six important microbial markers associated with tumor immune microenvironment or bile acid metabolism showed the potential to predict clinical outcome (AUC&#x2009;=&#x2009;81%).<br><br>CONCLUSIONS: This study revealed that changes in tumor immune microenvironment caused by the gut microbiota via serum bile acids may be important factors associated with tumor burden and adverse clinical outcome. Gut microbes can be used as biomarkers of clinical features and outcomes, and the microbe-associated transcripts of host tumors can partly explain how gut microbiota promotes HCC pathogenesis.}, }
@article {pmid33225575, year = {2021}, author = {Whon, TW and Kim, HS and Shin, NR and Jung, ES and Tak, EJ and Sung, H and Jung, MJ and Jeong, YS and Hyun, DW and Kim, PS and Jang, YK and Lee, CH and Bae, JW}, title = {Male castration increases adiposity via small intestinal microbial alterations.}, journal = {EMBO reports}, volume = {22}, number = {1}, pages = {e50663}, pmid = {33225575}, issn = {1469-3178}, mesh = {*Adiposity ; Animals ; Cattle ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Male ; Mice ; Obesity ; Orchiectomy ; }, abstract = {Castration of young males is widely used in the cattle industry to improve meat quality, but the mechanism linking hypogonadism and host metabolism is not clear. Here, we use metataxonomic and metabolomic approaches to evaluate the intestinal microbiota and host metabolism in male, castrated male (CtM), and female cattle. After pubescence, the CtM cattle harbor distinct ileal microbiota dominated by the family Peptostreptococcaceae and exhibit distinct serum and muscle amino acid profiles (i.e., highly abundant branched-chain amino acids), with increased extra- and intramuscular fat storage. We also evaluate the causative factor(s) that underpin the alteration of the intestinal microbiota and host metabolic phenotype in response to hypogonadism. Castration of male mice phenocopies both the intestinal microbial alterations and obese-prone metabolism observed in cattle. Antibiotic treatment and fecal microbiota transplantation experiments in a mouse model confirm that the intestinal microbial alterations associated with hypogonadism are a key contributor to the obese phenotype in the CtM animals. Collectively, targeting the gut microbiota is a potential therapeutic strategy for the treatment of both hypogonadism and obesity.}, }
@article {pmid33223509, year = {2020}, author = {Yu, F and Jiang, R and Han, W and Zhan, G and Xu, X and Jiang, X and Wang, L and Xiang, S and Zhou, Q and Liu, C and Zhu, B and Hua, F and Yang, C}, title = {Gut microbiota transplantation from db/db mice induces diabetes-like phenotypes and alterations in Hippo signaling in pseudo germ-free mice.}, journal = {Aging}, volume = {12}, number = {23}, pages = {24156-24167}, pmid = {33223509}, issn = {1945-4589}, mesh = {Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Blood Glucose/metabolism ; Cell Cycle Proteins/metabolism ; Diabetes Mellitus, Type 2/metabolism/*microbiology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; Hepatocyte Growth Factor/metabolism ; Hippo Signaling Pathway ; Intestines/*microbiology ; Kidney/metabolism ; Liver/metabolism ; Male ; Mice ; Myocardium/metabolism ; Phenotype ; Phosphorylation ; Protein Serine-Threonine Kinases/*metabolism ; Proto-Oncogene Proteins/metabolism ; Signal Transduction ; YAP-Signaling Proteins ; }, abstract = {Type 2 diabetes mellitus (T2DM) is an age-related metabolic disease that is of increasing concern. Gut microbiota might have a critical role in the pathogenesis of T2DM. Additionally, Hippo signaling has been associated strongly with the progression of T2DM and the aging process. We adopted db/db male mice as a T2DM model, and the gut microbiota of db/db and m/m mice were transplanted successfully into pseudo germ-free mice. Furthermore, Hippo signaling, including mammalian sterile 20-like protein kinases 1 (MST1), large tumor suppressors 1 (LATS1), Yes-associated protein (YAP), and phosphorylation of YAP (p-YAP) in peripheral tissues were significantly altered and highly correlated with blood glucose in db/db mice. Interestingly, the host after gut microbiota transplantation from db/db mice showed decreased MST1 and LATS1 levels, and p-YAP/YAP ratio in the heart, liver, and kidney compared to those from m/m mice. Negative correlations between fasting blood glucose and Hippo signaling levels in selected peripheral tissues also were identified. These findings suggest that alterations in Hippo signaling in selected peripheral tissues may contribute to the development of T2DM, and that therapeutic interventions improving Hippo signaling by gut microbiota transplantation might be beneficial for the treatment of T2DM and other age-related metabolic diseases.}, }
@article {pmid33222603, year = {2020}, author = {Zhang, XY and Chen, J and Yi, K and Peng, L and Xie, J and Gou, X and Peng, T and Tang, L}, title = {Phlorizin ameliorates obesity-associated endotoxemia and insulin resistance in high-fat diet-fed mice by targeting the gut microbiota and intestinal barrier integrity.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1-18}, pmid = {33222603}, issn = {1949-0984}, mesh = {Animals ; Anti-Obesity Agents/*pharmacology ; Bacteria/classification/isolation &amp; purification ; Diet, High-Fat ; Dietary Supplements ; Endotoxemia/*drug therapy ; Fatty Acids, Volatile/biosynthesis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Insulin Resistance/*physiology ; Lipopolysaccharides/blood ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/pathology ; Phlorhizin/*pharmacology ; Phytochemicals/pharmacology ; Tight Junctions/*drug effects ; Weight Gain/drug effects ; }, abstract = {Phlorizin (PHZ) is one of phytonutrients in apples that contributes to the health-promoting effect implicated by the saying, 'an apple a day keeps the doctor away'. PHZ was firstly identified as a competitive inhibitor of sodium-glucose co-transporters-2 (SGLT2); however, its low bioavailability makes it hard to fully explain its pharmacological mechanisms. This study aimed to investigate the ameliorating effect of PHZ on high-fat diet (HFD)-induced obesity via modulating the "gut microbiota-barrier axis". Firstly, C57BL/6 J mice were fed a normal chow diet (NCD) or HFD coadministered with or without PHZ for 12 weeks. Our results showed that PHZ supplementation significantly reduced HFD-induced body weight gain (P < .001), alleviated metabolic disorders (MDs) like insulin resistance (P < .001) and elevation of serum lipopolysaccharides (LPS) (P < .001), attenuated HFD-induced gut microbiota alterations, enhanced short-chain fatty acids (SCFAs) production (P < .001), and inhibited fecal LPS production (P < .001). To investigate the role of the fecal microbiota in the observed beneficial effects, a fecal microbiota transplantation (FMT) experiment was performed by transplanting the feces of the four groups of mice (as donor mice) daily collected from the fourth week to a new batch of acclimatized HFD-fed mice. Our results confirmed that feeding the gut contents of the PHZ-modulated mice could attenuate HFD-induced MDs, accompanied by enhanced glucagon-like peptide 2 (GLP-2) secretion (P < .001) and restoration of HFD-induced damage in the gut epithelial barrier. This study has provided evidence that the "gut microbiota-barrier axis" was an alternative target for the anti-obesity effect of PHZ. This work has also provided an explanation for the high efficacy of PHZ despite the low bioavailability, and PHZ holds great potential to be developed as a functional food ingredient.}, }
@article {pmid33222240, year = {2021}, author = {Xi, M and Tang, H and Zhang, Y and Ge, W and Chen, Y and Cui, X}, title = {Microbiome-metabolomic analyses of the impacts of dietary stachyose on fecal microbiota and metabolites in infants intestinal microbiota-associated mice.}, journal = {Journal of the science of food and agriculture}, volume = {101}, number = {8}, pages = {3336-3347}, doi = {10.1002/jsfa.10963}, pmid = {33222240}, issn = {1097-0010}, support = {K4030217010//School-enterprise Cooperation Project/ ; 2017XY-02//Science and Technology Innovation as a Whole Plan Projects of Shaanxi Province/ ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification ; Chromatography, High Pressure Liquid ; Fecal Microbiota Transplantation ; Feces/chemistry/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Intestinal Mucosa/chemistry/metabolism/microbiology ; Male ; Metabolome ; Metabolomics ; Mice ; Oligosaccharides/*metabolism ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: The intestinal microbiota and metabolites play an important role in human health and immunity. However, few studies have investigated the long-term effects of stachyose on the human intestinal microbiota and metabolism. Therefore, in this study, the feces of infants were transplanted into germ-free mice, and the effect of long-term stachyose intake on intestinal metabolism was examined by comparing the results of microbiome and metabolome analyses. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to study the effects of stachyose intake on the metabolites and metabolic pathways of the transplanted human intestinal microbiota.<br><br>RESULTS: We observed that stachyose significantly altered the composition of the intestinal microbiota and metabolites, up-regulated production of the metabolite taurocholic acid, down-regulated amino acid metabolism, and significantly regulated the metabolism of taurine and hydroxytaurine, pantothenate and coenzyme A (CoA) biosynthesis, and other signaling pathways.<br><br>CONCLUSION: These findings may provide a basis for elucidating the mechanism by which stachyose promotes host health. &#xa9; 2020 Society of Chemical Industry.}, }
@article {pmid33222185, year = {2021}, author = {Turner, G and Smith, M and Hoeschen, AL and Wilson, JA and Kennedy, J and Abramson, M and Cao, Q and El Jurdi, N and MacMillan, ML and Weisdorf, DJ and Blazar, BR and Khoruts, A and Shields-Cutler, RR and Knights, D and Holtan, SG and Rashidi, A}, title = {Shotgun sequencing of the faecal microbiome to predict response to steroids in patients with lower gastrointestinal acute graft-versus-host disease: An exploratory analysis.}, journal = {British journal of haematology}, volume = {192}, number = {3}, pages = {e69-e73}, doi = {10.1111/bjh.17238}, pmid = {33222185}, issn = {1365-2141}, support = {P01 CA065493/CA/NCI NIH HHS/United States ; R37 AI034495/AI/NIAID NIH HHS/United States ; KL2 TR002492/TR/NCATS NIH HHS/United States ; }, mesh = {Acute Disease ; Bacteria/genetics/isolation &amp; purification ; Feces/*microbiology ; Graft vs Host Disease/diagnosis/*drug therapy/etiology/*microbiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/drug effects ; Prognosis ; Steroids/*therapeutic use ; }, }
@article {pmid33218339, year = {2020}, author = {Draper, LA and Ryan, FJ and Dalmasso, M and Casey, PG and McCann, A and Velayudhan, V and Ross, RP and Hill, C}, title = {Autochthonous faecal viral transfer (FVT) impacts the murine microbiome after antibiotic perturbation.}, journal = {BMC biology}, volume = {18}, number = {1}, pages = {173}, pmid = {33218339}, issn = {1741-7007}, support = {SFI/12/RC/2273/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage/*adverse effects ; Bacteria/drug effects/*isolation &amp; purification ; Bacterial Physiological Phenomena/*drug effects ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; *Metagenome ; Mice ; *Microbiota ; }, abstract = {BACKGROUND: It has become increasingly accepted that establishing and maintaining a complex and diverse gut microbiota is fundamental to human health. There are growing efforts to identify means of modulating and influencing the microbiota, especially in individuals who have experienced a disruption in their native microbiota. Faecal microbiota transplantation (FMT) is one method that restores diversity to the microbiota of an individual by introducing microbes from a healthy donor. FMT introduces the total microbial load into the recipient, including the bacteria, archaea, yeasts, protists and viruses. In this study, we investigated whether an autochthonous faecal viral transfer (FVT), in the form of a sterile faecal filtrate, could impact the recovery of a bacteriome disrupted by antibiotic treatment.<br><br>RESULTS: Following antibiotic disruption of the bacteriome, test mice received an FVT harvested prior to antibiotic treatment, while control mice received a heat- and nuclease-treated FVT. In both groups of mice, the perturbed microbiome reverted over time to one more similar to the pre-treatment one. However, the bacteriomes of mice that received an FVT, in which bacteriophages predominate, separated from those of the control mice as determined by principal co-ordinate analysis (PCoA). Moreover, analysis of the differentially abundant taxa indicated a closer resemblance to the pre-treatment bacteriome in the test mice that had received an FVT. Similarly, metagenomic sequencing of the virome confirmed that faecal bacteriophages of FVT and control mice differed over time in both abundance and diversity, with the phages constituting the FVT persisting in mice that received them.<br><br>CONCLUSIONS: An autochthonous virome transfer reshaped the bacteriomes of mice post-antibiotic treatment such that they more closely resembled the pre-antibiotic microbiota profile compared to mice that received non-viable phages. Thus, FVT may have a role in addressing antibiotic-associated microbiota alterations and potentially prevent the establishment of post-antibiotic infection. Given that bacteriophages are biologically inert in the absence of their host bacteria, they could form a safe and effective alternative to whole microbiota transplants that could be delivered during/following perturbation of the gut flora.}, }
@article {pmid33208178, year = {2020}, author = {Li, N and Zuo, B and Huang, S and Zeng, B and Han, D and Li, T and Liu, T and Wu, Z and Wei, H and Zhao, J and Wang, J}, title = {Spatial heterogeneity of bacterial colonization across different gut segments following inter-species microbiota transplantation.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {161}, pmid = {33208178}, issn = {2049-2618}, mesh = {Animals ; Bacteria/genetics/*isolation &amp; purification ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*anatomy &amp; histology/*microbiology ; Germ-Free Life ; Heterografts/*microbiology ; Mice ; Swine/*microbiology ; }, abstract = {BACKGROUND: The microbiota presents a compartmentalized distribution across different gut segments. Hence, the exogenous microbiota from a particular gut segment might only invade its homologous gut location during microbiota transplantation. Feces as the excreted residue contain most of the large-intestinal microbes but lack small-intestinal microbes. We speculated that whole-intestinal microbiota transplantation (WIMT), comprising jejunal, ileal, cecal, and colonic microbiota, would be more effective for reshaping the entire intestinal microbiota than conventional fecal microbiota transplantation fecal microbiota transplantation (FMT).<br><br>RESULTS: We modeled the compartmentalized colonization of the gut microbiota via transplanting the microbiota from jejunum, ileum, cecum, and colon, respectively, into the germ-free mice. Transplanting jejunal or ileal microbiota induced more exogenous microbes' colonization in the small intestine (SI) of germ-free mice rather than the large intestine (LI), primarily containing Proteobacteria, Lactobacillaceae, and Cyanobacteria. Conversely, more saccharolytic anaerobes from exogenous cecal or colonic microbiota, such as Bacteroidetes, Prevotellaceae, Lachnospiraceae, and Ruminococcaceae, established in the LI of germ-free mice that received corresponding intestinal segmented microbiota transplantation. Consistent compartmentalized colonization patterns of microbial functions in the intestine of germ-free mice were also observed. Genes related to nucleotide metabolism, genetic information processing, and replication and repair were primarily enriched in small-intestinal communities, whereas genes associated with the metabolism of essential nutrients such as carbohydrates, amino acids, cofactors, and vitamins were mainly enriched in large-intestinal communities of germ-free mice. Subsequently, we compared the difference in reshaping the community structure of germ-free mice between FMT and WIMT. FMT mainly transferred LI-derived microorganisms and gene functions into the recipient intestine with sparse SI-derived microbes successfully transplanted. However, WIMT introduced more SI-derived microbes and associated microbial functions to the recipient intestine than FMT. Besides, WIMT also improved intestinal morphological development as well as reduced systematic inflammation responses of recipients compared with FMT.<br><br>CONCLUSIONS: Segmented exogenous microbiota transplantation proved the spatial heterogeneity of bacterial colonization along the gastrointestinal tract, i.e., the microbiota from one specific location selectively colonizes its homologous gut region. Given the lack of exogenous small-intestinal microbes during FMT, WIMT may be a promising alternative for conventional FMT to reconstitute the microbiota across the entire intestinal tract. Video Abstract.}, }
@article {pmid33205871, year = {2020}, author = {Perttu, L and Jonna, J and Anna, H and Eero, M and Markku, H and Jari, P and Jari, K and Veli-Jukka, A and Jyrki, T and Reetta, S and Perttu, A}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-which improvements are required? Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {11-12}, pages = {1754-1755}, doi = {10.1111/apt.16122}, pmid = {33205871}, issn = {1365-2036}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid33205867, year = {2020}, author = {El-Salhy, M and Hausken, T and Gunnar Hatlebakk, J}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-which improvements are required?.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {11-12}, pages = {1752-1753}, doi = {10.1111/apt.16112}, pmid = {33205867}, issn = {1365-2036}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid33204401, year = {2020}, author = {Li, J and Han, J and Lv, J and Wang, S and Qu, L and Jiang, Y}, title = {Saikosaponin A-Induced Gut Microbiota Changes Attenuate Severe Acute Pancreatitis through the Activation of Keap1/Nrf2-ARE Antioxidant Signaling.}, journal = {Oxidative medicine and cellular longevity}, volume = {2020}, number = {}, pages = {9217219}, pmid = {33204401}, issn = {1942-0994}, mesh = {Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Antioxidant Response Elements ; Antioxidants/*metabolism ; Gastrointestinal Microbiome/*drug effects ; Kelch-Like ECH-Associated Protein 1/genetics/*metabolism ; Male ; NF-E2-Related Factor 2/genetics/*metabolism ; Oleanolic Acid/*analogs &amp; derivatives/pharmacology ; Oxidative Stress ; Pancreatitis/*drug therapy/metabolism/microbiology/pathology ; Rats ; Rats, Sprague-Dawley ; Saponins/*pharmacology ; Severity of Illness Index ; }, abstract = {OBJECTIVE: Severe acute pancreatitis (SAP) is a serious and life-threatening disease associated with multiple organ failure and a high mortality rate and is accompanied by distinct oxidative stress and inflammatory responses. Saikosaponin A has strong antioxidant properties and can affect the composition of gut microbiota. We sought to determine the effects of Saikosaponin A interventions on SAP by investigating the changes of gut microbiota and related antioxidant signaling.<br><br>METHODS: A SAP model was established in Sprague-Dawley (SD) rats through the injection of sodium taurocholate into the biliopancreatic duct and confirmed by elevated levels of serum lipase and amylase. The model was fed a standard diet either with saline solution or with Saikosaponin A. Fecal microbiota transplantation (FMT) from Saikosaponin A-induced rats into the rat model was performed to test the effects of gut microbiota. The composition of gut microbiota was analyzed by using 16S rRNA gene sequencing. We measured apoptotic status, inflammatory biomarkers, and Keap1-Nrf2-ARE ((Kelch-like ECH-associated protein 1) nuclear factor erythroid 2-related factor 2-antioxidant response element) antioxidant signaling.<br><br>RESULTS: Saikosaponin A intervention attenuated SAP lesions and reduced the levels of serum amylase and lipase, oxidative stress, and inflammatory responses by reducing pathological scores and affecting the serum level of oxidative and inflammatory factors. Meanwhile, the expression of Keap1-Nrf2-ARE was increased. Saikosaponin A intervention improved microbiota composition by increasing the relative abundance of Lactobacillus and Prevotella species. FMT resulted in similar results as those caused by the Saikosaponin A intervention, suggesting Saikosaponin A may exert its function via the improvement of gut microbiota composition.<br><br>CONCLUSIONS: Saikosaponin A-induced gut microbiota changes attenuate SAP progression in the rat model and may be a potential natural drug for adjuvant treatment of SAP. Further work is needed to clear up the points.}, }
@article {pmid33203880, year = {2020}, author = {Song, L and Liu, Z and Hu, HH and Yang, Y and Li, TY and Lin, ZZ and Ye, J and Chen, J and Huang, X and Liu, DT and Zhou, J and Shi, Y and Zhao, H and Xie, C and Chen, L and Song, E and Lin, SY and Lin, SC}, title = {Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5842}, pmid = {33203880}, issn = {2041-1723}, mesh = {Animals ; Breast Neoplasms/genetics/metabolism/mortality/*pathology ; CSK Tyrosine-Protein Kinase/*genetics/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Lipogenesis/physiology ; Mammary Neoplasms, Animal/genetics/pathology ; Mice, Mutant Strains ; Mice, Transgenic ; Phosphatidate Phosphatase/genetics/*metabolism ; Phosphorylation ; Proto-Oncogene Mas ; Tyrosine/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Increased lipogenesis has been linked to an increased cancer risk and poor prognosis; however, the underlying mechanisms remain obscure. Here we show that phosphatidic acid phosphatase (PAP) lipin-1, which generates diglyceride precursors necessary for the synthesis of glycerolipids, interacts with and is a direct substrate of the Src proto-oncogenic tyrosine kinase. Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride. Alteration of the three tyrosine residues to phenylalanine (3YF-lipin-1) disables lipin-1 from mediating Src-enhanced glycerolipid synthesis, cell proliferation and xenograft growth. Re-expression of 3YF-lipin-1 in PyVT;Lpin1[-/-] mice fails to promote progression and metastasis of mammary tumours. Human breast tumours exhibit increased p-Tyr-lipin-1 levels compared to the adjacent tissues. Importantly, statistical analyses show that levels of p-Tyr-lipin-1 correlate with tumour sizes, lymph node metastasis, time to recurrence and survival of the patients. These results illustrate a direct lipogenesis-promoting role of the pro-oncogenic Src, providing a mechanistic link between obesity-associated mitogenic signaling and breast cancer malignancy.}, }
@article {pmid33202167, year = {2021}, author = {Ducrocq, J and Simon, A and Lemire, M and De Serres, G and Lévesque, B}, title = {Exposure to Toxoplasma gondii Through Consumption of Raw or Undercooked Meat: A Systematic Review and Meta-Analysis.}, journal = {Vector borne and zoonotic diseases (Larchmont, N.Y.)}, volume = {21}, number = {1}, pages = {40-49}, doi = {10.1089/vbz.2020.2639}, pmid = {33202167}, issn = {1557-7759}, mesh = {Animals ; Antibodies, Protozoan/blood ; Cooking ; *Food Parasitology ; Humans ; Meat/*parasitology ; Prevalence ; Raw Foods/parasitology ; Seroepidemiologic Studies ; *Toxoplasma ; Toxoplasmosis/*transmission ; }, abstract = {Toxoplasma gondii is a globally distributed protozoan that mainly causes health issues in the fetuses of pregnant women who have never been exposed to this parasite and patients with deficient immune systems. Except in these vulnerable populations, the primary infection generally goes unnoticed in most healthy individuals. Apart from transplant/transfusion, congenital transmission, direct contact with infected cats or their feces, and environmental contamination (i.e., oocysts in food, water, and soil) pathways, humans can acquire the parasite through consumption of animal tissues infected by T. gondii. This meta-analysis estimated the risk of acquiring T. gondii by consuming raw or undercooked meat, regardless of which animal species are eaten. Using a random-effect model, crude and adjusted pooled measures of association (risk and odds ratio) were estimated according to study design (cohort, case-control, and cross-sectional studies). The meta-analysis included measures of heterogeneity as well as quality rating scales for each study design. Our results suggest that individuals who eat raw or undercooked meat have, respectively, 1.2-1.3 times the risk and 1.7-3.0 times the odds of T. gondii infection compared to those who thoroughly cook meat, regardless of the animal species they consume. These results align with the current understanding that adequately cooking meat inactivates the parasite and decreases the risk of transmission. Seroprevalence ranged from 1.3% to 88.6%, while the proportion of individuals eating raw or undercooked meat fluctuated from 0.7% to 98.3% across the studies in the meta-analysis. These numbers reflect various preferences with regard to eating meat (i.e., eating tartar, sausages, or salamis) as well as individual, cultural and religious food habits, and personal awareness.}, }
@article {pmid33198506, year = {2022}, author = {Duan, H and Yu, L and Tian, F and Zhai, Q and Fan, L and Chen, W}, title = {Antibiotic-induced gut dysbiosis and barrier disruption and the potential protective strategies.}, journal = {Critical reviews in food science and nutrition}, volume = {62}, number = {6}, pages = {1427-1452}, doi = {10.1080/10408398.2020.1843396}, pmid = {33198506}, issn = {1549-7852}, mesh = {Animals ; Anti-Bacterial Agents/toxicity ; Dysbiosis/chemically induced/prevention &amp; control ; *Gastrointestinal Microbiome ; Humans ; Lactobacillus ; *Probiotics ; }, abstract = {The oral antibiotic therapies administered widely to people and animals can cause gut dysbiosis and barrier disruption inevitably. Increasing attention has been directed toward antibiotic-induced gut dysbiosis, which involves a loss of diversity, changes in the abundances of certain taxa and consequent effects on their metabolic capacity, and the spread of antibiotic-resistant bacterial strains. Treatment with beta-lactam, glycopeptide, and macrolide antibiotics is associated with the depletion of beneficial commensal bacteria in the genera Bifidobacterium and Lactobacillus. The gut microbiota is a reservoir for antibiotic resistance genes, the prevalence of which increases sharply after antibiotic ingestion. The intestinal barrier, which comprises secretory, physical, and immunological barriers, is also a target of antibiotics. Antibiotic induced changes in the gut microbiota composition could induce weakening of the gut barrier through changes in mucin, cytokine, and antimicrobial peptide production by intestinal epithelial cells. Reports have indicated that dietary interventions involving prebiotics, probiotics, omega-3 fatty acids, and butyrate supplementation, as well as fecal microbiota transplantation, can alleviate antibiotic-induced gut dysbiosis and barrier injuries. This review summarizes the characteristics of antibiotic-associated gut dysbiosis and barrier disruption, as well as the strategies for alleviating this condition. This information is intended to provide a foundation for the exploration of safer, more efficient, and affordable strategies to prevent or relieve antibiotic-induced gut injuries.}, }
@article {pmid33198059, year = {2020}, author = {Krishnamoorthy, M and Lenehan, JG and Burton, JP and Maleki Vareki, S}, title = {Immunomodulation in Pancreatic Cancer.}, journal = {Cancers}, volume = {12}, number = {11}, pages = {}, pmid = {33198059}, issn = {2072-6694}, support = {N/A//London Regional Cancer Program's Catalyst Grant Program, Keith Smitt Translational Research Grants./ ; }, abstract = {Pancreatic cancer has a high mortality rate, and its incidence is increasing worldwide. The almost universal poor prognosis of pancreatic cancer is partly due to symptoms presenting only at late stages and limited effective treatments. Recently, immune checkpoint blockade inhibitors have drastically improved patient survival in metastatic and advanced settings in certain cancers. Unfortunately, these therapies are ineffective in pancreatic cancer. However, tumor biopsies from long-term survivors of pancreatic cancer are more likely to be infiltrated by cytotoxic T-cells and certain species of bacteria that activate T-cells. These observations suggest that T-cell activation is essential for anti-tumor immunity in pancreatic cancers. This review discusses the immunological mechanisms responsible for effective anti-tumor immunity and how immune-based strategies can be exploited to develop new pancreatic cancer treatments.}, }
@article {pmid33198044, year = {2020}, author = {Yang, J and Fu, X and Liao, X and Li, Y}, title = {Effects of gut microbial-based treatments on gut microbiota, behavioral symptoms, and gastrointestinal symptoms in children with autism spectrum disorder: A systematic review.}, journal = {Psychiatry research}, volume = {293}, number = {}, pages = {113471}, doi = {10.1016/j.psychres.2020.113471}, pmid = {33198044}, issn = {1872-7123}, mesh = {Anti-Bacterial Agents/administration &amp; dosage ; Autism Spectrum Disorder/epidemiology/psychology/*therapy ; Behavioral Symptoms/epidemiology/psychology/*therapy ; Child ; Child, Preschool ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Diseases/epidemiology/psychology/*therapy ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Male ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; Randomized Controlled Trials as Topic/methods ; Treatment Outcome ; Vitamin A/administration &amp; dosage ; }, abstract = {Many studies have identified some abnormalities in gastrointestinal (GI) physiology (e.g., increased intestinal permeability, overall microbiota alterations, and gut infection) in children with autism spectrum disorder (ASD). Furthermore, changes in the intestinal flora may be related to GI and ASD symptom severity. Thus, we decided to systematically review the effects of gut microbial-based interventions on gut microbiota, behavioral symptoms, and GI symptoms in children with ASD. We reviewed current evidence from the Cochrane Library, EBSCO PsycARTICLES, PubMed, Web of Science, and Scope databases up to July 12, 2020. Experimental studies that used gut microbial-based treatments among children with ASD were included. Independent data extraction and quality assessment of studies were conducted according to the PRISMA statement. Finally, we identified 16 articles and found that some interventions (i.e., prebiotic, probiotic, vitamin A supplementation, antibiotics, and fecal microbiota transplantation) could alter the gut microbiota and improve behavioral symptoms and GI symptoms among ASD patients. Our findings highlight that the gut microbiota could be a novel target for ASD patients in the future. However, we only provided suggestive but not conclusive evidence regarding the efficacy of interventions on GI and behavioral symptoms among ASD patients. Additional rigorous trials are needed to evaluate the effects of gut microbial-based treatments and explore potential mechanisms.}, }
@article {pmid33197883, year = {2020}, author = {Xie, B and Zhang, Y and Qi, H and Yao, H and Shang, Y and Yuan, S and Zhang, J}, title = {Red light exaggerated sepsis-induced learning impairments and anxiety-like behaviors.}, journal = {Aging}, volume = {12}, number = {23}, pages = {23739-23760}, pmid = {33197883}, issn = {1945-4589}, mesh = {Age Factors ; Animals ; Anxiety/*etiology/microbiology/physiopathology/psychology ; *Behavior, Animal ; Disease Models, Animal ; Dysbiosis ; Feces/microbiology ; Gastrointestinal Microbiome ; Intestines/microbiology ; Learning Disabilities/*etiology/microbiology/physiopathology/psychology ; *Light ; Male ; *Maze Learning ; Mice, Inbred C57BL ; Open Field Test ; Sepsis/*complications/microbiology/physiopathology ; Splenomegaly/etiology/physiopathology ; Vagus Nerve/physiopathology ; }, abstract = {Light exerts critical non-visual effects on a multitude of physiological processes and behaviors, including sleep-wake behavior and cognitive function. In this study, we investigated the effects of continued exposure to different colors of light on cognitive function after sepsis in old mice. We found that exposure to red light, but not green light, exaggerated learning impairments and anxiety-like behaviors after sepsis. Red light also induced remarkable splenomegaly and altered the diversity and composition of the fecal microbiota. Pseudo germ-free mice transplanted with fecal bacteria from septic mice exposed to red light developed the same behavioral defects and splenomegaly as their donors. Intriguingly, splenectomy and subdiaphragmatic vagotomy reversed the learning impairments and anxiety-like behaviors resulting from red light exposure after sepsis. After subdiaphragmatic vagotomy, no differences in behavior or spleen size were observed among pseudo germ-free mice transplanted with fecal bacteria from septic mice exposed to different colors of light. Our results suggested that red light exposure after sepsis in old mice causes gut microbiota dysfunction, thus stimulating signaling through the subdiaphragmatic vagus nerve that induces splenomegaly and aggravates learning impairments and anxiety-like behaviors.}, }
@article {pmid33196144, year = {2021}, author = {Timmis, K}, title = {Microbiome transplants to save the planetary surface biosphere.}, journal = {Environmental microbiology reports}, volume = {13}, number = {1}, pages = {50-53}, doi = {10.1111/1758-2229.12906}, pmid = {33196144}, issn = {1758-2229}, mesh = {Adult ; Animals ; Bacteria/classification/genetics/growth &amp; development/isolation &amp; purification ; Behavior ; *Ecosystem ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Planets ; Sheep ; Young Adult ; }, }
@article {pmid33194651, year = {2020}, author = {Chen, YC and Miao, ZF and Yip, KL and Cheng, YA and Liu, CJ and Li, LH and Lin, CY and Wang, JW and Wu, DC and Cheng, TL and Wang, JY}, title = {Gut Fecal Microbiota Transplant in a Mouse Model of Orthotopic Rectal Cancer.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {568012}, pmid = {33194651}, issn = {2234-943X}, abstract = {The gut microbiota is reported to play an important role in carcinogenesis and the treatment of CRC. SW480 and SW620 colon cancer cells integrated with infrared fluorescent proteins were injected into the rectal submucosa of nude mice. In the subsequent 30 days, we observed tumor growth weekly using an in vivo imaging system. The bacterial solution was infused anally into the mice to perform bacterial transplant. Phosphate-buffered saline, Acinetobacter lwoffii, and Bifidobacterium longum solutions were infused individually. The 16S ribosomal DNA (rDNA) and polymerase chain reaction of murine feces were investigated to confirm the colonization of target bacteria. In the SW620 orthotopic xenograft rectal cancer model, 4 of 5 mice developed rectal cancer by 30 days after submucosal injection. In the SW480 orthotopic xenograft rectal cancer model, 2 of 6 mice developed rectal cancer by 30 days after submucosal injection. For the 16S rDNA analysis, the mice receiving the bacterial solution infusion demonstrated positive findings for A. lwoffii and B. longum. With the successful establishment of a mouse model of orthotopic rectal cancer and transplant of target bacteria, we can further explore the relationship between gut microbiota and CRC. The role of fecal microbiota transplant in the treatment and alleviation of adverse events of chemotherapy in CRC could be clarified in subsequent studies.}, }
@article {pmid33193813, year = {2020}, author = {Tian, Y and Zuo, L and Guo, Q and Li, J and Hu, Z and Zhao, K and Li, C and Li, X and Zhou, J and Zhou, Y and Li, XA}, title = {Potential role of fecal microbiota in patients with constipation.}, journal = {Therapeutic advances in gastroenterology}, volume = {13}, number = {}, pages = {1756284820968423}, pmid = {33193813}, issn = {1756-283X}, abstract = {BACKGROUND: We evaluated the safety and efficacy of fecal microbiota transplantation (FMT) for chronic functional constipation (CFC) ineffectively treated by conventional constipation medication.<br><br>METHODS: Thirty-four patients with CFC underwent FMT treatment (three rounds, via gastroscopy). Clinical scales, including the Wexner constipation score as the main index of efficiency, were completed at baseline; after each treatment, and at 2 and 3&#x2009;months of follow up. Secondary evaluation indices included the self-assessment of constipation symptoms, patient assessment constipation quality-of-life questionnaire, Bristol stool form scale, and Zung's self-rating depression and anxiety scales. Gastrointestinal motility, motilin, gastrin, nitric oxide (NO), and 5-hydroxytryptamine (5-HT) were assessed before and after treatment. Intestinal flora changes were assessed by 16S ribosomal ribonucleic acid (rRNA) sequencing.<br><br>RESULTS: There were no serious adverse reactions. The clinical cure rate was 73.5% (25/34), clinical remission rate was 14.7% (5/34), and the inefficiency rate was 11.8% (4/34). Clinical scale data indicated that the FMT treatment was effective. Furthermore, FMT treatment promoted intestinal peristalsis, increased gastrointestinal motility, and increased serum NO and 5-HT levels. The 16S rRNA sequencing data indicated that high abundances of Bacteroides, Klebsiella, Megamonas, Erysipelotrichaceae and Epulopiscium may be the cause of constipation, and high abundances of Prevotella, Acidaminococcus and Butyricimonas may be the main factors in curing constipation.<br><br>CONCLUSION: Treatment with FMT regulates the intestinal microflora and changes the abundance of CFC-associated bacterial flora to improve constipation.}, }
@article {pmid33193357, year = {2020}, author = {Marietta, E and Mangalam, AK and Taneja, V and Murray, JA}, title = {Intestinal Dysbiosis in, and Enteral Bacterial Therapies for, Systemic Autoimmune Diseases.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {573079}, pmid = {33193357}, issn = {1664-3224}, support = {P30 ES005605/ES/NIEHS NIH HHS/United States ; R01 AI075262/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Autoimmune Diseases/immunology/microbiology/*therapy ; *Autoimmunity ; Bacteria/*growth &amp; development/immunology ; Clinical Trials as Topic ; Disease Models, Animal ; Dysbiosis ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; Host-Pathogen Interactions ; Humans ; Intestines/immunology/*microbiology ; Probiotics/*therapeutic use ; Treatment Outcome ; }, abstract = {Recent studies have shown that a number of common autoimmune diseases have perturbations of their intestinal microbiome (dysbiosis). These include: Celiac Disease (CeD), Multiple Sclerosis (MS), Rheumatoid Arthritis (RA), Sjogren's Syndrome (SS), and Type 1 diabetes (T1D). All of these have intestinal microbiomes that are different from healthy controls. There have been numerous studies using animal models of single probiotics (monoclonal) or mixtures of probiotics (polyclonal) and even complete microbiota transfer (fecal microbial transfer-FMT) to inhibit or delay the onset of autoimmune diseases such as the aforementioned common ones. However, proportionally, fewer clinical trials have utilized monoclonal therapies or FMT than polyclonal therapies for treating autoimmune diseases, even though bacterial mono-therapies do inhibit the development of autoimmune diseases and/or delay the onset of autoimmune diseases in rodent models of those autoimmune diseases. In this review then, we review the previously completed and currently ongoing clinical trials that are testing bacterial therapies (FMT, monoclonal, and polyclonal) to treat common autoimmune dseases and discuss the successes in using bacterial monotherapies to treat rodent models of these common autoimmune diseases.}, }
@article {pmid33193352, year = {2020}, author = {Schmidt, CJ and Wenndorf, K and Ebbers, M and Volzke, J and Müller, M and Strübing, J and Kriebel, K and Kneitz, S and Kreikemeyer, B and Müller-Hilke, B}, title = {Infection With Clostridioides difficile Attenuated Collagen-Induced Arthritis in Mice and Involved Mesenteric Treg and Th2 Polarization.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {571049}, pmid = {33193352}, issn = {1664-3224}, mesh = {Animals ; Arthritis, Experimental/*immunology ; Arthritis, Rheumatoid/*immunology ; Cell Differentiation ; Clostridioides difficile/*physiology ; Clostridium Infections/*immunology ; Disease Models, Animal ; Disease Resistance ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Lymphocyte Activation ; Mesentery/*immunology ; Mice ; Mice, Inbred DBA ; T-Lymphocytes, Regulatory/*immunology ; Th2 Cells/*immunology ; }, abstract = {OBJECTIVES: Rheumatoid arthritis is an autoimmune disease with multifactorial etiopathogenesis. Among the environmental factors, mucosal infections and the inducing pathobionts are gaining increasing attention. We here set out to explore the gut-joint-axis and the impact of Clostridioides difficile infection on subsequent arthritis.<br><br>METHODS: We combined C. difficile infection in DBA/1J &#xd7; B10.Q F1 mice with collagen induced arthritis (CIA). Mice were infected via oral gavage and infection was monitored by weight loss, colonic histology, and antibodies against bacteria. Scoring of arthritis was performed macroscopically. Intestinal microbiomes were analyzed and immune responses were monitored via quantification of transcription factor-specific mRNA isolated from the inguinal and mesenteric lymph nodes.<br><br>RESULTS: Infection with C. difficile VPI 10463 resulted in significant weight loss and severe colitis yet accelerated the reversal towards the original microbiome after antibiotic treatment. Spontaneous clearance of VPI 10463 infection reduced the incidence of subsequent CIA and led to mesenteric Treg and Th2 polarization. However, this attenuating effect was abrogated if VPI 10463 was eradicated via vancomycin followed by fecal microbiota transplantation. Moreover, VPI 10463 infection following the onset of CIA lacked therapeutic potential.<br><br>CONCLUSION: Our results demonstrate that infection with C. difficile VPI10463 induced an inflammation of the gut that protected from subsequent arthritis development in mice. Both, microbial changes to the gut and immune cell mobilization and/or polarization may have contributed to arthritis protection. The prospect of potential therapeutic benefits resulting from C. difficile infections or some byproduct thereof call for further experiments that help elucidate exact mechanisms.}, }
@article {pmid33193273, year = {2020}, author = {Geng, ST and Zhang, ZY and Wang, YX and Lu, D and Yu, J and Zhang, JB and Kuang, YQ and Wang, KH}, title = {Regulation of Gut Microbiota on Immune Reconstitution in Patients With Acquired Immunodeficiency Syndrome.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {594820}, pmid = {33193273}, issn = {1664-302X}, abstract = {Human immunodeficiency virus type 1 (HIV-1) infection of CD4[+] T cells in the gut plays an insidious role in acquired immunodeficiency syndrome (AIDS) pathogenesis. Host immune function is closely related to gut microbiota. Changes in the gut microbiota cause a different immune response. Previous studies revealed that HIV-1 infection caused changes in gut microbiota, which induced immune deficiency. HIV-1 infection results in an abnormal composition and function of the gut microbiota, which may disrupt the intestinal epithelial barrier and microbial translocation, leading to long-term immune activation, including inflammation and metabolic disorders. At the same time, an abnormal gut microbiota also hinders the effect of antiviral therapy and affects the immune reconstruction of patients. However, studies on the impact of the gut microbiota on immune reconstitution in patients with HIV/AIDS are still limited. In this review, we focus on changes in the gut microbiota caused by HIV infection, as well as the impact and regulation of the gut microbiota on immune function and immune reconstitution, while we also discuss the potential impact of probiotics/prebiotics and fecal microbiota transplantation (FMT) on immune reconstitution.}, }
@article {pmid33191778, year = {2020}, author = {Souza, ELS and Campos, CLV and Reis, DC and Cassali, GD and Generoso, SV and Cardoso, VN and Azevedo, V and Medeiros, JD and Fernandes, GR and Nicoli, JR and Martins, FS}, title = {Beneficial effects resulting from oral administration of Escherichia coli Nissle 1917 on a chronic colitis model.}, journal = {Beneficial microbes}, volume = {11}, number = {8}, pages = {779-790}, doi = {10.3920/BM2020.0045}, pmid = {33191778}, issn = {1876-2891}, mesh = {Animals ; Colitis, Ulcerative/*prevention &amp; control ; Colon/pathology ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Escherichia coli/classification/*physiology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/physiology ; Germ-Free Life ; Immunoglobulin A/analysis ; Interferon-gamma/blood ; Interleukin-13/blood ; Interleukin-5/blood ; Intestinal Mucosa/*microbiology/pathology ; Mice ; Probiotics/*pharmacology ; RNA, Ribosomal, 16S/genetics ; Tumor Necrosis Factor-alpha/blood ; }, abstract = {Inflammatory bowel diseases (IBD) are chronic processes involving a deregulated immune response against intestinal microbiota in genetically susceptible individuals. Ulcerative colitis (UC) is an IBD restricted to colonic mucosa and its chronicity is a predisposing factor for colorectal cancer (CRC). Probiotics have been investigated as an adjuvant treatment for UC, and Escherichia coli Nissle 1917 (EcN) was the focus of our investigation. The aim of this study was to investigate the preventive effect of the EcN probiotic in an experimental model of chronic colitis in germ-free (GF) and conventional (CV) mice. CV female mice were used for clinical, immunological and permeability experiments. GF mice were used for a faecal microbiota transplantation assay. To induce colitis, three cycles of 3.0% dextran sulphate sodium (DSS) were administered to the animals. For probiotic treatment, the mice received a daily intragastric gavage of 9.0 log10 cfu of EcN, beginning 10 days before colitis induction and continuing until the end of the experiment. EcN presented beneficial effects when administered preventively. Daily Disease Activity Index (DAI) evolution demonstrated significant difference in remission periods after the first two DSS cycles and during the third one. Reduction in bacterial translocation after probiotic treatment indicated protection of the intestinal barrier. Associated with mucosal preservation, restoration of secretory immunoglobulin A levels and reduction of interleukin (IL)-5, IL-13, tumour necrosis factor and interferon-γ levels were observed in EcN treatment. Finally, when microbiota modification was verified, 16S rRNA-based compositional analysis showed variation of intestinal microbiota between the control and colitis groups. After faecal transplantation using GF mice, it was observed that EcN treatment in CV mice might result in modulated intestinal microbiota. This was observed indirectly in the reduced daily DAI, when colitis was compared with treated group. In conclusion, EcN presented beneficial effects in this model, suggesting its usefulness for treating UC.}, }
@article {pmid33190214, year = {2021}, author = {Zhou, Y and Ni, X and Duan, L and Niu, L and Liu, Q and Zeng, Y and Wang, Q and Wang, J and Khalique, A and Pan, K and Jing, B and Zeng, D}, title = {Lactobacillus plantarum BSGP201683 Improves the Intestinal Barrier of Giant Panda Microbiota-Associated Mouse Infected by Enterotoxigenic Escherichia coli K88.}, journal = {Probiotics and antimicrobial proteins}, volume = {13}, number = {3}, pages = {664-676}, pmid = {33190214}, issn = {1867-1314}, mesh = {Animals ; *Enterotoxigenic Escherichia coli ; Escherichia coli Infections/*veterinary ; *Gastrointestinal Microbiome ; Intestines/*microbiology ; *Lactobacillus plantarum ; Mice ; Occludin ; *Ursidae/microbiology ; }, abstract = {Giant pandas often suffered from gastrointestinal disease, especially the captive sub-adult one. Our study aims to investigate whether L. plantarum G83, a good panda-derived probiotic, can improve the intestinal barrier against the enterotoxigenic Escherichia coli K88 (E. coli K88) infection in giant panda microbiota-associated mice (GPAM). We treated SPF mice with antibiotics cocktail and transplanted the giant panda intestinal microbiota to set up a GPAM. Our results demonstrated that the microbiota of GPAM changed over time and was relatively stable in the short-term experiment (2-4 weeks). Whereafter, the GPAM pretreated with L. plantarum G83 for 15 days and infected with enterotoxigenic E. coli K88. The result indicated that the number of Bifidobacteria spp. increased in GPAM-G and GPAM-GE groups; the Lactobacillus spp. only increased in the GPAM-G group. Although the abundance of Enterobacteriaceae spp. only decreased in the GPAM-G group, the copy number of Escherichia coli in the GPAM-E group was significantly lower than that in the other groups. Meanwhile, the L. plantarum G83-induced alteration of microbiota could increase the mRNA expression of Claudin-1, Zo-1, and Occludin-1 in the GPAM-G group in the ileum; only Occludin-1 was increased in the GPAM-GE group. The sIgA in the ileum showed a positive response, also the result of body weight and histology in both the GPAM-G and GPAM-GE group. These results indicated that the L. plantarum G83 could improve the intestinal barrier to defense the enterotoxigenic E. coli K88 invasion.}, }
@article {pmid33188418, year = {2021}, author = {Giovanni, MY and Schneider, JS and Calder, T and Fauci, AS}, title = {Refocusing Human Microbiota Research in Infectious and Immune-mediated Diseases: Advancing to the Next Stage.}, journal = {The Journal of infectious diseases}, volume = {224}, number = {1}, pages = {5-8}, pmid = {33188418}, issn = {1537-6613}, mesh = {Asthma/etiology ; Communicable Diseases/*etiology/microbiology ; Disease Susceptibility ; Fecal Microbiota Transplantation ; Humans ; Hypersensitivity/etiology ; Immune System/physiology ; Immune System Diseases/*etiology/microbiology ; Microbiota/*physiology ; }, abstract = {Changes in the microbiota are associated with disease susceptibility, immune system development, and responses to treatment. Refocusing research to elucidate the causal links between the human microbiota and infectious and immune-mediated diseases will be critical to harnessing its power to prevent, diagnose, and treat such diseases.}, }
@article {pmid33188046, year = {2020}, author = {}, title = {On the threshold of a revolution….}, journal = {The Veterinary record}, volume = {187}, number = {Suppl 1}, pages = {6-7}, doi = {10.1136/vr.m4368}, pmid = {33188046}, issn = {2042-7670}, mesh = {Animals ; Cats ; Dogs ; Fecal Microbiota Transplantation/*veterinary ; Feces/microbiology ; Forecasting ; *Gastrointestinal Microbiome ; Humans ; United Kingdom ; Veterinary Medicine/organization &amp; administration/*trends ; }, abstract = {A deeper understanding of the microbiome could help inform individualised treatment for animals and, in the use of faecal microbiota transplantation, a practical application of such knowledge already exists.}, }
@article {pmid33187097, year = {2020}, author = {Nourrisson, C and Brunet, J and Flori, P and Moniot, M and Bonnin, V and Delbac, F and Poirier, P}, title = {Comparison of DNA Extraction Methods and Real-Time PCR Assays for the Detection of Blastocystis sp. in Stool Specimens.}, journal = {Microorganisms}, volume = {8}, number = {11}, pages = {}, pmid = {33187097}, issn = {2076-2607}, abstract = {Diagnosis of Blastocystis in stool may be challenging, as microscopic examination and culture-based methods have demonstrated low sensitivity. Molecular detection assays are now available for this enteric parasite, based on "in-house" or commercial-developed techniques. The aim of this study was to assess and compare the performance of (i) two DNA extraction methods (manual versus automated), and (ii) four qPCR assays (three "in-house" and one commercialized), for detection of Blastocystis sp. in human stools. One hundred and forty stools were included, among which 76 were confirmed to be positive for Blastocystis. The manual DNA extraction method allowed for the identification of significantly more positive specimens than the automated method (p < 0.05). In particular, specimens with a low parasite load were negative when DNA was extracted with the automated process. The four qPCR assays also had variable performances, with the commercialized assay being the most sensitive (84%) but the least specific (82%). Overall, for all qPCR assays, the specificity decreased when the sensitivity increased. Blastocystis' subtype, notably the subtype 4, influenced these performances. Our results indicate that the positivity rate for the detection of Blastocystis in stools could be variable according to the DNA extraction method and the qPCR assay used. These pitfalls need to be considered for the selection of method and interpretation of results, particularly considering the search of this intestinal parasite in a donor before fecal microbiota transplantation.}, }
@article {pmid33186366, year = {2020}, author = {Ramírez, GA and Richardson, E and Clark, J and Keshri, J and Drechsler, Y and Berrang, ME and Meinersmann, RJ and Cox, NA and Oakley, BB}, title = {Broiler chickens and early life programming: Microbiome transplant-induced cecal community dynamics and phenotypic effects.}, journal = {PloS one}, volume = {15}, number = {11}, pages = {e0242108}, pmid = {33186366}, issn = {1932-6203}, mesh = {Animals ; Cecum/microbiology ; Chickens/growth &amp; development/*microbiology ; Fecal Microbiota Transplantation/methods/*veterinary ; *Gastrointestinal Microbiome ; *Phenotype ; }, abstract = {The concept of successional trajectories describes how small differences in initial community composition can magnify through time and lead to significant differences in mature communities. For many animals, the types and sources of early-life exposures to microbes have been shown to have significant and long-lasting effects on the community structure and/or function of the microbiome. In modern commercial poultry production, chicks are reared as a single age cohort and do not directly encounter adult birds. This scenario is likely to initiate a trajectory of microbial community development that is significantly different than non-industrial settings where chicks are exposed to a much broader range of environmental and fecal inocula; however, the comparative effects of these two scenarios on microbiome development and function remain largely unknown. In this work, we performed serial transfers of cecal material through multiple generations of birds to first determine if serial transfers exploiting the ceca in vivo, rather than the external environment or artificial incubations, can produce a stable microbial community. Subsequently, we compared microbiome development between chicks receiving this passaged, i.e. host-selected, cecal material orally, versus an environmental inoculum, to test the hypothesis that the first exposure of newly hatched chicks to microbes determines early GI microbiome structure and may have longer-lasting effects on bird health and development. Cecal microbiome dynamics and bird weights were tracked for a two-week period, with half of the birds in each treatment group exposed to a pathogen challenge at 7 days of age. We report that: i) a relatively stable community was derived after a single passage of transplanted cecal material, ii) this cecal inoculum significantly but ephemerally altered community structure relative to the environmental inoculum and PBS controls, and iii) either microbiome transplant administered at day-of-hatch appeared to have some protective effects against pathogen challenge relative to uninoculated controls. Differentially abundant taxa identified across treatment types may inform future studies aimed at identifying strains associated with beneficial phenotypes.}, }
@article {pmid33185695, year = {2021}, author = {Jaber, A and Hemmer, S and Klotz, R and Ferbert, T and Hensel, C and Eisner, C and Ryang, YM and Obid, P and Friedrich, K and Pepke, W and Akbar, M}, title = {Bowel dysfunction after elective spinal surgery: etiology, diagnostics and management based on the medical literature and experience in a university hospital.}, journal = {Der Orthopade}, volume = {50}, number = {6}, pages = {425-434}, pmid = {33185695}, issn = {1433-0431}, mesh = {*Analgesics, Opioid ; Constipation ; Elective Surgical Procedures ; Hospitals ; Humans ; *Spinal Cord Injuries ; }, abstract = {BACKGROUND: Bowel dysfunction after spinal surgery is often underestimated and if not treated in a timely manner can lead to undesirable surgical interventions or fatal complications. The current medical literature primarily focuses on bowel dysfunction as a result of spinal injury.<br><br>OBJECTIVE: The purpose of this review is to explore this topic in evaluating current evidence regarding the causes of acute bowel dysfunction after elective spinal surgery, primarily the thoracolumbar spine. Since available evidence for recommendations of treatment is scarce, an interdisciplinary management approach for treatment of bowel dysfunction following spinal surgery is also formulated.<br><br>MATERIAL AND METHODS: An extensive literature search was carried out on PubMed. Keywords that were used in the search included bowel dysfunction, obstruction, postoperative ileus, spinal surgery, spinal fusion, constipation, opioid-induced constipation, colonic pseudo-obstruction, ischemic colitis, immobility-induced bowel changes, epidural anesthesia and diet. Relevant studies were chosen and included in the review. The treatment approach used in the spine center of a&#xa0;university hospital was included.<br><br>RESULTS: Current research mainly focuses on investigating the nature and symptomatology of chronic bowel dysfunction after spinal cord injury. Emphasis on the acute phase of bowel dysfunction in patients after elective spinal surgery is lacking. The comorbidities that exacerbate bowel dysfunction postoperatively are well-defined. There has been refinement and expansion of the pharmacological and nonpharmacological treatment that could be implemented. Enough evidence exists to provide sufficient care.<br><br>CONCLUSION: Management of acute bowel dysfunction after spinal surgery requires a&#xa0;comprehensive and individualized approach, encompassing comorbidities, behavioral changes, medications and surgery. Close supervision and timely treatment could minimize further complications. Research is required to identify patients who are at a&#xa0;higher risk of developing bowel dysfunction after specific spinal procedures.}, }
@article {pmid33180654, year = {2020}, author = {Badran, M and Mashaqi, S and Gozal, D}, title = {The gut microbiome as a target for adjuvant therapy in obstructive sleep apnea.}, journal = {Expert opinion on therapeutic targets}, volume = {24}, number = {12}, pages = {1263-1282}, pmid = {33180654}, issn = {1744-7631}, support = {R56 HL140548/HL/NHLBI NIH HHS/United States ; RF1 AG061824/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Dysbiosis/*complications/therapy ; Fatty Acids, Volatile/administration &amp; dosage ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; Sleep Apnea, Obstructive/etiology/*therapy ; }, abstract = {Introduction: Gut dysbiosis is assumed to play a role in obstructive sleep apnea (OSA)-associated morbidities. Pre- and probiotics, short chain fatty acids (SCFA) and fecal matter transplantation (FMT) may offer potential as novel therapeutic strategies that target this gut dysbiosis. As more mechanisms of OSA-induced dysbiosis are being elucidated, these novel approaches are being tested in preclinical and clinical development. Areas covered: We examined the evidence linking OSA to gut dysbiosis and discuss the effects of pre- and probiotics on associated cardiometabolic, neurobehavioral and gastrointestinal disorders. The therapeutic potential of SCFA and FMT are also discussed. We reviewed the National Center for Biotechnology Information database, including PubMed and PubMed Central between 2000 - 2020. Expert opinion: To date, there are no clinical trials and only limited evidence from animal studies describing the beneficial effects of pre- and probiotic supplementation on OSA-mediated dysbiosis. Thus, more work is necessary to assess whether prebiotics, probiotics and SCFA are promising future novel strategies for targeting OSA-mediated dysbiosis.}, }
@article {pmid33177380, year = {2021}, author = {Tamilarasan, AG and Krishnananthan, T}, title = {Faecal microbiota transplantation: what's beyond Clostridium difficile infection?.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {33}, number = {4}, pages = {487-494}, doi = {10.1097/MEG.0000000000001938}, pmid = {33177380}, issn = {1473-5687}, mesh = {*Clostridium Infections/therapy ; *Colitis, Ulcerative/therapy ; Dysbiosis/therapy ; *Enterocolitis, Pseudomembranous/therapy ; Fecal Microbiota Transplantation ; Feces ; Humans ; }, abstract = {Over the last decade, major advancements have been made in our understanding of both the beneficial and detrimental role that microorganisms play in our innate functioning. Research into the intestinal microbiota has moved from the laboratory into our medical clinics and is being put forth as an effective therapy for a range of medical conditions, not only limited to the gastrointestinal system. The clearest example of this progression has been in the treatment of Clostridium difficile infection; however, faecal microbiota transplantation has also been shown to have a positive effect in the treatment of inflammatory disorders, such as ulcerative colitis. In this review article, we will appraise the existing literature examining the role the intestinal microbiota plays in the pathogenesis of disease and the therapeutic utility of faecal microbiota transplantation in restoring homeostasis. In many cases, these studies are in a preclinical setting, are small in scale and often are not placebo-controlled; however, the results from these studies report interesting associations between intestinal dysbiosis and disease development, as well as the beneficial effects of faecal microbiota transplantation in reversing this process.}, }
@article {pmid33176177, year = {2021}, author = {Zhang, Y and Xie, B and Chen, X and Zhang, J and Yuan, S}, title = {A key role of gut microbiota-vagus nerve/spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration.}, journal = {Life sciences}, volume = {265}, number = {}, pages = {118736}, doi = {10.1016/j.lfs.2020.118736}, pmid = {33176177}, issn = {1879-0631}, mesh = {Animals ; Cytokines ; Gastrointestinal Microbiome/drug effects/*physiology ; Inflammation ; Interleukin-10 ; Interleukin-6 ; Lipopolysaccharides/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Sepsis ; Sleep Deprivation/metabolism/*physiopathology ; Spleen/drug effects/*metabolism/physiology ; Tumor Necrosis Factor-alpha ; Vagus Nerve/drug effects/metabolism/*physiology ; }, abstract = {AIMS: Sleep deprivation (SD) correlates with exacerbated systemic inflammation after sepsis. However, the underlying mechanisms remain unclear. This study aimed to evaluate the roles and mechanisms of SD in inflammatory organ injury after lipopolysaccharide (LPS) administration.<br><br>MAIN METHODS: Mice were intraperitoneally injected with LPS followed by 3 consecutive days of SD. The pseudo germ-free (PGF) mice received fecal microbiota transplant by being gavaged with supernatant from fecal suspension of septic mice with or without SD. The subdiaphragmatic vagotomy (SDV) or splenectomy was performed 14&#xa0;days prior to LPS injection or antibiotics administration.<br><br>KEY FINDINGS: Post-septic SD increased the plasma levels of interleukin (IL)-6 and tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), reduced IL-10 plasma level, increased spleen weight, and promoted inflammatory injury of the lung, liver and kidney. The relative abundance of Proteobacteria and its subgroups were increased after post-septic SD. PGF mice transplanted with fecal bacteria from septic mice subjected to SD developed splenomegaly, systemic inflammation, organ inflammation and damage as their donors did. Intriguingly, SDV abolished the aggravated effects of SD on splenomegaly and inflammatory organ injury in septic mice received SD or in PGF mice transplanted with fecal bacteria from septic mice subjected to SD. Furthermore, splenectomy also abrogated the increase in IL-6 and TNF-&#x3b1; plasma levels and the decrease in IL-10 plasma level in PGF mice transplanted with fecal bacteria from septic mice subjected to SD.<br><br>SIGNIFICANCE: Gut microbiota-vagus nerve axis and gut microbiota-spleen axis play key roles in modulating systemic inflammation induced by SD after LPS administration.}, }
@article {pmid33175698, year = {2020}, author = {Ademe, M}, title = {Benefits of fecal microbiota transplantation: A comprehensive review.}, journal = {Journal of infection in developing countries}, volume = {14}, number = {10}, pages = {1074-1080}, doi = {10.3855/jidc.12780}, pmid = {33175698}, issn = {1972-2680}, mesh = {Animals ; Dysbiosis/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Mice ; }, abstract = {A growing body of literatures showed the interaction of dysbiotic gut with a wide range of disorders, and the clinical use of fecal microbiota transplantation (FMT) shifted from infectious disease to non-communicable disorders. Despite the promising therapeutic benefits of FMT, the exact mechanisms through which fecal recipients benefit from the fecal intervention are not well understood. However, owing to the advantages of having a healthy gut microbiome, possible mechanisms of actions of FMT has been described. On the one hand, through direct ecological competition, FMT may potentially stimulate decolonization of pathogenic microorganisms and increase host resistance to pathogens. Moreover, following dysbiosis, abnormal microbial colonization of the gastrointestinal tract may also cause excessive or dysregulated immune response, resulting in chronic inflam-mation and the development of mucosal lesions. In this regard, repopulating gut microbiome through FMT helps to restore immune function and reduce host damage. On the other hand, FMT helps to restore essential metabolites used for host metabolism, including short-chain fatty acids (SCFA), antimicrobial peptides (AMP), bacteriocins and bile acids. Therefore, in this review, the existing evidences regarding the mechanisms of action, current opportunities and challenges of FMT will be described.}, }
@article {pmid33172329, year = {2021}, author = {Kim, S and Lee, JY and Shin, SG and Kim, JK and Silwal, P and Kim, YJ and Shin, NR and Kim, PS and Won, M and Lee, SH and Kim, SY and Sasai, M and Yamamoto, M and Kim, JM and Bae, JW and Jo, EK}, title = {ESRRA (estrogen related receptor alpha) is a critical regulator of intestinal homeostasis through activation of autophagic flux via gut microbiota.}, journal = {Autophagy}, volume = {17}, number = {10}, pages = {2856-2875}, pmid = {33172329}, issn = {1554-8635}, mesh = {Animals ; *Autophagy/physiology ; Dextran Sulfate/metabolism/pharmacology ; Estrogens/metabolism ; *Gastrointestinal Microbiome ; Homeostasis ; Humans ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism ; }, abstract = {The orphan nuclear receptor ESRRA (estrogen related receptor alpha) is critical in mitochondrial biogenesis and macroautophagy/autophagy function; however, the roles of ESRRA in intestinal function remain uncharacterized. Herein we identified that ESRRA acts as a key regulator of intestinal homeostasis by amelioration of colonic inflammation through activation of autophagic flux and control of host gut microbiota. Esrra-deficient mice presented with increased susceptibility to dextran sodium sulfate (DSS)-induced colitis with upregulation of intestinal inflammation. In addition, esrra-null mice had depressed AMP-activated protein kinase phosphorylation (AMPK), lower levels of TFEB (transcription factor EB), and accumulation of SQSTM1/p62 (sequestosome 1) with defective mitochondria in intestinal tissues. Esrra-deficient mice showed distinct gut microbiota composition and significantly higher microbial diversity than wild-type (WT) mice. Cohousing or fecal microbiota transplantation from WT mice to Esrra-deficient mice ameliorated DSS-induced colitis severity. Importantly, patients with ulcerative colitis (UC) had significantly decreased ESRRA expression in intestinal mucosal tissues that correlated with disease activity, suggesting clinical relevance of ESRRA in UC. Taken together, our results show that ESRRA contributes to intestinal homeostasis through autophagy activation and gut microbiota control to protect the host from detrimental inflammation and dysfunctional mitochondria.Abbreviations: ABX, antibotics; AMPK, AMP-activated protein kinase; ATP5A1, ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1; BECN1, beclin1, autophagy related, CCL, C-C motif chemokine ligand; CD, Crohn disease; CLDN, claudin; COX4I1, cytochrome c oxidase subunit 4I1; cKO, conditional knockout; cWT, conditional wild-type; CXCL, C-X-C motif chemokine ligand; DAI, disease activity index; DSS, dextran sodium sulfate; EGFP, enhanced green fluorescent protein; ESRR, estrogen related receptor; ESRRA, estrogen related receptor alpha; Esrra+/+, Esrra wild type; esrra-/-, esrra homozygous knockout; FMT, fecal microbiota transplantation; GABARAP, gamma-aminobutyric acid receptor associated protein; GSEA, gene set enrichment analysis; IBD, inflammatory bowel disease; IL, interleukin; KO, knockout; LAMP1, lysosomal-associated membrane protein 1; LCN2, lipocalin 2; LEfSe, linear discriminant analysis (LDA) effect size; LPS, lipopolysachharide; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; NDUFAB1, NADH: ubiquinone oxidoreductase subunit AB1; OCLN, occludin; OUT, operational taxonomic unit; OXPHOS, oxidative phosphorylation; PCoA, principal coordinate analysis; PPARGC1A, PPARG coactiva- tor 1 alpha; PRKAA, 5'-AMP-activated protein kinase catalytic subunit alpha; PTGS2/COX2, prostaglandin-endoperoxide synthase 2; RAB7, member RAS oncogene family; SDHB, succinate dehydrogenase complex, subunit B, iron sulfur (Ip); SQSTM1/p62, sequestosome 1; S100A9, S100 calcium binding protein A9 (calgranulin B); TCA, tricarboxylic acid; TFEB, transcription factor EB; TNF, tumor necrosis factor; UC, ulcerative colitis; UCP2, uncoupling protein 2 (mitochondrial, proton carrier); UQCRC1, ubiquinol-cytochrome c reductase core protein 1; UVRAG, UV radiation resistance associated gene; Vil1, villin; VPS11, VPS11, CORVET/HOPS core sub-unit; WT, wild type.}, }
@article {pmid33169470, year = {2021}, author = {Balaphas, A and Schiltz, B and Liot, E and Robert-Yap, J and Ris, F}, title = {What is the role of stem cell therapy in the treatment of anal incontinence?.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {23}, number = {2}, pages = {551-552}, doi = {10.1111/codi.15433}, pmid = {33169470}, issn = {1463-1318}, mesh = {Anal Canal/surgery ; *Fecal Incontinence/therapy ; Humans ; Stem Cell Transplantation ; }, }
@article {pmid33168782, year = {2020}, author = {Yang, Z and Xia, Q and Lu, D and Yue, H and Zhang, J and Li, Y and Zhang, B and Li, X and Cao, M}, title = {Human mesenchymal stem cells treatment improved hepatic lesions and reversed gut microbiome disorder in non-alcoholic steatohepatitis.}, journal = {Aging}, volume = {12}, number = {21}, pages = {21660-21673}, pmid = {33168782}, issn = {1945-4589}, mesh = {Animals ; Bacteria/*metabolism ; Cells, Cultured ; Cellular Microenvironment ; Disease Models, Animal ; Dysbiosis ; Feces/microbiology ; Fibrosis/metabolism/microbiology/pathology/*surgery ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Intestines/*microbiology ; Liver/*metabolism/pathology ; Male ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*metabolism ; Metabolome ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/metabolism/microbiology/pathology/*surgery ; Phenotype ; Umbilical Cord/cytology ; }, abstract = {Effective therapies for non-alcoholic steatohepatitis (NASH) are urgently needed. We investigated the effect of human mesenchymal stem cells (hMSCs) on the intestinal flora in NASH treatment. We isolated the hMSCs from the umbilical cords and divided male C57BL/6 mice into three groups, namely, chow, methionine-choline-deficient (MCD), and MCD+hMSCs. After collecting the feces and liver of the mice, we evaluated the histological changes in the liver and measured the inflammatory and fibrogenesis cytokines. Fecal microbiome and metabolome were analyzed using 16S rRNA gene sequencing analyses. The hMSCs treatment could alleviate hepatic steatosis, inflammation and fibrosis induced by MCD diet. It could also reverse the microbiome and metabolome disorders in the NASH model. Correlation analysis of the interaction among bacteria amplified the effects of the bacteria in host. In conclusion, hMSCs treatment could improve NASH-related lesions and reverse gut microbiome and metabolome disorder in NASH.}, }
@article {pmid33167783, year = {2020}, author = {Benech, N and Sokol, H}, title = {Expert centres for faecal microbiota transplantation: The guarantee for safe and effective use of faecal transplants.}, journal = {United European gastroenterology journal}, volume = {8}, number = {10}, pages = {1145-1146}, pmid = {33167783}, issn = {2050-6414}, mesh = {*Blastocystis ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid33166939, year = {2021}, author = {Singh, R and Zogg, H and Wei, L and Bartlett, A and Ghoshal, UC and Rajender, S and Ro, S}, title = {Gut Microbial Dysbiosis in the Pathogenesis of Gastrointestinal Dysmotility and Metabolic Disorders.}, journal = {Journal of neurogastroenterology and motility}, volume = {27}, number = {1}, pages = {19-34}, pmid = {33166939}, issn = {2093-0879}, abstract = {Of all microorganisms in the human body, the largest and most complex population resides in the gastrointestinal (GI) tract. The gut microbiota continuously adapts to the host environment and serves multiple critical functions for their hosts, including regulating host immunity, procuring energy from food, and preventing the colonization of pathogens. Mounting evidence has suggested gut microbial imbalance (dysbiosis) as a core pathophysiology in the development of GI motility and metabolic disorders, such as irritable bowel syndrome and diabetes. Current research has focused on discovering associations between these disorders and gut microbial dysbiosis; however, whether these associations are a consequence or cause is still mostly unexplored. State-of-the-art studies have investigated how gut microbes communicate with our body systems through microbiota-derived metabolites and how they are able to modulate host physiology. There is now mounting evidence that alterations in the composition of small intestinal microbes have an association with GI dysmotility and metabolic disorders. Although treatment options for gut microbial dysbiosis are currently limited, antibiotics, fecal microbiota transplantation, probiotics, and dietary interventions are currently the best options. However, treatment with broad-spectrum antibiotics has been viewed with skepticism due to the risk of developing antibiotic resistant bacteria. Studies are warranted to elucidate the cellular and molecular pathways underlying gut microbiota-host crosstalk and for the development of a powerful platform for future therapeutic approaches. Here, we review recent literature on gut microbial alterations and/or interactions involved in the pathophysiology of GI dysmotility and metabolic disorders.}, }
@article {pmid33166735, year = {2021}, author = {Koszewicz, M and Jaroch, J and Brzecka, A and Ejma, M and Budrewicz, S and Mikhaleva, LM and Muresanu, C and Schield, P and Somasundaram, SG and Kirkland, CE and Avila-Rodriguez, M and Aliev, G}, title = {Dysbiosis is one of the risk factor for stroke and cognitive impairment and potential target for treatment.}, journal = {Pharmacological research}, volume = {164}, number = {}, pages = {105277}, doi = {10.1016/j.phrs.2020.105277}, pmid = {33166735}, issn = {1096-1186}, mesh = {Animals ; Bacterial Toxins ; Cognitive Dysfunction/*etiology/prevention &amp; control ; Dysbiosis/*complications/prevention &amp; control ; Gastrointestinal Microbiome ; Humans ; Risk Factors ; Stroke/*etiology/prevention &amp; control ; }, abstract = {More than 50 million people have various forms of cognitive impairment basically caused by neurodegenerative diseases, such as Alzheimer's, Parkinson's, and cerebrovascular diseases as well as stroke. Often these conditions coexist and exacerbate one another. The damaged area in post-stroke dementia may lead to neurodegenerative lesions. Gut microbiome functions like an endocrine organ by generating bioactive metabolites that can directly or indirectly impact human physiology. An alteration in the composition and function of intestinal flora, i.e. gut dysbiosis, is implicated in neurodegenerative and cerebrovascular diseases. Additionally, gut dysbiosis may accelerate the progression of cognitive impairment. Dysbiosis may result from obesity; metabolic disorders, cardiovascular disease, and sleep disorders, Lack of physical activity is associated with dysbiosis as well. These may coexist in various patterns in older people, enhancing the risk, incidence, and progression of cerebrovascular lesions, neurodegenerative disorders, and cognitive impairment, creating a vicious circle. Recently, it has been reported that several metabolites produced by gut microbiota (e.g., trimethylamine/trimethylamine N-oxide, short-chain fatty acids, secondary bile acids) may be linked to neurodegenerative and cerebrovascular diseases. New treatment modalities, including prebiotic and probiotics, may normalize the gut microbiota composition, change the brain-gut barrier, and decrease the risk of the pathology development. Fecal microbiota transplantation, sometimes in combination with other methods, is used for remodeling and replenishing the symbiotic gut microbiome. This promising field of research is associated with basic findings of bidirectional communication between body organs and gut microbiota that creates new possibilities of pharmacological treatments of many clinical conditions. The authors present the role of gut microbiota in physiology, and the novel therapeutic targets in modulation of intestinal microbiota Personalized therapies based on their personal genome make up could offer benefits by modulating microbiota cross-talk with brain and cardiovascular system. A healthy lifestyle, including pre and probiotic nutrition is generally recommended. Prevention may also be enhanced by correcting gut dysbiosis resulting a reduced risk of post-stroke cognitive impairment including dementia.}, }
@article {pmid33163830, year = {2020}, author = {Witjes, JJ and Smits, LP and Pekmez, CT and Prodan, A and Meijnikman, AS and Troelstra, MA and Bouter, KEC and Herrema, H and Levin, E and Holleboom, AG and Winkelmeijer, M and Beuers, UH and van Lienden, K and Aron-Wisnewky, J and Mannisto, V and Bergman, JJ and Runge, JH and Nederveen, AJ and Dragsted, LO and Konstanti, P and Zoetendal, EG and de Vos, W and Verheij, J and Groen, AK and Nieuwdorp, M}, title = {Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.}, journal = {Hepatology communications}, volume = {4}, number = {11}, pages = {1578-1590}, pmid = {33163830}, issn = {2471-254X}, abstract = {The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of . Conclusion: Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.}, }
@article {pmid33163828, year = {2020}, author = {Acharya, C and Bajaj, JS}, title = {Transmitting Diet-Related Microbial Benefit through Fecal Microbiota Transplant in NASH: Can Microbiota Cut Through the Fat?.}, journal = {Hepatology communications}, volume = {4}, number = {11}, pages = {1559-1561}, pmid = {33163828}, issn = {2471-254X}, }
@article {pmid33162889, year = {2020}, author = {Xue, A and Qian, X and Gao, X and Wang, P and Wang, L and Zheng, C and Huang, Z and Hu, W and Shi, J and Huang, Y}, title = {Fecal Microbial Signatures Are Associated With Engraftment Failure Following Umbilical Cord Blood Transplantation in Pediatric Crohn's Disease Patients With IL10RA Deficiency.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {580817}, pmid = {33162889}, issn = {1663-9812}, abstract = {OBJECTIVES: Umbilical cord blood transplantation (UCBT) is associated with a relatively high rate of engraftment failure. This study aimed at exploring whether any fecal microbiota could be associated with engraftment failure following UCBT in Crohn's disease patients with IL10RA deficiency.<br><br>METHODS: Thirteen patients were recruited and their 230 fecal samples were collected longitudinally from immediately before conditioning chemotherapy to 8 weeks post the UCBT. The V3-V4 regions of the bacterial 16S rRNA gene were amplified by PCR and sequenced, followed by bioinformatics analyses.<br><br>RESULTS: Following the UCBT, 7 out of 13 patients achieved neutrophil and platelet engraftment with a median of 21 and 28 days, respectively (S group), while 6 patients failed to achieve engraftment (F group). In comparison with that in the S group, significantly lower Shannon diversity values on the UCBT day (P = 0.0176) and less abundance of Bifidobacterium longum, Bifidobacterium pseudolongum, Enterobacteriaceae_538000, and one taxon of Lachnospiraceae family was detected in the F group, accompanied by significantly higher abundances of four taxa including Lautropia, Pseudomonas, and species Microvirgula aerodenitrificans during the chemotherapy period as well as UCBT. The abundances of thirty OTUs were correlated significantly with clinical indices.<br><br>CONCLUSIONS: Microbial indicators of reduced diversity of microbiota and signatures of specific bacterial abundances, such as a lower abundance of Bifidobacterium longum, for engraftment failure would require validation. These indicators may help for the risk stratification in patients with IL10RA deficiency undergoing UCBT.}, }
@article {pmid33162030, year = {2021}, author = {Ohsaka, F and Karatsu, Y and Kadota, Y and Tochio, T and Takemura, N and Sonoyama, K}, title = {Gut commensals suppress interleukin-2 production through microRNA-200/BCL11B and microRNA-200/ETS-1 axes in lamina propria leukocytes of murine large intestine.}, journal = {Biochemical and biophysical research communications}, volume = {534}, number = {}, pages = {808-814}, doi = {10.1016/j.bbrc.2020.10.103}, pmid = {33162030}, issn = {1090-2104}, mesh = {Animals ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Gene Expression Regulation ; Germ-Free Life ; Interleukin-2/genetics/*metabolism ; Intestine, Large/*cytology ; Leukocytes/physiology ; Male ; Mice, Inbred BALB C ; MicroRNAs/*genetics ; Proto-Oncogene Protein c-ets-1/*genetics/metabolism ; Repressor Proteins/*genetics/metabolism ; Tumor Suppressor Proteins/*genetics/metabolism ; Mice ; }, abstract = {The role of microRNAs (miRNAs) in how microbiota influence the host intestinal immune system is not fully understood. We compared the expression profiles of miRNAs and mRNAs in lamina propria leukocytes (LPL) in the large intestines of germ-free (GF) and specific pathogen-free (SPF) mice. Microarray analysis revealed different expression profiles of miRNAs and mRNAs between GF and SPF mice. Quantitative real time-PCR (qRT-PCR) showed that the level of miR-200 family members was significantly higher in SPF mice than in GF mice. In silico prediction followed by qRT-PCR suggested that Bcl11b, Ets1, Gbp7, Stat5b, and Zeb1 genes were downregulated by the miR-200 family. Western blotting revealed that the expression of BCL11B and ETS-1, but not ZEB1, in large intestinal LPL was significantly lower in SPF mice than in GF mice. Interleukin (IL)-2 production in cultured LPL upon stimulation with phorbol 12-myristate 13-acetate and ionomycin for 24 h was significantly lower in SPF mice than in GF mice. Conventionalization of GF mice substantially recapitulated SPF mice in terms of the expression of miR-200 family members and their target genes and IL-2 production in large intestinal LPL. Considering that BCL11B and ETS-1 reportedly function as transcription factors to activate the Il2 gene, we propose that the presence of gut commensals suppresses IL-2 production in large intestinal LPL, at least in part through post-transcriptional downregulation of Bcl11b and Ets1 genes by miR-200 family members.}, }
@article {pmid33160712, year = {2020}, author = {Aira, A and Arajol, C and Casals-Pascual, C and González-Suárez, B and Martí, S and Domínguez, M&#xc1; and Guardiola, J and Soriano, &#xc1; and , }, title = {Recommendations for stool donor selection for fecal microbiota transplant. Consensus document endorsed by the Catalan Society of Digestology, Catalan Society of Infectious diseases and Clinical microbiology and the GEMBIOTA group from Spanish Society of Infectious Diseases and Clinical Microbiology.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.eimc.2020.09.002}, pmid = {33160712}, issn = {2529-993X}, abstract = {Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimize the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluña with the aim of establishing recommendations for the selection of the fecal microbiota donor.}, }
@article {pmid33159374, year = {2021}, author = {Marcella, C and Cui, B and Kelly, CR and Ianiro, G and Cammarota, G and Zhang, F}, title = {Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {53}, number = {1}, pages = {33-42}, doi = {10.1111/apt.16148}, pmid = {33159374}, issn = {1365-2036}, mesh = {*Clostridioides difficile ; *Clostridium Infections/epidemiology/therapy ; Diarrhea/epidemiology/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; Incidence ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment in C. difficile infection (CDI) and is currently being investigated in other diseases. There is concern around the safety of FMT and that side effects or complications may be under-reported in the medical literature.<br><br>AIM: To evaluate the safety of FMT by summarising the overall reported Adverse Events (AEs) over a 20-year period METHODS: We searched EMBASE, MEDLINE, and Cochrane Library databases, and CNKI and Wanfang Data from January 2000 to April 2020. All original studies reporting FMT-related AEs were considered for inclusion. FMT-related AEs were further classified as delivery-related or microbiota-related.<br><br>RESULTS: Based on the inclusion criteria, 129 studies, which included 4241 patients (5688 FMT courses), were finally eligible. The most common indication for FMT was CDI. Overall, FMT-related AEs were observed in 19% of FMT procedures. The most frequently reported FMT-related AEs were diarrhoea (10%) and abdominal discomfort/pain/cramping (7%). FMT-related serious adverse events (SAEs), including infections and deaths, have been reported in 1.4% of patients who underwent FMT (0.99% microbiota-related SAEs). Four of five FMT-related deaths were reported in patients receiving FMT via the upper gastrointestinal route. Importantly, all reported FMT-related SAEs were in patients with mucosal barrier injury.<br><br>CONCLUSION: Most FMT-related AEs were mild or moderate and self-limiting. Although FMT appears to be highly safe, its methodology should be improved to reduce both delivery-related AEs and, microbiota-related AEs.}, }
@article {pmid33159210, year = {2021}, author = {Zellmer, C and Sater, MRA and Huntley, MH and Osman, M and Olesen, SW and Ramakrishna, B}, title = {Shiga Toxin-Producing Escherichia coli Transmission via Fecal Microbiota Transplant.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {72}, number = {11}, pages = {e876-e880}, doi = {10.1093/cid/ciaa1486}, pmid = {33159210}, issn = {1537-6591}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; *Escherichia coli Infections ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; *Shiga-Toxigenic Escherichia coli ; }, abstract = {Fecal microbiota transplantation (FMT) is recommended therapy for multiply recurrent Clostridioides difficile infection. We report adverse events in 7 patients who received FMT from a stool donor who was colonized with Shiga toxin-producing Escherichia coli (STEC). No patients died of FMT-transmitted STEC. Improved screening can likely avoid future transmission.}, }
@article {pmid33158078, year = {2020}, author = {Souai, N and Zidi, O and Mosbah, A and Kosai, I and Manaa, JE and Mokhtar, NB and Asimakis, E and Stathopoulou, P and Cherif, A and Tsiamis, G and Kouidhi, S}, title = {Impact of the Post-Transplant Period and Lifestyle Diseases on Human Gut Microbiota in Kidney Graft Recipients.}, journal = {Microorganisms}, volume = {8}, number = {11}, pages = {}, pmid = {33158078}, issn = {2076-2607}, support = {KA107//Erasmus+/ ; }, abstract = {Gaining long-term graft function and patient life quality remain critical challenges following kidney transplantation. Advances in immunology, gnotobiotics, and culture-independent molecular techniques have provided growing insights into the complex relationship of the microbiome and the host. However, little is known about the over time-shift of the gut microbiota in the context of kidney transplantation and its impact on both graft and health stability. Here we aimed to characterize the structure of gut microbiota within stable kidney graft recipients. We enrolled forty kidney transplant patients after at least three months of transplantation and compared them to eighteen healthy controls. The overall microbial community structure of the kidney transplanted group was clearly different from control subjects. We found lower relative abundances of Actinobacteria, Bacteroidetes, and Verrucomicrobia within the patient group and a higher abundance of Proteobacteria compared to the control group. Both richness and Shannon diversity indexes were significantly lower in the kidney graft recipients than in healthy controls. Post-graft period was positively correlated with the relative abundance of the Proteobacteria phylum, especially Escherichia.Shigella genus. Interestingly, only Parabacteroides was found to significantly differentiate patients that were not suffering from lifestyle diseases and those who suffer from post-graft complications. Furthermore, network analysis showed that the occurrence of lifestyle diseases was significantly linked with a higher number of negative interactions of Sutterella and Succinivibrio genera within patients. This study characterizes gut microbiome fluctuation in stable kidney transplant patients after a long post-allograft period. Analysis of fecal microbiota could be useful for nephrologists as a new clinical tool that can improve kidney allograft monitoring and outcomes.}, }
@article {pmid33156122, year = {2021}, author = {Adelman, MW and Woodworth, MH and Shaffer, VO and Martin, GS and Kraft, CS}, title = {Critical Care Management of the Patient with Clostridioides difficile.}, journal = {Critical care medicine}, volume = {49}, number = {1}, pages = {127-139}, pmid = {33156122}, issn = {1530-0293}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; Clostridium Infections/diagnosis/etiology/prevention &amp; control/*therapy ; Critical Care/*methods ; Fecal Microbiota Transplantation ; Humans ; Risk Factors ; }, abstract = {OBJECTIVES: To review published clinical evidence on management of Clostridioides difficile infection in critically ill patients.<br><br>DATA SOURCES: We obtained relevant studies from a PubMed literature review and bibliographies of reviewed articles.<br><br>STUDY SELECTION: We selected English-language studies addressing aspects of C. difficile infection relevant to critical care clinicians including epidemiology, risk factors, diagnosis, treatment, and prevention, with a focus on high-quality clinical evidence.<br><br>DATA EXTRACTION: We reviewed potentially relevant studies and abstracted information on study design, methods, patient selection, and results of relevant studies. This is a synthetic (i.e., not systematic) review.<br><br>DATA SYNTHESIS: C. difficile infection is the most common healthcare-associated infection in the United States. Antibiotics are the most significant C. difficile infection risk factor, and among antibiotics, cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam confer the highest risk. Age, diabetes mellitus, inflammatory bowel disease, and end-stage renal disease are risk factors for C. difficile infection development and mortality. C. difficile infection diagnosis is based on testing appropriately selected patients with diarrhea or on clinical suspicion for patients with ileus. Patients with fulminant disease (C. difficile infection with hypotension, shock, ileus, or megacolon) should be treated with oral vancomycin and IV metronidazole, as well as rectal vancomycin in case of ileus. Patients who do not respond to initial therapy should be considered for fecal microbiota transplant or surgery. Proper infection prevention practices decrease C. difficile infection risk.<br><br>CONCLUSIONS: Strong clinical evidence supports limiting antibiotics when possible to decrease C. difficile infection risk. For patients with fulminant C. difficile infection, oral vancomycin reduces mortality, and adjunctive therapies (including IV metronidazole) and interventions (including fecal microbiota transplant) may benefit select patients. Several important questions remain regarding fulminant C. difficile infection management, including which patients benefit from fecal microbiota transplant or surgery.}, }
@article {pmid33155639, year = {2021}, author = {Allegretti, JR and Kelly, CR and Grinspan, A and Mullish, BH and Hurtado, J and Carrellas, M and Marcus, J and Marchesi, JR and McDonald, JAK and Gerardin, Y and Silverstein, M and Pechlivanis, A and Barker, GF and Miguens Blanco, J and Alexander, JL and Gallagher, KI and Pettee, W and Phelps, E and Nemes, S and Sagi, SV and Bohm, M and Kassam, Z and Fischer, M}, title = {Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection.}, journal = {Inflammatory bowel diseases}, volume = {27}, number = {9}, pages = {1371-1378}, pmid = {33155639}, issn = {1536-4844}, support = {21228/VAC_/Versus Arthritis/United Kingdom ; MR/P028225/1/MRC_/Medical Research Council/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; P30 DK034854/DK/NIDDK NIH HHS/United States ; }, mesh = {Clostridioides difficile ; *Clostridium Infections/therapy ; *Colitis, Ulcerative/therapy ; *Crohn Disease/therapy ; *Fecal Microbiota Transplantation ; Humans ; Prospective Studies ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited.<br><br>METHODS: Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling.<br><br>RESULTS: Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 &#xb1; 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 &#xb1; 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04).<br><br>CONCLUSION: This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.}, }
@article {pmid33155247, year = {2020}, author = {Kaźmierczak-Siedlecka, K and Vitale, E and Makarewicz, W}, title = {COVID-19 - gastrointestinal and gut microbiota-related aspects.}, journal = {European review for medical and pharmacological sciences}, volume = {24}, number = {20}, pages = {10853-10859}, doi = {10.26355/eurrev_202010_23448}, pmid = {33155247}, issn = {2284-0729}, mesh = {COVID-19 ; Coronavirus Infections/*microbiology ; Diarrhea/virology ; Feces/virology ; Gastrointestinal Diseases/*microbiology/virology ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology/virology ; Humans ; Pandemics ; Pneumonia, Viral/*microbiology ; Severity of Illness Index ; Vomiting/virology ; }, abstract = {OBJECTIVE: The aim of this review paper was to discuss the gut microbiota-related aspects of COVID-19 patients. We presented the faecal-oral transmission of SARS-CoV-2, gut microbiota imbalance, and fecal microbiota transplantation as a hidden source of this virus.<br><br>MATERIALS AND METHODS: We analyzed the available literature (PubMed, Embase, Google Scholar databases) regarding COVID-19 and gut microbiota related aspects.<br><br>RESULTS: The gastrointestinal symptoms, such as nausea, vomiting, diarrhea, abdominal discomfort/pain, may occur in these patients. Notably, these symptoms may contribute to the severity of COVID-19. Recent several studies have revealed a new SARS-CoV-2 transmission possibility, opening a fresh view on COVID-19. It is observed the possibility of SARS-CoV-2 transmission via faecal-oral route. Fecal microbiota transplantation may be a hidden source of SARS-CoV-2. Additionally, the pharmacological treatment of COVID-19 and other factors may significantly alter the composition of gut microbiota. Among others, loss of bacterial diversity, the decrease of commensal microbes as well as the increase of opportunistic pathogens are observed.<br><br>CONCLUSIONS: The alterations of gut microbiota in COVID-19 patients consequently may lead to the development of gut dysbiosis-related diseases even after recovery from COVID-19. Therefore, it is recommended to screen stool samples taken from recovered patients at least 35 days after clearance of virus from respiratory tract. Before 35 days period, SARS-CoV-2 may still be detected in feces. It is also recommended to screen the composition as well as the activity of gut microbiota to assess its balance. In the case of gut dysbiosis, there should be introduced an appropriate method of its modulation. Additionally, all the fecal samples which are prepared for fecal microbiota transplantation should be tested for SARS-CoV-2 to provide protection for its recipients.}, }
@article {pmid33153085, year = {2020}, author = {Borsom, EM and Lee, K and Cope, EK}, title = {Do the Bugs in Your Gut Eat Your Memories? Relationship between Gut Microbiota and Alzheimer's Disease.}, journal = {Brain sciences}, volume = {10}, number = {11}, pages = {}, pmid = {33153085}, issn = {2076-3425}, support = {CTR040636//Arizona Alzheimer's Consortium DHS/ ; }, abstract = {The human microbiota is composed of trillions of microbial cells inhabiting the oral cavity, skin, gastrointestinal (GI) tract, airways, and reproductive organs. The gut microbiota is composed of dynamic communities of microorganisms that communicate bidirectionally with the brain via cytokines, neurotransmitters, hormones, and secondary metabolites, known as the gut microbiota-brain axis. The gut microbiota-brain axis is suspected to be involved in the development of neurological diseases, including Alzheimer's disease (AD), Parkinson's disease, and Autism Spectrum Disorder. AD is an irreversible, neurodegenerative disease of the central nervous system (CNS), characterized by amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Microglia and astrocytes, the resident immune cells of the CNS, play an integral role in AD development, as neuroinflammation is a driving factor of disease severity. The gut microbiota-brain axis is a novel target for Alzheimer's disease therapeutics to modulate critical neuroimmune and metabolic pathways. Potential therapeutics include probiotics, prebiotics, fecal microbiota transplantation, and dietary intervention. This review summarizes our current understanding of the role of the gut microbiota-brain axis and neuroinflammation in the onset and development of Alzheimer's disease, limitations of current research, and potential for gut microbiota-brain axis targeted therapies.}, }
@article {pmid33151664, year = {2020}, author = {Shi, L and Zheng, J and Yan, S and Li, Y and Wang, Y and Liu, X and Xiao, C}, title = {Exposure to Perfluorooctanoic Acid Induces Cognitive Deficits via Altering Gut Microbiota Composition, Impairing Intestinal Barrier Integrity, and Causing Inflammation in Gut and Brain.}, journal = {Journal of agricultural and food chemistry}, volume = {68}, number = {47}, pages = {13916-13928}, doi = {10.1021/acs.jafc.0c05834}, pmid = {33151664}, issn = {1520-5118}, mesh = {Animals ; Brain ; Caprylates/toxicity ; Cognition ; *Fluorocarbons/toxicity ; *Gastrointestinal Microbiome ; Inflammation/chemically induced ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {Perfluorooctanoic acid (PFOA) is an eight-carbon perfluoroalkyl chemical and has been detected widely in many media. Although the toxic effect of PFOA has been confirmed, the influence on gut and brain has not been cleared. Male C57BL/6J mice were exposed to different concentrations (0, 0.5, 1, and 3 mg/Kg (bw)/day of PFOA for 35 days in this work. The results indicate that exposure to PFOA could damage intestinal barrier integrity and impair the synaptic structure. PFOA exposure also caused inflammation in gut and brain by increasing lipopolysaccharide, tumor necrosis factor-α, interleukin-1 beta, and cyclooxygenase-2 and decreasing interleukin-10. Interestingly, fecal microbiota transplantation treatment could attenuate a series of PFOA-induced changes to a certain extent. The results suggest that exposure to PFOA has potential deleterious effects on gut and brain, and inflammation may play an essential role in evaluating the influence induced by PFOA exposure.}, }
@article {pmid33151137, year = {2021}, author = {Keller, JJ and Ooijevaar, RE and Hvas, CL and Terveer, EM and Lieberknecht, SC and Högenauer, C and Arkkila, P and Sokol, H and Gridnyev, O and Mégraud, F and Kump, PK and Nakov, R and Goldenberg, SD and Satokari, R and Tkatch, S and Sanguinetti, M and Cammarota, G and Dorofeev, A and Gubska, O and Ianiro, G and Mattila, E and Arasaradnam, RP and Sarin, SK and Sood, A and Putignani, L and Alric, L and Baunwall, SMD and Kupcinskas, J and Link, A and Goorhuis, AG and Verspaget, HW and Ponsioen, C and Hold, GL and Tilg, H and Kassam, Z and Kuijper, EJ and Gasbarrini, A and Mulder, CJJ and Williams, HRT and Vehreschild, MJGT}, title = {A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group.}, journal = {United European gastroenterology journal}, volume = {9}, number = {2}, pages = {229-247}, pmid = {33151137}, issn = {2050-6414}, support = {PB-PG-0418-20007/DH_/Department of Health/United Kingdom ; }, mesh = {Age Factors ; Biological Specimen Banks/*organization &amp; administration/standards ; Clostridioides difficile ; Clostridium Infections/immunology/therapy ; Contraindications, Procedure ; Donor Selection ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Feces ; Humans ; Immunocompromised Host ; Informed Consent ; Quality Assurance, Health Care ; Recurrence ; Specimen Handling ; }, abstract = {BACKGROUND: Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.<br><br>OBJECTIVE: Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.<br><br>METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation.<br><br>RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.<br><br>CONCLUSION: The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.}, }
@article {pmid33145316, year = {2020}, author = {Wang, D and Hao, H and Li, X and Wang, Z}, title = {The effect of intestinal flora on immune checkpoint inhibitors in tumor treatment: a narrative review.}, journal = {Annals of translational medicine}, volume = {8}, number = {17}, pages = {1097}, pmid = {33145316}, issn = {2305-5839}, abstract = {Tremendous progress has been achieved in understanding of the interaction between tumor microenvironment and intestinal flora in the past decades. Immune checkpoint inhibitors (ICIs) are a promising treatment strategy for advanced tumors, most prominently cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed cell death protein-1 (PD-1), its major ligand PD-L1, its beneficial to part of the population and obtaining excellent clinical results. However, the majority of patients do not respond or develop early progressive disease. Reached consensus by experts currently believe that the intestinal flora plays an important role in the explanation of the limited therapeutic effect of ICIs, there are differences in the composition of intestinal flora between patients with good response and patients with poor response, cloned mice by fecal microbiota transplantation (FMT) proved that the mice with transplanted feces from patients with good response can reduce tumor volume and obtain a better progress free survival (PFS). Therefore, "beneficial bacteria" seem to be enriched in the intestinal flora of patients who are well-responsive to ICIs and can be potentially used as a marker and cancer immunotherapeutic adjuvant of ICIs. In this review, we aim to summarize some of the studies demonstrating intestinal flora on tumor immunotherapy through anti-PD1, anti-PD-L1, anti-CTLA-4 and discuss possible mechanisms of this effect.}, }
@article {pmid33142068, year = {2020}, author = {Holster, S and Rode, J and Bohr, J and Kumawat, AK and Veress, G and Hultgren Hörnquist, E and Brummer, RJ and König, J}, title = {Faecal microbiota transfer in patients with microscopic colitis - a pilot study in collagenous colitis.}, journal = {Scandinavian journal of gastroenterology}, volume = {55}, number = {12}, pages = {1454-1466}, doi = {10.1080/00365521.2020.1839544}, pmid = {33142068}, issn = {1502-7708}, mesh = {*Colitis, Collagenous/therapy ; *Colitis, Ulcerative ; Feces ; Humans ; *Microbiota ; Pilot Projects ; Quality of Life ; }, abstract = {OBJECTIVES: Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of patients with the aim to restore a disturbed gut microbiota.<br><br>METHODS: In this pilot study (NCT03275467), the effect of three repeated FMTs (day 0, two weeks, four weeks) was studied and followed up for six months in nine collagenous colitis (CC) patients, using two stool donors.<br><br>RESULTS: Five patients had an active disease at the time of baseline sampling. The primary endpoint (remission at six weeks, defined as <3 stools whereof <1 watery stool per day) was achieved by two of these patients, and by one at eight weeks. Overall, in all nine patients, FMT did not result in a significant reduction of watery stools, assessed by daily diary. However, diarrhoea (assessed by gastrointestinal symptom rating scale) was significantly improved at four (p&#x2009;=&#x2009;.038) and eight weeks (p&#x2009;=&#x2009;.038), indigestion at eight (p&#x2009;=&#x2009;.045) and 12 weeks (p&#x2009;=&#x2009;.006), disease-related worries at four (p&#x2009;=&#x2009;.027) and eight weeks (p&#x2009;=&#x2009;.027), and quality of life at six months (p&#x2009;=&#x2009;.009). FMT resulted in an increased number of lamina propria lymphocytes, possibly indicating an initial mucosal immune activation. No serious adverse events, no systemic effects, and no changes in faecal calprotectin and psychological symptoms were observed.<br><br>CONCLUSIONS: FMT is able to improve symptoms in a yet undefined subset of CC patients. Further studies could help to characterise this subset and to understand if these results can be generalised to all microscopic colitis patients.}, }
@article {pmid33139601, year = {2020}, author = {Gesualdo, M and Rizzi, F and Bonetto, S and Rizza, S and Cravero, F and Saracco, GM and De Angelis, CG}, title = {Pancreatic Diseases and Microbiota: A Literature Review and Future Perspectives.}, journal = {Journal of clinical medicine}, volume = {9}, number = {11}, pages = {}, pmid = {33139601}, issn = {2077-0383}, abstract = {Gut microbiota represent an interesting worldwide research area. Several studies confirm that microbiota has a key role in human diseases, both intestinal (such as inflammatory bowel disease, celiac disease, intestinal infectious diseases, irritable bowel syndrome) and extra intestinal disorders (such as autism, multiple sclerosis, rheumatologic diseases). Nowadays, it is possible to manipulate microbiota by administering prebiotics, probiotics or synbiotics, through fecal microbiota transplantation in selected cases. In this scenario, pancreatic disorders might be influenced by gut microbiota and this relationship could be an innovative and inspiring field of research. However, data are still scarce and controversial. Microbiota manipulation could represent an important therapeutic strategy in the pancreatic diseases, in addition to standard therapies. In this review, we analyze current knowledge about correlation between gut microbiota and pancreatic diseases, by discussing on the one hand existing data and on the other hand future possible perspectives.}, }
@article {pmid33139129, year = {2021}, author = {Sterpetti, AV and Marzo, LD and Sapienza, P}, title = {Risk factors for adenocarcinoma in the surgically transposed colon not exposed to the fecal stream. Etiological considerations extrapolated to sporadic colon carcinoma in the general population.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {47}, number = {5}, pages = {931-934}, doi = {10.1016/j.ejso.2020.10.026}, pmid = {33139129}, issn = {1532-2157}, mesh = {Adenocarcinoma/*etiology ; Adult ; Aged ; Aged, 80 and over ; Colon/*transplantation ; Colonic Neoplasms/*etiology ; Feces ; Female ; Gastrectomy ; Humans ; Inflammation/complications ; Male ; Middle Aged ; Risk Factors ; Vagina/surgery ; }, abstract = {BACKGROUND: The aim of the study was to analyze the clinical characteristics and outcomes of patients with de novo secondary adenocarcinoma arising in the operatively transposed colon not exposed to the fecal stream.<br><br>METHODS: Two investigators collected and reviewed papers from June 1938 to June 2019, reporting patients with adenocarcinoma arising in the transposed colon, not in contact with the fecal stream.<br><br>RESULTS: Overall, we identified 98 patients with a transposed colonic autograft, positioned as conduit but not in contact with the fecal stream, in whom a secondary de novo adenocarcinoma was diagnosed. In 50% of the patients, the secondary adenocarcinoma was diagnosed at an advanced stage, with a subsequent poor clinical outcome. Earlier diagnosis allowed local resection with long term success. The occurrence of the adenocarcinoma appeared to be closely related to aging, and to clinical evidence of chronic inflammation.<br><br>CONCLUSIONS: Patients in whom the colon has been surgically transposed to different anatomic positions, away from the fecal stream, can develop a secondary colonic adenocarcinoma with. Aging and chronic inflammation seem to be risk factors for a secondary adenocarcinoma more than time from implant. Screening for polyps and adenocarcinomas in these patients should be considered.}, }
@article {pmid33136284, year = {2020}, author = {Gomaa, EZ}, title = {Human gut microbiota/microbiome in health and diseases: a review.}, journal = {Antonie van Leeuwenhoek}, volume = {113}, number = {12}, pages = {2019-2040}, doi = {10.1007/s10482-020-01474-7}, pmid = {33136284}, issn = {1572-9699}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; *Microbiota ; *Probiotics ; }, abstract = {The human gut microbiota has received considerable interest in the recent years and our knowledge of the inhabitant species and their potential applications is increased particularly after the development of metagenomic studies. Gut microbiota is highly diverse and harboring trillions of microorganisms in human digestive system. The shaping and multiplication of gut microbiome starts at birth, while the modification of their composition depends mainly on various genetic, nutritional and environmental factors. The modification in the composition and function of the gut microbiota can change intestinal permeability, digestion and metabolism as well as immune responses. The pro inflammatory state caused by alternation of gut microbiota balance lead to the onset of many diseases ranging from gastrointestinal and metabolic conditions to immunological and neuropsychiatric diseases. In this context, the present review clarifies the role of gut microbiota in maintaining host health and investigates how nutritional and environmental factors affect the gut microbial structure and function. In addition, many therapeutic strategies of gut microbiota aimed at modulating and restoring of the intestinal ecosystem balance have been surveyed.}, }
@article {pmid33136261, year = {2021}, author = {Aira, A and Rubio, E and Vergara Gómez, A and Fehér, C and Casals-Pascual, C and González, B and Morata, L and Rico, V and Soriano, A}, title = {rUTI Resolution After FMT for Clostridioides difficile Infection: A Case Report.}, journal = {Infectious diseases and therapy}, volume = {10}, number = {2}, pages = {1065-1071}, pmid = {33136261}, issn = {2193-8229}, abstract = {Clostridioides difficile infection (CDI) is the leading cause of nosocomial infectious diarrhea. Fecal microbiota transplantation (FMT) is a successful treatment for recurrent CDI (rCDI), and in some patients FMT has been associated with the resolution of recurrent urinary tract infections (rUTI). Recent evidence suggests that the origin of most bacterial infections in the urinary tract is the gut. Thus, the possibility of using FMT to displace pathogens commonly involved in rUTIs has major therapeutic implications. We report the case of a 93-year-old female patient with a rCDI and rUTI that underwent FMT and reported a complete clinical resolution of CDI; unexpectedly, no new symptomatic UTI episodes were diagnosed post-FMT. We characterized the gut microbiota of the stool donor and of the patient before and after the procedure. Our patient presented a dysbiosis with clear predominance of Enterobacteriaceae (74%) before FMT, which was significantly reduced to 0.07% after FMT. These findings were maintained for almost a year. We also observed an increase in microbial diversity indices compared with the pre-FMT sample reaching diversity values comparable to the donor stool samples. We reasoned that the disappearance of UTIs in our patient resulted from the reduction of Enterobacteriaceae in the gut microbiota. Our findings support previous evidence suggesting the potential of FMT for rUTI, particularly in cases due to multi-drug resistant pathogens where conventional antibiotic treatment is not an option.}, }
@article {pmid33134739, year = {2020}, author = {Dong, LT and Espinoza, HV and Espinoza, JL}, title = {Emerging superbugs: The threat of Carbapenem Resistant Enterobacteriaceae.}, journal = {AIMS microbiology}, volume = {6}, number = {3}, pages = {176-182}, pmid = {33134739}, issn = {2471-1888}, abstract = {Carbapenem-resistant Enterobacteriaceae (CRE) are gram-negative bacteria that are resistant to carbapenems, a group of antibiotics considered as the last-resource for the treatment of infections caused by multidrug-resistant bacteria. CRE constitutes a major threat to health care systems because infections caused by these pathogens are difficult to treat and are commonly associated with high mortality due to the limited availability of effective antibiotics. While infection prevention and timely detection are of vital importance to control CRE infections, developing new and effective anti-CRE therapies is also crucial. Accumulating evidence indicates that gut microbiota alteration (dysbiosis) is associated with an increased intestinal colonization with CRE and consequently with higher risk of developing CRE infections. Importantly, therapeutic interventions aimed to modify the gut microbiota composition via fecal microbiota transplantation (FMT) have been explored in various clinical settings with some of them showing promising results, although larger clinical trials are needed to confirm the efficacy of this strategy. Here, we highlight the challenges associated with the emergence of CRE infections.}, }
@article {pmid33133183, year = {2020}, author = {Ye, ZN and Xia, HH and Zhang, R and Li, L and Wu, LH and Liu, XJ and Xie, WR and He, XX}, title = {The Efficacy of Washed Microbiota Transplantation on Helicobacter pylori Eradication: A Pilot Study.}, journal = {Gastroenterology research and practice}, volume = {2020}, number = {}, pages = {8825189}, pmid = {33133183}, issn = {1687-6121}, abstract = {AIM: The fecal microbiota transplantation by washed preparation was recently coined as washed microbiota transplantation (WMT). This pilot study is aimed at exploring the feasibility and efficacy of WMT on Helicobacter pylori eradication.<br><br>METHODS: Consecutive patients who had been treated with WMT for various indications and who were positive for H. pylori infection before WMT treatment but had never received eradication therapy for H. pylori infection were invited to take a follow-up [13]C-urea breath test. The associations of demographic, clinical factors, and laboratory indicators for gastric function and intestinal barrier function with the therapeutic effect were determined.<br><br>RESULTS: A total of 32 eligible patients were included, and the overall H. pylori eradication rate was 40.6% (13/32). Patients with H. pylori eradication had a higher pepsinogen ratio (PGR) than those without (13.00 &#xb1; 6.97vs.8.31 &#xb1; 3.733; P = 0.02). Female patients had a higher, albeit not statistically significant, eradication rate than male patients (53.85% vs. 31.58%; P = 0.208). Compared with lower gastrointestinal tract delivery route, middle gastrointestinal tract delivery route seems to be a more suitable way for the treatment of H. pylori infection (58.33% vs 16.67%; P = 0.152). There was no significant difference in other demographic and clinical factors between patients with and without H. pylori eradication.<br><br>CONCLUSION: H. pylori infection is eradicated in a proportion of patients who have received WMT. An increased pre-WMT PGR appears to be associated with the therapeutic effect. Further studies are required to confirm the efficacy of WMT, especially in combination with currently recommended regimens in randomized controlled trials.}, }
@article {pmid33132658, year = {2020}, author = {Wen, Q and Liu, KJ and Cui, BT and Li, P and Wu, X and Zhong, M and Wei, L and Tu, H and Yuan, Y and Lin, D and Hsu, WH and Wu, DC and Yin, H and Zhang, FM}, title = {Impact of cap-assisted colonoscopy during transendoscopic enteral tubing: A randomized controlled trial.}, journal = {World journal of gastroenterology}, volume = {26}, number = {39}, pages = {6098-6110}, pmid = {33132658}, issn = {2219-2840}, mesh = {Adult ; *Cecum/diagnostic imaging ; *Colitis, Ulcerative ; Colonoscopy ; Humans ; Prospective Studies ; }, abstract = {BACKGROUND: Colonic transendoscopic enteral tubing (TET) requires double cecal intubation, raising a common concern of how to save cecal intubation time and make the tube stable. We hypothesized that cap-assisted colonoscopy (CC) might reduce the second cecal intubation time and bring potential benefits during the TET procedure.<br><br>AIM: To investigate if CC can decrease the second cecal intubation time compared with regular colonoscopy (RC).<br><br>METHODS: This prospective multicenter, randomized controlled trial was performed at four centers. Subjects &#x2265; 7 years needing colonic TET were recruited from August 2018 to January 2020. All subjects were randomly assigned to two groups. The primary outcome was the second cecal intubation time. Secondary outcomes included success rate, insertion pain score, single clip fixation time, purpose and retention time of TET tube, length of TET tube inserted into the colon, and all procedure-related (serious) adverse events.<br><br>RESULTS: A total of 331 subjects were randomized to the RC (n = 165) or CC (n = 166) group. The median time of the second cecal intubation was significantly shorter for CC than RC (2.2 min vs 2.8 min, P < 0.001). In patients with constipation, the median time of second cecal intubation in the CC group (n = 50) was shorter than that in the RC group (n = 43) (2.6 min vs 3.8 min, P = 0.004). However, no difference was observed in the CC (n = 42) and RC (n = 46) groups of ulcerative colitis patients (2.0 min vs 2.5 min, P = 0.152). The insertion pain score during the procedure in CC (n = 14) was lower than that in RC (n = 19) in unsedated colonoscopy (3.8 &#xb1; 1.7 vs 5.4 &#xb1; 1.9; P = 0.015). Multivariate analysis revealed that only CC (odds ratio [OR]: 2.250, 95% confidence interval [CI]: 1.161-4.360; P = 0.016) was an independent factor affecting the second cecal intubation time in difficult colonoscopy. CC did not affect the colonic TET tube's retention time and length of the tube inserted into the colon. Moreover, multivariate analysis found that only endoscopic clip number (OR: 2.201, 95%CI: 1.541-3.143; P < 0.001) was an independent factor affecting the retention time. Multiple regression analysis showed that height (OR: 1.144, 95%CI: 1.027-1.275; P = 0.014) was the only independent factor influencing the length of TET tube inserted into the colon in adults.<br><br>CONCLUSION: CC for colonic TET procedure is a safe and less painful technique, which can reduce cecal intubation time.}, }
@article {pmid33131919, year = {2021}, author = {Chaitman, J and Gaschen, F}, title = {Fecal Microbiota Transplantation in Dogs.}, journal = {The Veterinary clinics of North America. Small animal practice}, volume = {51}, number = {1}, pages = {219-233}, doi = {10.1016/j.cvsm.2020.09.012}, pmid = {33131919}, issn = {1878-1306}, mesh = {Animals ; Clostridium Infections/therapy/*veterinary ; Dog Diseases/*therapy ; Dogs ; Dysbiosis/therapy/*veterinary ; Fecal Microbiota Transplantation/*veterinary ; Gastrointestinal Microbiome ; }, abstract = {In people, fecal microbiota transplantation is recognized as the best treatment modality for recurrent Clostridioides difficile infection in people, and its value is currently investigated in the treatment of other diseases associated with an abnormal gut microbiome. In dogs, intestinal dysbiosis has been documented in many acute and chronic digestive diseases as well as in diseases of other organ systems. There are only few published studies evaluating the benefits of fecal microbiota transplantation (FMT) in canine gastrointestinal disorders. They provide evidence that FMT may be beneficial in the treatment of acute intestinal diseases and hope that the technique might also be useful for the management of chronic enteropathies.}, }
@article {pmid33131263, year = {2020}, author = {Merli, P and Putignani, L and Ruggeri, A and Del Chierico, F and Gargiullo, L and Galaverna, F and Gaspari, S and Pagliara, D and Russo, A and Pane, S and Strocchio, L and Algeri, M and Rea, F and Francesca Romeo, E and Bernaschi, P and Onetti Muda, A and Dallapiccola, B and Locatelli, F}, title = {Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes.}, journal = {Haematologica}, volume = {105}, number = {11}, pages = {2686-2690}, pmid = {33131263}, issn = {1592-8721}, mesh = {Bacteria ; Child ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Humans ; *Pharmaceutical Preparations ; }, }
@article {pmid33130602, year = {2020}, author = {Nagy, GG and Tudlik, Z and Gergely, L and Kónya, J and Orosi, P and Rákóczi, &#xc9; and Szabó, J and Várvölgyi, C and Vitális, E and Paragh, G}, title = {[Reconsidering the technical aspects and quality management background of faecal microbiota transplantation due to the novel coronavirus pandemic].}, journal = {Orvosi hetilap}, volume = {161}, number = {44}, pages = {1858-1871}, doi = {10.1556/650.2020.32023}, pmid = {33130602}, issn = {1788-6120}, mesh = {Betacoronavirus ; COVID-19 ; Clostridioides difficile ; Clostridium Infections/*therapy ; *Coronavirus ; Coronavirus Infections/epidemiology/*prevention &amp; control ; Fecal Microbiota Transplantation/methods/*standards ; Humans ; Hungary ; Pandemics ; Pneumonia, Viral/epidemiology/*prevention &amp; control ; Quality Improvement ; SARS-CoV-2 ; Treatment Outcome ; }, abstract = {Összefoglaló. A székletmikrobiota-transzplantáció (faecalismikrobiota-transzplantáció - FMT) a Clostridioides difficile fertőzés (CDI) kezelésében nemzetközileg széles körben elfogadott, megfelelő szakmai háttér mellett végezve biztonságos, potenciálisan életmentő, költséghatékony, valamint a hospitalizációs idő és az orvos-beteg találkozások jelentős redukálására képes eljárás. Az FMT elvégzésére egyes országokban magas szintű minőségirányítási háttérrel működő, célfeladatra szerveződött donor- és székletbankok rendezkedtek be. Máshol, így például hazánkban, az eljáráshoz az egyértelmű jogi szabályozási környezet, a standardizált technológiai háttér és a finanszírozás hiánya miatt nem egységes a hozzáférés. Régóta időszerű továbbá, hogy a heterogén, nemegyszer háztartási eszközökkel előkészített beavatkozások helyett a nemzetközi és legújabban már a hazai ajánlásokban is megfogalmazott, a betegbiztonságot legjobban garantáló elvárások mellett történjen a széklettranszplantáció. Az új koronavírus (SARS-CoV-2) okozta pandémia megjelenése erőteljes szakmai érv országos szinten az FMT minőségirányítási környezetének és technológiai hátterének újragondolására, mert a SARS-CoV-2 egyszerre jelent kockázatot a CDI miatt kórházban kezelt sérülékeny betegpopulációnak, és egyben veszélyezteti az FMT biztonságosságát mind a recipiens, mind pedig az eljárást végző egészségügyi személyzet tekintetében. Ezekre a szakmai és társadalmi kihívásokra reagálva, a széles körű beteghozzáférés és a legmagasabb szintű betegbiztonság garantálására, a Debreceni Egyetemen új eljárásrendet dolgoztunk ki az FMT végzésére. Ezen eljárásrendnek a COVID-19-pandémia miatt módosított, a fagyasztottgraftbank üzemeltetése és a rendszerszemlélet tekintetében releváns elemeit ismertetjük. Javasolt, hogy országos szinten hasonló, megfelelő minőségirányítási és technológiai környezettel, a SARS-CoV-2-fertőzés kizárását is integráló donorszűrési rendszerrel, továbbá fagyasztottgraft-banki háttérrel működő laboratóriumok vegyenek részt a széklettranszplantációk végzésében. Felmerül továbbá, hogy az eljárást a számos analógia és a donor-recipiens koncepció alapján a sejt- és szövettranszplantációkra vonatkozó szabályozórendszer keretei közé ajánlott beágyazni. Orv Hetil. 2020; 161(44): 1858-1871. Summary. Stool transplantation (faecal microbiota transplantation - FMT) is a widely accepted, potentially life-saving, cost-effective medical intervention for the treatment of Clostridioides difficile infection (CDI), which has an acceptable safety profile if performed with an appropriate professional background. FMT can significantly reduce hospitalization time and the number of patient visits. National donor and stool banks with high-standard quality management systems were established in certain countries for supporting the procedures. In other regions, including Hungary, patient access is not uniform due to the lack of clear legal regulations, standardized technology or financial reimbursement. It has been expected for a long time to replace the heterogenous techniques, occasionally utilizing household equipment with a technology providing improved patient safety and fulfilling international and recently published local FMT guidelines. The emergence of the novel coronavirus (SARS-CoV-2) pandemic is a very powerful argument in favour of urgently reconsidering the quality management and technological background of FMT procedures. SARS-CoV-2 is a major threat to the vulnerable patients suffering from CDI and also impose risks for the recipient and healthcare personnel involved in carrying out the transplantation. New FMT guidelines were implemented at the University of Debrecen to address these professional and public challenges, to provide wide patient access and to guarantee the highest achievable patient safety. Relevant elements of this new protocol are presented, focusing on a systemic quality management approach, on the operation of a frozen stool bank and on a modified donor screening algorithm taking the risks of COVID-19 into consideration. We suggest that laboratories with proper quality assurance and technological conditions, implementing SARS-CoV-2 donor screening and operating a frozen graft bank should participate in faecal microbiota transplantations. It is also recommended that, based on the analogies and the similar donor-recipient concept, FMT should be embedded under the organ tissue and cell transplantation polices in Hungary. Orv Hetil. 2020; 161(44): 1858-1871.}, }
@article {pmid33128055, year = {2021}, author = {Maillard, A and Scemla, A and Laffy, B and Mahloul, N and Molina, JM}, title = {Safety and efficacy of fumagillin for the treatment of intestinal microsporidiosis. A French prospective cohort study.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {76}, number = {2}, pages = {487-494}, doi = {10.1093/jac/dkaa438}, pmid = {33128055}, issn = {1460-2091}, mesh = {Child ; *Cyclohexanes/adverse effects ; Fatty Acids, Unsaturated ; Feces ; France ; Humans ; *Microsporidiosis/drug therapy ; Prospective Studies ; Sesquiterpenes ; }, abstract = {BACKGROUND: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a cause of chronic diarrhoea in immunocompromised patients. Fumagillin has been approved in France for its treatment.<br><br>OBJECTIVES: To investigate the efficacy and safety of fumagillin in a real-life setting.<br><br>METHODS: As required by the French Medicine Agency, all patients receiving fumagillin were enrolled in a prospective study to evaluate its efficacy and safety. Stool examination with identification of E. bieneusi by PCR was performed at baseline, end of treatment and monthly thereafter for 6&#x2009;months. Safety was monitored up to 6&#x2009;months and full blood counts were monitored up to 42&#x2009;days after treatment initiation. The primary endpoint was safety. Parasite clearance and relapses were secondary endpoints.<br><br>RESULTS: From 2007 to 2018, 166 patients received fumagillin, including 6 children. Patients were transplant recipients (84%), HIV-infected patients (13%) or had another cause of immunosuppression (5%). Serious adverse events were reported in 41 patients (25%), mainly thrombocytopenia (15%) and neutropenia (5%), with two haemorrhagic events leading to one death. Severe thrombocytopenia (<50&#x2009;G/L) developed in 50 patients (29.6%), neutropenia (<1&#x2009;G/L) in 20 patients (11.8%) and severe anaemia (<8&#x2009;g/dL) in 21 patients (12.4%). At the end of treatment, 94% of patients with available stool examination (n&#x2009;=&#x2009;132) had no spores detected. Among 99 patients with available follow-up after the end of treatment, three parasite relapses were documented.<br><br>CONCLUSIONS: E. bieneusi microsporidiosis was mainly diagnosed in transplant recipients. Fumagillin was associated with haematological toxicity but showed high efficacy with a low relapse rate.}, }
@article {pmid33123253, year = {2020}, author = {Wang, J and Yang, HR and Wang, DJ and Wang, XX}, title = {Association between the gut microbiota and patient responses to cancer immune checkpoint inhibitors.}, journal = {Oncology letters}, volume = {20}, number = {6}, pages = {342}, pmid = {33123253}, issn = {1792-1074}, abstract = {Studies are increasingly investigating the association between the gut microbiota and the outcomes of immunotherapy in patients with cancer. Notably, certain studies have demonstrated that the gut microbiota serves a key role in regulating a patient's response to immunotherapy. In the present review, the potential associations between the gut microbiota, and cancer, host immunity and cancer immunotherapy are reviewed. Furthermore, the effects of fecal microbiota transplantation, antibiotics, probiotics, prebiotics, synbiotics, components of traditional Chinese medicine and various lifestyle factors on the gut microbiota and cancer immunotherapy outcomes are discussed. Certain dominant bacterial groups in the context of cancer immunotherapy and certain effective methods for optimizing immunotherapy by regulating the gut microbiota have been identified. Further investigation may enable the rapid conversion of these discoveries into practical products and clinically applicable methods.}, }
@article {pmid33122357, year = {2020}, author = {Guo, H and Chou, WC and Lai, Y and Liang, K and Tam, JW and Brickey, WJ and Chen, L and Montgomery, ND and Li, X and Bohannon, LM and Sung, AD and Chao, NJ and Peled, JU and Gomes, ALC and van den Brink, MRM and French, MJ and Macintyre, AN and Sempowski, GD and Tan, X and Sartor, RB and Lu, K and Ting, JPY}, title = {Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6516}, pages = {}, pmid = {33122357}, issn = {1095-9203}, support = {P40 OD010995/OD/NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; R21 AG066388/AG/NIA NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; U19 AI067798/AI/NIAID NIH HHS/United States ; R01 ES024950/ES/NIEHS NIH HHS/United States ; R35 CA232109/CA/NCI NIH HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; P01 DK094779/DK/NIDDK NIH HHS/United States ; T32 CA009156/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; UC6 AI058607/AI/NIAID NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 CA203950/CA/NCI NIH HHS/United States ; }, mesh = {Acute Radiation Syndrome/*microbiology/prevention &amp; control/therapy ; Animals ; Clostridiales/*metabolism ; Enterococcaceae/*metabolism ; Fatty Acids, Volatile/*metabolism/therapeutic use ; *Gastrointestinal Microbiome ; Humans ; Metabolomics ; Mice ; Mice, Inbred C57BL ; *Radiation Protection ; Survivors ; Tryptophan/*metabolism ; }, abstract = {Ionizing radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, and cerebrovascular injuries. We investigated a population of mice that recovered from high-dose radiation to live normal life spans. These "elite-survivors" harbored distinct gut microbiota that developed after radiation and protected against radiation-induced damage and death in both germ-free and conventionally housed recipients. Elevated abundances of members of the bacterial taxa Lachnospiraceae and Enterococcaceae were associated with postradiation restoration of hematopoiesis and gastrointestinal repair. These bacteria were also found to be more abundant in leukemia patients undergoing radiotherapy, who also displayed milder gastrointestinal dysfunction. In our study in mice, metabolomics revealed increased fecal concentrations of microbially derived propionate and tryptophan metabolites in elite-survivors. The administration of these metabolites caused long-term radioprotection, mitigation of hematopoietic and gastrointestinal syndromes, and a reduction in proinflammatory responses.}, }
@article {pmid33122176, year = {2020}, author = {Yang, Y and Li, L and Xu, C and Wang, Y and Wang, Z and Chen, M and Jiang, Z and Pan, J and Yang, C and Li, X and Song, K and Yan, J and Xie, W and Wu, X and Chen, Z and Yuan, Y and Zheng, S and Yan, J and Huang, J and Qiu, F}, title = {Cross-talk between the gut microbiota and monocyte-like macrophages mediates an inflammatory response to promote colitis-associated tumourigenesis.}, journal = {Gut}, volume = {70}, number = {8}, pages = {1495-1506}, pmid = {33122176}, issn = {1468-3288}, abstract = {OBJECTIVE: Macrophages are among the most abundant cells in the colon tumour microenvironment, and there is a close relationship among monocytes, macrophages and the gut microbiota. Alterations in the gut microbiota are involved in tumour development, but the underlying mechanisms remain unclear. We aim to elucidate the temporal changes in macrophage subsets and functions, and how these dynamics are regulated by microbial cues in the initiation of colitis-associated cancer.<br><br>DESIGN: A mouse model of colitis-associated tumourigenesis was established to determine macrophage dynamics. The role of monocyte-like macrophage (MLM) was confirmed by targeting its chemotaxis. The effects of the gut microbiota were assessed by antibiotic treatment and faecal microbiota transplantation.<br><br>RESULTS: A selective increase in MLMs was observed in the initial stages of colitis-associated cancer, with an enhanced secretion of inflammatory cytokines. MLM accumulation was regulated by CCL2 expression of colonic epithelial cells, which was influenced by bacteria-derived lipopolysaccharide (LPS). LPS further stimulated interleukin 1&#x3b2; production from MLMs, inducing interleukin-17-producing T-helper cell activation to promote inflammation. These observations were also supported by altered microbial composition associated with human colitis and colorectal cancer, evolving transcriptional signature and immune response during human colitis-associated tumourigenesis.<br><br>CONCLUSIONS: The gut microbiota uses LPS as a trigger to regulate MLM accumulation in a chemokine-dependent manner and generate a precancerous inflammatory milieu to facilitate tumourigenesis.}, }
@article {pmid33121699, year = {2020}, author = {Lee, SD}, title = {Health Maintenance in Ulcerative Colitis.}, journal = {Gastroenterology clinics of North America}, volume = {49}, number = {4}, pages = {xv-xvi}, doi = {10.1016/j.gtc.2020.09.002}, pmid = {33121699}, issn = {1558-1942}, mesh = {*Colitis, Ulcerative/diagnosis/etiology/surgery/therapy ; Fecal Microbiota Transplantation ; Female ; Humans ; Maintenance Chemotherapy ; Male ; Patient Care ; Quality of Life ; }, }
@article {pmid33121693, year = {2020}, author = {Cheng, YW and Fischer, M}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis. Are We Ready for Primetime?.}, journal = {Gastroenterology clinics of North America}, volume = {49}, number = {4}, pages = {739-752}, doi = {10.1016/j.gtc.2020.08.006}, pmid = {33121693}, issn = {1558-1942}, mesh = {Colitis, Ulcerative/*microbiology/*therapy ; Dysbiosis/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Randomized Controlled Trials as Topic ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {"Patients with inflammatory bowel disease, including ulcerative colitis (UC) and Crohn disease, have altered gut microbiomes. The success of fecal microbiota transplantation (FMT) in the treatment of Clostridioides difficile infection, a disease that is also marked by dysbiosis, has spurred research in applying FMT to UC. So far, 3 randomized controlled trials have demonstrated benefit in mild to moderate UC disease course after FMT. However, important questions regarding optimal stool preparation, route, and frequency of administration, as well as characteristics of the stool donor and recipient still remain."}, }
@article {pmid33118360, year = {2020}, author = {Silva, JC and Ponte, A and Mota, M and Pinho, R and Vieira, N and Oliveira, R and Mota-Carvalho, N and Gomes, AC and Afecto, E and Carvalho, J}, title = {Fecal microbiota transplantation in the intestinal decolonization of carbapenamase-producing enterobacteriaceae.}, journal = {Revista espanola de enfermedades digestivas}, volume = {112}, number = {12}, pages = {925-928}, doi = {10.17235/reed.2020.7150/2020}, pmid = {33118360}, issn = {1130-0108}, mesh = {*Clostridium Infections ; Enterobacteriaceae ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Intestines ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: fecal microbiota transplantation (FMT) is effective for recurrent Clostridium difficile infection (CDI). Intestinal decolonization of carbapenamase-producing enterobacteriaceae (CPE) can prevent transmission and infection by these agents. The aim of this study was to assess CPE decolonization after FMT.<br><br>METHODS: this was a case-series study that consecutively included all CPE-carriers that underwent FMT between 2014 and 2019. The indications included refractory/recurrent CDI and CPE-decolonization.<br><br>RESULTS: out of 21 CPE-carriers, eight were excluded due to incomplete post-FMT testing. CPE decolonization was confirmed in 76.9 % (n = 10). The median decolonization time was 16-weeks (IQR-23) and ranged from two to 53 weeks.<br><br>CONCLUSION: FMT may be used in the clinical practice for CPE-decolonization as an alternative to combined antibiotic regimens.}, }
@article {pmid33117731, year = {2020}, author = {Li, Q and Jin, M and Liu, Y and Jin, L}, title = {Gut Microbiota: Its Potential Roles in Pancreatic Cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {572492}, pmid = {33117731}, issn = {2235-2988}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Pancreas ; *Pancreatic Neoplasms/therapy ; *Probiotics/therapeutic use ; }, abstract = {Pancreatic cancer is considered a lethal disease with a low survival rate due to its late-stage diagnosis, few opportunities for resection and lack of effective therapeutic strategies. Multiple, highly complex effects of gut microbiota on pancreatic cancer have been recognized as potential strategies for targeting tumorigenesis, development and treatment in recent decades; some of the treatments include antibiotics, probiotics, and fecal microbiota transplantation. Several bacterial species are associated with carcinogenesis of the pancreas, while some bacterial metabolites contribute to tumor-associated low-grade inflammation and immune responses via several proinflammatory factors and signaling pathways. Given the limited evidence on the interplay between gut microbiota and pancreatic cancer, risk factors associated with pancreatic cancer, such as diabetes, chronic pancreatitis and obesity, should also be taken into consideration. In terms of treatment of pancreatic cancer, gut microbiota has exhibited multiple effects on both traditional chemotherapy and the recently successful immunotherapy. Therefore, in this review, we summarize the latest developments and advancements in gut microbiota in relation to pancreatic cancer to elucidate its potential value.}, }
@article {pmid33117435, year = {2020}, author = {Yang, XA and Lv, F and Wang, R and Chang, Y and Zhao, Y and Cui, X and Li, H and Yang, S and Li, S and Zhao, X and Mo, Z and Yang, F}, title = {Potential role of intestinal microflora in disease progression among patients with different stages of Hepatitis B.}, journal = {Gut pathogens}, volume = {12}, number = {}, pages = {50}, pmid = {33117435}, issn = {1757-4749}, abstract = {BACKGROUND: Increasing evidence demonstrate that the gut microbiota is involved in the pathogenesis of liver diseases, and faecal microbiota transplantation is considered to be a promising new treatment option. However, there are no reports on the intestinal flora of asymptomatic HBV carriers using next-generation sequencing. This study intends to investigate the potential role of the intestinal microflora in predicting the progression of Hepatitis B patients in different non-cancerous stages.<br><br>RESULTS: A total of 266 patients with different stages of Hepatitis B and 31 healthy controls were included in this study. Some of the subjects&#xa0;(217 cases) underwent 16S rRNA gene sequencing. Compared with the control group (CK), the &#x3b1; diversity of patients in Group A (HBV carrier) slightly increased, while that of patients in the other three groups decreased. Each group of patients, especially&#xa0;those in Group&#xa0;C (cirrhosis) and&#xa0;Group&#xa0;D (acute-on-chronic liver failure), could be separated from the CK using weighted&#xa0;UniFrac PCoA and ANOSIM. LEfSe revealed that&#xa0;40 taxa belonging to three&#xa0;phyla had an LDA larger than 4. In&#xa0;addition to the comparison between Group B (chronic Hepatitis B) and&#xa0;Group C,&#xa0;the specific flora and potential taxonomic function were also identified. Different microbial communities were found to be&#xa0;highly&#xa0;correlated&#xa0;with clinical indicators and the Child-Pugh&#xa0;scores. Changes in the microbial community were highly related to the alternations of host metabolism, which in turn, was related to the development of Hepatitis B. Our analysis identified a total of 47 strains with potential biomarker functions at all levels except&#xa0;for the phylum level.<br><br>CONCLUSIONS: Faecal microbiota transplantation of some potential beneficial bacteria can change with the occurrence of disease, and HBV carriers might be the most suitable donors.}, }
@article {pmid33117316, year = {2020}, author = {Dai, X and Hou, H and Zhang, W and Liu, T and Li, Y and Wang, S and Wang, B and Cao, H}, title = {Microbial Metabolites: Critical Regulators in NAFLD.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {567654}, pmid = {33117316}, issn = {1664-302X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease throughout the world. The relationship between gut microbiota and NAFLD has been extensively investigated. The gut microbiota is involved in the regulation of NAFLD by participating in the fermentation of indigestible food, interacting with the intestinal mucosal immune system, and influencing the intestinal barrier function, leading to signaling alteration. Meanwhile, the microbial metabolites not only affect the signal transduction pathway in the gut but also reach the liver far away from gut. In this review, we focus on the effects of certain key microbial metabolites such as short-chain fatty acids, trimethylamine-N-oxide, bile acids, and endogenous ethanol and indole in NAFLD, and also summarize several potential therapies targeting the gut-liver axis and modulation of gut microbiota metabolites including antibiotics, prebiotics, probiotics, bile acid regulation, and fecal microbiota transplantation. Understanding the complex interactions between microbial metabolites and NAFLD may provide crucial insight into the pathogenesis and treatment of NAFLD.}, }
@article {pmid33116952, year = {2020}, author = {Kullar, R and Tran, MN and Goldstein, EJC}, title = {Investigational Treatment Agents for Recurrent Clostridioides difficile Infection (rCDI).}, journal = {Journal of experimental pharmacology}, volume = {12}, number = {}, pages = {371-384}, pmid = {33116952}, issn = {1179-1454}, abstract = {Clostridioides difficile infection (CDI) is a major cause of nosocomial diarrhea that is deemed a global health threat. C. difficile strain BI/NAP1/027 has contributed to the increase in the mortality, severity of CDI outbreaks and recurrence rates (rCDI). Updated CDI treatment guidelines suggest vancomycin and fidaxomicin as initial first-line therapies that have initial clinical cure rates of over 80%. Unacceptably high recurrence rates of 15-30% in patients for the first episode and 40% for the second recurrent episode are reported. Alternative treatments for rCDI include fecal microbiota transplant and a human monoclonal antibody, bezlotoxumab, that can be used in patients with high risk of rCDI. Various emerging potential therapies with narrow spectrum of activity and little systemic absorption that are in development include 1) Ibezapolstat (formerly ACX-362E), MGB-BP-3, and DS-2969b-targeting bacterial DNA replication, 2) CRS3213 (REP3123)-inhibiting toxin production and spore formation, 3) ramizol and ramoplanin-affecting bacterial cell wall, 4) LFF-571-blocking protein synthesis, 5) Alanyl-L-Glutamine (alanylglutamine)-inhibiting damage caused by C. difficile by protecting intestinal mucosa, and 6) DNV3837 (MCB3681)-prodrug consisting of an oxazolidinone-quinolone combination that converts to the active form DNV3681 that has activity in vitro against C. difficile. This review article provides an overview of these developing drugs that can have potential role in the treatment of rCDI and in lowering recurrence rates.}, }
@article {pmid33116044, year = {2021}, author = {Han, Y and Wu, L and Ling, Q and Wu, P and Zhang, C and Jia, L and Weng, H and Wang, B}, title = {Intestinal Dysbiosis Correlates With Sirolimus-induced Metabolic Disorders in Mice.}, journal = {Transplantation}, volume = {105}, number = {5}, pages = {1017-1029}, doi = {10.1097/TP.0000000000003494}, pmid = {33116044}, issn = {1534-6080}, mesh = {Animals ; Bacteria/growth &amp; development/*metabolism ; Cytokines/metabolism ; Disease Models, Animal ; Dysbiosis ; Dyslipidemias/chemically induced/metabolism/*microbiology/prevention &amp; control ; Feces/microbiology ; *Gastrointestinal Microbiome ; Inflammation Mediators/metabolism ; *Insulin Resistance ; Intestinal Mucosa/metabolism/*microbiology ; Lacticaseibacillus rhamnosus/growth &amp; development/metabolism ; Male ; Metabolic Syndrome/chemically induced/metabolism/*microbiology/prevention &amp; control ; Mice, Inbred C57BL ; Probiotics ; *Sirolimus ; Mice ; }, abstract = {BACKGROUND: Long-time use of pharmacological immunosuppressive agents frequently leads to metabolic disorders. Most studies have focused on islet toxicity leading to posttransplantation diabetes mellitus. In contrast, the link between intestinal dysbiosis and immunosuppressive drug-induced metabolic disorders remains unclear.<br><br>METHODS: We established a mouse model of metabolic abnormality via sirolimus treatment. Fecal microbiota was examined using 16S rRNA gene MiSeq sequencing. Intestinal barrier function was assessed using fluorescein isothiocyanate-dextran assay and mucus immunostaining. Systemic inflammation was determined using a multiplexed fluorescent bead-based immunoassay.<br><br>RESULTS: Sirolimus induced dyslipidemia and glucose intolerance in mice in a dose-dependent manner. Interestingly, the clinical-mimicking dose of sirolimus altered the intestinal microbiota community, which was characterized by the enrichment of Proteobacteria, depletion of Akkermansia, and potential function shifts to those involved in lipid metabolism and the immune system. In addition, the clinical-mimicking dose of sirolimus reduced the thickness of the intestinal mucosal layer, increased the intestinal permeability, and enriched the circulating pro-inflammatory factors, including interleukin (IL)-12, IL-6, monocyte chemotactic protein 1, granulocyte-macrophage colony stimulating factor, and IL-1&#x3b2;. Our results showed a close association between intestinal dysbiosis, intestinal barrier failure, systemic inflammation, and metabolic disorders. Furthermore, we demonstrated that oral intervention in the gut microbiota by Lactobacillus rhamnosus HN001 protected against intestinal dysbiosis, especially by depleting the lipopolysaccharide-producing Proteobacteria, and attenuated the sirolimus-induced systemic inflammation, dyslipidemia, and insulin resistance.<br><br>CONCLUSIONS: Our study demonstrated a potentially causative role of intestinal dysbiosis in sirolimus-induced metabolic disorders, which will provide a novel therapeutic target for transplant recipients.}, }
@article {pmid33111793, year = {2020}, author = {Luz, MRMPD and Waizbort, RF}, title = {[Fecal microbiota transplants in the treatment of pseudomembranous colitis (1958-2013): priority of discovery and thought styles in the academic literature].}, journal = {Historia, ciencias, saude--Manguinhos}, volume = {27}, number = {3}, pages = {859-878}, doi = {10.1590/S0104-59702020000400009}, pmid = {33111793}, issn = {1678-4758}, mesh = {Enterocolitis, Pseudomembranous/*history/microbiology/therapy ; Fecal Microbiota Transplantation/*history ; Gastrointestinal Microbiome ; Historiography ; History, 20th Century ; History, 21st Century ; Humans ; }, abstract = {In 1958, Eiseman and contributors published the first scientific paper reporting the use of fecal microbiota transplant for treating pseudomembranous colitis. The relevance of this innovative paper was only acknowledged in 1990. The academic literature on the theme is characterized by a narrative that has undergone successive revisions. We suggest that such revisions were based on claims of priority of scientific discoveries, as described by Merton. The revival of fecal microbiota transplants is interpreted as a process of genesis of a scientific fact, as defined by Fleck: there is a switch from a thought style based on the use of antibiotics to treat infectious diseases to another that accepts the ecological relations between hosts, vectors and parasites.}, }
@article {pmid33110112, year = {2020}, author = {Kazemian, N and Ramezankhani, M and Sehgal, A and Khalid, FM and Kalkhoran, AHZ and Narayan, A and Wong, GK and Kao, D and Pakpour, S}, title = {The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {18349}, pmid = {33110112}, issn = {2045-2322}, mesh = {Adult ; Bacteroidetes/metabolism ; Clostridiales/metabolism ; Clostridioides/metabolism ; Clostridium Infections/microbiology/therapy ; Desulfovibrio/metabolism ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Humans ; Machine Learning ; Male ; Metagenomics ; Tissue Donors ; Treatment Outcome ; }, abstract = {Fundamental restoration ecology and community ecology theories can help us better understand the underlying mechanisms of fecal microbiota transplantation (FMT) and to better design future microbial therapeutics for recurrent Clostridioides difficile infections (rCDI) and other dysbiosis-related conditions. In this study, stool samples were collected from donors and rCDI patients one week prior to FMT (pre-FMT), as well as from patients one week following FMT (post-FMT). Using metagenomic sequencing and machine learning, our results suggested that FMT outcome is not only dependent on the ecological structure of the recipients, but also the interactions between the donor and recipient microbiomes at the taxonomical and functional levels. We observed that the presence of specific bacteria in donors (Clostridioides spp., Desulfovibrio spp., Odoribacter spp. and Oscillibacter spp.) and the absence of fungi (Yarrowia spp.) and bacteria (Wigglesworthia spp.) in recipients prior to FMT could predict FMT success. Our results also suggested a series of interlocked mechanisms for FMT success, including the repair of the disturbed gut ecosystem by transient colonization of nexus species followed by secondary succession of bile acid metabolizers, sporulators, and short chain fatty acid producers.}, }
@article {pmid33106983, year = {2021}, author = {Dembrovszky, F and Gede, N and Szakács, Z and Hegyi, P and Kiss, S and Farkas, N and Molnár, Z and Imrei, M and Dohos, D and Péterfi, Z}, title = {Fecal Microbiota Transplantation May Be the Best Option in Treating Multiple Clostridioides difficile Infection: A Network Meta-Analysis.}, journal = {Infectious diseases and therapy}, volume = {10}, number = {1}, pages = {201-211}, pmid = {33106983}, issn = {2193-8229}, support = {GINOP-2.3.2-15-2016-00048//European Regional Development Fund/ ; EFOP-3.6.2-16-2017-00006//European Regional Development Fund/ ; }, abstract = {INTRODUCTION: Clostridioides difficile (formerly Clostridium) infection (CDI) is the most common cause of healthcare-associated diarrhea with high mortality and recurrence rate; furthermore, the treatment of recurrent cases is a challenge. In this network meta-analysis, we aimed to compare all available therapies against multiple recurrent CDI (mrCDI) and rank them by efficacy.<br><br>METHODS: After a systematic search, randomized controlled trials (RCT) with any interventions against mrCDI were included. Data were extracted to the study database using Excel. Risk of bias assessment was performed with the Cochrane RoB&#xa0;2 tool. The primary outcome was the clinical cure of CDI and the secondary outcome was the recurrence of CDI. A Bayesian method was performed to investigate the efficacy rank order of therapies. We registered our protocol with the Prospero Center for Reviews and Dissemination (registration no. CRD42020160365).<br><br>RESULTS: Six RCTs with seven interventions were included in the quantitative synthesis. According to the surface under the cumulative ranking curve values, fecal microbiota transplantation (FMT) after a short course of vancomycin therapy (83%) shows the highest efficacy for clinical cure. Tolevamer and vancomycin&#x2009;+&#x2009;FMT seemed to be the most effective in preventing recurrence (87% and 75%, respectively).<br><br>CONCLUSION: Vancomycin&#x2009;+&#x2009;FMT is perhaps the most effective option for the treatment and prevention of mrCDI, while tolevamer is also effective in preventing recurrence.}, }
@article {pmid33106354, year = {2021}, author = {de Groot, P and Nikolic, T and Pellegrini, S and Sordi, V and Imangaliyev, S and Rampanelli, E and Hanssen, N and Attaye, I and Bakker, G and Duinkerken, G and Joosten, A and Prodan, A and Levin, E and Levels, H and Potter van Loon, B and van Bon, A and Brouwer, C and van Dam, S and Simsek, S and van Raalte, D and Stam, F and Gerdes, V and Hoogma, R and Diekman, M and Gerding, M and Rustemeijer, C and de Bakker, B and Hoekstra, J and Zwinderman, A and Bergman, J and Holleman, F and Piemonti, L and De Vos, W and Roep, B and Nieuwdorp, M}, title = {Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial.}, journal = {Gut}, volume = {70}, number = {1}, pages = {92-105}, pmid = {33106354}, issn = {1468-3288}, mesh = {Adolescent ; Adult ; C-Peptide/metabolism ; Diabetes Mellitus, Type 1/metabolism/microbiology/*prevention &amp; control ; Duodenum/metabolism/microbiology ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome ; Humans ; Insulin-Secreting Cells/physiology ; Male ; Transplantation, Autologous ; Young Adult ; }, abstract = {OBJECTIVE: Type 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota-immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT).<br><br>DESIGN: Patients with recent-onset (<6 weeks) T1D (18-30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition.<br><br>RESULTS: Stimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=-0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics.<br><br>CONCLUSION: FMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D.<br><br>TRIAL REGISTRATION NUMBER: NTR3697.}, }
@article {pmid33104419, year = {2020}, author = {Alexander, JL and Mullish, BH}, title = {A Guide to the Gut Microbiome and its Relevance to Critical Care.}, journal = {British journal of nursing (Mark Allen Publishing)}, volume = {29}, number = {19}, pages = {1106-1112}, doi = {10.12968/bjon.2020.29.19.1106}, pmid = {33104419}, issn = {2052-2819}, mesh = {Critical Care ; *Gastroenteritis ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases ; *Probiotics ; }, abstract = {Although it is well-established that particular bacteria may cause gastroenteritis and other infections when present in the gut, it is only recently that scientists have made significant inroads into understanding the huge number of other bacteria and additional microbes that live within the gastrointestinal tract, referred to as the gut microbiome. In particular, it is now recognised that bacteria within the gut microbiome have a wide variety of roles in maintaining different aspects of human health, and that disturbances of these bacteria may potentially cause or contribute to a number of different medical conditions, including particular infections, certain cancers, and chronic conditions, including inflammatory bowel disease. Moreover, there is increasing awareness that these bacteria help determine how the body responds to medication, including antibiotics and chemotherapy. There has been growing interest in different approaches to alter the gut microbiome as a novel approach to medical therapy. This article provides an overview of the importance of the gut microbiome, with a particular focus on critical care.}, }
@article {pmid33102769, year = {2020}, author = {Gill, M and Blacketer, C and Chitti, F and Telfer, K and Papanicolas, L and Dann, LM and Tucker, EC and Bryant, RV and Costello, SP}, title = {Physician and patient perceptions of fecal microbiota transplant for recurrent or refractory Clostridioides difficile in the first 6 years of a central stool bank.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {4}, number = {5}, pages = {950-957}, pmid = {33102769}, issn = {2397-9070}, abstract = {BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent or refractory Clostridioides difficile infection (rCDI). Despite inclusion in society guidelines, the uptake of FMT therapy has been variable. Physician and patient attitudes may be a barrier to evidence-based uptake of therapies; however, data assessing attitudes regarding FMT for rCDI are limited.<br><br>METHODS: The South Australian FMT for CDI database prospectively recorded patient outcomes of FMT for CDI from August 2013 to January 2019. A total of 93 consecutive patients who underwent FMT for rCDI in South Australia were invited to participate in a 20-question survey regarding the patient experience of FMT. All gastroenterologists and infectious disease physicians practicing in South Australia were invited to participate in an online survey comprised of 22 questions that addressed referral experience, indications for referral, perceived risks, and regulation and funding.<br><br>RESULTS: Fifty-four patients (54/93, 58%) returned the survey, of whom 52 (96%) would recommend FMT to others, and 51 (94%) were satisfied with treatment outcome. Fifty physicians returned the online survey (50/100, 50%), of whom 23 (46%) were concerned about disease transmission risk, and 15 (30%) believed that the risk of FMT would outweigh the benefit. Infectious diseases physicians and advanced trainees had significantly greater concern regarding the potential alteration of the microbiome than gastroenterology physicians and advanced trainees (8/17 (47%) vs 6/33 (18%); P = 0.047).<br><br>CONCLUSION: Despite high levels of patient-reported satisfaction following FMT, physician-reported reservations exist and may present a barrier to uptake of this therapy.}, }
@article {pmid33102555, year = {2020}, author = {Rossi, G and Pengo, G and Galosi, L and Berardi, S and Tambella, AM and Attili, AR and Gavazza, A and Cerquetella, M and Jergens, AE and Guard, BC and Lidbury, JA and Stainer, JM and Crovace, AM and Suchodolski, JS}, title = {Effects of the Probiotic Mixture Slab51® (SivoMixx®) as Food Supplement in Healthy Dogs: Evaluation of Fecal Microbiota, Clinical Parameters and Immune Function.}, journal = {Frontiers in veterinary science}, volume = {7}, number = {}, pages = {613}, pmid = {33102555}, issn = {2297-1769}, abstract = {The gut microbiota plays a crucial role in several physiologic functions of the host. In humans and animals, manipulation of the intestinal microbiota by oral administration of probiotic lactic acid bacteria plays a significant role in modulating the immune system. The aim of this study was to evaluate the safety of the probiotic mixture Slab51® and the capacity of this mixture to stimulate immune function in healthy dogs. Twenty dogs were divided in two groups and received a control diet or the same diet supplemented with a dose of 400 billion cfu of lyophilized bacteria for a period of 60 days. Body weight, food intake, body condition score (BCS), fecal score (FSS), fecal immunoglobulin IgA concentration, plasma IgG concentration, and fecal microbiota composition were monitored. Weight, food intake, BCS, FSS, and biochemical parameters remained unchanged during the treatment in both groups of animals. The fecal microbiota showed a significant decrease in the abundance of Clostridium perfringens and a significant increase in the abundance of beneficial Bifidobacterium and Lactobacillus organisms (p < 0.05). Fecal IgA and plasma IgG levels were significantly higher in the group receiving the probiotic compared to healthy controls. These data show that dietary supplementation with the probiotic mixture Slab51® is safe and well-tolerated, modulating the composition of the intestinal microbiota, and enhancing specific immune functions in healthy dogs.}, }
@article {pmid33102406, year = {2020}, author = {Koo, H and Crossman, DK and Morrow, CD}, title = {Strain Tracking to Identify Individualized Patterns of Microbial Strain Stability in the Developing Infant Gut Ecosystem.}, journal = {Frontiers in pediatrics}, volume = {8}, number = {}, pages = {549844}, pmid = {33102406}, issn = {2296-2360}, abstract = {Stable microbe and host interactions are established during the development of the infant gut microbial community that provide essential functions for the efficient digestion of food, immune development, and resistance to colonization with pathogens. To further delineate the stability of the gut microbial community during this time, we have used microbial strain tracking analysis with published longitudinal metagenomic data sets to identify strains that persist in the developing infant gut ecosystem. In the first study, 17 infants were evaluated that had not received antibiotics for 3 years after birth. An infant specific pattern was seen for stable and unstable microbial strains during this time, with only one infant having no stable strains identified out of available strains during the first 3 years. Strain tracking was also applied to follow microbes in a separate set of 14 infants that had multiple doses of antibiotics over the 3 years. In 10 out of 14 infants given multiple antibiotics during the first 3 years, we identified a unique pattern of transient strains that appeared after multiple antibiotic treatments for a short time compared to that in infants not on antibiotics. In a second, independent study, we selected a subset of 9 infants from a previously published study consisting of high-density longitudinal fecal sampling to analyze the gut microbial strain stability of Bacteroides vulgatus and Bifidobacterium adolescentis for up to 6 years following birth. Individual specific patterns were found consisting of varying dominant microbial strains that were independent of antibiotic exposure and birth mode. Our analysis demonstrates an individual specific inherent variability of extinction and persistence of microbial strains in the infant gut community during a time of development that is critical for interactions necessary for establishing normal metabolism and the development of the host immune response.}, }
@article {pmid33098239, year = {2020}, author = {Li, W and Chen, C and Chen, M and Zhang, X and Ji, Q and Wang, Y and Zheng, Q and Tan, S and Gao, X and Lu, Y}, title = {Salted and Unsalted Zhàcài (Brassica juncea var. tumida) Alleviated High-Fat Diet-Induced Dyslipidemia by Regulating Gut Microbiota: A Multiomics Study.}, journal = {Molecular nutrition &amp; food research}, volume = {}, number = {}, pages = {e2000798}, doi = {10.1002/mnfr.202000798}, pmid = {33098239}, issn = {1613-4133}, abstract = {SCOPE: Zhàcài (ZC), a salting-processed Brassica juncea var. tumida vegetable, is widely consumed as a pickle, but little is known about the health benefits of both salted and unsalted ZC as a whole food.<br><br>METHODS AND RESULTS: The preventive effects of salted and unsalted ZC against dyslipidemia are assessed in high-fat (HF) diet-fed mice. HF intake for 12 continuous weeks cause dyslipidemia in mice, as evidenced by the elevations in serum total triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels by 30%, 66%, and 117%, respectively. Metabolomics analysis and the 16S rRNA genes sequencing suggest that dietary administration of salted and unsalted ZC (2.5% w/w) alleviates HF-induced dyslipidemia, metabolic disorders of short-chain fatty acids, and disturbance of intestinal flora in mice. These positive effects of unsalted ZC are stronger than those of salted ZC. Moreover, fecal bacteria transplantation confirms the antidyslipidemia of ZC.<br><br>CONCLUSION: These results suggest that consumption of ZC may prevent HF-induced dyslipidemia by regulating gut microbiota.}, }
@article {pmid33096925, year = {2020}, author = {Losurdo, G and Giorgio, F and Pricci, M and Girardi, B and Russo, F and Riezzo, G and Martulli, M and Piazzolla, M and Cocomazzi, F and Abbruzzi, F and Parente, E and Paolillo, R and Mileti, A and Iannone, A and Principi, M and Ierardi, E and Leo, AD}, title = {Helicobacter pylori Primary and Secondary Genotypic Resistance to Clarithromycin and Levofloxacin Detection in Stools: A 4-Year Scenario in Southern Italy.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {33096925}, issn = {2079-6382}, abstract = {Antibiotic resistance has become an emerging problem for treating Helicobacter pylori (H. pylori) infection. Clarithromycin and levofloxacin are two key antibiotics used for its eradication. Therefore, we reviewed our experience with genotypic resistance analysis in stools to both clarithromycin and levofloxacin in the last four years to evaluate time trends, both in naive and failure patients. Patients collected a fecal sample using the THD fecal test device. Real-time polymerase chain reaction was performed to detect point mutations conferring resistance to clarithromycin (A2142C, A2142G, and A2143G in 23S rRNA) and levofloxacin (substitutions at amino acid position 87 and 91 of gyrA). One hundred and thirty-five naive patients were recruited between 2017-2020. Clarithromycin resistance was detected in 37 (27.4%). The time trend did not show any significant variation from 2017 to 2020 (p = 0.33). Primary levofloxacin resistance was found in 26 subjects (19.2%), and we observed a dramatic increase in rates from 2017 (10%) to 2018 (3.3%), 2019 (20%), and 2020 (37.8%). Ninety-one patients with at least one eradication failure were recruited. Secondary resistance to clarithromycin and levofloxacin was found in 59 (64.8%) and 45 patients (59.3%), respectively. In conclusion, our geographic area has a high risk of resistance to clarithromycin. There is also a progressive spreading of levofloxacin-resistant strains.}, }
@article {pmid33094595, year = {2020}, author = {Poortmans, P and Kindt, S}, title = {Diagnostic approach to chronic diarrhoea and recent insights in treatment of functional diarrhoea including irritable bowel syndrome.}, journal = {Acta gastro-enterologica Belgica}, volume = {83}, number = {3}, pages = {461-474}, pmid = {33094595}, issn = {1784-3227}, mesh = {Bile Acids and Salts ; *Diarrhea/diagnosis/etiology/therapy ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome/diagnosis/therapy ; Parasympatholytics ; }, abstract = {Chronic diarrhoea is a common clinical problem with a plethora of possible causes and underlying pathophysiological mechanisms. The value of diagnostic assessment by laboratory testing, stool analysis, evaluation of bile acid malabsorption, endoscopy, breath testing and radiological imaging techniques is discussed. The decision to focus investigations on excluding certain pathologies remains a matter of clinical judgement. Functional diarrhoea and irritable bowel syndrome (IBS) being the most frequent causes of chronic diarrhoea, recent insights in the role of dietary management, management of dysbiosis by pre-, pro- and antibiotics and faecal microbiota transplantation, as well as targeted treatment by spasmolytics, 5-HT3 receptor antagonists and eluxadoline will be reviewed.}, }
@article {pmid33091412, year = {2021}, author = {Nieuwdorp, M and Madsen, K}, title = {The Promise of Maintaining Diet-Induced Weight Loss by Swallowing One's Own Feces: Time to Provide a Do-It-Yourself Manual?.}, journal = {Gastroenterology}, volume = {160}, number = {1}, pages = {17-19}, doi = {10.1053/j.gastro.2020.10.025}, pmid = {33091412}, issn = {1528-0012}, mesh = {*Deglutition ; Diet ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Weight Gain ; Weight Loss ; }, }
@article {pmid33091322, year = {2021}, author = {Tashiro, H and Shore, SA}, title = {The Gut Microbiome and Ozone-induced Airway Hyperresponsiveness. Mechanisms and Therapeutic Prospects.}, journal = {American journal of respiratory cell and molecular biology}, volume = {64}, number = {3}, pages = {283-291}, doi = {10.1165/rcmb.2020-0288TR}, pmid = {33091322}, issn = {1535-4989}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Diet ; *Gastrointestinal Microbiome/drug effects ; Humans ; Lung/pathology ; Ozone/*adverse effects ; Respiratory Hypersensitivity/*chemically induced/drug therapy/*microbiology ; }, abstract = {In recent years, several new asthma therapeutics have been developed. Although many of these agents show promise in treating allergic asthma, they are less effective against nonallergic forms of asthma. The gut microbiome has important roles in human health and disease, and a growing body of evidence indicates a link between the gut microbiome and asthma. Here, we review those data focusing on the role of the microbiome in mouse models of nonallergic asthma including obese asthma and asthma triggered by exposure to air pollutants. We describe the impact of antibiotics, diet, and early life events on airway responses to the air pollutant ozone, including in the setting of obesity. We also review potential mechanisms responsible for gut-lung interactions focusing on bacterial-derived metabolites, the immune system, and hormones. Finally, we discuss future prospects for gut microbiome-targeted therapies such as fecal microbiome transplantation, prebiotics, probiotics, and prudent use of antibiotics. Better understanding of the role of the microbiome in airway responses may lead to exploration of new microbiome-targeted therapies to control asthma, especially nonallergic forms of asthma.}, }
@article {pmid33087514, year = {2020}, author = {Kang, DW and Adams, JB and Vargason, T and Santiago, M and Hahn, J and Krajmalnik-Brown, R}, title = {Distinct Fecal and Plasma Metabolites in Children with Autism Spectrum Disorders and Their Modulation after Microbiota Transfer Therapy.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {33087514}, issn = {2379-5042}, mesh = {Autism Spectrum Disorder/*metabolism/*therapy ; Child ; Chromatography, Liquid ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/*chemistry ; Gastrointestinal Microbiome ; Humans ; Metabolome ; Plasma/*chemistry ; United States ; }, abstract = {Accumulating evidence has strengthened a link between dysbiotic gut microbiota and autism. Fecal microbiota transplant (FMT) is a promising therapy to repair dysbiotic gut microbiota. We previously performed intensive FMT called microbiota transfer therapy (MTT) for children with autism spectrum disorders (ASD) and observed a substantial improvement of gastrointestinal and behavioral symptoms. We also reported modulation of the gut microbiome toward a healthy one. In this study, we report comprehensive metabolite profiles from plasma and fecal samples of the children who participated in the MTT trial. With 619 plasma metabolites detected, we found that the autism group had distinctive metabolic profiles at baseline. Eight metabolites (nicotinamide riboside, IMP, iminodiacetate, methylsuccinate, galactonate, valylglycine, sarcosine, and leucylglycine) were significantly lower in the ASD group at baseline, while caprylate and heptanoate were significantly higher in the ASD group. MTT drove global shifts in plasma profiles across various metabolic features, including nicotinate/nicotinamide and purine metabolism. In contrast, for 669 fecal metabolites detected, when correcting for multiple hypotheses, no metabolite was significantly different at baseline. Although not statistically significant, p-cresol sulfate was relatively higher in the ASD group at baseline, and after MTT, the levels decreased and were similar to levels in typically developing (TD) controls. p-Cresol sulfate levels were inversely correlated with Desulfovibrio, suggesting a potential role of Desulfovibrio on p-cresol sulfate modulation. Further studies of metabolites in a larger ASD cohort, before and after MTT, are warranted, as well as clinical trials of other therapies to address the metabolic changes which MTT was not able to correct.IMPORTANCE Despite the prevalence of autism and its extensive impact on our society, no U.S. Food and Drug Administration-approved treatment is available for this complex neurobiological disorder. Based on mounting evidences that support a link between autism and the gut microbiome, we previously performed a pioneering open-label clinical trial using intensive fecal microbiota transplant. The therapy significantly improved gastrointestinal and behavioral symptoms. Comprehensive metabolomic measurements in this study showed that children with autism spectrum disorder (ASD) had different levels of many plasma metabolites at baseline compared to those in typically developing children. Microbiota transfer therapy (MTT) had a systemic effect, resulting in substantial changes in plasma metabolites, driving a number of metabolites to be more similar to those from typically developing children. Our results provide evidence that changes in metabolites are one mechanism of the gut-brain connection mediated by the gut microbiota and offer plausible clinical evidence for a promising autism treatment and biomarkers.}, }
@article {pmid33087489, year = {2021}, author = {Zhang, SY and Li, RJW and Lim, YM and Batchuluun, B and Liu, H and Waise, TMZ and Lam, TKT}, title = {FXR in the dorsal vagal complex is sufficient and necessary for upper small intestinal microbiome-mediated changes of TCDCA to alter insulin action in rats.}, journal = {Gut}, volume = {70}, number = {9}, pages = {1675-1683}, doi = {10.1136/gutjnl-2020-321757}, pmid = {33087489}, issn = {1468-3288}, support = {FDN-143204//CIHR/Canada ; }, mesh = {Animals ; Brain/metabolism ; Brain Chemistry ; Brain Stem/metabolism/*physiology ; Diet, High-Fat ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Gene Knockdown Techniques ; Glucose Clamp Technique ; *Insulin Resistance/physiology ; Intestine, Small/metabolism/*microbiology ; Rats ; Receptors, Cytoplasmic and Nuclear/analysis/*metabolism ; Taurochenodeoxycholic Acid/analysis/*metabolism ; }, abstract = {OBJECTIVE: Conjugated bile acids are metabolised by upper small intestinal microbiota, and serum levels of taurine-conjugated bile acids are elevated and correlated with insulin resistance in people with type 2 diabetes. However, whether changes in taurine-conjugated bile acids are necessary for small intestinal microbiome to alter insulin action remain unknown.<br><br>DESIGN: We evaluated circulating and specifically brain insulin action using the pancreatic-euglycaemic clamps in high-fat (HF) versus chow fed rats with or without upper small intestinal healthy microbiome transplant. Chemical and molecular gain/loss-of-function experiments targeting specific taurine-conjugated bile acid-induced changes of farnesoid X receptor (FXR) in the brain were performed in parallel.<br><br>RESULTS: We found that short-term HF feeding increased the levels of taurochenodeoxycholic acid (TCDCA, an FXR ligand) in the upper small intestine, ileum, plasma and dorsal vagal complex (DVC) of the brain. Transplantation of upper small intestinal healthy microbiome into the upper small intestine of HF rats not only reversed the rise of TCDCA in all reported tissues but also enhanced the ability of either circulating hyperinsulinaemia or DVC insulin action to lower glucose production. Further, DVC infusion of TCDCA or FXR agonist negated the enhancement of insulin action, while genetic knockdown or chemical inhibition of FXR in the DVC of HF rats reversed insulin resistance.<br><br>CONCLUSION: Our findings indicate that FXR in the DVC is sufficient and necessary for upper small intestinal microbiome-mediated changes of TCDCA to alter insulin action in rats, and highlight a previously unappreciated TCDCA-FXR axis linking gut microbiome and host insulin action.}, }
@article {pmid33085984, year = {2020}, author = {Craven, LJ and McIlroy, JR and Mullish, BH and Marchesi, JR}, title = {Letter: intestinal microbiota transfer-updating the nomenclature to increase acceptability.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {10}, pages = {1622-1623}, doi = {10.1111/apt.16109}, pmid = {33085984}, issn = {1365-2036}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid33084400, year = {2020}, author = {Wu, P and Zhang, R and Luo, M and Zhang, T and Pan, L and Xu, S and Pan, L and Ren, F and Ji, C and Hu, R and Noureddin, M and Pandol, SJ and Han, YP}, title = {Liver Injury Impaired 25-Hydroxylation of Vitamin D Suppresses Intestinal Paneth Cell defensins, leading to Gut Dysbiosis and Liver Fibrogenesis.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {319}, number = {6}, pages = {G685-95}, pmid = {33084400}, issn = {1522-1547}, support = {P01CA163200//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; P01 DK098108/DK/NIDDK NIH HHS/United States ; 31771288//National Natural Science Foundation of China (NSFC)/ ; P01 CA163200/CA/NCI NIH HHS/United States ; P01DK098108//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; R01DA042632//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; 31571165//National Natural Science Foundation of China (NSFC)/ ; R01 DA042632/DA/NIDA NIH HHS/United States ; U01 DK108314/DK/NIDDK NIH HHS/United States ; }, abstract = {Vitamin D deficiency is co-prevalent with various liver diseases including cirrhosis, while the underlying mechanism remains elusive. Vitamin D receptor (VDR) is abundantly expressed in the distal region of small intestine, where the Paneth cells are enriched, suggesting that vitamin D signaling may modulates the intestinal Paneth cells and their production of defensins to restrain microbiome growth in the small intestine. In this study we found that in carbon tetrachloride-induced liver injury, hepatic 25-hydroxylation of vitamin D was impaired, leading to down regulated expression of Paneth cell fensins in the small intestine, gut dysbiosis, and endotoxinemia. While intraperitoneal injection of endotoxin (lipopolysaccharides) alone did not elicit liver fibrosis, it exacerbated the carbon tetrachloride initiated liver fibrogenesis. Oral gavage of synthetic Paneth cell alpha-defensin 5 (DEFA5) restored the homeostasis of gut microbiota, reduced endotoxemia, relieved liver inflammation, and ameliorated liver fibrosis. Likewise, Cholestyramine, cationic resin that can sequestrate endotoxin in the intestine, attenuated the liver fibrosis as well. Fecal transplant of the microbes derived from the DEFA5-treated donors improved liver fibrosis in the recipient mice. The intestinal Vdrconditional knockout mice exhibited reduction of Paneth cell defensins and lysozyme production, and worsened liver injury and fibrogenesis. Thus, liver injury impairs synthesis of 25(OH)VD3, which consequently impedes the Paneth cells functions in the small intestine, leading to gut dysbiosis for liver fibrogenesis.}, }
@article {pmid33082711, year = {2020}, author = {Bian, S and Wan, H and Liao, X and Wang, W}, title = {Inhibitory Effects of Apigenin on Tumor Carcinogenesis by Altering the Gut Microbiota.}, journal = {Mediators of inflammation}, volume = {2020}, number = {}, pages = {7141970}, pmid = {33082711}, issn = {1466-1861}, mesh = {Animals ; Apigenin/*pharmacology/*therapeutic use ; Azoxymethane/pharmacology ; Carcinogenesis/drug effects/metabolism ; Dextran Sulfate/pharmacology ; Disease Models, Animal ; Female ; Gastrointestinal Microbiome/*drug effects ; Mice ; Mice, Inbred BALB C ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The flavonoid apigenin is common to many plants. Although the responsible mechanisms have yet to be elucidated, apigenin demonstrates tumor suppression in vitro and in vivo. This study uses an azoxymethane (AOM)/dextran sodium sulfate- (DSS-) induced colon cancer mouse model to investigate apigenin's potential mechanism of action exerted through its effects upon gut microbiota. The size and quantity of tumors were reduced significantly in the apigenin treatment group. Using 16S rRNA high-throughput sequencing of fecal samples, the composition of gut microbiota was significantly affected by apigenin. Further experiments in which gut microbiota were reduced and feces were transplanted provided further evidence of apigenin-modulated gut microbiota exerting antitumor effects. Apigenin was unable to reduce the number or size of tumors when gut microbiota were depleted. Moreover, tumor inhibition effects were initiated following the transplant of feces from mice treated with apigenin. Our findings suggest that the effect of apigenin on the composition of gut microbiota can suppress tumors.}, }
@article {pmid33081767, year = {2020}, author = {Uzan-Yulzari, A and Morr, M and Tareef-Nabwani, H and Ziv, O and Magid-Neriya, D and Armoni, R and Muller, E and Leibovici, A and Borenstein, E and Louzoun, Y and Shai, A and Koren, O}, title = {The intestinal microbiome, weight, and metabolic changes in women treated by adjuvant chemotherapy for breast and gynecological malignancies.}, journal = {BMC medicine}, volume = {18}, number = {1}, pages = {281}, pmid = {33081767}, issn = {1741-7015}, mesh = {Adolescent ; Adult ; Aged ; Animals ; Breast Neoplasms/*complications/drug therapy ; Chemotherapy, Adjuvant/*adverse effects ; Cohort Studies ; Female ; Gastrointestinal Microbiome/*genetics ; Genital Neoplasms, Female/*complications/drug therapy ; Humans ; Mice ; Middle Aged ; Weight Gain/*drug effects ; Young Adult ; }, abstract = {BACKGROUND: Adjuvant chemotherapy induces weight gain, glucose intolerance, and hypertension in about a third of women. The mechanisms underlying these events have not been defined. This study assessed the association between the microbiome and weight gain in patients treated with adjuvant chemotherapy for breast and gynecological cancers.<br><br>METHODS: Patients were recruited before starting adjuvant therapy. Weight and height were measured before treatment and 4-6&#x2009;weeks after treatment completion. Weight gain was defined as an increase of 3% or more in body weight. A stool sample was collected before treatment, and 16S rRNA gene sequencing was performed. Data regarding oncological therapy, menopausal status, and antibiotic use was prospectively collected. Patients were excluded if they were treated by antibiotics during the study. Fecal transplant experiments from patients were conducted using Swiss Webster germ-free mice.<br><br>RESULTS: Thirty-three patients were recruited; of them, 9 gained 3.5-10.6% of baseline weight. The pretreatment microbiome of women who gained weight following treatment was significantly different in diversity and taxonomy from that of control women. Fecal microbiota transplantation from pretreatment samples of patients that gained weight induced metabolic changes in germ-free mice compared to mice transplanted with pretreatment fecal samples from the control women.<br><br>CONCLUSION: The microbiome composition is predictive of weight gain following adjuvant chemotherapy and induces adverse metabolic changes in germ-free mice, suggesting it contributes to adverse metabolic changes seen in patients. Confirmation of these results in a larger patient cohort is warranted.}, }
@article {pmid33079179, year = {2021}, author = {Quraishi, MN and Iqbal, TH and Hart, AL}, title = {Precision Medicine with FMT for Ulcerative Colitis: Are We There Yet?.}, journal = {Journal of Crohn's &amp; colitis}, volume = {15}, number = {4}, pages = {519-520}, doi = {10.1093/ecco-jcc/jjaa190}, pmid = {33079179}, issn = {1876-4479}, mesh = {Colitis, Ulcerative/genetics/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Genetic Markers ; Humans ; Precision Medicine/*methods ; Treatment Outcome ; }, }
@article {pmid33077775, year = {2020}, author = {Zhang, J and Rodríguez, F and Navas, MJ and Costa-Hurtado, M and Almagro, V and Bosch-Camós, L and López, E and Cuadrado, R and Accensi, F and Pina-Pedrero, S and Martínez, J and Correa-Fiz, F}, title = {Fecal microbiota transplantation from warthog to pig confirms the influence of the gut microbiota on African swine fever susceptibility.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {17605}, pmid = {33077775}, issn = {2045-2322}, mesh = {African Swine Fever/*immunology/virology ; Animals ; Disease Susceptibility ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Sus scrofa ; Swine ; }, abstract = {African swine fever virus (ASFV) is the causative agent of a devastating hemorrhagic disease (ASF) that affects both domestic pigs and wild boars. Conversely, ASFV circulates in a subclinical manner in African wild pigs, including warthogs, the natural reservoir for ASFV. Together with genetic differences, other factors might be involved in the differential susceptibility to ASF observed among Eurasian suids (Sus scrofa) and African warthogs (Phacochoerus africanus). Preliminary evidence obtained in our laboratory and others, seems to confirm the effect that environmental factors might have on ASF infection. Thus, domestic pigs raised in specific pathogen-free (SPF) facilities were extremely susceptible to highly attenuated ASFV strains that were innocuous to genetically identical domestic pigs grown on conventional farms. Since gut microbiota plays important roles in maintaining intestinal homeostasis, regulating immune system maturation and the functionality of the innate/adaptive immune responses, we decided to examine whether warthog fecal microbiota transplantation (FMT) to domestic pigs affects host susceptibility to ASFV. The present work demonstrates that warthog FMT is not harmful for domestic weaned piglets, while it modifies their gut microbiota; and that FMT from warthogs to pigs confers partial protection against attenuated ASFV strains. Future work is needed to elucidate the protective mechanisms exerted by warthog FMT.}, }
@article {pmid33076980, year = {2020}, author = {Hamamoto, Y and Ouhara, K and Munenaga, S and Shoji, M and Ozawa, T and Hisatsune, J and Kado, I and Kajiya, M and Matsuda, S and Kawai, T and Mizuno, N and Fujita, T and Hirata, S and Tanimoto, K and Nakayama, K and Kishi, H and Sugiyama, E and Kurihara, H}, title = {Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model.}, journal = {Arthritis research &amp; therapy}, volume = {22}, number = {1}, pages = {249}, pmid = {33076980}, issn = {1478-6362}, support = {R01 DE029709/DE/NIDCR NIH HHS/United States ; R15 DE027851/DE/NIDCR NIH HHS/United States ; DE029709/DE/NIDCR NIH HHS/United States ; DE027851/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; *Arthritis, Experimental ; Dysbiosis ; Mice ; *Periodontitis ; Porphyromonas gingivalis ; Protein-Arginine Deiminases ; }, abstract = {BACKGROUND: Porphyromonas gingivalis (Pg) infection causes periodontal disease and exacerbates rheumatoid arthritis (RA). It is reported that inoculation of periodontopathogenic bacteria (i.e., Pg) can alter gut microbiota composition in the animal models. Gut microbiota dysbiosis in human has shown strong associations with systemic diseases, including RA, diabetes mellitus, and inflammatory bowel disease. Therefore, this study investigated dysbiosis-mediated arthritis by Pg oral inoculation in an experimental arthritis model mouse.<br><br>METHODS: Pg inoculation in the oral cavity twice a week for 6&#x2009;weeks was performed to induce periodontitis in SKG mice. Concomitantly, a single intraperitoneal (i.p.) injection of laminarin (LA) was administered to induce experimental arthritis (Pg-LA mouse). Citrullinated protein (CP) and IL-6 levels in serum as well as periodontal, intestinal, and joint tissues were measured by ELISA. Gut microbiota composition was determined by pyrosequencing the 16&#x2009;s ribosomal RNA genes after DNA purification of mouse feces. Fecal microbiota transplantation (FMT) was performed by transferring Pg-LA-derived feces to normal SKG mice. The effects of Pg peptidylarginine deiminase (PgPAD) on the level of citrullinated proteins and arthritis progression were determined using a PgPAD knockout mutant.<br><br>RESULTS: Periodontal alveolar bone loss and IL-6 in gingival tissue were induced by Pg oral infection, as well as severe joint destruction, increased arthritis scores (AS), and both IL-6 and CP productions in serum, joint, and intestinal tissues. Distribution of Deferribacteres and S24-7 was decreased, while CP was significantly increased in gingiva, joint, and intestinal tissues of Pg-inoculated experimental arthritis mice compared to experimental arthritis mice without Pg inoculation. Further, FMT from Pg-inoculated experimental arthritis mice reproduced donor gut microbiota and resulted in severe joint destruction with increased IL-6 and CP production in joint and intestinal tissues. The average AS of FMT from Pg-inoculated experimental arthritis was much higher than that of donor mouse. However, inoculation of the PgPAD knockout mutant inhibited the elevation of arthritis scores and ACPA level in serum and reduced CP amount in gingival, joint, and intestinal tissues compared to Pg wild-type inoculation.<br><br>CONCLUSION: Pg oral infection affected gut microbiota dysbiosis and joint destruction via increased CP generation.}, }
@article {pmid33076936, year = {2020}, author = {Dessein, R and Bauduin, M and Grandjean, T and Le Guern, R and Figeac, M and Beury, D and Faure, K and Faveeuw, C and Guery, B and Gosset, P and Kipnis, E}, title = {Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice.}, journal = {Critical care (London, England)}, volume = {24}, number = {1}, pages = {611}, pmid = {33076936}, issn = {1466-609X}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects/pharmacology ; Disease Models, Animal ; Dysbiosis/*complications/etiology/physiopathology ; Immunosuppression Therapy/*adverse effects/methods ; Lung/microbiology/physiopathology ; Mice, Inbred C57BL ; Microbiota/drug effects ; Pneumonia/*etiology/physiopathology ; Pseudomonas aeruginosa/drug effects ; Vancomycin/adverse effects/pharmacology ; }, abstract = {BACKGROUND: Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection.<br><br>METHODS: C57BL6 mice received 7&#x2009;days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2&#x2009;days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24&#x2009;h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow.<br><br>RESULTS: Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection.<br><br>CONCLUSIONS: These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis.}, }
@article {pmid33075447, year = {2021}, author = {Evrensel, A and Tarhan, KN}, title = {Emerging role of Gut-microbiota-brain axis in depression and therapeutic implication.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {106}, number = {}, pages = {110138}, doi = {10.1016/j.pnpbp.2020.110138}, pmid = {33075447}, issn = {1878-4216}, mesh = {Animals ; Brain/immunology/*metabolism ; Brain-Gut Axis/*physiology ; Depression/diet therapy/immunology/*metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Prebiotics/*administration &amp; dosage ; Probiotics/*administration &amp; dosage ; }, abstract = {The human body can be considered a superorganism in which it's eukaryotic cells and prokaryotic microorganisms coexist. Almost every organ system of the body lives a symbiotic life with these commensal bacteria. Intestinal microbiota has an important role in shaping, organizing and maintaining mental functions from as early as the intrauterine period. Microbiota-based approaches are becoming more prominent in understanding and treating the etiopathogenesis of neuropsychiatric disorders, especially depression. Antidepressant drugs, which are the first-line option in the treatment of depression today, also contain antimicrobial and immunomodulatory mechanisms of action. Treatment options for directly modifying the microbiota composition include prebiotics, probiotics (psychobiotics) and fecal microbiota transplantation. There are few preclinical and clinical studies on the efficacy and reliability of these treatment options in depression. This article will review pertinent studies on the role of intestinal microbiota in depression and discuss the treatment potential of altering ones gut microbiome.}, }
@article {pmid33075346, year = {2021}, author = {O'Toole, PW and Shanahan, F}, title = {Transplanting Microbes for Irritable Bowels or Irritated Microbes or Both?.}, journal = {Gastroenterology}, volume = {160}, number = {1}, pages = {15-17}, doi = {10.1053/j.gastro.2020.10.023}, pmid = {33075346}, issn = {1528-0012}, mesh = {*Digestive System Abnormalities ; Fecal Microbiota Transplantation ; Flatulence ; Humans ; *Irritable Bowel Syndrome ; *Transplants ; }, }
@article {pmid33074997, year = {2020}, author = {Calbo, E and Boix-Palop, L and Garau, J}, title = {Clinical and economic impact of bacterial resistance: an approach to infection control and antimicrobial stewardship solutions.}, journal = {Current opinion in infectious diseases}, volume = {33}, number = {6}, pages = {458-463}, pmid = {33074997}, issn = {1473-6527}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Antimicrobial Stewardship/*methods ; Bacteria/drug effects ; Bacterial Infections/drug therapy/*economics/*prevention &amp; control ; *Drug Resistance, Bacterial ; Dysbiosis/epidemiology ; Fecal Microbiota Transplantation/methods ; Gram-Negative Bacteria/drug effects ; Humans ; Infection Control/*methods ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Microbiota/drug effects ; Staphylococcal Infections/drug therapy ; }, abstract = {PURPOSE OF REVIEW: The aim of this study was to describe the clinical and economic burden of bacterial antimicrobial resistance (AMR) and to provide an expert opinion on different approaches to fight it.<br><br>RECENT FINDINGS: For several decades now, it has been known that AMR among human pathogens is related to high clinical and economic burden.Different strategies have been implemented to control the clinical and economic burden of AMR. Antimicrobial stewardship programmes (ASP), environmental cleaning and infection source control have been reported as the most effective interventions. There is a potential role for faecal microbiome transplant (FMT); however, long-term effectiveness and safety remain to be demonstrated. Another promising tool is to develop molecules to chelate or degrade residual antibiotics in the colon. Decolonization has demonstrated impact on methicillin-resistant Staphylococcus aureus (MRSA) infections, but there is limited evidence on the clinical impact and effectiveness of decolonization in MDR Gram-negative carriers.<br><br>SUMMARY: A better assessment of AMR rates and the clinical and economic impact is needed. The epidemiology of AMR bacteria varies in different regions with MRSA, extended-spectrum beta-lactamase and carbapenamase-producing Enterobacterales being the most worrying. ASP and infection control have been increasingly demonstrated to impact on AMR rates. New approaches such as FMT and decolonization have still to demonstrate efficacy and safety.}, }
@article {pmid33073887, year = {2020}, author = {Mossad, O and Erny, D}, title = {The microbiota-microglia axis in central nervous system disorders.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {30}, number = {6}, pages = {1159-1177}, pmid = {33073887}, issn = {1750-3639}, support = {SFB/TRR167//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Central Nervous System Diseases/*pathology ; Gastrointestinal Microbiome/physiology ; Humans ; Microbiota/*physiology ; Microglia/*pathology ; }, abstract = {The innate immune system in the central nervous system (CNS) is mainly represented by specialized tissue-resident macrophages, called microglia. In the past years, various species-, host- and tissue-specific as well as environmental factors were recognized that essentially affect microglial properties and functions in the healthy and diseased brain. Host microbiota are mostly residing in the gut and contribute to microglial activation states, for example, via short-chain fatty acids (SCFAs) or aryl hydrocarbon receptor (AhR) ligands. Thereby, the gut microorganisms are deemed to influence numerous CNS diseases mediated by microglia. In this review, we summarize recent findings of the interaction between the host microbiota and the CNS in health and disease, where we specifically highlight the resident gut microbiota as a crucial environmental factor for microglial function as what we coin "the microbiota-microglia axis."}, }
@article {pmid33073452, year = {2021}, author = {Ankcorn, M and Said, B and Morgan, D and Elsharkawy, AM and Maggs, J and Ryder, S and Valliani, T and Gordon, F and Abeysekera, K and Suri, D and McPherson, S and Galliford, J and Smith, B and Pelosi, E and Bansal, S and Bethune, C and Sheridan, D and Vine, L and Tedder, RS and Ijaz, S and , }, title = {Persistent Hepatitis E virus infection across England and Wales 2009-2017: Demography, virology and outcomes.}, journal = {Journal of viral hepatitis}, volume = {28}, number = {2}, pages = {420-430}, doi = {10.1111/jvh.13424}, pmid = {33073452}, issn = {1365-2893}, mesh = {Demography ; *HIV Infections ; *Hepatitis E/diagnosis/epidemiology ; *Hepatitis E virus/genetics ; Humans ; Immunocompromised Host ; Neoplasm Recurrence, Local ; RNA, Viral ; Retrospective Studies ; Wales/epidemiology ; }, abstract = {The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified through routine reference laboratory testing. Virology, serology and clinical data were recorded through an approved PHE Enhanced Surveillance System. Sixty-six cases (70.2%) were transplant recipients, 16 (17.0%) had an underlying haematological malignancy without stem cell transplantation, six (6.4%) had advanced HIV infection, five (5.3%) were otherwise immunosuppressed, and one patient (1.1%) had no identified immunosuppression. Retrospective analysis of 46 patients demonstrated a median 38 weeks of viraemia before diagnostic HEV testing. At initial diagnosis, 16 patients (17.0%) had no detectable anti-HEV serological response. Of 65 patients treated with ribavirin monotherapy, 11 (16.9%) suffered virological relapse despite undetectable RNA in plasma or stool at treatment cessation. Persistent HEV infection remains a rare diagnosis, but we demonstrate that a broad range of immunocompromised patients are susceptible. Both lack of awareness and the pauci-symptomatic nature of persistent HEV infection likely contribute to significant delays in diagnosis. Diagnosis should rely on molecular testing since anti-HEV serology is insufficient to exclude persistent HEV infection. Finally, despite treatment with ribavirin, relapses occur even after cessation of detectable faecal shedding of HEV RNA, further emphasising the requirement to demonstrate sustained virological responses to treatment.}, }
@article {pmid33071523, year = {2020}, author = {Aslan, AT and Balaban, HY}, title = {Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment.}, journal = {World journal of gastroenterology}, volume = {26}, number = {37}, pages = {5543-5560}, pmid = {33071523}, issn = {2219-2840}, mesh = {Aged ; Aged, 80 and over ; Animals ; Antiviral Agents/therapeutic use ; Female ; *Hepatitis E/diagnosis/drug therapy/epidemiology ; *Hepatitis E virus/genetics ; *Hepatitis, Chronic/drug therapy ; Humans ; Pregnancy ; Ribavirin/therapeutic use ; Swine ; }, abstract = {The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients (e.g., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.}, }
@article {pmid33066233, year = {2020}, author = {Schierová, D and Březina, J and Mrázek, J and Fliegerová, KO and Kvasnová, S and Bajer, L and Drastich, P}, title = {Gut Microbiome Changes in Patients with Active Left-Sided Ulcerative Colitis after Fecal Microbiome Transplantation and Topical 5-aminosalicylic Acid Therapy.}, journal = {Cells}, volume = {9}, number = {10}, pages = {}, pmid = {33066233}, issn = {2073-4409}, mesh = {Administration, Topical ; Adult ; Aged ; Bacteria/classification ; Biodiversity ; Colitis, Ulcerative/drug therapy/*microbiology/*therapy ; Discriminant Analysis ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/drug effects ; Humans ; Male ; Mesalamine/*administration &amp; dosage/pharmacology/*therapeutic use ; Middle Aged ; Principal Component Analysis ; Tissue Donors ; }, abstract = {Ulcerative colitis (UC) is an inflammatory bowel disease, and intestinal bacteria are implicated in the pathogenesis of this disorder. The administration of aminosalicylates (5-ASA) is a conventional treatment that targets the mucosa, while fecal microbial transplantation (FMT) is a novel treatment that directly targets the gut microbiota. The aim of this study was to identify changes in fecal bacterial composition after both types of treatments and evaluate clinical responses. Sixteen patients with active left-sided UC underwent enema treatment using 5-ASA (n = 8) or FMT (n = 8) with a stool from a single donor. Fecal microbiota were analyzed by 16S rDNA high-throughput sequencing, and clinical indices were used to assess the efficacy of treatments. 5-ASA therapy resulted in clinical remission in 50% (4/8) of patients, but no correlation with changes in fecal bacteria was observed. In FMT, remission was achieved in 37.5% (3/8) of patients and was associated with a significantly increased relative abundance of the families Lachnospiraceae, Ruminococcaceae, and Clostridiaceae of the phylum Firmicutes, and Bifidobacteriaceae and Coriobacteriaceae of the phylum Actinobacteria. At the genus level, Faecalibacterium, Blautia, Coriobacteria, Collinsela, Slackia, and Bifidobacterium were significantly more frequent in patients who reached clinical remission. However, the increased abundance of beneficial taxa was not a sufficient factor to achieve clinical improvement in all UC patients. Nevertheless, our preliminary results indicate that FMT as non-drug-using method is thought to be a promising treatment for UC patients.}, }
@article {pmid33066156, year = {2020}, author = {Suganya, K and Koo, BS}, title = {Gut-Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions.}, journal = {International journal of molecular sciences}, volume = {21}, number = {20}, pages = {}, pmid = {33066156}, issn = {1422-0067}, support = {2019R1F1A1060821//National Research Foundation/ ; }, mesh = {Animals ; Brain/immunology/*physiology ; *Gastrointestinal Microbiome ; Humans ; Nervous System Diseases/immunology/*microbiology/prevention &amp; control ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage/therapeutic use ; }, abstract = {The gut microbiome acts as an integral part of the gastrointestinal tract (GIT) that has the largest and vulnerable surface with desirable features to observe foods, nutrients, and environmental factors, as well as to differentiate commensals, invading pathogens, and others. It is well-known that the gut has a strong connection with the central nervous system (CNS) in the context of health and disease. A healthy gut with diverse microbes is vital for normal brain functions and emotional behaviors. In addition, the CNS controls most aspects of the GI physiology. The molecular interaction between the gut/microbiome and CNS is complex and bidirectional, ensuring the maintenance of gut homeostasis and proper digestion. Besides this, several mechanisms have been proposed, including endocrine, neuronal, toll-like receptor, and metabolites-dependent pathways. Changes in the bidirectional relationship between the GIT and CNS are linked with the pathogenesis of gastrointestinal and neurological disorders; therefore, the microbiota/gut-and-brain axis is an emerging and widely accepted concept. In this review, we summarize the recent findings supporting the role of the gut microbiota and immune system on the maintenance of brain functions and the development of neurological disorders. In addition, we highlight the recent advances in improving of neurological diseases by probiotics/prebiotics/synbiotics and fecal microbiota transplantation via the concept of the gut-brain axis.}, }
@article {pmid33064448, year = {2020}, author = {Arulsamy, A and Tan, QY and Balasubramaniam, V and O'Brien, TJ and Shaikh, MF}, title = {Gut Microbiota and Epilepsy: A Systematic Review on Their Relationship and Possible Therapeutics.}, journal = {ACS chemical neuroscience}, volume = {11}, number = {21}, pages = {3488-3498}, doi = {10.1021/acschemneuro.0c00431}, pmid = {33064448}, issn = {1948-7193}, mesh = {Bacteroidetes ; Dysbiosis/therapy ; *Epilepsy/therapy ; *Gastrointestinal Microbiome ; Humans ; Reproducibility of Results ; }, abstract = {Dysbiosis of gut microbiota may lead to a range of diseases including neurological disorders. Thus, it is hypothesized that regulation of the intestinal microbiota may prevent or treat epilepsy. The purpose of this systematic review is to evaluate the evidence investigating the relationship between gut microbiota and epilepsy and possible interventions. A systematic review of the literature was done on four databases (PubMed, Scopus, EMBASE, and Web of Science). Study selection was restricted to original research articles while following the PRISMA guidelines. Six studies were selected. These studies cohesively support the interaction between gut microbiota and epileptic seizures. Gut microbiota analysis identified increases in Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria with decreases in Bacteroidetes and Actinobacteria in epileptic patients. Ketogenic diet, probiotics, and fecal microbiota transplantation (FMT) improved the dysbiosis of the gut microbiota and seizure activity. However, the studies either had a small sample size, lack of subject variability, or short study or follow-up period, which may question their reliability. Nevertheless, these limited studies conclusively suggest that gut microbiota diversity and dysbiosis may be involved in the pathology of epilepsy. Future studies providing more reliable and in depth insight into the gut microbial community will spark promising alternative therapies to current epilepsy treatment.}, }
@article {pmid33057439, year = {2020}, author = {Wendt, R and Nickel, O and Botsch, A and Lindner, M and Bethge, A and Marx, K and Ruf, BR and Beige, J and Lübbert, C}, title = {Low colonization rates with Multidrug-resistant Gram-negative bacteria in a German hospital-affiliated hemodialysis center.}, journal = {PloS one}, volume = {15}, number = {10}, pages = {e0240314}, pmid = {33057439}, issn = {1932-6203}, mesh = {Anti-Bacterial Agents/pharmacology ; Cross-Sectional Studies ; Drug Resistance, Multiple, Bacterial/drug effects ; Feces/microbiology ; Fluoroquinolones/pharmacology ; Germany ; Gram-Negative Bacteria/chemistry/*isolation &amp; purification/metabolism ; Gram-Negative Bacterial Infections/microbiology/*pathology ; Hospitals ; Humans ; Microbial Sensitivity Tests ; Renal Dialysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; beta-Lactamases/metabolism ; }, abstract = {BACKGROUND: Multidrug-resistant Gram-negative bacteria (MDRGN) are found with rising prevalence in non-hemodialysis risk populations as well as hemodialysis (HD) cohorts in Asia, Europe and North America. At the same time, colonization and consecutive infections with such pathogens may increase mortality and morbidity of affected individuals. We aimed to monitor intestinal MDRGN colonization in a yet not investigated German HD population.<br><br>METHODS: We performed cross-sectional point-prevalence testing with 12 months follow-up and selected testing of relatives in an out-patient HD cohort of n = 77 patients by using microbiological cultures from fresh stool samples, combined with Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF-MS) and antimicrobial susceptibility testing.<br><br>RESULTS: We detected MDRGN in 8 out of 77 patients (10.4%) and 1 out of 22 relatives (4.5%), indicating only colonization and no infections. At follow-up, 2 patients showed phenotypic persistence of MDRGN colonization, and in 6 other patients de-novo MDRGN colonization could be demonstrated. Pathogens included Escherichia coli and Klebsiella pneumoniae (with extended-spectrum beta-lactamase [ESBL]-production as well as fluoroquinolone resistance), Stenotrophomonas maltophilia and Enterobacter cloacae.<br><br>CONCLUSIONS: In a single-center study, MDRGN colonization rates were below those found in non-HD high-risk populations and HD units in the US, respectively. Reasons for this could be high hygiene standards and a strict antibiotic stewardship policy with evidence of low consumption of fluoroquinolones and carbapenems in our HD unit and the affiliated hospital.}, }
@article {pmid33055258, year = {2020}, author = {Steed, DB and Wang, T and Raheja, D and Waldman, AD and Babiker, A and Dhere, T and Kraft, CS and Woodworth, MH}, title = {Gram-Negative Taxa and Antimicrobial Susceptibility after Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {33055258}, issn = {2379-5042}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; T32 GM008169/GM/NIGMS NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/drug effects/pathogenicity ; Clostridium Infections/drug therapy/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Gram-Negative Bacteria/*classification/*drug effects/isolation &amp; purification ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has promising applications in reducing multidrug-resistant organism (MDRO) colonization and antibiotic resistance (AR) gene abundance. However, data on clinical microbiology results after FMT are limited. We examined the changes in antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after treatment with FMT for recurrent Clostridioides difficile infection (RCDI). We also examined whether a history of FMT changed health care provider behavior with respect to culture ordering and antibiotic prescription. Medical records for RCDI patients who underwent FMT at Emory University between July 2012 and March 2017 were reviewed retrospectively. FMT-treated patients with Gram-negative culture data in the 1-year period preceding and the 1-year period following FMT were included. Demographic and clinical data were abstracted, including CDI history, frequency of Gram-negative cultures, microbiological results, and antibiotic prescription in response to positive cultures in the period following FMT. Twelve patients were included in this case series. We pooled data from infections at all body sites and found a decrease in the number of total and Gram-negative cultures post-FMT. We compared susceptibility profiles across taxa given the potential for horizontal transmission of AR elements and observed increased susceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, and the aminoglycosides. FMT did not drastically influence health care provider ordering of bacterial cultures or antibiotic prescribing practices. We observed a reduction in Gram-negative cultures and a trend toward increased antimicrobial susceptibility. This study supports further investigation of FMT as a means of improving antimicrobial susceptibility.IMPORTANCE Fecal microbiota transplantation (FMT), which is highly efficacious in treating recurrent C. difficile infection (RCDI), has a promising application in decolonization of multidrug-resistant organisms, reduction of antibiotic resistance gene abundance, and restoration of healthy intestinal microbiota. However, data representing clinical microbiology results after FMT are limited. We sought to characterize the differences in culture positivity and antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after FMT for RCDI. Drawing on prior studies that had demonstrated the success of FMT in eradicating extraintestinal infections and the occurrence of patient-level interspecies transfer of resistance elements, we employed an agnostic analytic approach of reviewing the data irrespective of body site or species. In a small RCDI population, we observed an improvement in the antimicrobial susceptibility profile of Gram-negative bacteria following FMT, which supports further study of FMT as a strategy to combat antibiotic resistance.}, }
@article {pmid33053936, year = {2020}, author = {Sarin, SK and Sharma, S}, title = {Predictors of steroid non-response and new approaches in severe alcoholic hepatitis.}, journal = {Clinical and molecular hepatology}, volume = {26}, number = {4}, pages = {639-651}, pmid = {33053936}, issn = {2287-285X}, mesh = {Biopsy ; Fecal Microbiota Transplantation ; Granulocyte Colony-Stimulating Factor ; *Hepatitis, Alcoholic ; Humans ; Steroids ; }, abstract = {Severe alcoholic hepatitis (SAH) remains a disease with high mortality. Steroid is the main stay and has been shown to give modest 28-day survival benefit in carefully selected patients, but no 90-day survival benefit. Since non-responders have high incidence of infections and increased mortality, it would be worthwhile to identify them before starting steroid therapy. A high and rising bilirubin, urinary acetyl carnitine >2,500 ng/mL, high asiloglycoprotein positive microparticles, and specific features in liver biopsy could predict steroid non-response at baseline. There is an ever-growing need to find new and effective therapies for SAH patients. Besides aggressive nutrition, granulocyte colony stimulating factor, fecal microbiota transplantation, and plasma exchange appear promising therapies and provide a hope for steroid ineligible or steroid non-responsive patients. Suppression of hepatic inflammation, preventing new bacterial or fungal infections, and enhancing liver regeneration will remain the key targets for next generation therapies.}, }
@article {pmid33053357, year = {2020}, author = {Leclercq, S and Le Roy, T and Furgiuele, S and Coste, V and Bindels, LB and Leyrolle, Q and Neyrinck, AM and Quoilin, C and Amadieu, C and Petit, G and Dricot, L and Tagliatti, V and Cani, PD and Verbeke, K and Colet, JM and Stärkel, P and de Timary, P and Delzenne, NM}, title = {Gut Microbiota-Induced Changes in β-Hydroxybutyrate Metabolism Are Linked to Altered Sociability and Depression in Alcohol Use Disorder.}, journal = {Cell reports}, volume = {33}, number = {2}, pages = {108238}, doi = {10.1016/j.celrep.2020.108238}, pmid = {33053357}, issn = {2211-1247}, mesh = {3-Hydroxybutyric Acid/blood/*metabolism ; Alcoholism/blood/*complications/*microbiology ; Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Behavior, Animal/drug effects ; Brain/physiopathology ; Depression/blood/*complications/*microbiology ; Diet, Ketogenic ; Dysbiosis/blood/complications/microbiology ; Ethanol ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Homeostasis/drug effects ; Humans ; Inflammation/blood/complications ; Intestines/drug effects/pathology ; Lipolysis/drug effects ; Liver/drug effects/metabolism ; Male ; Metabolic Networks and Pathways/drug effects ; Mice, Inbred C57BL ; Myelin Sheath/metabolism ; Permeability ; *Social Behavior ; Tissue Donors ; }, abstract = {Patients with alcohol use disorder (AUD) present with important emotional, cognitive, and social impairments. The gut microbiota has been recently shown to regulate brain functions and behavior but convincing evidence of its role in AUD is lacking. Here, we show that gut dysbiosis is associated with metabolic alterations that affect behavioral (depression, sociability) and neurobiological (myelination, neurotransmission, inflammation) processes involved in alcohol addiction. By transplanting the gut microbiota from AUD patients to mice, we point out that the production of ethanol by specific bacterial genera and the reduction of lipolysis are associated with a lower hepatic synthesis of β-hydroxybutyrate (BHB), which thereby prevents the neuroprotective effect of BHB. We confirm these results in detoxified AUD patients, in which we observe a persisting ethanol production in the feces as well as correlations among low plasma BHB levels and social impairments, depression, or brain white matter alterations.}, }
@article {pmid33051451, year = {2020}, author = {Wang, H and Liu, L and Rao, X and Zeng, B and Yu, Y and Zhou, C and Zeng, L and Zheng, P and Pu, J and Xu, S and Cheng, K and Zhang, H and Ji, P and Wei, H and Xie, P}, title = {Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice.}, journal = {Translational psychiatry}, volume = {10}, number = {1}, pages = {346}, pmid = {33051451}, issn = {2158-3188}, mesh = {Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Hippocampus ; Mice ; *Microbiota ; }, abstract = {The dysbiosis of gut microbiota is an important environmental factor that can induce mental disorders, such as depression, through the microbiota-gut-brain axis. However, the underlying pathogenic mechanisms are complex and not completely understood. Here we utilized mass spectrometry to identify the global phosphorylation dynamics in hippocampus tissue in germ-free mice and specific pathogen-free mice (GF vs SPF), fecal microbiota transplantation (FMT) model ("depression microbiota" and the "healthy microbiota" recipient mice). As a result, 327 phosphosites of 237 proteins in GF vs SPF, and 478 phosphosites of 334 proteins in "depression microbiota" vs "healthy microbiota" recipient mice were identified as significant. These phosphorylation dysregulations were consistently associated with glutamatergic neurotransmitter system disturbances. The FMT mice exhibited disturbances in lipid metabolism and amino acid metabolism in both the periphery and brain through integrating phosphoproteomic and metabolomic analysis. Moreover, CAMKII-CREB signaling pathway, in response to these disturbances, was the primary common perturbed cellular process. In addition, we demonstrated that the spliceosome, never directly implicated in mental disorders previously, was a substantially neuronal function disrupted by gut microbiota dysbiosis, and the NCBP1 phosphorylation was identified as a novel pathogenic target. These results present a new perspective to study the pathologic mechanisms of gut microbiota dysbiosis related depression and highlight potential gut-mediated therapies for depression.}, }
@article {pmid33051190, year = {2021}, author = {Fassarella, M and Blaak, EE and Penders, J and Nauta, A and Smidt, H and Zoetendal, EG}, title = {Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health.}, journal = {Gut}, volume = {70}, number = {3}, pages = {595-605}, doi = {10.1136/gutjnl-2020-321747}, pmid = {33051190}, issn = {1468-3288}, mesh = {Anti-Bacterial Agents/adverse effects ; Biodiversity ; Diet ; Dysbiosis/etiology/prevention &amp; control ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions ; Humans ; Probiotics/therapeutic use ; }, abstract = {The human gut microbiome is a complex ecosystem, densely colonised by thousands of microbial species. It varies among individuals and depends on host genotype and environmental factors, such as diet and antibiotics. In this review, we focus on stability and resilience as essential ecological characteristics of the gut microbiome and its relevance for human health. Microbial diversity, metabolic flexibility, functional redundancy, microbe-microbe and host-microbe interactions seem to be critical for maintaining resilience. The equilibrium of the gut ecosystem can be disrupted by perturbations, such as antibiotic therapy, causing significant decreases in functional richness and microbial diversity as well as impacting metabolic health. As a consequence, unbalanced states or even unhealthy stable states can develop, potentially leading to or supporting diseases. Accordingly, strategies have been developed to manipulate the gut microbiome in order to prevent or revert unhealthy states caused by perturbations, including faecal microbiota transplantation, supplementation with probiotics or non-digestible carbohydrates, and more extensive dietary modifications. Nevertheless, an increasing number of studies has evidenced interindividual variability in extent and direction of response to diet and perturbations, which has been attributed to the unique characteristics of each individual's microbiome. From a clinical, translational perspective, the ability to improve resilience of the gut microbial ecosystem prior to perturbations, or to restore its equilibrium afterwards, would offer significant benefits. To be effective, this therapeutic approach will likely need a personalised or subgroup-based understanding of individual genetics, diet, gut microbiome and other environmental factors that might be involved.}, }
@article {pmid33046129, year = {2020}, author = {Binyamin, D and Werbner, N and Nuriel-Ohayon, M and Uzan, A and Mor, H and Abbas, A and Ziv, O and Teperino, R and Gutman, R and Koren, O}, title = {The aging mouse microbiome has obesogenic characteristics.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {87}, pmid = {33046129}, issn = {1756-994X}, mesh = {Age Factors ; *Aging/metabolism ; Animals ; Biodiversity ; Disease Models, Animal ; *Disease Susceptibility ; Energy Metabolism ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Male ; Mice ; *Microbiota ; Obesity/*etiology/metabolism ; Phenotype ; }, abstract = {BACKGROUND: During aging, there is a physiological decline, an increase of morbidity and mortality, and a natural change in the gut microbiome. In this study, we investigated the influence of the gut microbiome on different metabolic parameters in adult and aged mice.<br><br>METHODS: Fecal and blood samples from adult (n&#x2009;=&#x2009;42, 100-300&#x2009;days) and aging (n&#x2009;=&#x2009;32, 550-750&#x2009;days) mice were collected. Microbiome analysis was done using QIIME2. Mouse weight and body composition were measured using NMR, and insulin and leptin levels in the blood were measured with Mouse Adipokine Magnetic Bead Panel kit. Fecal microbiota transplantation experiments from adult and aged mice into young germ-free mice were carried out in order to examine the effect of the gut microbiome of adult and aging mice on weight, body composition, insulin, and leptin.<br><br>RESULTS: We demonstrate that the microbiomes from adult and aged mice are distinguishable. We also report changes in metabolic parameters as we observed significantly higher weight and fat mass and low lean mass in aged compared to adult mice along with high insulin and leptin levels in the blood. The transplanted gut microbiome from aged mice transferred part of the phenotypes seen in aged mice. Fat body mass and insulin levels were higher in the mice who received feces from aged mice than mice receiving feces from adult mice. In addition, they consumed more food and had a higher respiratory quotient compared to mice receiving adult feces.<br><br>CONCLUSIONS: We conclude that aged mice have a gut microbiota with obesogenic characteristics. In addition, the gut bacterial population itself is sufficient to induce some of the manifestations of obesity.}, }
@article {pmid33045322, year = {2021}, author = {Bioque, M and González-Rodríguez, A and Garcia-Rizo, C and Cobo, J and Monreal, JA and Usall, J and Soria, V and ,  and Labad, J}, title = {Targeting the microbiome-gut-brain axis for improving cognition in schizophrenia and major mood disorders: A narrative review.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {105}, number = {}, pages = {110130}, doi = {10.1016/j.pnpbp.2020.110130}, pmid = {33045322}, issn = {1878-4216}, mesh = {Brain-Gut Axis/*physiology ; Cognition/*physiology ; Humans ; Microbiota/*physiology ; Mood Disorders/microbiology/*psychology ; Probiotics/therapeutic use ; Schizophrenia/*microbiology ; *Schizophrenic Psychology ; }, abstract = {Cognitive impairment has been consistently found to be a core feature of serious mental illnesses such as schizophrenia and major mood disorders (major depression and bipolar disorder). In recent years, a great effort has been made in elucidating the biological causes of cognitive deficits and the search for new biomarkers of cognition. Microbiome and gut-brain axis (MGB) hormones have been postulated to be potential biomarkers of cognition in serious mental illnesses. The main aim of this review was to synthesize current evidence on the association of microbiome and gut-brain hormones on cognitive processes in schizophrenia and major mood disorders and the association of MGB hormones with stress and the immune system. Our review underscores the role of the MGB axis on cognitive aspects of serious mental illnesses with the potential use of agents targeting the gut microbiota as cognitive enhancers. However, the current evidence for clinical trials focused on the MGB axis as cognitive enhancers in these clinical populations is scarce. Future clinical trials using probiotics, prebiotics, antibiotics, or faecal microbiota transplantation need to consider potential mechanistic pathways such as the HPA axis, the immune system, or gut-brain axis hormones involved in appetite control and energy homeostasis.}, }
@article {pmid33044577, year = {2020}, author = {Gerdes, LA and Yoon, H and Peters, A}, title = {[Microbiota and multiple sclerosis].}, journal = {Der Nervenarzt}, volume = {91}, number = {12}, pages = {1096-1107}, doi = {10.1007/s00115-020-01012-w}, pmid = {33044577}, issn = {1433-0407}, mesh = {Animals ; Central Nervous System ; *Encephalomyelitis, Autoimmune, Experimental ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Multiple Sclerosis ; }, abstract = {Multiple sclerosis (MS) is an inflammatory disease of the central nervous system driven by autoreactive lymphocytes. Due to its close contact with the gut-associated lymphoid tissue, the intestinal microbiota and/or their metabolites may be one of the factors that influence the activation of autoreactive lymphocytes. This article summarizes and discusses the current research efforts to characterize the microbiome of MS patients using human material. In addition, we present research studies that utilized classical or humanized animal models to determine the influence of certain microbiota species or compositions of microbiota on the immune system and disease progression and to define possible causal associations.}, }
@article {pmid33042284, year = {2020}, author = {Xu, Y and Wang, N and Tan, HY and Li, S and Zhang, C and Zhang, Z and Feng, Y}, title = {Panax notoginseng saponins modulate the gut microbiota to promote thermogenesis and beige adipocyte reconstruction via leptin-mediated AMPKα/STAT3 signaling in diet-induced obesity.}, journal = {Theranostics}, volume = {10}, number = {24}, pages = {11302-11323}, pmid = {33042284}, issn = {1838-7640}, mesh = {AMP-Activated Protein Kinases/metabolism ; Adipocytes, Beige/drug effects/metabolism ; Adipose Tissue, White/cytology/drug effects/metabolism ; Akkermansia/genetics/isolation &amp; purification ; Animals ; Bacteroidetes/genetics/isolation &amp; purification ; Body Composition ; DNA, Bacterial/isolation &amp; purification ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Energy Metabolism/drug effects ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Leptin/metabolism ; Male ; Mice ; Mice, Obese ; Obesity/*drug therapy/etiology/pathology ; Panax notoginseng/*chemistry ; RNA, Ribosomal, 16S/genetics ; STAT3 Transcription Factor/metabolism ; Saponins/*administration &amp; dosage ; Signal Transduction/drug effects ; Thermogenesis/*drug effects ; }, abstract = {Background: Activation of the thermogenic program in white and brown adipocytes presents a promising avenue for increasing energy expenditure during the treatment of obesity. The endogenous mechanism for promoting thermogenesis in brown adipocytes or browning in white adipocytes has indicated that the gut microbiota is a crucial regulator of the host energy balance. However, whether the effects of the therapeutic intervention-induced modulation of the gut microbiota on adipocyte browning involved the regulation of leptin remains unclear. Method: The adipose features were analyzed by body composition analysis, infrared camera observations, transmission electron microscopy and H&amp;E staining. The gene and protein expression in adipose tissue were detected by qRT-PCR, immunoblotting, immunohistochemistry and immunofluorescence staining. The gut microbiome signature was identified by 16S rRNA gene amplicon sequencing, and both mice with high-fat diet-induced obesity (DIO) and mice with antibiotics-induced microbiome depletion were subjected to fecal microbiota transplantation. Results: Treatment with Panax notoginseng saponins (PNS) shaped the murine gut microbiome by increasing the abundances of Akkermansia muciniphila and Parabacteroides distasonis, and as a result, DIO mice harbored a distal gut microbiota with a significantly increased capacity to reduce host adiposity. The PNS-induced modulation of the gut microbiota in DIO mice could increase brown adipose tissue (BAT) thermogenesis and beige adipocyte reconstruction by activating the leptin-AMPK/STAT3 signaling pathway, which results in the promotion of energy expenditure. Leptin has an essential influence on the anti-obesity effects of PNS. In cases of leptin deficiency, the PNS-induced modulation of the gut microbiota exerts negative effects on thermogenesis and browning in white adipose tissue (WAT), which indicates that PNS fail to reduce obesity in leptin gene-deficient mice. The PNS-induced modulation of the gut microbiota exerted a minimal effect on DIO mice with antibiotic-induced microbiome depletion, which confirmed the correlation between altered gut microbiota and the remodeling of adipose tissues in DIO mice. The direct influence of leptin on browning via the AMPKα/STAT3 signaling pathway in C3H101/2 cells supported our in vivo results that signalling through the leptin-AMPK/STAT3 pathway induced by the PNS-modulated gut microbiota was involved in beige adipocyte reconstruction. Conclusion: Our results revealed that leptin signaling is critical for alterations in microbiota-fat crosstalk and provide promising avenues for therapeutic intervention in the treatment of obesity.}, }
@article {pmid33042155, year = {2020}, author = {Macpherson, ME and Hov, JR and Ueland, T and Dahl, TB and Kummen, M and Otterdal, K and Holm, K and Berge, RK and Mollnes, TE and Trøseid, M and Halvorsen, B and Aukrust, P and Fevang, B and Jørgensen, SF}, title = {Gut Microbiota-Dependent Trimethylamine N-Oxide Associates With Inflammation in Common Variable Immunodeficiency.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {574500}, pmid = {33042155}, issn = {1664-3224}, mesh = {Adult ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Bacterial Proteins/genetics/metabolism ; Biomarkers/blood ; Carnitine/metabolism ; Common Variable Immunodeficiency/*blood/drug therapy/immunology/microbiology ; Diet ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Humans ; Immunoglobulin A, Secretory/blood ; Inflammation ; Lipopolysaccharides/blood ; Male ; Metabolic Networks and Pathways ; Methylamines/*blood/metabolism ; Middle Aged ; Rifaximin/administration &amp; dosage ; }, abstract = {A substantial proportion of patients with common variable immunodeficiency (CVID) have inflammatory and autoimmune complications of unknown etiology. We have previously shown that systemic inflammation in CVID correlates with their gut microbial dysbiosis. The gut microbiota dependent metabolite trimethylamine N-oxide (TMAO) has been linked to several metabolic and inflammatory disorders, but has hitherto not been investigated in relation to CVID. We hypothesized that TMAO is involved in systemic inflammation in CVID. To explore this, we measured plasma concentrations of TMAO, inflammatory markers, and lipopolysaccharide (LPS) in 104 CVID patients and 30 controls. Gut microbiota profiles and the bacterial genes CutC and CntA, which encode enzymes that can convert dietary metabolites to trimethylamine in the colon, were examined in fecal samples from 40 CVID patients and 86 controls. Furthermore, a food frequency questionnaire and the effect of oral antibiotic rifaximin on plasma TMAO concentrations were explored in these 40 patients. We found CVID patients to have higher plasma concentrations of TMAO than controls (TMAO 5.0 [2.9-8.6] vs. 3.2 [2.2-6.3], p = 0.022, median with IQR). The TMAO concentration correlated positively with tumor necrosis factor (p = 0.008, rho = 0.26), interleukin-12 (p = 0.012, rho = 0.25) and LPS (p = 0.034, rho = 0.21). Dietary intake of meat (p = 0.678), fish (p = 0.715), egg (p = 0.138), dairy products (p = 0.284), and fiber (p = 0.767) did not significantly impact on the TMAO concentrations in plasma, nor did a 2-week course of the oral antibiotic rifaximin (p = 0.975). However, plasma TMAO concentrations correlated positively with gut microbial abundance of Gammaproteobacteria (p = 0.021, rho = 0.36). Bacterial gene CntA was present in significantly more CVID samples (75%) than controls (53%), p = 0.020, potentially related to the increased abundance of Gammaproteobacteria in these samples. The current study demonstrates that elevated TMAO concentrations are associated with systemic inflammation and increased gut microbial abundance of Gammaproteobacteria in CVID patients, suggesting that TMAO could be a link between gut microbial dysbiosis and systemic inflammation. Gut microbiota composition could thus be a potential therapeutic target to reduce systemic inflammation in CVID.}, }
@article {pmid33042125, year = {2020}, author = {Raftery, AL and Tsantikos, E and Harris, NL and Hibbs, ML}, title = {Links Between Inflammatory Bowel Disease and Chronic Obstructive Pulmonary Disease.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {2144}, pmid = {33042125}, issn = {1664-3224}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects ; Autophagy ; Bacteria/metabolism ; Cigarette Smoking/adverse effects ; Dietary Fats/pharmacology ; Dietary Fiber/pharmacology ; Disease Models, Animal ; Dysbiosis/*immunology/microbiology/therapy ; Fatty Acids, Volatile/pharmacology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/immunology ; Gene-Environment Interaction ; Humans ; Immunity, Mucosal/immunology ; Inflammation ; Inflammatory Bowel Diseases/immunology/*microbiology/therapy ; Intestines/embryology/immunology/microbiology/virology ; Lung/embryology/immunology/microbiology/virology ; Mice ; Microbiota/drug effects/*immunology ; Pulmonary Disease, Chronic Obstructive/drug therapy/immunology/*microbiology ; Tobacco Smoke Pollution/adverse effects ; Vitamin D/pharmacology/therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the gastrointestinal and respiratory tracts, respectively. These mucosal tissues bear commonalities in embryology, structure and physiology. Inherent similarities in immune responses at the two sites, as well as overlapping environmental risk factors, help to explain the increase in prevalence of IBD amongst COPD patients. Over the past decade, a tremendous amount of research has been conducted to define the microbiological makeup of the intestine, known as the intestinal microbiota, and determine its contribution to health and disease. Intestinal microbial dysbiosis is now known to be associated with IBD where it impacts upon intestinal epithelial barrier integrity and leads to augmented immune responses and the perpetuation of chronic inflammation. While much less is known about the lung microbiota, like the intestine, it has its own distinct, diverse microflora, with dysbiosis being reported in respiratory disease settings such as COPD. Recent research has begun to delineate the interaction or crosstalk between the lung and the intestine and how this may influence, or be influenced by, the microbiota. It is now known that microbial products and metabolites can be transferred from the intestine to the lung via the bloodstream, providing a mechanism for communication. While recent studies indicate that intestinal microbiota can influence respiratory health, intestinal dysbiosis in COPD has not yet been described although it is anticipated since factors that lead to dysbiosis are similarly associated with COPD. This review will focus on the gut-lung axis in the context of IBD and COPD, highlighting the role of environmental and genetic factors and the impact of microbial dysbiosis on chronic inflammation in the intestinal tract and lung.}, }
@article {pmid33041818, year = {2020}, author = {Tan, P and Li, X and Shen, J and Feng, Q}, title = {Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease: An Update.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {574533}, pmid = {33041818}, issn = {1663-9812}, abstract = {Fecal microbiota transplantation (FMT) has successfully been applied for the treatment of recurrent Clostridioides difficile infection (CDI), which has led to studies on its application to other gastrointestinal diseases and extraintestinal diseases associated with gut microbiota dysbiosis. Recently, the results of FMT for patients with inflammatory bowel disease (IBD) have been encouraging. However, studies have not fully clarified the clinical application of this emerging therapy. Here, we aimed to review the current knowledge in this fast-growing field and characterize the effectiveness, safety and mechanisms of FMT for the treatment of IBD patients.}, }
@article {pmid33039712, year = {2020}, author = {Li, X and Lin, Y and Li, X and Xu, X and Zhao, Y and Xu, L and Gao, Y and Li, Y and Tan, Y and Qian, P and Huang, H}, title = {Tyrosine supplement ameliorates murine aGVHD by modulation of gut microbiome and metabolome.}, journal = {EBioMedicine}, volume = {61}, number = {}, pages = {103048}, pmid = {33039712}, issn = {2352-3964}, mesh = {Acute Disease ; Animals ; Biodiversity ; Chromatography, High Pressure Liquid ; Computational Biology/methods ; *Dietary Supplements ; Disease Management ; Disease Models, Animal ; Disease Susceptibility ; *Gastrointestinal Microbiome ; Graft vs Host Disease/diagnosis/*etiology/*metabolism/therapy ; Intestinal Mucosa ; Mass Spectrometry/methods ; *Metabolome ; Metabolomics/methods ; Metagenomics/methods ; Mice ; Phenotype ; RNA, Ribosomal, 16S/genetics ; Tyrosine/*administration &amp; dosage ; }, abstract = {BACKGROUND: Microbial communities and their metabolic components in the gut are of vital importance for immune homeostasis and have an influence on the susceptibility of the host to a number of immune-mediated diseases like acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the functional connections between microbiome and metabolome in aGVHD due to the complexity of the gastrointestinal environment.<br><br>METHOD: Initially, gut microbiota and fecal metabolic phenotype in aGVHD murine models were unleashed by performing 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics.<br><br>FINDINGS: The group with aGVHD experienced a significant drop in Lachnospiraceae_unclassified but an increase in the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites were inversely correlated with Clostridium XIVa, besides, Blautia and Enterococcus also displayed the negative tendency in aGVHD condition. Apart from exploring the importance and function of tyrosine, different tyrosine diets were offered to mice during transplantation. Additional tyrosine supplements can improve overall survival, ameliorate symptoms at the early stage of aGVHD and change the structure and composition of gut microbiota and fecal metabolic phenotype. In addition, aGVHD mice deprived from tyrosine displayed worse manifestations than the vehicle diet group.<br><br>INTERPRETATION: The results demonstrated the roles and mechanisms of gut microbiota, indispensable metabolites and tyrosine in the progression of aGVHD, which can be an underlying biomarker for aGVHD diagnosis and treatment.<br><br>FUNDING: This research was funded by the International Cooperation and Exchange Program (81520108002), the National Key R&amp;D Program of China, Stem Cell and Translation Research (2018YFA0109300), National Natural Science Foundation of China (81670169, 81670148, 81870080 and 91949115) and Natural Science Foundation of Zhejiang Province (LQ19H080006).}, }
@article {pmid33036625, year = {2020}, author = {Liu, H and Tian, R and Wang, H and Feng, S and Li, H and Xiao, Y and Luan, X and Zhang, Z and Shi, N and Niu, H and Zhang, S}, title = {Gut microbiota from coronary artery disease patients contributes to vascular dysfunction in mice by regulating bile acid metabolism and immune activation.}, journal = {Journal of translational medicine}, volume = {18}, number = {1}, pages = {382}, pmid = {33036625}, issn = {1479-5876}, mesh = {Animals ; Bile Acids and Salts ; *Coronary Artery Disease ; *Gastrointestinal Microbiome ; Humans ; Lipid Metabolism ; Mice ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: The gut microbiota was shown to play a crucial role in the development of vascular dysfunction, and the bacterial composition differed between healthy controls and coronary artery disease patients. The goal of this study was to investigate how the gut microbiota affects host metabolic homeostasis at the organism scale.<br><br>METHODS: We colonized germ-free C57BL/6 J mice with faeces from healthy control donors (Con) and coronary artery disease (CAD) patients and fed both groups a high fat diet for 12&#xa0;weeks. We monitored cholesterol and vascular function in the transplanted mice. We analysed bile acids profiles and gut microbiota composition. Transcriptome sequencing and flow cytometry were performed to evaluate inflammatory and immune response.<br><br>RESULTS: CAD mice showed increased reactive oxygen species generation and intensive arterial stiffness. Microbiota profiles in recipient mice clustered according to the microbiota structure of the human donors. Clostridium symbiosum and Eggerthella colonization from CAD patients modulated the secondary bile acids pool, leading to an increase in lithocholic acid and keto-derivatives. Subsequently, bile acids imbalance in the CAD mice inhibited hepatic bile acids synthesis and resulted in elevated circulatory cholesterol. Moreover, the faecal microbiota from the CAD patients caused a significant induction of abnormal immune responses at both the transcriptome level and through the enhanced secretion of cytokines. In addition, microbes belonging to CAD promoted intestinal inflammation by contributing to lamina propria Th17/Treg imbalance and worsened gut barrier permeability.<br><br>CONCLUSIONS: In summary, our findings elucidated that the gut microbiota impacts cholesterol homeostasis by modulating bile acids. In addition, the CAD-associated bacterial community was shown to function as an important regulator of systemic inflammation and to influence arterial stiffness.}, }
@article {pmid33035780, year = {2020}, author = {Haifer, C and Leong, RW and Paramsothy, S}, title = {The role of faecal microbiota transplantation in the treatment of inflammatory bowel disease.}, journal = {Current opinion in pharmacology}, volume = {55}, number = {}, pages = {8-16}, pmid = {33035780}, issn = {1471-4973}, mesh = {Clostridioides difficile ; Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*therapy ; }, abstract = {PURPOSE OF THE REVIEW: Faecal microbiota transplantation (FMT) has emerged as a potent form of therapeutic microbial manipulation. There is much interest in exploring its potential in conditions such as inflammatory bowel disease (IBD) where disturbances in the gastrointestinal microbiota play a crucial role in disease pathogenesis.<br><br>RECENT FINDINGS: There are 4 randomized controlled trials of FMT as induction therapy in ulcerative colitis, with meta-analyses suggesting significant benefit over placebo. Allied microbial studies have identified potential microbial and metabolic predictors of therapeutic efficacy and highlighted the importance of optimizing future donor and patient selection. Recent literature has evaluated the use of complementary microbial manipulation through pre-antibiotics to improve treatment efficacy. Studies have also assessed the durability of FMT response and its use in maintenance therapy of UC. While data on FMT are more limited in Crohn's disease and pouchitis, cohort and pilot randomized controlled data a now also emerging in these areas.}, }
@article {pmid33034846, year = {2020}, author = {Brown, EG and Goldman, SM}, title = {Modulation of the Microbiome in Parkinson's Disease: Diet, Drug, Stool Transplant, and Beyond.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {17}, number = {4}, pages = {1406-1417}, pmid = {33034846}, issn = {1878-7479}, mesh = {Animals ; Antiparkinson Agents/*administration &amp; dosage ; Diet, Vegetarian/*methods ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Parkinson Disease/diagnosis/physiopathology/*therapy ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; }, abstract = {The gastrointestinal microbiome is altered in Parkinson's disease and likely plays a key role in its pathophysiology, affecting symptoms and response to therapy and perhaps modifying progression or even disease initiation. Gut dysbiosis therefore has a significant potential as a therapeutic target in Parkinson's disease, a condition elusive to disease-modifying therapy thus far. The gastrointestinal environment hosts a complex ecology, and efforts to modulate the relative abundance or function of established microorganisms are still in their infancy. Still, these techniques are being rapidly developed and have important implications for our understanding of Parkinson's disease. Currently, modulation of the microbiome can be achieved through non-pharmacologic means such as diet, pharmacologically through probiotic, prebiotic, or antibiotic use and procedurally through fecal transplant. Novel techniques being explored include the use of small molecules or genetically engineered organisms, with vast potential. Here, we review how some of these approaches have been used to date, important areas of ongoing research, and how microbiome modulation may play a role in the clinical management of Parkinson's disease in the future.}, }
@article {pmid33033580, year = {2020}, author = {Nie, X and Chen, J and Ma, X and Ni, Y and Shen, Y and Yu, H and Panagiotou, G and Bao, Y}, title = {A metagenome-wide association study of gut microbiome and visceral fat accumulation.}, journal = {Computational and structural biotechnology journal}, volume = {18}, number = {}, pages = {2596-2609}, pmid = {33033580}, issn = {2001-0370}, abstract = {PURPOSE: Visceral fat is an independent risk factor for metabolic and cardiovascular disease. The study aimed to investigate the associations between gut microbiome and visceral fat.<br><br>METHODS: We recruited 32 obese adults and 30 healthy controls at baseline. Among the obese subjects, 14 subjects underwent laparoscopic sleeve gastrectomy (LSG) and were followed 6&#xa0;months after surgery. Abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by magnetic resonance imaging. Waist, hipline, waist-to-hip ratio (WHR) and body mass index (BMI) were included as simple obese parameters. Gut microbiome was analyzed by metagenomic sequencing.<br><br>RESULTS: Among the obese parameters, VFA had the largest number of correlations with the species that were differentially enriched between obese and healthy subjects, following by waist, WHR, BMI, hipline, and SFA. Within the species negatively correlated with VFA, Eubacterium eligens had the strongest correlation, following by Clostridium citroniae, C. symbiosum, Bacteroides uniformis, E. ventriosum, Ruminococcaceae bacterium D16, C. hathewayi, etc. C. hathewayi and C. citroniae were increased after LSG. Functional analyses showed that among all the obese parameters, VFA had strongest correlation coefficients with the obesity-related microbial pathways. Microbial pathways involved in carbohydrate fermentation and biosynthesis of L-glutamate and L-glutamine might contribute to visceral fat accumulation.<br><br>CONCLUSIONS: Visceral fat was more closely correlated with gut microbiome compared with subcutaneous fat, suggesting an intrinsic connection between gut microbiome and metabolic cardiovascular diseases. Specific microbial species and pathways which were closely associated with visceral fat accumulation might contribute to new targeted therapies for metabolic disorders.}, }
@article {pmid33027674, year = {2020}, author = {Arnoriaga-Rodríguez, M and Mayneris-Perxachs, J and Burokas, A and Contreras-Rodríguez, O and Blasco, G and Coll, C and Biarnés, C and Miranda-Olivos, R and Latorre, J and Moreno-Navarrete, JM and Castells-Nobau, A and Sabater, M and Palomo-Buitrago, ME and Puig, J and Pedraza, S and Gich, J and Pérez-Brocal, V and Ricart, W and Moya, A and Fernández-Real, X and Ramió-Torrentà, L and Pamplona, R and Sol, J and Jové, M and Portero-Otin, M and Maldonado, R and Fernández-Real, JM}, title = {Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids.}, journal = {Cell metabolism}, volume = {32}, number = {4}, pages = {548-560.e7}, doi = {10.1016/j.cmet.2020.09.002}, pmid = {33027674}, issn = {1932-7420}, mesh = {Adult ; Aged ; Amino Acids, Aromatic/*metabolism ; Animals ; Case-Control Studies ; Cross-Sectional Studies ; Female ; *Gastrointestinal Microbiome ; Humans ; Magnetic Resonance Imaging ; Male ; *Memory, Short-Term ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Obesity/*metabolism ; }, abstract = {The gut microbiome has been linked to fear extinction learning in animal models. Here, we aimed to explore the gut microbiome and memory domains according to obesity status. A specific microbiome profile associated with short-term memory, working memory, and the volume of the hippocampus and frontal regions of the brain differentially in human subjects with and without obesity. Plasma and fecal levels of aromatic amino acids, their catabolites, and vegetable-derived compounds were longitudinally associated with short-term and working memory. Functionally, microbiota transplantation from human subjects with obesity led to decreased memory scores in mice, aligning this trait from humans with that of recipient mice. RNA sequencing of the medial prefrontal cortex of mice revealed that short-term memory associated with aromatic amino acid pathways, inflammatory genes, and clusters of bacterial species. These results highlight the potential therapeutic value of targeting the gut microbiota for memory impairment, specifically in subjects with obesity.}, }
@article {pmid33024394, year = {2020}, author = {Wu, YN and Zhang, L and Chen, T and Li, X and He, LH and Liu, GX}, title = {Granulocyte-macrophage colony-stimulating factor protects mice against hepatocellular carcinoma by ameliorating intestinal dysbiosis and attenuating inflammation.}, journal = {World journal of gastroenterology}, volume = {26}, number = {36}, pages = {5420-5436}, pmid = {33024394}, issn = {2219-2840}, mesh = {Animals ; *Carcinoma, Hepatocellular/prevention &amp; control ; Dysbiosis/prevention &amp; control ; Granulocyte-Macrophage Colony-Stimulating Factor ; Inflammation ; *Liver Neoplasms/prevention &amp; control ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. The gut microbiota can help maintain healthy metabolism and immunity. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical factor in promoting health and homeostasis; it promotes intestinal immunity, stimulates bone marrow precursors to generate macrophage colonies, and enhances the antibacterial and antitumor activity of circulating monocytes. As such, GM-CSF may protect against HCC development by regulating immunity as well as intestinal microecology.<br><br>AIM: To investigate the impact of GM-CSF on the gut microbiome and metabolic characteristics of HCC.<br><br>METHODS: Thirty-six male BALB/c nude mice were divided into three groups: Control (n = 10), HCC (n = 13), and HCC + GM-CSF (GM-CSF overexpression, n = 13). We utilized HCC cells to establish orthotopic transplantation tumor models of HCC with normal and over-expressing GM-CSF. Liver injury, immune inflammatory function and intestinal barrier function were evaluated. The fecal microbiome and metabolome were studied using 16S rRNA absolute quantification sequencing and gas chromatography-mass spectrometry.<br><br>RESULTS: GM-CSF overexpression significantly affected the gut microbiome of mice with HCC and resulted in a high abundance of organisms of the genera Roseburia, Blautia and Butyricimonass, along with a significant reduction in Prevotella, Parabacteroides, Anaerotruncus, Streptococcus, Clostridium, and Mucispirillum. Likewise, GM-CSF overexpression resulted in a substantial increase in fecal biotin and oleic acid levels, along with a prominent decrease in the fecal succinic acid, adenosine, fumaric acid, lipoic acid, and maleic acid levels. Correlation analysis revealed that the intestinal microbiota and fecal metabolites induced by GM-CSF were primarily involved in pathways related to reducing the inflammatory response, biotin metabolism, and intestinal barrier dysfunction.<br><br>CONCLUSION: GM-CSF can protect against HCC development by regulating immunity and modulating the abundance of specific intestinal microorganisms and their metabolites. This study provides new insights into the therapeutic approaches for HCC.}, }
@article {pmid33023268, year = {2020}, author = {Qureshi, F and Adams, J and Hanagan, K and Kang, DW and Krajmalnik-Brown, R and Hahn, J}, title = {Multivariate Analysis of Fecal Metabolites from Children with Autism Spectrum Disorder and Gastrointestinal Symptoms before and after Microbiota Transfer Therapy.}, journal = {Journal of personalized medicine}, volume = {10}, number = {4}, pages = {}, pmid = {33023268}, issn = {2075-4426}, support = {1R01AI110642/NH/NIH HHS/United States ; }, abstract = {Fecal microbiota transplant (FMT) holds significant promise for patients with Autism Spectrum Disorder (ASD) and gastrointestinal (GI) symptoms. Prior work has demonstrated that plasma metabolite profiles of children with ASD become more similar to those of their typically developing (TD) peers following this treatment. This work measures the concentration of 669 biochemical compounds in feces of a cohort of 18 ASD and 20 TD children using ultrahigh performance liquid chromatography-tandem mass spectroscopy. Subsequent measurements were taken from the ASD cohort over the course of 10-week Microbiota Transfer Therapy (MTT) and 8 weeks after completion of this treatment. Univariate and multivariate statistical analysis techniques were used to characterize differences in metabolites before, during, and after treatment. Using Fisher Discriminant Analysis (FDA), it was possible to attain multivariate metabolite models capable of achieving a sensitivity of 94% and a specificity of 95% after cross-validation. Observations made following MTT indicate that the fecal metabolite profiles become more like those of the TD cohort. There was an 82-88% decrease in the median difference of the ASD and TD group for the panel metabolites, and among the top fifty most discriminating individual metabolites, 96% report more comparable values following treatment. Thus, these findings are similar, although less pronounced, as those determined using plasma metabolites.}, }
@article {pmid33022904, year = {2021}, author = {Jung, CY and Bae, JM}, title = {Pathophysiology and protective approaches of gut injury in critical illness.}, journal = {Yeungnam University journal of medicine}, volume = {38}, number = {1}, pages = {27-33}, pmid = {33022904}, issn = {2384-0293}, abstract = {The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.}, }
@article {pmid33022571, year = {2021}, author = {Yu, X and Lv, K and Guan, S and Zhang, X and Sun, L}, title = {Long-term exposure to phenanthrene at environmental-level induces intestinal dysbiosis and disrupted hepatic lipid metabolism in mice.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {268}, number = {Pt B}, pages = {115738}, doi = {10.1016/j.envpol.2020.115738}, pmid = {33022571}, issn = {1873-6424}, mesh = {Animals ; Dysbiosis/chemically induced ; *Gastrointestinal Microbiome ; Lipid Metabolism ; Liver/metabolism ; Male ; Mice ; *Phenanthrenes/metabolism/toxicity ; }, abstract = {Phenanthrene (Phe), among the most ubiquitous polycyclic aromatic hydrocarbons (PAHs) existing in nature and foodstuffs, has severe effects on hepatic lipids metabolism. However, the detailed mechanism involved is still unknown. For environmental chemicals can disturb intestinal microbiota, which plays a vital role in lipids metabolism, we hypothesized that oral exposure to Phe may disrupt the intestinal microbiota, leading to the induction of an abnormal inflammatory response and lipid metabolism dysfunction. Herein, male mice were orally exposed to Phe (0.05, 0.5 and 5 mg/kg/2d) for ten weeks and the results showed that long term exposure to Phe induced significant alteration in relative Bacteroidetes, Firmicutes and Proteobacteria abundance in male mice. Histopathological anomalies, and significantly increased hepatic levels of free fatty acid, cholesterol and triglyceride were observed as well. The expression of hepatic proteins linked to lipid metabolism including peroxisome proliferator-activated receptors (PPARs), liver X receptor β (LXRβ) and retinoid X receptors (RXRs) were upregulated. The importance of the gut microbiota in Phe-altered lipid metabolism disorder was further confirmed by fecal microbiota transplantation (FMT). FMT intervention boosted microbial diversity and attenuated Phe-induced elevation in liver somatic index and hepatic total lipids levels. These results demonstrated that environmental-level Phe altered the composition of gastrointestinal bacteria and subsequently induced hepatic lipid metabolism disorder. These results would be helpful for understanding the health risk posed by Phe.}, }
@article {pmid33022055, year = {2021}, author = {Aloi, M and Bramuzzo, M and Norsa, L and Arrigo, S and Distante, M and Miele, E and Romano, C and Giobbi, C and Panceri, R and Cucchiara, S and Alvisi, P and , }, title = {Disease Activity Patterns in the First 5 Years After Diagnosis in Children With Ulcerative Colitis: A Population-Based Study.}, journal = {Journal of Crohn's &amp; colitis}, volume = {15}, number = {3}, pages = {367-374}, doi = {10.1093/ecco-jcc/jjaa203}, pmid = {33022055}, issn = {1876-4479}, mesh = {Adolescent ; Child ; Colectomy/statistics &amp; numerical data ; Colitis, Ulcerative/*epidemiology/therapy ; Disease Progression ; Drug Utilization/trends ; Female ; Follow-Up Studies ; Glucocorticoids/therapeutic use ; Humans ; Italy/epidemiology ; Male ; Registries ; Remission Induction ; *Severity of Illness Index ; }, abstract = {BACKGROUND: The aim of this study was to define clusters of activity in a population-based cohort during the first 5 years after diagnosis in children with ulcerative colitis [UC] and to identify early prognostic risk factors.<br><br>METHODS: All UC patients from the SIGENP IBD registry with a complete follow-up of at least 5 years were included. Active disease was defined every 6 months in the presence of at least one of the following: clinical activity [Paediatric Ulcerative Colitis Activity Index &#x2265;&#x2005;35]; endoscopic activity [Mayo score&#x2005;&#x2265;&#x2005;1]; faecal calprotectin&#x2005;>&#x2005;250 &#xb5;g/g; hospitalization; surgery; or treatment escalation. Formula-based clusters were generated based on four published questionnaire-based activity patterns in adults, plus one additional cluster.<br><br>RESULTS: In total, 226 patients were identified. Forty-two [19%] had moderate-severe chronically active disease, 31 [14%] chronic-intermittent, 75 [33%] quiescent, 54 [24%] active disease in the first 2 years after the diagnosis, then sustained remission, and 24 [11%] a remission in the first 2 years then an active disease. Mild disease onset along with a lower clinical severity not requiring the use of corticosteroids at 6 months were related to a quiescent disease course at the next follow-up (logistic model area under the curve 0.86 [95% confidence interval 0.78-0.94]; positive predictive value 67%; negative predictive value 70%). Eight per cent of patients needed surgery, none in the quiescent group [p&#x2005;=&#x2005;0.04].<br><br>CONCLUSIONS: More than one-third of children with UC present with a chronically active or intermittent course during the first 5 years of follow-up. A significant group of patients has active disease in the first 2 years and then sustained remission. Interestingly, after initial treatment, one-third of patients have well-controlled disease throughout.}, }
@article {pmid33020290, year = {2020}, author = {Bonomo, RR and Cook, TM and Gavini, CK and White, CR and Jones, JR and Bovo, E and Zima, AV and Brown, IA and Dugas, LR and Zakharian, E and Aubert, G and Alonzo, F and Calcutt, NA and Mansuy-Aubert, V}, title = {Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {42}, pages = {26482-26493}, pmid = {33020290}, issn = {1091-6490}, support = {K08 HL145136/HL/NHLBI NIH HHS/United States ; R01 DK111848/DK/NIDDK NIH HHS/United States ; R01 DK117404/DK/NIDDK NIH HHS/United States ; R01 HL130231/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Butyrates/metabolism ; Diet, High-Fat ; Diet, Western ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/drug effects ; Gene Expression ; Insulin Resistance ; Lipid Metabolism/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Microbiota ; Neuralgia/metabolism ; Obesity/*microbiology/physiopathology ; Peripheral Nervous System/metabolism/physiology ; Peripheral Nervous System Diseases/*therapy ; }, abstract = {Obesity affects over 2 billion people worldwide and is accompanied by peripheral neuropathy (PN) and an associated poorer quality of life. Despite high prevalence, the molecular mechanisms underlying the painful manifestations of PN are poorly understood, and therapies are restricted to use of painkillers or other drugs that do not address the underlying disease. Studies have demonstrated that the gut microbiome is linked to metabolic health and its alteration is associated with many diseases, including obesity. Pathologic changes to the gut microbiome have recently been linked to somatosensory pain, but any relationships between gut microbiome and PN in obesity have yet to be explored. Our data show that mice fed a Western diet developed indices of PN that were attenuated by concurrent fecal microbiome transplantation (FMT). In addition, we observed changes in expression of genes involved in lipid metabolism and calcium handling in cells of the peripheral nerve system (PNS). FMT also induced changes in the immune cell populations of the PNS. There was a correlation between an increase in the circulating short-chain fatty acid butyrate and pain improvement following FMT. Additionally, butyrate modulated gene expression and immune cells in the PNS. Circulating butyrate was also negatively correlated with distal pain in 29 participants with varied body mass index. Our data suggest that the metabolite butyrate, secreted by the gut microbiome, underlies some of the effects of FMT. Targeting the gut microbiome, butyrate, and its consequences may represent novel viable approaches to prevent or relieve obesity-associated neuropathies.}, }
@article {pmid33013647, year = {2020}, author = {Engen, PA and Zaferiou, A and Rasmussen, H and Naqib, A and Green, SJ and Fogg, LF and Forsyth, CB and Raeisi, S and Hamaker, B and Keshavarzian, A}, title = {Single-Arm, Non-randomized, Time Series, Single-Subject Study of Fecal Microbiota Transplantation in Multiple Sclerosis.}, journal = {Frontiers in neurology}, volume = {11}, number = {}, pages = {978}, pmid = {33013647}, issn = {1664-2295}, abstract = {Emerging evidence suggests intestinal microbiota as a central contributing factor to the pathogenesis of Relapsing-Remitting-Multiple-Sclerosis (RRMS). This novel RRMS study evaluated the impact of fecal-microbiota-transplantation (FMT) on a broad array of physiological/clinical outcomes using deep metagenome sequencing of fecal microbiome. FMT interventions were associated with increased abundances of putative beneficial stool bacteria and short-chain-fatty-acid metabolites, which were associated with increased/improved serum brain-derived-neurotrophic-factor levels and gait/walking metrics. This proof-of-concept single-subject longitudinal study provides evidence of potential importance of intestinal microbiota in the pathogenesis of MS, and scientific rationale to help design future randomized controlled trials assessing FMT in RRMS patients.}, }
@article {pmid33011173, year = {2021}, author = {Kelly, CR and Yen, EF and Grinspan, AM and Kahn, SA and Atreja, A and Lewis, JD and Moore, TA and Rubin, DT and Kim, AM and Serra, S and Nersesova, Y and Fredell, L and Hunsicker, D and McDonald, D and Knight, R and Allegretti, JR and Pekow, J and Absah, I and Hsu, R and Vincent, J and Khanna, S and Tangen, L and Crawford, CV and Mattar, MC and Chen, LA and Fischer, M and Arsenescu, RI and Feuerstadt, P and Goldstein, J and Kerman, D and Ehrlich, AC and Wu, GD and Laine, L}, title = {Fecal Microbiota Transplantation Is Highly Effective in Real-World Practice: Initial Results From the FMT National Registry.}, journal = {Gastroenterology}, volume = {160}, number = {1}, pages = {183-192.e3}, pmid = {33011173}, issn = {1528-0012}, support = {K23 DK119544/DK/NIDDK NIH HHS/United States ; P30 DK042086/DK/NIDDK NIH HHS/United States ; R24 AI118629/AI/NIAID NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*therapy ; Irritable Bowel Syndrome/*therapy ; Middle Aged ; Prospective Studies ; *Registries ; Treatment Outcome ; United States ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is used commonly for treatment of Clostridioides difficile infections (CDIs), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers.<br><br>METHODS: Patients undergoing FMT in clinical practices across North America were eligible. Participating investigators enter de-identified data into an online platform, including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes.<br><br>RESULTS: Of the first 259 participants enrolled at 20 sites, 222 had completed short-term follow-up at 1 month and 123 had follow-up to 6 months; 171 (66%) were female. All FMTs were done for CDI and 249 (96%) used an unknown donor (eg, stool bank). One-month cure occurred in 200 patients (90%); of these, 197 (98%) received only 1 FMT. Among 112 patients with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (n&#xa0;= 5 [2%]) and abdominal pain (n&#xa0;= 4 [2%]); 3 patients (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%).<br><br>CONCLUSIONS: This prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT.}, }
@article {pmid33010597, year = {2020}, author = {Zhao, Y and Tang, Y and Chen, L and Lv, S and Liu, S and Nie, P and Aguilar, ZP and Xu, H}, title = {Restraining the TiO2 nanoparticles-induced intestinal inflammation mediated by gut microbiota in juvenile rats via ingestion of Lactobacillus rhamnosus GG.}, journal = {Ecotoxicology and environmental safety}, volume = {206}, number = {}, pages = {111393}, doi = {10.1016/j.ecoenv.2020.111393}, pmid = {33010597}, issn = {1090-2414}, mesh = {Adult ; Animals ; Child ; Feces/chemistry/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Homeostasis ; Humans ; Inflammation ; Intestinal Mucosa/*drug effects/immunology/metabolism/microbiology ; Lacticaseibacillus rhamnosus/*growth &amp; development ; Liver/drug effects/metabolism ; Male ; Nanoparticles/metabolism/*toxicity ; Probiotics/*therapeutic use ; Rats ; Titanium/metabolism/*toxicity ; }, abstract = {Human were given a lot of opportunities to ingest TiO2 NPs in the environment. Children have low, sensitive intestinal tolerance, and they could be exposed to higher levels of TiO2 NPs than adults. Few studies have been conducted on the interaction between TiO2 NPs and juvenile intestine phase models. Thus, in this work, weaning rats were orally exposed to TiO2 NPs for 7 and 14 days. Results indicate that Ti accumulated in the intestine, liver, and feces. Inflammatory infiltration damage was observed in the colonic epithelial tissue, and gut microbiota fluctuated with a decreased abundance of Lactobacilli in feces. Oral supplementation with Lactobacillus rhamnosus GG (LGG) lessened TiO2 NPs-induced colonic inflammatory injury, which might due to downregulation of nuclear factor kappa-B (NF-κB). Meanwhile, LGG maintained normal intestinal microbiome homeostasis, thereby improving TiO2 NPs-induced colon injury in juvenile rats. Moreover, fecal microbiota transplant (FMT) experiment indicated possible TiO2 NPs-induced intestinal microbiota disorder led to colonic inflammation. Our works suggested the urgent need for additional studies on the risk safety assessment, mechanism, and prevention of juvenile health damage from exposure to TiO2 NPs.}, }
@article {pmid33007265, year = {2020}, author = {Korpela, K and Helve, O and Kolho, KL and Saisto, T and Skogberg, K and Dikareva, E and Stefanovic, V and Salonen, A and Andersson, S and de Vos, WM}, title = {Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study.}, journal = {Cell}, volume = {183}, number = {2}, pages = {324-334.e5}, doi = {10.1016/j.cell.2020.08.047}, pmid = {33007265}, issn = {1097-4172}, mesh = {Adult ; Cesarean Section/adverse effects ; Delivery, Obstetric ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Infant ; Infant, Newborn ; Male ; Microbiota/physiology ; Mothers ; Pregnancy ; Proof of Concept Study ; Vagina/microbiology ; }, abstract = {Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a diluted fecal sample from their own mothers, taken 3 weeks prior to delivery. All seven infants had an uneventful clinical course during the 3-month follow-up and showed no adverse effects. The temporal development of the fecal microbiota composition of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clinical and microbiological screening.}, }
@article {pmid33006187, year = {2021}, author = {Hyde, MK and Masser, BM}, title = {Eligible blood donors' decisions about donating stool for fecal microbiota transplantation: Does ambivalence play a role?.}, journal = {Transfusion}, volume = {61}, number = {2}, pages = {474-483}, doi = {10.1111/trf.16109}, pmid = {33006187}, issn = {1537-2995}, support = {//This work was supported by an award made from The University of Queensland (UQ) Vice-Chancellor's Strategic Funds (B.M.M.) and internal funds granted by the UQ School of Psychology (M.K.H.). Australian governments fund Australian Red Cross Lifeblood for the provision of blood, blood products, and services to the Australian community/ ; }, mesh = {Adult ; Altruism ; *Attitude ; Australia ; Blood Donors/*psychology ; Body Mass Index ; Cross-Sectional Studies ; Disgust ; Educational Status ; Fecal Microbiota Transplantation/*psychology ; Feces ; Female ; Humans ; Male ; Middle Aged ; Motivation ; Self Efficacy ; Surveys and Questionnaires ; Volition ; Young Adult ; }, abstract = {UNLABELLED: Blood collection agencies (BCAs) are expanding core business by inviting blood donors to donate stool for fecal microbiota transplantation (FMT). However, whether blood donors also want to donate stool is unclear since, despite its benefits, stool donation is viewed by many as unpleasant. This study examined the prevalence, contributors to, and role of these mixed feelings (ambivalence) in stool donation intentions.<br><br>STUDY DESIGN AND METHODS: This cross-sectional study surveyed Australian residents aged 18&#x2009;years or more who believed themselves eligible to donate blood and met broad criteria for prescreening as a stool donor (eg, healthy, not taking medication). Survey questions assessed attitude, norms, self-efficacy, motives, disgust, ambivalence, and intentions to donate stool.<br><br>RESULTS: A total of 382 eligible blood donors aged not more than 50&#x2009;years (mean, 28.71&#x2009;years; 48% female, 62% "healthy" body mass index) participated. Six percent indicated no ambivalence about donating stool. In regression, significant determinants of ambivalence were less awareness of FMT, lower self-efficacy, motivated by ensuring that stool is available for loved ones, and more disgust about stool donation. Higher ambivalence contributed to decreased donation intention. Self-efficacy and disgust differentiated participants with moderate ambivalence, a group likely responsive to intervention, from those with low or high ambivalence.<br><br>CONCLUSION: Ambivalence about donating stool was common among eligible blood donors. BCAs should raise awareness about stool donation and FMT before requesting donation. BCAs may increase cost savings and donor retention by giving clear guidance about donation requirements and implementing processes that build confidence. Early screening of potential donors for ambivalence and disgust will enable BCAs to provide decision support.}, }
@article {pmid33006061, year = {2021}, author = {Patel, SD and Hung, YC and Hashmi, ZG and Feinman, M and D'Adamo, CR and Svoboda, S and Wolf, JH}, title = {Surgical Management of Diverticulitis-Associated Clostridioides Difficile Infection.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {25}, number = {3}, pages = {829-830}, pmid = {33006061}, issn = {1873-4626}, mesh = {Clostridioides ; *Clostridium Infections/complications/diagnosis ; *Diverticulitis/complications/surgery ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid33004548, year = {2021}, author = {Wrzosek, L and Ciocan, D and Hugot, C and Spatz, M and Dupeux, M and Houron, C and Lievin-Le Moal, V and Puchois, V and Ferrere, G and Trainel, N and Mercier-Nomé, F and Durand, S and Kroemer, G and Voican, CS and Emond, P and Straube, M and Sokol, H and Perlemuter, G and Cassard, AM}, title = {Microbiota tryptophan metabolism induces aryl hydrocarbon receptor activation and improves alcohol-induced liver injury.}, journal = {Gut}, volume = {70}, number = {7}, pages = {1299-1308}, doi = {10.1136/gutjnl-2020-321565}, pmid = {33004548}, issn = {1468-3288}, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/agonists/genetics/*metabolism ; Carbazoles/pharmacology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/chemistry ; Female ; Humans ; Intestines/*microbiology/physiopathology ; Liver Diseases, Alcoholic/drug therapy/*etiology/metabolism ; Metabolome/drug effects ; Mice ; Mice, Knockout ; Microbiota/drug effects/*physiology ; Pectins/*pharmacology/therapeutic use ; Prebiotics ; Receptors, Aryl Hydrocarbon/agonists/genetics/*metabolism ; Tryptophan/*metabolism ; }, abstract = {OBJECTIVE: Chronic alcohol consumption is an important cause of liver-related deaths. Specific intestinal microbiota profiles are associated with susceptibility or resistance to alcoholic liver disease in both mice and humans. We aimed to identify the mechanisms by which targeting intestinal microbiota can improve alcohol-induced liver lesions.<br><br>DESIGN: We used human associated mice, a mouse model of alcoholic liver disease transplanted with the intestinal microbiota of alcoholic patients and used the prebiotic, pectin, to modulate the intestinal microbiota. Based on metabolomic analyses, we focused on microbiota tryptophan metabolites, which are ligands of the aryl hydrocarbon receptor (AhR). Involvement of the AhR pathway was assessed using both a pharmacological approach and AhR-deficient mice.<br><br>RESULTS: Pectin treatment modified the microbiome and metabolome in human microbiota-associated alcohol-fed mice, leading to a specific faecal signature. High production of bacterial tryptophan metabolites was associated with an improvement of liver injury. The AhR agonist Ficz (6-formylindolo (3,2-b) carbazole) reduced liver lesions, similarly to prebiotic treatment. Conversely, inactivation of the ahr gene in alcohol-fed AhR knock-out mice abrogated the beneficial effects of the prebiotic. Importantly, patients with severe alcoholic hepatitis have low levels of bacterial tryptophan derivatives that are AhR agonists.<br><br>CONCLUSIONS: Improvement of alcoholic liver disease by targeting the intestinal microbiota involves the AhR pathway, which should be considered as a new therapeutic target.}, }
@article {pmid33004295, year = {2020}, author = {Ianiro, G and Bibbò, S and Masucci, L and Quaranta, G and Porcari, S and Settanni, CR and Lopetuso, LR and Fantoni, M and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Maintaining standard volumes, efficacy and safety, of fecal microbiota transplantation for C. difficile infection during the COVID-19 pandemic: A prospective cohort study.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {52}, number = {12}, pages = {1390-1395}, pmid = {33004295}, issn = {1878-3562}, mesh = {Adult ; Aged ; Aged, 80 and over ; COVID-19/diagnosis/*prevention &amp; control/transmission ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Cohort Studies ; Delivery of Health Care/*methods ; Donor Selection ; Fecal Microbiota Transplantation/*methods ; Feces/virology ; Female ; *Gastroenterology ; Humans ; Infection Control/methods ; Italy ; Male ; Middle Aged ; Patient Selection ; Prospective Studies ; Quarantine ; Recurrence ; Specimen Handling/methods ; Workflow ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) can be a life-saving treatment against recurrent Clostridioides difficile infection (CDI). It is therefore necessary to maintain this procedure available for these patients during the COVID-19 pandemic while keeping high efficacy and safety standards.<br><br>AIMS: To report outcomes of a FMT service that has adapted its operational workflow during COVID-19 pandemic to continue offering FMT to patients with CDI.<br><br>METHODS: All patients with CDI referred to our center for FMT during pandemic were prospectively included. Each step of the FMT working protocol was adapted with specific security measures to prevent the transmission of SARS-CoV-2.<br><br>RESULTS: Of 26 patients evaluated for FMT, 21 were treated for recurrent or refractory CDI. Eighteen patients completed the 8-week follow-up, and no one recurred after FMT. Follow-up is ongoing in 3 patients, although in all of them diarrhea disappeared after the first procedure. No serious adverse events were reported. Two patients had also COVID-19-related pneumonia, and were cured both from CDI and COVID-19.<br><br>CONCLUSION: This is the first report to show that it is possible to maintain standard volumes, efficacy and safety of FMT for recurrent CDI during the COVID-19 pandemic, by adopting specific changes in the operational workflow.}, }
@article {pmid33004079, year = {2020}, author = {D'Amato, A and Di Cesare Mannelli, L and Lucarini, E and Man, AL and Le Gall, G and Branca, JJV and Ghelardini, C and Amedei, A and Bertelli, E and Regoli, M and Pacini, A and Luciani, G and Gallina, P and Altera, A and Narbad, A and Gulisano, M and Hoyles, L and Vauzour, D and Nicoletti, C}, title = {Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {140}, pmid = {33004079}, issn = {2049-2618}, support = {BBS/E/F/00044453/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J004529/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/L01632X/1/MRC_/Medical Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10355/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Aging/*physiology ; Animals ; *Fecal Microbiota Transplantation ; Hippocampus/*physiology ; Male ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; *Neuronal Plasticity ; Quality of Life ; Spatial Learning/*physiology ; *Synaptic Transmission ; }, abstract = {BACKGROUND: The gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems; however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients altered the hippocampus, an area of the central nervous system (CNS) known to be affected by the ageing process and related functions.<br><br>RESULTS: Young adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. We report that FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (Lachnospiraceae, Faecalibaculum, and Ruminococcaceae) and disorders of the CNS (Prevotellaceae and Ruminococcaceae) was observed. Finally, the detrimental effect of FMT from aged donors on the CNS was confirmed by the observation that microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype; on the contrary, gut permeability and levels of systemic and local (hippocampus) cytokines were not affected.<br><br>CONCLUSION: These results demonstrate that age-associated shifts of the microbiota have an impact on protein expression and key functions of the CNS. Furthermore, these results highlight the paramount importance of the gut-brain axis in ageing and provide a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions and the declining quality of life in the elderly. Video Abstract.}, }
@article {pmid33003421, year = {2020}, author = {Heimesaat, MM and Genger, C and Klove, S and Weschka, D and Mousavi, S and Bereswill, S}, title = {The Host-Specific Intestinal Microbiota Composition Impacts Campylobacter coli Infection in a Clinical Mouse Model of Campylobacteriosis.}, journal = {Pathogens (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {33003421}, issn = {2076-0817}, support = {Zoonoses research consortium PAC-Campylobacter (IP7/ 01KI1725D)//Bundesministerium f&#xfc;r Bildung, Wissenschaft, Forschung und Technologie/ ; ZIM: ZF4117904 AJ8//Bundesministerium f&#xfc;r Wirtschaft und Energie/ ; }, abstract = {Human Campylobacter-infections are progressively rising globally. However, the molecular mechanisms underlying C. coli-host interactions are incompletely understood. In this study, we surveyed the impact of the host-specific intestinal microbiota composition during peroral C. coli infection applying an established murine campylobacteriosis model. Therefore, microbiota-depleted IL-10[-/-] mice were subjected to peroral fecal microbiota transplantation from murine versus human donors and infected with C. coli one week later by gavage. Irrespective of the microbiota, C. coli stably colonized the murine gastrointestinal tract until day 21 post-infection. Throughout the survey, C. coli-infected mice with a human intestinal microbiota displayed more frequently fecal blood as their murine counterparts. Intestinal inflammatory sequelae of C. coli-infection could exclusively be observed in mice with a human intestinal microbiota, as indicated by increased colonic numbers of apoptotic epithelial cells and innate as well as adaptive immune cell subsets, which were accompanied by more pronounced pro-inflammatory cytokine secretion in the colon and mesenteric lymph nodes versus mock controls. However, in extra-intestinal, including systemic compartments, pro-inflammatory responses upon pathogen challenge could be assessed in mice with either microbiota. In conclusion, the host-specific intestinal microbiota composition has a profound effect on intestinal and systemic pro-inflammatory immune responses during C. coli infection.}, }
@article {pmid33003084, year = {2020}, author = {Lindner, S and Peled, JU}, title = {Update in clinical and mouse microbiota research in allogeneic haematopoietic cell transplantation.}, journal = {Current opinion in hematology}, volume = {27}, number = {6}, pages = {360-367}, pmid = {33003084}, issn = {1531-7048}, support = {K08 HL143189/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Enterococcus/isolation &amp; purification ; Feces/microbiology ; Graft vs Host Disease/etiology/*microbiology/mortality/pathology ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods/mortality ; Humans ; Mice ; *Microbiota ; Transplantation, Homologous/adverse effects/methods/mortality ; }, abstract = {PURPOSE OF REVIEW: The intestinal microbiota plays a critical role in intestinal homeostasis and immune regulation and has been recognized as a predictor of clinical outcome in patients undergoing allogeneic haematopoietic cell transplantation (allo-HCT) and specifically a determinant of the severity of graft-versus-host disease (GVHD) in mouse models. As GVHD is the most important cause of nonrelapse mortality (NRM) after allo-HCT, understanding the mechanisms by which modifying the microbiota may prevent or decrease the severity of GVHD would represent an important advance.<br><br>RECENT FINDINGS: Microbiota injury was observed globally and higher diversity at peri-engraftment was associated with lower mortality. Lactose is a dietary factor that promotes post-allo-HCT Enterococcus expansion, which is itself associated with mortality from GVHD in patients and exacerbates GVHD in mice. Bacterial and fungal bloodstream infections are preceded by intestinal colonization with a corresponding organism, supporting the gut as a source for many bloodstream infections. Metabolomic profiling studies showed that GVHD is associated with changes in faecal and plasma microbiota-derived molecules.<br><br>SUMMARY: In this review, we highlight some of the most recent and important findings in clinical and mouse microbiota research, as it relates to allo-HCT. Many of these are already being translated into clinical trials that have the potential to change future practice in the care of patients.}, }
@article {pmid33002829, year = {2020}, author = {Fan, Q and Guan, X and Hou, Y and Liu, Y and Wei, W and Cai, X and Zhang, Y and Wang, G and Zheng, X and Hao, H}, title = {Paeoniflorin modulates gut microbial production of indole-3-lactate and epithelial autophagy to alleviate colitis in mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {79}, number = {}, pages = {153345}, doi = {10.1016/j.phymed.2020.153345}, pmid = {33002829}, issn = {1618-095X}, mesh = {Animals ; Autophagy/drug effects ; Bridged-Ring Compounds/pharmacology ; Colitis/chemically induced/*drug therapy/*microbiology ; Drugs, Chinese Herbal/pharmacology ; Dysbiosis/drug therapy/microbiology ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/physiology ; Glucosides/immunology/*pharmacology ; HCT116 Cells ; Humans ; Immunologic Factors/pharmacology ; Indoles/*metabolism ; Male ; Mice, Inbred BALB C ; Monoterpenes/*pharmacology ; Paeonia/chemistry ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Total glucosides of peony (TGP), extracted from the root and rhizome of Paeonia lactiflora Pall, has well-confirmed immunomodulatory efficacy in the clinic. However, the mechanism and active ingredients remain largely unclear.<br><br>HYPOTHESIS/PURPOSE: Our previous study revealed a low systemic exposure but predominant gut distribution of TGP components. The aim of this study was to investigate involvement of the gut microbiota in the immunoregulatory effects and identify the active component.<br><br>METHODS: Mice received 3% DSS to establish a model of colitis. The treatment group received TGP or single paeoniflorin (PF) or albiflorin (AF). Body weight, colon length, inflammatory and histological changes were assessed. Gut microbiota structure was profiled by 16s rRNA sequencing. Antibiotic treatment and fecal transplantation were used to explore the involvement of gut microbiota. Metabolomic assay of host and microbial metabolites in colon was performed.<br><br>RESULTS: TGP improved colonic injury and gut microbial dysbiosis in colitis mice, and PF was responsible for the protective effects. Fecal microbiota transfer from TGP-treated mice conferred resilience to colitis, while antibiotic treatment abrogated the protective effects. Both TGP and PF decreased colonic indole-3-lactate (ILA), a microbial tryptophan metabolite. ILA was further identified as an inhibitor of epithelial autophagy and ILA supplementation compromised the benefits of TGP.<br><br>CONCLUSION: Our findings suggest that TGP acts in part through a gut microbiota-ILA-epithelial autophagy axis to alleviate colitis.}, }
@article {pmid32999906, year = {2020}, author = {Ortigão, R and Pimentel-Nunes, P and Dinis-Ribeiro, M and Libânio, D}, title = {Gastrointestinal Microbiome - What We Need to Know in Clinical Practice.}, journal = {GE Portuguese journal of gastroenterology}, volume = {27}, number = {5}, pages = {336-351}, pmid = {32999906}, issn = {2341-4545}, abstract = {Human gut microbiota plays an important role in individual health. When the balance between host and gut microbiota is disrupted, changes in microbiota composition and function occur, which is referred as dysbiosis. Environmental factors as diet, proton pump inhibitors, and antibiotics can lead to a permanent dysbiotic disruption. Clarification of these imbalances was made possible by recent advances in genome sequencing methods that supported acknowledgment of the interplay between microbiome and intestinal and extraintestinal disorders. This review focuses on the microbiota impact in inflammatory bowel disease, gastric cancer, colorectal cancer, nonalcoholic fatty liver disease (NAFLD), irritable bowel syndrome (IBS), and Clostridium difficile infection (CDI). Furthermore, novel therapies are summarized. Fecal microbiota transplant (FMT) is a successful and established therapy in recurrent CDI, and its application in other dysbiosis-related diseases is attracting enormous interest. Pre- and probiotics target microbial rebalance and have positive effects mainly in NAFLD, ulcerative colitis, IBS, and CDI patients. Promising anticarcinogenic effects have also been demonstrated in animal models. The literature increasingly describes microbial changes in many dysbiotic disorders and shows what needs to be treated. However, probiotics and FMT application in clinical practice suffers from a shortage of randomized controlled trials with standardized therapy regimens to support their recommendation.}, }
@article {pmid32993381, year = {2020}, author = {Li, Q and Guo, L and Wang, L and Miao, J and Cui, H and Li, L and Geng, K and Zhao, L and Sun, X and Jia, J and Bian, Y}, title = {Composition of "gold juice" using an ancient method based on intestinal microecology.}, journal = {The Journal of international medical research}, volume = {48}, number = {9}, pages = {300060520931288}, pmid = {32993381}, issn = {1473-2300}, mesh = {Child ; Child, Preschool ; Fecal Microbiota Transplantation ; Feces ; Female ; *Gastrointestinal Microbiome ; *Gold ; Humans ; Male ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVE: To identify potentially effective bacterial components of gold juice, a traditional Chinese medicine treatment used for fecal microbiota transplantation.<br><br>METHODS: Fecal samples were collected from five healthy children (two boys and three girls; mean age, 7.52&#x2009;&#xb1;&#x2009;2.31 years). The children had no history of antibiotic use or intestinal microecological preparation in the preceding 3 months. Fresh fecal samples were collected from children to prepare gold juice in mid-to-late November, in accordance with traditional Chinese medicine methods, then used within 7 days. Finally, 16S rDNA sequence analysis was used to identify potentially effective bacterial components of gold juice. QIIME software was used for comparisons of microbial species among gold juice, diluent, filtrate, and loess samples.<br><br>RESULTS: Microflora of gold juice exhibited considerable changes following "ancient method" processing. Microbial components significantly differed between gold juice and filtrate samples. The gold juice analyzed in our study consisted of microbes that synthesize carbohydrates and amino acids by degrading substances, whereas the filtrate contained probiotic flora, Bacteroides, and Prevotella 9.<br><br>CONCLUSIONS: This study of microbial components in gold juice and filtrate provided evidence regarding effective bacterial components in gold juice, which may aid in clinical decisions concerning fecal microbiota transplantation.}, }
@article {pmid32992653, year = {2020}, author = {Quagliariello, A and Del Chierico, F and Reddel, S and Russo, A and Onetti Muda, A and D'Argenio, P and Angelino, G and Romeo, EF and Dall'Oglio, L and De Angelis, P and Putignani, L and All The Other Fmt Opbg Committee Collaborators, }, title = {Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations.}, journal = {Microorganisms}, volume = {8}, number = {10}, pages = {}, pmid = {32992653}, issn = {2076-2607}, support = {201702P003961//Ministero della Salute/ ; 201802G004314//MINISTERO DELLA SALUTE/ ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts' time-point profiles, donors and control cohorts' baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient's condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.}, }
@article {pmid32991940, year = {2020}, author = {Navalkele, BD and Polistico, J and Sandhu, A and Awali, R and Krishna, A and Chandramohan, S and Tillotson, G and Chopra, T}, title = {Clinical outcomes after faecal microbiota transplant by retention enema in both immunocompetent and immunocompromised patients with recurrent Clostridioides difficile infections at an academic medical centre.}, journal = {The Journal of hospital infection}, volume = {106}, number = {4}, pages = {643-648}, doi = {10.1016/j.jhin.2020.09.027}, pmid = {32991940}, issn = {1532-2939}, mesh = {Academic Medical Centers ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Enema ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Immunocompromised Host ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (CDI) is one of the most common and challenging infections to treat in healthcare facilities. Faecal microbiota transplantation (FMT) is recommended as a definitive treatment option.<br><br>METHODS: We performed a retrospective review of 50 patients from January 2015 to December 2019 who underwent FMT for recurrent CDI. Primary outcome was recurrence of CDI within 12-weeks of FMT and secondary outcomes were the need for repeat FMT, serious adverse outcomes related to FMT and all-cause mortality.<br><br>RESULTS: Fifty charts were reviewed, of which 47 cases comprising 17 immunocompromised patients treated with FMT via retention enema were included in the study. The majority of the patients had &#x2265;3 recurrent CDIs (62%). Nine (19%) patients failed to respond to the first FMT and five underwent repeat FMT within four to 12 weeks. The cure rate was 81% after the first FMT (38/47) and 91% after the second FMT treatment (43/47). Serious adverse events occurred in 2% and all-cause mortality was 2% at 90-day follow up.<br><br>CONCLUSION: Our study demonstrated the safety and efficacy of FMT administered via retention enema, a simple bedside procedure, for the treatment and prevention of recurrent non-severe and severe CDI with an overall cure rate of 91%.}, }
@article {pmid32991818, year = {2020}, author = {Goll, R and Johnsen, PH and Hjerde, E and Diab, J and Valle, PC and Hilpusch, F and Cavanagh, JP}, title = {Effects of fecal microbiota transplantation in subjects with irritable bowel syndrome are mirrored by changes in gut microbiome.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1794263}, pmid = {32991818}, issn = {1949-0984}, mesh = {Adult ; Aged ; Bacteria/classification/genetics/growth &amp; development/metabolism ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*microbiology/*therapy ; Male ; Middle Aged ; Tissue Donors ; Treatment Outcome ; Young Adult ; }, abstract = {Irritable bowel syndrome (IBS) is a common disorder of the lower gastrointestinal tract. The pathophysiology is far from settled, but a gut microbial dysbiosis is hypothesized to be a contributing factor. We earlier published a randomized double-blind placebo-controlled clinical trial on fecal microbiota transplantation (FMT) for IBS - the REFIT trial. The present data set describes the engraftment and includes participants from the study who received active FMT; 14 participants with effect of FMT (Effect) and 8 without (No effect). Samples were collected at baseline, after 6 and 12 months. Samples from the transplants (Donor) served as a comparator. In total 66 recipient samples and 17 donor samples were subjected to deep metagenomic sequencing, and taxonomic and functional analyses were performed. Alpha diversity measures showed a significantly increased diversity and evenness in the IBS groups compared to the donors. Taxonomic profiles showed higher relative abundance of phylum Firmicutes, and lower relative abundance of phylum Bacteroidetes, compared to donors at baseline. This profile was shifted toward the donor profile following FMT. Imputed growth rates showed that the resulting growth pattern was a conglomerate of donor and recipient activity. Thirty-four functional subclasses showed distinct differences between baseline samples and donors, most of which were shifted toward a donor-like profile after FMT. All of these changes were less pronounced in the No effect group. We conclude that FMT induces long-term changes in gut microbiota, and these changes mirror the clinical effect of the treatment. The study was registered in ClinicalTrials.gov (NCT02154867).}, }
@article {pmid32991720, year = {2020}, author = {Yoshifuji, K and Inamoto, K and Kiridoshi, Y and Takeshita, K and Sasajima, S and Shiraishi, Y and Yamashita, Y and Nisaka, Y and Ogura, Y and Takeuchi, R and Toya, T and Igarashi, A and Najima, Y and Doki, N and Kobayashi, T and Ohashi, K and Suda, W and Atarashi, K and Shiota, A and Hattori, M and Honda, K and Kakihana, K}, title = {Prebiotics protect against acute graft-versus-host disease and preserve the gut microbiota in stem cell transplantation.}, journal = {Blood advances}, volume = {4}, number = {19}, pages = {4607-4617}, pmid = {32991720}, issn = {2473-9537}, mesh = {*Gastrointestinal Microbiome ; *Graft vs Host Disease/prevention &amp; control ; *Hematopoietic Stem Cell Transplantation ; Humans ; Prebiotics ; Prospective Studies ; }, abstract = {Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, management of aGVHD is important for successful transplantation. Mucosal damage and alteration of the gut microbiota after allo-HSCT are key factors in the development of aGVHD. We conducted a prospective study to evaluate the ability of prebiotics, which can alleviate mucosal damage and manipulate the gut microbiota, to mitigate posttransplantation complications, including aGVHD. Resistant starch (RS) and a commercially available prebiotics mixture, GFO, were administered to allo-HSCT recipients from pretransplantation conditioning to day 28 after allo-HSCT. Prebiotic intake mitigated mucosal injury and reduced the incidence of all aGVHD grades combined and of aGVHD grades 2 to 4. The cumulative incidence of skin aGVHD was markedly decreased by prebiotics intake. Furthermore, the gut microbial diversity was well maintained and butyrate-producing bacterial population were preserved by prebiotics intake. In addition, the posttransplantation fecal butyrate concentration was maintained or increased more frequently in the prebiotics group. These observations indicate that prebiotic intake may be an effective strategy for preventing aGVHD in allo-HSCT, thereby improving treatment outcomes and the clinical utility of stem cell transplantation approaches. This study was registered on the University Hospital Medical Information Network (UMIN) clinical trials registry (https://www.umin.ac.jp/ctr/index.htm) as #UMIN000027563.}, }
@article {pmid32991697, year = {2021}, author = {Khanna, S and Kraft, CS}, title = {Fecal Microbiota Transplantation: Tales of Caution.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {72}, number = {11}, pages = {e881-e882}, doi = {10.1093/cid/ciaa1492}, pmid = {32991697}, issn = {1537-6591}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid32991434, year = {2020}, author = {Zheng, YM and He, XX and Xia, HH and Yuan, Y and Xie, WR and Cai, JY and Xu, JT and Wu, LH}, title = {Multi-donor multi-course faecal microbiota transplantation relieves the symptoms of chronic hemorrhagic radiation proctitis: A case report.}, journal = {Medicine}, volume = {99}, number = {39}, pages = {e22298}, pmid = {32991434}, issn = {1536-5964}, mesh = {Aftercare ; Chronic Disease ; Colonoscopy/methods ; Diarrhea/etiology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Hemorrhage/*therapy ; Humans ; Magnetic Resonance Imaging/methods ; Middle Aged ; Proctitis/diagnosis/*etiology/pathology ; RNA, Ribosomal, 16S/genetics ; Radiation Injuries/*complications/diagnostic imaging/pathology ; Tissue Donors ; Treatment Outcome ; }, abstract = {RATIONALE: There are many treatments for chronic hemorrhagic radiation colorectal inflammation, but only a few treatments are supported by high-quality research evidence. Studies have shown that the occurrence and development of radiation proctitis are closely associated with the intestinal flora. Animal studies have indicated that faecal microbiota transplantation (FMT) can improve radiation enteropathy in a mouse model.<br><br>PATIENT CONCERNS: A 45-year-old female patient suffered from recurrent hematochezia and diarrhea for half a year after radiotherapy and underwent recurrent transfusion treatments. Colonoscopy showed obvious congestion of the sigmoid colon and rectal mucosa, a smooth surface, and bleeding that was easily induced by touch, which are consistent with radiation proctitis. The pathological findings revealed chronic mucosal inflammation. The magnetic resonance imaging examination of the pelvic cavity with a plain scan and enhancement showed changes after radiotherapy and chemotherapy, and no obvious tumor recurrence or metastasis was found. The laboratory examinations excluded pathogen infection.<br><br>DIAGNOSES: Based on the history and examinations, the final diagnosis of this patient was chronic hemorrhagic radiation proctitis.<br><br>INTERVENTIONS: The patient was treated with a total of 4 individual courses of FMT.<br><br>OUTCOMES: After the six-month follow-up, her hematochezia, abdominal pain and diarrhea were relieved. Furthermore, 16S rRNA sequencing of the feces showed that the intestinal bacterial composition of the patient obviously changed after FMT and became similar to that of the donors.<br><br>LESSONS: This case report shows that FMT can relieve the symptoms of hematochezia and diarrhea by changing the bacterial community structure in patients with chronic hemorrhagic radiation proctitis.}, }
@article {pmid32990503, year = {2020}, author = {Terveer, EM and Vendrik, KE and Ooijevaar, RE and Lingen, EV and Boeije-Koppenol, E and Nood, EV and Goorhuis, A and Bauer, MP and van Beurden, YH and Dijkgraaf, MG and Mulder, CJ and Vandenbroucke-Grauls, CM and Seegers, JF and van Prehn, J and Verspaget, HW and Kuijper, EJ and Keller, JJ}, title = {Faecal microbiota transplantation for Clostridioides difficile infection: Four years' experience of the Netherlands Donor Feces Bank.}, journal = {United European gastroenterology journal}, volume = {8}, number = {10}, pages = {1236-1247}, pmid = {32990503}, issn = {2050-6414}, mesh = {Abdominal Pain/epidemiology/etiology ; Adult ; Anti-Bacterial Agents/*therapeutic use ; *Biological Specimen Banks ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/microbiology/*therapy ; Diarrhea/epidemiology/etiology ; Donor Selection ; Feasibility Studies ; Fecal Microbiota Transplantation/*adverse effects ; Female ; Follow-Up Studies ; Humans ; Living Donors ; Male ; Middle Aged ; Nausea/epidemiology/etiology ; Netherlands/epidemiology ; Prospective Studies ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: The Netherlands Donor Feces Bank provides standardized ready-to-use donor faecal suspensions for faecal microbiota transplantation treatment of patients with recurrent Clostridioides difficile infection.<br><br>OBJECTIVE: The purpose of this study was evaluation of safety, feasibility and outcome of faecal microbiota transplantation facilitated by a national stool bank.<br><br>METHODS: The methods used included: observational cohort study of donors and recipients of faecal suspensions; assessment of donor screening and patient selection performed by an expert panel of medical microbiologists, gastroenterologists and infectious disease specialists; and patient outcome evaluated at different timepoints after faecal microbiota transplantation.<br><br>RESULTS: Of 871 volunteers who registered as a potential faeces donor, 16 (2%) became active donors. Nine donors stopped or were excluded after a mean donation period of 5.7 months. In 2016-2019, 47 (27%) of 176 requests for faecal microbiota transplantations were deemed not indicated by the expert panel. In total, 129 patients with recurrent C. difficile infection were treated with 143 faecal suspensions in 40 different hospitals. The cure rate at two months after a single infusion was 89% (107/120). Of 84 patients, long-term follow-up (median 42 weeks) was available and sustained cure was achieved in 61 (73%). Early C. difficile infection relapses (within two months after faecal microbiota transplantation) and late recurrences (after more than two months) occurred more frequently in patients who received non-C. difficile antibiotics within three weeks after faecal microbiota transplantation and in moderately to severely immunocompromised patients. Of 21 patients with C. difficile infection after faecal microbiota transplantation, 14 were cured with anti-C. difficile antibiotics and seven with a second transplantation. No faecal microbiota transplantation-related serious adverse events were observed, but gastro-intestinal complaints (nausea, abdominal pain or diarrhoea) persisted in 32% of the treated patients at long-term follow-up.<br><br>CONCLUSION: Faecal suspensions provided by a centralized stool bank, supported by a multidisciplinary expert team, resulted in effective, appropriate and safe application of faecal microbiota transplantation for recurrent C. difficile infection.<br><br>LEVEL OF EVIDENCE: Level II, prospective cohort study.}, }
@article {pmid32988391, year = {2020}, author = {Schwartz, DJ and Langdon, AE and Dantas, G}, title = {Understanding the impact of antibiotic perturbation on the human microbiome.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {82}, pmid = {32988391}, issn = {1756-994X}, support = {R01 AT009741/AT/NCCIH NIH HHS/United States ; TL1 TR002344/TR/NCATS NIH HHS/United States ; 1U1CI000033 301/CC/CDC HHS/United States ; R01 AI123394/AI/NIAID NIH HHS/United States ; TL1 TR000449/TR/NCATS NIH HHS/United States ; R01 HD092414/HD/NICHD NIH HHS/United States ; AT009741/AT/NCCIH NIH HHS/United States ; TL1 TR000449/NH/NIH HHS/United States ; }, mesh = {Age Factors ; Anti-Bacterial Agents/*pharmacology ; Drug Resistance, Microbial ; Gastrointestinal Microbiome/drug effects ; Humans ; Microbiota/*drug effects ; }, abstract = {The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome's ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.}, }
@article {pmid32987284, year = {2020}, author = {Proença, IM and Allegretti, JR and Bernardo, WM and de Moura, DTH and Ponte Neto, AM and Matsubayashi, CO and Flor, MM and Kotinda, APST and de Moura, EGH}, title = {Fecal microbiota transplantation improves metabolic syndrome parameters: systematic review with meta-analysis based on randomized clinical trials.}, journal = {Nutrition research (New York, N.Y.)}, volume = {83}, number = {}, pages = {1-14}, doi = {10.1016/j.nutres.2020.06.018}, pmid = {32987284}, issn = {1879-0739}, mesh = {Blood Glucose ; Cholesterol/blood ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Gastrointestinal Microbiome ; Glycated Hemoglobin/analysis ; Humans ; Insulin Resistance ; Male ; Metabolic Syndrome/microbiology/*therapy ; Obesity/microbiology/therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {Obesity and metabolic syndrome are important health problems that can lead to significant morbidity/mortality as well as subsequent health concerns. Alterations in the gut microbiota have been implicated in both obesity and metabolic syndrome. Fecal Microbiota Transplantation (FMT) has emerged as a new promising therapeutic approach aimed at manipulating the gut microbiota in various chronic diseases. Randomized clinical trials assessing the use of FMT in obese and metabolic syndrome patients have been reported. The purpose of this systematic review with meta-analysis using randomized clinical trials (RCT) is to evaluate the role of FMT for the treatment of obesity and metabolic syndrome and its impact on clinically relevant parameters. We searched the main databases, as well as the gray literature, to identify RCTs comparing FMT from lean donor(s) vs placebo for obese/metabolic syndrome patients. We included all studies that utilized any form of placebo (sham, saline, autologous FMT, or placebo capsules). Six studies met the inclusion criteria and were included for final analysis with a total of 154 patients. We looked for clinically significant parameters related to obesity and metabolic syndrome and organized the findings into early (2-6 weeks after intervention) and late (12 weeks after intervention) outcomes. Two to 6 weeks after intervention, mean HbA1c was lower in the FMT group (MD = -1.69 mmol/L, CI [-2.88, -0.56], P = .003) and mean HDL cholesterol was higher in the FMT group (MD = 0.09 mmol/L, CI [0.02, 0.15], P = .008). There was no difference in obesity parameters 6 to 12 weeks after intervention. No serious adverse events were reported. The findings for this meta-analysis show that FMT may have a role for the treatment of metabolic syndrome, but there is currently not enough evidence to support its use in clinical practice. High-quality well-powered RCTS with longer follow-up are necessary to clarify the role of FMT in this patient cohort.}, }
@article {pmid32987062, year = {2020}, author = {Goo, N and Bae, HJ and Park, K and Kim, J and Jeong, Y and Cai, M and Cho, K and Jung, SY and Kim, DH and Ryu, JH}, title = {The effect of fecal microbiota transplantation on autistic-like behaviors in Fmr1 KO mice.}, journal = {Life sciences}, volume = {262}, number = {}, pages = {118497}, doi = {10.1016/j.lfs.2020.118497}, pmid = {32987062}, issn = {1879-0631}, mesh = {Animals ; Autistic Disorder/microbiology/*therapy ; Behavior, Animal/physiology ; Brain/metabolism ; Cognitive Dysfunction/etiology/microbiology/therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Female ; Fragile X Mental Retardation Protein/*genetics ; Fragile X Syndrome/microbiology/psychology/*therapy ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; }, abstract = {The importance of alterations in bidirectional communication between gut and brain has become obvious in neuropsychiatric disorders. Gastrointestinal (GI) disturbances are very common in autism spectrum disorders (ASD), and the GI microbiota profiles in children with ASD are significantly different from those in the general population. Fragile X syndrome (FXS) is an inheritable developmental disability in humans, and patients with FXS exhibit autistic behaviors such as mental retardation and impaired social communication or interaction. We hypothesized that an increase in specific gut microbiota by fecal microbiota transplantation (FMT) would mitigate autistic-like behaviors. To test this hypothesis, we measured the effects of FMT from normal mice to Fmr1 KO mice on autistic-like behaviors using several behavioral tests. Because the amounts of A. muciniphila in Fmr1 KO mice was very low, we assessed A. muciniphila population, tested the expression of MUC2, and analyzed goblet cells in the gut after the FMT. We found that FMT ameliorated autistic-like behaviors, especially memory deficits and social withdrawal, and we observed that the levels of A. muciniphila were normalized to wild-type levels. In addition, FMT attenuated the increased levels of TNFα and Iba1 in the brains of Fmr1 KO mice. These results suggest that FMT could be a useful tool for the treatments of cognitive deficits and social withdrawal symptoms observed in FXS or ASD because it increases the population of A. muciniphila and decreases TNFα and Iba1 levels.}, }
@article {pmid32982371, year = {2020}, author = {Azimirad, M and Yadegar, A and Gholami, F and Shahrokh, S and Asadzadeh Aghdaei, H and Ianiro, G and Suzuki, H and Cammarota, G and Zali, MR}, title = {Treatment of Recurrent Clostridioides difficile Infection Using Fecal Microbiota Transplantation in Iranian Patients with Underlying Inflammatory Bowel Disease.}, journal = {Journal of inflammation research}, volume = {13}, number = {}, pages = {563-570}, pmid = {32982371}, issn = {1178-7031}, abstract = {PURPOSE: Fecal microbiota transplantation (FMT) is an effective treatment option for patients with recurrent Clostridioides difficile infection (rCDI). However, there is a paucity of evidence regarding its efficacy and safety in patients with rCDI and concurrent inflammatory bowel disease (IBD). Here, we present a single-center experience of FMT for treatment of rCDI in Iranian patients with IBD.<br><br>PATIENTS AND METHODS: Eight patients with established IBD (7 with ulcerative colitis and 1 with Crohn's disease) who underwent at least one FMT via colonoscopy for treatment of rCDI were enrolled in this study. Demographics, pre-FMT and post-FMT IBD activity, efficacy for rCDI and adverse events (AEs) were assessed during a 6-month follow-up period. All patients had experienced 3 episodes of rCDI and were refractory to conventional therapies with metronidazole and vancomycin. Primary cure and secondary cure rates were assessed after FMT treatments.<br><br>RESULTS: A total of 10 FMTs were performed via colonoscopy in 8 patients (6/8; 75% men) with a median age of 35 years (range: 22-60). Two patients received a second FMT. Overall, the primary and secondary cure rates were 75% and 100%, respectively. Two patients developed CPE-producing C. perfringens diagnoses after second FMTs. There were no other AEs, and no patient experienced IBD flare.<br><br>CONCLUSION: We demonstrated that FMT appears to be an effective, safe and rational therapeutic alternative for resolution of rCDI in patients with underlying IBD. Furthermore, we suggest implementing the CPE-producing C. perfringens testing in the screening of FMT donors.}, }
@article {pmid32981857, year = {2021}, author = {Albu, S and Kumru, H and Coll, R and Vives, J and Vallés, M and Benito-Penalva, J and Rodríguez, L and Codinach, M and Hernández, J and Navarro, X and Vidal, J}, title = {Clinical effects of intrathecal administration of expanded Wharton jelly mesenchymal stromal cells in patients with chronic complete spinal cord injury: a randomized controlled study.}, journal = {Cytotherapy}, volume = {23}, number = {2}, pages = {146-156}, doi = {10.1016/j.jcyt.2020.08.008}, pmid = {32981857}, issn = {1477-2566}, mesh = {Adult ; Female ; Humans ; Male ; *Mesenchymal Stem Cell Transplantation ; *Mesenchymal Stem Cells ; Middle Aged ; Quality of Life ; *Spinal Cord Injuries/therapy ; *Wharton Jelly ; }, abstract = {BACKGROUND AIMS: Spinal cord injury (SCI) represents a devastating condition leading to severe disability related to motor, sensory and autonomic dysfunction. Stem cell transplantation is considered a potential emerging therapy to stimulate neuroplastic and neuroregenerative processes after SCI. In this clinical trial, the authors investigated the safety and clinical recovery effects of intrathecal infusion of expanded Wharton jelly mesenchymal stromal cells (WJ-MSCs) in chronic complete SCI patients.<br><br>METHODS: The authors designed a randomized, double-blind, crossover, placebo-controlled, phase 1/2a clinical trial (NCT03003364). Participants were 10 patients (7 males, 3 females, age range, 25-47 years) with chronic complete SCI (American Spinal Injury Association A) at dorsal level (T3-11). Patients were randomly assigned to receive a single dose of intrathecal ex vivo-expanded WJ-MSCs (10&#xa0;&#xd7;&#xa0;10[6] cells) from human umbilical cord or placebo and were then switched to the other arm at 6 months. Clinical evaluation (American Spinal Injury Association impairment scale motor and sensory score, spasticity, neuropathic pain, electrical perception and pain thresholds), lower limb motor evoked potentials (MEPs) and sensory evoked potentials (SEPs), Spinal Cord Independence Measure and World Health Organization Quality of Life Brief Version were assessed at baseline, 1 month, 3 months and 6 months after each intervention. Urodynamic studies and urinary-specific quality of life (Qualiveen questionnaire) as well as anorectal manometry, functional assessment of bowel dysfunction (Rome III diagnostic questionnaire) and severity of fecal incontinence (Wexner score) were conducted at baseline and at 6 months after each intervention.<br><br>RESULTS: Intrathecal transplantation of WJ-MSCs was considered safe, with no significant side effects. Following MSC infusion, the authors found significant improvement in pinprick sensation in the dermatomes below the level of injury compared with placebo. Other clinically relevant effects, such as an increase in bladder maximum capacity and compliance and a decrease in bladder neurogenic hyperactivity and external sphincter dyssynergy, were observed only at the individual level. No changes in motor function, spasticity, MEPs, SEPs, bowel function, quality of life or independence measures were observed.<br><br>CONCLUSIONS: Intrathecal transplantation of human umbilical cord-derived WJ-MSCs is a safe intervention. A single intrathecal infusion of WJ-MSCs in patients with chronic complete SCI induced sensory improvement in the segments adjacent to the injury site.}, }
@article {pmid32981762, year = {2021}, author = {Martínez Pizarro, S}, title = {Transplantation of fecal microbiota in multidrug-resistant Klebsiella pneumoniae colonization and infection.}, journal = {Gastroenterologia y hepatologia}, volume = {44}, number = {3}, pages = {221-222}, doi = {10.1016/j.gastrohep.2020.06.009}, pmid = {32981762}, issn = {0210-5705}, mesh = {*Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; Humans ; Klebsiella Infections/*therapy ; *Klebsiella pneumoniae ; }, }
@article {pmid32981509, year = {2020}, author = {Gulati, M and Singh, SK and Corrie, L and Chandwani, L and Singh, A and Kapoor, B and Kumar, R and Pandey, NK and Kumar, B and Awasthi, A and Khursheed, R}, title = {Fecal Microbiota Transplant: Latest Addition to Arsenal Against Recurrent Clostridium Difficile Infection.}, journal = {Recent patents on anti-infective drug discovery}, volume = {}, number = {}, pages = {}, doi = {10.2174/1574891X15666200925092354}, pmid = {32981509}, issn = {2212-4071}, abstract = {An infectious disease of colon, recurrent Clostridium difficile infection (RCDI) is hitherto considered insurmountable leading to significant morbidity and mortality. Gut dysbiosis, generally resulting from frequent use of antibiotics is considered to be responsible for the etiopathogenesis of rCDI. Ironically, the conventional treatment strategies for the disease also include the use of anti-infective drugs such as metronidazole, vancomycin and fidaxomycin. As a result of the efforts to overcome the limitations of these treatment options to control recurrence of disease, Fecal Microbiota Transplant (FMT) has emerged as an effective and safe alternative. It is pertinent to add here that FMT is defined as the process of engraftment of fecal suspension from the healthy person into the gastrointestinal tract of the diseased individual aiming at the restoration of gut microbiota. FMT has proved to be quite successful in the treatment of recurrent and resistant Clostridium difficile infections (RCDI). In last three decades a lot of information has been generated on the use of FMT for RCDI. A number of clinical trials have been reported with generally very high success rates. However, very small number of patents could be found in the area indicating that there still exists lacuna in the knowledge about FMT with respect to its preparation, regulation, mode of delivery and safety. The current review attempts to dive deeper to discuss the patents available in the area while supporting the information contained therein with the non-patent literature.}, }
@article {pmid32980389, year = {2020}, author = {Shaffer, SR and Witt, J and Targownik, LE and Kao, D and Lee, C and Smieliauskas, F and Rubin, DT and Singh, H and Bernstein, CN}, title = {Cost-effectiveness analysis of a fecal microbiota transplant center for treating recurrent C.difficile infection.}, journal = {The Journal of infection}, volume = {81}, number = {5}, pages = {758-765}, doi = {10.1016/j.jinf.2020.09.025}, pmid = {32980389}, issn = {1532-2742}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/drug therapy ; Cost-Benefit Analysis ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; Vancomycin ; }, abstract = {OBJECTIVE: We assessed the cost-effectiveness of establishing a fecal microbial transplant (FMT) unit in Canada for the treatment of recurrent CDI.<br><br>DESIGN: We performed a cost-effectiveness analysis to determine the number of patients with recurrent CDI needed to treat (NNT) annually to make establishing a FMT unit cost-effective. We compared treating patients for their second recurrence of CDI with FMT in a jurisdiction with a FMT unit, compared to being treated with antibiotics; then sent to a medical center with FMT available for the third recurrence. We used a willingness to pay threshold of $50,000 per quality-adjusted-life-year gained.<br><br>RESULTS: The minimum annual NNT was 15 for FMT via colonoscopy, 17 for FMT via capsule, and 44 for FMT via enema compared with vancomycin, and 16, 18, and 47 compared with fidaxomicin, respectively. A medical center's minimum catchment area when establishing a FMT unit would have to be 56,849 if using FMT via colonoscopy, or 64,429 if using capsules.<br><br>CONCLUSION: We report the minimum number of patients requiring treatment annually with FMT to achieve cost-effectiveness, when including start-up and ongoing costs. FMT is cost-effective in Canada in populations with a sufficient number of eligible patients, ranging from 15 to 47 depending on the FMT modality used. This is crucial for medical jurisdictions making decisions about establishing a FMT unit for the treatment of recurrent CDI. The cost-effectiveness can be generalized in other countries.}, }
@article {pmid32979504, year = {2020}, author = {Coman, V and Vodnar, DC}, title = {Gut microbiota and old age: Modulating factors and interventions for healthy longevity.}, journal = {Experimental gerontology}, volume = {141}, number = {}, pages = {111095}, pmid = {32979504}, issn = {1873-6815}, mesh = {Aged ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Longevity ; Prebiotics ; *Synbiotics ; }, abstract = {Our gut microbiota is a complex and dynamic ecosystem with a paramount role in shaping our metabolic and immunological functions. Recent research suggests that aging may negatively affect the composition, diversity, and function of our microbiota mainly due to alterations in diet and immunologic reactivity (i.e. immunosenescence), and increased incidence of certain diseases and, therefore, increased exposure to certain medication (e.g. antibiotics, proton pump inhibitors). In turn, this aging-related gut dysbiosis may contribute to the initiation and/or progress of other metabolic diseases, and consequently, to a decrease in healthy longevity. On the positive side, promising therapeutic interventions, such as diet supplementation with prebiotics, probiotics and synbiotics, or fecal microbiota transplantation, aimed to counteract these aging-related deleterious consequences, could improve our health, and extend our healthy lifespan. In this context, the current review aims to assess the latest progress in identifying the key elements affecting the gut microbiota of the older adults and their mechanism of action, and the effectiveness of the therapeutic interventions aimed at restoring the diversity and healthy functions of the gut microbiota in older individuals.}, }
@article {pmid32979161, year = {2020}, author = {Roshan, N and Clancy, AK and Borody, TJ}, title = {Faecal Microbiota Transplantation is Effective for the Initial Treatment of Clostridium difficile Infection: A Retrospective Clinical Review.}, journal = {Infectious diseases and therapy}, volume = {9}, number = {4}, pages = {935-942}, pmid = {32979161}, issn = {2193-8229}, abstract = {INTRODUCTION: Clostridium difficile (C. difficile) infection (CDI) is commonly recognised as a nosocomial infection but is increasingly identified in patients in the community. Antimicrobial exposure which compromises gut microbiota is the main risk factor for CDI, although antibiotics remain the main treatment for this infection. Faecal microbiota transplantation (FMT) is also an effective treatment for CDI. FMT involves the transfer of microbiota from a healthy donor to an unwell patient. Currently FMT is mostly used after repeated antibiotic treatments fail to cure CDI. This study investigated the effect of FMT as first-line treatment for CDI to avoid repeated antibiotic damage of the microbiome.<br><br>METHODS: This retrospective, single-centre study included 59 patients between 2012 and 2017 whose first episode of CDI was treated with FMT. The patients' symptoms and presence of C.&#xa0;difficile in stool samples both at the baseline and post treatment were documented.<br><br>RESULTS: Fifty-four patients completed a final stool test 4-8&#xa0;weeks post treatment in which 98% of patients were negative for C.&#xa0;difficile. There were no adverse effects. There was a significant reduction in abdominal pain, diarrhoea, bloating and blood in the stool at 4-8&#xa0;weeks post treatment. Data from 24 patients who completed an extended 6&#xa0;months follow-up showed significant reduction in abdominal pain, diarrhoea and blood in the stool.<br><br>CONCLUSION: This study demonstrates the safety and efficacy of FMT as first-line treatment for patients' initial episode of CDI. Future randomised studies are required to confirm FMT as the initial treatment for CDI.}, }
@article {pmid32976567, year = {2021}, author = {Saha, S and Mara, K and Pardi, DS and Khanna, S}, title = {Durability of Response to Fecal Microbiota Transplantation After Exposure to Risk Factors for Recurrence in Patients With Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {73}, number = {7}, pages = {e1706-e1712}, pmid = {32976567}, issn = {1537-6591}, support = {U01 FD005938/FD/FDA HHS/United States ; UL1 TR000135/TR/NCATS NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Adult ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; *Neoplasms ; Recurrence ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI.<br><br>METHODS: We conducted a retrospective study of adults undergoing FMT for recurrent CDI. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, non-CDI antibiotic use, acid suppressant medications), and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure.<br><br>RESULTS: Overall, 460 patients were included (median age, 57 years [18-94]; 65.2% female). Comorbidities included chronic liver disease, 12.8% (n&#x2005;=&#x2005;59); cancer, 11.7% (n&#x2005;=&#x2005;54); chronic kidney disease, 3.9% (n&#x2005;=&#x2005;18); and inflammatory bowel disease, 21.9% (n&#x2005;=&#x2005;101). Overall, 31.3% (n&#x2005;=&#x2005;144) received antibiotics, 21.7% (n&#x2005;=&#x2005;100) received acid suppressants, and 76.8% (n&#x2005;=&#x2005;350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% (95% confidence interval [CI], 72.7%-84.0%) had durable response to FMT at 1 year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT (hazard ratio, 0.27; 95% CI, .15-.49; P&#x2005;<&#x2005;.001).<br><br>CONCLUSIONS: The majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics.}, }
@article {pmid32973502, year = {2020}, author = {Cai, TT and Ye, XL and Li, RR and Chen, H and Wang, YY and Yong, HJ and Pan, ML and Lu, W and Tang, Y and Miao, H and Snijders, AM and Mao, JH and Liu, XY and Lu, YB and Ding, DF}, title = {Resveratrol Modulates the Gut Microbiota and Inflammation to Protect Against Diabetic Nephropathy in Mice.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {1249}, pmid = {32973502}, issn = {1663-9812}, abstract = {Oral administration of resveratrol is able to ameliorate the progression of diabetic nephropathy (DN); however, its mechanisms of action remain unclear. Recent evidence suggested that the gut microbiota is involved in the metabolism therapeutics. In the current study, we sought to determine whether the anti-DN effects of resveratrol are mediated through modulation of the gut microbiota using the genetic db/db mouse model of DN. We demonstrate that resveratrol treatment of db/db mice relieves a series of clinical indicators of DN. We then show that resveratrol improves intestinal barrier function and ameliorates intestinal permeability and inflammation. The composition of the gut microbiome was significantly altered in db/db mice compared to control db/m mice. Dysbiosis in db/db mice characterized by low abundance levels of Bacteroides, Alistipes, Rikenella, Odoribacter, Parabacteroides, and Alloprevotella genera were reversed by resveratrol treatment, suggesting a potential role for the microbiome in DN progression. Furthermore, fecal microbiota transplantation, derived from healthy resveratrol-treated db/m mice, was sufficient to antagonize the renal dysfunction, rebalance the gut microbiome and improve intestinal permeability and inflammation in recipient db/db mice. These results indicate that resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol, which provides supporting evidence for the gut-kidney axis in DN.}, }
@article {pmid32971101, year = {2020}, author = {Wang, L and An, J and Song, S and Mei, M and Li, W and Ding, F and Liu, S}, title = {Electroacupuncture preserves intestinal barrier integrity through modulating the gut microbiota in DSS-induced chronic colitis.}, journal = {Life sciences}, volume = {261}, number = {}, pages = {118473}, doi = {10.1016/j.lfs.2020.118473}, pmid = {32971101}, issn = {1879-0631}, mesh = {Animals ; Colitis/chemically induced/metabolism/pathology/*therapy ; Dextran Sulfate ; *Electroacupuncture ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Intestinal Mucosa/metabolism/pathology ; Intestines/*pathology ; Male ; Mice, Inbred C57BL ; Permeability ; }, abstract = {AIMS: Electroacupuncture (EA) at ST36 has been verified to ameliorate experimental acute colitis. However, the effect of EA on chronic colitis and its mechanism has not yet been explored. This study aimed to assess the protective effect of EA against chronic colitis and the related mechanisms.<br><br>MAIN METHODS: Chronic colitis was induced by dextran sulfate sodium (DSS) in C57BL/6 mice, and EA was applied throughout the entire experiment. Colonic inflammation and intestinal barrier integrity were evaluated. Alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing. The fecal microbiota transplantation (FMT) experiment was used to further confirm the effect of the gut microbiota on the barrier protective effect of EA. The potential molecular mechanisms were explored by western blotting.<br><br>KEY FINDINGS: (1) EA lowered the disease activity index (DAI) and histological scores, decreased the levels of TNF&#x3b1;, IL1&#x3b2;, IL6 and iNOS, and increased the IL10 level in DSS-induced chronic colitis. (2) EA upregulated the protein expression of ZO-1, Occludin, E-Cadherin and mucin2 (MUC2), reduced the apoptosis and proliferation of intestinal epithelial cells (IECs) and intestinal permeability. (3) EA enhanced the gut microbiota diversity and restored the community structure. (4) Both the low-frequency EA (LEA) FMT and high-frequency EA (HEA) FMT maintained the intestinal barrier integrity. (5) EA promoted activation of the mitogen activated protein kinase (MAPK) signaling pathway.<br><br>SIGNIFICANCE: EA can relieve chronic experimental colitis, and this effect may depend on activation of the MAPK signaling pathway through modulation of the gut microbiota to preserve the intestinal barrier.}, }
@article {pmid32970852, year = {2020}, author = {Ross, CN and Reveles, KR}, title = {Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets.}, journal = {American journal of primatology}, volume = {82}, number = {12}, pages = {e23196}, pmid = {32970852}, issn = {1098-2345}, support = {P30 AG044271/AG/NIA NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Animals, Zoo/microbiology ; Bacteria/*classification ; Bacterial Physiological Phenomena ; Callithrix/*microbiology ; Feasibility Studies ; Fecal Microbiota Transplantation/*veterinary ; *Gastrointestinal Microbiome ; Male ; Texas ; }, abstract = {Disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving healthspan and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. This was a prospective study of marmosets housed at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. Eligible animals included healthy young adult males (age 2-5 years) with no recent medication use. Stool from two donors was combined and administered in 0.5 ml doses to five young recipients once weekly for 3 weeks. Safety outcomes and alterations in the gut microbiome composition via 16S ribosomal RNA sequencing were compared at baseline and monthly up to 6 months post-FMT. Overall, significant differences in the percent relative abundance was seen in FMT recipients at the phylum and family levels from baseline to 1 month and baseline to 6 months post-FMT. In permutational multivariate analysis of variance analyses, treatment status (donor vs. recipient) (p = .056) and time course (p = .019) predicted β diversity (p = .056). The FMT recipients did not experience any negative health outcomes over the course of the treatment. FMT via oral gavage was safe to administer to young adult marmosets. The marmoset microbiome may be altered by FMT; however, progressive changes in the microbiome are strongly driven by the host and its baseline microbiome composition.}, }
@article {pmid32970314, year = {2021}, author = {Chindaratana, K and Tanpowpong, P and Lertudomphonwanit, C and Treepongkaruna, S}, title = {Gastrointestinal protein loss in children with portal hypertension.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {40}, number = {3}, pages = {333-337}, pmid = {32970314}, issn = {0975-0711}, mesh = {Adult ; *Biliary Atresia ; Child ; Female ; Humans ; *Hypertension, Portal/etiology ; Infant ; *Liver Transplantation ; }, abstract = {Portal hypertension increases pressure in lymphatic ducts, which may lead to gastrointestinal (GI) protein loss. Reports have shown that adults with portal hypertension had resolution of protein-losing enteropathy after transplantation; but studies in children are very limited. We therefore aimed to evaluate GI protein loss in children with portal hypertension and defined changes after liver transplantation. Children aged 3 months to 18 years with portal hypertension and the age-matched healthy controls were enrolled during August 2018 to September 2019. Random fecal alpha-1 antitrypsin measurements were obtained at the initial visit, 3 months later, 1 week before, and 3 months after liver transplantation (if applicable). One or more positive test (> 0.795 mg/dL) was interpreted as a positive result. We enrolled 76 children (n = 38 in each group) with a median age of 15.5 months (interquartile range [IQR], 11.2-41.7), female 51%, and 92% with biliary atresia in the portal hypertension group. We noted GI protein loss in 4/38 children (10.5%) with portal hypertension, while none in the controls (p = 0.11). We found no significant differences on the markers of severity of liver disease and serum albumin between patients with vs. the ones without GI protein loss (p > 0.05). After liver transplantation, 2/4 patients with GI protein loss had undetectable loss. We found that, in a small group of children, 10.5% with portal hypertension had notable GI protein loss without significant relationships with the severity of liver disease.}, }
@article {pmid32969566, year = {2021}, author = {Bonfili, L and Cecarini, V and Gogoi, O and Gong, C and Cuccioloni, M and Angeletti, M and Rossi, G and Eleuteri, AM}, title = {Microbiota modulation as preventative and therapeutic approach in Alzheimer's disease.}, journal = {The FEBS journal}, volume = {288}, number = {9}, pages = {2836-2855}, doi = {10.1111/febs.15571}, pmid = {32969566}, issn = {1742-4658}, mesh = {Alzheimer Disease/*microbiology/pathology/prevention &amp; control/therapy ; Antioxidants/therapeutic use ; Brain/metabolism/pathology ; Gastrointestinal Microbiome/*genetics ; Humans ; Inflammation/*drug therapy/genetics ; Neuroprotective Agents/therapeutic use ; }, abstract = {The gut microbiota coevolves with its host, and numerous factors like diet, lifestyle, drug intake and geographical location continuously modify its composition, deeply influencing host health. Recent studies demonstrated that gut dysbiosis can alter normal brain function through the so-called gut-brain axis, a bidirectional communication network between the central nervous system and the gastrointestinal tract, thus playing a key role in the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD). In this perspective, in the constant search for novel treatments in AD, the rational modulation of gut microbiota composition could represent a promising approach to prevent or delay AD onset or to counteract its progression. Preclinical and human studies on microbiota modulation through oral bacteriotherapy and faecal transplantation showed anti-inflammatory and antioxidant effects, upregulation of plasma concentration of neuroprotective hormones, restoration of impaired proteolytic pathways, amelioration of energy homeostasis with consequent decrease of AD molecular hallmarks and improvement of behavioural and cognitive performances. In this review, we dissect the role of gut microbiota in AD and highlight recent advances in the development of new multitarget strategies for microbiota modulation to be used as possible preventative and therapeutic approaches in AD.}, }
@article {pmid32967718, year = {2020}, author = {Yan, L and Sun, J and Xu, X and Huang, S}, title = {Epidemiology and risk factors of rectal colonization of carbapenemase-producing Enterobacteriaceae among high-risk patients from ICU and HSCT wards in a university hospital.}, journal = {Antimicrobial resistance and infection control}, volume = {9}, number = {1}, pages = {155}, pmid = {32967718}, issn = {2047-2994}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacterial Proteins/*genetics ; Carbapenem-Resistant Enterobacteriaceae/*classification/genetics/isolation &amp; purification ; Case-Control Studies ; Cross Infection/*epidemiology ; Enterobacteriaceae Infections/*epidemiology ; Female ; Genotype ; Hematopoietic Stem Cell Transplantation ; Hospitals, University ; Humans ; Inpatients ; Intensive Care Units ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Multilocus Sequence Typing ; Phylogeny ; Prevalence ; Prospective Studies ; Rectum/*microbiology ; Risk Factors ; beta-Lactamases/*genetics ; }, abstract = {BACKGROUND: Nosocomial carbapenemase-producing Enterobacterieceae (CPE) infections constitute a major global health concern and are associated with increased morbidity and mortality. Rectal colonization with CPE is a risk factor for bacterial translocation leading to subsequent endogenous CPE infections. This prospective observational study was aimed to investigate the prevalence and epidemiology of rectal colonization of CPE, the carbapenemase genotypes, and to identify the independent risk factors for the acquisition of CPE colonization in high-risk patients from ICU and HSCT wards in a university hospital in China.<br><br>METHODS: In a prospective cohort study, 150 fecal samples from rectal swabs were consecutively obtained for inpatients from the intensive care unit (ICU) and hematopoietic stem cell transplantation (HSCT) wards from November 2018 to May 2019, and screening test for CPE was conducted by using prepared in-house trypsin soybean broth (TSB) selective media and MacConkey agar. Antimicrobial susceptibility was determined by the broth microdilution method and carbapenemase genes were characterized by both the GeneXpert Carba-R and PCR for blaKPC, blaNDM, blaIMP, blaVIM and blaOXA. Multi-locus sequence typing (MLST) was employed to characterize the genetic relationships among the carbapenemase-producing K. Pneumonia (CPKP) isolates. In order to further investigate the risk factors and clinical outcomes of CPE colonization, a prospective case-control study was also performed.<br><br>RESULTS: Twenty-six suspected CPE strains, including 17&#x2009;Klebsiella pneumoniae, 6 Escherichia coli, 1 Citrobacter freundii, 1 Enterobacter Kobe, and 1 Raoultella ornithinolytica, were identified in 25 non-duplicated rectal swab samples from 25 patients, with a carriage rate of 16.67% (25/150). Through GeneXpert Carba-R and subsequent PCR and sequencing, all the suspected CPE isolates were identified to be positive for the carbapenemase genes, of which 17 were blaKPC-carriers, and another 9 were blaNDM-producers. MLST designated all the CPKP isolates to be ST11 clone. Multivariate analysis indicated that urinary system diseases, operation of bronchoscopy, and combined use of antibiotics were independent risk factors for acquiring CPE colonization in high-risk patients from the ICU and HSCT wards.<br><br>CONCLUSIONS: This study revealed a high prevalence of rectal CPE colonization in high-risk patients from ICU and HSCT wards, and a predominant colonization of the KPC-producing K. pneumoniae clone ST11. Stricter infection control measures are urgently needed to limit the dissemination of CPE strains, especially in patients who were afflicted by urinary system diseases, have underwent bronchoscopy, and were previously exposed to combined antibiotic use.}, }
@article {pmid32966574, year = {2021}, author = {Khanna, S and Pardi, DS and Jones, C and Shannon, WD and Gonzalez, C and Blount, K}, title = {RBX7455, a Non-frozen, Orally Administered Investigational Live Biotherapeutic, Is Safe, Effective, and Shifts Patients' Microbiomes in a Phase 1 Study for Recurrent Clostridioides difficile Infections.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {73}, number = {7}, pages = {e1613-e1620}, pmid = {32966574}, issn = {1537-6591}, support = {WO2019213595//Rebiotix/ ; }, mesh = {Adult ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/drug therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Recurrent Clostridioides difficile infections (rCDI) are a global public health threat. To reduce rCDI, microbiota-restoring therapies are needed, particularly standardized, easy-to-administer formulations.<br><br>METHODS: This phase I open-label trial assessed the safety, efficacy in preventing rCDI recurrence, and intestinal microbiome effects of RBX7455, a room temperature-stable, orally administered investigational live biotherapeutic. Adult participants with 1 or more prior episodes of rCDI received: 4 RBX7455 capsules twice daily for 4 days (group 1); 4 RBX7455 capsules twice daily for 2 days (group 2); or 2 RBX7455 capsules twice daily for 2 days (group 3). For all groups, the first dose was administered in clinic, with remaining doses self-administered at home. Adverse events were monitored during and for 6 months after treatment. Treatment success was defined as rCDI prevention through 8 weeks after treatment. Participants' microbiome composition was assessed prior to and for 6 months after treatment.<br><br>RESULTS: Nine of 10 group 1 patients (90%), 8 of 10 group 2 patients (80%), and 10 of 10 group 3 patients (100%) were recurrence-free at the 8-week endpoint with durability to 6 months. Seventy-five treatment-emergent adverse events were observed in 27 participants with no serious investigational product-related events. Prior to treatment, participants' microbiomes were dissimilar from the RBX7455 composition with decreased Bacteroidia- and Clostridia-class bacteria, whereas after treatment, responders' microbiomes showed increased Bacteroidia and Clostridia.<br><br>CONCLUSIONS: Three dosing regimens of RBX7455 were safe and effective at preventing rCDI. Responders' microbiomes converged toward the composition of RBX7455. These results support its continued clinical evaluation.<br><br>CLINICAL TRIALS REGISTRATION: NCT02981316.}, }
@article {pmid32962069, year = {2020}, author = {Cold, F and Kousgaard, SJ and Halkjaer, SI and Petersen, AM and Nielsen, HL and Thorlacius-Ussing, O and Hansen, LH}, title = {Fecal Microbiota Transplantation in the Treatment of Chronic Pouchitis: A Systematic Review.}, journal = {Microorganisms}, volume = {8}, number = {9}, pages = {}, pmid = {32962069}, issn = {2076-2607}, support = {7076-00129B//Danish Innovation Fund/ ; }, abstract = {The objective was to evaluate available literature on treatment of chronic pouchitis with fecal microbiota transplantation (FMT) focusing on clinical outcomes, safety, and different approaches to FMT preparation and delivery. A systematic review of electronic databases was conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials Library from inception through April 2020. Human studies of all study types reporting results of FMT to treat chronic pouchitis were included. Nine studies, reporting FMT treatment of 69 patients with chronic pouchitis were found eligible for the review. Most studies were case series and cohort studies rated as having fair to poor quality due to high risk of bias and small sample size. Only one randomized controlled trial was included, finding no beneficial effect of FMT. In total clinical response after FMT was reported in 14 (31.8%) out of 44 evaluated patients at various timepoints after FMT, and clinical remission in ten (22.7%) patients. Only minor self-limiting adverse events were reported. FMT varied greatly regarding preparation, length of treatment, and route of delivery. The effects of FMT on symptoms of chronic pouchitis are not established, though some studies show promising results. Future controlled well-designed studies are warranted.}, }
@article {pmid32961549, year = {2021}, author = {Youngster, I}, title = {Another Step in the Journey-From Feces to Regulated Microbial Therapeutics.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {73}, number = {7}, pages = {e1621-e1623}, doi = {10.1093/cid/ciaa1435}, pmid = {32961549}, issn = {1537-6591}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid32957333, year = {2020}, author = {Mao, D and Jiang, Q and Sun, Y and Mao, Y and Guo, L and Zhang, Y and Man, M and Ouyang, G and Sheng, L}, title = {Treatment of intestinal graft-versus-host disease with unrelated donor fecal microbiota transplantation capsules: A case report.}, journal = {Medicine}, volume = {99}, number = {38}, pages = {e22129}, pmid = {32957333}, issn = {1536-5964}, mesh = {Adult ; Capsules ; *Fecal Microbiota Transplantation ; Graft vs Host Disease/*therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Intestinal Diseases/*therapy ; Male ; Myelodysplastic Syndromes/therapy ; Unrelated Donors ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD. Patient concerns: A 31-year-old male who was diagnosed as "myelodysplastic syndromes with excess blasts II" (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation.<br><br>DIAGNOSIS: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy.<br><br>INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2&#x200a;mg/kg/d) combined with recombinant human tumor necrosis factor-&#x3b1; receptorII: IgG Fc fusion protein (25&#x200a;mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out.<br><br>OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before.<br><br>CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD.<br><br>RATIONALE: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD.<br><br>PATIENT CONCERNS: A 31-year-old male who was diagnosed as "myelodysplastic syndromes with excess blasts II" (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation.<br><br>DIAGNOSES: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy.<br><br>INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2&#x200a;mg/kg/d) combined with recombinant human tumor necrosis factor-a receptorII: IgG Fc fusion protein (25&#x200a;mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out.<br><br>OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before.<br><br>CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD.<br><br>LESSONS: There is still a possibility of recurrence after the treatment of GvHD with capsule fecal microbiota transplantation. How to optimize the dosage and treatment course of fecal microbiota capsule administration needs further exploration.}, }
@article {pmid32955790, year = {2021}, author = {Magro, B and Mazzola, A and Munteanu, M and Goumard, C and Martinez, V and Bernard, D and Scatton, O and Battaglia, S and Celsa, C and Cammà, C and Conti, F}, title = {Consequences of Extended Spectrum Beta-Lactamase-Producing Enterobacteriaceae and Methicillin-Resistant Staphylococcus aureus Carriage in Awaiting Liver Transplant Patients.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {27}, number = {1}, pages = {43-54}, doi = {10.1002/lt.25897}, pmid = {32955790}, issn = {1527-6473}, mesh = {Aged ; *End Stage Liver Disease/surgery ; Enterobacteriaceae ; *Enterobacteriaceae Infections/diagnosis/epidemiology ; Female ; Humans ; *Liver Transplantation ; Male ; *Methicillin-Resistant Staphylococcus aureus ; Middle Aged ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; beta-Lactamases ; }, abstract = {Infections in patients with cirrhosis are associated with liver-related complications (LRCs), especially in patients awaiting liver transplantation (LT). The aim of this study was to evaluate the impact of methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase colonization on infections and LRCs for patients on the wait list and on infections after LT. We retrospectively included 250 of 483 patients with cirrhosis who were placed on the wait list for LT from December 2015 to January 2018. These patients were screened for MRSA or extended spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) at the time of wait-list placement and after LT. Of the patients, 76% were male with a mean age of 57.5 ± 10 years, and the most frequent cause of liver disease was alcohol (39%). Median Model for End-Stage Liver Disease (MELD) score was 19 (12-28). Only 1 patient was positive for MRSA; 19% of patients (n = 47) had ESBLE fecal carriage at the time of wait-list placement and 15% (n = 37) had it after LT. Infection-free survival on the wait list and after LT, according to fecal carriage status, was not statistically different between 2 groups. LRC-free survival at 6 and 12 months was significantly lower in ESBLE fecal carriage (HR, 1.6; P = 0.04). MELD score >19 (HR, 3.0; P = 0.01) and occurrence of infection during the first 3 months on the wait list (HR, 4.13; P < 0.001) were independent risk factors for LRC occurrence in the multivariate analysis. Our study is the first showing that in a cohort of patients with cirrhosis waiting for LT LRC-free survival was lower in patients with ESBLE fecal carriage but that infection-free survival was not different between the 2 groups.}, }
@article {pmid32955197, year = {2020}, author = {Li, Q and Ding, X and Liu, K and Marcella, C and Liu, X and Zhang, T and Liu, Y and Li, P and Xiang, L and Cui, B and Wang, J and Bai, J and Zhang, F}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes.}, journal = {Clinical and translational gastroenterology}, volume = {11}, number = {8}, pages = {e00224}, pmid = {32955197}, issn = {2155-384X}, mesh = {Adolescent ; Adult ; Child ; Colitis, Ulcerative/immunology/microbiology/*therapy ; DNA, Bacterial/isolation &amp; purification ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Remission Induction/methods ; Retreatment/adverse effects/methods ; *Time-to-Treatment ; Treatment Outcome ; Young Adult ; }, abstract = {INTRODUCTION: The previous researches aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) in a short-term observation. The present study aimed to explore the optimum timing of FMT for maintaining the long-term clinical benefits and to target the gut microbiota that may help to predict the long-term success or failure of FMT in UC.<br><br>METHODS: Two hundred two patients with UC were recruited from November 2012 to September 2018. The primary endpoint of this study was the maintaining time of the first and second courses of FMT. Relapse was defined as partial Mayo score &#x2265;2 after achieving clinical remission and an increase of partial Mayo score &#x2265;1 after achieving clinical response. The stool samples were analyzed by 16S rRNA gene sequencing.<br><br>RESULTS: The median maintaining time of the efficacy was 120 days (IQR, 45-180) and 182.5 days (IQR, 105-311.25) from the first course and second course of FMT, respectively. No FMT-related serious adverse events were observed. The differences of the relative abundance in Eggerthella, Lactobacillus, and Ruminococcus between pre-FMT and 5 days post-FMT were remarkably correlated with the long-term clinical remission (P < 0.05).<br><br>DISCUSSION: This study demonstrated that patients with UC should undergo the second course of FMT within 4 months after the first course of FMT for maintaining the long-term clinical benefits. The short-term alterations of microbiota after FMT may be conducive to predicting the long-term efficacy of FMT in UC (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/CTG/A363).}, }
@article {pmid32955166, year = {2021}, author = {Constante, M and De Palma, G and Lu, J and Jury, J and Rondeau, L and Caminero, A and Collins, SM and Verdu, EF and Bercik, P}, title = {Saccharomyces boulardii CNCM I-745 modulates the microbiota-gut-brain axis in a humanized mouse model of Irritable Bowel Syndrome.}, journal = {Neurogastroenterology and motility}, volume = {33}, number = {3}, pages = {e13985}, doi = {10.1111/nmo.13985}, pmid = {32955166}, issn = {1365-2982}, support = {//CIHR/Canada ; }, mesh = {Animals ; Anxiety/*microbiology/physiopathology ; Brain/metabolism/*physiopathology ; Case-Control Studies ; Colon/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Transit/*physiology ; Germ-Free Life ; Humans ; Indoleacetic Acids/metabolism ; Intestinal Mucosa/*metabolism ; Irritable Bowel Syndrome/metabolism/*microbiology/physiopathology ; Male ; Mice ; Permeability ; *Saccharomyces boulardii ; TRPV Cation Channels/metabolism ; }, abstract = {BACKGROUND: Gnotobiotic mice colonized with microbiota from patients with irritable bowel syndrome (IBS) and comorbid anxiety (IBS+A) display gut dysfunction and anxiety-like behavior compared to mice colonized with microbiota from healthy volunteers. Using this model, we tested the therapeutic potential of the probiotic yeast Saccharomyces boulardii strain CNCM I-745 (S. bou) and investigated underlying mechanisms.<br><br>METHODS: Germ-free Swiss Webster mice were colonized with fecal microbiota from an IBS+A patient or a healthy control (HC). Three weeks later, mice were gavaged daily with S.&#xa0;boulardii or placebo for two weeks. Anxiety-like behavior (light preference and step-down tests), gastrointestinal transit, and permeability were assessed. After sacrifice, samples were taken for gene expression by NanoString and qRT-PCR, microbiota 16S rRNA profiling, and indole quantification.<br><br>KEY RESULTS: Mice colonized with IBS+A microbiota developed faster gastrointestinal transit and anxiety-like behavior (longer step-down latency) compared to mice with HC microbiota. S.&#xa0;bou administration normalized gastrointestinal transit and anxiety-like behavior in mice with IBS+A microbiota. Step-down latency correlated with colonic Trpv1 expression and was associated with altered microbiota profile and increased Indole-3-acetic acid (IAA) levels.<br><br>CONCLUSIONS &amp; INFERENCES: Treatment with S. bou improves gastrointestinal motility and anxiety-like behavior in mice with IBS+A microbiota. Putative mechanisms include effects on pain pathways, direct modulation of the microbiota, and indole production by commensal bacteria.}, }
@article {pmid32954843, year = {2020}, author = {Ianiro, G and Segal, JP and Mullish, BH and Quraishi, MN and Porcari, S and Fabiani, G and Gasbarrini, A and Cammarota, G}, title = {Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders.}, journal = {Future microbiology}, volume = {15}, number = {}, pages = {1173-1183}, doi = {10.2217/fmb-2020-0061}, pmid = {32954843}, issn = {1746-0921}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Intestinal Diseases/microbiology/*therapy ; Metabolic Diseases/microbiology/*therapy ; Nervous System Diseases/microbiology/*therapy ; }, abstract = {Fecal microbiota transplantation (FMT) is the infusion of feces from a healthy donor into the gut of a recipient to treat a dysbiosis-related disease. FMT has been proven to be a safe and effective treatment for Clostridioides difficile infection, but increasing evidence supports the role of FMT in other gastrointestinal and extraintestinal diseases. The aim of this review is to paint the landscape of current evidence of FMT in different fields of application (including irritable bowel syndrome, inflammatory bowel disease, liver disorders, decolonization of multidrug-resistant bacteria, metabolic disorders and neurological disorders), as well as to discuss the current regulatory scenario of FMT, and hypothesize future directions of FMT.}, }
@article {pmid32953854, year = {2020}, author = {Zhong, M and Sun, Y and Wang, HG and Marcella, C and Cui, BT and Miao, YL and Zhang, FM}, title = {Awareness and attitude of fecal microbiota transplantation through transendoscopic enteral tubing among inflammatory bowel disease patients.}, journal = {World journal of clinical cases}, volume = {8}, number = {17}, pages = {3786-3796}, pmid = {32953854}, issn = {2307-8960}, abstract = {BACKGROUND: Transendoscopic enteral tubing (TET) has been used in China as a novel delivery route for fecal microbiota transplantation (FMT) into the whole colon with a high degree of patient satisfaction among adults.<br><br>AIM: To explore the recognition and attitudes of FMT through TET in patients with inflammatory bowel disease (IBD).<br><br>METHODS: An anonymous questionnaire, evaluating their awareness and attitudes toward FMT and TET was distributed among IBD patients in two provinces of Eastern and Southwestern China. Question formats included single-choice questions, multiple-choice questions and sorting questions. Patients who had not undergone FMT were mainly investigated for their cognition and acceptance of FMT and TET. Patients who had experience of FMT, the way they underwent FMT and acceptance of TET were the main interest. Then all the patients were asked whether they would recommend FMT and TET. This study also analyzed the preference of FMT delivery in IBD patients and the patient-related factors associated with it.<br><br>RESULTS: A total of 620 eligible questionnaires were included in the analysis. The survey showed that 44.6% (228/511) of patients did not know that FMT is a therapeutic option in IBD, and 80.6% (412/511) of them did not know the concept of TET. More than half (63.2%, 323/511) of the participants stated that they would agree to undergo FMT through TET. Of the patients who underwent FMT via TET [62.4% (68/109)], the majority [95.6% (65/68)] of them were satisfied with TET. Patients who had undergone FMT and TET were more likely to recommend FMT than patients who had not (94.5% vs 86.3%, P = 0.018 and 98.5% vs 87.8%, P = 0.017). Patients' choice for the delivery way of FMT would be affected by the type of disease and whether the patient had the experience of FMT. When compared to patients without experience of FMT, Crohn's disease and ulcerative colitis patients who had experience of FMT preferred mid-gut TET (P < 0.001) and colonic TET (P < 0.001), respectively.<br><br>CONCLUSION: Patients' experience of FMT through TET lead them to maintain a positive attitude towards FMT. The present findings highlighted the significance of patient education on FMT and TET.}, }
@article {pmid32952613, year = {2020}, author = {Segal, JP and Mullish, BH and Quraishi, MN and Iqbal, T and Marchesi, JR and Sokol, H}, title = {Mechanisms underpinning the efficacy of faecal microbiota transplantation in treating gastrointestinal disease.}, journal = {Therapeutic advances in gastroenterology}, volume = {13}, number = {}, pages = {1756284820946904}, pmid = {32952613}, issn = {1756-283X}, abstract = {Faecal microbiota transplantation (FMT) is currently a recommended therapy for recurrent/refractory Clostridioides difficile infection (CDI). The success of FMT for CDI has led to interest in its therapeutic potential in many other disorders. The mechanisms that underpin the efficacy of FMT are not fully understood. Importantly, FMT remains a crucial treatment in managing CDI and understanding the mechanisms that underpin its success will be critical to improve its clinical efficacy, safety and usability. Furthermore, a deeper understanding of this may allow us to expose FMT's full potential as a therapeutic tool for other disease states. This review will explore the current understanding of the mechanisms underlying the efficacy of FMT across a variety of diseases.}, }
@article {pmid32948430, year = {2020}, author = {Demcsák, A and Soós, A and Kincses, L and Capunge, I and Minkov, G and Kovacheva-Slavova, M and Nakov, R and Wu, D and Huang, W and Xia, Q and Deng, L and Hollenbach, M and Schneider, A and Hirth, M and Ioannidis, O and Vincze, &#xc1; and Bajor, J and Sarlós, P and Czakó, L and Illés, D and Izbéki, F and Gajdán, L and Papp, M and Hamvas, J and Varga, M and Kanizsai, P and Bóna, E and Mikó, A and Váncsa, S and Juhász, MF and Ocskay, K and Darvasi, E and Miklós, E and Erőss, B and Szentesi, A and Párniczky, A and Casadei, R and Ricci, C and Ingaldi, C and Mastrangelo, L and Jovine, E and Cennamo, V and Marino, MV and Barauskas, G and Ignatavicius, P and Pelaez-Luna, M and Rios, AS and Turcan, S and Tcaciuc, E and Małecka-Panas, E and Zatorski, H and Nunes, V and Gomes, A and Gonçalves, TC and Freitas, M and Constantino, J and Sá, M and Pereira, J and Mateescu, B and Constantinescu, G and Sandru, V and Negoi, I and Ciubotaru, C and Negoita, V and Bunduc, S and Gheorghe, C and Barbu, S and Tantau, A and Tantau, M and Dumitru, E and Suceveanu, AI and Tocia, C and Gherbon, A and Litvin, A and Shirinskaya, N and Rabotyagova, Y and Bezmarevic, M and Hegyi, PJ and Han, J and Rodriguez-Oballe, JA and Salas, IM and Comas, EP and Garcia, DI and Cuadrado, AJ and Castiñeira, AQ and Chang, YT and Chang, MC and Kchaou, A and Tlili, A and Kacar, S and Gökbulut, V and Duman, D and Kani, HT and Altintas, E and Chooklin, S and Chuklin, S and Gougol, A and Papachristou, G and Hegyi, P}, title = {Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {20}, number = {7}, pages = {1323-1331}, doi = {10.1016/j.pan.2020.08.009}, pmid = {32948430}, issn = {1424-3911}, mesh = {Acute Disease ; Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile ; Cohort Studies ; Enterocolitis, Pseudomembranous/complications/mortality ; Feces/microbiology ; Female ; Gastrointestinal Hemorrhage/*drug therapy/*etiology/mortality ; Hospitalization ; Humans ; Infections/*complications/mortality ; Male ; Middle Aged ; Pancreatitis/*complications/*drug therapy/mortality ; Proton Pump Inhibitors/*adverse effects/therapeutic use ; Retrospective Studies ; Risk Factors ; Surveys and Questionnaires ; Treatment Outcome ; }, abstract = {BACKGROUND: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP.<br><br>METHODS: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018.<br><br>RESULTS: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality.<br><br>CONCLUSIONS: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.}, }
@article {pmid32946509, year = {2020}, author = {Caldeira, LF and Borba, HH and Tonin, FS and Wiens, A and Fernandez-Llimos, F and Pontarolo, R}, title = {Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {15}, number = {9}, pages = {e0238910}, pmid = {32946509}, issn = {1932-6203}, mesh = {Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Inflammatory Bowel Diseases/*therapy ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {OBJECTIVES: Current evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease.<br><br>METHODS: Systematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted.<br><br>RESULTS: Sixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn's disease patients seemed to benefit more from the procedure.<br><br>CONCLUSIONS: The comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn's disease.}, }
@article {pmid32945066, year = {2021}, author = {El-Salhy, M and Valeur, J and Hausken, T and Gunnar Hatlebakk, J}, title = {Changes in fecal short-chain fatty acids following fecal microbiota transplantation in patients with irritable bowel syndrome.}, journal = {Neurogastroenterology and motility}, volume = {33}, number = {2}, pages = {e13983}, pmid = {32945066}, issn = {1365-2982}, mesh = {Adult ; Double-Blind Method ; *Fatty Acids, Volatile ; Fecal Microbiota Transplantation/*methods ; Feces/*chemistry ; Female ; Humans ; Irritable Bowel Syndrome/*therapy ; Male ; Middle Aged ; }, abstract = {BACKGROUND: Short-chain fatty acids (SCFAs) may play a role in the pathophysiology of irritable bowel syndrome (IBS). This study analyzed fecal SCFAs after performing fecal microbiota transplantation (FMT) in the IBS patients who were included in our previous study of the efficacy of FMT.<br><br>METHODS: This study included 142 of the 164 IBS patients who participated in our previous study. They were belonging to three groups: placebo (own feces), 30-g (superdonor feces), and 60-g (superdonor feces) FMT. The patients completed the IBS Severity Scoring System (IBS-SSS) Birmingham IBS Symptom, Fatigue Assessment Scale (FAS), the IBS Quality of Life (IBS-QoL) and Short-Form Nepean Dyspepsia Index (SF-NDI) questionnaires and delivered fecal samples at the baseline and 1&#xa0;month after FMT. The SCFA levels were determined by vacuum distillation followed by gas chromatography.<br><br>KEY RESULTS: The fecal butyric acid level was significantly increased after FMT in both the 30-g and 60-g groups (both P&#xa0;&#x2264;&#xa0;0.001). In the 60-g group, the levels of total SCFAs and isobutyric, isovaleric, and valeric acids increased after FMT. Butyric acid levels in the responders in both the 30-g and 60-g FMT groups were significantly inversely correlated with IBS-SSS and FAS scores (P&#xa0;=&#xa0;0.001, r&#xa0;=&#xa0;-0.3 and P = 0.0001. r=- 0.3, respectively). There were no differences in the SCFA levels in the placebo group after FMT.<br><br>CONCLUSION AND INFERENCES: FMT increases the fecal SCFA levels in IBS patients. The increase in the butyric acid level is inversely correlated with symptoms in IBS patients following FMT, suggesting that SCFAs might play a role in the pathophysiology of IBS. www.clini&#x200b;caltr&#x200b;ials.gov (NCT03822299).}, }
@article {pmid32944218, year = {2020}, author = {Sima, Y and Chen, Y}, title = {MSC-based therapy in female pelvic floor disorders.}, journal = {Cell &amp; bioscience}, volume = {10}, number = {}, pages = {104}, pmid = {32944218}, issn = {2045-3701}, abstract = {Mesenchymal stem cells (MSCs), also referred to as multipotent stromal cells or mesenchymal stromal cells, are present in multiple tissues and capable of differentiating into diverse cell lineages, holding a great promise in developing cell-based therapy for a wide range of conditions. Pelvic floor disorders (PFDs) is a common degenerative disease in women and may diminish a woman's quality of life at any age. Since the treatments for this disease are limited by the high rates of recurrence and surgical complications, seeking an ideal therapy in the restoration of pelvic floor function is an urgent issue at present. Herein, we summarize the cell sources of MSCs used for PFDs and discuss the potential mechanisms of MSCs in treating PFDs. Specifically, we also provide a comprehensive review of current preclinical and clinical trials dedicated to investigating MSC-based therapy for PFDs. The novel therapy has presented promising therapeutic effects which include relieving the symptoms of urinary or fecal incontinence, improving the biological properties of implanted meshes and promoting the injured tissue repair. Nevertheless, MSC-based therapies for PFDs are still experimental and the unstated issues on their safety and efficacy should be carefully addressed before their clinical applications.}, }
@article {pmid32943612, year = {2020}, author = {Xie, Z and Jiang, H and Liu, W and Zhang, X and Chen, D and Sun, S and Zhou, C and Liu, J and Bao, S and Wang, X and Zhang, Y and Li, J and Hu, L and Li, J}, title = {The triterpenoid sapogenin (2α-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling.}, journal = {Cell death &amp; disease}, volume = {11}, number = {9}, pages = {770}, pmid = {32943612}, issn = {2041-4889}, mesh = {Animals ; Diet, High-Fat ; Drug Design ; Gastrointestinal Microbiome/*drug effects ; Glucagon/metabolism ; Glucagon-Like Peptide 1/*metabolism ; Gynostemma/metabolism ; Intestines/*drug effects ; Male ; Metabolic Syndrome/*drug therapy ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Plant Extracts/metabolism ; RNA, Ribosomal, 16S/metabolism ; RNA-Binding Proteins/*metabolism ; Taurocholic Acid/*analogs &amp; derivatives/chemistry ; }, abstract = {Gypenosides, extracts of Gynostemma yixingense, have been traditionally prescribed to improve metabolic syndrome in Asian folk and local traditional medicine hospitals. However, the mechanism of its action remains unclarified. In this work, our results indicated that chronic administration of 2α-OH-protopanoxadiol (GP2), a metabolite of gypenosides in vivo, protected mice from high-fat diet-induced obesity and improved glucose tolerance by improving intestinal L-cell function. Mechanistically, GP2 treatment inhibited the enzymatic activity of bile salt hydrolase and modulated the proportions of the gut microbiota, which led to an increase in the accumulation of tauro-β-muricholic acid (TβMCA) in the intestine. TβMCA induced GLP-1 production and secretion by reducing the transcriptional activity of nuclear receptor farnesoid X receptor (FXR). Transplantation of GP2-remodelled fecal microbiota into antibiotic-treated mice also increased the intestinal TβMCA content and improved intestinal L-cell function. These findings demonstrate that GP2 ameliorates metabolic syndrome at least partly through the intestinal FXR/GLP-1 axis via gut microbiota remodelling and also suggest that GP2 may serve as a promising oral therapeutic agent for metabolic syndrome.}, }
@article {pmid32942889, year = {2020}, author = {Stebel, R and Vojtilová, L and Husa, P}, title = {[Clostridium difficile Infection: an update on treatment and prevention].}, journal = {Vnitrni lekarstvi}, volume = {66}, number = {2}, pages = {58-62}, pmid = {32942889}, issn = {0042-773X}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/epidemiology/prevention &amp; control ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Disruption of the colonic microflora is one of the most significant adverse effects of antibiotic (ATB) therapy. Excessive multiplication of toxigenic Clostridioides difficile strains is responsible for about 20 % of cases of post-antibiotic diarrhoea. The global trend of Clostridium colitis incidence, severity, mortality and in particular therapeutic failure keeps rising. At the Department of Infectious Diseases we work on long-term monitoring of the most important colitis-associated risk factors and evaluation of individual therapeutic and preventive procedures (selective ATB therapy, faecal bacteriotherapy). A diligent analysis of risk factors and knowledge of pathogenesis are a prerequisite to practical implementation of effective and rational precautions to curb spreading of this illness. In the future, we anticipate increased use of fecal microbiota transplant, improvements in faecal transplant administration, wider use of probiotics and selective ATBs and further introduction of passive and active immunization into practice.}, }
@article {pmid32942689, year = {2020}, author = {Nowland, TL and Torok, VA and Low, WY and Plush, KJ and Barton, MD and Kirkwood, RN}, title = {A Single Faecal Microbiota Transplantation Altered the Microbiota of Weaned Pigs.}, journal = {Life (Basel, Switzerland)}, volume = {10}, number = {9}, pages = {}, pmid = {32942689}, issn = {2075-1729}, abstract = {Weaning is a stressful time for piglets, often leading to weight loss and is associated with increased morbidity and mortality. A leading cause for these post-weaning problems is enteric dysbiosis and methods to improve piglet health at this crucial developmental stage are needed. This study aimed to determine whether an enteric dysbiosis caused by weaning could be corrected via a faecal microbiota transplantation (FMT) from healthy piglets from a previous wean. Two or four focal piglets per litter were assigned to one of two treatments; FMT two days post weaning (n = 21; FMT) or a control which received saline two days post weaning (n = 21; CON). FMT consisted of homogenised donor faeces administered orally at 3 mL/kg. Weaning occurred at 18 days of age and weights and faecal samples were collected on days 18, 20, 24 and 35. 16S rRNA amplicon analysis was used to assess the faecal microbiota of piglets. FMT increased Shannon's diversity post weaning (p < 0.001) and reduced the scratch score observed at 24 days of age (p < 0.001). The bacterial populations significantly differed in composition at each taxonomic level. In FMT pigs, significant increases in potentially pathogenic Escherichia coli were observed. However, increases in beneficial bacteria Lactobacillus mucosae and genera Fibrobacteres and Bacteroidetes were also observed in FMT treated animals. To our knowledge, this is the first study to observe a significant effect on piglet faecal microbiota following a single FMT administered post weaning. Therefore, FMT post weaning can potentially alleviate enteric dysbiosis.}, }
@article {pmid32939928, year = {2020}, author = {Masetti, R and Zama, D and Leardini, D and Muratore, E and Turroni, S and Prete, A and Brigidi, P and Pession, A}, title = {The gut microbiome in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.}, journal = {Pediatric blood &amp; cancer}, volume = {67}, number = {12}, pages = {e28711}, doi = {10.1002/pbc.28711}, pmid = {32939928}, issn = {1545-5017}, mesh = {Gastrointestinal Microbiome/*immunology ; Graft vs Host Disease/*etiology/pathology ; Hematologic Neoplasms/*therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Transplantation, Homologous ; }, abstract = {The gut microbiome (GM) has been associated with different clinical outcomes in the context of allogeneic hematopoietic stem cell transplantation (HSCT). Large multicenter cohort studies in adults have found significant correlations with overall survival, relapse, and incidence of complications. Moreover, GM is already a promising target for therapeutic interventions. However, few data are available in children, a population presenting unique features and challenges. During childhood, the GM evolves rapidly with large structural fluctuations, alongside with the maturation of the immune system. Furthermore, the HSCT procedure presents significant differences in children. These considerations underline the importance of a specific focus on the pediatric setting, and the role of GM and its age-dependent trajectory in influencing the immunity reconstitution and clinical outcomes. This review provides a comprehensive overview of the available evidence in the field of GM and pediatric HSCT, highlighting age-specific issues and discussing GM-based therapeutic approaches.}, }
@article {pmid32934044, year = {2020}, author = {Woodhouse, C and Singanayagam, A and Patel, VC}, title = {Modulating the gut-liver axis and the pivotal role of the faecal microbiome in cirrhosis.}, journal = {Clinical medicine (London, England)}, volume = {20}, number = {5}, pages = {493-500}, pmid = {32934044}, issn = {1473-4893}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis ; *Microbiota ; }, abstract = {Cirrhosis is associated with intestinal dysbiosis, with specific alterations in the gut microbiota linked to particular aetiologies and manifestations of the disease. We review the role of the gut microbiome and the importance of the intestinal barrier in cirrhosis, provide an overview of the terminology and techniques relevant to this emerging area, and discuss the latest developments in therapies targeting the gut-liver axis.}, }
@article {pmid32929373, year = {2020}, author = {Wu, J and Wei, Z and Cheng, P and Qian, C and Xu, F and Yang, Y and Wang, A and Chen, W and Sun, Z and Lu, Y}, title = {Rhein modulates host purine metabolism in intestine through gut microbiota and ameliorates experimental colitis.}, journal = {Theranostics}, volume = {10}, number = {23}, pages = {10665-10679}, pmid = {32929373}, issn = {1838-7640}, mesh = {Animals ; Anthraquinones/*pharmacology/therapeutic use ; Colitis, Ulcerative/chemically induced/*drug therapy/microbiology/pathology ; Dextran Sulfate/administration &amp; dosage/toxicity ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Intestinal Mucosa/*drug effects/microbiology/pathology ; Lactobacillus/drug effects ; Male ; Metabolic Networks and Pathways/drug effects ; Mice ; Probiotics ; Purines/metabolism ; Uric Acid/analysis/metabolism ; }, abstract = {Background: Gut microbiota, which plays a crucial role in inflammatory bowel diseases (IBD), might have therapeutic benefits for ulcerative colitis or Crohn's disease. Targeting gut microbiota represents a new treatment strategy for IBD patients. Rhein is one of the main components of rhubarb and exhibits poor oral bioavailability but still exerts anti-inflammatory effects in some diseases. Therefore, we investigated the effect of rhein on colitis and studied its possible mechanisms. Methods: The chronic mouse colitis model was induced by four rounds of 2% dextran sulfate sodium (DSS) treatment. The mice were treated with 50 mg/kg and 100 mg/kg rhein daily, body weight, colon length, histological score, inflammatory cytokines in serum or intestine, and fecal lipocalin 2 concentration were determined. Th17 cell, Th1 cell and Th2 cell infiltration in the mesenteric lymph node were analyzed by flow cytometry. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 4.0. We also assessed intestinal barrier permeability and performed 16s rDNA sequencing. Lactobacillus sp. was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate the contribution of gut microbiota. Results: Rhein could significantly alleviate DSS-induced chronic colitis. Uric acid was identified as a crucial modulator of colitis and rhein treatment led to decreased uric acid levels. We determined that rhein changed purine metabolism indirectly, while the probiotic Lactobacillus was involved in the regulation of host metabolism. Uric acid resulted in a worsened intestinal barrier, which could be rescued by rhein. We further confirmed that rhein-treated gut microbiota was sufficient to relieve DSS-induced colitis by FMT. Conclusion: We showed that rhein could modulate gut microbiota, which indirectly changed purine metabolism in the intestine and subsequently alleviated colitis. Our study has identified a new approach to the clinical treatment of colitis.}, }
@article {pmid32925627, year = {2020}, author = {Jeney, SES and Lane, F and Oliver, A and Whiteson, K and Dutta, S}, title = {Fecal Microbiota Transplantation for the Treatment of Refractory Recurrent Urinary Tract Infection.}, journal = {Obstetrics and gynecology}, volume = {136}, number = {4}, pages = {771-773}, pmid = {32925627}, issn = {1873-233X}, support = {R21 AI149354/AI/NIAID NIH HHS/United States ; T32 AI141346/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Drug Resistance, Bacterial ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Recurrence ; Secondary Prevention/*methods ; Treatment Outcome ; *Urinary Tract Infections/microbiology/physiopathology/prevention &amp; control ; }, abstract = {Fecal microbiota transplantation may reduce urinary tract infection by altering gut microbiome.}, }
@article {pmid32925094, year = {2020}, author = {West, CL and Mao, YK and Delungahawatta, T and Amin, JY and Farhin, S and McQuade, RM and Diwakarla, S and Pustovit, R and Stanisz, AM and Bienenstock, J and Barbut, D and Zasloff, M and Furness, JB and Kunze, WA}, title = {Squalamine Restores the Function of the Enteric Nervous System in Mouse Models of Parkinson's Disease.}, journal = {Journal of Parkinson's disease}, volume = {10}, number = {4}, pages = {1477-1491}, doi = {10.3233/JPD-202076}, pmid = {32925094}, issn = {1877-718X}, mesh = {Animals ; Cholestanols/administration &amp; dosage/pharmacology ; Constipation/*drug therapy/etiology ; Disease Models, Animal ; Electrophysiological Phenomena/*drug effects ; Enteric Nervous System/*drug effects ; Gastrointestinal Motility/*drug effects ; Jejunum/innervation ; Mice ; Mice, Transgenic ; Mutant Proteins ; Myenteric Plexus/*drug effects ; Neurons, Afferent/cytology/*drug effects ; Parkinson Disease/*complications ; Patch-Clamp Techniques ; Vagus Nerve/*drug effects ; alpha-Synuclein/metabolism ; }, abstract = {BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder thought to be caused by accumulation of α-synuclein (α-syn) within the brain, autonomic nerves, and the enteric nervous system (ENS). Involvement of the ENS in PD often precedes the onset of the classic motor signs of PD by many years at a time when severe constipation represents a major morbidity. Studies conducted in vitro and in vivo, have shown that squalamine, a zwitterionic amphipathic aminosterol, originally isolated from the liver of the dogfish shark, effectively displaces membrane-bound α-syn.<br><br>OBJECTIVE: Here we explore the electrophysiological effect of squalamine on the gastrointestinal (GI) tract of mouse models of PD engineered to express the highly aggregating A53T human &#x3b1;-syn mutant.<br><br>METHODS: GI motility and in vivo response to oral squalamine in PD model mice and controls were assessed using an in vitro tissue motility protocol and via fecal pellet output. Vagal afferent response to squalamine was measured using extracellular mesenteric nerve recordings from the jejunum. Whole cell patch clamp was performed to measure response to squalamine in the myenteric plexus.<br><br>RESULTS: Squalamine effectively restores disordered colonic motility in vivo and within minutes of local application to the bowel. We show that topical squalamine exposure to intrinsic primary afferent neurons (IPANs) of the ENS rapidly restores excitability.<br><br>CONCLUSION: These observations may help to explain how squalamine may promote gut propulsive activity through local effects on IPANs in the ENS, and further support its possible utility in the treatment of constipation in patients with PD.}, }
@article {pmid32924908, year = {2020}, author = {Liu, Y and Qin, S and Feng, Y and Song, Y and Lv, N and Liu, F and Zhang, X and Wang, S and Wei, Y and Li, S and Su, S and Zhang, W and Xue, Y and Hao, Y and Zhu, B and Ma, J and Yang, H}, title = {Perturbations of gut microbiota in gestational diabetes mellitus patients induce hyperglycemia in germ-free mice.}, journal = {Journal of developmental origins of health and disease}, volume = {11}, number = {6}, pages = {580-588}, doi = {10.1017/S2040174420000768}, pmid = {32924908}, issn = {2040-1752}, mesh = {Adult ; Animals ; Blood Glucose/analysis/metabolism ; Case-Control Studies ; Diabetes, Gestational/blood/diagnosis/*microbiology/physiopathology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Hyperglycemia/blood/diagnosis/*microbiology/physiopathology ; Mice ; Pregnancy ; Prenatal Exposure Delayed Effects/blood/diagnosis/*microbiology/physiopathology ; }, abstract = {Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.}, }
@article {pmid32923252, year = {2020}, author = {Lin, Z and Iqbal, Z and Ortiz, JF and Khan, SA and Jahan, N}, title = {Fecal Microbiota Transplantation in Recurrent Clostridium Difficile Infection: Is it Superior to Other Conventional Methods?.}, journal = {Cureus}, volume = {12}, number = {8}, pages = {e9653}, pmid = {32923252}, issn = {2168-8184}, abstract = {Clostridium difficile (C. difficile) is a gram-positive species of spore-forming bacteria. C. difficile infection (CDI) is one of the most common hospital-acquired infections in the United States, mainly caused by the use of recent antibiotics that leads to intestinal dysbiosis. Recurrent C. difficile infection (rCDI) often occurs after the successful treatment of CDI. Approximately, 30% of patients experience a clinical recurrence of prior symptoms within eight weeks of antibiotic cessation. This present literature review covers the current pathophysiology of CDI, risk factors for infection, diagnostic methods, several treatment modalities, and the potential use of fecal microbial transplant (FMT) for patients with multiple recurrent CDIs. Recent studies have focused on FMT, with an efficacy rate of nearly 90% in multiple recurrent CDI settings. Despite its efficacy, it is not commonly used as first-line treatment. More studies are needed to establish this therapy as the first option in patients with rCDI.}, }
@article {pmid32922400, year = {2020}, author = {Kreft, L and Hoffmann, C and Ohnmacht, C}, title = {Therapeutic Potential of the Intestinal Microbiota for Immunomodulation of Food Allergies.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1853}, pmid = {32922400}, issn = {1664-3224}, mesh = {Animals ; Food Hypersensitivity/*immunology ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunomodulation/*immunology ; Mice ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Food allergy is an atopic disease that is caused by the immune system targeting harmless food antigens that can result in life-threatening anaphylaxis. As humans and microbes have co-evolved, inevitably commensal microbes have a tremendous impact on our health. As such, the gut with its enormous microbial richness reflects a highly tolerogenic environment at steady state, in which immune cells are educated to react in a well-calibrated manner to food and microbial antigens. Recent evidence indicates that the susceptibility to food allergy is critically linked to microbial dysbiosis and can be transmitted by microbial transfer from humans to mice. Experimental work and epidemiological studies further point toward a critical time window in early childhood during which the immune system is imprinted by microbial colonization. Particularly, Foxp3-expressing regulatory T cells turn out to be key players, acting as rheostats for controlling the magnitude of food allergic reactions. An increasing number of bacterial metabolites has recently been shown to regulate directly or indirectly the differentiation of peripherally induced Tregs, most of which co-express the RAR-related orphan receptor gamma t (RORγt). Genetic ablation provided additional direct evidence for the importance of RORγt+ Tregs in food allergy. Future strategies for the stratification of food allergic patients with the aim to manipulate the intestinal microbiota by means of fecal transplantation efforts, pre- or probiotic regimens or for boosting oral immunotherapy may improve diagnosis and therapy. In this review some of the key underlying mechanisms are summarized and future directions for potential microbial therapy are explored.}, }
@article {pmid32920548, year = {2020}, author = {Zhang, L and Zhou, W and Zhan, L and Hou, S and Zhao, C and Bi, T and Lu, X}, title = {Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus.}, journal = {Aging}, volume = {12}, number = {17}, pages = {17480-17502}, pmid = {32920548}, issn = {1945-4589}, abstract = {Obesity is one of the susceptibility factors for type 2 diabetes (T2DM), both of which could accelerate the aging of the body and bring many hazards. A causal relationship is present between intestinal microbiota and body metabolism, but how the microbiota play a role in the progression of obesity to T2DM has not been elucidated. In this study, we transplanted healthy or obese-T2DM intestinal microbiota to ZDF and LZ rats, and used 16S rRNA and targeted metabonomics to evaluate the directional effect of the microbiota on the susceptibility of obese rats to T2DM. The glycolipid metabolism phenotype could be changed bidirectionally in obese rats instead of in lean ones. One possible mechanism is that the microbiota and metabolites alter the structure of the intestinal tract, and improve insulin and leptin resistance through JAK2 / IRS / Akt pathway. It is worth noting that 7 genera, such as Lactobacillus, Clostridium and Roche, can regulate 15 metabolites, such as 3-indolpropionic acid, acetic acid and docosahexaenoic acid, and have a significant improvement on glycolipid metabolism phenotype. Attention to intestinal homeostasis may be the key to controlling obesity and preventing T2DM.}, }
@article {pmid32920061, year = {2020}, author = {Seong, H and Lee, SK and Cheon, JH and Yong, DE and Koh, H and Kang, YK and Jeong, WY and Lee, WJ and Sohn, Y and Cho, Y and Hyun, JH and Baek, YJ and Kim, MH and Kim, JH and Ahn, JY and Ku, NS and Jeong, SJ and Yeom, JS and Cho, MS and Lee, JH and Kim, BY and Choi, JY}, title = {Fecal Microbiota Transplantation for multidrug-resistant organism: Efficacy and Response prediction.}, journal = {The Journal of infection}, volume = {81}, number = {5}, pages = {719-725}, doi = {10.1016/j.jinf.2020.09.003}, pmid = {32920061}, issn = {1532-2742}, mesh = {Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation ; Feces ; Firmicutes ; *Gastrointestinal Microbiome ; Humans ; *Vancomycin-Resistant Enterococci ; }, abstract = {OBJECTIVES: The increasing prevalence of multidrug-resistant microorganisms (MDRO) is increasing the frequency of poor clinical outcomes, prolonging hospitalizations, and raising healthcare costs. This study evaluated the eradication efficacy of fecal microbiota transplantation (FMT) and identified microbial and functional biomarkers of MDRO decolonization.<br><br>METHODS: Fecal solution obtained from healthy unrelated donors was infused in the participants' guts which had been colonized with carbapenemase-producing enterobacteriacea (CPE), vancomycin-resistant enterococci (VRE), or both CPE and VRE. Fecal samples from recipients were collected and microbiome changes before and after FMT were assessed.<br><br>RESULTS: Twenty-four (68.6%) out of 35 patients were decolonized within one year of receiving FMT. Multivariate analysis showed that FMT (FMT: hazard ratio (HR)&#x202f;=&#x202f;5.343, 95% confidence interval (CI)&#x202f;=&#x202f;1.877-15.212, p&#x202f;=&#x202f;0.002) and MDRO types (CPE: HR&#x202f;=&#x202f;11.146, 95% CI&#x202f;=&#x202f;2.420-51.340, p&#x202f;=&#x202f;0.002; CPE/VRE: HR&#x202f;=&#x202f;2.948, 95% CI&#x202f;=&#x202f;1.200-7.246, p&#x202f;=&#x202f;0.018; VRE served as the reference) were significant independent factors associated with time to decolonization. Microbiota analysis showed higher richness and biodiversity before FMT resulted in VRE decolonization. The species Clostridium ramosum and the genuses Anaerostipes and Eisenbergiella could serve as taxonomic biomarkers and K02017 could serve as a functional biomarker for VRE clearance.<br><br>CONCLUSION: FMT is an effective way to decolonize MDRO and its effectiveness may be predicted by microbiome analysis.}, }
@article {pmid32917563, year = {2020}, author = {Apartsin, K and Smirnova, V}, title = {Convalescent fecal microbiota transplantation as a possible treatment for COVID-19.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {44}, number = {5}, pages = {e113-e114}, pmid = {32917563}, issn = {2210-741X}, mesh = {*Betacoronavirus ; COVID-19 ; Coronavirus Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Immunization, Passive ; Pandemics ; Pneumonia, Viral/*therapy ; SARS-CoV-2 ; COVID-19 Serotherapy ; }, }
@article {pmid32916306, year = {2020}, author = {Hartstra, AV and Schüppel, V and Imangaliyev, S and Schrantee, A and Prodan, A and Collard, D and Levin, E and Dallinga-Thie, G and Ackermans, MT and Winkelmeijer, M and Havik, SR and Metwaly, A and Lagkouvardos, I and Nier, A and Bergheim, I and Heikenwalder, M and Dunkel, A and Nederveen, AJ and Liebisch, G and Mancano, G and Claus, SP and Benítez-Páez, A and la Fleur, SE and Bergman, JJ and Gerdes, V and Sanz, Y and Booij, J and Kemper, E and Groen, AK and Serlie, MJ and Haller, D and Nieuwdorp, M}, title = {Infusion of donor feces affects the gut-brain axis in humans with metabolic syndrome.}, journal = {Molecular metabolism}, volume = {42}, number = {}, pages = {101076}, pmid = {32916306}, issn = {2212-8778}, mesh = {Aged ; Butyrates/pharmacology ; Cerebral Cortex/metabolism ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Insulin/metabolism ; Insulin Resistance/physiology ; Male ; Metabolic Syndrome/metabolism/*microbiology/*therapy ; Microbiota ; Middle Aged ; Obesity/metabolism ; Serotonin Plasma Membrane Transport Proteins/metabolism ; }, abstract = {OBJECTIVE: Increasing evidence indicates that intestinal microbiota play a role in diverse metabolic processes via intestinal butyrate production. Human bariatric surgery data suggest that the gut-brain axis is also involved in this process, but the underlying mechanisms remain unknown.<br><br>METHODS: We compared the effect of fecal microbiota transfer (FMT) from post-Roux-en-Y gastric bypass (RYGB) donors vs oral butyrate supplementation on ([123]I-FP-CIT-determined) brain dopamine transporter (DAT) and serotonin transporter (SERT) binding as well as stable isotope-determined insulin sensitivity at baseline and after 4 weeks in 24 male and female treatment-na&#xef;ve metabolic syndrome subjects. Plasma metabolites and fecal microbiota were also determined at these time points.<br><br>RESULTS: We observed an increase in brain DAT after donor FMT compared to oral butyrate that reduced this binding. However, no effect on body weight and insulin sensitivity was demonstrated after post-RYGB donor feces transfer in humans with metabolic syndrome. Increases in fecal levels of Bacteroides uniformis were significantly associated with an increase in DAT, whereas increases in Prevotella spp. showed an inverse association. Changes in the plasma metabolites glycine, betaine, methionine, and lysine (associated with the S-adenosylmethionine cycle) were also associated with altered striatal DAT expression.<br><br>CONCLUSIONS: Although more and larger studies are needed, our data suggest a potential gut microbiota-driven modulation of brain dopamine and serotonin transporters in human subjects with obese metabolic syndrome. These data also suggest the presence of a gut-brain axis in humans that can be modulated.<br><br>NTR REGISTRATION: 4488.}, }
@article {pmid32913089, year = {2020}, author = {Wargo, JA}, title = {Modulating gut microbes.}, journal = {Science (New York, N.Y.)}, volume = {369}, number = {6509}, pages = {1302-1303}, doi = {10.1126/science.abc3965}, pmid = {32913089}, issn = {1095-9203}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; }, mesh = {Clostridioides difficile ; Diet ; Dysbiosis/therapy ; Enterocolitis, Pseudomembranous/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/therapy ; Prebiotics/administration &amp; dosage ; }, }
@article {pmid32911536, year = {2020}, author = {Vicente-Dueñas, C and Janssen, S and Oldenburg, M and Auer, F and González-Herrero, I and Casado-García, A and Isidro-Hernández, M and Raboso-Gallego, J and Westhoff, P and Pandyra, AA and Hein, D and Gössling, KL and Alonso-López, D and De Las Rivas, J and Bhatia, S and García-Criado, FJ and García-Cenador, MB and Weber, APM and Köhrer, K and Hauer, J and Fischer, U and Sánchez-García, I and Borkhardt, A}, title = {An intact gut microbiome protects genetically predisposed mice against leukemia.}, journal = {Blood}, volume = {136}, number = {18}, pages = {2003-2017}, pmid = {32911536}, issn = {1528-0020}, mesh = {Animals ; *Disease Susceptibility ; Dysbiosis/*complications ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Leukemia, Experimental/genetics/microbiology/pathology/*prevention &amp; control ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; PAX5 Transcription Factor/*physiology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics/microbiology/pathology/*prevention &amp; control ; }, abstract = {The majority of childhood leukemias are precursor B-cell acute lymphoblastic leukemias (pB-ALLs) caused by a combination of prenatal genetic predispositions and oncogenic events occurring after birth. Although genetic predispositions are frequent in children (>1% to 5%), fewer than 1% of genetically predisposed carriers will develop pB-ALL. Although infectious stimuli are believed to play a major role in leukemogenesis, the critical determinants are not well defined. Here, by using murine models of pB-ALL, we show that microbiome disturbances incurred by antibiotic treatment early in life were sufficient to induce leukemia in genetically predisposed mice, even in the absence of infectious stimuli and independent of T cells. By using V4 and full-length 16S ribosomal RNA sequencing of a series of fecal samples, we found that genetic predisposition to pB-ALL (Pax5 heterozygosity or ETV6-RUNX1 fusion) shaped a distinct gut microbiome. Machine learning accurately (96.8%) predicted genetic predisposition using 40 of 3983 amplicon sequence variants as proxies for bacterial species. Transplantation of either wild-type (WT) or Pax5+/- hematopoietic bone marrow cells into WT recipient mice revealed that the microbiome is shaped and determined in a donor genotype-specific manner. Gas chromatography-mass spectrometry (GC-MS) analyses of sera from WT and Pax5+/- mice demonstrated the presence of a genotype-specific distinct metabolomic profile. Taken together, our data indicate that it is a lack of commensal microbiota rather than the presence of specific bacteria that promotes leukemia in genetically predisposed mice. Future large-scale longitudinal studies are required to determine whether targeted microbiome modification in children predisposed to pB-ALL could become a successful prevention strategy.}, }
@article {pmid32910532, year = {2021}, author = {Dutta, D and Jafri, F and Stuhr, D and Knoll, BM and Lim, SH}, title = {A contemporary review of Clostridioides difficile infections in patients with haematologic diseases.}, journal = {Journal of internal medicine}, volume = {289}, number = {3}, pages = {293-308}, doi = {10.1111/joim.13173}, pmid = {32910532}, issn = {1365-2796}, mesh = {Clostridioides difficile/pathogenicity ; Clostridium Infections/*drug therapy/*etiology ; Gastrointestinal Microbiome ; Hematologic Diseases/*complications ; Hospitalization ; Humans ; Risk Factors ; Virulence ; }, abstract = {Clostridioides (Clostridium) difficile (C. difficile) infection is one of the most common causes of increased morbidity and mortality. Approximately 500 000 C. difficile infections (CDIs) occur each year in the United States, and they result in more than 29 000 deaths. Patients with haematologic diseases are at a higher risk for this infection due to frequent hospitalization and exposure to treatment-associated risk factors. Whilst several currently available antimicrobial agents offer resolution, recurrence of infection remains a major concern. Recent advancement in deciphering C. difficile virulence mechanisms and identification of its allies in contributing to the infection has led to the development of alternative treatment strategies. Here, we will provide a contemporary discussion of how major risk factors in haematologic diseases, such as immunosuppression, chemoradiation, use of antibiotic, proton pump inhibitor and opioid, and deficiency in butyrate and antimicrobial peptides contribute to C. difficile infection. Next, we will highlight different approaches to control and mitigate this infection such as antibiotic stewardship and faecal microbiota transplantation. Finally, we will explore several emerging treatments such as use of pre- and probiotics, immunotherapy and microbiome-sparing agents.}, }
@article {pmid32909356, year = {2020}, author = {Chen, M and Liu, XL and Zhang, YJ and Nie, YZ and Wu, KC and Shi, YQ}, title = {Efficacy and safety of fecal microbiota transplantation by washed preparation in patients with moderate to severely active ulcerative colitis.}, journal = {Journal of digestive diseases}, volume = {21}, number = {11}, pages = {621-628}, pmid = {32909356}, issn = {1751-2980}, support = {81600443//National Natural Science Foundation of China/ ; 81873554//National Natural Science Foundation of China/ ; }, mesh = {Adult ; *Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Remission Induction ; Treatment Outcome ; }, abstract = {OBJECTIVE: We aimed to evaluate the short-term efficacy and safety of fecal microbiota transplantation (FMT) by washed preparation for moderate to severely active UC.<br><br>METHODS: An open-label prospective trial was conducted in an inflammatory bowel disease (IBD) tertiary referral center from April 2016 to March 2018. Patients with moderate to severely active UC were randomly assigned to undergo FMT thrice on day 1, 3 and 5 by nasojejunal tube (NJT) or transendoscopic enteral tubing (TET). The primary end-point was a clinical response at week 2 post-FMT. The secondary end-points were clinical and endoscopic remission at week 12 post-FMT, safety and disease progression.<br><br>RESULTS: Of the nine patients included, 77.8% (7/9) achieved a clinical response at week 2. And 55.6% (5/9) and 33.3% (3/9), respectively, achieved clinical remission and endoscopic remission at week 12. In two patients who had no response to FMT, one switched to anti-tumor necrosis factor-&#x3b1; therapy, and the other underwent a colectomy. FMT was delivered through NJT in 44.4% (4/9) of the patients, while TET was used in 55.6% (5/9). The clinical outcomes did not differ significantly based on the delivery route (P&#x2009;>&#x2009;0.05). Adverse events, all mild and self-limiting, were observed in 33.3% (3/9) of the patients.<br><br>CONCLUSIONS: FMT by washed preparation appears to be a safe and effective adjunct therapy for moderate to severely active UC during a short-term follow-up. The efficacy did not differ significantly between the NJT or TET delivery routes. Further randomized controlled studies are needed to confirm these findings.}, }
@article {pmid32908211, year = {2020}, author = {Park, JC and Im, SH}, title = {Of men in mice: the development and application of a humanized gnotobiotic mouse model for microbiome therapeutics.}, journal = {Experimental &amp; molecular medicine}, volume = {52}, number = {9}, pages = {1383-1396}, pmid = {32908211}, issn = {2092-6413}, mesh = {Animals ; Diet ; *Disease Models, Animal ; Disease Susceptibility/immunology ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Genetic Background ; Genetic Predisposition to Disease ; *Germ-Free Life ; Humans ; Mice ; *Microbiota ; Risk Factors ; Species Specificity ; Translational Research, Biomedical ; Treatment Outcome ; }, abstract = {Considerable evidence points to the critical role of the gut microbiota in physiology and disease. The administration of live microbes as a therapeutic modality is increasingly being considered. However, key questions such as how to identify candidate microorganisms and which preclinical models are relevant to recapitulate human microbiota remain largely unanswered. The establishment of a humanized gnotobiotic mouse model through the fecal microbiota transplantation of human feces into germ-free mice provides an innovative and powerful tool to mimic the human microbial system. However, numerous considerations are required in designing such a model, as various elements, ranging from the factors pertaining to human donors to the mouse genetic background, affect how microbes colonize the gut. Thus, it is critical to match the murine context to that of human donors to provide a continuous and faithful progression of human flora in mice. This is of even greater importance when the need for accuracy and reproducibility across global research groups are taken into account. Here, we review the key factors that affect the formulation of a humanized mouse model representative of the human gut flora and propose several approaches as to how researchers can effectively design such models for clinical relevance.}, }
@article {pmid32906656, year = {2020}, author = {Roussin, L and Prince, N and Perez-Pardo, P and Kraneveld, AD and Rabot, S and Naudon, L}, title = {Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder: Clinical and Preclinical Evidence.}, journal = {Microorganisms}, volume = {8}, number = {9}, pages = {}, pmid = {32906656}, issn = {2076-2607}, support = {H2020-SC1-BHC-03-2018//European Commission/ ; }, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 160 people in the world. Although there is a strong genetic heritability to ASD, it is now accepted that environmental factors can play a role in its onset. As the prevalence of gastrointestinal (GI) symptoms is four-times higher in ASD patients, the potential implication of the gut microbiota in this disorder is being increasingly studied. A disturbed microbiota composition has been demonstrated in ASD patients, accompanied by altered production of bacterial metabolites. Clinical studies as well as preclinical studies conducted in rodents have started to investigate the physiological functions that gut microbiota might disturb and thus underlie the pathophysiology of ASD. The first data support an involvement of the immune system and tryptophan metabolism, both in the gut and central nervous system. In addition, a few clinical studies and a larger number of preclinical studies found that modulation of the microbiota through antibiotic and probiotic treatments, or fecal microbiota transplantation, could improve behavior. Although the understanding of the role of the gut microbiota in the physiopathology of ASD is only in its early stages, the data gathered in this review highlight that this role should be taken in consideration.}, }
@article {pmid32905484, year = {2020}, author = {Cheung, MK and Yue, GGL and Tsui, KY and Gomes, AJ and Kwan, HS and Chiu, PWY and Lau, CBS}, title = {Discovery of an interplay between the gut microbiota and esophageal squamous cell carcinoma in mice.}, journal = {American journal of cancer research}, volume = {10}, number = {8}, pages = {2409-2427}, pmid = {32905484}, issn = {2156-6976}, abstract = {Esophageal squamous cell carcinoma (ESCC) is the main type of esophageal cancer (EC) worldwide, causing half a million deaths each year. Recent evidence has demonstrated the role of the gut microbiota in health and disease. However, our current understanding of the gut microbiome in EC remains scarce. Here, we characterized the gut and esophageal microbiome in a metastatic mouse model of ESCC and examined the functional roles of the gut microbiota in EC development in fecal microbiota transplantation (FMT) experiments. Nude mice intraperitoneally xenografted with human EC-109 cells showed significant alterations in the overall structure, but not alpha diversity, of the gut and esophageal microbiome as compared to naïve control mice. Xenograft of EC cells depleted the order Pasteurellales in the gut microbiome, and enriched multiple predicted metabolic pathways, including those involved in carbohydrate and lipid metabolism, in the esophageal microbiome. FMT of stool from healthy mice to antibiotic-treated xenograft-bearing mice significantly attenuated liver metastasis, suggesting a protective role of the commensal gut microbiota in EC. Moreover, we showed that combination chemotherapy with cisplatin and 5-fluorouracil, and the anti-EC medicinal herb Andrographis paniculata (AP) differentially affected the gut and esophageal microbiome in EC. FMT experiment revealed a reduced anti-metastatic efficacy of AP on liver metastasis in antibiotic-treated xenograft-bearing mice, suggesting a role of the commensal gut microbiota in the anti-metastatic efficacy of the herb. In conclusion, our findings reveal for the first time an interplay between the gut microbiota and EC and provide insights into the treatment strategies for EC.}, }
@article {pmid32904858, year = {2020}, author = {Neres Silva, T and Dábilla, N and Santos Corrêa, T and de Moraes Arantes, A and Souza, M}, title = {Sapovirus detection and quantification in fecal samples from allogeneic hematopoietic stem cell transplant recipients.}, journal = {Virusdisease}, volume = {31}, number = {3}, pages = {374-377}, pmid = {32904858}, issn = {2347-3584}, abstract = {Sapovirus are important agents of acute gastroenteritis (AGE) and they are associated with outbreaks and sporadic cases worldwide. They infect people of all ages, but mainly children, the elderly and immunocompromised individuals are affected. The aim of this study was investigate sapovirus and to determine viral loads in fecal samples from patient undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fecal samples were submitted to extraction of the genetic material using a commercial kit, and RT-qPCR TaqMan was used for sapovirus screening and determination of viral loads, using a standard curve with serial dilutions of a recombinant plasmid. Positive samples were sequence by Sanger method. Sapovirus was detected in one patient, 5.3% (1/19). Viral excretion lasted for 16 days. Viral load varied from 1.73 × 10[6] to 8.97 × 10[6] GC/g. One of the positive samples was characterized as GI.1 genotype. This is the first study to determine sapovirus loads in samples from allo-HSCT and to identify GI.1 genotype in immunocompromised patients.}, }
@article {pmid32901505, year = {2020}, author = {Lozupone, M and D'Urso, F and Piccininni, C and Montagna, M and Sardone, R and Resta, E and Dibello, V and Daniele, A and Giannelli, G and Bellomo, A and Panza, F}, title = {The relationship between epigenetics and microbiota in neuropsychiatric diseases.}, journal = {Epigenomics}, volume = {12}, number = {17}, pages = {1559-1568}, doi = {10.2217/epi-2020-0053}, pmid = {32901505}, issn = {1750-192X}, mesh = {Biomarkers ; *Disease Susceptibility ; *Epigenesis, Genetic ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Humans ; Mental Disorders/*etiology ; *Microbiota ; Probiotics ; }, abstract = {Microbiota might be considered as a pool for environmental epigenetic factors. Evidence is accumulating that environmental exposures - including microbes, diet, drugs - play a role in the pathogenesis of many neuropsychiatric disorders. Underlying mechanisms are complex, involving the sensitive interplay of genetics with epigenetics, neuroinflammation and the innate immune system. Modifications of microbiota affect neurogenesis and the maturation of microglia, influencing social behavior, stress-related responses and fear learning mechanisms. The excitatory neurons in the medial prefrontal cortex appear to play a key role. The mechanisms through which antibiotics administration may modulate microbiota and, therefore, behavior and neuropsychiatric disorders, may be influenced by several variables such as pre-existing gastrointestinal inflammation, the baseline microbiota composition, diet and stress perception. Probiotics, individualized diet, antibiotics and fecal transplantation could positively modulate the effects of epigenetic factors on neuropsychiatric disorders.}, }
@article {pmid32900719, year = {2020}, author = {Benech, N and Leboucher, G and Monard, C and Ferry, T}, title = {Septic shock due to refractory severe clostridioides difficile colitis rapidly resolving after faecal microbiota transplantation.}, journal = {BMJ case reports}, volume = {13}, number = {9}, pages = {}, pmid = {32900719}, issn = {1757-790X}, mesh = {Aged, 80 and over ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Shock, Septic/microbiology/*therapy ; }, }
@article {pmid32899236, year = {2020}, author = {Wang, SC and Chen, YC and Chen, SJ and Lee, CH and Cheng, CM}, title = {Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review.}, journal = {International journal of molecular sciences}, volume = {21}, number = {17}, pages = {}, pmid = {32899236}, issn = {1422-0067}, support = {108-2314-B-695 -002 -//Ministry of Science and Technology, Taiwan/ ; }, mesh = {Alcoholism/*therapy ; Animals ; Behavior, Addictive/*therapy ; *Gastrointestinal Microbiome ; Humans ; Probiotics/*administration &amp; dosage ; }, abstract = {Alcohol addiction is a leading risk factor for personal death and disability. In 2016, alcohol use caused 2.2% of female deaths and 6.8% of male deaths, and disability-adjusted life years (DALYs) were 2.3% in female and 8.9% in male. Individuals with alcohol use disorder are at high risk of anxiety, depression, impaired cognition performance, and illicit drug use and are comorbid with liver disease, such as alcoholic hepatitis and liver cirrhosis, which is a major cause of personal death and disability worldwide. Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. However, the effect of current interventions is limited, and the need for additional interventions is substantial. Alcohol use impairs the intestinal barrier and causes changes to the intestinal permeability as well as the gut microbiota composition. Emerging studies have tried to reveal the role of the gut-brain axis among individuals with alcohol use disorder with or without alcohol liver disease. Bacterial products penetrate the impaired intestinal barrier and cause central inflammation; changes to the gut microbiota impair enterohepatic circulation of bile acids; alcohol abuse causes shortage of vital nutrients such as thiamine. Several studies have suggested that probiotics, through either oral administration or fecal microbiota transplantation, increased intestinal levels of potentially beneficial bacteria such as bifidobacteria and lactobacilli, improving the levels of liver-associated enzymes in patients with mild alcoholic hepatitis, and demonstrating beneficial psychotropic effects on anxiety and depression. In addition to medications for alcohol addiction, gene editing therapy such as clustered regularly interspaced short palindromic repeats (CRISPRs) may be another potential research target. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction.}, }
@article {pmid32898322, year = {2020}, author = {Lai, J and Jiang, J and Zhang, P and Xi, C and Wu, L and Gao, X and Zhang, D and Du, Y and Li, Q and Diao, X and Lu, S and Wang, Z and Song, X and Hu, S}, title = {Gut microbial clues to bipolar disorder: State-of-the-art review of current findings and future directions.}, journal = {Clinical and translational medicine}, volume = {10}, number = {4}, pages = {e146}, pmid = {32898322}, issn = {2001-1326}, support = {81971271//National Natural Science Foundation of China/ ; LQ20H090013//Natural Science Foundation of Zhejiang Province/ ; 2020KY548//Health and Family Planning Commission of Zhejiang Province/ ; }, abstract = {Trillions of microorganisms inhabiting in the human gut play an essential role in maintaining physical and mental health. The connections between gut microbiome and neuropsychiatric diseases have been recently identified. The pathogenesis of bipolar disorder, a spectrum of diseases manifesting with mood and energy fluctuations, also seems to be involved in the bidirectional modulation of the microbiome-gut-brain (MGB) axis. In this review, we briefly introduce the concept of MGB axis, and then focus on the previous findings in human studies associated with bipolar disorder. These studies provided preliminary evidences on the gut microbial alterations in bipolar disorder. Limitations in these studies and future directions in this research field, such as fecal microbiome transplantation and microbiome-targeted therapy, were discussed. A research framework linking gut microbiome to determinants and health-related outcomes in BD was also proposed. Better characterizing and understanding of gut microbial biosignatures in bipolar patients contribute to clarify the etiology of this intractable disease and pave the new way for treatment innovation.}, }
@article {pmid32897773, year = {2020}, author = {Lee, J and Venna, VR and Durgan, DJ and Shi, H and Hudobenko, J and Putluri, N and Petrosino, J and McCullough, LD and Bryan, RM}, title = {Young versus aged microbiota transplants to germ-free mice: increased short-chain fatty acids and improved cognitive performance.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1-14}, pmid = {32897773}, issn = {1949-0984}, support = {R01 NS103592/NS/NINDS NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 HL134838/HL/NHLBI NIH HHS/United States ; RF1 AG058463/AG/NIA NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; }, mesh = {*Aging ; Animals ; Bacteria/classification/growth &amp; development ; Brain/immunology ; *Cognition ; Cognitive Dysfunction/etiology/*therapy ; Cytokines/blood ; Depression ; Fatty Acids, Volatile/analysis/*metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Leukocytes/immunology ; Male ; Memory ; Mice ; Mice, Inbred C57BL ; T-Lymphocyte Subsets/immunology ; }, abstract = {Aging is associated with cognitive decline and decreased concentrations of short-chain fatty acids (SCFAs) in the gut. SCFAs are significant in that they are protective to the gut and other organs. We tested the hypothesis that the aged gut microbiome alone is sufficient to decrease SCFAs in the host and produce cognitive decline. Fecal transplant gavages (FTGs) from aged (18-20 months) or young (2-3 months) male C57BL/6 mice into germ-free male C57BL/6 mice (N = 11 per group) were initiated at ~3 months of age. Fecal samples were collected and behavioral testing was performed over the study period. Bacterial community structures and relative abundances were measured in fecal samples by sequencing the bacterial 16S ribosomal RNA gene. Mice with aged and young microbiomes showed clear differences in bacterial β diversity at 30, 60, and 90 d (P = .001 for each) after FTGs. The fecal SCFAs, acetate, propionate, and butyrate (microbiome effect, P < .01 for each) were decreased in mice with an aged microbiome. Mice with an aged microbiome demonstrated depressive-like behavior, impaired short-term memory, and impaired spatial memory over the 3 months following the initial FTG as assessed by the tail suspension (P = .008), the novel object recognition (P < .001), and the Barnes Maze (P = .030) tests, respectively. We conclude that an aged microbiome alone is sufficient to decrease SCFAs in the host and to produce cognitive decline.}, }
@article {pmid32896201, year = {2020}, author = {Galan-Ros, J and Ramos-Arenas, V and Conesa-Zamora, P}, title = {Predictive values of colon microbiota in the treatment response to colorectal cancer.}, journal = {Pharmacogenomics}, volume = {21}, number = {14}, pages = {1045-1059}, doi = {10.2217/pgs-2020-0044}, pmid = {32896201}, issn = {1744-8042}, mesh = {Animals ; Antineoplastic Agents/*therapeutic use ; Colon/drug effects/*microbiology ; Colorectal Neoplasms/*drug therapy/*microbiology ; Dysbiosis/drug therapy/microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Inflammatory Bowel Diseases/drug therapy/microbiology ; Microbiota/drug effects/*physiology ; }, abstract = {The crosstalk between the colon mucosa and the microbiota represents a complex and delicate equilibrium. Gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer (CRC) are associated with a state of altered microbiota composition known as dysbiosis, which seems to play a causative role in some of these illnesses. Recent reports have shown that the colorectal microbiome is responsible for the response and safety to treatments against CRC, especially immunotherapy, hence opening the possibility to use bacteria as a predictive marker and also as a therapeutic agent. The review objective is to summarize updated reports about the the implication of the colorectal microbiome in the development of CRC, in treatment response and its potential as a therapeutic approach.}, }
@article {pmid32893721, year = {2020}, author = {Martinez-Gili, L and McDonald, JAK and Liu, Z and Kao, D and Allegretti, JR and Monaghan, TM and Barker, GF and Miguéns Blanco, J and Williams, HRT and Holmes, E and Thursz, MR and Marchesi, JR and Mullish, BH}, title = {Understanding the mechanisms of efficacy of fecal microbiota transplant in treating recurrent Clostridioides difficile infection and beyond: the contribution of gut microbial-derived metabolites.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1810531}, pmid = {32893721}, issn = {1949-0984}, support = {21228/VAC_/Versus Arthritis/United Kingdom ; MC_PC_12025/MRC_/Medical Research Council/United Kingdom ; MR/P028225/1/MRC_/Medical Research Council/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; //CIHR/Canada ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Bile Acids and Salts/chemistry/metabolism ; Clostridioides difficile/*physiology ; Clostridium Infections/microbiology/*therapy ; Fatty Acids, Volatile/chemistry/metabolism ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Recurrence ; }, abstract = {Fecal microbiota transplant (FMT) is a highly-effective therapy for recurrent Clostridioides difficile infection (rCDI), and shows promise for certain non-CDI indications. However, at present, its mechanisms of efficacy have remained poorly understood. Recent studies by our laboratory have noted the particular key importance of restoration of gut microbe-metabolite interactions in the ability of FMT to treat rCDI, including the impact of FMT upon short chain fatty acid (SCFAs) and bile acid metabolism. This includes a significant impact of these metabolites upon the life cycle of C. difficile directly, along with potential postulated additional benefits, including effects upon host immune response. In this Addendum, we first present an overview of these recent advancements in this field, and then describe additional novel data from our laboratory on the impact of FMT for rCDI upon several gut microbial-derived metabolites which had not previously been implicated as being of relevance.}, }
@article {pmid32892957, year = {2020}, author = {Thom, RP and McDougle, CJ}, title = {Immune Modulatory Treatments for Autism Spectrum Disorder.}, journal = {Seminars in pediatric neurology}, volume = {35}, number = {}, pages = {100836}, doi = {10.1016/j.spen.2020.100836}, pmid = {32892957}, issn = {1558-0776}, mesh = {Adolescent ; Animals ; Autism Spectrum Disorder/drug therapy/*immunology/*therapy ; Child ; Child, Preschool ; *Fecal Microbiota Transplantation ; Humans ; Immunologic Factors/*pharmacology ; *Stem Cell Transplantation ; }, abstract = {Several lines of evidence from family history studies, immunogenetics, maternal immune activation, neuroinflammation, and systemic inflammation support an immune subtype of autism spectrum disorder (ASD). Current Food and Drug Administration-approved medications for ASD do not address the underlying pathophysiology of ASD, have not consistently been shown to address the core symptoms of ASD, and are currently only approved for treating irritability in children and adolescents. In this article, we review the immune modulatory effects of the 2 currently Food and Drug Administration-approved treatments for ASD. We then provide an overview of current data on emerging treatments for ASD from multiple fields of medicine with immune modulatory effects. Although further research is needed to more clearly establish the efficacy and safety of immune modulatory treatments, early data on repurposing medications used to treat systemic inflammation for ASD demonstrate potential benefit and further research is warranted.}, }
@article {pmid32889369, year = {2020}, author = {Lee, KA and Shaw, HM and Bataille, V and Nathan, P and Spector, TD}, title = {Role of the gut microbiome for cancer patients receiving immunotherapy: Dietary and treatment implications.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {138}, number = {}, pages = {149-155}, doi = {10.1016/j.ejca.2020.07.026}, pmid = {32889369}, issn = {1879-0852}, support = {MR/N01183X/1/MRC_/Medical Research Council/United Kingdom ; MR/N030125/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Anti-Bacterial Agents/adverse effects ; Bacteria/*drug effects/immunology ; *Diet/adverse effects ; Dietary Supplements ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Humans ; Immune Checkpoint Inhibitors/adverse effects/*therapeutic use ; *Immunotherapy/adverse effects ; Neoplasms/*drug therapy/immunology/microbiology ; Nutritional Status ; Proton Pump Inhibitors/adverse effects ; }, abstract = {Immune-checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape for multiple malignancies and the health of the gut microbiome (GM) is strongly linked with therapeutic responses to ICI. This review explores the implications of diet and medication on the GM for patients receiving ICI. Clinical trials are underway to explore the impact of factors such as faecal microbiota transfer, probiotics, prebiotics, bacteria consortia and a number of dietary interventions on patients receiving ICI. Randomised controlled trials are lacking, and inferences are currently based on short-term clinical and observational studies. Antibiotics should be avoided before ICI initiation, and depending on prospective data, future consideration may be given to temporary delay of initiation of non-urgent ICI if patient has had broad spectrum antibiotics within 1 month of planned treatment initiation. Proton pump inhibitor use should be discontinued when not clearly indicated and potential switch to a histamine H2-receptor antagonist considered. Patients should be advised to minimise animal meat intake and maximise plants, aiming to consume ≥30 plant types weekly. A high fibre intake (>30 g/day) has been seen to be beneficial in increasing the chance of ICI response. Fermented foods may have a beneficial effect on the GM and should be introduced where possible. Ideally, all patients should be referred to a nutritionist or dietician with knowledge of GM before commencing ICI.}, }
@article {pmid32884655, year = {2020}, author = {Duplouy, A and Minard, G and Saastamoinen, M}, title = {The gut bacterial community affects immunity but not metabolism in a specialist herbivorous butterfly.}, journal = {Ecology and evolution}, volume = {10}, number = {16}, pages = {8755-8769}, pmid = {32884655}, issn = {2045-7758}, abstract = {Plant tissues often lack essential nutritive elements and may contain a range of secondary toxic compounds. As nutritional imbalance in food intake may affect the performances of herbivores, the latter have evolved a variety of physiological mechanisms to cope with the challenges of digesting their plant-based diet. Some of these strategies involve living in association with symbiotic microbes that promote the digestion and detoxification of plant compounds or supply their host with essential nutrients missing from the plant diet. In Lepidoptera, a growing body of evidence has, however, recently challenged the idea that herbivores are nutritionally dependent on their gut microbial community. It is suggested that many of the herbivorous Lepidopteran species may not host a resident microbial community, but rather a transient one, acquired from their environment and diet. Studies directly testing these hypotheses are however scarce and come from an even more limited number of species.By coupling comparative metabarcoding, immune gene expression, and metabolomics analyses with experimental manipulation of the gut microbial community of prediapause larvae of the Glanville fritillary butterfly (Melitaea cinxia, L.), we tested whether the gut microbial community supports early larval growth and survival, or modulates metabolism or immunity during early stages of development.We successfully altered this microbiota through antibiotic treatments and consecutively restored it through fecal transplants from conspecifics. Our study suggests that although the microbiota is involved in the up-regulation of an antimicrobial peptide, it did not affect the life history traits or the metabolism of early instars larvae.This study confirms the poor impact of the microbiota on diverse life history traits of yet another Lepidoptera species. However, it also suggests that potential eco-evolutionary host-symbiont strategies that take place in the gut of herbivorous butterfly hosts might have been disregarded, particularly how the microbiota may affect the host immune system homeostasis.}, }
@article {pmid32881759, year = {2021}, author = {Mustansir Dawoodbhoy, F and Patel, BK and Patel, K and Bhatia, M and Lee, CN and Moochhala, SM}, title = {Gut Microbiota Dysbiosis as a Target for Improved Post-Surgical Outcomes and Improved Patient Care: A Review of Current Literature.}, journal = {Shock (Augusta, Ga.)}, volume = {55}, number = {4}, pages = {441-454}, doi = {10.1097/SHK.0000000000001654}, pmid = {32881759}, issn = {1540-0514}, mesh = {Dysbiosis/etiology/*prevention &amp; control ; *Gastrointestinal Microbiome ; Humans ; Patient Care/*standards ; Postoperative Complications/etiology/*prevention &amp; control ; Respiratory Distress Syndrome/complications ; Sepsis/complications ; }, abstract = {Critical illness results in significant changes in the human gut microbiota, leading to the breakdown of the intestinal barrier function, which plays a role in the pathogenesis of multiple organ dysfunction. Patients with sepsis/acute respiratory distress syndrome (ARDS) have a profoundly distorted intestinal microbiota rhythm, which plays a considerable role in the development of gut-derived infections and intestinal dysbiosis. Despite recent medical developments, postsurgical complications are associated with a high morbidity and mortality rate. Bacterial translocation, which is the movement of bacteria and bacterial products across the intestinal barrier, was shown to be a mechanism behind sepsis. Current research is focusing on a solution by addressing significant factors that contribute to intestinal dysbiosis, which subsequently leads to multiple organ failure and, thus, mortality. It may, however, be challenging to manipulate the microbiota in critically ill patients for enhanced therapeutic gain. Probiotic manipulation is advantageous for maintaining the gut-barrier defense and for modulating the immune response. Based on available published research, this review aims to address the application of potential strategies in the intensive care unit, supplemented with current therapeutics by the administration of probiotics, prebiotics, and fecal microbiota transplant, to reduce post-surgical complications of sepsis/ARDS in critically ill patients.}, }
@article {pmid32880314, year = {2020}, author = {Labuschaigne, M and Slabbert, M and Budree, S and Hoosien, E and Brink, A and Blockman, M}, title = {The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 3. Stool as a 'drug' or medicine.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {110}, number = {8}, pages = {819-821}, doi = {10.7196/SAMJ.2020.v110i8.15070}, pmid = {32880314}, issn = {2078-5135}, mesh = {Biological Specimen Banks/legislation &amp; jurisprudence ; *Fecal Microbiota Transplantation ; Feces ; Humans ; South Africa ; *Therapeutic Human Experimentation/ethics/legislation &amp; jurisprudence ; Tissue and Organ Procurement/*legislation &amp; jurisprudence ; }, abstract = {The purpose of this article, the last in a series of three exploring the legal framework for the regulation of faecal microbiota transplantation (FMT) in South Africa (SA), is to determine the regulatory framework that applies to microbial-based treatments involving a level of manipulation that exceeds that of basic stool transplantation, e.g. processed FMT-derived products in capsule form. The article highlights the legal requirements for the registration of these products as biological medicines in SA law. Although human stool banks are not regulated in terms of the National Health Act 61 of 2003 (NHA) and regulations, the earlier articles point out that human stool fits the definition of human tissue and human biological material as defined by the NHA. For this reason, stool banks should be considered tissue banks in terms of the NHA and regulations. Healthcare practitioners and researchers involved in FMT banking and transplantation should strive to comply with these regulations in the absence of clear legal direction at present.}, }
@article {pmid32880313, year = {2020}, author = {Labuschaigne, M and Slabbert, M and Budree, S and Hoosien, E and Brink, A and Blockman, M}, title = {The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 2. Human stool as tissue?.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {110}, number = {8}, pages = {816-818}, doi = {10.7196/SAMJ.2020.v110i8.15069}, pmid = {32880313}, issn = {2078-5135}, mesh = {Biological Specimen Banks/legislation &amp; jurisprudence ; *Fecal Microbiota Transplantation ; Feces ; Humans ; South Africa ; Therapeutic Human Experimentation/ethics/legislation &amp; jurisprudence ; Tissue and Organ Procurement/ethics/*legislation &amp; jurisprudence ; }, abstract = {Faecal microbiota transplantation (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infection. The purpose of this article, the second of a series of three articles, is to explore the legal framework governing human FMT in South Africa (SA). FMT involves different modes of administration that require different regulatory considerations. The focus of this article is to explore the legal classification of human stool as tissue in terms of the National Health Act 61 of 2003, as well as the regulation of human stool banks as tissue banks. The article concludes with specific recommendations aimed at improving the current regulatory vacuum relating to the regulation of FMT in SA.}, }
@article {pmid32880312, year = {2020}, author = {Labuschaigne, M and Slabbert, M and Budree, S and Hoosien, E and Brink, A and Blockman, M}, title = {The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 1. A legal vacuum.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {110}, number = {8}, pages = {812-815}, doi = {10.7196/SAMJ.2020.v110i8.14563}, pmid = {32880312}, issn = {2078-5135}, mesh = {Biological Specimen Banks/legislation &amp; jurisprudence ; *Fecal Microbiota Transplantation ; Feces ; Gastrointestinal Microbiome ; Humans ; *Legislation, Medical ; South Africa ; }, abstract = {The legal regulation of faecal microbiota transplantation (FMT) in South Africa (SA) is currently unclear. The purpose of this article, the first of three in a series, is to explore the nature, role and clinical application of FMT in SA in order to determine, from a legal perspective, the appropriate regulatory pathways governing FMT as a procedure that may combine approaches for the treatment of drugs, human tissue for transplantation, or clinical treatment as part of the practice of medicine. FMT has been shown to be a novel, safe and effective treatment for recurrent Clostridioides difficile infection (CDI). Stool banks are instrumental in enabling access to FMT for patients and clinicians and help to catalyse research in the microbiome. However, the regulatory landscape in SA remains unclear. Microbial therapies such as FMT are necessary, especially in a time of rising microbiome-associated inflammatory diseases and increasing resistance to traditional antibiotics. FMT is now considered as part of the standard of care for recurrent CDI overseas, but is currently only being used for research purposes in a minority of clinical cases of CDI in SA. This article, which lays the foundation for consideration of this question in three parts, suggests that the relevant regulatory system would depend on the categorisation of human stool as tissue, the exact composition of the FMT, how it is administered to patients, and the relevant levels of manipulation of the stool for FMT-derived products.}, }
@article {pmid32874052, year = {2020}, author = {Yue, B and Yu, ZL and Lv, C and Geng, XL and Wang, ZT and Dou, W}, title = {Regulation of the intestinal microbiota: An emerging therapeutic strategy for inflammatory bowel disease.}, journal = {World journal of gastroenterology}, volume = {26}, number = {30}, pages = {4378-4393}, pmid = {32874052}, issn = {2219-2840}, mesh = {Animals ; *Colitis ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy ; Intestines ; Mice ; *Microbiota ; }, abstract = {The rapid development of metagenomics, metabolomics, and metatranscriptomics provides novel insights into the intestinal microbiota factors linked to inflammatory bowel disease (IBD). Multiple microorganisms play a role in intestinal health; these include bacteria, fungi, and viruses that exist in a dynamic balance to maintain mucosal homeostasis. Perturbations in the intestinal microbiota disrupt mucosal homeostasis and are closely related to IBD in humans and colitis in mice. Therefore, preventing or correcting the imbalance of microbiota may serve as a novel prevention or treatment strategy for IBD. We review the most recent evidence for direct or indirect interventions targeting intestinal microbiota for treatment of IBD in order to overcome the current limitations of IBD therapies and shed light on personalized treatment options.}, }
@article {pmid32873697, year = {2021}, author = {van den Berg, FF and van Dalen, D and Hyoju, SK and van Santvoort, HC and Besselink, MG and Wiersinga, WJ and Zaborina, O and Boermeester, MA and Alverdy, J}, title = {Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate.}, journal = {Gut}, volume = {70}, number = {5}, pages = {915-927}, pmid = {32873697}, issn = {1468-3288}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 GM062344/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Butyrates/*pharmacology ; *Diet, Western ; Disease Models, Animal ; Disease Progression ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Mice ; Mice, Inbred C57BL ; Pancreatitis, Acute Necrotizing/*diet therapy/microbiology/*mortality ; Phenotype ; }, abstract = {OBJECTIVE: The gut microbiota are the main source of infections in necrotising pancreatitis. We investigated the effect of disruption of the intestinal microbiota by a Western-type diet on mortality and bacterial dissemination in necrotising pancreatitis and its reversal by butyrate supplementation.<br><br>DESIGN: C57BL/6 mice were fed either standard chow or a Western-type diet for 4 weeks and were then subjected to taurocholate-induced necrotising pancreatitis. Blood and pancreas were collected for bacteriology and immune analysis. The cecum microbiota composition of mice was analysed using 16S rRNA gene amplicon sequencing and cecal content metabolites were analysed by targeted (ie, butyrate) and untargeted metabolomics. Prevention of necrotising pancreatitis in this model was compared between faecal microbiota transplantation (FMT) from healthy mice, antibiotic decontamination against Gram-negative bacteria and oral or systemic butyrate administration. Additionally, the faecal microbiota of patients with pancreatitis and healthy subjects were analysed.<br><br>RESULTS: Mortality, systemic inflammation and bacterial dissemination were increased in mice fed Western diet and their gut microbiota were characterised by a loss of diversity, a bloom of Escherichia coli and an altered metabolic profile with butyrate depletion. While antibiotic decontamination decreased mortality, Gram-positive dissemination was increased. Both oral and systemic butyrate supplementation decreased mortality, bacterial dissemination, and reversed the microbiota alterations. Paradoxically, mortality and bacterial dissemination were increased with FMT administration. Finally, patients with acute pancreatitis demonstrated an increase in Proteobacteria and a decrease of butyrate producers compared with healthy subjects.<br><br>CONCLUSION: Butyrate depletion and its repletion appear to play a central role in disease progression towards necrotising pancreatitis.}, }
@article {pmid32871960, year = {2020}, author = {Xue, LJ and Yang, XZ and Tong, Q and Shen, P and Ma, SJ and Wu, SN and Zheng, JL and Wang, HG}, title = {Fecal microbiota transplantation therapy for Parkinson's disease: A preliminary study.}, journal = {Medicine}, volume = {99}, number = {35}, pages = {e22035}, pmid = {32871960}, issn = {1536-5964}, mesh = {Aged ; Colonoscopy ; Fecal Microbiota Transplantation/adverse effects/methods/*statistics &amp; numerical data ; Female ; Humans ; Intubation, Gastrointestinal ; Male ; Middle Aged ; Parkinson Disease/*therapy ; Patient Satisfaction ; Pilot Projects ; Young Adult ; }, abstract = {Imbalances in the gut microbiota mediate the progression of neurodegenerative diseases such as Parkinson's disease (PD). Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for PD. The objective of this study was to assess the efficacy and safety of FMT on PD. Fifteen PD patients were included, 10 of them received FMT via colonoscopy (colonic FMT group) and 5 received FMT via nasal-jejunal tube (nasointestinal FMT group). The score of PSQI, HAMD, HAMA, PDQ-39, NMSQ and UPDRS-III significantly decreased after FMT treatment (all P < .05). Colonic FMT group showed significant improvement and longer maintenance of efficacy compared with nasointestinal FMT (P = .002). Two patients achieved self-satisfying outcomes that last for more than 24 months. However, nasointestinal FMT group had no significant therapeutic effect, although UPDRS-III score slightly reduced. There were no patients were satisfied with nasointestinal FMT for more than 3 months. Among 15 PD patients, there were 5 cases had adverse events (AEs), including diarrhea (2 cases), abdominal pain (2 cases) and flatulence (1 case). These AEs were mild and self-limiting. We conclude that FMT can relieve the motor and non-motor symptoms with acceptable safety in PD. Compared with nasointestinal FMT, colonic FMT seems better and preferable.}, }
@article {pmid32868507, year = {2020}, author = {Caminero, A and Pinto-Sanchez, MI}, title = {Host immune interactions in chronic inflammatory gastrointestinal conditions.}, journal = {Current opinion in gastroenterology}, volume = {36}, number = {6}, pages = {479-484}, doi = {10.1097/MOG.0000000000000673}, pmid = {32868507}, issn = {1531-7056}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: We performed a literature review of the latest studies on the interactions between the host immune system and microbes in chronic intestinal inflammatory conditions.<br><br>RECENT FINDINGS: The mechanisms leading to celiac disease (CeD) and inflammatory bowel disease (IBD), the most common chronic inflammatory gastrointestinal conditions, are complex. The intestinal homeostasis depends on the interactions between the microbiota, the intestinal mucosa and the host immune system. Failure to achieve or maintain equilibrium between a host and its microbiota has the potential to induce chronic conditions with an underlying inflammatory component. Mechanisms by which intestinal microbes trigger inflammation include the alteration of intestinal permeability, activation of the host immune system and digestion of dietary antigens with a consequent repercussion on tolerance to food. Therefore, therapies modulating gut microbiota, including diet, antibiotics, probiotics and faecal transplantation have a potential in CeD and IBD. Probiotics are effective to treat pouchitis and faecal transplant for ulcerative colitis, but the evidence is less clear in Crohn's disease or CeD.<br><br>SUMMARY: Diverse regulatory mechanisms cooperate to maintain intestinal homeostasis, and a breakdown in these pathways may precipitate inflammation. The role of microbiota inducing immune dysfunction and inflammation supports the therapeutic rationale of manipulating microbiota to treat chronic inflammatory conditions.}, }
@article {pmid32866799, year = {2020}, author = {Marcondes Ávila, PR and Fiorot, M and Michels, M and Dominguini, D and Abatti, M and Vieira, A and de Moura, AB and Behenck, JP and Borba, LA and Botelho, MEM and Réus, GZ and Dal-Pizzol, F and Ritter, C}, title = {Effects of microbiota transplantation and the role of the vagus nerve in gut-brain axis in animals subjected to chronic mild stress.}, journal = {Journal of affective disorders}, volume = {277}, number = {}, pages = {410-416}, doi = {10.1016/j.jad.2020.08.013}, pmid = {32866799}, issn = {1573-2517}, mesh = {Animals ; Brain ; *Gastrointestinal Microbiome ; Hypothalamo-Hypophyseal System ; *Microbiota ; Pituitary-Adrenal System ; Vagus Nerve ; }, abstract = {INTRODUCTION: Currently, there is a growing emphasis on the study of intestinal signaling as an influencer in the pathophysiology of neuropsychiatric diseases, and the gut-brain axis is recognized as a communication route through endocrine, immune, and neural pathways (vagus nerve). Studies have shown that diets that modify the microbiota can reduce stress-related behavior and hypothalamic-pituitary-adrenal axis activation. Investigators have used fecal microbiota transplantation (FMT) approaches to demonstrate that stress-related microbiota composition plays a causal role in behavioral changes.<br><br>AIM: We hypothesized that FMT may present immunomodulatory, biochemical, endocrine, cognitive, and behavioral benefits in stress situations and that these changes can be mediated via the vagus nerve.<br><br>METHODS: Animals were subjected to a chronic mild stress (CMS) protocol. In one experiment, animals were divided into five groups: control, control&#xa0;+&#xa0;FMT, control&#xa0;+&#xa0;FMT&#xa0;+&#xa0;CMS, CMS&#xa0;+&#xa0;saline, and CMS&#xa0;+&#xa0;FMT. The animals received FMT, and behavioral tests were performed; cytokine and carbonyl levels were measured. In a second experiment, animals were submitted to vagotomy and divided into two groups: CMS&#xa0;+&#xa0;FMT and CMS&#xa0;+&#xa0;vagotomy&#xa0;+&#xa0;FMT.<br><br>RESULTS: Animals submitted to the CMS protocol or that received FMT from stressed animals showed behavioral changes and changes in neuroactive substances (increased IL-6 and TNF-&#x3b1; levels and carbonyl proteins). The FMT of healthy donors improved the analyzed parameters. In addition, vagotomy influenced beneficial FMT results, confirmed by behavioral testing and protein carbonyl in the hippocampus.<br><br>CONCLUSION: Manipulation of the microbiota reversed the behavioral and biochemical changes induced by the CMS protocol, and the vagus nerve influenced the gut-brain axis response.}, }
@article {pmid32865911, year = {2020}, author = {Mungamuri, SK and Vijayasarathy, K}, title = {Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease Progression.}, journal = {Critical reviews in oncogenesis}, volume = {25}, number = {1}, pages = {57-70}, doi = {10.1615/CritRevOncog.2020035667}, pmid = {32865911}, issn = {0893-9675}, mesh = {Animals ; Choline/metabolism ; Disease Progression ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Non-alcoholic Fatty Liver Disease/*etiology ; Oxidative Stress ; Probiotics/therapeutic use ; }, abstract = {The gut microbiome (GM) is a multifaceted environment wherein nearly 1014 microorganisms play various roles in host immune regulation, intestinal cell proliferation, bone mineralization, xenobiotics metabolism, and protection against pathogens. GM is also strongly coupled with the development and progression of nutrition-related diseases such as nonalcoholic fatty liver disease (NAFLD), wherein the gut-liver axis plays a major role as the gut and liver are functionally and anatomically associated through the portal vein. Dysbiosis causes leaky gut, resulting in the activation of inflammatory processes in the liver. Disruption of the gut barrier enhances microbial infiltration into the sub-mucosae, which through the bloodstream causes harmful microbial metabolites, such as butyrate, long-chain fatty acids, endotoxins, and indole-3-acetic acid, to seep into the liver. In NAFLD patients, these metabolites can lead to the development of nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In this review, we will discuss the important molecular pathways through which various metabolites and other signaling substances released by the GM regulate liver biology, under both physiological and pathological conditions. Finally, we highlight numerous therapeutic attempts, such as probiotics, prebiotics, and fecal microbial transplantation (FMT), to reprogram the gut-liver axis for decreasing liver diseases.}, }
@article {pmid32865119, year = {2020}, author = {Magruder, M and Edusei, E and Zhang, L and Albakry, S and Satlin, MJ and Westblade, LF and Malha, L and Sze, C and Lubetzky, M and Dadhania, DM and Lee, JR}, title = {Gut commensal microbiota and decreased risk for Enterobacteriaceae bacteriuria and urinary tract infection.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1805281}, pmid = {32865119}, issn = {1949-0984}, support = {K23 AI124464/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria/classification/genetics/*isolation &amp; purification ; Child ; DNA, Bacterial/genetics ; Enterobacteriaceae/genetics/*physiology ; Enterobacteriaceae Infections/*microbiology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Postoperative Complications/*microbiology ; RNA, Ribosomal, 16S/genetics ; Transplant Recipients ; Urinary Tract Infections/*microbiology ; Young Adult ; }, abstract = {Urinary tract infection (UTI) is a common complication in kidney transplant recipients and can lead to significant morbidity and mortality. Recent evidence supports a role for the gut as a source for UTIs but little is known about the relationship between gut commensal bacteria and UTI development. We hypothesized that the abundance of gut commensal bacteria is associated with a lower risk of developing bacteriuria and UTIs. We performed gut microbiome profiling using 16S rRNA gene sequencing of the V4-V5 hypervariable region on 510 fecal specimens in 168 kidney transplant recipients. Fifty-one kidney transplant recipients (30%) developed Enterobacteriaceae bacteriuria within the first 6 months after transplantation (Enterobacteriaceae Bacteriuria Group) and 117 did not (No Enterobacteriaceae Bacteriuria Group). The relative abundances of Faecalibacterium and Romboutsia were significantly higher in the fecal specimens from the No Enterobacteriaceae Bacteriuria Group than those from the Enterobacteriaceae Bacteriuria Group (Adjusted P value<.01). The combined relative abundance of Faecalibacterium and Romboutsia was inversely correlated with the relative abundance of Enterobacteriaceae (r = -0.13, P = .003). In a multivariable Cox Regression, a top tercile cutoff of the combined relative abundance of Faecalibacterium and Romboutsia of ≥13.7% was independently associated with a decreased risk for Enterobacteriaceae bacteriuria (hazard ratio 0.3, P = .02) and Enterobacteriaceae UTI (hazard ratio 0.4, P = .09). In conclusion, we identify bacterial taxa associated with decreased risk for Enterobacteriaceae bacteriuria and Enterobacteriaceae UTI in kidney transplant recipients, which supports future studies on modulating the gut microbiota as a novel treatment for preventing UTIs.}, }
@article {pmid32864480, year = {2020}, author = {Zeevenhooven, J and de Bruijn, CMA and Vlieger, A and Nieuwdorp, M and Benninga, MA}, title = {Protocol for a pilot randomised, double-blind, placebo-controlled trial for assessing the feasibility and efficacy of faecal microbiota transplantation in adolescents with refractory irritable bowel syndrome: FAIS Trial.}, journal = {BMJ paediatrics open}, volume = {4}, number = {1}, pages = {e000689}, pmid = {32864480}, issn = {2399-9772}, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic medical condition, in both children and adults. Despite the availability of effective (non)pharmacological treatments, symptoms persist in a significant amount of patients with IBS. Faecal microbiota transplantation (FMT) may be an effective alternative treatment in adolescents with refractory IBS through manipulation of the intestinal microbiota.<br><br>METHODS AND ANALYSIS: This randomised, placebo-controlled single-centre pilot study will assess feasibility and efficacy of FMT in 30 adolescents (16-21 years) with refractory IBS. Patients will be randomly allocated (1:1) to receive two allogeneic (healthy donor) or two autologous (own) faecal infusions at baseline and after 6 weeks. Primary outcomes will assess feasibility, including patient and donor recruitment, adherence and incidence rates of adverse events. To evaluate clinical efficacy, secondary outcomes will include the proportion of patients with at least >50% reduction of their abdominal pain intensity and frequency 12 weeks after the first FMT, and after 6-month and 12-month follow-up. Other outcomes comprise changes in faecal gut microbiota composition, quality of life, depression and anxiety, school or work absenteeism and adequate relief, measured directly after FMTs and after 6 and 12 months of follow-up.<br><br>DISCUSSION: This randomised controlled trial will investigate the feasibility and effectiveness of repetitive FMTs in adolescents with refractory IBS.<br><br>ETHICS AND DISSEMINATION: The study is approved by the Medical Research Ethics Committees AMC (MEC-AMC) in the Netherlands.<br><br>TRIAL REGISTRATION NUMBER: NCT03074227.}, }
@article {pmid33868760, year = {2019}, author = {Li, F and McClain, CJ and Feng, W}, title = {Microbiome dysbiosis and alcoholic liver disease[☆].}, journal = {Liver research (Beijing, China)}, volume = {3}, number = {3-4}, pages = {218-226}, pmid = {33868760}, issn = {2096-2878}, support = {P20 GM113226/GM/NIGMS NIH HHS/United States ; P50 AA024337/AA/NIAAA NIH HHS/United States ; U01 AA026936/AA/NIAAA NIH HHS/United States ; U01 AA026980/AA/NIAAA NIH HHS/United States ; R01 AA023190/AA/NIAAA NIH HHS/United States ; R01 AA023681/AA/NIAAA NIH HHS/United States ; U01 AA022489/AA/NIAAA NIH HHS/United States ; I01 BX002996/BX/BLRD VA/United States ; }, abstract = {Microbiome dysbiosis is strongly associated with alcoholic liver disease (ALD). Recent studies on comprehensive analyses of microbiome compositional and functional changes have begun to uncover the mechanistic relation between microbiome and the pathogenesis of ALD. Importantly, targeting the microbiome has become a potential strategy for the prevention and treatment of ALD. In this review, we summarize the clinical evidence of microbiome dysbiosis in ALD patients, and experimental advances in microbiome and metabolomic functional changes in animals with different species and genetic backgrounds in ALD. We also summarize the studies in humanized intestinal microbiome and fecal microbiota transplantation in mice. We introduce new developments in the studies on the role of the circulating bacterial microbiome, oral bacterial microbiome and fungal microbiome in the development of ALD. We highlight the potential mechanisms by which microbiome dysbiosis contributes to ALD, including short chain fatty acid changes, bile acid metabolism, intestinal barrier function, release of bacterial and fungal products, and inflammation. In addition, we summarize the recent developments targeting the microbiome in prevention and treatment of ALD, including dietary nutrient interference, herbal medicine, antibiotics, anti-fungal agents, probiotics, engineered bacterial therapy, fecal transplantation and oral hygiene. Although recent preclinical studies have advanced our understanding of the microbiome and ALD, clinical studies, especially prospective studies with large samples, are needed to better understand the cause-effect of microbiome dysbiosis in ALD. Identifying new precision-based strategies targeting the microbiome are expected to be developed as more effective therapies in ALD.}, }
@article {pmid33499955, year = {2019}, author = {Blyton, MDJ and Soo, RM and Whisson, D and Marsh, KJ and Pascoe, J and Le Pla, M and Foley, W and Hugenholtz, P and Moore, BD}, title = {Faecal inoculations alter the gastrointestinal microbiome and allow dietary expansion in a wild specialist herbivore, the koala.}, journal = {Animal microbiome}, volume = {1}, number = {1}, pages = {6}, pmid = {33499955}, issn = {2524-4671}, support = {LP140100751//the Australian Research Council/ ; }, abstract = {BACKGROUND: Differences between individuals in their gastrointestinal microbiomes can lead to variation in their ability to persist on particular diets. Koalas are dietary specialists, feeding almost exclusively on Eucalyptus foliage but many individuals will not feed on particular Eucalyptus species that are adequate food for other individuals, even when facing starvation. We undertook a faecal inoculation experiment to test whether a koala's gastrointestinal (GI) microbiome influences their diet. Wild-caught koalas that initially fed on the preferred manna gum (Eucalyptus viminalis) were brought into captivity and orally inoculated with encapsulated material derived from faeces from koalas feeding on either the less preferred messmate (E. obliqua; treatment) or manna gum (control).<br><br>RESULTS: The gastrointestinal microbiomes of wild koalas feeding primarily on manna gum were distinct from those feeding primarily on messmate. We found that the gastrointestinal microbiomes of koalas were unresponsive to dietary changes because the control koalas' GI microbiomes did not change even when the nocturnal koalas were fed exclusively on messmate overnight. We showed that faecal inoculations can assist the GI microbiomes of koalas to change as the treatment koalas' GI microbiomes became more similar to those of wild koalas feeding on messmate. There was no overall difference between the control and treatment koalas in the quantity of messmate they consumed. However, the greater the change in the koalas' GI microbiomes, the more messmate they consumed after the inoculations had established.<br><br>CONCLUSIONS: The results suggest that dietary changes can only lead to changes in the GI microbiomes of koalas if the appropriate microbial species are present, and/or that the koala gastrointestinal microbiome influences diet selection.}, }
@article {pmid34179235, year = {2018}, author = {McLeod, KH and Mason, L and Mariño, E}, title = {Transplantation of Fecal Microbiota Shaped by Diet.}, journal = {Bio-protocol}, volume = {8}, number = {1}, pages = {e2683}, pmid = {34179235}, issn = {2331-8325}, abstract = {Alterations in diet and gut microbial ecology underlie the pathogenesis of type 1 diabetes (T1D). In the non-obese diabetic (NOD) mouse, we found high concentrations of bacterial metabolites acetate and butyrate in blood and faeces correlated with protection from disease. We reconstituted germ free (GF) NOD mice with fecal bacteria from protected NOD mice fed with high acetate- and butyrate-yielding diets, to test whether the transferred gut microbiota protect against the development of T1D. GF NOD mice that received a microbiota shaped by high acetate- but not butyrate-yielding diet showed a marked protection against diabetes. This fecal transplantation assay demonstrated the potential for a dietary technology to reshape the gut microbiota that enables specific bacteria to transfer protection against T1D.}, }
@article {pmid32864024, year = {2020}, author = {Raghu Subramanian, C and Talluri, S and Khan, SU and Katz, JA and Georgetson, M and Sinh, P}, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in Patients With Multiple Comorbidities: Long-Term Safety and Efficacy Results From a Tertiary Care Community Hospital.}, journal = {Gastroenterology research}, volume = {13}, number = {4}, pages = {138-145}, pmid = {32864024}, issn = {1918-2805}, abstract = {BACKGROUND: Cure rates of Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) have been promising. However, there is debate regarding success of FMT in patients with comorbidities.<br><br>METHODS: Electronic chart review was done to collect data on patients who underwent FMT from January 2015 to August 2017. Charts were analyzed in November 2018 with a median follow-up of 25.4 months (interquartile range 20 - 31 months).<br><br>RESULTS: Twenty patients underwent FMT. The primary success rate at our institution was 90% and overall success rate was 100%. Six patients (43%) had FMT failure (two early and four late).<br><br>CONCLUSIONS: This case series is a description of our center's initial experience with FMT for treatment of recurrent CDI. Our high success rate reiterates the efficacy and safety of FMT in this population including patients with comorbidities.}, }
@article {pmid32862830, year = {2020}, author = {Kwak, S and Choi, J and Hink, T and Reske, KA and Blount, K and Jones, C and Bost, MH and Sun, X and Burnham, CD and Dubberke, ER and Dantas, G and , }, title = {Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {125}, pmid = {32862830}, issn = {2049-2618}, support = {U54 CK000162/CK/NCEZID CDC HHS/United States ; }, mesh = {Aged ; Bacteria/*genetics/*isolation &amp; purification ; *Biodiversity ; Double-Blind Method ; Drug Resistance, Microbial/*genetics ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Male ; *Microbiota ; Middle Aged ; }, abstract = {BACKGROUND: Intestinal microbiota restoration can be achieved by complementing a subject's perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic-resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome.<br><br>RESULTS: All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7&#x2009;days post-treatment. However, the microbiome and resistome shifts toward average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel "transplantation index" metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs.<br><br>CONCLUSIONS: Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients' microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product-a proxy for the donor-than an antibiotic perturbed state.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299570 . Registered 19 November 2014 Video Abstract.}, }
@article {pmid32861068, year = {2020}, author = {Zhang, F and Zhang, X and Yu, J and Tan, Y and Guo, P and Wu, C}, title = {The gut microbiota confers the lipid-lowering effect of bitter melon (Momordica charantia L.) In high-fat diet (HFD)-Induced hyperlipidemic mice.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {131}, number = {}, pages = {110667}, doi = {10.1016/j.biopha.2020.110667}, pmid = {32861068}, issn = {1950-6007}, mesh = {Animals ; Diet, High-Fat/*adverse effects ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/drug effects/*physiology ; Hyperlipidemias/*etiology/metabolism/*therapy ; Hypoglycemic Agents/administration &amp; dosage/isolation &amp; purification ; Male ; Mice ; Mice, Inbred C57BL ; *Momordica charantia ; Plant Extracts/*administration &amp; dosage/isolation &amp; purification ; }, abstract = {The bitter melon (Momordica charantia) is a medical food with well-documented hypoglycemic and anti-hyperlipidemic activities. Previous studies showed that the M. charantia fruit (MC) could modulate the gut microbiota, but whether this modulation is essential for MC's pharmacological effects is largely unknown. Here, we assessed the causality of gut microbes in MC-elicited anti-hyperlipidemic effects for the first time. Oral administration of MC significantly prevented hyperlipidemia, but this amelioration substantially diminished when co-treated with antibiotics. Transplantation of gut flora from MC-treated donor mice also significantly decreased serum lipids. The microbiological analysis revealed that MC moderately increased diversity and shifted the overall structure of gut microbiota. It selectively enhanced the relative abundance of short-chain fatty acid (SCFAs)-producing genera and increased fecal SCFAs content. These results demonstrate that M. charantia fruit (MC) may exert an anti-hyperlipidemic effect through modulating gut microbes and increasing SCFAs production.}, }
@article {pmid32860791, year = {2021}, author = {Rinott, E and Youngster, I and Yaskolka Meir, A and Tsaban, G and Zelicha, H and Kaplan, A and Knights, D and Tuohy, K and Fava, F and Scholz, MU and Ziv, O and Rubin, E and Tirosh, A and Rudich, A and Blüher, M and Stumvoll, M and Ceglarek, U and Clement, K and Koren, O and Wang, DD and Hu, FB and Stampfer, MJ and Shai, I}, title = {Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain.}, journal = {Gastroenterology}, volume = {160}, number = {1}, pages = {158-173.e10}, pmid = {32860791}, issn = {1528-0012}, support = {K99 DK119412/DK/NIDDK NIH HHS/United States ; P30 DK046200/DK/NIDDK NIH HHS/United States ; R00 DK119412/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Animals ; Diet, Mediterranean ; Disease Models, Animal ; Exercise ; *Fecal Microbiota Transplantation ; Female ; Humans ; Israel ; Life Style ; Male ; Mice ; Middle Aged ; Obesity/*diet therapy ; Waist Circumference ; *Weight Gain ; Weight Loss ; }, abstract = {BACKGROUND &amp; AIMS: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight-loss phase.<br><br>METHODS: In the DIRECT PLUS (Dietary Intervention Randomized Controlled Trial Polyphenols-Unprocessed) weight-loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to healthy dietary guidelines, Mediterranean diet, and&#xa0;green-Mediterranean diet weight-loss groups. All groups&#xa0;received free gym membership and physical activity guidelines. Both isocaloric Mediterranean groups consumed 28 g/d walnuts (+440 mg/d polyphenols provided). The green-Mediterranean dieters also consumed green tea (3-4 cups/d) and a Wolffia globosa (Mankai strain, 100 g/d) green shake (+800 mg/d polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque, and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight-regain phase (months 6-14). Secondary outcomes were gastrointestinal symptoms, waist circumference, glycemic status, and changes in the gut microbiome, as measured by metagenomic sequencing and 16s ribosomal RNA. We validated the results in a parallel in&#xa0;vivo study of mice specifically fed with Mankai compared with control chow diet.<br><br>RESULTS: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules during the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6-14 (aFMT, 30.4% vs placebo, 40.6%; P&#xa0;= .28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P&#xa0;= .02), but not in the dietary guidelines (P&#xa0;= .57) or Mediterranean diet (P&#xa0;= .64) groups (P for the interaction&#xa0;= .03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89 cm vs placebo, 5.05 cm; P&#xa0;= .01) and insulin rebound (aFMT, -1.46 &#xb1; 3.6 &#x3bc;IU/mL vs placebo, 1.64 &#xb1; 4.7 &#x3bc;IU/mL; P&#xa0;= .04) in the green-Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction&#xa0;= .04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight-loss phase, and to prompt preservation of weight-loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) after the aFMT. In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet-induced regain phase (all, P < .05).<br><br>CONCLUSIONS: Autologous FMT, collected during the weight-loss phase and administrated in the regain phase, might preserve weight loss and glycemic control, and is associated with specific microbiome signatures. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. ClinicalTrials.gov number, NCT03020186.}, }
@article {pmid32860788, year = {2020}, author = {Kong, L and Lloyd-Price, J and Vatanen, T and Seksik, P and Beaugerie, L and Simon, T and Vlamakis, H and Sokol, H and Xavier, RJ}, title = {Linking Strain Engraftment in Fecal Microbiota Transplantation With Maintenance of Remission in Crohn's Disease.}, journal = {Gastroenterology}, volume = {159}, number = {6}, pages = {2193-2202.e5}, pmid = {32860788}, issn = {1528-0012}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 AT009708/AT/NCCIH NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Crohn Disease/immunology/microbiology/*therapy ; Datasets as Topic ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics/immunology ; Haplotypes ; Humans ; Male ; Metagenomics ; Middle Aged ; Molecular Typing ; Phylogeny ; Remission Induction/methods ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: Crohn's disease (CD) is a chronic gastrointestinal disease resulting from the dysfunctional interplay between genetic susceptibility, the immune system, and commensal intestinal microbiota. Emerging evidence suggests that treatment by suppression of the immune response and replacement of the microbiota through fecal microbiota transplantation (FMT) is a promising approach for the treatment of CD.<br><br>METHODS: We obtained stool metagenomes from CD patients in remission and assessed gut microbiome composition before and after FMT at the species and strain levels. Longitudinal follow-up evaluation allowed us to identify the gain, loss, and strain replacement of specific species and link these events to the maintenance of remission in CD.<br><br>RESULTS: We found that FMT had a significant long-term effect on patient microbial compositions, although this was primarily driven by the engraftment of donor species, which remained at low abundance. Thirty-eight percent of FMT-driven changes were strain replacements, emphasizing the importance of detailed profiling methods, such as metagenomics. Several instances of long-term coexistence between donor and patient strains were also observed. Engraftment of some Actinobacteria, and engraftment or loss of Proteobacteria, were related to better disease outcomes in CD patients who received FMT, and transmission of Bacteroidetes was deleterious.<br><br>CONCLUSIONS: Our results suggest clades that may be beneficial to transmit/eliminate through FMT, and provide criteria that may help identify personalized FMT donors to more effectively maintain remission in CD patients. The framework established here creates a foundation for future studies centered around the application of FMT and defined microbial communities as a therapeutic approach for treating CD.}, }
@article {pmid32859933, year = {2020}, author = {Ianiro, G and Rossi, E and Thomas, AM and Schinzari, G and Masucci, L and Quaranta, G and Settanni, CR and Lopetuso, LR and Armanini, F and Blanco-Miguez, A and Asnicar, F and Consolandi, C and Iacovelli, R and Sanguinetti, M and Tortora, G and Gasbarrini, A and Segata, N and Cammarota, G}, title = {Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase inhibitors in patients with metastatic renal cell carcinoma.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4333}, pmid = {32859933}, issn = {2041-1723}, mesh = {Aged ; Carcinoma, Renal Cell/*complications ; Diarrhea/*therapy ; Double-Blind Method ; Drug Therapy ; Dysbiosis ; Enzyme Inhibitors/*metabolism ; Fecal Microbiota Transplantation/*methods ; Feces ; Female ; Gastrointestinal Microbiome ; Humans ; Kidney Neoplasms/*complications ; Male ; Middle Aged ; Tissue Donors ; Tyrosine/*metabolism ; }, abstract = {Diarrhoea is one of the most burdensome and common adverse events of chemotherapeutics, and has no standardised therapy to date. Increasing evidence suggests that the gut microbiome can influence the development of chemotherapy-induced diarrhoea. Here we report findings from a randomised clinical trial of faecal microbiota transplantation (FMT) to treat diarrhoea induced by tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (ClinicalTrials.gov number: NCT04040712). The primary outcome is the resolution of diarrhoea four weeks after the end of treatments. Twenty patients are randomised to receive FMT from healthy donors or placebo FMT (vehicle only). Donor FMT is more effective than placebo FMT in treating TKI-induced diarrhoea, and a successful engraftment is observed in subjects receiving donor faeces. No serious adverse events are observed in both treatment arms. The trial meets pre-specified endpoints. Our findings suggest that the therapeutic manipulation of gut microbiota may become a promising treatment option to manage TKI-dependent diarrhoea.}, }
@article {pmid32859898, year = {2020}, author = {Metwaly, A and Dunkel, A and Waldschmitt, N and Raj, ACD and Lagkouvardos, I and Corraliza, AM and Mayorgas, A and Martinez-Medina, M and Reiter, S and Schloter, M and Hofmann, T and Allez, M and Panes, J and Salas, A and Haller, D}, title = {Integrated microbiota and metabolite profiles link Crohn's disease to sulfur metabolism.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4322}, pmid = {32859898}, issn = {2041-1723}, mesh = {Adolescent ; Adult ; Animals ; Bacteria/classification/genetics/metabolism ; Crohn Disease/drug therapy/*metabolism/*microbiology ; Disease Models, Animal ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Hematopoietic Stem Cell Transplantation ; Humans ; Interleukin-10/genetics ; Male ; Metagenome ; Mice ; Mice, Knockout ; RNA, Ribosomal, 16S/genetics ; Remission Induction ; Sulfur/*metabolism ; Young Adult ; }, abstract = {Gut microbial and metabolite alterations have been linked to the pathogenesis of inflammatory bowel diseases. Here we perform a multi-omics microbiome and metabolite analysis of a longitudinal cohort of Crohn's disease patients undergoing autologous hematopoietic stem cell transplantation, and investigational therapy that induces drug free remission in a subset of patients. Via comparison of patients who responded and maintained remission, responded but experienced disease relapse and patients who did not respond to therapy, we identify shared functional signatures that correlate with disease activity despite the variability of gut microbiota profiles at taxonomic level. These signatures reflect the disease state when transferred to gnotobiotic mice. Taken together, the integration of microbiome and metabolite profiles from human cohort and mice improves the predictive modelling of disease outcome, and allows the identification of a network of bacteria-metabolite interactions involving sulfur metabolism as a key mechanism linked to disease activity in Crohn's disease.}, }
@article {pmid32857289, year = {2021}, author = {Wang, Y and Liu, F and Zhang, G and Su, Y and Sun, X and Chen, Q and Wang, C and Fu, H and He, Y and Zhu, X and Liu, X and Lv, M and Zhao, X and Zhao, X and Li, Y and Wang, Q and Huang, X and Zhang, X}, title = {Gut microbiome alterations and its link to corticosteroid resistance in immune thrombocytopenia.}, journal = {Science China. Life sciences}, volume = {64}, number = {5}, pages = {766-783}, pmid = {32857289}, issn = {1869-1889}, mesh = {Adrenal Cortex Hormones/*administration &amp; dosage ; Drug Resistance/*genetics ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Humans ; Metagenomics ; Protein Interaction Maps ; Purpura, Thrombocytopenic, Idiopathic/*drug therapy/*microbiology ; }, abstract = {Quantitative metagenomic studies have linked the gut microbiota to autoimmune disorders. Here, we performed deep shotgun metagenomic sequencing of fecal samples from 99 immune thrombocytopenia (ITP) patients and 52 healthy controls. Dysbiosis in the gut microbiome of ITP was detected phylogenetically and functionally, and classifier based on species markers distinguished individuals with ITP from healthy controls. In particular, the abundance of Ruminococcus gnavus, Bifidobacterium longum and Akkermansia muciniphila was markedly increased in treatment-naïve ITP patients, and the alterations of microbial species were correlated with clinical indices. Functionally, the secondary bile acid biosynthesis and flagellar assembly were depleted in the gut microbiota of ITP, which may contribute to the onset of ITP by affecting the immune system. Furthermore, we found that corticosteroid treatment affected the gut microbiome of ITP. Compared with corticosteroid-sensitive ITP patients, we identified that the corticosteroid-resistant ITP patients displayed a distinct gut microbiome, which was different from that of the treatment-naïve ITP patients. Together, we provided support for the critical role of gut microbiota in the development of ITP and established a foundation for further research characterizing gut microbiota in relation to corticosteroid resistance of ITP.}, }
@article {pmid32856048, year = {2020}, author = {Ahn, IS and Lang, JM and Olson, CA and Diamante, G and Zhang, G and Ying, Z and Byun, HR and Cely, I and Ding, J and Cohn, P and Kurtz, I and Gomez-Pinilla, F and Lusis, AJ and Hsiao, EY and Yang, X}, title = {Host Genetic Background and Gut Microbiota Contribute to Differential Metabolic Responses to Fructose Consumption in Mice.}, journal = {The Journal of nutrition}, volume = {150}, number = {10}, pages = {2716-2728}, pmid = {32856048}, issn = {1541-6100}, support = {F31 MH090749/MH/NIMH NIH HHS/United States ; T32 DK007789/DK/NIDDK NIH HHS/United States ; F31 AG064844/AG/NIA NIH HHS/United States ; T32 ES015457/ES/NIEHS NIH HHS/United States ; P01 HL030568/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*drug effects ; Cecum/microbiology ; Energy Metabolism/*drug effects/*genetics ; Fecal Microbiota Transplantation ; Feces/microbiology ; Fructose/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Male ; Mice ; Mice, Inbred Strains ; Random Allocation ; }, abstract = {BACKGROUND: It is unclear how high fructose consumption induces disparate metabolic responses in genetically diverse mouse strains.<br><br>OBJECTIVE: We aimed to investigate whether the gut microbiota contributes to differential metabolic responses to fructose.<br><br>METHODS: Eight-week-old male C57BL/6J (B6), DBA/2J (DBA), and FVB/NJ (FVB) mice were given 8% fructose solution or regular water (control) for 12 wk. The gut microbiota composition in cecum and feces was analyzed using 16S ribosomal DNA sequencing, and permutational multivariate ANOVA (PERMANOVA) was used to compare community across mouse strains, treatments, and time points. Microbiota abundance was correlated with metabolic phenotypes and host gene expression in hypothalamus, liver, and adipose tissues using Biweight midcorrelation. To test the causal role of the gut microbiota in determining fructose response, we conducted fecal transplants from B6 to DBA mice and vice versa for 4 wk, as well as gavaged antibiotic-treated DBA mice with Akkermansia for 9 wk, accompanied with or without fructose treatment.<br><br>RESULTS: Compared with B6 and FVB, DBA mice had significantly higher Firmicutes to Bacteroidetes ratio and lower baseline abundance of Akkermansia and S24-7 (P <&#xa0;0.05), accompanied by metabolic dysregulation after fructose consumption. Fructose altered specific microbial taxa in individual mouse strains, such as a 7.27-fold increase in Akkermansia in B6 and 0.374-fold change in Rikenellaceae in DBA (false discovery rate <5%), which demonstrated strain-specific correlations with host metabolic and transcriptomic phenotypes. Fecal transplant experiments indicated that B6 microbes conferred resistance to fructose-induced weight gain in DBA mice (F&#xa0;=&#xa0;43.1, P <&#xa0;0.001), and Akkermansia colonization abrogated the fructose-induced weight gain (F&#xa0;=&#xa0;17.8, P&#xa0;<&#xa0;0.001) and glycemic dysfunctions (F&#xa0;=&#xa0;11.8, P&#xa0;=&#xa0;0.004) in DBA mice.<br><br>CONCLUSIONS: Our findings support that differential microbiota composition between mouse strains is partially responsible for host metabolic sensitivity to fructose, and that Akkermansia is a key bacterium that confers resistance to fructose-induced metabolic dysregulation.}, }
@article {pmid32853742, year = {2021}, author = {Zhu, H and He, YS and Ma, J and Zhou, J and Kong, M and Wu, CY and Mao, Q and Lin, G and Li, SL}, title = {The dual roles of ginsenosides in improving the anti-tumor efficiency of cyclophosphamide in mammary carcinoma mice.}, journal = {Journal of ethnopharmacology}, volume = {265}, number = {}, pages = {113271}, doi = {10.1016/j.jep.2020.113271}, pmid = {32853742}, issn = {1872-7573}, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/*pharmacology ; Apoptosis/drug effects ; Cyclophosphamide/administration &amp; dosage/*pharmacology ; Cytokines/blood ; Female ; Gastrointestinal Microbiome/drug effects ; Ginsenosides/administration &amp; dosage/*pharmacology ; Mammary Neoplasms, Experimental/*drug therapy/pathology ; Mice ; Mice, Inbred ICR ; NF-E2-Related Factor 2/metabolism ; NF-kappa B/metabolism ; RNA, Ribosomal, 16S ; Survival Rate ; }, abstract = {Cyclophosphamide (CTX) is a first line chemotherapeutic agent, but often limited for its unstable therapeutic effect and serious side effects. Ginsenosides could facilitate the anti-tumor efficiency of CTX, including benefiting therapeutic effect and decreasing side effects.<br><br>AIM OF THE STUDY: To investigate the potential mechanism of ginsenosides on benefiting the anti-tumor efficiency of CTX.<br><br>MATERIALS AND METHODS: Mammary carcinoma mice were applied to investigate the anti-tumor efficiency and potential mechanism of combinational treatment of ginsenosides and CTX. Therapeutic effect was evaluated based on survival rate, tumor burden, tumor growth inhibition rate, and apoptosis and histological changes of tumor tissues. Anti-tumor immunity was studied by measuring serum level of anti-tumor cytokines. Gut mucositis, one of lethal side effects of CTX, was evaluated by diarrhea degree, gut permeability and tight junction proteins expressions. Gut microbial diversity was analyzed by 16S rRNA gene sequencing, and fecal transplant and antibiotics sterilized animals were performed to evaluate the therapeutic effect of gut microbiota on tumor suppression.<br><br>RESULTS: Ginsenosides facilitated the therapeutic effect of CTX in mice, which manifested as prolonged survival rate, decreased tumor burden, as well as enhanced tumor growth inhibition rate and apoptosis. The favoring effect was related to elevation of anti-tumor immunity which manifested as the increased anti-tumor cytokines (INF-&#x3b3;, IL-17, IL-2 and IL-6). Further studies indicated the elevation was ascribed to ginsenosides promoted reproduction of gut probiotics including Akkermansia, Bifidobacterium and Lactobacillus. Moreover, co-administration of ginsenosides in mice alleviated CTX-induced gut mucositis, including lower gut permeability, less diarrhea, less epithelium damage and higher tight junction proteins. Further researches suggested the alleviation was related to ginsenosides activated Nrf2 and inhibited NF&#x3ba;B pathways.<br><br>CONCLUSION: Ginsenosides show dual roles to facilitate the anti-tumor efficiency of CTX, namely promote the anti-tumor immunity through maintaining gut microflora and ameliorate gut mucositis by modulating Nrf2 and NF&#x3ba;B pathways.}, }
@article {pmid32852834, year = {2020}, author = {Ianiro, G and Porcari, S and Ford, AC and Gasbarrini, A and Cammarota, G}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-room for improvement.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {5}, pages = {923-924}, doi = {10.1111/apt.15923}, pmid = {32852834}, issn = {1365-2036}, mesh = {Colonoscopy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid32852821, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-room for improvement. Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {5}, pages = {925-926}, doi = {10.1111/apt.15942}, pmid = {32852821}, issn = {1365-2036}, mesh = {Colonoscopy ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid32850913, year = {2020}, author = {Ouyang, J and Isnard, S and Lin, J and Fombuena, B and Peng, X and Nair Parvathy, S and Chen, Y and Silverman, MS and Routy, JP}, title = {Treating From the Inside Out: Relevance of Fecal Microbiota Transplantation to Counteract Gut Damage in GVHD and HIV Infection.}, journal = {Frontiers in medicine}, volume = {7}, number = {}, pages = {421}, pmid = {32850913}, issn = {2296-858X}, abstract = {The gastrointestinal (GI) tract is a complex and well-balanced milieu of anatomic and immunological barriers. The epithelial surface of the GI tract is colonized by trillions of microorganisms, known as the gut microbiota, which is considered an "organ" with distinctive endocrine and immunoregulatory functions. Dysregulation of the gut microbiota composition, termed dysbiosis, has been associated with epithelial damage and translocation of microbial products into the circulating blood. Dysbiosis, increased gut permeability and chronic inflammation play a major role on the clinical outcome of inflammatory bowel diseases, graft-vs.-host disease (GVHD) and HIV infection. In this review, we focus on GVHD and HIV infection, conditions sharing gut immune damage leading to dysbiosis. The degree of dysbiosis and level of epithelial gut damage predict poor clinical outcome in both conditions. Emerging interventions are therefore warranted to promote gut microbiota homeostasis and improve intestinal barrier function. Interventions such as anti-inflammatory medications, and probiotics have toxicity and/or limited transitory effects, justifying innovative approaches. Fecal microbiota transplantation (FMT) is one such approach where fecal microorganisms are transferred from healthy donors into the GI tract of the recipient to restore microbiota composition in patients with Clostridium difficile-induced colitis or inflammatory bowel diseases. Preliminary findings point toward a beneficial effect of FMT to improve GVHD and HIV-related outcomes through the engraftment of beneficial donor bacteria, notably those producing anti-inflammatory metabolites. Herein, we critically review the potential for FMT in alleviating dysbiosis and gut damage in patients with GVHD or HIV-infection. Understanding the underlying mechanism by which FMT restores gut function will pave the way toward novel scalable and targeted interventions.}, }
@article {pmid32850467, year = {2020}, author = {Sehgal, R and Bedi, O and Trehanpati, N}, title = {Role of Microbiota in Pathogenesis and Management of Viral Hepatitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {341}, pmid = {32850467}, issn = {2235-2988}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Hepatitis, Viral, Human/therapy ; Humans ; Liver Cirrhosis/therapy ; *Microbiota ; }, abstract = {Hepatitis is a condition that can be self-limiting or can progress to fibrosis (scarring), cirrhosis, or liver cancer. These days, gut microbiota becomes an important part of our immune system, which is important for disease progression or recovery. Translocation of gut microbial and metabolic products causes intestinal inflammation by modulating immune cells leading to impairment of the primary barrier. But there are limited studies discussing pathogenesis and management of hepatitis with gut microbiota. In this review, we have discussed the role of gut microbiota in pathogenesis and management of various hepatitis, especially hepatitis B and C. We have discussed the role of bacterial products, LPS-TLR4 pathway, and unmethylated CpG DNA, which ultimately affects downstream NF-kB signaling in hepatitis. Finally, we have discussed the role of fecal microbiota transplantation in the management of hepatitis.}, }
@article {pmid32849912, year = {2020}, author = {Barberio, B and Massimi, D and Bonfante, L and Facchin, S and Calò, L and Trevenzoli, M and Savarino, EV and Cattelan, AM}, title = {Fecal microbiota transplantation for norovirus infection: a clinical and microbiological success.}, journal = {Therapeutic advances in gastroenterology}, volume = {13}, number = {}, pages = {1756284820934589}, pmid = {32849912}, issn = {1756-283X}, }
@article {pmid32849279, year = {2020}, author = {Sfera, A and Osorio, C and Diaz, EL and Maguire, G and Cummings, M}, title = {The Other Obesity Epidemic-Of Drugs and Bugs.}, journal = {Frontiers in endocrinology}, volume = {11}, number = {}, pages = {488}, pmid = {32849279}, issn = {1664-2392}, mesh = {Animals ; Dysbiosis/*complications ; *Gastrointestinal Microbiome ; Humans ; Obesity/chemically induced/*epidemiology/microbiology ; Pharmaceutical Preparations/*administration &amp; dosage ; Psychotropic Drugs/*adverse effects ; }, abstract = {Chronic psychiatric patients with schizophrenia and related disorders are frequently treatment-resistant and may require higher doses of psychotropic drugs to remain stable. Prolonged exposure to these agents increases the risk of weight gain and cardiometabolic disorders, leading to poorer outcomes and higher medical cost. It is well-established that obesity has reached epidemic proportions throughout the world, however it is less known that its rates are two to three times higher in mentally ill patients compared to the general population. Psychotropic drugs have emerged as a major cause of weight gain, pointing to an urgent need for novel interventions to attenuate this unintended consequence. Recently, the gut microbial community has been linked to psychotropic drugs-induced obesity as these agents were found to possess antimicrobial properties and trigger intestinal dysbiosis, depleting Bacteroidetes phylum. Since germ-free animals exposed to psychotropics have not demonstrated weight gain, altered commensal flora composition is believed to be necessary and sufficient to induce dysmetabolism. Conversely, not only do psychotropics disrupt the composition of gut microbiota but the later alter the metabolism of the former. Here we review the role of gut bacterial community in psychotropic drugs metabolism and dysbiosis. We discuss potential biomarkers reflecting the status of Bacteroidetes phylum and take a closer look at nutritional interventions, fecal microbiota transplantation, and transcranial magnetic stimulation, strategies that may lower obesity rates in chronic psychiatric patients.}, }
@article {pmid32846251, year = {2021}, author = {Li, L and Wang, Q and Gao, Y and Liu, L and Duan, Y and Mao, D and Luo, Y}, title = {Colistin and amoxicillin combinatorial exposure alters the human intestinal microbiota and antibiotic resistome in the simulated human intestinal microbiota.}, journal = {The Science of the total environment}, volume = {750}, number = {}, pages = {141415}, doi = {10.1016/j.scitotenv.2020.141415}, pmid = {32846251}, issn = {1879-1026}, mesh = {Amoxicillin ; Anti-Bacterial Agents ; *Colistin ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Antibiotics treatment could cause the dysbiosis of human intestinal microbiota and antibiotic resistome. Fecal microbiota transplantation (FMT) has been an efficacious treatment to restore the dysbiosis of intestinal microbiota in a variety of intestinal diseases. However, to data, the effect of the combinatorial antibiotic treatment on microbiota, antibiotic resistome and the FMT for restoration affected by combinatorial antibiotic exposure in the human intestinal microbiota remain unclear. In this study, we systematically investigated the effect of the colistin and amoxicillin combinatorial exposure in the simulator of the human intestinal microbial ecosystem (SHIME) and found that this combinatorial exposure significantly altered (p < 0.05) the human intestinal microbiota and antibiotic resistome. The shift of bacterial community and antibiotic resistome could incompletely recovery to baseline by FMT treatment after combinatorial antibiotic exposure. Additionally, the variance of antibiotic resistome was dominantly driven by the bacterial community (41.18%-68.03%) after the combinatorial antibiotic exposure. Overall, this study first to investigate the influence of the colistin and amoxicillin combinatorial exposure on the intestinal microbiota and antibiotic resistome, and assess the FMT recovery in the simulated human intestinal microbiota, which may potentially provide a correct administration of antibiotics and application of FMT in the clinic.}, }
@article {pmid32844470, year = {2020}, author = {Uzawa, H and Kohno, D and Koga, T and Sasaki, T and Fukunaka, A and Okuno, T and Jo-Watanabe, A and Kazuno, S and Miyatsuka, T and Kitamura, T and Fujitani, Y and Watada, H and Saeki, K and Yokomizo, T}, title = {Leukotriene A4 hydrolase deficiency protects mice from diet-induced obesity by increasing energy expenditure through neuroendocrine axis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {34}, number = {10}, pages = {13949-13958}, doi = {10.1096/fj.202001148R}, pmid = {32844470}, issn = {1530-6860}, mesh = {Adipose Tissue, Brown/metabolism ; Animals ; Catecholamines/metabolism ; Cells, Cultured ; Diet, High-Fat/adverse effects ; *Energy Metabolism ; Epoxide Hydrolases/deficiency/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/etiology/*genetics/metabolism ; Phenotype ; Receptors, Leukotriene B4/genetics/metabolism ; Thermogenesis ; Thyroid Hormones/*blood ; Thyrotropin/*blood ; }, abstract = {Obesity is a health problem worldwide, and brown adipose tissue (BAT) is important for energy expenditure. Here, we explored the role of leukotriene A4 hydrolase (LTA4 H), a key enzyme in the synthesis of the lipid mediator leukotriene B4 (LTB4), in diet-induced obesity. LTA4 H-deficient (LTA4 H-KO) mice fed a high-fat diet (HFD) showed a lean phenotype, and bone-marrow transplantation studies revealed that LTA4 H-deficiency in non-hematopoietic cells was responsible for this lean phenotype. LTA4 H-KO mice exhibited greater energy expenditure, but similar food intake and fecal energy loss. LTA4 H-KO BAT showed higher expression of thermogenesis-related genes. In addition, the plasma thyroid-stimulating hormone and thyroid hormone concentrations, as well as HFD-induced catecholamine secretion, were higher in LTA4 H-KO mice. In contrast, LTB4 receptor (BLT1)-deficient mice did not show a lean phenotype, implying that the phenotype of LTA4 H-KO mice is independent of the LTB4 /BLT1 axis. These results indicate that LTA4 H mediates the diet-induced obesity by reducing catecholamine and thyroid hormone secretion.}, }
@article {pmid32843743, year = {2021}, author = {Khoruts, A and Staley, C and Sadowsky, MJ}, title = {Faecal microbiota transplantation for Clostridioides difficile: mechanisms and pharmacology.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {18}, number = {1}, pages = {67-80}, pmid = {32843743}, issn = {1759-5053}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; *Clostridioides difficile/metabolism/pathogenicity/physiology ; Clostridium Infections/etiology/*physiopathology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent Clostridioides difficile infection that cannot be cured with antibiotics alone. Understanding the complex biology and pathogenesis of C. difficile infection, which we discuss in this Perspective, is essential for understanding the potential mechanisms by which FMT cures this disease. Although FMT has already entered clinical practice, different microbiota-based products are currently in clinical trials and are vying for regulatory approval. However, all these therapeutics belong to an entirely new class of agents that require the development of a new branch of pharmacology. Characterization of microbiota therapeutics uses novel and rapidly evolving technologies and requires incorporation of microbial ecology concepts. Here, we consider FMT within a pharmacological framework, including its essential elements: formulation, pharmacokinetics and pharmacodynamics. From this viewpoint, multiple gaps in knowledge become apparent, identifying areas that require systematic research. This knowledge is needed to help clinical providers use microbiota therapeutics appropriately and to facilitate development of next-generation microbiota products with improved safety and efficacy. The discussion here is limited to FMT as a representative of microbiota therapeutics and recurrent C. difficile as the indication; however, consideration of the intrinsic basic principles is relevant to this entire class of microbiota-based therapeutics.}, }
@article {pmid32843418, year = {2020}, author = {Costello, SP and Day, A and Yao, CK and Bryant, RV}, title = {Faecal microbiota transplantation (FMT) with dietary therapy for acute severe ulcerative colitis.}, journal = {BMJ case reports}, volume = {13}, number = {8}, pages = {}, pmid = {32843418}, issn = {1757-790X}, mesh = {Adult ; Colitis, Ulcerative/*therapy ; Colon, Sigmoid/diagnostic imaging/pathology ; *Diet, Protein-Restricted ; *Fecal Microbiota Transplantation ; Humans ; Male ; Treatment Outcome ; Young Adult ; }, abstract = {A 19-year-old man presented with acute severe ulcerative colitis. He was taking azathioprine (therapeutic metabolites) and sulphasalazine as well as infliximab with a therapeutic drug level. On day 3 of hydrocortisone therapy, he met day Oxford criteria with >8 bloody stools per day and was given faecal microbiota transplantation and subsequently commenced on dietary therapy combining several strategies-(1) increased intake of fermentable fibres, (2) reduced intake of overall and sulfur-containing protein and (3) restriction of sulfate and sulfite food additives. At week 8 assessment, he was in clinical and endoscopic remission and remained in clinical and endoscopic remission at 12 months.}, }
@article {pmid32843357, year = {2021}, author = {Sun, D and Bai, R and Zhou, W and Yao, Z and Liu, Y and Tang, S and Ge, X and Luo, L and Luo, C and Hu, GF and Sheng, J and Xu, Z}, title = {Angiogenin maintains gut microbe homeostasis by balancing α-Proteobacteria and Lachnospiraceae.}, journal = {Gut}, volume = {70}, number = {4}, pages = {666-676}, pmid = {32843357}, issn = {1468-3288}, support = {R01 HL135160/HL/NHLBI NIH HHS/United States ; }, mesh = {Alphaproteobacteria/*drug effects ; Animals ; Clostridiales/*drug effects ; Colitis/*drug therapy ; Dysbiosis/*drug therapy ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Homeostasis ; Mice ; Ribonuclease, Pancreatic/administration &amp; dosage/*pharmacology ; }, abstract = {OBJECTIVE: Antimicrobial peptides (AMPs) play essential roles in maintaining gut health and are associated with IBD. This study is to elucidate the effect of angiogenin (ANG), an intestine-secreted AMP, on gut microbiota and its relevance with IBD.<br><br>DESIGN: The effect of ANG on microbiota and its contribution to colitis were evaluated in different colitis models with co-housing and faecal microbiota transplantation. ANG-regulated bacteria were determined by 16S rDNA sequencing and their functions in colitis were analysed by bacterial colonisation. The species-specific antimicrobial activity of ANG and its underlying mechanism were further investigated with microbiological and biochemical methods. ANG level and the key bacteria were characterised in IBD faecal samples.<br><br>RESULTS: ANG regulated microbiota composition and inhibited intestinal inflammation. Specifically, Ang1 deficiency in mice led to a decrease in the protective gut commensal strains of Lachnospiraceae but an increase in the colitogenic strains of &#x3b1;-Proteobacteria. Direct binding of ANG to &#x3b1;-Proteobacteria resulted in lethal disruption of bacterial membrane integrity, and consequently promoted the growth of Lachnospiraceae, which otherwise was antagonised by &#x3b1;-Proteobacteria. Oral administration of ANG1 reversed the dysbiosis and attenuated the severity of colitis in Ang1-deficient mice. The correlation among ANG, the identified bacteria and IBD status was established in patients.<br><br>CONCLUSION: These findings demonstrate a novel role of ANG in shaping gut microbe composition and thus maintaining gut health, suggesting that the ANG-microbiota axis could be developed as a potential preventive and/or therapeutic approach for dysbiosis-related gut diseases.}, }
@article {pmid32842435, year = {2020}, author = {Zhang, W and Jiang, KW}, title = {[Role of gut microbiota in carcinogenesis and treatment for colorectal cancer].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {5}, pages = {516-520}, doi = {10.3760/cma.j.cn.441530-20190820-00314}, pmid = {32842435}, issn = {1671-0274}, support = {2016YFC0106000//National Key Research and Development Plan/ ; }, mesh = {*Carcinogenesis/genetics/immunology/metabolism/pathology ; Colorectal Neoplasms/*microbiology/pathology/physiopathology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/*microbiology/pathology/physiopathology ; Probiotics/therapeutic use ; Tumor Microenvironment/physiology ; }, abstract = {Colorectal cancer is one of the most common malignant tumors of digestive tract. There are a large number of microorganisms in the digestive tract. Under normal physiological conditions, intestinal microorganisms can help with digestion and absorption, resist pathogen invasion and regulate the proliferation of intestinal mucosal cells. However, intestinal microflora imbalance will affect the intestinal microenvironment and intestinal cell function, and is closely related to the incidence and progression of colorectal cancer. Firstly, this paper introduces the changes of intestinal flora in patients with colorectal cancer, and then summarizes the mode of intestinal flora participating in the occurrence of colorectal cancer from the macro level. Then, we elaborate the involvement of intestinal flora in colorectal cancer from the aspects of cytokine-dependent chronic inflammation, DNA damage of intestinal epithelial cells, carcinogenic metabolites of intestinal flora and cellular enzymes, and changes of intestinal immune system. The pathogenesis of colorectal cancer provides a reference for further study of the pathogenesis of colorectal cancer. Finally, from the perspective of intestinal flora and colorectal cancer treatment, we analyze the significance of probiotics and bacterial flora transplantation for the treatment of colorectal cancer, and provide some new treatment ideas and methods that may be useful for the treatment of colorectal cancer.}, }
@article {pmid32842434, year = {2020}, author = {Zhang, XY and Chen, QY and Li, N and Qin, HL}, title = {[Indication selection and clinical application strategies of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {5}, pages = {509-515}, doi = {10.3760/cma.j.cn.441530-20200110-00015}, pmid = {32842434}, issn = {1671-0274}, support = {SHDC12017112, SHDC12019114//Emerging Cutting-Edge Technology Joint Research Projects of Shanghai/ ; }, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; Donor Selection ; Fecal Microbiota Transplantation/adverse effects/*methods/standards ; Feces/microbiology ; Humans ; Treatment Outcome ; }, abstract = {Fecal microbiota transplant (FMT) has become an effective method for the treatment of recurrent C. difficile infection. In addition, it has shown certain effects in other diseases inside and outside the intestine. A large number of clinical trials have been carried out. However, there is still lack of uniform standard for strategies of FMT. In this paper, we discussed the current hot and controversial issues of FMT from the aspects of indication, donor screening, fecal suspension quality control, methodology, follow-up and efficacy judgment, treatment of adverse reaction and ethical supervision based on our team's clinical experience.}, }
@article {pmid32841976, year = {2020}, author = {Collins, M and DeWitt, M}, title = {Fecal microbiota transplantation in the treatment of Crohn disease.}, journal = {JAAPA : official journal of the American Academy of Physician Assistants}, volume = {33}, number = {9}, pages = {34-37}, doi = {10.1097/01.JAA.0000694964.31958.b9}, pmid = {32841976}, issn = {1547-1896}, mesh = {Costs and Cost Analysis ; Crohn Disease/etiology/microbiology/*therapy ; Dysbiosis/etiology ; *Fecal Microbiota Transplantation/economics/methods/trends ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mesalamine/adverse effects ; Safety ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is an alternative treatment option with minimal risk for patients with Crohn disease. This article explains FMT and how it effectively targets the gut microbiota changes associated with the pathogenesis of Crohn disease.}, }
@article {pmid32841646, year = {2020}, author = {Kelly, CR and Laine, LA and Wu, GD}, title = {Monitoring Fecal Microbiota Transplantation Practice in a Rapidly Evolving Health and Regulatory Environment.}, journal = {Gastroenterology}, volume = {159}, number = {6}, pages = {2004-2006}, pmid = {32841646}, issn = {1528-0012}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {COVID-19/prevention &amp; control/transmission ; Clostridium Infections/microbiology/*therapy ; Donor Selection/standards ; Escherichia coli/pathogenicity ; Escherichia coli Infections/prevention &amp; control/transmission ; Fecal Microbiota Transplantation/adverse effects/*standards ; Feces/*microbiology ; Humans ; *Practice Guidelines as Topic ; Registries/standards/statistics &amp; numerical data ; Therapies, Investigational/adverse effects/*standards ; United States ; United States Food and Drug Administration/standards ; }, }
@article {pmid32840125, year = {2020}, author = {Oduro-Donkor, D and Turner, MC and Farnaud, S and Renshaw, D and Kyrou, I and Hanson, P and Hattersley, J and Weickert, MO and Menon, V and Randeva, HS and Barber, TM}, title = {Modification of fecal microbiota as a mediator of effective weight loss and metabolic benefits following bariatric surgery.}, journal = {Expert review of endocrinology &amp; metabolism}, volume = {15}, number = {5}, pages = {363-373}, doi = {10.1080/17446651.2020.1801412}, pmid = {32840125}, issn = {1744-8417}, mesh = {Bariatric Surgery/methods ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Obesity/microbiology/*therapy ; *Weight Loss ; }, abstract = {INTRODUCTION: Bariatric surgery (primarily Laparoscopic Sleeve Gastrectomy [LSG] and Roux-en-Y Gastric Bypass [RYGB]) is an efficacious and durable therapeutic option for weight loss in obesity. The mechanisms that mediate weight loss following bariatric surgery remain incompletely understood.<br><br>AREAS COVERED: Pubmed search of published data on fecal microbiota, metabolic health, LSG, and RYGB. The fecal microbiome plays a key role in the establishment and maintenance of metabolic wellbeing, and may also contribute (through fecal dysbiosis) to metabolic dysfunction. LSG and RYGB both result in characteristic, procedure-specific changes to the fecal microbiota that may mediate at least some of the resultant weight-loss and metabolically beneficial effects, when applied to the management of obesity.<br><br>EXPERT OPINION: The human fecal microbiome, containing around 100 trillion microbes, evolved over millions of years and interacts symbiotically with its human host. Rodent-based studies have provided insights into the complexities of the gut-microbiome-brain axis. This includes the important role of the gut microbiome in the mediation of normal immunological development, inflammatory pathways, metabolic functioning, hypothalamic appetite regulation, and the absorption of essential nutrients as by-products of bacterial metabolism. Fecal transformation is likely to provide an important therapeutic target for future prevention and management of obesity and metabolic dysfunction.}, }
@article {pmid32839368, year = {2020}, author = {Song, DS}, title = {[Medical Treatment of Alcoholic Liver Disease].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {76}, number = {2}, pages = {65-70}, doi = {10.4166/kjg.2020.76.2.65}, pmid = {32839368}, issn = {2233-6869}, mesh = {Acetylcysteine/therapeutic use ; Adrenal Cortex Hormones/therapeutic use ; Enteral Nutrition ; Fecal Microbiota Transplantation ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Humans ; Liver Diseases, Alcoholic/drug therapy/pathology/*therapy ; Pentoxifylline/therapeutic use ; Severity of Illness Index ; }, abstract = {Alcoholic liver disease is a major cause of liver disease that results in significant morbidity and mortality in Korea. Abstinence is the most important strategy to prevent disease progression. Corticosteroids improve the one-month survival in patients with severe alcoholic hepatitis, but it was not effective on long-term survival. An N-acetylcysteine treatment combined with corticosteroids may provide a short-term survival benefit than corticosteroids alone. Pentoxifylline is unlikely to affect short-term survival. Hence, studies on new therapies, such as granulocyte colony-stimulating factor and fecal microbiota transplantation, are ongoing. This paper briefly reviews the current knowledge of the medical treatment of alcoholic liver disease.}, }
@article {pmid32839363, year = {2021}, author = {Yoon, H and Shim, HI and Seol, M and Shin, CM and Park, YS and Kim, N and Lee, DH}, title = {Factors Related to Outcomes of Fecal Microbiota Transplantation in Patients with Clostridioides difficile Infection.}, journal = {Gut and liver}, volume = {15}, number = {1}, pages = {61-69}, pmid = {32839363}, issn = {2005-1212}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; RNA, Ribosomal, 16S/genetics ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND/AIMS: The aim of this study was to evaluate factors related to outcomes of fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) and viability of frozen stock for FMT.<br><br>METHODS: Clinical data of patients who had received FMT for CDI were prospectively collected. Next-generation 16S rRNA gene sequencing of bacteria was performed from donors' and recipients' stool. Colony-forming units (CFUs) of cultures from frozen stock solutions for FMT were measured at 0, 4, 8, 12, 24, 48 weeks after preparation of the solutions.<br><br>RESULTS: In total, 25 FMT procedures were performed in 20 cases (14 fresh and 11 frozen FMT). Forty-five percent of cases involved fulminant CDI. The overall success rate was 55% after the 1st FMT and 75% after the 2nd FMT. The success rate was significantly higher in partially treated CDI than in refractory CDI (100% vs 71.4%; p=0.001). In successful cases only, the decrease in alpha-diversity in the recipient stool microbiomes was recovered after FMT to a level similar to that in donor stools. There was a significant difference in the microbiome composition in pre-FMT recipients' stool between successful and failed cases (p=0.001). The CFUs of frozen solution for FMT did not decrease for 48 weeks in both aerobic and anaerobic cultures.<br><br>CONCLUSIONS: FMT is highly effective in partially treated CDI but not in refractory CDI. The microbiome differs between failed and successful cases. Frozen stock for FMT is viable up to 48 weeks.}, }
@article {pmid32835916, year = {2020}, author = {Zhan, J and Ma, X and Liu, D and Liang, Y and Li, P and Cui, J and Zhou, Z and Wang, P}, title = {Gut microbiome alterations induced by tributyltin exposure are associated with increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {266}, number = {Pt 3}, pages = {115276}, doi = {10.1016/j.envpol.2020.115276}, pmid = {32835916}, issn = {1873-6424}, mesh = {Animals ; Body Weight ; *Gastrointestinal Microbiome ; Glucose ; Homeostasis ; Insulin ; Mice ; Mice, Inbred ICR ; Trialkyltin Compounds ; }, abstract = {Tributyltin (TBT), an organotin compound once widely used in agriculture and industry, has been reported to induce obesity and endocrine disruption. Gut microbiota has a strong connection with the host's physiology. Nevertheless, the influences of TBT exposure on gut microbiota and whether TBT-influenced gut microbiota is related to TBT-induced toxicity remain unclear. To fill these gaps, ICR (CD-1) mice were respectively exposed to TBT at NOEL (L-TBT) and tenfold NOEL (H-TBT) daily by gavage for 8 weeks in the current study. The results showed that TBT exposure significantly increased body weight as well as epididymal fat, and led to adipocyte hypertrophy, dyslipidemia and impaired glucose and insulin homeostasis in mice. Additionally, TBT exposure significantly decreased the levels of T4, T3 and testosterone in serum. Also of note, TBT exposure changed gut microbiota composition mainly by decreasing Bacteroidetes and increasing Firmicutes proportions. To confirm the role of gut microbiota in TBT-induced overweight and hormonal disorders, fecal microbiota transplantation was performed and the mice receiving gut microbiota from H-TBT mice had similar phenotypes with their donor mice including significant body weight and epididymal fat gain, glucose and insulin dysbiosis and hormonal disorders. These results suggested that gut microbiome altered by TBT exposure was involved in the TBT-induced increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice, providing significant evidence and a novel perspective for better understanding the mechanism by which TBT induces toxicity.}, }
@article {pmid32835671, year = {2020}, author = {Badran, M and Khalyfa, A and Ericsson, A and Gozal, D}, title = {Fecal microbiota transplantation from mice exposed to chronic intermittent hypoxia elicits sleep disturbances in naïve mice.}, journal = {Experimental neurology}, volume = {334}, number = {}, pages = {113439}, pmid = {32835671}, issn = {1090-2430}, support = {R56 HL140548/HL/NHLBI NIH HHS/United States ; RF1 AG061824/AG/NIA NIH HHS/United States ; R01 HL130984/HL/NHLBI NIH HHS/United States ; K01 OD019924/OD/NIH HHS/United States ; U42 OD010918/OD/NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation/*adverse effects ; Gastrointestinal Microbiome/*physiology ; Hypoxia/*complications/*physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Sleep Wake Disorders/*etiology/*physiopathology ; }, abstract = {Obstructive sleep apnea (OSA) is a chronic prevalent condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). Evidence suggests that OSA can alter the gut microbiome (GM) diversity and composition that may then promote the occurrence of some of the OSA-associated morbidities. However, it is unclear whether perturbations in the GM caused by IH can elicit sleep disturbances that underlie the increased sleep propensity that occurs in IH-exposed mice. To evaluate this issue, we exposed C57Bl/6 J mice to IH or room air (RA) for 6 weeks, and fecal matter was collected and frozen. C57Bl/6 J naïve mice were then randomly assigned to a fecal microbiota transfer (FMT) protocol for 3 weeks with either IH or RA fecal slur, and their GM was then analyzed using 16 s rRNA sequencing. In addition, FMT recipients underwent sleep recordings using piezoelectric approaches for 3 consecutive days. As anticipated, FMT-IH and FMT-RA mice showed different taxonomic profiles that corresponded to previous effects of IH on GM. Furthermore, FMT-IH mice exhibited increased sleep duration and the frequency of longer sleep bouts during the dark cycle, suggesting increased sleepiness (p < 0.0001 vs. FMT-RA mice). Thus, alterations of GM diversity induced by IH exposures can elicit sleep disturbances in the absence of concurrent IH, suggesting that sleep disturbances can be mediated, at least in part, by IH-induced alterations in GM.}, }
@article {pmid32833508, year = {2020}, author = {Kurian, SM and Gordon, S and Barrick, B and Dadlani, MN and Fanelli, B and Cornell, JB and Head, SR and Marsh, CL and Case, J}, title = {Feasibility and Comparison Study of Fecal Sample Collection Methods in Healthy Volunteers and Solid Organ Transplant Recipients Using 16S rRNA and Metagenomics Approaches.}, journal = {Biopreservation and biobanking}, volume = {18}, number = {5}, pages = {425-440}, doi = {10.1089/bio.2020.0032}, pmid = {32833508}, issn = {1947-5543}, mesh = {Feasibility Studies ; Feces ; Healthy Volunteers ; Humans ; *Metagenomics ; *Organ Transplantation ; Pilot Projects ; Prospective Studies ; RNA, Ribosomal, 16S ; }, abstract = {The human microbiome encompasses a variety of microorganisms that change dynamically and are in close contact with the body. The microbiome influences health and homeostasis, as well as the immune system, and any significant change in this equilibrium (dysbiosis) triggers both acute and chronic health conditions. Microbiome research has surged, in part, due to advanced sequencing technologies enabling rapid, accurate, and cost-effective identification of the microbiome. A major prerequisite for stool sample collection to study the gut microbiome in longitudinal prospective studies requires standardized protocols that can be easily replicated. However, there are still significant bottlenecks to stool specimen collection that contribute to low patient retention rates in microbiome studies. These barriers are further exacerbated in solid organ transplant recipients where diarrhea is estimated to occur in up to half the patient population. We sought to test two relatively easy sample collection methods (fecal swab and wipes) and compare them to the more cumbersome "gold" standard collection method (scoop) using two different sequencing technologies (16S ribosomal RNA sequencing and shotgun metagenomics). Our comparison of the collection methods shows that both the swabs and the wipes are comparable to the scoop method in terms of bacterial abundance and diversity. The swabs, however, were closer in representation to the scoop and were easier to collect and process compared to the wipes. Potential contamination of the swab and the wipe samples by abundant skin commensals was low in our analysis. Comparison of the two sequencing technologies showed that they were complementary, and that 16S sequencing provided enough coverage to detect and differentiate between bacterial species identified in the collected samples. Our pilot study demonstrates that alternative collection methods for stool sampling are a viable option in clinical applications, such as organ transplant studies. The use of these methods may result in better patient retention recruitment rates in serial microbiome studies.}, }
@article {pmid32832499, year = {2020}, author = {Haifer, C and Paramsothy, S and Leong, RW}, title = {Faecal microbiota transplantation as an elixir of youth.}, journal = {Hepatobiliary surgery and nutrition}, volume = {9}, number = {4}, pages = {488-489}, pmid = {32832499}, issn = {2304-3881}, }
@article {pmid32831634, year = {2020}, author = {Li, K and Wei, S and Hu, L and Yin, X and Mai, Y and Jiang, C and Peng, X and Cao, X and Huang, Z and Zhou, H and Ma, G and Liu, Z and Li, H and Zhao, B}, title = {Protection of Fecal Microbiota Transplantation in a Mouse Model of Multiple Sclerosis.}, journal = {Mediators of inflammation}, volume = {2020}, number = {}, pages = {2058272}, pmid = {32831634}, issn = {1466-1861}, mesh = {Animals ; Axons/metabolism ; Blood-Brain Barrier/metabolism ; Blotting, Western ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Fluorescent Antibody Technique ; Gastrointestinal Microbiome/*physiology ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron, Transmission ; Multiple Sclerosis/*microbiology/*therapy ; Myelin Sheath/metabolism ; RNA, Ribosomal, 16S/metabolism ; }, abstract = {Given the growing evidence of a link between gut microbiota (GM) dysbiosis and multiple sclerosis (MS), fecal microbiota transplantation (FMT), aimed at rebuilding GM, has been proposed as a new therapeutic approach to MS treatment. To evaluate the viability of FMT for MS treatment and its impact on MS pathology, we tested FMT in mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We provide evidence that FMT can rectify altered GM to some extent with a therapeutic effect on EAE. We also found that FMT led to reduced activation of microglia and astrocytes and conferred protection on the blood-brain barrier (BBB), myelin, and axons in EAE. Taken together, our data suggest that FMT, as a GM-based therapy, has the potential to be an effective treatment for MS.}, }
@article {pmid32830227, year = {2021}, author = {Zou, J and Zhao, X and Shi, Z and Zhang, Z and Vijay-Kumar, M and Chassaing, B and Gewirtz, AT}, title = {Critical Role of Innate Immunity to Flagellin in the Absence of Adaptive Immunity.}, journal = {The Journal of infectious diseases}, volume = {223}, number = {8}, pages = {1478-1487}, pmid = {32830227}, issn = {1537-6613}, support = {R01 DK083890/DK/NIDDK NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Animals ; *Colitis ; Dysbiosis ; Flagellin/*immunology ; *Homeodomain Proteins/genetics ; *Immunity, Innate ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *NLR Proteins/genetics ; *Toll-Like Receptor 5/genetics ; }, abstract = {BACKGROUND: Bacterial flagellin is a major target of innate and adaptive immunity, both of which can promote and/or compensate for deficiencies in each other's function.<br><br>METHODS: To investigate the role of innate immune detection of flagellin irrespective of adaptive immunity, we examined the consequences of loss of Toll-like receptor 5 (T5) and/or Nod-like receptor 4 (N4) upon a Rag1-deficient background.<br><br>RESULTS: Mice lacking Toll-like receptor 5 and Rag1 (T5/Rag-DKO) exhibited frequent lethal Pasteurellaceae-containing abscesses that prevented breeding of these mice. Mice lacking Toll-like receptor 5, Nod-like receptor 4, and Rag1 (T5/N4/Rag-TKO) also resulted in sporadic lethal abdominal abscesses caused by similar Pasteurellaceae. In the absence of such infections, relative to Rag1-KO, T5/N4/Rag-TKO mice exhibited microbiota encroachment, low-grade inflammation, microbiota dysbiosis, and, moreover were highly prone to Citrobacter infection and developed severe colitis when adoptively transferred with colitogenic T cells. Relative proneness of T5/N4/Rag-TKO mice to T-cell colitis was ablated by antibiotics while fecal microbiota transplant from T5/N4/Rag-TKO mice to wild-type mice transferred proneness to Citrobacter infection, indicating that dysbiosis in T5/N4/Rag-TKO mice contributed to these phenotypes.<br><br>CONCLUSIONS: These results demonstrate a critical role for innate immune detection of flagellin, especially in the intestinal tract and particularly in hosts deficient in adaptive immunity.}, }
@article {pmid32828819, year = {2020}, author = {Banerjee, A and Herring, CA and Chen, B and Kim, H and Simmons, AJ and Southard-Smith, AN and Allaman, MM and White, JR and Macedonia, MC and Mckinley, ET and Ramirez-Solano, MA and Scoville, EA and Liu, Q and Wilson, KT and Coffey, RJ and Washington, MK and Goettel, JA and Lau, KS}, title = {Succinate Produced by Intestinal Microbes Promotes Specification of Tuft Cells to Suppress Ileal Inflammation.}, journal = {Gastroenterology}, volume = {159}, number = {6}, pages = {2101-2115.e5}, pmid = {32828819}, issn = {1528-0012}, support = {T32 LM012412/LM/NLM NIH HHS/United States ; P01 CA028842/CA/NCI NIH HHS/United States ; R01 DK128200/DK/NIDDK NIH HHS/United States ; K01 DK106311/DK/NIDDK NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; P01 CA116087/CA/NCI NIH HHS/United States ; I01 BX001453/BX/BLRD VA/United States ; I01 CX002171/CX/CSRD VA/United States ; P50 CA236733/CA/NCI NIH HHS/United States ; F31 GM120940/GM/NIGMS NIH HHS/United States ; R01 DK103831/DK/NIDDK NIH HHS/United States ; T32 HD007502/HD/NICHD NIH HHS/United States ; KL2 TR002245/TR/NCATS NIH HHS/United States ; R35 CA197570/CA/NCI NIH HHS/United States ; R21 AI142042/AI/NIAID NIH HHS/United States ; T32 AI138932/AI/NIAID NIH HHS/United States ; UM1 CA183727/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Chemoreceptor Cells/*immunology/pathology ; Crohn Disease/*immunology/microbiology/pathology ; DNA, Bacterial/genetics ; Disease Models, Animal ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; Humans ; Ileitis/*immunology/microbiology/pathology ; Ileum/cytology/immunology/microbiology/pathology ; Intestinal Mucosa/cytology/*immunology/microbiology/pathology ; Male ; Mice ; Mice, Knockout ; Protective Factors ; RNA, Ribosomal, 16S/genetics ; RNA-Seq ; Single-Cell Analysis ; Succinic Acid/immunology/metabolism ; }, abstract = {BACKGROUND &amp; AIMS: Countries endemic for parasitic infestations have a lower incidence of Crohn's disease (CD) than nonendemic countries, and there have been anecdotal reports of the beneficial effects of helminths in CD patients. Tuft cells in the small intestine sense and direct the immune response against eukaryotic parasites. We investigated the activities of tuft cells in patients with CD and mouse models of intestinal inflammation.<br><br>METHODS: We used microscopy to quantify tuft cells in intestinal specimens from patients with ileal CD (n&#xa0;= 19), healthy individuals (n&#xa0;= 14), and TNF[&#x394;ARE][/+] mice, which develop Crohn's-like ileitis. We performed single-cell RNA sequencing, mass spectrometry, and microbiome profiling of intestinal tissues from wild-type and Atoh1-knockout mice, which have expansion of tuft cells, to study interactions between microbes and tuft cell populations. We assessed microbe dependence of tuft cell populations using microbiome depletion, organoids, and microbe transplant experiments. We used multiplex imaging and cytokine assays to assess alterations in inflammatory response following expansion of tuft cells with succinate administration in TNF[&#x394;ARE/+] and anti-CD3E CD mouse models.<br><br>RESULTS: Inflamed ileal tissues from patients and mice had reduced numbers of tuft cells, compared with healthy individuals or wild-type mice. Expansion of tuft cells was associated with increased expression of genes that regulate the tricarboxylic acid cycle, which resulted from microbe production of the metabolite succinate. Experiments in which we manipulated the intestinal microbiota of mice revealed the existence of an ATOH1-independent population of tuft cells that was sensitive to metabolites produced by microbes. Administration of succinate to mice expanded tuft cells and reduced intestinal inflammation in TNF[&#x394;ARE/+] mice and anti-CD3E-treated mice, increased GATA3[+] cells and type 2 cytokines (IL22, IL25, IL13), and decreased RORGT[+] cells and type&#xa0;17&#xa0;cytokines (IL23) in a tuft cell-dependent manner.<br><br>CONCLUSIONS: We found that tuft cell expansion reduced chronic intestinal inflammation in mice. Strategies to expand tuft cells might be developed for treatment of CD.}, }
@article {pmid32827625, year = {2020}, author = {Yu, JM and Wang, ZH and Liu, N and Zhang, Q and Dong, YJ and Duan, ZJ}, title = {Complete genome of a novel recombinant human astrovirus and its quasispecies in patients following hematopoietic stem cell transplantation.}, journal = {Virus research}, volume = {288}, number = {}, pages = {198138}, doi = {10.1016/j.virusres.2020.198138}, pmid = {32827625}, issn = {1872-7492}, mesh = {Astroviridae Infections/*virology ; Disease Reservoirs/virology ; Feces/virology ; Genetic Variation ; *Genome, Viral ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunocompromised Host ; Mamastrovirus/classification/*genetics/*isolation &amp; purification ; Phylogeny ; Quasispecies/*genetics ; }, abstract = {Human astroviruses (HAstVs) were first identified in 1975 and can be classified into three clades: classic HAstVs (HAstV 1-8), MLB (MLB1-3) and VA (VA1-5), with MLB and VA were newly identified. Recombination and a high mutation rate make HAstV as one of the rapidly evolving infectious agents. This study reported a novel identified recombinant human astrovirus (Y/1-CHN) and its long existence in two immunocompromised patients with diarrhea following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The identified Yu/1-CHN genome contains 6801 base pairs encoding three open reading frames, with ORF1a best hit to the HAstV1 (Pune strain, 97 % nucleotide identity), while ORF1b and ORF2 best hit to HAstV-5 (DL30 strain, 99 % nucleotide identity). Possible recombination breakpoint was predicted to be located in the boundary of ORF1a and ORF1b. Different quasispecies were found in the host, and the dN/dS ratios of the S and P domains were determined to be 1.189 and 1.444, respectively, suggesting a positive selection existed. Fecal samples collected in different clinical phases from the two patients were all positive for Yu/1-CHN, suggesting a long existence of the virus in the host. It was indicated that immunocompromised patients may a reservoir for astrovirus, their excreta should be monitored even after discharge from hospital.}, }
@article {pmid32825440, year = {2020}, author = {Chen, YH and Wu, WK and Wu, MS}, title = {Microbiota-Associated Therapy for Non-Alcoholic Steatohepatitis-Induced Liver Cancer: A Review.}, journal = {International journal of molecular sciences}, volume = {21}, number = {17}, pages = {}, pmid = {32825440}, issn = {1422-0067}, mesh = {Animals ; Dysbiosis/complications ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Hepatitis/microbiology ; Humans ; Life Style ; Liver Neoplasms/*etiology/microbiology ; Non-alcoholic Fatty Liver Disease/*complications/*microbiology/*therapy ; Probiotics ; Weight Loss ; }, abstract = {Even though advancement in medicine has contributed to the control of many diseases to date, cancer therapy continues to pose several challenges. Hepatocellular carcinoma (HCC) etiology is multifactorial. Recently, non-alcoholic fatty liver disease (NAFLD) has been considered as an important risk factor of HCC. NAFLD can be divided into non-alcoholic simple fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) based on histopathological features. Recently, studies have indicated that the gut microbiota is associated with NAFLD and HCC. Therefore, in this review, we have discussed the effects of gut microbiota-related mechanisms, including dysbiosis and gut barrier function, and gut microbiota-derived metabolites on NAFLD and HCC pathogenesis and the potential therapeutic strategies for NAFLD and HCC. With a better understanding of the gut microbiota composition and function, new and improved diagnostic, prognostic, and therapeutic strategies for common liver diseases can be developed.}, }
@article {pmid32821439, year = {2020}, author = {Chen, H and Chen, Z and Shen, L and Wu, X and Ma, X and Lin, D and Zhang, M and Ma, X and Liu, Y and Wang, Z and Zhang, Y and Kuang, Z and Lu, Z and Li, X and Ma, L and Lin, X and Si, L and Chen, X}, title = {Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice.}, journal = {Cell death discovery}, volume = {6}, number = {}, pages = {75}, pmid = {32821439}, issn = {2058-7716}, abstract = {The significance of the microbiota-gut-brain axis has been increasingly recognized as a major modulator of autoimmunity. Here, we aim to characterize the gut microbiota of a large cohort of treatment-naïve anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis patients relative to that of healthy controls (HCs). Relative to HCs, anti-NMDAR encephalitis patients had a decreased microbiome alpha-diversity index, marked disturbances of gut microbial composition and intestinal permeability damage. Disturbed microbiota in anti-NMDAR encephalitis patients might be linked with different clinical characteristics. Imputed KEGG analysis revealed perturbations of functional modules in the gut microbiomes of anti-NMDAR encephalitis. Compared to HCs, microbiota-depleted mice receiving fecal microbiota transplantation (FMT) from anti-NMDAR encephalitis patients had hypersensitivity and cognitive impairment. Furthermore, anti-NMDAR encephalitis FMT mice showed altered T cells in the spleen and small intestine lamina propria with an increased Th17 cells. Overall, this study first suggests that the anti-NMDAR encephalitis microbiome itself can influence neurologic, Th17 response and behavioral function. The gut microbiota is a potential therapeutic target for anti-NMDAR encephalitis.}, }
@article {pmid32821067, year = {2020}, author = {Ghouri, YA and Tahan, V and Shen, B}, title = {Secondary causes of inflammatory bowel diseases.}, journal = {World journal of gastroenterology}, volume = {26}, number = {28}, pages = {3998-4017}, pmid = {32821067}, issn = {2219-2840}, mesh = {*Colitis, Ulcerative/therapy ; *Crohn Disease/therapy ; Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases/etiology/therapy ; *Pouchitis ; }, abstract = {Inflammatory bowel diseases (IBD), conventionally consist of Crohn's disease (CD) and ulcerative colitis. They occur in individuals with high risk genotype for the disease in the setting of appropriate environmental factors. The pathogenesis of IBD involves a dysregulated autoimmune response to gut dysbiosis, which in turn is triggered due to exposure to various inciting environmental factors. But there is no clearly defined etiology of IBD and this type of disease is termed as "idiopathic IBD", "classic IBD", or "primary IBD". We reviewed the current medical literature and found that certain etiological factors may be responsible for the development of IBD or IBD-like conditions, and we consider this form of de novo IBD as "secondary IBD". Currently known factors that are potentially responsible for giving rise to secondary IBD are medications; bowel altering surgeries and transplantation of organs, stem cells or fecal microbiome. Medications associated with the development of secondary IBD include; immunomodulators, anti-tumor necrosis factor alpha agents, anti-interleukin agents, interferons, immune stimulating agents and checkpoint inhibitors. Colectomy can in some cases give rise to de novo CD, pouchitis of the ileal pouch, or postcolectomy enteritis syndrome. After solid organ transplantation or hematopoietic stem cell transplantation, the recipient may develop de novo IBD or IBD flare. Fecal microbiota transplantation has been widely used to treat patients suffering from recurrent Clostridium difficile infection but can also causes IBD flares.}, }
@article {pmid32820707, year = {2020}, author = {Yiu, JHC and Chan, KS and Cheung, J and Li, J and Liu, Y and Wang, Y and Fung, WWL and Cai, J and Cheung, SWM and Dorweiler, B and Wan, EYF and Tso, P and Xu, A and Woo, CW}, title = {Gut Microbiota-Associated Activation of TLR5 Induces Apolipoprotein A1 Production in the Liver.}, journal = {Circulation research}, volume = {127}, number = {10}, pages = {1236-1252}, pmid = {32820707}, issn = {1524-4571}, mesh = {Animals ; Apolipoprotein A-I/genetics/*metabolism ; Cholesterol, HDL/metabolism ; Dietary Fats/metabolism ; Flagellin/metabolism/pharmacology ; *Gastrointestinal Microbiome ; Liver/*metabolism ; Mice ; NF-kappa B/metabolism ; Toll-Like Receptor 5/drug effects/*metabolism ; }, abstract = {RATIONALE: Dysbiosis of gut microbiota plays an important role in cardiovascular diseases but the molecular mechanisms are complex. An association between gut microbiome and the variance in HDL-C (high-density lipoprotein-cholesterol) level was suggested in a human study. Besides, dietary fat was shown to increase both HDL-C and LDL-C (low-density lipoprotein-cholesterol) levels. We speculate that certain types of gut bacteria responding to dietary fat may help to regulate HDL-C level and potentially affect atherosclerotic development.<br><br>OBJECTIVE: We aimed to investigate whether and how high-fat diet (HFD)-associated gut microbiota regulated HDL-C level.<br><br>METHODS AND RESULTS: We found that HFD increased gut flagellated bacteria population in mice. The increase in HDL-C level was adopted by mice receiving fecal microbiome transplantation from HFD-fed mouse donors. HFD led to increased hepatic but not circulating flagellin, and deletion of TLR5 (Toll-like receptor 5), a receptor sensing flagellin, suppressed HFD-stimulated HDL-C and ApoA1 (apolipoprotein A1) levels. Overexpression of TLR5 in the liver of TLR5-knockout mice was able to partially restore the production of ApoA1 and HDL-C levels. Mechanistically, TLR5 activation by flagellin in primary hepatocytes stimulated ApoA1 production through the transcriptional activation responding to the binding of NF-&#x3ba;B (nuclear factor-&#x3ba;B) on Apoa1 promoter region. Furthermore, oral supplementation of flagellin was able to stimulate hepatic ApoA1 production and HDL-C level and decrease atherosclerotic lesion size in apolipoprotein E-deficient (Apoe[-/-]) mice without triggering hepatic and systemic inflammation. The stimulation of ApoA1 production was also seen in human ApoA1-transgenic mice treated with oral flagellin.<br><br>CONCLUSIONS: Our finding suggests that commensal flagellated bacteria in gut can facilitate ApoA1 and HDL-C productions in liver through activation of TLR5 in hepatocytes. Hepatic TLR5 may be a potential drug target to increase ApoA1.}, }
@article {pmid32819434, year = {2020}, author = {Li, Y and Luo, ZY and Hu, YY and Bi, YW and Yang, JM and Zou, WJ and Song, YL and Li, S and Shen, T and Li, SJ and Huang, L and Zhou, AJ and Gao, TM and Li, JM}, title = {The gut microbiota regulates autism-like behavior by mediating vitamin B6 homeostasis in EphB6-deficient mice.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {120}, pmid = {32819434}, issn = {2049-2618}, mesh = {Animals ; Autism Spectrum Disorder/genetics/*metabolism/*microbiology/psychology ; Autistic Disorder/genetics/metabolism/microbiology/psychology ; Dopamine/metabolism ; *Gastrointestinal Microbiome/genetics ; *Homeostasis ; Male ; Mice ; Mice, Inbred C57BL ; Neural Inhibition ; Prefrontal Cortex/metabolism ; Receptors, Eph Family/*deficiency/genetics ; Social Behavior ; Vitamin B 6/*metabolism ; }, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a developmental disorder, and the effective pharmacological treatments for the core autistic symptoms are currently limited. Increasing evidence, particularly that from clinical studies on ASD patients, suggests a functional link between the gut microbiota and the development of ASD. However, the mechanisms linking the gut microbiota with brain dysfunctions (gut-brain axis) in ASD have not yet been full elucidated. Due to its genetic mutations and downregulated expression in patients with ASD, EPHB6, which also plays important roles in gut homeostasis, is generally considered a candidate gene for ASD. Nonetheless, the role and mechanism of EPHB6 in regulating the gut microbiota and the development of ASD are unclear.<br><br>RESULTS: Here, we found that the deletion of EphB6 induced autism-like behavior and disturbed the gut microbiota in mice. More importantly, transplantation of the fecal microbiota from EphB6-deficient mice resulted in autism-like behavior in antibiotic-treated C57BL/6J mice, and transplantation of the fecal microbiota from wild-type mice ameliorated the autism-like behavior in EphB6-deficient mice. At the metabolic level, the disturbed gut microbiota in EphB6-deficient mice led to vitamin B6 and dopamine defects. At the cellular level, the excitation/inhibition (E/I) balance in the medial prefrontal cortex was regulated by gut microbiota-mediated vitamin B6 in EphB6-deficient mice.<br><br>CONCLUSIONS: Our study uncovers a key role for the gut microbiota in the regulation of autism-like social behavior by vitamin B6, dopamine, and the E/I balance in EphB6-deficient mice, and these findings suggest new strategies for understanding and treating ASD. Video abstract.}, }
@article {pmid32818932, year = {2021}, author = {Waszkiewicz, N}, title = {Large Projects Investigating the Microbiota-Gut-Brain Axis and Fecal Transplant Studies Are Needed for Treating Mental Illnesses.}, journal = {Neuropsychobiology}, volume = {80}, number = {3}, pages = {276-278}, doi = {10.1159/000509573}, pmid = {32818932}, issn = {1423-0224}, mesh = {Brain ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Mental Disorders/therapy ; *Microbiota ; }, }
@article {pmid32817490, year = {2020}, author = {Britton, GJ and Contijoch, EJ and Spindler, MP and Aggarwala, V and Dogan, B and Bongers, G and San Mateo, L and Baltus, A and Das, A and Gevers, D and Borody, TJ and Kaakoush, NO and Kamm, MA and Mitchell, H and Paramsothy, S and Clemente, JC and Colombel, JF and Simpson, KW and Dubinsky, MC and Grinspan, A and Faith, JJ}, title = {Defined microbiota transplant restores Th17/RORγt[+] regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {35}, pages = {21536-21545}, pmid = {32817490}, issn = {1091-6490}, support = {R01 DK112296/DK/NIDDK NIH HHS/United States ; S10 OD026880/OD/NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; R01 GM108505/GM/NIGMS NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; R01 DK123749/DK/NIDDK NIH HHS/United States ; F31 DK112679/DK/NIDDK NIH HHS/United States ; T32 AI078892/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Colitis/prevention &amp; control ; Colon/microbiology ; Crohn Disease/metabolism/microbiology ; Cytokines/immunology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/immunology ; Humans ; Inflammatory Bowel Diseases/immunology/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/*immunology ; T-Lymphocytes, Regulatory/*immunology/microbiology ; Th17 Cells/*immunology/microbiology ; }, abstract = {The building evidence for the contribution of microbiota to human disease has spurred an effort to develop therapies that target the gut microbiota. This is particularly evident in inflammatory bowel diseases (IBDs), where clinical trials of fecal microbiota transplantation have shown some efficacy. To aid the development of novel microbiota-targeted therapies and to better understand the biology underpinning such treatments, we have used gnotobiotic mice to model microbiota manipulations in the context of microbiotas from humans with inflammatory bowel disease. Mice colonized with IBD donor-derived microbiotas exhibit a stereotypical set of phenotypes, characterized by abundant mucosal Th17 cells, a deficit in the tolerogenic RORγt[+] regulatory T (Treg) cell subset, and susceptibility to disease in colitis models. Transplanting healthy donor-derived microbiotas into mice colonized with human IBD microbiotas led to induction of RORγt[+] Treg cells, which was associated with an increase in the density of the microbiotas following transplant. Microbiota transplant reduced gut Th17 cells in mice colonized with a microbiota from a donor with Crohn's disease. By culturing strains from this microbiota and screening them in vivo, we identified a specific strain that potently induces Th17 cells. Microbiota transplants reduced the relative abundance of this strain in the gut microbiota, which was correlated with a reduction in Th17 cells and protection from colitis.}, }
@article {pmid32816876, year = {2021}, author = {Zhang, L and Roy, S}, title = {Opioid Modulation of the Gut-Brain Axis in Opioid-Associated Comorbidities.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {11}, number = {9}, pages = {}, pmid = {32816876}, issn = {2157-1422}, mesh = {Analgesics, Opioid/*pharmacology ; Brain-Gut Axis/*drug effects ; *Comorbidity ; Gastrointestinal Microbiome/*drug effects ; Hemostasis/drug effects ; Humans ; Neuroinflammatory Diseases/chemically induced/prevention &amp; control ; }, abstract = {Growing evidence from animal and human studies show that opioids have a major impact on the composition and function of gut microbiota. This leads to disruption in gut permeability and altered microbial metabolites, driving both systemic and neuroinflammation, which in turn impacts central nervous system (CNS) homeostasis. Tolerance and dependence are the major comorbidities associated with prolonged opioid use. Inflammatory mediators and signaling pathways have been implicated in both opioid tolerance and dependence. We provide evidence that targeting the gut microbiome during opioid use through prebiotics, probiotics, antibiotics, and fecal microbial transplantation holds the greatest promise for novel treatments for opioid abuse. Basic research and clinical trials are required to examine what is more efficacious to yield new insights into the role of the gut-brain axis in opioid abuse.}, }
@article {pmid32816619, year = {2020}, author = {Mitsinikos, FT and Chac, D and Schillingford, N and DePaolo, RW}, title = {Modifying macronutrients is superior to microbiome transplantation in treating nonalcoholic fatty liver disease.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1-16}, pmid = {32816619}, issn = {1949-0984}, mesh = {Animals ; Bacteria/classification/isolation &amp; purification ; Cytokines/metabolism ; *Diet, Fat-Restricted ; *Diet, Paleolithic ; Dietary Fiber/administration &amp; dosage ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Liver/immunology/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/*diet therapy/microbiology/pathology/therapy ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver injury and liver transplantation in Western countries. The pathogenesis of NAFLD includes overnutrition-associated metabolic syndrome or the improper consumption of dietary macro- and micro-nutrients that either support or prevent disease development. This altered nutrient landscape has been linked to shifts within the gut microbiota which can exacerbate liver pathology and the progression of NAFLD. Treatment goals for NAFLD target lifestyle and dietary modifications that restrict calories and adjust macronutrient content. It is not well understood how different macronutrients alter the microbiota and whether the diet-educated microbiota contribute to the resolution of disease. We fed mice a diet high in fat, cholesterol and fructose for 6 weeks and then in two different arms of the study, intervened with either a diet high in saturated and polyunsaturated fats and fiber or low in fats and fiber. In a second set of experiments, we performed microbiota transplants using cecal contents from mice fed one of the intervention diets to assess whether the diet-educated microbiota could impact clinical outcomes in mice fed a NAFLD-inducing diet. Pathology, steatosis, ALT/AST levels, and liver cytokine levels were measured as primary outcomes. We found that despite different microbiota compositions, both of the intervention diets reversed the progression of NAFLD and dampened inflammation. In contrast, transplantation of cecal contents from the intervention diet-fed mice to mice receiving a NAFLD-inducing diet was unable to prevent disease progression, and, in some cases, worsened disease. These data underscore the importance of dietary modifications to treat NAFLD and caution against the use of microbiota transplantation in the absence of dietary and lifestyle modifications.}, }
@article {pmid32814133, year = {2021}, author = {Yu, Z and Shi, Z and Zheng, Z and Han, J and Yang, W and Lu, R and Lin, W and Zheng, Y and Nie, D and Chen, G}, title = {DEHP induce cholesterol imbalance via disturbing bile acid metabolism by altering the composition of gut microbiota in rats.}, journal = {Chemosphere}, volume = {263}, number = {}, pages = {127959}, doi = {10.1016/j.chemosphere.2020.127959}, pmid = {32814133}, issn = {1879-1298}, mesh = {Animals ; Bacteroidetes/genetics ; Bile Acids and Salts/metabolism ; Cecum ; Cholesterol/*metabolism ; Diethylhexyl Phthalate/metabolism/*toxicity ; Firmicutes/genetics ; Gastrointestinal Microbiome/*drug effects ; Lipid Metabolism/genetics ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/metabolism ; Rats ; }, abstract = {Di(2-ethylhexyl) phthalate (DEHP) is one of the most widespread environmental contaminants worldwide because of its massive production, extensive use in common products, and liability to leach from products. This study investigated the mechanisms of DEHP mediated alteration of lipid metabolism. Rats were treated with 0.5 mg kg[-1] d[-1] of DEHP for 23 weeks. Results showed that the treatment induced cholesterol imbalance. Further fecal transplantation experiments corroborated the involvement of gut microbiota in DEHP-induced cholesterol imbalance. In addition, 16S rRNA gene sequencing analysis of cecal contents showed that DEHP disrupted the gut microbiota diversity in rats and increased the ratio of Firmicutes to Bacteroidetes. Further cecal metabolomic analyses, bile salt hydrolase enzyme activity, and gene expression examination revealed that chronic DEHP exposure generated a bile acid profile in the gut that is a more potent activator of farnesoid X receptor (FXR). The activation of FXR in the gut induced the expression of fibroblast growth factor 15, which subsequently suppressed cytochrome P450 family 7 subfamily A member 1 in the liver and bile acid synthesis. These results suggest that DEHP might induce cholesterol imbalance by regulating bile acid metabolism via the remodeling of the gut microbiota.}, }
@article {pmid32814026, year = {2020}, author = {Stephen-Victor, E and Crestani, E and Chatila, TA}, title = {Dietary and Microbial Determinants in Food Allergy.}, journal = {Immunity}, volume = {53}, number = {2}, pages = {277-289}, pmid = {32814026}, issn = {1097-4180}, support = {R01 AI126915/AI/NIAID NIH HHS/United States ; R21 AI132843/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Clostridiales/isolation &amp; purification ; Desensitization, Immunologic/methods ; *Diet ; Dysbiosis/*microbiology ; Food Hypersensitivity/*immunology ; Gastrointestinal Microbiome/*physiology ; Humans ; Immune Tolerance/immunology ; Immunoglobulin E/immunology ; Mice ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; T-Lymphocytes, Regulatory/cytology/immunology ; }, abstract = {The steep rise in food allergy (FA) has evoked environmental factors involved in disease pathogenesis, including the gut microbiota, diet, and their metabolites. Early introduction of solid foods synchronizes with the "weaning reaction," a time during which the microbiota imprints durable oral tolerance. Recent work has shown that children with FA manifest an early onset dysbiosis with the loss of Clostridiales species, which promotes the differentiation of ROR-γt[+] regulatory T cells to suppress FA. This process can be reversed in pre-clinical mouse models by targeted bacteriotherapy. Here, we review the dominant tolerance mechanisms enforced by the microbiota to suppress FA and discuss therapeutic intervention strategies that act to recapitulate the early life window of opportunity in stemming the FA epidemic.}, }
@article {pmid32812091, year = {2020}, author = {Kollmann, CT and Pretzsch, EB and Kunz, A and Isbert, C and Krajinovic, K and Reibetanz, J and Kim, M}, title = {Anorectal angle at rest predicting successful sacral nerve stimulation in idiopathic fecal incontinence-a cohort analysis.}, journal = {International journal of colorectal disease}, volume = {35}, number = {12}, pages = {2293-2299}, pmid = {32812091}, issn = {1432-1262}, mesh = {Anal Canal/diagnostic imaging ; *Electric Stimulation Therapy ; *Fecal Incontinence/diagnostic imaging/therapy ; Female ; Humans ; Lumbosacral Plexus/diagnostic imaging ; Retrospective Studies ; Treatment Outcome ; }, abstract = {PURPOSE: Sacral nerve stimulation is an effective treatment for patients suffering from fecal incontinence. However, less is known about predictors of success before stimulation. The purpose of this study was to identify predictors of successful sacral nerve stimulation in patients with idiopathic fecal incontinence.<br><br>METHODS: Consecutive female patients, receiving peripheral nerve evaluation and sacral nerve stimulation between September 2008 and October 2014, suffering from idiopathic fecal incontinence were included in this study. Preoperative patient's characteristics, anal manometry, and defecography results were collected prospectively and investigated by retrospective analysis. Main outcome measures were independent predictors of treatment success after sacral nerve stimulation.<br><br>RESULTS: From, all in all, 54 patients suffering from idiopathic fecal incontinence receiving peripheral nerve evaluation, favorable outcome was achieved in 23 of 30 patients after sacral nerve stimulation (per protocol 76.7%; intention to treat 42.6%). From all analyzed characteristics, wide anorectal angle at rest in preoperative defecography was the only independent predictor of favorable outcome in multivariate analysis (favorable 134.1 &#xb1; 13.9&#xb0; versus unfavorable 118.6 &#xb1; 17.1&#xb0;).<br><br>CONCLUSIONS: Anorectal angle at rest in preoperative defecography might present a predictor of outcome after sacral nerve stimulation in patients with idiopathic fecal incontinence.}, }
@article {pmid32811478, year = {2020}, author = {Then, CK and Paillas, S and Wang, X and Hampson, A and Kiltie, AE}, title = {Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation.}, journal = {BMC biology}, volume = {18}, number = {1}, pages = {102}, pmid = {32811478}, issn = {1741-7007}, support = {/WT_/Wellcome Trust/United Kingdom ; 23279/CRUK_/Cancer Research UK/United Kingdom ; 209397/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; C5255/A23755/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Bacteroides/*physiology/radiation effects ; Carcinoma/*radiotherapy ; Cell Line, Tumor ; Dietary Fiber/*administration &amp; dosage ; Female ; Gastrointestinal Microbiome/*radiation effects ; Humans ; Mice ; Mice, Nude ; Urinary Bladder Neoplasms/*radiotherapy ; }, abstract = {BACKGROUND: Patients with pelvic malignancies often receive radiosensitising chemotherapy with radiotherapy to improve survival; however, this is at the expense of increased normal tissue toxicity, particularly in elderly patients. Here, we explore if an alternative, low-cost, and non-toxic approach can achieve radiosensitisation in mice transplanted with human bladder cancer cells. Other investigators have shown slower growth of transplanted tumours in mice fed high-fibre diets. We hypothesised that mice fed a high-fibre diet would have improved tumour control following ionising radiation (IR) and that this would be mediated through the gut microbiota.<br><br>RESULTS: We investigated the effects of four different diets (low-fibre, soluble high-fibre, insoluble high-fibre, and mixed soluble/insoluble high-fibre diets) on tumour growth in immunodeficient mice implanted with human bladder cancer flank xenografts and treated with ionising radiation, simultaneously investigating the composition of their gut microbiomes by 16S rRNA sequencing. A significantly higher relative abundance of Bacteroides acidifaciens was seen in the gut (faecal) microbiome of the soluble high-fibre group, and the soluble high-fibre diet resulted in delayed tumour growth after irradiation compared to the other groups. Within the soluble high-fibre group, responders to irradiation had significantly higher abundance of B. acidifaciens than non-responders. When all mice fed with different diets were pooled, an association was found between the survival time of mice and relative abundance of B. acidifaciens. The gut microbiome in responders was predicted to be enriched for carbohydrate metabolism pathways, and in vitro experiments on the transplanted human bladder cancer cell line suggested a role for microbial-generated short-chain fatty acids and/or other metabolites in the enhanced radiosensitivity of the tumour cells.<br><br>CONCLUSIONS: Soluble high-fibre diets sensitised tumour xenografts to irradiation, and this phenotype was associated with modification of the microbiome and positively correlated with B. acidifaciens abundance. Our findings might be exploitable for improving radiotherapy response in human patients.}, }
@article {pmid32808030, year = {2021}, author = {Olesen, SW and Gerardin, Y}, title = {Re-Evaluating the Evidence for Faecal Microbiota Transplantation 'Super-Donors' in Inflammatory Bowel Disease.}, journal = {Journal of Crohn's &amp; colitis}, volume = {15}, number = {3}, pages = {453-461}, doi = {10.1093/ecco-jcc/jjaa170}, pmid = {32808030}, issn = {1876-4479}, mesh = {Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*therapy ; *Tissue Donors ; }, abstract = {BACKGROUND: Faecal microbiota transplantation [FMT] is a recommended treatment for recurrent Clostridioides difficile infection, and there is promise that FMT may be effective for conditions such as inflammatory bowel disease [IBD]. Previous FMT clinical trials have considered the possibility of a 'donor effect', that is, that FMT material from different donors has different clinical efficacies.<br><br>METHODS: Here we re-evaluate evidence for donor effects in published FMT clinical trials for IBD.<br><br>RESULTS: In ten of 12 published studies, no statistically significant donor effect was detected when rigorously re-evaluating the original analyses. One study showed statistically significant separation of microbiota composition of pools of donor stool when stratified by patient outcome. One study reported a significant effect but did not have underlying data available for re-evaluation. When quantifying the uncertainty on the magnitude of the donor effect, confidence intervals were large, including both zero donor effects and very substantial donor effects.<br><br>CONCLUSION: Although we found very little evidence for donor effects, the existing data cannot rule out the possibility that donor effects are clinically important. Large clinical trials prospectively designed to detect donor effects are probably needed to determine if donor effects are clinically relevant for IBD.}, }
@article {pmid32805128, year = {2020}, author = {Vandekerckhove, E and Janssens, F and Tate, D and De Looze, D}, title = {Treatment of Gut Fermentation Syndrome With Fecal Microbiota Transplantation.}, journal = {Annals of internal medicine}, volume = {173}, number = {10}, pages = {855}, doi = {10.7326/L20-0341}, pmid = {32805128}, issn = {1539-3704}, mesh = {Alcoholic Intoxication/etiology ; Anti-Bacterial Agents/*adverse effects ; Blood Alcohol Content ; Dietary Carbohydrates/*metabolism ; Ethanol/*metabolism ; *Fecal Microbiota Transplantation ; *Fermentation ; Gastric Bypass ; Gastrointestinal Diseases/chemically induced/microbiology/*therapy ; Gastrointestinal Microbiome/*drug effects ; Humans ; Liver Function Tests ; Male ; Middle Aged ; Syndrome ; }, }
@article {pmid32801142, year = {2020}, author = {van Lier, YF and Davids, M and Haverkate, NJE and de Groot, PF and Donker, ML and Meijer, E and Heubel-Moenen, FCJI and Nur, E and Zeerleder, SS and Nieuwdorp, M and Blom, B and Hazenberg, MD}, title = {Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients.}, journal = {Science translational medicine}, volume = {12}, number = {556}, pages = {}, doi = {10.1126/scitranslmed.aaz8926}, pmid = {32801142}, issn = {1946-6242}, mesh = {Fecal Microbiota Transplantation ; *Graft vs Host Disease/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Prospective Studies ; Transplant Recipients ; }, abstract = {Disruption of the intestinal microbiota occurs frequently in allogeneic hematopoietic cell transplantation (allo-HCT) recipients and predisposes them to development of graft-versus-host disease (GvHD). In a prospective, single-center, single-arm study, we investigated the effect of donor fecal microbiota transplantation (FMT) on symptoms of steroid-refractory or steroid-dependent, acute or late-onset acute intestinal GvHD in 15 individuals who had undergone allo-HCT. Study participants received a fecal suspension from an unrelated healthy donor via nasoduodenal infusion. Donor FMT was well tolerated, and infection-related adverse events did not seem to be related to the FMT procedure. In 10 of 15 study participants, a complete clinical response was observed within 1 month after FMT, without additional interventions to alleviate GvHD symptoms. This response was accompanied by an increase in gut microbial α-diversity, a partial engraftment of donor bacterial species, and increased abundance of butyrate-producing bacteria, including Clostridiales and Blautia species. In 6 of the 10 responding donor FMT recipients, immunosuppressant drug therapy was successfully tapered. Durable remission of steroid-refractory or steroid-dependent GvHD after donor FMT was associated with improved survival at 24 weeks after donor FMT. This study highlights the potential of donor FMT as a treatment for steroid-refractory or steroid-dependent GvHD, but larger clinical trials are needed to confirm the safety and efficacy of this procedure.}, }
@article {pmid32799901, year = {2020}, author = {Wang, S and Ishima, T and Zhang, J and Qu, Y and Chang, L and Pu, Y and Fujita, Y and Tan, Y and Wang, X and Hashimoto, K}, title = {Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve.}, journal = {Journal of neuroinflammation}, volume = {17}, number = {1}, pages = {241}, pmid = {32799901}, issn = {1742-2094}, support = {none//Smoking Research Foundation/ ; JP19dm0107119//Japan Agency for Medical Research and Development/ ; }, mesh = {Anhedonia/*drug effects ; Animals ; Anti-Bacterial Agents/*pharmacology ; Depression/blood/*microbiology ; Gastrointestinal Microbiome ; Interleukin-6/blood ; *Lactobacillus ; *Limosilactobacillus reuteri ; Mice ; Motor Activity/drug effects ; Stress, Psychological/blood/microbiology ; Vagus Nerve/*microbiology ; }, abstract = {BACKGROUND: The brain-gut-microbiota axis plays a role in the pathogenesis of stress-related disorders such as depression. In this study, we examined the effects of fecal microbiota transplantation (FMT) in mice with antibiotic-treated microbiota depletion.<br><br>METHODS: The fecal microbiota was obtained from mice subjected to chronic social defeat stress (CSDS) and control (no CSDS) mice. FMT from these two groups was performed to antibiotic-treated mice. 16S rRNA analysis was performed to examine the composition of gut microbiota. Furthermore, the effects of subdiaphragmatic vagotomy in depression-like phenotypes after ingestion of microbes were examined.<br><br>RESULTS: The ingestion of fecal microbiota from CSDS-susceptible mice resulted in an anhedonia-like phenotype, higher plasma levels of interleukin-6 (IL-6), and decreased expression of synaptic proteins in the prefrontal cortex (PFC) in antibiotic-treated mice but not in water-treated mice. 16S rRNA analysis suggested that two microbes (Lactobacillus intestinalis and Lactobacillus reuteri) may be responsible for the anhedonia-like phenotype in antibiotic-treated mice after FMT. Ingestion of these two microbes for 14&#x2009;days led to depression- and anhedonia-like phenotypes, higher plasma IL-6 levels, and decreased expression of synaptic proteins in the PFC of antibiotic-treated mice. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of behavioral abnormalities, elevation of plasma IL-6 levels, and downregulation of synaptic proteins in the PFC after ingestion of these two microbes.<br><br>CONCLUSIONS: These findings suggest that microbiota depletion using an antibiotic cocktail is essential for the development of FMT-induced behavioral changes and that the vagus nerve plays a key role in behavioral abnormalities in antibiotic-treated mice after the ingestion of L. intestinalis and L. reuteri. Therefore, it is likely that the brain-gut-microbiota axis participates in the pathogenesis of depression via the vagus nerve.}, }
@article {pmid32785703, year = {2020}, author = {Su, X and Yin, X and Liu, Y and Yan, X and Zhang, S and Wang, X and Lin, Z and Zhou, X and Gao, J and Wang, Z and Zhang, Q}, title = {Gut Dysbiosis Contributes to the Imbalance of Treg and Th17 Cells in Graves' Disease Patients by Propionic Acid.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {105}, number = {11}, pages = {}, doi = {10.1210/clinem/dgaa511}, pmid = {32785703}, issn = {1945-7197}, mesh = {Animals ; Disease Models, Animal ; Dysbiosis/complications/*immunology/metabolism ; Gastrointestinal Microbiome/*immunology ; Graves Disease/complications/*immunology/metabolism ; Humans ; Metabolomics ; Mice ; Propionates/metabolism ; T-Lymphocytes, Regulatory/*immunology ; Th17 Cells/*immunology ; }, abstract = {BACKGROUND: Graves' disease (GD) is a typical organ-specific autoimmune disease. Intestinal flora plays a pivotal role in immune homeostasis and autoimmune disease development. However, the association and mechanism between intestinal flora and GD remain elusive.<br><br>OBJECTIVE: To investigate the association and mechanism between intestinal flora and GD.<br><br>METHODS: We recruited 58 initially untreated GD patients and 63 healthy individuals in the study. The composition and metabolic characteristics of the intestinal flora in GD patients and the causal relationship between intestinal flora and GD pathogenesis were assessed using 16S rRNA gene sequencing, targeted/untargeted metabolomics, and fecal microbiota transplantation.<br><br>RESULTS: The composition, metabolism, and inter-relationships of the intestinal flora were also changed, particularly the significantly reduced short-chain fatty acid (SCFA)-producing bacteria and SCFAs. The YCH46 strain of Bacteroides fragilis could produce propionic acid and increase Treg cell numbers while decreasing Th17 cell numbers. Transplanting the intestinal flora of GD patients significantly increased GD incidence in the GD mouse model. Additionally, there were 3 intestinal bacteria genera (Bacteroides, Alistipes, Prevotella) could distinguish GD patients from healthy individuals with 85% accuracy.<br><br>CONCLUSIONS: Gut dysbiosis contributes to a Treg/Th17 imbalance through the pathway regulated by propionic acid and promotes the occurrence of GD, together with other pathogenic factors. Bacteroides, Alistipes, and Prevotella have great potential to serve as adjunct markers for GD diagnosis. This study provided valuable clues for improving immune dysfunction of GD patients using B. fragilis and illuminated the prospects of microecological therapy for GD as an adjunct treatment.}, }
@article {pmid32774464, year = {2020}, author = {Barberio, B and Facchin, S and Mele, E and D'Incà, R and Sturniolo, GC and Farinati, F and Zingone, F and Quagliariello, A and Ghisa, M and Massimi, D and Casadei, C and Savarino, EV}, title = {Faecal microbiota transplantation in Clostridioides difficile infection: real-life experience from an academic Italian hospital.}, journal = {Therapeutic advances in gastroenterology}, volume = {13}, number = {}, pages = {1756284820934315}, pmid = {32774464}, issn = {1756-283X}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a reasonable therapeutic option for the treatment of Clostridioides difficile infection (CDI) recurrent and refractory (RCDI) to therapy, but little evidence on the long-term impact of this therapy is currently available in the literature. The aim of this study was to evaluate the efficacy and safety of FMT in recurrent and refractory CDI and the modifications of the recipient's gut microbiota in the medium-long term.<br><br>METHODS: This prospective study collects the clinical and laboratory data of RCDI patients treated with FMT by colonoscopy from February 2016 to October 2019. Stool samples for metagenomic analysis were collected pre-FMT at 1&#x2009;week and at 6 and 12-24&#x2009;months post-FMT.<br><br>RESULTS: In the study period, 20 FMT procedures were performed on 19 patients. Overall, FMT was effective in 85% of treated patients. No serious adverse event was recorded. In the medium- to long-term follow up, a newly diagnosed case of collagenous colitis was observed. Post-FMT, significant changes in microbiota were observed, characterised by the transition from a low- to a greater-diversity profile. Therefore, FMT restores eubiosis and maintains it over time.<br><br>CONCLUSION: FMT is a safe and effective treatment option in RCDI patients. This procedure induces profound microbiota changes that explain its high clinical efficacy.}, }
@article {pmid32773765, year = {2020}, author = {Zhang, Q and Lu, Q and Luo, Y}, title = {Fecal Microbiota Transplantation and Detection of Prevalence of IgA-Coated Bacteria in the Gut.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {161}, pages = {}, doi = {10.3791/60772}, pmid = {32773765}, issn = {1940-087X}, mesh = {Animals ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunoglobulin A/*metabolism ; Mice ; Prevalence ; }, abstract = {Gut microbiota exert pleiotropic roles in human health and disease. Fecal microbiota transplantation (FMT) is an effective method to investigate the biological function of intestinal bacteria as a whole or at the species level. Several different FMT methods have been published. Here, we present an FMT protocol that successfully depletes gut microbiota in a matter of days, followed by transplantation of fecal microbiota from fresh or frozen donor intestinal contents to conventional mice. Real time-PCR is applied to test the efficacy of bacterial depletion. Sequencing of the 16S ribosomal RNA (rRNA) is then applied to test the relative abundance and identity of gut microbiota in recipient mice. We also present a flow cytometry-based detection method of immunoglobulin A (IgA)-coated bacteria in the gut.}, }
@article {pmid32772900, year = {2020}, author = {Halverson, T and Alagiakrishnan, K}, title = {Gut microbes in neurocognitive and mental health disorders.}, journal = {Annals of medicine}, volume = {52}, number = {8}, pages = {423-443}, pmid = {32772900}, issn = {1365-2060}, mesh = {Cognition/drug effects/physiology ; Combined Modality Therapy/methods ; Dysbiosis/complications/microbiology/physiopathology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Mental Disorders/microbiology/physiopathology/*therapy ; Mental Health ; Probiotics/*administration &amp; dosage ; Psychotropic Drugs/adverse effects ; Treatment Outcome ; }, abstract = {INTRODUCTION: As individuals age, the prevalence of neurocognitive and mental health disorders increases. Current biomedical treatments do not completely address the management of these conditions. Despite new pharmacological therapy the challenges of managing these diseases remain.There is increasing evidence that the Gut Microbiome (GM) and microbial dysbiosis contribute to some of the more prevalent mental health and neurocognitive disorders, such as depression, anxiety, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), schizophrenia, bipolar disorder (BP), and dementia as well as the behavioural and psychological symptoms of dementia (BPSD) through the microbiota-gut-brain axis. Methodology: Scoping review about the effect of gut microbiota on neurocognitive and mental health disorders.<br><br>RESULTS: This scoping review found there is an evolving evidence of the involvement of the gut microbiota in the pathophysiology of neurocognitive and mental health disorders. This manuscript also discusses how the psychotropics used to treat these conditions may have an antimicrobial effect on GM, and the potential for new strategies of management with probiotics and faecal transplantation.<br><br>CONCLUSIONS: This understanding can open up the need for a gut related approach in these disorders as well as unlock the door for the role of gut related microbiota management. KEY MESSAGES Challenges of managing mental health conditions remain in spite of new pharmacological therapy. Gut dysbiosis is seen in various mental health conditions. Various psychotropic medications can have an influence on the gut microbiota by their antimicrobial effect.}, }
@article {pmid32772456, year = {2020}, author = {Bueno, F and Albert, E and Giménez, E and Piñana, JL and Pérez, A and Gómez, MD and Hernández-Boluda, JC and Gonzalez-Barberá, EM and Montoro, J and Guerreiro, M and Balaguer-Roselló, A and Hernani, R and Sanz, J and Solano, C and Navarro, D}, title = {Cytomegalovirus DNA load monitoring in stool specimens for anticipating the occurrence of intestinal acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: Is it of any value?.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {22}, number = {6}, pages = {e13440}, doi = {10.1111/tid.13440}, pmid = {32772456}, issn = {1399-3062}, support = {201810//Abbott Laboratories/ ; }, mesh = {Adult ; Cytomegalovirus/genetics ; *Cytomegalovirus Infections/complications ; DNA, Viral/*isolation &amp; purification ; Feces/virology ; *Graft vs Host Disease/diagnosis ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Intestinal Diseases/diagnosis ; Prospective Studies ; *Viral Load ; }, abstract = {BACKGROUND: Data have been published suggesting a bidirectional interaction between cytomegalovirus (CMV) infection and acute graft-versus-host disease (aGvHD) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Here, we hypothesized that prospective CMV DNA monitoring in stool specimens may be useful for predicting subsequent occurrence of intestinal aGvHD (IaGvHD).<br><br>METHODS: This two-center study enrolled 121 consecutive adult patients undergoing any modality of allo-HSCT. A total of 1,009 stool specimens were collected (a median of 7 specimens/patient; range, 1-18). CMV DNA monitoring in stools and plasma was performed using real-time PCR assays.<br><br>RESULTS: CMV DNA was detected in stools in 20 patients (cumulative incidence, 16.9%; 95% CI, 6.3%-31.8%). Median CMV DNA level in stool specimens was 1,258&#xa0;IU/0.1g (range, 210-4,087&#xa0;IU/0.1&#xa0;g). All these patients and their donors were CMV seropositive, and 16 of the 20 patients also had CMV DNAemia, while 4 patients had CMV DNA detected in stools without CMV DNAemia. No correlation was found between CMV DNA loads in plasma and stools (P&#xa0;=&#xa0;.40). Prior CMV DNAemia, aGvHD, or IaGvHD were not associated with presence of CMV DNA in feces. IaGvHD was present in 30 patients, in 5 of whom CMV DNA was detected in stools. Neither detection of CMV DNA in feces nor in plasma was associated with subsequent IaGvHD (OR, 0.67; 95% CI, 0.18-2.52; P&#xa0;=&#xa0;.55 and OR, 0.86; 95% CI, 0.38-1.96; P&#xa0;=&#xa0;.71, respectively). No patient in this cohort had CMV end-organ disease within the study period.<br><br>CONCLUSION: Our study failed to provide evidence pointing to a reciprocal interaction between GI CMV infection and IaGvHD. CMV DNA monitoring in stools seems of no value to anticipate occurrence of IaGvHD.}, }
@article {pmid32772093, year = {2020}, author = {Sood, A and Singh, A and Mahajan, R and Midha, V and Kaur, K and Singh, D and Bansal, N and Dharni, K}, title = {Clinical Predictors of response to Faecal Microbiota Transplantation in patients with active ulcerative colitis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjaa163}, pmid = {32772093}, issn = {1876-4479}, abstract = {BACKGROUND: Fecal Microbiota Transplantation (FMT) has been shown to be effective for induction of remission in patients with active ulcerative colitis (UC). At present, clinical factors impacting the response to FMT in UC remain unclear.<br><br>METHODS: Patients with active UC treated with multisession FMT via colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22, were analysed. Response to FMT was defined as achievement of corticosteroid free clinical remission at week 30. Patient and disease characteristics were evaluated to determine the predictors of response to FMT.<br><br>RESULTS: Out of 140 patients with active UC treated with FMT, 93 patients [mean age 34.96&#xb1;11.27 years, 62.36% males (n=58), mean Mayo clinic score 8.07&#xb1;2.00] who completed the multi-session FMT protocol were analysed. Fifty-seven (61.29%) patients achieved clinical remission. Younger age (OR for age 0.93, 95% CI 0.89-0.97, p=0.001), moderate (Mayo clinic score 6-9) disease severity (OR 3.01, 95% CI 1.12&#xa0;to&#xa0;8.06, p=0.025) and endoscopic Mayo score 2 (OR 5.55, 95% CI 2.18-14.06, p<0.001) were significant predictors of remission on univariate analysis. Younger age, disease extent E2 and endoscopic mayo score 2 (OR 0.925, 95% CI 0.88-0.97, p=0.002; OR 2.89, 95% CI 1.01-8.25, p=0.04 and OR 8.43, 95% CI 2.38-29.84, p=0.001, respectively) were associated with clinical remission on multivariate logistic regression. A mathematical model (nomogram) was developed for estimating the probability of remission with FMT protocol.<br><br>CONCLUSION: Younger age, disease extent E2, and endoscopic mayo score 2 significantly predict achievement of clinical remission with FMT in active UC. The prediction model can help in selecting individuals for FMT. Validation in larger cohorts is needed.}, }
@article {pmid32769886, year = {2020}, author = {He, Y and Xu, R and Wang, W and Zhang, J and Hu, X}, title = {Probiotics, prebiotics, antibiotic, Chinese herbal medicine, and fecal microbiota transplantation in irritable bowel syndrome: Protocol for a systematic review and network meta-analysis.}, journal = {Medicine}, volume = {99}, number = {32}, pages = {e21502}, pmid = {32769886}, issn = {1536-5964}, mesh = {Adolescent ; Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Bayes Theorem ; Drugs, Chinese Herbal/*therapeutic use ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Male ; Middle Aged ; Network Meta-Analysis ; Prebiotics/*administration &amp; dosage ; Probiotics/*therapeutic use ; Randomized Controlled Trials as Topic ; Research Design ; Systematic Reviews as Topic ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease, with a high global incidence, which seriously influences the quality of life and work efficiency of patients. Extensive research showed that IBS is related to changes in the intestinal microenvironment. The novel treatment strategy targeting the gut microbiota is being actively implemented. Probiotics, antibiotics, prebiotics, fecal microbiota transplantation, and Chinese Herbal Medicine have been proven to be effective in the treatment of IBS, and all have an impact on the intestinal flora of patients. However, these 5 treatments have their own pros and cons and have not been systematically evaluated and compared. Therefore, this study will indirectly compare the safety and effectiveness of these 5 methods in the treatment of IBS through network meta-analysis.<br><br>METHODS: The following databases including Embase, Pubmed, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, WHO International Clinical Trials Registry Platform and ClinicalTrials.gov will be retrieved from inception to June 2020 without language restrictions. Literature selection, data extraction, and bias analysis will be done by 2 researchers. The primary outcome is global symptoms improvement. The secondary outcomes will include individual IBS symptom scores, emotional response, and adverse events. The conventional pair-wise meta-analysis will be performed using Stata V.14.0 and be pooled using a random-effects model. We will use WinBUGS V.1.4.3 (Cambridge, United Kingdom) with a Bayesian hierarchical random-effects model to conduct the network meta-analysis.<br><br>RESULTS: This study will provide systematic reviews and indirect network comparison results about treatments of IBS.<br><br>CONCLUSIONS: This study will systematically evaluate and compare 5 intestinal flora-related therapies for IBS and to provide an evidence-based medical decision-making basis for clinicians.<br><br>TRIAL REGISTRATION NUMBER: INPLASY202050047.}, }
@article {pmid32768944, year = {2020}, author = {Wang, H and Yang, F and Xin, R and Cui, D and He, J and Zhang, S and Sun, Y}, title = {The gut microbiota attenuate neuroinflammation in manganese exposure by inhibiting cerebral NLRP3 inflammasome.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {129}, number = {}, pages = {110449}, doi = {10.1016/j.biopha.2020.110449}, pmid = {32768944}, issn = {1950-6007}, mesh = {Amyloid beta-Peptides/metabolism ; Animals ; Cerebral Cortex/*metabolism/pathology ; Cytokines/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Inflammasomes/*metabolism ; Intestines/*microbiology ; Male ; Manganese Poisoning/*metabolism/microbiology/pathology/prevention &amp; control ; NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism ; Peptide Fragments/metabolism ; Rats, Sprague-Dawley ; tau Proteins/metabolism ; }, abstract = {Manganese (Mn) exposure has been reported to cause neurodegenerative disorders. β-Amyloid (Aβ) induced Tau pathology in an NLRP3-dependent manner is at the heart of Alzheimer's and Parkinson's diseases. The gut microbiota plays a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities. In this study, we found that Mn exposure increases Aβ1-40 and Tau production in brain, and causes hippocampal degeneration and necrosis. Meanwhile, Mn exposure can stimulate neurotoxicity by increasing inflammation either in peripheral blood and CNS. Importantly, we found that transplantation of gut microbiota from normal rats into Mn exposure rats reduced Aβ and Tau expression, and the cerebral expression of NLRP3 was downregulated, and the expression of neuroinflammatory factors was also downregulated. Therefore, improving the composition of gut microbiota in Mn exposure rats can attenuate neuroinflammation, which is considered as a novel therapeutic strategy for Mn exposure by remodelling the gut microbiota.}, }
@article {pmid32768560, year = {2020}, author = {Magdy, M and Fahmy, A and Zaki, NI and Mohamed, AK}, title = {Prophylactic versus therapeutic role of the transplanted CD34[+] Umbilical Cord Blood Stem Cells and Wharton Jelly Mesenchymal Stem Cells in early / acute hepatic S. mansoni granulomas reversal in mice; a novel approach.}, journal = {Experimental parasitology}, volume = {217}, number = {}, pages = {107938}, doi = {10.1016/j.exppara.2020.107938}, pmid = {32768560}, issn = {1090-2449}, mesh = {Animals ; Anthelmintics/administration &amp; dosage ; Antigens, CD34/*blood ; *Cord Blood Stem Cell Transplantation ; Feces/parasitology ; Fetal Blood/cytology ; Flow Cytometry ; Granuloma/prevention &amp; control/therapy ; Humans ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Liver/pathology ; Liver Diseases, Parasitic/prevention &amp; control/therapy ; Male ; Mesenchymal Stem Cells ; Mice ; Octamer Transcription Factor-3 ; Parasite Egg Count ; Praziquantel/administration &amp; dosage ; Schistosomiasis mansoni/*prevention &amp; control/*therapy ; Staining and Labeling ; Transforming Growth Factor beta ; }, abstract = {PURPOSE: Praziquantel (PZQ) is the conventional antibilharzial agent. Nevertheless, no antibilharzial prophylactic agents or 100% curable therapy approved and no reported data about use of human CD34[+] Umbilical Cord Blood Stem Cells (CD34[+]UCBSCs) or Wharton Jelly Mesenchymal Stem Cells (WJMSCs) in prevention and/or complete eradication of acute S.mansoni granulomas in liver. We aimed to study possible prophylactic vs therapeutic role of human CD34[+]UCBSCs and WJMSCs in acute hepatic bilharzial granulomas in pre vs post-infected mice.<br><br>METHODS: Seventy mice were divided into 7 groups (10 mice each): Normal, S.mansoni-infected, post-infected PZQ-treated, CD34[+]UCBSCs pre and post-infected, WJMSCs pre and post-infected. Serological, parasitological, histopathological evaluation using OCT4 &amp; TGFB immunohistochemistry and quantitative image analysis assessment of TGFB-stained fibrogenesis in liver granulomas performed.<br><br>RESULTS: Histopathologically, surprisingly and significantly, the prophylactic pre-infection stem cells (CD34[+]UCBSCs and WJMSCs) &amp; similarly the post-infection CD34[+]UCBSCs treatment revealed eradication/reversal of the entire granulomas and no fibrosis. Moreover, post-infection PZQ treatment showed fewer and significantly smaller granulomas than post-infection WJMSCs treatment. Nevertheless, post-infection WJMSCs exhibited non-significant less TGFB-stained fibrogenesis.<br><br>CONCLUSION: CD34[+]UCBSCs exerted the best prophylactic and therapeutic roles in prevention and complete cure of acute hepatic S.mansoni granulomas over WJMSCs and PZQ. In contrast, only pre-infection WJMSCs exhibited similar preventive (prophylactic) effect. On the contrary, post-infection WJMSCs were the worst (incompletely reversed granulomas). Post-infection Praziquantel was overall better therapeutically than WJMSCs in this regard. Accordingly, when it comes to WJMSCs application, WJMSCs are better used as a pre-infection prophylactic and preventive tool rather than a post-infection therapy. Further studies are needed.}, }
@article {pmid32767183, year = {2020}, author = {Tan, GSE and Tay, HL and Tan, SH and Lee, TH and Ng, TM and Lye, DC}, title = {Gut Microbiota Modulation: Implications for Infection Control and Antimicrobial Stewardship.}, journal = {Advances in therapy}, volume = {37}, number = {10}, pages = {4054-4067}, pmid = {32767183}, issn = {1865-8652}, mesh = {*Antimicrobial Stewardship ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Infection Control ; *Microbiota ; }, abstract = {The human microbiome comprises a complex ecosystem of microbial communities that exist within the human body, the largest and most diverse of which are found within the human intestine. It has been increasingly implicated in human health and diseases, demonstrably playing a critical role in influencing host immune response, protection against pathogen overgrowth, biosynthesis, and metabolism. As our understanding of the links between the gut microbiota with host immunity and infectious diseases deepens, there is a greater need to incorporate methods of modulating it as a means of therapy or infection prevention in daily clinical practice. Traditional antimicrobial stewardship principles have been evaluated to assess their impact on the gut microbiota diversity and the consequent repercussions, taking into consideration antibiotic pharmacokinetic and pharmacodynamic properties. Novel strategies of selective digestive decontamination and fecal microbiota transplantation to regulate the gut microbiota have also been tested in different conditions with variable results. This review seeks to provide an overview of the available literature on the modulation of the gut microbiota and its implications for infection control and antimicrobial stewardship. With increased understanding, gut microbiota profiling through metataxonomic analysis may provide further insight into modulating microbial communities in the context of infection prevention and control.}, }
@article {pmid32765600, year = {2020}, author = {Yang, CQ and Guo, XS and Ji-Li,  and Wei, ZB and Zhao, L and Zhao, GT and Sheng, ST}, title = {Rifaximin Improves Visceral Hyperalgesia via TRPV1 by Modulating Intestinal Flora in the Water Avoidance Stressed Rat.}, journal = {Gastroenterology research and practice}, volume = {2020}, number = {}, pages = {4078681}, pmid = {32765600}, issn = {1687-6121}, abstract = {BACKGROUND: Rifaximin is effective in relieving pain symptoms with IBS patients, although the mechanisms were not clear. The aims of the research were to investigate whether the visceral hyperalgesia was alleviated by rifaximin via TRPV1 channel in rats.<br><br>METHODS: Rats were subjected to water avoidance stress (WAS) and were pretreated with rifaximin by oral gavage. The visceromotor response to colorectal distension was measured. The changes of TRPV1 in peripheral and central neurons of rats were detected by immunofluorescence, western blot method, and RT-PCR. Bacterial 16S ribosomal DNA in ileal contents was assessed using the Illumina MiSeq platform. The effect of intestinal flora on TRPV1 channel was observed by fecal microbiota transplantation (FMT) methods.<br><br>RESULTS: Rifaximin could relieve the visceral hyperalgesia and reduce the TRPV1 expression of neurons and ileum mucosa in rats induced by WAS. The reduced relative abundance of intestinal flora induced by WAS could be partly prevented by rifaximin. The electromyographical activities and immunoreactivity of TRPV1 in rats could be changed after FMT.<br><br>CONCLUSIONS: Rifaximin could improve visceral hyperalgesia via TRPV1 channels of peripheral and central neurons by modulating intestinal flora in rats.}, }
@article {pmid32764526, year = {2020}, author = {Alagna, L and Palomba, E and Mangioni, D and Bozzi, G and Lombardi, A and Ungaro, R and Castelli, V and Prati, D and Vecchi, M and Muscatello, A and Bandera, A and Gori, A}, title = {Multidrug-Resistant Gram-Negative Bacteria Decolonization in Immunocompromised Patients: A Focus on Fecal Microbiota Transplantation.}, journal = {International journal of molecular sciences}, volume = {21}, number = {16}, pages = {}, pmid = {32764526}, issn = {1422-0067}, mesh = {Clostridium Infections/microbiology/therapy ; Drug Resistance, Multiple/*genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Dysbiosis/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*genetics ; Gram-Negative Bacteria/genetics ; Humans ; Immunocompromised Host/genetics/immunology ; }, abstract = {Antimicrobial resistance is an important issue for global health; in immunocompromised patients, such as solid organ and hematological transplant recipients, it poses an even bigger threat. Colonization by multidrug-resistant (MDR) bacteria was acknowledged as a strong risk factor to subsequent infections, especially in individuals with a compromised immune system. A growing pile of studies has linked the imbalance caused by the dominance of certain taxa populating the gut, also known as intestinal microbiota dysbiosis, to an increased risk of MDR bacteria colonization. Several attempts were proposed to modulate the gut microbiota. Particularly, fecal microbiota transplantation (FMT) was successfully applied to treat conditions like Clostridioides difficile infection and other diseases linked to gut microbiota dysbiosis. In this review we aimed to provide a look at the data gathered so far on FMT, focusing on its possible role in treating MDR colonization in the setting of immunocompromised patients and analyzing its efficacy and safety.}, }
@article {pmid32764281, year = {2020}, author = {Arias, N and Arboleya, S and Allison, J and Kaliszewska, A and Higarza, SG and Gueimonde, M and Arias, JL}, title = {The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases.}, journal = {Nutrients}, volume = {12}, number = {8}, pages = {}, pmid = {32764281}, issn = {2072-6643}, support = {PSI2017-83893-R//Ministerio de Ciencia e Innovaci&#xf3;n/ ; PSI2015-73111-EXP//Ministerio de Econom&#xed;a y Competitividad/ ; PSI2017-90806-REDT//Ministerio de Econom&#xed;a y Competitividad/ ; AGL2017-83653R//Ministerio de Econom&#xed;a y Competitividad/ ; IJCI-2017-32156//Ministerio de Ciencia e Innovaci&#xf3;n/ ; }, mesh = {Animals ; Biological Availability ; Cardiovascular Diseases/*metabolism ; Choline/genetics/*metabolism/pharmacokinetics ; Diet/methods ; Dysbiosis/metabolism ; *Gastrointestinal Microbiome ; Genotype ; Humans ; Inflammatory Bowel Diseases/metabolism ; Liver/metabolism ; Methylamines/*metabolism ; Non-alcoholic Fatty Liver Disease/*metabolism ; Renal Insufficiency, Chronic/*metabolism ; }, abstract = {Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon absorption by the host is converted into trimethylamine-N-oxide (TMAO) in the liver. A high accumulation of both components is related to cardiovascular disease, inflammatory bowel disease, non-alcoholic fatty liver disease, and chronic kidney disease. However, the relationship between the microbiota production of these components and its impact on these diseases still remains unknown. In this review, we will address which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., the genotype) and diet affect TMA production, and the colonization of these microbes and the reversal of dysbiosis as a therapy for these diseases.}, }
@article {pmid32762536, year = {2020}, author = {Witkowski, M and Weeks, TL and Hazen, SL}, title = {Gut Microbiota and Cardiovascular Disease.}, journal = {Circulation research}, volume = {127}, number = {4}, pages = {553-570}, pmid = {32762536}, issn = {1524-4571}, support = {P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Atherosclerosis/etiology ; Bile Acids and Salts/metabolism ; Cardiovascular Diseases/blood/*microbiology ; Carnitine/metabolism ; Choline/metabolism ; Disease Models, Animal ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Glutamine/*analogs &amp; derivatives/blood/metabolism ; Host Microbial Interactions/physiology ; Humans ; Methylamines/blood/*metabolism ; Mice ; Mice, Inbred C57BL ; Signal Transduction ; Thrombosis/etiology ; Vasculitis/etiology ; }, abstract = {Fecal microbial community changes are associated with numerous disease states, including cardiovascular disease (CVD). However, such data are merely associative. A causal contribution for gut microbiota in CVD has been further supported by a multitude of more direct experimental evidence. Indeed, gut microbiota transplantation studies, specific gut microbiota-dependent pathways, and downstream metabolites have all been shown to influence host metabolism and CVD, sometimes through specific identified host receptors. Multiple metaorganismal pathways (involving both microbe and host) both impact CVD in animal models and show striking clinical associations in human studies. For example, trimethylamine N-oxide and, more recently, phenylacetylglutamine are gut microbiota-dependent metabolites whose blood levels are associated with incident CVD risks in large-scale clinical studies. Importantly, a causal link to CVD for these and other specific gut microbial metabolites/pathways has been shown through numerous mechanistic animal model studies. Phenylacetylglutamine, for example, was recently shown to promote adverse cardiovascular phenotypes in the host via interaction with multiple ARs (adrenergic receptors)-a class of key receptors that regulate cardiovascular homeostasis. In this review, we summarize recent advances of microbiome research in CVD and related cardiometabolic phenotypes that have helped to move the field forward from associative to causative results. We focus on microbiota and metaorganismal compounds/pathways, with specific attention paid to short-chain fatty acids, secondary bile acids, trimethylamine N-oxide, and phenylacetylglutamine. We also discuss novel therapeutic strategies for directly targeting the gut microbiome to improve cardiovascular outcomes.}, }
@article {pmid32760481, year = {2020}, author = {Namba, Y and Hirata, Y and Mukai, S and Nishida, T and Ishikawa, S and Kai, A and Kohata, A and Okimoto, S and Fujisaki, S and Fukuda, S and Takahashi, M and Fukuda, T}, title = {Multiple peritoneal dissemination of T2 colorectal cancer without lymph node metastases: a case report.}, journal = {Journal of surgical case reports}, volume = {2020}, number = {7}, pages = {rjaa118}, pmid = {32760481}, issn = {2042-8812}, abstract = {Most cases of peritoneal dissemination of colorectal cancers are from T3 or T4 tumors. A 61-year-old woman was admitted for examination of a positive fecal occult blood test. Colonoscopy showed an ascending colon tumor that was diagnosed as an adenocarcinoma with massive submucosal invasion. Imaging modality revealed numerous nodules throughout the abdominal cavity. Peritoneal dissemination of the ascending colon or ovarian cancer and pseudomyxoma peritonei were considered in the preoperative differential diagnoses, and laparoscopic ileocecal resection was performed. Intraperitoneal observation revealed numerous white nodules in the peritoneum, omentum and Douglas fossa. Both the nodules and tumor were diagnosed as mucinous carcinoma based on a pathology report. The tumor invasion depth was limited to muscularis propria, and no regional lymph node metastasis was detected. Peritoneal dissemination of the ascending colon cancer was considered. We report a rare case of multiple peritoneal dissemination of T2 colorectal cancer without lymph node metastases.}, }
@article {pmid32760391, year = {2020}, author = {Jouhten, H and Ronkainen, A and Aakko, J and Salminen, S and Mattila, E and Arkkila, P and Satokari, R}, title = {Cultivation and Genomics Prove Long-Term Colonization of Donor's Bifidobacteria in Recurrent Clostridioides difficile Patients Treated With Fecal Microbiota Transplantation.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1663}, pmid = {32760391}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) and it's also considered for treating other indications. Metagenomic studies have indicated that commensal donor bacteria may colonize FMT recipients, but cultivation has not been employed to verify strain-level colonization. We combined molecular profiling of Bifidobacterium populations with cultivation, molecular typing, and whole genome sequencing (WGS) to isolate and identify strains that were transferred from donors to recipients. Several Bifidobacterium strains from two donors were recovered from 13 recipients during the 1-year follow-up period after FMT. The strain identities were confirmed by WGS and comparative genomics. Our results show that specific donor-derived bifidobacteria can colonize rCDI patients for at least 1 year, and thus FMT may have long-term consequences for the recipient's microbiota and health. Conceptually, we demonstrate that FMT trials combined with microbial profiling can be used as a platform for discovering and isolating commensal strains with proven colonization capacity for potential therapeutic use.}, }
@article {pmid32756350, year = {2020}, author = {Mańkowska-Wierzbicka, D and Stelmach-Mardas, M and Gabryel, M and Tomczak, H and Skrzypczak-Zielińska, M and Zakerska-Banaszak, O and Sowińska, A and Mahadea, D and Baturo, A and Wolko, &#x141; and Słomski, R and Dobrowolska, A}, title = {The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study.}, journal = {Biomedicines}, volume = {8}, number = {8}, pages = {}, pmid = {32756350}, issn = {2227-9059}, support = {502-01-222-38-000//grant for young scientists from Poznan University of Medical Sciences, Poznan, Poland/ ; }, abstract = {The modification of the microbiome through fecal microbiota transplantation (FMT) is becoming a very promising therapeutic option for inflammatory bowel disease (IBD) patients. Our pilot study aimed to assess the effectiveness of multi-session FMT treatment in active ulcerative colitis (UC) patients. Ten patients with UC were treated with multi-session FMT (200 mL) from healthy donors, via colonoscopy/gastroscopy. Patients were evaluated as follows: at baseline, at week 7, and after 6 months, routine blood tests (including C reactive protein (CRP) and calprotectin) were performed. 16S rRNA gene (V3V4) sequencing was used for metagenomic analysis. The severity of UC was classified based on the Truelove-Witts index. The assessment of microbial diversity showed significant differences between recipients and healthy donors. FMT contributed to long-term, significant clinical and biochemical improvement. Metagenomic analysis revealed an increase in the amount of Lactobacillaceaea, Micrococcaceae, Prevotellaceae, and TM7 phylumsp.oral clone EW055 during FMT, whereas Staphylococcaceae and Bacillaceae declined significantly. A positive increase in the proportion of the genera Bifidobacterium, Lactobacillus, Rothia, Streptococcus, and Veillonella and a decrease in Bacillus, Bacteroides, and Staphylococcus were observed based on the correlation between calprotectin and Bacillus and Staphylococcus; ferritin and Lactobacillus, Veillonella, and Bifidobacterium abundance was indicated. A positive change in the abundance of Firmicutes was observed during FMT and after 6 months. The application of multi-session FMT led to the restoration of recipients' microbiota and resulted in the remission of patients with active UC.}, }
@article {pmid32755639, year = {2020}, author = {Holmes, A and Finger, C and Morales-Scheihing, D and Lee, J and McCullough, LD}, title = {Gut dysbiosis and age-related neurological diseases; an innovative approach for therapeutic interventions.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {226}, number = {}, pages = {39-56}, pmid = {32755639}, issn = {1878-1810}, support = {R01 NS077769/NS/NINDS NIH HHS/United States ; R01 NS094543/NS/NINDS NIH HHS/United States ; R01 NS103592/NS/NINDS NIH HHS/United States ; RF1 AG058463/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*pathology ; Brain/pathology ; Dysbiosis/*microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Nervous System Diseases/*microbiology/pathology ; }, abstract = {The gut microbiota is a complex ecosystem of bacteria, fungi, and viruses that acts as a critical regulator in microbial, metabolic, and immune responses in the host organism. Imbalances in the gut microbiota, termed "dysbiosis," often induce aberrant immune responses, which in turn disrupt the local and systemic homeostasis of the host. Emerging evidence has highlighted the importance of gut microbiota in intestinal diseases, and more recently, in age-related central nervous systems diseases, for example, stroke and Alzheimer's disease. It is now generally recognized that gut microbiota significantly influences host behaviors and modulates the interaction between microbiota, gut, and brain, via the "microbiota-gut-brain axis." Several approaches have been utilized to reduce age-related dysbiosis in experimental models and in clinical studies. These include strategies to manipulate the microbiome via fecal microbiota transplantation, administration of prebiotics and probiotics, and dietary interventions. In this review, we explore both clinical and preclinical therapies for treating age-related dysbiosis.}, }
@article {pmid32755385, year = {2020}, author = {Bernardazzi, C and Xu, H and Tong, H and Laubitz, D and Figliuolo da Paz, V and Curiel, L and Ghishan, FK}, title = {An indisputable role of NHE8 in mucosal protection.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {319}, number = {4}, pages = {G421-G431}, pmid = {32755385}, issn = {1522-1547}, support = {R01DK3023890/GF/NIH HHS/United States ; }, mesh = {Animals ; Butyrates/metabolism ; Butyric Acid/administration &amp; dosage ; Colon/microbiology ; Dysbiosis/etiology/microbiology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Goblet Cells/drug effects/physiology ; HT29 Cells ; Humans ; Intestinal Mucosa/*physiology ; Lactobacillus/physiology ; Mice ; Mice, Knockout ; Mucins/biosynthesis ; Probiotics/administration &amp; dosage ; Sodium-Hydrogen Exchangers/deficiency/*physiology ; }, abstract = {The loss of the intestinal Na[+]/H[+] exchanger isoform 8 (NHE8) results in an ulcerative colitis-like condition with reduction of mucin production and dysbiosis, indicating that NHE8 plays an important role in intestinal mucosal protection. The aim of this study was to investigate the potential rebalance of the altered microbiota community of NHE8-deficient mice via fecal microbiota transplantation (FMT) and feeding probiotic VSL#3. We also aimed to stimulate mucin production by sodium butyrate administration via enema. Data from 16S rRNA sequencing showed that loss of NHE8 contributes to colonic microbial dysbiosis with reduction of butyrate-producing bacteria. FMT increased bacterial adhesion in the colon in NHE8 knockout (NHE8KO) mice. Periodic-acid Schiff reagent (PAS) stain and quantitative PCR showed no changes in mucin production during FMT. In mice treated with the probiotic VSL#3, a reduction of Lactobacillus and segmented filamentous bacteria (SFB) in NHE8KO mouse colon was detected and an increase in goblet cell theca was observed. In NHE8KO mice receiving sodium butyrate (NaB), 1 mM NaB stimulated Muc2 expression without changing goblet cell theca, but 10 mM NaB induced a significant reduction of goblet cell theca without altering Muc2 expression. Furthermore, 5 mM and 10 mM NaB-treated HT29-MTX cells displayed increased apoptosis, while 0.5 mM NaB stimulated Muc2 gene expression. These data showed that loss of NHE8 leads to dysbiosis with reduction of butyrate-producing bacteria and FMT and VSL#3 failed to rebalance the microbiota in NHE8KO mice. Therefore, FMT, VSL#3, and NaB are not able to restore mucin production in the absence of NHE8 in the intestine.NEW &amp; NOTEWORTHY Loss of Na[+]/H[+] exchanger isoform 8 (NHE8), a Slc9 family of exchanger that contributes to sodium uptake, cell volume regulation, and intracellular pH homeostasis, resulted in dysbiosis with reduction of butyrate-producing bacteria and decrease of Muc2 production in the intestine in mice. Introducing fecal microbiota transplantation (FMT) and VSL#3 in NHE8 knockout (NHE8KO) mice failed to rebalance the microbiota in these mice. Furthermore, administration of FMT, VSL#3, and sodium butyrate was unable to restore mucin production in the absence of NHE8 in the intestine.}, }
@article {pmid32754917, year = {2020}, author = {Mohammed, A and Alghetaa, HK and Zhou, J and Chatterjee, S and Nagarkatti, P and Nagarkatti, M}, title = {Protective effects of Δ[9] -tetrahydrocannabinol against enterotoxin-induced acute respiratory distress syndrome are mediated by modulation of microbiota.}, journal = {British journal of pharmacology}, volume = {177}, number = {22}, pages = {5078-5095}, pmid = {32754917}, issn = {1476-5381}, support = {R01AI129788//NIH grants/ ; P20GM103641//NIH grants/ ; R01 AI129788/AI/NIAID NIH HHS/United States ; P20 GM103641/GM/NIGMS NIH HHS/United States ; P01 AT003961/AT/NCCIH NIH HHS/United States ; R01 AT006888/AT/NCCIH NIH HHS/United States ; P01AT003961//NIH grants/ ; R01AT006888//NIH grants/ ; R01 ES030144/ES/NIEHS NIH HHS/United States ; R01AI123947//NIH grants/ ; R01ES030144//NIH grants/ ; R01 AI123947/AI/NIAID NIH HHS/United States ; //Ministry of Higher Education and Scientific Research (MOHESR), Iraq/ ; }, mesh = {Animals ; Clostridiales ; Cytokines ; Dronabinol/pharmacology ; Enterotoxins ; *Gastrointestinal Microbiome ; Mice ; *Respiratory Distress Syndrome/chemically induced ; }, abstract = {BACKGROUND AND PURPOSE: Staphylococcal enterotoxin-B (SEB) is one of the most potent bacterial superantigens that exerts profound toxic effects by inducing a cytokine storm. Inhaled SEB can cause acute respiratory distress syndrome (ARDS), which is often fatal and with no effective treatments.<br><br>EXPERIMENTAL APPROACH: Efficacy of &#x394;[9] -tetrahydrocannabinol (THC) was tested in a mouse model of SEB-mediated ARDS, in which lung inflammation, alterations in gut/lung microbiota and production of short-chain fatty acids (SCFAs) was measured. Gene dysregulation of lung epithelial cells was studied by transcriptome arrays. Faecal microbiota transplantation (FMT) was performed to confirm the role of microbiota in suppressing ARDS.<br><br>KEY RESULTS: While SEB triggered ARDS and 100% mortality in mice, THC protected the mice from fatality. Pyrosequencing analysis revealed that THC caused significant and similar alterations in microbiota in the lungs and gut of mice exposed to SEB. THC significantly increased the abundance of beneficial bacterial species, Ruminococcus gnavus, but decreased pathogenic microbiota, Akkermansia muciniphila. FMT confirmed that THC-mediated reversal of microbial dysbiosis played crucial role in attenuation of SEB-mediated ARDS. THC treatment caused an increase in SCFA, of which propionic acid was found to inhibit the inflammatory response. Transcriptome array showed that THC up-regulated several genes like lysozyme1 and lysozyme2, &#x3b2;-defensin-2, claudin, zonula-1, occludin-1, Mucin2 and Muc5b while down-regulating &#x3b2;-defensin-1.<br><br>CONCLUSION AND IMPLICATIONS: The study demonstrates for the first time that THC attenuates SEB-mediated ARDS and toxicity by altering the microbiota in the lungs and the gut as well as promoting antimicrobial and anti-inflammatory pathways.}, }
@article {pmid32751239, year = {2020}, author = {Perillo, F and Amoroso, C and Strati, F and Giuffrè, MR and Díaz-Basabe, A and Lattanzi, G and Facciotti, F}, title = {Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes.}, journal = {International journal of molecular sciences}, volume = {21}, number = {15}, pages = {}, pmid = {32751239}, issn = {1422-0067}, support = {IG-2019 22923//Associazione Italiana per la Ricerca sul Cancro/ ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Biological Products/therapeutic use ; Colorectal Neoplasms/immunology/microbiology/pathology/*therapy ; Dysbiosis/immunology/microbiology/pathology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Host Microbial Interactions/immunology ; Humans ; Neoplasm Recurrence, Local/immunology/microbiology/pathology/*therapy ; Prebiotics/administration &amp; dosage ; Probiotics/*therapeutic use ; Tumor Microenvironment/drug effects/immunology ; }, abstract = {Colorectal cancer (CRC) is a multifaceted disease influenced by both environmental and genetic factors. A large body of literature has demonstrated the role of gut microbes in promoting inflammatory responses, creating a suitable microenvironment for the development of skewed interactions between the host and the gut microbiota and cancer initiation. Even if surgery is the primary therapeutic strategy, patients with advanced disease or cancer recurrence after surgery remain difficult to cure. Therefore, the gut microbiota has been proposed as a novel therapeutic target in light of recent promising data in which it seems to modulate the response to cancer immunotherapy. The use of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics, and fecal microbiota transplantation, is therefore considered to support current therapies in CRC management. In this review, we will discuss the importance of host-microbe interactions in CRC and how promoting homeostatic immune responses through microbe-targeted therapies may be useful in preventing/treating CRC development.}, }
@article {pmid32750174, year = {2021}, author = {Bajaj, JS and Gavis, EA and Fagan, A and Wade, JB and Thacker, LR and Fuchs, M and Patel, S and Davis, B and Meador, J and Puri, P and Sikaroodi, M and Gillevet, PM}, title = {A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder.}, journal = {Hepatology (Baltimore, Md.)}, volume = {73}, number = {5}, pages = {1688-1700}, doi = {10.1002/hep.31496}, pmid = {32750174}, issn = {1527-3350}, support = {R21 TR002024/TR/NCATS NIH HHS/United States ; I01 CX001761/CX/CSRD VA/United States ; }, mesh = {Aged ; Alcohol Drinking/epidemiology ; Alcoholism/*therapy ; Craving ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Surveys and Questionnaires ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Alcohol use disorder (AUD) is associated with microbial alterations that worsen with cirrhosis. Fecal microbiota transplant (FMT) could be a promising approach.<br><br>APPROACH AND RESULTS: In this phase 1, double-blind, randomized clinical trial, patients with AUD-related cirrhosis with problem drinking (AUDIT-10&#xa0;>&#xa0;8) were randomized 1:1 into receiving one placebo or FMT enema from a donor enriched in Lachnospiraceae and Ruminococcaceae. Six-month safety was the primary outcome. Alcohol craving questionnaire, alcohol consumption (urinary ethylglucuronide/creatinine), quality of life, cognition, serum IL-6 and lipopolysaccharide-binding protein, plasma/stool short-chain fatty acids (SCFAs), and stool microbiota were tested at baseline and day 15. A 6-month follow-up with serious adverse event (SAE) analysis was performed. Twenty patients with AUD-related cirrhosis (65&#xa0;&#xb1;&#xa0;6.4&#xa0;years, all men, Model for End-Stage Liver Disease 8.9&#xa0;&#xb1;&#xa0;2.7) with similar demographics, cirrhosis, and AUD severity were included. Craving reduced significantly in 90% of FMT versus 30% in placebo at day 15 (P&#xa0;=&#xa0;0.02) with lower urinary ethylglucuronide/creatinine (P&#xa0;=&#xa0;0.03) and improved cognition and psychosocial quality of life. There was reduction in serum IL-6 and lipopolysaccharide-binding protein and increased butyrate/isobutyrate compared with baseline in FMT but not placebo. Microbial diversity increased with higher Ruminococcaceae and other SCFAs, producing taxa following FMT but not placebo, which were linked with SCFA levels. At 6&#xa0;months, patients with any SAEs (8 vs. 2, P&#xa0;=&#xa0;0.02), AUD-related SAEs (7 vs. 1, P&#xa0;=&#xa0;0.02), and SAEs/patient (median [interquartile range], 1.5 [1.25] vs. 0 [0.25] in FMT, P&#xa0;=&#xa0;0.02) were higher in placebo versus FMT.<br><br>CONCLUSIONS: This phase 1 trial shows that FMT is safe and associated with short-term reduction in alcohol craving and consumption with favorable microbial changes versus placebo in patients with alcohol-associated cirrhosis with alcohol misuse. There was also a reduction in AUD-related events over 6&#xa0;months in patients assigned to FMT.}, }
@article {pmid32749642, year = {2020}, author = {Baryah, ANS and Midha, V and Mahajan, R and Sood, A}, title = {Impact of Corona Virus Disease-19 (COVID-19) pandemic on gastrointestinal disorders.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {39}, number = {3}, pages = {214-219}, pmid = {32749642}, issn = {0975-0711}, mesh = {Betacoronavirus/isolation &amp; purification ; COVID-19 ; Comorbidity ; *Coronavirus Infections/epidemiology/prevention &amp; control ; *Gastrointestinal Diseases/epidemiology/immunology/therapy ; Humans ; *Immunomodulation ; *Pandemics/prevention &amp; control ; *Pneumonia, Viral/epidemiology/prevention &amp; control ; SARS-CoV-2 ; }, abstract = {Worldwide, several hospitals in different regions and countries have been affected with Corona Virus Disease-19 (COVID-19). All medical specialties including gastroenterology are impacted by COVID-19. Here, we review the bidirectional comorbidity of chronic gastrointestinal (GI) disorders and COVID-19, including the incidence and outcome of COVID-19 in individuals with various GI disorders and the impact of COVID-19 on the course and outcome of the underlying (or comorbid) GI disorders. Currently, there is no evidence that COVID-19 is more (or less) frequent in comorbid GI disorders. It is also reassuring that the outcome of COVID-19 is unaffected by the underlying GI disorder or its treatment, though potential concerns remain in regard to the use of immunomodulatory treatments in inflammatory bowel disease (IBD) and liver transplant recipients. Despite these concerns, there is now agreement among experts that ongoing immunomodulatory treatments may not be interrupted in individuals with IBD during the COVID-19 pandemic. Caution, however, may be exercised with the use of corticosteroids in the management of IBD. In addition, COVID-19 does not appear to impact the manifestations, course, outcome, and treatment of comorbid GI disorders, e.g. IBD. Decompensation of liver cirrhosis is, however, possible during COVID-19 episodes. A direct concern, however, might relate to the potential transmission of the virus through fecal microbiota transplants.}, }
@article {pmid32742991, year = {2020}, author = {Yue, YY and Fan, XY and Zhang, Q and Lu, YP and Wu, S and Wang, S and Yu, M and Cui, CW and Sun, ZR}, title = {Bibliometric analysis of subject trends and knowledge structures of gut microbiota.}, journal = {World journal of clinical cases}, volume = {8}, number = {13}, pages = {2817-2832}, pmid = {32742991}, issn = {2307-8960}, abstract = {BACKGROUND: Gut microbiota is an emerging field of research, with related research having breakthrough development in the past 15 years. Bibliometric analysis can be applied to analyze the evolutionary trends and emerging hotspots in this field.<br><br>AIM: To study the subject trends and knowledge structures of gut microbiota related research fields from 2004 to 2018.<br><br>METHODS: The literature data on gut microbiota were identified and downloaded from the PubMed database. Through biclustering analysis, strategic diagrams, and social network analysis diagrams, the main trend and knowledge structure of research fields concerning gut microbiota were analyzed to obtain and compare the research hotspots in each period.<br><br>RESULTS: According to the strategic coordinates and social relationship network map, Clostridium Infections/microbiology, Clostridium Infections/therapy, RNA, Ribosomal, 16S/genetics, Microbiota/genetics, Microbiota/immunology, Dysbiosis/immunology, Infla-mmation/immunology, Fecal Microbiota Transplantation/methods, Fecal Microbiota Transplantation can be used as an emerging research hotspot in the past 5 years (2014-2018).<br><br>CONCLUSION: Some subjects were not yet fully studied according to the strategic coordinates; and the emerging hotspots in the social network map can be considered as directions of future research.}, }
@article {pmid32742177, year = {2020}, author = {Abhyankar, D and McKee, KT and Vukojevic, P}, title = {Gut Microbiota and Response to Immunotherapeutic Drugs in Oncology: More Questions Than Answers.}, journal = {Clinical Medicine Insights. Oncology}, volume = {14}, number = {}, pages = {1179554920933868}, pmid = {32742177}, issn = {1179-5549}, abstract = {Immuno-oncology drugs (IODs) have revolutionized the treatment of some cancers. Although IODs are enabling some patients with cancer to become long-time survivors, only 30% to 40% respond to these drugs. There is experimental and clinical evidence that the gut microbiome may play a role in IOD response, leading to speculation that manipulation of the gut microenvironment might improve the response rate to IODs. We review the evidence relating to how gut microorganisms may affect response to IODs and discuss the implications of targeting the microbiome to improve IOD response, including the challenges to refine and translate the findings to practical clinical use.}, }
@article {pmid32741315, year = {2021}, author = {Tai, FWD and Ellul, P and Elosua, A and Fernandez-Urien, I and Tontini, GE and Elli, L and Eliakim, R and Kopylov, U and Koo, S and Parker, C and Panter, S and Sidhu, R and McAlindon, M}, title = {Panenteric capsule endoscopy identifies proximal small bowel disease guiding upstaging and treatment intensification in Crohn's disease: A European multicentre observational cohort study.}, journal = {United European gastroenterology journal}, volume = {9}, number = {2}, pages = {248-255}, pmid = {32741315}, issn = {2050-6414}, mesh = {Adult ; Biomarkers/blood ; C-Reactive Protein/metabolism ; *Capsule Endoscopy/adverse effects ; Crohn Disease/blood/drug therapy/*pathology/*therapy ; Female ; Humans ; Inflammation ; Intestinal Mucosa/pathology ; Intestine, Small/*pathology ; Leukocyte L1 Antigen Complex/blood ; Male ; Severity of Illness Index ; }, abstract = {BACKGROUND: Endoscopically defined mucosal healing in Crohn's disease is associated with improved outcomes. Panenteric capsule endoscopy enables a single non-invasive assessment of small and large bowel mucosal inflammation.<br><br>AIMS AND METHODS: This multicentre observational study of patients with suspected and established Crohn's disease examined the feasibility, safety and impact on patient outcomes of panenteric capsule endoscopy in routine clinical practice. The potential role in assessment of disease severity and extent by a comparison with existing clinical and biochemical markers is examined.<br><br>RESULTS: Panenteric capsule endoscopy was performed on 93 patients (71 with established and 22 with suspected Crohn's disease). A complete examination occurred in 85% (79/93). Two cases (2.8%) of capsule retention occurred in patients with established Crohn's disease. Panenteric capsule resulted in management change in 38.7% (36/93) patients, including 64.6% (32/48) of those with an established diagnosis whose disease was active, and all three patients with newly diagnosed Crohn's disease. Montreal classification was upstaged in 33.8% of patients with established Crohn's disease and mucosal healing was demonstrated in 15.5%. Proximal small bowel disease upstaged disease in 12.7% and predicted escalation of therapy (odds ratio 40.3, 95% confidence interval 3.6-450.2). Raised C-reactive protein and faecal calprotectin were poorly sensitive in detecting active disease (0.48 and 0.59 respectively).<br><br>CONCLUSIONS: Panenteric capsule endoscopy was feasible in routine practice and the ability to detect proximal small bowel disease may allow better estimation of prognosis and guide treatment intensification. Panenteric capsule endoscopy may be a suitable non-invasive endoscopic investigation in determining disease activity and supporting management decisions.}, }
@article {pmid32739967, year = {2020}, author = {Guery, B and Barbut, F and Tschudin-Sutter, S}, title = {Diagnostic and therapy of severe Clostridioides difficile infections in the ICU.}, journal = {Current opinion in critical care}, volume = {26}, number = {5}, pages = {450-458}, doi = {10.1097/MCC.0000000000000753}, pmid = {32739967}, issn = {1531-7072}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Humans ; Intensive Care Units ; }, abstract = {PURPOSE OF REVIEW: The purpose of the review is to provide all the recent data focusing on the diagnostic and treatment of Clostridioides difficile infection in patients admitted in the ICU.<br><br>RECENT FINDINGS: In the ICU, diagnosis remains complicated with a large number of alternative diagnosis. The treatment classically relies on vancomycin but fidaxomicin and fecal microbiota transplantation are now potential solutions in selected indications.<br><br>SUMMARY: Data on ICU-related CDI remain limited and conflicting. To date, there is no unique and simple way to obtain a diagnosis for CDI, the combination of clinical signs and a two-step testing algorithm remains the recommended gold-standard. Two molecules can be proposed for first line treatment: vancomycin and fidaxomicin. Although metronidazole may still be discussed as a treatment option for mild CDI in low-risk patients, its use for ICU-patients does not seem reasonable. Several reports suggest that fecal microbiota transplantation could be discussed, as it is well tolerated and associated with a high rate of clinical cure. CDI is a dynamic and active area of research with new diagnostic techniques, molecules, and management concepts likely changing our approach to this old disease in the near future.}, }
@article {pmid32738249, year = {2020}, author = {Allegretti, JR and Kelly, CR and Grinspan, A and Mullish, BH and Kassam, Z and Fischer, M}, title = {Outcomes of Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Diseases and Recurrent Clostridioides difficile Infection.}, journal = {Gastroenterology}, volume = {159}, number = {5}, pages = {1982-1984}, doi = {10.1053/j.gastro.2020.07.045}, pmid = {32738249}, issn = {1528-0012}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; P30 DK034854/DK/NIDDK NIH HHS/United States ; /DH_/Department of Health/United Kingdom ; MC_PC_12025/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/diagnosis/microbiology/*therapy ; Colitis, Ulcerative/diagnosis/microbiology/*therapy ; Crohn Disease/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Prospective Studies ; Reinfection ; Treatment Outcome ; United States ; Young Adult ; }, }
@article {pmid32737354, year = {2020}, author = {Wasinger, VC and Lu, K and Yau, YY and Nash, J and Lee, J and Chang, J and Paramsothy, S and Kaakoush, NO and Mitchell, HM and Leong, RWL}, title = {Spp24 is associated with endocytic signalling, lipid metabolism, and discrimination of tissue integrity for 'leaky-gut' in inflammatory bowel disease.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {12932}, pmid = {32737354}, issn = {2045-2322}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers ; Colitis, Ulcerative/*blood/pathology/therapy ; *Endocytosis ; Fecal Microbiota Transplantation ; Female ; Humans ; Intestinal Mucosa/*metabolism/pathology ; *Lipid Metabolism ; Male ; Middle Aged ; Phosphoproteins/*blood ; *Signal Transduction ; }, abstract = {Epithelial barrier injury allows contaminants to cross-over into the blood stream and trigger an inflammatory response, contributing to inflammatory bowel disease (IBD). Currently there is no single test that can reliably diagnose intestinal mucosal barrier function or measure impaired epithelial cell integrity associated with increasing permeability. Here, we assess the association between serum proteins and small intestinal permeability as detected by confocal laser endomicroscopy (CLE); in particular the known IBD marker-secreted phosphoprotein 24 (SPP24) and its binding partners; and use developed monoclonal antibodies to assess the role of SPP24 in mucosal healing. Sera were obtained from 28 IBD patients and non-IBD controls undergoing CLE with scores ranging from low to high permeability, as well as active ulcerative colitis from 53 patients undergoing fecal microbiota transplant therapy (FMT). Higher permeability associated with altered lipid metabolism, heightened innate immune response and junctional protein signalling in UC patients. A correlation between increasing leak and SPP24 peptide was observed. There is a strong indication of the novel role of SPP24 in gut barrier dysfunction particularly in ulcerative colitis. Its correlation to the established CLE for monitoring permeability has the potential to provide a blood based parallel to monitor and guide therapy more readily across a broad spectrum of illnesses for which 'leak' dominates the pathology.}, }
@article {pmid32737051, year = {2020}, author = {Kurin, M and Cooper, G}, title = {Irritable bowel syndrome with diarrhea: Treatment is a work in progress.}, journal = {Cleveland Clinic journal of medicine}, volume = {87}, number = {8}, pages = {501-511}, doi = {10.3949/ccjm.87a.19011}, pmid = {32737051}, issn = {1939-2869}, mesh = {Antidepressive Agents/therapeutic use ; Antidiarrheals/therapeutic use ; Cognitive Behavioral Therapy ; Combined Modality Therapy ; Diarrhea/etiology/*therapy ; Diet/methods ; Dietary Fiber/therapeutic use ; Fecal Microbiota Transplantation ; Gastrointestinal Agents ; Humans ; Irritable Bowel Syndrome/complications/*therapy ; Melatonin/therapeutic use ; Mentha piperita ; Plant Oils/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {Irritable bowel syndrome (IBS) is a heterogeneous functional disease with a high prevalence and significant impact on quality of life. Traditionally understood as a pure disorder of brain-gut interaction, it is increasingly clear that IBS encompasses diverse pathologies, some of which involve objective alterations of intestinal structure, function, and the microbiome. IBS is subclassified as diarrhea, constipation, or mixed type based on the most prominent stool form. We review the diagnosis and management of the diarrheal type through a pathophysiologic lens, with attention to recent developments that can inform a mechanistically based targeted approach to treatment.}, }
@article {pmid32732062, year = {2021}, author = {Yamamoto, Y and Miyagawa, Y and Kitazawa, M and Tanaka, H and Kuroiwa, M and Hondo, N and Koyama, M and Nakamura, S and Tokumaru, S and Muranaka, F and Soejima, Y}, title = {Association of feces sign with prognosis of non-emergency adhesive small bowel obstruction.}, journal = {Asian journal of surgery}, volume = {44}, number = {1}, pages = {292-297}, doi = {10.1016/j.asjsur.2020.07.012}, pmid = {32732062}, issn = {0219-3108}, mesh = {Age Factors ; Aged ; *Eating ; Fasting ; *Feces ; Female ; Humans ; Intestinal Obstruction/*diagnosis/diagnostic imaging/physiopathology/*therapy ; *Intestine, Small ; Intubation, Gastrointestinal ; Length of Stay ; Leukocyte Count ; Male ; Middle Aged ; Patient Discharge ; Prognosis ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: /Objective: The feces sign has been reported as a possible predictive factor for non-operative treatment of small bowel obstruction. However, its relationship with prognosis of non-emergency adhesive small bowel obstruction remains unclear. This study aimed to clarify the relationship between the feces sign and prognosis of non-emergency adhesive small bowel obstruction.<br><br>METHODS: Ninety-two patients with non-emergency adhesive small bowel obstruction with the transitional zone visible on computed tomography were included. Patients were categorized into two groups: feces sign positive (n&#xa0;=&#xa0;40) and negative (n&#xa0;=&#xa0;52). Clinical features and prognosis were compared between the two groups. Cox proportional hazards regression models incorporating the feces sign were used to analyze odds of diet resumption and discharge.<br><br>RESULTS: Patients with feces sign were younger (p&#xa0;=&#xa0;0.015), had a higher body mass index (p&#xa0;=&#xa0;0.027), and a lower white blood cell count (p&#xa0;=&#xa0;0.019) on admission. More patients with feces sign were successfully treated with fasting and/or nasogastric tube placement (p&#xa0;<&#xa0;0.001), and no patient with feces sign suffered from recurrent obstruction after diet resumption. Kaplan-Meier analysis showed that patients with feces sign took less time for diet resumption (p&#xa0;=&#xa0;0.007) and discharge (p&#xa0;=&#xa0;0.004) than those without it. Using Cox proportional hazards regression model, the feces sign was reported as an independent predictor of diet resumption (odds ratio 1.685, p&#xa0;=&#xa0;0.018) and discharge (odds ratio 1.861, p&#xa0;=&#xa0;0.007).<br><br>CONCLUSIONS: The feces sign is associated with improved odds for diet resumption and discharge.}, }
@article {pmid32729978, year = {2020}, author = {Lu, JF and Zhu, MQ and Zhang, H and Liu, H and Xia, B and Wang, YL and Shi, X and Peng, L and Wu, JW}, title = {Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high-fat diet-fed mice.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {34}, number = {9}, pages = {12053-12071}, doi = {10.1096/fj.201903102RR}, pmid = {32729978}, issn = {1530-6860}, mesh = {Animals ; Bacteroidetes/*growth &amp; development ; Diet, High-Fat/*adverse effects ; Firmicutes/*growth &amp; development ; Gastrointestinal Microbiome/*drug effects ; Hesperidin/*analogs &amp; derivatives/pharmacology ; Male ; Mice ; *Obesity/chemically induced/drug therapy/microbiology ; }, abstract = {Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier, and chronic inflammation. Neohesperidin (Neo), a natural polyphenol abundant in citrus fruits, is known for its preventative and therapeutic effects on numerous diseases. Here, we report that Neo administration attenuates weight gain, low-grade inflammation, and insulin resistance in mice fed high-fat diet (HFD). Also, Neo administration substantially restores gut barrier damage, metabolic endotoxemia, and systemic inflammation. Sequencing of 16S rRNA genes in fecal samples revealed that Neo administration reverses HFD-induced intestinal microbiota dysbiosis: an increase in the diversity of gut microbiota and alteration in the composition of intestinal microbiota (particularly in the relative abundances of Bacteroidetes and Firmicutes). Furthermore, systemic antibiotic treatment abolishes the beneficial effects of Neo in body weight control, suggesting that the effect of Neo on obesity attenuation largely depends on the gut microbiota. More importantly, we demonstrate that the impact of Neo on the regulation of obesity could be transferred from Neo-treated mice to HFD-fed mice via fecal microbiota transplantation. Collectively, our data highlight the efficacy of Neo as a prebiotic agent for attenuating obesity, implying a potential mechanism for gut microbiota mediated the beneficial effect of Neo.}, }
@article {pmid32727864, year = {2020}, author = {Bhattacharjee, D and Seekatz, AM}, title = {Dilution as a Solution: Targeting Microbial Populations with a Simplified Dilution Strategy.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32727864}, issn = {2379-5042}, support = {K01 DK111794/DK/NIDDK NIH HHS/United States ; }, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {The gut microbiota is an integral part of maintaining resistance against infection by Clostridioides (Clostridium) difficile, a pathogen of increasing concern in both health care and community settings. The recent article by J. M. Auchtung, E. C. Preisner, J. Collins, A. I. Lerma, and R. A. Britton (mSphere 5:e00387-20, 2020, https://doi.org/10.1128/mSphere.00387-20) demonstrates an innovative approach to identify microbes that inhibit C. difficile by employing a dilution scheme to test different microbial mixtures in vitro and in vivo This type of approach can advance the identification and validation of specific microbes that elicit functions of interest for many conditions involving the microbiota, of which the complexity and variability can often complicate causality.}, }
@article {pmid32727857, year = {2020}, author = {Auchtung, JM and Preisner, EC and Collins, J and Lerma, AI and Britton, RA}, title = {Identification of Simplified Microbial Communities That Inhibit Clostridioides difficile Infection through Dilution/Extinction.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32727857}, issn = {2379-5042}, support = {R01 AI123278/AI/NIAID NIH HHS/United States ; R33 AI121522/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Animals ; Clostridioides difficile/*classification/*physiology ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Microbiological Techniques/*methods ; Middle Aged ; }, abstract = {The gastrointestinal microbiome plays an important role in limiting susceptibility to infection with Clostridioides difficile To better understand the ecology of bacteria important for C. difficile colonization resistance, we developed an experimental platform to simplify complex communities of fecal bacteria through dilution and rapidly screen for their ability to resist C. difficile colonization after challenge, as measured by >100-fold reduction in levels of C. difficile in challenged communities. We screened 76 simplified communities diluted from cultures of six fecal donors and identified 24 simplified communities that inhibited C. difficile colonization in vitro Sequencing revealed that simplified communities were composed of 19 to 67 operational taxonomic units (OTUs) and could be partitioned into four distinct community types. One simplified community could be further simplified from 56 to 28 OTUs through dilution and retain the ability to inhibit C. difficile We tested the efficacy of seven simplified communities in a humanized microbiota mouse model. We found that four communities were able to significantly reduce the severity of the initial C. difficile infection and limit susceptibility to disease relapse. Analysis of fecal microbiomes from treated mice demonstrated that simplified communities accelerated recovery of indigenous bacteria and led to stable engraftment of 19 to 22 OTUs from simplified communities. Overall, the insights gained through the identification and characterization of these simplified communities increase our understanding of the microbial dynamics of C. difficile infection and recovery.IMPORTANCEClostridioides difficile is the leading cause of antibiotic-associated diarrhea and a significant health care burden. Fecal microbiota transplantation is highly effective at treating recurrent C. difficile disease; however, uncertainties about the undefined composition of fecal material and potential long-term unintended health consequences remain. These concerns have motivated studies to identify new communities of microbes with a simpler composition that will be effective at treating disease. This work describes a platform for rapidly identifying and screening new simplified communities for efficacy in treating C. difficile infection. Four new simplified communities of microbes with potential for development of new therapies to treat C. difficile disease are identified. While this platform was developed and validated to model infection with C. difficile, the underlying principles described in the paper could be easily modified to develop therapeutics to treat other gastrointestinal diseases.}, }
@article {pmid32726437, year = {2020}, author = {Trivedi, R and Barve, K}, title = {Gut microbiome a promising target for management of respiratory diseases.}, journal = {The Biochemical journal}, volume = {477}, number = {14}, pages = {2679-2696}, doi = {10.1042/BCJ20200426}, pmid = {32726437}, issn = {1470-8728}, mesh = {Anti-Bacterial Agents/therapeutic use ; Asthma/etiology/microbiology ; Cystic Fibrosis/microbiology ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Lab-On-A-Chip Devices ; Lung Diseases/drug therapy/*etiology ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage/*therapeutic use ; Respiratory Tract Infections/drug therapy/*etiology ; Spray Drying ; Synbiotics/administration &amp; dosage ; }, abstract = {The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut-lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut-lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.}, }
@article {pmid32724908, year = {2020}, author = {Zukauckas, K and Vandiver, J and Biehle, L}, title = {It's time to rethink your approach to C diff infection.}, journal = {The Journal of family practice}, volume = {69}, number = {6}, pages = {293-300}, pmid = {32724908}, issn = {1533-7294}, mesh = {Abdominal Pain/etiology/physiopathology ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/drug effects/*pathogenicity ; Clostridium Infections/*drug therapy ; Cross Infection ; Diarrhea/etiology/physiopathology ; Female ; Humans ; Middle Aged ; Risk Factors ; Vancomycin/therapeutic use ; }, abstract = {Metronidazole is no longer the drug of choice for first-line therapy. And fecal microbiota transplantation has proven effective for certain patients.}, }
@article {pmid32723396, year = {2020}, author = {Shnaydman, I and Abdelhamid, MO and Kaufman, J and Lieberman, H and Ruiz, G}, title = {Colonic perforation due to inadvertent intraperitoneal LVAD driveline placement.}, journal = {Journal of cardiothoracic surgery}, volume = {15}, number = {1}, pages = {193}, pmid = {32723396}, issn = {1749-8090}, mesh = {Colectomy/methods ; Colon, Transverse/*injuries/surgery ; Heart Failure/*therapy ; Heart-Assist Devices/*adverse effects ; Humans ; Intestinal Perforation/*etiology/surgery ; Male ; Middle Aged ; Peritoneum ; *Postoperative Complications ; Reoperation ; }, abstract = {BACKGROUND: Left ventricular assist devices (LVAD) are placed for patients with advanced heart failure or cardiogenic shock as destination therapy or as a bridge to cardiac transplantation. Significant complications associated with LVAD placement include bleeding, infection, pump thrombosis, right heart failure, device malfunction and stroke. The case below illustrates inadvertent intraperitoneal driveline placement causing colonic perforation and the subsequent management.<br><br>CASE PRESENTATION: A 54&#x2009;year old male with a history of Wolff-Parkinson-White syndrome resulting in multiple readmissions for heart failure, ultimately required placement of a left ventricular assist device (LVAD). Several weeks later, he was found to have stool draining from the driveline site. The patient was taken to the operating room for limited exploration by the Cardiothoracic Surgery team and a bowel injury was identified and repaired. Three days after this repair, stool was once again leaking from the driveline site, requiring re-exploration by the Acute Care Surgery team. Intraoperatively, the prior repair was found to be leaking and multiple intra-abdominal abscesses were discovered. The transverse colon was resected and left in discontinuity. On a planned second look operation, the LVAD driveline was relocated to be extra-peritoneal and a colostomy was formed.<br><br>DISCUSSION AND CONCLUSION: This case demonstrates the importance of early recognition and involvement of an Acute Care Surgeon in the management of this complex problem. Appropriate treatment involves a complete exploration, source control, driveline relocation and possible fecal diversion. Although the incidence of this complication is low, it must be considered in the differential in a septic LVAD patient.}, }
@article {pmid32720604, year = {2020}, author = {Kushak, RI and Winter, HS}, title = {Gut Microbiota and Gender in Autism Spectrum Disorders.}, journal = {Current pediatric reviews}, volume = {16}, number = {4}, pages = {249-254}, doi = {10.2174/1573396316999200727123026}, pmid = {32720604}, issn = {1875-6336}, mesh = {Animals ; Anti-Bacterial Agents ; *Autism Spectrum Disorder/epidemiology ; Brain ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; *Probiotics/therapeutic use ; }, abstract = {Gender dimorphism in autism spectrum disorders (ASD) is well known; however, the reasons for gender differences in autism are poorly understood. There are several hypotheses that might explain male prevalence in ASD, including increased levels of androgens, "extreme male brain," and a combination of elevated levels of prenatal testosterone in conjunction with prenatal stress. In this comprehensive review, differences in the gut microbiome and metabolome in humans and animals are described to explain gender differences in individuals with ASD, effects on behavior and social interactions and the impact of antibiotics, probiotics and fecal transplants. The bidirectional relationship between sex hormones and intestinal microbiota could also be relevant. Such interactions have been described in autoimmune diseases, but thus far, are not implicated in ASD. Since intestinal microbiota may affect behavior, it is possible that the prevalence of ASD in boys may be associated with more significant changes in the intestinal microbiome than in affected girls.}, }
@article {pmid32718072, year = {2020}, author = {Wagner-Skacel, J and Dalkner, N and Moerkl, S and Kreuzer, K and Farzi, A and Lackner, S and Painold, A and Reininghaus, EZ and Butler, MI and Bengesser, S}, title = {Sleep and Microbiome in Psychiatric Diseases.}, journal = {Nutrients}, volume = {12}, number = {8}, pages = {}, pmid = {32718072}, issn = {2072-6643}, mesh = {Anorexia Nervosa ; Anxiety ; Bipolar Disorder ; Brain ; Circadian Rhythm ; Databases, Factual ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Gene Expression ; Humans ; *Mental Disorders ; *Microbiota ; Schizophrenia ; *Sleep ; }, abstract = {OBJECTIVES: Disturbances in the gut-brain barrier play an essential role in the development of mental disorders. There is considerable evidence showing that the gut microbiome not only affects digestive, metabolic and immune functions of the host but also regulates host sleep and mental states through the microbiota-gut-brain axis. The present review summarizes the role of the gut microbiome in the context of circadian rhythms, nutrition and sleep in psychiatric disorders.<br><br>METHODS: A PubMed search (studies published between April 2015-April 2020) was conducted with the keywords: "sleep, microbiome and psychiatry"; "sleep, microbiome and depression"; "sleep, microbiome and bipolar disorder", "sleep, microbiome and schizophrenia", "sleep, microbiome and anorexia nervosa", "sleep, microbiome and substance use disorder", "sleep, microbiome and anxiety"; "clock gene expression and microbiome", "clock gene expression and nutrition". Only studies investigating the relationship between sleep and microbiome in psychiatric patients were included in the review.<br><br>RESULTS: Search results yielded two cross-sectional studies analyzing sleep and gut microbiome in 154 individuals with bipolar disorder and one interventional study analyzing the effect of fecal microbiota transplantation in 17 individuals with irritable bowel syndrome on sleep. In patients with bipolar disorder, Faecalibacterium was significantly associated with improved sleep quality scores and a significant correlation between Lactobacillus counts and sleep.<br><br>CONCLUSION: Translational research on this important field is limited and further investigation of the bidirectional pathways on sleep and the gut microbiome in mood disorders is warranted.}, }
@article {pmid32717871, year = {2020}, author = {Chen, J and Vitetta, L}, title = {Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications.}, journal = {International journal of molecular sciences}, volume = {21}, number = {15}, pages = {}, pmid = {32717871}, issn = {1422-0067}, mesh = {Butyrates/metabolism ; *Dysbiosis/metabolism/microbiology/pathology ; *Gastrointestinal Microbiome ; Humans ; Inflammation/metabolism/microbiology/pathology ; *Intestinal Mucosa/metabolism/microbiology/pathology ; *Liver/metabolism/pathology ; *Non-alcoholic Fatty Liver Disease/metabolism/microbiology/pathology ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, G-Protein-Coupled/metabolism ; }, abstract = {Gut microbiota dysregulation plays a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) through its metabolites. Therefore, the restoration of the gut microbiota and supplementation with commensal bacterial metabolites can be of therapeutic benefit against the disease. In this review, we summarize the roles of various bacterial metabolites in the pathogenesis of NAFLD and their therapeutic implications. The gut microbiota dysregulation is a feature of NAFLD, and the signatures of gut microbiota are associated with the severity of the disease through altered bacterial metabolites. Disturbance of bile acid metabolism leads to underactivation of bile acid receptors FXR and TGR5, causal for decreased energy expenditure, increased lipogenesis, increased bile acid synthesis and increased macrophage activity. Decreased production of butyrate results in increased intestinal inflammation, increased gut permeability, endotoxemia and systemic inflammation. Dysregulation of amino acids and choline also contributes to lipid accumulation and to a chronic inflammatory status. In some NAFLD patients, overproduction of ethanol produced by bacteria is responsible for hepatic inflammation. Many approaches including probiotics, prebiotics, synbiotics, faecal microbiome transplantation and a fasting-mimicking diet have been applied to restore the gut microbiota for the improvement of NAFLD.}, }
@article {pmid32717434, year = {2020}, author = {Murthy, HS and Gharaibeh, RZ and Al-Mansour, Z and Kozlov, A and Trikha, G and Newsome, RC and Gauthier, J and Farhadfar, N and Wang, Y and Kelly, DL and Lybarger, J and Jobin, C and Wang, GP and Wingard, JR}, title = {Baseline Gut Microbiota Composition Is Associated with Major Infections Early after Hematopoietic Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {26}, number = {11}, pages = {2001-2010}, doi = {10.1016/j.bbmt.2020.07.023}, pmid = {32717434}, issn = {1523-6536}, mesh = {Bacteroidetes ; Feces ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Infection is a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Gut microbiota (GM) composition and metabolites provide colonization resistance against dominance of potential pathogens, and GM dysbiosis following HCT can be deleterious to immune reconstitution. Little is known about the composition, diversity, and evolution of GM communities in HCT patients and their association with subsequent febrile neutropenia (FN) and infection. Identification of markers before HCT that predict subsequent infection could be useful in developing individualized antimicrobial strategies. Fecal samples were collected prospectively from 33 HCT recipients at serial time points: baseline, post-conditioning regimen, neutropenia onset, FN onset (if present), and hematologic recovery. GM was assessed by 16S rRNA sequencing. FN and major infections (ie, bloodstream infection, typhlitis, invasive fungal infection, pneumonia, and Clostridium difficile enterocolitis) were identified. Significant shifts in GM composition and diversity were observed during HCT, with the largest alterations occurring after initiation of antibiotics. Loss of diversity persisted without a return to baseline at hematologic recovery. GM in patients with FN was enriched in Mogibacterium, Bacteroides fragilis, and Parabacteroides distasonis, whereas increased abundance of Prevotella, Ruminococcus, Dorea, Blautia, and Collinsella was observed in patients without fever. A baseline protective GM profile (BPGMP) was predictive of protection from major infection. The BPGMP was associated with subsequent major infections with 77% accuracy and an area under the curve of 79%, with sensitivity, specificity, and positive and negative predictive values of 0.71, 0.91, 0.77, and 0.87, respectively. Our data show that large shifts in GM composition occur early after HCT, and differences in baseline GM composition are associated with the development of subsequent major infections.}, }
@article {pmid32713818, year = {2020}, author = {Dobies, A and Renke, M and Kubanek, A and Rzyska, P and Wołyniec, W and Páleníček, L and Król, E and Lizakowski, S and Rutkowski, P and Tylicki, L and Dębska-Ślizień, A}, title = {Gastrointestinal Pathologies in Patients After Successful Renal Transplantation.}, journal = {Transplantation proceedings}, volume = {52}, number = {8}, pages = {2412-2416}, doi = {10.1016/j.transproceed.2020.02.121}, pmid = {32713818}, issn = {1873-2623}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Gastrointestinal Diseases/*epidemiology/etiology ; Humans ; Kidney Failure, Chronic/*surgery ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Poland/epidemiology ; Postoperative Complications/*epidemiology/etiology ; Prevalence ; Renal Dialysis ; Risk Factors ; }, abstract = {BACKGROUND: Kidney transplantation (KT) is the most desired and cost-effective modality of renal replacement therapy for patients with chronic kidney failure. KT protects the patient from complications that may develop during chronic dialysis. Unfortunately, evidence also suggests that KT patients are more prone to developing cancer than healthy persons. Many complications after renal transplantation can be prevented if they are detected early. The aim of this study was to evaluate the prevalence of gastrointestinal pathologies in patients after KT.<br><br>METHODS: Adult patients after KT who are under the care of the Outpatient Department of Nephrology at the Medical University of Gda&#x144;sk, Poland, received alarm symptom questionnaires and referral for testing for the presence of fecal occult blood. Then, in 58 selected patients (36 men and 22 women), endoscopic examination was performed. Mean age was 57.34 &#xb1; 10.1 (range, 35-83) years.<br><br>RESULTS: Out of 940 patients after KT, resting under supervision of the Outpatient Department, 208 patients completed the questionnaire and 118 gave a stool sample for testing: 40 results were positive. After analyzing the questionnaires and stool results, 100 patients quali&#xfb01;ed for further investigation. The endoscopic examination had been performed so far in 58 patients and revealed gastritis and/or duodenitis in 49 patients, diverticular colon disease in 26, esophagitis in 8, colon polyps in 16, stomach polyps in 4, in&#xfb02;ammatory bowel disease in 12, and cancers in&#xa0;3.<br><br>CONCLUSIONS: The preliminary results indicate that patients after KT have signi&#xfb01;cant risk of gastrointestinal pathologies and require detailed diagnostic endoscopy.}, }
@article {pmid32713786, year = {2021}, author = {Chiu, CH and Tsai, MC and Cheng, HT and Le, PH and Kuo, CJ and Chiu, CT}, title = {Fecal microbiota transplantation and donor screening for Clostridioides difficile infection during COVID-19 pandemic.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {120}, number = {2}, pages = {791-793}, pmid = {32713786}, issn = {0929-6646}, mesh = {*COVID-19 ; Clostridioides difficile/*isolation &amp; purification ; *Donor Selection ; *Fecal Microbiota Transplantation ; Humans ; Pandemics ; }, }
@article {pmid32712721, year = {2021}, author = {Reyes-Castillo, Z and Valdés-Miramontes, E and Llamas-Covarrubias, M and Muñoz-Valle, JF}, title = {Troublesome friends within us: the role of gut microbiota on rheumatoid arthritis etiopathogenesis and its clinical and therapeutic relevance.}, journal = {Clinical and experimental medicine}, volume = {21}, number = {1}, pages = {1-13}, pmid = {32712721}, issn = {1591-9528}, mesh = {Animals ; Arthritis, Rheumatoid/etiology/*pathology ; Dysbiosis/*complications ; *Gastrointestinal Microbiome ; Humans ; Inflammation/*complications ; }, abstract = {The role of gut microbiota on immune regulation and the development of autoimmune diseases such as rheumatoid arthritis (RA) is an emerging research topic. Multiple studies have demonstrated alterations on gut microbiota composition and/or function (referred to as dysbiosis) both in early and established RA patients. Still, research delineating the molecular mechanisms by which gut microorganisms induce the loss of immune tolerance or contribute to disease progression is scarce. Available data indicate that gut microbiota alterations are involved in RA autoimmune response by several mechanisms including the post-translational modification of host proteins, molecular mimicry between bacterial and host epitopes, activation of immune system and polarization toward inflammatory phenotypes, as well as induction of intestinal permeability. Therefore, in this review we analyze recent clinical and molecular evidence linking gut microbiota with the etiopathogenesis of RA. The potential of the gut microbiota as a diagnostic or severity biomarker is discussed, as well as the opportunity areas for the development of complementary therapeutic strategies based on the modulation of gut microbiota in the rheumatic patient.}, }
@article {pmid32711581, year = {2020}, author = {Zhang, P and Liu, J and Xiong, B and Zhang, C and Kang, B and Gao, Y and Li, Z and Ge, W and Cheng, S and Hao, Y and Shen, W and Yu, S and Chen, L and Tang, X and Zhao, Y and Zhang, H}, title = {Microbiota from alginate oligosaccharide-dosed mice successfully mitigated small intestinal mucositis.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {112}, pmid = {32711581}, issn = {2049-2618}, mesh = {Alginates/*pharmacology ; Animals ; Busulfan/adverse effects ; *Fecal Microbiota Transplantation ; Intestine, Small/drug effects/*microbiology/*pathology ; Male ; Mice ; Mice, Inbred ICR ; Microbiota/*drug effects ; Mucositis/chemically induced/*microbiology/*therapy ; Oligosaccharides/*pharmacology ; }, abstract = {BACKGROUND: The increasing incidence of cancer and intestinal mucositis induced by chemotherapeutics are causing worldwide concern. Many approaches such as fecal microbiota transplantation (FMT) have been used to minimize mucositis. However, it is still unknown whether FMT from a donor with beneficial gut microbiota results in more effective intestinal function in the recipient. Recently, we found that alginate oligosaccharides (AOS) benefit murine gut microbiota through increasing "beneficial" microbes to rescue busulfan induced mucositis.<br><br>RESULTS: In the current investigation, FMT from AOS-dosed mice improved small intestine function over FMT from control mice through the recovery of gene expression and an increase in the levels of cell junction proteins. FMT from AOS-dosed mice showed superior benefits over FMT from control mice on recipient gut microbiotas through an increase in "beneficial" microbes such as Leuconostocaceae and recovery in blood metabolome. Furthermore, the correlation of gut microbiota and blood metabolites suggested that the "beneficial" microbe Lactobacillales helped with the recovery of blood metabolites, while the "harmful" microbe Mycoplasmatales did not.<br><br>CONCLUSION: The data confirm our hypothesis that FMT from a donor with superior microbes leads to a more profound recovery of small intestinal function. We propose that gut microbiota from naturally produced AOS-treated donor may be used to prevent small intestinal mucositis induced by chemotherapeutics or other factors in recipients. Video Abstract.}, }
@article {pmid32710226, year = {2020}, author = {Mohan, N and Deswal, S}, title = {Corona Virus Disease (COVID-19) Fecal-oral transmission: Is it a potential risk for Indians?.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {39}, number = {3}, pages = {305-306}, pmid = {32710226}, issn = {0975-0711}, mesh = {Betacoronavirus/*isolation &amp; purification ; COVID-19 ; COVID-19 Testing ; Clinical Laboratory Techniques/*methods ; *Coronavirus Infections/diagnosis/epidemiology/physiopathology/prevention &amp; control/transmission ; Disease Transmission, Infectious/*prevention &amp; control ; Feces/*virology ; *Gastrointestinal Diseases/diagnosis/etiology/physiopathology ; Gastrointestinal Tract/virology ; Humans ; India/epidemiology ; *Pandemics/prevention &amp; control ; *Pneumonia, Viral/epidemiology/physiopathology/prevention &amp; control/transmission ; Public Health ; SARS-CoV-2 ; Universal Precautions/methods ; }, }
@article {pmid32702186, year = {2020}, author = {Zhao, D and Dai, W and Tao, H and Zhuang, W and Qu, M and Chang, YN}, title = {Polysaccharide isolated from Auricularia auricular-judae (Bull.) prevents dextran sulfate sodium-induced colitis in mice through modulating the composition of the gut microbiota.}, journal = {Journal of food science}, volume = {85}, number = {9}, pages = {2943-2951}, doi = {10.1111/1750-3841.15319}, pmid = {32702186}, issn = {1750-3841}, mesh = {Animals ; Basidiomycota/*chemistry ; Colitis, Ulcerative/chemically induced/*microbiology/*prevention &amp; control ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Mice ; Mice, Inbred C57BL ; Plant Extracts/*administration &amp; dosage/isolation &amp; purification ; Polysaccharides/*administration &amp; dosage/isolation &amp; purification ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic intestinal disease, which was commonly found in westerners whereas is increasingly prevalent in Asia because of the changing eating habits. In previous research, we found that a water-soluble polysaccharide isolated from Auricularia auricular-judae (Bull.)-a kind of edible mushroom (Aap)-is composed of β-1,3 glycosidic bonds, which is regarded as therapeutic or protective substance in enteritis. We therefore aimed to find the preventing effect of Aap on IBD. Here, we reported that pre-administration of Aap not only ameliorated weight loss, colon damage, and mucosal inflammation in colitis mice, but also prevented the damage of intestinal barrier by reducing the D-lactic acid and diamine oxidase level in plasma. Through high-throughput sequencing, we found that Aap changed gut microbiota composition. Furthermore, the preventing effect was transmissible via horizontal feces transfer from Aap-treated mice to normal mice. Our results indicated that oral administration of Aap is a promising protective substance of IBD. PRACTICAL APPLICATION: Our study proved that Auricularia auricula polysaccharide had substantial preventing effect on DSS-induced colitis in mice. This research might lay the theoretical foundation and technical support for the development of related functional foods. People could also enhance their gut immunity by eating Auricularia auricular in their daily life. Auricularia auricular as a highly nutritious agricultural product showed the broad significance in nutrition and food function.}, }
@article {pmid32701590, year = {2020}, author = {}, title = {Nanjing consensus on methodology of washed microbiota transplantation.}, journal = {Chinese medical journal}, volume = {133}, number = {19}, pages = {2330-2332}, pmid = {32701590}, issn = {2542-5641}, mesh = {Consensus ; Feces ; *Microbiota ; }, }
@article {pmid32701563, year = {2021}, author = {Tariq, R and Saha, S and Solanky, D and Pardi, DS and Khanna, S}, title = {Predictors and Management of Failed Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {55}, number = {6}, pages = {542-547}, doi = {10.1097/MCG.0000000000001398}, pmid = {32701563}, issn = {1539-2031}, mesh = {Case-Control Studies ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND AND GOALS: Clostridioides difficile infection (CDI) recurs in 10% to 15% after fecal microbiota transplantation (FMT). We identify predictors, and describe management and outcome of patients with recurrent CDI after FMT in a predominantly outpatient cohort.<br><br>METHODS: A nested case-control study of patients undergoing FMT for recurrent CDI from August 2012 to January 2017 was performed. FMT failure was defined as recurrent diarrhea with positive C. difficile stool test during follow-up (&#x2265;2&#x2009;mo). Controls (patients without FMT failures) were matched to cases 1:1 for sex and timing of FMT&#xb1;1 month.<br><br>RESULTS: Overall, 522 patients underwent FMT; 70 [13.4%; median age 53.8 years (range, 18 to 89&#x2009;y), 54.3% females] recurred within a median 5.6 months (range, 0.2 to 34.9&#x2009;mo). Number of prior CDI episodes, prior CDI treatment, and prior CDI-related hospitalizations were similar in cases and controls. Systemic antibiotics after FMT (54.3% vs. 21.4%, P<0.0001), inflammatory bowel disease (IBD) (34.3% vs. 15.7%, P=0.01), pseudomembranes at FMT (4.3% vs. 0%, P=0.03), and poor bowel preparation (68.5% vs. 31.4%, P=0.01) were associated with FMT failure. On multivariate analysis, IBD [odds ratio (OR) 4.34; 95% confidence interval (CI), 1.24-15.15], systemic antibiotics (OR 7.39; 95% CI, 3.02-18.07), and poor bowel preparation (OR 3.84; 95% CI, 1.59-9.28) predicted FMT failure with an area under the curve of 0.78. Among FMT failures, 37 (52.8%) were managed with antibiotics, 32 (45.7%) with repeat FMT after antibiotics and 1 with colectomy.<br><br>CONCLUSIONS: Use of systemic antibiotics, IBD, and poor bowel preparation predict FMT failure. Patients with FMT failure can be managed with antibiotics and/or repeat FMT.}, }
@article {pmid32699120, year = {2020}, author = {Rao, K and Seekatz, A and Bassis, C and Sun, Y and Mantlo, E and Bachman, MA}, title = {Enterobacterales Infection after Intestinal Dominance in Hospitalized Patients.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32699120}, issn = {2379-5042}, support = {R01 AI125307/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Case-Control Studies ; Colony Count, Microbial ; Cross Infection ; Enterobacteriaceae/*classification/*pathogenicity ; Enterobacteriaceae Infections/*etiology/*microbiology ; Female ; Hospitalization/*statistics &amp; numerical data ; Humans ; Intestines/*microbiology ; Male ; Middle Aged ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics ; Rectum/microbiology ; }, abstract = {The Enterobacterales order of Gram-negative bacteria includes the common nosocomial pathogens Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, and Enterobacter species. Intestinal domination by some colonizing bacterial taxa is associated with subsequent infection, but 16S rRNA gene sequencing is too costly and slow to be used in a clinical setting. The objectives of this study were to develop a PCR-based assay that can measure Enterobacterales density, validate it against 16S rRNA gene sequencing, and measure the association between Enterobacterales dominance and subsequent infection. Two quantitative PCR (qPCR) assays that were developed to quantify the absolute and relative abundance of Enterobacterales had good correlation with 16S rRNA sequence analysis (P < 0.0001). Using both PCR assays and 16S sequencing, a matched case-control study was performed comparing rectal swabs from hospitalized patients who later developed bloodstream, urinary tract, or respiratory Enterobacterales infections (n = 95) to swabs from patients who remained uninfected (n = 189). Enterobacterales abundance measured by sequencing was high in both cases and controls (means, 31.1% and 27.5%, respectively; P = 0.322). We observed an increased risk of infection that depended on both the absolute and relative abundance of Enterobacterales as measured by qPCR assay A (P = 0.012). After adjustment for albumin levels, central venous catheter presence, and use of cephalosporins at the time of swab collection, this association still approached significance (P = 0.061). These results demonstrate that using qPCR to measure intestinal colonization dominance is feasible, indicate that hospitalized patients have high levels of Enterobacterales colonization, and suggest that both relative and absolute abundance may be associated with subsequent infection.IMPORTANCE Increasing antibiotic resistance has resulted in infections that are life-threatening and difficult to treat. Interventions that prevent these infections, particularly without using antibiotics, could save lives. Intestinal colonization by pathogens, including vancomycin-resistant Enterococcus and carbapenem-resistant Enterobacteriaceae (part of the order Enterobacterales) is associated with subsequent infection, and increased colonization density is associated with increased infection risk. Therefore, colonization offers a window of opportunity for infection prevention if (i) there are rapid and inexpensive assays to detect colonization, (ii) there are safe and effective interventions, and (iii) the risk of infection outweighs the risk of the treatment. Fecal transplants are proof of principle that manipulating the microbiome can reduce such colonization and prevent infections. This study demonstrates the feasibility of implementing rapid and inexpensive assays to quantify colonization and measures the strength of association between Enterobacterales dominance and subsequent infection. The approach described here could be a valuable tool in the prevention of antibiotic-resistant infections.}, }
@article {pmid32697259, year = {2020}, author = {Jing, N and Liu, X and Jin, M and Yang, X and Hu, X and Li, C and Zhao, K}, title = {Fubrick tea attenuates high-fat diet induced fat deposition and metabolic disorder by regulating gut microbiota and caffeine metabolism.}, journal = {Food &amp; function}, volume = {11}, number = {8}, pages = {6971-6986}, doi = {10.1039/d0fo01282c}, pmid = {32697259}, issn = {2042-650X}, mesh = {Animals ; Anti-Obesity Agents/*pharmacology ; Caffeine/metabolism ; Diet, High-Fat/adverse effects ; *Dietary Supplements ; Disease Models, Animal ; Dyslipidemias/complications/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects ; Glucose Intolerance/complications/therapy ; Intra-Abdominal Fat/drug effects ; Lipid Metabolism/drug effects ; Male ; Metabolic Diseases/complications/metabolism/*therapy ; Mice ; Mice, Inbred C57BL ; Obesity/etiology/*prevention &amp; control ; Plant Extracts/*pharmacology ; *Tea ; Weight Gain/drug effects ; }, abstract = {Fubrick tea aqueous extract (FTEs) has been reported to improve lipid metabolism and gut microbiota communities in mice and humans. However, it is still unclear how FTEs prevents obesity through gut microbiota, and whether some other regulatory mechanisms are involved in the process. Here, we found that FTEs supplementation effectively alleviated the body weight gain, visceral fat accumulation, dyslipidemia, and impaired glucose tolerance induced by a high-fat diet (HFD), and fecal microbiota transplantation (FMT) from FTEs-treated mice showed similar protective effects as FTEs supplementation in mice fed with a HFD. The results confirmed that gut microbiota played key roles in attenuating HFD-induced fat deposition and metabolic disorder. In particular, FTEs reversed HFD-induced gut microbiota dysbiosis via increasing the relative abundances of Bacteroides, Adlercreutzia, Alistipes, Parabacteroides, and norank_f_Lachnospiraceae, and reducing that of Staphylococcus. Interestingly, FTEs could still alleviate HFD-induced lipid accumulation in mice treated with antibiotics, which had increased relative abundances of Bacteroidetes, Bacteroides, and Bacteroides_uniformis sp. In addition, supplementation with FTEs also modified the serum metabolome, especially the "caffeine metabolism" pathway. Furthermore, FTEs supplementation increased the concentrations of caffeine, theophylline, and theobromine in serum, which were positively correlated with an abundance of norank_f_Lachnospiraceae. Overall, FTEs exerts beneficial effects against obesity induced by HFD, and the underlying mechanism is partially related to the reprogramming of intestinal microbiota, while the metabolism of caffeine in FTEs also played an important role in the process. This study provides a theoretical basis for the further study of the anti-obesity effects of FTEs and the consideration of gut microbiota as a potential target for the treatment of obesity induced by a HFD.}, }
@article {pmid32694178, year = {2021}, author = {Zhang, X and Coker, OO and Chu, ES and Fu, K and Lau, HCH and Wang, YX and Chan, AWH and Wei, H and Yang, X and Sung, JJY and Yu, J}, title = {Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites.}, journal = {Gut}, volume = {70}, number = {4}, pages = {761-774}, pmid = {32694178}, issn = {1468-3288}, mesh = {Animals ; Atorvastatin/*pharmacology ; Carcinoma, Hepatocellular/etiology/*prevention &amp; control ; Case-Control Studies ; *Cholesterol, Dietary ; Disease Progression ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Liver Neoplasms/etiology/*prevention &amp; control ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/complications/*prevention &amp; control ; }, abstract = {OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is an increasing healthcare burden worldwide. We examined the role of dietary cholesterol in driving NAFLD-HCC through modulating gut microbiota and its metabolites.<br><br>DESIGN: High-fat/high-cholesterol (HFHC), high-fat/low-cholesterol or normal chow diet was fed to C57BL/6 male littermates for 14 months. Cholesterol-lowering drug atorvastatin was administered to HFHC-fed mice. Germ-free mice were transplanted with stools from mice fed different diets to determine the direct role of cholesterol modulated-microbiota in NAFLD-HCC. Gut microbiota was analysed by 16S rRNA sequencing and serum metabolites by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. Faecal microbial compositions were examined in 59 hypercholesterolemia patients and 39 healthy controls.<br><br>RESULTS: High dietary cholesterol led to the sequential progression of steatosis, steatohepatitis, fibrosis and eventually HCC in mice, concomitant with insulin resistance. Cholesterol-induced NAFLD-HCC formation was associated with gut microbiota dysbiosis. The microbiota composition clustered distinctly along stages of steatosis, steatohepatitis and HCC. Mucispirillum, Desulfovibrio, Anaerotruncus and Desulfovibrionaceae increased sequentially; while Bifidobacterium and Bacteroides were depleted in HFHC-fed mice, which was corroborated in human hypercholesteremia patients. Dietary cholesterol induced gut bacterial metabolites alteration including increased taurocholic acid and decreased 3-indolepropionic acid. Germ-free mice gavaged with stools from mice fed HFHC manifested hepatic lipid accumulation, inflammation and cell proliferation. Moreover, atorvastatin restored cholesterol-induced gut microbiota dysbiosis and completely prevented NAFLD-HCC development.<br><br>CONCLUSIONS: Dietary cholesterol drives NAFLD-HCC formation by inducing alteration of gut microbiota and metabolites in mice. Cholesterol inhibitory therapy and gut microbiota manipulation may be effective strategies for NAFLD-HCC prevention.}, }
@article {pmid32691508, year = {2020}, author = {Liu, XJ and Wu, LH and Xie, WR and He, XX}, title = {Faecal microbiota transplantation simultaneously ameliorated patient's essential tremor and irritable bowel syndrome.}, journal = {Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society}, volume = {20}, number = {5}, pages = {796-798}, pmid = {32691508}, issn = {1479-8301}, mesh = {*Essential Tremor ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid32690735, year = {2020}, author = {Jiménez-Jorge, S and Labrador-Herrera, G and Rosso-Fernández, CM and Rodríguez-Torres, N and Pachón-Ibáñez, ME and Smani, Y and Márquez-Malaver, FJ and Limón Ramos, C and Solano, C and Vázquez-López, L and Kwon, M and Mora Barrios, JM and Aguilar-Guisado, M and Espigado, I and , }, title = {Assessing the impact on intestinal microbiome and clinical outcomes of antibiotherapy optimisation strategies in haematopoietic stem cell transplant recipients: study protocol for the prospective multicentre OptimBioma study.}, journal = {BMJ open}, volume = {10}, number = {7}, pages = {e034570}, pmid = {32690735}, issn = {2044-6055}, mesh = {*Antibiotic Prophylaxis ; *Antimicrobial Stewardship ; Case-Control Studies ; Feces/microbiology ; *Gastrointestinal Microbiome ; Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation ; Humans ; Longitudinal Studies ; Multicenter Studies as Topic ; *Observational Studies as Topic ; Prospective Studies ; Research Design ; *Transplant Recipients ; }, abstract = {INTRODUCTION: Haematopoietic stem cell transplantation (HSCT) is a life-saving treatment for a number of haematological diseases. Graft versus host disease (GVHD) is its main complication and hampers survival. There is strong evidence that intestinal microbiota diversity of the recipient may increase the risk of GVHD worsening survival. Antibiotic regimens used during the early phase of the transplant may influence clinical outcomes by reducing intestinal microbiota diversity. Present guidelines of European Conference on Infections in Leukaemia exhort to optimising antibiotic use in haematological patients including HSCT recipients. The present study aims to investigate if, in HSCT recipients, the optimisation of antibacterial use may preserve intestinal microbiota composition reducing the incidence and severity of acute GVHD and improving relevant clinical outcomes.<br><br>METHODS AND ANALYSIS: This is a prospective longitudinal observational study of two cohorts of HSCT recipients: (1) the intervention cohort includes patients treated in centres in which a predefined strategy of antibiotherapy optimisation is implemented, with the objective of optimising and reducing antibiotic administration according to clinical criteria and (2) the control cohort includes patients treated in centres in which a classic permissive strategy of antibiotic prophylaxis and treatment is used. Adult patient receiving a first HSCT as a treatment for any haematological condition are included. Clinical variables are prospectively recorded and up to five faecal samples are collected for microbiota characterisation at prestablished peritransplant time points. Patients are followed since the preconditioning phase throughout 1-year post-transplant and four follow-up visits are scheduled. Faecal microbiota composition and diversity will be compared between both cohorts along with acute GVHD incidence and severity, severe infections rate, mortality and overall and disease-free survival.<br><br>ETHICS AND DISSEMINATION: The study was approved between 2017 and 2018 by the Ethical Committees of participant centres. Study results will be disseminated through peer-reviewed journals and national and international scientific conferences.<br><br>TRIAL REGISTRATION NUMBER: NCT03727113.}, }
@article {pmid32690139, year = {2020}, author = {Halsey, T and Ologun, G and Wargo, J and Jenq, RR}, title = {Uncovering the role of the gut microbiota in immune checkpoint blockade therapy: A mini-review.}, journal = {Seminars in hematology}, volume = {57}, number = {1}, pages = {13-18}, pmid = {32690139}, issn = {1532-8686}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Gastrointestinal Microbiome/*immunology ; Humans ; Immune Checkpoint Inhibitors/pharmacology/*therapeutic use ; Mice ; }, abstract = {In recent years, the microbiota has been implicated as a key factor associated with both response and toxicity from immune checkpoint blockade therapy. Numerous studies have been published that specifically highlight the importance of the microbiome as a distinct influencer of anti-PD-1/PD-L1 and anti-CTLA-4 activity in cancer patients, but a full understanding of mechanisms behind these interactions has yet to be achieved. With greater insight into how the microbiome can modulate immune checkpoint blockade comes the potential to target the microbiome to improve response rates and minimize toxicities. This mini-review looks at noteworthy studies that have explored the relationship between the microbiome and immune checkpoint blockade response and toxicity in both preclinical and clinical studies, with an emphasis on current hypotheses regarding mechanisms of action and potential microbiome-targeted therapeutic strategies under development.}, }
@article {pmid32690030, year = {2020}, author = {Stadlbauer, V and Engertsberger, L and Komarova, I and Feldbacher, N and Leber, B and Pichler, G and Fink, N and Scarpatetti, M and Schippinger, W and Schmidt, R and Horvath, A}, title = {Dysbiosis, gut barrier dysfunction and inflammation in dementia: a pilot study.}, journal = {BMC geriatrics}, volume = {20}, number = {1}, pages = {248}, pmid = {32690030}, issn = {1471-2318}, support = {Center for Biomarker Research in Medicine//&#xd6;sterreichische Forschungsf&#xf6;rderungsgesellschaft/International ; }, mesh = {Bacteria ; *Dementia ; Dysbiosis ; Feces ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Dementia is an increasing public health threat worldwide. The pathogenesis of dementia has not been fully elucidated yet. Inflammatory processes are hypothesized to play an important role as a driver for cognitive decline but the origin of inflammation is not clear. We hypothesize that disturbances in gut microbiome composition, gut barrier dysfunction, bacterial translocation and resulting inflammation are associated with cognitive dysfunction in dementia.<br><br>METHODS: To test this hypothesis, a cohort of 23 patients with dementia and 18 age and sex matched controls without cognitive impairments were studied. Gut microbiome composition, gut barrier dysfunction, bacterial translocation and inflammation were assessed from stool and serum samples. Malnutrition was assessed by Mini Nutritional Assessment Short Form (MNA-SF), detailed information on drug use was collected. Microbiome composition was assessed by 16S rRNA sequencing, QIIME 2 and Calypso 7.14 tools.<br><br>RESULTS: Dementia was associated with dysbiosis characterized by differences in beta diversity and changes in taxonomic composition. Gut permeability was increased as evidenced by increased serum diamine oxidase (DAO) levels and systemic inflammation was confirmed by increased soluble cluster of differentiation 14 levels (sCD14). BMI and statin use had the strongest impact on microbiome composition.<br><br>CONCLUSION: Dementia is associated with changes in gut microbiome composition and increased biomarkers of gut permeability and inflammation. Lachnospiraceae NK4A136 group as potential butyrate producer was reduced in dementia. Malnutrition and drug intake were factors, that impact on microbiome composition. Increasing butyrate producing bacteria and targeting malnutrition may be promising therapeutic targets in dementia.<br><br>TRIAL REGISTRATION: NCT03167983 .}, }
@article {pmid32687975, year = {2020}, author = {Siddiqui, MT and Cresci, GAM}, title = {Microbiota reprogramming for treatment of alcohol-related liver disease.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {226}, number = {}, pages = {26-38}, pmid = {32687975}, issn = {1878-1810}, support = {R00 AA023266/AA/NIAAA NIH HHS/United States ; T32 DK083251/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Liver Diseases, Alcoholic/physiopathology/*therapy ; Probiotics ; }, abstract = {In the past decade knowledge has expanded regarding the importance of the gut microbiota in maintaining intestinal homeostasis and overall health. During this same time, we have also gained appreciation for the role of the gut-liver axis in the development of liver diseases. Alcohol overconsumption is one of the leading causes of liver failure globally. However, not all people with alcohol use disorder progress to advanced stages of liver disease. With advances in technology to investigate the gut microbiome and metabolome, we are now beginning to delineate alcohol's effects on the gut microbiome in relation to liver disease. This review presents our current understanding on the role of the gut microbiota during alcohol exposure, and various therapeutic attempts that have been made to reprogram the gut microbiota with the goal of alleviating alcoholic-related liver disease.}, }
@article {pmid32686598, year = {2020}, author = {Zhu, Z and Huang, J and Li, X and Xing, J and Chen, Q and Liu, R and Hua, F and Qiu, Z and Song, Y and Bai, C and Mo, YY and Zhang, Z}, title = {Gut microbiota regulate tumor metastasis via circRNA/miRNA networks.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1788891}, pmid = {32686598}, issn = {1949-0984}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects ; Dysbiosis/chemically induced/microbiology ; Epithelial-Mesenchymal Transition/genetics ; Gastrointestinal Microbiome/genetics/*physiology ; Gene Expression Regulation, Neoplastic/genetics ; Interleukin-11/genetics/metabolism ; Mice ; MicroRNAs/*metabolism ; Neoplasm Metastasis/genetics/*pathology ; Neoplastic Stem Cells/metabolism/pathology ; RNA, Circular/*metabolism ; SOX9 Transcription Factor/genetics/metabolism ; *Signal Transduction ; }, abstract = {BACKGROUND: Increasing evidence indicates that gut microbiota plays an important role in cancer progression. However, the underlying mechanism remains largely unknown. Here, we report that broad-spectrum antibiotics (ABX) treatment leads to enhanced metastasis by the alteration of gut microbiome composition.<br><br>METHODS: Cancer LLC and B16-F10 cell metastasis mouse models, and microarray/RNA sequencing analysis were used to reveal the regulatory functions of microbiota-mediated circular RNA (circRNA)/microRNA (miRNA) networks that may contribute to cancer metastasis.<br><br>RESULTS: The specific pathogen-free (SPF) mice with ABX treatment demonstrated enhanced lung metastasis. Fecal microbiota transplantation (FMT) from SPF mice or Bifidobacterium into germ-free mice significantly suppressed lung metastasis. Mechanistically, gut microbiota impacts circRNA expression to regulate levels of corresponding miRNAs. Specifically, such modulations of gut microbiota inhibit mmu_circ_0000730 expression in an IL-11-dependent manner. Bioinformatics analysis combined with luciferase reporter assays revealed reciprocal repression between mmu_circ_0000730 and mmu-miR-466i-3p. We further showed that both mmu-miR-466i-3p and mmu-miR-466&#xa0;f-3p suppresses a number of genes involved in epithelial-mesenchymal transition (EMT) and stemness of cancer stem cells such as SOX9.<br><br>CONCLUSIONS: These results provide evidence of a previously unrecognized regulatory role of non-coding RNAs in microbiota-mediated cancer metastasis, and thus, the microbiome may serve as a therapeutic target.}, }
@article {pmid32685087, year = {2020}, author = {Wei, Z and Shen, P and Cheng, P and Lu, Y and Wang, A and Sun, Z}, title = {Gut Bacteria Selectively Altered by Sennoside A Alleviate Type 2 Diabetes and Obesity Traits.}, journal = {Oxidative medicine and cellular longevity}, volume = {2020}, number = {}, pages = {2375676}, pmid = {32685087}, issn = {1942-0994}, mesh = {Animals ; Diabetes Mellitus, Type 2/*drug therapy ; Disease Models, Animal ; Gastrointestinal Microbiome/*drug effects ; Humans ; Laxatives/pharmacology/*therapeutic use ; Male ; Mice ; Obesity/*drug therapy ; Sennosides/pharmacology/*therapeutic use ; }, abstract = {Accumulating evidences implicate that gut microbiota play an important role in the onset and prolongation of fat inflammation and diabetes. Sennoside A, the main active ingredient of Rhizoma Rhei (rhubarb), is widely used for constipation as a kind of anthranoid laxative (e.g., senna). Here, we put forward the hypothesis that the structural alteration of gut microbiota in obesity mice may be involved in the pathogenesis of type 2 diabetes (T2D) which may be ameliorated by Sennoside A. We investigated the appearance of obesity, insulin resistance, host inflammation, and leaky gut phenotype with or without Sennoside A in db/db mice. Horizontal fecal microbiota transplantation (FMT) was used to confirm the critical roles of gut microbiota in the amelioration of the indices in T2D mice after Sennoside A treatment. As a result, we found that Sennoside A administration markedly improved the indices in T2D mice and obesity-related traits including blood glucose level, body weight, lipid metabolism disorder, and insulin resistance. The gut microbiota changed quickly during the onset of T2D in db/db mice, which confirmed the hypothesis that gut microbiota was involved in the pathogenesis of T2D. Sennoside A altered gut microbial composition which might mediate the antiobesogenic effects in T2D remission. Sennoside A also reduced inflammation and increased tight junction proteins in the ileum in gene-deficient mice via gut microbiota alteration. FMT lowered the blood glucose level and improved insulin resistance, corroborating that Sennoside A perhaps exerted its antiobesogenic effects through gut microbiota alteration. Chemical Compounds Studied in This Article. Compounds studied in this article include Sennoside A (PubChem CID: 73111) and metformin hydrochloride (PubChem CID: 14219).}, }
@article {pmid32684346, year = {2020}, author = {Martínez-González, AE and Andreo-Martínez, P}, title = {Prebiotics, probiotics and fecal microbiota transplantation in autism: A systematic review.}, journal = {Revista de psiquiatria y salud mental}, volume = {13}, number = {3}, pages = {150-164}, doi = {10.1016/j.rpsm.2020.06.002}, pmid = {32684346}, issn = {2173-5050}, abstract = {In recent years, there has been an increase in studies of the implications of the gut microbiota (GM) in children with autism spectrum disorder (ASD). There is a hypothesis which propose a relationship between the emotional state and the abundance of intestinal microbes through the so-called microbiota-intestine-brain axis. In this sense, dysbiotic GM could be a contributing factor to the appearance of ASD. This systematic review article analyzes the results of the intervention using prebiotics (carrot powder, vitamin A, partially hydrolyzed guar gum, galactooligosaccharides, etc.), probiotics (mainly: Lactobacillus, Bifidobacterium, etc.) and transplantation of fecal microbiota in ASD children. In conclusion, the results of the initial studies suggest changes in ASD symptoms, gastro-intestinal symptoms and GM composition after the interventions. However, the results should be taken with caution because there are very few studies that analyze the efficacy of long-term treatments and the different combinations of them.}, }
@article {pmid32682948, year = {2020}, author = {Tanaka, JS and Young, RR and Heston, SM and Jenkins, K and Spees, LP and Sung, AD and Corbet, K and Thompson, JC and Bohannon, L and Martin, PL and Stokhuyzen, A and Vinesett, R and Ward, DV and Bhattarai, SK and Bucci, V and Arshad, M and Seed, PC and Kelly, MS}, title = {Anaerobic Antibiotics and the Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {26}, number = {11}, pages = {2053-2060}, pmid = {32682948}, issn = {1523-6536}, support = {UM1 AI104681/AI/NIAID NIH HHS/United States ; KL2 TR001115/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; K23 AI135090/AI/NIAID NIH HHS/United States ; T32 HS000032/HS/AHRQ HHS/United States ; T32 CA116339/CA/NCI NIH HHS/United States ; T32 HD094671/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Anaerobiosis ; Anti-Bacterial Agents/therapeutic use ; Child ; *Graft vs Host Disease/drug therapy/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Retrospective Studies ; Transplantation, Homologous ; }, abstract = {Certain anaerobic bacteria are important for maintenance of gut barrier integrity and immune tolerance and may influence the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a single-center retrospective cohort study of allogeneic HSCT recipients to evaluate associations between receipt of antibiotics with an anaerobic spectrum of activity and GVHD outcomes. We identified 1214 children and adults who developed febrile neutropenia between 7 days before and 28 days after HSCT and compared GVHD risk and mortality among patients who received anaerobic antibiotics (piperacillin-tazobactam or carbapenems; n = 491) to patients who received only antibiotics with minimal activity against anaerobes (aztreonam, cefepime, or ceftazidime; n = 723). We performed metagenomic sequencing of serial fecal samples from 36 pediatric patients to compare the effects of specific antibiotics on the gut metagenome. Receipt of anaerobic antibiotics was associated with higher hazards of acute gut/liver GVHD (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.03 to 1.54) and acute GVHD mortality (HR, 1.63; 95% CI, 1.08 to 2.46), but not chronic GVHD diagnosis (HR, 1.04; 95% CI: .84 to 1.28) or chronic GVHD mortality (HR, .88; 95% CI, .53 to 1.45). Anaerobic antibiotics resulted in decreased gut bacterial diversity, reduced abundances of Bifidobacteriales and Clostridiales, and loss of bacterial genes encoding butyrate biosynthesis enzymes from the gut metagenome. Acute gut/liver GVHD was preceded by a sharp decline in bacterial butyrate biosynthesis genes with antibiotic treatment. Our findings demonstrate that exposure to anaerobic antibiotics is associated with increased risks of acute gut/liver GVHD and acute GVHD mortality after allogeneic HSCT. Use of piperacillin-tazobactam or carbapenems should be reserved for febrile neutropenia cases in which anaerobic or multidrug-resistant infections are suspected.}, }
@article {pmid32681922, year = {2021}, author = {Holvoet, T and Joossens, M and Vázquez-Castellanos, JF and Christiaens, E and Heyerick, L and Boelens, J and Verhasselt, B and van Vlierberghe, H and De Vos, M and Raes, J and De Looze, D}, title = {Fecal Microbiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome With Predominant Abdominal Bloating: Short- and Long-term Results From a Placebo-Controlled Randomized Trial.}, journal = {Gastroenterology}, volume = {160}, number = {1}, pages = {145-157.e8}, doi = {10.1053/j.gastro.2020.07.013}, pmid = {32681922}, issn = {1528-0012}, mesh = {Abdominal Pain/etiology/*prevention &amp; control ; Adolescent ; Adult ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Female ; Flatulence/etiology/*prevention &amp; control ; Humans ; Irritable Bowel Syndrome/*complications/*therapy ; Male ; Middle Aged ; Quality of Life ; Surveys and Questionnaires ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with intestinal dysbiosis. Given the reported promising results of open-label fecal microbiota transplantation (FMT) therapy in patients with predominant abdominal bloating, we studied efficacy of this treatment in a randomized, placebo-controlled trial.<br><br>METHODS: Patients with refractory IBS, defined as failure of &#x2265;3 conventional therapies, were randomly assigned to single-dose nasojejunal administration of donor stools (n&#xa0;= 43) or autologous stools (n&#xa0;= 19) in a double-blind study, performed from December 2015 through October 2017, and were followed up for 1 year. IBS-related symptoms were assessed by using a daily symptom diary to determine general abdominal discomfort, abdominal bloating, abdominal pain, and flatulence on a scale of 1-6. Number of daily bowel movements, consistency of the stools, and abdominal circumference were also recorded. Patients completed the IBS-specific quality of life questionnaire. Primary endpoints were improvement of IBS symptoms and bloating at 12 weeks (response). Secondary endpoints were changes in IBS symptom scores and quality of life. Stool samples were collected for microbiota amplicon sequencing. Open-label retransplantation was offered after the trial.<br><br>RESULTS: At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P&#xa0;= .03). Patients given donor stool had significant improvements in level of discomfort (mean reduction, 19%; median score before FMT, 3.98; range, 2.13-6.00; median score after FMT, 3.1; range, 951.29-5.90), stool frequency (mean reduction, 13%; median score before FMT, 2.10; range, 0.57-14.29; median score after FMT 1.7; range, 0.71-4.29), urgency (mean reduction, 38%; median score before FMT, 0.61; range, 0.00-1.00; median score after FMT, 0.37; range, 0.00-1.00), abdominal pain (mean reduction, 26%; median score before FMT, 3.88; range, 1.57-5.17; median score after FMT, 2.80; range, 1.14-4.94), flatulence (mean reduction, 10%; median score before FMT, 3.42; range, 0.71-6.00; median score after FMT, 3.07; range, 0.79-4.23), and quality of life (mean increase, 16%; median score before FMT 32.6; range, 11-119; median score after FMT, 43.1; range, 32.25-99). A significantly higher proportion of women given donor stool (69%) had a response than men (29%) (P&#xa0;= .01). Fecal samples from responders had higher diversity of microbiomes before administration of donor material than fecal samples from nonresponders (P&#xa0;= .04) and distinct baseline composition (P&#xa0;= .04), but no specific marker taxa were associated with response. After single FMT, 21% of patients given donor stool reported effects that lasted for longer than 1 year compared with 5% of patients given placebo stool. A second FMT reduced symptoms in 67% of patients with an initial response to donor&#xa0;stool but not in patients with a prior nonresponse.<br><br>CONCLUSIONS: In a randomized trial of patients with treatment-refractory IBS with predominant bloating, FMT relieved symptoms compared with placebo (autologous transplant), although the effects decreased over 1 year. A second FMT restored the response patients with a prior response. Response was associated with composition of the fecal microbiomes before FMT; this might be used to as a biomarker to select patients for this treatment. ClinicalTrials.gov, Number: NCT02299973.}, }
@article {pmid32681643, year = {2021}, author = {Ghani, R and Mullish, BH and McDonald, JAK and Ghazy, A and Williams, HRT and Brannigan, ET and Mookerjee, S and Satta, G and Gilchrist, M and Duncan, N and Corbett, R and Innes, AJ and Pavlů, J and Thursz, MR and Davies, F and Marchesi, JR}, title = {Disease Prevention Not Decolonization: A Model for Fecal Microbiota Transplantation in Patients Colonized With Multidrug-resistant Organisms.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {72}, number = {8}, pages = {1444-1447}, pmid = {32681643}, issn = {1537-6591}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/P028225/1/MRC_/Medical Research Council/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; MR/T005254/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestines ; }, abstract = {Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia, and length of stay in 20 patients colonized/infected with MDRO receiving FMT (compared with pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.}, }
@article {pmid32681636, year = {2021}, author = {Khanna, S}, title = {Microbiome-based Therapies for Multidrug-resistant Pathobionts: Getting a Step Closer!.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {72}, number = {8}, pages = {1448-1449}, doi = {10.1093/cid/ciaa943}, pmid = {32681636}, issn = {1537-6591}, mesh = {Drug Resistance, Multiple, Bacterial ; Enterococcus ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid32681029, year = {2020}, author = {Jang, YO and Lee, SH and Choi, JJ and Kim, DH and Choi, JM and Kang, MJ and Oh, YM and Park, YJ and Shin, Y and Lee, SW}, title = {Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis.}, journal = {Experimental &amp; molecular medicine}, volume = {52}, number = {7}, pages = {1128-1139}, pmid = {32681029}, issn = {2092-6413}, support = {2019R1F1A1057875//National Research Foundation of Korea (NRF)/International ; 2016R1A6A3A11932575//National Research Foundation of Korea (NRF)/International ; }, mesh = {Administration, Oral ; Animals ; *Apoptosis ; *Diet, High-Fat ; Emphysema/*microbiology/pathology/prevention &amp; control/*therapy ; Fatty Acids/administration &amp; dosage ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Inflammation/*microbiology ; Mice, Inbred C57BL ; Pulmonary Alveoli/pathology ; Weight Loss ; }, abstract = {Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. Here, we demonstrated that gut microbiome modulation attenuated emphysema development. To modulate the gut microbiome, fecal microbiota transplantation (FMT) and diet modification were adopted in mice exposed to smoking and poly I:C for the emphysema model. We analyzed the severity of emphysema by the mean linear intercept (MLI) and apoptosis by the fluorescent TUNEL assay. Microbiome analysis was also performed in feces and fecal extracellular vesicles (EVs). The MLI was significantly increased with smoking exposure. FMT or a high-fiber diet (HFD) attenuated the increase. Weight loss, combined with smoking exposure, was not noted in mice with FMT. HFD significantly decreased macrophages and lymphocytes in bronchoalveolar lavage fluid. Furthermore, IL-6 and IFN-γ were decreased in the bronchoalveolar lavage fluid and serum. The TUNEL score was significantly lower in mice with FMT or HFD, suggesting decreased cell apoptosis. In the microbiome analysis, Bacteroidaceae and Lachnospiraceae, which are alleged to metabolize fiber into short-chain fatty acids (SCFAs), increased at the family level with FMT and HFD. FMT and HFD attenuated emphysema development via local and systemic inhibition of inflammation and changes in gut microbiota composition, which could provide a new paradigm in COPD treatment.}, }
@article {pmid32680797, year = {2021}, author = {Ventero, MP and Espinosa, N and Jover, R and Guillen, Y and Merino, E and Rodríguez, JC}, title = {Evolution of intestinal microbiome in a process of faecal microbiota transfer (FMT) in a patient with Clostridioides difficile infection: NGS analysis with different software programs.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {39}, number = {4}, pages = {184-187}, doi = {10.1016/j.eimc.2020.05.023}, pmid = {32680797}, issn = {2529-993X}, mesh = {Clostridioides ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Software ; }, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) has become a global healthcare challenge due to increases in its incidence and mortality rates. Faecal microbiota transfer (FMT) is postulated as a protocol to prevent CDI recurrence.<br><br>MATERIAL AND METHODS: A donor faecal sample and patient faecal samples (pre-FMT and post-FMT) were analysed. The r16S gene was amplified and sequenced by NGS, and its diversity and taxonomy composition were examined.<br><br>RESULTS: Microbial richness increased in post-FMT samples, and the &#x3b2; diversity studies grouped the samples into two clusters. One included the non-pathological samples (donor and pre-FMT samples), and the other included the pathological sample. The results obtained by Qiime2 and Bioconductor were similar.<br><br>CONCLUSION: The analysis showed an increase in taxonomic diversity after the FMT, which suggests its usefulness. Moreover, these results showed that standardisation of bioinformatics analysis is key.}, }
@article {pmid32679697, year = {2020}, author = {Gentile, P and Sterodimas, A and Pizzicannella, J and Dionisi, L and De Fazio, D and Calabrese, C and Garcovich, S}, title = {Systematic Review: Allogenic Use of Stromal Vascular Fraction (SVF) and Decellularized Extracellular Matrices (ECM) as Advanced Therapy Medicinal Products (ATMP) in Tissue Regeneration.}, journal = {International journal of molecular sciences}, volume = {21}, number = {14}, pages = {}, pmid = {32679697}, issn = {1422-0067}, mesh = {Adipose Tissue/cytology/*transplantation ; Animals ; *Extracellular Matrix/ultrastructure ; Humans ; *Mesenchymal Stem Cell Transplantation/adverse effects/methods ; Mesenchymal Stem Cells/cytology ; *Regenerative Medicine/methods ; Tissue Engineering/methods ; *Tissue Scaffolds/chemistry ; Transplantation, Homologous/adverse effects/methods ; }, abstract = {Stromal vascular fraction (SVF) containing adipose stem cells (ASCs) has been used for many years in regenerative plastic surgery for autologous applications, without any focus on their potential allogenic role. Allogenic SVF transplants could be based on the possibility to use decellularized extracellular matrix (ECM) as a scaffold from a donor then re-cellularized by ASCs of the recipient, in order to develop the advanced therapy medicinal products (ATMP) in fully personalized clinical approaches. A systematic review of this field has been realized in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. Multistep research of the PubMed, Embase, MEDLINE, Pre-MEDLINE, PsycINFO, CINAHL, Clinicaltrials.gov, Scopus database, and Cochrane databases has been conducted to identify articles and investigations on human allogenic ASCs transplant for clinical use. Of the 341 articles identified, 313 were initially assessed for eligibility on the basis of the abstract. Of these, only 29 met all the predetermined criteria for inclusion according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach, and 19 have been included in quantitative synthesis (meta-analysis). Ninety-one percent of the studies previously screened (284 papers) were focused on the in vitro results and pre-clinical experiments. The allogenic use regarded the treatment of perianal fistulas, diabetic foot ulcers, knee osteoarthritis, acute respiratory distress syndrome, refractory rheumatoid arthritis, pediatrics disease, fecal incontinence, ischemic heart disease, autoimmune encephalomyelitis, lateral epicondylitis, and soft tissue defects. The information analyzed suggested the safety and efficacy of allogenic ASCs and ECM transplants without major side effects.}, }
@article {pmid32677955, year = {2020}, author = {Sui, H and Zhang, L and Gu, K and Chai, N and Ji, Q and Zhou, L and Wang, Y and Ren, J and Yang, L and Zhang, B and Hu, J and Li, Q}, title = {YYFZBJS ameliorates colorectal cancer progression in Apc[Min/+] mice by remodeling gut microbiota and inhibiting regulatory T-cell generation.}, journal = {Cell communication and signaling : CCS}, volume = {18}, number = {1}, pages = {113}, pmid = {32677955}, issn = {1478-811X}, mesh = {Adenomatous Polyposis Coli Protein ; Animals ; Bacteroides fragilis ; Bromodeoxyuridine/metabolism ; Carcinogenesis/drug effects/pathology ; Cell Proliferation/drug effects ; Colorectal Neoplasms/*drug therapy/immunology/*microbiology/pathology ; Disease Models, Animal ; *Disease Progression ; Drugs, Chinese Herbal/pharmacology/*therapeutic use ; *Gastrointestinal Microbiome ; HCT116 Cells ; Humans ; Immunity/drug effects ; Ki-67 Antigen/metabolism ; Leukocytes, Mononuclear/drug effects/metabolism ; Lymph Nodes/drug effects/pathology ; Mice ; Mice, Inbred C57BL ; Mucous Membrane/drug effects/pathology ; Proliferating Cell Nuclear Antigen/metabolism ; RNA, Messenger/genetics/metabolism ; Spleen/drug effects/pathology ; T-Lymphocytes, Helper-Inducer/drug effects/immunology ; T-Lymphocytes, Regulatory/drug effects/*immunology ; }, abstract = {BACKGROUND: Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. T cell, one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of CRC. Our previous studies indicate that traditional Chinese herbs (TCM) have potential anticancer effects in improving quality of life and therapeutic effect. However, little is known about the mechanism of TCM formula in cancer prevention.<br><br>METHODS: Here, we used C57BL/6&#x2009;J Apc[Min/+] mice, an animal model of human intestinal tumorigenesis, to investigate the gut bacterial diversity and their mechanisms of action in gastrointestinal adenomas, and to evaluate the effects of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) on of colon carcinogenesis in vivo and in vitro. Through human-into-mice fecal microbiota transplantation (FMT) experiments from YYFZBJS volunteers or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration.<br><br>RESULTS: We report herein, YYFZBJS treatment blocked tumor initiation and progression in Apc[Min/+] mice with less change of body weight and increased immune function. Moreover, diversity analysis of fecal samples demonstrated that YYFZBJS regulated animal's natural gut flora, including Bacteroides fragilis, Lachnospiraceae and so on. Intestinal tumors from conventional and germ-free mice fed with stool from YYFZBJS volunteers had been decreased. Some inflammation' expression also have been regulated by the gut microbiota mediated immune cells. Intestinal lymphatic, and mesenteric lymph nodes (MLN), accumulated CD4+ CD25+ Foxp3 positive Treg cells were reduced by YYFZBJS treatment in Apc[Min/+] mice. Although YYFZBJS had no inhibition on CRC cell proliferation by itself, the altered Tregs mediated by YYFZBJS repressed CRC cancer cell growth, along with reduction of the phosphorylation of &#x3b2;-catenin.<br><br>CONCLUSIONS: In conclusion, we demonstrated that gut microbiota and Treg were involved in CRC development and progression, and we propose YYFZBJS as a new potential drug option for the treatment of CRC. Video abstract.}, }
@article {pmid32677453, year = {2020}, author = {Khanna, S}, title = {Fecal transplant clinical trials for Clostridioides difficile: an interview with Sahil Khanna.}, journal = {Future microbiology}, volume = {15}, number = {}, pages = {709-712}, doi = {10.2217/fmb-2020-0102}, pmid = {32677453}, issn = {1746-0921}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clinical Trials as Topic ; Clostridioides difficile/*drug effects ; Clostridium Infections/epidemiology/microbiology/*therapy ; Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects ; Humans ; }, abstract = {This interview was conducted by Atiya Henry, Commissioning Editor of Future Microbiology. Sahil Khanna is an Associate Professor of Medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic, Rochester (MN, USA). He currently directs the Comprehensive Gastroenterology Interest group, Clostridioides difficile clinic, Fecal Microbiota Transplantation program and C. difficile related clinical trials at Mayo Clinic. He completed Medical School at the All India Institute of Medical Sciences, New Delhi; followed by Post Doctoral Research at University of California, San Diego (CA, USA); residency in Internal Medicine and Fellowship in Gastroenterology and Hepatology at Mayo Clinic, before joining the Faculty. He also completed Masters in Clinical and Translational Sciences during his fellowship. His research and clinical interests include epidemiology, outcomes and emerging therapeutics for C. difficile infection, an arena in which he has had numerous publications and presentations. He has over 100 peer-reviewed publications, serves as reviewer, is on the editorial board of several journals and has won numerous awards.}, }
@article {pmid32677450, year = {2021}, author = {Dubois, NE and Read, CY and O'Brien, K and Ling, K}, title = {Challenges of Screening Prospective Stool Donors for Fecal Microbiota Transplantation.}, journal = {Biological research for nursing}, volume = {23}, number = {1}, pages = {21-30}, doi = {10.1177/1099800420941185}, pmid = {32677450}, issn = {1552-4175}, mesh = {Adult ; Donor Selection/organization &amp; administration/*statistics &amp; numerical data ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Lost to Follow-Up ; Microbiota ; Prospective Studies ; Tissue Donors/*statistics &amp; numerical data ; }, abstract = {Despite high efficacy rates, significant costs and logistical challenges associated with procuring stool from healthy donors for fecal microbiota transplantation (FMT) have presented barriers to broader institutional adoption and limited the availability of this life-saving treatment. Published outcomes for donor screening programs report donor deferral rates between 90% and 96%. Due to the paucity of FMT donor screening data, a secondary analysis on a cohort of previously screened donors (n = 7,968) was conducted to provide a synopsis of the observed trends and rationales for prospective stool donor deferrals. Upon completion of the evaluation, 1.7% of prospective donors (n = 134) qualified for stool donation. Over 50% of donors who completed the online pre-screen were deferred, primarily for a body mass index of 30 kg/m[2] or greater (n = 1,516, 37.0%), logistics (n = 841, 20.5%), and travel history (n = 638, 15.5%). Despite pre-screening, 569 donors (72.8%) who completed the in-person clinical assessment were ultimately deferred due primarily to potentially microbiome-mediated diseases (n = 187, 32.9%). A notably small portion of donors (n = 46, 25.6%) were deferred during the laboratory assessment process suggesting the clinical assessment was effective at deferring donors at higher risk for transmissible diseases. Donors lost to follow-up throughout the screening process presented a significant challenge and contributed to a notable (n = 3,117; 39.1%) portion of donor attrition. Findings were used to support recommendations for improving prospective stool donor screening programs and to provide suggestions for future research.}, }
@article {pmid32675916, year = {2020}, author = {}, title = {Erratum: Faecal microbiota transplantation: indications, evidence and safety [Correction].}, journal = {Australian prescriber}, volume = {43}, number = {3}, pages = {103}, doi = {10.18773/austprescr.2020.032}, pmid = {32675916}, issn = {0312-8008}, abstract = {[This corrects the article on p. 36 in vol. 43, PMID: 32346208.].}, }
@article {pmid32675857, year = {2020}, author = {Dupont, HL and Jiang, ZD and Dupont, AW and Utay, NS}, title = {THE INTESTINAL MICROBIOME IN HUMAN HEALTH AND DISEASE.}, journal = {Transactions of the American Clinical and Climatological Association}, volume = {131}, number = {}, pages = {178-197}, pmid = {32675857}, issn = {0065-7778}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; }, abstract = {The Human Microbiome Initiative of NIH, begun in 2007, has opened the door to the power of the intestinal microbiome in health and disease. The 100 trillion gut microbes influence body function through three pathways: (1) via the neural route where 500 million neurons of the enteric nervous system (the body's second brain) connect to the brain and spinal cord, (2) via the immune route where the gut-immune capacity prevents infection and elicits immune response to vaccines, and (3) by the hormonal route wherein biologically active chemicals are released from enteroendocrine cells to control mood and body functions. Through research, the identification of diseases and disorders associated with abnormal microbiome ("dysbiosis") has increased in number with potential for reversibility. Our team has developed an orally administered fecal microbiota transplantation product that is effective in reversing dysbiosis in recurrent Clostridioides difficile (C. difficile) and is being used to reverse abnormal microbiomes in chronic dysbiotic disorders.}, }
@article {pmid32675782, year = {2021}, author = {Touchefeu, Y and Duchalais, E and Bruley des Varannes, S and Alameddine, J and Mirallie, E and Matysiak-Budnik, T and Le Bastard, Q and Javaudin, F and Rimbert, M and Jotereau, F and Montassier, E}, title = {Concomitant decrease of double-positive lymphocyte population CD4CD8αα and Faecalibacterium prausnitzii in patients with colorectal cancer.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {32}, number = {2}, pages = {149-156}, doi = {10.1097/MEG.0000000000001842}, pmid = {32675782}, issn = {1473-5687}, mesh = {Bacteroides ; Bacteroidetes ; *Colorectal Neoplasms ; *Faecalibacterium prausnitzii ; Humans ; T-Lymphocytes, Regulatory ; }, abstract = {INTRODUCTION AND AIMS: Changes in the composition of the gut microbiota in patients with colorectal cancer (CRC) compatible with a contribution of the gut microbiota in carcinogenesis have been reported. In particular, a decrease Faecalibacterium prausnitzii has been identified. A CD4CD8αα, double-positive lymphocyte population (DP8α) has recently been demonstrated in the human colon and blood with regulatory functions and specificity for F. prausnitzii. Here, we aimed to detect dysbiosis in the fecal microbiome of patients with CRC by metagenomic analysis, and to look for changes in the levels of DP8α circulating T cells specific for F. prausnitzii in these patients.<br><br>PATIENTS AND METHODS: Patients with CRC and control subjects were prospectively included. None had received antibiotics in the previous month or any anti-tumor treatment. A stool sample was collected for each participant, and analyzed by shotgun sequencing. The DP8&#x3b1; T cell population was identified and quantified on fresh whole blood by flow cytometry with anti-CD45, anti-CD3, anti-CD4 and anti-CD8&#x3b1; co-labeling.<br><br>RESULTS: Twenty-one patients with CRC and 20 controls subjects were included. We found that mean relative abundance of five species was significantly decreased in CRC patients compared with controls, including F. prausnitzii, Barnesiella intestinihominis, Alistipes finegoldii, Bacteroides eggerthii and Eubacterium siraeum. We also found that the DP8&#x3b1; T cell population was significantly decreased in the blood of CRC patients compared with controls.<br><br>CONCLUSION: In our work, we showed that a reduced abundance of F. prausnitzii in CRC patients was associated to a significant decrease in the circulating DP8&#x3b1; Treg population, suggesting a potential involvement of reduced activity of DP8&#x3b1; T cells in colonic carcinogenesis. These findings open new diagnostic and therapeutic strategies for CRC.}, }
@article {pmid32675558, year = {2020}, author = {SahBandar, IN and Chew, GM and Corley, MJ and Pang, APS and Tsai, N and Hanks, N and Khadka, VS and Klatt, NR and Hensley-McBain, T and Somsouk, M and Vujkovic-Cvijin, I and Chow, DC and Shikuma, CM and Ndhlovu, LC}, title = {Changes in gastrointestinal microbial communities influence HIV-specific CD8+ T-cell responsiveness to immune checkpoint blockade.}, journal = {AIDS (London, England)}, volume = {34}, number = {10}, pages = {1451-1460}, pmid = {32675558}, issn = {1473-5571}, support = {K01 HL140271/HL/NHLBI NIH HHS/United States ; R56 AI083112/AI/NIAID NIH HHS/United States ; R21 AI122393/AI/NIAID NIH HHS/United States ; R01 DK112254/DK/NIDDK NIH HHS/United States ; DP1 DA037979/DA/NIDA NIH HHS/United States ; U54 GM104944/GM/NIGMS NIH HHS/United States ; R21 DK104664/DK/NIDDK NIH HHS/United States ; P30 AI027757/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Anti-HIV Agents/therapeutic use ; CD8-Positive T-Lymphocytes/*drug effects ; Fecal Microbiota Transplantation ; Female ; Fusobacteria/isolation &amp; purification ; *Gastrointestinal Microbiome ; HIV Infections/drug therapy/*microbiology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Sexual and Gender Minorities ; }, abstract = {OBJECTIVES: The aim of this study was to examine the relationship between gut microbial communities in HIV-infected individuals on suppressive antiretroviral therapy (cART), and the peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo immune checkpoint blockade (ICB).<br><br>DESIGN: Thirty-four HIV-seropositive, 10 HIV-seronegative and 12 HIV-seropositive receiving faecal microbiota transplant (FMT) participants were included. Gut microbial communities, peripheral and gut associated negative checkpoint receptors (NCRs) and peripheral effector functions were assessed.<br><br>METHODS: Bacterial 16s rRNA sequencing for gut microbiome study and flow-based assays for peripheral and gut NCR and their cognate ligand expression, including peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo anti-PD-L1 and anti-TIGIT ICB were performed.<br><br>RESULTS: Fusobacteria abundance was significantly higher in HIV-infected donors compared to uninfected controls. In HIV-infected participants receiving Fusobacteria-free FMT, Fusobacteria persisted up to 24 weeks in stool post FMT. PD-1 TIGIT and their ligands were expanded in mucosal vs. peripheral T cells and dendritic cells, respectively. PD-L1 and TIGIT blockade significantly increased the magnitude of peripheral anti-HIV-Gag-specific CD8 T-cell responses. Higher gut Fusobacteria abundance was associated with lower magnitude of peripheral IFN-&#x3b3;+ HIV-Gag-specific CD8 T-cell responses following ICB.<br><br>CONCLUSION: The gut colonization of Fusobacteria in HIV infection is persistent and may influence anti-HIV T-cell immunity to PD-1 or TIGIT blockade. Strategies modulating Fusobacteria colonization may elicit a favourable mucosal immune landscape to enhance the efficacy of ICB for HIV cure.}, }
@article {pmid32674100, year = {2021}, author = {Fu, X and Chen, Y and Chen, D}, title = {The Role of Gut Microbiome in Autoimmune Uveitis.}, journal = {Ophthalmic research}, volume = {64}, number = {2}, pages = {168-177}, doi = {10.1159/000510212}, pmid = {32674100}, issn = {1423-0259}, mesh = {Animals ; Autoimmune Diseases/*immunology ; Gastrointestinal Microbiome/*immunology ; Humans ; *Immunity, Innate ; Uveitis/*immunology ; }, abstract = {The gut microbiome has important physiological functions and plays an indispensable role in the human body. Currently, there are an increasing number of studies revealing the close correlation between dysbiosis of the gut microbiome and a variety of autoimmune diseases, including autoimmune uveitis. This brief review summarizes recent literature regarding the relationship between dysbiosis and the occurrence and development of autoimmune uveitis. Dysbiosis participates in the pathogenesis of autoimmune uveitis largely by 4 mechanisms: antigenic mimicry, disturbance of intestinal immune homeostasis, destruction of the intestinal barrier, and reduction of beneficial anti-inflammatory metabolites. Further elucidation of these mechanisms will facilitate the treatment of the gut-microbiome-relevant autoimmune diseases by potential therapeutic strategies, such as antibiotics, probiotics, diet modifications, and fecal microbial transplantation.}, }
@article {pmid32671773, year = {2020}, author = {Wang, T and Liu, K and Wen, L and Yang, Y and Yin, X and Liu, K and Chen, Y and He, Y and Yang, M and Wei, Y and Wang, B and Chen, D}, title = {Autophagy and Gastrointestinal Diseases.}, journal = {Advances in experimental medicine and biology}, volume = {1207}, number = {}, pages = {529-556}, doi = {10.1007/978-981-15-4272-5_38}, pmid = {32671773}, issn = {0065-2598}, mesh = {*Autophagy/drug effects ; Cholera ; Crohn Disease ; Gastritis, Atrophic ; *Gastrointestinal Diseases/drug therapy ; Gastrointestinal Neoplasms ; Helicobacter Infections ; Humans ; }, abstract = {Normal gastrointestinal physiology is fundamental for all the living beings. Gastrointestinal diseases mainly include gastrointestinal motility disorders, infectious inflammation (such as Helicobacter pylori infection, cholera, and intestinal parasites), non-infectious inflammation (such as chronic gastritis and Crohn's disease), and gastrointestinal cancers. In addition, intestinal microbial disorder is also an important cause of intestinal diseases, so intestinal microecological treatment (fecal microbiota transplantation) is an important mean of treating gastrointestinal diseases. In recent years, the role of autophagy in gastrointestinal diseases has been studied extensively. Autophagy is observed under various pathological processes of the gastrointestinal tract. For example, it has been demonstrated that autophagy plays an important role in maintaining the homeostasis and integrity of intestinal epithelium. Additionally, autophagy regulates host response to H. pylori infection and development of gastrointestinal cancers. Therefore, we will discuss pivotal roles of autophagy in various gastrointestinal diseases and analyze the underlying molecular mechanisms, which may provide new therapeutic targets applicable for the treatment of gastrointestinal diseases.}, }
@article {pmid32670347, year = {2020}, author = {Qi, X and Zhong, X and Xu, S and Zeng, B and Chen, J and Zang, G and Zeng, L and Bai, S and Zhou, C and Wei, H and Xie, P}, title = {Extracellular Matrix and Oxidative Phosphorylation: Important Role in the Regulation of Hypothalamic Function by Gut Microbiota.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {520}, pmid = {32670347}, issn = {1664-8021}, abstract = {BACKGROUND: In previous studies, our team examined the gut microbiota of healthy individuals and depressed patients using fecal microbiota transplantation of germ-free (GF) mice. Our results showed that depression-like and anxiety-like behavioral phenotypes of host mice were increased, but the molecular mechanism by which gut microbiota regulate host behavioral phenotypes is still unclear.<br><br>METHODS: To investigate the molecular mechanism by which gut microbiota regulate host brain function, adult GF mice were colonized with fecal samples derived from healthy control (HC) individuals or patients with major depressive disorder (MDD). Transcriptomic profiling of hypothalamus samples was performed to detect differentially expressed genes (DEGs). qRT-PCR was used for validation experiments.<br><br>RESULTS: Colonization germ-free (CGF) mice had 243 DEGs compared with GF mice. The most enriched KEGG pathways associated with upregulated genes were "protein digestion and absorption," "extracellular matrix (ECM)-receptor interaction," and "focal adhesion." MDD mice had 642 DEGs compared with HC mice. The most enriched KEGG pathways associated with upregulated genes in MDD mice were also "protein digestion and absorption," "ECM-receptor interaction," and "focal adhesion." Meanwhile, the most enriched KEGG pathway associated with downregulated genes in these mice was "oxidative phosphorylation," and genes related to this pathway were found to be highly correlated in PPI network analysis.<br><br>CONCLUSION: In summary, our findings suggested that regulation of ECM is a key mechanism shared by different gut microbiota and that inhibition of energy metabolism in the hypothalamus by gut microbiota derived from MDD patients is a potential mechanism of behavioral regulation and depression.}, }
@article {pmid32669127, year = {2020}, author = {Lee, KE and Kim, JK and Han, SK and Lee, DY and Lee, HJ and Yim, SV and Kim, DH}, title = {The extracellular vesicle of gut microbial Paenalcaligenes hominis is a risk factor for vagus nerve-mediated cognitive impairment.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {107}, pmid = {32669127}, issn = {2049-2618}, support = {2017R1A5A2014768//National Research Foundation of Korea/International ; }, mesh = {Aging/metabolism ; Alcaligenaceae/*pathogenicity ; Animals ; Cognitive Dysfunction/*etiology/*microbiology ; Colitis/etiology/microbiology ; Escherichia coli/pathogenicity ; *Extracellular Vesicles ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Pilot Projects ; Risk Factors ; Vagotomy ; *Vagus Nerve ; Young Adult ; }, abstract = {BACKGROUND: In a pilot study, we found that feces transplantation from elderly individuals to mice significantly caused cognitive impairment. Paenalcaligenes hominis and Escherichia coli are increasingly detected in the feces of elderly adults and aged mice. Therefore, we isolated Paenalcaligenes hominis and Escherichia coli from the feces of elderly individuals and aged mice and examined their effects on the occurrence of age-related degenerative cognitive impairment and colonic inflammation in mice.<br><br>RESULTS: The transplantation of feces collected from elderly people and aged mice caused significantly more severe cognitive impairment in transplanted young mice than those from young adults and mice. Oral gavage of Paenalcaligenes hominis caused strong cognitive impairment and colitis in specific pathogen-free (SPF) and germ-free mice. Escherichia coli also induced cognitive impairment and colitis in SPF mice. Oral gavage of Paenalcaligenes hominis, its extracellular vesicles (EVs), and/or lipopolysaccharide caused cognitive impairment and colitis in mice. However, celiac vagotomy significantly inhibited the occurrence of cognitive impairment, but not colitis, in mice exposed to Paenalcaligenes hominis or its EVs, whereas its lipopolysaccharide or Escherichia coli had no such effects. Vagotomy also inhibited the infiltration of EVs into the hippocampus.<br><br>CONCLUSIONS: Paenalcaligenes hominis, particularly its EVs, can cause cognitive function-impaired disorders, such as Alzheimer's disease, and its EVs may penetrate the brain through the blood as well as the vagus nerve. Video Abstract.}, }
@article {pmid32668198, year = {2020}, author = {Winkler, ES and Shrihari, S and Hykes, BL and Handley, SA and Andhey, PS and Huang, YS and Swain, A and Droit, L and Chebrolu, KK and Mack, M and Vanlandingham, DL and Thackray, LB and Cella, M and Colonna, M and Artyomov, MN and Stappenbeck, TS and Diamond, MS}, title = {The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Axis.}, journal = {Cell}, volume = {182}, number = {4}, pages = {901-918.e18}, pmid = {32668198}, issn = {1097-4172}, support = {R01 AI123348/AI/NIAID NIH HHS/United States ; P30 AR073752/AR/NIAMS NIH HHS/United States ; R01 AI127513/AI/NIAID NIH HHS/United States ; R01 AI141436/AI/NIAID NIH HHS/United States ; R01 AI143673/AI/NIAID NIH HHS/United States ; T32 AI007163/AI/NIAID NIH HHS/United States ; F30 AI152327/AI/NIAID NIH HHS/United States ; R01 AI152484/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bile Acids and Salts/*metabolism ; Chikungunya Fever/immunology/*pathology/veterinary ; Chikungunya virus/genetics/isolation &amp; purification ; Clostridiales/physiology ; Dendritic Cells/cytology/immunology/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Interferon Type I/*metabolism ; Male ; Membrane Glycoproteins/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes/cytology/immunology/metabolism ; Myeloid Differentiation Factor 88/deficiency/genetics/metabolism ; RNA, Viral/blood ; STAT1 Transcription Factor/deficiency ; Signal Transduction ; Toll-Like Receptor 7/metabolism ; }, abstract = {Chikungunya virus (CHIKV), an emerging alphavirus, has infected millions of people. However, the factors modulating disease outcome remain poorly understood. Here, we show in germ-free mice or in oral antibiotic-treated conventionally housed mice with depleted intestinal microbiomes that greater CHIKV infection and spread occurs within 1 day of virus inoculation. Alteration of the microbiome alters TLR7-MyD88 signaling in plasmacytoid dendritic cells (pDCs) and blunts systemic production of type I interferon (IFN). Consequently, circulating monocytes express fewer IFN-stimulated genes and become permissive for CHIKV infection. Reconstitution with a single bacterial species, Clostridium scindens, or its derived metabolite, the secondary bile acid deoxycholic acid, can restore pDC- and MyD88-dependent type I IFN responses to restrict systemic CHIKV infection and transmission back to vector mosquitoes. Thus, symbiotic intestinal bacteria modulate antiviral immunity and levels of circulating alphaviruses within hours of infection through a bile acid-pDC-IFN signaling axis, which affects viremia, dissemination, and potentially transmission.}, }
@article {pmid32667590, year = {2021}, author = {Generoso, JS and Giridharan, VV and Lee, J and Macedo, D and Barichello, T}, title = {The role of the microbiota-gut-brain axis in neuropsychiatric disorders.}, journal = {Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)}, volume = {43}, number = {3}, pages = {293-305}, pmid = {32667590}, issn = {1809-452X}, support = {R01 AG072491/AG/NIA NIH HHS/United States ; RF1 AG072491/AG/NIA NIH HHS/United States ; }, mesh = {*Autism Spectrum Disorder ; Brain ; *Depressive Disorder, Major ; Ecosystem ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {The microbiota-gut-brain axis is a bidirectional signaling mechanism between the gastrointestinal tract and the central nervous system. The complexity of the intestinal ecosystem is extraordinary; it comprises more than 100 trillion microbial cells that inhabit the small and large intestine, and this interaction between microbiota and intestinal epithelium can cause physiological changes in the brain and influence mood and behavior. Currently, there has been an emphasis on how such interactions affect mental health. Evidence indicates that intestinal microbiota are involved in neurological and psychiatric disorders. This review covers evidence for the influence of gut microbiota on the brain and behavior in Alzheimer disease, dementia, anxiety, autism spectrum disorder, bipolar disorder, major depressive disorder, Parkinson's disease, and schizophrenia. The primary focus is on the pathways involved in intestinal metabolites of microbial origin, including short-chain fatty acids, tryptophan metabolites, and bacterial components that can activate the host's immune system. We also list clinical evidence regarding prebiotics, probiotics, and fecal microbiota transplantation as adjuvant therapies for neuropsychiatric disorders.}, }
@article {pmid32665417, year = {2020}, author = {Kato, S and Shah, A and Plesescu, M and Miyata, Y and Bolleddula, J and Chowdhury, S and Zhu, X}, title = {Prediction of Human Disproportionate and Biliary Excreted Metabolites Using Chimeric Mice with Humanized Liver.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {48}, number = {10}, pages = {934-943}, doi = {10.1124/dmd.120.000128}, pmid = {32665417}, issn = {1521-009X}, mesh = {Animals ; Bile/metabolism ; Biotransformation ; Carbamates/administration &amp; dosage/pharmacokinetics ; Cyproheptadine/administration &amp; dosage/pharmacokinetics ; Drug Evaluation, Preclinical/methods ; *Hepatobiliary Elimination ; Hepatocytes/metabolism/transplantation ; Humans ; Liver/cytology/*metabolism ; Loratadine/administration &amp; dosage/analogs &amp; derivatives/pharmacokinetics ; Male ; Mianserin/administration &amp; dosage/pharmacokinetics ; Mice ; Transplantation Chimera/metabolism ; }, abstract = {The PXB-mouse is potentially a useful in vivo model to predict human hepatic metabolism and clearance. Four model compounds, [[14]C]desloratadine, [[3]H]mianserin, cyproheptadine, and [[3]H]carbazeran, all reported with disproportionate human metabolites, were orally administered to PXB- or control SCID mice to elucidate the biotransformation of each of them. For [[14]C]desloratadine in PXB-mice, O-glucuronide of 3-hydroxydesloratadine was observed as the predominant metabolite in both the plasma and urine. Both 3-hydroxydesloratadine and its O-glucuronide were detected as major drug-related materials in the bile, whereas only 3-hydroxydesloratadine was detected in the feces, suggesting that a fraction of 3-hydroxydesloratadine in feces was derived from deconjugation of its O-glucuronide by gut microflora. This information can help understand the biliary clearance mechanism of a drug and may fill the gap in a human absorption, distribution, metabolism, and excretion study, in which the bile samples are typically not available. The metabolic profiles in PXB-mice were qualitatively similar to those reported in humans in a clinical study in which 3-hydroxydesloratadine and its O-glucuronide were major and disproportionate metabolites compared with rat, mouse, and monkey. In the control SCID mice, neither of the metabolites was detected in any matrix. Similarly, for the other three compounds, all human specific or disproportionate metabolites were detected at a high level in PXB-mice, but they were either minimally observed or not observed in the control mice. Data from these four compounds indicate that studies in PXB-mice can help predict the potential for the presence of human disproportionate metabolites (relative to preclinical species) prior to conducting clinical studies and understand the biliary clearance mechanism of a drug. SIGNIFICANCE STATEMENT: Studies in PXB-mice have successfully predicted the human major and disproportionate metabolites compared with preclinical safety species for desloratadine, mianserin, cyproheptadine, and carbazeran. In addition, biliary excretion data from PXB-mice can help illustrate the human biliary clearance mechanism of a drug.}, }
@article {pmid32665338, year = {2021}, author = {El-Salhy, M}, title = {FMT in IBS: how cautious should we be?.}, journal = {Gut}, volume = {70}, number = {3}, pages = {626-628}, pmid = {32665338}, issn = {1468-3288}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid32664182, year = {2020}, author = {Zhang, S and Lv, J and Ren, X and Hao, X and Zhou, P and Wang, Y}, title = {The efficacy and safety of fecal microbiota transplantation in the treatment of systemic sclerosis: A protocol for systematic review and meta analysis.}, journal = {Medicine}, volume = {99}, number = {28}, pages = {e21267}, pmid = {32664182}, issn = {1536-5964}, mesh = {Adolescent ; Adult ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Male ; Meta-Analysis as Topic ; Middle Aged ; Research Design ; Scleroderma, Systemic/microbiology/*therapy ; Systematic Reviews as Topic ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Systemic sclerosis (SSc) is 1 of the most complex systemic autoimmune diseases.Accumulating evidence suggests that gut microbiota affect the development and function of the immune system and may play a role in the pathogenesis of autoimmune diseases. This new paradigm raises the possibility that many diseases result, at least partially, from microbiota-related dysfunction. This understanding invites the investigation of fecal microbiota transplantation (FMT) in the treatment of SSc. However, no study has specifically and systematically investigated the efficacy and safety of FMT in the treatment of SSc. Thus, this study will systematically and comprehensively appraise the efficacy and safety of FMT in the treatment of SSc.<br><br>METHODS: We will search the following sources without restrictions for date, language, or publication status: PubMed, Web of Science,Cochrane Central Register of Controlled Trials (CENTRAL) Cochrane Library, EMBASE and China National Knowledge Infrastructure. We will apply a combination of Medical Subject Heading (MeSH) and free-text terms incorporating database-specific controlled vocabularies and text words to implement search strategies. We will also search the ongoing trials registered in the World Health Organization's International Clinical Trials Registry Platform. Besides, the previous relevant reviews conducted on FMT for SSc and reference lists of included studies will also be searched.<br><br>RESULTS: This study will provide a reliable basis for the treatment of SSc with FMT.<br><br>CONCLUSIONS: The findings will be an available reference to evaluate the efficacy and safety of FMT in the treatment of SSc.<br><br>REGISTRATION NUMBER: INPLASY202060019.}, }
@article {pmid32663372, year = {2020}, author = {Lim, YY and Lee, YS and Ooi, DSQ}, title = {Engineering the Gut Microbiome for Treatment of Obesity: A Review of Current Understanding and Progress.}, journal = {Biotechnology journal}, volume = {15}, number = {10}, pages = {e2000013}, doi = {10.1002/biot.202000013}, pmid = {32663372}, issn = {1860-7314}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Obesity/therapy ; Prebiotics ; *Probiotics ; }, abstract = {Obesity is a complex, multifactorial disease that is increasing in prevalence despite extensive research and efforts to curb it. Over the last decade, gut microbiome has emerged as an important contributor to the pathogenesis of obesity. Microbiome profile is altered in obese phenotype and the causative role of microbiome in obesity is demonstrated in fecal microbiota transplantation studies. Herein, recent evidences supporting the role of gut microbiome in obesity and the current therapies designed to engineer gut microbiome for treatment of obesity will be reviewed. The microbial enterotypes associated with obesity is outlined, and the gut microbiota-driven metabolism and low-grade inflammation linking gut microbiome and obesity is examined. How the different intrinsic and extrinsic factors such as host genetics, mode of childbirth delivery, diet, lifestyle habits and use of antibiotics influence the composition of the gut microbiome in the development of obesity is evaluated. Also, the efficacy of current microbiome-based therapies in the forms of prebiotics, probiotics and engineered microbes that are used to manipulate gut microbiome in treating obesity is discussed.}, }
@article {pmid32663072, year = {2021}, author = {Matsuoka, K}, title = {Fecal microbiota transplantation for ulcerative colitis.}, journal = {Immunological medicine}, volume = {44}, number = {1}, pages = {30-34}, doi = {10.1080/25785826.2020.1792040}, pmid = {32663072}, issn = {2578-5826}, mesh = {Colitis, Ulcerative/etiology/*microbiology/*therapy ; Dysbiosis/complications/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Altered abundance and composition of the gut microbiota, i.e., dysbiosis, is reported to be involved in the pathogenesis of various diseases including not only gastrointestinal diseases but also metabolic, neurological, and autoimmune disorders. Fecal microbiota transplantation (FMT) aims to correct dysbiosis by administrating feces collected from donors and thus treat the underlying disease. Ulcerative colitis (UC) is a disease characterized by chronic inflammation in the large intestine. Patients with UC have been reported to have dysbiosis, and more specifically, reduced diversity and abundance of the gut microbiota. FMT has been tried as a treatment for UC. Favorable effects of FMT on UC had been reported in case reports or case series. Recently, four randomized controlled trials of FMT for UC were published. Three of the four studies reported that FMT was more effective than control treatment. Thus, FMT is considered as a promising treatment for UC; however, there are many issues to solve before FMT can become a standard therapy for UC including donor selection, administration routes, frequencies, easy-to-administer formulation development, and optimal patient population.}, }
@article {pmid32659381, year = {2021}, author = {Leon-Coria, A and Kumar, M and Workentine, M and Moreau, F and Surette, M and Chadee, K}, title = {Muc2 Mucin and Nonmucin Microbiota Confer Distinct Innate Host Defense in Disease Susceptibility and Colonic Injury.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {11}, number = {1}, pages = {77-98}, pmid = {32659381}, issn = {2352-345X}, support = {//CIHR/Canada ; }, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Colitis/chemically induced/*immunology/pathology ; Colon/drug effects/immunology/microbiology/pathology ; Dextran Sulfate/administration &amp; dosage/toxicity ; Disease Models, Animal ; Disease Resistance/*immunology ; Female ; Gastrointestinal Microbiome/drug effects/*immunology ; Host Microbial Interactions/immunology ; Humans ; *Immunity, Mucosal ; Intestinal Mucosa/drug effects/immunology/microbiology/pathology ; Male ; Mice ; Mice, Knockout ; Mucin-2/genetics/*metabolism ; }, abstract = {BACKGROUND &amp; AIMS: Alterations in intestinal MUC2 mucin and microbial diversity are closely linked with important intestinal pathologies; however, their impact on each other and on intestinal pathogenesis has been vaguely characterized. Therefore, it was of interest in this study to delineate distinct and cooperative function of commensal microbiota and the Muc2 mucus barrier in maintaining intestinal epithelial barrier function.<br><br>METHODS: Muc2 mucin deficient (Muc2[-/-]) and sufficient (Muc2[+/+]) littermates were used as a model for assessing the role of Muc2. To quantify the role of the microbiota in disease pathogenesis, Muc2[+/+] and Muc2[-/-] littermates were treated with a cocktail of antibiotics that reduced indigenous bacteria, and then fecal transplanted with littermate stool and susceptibility to dextran sulphate sodium (DSS) quantified.<br><br>RESULTS: Although, Muc2[+/+] and Muc2[-/-] littermates share similar phyla distribution as evidenced by 16S sequencing they maintain their distinctive gastrointestinal phenotypes. Basally, Muc2[-/-] showed low-grade colonic inflammation with high populations of inflammatory and tolerogenic immune cells that became comparable to Muc2[+/+] littermates following antibiotic treatment. Antibiotics treatment rendered Muc2[+/+] but not Muc2[-/-] littermates highly susceptibility to DSS-induced colitis that was ILC3 dependent. Muc2[-/-] microbiota was colitogenic to Muc2[+/+] as it worsened DSS-induced colitis. Microbiota dependent inflammation was confirmed by bone-marrow chimera studies, as Muc2[-/-] receiving Muc2[+/+] bone marrow showed no difference in their susceptibility toward DSS induced colitis. Muc2[-/-] microbiota exhibited presence of characteristic OTUs of specific bacterial populations that were transferrable to Muc2[+/+] littermates.<br><br>CONCLUSIONS: These results highlight a distinct role for Muc2 mucin in maintenance of healthy microbiota critical in shaping innate host defenses to promote intestinal homeostasis.}, }
@article {pmid32658171, year = {2020}, author = {Blanco, C}, title = {The influence of the gut microbiome on obesity.}, journal = {Journal of the American Association of Nurse Practitioners}, volume = {32}, number = {7}, pages = {504-510}, pmid = {32658171}, issn = {2327-6924}, mesh = {Fecal Microbiota Transplantation/methods/standards ; Gastrointestinal Microbiome/*physiology ; Humans ; Obesity/diet therapy/*physiopathology ; Probiotics/pharmacology/therapeutic use ; Treatment Outcome ; }, abstract = {Obesity is a disease with multiple environmental and genetic factors, which when combined contribute to the maintenance of an elevated body weight, thereby reducing long-term success of weight loss. The human gut microbiome is becoming a new potential contributor to obesity. Specifically, gut bacteria and their metabolites are known to affect dysbiosis, metabolism, endotoxemia, and inflammation. Many environmental and lifestyle factors can alter the gut microbiota affecting obesity. Potential therapies to alter the gut microbiota include supplementation with probiotic organisms and the use of fecal microbiota transplantation. This review will examine the growing evidence supporting the mechanisms with which the human gut microbiota may influence obesity, various influences on the microbiota, and potential therapies.}, }
@article {pmid32657282, year = {2020}, author = {Huang, GQ and Bai, Y and Sun, ZQ and Liu, J}, title = {Successful Treatment of Pseudomembranous Colitis with Fecal Microbiota Transplantation - A Case Study on A Patient Rescued by Extracorporeal Cardiopulmonary Resuscitation After Cardiac Arrest.}, journal = {Annals of transplantation}, volume = {25}, number = {}, pages = {e923283}, pmid = {32657282}, issn = {2329-0358}, mesh = {Adolescent ; Anti-Bacterial Agents/therapeutic use ; Cardiopulmonary Resuscitation/*methods ; Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/complications/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Heart Arrest/microbiology/*therapy ; Humans ; Metronidazole/therapeutic use ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND Pseudomembranous colitis (PMC) is an opportunistic, nosocomial infection caused by Clostridium difficile. CASE REPORT Here we described a patient who developed PMC during her recovery from cardiac arrest. A 16-year-old female high school student experienced sudden cardiac arrest. Spontaneous circulation was not returned by standard cardiopulmonary resuscitation. After her admission to the emergency unit, her cardiac function and neurologic function were finally resumed by extracorporeal cardiopulmonary resuscitation (ECPR); however, after 14 days, her recovery was complicated with excessive diarrhea and shock. Colonoscopy confirmed the diagnosis of PMC. Metronidazole and vancomycin were immediately administered; however, the treatment did not result in any improvement. Fecal microbiota transplantation was then performed, and after 4 transplantations, her diarrhea was significantly ameliorated. After hospital stay for 135 days, the patient was finally discharged with grade II brain function. She later recovered self-care ability in follow-up. CONCLUSIONS The patient suffered from a long-term gastrointestinal ischemia-hypoxia resulting from cardiac arrest. The use of broad-spectrum antibiotics in the later treatment led to refractory PMC, which was successfully managed by multiple fecal microbiota transplantation.}, }
@article {pmid32656839, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome. Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {3}, pages = {557-558}, doi = {10.1111/apt.15875}, pmid = {32656839}, issn = {1365-2036}, mesh = {*Anemia ; Azathioprine ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome ; *Leukopenia ; }, }
@article {pmid32656836, year = {2020}, author = {Segal, JP and Mullish, BH and Quraishi, MN and Iqbal, TH}, title = {Letter: faecal microbiota transplantation for IBS.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {3}, pages = {556-557}, doi = {10.1111/apt.15824}, pmid = {32656836}, issn = {1365-2036}, mesh = {Azathioprine ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome ; }, }
@article {pmid32656604, year = {2021}, author = {Agarwal, A and Maheshwari, A and Verma, S and Arrup, D and Phillips, L and Vinayek, R and Nair, P and Hagan, M and Dutta, S}, title = {Superiority of Higher-Volume Fresh Feces Compared to Lower-Volume Frozen Feces in Fecal Microbiota Transplantation for Recurrent Clostridioides Difficile Colitis.}, journal = {Digestive diseases and sciences}, volume = {66}, number = {6}, pages = {2000-2004}, pmid = {32656604}, issn = {1573-2568}, mesh = {Aged ; Clostridium Infections/*diagnosis/epidemiology/*therapy ; Colitis/*diagnosis/epidemiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; *Freezing/adverse effects ; Humans ; Living Donors ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; }, abstract = {GOALS: To compare the clinical outcomes of different protocols for fecal microbiota transplantation (FMT) in two community hospitals with similar patient demographics.<br><br>BACKGROUND: FMT is commonly performed for recurrent or refractory Clostridioides difficile infection (rCDI). The clinical efficacy of FMT for this indication has been well established. However, there has been no standardization or optimization of the amount of fecal material, method of feces preparation, or route of delivery for FMT.<br><br>STUDY: In this retrospective study, patients with rCDI received FMT using commercially available frozen fecal preparation (22.7&#xa0;g) at Center A and locally prepared fresh fecal filtrate (30-50&#xa0;g) at Center B. The primary outcome was defined as complete resolution of clinical symptoms related to rCDI after at least 8&#xa0;weeks of follow-up.<br><br>RESULTS: Fifty patients from each center were included in the study. Clinical success after initial FMT with lower-volume frozen fecal preparation at Center A was 32/50 (64.0%) compared to 49/50 (98.0%) with higher-volume fresh fecal filtrate at Center B (p&#x2009;<&#x2009;0.0001). Seventeen patients in Center A and 1 patient in Center B underwent at least one repeat FMT. Overall clinical success was achieved in 43/50 (86%) of patients in Center A and 50/50 (100%) in Center B (p&#x2009;=&#x2009;0.012).<br><br>CONCLUSIONS: Our results suggest superior clinical efficacy of a larger amount of fresh fecal filtrate over a smaller amount of commercially available frozen fecal preparation. Further studies are needed to examine the effect of varying amounts of feces and the optimal protocol for FMT in patients with rCDI.}, }
@article {pmid32655675, year = {2020}, author = {Zhu, Y and Zhang, JY and Wei, YL and Hao, JY and Lei, YQ and Zhao, WB and Xiao, YH and Sun, AD}, title = {The polyphenol-rich extract from chokeberry (Aronia melanocarpa L.) modulates gut microbiota and improves lipid metabolism in diet-induced obese rats.}, journal = {Nutrition &amp; metabolism}, volume = {17}, number = {}, pages = {54}, pmid = {32655675}, issn = {1743-7075}, abstract = {The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry (Aronia melanocarpa L.) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the Firmicutes/Bacteroidetes ratio (F/B ratio) and increasing the relative abundance of Bacteroides, Prevotella, Akkermansia and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated Bacteroides, Prevotella and negatively correlated with Clostridium, Eubacterium, Ruminococcaceae. In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis.}, }
@article {pmid32655239, year = {2020}, author = {Ryu, AJ and Rahimi, RS and Leise, MD}, title = {The Current Hepatic Encephalopathy Pipeline.}, journal = {Journal of clinical and experimental hepatology}, volume = {10}, number = {4}, pages = {377-385}, pmid = {32655239}, issn = {0973-6883}, abstract = {Hepatic encephalopathy (HE) is a complication of acute or chronic liver failure; its mechanism is complex, involving multiple organ systems, and is still being elucidated. The standard of care, lactulose, has remained generally unchanged for decades. However, in recent years, better understanding of the pathophysiology has yielded new therapeutic targets for this reversible condition. These novel treatments act both on traditional pathways established in the ammonia hypothesis and through more recently discovered mechanisms. Here, we review contemporary investigational therapies for HE. We used narrative reviews and searched ClinicalTrials.gov database for the condition "hepatic encephalopathy" through August 29, 2019. Our review yielded six key areas of therapeutic focus: (1) antibiotics against urease-producing gut bacteria, (2) intravenous ammonia scavengers, (3) modified synthetic probiotics, (4) fecal microbiota transplant, (5) brain steroid-modulating agents, and 6) nonlactulose laxatives. Active trials are ongoing in each of these therapeutic areas.}, }
@article {pmid32651763, year = {2020}, author = {Akobeng, AK and Singh, P and Kumar, M and Al Khodor, S}, title = {Role of the gut microbiota in the pathogenesis of coeliac disease and potential therapeutic implications.}, journal = {European journal of nutrition}, volume = {59}, number = {8}, pages = {3369-3390}, pmid = {32651763}, issn = {1436-6215}, mesh = {*Celiac Disease ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Infant ; Prebiotics ; *Probiotics ; }, abstract = {PURPOSE: Although genetic predisposition and exposure to dietary gluten are considered necessary triggers for the development of coeliac disease, alterations in the gut microbial composition may also contribute towards the pathogenesis of coeliac disease. This review aims to provide an overview of the available data on the potential mechanisms through which the gut microbiota plays a role in the causation of coeliac disease and to discuss the potential therapeutic strategies that could diminish the consequences of microbial dysbiosis.<br><br>METHOD: A search of the literature was performed using the PubMed, Embase, and JSTOR databases; relevant articles were included.<br><br>RESULTS: Recent studies in patients with coeliac disease have reported an increase in the relative amounts of gram negative bacterial genera such as Bacteroides, Prevotella, and Escherichia, and reduced amounts of protective anti-inflammatory bacteria such as Bifidobacteria and Lactobacilli. Dysbiotic microbiota may lead to a dysregulated immune response that may contribute to the pathogenesis of coeliac disease. In infancy, antibiotic use and certain infant feeding practices may lead to alterations in the developing gut microbiota to influence the immune maturation process and predispose to coeliac disease.<br><br>CONCLUSION: The induction of the intestinal immune system and gluten intolerance may be influenced by the relative abundance of certain microbiota. Factors such as infant feeding practices, diet, antibiotics, and infections, may be involved in the development of coeliac disease due to their influence on gut microbial composition. The efficacy of potential modulators of the gut microbiota such as probiotics, prebiotics, and fecal microbial transplant as adjunctive treatments to gluten-free diet in coeliac disease is unproven and requires further investigation.}, }
@article {pmid32649987, year = {2020}, author = {Keskey, R and Cone, JT and DeFazio, JR and Alverdy, JC}, title = {The use of fecal microbiota transplant in sepsis.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {226}, number = {}, pages = {12-25}, pmid = {32649987}, issn = {1878-1810}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 GM062344/GM/NIGMS NIH HHS/United States ; }, mesh = {Brain/physiopathology ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Immunophenotyping ; Sepsis/immunology/*therapy ; }, abstract = {Sepsis is defined as a dysregulated inflammatory response, which ultimately results from a perturbed interaction of both an altered immune system and the biomass and virulence of involved pathogens. This response has been tied to the intestinal microbiota, as the microbiota and its associated metabolites play an essential role in regulating the host immune response to infection. In turn, critical illness as well as necessary health care treatments result in a collapse of the intestinal microbiota diversity and a subsequent loss of health-promoting short chain fatty acids, such as butyrate, leading to the development of a maladaptive pathobiome. These perturbations of the microbiota contribute to the dysregulated immune response and organ failure associated with sepsis. Several case series have reported the ability of fecal microbiota transplant (FMT) to restore the host immune response and aid in recovery of septic patients. Additionally, animal studies have revealed the mechanism of FMT rescue in sepsis is likely related to the ability of FMT to restore butyrate producing bacteria and alter the innate immune response aiding in pathogen clearance. However, several studies have reported lethal complications associated with FMT, including bacteremia. Therefore, FMT in the treatment of sepsis is and should remain investigational until a more detailed mechanism of how FMT restores the host immune response in sepsis is determined, allowing for the development of more fine-tuned microbiota therapies.}, }
@article {pmid32645991, year = {2020}, author = {Shin, YC and Shin, W and Koh, D and Wu, A and Ambrosini, YM and Min, S and Eckhardt, SG and Fleming, RYD and Kim, S and Park, S and Koh, H and Yoo, TK and Kim, HJ}, title = {Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip.}, journal = {Micromachines}, volume = {11}, number = {7}, pages = {}, pmid = {32645991}, issn = {2072-666X}, support = {RR160093//Cancer Prevention and Research Institute of Texas/ ; 1912-03604//Leona M. and Harry B. Helmsley Charitable Trust/ ; F99 CA245801/CA/NCI NIH HHS/United States ; UTA18-000889/CRI/Cancer Research Institute/United States ; R21CA236690//National Cancer Institute of the National Institutes of Health/ ; BWF 1019990.01//Burroughs Wellcome Fund Collaborative Research Travel Grant/ ; F99CA245801//National Cancer Institute of the National Institutes of Health (NIH/NCI)/ ; R21 CA236690/CA/NCI NIH HHS/United States ; 771066//American College of Veterinary Internal Medicine Advance Research Fellowships/ ; 2018M3A9H3025030//Ministry of Science and ICT, South Korea/ ; K00 CA245801/CA/NCI NIH HHS/United States ; }, abstract = {The regeneration of the mucosal interface of the human intestine is critical in the host-gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn's disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic-oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host-microbiome crosstalk to target a patient-specific disease modeling.}, }
@article {pmid32645451, year = {2021}, author = {Cheng, YW and Alhaffar, D and Saha, S and Khanna, S and Bohm, M and Phelps, E and Ghabril, M and Orman, E and Sashidhar, S and Rogers, N and Xu, H and Khoruts, A and Vaughn, B and Kao, D and Wong, K and Cammarota, G and Ianiro, G and Dhere, T and Kraft, CS and Mehta, N and Woodworth, MH and Allegretti, JR and Nativ, L and Marcus, J and El-Nachef, N and Fischer, M}, title = {Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {19}, number = {8}, pages = {1627-1634}, pmid = {32645451}, issn = {1542-7714}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; }, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; *End Stage Liver Disease ; Fecal Microbiota Transplantation/adverse effects ; Humans ; Liver Cirrhosis/complications/therapy ; Recurrence ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis.<br><br>METHODS: We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT.<br><br>RESULTS: Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child-Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P&#xa0;= .003), had pseudomembranes (22.2% vs 0; P&#xa0;= .018), and underwent FMT as inpatients (45.5% vs 19%; P&#xa0;= .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P&#xa0;= .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P&#xa0;= .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death.<br><br>CONCLUSIONS: In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.}, }
@article {pmid32643046, year = {2020}, author = {Yoshimitsu, M and Egi, H and Nagamatsu, S and Shimomura, M and Hakoda, K and Miguchi, M and Kohashi, T and Okajima, M and Ohdan, H}, title = {Gluteal-fold flap repair of rectovaginal fistula caused by aluminum potassium sulfate hydrate-tannic acid injection for internal hemorrhoids: a case report.}, journal = {Surgical case reports}, volume = {6}, number = {1}, pages = {166}, pmid = {32643046}, issn = {2198-7793}, abstract = {BACKGROUND: Rectovaginal fistula (RVF) following aluminum potassium sulfate hydrate-tannic acid (ALTA) injection therapy for hemorrhoids is a rare complication. We report the first case of RVF after ALTA injection therapy successfully treated by gluteal-fold flap.<br><br>CASE PRESENTATION: A 49-year-old female suffered from a fever and rectal ulcer after undergoing internal hemorrhoid treatment with a submucosal ALTA injection at a previous clinic. One week after ALTA therapy, she noted obvious passage of flatus and stool through the vagina, and was diagnosed with RVF by anoscope at another clinic. She was referred to our hospital 3&#x2009;weeks after ALTA therapy. Sigmoid colostomy was performed for fecal diversion as a preliminary step for fistula repair. However, the fistula was scarred and the defect between the rectum and vagina did not improve at all. Ten months after ALTA therapy, we performed fistula repair by gluteal-fold flap. Seven months later, sigmoid-colostomy reversal was performed. The patient has experienced no RVF in the 3&#x2009;years since sigmoid-colostomy reversal.<br><br>CONCLUSIONS: The gluteal-fold flap strategy is a useful option for severe RVF management.}, }
@article {pmid32642633, year = {2020}, author = {Hvas, CL and Baunwall, SMD and Erikstrup, C}, title = {Faecal microbiota transplantation: A life-saving therapy challenged by commercial claims for exclusivity.}, journal = {EClinicalMedicine}, volume = {24}, number = {}, pages = {100436}, pmid = {32642633}, issn = {2589-5370}, abstract = {Faecal microbiota transplantation (FMT) is an innovative treatment which is challenged by a regulatory struggle in Europe. A recent publication in EClinicalMedicine describes the successful adaptation of FMT to a National drug legislation, but this approach fails to take into account the donor-related aspects. The European tissue and cells directive and affiliated technical guide provide extensive safety and quality standards which may readily be adopted in an FMT service to provide patients with this life-saving treatment embedded in a public blood centre.}, }
@article {pmid32641428, year = {2020}, author = {Seekatz, AM}, title = {mSphere of Influence: Translating Gut Microbiome Studies To Benefit Human Health.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32641428}, issn = {2379-5042}, support = {K01 DK111794/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*genetics ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics/physiology ; Germ-Free Life ; *Health ; High-Throughput Nucleotide Sequencing ; Humans ; Mice ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Twins, Monozygotic ; }, abstract = {Anna M. Seekatz works in the field of the gut microbiome as it related to infectious diseases. In this "mSphere of Influence" article, she reflects on how two studies, "The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins" (N. P. McNulty, T. Yatsunenko, A. Hsiao, et al., Sci Transl Med 3:106ra106, 2011) and "High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria" (M. J. Hamilton, A. R. Weingarden, T. Unno, A. Khoruts, and M. J. Sadowsky, Gut Microbes 4:125-135, 2013), shaped how she approaches interpreting microbiome studies.}, }
@article {pmid32639360, year = {2020}, author = {Van den Houte, K and Colomier, E and Schol, J and Carbone, F and Tack, J}, title = {Recent advances in diagnosis and management of irritable bowel syndrome.}, journal = {Current opinion in psychiatry}, volume = {33}, number = {5}, pages = {460-466}, pmid = {32639360}, issn = {1473-6578}, mesh = {*Diet ; Disease Management ; Fermentation ; Gastrointestinal Microbiome/*physiology ; Humans ; Irritable Bowel Syndrome/*diagnosis/*diet therapy/physiopathology ; *Probiotics ; }, abstract = {PURPOSE OF REVIEW: This review summarizes recent progress in the diagnosis and management of irritable bowel syndrome, with a focus on dietary and microbiota aspects.<br><br>RECENT FINDINGS: From a pathophysiological point of view, IBS is a multifactorial condition with both peripheral (transit) as central (visceral hypersensitivity, anxiety, depression) contribution in a cumulative fashion to the symptom pattern and severity. More recently, the focus has shifted to diet and microbiota. The number of dietary options that can be used for IBS and the understanding of determinants of their efficacy is rapidly increasing. Several studies have confirmed the efficacy of the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. Sucrose-isomaltase deficiency has emerged as pathogenetic mechanisms in a subset of patients, who do not respond to low FODMAP diet but may respond to starch and sucrose elimination. Herbal remedies, probiotics and secretagogues have been the topic of additional treatment trials. The efficacy of fecal microbiota transplantation in IBS is variable across studies, but donor selection is emerging as a critical factor.<br><br>SUMMARY: Irritable bowel syndrome has evolved into a disorder of interaction between dietary factors and gut microbiota, with impact on bowel symptoms as well as extra-intestinal, central, symptoms. Dietary adjustments and treatments targeting the gut microbiota are areas of active research and clinical progress.}, }
@article {pmid32639105, year = {2020}, author = {Stone, JM and Savage, A and Hudspeth, M and Twombley, K and Kasi, N and Quiros, JA and Arbizu, RA and Curry, S}, title = {Multi-organism gastrointestinal polymerase chain reaction positivity among pediatric transplant vs non-transplant populations: A single-center experience.}, journal = {Pediatric transplantation}, volume = {24}, number = {6}, pages = {e13771}, pmid = {32639105}, issn = {1399-3046}, support = {K23 AI125607/AI/NIAID NIH HHS/United States ; P30 DK123704/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Child, Preschool ; Clostridioides difficile ; Cryptosporidiosis ; Cryptosporidium ; Diarrhea/*complications/*microbiology ; Enteropathogenic Escherichia coli ; Feces/microbiology/virology ; Female ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Norovirus ; Organ Transplantation/adverse effects ; Pediatrics/*methods ; Polymerase Chain Reaction ; Quality of Life ; Retrospective Studies ; Sapovirus ; Treatment Outcome ; }, abstract = {BACKGROUND: Diarrhea is a common problem in the pediatric post-solid organ transplant and post-hematopoietic stem cell transplant populations. Infectious etiology incidences are poorly defined, and the possibility of multi-organism positivity is often uninvestigated. The aim of this study is to utilize stool multiplex GIP assays to compare the PTP and NTP regarding the incidence and profiles of single-organism and multi-organism infectious diarrhea.<br><br>METHODS: A single-center retrospective review was conducted, investigating stool multiplex GIP panel results over a more than 3-year period, for pediatric patients. Assays test for 23 viral, bacterial, and protozoal organisms.<br><br>RESULTS: Positive assays in the PTP and NTP were 70/101 (69.3%) and 962/1716 (56.1%), respectively (P&#xa0;=&#xa0;.009). Thirty-two percent (32/101) of assays within the PTP were multi-organism positive, significantly more than 14.8% (254/1716) in the NTP (P&#xa0;<&#xa0;.00001). There was no significant difference in the incidence of single-organism positives, 37.6% (38/101) in PTP and 41.3% (708/1716) in the NTP. The PTP demonstrated a statistically significantly higher incidence of the following organisms within multi-agent positive GIPs (P&#xa0;<&#xa0;.05 for each): Clostridioides difficile, Cryptosporidium, EPEC, norovirus, and sapovirus.<br><br>CONCLUSIONS: The pediatric PTP demonstrates higher incidence of positive GIPs, higher rate of multi-organism positivity, and unique infectious organism incidence profiles. These data can provide a framework for understanding organism-specific pathogenicity factors, assessing the clinical impact of enteric co-infection, and understanding the utility of this testing modality in this unique population.}, }
@article {pmid32637898, year = {2020}, author = {Abdali, ZI and Roberts, TE and Barton, P and Hawkey, PM}, title = {Economic evaluation of Faecal microbiota transplantation compared to antibiotics for the treatment of recurrent Clostridioides difficile infection.}, journal = {EClinicalMedicine}, volume = {24}, number = {}, pages = {100420}, pmid = {32637898}, issn = {2589-5370}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is a hospital acquired disease associated with significant morbidity, hospitalisation and mortality. Almost 30% of treated patients experience at least one recurrence after treatment of their first episode. Treatment of recurrent CDI (rCDI) utilises vancomycin or fidaxomicin, however, a newer treatment option is faecal microbial transplantation (FMT) administered by nasogastric tube (NGT) or colonoscopy. It is associated with higher cure and lower recurrence rates than fidaxomicin or vancomycin. The aim of this analysis is to evaluate the cost effectiveness of FMT for rCDI using the latest and best evidence.<br><br>METHOD: A cost utility analysis was conducted using a decision model representing the cost per additional Quality Adjusted Life Year (QALY) from a National Health Service (NHS) perspective. A Markov model was constructed to compare FMT NGT and colonoscopy to antibiotic treatment (fidaxomicin or vancomycin). The model was informed by a literature review of clinical evidence, specifically focussing on hospitalised patients with rCDI over 65 years. Both deterministic and probabilistic sensitivity analyses were performed to assess uncertainties around the model inputs and assumptions.<br><br>FINDINGS: The base case analysis showed that FMT is a less costly and more effective treatment than either fidaxomicin or vancomycin. FMT colonoscopy was slightly more effective than FMT NGT leading to an additional 0.012 QALYs but more expensive and the incremental cost effectiveness ratio (ICER) was &#xa3;242,514/QALY. The Probabilistic sensitivity analysis based on 10,000 simulations suggested the probability of FMT NGT being cost effective was almost 78% at &#xa3;20,000/QALY Willingness-To-Pay (WTP) threshold.<br><br>INTERPRETATION: FMT is both more effective and less costly option than antimicrobial therapy. FMT NGT was the preferred route of administration and is likely to be considered the most cost-effective strategy by decision makers given current acceptable thresholds.}, }
@article {pmid32636823, year = {2020}, author = {Moreno-Indias, I and Lundberg, R and Krych, L and Metzdorff, SB and Kot, W and Sørensen, DB and Nielsen, DS and Hansen, CHF and Hansen, AK}, title = {A Humanized Diet Profile May Facilitate Colonization and Immune Stimulation in Human Microbiota-Colonized Mice.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1336}, pmid = {32636823}, issn = {1664-302X}, abstract = {BACKGROUND: In spite of the importance of the use of gnotobiotic mice for human fecal transfer, colonization efficiency and immune stimulation after human microbiota inoculation in mice are poorly studied compared to mouse microbiota inoculation. We tested the colonization efficiency and immune responses in mice bred for one additional generation after inoculating the parent generation with either a human (HM) or a mouse microbiota (MM). Furthermore, we tested if colonization efficiency and immune stimulation could be improved in HM-colonized mice by dietary approaches: if these were fed a diet closer to the human diet either in its sources of animal fat and protein [the "animal source" (AS) diet] or in its proportions of macronutrients from the normal sources of a mouse diet [the "human profile" (HP) diet].<br><br>RESULTS: Although significantly lower in mice with a human microbiota (30-40% vs. 61-70%) the colonization efficiency was significantly higher in HM mice fed the HP diet (40%), and in MM mice fed AS (70%). The microbiota of mice fed HP was comparable to the microbiota of mice fed a standard rodent chow, while the microbiota of mice fed the animal source diet (AS) clustered separately. Mice inoculated with mouse fecal matter had significantly more CD4[+] T cells and Cd4 expression and significantly fewer regulatory T cells (Tregs) and FoxP3 expression than human microbiota inoculated mice, but cell proportions differences were mostly apparent between mice fed the AS diet. Mice fed the HP diet had significantly higher expression of Cd8a.<br><br>CONCLUSION: It is concluded that a diet with a humanized profile could support the establishment of a human microbiota in mice, which will, however, still elicit a lower colonization efficiency compared to mice inoculated with a mouse microbiota.}, }
@article {pmid32635553, year = {2020}, author = {Hahn, A and Frickmann, H and Zautner, AE}, title = {Impact of Case Definitions on Efficacy Estimation in Clinical Trials-A Proof-of-Principle Based on Historical Examples.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {7}, pages = {}, pmid = {32635553}, issn = {2079-6382}, support = {DFG ZA 697/6-1//Deutsche Forschungsgemeinschaft/ ; not applicable//Forschungsf&#xf6;rderungsprogramm of the Universit&#xe4;tsmedizin G&#xf6;ttingen (UMG), Germany/ ; not applicable//Open Access Support Program of the Deutsche Forschungsgemeinschaft/ ; not applicable//publication fund of the Georg-August-Universit&#xe4;t G&#xf6;ttingen/ ; }, abstract = {Efficacy estimations in clinical trials are based on case definitions. Commonly, they are a more or less complex set of conditions that have to be fulfilled in order to define a clinical case. In the simplest variant, such a case is identical with a single positive diagnostic test result. Frequently, however, case definitions are more complex. Further, their conditions often ignore the inherent logical structure of symptoms and disease: A symptom or a set of symptoms may be necessary but not sufficient for the unambiguous identification of a case. After describing the structure of case definitions and its impact on efficacy estimations, we exemplify this impact using data from two clinical trials dealing with the effectiveness of the vaginal application of tenofovir gel for the prevention of HIV infections and with the therapeutic effects of fecal transplantation on recurrent Clostridium difficile infections. We demonstrate that the diagnostic performance of case definitions affects efficacy estimations for interventions in clinical trials. The potential risk of bias and uncertainty is high, irrespective of the complexity of the case definition. Accordingly, case definitions in clinical trials should focus on specificity in order to avoid the risk of bias.}, }
@article {pmid32635373, year = {2020}, author = {Johnson, D and Letchumanan, V and Thurairajasingam, S and Lee, LH}, title = {A Revolutionizing Approach to Autism Spectrum Disorder Using the Microbiome.}, journal = {Nutrients}, volume = {12}, number = {7}, pages = {}, pmid = {32635373}, issn = {2072-6643}, support = {Project No. PVC-ECR-2016, Biotek Abadi - Vote No. GBA-808138 and GBA-808813//PVC Award Grant &amp; External Industry Grant/ ; }, mesh = {Autism Spectrum Disorder/*microbiology/therapy ; Diet/methods ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Microbiota/*physiology ; Mouth/microbiology ; Prebiotics ; Probiotics/therapeutic use ; Vagina/microbiology ; }, abstract = {The study of human microbiota and health has emerged as one of the ubiquitous research pursuits in recent decades which certainly warrants the attention of both researchers and clinicians. Many health conditions have been linked to the gut microbiota which is the largest reservoir of microbes in the human body. Autism spectrum disorder (ASD) is one of the neurodevelopmental disorders which has been extensively explored in relation to gut microbiome. The utilization of microbial knowledge promises a more integrative perspective in understanding this disorder, albeit being an emerging field in research. More interestingly, oral and vaginal microbiomes, indicating possible maternal influence, have equally drawn the attention of researchers to study their potential roles in the etiopathology of ASD. Therefore, this review attempts to integrate the knowledge of microbiome and its significance in relation to ASD including the hypothetical aetiology of ASD and its commonly associated comorbidities. The microbiota-based interventions including diet, prebiotics, probiotics, antibiotics, and faecal microbial transplant (FMT) have also been explored in relation to ASD. Of these, diet and probiotics are seemingly promising breakthrough interventions in the context of ASD for lesser known side effects, feasibility and easier administration, although more studies are needed to ascertain the actual clinical efficacy of these interventions. The existing knowledge and research gaps call for a more expanded and resolute research efforts in establishing the relationship between autism and microbiomes.}, }
@article {pmid32632657, year = {2020}, author = {Birkeland, E and Gharagozlian, S and Birkeland, KI and Valeur, J and Måge, I and Rud, I and Aas, AM}, title = {Correction to: Prebiotic effect of inulin‑type fructans on faecal microbiota and short‑chain fatty acids in type 2 diabetes: a randomised controlled trial.}, journal = {European journal of nutrition}, volume = {59}, number = {7}, pages = {3339-3340}, doi = {10.1007/s00394-020-02314-0}, pmid = {32632657}, issn = {1436-6215}, abstract = {The original version of this article unfortunately contained a mistake. The presentation of Fig. 4 was incorrect.}, }
@article {pmid32632582, year = {2020}, author = {Giacobbe, DR and Dettori, S and Di Bella, S and Vena, A and Granata, G and Luzzati, R and Petrosillo, N and Bassetti, M}, title = {Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies.}, journal = {Infectious diseases and therapy}, volume = {9}, number = {3}, pages = {481-494}, pmid = {32632582}, issn = {2193-8229}, abstract = {Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) remain associated with a reduction in the patients' quality of life and with increased healthcare costs. Bezlotoxumab is a monoclonal antibody against toxin B of C. difficile, approved for prevention of rCDI. In this narrative review, we briefly discuss the pathophysiology of CDI and the mechanism of action of bezlotoxumab, as well as the available evidence from investigational and observational studies in terms of efficacy, effectiveness, and safety of bezlotoxumab for the prevention of rCDI. Overall, bezlotoxumab has proved efficacious in reducing the burden of rCDI, thereby providing clinicians with an important novel strategy to achieve sustained cure. Nonetheless, experiences outside randomized controlled trials (RCTs) remain scant, and mostly represented by case series without a control group. Along with the conduction of RCTs to directly compare bezlotoxumab with faecal microbiota transplantation (or to precisely evaluate the role of their combined use), further widening our post-marketing experience remains paramount to firmly guide the use of bezlotoxumab outside RCTs, and to clearly identify those real-life settings where its preventive benefits can be exploited most.}, }
@article {pmid32631492, year = {2020}, author = {Alavi, S and Mitchell, JD and Cho, JY and Liu, R and Macbeth, JC and Hsiao, A}, title = {Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection.}, journal = {Cell}, volume = {181}, number = {7}, pages = {1533-1546.e13}, pmid = {32631492}, issn = {1097-4172}, support = {R35 GM124724/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Animals ; Bile Acids and Salts ; Cholera/*metabolism/microbiology ; Disease Models, Animal ; Disease Susceptibility/*microbiology ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/*physiology ; Host-Pathogen Interactions/physiology ; Humans ; Hydrolases/analysis ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; Taurocholic Acid/metabolism ; Vibrio cholerae/pathogenicity/physiology ; Virulence ; }, abstract = {The gut microbiome is the resident microbial community of the gastrointestinal tract. This community is highly diverse, but how microbial diversity confers resistance or susceptibility to intestinal pathogens is poorly understood. Using transplantation of human microbiomes into several animal models of infection, we show that key microbiome species shape the chemical environment of the gut through the activity of the enzyme bile salt hydrolase. The activity of this enzyme reduced colonization by the major human diarrheal pathogen Vibrio cholerae by degrading the bile salt taurocholate that activates the expression of virulence genes. The absence of these functions and species permits increased infection loads on a personal microbiome-specific basis. These findings suggest new targets for individualized preventative strategies of V. cholerae infection through modulating the structure and function of the gut microbiome.}, }
@article {pmid32629118, year = {2020}, author = {Su, CW and Chen, CY and Jiao, L and Long, SR and Mao, T and Ji, Q and O'Donnell, S and Stanton, C and Zheng, S and Walker, WA and Cherayil, BJ and Shi, HN}, title = {Helminth-Induced and Th2-Dependent Alterations of the Gut Microbiota Attenuate Obesity Caused by High-Fat Diet.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {10}, number = {4}, pages = {763-778}, pmid = {32629118}, issn = {2352-345X}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R56 AI089700/AI/NIAID NIH HHS/United States ; R01 AI089700/AI/NIAID NIH HHS/United States ; R21 AI121997/AI/NIAID NIH HHS/United States ; R21 AI144738/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cells, Cultured ; Diet, High-Fat/*adverse effects ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Nematospiroides dubius/*immunology ; Obesity/etiology/immunology/*prevention &amp; control ; Protective Factors ; Strongylida Infections/immunology ; }, abstract = {BACKGROUND &amp; AIMS: Epidemiological and animal studies have indicated an inverse correlation between the rising prevalence of obesity and metabolic syndrome and exposure to helminths. Whether helminth-induced immune response contributes to microbiota remodeling in obesity remains unknown. The aim of this study is to explore the immune-regulatory role of helminth in the prevention of HFD-induced obesity through remodeling gut microbiome.<br><br>METHODS: C57BL/6J WT and STAT6[-/-] mice were infected with Heligmosomoides polygyrus and followed by high fat diet (HFD) feeding for 6 weeks. The host immune response, body weight, and fecal microbiota composition were analyzed. We used adoptive transfer of M2 macrophages and microbiota transplantation approaches to determine the impact of these factors on HFD-obesity. We also examined stool microbiota composition and short chain fatty acids (SCFAs) concentration and determined the expression of SCFA-relevant receptors in the recipient mice.<br><br>RESULTS: Helminth infection of STAT6[-/-] (Th2-deficient) mice and adoptive transfer of helminth-induced alternatively activated (M2) macrophages demonstrated that the helminth-associated Th2 immune response plays an important role in the protection against obesity and induces changes in microbiota composition. Microbiota transplantation showed that helminth-induced, Th2-dependent alterations of the gut microbiota are sufficient to confer protection against obesity. Collectively, these results indicate that helminth infection protects against HFD-induced obesity by Th2-dependent, M2 macrophage-mediated alterations of the intestinal microbiota.<br><br>CONCLUSION: Our findings provide new mechanistic insights into the complex interplay between helminth infection, the immune system and the gut microbiota in a HFD-induced obesity model and holds promise for gut microbiome-targeted immunotherapy in obesity prevention.}, }
@article {pmid32625197, year = {2020}, author = {Ojima, MN and Gotoh, A and Takada, H and Odamaki, T and Xiao, JZ and Katoh, T and Katayama, T}, title = {Bifidobacterium bifidum Suppresses Gut Inflammation Caused by Repeated Antibiotic Disturbance Without Recovering Gut Microbiome Diversity in Mice.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1349}, pmid = {32625197}, issn = {1664-302X}, abstract = {The gut microbiome is a dynamic community that significantly affects host health; it is frequently disturbed by medications such as antibiotics. Recently, probiotics have been proposed as a remedy for antibiotic-induced dysbiosis, but the efficacy of such treatments remains uncertain. Thus, the effect of specific antibiotic-probiotic combinations on the gut microbiome and host health warrants further research. We tested the effect vancomycin, amoxicillin, and ciprofloxacin on mice. Antibiotic administration was followed by one of the following recovery treatments: Bifidobacterium bifidum JCM 1254 as a probiotic (PR); fecal transplant (FT); or natural recovery (NR). Each antibiotic administration and recovery treatment was repeated three times over 9 weeks. We used the Shannon Index and Chao1 Index to determine gut microbiome diversity and assessed recovery by quantifying the magnitude of microbial shift using the Bray-Curtis Index of Dissimilarity. We determined the community composition by sequencing the V3-V4 regions of the 16S ribosomal RNA gene. To assess host health, we measured body weight and cecum weight, as well as mRNA expression of inflammation-related genes by reverse-transcription quantitative PCR. Our results show that community response varied by the type of antibiotic used, with vancomycin having the most significant effects. As a result, the effect of probiotics and fecal transplants also varied by antibiotic type. For vancomycin, the first antibiotic disturbance substantially increased the relative abundance of inflammatory species in the phylum Proteobacteria, such as Proteus, but the effect of subsequent disturbances was less pronounced, suggesting that the gut microbiome is affected by past disturbance events. Furthermore, although gut microbiome diversity did not recover, probiotic supplementation was effective in limiting cecum size enlargement and colonic inflammation caused by vancomycin. However, for amoxicillin and ciprofloxacin, the relative abundances of proinflammatory species were not greatly affected, and consequently, the effect of probiotic supplementation on community structure, cecum weight, and expression of inflammation-related genes was comparatively negligible. These results indicate that probiotic supplementation is effective, but only when antibiotics cause proinflammatory species-induced gut inflammation, suggesting that the necessity of probiotic supplementation is strongly influenced by the type of disturbance introduced to the community.}, }
@article {pmid32620839, year = {2020}, author = {Xiao, Y and Angulo, MT and Lao, S and Weiss, ST and Liu, YY}, title = {An ecological framework to understand the efficacy of fecal microbiota transplantation.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {3329}, pmid = {32620839}, issn = {2041-1723}, support = {U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Clostridioides difficile/physiology ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Mice ; Models, Theoretical ; Recurrence ; Treatment Outcome ; }, abstract = {Human gut microbiota plays critical roles in physiology and disease. Our understanding of ecological principles that govern the dynamics and resilience of this highly complex ecosystem remains rudimentary. This knowledge gap becomes more problematic as new approaches to modifying this ecosystem, such as fecal microbiota transplantation (FMT), are being developed as therapeutic interventions. Here we present an ecological framework to understand the efficacy of FMT in treating conditions associated with a disrupted gut microbiota, using the recurrent Clostridioides difficile infection as a prototype disease. This framework predicts several key factors that determine the efficacy of FMT. Moreover, it offers an efficient algorithm for the rational design of personalized probiotic cocktails to decolonize pathogens. We analyze data from both preclinical mouse experiments and a clinical trial of FMT to validate our theoretical framework. The presented results significantly improve our understanding of the ecological principles of FMT and have a positive translational impact on the rational design of general microbiota-based therapeutics.}, }
@article {pmid32620549, year = {2020}, author = {Ianiro, G and Mullish, BH and Kelly, CR and Kassam, Z and Kuijper, EJ and Ng, SC and Iqbal, TH and Allegretti, JR and Bibbò, S and Sokol, H and Zhang, F and Fischer, M and Costello, SP and Keller, JJ and Masucci, L and van Prehn, J and Quaranta, G and Quraishi, MN and Segal, J and Kao, D and Satokari, R and Sanguinetti, M and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.}, journal = {Gut}, volume = {69}, number = {9}, pages = {1555-1563}, pmid = {32620549}, issn = {1468-3288}, mesh = {Betacoronavirus ; COVID-19 ; Change Management ; Clostridium Infections/microbiology/*therapy ; *Coronavirus Infections/epidemiology/prevention &amp; control ; *Donor Selection ; Fecal Microbiota Transplantation/*methods ; *Gastroenterology/organization &amp; administration/trends ; Gastrointestinal Microbiome ; Humans ; Infection Control/methods/standards ; *Pandemics/prevention &amp; control ; *Patient Selection ; *Pneumonia, Viral/epidemiology/prevention &amp; control ; Risk Adjustment/methods/standards ; SARS-CoV-2 ; }, abstract = {The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.}, }
@article {pmid32620285, year = {2020}, author = {Reuter, B and Bajaj, JS}, title = {Microbiome: Emerging Concepts in Patients with Chronic Liver Disease.}, journal = {Clinics in liver disease}, volume = {24}, number = {3}, pages = {493-520}, doi = {10.1016/j.cld.2020.04.006}, pmid = {32620285}, issn = {1557-8224}, mesh = {Anti-Bacterial Agents/pharmacology/*therapeutic use ; Carcinoma, Hepatocellular/microbiology ; Chronic Disease ; Dysbiosis/*complications/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Hepatic Encephalopathy/microbiology ; Humans ; Liver Cirrhosis/complications ; Liver Diseases/complications/*microbiology ; Liver Neoplasms/microbiology ; Prebiotics ; }, abstract = {The gut microbiome is an exciting new area of research in chronic liver disease. It has shown promise in expanding our understanding of these complicated disease processes and has opened up new treatment modalities. The aim of this review is to increase understanding of the microbiome and explain the collection and analysis process in the context of liver disease. It also looks at our current understanding of the role of the microbiome in the wide spectrum of chronic liver diseases and how it is being used in current therapies and treatments.}, }
@article {pmid32618725, year = {2020}, author = {Claytor, JD and El-Nachef, N}, title = {Fecal microbial transplant for inflammatory bowel disease.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {23}, number = {5}, pages = {355-360}, doi = {10.1097/MCO.0000000000000676}, pmid = {32618725}, issn = {1473-6519}, mesh = {Colitis, Ulcerative/microbiology/therapy ; Crohn Disease/microbiology/therapy ; Dysbiosis/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: The purpose of this brief review is to investigate the current utility of fecal microbial transplantation (FMT) to ameliorate dysbiosis contributing to inflammatory bowel disease pathogenesis.<br><br>RECENT FINDINGS: Increasing data from randomized, controlled trials support a role for multiple FMT administrations in the induction of remission and even as a maintenance therapy in mild-to-moderate Ulcerative Colitis. Small series and one small randomized controlled trial among patients with Crohn's Disease and with pouchitis continue to produce conflicting clinical results and microbial profile data on the host and donor levels. It is not clear whether patients with Crohn's disease are more susceptible to disease flare after FMT. Novel FMT delivery systems, including oral, and early-intensity colonoscopic devices, are under investigation.<br><br>SUMMARY: The allure of minimizing the risks and cost of long-term immunosuppression via modulation of patient microbiota remains enticing, and the most recent randomized controlled data in ulcerative colitis reveals acceptable clinical remission rates. However, prior to wide adoption of FMT within the inflammatory bowel disease treatment armamentarium, large clinical trials identifying biomarkers of treatment success, ensuring safety across all indications, and cultivating optimized donor and host selection are needed.}, }
@article {pmid32618715, year = {2020}, author = {Wong, D and Nanda, N}, title = {Clostridium difficile disease in solid organ transplant recipients: a recommended treatment paradigm.}, journal = {Current opinion in organ transplantation}, volume = {25}, number = {4}, pages = {357-363}, pmid = {32618715}, issn = {1531-7013}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Broadly Neutralizing Antibodies/therapeutic use ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/drug therapy/*epidemiology/*therapy ; Fecal Microbiota Transplantation ; Humans ; Incidence ; Organ Transplantation/*methods/*statistics &amp; numerical data ; Randomized Controlled Trials as Topic ; Transplant Recipients/statistics &amp; numerical data ; }, abstract = {PURPOSE OF REVIEW: Organ transplant recipients have an increased incidence of Clostridium difficile disease and lower clinical response rates compared with the general population. Transplant specific treatment approaches are not defined. Therefore, a review of therapeutics in the transplant population is needed.<br><br>RECENT FINDINGS: A literature review on the current therapies for C. difficile was performed focusing on the evidence in transplant recipients and immunosuppressed populations.<br><br>SUMMARY: Transplant patients warrant an aggressive approach to treatment. The authors propose a suggested treatment paradigm for therapy.}, }
@article {pmid32618656, year = {2020}, author = {Craven, L and Rahman, A and Nair Parvathy, S and Beaton, M and Silverman, J and Qumosani, K and Hramiak, I and Hegele, R and Joy, T and Meddings, J and Urquhart, B and Harvie, R and McKenzie, C and Summers, K and Reid, G and Burton, JP and Silverman, M}, title = {Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {7}, pages = {1055-1065}, doi = {10.14309/ajg.0000000000000661}, pmid = {32618656}, issn = {1572-0241}, mesh = {Double-Blind Method ; Duodenoscopy ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; *Intestine, Small ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*therapy ; Permeability ; }, abstract = {INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability.<br><br>METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT.<br><br>RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT.<br><br>DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.}, }
@article {pmid32618640, year = {2020}, author = {Khanna, S and Pardi, D}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile infection: The COVID-19 Era.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {7}, pages = {971-974}, pmid = {32618640}, issn = {1572-0241}, mesh = {Anti-Bacterial Agents/therapeutic use ; Biological Specimen Banks/standards ; COVID-19 ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/diagnosis/microbiology/*therapy ; *Coronavirus Infections/diagnosis ; Donor Selection ; *Fecal Microbiota Transplantation ; Humans ; Mass Screening ; *Pandemics ; *Pneumonia, Viral/diagnosis ; Recurrence ; }, }
@article {pmid32617914, year = {2020}, author = {Floyd, JL and Grant, MB}, title = {The Gut-Eye Axis: Lessons Learned from Murine Models.}, journal = {Ophthalmology and therapy}, volume = {9}, number = {3}, pages = {499-513}, pmid = {32617914}, issn = {2193-8245}, support = {R01EY028858/NH/NIH HHS/United States ; R01 EY012601/EY/NEI NIH HHS/United States ; P30 DK079626/DK/NIDDK NIH HHS/United States ; T32 HL105349/HL/NHLBI NIH HHS/United States ; R01 EY025383/EY/NEI NIH HHS/United States ; R01EY028037/NH/NIH HHS/United States ; R01EY025383/NH/NIH HHS/United States ; R01EY012601/NH/NIH HHS/United States ; R01 EY028037/EY/NEI NIH HHS/United States ; R01 EY028858/EY/NEI NIH HHS/United States ; }, abstract = {A healthy gut microbiota is essential in maintaining the human body in a homeostatic state by its functions in digestion and immune tolerance. Under states of aberrant microbial composition or function (dysbiosis), the gut microbiota induces systemic inflammation that can lead to the onset of many diseases. In this review, we describe some evidence, largely from rodent studies, that supports the possible role of a dysbiotic gut microbiota in the onset and exacerbation of ocular diseases, primarily diabetic retinopathy, age-related macular degeneration, choroidal neovascularization, and uveitis. Furthermore, we examine several potential therapeutic measures that show promise in restoring the gut microbiota to a eubiotic state, preventing the aforementioned disease pathologies.}, }
@article {pmid32615390, year = {2020}, author = {Kaakoush, NO}, title = {Fecal transplants as a microbiome-based therapeutic.}, journal = {Current opinion in microbiology}, volume = {56}, number = {}, pages = {16-23}, doi = {10.1016/j.mib.2020.05.008}, pmid = {32615390}, issn = {1879-0364}, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification ; Bacterial Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Fungi/classification/genetics/isolation &amp; purification ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Impaired microbiome diversity and composition can develop into a potent etiological agent of disease and increase susceptibility to infection. Given this, interventions targeting the microbiome have developed rapidly, with healthy donor feces being a de facto source of beneficial communities employed to rebalance patients' microbiomes. Recent evidence has demonstrated that bacterial and viral richness, short chain fatty acid production, bile acid conversion as well as presence of bacterial and fungal pathobionts are associated with therapy efficacy; however, little is known of the influence of host factors such as genetics, medications, and diet. Here, current knowledge on factors associated with fecal transplant efficacy, as well as efforts to transition to other forms of therapy are reviewed.}, }
@article {pmid32614856, year = {2020}, author = {Phoba, MF and Barbé, B and Ley, B and Van Puyvelde, S and Post, A and Mattheus, W and Deborggraeve, S and Lunguya, O and Jacobs, J}, title = {High genetic similarity between non-typhoidal Salmonella isolated from paired blood and stool samples of children in the Democratic Republic of the Congo.}, journal = {PLoS neglected tropical diseases}, volume = {14}, number = {7}, pages = {e0008377}, pmid = {32614856}, issn = {1935-2735}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adolescent ; Bacteremia/*microbiology ; Child ; Child, Preschool ; Cross-Sectional Studies ; Feces/*microbiology ; Humans ; Infant ; Polymorphism, Single Nucleotide ; Salmonella/classification/*genetics ; }, abstract = {BACKGROUND: Non-typhoidal Salmonella (NTS) serotypes Typhimurium and Enteritidis are a major cause of bloodstream infections in children in sub-Saharan Africa but their reservoir is unknown. We compared pairs of NTS blood and stool isolates (with the same NTS serotype recovered in the same patient) for genetic similarity.<br><br>METHODS: Between November 2013 and April 2017, hospital-admitted children (29 days to 14 years) with culture-confirmed NTS bloodstream infections were enrolled in a cross-sectional study at Kisantu Hospital, DR Congo. Stool cultures for Salmonella were performed on a subset of enrolled children, as well as on a control group of non-febrile hospital-admitted children. Pairs of blood and stool NTS isolates were assessed for genetic similarity by multiple-locus variable-number of tandem repeats (MLVA) and genomics analysis.<br><br>RESULTS: A total of 299 children with NTS grown from blood cultures (Typhimurium 68.6%, Enteritidis 30.4%, other NTS 1.0%) had a stool sample processed; in 105 (35.1%) of them NTS was detected (Typhimurium 70.5%, Enteritidis 25.7%, other NTS 3.8%). A total of 87/105 (82.9%) pairs of blood and stool NTS isolates were observed (representing 29.1% of the 299 children). Among 1598 controls, the proportion of NTS stool excretion was 2.1% (p < 0.0001). MLVA types among paired isolates were identical in 82/87 (94.3%) pairs (27.4% of the 299 children; 61/66 (92.4%) in Typhimurium and 21/21 (100%) in Enteritidis pairs). Genomics analysis confirmed high genetic similarity within 41/43 (95.3%) pairs, showing a median SNP difference of 1 (range 0-77) and 1 (range 0-4) for Typhimurium and Enteritidis pairs respectively. Typhimurium and Enteritidis isolates belonged to sequence types ST313 lineage II and ST11 respectively.<br><br>CONCLUSION: Nearly 30% of children with NTS bloodstream infection showed stool excretion of an NTS isolate with high genetic similarity, adding to the evidence of humans as a potential reservoir for NTS.}, }
@article {pmid32611702, year = {2020}, author = {Woodworth, MH}, title = {mSphere of Influence: Microbiome-Associated Phenotypes Are Modifiable.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32611702}, issn = {2379-5042}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Child ; Clinical Trials as Topic ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Malawi ; Mice ; Mice, Inbred C57BL ; *Phenotype ; Twins ; }, abstract = {Michael Woodworth focuses on translational microbiome therapeutic research. In this mSphere of Influence article, he reflects on how "Gut microbiomes of Malawian twin pairs discordant for kwashiorkor" by Michelle Smith et al. (M. I. Smith, T. Yatsunenko, M. J. Manary, I. Trehan, et al., Science 339:548-554, 2013, https://doi.org/10.1126/science.1229000) made an impact on him by revealing the causal influence of microbial communities in the development of severe malnutrition.}, }
@article {pmid32610522, year = {2020}, author = {Bilinski, J and Dziurzynski, M and Grzesiowski, P and Podsiadly, E and Stelmaszczyk-Emmel, A and Dzieciatkowski, T and Dziewit, L and Basak, GW}, title = {Multimodal Approach to Assessment of Fecal Microbiota Donors based on Three Complementary Methods.}, journal = {Journal of clinical medicine}, volume = {9}, number = {7}, pages = {}, pmid = {32610522}, issn = {2077-0383}, support = {1WP/FS200/ZW2/17//Ministerstwo Nauki i Szkolnictwa Wy&#x17c;szego/ ; }, abstract = {Methods of stool assessment are mostly focused on next-generation sequencing (NGS) or classical culturing, but only rarely both. We conducted a series of experiments using a multi-method approach to trace the stability of gut microbiota in various donors over time, to find the best method for the proper selection of fecal donors and to find "super-donor" indicators. Ten consecutive stools donated by each of three donors were used for the experiments (30 stools in total). The experiments assessed bacterial viability measured by flow cytometry, stool culturing on different media and in various conditions, and NGS (90 samples in total). There were no statistically significant differences between live and dead cell numbers; however, we found a group of cells classified as not-dead-not-alive, which may be possibly important in selection of "good" donors. Donor C, being a regular stool donor, was characterized by the largest number of cultivable species (64). Cultivable core microbiota (shared by all donors) was composed of only 16 species. ANCOM analysis of NGS data highlighted particular genera to be more abundant in one donor vs. the others. There was a correlation between the not-dead-not-alive group found in flow cytometry and Anaeroplasma found by NGS, and we could distinguish a regular stool donor from the others. In this work, we showed that combining various methods of microbiota assessment gives more information than each method separately.}, }
@article {pmid32607098, year = {2020}, author = {Park, R and Umar, S and Kasi, A}, title = {Immunotherapy in Colorectal Cancer: Potential of Fecal Transplant and Microbiota-augmented Clinical Trials.}, journal = {Current colorectal cancer reports}, volume = {16}, number = {4}, pages = {81-88}, pmid = {32607098}, issn = {1556-3790}, support = {R01 CA185322/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: This review summarizes the role of the microbiome in colorectal cancer (CRC) in the setting of immunotherapy and emphasizes the potential of microbiota-influencing strategies with a focus on the use of fecal microbiota transplant (FMT).<br><br>RECENT FINDINGS: Observations from preclinical and clinical studies suggest that the human gut microbiome is implicated in the CRC carcinogenesis and is integral in determining the clinical response and toxicity to immunotherapy. Among the therapeutic methods devised to exploit the microbiome, FMT is the most direct method and is backed by the highest level of evidence of efficacy in nonneoplastic disease settings. Furthermore, a favorable microbiome has the potential to overcome immunotherapy resistance and ameliorate immune-related adverse events (irAEs). To this end, clinical trials are underway to evaluate the potential of FMT and microbiota-augmented methods in the setting of immunotherapy in CRC.<br><br>SUMMARY: Evidence from animal studies, retrospective studies, and smaller-scale prospective human studies have led to initiation of a number of microbiota-augmented clinical trials in CRC. Given the intimate relationship between the gut microbiota and the immune system as well as antitumor immune responses, potentiating immunotherapy and managing its toxicity are major areas of research in microbiota-augmented therapies in cancer. Therefore, evaluation of the patient microbiome as a routine part of clinical outcome analysis is warranted in future clinical trials.}, }
@article {pmid32605650, year = {2020}, author = {Benech, N and Sokol, H}, title = {Fecal microbiota transplantation in gastrointestinal disorders: time for precision medicine.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {58}, pmid = {32605650}, issn = {1756-994X}, mesh = {*Fecal Microbiota Transplantation ; Gastrointestinal Diseases/*therapy ; Humans ; *Precision Medicine ; }, abstract = {Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating inflammatory bowel diseases and irritable bowel syndrome in an increasing number of randomized controlled trials. Recently published data gives striking insights into the factors associated with FMT success paving the road for the use of precision medicine in gastrointestinal disorders.}, }
@article {pmid32601752, year = {2020}, author = {Meyer, DC and Hill, SS and Bebinger, DM and McDade, JA and Davids, JS and Alavi, K and Maykel, JA}, title = {Resolution of multiply recurrent and multifocal diverticulitis after fecal microbiota transplantation.}, journal = {Techniques in coloproctology}, volume = {24}, number = {9}, pages = {971-975}, pmid = {32601752}, issn = {1128-045X}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; *Diverticulitis ; Fecal Microbiota Transplantation ; Feces ; Female ; Humans ; Middle Aged ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: The exact pathophysiology of diverticulitis is not well understood and may be multifactorial. Recent studies highlight dysbiosis as a plausible mechanism. FMT is a safe strategy to restore commensal colon microbiota and has proven to be an effective treatment for gastrointestinal dysbiosis such as Clostridium difficile infection (CDI). There have been no studies reporting the treatment of diverticulitis with FMT. Our aim was to describe the novel application of fecal microbiota transplantation (FMT) for the treatment of recurrent diverticulitis.<br><br>CASE: We report a case of a 63-year-old woman who had a 13-year history of multiply recurrent and multifocal diverticulitis previously treated with numerous short courses of intravenous and oral antibiotics for acute flares, two segmental colon resections, and suppressive antibiotic therapy for recurrent disease. Secondary to multiple courses of antibiotics , the patient developed CDI. She was treated with a single round of FMT and subsequently stopped all antibiotics at the time of FMT.<br><br>RESULTS: In 20 months of follow-up, the patient has had no further recurrence of diverticulitis or CDI.<br><br>CONCLUSIONS: FMT could prove to be a novel therapy for refractory diverticulitis but requires further investigation.}, }
@article {pmid32601270, year = {2020}, author = {Fremin, BJ and Sberro, H and Bhatt, AS}, title = {MetaRibo-Seq measures translation in microbiomes.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {3268}, pmid = {32601270}, issn = {2041-1723}, support = {P30 AG066515/AG/NIA NIH HHS/United States ; P50 AG047366/AG/NIA NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; U24 AG021886/AG/NIA NIH HHS/United States ; }, mesh = {Metagenomics ; Microbiota/*genetics ; Protein Biosynthesis/genetics ; RNA-Seq/*methods ; }, abstract = {No method exists to measure large-scale translation of genes in uncultured organisms in microbiomes. To overcome this limitation, we develop MetaRibo-Seq, a method for simultaneous ribosome profiling of tens to hundreds of organisms in microbiome samples. MetaRibo-Seq was benchmarked against gold-standard Ribo-Seq in a mock microbial community and applied to five different human fecal samples. Unlike RNA-Seq, Ribo-Seq signal of a predicted gene suggests it encodes a translated protein. We demonstrate two applications of this technique: First, MetaRibo-Seq identifies small genes, whose identification until now has been challenging. For example, MetaRibo-Seq identifies 2,091 translated, previously unannotated small protein families from five fecal samples, more than doubling the number of small proteins predicted to exist in this niche. Second, the combined application of RNA-Seq and MetaRibo-Seq identifies differences in the translation of transcripts. In summary, MetaRibo-Seq enables comprehensive translational profiling in microbiomes and identifies previously unannotated small proteins.}, }
@article {pmid32600151, year = {2020}, author = {Hazan, S}, title = {Rapid improvement in Alzheimer's disease symptoms following fecal microbiota transplantation: a case report.}, journal = {The Journal of international medical research}, volume = {48}, number = {6}, pages = {300060520925930}, pmid = {32600151}, issn = {1473-2300}, mesh = {Aged ; Aged, 80 and over ; *Alzheimer Disease/therapy ; Brain ; *Cognitive Dysfunction/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Alzheimer's disease (AD), the most common form of dementia, is a leading cause of death and a major cause of morbidity in older people. The disease is characterized by progressive memory loss, cognitive impairment, and the cerebral accumulation of amyloid-β peptide. Given the health and economic impacts of AD, treatments that target the underlying etiology of AD or modify the course of the disease are of significant interest. The gut microbiome has been increasingly implicated in the pathogenesis of several neurological diseases, including multiple sclerosis and Parkinson's disease. Furthermore, emerging evidence has demonstrated that there are alterations in gut microbiome composition in patients with AD, suggesting involvement of the microbiome-gut-brain axis. We present symptom improvement in a patient with AD following fecal microbiota transplantation for a Clostridioides difficile infection.}, }
@article {pmid32594732, year = {2020}, author = {Chen, QY and Tian, HL and Yang, B and Qin, HL and Li, N}, title = {[A case report of refractory methemoglobinemia after nitrite poisoning treated by fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {90-92}, doi = {10.3760/cma.j.cn.441530-20200416-00218}, pmid = {32594732}, issn = {1671-0274}, mesh = {Fecal Microbiota Transplantation/*methods ; Humans ; Methemoglobinemia/*chemically induced/*therapy ; Nitrites/*poisoning ; }, }
@article {pmid32594731, year = {2020}, author = {Yang, B and Chen, QY and Tian, HL and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Application of modified blind nasojejunal tube technique in fecal microbiota transplantation - report of 2267 cases].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {86-89}, doi = {10.3760/cma.j.cn.441530-20200414-00209}, pmid = {32594731}, issn = {1671-0274}, mesh = {Enteral Nutrition ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Humans ; Intubation, Gastrointestinal/*methods ; Jejunum ; Treatment Outcome ; }, }
@article {pmid32594729, year = {2020}, author = {Chen, QY and Yang, B and Tian, HL and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Association between the clinical efficacy of fecal microbiota transplantation in recipients and the choice of donor].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {69-76}, doi = {10.3760/cma.j.cn.441530-20200417-00222}, pmid = {32594729}, issn = {1671-0274}, support = {81670493//National Natural Science Fundation of China/ ; }, mesh = {Autistic Disorder/*therapy ; Butyrates/analysis ; Case-Control Studies ; *Donor Selection ; Fatty Acids, Volatile/analysis ; Fecal Microbiota Transplantation/*methods ; Feces/chemistry/microbiology ; Humans ; Intestinal Diseases/*therapy ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Objective: To examine the association between the clinical efficacy of fecal microbiota transplantation (FMT) in recipients and the choice of donor, and to observe the characteristics of intestinal flora and metabolites among different donors. Methods: A retrospective case-control study was conducted. Donor whose feces was administrated for more than 30 recipients was enrolled. Data of 20 FMT donors and corresponding recipients at Intestinal Microecology Diagnosis and Treatment Center of the Tenth People's Hospital from October 2018 to December 2019 were collected retrospectively. During follow-up, the efficacy of each recipient 8-week after FMT treatment was recorded and analyzed. Based on the efficacy of each donor, the donors were divided into three groups: high efficacy group (effective rate >60%, 10 donors), moderate efficacy group (effective rate 30%-60%, 6 donors) and low efficacy group (effective rate <30%, 4 donors). The structure of the bacterial flora and the content of fecal short-chain fatty acids in each group of donors were detected and compared among groups. Association of the efficacy of each donor group with the morbidity of complications, and association of efficacy of recipients with donors were analyzed. The evaluation indicators of FMT efficacy included objective clinical effectiveness and/or subjective effectiveness. Objective effectiveness indicated clinical cure plus clinical improvement, and subjective effectiveness indicated marked effectiveness plus medium effectiveness through questionnaire during follow-up. Results: A total of 1387 recipients were treated by 20 donors, including 749 cases of chronic constipation, 141 cases of chronic diarrhea, 107 cases of inflammatory bowel disease (IBD), 121 cases of irritable bowel syndrome (IBS), 83 cases of autism, and 186 cases of other diseases, such as radiation bowel injury, intestinal pseudo-obstruction, paralytic intestinal obstruction, functional bloating and allergic diseases. There were 829 cases, 403 cases, and 155 cases in high efficacy group, moderate efficacy group and low efficacy group respectively. Baseline data among 3 groups were not significantly different (all P> 0.05). In comparison of bacterial abundance (operational taxonomic unit, OTU) among different effective donor groups, the high efficacy group was the highest (330.68±57.28), the moderate efficacy group was the second (237.79±41.89), and the low efficacy group was the lowest (160.60±49.61), whose difference was statistically significant (F=16.910, P<0.001). In comparison of bacterial diversity (Shannon index), the high efficacy group and the moderate efficacy group were higher (2.96±0.36 and 2.67±0.54, respectively), and the low efficacy group was lower (2.09±0.55), whose difference was statistically significant (F=5.255, P=0.017). In comparison of butyric acid content among three groups, the high efficacy group had the highest [(59.20±9.00) μmol/g], followed by middle efficacy group [(46.92±9.48) μmol/g], and the low efficacy group had the lowest [(37.23±5.03) μmol/g], whose difference was statistically significant (F=10.383, P=0.001). The differences of acetic acid and propionic acid among three groups were not statistically significant (all P>0.05). A total of 418 cases developed complications (30.1%). Morbidity of complication in low efficacy group, moderate efficacy group and high efficacy group was 40.6% (63/155), 30.0% (121/403) and 28.2% (243/829) respectively, and the difference was statistically significant (χ(2)=9.568, P=0.008). The incidence of diarrhea in low efficacy group, moderate efficacy group and high efficacy group was 7.1% (11/155), 4.0% (16/403) and 2.8% (23/829) respectively, and the difference was statistically significant (χ(2)=7.239, P=0.027). Comparing the incidences of other types of complications, no statistically significant differences were found (all P>0.05). Follow up began 8 weeks after the FMT treatment. The total follow-up rate was 83.6% (1160/1387). The overall effective rate 58.3% (676/1160). Effective rates of various diseases were as follows: chronic constipation 54.3% (328/604), chronic diarrhea 88.5% (115/130), IBD 56.1% (55/98), IBS 55.1% (59/107), autism 61.6% (45/73), and other diseases 50.0% (74/148). Comparing the effective rate of three groups of donors for different diseases, there was no statistically significant difference in chronic diarrhea (P>0.05); there was a positive correlation trend in IBD, IBS and autism, but the differences were not statistically significant (all P>0.05). For chronic constipation and other diseases, high efficacy group had the highest effective rate [65.0% (243/374) and 63.2% (55/87)], followed by moderate efficacy group [49.4% (86/174) and 38.1% (16/42)], and low efficacy group had the lowest [16.1% (9/56) and 15.8% (3/19)], whose differences were significant (all P<0.05). Conclusions: Different donors have different efficacy in different diseases. Chronic constipation, radiation bowel injury, etc. need to choose donors with high efficacy. IBD, IBS and autism may also be related to the effectiveness of donors, while chronic diarrhea is not associated to the donor. The efficiency of the donor is negatively correlated to the morbidity of complications. The abundance and diversity of intestinal flora and the content of butyric acid may affect the efficacy of the donor.}, }
@article {pmid32594728, year = {2020}, author = {Tian, HL and Chen, QY and Yang, B and Ma, CL and Lin, ZL and Zhang, XY and Zhou, SL and Qin, HL and Li, N}, title = {[Effects of fecal microbiota transplantation in different routes on the clinical efficacy of slow transit constipation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {63-68}, doi = {10.3760/cma.j.cn.441530-20200415-00212}, pmid = {32594728}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; 04.99.18001//Special fund for the construction of the clinical center of Tenth People's Hospital of Tongji University/ ; }, mesh = {Adult ; Constipation/physiopathology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Transit/*physiology ; Humans ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Objective: To evaluate the efficacy and safety of the fecal microbiota transplantation (FMT) in the different route administration for slow transit constipation (STC). Methods: A retrospective cohort study was conducted. The clinical data of 270 STC patients who voluntarily received FMT treatment in the Tenth People's Hospital of Tongji University from May 2018 to May 2019 were collected. Non-relative healthy adult standard donors were applied. The treatment routes of bacterial flora transplantation included nasojejunal tube (nasal enteral tube group, 120 cases), oral enterobacterial capsule treatment (oral capsule group, 120 cases), and colonoscopy infusion (colonoscopy group, 30 cases). The efficacy and safety of treatment among the three groups were compared. Results: Transplanted bacteria of three groups were extracted from 100 g of fresh feces. All the patients successfully completed the transplantation. The waiting time for the nasal enteral tube group, oral capsule group and colonoscopy group was (1.5±0.5) d, (0.4±0.3) d and (3.6±0.8) d respectively; the cost of establishing the transplantation path was (495±20) yuan, (25±10) yuan and (1420±45) yuan respectively, whose differences were statistically significant (F=9.210, P=0.03; F=10.600,P=0.01). The clinical improvement rates at 1 month after FMT treatment in the nasojejunal tube group, oral capsule group and colonoscopy group were 74.2% (89/120), 60.0% (72/120) and 53.3% (16/30) respectively, whose difference was statistically significant (χ(2)=5.990, P<0.05). The clinical improvement rates at 3 months after treatment were 71.1% (69/97), 53.6% (45/84), and 44.0% (11/25) respectively, whose difference was statistically significant (χ(2)=7.620, P<0.05). The incidence of adverse reactions in the colonoscopy group was 76.7% (23/30), which was higher than that in the nasal nasojejunal group (39.2%, 47/120) and oral capsule group (21.7%, 26/120). The most common adverse reactions in the nasojejunal tube group, oral capsule group and colonoscopy group were respiratory discomfort (17.5%, 21/120), nausea and vomiting (10.0%, 12/120), and diarrhea (36.7%, 11/30). During the 3-month follow-up after treatment, no FMT-related adverse reactions were reported. Conclusions: The nasojejunal tube route has stable clinical efficacy and operability, while the oral capsule route has shorter waiting time and less cost. However, the adverse reactions caused by different transplantation methods are different, thus personalized transplantation method should be recommended.}, }
@article {pmid32594727, year = {2020}, author = {Lin, ZL and Chen, QY and Tian, HL and Yang, B and Zhao, D and Ye, C and Zhang, XY and Ma, CL and Qin, HL and Li, N}, title = {[Effect of fecal bacterial preservation time on the outcomes of fecal microbiota transplantation for slow transit constipation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {56-62}, doi = {10.3760/cma.j.cn.441530-20200414-00207}, pmid = {32594727}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; 04.99.18001//Special Fund for the Construction of the Clinical Center of Tenth People's Hospital of Tongji University/ ; }, mesh = {Constipation/physiopathology/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Transit/*physiology ; Humans ; Quality of Life ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {Objective: To investigate the effect of different fecal bacterial preservation time on the efficacy and complications of FMT. Methods: A retrospective cohort study was carried out. Clinical data of 483 patients with slow transit constipation undergoing voluntary FMT at Intestinal Microecology Diagnosis and Treatment Center from August 2017 to October 2019 were retrospectively collected. According to the storage time of fecal bacterial samples used in FMT treatment, the cases were divided into fresh bacterial solution (n=29), bacterial solution stored at -80℃ for 1 week (n=187), 1 month (n=121), 3 months (n=89), 6 months (n=38), and 12 months (n=19). The total number of complete bowel movement, Wexner constipation score, gastrointestinal quality of life index (GIQLI), FMT satisfaction score and related adverse reactions were summarized and compared among groups 1 week and 1 month after FMT treatment. Results: There were no statistically significant differences in the baseline data of patients among different bacterial solution storage time (all P>0.05). After 1 month of treatment, the overall frequency of defecation of all the patients was (3.83 ± 1.22) times/week, Wexner constipation score was (6.74 ± 3.56) points, GIQLI score was (108.76 ± 15.38) points, clinical cure rate was 57.8% (279/483). The improvement rate was 66.3% (320/483), and the treatment satisfaction was (3.85 ± 0.93) points. No severe FMT-associated complication and death were observed during treatment and follow-up period. FMT-related adverse events occurred in 115 cases (23.8%), including nausea in 25 cases (5.2%), vomiting in 13 (2.7%), diarrhea in 21 (4.3%), abdominal pain in 16 (3.3%), abdominal distension in 33 (6.8%), sore throat in 56 (11.6%) and fever in 16(3.3%), all of which relieved after symptomatic treatment. There were no statistically significant differences in the number of defecations, Wexner constipation scores, and GIQLI scores before FMT, 1 week and 1 month after FMT treatment among different bacterial solution storage groups (all P>0.05). Differences of clinical cure rate, clinical improvement rate, and treatment satisfaction of patients 1 week and 1 month after treatment were not statistically significant (all P>0.05). Among the groups, differences in the overall complications and types of complications after FMT treatment were not statistically significant (all P>0.05). Conclusions: FMT is safe and effective in the treatment of slow transit constipation. Fresh fecal bacterial samples or fecal bacterial samples frozen at -80℃ for 1 year can be safely applied to FMT for the treatment of slow transit constipation, with stable short-term efficacy and without serious adverse reactions.}, }
@article {pmid32594726, year = {2020}, author = {Chen, QY and Tian, HL and Yang, B and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Effect of intestinal preparation on the efficacy and safety of fecal microbiota transplantation treatment].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {48-55}, doi = {10.3760/cma.j.cn.441530-20200418-00225}, pmid = {32594726}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Anti-Bacterial Agents/administration &amp; dosage ; Autistic Disorder/*therapy ; Cathartics/administration &amp; dosage ; Enema ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Humans ; Intestinal Diseases/*therapy ; Male ; Middle Aged ; Preoperative Care/methods ; Recurrence ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {Objective: To investigate the effect of intestinal preparation on the efficacy and complications of fecal microbiota transplantation (FMT). Methods: A retrospective cohort study was performed. Clinical and follow-up data of 1501 patients who received FMT in the department of Colorectal Disease Specialty, Intestinal Microecology Diagnosis and Treatment Center, the Tenth People's Hospital, Tongji University from February 2018 to June 2019 were collected retrospectively. According to the intestinal preparation before FMT treatment, patients were divided into non-intestinal preparation group (n=216), antibiotic pretreatment group (n=383), intestinal cleansing group (n=267), and antibiotic combined with intestinal cleansing group (n=635). The adverse reactions after FMT treatment and the effective rates at 4-week and 8-week after treatment among the groups were compared. Patients, who repeated FMT treatment in the 3rd month and the 6th month due to reduced efficacy or ineffectiveness were divided into two subgroups: without intestinal preparation group and with intestinal preparation group. The effective rates of the two subgroups were compared. Results: Of the 1501 cases, 588 were male and 913 were female with mean age of (43.3±13.7) years and body mass index of (20.2±2.1) kg/m(2). Transplantation course was (3.3±1.7) weeks. The underlying diseases mainly included constipation (n=564), Crohn's disease (n=157), ulcerative colitis (n=142), irritable bowel syndrome (n=158), recurrent C. difficile infection (CDI) (n=106), autism (n=84), radiation intestinal injury (n=133), radiation enteritis (n=133), and non-CDI chronic diarrhea (n=60); the remaining cases (n=155). Baseline data among the 4 groups were not significantly different (all P>0.05). The overall morbidity of complication was 31.1% (467/1501), including 41 cases of vomiting (2.7%), 91 of nausea (6.1%), 49 of diarrhea (3.3%), 41 of abdominal pain (2.7%), 79 of bloating (5.3%), 72 of throat pain (4.8%), 38 of dizziness (2.5%), 51 of fever (3.4%), 3 of pulmonary infection (0.2%) and 2 of intestinal infection (0.1%). The above symptoms disappeared after symptomatic treatment. There was no statistically significant difference in the incidence of adverse reactions among the 4 groups (P>0.05). After 4-week of FMT treatment, the overall effective rate was 63.5% (902/1420); the effective rate of non-intestinal preparation group, antibiotic pretreatment group, intestinal cleaning group, and antibiotic combined with intestinal cleansing groupwas 57.6% (114/198), 64.2% (231/360), 60.2% (154/265) and 66.5% (403/606), respectively, with no statistically significant difference (χ(2)=6.659, P=0.084). After 8-week of FMT treatment, the overall effective rate was 61.3% (729/1293); the effective rate of non-intestinal preparation group, antibiotic pretreatment group, intestinal cleaning group, and antibiotic combined with intestinal cleansing group was 54.0% (88/163), 62.2% (202/325), 57.4% (132/230) and 64.4% (370/575), respectively, with no statistically significant difference (χ(2)=13.620, P=0.003). The effective rates of antibiotic combined with intestinal cleansing group and antibiotic pretreatment group were obviously higher than that of non-intestinal preparation group (χ(2)=5.789, P=0.016; χ(2)=10.117, P=0.001). Subgroup analysis showed that in the third month, the effective rate at 4-week after treatment was 60.1% (184/306) in the without intestinal preparation group and 61.5% (115/187) in the with intestinal preparation group, whose difference was not significant (χ(2)=0.091, P=0.763); however, in the sixth month, the effective rate at 4-week after treatment was 51.4% (89/173) in the without intestinal preparation group and 61.2% (161/263) in the with intestinal preparationgroup, whose difference was significant (χ(2)=4.229, P=0.040). Conclusions: FMT treatment is safe and effective. The combination of antibiotics and intestinal cleaning can improve overall efficacy of FMT. For patients who need repeated FMT treatment, the combination of antibiotics and intestinal cleaning program within 3 months has no significant effect on the effective rate, but in the sixth month, combinedpreparation is necessary.}, }
@article {pmid32594725, year = {2020}, author = {Zhang, FM and Liu, YF}, title = {[Evidence and decision of the choice of delivery way in washed microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {45-47}, doi = {10.3760/cma.j.cn.441530-20200507-00259}, pmid = {32594725}, issn = {1671-0274}, mesh = {Enema ; Enteral Nutrition ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Humans ; Intubation, Gastrointestinal ; }, abstract = {Washed microbiota transplantation (WMT) is a new concept and technique of fecal microbiota transplantation. The delivery routes of WMT include oral capsule, nasogastric tube, nasojejunal tube, gastroscopy, colonic transendoscopic enteral tubing, and anal enema. The research results among different indications or different designs based on the same indication are quite different, partially because of the influence of WMT delivery route. In the process of clinical research design and clinical practice, there are four aspects that affect the decision-making of WMT delivery route: safety, efficacy, cost-effectiveness, and patients' willingness. This article focuses on how to integrate the four aspects mentioned above in the decision-making process of choosing proper delivery of WMT for the final goal of mutual satisfaction between doctors and patients.}, }
@article {pmid32594720, year = {2020}, author = {,  and ,  and ,  and , }, title = {[Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {14-20}, doi = {10.3760/cma.j.cn.441530-20200420-00228}, pmid = {32594720}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {China ; Consensus ; Fecal Microbiota Transplantation/adverse effects/*methods/*standards ; Humans ; }, abstract = {Fecal microbiota transplantation (FMT) has gradually shown application prospects in the treatment of intestinal and extraintestinal diseases. In order to standardized FMT operation, based on the clinical experience of the Tenth People's Hospital Affiliated to Tongji University, combined with domestic and foreign literature, Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association to formulated the" Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes". It includes four parts: the selection of delivery route, the methodology of transplantation path establishment, the clinical application, and the monitoring of adverse events.}, }
@article {pmid32594719, year = {2020}, author = {,  and ,  and ,  and , }, title = {[Chinese experts consensus on standardized methodology and clinical application of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {5-13}, doi = {10.3760/cma.j.cn.441530-20200420-00231}, pmid = {32594719}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {China ; Consensus ; Fecal Microbiota Transplantation/adverse effects/*methods/*standards ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is to transplant the functional bacteria in the feces of healthy people into the patients' intestines, rebuild the new balance of intestinal flora, and achieve the treatment goals of intestinal and extraintestinal diseases. In the past 10 years, FMT has made a breakthrough in the treatment of intestinal and extraintestinal diseases, which is highly expected to treat difficult diseases. However, due to the complexity of FMT methodology and the lack of a unified standard, there is a high heterogeneity in FMT efficacy among various researches, greatly affected its clinical application. Under the initiative of Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association, the first expert consensus on standardized methodology and clinical application of FMT was established in China, with a view to improving the efficacy of FMT, reducing the incidence of adverse reactions and promoting the clinical application of FMT.}, }
@article {pmid32594718, year = {2020}, author = {Li, N}, title = {[Practice and consideration of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {1-4}, doi = {10.3760/cma.j.cn.441530-20200420-00230}, pmid = {32594718}, issn = {1671-0274}, mesh = {China ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/methods/*standards ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/*microbiology/physiology/physiopathology ; Recurrence ; Treatment Outcome ; }, abstract = {As an innovative therapy, FMT has made a breakthrough in the treatment of recurrent Clostridium difficile infection (CDI). With the rapid development of biotechnology, the relationship between intestinal microflora and diseases has been gradually eluciated. Great hope has also been given to FMT in other intestinal and extraintestinal diseases with ineffective traditional treatment. However, as a new therapy method, FMT still has many unknown fields, such as the selection of clinical donors, the preparation of standardized bacterial solution and capsule, the selection of indications, the matching of donor and receptor, and the prevention and treatment of complications. Since 2012, our center has carried out treatment research and practice of FMT, so far with more than 60 000 FMTs for more than 3500 cases. Based on large sample data and experience, this special issue reports and discusses the above topics, and focuses on the establishment and clinical application of standardized methodology of FMT, which will undoubtedly play a positive role in promoting the healthy development of FMT treatment in China.}, }
@article {pmid32593304, year = {2020}, author = {Martin, K and Taylor, A and Tam, C and Hill, P and Machet, D and Goodman, D}, title = {Colonic mucosa-associated lymphoid tissue in a renal transplant recipient: a case report.}, journal = {Journal of medical case reports}, volume = {14}, number = {1}, pages = {81}, pmid = {32593304}, issn = {1752-1947}, mesh = {Colonic Neoplasms/*diagnosis ; Helicobacter pylori/immunology ; Humans ; Immunocompromised Host ; Immunoglobulin G/blood ; Intestinal Mucosa/*pathology ; Kidney Transplantation ; Lymphoma, B-Cell, Marginal Zone/*diagnosis ; Male ; Middle Aged ; *Occult Blood ; *Transplant Recipients ; Watchful Waiting ; }, abstract = {BACKGROUND: Extra-gastric (particularly colonic) lymphoma of mucosa-associated lymphoid tissue in the immunosuppressed solid organ transplant recipient is rare. We report a case of low-volume mucosa-associated lymphoid tissue lymphoma with colonic and bone marrow involvement in a renal transplant recipient that has been managed conservatively.<br><br>CASE PRESENTATION: A 62-year-old Caucasian&#xa0;man, 14&#x2009;years after kidney transplantation, was diagnosed as having extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue with bone marrow and colonic involvement, after a colonoscopy identified mucosa-associated lymphoid tissue lymphoma in a sessile sigmoid polyp following surveillance fecal occult blood testing that returned a positive result. A gastric biopsy showed no evidence of Helicobacter pylori, but Helicobacter pylori immunoglobulin G was positive. He received Helicobacter pylori eradication treatment and is being managed expectantly. Immunosuppression was unchanged with prednisolone, mycophenolate mofetil, and cyclosporine A. Renal allograft function has remained stable.<br><br>CONCLUSIONS: This case highlights the unexpected occurrence of colonic mucosa-associated lymphoid tissue lymphoma in a kidney transplant recipient. The case emphasizes the importance of histopathological diagnosis of colonic lesions in this patient cohort because the unusual diagnosis of low-volume mucosa-associated lymphoid tissue lymphoma can be managed expectantly as it does not appear to be clinically aggressive in the immunosuppressed solid organ transplant.}, }
@article {pmid32592577, year = {2020}, author = {Jiang, S and Wang, B and Sha, T and Li, X}, title = {Changes in the Intestinal Microbiota in Patients with Stage 5 Chronic Kidney Disease on a Low-Protein Diet and the Effects of Human to Rat Fecal Microbiota Transplantation.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {26}, number = {}, pages = {e921557}, pmid = {32592577}, issn = {1643-3750}, mesh = {Adipose Tissue ; Adult ; Aged ; Animals ; Bacteroides ; Body Weight ; Cholesterol/blood ; Clostridiales ; Creatinine/blood ; *Diet, Protein-Restricted ; Escherichia ; *Fecal Microbiota Transplantation ; Female ; Firmicutes ; Gastrointestinal Microbiome/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Kidney Failure, Chronic/*microbiology ; Klebsiella ; Male ; Middle Aged ; Prevotella ; RNA, Ribosomal, 16S ; Rats ; Sequence Analysis, RNA ; Serum Albumin/metabolism ; Shigella ; Triglycerides/blood ; }, abstract = {BACKGROUND Dietary protein restriction is recommended for patients with stage 5 chronic kidney disease (CKD), or end-stage renal disease (ESRD). This study aimed to investigate the changes in the intestinal microbiota due to different dietary regimens in patients with stage 5 CKD and the effects of human to rat fecal microbiota transplantation. MATERIAL AND METHODS Second-generation high-throughput sequencing was used to analyze the amplifiers in the 16S rRNA V4 region in the intestinal microbiota of patients with stage 5 CKD and healthy individuals. The intestinal microbiota of patients with stage 5 CKD in the low-protein group and the healthy individual group was transferred by human to rat fecal microbiota transplantation using Sprague-Dawley rats. Data underwent meta-analysis using Meta-Stat. RESULTS Patients with CKD on a very low-protein diet showed an increase in intestinal Escherichia, Shigella, and Klebsiella, a decrease in Blautia, heat map analysis showed that Christensenellaceae R-7 group rs1 were significantly increased, and MetaStat analysis showed that Bacteroides, Prevotella, and Mitsuokella were significantly increased. Following human to rat fecal microbiota transplantation from patients with stage 5 CKD, the profile of the rat intestinal microbiota became similar to the human donors. The weight of the rats fed a very low-protein diet after fecal microbiota transplantation significantly decreased after six weeks compared with normal rats and rats that received normal fecal microbiota transplantation. CONCLUSIONS Patients with stage 5 CKD on a very low-protein diet showed changes in the intestinal microbiota that could be transferred from humans to rats by fecal microbiota transplantation.}, }
@article {pmid32592018, year = {2020}, author = {Meyer, R and Alcalay, M and Jamal, R and Horesh, N and Friedman, T and Nadler, R and Carter, D and Ram, E}, title = {Validation of the Wexner scale in a Hebrew-speaking population.}, journal = {International urogynecology journal}, volume = {31}, number = {12}, pages = {2583-2587}, pmid = {32592018}, issn = {1433-3023}, mesh = {*Fecal Incontinence ; Female ; Humans ; *Pelvic Floor Disorders ; Reproducibility of Results ; Surveys and Questionnaires ; Translating ; }, abstract = {INTRODUCTION: The Cleveland Clinic Incontinence Score, known as the Wexner Score (WS), is a simple, disease-specific questionnaire for anal incontinence (AI) assessment. We aimed to translate and validate a Hebrew version of the WS.<br><br>METHODS: Between November 2018 and December 2019, the WS was back translated and reviewed by a multidisciplinary pelvic floor team. The questionnaire was filled out by patients visiting the urogynecology and surgical pelvic floor clinics. Two weeks after completion, the patients were contacted using telephone surveys to assess the test-retest reliability examination. Construct validity was assessed by comparing the WS to the Colorectal-Anal Distress Inventory 8 (CRADI-8), a part of the validated Hebrew version of the Pelvic Floor Distress Inventory questionnaire (PFDI-20).<br><br>RESULTS: Overall, 91 female patients completed the WS questionnaire. Eighty-five percent (n&#x2009;=&#x2009;78) responded to the re-test WS questionnaire. A high intraclass coefficient of 0.87 was found in the WS total score, with a range from 0.82 to 0.86 for its subscales. A significant positive relationship between the Hebrew versions of the WS and CRADI-8 scores was established (r&#x2009;=&#x2009;0.66, p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSION: A new, Hebrew-translated version of the WS is a reliable and valid instrument for assessing AI.}, }
@article {pmid32588829, year = {2020}, author = {Zhgun, ES and Kislun, YV and Kalachniuk, TN and Veselovsky, VA and Urban, AS and Tikhonova, PO and Pavlenko, AV and Ilchenko, GN and Ilina, EN}, title = {[Evaluation of metabolites levels in feces of patients with inflammatory bowel diseases].}, journal = {Biomeditsinskaia khimiia}, volume = {66}, number = {3}, pages = {233-240}, doi = {10.18097/PBMC20206603233}, pmid = {32588829}, issn = {2310-6972}, mesh = {Fecal Microbiota Transplantation ; *Feces/chemistry ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/metabolism/therapy ; Quality of Life ; }, abstract = {Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal inflammatory disorders with an unknown etiology. They are characterized by chronic recurrent inflammation of the intestinal mucosa and lead to a significant decrease in the quality of life and death of patients. IBD are associated with suppression of normal intestinal microflora, including a decrease in bacteria, producers of short chain fatty acids (SCFAs), exhibiting anti-inflammatory and protective properties. Among the various methods of intestinal microflora correction, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, is of a particular interest. As a result, a positive therapeutic effect is observed, accompanied by the restoration of the normal intestinal microflora of the patient. A significant drawback of the method is the lack of standardization. Metabolites produced by intestinal microflora, namely SCFAs, allow objective assessment of the functional state of the intestinal microbiota and, consequently, the success of the FMT procedure. Using gas chromatography and nuclear magnetic resonance spectroscopy techniques, we have analyzed concentrations and molar ratios of SCFAs in fecal samples of 60 healthy donors. Results were in good accord when comparing two methods as well as with published data. Analysis of SCFAs in feces of patients with UC (19 patients) and CD (17 patients) revealed a general decrease in the concentration of fatty acids in the experimental groups with significant fluctuations in the values in experimental groups compared to control group of healthy donors. On the limited group of IBD patients (6 patients with UC and 5 patients with CD) concentration of SCFAs before and within 30 days of observation after FMT was determined. It was shown that FMT had a significant impact on the SCFAs levels within 1 month term; tendency to reach characteristics of healthy donors is unambiguously traced for both diseases.}, }
@article {pmid32587239, year = {2020}, author = {Li, H and Xu, H and Li, Y and Jiang, Y and Hu, Y and Liu, T and Tian, X and Zhao, X and Zhu, Y and Wang, S and Zhang, C and Ge, J and Wang, X and Wen, H and Bai, C and Sun, Y and Song, L and Zhang, Y and Hui, R and Cai, J and Chen, J}, title = {Alterations of gut microbiota contribute to the progression of unruptured intracranial aneurysms.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {3218}, pmid = {32587239}, issn = {2041-1723}, mesh = {Animals ; Case-Control Studies ; Clostridiaceae/*metabolism ; Cohort Studies ; Disease Progression ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; *Intracranial Aneurysm/microbiology/pathology ; Male ; Mice ; Prognosis ; Risk Factors ; Taurine/*metabolism ; }, abstract = {Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.}, }
@article {pmid32585997, year = {2020}, author = {Horvath, A and Durdevic, M and Leber, B and di Vora, K and Rainer, F and Krones, E and Douschan, P and Spindelboeck, W and Durchschein, F and Zollner, G and Stauber, RE and Fickert, P and Stiegler, P and Stadlbauer, V}, title = {Changes in the Intestinal Microbiome during a Multispecies Probiotic Intervention in Compensated Cirrhosis.}, journal = {Nutrients}, volume = {12}, number = {6}, pages = {}, pmid = {32585997}, issn = {2072-6643}, support = {P24362//Austrian Science Fund/ ; }, mesh = {Aged ; Bacteria/classification/genetics ; Cohort Studies ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Liver Cirrhosis/*drug therapy ; Male ; Middle Aged ; *Probiotics/administration &amp; dosage/pharmacology/therapeutic use ; RNA, Ribosomal, 16S/genetics ; Randomized Controlled Trials as Topic ; }, abstract = {Probiotics have been used in trials to therapeutically modulate the gut microbiome and have shown beneficial effects in cirrhosis. However, their effect on the microbiome of cirrhosis patients is not fully understood yet. Here, we tested the effects of a multispecies probiotic on microbiome composition in compensated cirrhosis. The gut microbiome composition of 58 patients with compensated cirrhosis from a randomized controlled trial who received a daily dose of multispecies probiotics or placebo for six months was analysed by 16S rRNA gene sequencing. Microbiome composition of patients who received probiotics was enriched with probiotic strains and the abundance of Faecalibacterium prausnitzii, Syntrophococcus sucromutans, Bacteroides vulgatus, Alistipes shahii and a Prevotella species was increased in the probiotic group compared to the placebo group. Patients who had microbiome changes in response to probiotic treatment also showed a significant increase in neopterin and a significant decrease in faecal zonulin levels after intervention, which was not observed in placebo-treated patients or patients with unchanged microbiome compositions. In conclusion, multispecies probiotics may enrich the microbiome of compensated cirrhotic patients with probiotic bacteria during a six-month intervention and beneficially change the residential microbiome and gut barrier function.}, }
@article {pmid32585945, year = {2020}, author = {Leo, S and Lazarevic, V and Girard, M and Gaïa, N and Schrenzel, J and de Lastours, V and Fantin, B and Bonten, M and Carmeli, Y and Rondinaud, E and Harbarth, S and Huttner, BD}, title = {Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial.}, journal = {Microorganisms}, volume = {8}, number = {6}, pages = {}, pmid = {32585945}, issn = {2076-2607}, support = {282512//European Commission under the Seventh Framework Programme (FP7/2007) for Research and technology/ ; }, abstract = {Background: The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics of fecal microbiota changes in a sub-cohort of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. Methods: We sequenced fecal DNA obtained from 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding seven donors. Ten treatment-naïve controls from the same trial were included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (V3, V4 and V5). Results: Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). Bifidobacterium species, together with butyrate- and propionate-producing species from Lachnospiraceae and Ruminococcaceae families were significantly enriched in post-FMT microbiota of treated carriers. After FMT, the proportion of Enterobacteriaceae was lower compared to baseline but without statistical significance. Conclusions: Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE.}, }
@article {pmid32585148, year = {2020}, author = {Basson, AR and Zhou, Y and Seo, B and Rodriguez-Palacios, A and Cominelli, F}, title = {Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {226}, number = {}, pages = {1-11}, pmid = {32585148}, issn = {1878-1810}, support = {R01 DK055812/DK/NIDDK NIH HHS/United States ; }, mesh = {Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*therapy ; Transplantation, Autologous ; Treatment Outcome ; }, abstract = {The term autologous fecal microbiota transplantation (a-FMT) refers herein to the use of one's feces during a healthy state for later use to restore gut microbial communities after perturbations. Generally, heterologous fecal microbiota transplantation (h-FMT), where feces from a ``healthy" donor is transplanted into a person with illness, has been used to treat infectious diseases such as recurrent Clostridioides difficile infection (CDI), with cure rates of up to 90%. In humans, due to limited response to medicines, h-FMT has become a hallmark intervention to treat CDI. Extrapolating the benefits from CDI, h-FMT has been attempted in various diseases, including inflammatory bowel disease (IBD), but clinical response has been variable and less effective (ranging between 24% and 50%). Differences in h-FMT clinical response could be because CDI is caused by a Clostridial infection, whereas IBD is a complex, microbiome-driven immunological inflammatory disorder that presents predominantly within the gut wall of genetically-susceptible hosts. FMT response variability could also be due to differences in microbiome composition between donors, recipients, and within individuals, which vary with diet, and environments, across regions. While donor selection has emerged as a key factor in FMT success, the use of heterologous donor stool still places the recipient at risk of exposure to infectious/pathogenic microorganisms. As an implementable solution, herein we review the available literature on a-FMT, and list some considerations on the benefits of a-FMT for IBD.}, }
@article {pmid32584703, year = {2020}, author = {Gong, Z and Wang, Y}, title = {Immune Checkpoint Inhibitor-Mediated Diarrhea and Colitis: A Clinical Review.}, journal = {JCO oncology practice}, volume = {16}, number = {8}, pages = {453-461}, doi = {10.1200/OP.20.00002}, pmid = {32584703}, issn = {2688-1535}, mesh = {*Colitis/chemically induced/diagnosis/drug therapy ; Diarrhea/chemically induced/drug therapy ; Humans ; Immune Checkpoint Inhibitors ; Infliximab/adverse effects ; *Neoplasms ; }, abstract = {Immune-mediated diarrhea and colitis (IMDC) is among the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors (ICIs). Many factors will affect the risk of IMDC, including the type of ICI used, the type of underlying cancer, and patient characteristics. A recent study showed that preexisting inflammatory bowel disease significantly increases the risk of diarrhea and colitis with ICI treatment. In terms of management, early endoscopic evaluation improves clinical outcome by identifying high-risk patients who will benefit from early add-on immunosuppressants. Inflammatory markers, including fecal lactoferrin and calprotectin, are good screening tools to predict which patients are at risk for colitis. Calprotectin especially is associated with colitis outcome and can be used as a surrogate marker to follow treatment response. Corticosteroids remain the first-line medical treatment of IMDC management, and add-on therapy with vedolizumab or infliximab should be considered in selected patients. Fecal microbiota transplantation may be considered in refractory cases. The decision to resume ICI should be decided by balancing the risk of recurrent IMDC and the likelihood of benefiting from further ICI treatment. There is no clear evidence about whether the use of immunosuppressants will result in a worse cancer outcome. With emerging evidence, our understanding and management strategies are likely to evolve in the future.}, }
@article {pmid32583041, year = {2020}, author = {Kousgaard, SJ and Nielsen, HL and Kirk, KF and Thorlacius-Ussing, O}, title = {Faecal microbiota transplantation to chronic pouchitis improves quality of life: a pilot study.}, journal = {International journal of colorectal disease}, volume = {35}, number = {11}, pages = {2135-2136}, doi = {10.1007/s00384-020-03677-w}, pmid = {32583041}, issn = {1432-1262}, mesh = {Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Humans ; Pilot Projects ; Pouchitis/microbiology/*psychology/*therapy ; *Quality of Life ; Treatment Outcome ; }, }
@article {pmid32582330, year = {2020}, author = {Kamani, L}, title = {What gastroenterologists should know during COVID-19 Pandemic!.}, journal = {Pakistan journal of medical sciences}, volume = {36}, number = {COVID19-S4}, pages = {S124-S125}, pmid = {32582330}, issn = {1682-024X}, abstract = {The WHO has declared a Pandemic due to Novel Corona virus-19 (COVID-19). Patients usually have respiratory symptoms but gastrointestinal and hepatic dysfunction are not uncommon presentations and can lead to a delay in diagnosis and management. Virus shedding can continue even after the nasopharyngeal swab gets negative and could lead to faecal-oral transmission. The effects of COVID-19 on patients with decompensated liver disease is still not clear. Managing immunosuppressive drugs in liver transplant and inflammatory bowel disease is a major challenge without clear guidelines. Only emergency endoscopy is to be done with personal protection equipment. Chloroquine and Hydroxychloroquine has shown some beneficial effects and is being used off-label. Without effective treatment, it is imperative to take precautionary measures.}, }
@article {pmid32582202, year = {2020}, author = {Yan, Y and Zhou, X and Guo, K and Zhou, F and Yang, H}, title = {Chlorogenic Acid Protects Against Indomethacin-Induced Inflammation and Mucosa Damage by Decreasing Bacteroides-Derived LPS.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1125}, pmid = {32582202}, issn = {1664-3224}, mesh = {Animals ; Bacteroides/*drug effects/immunology/metabolism ; Bacteroides Infections/*immunology ; Chlorogenic Acid/*pharmacology ; Colitis/chemically induced/immunology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Indomethacin/toxicity ; Inflammation/chemically induced ; Intestinal Mucosa/*drug effects/immunology ; Lipopolysaccharides/metabolism ; Mice ; }, abstract = {Background: Chlorogenic acid (CGA), a natural bioactive polyphenol, exerts anti-inflammatory, antioxidant, and antibacterial effects that support the maintenance of intestinal health. However, the influence of CGA on gut microbiota and their metabolites, as well as its potential effects and mechanism of action in inflammatory bowel disease, remain to be elucidated. Methods: First, an oral gavage was used to administer CGA to indomethacin-treated mice. Then, fecal microbiota transplantation was performed to explore the role of intestinal microbiota in indomethacin-induced inflammation. Results: CGA treatment protected against body weight loss, damage to intestinal morphology and integrity, inflammation, and alteration of microbiota composition in indomethacin-treated mice. Interestingly, CGA failed to inhibit inflammation or protect intestine integrity in mice treated with antibiotics. Notably, mice who had been colonized with intestinal microbiota from CGA-treated or CGA-and-indomethacin-treated mice, through the fecal microbiota transplantation program, were protected from indomethacin-induced inflammation, growth of Bacteroides, and the accumulation of Bacteroides-derived LPS, in congruence with those who had been treated with CGA. Conclusion: The results suggest that CGA may protect intestine integrity and alleviate inflammatory responses, primarily by inhibiting the growth of Bacteroides and the accumulation of Bacteroides-derived LPS, in indomethacin-induced colitis. This newly identified mechanism broadens our knowledge of how CGA exerts protective effects on intestinal inflammation and provides strategies for the prevention of gastrointestinal mucosal damage in patients treated with indomethacin.}, }
@article {pmid32582121, year = {2020}, author = {Liang, W and Zhao, L and Zhang, J and Fang, X and Zhong, Q and Liao, Z and Wang, J and Guo, Y and Liang, H and Wang, L}, title = {Colonization Potential to Reconstitute a Microbe Community in Pseudo Germ-Free Mice After Fecal Microbe Transplant From Equol Producer.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1221}, pmid = {32582121}, issn = {1664-302X}, abstract = {Human intestinal microbiota plays a crucial role in the conversion of isoflavones into equol. Usually, human microbiota-associated (HMA) animal models are used, since it is difficult to establish the mechanism and causal relationship between equol and microbiota in human studies. Currently, several groups have successfully established HMA animal models that produce equol through germ-free mice or rats; however, the HMA model of producing equol through pseudo germ-free mice has not been established. The objective of this study is to establish an HMA mice model for equol production through pseudo germ-free mice, mimicking the gut microbiota of an adult human equol producer. First, a higher female equol producer was screened as a donor from 15 volunteers. Then, mice were exposed to vancomycin, neomycin sulfate, metronidazole, and ampicillin for 3 weeks to obtain pseudo germ-free mice. Finally, pseudo germ-free mice were inoculated with fecal microbiota of the equol producer for 3 weeks to establish HMA mice of producing equol. The results showed that (i) the ability to produce equol was partially transferred from the donor to the HMA mice. (ii) Most of the original intestinal microbiota of mice were eliminated after broad-spectrum antibiotic administration. (iii) The taxonomy data from HMA mice revealed similar taxa to the donor sample, and the species richness returned to the level close to the donor. (iv) The family Coriobacteriaceae and genera Collinsella were successfully transferred from the donor to HMA mice. In conclusion, the HMA mice model for equol production, based on pseudo germ-free mice, can replace the model established by germ-free mice. The model also provides a basis for studying microbiota during the conversion from isoflavones into equol.}, }
@article {pmid32580023, year = {2021}, author = {Inamura, K}, title = {Gut microbiota contributes towards immunomodulation against cancer: New frontiers in precision cancer therapeutics.}, journal = {Seminars in cancer biology}, volume = {70}, number = {}, pages = {11-23}, doi = {10.1016/j.semcancer.2020.06.006}, pmid = {32580023}, issn = {1096-3650}, mesh = {Animals ; Antineoplastic Agents/*administration &amp; dosage ; *Gastrointestinal Microbiome ; Host Microbial Interactions ; Humans ; *Immunomodulation ; Immunotherapy/*methods ; Neoplasms/*drug therapy/*immunology/microbiology ; Prebiotics/*administration &amp; dosage ; Precision Medicine ; }, abstract = {The microbiota influences human health and the development of diverse diseases, including cancer. Microbes can influence tumor initiation and development in either a positive or negative manner. In addition, the composition of the gut microbiota affects the efficacy and toxicity of cancer therapeutics as well as therapeutic resistance. The striking impact of microbiota on oncogenesis and cancer therapy provides compelling evidence to support the notion that manipulating microbial networks represents a promising strategy for treating and preventing cancer. Specific microbes or the microbial ecosystem can be modified via a multiplicity of processes, and therapeutic methods and approaches have been evolving. Microbial manipulation can be applied as an adjunct to traditional cancer therapies such as chemotherapy and immunotherapy. Furthermore, this approach displays great promise as a stand-alone therapy following the failure of standard therapy. Moreover, such strategies may also benefit patients by avoiding the emergence of toxic side effects that result in treatment discontinuation. A better understanding of the host-microbial ecosystem in patients with cancer, together with the development of methodologies for manipulating the microbiome, will help expand the frontiers of precision cancer therapeutics, thereby improving patient care. This review discusses the roles of the microbiota in oncogenesis and cancer therapy, with a focus on efforts to harness the microbiota to fight cancer.}, }
@article {pmid32579743, year = {2020}, author = {Busnelli, M and Manzini, S and Jablaoui, A and Bruneau, A and Kriaa, A and Philippe, C and Arnaboldi, F and Colombo, A and Ferrari, B and Ambrogi, F and Maguin, E and Rhimi, M and Chiesa, G and Gérard, P}, title = {Fat-Shaped Microbiota Affects Lipid Metabolism, Liver Steatosis, and Intestinal Homeostasis in Mice Fed a Low-Protein Diet.}, journal = {Molecular nutrition &amp; food research}, volume = {64}, number = {15}, pages = {e1900835}, doi = {10.1002/mnfr.201900835}, pmid = {32579743}, issn = {1613-4133}, mesh = {Animals ; Cecum/microbiology ; Cholesterol/blood ; *Diet, High-Fat ; Diet, Protein-Restricted/*adverse effects ; Dysbiosis/genetics/microbiology ; Eating ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Gene Expression ; Male ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/*microbiology/pathology ; Organ Size ; Triglycerides/blood ; Weight Gain ; }, abstract = {SCOPE: Protein malnutrition is characterized by stunted growth, hepatic steatosis and a damaged gut mucosal architecture. Since high-fat shaped gut microbiota (HFM) has an increased ability in providing nutrients and energy from food to the host, the aim of this study is to determine whether such a microbiota could beneficially impact on the consequences of malnutrition.<br><br>METHODS AND RESULTS: The cecal content of specific pathogen free C57Bl/6J mice fed a high-fat diet or a low-protein diet is transplanted in two groups of germ-free C57Bl/6J recipient mice, which are subsequently fed a low-protein diet for 8 weeks. Body weight gain is comparable between the two groups of microbiota-recipient mice. The HFM led to a worsening of microvesicular steatosis and a decrease of plasma lipids compared to the low-protein shaped microbiota. In the small intestine of mice receiving the HFM, although significant histological differences are not observed, the expression of antimicrobial genes promoting oxidative stress and immune response at the ileal epithelium (Duox2, Duoxa2, Saa1, Ang4, Defa5) is increased.<br><br>CONCLUSION: The transplant of HFM in mice fed a low-protein diet represents a noxious stimulus for the ileal mucosa and impairs hepatic lipoprotein secretion, favoring the occurrence of hepatic microvesicular steatosis.}, }
@article {pmid32577835, year = {2020}, author = {McQuade, JL and Ologun, GO and Arora, R and Wargo, JA}, title = {Gut Microbiome Modulation Via Fecal Microbiota Transplant to Augment Immunotherapy in Patients with Melanoma or Other Cancers.}, journal = {Current oncology reports}, volume = {22}, number = {7}, pages = {74}, pmid = {32577835}, issn = {1534-6269}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; }, mesh = {Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Melanoma/microbiology/*therapy ; Neoplasms/*therapy ; }, abstract = {PURPOSE OF REVIEW: We review emerging evidence regarding the impact of gut microbes on antitumor immunity, and ongoing efforts to translate this in clinical trials.<br><br>RECENT FINDINGS: Pre-clinical models and human cohort studies support a role for gut microbes in modulating overall immunity and immunotherapy response, and numerous trials are now underway exploring strategies to modulate gut microbes to enhance responses to cancer therapy. This includes the use of fecal microbiota transplant (FMT), which is being used to treat patients with Clostridium difficile infection among other non-cancer indications. The use of FMT is now being extended to modulate gut microbes in patients being treated with cancer immunotherapy, with the goal of enhancing responses and/or to ameliorate toxicity. However, significant complexities exist with such an approach and will be discussed herein. Data from ongoing studies of FMT in cancer will provide critical insights for optimization of this approach.}, }
@article {pmid32575899, year = {2020}, author = {Giannone, G and Ghisoni, E and Genta, S and Scotto, G and Tuninetti, V and Turinetto, M and Valabrega, G}, title = {Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy.}, journal = {International journal of molecular sciences}, volume = {21}, number = {12}, pages = {}, pmid = {32575899}, issn = {1422-0067}, mesh = {Animals ; Humans ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Immunotherapy/*methods ; Neoplasms/immunology/metabolism/*therapy ; Signal Transduction/drug effects ; Tumor Microenvironment/drug effects ; Tumor-Associated Macrophages/drug effects/immunology/metabolism ; }, abstract = {Immune checkpoint inhibitors (ICIs) have changed therapeutic algorithms in several malignancies, although intrinsic and secondary resistance is still an issue. In this context, the dysregulation of immuno-metabolism plays a leading role both in the tumor microenvironment (TME) and at the host level. In this review, we summarize the most important immune-metabolic factors and how they could be exploited therapeutically. At the cellular level, an increased concentration of extracellular adenosine as well as the depletion of tryptophan and uncontrolled activation of the PI3K/AKT pathway induces an immune-tolerant TME, reducing the response to ICIs. Moreover, aberrant angiogenesis induces a hypoxic environment by recruiting VEGF, Treg cells and immune-suppressive tumor associated macrophages (TAMs). On the other hand, factors such as gender and body mass index seem to affect the response to ICIs, while the microbiome composition (and its alterations) modulates both the response and the development of immune-related adverse events. Exploiting these complex mechanisms is the next goal in immunotherapy. The most successful strategy to date has been the combination of antiangiogenic drugs and ICIs, which prolonged the survival of patients with non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC), while results from tryptophan pathway inhibition studies are inconclusive. New exciting strategies include targeting the adenosine pathway, TAMs and the microbiota with fecal microbiome transplantation.}, }
@article {pmid32574836, year = {2020}, author = {Zhang, F and Chen, H and Zhang, R and Liu, Y and Kong, N and Guo, Y and Xu, M}, title = {5-Fluorouracil induced dysregulation of the microbiome-gut-brain axis manifesting as depressive like behaviors in rats.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1866}, number = {10}, pages = {165884}, doi = {10.1016/j.bbadis.2020.165884}, pmid = {32574836}, issn = {1879-260X}, mesh = {Animals ; Antimetabolites, Antineoplastic/*adverse effects ; Behavior, Animal/drug effects ; Colorectal Neoplasms/drug therapy ; Depression/*chemically induced/diagnosis/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Fluorouracil/*adverse effects ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Intestinal Mucosa/metabolism/microbiology ; Male ; Prefrontal Cortex/*metabolism ; Rats ; }, abstract = {Disturbances of the gut microbiome have been widely suggested to be associated with 5-fluorouracil (5-Fu) induced digestive pathologies. Furthermore, it has been elucidated that the gut microbiome may play a key role in the pathogenesis of depressive disorders via the microbiota-gut-brain axis. Despite the speculation, there exists no direct evidence proving the causality between disturbances in the gut microbiome induced by 5-Fu and depressive mood dysregulation. Herein, behavioral testing was used to evaluate depressive-like behaviors in 5-Fu treated rats. Subsequently, the gut microbiota and prefrontal cortex (PFC) metabolic were analyzed by 16S rRNA sequencing and [1]H nuclear magnetic resonance ([1]H NMR). To clarify the association between the gut microbiota and their role on depressive-like behaviors caused by 5-Fu, a fecal microbiota transplantation (FMT) experiment was carried out. The results suggested that 5-Fu could significantly alter the diversity and abundance of the gut microbiome, and induce PFC metabolic disorders, as well as depressive behaviors in rats. Transplantation of fecal microbiota from healthy control into 5-Fu treated rats significantly alleviated the PFC metabolic disorder and depressive-like behaviors. In conclusion, this study demonstrated that the gut microbiome was actively involved in the occurrence of 5-Fu induced depressive-like behaviors, and manipulation of specific gut microbiome parameters may serve as a promising novel target for side effects of 5-Fu treatment.}, }
@article {pmid32574415, year = {2021}, author = {Bilinski, J and Lis, K and Tomaszewska, A and Pechcinska, A and Grzesiowski, P and Dzieciatkowski, T and Walesiak, A and Gierej, B and Ziarkiewicz-Wróblewska, B and Tyszka, M and Kacprzyk, P and Chmielewska, L and Waszczuk-Gajda, A and Wiktor-Jedrzejczak, W and Basak, GW}, title = {Eosinophilic gastroenteritis and graft-versus-host disease induced by transmission of Norovirus with fecal microbiota transplant.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {23}, number = {1}, pages = {e13386}, doi = {10.1111/tid.13386}, pmid = {32574415}, issn = {1399-3062}, mesh = {*Enteritis ; *Eosinophilia ; *Fecal Microbiota Transplantation ; *Gastritis ; *Graft vs Host Disease ; Humans ; Norovirus ; }, abstract = {Fecal microbiota transplantation (FMT) was performed to decolonize gastrointestinal tract from antibiotic-resistant bacteria before allogeneic hematopoietic cells transplantation (alloHCT). AlloHCT was complicated by norovirus gastroenteritis, acute graft-versus-host disease, and eosinophilic pancolitis. Norovirus was identified in samples from FMT material. Symptoms resolved after steroids course and second norovirus-free FMT from another donor.}, }
@article {pmid32572461, year = {2021}, author = {Mangioni, D and Alagna, L and Gori, A and Bandera, A}, title = {Fecal Microbiota Transplant: Keep Calm and Carry On, Learning From Experience.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {72}, number = {7}, pages = {1296-1297}, doi = {10.1093/cid/ciaa846}, pmid = {32572461}, issn = {1537-6591}, mesh = {*Bacteremia ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gram-Negative Bacteria ; Humans ; *Microbiota ; }, }
@article {pmid32572223, year = {2020}, author = {Hughes, DA and Bacigalupe, R and Wang, J and Rühlemann, MC and Tito, RY and Falony, G and Joossens, M and Vieira-Silva, S and Henckaerts, L and Rymenans, L and Verspecht, C and Ring, S and Franke, A and Wade, KH and Timpson, NJ and Raes, J}, title = {Genome-wide associations of human gut microbiome variation and implications for causal inference analyses.}, journal = {Nature microbiology}, volume = {5}, number = {9}, pages = {1079-1087}, pmid = {32572223}, issn = {2058-5276}, support = {MC_UU_00011/6/MRC_/Medical Research Council/United Kingdom ; MC_UU_12013/3/MRC_/Medical Research Council/United Kingdom ; 202802/WT_/Wellcome Trust/United Kingdom ; 202802/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; C18281/A19169/CRUK_/Cancer Research UK/United Kingdom ; BRC-1215-20011/DH_/Department of Health/United Kingdom ; 19169/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 204813/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Bifidobacterium/genetics ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; *Genome-Wide Association Study ; Genotype ; Humans ; Mice ; Microbiota/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Recent population-based[1-4] and clinical studies[5] have identified a range of factors associated with human gut microbiome variation. Murine quantitative trait loci[6], human twin studies[7] and microbiome genome-wide association studies[1,3,8-12] have provided evidence for genetic contributions to microbiome composition. Despite this, there is still poor overlap in genetic association across human studies. Using appropriate taxon-specific models, along with support from independent cohorts, we show an association between human host genotype and gut microbiome variation. We also suggest that interpretation of applied analyses using genetic associations is complicated by the probable overlap between genetic contributions and heritable components of host environment. Using faecal 16S ribosomal RNA gene sequences and host genotype data from the Flemish Gut Flora Project (n = 2,223) and two German cohorts (FoCus, n = 950; PopGen, n = 717), we identify genetic associations involving multiple microbial traits. Two of these associations achieved a study-level threshold of P = 1.57 × 10[-10]; an association between Ruminococcus and rs150018970 near RAPGEF1 on chromosome 9, and between Coprococcus and rs561177583 within LINC01787 on chromosome 1. Exploratory analyses were undertaken using 11 other genome-wide associations with strong evidence for association (P < 2.5 × 10[-8]) and a previously reported signal of association between rs4988235 (MCM6/LCT) and Bifidobacterium. Across these 14 single-nucleotide polymorphisms there was evidence of signal overlap with other genome-wide association studies, including those for age at menarche and cardiometabolic traits. Mendelian randomization analysis was able to estimate associations between microbial traits and disease (including Bifidobacterium and body composition); however, in the absence of clear microbiome-driven effects, caution is needed in interpretation. Overall, this work marks a growing catalogue of genetic associations that will provide insight into the contribution of host genotype to gut microbiome. Despite this, the uncertain origin of association signals will likely complicate future work looking to dissect function or use associations for causal inference analysis.}, }
@article {pmid32570299, year = {2020}, author = {Shasthry, SM}, title = {Fecal microbiota transplantation in alcohol related liver diseases.}, journal = {Clinical and molecular hepatology}, volume = {26}, number = {3}, pages = {294-301}, pmid = {32570299}, issn = {2287-285X}, mesh = {*Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Liver Diseases, Alcoholic/pathology/*therapy ; Severity of Illness Index ; }, abstract = {The current standard of care for severe alcoholic hepatitis (SAH) has several limitations in that only up to one-third of patients are eligible for steroid therapy. Additionally, steroids have their own issues: a portion of patients do not respond, while there is doubtful long-term benefit in those who do and a large proportion are ineligible to receive steroids entirely and hence have no definitive options for treatment. As such, there is a large gap between the problem and the available solutions. Alcohol causes dysbiosis and also disrupts gut barrier function, consequently promoting the translocation of microbial lipopolysaccharide into the portal circulation and liver. Therefore, probiotics, prebiotics, antibiotics, or transplantation of gut microbiota are likely to attenuate the dysbiosis-related liver insult. Fecal microbiota transplantation (FMT) is expected to have a role in managing alcoholic liver disease in general and SAH in particular by correcting dysbiosis, the primary insult. Results from mouse studies have suggested beyond doubt that alcohol-related liver injury is transferrable and also treatable by adopting FMT from suitable donors. Initial human trials from our center have affirmed benefits in human subjects with SAH as well, with both improvements in disease severity and as well as the rate of survival. Further studies addressing the head-to-head comparison of steroids and FMT are ongoing. Available preliminary data are promising and FMT and/or gut microbial modulation might become the standard of care in the near future for managing alcohol-related liver diseases, especially alcoholic hepatitis, with greater applicability, improved acceptability, and minimal side effects.}, }
@article {pmid32564632, year = {2020}, author = {Suraya, R and Nagano, T and Kobayashi, K and Nishimura, Y}, title = {Microbiome as a Target for Cancer Therapy.}, journal = {Integrative cancer therapies}, volume = {19}, number = {}, pages = {1534735420920721}, pmid = {32564632}, issn = {1552-695X}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Neoplasms/therapy ; *Probiotics ; }, abstract = {Recently, the microbiome has been gaining traction as a major player regulating various functions that correlate with many pathological conditions, including cancer. The central gut microbiota population has the capability to regulate normal inflammatory, immune, and metabolic functions, and disturbance in the balance of the normal microbiota population can subsequently induce pathological responses that closely relate with the mechanistic development and progression of cancer in various forms and sites. As a disease with major socioeconomic burden partly due to its current therapeutic options, modulating the imbalanced gut microbiota represents a novel option not only as an adjuvant therapy to relieve cancer treatment-related symptoms but also to influence cancer progression itself. In this review, we will discuss how the microbiome, specifically the gut microbiota, could affect cancer pathogenesis and what the effect of gut microbiota-targeting treatment options have on the many aspects of cancer pathologies based on the knowledge of recent years.}, }
@article {pmid32563025, year = {2020}, author = {Wang, Y and Ren, R and Sun, G and Peng, L and Tian, Y and Yang, Y}, title = {Pilot study of cytokine changes evaluation after fecal microbiota transplantation in patients with ulcerative colitis.}, journal = {International immunopharmacology}, volume = {85}, number = {}, pages = {106661}, doi = {10.1016/j.intimp.2020.106661}, pmid = {32563025}, issn = {1878-1705}, mesh = {Adolescent ; Adult ; Aged ; Blood Sedimentation ; C-Reactive Protein/analysis ; Colitis, Ulcerative/blood/immunology/pathology/*therapy ; Cytokines/*blood ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Pilot Projects ; Vascular Cell Adhesion Molecule-1/blood ; Young Adult ; }, abstract = {AIMS: To evaluate the changes of serum cytokines levels after fecal microbiota transplantation (FMT) in patients with active ulcerative colitis (UC) and the correlation with UC disease activity.<br><br>METHODS: Patients with active UC who meet the inclusion and exclusion criteria were recruited, and received FMT from a single donor for three times with an interval of 2-3 months. Serum samples were collected before every FMT. Clinical responses to FMT were assessed according to the criteria of Mayo score. 41 serum cytokines, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were quantitatively detected. Changes in serum cytokines levels after FMT and their correlation with CRP, ESR and Mayo scores were investigated.<br><br>RESULTS: 16 active UC patients were enrolled, and 14(87.5%) patients achieved clinical response to FMT. Compared with those before FMT, serum concentrations of IL-1Ra, IL-6, IP-10 and ENA-78 decreased significantly after the second FMT (P&#xa0;<&#xa0;0.05), and serum concentrations of MEC, VCAM-1 and G-CSF decreased significantly after both the first and second FMT (P&#xa0;<&#xa0;0.05). Serum levels of IL-6, IL-1Ra and VCAM-1 were all significantly positively correlated with CRP and ESR. Serum level of IP-10 was significantly positively correlated with CRP, ESR and Mayo score. Serum level of G-CSF was significantly positively correlated with Mayo score.<br><br>CONCLUSIONS: FMT may play a therapeutic role partly through modulating the host immune response. IL-6, IL-1Ra, IP-10, VCAM-1 and G-CSF may be biomarkers to evaluate the effect of FMT on UC.}, }
@article {pmid32560820, year = {2020}, author = {Udomsopagit, T and Miwa, A and Seki, M and Shimbori, E and Kadota, Y and Tochio, T and Sonoyama, K}, title = {Intestinal microbiota transplantation reveals the role of microbiota in dietary regulation of RegIIIβ and RegIIIγ expression in mouse intestine.}, journal = {Biochemical and biophysical research communications}, volume = {529}, number = {1}, pages = {64-69}, doi = {10.1016/j.bbrc.2020.05.150}, pmid = {32560820}, issn = {1090-2104}, mesh = {Animals ; Diet ; Diet, High-Fat ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Ileum/metabolism ; Interleukins/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pancreatitis-Associated Proteins/*blood/*genetics ; RNA, Messenger/genetics/metabolism ; Trisaccharides/administration &amp; dosage ; Interleukin-22 ; }, abstract = {RegIIIβ and RegIIIγ are antimicrobial peptides expressed in intestinal epithelial cells. Expression of these peptides is reportedly decreased by high-fat diet (HFD) and increased by indigestible oligosaccharides in mice. Clearly, these dietary regimens change the structure of intestinal microbiota. We employed an intestinal microbiota transplantation (IMT) to test whether diet-induced changes in the expression of these peptides are mediated by gut microbiota. C57BL/6J mice were fed either a normal-fat diet (NFD), a HFD, or a NFD supplemented with or without 1-kestose (KES), an indigestible oligosaccharide. Ileal RegIIIβ and RegIIIγ mRNA levels were lower in mice receiving IMT from HFD-fed mice than in those receiving NFD-fed mice and higher in mice receiving IMT from KES-supplemented mice than in those receiving the mice without KES supplementation. Western blot analysis showed that serum RegIIIβ levels changed in parallel with the ileal mRNA levels. We propose that HFD- and KES-induced changes in the ileal RegIIIβ and RegIIIγ expression and in the circulating RegIIIβ levels are mediated, at least in part, by intestinal microbiota.}, }
@article {pmid32553109, year = {2020}, author = {Watterson, WJ and Tanyeri, M and Watson, AR and Cham, CM and Shan, Y and Chang, EB and Eren, AM and Tay, S}, title = {Droplet-based high-throughput cultivation for accurate screening of antibiotic resistant gut microbes.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32553109}, issn = {2050-084X}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; RC2 DK122394/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; 2018-2019//Samuel and Emma Winters Foundation/International ; }, mesh = {Bacteria/*drug effects ; Bacteriological Techniques/instrumentation/*methods ; *Drug Resistance, Bacterial ; *Gastrointestinal Microbiome ; High-Throughput Screening Assays/instrumentation/*methods ; }, abstract = {Traditional cultivation approaches in microbiology are labor-intensive, low-throughput, and yield biased sampling of environmental microbes due to ecological and evolutionary factors. New strategies are needed for ample representation of rare taxa and slow-growers that are often outcompeted by fast-growers in cultivation experiments. Here we describe a microfluidic platform that anaerobically isolates and cultivates microbial cells in millions of picoliter droplets and automatically sorts them based on colony density to enhance slow-growing organisms. We applied our strategy to a fecal microbiota transplant (FMT) donor stool using multiple growth media, and found significant increase in taxonomic richness and larger representation of rare and clinically relevant taxa among droplet-grown cells compared to conventional plates. Furthermore, screening the FMT donor stool for antibiotic resistance revealed 21 populations that evaded detection in plate-based assessment of antibiotic resistance. Our method improves cultivation-based surveys of diverse microbiomes to gain deeper insights into microbial functioning and lifestyles.}, }
@article {pmid32552337, year = {2020}, author = {Allegretti, JR and Elliott, RJ and Ladha, A and Njenga, M and Warren, K and O'Brien, K and Budree, S and Osman, M and Fischer, M and Kelly, CR and Kassam, Z}, title = {Stool processing speed and storage duration do not impact the clinical effectiveness of fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1806-1808}, pmid = {32552337}, issn = {1949-0984}, mesh = {Bacteria/chemistry/classification/genetics/isolation &amp; purification ; Biological Specimen Banks ; Clostridioides difficile/physiology ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/*chemistry/microbiology ; Freezing ; Humans ; Preservation, Biological/instrumentation/*methods ; }, }
@article {pmid32552149, year = {2020}, author = {Magdziak, A and Szlak, J and Mróz, A and Wieszczy, P and Zagórowicz, E}, title = {A stool test in patients with active ulcerative colitis helps exclude cytomegalovirus disease.}, journal = {Scandinavian journal of gastroenterology}, volume = {55}, number = {6}, pages = {664-670}, doi = {10.1080/00365521.2020.1771760}, pmid = {32552149}, issn = {1502-7708}, mesh = {Adolescent ; Adult ; Aged ; Colitis, Ulcerative/*complications/pathology/surgery ; Colon/*pathology/virology ; Cytomegalovirus/genetics/isolation &amp; purification ; Cytomegalovirus Infections/*complications/diagnosis/pathology ; DNA, Viral/*analysis ; Feces/*virology ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Polymerase Chain Reaction ; Sensitivity and Specificity ; Young Adult ; }, abstract = {Objectives: In severe ulcerative colitis (UC) bowel biopsy is recommended to detect the cytomegalovirus (CMV) infection capable of complicating the course of the disease. Histopathology with immunohistochemistry (IHC) is time-consuming, and a blood polymerase chain reaction (PCR) for CMV DNA is used as an alternative, notwithstanding nothing more than a moderate correlation between the two. We aimed to detect CMV DNA in the stools of patients with active UC, and to compare the results with CMV IHC in bowel biopsies.Materials and methods: Measurement of CMV DNA in stools (copies/ml) entailed PCR, while biopsies assessed inflammation activity (Geboes scale), as well as counts of numbers of CMV IHC-positive cells/biopsy. The severity of UC was assessed using the Mayo score, stool calprotectin and concentrations of C-reactive protein in the blood.Results: 89 of the above pairs of tests for CMV were performed among 75 patients. CMV was detected in 36/89 stool specimens and 19/89 bowel biopsies. The sensitivity of the stool-CMV PCR was thus 84.7%, while specificity was of 71.4%. The negative predictive value was 94.3% and the positive predictive value 44.4%. No difference in the severity of UC was noted between the stool CMV DNA positive and negative groups. Similarly, there was no difference in the severity of UC between the CMV IHC positive and negative groups, except for the Geboes score, more often found to be higher in CMV IHC-positive patients (p = .002).Conclusions: CMV DNA was detected in the stools of 40.4% of patients with active UC. A negative test result may help to exclude bowel CMV disease.}, }
@article {pmid32550753, year = {2020}, author = {Little, R and Wine, E and Kamath, BM and Griffiths, AM and Ricciuto, A}, title = {Gut microbiome in primary sclerosing cholangitis: A review.}, journal = {World journal of gastroenterology}, volume = {26}, number = {21}, pages = {2768-2780}, pmid = {32550753}, issn = {2219-2840}, mesh = {Animals ; Anti-Bacterial Agents/*administration &amp; dosage/adverse effects ; Bile Acids and Salts/metabolism ; Biliary Tract/immunology/metabolism ; Cholangitis, Sclerosing/drug therapy/*immunology/microbiology ; Disease Models, Animal ; Dysbiosis/drug therapy/*immunology/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*immunology ; Humans ; Inflammatory Bowel Diseases/*complications/immunology/microbiology ; Intestinal Mucosa/immunology/metabolism/microbiology ; Mice ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by biliary inflammation and stricturing. Exploration of the pathogenesis of PSC in light of its association with inflammatory bowel disease (IBD) and the "gut-liver" axis is an emerging area of interest. A growing number of studies have begun to elucidate the role of the gut microbiota, its metabolites and its influence on host immune responses in the development of PSC and PSC-IBD. Studies of the fecal microbiota have highlighted enriched levels of certain species, including Veillonella, Streptococcus and Enterococcus, among others. A heightened immune response to enteric dysbiosis and bacterial translocation have also been implicated. For example, Klebsiella pneumoniae strains derived from gnotobiotic mice transplanted with PSC-IBD microbiota were found to induce pore formation in human intestinal epithelial cells and enhanced Th17 responses. Gut microbes have additionally been hypothesized to be implicated in PSC pathogenesis through their role in the synthesis of various metabolites, including bile acids (BAs), which function as signaling molecules with important gut and hepatic effects. An expanded knowledge of the gut microbiome as it relates to PSC offers critical insight into the development of microbe-altering therapeutic interventions, such as antibiotics, nutritional interventions and fecal microbial transplantation. Some of these have already shown some preliminary evidence of benefit. Despite exciting progress in the field, much work remains to be done; areas that are particularly lacking include functional characterization of the microbiome and examination of pediatric populations. In this review, we summarize studies that have investigated the microbiome in PSC and PSC-IBD as well as putative mechanisms, including the potential role of metabolites, such as BAs. We then briefly review the evidence for interventions with microbe-altering properties for treating PSC.}, }
@article {pmid32548192, year = {2020}, author = {Massaro, M and Vansia, J and McGill, S}, title = {Ulcerative Proctitis in a Patient With a History of Fecal Microbiota Transplant for Clostridioides difficile Infection.}, journal = {ACG case reports journal}, volume = {7}, number = {4}, pages = {e00364}, pmid = {32548192}, issn = {2326-3253}, abstract = {Fecal microbiota transplantation (FMT) effectively treats Clostridioides difficile infection and alters the gut microbiota in the long term, but potential adverse effects are poorly understood. We report a man with a family history of ulcerative colitis who developed ulcerative proctitis within a year of FMT.}, }
@article {pmid32548190, year = {2020}, author = {Fasanello, MK and Robillard, KT and Boland, PM and Bain, AJ and Kanehira, K}, title = {Use of Fecal Microbial Transplantation for Immune Checkpoint Inhibitor Colitis.}, journal = {ACG case reports journal}, volume = {7}, number = {4}, pages = {e00360}, pmid = {32548190}, issn = {2326-3253}, abstract = {Immune checkpoint inhibitors (ICIs) can result in immune-related adverse events which require rapid identification and treatment. Gastrointestinal immune-related adverse events are among the most frequent and severe of these events. ICI colitis can be refractory to current therapies such as corticosteroids and biologic therapy. Fecal microbiota transplantation (FMT) is currently used in cases of recurrent Clostridioides difficile colitis. Many investigations are underway to test the utility of FMT for additional indications, including inflammatory bowel disease (IBD). We present a 71-year-old man with ICI colitis that was nonresponsive to currently defined management options and treated with benefit from FMT.}, }
@article {pmid32547513, year = {2020}, author = {Chong, R and Cheng, Y and Hogg, CJ and Belov, K}, title = {Marsupial Gut Microbiome.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1058}, pmid = {32547513}, issn = {1664-302X}, abstract = {The study of the gut microbiome in threatened wildlife species has enormous potential to improve conservation efforts and gain insights into host-microbe coevolution. Threatened species are often housed in captivity, and during this process undergo considerable changes to their gut microbiome. Studying the gut microbiome of captive animals therefore allows identification of dysbiosis and opportunities for improving management practices in captivity and for subsequent translocations. Manipulation of the gut microbiome through methods such as fecal transplant may offer an innovative means of restoring dysbiotic microbiomes in threatened species to provide health benefits. Finally, characterization of the gut microbiome (including the viral components, or virome) provides important baseline health information and may lead to discovery of significant microbial pathogens. Here we summarize our current understanding of microbiomes in Australian marsupial species.}, }
@article {pmid32544438, year = {2020}, author = {Kaakoush, NO}, title = {Sutterella Species, IgA-degrading Bacteria in Ulcerative Colitis.}, journal = {Trends in microbiology}, volume = {28}, number = {7}, pages = {519-522}, doi = {10.1016/j.tim.2020.02.018}, pmid = {32544438}, issn = {1878-4380}, mesh = {Burkholderiales/*metabolism ; Colitis, Ulcerative/*microbiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Immunoglobulin A/*metabolism ; *Treatment Failure ; }, abstract = {Recent reports link Sutterella with gastrointestinal diseases, the most intriguing being therapeutic failure in ulcerative colitis (UC). Sutterella does not appear to induce substantial inflammation; rather, it has a capacity to degrade IgA. This activity, however, is not conserved, presenting a key target to deciphering the influence of Sutterella on the host.}, }
@article {pmid32543727, year = {2021}, author = {Polepole, P and Bartenslager, A and Liu, Y and Petro, TM and Fernando, S and Zhang, L}, title = {Epstein-Barr virus-immortalized B lymphocytes exacerbate experimental autoimmune encephalomyelitis in xenograft mice.}, journal = {Journal of medical virology}, volume = {93}, number = {6}, pages = {3813-3823}, pmid = {32543727}, issn = {1096-9071}, support = {D43 TW010354/TW/FIC NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; B-Lymphocytes/*immunology/physiology/*virology ; CD8-Positive T-Lymphocytes/immunology ; *Cell Proliferation ; Central Nervous System/pathology ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/*immunology/physiopathology ; Female ; Herpesvirus 4, Human/*immunology ; Heterografts ; Humans ; Lymphocyte Activation/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis/immunology ; }, abstract = {Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein-Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV-infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans and is a well-established rodent model for human MS. We have found that xenografts of EBV-immortalized B lymphocytes, which partially resemble the hyperproliferation of EBV-infected cells in IM, exacerbate autoimmune responses in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice. After remission, an additional challenge with EBV-immortalized cells induces a relapse in EAE. Moreover, xenografts with EBV-immortalized cells tighten the integrity of the blood-brain barrier (BBB) in the thalamus and hypothalamus areas of the mouse brains. Genomic sequences of prokaryotic 16S ribosomal RNA presented in the feces reveal that EBV-immortalized cells significantly change the diversities of microbial populations. Our data collectively suggest that EBV-mediated proliferation of B lymphocytes may be a risk factor for the exacerbation of MS, which are associated with gut microbiome changes and BBB modulations. Furthermore, multiple xenografts of EBV-immortalized cells into C57BL/6 mice could serve as a useful model for human relapsing-remitting MS with predictable severity and timing.}, }
@article {pmid32539741, year = {2020}, author = {Chinna Meyyappan, A and Forth, E and Wallace, CJK and Milev, R}, title = {Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review.}, journal = {BMC psychiatry}, volume = {20}, number = {1}, pages = {299}, pmid = {32539741}, issn = {1471-244X}, support = {//CIHR/Canada ; }, mesh = {Anxiety ; *Autism Spectrum Disorder ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {BACKGROUND: The Gut-Brain-Axis is a bidirectional signaling pathway between the gastrointestinal (GI) tract and the brain. The hundreds of trillions of microorganisms populating the gastrointestinal tract are thought to modulate this connection, and have far reaching effects on the immune system, central and autonomic nervous systems, and GI functioning. These interactions Diagnostic and statistical manual of mental disorders have also been linked to various psychiatric illnesses such as depression, anxiety, substance abuse, autism spectrum disorder, and eating disorders. It is hypothesized that techniques aimed at strengthening and repopulating the gut microbiome, such as Fecal Microbiota Transplant (FMT), may be useful in the prevention and treatment of psychiatric illnesses.<br><br>METHODS: A systematic search of five databases was conducted using key terms related to FMT and psychiatric illnesses. All results were then evaluated based on specific eligibility criteria.<br><br>RESULTS: Twenty-one studies met the eligibility criteria and were analysed for reported changes in mood and behavioural measures indicative of psychiatric wellbeing. The studies included were either entirely clinical (n&#x2009;=&#x2009;8), preclinical with human donors (n&#x2009;=&#x2009;9), or entirely preclinical (n&#x2009;=&#x2009;11). All studies found a decrease in depressive and anxiety-like symptoms and behaviours resulting from the transplantation of healthy microbiota. The inverse was also found, with the transmission of depressive and anxiety-like symptoms and behaviours resulting from the transplantation of microbiota from psychiatrically ill donors to healthy recipients.<br><br>CONCLUSION: There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT. Further research with larger sample sizes and stronger scientific design is warranted in order to fully determine the efficacy and safety of this potential treatment. Registered on PROSPERO, IRD: CRD42019126795.}, }
@article {pmid32537834, year = {2020}, author = {Li, P and Ma, X and Jin, W and Li, X and Hu, J and Jiang, X and Guo, X}, title = {Effects of local injection and intravenous injection of allogeneic bone marrow mesenchymal stem cells on the structure and function of damaged anal sphincter in rats.}, journal = {Journal of tissue engineering and regenerative medicine}, volume = {14}, number = {7}, pages = {989-1000}, doi = {10.1002/term.3079}, pmid = {32537834}, issn = {1932-7005}, mesh = {Allografts ; Animals ; Bone Marrow Cells/*immunology ; Female ; Injections, Intravenous ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*immunology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Anal sphincter injury leads to damage to the anal structure and functions and has been identified as a major risk factor for fecal incontinence. Bone marrow mesenchymal stem cells (BMSCs) with capacities of multidifferentiation, paracrine, and low immunogenicity have been widely used in tissue repair and regeneration. The primary objective of this research was to compare the effects of different injection therapies of BMSCs on the injured anal sphincters. Ninety-six Sprague-Dawley female rats were randomly divided into four groups (n = 24 each): intravenous injection, local injection, sham operation, and normal control. For the first three groups, 25% removal of the anal sphincter complex was performed and 0.3-ml phosphate-buffered saline (PBS) (containing 10[7] green fluorescent protein-labeled allogeneic BMSCs) was given accordingly to the treatment group 24 h after operation for 7 consecutive days. The sham operation group was injected with 0.3-ml PBS only. All cases had undergone evaluation in the 1st, 7th, 14th, and 28th postoperative days. The rats were sacrificed on the 28th postoperative day, and the anal sphincters were dissected to be analyzed by morphological examination. At 14 days postoperatively, local injection of BMSC significantly improved the peak contraction pressure, electromyography amplitude, and frequency of the injured anal sphincter compared with tail vein, but there was no significant difference in resting pressure until 28 days after sphincterectomy. Masson staining results confirmed that the local injection group had significantly more new muscles on the wound. BMSC could remarkably improve peak contraction pressure, electromyography amplitude, and muscle fibers on the wound, and local injection is superior to intravenous injection.}, }
@article {pmid32537754, year = {2020}, author = {Wong, SH and Yu, J}, title = {Proton-pump inhibitor use before fecal microbiota transplant: A wonder drug, a necessary evil, or a needless prescription?.}, journal = {Journal of gastroenterology and hepatology}, volume = {35}, number = {6}, pages = {913-914}, doi = {10.1111/jgh.15103}, pmid = {32537754}, issn = {1440-1746}, mesh = {Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Proton Pump Inhibitors/*administration &amp; dosage/*adverse effects ; Recurrence ; *Unnecessary Procedures ; }, }
@article {pmid32535631, year = {2020}, author = {Uchiyama, K and Wakino, S and Irie, J and Miyamoto, J and Matsui, A and Tajima, T and Itoh, T and Oshima, Y and Yoshifuji, A and Kimura, I and Itoh, H}, title = {Contribution of uremic dysbiosis to insulin resistance and sarcopenia.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {35}, number = {9}, pages = {1501-1517}, doi = {10.1093/ndt/gfaa076}, pmid = {32535631}, issn = {1460-2385}, mesh = {Animals ; Bacteria/*isolation &amp; purification ; Dysbiosis/*complications/microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Insulin Resistance ; Lipids/blood ; Male ; Mice ; Mice, Inbred ICR ; Renal Insufficiency, Chronic/*physiopathology ; Sarcopenia/*etiology/pathology/therapy ; Uremia/*complications ; }, abstract = {BACKGROUND: Chronic kidney disease (CKD) leads to insulin resistance (IR) and sarcopenia, which are associated with a high mortality risk in CKD patients; however, their pathophysiologies remain unclear. Recently, alterations in gut microbiota have been reported to be associated with CKD. We aimed to determine whether uremic dysbiosis contributes to CKD-associated IR and sarcopenia.<br><br>METHODS: CKD was induced in specific pathogen-free mice via an adenine-containing diet; control animals were fed a normal diet. Fecal microbiota transplantation (FMT) was performed by oral gavage in healthy germ-free mice using cecal bacterial samples obtained from either control mice (control-FMT) or CKD mice (CKD-FMT). Vehicle mice were gavaged with sterile phosphate-buffered saline. Two weeks after inoculation, mice phenotypes, including IR and sarcopenia, were evaluated.<br><br>RESULTS: IR and sarcopenia were evident in CKD mice compared with control mice. These features were reproduced in CKD-FMT mice compared with control-FMT and vehicle mice with attenuated insulin-induced signal transduction and mitochondrial dysfunction in skeletal muscles. Intestinal tight junction protein expression and adipocyte sizes were lower in CKD-FMT mice than in control-FMT mice. Furthermore, CKD-FMT mice showed systemic microinflammation, increased concentrations of serum uremic solutes, fecal bacterial fermentation products and elevated lipid content in skeletal muscle. The differences in gut microbiota between CKD and control mice were mostly consistent between CKD-FMT and control-FMT mice.<br><br>CONCLUSIONS: Uremic dysbiosis induces IR and sarcopenia, leaky gut and lipodystrophy.}, }
@article {pmid32535405, year = {2020}, author = {Liu, L and Wang, Q and Wu, X and Qi, H and Das, R and Lin, H and Shi, J and Wang, S and Yang, J and Xue, Y and Mao, D and Luo, Y}, title = {Vancomycin exposure caused opportunistic pathogens bloom in intestinal microbiome by simulator of the human intestinal microbial ecosystem (SHIME).}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {265}, number = {Pt B}, pages = {114399}, doi = {10.1016/j.envpol.2020.114399}, pmid = {32535405}, issn = {1873-6424}, mesh = {Dysbiosis ; Ecosystem ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Vancomycin ; }, abstract = {Antibiotics are emerging organic pollutants posing high health risks to humans by causing human intestinal microbial disorders with increasing abundances of opportunistic pathogens, and fecal microbiota transplantation (FMT) has been confirmed to restore the dysbiosis of gut flora in many kinds of intestinal disease. However, to date, few studies have focused on the bloomed opportunistic pathogens associated human disease-related pathways as well as antibiotic resistance genes (ARGs) after vancomycin exposure, and there is limited information on using FMT for restoration of intestinal microbiome affected by antibiotics. Therefore, this study investigated effects of vancomycin on the opportunistic pathogens, human disease-related pathways as well as ARGs in human gut, and the restoration of intestinal microbiome by FMT. Results indicated that vancomycin treatment substantially increased human disease-related pathways and decreased abundances of ARGs. Besides, the bloomed opportunistic pathogens including Achromobacter, Klebsiella, and Pseudomonas, caused by vancomycin exposure, were positively correlated with human disease-related pathways. The microbiota abundance and genes of human disease-related pathways and antibiotic resistance showed a remarkable return towards baseline after FMT, but not for natural recovery. These findings suggest that impacts of vancomycin on human gut are profound and FMT will be a promising strategy in clinical application that can restore the dysbiosis of gut microbiota, which may be valuable for directing future work.}, }
@article {pmid32532320, year = {2020}, author = {Thurner, M and Deutsch, M and Janke, K and Messner, F and Kreutzer, C and Beyl, S and Couillard-Després, S and Hering, S and Troppmair, J and Marksteiner, R}, title = {Generation of myogenic progenitor cell-derived smooth muscle cells for sphincter regeneration.}, journal = {Stem cell research &amp; therapy}, volume = {11}, number = {1}, pages = {233}, pmid = {32532320}, issn = {1757-6512}, support = {P 27729/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; Cell Differentiation ; Cells, Cultured ; Mice ; *Muscle Development ; Muscle, Skeletal ; Myoblasts ; Myocytes, Smooth Muscle ; *Stem Cells ; }, abstract = {BACKGROUND: Degeneration of smooth muscles in sphincters can cause debilitating diseases such as fecal incontinence. Skeletal muscle-derived cells have been effectively used in clinics for the regeneration of the skeletal muscle sphincters, such as the external anal or urinary sphincter. However, little is known about the in vitro smooth muscle differentiation potential and in vivo regenerative potential of skeletal muscle-derived cells.<br><br>METHODS: Myogenic progenitor cells (MPC) were isolated from the skeletal muscle and analyzed by flow cytometry and in vitro differentiation assays. The differentiation of MPC to smooth muscle cells (MPC-SMC) was evaluated by immunofluorescence, flow cytometry, patch-clamp, collagen contraction, and microarray gene expression analysis. In vivo engraftment of MPC-SMC was monitored by transplanting reporter protein-expressing cells into the pyloric sphincter of immunodeficient mice.<br><br>RESULTS: MPC derived from human skeletal muscle expressed mesenchymal surface markers and exhibit skeletal myogenic differentiation potential in vitro. In contrast, they lack hematopoietic surface marker, as well as adipogenic, osteogenic, and chondrogenic differentiation potential in vitro. Cultivation of MPC in smooth muscle differentiation medium significantly increases the fraction of alpha smooth muscle actin (aSMA) and smoothelin-positive cells, while leaving the number of desmin-positive cells unchanged. Smooth muscle-differentiated MPC (MPC-SMC) exhibit increased expression of smooth muscle-related genes, significantly enhanced numbers of CD146- and CD49a-positive cells, and in vitro contractility and express functional Cav and Kv channels. MPC to MPC-SMC differentiation was also accompanied by a reduction in their skeletal muscle differentiation potential. Upon removal of the smooth muscle differentiation medium, a major fraction of MPC-SMC remained positive for aSMA, suggesting the definitive acquisition of their phenotype. Transplantation of murine MPC-SMC into the mouse pyloric sphincter revealed engraftment of MPC-SMC based on aSMA protein expression within the host smooth muscle tissue.<br><br>CONCLUSIONS: Our work confirms the ability of MPC to give rise to smooth muscle cells (MPC-SMC) with a well-defined and stable phenotype. Moreover, the engraftment of in vitro-differentiated murine MPC-SMC into the pyloric sphincter in vivo underscores the potential of this cell population as a novel cell therapeutic treatment for smooth muscle regeneration of sphincters.}, }
@article {pmid32529941, year = {2020}, author = {Li, X and He, C and Li, N and Ding, L and Chen, H and Wan, J and Yang, X and Xia, L and He, W and Xiong, H and Shu, X and Zhu, Y and Lu, N}, title = {The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1774-1789}, pmid = {32529941}, issn = {1949-0984}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome/drug effects ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*metabolism ; Pancreatitis/drug therapy/*metabolism/*microbiology/pathology ; Severity of Illness Index ; }, abstract = {Early dysbiosis of the gut microbiota is associated with the severity of acute pancreatitis (AP), although the underlying mechanism is unclear. Here, we investigated the role of crosstalk between NLRP3 and the gut microbiota in the development of AP utilizing gut microbiota deficient mice, as well as NLRP3 knockout (KO) mouse models. Pancreatic damage and systemic inflammation were improved in antibiotic-treated (Abx) and germ-free (GF) mice, accompanied by weakened activity of the intestinal NLRP3 inflammasome. Interestingly, fecal microbiota transplantation (FMT) reactivated the intestinal NLRP3 inflammasome and exacerbated the disease in Abx and GF mice. Although the gut barrier in GF and Abx mice was disrupted, gut microbiota deficiency ameliorated the severity of AP, probably due to the reduction in bacterial translocation from the gut to the pancreas. The composition of the gut microbiota was significantly different between NLRP3 KO mice and wild-type (WT) mice at baseline, and there were alterations in response to the induction of AP. While a dramatic shift in the gut microbiota with overgrowth of Escherichia-Shigella was observed in WT mice suffering from AP, there was no significant change in NLRP3 KO mice with or without AP, suggesting that NLRP3 deficiency counteracts AP-induced microbial disturbance. With a strengthened gut barrier and decreased systemic inflammation, NLRP3 KO mice showed less severe AP, as revealed by reduced pancreatic neutrophilic infiltration and necrosis. Taken together, these results identified the bidirectional modulation between the gut microbiota and NLRP3 in the progression of AP, which suggests the interplay of the host and microbiome during AP.}, }
@article {pmid32527171, year = {2020}, author = {Biernat, MM and Urbaniak-Kujda, D and Dybko, J and Kapelko-Słowik, K and Prajs, I and Wróbel, T}, title = {Fecal microbiota transplantation in the treatment of intestinal steroid-resistant graft-versus-host disease: two case reports and a review of the literature.}, journal = {The Journal of international medical research}, volume = {48}, number = {6}, pages = {300060520925693}, pmid = {32527171}, issn = {1473-2300}, mesh = {Adult ; Biopsy ; Drug Resistance ; Dysbiosis/immunology/microbiology/pathology/*therapy ; Fatal Outcome ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/immunology ; Glucocorticoids/*pharmacology/therapeutic use ; Graft vs Host Disease/immunology/microbiology/pathology/*therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Intestinal Mucosa/immunology/microbiology/pathology ; Leukemia, Myeloid, Acute/immunology/therapy ; Male ; Primary Myelofibrosis/immunology/therapy ; Transplantation, Homologous/adverse effects ; Treatment Outcome ; }, abstract = {Acute graft-versus-host disease (aGvHD) reduces the efficiency and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, attempts have been made to transplant fecal microbiota from healthy donors to treat intestinal GvHD. This study presented two cases of patients undergoing allo-HSCT who were later selected for fecal microbiota transplantation (FMT). In the first patient, FMT resulted in the complete resolution of symptoms, whereas therapeutic efficacy was not achieved in the second patient. FMT eliminated drug-resistant pathogens, namely very drug-resistant Enterococcus spp., but not multidrug-resistant Acinetobacter baumannii or Candida spp. Further research is needed, particularly on the safety of FMT in patients with intestinal steroid-resistant GvHD and on the distant impact of transplanted microflora on the outcomes of allo-HSCT. FMT appears promising for the treatment of patients with steroid-resistant GvHD.}, }
@article {pmid32523094, year = {2020}, author = {Pérez-Matute, P and Íñiguez, M and de Toro, M and Recio-Fernández, E and Oteo, JA}, title = {Autologous fecal transplantation from a lean state potentiates caloric restriction effects on body weight and adiposity in obese mice.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9388}, pmid = {32523094}, issn = {2045-2322}, mesh = {Adiposity ; Animals ; Body Weight ; Caloric Restriction ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/microbiology/*therapy ; Transplantation, Autologous ; }, abstract = {Autologous fecal transplantation (FT-A) emerges as a promising strategy to modulate gut microbiota with minimal side effects since individual´s own feces are transplanted. With the premise of improving obesity and its associated disorders, we investigated if fecal microbiota transplantation (FMT), heterologous and autologous, potentiates the effects of a moderate caloric restriction (CR) in high-fat diet (HFD)-induced obese mice. Mice were randomized into control, HFD, CR (12 weeks on HFD and 6 weeks under CR), FT-H (similar to CR and FMT carried out with feces from controls, weeks 17 &amp; 18), and FT-A (administration of their own feces before developing obesity at weeks 17 &amp; 18). Our study demonstrated that FMT, and, especially, FT-A potentiates the effects of a moderate CR on weight loss and adiposity in the short term, by decreasing feed efficiency and increasing adipose tissue lipolysis. Although FT-A produced a significant increase in bacterial richness/diversity, FMT did not significantly modify gut microbiota composition compared to the CR at phyla and bacteria genera levels, and only significant increases in Bifidobacterium and Blautia genera were observed. These results could suggest that other mechanisms different from bacterial microbiota engraftment participates in these beneficial effects. Thus, FT-A represents a very positive synergetic approach for obese patients that do not respond well to moderate restrictive diets.}, }
@article {pmid32519746, year = {2020}, author = {Su, X and Zhao, Y and Li, Y and Ma, S and Wang, Z}, title = {Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis.}, journal = {Clinical science (London, England : 1979)}, volume = {134}, number = {12}, pages = {1521-1535}, doi = {10.1042/CS20200475}, pmid = {32519746}, issn = {1470-8736}, mesh = {Adult ; Animals ; Case-Control Studies ; Dysbiosis/*complications ; Fatty Acids/metabolism ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*pathology ; Humans ; Hypothyroidism/*complications ; Male ; Metagenomics ; Mice, Inbred BALB C ; Phylogeny ; ROC Curve ; Thyroid Gland/*pathology ; }, abstract = {Background Previous studies have shown that the gut microbiome is associated with thyroid diseases, including Graves' disease, Hashimoto's disease, thyroid nodules, and thyroid cancer. However, the association between intestinal flora and primary hypothyroidism remains elusive. We aimed to characterize gut microbiome in primary hypothyroidism patients. Methods Fifty-two primary hypothyroidism patients and 40 healthy controls were recruited. The differences in gut microbiota between the two groups were analyzed by 16S rRNA sequencing technology. Fecal microbiota transplantation (FMT) was performed in mice using flora from both groups; changes in thyroid function were then assessed in the mice. Results There were significant differences in α and β diversities of gut microbiota between primary hypothyroidism patients and healthy individuals. The random forest analysis indicated that four intestinal bacteria (Veillonella, Paraprevotella, Neisseria, and Rheinheimera) could distinguish untreated primary hypothyroidism patients from healthy individuals with the highest accuracy; this was confirmed by receiver operator characteristic curve analysis. The short chain fatty acid producing ability of the primary hypothyroidism patients' gut was significantly decreased, which resulted in the increased serum lipopolysaccharide (LPS) levels. The FMT showed that mice receiving the transplant from primary hypothyroidism patients displayed decreased total thyroxine levels. Conclusions Our study suggests that primary hypothyroidism causes changes in gut microbiome. In turn, an altered flora can affect thyroid function in mice. These findings could help understand the development of primary hypothyroidism and might be further used to develop potential probiotics to facilitate the adjuvant treatment of this disease.}, }
@article {pmid32519440, year = {2020}, author = {Cao, X and Han, Y and Gu, M and Du, H and Song, M and Zhu, X and Ma, G and Pan, C and Wang, W and Zhao, E and Goulette, T and Yuan, B and Zhang, G and Xiao, H}, title = {Foodborne Titanium Dioxide Nanoparticles Induce Stronger Adverse Effects in Obese Mice than Non-Obese Mice: Gut Microbiota Dysbiosis, Colonic Inflammation, and Proteome Alterations.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {16}, number = {36}, pages = {e2001858}, doi = {10.1002/smll.202001858}, pmid = {32519440}, issn = {1613-6829}, mesh = {Animals ; *Colon/drug effects ; *Dysbiosis/chemically induced ; Food Contamination ; *Gastrointestinal Microbiome/drug effects ; Inflammation/chemically induced ; *Metal Nanoparticles/toxicity ; Mice ; Mice, Obese ; *Proteome/drug effects ; Proteomics ; *Titanium/toxicity ; }, abstract = {The recent ban of titanium dioxide (TiO2) as a food additive (E171) in France intensified the controversy on safety of foodborne-TiO2 nanoparticles (NPs). This study determines the biological effects of TiO2 NPs and TiO2 (E171) in obese and non-obese mice. Oral consumption (0.1 wt% in diet for 8 weeks) of TiO2 (E171, 112 nm) and TiO2 NPs (33 nm) does not cause severe toxicity in mice, but significantly alters composition of gut microbiota, for example, increased abundance of Firmicutes phylum and decreased abundance of Bacteroidetes phylum and Bifidobacterium and Lactobacillus genera, which are accompanied by decreased cecal levels of short-chain fatty acids. Both TiO2 (E171) and TiO2 NPs increase abundance of pro-inflammatory immune cells and cytokines in the colonic mucosa, indicating an inflammatory state. Importantly, TiO2 NPs cause stronger colonic inflammation than TiO2 (E171), and obese mice are more susceptible to the effects. A microbiota transplant study demonstrates that altered fecal microbiota by TiO2 NPs directly mediate inflammatory responses in the mouse colon. Furthermore, proteomic analysis shows that TiO2 NPs cause more alterations in multiple pathways in the liver and colon of obese mice than non-obese mice. This study provides important information on the health effects of foodborne inorganic nanoparticles.}, }
@article {pmid32518854, year = {2020}, author = {Kates, AE and Gaulke, I and De Wolfe, T and Zimbric, M and Haight, K and Watson, L and Suen, G and Kim, K and Safdar, N}, title = {Fecal microbiota transplantation for patients on antibiotic treatment with C. difficile infection history (GRAFT): Study protocol for a phase II, randomized, double-blind, placebo-controlled trial to prevent recurrent C. difficile infections.}, journal = {Contemporary clinical trials communications}, volume = {18}, number = {}, pages = {100576}, pmid = {32518854}, issn = {2451-8654}, support = {R03 HS025257/HS/AHRQ HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; }, abstract = {Recurrent Clostridiodes difficile infections (rCDIs) are a burdensome problem. Patients with a history of CDI that are prescribed antibiotics are at a high risk for recurrence. Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for rCDI, though there is little information on the impact of FMT with antibiotics on the gut microbiome. We are conducting a clinical trial of FMT to prevent rCDI in patients with a history of CDI currently taking antibiotics. Our primary objective is to determine the effect of FMT on the gut microbiome during antibiotic exposure. Our secondary aim is to assess safety and feasibility of using FMT as a prophylaxis for CDI. We plan to enroll 30 patients into a phase II randomized, double-blind, placebo-controlled trial with three arms: (1) 5 FMT capsules per day during antibiotic treatment and for 7 days post antibiotic cessation, (2) a one-time dose of 30 FMT capsules 48-72 h post cessation of antibiotic treatment, or (3) 5 placebo capsules per day during antibiotic treatment and for 7 days post antibiotic treatment. Patients provide stool samples throughout the duration of the study and are cultured C. difficile. Sequencing of the V4 region of the 16S rRNA gene will be carried out to assess the gut microbiota. Results of this study will provide information on the impact of FMT on the gut microbiome as well as the necessary data to examine whether or not prophylactic FMT should be explored further as a way to prevent CDI recurrence.}, }
@article {pmid32517023, year = {2020}, author = {Bibbò, S and Settanni, CR and Porcari, S and Bocchino, E and Ianiro, G and Cammarota, G and Gasbarrini, A}, title = {Fecal Microbiota Transplantation: Screening and Selection to Choose the Optimal Donor.}, journal = {Journal of clinical medicine}, volume = {9}, number = {6}, pages = {}, pmid = {32517023}, issn = {2077-0383}, abstract = {In the past decade, fecal microbiota transplantation (FMT) has rapidly spread worldwide in clinical practice as a highly effective treatment option against recurrent Clostridioides difficile infection. Moreover, new evidence also supports a role for FMT in other conditions, such as inflammatory bowel disease, functional gastrointestinal disorders, or metabolic disorders. Recently, some studies have identified specific microbial characteristics associated with clinical improvement after FMT, in different disorders, paving the way for a microbiota-based precision medicine approach. Moreover, donor screening has become increasingly more complex over years, along with standardization of FMT and the increasing number of stool banks. In this narrative review, we discuss most recent evidence on the screening and selection of the stool donor, with reference to recent studies that have identified specific microbiological features for clinical conditions such as Clostridioides difficile infection, irritable bowel syndrome, inflammatory bowel disease, and metabolic disorders.}, }
@article {pmid32516027, year = {2020}, author = {Zoll, J and Read, MN and Heywood, SE and Estevez, E and Marshall, JPS and Kammoun, HL and Allen, TL and Holmes, AJ and Febbraio, MA and Henstridge, DC}, title = {Fecal microbiota transplantation from high caloric-fed donors alters glucose metabolism in recipient mice, independently of adiposity or exercise status.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {319}, number = {1}, pages = {E203-E216}, doi = {10.1152/ajpendo.00037.2020}, pmid = {32516027}, issn = {1522-1555}, mesh = {Adiposity ; Animals ; *Diet, High-Fat ; *Dietary Sucrose ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Glucose/metabolism ; Glucose Intolerance/metabolism/*microbiology ; Male ; Mice ; Obesity/metabolism/*microbiology ; *Physical Conditioning, Animal ; Random Allocation ; *Sedentary Behavior ; }, abstract = {Studies suggest the gut microbiota contributes to the development of obesity and metabolic syndrome. Exercise alters microbiota composition and diversity and is protective of these maladies. We tested whether the protective metabolic effects of exercise are mediated through fecal components through assessment of body composition and metabolism in recipients of fecal microbiota transplantation (FMT) from exercise-trained (ET) mice fed normal or high-energy diets. Donor C57BL/6J mice were fed a chow or high-fat, high-sucrose diet (HFHS) for 4 wk to induce obesity and glucose intolerance. Mice were divided into sedentary (Sed) or ET groups (6 wk treadmill-based ET) while maintaining their diets, resulting in four donor groups: chow sedentary (NC-Sed) or ET (NC-ET) and HFHS sedentary (HFHS-Sed) or ET (HFHS-ET). Chow-fed recipient mice were gavaged with feces from the respective donor groups weekly, creating four groups (NC-Sed-R, NC-ET-R, HFHS-Sed-R, HFHS-ET-R), and body composition and metabolism were assessed. The HFHS diet led to glucose intolerance and obesity in the donors, whereas exercise training (ET) restrained adiposity and improved glucose tolerance. No donor group FMT altered recipient body composition. Despite unaltered adiposity, glucose levels were disrupted when challenged in mice receiving feces from HFHS-fed donors, irrespective of donor-ET status, with a decrease in insulin-stimulated glucose clearance into white adipose tissue and large intestine and specific changes in the recipient's microbiota composition observed. FMT can transmit HFHS-induced disrupted glucose metabolism to recipient mice independently of any change in adiposity. However, the protective metabolic effect of ET on glucose metabolism is not mediated through fecal factors.}, }
@article {pmid32516025, year = {2020}, author = {Satokari, R and Pietilä, L and Mattila, E and Lahtinen, P and Arkkila, PET}, title = {Faecal banking at -20 °C facilitates faecal microbiota transplantation for recurrent Clostridioides difficile infection in clinical practice.}, journal = {Infectious diseases (London, England)}, volume = {52}, number = {9}, pages = {662-665}, doi = {10.1080/23744235.2020.1774075}, pmid = {32516025}, issn = {2374-4243}, mesh = {Aged ; Aged, 80 and over ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/diagnosis/*therapy ; Colonoscopy/*methods ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Humans ; Male ; Microbiota ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, }
@article {pmid32514446, year = {2020}, author = {Carlsen, A and Omdal, R and Karlsen, L and Kvaløy, JT and Aabakken, L and Steinsbø, &#xd8; and Bolstad, N and Warren, D and Lundin, KEA and Grimstad, T}, title = {Determination of lower cut-off levels of adalimumab associated with biochemical remission in Crohn's disease.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {4}, number = {3}, pages = {410-416}, pmid = {32514446}, issn = {2397-9070}, abstract = {BACKGROUND AND AIM: Adalimumab is administered and dosed using a standardized treatment regimen. Although therapeutic drug monitoring (TDM) may help optimize treatment efficacy, the lower cut-off concentration of adalimumab needed to retain disease remission has not been established. This cross-sectional study of patients with Crohn's disease on stable medication aimed to determine a lower therapeutic drug concentration threshold of adalimumab associated with biochemical disease remission.<br><br>METHODS: C-reactive protein (CRP) and fecal calprotectin were used as established markers and albumin as an explorative marker of disease activity. Time since introduction, treatment interval, drug dosage, serum drug concentration and antidrug antibodies, disease duration, age, and sex were recorded.<br><br>RESULTS: The study included 101 patients who were divided into "active disease" and "remission" groups for inflammatory markers based on cut-off levels of 5 mg/L for CRP and 50&#x2009;mg/kg for fecal calprotectin. Cut-off levels for albumin of 36.5 and 41.5 g/L were also added as further indicatives of remission. Receiver operating characteristic analysis found optimal thresholds for adalimumab associated with remission at 6.8-7.0 mg/L for the combination of CRP and fecal calprotectin and when combining CRP, fecal calprotectin, and albumin.<br><br>CONCLUSIONS: In patients with Crohn's disease, serum adalimumab of at least 6.8 mg/L was associated with biochemical disease remission based on CRP and fecal calprotectin, supporting the use of TDM to ensure disease control. Albumin should be further tested in this setting.}, }
@article {pmid32514151, year = {2020}, author = {Fong, W and Li, Q and Yu, J}, title = {Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer.}, journal = {Oncogene}, volume = {39}, number = {26}, pages = {4925-4943}, pmid = {32514151}, issn = {1476-5594}, support = {81972576//National Natural Science Foundation of China (National Science Foundation of China)/International ; }, mesh = {Colorectal Neoplasms/immunology/microbiology/*therapy ; Dysbiosis/*immunology/microbiology ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*immunology ; Humans ; Immune System/immunology/microbiology ; Prebiotics/*administration &amp; dosage ; Precision Medicine/methods ; Probiotics/*administration &amp; dosage ; Risk Factors ; }, abstract = {Research about the role of gut microbiome in colorectal cancer (CRC) is a newly emerging field of study. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of CRC. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed. Although these strategies show promising results, mechanistically by correcting microbiota composition, modulating innate immune system, enhancing gut barrier function, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells, it should be noted that they are accompanied by risks and controversies that can potentially introduce clinical complications. During bench-to-bedside translation, evaluation of risk-and-benefit ratio, as well as patient selection, should be carefully performed. In view of the individualized host response to gut microbiome intervention, developing personalized microbiome therapy may be the key to successful clinical treatment.}, }
@article {pmid32511695, year = {2021}, author = {Bar-Yoseph, H and Carasso, S and Shklar, S and Korytny, A and Even Dar, R and Daoud, H and Nassar, R and Maharshak, N and Hussein, K and Geffen, Y and Chowers, Y and Geva-Zatorsky, N and Paul, M}, title = {Oral Capsulized Fecal Microbiota Transplantation for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization With a Metagenomic Perspective.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {73}, number = {1}, pages = {e166-e175}, doi = {10.1093/cid/ciaa737}, pmid = {32511695}, issn = {1537-6591}, mesh = {*Carbapenem-Resistant Enterobacteriaceae ; *Enterobacteriaceae Infections/prevention &amp; control ; Fecal Microbiota Transplantation ; Feces ; Humans ; Metagenomics ; Prospective Studies ; }, abstract = {BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) infections lead to considerable morbidity and mortality. We assessed the potential of fecal microbiota transplantation (FMT) to eradicate CPE carriage and aimed to explain failure or success through microbiome analyses.<br><br>METHODS: In this prospective cohort study, all consenting eligible CPE carriers received oral capsulized FMT for 2 days. Primary outcome was CPE eradication at 1 month, defined by 3 consecutive negative rectal swabs, the last also negative for carbapenemase gene by polymerase chain reaction. Comprehensive metagenomics analysis of the intestinal microbiome of donors and recipients before and after FMT was performed.<br><br>RESULTS: Fifteen CPE carriers received FMT, 13 of whom completed 2 days of treatment. CPE eradication at 1 month was successful in 9/15 and 9/13, respectively. Bacterial communities showed significant changes in both beta and alpha diversity metrics among participants who achieved CPE eradication that were not observed among failures. Post-FMT samples' beta-diversity clustered according to the treatment outcome, both in taxonomy and in function. We observed a significant decrease in beta diversity in participants who received post-FMT antibiotics. Enterobacteriaceae abundance decreased in post-FMT samples of the responders but increased among failures. Functionally, a clear demarcation between responders (who were similar to the donors) and failures was shown, driven by antimicrobial resistance genes.<br><br>CONCLUSIONS: Our study provides the biological explanation for the effect of FMT against CPE carriage. Decolonization of CPE by FMT is likely mediated by compositional and functional shifts in the microbiome. Thus, FMT might be an efficient strategy for sustained CPE eradication.<br><br>CLINICAL TRIALS REGISTRATION: NCT03167398.}, }
@article {pmid32509162, year = {2020}, author = {Wang, H and Zhou, C and Huang, J and Kuai, X and Shao, X}, title = {The potential therapeutic role of Lactobacillus reuteri for treatment of inflammatory bowel disease.}, journal = {American journal of translational research}, volume = {12}, number = {5}, pages = {1569-1583}, pmid = {32509162}, issn = {1943-8141}, abstract = {Inflammatory bowel disease (IBD) is a chronic intestinal disease of unknown etiology. However, recent studies have established a pathological role of disordered intestinal microbiota and immune dysregulation. Clinical studies have suggested that the reconstruction of the normal intestinal flora in patients with IBD can reverse the dysbiosis caused by genetic, environmental, dietary, or antibiotic factors to ameliorate the symptoms of IBD. Lactobacillus reuteri is widely present in the intestines of healthy individuals and regulates the intestinal immune system, reducing inflammation through multiple mechanisms. This review summarizes the current knowledge of the role of L. reuteri in maintaining intestinal homeostasis and considers its possible value as a new therapeutic agent for patients with IBD.}, }
@article {pmid32508773, year = {2020}, author = {Liu, H and Wang, HH}, title = {Impact of Microbiota Transplant on Resistome of Gut Microbiota in Gnotobiotic Piglets and Human Subjects.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {932}, pmid = {32508773}, issn = {1664-302X}, abstract = {Microbiota transplant is becoming a popular process to restore or initiate "healthy" gut microbiota and immunity. But, the potential risks of the related practices need to be carefully evaluated. This study retrospectively examined the resistomes of donated fecal microbiota for treating intestinal disorders, vaginal microbiota of pregnant women, and infant fecal microbiota from rural and urban communities, as well as the impact of transplants on the fecal resistome of human and animal recipients. Antibiotic resistance (AR) genes were found to be abundant in all donor microbiota. An overall surge of resistomes with higher prevalence and abundance of AR genes was observed in the feces of all transplanted gnotobiotic pigs as well as in the feces of infant subjects, compared to those in donor fecal and maternal vaginal microbiota. Surprisingly, transplants using rural Amish microbiota led to more instead of less AR genes in the fecal microbiota of gnotobiotic pigs than did transplants using urban microbiota. New AR gene subtypes undetected originally also appeared in gnotobiotic pigs, in Crohn's Disease (CD) patients after transplant, and in feces of infant subjects. The data illustrated the key role of the host gastrointestinal tract system in amplifying the ever-increasing AR gene pool, even without antibiotic exposure. The data further suggest that the current approaches of microbiota transplant can introduce significant health risk factor(s) to the recipients, and newborn human and animal hosts with naïve gut microbiota were especially susceptible. Given the illustrated public health risks of microbiota transplant, minimizing massive and unnecessary damages to gut microbiota by oral antibiotics and other gut impacting drugs becomes important. Since eliminating risk factors including AR bacteria and opportunistic pathogens directly from donor microbiota is still difficult to achieve, developing microbial cocktails with defined organisms and functions has further become an urgent need, should microbiota transplantation become necessary.}, }
@article {pmid32504835, year = {2020}, author = {Hu, B and Ye, C and Leung, EL and Zhu, L and Hu, H and Zhang, Z and Zheng, J and Liu, H}, title = {Bletilla striata oligosaccharides improve metabolic syndrome through modulation of gut microbiota and intestinal metabolites in high fat diet-fed mice.}, journal = {Pharmacological research}, volume = {159}, number = {}, pages = {104942}, doi = {10.1016/j.phrs.2020.104942}, pmid = {32504835}, issn = {1096-1186}, mesh = {Animals ; Bacteria/*drug effects/metabolism ; Bile Acids and Salts/metabolism ; Colon/*drug effects/metabolism/microbiology/pathology ; Diet, High-Fat ; Disease Models, Animal ; Dysbiosis ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Male ; Metabolic Syndrome/metabolism/microbiology/pathology/*therapy ; Mice, Inbred C57BL ; Oligosaccharides/isolation &amp; purification/*pharmacology ; *Orchidaceae/chemistry ; Plant Extracts/isolation &amp; purification/*pharmacology ; Tryptophan/metabolism ; }, abstract = {As traditional Chinese medicine, Bletilla striata has been widely applied to clinical treatment for its unique pharmacological profiles. This study aimed to investigate the beneficial role of Bletilla striata oligosaccharides (BO) in improving the metabolic syndrome by regulation of gut microbiota and intestinal metabolites. Treatment of HFD-fed mice with BO prevented weight gain, reversed the glucose intolerance and insulin resistance, and inhibited adipocyte hypertrophy. BO-treated mice also suppressed chronic inflammation and protected intestinal barrier from damage. These effects were linked to the reversal of gut microbiota dysbiosis, which contributed to the homeostasis of intestinal metabolites including bile acids, short-chain fatty acids and tryptophan catabolites. The depletion and reconstitution of intestinal flora from BO- or HFD-treated mice confirmed the significance of gut microbiota in regulation of HFD-induced metabolic disorders. We demonstrated for the first time that BO improved metabolic syndrome through the regulation of gut microbiota and intestinal metabolites. The modulation initiated by BO represents a promising strategy for treatment of obesity and related metabolic diseases.}, }
@article {pmid32504369, year = {2021}, author = {Horvath, A and Bausys, A and Sabaliauskaite, R and Stratilatovas, E and Jarmalaite, S and Schuetz, B and Stiegler, P and Bausys, R and Stadlbauer, V and Strupas, K}, title = {Distal Gastrectomy with Billroth II Reconstruction is Associated with Oralization of Gut Microbiome and Intestinal Inflammation: A Proof-of-Concept Study.}, journal = {Annals of surgical oncology}, volume = {28}, number = {2}, pages = {1198-1208}, pmid = {32504369}, issn = {1534-4681}, mesh = {Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Cross-Sectional Studies ; Female ; Gastrectomy ; *Gastroenterostomy ; *Gastrointestinal Microbiome ; Humans ; Inflammation/etiology ; Male ; Quality of Life ; }, abstract = {BACKGROUND: Subtotal gastrectomy with Billroth II reconstruction (SGB2) results in increased gastric pH and diminished gastric barrier. Increased gastric pH following PPI therapy has an impact on the gut microbiome, intestinal inflammation, and possibly patient health. If similar changes are present after SGB2, these can be relevant for patient health and long-term outcomes after surgery. The aim of the study is to investigate whether SGB2 is associated with specific changes in gut microbiome composition and intestinal inflammation.<br><br>PATIENTS AND METHODS: This cross-sectional proof-of-concept study includes patients after SGB2 (n&#x2009;=&#x2009;14) for early gastric cancer and their nongastrectomized in-house relatives as controls (n&#x2009;=&#x2009;8). Fecal microbiome composition, intestinal inflammation (fecal calprotectin), gut permeability (DAO, LBP, sCD14), systemic inflammation (CRP) markers, and gastrointestinal symptoms are investigated. This study is registered at ClinicalTrials.gov (NCT03418428).<br><br>RESULTS: Microbiome oralization following SGB2 was defined by an increase in Escherichia-Shigella, Enterococcus, Streptococcus, and other typical oral cavity bacteria (Veillonella, Oribacterium, and Mogibacterium) abundance. The fecal calprotectin was increased in the SGB2 group [100.9 (52.1; 292) vs. 25.8 (17; 66.5); p&#x2009;=&#x2009;0.014], and calprotectin levels positively correlated with the abundance of Streptococcus (rs&#x2009;=&#x2009;0.639; padj&#x2009;=&#x2009;0.023). Gastrointestinal symptoms in SGB2 patients were associated with distinct taxonomic changes of the gut microbiome.<br><br>CONCLUSIONS: SGB2 is associated with oralization of the gut microbiome; intestinal inflammation and microbiome changes were associated with gastrointestinal symptoms. These novel findings may open gut microbiome as a new target for therapy to improve quality of life and general patient health in long-term survivors after SGB2.}, }
@article {pmid32504332, year = {2020}, author = {Kousgaard, SJ and Nielsen, HL and Kirk, KF and Thorlacius-Ussing, O}, title = {Consumption of yoghurt favours remission after faecal microbiota transplantation for chronic pouchitis.}, journal = {International journal of colorectal disease}, volume = {35}, number = {10}, pages = {1955-1958}, pmid = {32504332}, issn = {1432-1262}, mesh = {Fecal Microbiota Transplantation ; Feces ; Humans ; Pilot Projects ; *Pouchitis/therapy ; Prospective Studies ; Yogurt ; }, abstract = {PURPOSE: The gut microbiota is conceivably a key factor in the aetiology of pouchitis. Faecal microbiota transplantation (FMT) has been suggested as a promising new treatment for chronic pouchitis, where treatment options often are few. However, little is known about the influence of the diet on the clinical effects of FMT. We assessed the diet of patients with chronic pouchitis undergoing FMT to investigate the influence of diet on the clinical outcome after FMT.<br><br>METHODS: Nine patients with chronic pouchitis were allocated to treatment with FMT delivered by enema from five faecal donors for 14 consecutive days in a 6-month prospective, open-label, single-centre cohort pilot study. A dietary questionnaire was completed at baseline for all patients and donors. Patients underwent a pouchoscopy at baseline and at 30-day follow-up, and the Pouchitis Disease Activity Index (PDAI) was assessed.<br><br>RESULTS: Patients' diets were generally similar, when comparing patients in remission post-FMT (PDAI <&#x2009;7) with those who relapsed (PDAI &#x2265;&#x2009;7). Consumption of grains trended to be different between the two groups (p&#x2009;=&#x2009;0.06), where patients in relapse consumed more bread products than did patients in remission. However, consumption of yoghurt was significantly different between the two groups (p&#x2009;=&#x2009;0.04), with patients in remission consuming more yoghurt (mean 1.1&#xa0;s/d vs 0.2&#xa0;s/d).<br><br>CONCLUSION: Gastroenterologist performing clinical studies on FMT for chronic pouchitis should be aware of dietary habits as contributing factors for the clinical effect of FMT.}, }
@article {pmid32502314, year = {2020}, author = {Giles, EM and Couper, J}, title = {Microbiome in health and disease.}, journal = {Journal of paediatrics and child health}, volume = {56}, number = {11}, pages = {1735-1738}, doi = {10.1111/jpc.14939}, pmid = {32502314}, issn = {1440-1754}, mesh = {Child ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Humans ; *Microbiota ; *Probiotics ; }, abstract = {There has been an exponential rise in research into the microbiota of the human gastrointestinal tract, particularly of the genomic content (the microbiome). The vast number of micro-organisms residing in our gut has an integral role in essential processes, including growth and development. Probiotics, live micro-organisms with putative benefits on health have become ubiquitous as treatments for many conditions, despite often limited robust clinical trial data. However, the resurgence of faecal microbial transplantation as an effective treatment modality provides further promise that manipulation of our microbiome can have clinical benefits. This review will present the recent evidence for the role of the microbiome in development and growth, and focus on the evidence for its manipulation in paediatric diseases. We will show that while there is promising data in specific diseases, there remain many unanswered questions. Only through a deeper understanding of our complex internal ecosystem will we be able to move to the next stage of targeted microbial therapy.}, }
@article {pmid32501140, year = {2020}, author = {Reygner, J and Charrueau, C and Delannoy, J and Mayeur, C and Robert, V and Cuinat, C and Meylheuc, T and Mauras, A and Augustin, J and Nicolis, I and Modoux, M and Joly, F and Waligora-Dupriet, AJ and Thomas, M and Kapel, N}, title = {Freeze-dried fecal samples are biologically active after long-lasting storage and suited to fecal microbiota transplantation in a preclinical murine model of Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {11}, number = {5}, pages = {1405-1422}, pmid = {32501140}, issn = {1949-0984}, mesh = {Administration, Oral ; Animals ; Bacteria/growth &amp; development ; Biological Specimen Banks ; Capsules ; Clostridium Infections/*therapy ; Disease Models, Animal ; Fatty Acids, Volatile/analysis ; *Fecal Microbiota Transplantation ; *Feces/chemistry/microbiology ; *Freeze Drying ; Freezing ; *Gastrointestinal Microbiome ; Germ-Free Life ; Mice ; Time Factors ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioides difficile infection. Recent studies have reported protocols using capsules of either frozen or freeze-dried stool allowing oral administration in in- and out-patient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficile properties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance of Clostridioides difficile infection in a preclinical murine model with a survival rate of 70% versus 53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment of Clostridioides difficile infection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.}, }
@article {pmid32500988, year = {2020}, author = {Piekarska, A and Panasiuk, A and Stępień, PM}, title = {Clinical practice guidelines for Clostridioides (Clostridium) difficile infection and fecal microbiota transplant protocol - recommendations of the Polish Society od Epidemiology and Infectious Diseases.}, journal = {Przeglad epidemiologiczny}, volume = {74}, number = {1}, pages = {69-87}, doi = {10.32394/pe.74.06}, pmid = {32500988}, issn = {0033-2100}, mesh = {Anti-Bacterial Agents ; Clostridioides difficile ; Clostridium Infections/epidemiology/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Microbiota ; Poland/epidemiology ; Practice Guidelines as Topic ; Treatment Outcome ; }, abstract = {Symptomatic Clostridium difficile infection (CDI) is an acute inflammatory disease of the gastrointestinal tract, manifesting in at least 3 unformed stools within 24 hours. Predicting factors for CDI include contact with medical care (mainly hospitalization), antibiotic therapy in the last 12 weeks, use of proton pump inhibitors (PPI), H2 blockers, cancer chemotherapy, especially in the neutropenia stage, gastrointestinal surgery, advanced age and concomitant chronic diseases (renal failure, liver failure, chronic inflammatory bowel disease - especially ulcerative bowel disease, cancer, HIV infection, cachexia and hypoalbuminaemia) and vitamin D deficiency. Clinical classification distinguishes three types of CDI - mild / moderate, severe, and fulminant. The principles of treatment of the first and subsequent CDI incidents depending on the clinical course are based on oral vancomycin. CDI is recurrent. The basis for treating CDI relapses is vancomycin administered orally at a dose of 4x125 mg for 10 days followed by concomitant vancomycin dose reduction therapy. The use of fecal microbiota transfer (FMT) in the treatment of CDI relapses is considered to be the most effective therapy for recurrent CDI. An indication for FMT is antibiotic-resistant C. difficile infection, regardless of the number of incidents CDI. The panel of tests recommended for a bacterial flora donor is presented in the recommendations.}, }
@article {pmid32499711, year = {2020}, author = {Cheung, MK and Yue, GGL and Chiu, PWY and Lau, CBS}, title = {A Review of the Effects of Natural Compounds, Medicinal Plants, and Mushrooms on the Gut Microbiota in Colitis and Cancer.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {744}, pmid = {32499711}, issn = {1663-9812}, abstract = {The human gastrointestinal tract harbors a diverse array of microorganisms that play fundamental roles in health and disease. Imbalance in the gut microbiota, namely dysbiosis, can lead to various diseases, including cancer and gastrointestinal tract disorders. Approaches to improve gut dysbiosis, such as dietary intervention, intake of probiotics, and fecal microbiota transplantation are emerging strategies to treat these diseases. Various medicinal botanicals have reported anti-cancer and/or anti-inflammatory properties. Preclinical studies have illustrated that some of these natural products are also capable to modulate the gut microbiota, suggesting their use as possible alternative approach to improve gut dysbiosis and thereby assist diseases treatment. In this review article, we have summarized the current knowledge on the effects of natural compounds, medicinal plants, and mushrooms on the gut microbiota in various cancers and colitis in preclinical animal models. Challenges towards the clinical use of these medicinal botanicals as modulators of the gut microbiota in cancer and colitis treatment are also discussed.}, }
@article {pmid32499569, year = {2020}, author = {Almeida, RR and Vieira, RS and Castoldi, A and Terra, FF and Melo, ACL and Canesso, MCC and Lemos, L and Cipelli, M and Rana, N and Hiyane, MI and Pearce, EL and Martins, FDS and Faria, AMC and Câmara, NOS}, title = {Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity.}, journal = {British journal of cancer}, volume = {123}, number = {4}, pages = {534-541}, pmid = {32499569}, issn = {1532-1827}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Cell Differentiation ; Cell Line, Tumor ; Dysbiosis/chemically induced/*immunology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; *Germ-Free Life ; Interleukin-4/metabolism ; Interleukin-9/*metabolism ; Male ; Melanoma/immunology/*microbiology ; Mice ; Mucous Membrane/drug effects/immunology ; Neoplasm Transplantation ; T-Lymphocytes/drug effects/*immunology ; Transforming Growth Factor beta/metabolism ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Host-microbiota interactions shape T-cell differentiation and promote tumour immunity. Although IL-9-producing T cells have been described as potent antitumour effectors, their role in microbiota-mediated tumour control remains unclear.<br><br>METHODS: We analysed the impact of the intestinal microbiota on the differentiation of colonic lamina propria IL-9-producing T cells in germ-free and dysbiotic mice. Systemic effects of the intestinal microbiota on IL-9-producing T cells and the antitumour role of IL-9 were analysed in a model of melanoma-challenged dysbiotic mice.<br><br>RESULTS: We show that germ-free mice have lower frequency of colonic lamina propria IL-9-producing T cells when compared with conventional mice, and that intestinal microbiota reconstitution restores cell frequencies. Long-term antibiotic treatment promotes host dysbiosis, diminishes intestinal IL-4 and TGF-&#x3b2; gene expression, decreases the frequency of colonic lamina propria IL-9-producing T cells, increases the susceptibility to tumour development and reduces the frequency of IL-9-producing T cells in the tumour microenvironment. Faecal transplant restores intestinal microbiota diversity, and the frequency of IL-9-producing T cells in the lungs of dysbiotic animals, restraining tumour burden. Finally, recombinant IL-9 injection enhances tumour control in dysbiotic mice.<br><br>CONCLUSIONS: Host-microbiota interactions are required for adequate differentiation and antitumour function of IL-9-producing T cells.}, }
@article {pmid32499509, year = {2020}, author = {Pensec, C and Gillaizeau, F and Guenot, D and Bessard, A and Carton, T and Leuillet, S and Campone, M and Neunlist, M and Blottière, HM and Le Vacon, F}, title = {Impact of pemetrexed chemotherapy on the gut microbiota and intestinal inflammation of patient-lung-derived tumor xenograft (PDX) mouse models.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9094}, pmid = {32499509}, issn = {2045-2322}, mesh = {Animals ; Antineoplastic Agents/*adverse effects ; Carcinoma, Non-Small-Cell Lung/*drug therapy/*microbiology/pathology ; Disease Models, Animal ; Female ; *Gastrointestinal Microbiome ; Heterografts ; Inflammation ; Intestinal Mucosa/drug effects/*microbiology/pathology ; Lung Neoplasms/*drug therapy/*microbiology/pathology ; Mice, SCID ; *Neoplasm Transplantation ; Pemetrexed/*adverse effects ; Specific Pathogen-Free Organisms ; }, abstract = {Chemotherapy remains the gold standard for advanced cancer. Pemetrexed, a chemotherapeutic agent used in non-small cell lung cancer, can induce significant side effects in patients. Although microbiota's role in the efficacy and/or toxicity of chemotherapy agents has been demonstrated, the impacts of pemetrexed on the gut microbiota and on gastrointestinal inflammation remain unknown. The objective of this study was to evaluate the impact of pemetrexed and the tumor graft on the gut microbiota composition in immunodeficient mice. The faecal microbiota composition was studied with metabarcoding before, 24-h and one week after treatment. The colon epithelial barrier integrity was evaluated by histological examination, intestinal permeability measurement, and selected cytokines quantification. The tumor graft induced some variations in the microbiota composition. Pemetrexed further increased the relative abundance of Enterobacteriaceae and 3 families from the Firmicutes phylum: Enterococcaceae, Lactobacillaceae and Streptococcaceae. Pemetrexed also significantly altered the epithelial barrier integrity, which was associated with early inflammation. This pilot study shows that the association of a lung tumor graft with pemetrexed causes an alteration in the microbiota composition. Such information increases our knowledge about the impact of chemotherapy on the microbiota, which could help to minimize side effects and improve therapeutic effectiveness in the future.}, }
@article {pmid32499362, year = {2020}, author = {Simpson, E and Sanjar, F and Wylie, D and Park, S and Koh, H and Bae, J and Kook, SY and Kim, S and Kim, HJ}, title = {Draft Genome Sequences of Two Strains of Bifidobacterium dentium Isolated from a Crude Fecal Extract Used for Fecal Microbiota Transplantation in the Republic of Korea.}, journal = {Microbiology resource announcements}, volume = {9}, number = {23}, pages = {}, pmid = {32499362}, issn = {2576-098X}, abstract = {We present the draft genome sequences of two Bifidobacterium dentium strains isolated from a fecal extract for fecal microbiota transplantation at a hospital in the Republic of Korea. Phylogenetic and functional analyses were performed to understand the physiological characteristics and functions of Bifidobacterium spp. in the human intestine.}, }
@article {pmid32496421, year = {2021}, author = {Assimakopoulos, SF and Papadopoulou, I and Bantouna, D and de Lastic, AL and Rodi, M and Mouzaki, A and Gogos, CA and Zolota, V and Maroulis, I}, title = {Fecal Microbiota Transplantation and Hydrocortisone Ameliorate Intestinal Barrier Dysfunction and Improve Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis.}, journal = {Shock (Augusta, Ga.)}, volume = {55}, number = {5}, pages = {666-675}, doi = {10.1097/SHK.0000000000001566}, pmid = {32496421}, issn = {1540-0514}, mesh = {Animals ; Cecum/surgery ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Hydrocortisone/*pharmacology/*therapeutic use ; Intestines/*drug effects/*physiology ; Ligation ; Male ; Punctures ; Random Allocation ; Rats ; Rats, Wistar ; Sepsis/etiology/mortality/*therapy ; Survival Rate ; }, abstract = {INTRODUCTION: Sepsis is a life-threatening syndrome which can progress to multiple organ dysfunction with high mortality. Intestinal barrier failure exerts a central role in the pathophysiological sequence of events that lead from sepsis to multiple organ dysfunction. The present study investigated the role of hydrocortisone (HC) administration and fecal microbiota transplantation (FMT) in several parameters of the gut barrier integrity, immune activation, and survival, in a model of polymicrobial sepsis in rats.<br><br>METHODS: Forty adults male Wistar rats were randomly divided into four groups: sham (group I), cecal ligation and puncture (CLP) (group II), CLP&#x200a;+&#x200a;HC (2.8&#x200a;mg/kg, intraperitoneally single dose at 6&#x200a;h) (group III), and CLP&#x200a;+&#x200a;FMT at 6&#x200a;h (group IV). At 24&#x200a;h post-CLP, ileal tissues were harvested for histological and immunohistochemical analyses while endotoxin, IL-6, and IL-10 levels in systemic circulation were determined. In a second experiment the same groups were observed for 7 days for mortality, with daily administration of hydrocortisone (group III) and FMT (group IV) in surviving rats.<br><br>RESULTS: HC administration and FMT significantly reduced mortality of septic rats by 50%. These interventions totally reversed intestinal mucosal atrophy by increasing villous density and mucosal thickness (&#x3bc;m, mean&#x200a;&#xb1;&#x200a;SD: Group I: 620&#x200a;&#xb1;&#x200a;35, Group II: 411&#x200a;&#xb1;&#x200a;52, Group III: 622&#x200a;&#xb1;&#x200a;19, Group IV: 617&#x200a;&#xb1;&#x200a;44). HC and FMT reduced the apoptotic body count in intestinal crypts whereas these increased the mitotic/apoptotic index. Activated caspase-3 expression in intestinal crypts was significantly reduced by HC or FMT (activated caspase-3 (+) enterocytes/10 crypts, mean&#x200a;&#xb1;&#x200a;SD: Group I: 1.6&#x200a;&#xb1;&#x200a;0.5, Group II: 5.8&#x200a;&#xb1;&#x200a;2.4, Group III: 3.6&#x200a;&#xb1;&#x200a;0.9, Group IV: 2.3&#x200a;&#xb1;&#x200a;0.6). Both treatments increased Paneth cell count and decreased intraepithelial CD3(+) T lymphocytes and inflammatory infiltration of lamina propria to control levels. In the sham group almost the total of intestinal epithelial cells expressed occludin (92&#x200a;&#xb1;&#x200a;8%) and claudin-1 (98&#x200a;&#xb1;&#x200a;4%) and CLP reduced this expression to 34&#x200a;&#xb1;&#x200a;12% for occludin and 35&#x200a;&#xb1;&#x200a;7% for claudin-1. Administration of HC significantly increased occludin (51&#x200a;&#xb1;&#x200a;17%) and claudin-1 (77&#x200a;&#xb1;&#x200a;9%) expression. FMT exerted also a significant restoring effect in tight junction by increasing occludin (56&#x200a;&#xb1;&#x200a;15%) and claudin-1 (84&#x200a;&#xb1;&#x200a;7%) expression. The beneficial effects of these treatments on gut barrier function led to significant reduction of systemic endotoxemia (EU/mL, mean&#x200a;&#xb1;&#x200a;SD: Group I: 0.93&#x200a;&#xb1;&#x200a;0.36, Group II: 2.14&#x200a;&#xb1;&#x200a;1.74, Group III: 1.48&#x200a;&#xb1;&#x200a;0.53, Group IV: 1.61&#x200a;&#xb1;&#x200a;0.58), while FMT additionally decreased IL-6 and IL-10 levels.<br><br>CONCLUSION: Fecal microbiota transplantation and stress dose hydrocortisone administration in septic rats induce a multifactorial improvement of the gut mechanical and immunological barriers, preventing endotoxemia and leading to improved survival.}, }
@article {pmid32495834, year = {2020}, author = {Rasmussen, TS and Koefoed, AK and Jakobsen, RR and Deng, L and Castro-Mejía, JL and Brunse, A and Neve, H and Vogensen, FK and Nielsen, DS}, title = {Bacteriophage-mediated manipulation of the gut microbiome - promises and presents limitations.}, journal = {FEMS microbiology reviews}, volume = {44}, number = {4}, pages = {507-521}, doi = {10.1093/femsre/fuaa020}, pmid = {32495834}, issn = {1574-6976}, mesh = {Bacteriophages/*physiology ; Diabetes Mellitus, Type 2/therapy ; Fecal Microbiota Transplantation/standards/*trends ; *Gastrointestinal Microbiome ; Humans ; Obesity/therapy ; Virome ; }, abstract = {Gut microbiome (GM) composition and function are linked to human health and disease, and routes for manipulating the GM have become an area of intense research. Due to its high treatment efficacy, the use of fecal microbiota transplantation (FMT) is generally accepted as a promising experimental treatment for patients suffering from GM imbalances (dysbiosis), e.g. caused by recurrent Clostridioides difficile infections (rCDI). Mounting evidence suggests that bacteriophages (phages) play a key role in successful FMT treatment by restoring the dysbiotic bacterial GM. As a refinement to FMT, removing the bacterial component of donor feces by sterile filtration, also referred to as fecal virome transplantation (FVT), decreases the risk of invasive infections caused by bacteria. However, eukaryotic viruses and prophage-encoded virulence factors remain a safety issue. Recent in vivo studies show how cascading effects are initiated when phage communities are transferred to the gut by e.g. FVT, which leads to changes in the GM composition, host metabolome, and improve host health such as alleviating symptoms of obesity and type-2-diabetes (T2D). In this review, we discuss the promises and limitations of FVT along with the perspectives of using FVT to treat various diseases associated with GM dysbiosis.}, }
@article {pmid32495743, year = {2020}, author = {Chinna Meyyappan, A and Milev, R}, title = {The Safety, Efficacy, and Tolerability of Microbial Ecosystem Therapeutic-2 in People With Major Depression and/or Generalized Anxiety Disorder: Protocol for a Phase 1, Open-Label Study.}, journal = {JMIR research protocols}, volume = {9}, number = {6}, pages = {e17223}, pmid = {32495743}, issn = {1929-0748}, abstract = {BACKGROUND: The bidirectional signaling between the gut microbiota and the brain, known as the gut-brain axis, is being heavily explored in current neuropsychiatric research. Analyses of the human gut microbiota have shown considerable individual variability in bacterial content, which is hypothesized to influence brain function, and potentially mood and anxiety symptoms, through gut-brain axis communication. Preclinical and clinical research examining these effects suggests that fecal microbiota transplant (FMT) may aid in improving the severity of depression and anxiety symptoms by recolonizing the gastrointestinal (GI) tract with healthy bacteria. The microbial ecosystem therapeutic (ie, microbial ecosystem therapeutic-2 [MET-2]) used in this study is an alternative treatment to FMT, which comprises 40 different strains of gut bacteria from a healthy donor.<br><br>OBJECTIVE: The primary objective of this study is to assess subjective changes in mood and anxiety symptoms before, during, and after administration of MET-2. The secondary objectives of this study are to assess the changes in metabolic functioning and the level of repopulation of healthy gut bacteria, the safety and tolerability of MET-2, and the effects of early stress on biomarkers of depression/anxiety and the response to treatment.<br><br>METHODS: Adults experiencing depressive or anxiety symptoms will be recruited from the Kingston area. These participants will orally consume an encapsulated MET-2 once daily-containing 40 strains of purified and laboratory-grown bacteria from a single healthy donor-for 8 weeks, followed by a 2-week treatment-free follow-up period. Participants will undergo a series of clinical assessments measuring mood, anxiety, and GI symptoms using validated clinical scales and questionnaires. Molecular data will be collected from blood and fecal samples to assess metabolic changes, neurotransmitter levels, inflammatory markers, and the level of engraftment of the fecal samples that may predict outcomes in depression or anxiety.<br><br>RESULTS: Given the association between the gut bacteria and the risk factors of depression, we expect to observe an improvement in the severity of depressive and anxiety symptoms following treatment, and we expect that this improvement is mediated by the recolonization of the GI tract with healthy bacteria. The recruitment for this study has been completed, and the data obtained are currently being analyzed.<br><br>CONCLUSIONS: This is the first time MET-2 is being tested in psychiatric indications, specifically depression and anxiety. As such, this may be the first study to show the potential effects of microbial therapy in alleviating psychiatric symptoms as well as its safety and tolerability.<br><br>DERR1-10.2196/17223.}, }
@article {pmid32493442, year = {2020}, author = {Trang-Poisson, C and Kerdreux, E and Poinas, A and Planche, L and Sokol, H and Bemer, P and Cabanas, K and Hivernaud, E and Biron, L and Flet, L and Montassier, E and Le Garcasson, G and Chiffoleau, A and Jobert, A and Lepelletier, D and Caillon, J and Le Pape, P and Imbert, BM and Bourreille, A}, title = {Impact of fecal microbiota transplantation on chronic recurrent pouchitis in ulcerative colitis with ileo-anal anastomosis: study protocol for a prospective, multicenter, double-blind, randomized, controlled trial.}, journal = {Trials}, volume = {21}, number = {1}, pages = {455}, pmid = {32493442}, issn = {1745-6215}, support = {16-267//Minist&#xe8;re des Affaires Sociales, de la Sant&#xe9; et des Droits des Femmes/ ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Chronic Disease ; Colitis, Ulcerative/*surgery ; Double-Blind Method ; *Fecal Microbiota Transplantation ; France ; Humans ; Multicenter Studies as Topic ; Pouchitis/etiology/*therapy ; Proctocolectomy, Restorative/*adverse effects ; Prospective Studies ; Quality of Life ; Randomized Controlled Trials as Topic ; Recurrence ; }, abstract = {BACKGROUND: Almost 15% of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch-anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available. Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UC-associated pouchitis. However, there is currently no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis.<br><br>METHODS: Our project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation.<br><br>DISCUSSION: On April 30, 2014, the World Health Organization published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT03524352. Registered on 14 May 2018.}, }
@article {pmid32492490, year = {2020}, author = {Gulati, M and Singh, SK and Corrie, L and Kaur, IP and Chandwani, L}, title = {Delivery routes for faecal microbiota transplants: Available, anticipated and aspired.}, journal = {Pharmacological research}, volume = {159}, number = {}, pages = {104954}, doi = {10.1016/j.phrs.2020.104954}, pmid = {32492490}, issn = {1096-1186}, mesh = {Animals ; Capsules ; *Cecostomy/adverse effects/instrumentation ; Dysbiosis ; *Endoscopy, Digestive System/adverse effects/instrumentation ; *Fecal Microbiota Transplantation/adverse effects/instrumentation ; Gastrointestinal Diseases/microbiology/physiopathology/*therapy ; *Gastrointestinal Microbiome ; Humans ; Treatment Outcome ; }, abstract = {Fecal microbiota transplant (FMT) has seen a historic emergence in last decade with its sojourn recently entering into a chequered path, due to a few reports of infection and subsequent mortality. Though FMT has been extensively reported, there is no comprehensive report on the delivery routes available for this non-pharmacological treatment option. Safety, efficacy and cost of FMT not only depend on the quality of contents but also on the delivery route employed. A number of delivery routes are in use for conducting FMT, which include upper gastrointestinal routes (UGI) i.e. nasogastric/nasojejunal tube, endoscopy, oral capsules and lower gastrointestinal routes (LGI) like retention enema, sigmoidoscopy or colonoscopy. Capsules, both conventional as well as colon targeted have been the most commonly used formulations. Surprisingly, the success rates with conventional gastric delivery capsules and colon targeted capsules were found to be quite similar indicating the sufficiency of the inoculum size to withstand the microbial loss in the gastric milieu. Patient compliance, cost effectiveness, comfort of administration, level of invasiveness, patient's hospital admission, risk of aspiration and infections, multiplicity of administration required, recurrence rate are the main factors that seem to influence the choice for route of administration of physicians. The best route for FMT has not been established yet. Extensive studies are required to understand the interplay of route adopted, type of donor, physical nature of sample (fresh or frozen), patient compliance and cost effectiveness to design an approach for the risk free, convenient and cost-effective administration route for FMT.}, }
@article {pmid32487252, year = {2020}, author = {Adelman, MW and Woodworth, MH and Langelier, C and Busch, LM and Kempker, JA and Kraft, CS and Martin, GS}, title = {The gut microbiome's role in the development, maintenance, and outcomes of sepsis.}, journal = {Critical care (London, England)}, volume = {24}, number = {1}, pages = {278}, pmid = {32487252}, issn = {1466-609X}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; K23AI144036//National Institute of Allergy and Infectious Diseases/International ; K08 HS025240/HS/AHRQ HHS/United States ; K08 HS-025240//Agency for Healthcare Research and Quality (US)/International ; UL1 TR-002378/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; K23 HL138461/HL/NHLBI NIH HHS/United States ; K23HL138461-01A1/HL/NHLBI NIH HHS/United States ; }, mesh = {Fecal Microbiota Transplantation/methods/*standards ; Gastrointestinal Microbiome/*immunology/physiology ; Humans ; Probiotics/therapeutic use ; Sepsis/complications/*physiopathology/*therapy ; }, abstract = {The gut microbiome regulates a number of homeostatic mechanisms in the healthy host including immune function and gut barrier protection. Loss of normal gut microbial structure and function has been associated with diseases as diverse as Clostridioides difficile infection, asthma, and epilepsy. Recent evidence has also demonstrated a link between the gut microbiome and sepsis. In this review, we focus on three key areas of the interaction between the gut microbiome and sepsis. First, prior to sepsis onset, gut microbiome alteration increases sepsis susceptibility through several mechanisms, including (a) allowing for expansion of pathogenic intestinal bacteria, (b) priming the immune system for a robust pro-inflammatory response, and (c) decreasing production of beneficial microbial products such as short-chain fatty acids. Second, once sepsis is established, gut microbiome disruption worsens and increases susceptibility to end-organ dysfunction. Third, there is limited evidence that microbiome-based therapeutics, including probiotics and selective digestive decontamination, may decrease sepsis risk and improve sepsis outcomes in select patient populations, but concerns about safety have limited uptake. Case reports of a different microbiome-based therapy, fecal microbiota transplantation, have shown correlation with gut microbial structure restoration and decreased inflammatory response, but these results require further validation. While much of the evidence linking the gut microbiome and sepsis has been established in pre-clinical studies, clinical evidence is lacking in many areas. To address this, we outline a potential research agenda for further investigating the interaction between the gut microbiome and sepsis.}, }
@article {pmid32486476, year = {2020}, author = {Okahara, K and Ishikawa, D and Nomura, K and Ito, S and Haga, K and Takahashi, M and Shibuya, T and Osada, T and Nagahara, A}, title = {Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation.}, journal = {Journal of clinical medicine}, volume = {9}, number = {6}, pages = {}, pmid = {32486476}, issn = {2077-0383}, support = {JP16K09328//Japan Society for the Promotion of Science/ ; }, abstract = {We previously demonstrated that fresh fecal microbiota transplantation (FMT) following triple antibiotic therapy (amoxicillin, fosfomycin, metronidazole (AFM); A-FMT) resulted in effective colonization of Bacteroidetes species, leading to short-term clinical response in ulcerative colitis (UC). Its long-term efficacy and criteria for donor selection are unknown. Here, we analyzed the long-term efficacy of A-FMT compared to AFM monotherapy (mono-AFM). AFM was administered to patients with mild to severe UC for 2 weeks until 2 days before fresh FMT. Clinical response and efficacy maintenance were defined by the decrease and no exacerbation in clinical activity index. The population for intention-to-treat analysis comprised 92 patients (A-FMT, n = 55; mono-AFM, n = 37). Clinical response was observed at 4 weeks post-treatment (A-FMT, 56.3%; mono-AFM, 48.6%). Maintenance rate of responders at 24 months post-treatment was significantly higher with A-FMT than mono-AFM (p = 0.034). Significant differences in maintenance rate according to the age difference between donors and patients were observed. Additionally, sibling FMT had a significantly higher maintenance rate than parent-child FMT. Microbial analysis of patients who achieved long-term maintenance showed that some exhibited similarity to their donors, particularly Bacteroidetes species. Thus, A-FMT exhibited long-term efficacy. Therefore, matching between donors and UC patients may be helpful in effectively planning the FMT regimen.}, }
@article {pmid32485921, year = {2020}, author = {Sasaki, T and Mori, S and Kishi, S and Fujiwara-Tani, R and Ohmori, H and Nishiguchi, Y and Hojo, Y and Kawahara, I and Nakashima, C and Fujii, K and Luo, Y and Kuniyasu, H}, title = {Effect of Proton Pump Inhibitors on Colorectal Cancer.}, journal = {International journal of molecular sciences}, volume = {21}, number = {11}, pages = {}, pmid = {32485921}, issn = {1422-0067}, support = {16H05164//Ministry of Education, Culture, Sports, Science and Technology/ ; 17K19923//Ministry of Education, Culture, Sports, Science and Technology/ ; 18K17726//Ministry of Education, Culture, Sports, Science and Technology/ ; 18K16671//Ministry of Education, Culture, Sports, Science and Technology/ ; 19K19332//Ministry of Education, Culture, Sports, Science and Technology/ ; 19K16564//Ministry of Education, Culture, Sports, Science and Technology/ ; 81702723//National Natural Science Foundation of China/ ; 17KJB320010//Natural Science Foundation of Jiangsu Education Department Project/ ; }, mesh = {Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Clostridium perfringens/metabolism ; Colorectal Neoplasms/*drug therapy/metabolism ; Cyclin D1/*metabolism ; Enterotoxins/chemistry ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Feces ; Gastrins/blood/metabolism ; Hydrogen-Ion Concentration ; Liver Neoplasms/secondary ; Male ; Mice ; Mice, Inbred BALB C ; Mitochondria/metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Transplantation ; Oxidative Stress ; Proton Pump Inhibitors/*pharmacology ; }, abstract = {Proton pump inhibitors (PPIs) are administered commonly to aged people; however, their effect on colorectal cancer (CRC) has still not been fully elucidated. Here, we examined the effect of PPIs and consequent alkalization on CRC cells. PPI administration alkalized the fecal pH and increased serum gastrin concentration. PPI and pH8 treatment (alkalization) of CMT93 mouse colon cancer cells inhibited cell growth and invasion, increased oxidative stress and apoptosis, and decreased mitochondrial volume and protein levels of cyclin D1 and phosphorylated extracellular signal-regulated kinase (pERK) 1/2. In contrast, gastrin treatment enhanced growth and invasion, decreased oxidative stress and apoptosis, and increased mitochondrial volume and cyclin D1 and pERK1/2 levels. Concurrent treatment with a PPI, pH8, and gastrin increased aldehyde dehydrogenase activity and also enhanced liver metastasis in the BALB/c strain of mice. PPI administration was associated with Clostridium perfringens enterotoxin (CPE) in CRC lesions. CPE treatment activated yes-associated protein (YAP) signals to enhance proliferation and stemness. The orthotopic colon cancer model of CMT93 cells with long-term PPI administration showed enhanced tumor growth and liver metastasis due to gastrin and YAP activation, as indicated by gastrin receptor knockdown and treatment with a YAP inhibitor. These findings suggest that PPI promotes CRC growth and metastasis by increasing gastrin concentration and YAP activation, resulting in gut flora alteration and fecal alkalization. These findings suggest that PPI use in colorectal cancer patients might create a risk of cancer promotion.}, }
@article {pmid32485282, year = {2020}, author = {Wang, MX and Lin, L and Chen, YD and Zhong, YP and Lin, YX and Li, P and Tian, X and Han, B and Xie, ZY and Liao, QF}, title = {Evodiamine has therapeutic efficacy in ulcerative colitis by increasing Lactobacillus acidophilus levels and acetate production.}, journal = {Pharmacological research}, volume = {159}, number = {}, pages = {104978}, doi = {10.1016/j.phrs.2020.104978}, pmid = {32485282}, issn = {1096-1186}, mesh = {Acetates/*metabolism ; Animals ; Colitis, Ulcerative/chemically induced/*drug therapy/metabolism/microbiology ; Colon/metabolism/*microbiology ; Cytokines/metabolism ; Dextran Sulfate ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Agents/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Inflammation Mediators/metabolism ; Intestinal Mucosa/metabolism/microbiology ; Lactobacillus acidophilus/*drug effects/genetics/growth &amp; development/metabolism ; Male ; Metabolomics ; Quinazolines/*pharmacology ; Rats, Sprague-Dawley ; Ribotyping ; }, abstract = {Emerging evidence implicates gut microbiota have an important role in ulcerative colitis (UC). Previous study indicated that Evodiamine (EVO) can alleviate colitis through downregulating inflammatory pathways. However, specific relationship between EVO-treated colitis relief and regulation of gut microbiota is still unclear. Here, our goal was to determine the potential role of gut microbiota in the relief of UC by EVO. By using pathology-related indicators, 16S rRNA sequencing and metabolomics profiling, we assessed the pharmacological effect of EVO on dextran sulfate sodium (DSS)-induced colitis rats as well as on the change of gut microbiota and metabolism. Fecal derived from EVO-treated rats was transplanted into colitis rats to verify the effect of EVO on gut microbiota, and 'driver bacteria' was found and validated by 16S rRNA sequencing, metagenome and qRT-PCR. The effect of Lactobacillus acidophilus (L. acidophilus) was investigated by vivo experiment, microbiota analysis, Short-chain fatty acids (SCFAs) quantification and colon transcriptomics. EVO reduced the susceptibility to DSS-induced destruction of epithelial integrity and severe inflammatory response, and regulated the gut microbiota and metabolites. Fecal Microbiota Transplantation (FMT) alleviated DSS-induced colitis, increased the abundance of L. acidophilus and the level of acetate. Furthermore, gavaged with L. acidophilus reduced pro-inflammatory cytokines, promoted the increase of goblet cells and the secretion of antimicrobial peptides, regulated the ratio of Firmicutes/Bacteroidetes and increased the level of acetate. Our results indicated that EVO mitigation of DSS-induced colitis is associated with increased in L. acidophilus and protective acetate production, which may be a promising strategy for treating UC.}, }
@article {pmid32484770, year = {2020}, author = {Zatorski, H and Nakov, R}, title = {Faecal Microbiota Transplantation in Inflammatory Bowel Disease: Current Concepts and Future Challenges.}, journal = {Current drug targets}, volume = {21}, number = {14}, pages = {1440-1447}, doi = {10.2174/1389450121666200602125507}, pmid = {32484770}, issn = {1873-5592}, support = {502-03/1-156-04/502-14-339//Medical University of Lodz/ ; }, mesh = {Animals ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Randomized Controlled Trials as Topic ; }, abstract = {Dysbiosis has been repeatedly observed in inflammatory bowel disease (IBD) and is now recognized as an essential factor in the gut inflammatory process. IBD is a significant burden to health-care systems, mainly due to treatment-related costs. Available treatments have several limitations: up to 30% of patients are primary non-responders, and between 10 and 20% lose response per year, requiring a dose-escalation or a switch to another biologic. Hence, the current IBD treatment is not sufficient, and there is an urgent need to introduce new therapies in the management of these patients. Recently, the correction of dysbiosis has become an attractive approach from a therapeutic point of view. Faecal microbiota transplantation (FMT) appears as a reliable and potentially beneficial therapy in IBD patients. There is developing data that FMT for mild-to-moderately active UC is a safe and efficient therapy for the induction of remission. However, the current studies have different designs and have a short follow up, which makes clinical interpretation significantly difficult. There is a need for RCTs with a well-defined study cohort using FMT for the therapy of CD patients. The location, behavior, and severity of the disease should be taken into account. The goal of this manuscript is to review the data currently available on FMT and IBD, to explain FMT principles and methodology in IBD patients and to discuss some unresolved issues.}, }
@article {pmid32483373, year = {2020}, author = {Burberry, A and Wells, MF and Limone, F and Couto, A and Smith, KS and Keaney, J and Gillet, G and van Gastel, N and Wang, JY and Pietilainen, O and Qian, M and Eggan, P and Cantrell, C and Mok, J and Kadiu, I and Scadden, DT and Eggan, K}, title = {C9orf72 suppresses systemic and neural inflammation induced by gut bacteria.}, journal = {Nature}, volume = {582}, number = {7810}, pages = {89-94}, pmid = {32483373}, issn = {1476-4687}, support = {R01 NS089742/NS/NINDS NIH HHS/United States ; R00 MH119327/MH/NIMH NIH HHS/United States ; 5R01NS089742/NH/NIH HHS/United States ; R00 AG057808/AG/NIA NIH HHS/United States ; P01 HL131477/HL/NHLBI NIH HHS/United States ; K99 MH119327/MH/NIMH NIH HHS/United States ; K99 AG057808/AG/NIA NIH HHS/United States ; 1K99MH119327-01/NH/NIH HHS/United States ; 5K99AG057808-02/NH/NIH HHS/United States ; }, mesh = {Animals ; Female ; Male ; Mice ; Amyotrophic Lateral Sclerosis/genetics/pathology ; Anti-Bacterial Agents/pharmacology ; Autoimmunity/drug effects/genetics/immunology ; *C9orf72 Protein/genetics ; Cell Movement/drug effects ; Cytokines/immunology ; Fecal Microbiota Transplantation ; Frontotemporal Dementia/genetics/pathology ; *Gastrointestinal Microbiome/drug effects/immunology/physiology ; *Gliosis/genetics/microbiology/pathology/prevention &amp; control ; *Inflammation/genetics/microbiology/pathology/prevention &amp; control ; Loss of Function Mutation/genetics ; Microglia/immunology/microbiology/pathology ; *Spinal Cord/immunology/microbiology/pathology ; Survival Rate ; *Brain-Gut Axis/immunology ; Disease Models, Animal ; }, abstract = {A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia[1,2]. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration[3-9]. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins[5] before its non-canonical translation into neural-toxic dipeptide proteins[3,4]. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation[6-9]. Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria[10,11] protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.}, }
@article {pmid32474615, year = {2020}, author = {Kim, M and Reibetanz, J}, title = {[Surgical reconstruction of traumatic sphincter muscle defects].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {91}, number = {10}, pages = {870-877}, doi = {10.1007/s00104-020-01206-7}, pmid = {32474615}, issn = {1433-0385}, mesh = {Anal Canal/surgery ; *Digestive System Surgical Procedures ; Fecal Incontinence/*etiology/*surgery ; Humans ; Muscle, Smooth ; *Plastic Surgery Procedures ; }, abstract = {BACKGROUND: Traumatic anal sphincter muscle defects often occur after childbirth and surgery and can lead to fecal incontinence that requires further treatment.<br><br>OBJECTIVE: The aim of this article is to illustrate the etiology of traumatic sphincter muscle defects, the treatment options of subsequent fecal incontinence and their evaluation on the basis of current studies.<br><br>MATERIAL AND METHODS: Selected studies are presented.<br><br>RESULTS: Fecal incontinence presenting with a traumatic sphincter muscle defect is often due to multiple factors especially in the aged and makes the use of extended diagnostic tools necessary; however, the subjective complaints do not always correlate with morphological or functional diagnostic findings. Besides reconstructive procedures, such as sphincteroplasty and graciloplasty, sphincter augmentation techniques and sacral nerve stimulation can also be applied in traumatic sphincter muscle defects that are often associated with a loss of efficacy in the long term or a high rate of adverse events.<br><br>CONCLUSION: The fecal incontinence associated with traumatic sphincter insufficiency represents a&#xa0;diagnostic and therapeutic challenge due to the multifactorial origin. It is not uncommon that patients have to undergo several surgical and conservative interventions.}, }
@article {pmid32474336, year = {2020}, author = {Lin, H and Wang, Q and Yuan, M and Liu, L and Chen, Z and Zhao, Y and Das, R and Duan, Y and Xu, X and Xue, Y and Luo, Y and Mao, D}, title = {The prolonged disruption of a single-course amoxicillin on mice gut microbiota and resistome, and recovery by inulin, Bifidobacterium longum and fecal microbiota transplantation.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {265}, number = {Pt A}, pages = {114651}, doi = {10.1016/j.envpol.2020.114651}, pmid = {32474336}, issn = {1873-6424}, mesh = {Amoxicillin ; Animals ; *Bifidobacterium longum ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Inulin ; Mice ; RNA, Ribosomal, 16S ; }, abstract = {The usages of antibiotics in treating the pathogenic infections could alter the gut microbiome and associated resistome, causing long term adverse impact on human health. In this study, mice were treated with human-simulated regimen 25.0 mg kg[-1] of amoxicillin for seven days, and their gut microbiota and resistome were characterized using the 16S rRNA amplicons sequencing and the high-throughput qPCR, respectively. Meanwhile, the flora restorations after individual applications of inulin, Bifidobacterium longum (B. longum), and fecal microbiota transplantation (FMT) were analyzed for up to 35 days. The results revealed the prolonged negative impact of single course AMX exposure on mice gut microbiota and resistome. To be specific, pathobionts of Klebsiella and Escherichia-Shigella were significantly enriched, while prebiotics of Bifidobacterium and Lactobacillus were dramatically depleted. Furthermore, β-lactam resistance genes and efflux resistance genes were obviously enriched after amoxicillin exposure. Compared to B. longum, FMT and inulin were demonstrated to preferably restore the gut microbiota via reconstituting microbial community and stimulating specific prebiotic respectively. Such variation of microbiome caused their distinct alleviations on resistome alteration. Inulin earned the greatest elimination on AMX induced ARG abundance and diversity enrichment. FMT and B. longum caused remove of particular ARGs such as ndm-1, blaPER. Network analysis revealed that most of the ARGs were prone to be harbored by Firmicutes and Proteobacteria. In general, gut resistome shift was partly associated with the changing bacterial community structures and transposase and integron. Taken together, these results demonstrated the profound disruption of gut microbiota and resistome after single-course amoxicillin treatment and different restoration by inulin, B. longum and FMT.}, }
@article {pmid32471482, year = {2020}, author = {Zlitni, S and Bishara, A and Moss, EL and Tkachenko, E and Kang, JB and Culver, RN and Andermann, TM and Weng, Z and Wood, C and Handy, C and Ji, HP and Batzoglou, S and Bhatt, AS}, title = {Strain-resolved microbiome sequencing reveals mobile elements that drive bacterial competition on a clinical timescale.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {50}, pmid = {32471482}, issn = {1756-994X}, support = {R01 HG006137/HG/NHGRI NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; P01 HG000205/HG/NHGRI NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; K08 CA184420/CA/NCI NIH HHS/United States ; }, mesh = {Anti-Infective Agents/pharmacology ; Azacitidine/pharmacology ; Azithromycin/pharmacology ; Bacteria/classification/drug effects/*genetics/isolation &amp; purification ; Ciprofloxacin/pharmacology ; DNA, Bacterial ; Diet ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects/*genetics ; Genome, Bacterial ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents/pharmacology ; Male ; Metagenome ; Middle Aged ; Myelodysplastic Syndromes/microbiology/therapy ; Primary Myelofibrosis/microbiology/therapy ; RNA-Seq ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Populations of closely related microbial strains can be simultaneously present in bacterial communities such as the human gut microbiome. We recently developed a de novo genome assembly approach that uses read cloud sequencing to provide more complete microbial genome drafts, enabling precise differentiation and tracking of strain-level dynamics across metagenomic samples. In this case study, we present a proof-of-concept using read cloud sequencing to describe bacterial strain diversity in the gut microbiome of one hematopoietic cell transplantation patient over a 2-month time course and highlight temporal strain variation of gut microbes during therapy. The treatment was accompanied by diet changes and administration of multiple immunosuppressants and antimicrobials.<br><br>METHODS: We conducted short-read and read cloud metagenomic sequencing of DNA extracted from four longitudinal stool samples collected during the course of treatment of one hematopoietic cell transplantation (HCT) patient. After applying read cloud metagenomic assembly to discover strain-level sequence variants in these complex microbiome samples, we performed metatranscriptomic analysis to investigate differential expression of antibiotic resistance genes. Finally, we validated predictions from the genomic and metatranscriptomic findings through in vitro antibiotic susceptibility testing and whole genome sequencing of isolates derived from the patient stool samples.<br><br>RESULTS: During the 56-day longitudinal time course that was studied, the patient's microbiome was profoundly disrupted and eventually dominated by Bacteroides caccae. Comparative analysis of B. caccae genomes obtained using read cloud sequencing together with metagenomic RNA sequencing allowed us to identify differences in substrain populations over time. Based on this, we predicted that particular mobile element integrations likely resulted in increased antibiotic resistance, which we further supported using in vitro antibiotic susceptibility testing.<br><br>CONCLUSIONS: We find read cloud assembly to be useful in identifying key structural genomic strain variants within a metagenomic sample. These strains have fluctuating relative abundance over relatively short time periods in human microbiomes. We also find specific structural genomic variations that are associated with increased antibiotic resistance over the course of clinical treatment.}, }
@article {pmid32468608, year = {2020}, author = {Kragsnaes, MS and Nilsson, AC and Kjeldsen, J and Holt, HM and Rasmussen, KF and Georgsen, J and Ellingsen, T and Holm, DK}, title = {How do I establish a stool bank for fecal microbiota transplantation within the blood- and tissue transplant service?.}, journal = {Transfusion}, volume = {60}, number = {6}, pages = {1135-1141}, doi = {10.1111/trf.15816}, pmid = {32468608}, issn = {1537-2995}, support = {//Odense University Hospital/ ; }, mesh = {*Biological Specimen Banks ; *Fecal Microbiota Transplantation ; *Feces ; Humans ; }, abstract = {Worldwide, there is a rising demand for thoroughly screened, high-quality fecal microbiota transplantation (FMT) products that can be obtained at a reasonable cost. In the light of this evolving therapeutic area of the intestinal microbiota, both private and public stool banks have emerged. However, some of the larger difficulties when establishing stool banks are caused by the absence of or international disagreement on regulation and legislative formalities. In this context, the establishment of a stool bank within a nonprofit blood and tissue transplant service has several advantages. Especially, this setting can ensure that every step of the donation process, laboratory handling, and donor-traceability is in agreement with the current expert guidelines and meets the requirements of the European Union's regulative directives on human cells and tissues. Although safety and documentation are the top priority of the stool bank setup presented here, cost-effectiveness of the production is possible due to a high donor screening success rate and the knowhow, infrastructure, facilities, personnel, and laboratory- and quality-management systems that were already in place. Overall, our experience is that a centralized, nonprofit, blood and tissue transplant service is an ideal and safe facility to run a stool bank of high quality FMT products that are based on stool donations from volunteer, unpaid, healthy, blood donors.}, }
@article {pmid32466801, year = {2020}, author = {Jian, X and Zhu, Y and Ouyang, J and Wang, Y and Lei, Q and Xia, J and Guan, Y and Zhang, J and Guo, J and He, Y and Wang, J and Li, J and Lin, J and Su, M and Li, G and Wu, M and Qiu, L and Xiang, J and Xie, L and Jia, W and Zhou, W}, title = {Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {74}, pmid = {32466801}, issn = {2049-2618}, support = {31900102//National Natural Science Foundation of China/International ; 81570205, 81630007//National Natural Science Foundation of China/International ; 81800209//National Natural Science Foundation of China/International ; 2019M652792//China Postdoctoral Science Foundation/International ; ZLXD2017004//Strategic Priority Research Program of Central South University/International ; }, mesh = {Animals ; Bacteria/genetics ; *Biodiversity ; China ; Disease Progression ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome/genetics ; Glutamine/metabolism ; *Host Microbial Interactions ; Humans ; Klebsiella/physiology ; Metagenome ; Mice ; *Multiple Myeloma/microbiology/therapy ; Streptococcus/metabolism ; }, abstract = {BACKGROUND: Gut microbiome alterations are closely related to human health and linked to a variety of diseases. Although great efforts have been made to understand the risk factors for multiple myeloma (MM), little is known about the role of the gut microbiome and alterations of its metabolic functions in the development of MM.<br><br>RESULTS: Here, in a cohort of newly diagnosed patients with MM and healthy controls (HCs), significant differences in metagenomic composition were discovered, for the first time, with higher bacterial diversity in MM. Specifically, nitrogen-recycling bacteria such as Klebsiella and Streptococcus were significantly enriched in MM. Also, the bacteria enriched in MM were significantly correlated with the host metabolome, suggesting strong metabolic interactions between microbes and the host. In addition, the MM-enriched bacteria likely result from the regulation of urea nitrogen accumulated during MM progression. Furthermore, by performing fecal microbiota transplantation (FMT) into 5TGM1 mice, we proposed a mechanistic explanation for the interaction between MM-enriched bacteria and MM progression via recycling urea nitrogen. Further experiments validated that Klebsiella pneumoniae promoted MM progression via de novo synthesis of glutamine in mice and that the mice fed with glutamine-deficient diet exhibited slower MM progression.<br><br>CONCLUSIONS: Overall, our findings unveil a novel function of the altered gut microbiome in accelerating the malignant progression of MM and open new avenues for novel treatment strategies via manipulation of the intestinal microbiota of MM patients. Video abstract.}, }
@article {pmid32466620, year = {2020}, author = {Nance, CL and Deniskin, R and Diaz, VC and Paul, M and Anvari, S and Anagnostou, A}, title = {The Role of the Microbiome in Food Allergy: A Review.}, journal = {Children (Basel, Switzerland)}, volume = {7}, number = {6}, pages = {}, pmid = {32466620}, issn = {2227-9067}, abstract = {Food allergies are common and estimated to affect 8% of children and 11% of adults in the United States. They pose a significant burden-physical, economic and social-to those affected. There is currently no available cure for food allergies. Emerging evidence suggests that the microbiome contributes to the development and manifestations of atopic disease. According to the hygiene hypothesis, children growing up with older siblings have a lower incidence of allergic disease compared with children from smaller families, due to their early exposure to microbes in the home. Research has also demonstrated that certain environmental exposures, such as a farming environment, during early life are associated with a diverse bacterial experience and reduced risk of allergic sensitization. Dysregulation in the homeostatic interaction between the host and the microbiome or gut dysbiosis appears to precede the development of food allergy, and the timing of such dysbiosis is critical. The microbiome affects food tolerance via the secretion of microbial metabolites (e.g., short chain fatty acids) and the expression of microbial cellular components. Understanding the biology of the microbiome and how it interacts with the host to maintain gut homeostasis is helpful in developing smarter therapeutic approaches. There are ongoing trials evaluating the benefits of probiotics and prebiotics, for the prevention and treatment of atopic diseases to correct the dysbiosis. However, the routine use of probiotics as an intervention for preventing allergic disease is not currently recommended. A new approach in microbial intervention is to attempt a more general modification of the gut microbiome, such as with fecal microbiota transplantation. Developing targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy. Similarly, fecal microbiota transplantation is being explored as a potentially beneficial interventional approach. Overall, targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy.}, }
@article {pmid32460890, year = {2020}, author = {Li, M and Li, C and Wu, X and Chen, T and Ren, L and Xu, B and Cao, J}, title = {Microbiota-driven interleukin-17 production provides immune protection against invasive candidiasis.}, journal = {Critical care (London, England)}, volume = {24}, number = {1}, pages = {268}, pmid = {32460890}, issn = {1466-609X}, support = {81722001//National Natural Science Foundation of China/International ; 81572038//National Natural Science Foundation of China/International ; }, mesh = {Animals ; Candidiasis/drug therapy/*immunology ; Fecal Microbiota Transplantation/methods ; Humans ; Interleukin-17/*pharmacology/therapeutic use ; Mice ; Mice, Inbred C57BL ; Microbiota/drug effects/*physiology ; }, abstract = {BACKGROUND: The intestinal microbiota plays a crucial role in human health, which could affect host immunity and the susceptibility to infectious diseases. However, the role of intestinal microbiota in the immunopathology of invasive candidiasis remains unknown.<br><br>METHODS: In this work, an antibiotic cocktail was used to eliminate the intestinal microbiota of conventional-housed (CNV) C57/BL6 mice, and then both antibiotic-treated (ABX) mice and CNV mice were intravenously infected with Candida albicans to investigate their differential responses to infection. Furthermore, fecal microbiota transplantation (FMT) was applied to ABX mice in order to assess its effects on host immunity against invasive candidiasis after restoring the intestinal microbiota, and 16S ribosomal RNA gene sequencing was conducted on fecal samples from both uninfected ABX and CNV group of mice to analyze their microbiomes.<br><br>RESULTS: We found that ABX mice displayed significantly increased weight loss, mortality, and organ damage during invasive candidiasis when compared with CNV mice, which could be alleviated by FMT. In addition, the level of IL-17A in ABX mice was significantly lower than that in the CNV group during invasive candidiasis. Treatment with recombinant IL-17A could improve the survival of ABX mice during invasive candidiasis. Besides, the microbial diversity of ABX mice was significantly reduced, and the intestinal microbiota structure of ABX mice was significantly deviated from the CNV mice.<br><br>CONCLUSIONS: Our data revealed that intestinal microbiota plays a protective role in invasive candidiasis by enhancing IL-17A production in our model system.}, }
@article {pmid32457246, year = {2020}, author = {Abhyankar, MM and Ma, JZ and Scully, KW and Nafziger, AJ and Frisbee, AL and Saleh, MM and Madden, GR and Hays, AR and Poulter, M and Petri, WA}, title = {Immune Profiling To Predict Outcome of Clostridioides difficile Infection.}, journal = {mBio}, volume = {11}, number = {3}, pages = {}, pmid = {32457246}, issn = {2150-7511}, support = {R01 AI124214/AI/NIAID NIH HHS/United States ; R01 AI152477/AI/NIAID NIH HHS/United States ; }, mesh = {Aged ; Biomarkers/blood ; Clostridioides difficile/pathogenicity ; Clostridium Infections/diagnosis/*immunology/*mortality ; Cross Infection/diagnosis/immunology/microbiology ; Cytokines/*blood/immunology ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Mortality ; Precision Medicine ; Proportional Hazards Models ; Recurrence ; Retrospective Studies ; Risk Factors ; }, abstract = {There is a pressing need for biomarker-based models to predict mortality from and recurrence of Clostridioides difficile infection (CDI). Risk stratification would enable targeted interventions such as fecal microbiota transplant, antitoxin antibodies, and colectomy for those at highest risk. Because severity of CDI is associated with the immune response, we immune profiled patients at the time of diagnosis. The levels of 17 cytokines in plasma were measured in 341 CDI inpatients. The primary outcome of interest was 90-day mortality. Increased tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand 5 (CCL-5), suppression of tumorigenicity 2 receptor (sST-2), IL-8, and IL-15 predicted mortality by univariate analysis. After adjusting for demographics and clinical characteristics, the mortality risk (as indicated by the hazard ratio [HR]) was higher for patients in the top 25th percentile for TNF-α (HR = 8.35, P = 0.005) and IL-8 (HR = 4.45, P = 0.01) and lower for CCL-5 (HR = 0.18, P ≤ 0.008). A logistic regression risk prediction model was developed and had an area under the receiver operating characteristic curve (AUC) of 0.91 for 90-day mortality and 0.77 for 90-day recurrence. While limited by being single site and retrospective, our work resulted in a model with a substantially greater predictive ability than white blood cell count. In conclusion, immune profiling demonstrated differences between patients in their response to CDI, offering the promise for precision medicine individualized treatment.IMPORTANCEClostridioides difficile infection is the most common health care-associated infection in the United States with more than 20% patients experiencing symptomatic recurrence. The complex nature of host-bacterium interactions makes it difficult to predict the course of the disease based solely on clinical parameters. In the present study, we built a robust prediction model using representative plasma biomarkers and clinical parameters for 90-day all-cause mortality. Risk prediction based on immune biomarkers and clinical variables may contribute to treatment selection for patients as well as provide insight into the role of immune system in C. difficile pathogenesis.}, }
@article {pmid32457083, year = {2020}, author = {Merrick, B and Robinson, E and Bunce, C and Allen, L and Bisnauthsing, K and Izundu, CC and Bell, J and Amos, G and Shankar-Hari, M and Goodman, A and Shawcross, DL and Goldenberg, SD}, title = {Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organisms (FERARO): a prospective, randomised placebo-controlled feasibility trial.}, journal = {BMJ open}, volume = {10}, number = {5}, pages = {e038847}, pmid = {32457083}, issn = {2044-6055}, support = {MC_UU_12023/22/MRC_/Medical Research Council/United Kingdom ; MR/N030125/1/MRC_/Medical Research Council/United Kingdom ; PB-PG-0418-20007/DH_/Department of Health/United Kingdom ; }, mesh = {*Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Anti-Bacterial Agents/therapeutic use ; Feasibility Studies ; Humans ; London ; *Microbiota ; Prospective Studies ; }, abstract = {INTRODUCTION: Antimicrobial resistance is rising, largely due to the indiscriminate use of antimicrobials. The human gut is the largest reservoir of antibiotic resistant bacteria (ARB). Individuals colonised with ARB have the potential to spread these organisms both in the community and hospital settings. Infections with ARB such as extended spectrum beta-lactamase producing enterobacteriales (ESBL-E) and carbapenemase producing enterobacteriales (CPE) are more difficult to treat and are associated with an increased morbidity and mortality. Presently, there is no effective decolonisation strategy for these ARB. Faecal microbiota transplant (FMT) has emerged as a potential strategy for decolonisation of ARB from the human gut, however there is significant uncertainty about the feasibility, effectiveness and safety of using this approach.<br><br>METHODS AND ANALYSIS: Prospective, randomised, patient-blinded, placebo-controlled feasibility trial of FMT to eradicate gastrointestinal carriage of ARB. Eighty patients with a recent history of invasive infection secondary to ESBL-E or CPE and persistent gastrointestinal carriage will be randomised 1:1 to receive encapsulated FMT or placebo. The primary outcome measure is consent rate (as a proportion of patients who fulfil inclusion/exclusion criteria); this will be used to determine if a substantive trial is feasible. Participants will be followed up at 1&#x2009;week, 1&#x2009;month, 3 months and 6 months and monitored for adverse events as well as gastrointestinal carriage rates of ARB after intervention.<br><br>ETHICS AND DISSEMINATION: Research ethics approval was obtained by London-City and East Research Ethics Committee (ref 20/LO/0117). Trial results will be published in a peer-reviewed journal and presented at international conferences.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN registration number 34&#x2009;467&#x2009;677 and EudraCT number 2019-001618-41.}, }
@article {pmid32454215, year = {2020}, author = {Giannoni, L and Morin, F and Robin, M and Peyneau, M and Schlageter, MH and Desmier, D and Pagliuca, S and Sutra Del Galy, A and Sicre de Fontbrune, F and Xhaard, A and Dhedin, N and Moins-Teisserenc, H and Peffault de Latour, R and Socié, G and Michonneau, D}, title = {Human-Derived α1-Antitrypsin is Still Efficacious in Heavily Pretreated Patients with Steroid-Resistant Gastrointestinal Graft-versus-Host Disease.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {26}, number = {9}, pages = {1620-1626}, doi = {10.1016/j.bbmt.2020.05.014}, pmid = {32454215}, issn = {1523-6536}, mesh = {*Graft vs Host Disease/drug therapy ; Humans ; *Intestinal Diseases ; Remission Induction ; Retrospective Studies ; Steroids ; }, abstract = {Almost one-half of patients developing graft-versus-host disease (GVHD) will not respond to standard first-line steroid treatment. Alpha-1 antitrypsin (AAT) is able to induce tolerance in preclinical models of GVHD. AAT alters the cytokine milieu, promotes a tolerogenic shift of dendritic cells, and skews effector T cells toward regulatory T cells. Gastrointestinal steroid-refractory (SR)-GVHD is a protein-losing enteropathy that might represent the optimal setting in which to use AAT. Here we analyze the outcomes of 16 patients treated with human-derived AAT in advanced-stage gut SR-GVHD, with two-thirds of the patients having failed at least 1 treatment for SR-GVHD. The overall response rate (ORR) was 44%, with a complete response (CR) rate of 27%. Gastrointestinal response was observed in 61% of patients. The median time to best response was 21 days (range, 6 to 26 days). At day 56 after AAT treatment, all CRs were maintained, and the ORR was 39%. The 1-year overall survival was 48% (95% confidence interval, 26% to 74%). Ancillary studies showed that AAT serum levels were in the normal range at the beginning of treatment, whereas fecal loss was elevated. AAT levels consistently rose after exogenous administration, but no correlation was found between serum levels and response. REG3α and IL-33 levels were associated with response while, in contrast to previous reports, regulatory T cells decreased during AAT treatment. This retrospective analysis supports a previous report of AAT as a promising agent in the management of gut SR-GVHD and should prompt its evaluation at an earlier stage.}, }
@article {pmid32453670, year = {2020}, author = {Kaźmierczak-Siedlecka, K and Daca, A and Fic, M and van de Wetering, T and Folwarski, M and Makarewicz, W}, title = {Therapeutic methods of gut microbiota modification in colorectal cancer management - fecal microbiota transplantation, prebiotics, probiotics, and synbiotics.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1518-1530}, pmid = {32453670}, issn = {1949-0984}, mesh = {Animals ; Colorectal Neoplasms/microbiology/*therapy ; Combined Modality Therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics/*administration &amp; dosage ; Probiotics/*administration &amp; dosage ; Synbiotics/*administration &amp; dosage ; }, abstract = {The link between gut microbiota and the development of colorectal cancer has been investigated. An imbalance in the gut microbiota promotes the progress of colorectal carcinogenesis via multiple mechanisms, including inflammation, activation of carcinogens, and tumorigenic pathways as well as damaging host DNA. Several therapeutic methods are available with which to alter the composition and the activity of gut microbiota, such as administration of prebiotics, probiotics, and synbiotics; these can confer various benefits for colorectal cancer patients. Nowadays, fecal microbiota transplantation is the most modern way of modulating the gut microbiota. Even though data regarding fecal microbiota transplantation in colorectal cancer patients are still rather limited, it has been approved as a clinical method of treatment-recurrent Clostridium difficile infection, which may also occur in these patients. The major benefits of fecal microbiota transplantation include modulation of immunotherapy efficacy, amelioration of bile acid metabolism, and restoration of intestinal microbial diversity. Nonetheless, more studies are needed to assess the long-term effects of fecal microbiota transplantation. In this review, the impact of gut microbiota on the efficiency of anti-cancer therapy and colorectal cancer patients' overall survival is also discussed.}, }
@article {pmid32448639, year = {2020}, author = {Castro Rocha, FA and Duarte-Monteiro, AM and Henrique da Mota, LM and Matias Dinelly Pinto, AC and Fonseca, JE}, title = {Microbes, helminths, and rheumatic diseases.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {34}, number = {4}, pages = {101528}, pmid = {32448639}, issn = {1532-1770}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; Helminthiasis ; Humans ; Microbiota ; *Probiotics/therapeutic use ; *Rheumatic Diseases/microbiology/therapy ; }, abstract = {There has been a progressive interest on modifications of the human defense system following insults occurring in the interface between our body and the external environment, as they may provoke or worsen disease states. Studies suggest that billions of germs, which compose the gut microbiota influence one's innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. The microbiota of the skin, respiratory, and urinary tracts may also be relevant in rheumatology. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. Therapeutic strategies to modify the microbiota, including probiotics and fecal microbiota transplantation, have been received with skepticism, which, in turn, has drawn attention back to previously developed interventions such as antibiotics. Helminths adapted to humans over the evolution process, but their role in disease modulation, particularly immune-mediated diseases, remains to be understood. The present review focuses on data concerning modifications of the immune system induced by interactions with microbes and pluricellular organisms, namely helminths, and their impact on rheumatic diseases. Practical aspects, including specific microbiota-targeted therapies, are also discussed.}, }
@article {pmid32445528, year = {2020}, author = {Ostojic, SM}, title = {Letter: balancing gut hydrogen as a proxy for bacteriotherapy benefits in irritable bowel syndrome.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {51}, number = {12}, pages = {1451-1452}, doi = {10.1111/apt.15782}, pmid = {32445528}, issn = {1365-2036}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Hydrogen ; *Irritable Bowel Syndrome ; }, }
@article {pmid32445506, year = {2020}, author = {Sturiale, A and Fabiani, B and Celedon Porzio, F and Aglietti, R and Menconi, C and Naldini, G}, title = {Micro-fragmented autologous adipose tissue injection to treat anal incontinence - a video vignette.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {22}, number = {11}, pages = {1767-1768}, doi = {10.1111/codi.15155}, pmid = {32445506}, issn = {1463-1318}, mesh = {Adipose Tissue ; *Fecal Incontinence/etiology/therapy ; Humans ; Injections ; Transplantation, Autologous ; }, }
@article {pmid32444090, year = {2020}, author = {Jourde-Chiche, N and Burtey, S}, title = {Accumulation of protein-bound uremic toxins: the kidney remains the leading culprit in the gut-liver-kidney axis.}, journal = {Kidney international}, volume = {97}, number = {6}, pages = {1102-1104}, doi = {10.1016/j.kint.2020.02.026}, pmid = {32444090}, issn = {1523-1755}, mesh = {Humans ; Kidney ; Liver ; *Renal Insufficiency, Chronic/therapy ; *Toxins, Biological ; *Uremia ; }, abstract = {Protein-bound uremic toxins (PBUTs) accumulate in chronic kidney disease (CKD) and are poorly removed by dialysis. Gryp et al. demonstrated that fecal bacteria from patients with CKD do not produce more PBUTs than do those from healthy controls and that the accumulation of PBUTs, as CKD progresses, is mainly due to their reduced renal elimination by glomerular filtration and tubular secretion. This work underlines the importance of studying the metabolism of PBUTs along the diet-gut-liver-kidney axis.}, }
@article {pmid32443576, year = {2020}, author = {Kløve, S and Genger, C and Mousavi, S and Weschka, D and Bereswill, S and Heimesaat, MM}, title = {Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral Campylobacter coli Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota.}, journal = {Pathogens (Basel, Switzerland)}, volume = {9}, number = {5}, pages = {}, pmid = {32443576}, issn = {2076-0817}, support = {ZIM; ZF4117904 AJ8//Bundesministerium f&#xfc;r Forschung und Technologie/ ; Zoonoses research consortium PAC-Campylobacter, IP7/ 01KI1725D//Bundesministerium f&#xfc;r Bildung, Wissenschaft und Forschung/ ; }, abstract = {Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate C. coli-host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10[-/-] mice and IL10[-/-] controls to fecal microbiota transplantation derived from human donors by gavage, before peroral C. coli challenge. Until day 21 post-infection, C. coli could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10[-/-] mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10[-/-] counterparts. Furthermore, C. coli infected IL10[-/-], as opposed to TLR4-deficient IL10[-/-], mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon C. coli infection, which needs to be further addressed in more detail.}, }
@article {pmid32443032, year = {2020}, author = {Tessier, MEM and Cavallo, L and Yeh, J and Harpavat, S and Hoffman, KL and Petrosino, JF and Shneider, BL}, title = {The Fecal Microbiome in Infants With Biliary Atresia Associates With Bile Flow After Kasai Portoenterostomy.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {70}, number = {6}, pages = {789-795}, doi = {10.1097/MPG.0000000000002686}, pmid = {32443032}, issn = {1536-4801}, mesh = {Bile ; *Biliary Atresia/surgery ; Humans ; Infant ; *Liver Transplantation ; *Microbiota ; Portoenterostomy, Hepatic ; }, abstract = {BACKGROUND: Biliary atresia's (BA) response to surgical Kasai portoenterostomy (KP) is uneven and dependent upon bile flow; 50% of infants require a liver transplant by 24 months. We hypothesized that the microbiome may identify and associate with outcomes in BA.<br><br>METHODS: Stool samples were collected from infants with cholestasis (n&#x200a;=&#x200a;15), 8 of which with BA were followed longitudinally.16S sequencing was performed on all samples (n&#x200a;=&#x200a;45). Whole Genome Sequencing (WGS) was performed on BA pre-KP samples (n&#x200a;=&#x200a;8). Infants with BA, other forms of cholestasis, BA infants with very good bile flow (VGBF) and not (nVGBF) (VGBF dichotomized by TSBA <40&#x200a;&#x3bc;mol/L by 6 months) were compared.<br><br>RESULTS: Of the 8 infants with BA, 4 infants had VGBF. Microbial richness was inversely proportional to degree of cholestasis (P&#x200a;=&#x200a;0.046). Increased Bifidobacterium abundance associated with VGBF (P&#x200a;=&#x200a;0.03) and decreased cholestasis (P&#x200a;<&#x200a;0.01) at 1 month post-KP. Pre-KP, community structure differed in infants with BA versus other cholestasis. Interestingly, infants who subsequently achieved VGBF had increased diversity (P&#x200a;=&#x200a;0.03) and different community structure at the pre-KP time point. WGS corroborated Bifidobacterium's pre-KP importance.<br><br>CONCLUSIONS: The microbiome differs between infants with BA and other cholestasis. It additionally differs between infants with BA who have good and poor bile flow, and thus outcomes, post-KP. These differences are seen even before KP. These data suggest that bile influences the development of the infant microbiome and that there may be possible influences of the pre- and post-KP microbiome on bile flow after KP. Further larger studies are needed to confirm these findings.}, }
@article {pmid32440730, year = {2020}, author = {Birkeland, E and Gharagozlian, S and Birkeland, KI and Valeur, J and Måge, I and Rud, I and Aas, AM}, title = {Prebiotic effect of inulin-type fructans on faecal microbiota and short-chain fatty acids in type 2 diabetes: a randomised controlled trial.}, journal = {European journal of nutrition}, volume = {59}, number = {7}, pages = {3325-3338}, pmid = {32440730}, issn = {1436-6215}, support = {R21 DA036660/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Aged ; Cross-Over Studies ; *Diabetes Mellitus, Type 2/metabolism/microbiology ; Fatty Acids, Volatile/*analysis ; Feces/*microbiology ; Female ; Fermentation/drug effects ; Gastrointestinal Microbiome/*drug effects ; Humans ; Inulin/*chemistry/*pharmacology ; Male ; Middle Aged ; *Prebiotics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {PURPOSE: Compared to a healthy population, the gut microbiota in type 2 diabetes presents with several unfavourable features that may impair glucose regulation. The aim of this study was to evaluate the prebiotic effect of inulin-type fructans on the faecal microbiota and short-chain fatty acids (SCFA) in patients with type 2 diabetes.<br><br>METHODS: The study was a placebo controlled crossover study, where 25 patients (15 men) aged 41-71&#xa0;years consumed 16&#xa0;g of inulin-type fructans (a mixture of oligofructose and inulin) and 16-g placebo (maltodextrin) for 6&#xa0;weeks in randomised order. A 4-week washout separated the 6&#xa0;weeks treatments. The faecal microbiota was analysed by high-throughput 16S rRNA amplicon sequencing and SCFA in faeces were analysed using vacuum distillation followed by gas chromatography.<br><br>RESULTS: Treatment with inulin-type fructans induced moderate changes in the faecal microbiota composition (1.5%, p&#x2009;=&#x2009;0.045). A bifidogenic effect was most prominent, with highest positive effect on operational taxonomic units (OTUs) of Bifidobacterium adolescentis, followed by OTUs of Bacteroides. Significantly higher faecal concentrations of total SCFA, acetic acid and propionic acid were detected after prebiotic consumption compared to placebo. The prebiotic fibre had no effects on the concentration of butyric acid or on the overall microbial diversity.<br><br>CONCLUSION: Six weeks supplementation with inulin-type fructans had a significant bifidogenic effect and induced increased concentrations of faecal SCFA, without changing faecal microbial diversity. Our findings suggest a moderate potential of inulin-type fructans to improve gut microbiota composition and to increase microbial fermentation in type 2 diabetes.<br><br>TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT02569684).}, }
@article {pmid32440192, year = {2020}, author = {Elsalem, L and Jum'ah, AA and Alfaqih, MA and Aloudat, O}, title = {The Bacterial Microbiota of Gastrointestinal Cancers: Role in Cancer Pathogenesis and Therapeutic Perspectives.}, journal = {Clinical and experimental gastroenterology}, volume = {13}, number = {}, pages = {151-185}, pmid = {32440192}, issn = {1178-7023}, abstract = {The microbiota has an essential role in the pathogenesis of many gastrointestinal diseases including cancer. This effect is mediated through different mechanisms such as damaging DNA, activation of oncogenic pathways, production of carcinogenic metabolites, stimulation of chronic inflammation, and inhibition of antitumor immunity. Recently, the concept of "pharmacomicrobiomics" has emerged as a new field concerned with exploring the interplay between drugs and microbes. Mounting evidence indicates that the microbiota and their metabolites have a major impact on the pharmacodynamics and therapeutic responses toward anticancer drugs including conventional chemotherapy and molecular-targeted therapeutics. In addition, microbiota appears as an attractive target for cancer prevention and treatment. In this review, we discuss the role of bacterial microbiota in the pathogenesis of different cancer types affecting the gastrointestinal tract system. We also scrutinize the evidence regarding the role of microbiota in anticancer drug responses. Further, we discuss the use of probiotics, fecal microbiota transplantation, and antibiotics, either alone or in combination with anticancer drugs for prevention and treatment of gastrointestinal tract cancers.}, }
@article {pmid32437393, year = {2020}, author = {Fretheim, H and Chung, BK and Didriksen, H and Bækkevold, ES and Midtvedt, &#xd8; and Brunborg, C and Holm, K and Valeur, J and Tennøe, AH and Garen, T and Midtvedt, T and Trøseid, M and Zarè, H and Lund, MB and Hov, JR and Lundin, KEA and Molberg, &#xd8; and Hoffmann-Vold, AM}, title = {Fecal microbiota transplantation in systemic sclerosis: A double-blind, placebo-controlled randomized pilot trial.}, journal = {PloS one}, volume = {15}, number = {5}, pages = {e0232739}, pmid = {32437393}, issn = {1932-6203}, mesh = {Bacteria ; Double-Blind Method ; Fatty Acids/metabolism ; Fecal Incontinence/etiology ; *Fecal Microbiota Transplantation/adverse effects ; Feces/chemistry ; Female ; Humans ; Immunoglobulin A/metabolism ; Immunoglobulin M/metabolism ; Leukocyte L1 Antigen Complex/metabolism ; Male ; Middle Aged ; Pilot Projects ; Placebos ; Scleroderma, Systemic/*microbiology/*therapy ; Treatment Outcome ; }, abstract = {OBJECTIVES: Systemic sclerosis (SSc) is an auto-immune, multi organ disease marked by severe gastrointestinal (GI) involvement and gut dysbiosis. Here, we aimed to determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in SSc.<br><br>METHODS: Ten patients with SSc were randomized to ACHIM (n = 5) or placebo (n = 5) in a double-blind, placebo-controlled 16-week pilot. All patients had mild to severe upper and lower GI symptoms including diarrhea, distention/bloating and/or fecal incontinence at baseline. Gastroduodenoscopy transfer of ACHIM or placebo was performed at weeks 0 and 2. Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16. Secondary endpoints included changes in relative abundance of total, immunoglobulin (Ig) A- and IgM-coated fecal bacteria measured by 16s rRNA sequencing.<br><br>RESULTS: ACHIM side effects were mild and transient. Two placebo controls experienced procedure-related serious adverse events; one developed laryngospasms at week 0 gastroduodenoscopy necessitating study exclusion whilst one encountered duodenal perforation during gastroduodenoscopy at the last study visit (week 16). Decreased bloating, diarrhea and/or fecal incontinence was observed in four of five patients in the FMT group (week 4 or/and 16) and in two of four in the placebo group (week 4 or 16). Relative abundance, richness and diversity of total and IgA-coated and IgM-coated bacteria fluctuated more after FMT, than after placebo.<br><br>CONCLUSIONS: FMT of commercially-available ACHIM is associated with gastroduodenoscopy complications but reduces lower GI symptoms by possibly altering the gut microbiota in patients with SSc.}, }
@article {pmid32434586, year = {2020}, author = {Xiao, HW and Cui, M and Li, Y and Dong, JL and Zhang, SQ and Zhu, CC and Jiang, M and Zhu, T and Wang, B and Wang, HC and Fan, SJ}, title = {Gut microbiota-derived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {69}, pmid = {32434586}, issn = {2049-2618}, support = {P30 CA196521/CA/NCI NIH HHS/United States ; R01 AT005076/AT/NCCIH NIH HHS/United States ; R01 GM063075/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; *Diazepam Binding Inhibitor/metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry ; Female ; *Gastrointestinal Microbiome/drug effects/radiation effects ; Gastrointestinal Tract/drug effects/microbiology ; Hematopoiesis/drug effects ; *Indoles/administration &amp; dosage/pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Pregnane X Receptor/metabolism ; RNA, Ribosomal, 16S/genetics ; *Radiation Injuries/therapy ; Signal Transduction/drug effects ; }, abstract = {BACKGROUND: We have proved fecal microbiota transplantation (FMT) is an efficacious remedy to mitigate acute radiation syndrome (ARS); however, the mechanisms remain incompletely characterized. Here, we aimed to tease apart the gut microbiota-produced metabolites, underpin the therapeutic effects of FMT to radiation injuries, and elucidate the underlying molecular mechanisms.<br><br>RESULTS: FMT elevated the level of microbial-derived indole 3-propionic acid (IPA) in fecal pellets from irradiated mice. IPA replenishment via oral route attenuated hematopoietic system and gastrointestinal (GI) tract injuries intertwined with radiation exposure without precipitating tumor growth in male and female mice. Specifically, IPA-treated mice represented a lower system inflammatory level, recuperative hematogenic organs, catabatic myelosuppression, improved GI function, and epithelial integrity following irradiation. 16S rRNA gene sequencing and subsequent analyses showed that irradiated mice harbored a disordered enteric bacterial pattern, which was preserved after IPA administration. Notably, iTRAQ analysis presented that IPA replenishment retained radiation-reprogrammed protein expression profile in the small intestine. Importantly, shRNA interference and hydrodynamic-based gene delivery assays further validated that pregnane X receptor (PXR)/acyl-CoA-binding protein (ACBP) signaling played pivotal roles in IPA-favored radioprotection in vitro and in vivo.<br><br>CONCLUSIONS: These evidences highlight that IPA is a key intestinal microbiota metabolite corroborating the therapeutic effects of FMT to radiation toxicity. Owing to the potential pitfalls of FMT, IPA might be employed as a safe and effective succedaneum to fight against accidental or iatrogenic ionizing ARS in clinical settings. Our findings also provide a novel insight into microbiome-based remedies toward radioactive diseases. Video abstract.}, }
@article {pmid32431894, year = {2020}, author = {Koo, H and McFarland, BC and Hakim, JA and Crossman, DK and Crowley, MR and Rodriguez, JM and Benveniste, EN and Morrow, CD}, title = {An individualized mosaic of maternal microbial strains is transmitted to the infant gut microbial community.}, journal = {Royal Society open science}, volume = {7}, number = {4}, pages = {192200}, pmid = {32431894}, issn = {2054-5703}, support = {P30 CA013148/CA/NCI NIH HHS/United States ; R01 CA194414/CA/NCI NIH HHS/United States ; R03 NS116559/NS/NINDS NIH HHS/United States ; }, abstract = {To understand the origins of the infant gut microbial community, we have used a published metagenomic dataset of the faecal microbiome of mothers and their related infants at early (4, 7 and 21 days) and late times (6-15 months) following birth. Using strain-tracking analysis, individual-specific patterns of microbial strain sharing were found between mothers and infants following vaginal birth. Overall, three mother-infant pairs showed only related strains, while 12 infants of mother-infant pairs contained a mosaic of maternal-related and unrelated microbes. Analysis of a second dataset from nine women taken at different times of pregnancy revealed individual-specific faecal microbial strain variation that occurred in seven women. To model transmission in the absence of environmental microbes, we analysed the microbial strain transmission to F1 progenies of human faecal transplanted gnotobiotic mice bred with gnotobiotic males. Strain-tracking analysis of five different dams and their F1 progeny revealed both related and unrelated microbial strains in the mother's faeces. The results of our analysis demonstrate that multiple strains of maternal microbes, some that are not abundant in the maternal faecal community, can be transmitted during birth to establish a diverse infant gut microbial community.}, }
@article {pmid32430495, year = {2020}, author = {Markey, KA and Schluter, J and Gomes, ALC and Littmann, ER and Pickard, AJ and Taylor, BP and Giardina, PA and Weber, D and Dai, A and Docampo, MD and Armijo, GK and Slingerland, AE and Slingerland, JB and Nichols, KB and Brereton, DG and Clurman, AG and Ramos, RJ and Rao, A and Bush, A and Bohannon, L and Covington, M and Lew, MV and Rizzieri, DA and Chao, N and Maloy, M and Cho, C and Politikos, I and Giralt, S and Taur, Y and Pamer, EG and Holler, E and Perales, MA and Ponce, DM and Devlin, SM and Xavier, J and Sung, AD and Peled, JU and Cross, JR and van den Brink, MRM}, title = {The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD.}, journal = {Blood}, volume = {136}, number = {1}, pages = {130-136}, pmid = {32430495}, issn = {1528-0020}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; R01 AI032135/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 CA203950/CA/NCI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Allografts ; Bacteria/isolation &amp; purification/metabolism ; Butyrates/*blood ; Case-Control Studies ; Chronic Disease ; Dysbiosis/etiology/microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Graft vs Host Disease/blood/etiology/*microbiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Metabolome ; Propionates/*blood ; Ribotyping ; }, abstract = {Studies of the relationship between the gastrointestinal microbiota and outcomes in allogeneic hematopoietic stem cell transplantation (allo-HCT) have thus far largely focused on early complications, predominantly infection and acute graft-versus-host disease (GVHD). We examined the potential relationship of the microbiome with chronic GVHD (cGVHD) by analyzing stool and plasma samples collected late after allo-HCT using a case-control study design. We found lower circulating concentrations of the microbe-derived short-chain fatty acids (SCFAs) propionate and butyrate in day 100 plasma samples from patients who developed cGVHD, compared with those who remained free of this complication, in the initial case-control cohort of transplant patients and in a further cross-sectional cohort from an independent transplant center. An additional cross-sectional patient cohort from a third transplant center was analyzed; however, serum (rather than plasma) was available, and the differences in SCFAs observed in the plasma samples were not recapitulated. In sum, our findings from the primary case-control cohort and 1 of 2 cross-sectional cohorts explored suggest that the gastrointestinal microbiome may exert immunomodulatory effects in allo-HCT patients at least in part due to control of systemic concentrations of microbe-derived SCFAs.}, }
@article {pmid32429359, year = {2020}, author = {Amoroso, C and Perillo, F and Strati, F and Fantini, MC and Caprioli, F and Facciotti, F}, title = {The Role of Gut Microbiota Biomodulators on Mucosal Immunity and Intestinal Inflammation.}, journal = {Cells}, volume = {9}, number = {5}, pages = {}, pmid = {32429359}, issn = {2073-4409}, mesh = {Animals ; Dysbiosis/complications/immunology/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Immunity, Mucosal ; Immunologic Factors/*metabolism ; Inflammation/*immunology/*microbiology ; Intestines/*immunology/*microbiology ; }, abstract = {Alterations of the gut microbiota may cause dysregulated mucosal immune responses leading to the onset of inflammatory bowel diseases (IBD) in genetically susceptible hosts. Restoring immune homeostasis through the normalization of the gut microbiota is now considered a valuable therapeutic approach to treat IBD patients. The customization of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics and faecal microbiota transplantation, is therefore considered to support current therapies in IBD management. In this review, we will discuss recent advancements in the understanding of host-microbe interactions in IBD and the basis to promote homeostatic immune responses through microbe-targeted therapies. By considering gut microbiota dysbiosis as a key feature for the establishment of chronic inflammatory events, in the near future it will be suitable to design new cost-effective, physiologic, and patient-oriented therapeutic strategies for the treatment of IBD that can be applied in a personalized manner.}, }
@article {pmid32425906, year = {2020}, author = {Sun, Z and Li, J and Dai, Y and Wang, W and Shi, R and Wang, Z and Ding, P and Lu, Q and Jiang, H and Pei, W and Zhao, X and Guo, Y and Liu, J and Tan, X and Mao, T}, title = {Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {731}, pmid = {32425906}, issn = {1664-302X}, abstract = {Ulcerative colitis is a gastrointestinal disorder intricately associated with intestinal dysbiosis, but effective treatments are currently limited. Indigo naturalis, a traditional Chinese medicine derived from indigo plants, has been widely used in the treatment of ulcerative colitis. However, the specific mechanisms have not yet been identified. Accordingly, in this study, we evaluated the effects and mechanisms of indigo naturalis on dextran sulfate sodium (DSS)-induced colitis in rats. Our results showed that indigo naturalis potently alleviated DSS-induced colitis in rats, and reversed DSS-induced intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing. The protective effects of indigo naturalis were gut microbiota dependent, as demonstrated by antibiotic treatments and fecal microbiota transplantation. Depletion of the gut microbiota through a combination of antibiotic treatments blocked the anti-inflammatory effect of indigo naturalis on the DSS-induced colitis, and the recipients of the gut microbiota from indigo naturalis-treated rats displayed a significantly attenuated intestinal inflammation, which was actively responsive to therapeutic interventions with indigo naturalis. Notably, supplement with indigo naturalis greatly increased the levels of feces butyrate, which was positively correlated with the relative abundances of Ruminococcus_1 and Butyricicoccus. We further showed that indigo naturalis-dependent attenuation of colitis was associated with elevated expression of short-chain fatty acid-associated receptors GPR41 and GPR43. Collectively, these results suggested that indigo naturalis alleviates DSS-induced colitis in rats through a mechanism of the microbiota-butyrate axis, particularly alterations in Ruminococcus_1 and Butyricicoccus abundances, and target-specific microbial species may have unique therapeutic promise for ulcerative colitis.}, }
@article {pmid32423602, year = {2020}, author = {Bermejo Boixareu, C and Tutor-Ureta, P and Ramos Martínez, A}, title = {[Updated review of Clostridium difficile infection in elderly].}, journal = {Revista espanola de geriatria y gerontologia}, volume = {55}, number = {4}, pages = {225-235}, doi = {10.1016/j.regg.2019.12.003}, pmid = {32423602}, issn = {1578-1747}, mesh = {Aged ; *Clostridium Infections/diagnosis/epidemiology/physiopathology/therapy ; Humans ; Risk Factors ; }, abstract = {Clostridium difficile infection is the most common cause of health care-associated diarrhoea, and its incidence increases with age. Clinical challenges, risk of resistance to treatment, risk of recurrence, and treatment responses are different in elderly. The aim of this review is to discuss the updated epidemiology, pathophysiology, diagnosis, and therapeutic management of C. difficile infection in elderly with the available data.}, }
@article {pmid32423189, year = {2020}, author = {Zhang, W and Zou, G and Li, B and Du, X and Sun, Z and Sun, Y and Jiang, X}, title = {Fecal Microbiota Transplantation (FMT) Alleviates Experimental Colitis in Mice by Gut Microbiota Regulation.}, journal = {Journal of microbiology and biotechnology}, volume = {30}, number = {8}, pages = {1132-1141}, pmid = {32423189}, issn = {1738-8872}, mesh = {Animals ; Colitis, Ulcerative/chemically induced/microbiology/pathology/*therapy ; Colon/microbiology/pathology ; Cytokines/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred BALB C ; NF-kappa B/metabolism ; Oxidative Stress ; Signal Transduction ; }, abstract = {Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be considerable. Studies on fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study aims to demonstrate the ameliorative role of FMT in an ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) and elucidate its relative mechanisms in a mouse model. It was shown that FMT intervention decreased disease activity index (DAI) levels and increased the body weight, colon weight and colon length of experimental animals. It also alleviated histopathological changes, reduced key cytokine expression and oxidative status in the colon. A down-regulated expression level of genes associated with NF-κB signaling pathway was also observed. The results of 16S rRNA gene sequencing showed that FMT intervention restored the gut microbiota to the pattern of the control group by increasing the relative abundance of Firmicutes and decreasing the abundances of Bacteroidetes and Proteobacteria. The relative abundances of the genera Lactobacillus, Butyricicoccus, Lachnoclostridium, Olsenella and Odoribacter were upregulated but Helicobacter, Bacteroides and Clostridium were reduced after FMT administration. Furthermore, FMT administration elevated the concentrations of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.}, }
@article {pmid32422097, year = {2020}, author = {Talley, NJ and Irani, M}, title = {In irritable bowel syndrome, fecal microbiota transplantation improved symptoms at 3 months.}, journal = {Annals of internal medicine}, volume = {172}, number = {10}, pages = {JC52}, doi = {10.7326/ACPJ202005190-052}, pmid = {32422097}, issn = {1539-3704}, mesh = {Double-Blind Method ; *Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome ; }, abstract = {El-Salhy M, Hatlebakk JG, Gilja OH, Bråthen Kristoffersen A, Hausken T. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut. 2020;69:859-67. 31852769.}, }
@article {pmid32421761, year = {2020}, author = {Bauer, CM and Zhang, X and Long, MD and Sandler, RS}, title = {Characteristics of Fecal Microbiota Transplantation Use in Inflammatory Bowel Disease Cohort.}, journal = {Crohn's &amp; colitis 360}, volume = {2}, number = {2}, pages = {otaa024}, pmid = {32421761}, issn = {2631-827X}, support = {P30 DK034987/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: There is a growing interest in the role of gut bacteria in a number of diseases and an emerging hypothesis that inflammatory bowel disease (IBD) is triggered by microbial dysbiosis in genetically susceptible individuals. Currently, fecal microbiota transplantation (FMT) is utilized for the treatment of Clostridium difficile colitis. Data on the efficacy of FMT for IBD are mixed, but patients are interested in its use for the treatment of IBD. We sought to describe the use of FMT (self or medical professional administered) in individuals with IBD using IBD Partners, an Internet-based cohort.<br><br>METHODS: Patients enrolled in the IBD Partners cohort were offered the opportunity to complete an optional survey on the use of FMT between January 2017 to September 2018 (n = 5430). A cross-sectional analysis was performed within patients who completed the survey and did not have a pouch or ostomy. Patients' demographic characteristics, disease activity and phenotype, mode of FMT delivery, and patient-reported efficacy were compared.<br><br>RESULTS: Among 3274 eligible patients, 51 (1.6%) responded that they had an FMT in the past. Of patients undergoing FMT, 22 patients had the FMT for C. difficile while 29 reported that the FMT was for another indication. Most patients receiving FMT for an indication other than C. difficile had ulcerative colitis/indeterminate colitis (25, 86.2%). Colonoscopy (68.2%) and nasogastric tube (18.2%) were the most common routes of administration for patients receiving FMT for C. difficile colitis. Self-administration (72.4%) and enemas (17.2%) were the most common routes of administration in patients receiving FMT for an alternate indication. Patients reporting FMT for an indication other than C. difficile were less likely to have a physician directing their FMT treatment (20.6%) as compared to patients receiving FMT for C. difficile (86.3%). Patient-reported efficacy was lower for FMT given for a non-C. difficile indication.<br><br>CONCLUSIONS: Patients undergoing FMT for an indication other than C. difficile infection were more likely to have ulcerative colitis, self-administer FMT, and were less likely to be receiving FMT under the guidance of a medical professional. FMT was not as effective for symptoms when given for a non-C. difficile indication. Patients should be counseled on potential harms and lack of proven benefit associated with FMT for IBD indications to try to discourage self-administered FMT without proper medical oversite.}, }
@article {pmid32419454, year = {2020}, author = {Liu, Y and Luo, L and Luo, Y and Zhang, J and Wang, X and Sun, K and Zeng, L}, title = {Prebiotic Properties of Green and Dark Tea Contribute to Protective Effects in Chemical-Induced Colitis in Mice: A Fecal Microbiota Transplantation Study.}, journal = {Journal of agricultural and food chemistry}, volume = {68}, number = {23}, pages = {6368-6380}, doi = {10.1021/acs.jafc.0c02336}, pmid = {32419454}, issn = {1520-5118}, mesh = {Animals ; Camellia sinensis/*chemistry ; Colitis/drug therapy/etiology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects ; Humans ; Mice ; Plant Extracts/*administration &amp; dosage ; Prebiotics/administration &amp; dosage ; Tea/chemistry ; }, abstract = {Green and dark tea extract (GTE/DTE) ameliorate chemical-induced colitis in mice; however, the role of gut microbiota in the anticolitis effects of green and dark tea in mice remains unclear. This study aims to explore the role of modulations in gut microbes mediated by green and dark tea in colitis mice by fecal microbiota transplantation (FMT). Our results indicated that GTE and DTE (5 mg/kg bodyweight/day for 4 weeks) exhibited prebiotic effects on the donor mice. Moreover, the FMT treatments (transferring the microbiota daily from the 1 g/kg bodyweight fecal sample to each recipient) indicated that, compared with the fecal microbiota from the normal diet-treated donor mice, the fecal microbiota from the GTE- and DTE-treated donor mice significantly ameliorate colitis-related symptoms (e.g., loss of bodyweight, colonic inflammation, loss of barrier integrity, and gut microbiota dysbiosis) and downregulated the TLR4/MyD88/NF-κB pathway. Collectively, GTE and DTE ameliorate chemical-induced colitis by modulating gut microbiota.}, }
@article {pmid32419280, year = {2020}, author = {Suzuki, TA and Martins, FM and Phifer-Rixey, M and Nachman, MW}, title = {The gut microbiota and Bergmann's rule in wild house mice.}, journal = {Molecular ecology}, volume = {29}, number = {12}, pages = {2300-2311}, pmid = {32419280}, issn = {1365-294X}, support = {R01 GM074245/GM/NIGMS NIH HHS/United States ; R01 GM127468/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Body Size ; Ecology ; *Gastrointestinal Microbiome ; Mice/*microbiology ; North America ; South America ; }, abstract = {The extent to which the gut microbiota may play a role in latitudinal clines of body mass variation (i.e., Bergmann's rule) remains largely unexplored. Here, we collected wild house mice from three latitudinal transects across North and South America and investigated the relationship between variation in the gut microbiota and host body mass by combining field observations and common garden experiments. First, we found that mice in the Americas follow Bergmann's rule, with increasing body mass at higher latitudes. Second, we found that overall differences in the gut microbiota were associated with variation in body mass controlling for the effects of latitude. Then, we identified specific microbial measurements that show repeated associations with body mass in both wild-caught and laboratory-reared mice. Finally, we found that mice from colder environments tend to produce greater amounts of bacteria-driven energy sources (i.e., short-chain fatty acids) without an increase in food consumption. Our findings provide motivation for future faecal transplant experiments directly testing the intriguing possibility that the gut microbiota may contribute to Bergmann's rule, a fundamental pattern in ecology.}, }
@article {pmid32419054, year = {2021}, author = {Okamoto, T and Hatakeyama, S and Imai, A and Yamamoto, H and Yoneyama, T and Mori, K and Yoneyama, T and Hashimoto, Y and Nakaji, S and Ohyama, C}, title = {Altered gut microbiome associated with overactive bladder and daily urinary urgency.}, journal = {World journal of urology}, volume = {39}, number = {3}, pages = {847-853}, pmid = {32419054}, issn = {1433-8726}, support = {18K16682//Japan Society for the Promotion of Science/ ; 18K16717//Japan Society for the Promotion of Science/ ; }, mesh = {Aged ; Cross-Sectional Studies ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Urinary Bladder, Overactive/*etiology ; Urination Disorders/*etiology ; }, abstract = {PURPOSE: To explore associations between the gut microbiome and overactive bladder (OAB) with daily urinary urgency among individuals reporting this diagnosis within a single community.<br><br>METHODS: This cross-sectional study surveyed 1113 individuals who participated in the Iwaki Health Promotion Project in Japan. OAB was defined as urinary urgency at least once per week and an Overactive Bladder Symptom Score (OABSS) of&#x2009;&#x2265;&#x2009;3. OAB with urinary urgency at least once a day was defined as daily urgency. The gut microbiomes were assessed by next-generation sequencing of 16S rRNA genes extracted from fecal samples. The participants were divided into two groups: OAB-daily urgency and non-OAB. Cases were selected for inclusion on the basis of 1:1 propensity score matching; we assigned 58 individuals to each group (23 men and 35 women) for our analysis.<br><br>RESULTS: Individuals reporting OAB with daily urinary urgency demonstrated a lower bacterial diversity between individuals (Bray-Curtis distance 0.48 vs. 0.53, P&#x2009;<&#x2009;0.001); the results cluster differently in the non-OAB groups. The relative abundance of genus Bifidobacterium was significantly lower among those reporting daily urgency (2.41% vs. 4.23%, P&#x2009;=&#x2009;0.014). By contrast, the relative abundance of genus Faecalibacterium (9.25% vs. 6.26%, P&#x2009;=&#x2009;0.006) was significantly higher in this group.<br><br>CONCLUSION: We observed significant differences in gut microbial contents and specific bacterial genera in association with OAB with daily urgency. Further study will be necessary to assess causal relationships between the gut microbiome and OAB.}, }
@article {pmid32418496, year = {2020}, author = {Sharma, RK and Oliveira, AC and Yang, T and Karas, MM and Li, J and Lobaton, GO and Aquino, VP and Robles-Vera, I and de Kloet, AD and Krause, EG and Bryant, AJ and Verma, A and Li, Q and Richards, EM and Raizada, MK}, title = {Gut Pathology and Its Rescue by ACE2 (Angiotensin-Converting Enzyme 2) in Hypoxia-Induced Pulmonary Hypertension.}, journal = {Hypertension (Dallas, Tex. : 1979)}, volume = {76}, number = {1}, pages = {206-216}, pmid = {32418496}, issn = {1524-4563}, support = {R01 HL102033/HL/NHLBI NIH HHS/United States ; R01 HL142776/HL/NHLBI NIH HHS/United States ; P30 AG028740/AG/NIA NIH HHS/United States ; R01 HL033610/HL/NHLBI NIH HHS/United States ; R01 HL132448/HL/NHLBI NIH HHS/United States ; R01 HL142887/HL/NHLBI NIH HHS/United States ; }, mesh = {Angiotensin-Converting Enzyme 2/genetics/*physiology ; Animals ; Dysbiosis/enzymology/*etiology/microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gene Knock-In Techniques ; Hemodynamics ; Hypertension, Pulmonary/enzymology/etiology/*microbiology/prevention &amp; control ; Hypertrophy, Right Ventricular/etiology/prevention &amp; control ; Hypoxia/*complications/microbiology ; Inflammation ; Lung/enzymology/physiopathology ; Mice ; Microglia/pathology ; Paraventricular Hypothalamic Nucleus/pathology ; Sympathetic Nervous System/physiopathology ; }, abstract = {Therapeutic advances for pulmonary hypertension (PH) have been incremental because of the focus on the pulmonary vasculature in PH pathology. Here, we evaluate the concept that PH is, rather, a systemic disorder involving interplay among multiorgan systems, including brain, gut, and lungs. Therefore, the objective of this study was to evaluate the hypothesis that PH is associated with a dysfunctional brain-gut-lung axis and that global overexpression of ACE2 (angiotensin-converting enzyme 2) rebalances this axis and protects against PH. ACE2 knockin and wild-type (WT; C57BL/6) mice were subjected to chronic hypoxia (10% FIO2) or room air for 4 weeks. Cardiopulmonary hemodynamics, histology, immunohistochemistry, and fecal 16S rRNA microbial gene analyses were evaluated. Hypoxia significantly increased right ventricular systolic pressure, sympathetic activity as well as the number and activation of microglia in the paraventricular nucleus of the hypothalamus in WT mice. This was associated with a significant increase in muscularis layer thickening and decreases in both villi length and goblet cells and altered gut microbiota. Global overexpression of ACE2 prevented changes in hypoxia-induced pulmonary and gut pathophysiology and established distinct microbial communities from WT hypoxia mice. Furthermore, WT mice subjected to fecal matter transfer from ACE2 knockin mice were resistant to hypoxia-induced PH compared with their controls receiving WT fecal matter transfer. These observations demonstrate that ACE2 ameliorates these hypoxia-induced pathologies and attenuates PH. The data implicate dysfunctional brain-gut-lung communication in PH and provide novel avenues for therapeutic interventions.}, }
@article {pmid32415349, year = {2020}, author = {Chen, H and Xu, C and Zhang, F and Liu, Y and Guo, Y and Yao, Q}, title = {The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats.}, journal = {Cancer chemotherapy and pharmacology}, volume = {85}, number = {6}, pages = {1049-1062}, pmid = {32415349}, issn = {1432-0843}, mesh = {Animals ; Antimetabolites, Antineoplastic/*adverse effects ; Body Weight ; *Energy Metabolism ; Fecal Microbiota Transplantation/*methods ; Fluorouracil/*adverse effects ; *Gastrointestinal Microbiome ; Male ; Malnutrition/chemically induced/metabolism/pathology/*prevention &amp; control ; Muscular Atrophy/chemically induced/metabolism/pathology/*therapy ; Rats ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: Malnutrition is a common clinical symptom in cancer patients after chemotherapy, which is characterized by muscle wasting and metabolic dysregulation. The regulation of muscle metabolism by gut microbiota has been studied recently. However, there is no direct convincing evidence proving that manipulating gut microbiota homeostasis could regulate muscle metabolic disorder caused by chemotherapy. Here, we investigate the potential role of gut microbiota in the regulation of the muscle metabolism in 5-fluorouracil (5-Fu)-induced malnutrition rat model.<br><br>METHODS: Male Sprague-Dawley rats were randomly divided into two groups (n&#x2009;=&#x2009;8/group): control group and 5-Fu group. In the 5-Fu group, rats received 5-Fu (40&#xa0;mg/kg/day) by intraperitoneal injection for 4 days, and all rats were raised for 8 days. Nutritional status, muscle function, muscle metabolites, and gut microbiota were assessed. Fecal microbiota transplantation (FMT) was applied to explore the potential regulation of gut microbiota on muscle metabolism.<br><br>RESULTS: 5-Fu-treated rats exhibited loss of body weight and food intake compared to control group. 5-Fu decreased the levels of total protein and albumin in serum, and significantly increased the levels of IL-6 and TNF-&#x3b1; in muscle tissue. Rats that received 5-Fu displayed concurrent reduction of muscle function and fiber size. Moreover, 5-Fu group showed a distinct profile of gut microbiota compared to control group, including the relative lower abundance of Firmicutes and a higher abundance of Proteobacteria and Verrucomicrobia. Fourteen differential muscle metabolites were identified between two groups, which were mainly related to glycolysis, amino acid metabolism, and TCA cycle pathway. Furthermore, fecal transplantation from healthy rats improved nutritional status and muscle function in 5-Fu-treated rats. Notably, FMT inhibited the inflammatory response in muscle, and reversed the changes of several differential muscle metabolites and energy metabolism in 5-Fu-treated rats.<br><br>CONCLUSIONS: Our study demonstrated that gut microbiota played an important role in the regulation of muscle metabolism and promoting muscle energy production in 5-Fu-induced malnutrition rats, suggesting the potential attenuation of chemotherapy-induced muscle wasting by manipulating gut microbiota homeostasis.}, }
@article {pmid32414814, year = {2021}, author = {Camilleri, M}, title = {FMT in IBS: a call for caution.}, journal = {Gut}, volume = {70}, number = {2}, pages = {431}, doi = {10.1136/gutjnl-2020-321529}, pmid = {32414814}, issn = {1468-3288}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid32411633, year = {2020}, author = {Pagano, C and Venturi, M and Benegiamo, G and Melada, E and Vergani, C}, title = {Mucopexy-Recto Anal Lifting (MuRAL) in managing obstructed defecation syndrome associated with prolapsed hemorrhoids and rectocele: preliminary results.}, journal = {Annals of surgical treatment and research}, volume = {98}, number = {5}, pages = {277-282}, pmid = {32411633}, issn = {2288-6575}, abstract = {PURPOSE: Treatment of rectocele associated with prolapsed hemorrhoids is a debated topic. Transanal stapling achieved good midterm results in patients with symptoms of obstructed defecation, nevertheless a number of severe complications have been reported. The aim of this study was to evaluate the safety and efficacy of a new endorectal manual technique in patients with obstructed defecation due to the combination of muco-hemorrhoidal prolapse and rectocele.<br><br>METHODS: Patients enrolled after preoperative obstructed defecation syndrome (ODS) score, defecography and anoscopy were submitted to the novel Mucopexy-Recto Anal Lifting (MuRAL) combined with a modified Block procedure, and followed up by independent observers with digital exploration 3 weeks postoperatively, and digital exploration plus anoscopy at 3, 6, and 12 months. Operative time, hospital stay, numerating rating scale (NRS), ODS, satisfaction scores, and recurrence rate were recorded.<br><br>RESULTS: Mean operative time was 35.7 minutes. Fifty-six patients completed 1-year follow-up: 7.1% had acute urinary retention, NRS score was < 3 from the third postoperative day, mean time of daily activity resumption was 12 days, none had persistent fecal urgency, 82% declared excellent/good satisfaction score, significant improvement of 6- and 12-month ODS score, no recurrence of rectocele, and 7.1% recurrence of prolapsed hemorrhoids were observed.<br><br>CONCLUSION: MuRAL associated with modified Block technique gave no severe complications and resulted in a safe and effective approach to symptomatic rectocele associated with muco-rectal prolapse. Further randomized studies, larger series, and longer follow-up are needed.}, }
@article {pmid32410561, year = {2020}, author = {Alvarez-Vieites, E and López-Santamarina, A and Miranda, JM and Del Carmen Mondragón, A and Lamas, A and Cardelle-Cobas, A and Nebot, C and Franco, CM and Cepeda, A}, title = {Influence of the Intestinal Microbiota on Diabetes Management.}, journal = {Current pharmaceutical biotechnology}, volume = {21}, number = {15}, pages = {1603-1615}, doi = {10.2174/1389201021666200514220950}, pmid = {32410561}, issn = {1873-4316}, mesh = {Animals ; Diabetes Mellitus/*drug therapy/immunology/metabolism/microbiology ; Energy Metabolism/drug effects ; Gastrointestinal Microbiome/*drug effects ; Humans ; Inflammation ; Intestinal Absorption/drug effects/immunology ; Intestinal Mucosa/drug effects/immunology/microbiology ; Permeability ; Prebiotics/*administration &amp; dosage ; Probiotics/*therapeutic use ; }, abstract = {In recent decades, there has been a very rapid increase in the prevalence of diabetes globally, with serious health and economic implications. Although today there are several therapeutic treatments for this disease, these do not address the causes of the disease and have serious side effects, so it is necessary to seek new treatments to replace or complement the existing ones. Among these complementary treatments, a strong link between the intestinal microbiota and diabetes has been demonstrated, which has focused attention on the use of biotherapy to regulate the function of the intestinal microbiota and, thus, treat diabetes. In this way, the main objective of this work is to provide a review of the latest scientific evidence on diabetes, gathering information about new trends in its management, and especially, the influence of the intestinal microbiota and microbiome on this pathology. It is possible to conclude that the relationship between the intestinal microbiota and diabetes is carried out through alterations in energy metabolism, the immune system, changes in intestinal permeability, and a state of low-intensity systemic inflammation. Although, currently, most of the experimental work, using probiotics for diabetes management, has been done on experimental animals, the results obtained are promising. Thus, the modification of the microbiota through biotherapy has shown to improve the symptoms and severity of diabetes through various mechanisms related to these alterations.}, }
@article {pmid32409948, year = {2021}, author = {Grinspan, A}, title = {FMT for Severe C. difficile Infection: If at First You Do No Harm, the Second Time's a Charm.}, journal = {Digestive diseases and sciences}, volume = {66}, number = {1}, pages = {5-6}, pmid = {32409948}, issn = {1573-2568}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation ; Humans ; Risk Factors ; }, }
@article {pmid32407705, year = {2020}, author = {Fritsch, J and Abreu, MT}, title = {Candida in IBD: Friend or Foe?.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {5}, pages = {689-691}, doi = {10.1016/j.chom.2020.04.018}, pmid = {32407705}, issn = {1934-6069}, mesh = {Candida ; *Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Humans ; Inflammation ; }, abstract = {In this issue of Cell Host &amp; Microbe, Leonardi et al. demonstrate ulcerative colitis patients with high Candida responded best to fecal microbial transplant (FMT). However, decreased Candida post-treatment was associated with improved disease-suggesting that Candida reductions are associated with less inflammation. Pre-FMT Candida levels may identify FMT responders.}, }
@article {pmid32406522, year = {2020}, author = {Smyk, W and Janik, MK and Portincasa, P and Milkiewicz, P and Lammert, F and Krawczyk, M}, title = {COVID-19: Focus on the lungs but do not forget the gastrointestinal tract.}, journal = {European journal of clinical investigation}, volume = {50}, number = {9}, pages = {e13276}, pmid = {32406522}, issn = {1365-2362}, mesh = {Angiotensin-Converting Enzyme 2 ; Biomarkers/blood ; COVID-19 ; Comorbidity ; Coronavirus Infections/*epidemiology/physiopathology ; Disease Transmission, Infectious/prevention &amp; control/*statistics &amp; numerical data ; Female ; Gastrointestinal Diseases/*epidemiology/physiopathology ; Humans ; Male ; Pandemics/*statistics &amp; numerical data ; Peptidyl-Dipeptidase A/*blood ; Pneumonia, Viral/*epidemiology/physiopathology ; Prognosis ; Respiratory Distress Syndrome/diagnostic imaging/*epidemiology ; Risk Assessment ; }, abstract = {The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared in the last weeks as global pandemic. Currently affecting more than 5 000 000 individuals worldwide, COVID-19 is most commonly associated with symptoms caused by the acute respiratory distress syndrome (ARDS). As the number of infected individuals increases, we are learning that not only lungs, but also other organs can be affected by the virus. The gastrointestinal symptoms, for example diarrhoea, vomiting, nausea or abdominal pain, are frequent in patients with COVID-19. Moreover, alimentary tract symptoms may precede the respiratory presentation of SARS-CoV-2 infection. This can lead to delayed diagnosis and inappropriate management of infected patients. In addition, SARS-CoV-2 nucleic acid can be detected in faeces of infected patients and rectal swabs are even reported to remain positive for a longer period of time than nasopharyngeal swabs. Here, we aim to provide an update on the gastrointestinal involvement of COVID-19 presenting the symptoms that can be encountered in infected patients. We address the role of angiotensin-converting enzyme 2 (ACE2), as a functional receptor for SARS-CoV-2, which also was found in the gastrointestinal tract. Finally, we briefly discuss faecal shedding of SARS-CoV-2 and its potential role in the pathogenesis of the disease.}, }
@article {pmid32406264, year = {2021}, author = {Pereira, FV and Melo, ACL and Silva, MB and de Melo, FM and Terra, FF and Castro, IA and Perandini, LA and Miyagi, MT and Sato, FT and Origassa, CST and Hiyane, MI and Donato, J and Wasinski, F and Araujo, RC and Festuccia, WTL and da Silva, JS and Camara, NOS}, title = {Interleukin-6 and the Gut Microbiota Influence Melanoma Progression in Obese Mice.}, journal = {Nutrition and cancer}, volume = {73}, number = {4}, pages = {642-651}, doi = {10.1080/01635581.2020.1764982}, pmid = {32406264}, issn = {1532-7914}, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Interleukin-6 ; Leptin ; *Melanoma ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; }, abstract = {There is a strong correlation between obesity and cancer. Here, we investigated the influence of IL-6 and gut microbiota of obese mice in melanoma development. We first evaluated B16F10 melanoma growth in preclinical models for obesity: mice deficient for leptin (ob/ob) or adiponectin (AdpKO) and in wild-type mice (WT, C57BL/6J) fed a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. The survival rates of ob/ob and HFD-fed mice were lower than those of their respective controls. AdpKO mice also died earlier than WT control mice. We then verified the involvement of IL-6 signaling in obese mice that were inoculated with melanoma cells. Both ob/ob and AdpKO mice had higher circulating IL-6 levels than wild-type mice. Melanoma tumor volumes in IL-6 KO mice fed an HFD were reduced compared to those of WT mice subjected to the same diet. Also evaluated the effect of microbiota in tumor development. Cohousing and fecal matter transfer experiments revealed that microbiota from ob/ob mice can stimulate tumor development in lean WT mice. Taken together, our data show that in some conditions IL-6 and the gut microbiota are key mediators that link obesity and melanoma.}, }
@article {pmid32405509, year = {2020}, author = {Wilcox, MH and McGovern, BH and Hecht, GA}, title = {The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection: Current Understanding and Gap Analysis.}, journal = {Open forum infectious diseases}, volume = {7}, number = {5}, pages = {ofaa114}, pmid = {32405509}, issn = {2328-8957}, abstract = {The leading risk factor for Clostridioides (Clostridium) difficile infection (CDI) is broad-spectrum antibiotics, which lead to low microbial diversity, or dysbiosis. Current therapeutic strategies for CDI are insufficient, as they do not address the key role of the microbiome in preventing C. difficile spore germination into toxin-producing vegetative bacteria, which leads to symptomatic disease. Fecal microbiota transplant (FMT) appears to reduce the risk of recurrent CDI through microbiome restoration. However, a wide range of efficacy rates have been reported, and few placebo-controlled trials have been conducted, limiting our understanding of FMT efficacy and safety. We discuss the current knowledge gaps driven by questions around the quality and consistency of clinical trial results, patient selection, diagnostic methodologies, use of suppressive antibiotic therapy, and methods for adverse event reporting. We provide specific recommendations for future trial designs of FMT to provide improved quality of the clinical evidence to better inform treatment guidelines.}, }
@article {pmid32403888, year = {2020}, author = {Fan, LD and Liu, YM and Cheng, ML}, title = {[Probiotics enhance the efficacy of fecal microbiota transplantation in severe acute liver injury].}, journal = {Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology}, volume = {28}, number = {4}, pages = {345-350}, doi = {10.3760/cma.j.cn501113-20190823-00315}, pmid = {32403888}, issn = {1007-3418}, support = {81570543//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Bacteria/classification ; Chemical and Drug Induced Liver Injury/*therapy ; *Fecal Microbiota Transplantation ; Feces ; Gastrointestinal Microbiome ; Liver ; Male ; Mice ; Mice, Inbred BALB C ; Probiotics/*therapeutic use ; RNA, Ribosomal, 16S ; Random Allocation ; }, abstract = {Objective: To observe the changes of gut flora in mice, and explore the outcome of fecal microbiota transplantation combined with probiotics in the intervention of severe acute liver injury. Methods: Forty male BALB/c mice were selected and randomly divided into blank control group (10 mice), model group (10 mice), ordinary fecal microbiota transplantation group (10 mice), and fecal microbiota + probiotics transplantation group (10 mice). An intraperitoneal injection of d-galactosamine (D-GalN 3.0g/kg) was given to every group except the blank control group to induce severe acute liver injury model. Simultaneously, ordinary fecal microbiota transplantation group and fecal microbiota + probiotics transplantation group and modeling group were given enema solutions (once a day). After 48 hours, fetched serum was taken to detect alanine transaminase, aspartate transaminase and total bilirubin, and liver tissue was taken for pathological detection. The colonic content was used to extract DNA for 16S V3-V4 high-throughput sequencing. The results of sequencing were analyzed by using bioinformatics analysis; including OTU cluster analysis, α diversity analysis, β diversity analysis, and linear discriminant analysis effect size (Lefse) to find the bacteria with different colonic content characteristics in different groups of mice. Differences in clinical biochemical indicators between groups were compared using t-test, and the differences between 16S V3-V4 region sequencing results were compared using Wilcoxon test. Results: Model group mice serum biochemical parameters were higher than the other three groups, and the difference was statistically significant (P < 0.05). HE staining of liver sections showed severe inflammatory changes under the microscope in the model group. Ordinary fecal microbiota transplantation group and fecal microbiota + probiotic microbiota transplantation group had low levels of inflammation than the model group. The analysis results of 16S rRNA high-throughput sequencing showed that there was no statistically significant difference in Shannon's index between the blank control and the other three groups. Observed Species difference was statistically significant, and the gut flora composition varied greatly. Species number in the mice gut flora was increased with fecal microbiota transplantation. The results of β - diversity analysis showed that the difference between the blank control group and the other three groups was greater than that between the disease groups. The difference in the structure of the gut flora of the diseased mice in the fecal microbiota + probiotic transplantation group was mostly butyrate-producing bacteria. Conclusion: Fecal microbiota + probiotics enhance the therapeutic effect of fecal microbiota transplantation, improve liver inflammation, and increase the number of butyrate-producing bacteria in the gut.}, }
@article {pmid32402927, year = {2020}, author = {Shan, B and Ai, Z and Zeng, S and Song, Y and Song, J and Zeng, Q and Liao, Z and Wang, T and Huang, C and Su, D}, title = {Gut microbiome-derived lactate promotes to anxiety-like behaviors through GPR81 receptor-mediated lipid metabolism pathway.}, journal = {Psychoneuroendocrinology}, volume = {117}, number = {}, pages = {104699}, doi = {10.1016/j.psyneuen.2020.104699}, pmid = {32402927}, issn = {1873-3360}, mesh = {Animals ; *Anxiety/metabolism/microbiology/physiopathology ; Behavior, Animal/*physiology ; Cognitive Dysfunction/*metabolism ; Disease Models, Animal ; Gastrointestinal Microbiome/*physiology ; Hippocampus/*metabolism ; Lactic Acid/*adverse effects ; Male ; Metabolome/*physiology ; RNA, Ribosomal, 16S ; Rats ; Receptors, G-Protein-Coupled/*metabolism ; Signal Transduction/*physiology ; *Stress, Psychological/metabolism/microbiology/physiopathology ; }, abstract = {Accumulating evidence suggests that chronic stress could perturb the composition of the gut microbiota and induce host anxiety- and depression-like behaviors. In particular, microorganism-derived products that can directly or indirectly signal to the nervous system. This study sought to investigate whether high levels of Lactobacillus and lactate in the gut of rats under chronic unpredictable stress (CUS) were the factors leading to anxiety behavior. We collected faeces and blood samples in a sterile laboratory bench to study the microbiome and plasma metabolome from adult male rats age and environment matched healthy individuals. We sequenced the V3 and V4 regions of the 16S rRNA gene from faeces samples. UPLC-MS metabolomics were used to examine plasma samples. Search for potential biomarkers by combining the different data types. Finally, we found a regulated signaling pathway through the relative expression of protein and mRNA. Both lactate feeding and fecal microbiota transplantation caused behavioral abnormalities such as psychomotor malaise, impaired learning and memory in the recipient animals. These rats also showed inhibition of the adenylate cyclase (AC)-protein kinase A (PKA) pathway of lipolysis after activation of G protein-coupled receptor 81 (GPR81) by lactate in the liver, as well as increased tumor necrosis factor α (TNF-α), compared with healthy controls. Furthermore, we showed that sphingosine-1-phosphate receptor 2 (S1PR2) protein expression in hippocampus was reduced in chronic unpredictable stress compared to control group and its expression negatively correlates with symptom severity. Our study suggest that the gut microbiome-derived lactate promotes to anxiety-like behaviors through GPR81 receptor-mediated lipid metabolism pathway.}, }
@article {pmid32402683, year = {2021}, author = {Ren, G and Zhang, J and Li, M and Tang, Z and Yang, Z and Cheng, G and Wang, J}, title = {Gut microbiota composition influences outcomes of skeletal muscle nutritional intervention via blended protein supplementation in posttransplant patients with hematological malignancies.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {40}, number = {1}, pages = {94-102}, doi = {10.1016/j.clnu.2020.04.030}, pmid = {32402683}, issn = {1532-1983}, mesh = {Adolescent ; Adult ; Algorithms ; Case-Control Studies ; *Dietary Supplements ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Leukemia/*microbiology/physiopathology/therapy ; Male ; Muscle, Skeletal/microbiology/physiopathology ; Muscular Atrophy/etiology/microbiology/*therapy ; Principal Component Analysis ; RNA, Ribosomal, 16S/analysis ; Soybean Proteins/administration &amp; dosage ; Treatment Outcome ; Whey Proteins/administration &amp; dosage ; Young Adult ; }, abstract = {BACKGROUND: Skeletal muscle atrophy is an important and independent predictor of survival after hematopoietic stem cell transplantation (HSCT). Our previous study found that soy-whey blended protein (SWP) can improve muscle mass in acute leukemia patients.<br><br>OBJECTIVE: We aimed to explore potential factors that influence muscle outcomes after nutritional intervention.<br><br>METHODS: In this case-control study, 13 patients who received HSCT and failed to improve muscle function within half a year were included. After two months of SWP intervention, the subjects were divided into two groups (MSI: muscle status improved; MNI: muscle status not improved). 16S rDNA sequencing, principal coordinate analysis (PCoA) and the PICRUSt algorithm were used to analyze the composition, structure and function of the intestinal microbiota between the groups. This study was registered in the Chinese Clinical Trial Registry (ChiCTR 1800017765).<br><br>RESULTS: SWP significantly improved muscle status (muscle area: from 330.4&#xa0;mm[2] to 384.8&#xa0;mm[2], p&#xa0;=&#xa0;0.02; muscle strength: from 19.2&#xa0;kg to 21.3&#xa0;kg, p&#xa0;=&#xa0;0.04). However, there were a small number of subjects whose muscle status was not effectively improved. After SWP intervention, the diversity (Shannon: from 1.7 to 3.8, p&#xa0;=&#xa0;0.01; Simpson: from 0.6 to 0.8, p&#xa0;=&#xa0;0.015) of the intestinal microbiota in the MSI group increased significantly, whereas that in the MNI group did not. Principal component analysis (PCA) revealed separate groupings of the microbiota of the Baseline-MSI and Endpoint-MSI time points in the MSI group. Opposite patterns of microbial abundance change were found between the MSI group (75% of changed genera were increased) and the MNI group (80% of changed genera were decreased). Three bacterial taxa (negative correlation: Streptococcus; positive correlations: Ruminococcus and Veillonella) were significantly related to muscle improvement outcomes. Both pentose phosphate (p&#xa0;=&#xa0;0.048) and amino acid biosynthesis (p&#xa0;=&#xa0;0.039), which are related to muscle metabolism, were found to be significantly changed in the MSI group through PICRUSt algorithm prediction.<br><br>CONCLUSIONS: Our results suggest that the intestinal microbiota plays important roles in the regulation of muscle metabolism.}, }
@article {pmid32402176, year = {2020}, author = {DeFilipp, Z and Bloom, PP and Hohmann, EL and , }, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant. Reply.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1961-1962}, doi = {10.1056/NEJMc2002496}, pmid = {32402176}, issn = {1533-4406}, mesh = {*Bacteremia ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid32402175, year = {2020}, author = {Bleibtreu, A and Kapel, N and Galperine, T and , }, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1961}, doi = {10.1056/NEJMc2002496}, pmid = {32402175}, issn = {1533-4406}, mesh = {*Bacteremia ; Escherichia coli ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid32402174, year = {2020}, author = {Chiu, CH and Chiu, CT}, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1960-1961}, doi = {10.1056/NEJMc2002496}, pmid = {32402174}, issn = {1533-4406}, mesh = {*Bacteremia ; Escherichia coli ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid32402173, year = {2020}, author = {Janket, SJ and Ackerson, LK and Diamandis, EP}, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1960}, doi = {10.1056/NEJMc2002496}, pmid = {32402173}, issn = {1533-4406}, mesh = {*Bacteremia ; Escherichia coli ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid32397913, year = {2020}, author = {Barresi, L and Tacelli, M and Crinò, SF and Attili, F and Petrone, MC and De Nucci, G and Carrara, S and Manfredi, G and Capurso, G and De Angelis, CG and Crocellà, L and Fantin, A and Dore, MF and Garribba, AT and Tarantino, I and De Pretis, N and Pagliari, D and Rossi, G and Manes, G and Preatoni, P and Barbuscio, I and Tuzzolino, F and Traina, M and Frulloni, L and Costamagna, G and Arcidiacono, PG and Buscarini, E and Pezzilli, R and , }, title = {Multicentric Italian survey on daily practice for autoimmune pancreatitis: Clinical data, diagnosis, treatment, and evolution toward pancreatic insufficiency.}, journal = {United European gastroenterology journal}, volume = {8}, number = {6}, pages = {705-715}, pmid = {32397913}, issn = {2050-6414}, mesh = {Aftercare/standards/statistics &amp; numerical data ; Autoimmune Pancreatitis/blood/diagnosis/*drug therapy/epidemiology ; Biopsy ; Endoscopy ; Feces/enzymology ; Female ; Follow-Up Studies ; Gastroenterology/methods/standards/*statistics &amp; numerical data ; Glucocorticoids/*therapeutic use ; Guideline Adherence/statistics &amp; numerical data ; Humans ; Immunosuppressive Agents/*therapeutic use ; Italy/epidemiology ; Male ; Middle Aged ; Pancreas/diagnostic imaging/enzymology/immunology/pathology ; Pancreatic Elastase/analysis ; Practice Patterns, Physicians'/standards/*statistics &amp; numerical data ; Recurrence ; Retrospective Studies ; Rituximab/therapeutic use ; Secondary Prevention/methods/standards/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Autoimmune pancreatitis (AIP) is a rare, and relatively new, form of chronic pancreatitis. The management of AIP can vary considerably among different centres in daily clinical practice.<br><br>OBJECTIVES: The aim of this study is to present a picture of epidemiological, clinical characteristics, outcomes, and the real-life practice in terms of management in several academic and non-academic centres in Italy.<br><br>METHODS: Data on the clinical presentation, diagnostic work-up, treatments, frequency of relapses, and long-term outcomes were retrospectively collected in a cohort of AIP patients diagnosed at 14 centres in Italy.<br><br>RESULTS: One hundred and six patients were classified as type 1 AIP, 48 as type 2 AIP, and 19 as not otherwise specified. Epidemiological, clinical, radiological, and serological characteristics, and relapses were similar to those previously reported for different types of AIP. Endoscopic cytohistology was available in 46.2% of cases, and diagnostic for AIP in only 35.2%. Steroid trial to aid diagnosis was administered in 43.3% cases, and effective in 93.3%. Steroid therapy was used in 70.5% of cases, and effective in 92.6% of patients. Maintenance therapy with low dose of steroid (MST) was prescribed in 25.4% of cases at a mean dose of 5 (&#xb1;1.4) mg/die, and median time of MST was 60 days. Immunosuppressive drugs were rarely used (10.9%), and rituximab in 1.7%. Faecal elastase-1 was evaluated in only 31.2% of patients, and was pathological in 59.2%.<br><br>CONCLUSIONS: In this cohort of AIP patients, diagnosis and classification for subtype was frequently possible, confirming the different characteristics of AIP1 and AIP2 previously reported. Nevertheless, we observed a low use of histology and steroid trial for a diagnosis of AIP. Steroid treatment was the most used therapy in our cohort. Immunosuppressants and rituximab were rarely used. The evaluation of exocrine pancreatic insufficiency is underemployed considering its high prevalence.}, }
@article {pmid32393794, year = {2020}, author = {Kim, SM and DeFazio, JR and Hyoju, SK and Sangani, K and Keskey, R and Krezalek, MA and Khodarev, NN and Sangwan, N and Christley, S and Harris, KG and Malik, A and Zaborin, A and Bouziat, R and Ranoa, DR and Wiegerinck, M and Ernest, JD and Shakhsheer, BA and Fleming, ID and Weichselbaum, RR and Antonopoulos, DA and Gilbert, JA and Barreiro, LB and Zaborina, O and Jabri, B and Alverdy, JC}, title = {Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {2354}, pmid = {32393794}, issn = {2041-1723}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 GM062344/GM/NIGMS NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; T32 GM007281/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Butyric Acid/metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry ; Gastrointestinal Microbiome ; Gastrointestinal Tract/pathology ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; *Immunity ; Interferon Regulatory Factor-3/metabolism ; Male ; Mice, Inbred C57BL ; Sepsis/*immunology/microbiology/*therapy ; Signal Transduction ; Transcription, Genetic ; }, abstract = {Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.}, }
@article {pmid32392712, year = {2020}, author = {Iruzubieta, P and Medina, JM and Fernández-López, R and Crespo, J and de la Cruz, F}, title = {A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression.}, journal = {Journal of clinical medicine}, volume = {9}, number = {5}, pages = {}, pmid = {32392712}, issn = {2077-0383}, support = {BFU2017-86378-P//Ministerio de Ciencia y Tecnolog&#xed;a/ ; Gilead Fellowship programme 2018//Gilead Sciences/ ; PI18/01304//Ministerio de Ciencia, Innovaci&#xf3;n y Universidades/ ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.}, }
@article {pmid32390701, year = {2020}, author = {Chen, HT and Huang, HL and Li, YQ and Xu, HM and Zhou, YJ}, title = {Therapeutic advances in non-alcoholic fatty liver disease: A microbiota-centered view.}, journal = {World journal of gastroenterology}, volume = {26}, number = {16}, pages = {1901-1911}, pmid = {32390701}, issn = {2219-2840}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Clinical Trials as Topic ; Combined Modality Therapy/methods ; Disease Models, Animal ; Dysbiosis/complications/immunology/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*immunology ; Humans ; Intestinal Mucosa/drug effects/immunology/metabolism/microbiology ; Non-alcoholic Fatty Liver Disease/immunology/metabolism/microbiology/*therapy ; Prebiotics/administration &amp; dosage ; Probiotics/*administration &amp; dosage ; Synbiotics/administration &amp; dosage ; Treatment Outcome ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disorder with steadily increasing incidence rates worldwide, especially in the West. There are no drugs available at present to treat NAFLD, and the primary therapeutic options include weight loss and the combination of healthy diet and exercise. Therefore, novel interventions are required that can target the underlying risk factors. Gut microbiota is an "invisible organ" of the human body and vital for normal metabolism and immuno-modulation. The number and diversity of microbes differ across the gastrointestinal tract from the mouth to the anus, and is most abundant in the intestine. Since dysregulated gut microbiota is an underlying pathological factor of NAFLD, it is a viable therapeutic target that can be modulated by antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and microbial metabolites. In this review, we summarize the most recent advances in gut microbiota-targeted therapies against NAFLD in clinical and experimental studies, and critically evaluate novel targets and strategies for treating NAFLD.}, }
@article {pmid32390344, year = {2020}, author = {Young, RR and Jenkins, K and Araujo-Perez, F and Seed, PC and Kelly, MS}, title = {Long-term stability of microbiome diversity and composition in fecal samples stored in eNAT medium.}, journal = {MicrobiologyOpen}, volume = {9}, number = {7}, pages = {e1046}, pmid = {32390344}, issn = {2045-8827}, support = {K23 AI135090/AI/NIAID NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics/isolation &amp; purification ; Child ; Child, Preschool ; Cryopreservation/*methods ; Culture Media/*chemistry ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Specimen Handling/*methods ; }, abstract = {Fecal samples collected for microbiome analyses are typically frozen to avoid postcollection changes in microbial composition. eNAT is a guanidine thiocyanate-based medium that stabilizes microbial DNA and allows safe specimen handling and shipping by inactivating microorganisms. We collected fecal samples (n = 50) from children undergoing hematopoietic stem cell transplantation. We divided samples into three aliquots: (a) stored in RNAlater and immediately transferred to -80°C; (b) stored in eNAT medium and immediately transferred to -80°C; and (c) stored in eNAT medium at ambient temperature (~20°C) for 30 days prior to transfer to -80°C. Mean (standard deviation) Shannon diversity and Chao1 indices in sample aliquots were 2.05 (0.62) and 23.8 (16.6), respectively. Comparing samples frozen immediately in RNAlater to samples frozen immediately in eNAT, there were no differences in Shannon diversity (p = .51), Chao1 richness (p = .66), and overall microbiome composition (p = .99). Comparing eNAT samples frozen immediately to samples stored at ambient temperature, we identified no differences in Shannon diversity (p = .65), Chao1 richness (p = .87), and overall microbiome composition (p = .99). Storage of fecal samples in eNAT at ambient temperature for 30 days did not alter microbiome richness, diversity, or composition. eNAT may be a useful medium for fecal microbiome studies, particularly when cold chain storage is unavailable.}, }
@article {pmid32388604, year = {2020}, author = {Tang, LL and Feng, WZ and Cheng, JJ and Gong, YN}, title = {Clinical remission of ulcerative colitis after different modes of faecal microbiota transplantation: a meta-analysis.}, journal = {International journal of colorectal disease}, volume = {35}, number = {6}, pages = {1025-1034}, doi = {10.1007/s00384-020-03599-7}, pmid = {32388604}, issn = {1432-1262}, mesh = {Colitis, Ulcerative/*therapy ; Donor Selection ; Fecal Microbiota Transplantation/adverse effects/*methods ; Freezing ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic, recurrent and destructive disease of the gastrointestinal tract. Faecal microbiota transplantation (FMT) is a therapeutic measure in which faecal microbiota from healthy people is transplanted into patients.<br><br>AIM: To systematically evaluate the safety and effectiveness of treating UC with different modes of FMT.<br><br>METHODS: Seven databases were searched by two independent researchers and studies related to randomized controlled trials were included in the analysis.<br><br>RESULTS: Seven studies on UC involving 431 patients were included in the analysis. The results showed that FMT had better efficacy than placebo (OR&#x2009;=&#x2009;2.29, 95% CI 1.48-3.53, P&#x2009;=&#x2009;0.0002). Subgroup analyses of influencing factors showed that frozen faeces from multiple donors delivered via the lower gastrointestinal tract had a better curative effect than placebo (OR&#x2009;=&#x2009;2.76, 95% CI 1.59-4.79, P&#x2009;=&#x2009;0.0003; OR&#x2009;=&#x2009;2.93, 95% CI 1.67-5.71, P&#x2009;=&#x2009;0.0002; and OR&#x2009;=&#x2009;2.70, 95% CI 1.67-4.37, P&#x2009;<&#x2009;0.0001); the difference in efficacy between mixed faeces from a single donor transplanted through the upper gastrointestinal tract and placebo was not significant(P&#x2009;=&#x2009;0.05, P&#x2009;=&#x2009;0.09 and P&#x2009;=&#x2009;0.98). The analysis of side effects showed no significant difference between FMT and placebo (P&#x2009;=&#x2009;0.43).<br><br>CONCLUSIONS: It may be safe and effective to transplant frozen faeces from multiple donors through the lower gastrointestinal tract to treat UC.}, }
@article {pmid32388250, year = {2020}, author = {Wang, P and Wang, J and Li, D and Ke, W and Chen, F and Hu, X}, title = {Targeting the gut microbiota with resveratrol: a demonstration of novel evidence for the management of hepatic steatosis.}, journal = {The Journal of nutritional biochemistry}, volume = {81}, number = {}, pages = {108363}, doi = {10.1016/j.jnutbio.2020.108363}, pmid = {32388250}, issn = {1873-4847}, mesh = {Animals ; Antioxidants/administration &amp; dosage/pharmacology ; Bacteroides/drug effects ; Body Weight/drug effects ; Clostridiales/drug effects ; Diet, High-Fat ; Fatty Liver/metabolism ; Firmicutes/drug effects ; Gastrointestinal Microbiome/*drug effects ; Inflammation/metabolism ; Insulin Resistance ; Intestinal Mucosa/metabolism ; Lipid Metabolism/drug effects ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/*drug therapy/metabolism ; Obesity/metabolism ; Resveratrol/administration &amp; dosage/*pharmacology ; }, abstract = {Resveratrol is a natural polyphenol that has been reported to reduce the risk of obesity and nonalcoholic fatty liver disease (NAFLD). Recent evidence has demonstrated that the gut microbiota plays an important role in the protection against NAFLD and other metabolic diseases. The present study aimed to investigate the relationship between the gut microbiota and the beneficial effects of resveratrol on the amelioration of NAFLD in mice. We observed marked decreases in body weight and liver steatosis and improved insulin resistance in high-fat diet (HFD)-fed mice treated with resveratrol. Furthermore, we found that resveratrol treatment alleviated NAFLD in HFD-fed mice by improving the intestinal microenvironment, including gut barrier function and gut microbiota composition. On the one hand, resveratrol improved gut intestinal barrier integrity through the repair of intestinal mucosal morphology and increased the expression of physical barrier- and physiochemical barrier-related factors in HFD-fed mice. On the other hand, in HFD-fed mice, resveratrol supplementation modulated the gut bacterial composition. The resveratrol-induced gut microbiota was characterized by a decreased abundance of harmful bacteria, including Desulfovibrio, Lachnospiraceae_NK4A316_group and Alistipes, as well as an increased abundance of short-chain fatty acid (SCFA)-producing bacteria, such as Allobaculum, Bacteroides and Blautia. Moreover, transplantation of the HFDR-microbiota into HFD-fed mice sufficiently decreased body weight, liver steatosis and low-grade inflammation and improved hepatic lipid metabolism. Collectively, resveratrol would provide a potentially dietary intervention strategy against NAFLD through modulating the intestinal microenvironment.}, }
@article {pmid32385726, year = {2020}, author = {Loconte, I and Principi, M and Ingravallo, G and Castellaneta, N and Ierardi, E and Di Leo, A}, title = {Recurrent Overt Gastrointestinal Bleeding from Ulcerated Gastric Elastofibroma: Unprecedented Presentation of a Rare Condition.}, journal = {Journal of gastrointestinal cancer}, volume = {51}, number = {3}, pages = {1074-1076}, doi = {10.1007/s12029-020-00412-0}, pmid = {32385726}, issn = {1941-6636}, mesh = {Aged ; Anemia/*etiology/surgery ; Endosonography ; Female ; Fibroma/complications/*diagnosis/pathology/surgery ; Gastrectomy ; Gastric Mucosa/blood supply/diagnostic imaging/pathology ; Gastroscopy ; Humans ; Melena/*etiology/surgery ; Recurrence ; Stomach Neoplasms/complications/*diagnosis/pathology/surgery ; Stomach Ulcer/*etiology/surgery ; Treatment Outcome ; }, }
@article {pmid32376136, year = {2020}, author = {Derosa, L and Routy, B and Fidelle, M and Iebba, V and Alla, L and Pasolli, E and Segata, N and Desnoyer, A and Pietrantonio, F and Ferrere, G and Fahrner, JE and Le Chatellier, E and Pons, N and Galleron, N and Roume, H and Duong, CPM and Mondragón, L and Iribarren, K and Bonvalet, M and Terrisse, S and Rauber, C and Goubet, AG and Daillère, R and Lemaitre, F and Reni, A and Casu, B and Alou, MT and Alves Costa Silva, C and Raoult, D and Fizazi, K and Escudier, B and Kroemer, G and Albiges, L and Zitvogel, L}, title = {Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients.}, journal = {European urology}, volume = {78}, number = {2}, pages = {195-206}, doi = {10.1016/j.eururo.2020.04.044}, pmid = {32376136}, issn = {1873-7560}, mesh = {Animals ; Carcinoma, Renal Cell/*drug therapy/*microbiology ; *Drug Resistance, Neoplasm ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Kidney Neoplasms/*drug therapy/*microbiology ; Mice ; Nivolumab/*therapeutic use ; Predictive Value of Tests ; Prospective Studies ; }, abstract = {BACKGROUND: The development of immune checkpoint blockade (ICB) has revolutionized the clinical outcome of renal cell carcinoma (RCC). Nevertheless, improvement of durability and prediction of responses remain unmet medical needs. While it has been recognized that antibiotics (ATBs) decrease the clinical activity of ICB across various malignancies, little is known about the direct impact of distinct intestinal nonpathogenic bacteria (commensals) on therapeutic outcomes of ICB in RCC.<br><br>OBJECTIVE: To evaluate the predictive value of stool bacteria composition for ICB efficacy in a cohort of advanced RCC patients.<br><br>We prospectively collected fecal samples from 69 advanced RCC patients treated with nivolumab and enrolled in the GETUG-AFU 26 NIVOREN microbiota translational substudy phase 2 trial (NCT03013335) at Gustave Roussy. We recorded patient characteristics including ATB use, prior systemic therapies, and response criteria. We analyzed 2994 samples of feces from healthy volunteers (HVs). In parallel, preclinical studies performed in RCC-bearing mice that received fecal transplant (FMT) from RCC patients resistant to ICB (NR-FMT) allowed us to draw a cause-effect relationship between gut bacteria composition and clinical outcomes for ICB. The influence of tyrosine kinase inhibitors (TKIs) taken before starting nivolumab on the microbiota composition has also been assessed.<br><br>Metagenomic data (MG) from whole genome sequencing (WGS) were analyzed by multivariate and pairwise comparisons/fold ratio to identify bacterial fingerprints related to ATB or prior TKI exposure and patients' therapeutic response (overall response and progression-free survival), and compared with the data from cancer-free donors.<br><br>RESULTS AND LIMITATIONS: Recent ATB use (n&#x202f;=&#x202f;11; 16%) reduced objective response rates (from 28% to 9%, p&#x202f;<&#x202f;0.03) and markedly affected the composition of the microbiota, facilitating the dominance of distinct species such as Clostridium hathewayi, which were also preferentially over-represented in stools from RCC patients compared with HVs. Importantly, TKIs taken prior to nivolumab had implications in shifting the microbiota composition. To establish a cause-effect relationship between gut bacteria composition and ICB efficacy, NR-FMT mice were successfully compensated with either FMT from responding RCC patients or beneficial commensals identified by WGS-MG (Akkermansia muciniphila and Bacteroides salyersiae).<br><br>CONCLUSIONS: The composition of the microbiota is influenced by TKIs and ATBs, and impacts the success of immunotherapy. Future studies will help sharpen the role of these specific bacteria and their potential as new biomarkers.<br><br>PATIENT SUMMARY: We used quantitative shotgun DNA sequencing of fecal microbes as well as preclinical models of fecal or bacterial transfer to study the association between stool composition and (pre)clinical outcome to immune checkpoint blockade. Novel insights into the pathophysiological relevance of intestinal dysbiosis in the prognosis of kidney cancer may lead to innovative therapeutic solutions, such as supplementation with probiotics to prevent primary resistance to therapy.}, }
@article {pmid32375675, year = {2020}, author = {Zhang, T and Long, C and Cui, B and Buch, H and Wen, Q and Li, Q and Ding, X and Ji, G and Zhang, F}, title = {Colonic transendoscopic tube-delivered enteral therapy (with video): a prospective study.}, journal = {BMC gastroenterology}, volume = {20}, number = {1}, pages = {135}, pmid = {32375675}, issn = {1471-230X}, support = {81670495//National Natural Science Foundation of China/ ; 81600417//National Natural Science Foundation of China/ ; -//Jiangsu Province Creation Team and Leading Talents project/ ; LGY2017080//Top-notch Talent Research Projects/ ; -//public donated Intestine Initiative Foundation/ ; }, mesh = {Adult ; Colitis, Ulcerative/therapy ; Colonoscopy/*methods ; Constipation/therapy ; Feasibility Studies ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Agents/*administration &amp; dosage ; Humans ; *Infusion Pumps, Implantable ; Intestinal Diseases/*therapy ; Intubation, Gastrointestinal/*methods ; Male ; Middle Aged ; Patient Satisfaction ; Prospective Studies ; Surgical Instruments/statistics &amp; numerical data ; Treatment Outcome ; }, abstract = {BACKGROUND: Colonic transendoscopic enteral tubing (TET) refers to colonic transendoscopic tube-delivered enteral therapy. Colonic TET has been successfully used for frequent colonic administration of drugs or multiple fecal microbiota transplantations (FMTs). This prospective observational study aimed to evaluate possible factors affecting methodology, feasibility and safety of colonic TET.<br><br>METHODS: Patients who underwent colonic TET at our center from October 2014 to November 2018 were included. The feasibility, efficacy, and safety of TET were evaluated.<br><br>RESULTS: In total, 224 patients were analyzed. The success rate of TET was 100%. The median retention time of TET tube within the colonic lumen was 8.5 (IQR 7-11) days in 158 patients with tube falling out spontaneously, and the maximum retention time was up to 28&#x2009;days. These patients were divided into the short-retention group (&#x2264; 8.5&#x2009;days) and the long-retention group (>&#x2009;8.5&#x2009;days). Univariate and multivariate analysis demonstrated that the type of endoscopic clip (p&#x2009;=&#x2009;0.001) was an independent factor for the retention time. The larger clips as well as a greater number of clips significantly affected the retention time (p&#x2009;=&#x2009;0.013). No severe adverse event was observed during and after TET.<br><br>CONCLUSIONS: Colonic TET is a feasible, practical, and safe colon-targeted drug delivery technique with a high degree of patients' satisfaction. Two to four large endoscopic clips are recommended to maintain stability of the TET tube within the colon for over 7&#x2009;days.}, }
@article {pmid32373209, year = {2020}, author = {Liu, YJ and Tang, B and Wang, FC and Tang, L and Lei, YY and Luo, Y and Huang, SJ and Yang, M and Wu, LY and Wang, W and Liu, S and Yang, SM and Zhao, XY}, title = {Parthenolide ameliorates colon inflammation through regulating Treg/Th17 balance in a gut microbiota-dependent manner.}, journal = {Theranostics}, volume = {10}, number = {12}, pages = {5225-5241}, pmid = {32373209}, issn = {1838-7640}, mesh = {Animals ; Colonoscopy ; Dextran Sulfate/toxicity ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Gastrointestinal Microbiome/drug effects ; Inflammation/*chemically induced/*drug therapy ; Inflammatory Bowel Diseases/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics/metabolism ; Sesquiterpenes/*therapeutic use ; T-Lymphocytes, Regulatory/drug effects/metabolism ; Th17 Cells/drug effects/metabolism ; }, abstract = {Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays an important pathogenic role. However, the current drugs for IBD treatment are far from optimal. Previous researches indicated that parthenolide (PTL) had not only anti-cancer properties but also strong anti-inflammatory activities. Rationale: To investigate the protective effect of PTL on colon inflammation and demonstrate the underlying gut microbiota-dependent mechanism. Methods: Colon inflammation severity in mouse model was measured by body weight change, mortality, colon length, disease activity index (DAI) score, H&amp;E staining and colonoscopy evaluation. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Luminex cytokine microarray and Enzyme-linked immunosorbent assay (ELISA) were conducted to measure the colon cytokines profile. The frequency of immune cells in lamina propria (LP) and spleen were phenotyped by flow cytometry. Results: The PTL-treated mice showed significantly relieved colon inflammation, as evidenced by a reduction in body weight loss, survival rate, shortening of colon length, DAI score, histology score and colonoscopy score. Notably, when the gut microbiota was depleted using antibiotic cocktails, the protective effect of PTL on colon inflammation disappeared. PTL treatment downregulated the level of proinflammatory cytokines, including IL-1β, TNF-α, IL-6, and IL-17A and upregulated the immunosuppressive cytokine IL-10 in colon tissue. 16S rRNA sequencing indicated that PTL-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased SCFAs production in PTL-treated mice. Additionally, PTL administration selectively upregulated the frequency of colonic regulatory T (Treg) cells as well as downregulated the ratio of colonic T helper type 17 (Th17) cells, improving the Treg/Th17 balance to maintain intestinal homeostasis. Gut microbiota depletion and fecal microbiota transplantation (FMT) was performed to confirm this gut microbiota-dependent mechanism. Conclusions: PTL ameliorated colon inflammation in a gut microbiota-dependent manner. The underlying protective mechanism was associated with the improved Treg/Th17 balance in intestinal mucosa mediated through the increased microbiota-derived SCFAs production. Collectively, our results demonstrated the role of PTL as a potential gut microbiota modulator to prevent and treat IBD.}, }
@article {pmid32368882, year = {2020}, author = {Nakov, R and Segal, JP and Settanni, CR and Bibbò, S and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {Microbiome: what intensivists should know.}, journal = {Minerva anestesiologica}, volume = {86}, number = {7}, pages = {777-785}, doi = {10.23736/S0375-9393.20.14278-0}, pmid = {32368882}, issn = {1827-1596}, mesh = {Critical Illness ; Dysbiosis ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; *Probiotics ; }, abstract = {The standard conditions of critical illness (including sepsis, acute respiratory distress syndrome, and multiorgan failure) cause enormous global mortality and a growing economic burden. Increasing evidence suggests that critical illness may be associated with loss of commensal microbes and overgrowth of potentially pathogenic and inflammatory bacteria. This state could be associated with poor outcomes. Therefore, microbiota-targeted interventions are potentially attractive novel treatment options. Although the precise mechanisms of microbiome-directed treatments such as prebiotics, probiotics, and fecal microbiota transplantation remain to be determined, they can be utilized in the Intensive Care Unit (ICU) setting. The current review aims to offer intensivists an evidenced-based approach on what we currently know about the role of the microbiome in critical illness and how the microbiome could be targeted in the clinical practice to improve ICU-related outcomes.}, }
@article {pmid32365381, year = {2020}, author = {Jørgensen, SMD and Rubak, TMM and Damsgaard, EM and Dahlerup, JF and Hvas, CL}, title = {Faecal microbiota transplantation as a home therapy to frail older people.}, journal = {Age and ageing}, volume = {49}, number = {6}, pages = {1093-1096}, pmid = {32365381}, issn = {1468-2834}, mesh = {Aged ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation/adverse effects ; Frail Elderly ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Clostridioides (Clostridium) difficile infection (CDI) is a leading cause of antibiotics-associated diarrhoea. Faecal microbiota transplantation (FMT) is effective for recurrent CDI and may be provided as a home treatment to frail, older people.<br><br>METHODS: We present four consecutive patients with recurrent CDI, treated at home using nasojejunal tube-delivered or encapsulated donor faeces. The primary outcome was combined clinical resolution and a negative CD toxin test 8 weeks post-treatment.<br><br>RESULTS: All four patients had severe CDI and all improved clinically following one FMT. Sustained resolution following one FMT was observed in one patient. Two patients had recurrence and received a second FMT using capsules; both achieved resolution. One patient who had recurrence declined from further FMT due to fear of relapse and was established on long-term vancomycin. No adverse events related to FMT were observed.<br><br>CONCLUSION: Frail older people may benefit from FMT. Home treatment is a viable option and may be considered both for clinical cure and for palliation.}, }
@article {pmid32364071, year = {2020}, author = {Tarasiuk, A and Eibl, G}, title = {Nutritional Support and Probiotics as a Potential Treatment of IBD.}, journal = {Current drug targets}, volume = {21}, number = {14}, pages = {1417-1427}, doi = {10.2174/1389450121666200504075519}, pmid = {32364071}, issn = {1873-5592}, support = {POIR.04.04.00-00-420C/2017//Kosciuszko Foundation (The American Centre of Polish Culture, Foundation)/ ; 502-03/1-156-04/502-14-361-18//Medical University of Lodz/ ; }, mesh = {Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/etiology/microbiology/*therapy ; *Nutrition Therapy ; Probiotics/*therapeutic use ; }, abstract = {The pathogenesis of inflammatory bowel disease (IBD) remains unknown. However, there is growing evidence that the increase in the overall incidence of IBD relates to the improvement of sanitary and hygienic conditions of the society leading to lower exposure to both bacterial and parasitic infections. IBD is incurable and characterized by alternating periods of exacerbation and remission of symptoms. Therefore, the main goal of treatment strategies in IBD patients is the most effective maintenance of clinical and endoscopic remission, which does allow patients to function normally for a significant part of life. Taking into account the evidence from different areas, there is a strong rationale supporting the concept that bacteria are important in gut inflammation and that probiotic bacteria may modulate the host-microbe interaction in a way that is directly beneficial to IBD patients along with nutritional support. In this review, we focus on the potential role of gastrointestinal microbiota in the pathogenesis of IBD and the possible value of probiotics, prebiotics, and symbiotics as well as nutritional support in the treatment of IBD.}, }
@article {pmid32363202, year = {2020}, author = {Chaitman, J and Ziese, AL and Pilla, R and Minamoto, Y and Blake, AB and Guard, BC and Isaiah, A and Lidbury, JA and Steiner, JM and Unterer, S and Suchodolski, JS}, title = {Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole.}, journal = {Frontiers in veterinary science}, volume = {7}, number = {}, pages = {192}, pmid = {32363202}, issn = {2297-1769}, abstract = {The aim was to characterize differences in fecal consistency, and fecal microbiota and metabolome profiles in dogs with acute diarrhea (AD) treated with either fecal microbiota transplantation as enema (FMT; n = 11) or oral metronidazole (MET; n = 7) for 7 days. On days 0, 7, and 28 fecal samples were obtained. Fecal samples from healthy dogs (HC; n = 14) were used for comparison. Samples were analyzed by the previously validated qPCR based canine Dysbiosis Index (DI; increased values indicate microbiota dysbiosis) and 16S rRNA gene sequencing. The fecal metabolome was analyzed using a previously validated targeted canine assay for fecal unconjugated bile acids, and untargeted metabolomics. Fecal consistency improved significantly in dogs treated with FMT and MET by day 7 and day 28 (p < 0.01) compared to day 0. However, on day 28 fecal consistency was significantly better in FMT compared to MET (p = 0.040). At day 0, dogs with AD had an altered microbiota indicated by significantly increased DI, decreased alpha-diversity, and altered beta-diversity. In the FMT group, the DI decreased over time, while MET led to a significant increase in the dysbiosis index at day 7 and 28 compared to FMT. Sequencing data revealed that in FMT microbial diversity and beta-diversity was similar to HC at day 28, while in MET these parameters were still significantly different from HC. In dogs treated with FMT, a decrease in cholic acid and the percentage of primary bile acids was observed, whereas treatment with metronidazole led to an increase in cholic acid at day 7 and an increase in percentage of primary bile acids over time. Based on untargeted metabolomics, dogs with AD had an altered fecal metabolome compared to HC. Dogs treated with FMT clustered closer to HC at day 28, while dogs treated with MET did not. In this pilot study, dogs with AD had significant differences in fecal microbiota and metabolome profiles. Dogs treated with MET still had altered microbial and metabolic profiles at day 28 compared to dogs treated with FMT or healthy dogs.}, }
@article {pmid32359480, year = {2020}, author = {Frisbee, AL and Petri, WA}, title = {Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection.}, journal = {Trends in molecular medicine}, volume = {26}, number = {5}, pages = {496-507}, pmid = {32359480}, issn = {1471-499X}, support = {F31 AI136421/AI/NIAID NIH HHS/United States ; R01 AI124214/AI/NIAID NIH HHS/United States ; R01 AI152477/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Clostridioides difficile/*immunology ; Clostridium Infections/*immunology ; Fecal Microbiota Transplantation/methods ; Feces/*microbiology ; Humans ; Immune System/*immunology ; Microbiota/*immunology ; Recurrence ; }, abstract = {Our understanding and utilization of fecal microbiota transplantation (FMT) has jump-started over the past two decades. Recent technological advancements in sequencing and metabolomics have allowed for better characterization of our intestinal microbial counterparts, triggering a surge of excitement in the fields of mucosal immunology and microbiology. This excitement is well founded, as demonstrated by 90% relapse-free cure rates in FMT treatment for recurrent Clostridioides difficile infections. Growing evidence suggests that in addition to bacterial factors, the host immune response during C. difficile infection greatly influences disease severity. In this review, we discuss recent advancements in understanding the interplay between immune cells and the microbiota and how they may relate to recovery from C. difficile through FMT therapy.}, }
@article {pmid32357972, year = {2020}, author = {Uehara, S and Yoneda, N and Higuchi, Y and Yamazaki, H and Suemizu, H}, title = {Human Aldehyde Oxidase 1-Mediated Carbazeran Oxidation in Chimeric TK-NOG Mice Transplanted with Human Hepatocytes.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {48}, number = {7}, pages = {580-586}, doi = {10.1124/dmd.120.091090}, pmid = {32357972}, issn = {1521-009X}, mesh = {Administration, Oral ; Adolescent ; Adult ; Aged ; Aldehyde Oxidase/*metabolism ; Animals ; Biotransformation ; Carbamates/administration &amp; dosage/*pharmacokinetics ; Cells, Cultured ; Child ; Child, Preschool ; Dogs ; Drug Evaluation, Preclinical/methods ; Enzyme Assays ; Feasibility Studies ; Female ; Guinea Pigs ; Hepatocytes/metabolism ; Humans ; Interleukin Receptor Common gamma Subunit/genetics ; Macaca fascicularis ; Male ; Mice ; Mice, Knockout ; Middle Aged ; Oxidation-Reduction ; Rabbits ; Rats ; Recombinant Proteins/metabolism ; Swine ; Swine, Miniature ; Transplantation Chimera/metabolism ; Young Adult ; }, abstract = {Carbazeran is a potent phosphodiesterase inhibitor with species-dependent metabolic profiles in rats, dogs, and humans. In this study, we investigated the aldehyde oxidase (AOX)-mediated oxidation of carbazeran to 4-oxo derivatives in chimeric NOD/Shi-scid IL2 receptor gamma-null mice expressing a herpes simplex virus type 1 thymidine kinase transgene with humanized livers (humanized-liver mice). Liver cytosolic fractions from humanized-liver mouse effectively catalyzed carbazeran 4-oxidation with high affinity for the substrate, similar to those of the human liver cytosolic fractions and recombinant human AOX1 protein. Furthermore, hepatocytes prepared from humanized-liver mice and humans also exhibited substantial metabolism via carbazeran 4-oxidation. After a single oral administration of carbazeran (10 mg/kg), plasma levels of 4-oxo-carbazeran, N-desethyl-4-oxo-carbazeran, and 6,7-dimethoxy-1-[4-(hydroxy)-piperidino]-4-phthalazinone (three human metabolites formed via 4-oxidation) were higher in humanized-liver mice than in the control mice. In contrast, plasma levels of O-desmethylcarbazeran (a major metabolite in dogs) in control mice were higher than those in the humanized-liver mice. Relative excreted amounts of the three 4-oxidation-derived human-specific metabolites in the urine and feces were greater for humanized-liver mice than control mice, whereas the relative excreted amounts of O-desmethylcarbazeran were predominant in the urine and feces of control mice. Thus, the production of carbazeran 4-oxo derivatives was elevated in humanized-liver mice compared with control mice, in agreement with our in vitro enzyme-mediated oxidation data. These results suggest that hepatic human AOX1 functions in humanized-liver mice at the in vivo level and that humanized-liver mice may be useful for predicting drug metabolism in humans, at least with regard to human AOX1-dependent metabolism. SIGNIFICANCE STATEMENT: We found that the production of carbazeran 4-oxo derivatives was higher in humanized-liver mice than in control mice. These results were supported by the fact that carbazeran was rapidly metabolized to 4-oxo-carbazeran in humanized-liver mouse hepatocytes expressing human aldehyde oxidase 1. These results suggest that human aldehyde oxidase 1 is functional in humanized-liver mice in vivo and that chimeric NOD/Shi-scid IL2 receptor gamma-null mice expressing a herpes simplex virus type 1 thymidine kinase transgene transplanted with human hepatocytes may be a suitable model animal for predicting aldehyde oxidase-dependent biotransformation of drugs in humans.}, }
@article {pmid32357144, year = {2020}, author = {Li, Y and Ning, L and Yin, Y and Wang, R and Zhang, Z and Hao, L and Wang, B and Zhao, X and Yang, X and Yin, L and Wu, S and Guo, D and Zhang, C}, title = {Age-related shifts in gut microbiota contribute to cognitive decline in aged rats.}, journal = {Aging}, volume = {12}, number = {9}, pages = {7801-7817}, pmid = {32357144}, issn = {1945-4589}, mesh = {Aging/physiology ; Animals ; Cognition/*physiology ; Cognitive Dysfunction/*metabolism/physiopathology ; Disease Models, Animal ; Gastrointestinal Microbiome/*physiology ; Hippocampus/*metabolism ; *Learning ; Male ; Rats ; }, abstract = {Cognitive function declines during the aging process, meanwhile, gut microbiota of the elderly changed significantly. Although previous studies have reported the effect of gut microbiota on learning and memory, all the reports were based on various artificial interventions to change the gut microbiota without involvement of aging biological characteristics. Here, we investigated the effect of aged gut microbiota on cognitive function by using fecal microbiota transplantation (FMT) from aged to young rats. Results showed that FMT impaired cognitive behavior in young recipient rats; decreased the regional homogeneity in medial prefrontal cortex and hippocampus; changed synaptic structures and decreased dendritic spines; reduced expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor NR1 subunit, and synaptophysin; increased expression of advanced glycation end products (AGEs) and receptor for AGEs (RAGE). All these behavioral, brain structural and functional alterations induced by FMT reflected cognitive decline. In addition, FMT increased levels of pro-inflammatory cytokines and oxidative stress in young rats, indicating that inflammation and oxidative stress may underlie gut-related cognitive decline in aging. This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function.}, }
@article {pmid32356701, year = {2020}, author = {Ciocan, D and Cassard, AM}, title = {[Intestinal bacteria involved in nutritional liver disease killed by phagotherapy: a new therapeutic target].}, journal = {Medecine sciences : M/S}, volume = {36}, number = {4}, pages = {310-312}, doi = {10.1051/medsci/2020052}, pmid = {32356701}, issn = {1958-5381}, mesh = {Animals ; Bacteriophages/physiology ; Ethanol/metabolism ; Fatty Liver, Alcoholic/genetics/microbiology/pathology/therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Genetic Predisposition to Disease ; Humans ; Klebsiella pneumoniae/metabolism/virology ; Liver Diseases/genetics/*microbiology/*therapy ; Mice ; Non-alcoholic Fatty Liver Disease/genetics/microbiology/pathology/therapy ; Nutrition Disorders/complications/genetics/microbiology/prevention &amp; control ; *Phage Therapy/methods ; Saccharomyces/metabolism ; }, }
@article {pmid32356257, year = {2020}, author = {Agrawal, G}, title = {Fecal Microbiota Transplantation for Clostridioides difficile in High-Risk Older Adults: Treat Early, Treat Often.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {12}, pages = {3425-3427}, pmid = {32356257}, issn = {1573-2568}, mesh = {Aged ; Chronic Disease ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid32355268, year = {2020}, author = {Komolmit, P and Oranrap, V and Suksawatamnuay, S and Thanapirom, K and Sriphoosanaphan, S and Srisoonthorn, N and Posuwan, N and Thongmee, T and Treeprasertsuk, S and Poovorawan, Y}, title = {Clinical significance of post-liver transplant hepatitis E seropositivity in high prevalence area of hepatitis E genotype 3: a prospective study.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {7352}, pmid = {32355268}, issn = {2045-2322}, mesh = {Aged ; Cross-Sectional Studies ; Female ; Genotype ; Hepatitis E/*epidemiology/*genetics ; Humans ; Male ; Middle Aged ; Prevalence ; Prospective Studies ; RNA, Viral/genetics ; Seroepidemiologic Studies ; }, abstract = {High hepatitis E (HEV) seroprevalence has been reported in the general population and in post-liver transplant (LT) cases in several regions, including Thailand, with genotype 3 being a predominant genotype. We hypothesized that HEV might persist at a subclinical level and might pose clinical risks in the post-LT period. We performed a cross-sectional study with 108 post-LT patients and found an IgG seroprevalence of 55.6%. Subsequently, 91 cases without clinical evidence of HEV-related hepatitis were enrolled in 1 year of prospective follow-up to determine clinical status, serologies and serum/feces HEV RNA every 4 months. HEV RNA was detected, indicating subclinical infections in patients with or without seropositivity, with an annual incidence of 7.7%. Our results suggest that subclinical HEV infection exists among LT patients in this high-prevalence area. Thus, clinicians should be aware of the possibility of disease reemergence and HEV viral transmission in LT patients.}, }
@article {pmid32354351, year = {2020}, author = {Arnoriaga-Rodríguez, M and Mayneris-Perxachs, J and Burokas, A and Pérez-Brocal, V and Moya, A and Portero-Otin, M and Ricart, W and Maldonado, R and Fernández-Real, JM}, title = {Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {59}, pmid = {32354351}, issn = {2049-2618}, mesh = {Adult ; Aged ; Animals ; *Bacteria/classification/isolation &amp; purification ; Case-Control Studies ; Cross-Sectional Studies ; Endopeptidase Clp/*metabolism ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Obesity/*microbiology ; }, abstract = {BACKGROUND: The chaperone ClpB, a bacterial protein, is a conformational antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH) implicated in body weight regulation in mice. We here investigated the potential associations of gut bacterial ClpB-like gene function with obesity status and gut microbiota in humans.<br><br>RESULTS: Gut microbiota ClpB KEGG function was negatively associated with body mass index, waist circumference, and total fat mass (DEXA). The relative abundance (RA) of several phyla and families directly associated with ClpB was decreased in subjects with obesity. Specifically, the RA of Rikenellaceae, Clostridiaceae and not assigned Firmicutes&#xa0;were lower in subjects with obesity and positively associated with gut bacterial ClpB-like gene function (not assigned Firmicutes (r = 0.405, FDR = 2.93 &#xd7; 10-2), Rikenellaceae (r = 0.217, FDR = 0.031), and Clostridiaceae (r = 0.239, FDR = 0.017)). The gut bacterial ClpB-like gene function was also linked to specific plasma metabolites (hippuric acid and 3-indolepropionic acid) and fecal lupeol. The &#x3b1;-MSH-like epitope similar to that of Escherichia coli ClpB was also identified in some sequences of those bacterial families. After fecal transplantation from humans to mice, the families that more contributed to ClpB-like gene function in humans were also associated with ClpB-like gene function in mice after adjusting for the donor's body mass index (not assigned Firmicutes (r = 0.621, p = 0.003), Prevotellaceae (r = 0.725, p = 4.1 &#xd7; 10[-7]), Rikenellaceae (r = 0.702, p = 3.9 &#xd7; 10[-4]), and Ruminococcaceae (r = 0.526, p = 0.014)). Clostridiaceae (r = - 0.445, p = 0.038) and Prevotellaceae RA (r = - 0.479, p = 0.024) and&#xa0;were also negatively associated with weight gain in mice. The absolute abundance (AA) of Prevotellaceae in mice was also positively associated with the gut bacterial ClpB-like gene function in mice. DESeq2 identified species of Prevotellaceae, both negatively associated with mice' weight gain and positively with gut bacterial ClpB-like gene function.<br><br>CONCLUSIONS: In summary, gut bacterial ClpB-like gene function is associated with obesity status, a specific gut microbiota composition and a plasma&#xa0;metabolomics profile in humans that could be partially transplanted to mice. Video Abstract.}, }
@article {pmid32354259, year = {2020}, author = {Lee, J and d'Aigle, J and Atadja, L and Quaicoe, V and Honarpisheh, P and Ganesh, BP and Hassan, A and Graf, J and Petrosino, J and Putluri, N and Zhu, L and Durgan, DJ and Bryan, RM and McCullough, LD and Venna, VR}, title = {Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice.}, journal = {Circulation research}, volume = {127}, number = {4}, pages = {453-465}, pmid = {32354259}, issn = {1524-4571}, support = {R01 NS094543/NS/NINDS NIH HHS/United States ; TL1 TR003169/TR/NCATS NIH HHS/United States ; R01 NS103592/NS/NINDS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 HL134838/HL/NHLBI NIH HHS/United States ; RF1 AG058463/AG/NIA NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Bifidobacterium longum/metabolism ; Brain Chemistry ; Clostridium symbiosum/metabolism ; Faecalibacterium prausnitzii/metabolism ; Fatty Acids, Volatile/analysis/*biosynthesis/blood ; *Fecal Microbiota Transplantation ; Feces/chemistry ; Gastrointestinal Microbiome/*physiology ; Infarction, Middle Cerebral Artery/*therapy ; Interleukin-17/biosynthesis ; Intestines/chemistry ; Intraepithelial Lymphocytes/physiology ; Ischemic Stroke/*therapy ; Limosilactobacillus fermentum/metabolism ; Male ; Mice ; Mucin-2/metabolism ; Mucin-4/metabolism ; T-Lymphocytes, Regulatory/physiology ; }, abstract = {RATIONALE: The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown.<br><br>OBJECTIVE: To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy.<br><br>METHODS AND RESULTS: Aged male mice (18-20 months) were subjected to ischemic stroke by middle cerebral artery occlusion. We performed fecal transplant gavage 3 days after middle cerebral artery occlusion using young donor biome (2-3 months) or aged biome (18-20 months). At day 14 after stroke, aged stroke mice receiving young fecal transplant gavage had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected 4 SCFA-producers (Bifidobacterium longum, Clostridium symbiosum, Faecalibacterium prausnitzii, and Lactobacillus fermentum) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice.<br><br>CONCLUSIONS: This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host.}, }
@article {pmid32353108, year = {2020}, author = {Payen, M and Nicolis, I and Robin, M and Michonneau, D and Delannoye, J and Mayeur, C and Kapel, N and Berçot, B and Butel, MJ and Le Goff, J and Socié, G and Rousseau, C}, title = {Functional and phylogenetic alterations in gut microbiome are linked to graft-versus-host disease severity.}, journal = {Blood advances}, volume = {4}, number = {9}, pages = {1824-1832}, pmid = {32353108}, issn = {2473-9537}, mesh = {Feces ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/diagnosis/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Phylogeny ; }, abstract = {Acute graft-versus-host disease (aGVHD) is the main complication of hematopoietic stem cell transplantation (HSCT). Changes in gut microbiota composition have been associated with subsequent aGVHD, and reconstitution of healthy microbiota is currently being explored as a therapeutic approach. However, the specific actors in the intestinal ecosystem involved in the pathologic process at the time of aGVHD onset are not yet fully known. We prospectively collected stool samples from patients who underwent allogeneic HSCT. Patients sampled at aGVHD onset were compared with non-GVHD patients. To identify phylogenetic and functional signatures of the disease process, we determined fecal short-chain fatty acid (SFCA) profiles and used high-throughput DNA sequencing and real-time quantitative polymerase chain reaction to assess the microbiota composition. Microbiota alterations were highly specific of gastrointestinal (GI) aGVHD severity. Bacterial biomass and α-diversity were lower in severe aGVHD. We identified several bacterial signatures associated with severe aGVHD at disease onset; a negative correlation was observed with anaerobic bacteria of the Lachnospiraceae, especially the Blautia genus, and Ruminococcaceae families. In parallel, in severe aGVHD patients, we showed a dramatic decrease in the levels of the main SFCAs: acetate (75.8%), propionate (95.8%), and butyrate (94.6%). Mild aGVHD patients were characterized by conserved levels of propionate and Blautia propionate producers. Butyrate was significantly decreased in all GI aGVHD stages, representing a potential diagnostic marker of the disease. Specific microbiota and metabolic alterations were thus associated with aGVHD severity and may be useful for diagnostic and pathophysiologic purposes.}, }
@article {pmid32350099, year = {2020}, author = {Korach-Rechtman, H and Hreish, M and Fried, C and Gerassy-Vainberg, S and Azzam, ZS and Kashi, Y and Berger, G}, title = {Intestinal Dysbiosis in Carriers of Carbapenem-Resistant Enterobacteriaceae.}, journal = {mSphere}, volume = {5}, number = {2}, pages = {}, pmid = {32350099}, issn = {2379-5042}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carbapenem-Resistant Enterobacteriaceae/drug effects/genetics/*pathogenicity ; Carbapenems/pharmacology ; Carrier State/*microbiology ; Cohort Studies ; Dysbiosis/*microbiology ; Enterobacteriaceae Infections/microbiology/*physiopathology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Intestines/microbiology/*physiopathology ; Male ; Metabolic Networks and Pathways ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Young Adult ; }, abstract = {Infection with carbapenem-resistant Enterobacteriaceae (CRE) has become an important challenge in health care settings and a growing concern worldwide. Since infection is preceded by colonization, an understanding of the latter may reduce CRE infections. We aimed to characterize the gut microbiota in CRE carriers, assuming that microbiota alterations precede CRE colonization. We evaluated the gut microbiota using 16S rRNA gene sequencing extracted of fecal samples collected from hospitalized CRE carriers and two control groups, hospitalized noncarriers and healthy adults. The microbiota diversity and composition in CRE-colonized patients differed from those of the control group participants. These CRE carriers displayed lower phylogenetic diversity and dysbiotic microbiota, enriched with members of the family Enterobacteriaceae Concurrent with the enrichment in Enterobacteriaceae, a depletion of anaerobic commensals was observed. Additionally, changes in several predicted metabolic pathways were observed for the CRE carriers. Concomitantly, we found higher prevalence of bacteremia in the CRE carriers. Several clinical factors that might induce changes in the microbiota were examined and found to be insignificant between the groups. The compositional and functional changes in the microbiota of CRE-colonized patients are associated with increased risk for systemic infection. Our study results provide justification for attempts to restore the dysbiotic microbiota with probiotics or fecal transplantation.IMPORTANCE The gut microbiota plays important roles in the host's normal function and health, including protection against colonization by pathogenic bacteria. Alterations in the gut microbial profile can potentially serve as an early diagnostic tool, as well as a therapeutic strategy against colonization by and carriage of harmful bacteria, including antibiotic-resistant pathogens. Here, we show that the microbiota of hospitalized patients demonstrated specific taxa which differed between carriers of carbapenem-resistant Enterobacteriaceae (CRE) and noncarriers. The difference in the microbiota also dictates alterations in microbiome-specific metabolic capabilities, in association with increased prevalence of systemic infection. Reintroducing specific strains and/or correction of dysbiosis with probiotics or fecal transplantation may potentially lead to colonization by bacterial taxa responsible for protection against or depletion of antibiotic-resistant pathogens.}, }
@article {pmid32349423, year = {2020}, author = {Nowland, TL and Torok, VA and Low, WY and Barton, MD and Plush, KJ and Kirkwood, RN}, title = {Faecal Microbiota Analysis of Piglets During Lactation.}, journal = {Animals : an open access journal from MDPI}, volume = {10}, number = {5}, pages = {}, pmid = {32349423}, issn = {2076-2615}, support = {2018094//Department of Agriculture and Water Resources, Australian Government/ ; }, abstract = {Antimicrobial use in animals and the potential development of antimicrobial resistance is a global concern. So, non-antimicrobial techniques for animal disease control are needed. This study aimed to determine whether neonatal ceftiofur (CF) treatment affects piglet faecal microbiomes and whether faecal microbiome transplantation (FMT) can correct it. Two focal piglets per sow were assigned to treatments as follows: cffresh (n = 6) received CF (3 mg/kg intramuscular) at 7 d and fresh FMT at 13 d; cffrozen (n = 7) received CF at 7 d and frozen FMT at 13 d; CF (n = 8) received CF at 7 d and no FMT; and no CF (n = 5) received no CF or FMT. DNA was extracted from faecal samples collected on days 7, 13, and 18 for 16S rRNA amplicon analysis. All faecal blends used for the FMT consisted of pooled donor pig faeces at 1:2 ratio with saline, delivered orally at 3 mL/kg. Alpha and beta diversity metrics increased with age (p < 0.05). However, no effect of antibiotic or FMT treatment was evident in 13 and 18 d old piglets (p > 0.05). Although no effect of treatment was observed, information regarding microbial membership during lactation was gained.}, }
@article {pmid32346376, year = {2020}, author = {Zhang, Y and Liu, Q and Yu, Y and Wang, M and Wen, C and He, Z}, title = {Early and Short-Term Interventions in the Gut Microbiota Affects Lupus Severity, Progression, and Treatment in MRL/lpr Mice.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {628}, pmid = {32346376}, issn = {1664-302X}, abstract = {There have been attempts to reveal the possible associations between systemic lupus erythematosus (SLE) and gut microbiota. Using MRL/lpr mice, this study was performed to reveal whether early and short-term interventions in gut microbiota affect lupus. MRL/lpr mice were treated with antibiotics or fecal microbiota transplantation (FMT) before onset. Then, prednisone was used to treat the lupus mice with initially different gut microbiota compositions. The compositions of gut microbiota were assessed by the V3-V4 region of 16S rRNA gene sequence. Early and short-term antibiotics exposure aggravated lupus severity by depleting beneficial gut microbiota for lupus, such as Lactobacillus and Bifidobacterium, and enriching harmful gut microbiota for lupus, such as Klebsiella and Proteus. FMT alleviated lupus severity by renovating the antibiotic-induced dysbiosis of gut microbiota in the following 1 week after antibiotics exposure. Besides, short-term antibiotics exposure before onset imposed no significant effects on lupus progression, but the following one week of FMT suppressed lupus progression. Moreover, the short-term antibiotics or FMT before onset inhibited the therapeutic efficiency of prednisone on lupus from 9 to 13 weeks old of MRL/lpr mice. These data demonstrate that the gut microbiota before onset is important for lupus severity, progression and treatment.}, }
@article {pmid32346208, year = {2020}, author = {Soo, WT and Bryant, RV and Costello, SP}, title = {Faecal microbiota transplantation: indications, evidence and safety.}, journal = {Australian prescriber}, volume = {43}, number = {2}, pages = {36-38}, pmid = {32346208}, issn = {0312-8008}, abstract = {The human gut contains many species of microorganisms, many of which have a role in maintaining good health. The gut microbiota can be affected by diet, diseases and drugs, especially antibiotics. Faecal microbiota transplantation involves transplanting faecal material from a healthy person to a patient, with the aim of treating disease. It is a recommended treatment option for patients with recurrent or refractory Clostridioides difficile as it has a cure rate over 90%. There is evidence that faecal microbiota transplantation can induce remission in ulcerative colitis, however maintenance of remission data are lacking. For other diseases it currently should not be used outside a clinical trial. Stool donors have to be healthy and are screened for a range of diseases. As faecal material is usually transplanted during colonoscopy, the recipient must have bowel preparation before the procedure. Adverse effects are mainly gastrointestinal and usually resolve in the week following transplantation. There are limited data on long-term safety.}, }
@article {pmid32344895, year = {2020}, author = {Kiss, B and Mikó, E and Sebő, &#xc9; and Toth, J and Ujlaki, G and Szabó, J and Uray, K and Bai, P and Árkosy, P}, title = {Oncobiosis and Microbial Metabolite Signaling in Pancreatic Adenocarcinoma.}, journal = {Cancers}, volume = {12}, number = {5}, pages = {}, pmid = {32344895}, issn = {2072-6694}, support = {K123975//Hungarian Scientific Research Fund/ ; PD124110//Hungarian Scientific Research Fund/ ; FK128387//Hungarian Scientific Research Fund/ ; GINOP-2.3.2-15-2016-00006//Hungarian Scientific Research Fund/ ; EFOP-3.6.2-16-2017-0006//Hungarian Scientific Research Fund/ ; K120669//Hungarian Scientific Research Fund/ ; Bolyai fellowship//Magyar Tudom&#xe1;nyos Akad&#xe9;mia/ ; NKFIH-1150-6/2019//Hungarian Scientific Research Fund/ ; &#xda;NKP-19-4-DE-79//Hungarian Scientific Research Fund/ ; }, abstract = {Pancreatic adenocarcinoma is one of the most lethal cancers in both men and women, with a median five-year survival of around 5%. Therefore, pancreatic adenocarcinoma represents an unmet medical need. Neoplastic diseases, such as pancreatic adenocarcinoma, often are associated with microbiome dysbiosis, termed oncobiosis. In pancreatic adenocarcinoma, the oral, duodenal, ductal, and fecal microbiome become dysbiotic. Furthermore, the pancreas frequently becomes colonized (by Helicobacter pylori and Malassezia, among others). The oncobiomes from long- and short-term survivors of pancreatic adenocarcinoma are different and transplantation of the microbiome from long-term survivors into animal models of pancreatic adenocarcinoma prolongs survival. The oncobiome in pancreatic adenocarcinoma modulates the inflammatory processes that drive carcinogenesis. In this review, we point out that bacterial metabolites (short chain fatty acids, secondary bile acids, polyamines, indole-derivatives, etc.) also have a role in the microbiome-driven pathogenesis of pancreatic adenocarcinoma. Finally, we show that bacterial metabolism and the bacterial metabolome is largely dysregulated in pancreatic adenocarcinoma. The pathogenic role of additional metabolites and metabolic pathways will be identified in the near future, widening the scope of this therapeutically and diagnostically exploitable pathogenic pathway in pancreatic adenocarcinoma.}, }
@article {pmid32344807, year = {2020}, author = {Janahi, EM and Parkar, SFD and Mustafa, S and Eisa, ZM}, title = {Implications of Hepatitis E Virus in Blood Transfusions, Hemodialysis, and Solid Organ Transplants.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {56}, number = {5}, pages = {}, pmid = {32344807}, issn = {1648-9144}, mesh = {Blood Transfusion/*methods/trends ; Hepatitis E/*complications/physiopathology ; Hepatitis E virus/pathogenicity ; Humans ; Organ Transplantation/methods/*trends ; Renal Dialysis/*methods/trends ; }, abstract = {Hepatitis E Virus (HEV) is emerging as the primary cause of acute viral hepatitis in humans. The virus is commonly transmitted by the fecal-oral route via contaminated water in endemic regions or through the consumption of inadequately cooked swine products or game meats in industrialized regions. HEV genotypes 1 and 2 are predominantly associated with waterborne transmission in developing countries, whereas HEV3 and HEV4 are mainly zoonotically transmitted in industrialized countries. Seroprevalence in populations determined by detecting anti-HEV antibodies and serum HEV RNA is commonly used to analyze the presence of HEV. Although HEV RNA-based detection is now standardized, there is a lack of agreement between the assaying methods used for gathering seroprevalence data. Since 2004, HEV has been considered as a transmissible infectious agent through blood transfusion. Recent seroprevalence studies in European countries indicate an underestimated risk for blood transfusion and hence warrant testing the blood supply. HEV infection is usually self-limiting and spontaneously cleared. However, in about 60% of recipients of solid organ transplants, HEV progresses to chronic hepatitis. Immunosuppressive drugs such as tacrolimus are a major cause of chronic hepatitis and reducing its dosage results in viral clearance in about 30% of patients. In hemodialysis patients, the parenteral route is implicated as an important mechanism of transmission. In this review, we explore the clinical and epidemiological characteristics of various HEV genotypes in blood donors, hemodialysis patients, and transplant recipients.}, }
@article {pmid32343000, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Randomised clinical trial: faecal microbiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel syndrome.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {51}, number = {12}, pages = {1321-1331}, doi = {10.1111/apt.15740}, pmid = {32343000}, issn = {1365-2036}, mesh = {Adolescent ; Adult ; Aged ; Colonoscopy/*methods ; Double-Blind Method ; Dysbiosis/complications/microbiology/therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/physiology ; Humans ; Irritable Bowel Syndrome/complications/microbiology/*therapy ; Male ; Middle Aged ; Placebos ; Quality of Life ; Transplantation, Autologous ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) has been associated with microbial dysbiosis.<br><br>AIM: To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of IBS.<br><br>METHODS: Forty-nine IBS patients were randomised to receive autologous or allogenic FMT via colonoscopy. The primary endpoint was a sustained, minimum of 50-point, reduction in the IBS Symptom Severity Score. The secondary outcomes were levels of anxiety and depression, changes in quality of life, gut microbiota and faecal water content as assessed with validated questionnaires, intestinal microbiota composition and stool dry weight.<br><br>RESULTS: The primary endpoint was not achieved in either group. However, there was a transient reduction in the mean IBS Symptom Severity Score in the FMT group at 12&#xa0;weeks after treatment as compared to baseline (P&#xa0;=&#xa0;0.01). The groups did not differ in the number of patients achieving clinical response at 12&#xa0;weeks. In the FMT-treated patients, microbial composition had changed to resemble that of the donor and the stool water content decreased significantly compared to baseline. The depression score decreased in patients with a reduction in IBS symptoms after FMT, but not in those placebo-treated patients who experienced a reduction in IBS symptoms.<br><br>CONCLUSIONS: FMT provided only a transient relief of symptoms, although it induced a sustained alteration in the microbiota of IBS patients. Therefore, FMT delivered by a single infusion via colonoscopy cannot be recommended as a treatment for IBS in clinical practice. ClinicalTrials.Org, Trial registration number: NCT03561519.}, }
@article {pmid32341472, year = {2020}, author = {Hu, X and Guo, J and Zhao, C and Jiang, P and Maimai, T and Yanyi, L and Cao, Y and Fu, Y and Zhang, N}, title = {The gut microbiota contributes to the development of Staphylococcus aureus-induced mastitis in mice.}, journal = {The ISME journal}, volume = {14}, number = {7}, pages = {1897-1910}, pmid = {32341472}, issn = {1751-7370}, mesh = {Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; *Mastitis ; Mice ; Staphylococcus aureus ; }, abstract = {Mastitis is one of the most prevalent diseases in dairy farming worldwide. The gut microbiota plays an important role in the regulation of systemic and local inflammatory diseases, such as mastitis. However, the regulatory mechanism of the gut microbiota on mastitis is still unclear. Thus, the aim of this study was to investigate the function and regulatory mechanisms of the gut microbiota in host defense against mastitis caused by Staphylococcus aureus (S. aureus) infection. Increased blood-milk barrier permeability, and S. aureus-induced mastitis severity were observed gut microbiota-dysbiosis mice compared with those in control mice. Moreover, feces microbiota transplantation (FMT) to microbbiota-dysbiosis mice reversed these effects. Furthermore, established disruption of commensal homeostasis results in significantly increased abundance of pathogenic Enterobacter bacteria, while the relative abundance of short-chain fatty acid (SCFAs)-producing bacterial phyla (Firmicutes and Bacteroidetes) was significantly reduced. However, FMT to gut microbiota-dysbiosis mice reversed these changes. In addition, dysbiosis reduced the levels of SCFAs, and administration of sodium propionate, sodium butyrate, and probiotics (butyrate-producing bacteria) reversed the changes in the blood-milk barrier and reduced the severity of mastitis induced by S. aureus. In conclusion, this new finding demonstrated that the gut microbiota acts as a protective factor in host defense against mastitis and that targeting the gut-mammary gland axis represents a promising therapeutic approach for mastitis treatment.}, }
@article {pmid32340697, year = {2020}, author = {Dumas, E and Venken, K and Rosenbaum, JT and Elewaut, D}, title = {Intestinal Microbiota, HLA-B27, and Spondyloarthritis: Dangerous Liaisons.}, journal = {Rheumatic diseases clinics of North America}, volume = {46}, number = {2}, pages = {213-224}, doi = {10.1016/j.rdc.2020.01.007}, pmid = {32340697}, issn = {1558-3163}, mesh = {Disease Progression ; *Gastrointestinal Microbiome/genetics/immunology ; *HLA-B27 Antigen/genetics/immunology ; Humans ; *Spondylarthritis/complications/genetics/immunology ; }, abstract = {Spondyloarthritis, although primarily a joint-centered disease, is associated with extra-articular features, such as gut inflammation, psoriasis, and/or uveitis. Evidence points to underlying genetic predisposing factors and/or environmental factors. This is most clear in the gut, with progress through 16S and metagenomics sequencing studies and the results of functional studies in preclinical arthritis models. Translation of these findings to the clinic is making progress based on encouraging results of fecal microbial transplant studies in several human diseases. This review elaborates on novel trends in host-microbial interplay in spondyloarthritis, focusing on microbiota, immune dysregulation, and disease progression, and modulation by HLA-B27.}, }
@article {pmid32336953, year = {2020}, author = {Kaur, A and Goggolidou, P}, title = {Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies.}, journal = {Journal of inflammation (London, England)}, volume = {17}, number = {}, pages = {15}, pmid = {32336953}, issn = {1476-9255}, abstract = {Dynamic interactions between the gastrointestinal epithelium and the mucosal immune system normally contribute to ensuring intestinal homeostasis and optimal immunosurveillance, but destabilisation of these interactions in genetically predisposed individuals can lead to the development of chronic inflammatory diseases. Ulcerative colitis is one of the main types of inflammatory diseases that affect the bowel, but its pathogenesis has yet to be completely defined. Several genetic factors and other inflammation-related genes are implicated in mediating the inflammation and development of the disease. Some susceptibility loci associated with increased risk of ulcerative colitis are found to be implicated in mucosal barrier function. Different biomarkers that cause damage to the colonic mucosa can be detected in patients, including perinuclear ANCA, which is also useful in distinguishing ulcerative colitis from other colitides. The choice of treatment for ulcerative colitis depends on disease severity. Therapeutic strategies include anti-tumour necrosis factor alpha (TNF-α) monoclonal antibodies used to block the production of TNF-α that mediates intestinal tract inflammation, an anti-adhesion drug that prevents lymphocyte infiltration from the blood into the inflamed gut, inhibitors of JAK1 and JAK3 that suppress the innate immune cell signalling and interferons α/β which stimulate the production of anti-inflammatory cytokines, as well as faecal microbiota transplantation. Although further research is still required to fully dissect the pathophysiology of ulcerative colitis, understanding its cellular pathology and molecular mechanisms has already proven beneficial and it has got the potential to identify further novel, effective targets for therapy and reduce the burden of this chronic disease.}, }
@article {pmid32330797, year = {2020}, author = {Wang, H and Zhang, S and Yang, F and Xin, R and Wang, S and Cui, D and Sun, Y}, title = {The gut microbiota confers protection in the CNS against neurodegeneration induced by manganism.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {127}, number = {}, pages = {110150}, doi = {10.1016/j.biopha.2020.110150}, pmid = {32330797}, issn = {1950-6007}, mesh = {Animals ; Central Nervous System/drug effects ; Dysbiosis/*complications ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Male ; Manganese/*toxicity ; Neurotoxicity Syndromes/*etiology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Among all types of pollution, heavy metals are considered the greatest threat to human health, and heavy metals are associated with an increased risk of cardiovascular disease, coronary heart disease and neurodegenerative disorders. Manganese (Mn) exposure is well reported to exert neurotoxicity and various neurodegenerative disorders, but the mechanisms are not clear. The gut microbiota plays a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities. The changes in chemical signaling, metabolism and gut microbiota associated with Mn exposure have provided deeper insight into the neurotoxic mechanism of Mn. We observed that Mn exposure increases host manganic bioaccumulation, and β-amyloid (Aβ), receptor-interacting protein kinase 3 (RIP3) and caspase-3 production in the brain, and causes hippocampal degeneration and necrosis. Mn exposure led to decreased gut bacterial richness, especially for Prevotellaceae, Fusobacteriaceae and Lactobacillaceae. In addition, Mn exposure altered the metabolism of tryptamine, taurodeoxycholic acid, β-hydroxypyruvic acid and urocanic acid. Meanwhile, we found correlations between the abundance of certain bacterial species and the level of tryptamine, taurodeoxycholic acid, β-hydroxypyruvic acid and urocanic acid. Fecal microbiome transplantation from normal rats could alleviate the neurotoxicity of Mn exposure by shaping the gut microbiota. Our findings highlight the role of gut dysbiosis-promoted neurotoxicity in Mn exposure and suggest a novel therapeutic strategy of remodeling the gut microbiota.}, }
@article {pmid32330729, year = {2020}, author = {Zhang, A and Sodhi, CP and Wang, M and Shores, DR and Fulton, W and Prindle, T and Brosten, S and O'Hare, E and Lau, A and Ding, H and Jia, H and Lu, P and White, JR and Hui, J and Sears, CL and Hackam, DJ and Alaish, SM}, title = {A Central Role for Lipocalin-2 in the Adaptation to Short-Bowel Syndrome Through Down-Regulation of IL22 in Mice.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {10}, number = {2}, pages = {309-326}, pmid = {32330729}, issn = {2352-345X}, mesh = {Adaptation, Physiological/*immunology ; Animals ; Disease Models, Animal ; Down-Regulation/immunology ; Humans ; Interleukins/genetics/*metabolism ; Intestinal Mucosa/immunology/pathology ; Intestine, Small/immunology/pathology ; Lipocalin-2/genetics/*metabolism ; Male ; Mice ; Mice, Knockout ; Permeability ; Short Bowel Syndrome/immunology/pathology/*physiopathology ; Interleukin-22 ; }, abstract = {BACKGROUND &amp; AIMS: In short-bowel syndrome (SBS), inadequate intestinal adaptation is responsible for the majority of complications, including sepsis, liver failure, and death. In this study, we sought to further delineate the adaptive response to identify potential therapeutic targets.<br><br>METHODS: We performed a 75% small-bowel resection (SBR) or sham operation on C57Bl/6J wild-type (WT), lipocalin-2 (LCN2)[-/-], and interleukin 22 (IL22)[-/-] mice. Exogenous IL22 was administered to SBR WT mice. Cecal fecal matter from SBR WT and SBR LCN2[-/-] mice were transplanted into germ-free mice. Intestinal permeability, inflammation, proliferation, and the microbiome were evaluated 1 week after surgery. CD4[+]IL22[+] laminal propria lymphocytes were sorted by flow cytometry. Na&#xef;ve T cells were polarized to T-helper cells with or without LCN2.<br><br>RESULTS: A 75% SBR in a mouse re-creates the increased intestinal permeability, enterocyte proliferation, and intestinal dysbiosis seen in SBS. LCN2 expression increases after 75% SBR, and this increase can be abrogated with broad-spectrum antibiotic treatment. LCN2[-/-] mice have less intestinal inflammation, increased IL22 expression, and greater adaptation as evidenced by less intestinal permeability, increased carbohydrate enzyme expression, less weight loss, and less dysbiosis after 75% SBR than WT mice. The proinflammatory and anti-adaptive effects of LCN2 can be transferred to germ-free mice via a fecal transplant. Administration of exogenous IL22 improves adaptation and restores the normal microbiome after 75% SBR in WT mice.<br><br>CONCLUSIONS: LCN2 promotes inflammation and slows intestinal adaptation through changes in the microbiome and IL22 inhibition in a mouse SBS model. Strategies to reduce LCN2 may offer novel therapeutic approaches to enhance adaptation in SBS.}, }
@article {pmid32330075, year = {2020}, author = {Nie, X and Li, L and Yi, M and Qin, W and Zhao, W and Li, F and Wu, B and Yuan, X}, title = {The Intestinal Microbiota Plays as a Protective Regulator Against Radiation Pneumonitis.}, journal = {Radiation research}, volume = {194}, number = {1}, pages = {52-60}, doi = {10.1667/RR15579.1}, pmid = {32330075}, issn = {1938-5404}, mesh = {Animals ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*radiation effects ; Mice ; Mice, Inbred C57BL ; Radiation Pneumonitis/metabolism/*microbiology/*prevention &amp; control ; Tissue Plasminogen Activator/metabolism ; }, abstract = {Radiation pneumonitis is a common complication of thoracic irradiation for lung cancer patients. The healthy gut microbiota plays an important role in the local mucosal defense process as well as pulmonary immunomodulation of the host. However, the effect of the intestinal microbiota on radiation pneumonitis is not well understood. Here we studied how the intestinal microbiota affected the host response to radiation pneumonitis. C57BL/6 mice were administered antibiotics to induce disequilibrium in the gut microbiota, and subsequently irradiated. We found that the intestinal microbiota served as a protective mediator against radiation pneumonitis, as indicated by decreased body weight and increased mortality in antibiotic-treated mice. In mice with gut microbiota disequilibrium, more serious pathological lung damage was observed at two and four weeks postirradiation. Fecal microbiota transplantation into irradiated mice led to improvement from radiation-induced inflammation two weeks postirradiation. High-throughput sequencing of murine feces displayed conversion of flora diversity, bacterial composition and community structure in the absence of normal intestinal flora. We filtered the potentially important species among the gut microbiota and considered that the tissue-type plasminogen activator might be involved in the inflammatory process. This study reveals that the gut microbiota functions as a protective regulator against radiation pneumonitis. Additionally, fecal microbiota transplantation was shown to alleviate lung injury in the irradiated model. The protective role of the healthy gut microbiota and the utilization of the gut-lung axis show potential for innovative therapeutic strategies in radiation-induced lung injury.}, }
@article {pmid32327518, year = {2020}, author = {George, U and Simsek, C and Faleye, TOC and Arowolo, O and Oragwa, A and Adewumi, OM and Matthijnssens, J and Adeniji, JA}, title = {Genome Sequences of Novel Members of Previously Described DNA and RNA Virus Families, Isolated from Feces of a Drill Monkey in Nigeria.}, journal = {Microbiology resource announcements}, volume = {9}, number = {17}, pages = {}, pmid = {32327518}, issn = {2576-098X}, abstract = {The genomes of seven novel members of previously described DNA and RNA virus families are described here. These viruses were recovered using a viral metagenomic approach from the stool of a drill monkey (Mandrillus leucophaeus) housed in a sanctuary in Cross River State, Nigeria.}, }
@article {pmid32326509, year = {2020}, author = {Nicco, C and Paule, A and Konturek, P and Edeas, M}, title = {From Donor to Patient: Collection, Preparation and Cryopreservation of Fecal Samples for Fecal Microbiota Transplantation.}, journal = {Diseases (Basel, Switzerland)}, volume = {8}, number = {2}, pages = {}, pmid = {32326509}, issn = {2079-9721}, abstract = {Fecal Microbiota Transplantation (FMT) is suggested as an efficacious therapeutic strategy for restoring intestinal microbial balance, and thus for treating disease associated with alteration of gut microbiota. FMT consists of the administration of fresh or frozen fecal microorganisms from a healthy donor into the intestinal tract of diseased patients. At this time, in according to healthcare authorities, FMT is mainly used to treat recurrent Clostridium difficile. Despite the existence of a few existing stool banks worldwide and many studies of the FMT, there is no standard method for producing material for FMT, and there are a multitude of factors that can vary between the institutions. The main constraints for the therapeutic uses of FMT are safety concerns and acceptability. Technical and logistical issues arise when establishing such a non-standardized treatment into clinical practice with safety and proper governance. In this context, our manuscript describes a process of donor safety screening for FMT compiling clinical and biological examinations, questionnaires and interviews of donors. The potential risk of transmission of SARS-CoV-2 virus by the use of fecal microbiota for transplantation must be taken urgently into consideration. We discuss a standardized procedure of collection, preparation and cryopreservation of fecal samples through to the administration of material to patients, and explore the risks and limits of this method of FMT. The future success of medicine employing microbiota transplantation will be tightly related to its modulation and manipulation to combat dysbiosis. To achieve this goal, standard and strict methods need to be established before performing any type of FMT.}, }
@article {pmid32324085, year = {2020}, author = {Bahl, MI and Jørgensen, SMD and Skriver, AH and Larsen, NA and Wang, M and Licht, TR and Dahlerup, JF and Hvas, CL}, title = {Faecal microbiota transplantation for eradication of co-infection with Clostridioides difficile and extensively drug-resistant KPC-producing Klebsiella pneumoniae.}, journal = {Scandinavian journal of gastroenterology}, volume = {55}, number = {5}, pages = {626-630}, doi = {10.1080/00365521.2020.1753806}, pmid = {32324085}, issn = {1502-7708}, mesh = {Aged ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Coinfection/microbiology/*therapy ; Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Klebsiella Infections/microbiology/*therapy ; Klebsiella pneumoniae/isolation &amp; purification ; }, abstract = {Clostridioides difficile infection may be complicated by co-infection with other pathogens. We here describe the successful use of faecal microbiota transplantation to eradicate concomitant C. difficile and extensively drug-resistant (XDR) KPC-producing Klebsiella pneumoniae. Donor microbiota efficiently engrafted in the patient, and a donor-like microbial assemblage persisted in the patient during six months follow-up. The report explores the potential for the donor microbiota to eradicate and replace multi-resistant microorganisms.}, }
@article {pmid32323220, year = {2020}, author = {Pourang, A and Mesinkovska, NA}, title = {New and Emerging Therapies for Alopecia Areata.}, journal = {Drugs}, volume = {80}, number = {7}, pages = {635-646}, pmid = {32323220}, issn = {1179-1950}, mesh = {Alopecia Areata/*drug therapy/metabolism ; Animals ; Antibodies, Monoclonal, Humanized/adverse effects/*pharmacology ; Humans ; Janus Kinase Inhibitors/adverse effects/*pharmacology ; Janus Kinases/*antagonists &amp; inhibitors/metabolism ; Ustekinumab/adverse effects/*pharmacology ; }, abstract = {Alopecia areata (AA) is an autoimmune condition that affects up to 2% of the general population. Currently available treatment options for AA are of limited efficacy and can be associated with adverse effects. The advancement in understanding of the genetic and molecular mechanisms of AA has led to the development of novel treatment options, with the Janus kinase (JAK) inhibitor class of drugs at the forefront of ongoing clinical trials. Platelet-rich plasma, fecal transplants, and cytokine-targeted therapy with ustekinumab and dupilumab have also been shown to regrow hair in patients with AA in individual case reports or small studies. Several other novel therapies have preliminary data or are being tested in clinical trials.}, }
@article {pmid32323005, year = {2020}, author = {Ylinen, E and Salmenlinna, S and Halkilahti, J and Jahnukainen, T and Korhonen, L and Virkkala, T and Rimhanen-Finne, R and Nuutinen, M and Kataja, J and Arikoski, P and Linkosalo, L and Bai, X and Matussek, A and Jalanko, H and Saxén, H}, title = {Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli in children: incidence, risk factors, and clinical outcome.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {35}, number = {9}, pages = {1749-1759}, pmid = {32323005}, issn = {1432-198X}, mesh = {Adolescent ; Age Factors ; Child ; Child, Preschool ; Creatinine/blood ; Female ; Hemolytic-Uremic Syndrome/*epidemiology/microbiology/therapy ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Renal Dialysis/statistics &amp; numerical data ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Shiga-Toxigenic Escherichia coli/isolation &amp; purification ; }, abstract = {BACKGROUND: Hemolytic uremic syndrome (HUS) is a multisystemic disease. In a nationwide study, we characterized the incidence, clinical course, and prognosis of HUS caused by Shiga toxin (Stx)-producing Escherichia coli (STEC) strains with emphasis on risk factors, disease severity, and long-term outcome.<br><br>METHODS: The data on pediatric HUS patients from 2000 to 2016 were collected from the medical records. STEC isolates from fecal cultures of HUS and non-HUS patients were collected from the same time period and characterized by whole genome sequencing analysis.<br><br>RESULTS: Fifty-eight out of 262 culture-positive cases developed verified (n&#xa0;=&#x2009;58, 22%) STEC-HUS. Another 29 cases had probable STEC-HUS, the annual incidence of STEC-HUS being 0.5 per 100,000 children. Eleven different serogroups were detected, O157 being the most common (n&#xa0;=&#x2009;37, 66%). Age under 3&#xa0;years (OR 2.4), stx2 (OR 9.7), and stx2a (OR 16.6) were found to be risk factors for HUS. Fifty-five patients (63%) needed dialysis. Twenty-nine patients (33%) developed major neurological symptoms. Complete renal recovery was observed in 57 patients after a median 4.0&#xa0;years of follow-up. Age under 3&#xa0;years, leukocyte count over 20&#x2009;&#xd7;&#x2009;10[9]/L, and need for dialysis were predictive factors for poor renal outcome.<br><br>CONCLUSIONS: Age under 3&#xa0;years, stx2, and stx2a were risk factors for HUS in STEC-positive children. However, serogroup or stx types did not predict the renal outcome or major CNS symptoms.}, }
@article {pmid32319703, year = {2020}, author = {Vangoitsenhoven, R and Cresci, GAM}, title = {Role of Microbiome and Antibiotics in Autoimmune Diseases.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {35}, number = {3}, pages = {406-416}, doi = {10.1002/ncp.10489}, pmid = {32319703}, issn = {1941-2452}, support = {R00AA023266//GAC National Institutes of Health, NIAAA/ ; }, mesh = {Animals ; *Anti-Bacterial Agents/adverse effects/therapeutic use ; *Autoimmune Diseases/drug therapy/microbiology/therapy ; Diabetes Mellitus, Type 1/immunology/microbiology ; Dysbiosis/chemically induced/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/immunology/*physiology ; Humans ; Immune System/drug effects/microbiology/physiology ; Inflammatory Bowel Diseases/immunology/microbiology ; Lymphoid Tissue/immunology/microbiology ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The global rise in the incidence of autoimmune diseases has paralleled the widespread use of antibiotics. Recently, the gut microbiome has been shown to be key in the development and maturation of a normal immune system, and a range of microbial disturbances have been associated with the development and activity of several autoimmune diseases. Here, we aim to provide an overview of the mechanistic crosstalk between the human microbiome, the immune system, and antibiotics. The disease-associated microbial gut dysbiosis, the potential role of antibiotics in the development and treatment of autoimmune diseases, and the manipulation of the gut microbiome with prebiotics and probiotics is discussed using 2 key autoimmune diseases as an example: inflammatory bowel disease and type 1 diabetes. Although some data suggest that widespread use of antibiotics may facilitate autoimmunity through gut dysbiosis, there are also data to suggest antibiotics may hold the potential to improve disease activity. Currently, the effect of fecal microbiota transplantation on several autoimmune diseases is being studied in clinical trials, and several preclinical studies are revealing promising results with probiotic and prebiotic therapies.}, }
@article {pmid32319196, year = {2020}, author = {Takashima, S and Tanaka, F and Kawaguchi, Y and Usui, Y and Fujimoto, K and Nadatani, Y and Otani, K and Hosomi, S and Nagami, Y and Kamata, N and Taira, K and Tanigawa, T and Watanabe, T and Imoto, S and Uematsu, S and Fujiwara, Y}, title = {Proton pump inhibitors enhance intestinal permeability via dysbiosis of gut microbiota under stressed conditions in mice.}, journal = {Neurogastroenterology and motility}, volume = {32}, number = {7}, pages = {e13841}, doi = {10.1111/nmo.13841}, pmid = {32319196}, issn = {1365-2982}, mesh = {Animals ; Corticosterone/blood ; Dysbiosis/*chemically induced ; Gastrointestinal Microbiome/*drug effects ; Intestinal Mucosa/*drug effects/*metabolism ; Male ; Mice, Inbred C57BL ; Permeability/drug effects ; Proton Pump Inhibitors/*administration &amp; dosage ; Rabeprazole/*administration &amp; dosage ; Stress, Psychological/blood/*metabolism ; }, abstract = {BACKGROUND: Intestinal permeability and psychological stress are considered the key mechanism(s) in functional dyspepsia (FD). Although proton pump inhibitors (PPIs) are commonly used for the treatment of FD, the effect of PPIs on intestinal permeability has not been elucidated. This study investigated the effect of PPI on intestinal permeability under stressed conditions.<br><br>METHODS: C57BL/6J mice were subjected to water avoidance stress (WAS) and administered rabeprazole (40&#xa0;mg/kg) or vehicle treatment (VT). We then evaluated intestinal permeability both in vivo and ex vivo using plasma fluorescein isothiocyanate-dextran and by assessing the paracellular permeability and transepithelial electrical resistance (TEER) in an Ussing chamber, respectively. Furthermore, we evaluated the effect of PPI-treated fecal microbiota transplant (FMT) on intestinal permeability in vivo. Microbiota profiles of donor feces were assessed by 16S rRNA gene analysis using MiSeq and QIIME2.<br><br>KEY RESULTS: In the WAS treatment, PPI significantly enhanced intestinal permeability in vivo compared to that in VT. Moreover, PPI significantly increased paracellular permeability and decreased TEER in the duodenum and jejunum, respectively, compared to those in VT under stressed conditions. Moreover, both vasoactive intestinal peptide (VIP) receptor antagonist and ketotifen significantly reversed the effect of PPI on intestinal permeability. Furthermore, PPI-treated FMT significantly increased the intestinal permeability in vivo compared to that in vehicle-treated FMT. Proton pump inhibitors treatment altered the gut microbiota composition, indicating that PPI induced dysbiosis.<br><br>CONCLUSIONS AND INFERENCES: Under stressed conditions, PPI enhances intestinal permeability via dysbiosis of gut microbiota. Vasoactive intestinal peptide and mast cells are also implicated in the underlying mechanisms.}, }
@article {pmid32318580, year = {2020}, author = {Gerussi, A and Lucà, M and Cristoferi, L and Ronca, V and Mancuso, C and Milani, C and D'Amato, D and O'Donnell, SE and Carbone, M and Invernizzi, P}, title = {New Therapeutic Targets in Autoimmune Cholangiopathies.}, journal = {Frontiers in medicine}, volume = {7}, number = {}, pages = {117}, pmid = {32318580}, issn = {2296-858X}, abstract = {Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholangiopathies characterized by limited treatment options. A more accurate understanding of the several pathways involved in these diseases has fostered the development of novel and promising targeted drugs. For PBC, the characterization of the role of farnesoid X receptor (FXR) and perixosome-proliferator activated receptor (PPAR) has paved the way to several clinical trials including different molecules with choleretic and antinflammatory action. Conversely, different pathogenetic models have been proposed in PSC such as the "leaky gut" hypothesis, a dysbiotic microbiota or a defect in mechanisms protecting against bile acid toxicity. Along these theories, new treatment approaches have been developed, ranging from drugs interfering with trafficking of lymphocytes from the gut to the liver, fecal microbiota transplantation or new biliary acids with possible immunomodulatory potential. Finally, for both diseases, antifibrotic agents are under investigation. In this review, we will illustrate current understanding of molecular mechanisms in PBC and PSC, focusing on actionable biological pathways for which novel treatments are being developed.}, }
@article {pmid32318067, year = {2020}, author = {Zhou, B and Yuan, Y and Zhang, S and Guo, C and Li, X and Li, G and Xiong, W and Zeng, Z}, title = {Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {575}, pmid = {32318067}, issn = {1664-3224}, mesh = {Animals ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunity, Mucosal/*immunology ; Intestinal Mucosa/*immunology/*microbiology ; }, abstract = {The intestinal tract is the largest digestive organ in the human body. It is colonized by, and consistently exposed to, a myriad of microorganisms, including bifidobacteria, lactobacillus, Escherichia coli, enterococcus, clostridium perfringens, and pseudomonas. To protect the body from potential pathogens, the intestinal tract has evolved regional immune characteristics. These characteristics are defined by its unique structure, function, and microenvironment, which differ drastically from those of the common central and peripheral immune organs. The intestinal microenvironment created by the intestinal flora and its products significantly affects the immune function of the region. In turn, specific diseases regulate and influence the composition of the intestinal flora. A constant interplay occurs between the intestinal flora and immune system. Further, the intestinal microenvironment can be reconstructed by probiotic use or microbiota transplantation, functioning to recalibrate the immune homeostasis, while also contributing to the treatment or amelioration of diseases. In this review, we summarize the relationship between the intestinal flora and the occurrence and development of diseases as an in-turn effect on intestinal immunity. We also discuss improved immune function as it relates to non-specific and specific immunity. Further, we discuss the proliferation, differentiation and secretion of immune cells, within the intestinal region following remodeling of the microenvironment as a means to ameliorate and treat diseases. Finally, we suggest strategies for improved utilization of intestinal flora.}, }
@article {pmid32317112, year = {2020}, author = {Gryp, T and De Paepe, K and Vanholder, R and Kerckhof, FM and Van Biesen, W and Van de Wiele, T and Verbeke, F and Speeckaert, M and Joossens, M and Couttenye, MM and Vaneechoutte, M and Glorieux, G}, title = {Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease.}, journal = {Kidney international}, volume = {97}, number = {6}, pages = {1230-1242}, doi = {10.1016/j.kint.2020.01.028}, pmid = {32317112}, issn = {1523-1755}, mesh = {Feces ; *Gastrointestinal Microbiome ; Humans ; Indican ; *Renal Insufficiency, Chronic/diagnosis ; *Toxins, Biological ; *Uremia ; }, abstract = {Chronic kidney disease (CKD) is characterized by accumulation of protein-bound uremic toxins such as p-cresyl sulfate, p-cresyl glucuronide, indoxyl sulfate and indole-3-acetic acid, which originate in the gut. Intestinal bacteria metabolize aromatic amino acids into p-cresol and indole, (further conjugated in the colon mucosa and liver) and indole-3-acetic acid. Here we measured fecal, plasma and urine metabolite concentrations; the contribution of gut bacterial generation to plasma protein-bound uremic toxins accumulation; and influx into the gut of circulating protein-bound uremic toxins at different stages of CKD. Feces, blood and urine were collected from 14 control individuals and 141 patients with CKD. Solutes were quantified by ultra-high performance liquid chromatography. To assess the rate of bacterial generation of p-cresol, indole and indole-3-acetic acid, fecal samples were cultured ex vivo. With CKD progression, an increase in protein-bound uremic toxins levels was observed in plasma, whereas the levels of these toxins and their precursors remained the same in feces and urine. Anaerobic culture of fecal samples showed no difference in ex vivo p-cresol, indole and indole-3-acetic acid generation. Therefore, differences in plasma protein-bound uremic toxins levels between different CKD stages cannot be explained by differences in bacterial generation rates in the gut, suggesting retention due to impaired kidney function as the main contributor to their increased plasma levels. Thus, as fractional clearance decreased with the progression of CKD, tubular clearance appeared to be more affected than the glomerular filtration rate, and there was no net increase in protein-bound uremic toxins influx into the gut lumen with increased plasma levels.}, }
@article {pmid32316741, year = {2021}, author = {Li, J and Yang, X and Zhou, X and Cai, J}, title = {The Role and Mechanism of Intestinal Flora in Blood Pressure Regulation and Hypertension Development.}, journal = {Antioxidants &amp; redox signaling}, volume = {34}, number = {10}, pages = {811-830}, doi = {10.1089/ars.2020.8104}, pmid = {32316741}, issn = {1557-7716}, mesh = {Animals ; Bacteria/drug effects/pathogenicity ; Bacteriophages/genetics ; Blood Pressure/*drug effects ; Dysbiosis/*diet therapy/genetics/microbiology/pathology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/drug effects ; Humans ; Hypertension/*diet therapy/genetics/microbiology/pathology ; Inflammation/*diet therapy/genetics/microbiology/pathology ; }, abstract = {Significance: Hypertension (HTN) has a complex etiology that is characterized by genetic and environmental factors. It has become a global health burden leading to cardiovascular diseases and kidney diseases, ultimately progressing to premature death. Accumulating evidence indicated that gut microbiome was associated with metabolic disorders and inflammation, which were closely linked to HTN. Recent Advances: Recent studies using bacterial genomic analysis and fecal microbiota transplantation as well as many lines of seminal evidence demonstrated that aberrant gut microbiome was significantly associated with HTN. The intestinal microbiome of both patients and animals with HTN had decreased bacterial diversity, disordered microbial structure and functions, and altered end products of fermentation. Gut dysbiosis and metabolites of the gut microbiota play an important role in blood pressure (BP) control, and they are therefore responsible for developing HTN. Critical Issues: This study aimed at focusing on the recent advances in understanding the role played by gut bacteria and the mechanisms underlying the pathological milieu that induced elevated BP and led to HTN pathogenesis. Potential intervention strategies targeting the correction of gut dysbiosis to improve HTN development were summarized. Future Directions: Larger numbers of fecal transplants from participants with HTN should be carried out to examine the magnitude of BP changes with the replacement of the gut microbiome. The proposed mechanisms for the gut in regulating BP remain to be verified. Whether intervention strategies using probiotics, dietary interventions, bacteriophages, and fecal transplants are feasible for individuals with HTN remains to be explored. Antioxid. Redox Signal. 34, 811-830.}, }
@article {pmid32316346, year = {2020}, author = {Gnocchi, M and Gagliardi, M and Gismondi, P and Gaiani, F and De' Angelis, GL and Esposito, S}, title = {Updated Management Guidelines for Clostridioides difficile in Paediatrics.}, journal = {Pathogens (Basel, Switzerland)}, volume = {9}, number = {4}, pages = {}, pmid = {32316346}, issn = {2076-0817}, abstract = {Clostridioides difficile, formerly known as Clostridium difficile, causes infections (CDI) varying from self-limited diarrhoea to severe conditions, including toxic megacolon and bowel perforation. For this reason, a prompt diagnosis is fundamental to early treatment and the prevention of transmission. The aim of this article is to review diagnostic laboratory methods that are now available to detect C. difficile and to discuss the most recent recommendations on CDI treatment in children. Currently, there is no consensus on the best method for detecting C. difficile. Indeed, none of the available diagnostics possess at the same time high sensitivity and specificity, low cost and rapid turnaround times. Appropriate therapy is targeted according to age, severity and recurrence of the episode of infection, and the recent availability of new antibiotics opens new opportunities. De-escalation of antibiotics that are directly associated with CDI remains a priority and the cautious use of probiotics is recommended. Vancomycin represents the first-line therapy for CDI, although in children metronidazole can still be used as a first-line drug. Fidaxomicin is a new treatment option with equivalent initial response rates as vancomycin but lower relapse rates of CDI. Faecal microbiota transplantation should be considered for patients with multiple recurrences of CDI. Monoclonal antibodies and vaccines seem to represent a future perspective against CDI. However, only further studies will permit us to understand whether these new approaches could be effective in therapy and prevention of CDI in paediatric populations.}, }
@article {pmid32313261, year = {2020}, author = {Fouladi, F and Glenny, EM and Bulik-Sullivan, EC and Tsilimigras, MCB and Sioda, M and Thomas, SA and Wang, Y and Djukic, Z and Tang, Q and Tarantino, LM and Bulik, CM and Fodor, AA and Carroll, IM}, title = {Sequence variant analysis reveals poor correlations in microbial taxonomic abundance between humans and mice after gnotobiotic transfer.}, journal = {The ISME journal}, volume = {14}, number = {7}, pages = {1809-1820}, pmid = {32313261}, issn = {1751-7370}, support = {R01 MH105684/MH/NIMH NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; T32 HL129982/HL/NHLBI NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Mice ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Transplanting human gut microbiotas into germ-free (GF) mice is a popular approach to disentangle cause-and-effect relationships between enteric microbes and disease. Algorithm development has enabled sequence variant (SV) identification from 16S rRNA gene sequence data. SV analyses can identify which donor taxa colonize recipient GF mice, and how SV abundance in humans is replicated in these mice. Fecal microbiotas from 8 human subjects were used to generate 77 slurries, which were transplanted into 153 GF mice. Strong correlations between fecal and slurry microbial communities were observed; however, only 42.15 ± 9.95% of SVs successfully transferred from the donor to the corresponding recipient mouse. Firmicutes had a particularly low transfer rate and SV abundance was poorly correlated between donor and recipient pairs. Our study confirms human fecal microbiotas colonize formerly GF mice, but the engrafted community only partially resembles the input human communities. Our findings emphasize the importance of reporting a standardized transfer rate and merit the exploration of other animal models or in silico tools to understand the relationships between human gut microbiotas and disease.}, }
@article {pmid32310042, year = {2020}, author = {De Musis, C and Granata, L and Dallio, M and Miranda, A and Gravina, AG and Romano, M}, title = {Inflammatory Bowel Diseases: The Role of Gut Microbiota.}, journal = {Current pharmaceutical design}, volume = {26}, number = {25}, pages = {2951-2961}, doi = {10.2174/1381612826666200420144128}, pmid = {32310042}, issn = {1873-4286}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases ; *Microbiota ; Prebiotics ; *Probiotics ; }, abstract = {Inflammatory bowel diseases (IBD) are chronic multifactorial diseases characterized by partially unclear pathogenic mechanisms including changes in intestinal microbiota. Despite the microbiota, alteration is well established in IBD patients, as reported by 16RNA sequencing analysis, an important goal is to define if it is just a consequence of the disease progression or a trigger factor of the disease itself. To date, gut microbiota composition and gut microbiota-related metabolites seem to affect the host healthy state both by modulating metabolic pathways or acting on the expression of different genes through epigenetic effects. Because of this, it has been suggested that intestinal microbiota might represent a promising therapeutic target for IBD patients. The aim of this review is to summarize both the most recent acquisitions in the field of gut microbiota and its involvement in intestinal inflammation together with the available strategies for the modulation of microbiota, such as prebiotics and/or probiotics administration or fecal microbiota transplantation.}, }
@article {pmid32308741, year = {2020}, author = {Agrawal, G and Clancy, A and Huynh, R and Borody, T}, title = {Profound remission in Crohn's disease requiring no further treatment for 3-23 years: a case series.}, journal = {Gut pathogens}, volume = {12}, number = {}, pages = {16}, pmid = {32308741}, issn = {1757-4749}, abstract = {BACKGROUND: Crohn's disease (CD) is rising in incidence and has a high morbidity and increased mortality. Current treatment use immunosuppressives but efficacy is suboptimal, and relapse is common. It has been shown that there is an imbalance present in the gut microbiome (dysbiosis) in CD with a possible infective aetiology-Mycobacterium avium subsp. paratuberculosis (MAP) being the most proposed. Antibacterial therapy and Faecal Microbiota Transplantation (FMT) are emerging treatments which can result in clinical and endoscopic remission, if employed correctly. The objective of this study was to report on the treatment and clinical outcomes of patients with CD in prolonged remission.<br><br>RESULTS: Ten patients were identified to have achieved prolonged remission for 3-23&#xa0;years (median 8.5&#xa0;years). Of these, 7/10 took targeted Anti-MAP therapy (AMAT) for a median 36&#xa0;months and then ceased AMAT treatment. After stopping AMAT five patients underwent Faecal Microbiota Transplantation (FMT) (average four infusions). In 4/7, AMAT was combined with infliximab (mean of six infusions) that was withdrawn within 6&#xa0;months after fistulae resolution. One patient achieved deep mucosal healing with AMAT alone. Of the 3/10 patients not prescribed AMAT, one had a combination of anti-inflammatory agents and a single antibiotic (metronidazole) followed by FMT. The other two received only FMT for Clostridioides difficile Infection.<br><br>CONCLUSIONS: Prolonged remission has been achieved for 3-23&#xa0;years with individualised treatments, with the majority using AMAT&#x2009;&#xb1;&#x2009;infliximab and FMT. Treatment with antibiotics and/or FMT provides a potential new avenue for treatment of CD. These findings should stimulate thinking, investigations and better therapy against MAP and&#xa0;the dysbiosis of the gut flora, to enable higher rates of prolonged remission.}, }
@article {pmid32307472, year = {2020}, author = {Hu, X and Mu, R and Xu, M and Yuan, X and Jiang, P and Guo, J and Cao, Y and Zhang, N and Fu, Y}, title = {Gut microbiota mediate the protective effects on endometritis induced by Staphylococcus aureus in mice.}, journal = {Food &amp; function}, volume = {11}, number = {4}, pages = {3695-3705}, doi = {10.1039/c9fo02963j}, pmid = {32307472}, issn = {2042-650X}, mesh = {Animals ; Disease Models, Animal ; Endometritis/*prevention &amp; control ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred BALB C ; Specific Pathogen-Free Organisms ; Staphylococcus aureus/*pathogenicity ; }, abstract = {Endometritis, the inflammation of the endometrial lining caused by bacterial pathogens, is associated with reproductive failure. Recent studies have shown that gut microbiota play an important role in infectious diseases. However, the roles of the gut microbiota in endometritis remain unclear. Here, we assessed the effects and mechanisms of the gut microbiota during endometritis induced by Staphylococcus aureus (S. aureus). A mouse gut microbiota-dysbiosis model was established by a mixture of antibiotics (Abx) and subsequently, a model of endometritis was established by the uterine perfusion of S. aureus. Fecal microbiota transplantation (FMT) was performed to evaluate the relationship between gut microbiota and endometritis. The results showed that the mice with gut microbiota-dysbiosis developed uterine inflammation, while this inflammatory response of the uterus was alleviated in mice with FMT to gut microbiota-dysbiosis. In addition, S. aureus-induced endometritis was greater in severity in the mice with gut dysbiosis as compared to the untreated mice. Moreover, these effects were reversed in mice with FMT to the gut microbiota-dysbiosis. GC-MS analysis demonstrated that the levels of short-chain fatty acids (SCFAs) in the feces of mice with gut microbiota-dysbiosis significantly decreased and pretreatment with sodium butyrate or sodium propionate increased the concentrations of butyrate or propionate in both the circulation and uterine tissues, thereby reducing the severity of endometritis induced by S. aureus. In addition, the increased pathogen load in the uteri of the mice with gut microbiota-dysbiosis was associated with a reduction in the phagocytic ability and responsiveness of neutrophils. In conclusion, the gut microbiota offer a protective effect against S. aureus-induced endometritis by regulating the levels of SCFAs and maintaining the phagocytic ability and responsiveness of neutrophils.}, }
@article {pmid32306706, year = {2020}, author = {Mahajan, R and Midha, V and Singh, A and Mehta, V and Gupta, Y and Kaur, K and Sudhakar, R and Singh Pannu, A and Singh, D and Sood, A}, title = {Incidental benefits after fecal microbiota transplant for ulcerative colitis.}, journal = {Intestinal research}, volume = {18}, number = {3}, pages = {337-340}, pmid = {32306706}, issn = {1598-9100}, abstract = {Gut dysbiosis can result in several diseases, including infections (Clostridium difficile infection and infectious gastroenteritis), autoimmune diseases (inflammatory bowel disease, diabetes, and allergic disorders), behavioral disorders and other conditions like metabolic syndrome and functional gastrointestinal disorders. Amongst various therapies targeting gut microbiome, fecal microbiota transplantation (FMT) is becoming a focus in the public media and peer reviewed literature. We have been using FMT for induction of remission in patients with moderate to severe active ulcerative colitis (UC) and also for subsequent maintenance of remission. Four cases reported incidental benefits while being treated with FMT for UC. These included weight loss (n=1), improvement in hair loss (n=1), amelioration of axial arthritis (n=1) and improvement in allergic rhinitis (n=1), thereby suggesting potential clinical applications of FMT in treating extraintestinal diseases associated with gut dysbiosis.}, }
@article {pmid32305646, year = {2020}, author = {Wang, P and Gao, J and Ke, W and Wang, J and Li, D and Liu, R and Jia, Y and Wang, X and Chen, X and Chen, F and Hu, X}, title = {Resveratrol reduces obesity in high-fat diet-fed mice via modulating the composition and metabolic function of the gut microbiota.}, journal = {Free radical biology &amp; medicine}, volume = {156}, number = {}, pages = {83-98}, doi = {10.1016/j.freeradbiomed.2020.04.013}, pmid = {32305646}, issn = {1873-4596}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Obesity/drug therapy/etiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Resveratrol ; }, abstract = {Resveratrol (RSV) is a natural polyphenol with anti-obesity effects. However, the mechanisms of anti-obesity remain unclear due to its low bioavailability. Recent evidence demonstrates that gut microbiota plays a key role in obesity. This spurred us to investigate whether the anti-obesity effects of RSV are related to modulations in the gut microbiota and metabolic functions. Here, RSV significantly improved metabolic phenotype and intestinal oxidative stress in the high-fat diet (HFD)-fed mice. A multi-omics approach was used to systematically profile the microbial signatures at both the phylogenetic and functional levels using 16S rRNA gene sequencing and metagenome. At the phylogenetic level, RSV treatment significantly modulated the gut microbiota composition in HFD-fed mice, characterized with increased Blautia abundance and decreased Desulfovibrio and Lachnospiraceae_NK4A136_group abundance. At the functional level, RSV significantly decreased the enrichment of pathways linked to host metabolic disease and increased the enrichment of pathways involved in the generation of small metabolites. Besides, the fecal microbiota transplantation experiment showed anti-obesity and microbiota-modulating effects similar to those observed in the oral RSV-feeding experiment. Furthermore, metabolomic analysis and antibiotic treatment verified that 4-hydroxyphenylacetic acid (4-HPA) and 3-hydroxyphenylpropionic acid (3-HPP) were the two gut metabolites of RSV, which contribute to improving lipid metabolism in vitro. Moreover, the content of 4-HPA and 3-HPP exhibited strong correlation with the intestinal oxidative state. We concluded that the RSV-mediated alteration of gut microbiota, related gut metabolites and redox state of the intestinal environment contributed to prevention of metabolic syndrome in HFD-fed mice.}, }
@article {pmid32303608, year = {2021}, author = {Zhang, P and Feng, Y and Li, L and Ge, W and Yu, S and Hao, Y and Shen, W and Han, X and Ma, D and Yin, S and Tian, Y and Min, L and Sun, Z and Sun, Q and Zhang, H and Zhao, Y}, title = {Improvement in sperm quality and spermatogenesis following faecal microbiota transplantation from alginate oligosaccharide dosed mice.}, journal = {Gut}, volume = {70}, number = {1}, pages = {222-225}, pmid = {32303608}, issn = {1468-3288}, mesh = {Alginates ; Animals ; *Fecal Microbiota Transplantation ; Male ; Mice ; Oligosaccharides ; *Sperm Count ; Sperm Motility/*physiology ; Spermatogenesis/*physiology ; }, }
@article {pmid32302004, year = {2020}, author = {Lin, PT and Wang, SH and Chi, CC}, title = {Low molecular weight heparin for prevention of microvascular occlusion in digital replantation.}, journal = {The Cochrane database of systematic reviews}, volume = {4}, number = {4}, pages = {CD009894}, pmid = {32302004}, issn = {1469-493X}, support = {/CSO_/Chief Scientist Office/United Kingdom ; //Scottish Government Health Directorates/International ; //Scottish Government, UK./International ; }, mesh = {Adult ; Anticoagulants/adverse effects/*therapeutic use ; Blood Coagulation Disorders/chemically induced ; Female ; Fingers/blood supply/*transplantation ; Heparin/therapeutic use ; Heparin, Low-Molecular-Weight/adverse effects/*therapeutic use ; Humans ; Male ; Microvessels/*surgery ; Peripheral Arterial Disease/epidemiology ; Postoperative Hemorrhage/chemically induced ; Randomized Controlled Trials as Topic ; Replantation/*adverse effects ; Venous Insufficiency/epidemiology ; }, abstract = {BACKGROUND: The success of digital replantation is highly dependent on the patency of the repaired vessels after microvascular anastomosis. Antithrombotic agents are frequently used for preventing vascular occlusion. Low molecular weight heparin (LMWH) has been reported to be as effective as unfractionated heparin (UFH) in peripheral vascular surgery, but with fewer adverse effects. Its benefit in microvascular surgery such as digital replantation is unclear. This is an update of the review first published in 2013.<br><br>OBJECTIVES: To assess if treatment with subcutaneous LMWH improves the salvage rate of the digits in patients with digital replantation after traumatic amputation.<br><br>SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers, to 17 March 2020. The authors searched PubMed, China National Knowledge Infrastructure (CNKI) and Chinese Electronic Periodical Services (CEPS) on 17 March 2020 and sought additional trials from reference lists of relevant publications.<br><br>SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials comparing treatment with LMWH versus any other treatment in participants who received digital replantation following traumatic digital amputation.<br><br>DATA COLLECTION AND ANALYSIS: Two review authors (PL, CC) independently extracted data and assessed the risk of bias of the included trials using Cochrane's 'Risk of bias' tool. Disagreements were resolved by discussion. We assessed the certainty of evidence using the GRADE approach.<br><br>MAIN RESULTS: We included two new randomised trials in this update, bringing the total number of included trials to four. They included a total of 258 participants, with at least 273 digits, from hospitals in China. Three studies compared LMWH versus UFH, and one compared LMWH versus no LMWH. The mean age of participants ranged from 24.5 to 37.6 years. In the studies reporting the sex of participants, there were a total of 145 men and 59 women. The certainty of the evidence was downgraded to low or very low because all studies were at high risk of performance or reporting bias (or both) and there was imprecision in the results due to the small numbers of participants. The three studies comparing LMWH versus UFH reported the success rate of replantation using different units of analysis (participant or digit), so we were unable to combine data from all three studies (one study reported results for both participants and digits). No evidence of a benefit in success of replantation was seen in the LMWH group when compared with UFH, regardless of whether the outcomes were reported by number of participants (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.87 to 1.10; 130 participants, 2 studies; very low-certainty evidence); or by number of digits (RR 0.97, 95% CI 0.90 to 1.04; 200 digits, 2 studies; low-certainty evidence). No studies reported the incidence of compromised microcirculation requiring surgical or non-surgical therapy, or any systemic/other causes of microvascular insufficiency. There was no evidence of a clear difference between the LMWH and UFH groups in occurrence of arterial occlusion (RR 1.08, 95% CI 0.16 to 7.10; 54 participants, 1 study; very low-certainty evidence) or venous occlusion (RR 0.81, 95% CI 0.20 to 3.27; 54 participants, 1 study; very low-certainty evidence). Two studies reported adverse effects. The LMWH and UFH groups showed no evidence of a difference in wound bleeding (RR 0.53, 95% CI 0.23 to 1.23; 130 participants, 2 studies; low-certainty evidence), haematuria (RR 0.43, 95% CI 0.09 to 2.11; 130 participants, 2 studies; very low-certainty evidence), ecchymoses (RR 0.82, 95% CI 0.21 to 3.19; 130 participants, 2 studies; very low-certainty evidence), epistaxis (RR 0.27, 95% CI 0.03 to 2.32; 130 participants, 2 studies; very low-certainty evidence), gingival bleeding (RR 0.18, 95% CI 0.02 to 1.43; 130 participants, 2 studies; very low-certainty evidence), and faecal occult blood (RR 0.27, 95% CI 0.03 to 2.31; 130 participants, 2 studies; very low-certainty evidence). We could not pool data on coagulation abnormalities as varying definitions and tests were used in the three studies. One study compared LMWH versus no LMWH. The success rate of replantation, when analysed by digits, was reported as 91.2% success in the LMWH group and 82.1% in the control group (RR 1.11, 95% CI 0.93 to 1.33; 73 digits, 1 study; very low-certainty evidence). Compromised microcirculation requiring surgical re-exploration, analysed by digits, was 11.8% in the LMWH group and 17.9% in the control group (RR 0.86, 95% CI 0.21 to 3.58; 73 digits, 1 study; very low-certainty evidence). Compromised microcirculation requiring incision occurred in five out of 34 digits (14.7%) in the LMWH group and eight out of 39 digits (20.5%) in the control group (RR 0.72, 95% CI 0.26 to 1.98; 73 digits; very low-certainty evidence). Microvascular insufficiency due to arterial occlusion, analysed by digits, was 11.8% in the LMWH group and 17.9% in the control group (RR 0.66, 95% CI 0.21 to 2.05; 73 digits, 1 study; very low-certainty evidence), and venous occlusion was 14.7% in the LMWH group and 20.5% in the control (RR 0.72, 95% CI 0.26 to 1.98; 73 digits, 1 study; very low-certainty evidence). The study did not report complications or adverse effects.<br><br>AUTHORS' CONCLUSIONS: There is currently low to very low-certainty evidence, based on four RCTs, suggesting no evidence of a benefit from LMWH when compared to UFH on the success rates of replantation or affect microvascular insufficiency due to vessel occlusion (analysed by digit or participant). LMWH had similar success rates of replantation; and the incidence rate of venous and arterial microvascular insufficiency showed no evidence of a difference between groups when LMWH was compared to no LMWH (analysed by digit). Similar rates of complications and adverse effects were seen between UFH and LMWH. There was insufficient evidence to draw conclusions on any effect on coagulation when comparing LMWH to UFH or no LMWH. The certainty of the evidence was downgraded due to performance and reporting bias, as well as imprecision in the results. Further adequately powered studies are warranted to provide high-certainty evidence.}, }
@article {pmid32300746, year = {2020}, author = {McCune, VL and Quraishi, MN and Manzoor, S and Moran, CE and Banavathi, K and Steed, H and Massey, DCO and Trafford, GR and Iqbal, TH and Hawkey, PM}, title = {Results from the first English stool bank using faecal microbiota transplant as a medicinal product for the treatment of Clostridioides difficile infection.}, journal = {EClinicalMedicine}, volume = {20}, number = {}, pages = {100301}, pmid = {32300746}, issn = {2589-5370}, abstract = {BACKGROUND: Faecal Microbiota Transplant (FMT) has improved outcomes for the treatment of Clostridioides difficile infection (CDI) compared to antibiotic therapy. FMT is classified as a medicinal product in the United Kingdom, similar to the USA and Canada, limiting supply via stool banks without appropriate licencing. In the largest UK cohort to date, we describe the clinical outcomes for 124 patients receiving FMT for recurrent or refractory CDI and present a framework to produce FMT as a licenced medicinal product.<br><br>METHODS: Anonymous unrelated healthy donors, screened via health assessment and microbiological testing donated stool. In aerobic conditions FMT aliquots were prepared for immediate use or frozen storage, following a production framework developed to comply with Good Manufacturing Practice. Outcome measures were clinical response to FMT defined as resolution of diarrhoea within seven days and clinical cure defined as response without diarrhoea recurrence at 90 days.<br><br>FINDINGS: Clinical response was 83&#xb7;9% (95% CI 76&#xb7;0%-90&#xb7;0%) after one treatment. Clinical cure was 78&#xb7;2% (95% CI 67&#xb7;4%-89&#xb7;0%) across the cohort. Refractory cases appeared to have a lower initial clinical response rate compared to recurrent cases, however at day 90 there were no differences observed between these groups.<br><br>INTERPRETATION: The methodology developed here enabled successful licencing of FMT by The Medicines and Healthcare products Regulatory Agency as a medicinal product. This has widened the availability of FMT in the National Health Service via a stool bank and can be applied in other centres across the world to improve access to safe and quality assured treatments.}, }
@article {pmid32300219, year = {2020}, author = {Nazmul Huda, M and Winnike, JH and Crowell, JM and O'Connor, A and Bennett, BJ}, title = {Microbial modulation of host body composition and plasma metabolic profile.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {6545}, pmid = {32300219}, issn = {2045-2322}, support = {P30 DK056350/DK/NIDDK NIH HHS/United States ; R01 HL128572/HL/NHLBI NIH HHS/United States ; }, mesh = {Adiposity ; Animals ; Anti-Bacterial Agents/pharmacology ; Biodiversity ; Biomarkers/*blood ; Blood Glucose/metabolism ; *Body Composition/drug effects ; Cholesterol/blood ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/drug effects ; *Metabolomics ; Mice, Inbred C57BL ; Multivariate Analysis ; Phenotype ; Phylogeny ; Principal Component Analysis ; }, abstract = {The gut microbiota is a critical mediator of nutrition and disease risk. Like most complex traits, the microbiome is under genetic regulation and differs between inbred strains of mice. We tested the effect of fecal microbiota transplantation (FMT) on obesity, and plasma glucose. For this study, we collected microbiota from 2 inbred strains of mice which differ in adiposity and glucose tolerance, C57BL/6J and WSB/EiJ. C57BL/6J female mice (n = 18) were first treated with antibiotics for 4 weeks to ablate the microbiota. Following ablation, the mice were transplanted with microbiota from a C57BL/6J or a WSB/EiJ mouse and clinical traits and plasma metabolomic profiles were interrogated at 2- and 4-weeks post-transplantation. Unexpectedly, the mice receiving WSB/EiJ microbiota increased adiposity but decreased plasma glucose. Metabolomic and 16S microbiota profiling indicated broad metabolic changes occurred during and after FMT. Detailed analysis of these interactions demonstrated specific microbiota-host metabolite interactions which may alter disease susceptibility.}, }
@article {pmid32299514, year = {2020}, author = {Tang, W and Chen, D and Yu, B and He, J and Huang, Z and Zheng, P and Mao, X and Luo, Y and Luo, J and Wang, Q and Wang, H and Yu, J}, title = {Capsulized faecal microbiota transplantation ameliorates post-weaning diarrhoea by modulating the gut microbiota in piglets.}, journal = {Veterinary research}, volume = {51}, number = {1}, pages = {55}, pmid = {32299514}, issn = {1297-9716}, support = {31672436//National Natural Science Foundation of China/ ; 31730091//National Natural Science Foundation of China/ ; CARS-35//China Agriculture Research System/ ; }, mesh = {Animals ; Diarrhea/therapy/*veterinary ; Fecal Microbiota Transplantation/*veterinary ; *Gastrointestinal Microbiome ; *Immunity, Innate ; Male ; Sus scrofa/growth &amp; development/microbiology ; Swine ; Swine Diseases/*therapy ; Weaning ; }, abstract = {Early weaning-induced stress causes diarrhoea, thereby reducing the growth performance of piglets. Gut bacterial dysbiosis has emerged as a leading cause of post-weaning diarrhoea. The present study aimed to investigate the effect of capsulized faecal microbiota transplantation (FMT) on the gut bacterial community, immune response and gut barrier function of piglets. Thirty-two weaned barrows were randomly divided into two groups. The recipient group was inoculated orally with capsulized faecal microbiota of healthy Tibetan pigs during the whole period of the trial, while the control group was given an empty capsule. The feed-to-gain ratio, diarrhoea ratio, and histological damage score of recipient piglets were significantly decreased. FMT treatment significantly increased the colon length of piglets. Furthermore, the relative abundances of Firmicutes, Euryarchaeota, Tenericutes, Lactobacillus, and Methanobrevibacter in the colon of recipient piglets were increased, and the relative abundances of Campylobacter and Proteobacteria were significantly decreased compared with those in the control group. CD4[+] lymphocytes and CD4[+]/CD8[+] ratio in the peripheral blood of recipient piglets were significantly increased. FMT treatment increased the IL-4 and IL-10 levels and decreased the TNF-α and INF-γ levels in the colonic tissue of piglets. The recipient piglets' mRNA expression of TLR2, TLR8, NF-κB, and iNOS was significantly regulated. In addition, FMT significantly enhanced the gene expression of ZO-1. Overall, treatment with capsulized FMT ameliorated diarrhoea in piglets, with significant effects on limiting colon inflammatory responses, downregulating the TLR signalling pathway and the gene expression of iNOS, and strengthening intestinal barrier function by modulating the constituents of the gut microbiota.}, }
@article {pmid32298656, year = {2020}, author = {Leonardi, I and Paramsothy, S and Doron, I and Semon, A and Kaakoush, NO and Clemente, JC and Faith, JJ and Borody, TJ and Mitchell, HM and Colombel, JF and Kamm, MA and Iliev, ID}, title = {Fungal Trans-kingdom Dynamics Linked to Responsiveness to Fecal Microbiota Transplantation (FMT) Therapy in Ulcerative Colitis.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {5}, pages = {823-829.e3}, pmid = {32298656}, issn = {1934-6069}, support = {R01 DK113136/DK/NIDDK NIH HHS/United States ; R01 DK121977/DK/NIDDK NIH HHS/United States ; R56 AI137157/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Antibodies, Fungal/blood ; Bacteria/genetics ; Candida ; Colitis, Ulcerative/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; *Fungi/genetics ; Gastrointestinal Microbiome/physiology ; Humans ; Male ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been successfully applied to ulcerative colitis. However, only a subset of patients responds to FMT, and there is a pressing need for biomarkers of responsiveness. Fungi (the mycobiota) represent a highly immunologically reactive component of the gut microbiota. We analyzed samples from a large randomized controlled trial of FMT for ulcerative colitis (UC). High Candida abundance pre-FMT was associated with a clinical response, whereas decreased Candida abundance post-FMT was indicative of ameliorated disease severity. High pre-FMT Candida was associated with increased bacterial diversity post-FMT, and the presence of genera was linked to FMT responsiveness. Although we detected elevated anti-Candida antibodies in placebo recipients, this increase was abrogated in FMT recipients. Our data suggest that FMT might reduce Candida to contain pro-inflammatory immunity during intestinal disease and highlight the utility of mycobiota-focused approaches to identify FMT responders prior to therapy initiation.}, }
@article {pmid32297646, year = {2020}, author = {Kilinçarslan, S and Evrensel, A}, title = {The effect of fecal microbiota transplantation on psychiatric symptoms among patients with inflammatory bowel disease: an experimental study.}, journal = {Actas espanolas de psiquiatria}, volume = {48}, number = {1}, pages = {1-7}, pmid = {32297646}, issn = {1578-2735}, mesh = {Adult ; Anxiety Disorders/*psychology ; Brief Psychiatric Rating Scale/statistics &amp; numerical data ; Depressive Disorder/*psychology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*complications/microbiology/*therapy ; Interviews as Topic ; Male ; Patients/statistics &amp; numerical data ; }, abstract = {INTRODUCTION: Over the past decade, evidence that supports the relationship between intestinal microbiota and the brain has been obtained. Ageing, stress, nutrition and medicines can alter the composition of bacteria in the intestinal microbiota. This condition, called dysbiosis, can be repaired through prebiotics, probiotics or fecal microbiota transplantation (FMT). FMT is effective in the treatment of inflammatory bowel diseases (IBD). Information on FMT's use with psychiatric disorders is limited. This study aims to investigate changes in the severity of depression, anxiety and obsession of patients who received FMT for the treatment of inflammatory bowel diseases.<br><br>METHODS: This study was conducted with 10 patients with IBD who underwent FMT between March and September 2017. FMT was performed by an experienced gastroenterologist. The patients completed the Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R) and Maudsley Obsessive Compulsive Inventory (MOCI) before FMT and again at 1 month after FMT.<br><br>RESULTS: Significant decreases were found in BDI (Z=2.49, p=0.013), SCL-90-R (Z=-2.09, p=0.037) and MOCI (Z=2.08, p=0.037) scores after 1 month of FMT. Although the SCL-90-R anxiety subscale scores decreased, this decrease was not statistically significant (Z=-1.55, p=0.121).<br><br>CONCLUSIONS: The severity of anxiety, depression and obsession in IBD patients decreased after FMT. The decrease in psychiatric symptoms may result from the direct neuropsychiatric effect of FMT (primary effect), but also the improvement of gastrointestinal symptoms (secondary effect). Another possibility is that this result is independent of these two conditions. Therefore, the results of our study are not sufficient to establish a cause-effect relationship. More randomised controlled trials with larger samples from patients with anxiety or depression but without comorbid physical illnesses are needed to generalise these results.}, }
@article {pmid32296975, year = {2020}, author = {Fadda, HM}, title = {The Route to Palatable Fecal Microbiota Transplantation.}, journal = {AAPS PharmSciTech}, volume = {21}, number = {3}, pages = {114}, doi = {10.1208/s12249-020-1637-z}, pmid = {32296975}, issn = {1530-9932}, mesh = {Capsules ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; }, abstract = {The community of symbiotic microorganisms that reside in our gastrointestinal tract is integral to human health. Fecal microbiota transplantation (FMT) has been shown to be highly effective in treating recurrent Clostridioides difficile infection (rCDI) and is now recommended by medical societies for patients suffering from rCDI who have failed to respond to conventional therapy. The main challenges with FMT are its accessibility, acceptability, lack of standardization, and regulatory complexity, which will be discussed in this review. Access to FMT is being addressed through the development of frozen and lyophilized FMT preparations that can be prepared at stool banks and shipped to the point of care. Both access and patient acceptance would be enhanced by oral FMT capsules, and there is potential to reduce capsule burden by utilizing colonic release capsules, targeting the site of disease. This review compares the efficacy of different FMT routes of administration: capsules, nasal feeding tubes, enemas, and colonoscopic infusions. FMT is considered investigational by the Food and Drug Administration. In effort to improve access to FMT, physicians may perform FMT outside of an investigational new drug application for treating CDI infections not responsive to standard therapies. The majority of FMT studies report only minor adverse effects; however, there is risk of transmission of infections.}, }
@article {pmid32296105, year = {2020}, author = {Sanada, S and Suzuki, T and Nagata, A and Hashidume, T and Yoshikawa, Y and Miyoshi, N}, title = {Intestinal microbial metabolite stercobilin involvement in the chronic inflammation of ob/ob mice.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {6479}, pmid = {32296105}, issn = {2045-2322}, mesh = {Animals ; Bile Pigments/*blood/immunology/metabolism ; Biomarkers/blood/metabolism ; Disease Models, Animal ; Gastrointestinal Microbiome/*immunology ; Host Microbial Interactions/*immunology ; Humans ; Inflammation/blood/diagnosis/*immunology/microbiology ; Intestinal Mucosa/immunology/metabolism/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/blood/genetics/*immunology/microbiology ; RAW 264.7 Cells ; }, abstract = {It is crucial that the host and intestinal microflora interact and influence each other to maintain homeostasis and trigger pathological processes. Recent studies have shown that transplantation of the murine intestinal content to recipient germ-free mice enables transmission of the donor's phenotypes, such as low level chronic inflammation associated with lifestyle-related diseases. These findings indicate that intestinal bacteria produce some molecules to trigger pathological signals. However, fecal microbial metabolites that induce obesity and the type II diabetic phenotype have not been fully clarified. Here, we showed that the intestinal bacterial metabolite stercobilin, a pigment of feces, induced proinflammatory activities including TNF-α and IL-1β induction in mouse macrophage RAW264 cells. Proinflammatory stercobilin levels were significantly higher in ob/ob mice feces than in the feces of control C57BL/6 J mice. Moreover, in this study, we detected stercobilin in mice plasma for the first time, and the levels were higher in ob/ob mice than that of C57BL/6 J mice. Therefore, stercobilin is potentially reabsorbed, circulated through the blood system, and contributes to low level chronic inflammation in ob/ob mice. Since, stercobilin is a bioactive metabolite, it could be a potentially promising biomarker for diagnosis. Further analyses to elucidate the metabolic rate and the reabsorption mechanism of stercobilin may provide possible therapeutic and preventive targets.}, }
@article {pmid32295752, year = {2021}, author = {Minichino, A and Brondino, N and Solmi, M and Del Giovane, C and Fusar-Poli, P and Burnet, P and Cipriani, A and Lennox, BR}, title = {The gut-microbiome as a target for the treatment of schizophrenia: A systematic review and meta-analysis of randomised controlled trials of add-on strategies.}, journal = {Schizophrenia research}, volume = {234}, number = {}, pages = {1-13}, doi = {10.1016/j.schres.2020.02.012}, pmid = {32295752}, issn = {1573-2509}, support = {MR/J012939/1/MRC_/Medical Research Council/United Kingdom ; RP-2017-08-ST2-006/DH_/Department of Health/United Kingdom ; BRC-1215-20005/DH_/Department of Health/United Kingdom ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; *Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; *Psychotic Disorders/drug therapy ; Randomized Controlled Trials as Topic ; *Schizophrenia/drug therapy ; }, abstract = {The gut-microbiome has been hypothesised as a novel potential target for intervention for schizophrenia. We tested this hypothesis with a systematic review and meta-analysis of studies investigating the efficacy and acceptability of add-on strategies known to affect the gut-microbiome for the treatment of schizophrenia. Following PRISMA guidelines, we searched from inception to August 2019 all the randomised double-blind controlled trials of add-on antibiotics, antimicrobials, pre/probiotics, and faecal transplant in schizophrenia. Primary outcomes were severity of negative symptoms and acceptability of treatment. Data were independently extracted by multiple observers and a random-mixed model was used for the analysis. Heterogeneity was assessed with the I[2] index. We identified 28 eligible trials: 21 investigated antibiotics, 4 antimicrobials (Artemisinin, Artemether, and Sodium Benzoate), 3 pre/probiotics, none faecal transplant. Results showed no effect of D-Cycloserine (10 studies; SMD, -0.16; 95% CI -0.40, 0.08; P = .20; I[2]: 28.2%), Minocycline (7 studies; SMD: -0.35; 95% CI -0.70, 0.00; P = .05, I[2]:77.7%), other antibiotics (2 studies), probiotics alone (1 study), and Artemisinin (1 study) on negative symptoms of schizophrenia when compared to placebo. Limited evidence suggests efficacy on negative symptoms for Sodium benzoate (2 studies; SMD, -0.63; 95%CI -1.03, -0.23; P < .001; I[2]:0%), Artemether (1 study), and probiotics combined with Vitamin D (1 study) when compared to placebo. Acceptability of intervention was similar to placebo. Negative findings were mainly led by antibiotics trials, with paucity of evidence available on pre/probiotics. There is a need of expanding our knowledge on the clinical relevance of gut-microbiome-host interaction in psychosis before engaging in further trials.}, }
@article {pmid32291810, year = {2020}, author = {Gallo, A and Cancelli, C and Ceron, E and Covino, M and Capoluongo, E and Pocino, K and Ianiro, G and Cammarota, G and Gasbarrini, A and Montalto, M}, title = {Fecal calprotectin and need of multiple microbiota trasplantation infusions in Clostridium difficile infection.}, journal = {Journal of gastroenterology and hepatology}, volume = {35}, number = {11}, pages = {1909-1915}, doi = {10.1111/jgh.15072}, pmid = {32291810}, issn = {1440-1746}, mesh = {Aged ; Aged, 80 and over ; Biomarkers/analysis ; *Clostridioides difficile ; *Clostridium Infections ; Colitis/diagnosis/*microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*chemistry ; Female ; Humans ; Leukocyte L1 Antigen Complex/*analysis ; Male ; Recurrence ; Retreatment ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) has proven to be very effective in recurrent Clostridium difficile infection (CDI) when compared with standard antibiotic therapy. However, given the lack of validated criteria, decision regarding number and timing of infusions is currently based on the clinician's experience, severity of infection, and clinical response. We performed a longitudinal assessment of fecal calprotectin concentration (FCC) in CDI patients undergoing FMT. FCCs were correlated with the need for multiple infusions and with the clinical status of the patient.<br><br>METHODS: Fecal calprotectin concentration measurement was performed just before first procedure (T0) and 2 (T1) and 5 (T2) days later. The need for reinfusion was accounted for in the 8&#xa0;weeks following procedure, and clinical status was evaluated at the end of the given period. Both outcomes were correlated with measured FCCs.<br><br>RESULTS: A total of 28 CDI patients undergoing FMT were enrolled. Median FCCs at T0 were significantly higher in patients who needed repeat FMT, 540&#xa0;&#x3bc;g/g versus patients who underwent single FMT, 290&#xa0;&#x3bc;g/g (P&#xa0;<&#xa0;0.05). Differences were not significant for FCC at T1 and T2 . Regarding correlation with clinical outcome, median FCC at T0 was found to be lower in responders compared with non-responders with a trend towards statistical significance (P&#xa0;=&#xa0;0.07). Correlation at T1 and T2 was not significant.<br><br>CONCLUSIONS: The use of an easily obtainable parameter such as fecal calprotectin could possibly optimize overall management of FMT procedural framework potentially being able to immediately identify patients who may benefit from repeat infusions.}, }
@article {pmid32289500, year = {2020}, author = {Esquerre, N and Basso, L and Defaye, M and Vicentini, FA and Cluny, N and Bihan, D and Hirota, SA and Schick, A and Jijon, HB and Lewis, IA and Geuking, MB and Sharkey, KA and Altier, C and Nasser, Y}, title = {Colitis-Induced Microbial Perturbation Promotes Postinflammatory Visceral Hypersensitivity.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {10}, number = {2}, pages = {225-244}, pmid = {32289500}, issn = {2352-345X}, support = {//CIHR/Canada ; }, mesh = {Animals ; Colitis, Ulcerative/chemically induced/*complications/immunology/microbiology ; Colon/drug effects/immunology/microbiology/pathology ; Dextran Sulfate/administration &amp; dosage/toxicity ; Disease Models, Animal ; Dysbiosis/*immunology/microbiology ; Fatty Acids, Volatile/analysis/metabolism ; Feces/chemistry/microbiology ; Gastrointestinal Microbiome/*immunology ; Humans ; Intestinal Mucosa/drug effects/immunology/microbiology/pathology ; Male ; Mice ; Nociception ; Nociceptors/immunology/metabolism ; TRPV Cation Channels/metabolism ; Visceral Pain/*immunology/microbiology ; }, abstract = {BACKGROUND &amp; AIMS: Despite achieving endoscopic remission, more than 20% of inflammatory bowel disease patients experience chronic abdominal pain. These patients have increased rectal transient receptor potential vanilloid-1 receptor (TRPV1) expression, a key transducer of inflammatory pain. Because inflammatory bowel disease patients in remission exhibit dysbiosis and microbial manipulation alters TRPV1 function, our goal was to examine whether microbial perturbation modulated transient receptor potential function in a mouse model.<br><br>METHODS: Mice were given dextran sodium sulfate (DSS) to induce colitis and were allowed to recover. The microbiome was perturbed by using antibiotics as well as fecal microbial transplant (FMT). Visceral and somatic sensitivity were assessed by recording visceromotor responses to colorectal distention and using hot plate/automated Von Frey tests, respectively. Calcium imaging of isolated dorsal root ganglia neurons was used as an in&#xa0;vitro correlate of nociception. The microbiome composition was evaluated via 16S rRNA gene variable region V4 amplicon sequencing, whereas fecal short-chain fatty acids (SCFAs) were assessed by using targeted mass spectrometry.<br><br>RESULTS: Postinflammatory DSS mice developed visceral and somatic hyperalgesia. Antibiotic administration during DSS recovery induced visceral, but not somatic, hyperalgesia independent of inflammation. FMT of postinflammatory DSS stool into antibiotic-treated mice increased visceral hypersensitivity, whereas FMT of control stool reversed antibiotics' sensitizing effects. Postinflammatory mice exhibited both increased SCFA-producing species and fecal acetate/butyrate content compared with controls. Capsaicin-evoked calcium responses were increased in naive dorsal root ganglion neurons incubated with both sodium butyrate/propionate alone and with colonic supernatants derived from postinflammatory mice.<br><br>CONCLUSIONS: The microbiome plays a central role in postinflammatory visceral hypersensitivity. Microbial-derived SCFAs can sensitize nociceptive neurons and may contribute to the pathogenesis of postinflammatory visceral pain.}, }
@article {pmid32289499, year = {2020}, author = {Moltzau Anderson, J and Lipinski, S and Sommer, F and Pan, WH and Boulard, O and Rehman, A and Falk-Paulsen, M and Stengel, ST and Aden, K and Häsler, R and Bharti, R and Künzel, S and Baines, JF and Chamaillard, M and Rosenstiel, P}, title = {NOD2 Influences Trajectories of Intestinal Microbiota Recovery After Antibiotic Perturbation.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {10}, number = {2}, pages = {365-389}, pmid = {32289499}, issn = {2352-345X}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Crohn Disease/*genetics/immunology/microbiology ; DNA, Bacterial/isolation &amp; purification ; DNA, Fungal/isolation &amp; purification ; Disease Models, Animal ; Dysbiosis/*chemically induced/genetics/immunology/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects/*immunology ; Germ-Free Life ; Humans ; Intestinal Mucosa/immunology/microbiology ; Loss of Function Mutation ; Mice ; Mice, Knockout ; Nod2 Signaling Adaptor Protein/*deficiency/genetics ; RNA, Ribosomal, 16S/genetics ; Signal Transduction/immunology ; }, abstract = {BACKGROUND &amp; AIMS: Loss-of-function variants in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) impair the recognition of the bacterial cell wall component muramyl-dipeptide and are associated with an increased risk for developing Crohn's disease. Likewise, exposure to antibiotics increases the individual risk for developing inflammatory bowel disease. Here, we studied the long-term impact of NOD2 on the ability of the gut bacterial and fungal microbiota to recover after antibiotic treatment.<br><br>METHODS: Two cohorts of 20-week-old and 52-week-old wild-type (WT) C57BL/6J and NOD2 knockout (Nod2-KO) mice were treated with broad-spectrum antibiotics and fecal samples were collected to investigate temporal dynamics of the intestinal microbiota (bacteria and fungi) using 16S ribosomal RNA and internal transcribed spacer 1 sequencing. In addition, 2 sets of germ-free WT mice were colonized with either WT or Nod2-KO after antibiotic donor microbiota and the severity of intestinal inflammation was monitored in the colonized mice.<br><br>RESULTS: Antibiotic exposure caused long-term shifts in the bacterial and fungal community composition. Genetic ablation of NOD2 was associated with delayed body weight gain after antibiotic treatment and an impaired recovery of the bacterial gut microbiota. Transfer of the postantibiotic fecal microbiota of Nod2-KO mice induced an intestinal inflammatory response in the colons of germ-free recipient mice compared with respective microbiota from WT controls based on histopathology and gene expression analyses.<br><br>CONCLUSIONS: Our data show that the bacterial sensor NOD2 contributes to intestinal microbial community composition after antibiotic treatment and may add to the explanation of how defects in the NOD2 signaling pathway are involved in the etiology of Crohn's disease.}, }
@article {pmid32285709, year = {2020}, author = {Kousgaard, SJ and Michaelsen, TY and Nielsen, HL and Kirk, KF and Brandt, J and Albertsen, M and Thorlacius-Ussing, O}, title = {Clinical results and microbiota changes after faecal microbiota transplantation for chronic pouchitis: a pilot study.}, journal = {Scandinavian journal of gastroenterology}, volume = {55}, number = {4}, pages = {421-429}, doi = {10.1080/00365521.2020.1748221}, pmid = {32285709}, issn = {1502-7708}, mesh = {Adult ; Chronic Disease ; Denmark ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Pilot Projects ; Pouchitis/microbiology/*therapy ; Prospective Studies ; Remission Induction ; }, abstract = {Objectives: Research evidence suggests that chronic pouchitis is associated with intestinal dysbiosis. Faecal microbiota transplantation (FMT) has been proposed as a possible treatment. We performed a 6-month prospective, open-label, single-centre cohort pilot-study (NCT03538366) to investigate if FMT could improve clinical outcome and alter gut microbiota in patients with chronic pouchitis.Materials and methods: Nine adult patients with chronic pouchitis were included and allocated to 14 days FMT by enemas from five faecal donors, with a 6-month follow-up. Pouchitis severity was assessed using pouchitis disease activity index (PDAI) before and after FMT. Changes in gut microbiota, and engraftment of donor's microbiota were assessed in faecal samples.Results: All patients were treated with FMT for 14 continuous days. Overall, four of nine patients receiving FMT were in clinical remission at 30-day follow-up, and three patients remained in remission until 6-month follow-up. Clinical symptoms of pouchitis improved significantly between inclusion and 14-day follow-up (p = .02), but there was no improvement in PDAI between inclusion (mean 8.6) and 30-day follow-up (mean 5.2). Treatment with FMT caused a substantial shift in microbiota and increased microbial diversity in six patients, resembling that of the donors, with a high engraftment of specific donor microbiota.Conclusions: Symptomatic benefit in FMT treatment was found for four of nine patients with chronic pouchitis with increased microbial diversity and high engraftment of donor's microbiota. A larger, randomised controlled study is required to fully evaluate the potential role of FMT in treating chronic pouchitis.}, }
@article {pmid32282545, year = {2020}, author = {Li, Q and Zhang, T and Ding, X and Xiang, L and Cui, B and Buch, H and Zhang, F}, title = {Enhancing patient adherence to fecal microbiota transplantation maintains the long-term clinical effects in ulcerative colitis.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {32}, number = {8}, pages = {955-962}, pmid = {32282545}, issn = {1473-5687}, mesh = {*Colitis, Ulcerative/diagnosis/therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; Patient Compliance ; Reproducibility of Results ; Treatment Outcome ; }, abstract = {OBJECTIVES: The way to improve the long-term efficacy of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study mainly dedicated to the UC patients' satisfaction with FMT and the importance of patients' adherence to repeated FMT for long-term clinical outcomes.<br><br>METHODS: Patients with UC who underwent FMT at our center from November 2012 to September 2018 were included. We assessed patient satisfaction with efficacy, safety, and reliability of FMT, as well as adherence to the repeated FMT.<br><br>RESULTS: One hundred and seventy-six patients were included in the analysis. The median follow-up duration of the study was 25.5 (interquartile range 13.0-46.5) months. The clinical response rate at 1 week, 1 month, 3 months, and 6 months after FMT was 48.9%, 69.3%, 49.4%, and 32.7%, respectively. 3.4% (6/176) of patients underwent colectomy after FMT during our long-term follow-up. Partial Mayo score at 1-month post-FMT (P < 0.001) was an independent factor of patients' satisfaction. The laboratory preparation process was related to the incidence of adverse events (P < 0.05). 23.8% (29/122) of patients with a good adherence followed our recommendation to undergo the second course of FMT and achieved a longer clinical response compared with the patients with poor adherence (P < 0.001).<br><br>CONCLUSION: Patients' good adherence to repeated FMT is important to maintain long-term clinical benefits achieved from FMT in UC. Registration number: NCT01790061.}, }
@article {pmid32280227, year = {2020}, author = {Liu, S and Guo, R and Liu, F and Yuan, Q and Yu, Y and Ren, F}, title = {Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial Pathway.}, journal = {Neuropsychiatric disease and treatment}, volume = {16}, number = {}, pages = {859-869}, pmid = {32280227}, issn = {1176-6328}, abstract = {PURPOSE: Gut microbiota affects various physiological functions in the host and has crucial effects on the nervous system. There is increasing evidence of a correlation between gut microbiota and depression; however, the mechanisms underlying the regulation of depression-like behavior by gut microbiota remain unclear. In this study, we assessed the regulatory mechanism of gut microbiota on depression-like behavior in rats.<br><br>METHODS: We transplanted fecal microbiota obtained from patients with depression and healthy individuals into germ-free (GF) rats (n=18) through fecal microbiota transplantation technology. Next, we assessed the affective behavior in the rats using the forced swimming test and a sucrose preference test. We used enzyme-linked immunosorbent assay (ELISA) to determine the hippocampal levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and noradrenaline (NE) and the serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), interferon-&#x3b3; (IFN-&#x3b3;), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-1 (IL-4), and interleukin-1 (IL-10). The mitochondrial morphology of small intestinal epithelial cells was observed through transmission electron microscopy.<br><br>RESULTS: Rats that received fecal microbiota from patients with depression (depression microbiota) exhibited depression-like behavior. They presented decreased levels of hippocampal neurotransmitters, serum CORT levels, and anti-inflammatory cytokine levels, as well as increased ACTH, CRH, and serum levels of multiple pro-inflammatory cytokines. Observation of the mitochondria ultrastructure showed damaged mitochondria in the intestinal epithelial cells, significant endoplasmic reticulum expansion, and border aggregation of nuclear chromatin.<br><br>CONCLUSION: Our findings suggested that the depression-like behaviors induced by the depression microbiota through the neuroendocrine-immune-mitochondrial pathway, which were associated with neuroendocrine disorders, inflammatory responses, and mitochondrial damage.}, }
@article {pmid32279172, year = {2021}, author = {Chauhan, A and Kumar, R and Sharma, S and Mahanta, M and Vayuuru, SK and Nayak, B and Kumar, S and Shalimar, }, title = {Fecal Microbiota Transplantation in Hepatitis B e Antigen-Positive Chronic Hepatitis B Patients: A Pilot Study.}, journal = {Digestive diseases and sciences}, volume = {66}, number = {3}, pages = {873-880}, pmid = {32279172}, issn = {1573-2568}, mesh = {Adult ; Antiviral Agents/therapeutic use ; DNA, Viral/blood/immunology ; Fecal Microbiota Transplantation/*methods ; Female ; Hepatitis B Surface Antigens/blood/immunology ; Hepatitis B e Antigens/*blood/immunology ; Hepatitis B virus/*immunology ; Hepatitis B, Chronic/blood/*therapy/virology ; Humans ; Male ; Pilot Projects ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Intestinal flora plays a critical role in immunity against hepatitis B virus (HBV). Fecal Microbiota Transplantation (FMT) may be a potential immunomodulatory therapy in patients with chronic hepatitis B (CHB).<br><br>AIM: We aimed to study role of FMT in hepatitis B e antigen (HBeAg)-positive CHB patients in terms of its effect on HBeAg, HBsAg, and HBV DNA.<br><br>METHODS: HBeAg-positive patients despite being on antiviral treatment for&#x2009;>&#x2009;1&#xa0;year were given six cycles of FMT via gastroscope (nasoduodenal route) at 4 weekly intervals along with antiviral therapy. Twelve out of 14 included patients in FMT arm completed six cycles. Another 15 HBeAg-positive patients who were on oral antivirals for&#x2009;>&#x2009;1&#xa0;year were taken as control-antiviral therapy (AVT) arm. Per-protocol analysis was done.<br><br>RESULTS: The median (interquartile range) age in the FMT and AVT arm were 29 (25-35) and 29(24-38), respectively (P&#x2009;=&#x2009;0.794). The median (interquartile range) duration of AVT prior to inclusion in the study was 80 (52-104) and 76 (52-114) months in FMT and AVT arm, respectively (P&#x2009;=&#x2009;0.884). In the FMT arm, 16.7% (2/12) patients had HBeAg clearance in comparison to none in the AVT arm (P&#x2009;=&#x2009;0.188). None of the patients in either arm had HBsAg loss. The FMT was tolerated well, 42.8% (6/14) patients reported one or more minor adverse events.<br><br>CONCLUSIONS: In this non-randomized pilot study, FMT appears to be safe and potentially effective in terms of viral suppression and HBeAg clearance in patients with HBeAg-positive CHB. Further randomized controlled trials are needed in order to obtain robust conclusions.}, }
@article {pmid32278875, year = {2020}, author = {Ricciuto, A and Sherman, PM and Laxer, RM}, title = {Gut microbiota in chronic inflammatory disorders: A focus on pediatric inflammatory bowel diseases and juvenile idiopathic arthritis.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {215}, number = {}, pages = {108415}, doi = {10.1016/j.clim.2020.108415}, pmid = {32278875}, issn = {1521-7035}, mesh = {Adaptive Immunity/immunology ; Animals ; Arthritis, Juvenile/*immunology/*microbiology ; Chronic Disease ; Gastrointestinal Microbiome/*immunology ; Humans ; Immune System/immunology ; Immunity, Innate/immunology ; Inflammatory Bowel Diseases/*immunology/*microbiology ; }, abstract = {The gut microbiota is integral to human health, including maintaining the delicate balance between tolerance and protection against potentially harmful pathogens. A growing body of evidence implicates the intestinal microbiome in immune-mediated inflammatory disorders; these data span the spectrum from genetic and environmental disease risk factors, to animal studies (particularly germ-free and gnotobiotic models) and human studies, including evidence of dysbiosis in diseased individuals compared to healthy populations. In this review, we summarize both animal and human data supporting a link between the gut microbiota and inflammatory bowel diseases (IBD) and systemic inflammatory arthritis, as models for chronic inflammatory disorders, while offering a pediatric focus (pediatric IBD and juvenile idiopathic arthritis). We discuss relevant mechanisms related to the crosstalk between the gut microbiota and the innate and adaptive immune system. We close with a brief discussion of emerging microbe-altering interventions, including fecal microbial transplantation and its immunologic effects.}, }
@article {pmid32278666, year = {2019}, author = {Kodati, S and Sen, HN}, title = {Uveitis and the gut microbiota.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {33}, number = {6}, pages = {101500}, pmid = {32278666}, issn = {1532-1770}, support = {ZIA EY000556/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Autoimmunity ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Mice ; *Microbiota ; *Uveitis/microbiology ; }, abstract = {Uveitis is a heterogeneous collection of inflammatory diseases of the intraocular uveal tissues and adjacent structures, and they collectively are a significant cause of visual morbidity. In recent years, investigating the contribution of the gut microbiota to autoimmunity, including the development of uveitis, has gained interest. Decreased disease severity has been observed in both the induced experimental autoimmune model of uveitis and the spontaneous RI61H model of uveitis in mice treated with oral broad-spectrum antibiotics and raised in germ-free conditions, implicating a role for the gut microbiota in the development of disease in these models. Also, in support of these findings are the differences in the composition of the microbiota that have been reported in uveitis patients. Proposed mechanisms accounting for the microbiota triggering uveitis include antigenic mimicry and dysbiosis leading to dysregulation of the immune system. An improved understanding of these mechanisms will facilitate potential therapeutic approaches including alteration of the microbiota with probiotic treatment and fecal microbiota transplants.}, }
@article {pmid32277897, year = {2020}, author = {Kelly, CR and Kahn, SA}, title = {Is it unethical to conduct placebo-controlled trials of faecal microbiota transplantation for recurrent Clostridioides difficile infection?.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {5}, number = {5}, pages = {432-433}, doi = {10.1016/S2468-1253(20)30043-1}, pmid = {32277897}, issn = {2468-1253}, mesh = {*Clostridioides difficile ; Controlled Clinical Trials as Topic/*ethics ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Placebos/*therapeutic use ; Recurrence ; Therapeutic Equipoise ; }, }
@article {pmid32277534, year = {2020}, author = {Meng, X and Zhang, G and Cao, H and Yu, D and Fang, X and de Vos, WM and Wu, H}, title = {Gut dysbacteriosis and intestinal disease: mechanism and treatment.}, journal = {Journal of applied microbiology}, volume = {129}, number = {4}, pages = {787-805}, pmid = {32277534}, issn = {1365-2672}, support = {17SDG33410868/AHA/American Heart Association-American Stroke Association/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Dysbiosis/*microbiology/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestinal Diseases/*microbiology/therapy ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {The gut microbiome functions like an endocrine organ, generating bioactive metabolites, enzymes or small molecules that can impact host physiology. Gut dysbacteriosis is associated with many intestinal diseases including (but not limited to) inflammatory bowel disease, primary sclerosing cholangitis-IBD, irritable bowel syndrome, chronic constipation, osmotic diarrhoea and colorectal cancer. The potential pathogenic mechanism of gut dysbacteriosis associated with intestinal diseases includes the alteration of composition of gut microbiota as well as the gut microbiota-derived signalling molecules. The many correlations between the latter and the susceptibility for intestinal diseases has placed a spotlight on the gut microbiome as a potential novel target for therapeutics. Currently, faecal microbial transplantation, dietary interventions, use of probiotics, prebiotics and drugs are the major therapeutic tools utilized to impact dysbacteriosis and associated intestinal diseases. In this review, we systematically summarized the role of intestinal microbiome in the occurrence and development of intestinal diseases. The potential mechanism of the complex interplay between gut dysbacteriosis and intestinal diseases, and the treatment methods are also highlighted.}, }
@article {pmid32276499, year = {2020}, author = {Fond, GB and Lagier, JC and Honore, S and Lancon, C and Korchia, T and Sunhary De Verville, PL and Llorca, PM and Auquier, P and Guedj, E and Boyer, L}, title = {Microbiota-Orientated Treatments for Major Depression and Schizophrenia.}, journal = {Nutrients}, volume = {12}, number = {4}, pages = {}, pmid = {32276499}, issn = {2072-6643}, mesh = {Adult ; Biological Therapy/*methods ; Depressive Disorder, Major/*microbiology/*therapy ; Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Microbiota ; Middle Aged ; Probiotics/therapeutic use ; Schizophrenia/*microbiology/*therapy ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND AND SIGNIFICANCE: There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks.<br><br>METHOD: This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia.<br><br>RESULTS: The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics' impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration.<br><br>CONCLUSION: Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials.}, }
@article {pmid32275059, year = {2021}, author = {Revolinski, S and Munoz-Price, LS}, title = {Fecal Microbiota Transplantation for Clostridioides difficile Infection in Immunocompromised Hosts.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {72}, number = {12}, pages = {2247}, doi = {10.1093/cid/ciz689}, pmid = {32275059}, issn = {1537-6591}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Immunocompromised Host ; }, }
@article {pmid32273468, year = {2020}, author = {Bessman, NJ and Mathieu, JRR and Renassia, C and Zhou, L and Fung, TC and Fernandez, KC and Austin, C and Moeller, JB and Zumerle, S and Louis, S and Vaulont, S and Ajami, NJ and Sokol, H and Putzel, GG and Arvedson, T and Sockolow, RE and Lakhal-Littleton, S and Cloonan, SM and Arora, M and Peyssonnaux, C and Sonnenberg, GF}, title = {Dendritic cell-derived hepcidin sequesters iron from the microbiota to promote mucosal healing.}, journal = {Science (New York, N.Y.)}, volume = {368}, number = {6487}, pages = {186-189}, pmid = {32273468}, issn = {1095-9203}, support = {R21 CA249274/CA/NCI NIH HHS/United States ; R01 AI145989/AI/NIAID NIH HHS/United States ; R01 AI123368/AI/NIAID NIH HHS/United States ; R01 DK126871/DK/NIDDK NIH HHS/United States ; P30 ES023515/ES/NIEHS NIH HHS/United States ; F32 AI124517/AI/NIAID NIH HHS/United States ; FS/12/63/29895/BHF_/British Heart Foundation/United Kingdom ; U2C ES030859/ES/NIEHS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; R01 AI143842/AI/NIAID NIH HHS/United States ; U01 AI095608/AI/NIAID NIH HHS/United States ; 261296/ERC_/European Research Council/International ; R01 AI162936/AI/NIAID NIH HHS/United States ; R00 HL125899/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cation Transport Proteins/metabolism ; Dendritic Cells/*metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gene Deletion ; Hepcidins/genetics/*metabolism ; Homeostasis ; Intestinal Diseases/*microbiology ; Intestinal Mucosa/*microbiology/*physiology ; Iron/*metabolism ; Mice ; Mice, Mutant Strains ; Phagocytes/metabolism ; Ferroportin ; }, abstract = {Bleeding and altered iron distribution occur in multiple gastrointestinal diseases, but the importance and regulation of these changes remain unclear. We found that hepcidin, the master regulator of systemic iron homeostasis, is required for tissue repair in the mouse intestine after experimental damage. This effect was independent of hepatocyte-derived hepcidin or systemic iron levels. Rather, we identified conventional dendritic cells (cDCs) as a source of hepcidin that is induced by microbial stimulation in mice, prominent in the inflamed intestine of humans, and essential for tissue repair. cDC-derived hepcidin acted on ferroportin-expressing phagocytes to promote local iron sequestration, which regulated the microbiota and consequently facilitated intestinal repair. Collectively, these results identify a pathway whereby cDC-derived hepcidin promotes mucosal healing in the intestine through means of nutritional immunity.}, }
@article {pmid32272276, year = {2020}, author = {Liu, C and Cheng, L and Ji, L and Li, F and Zhan, Y and Wu, B and Ke, Y and Chen, P and Hua, F and Yuan, L and Min, Z and Sun, L and Chen, H and Cheng, Y}, title = {Intestinal microbiota dysbiosis play a role in pathogenesis of patients with primary immune thrombocytopenia.}, journal = {Thrombosis research}, volume = {190}, number = {}, pages = {11-19}, doi = {10.1016/j.thromres.2020.03.012}, pmid = {32272276}, issn = {1879-2472}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Phylogeny ; *Purpura, Thrombocytopenic, Idiopathic ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The intestinal microbiota is essential for the maintenance of the physiology of immune homeostasis. Dysbiosis has been described in some autoimmune diseases, however its role is still elusive in primary immune thrombocytopenia (ITP), which is one kind of autoimmune diseases. This study aimed to characterize the phylogenetic diversity of the fecal microbiota and its relationship with the platelet activation status in patients with ITP.<br><br>METHODS: The platelet activation status was assessed by 2 platelet markers, PAC-1 (antibody that recognizes the activated GPIIb/IIIa complex) and CD62p (Platelet surface P-selectin) by flow cytometry. Total DNA was extracted from fecal samples of ITP patients and healthy controls (HC). Sequencing the V4 hypervariable region of bacterial 16S rRNA genes was used to identify the changes in phylogenetic diversity and composition of the intestinal flora. The obtained sequencing reads were assigned to operational taxonomic units (OTUs, 97% sequence identity) and taxonomically classified to assess composition and diversity.<br><br>RESULTS: The percentage of PAC-1+ platelets in ITP patients was higher than that in control group (p&#xa0;<&#xa0;0.001), The percentage of CD62p+ and PAC-1+CD62p+ platelets in ITP patients both higher than those in control group (p&#xa0;<&#xa0;0.001). At the phylum level, eight different phyla were identified in ITP individuals, with a majority of Bacteroidetes (45.96%) and Firmicutes (38.59%), followed by Proteobacteria (11.43%), Fusobacteria(1.29%), and Actinobacteria (1.22%). While in the Healthy volunteers, ten phyla were detected, with a predominance of Firmicutes (50.92%) and Bacteroidetes (34.26%), came before Proteobacteria (13.60%), and Actinobacteria (0.90%). The gut microbiota was skewed in ITP, with an increased proportion of Proteobacteria, Bacteroidetes and Bacteroidetes/Firmicutes ratio, a decreased proportion of Firmicutes compared with HC. Disease specific alterations in diversity was also identified, especially the potential markers (Anaerorhabdus, sutterella, Peptostreptococcaceae, Clostridium_XI and carnobacteriaceae, p&#xa0;<&#xa0;0.05) for ITP.<br><br>CONCLUSIONS: The results suggested that the distinct microbiota dysbiosis in ITP characterized by alterations in biodiversity and composition, which could provide insights for diet therapy and fecal microbiota transplantation treatment to cure ITP. There might be somehow compensatory enhancement of platelet activation in ITP patients. And there is associate between platelet activation and intestinal microbiota in patients with ITP.}, }
@article {pmid32267559, year = {2020}, author = {Demir, M and Lang, S and Martin, A and Farowski, F and Wisplinghoff, H and Vehreschild, MJGT and Krawczyk, M and Nowag, A and Scholz, CJ and Kretzschmar, A and Roderburg, C and Lammert, F and Goeser, T and Kasper, P and Steffen, HM}, title = {Phenotyping non-alcoholic fatty liver disease by the gut microbiota: Ready for prime time?.}, journal = {Journal of gastroenterology and hepatology}, volume = {35}, number = {11}, pages = {1969-1977}, doi = {10.1111/jgh.15071}, pmid = {32267559}, issn = {1440-1746}, support = {160/2014 (to M.D.)//K&#xf6;ln Fortune/ ; 210-03-2016//Marga und Walter Boll-Stiftung/ ; }, mesh = {Adult ; Bacteroidetes ; Cross-Sectional Studies ; Female ; *Gastrointestinal Microbiome/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lactobacillaceae ; Male ; Non-alcoholic Fatty Liver Disease/*genetics/*microbiology ; *Phenotype ; Prospective Studies ; RNA, Ribosomal, 16S ; Ruminococcus ; Veillonella ; Young Adult ; }, abstract = {BACKGROUND AND AIM: Several studies observed alterations in the gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD). However, analyzed patient populations and methods strongly differ among these studies. The aim of this study was to prove the reproducibility of published results and to provide a detailed overview of all findings in our NAFLD cohort using next generation sequencing methods.<br><br>METHODS: The individual taxonomic microbiota composition of fecal samples from 90 NAFLD patients and 21 healthy controls was analyzed using 16S rRNA gene sequencing. Study participants were grouped according to their disease stage and compared regarding their gut microbiota composition. Studies were identified from PubMed listed publications, and the results were compared with the findings in our cohort.<br><br>RESULTS: Results from 13 identified studies were compared with our data. A decreased abundance of the Bacteroidetes and Ruminococcaceae as well as an increased abundance of Lactobacillaceae and Veillonellaceae and Dorea were the most frequently reported changes among NAFLD patients in 4/13, 5/13, 4/13, 2/13, and 3/13 studies, respectively. Even though these alterations in the gut microbiota composition were also observed in our patient cohort, the majority of published differences could not be reproduced, neither in our own nor in other NAFLD cohort studies.<br><br>CONCLUSION: Despite repeatedly reproduced abundance patterns of specific bacteria, the heterogeneous study results did not reveal a consistent disease specific gut microbiota signature. Further prospective studies with homogenous patient cohorts and standardized methods are necessary to phenotype NAFLD by the gut microbiota.}, }
@article {pmid32266849, year = {2020}, author = {Boem, F and Nannini, G and Amedei, A}, title = {Not just 'immunity': how the microbiota can reshape our approach to cancer immunotherapy.}, journal = {Immunotherapy}, volume = {12}, number = {6}, pages = {407-416}, doi = {10.2217/imt-2019-0192}, pmid = {32266849}, issn = {1750-7448}, mesh = {*Gastrointestinal Microbiome ; Humans ; Immune System ; Immunologic Factors ; Immunotherapy/methods ; *Microbiota ; *Neoplasms/therapy ; }, abstract = {Cancer immunotherapy refers to a set of approaches aiming at enhancing the immune system to fight cancer growth and spread. This variety of therapeutic approaches, especially those inhibiting immune checkpoints, have shown very promising results. Nevertheless, patients may respond differently to treatments and the efficacy of immunotherapy seems to be dependent on several factors that go beyond the molecular targeting of immune cells modulation. Here, we review how the activity of gut microbiota appears to be crucial in determining the effectiveness of some immunotherapeutic treatments, fostering or impeding the conditions under which treatments can work or not. Moreover, we discuss how these findings suggest not only extending the range of immunotherapeutic approaches but also reshaping our understanding of immunotherapy itself.}, }
@article {pmid32266848, year = {2020}, author = {Voth, E and Khanna, S}, title = {Fecal microbiota transplantation for treatment of patients with recurrent Clostridioides difficile infection.}, journal = {Expert review of anti-infective therapy}, volume = {18}, number = {7}, pages = {669-676}, doi = {10.1080/14787210.2020.1752192}, pmid = {32266848}, issn = {1744-8336}, mesh = {Anti-Bacterial Agents/administration &amp; dosage ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; *Gastrointestinal Microbiome ; Humans ; Recurrence ; Risk Factors ; }, abstract = {INTRODUCTION: Recurrent Clostridiodes difficile infection (rCDI) is a growing public health burden, and is associated with poor patient outcomes. Fecal microbiota transplantation (FMT) is a novel therapy with an aim to restore the disrupted microbiota with demonstrated success in the management of rCDI and a favorable safety profile.<br><br>AREAS COVERED: This review includes a comprehensive overview of a search of the literature including epidemiology of rCDI, basics of the gut microbiome, antibiotic therapy for rCDI along with rationale for safety and efficacy of FMT for rCDI.<br><br>EXPERT OPINION: Patients exposed to risk factors, such as antimicrobial agents, are at risk for disruption of the gut microbiome resulting in the reduction of microbial diversity and dysbiosis. Dysbiotic microbiota predispose to primary and rCDI. Strategies to improve the current and future management of rCDI are under clinical investigation, including narrow-spectrum antibiotics, monoclonal antibodies and FMT, which has shown a high success rate for rCDI. Further investigation is needed to determine optimal standardization of the methodological components of FMT including donor screening, stool preparation, storage and instillation and patient follow-up. Newer methods of microbiota replacement therapies including enema- and capsule-based therapies are under investigation.}, }
@article {pmid32266160, year = {2020}, author = {Vendrik, KEW and Ooijevaar, RE and de Jong, PRC and Laman, JD and van Oosten, BW and van Hilten, JJ and Ducarmon, QR and Keller, JJ and Kuijper, EJ and Contarino, MF}, title = {Fecal Microbiota Transplantation in Neurological Disorders.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {98}, pmid = {32266160}, issn = {2235-2988}, mesh = {Animals ; *Autism Spectrum Disorder ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Nervous System Diseases/therapy ; Treatment Outcome ; }, abstract = {Background: Several studies suggested an important role of the gut microbiota in the pathophysiology of neurological disorders, implying that alteration of the gut microbiota might serve as a treatment strategy. Fecal microbiota transplantation (FMT) is currently the most effective gut microbiota intervention and an accepted treatment for recurrent Clostridioides difficile infections. To evaluate indications of FMT for patients with neurological disorders, we summarized the available literature on FMT. In addition, we provide suggestions for future directions. Methods: In July 2019, five main databases were searched for studies and case descriptions on FMT in neurological disorders in humans or animal models. In addition, the ClinicalTrials.gov website was consulted for registered planned and ongoing trials. Results: Of 541 identified studies, 34 were included in the analysis. Clinical trials with FMT have been performed in patients with autism spectrum disorder and showed beneficial effects on neurological symptoms. For multiple sclerosis and Parkinson's disease, several animal studies suggested a positive effect of FMT, supported by some human case reports. For epilepsy, Tourette syndrome, and diabetic neuropathy some studies suggested a beneficial effect of FMT, but evidence was restricted to case reports and limited numbers of animal studies. For stroke, Alzheimer's disease and Guillain-Barré syndrome only studies with animal models were identified. These studies suggested a potential beneficial effect of healthy donor FMT. In contrast, one study with an animal model for stroke showed increased mortality after FMT. For Guillain-Barré only one study was identified. Whether positive findings from animal studies can be confirmed in the treatment of human diseases awaits to be seen. Several trials with FMT as treatment for the above mentioned neurological disorders are planned or ongoing, as well as for amyotrophic lateral sclerosis. Conclusions: Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders. However, available evidence is still scanty and some contrasting results were observed. A limited number of studies in humans have been performed or are ongoing, while for some disorders only animal experiments have been conducted. Large double-blinded randomized controlled trials are needed to further elucidate the effect of FMT in neurological disorders.}, }
@article {pmid32256746, year = {2020}, author = {Chen, HT and Huang, HL and Xu, HM and Luo, QL and He, J and Li, YQ and Zhou, YL and Nie, YQ and Zhou, YJ}, title = {Fecal microbiota transplantation ameliorates active ulcerative colitis.}, journal = {Experimental and therapeutic medicine}, volume = {19}, number = {4}, pages = {2650-2660}, pmid = {32256746}, issn = {1792-0981}, abstract = {Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.}, }
@article {pmid32255522, year = {2020}, author = {Du, HX and Liu, Y and Zhang, LG and Zhan, CS and Chen, J and Zhang, M and Chen, XG and Zhang, L and Liang, CZ}, title = {Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis-induced depressive-like behaviors in mice.}, journal = {The Prostate}, volume = {80}, number = {9}, pages = {663-673}, doi = {10.1002/pros.23978}, pmid = {32255522}, issn = {1097-0045}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Behavior, Animal/*physiology ; Chronic Disease ; Depression/immunology/*microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/immunology/*physiology ; Male ; Mice ; Mice, Inbred NOD ; Prostatitis/immunology/*microbiology/*psychology ; Random Allocation ; }, abstract = {BACKGROUND: Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP).<br><br>METHODS: Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression-like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on host behaviors and the composition of gut bacteria.<br><br>RESULTS: EAP was successfully established and exhibited depressive-like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics-treated pseudo-germ-free mice presented depressive states as compared to na&#xef;ve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo-germ-free mice, significantly exaggerated host depression-like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in &#x3b1;-diversity and &#x3b2;-diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation.<br><br>CONCLUSIONS: Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition.}, }
@article {pmid32255488, year = {2021}, author = {McGovern, BH and Ford, CB and Henn, MR and Pardi, DS and Khanna, S and Hohmann, EL and O'Brien, EJ and Desjardins, CA and Bernardo, P and Wortman, JR and Lombardo, MJ and Litcofsky, KD and Winkler, JA and McChalicher, CWJ and Li, SS and Tomlinson, AD and Nandakumar, M and Cook, DN and Pomerantz, RJ and Auninš, JG and Trucksis, M}, title = {SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {72}, number = {12}, pages = {2132-2140}, pmid = {32255488}, issn = {1537-6591}, mesh = {Aged ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/drug therapy/prevention &amp; control ; Drugs, Investigational ; Female ; Humans ; Male ; *Microbiota ; Recurrence ; }, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (rCDI) is associated with loss of microbial diversity and microbe-derived secondary bile acids, which inhibit C. difficile germination and growth. SER-109, an investigational microbiome drug of donor-derived, purified spores, reduced recurrence in a dose-ranging, phase (P) 1 study in subjects with multiple rCDIs.<br><br>METHODS: In a P2 double-blind trial, subjects with clinical resolution on standard-of-care antibiotics were stratified by age (< or &#x2265;65 years) and randomized 2:1 to single-dose SER-109 or placebo. Subjects were diagnosed at study entry by PCR or toxin testing. Safety, C. difficile-positive diarrhea through week 8, SER-109 engraftment, and bile acid changes were assessed.<br><br>RESULTS: 89 subjects enrolled (67% female; 80.9% diagnosed by PCR). rCDI rates were lower in the SER-109 arm than placebo (44.1% vs 53.3%) but did not meet statistical significance. In a preplanned analysis, rates were reduced among subjects &#x2265;65 years (45.2% vs 80%, respectively; RR, 1.77; 95% CI, 1.11-2.81), while the <65 group showed no benefit. Early engraftment of SER-109 was associated with nonrecurrence (P < .05) and increased secondary bile acid concentrations (P < .0001). Whole-metagenomic sequencing from this study and the P1 study revealed previously unappreciated dose-dependent engraftment kinetics and confirmed an association between early engraftment and nonrecurrence. Engraftment kinetics suggest that P2 dosing was suboptimal. Adverse events were generally mild to moderate in severity.<br><br>CONCLUSIONS: Early SER-109 engraftment was associated with reduced CDI recurrence and favorable safety was observed. A higher dose of SER-109 and requirements for toxin testing were implemented in the current P3 trial.<br><br>CLINICAL TRIALS REGISTRATION: NCT02437487, https://clinicaltrials.gov/ct2/show/NCT02437487?term=SER-109&amp;draw= 2&amp;rank=4.}, }
@article {pmid32253791, year = {2020}, author = {Hughes, KR and Schofield, Z and Dalby, MJ and Caim, S and Chalklen, L and Bernuzzi, F and Alcon-Giner, C and Le Gall, G and Watson, AJM and Hall, LJ}, title = {The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {34}, number = {5}, pages = {7075-7088}, pmid = {32253791}, issn = {1530-6860}, support = {BB/M011216/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J004529/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 100974/C/13/Z/WT_/Wellcome Trust/United Kingdom ; 100974/WT_/Wellcome Trust/United Kingdom ; BBS/E/F/00044409/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10355/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Animals, Newborn/metabolism/*microbiology ; Anti-Bacterial Agents/administration &amp; dosage ; Bile Acids and Salts/metabolism ; Epithelial Cells/metabolism/pathology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/drug effects/genetics/*physiology ; Host Microbial Interactions/drug effects/physiology ; Inflammation/metabolism/microbiology/pathology ; Intestinal Mucosa/metabolism/*microbiology/*pathology ; Intestine, Small/metabolism/microbiology/pathology ; Lipopolysaccharides/administration &amp; dosage ; Mice ; Mice, Inbred C57BL ; Signal Transduction ; }, abstract = {The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation.}, }
@article {pmid32252520, year = {2020}, author = {Teng, T and Gao, F and He, W and Fu, H and Guo, J and Bai, G and Shi, B}, title = {An Early Fecal Microbiota Transfer Improves the Intestinal Conditions on Microflora and Immunoglobulin and Antimicrobial Peptides in Piglets.}, journal = {Journal of agricultural and food chemistry}, volume = {68}, number = {17}, pages = {4830-4843}, doi = {10.1021/acs.jafc.0c00545}, pmid = {32252520}, issn = {1520-5118}, mesh = {Animals ; Animals, Newborn/*immunology/microbiology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Immunoglobulin G/*immunology ; Intestinal Mucosa/immunology/microbiology ; Jejunum/immunology/microbiology ; Male ; Pore Forming Cytotoxic Proteins/*immunology ; Swine ; }, abstract = {The goal of this study was to investigate the effects of early fecal microbial transfer (FMT) on the microflora of recipient piglets, where Yorkshire newborn piglets and Min sows (an indigenous pig breed in China) were used as the fecal recipients and donors, respectively, to reveal the changes in immunity and development-related functions of the intestinal mucosa driven by FMT. The recipient group was inoculated with fecal microbial fluids from days 1 to 10. On day 21, the relative abundance of the Proteobacteria was reduced; the concentrations of immunoglobulin M (IgM) and immunoglobulin G (IgG) in the jejunal mucosa, and that of IgG in the ileal mucosa of the recipient group, were increased (P < 0.05). On day 40, the relative abundance of the Firmicutes in the recipient group was increased, while that of Bacteroides was decreased. The concentrations of IgG and IgM in the ileal mucosa of the recipient group were increased. FMT protected the intestine by modulating the antimicrobial peptides of the intestinal mucosa (P < 0.05). The results of this study revealed that early FMT can improve the gut microbiota, intestinal mucosal immunity, and intestinal development-related functions of Yorkshire piglets.}, }
@article {pmid32251667, year = {2020}, author = {Pickert, G and Wirtz, S and Matzner, J and Ashfaq-Khan, M and Heck, R and Rosigkeit, S and Thies, D and Surabattula, R and Ehmann, D and Wehkamp, J and Aslam, M and He, G and Weigert, A and Foerster, F and Klotz, L and Frick, JS and Becker, C and Bockamp, E and Schuppan, D}, title = {Wheat Consumption Aggravates Colitis in Mice via Amylase Trypsin Inhibitor-mediated Dysbiosis.}, journal = {Gastroenterology}, volume = {159}, number = {1}, pages = {257-272.e17}, doi = {10.1053/j.gastro.2020.03.064}, pmid = {32251667}, issn = {1528-0012}, mesh = {Animal Feed/adverse effects ; Animals ; Colitis/chemically induced/diagnosis/*immunology/microbiology ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Dysbiosis/complications/diagnosis/*immunology/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/immunology ; Humans ; Immunity, Innate ; Inflammatory Bowel Diseases/chemically induced/diagnosis/*immunology/microbiology ; Male ; Mice ; Mice, Knockout ; Plant Proteins, Dietary/*adverse effects/immunology ; Severity of Illness Index ; Signal Transduction/genetics/immunology ; Toll-Like Receptor 4/genetics/metabolism ; Triticum/*immunology ; Trypsin Inhibitors/adverse effects/immunology ; }, abstract = {BACKGROUND &amp; AIMS: Wheat has become the world's major staple and its consumption correlates with prevalence of noncommunicable disorders such as inflammatory bowel diseases. Amylase trypsin inhibitors (ATIs), a component of wheat, activate the intestine's innate immune response via toll-like receptor 4 (TLR4). We investigated the effects of wheat and ATIs on severity of colitis and fecal microbiota in mice.<br><br>METHODS: C57BL/6 wild-type and Tlr4[-/-] mice were fed wheat- or ATI-containing diets or a wheat-free (control) diet and then given dextran sodium sulfate to induce colitis; we also studied Il10[-/-] mice, which develop spontaneous colitis. Changes in fecal bacteria were assessed by taxa-specific quantitative polymerase chain reaction and 16S ribosomal RNA metagenomic sequencing. Feces were collected from mice on wheat-containing, ATI-containing, control diets and transplanted to intestines of mice with and without colitis on control or on ATI-containing diets. Intestinal tissues were collected and analyzed by histology, immunohistochemistry, and flow cytometry. Bacteria with reported immunomodulatory effects were incubated with ATIs and analyzed in radial diffusion assays.<br><br>RESULTS: The wheat- or ATI-containing diets equally increased inflammation in intestinal tissues of C57BL/6 mice with colitis, compared with mice on control diets. The ATI-containing diet promoted expansion of taxa associated with development of colitis comparable to the wheat-containing diet. ATIs inhibited proliferation of specific human commensal bacteria in radial diffusion assays. Transplantation of microbiota from feces of mice fed the wheat- or ATI-containing diets to intestines of mice on control diets increased the severity of colitis in these mice. The ATI-containing diet did not increase the severity of colitis in Tlr4[-/-] mice.<br><br>CONCLUSIONS: Consumption of wheat or wheat ATIs increases intestinal inflammation in mice with colitis, via TLR4, and alters their fecal microbiota. Wheat-based, ATI-containing diets therefore activate TLR4 signaling and promote intestinal dysbiosis.}, }
@article {pmid32251347, year = {2020}, author = {Afouda, P and Hocquart, M and Pham, TP and Kuete, E and Ngom, II and Dione, N and Valles, C and Bellali, S and Lagier, JC and Dubourg, G and Raoult, D}, title = {Alcohol pretreatment of stools effect on culturomics.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {5190}, pmid = {32251347}, issn = {2045-2322}, mesh = {Actinobacteria/drug effects/isolation &amp; purification ; Adult ; Aged ; Bacteria/drug effects/*isolation &amp; purification ; *Bacteriological Techniques ; Bacteroidetes/drug effects/isolation &amp; purification ; Clostridioides difficile/*drug effects/isolation &amp; purification/physiology ; Clostridium Infections/*therapy ; Disinfection ; Ethanol/*pharmacology ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Firmicutes/drug effects/isolation &amp; purification ; *Gastrointestinal Microbiome ; Humans ; Male ; Proteobacteria/drug effects/isolation &amp; purification ; Species Specificity ; Specimen Handling/*methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Spores, Bacterial/drug effects ; Succinates/metabolism ; }, abstract = {Recent studies have used ethanol stool disinfection as a mean of promoting valuable species' cultivation in bacteriotherapy trials for Clostridium difficile infections (CDI) treatment with a particular focus on sporulating bacteria. Moreover, the culturomic approach has considerably enriched the repertoire of cultivable organisms in the human gut in recent years. This study aimed to apply this culturomic approach on fecal donor samples treated with ethanol disinfection to evidence potential beneficial microbes that could be used in bacteriotherapy trials for the treatment of CDI. Thereby, a total of 254 bacterial species were identified, 9 of which were novel. Of these, 242 have never been included in clinical trials for the treatment of CDIs, representing potential new candidates for bacteriotherapy trials. While non-sporulating species were nevertheless more affected by the ethanol pretreatment than sporulating species, the ethanol disinfection technique did not specifically select bacteria able to sporulate, as suggested by previous studies. Furthermore, some bacteria previously considered as potential candidates for bacteriotherapy have been lost after ethanol treatment. This study, while enriching the bacterial repertoire of the human intestine, would nevertheless require determining the exact contribution of each of species composing the bacterial consortia intended to be administered for CDI treatment.}, }
@article {pmid32250997, year = {2020}, author = {Shah, A and Macdonald, GA and Morrison, M and Holtmann, G}, title = {Targeting the Gut Microbiome as a Treatment for Primary Sclerosing Cholangitis: A Conceptional Framework.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {6}, pages = {814-822}, pmid = {32250997}, issn = {1572-0241}, mesh = {Anti-Infective Agents/*therapeutic use ; Bile Acids and Salts/*metabolism ; Cholangitis, Sclerosing/immunology/metabolism/microbiology/*therapy ; Dysbiosis/immunology/metabolism/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunity, Mucosal/immunology ; Inflammatory Bowel Diseases/immunology/metabolism/*microbiology ; Intestinal Mucosa/immunology/metabolism/microbiology ; Liver Transplantation ; }, abstract = {Primary sclerosing cholangitis (PSC) is a rare, immune-mediated, chronic cholestatic liver disease associated with a unique phenotype of inflammatory bowel disease that frequently manifests as pancolitis with right-sided predominance. Available data suggest a bidirectional interplay of the gut-liver axis with critical roles for the gastrointestinal microbiome and circulating bile acids (BAs) in the pathophysiology of PSC. BAs shape the gut microbiome, whereas gut microbes have the potential to alter BAs, and there are emerging data that alterations of BAs and the microbiome are not simply a consequence but the cause of PSC. Clustering of PSC in families may suggest that PSC occurs in genetically susceptible individuals. After exposure to an environmental trigger (e.g., microbial byproducts or BAs), an aberrant or exaggerated cholangiocyte-induced immune cascade occurs, ultimately leading to bile duct damage and progressive fibrosis. The pathophysiology can be conceptualized as a triad of (1) gut dysbiosis, (2) altered BA metabolism, and (3) immune-mediated biliary injury. Immune activation seems to be central to the disease process, but immunosuppression does not improve clinical outcomes or alter the natural history of PSC. Currently, orthoptic liver transplantation is the only established life-saving treatment, whereas antimicrobial therapy or fecal transplantation is an emerging therapeutic option for PSC. The beneficial effects of these microbiome-based therapies are likely mediated by a shift of the gut microbiome with favorable effects on BA metabolism. In the future, personalized approaches will allow to better target the interdependence between microbiome, immune function, and BA metabolism and potentially cure patients with PSC.}, }
@article {pmid32250972, year = {2020}, author = {Mennini, M and Fierro, V and Di Nardo, G and Pecora, V and Fiocchi, A}, title = {Microbiota in non-IgE-mediated food allergy.}, journal = {Current opinion in allergy and clinical immunology}, volume = {20}, number = {3}, pages = {323-328}, doi = {10.1097/ACI.0000000000000644}, pmid = {32250972}, issn = {1473-6322}, mesh = {Bacteroidetes/immunology ; Dietary Proteins/immunology ; Dysbiosis/diagnosis/*immunology/microbiology ; Enteritis/epidemiology/immunology/microbiology ; Eosinophilia/epidemiology/immunology/microbiology ; Eosinophilic Esophagitis/epidemiology/immunology/microbiology ; Feces/microbiology ; Food Hypersensitivity/epidemiology/*immunology/microbiology ; Gastritis/epidemiology/immunology/microbiology ; Gastrointestinal Microbiome/*immunology ; Humans ; Prevalence ; Proctocolitis/epidemiology/immunology/microbiology ; Proteobacteria/immunology/isolation &amp; purification ; }, abstract = {PURPOSE OF REVIEW: To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy.<br><br>RECENT FINDINGS: The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota.<br><br>SUMMARY: Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.}, }
@article {pmid32247350, year = {2020}, author = {Cho, JM and Pardi, DS and Khanna, S}, title = {Update on Treatment of Clostridioides difficile Infection.}, journal = {Mayo Clinic proceedings}, volume = {95}, number = {4}, pages = {758-769}, doi = {10.1016/j.mayocp.2019.08.006}, pmid = {32247350}, issn = {1942-5546}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; Clostridium Infections/drug therapy/microbiology/*therapy ; Fecal Microbiota Transplantation ; Humans ; Probiotics/therapeutic use ; Recurrence ; }, abstract = {Clostridioides difficile infection (CDI) is the leading cause of health care-associated infections in the United States. The increasing incidence and recurrence rates of CDI together with its associated morbidity and mortality are great concerns. Newer treatment methods, such as narrow-spectrum antibiotics, monoclonal antibodies, and microbial replacement therapies, are being developed and implemented. We searched PubMed to identify published literature from 2010 to 2018 using the following keywords: Clostridium difficile, treatment, and therapy. Cited references were also used to identify relevant literature. This review focuses on the current standard of therapy and emerging therapies for CDI and summarizes the updated guidelines on treatment of CDI.}, }
@article {pmid32245535, year = {2020}, author = {Alimirah, M and Sadiq, O and Gordon, SC}, title = {Novel Therapies in Hepatic Encephalopathy.}, journal = {Clinics in liver disease}, volume = {24}, number = {2}, pages = {303-315}, doi = {10.1016/j.cld.2020.01.009}, pmid = {32245535}, issn = {1557-8224}, mesh = {Acetylcarnitine/therapeutic use ; Albumins/therapeutic use ; Ammonia/blood ; Dipeptides/therapeutic use ; *Fecal Microbiota Transplantation ; Flumazenil/therapeutic use ; GABA Modulators/therapeutic use ; Glycerol/analogs &amp; derivatives/therapeutic use ; Hepatic Encephalopathy/blood/etiology/*therapy ; Humans ; Nootropic Agents/therapeutic use ; Ornithine/analogs &amp; derivatives/therapeutic use ; Phenylbutyrates/therapeutic use ; Polyethylene Glycols/therapeutic use ; Probiotics ; Surface-Active Agents/therapeutic use ; }, abstract = {Despite widespread use of lactulose and rifaximin for the treatment of hepatic encephalopathy, this complication of advanced liver disease remains a major burden on the health care system in the United States and continues to predispose to high morbidity and mortality. Several agents have surfaced over recent years with promise to treat hepatic encephalopathy and mitigate the cognitive impairment associated with this disease process. The purpose of this article is to highlight the leading emerging therapies in hepatic encephalopathy as well as their therapeutic targets.}, }
@article {pmid32245531, year = {2020}, author = {Weir, V and Reddy, KR}, title = {Nonpharmacologic Management of Hepatic Encephalopathy: An Update.}, journal = {Clinics in liver disease}, volume = {24}, number = {2}, pages = {243-261}, doi = {10.1016/j.cld.2020.01.003}, pmid = {32245531}, issn = {1557-8224}, mesh = {Amino Acids, Branched-Chain/therapeutic use ; Dietary Proteins/administration &amp; dosage ; Energy Intake ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Hepatic Encephalopathy/etiology/*therapy ; Humans ; Liver Transplantation ; Liver, Artificial ; Prebiotics ; Probiotics/therapeutic use ; Synbiotics ; }, abstract = {Research increasingly shows that the gut-liver-brain axis is a crucial component in the pathophysiology of hepatic encephalopathy (HE). Due to the limitations of current standard-of-care medications, non-pharmacological treatments that target gut dysbiosis, including probiotics, nutritional management, and fecal microbiota transplants, are being considered as alternative and adjunct therapies. Meta-analyses note that probiotics could offer benefits in HE treatment, but have not shown superiority over lactulose. Emerging literature suggests that fecal microbiota transplants could offer a novel strategy to treat gut dysbiosis and favorably impact HE. Finally, liver support devices and liver transplantation could offer a last-resort treatment option for persistent HE.}, }
@article {pmid32245530, year = {2020}, author = {Mahpour, NY and Pioppo-Phelan, L and Reja, M and Tawadros, A and Rustgi, VK}, title = {Pharmacologic Management of Hepatic Encephalopathy.}, journal = {Clinics in liver disease}, volume = {24}, number = {2}, pages = {231-242}, doi = {10.1016/j.cld.2020.01.005}, pmid = {32245530}, issn = {1557-8224}, mesh = {Acarbose/therapeutic use ; Amino Acids, Branched-Chain/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Dipeptides/therapeutic use ; Fecal Microbiota Transplantation ; Flumazenil/therapeutic use ; GABA Modulators/therapeutic use ; Glycerol/analogs &amp; derivatives/therapeutic use ; Glycoside Hydrolase Inhibitors/therapeutic use ; Hepatic Encephalopathy/*therapy ; Humans ; Lactulose/therapeutic use ; Laxatives/*therapeutic use ; Phenylbutyrates/therapeutic use ; Probiotics/therapeutic use ; Rifaximin/*therapeutic use ; }, abstract = {Pharmacologic management of hepatic encephalopathy includes a broad range of therapies. This article covers the specific mainstays of therapies, such as antimicrobials and laxatives, with an established evidence base. This article also covers newer modalities of therapies, such as fecal microbiota transplant, probiotics, bioartificial support systems, small molecular therapies such as l-ornithine l-aspartate, branched chain amino acids, l-carnitine, zinc, and other forms of therapy currently under review.}, }
@article {pmid32243790, year = {2020}, author = {}, title = {Translating Microbiome Research into Therapies: The Path Ahead.}, journal = {Cell}, volume = {181}, number = {1}, pages = {20-21}, doi = {10.1016/j.cell.2020.03.009}, pmid = {32243790}, issn = {1097-4172}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Probiotics/*therapeutic use ; *Translational Research, Biomedical ; }, }
@article {pmid32241904, year = {2020}, author = {Wang, X and Yang, S and Li, S and Zhao, L and Hao, Y and Qin, J and Zhang, L and Zhang, C and Bian, W and Zuo, L and Gao, X and Zhu, B and Lei, XG and Gu, Z and Cui, W and Xu, X and Li, Z and Zhu, B and Li, Y and Chen, S and Guo, H and Zhang, H and Sun, J and Zhang, M and Hui, Y and Zhang, X and Liu, X and Sun, B and Wang, L and Qiu, Q and Zhang, Y and Li, X and Liu, W and Xue, R and Wu, H and Shao, D and Li, J and Zhou, Y and Li, S and Yang, R and Pedersen, OB and Yu, Z and Ehrlich, SD and Ren, F}, title = {Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents.}, journal = {Gut}, volume = {69}, number = {12}, pages = {2131-2142}, pmid = {32241904}, issn = {1468-3288}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Case-Control Studies ; Disease Models, Animal ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Kidney Failure, Chronic/*metabolism ; Male ; *Metabolome ; Mice ; Oxidative Stress ; Rats ; Toxins, Biological/metabolism ; Uremia/metabolism ; }, abstract = {OBJECTIVE: Patients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is to characterise relationships between the intestinal microbiome composition, uraemic toxins and renal failure symptoms in human end-stage renal disease (ESRD).<br><br>DESIGN: Characterisation of gut microbiome, serum and faecal metabolome and human phenotypes in a cohort of 223 patients with ESRD and 69 healthy controls. Multidimensional data integration to reveal links between these datasets and the use of chronic kidney disease (CKD) rodent models to test the effects of intestinal microbiome on toxin accumulation and disease severity.<br><br>RESULTS: A group of microbial species enriched in ESRD correlates tightly to patient clinical variables and encode functions involved in toxin and secondary bile acids synthesis; the relative abundance of the microbial functions correlates with the serum or faecal concentrations of these metabolites. Microbiota from patients transplanted to renal injured germ-free mice or antibiotic-treated rats induce higher production of serum uraemic toxins and aggravated renal fibrosis and oxidative stress more than microbiota from controls. Two of the species, Eggerthella lenta and Fusobacterium nucleatum, increase uraemic toxins production and promote renal disease development in a CKD rat model. A probiotic Bifidobacterium animalis decreases abundance of these species, reduces levels of toxins and the severity of the disease in rats.<br><br>CONCLUSION: Aberrant gut microbiota in patients with ESRD sculpts a detrimental metabolome aggravating clinical outcomes, suggesting that the gut microbiota will be a promising target for diminishing uraemic toxicity in those patients.<br><br>TRIAL REGISTRATION NUMBER: This study was registered at ClinicalTrials.gov (NCT03010696).}, }
@article {pmid32240618, year = {2020}, author = {Green, CA and Quraishi, MN and Shabir, S and Sharma, N and Hansen, R and Gaya, DR and Hart, AL and Loman, NJ and Iqbal, TH}, title = {Screening faecal microbiota transplant donors for SARS-CoV-2 by molecular testing of stool is the safest way forward.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {5}, number = {6}, pages = {531}, pmid = {32240618}, issn = {2468-1253}, support = {MR/J014370/1/MRC_/Medical Research Council/United Kingdom ; MR/M501621/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Betacoronavirus ; COVID-19 ; *Coronavirus Infections ; Humans ; *Microbiota ; Pandemics ; Pneumonia, Viral ; *Severe acute respiratory syndrome-related coronavirus ; SARS-CoV-2 ; }, }
@article {pmid32239720, year = {2020}, author = {Eltokhi, A and Janmaat, IE and Genedi, M and Haarman, BCM and Sommer, IEC}, title = {Dysregulation of synaptic pruning as a possible link between intestinal microbiota dysbiosis and neuropsychiatric disorders.}, journal = {Journal of neuroscience research}, volume = {98}, number = {7}, pages = {1335-1369}, doi = {10.1002/jnr.24616}, pmid = {32239720}, issn = {1097-4547}, mesh = {Animals ; Brain/*physiopathology ; Dysbiosis/complications/*physiopathology ; Gastrointestinal Microbiome/*physiology ; Humans ; Mental Disorders/etiology/*physiopathology ; Neuroglia/physiology ; Neuronal Plasticity/*physiology ; Neurons/physiology ; Synapses/*physiology ; }, abstract = {The prenatal and early postnatal stages represent a critical time window for human brain development. Interestingly, this window partly overlaps with the maturation of the intestinal flora (microbiota) that play a critical role in the bidirectional communication between the central and the enteric nervous systems (microbiota-gut-brain axis). The microbial composition has important influences on general health and the development of several organ systems, such as the gastrointestinal tract, the immune system, and also the brain. Clinical studies have shown that microbiota alterations are associated with a wide range of neuropsychiatric disorders including autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. In this review, we dissect the link between these neuropsychiatric disorders and the intestinal microbiota by focusing on their effect on synaptic pruning, a vital process in the maturation and establishing efficient functioning of the brain. We discuss in detail how synaptic pruning is dysregulated differently in the aforementioned neuropsychiatric disorders and how it can be influenced by dysbiosis and/or changes in the intestinal microbiota composition. We also review that the improvement in the intestinal microbiota composition by a change in diet, probiotics, prebiotics, or fecal microbiota transplantation may play a role in improving neuropsychiatric functioning, which can be at least partly explained via the optimization of synaptic pruning and neuronal connections. Altogether, the demonstration of the microbiota's influence on brain function via microglial-induced synaptic pruning addresses the possibility that the manipulation of microbiota-immune crosstalk represents a promising strategy for treating neuropsychiatric disorders.}, }
@article {pmid32238191, year = {2020}, author = {Tengeler, AC and Dam, SA and Wiesmann, M and Naaijen, J and van Bodegom, M and Belzer, C and Dederen, PJ and Verweij, V and Franke, B and Kozicz, T and Arias Vasquez, A and Kiliaan, AJ}, title = {Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {44}, pmid = {32238191}, issn = {2049-2618}, mesh = {Adult ; Animals ; Attention Deficit Disorder with Hyperactivity/*microbiology/physiopathology ; *Behavior, Animal ; Brain/diagnostic imaging/*physiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Germ-Free Life ; *Host Microbial Interactions ; Humans ; Magnetic Resonance Imaging ; Male ; Mice ; Mice, Inbred C57BL ; Neurodevelopmental Disorders/microbiology ; Young Adult ; }, abstract = {BACKGROUND: The impact of the gut microbiota on host physiology and behavior has been relatively well established. Whether changes in microbial composition affect brain structure and function is largely elusive, however. This is important as altered brain structure and function have been implicated in various neurodevelopmental disorders, like attention-deficit/hyperactivity disorder (ADHD). We hypothesized that gut microbiota of persons with and without ADHD, when transplanted into mice, would differentially modify brain function and/or structure. We investigated this by colonizing young, male, germ-free C57BL/6JOlaHsd mice with microbiota from individuals with and without ADHD. We generated and analyzed microbiome data, assessed brain structure and function by magnetic resonance imaging (MRI), and studied mouse behavior in a behavioral test battery.<br><br>RESULTS: Principal coordinate analysis showed a clear separation of fecal microbiota of mice colonized with ADHD and control microbiota. With diffusion tensor imaging, we observed a decreased structural integrity of both white and gray matter regions (i.e., internal capsule, hippocampus) in mice that were colonized with ADHD microbiota. We also found significant correlations between white matter integrity and the differentially expressed microbiota. Mice colonized with ADHD microbiota additionally showed decreased resting-state functional MRI-based connectivity between right motor and right visual cortices. These regions, as well as the hippocampus and internal capsule, have previously been reported to be altered in several neurodevelopmental disorders. Furthermore, we also show that mice colonized with ADHD microbiota were more anxious in the open-field test.<br><br>CONCLUSIONS: Taken together, we demonstrate that altered microbial composition could be a driver of altered brain structure and function and concomitant changes in the animals' behavior. These findings may help to understand the mechanisms through which the gut microbiota contributes to the pathobiology of neurodevelopmental disorders. Video abstract.}, }
@article {pmid32236095, year = {2020}, author = {Margiotta, E and Miragoli, F and Callegari, ML and Vettoretti, S and Caldiroli, L and Meneghini, M and Zanoni, F and Messa, P}, title = {Gut microbiota composition and frailty in elderly patients with Chronic Kidney Disease.}, journal = {PloS one}, volume = {15}, number = {4}, pages = {e0228530}, pmid = {32236095}, issn = {1932-6203}, mesh = {Aged ; Aged, 80 and over ; Bacteria/isolation &amp; purification ; Cohort Studies ; Feces/microbiology ; Female ; Frail Elderly ; Frailty/*epidemiology ; *Gastrointestinal Microbiome ; Humans ; Male ; Prevalence ; Renal Insufficiency, Chronic/*epidemiology ; }, abstract = {BACKGROUND: Frailty is common in older patients affected by chronic kidney disease (CKD). Since gut microbiota (gMB) may contribute to frailty, we explored possible associations between gMB and frailty in CKD.<br><br>METHODS: We studied 64 CKD patients (stage 3b-4), categorized as frail (F, 38) and not frail (NF, 26) according to Fried criteria, and 15 controls (C), all older than 65 years. In CKD we assessed serum C-reactive protein, blood neutrophil/lymphocyte ratio, Malnutrition-inflammation Score (MIS); gMB was studied by denaturing gel gradient electrophoresis (DGGE), high-throughput sequencing (16S r-RNA gene), and quantitative real-time PCR (RT-PCR).<br><br>RESULTS: No differences in alpha diversity between CKD and C and between F and NF patients emerged, but high-throughput sequencing showed significantly higher abundance of potentially noxious bacteria (Citrobacter, Coprobacillus, etc) and lower abundance of saccharolytic and butyrate-producing bacteria (Prevotella spp., Faecalibacterium prausnitzii, Roseburia spp.), in CKD respect to C. Mogibacteriaceae family and Oscillospira genus abundance was positively related to inflammatory indices in the whole CKD cohort, while that of Akkermansia, Ruminococcus and Eubacterium genera was negatively related. Compared with NF, in F there was a higher abundance of some bacteria (Mogibacteriacee, Coriobacteriacee, Eggerthella, etc), many of which have been described as more abundant in other diseases.<br><br>CONCLUSIONS: These results suggest that inflammation and frailty could be associated to gMB modifications in CKD.}, }
@article {pmid32235826, year = {2020}, author = {Zhu, F and Ju, Y and Wang, W and Wang, Q and Guo, R and Ma, Q and Sun, Q and Fan, Y and Xie, Y and Yang, Z and Jie, Z and Zhao, B and Xiao, L and Yang, L and Zhang, T and Feng, J and Guo, L and He, X and Chen, Y and Chen, C and Gao, C and Xu, X and Yang, H and Wang, J and Dang, Y and Madsen, L and Brix, S and Kristiansen, K and Jia, H and Ma, X}, title = {Metagenome-wide association of gut microbiome features for schizophrenia.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {1612}, pmid = {32235826}, issn = {2041-1723}, mesh = {Animals ; Bacteria/classification/genetics ; Behavior, Animal ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Male ; *Metagenome ; Metagenomics/methods ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; ROC Curve ; Risk Factors ; Schizophrenia/*metabolism/*microbiology ; Social Behavior ; Streptococcus ; }, abstract = {Evidence is mounting that the gut-brain axis plays an important role in mental diseases fueling mechanistic investigations to provide a basis for future targeted interventions. However, shotgun metagenomic data from treatment-naïve patients are scarce hampering comprehensive analyses of the complex interaction between the gut microbiota and the brain. Here we explore the fecal microbiome based on 90 medication-free schizophrenia patients and 81 controls and identify a microbial species classifier distinguishing patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.896, and replicate the microbiome-based disease classifier in 45 patients and 45 controls (AUC = 0.765). Functional potentials associated with schizophrenia include differences in short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters. Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induces deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice. Our findings provide new leads for further investigations in cohort studies and animal models.}, }
@article {pmid32235095, year = {2020}, author = {Veraldi, S and Angileri, L and Rossi, LC and Nazzaro, G}, title = {Endolimax nana and urticaria.}, journal = {Journal of infection in developing countries}, volume = {14}, number = {3}, pages = {321-322}, doi = {10.3855/jidc.12389}, pmid = {32235095}, issn = {1972-2680}, mesh = {Abdominal Pain/etiology ; Adult ; Antiprotozoal Agents/administration &amp; dosage/therapeutic use ; Dysentery, Amebic/complications/*diagnosis/drug therapy ; Endolimax/*isolation &amp; purification ; Feces/parasitology ; Female ; Humans ; Italy ; Metronidazole/administration &amp; dosage/therapeutic use ; *Travel ; Urticaria/etiology ; }, abstract = {Endolimax nana is a commensal protozoan of the colon. We report a case of chronic urticaria associated with E. nana in a 34-year-old Italian woman. The patient suffered from abdominal pain, diarrhoea and weight loss. The disease appeared after a trip to Vietnam. Laboratory examinations showed mild blood eosinophilia. Three coproparasitological examinations were positive for cysts of E. nana. The patient was successfully treated with two courses of metronidazole (2 g/day for 10 days each). No antihistamines were used. Three coproparasitological examinations, carried out at the end of the therapy, were negative. Follow up (six months) was negative. E. nana can be responsible for very rare cases of abdominal pain, diarrhoea, polyarthritis and urticaria.}, }
@article {pmid32234317, year = {2020}, author = {Liu, J and Miyake, H and Zhu, H and Li, B and Alganabi, M and Lee, C and Pierro, A}, title = {Fecal microbiota transplantation by enema reduces intestinal injury in experimental necrotizing enterocolitis.}, journal = {Journal of pediatric surgery}, volume = {55}, number = {6}, pages = {1094-1098}, doi = {10.1016/j.jpedsurg.2020.02.035}, pmid = {32234317}, issn = {1531-5037}, mesh = {Animals ; Animals, Newborn ; Case-Control Studies ; Disease Models, Animal ; Enema/*methods ; Enterocolitis, Necrotizing/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Hypoxia ; Ileum/pathology ; Infant, Newborn ; Inflammation/pathology ; Intestinal Mucosa/pathology ; Intestines/pathology ; Mice ; Mice, Inbred C57BL ; }, abstract = {PURPOSE: Necrotizing Enterocolitis (NEC) is a devastating neonatal disease with a high mortality rate. Fecal Microbiota Transplantation (FMT) has been used to treat a variety of gastrointestinal diseases. We aimed to investigate the role of FMT in NEC.<br><br>METHODS: NEC was induced by hypoxia, LPS, and hyperosmolar gavage feeding between postnatal days P5 and P9 (n&#x202f;=&#x202f;8). Breastfed mice were used as control (n&#x202f;=&#x202f;7). FMT (30&#x202f;&#x3bc;l/g) was administered by gavage or enema at P6 during NEC induction. Distal ileum was harvested on P9. Disease severity was evaluated by H&amp;E staining. Gene expression of inflammatory markers IL6 and TNFa was measured. Expression of intestinal barrier function was investigated by measuring Claudin-7. Microbiota composition in ileum and colon was analyzed by quantitative PCR.<br><br>RESULTS: FMT by gavage further increased terminal ileum inflammation and did not improve the histological damage owing to experimental NEC. Conversely, FMT by enema decreased intestinal inflammation and improved histology of the NEC-like injury in the ileum. In addition, compared with NEC alone, FMT by enema increased Claudin-7 expression indicating an improvement in barrier function. These beneficial effects occurred despite no change in microbiota.<br><br>CONCLUSION: Our results show that FMT by enema may be an effective strategy to reduce NEC progression as it attenuates intestinal inflammation and enhances intestinal barrier function. FMT by enema is a potential novel treatment for NEC.<br><br>LEVEL OF EVIDENCE: Level IV, Evidence from well-designed case-control or cohort studies.}, }
@article {pmid32233326, year = {2019}, author = {Trang-Poisson, C}, title = {[Fecal transplantation].}, journal = {La Revue du praticien}, volume = {69}, number = {7}, pages = {792-793}, pmid = {32233326}, issn = {2101-017X}, mesh = {*Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; }, }
@article {pmid32233325, year = {2019}, author = {Barbut, F and Couturier, J}, title = {[Interactions between intestinal microbiota and Clostridioides difficile].}, journal = {La Revue du praticien}, volume = {69}, number = {7}, pages = {784-791}, pmid = {32233325}, issn = {2101-017X}, mesh = {*Clostridioides difficile/pathogenicity ; *Clostridium Infections ; Diarrhea ; France ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Interactions between intestinal microbiota and clostridioides difficile. Clostridioides difficile is a spore-forming anaerobic Gram-positive bacillus that is responsible for diarrhea and post-antibiotic colitis. Approximately 20,000 inpatients are infected by C. difficile in France per year. This bacterium is recognized as an emerging pathogen responsible for community-acquired diarrhea. Antibiotic therapy is the main risk factor for C. difficile infection (CDI) because it leads to intestinal dysbiosis and loss of "colonization resistance". C. difficile from endogenous or exogenous origin can then establish, multiply and produce its two toxins causing enterocyte lesions and a significant inflammatory reaction. The loss of colonization resistance has been associated with the loss of microbial diversity, particularly of some taxa that play a protective role. These variations of bacterial communities lead to changes in functions that can be explored by metabolomic or metagenomic approaches. Data from these experiments led to mechanistic assumptions about resistance or susceptibility to CDI. Microbiota studies have also pushed physicians to develop therapeutic approaches based on biotherapies. These therapies aim at repopulating the colon by a healthy microbiota either by fecal microbiota transplantation or by the administration of strains and cocktails of strains to restore the colonization resistance effect.}, }
@article {pmid32232453, year = {2020}, author = {Ransom, EM and Burnham, CD and Jones, L and Kraft, CS and McDonald, LC and Reinink, AR and Young, VB}, title = {Fecal Microbiota Transplantations: Where Are We, Where Are We Going, and What Is the Role of the Clinical Laboratory?.}, journal = {Clinical chemistry}, volume = {66}, number = {4}, pages = {512-517}, doi = {10.1093/clinchem/hvaa021}, pmid = {32232453}, issn = {1530-8561}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Clinical Laboratory Techniques/economics ; Clostridium Infections/microbiology/*therapy ; Donor Selection ; Expert Testimony ; Fecal Microbiota Transplantation/*adverse effects/economics/*methods ; Humans ; Transplantation, Homologous ; }, }
@article {pmid32231141, year = {2020}, author = {Vemuri, R and Shankar, EM and Chieppa, M and Eri, R and Kavanagh, K}, title = {Beyond Just Bacteria: Functional Biomes in the Gut Ecosystem Including Virome, Mycobiome, Archaeome and Helminths.}, journal = {Microorganisms}, volume = {8}, number = {4}, pages = {}, pmid = {32231141}, issn = {2076-2607}, abstract = {Gut microbiota refers to a complex network of microbes, which exerts a marked influence on the host's health. It is composed of bacteria, fungi, viruses, and helminths. Bacteria, or collectively, the bacteriome, comprises a significant proportion of the well-characterized microbiome. However, the other communities referred to as 'dark matter' of microbiomes such as viruses (virome), fungi (mycobiome), archaea (archaeome), and helminths have not been completely elucidated. Development of new and improved metagenomics methods has allowed the identification of complete genomes from the genetic material in the human gut, opening new perspectives on the understanding of the gut microbiome composition, their importance, and potential clinical applications. Here, we review the recent evidence on the viruses, fungi, archaea, and helminths found in the mammalian gut, detailing their interactions with the resident bacterial microbiota and the host, to explore the potential impact of the microbiome on host's health. The role of fecal virome transplantations, pre-, pro-, and syn-biotic interventions in modulating the microbiome and their related concerns are also discussed.}, }
@article {pmid32230987, year = {2020}, author = {Chong, CYL and Orr, D and Plank, LD and Vatanen, T and O'Sullivan, JM and Murphy, R}, title = {Randomised Double-Blind Placebo-Controlled Trial of Inulin with Metronidazole in Non-Alcoholic Fatty Liver Disease (NAFLD).}, journal = {Nutrients}, volume = {12}, number = {4}, pages = {}, pmid = {32230987}, issn = {2072-6643}, support = {A+ Trust//New Zealand Society for Gastroenterology/ ; }, mesh = {Adult ; Aged ; Alanine Transaminase/blood ; Anti-Infective Agents/*therapeutic use ; Caloric Restriction ; Double-Blind Method ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Inulin/*therapeutic use ; Male ; Metronidazole/*therapeutic use ; Middle Aged ; *Non-alcoholic Fatty Liver Disease/diet therapy/drug therapy ; Prebiotics ; Weight Loss ; Young Adult ; }, abstract = {Background: Non-alcoholic fatty liver disease (NAFLD) can be ameliorated by weight loss although difficult to maintain. Emerging evidence indicates that prebiotics and antibiotics improve NAFLD. Aim: To determine whether inulin supplementation after brief metronidazole therapy is effective in reducing alanine aminotransferase (ALT) and maintaining weight loss achieved through a very-low-calorie diet (VLCD) among people with NAFLD. Methods: Sixty-two people with NAFLD commenced 4-week VLCD using Optifast meal replacements (600 kcal/day). Sixty were then randomised into a 12-week double-blind, placebo-controlled, parallel three-arm trial: (1) 400 mg metronidazole twice daily in Week 1 then inulin 4 g twice daily OR (2) placebo twice daily in week one then inulin OR (3) placebo-placebo. Main outcomes were ALT and body weight at 12 weeks. Fecal microbiota changes were also evaluated. Results: Mean body mass index (BMI) and ALT reduced after VLCD by 2.4 kg/m[2] and 11 U/L, respectively. ALT further decreased after metronidazole-inulin compared to after placebo-placebo (mean ALT change -19.6 vs. -0.2 U/L, respectively; p = 0.026); however, weight loss maintenance did not differ. VLCD treatment decreased the ratio of Firmicutes/Bacteroidetes (p = 0.002). Conclusion: Brief metronidazole followed by inulin supplementation can reduce ALT beyond that achieved after VLCD in patients with NAFLD.}, }
@article {pmid32230951, year = {2020}, author = {Hiippala, K and Kainulainen, V and Suutarinen, M and Heini, T and Bowers, JR and Jasso-Selles, D and Lemmer, D and Valentine, M and Barnes, R and Engelthaler, DM and Satokari, R}, title = {Isolation of Anti-Inflammatory and Epithelium Reinforcing Bacteroides and Parabacteroides Spp. from A Healthy Fecal Donor.}, journal = {Nutrients}, volume = {12}, number = {4}, pages = {}, pmid = {32230951}, issn = {2072-6643}, support = {304490//Academy of Finland/ ; 323156//Academy of Finland/ ; 285632//Academy of Finland/ ; Reetta Satokari//Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6;/ ; }, mesh = {Adult ; Anti-Inflammatory Agents/*metabolism ; *Bacteroides/classification/immunology/isolation &amp; purification/metabolism ; Bacteroidetes/classification/immunology/isolation &amp; purification/metabolism ; Caco-2 Cells ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; High-Throughput Screening Assays ; Homeostasis/immunology ; Humans ; Interleukin-8/analysis/metabolism ; Lipopolysaccharides/metabolism ; Probiotics ; }, abstract = {Altered intestinal microbiota is associated with systemic and intestinal diseases, such as inflammatory bowel disease (IBD). Dysbiotic microbiota with enhanced proinflammatory capacity is characterized by depletion of anaerobic commensals, increased proportion of facultatively anaerobic bacteria, as well as reduced diversity and stability. In this study, we developed a high-throughput in vitro screening assay to isolate intestinal commensal bacteria with anti-inflammatory capacity from a healthy fecal microbiota transplantation donor. Freshly isolated gut bacteria were screened for their capacity to attenuate Escherichia coli lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) release from HT-29 cells. The screen yielded a number of Bacteroides and Parabacteroides isolates, which were identified as P. distasonis, B. caccae, B. intestinalis, B. uniformis, B. fragilis, B. vulgatus and B. ovatus using whole genome sequencing. We observed that a cell-cell contact with the epithelium was not necessary to alleviate in vitro inflammation as spent culture media from the isolates were also effective and the anti-inflammatory action did not correlate with the enterocyte adherence capacity of the isolates. The anti-inflammatory isolates also exerted enterocyte monolayer reinforcing action and lacked essential genes to synthetize hexa-acylated, proinflammatory lipid A, part of LPS. Yet, the anti-inflammatory effector molecules remain to be identified. The Bacteroides strains isolated and characterized in this study have potential to be used as so-called next-generation probiotics.}, }
@article {pmid32229549, year = {2020}, author = {Sullivan, MH and Boggiano, VL and Smith, KL}, title = {Management of difficult-to-treat Clostridioides difficile in a patient with chronic osteomyelitis.}, journal = {BMJ case reports}, volume = {13}, number = {3}, pages = {}, pmid = {32229549}, issn = {1757-790X}, mesh = {Administration, Intravenous ; Anti-Bacterial Agents/*adverse effects/*therapeutic use ; Clostridium Infections/*therapy ; Colitis/*microbiology/*therapy ; Combined Modality Therapy ; Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; Fidaxomicin/therapeutic use ; Foot/surgery ; Humans ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Osteomyelitis/*drug therapy ; Vancomycin/therapeutic use ; }, abstract = {A 61-year-old male patient being treated with intravenous antibiotics for left foot osteomyelitis presented to the hospital septic, with several days of worsening abdominal pain, bloating and watery bowel movements. Investigation revealed that the patient had severe, treatment-resistant Clostridioides difficile colitis. He was initially treated with oral vancomycin and intravenous metronidazole, which was switched to oral fidaxomicin. After no improvement in the patient's symptoms, he was treated with two faecal microbiota transplants. He was offered a third faecal microbiota transplant but declined. The patient was placed back on oral fidaxomicin and saw ultimate resolution of his symptoms. This case provides an example of a treatment pathway for refractory C. difficile infection.}, }
@article {pmid32228321, year = {2020}, author = {Morissette, A and Kropp, C and Songpadith, JP and Junges Moreira, R and Costa, J and Mariné-Casadó, R and Pilon, G and Varin, TV and Dudonné, S and Boutekrabt, L and St-Pierre, P and Levy, E and Roy, D and Desjardins, Y and Raymond, F and Houde, VP and Marette, A}, title = {Blueberry proanthocyanidins and anthocyanins improve metabolic health through a gut microbiota-dependent mechanism in diet-induced obese mice.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {318}, number = {6}, pages = {E965-E980}, doi = {10.1152/ajpendo.00560.2019}, pmid = {32228321}, issn = {1522-1555}, support = {//CIHR/Canada ; }, mesh = {Animals ; Anthocyanins/*pharmacology ; *Blueberry Plants ; Body Weight/drug effects ; Diet, High-Fat ; Dietary Sucrose ; Fecal Microbiota Transplantation ; *Fruit ; Gastrointestinal Microbiome/*drug effects ; Glucose Tolerance Test ; *Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/*metabolism/microbiology ; Plant Extracts/*pharmacology ; Proanthocyanidins/*pharmacology ; }, abstract = {Blueberry consumption can prevent obesity-linked metabolic diseases, and it has been proposed that the polyphenol content of blueberries may contribute to these effects. Polyphenols have been shown to favorably impact metabolic health, but the role of specific polyphenol classes and whether the gut microbiota is linked to these effects remain unclear. We aimed to evaluate the impact of whole blueberry powder and blueberry polyphenols on the development of obesity and insulin resistance and to determine the potential role of gut microbes in these effects by using fecal microbiota transplantation (FMT). Sixty-eight C57BL/6 male mice were assigned to one of the following diets for 12 wk: balanced diet (Chow); high-fat, high-sucrose diet (HFHS); or HFHS supplemented with whole blueberry powder (BB), anthocyanidin (ANT)-rich extract, or proanthocyanidin (PAC)-rich extract. After 8 wk, mice were housed in metabolic cages, and an oral glucose tolerance test (OGTT) was performed. Sixty germ-free mice fed HFHS diet received FMT from one of the above groups biweekly for 8 wk, followed by an OGTT. PAC-treated mice were leaner than HFHS controls although they had the same energy intake and were more physically active. This observation was reproduced in germ-free mice receiving FMT from PAC-treated mice. PAC- and ANT-treated mice showed improved insulin responses during OGTT, and this finding was also reproduced in germ-free mice following FMT. These results show that blueberry PAC and ANT polyphenols can reduce diet-induced body weight and improve insulin sensitivity and that at least part of these beneficial effects are explained by modulation of the gut microbiota.}, }
@article {pmid32228039, year = {2020}, author = {Hinton, R}, title = {A case report looking at the effects of faecal microbiota transplantation in a patient with bipolar disorder.}, journal = {The Australian and New Zealand journal of psychiatry}, volume = {54}, number = {6}, pages = {649-650}, doi = {10.1177/0004867420912834}, pmid = {32228039}, issn = {1440-1614}, mesh = {*Bipolar Disorder ; Depression ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid32222124, year = {2020}, author = {Dale, HF and Lied, GA}, title = {Gut microbiota and therapeutic approaches for dysbiosis in irritable bowel syndrome: recent developments and future perspectives.}, journal = {Turkish journal of medical sciences}, volume = {50}, number = {SI-2}, pages = {1632-1641}, pmid = {32222124}, issn = {1303-6165}, mesh = {*Dysbiosis/microbiology/physiopathology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/microbiology/physiopathology/therapy ; Probiotics ; }, abstract = {Increased knowledge regarding the implications of gut microbiota in irritable bowel syndrome (IBS) suggests that a disturbed intestinal microenvironment (dysbiosis) might promote the development and maintenance of IBS symptoms and affects several pathways in the pathology of this multifactorial disease. Accordingly, manipulation of the gut microbiota in order to improve IBS symptoms has evolved as a novel treatment strategy in the last decade. Several different approaches have been investigated in order to improve the gut microbiota composition. Dietary modifications including supplementation with fibers, prebiotics, and probiotics are shown to improve symptoms and composition of gut microbiota in IBS; however, the exact probiotic mixture beneficial for each individual remains to be identified. The use of antibiotics still needs confirmation, although promising results have been reported with use of rifaximin. Fecal microbiota transplantation (FMT) has recently gained a lot of attention, and several placebo-controlled trials investigating FMT obtain promising results regarding symptom reduction and gut microbiota manipulation in IBS. However, more data regarding long-term effects are needed before FMT can be integrated as a customized treatment for IBS in the clinical routine.}, }
@article {pmid32218321, year = {2020}, author = {Polimeno, L and Barone, M and Mosca, A and Viggiani, MT and Joukar, F and Mansour-Ghanaei, F and Mavaddati, S and Daniele, A and Debellis, L and Bilancia, M and Santacroce, L and Di Leo, A}, title = {Soy Metabolism by Gut Microbiota from Patients with Precancerous Intestinal Lesions.}, journal = {Microorganisms}, volume = {8}, number = {4}, pages = {}, pmid = {32218321}, issn = {2076-2607}, support = {PON-BIOMIS 2018 (Project: Costituzione della Biobanca del Microbiota intestinale e salivare umano: dalla disbiosi alla simbiosi).//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca/ ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) requires the presence of a variety of factors predisposing a tumorigenic milieu. Excluding familial clustering and hereditary CRC syndromes, the development of sporadic CRC from precancerous lesions is influenced by tissue inflammation, modulation of intestinal immunity, hormones, dietary habits and gut microbiota composition. As concerning the last two aspects, the intestinal presence of equol, the most biologically active metabolite of the soy isoflavone daidzein and the presence of a genetic determinant of gut microbiota able to metabolize daidzein, seem to lower the CRC risk. It has been hypothesized that the anaerobic microorganisms of the Bacteroides genus play a role in equol production.<br><br>AIM: To evaluate the presence of (i) anaerobic gut microbiota and (ii) the urinary levels of soy isoflavones (daidzein, genistein and equol) in patients with and without precancerous lesions, challenged with a daidzein-rich soy extract.<br><br>METHODS: Consecutive subjects undergoing colonoscopy participated to the study. Feces were collected from all patients one week before colonoscopy for gut microbiota studies. After the endoscopy examination and the histological evaluation, 40 subjects, 20 with sporadic colorectal adenomas (SCA/P group) and 20 without proliferative lesions (control group) were enrolled for the study. Urine levels of soy isoflavones daidzein, genistein and their metabolite equol, were determined by high performance liquid chromatographic (HPLC) analysis and gut microbiota analysis was performed by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) procedure.<br><br>RESULTS: Seventeen different bacterial species were identified in the fecal samples of the forty subjects participating to the study. Ten bacterial species resulted anaerobic Gram-negative bacteria, all belonging to the Bacteroides genus. A significant difference of bacteria species was evidenced in the fecal samples of the two groups of subjects. Particularly important was the evidence of Parabacteroides distasonis, Clostridium clostridioforme and Pediococcus pentasaceus only in control fecal samples, such as the presence of Bacteroides fragilis and Prevotella melaningenica only in SCA/P fecal samples. Concerning the soy isoflavones levels, no statistically significant differences were revealed in the genistein and daidzein urinary levels between the two groups of subjects. On the contrary, urinary equol levels were undetectable in ten SCA/P subjects and in two controls; moreover, when present, the levels of urinary equol were significantly lower in SCA/P subjects compared to controls (0.24 &#xb1; 0.27 mg/24 hrs vs. 21.25 &#xb1; 4.3 mg/24 hrs, respectively, p = 1.12 &#xd7; 10[-6]).<br><br>CONCLUSIONS: Our results suggest that the presence of anaerobic Bacteroides in the colon, and the production of equol from soy, could determine a milieu able to contrast the development of colonic mucosa proliferative lesions.}, }
@article {pmid32217945, year = {2021}, author = {Logre, E and Bert, F and Khoy-Ear, L and Janny, S and Giabicani, M and Grigoresco, B and Toussaint, A and Dondero, F and Dokmak, S and Roux, O and Francoz, C and Soubrane, O and Durand, F and Paugam-Burtz, C and Weiss, E}, title = {Risk Factors and Impact of Perioperative Prophylaxis on the Risk of Extended-spectrum β-Lactamase-producing Enterobacteriaceae-related Infection Among Carriers Following Liver Transplantation.}, journal = {Transplantation}, volume = {105}, number = {2}, pages = {338-345}, doi = {10.1097/TP.0000000000003231}, pmid = {32217945}, issn = {1534-6080}, mesh = {Anti-Bacterial Agents/*administration &amp; dosage/adverse effects ; *Antibiotic Prophylaxis ; Carbapenems/*administration &amp; dosage/adverse effects ; *Carrier State ; Databases, Factual ; Enterobacteriaceae Infections/diagnosis/microbiology/*prevention &amp; control ; Feces/*microbiology ; Female ; Humans ; Liver Transplantation/*adverse effects ; Male ; Middle Aged ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) carriage is frequent among liver transplant (LT) recipients, thereby fostering a large empirical carbapenem prescription. However, ESBL-E infections occur in only 10%-25% of critically ill patients with rectal colonization. Our aim was to identify risk factors for post-LT ESBL-E infection in colonized patients. The effect of perioperative antimicrobial prophylaxis (AP) was also analyzed in patients with prophylaxis lasting <48 hours and without proven intraoperative infection.<br><br>METHODS: Retrospective study from a prospective database including patients with a positive ESBL-E rectal screening transplanted between 2010 and 2016.<br><br>RESULTS: Among the 749 patients transplanted, 100 (13.3%) were colonized with an ESBL-E strain. Thirty-nine (39%) patients developed an infection related to the same ESBL-E (10 pulmonary, 11 surgical site, 13 urinary, 5 bloodstream) within 11 postoperative days in median. Klebsiella pneumoniae carriage, model for end-stage liver disease &#x2265;25, preoperative spontaneous bacterial peritonitis prophylaxis, and antimicrobial exposure during the previous month were independent predictors of ESBL-E infection. We propose a colonization to infection risk score built on these variables. The prevalence of infection for colonization to infection score of 0, 1, 2, and &#x2265;3 were 7.4%, 26.3%, 61.9%, and 91.3%, respectively. Of note, the incidence of post-LT ESBL-E infection was lower in case of perioperative AP targeting colonizing ESBL-E (P = 0.04).<br><br>CONCLUSIONS: Thirty-nine percentage of ESBL-E carriers develop a related infection after LT. We identified predictors for ESBL-E infection in carriers that may help in rationalizing carbapenem prescription. Perioperative AP targeting colonizing ESBL-E may be associated with a reduced risk of post-LT ESBL-E infections.}, }
@article {pmid32216675, year = {2020}, author = {Xiaoyu, P and Chao, G and Lihua, D and Pengyu, C}, title = {Gut bacteria affect the tumoral immune milieu: distorting the efficacy of immunotherapy or not？.}, journal = {Gut microbes}, volume = {11}, number = {4}, pages = {691-705}, pmid = {32216675}, issn = {1949-0984}, mesh = {Animals ; Bacteria ; *Bacterial Physiological Phenomena ; Biomarkers ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Immunity ; *Immunotherapy ; Neoplasms/*immunology/*therapy ; Symbiosis ; }, abstract = {Immunotherapy using immune-checkpoint inhibitors is revolutionizing oncotherapy. However, the application of immunotherapy may be restricted because of the lack of proper biomarkers in a portion of cancer patients. Recently, emerging evidence has revealed that gut commensal bacteria can impact the therapeutic efficacy of immune-checkpoint inhibitors in several cancer models. In addition, testing the composition of gut bacteria provides context for prediction of the efficacy and toxicity of immunotherapy. In this review, we discuss the impacts of gut commensal bacteria on the tumoral immune milieu, highlighting some typical bacteria and their associations with immunotherapy.}, }
@article {pmid32215122, year = {2020}, author = {Kukla, M and Adrych, K and Dobrowolska, A and Mach, T and Reguła, J and Rydzewska, G}, title = {Guidelines for Clostridium difficile infection in adults.}, journal = {Przeglad gastroenterologiczny}, volume = {15}, number = {1}, pages = {1-21}, pmid = {32215122}, issn = {1895-5770}, abstract = {Clostridium difficile infection (CDI) has become a serious medical and epidemiological problem, especially in well developed countries. There has been evident increase in incidence and severity of CDI. Prevention, proper diagnosis and effective treatment are necessary to reduce the risk for the patients, deplete the spreading of infection and diminish the probability of recurrent infection. Antibiotics are the fundamental treatment of CDI. In patients who had recurrent CDI fecal microbiota transplantation seems to be promising and efficient strategy. These guidelines systematize existing data and include recent changes implemented in the management of CDI.}, }
@article {pmid32214138, year = {2020}, author = {Kummen, M and Solberg, OG and Storm-Larsen, C and Holm, K and Ragnarsson, A and Trøseid, M and Vestad, B and Skårdal, R and Yndestad, A and Ueland, T and Svardal, A and Berge, RK and Seljeflot, I and Gullestad, L and Karlsen, TH and Aaberge, L and Aukrust, P and Hov, JR}, title = {Rosuvastatin alters the genetic composition of the human gut microbiome.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {5397}, pmid = {32214138}, issn = {2045-2322}, support = {2016067//Helse S&#xf8;r-&#xf8;st RHF/International ; 240787/F20//Norges Forskningsr&#xe5;d/International ; }, mesh = {Adult ; Aged ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/*genetics/physiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Microbiota/drug effects/genetics ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Rosuvastatin Calcium/metabolism/*pharmacology ; }, abstract = {The gut microbiome contributes to the variation of blood lipid levels, and secondary bile acids are associated with the effect of statins. Yet, our knowledge of how statins, one of our most common drug groups, affect the human microbiome is scarce. We aimed to characterize the effect of rosuvastatin on gut microbiome composition and inferred genetic content in stool samples from a randomized controlled trial (n = 66). No taxa were significantly altered by rosuvastatin during the study. However, rosuvastatin-treated participants showed a reduction in the collective genetic potential to transport and metabolize precursors of the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO, p < 0.01), and an increase of related metabolites betaine and γ-butyrobetaine in plasma (p < 0.01). Exploratory analyses in the rosuvastatin group showed that participants with the least favorable treatment response (defined as < median change in high-density/low-density lipoprotein (HDL/LDL) ratio) showed a marked increase in TMAO-levels compared to those with a more favorable response (p < 0.05). Our data suggest that while rosuvastatin has a limited effect on gut microbiome composition, it could exert broader collective effects on the microbiome relevant to their function, providing a rationale for further studies of the influence of statins on the gut microbiome.}, }
@article {pmid32213039, year = {2020}, author = {Keller, JJ and Vehreschild, MJ and Hvas, CL and Jørgensen, SM and Kupcinskas, J and Link, A and Mulder, CJ and Goldenberg, SD and Arasaradnam, R and Sokol, H and Gasbarrini, A and Hoegenauer, C and Terveer, EM and Kuijper, EJ and Arkkila, P}, title = {Donated stool for faecal microbiota transplantation is not a drug, but guidance and regulation are needed.}, journal = {United European gastroenterology journal}, volume = {8}, number = {3}, pages = {353-354}, doi = {10.1177/2050640620910847}, pmid = {32213039}, issn = {2050-6414}, support = {PB-PG-0418-20007/DH_/Department of Health/United Kingdom ; }, mesh = {*Clostridioides difficile ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Pharmaceutical Preparations ; }, }
@article {pmid32207794, year = {2020}, author = {Slomski, A}, title = {"Superdonor" Fecal Microbiota Transplant Effective for IBS.}, journal = {JAMA}, volume = {323}, number = {12}, pages = {1124}, doi = {10.1001/jama.2020.2812}, pmid = {32207794}, issn = {1538-3598}, }
@article {pmid32205337, year = {2020}, author = {Huang, Z and Chen, J and Li, B and Zeng, B and Chou, CH and Zheng, X and Xie, J and Li, H and Hao, Y and Chen, G and Pei, F and Shen, B and Kraus, VB and Wei, H and Zhou, X and Cheng, L}, title = {Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice.}, journal = {Annals of the rheumatic diseases}, volume = {79}, number = {5}, pages = {646-656}, pmid = {32205337}, issn = {1468-2060}, support = {P30 AG028716/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Biomarkers/analysis ; Biopsy, Needle ; Disease Models, Animal ; Disease Progression ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Menisci, Tibial/pathology/surgery ; Metabolic Syndrome/*complications/pathology ; Mice, Inbred C57BL ; Multivariate Analysis ; Osteoarthritis, Knee/pathology/*therapy ; Random Allocation ; Reference Values ; Regression Analysis ; Risk Assessment ; }, abstract = {OBJECTIVES: Emerging evidence suggests that the microbiome plays an important role in the pathogenesis of osteoarthritis (OA). We aimed to test the two-hit model of OA pathogenesis and potentiation in which one 'hit' is provided by an adverse gut microbiome that activates innate immunity; the other 'hit' is underlying joint damage.<br><br>METHODS: Medical history, faecal and blood samples were collected from human healthy controls (OA-METS-, n=4), knee OA without metabolic syndrome (OA+METS-, n=7) and knee OA with metabolic syndrome (OA+METS+, n=9). Each group of human faecal samples, whose microbial composition was identified by 16S rRNA sequencing, was pooled and transplanted into germ-free mice 2 weeks prior to meniscal/ligamentous injury (MLI) (n&#x2265;6 per group). Eight weeks after MLI, mice were evaluated for histological OA severity and synovitis, systemic inflammation and gut permeability.<br><br>RESULTS: Histological OA severity following MLI was minimal in germ-free mice. Compared with the other groups, transplantation with the OA+METS+ microbiome was associated with higher mean systemic concentrations of inflammatory biomarkers (interleukin-1&#x3b2;, interleukin-6 and macrophage inflammatory protein-1&#x3b1;), higher gut permeability and worse OA severity. A greater abundance of Fusobacterium and Faecalibaterium and lesser abundance of Ruminococcaceae in transplanted mice were consistently correlated with OA severity and systemic biomarkers concentrations.<br><br>CONCLUSION: The study clearly establishes a direct gut microbiome-OA connection that sets the stage for a new means of exploring OA pathogenesis and potentially new OA therapeutics. Alterations of Fusobacterium, Faecalibaterium and Ruminococcaceae suggest a role of these particular microbes in exacerbating OA.}, }
@article {pmid32205168, year = {2020}, author = {Young, E and Nolan, J and Argyrides, J}, title = {An Unexpected Cause of Gastrointestinal Bleeding after Stem Cell Transplantation.}, journal = {Gastroenterology}, volume = {159}, number = {2}, pages = {443-445}, doi = {10.1053/j.gastro.2020.03.035}, pmid = {32205168}, issn = {1528-0012}, mesh = {Computed Tomography Angiography ; Endoscopy, Gastrointestinal ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Jejunal Diseases/*diagnosis/etiology/pathology/surgery ; Jejunum/diagnostic imaging/pathology/surgery ; Lymphoproliferative Disorders/*diagnosis/etiology/pathology/surgery ; Male ; Melena/*etiology/surgery ; Middle Aged ; Primary Myelofibrosis/*therapy ; }, }
@article {pmid32204538, year = {2020}, author = {Tsai, MC and Liu, YY and Lin, CC and Wang, CC and Wu, YJ and Yong, CC and Chen, KD and Chuah, SK and Yao, CC and Huang, PY and Chen, CH and Hu, TH and Chen, CL}, title = {Gut Microbiota Dysbiosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study in Taiwan.}, journal = {Nutrients}, volume = {12}, number = {3}, pages = {}, pmid = {32204538}, issn = {2072-6643}, support = {CMRPG8H1111//Kaohsiung Chang Gung Memorial Hospital/ ; CMRPG8J1571//Kaohsiung Chang Gung Memorial Hospital/ ; CMRPG8K0661//Kaohsiung Chang Gung Memorial Hospital/ ; }, mesh = {Adolescent ; Adult ; Aged ; Biomarkers ; Biopsy ; Case-Control Studies ; Cross-Sectional Studies ; *Dysbiosis ; Female ; *Gastrointestinal Microbiome ; Humans ; Liver/metabolism/pathology ; Male ; Metagenome ; Metagenomics/methods ; Middle Aged ; Non-alcoholic Fatty Liver Disease/diagnosis/*epidemiology/*etiology ; Public Health Surveillance ; Taiwan/epidemiology ; Young Adult ; }, abstract = {The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus Ruminococcaceae UCG-010, family Ruminococcaceae, order Clostridiales, and class Clostridia were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes. These results are different from research from western countries and could provide different targets for therapies by region.}, }
@article {pmid32203111, year = {2020}, author = {Hui, S and Liu, Y and Huang, L and Zheng, L and Zhou, M and Lang, H and Wang, X and Yi, L and Mi, M}, title = {Resveratrol enhances brown adipose tissue activity and white adipose tissue browning in part by regulating bile acid metabolism via gut microbiota remodeling.}, journal = {International journal of obesity (2005)}, volume = {44}, number = {8}, pages = {1678-1690}, pmid = {32203111}, issn = {1476-5497}, mesh = {Adipose Tissue, Brown/*physiology ; Adipose Tissue, White/*physiology ; Animals ; Bile Acids and Salts/*metabolism ; Body Weight ; *Gastrointestinal Microbiome ; Glucose/metabolism ; Homeostasis ; Male ; Mice ; Mice, Inbred Strains ; Receptors, G-Protein-Coupled/metabolism ; Resveratrol/*pharmacology ; Uncoupling Protein 1/metabolism ; }, abstract = {OBJECTIVE: Current evidence has linked dietary resveratrol (RSV) intake to the activation of brown adipose tissue (BAT) and induction of white adipose tissue (WAT) browning, which may be a potential means of improving glucose homeostasis. However, the underlying mechanisms remain unclear.<br><br>METHODS: A diet containing RSV was fed to db/db mice for 10 weeks, following which the body weight, adipose tissue accumulation, bile acid (BA) profiles, and markers of BA metabolism were analyzed. Oral glucose tolerance testing, immunohistochemistry, and gut microbiota sequencing were also performed.<br><br>RESULTS: RSV intervention improved glucose homeostasis in db/db mice, which was linked to the enhanced BAT activity and WAT browning. Moreover, RSV-treated mice exhibited altered plasma and fecal BA compositions and significant remodeling of the gut microbiota, the latter confirmed by a higher level of lithocholic acid (LCA) in the plasma and feces. LCA was identified to be the agonist of Takeda G-protein coupled receptor 5 (TGR5), which mediated the BAT activation and WAT browning by upregulating uncoupling protein 1 (UCP1) expression. Furthermore, depletion of the gut microbiota using antibiotics partially abolished the beneficial effects of RSV against glucose intolerance. Finally, microbiota transplantation experiments demonstrated that the RSV-induced beneficial effects were transferable, indicating that these effects were largely dependent on the gut microbiota.<br><br>CONCLUSIONS: These data indicate that RSV administration improves glucose homeostasis by enhancing BAT activation and WAT browning, a mechanism that might partially be mediated by the gut microbiota-BA-TGR5/UCP1 pathway.}, }
@article {pmid32200611, year = {2020}, author = {Zybura, J and Dyla, A and Mielnicki, W}, title = {Fecal microbiota transplantation is feasible even in critically ill patients with toxic megacolon due to Clostridium difficile infection.}, journal = {Anaesthesiology intensive therapy}, volume = {52}, number = {2}, pages = {177-180}, pmid = {32200611}, issn = {1731-2531}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/complications/*therapy ; Critical Illness ; Feasibility Studies ; *Fecal Microbiota Transplantation ; Humans ; Male ; Megacolon, Toxic/*etiology ; }, }
@article {pmid32197802, year = {2020}, author = {Khoruts, A and Bajaj, JS}, title = {Reply to: " 'You know my name, but not my story' - Deciding on an accurate nomenclature for faecal microbiota transplantation": Intestinal microbiota transplantation: Naming a new paradigm.}, journal = {Journal of hepatology}, volume = {72}, number = {6}, pages = {1213-1214}, doi = {10.1016/j.jhep.2020.02.014}, pmid = {32197802}, issn = {1600-0641}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis ; *Liver Diseases ; *Microbiota ; }, }
@article {pmid32197801, year = {2020}, author = {Philips, CA and Ahamed, R and Rajesh, S and Augustine, P}, title = {'You know my name, but not my story' - Deciding on an accurate nomenclature for faecal microbiota transplantation.}, journal = {Journal of hepatology}, volume = {72}, number = {6}, pages = {1212-1213}, doi = {10.1016/j.jhep.2020.02.004}, pmid = {32197801}, issn = {1600-0641}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis ; *Liver Diseases ; *Microbiota ; }, }
@article {pmid32196881, year = {2020}, author = {Ford, CD and Lopansri, BK and Coombs, J and Webb, BJ and Asch, J and Hoda, D}, title = {Are Clostridioides difficile infections being overdiagnosed in hematopoietic stem cell transplant recipients?.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {22}, number = {4}, pages = {e13279}, doi = {10.1111/tid.13279}, pmid = {32196881}, issn = {1399-3062}, support = {//Hemingway Cancer Research Fund/ ; 784//Intermountain Healthcare Medical and Research Foundation/ ; }, mesh = {Adult ; Aged ; Clostridioides difficile/classification/*isolation &amp; purification ; Clostridium Infections/*diagnosis/*epidemiology ; Diagnostic Errors/*statistics &amp; numerical data ; Diarrhea/etiology/microbiology ; False Positive Reactions ; Feces/*microbiology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Ribotyping ; Young Adult ; }, abstract = {BACKGROUND: Because both diarrhea due to other causes and gastrointestinal colonization with toxigenic Clostridioides difficile are common in HSCT, there is a possibility of false-positive diagnoses of C difficile infections (CDI).<br><br>METHODS: We estimated the probability of a patient being colonized by toxigenic C&#xa0;difficile by testing non-diarrheal surveillance stools from 223 HSCT recipients and the probability that a specimen submitted for C&#xa0;difficile testing was not CDI by determining the number of clinical tests that returned negative from this cohort. The number of expected false-positive CDI was estimated using these probabilities and compared with observed clinical test results.<br><br>RESULTS: The expected false-positive and the observed numbers of positive clinical results were similar. The 20 patients diagnosed with CDI were also similar to 142 patients with diarrhea and C&#xa0;difficile-negative stools in number of stools on day of testing, associated symptoms, and the recorded number of days to formed stools. C&#xa0;difficile colonization was most commonly detected during the first week and CDI during the second. Retrospective analysis of 837 patients showed that 18 stools were submitted for each diagnosis of CDI. Ribotyping of the surveillance samples showed 17 ribotypes.<br><br>CONCLUSIONS: Although several assumptions could impact the accuracy of our false-positive CDI estimates, it appears that many HSCT recipients diagnosed with CDI may actually represent colonized status and an alternative cause of diarrhea. Diagnostic stewardship, including limiting CDI diagnoses to patients with positive toxin and restricting stool submissions to patients with more severe symptoms, may decrease the number of false-positive diagnoses.}, }
@article {pmid32194836, year = {2020}, author = {Hu, ZB and Lu, J and Chen, PP and Lu, CC and Zhang, JX and Li, XQ and Yuan, BY and Huang, SJ and Ruan, XZ and Liu, BC and Ma, KL}, title = {Dysbiosis of intestinal microbiota mediates tubulointerstitial injury in diabetic nephropathy via the disruption of cholesterol homeostasis.}, journal = {Theranostics}, volume = {10}, number = {6}, pages = {2803-2816}, pmid = {32194836}, issn = {1838-7640}, mesh = {Acetates/blood ; Animals ; Cell Line ; Cholesterol/*metabolism ; *Diabetic Nephropathies/metabolism/microbiology ; *Dysbiosis/metabolism/microbiology ; *Gastrointestinal Microbiome ; Homeostasis ; Humans ; Male ; *Nephritis, Interstitial/metabolism/microbiology ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled/metabolism ; }, abstract = {Background: Our previous study demonstrated that the disruption of cholesterol homeostasis promotes tubulointerstitial injury in diabetic nephropathy (DN). This study aimed to further investigate the effects of gut microbiota dysbiosis on this process and explored its potential mechanism. Methods: Diabetic rats treated with broad-spectrum oral antibiotics or faecal microbiota transplantation (FMT) from the healthy donor group and human kidney 2 (HK-2) cells stimulated with sodium acetate were used to observe the effects of gut microbiota on cholesterol homeostasis. The gut microbiota distribution was measured by 16S rDNA sequencing with faeces. Serum acetate level was examined by gas chromatographic analysis. Protein expression of G protein coupled receptor 43 (GPR43) and molecules involved in cholesterol homeostasis were assessed by immunohistochemical staining, immunofluorescence staining, and Western Blotting. Results: Depletion of gut microbiota significantly attenuated albuminuria and tubulointerstitial injury. Interestingly, serum acetate levels were also markedly decreased in antibiotics-treated diabetic rats and positively correlated with the cholesterol contents in kidneys. An in vitro study demonstrated that acetate significantly increased cholesterol accumulation in HK-2 cells, which was caused by increased expression of proteins mainly modulating cholesterol synthesis and uptake. As expected, FMT effectively decreased serum acetate levels and alleviated tubulointerstitial injury in diabetic rats through overriding the disruption of cholesterol homeostasis. Furthermore, GPR43 siRNA treatment blocked acetate-mediated cholesterol homeostasis dysregulation in HK-2 cells through decreasing the expression of proteins governed cholesterol synthesis and uptake. Conclusion: Our studies for the first time demonstrated that the acetate produced from gut microbiota mediated the dysregulation of cholesterol homeostasis through the activation of GPR43, thereby contributing to the tubulointerstitial injury of DN, suggesting that gut microbiota reprogramming might be a new strategy for DN prevention and therapy.}, }
@article {pmid32193686, year = {2020}, author = {Okamoto, T and Hatakeyama, S and Imai, A and Yamamoto, H and Yoneyama, T and Mori, K and Yoneyama, T and Hashimoto, Y and Nakaji, S and Ohyama, C}, title = {The association between gut microbiome and erectile dysfunction: a community-based cross-sectional study in Japan.}, journal = {International urology and nephrology}, volume = {52}, number = {8}, pages = {1421-1428}, doi = {10.1007/s11255-020-02443-9}, pmid = {32193686}, issn = {1573-2584}, support = {18K16717//the Japan Society for the Promotion of Science/ ; 18K16718//the Japan Society for the Promotion of Science/ ; }, mesh = {Adult ; Aged ; Cross-Sectional Studies ; Erectile Dysfunction/*epidemiology ; *Gastrointestinal Microbiome ; Humans ; Japan ; Male ; Middle Aged ; }, abstract = {PURPOSE: We investigated the gut microbiome in subjects with erectile dysfunction (ED) in a community-based population.<br><br>METHODS: This cross-sectional study surveyed comprehensive health status in 408 men who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. The gut microbiome was assessed by tag sequencing of the 16S rRNA gene, which we extracted from fecal samples. Erectile function was evaluated with the five-item International Index of Erectile Function (IIEF-5), and the men were divided into two groups: low-IIEF-5 (&#x2264;&#x2009;16) and high-IIEF-5 (>&#x2009;16). Of those, we selected age-adjusted 192 men (96 each) for analysis. We investigated the association of gut microbiome with IIEF-5 between the two groups.<br><br>RESULTS: Median age was 50&#xa0;years. No significant difference was seen in the history of hypertension, DM, CKD, and CVD between the low-IIEF-5 and high-IIEF-5 groups. However, the relative abundance of Alistipes (related with anti-inflammation) and Clostoridium XVIII (related with bowel movement) was significantly different between the two groups. Multivariate logistic analysis demonstrated that the relative abundance of Clostridium XVIII (OR, 2.06; 95% CI, 1.20-3.55, P&#xa0;=&#xa0;0.009) and Alistipes (OR, 0.81; 95% CI, 0.66-0.99, P&#xa0;=&#xa0;0.040) and, with an IPSS&#xa0;&#x2265;&#xa0;8, were independent factors for low IIEF-5.<br><br>CONCLUSION: We observed significant association between the low-IIEF-5 and high-IIEF-5 groups in Alistipes and Clostoridium XVIII. Further study is necessary to access the causal relationship between the gut microbiome and ED.}, }
@article {pmid32192627, year = {2020}, author = {Ianiro, G and Mullish, BH and Kelly, CR and Sokol, H and Kassam, Z and Ng, SC and Fischer, M and Allegretti, JR and Masucci, L and Zhang, F and Keller, J and Sanguinetti, M and Costello, SP and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {Screening of faecal microbiota transplant donors during the COVID-19 outbreak: suggestions for urgent updates from an international expert panel.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {5}, number = {5}, pages = {430-432}, pmid = {32192627}, issn = {2468-1253}, mesh = {Betacoronavirus/*isolation &amp; purification ; COVID-19 ; Coronavirus Infections/epidemiology/*virology ; Fecal Microbiota Transplantation/*methods/standards ; Feces/microbiology/virology ; Humans ; Living Donors ; Mass Screening/methods ; Pandemics ; Pneumonia, Viral/epidemiology/*virology ; SARS-CoV-2 ; }, }
@article {pmid32192415, year = {2020}, author = {Tomlinson, JE and Jager, M and Struzyna, A and Laverack, M and Fortier, LA and Dubovi, E and Foil, LD and Burbelo, PD and Divers, TJ and Van de Walle, GR}, title = {Tropism, pathology, and transmission of equine parvovirus-hepatitis.}, journal = {Emerging microbes &amp; infections}, volume = {9}, number = {1}, pages = {651-663}, pmid = {32192415}, issn = {2222-1751}, support = {K08 AI141767/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Diptera/virology ; Feces/virology ; Female ; Hepatitis, Viral, Animal/pathology/transmission/*virology ; Hepatocytes/pathology/virology ; Horse Diseases/pathology/transmission/*virology ; Horses ; Infectious Disease Transmission, Vertical ; Insect Vectors/virology ; Liver/pathology/*virology ; Lymphocytes ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/virology ; Mouth/virology ; Necrosis ; Parvoviridae Infections/pathology/transmission/*veterinary/virology ; Parvovirus/isolation &amp; purification/pathogenicity/*physiology ; Viral Tropism ; Viremia ; Virus Shedding ; }, abstract = {Equine parvovirus-hepatitis (EqPV-H) has recently been associated with cases of Theiler's disease, a form of fulminant hepatic necrosis in horses. To assess whether EqPV-H is the cause of Theiler's disease, we first demonstrated hepatotropism by PCR on tissues from acutely infected horses. We then experimentally inoculated horses with EqPV-H and 8 of 10 horses developed hepatitis. One horse showed clinical signs of liver failure. The onset of hepatitis was temporally associated with seroconversion and a decline in viremia. Liver histology and in situ hybridization showed lymphocytic infiltrates and necrotic EqPV-H-infected hepatocytes. We next investigated potential modes of transmission. Iatrogenic transmission via allogeneic stem cell therapy for orthopedic injuries was previously suggested in a case series of Theiler's disease, and was demonstrated here for the first time. Vertical transmission and mechanical vectoring by horse fly bites could not be demonstrated in this study, potentially due to limited sample size. We found EqPV-H shedding in oral and nasal secretions, and in feces. Importantly, we could demonstrate EqPV-H transmission via oral inoculation with viremic serum. Together, our findings provide additional information that EqPV-H is the likely cause of Theiler's disease and that transmission of EqPV-H occurs via both iatrogenic and natural routes.}, }
@article {pmid32190126, year = {2020}, author = {Coil, DA and Jospin, G and Eisen, JA}, title = {Draft Genome Analysis of Christensenella minuta DSM 22607, exhibiting an unusual expansion of transporter homologs of unknown function.}, journal = {Journal of genomics}, volume = {8}, number = {}, pages = {25-29}, pmid = {32190126}, issn = {1839-9940}, abstract = {Christensenella minuta was first formally described in 2012 as a member of a novel species, genus, and proposed family of Christensenellaceae. C. minuta was later shown in one study to be part of the most heritable taxonomic group in the human gut microbiome and to be enriched in people with low body mass index (BMI). Mouse work demonstrated that injection of cultured C. minuta into germ-free mice prevented the onset of obesity after a fecal transplant to the mice from high BMI individuals. Here we describe the genome sequence of C. minuta DSM 22607. Examination and analysis of the annotation revealed an unusually high number of genes predicted to be involved in carbohydrate metabolism, many of which were multiple homologs of RbsA, RbsB and RbsC, which together make up the Ribose ABC Transport System. These genes may be also involved in quorum sensing which could potentially relate to the importance of C. minuta in the gut microbiome.}, }
@article {pmid32189422, year = {2020}, author = {Hamilton, LA and Behal, ML}, title = {Altering Routine Intensive Care Unit Practices to Support Commensalism.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {35}, number = {3}, pages = {433-441}, doi = {10.1002/ncp.10484}, pmid = {32189422}, issn = {1941-2452}, mesh = {Analgesics, Opioid ; Anti-Bacterial Agents ; Critical Care/*methods ; Critical Illness/*therapy ; Decontamination/methods ; Enteral Nutrition/methods ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Immune System/drug effects/microbiology/physiology ; Intensive Care Units ; Parenteral Nutrition/methods ; Proton Pump Inhibitors ; }, abstract = {The gastrointestinal (GI) tract consists of trillions of organisms that support multiple functions in the body, from immunity, digestion, and absorption to drug metabolism. These microbes form an overall collection of microorganisms that form the body's microbiome. In critical illness, many of these functions are aberrant, and the microbiome is altered, leading to untoward effects. Some of the most common medications received by patients include antibiotics and proton pump inhibitors, which affect particular changes in the microbiome. In addition, patients receiving prolonged enteral and parenteral nutrition experience changes in the microbiological composition and diversity of their GI tracts. Research is ongoing to characterize the crosstalk between the microbiome and immune function as targets for drug and nutrition therapy.}, }
@article {pmid32189316, year = {2020}, author = {Konturek, P and Konturek, K and Zopf, Y and Harsch, IA}, title = {[Intestinal microbiota - a vital "organ" with manifold functions].}, journal = {MMW Fortschritte der Medizin}, volume = {162}, number = {Suppl 4}, pages = {9-14}, doi = {10.1007/s15006-020-0228-y}, pmid = {32189316}, issn = {1613-3560}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics ; }, abstract = {BACKGROUND: The intestinal microbiota must be seen as an elementary component of our health.<br><br>METHOD: Review article RESULTS AND CONCLUSIONS: An abnormal gut microbiota (dysbiosis) plays an essential role in the pathogenesis of functional and inflammatory bowel diseases. It is often also associated with diseases outside the intestine. The exact causality remains unclear ("chicken and egg problem"). With the help of prebiotics, probiotics or fecal microbiota therapy, relevant therapeutic effects can be achieved in chronic, dysbiosis-associated diseases. The choice of the preparation depends on the clinical symptoms, the duration of the treatment depends on the particular clinical picture.}, }
@article {pmid32188255, year = {2020}, author = {Rey Rubiano, AM and Reyes, G and Delgado, A}, title = {Management of distal intestinal obstruction syndrome by enteroscopy in a post-lung transplant patient.}, journal = {Revista espanola de enfermedades digestivas}, volume = {112}, number = {4}, pages = {330-331}, doi = {10.17235/reed.2020.6908/2020}, pmid = {32188255}, issn = {1130-0108}, mesh = {Endoscopy, Gastrointestinal ; Humans ; Ileum ; Infant, Newborn ; *Intestinal Obstruction/diagnostic imaging/etiology/surgery ; *Lung Transplantation/adverse effects ; Male ; Meconium ; }, abstract = {This is a case of a male patient who had a post-lung transplant complication given to distal intestinal obstruction by meconium. He was managed with laxative irrigation though enteroscope directly in the ileum with immediate resolution, without complications, avoiding surgical management. No similar cases have been reported.}, }
@article {pmid32185143, year = {2020}, author = {Dorsaz, S and Charretier, Y and Girard, M and Gaïa, N and Leo, S and Schrenzel, J and Harbarth, S and Huttner, B and Lazarevic, V}, title = {Changes in Microbiota Profiles After Prolonged Frozen Storage of Stool Suspensions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {77}, pmid = {32185143}, issn = {2235-2988}, mesh = {Bacteria/*classification/isolation &amp; purification ; Bacteroidetes/*genetics/isolation &amp; purification ; Cryopreservation/methods ; DNA, Bacterial/genetics ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Firmicutes/*genetics/isolation &amp; purification ; Humans ; *Microbiota ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics ; Specimen Handling/methods ; Suspensions ; Time Factors ; }, abstract = {Introduction: Fecal microbiota transplantation (FMT) is recommended as safe and effective treatment for recurrent Clostridioides difficile infections. Freezing the FMT preparation simplifies the process, allowing a single stool sample to be used for multiple receivers and over an extended period of time. We aimed to assess the effect of long-term frozen storage on bacterial taxonomic profiles of a stool suspension prepared for FMT. Methods: DNA was extracted from a stool suspension before freezing and sequentially during the 18-month storage period at -80°C. Two different protocols were used for DNA extraction. The first relied on a classical mechanical and chemical cell disruption to extract both intra- and extracellular DNA; the second included specific pre-treatments aimed at removing free DNA and DNA from human and damaged bacterial cells. Taxonomic profiling of bacterial communities was performed by sequencing of V3-V4 16S rRNA gene amplicons. Results: Microbiota profiles obtained by whole DNA extraction procedure remained relatively stable during frozen storage. When DNA extraction procedure included specific pre-treatments, microbiota similarity between fresh and frozen samples progressively decreased with longer frozen storage times; notably, the abundance of Bacteroidetes decreased in a storage duration-dependent manner. The abundance of Firmicutes, the main butyrate producers in the colon, were not much affected by frozen storage for up to 1 year. Conclusion: Our data show that metataxonomic analysis of frozen stool suspensions subjected to specific pre-treatments prior to DNA extractions might provide an interesting indication of bacterial resistance to stress conditions and thus of chances of survival in FMT recipients.}, }
@article {pmid32185104, year = {2020}, author = {Liu, X and Lv, Q and Ren, H and Gao, L and Zhao, P and Yang, X and Yang, G and Xu, D and Wang, G and Yang, W and Wang, P and Wang, Z and Xing, S}, title = {The altered gut microbiota of high-purine-induced hyperuricemia rats and its correlation with hyperuricemia.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e8664}, pmid = {32185104}, issn = {2167-8359}, abstract = {Some studies on the hyperuricemia (HUA) have focused on intestinal bacteria. To better understand the correlation between gut microbiota and HUA, we established a HUA rat model with high-purine diet, and used 16S rRNA genes sequencing to analyze gut microbiota changes in HUA rats. To analyze the potential role played by gut microbiota in HUA, we altered the gut microbiota of HUA rats with antibiotics, and compared the degree of uric acid elevation between HUA and antibiotic-fed HUA rats (Ab+HUA). Finally, we established a recipient rat model, in which we transplanted fecal microbiota of HUA and normal rats into recipient rats. Three weeks later, we compared the uric acid content of recipient rats. As a result, the diversity and abundance of the gut microbiota had changed in HUA rats. The Ab-fed HUA rats had significantly lower uric acid content compared to the HUA rats, and gut microbiota from HUA rats increased uric acid content of recipient rats. The genera Vallitalea, Christensenella and Insolitispirillum may associate with HUA. Our findings highlight the association between gut microbiota and HUA, and the potential role played by gut microbiota in HUA. We hope that this finding will promote the isolation and culture of HUA-related bacteria and orient HUA-related studies from being correlational to mechanistic. These steps will therefore make it possible for us to treat HUA using gut microbiota as the target.}, }
@article {pmid32183306, year = {2020}, author = {Gryp, T and Huys, GRB and Joossens, M and Van Biesen, W and Glorieux, G and Vaneechoutte, M}, title = {Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients.}, journal = {International journal of molecular sciences}, volume = {21}, number = {6}, pages = {}, pmid = {32183306}, issn = {1422-0067}, support = {G017815N//Fonds Wetenschappelijk Onderzoek/ ; }, mesh = {Amino Acids, Aromatic/metabolism ; Bacteria/classification/isolation &amp; purification/*metabolism ; Cresols/*metabolism ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Humans ; Indican/*metabolism ; Indoleacetic Acids/*metabolism ; Renal Insufficiency, Chronic/*pathology ; Sulfuric Acid Esters/*metabolism ; Toxins, Biological/metabolism ; }, abstract = {In chronic kidney disease (CKD), impaired kidney function results in accumulation of uremic toxins, which exert deleterious biological effects and contribute to inflammation and cardiovascular morbidity and mortality. Protein-bound uremic toxins (PBUTs), such as p-cresyl sulfate, indoxyl sulfate and indole-3-acetic acid, originate from phenolic and indolic compounds, which are end products of gut bacterial metabolization of aromatic amino acids (AAA). This study investigates gut microbial composition at different CKD stages by isolating, identifying and quantifying PBUT precursor-generating bacteria. Fecal DNA extracts from 14 controls and 138 CKD patients were used to quantify total bacterial number and 11 bacterial taxa with qPCR. Moreover, isolated bacteria from CKD 1 and CKD 5 fecal samples were cultured in broth medium supplemented with AAA under aerobic and anaerobic conditions, and classified as PBUT precursor-generators based on their generation capacity of phenolic and indolic compounds, measured with U(H)PLC. In total, 148 different fecal bacterial species were isolated, of which 92 were PBUT precursor-generators. These bacterial species can be a potential target for reducing PBUT plasma levels in CKD. qPCR indicated lower abundance of short chain fatty acid-generating bacteria, Bifidobacterium spp. and Streptococcus spp., and higher Enterobacteriaceae and E. coli with impaired kidney function, confirming an altered gut microbial composition in CKD.}, }
@article {pmid32182248, year = {2020}, author = {Dang, X and Xu, M and Liu, D and Zhou, D and Yang, W}, title = {Assessing the efficacy and safety of fecal microbiota transplantation and probiotic VSL#3 for active ulcerative colitis: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {15}, number = {3}, pages = {e0228846}, pmid = {32182248}, issn = {1932-6203}, mesh = {Administration, Oral ; Colitis, Ulcerative/*therapy ; Combined Modality Therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/drug effects ; Humans ; Probiotics/*administration &amp; dosage/pharmacology ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation is an effective treatment for many gastrointestinal diseases, such as Clostridium difficile infection and inflammatory bowel disease, especially ulcerative colitis. Changes in colonic microflora may play an important role in the pathogenesis of ulcerative colitis, and improvements in the intestinal microflora may relieve the disease. Fecal bacterial transplants and oral probiotics are becoming important ways to relieve active ulcerative colitis.<br><br>PURPOSE: This systematic review with meta-analysis compared the efficacy and safety of basic treatment combined with fecal microbiota transplantation or mixed probiotics therapy in relieving mild to moderate ulcerative colitis.<br><br>METHODS: The PubMed, Embase, and Cochrane libraries (updated September 2019) were searched to identify randomized, placebo-controlled, or head-to-head trials assessing fecal microbiota transplantation or probiotic VSL#3 as induction therapy in active ulcerative colitis. We analyze data using the R program to obtain evidence of direct comparison and to generate intermediate variables for indirect treatment comparisons.<br><br>RESULTS: Seven randomized, double-blind, placebo-controlled trials were used as the sources of the induction data. All treatments were superior to placebo. In terms of clinical remission and clinical response to active ulcerative colitis, direct comparisons showed fecal microbiota transplantation (OR = 3.47, 95% CI = 1.93-6.25) (OR = 2.48, 95% CI = 1.18-5.21) and mixed probiotics VSL#3 (OR = 2.40, 95% CI = 1.49-3.88) (OR = 3.09, 95% CI = 1.53-6.25) to have better effects than the placebo. Indirect comparison showed fecal microbiota transplantation and probiotic VSL#3 did not reach statistical significance either in clinical remission (RR = 1.20, 95% CI = 0.70-2.06) or clinical response (RR = 0.95, 95% CI = 0.62-1.45). In terms of safety, fecal microbiota transplantation (OR = 1.15, 95% CI = 0.51-2.61) and VSL #3 (OR = 0.90, 95% CI = 0.33-2.49) showed no statistically significant increase in adverse events compared with the control group. In terms of serious adverse events, there was no statistical difference between the fecal microbiota transplantation group and the control group (OR = 1.29, 95% CI = 0.46-3.57). The probiotics VSL#3 seems more safer than fecal microbiota transplantation, because serious adverse events were not reported in the VSL#3 articles.<br><br>CONCLUSIONS: Fecal microbiota transplantation or mixed probiotics VSL#3 achieved good results in clinical remission and clinical response in active ulcerative colitis, and there was no increased risk of adverse reactions. There was no statistical difference between the therapeutic effect of fecal microbiota transplantation and that of mixed probiotics VSL#3. However, the use of fecal microbiota transplantation and probiotics still has many unresolved problems in clinical applications, and more randomized controlled trials are required to confirm its efficacy.}, }
@article {pmid32181906, year = {2020}, author = {Leong, KSW and O'Sullivan, JM and Derraik, JGB and Cutfield, WS}, title = {Gut microbiome transfer-Finding the perfect fit.}, journal = {Clinical endocrinology}, volume = {93}, number = {1}, pages = {3-10}, doi = {10.1111/cen.14183}, pmid = {32181906}, issn = {1365-2265}, mesh = {*Clostridium Infections ; *Diabetes Mellitus, Type 2 ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Gut microbiome transfer (GMT; also referred to as faecal microbiota transplantation or FMT) has been propelled from fringe therapy to mainstream science as a highly effective treatment for recurrent Clostridioides difficile infection. As a result, there has been great interest in the potential efficacy and safety of GMT in treating other medical conditions, for example inflammatory bowel disease, and more recently as a novel therapy for obesity and metabolic diseases. For these chronic conditions, the results from clinical trials have been mixed. Further, specifically in obesity and metabolic diseases, there are limited available data, with only a few published studies with a small number of participants and short duration of follow-up. Therefore, this review aims to explore the human, microbial and formulation factors that may affect the success of GMT. This includes various aspects in the preparation and administration of GMT, such as stool processing, modes of delivery, pretreatment with antibiotics and/or bowel lavage, frequency of GMT and possible use of precision bacteriotherapy. In addition, we examine the potential use of GMT in obesity, type 2 diabetes and metabolic diseases based on current available literature, highlighting some recent advances in GMT research in this area, as well as potential adverse effects after GMT therapy.}, }
@article {pmid32179403, year = {2020}, author = {Ávila, PRM and Michels, M and Vuolo, F and Bilésimo, R and Burger, H and Milioli, MVM and Sonai, B and Borges, H and Carneiro, C and Abatti, M and Santana, IVV and Michelon, C and Dal-Pizzol, F}, title = {Protective effects of fecal microbiota transplantation in sepsis are independent of the modulation of the intestinal flora.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {73}, number = {}, pages = {110727}, doi = {10.1016/j.nut.2020.110727}, pmid = {32179403}, issn = {1873-1244}, mesh = {Animals ; Child ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics ; Rats ; *Sepsis/therapy ; }, abstract = {OBJECTIVE: The aim of this study was to investigate the protective effects of probiotics and fecal transplantation on inflammatory and oxidative parameters in the intestines of two rat models of sepsis.<br><br>METHODS: Rats were treated with prebiotics, probiotics, or symbiotics and exposed to lipopolysaccharide (LPS) or zymosan after 15 d to induce endotoxemia. Oxidative damage and inflammation were analyzed, and histologic examination of the intestinal tissue was performed. Fecal microbiota transplantation (FMT) was carried out in LPS- and zymosan-induced rat models of sepsis.<br><br>RESULTS: Supplementation with symbiotics for 15 d effectively reduced the inflammatory parameters compared with supplementation for 7 d. Probiotics, prebiotics, and symbiotics exerted different effects on the evaluated parameters. In general, Lactobacillus rhamnosus and L. casei exerted better local protective effects. Evaluation of the role of the intestinal microbiota through FMT revealed its protective effects irrespective of the previous treatment with probiotics.<br><br>CONCLUSION: Probiotic strains significantly differ among themselves and exert different effects on the host's health. Symbiotics and FMT could offer additional immunomodulatory benefits to drug therapy, thus serving as a new therapeutic alternative in pediatric patients with sepsis.}, }
@article {pmid32176868, year = {2020}, author = {Chen, Y and Zhang, S and Zeng, B and Zhao, J and Yang, M and Zhang, M and Li, Y and Ni, Q and Wu, D and Li, Y}, title = {Transplant of microbiota from long-living people to mice reduces aging-related indices and transfers beneficial bacteria.}, journal = {Aging}, volume = {12}, number = {6}, pages = {4778-4793}, pmid = {32176868}, issn = {1945-4589}, mesh = {Aging/*physiology ; Animals ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Mice, Inbred C57BL ; }, abstract = {A close relationship between age and gut microbiota exists in invertebrates and vertebrates, including humans. Long-living people are a model for studying healthy aging; they also have a distinctive microbiota structure. The relationship between the microbiota of long-living people and aging phenotype remains largely unknown. Herein, the feces of long-living people were transplanted into mice, which were then examined for aging-related indices and beneficial bacteria. Mice transplanted with fecal matter from long-living people (L group) had greater α diversity, more probiotic genera (Lactobacillus and Bifidobacterium), and short-chain fatty acid producing genera (Roseburia, Faecalibacterium, Ruminococcus, Coprococcus) than the control group. L group mice also accumulated less lipofuscin and β-galactosidase and had longer intestinal villi. This study indicates the effects that the gut microbiota from long-living people have on healthy aging.}, }
@article {pmid32173308, year = {2020}, author = {Pérez-Alba, E and Ortíz-Meza, IA and Flores-Gutiérrez, JP and Scharrer, S and Alfaro-Rivera, CG and Camacho-Ortiz, A}, title = {Rapid effect of fecal transplantation on C. difficile colitis.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {44}, number = {6}, pages = {e152-e153}, doi = {10.1016/j.clinre.2020.02.001}, pmid = {32173308}, issn = {2210-741X}, mesh = {Clostridioides difficile ; Duodenal Ulcer/pathology ; Enterocolitis, Pseudomembranous/*therapy ; Fatal Outcome ; Fecal Incontinence/etiology/therapy ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Hemorrhage/etiology ; Humans ; Hypotension/etiology/therapy ; Leukocytosis/etiology/therapy ; Middle Aged ; Shock/etiology ; }, }
@article {pmid32171669, year = {2019}, author = {Majumder, S and Aggarwal, A}, title = {Juvenile idiopathic arthritis and the gut microbiome: Where are we now?.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {33}, number = {6}, pages = {101496}, doi = {10.1016/j.berh.2020.101496}, pmid = {32171669}, issn = {1532-1770}, mesh = {*Arthritis, Juvenile/microbiology ; Enteral Nutrition ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {In recent decades, because of advances in technology there has been an explosion of knowledge on how microbiome affects human health. In most chronic immune-inflammatory diseases, alterations in gut microbiome has been shown. The successful use of faecal microbial transplants for the treatment of clostridium difficile associated diarrhoea has also paved the way for novel therapies. Gut microbiome is affected by early life events like the mode of delivery, breast feeding, the use of antibiotics, etc. and that may have an indirect effect on the developing immune system as well as on the predisposition to juvenile idiopathic arthritis (JIA). Multiple studies have found altered gut microbiome in JIA though no single organism or microbial community has been found to be associated with JIA. In JIA, attempts to modify gut microbiome by using probiotics, exclusive enteral nutrition and other modalities have had variable success. The current review discusses the current data available on gut microbiome in different categories of JIA and how this knowledge can translate into new therapies.}, }
@article {pmid32170542, year = {2020}, author = {Tamez-Torres, KM and Ponce-de-Leon, A and Torres-Gonzalez, P and Perez-Garcia, E and Torres-Veintimilla, E and Valle, MB and Sifuentes-Osornio, J}, title = {High prevalence of MDR gram-negative bacteria in feces of healthy blood donors in Mexico.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {39}, number = {8}, pages = {1439-1444}, pmid = {32170542}, issn = {1435-4373}, support = {289673//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; }, mesh = {Adult ; Anti-Bacterial Agents/*pharmacology ; *Blood Donors ; Carrier State ; Drug Resistance, Multiple, Bacterial ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome ; Gram-Negative Bacteria/drug effects/*isolation &amp; purification ; Humans ; Male ; Mexico/epidemiology ; Middle Aged ; Prevalence ; Prospective Studies ; }, abstract = {During the initial stage of a study to recruit universal intestinal microbiota donors in Mexico City, we found multiple "healthy" subjects that colonized with MDRO (Multidrug-resistant organisms). We aimed to describe clinical and demographic characteristics of these individuals. This was a prospective observational study. Participants were consecutively recruited among blood donors. A fecal sample was collected from each subject and analyzed at the same day in search of MDRO through chromographic culture media and, if growth observed, later confirmed by MALDI-TOF and susceptibility testing in Vitek 2 system. From July 2018 to March 2019, 85 individuals were screened for fecal colonization. Median age was 35 years (IQR 27-46 years), and 48/85 (56.4%) were males. Seventy-two (84.7%) subjects harbored at least one MDRO. ESBL-producing microorganisms were found in 72/85 (84.3%) subjects, and E. coli was the most frequent (63/85, 74.1%). Four samples (2 E. coli, 2 P. aeruginosa, 2.4% each) harbored carbapenem-resistant Enterobacteriaceae (CRE), together with an ESBL-producing microorganism. Antibiotic use (p = 0.06) and PPIs or H2-blockers intake (p = 0.03) were more common in the colonized subjects during the previous 6-month period. We report a high incidence of enteric colonization of healthy subjects with MDRO, a condition that may be related to antibiotics or PPIs/H2-blockers consumption. This surprisingly high MDRO colonization rate in potential FMT donors emphasizes the need for careful screening of donors to avoid possible transmission to FMT recipients.}, }
@article {pmid32170474, year = {2021}, author = {Allegretti, JR and Mehta, SR and Kassam, Z and Kelly, CR and Kao, D and Xu, H and Fischer, M}, title = {Risk Factors that Predict the Failure of Multiple Fecal Microbiota Transplantations for Clostridioides difficile Infection.}, journal = {Digestive diseases and sciences}, volume = {66}, number = {1}, pages = {213-217}, pmid = {32170474}, issn = {1573-2568}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/*diagnosis/*therapy ; Cohort Studies ; Fecal Microbiota Transplantation/*methods/*trends ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Retrospective Studies ; Risk Factors ; Treatment Failure ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI); however, a small percentage of patients fail to achieve cure even after two FMTs. This high-risk cohort remains poorly understood.<br><br>METHODS: We performed a multicenter, multinational retrospective review of patients that underwent at least one FMT for a CDI indication at four academic FMT referrals. Patients' data including CDI, FMT, and FMT variables were assessed. The primary outcome was FMT failure after a second FMT defined as persistent diarrhea and positive laboratory test for C. difficile (PCR or toxin) despite a second FMT within 8&#xa0;weeks of the first FMT. A multivariable logistic regression model was performed to determine predictors of second FMT failure.<br><br>RESULTS: A total of 540 patients received at least one FMT during the study period, of which 432 patients had success following the first FMT, 108 had documented failure (25%). Among those who failed the first FMT, 63 patients received a second FMT, of which 36 achieved cure, and 24 had documented failure after the second FMT. Patients that failed the first FMT but did not receive a second FMT and those lost to follow-up were excluded leaving 492 patients included in the analysis. The second FMT failure rate was 4.8% (24/492). Risk factors for second FMT failure identified by multivariable logistic regression included: inpatient status (OR 7.01, 95% CI: 2.37-20.78), the presence of pseudomembranes (OR 3.53, 95% CI: 1.1-11.33), and immunocompromised state (OR 3.56, 95% CI: 1.45-8.72) at the time of first FMT.<br><br>CONCLUSION: This study identifies clinically relevant risk factors predictive of failing a second FMT. Clinicians can use these variables to help identify high-risk patients and provide a better-informed consent regarding the possibility of needing multiple FMTs.}, }
@article {pmid32169506, year = {2020}, author = {Li, Y and Su, X and Gao, Y and Lv, C and Gao, Z and Liu, Y and Wang, Y and Li, S and Wang, Z}, title = {The potential role of the gut microbiota in modulating renal function in experimental diabetic nephropathy murine models established in same environment.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1866}, number = {6}, pages = {165764}, doi = {10.1016/j.bbadis.2020.165764}, pmid = {32169506}, issn = {1879-260X}, mesh = {Animals ; Bacteria/classification/genetics/pathogenicity ; Blood Glucose/genetics ; Diabetic Nephropathies/chemically induced/*microbiology/pathology ; Disease Models, Animal ; Fatty Acids, Volatile/*metabolism ; Gastrointestinal Microbiome/drug effects/*genetics ; Humans ; Kidney/*metabolism/microbiology/pathology ; Mice ; RNA, Ribosomal, 16S/genetics ; Severity of Illness Index ; Streptozocin/toxicity ; }, abstract = {Recent studies have shown that laboratory murine autoimmunity models under the same environment display different outcomes. We established diabetic nephropathy model mice under the same environment using the classic streptozotocin method. Renal dysfunction was different among the mice. Proteinuria was more significant in the severe proteinuria group (SP) than in the mild proteinuria group (MP). We hypothesized a role for the gut microbiota in the outcome and reproducibility of induced DN models. 16S rDNA gene sequencing technology was used to analyze the differences in the gut microbiota between the two groups. Here, through fecal microbiota transplantation (FMT) and gas chromatography mass spectrometry (GC-MS), we verified the role of the gut microbiota and its short-chain fatty acid (SCFA) generation in DN mouse renal dysfunction. In the SP group, there was a reduced abundance of Firmicutes (P < 0.0001), and the dominant genus Allobaculum [linear discriminant analysis (LDA) >3, P < 0.05] was positively correlated with body weight (Rho = 0.767, P < 0.01) and blood glucose content (Rho = 0.648, P < 0.05), while the dominant genus Anaerosporobacter (LDA > 3, P < 0.05) was positively correlated with 24-hour urinary protein content (Rho = 0.773, P < 0.01). In the MP group, the dominant genus Blautia (LDA > 3, P < 0.05) was negatively correlated with 24-hour urinary protein content (Rho = -0.829, P < 0.05). The results indicated that Allobaculum and Anaerosporobacter may worsen renal function, while Blautia may be a protective factor in DN. These findings suggested that the gut microbiota may contribute to the heterogeneity of the induced response since we observed potential disease-associated microbial taxonomies and correlations with DN.}, }
@article {pmid32168885, year = {2020}, author = {Jo, YJ and Tagele, SB and Pham, HQ and Jung, Y and Ibal, JC and Choi, S and Kang, GU and Park, S and Kang, Y and Kim, S and Koh, H and Shin, JH}, title = {In Situ Profiling of the Three Dominant Phyla Within the Human Gut Using TaqMan PCR for Pre-Hospital Diagnosis of Gut Dysbiosis.}, journal = {International journal of molecular sciences}, volume = {21}, number = {6}, pages = {}, pmid = {32168885}, issn = {1422-0067}, support = {2018M3A9H3025030//National Research Foundation, Korea/ ; 918010-4//Strategic Initiative for Microbiomes in Agriculture and Food, Korea/ ; }, mesh = {Bacteria/*classification/genetics/isolation &amp; purification ; Colitis, Ulcerative/*microbiology ; Dysbiosis/*diagnosis ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Humans ; Multiplex Polymerase Chain Reaction/*methods ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {A microbial imbalance called dysbiosis leads to inflammatory bowel disease (IBD), which can include ulcerative colitis (UC). Fecal microbiota transplantation (FMT), a novel therapy, has recently been successful in treating gut dysbiosis in UC patients. For the FMT technique to be successful, the gut microbiota of both the healthy donors and UC patients must be characterized. For decades, next-generation sequencing (NGS) has been used to analyze gut microbiota. Despite the popularity of NGS, the cost and time constraints make it difficult to use in emergency services and activities related to the periodic monitoring of microbiota profile alterations. Hence, in this study, we developed a multiplex TaqMan qPCR assay (MTq-PCR) with novel probes to simultaneously determine the relative proportions of the three dominant microbial phyla in the human gut: Bacteroidetes, Firmicutes, and Proteobacteria. The relative proportions of the three phyla in fecal samples of either healthy volunteers or UC patients were similar when assessed NGS and the MTq-PCR. Thus, our MTq-PCR assay could be a practical microbiota profiling alternative for diagnosing and monitoring gut dysbiosis in UC patients during emergency situations, and it could have a role in screening stool from potential FMT donors.}, }
@article {pmid32167008, year = {2020}, author = {Yu, L and Wang, L and Yi, H and Wu, X}, title = {Beneficial effects of LRP6-CRISPR on prevention of alcohol-related liver injury surpassed fecal microbiota transplant in a rat model.}, journal = {Gut microbes}, volume = {11}, number = {4}, pages = {1015-1029}, pmid = {32167008}, issn = {1949-0984}, mesh = {Animals ; Bacteria/classification/genetics/*growth &amp; development/isolation &amp; purification ; *CRISPR-Cas Systems ; Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Genetic Therapy ; Liver Cirrhosis, Alcoholic/microbiology/*prevention &amp; control ; Liver Diseases, Alcoholic/microbiology/*therapy ; Low Density Lipoprotein Receptor-Related Protein-6/*genetics/metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Symbiosis ; }, abstract = {Alcohol intake can modify gut microbiota composition, increase gut permeability, and promote liver fibrogenesis. LRP6 is a signal transmembrane protein and a co-receptor for the canonical Wnt signaling pathway. This study compared the curative effect of LRP6-CRISPR on alcohol-related liver injury with that of traditional fecal microbiota transplant (FMT) and investigated the alteration of the gut microbiome following the treatment. A rat model of alcohol-related liver injury was established and injected with lentiviral vectors expressing LRP6-CRISPR or administered with fecal filtrate from healthy rats, with healthy rat served as the control. Liver tissues of rats were examined by HE staining, Sirius staining, and Oil red O staining, respectively. The expression of LRP6 and fibrosis biomarkers were tested by PCR. The fecal sample of rats was collected and examined by 16S rRNA sequencing. Our data indicated that LRP6-CRISPR was more efficient in the prevention of alcohol-related liver injury than FMT. Microbiome analysis showed that alcohol-related liver injury related to gut microbiota dysbiosis, while treatment with LRP6-CRISPR or FMT increased gut microflora diversity and improved gut symbiosis. Further, bacteria specific to the disease stages were identified. Genera Romboutsia, Escherichia-Shigella, Pseudomonas, Turicibacter, and Helicobacter were prevalent in the intestine of rats with alcohol-related liver injury, while the domination of Lactobacillus was found in rats treated with LRP6-CRISPR or FMT. Besides, Lactobacillus and genera belonging to family Lachnospiraceae, Bacteroidales S24-7 group, and Ruminococcaceae were enriched in healthy rats. LRP6-CRISPR and FMT have beneficial effects on the prevention of alcohol-related liver injury, and correspondently, both treatments altered the disrupted gut microflora to a healthy one.}, }
@article {pmid32166622, year = {2021}, author = {Ramai, D and Zakhia, K and Fields, PJ and Ofosu, A and Patel, G and Shahnazarian, V and Lai, JK and Dhaliwal, A and Reddy, M and Chang, S}, title = {Fecal Microbiota Transplantation (FMT) with Colonoscopy Is Superior to Enema and Nasogastric Tube While Comparable to Capsule for the Treatment of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.}, journal = {Digestive diseases and sciences}, volume = {66}, number = {2}, pages = {369-380}, pmid = {32166622}, issn = {1573-2568}, mesh = {Capsules ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/*therapy ; Colonoscopy/*methods/standards ; Enema/*methods/standards ; Fecal Microbiota Transplantation/*methods/standards ; Humans ; Intubation, Gastrointestinal/*methods/standards ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Several routes of fecal microbiota transplantation (FMT) administration are available for treating recurrent Clostridioides difficile infections (CDI), the most recent of which are capsules.<br><br>AIM: To assess the efficacy of colonoscopy, capsule, enema, and nasogastric tube (NGT) FMT for the treatment of recurrent CDI.<br><br>METHODS: We reported clinical outcomes of colonoscopy, capsule, enema, and NGT FMT for the treatment of recurrent CDI according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. During January 2000 to January 2018, three databases were searched: PubMed, EMBASE, and CINAHL. Primary outcome was overall cure rate which was assessed using a random effects model; secondary outcomes included adverse effects as well as subgroup analyses comparing donor relationship, sample preparation, and study design.<br><br>RESULTS: Twenty-six studies (1309 patients) were included in the study. FMT was administered using colonoscopy in 16 studies (483 patients), NGT in five studies (149 patients), enema in four studies (360 patients), and capsules in four studies (301 patients). The random effects of pooled FMT cure rates were colonoscopy 94.8% (CI 92.4-96.8%; I[2] 15.6%), capsule 92.1% (CI 88.6-95.0%; I[2] 7.1%), enema 87.2% (CI 83.4-90.5%; I[2] 0%), and NGT/NDT 78.1% (CI 71.6-84.1%; I[2] 0%). On subgroup analysis of colonoscopy FMT, sample preparation methods had comparable cure rates: fresh 94.9% compared to 94.5%. Similarly, cure rates were unaffected by donor relationship: mixed 94.5% compared to unrelated donor 95.7%.<br><br>CONCLUSION: CDI cure rates with FMT performed with colonoscopy are superior to enema and NGT FMT, while those with FMT with colonoscopy and capsule are comparable.}, }
@article {pmid32165408, year = {2020}, author = {Rasmussen, TS and Mentzel, CMJ and Kot, W and Castro-Mejía, JL and Zuffa, S and Swann, JR and Hansen, LH and Vogensen, FK and Hansen, AK and Nielsen, DS}, title = {Faecal virome transplantation decreases symptoms of type 2 diabetes and obesity in a murine model.}, journal = {Gut}, volume = {69}, number = {12}, pages = {2122-2130}, doi = {10.1136/gutjnl-2019-320005}, pmid = {32165408}, issn = {1468-3288}, mesh = {Animals ; Blood Glucose/analysis ; Diabetes Mellitus, Experimental/therapy ; Diabetes Mellitus, Type 2/*therapy ; Diet, High-Fat ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Gene Expression ; Insulin-Like Growth Factor Binding Protein 2/genetics/metabolism ; Klotho Proteins ; Membrane Proteins/genetics/metabolism ; Metabolome ; Mice, Inbred C57BL ; Obesity/*therapy ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism ; Proof of Concept Study ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; Receptors, G-Protein-Coupled/genetics/metabolism ; Receptors, Leptin/genetics/metabolism ; Suppressor of Cytokine Signaling 3 Protein/genetics/metabolism ; *Virome ; Weight Gain ; }, abstract = {OBJECTIVE: Development of obesity and type 2 diabetes (T2D) are associated with gut microbiota (GM) changes. The gut viral community is predominated by bacteriophages (phages), which are viruses that attack bacteria in a host-specific manner. The antagonistic behaviour of phages has the potential to alter the GM. As a proof-of-concept, we demonstrate the efficacy of faecal virome transplantation (FVT) from lean donors for shifting the phenotype of obese mice into closer resemblance of lean mice.<br><br>DESIGN: The FVT consisted of viromes with distinct profiles extracted from the caecal content of mice from different vendors that were fed a low-fat (LF) diet for 14 weeks. Male C57BL/6NTac mice were divided into five groups: LF (as diet control), high-fat (HF) diet, HF+ampicillin (Amp), HF+Amp+FVT and HF+FVT. At weeks 6 and 7 of the study, the HF+FVT&#x2009;and HF+Amp+FVT mice were treated with FVT by oral gavage. The Amp groups were treated with Amp 24&#x2009;hours prior to first FVT treatment.<br><br>RESULTS: Six weeks after first FVT, the HF+FVT mice showed a significant decrease in weight gain compared with the HF group. Further, glucose tolerance was comparable between the LF and HF+FVT mice, while the other HF groups all had impaired glucose tolerance. These observations were supported by significant shifts in GM composition, blood plasma metabolome and expression levels of genes associated with obesity and T2D development.<br><br>CONCLUSIONS: Transfer of caecal viral communities from mice with a lean phenotype into mice with an obese phenotype led to reduced weight gain and normalised blood glucose parameters relative to lean mice. We hypothesise that this effect is mediated via FVT-induced GM changes.}, }
@article {pmid32161034, year = {2020}, author = {}, title = {No benefit of faecal microbiota transplantation for IBS-D.}, journal = {Drug and therapeutics bulletin}, volume = {58}, number = {6}, pages = {87}, doi = {10.1136/dtb.2020.000013}, pmid = {32161034}, issn = {1755-5248}, abstract = {Review of: Aroniadis OC, Brandt LJ, Oneto C, et al Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial. Lancet Gastroenterol Hepatol 2019;4:675-85.}, }
@article {pmid32158569, year = {2020}, author = {AlQahtani, H and Baloch, S and Tabb, D}, title = {Treatment of Recurrent Clostridium difficile Infection in an Immunocompromised Patient with Severe Neutropenia Not Responding to Standard Therapy.}, journal = {Case reports in infectious diseases}, volume = {2020}, number = {}, pages = {3089023}, pmid = {32158569}, issn = {2090-6625}, abstract = {One of the most effective strategies in reducing the risk of Clostridium difficile infection (CDI) recurrence is fecal microbiota transplantation (FMT). However, several adverse events have been reported post FMT, and data on the efficacy and safety of FMT in immunocompromised patients with hematological malignancies are rare. This report presents FMT treatment for refractory CDI in a severely immunocompromised patient. A 69-year-old female presented to the emergency department complaining of foul smelling, intractable, watery diarrhea and generalized abdominal pain. She was recently diagnosed with high-risk myelodysplastic Syndrome (MDS) requiring daily blood transfusions and reported multiple CDI episodes in the past treated successfully with metronidazole and vancomycin as mono- or combotherapy. During this admission, treatment with oral vancomycin (high dose) and intravenous metronidazole was unsuccessful, so FMT was administered. The patient recovered well despite an absolute neutrophil count (ANC) < 0.25 × 10[9]/L, and chemotherapy was initiated soon after. FMT was successful and safe in this patient, with no relapse and adverse events seen in 8 weeks of follow-up via phone calls and office visits.}, }
@article {pmid32157661, year = {2020}, author = {Zhu, T and Goodarzi, MO}, title = {Metabolites Linking the Gut Microbiome with Risk for Type 2 Diabetes.}, journal = {Current nutrition reports}, volume = {9}, number = {2}, pages = {83-93}, pmid = {32157661}, issn = {2161-3311}, support = {R01 DK109588/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acids, Branched-Chain/metabolism ; Animals ; Bile Acids and Salts/metabolism ; Diabetes Mellitus, Type 2/*microbiology/therapy ; Diet Therapy ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Host Microbial Interactions ; Humans ; Imidazoles/metabolism ; Indoles/metabolism ; Insulin Resistance/physiology ; Methylamines/metabolism ; Mice ; Probiotics/therapeutic use ; Rats ; }, abstract = {PURPOSE OF REVIEW: An increasing body of evidence suggests that the gut microbiome influences the pathogenesis of insulin resistance and type 2 diabetes (T2D). In this review, we will discuss the latest findings regarding the mechanisms linking the gut microbiome and microbial metabolites with T2D and therapeutic approaches based on the gut microbiota for the prevention and treatment of T2D.<br><br>RECENT FINDINGS: Alterations in the gut microbial composition are associated with the risk of T2D. The gut microbiota can metabolize dietary- and host-derived factors to produce numerous microbial metabolites, which are involved in metabolic processes modulating nutrition and energy harvest, gut barrier function, systemic inflammation, and glucose metabolism. Microbial metabolites are important mediators of microbial-host crosstalk impacting host glucose metabolism. Furthermore, microbiome-based interventions may have beneficial effects on glycemic control. Future research is required to develop personalized T2D therapy based on microbial composition and/or metabolites.}, }
@article {pmid32156514, year = {2020}, author = {Ren, K}, title = {Commentary on Ma et al. Resveratrol brings back happy bug's harmony.}, journal = {Brain, behavior, and immunity}, volume = {87}, number = {}, pages = {197-198}, doi = {10.1016/j.bbi.2020.03.005}, pmid = {32156514}, issn = {1090-2139}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Pain ; Resveratrol ; Temporomandibular Joint ; }, }
@article {pmid32156316, year = {2020}, author = {Huang, Z and Zeng, S and Xiong, J and Hou, D and Zhou, R and Xing, C and Wei, D and Deng, X and Yu, L and Wang, H and Deng, Z and Weng, S and Kriengkrai, S and Ning, D and Zhou, J and He, J}, title = {Microecological Koch's postulates reveal that intestinal microbiota dysbiosis contributes to shrimp white feces syndrome.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {32}, pmid = {32156316}, issn = {2049-2618}, mesh = {Animals ; Bacteria/classification/isolation &amp; purification ; Dysbiosis/*microbiology ; Fecal Microbiota Transplantation/*veterinary ; Feces/microbiology ; *Gastrointestinal Microbiome ; Genetic Variation ; Intestines/*microbiology/physiopathology ; Penaeidae/*microbiology ; }, abstract = {BACKGROUND: Recently, increasing evidence supports that some complex diseases are not attributed to a given pathogen, but dysbiosis in the host intestinal microbiota (IM). The full intestinal ecosystem alterations, rather than a single pathogen, are associated with white feces syndrome (WFS), a globally severe non-infectious shrimp disease, while no experimental evidence to explore the causality. Herein, we conducted comprehensive metagenomic and metabolomic analysis, and intestinal microbiota transplantation (IMT) to investigate the causal relationship between IM dysbiosis and WFS.<br><br>RESULTS: Compared to the Control shrimp, we found dramatically decreased microbial richness and diversity in WFS shrimp. Ten genera, such as Vibrio, Candidatus Bacilloplasma, Photobacterium, and Aeromonas, were overrepresented in WFS, whereas 11 genera, including Shewanella, Chitinibacter, and Rhodobacter were enriched in control. The divergent changes in these populations might contribute the observation that a decline of pathways conferring lipoic acid metabolism and mineral absorption in WFS. Meanwhile, some sorts of metabolites, especially lipids and organic acids, were found to be related to the IM alteration in WFS. Integrated with multiomics and IMT, we demonstrated that significant alterations in the community composition, functional potentials, and metabolites of IM were closely linked to shrimp WFS. The distinguished metabolites which were attributed to the IM dysbiosis were validated by feed-supplementary challenge. Both homogenous selection and heterogeneous selection process were less pronounced in WFS microbial community assembly. Notably, IMT shrimp from WFS donors eventually developed WFS clinical signs, while the dysbiotic IM can be recharacterized in recipient shrimp.<br><br>CONCLUSIONS: Collectively, our findings offer solid evidence of the causality between IM dysbiosis and shrimp WFS, which exemplify the 'microecological Koch's postulates' (an intestinal microbiota dysbiosis, a disease) in disease etiology, and inspire our cogitation on etiology from an ecological perspective. Video abstract.}, }
@article {pmid32155452, year = {2020}, author = {Mendizabal, M and Haddad, L and Marciano, S and Ganem, FO and Paz, S and Gruz, F and Ridruejo, E and Lurbet, MF and Fernandez, N and Descalzi, V and Anders, M and Gadano, A and Martínez, A and Silva, YM}, title = {Hepatitis E infection is an infrequent cause of acute hepatitis in the metropolitan area of Buenos Aires.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {126}, number = {}, pages = {104309}, doi = {10.1016/j.jcv.2020.104309}, pmid = {32155452}, issn = {1873-5967}, mesh = {Acute Disease/epidemiology ; Adult ; Argentina/epidemiology ; Cities/epidemiology ; Female ; Genotype ; Hepatitis Antibodies/*blood ; Hepatitis E/*epidemiology ; Hepatitis E virus/genetics ; Hepatitis, Viral, Human/*epidemiology ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Liver Failure, Acute/epidemiology/*virology ; Male ; Middle Aged ; Prospective Studies ; RNA, Viral/blood ; Seroepidemiologic Studies ; }, abstract = {UNLABELLED: Background Argentina is considered a region of low seroprevalence of hepatitis E virus (HEV), however; no studies have evaluated its burden among acute hepatitis cases.<br><br>OBJECTIVES: We aimed to estimate the proportion of acute HEV and outcome in a cohort of patients with acute hepatitis from 6 liver units in the Metropolitan area of Buenos Aires (MABA).<br><br>STUDY DESIGN: We performed a prospective cohort study including patients &#x2265;18 years with acute hepatitis (increase in transaminases x 5 ULN) fromJuly 2016 to May 2018. Severe hepatitis was defined as acute hepatitis + INR> 1.5 and acute liver failure as severe hepatitis + encephalopathy. In patients in whom other etiologies were excluded, HEV tests were performed: anti-HEV IgM/G and HEV-RNA in serum and feces.<br><br>RESULTS: Overall, 268 patients with acute hepatitis were included in the study. The most frequent etiologies of acute hepatitis were hepatitis B (67patients, 25 %), hepatotoxicity (65, 24 %) and autoimmune hepatitis (26, 10 %). Acute HEV infection was confirmed in 8 (2.98 %; 95 %CI 1.25-5.63) patients who tested positive for anti-HEV IgM. A total of 63 (23.5 %) patients were hospitalized and 9 (3.3 %) patients died. Overall, 48 (18 %) patients developed severe hepatitis, 6 (2.2 %) have acute liver failure, 6 (1.9 %) underwent liver transplantation and 9 (3.4 %) patients died.<br><br>CONCLUSIONS: the proportion of acute HEV in MABA was low during the period studied. We believe our findings will aid physicians prioritize other etiologies of acute hepatitis over HEV in order to optimize diagnostic resources and offer better care to their patients.}, }
@article {pmid32155205, year = {2020}, author = {McKinney, CA and Oliveira, BCM and Bedenice, D and Paradis, MR and Mazan, M and Sage, S and Sanchez, A and Widmer, G}, title = {The fecal microbiota of healthy donor horses and geriatric recipients undergoing fecal microbial transplantation for the treatment of diarrhea.}, journal = {PloS one}, volume = {15}, number = {3}, pages = {e0230148}, pmid = {32155205}, issn = {1932-6203}, support = {R21 AI125891/AI/NIAID NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Colitis/therapy/veterinary ; Diarrhea/*therapy/veterinary ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/genetics ; High-Throughput Nucleotide Sequencing/methods ; Horses/microbiology ; Microbiota ; RNA, Ribosomal, 16S/genetics ; Tissue Donors ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Fecal microbial transplantation (FMT), a treatment for certain gastrointestinal conditions associated with dysbiosis in people, is also empirically employed in horses with colitis. This study used microbiota high-throughput sequencing to compare the fecal microbial profile of healthy horses to that of geriatric microbial transplant recipients experiencing diarrhea and tested whether FMT restores microbiota diversity.<br><br>METHODS: To evaluate the effect of environment and donor characteristics on the intestinal microbiota, fecal samples were collected per rectum from 15 healthy young-adult (2-12 years) and 15 geriatric (&#x2265;20 years) horses. Additionally, FMT was performed for 3 consecutive days in 5 geriatric horses with diarrhea using feces from the same healthy donor. Fecal samples were collected from both donor and recipient prior to each FMT and from recipients 24 hours following the last FMT. The profile of the fecal bacterial microbiota was compared using 16S amplicon sequencing.<br><br>RESULTS AND CONCLUSIONS: In contrast to diet and farm location, age did not significantly affect the healthy equine fecal microbiota, indicating that both healthy geriatric and young-adult horses may serve as FMT donors. The fecal microbiota of horses with diarrhea was significantly more variable in terms of &#x3b2;-diversity than that of healthy horses. An inverse correlation between diarrhea score and relative abundance of Verrucomicrobia was identified in surviving FMT recipients. At study completion, the fecal microbiota of horses which responded to FMT had a higher &#x3b1;-diversity than prior to treatment and was phylogenetically more similar to that of the donor.}, }
@article {pmid32154322, year = {2020}, author = {Keen, EC and Tasoff, P and Hink, T and Reske, KA and Burnham, CD and Dantas, G and Kwon, JH and Dubberke, ER}, title = {Microbiome Restoration by RBX2660 Does Not Preclude Recurrence of Multidrug-Resistant Urinary Tract Infection Following Subsequent Antibiotic Exposure: A Case Report.}, journal = {Open forum infectious diseases}, volume = {7}, number = {3}, pages = {ofaa042}, pmid = {32154322}, issn = {2328-8957}, support = {K23 AI137321/AI/NIAID NIH HHS/United States ; R01 HD092414/HD/NICHD NIH HHS/United States ; U01 AI123394/AI/NIAID NIH HHS/United States ; }, abstract = {A 62-year-old woman received RBX2660, an investigational microbiome restoration therapeutic, for recurrent multidrug-resistant (MDR) urinary tract infection (UTI). RBX2660 increased gut microbiome diversity but did not eliminate uropathogen carriage, and MDR UTI recurred after subsequent antibiotic exposure. Thus, restoration of microbiome diversity does not preclude disease recurrence by residual MDR pathogens.}, }
@article {pmid32150549, year = {2020}, author = {Yu, EW and Gao, L and Stastka, P and Cheney, MC and Mahabamunuge, J and Torres Soto, M and Ford, CB and Bryant, JA and Henn, MR and Hohmann, EL}, title = {Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial.}, journal = {PLoS medicine}, volume = {17}, number = {3}, pages = {e1003051}, pmid = {32150549}, issn = {1549-1676}, support = {P30 DK020579/DK/NIDDK NIH HHS/United States ; P30 DK040561/DK/NIDDK NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Biomarkers/blood ; Boston ; Double-Blind Method ; *Energy Metabolism ; *Fecal Microbiota Transplantation/adverse effects ; Female ; *Gastrointestinal Microbiome ; Humans ; *Insulin Resistance ; Intestines/*microbiology ; Male ; Middle Aged ; Obesity/diagnosis/metabolism/microbiology/*therapy ; Pilot Projects ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity.<br><br>METHODS AND FINDINGS: FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 &#xb1; 6.7 kg/m2 and 41.3 &#xb1; 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% &#xb1; 12% in FMT group versus -3% &#xb1; 32% in placebo group, mean difference 9%, 95% CI -5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI -0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference -0.1 kg, 95% CI -1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI -0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention.<br><br>CONCLUSIONS: Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT02530385.}, }
@article {pmid32148376, year = {2020}, author = {Gupta, A and Saha, S and Khanna, S}, title = {Therapies to modulate gut microbiota: Past, present and future.}, journal = {World journal of gastroenterology}, volume = {26}, number = {8}, pages = {777-788}, pmid = {32148376}, issn = {2219-2840}, mesh = {Fecal Microbiota Transplantation/*trends ; Feces/*microbiology ; *Forecasting ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {The human gut microbiota comprises of a complex and diverse array of microorganisms, and over the years the interaction between human diseases and the gut microbiota has become a subject of growing interest. Disturbed microbial milieu in the gastrointestinal tract is central to the pathogenesis of several diseases including antibiotic-associated diarrhea and Clostridioides difficile infection (CDI). Manipulation of this microbial milieu to restore balance by microbial replacement therapies has proven to be a safe and effective treatment for recurrent CDI. There is considerable heterogeneity in various aspects of stool processing and administration for fecal microbiota transplantation (FMT) across different centers globally, and standardized microbioal replacement therapies offer an attractive alternative. The adverse effects associated with FMT are usually mild. However, there is paucity of data on long term safety of FMT and there is a need for further studies in this regard. With our increasing understanding of the host-microbiome interaction, there is immense potential for microbial replacement therapies to emerge as a treatment option for several diseases. The role of microbioal replacement therapies in diseases other than CDI is being extensively studied in ongoing clinical trials and it may be a potential treatment option for inflammatory bowel disease, irritable bowel syndrome, obesity, multidrug resistant infections, and neuropsychiatric illnesses. Fecal microbiota transplantation for non-CDI disease states should currently be limited only to research settings.}, }
@article {pmid32146836, year = {2020}, author = {Giuffrè, M and Campigotto, M and Campisciano, G and Comar, M and Crocè, LS}, title = {A story of liver and gut microbes: how does the intestinal flora affect liver disease? A review of the literature.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {318}, number = {5}, pages = {G889-G906}, doi = {10.1152/ajpgi.00161.2019}, pmid = {32146836}, issn = {1522-1547}, mesh = {Animals ; Bacteria/metabolism/*pathogenicity ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology ; Liver/metabolism/*microbiology/pathology ; Liver Diseases/metabolism/*microbiology/pathology/therapy ; Probiotics/therapeutic use ; }, abstract = {Each individual is endowed with a unique gut microbiota (GM) footprint that mediates numerous host-related physiological functions, such as nutrient metabolism, maintenance of the structural integrity of the gut mucosal barrier, immunomodulation, and protection against microbial pathogens. Because of increased scientific interest in the GM, its central role in the pathophysiology of many intestinal and extraintestinal conditions has been recognized. Given the close relationship between the gastrointestinal tract and the liver, many pathological processes have been investigated in the light of a microbial-centered hypothesis of hepatic damage. In this review we introduce to neophytes the vast world of gut microbes, including prevalent bacterial distribution in healthy individuals, how the microbiota is commonly analyzed, and the current knowledge of the role of GM in liver disease pathophysiology. Also, we highlight the potentials and downsides of GM-based therapy.}, }
@article {pmid32142785, year = {2020}, author = {Gu, J and Han, B and Wang, J}, title = {COVID-19: Gastrointestinal Manifestations and Potential Fecal-Oral Transmission.}, journal = {Gastroenterology}, volume = {158}, number = {6}, pages = {1518-1519}, pmid = {32142785}, issn = {1528-0012}, mesh = {Betacoronavirus/classification/genetics/*isolation &amp; purification ; COVID-19 ; Coronavirus Infections/*complications/pathology/*transmission ; Feces/virology ; Gastrointestinal Diseases/*etiology/pathology/*virology ; Humans ; Pandemics ; Pneumonia, Viral/*complications/pathology/*transmission ; SARS-CoV-2 ; }, }
@article {pmid32134837, year = {2020}, author = {Roth, EM and Lee, EJ and Cameron, AM and Shen, NT and Brown, RS and DiMartini, AF and Shenoy, A}, title = {A Young Patient with Brief Alcohol Use and Rapidly Progressive Alcohol-Related Hepatitis: Considerations in Transplant Eligibility.}, journal = {Harvard review of psychiatry}, volume = {28}, number = {2}, pages = {133-142}, doi = {10.1097/HRP.0000000000000249}, pmid = {32134837}, issn = {1465-7309}, mesh = {Adult ; Alcohol Drinking/*adverse effects ; Diagnosis, Differential ; End Stage Liver Disease/*etiology ; Fatal Outcome ; Hepatitis, Alcoholic/*diagnosis/therapy ; Humans ; Liver Transplantation ; Male ; Melena/etiology ; Mental Disorders/*complications ; }, }
@article {pmid32133112, year = {2020}, author = {Veryan, J and Forrest, EH}, title = {Recent advances in alcoholic hepatitis.}, journal = {Frontline gastroenterology}, volume = {11}, number = {2}, pages = {133-139}, pmid = {32133112}, issn = {2041-4137}, abstract = {Alcoholic hepatitis (AH) is an acute deterioration in liver function seen in the context of prolonged excessive alcohol consumption and is characterised by the rapid onset of jaundice. The diagnosis of AH has been controversial for many years: it is now accepted that there are clear clinical criteria which can be used to diagnose AH without the need for a liver biopsy. Corticosteroids remain the only treatment proven to be effective in reducing short-term mortality in severe AH; abstinence from alcohol is the most important factor in determining long-term survival. It is recommended a trial of corticosteroid therapy is considered only in those patients with high baseline 'static' scores (Glasgow Alcoholic Hepatitis score and model for end-stage liver disease). Response to corticosteroid therapy should be assessed using a 'dynamic' score such as the Lille score at day 7, with corticosteroids continuing only in patients with a favourable score. Infection and acute kidney injury are associated with poorer outcomes in AH. Early screening for and treatment of infection is recommended with antibiotic therapy overlapping with any subsequent corticosteroid treatment. A biomarker which predicts benefit from corticosteroids at baseline would avoid a trial of therapy to determine response. More efficacious therapeutic options for AH patients are required with N-acetylcysteine, granulocyte colony stimulating factor, faecal microbiota transplantation and routine antibiotics showing promise, but adequate controlled trials are needed to confirm efficacy. Liver transplant has an emerging role for some patients with severe AH not responding to corticosteroids and is likely to become more acceptable with improved methods of patient selection.}, }
@article {pmid32133003, year = {2020}, author = {Rogala, AR and Oka, A and Sartor, RB}, title = {Strategies to Dissect Host-Microbial Immune Interactions That Determine Mucosal Homeostasis vs. Intestinal Inflammation in Gnotobiotic Mice.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {214}, pmid = {32133003}, issn = {1664-3224}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; }, mesh = {Animals ; Bacteria/immunology ; Disease Models, Animal ; Fecal Microbiota Transplantation/methods ; Gastroenteritis/*immunology/microbiology ; Gastrointestinal Microbiome/immunology ; *Germ-Free Life ; Homeostasis/*immunology ; Host Microbial Interactions/*immunology ; Humans ; Inflammatory Bowel Diseases/immunology/microbiology ; Intestinal Mucosa/*immunology ; Mice ; }, abstract = {When identifying the key immunologic-microbial interactions leading to either mucosal homeostasis in normal hosts or intestinal inflammatory responses in genetically susceptible individuals, it is important to not only identify microbial community correlations but to also define the functional pathways involved. Gnotobiotic rodents are a very effective tool for this purpose as they provide a highly controlled environment in which to identify the function of complex intestinal microbiota, their individual components, and metabolic products. Herein we review specific strategies using gnotobiotic mice to functionally evaluate the role of various intestinal microbiota in host responses. These studies include basic comparisons between host responses in germ-free (GF), specific-pathogen-free or conventionally raised wild-type mice or those with underlying genetic susceptibilities to intestinal inflammation. We also discuss what can be learned from studies in which GF mice are colonized with single wild-type or genetically-modified microbial isolates to examine the functions of individual bacteria and their targeted bacterial genes, or colonized by multiple defined isolates to determine interactions between members of defined consortia. Additionally, we discuss studies to identify functions of complex microbial communities from healthy or diseased human or murine hosts via fecal transplant into GF mice. Finally, we conclude by suggesting ways to improve studies of immune-microbial interactions using gnotobiotic mice.}, }
@article {pmid32132347, year = {2020}, author = {Zhang, F and Zhai, M and Wu, Q and Jia, X and Wang, Y and Wang, N}, title = {Protective Effect of Tong-Qiao-Huo-Xue Decoction on Inflammatory Injury Caused by Intestinal Microbial Disorders in Stroke Rats.}, journal = {Biological &amp; pharmaceutical bulletin}, volume = {43}, number = {5}, pages = {788-800}, doi = {10.1248/bpb.b19-00847}, pmid = {32132347}, issn = {1347-5215}, mesh = {Animals ; Anti-Inflammatory Agents/pharmacology/*therapeutic use ; Brain/drug effects/immunology/pathology ; Brain Ischemia/*drug therapy/immunology/microbiology/pathology ; Drugs, Chinese Herbal/pharmacology/*therapeutic use ; Dysbiosis/*drug therapy/immunology/microbiology/pathology ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Intestine, Small/drug effects/immunology/microbiology ; Intraepithelial Lymphocytes/drug effects/immunology ; Ischemic Stroke/*drug therapy/immunology/microbiology/pathology ; Male ; Neuroprotective Agents/pharmacology/*therapeutic use ; Rats, Sprague-Dawley ; T-Lymphocytes, Regulatory/drug effects/immunology ; }, abstract = {Tong-Qiao-Huo-Xue Decoction (TQHXD) is a classic traditional Chinese medicine prescription for treating cerebral ischemia. The purpose of this study was to investigate the effect of TQHXD on intervening inflammatory response of ischemic stroke by regulating intestinal flora and repairing the intestinal barrier. A rat model of cerebral ischemia was established using middle cerebral artery occlusion (MCAO) and behavioral scores were performed. Additionally, the high throughput 16S ribosomal DNA (rDNA) sequence of intestinal bacteria in fecal samples of rat was also carried out. Our results showed that TQHXD could change the main components of intestinal flora in stroke rats, and reduced the excessive increase of Bacteroidetes, and also regulated the abnormal changes of abundance of some flora as well. In addition, the intestinal epithelial barrier was damaged after stroke, allowing bacterial metabolites to enter the blood, while TQHXD had an improved effect on this phenomenon. Meanwhile, pathological changes in the brain tissue and infarct volume were also alleviated by TQHXD. Due to the disorder of the intestinal flora and the destruction of the barrier, the peripheral immune imbalance caused an inflammatory reaction. TQHXD improved the imbalance of T cells, and inhibited the inflammatory response. Finally, the therapeutic transplantation of fecal microbiota also improved the outcome of stroke in rats. Our presented results suggest that TQHXD may improve the gut microbiota disorder and its induced inflammatory response after stroke, which could be a new target and mechanism for the treatment of stroke.}, }
@article {pmid32130695, year = {2020}, author = {Baffy, G}, title = {Gut Microbiota and Cancer of the Host: Colliding Interests.}, journal = {Advances in experimental medicine and biology}, volume = {1219}, number = {}, pages = {93-107}, pmid = {32130695}, issn = {0065-2598}, mesh = {Dysbiosis ; Gastrointestinal Microbiome/immunology/*physiology ; Humans ; Intestines/immunology/microbiology ; Neoplasms/immunology/*metabolism/therapy ; Tumor Microenvironment ; }, abstract = {Cancer develops in multicellular organisms from cells that ignore the rules of cooperation and escape the mechanisms of anti-cancer surveillance. Tumorigenesis is jointly encountered by the host and microbiota, a vast collection of microorganisms that live on the external and internal epithelial surfaces of the body. The largest community of human microbiota resides in the gastrointestinal tract where commensal, symbiotic and pathogenic microorganisms interact with the intestinal barrier and gut mucosal lymphoid tissue, creating a tumor microenvironment in which cancer cells thrive or perish. Aberrant composition and function of the gut microbiota (dysbiosis) has been associated with tumorigenesis by inducing inflammation, promoting cell growth and proliferation, weakening immunosurveillance, and altering food and drug metabolism or other biochemical functions of the host. However, recent research has also identified several mechanisms through which gut microbiota support the host in the fight against cancer. These mechanisms include the use of antigenic mimicry, biotransformation of chemotherapeutic agents, and other mechanisms to boost anti-cancer immune responses and improve the efficacy of cancer immunotherapy. Further research in this rapidly advancing field is expected to identify additional microbial metabolites with tumor suppressing properties, map the complex interactions of host-microbe 'transkingdom network' with cancer cells, and elucidate cellular and molecular pathways underlying the impact of specific intestinal microbial configurations on immune checkpoint inhibitor therapy.}, }
@article {pmid32129694, year = {2020}, author = {Rodríguez, C and Romero, E and Garrido-Sanchez, L and Alcaín-Martínez, G and Andrade, RJ and Taminiau, B and Daube, G and García-Fuentes, E}, title = {MICROBIOTA INSIGHTS IN CLOSTRIDIUM DIFFICILE INFECTION AND INFLAMMATORY BOWEL DISEASE.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1725220}, pmid = {32129694}, issn = {1949-0984}, mesh = {Clostridioides difficile/isolation &amp; purification ; Dysbiosis/*microbiology ; Enterocolitis, Pseudomembranous/*microbiology/pathology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Intestines/microbiology/pathology ; }, abstract = {Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation that includes Crohn´s disease (CD) and ulcerative colitis (UC). Although the etiology is still unknown, some specific factors have been directly related to IBD, including genetic factors, abnormal intestinal immunity, and/or gut microbiota modifications. Recent findings highlight the primary role of the gut microbiota closely associated with a persistent inappropriate inflammatory response. This gut environment of dysbiosis in a susceptible IBD host can increasingly worsen and lead to colonization and infection with some opportunistic pathogens, especially Clostridium difficile. C. difficile is an intestinal pathogen considered the main cause of antibiotic-associated diarrhea and colitis and an important complication of IBD, which can trigger or worsen an IBD flare. Recent findings have highlighted the loss of bacterial cooperation in the gut ecosystem, as well as the pronounced intestinal dysbiosis, in patients suffering from IBD and concomitant C. difficile infection (CDI). The results of intestinal microbiota studies are still limited and often difficult to compare because of the variety of disease conditions. However, these data provide important clues regarding the main modifications and interrelations in the complicated gut ecosystem to better understand both diseases and to take advantage of the development of new therapeutic strategies. In this review, we analyze in depth the gut microbiota changes associated with both forms of IBD and CDI and their similarity with the dysbiosis that occurs in CDI. We also discuss the metabolic pathways that favor the proliferation or decrease in several important taxa directly related to the disease.}, }
@article {pmid32126303, year = {2020}, author = {Ebrahimzadeh Leylabadlo, H and Sanaie, S and Sadeghpour Heravi, F and Ahmadian, Z and Ghotaslou, R}, title = {From role of gut microbiota to microbial-based therapies in type 2-diabetes.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {81}, number = {}, pages = {104268}, doi = {10.1016/j.meegid.2020.104268}, pmid = {32126303}, issn = {1567-7257}, mesh = {Animals ; Diabetes Mellitus, Type 2/*microbiology/*therapy ; Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Prebiotics/microbiology ; Probiotics/therapeutic use ; }, abstract = {The incidence of type 2 diabetes mellitus (T2DM) has increased dramatically at an alarming level around the world.T2DM is associated with changeable risk factors in lifestyle as well as genetic and family associated risk factors. More importantly, imbalanced or impaired gut microbial distribution (dysbiosis) has been reported as a contributing risk factor in insulin resistance progression in T2DM. Dysbiosis may restructure the metabolic and functional pathways in the intestine which are involved in the development of T2DM. However, several studies have indicated the constructive and helpful effect of prebiotics, probiotics, and fecal microbiota transplantation (FMT) on the improvement of gut microbiota (GM) and accordingly host metabolism. In this review, the association between GM and T2DM have been evaluated and the role of prebiotics, probiotics and FMT, as potential therapeutic approaches have been discussed. Relevant studies were obtained randomly from online databases such as PubMed/Medline and ISI Web of Science.}, }
@article {pmid32117913, year = {2020}, author = {Adamberg, K and Raba, G and Adamberg, S}, title = {Use of Changestat for Growth Rate Studies of Gut Microbiota.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {8}, number = {}, pages = {24}, pmid = {32117913}, issn = {2296-4185}, abstract = {Human colon microbiota, composed of hundreds of different species, is closely associated with several health conditions. Controlled in vitro cultivation and up-to-date analytical methods make possible the systematic evaluation of the underlying mechanisms of complex interactions between the members of microbial consortia. Information on reproducing fecal microbial consortia can be used for various clinical and biotechnological applications. In this study, chemostat and changestat cultures were used to elucidate the effects of the physiologically relevant range of dilution rates on the growth and metabolism of adult fecal microbiota. The dilution rate was kept either at D = 0.05 or D = 0.2 1/h in chemostat cultures, while gradually changing from 0.05 to 0.2 1/h in the A-stat and from 0.2 to 0.05 1/h in the De-stat. Apple pectin as a substrate was used in the chemostat experiments and apple pectin or birch xylan in the changestat experiments, in the presence of porcine mucin in all cases. The analyses were comprised of HPLC for organic acids, UPLC for amino acids, GC for gas composition, 16S-rDNA sequencing for microbial composition, and growth parameter calculations. It was shown that the abundance of most bacterial taxa was determined by the dilution rate on both substrates. Bacteroides ovatus, Bacteroides vulgatus, and Faecalibacterium were prevalent within the whole range of dilution rates. Akkermansia muciniphila and Ruminococcaceae UCG-013 were significantly enriched at D = 0.05 1/h, while Bacteroides caccae, Lachnospiraceae unclassified and Escherichia coli clearly preferred D = 0.2 1/h. In the chemostat cultures, the production of organic acids and gases from pectin was related to the dilution rate. The ratio of acetate, propionate and butyrate was 5:2:1 (D = 0.05 1/h) and 14:2:1 (D = 0.2 1/h). It was shown that the growth rate-related characteristics of the fecal microbiota were concise in both directions between D = 0.05 and 0.2 1/h. Reproducible adaptation of the fecal microbiota was shown in the continuous culture with a changing dilution rate: changestat. Consortia cultivation is a promising approach for research purposes and several biotechnological applications, including the production of multi-strain probiotics and fecal transplantation mixtures.}, }
@article {pmid32117313, year = {2020}, author = {Michael, H and Langel, SN and Miyazaki, A and Paim, FC and Chepngeno, J and Alhamo, MA and Fischer, DD and Srivastava, V and Kathayat, D and Deblais, L and Rajashekara, G and Saif, LJ and Vlasova, AN}, title = {Malnutrition Decreases Antibody Secreting Cell Numbers Induced by an Oral Attenuated Human Rotavirus Vaccine in a Human Infant Fecal Microbiota Transplanted Gnotobiotic Pig Model.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {196}, pmid = {32117313}, issn = {1664-3224}, support = {R01 AI099451/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Viral/blood ; Antibody-Producing Cells/*immunology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Germ-Free Life ; Humans ; Infant ; Intestines/immunology ; Malnutrition/*immunology ; Rotavirus/immunology ; Rotavirus Vaccines/*immunology ; Swine ; Vaccination ; Vaccines, Attenuated/immunology ; }, abstract = {Human rotavirus (HRV) is a leading cause of morbidity and mortality in children, especially in developing countries. Malnutrition is prevalent in these countries, which may contribute to the decreased oral vaccine efficacy, posing a concern for global health. Neonatal gnotobiotic (Gn) pigs closely resemble human infants in their anatomy, physiology, and outbred status and are a unique model to investigate malnutrition, oral live attenuated HRV (AttHRV) vaccination, and subsequent virulent HRV (VirHRV) challenge. We evaluated the impact of malnutrition on AttHRV vaccine efficacy and B cell immune responses in neonatal germfree (GF) or Gn pigs transplanted with human infant fecal microbiota (HIFM). Pigs were fed either deficient or sufficient bovine milk diets. Malnutrition did not significantly affect the serum and intestinal contents total or HRV-specific IgG and IgA antibody titers pre VirHRV challenge. However, HRV-specific IgG and IgA antibody secreting cells (ASCs) were reduced in blood or intestinal tissues following AttHRV vaccination and pre VirHRV challenge in deficient HIFM transplanted pigs. Furthermore, post-VirHRV challenge, deficient HIFM pigs had decreased total Ig and HRV-specific IgG and IgA antibody titers in serum or intestinal contents, in addition to decreased HRV-specific IgG and IgA ASCs in blood and ileum, compared with sufficient HIFM pigs. Our results indicate that deficient diet impairs B cell mucosal, and systemic immune responses following HRV vaccination, and challenge. The impaired immune responses contributed to the decreased protective efficacy of the AttHRV vaccine, suggesting that malnutrition may significantly reduce the effectiveness of oral HRV vaccines in children in developing countries.}, }
@article {pmid32117276, year = {2020}, author = {Horak, J and Nalos, L and Martinkova, V and Tegl, V and Vistejnova, L and Kuncova, J and Kohoutova, M and Jarkovska, D and Dolejsova, M and Benes, J and Stengl, M and Matejovic, M}, title = {Evaluation of Mesenchymal Stem Cell Therapy for Sepsis: A Randomized Controlled Porcine Study.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {126}, pmid = {32117276}, issn = {1664-3224}, mesh = {Animals ; Disease Models, Animal ; Mesenchymal Stem Cell Transplantation/*methods ; Random Allocation ; Sepsis/*therapy ; Swine ; }, abstract = {Background: Treatment with mesenchymal stem cells (MSCs) has elicited considerable interest as an adjunctive therapy in sepsis. However, the encouraging effects of experiments with MSC in rodents have not been adequately studied in large-animal models with better relevance to human sepsis. Objectives: Here, we aimed to assess safety and efficacy of bone marrow-derived MSCs in a clinically relevant porcine model of progressive peritonitis-induced sepsis. Methods: Thirty-two anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned into four groups (n = 8 per group): (1) sham-operated group (CONTROL); (2) sham-operated group treated with MSCs (MSC-CONTROL); (3) sepsis group with standard supportive care (SEPSIS); and (4) sepsis group treated with MSCs (MSC-SEPSIS). Peritoneal sepsis was induced by inoculating cultivated autologous feces. MSCs (1 × 10[6]/kg) were administered intravenously at 6 h after sepsis induction. Results: Before, 12, 18, and 24 h after the induction of peritonitis, we measured systemic, regional, and microvascular hemodynamics, multiple-organ functions, mitochondrial energy metabolism, systemic immune-inflammatory response, and oxidative stress. Administration of MSCs in the MSC-CONTROL group did not elicit any measurable acute effects. Treatment of septic animals with MSCs failed to mitigate sepsis-induced hemodynamic alterations or the gradual rise in Sepsis-related organ failure assessment scores. MSCs did not confer any protection against sepsis-mediated cellular myocardial depression and mitochondrial dysfunction. MSCs also failed to modulate the deregulated immune-inflammatory response. Conclusion: Intravenous administration of bone marrow-derived MSCs to healthy animals was well-tolerated. However, in this large-animal, clinically relevant peritonitis-induced sepsis model, MSCs were not capable of reversing any of the sepsis-induced disturbances in multiple biological, organ, and cellular systems.}, }
@article {pmid32117102, year = {2020}, author = {Tsigalou, C and Konstantinidis, T and Stavropoulou, E and Bezirtzoglou, EE and Tsakris, A}, title = {Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {50}, pmid = {32117102}, issn = {1664-302X}, abstract = {Recent advances in technology over the last decades have strived to elucidate the diverse and abundant ecosystem of the human microbiome. The intestinal microbiota represents a densely inhabited environment that offers a plethora of beneficial effects to the host's wellbeing. On the other hand, it can serve as a potential reservoir of Multi-Drug Resistant (MDR) bacteria and their antibiotic-resistant genes (ARgenes), which comprise the "gut resistome." ARgenes, like antibiotics, have been omnipresent in the environment for billions of years. In the context of the gut microbiome, these genes may conflate into exogenous MDR or emerge in commensals due to mutations or gene transfers. It is currently generally accepted that Antimicrobial Resistance (AMR) poses a serious threat to public health worldwide. It is of paramount importance that researchers focus on, amongst other parameters, elaborating strategies to manage the gut resistome, particularly focusing on the diminution of AMR. Potential interventions in the gut microbiome field by Fecal Microbiota Transplant (FMT) or functional foods are newly emerged candidates for the uprooting of MDR strains and restoring dysbiosis and resilience. Probiotic nutrition is thought to diminish gut colonization from pathobionts. Yet only a few studies have explored the effects of antibiotics use on the reservoir of AR genes and the demanding time for return to normal by gut microbiota-targeted strategies. Regular administration of probiotic bacteria has recently been linked to restoration of the gut ecosystem and decrease of the gut resistome and AR genes carriers. This review summarizes the latest information about the intestinal resistome and the intriguing methods of fighting against AMR through probiotic-based methods and gut microbial shifts that have been proposed. This study contains some key messages: (1) AMR currently poses a lethal threat to global health, and it is pivotal for the scientific community to do its utmost in fighting against it; (2) human gut microbiome research, within the last decade especially, seems to be preoccupied with the interface of numerous diseases and identifying a potential target for a variety of interventions; (3) the gut resistome, comprised of AR genesis, presents very early on in life and is prone to shifts due to the use of antibiotics or dietary supplements; and (4) future strategies involving functional foods seem promising for the battle against AMR through intestinal resistome diminution.}, }
@article {pmid32116985, year = {2019}, author = {Yang, D and Zhao, D and Ali Shah, SZ and Wu, W and Lai, M and Zhang, X and Li, J and Guan, Z and Zhao, H and Li, W and Gao, H and Zhou, X and Yang, L}, title = {Corrigendum: The Role of the Gut Microbiota in the Pathogenesis of Parkinson's Disease.}, journal = {Frontiers in neurology}, volume = {10}, number = {}, pages = {1412}, doi = {10.3389/fneur.2019.01412}, pmid = {32116985}, issn = {1664-2295}, abstract = {[This corrects the article DOI: 10.3389/fneur.2019.01155.].}, }
@article {pmid32115244, year = {2020}, author = {Neff, AS}, title = {Technical and Theoretic Limitations of the Experimental Evidence Supporting a Gut Bacterial Etiology in Mental Illness.}, journal = {Clinical therapeutics}, volume = {42}, number = {4}, pages = {e74-e81}, doi = {10.1016/j.clinthera.2020.02.002}, pmid = {32115244}, issn = {1879-114X}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Brain/physiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Mental Disorders/*microbiology ; Mice ; Probiotics/*therapeutic use ; }, abstract = {The impact of gut bacteria on the brain and behavior has become the subject of intense research. The brain is sensitive to biochemical and physiologic changes in the body, for example, changes in blood oxygenation or nutritional status. The collection of microorganisms residing within the digestive tract (the gut microbiome) is increasingly considered a major contributor to human physiology. These 2 considerations have led to the hypothesis that human psychology, including complex constructs like emotion and mental illness, could be influenced by the composition or function of gut bacteria. Five lines of evidence have been used to support the concept, including human correlational research, probiotic supplementation, antibiotic use, germ-free animal research, and fecal transplantation. Results from these experiments do not provide substantial support for the theory that complex human psychology is under the influence of gut bacteria. Placebo-controlled interventional research in humans, in particular fecal microbiota transplantation, will be required before a stronger conclusion can be reached.}, }
@article {pmid32114770, year = {2021}, author = {Jiménez-Avalos, JA and Arrevillaga-Boni, G and González-López, L and García-Carvajal, ZY and González-Avila, M}, title = {Classical methods and perspectives for manipulating the human gut microbial ecosystem.}, journal = {Critical reviews in food science and nutrition}, volume = {61}, number = {2}, pages = {234-258}, doi = {10.1080/10408398.2020.1724075}, pmid = {32114770}, issn = {1549-7852}, mesh = {Dysbiosis ; Ecosystem ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics ; }, abstract = {A healthy Human Gut Microbial Ecosystem (HGME) is a necessary condition for maintaining the orderly function of the whole body. Major alterations in the normal gut microbial composition, activity and functionality (dysbiosis) by an environmental or host-related disruptive event, can compromise metabolic, inflammatory, and neurological processes, causing disorders such as obesity, inflammatory bowel disease, colorectal cancer, and depressive episodes. The restore or the maintaining of the homeostatic balance of Gut Microbiota (GM) populations (eubiosis) is possible through diet, the use of probiotics, prebiotics, antibiotics, and even Fecal Microbiota Transplantation (FMT). Although these "classic methods" represent an effective and accepted way to modulate GM, the complexity of HGME requires new approaches to control it in a more appropriate way. Among the most promising emergent strategies for modulating GM are the use of engineered nanomaterials (metallic nanoparticles (NP), polymeric-NP, quantum dots, micelles, dendrimers, and liposomes); phagotherapy (i.e., phages linked with the CRISPR/Cas9 system), and the use of antimicrobial peptides, non-antibiotic drugs, vaccines, and immunoglobulins. Here we review the current state of development, implications, advantages, disadvantages, and perspectives of the different approaches for manipulating HGME.}, }
@article {pmid32110880, year = {2020}, author = {Sanchez-Rodriguez, E and Egea-Zorrilla, A and Plaza-Díaz, J and Aragón-Vela, J and Muñoz-Quezada, S and Tercedor-Sánchez, L and Abadia-Molina, F}, title = {The Gut Microbiota and Its Implication in the Development of Atherosclerosis and Related Cardiovascular Diseases.}, journal = {Nutrients}, volume = {12}, number = {3}, pages = {}, pmid = {32110880}, issn = {2072-6643}, mesh = {Animals ; Atherosclerosis/*microbiology/*pathology/prevention &amp; control/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Molecular Targeted Therapy ; Precision Medicine ; Probiotics/therapeutic use ; }, abstract = {The importance of gut microbiota in health and disease is being highlighted by numerous research groups worldwide. Atherosclerosis, the leading cause of heart disease and stroke, is responsible for about 50% of all cardiovascular deaths. Recently, gut dysbiosis has been identified as a remarkable factor to be considered in the pathogenesis of cardiovascular diseases (CVDs). In this review, we briefly discuss how external factors such as dietary and physical activity habits influence host-microbiota and atherogenesis, the potential mechanisms of the influence of gut microbiota in host blood pressure and the alterations in the prevalence of those bacterial genera affecting vascular tone and the development of hypertension. We will also be examining the microbiota as a therapeutic target in the prevention of CVDs and the beneficial mechanisms of probiotic administration related to cardiovascular risks. All these new insights might lead to novel analysis and CVD therapeutics based on the microbiota.}, }
@article {pmid32109968, year = {2020}, author = {Zhao, X and Jiang, Y and Xi, H and Chen, L and Feng, X}, title = {Exploration of the Relationship Between Gut Microbiota and Polycystic Ovary Syndrome (PCOS): a Review.}, journal = {Geburtshilfe und Frauenheilkunde}, volume = {80}, number = {2}, pages = {161-171}, pmid = {32109968}, issn = {0016-5751}, abstract = {Polycystic ovary syndrome (PCOS) is an endocrine and metabolic syndrome (MS) with a complex etiology, and its pathogenesis is not yet clear. In recent years, the correlation between gut microbiota (GM) and metabolic disease has become a hot topic in research, leading to a number of new ideas about the etiology and pathological mechanisms of PCOS. The literature shows that GM can cause insulin resistance, hyperandrogenism, chronic inflammation and metabolic syndrome (obesity, diabetes) and may contribute to the development of PCOS by influencing energy absorption, the pathways of short chain fatty acids (SCFA), lipopolysaccharides, choline and bile acids, intestinal permeability and the brain-gut axis. As part of the treatment of PCOS, fecal microbiota transplantation, supplementation with prebiotics and traditional Chinese medicine can be used to regulate GM and treat disorders. This article reviews possible mechanisms and treatment options for PCOS, based on methods which target the GM, and offers new ideas for the treatment of PCOS.}, }
@article {pmid32107829, year = {2020}, author = {Korula, A and Perumalla, S and Devasia, AJ and Abubacker, FN and Lakshmi, KM and Abraham, A and Mathews, V and Srivastava, A and Anandan, S and Veeraraghavan, B and George, B}, title = {Drug-resistant organisms are common in fecal surveillance cultures, predict bacteremia and correlate with poorer outcomes in patients undergoing allogeneic stem cell transplants.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {22}, number = {3}, pages = {e13273}, doi = {10.1111/tid.13273}, pmid = {32107829}, issn = {1399-3062}, mesh = {Adolescent ; Adult ; Bacteremia/*diagnosis/mortality ; Bacteria/classification/*drug effects/isolation &amp; purification ; Child ; Child, Preschool ; Diagnostic Screening Programs ; *Drug Resistance, Multiple, Bacterial ; Feces/*microbiology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Infant ; Male ; Middle Aged ; Outcome and Process Assessment, Health Care ; Retrospective Studies ; Sepsis/etiology/mortality ; Young Adult ; }, abstract = {BACKGROUND: With the increasing incidence of multidrug-resistant (MDR) organisms and high mortality rates associated with these infections, we describe the spectrum of the major drug-resistant pathogens identified in fecal surveillance, and re-visit the use of fecal surveillance in predicting infection with these organisms post-allogeneic stem cell transplant.<br><br>METHODS: Data from allogeneic stem cell transplant recipients with common drug-resistant strains of bacteria in fecal surveillance (Escherichia coli, Klebsiella spp., and Enterococcus spp.) were compared with recipients who did not have the same in fecal surveillance cultures. Baseline characteristics and post-transplant outcomes including similar drug resistance in blood cultures, severe sepsis, and 100-day transplant-related mortality were compared. Multivariate analysis using logistic regression model was used to determine independent predictors of outcome.<br><br>RESULTS: In 232 transplants, the prevalence of common drug-resistant isolates in fecal surveillance cultures was 57.7% (134 out of 232 patients-with a single isolate in 115 and &#x2265;2 isolates in the remaining 19 patients. A total of 164 drug-resistant isolates were obtained from 134 patients. Of the 164 isolates, 133 (81%) were positive for ESBL screening, 19 (11.5%) for carbapenem-resistant organisms (CRO) screening, 12 (7.3%) for VRE screening. Patients who had common drug-resistant pathogens detected in fecal surveillance have significantly higher subsequent blood culture positivity with drug resistance, as well as higher 100-day mortality. Factors influencing 100-day mortality included patient's age (P&#xa0;=&#xa0;.001), drug resistance positivity in blood (P&#xa0;<&#xa0;.001), drug resistance in fecal surveillance (P&#xa0;=&#xa0;.011), use of an alternate donor (other than fully matched sibling) (P&#xa0;<&#xa0;.001), GVHD grade 3-4 (P&#xa0;<&#xa0;.001), and severe sepsis (P&#xa0;<&#xa0;.001). On multivariate analysis, only use of an alternate donor (0.024), severe sepsis (P&#xa0;<&#xa0;.001), and grade 3-4 GVHD (P&#xa0;<&#xa0;.001) retained significance in predicting 100-day mortality.<br><br>CONCLUSION: Organisms resistant to 3rd generation cephalosporins are frequently seen on fecal surveillance in the pre-transplant setting and are associated with a higher incidence of drug-resistant organisms in subsequent blood cultures (not limited to the same drug resistance pattern as seen in fecal surveillance). Drug-resistant organisms in fecal surveillance are associated with poorer outcomes following allogeneic stem cell transplant and may be used as a guide to identify patients at risk of subsequently developing a drug-resistant organism in blood.}, }
@article {pmid32107473, year = {2020}, author = {König, J and Brummer, RJ}, title = {Faecal microbiota transplantation in IBS - new evidence for success?.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {17}, number = {4}, pages = {199-200}, pmid = {32107473}, issn = {1759-5053}, mesh = {Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome ; }, }
@article {pmid32106123, year = {2020}, author = {Yan, PG and Li, JN}, title = {Advances in the understanding of the intestinal micro-environment and inflammatory bowel disease.}, journal = {Chinese medical journal}, volume = {133}, number = {7}, pages = {834-841}, pmid = {32106123}, issn = {2542-5641}, mesh = {Colitis/microbiology ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Humans ; Inflammatory Bowel Diseases/*microbiology ; }, abstract = {The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes, the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease (IBD). In the past few years, with the advances in the understanding of microbiome, its metabolites and further application of next generation sequencing, analysis of dynamic alteration of gut micro-environment was realized, which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis status. The subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential therapy. In this review, we will summarize the recent knowledge about multi-dimensional dysbiosis, the inter-action between fungus and bacteria under inflamed mucosa, and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD.}, }
@article {pmid32104162, year = {2020}, author = {Cheng, YW and Fischer, M}, title = {Fecal Microbiota Transplantation: Redefining Surgical Management of Refractory Clostridium difficile Infection.}, journal = {Clinics in colon and rectal surgery}, volume = {33}, number = {2}, pages = {92-97}, pmid = {32104162}, issn = {1531-0043}, abstract = {Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a diseased individual for therapeutic purposes. It has a clearly defined role in the treatment of recurrent Clostridium difficile (reclassified as " Clostridioides difficile ") infection (CDI), with cure rates over 90% and decreased rates of subsequent recurrence compared with anti-CDI antibiotics. There is emerging evidence that FMT is also effective in the treatment of severe and fulminant CDI, with associated decreases in mortality and colectomy rates compared with standard antibiotic therapy. FMT shows promise as salvage therapy for critically-ill CDI patients refractory to maximum medical therapy and not deemed to be surgical candidates. FMT should be considered early in the course of severe CDI and should be delivered immediately in patients with signs of refractory CDI. Expansion of FMT's use along the spectrum of CDI severity has potential to decrease associated rates of mortality and colectomy.}, }
@article {pmid32104160, year = {2020}, author = {Baker, SJ and Chu, DI}, title = {Physical, Laboratory, Radiographic, and Endoscopic Workup for Clostridium difficile Colitis.}, journal = {Clinics in colon and rectal surgery}, volume = {33}, number = {2}, pages = {82-86}, pmid = {32104160}, issn = {1531-0043}, abstract = {Clostridium (reclassified as " Clostridioides ") difficile colitis is a common nosocomial infection associated with increased morbidity and mortality. Like many clinical encounters, a focused history and physical examination will help to guide initial management. Further laboratory testing will assist with diagnosis through stool studies, and blood tests, such as white blood cell counts and serum creatinine, can help to stratify patients into illness severity groups for treatment decisions. Radiographic evaluation can be helpful in patients with severe disease and concern for complicated colitis. Endoscopic evaluation should be carefully considered in patients with suspected mucosal injury secondary to infections and plays a role when an alternative diagnosis is suspected. Treatment options depend on the clinical presentation and can range from antibiotic therapy to emergent surgery to fecal transplantation for recurrent episodes. Care for these patients is often challenging, but through a systemic workup the appropriate treatment may be delivered.}, }
@article {pmid32102925, year = {2020}, author = {Barbara, G and Ianiro, G}, title = {Faecal microbial transplantation in IBS: ready for prime time?.}, journal = {Gut}, volume = {69}, number = {5}, pages = {795-796}, doi = {10.1136/gutjnl-2019-320411}, pmid = {32102925}, issn = {1468-3288}, mesh = {Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome ; *Microbiota ; }, }
@article {pmid32101664, year = {2020}, author = {Peled, JU and Gomes, ALC and Devlin, SM and Littmann, ER and Taur, Y and Sung, AD and Weber, D and Hashimoto, D and Slingerland, AE and Slingerland, JB and Maloy, M and Clurman, AG and Stein-Thoeringer, CK and Markey, KA and Docampo, MD and Burgos da Silva, M and Khan, N and Gessner, A and Messina, JA and Romero, K and Lew, MV and Bush, A and Bohannon, L and Brereton, DG and Fontana, E and Amoretti, LA and Wright, RJ and Armijo, GK and Shono, Y and Sanchez-Escamilla, M and Castillo Flores, N and Alarcon Tomas, A and Lin, RJ and Yáñez San Segundo, L and Shah, GL and Cho, C and Scordo, M and Politikos, I and Hayasaka, K and Hasegawa, Y and Gyurkocza, B and Ponce, DM and Barker, JN and Perales, MA and Giralt, SA and Jenq, RR and Teshima, T and Chao, NJ and Holler, E and Xavier, JB and Pamer, EG and van den Brink, MRM}, title = {Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.}, journal = {The New England journal of medicine}, volume = {382}, number = {9}, pages = {822-834}, pmid = {32101664}, issn = {1533-4406}, support = {1R01CA228308-01/CA/NCI NIH HHS/United States ; P01-AG052359 (Project 2)/AG/NIA NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 AI137269-01//National Institute of Allergy and Infectious Diseases/International ; K08HL143189-01A1/HL/NHLBI NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; P01-CA023766 (Project 4)/CA/NCI NIH HHS/United States ; KL2 TR001115-03/TR/NCATS NIH HHS/United States ; 17K09945//Japan Society for the Promotion of Science/International ; 17H04206//Japan Society for the Promotion of Science/International ; 2016-013/US/United States/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; 1R01HL124112-01A/HL/NHLBI NIH HHS/United States ; R01 AI032135/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01CA203950-01/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; KL2 TR001115/TR/NCATS NIH HHS/United States ; R01-HL125571/HL/NHLBI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; R01-HL125571/CA/NCI NIH HHS/United States ; R01 AI100288/AI/NIAID NIH HHS/United States ; T32 AI100851/AI/NIAID NIH HHS/United States ; U01 AI124275/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 CA203950/CA/NCI NIH HHS/United States ; R01-HL123340/HL/NHLBI NIH HHS/United States ; 2P30AG028716-11/AG/NIA NIH HHS/United States ; R01 AI032135/NH/NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; 1R01CA228358-01/CA/NCI NIH HHS/United States ; AI095706//National Institute of Allergy and Infectious Diseases/International ; }, mesh = {Adult ; Biodiversity ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Hematopoietic Stem Cell Transplantation/*mortality ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Survival Analysis ; Transplantation, Homologous/mortality ; }, abstract = {BACKGROUND: Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable.<br><br>METHODS: The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death.<br><br>RESULTS: We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival.<br><br>CONCLUSIONS: Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.).}, }
@article {pmid32100696, year = {2020}, author = {Perez-Zetune, V and Bialek, SR and Montgomery, SP and Stillwaggon, E}, title = {Congenital Chagas Disease in the United States: The Effect of Commercially Priced Benznidazole on Costs and Benefits of Maternal Screening.}, journal = {The American journal of tropical medicine and hygiene}, volume = {102}, number = {5}, pages = {1086-1089}, pmid = {32100696}, issn = {1476-1645}, mesh = {Chagas Disease/complications/*congenital/drug therapy/epidemiology ; Cost Savings/economics/methods/statistics &amp; numerical data ; Cost-Benefit Analysis ; Female ; Humans ; Infectious Disease Transmission, Vertical/economics/statistics &amp; numerical data ; Mass Screening/*economics/methods ; Nitroimidazoles/economics/*therapeutic use ; Pregnancy ; Pregnancy Complications, Parasitic/diagnosis/*drug therapy/economics ; Trypanocidal Agents/economics/*therapeutic use ; United States/epidemiology ; }, abstract = {Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors, and through transfusions, transplants, insect feces in food, and mother to child during gestation. An estimated 30% of infected persons will develop lifelong, potentially fatal cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment for Chagas disease in the United States, including the cost of commercially available benznidazole. We compare costs of testing and treatment for mothers and infants with the lifetime societal costs without testing and consequent morbidity and mortality due to lack of treatment or late treatment. We constructed a decision-analytic model, using one tree that shows the combined costs for every possible mother-child pairing. Savings per birth in a targeted screening program are $1,314, and with universal screening, $105 per birth. At current screening costs, universal screening results in $420 million in lifetime savings per birth-year cohort. We found that a congenital Chagas screening program in the United States is cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence greater than 0.06% compared with no screening program.}, }
@article {pmid32100127, year = {2020}, author = {Chen, K and Fu, Y and Wang, Y and Liao, L and Xu, H and Zhang, A and Zhang, J and Fan, L and Ren, J and Fang, B}, title = {Therapeutic Effects of the In Vitro Cultured Human Gut Microbiota as Transplants on Altering Gut Microbiota and Improving Symptoms Associated with Autism Spectrum Disorder.}, journal = {Microbial ecology}, volume = {80}, number = {2}, pages = {475-486}, doi = {10.1007/s00248-020-01494-w}, pmid = {32100127}, issn = {1432-184X}, support = {81770558//National Natural Science Foundation of China/ ; 3502Z20149031//Xiamen Joint Projects for Major Diseases/ ; }, mesh = {Animals ; Autism Spectrum Disorder/*therapy ; Bacteria/*metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {Autism spectrum disorder (ASD) is a brain-based neurodevelopmental disorder characterized by behavioral abnormalities. Accumulating studies show that the gut microbiota plays a vital role in the pathogenesis of ASD, and gut microbiota transplantation (GMT) is a promising technique for the treatment of ASD. In clinical applications of GMT, it is challenging to obtain effective transplants because of the high costs of donor selection and heterogeneity of donors' gut microbiota, which can cause different clinical responses. In vitro batch culture is a fast, easy-to-operate, and repeatable method to culture gut microbiota. Thus, the present study investigates the feasibility of treating ASD with in vitro cultured gut microbiota as transplants. We cultured gut microbiota via the in vitro batch culture method and performed GMT in the maternal immune activation (MIA)-induced ASD mouse model with original donor microbiota and in vitro cultured microbiota. Open field, three-chamber social, marble burying, and self-grooming tests were used for behavioral improvement assessment. Serum levels of chemokines were detected. Microbial total DNA was extracted from mouse fecal samples, and 16S rDNA was sequenced using Illumina. Our results showed that GMT treatment with original and cultured donor gut microbiota significantly ameliorated anxiety-like and repetitive behaviors and improved serum levels of chemokines including GRO-α (CXCL1), MIP-1α (CCL3), MCP-3 (CCL7), RANTES (CCL5), and Eotaxin (CCL11) in ASD mice. Meanwhile, the gut microbial communities of the two groups that received GMT treatment were changed compared with the ASD mice groups. In the group treated with in vitro cultured donor gut microbiota, there was a significant decrease in the relative abundance of key differential taxa, including S24-7, Clostridiaceae, Prevotella_other, and Candidatus Arthromitus. The relative abundance of these taxa reached close to the level of healthy mice. Prevotella_other also decreased in the group treated with original donor gut microbiota, with a significant increase in Ruminococcaceae and Oscillospira. The present study demonstrated that GMT with in vitro cultured microbiota also improved behavioral abnormalities and chemokine disorders in an ASD mouse model compared with GMT with original donor gut microbiota. In addition, it significantly modified several key differential taxa in gut microbial composition.}, }
@article {pmid32099702, year = {2020}, author = {Ueckermann, V and Hoosien, E and De Villiers, N and Geldenhuys, J}, title = {Fecal Microbial Transplantation for the Treatment of Persistent Multidrug-Resistant Klebsiella pneumoniae Infection in a Critically Ill Patient.}, journal = {Case reports in infectious diseases}, volume = {2020}, number = {}, pages = {8462659}, pmid = {32099702}, issn = {2090-6625}, abstract = {Dysbiosis of the microbiome is a common finding in critically ill patients, who receive broad-spectrum antibiotics and various forms of organ support. Multidrug-resistant (MDR) organisms are a growing threat in all areas of medicine, but most markedly in the critically ill, where there is both loss of host defences and widespread use of broad spectrum antibiotics. We present a case of a critically ill patient with persistent MDR Klebsiella pneumoniae infection, successfully treated with fecal microbiota transplantation (FMT), using stool of a rigorously-screened, healthy donor. FMT for Clostridium difficile colitis has been well described in the literature and is an established therapy for recurrent infections with Clostridium difficile. The use of FMT for other multidrug-resistant organisms is less frequently described, particularly in the context of critically ill patients. In our case, we have culture-documented clearance of the MDR Klebsiella pneumoniae form a patient of FMT.}, }
@article {pmid32098515, year = {2020}, author = {Southwell, BR}, title = {Treatment of childhood constipation: a synthesis of systematic reviews and meta-analyses.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {14}, number = {3}, pages = {163-174}, doi = {10.1080/17474124.2020.1733974}, pmid = {32098515}, issn = {1747-4132}, mesh = {Child ; Constipation/*therapy ; Humans ; Practice Guidelines as Topic ; }, abstract = {Introduction: Constipation occurs in many children and can become chronic. Many grow out of it but for one third, it continues into adulthood. For most patients, there is no identifiable organic disorder and it is classified as functional constipation.Areas covered: In 2016, treatment of childhood constipation was extensively reviewed by Rome IV. This review covers meta-analyses and evidence for treatment of paediatric constipation since 2016 and new emerging treatments.Expert opinion: Since 2016, meta-analyses conclude 1) fibre should be included in a normal diet, but further supplementation does not improve constipation; 2) probiotics may increase stool frequency in children, but evidence from larger RCTs is needed; 3) comparing laxatives, polyethylene glycol (PEG) is superior to placebo, lactulose and milk of magnesia, and 4) appendix stomas are effective and should be considered before surgery. Emerging areas of study include food intolerance, electrical stimulation and faecal microbiota transplant. For research, outcome measures need standardising to allow comparison between studies and allow meta-analyses. To assist this, validated GI instruments have been developed by Rome IV and PedsQl.}, }
@article {pmid32098421, year = {2020}, author = {Gabay, O and Vicenty, J and Smith, D and Tiffany, L and Ascher, J and Curry, T and Dennis, J and Clouse, KA}, title = {Using a Model of Germ-Free Animals to Study the Impact of Gut Microbiome in Research: A Step by Step Sterility Setting and Management.}, journal = {Methods and protocols}, volume = {3}, number = {1}, pages = {}, pmid = {32098421}, issn = {2409-9279}, abstract = {The particularly unique composition of the gut microbiota has the potential to influence the health or disease status of animal and human hosts. Altering the homeostasis of the host-bacteria could lead to changes in gut flora that result in disease or activation of a specific immunological response, which could explain the variations observed in patient responses to current therapies. A standardized model is crucial for studying the influence of the gut microbiota on therapeutic modalities. A step by step mouse model and sterility management system that compares a control strain of C57BL/6 mice to the established C57BL/6 germ-free (GF) strain has been developed. The GF BL/6 mouse phenotype is well established, and the anatomical differences between the GF and control mice were evident in this model. This method could be applied to research studies investigating the microbiome impact, the response to various therapies, or disease transfer via fecal transplants. A standardized sterility maintenance method is crucial in this context.}, }
@article {pmid32089675, year = {2020}, author = {Mazzawi, T and Eikrem, &#xd8; and Lied, GA and Hausken, T}, title = {Abnormal Uroguanylin Immunoreactive Cells Density in the Duodenum of Patients with Diarrhea-Predominant Irritable Bowel Syndrome Changes following Fecal Microbiota Transplantation.}, journal = {Gastroenterology research and practice}, volume = {2020}, number = {}, pages = {3520686}, pmid = {32089675}, issn = {1687-6121}, abstract = {Altered densities of enteroendocrine cells play an important role in patients with irritable bowel syndrome (IBS). Uroguanylin activates guanylate cyclase-C to regulate intestinal electrolyte and water transport. Aim. To quantify uroguanylin immunoreactive cells density in the duodenum of diarrhea-predominant IBS (IBS-D) patients compared to controls and to investigate the effect of fecal microbiota transplantation (FMT) on these cell densities. Method. Twelve patients with IBS-D according to Rome III criteria were included. The cause was identified as post infectious (PI, n = 6) or idiopathic (n = 6). They completed the IBS-symptom questionnaire before and 3 weeks after FMT. Thirty grams of fresh feces donated from healthy relatives were diluted with 60 ml normal saline and instilled via endoscope into the duodenum. Biopsies were taken from the patients' duodenum before and 3 weeks after FMT. Duodenal biopsies taken from eight healthy controls were also included. The biopsies were immunostained for uroguanylin and quantified using computerized image analysis. Results. Uroguanylin immunoreactive cells were found both in duodenal villi and crypts in both controls and IBS-D patients. The densities of uroguanylin immunoreactive cells were significantly lower in the villi (P < 0.0001) and higher in the crypts (P < 0.0001) for the patients than the controls. Following FMT, the densities of uroguanylin immunoreactive cells for the total group and idiopathic subgroup decreased significantly in the duodenal crypts (P = 0.049 and 0.04, respectively) but not in the villi. No significant changes were shown in the PI-IBS subgroups. The cells density in only the crypts correlated with diarrhea (r = 0.97, P = 0.001) and bloating (r = -0.91, P = 0.01) in the PI-IBS subgroup before FMT and with abdominal pain (r = 0.63, P = 0.03) in the total group of IBS-D patients after FMT. Conclusion. Altered uroguanylin immunoreactive cells density was found in IBS-D patients compared to controls. Changes in these cells density following FMT correlated with IBS symptoms (diarrhea, bloating, and abdominal pain).}, }
@article {pmid32089055, year = {2020}, author = {Chen, EB and Shapiro, KE and Wun, K and Kuntz, T and Theriault, BR and Nooromid, MJ and Leone, VA and Harris, KG and Jiang, Q and Spedale, M and Xiong, L and Gilbert, JA and Chang, EB and Ho, KJ}, title = {Microbial Colonization of Germ-Free Mice Restores Neointimal Hyperplasia Development After Arterial Injury.}, journal = {Journal of the American Heart Association}, volume = {9}, number = {5}, pages = {e013496}, pmid = {32089055}, issn = {2047-9980}, support = {R01 DK111848/DK/NIDDK NIH HHS/United States ; U01 DK106786/DK/NIDDK NIH HHS/United States ; P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 GM062344/GM/NIGMS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; F32 DK113743/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; K08 HL130601/HL/NHLBI NIH HHS/United States ; R01 NR015446/NR/NINR NIH HHS/United States ; R01 DK097268/DK/NIDDK NIH HHS/United States ; K01 DK111785/DK/NIDDK NIH HHS/United States ; R03 HD095056/HD/NICHD NIH HHS/United States ; R34 HL136991/HL/NHLBI NIH HHS/United States ; T32 HL094293/HL/NHLBI NIH HHS/United States ; R56 DK102872/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Carotid Arteries/*pathology ; Carotid Artery Injuries/*microbiology/*pathology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Germ-Free Life ; Hyperplasia ; Male ; Mice, Inbred C57BL ; *Neointima ; }, abstract = {Background The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. Methods and Results We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age-, sex-, and strain-matched germ-free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ-free cohorts served as comparison groups. Conclusions Germ-free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.}, }
@article {pmid32083498, year = {2020}, author = {Lopetuso, LR and Ianiro, G and Allegretti, JR and Bibbò, S and Gasbarrini, A and Scaldaferri, F and Cammarota, G}, title = {Fecal transplantation for ulcerative colitis: current evidence and future applications.}, journal = {Expert opinion on biological therapy}, volume = {20}, number = {4}, pages = {343-351}, doi = {10.1080/14712598.2020.1733964}, pmid = {32083498}, issn = {1744-7682}, mesh = {Colitis, Ulcerative/pathology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Interleukin-1/metabolism ; Randomized Controlled Trials as Topic ; }, abstract = {Introduction: Established evidence suggests that gut microbiota plays a role in ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is clearly recognized as a highly effective treatment for patients with recurrent Clostridium difficile infection and has been investigated also in patients with UC, with promising results.Areas covered: Literature review was performed to select publications concerning current evidence on the role of gut microbiota in the pathogenesis of UC, and on the effectiveness of FMT in this disorder.Expert opinion: The randomized controlled trials published investigating the use of FMT suggested a potential role for FMT in the treatment of mild to moderate UC. However, given several unanswered questions regarding donor selection, dose, route of administration and duration of therapy, this is not yet recommended as a viable therapy option. FMT has allowed for more in depth investigation with regards to the role the gut microbiota may be playing in UC. This knowledge is critical to identifying where FMT may appropriately fit in the UC treatment paradigm. As our understanding of the role the microbiome plays in this chronic disease, FMT, and then eventually defined microbes, will hopefully serve in a complementary role to conventional IBD therapies.}, }
@article {pmid32080996, year = {2020}, author = {Bouza, E and Aguado, JM and Alcalá, L and Almirante, B and Alonso-Fernández, P and Borges, M and Cobo, J and Guardiola, J and Horcajada, JP and Maseda, E and Mensa, J and Merchante, N and Muñoz, P and Pérez Sáenz, JL and Pujol, M and Reigadas, E and Salavert, M and Barberán, J}, title = {Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spanish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR).}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {33}, number = {2}, pages = {151-175}, pmid = {32080996}, issn = {1988-9518}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*diagnosis/*drug therapy ; Continuity of Patient Care ; Cost-Benefit Analysis ; Diarrhea/microbiology ; Feces/microbiology ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Probiotics/therapeutic use ; Secondary Prevention ; Societies, Medical/standards ; Spain ; Specimen Handling/methods ; }, abstract = {This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.}, }
@article {pmid32079318, year = {2020}, author = {Pilmis, B and Le Monnier, A and Zahar, JR}, title = {Gut Microbiota, Antibiotic Therapy and Antimicrobial Resistance: A Narrative Review.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, pmid = {32079318}, issn = {2076-2607}, abstract = {Antimicrobial resistance is a major concern. Epidemiological studies have demonstrated direct relationships between antibiotic consumption and emergence/dissemination of resistant strains. Within the last decade, authors confounded spectrum activity and ecological effects and did not take into account several other factors playing important roles, such as impact on anaerobic flora, biliary elimination and sub-inhibitory concentration. The ecological impact of antibiotics on the gut microbiota by direct or indirect mechanisms reflects the breaking of the resistance barrier to colonization. To limit the impact of antibiotic therapy on gut microbiota, consideration of the spectrum of activity and route of elimination must be integrated into the decision. Various strategies to prevent (antimicrobial stewardship, action on residual antibiotics at colonic level) or cure dysbiosis (prebiotic, probiotic and fecal microbiota transplantation) have been introduced or are currently being developed.}, }
@article {pmid32078714, year = {2020}, author = {Luo, Y and Tixier, EN and Grinspan, AM}, title = {Fecal Microbiota Transplantation for Clostridioides difficile in High-Risk Older Adults Is Associated with Early Recurrence.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {12}, pages = {3647-3651}, pmid = {32078714}, issn = {1573-2568}, mesh = {Aged ; Clostridioides difficile/*isolation &amp; purification ; *Clostridium Infections/diagnosis/physiopathology/therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Follow-Up Studies ; Humans ; Immunocompromised Host ; *Inflammatory Bowel Diseases/diagnosis/epidemiology ; Male ; Recurrence ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Severity of Illness Index ; Time ; Treatment Outcome ; United States/epidemiology ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI). CDI disproportionately affects the elderly; however, there is a paucity of data on FMT effectiveness in older adults, especially subpopulations at highest risk for CDI-related morbidity and mortality.<br><br>AIM: To assess the efficacy and safety of FMT for CDI in older adults.<br><br>METHODS: A retrospective, long-term follow-up study was performed. The high-risk subpopulation included patients who were immunocompromised, patients with inflammatory bowel disease, and patients presenting with severe or fulminant colitis. Outcome measures included primary cure rates, early (<&#x2009;12&#xa0;weeks) and late (>&#x2009;12&#xa0;weeks) recurrence rates, adverse events, and subgroup analysis of higher-risk populations.<br><br>RESULTS: Our cohort included 75 patients (72% female) with a mean age of 76.4 and Charlson comorbidity index score of 5.4. There were 34 patients in our higher-risk subpopulation as defined above with an adjusted recurrence rate of 32.1%. FMT was performed for severe or fulminant disease in 30.6% of patients with a 3-month survival rate of 73.9%. Overall, the adjusted primary cure rate was 67.2% and the adjusted CDI recurrence was 29.9% in our cohort (90% of recurrences occurred early). Most adverse events in our study were rehospitalizations for recurrent CDI.<br><br>CONCLUSION: Compared with previous studies of FMT efficacy, our cohort had a lower primary cure rate and higher CDI recurrence rate than previously reported, likely driven by our higher-risk subpopulations. Nevertheless, FMT should be considered early to prevent progression of CDI severity and recurrence, especially in patients who present with severe and fulminant disease.}, }
@article {pmid32078445, year = {2020}, author = {Yan, X and Jin, J and Su, X and Yin, X and Gao, J and Wang, X and Zhang, S and Bu, P and Wang, M and Zhang, Y and Wang, Z and Zhang, Q}, title = {Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension.}, journal = {Circulation research}, volume = {126}, number = {7}, pages = {839-853}, doi = {10.1161/CIRCRESAHA.119.316394}, pmid = {32078445}, issn = {1524-4571}, mesh = {Animals ; Arachidonic Acid/metabolism ; Bacteroides fragilis/physiology ; Blood Pressure/*physiology ; Corticosterone/*biosynthesis/blood ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Hypertension/etiology/microbiology/*physiopathology ; Intestines/*chemistry/drug effects/microbiology ; Metabolomics/methods ; Rats, Wistar ; Sodium Chloride, Dietary/adverse effects ; }, abstract = {RATIONALE: High-salt diet is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated.<br><br>OBJECTIVE: To reveal the roles and mechanisms of intestinal flora in hSIH development.<br><br>METHODS AND RESULTS: The abovementioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture, and fecal microbiota transplantation. We found that high-salt diet induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, whereas the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism, and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis could inhibit the production of intestinal-derived corticosterone induced by high-salt diet through its metabolite arachidonic acid.<br><br>CONCLUSIONS: hSIH could be transferred by fecal microbiota transplantation, indicating the pivotal roles of intestinal flora in hSIH development. High-salt diet reduced the levels of B fragilis and arachidonic acid in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.}, }
@article {pmid32076497, year = {2020}, author = {Hazel, K and O'Connor, A}, title = {Emerging treatments for inflammatory bowel disease.}, journal = {Therapeutic advances in chronic disease}, volume = {11}, number = {}, pages = {2040622319899297}, pmid = {32076497}, issn = {2040-6223}, abstract = {Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation, a relapsing and remitting clinical course, requirement for lifelong medication and often, significant morbidity. While multiple effective therapeutic options exist for the treatment of IBD, a proportion of patients will either fail to respond or lose response to therapy. Advances in therapeutics, such as the gut-specific anti-integrins, now offer patients an alternative option to systemic immunosuppression. Anti-interleukin 12 (anti-IL-12)/IL-23 agents offer new and effective treatment options for CD, while the oral small molecules now offer an oral alternative for the treatment of moderate-to-severe disease, previously requiring subcutaneous injection or intravenous infusion. Alternatives to pharmacological treatment such as stem-cell transplant and faecal microbiota transplant are also showing some promise in the treatment of both CD and UC.}, }
@article {pmid32076145, year = {2020}, author = {Lavelle, A and Sokol, H}, title = {Gut microbiota-derived metabolites as key actors in inflammatory bowel disease.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {17}, number = {4}, pages = {223-237}, pmid = {32076145}, issn = {1759-5053}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Fatty Acids, Volatile/physiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/metabolism/microbiology ; Humans ; Inflammatory Bowel Diseases/diagnosis/metabolism/*microbiology/therapy ; Metabolomics/methods ; Probiotics/therapeutic use ; Tryptophan/metabolism ; }, abstract = {A key role of the gut microbiota in the establishment and maintenance of health, as well as in the pathogenesis of disease, has been identified over the past two decades. One of the primary modes by which the gut microbiota interacts with the host is by means of metabolites, which are small molecules that are produced as intermediate or end products of microbial metabolism. These metabolites can derive from bacterial metabolism of dietary substrates, modification of host molecules, such as bile acids, or directly from bacteria. Signals from microbial metabolites influence immune maturation, immune homeostasis, host energy metabolism and maintenance of mucosal integrity. Alterations in the composition and function of the microbiota have been described in many studies on IBD. Alterations have also been described in the metabolite profiles of patients with IBD. Furthermore, specific classes of metabolites, notably bile acids, short-chain fatty acids and tryptophan metabolites, have been implicated in the pathogenesis of IBD. This Review aims to define the key classes of microbial-derived metabolites that are altered in IBD, describe the pathophysiological basis of these associations and identify future targets for precision therapeutic modulation.}, }
@article {pmid32075742, year = {2020}, author = {Yang, C and Mogno, I and Contijoch, EJ and Borgerding, JN and Aggarwala, V and Li, Z and Siu, S and Grasset, EK and Helmus, DS and Dubinsky, MC and Mehandru, S and Cerutti, A and Faith, JJ}, title = {Fecal IgA Levels Are Determined by Strain-Level Differences in Bacteroides ovatus and Are Modifiable by Gut Microbiota Manipulation.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {3}, pages = {467-475.e6}, pmid = {32075742}, issn = {1934-6069}, support = {R01 DK123749/DK/NIDDK NIH HHS/United States ; R01 DK112296/DK/NIDDK NIH HHS/United States ; F30 CA235963/CA/NCI NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 GM108505/GM/NIGMS NIH HHS/United States ; F31 DK112679/DK/NIDDK NIH HHS/United States ; P50 AT008661/AT/NCCIH NIH HHS/United States ; S10 OD018522/OD/NIH HHS/United States ; S10 OD026880/OD/NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; P01 AI061093/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; B-Lymphocytes/immunology ; Bacteroides/*classification/immunology ; CD4-Positive T-Lymphocytes/immunology ; *Feces ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Immunoglobulin A/*immunology ; Intestine, Large/*immunology/microbiology ; Mice ; Mice, Inbred C57BL ; }, abstract = {Fecal IgA production depends on colonization by a gut microbiota. However, the bacterial strains that drive gut IgA production remain largely unknown. Here, we assessed the IgA-inducing capacity of a diverse set of human gut microbial strains by monocolonizing mice with each strain. We identified Bacteroides ovatus as the species that best induced gut IgA production. However, this induction varied bimodally across different B. ovatus strains. The high IgA-inducing B. ovatus strains preferentially elicited more IgA production in the large intestine through the T cell-dependent B cell-activation pathway. Remarkably, a low-IgA phenotype in mice could be robustly and consistently converted into a high-IgA phenotype by transplanting a multiplex cocktail of high IgA-inducing B. ovatus strains but not individual ones. Our results highlight the critical importance of microbial strains in driving phenotype variation in the mucosal immune system and provide a strategy to robustly modify a gut immune phenotype, including IgA production.}, }
@article {pmid32075113, year = {2020}, author = {Knobbe, TJ and Douwes, RM and Kremer, D and Swarte, JC and Eisenga, MF and Gomes-Neto, AW and van Londen, M and Peters, FTM and Blokzijl, H and Nolte, IM and Hendriks, WH and Harmsen, HJM and Bakker, SJL}, title = {Altered Gut Microbial Fermentation and Colonization with Methanobrevibacter smithii in Renal Transplant Recipients.}, journal = {Journal of clinical medicine}, volume = {9}, number = {2}, pages = {}, pmid = {32075113}, issn = {2077-0383}, abstract = {Renal transplant recipients (RTRs) often suffer from posttransplant diarrhea. The observed dysbiosis in RTR may influence the fermentation processes in the gut. In this study, we aimed to investigate whether fermentation differs between RTRs and healthy controls (HCs), by measuring breath H2 and CH4 concentrations. Additionally, we determined the fecal presence of the methanogen Methanobrevibacter smithii (M. smithii), which plays a main role in the process of methanogenesis. Data from the TransplantLines Biobank and Cohort Study (NCT03272841) was used. A total of 142 RTRs and 77 HCs were included. Breath H2 concentrations in RTRs were not significantly different from HCs. Breath CH4 concentrations in RTRs were significantly lower compared with HCs (median [interquartile range (IQR)] 7.5 [3.9-10.6] ppm vs. 16.0 [8.0-45.5] ppm, p < 0.001). M. smithii was less frequently present in the feces of RTRs compared to HCs (28.6% vs. 86.4% resp., p < 0.001). Our findings regarding the altered methanogenesis in the gut of RTRs show similarities with previous results in inflammatory bowel disease patients. These findings provide novel insight into the alterations of fermentation after renal transplantation, which may contribute to understanding the occurrence of posttransplant diarrhea.}, }
@article {pmid32071279, year = {2020}, author = {Madhusoodanan, J}, title = {News Feature: Editing the microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {7}, pages = {3345-3348}, pmid = {32071279}, issn = {1091-6490}, mesh = {Bacteria/*genetics/metabolism ; Bacteriophages/physiology ; Clostridioides difficile/physiology/virology ; Clostridium Infections/*microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Phage Therapy ; Plasmids/genetics/metabolism ; }, }
@article {pmid32068668, year = {2020}, author = {Rentsch, KM}, title = {Drug Exposure in Newborns: Effect of Selected Drugs Prescribed to Mothers During Pregnancy and Lactation.}, journal = {Therapeutic drug monitoring}, volume = {42}, number = {2}, pages = {255-263}, doi = {10.1097/FTD.0000000000000747}, pmid = {32068668}, issn = {1536-3694}, mesh = {Anti-Retroviral Agents/*pharmacokinetics ; Anticonvulsants/*pharmacokinetics ; Breast Feeding ; Dose-Response Relationship, Drug ; Female ; Fetal Blood/chemistry ; Humans ; Immunosuppressive Agents/*pharmacokinetics ; Infant, Newborn ; Meconium/chemistry ; Milk, Human/chemistry/*metabolism ; Placenta/metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects/*metabolism ; }, abstract = {The number of newborns exposed to therapeutic drugs during pregnancy is growing because of the increased use of drugs during pregnancy. In recent years, advances in our understanding of drug placental transfer have augmented the likelihood of a healthy baby in mothers with chronic diseases needing drug therapy. Globally, for example, more than 1.4 million pregnancies in 2015 have been burdened with antiretroviral drugs due to an increasing number of HIV-positive women treated with these drugs, particularly in low- and middle-income countries. In most cases, the fetus is exposed to much higher drug doses in utero than the newborn nursed by the mother. Drug transfer through the placenta takes place by passive diffusion, active transport, or facilitated transport, and drug concentrations in the fetal circulation may be comparable to that in the mother's blood concentration. The excretion of drugs into breastmilk predominantly occurs by passive diffusion, allowing only the non-protein-bound fraction of the blood drug concentration to penetrate. Drug agencies in the United States and Europe highly recommend performing clinical trials in pregnant or breastfeeding women. However, only a few drugs have reported statistically sound data in these patient groups. Most available results concerning pregnancy are obtained from observational studies after birth, assessing outcomes in the newborn or by measuring drug concentrations in the mother and umbilical cord blood. In the case of the lactation period, some studies have evaluated drug concentrations in breastmilk and blood of the mother and/or infant. In this review, exposure to antiretrovirals, immunosuppressants used after solid organ transplantation, and antiepileptics during pregnancy and lactation has been discussed in detail.}, }
@article {pmid32068151, year = {2020}, author = {Hedin, CRH and Sado, G and Ndegwa, N and Lytvyak, E and Mason, A and Montano-Loza, A and Gerussi, A and Saffioti, F and Thorburn, D and Nilsson, E and Larsson, G and Moum, BA and van Munster, KN and Ponsioen, CY and Levy, C and Nogueira, NF and Bowlus, CL and Gotlieb, N and Shibolet, O and Lynch, KD and Chapman, RW and Rupp, C and Vesterhus, M and Jørgensen, KK and Rorsman, F and Schramm, C and Sabino, J and Vermeire, S and Zago, A and Cazzagon, N and Marschall, HU and Ytting, H and Ben Belkacem, K and Chazouilleres, O and Almer, S and ,  and Bergquist, A}, title = {Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {18}, number = {10}, pages = {2295-2304.e2}, doi = {10.1016/j.cgh.2020.02.014}, pmid = {32068151}, issn = {1542-7714}, mesh = {Adalimumab/adverse effects ; *Cholangitis, Sclerosing/drug therapy ; Humans ; *Inflammatory Bowel Diseases/drug therapy ; Infliximab/adverse effects ; Retrospective Studies ; Tumor Necrosis Factor Inhibitors ; Tumor Necrosis Factor-alpha ; }, abstract = {BACKGROUND &amp; AIMS: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD.<br><br>METHODS: We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy.<br><br>RESULTS: Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P&#xa0;= .035). Factors associated with lower ALP were normal ALP at baseline (P < .01), treatment with adalimumab (P&#xa0;= .090), and treatment in Europe (P&#xa0;= .083).<br><br>CONCLUSIONS: In a retrospective analysis of 141 patients with PSC and IBD, anti-TNF agents were moderately effective and were not associated with exacerbation of PSC symptoms or specific side effects. Prospective studies are needed to investigate the association between use of adalimumab and reduced serum levels of ALP further.}, }
@article {pmid32068018, year = {2020}, author = {Liu, X and Liu, Y and Chen, X and Wang, C and Chen, X and Liu, W and Huang, K and Chen, H and Yang, J}, title = {Multi-walled carbon nanotubes exacerbate doxorubicin-induced cardiotoxicity by altering gut microbiota and pulmonary and colonic macrophage phenotype in mice.}, journal = {Toxicology}, volume = {435}, number = {}, pages = {152410}, doi = {10.1016/j.tox.2020.152410}, pmid = {32068018}, issn = {1879-3185}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Antibiotics, Antineoplastic/*toxicity ; Apoptosis/drug effects ; Cells, Cultured ; Chemokine CCL2/blood ; Colon/*drug effects/immunology/metabolism/microbiology ; Doxorubicin/*toxicity ; Dysbiosis ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Heart Diseases/blood/*chemically induced/immunology/microbiology ; Interleukin-1beta/blood ; Lung/*drug effects/immunology/metabolism ; Macrophages/*drug effects/immunology/metabolism ; Male ; Mice, Inbred C57BL ; Myocytes, Cardiac/*drug effects/metabolism/pathology ; Nanotubes, Carbon/*toxicity ; Phenotype ; Tumor Necrosis Factor-alpha/blood ; }, abstract = {Epidemiologic studies show that the levels of air pollutants and particulate matter are positively associated with the morbidity and mortality of cardiovascular diseases. Here we demonstrate that the intratracheal instillation of multi-walled carbon nanotubes (MWCNTs), a standard fine particle, exacerbate doxorubicin (DOX)-induced cardiotoxicity in mice through altering gut microbiota and pulmonary and colonic macrophage phenotype. MWCNTs (25 μg/kg per day, 5 days a week for 3 weeks) promoted cardiotoxicity and apoptosis in the DOX (2 mg/kg, twice a week for 5 weeks)-treated C57BL/6 mice. MWCNTs exaggerated DOX-induced gut microbiota dysbiosis characterized by the increased abundances of Helicobacteraceae and Coriobacteriaceae. In addition, MWCNTs promoted DOX-induced M1-like polarization of colonic macrophages with an increase in TNF-α, IL-1β and CC chemokine ligand 2 in peripheral blood. Importantly, treatment with the antibiotics attenuated MWCNTs plus DOX-induced apoptosis of cardiomyocytes and M1-like polarization of colonic macrophages. The fecal microbiota transplantation demonstrated that MWCNTs exaggerated DOX-induced cardiotoxicity with M1-like polarization of colonic macrophages. The conditioned medium from MWCNTs-treated pulmonary macrophages promoted DOX-induced gut microbiota dysbiosis and colonic macrophage polarization. Furthermore, the co-culture of macrophages and fecal bacteria promoted M1-like macrophage polarization and their production of TNF-α and IL-1β, and thereby exacerbated the effects of MWCNTs. Moreover, IL-1β and TNF-α blockade, either alone or in combination attenuated MWCNTs-exacerbated cardiotoxicity. In summary, MWCNTs exacerbate DOX-induced cardiotoxicity in mice through gut microbiota and pulmonary and colonic macrophage interaction. Our findings identify a novel mechanism of action of inhaled particle-driven cardiotoxicity.}, }
@article {pmid32066789, year = {2020}, author = {van der Eijk, JAJ and Rodenburg, TB and de Vries, H and Kjaer, JB and Smidt, H and Naguib, M and Kemp, B and Lammers, A}, title = {Early-life microbiota transplantation affects behavioural responses, serotonin and immune characteristics in chicken lines divergently selected on feather pecking.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {2750}, pmid = {32066789}, issn = {2045-2322}, mesh = {Aggression/psychology ; Animal Welfare ; Animals ; Antibodies/*blood ; Anxiety/immunology/*microbiology/physiopathology ; Bacteria/classification/immunology ; *Behavior, Animal ; Chickens/blood/genetics/immunology/*microbiology ; Corticosterone/blood ; Feathers ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/*immunology ; Genotype ; Male ; Serotonin/blood ; Time Factors ; }, abstract = {Gut microbiota influences host behaviour and physiology, such as anxiety, stress, serotonergic and immune systems. These behavioural and physiological characteristics are related to feather pecking (FP), a damaging behaviour in chickens that reduces animal welfare and productivity. Moreover, high FP (HFP) and low FP (LFP) lines differed in microbiota composition. However, it is unknown whether microbiota can influence the development of FP. For the first time, we identified the effects of microbiota transplantation on FP, and behavioural and physiological characteristics related to FP. HFP and LFP chicks received sterile saline (control), HFP or LFP microbiota transplantation during the first two weeks post-hatch. Microbiota transplantation influenced behavioural responses of the HFP line during treatment and of the LFP line after treatment. In both lines, homologous microbiota transplantation (i.e., receiving microbiota from their line) resulted in more active behavioural responses. Furthermore, microbiota transplantation influenced immune characteristics (natural antibodies) in both lines and peripheral serotonin in the LFP line. However, limited effects on microbiota composition, stress response (corticosterone) and FP were noted. Thus, early-life microbiota transplantation had immediate and long-term effects on behavioural responses and long-term effects on immune characteristics and peripheral serotonin; however, the effects were dependent on host genotype. Since early-life microbiota transplantation influenced behavioural and physiological characteristics that are related to FP, it could thus influence the development of FP later in life.}, }
@article {pmid32066679, year = {2020}, author = {Xiao, J and Wang, T and Xu, Y and Gu, X and Li, D and Niu, K and Wang, T and Zhao, J and Zhou, R and Wang, HL}, title = {Long-term probiotic intervention mitigates memory dysfunction through a novel H3K27me3-based mechanism in lead-exposed rats.}, journal = {Translational psychiatry}, volume = {10}, number = {1}, pages = {25}, pmid = {32066679}, issn = {2158-3188}, support = {31401671//National Science Foundation of China | Young Scientists Fund/International ; 81773475, 21477031//National Science Foundation of China | Major Research Plan/International ; }, mesh = {Animals ; Epigenesis, Genetic ; Female ; Hippocampus/metabolism ; *Histones/genetics ; Neurons/metabolism ; Pregnancy ; *Probiotics ; Rats ; }, abstract = {Chronic lead exposure is associated with the development of neurodegenerative diseases, characterized by the long-term memory decline. However, whether this pathogenesis could be prevented through adjusting gut microbiota is not yet understood. To address the issue, pregnant rats and their female offspring were treated with lead (125 ppm) or separately the extra probiotics (10[10] organisms/rat/day) till adulthood. For results, memory dysfunction was alleviated by the treatment of multispecies probiotics. Meanwhile, the gut microbiota composition was partially normalized against lead-exposed rats, which in turn mediated the memory repairment via fecal transplantation trials. In the molecular aspect, the decreased H3K27me3 (trimethylation of histone H3 Lys 27) in the adult hippocampus was restored with probiotic intervention, an epigenetic event mediated by EZH2 (enhancer of zeste homolog 2) at early developmental stage. In a neural cellular model, EZH2 overexpression showed the similar rescue effect with probiotics, whereas its blockade led to the neural re-damages. Regarding the gut-brain inflammatory mediators, the disrupted IL-6 (interleukin 6) expression was resumed by probiotic treatment. Intraperitoneal injection of tocilizumab, an IL-6 receptor antagonist, upregulated the hippocampal EZH2 level and consequently alleviated the memory injuries. In conclusion, reshaping gut microbiota could mitigate memory dysfunction caused by chronic lead exposure, wherein the inflammation-hippocampal epigenetic pathway of IL-6-EZH2-H3K27me3, was first proposed to mediate the studied gut-brain communication. These findings provided insight with epigenetic mechanisms underlying a unique gut-brain interaction, shedding light on the safe and non-invasive treatment of neurodegenerative disorders with environmental etiology.}, }
@article {pmid32063856, year = {2019}, author = {Wu, H and Rao, Q and Ma, GC and Yu, XH and Zhang, CE and Ma, ZJ}, title = {Effect of Triptolide on Dextran Sodium Sulfate-Induced Ulcerative Colitis and Gut Microbiota in Mice.}, journal = {Frontiers in pharmacology}, volume = {10}, number = {}, pages = {1652}, pmid = {32063856}, issn = {1663-9812}, abstract = {Triptolide is beneficial for the treatment of ulcerative colitis (UC), which is closely related to the gut microbiota. However, whether the therapeutic effects of triptolide involve the regulation of the gut microbiota is still unclear. In the present study, animal models of UC mice induced by dextran sodium sulfate (DSS) were established, the changes of gut microbiota in mice were detected by high-throughput sequencing. The effects of triptolide on DSS-induced UC mouse and its gut microbiota were studied. As a result, we found that triptolide exerted anti-inflammatory and therapeutic effects on UC mice. Sequencing results for the gut microbiota showed that the composition of the gut microbiota from DSS group was disordered as compared with that from the control group, consistent with a decrease in the abundance of flora. Triptolide treatment accelerated the recovery of the population of the gut microbiota and significantly improved the microbial diversity. At the phylum level, the population of Bacteroidetes decreased and that of Firmicutes increased. At the genus level, Bacteroides and Lachnospiraceae counts decreased. Thus, triptolide could regulate the composition of the gut microbiota, accelerate the recovery of microbiota, and exert good therapeutic effects in UC mice. Our results also revealed that fecal transplantation from triptolide-treated mice could relieve UC. This study provides a reference for the rational use of triptolide for the treatment of UC.}, }
@article {pmid32061326, year = {2020}, author = {Olesen, SW and Panchal, P and Chen, J and Budree, S and Osman, M}, title = {Global disparities in faecal microbiota transplantation research.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {5}, number = {3}, pages = {241}, doi = {10.1016/S2468-1253(19)30452-2}, pmid = {32061326}, issn = {2468-1253}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; Clinical Trials as Topic ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/epidemiology/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods/statistics &amp; numerical data/trends ; Health Services Accessibility/statistics &amp; numerical data ; Healthcare Disparities ; Humans ; Infant ; Infant, Newborn ; Inflammatory Bowel Diseases/epidemiology/microbiology/*therapy ; Registries ; }, }
@article {pmid32061053, year = {2020}, author = {Whitsett, M and Feldman, DM and Jacobson, I}, title = {Hepatitis E Virus Infection in the United States: Current Understanding of the Prevalence and Significance in the Liver Transplant Patient Population and Proposed Diagnostic and Treatment Strategies.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {26}, number = {5}, pages = {709-717}, doi = {10.1002/lt.25732}, pmid = {32061053}, issn = {1527-6473}, mesh = {Animals ; *Hepatitis E/diagnosis/epidemiology/therapy ; *Hepatitis E virus ; Humans ; Liver Cirrhosis ; *Liver Transplantation/adverse effects ; Prevalence ; United States/epidemiology ; }, abstract = {Hepatitis E virus (HEV), of the family Herpesviridae, is a virus that infects nearly 20 million people per year throughout the world. HEV is most commonly transmitted via the fecal-oral route and has long been described as a virus that afflicts only those in resource-poor countries. However, HEV has been detected in numerous animal carriers, various food sources, and even in human blood products in resource-rich regions of the world. HEV is of importance in the transplant patient population because of its ability to cause chronic viral infection in these patients can lead to graft loss and cirrhosis. In this review, we discuss the current knowledge of HEV as it pertains to the liver transplant patient population and discuss diagnosis and treatment of this infection.}, }
@article {pmid32057278, year = {2020}, author = {Cheng, YW and Fischer, M}, title = {Clinical management of severe, fulminant, and refractory Clostridioides difficile infection.}, journal = {Expert review of anti-infective therapy}, volume = {18}, number = {4}, pages = {323-333}, doi = {10.1080/14787210.2020.1730814}, pmid = {32057278}, issn = {1744-8336}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/epidemiology/mortality/*therapy ; Colectomy ; *Fecal Microbiota Transplantation ; Hospitalization ; Humans ; Practice Guidelines as Topic ; Severity of Illness Index ; }, abstract = {Introduction: Up to 15% of hospitalized patients with Clostridioides difficile infection (CDI) develop severe CDI (SCDI) or Fulminant CDI (FCDI). Due to high rates of mortality in medically-refractory CDI cases, 30% of patients with severe infection historically require surgical intervention. However, colectomy itself is an imperfect solution because it is difficult to predict who will fail medical therapy, patients with SCDI are more likely to have underlying medical conditions that make them poor surgical candidates, and post-surgical mortality still approaches 30-50%.Areas covered: This review will serve as a clinically-based review of severe and fulminant CDI management including discussion of models to predict severe infection, emerging treatments, novel targets for therapy, and innovations in surgical management.Expert opinion: Among the most promising studies to emerge in the last decade have involved fecal microbiota transplantation (FMT), which is already recommended by multiple society guidelines for recurrent CDI (RCDI). In the case of SCDI/FCDI, multiple studies have safely and successfully utilized FMT to produce rates of cure in the 70-90% range. Additionally, patients who have FCDI refractory to medical therapy and are poor candidates for colectomy may benefit from FMT as salvage therapy.}, }
@article {pmid32057270, year = {2020}, author = {Hollanda Martins Da Rocha, M and Lee, ADW and Marin, MLM and Faintuch, S and Mishaly, A and Faintuch, J}, title = {Treating short bowel syndrome with pharmacotherapy.}, journal = {Expert opinion on pharmacotherapy}, volume = {21}, number = {6}, pages = {709-720}, doi = {10.1080/14656566.2020.1724959}, pmid = {32057270}, issn = {1744-7666}, mesh = {Adult ; Animals ; Antidiarrheals/*therapeutic use ; Glucagon-Like Peptide 2/*therapeutic use ; Humans ; Intestines/*physiopathology ; Off-Label Use ; Parenteral Nutrition, Home/*methods ; Short Bowel Syndrome/drug therapy/surgery/*therapy ; }, abstract = {INTRODUCTION: Short bowel syndrome (SBS) has traditionally been regarded as a rapidly fatal medical catastrophe. The advent of pharmacological options directly targeting disease pathophysiology justified this review.<br><br>AREAS COVERED: Since the 1970s, home parenteral nutrition has reduced mortality, converting SBS into a chronic and disabling compensated and occasionally curable illness. Off-label antidiarrheal drugs and related products, though having minimal scientific evidence of efficacy, represent the standard-of-care and are here reviewed. Trophic intestinal hormones, including GLP-2 and its analogs, have great promise for alleviating malabsorption, the most important symptom within a nonsurgical, routine outpatient framework. Current indications involve adults with massive intestinal losses (fecal wet weight >1500 g/day). Surgical options such as intestinal lengthening or transplantation are also addressed although these options are considerably more aggressive and have stricter indications.<br><br>EXPERT OPINION: GLP-2 analogs are the first candidates from a pioneering pharmacotherapic family within the SBS framework, namely disease-modifying, absorption-restoring agents. This family of drugs, potentially applicable in all contexts of severe intestinal loss, could become the therapeutic benchmark of the near future.}, }
@article {pmid32056091, year = {2020}, author = {Saurman, V and Margolis, KG and Luna, RA}, title = {Autism Spectrum Disorder as a Brain-Gut-Microbiome Axis Disorder.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {818-828}, pmid = {32056091}, issn = {1573-2568}, support = {R01 DK126644/DK/NIDDK NIH HHS/United States ; R01 NS015547/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Autism Spectrum Disorder/*microbiology/psychology/therapy ; Brain/*microbiology/physiology ; Fecal Microbiota Transplantation/trends ; Gastrointestinal Diseases/*microbiology/psychology/therapy ; *Gastrointestinal Microbiome/physiology ; Gastrointestinal Tract/*microbiology/physiology ; Humans ; Probiotics/administration &amp; dosage ; }, abstract = {While there are numerous medical comorbidities associated with ASD, gastrointestinal (GI) issues have a significant impact on quality of life for these individuals. Recent findings continue to support the relationship between the gut microbiome and both GI symptoms and behavior, but the heterogeneity within the autism spectrum requires in-depth clinical characterization of these clinical cohorts. Large, diverse, well-controlled studies in this area of research are still needed. Although there is still much to discover about the brain-gut-microbiome axis in ASD, microbially mediated therapies, specifically probiotics and fecal microbiota transplantation have shown promise in the treatment of GI symptoms in ASD, with potential benefit to the core behavioral symptoms of ASD as well. Future research and clinical trials must increasingly consider complex phenotypes in ASD in stratification of large datasets as well as in design of inclusion criteria for individual therapeutic interventions.}, }
@article {pmid32055962, year = {2020}, author = {Shin, JH and Lee, YK and Shon, WJ and Kim, B and Jeon, CO and Cho, JY and Morse, HC and Choi, EY and Shin, DM}, title = {Gut microorganisms and their metabolites modulate the severity of acute colitis in a tryptophan metabolism-dependent manner.}, journal = {European journal of nutrition}, volume = {59}, number = {8}, pages = {3591-3601}, doi = {10.1007/s00394-020-02194-4}, pmid = {32055962}, issn = {1436-6215}, support = {HI16C0047//Ministry of Health and Welfare/ ; }, mesh = {Animals ; *Colitis/chemically induced ; Dextran Sulfate ; Disease Models, Animal ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Tryptophan ; }, abstract = {PURPOSE: Growing evidence shows that nutrient metabolism affects inflammatory bowel diseases (IBD) development. Previously, we showed that deficiency of indoleamine 2,3-dioxygenase 1 (Ido1), a tryptophan-catabolizing enzyme, reduced the severity of dextran sulfate sodium (DSS)-induced colitis in mice. However, the roles played by intestinal microbiota in generating the differences in disease progression between Ido1[+/+] and Ido1[-/-] mice are unknown. Therefore, we aimed to investigate the interactions between the intestinal microbiome and host IDO1 in governing intestinal inflammatory responses.<br><br>METHODS: Microbial 16s rRNA sequencing was conducted in Ido1[+/+] and Ido1[-/-] mice after DSS treatment. Bacteria-derived tryptophan metabolites were measured in urine. Transcriptome analysis revealed the effects of the metabolite and IDO1 expression in HCT116 cells. Colitis severity of Ido1[+/+] was compared to Ido1[-/-] mice following fecal microbiota transplantation (FMT).<br><br>RESULTS: Microbiome analysis through 16S-rRNA gene sequencing showed that IDO1 deficiency increased intestinal bacteria that use tryptophan preferentially to produce indolic compounds. Urinary excretion of 3-indoxyl sulfate, a metabolized form of gut bacteria-derived indole, was significantly higher in Ido1[-/-] than in Ido1[+/+] mice. Transcriptome analysis showed that tight junction transcripts were significantly increased by indole treatment in HCT116 cells; however, the effects were diminished by IDO1 overexpression. Using FMT experiments, we demonstrated that bacteria from Ido1[-/-] mice could directly attenuate the severity of DSS-induced colitis.<br><br>CONCLUSIONS: Our results provide evidence that a genetic defect in utilizing tryptophan affects intestinal microbiota profiles, altering microbial metabolites, and colitis development. This suggests that the host and intestinal microbiota communicate through shared nutrient metabolic networks.}, }
@article {pmid32053787, year = {2020}, author = {Carlson, PE}, title = {Regulatory Considerations for Fecal Microbiota Transplantation Products.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {2}, pages = {173-175}, doi = {10.1016/j.chom.2020.01.018}, pmid = {32053787}, issn = {1934-6069}, mesh = {Clostridioides difficile ; Clostridium Infections/prevention &amp; control ; *Fecal Microbiota Transplantation/methods/trends ; Feces/*microbiology ; Gastrointestinal Microbiome ; Living Donors ; Safety ; Social Control, Formal ; Treatment Outcome ; }, abstract = {Fecal microbiota for transplantation (FMT) is being studied as a potential intervention for numerous conditions. The regulation of FMT by the FDA is discussed along with FMT donor screening and manufacturing considerations. The FDA is committed to ensuring that FMT products can be safely tested in clinical trials.}, }
@article {pmid32053786, year = {2020}, author = {Markey, KA and van den Brink, MRM and Peled, JU}, title = {Therapeutics Targeting the Gut Microbiome: Rigorous Pipelines for Drug Development.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {2}, pages = {169-172}, doi = {10.1016/j.chom.2020.01.022}, pmid = {32053786}, issn = {1934-6069}, support = {P01 AG052359/AG/NIA NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; }, mesh = {Drug Development ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; }, abstract = {Restoration of the gut microbiome is a promising preventive and therapeutic strategy in a number of clinical scenarios. We discuss here the scientific and clinical challenges of engineering and implementing these strategies.}, }
@article {pmid32047670, year = {2020}, author = {Meighani, A and Alimirah, M and Ramesh, M and Salgia, R}, title = {Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease.}, journal = {International journal of hepatology}, volume = {2020}, number = {}, pages = {1874570}, pmid = {32047670}, issn = {2090-3448}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a well-established therapeutic option for patients with antibiotic resistant Clostridioides difficile infection (CDI). However, the efficacy of FMT in patients with chronic liver disease remains elusive.<br><br>AIMS: We studied the effect of FMT on chronic liver disease (CLD) patients with CDI at our tertiary medical center.<br><br>METHODS: A cohort of all patients who received FMT from December 2012 to May 2014 for refractory or recurrent CDI was identified. Patients were monitored for a year after FMT. Descriptive analysis was conducted to compare the effect of FMT in patients with and without CLD.<br><br>RESULTS: A total of 201 patients with CDI received FMT, 14 of which had a history of CLD. Nine of these patients exhibited cirrhosis of the liver with a mean Child-Turcotte-Pugh score of 8. CDI development in these patients was associated with recent exposure to antibiotics and was observed to be significantly different between both groups (17% of CLD patients vs. 58% in the general cohort, p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%), p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%).<br><br>CONCLUSION: FMT is a safe and effective therapy against CDI for patients with CLD and cirrhosis.}, }
@article {pmid32047611, year = {2020}, author = {Quigley, EMM and Gajula, P}, title = {Recent advances in modulating the microbiome.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {}, pmid = {32047611}, issn = {2046-1402}, mesh = {Animals ; Anti-Bacterial Agents ; Diet ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; Probiotics ; }, abstract = {We are in the midst of "the microbiome revolution"-not a day goes by without some new revelation on the potential role of the gut microbiome in some disease or disorder. From an ever-increasing recognition of the many roles of the gut microbiome in health and disease comes the expectation that its modulation could treat or prevent these very same diseases. A variety of interventions could, at least in theory, be employed to alter the composition or functional capacity of the microbiome, ranging from diet to fecal microbiota transplantation (FMT). For some, such as antibiotics, prebiotics, and probiotics, an extensive, albeit far from consistent, literature already exists; for others, such as other dietary supplements and FMT, high-quality clinical studies are still relatively few in number. Not surprisingly, researchers have turned to the microbiome itself as a source for new entities that could be used therapeutically to manipulate the microbiome; for example, some probiotic strains currently in use were sourced from the gastrointestinal tract of healthy humans. From all of the extant studies of interventions targeted at the gut microbiome, a number of important themes have emerged. First, with relatively few exceptions, we are still a long way from a precise definition of the role of the gut microbiome in many of the diseases where a disturbed microbiome has been described-association does not prove causation. Second, while animal models can provide fascinating insights into microbiota-host interactions, they rarely recapitulate the complete human phenotype. Third, studies of several interventions have been difficult to interpret because of variations in study population, test product, and outcome measures, not to mention limitations in study design. The goal of microbiome modulation is a laudable one, but we need to define our targets, refine our interventions, and agree on outcomes.}, }
@article {pmid32047093, year = {2020}, author = {Haifer, C and Kelly, CR and Paramsothy, S and Andresen, D and Papanicolas, LE and McKew, GL and Borody, TJ and Kamm, M and Costello, SP and Andrews, JM and Begun, J and Chan, HT and Connor, S and Ghaly, S and Johnson, PD and Lemberg, DA and Paramsothy, R and Redmond, A and Sheorey, H and van der Poorten, D and Leong, RW}, title = {Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice.}, journal = {Gut}, volume = {69}, number = {5}, pages = {801-810}, doi = {10.1136/gutjnl-2019-320260}, pmid = {32047093}, issn = {1468-3288}, mesh = {Australia ; Clostridium Infections/*therapy ; Consensus ; Donor Selection ; Fecal Microbiota Transplantation/*methods ; Female ; Health Facilities/statistics &amp; numerical data ; Humans ; Male ; *Practice Guidelines as Topic ; Treatment Outcome ; }, abstract = {OBJECTIVE: Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent Clostridioides difficile infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications.<br><br>DESIGN: For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.<br><br>RESULTS: Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development.<br><br>CONCLUSIONS: These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.}, }
@article {pmid32044317, year = {2020}, author = {Aron-Wisnewsky, J and Warmbrunn, MV and Nieuwdorp, M and Clément, K}, title = {Nonalcoholic Fatty Liver Disease: Modulating Gut Microbiota to Improve Severity?.}, journal = {Gastroenterology}, volume = {158}, number = {7}, pages = {1881-1898}, doi = {10.1053/j.gastro.2020.01.049}, pmid = {32044317}, issn = {1528-0012}, mesh = {Animals ; Diet, Healthy ; *Dietary Supplements/adverse effects ; Dysbiosis ; Exercise ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; *Healthy Lifestyle ; Humans ; Intestines/*microbiology ; Liver/*metabolism/pathology ; Non-alcoholic Fatty Liver Disease/diagnosis/metabolism/microbiology/*therapy ; Risk Reduction Behavior ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {Gut microbiota plays a role in the pathophysiology of metabolic diseases, which include nonalcoholic fatty liver diseases, through the gut-liver axis. To date, clinical guidelines recommend a weight loss goal of 7%-10% to improve features of nonalcoholic fatty liver diseases. Because this target is not easily achieved by all patients, alternative therapeutic options are currently being evaluated. This review focuses on therapeutics that aim to modulate the gut microbiota and the gut-liver axis. We discuss how probiotics, prebiotics, synbiotic, fecal microbiota transfer, polyphenols, specific diets, and exercise interventions have been found to modify gut microbiota signatures; improve nonalcoholic fatty liver disease outcomes; and detail, when available, the different mechanisms by which these beneficial outcomes might occur. Apart from probiotics that have already been tested in human randomized controlled trials, most of these potential therapeutics have been studied in animals. Their efficacy still warrants confirmation in humans using appropriate design.}, }
@article {pmid32044171, year = {2020}, author = {Ding, X and Li, Q and Li, P and Chen, X and Xiang, L and Bi, L and Zhu, J and Huang, X and Cui, B and Zhang, F}, title = {Fecal microbiota transplantation: A promising treatment for radiation enteritis?.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {143}, number = {}, pages = {12-18}, doi = {10.1016/j.radonc.2020.01.011}, pmid = {32044171}, issn = {1879-0887}, mesh = {Aged ; Aged, 80 and over ; *Enteritis/etiology/therapy ; *Fecal Microbiota Transplantation ; Feces ; Female ; Humans ; Middle Aged ; Pilot Projects ; RNA, Ribosomal, 16S ; Treatment Outcome ; }, abstract = {BACKGROUND: Increasing evidence has indicated that gut microbiota is closely associated with radiation-induced bowel injury. We aimed to evaluate the safety and efficacy of fecal microbiota transplantation (FMT) in patients with chronic radiation enteritis (CRE).<br><br>METHODS: A pilot study of FMT for CRE was performed. The primary outcomes were safety and response to FMT which was defined as a &#x2265;1-grade reduction in Radiation Therapy Oncology Group (RTOG/EORTC) late toxicity grade from baseline, by 8&#xa0;weeks post-FMT. The secondary outcomes included a decrease in the severity of four common symptoms (diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence) in CRE and changes in Karnofsky Performance Status (KPS) score. Microbial analyses were performed by 16S rRNA sequencing.<br><br>RESULTS: Five female patients underwent FMT from January to November 2018 with a median age of 58 (range 45-81) years. The median baseline RTOG/EORTC grade was 2 (range 2-4). Three patients responded to FMT and experienced improvement in diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence as well as a decrease in KPS score. No FMT-related death and infectious complications occurred. One mild FMT-related AE was observed during a follow-up ranged from 8 to 18&#xa0;months. 16S rRNA sequencing indicated that FMT altered the composition of gut microbiota of patients.<br><br>CONCLUSION: The present case series first demonstrated that FMT might be safe and effective to improve intestinal symptoms and mucosal injury in patients with CRE for a period of time. Trial registration ID: NCT03516461.}, }
@article {pmid32043638, year = {2020}, author = {Han, J and Wang, X and Tang, S and Lu, C and Wan, H and Zhou, J and Li, Y and Ming, T and Wang, ZJ and Su, X}, title = {Protective effects of tuna meat oligopeptides (TMOP) supplementation on hyperuricemia and associated renal inflammation mediated by gut microbiota.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {34}, number = {4}, pages = {5061-5076}, doi = {10.1096/fj.201902597RR}, pmid = {32043638}, issn = {1530-6860}, mesh = {Animals ; Anti-Inflammatory Agents/administration &amp; dosage/chemistry/*therapeutic use ; Dietary Supplements ; Fish Proteins, Dietary/administration &amp; dosage/chemistry/*therapeutic use ; *Gastrointestinal Microbiome ; Hyperuricemia/*drug therapy/microbiology ; Intestinal Mucosa/metabolism ; Kidney/metabolism ; Male ; Mice ; Mice, Inbred ICR ; Myeloid Differentiation Factor 88/metabolism ; NF-kappa B/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Nephritis/*drug therapy/microbiology ; Oligopeptides/administration &amp; dosage/chemistry/*therapeutic use ; Toll-Like Receptor 4/metabolism ; Tuna ; Uric Acid/metabolism ; }, abstract = {Recently, interest in using whole food-derived mixtures to alleviate chronic metabolic syndrome through potential synergistic interactions among different components is increasing. In this study, the effects and mechanisms of tuna meat oligopeptides (TMOP) on hyperuricemia and associated renal inflammation were investigated in mice. Dietary administration of TMOP alleviated hyperuricemia and renal inflammation phenotypes, reprogramed uric acid metabolism pathways, inhibited the activation of NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathways, and suppressed the phosphorylation of p65-NF-κB. In addition, TMOP treatments repaired the intestinal epithelial barrier, reversed the gut microbiota dysbiosis and increased the production of short-chain fatty acids. Moreover, the antihyperuricemia effects of TMOP were transmissible by transplanting the fecal microbiota from TMOP-treated mice, indicating that the protective effects were at least partially mediated by the gut microbiota. Thus, for the first time, we clarify the potential effects of TMOP as a whole food derived ingredient on alleviating hyperuricemia and renal inflammation in mice, and additional efforts are needed to confirm the beneficial effects of TMOP on humans.}, }
@article {pmid32042169, year = {2020}, author = {Moss, EL and Maghini, DG and Bhatt, AS}, title = {Complete, closed bacterial genomes from microbiomes using nanopore sequencing.}, journal = {Nature biotechnology}, volume = {38}, number = {6}, pages = {701-707}, pmid = {32042169}, issn = {1546-1696}, support = {R01 AI148623/AI/NIAID NIH HHS/United States ; P30 AG066515/AG/NIA NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; P50 AG047366/AG/NIA NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Animals ; DNA, Bacterial/analysis/genetics ; Dogs ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Genome, Bacterial/*genetics ; Humans ; Metagenomics/*methods ; Mice ; Nanopore Sequencing/*methods ; Sequence Analysis, DNA/*methods ; }, abstract = {Microbial genomes can be assembled from short-read sequencing data, but the assembly contiguity of these metagenome-assembled genomes is constrained by repeat elements. Correct assignment of genomic positions of repeats is crucial for understanding the effect of genome structure on genome function. We applied nanopore sequencing and our workflow, named Lathe, which incorporates long-read assembly and short-read error correction, to assemble closed bacterial genomes from complex microbiomes. We validated our approach with a synthetic mixture of 12 bacterial species. Seven genomes were completely assembled into single contigs and three genomes were assembled into four or fewer contigs. Next, we used our methods to analyze metagenomics data from 13 human stool samples. We assembled 20 circular genomes, including genomes of Prevotella copri and a candidate Cibiobacter sp. Despite the decreased nucleotide accuracy compared with alternative sequencing and assembly approaches, our methods improved assembly contiguity, allowing for investigation of the role of repeat elements in microbial function and adaptation.}, }
@article {pmid32041784, year = {2020}, author = {Konuma, T and Kohara, C and Watanabe, E and Takahashi, S and Ozawa, G and Suzuki, K and Mizukami, M and Nagai, E and Jimbo, K and Kaito, Y and Isobe, M and Kato, S and Takahashi, S and Chiba, A and Miyake, S and Tojo, A}, title = {Reconstitution of Circulating Mucosal-Associated Invariant T Cells after Allogeneic Hematopoietic Cell Transplantation: Its Association with the Riboflavin Synthetic Pathway of Gut Microbiota in Cord Blood Transplant Recipients.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {204}, number = {6}, pages = {1462-1473}, doi = {10.4049/jimmunol.1900681}, pmid = {32041784}, issn = {1550-6606}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria/genetics/isolation &amp; purification/metabolism ; Biosynthetic Pathways/immunology ; Cord Blood Stem Cell Transplantation/*adverse effects ; Cross-Sectional Studies ; DNA, Bacterial/isolation &amp; purification ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Graft vs Host Disease/blood/*immunology ; Healthy Volunteers ; Hematologic Diseases/therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Host Microbial Interactions/immunology ; Humans ; Male ; Middle Aged ; Mucosal-Associated Invariant T Cells/*immunology ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Retrospective Studies ; Riboflavin/biosynthesis ; Transplantation, Homologous/adverse effects ; Young Adult ; }, abstract = {Mucosal-associated invariant T (MAIT) cells are a type of innate lymphocyte and recognize riboflavin (vitamin B2) synthesis products presented by MHC-related protein 1. We investigated long-term reconstitution of MAIT cells and its association with chronic graft-versus-host disease (cGVHD) in a cross-sectional cohort of 173 adult patients after allogeneic hematopoietic cell transplantation. According to donor source, the number of MAIT cells significantly correlated with time after cord blood transplantation (CBT) but not with time after bone marrow transplantation or peripheral blood stem cell transplantation. The number of MAIT cells was significantly lower in patients with cGVHD compared with patients without cGVHD. We also examined the association between MAIT cell reconstitution and gut microbiota as evaluated by 16S ribosomal sequencing of stool samples 1 mo post-CBT in 27 adult patients undergoing CBT. The diversity of gut microbiota was positively correlated with better MAIT cell reconstitution after CBT. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis indicated that amounts of ribB and ribA genes were significantly higher in the microbiomes of patients with subsequent MAIT cell reconstitution after CBT. In conclusion, long-term MAIT cell reconstitution is dependent on the type of donor source. Our data also unveiled an important role for the interaction of circulating MAIT cells with gut microbiota in humans.}, }
@article {pmid32040664, year = {2020}, author = {Abu-Sbeih, H and Wang, Y}, title = {Gut Microbiome and Immune Checkpoint Inhibitor-Induced Enterocolitis.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {797-799}, pmid = {32040664}, issn = {1573-2568}, mesh = {Animals ; Antineoplastic Agents, Immunological/*adverse effects/*immunology ; Enterocolitis/*chemically induced/*immunology/microbiology ; Gastrointestinal Microbiome/*drug effects/*immunology ; Humans ; }, abstract = {The gut microbiome is increasingly being described as one of the underlying mechanisms for development of immune checkpoint inhibitor (ICI)-induced colitis. Similarities in gut microbiome profiles have been found among various diseases associated with intestinal inflammation, including inflammatory bowel disease. Certain bacterial species have been reported to be preventive for colitis, as well as beneficial for cancer outcome, in patients receiving ICI therapy. Alternatively, other bacterial classes have been shown to be associated with immunologic alterations causing intestinal inflammation with subsequent increase in the risk of ICI-related colitis. Gut microbiome manipulation by fecal transplantation has been proposed as one of the modalities to ameliorate inflammation in patients with ICI-related colitis refractory to immunosuppressive therapy. Additional investigations are needed to clarify the role of gut microbiome in the pathogenesis of ICI-related colitis.}, }
@article {pmid32040250, year = {2020}, author = {Guo, XY and Liu, XJ and Hao, JY}, title = {Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment.}, journal = {Journal of digestive diseases}, volume = {21}, number = {3}, pages = {147-159}, doi = {10.1111/1751-2980.12849}, pmid = {32040250}, issn = {1751-2980}, support = {81300294//Youth Program of National Natural Science Foundation of China/ ; XXT11//Project of Digestive Medical Coordinated Development Center of Beijing Hospitals Authority/ ; PX2018011//Incubation Program Project of Beijing Municipal Administration of Hospitals of China/ ; 7192072//Beijing Natural Science Foundation/ ; }, mesh = {Colitis, Ulcerative/immunology/microbiology/*therapy ; Dysbiosis/immunology/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunity, Innate ; Intestinal Mucosa/immunology/*microbiology ; Treatment Outcome ; }, abstract = {Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem-based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic-associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.}, }
@article {pmid32039372, year = {2019}, author = {Schwenger, KJ and Clermont-Dejean, N and Allard, JP}, title = {The role of the gut microbiome in chronic liver disease: the clinical evidence revised.}, journal = {JHEP reports : innovation in hepatology}, volume = {1}, number = {3}, pages = {214-226}, pmid = {32039372}, issn = {2589-5559}, abstract = {Recent research has suggested a role for the intestinal microbiota in the pathogenesis and potential treatment of a wide range of liver diseases. The intestinal microbiota and bacterial products may contribute to the development of liver diseases through multiple mechanisms including increased intestinal permeability, chronic systemic inflammation, production of short-chain fatty acids and changes in metabolism. This suggests a potential role for pre-, pro- and synbiotic products in the prevention or treatment of some liver diseases. In addition, there is emerging evidence on the effects of faecal microbial transplant. Herein, we discuss the relationship between the intestinal microbiota and liver diseases, as well as reviewing intestinal microbiota-based treatment options that are currently being investigated.}, }
@article {pmid32036124, year = {2020}, author = {Wang, Y and Xu, L and Sun, X and Wan, X and Sun, G and Jiang, R and Li, W and Tian, Y and Liu, X and Kang, X}, title = {Characteristics of the fecal microbiota of high- and low-yield hens and effects of fecal microbiota transplantation on egg production performance.}, journal = {Research in veterinary science}, volume = {129}, number = {}, pages = {164-173}, doi = {10.1016/j.rvsc.2020.01.020}, pmid = {32036124}, issn = {1532-2661}, mesh = {Animal Feed/analysis ; Animals ; Chickens/*microbiology/physiology ; Fecal Microbiota Transplantation/*veterinary ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; *Oviposition ; }, abstract = {The microbiota that resides in the digestive tract plays pivotal role in maintaining intestinal environmental stability by promoting nutrition digestion and intestinal mucosal immunity. However, whether the intestinal microbiota in laying hens affects egg laying- performance is not known. In this study, 16S rDNA gene sequencing and fecal microbiota transplantation were used to determine the structure of the intestinal microbiota and the effect of the intestinal microbiota on egg production. The results revealed that Firmicutes were dominant in both the H (high egg laying rates) and L (low egg laying rates) groups, while Bacteroides, Actinobacteria and Proteobacteria were significantly enriched in the L group compared to the H group. The laying rates were weakly affected in H hens transplanted with the fecal microbiota from L hens, except for temporary fluctuation, while the egg laying rates were significantly increased in L hens transplanted with the fecal microbiota from H hens. Therefore, we concluded that the population structure of the intestinal microbiota varied between the H and L groups, and the intestinal microbiota of high-yield laying hens had significant effects on low-yield laying hens performance.}, }
@article {pmid32035985, year = {2020}, author = {Park, HK and Choi, Y and Lee, DH and Kim, S and Lee, JM and Choi, SW and Lee, HR and Rho, M and Park, HS}, title = {Altered gut microbiota by azithromycin attenuates airway inflammation in allergic asthma.}, journal = {The Journal of allergy and clinical immunology}, volume = {145}, number = {5}, pages = {1466-1469.e8}, doi = {10.1016/j.jaci.2020.01.044}, pmid = {32035985}, issn = {1097-6825}, mesh = {Allergens/immunology ; Animals ; Anti-Bacterial Agents/*pharmacology ; Asthma/immunology/*microbiology/therapy ; Azithromycin/*pharmacology ; Bronchoalveolar Lavage Fluid/cytology/immunology/microbiology ; Cefixime/*pharmacology ; Cytokines/immunology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Mice, Inbred BALB C ; Ovalbumin/immunology ; Th2 Cells/drug effects/immunology ; }, }
@article {pmid32034968, year = {2020}, author = {Gryp, T and Glorieux, G and Joossens, M and Vaneechoutte, M}, title = {Comparison of five assays for DNA extraction from bacterial cells in human faecal samples.}, journal = {Journal of applied microbiology}, volume = {129}, number = {2}, pages = {378-388}, pmid = {32034968}, issn = {1365-2672}, support = {G017815N//Fonds Wetenschappelijk Onderzoek/ ; }, mesh = {Bacteria/*genetics/isolation &amp; purification ; DNA, Bacterial/genetics/*isolation &amp; purification ; Feces/*microbiology ; Gastrointestinal Microbiome/genetics ; Humans ; Reagent Kits, Diagnostic ; Real-Time Polymerase Chain Reaction ; }, abstract = {AIM: To determine the most effective DNA extraction method for bacteria in faecal samples.<br><br>MATERIALS AND RESULTS: This study assessed five commercial methods, that is, NucliSens easyMag, QIAamp DNA Stool Mini kit, PureLink Microbiome DNA purification kit, QIAamp PowerFecal DNA kit and RNeasy PowerMicrobiome kit, of which the latter has been optimized for DNA extraction. The DNA quantity and quality were determined using Nanodrop, Qubit and qPCR. The PowerMicrobiome kit recovered the highest DNA concentration, whereby this kit also recovered the highest gene copy number of Gram positives, Gram negatives and total bacteria. Furthermore, the PowerMicrobiome kit in combination with mechanical pre-treatment (bead beating) and with combined enzymatic and mechanical pre-treatment (proteinase K+mutanolysin+bead beating) was more effective than without pre-treatment.<br><br>CONCLUSION: From the five DNA extraction methods that were compared, the PowerMicrobiome kit, preceded by bead beating, which is standard included, was found to be the most effective DNA extraction method for bacteria in faecal samples.<br><br>The quantity and quality of DNA extracted from human faecal samples is a first important step to optimize molecular methods. Here we have shown that the PowerMicrobiome kit is an effective DNA extraction method for bacterial cells in faecal samples for downstream qPCR purpose.}, }
@article {pmid32032696, year = {2020}, author = {Shen, H and Guan, Q and Zhang, X and Yuan, C and Tan, Z and Zhai, L and Hao, Y and Gu, Y and Han, C}, title = {New mechanism of neuroinflammation in Alzheimer's disease: The activation of NLRP3 inflammasome mediated by gut microbiota.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {100}, number = {}, pages = {109884}, doi = {10.1016/j.pnpbp.2020.109884}, pmid = {32032696}, issn = {1878-4216}, mesh = {Alzheimer Disease/*metabolism/pathology ; Animals ; Biomarkers/metabolism ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Hippocampus/metabolism ; Humans ; Inflammation Mediators/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism ; }, abstract = {Alzheimer's disease (AD) is a central degenerative disease characterized by cognitive impairment. Polymerization of β-amyloid has been reported to cause the entanglement of nerve cells, leading to the progressive loss of nerve cells. Accumulative studies have confirmed the important roles of neuroinflammation in the development of AD. In this study, the gut microbiota from AD patients were transplanted into APP/PS1 double transgenic mice. As a result, the expression of NLRP3 was increased in the intestinal tract of mice, and the expression levels of inflammatory factors in peripheral blood were also increased. Consistently, the cognitive impairment was more severe in mice receiving gut microbiota from AD patients than those did not, with activation of microglia in the central hippocampus of mice, and increased expression of neuroinflammatory factors. In APP/PS1 mice transplanted with gut microbiota from AD patients, transplantation of healthy human gut microbiota or oral administration of minocycline was further used to improve the composition of gut microbiota. Consequently, the intestinal expression of NLRP3 was down-regulated, the cognitive ability of mice was improved, the activation of microglia in central hippocampus was suppressed and the expression of neuroinflammatory factors was also down-regulated. After transplantation of gut microbiota from AD patients in C57BL/6 mice, the intestinal expression of NLRP3 was up-regulated. Although the cognitive ability of mice was not significantly changed, the microglia in the hippocampus of mice were still activated and the expression of inflammatory factors was up-regulated. In this study, we found that gut microbiota in AD patients could induce the activation of NLRP3 inflammasome in the intestinal tract of mice, subsequently causing the release of inflammatory factors. The absorption and circulation of inflammatory factors through the intestinal tract could further aggravate the inflammation in the nervous tissues and the activation of microglia. Therefore, improving the composition of gut microbiota in AD patients can further attenuate neuroinflammation, which is considered as a novel idea for AD treatment.}, }
@article {pmid32031511, year = {2020}, author = {Stallmach, A and Steube, A and Grunert, P and Hartmann, M and Biehl, LM and Vehreschild, MJGT}, title = {Fecal Microbiota Transfer.}, journal = {Deutsches Arzteblatt international}, volume = {117}, number = {3}, pages = {31-38}, pmid = {32031511}, issn = {1866-0452}, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Germany ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transfer (FMT) is increasingly being used in Ger- many, as in other countries, for the treatment of recurrent Clostridioides difficile infection (rCDI). FMT is now being performed both for research and in individual patients outside of clinical trials. No compulsory standards have been established to date for donor screening or for the method of fecal transfer. Given the potential dangers of FMT, this would seem to be urgently necessary.<br><br>METHODS: This review is based on pertinent literature retrieved by a selective search, including the reports of consensus conferences from Germany and abroad.<br><br>RESULTS: Because of its high efficacy, FMT is the treatment of choice for rCDI. It is largely free of adverse side effects, even in immune-deficient patients, as long as comprehensive and repeated donor screening has been carried out, with extensive clinical and microbiological testing and with the use of structured questionnaires. The ingestion of frozen, encapsulated microbiota is just as effective as other modes of delivery for the treatment of rCDI.<br><br>CONCLUSION: Encapsulation of the fecal microbiome (FM) and storage at -20&#xb0;C is the method of choice, because it can be standardized with the necessary quality controls and it is readily available. Patients with rCDI should undergo FMT by orally ingesting the capsules. There are ongoing research efforts to identify the active e FM. It is not yet clear when the ultimate goal of recombinant production can be achieved.}, }
@article {pmid32029559, year = {2020}, author = {DeMaere, MZ and Liu, MYZ and Lin, E and Djordjevic, SP and Charles, IG and Worden, P and Burke, CM and Monahan, LG and Gardiner, M and Borody, TJ and Darling, AE}, title = {Metagenomic Hi-C of a Healthy Human Fecal Microbiome Transplant Donor.}, journal = {Microbiology resource announcements}, volume = {9}, number = {6}, pages = {}, pmid = {32029559}, issn = {2576-098X}, abstract = {We report the availability of a high-quality metagenomic Hi-C data set generated from a fecal sample taken from a healthy fecal microbiome transplant donor subject. We report on basic features of the data to evaluate their quality.}, }
@article {pmid32024322, year = {2020}, author = {Park, S and Kang, Y and Koh, H and Kim, S}, title = {Increasing incidence of inflammatory bowel disease in children and adolescents: significance of environmental factors.}, journal = {Clinical and experimental pediatrics}, volume = {63}, number = {9}, pages = {337-344}, pmid = {32024322}, issn = {2713-4148}, abstract = {Inflammatory bowel disease (IBD) is a chronic relapsing immune-mediated disease of the intestinal tract. Although its prevalence is reportedly lower in Asia than in Western countries, the rapid increase in the incidence of IBD has drawn attention to its etiology, including genetic susceptibility and environmental factors. Specifically, recent studies concerning dietary treatments and intestinal microbiota suggest that these factors may interact with the immune system, and the imbalance of this relationship may lead to immune dysregulation in IBD. Changes in diet or alterations in the composition of the intestinal microbiota may be associated with the increasing incidence of IBD in Asia. Here, we aim to review recent studies on the role of diet and intestinal microbiota in IBD pathogenesis and the results of the investigations performed to modulate these factors.}, }
@article {pmid32024079, year = {2020}, author = {Swarte, JC and Douwes, RM and Hu, S and Vich Vila, A and Eisenga, MF and van Londen, M and Gomes-Neto, AW and Weersma, RK and Harmsen, HJM and Bakker, SJL}, title = {Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients.}, journal = {Journal of clinical medicine}, volume = {9}, number = {2}, pages = {}, pmid = {32024079}, issn = {2077-0383}, abstract = {Renal transplantation is life-changing in many aspects. This includes changes to the gut microbiome likely due to exposure to immunosuppressive drugs and antibiotics. As a consequence, renal transplant recipients (RTRs) might suffer from intestinal dysbiosis. We aimed to investigate the gut microbiome of RTRs and compare it with healthy controls and to identify determinants of the gut microbiome of RTRs. Therefore, RTRs and healthy controls participating in the TransplantLines Biobank and Cohort Study (NCT03272841) were included. We analyzed the gut microbiome using 16S rRNA sequencing and compared the composition of the gut microbiome of RTRs to healthy controls using multivariate association with linear models (MaAsLin). Fecal samples of 139 RTRs (50% male, mean age: 58.3 ± 12.8 years) and 105 healthy controls (57% male, mean age: 59.2 ± 10.6 years) were collected. Median time after transplantation of RTRs was 6.0 (1.5-12.5)years. The microbiome composition of RTRs was significantly different from that of healthy controls, and RTRs had a lower diversity of the gut microbiome (p < 0.01). Proton-pump inhibitors, mycophenolate mofetil, and estimated glomerular filtration rate (eGFR) are significant determinants of the gut microbiome of RTRs (p < 0.05). Use of mycophenolate mofetil correlated to a lower diversity (p < 0.01). Moreover, significant alterations were found in multiple bacterial taxa between RTRs and healthy controls. The gut microbiome of RTRs contained more Proteobacteria and less Actinobacteria, and there was a loss of butyrate-producing bacteria in the gut microbiome of RTRs. By comparing the gut microbiome of RTRs to healthy controls we have shown that RTRs suffer from dysbiosis, a disruption in the balance of the gut microbiome.}, }
@article {pmid32023967, year = {2020}, author = {Kachrimanidou, M and Tsintarakis, E}, title = {Insights into the Role of Human Gut Microbiota in Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, pmid = {32023967}, issn = {2076-2607}, abstract = {Clostridioides difficile infection (CDI) has emerged as a major health problem worldwide. A major risk factor for disease development is prior antibiotic use, which disrupts the normal gut microbiota by altering its composition and the gut's metabolic functions, leading to the loss of colonization resistance and subsequent CDI. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with a decreased level of gut microbiota diversity. The investigation of the gut's microbial communities, in both healthy subjects and patients with CDI, elucidate the role of microbiota and improve the current biotherapeutics for patients with CDI. Fecal microbiota transplantation has a major role in managing CDI, aiming at re-establishing colonization resistance in the host gastrointestinal tract by replenishing the gut microbiota. New techniques, such as post-genomics, proteomics and metabolomics analyses, can possibly determine in the future the way in which C. difficile eradicates colonization resistance, paving the way for the development of new, more successful treatments and prevention. The aim of the present review is to present recent data concerning the human gut microbiota with a focus on its important role in health and disease.}, }
@article {pmid32023228, year = {2020}, author = {Pimentel, M and Saad, RJ and Long, MD and Rao, SSC}, title = {ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {2}, pages = {165-178}, doi = {10.14309/ajg.0000000000000501}, pmid = {32023228}, issn = {1572-0241}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Blind Loop Syndrome/*diagnosis/*therapy ; Breath Tests ; Culture Techniques ; *Diet Therapy ; *Fecal Microbiota Transplantation ; Humans ; Hydrogen/analysis ; Intestine, Small ; Methane/analysis ; Probiotics/*therapeutic use ; Suction ; }, abstract = {Small intestinal bacterial overgrowth is defined as the presence of excessive numbers of bacteria in the small bowel, causing gastrointestinal symptoms. This guideline statement evaluates criteria for diagnosis, defines the optimal methods for diagnostic testing, and summarizes treatment options for small intestinal bacterial overgrowth. This guideline provides an evidence-based evaluation of the literature through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the available evidence was not appropriate for a formal GRADE recommendation, key concepts were developed using expert consensus.}, }
@article {pmid32020359, year = {2020}, author = {Lechner, S and Yee, M and Limketkai, BN and Pham, EA}, title = {Fecal Microbiota Transplantation for Chronic Liver Diseases: Current Understanding and Future Direction.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {897-905}, pmid = {32020359}, issn = {1573-2568}, mesh = {Chronic Disease ; Fecal Microbiota Transplantation/methods/*trends ; Forecasting ; Gastrointestinal Microbiome/*physiology ; Humans ; Liver Diseases/*microbiology/pathology/*therapy ; }, abstract = {Chronic liver disease is a major cause of morbidity and mortality worldwide. Even though effective treatments are now available for most chronic viral hepatitis, treatment options for other causes of chronic liver disease remain inadequate. Recent research has revealed a previously unappreciated role that the human intestinal microbiome plays in mediating the development and progression of chronic liver diseases. The recent remarkable success of fecal microbiota transplantation (FMT) in treating Clostridioides difficile demonstrates that the intestinal microbiota can be manipulated to obtain favorable therapeutic benefits and that FMT may become an important component of a total therapeutic approach to effectively treat hepatic disorders.}, }
@article {pmid32019832, year = {2020}, author = {Ghimire, S and Roy, C and Wongkuna, S and Antony, L and Maji, A and Keena, MC and Foley, A and Scaria, J}, title = {Identification of Clostridioides difficile-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {32019832}, issn = {2379-5077}, abstract = {A major function of the gut microbiota is to provide colonization resistance, wherein pathogens are inhibited or suppressed below infectious levels. However, the fraction of gut microbiota required for colonization resistance remains unclear. We used culturomics to isolate a gut microbiota culture collection comprising 1,590 isolates belonging to 102 species. This culture collection represents 34.57% of the taxonomic diversity and 70% functional capacity, as estimated by metagenomic sequencing of the fecal samples used for culture. Using whole-genome sequencing, we characterized species representatives from this collection and predicted their phenotypic traits, further characterizing isolates by defining nutrient utilization profiles and short-chain fatty acid production. When screened with a coculture assay, 66 species in our culture collection inhibited Clostridioides difficile Several phenotypes, particularly, growth rate, production of SCFAs, and the utilization of mannitol, sorbitol, or succinate, correlated with C. difficile inhibition. We used a combinatorial community assembly approach to formulate defined bacterial mixes inhibitory to C. difficile We tested 256 combinations and found that both species composition and blend size were important in inhibition. Our results show that the interaction of bacteria with one another in a mix and with other members of gut commensals must be investigated to design defined bacterial mixes for inhibiting C. difficile in vivo IMPORTANCE Antibiotic treatment causes instability of gut microbiota and the loss of colonization resistance, thus allowing pathogens such as Clostridioides difficile to colonize and causing recurrent infection and mortality. Although fecal microbiome transplantation has been shown to be an effective treatment for C. difficile infection (CDI), a more desirable approach would be the use of a defined mix of inhibitory gut bacteria. The C. difficile-inhibiting species and bacterial combinations identified herein improve the understanding of the ecological interactions controlling colonization resistance against C. difficile and could aid in the design of defined bacteriotherapy as a nonantibiotic alternative against CDI.}, }
@article {pmid32017983, year = {2020}, author = {Nochi, T and Suzuki, S and Ito, S and Morita, S and Furukawa, M and Fuchimoto, D and Sasahara, Y and Usami, K and Niimi, K and Itano, O and Kitago, M and Matsuda, S and Matsuo, A and Suyama, Y and Sakai, Y and Wu, G and Bazer, FW and Watanabe, K and Onishi, A and Aso, H}, title = {Elucidation of the Effects of a Current X-SCID Therapy on Intestinal Lymphoid Organogenesis Using an In Vivo Animal Model.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {10}, number = {1}, pages = {83-100}, pmid = {32017983}, issn = {2352-345X}, mesh = {Adolescent ; Adult ; Animals ; Animals, Genetically Modified ; *Bone Marrow Transplantation ; Child ; Child, Preschool ; Disease Models, Animal ; Female ; Gastrointestinal Microbiome/immunology ; Gene Knockout Techniques ; Humans ; Immunity, Mucosal ; Immunoglobulin G/blood/immunology ; Interleukin Receptor Common gamma Subunit/*genetics ; Intestinal Mucosa/*growth &amp; development/immunology/microbiology ; Male ; Organogenesis/genetics/immunology ; Peyer's Patches/*growth &amp; development/immunology ; Swine ; Treatment Outcome ; X-Linked Combined Immunodeficiency Diseases/genetics/immunology/pathology/*therapy ; }, abstract = {BACKGROUND &amp; AIMS: Organ-level research using an animal model lacking Il2rg, the gene responsible for X-linked severe combined immunodeficiency (X-SCID), is clinically unavailable and would be a powerful tool to gain deeper insights into the symptoms of patients with X-SCID.<br><br>METHODS: We used an X-SCID animal model, which was first established in our group by the deletion of Il2rg gene in pigs, to understand the clinical signs from multiple perspectives based on pathology, immunology, microbiology, and nutrition. We also treated the X-SCID pigs with bone marrow transplantation (BMT) for mimicking a current therapeutic treatment for patients with X-SCID and investigated the effect at the organ-level. Moreover, the results were confirmed using serum and fecal samples collected from patients with X-SCID.<br><br>RESULTS: We demonstrated that X-SCID pigs completely lacked Peyer's patches (PPs) and IgA production in the small intestine, but possessed some dysfunctional intestinal T and B cells. Another novel discovery was that X-SCID pigs developed a heterogeneous intestinal microflora and possessed abnormal plasma metabolites, indicating that X-SCID could be an immune disorder that affects various in&#xa0;vivo functions. Importantly, the organogenesis of PPs in X-SCID pigs was not promoted by BMT. Although a few isolated lymphoid follicles developed in the small intestine of BMT-treated X-SCID pigs, there was no evidence that they contributed to IgA production and microflora formation. Consistently, most patients with X-SCID who received BMT possessed abnormal intestinal immune and microbial environments regardless of the presence of sufficient serum IgG.<br><br>CONCLUSIONS: These results indicate that the current BMT therapies for patients with X-SCID may be insufficient to induce the organogenesis of intestinal lymphoid tissues that are associated with numerous functions in&#xa0;vivo.}, }
@article {pmid32017248, year = {2020}, author = {You, JHS and Jiang, X and Lee, WH and Chan, PKS and Ng, SC}, title = {Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with inflammatory bowel disease.}, journal = {Journal of gastroenterology and hepatology}, volume = {35}, number = {9}, pages = {1515-1523}, doi = {10.1111/jgh.15002}, pmid = {32017248}, issn = {1440-1746}, mesh = {Antibodies, Monoclonal/administration &amp; dosage ; Broadly Neutralizing Antibodies/administration &amp; dosage ; Clostridium Infections/*economics/*therapy ; *Cost-Benefit Analysis ; *Costs and Cost Analysis ; Fecal Microbiota Transplantation/*economics ; Fidaxomicin/administration &amp; dosage ; Health Personnel ; Hong Kong ; Humans ; Inflammatory Bowel Diseases/*economics/*therapy ; Public Health ; Quality-Adjusted Life Years ; Recurrence ; Treatment Outcome ; Vancomycin/administration &amp; dosage ; }, abstract = {BACKGROUND AND AIM: Inflammatory bowel disease (IBD) patients are at risk for recurrent Clostridium difficile infection (RCDI). We aimed to evaluate the potential health economic and clinical outcomes of four strategies for management of RCDI in IBD patients from the perspective of public health-care provider in Hong Kong.<br><br>METHODS: A decision-analytic model was designed to simulate outcomes of adult IBD patients with first RCDI treated with vancomycin, vancomycin plus bezlotoxumab, fidaxomicin and fecal microbiota transplantation (FMT). Model inputs were derived from literature and public data. Primary model outcomes were C.&#xa0;difficile infection (CDI)-related direct medical cost and quality-adjusted life-years (QALYs) loss. Base-case and sensitivity analysis were performed.<br><br>RESULTS: Comparing to vancomycin, fidaxomicin and vancomycin plus bezlotoxumab, FMT saved 0.00318, 0.00149 and 0.00306 QALYs and reduced cost by USD3180, USD3790 and USD5514, respectively, in base-case analysis. In probabilistic sensitivity analysis, FMT was cost-saving when comparing to vancomycin, fidaxomicin and vancomycin plus bezlotoxumab by USD3765 (95% confidence interval [CI] 3732-3798; P&#xa0;<&#xa0;0.001), USD3854 (95%CI 3827-3883; P&#xa0;<&#xa0;0.001) and USD6501 (95%CI 6465-6,536; P&#xa0;<&#xa0;0.001), respectively. The QALYs saved by FMT (vs vancomycin) were 0.00386 QALYs (95%CI 0.00384-0.00388; P&#xa0;<&#xa0;0.001), (vs fidaxomicin) 0.00179 QALYs (95%CI 0.00177-0.00180; P&#xa0;<&#xa0;0.001) and (vs vancomycin plus bezlotoxumab) 0.00376 QALYs (95%CI 0.00374-0.00378; P&#xa0;<&#xa0;0.001). FMT was found to save QALYs at lower cost in 99.3% (vs vancomycin), 99.7% (vs fidaxomicin) and 100.0% (vs vancomycin plus bezlotoxumab) of the 10&#xa0;000 Monte Carlo simulations.<br><br>CONCLUSIONS: FMT for IBD patients with RCDI appeared to save both direct medical cost and QALYs when comparing to vancomycin (with or without bezlotoxumab) and fidaxomicin.}, }
@article {pmid32016290, year = {2020}, author = {Peng, Y and Thomas, AS and Wei, D and Tan, D and Wang, Y}, title = {An Aggressive Approach Toward a Case of Refractory Ulcerative Colitis With Uncertain Etiology in the Context of Chronic Myeloid Leukemia.}, journal = {Inflammatory bowel diseases}, volume = {26}, number = {4}, pages = {e26-e27}, doi = {10.1093/ibd/izaa016}, pmid = {32016290}, issn = {1536-4844}, mesh = {Aged ; Colitis, Ulcerative/*pathology/*therapy ; Colonoscopy ; Dasatinib/administration &amp; dosage ; Fatal Outcome ; Fecal Microbiota Transplantation ; Humans ; Imatinib Mesylate/administration &amp; dosage ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy ; Male ; }, }
@article {pmid32015948, year = {2020}, author = {Li, B and Yin, GF and Wang, YL and Tan, YM and Huang, CL and Fan, XM}, title = {Impact of fecal microbiota transplantation on TGF-β1/Smads/ERK signaling pathway of endotoxic acute lung injury in rats.}, journal = {3 Biotech}, volume = {10}, number = {2}, pages = {52}, pmid = {32015948}, issn = {2190-572X}, abstract = {Acute lung injury (ALI) is a common clinical disease with high morbidity in both humans and animals. Studies have shown that intestinal microbiota affect the pathology and immune function of respiratory diseases through the "gut-lung axis". The authors investigated the therapeutic effect of fecal microbiota transplantation (FMT) in rats with ALI induced by lipopolysaccharide (LPS). Rats were treated with FMT, and then measured lung wet/dry ratio, PaO2 in artery, proinflammatory marker, and TGF-β1, Smad3, Smad7, and phosphorylated ERK (p-ERK) protein levels, as well as a histopathologic analysis and high-throughput sequencing of intestinal microbiota. FMT significantly reduced lung wet/dry ratio and TNF-α, IL-1β, and IL-6 levels, but increased the levels of PaO2 in artery. In addition, FMT significantly decreased the expression of TGF-β1, Smad3, and p-ERK, while increased the levels of Smad7. Lung histopathological analyses showed that FMT reduced the inflammatory cell infiltration and interstitial lung exudates. High-throughput sequencing of intestinal microbiota analyses showed that FMT reconstructed the structure of intestinal microbiota, and increased the gene abundance of the bacterial community. Therefore, FMT may act on the TGF-β1/Smads/ERK pathway by regulating intestinal microbiota, inhibiting immune inflammation, reducing the production of inflammatory markers in the body and release, and reducing alveolar epithelial damage and repair, thereby improving the endotoxic ALI in rats induced by LPS.}, }
@article {pmid32014035, year = {2020}, author = {Sokol, H and Landman, C and Seksik, P and Berard, L and Montil, M and Nion-Larmurier, I and Bourrier, A and Le Gall, G and Lalande, V and De Rougemont, A and Kirchgesner, J and Daguenel, A and Cachanado, M and Rousseau, A and Drouet, &#xc9; and Rosenzwajg, M and Hagege, H and Dray, X and Klatzman, D and Marteau, P and ,  and Beaugerie, L and Simon, T}, title = {Fecal microbiota transplantation to maintain remission in Crohn's disease: a pilot randomized controlled study.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {12}, pmid = {32014035}, issn = {2049-2618}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Adult ; Crohn Disease/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Male ; Microbiota ; Pilot Projects ; Remission Induction ; Research Design ; Severity of Illness Index ; Single-Blind Method ; Treatment Outcome ; }, abstract = {BACKGROUND: The role of the gut microbiota in Crohn's disease (CD) is established and fecal microbiota transplantation (FMT) is an attractive therapeutic strategy. No randomized controlled clinical trial results are available. We performed a randomized, single-blind, sham-controlled pilot trial of FMT in adults with colonic or ileo-colonic CD.<br><br>METHOD: Patients enrolled while in flare received oral corticosteroid. Once in clinical remission, patients were randomized to receive either FMT or sham transplantation during a colonoscopy. Corticosteroids were tapered and a second colonoscopy was performed at week 6. The primary endpoint was the implantation of the donor microbiota at week 6 (Sorensen index > 0.6).<br><br>RESULTS: Eight patients received FMT and nine sham transplantation. None of the patients reached the primary endpoint. The steroid-free clinical remission rate at 10 and 24&#x2009;weeks was 44.4% (4/9) and 33.3% (3/9) in the sham transplantation group and 87.5% (7/8) and 50.0% (4/8; one patient loss of follow-up while in remission at week 12 and considered in flare at week 24) in the FMT group. Crohn's Disease Endoscopic Index of Severity decreased 6&#x2009;weeks after FMT (p = 0.03) but not after sham transplantation (p = 0.8). Conversely, the CRP level increased 6&#x2009;weeks after sham transplantation (p = 0.008) but not after FMT (p = 0.5). Absence of donor microbiota engraftment was associated with flare. No safety signal was identified.<br><br>CONCLUSION: The primary endpoint was not reached for any patient. In this pilot study, higher colonization by donor microbiota was associated with maintenance of remission. These results must be confirmed in larger studies (NCT02097797). Video abstract.}, }
@article {pmid32011405, year = {2020}, author = {Perler, BK and Chen, B and Phelps, E and Allegretti, JR and Fischer, M and Ganapini, V and Krajiceck, E and Kumar, V and Marcus, J and Nativ, L and Kelly, CR}, title = {Long-Term Efficacy and Safety of Fecal Microbiota Transplantation for Treatment of Recurrent Clostridioides difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {54}, number = {8}, pages = {701-706}, doi = {10.1097/MCG.0000000000001281}, pmid = {32011405}, issn = {1539-2031}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {GOALS: We investigated the long-term efficacy and safety of fecal microbiota transplant (FMT) for the treatment of recurrent Clostridioides difficile infection (rCDI).<br><br>BACKGROUND: FMT has emerged as a promising therapy for patients with rCDI unresponsive to standard medical therapy, though long-term efficacy and safety data are scarce.<br><br>MATERIALS AND METHODS: A multicenter retrospective study was performed on patients treated with FMT for rCDI with &#x2265;6 months of clinical follow-up post-FMT. Patients were contacted to document sustained efficacy, potential adverse events, and antibiotic exposure. The electronic medical record was reviewed to confirm patient-reported outcomes and obtain additional data. The primary outcome was sustained cure, as defined by the absence of Clostridioides difficile infection (CDI) at any timepoint after FMT.<br><br>RESULTS: Of 528 patients treated, 207 were successfully contacted. The mean follow-up post-FMT was 34 (range: 6 to 84) months. One hundred fifty-seven patients (75.8%) reported sustained cure at the time of follow-up. One hundred patients (48%) reported the use of antibiotics for non-CDI indications post-FMT, of whom 11 (11%) had experienced CDI post-FMT. Fifty-two of the original 528 patients (9.8%) treated with FMT had died at the time of follow-up contact; none were felt attributable to the procedure. New medical conditions or diagnoses post-FMT were reported in 105 patients (50.5%). Fifteen reported improvement post-FMT in previously diagnosed medical conditions.<br><br>CONCLUSIONS: In this largest and longest study to date on efficacy and safety after FMT for treatment of rCDI, we found that the majority of patients experienced long-term cure. Although a number of new conditions developed post-FMT, there was no clustering of diseases associated with dysbiosis.}, }
@article {pmid32010641, year = {2019}, author = {Wang, H and Lu, Y and Yan, Y and Tian, S and Zheng, D and Leng, D and Wang, C and Jiao, J and Wang, Z and Bai, Y}, title = {Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {455}, pmid = {32010641}, issn = {2235-2988}, mesh = {Animals ; Apoptosis ; Blood Glucose/metabolism ; Cytokines ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2/*therapy ; Diet, High-Fat ; Energy Metabolism ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/genetics/physiology ; Glycated Hemoglobin ; Inflammation/pathology ; Insulin/metabolism ; *Insulin Resistance ; Islets of Langerhans/pathology ; Mice ; }, abstract = {Type 2 diabetes is a common metabolic disorder related to insulin resistance, or deficiency of insulin secretion, caused by decreased insulin sensitivity and destruction of islet structure and function. As the second human genome, the microbiota has been observed to have a growing relationship with diabetes in recent years. Microbiota imbalance has been hypothesized to be involved in the regulation of energy metabolism and the inflammatory immune response in diabetes. The present study aimed to investigate whether fecal microbiota transplantation (FMT) could alleviate the symptoms associated with type 2 diabetes. To this end, a type 2 diabetes mouse model was first established through the consumption of a high-fat diet combined with streptozotocin (100 mg/kg), and FMT was used to rebuild the gut microbiota of diabetic mice. Fasting blood glucose, oral glucose tolerance tests, and HbA1c levels were monitored, while the hypoglycemic effects of FMT were also observed. Insulin levels were tested by ELISA and related indexes such as HOMA-IR, HOMA-IS, and HOMA-β were calculated. We found that insulin resistance and pancreatic islet β-cells were improved after FMT treatment. Meanwhile, the markers of inflammation in the pancreatic tissue were detected by ELISA and immunohistochemistry, which indicated that inflammatory response decreased following FMT treatment. Furthermore, flow cytometry and western blot results revealed that FMT inhibited the β-cell apoptosis. Here, the effect of FMT on hypoglycemia in type 2 diabetes was addressed by improving insulin resistance and repairing impaired islets, thereby providing a potential treatment strategy for type 2 diabetes.}, }
@article {pmid32010434, year = {2020}, author = {Zama, D and Bossù, G and Leardini, D and Muratore, E and Biagi, E and Prete, A and Pession, A and Masetti, R}, title = {Insights into the role of intestinal microbiota in hematopoietic stem-cell transplantation.}, journal = {Therapeutic advances in hematology}, volume = {11}, number = {}, pages = {2040620719896961}, pmid = {32010434}, issn = {2040-6207}, abstract = {The gut microbiota (GM) is able to modulate the human immune system. The development of novel investigation methods has provided better characterization of the GM, increasing our knowledge of the role of GM in the context of hematopoietic stem-cell transplantation (HSCT). In particular, the GM influences the development of the major complications seen after HSCT, having an impact on overall survival. In fact, this evidence highlights the possible therapeutic implications of modulation of the GM during HSCT. Insights into the complex mechanisms and functions of the GM are essential for the rational design of these therapeutics. To date, preemptive and curative approaches have been tested. The current state of understanding of the impact of the GM on HSCT, and therapies targeting the GM balance is reviewed herein.}, }
@article {pmid32009472, year = {2021}, author = {Zhou, HY and Guo, B and Lufumpa, E and Li, XM and Chen, LH and Meng, X and Li, BZ}, title = {Comparative of the Effectiveness and Safety of Biological Agents, Tofacitinib, and Fecal Microbiota Transplantation in Ulcerative Colitis: Systematic Review and Network Meta-Analysis.}, journal = {Immunological investigations}, volume = {50}, number = {4}, pages = {323-337}, doi = {10.1080/08820139.2020.1714650}, pmid = {32009472}, issn = {1532-4311}, mesh = {Antibodies, Monoclonal/adverse effects/*therapeutic use ; Biological Factors/adverse effects/*therapeutic use ; Colitis, Ulcerative/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Janus Kinase Inhibitors/adverse effects/*therapeutic use ; Network Meta-Analysis ; Piperidines/adverse effects/*therapeutic use ; Pyrimidines/adverse effects/*therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Biological agents are commonly used for the treatment of ulcerative colitis (UC). As new treatments, tofacitinib, and fecal microbiota transplantation (FMT) have demonstrated efficacy in treating UC. This network meta-analysis aims to determine the efficacy and safety of biological agents, tofacitinib, and FMT.<br><br>METHODS: A network meta-analysis was conducted by systematically searching the PubMed, Embase, and Cochrane Libraries. According to strict inclusion and exclusion criteria, we included randomized controlled trials (RCTs) of biological agents, tofacitinib, and FMT in UC. A random-effect model was chosen by the network meta-analysis and sensitivity analysis. Heterogeneity test and publication bias test were performed to determine the efficacy of treatments.<br><br>RESULTS: Data were extracted from 16 RCTs and we found that all treatments were more effective than the placebos. A total of 21 comparisons were made to determine efficiency. We found that infliximab, vedolizumab, and FMT performed better curative effect in terms of absolute effects and relative ranks. Furthermore, there was no statistical difference in the efficacy of biological agents, tofacitinib, and FMT. Moreover, no treatments were found to increase the occurrence of adverse events when compared with placebos, except infliximab. However, vedolizumab seemed to reduce the occurrence of adverse events compared with infliximab.<br><br>CONCLUSION: Of the biological agents, vedolizumab and infliximab were the most effective, suggesting that biological agents are still a better choice. Nevertheless, tofacitinib and FMT may be promising alternatives with high efficacies. However, more safety and maintenance studies need to be conducted in future for the acquisition of more accurate results.Abbreviations: FMT: Fecal microbiota transplantation; UC: Ulcerative colitis; RCTs: Randomized controlled trials; IBD: Inflammatory bowel disease; CD: Crohn's disease; IBS: Irritable bowel syndrome; CDI: Clostridium difficile infections; ITT: Intention-to-treat; RR: Relative risk; CI: Confidence interval; CrI: Credible intervals; IFX: Infliximab; ADA: Adalimumab; TFB: Tofacitinib; GLM: Golimumab; VDZ: Vedolizumab; PBO: Placebo; wk: week; F: Female; M: Male; AEs: Adverse events; SAEs: Serious adverse events; anti-TNF: Anti-tumor necrosis factors.}, }
@article {pmid32009331, year = {2020}, author = {Gaj, F and Biviano, I and Trecca, A and Lai, Q and Andreuccetti, J}, title = {Early and late effects of the sequential transfixed stich technique for the treatment of the symptomatic rectocele without rectal mucosa prolapse.}, journal = {Minerva chirurgica}, volume = {75}, number = {2}, pages = {83-91}, doi = {10.23736/S0026-4733.20.08175-4}, pmid = {32009331}, issn = {1827-1626}, mesh = {Adult ; Aged ; Female ; Humans ; Intestinal Mucosa ; Middle Aged ; Postoperative Complications/epidemiology ; Rectal Prolapse ; Rectocele/diagnosis/*surgery ; *Suture Techniques ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Different surgical techniques have been proposed for rectocele repair. However, controversial aspects exist on the best approach to use. The study aims to report the early and late outcomes of the sequential transfixed stich technique (STST) for the treatment of rectocele in the absence of mucosal prolapse.<br><br>METHODS: One hundred patients presenting a symptomatic rectocele were treated with STST from January 2010 through August 2015. Patients with mucosal prolapse were not considered eligible for STST. After a period of 24 months from surgery, all the patients were clinically evaluated with the intent to investigate the risk of recurrence of the preoperative symptoms.<br><br>RESULTS: All the patients were women (median age=54.7 years; ranges=37-75). Median discharge time was 1.5 days. One-month severe complications were: hemorrhoid thrombosis (6.0%), self-solved bleeding (6.0%), urinary retention (4.0%), anal secretion (4.0%) and urinary incontinence (1.0%). No post-operative cases of fecal incontinence were observed. Two years after surgery, 76.0% of patients reported a global improvement of the preoperative symptoms, with 73 and 35% of cases showing a reduced difficulty in the evacuation and need for digitation. Only 8.0% of patients showed a recurrence of the initial symptoms.<br><br>CONCLUSIONS: The STST is a feasible, safe, and cost-effective technique for the treatment of the rectocele without rectal mucosal prolapse. The method does not increase the risk of postoperative anal incontinence and presents a short hospital stay. STST presents long-term results in line with other transvaginal and transanal approaches.}, }
@article {pmid32008133, year = {2020}, author = {DuPont, HL and Jiang, ZD and DuPont, AW and Utay, NS}, title = {Abnormal Intestinal Microbiome in Medical Disorders and Potential Reversibility by Fecal Microbiota Transplantation.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {741-756}, pmid = {32008133}, issn = {1573-2568}, mesh = {Fecal Microbiota Transplantation/*methods/trends ; Gastrointestinal Diseases/*microbiology/*therapy ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology/*physiology ; Humans ; Living Donors ; }, abstract = {Reduction in diversity of the intestinal microbiome (dysbiosis) is being identified in many disease states, and studies are showing important biologic contributions of microbiome to health and disease. Fecal microbiota transplantation (FMT) is being evaluated as a way to reverse dysbiosis in diseases and disorders in an attempt to improve health. The published literature was reviewed to determine the value of FMT in the treatment of medical disorders for which clinical trials have recently been conducted. FMT is effective in treating recurrent C. difficile infection in one or two doses, with many healthy donors providing efficacious fecal-derived products. In inflammatory bowel disease (IBD), FMT may lead to remission in approximately one-third of moderate-to-severe illnesses with one study suggesting that more durable FMT responses may be seen when used once medical remissions have been achieved. Donor products differ in their efficacy in treatment of IBD. Combining donor products has been one way to increase the potential value of FMT in treating chronic disorders. FMT is being explored in a variety of clinical settings affecting different organ systems outside CDI, with positive preliminary signals, in treatment of functional constipation, immunotherapy-induced colitis, neurodegenerative disease, as well as prevention of cancer-related disorders like graft versus host disease and decolonization of patients with recurrent urinary tract infection due to antibiotic-resistant bacteria. Currently, intense research is underway to see how the microbiome products like FMT can be harnessed for health benefits.}, }
@article {pmid32006212, year = {2020}, author = {Oka, A and Sartor, RB}, title = {Microbial-Based and Microbial-Targeted Therapies for Inflammatory Bowel Diseases.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {757-788}, pmid = {32006212}, issn = {1573-2568}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/adverse effects ; Dysbiosis/microbiology/therapy ; *Fecal Microbiota Transplantation/trends ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Prebiotics/*administration &amp; dosage/microbiology ; Probiotics/*administration &amp; dosage ; Randomized Controlled Trials as Topic/methods ; }, abstract = {Inflammatory bowel diseases (IBD), including Crohn's disease, ulcerative colitis, and pouchitis, are chronic, relapsing intestinal inflammatory disorders mediated by dysregulated immune responses to resident microbiota. Current standard therapies that block immune activation with oral immunosuppressives or biologic agents are generally effective, but each therapy induces a sustained remission in only a minority of patients. Furthermore, these approaches can have severe adverse events. Recent compelling evidence of a role of unbalanced microbiota (dysbiosis) driving immune dysfunction and inflammation in IBD supports the therapeutic rationale for manipulating the dysbiotic microbiota. Traditional approaches using currently available antibiotics, probiotics, prebiotics, and synbiotics have not produced optimal results, but promising outcomes with fecal microbiota transplant provide a proof of principle for targeting the resident microbiota. Rationally designed oral biotherapeutic products (LBPs) composed of mixtures of protective commensal bacterial strains demonstrate impressive preclinical results. Resident microbial-based and microbial-targeted therapies are currently being studied with increasing intensity for IBD primary therapy with favorable early results. This review presents current evidence and therapeutic mechanisms of microbiota modulation, emphasizing clinical studies, and outlines prospects for future IBD treatment using new approaches, such as LBPs, bacteriophages, bacterial function-editing substrates, and engineered bacteria. We believe that the optimal clinical use of microbial manipulation may be as adjuvants to immunosuppressive for accelerated and improved induction of deep remission and as potential safer solo approaches to sustained remission using personalized regimens based on an individual patient's microbial profile.}, }
@article {pmid32004847, year = {2020}, author = {Dong, T and Guan, Q and Hu, W and Zhang, M and Zhang, Y and Chen, M and Wang, X and Xia, Y}, title = {Prenatal exposure to glufosinate ammonium disturbs gut microbiome and induces behavioral abnormalities in mice.}, journal = {Journal of hazardous materials}, volume = {389}, number = {}, pages = {122152}, doi = {10.1016/j.jhazmat.2020.122152}, pmid = {32004847}, issn = {1873-3336}, mesh = {Aminobutyrates/*toxicity ; Animals ; Behavior, Animal/drug effects ; Behavioral Symptoms/*chemically induced/prevention &amp; control ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects ; Herbicides/*toxicity ; Locomotion/drug effects ; Male ; Maternal Exposure ; Mice, Inbred ICR ; Pregnancy ; Prenatal Exposure Delayed Effects ; Psychomotor Disorders/*chemically induced/prevention &amp; control ; Social Interaction/drug effects ; Water Pollutants, Chemical/*toxicity ; }, abstract = {Glufosinate ammonium (GLA) is a widely used organophosphate herbicide, which could be commonly detected in body fluids of both pregnant women and newborns. Existing evidences indicate that GLA has reproductive toxicity, while data concerning the effects of prenatal GLA exposure on neurodevelopment is rather limited. Here we employed a mouse model exposed to GLA prenatally. Reduced locomotor activity, impaired memory formation and autism-like behaviors were observed in the treatment group. Marked alteration in gut microbiome of the treatment offspring mice could be found at 4th week, and seemed to recover over time. Fecal metabolomics analysis indicated remarkable changes in microbiome-related metabolism in the treatment group, which could be the cause of behavioral abnormality in mice. Present study suggested that prenatal exposure to GLA disturbed gut microbiome and metabolism, and thereby induced behavioral abnormalities in mice.}, }
@article {pmid32004593, year = {2020}, author = {Bajaj, JS and Khoruts, A}, title = {Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis.}, journal = {Journal of hepatology}, volume = {72}, number = {5}, pages = {1003-1027}, doi = {10.1016/j.jhep.2020.01.017}, pmid = {32004593}, issn = {1600-0641}, support = {R21 TR002024/TR/NCATS NIH HHS/United States ; R01 HS025412/HS/AHRQ HHS/United States ; }, mesh = {Adult ; Animals ; Anti-Bacterial Agents/therapeutic use ; Disease Models, Animal ; Dysbiosis/*drug therapy ; Fecal Microbiota Transplantation/*adverse effects/*methods ; Female ; Gastrointestinal Agents/therapeutic use ; *Gastrointestinal Microbiome ; Hepatic Encephalopathy/drug therapy ; Humans ; Liver Cirrhosis/*drug therapy/*microbiology ; Male ; Mice ; Probiotics/therapeutic use ; Proton Pump Inhibitors/therapeutic use ; Treatment Outcome ; }, abstract = {Patients with chronic liver disease and cirrhosis demonstrate a global mucosal immune impairment, which is associated with altered gut microbiota composition and functionality. These changes progress along with the advancing degree of cirrhosis and can be linked with hepatic encephalopathy, infections and even prognostication independent of clinical biomarkers. Along with compositional changes, functional alterations to the microbiota, related to short-chain fatty acids, bioenergetics and bile acid metabolism, are also associated with cirrhosis progression and outcomes. Altering the functional and structural profile of the microbiota is partly achieved by medications used in patients with cirrhosis such as rifaximin, lactulose, proton pump inhibitors and other antibiotics. However, the role of faecal or intestinal microbiota transplantation is increasingly being recognised. Herein, we review the challenges, opportunities and road ahead for the appropriate and safe use of intestinal microbiota transplantation in liver disease.}, }
@article {pmid32004516, year = {2020}, author = {Ramos-Martínez, A and Martínez-Ruiz, R and Múñez-Rubio, E and Valencia-Alijo, A and Ferre-Aracil, C and Vera-Mendoza, MI}, title = {Effect of faecal microbiota transplantation on recurrent urinary tract infection in a patient with long-term suprapubic urinary catheter.}, journal = {The Journal of hospital infection}, volume = {105}, number = {2}, pages = {332-333}, doi = {10.1016/j.jhin.2020.01.016}, pmid = {32004516}, issn = {1532-2939}, mesh = {Adult ; *Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; Urinary Catheters/*adverse effects/microbiology ; Urinary Tract Infections/*therapy ; }, }
@article {pmid32003951, year = {2020}, author = {Mounsey, A and Lacy Smith, K and Reddy, VC and Nickolich, S}, title = {Clostridioides difficile Infection: Update on Management.}, journal = {American family physician}, volume = {101}, number = {3}, pages = {168-175}, pmid = {32003951}, issn = {1532-0650}, mesh = {Adult ; Age Factors ; Aged ; Anti-Bacterial Agents/administration &amp; dosage ; Antimicrobial Stewardship ; Child ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/*diagnosis/physiopathology/*prevention &amp; control ; Fidaxomicin/administration &amp; dosage ; Humans ; Infant ; Practice Guidelines as Topic ; Risk Factors ; Severity of Illness Index ; Vancomycin/administration &amp; dosage ; }, abstract = {Guidelines for the diagnosis and treatment of Clostridioides difficile infection have recently been updated. Risk factors include recent exposure to health care facilities or antibiotics, especially clindamycin. C. difficile infection is characterized by a wide range of symptoms, from mild or moderate diarrhea to severe disease with pseudomembranous colitis, colonic ileus, toxic megacolon, sepsis, or death. C. difficile infection should be considered in patients who are not taking laxatives and have three or more episodes of unexplained, unformed stools in 24 hours. Testing in these patients should start with enzyme immunoassays for glutamate dehydrogenase and toxins A and B or nucleic acid amplification testing. In children older than 12 months, testing is recommended only for those with prolonged diarrhea and risk factors. Treatment depends on whether the episode is an initial vs. recurrent infection and on the severity of the infection based on white blood cell count, serum creatinine level, and other clinical signs and symptoms. For an initial episode of nonsevere C. difficile infection, oral vancomycin or oral fidaxomicin is recommended. Metronidazole is no longer recommended as first-line therapy for adults. Fecal microbiota transplantation is a reasonable treatment option with high cure rates in patients who have had multiple recurrent episodes and have received appropriate antibiotic therapy for at least three of the episodes. Good antibiotic stewardship is a key strategy to decrease rates of C. difficile infection. In routine or endemic settings, hands should be cleaned with either soap and water or an alcohol-based product, but during outbreaks soap and water is superior. The Infectious Diseases Society of America does not recommend the use of probiotics for prevention of C. difficile infection.}, }
@article {pmid32001562, year = {2020}, author = {Faleye, TOC and George, UE and Simsek, C and Arowolo, OA and Adewumi, OM and Matthijnssens, J and Adeniji, JA}, title = {Reference Human Rotavirus A Genome Sequence from a Previously Vaccinated Child with Diarrhea in Nigeria.}, journal = {Microbiology resource announcements}, volume = {9}, number = {5}, pages = {}, pmid = {32001562}, issn = {2576-098X}, abstract = {In 2018, a 26-month-old girl, fully vaccinated with Rotarix in 2016, presented with fever, diarrhea, and vomiting. A rapid test showed that her feces contained rotavirus A (RVA). VP7 reverse transcription-PCR (RT-PCR) and Illumina sequencing showed that a G1P[8] strain with a Wa-like genotype constellation was the etiologic agent. This is the first near-complete RVA genome sequence from Nigeria.}, }
@article {pmid32001342, year = {2020}, author = {Ma, Y and Liu, S and Shu, H and Crawford, J and Xing, Y and Tao, F}, title = {Resveratrol alleviates temporomandibular joint inflammatory pain by recovering disturbed gut microbiota.}, journal = {Brain, behavior, and immunity}, volume = {87}, number = {}, pages = {455-464}, pmid = {32001342}, issn = {1090-2139}, support = {K02 DE023551/DE/NIDCR NIH HHS/United States ; R01 DE022880/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; Inflammation/drug therapy ; Mice ; Pain ; Rats ; Rats, Sprague-Dawley ; Resveratrol/pharmacology ; Temporomandibular Joint ; }, abstract = {Patients with temporomandibular disorders (TMDs) often experience persistent facial pain. However, the treatment of TMD pain is still inadequate. In recent years, the disturbance of gut microbiota has been shown to play an important role in the pathogenesis of different neurological diseases including chronic pain. In the present study, we investigated the involvement of gut microbiota in the development of temporomandibular joint (TMJ) inflammation. Intra-temporomandibular joint injection of complete Freund's adjuvant (CFA) was employed to induce TMJ inflammation. Resveratrol (RSV), a natural bioactive compound with anti-inflammatory property, was used to treat the CFA-induced TMJ inflammation. We observed that CFA injection not only induces persistent joint pain, but also causes the reduction of short-chain fatty acids (SCFAs, including acetic acid, propionic acid and butyric acid) in the gut as well as decreases relevant gut bacteria Bacteroidetes and Lachnospiraceae. Interestingly, systemic administration of RSV (i.p.) dose-dependently inhibits CFA-induced TMJ inflammation, reverses CFA-caused reduction of SCFAs and these gut bacteria. Moreover, CFA injection causes blood-brain barrier (BBB) leakage, activates microglia and enhances tumor necrosis factor alpha (TNFα) release in the spinal trigeminal nucleus caudalis (Sp5C). The RSV treatment restores the BBB integrity, inhibits microglial activation and decreases the release of TNFα in the Sp5C. Furthermore, fecal microbiota transplantation with feces from RSV-treated mice significantly diminishes the CFA-induced TMJ inflammation. Taken together, our results suggest that gut microbiome perturbation is critical for the development of TMJ inflammation and that recovering gut microbiome to normal levels could be a new therapeutic approach for treating such pain.}, }
@article {pmid31996833, year = {2020}, author = {Dolgin, E}, title = {Fighting cancer with microbes.}, journal = {Nature}, volume = {577}, number = {7792}, pages = {S16-S18}, pmid = {31996833}, issn = {1476-4687}, mesh = {Animals ; Bacteria/virology ; Bacteriophages/physiology ; Fecal Microbiota Transplantation/trends ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions/*physiology ; Humans ; Mice ; Neoplasms/*microbiology/*therapy ; }, }
@article {pmid31996829, year = {2020}, author = {Svoboda, E}, title = {Could the gut microbiome be linked to autism?.}, journal = {Nature}, volume = {577}, number = {7792}, pages = {S14-S15}, pmid = {31996829}, issn = {1476-4687}, mesh = {Animals ; Autistic Disorder/*microbiology/therapy ; Biodiversity ; Fecal Microbiota Transplantation/trends ; Gastrointestinal Microbiome/*physiology ; *Host Microbial Interactions ; Humans ; Mice ; }, }
@article {pmid31996393, year = {2020}, author = {Nettleton, JE and Cho, NA and Klancic, T and Nicolucci, AC and Shearer, J and Borgland, SL and Johnston, LA and Ramay, HR and Noye Tuplin, E and Chleilat, F and Thomson, C and Mayengbam, S and McCoy, KD and Reimer, RA}, title = {Maternal low-dose aspartame and stevia consumption with an obesogenic diet alters metabolism, gut microbiota and mesolimbic reward system in rat dams and their offspring.}, journal = {Gut}, volume = {69}, number = {10}, pages = {1807-1817}, pmid = {31996393}, issn = {1468-3288}, support = {MOP115076//CIHR/Canada ; }, mesh = {Adiposity/*drug effects ; Animals ; Animals, Newborn ; *Aspartame/metabolism/pharmacology ; Body Weight/drug effects ; Diet, High-Fat/methods ; Energy Metabolism/*drug effects ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/*drug effects ; Glucose/*metabolism ; Glucose Intolerance/metabolism ; Mice ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Stevia/*metabolism ; Sweetening Agents/metabolism/pharmacology ; }, abstract = {OBJECTIVE: We examined the impact of maternal low-dose aspartame and stevia consumption on adiposity, glucose tolerance, gut microbiota and mesolimbic pathway in obese dams and their offspring.<br><br>DESIGN: Following obesity induction, female Sprague-Dawley rats were allocated during pregnancy and lactation to: (1) high fat/sucrose diet (HFS) +water (obese-WTR); (2) HFS +aspartame (obese-APM; 5-7&#x2009;mg/kg/day); (3) HFS +stevia (obese-STV; 2-3&#x2009;mg/kg/day). Offspring were weaned onto control diet and water and followed until 18 weeks. Gut microbiota and metabolic outcomes were measured in dams and offspring. Cecal matter from offspring at weaning was used for faecal microbiota transplant (FMT) into germ-free (GF) mice.<br><br>RESULTS: Maternal APM and STV intake with a HFS diet increased body fat in offspring at weaning and body weight long-term with APM. Maternal APM/HFS consumption impaired glucose tolerance in male offspring at age 8 weeks and both APM and STV altered faecal microbiota in dams and offspring. Maternal obesity/HFS diet affected offspring adiposity and glucose tolerance more so than maternal LCS consumption at age 12 and 18 weeks. APM and STV altered expression of genes in the mesolimbic reward system that may promote consumption of a palatable diet. GF mice receiving an FMT from obese-APM and obese-STV offspring had greater weight gain and body fat and impaired glucose tolerance compared with obese-WTR.<br><br>CONCLUSION: Maternal low-calorie sweetener consumption alongside HFS may disrupt weight regulation, glucose control and gut microbiota in dams and their offspring most notably in early life despite no direct low-calorie sweetener consumption by offspring.}, }
@article {pmid31993446, year = {2019}, author = {Pilla, R and Suchodolski, JS}, title = {The Role of the Canine Gut Microbiome and Metabolome in Health and Gastrointestinal Disease.}, journal = {Frontiers in veterinary science}, volume = {6}, number = {}, pages = {498}, pmid = {31993446}, issn = {2297-1769}, abstract = {The gut microbiome contributes to host metabolism, protects against pathogens, educates the immune system, and, through these basic functions, affects directly or indirectly most physiologic functions of its host. Molecular techniques have allowed us to expand our knowledge by unveiling a wide range of unculturable bacteria that were previously unknown. Most bacterial sequences identified in the canine gastrointestinal (GI) tract fall into five phyla: Firmicutes, Fusobacteria, Bacteroidetes, Proteobacteria, and Actinobacteria. While there are variations in the microbiome composition along the GI tract, most clinical studies concentrate on fecal microbiota. Age, diet, and many other environmental factors may play a significant role in the maintenance of a healthy microbiome, however, the alterations they cause pale in comparison with the alterations found in diseased animals. GI dysfunctions are the most obvious association with gut dysbiosis. In dogs, intestinal inflammation, whether chronic or acute, is associated with significant differences in the composition of the intestinal microbiota. Gut dysbiosis happens when such alterations result in functional changes in the microbial transcriptome, proteome, or metabolome. Commonly affected metabolites include short-chain fatty acids, and amino acids, including tryptophan and its catabolites. A recently developed PCR-based algorithm termed "Dysbiosis Index" is a tool that allows veterinarians to quantify gut dysbiosis and can be used to monitor disease progression and response to treatment. Alterations or imbalances in the microbiota affect immune function, and strategies to manipulate the gut microbiome may be useful for GI related diseases. Antibiotic usage induces a rapid and significant drop in taxonomic richness, diversity, and evenness. For that reason, a renewed interest has been put on probiotics, prebiotics, and fecal microbiota transplantation (FMT). Although probiotics are typically unable to colonize the gut, the metabolites they produce during their transit through the GI tract can ameliorate clinical signs and modify microbiome composition. Another interesting development is FMT, which may be a promising tool to aid recovery from dysbiosis, but further studies are needed to evaluate its potential and limitations.}, }
@article {pmid31993375, year = {2019}, author = {Albouery, M and Buteau, B and Grégoire, S and Cherbuy, C and Pais de Barros, JP and Martine, L and Chain, F and Cabaret, S and Berdeaux, O and Bron, AM and Acar, N and Langella, P and Bringer, MA}, title = {Age-Related Changes in the Gut Microbiota Modify Brain Lipid Composition.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {444}, pmid = {31993375}, issn = {2235-2988}, mesh = {Age Factors ; Aging/*metabolism ; Animals ; Brain/*metabolism ; Cholesterol/metabolism ; Fatty Acid Desaturases/genetics ; Fatty Acid Elongases/genetics ; Fatty Acids/metabolism ; Fatty Acids, Monounsaturated/metabolism ; Fatty Acids, Unsaturated/metabolism ; Gastrointestinal Microbiome/genetics/*physiology ; Gene Expression ; Germ-Free Life ; *Lipid Metabolism ; Lipids ; Liver/metabolism ; Male ; Mice ; Stearoyl-CoA Desaturase/genetics ; }, abstract = {Understanding the molecular mechanisms underlying the changes observed during aging is a prerequisite to design strategies to prevent age-related diseases. Aging is associated with metabolic changes, including alteration in the brain lipid metabolism. These alterations may contribute to the development of pathophysiological conditions. Modifications in the gut microbiota composition are also observed during aging. As communication axes exist between the gut microbiota and the brain and knowing that microbiota influences the host metabolism, we speculated on whether age-associated modifications in the gut microbiota could be involved in the lipid changes observed in aging brain. For that purpose, germ-free mice were colonized by the fecal microbiota of young or old donor mice. Lipid classes and fatty acid profiles were determined in the brain (cortex), plasma and liver by thin-layer chromatography on silica gel-coated quartz rods and gas chromatography. Gut colonization by microbiota of old mice resulted in a significant increase in total monounsaturated fatty acids (MUFA) and a significant decrease in the relative amounts of cholesterol and total polyunsaturated fatty acids (PUFA) in the cortex. Among the eight most represented fatty acids in the cortex, the relative abundances of five (C18:1n-9, C22:6n-3, C20:4n-6, C18:1n-7, and C20:1n-9) were significantly altered in mice inoculated with an aged microbiota. Liquid chromatography analyses revealed that the relative abundance of major species among phosphatidyl and plasmenylcholine (PC 16:0/18:1), phosphatidyl and plasmenylethanolamine (PE 18:0/22:6), lysophosphatidylethanolamine (LPE 22:6) and sphingomyelins (SM d18:1/18:0) were significantly altered in the cortex of mice colonized by the microbiota obtained from aged donors. Transplantation of microbiota from old mice also modified the lipid class and fatty acid content in the liver. Finally, we found that the expression of several genes involved in MUFA and PUFA synthesis (Scd1, Fads1, Fads2, Elovl2, and Elovl5) was dysregulated in mice inoculated with an aged microbiota. In conclusion, our data suggest that changes in gut microbiota that are associated with aging can impact brain and liver lipid metabolisms. Lipid changes induced by an aged microbiota recapitulate some features of aging, thus pointing out the potential role of microbiota alterations in the age-related degradation of the health status.}, }
@article {pmid31993353, year = {2019}, author = {Xi, D and Michail, S}, title = {Fecal microbiota transplantation in children does not significantly alter body mass index.}, journal = {Translational pediatrics}, volume = {8}, number = {5}, pages = {398-401}, pmid = {31993353}, issn = {2224-4344}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is nowadays a promising therapy for Clostridium difficile infection (CDI) and a potential treatment for ulcerative colitis. However, it is still unclear whether the changes in intestinal microbiome will affect energy homeostasis or metabolism. This brings an intriguing question whether FMT from healthy donors affects recipient's body mass index (BMI).<br><br>METHODS: In our randomized placebo-controlled study children patients with CDI or ulcerative colitis were randomly divided into control and FMT groups. The change of post-FMT BMI percentile at 1, 3, 6, 12 months was calculated. The age range of CDI cohort was 1 to 17 years, while the range was 8 to 21 years for ulcerative colitis cohort.<br><br>RESULTS: We found that the BMI percentile was insignificantly changed by &#x2012;0.7%, &#x2012;1.8%, 1.3%, 4.6% in CDI, while by 3.6%, &#x2012;3.3%, 3.7%, 7.1% in ulcerative colitis at 1, 3, 6, 12 months after FMT ("&#x2012;" means decrease).<br><br>CONCLUSIONS: We concluded that FMT from healthy donors does not significantly alter BMI in children with CDI and ulcerative colitis over 12 months.}, }
@article {pmid31992630, year = {2020}, author = {Oliphant, K and Cochrane, K and Schroeter, K and Daigneault, MC and Yen, S and Verdu, EF and Allen-Vercoe, E}, title = {Effects of Antibiotic Pretreatment of an Ulcerative Colitis-Derived Fecal Microbial Community on the Integration of Therapeutic Bacteria In Vitro.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {31992630}, issn = {2379-5077}, abstract = {Fecal microbiota transplantation (FMT) is a proposedly useful strategy for the treatment of gastrointestinal (GI) disorders through remediation of the patient gut microbiota. However, its therapeutic success has been variable, necessitating research to uncover mechanisms that improve patient response. Antibiotic pretreatment has been proposed as one method to enhance the success rate by increasing niche availability for introduced species. Several limitations hinder exploring this hypothesis in clinical studies, such as deleterious side effects and the development of antimicrobial resistance in patients. Thus, the purpose of this study was to evaluate the use of an in vitro, bioreactor-based, colonic ecosystem model as a form of preclinical testing by determining how pretreatment with the antibiotic rifaximin influenced engraftment of bacterial strains sourced from a healthy donor into an ulcerative colitis-derived defined microbial community. Distinct species integrated under the pretreated and untreated conditions, with the relative rifaximin resistance of the microbial strains being an important influencer. However, both conditions resulted in the integration of taxa from Clostridium clusters IV and XIVa, a concomitant reduction of Proteobacteria, and similar decreases in metabolites associated with poor health status. Our results agree with the findings of similar research in the clinic by others, which observed no difference in primary patient outcomes whether or not patients were given rifaximin prior to FMT. We therefore conclude that our model is useful for screening for antibiotics that could improve efficacy of FMT when used as a pretreatment.IMPORTANCE Patients with gastrointestinal disorders often exhibit derangements in their gut microbiota, which can exacerbate their symptoms. Replenishing these ecosystems with beneficial bacteria through fecal microbiota transplantation is thus a proposedly useful therapeutic; however, clinical success has varied, necessitating research into strategies to improve outcomes. Antibiotic pretreatment has been suggested as one such approach, but concerns over harmful side effects have hindered testing this hypothesis clinically. Here, we evaluate the use of bioreactors supporting defined microbial communities derived from human fecal samples as models of the colonic microbiota in determining the effectiveness of antibiotic pretreatment. We found that relative antimicrobial resistance was a key determinant of successful microbial engraftment with rifaximin (broad-spectrum antibiotic) pretreatment, despite careful timing of the application of the therapeutic agents, resulting in distinct species profiles from those of the control but with similar overall outcomes. Our model had results comparable to the clinical findings and thus can be used to screen for useful antibiotics.}, }
@article {pmid31991615, year = {2020}, author = {Feehan, A and Garcia-Diaz, J}, title = {Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, pmid = {31991615}, issn = {2076-2607}, abstract = {Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected to evolve resistance to most new compounds as well. Multidrug resistant organisms (MDROs) that cause infections increase morbidity, mortality, and readmissions as compared with susceptible organisms. Consequently, many research and development pipelines are focused on non-antibiotic strategies, including fecal microbiota transplantation (FMT), probiotics and prebiotics, and a range of therapies in between. Studies reviewed here focus on efforts to directly treat or prevent MDRO infections or colonization. The studies were collected through clinicaltrials.gov, PubMed, and the International Conference on the Harmonisation Good Clinical Practice website (ichgcp.net). While the gold standard of clinical research is randomized controlled trials (RCTs), several pilot studies are included because the field is so young. Although a vast preclinical body of research has led to studies in humans, animal and in vitro studies are not within the scope of this review. This narrative review discusses microbiome-modifying therapies targeting MDROs in the gut and includes current results, ongoing clinical trials, companies with therapies in the pipeline specifically for MDROs, and commentary on clinical implementation and challenges.}, }
@article {pmid31991477, year = {2020}, author = {Fitzgibbon, G and Mills, KHG}, title = {The microbiota and immune-mediated diseases: Opportunities for therapeutic intervention.}, journal = {European journal of immunology}, volume = {50}, number = {3}, pages = {326-337}, doi = {10.1002/eji.201948322}, pmid = {31991477}, issn = {1521-4141}, support = {16/IA/4468/SFI_/Science Foundation Ireland/Ireland ; 12/RI/2340/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {Animals ; Humans ; Microbiota/*immunology ; }, abstract = {A multitude of diverse microorganisms, termed the microbiota, reside in the gut, respiratory tract, skin, and genital tract of humans and other animals. Recent advances in metagenomic sequencing and bioinformatics have enabled detailed characterization of these vital microbial communities. Studies in animal models have uncovered vital previously unrecognized roles for the microbiota in normal function of the immune responses, and when perturbed, in the pathogenesis of diseases of the gastrointestinal tract and lungs, but also at distant sites in the body including the brain. The composition of gut and respiratory microbiota can influence systemic inflammatory responses that mediate asthma, allergy, inflammatory bowel disease, obesity-related diseases, and neurodevelopmental or neurodegenerative conditions. Experiments in mouse models as well as emerging clinical studies have revealed that therapeutic manipulation of the microbiota, using fecal microbiota transplantation, probiotics, or engineered probiotics represent effective nontoxic approaches for the treatment or prevention of Clostridium difficile infection, allergy, and autoimmune diseases and may enhance the efficacy of certain cancer immunotherapeutics. This review discusses how commensal bacteria can influence immune responses that mediate a range of human diseases and how the microbiota are being targeted to treat these diseases, especially those resistant to pharmacological therapies.}, }
@article {pmid31991379, year = {2020}, author = {Hakoda, K and Yoshimitsu, M and Miguchi, M and Kohashi, T and Egi, H and Ohdan, H and Hirabayashi, N}, title = {Characteristic findings of appendicular endometriosis treated with single incision laparoscopic ileocolectomy: Case report.}, journal = {International journal of surgery case reports}, volume = {67}, number = {}, pages = {9-12}, pmid = {31991379}, issn = {2210-2612}, abstract = {INTRODUCTION: We report the case of characteristic findings of appendicular endometriosis that presented as a submucosal tumor in the cecum without any abdominal symptoms treated with single-incision laparoscopic ileocolectomy.<br><br>PRESENTATION OF CASE: The patient was a 51-year-old woman (body mass index: 21.5) who underwent an examination to investigate the cause of a positive fecal occult blood test. Her laboratory test results were normal, without anemia or tumor marker elevation. Colonoscopy revealed a submucosal tumor in the cecum. Enhanced computed tomography (CT), fluorodeoxyglucose-positron emission tomography-CT and magnetic resonance imaging failed to produce a clear diagnosis. Given the malignant potentiality of the tumor, ileocolectomy was considered potentially necessary, but she wished for minimally invasive surgery. She ultimately underwent ileocolectomy and lymphadenectomy with single-incision laparoscopic surgery. A pathological examination revealed the lesion to be appendicular endometriosis, and 14 lymph nodes with no malignancy were resected.<br><br>CONCLUSION: Appendicular endometriosis can present as a submucosal tumor in the cecum without any abdominal symptoms. Appendicular endometriosis should be considered in the differential diagnosis of ileocecal submucosal tumor. Single-incision laparoscopic ileocolectomy was useful procedure for cecum tumor resection.}, }
@article {pmid31989644, year = {2020}, author = {Osei Sekyere, J and Maningi, NE and Fourie, PB}, title = {Mycobacterium tuberculosis, antimicrobials, immunity, and lung-gut microbiota crosstalk: current updates and emerging advances.}, journal = {Annals of the New York Academy of Sciences}, volume = {1467}, number = {1}, pages = {21-47}, doi = {10.1111/nyas.14300}, pmid = {31989644}, issn = {1749-6632}, mesh = {Animals ; Anti-Infective Agents/*therapeutic use ; Gastrointestinal Microbiome/*immunology ; Humans ; Lung/*microbiology ; Mice ; *Mycobacterium tuberculosis ; Tuberculosis/*drug therapy/microbiology ; }, abstract = {Increasingly, gut microbiota distortions are being implicated in the pathogenesis of several infectious and noninfectious diseases. Specifically, in the absence of an eubiotic microbiota, mice are more prone to colonization and infection by Mycobacterium tuberculosis (Mtb). In this qualitative analysis, the following were observed: (1) antimicrobials cause long-term gut microbiota perturbations; (2) Mtb causes limited and transient disturbances to the lung-gut microbiota; (3) pathogens (e.g., Helicobacter hepaticus) affect microbiota integrity and reduce resistance to Mtb; (4) dysbiosis depletes bacterial species regulating proper immune functioning, reducing resistance to Mtb; (5) dysregulated immune cells fail to express important pathogen-recognition receptors (e.g., macrophage-inducible C-type lectin; MINCLE) and Mtb-killing cytokines (e.g., IFN-γ, TNF-α, and IL-17), with hampered phagocytic capability; (6) autophagy is central to the immune system's clearance of Mtb, control of inflammation, and immunity-microbiome balance; (7) microbiota-produced short-chain fatty acids, which are reduced by dysbiosis, affect immune cells and increase Mtb proliferation; (8) commensal species (e.g., Lactobacillus plantarum) and microbiota metabolites (e.g., indole propionic acid) reduce tuberculosis progression; and (9) fecal transplants mostly restored eubiosis, increased immune resistance to Mtb, restricted dissemination of Mtb, and reduced tuberculosis-associated organ pathologies. Overuse of antimicrobials, as shown in mice, is a risk factor for reactivating latent or treated tuberculosis.}, }
@article {pmid31986084, year = {2020}, author = {Schwabkey, ZI and Jenq, RR}, title = {Microbiome Anomalies in Allogeneic Hematopoietic Cell Transplantation.}, journal = {Annual review of medicine}, volume = {71}, number = {}, pages = {137-148}, pmid = {31986084}, issn = {1545-326X}, support = {R01 HL124112/HL/NHLBI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*microbiology ; Biodiversity ; Clostridium Infections/*microbiology ; Dysbiosis/etiology/*microbiology/therapy ; Febrile Neutropenia/drug therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Graft vs Host Disease/*microbiology ; Hematopoietic Stem Cell Transplantation/adverse effects/*methods ; Humans ; Microbiota/physiology ; Prebiotics ; Probiotics ; Respiratory Tract Infections/*microbiology ; Transplantation, Homologous ; }, abstract = {The microbiome is an integrated part of the human body that can modulate a variety of disease processes and affect prognosis, treatment response, complications, and outcomes. The importance of allogeneic hematopoietic cell transplantation in cancer treatment has resulted in extensive investigations on the interaction between the microbiome and this treatment modality. These investigations are beginning to lead to clinical trials of microbiome-targeted interventions. Here we review some of these discoveries and describe strategies being investigated to manipulate the microbiome for favorable outcomes, such as the proper selection and timing of antibiotics, type of diet and route of administration, probiotics, prebiotics, and fecal microbiota transplantation.}, }
@article {pmid31982069, year = {2020}, author = {Allegretti, JR and Mullish, BH}, title = {Faecal microbiota transplantations and urinary tract infections - Authors' reply.}, journal = {Lancet (London, England)}, volume = {395}, number = {10220}, pages = {271}, doi = {10.1016/S0140-6736(19)32978-2}, pmid = {31982069}, issn = {1474-547X}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Urinary Tract Infections ; }, }
@article {pmid31982066, year = {2020}, author = {Lagier, JC and Raoult, D}, title = {Faecal microbiota transplantations and urinary tract infections.}, journal = {Lancet (London, England)}, volume = {395}, number = {10220}, pages = {270-271}, doi = {10.1016/S0140-6736(19)32992-7}, pmid = {31982066}, issn = {1474-547X}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Humans ; *Urinary Tract Infections ; }, }
@article {pmid31980603, year = {2020}, author = {Yu, M and Malik Tyagi, A and Li, JY and Adams, J and Denning, TL and Weitzmann, MN and Jones, RM and Pacifici, R}, title = {PTH induces bone loss via microbial-dependent expansion of intestinal TNF[+] T cells and Th17 cells.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {468}, pmid = {31980603}, issn = {2041-1723}, support = {R01 DK112946/DK/NIDDK NIH HHS/United States ; S10 RR028009/RR/NCRR NIH HHS/United States ; U54 AG062334/AG/NIA NIH HHS/United States ; R01 DK124821/DK/NIDDK NIH HHS/United States ; R01 DK119229/DK/NIDDK NIH HHS/United States ; R01 DK108842/DK/NIDDK NIH HHS/United States ; R01 AR068157/AR/NIAMS NIH HHS/United States ; R01 AR070091/AR/NIAMS NIH HHS/United States ; I01 BX000105/BX/BLRD VA/United States ; R01 DK098391/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Germ-Free Life ; Gram-Positive Endospore-Forming Rods/immunology ; Hyperparathyroidism, Primary/complications/immunology/microbiology ; Intestines/immunology/microbiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Osteoporosis/*etiology/immunology/microbiology ; Parathyroid Hormone/*immunology ; T-Lymphocyte Subsets/*immunology ; Th17 Cells/*immunology ; Tumor Necrosis Factor-alpha/immunology ; }, abstract = {Bone loss is a frequent but not universal complication of hyperparathyroidism. Using antibiotic-treated or germ-free mice, we show that parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched by the Th17 cell-inducing taxa segmented filamentous bacteria (SFB). SFB[+] microbiota enabled PTH to expand intestinal TNF[+] T and Th17 cells and increase their S1P-receptor-1 mediated egress from the intestine and recruitment to the bone marrow (BM) that causes bone loss. CXCR3-mediated TNF[+] T cell homing to the BM upregulated the Th17 chemoattractant CCL20, which recruited Th17 cells to the BM. This study reveals mechanisms for microbiota-mediated gut-bone crosstalk in mice models of hyperparathyroidism that may help predict its clinical course. Targeting the gut microbiota or T cell migration may represent therapeutic strategies for hyperparathyroidism.}, }
@article {pmid31978342, year = {2020}, author = {Walter, J and Armet, AM and Finlay, BB and Shanahan, F}, title = {Establishing or Exaggerating Causality for the Gut Microbiome: Lessons from Human Microbiota-Associated Rodents.}, journal = {Cell}, volume = {180}, number = {2}, pages = {221-232}, doi = {10.1016/j.cell.2019.12.025}, pmid = {31978342}, issn = {1097-4172}, support = {//CIHR/Canada ; }, mesh = {Animals ; Disease/etiology ; Dysbiosis/*microbiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Mice ; Microbiota/physiology ; Models, Animal ; Rats ; Rodentia/*microbiology ; }, abstract = {Human diseases are increasingly linked with an altered or "dysbiotic" gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer of pathological phenotypes to recipient animals, and many extrapolated the findings to make causal inferences to human diseases. We posit that this exceedingly high rate of inter-species transferable pathologies is implausible and overstates the role of the gut microbiome in human disease. We advocate for a more rigorous and critical approach for inferring causality to avoid false concepts and prevent unrealistic expectations that may undermine the credibility of microbiome science and delay its translation.}, }
@article {pmid31976518, year = {2021}, author = {Stoma, I and Littmann, ER and Peled, JU and Giralt, S and van den Brink, MRM and Pamer, EG and Taur, Y}, title = {Compositional Flux Within the Intestinal Microbiota and Risk for Bloodstream Infection With Gram-negative Bacteria.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {73}, number = {11}, pages = {e4627-e4635}, pmid = {31976518}, issn = {1537-6591}, support = {U01 Al124275/NH/NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; //National Institute of Allergy and Infectious Diseases/ ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; P30 CA008748/NH/NIH HHS/United States ; }, mesh = {*Bacteremia/microbiology ; *Gastrointestinal Microbiome ; Gram-Negative Bacteria ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Retrospective Studies ; *Sepsis/complications ; }, abstract = {BACKGROUND: Gram-negative bloodstream infections (BSIs) represent a significant complication facing allogeneic hematopoietic cell transplant (allo-HCT) recipients, as a result of intestinal translocation during neutropenia. In this study we sought to better understand how the composition of the intestinal microbiota is connected to risk of gram-negative BSIs, expanding on our prior work in these patients.<br><br>METHODS: Fecal specimens were collected from recipients of allo-HCT and analyzed using 16S ribosomal RNA gene sequencing. Samples and clinical data extending from the pretransplant conditioning period through stem cell engraftment were used in the analysis. Intestinal domination (relative abundance &#x2265;&#x2009;30%) by gram-negative bacteria was used as predictor of gram-negative BSI using Cox proportional hazards modeling. Further analysis of microbiota composition was performed at the genus level.<br><br>RESULTS: Seven hundred eight allo-HCT subjects were studied (7.5% developed gram-negative infection), with 4768 fecal samples for analysis. Gram-negative intestinal domination was associated with subsequent BSI, which was observed overall and individually at the genus level: Escherichia, Klebsiella, Enterobacter, Pseudomonas, and Stenotrophomonas. Fluoroquinolone prophylaxis was associated with decreased BSI and intestinal colonization by gram-negative microbes. In fluoroquinolone-prophylaxed patients, Escherichia coli was more frequently observed as breakthrough, both in terms of intestinal colonization and BSIs, compared with nonprophylaxed patients. Initial colonization by members of Ruminococcaceae and Bacteroidetes were associated with protection against gram-negative BSI.<br><br>CONCLUSIONS: Gram-negative intestinal colonization is highly predictive of BSI in the setting of allo-HCT. Fluoroquinolones appear to reduce these infections by influencing gut colonization.}, }
@article {pmid31976311, year = {2019}, author = {Garza-González, E and Mendoza-Olazarán, S and Morfin-Otero, R and Ramírez-Fontes, A and Rodríguez-Zulueta, P and Flores-Treviño, S and Bocanegra-Ibarias, P and Maldonado-Garza, H and Camacho-Ortiz, A}, title = {Intestinal Microbiome Changes in Fecal Microbiota Transplant (FMT) vs. FMT Enriched with Lactobacillus in the Treatment of Recurrent Clostridioides difficile Infection.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {2019}, number = {}, pages = {4549298}, pmid = {31976311}, issn = {2291-2797}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Clostridioides difficile ; Double-Blind Method ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; *Lactobacillus ; Male ; Middle Aged ; Pilot Projects ; RNA, Ribosomal, 16S ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {AIM: In this study, we conducted a comparative study to explore the differences in therapeutic efficacy and intestinal microbiome of fecal microbiota transplant (FMT) vs. FMT in addition with Lactobacillus (FMT-L) for treatment of recurrent Clostridioides difficile infection (R-CDI).<br><br>METHODS: We designed a double-blinded randomized comparative two-arm pilot multicenter study to assess the efficacy and impact in the intestinal microbiome of standard capsules of FMT vs. FMT-L enriched with 3 species of Lactobacillus for patients with R-CDI. A 90-day follow-up of 21 patients was performed, starting at the beginning of the study. From the selected patients, fecal samples were obtained at days 0, 3, 7, and 28 after treatment. Fecal samples and FMT were analyzed by 16S rRNA sequencing.<br><br>RESULTS: We included 21 patients (13 in the FMT group and 8 in the FMT-L group). Overall, both groups had a reduction in bowel movements per day, from 8.6 to 3.2 in the first 48&#x2009;h (62.7% reduction, p=0.001). No severe adverse reactions or recurrences were recorded. Firmicutes were the most abundant phylum in donors. A low relative abundance of Proteobacteria was detected and mostly found in patients even at higher proportions than the donor. The donor's pool also had relatively few Bacteroidetes, and some patients showed a higher abundance of this phylum. Based on the ANOSIM R values, there is a significant difference between the microbial communities of basal samples and samples collected on day 7 (p=0.045) and at day 28 (0.041).<br><br>CONCLUSION: Fecal microbiota transplant by capsules was clinically and genomically similar between traditional FMT and enriched FMT with Lactobacillus spp. Restoration of bacterial diversity and resolution of dysbiosis at days 7 and 28 were observed. Patients with a first episode of recurrence treated with FMT had an excellent response without severe adverse events; FMT should be considered as an early treatment during R-CDI.}, }
@article {pmid31975529, year = {2020}, author = {Groves, HE and Allen, UD}, title = {Winning with poo? Fecal microbiome transplantation as an emerging strategy for the management of recurrent Clostridioides difficile infection in children.}, journal = {Pediatric transplantation}, volume = {24}, number = {1}, pages = {e13651}, doi = {10.1111/petr.13651}, pmid = {31975529}, issn = {1399-3046}, mesh = {Child, Preschool ; *Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; *Heart Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid31974041, year = {2020}, author = {Lou, JM and Ren, ZG and Li, A and Rao, BC and Yu, ZJ}, title = {Fecal microbiota transplantation has therapeutic effects on chronic hepatits B patients via altering composition of gut microbiota.}, journal = {Hepatobiliary &amp; pancreatic diseases international : HBPD INT}, volume = {19}, number = {5}, pages = {486-487}, doi = {10.1016/j.hbpd.2019.12.008}, pmid = {31974041}, issn = {1499-3872}, mesh = {Antiviral Agents/therapeutic use ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Hepatitis B, Chronic/drug therapy/*therapy ; Humans ; }, }
@article {pmid31973773, year = {2020}, author = {Stalder, T and Kapel, N and Diaz, S and Grenouillet, F and Koch, S and Limat, S and Daval, F and Vuitton, L and Nerich, V}, title = {A systematic review of economic evaluation in fecal microbiota transplantation.}, journal = {Infection control and hospital epidemiology}, volume = {41}, number = {4}, pages = {458-466}, doi = {10.1017/ice.2019.371}, pmid = {31973773}, issn = {1559-6834}, mesh = {Anti-Bacterial Agents/economics/therapeutic use ; Clostridioides difficile ; Clostridium Infections/drug therapy/*economics/*therapy ; Cost-Benefit Analysis ; Fecal Microbiota Transplantation/*economics ; Humans ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapy in recurrent Clostridium difficile infection (rCDI). It is only recommended for this indication by European and American guidelines. Other indications of FMT are being studied, such as inflammatory bowel disease (IBD), and they have shown promising results.<br><br>OBJECTIVES: To identify and review published FMT-related economic evaluations (EEs) to assess their quality and the economic impact of FMT in the treatment of these diseases.<br><br>DATA SOURCES: The systematic literature research was conducted in both PubMed and Cochrane to identify EEs published before July 1, 2019.<br><br>STUDY ELIGIBILITY CRITERIA: Articles were included if they concerned FMT (whatever the disease and its line of treatment), if they reported full or partial EEs, and if they were written in English. Articles were excluded if they did not concern FMT; if they did not report an EE; or if they were a systematic review, editorial, comment, letter to the editor, practice point, or poster.<br><br>METHODS: A measurement tool, AMSTAR, was used to optimize the quality of this systematic review. Based on the CHEERS checklist, data were identified and extracted from articles. The quality of each EE was assessed using the Drummond checklist.<br><br>RESULTS: Overall, 9 EEs were included: all EEs were full evaluations and 8 were cost-utility analyses (CUAs). All EEs had a Drummond score &#x2265; 7, which indicated high quality. All CUAs related to rCDI and IBD concluded that FMT was cost-effective compared with other reference treatments, at a threshold &#x2264;$50,000/QALY. One EE about initial CDI showed that FMT was dominated by metronidazole.<br><br>CONCLUSIONS: Despite a limited number of EEs, FMT seems to be a promising and cost-effective treatment for rCDI. More EE studies on other diseases like IBD are necessary to address FMT efficiency for new indications. Therefore, our systematic review provides a framework for healthcare decision making.}, }
@article {pmid31973214, year = {2020}, author = {Safari, Z and Bruneau, A and Monnoye, M and Mariadassou, M and Philippe, C and Zatloukal, K and Gérard, P}, title = {Murine Genetic Background Overcomes Gut Microbiota Changes to Explain Metabolic Response to High-Fat Diet.}, journal = {Nutrients}, volume = {12}, number = {2}, pages = {}, pmid = {31973214}, issn = {2072-6643}, support = {W 1226/FWF_/Austrian Science Fund FWF/Austria ; W1226//FWF/ ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Diet, High-Fat/*adverse effects ; Gastrointestinal Microbiome/*genetics ; *Genetic Background ; Genetic Predisposition to Disease/genetics ; Metabolic Diseases/etiology/*genetics/*microbiology ; Mice ; Mice, Inbred C57BL ; }, abstract = {Interactions of diet, gut microbiota, and host genetics play essential roles in the development of metabolic diseases. A/J and C57BL/6J (C57) are two mouse strains known to display different susceptibilities to metabolic disorders. In this context, we analyzed gut microbiota composition in A/J and C57 mice, and assessed its responses to high-fat diet (HFD) and antibiotic (AB) treatment. We also exchanged the gut microbiota between the two strains following AB treatment to evaluate its impact on the metabolism. We showed that A/J and C57 mice have different microbiome structure and composition at baseline. Moreover, A/J and C57 microbiomes responded differently to HFD and AB treatments. Exchange of the gut microbiota between the two strains was successful as recipients' microbiota resembled donor-strain microbiota. Seven weeks after inoculation, the differences between recipients persisted and were still closer from the donor-strain microbiota. Despite effective microbiota transplants, the response to HFD was not markedly modified in C57 and A/J mice. Particularly, body weight gain and glucose intolerance in response to HFD remained different in the two mouse strains whatever the changes in microbiome composition. This indicated that genetic background has a much stronger impact on metabolic responses to HFD than gut microbiome composition.}, }
@article {pmid31972620, year = {2020}, author = {Ekekezie, C and Perler, BK and Wexler, A and Duff, C and Lillis, CJ and Kelly, CR}, title = {Understanding the Scope of Do-It-Yourself Fecal Microbiota Transplant.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {4}, pages = {603-607}, pmid = {31972620}, issn = {1572-0241}, support = {DP5 OD026420/OD/NIH HHS/United States ; }, mesh = {Adult ; Clostridioides difficile ; Clostridium Infections/*therapy ; Cross-Sectional Studies ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; *Self Care ; Social Media ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) has emerged as an effective treatment option for Clostridioides difficile infection (CDI) and is considered an investigational therapy for a number of other diseases. Social media has facilitated widespread exposure of the public to the gut microbiome and FMT, ultimately acting as a catalyst for the Do-It-Yourself (DIY)-FMT movement. The aims of this study were to identify factors that influenced willingness to pursue DIY-FMT including common indications, screening processes, sample preparation, and self-reported efficacy and safety outcomes.<br><br>METHODS: A twenty-five-point cross-sectional survey was posted online through the websites and social media pages of the Peggy Lillis Foundation, The Fecal Transplant Foundation, and The Power of Poop. Responses were cataloged through the Research Electronic Data Capture tool, and descriptive analyses were performed.<br><br>RESULTS: Eighty-four respondents completed the survey between January 2018 and February 2019. The majority were female (71%) and white (92%). Most (80%) reported performing FMT on themselves; 87% used Internet resources to assist in the process, and 92% knew their stool donor. Inflammatory bowel disease (35%) and irritable bowel syndrome (29%) were the 2 most common conditions that respondents attempted to treat. Only 12% reported adverse events, whereas 82% reported improvement in their condition.<br><br>DISCUSSION: DIY-FMT is being used for many indications, including those for which there is little evidence. There was a high self-reported success rate among respondents with few adverse events. There is a need for increased awareness around DIY-FMT and research around this phenomenon, which may impact public health.}, }
@article {pmid31968211, year = {2020}, author = {Antushevich, H}, title = {Fecal microbiota transplantation in disease therapy.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {503}, number = {}, pages = {90-98}, doi = {10.1016/j.cca.2019.12.010}, pmid = {31968211}, issn = {1873-3492}, mesh = {Fecal Microbiota Transplantation/adverse effects/*methods ; Gastrointestinal Diseases/therapy ; Humans ; Metabolic Syndrome/therapy ; Neoplasms/therapy ; Nervous System Diseases/therapy ; Parkinson Disease/therapy ; Therapeutics/adverse effects/*methods ; }, abstract = {Fecal microbiota transplantation (FMT) is the introduction (transplantation) of gut microbiota obtained from the faeces of a healthy donor into the patient's gastrointestinal tract. Most often, such therapy is used the treatment of gastrointestinal diseases caused by the activity of pathogenic or conditionally pathogenic microorganisms, however, recently an increasing number of studies have reported the use of fecal microbiota transplantation for the treatment of diseases such as metabolic syndrome, diabetes, cancer and Parkinson's disease. This review article presents the results of studies concerning the impact of FMT on weight gain, immunological response and the treatment of neurological and gastrointestinal diseases and cancer. The procedure of fecal microbiota transplantation and possible side effects that may appear in FMT recipients are also described.}, }
@article {pmid31964766, year = {2020}, author = {Bircher, L and Schwab, C and Geirnaert, A and Greppi, A and Lacroix, C}, title = {Planktonic and Sessile Artificial Colonic Microbiota Harbor Distinct Composition and Reestablish Differently upon Frozen and Freeze-Dried Long-Term Storage.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {31964766}, issn = {2379-5077}, abstract = {Biofilm-associated, sessile communities represent the major bacterial lifestyle, whereas planktonic cells mainly appear during initial colonization of new surfaces. Previous research, mainly performed with pathogens, demonstrated increased environmental stress tolerance of biofilm-growing compared to planktonic bacteria. The lifestyle-specific stress response of colonic microbiota, both natural and fermentation produced, has not been addressed before. Planktonic and sessile "artificial" colonic microbiota delivered by PolyFermS continuous fermentation models can provide a controllable and reproducible alternative to fecal transplantation in treating gastrointestinal disorders. We therefore characterized planktonic and sessile microbiota produced in two PolyFermS models inoculated with immobilized fecal microbiota and comparatively tested their levels of tolerance of frozen storage (-80°C) and freeze-dried storage (4°C) for 9 months to mimic preservation strategies for therapeutic applications. Sessile microbiota harbored next to shared taxa a unique community distinguishable from planktonic microbiota. Synergistetes and Proteobacteria were highly represented in sessile microbiota, while Firmicutes were more abundant in planktonic microbiota. The community structure and metabolic activity of both microbiota, monitored during standardized reactivation batch fermentations, were better preserved after frozen storage than dried storage, indicated by higher Bray-Curtis similarity and enhanced recovery of metabolite production. For both lifestyles, reestablishment of Bacteroidaceae was impaired after frozen and dried storage along with reduced propionate formation. In contrast, butyrate production was maintained after reactivation despite compositional rearrangements within the butyrate-producing community. Unexpectedly, the rate of recovery of metabolite production was lower after preservation of sessile than planktonic microbiota. We speculate that higher functional dependencies between microbes might have led to the lower stress tolerance of sessile than planktonic microbiota.IMPORTANCE Fecal microbiota transplantation has been successfully applied in the treatment of recurrent Clostridium difficile infection and has been suggested as an alternative therapy for other intestinal disorders such as inflammatory bowel disease or metabolic syndrome. "Artificial" colonic microbiota delivered by PolyFermS continuous fermentation models can provide a controllable and reproducible alternative to fecal transplantation, but effective preservation strategies must be developed. In this study, we systematically investigated the response of sessile and planktonic artificial colonic microbiota to cryopreservation and lyophilization. We suggest that functional redundancy is an important factor in providing functional stability with respect to exposure to stress during processing and storage. Functional redundancy in compositionally reduced microbial systems may be considered when designing microbial products for therapy.}, }
@article {pmid31963653, year = {2020}, author = {Xu, R and Wan, J and Lin, C and Su, Y}, title = {Effects of Early Intervention with Antibiotics and Maternal Fecal Microbiota on Transcriptomic Profiling Ileal Mucusa in Neonatal Pigs.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {1}, pages = {}, pmid = {31963653}, issn = {2079-6382}, support = {31572414 and 31872362//National Natural Science Foundation of China/ ; }, abstract = {This study aimed to investigate the effects of early intervention with antibiotics and maternal fecal microbiota on ileal morphology and barrier function, and transcriptomic profiling in neonatal piglets. Piglets in the amoxicillin (AM), fecal microbiota transplantation (FMT), and control (CO) groups were orally administrated with amoxicillin solution (6.94 mg/mL), maternal fecal microbiota suspension [>10[9] colony forming unit (CFU)/mL], and physiological saline, respectively. Compared with the CO group, early intervention with AM or FMT significantly decreased ileal crypt depth on day 7 and altered gene expression profiles in ileum on days 7 and 21, and especially promoted the expression of chemokines (CCL5, CXCL9, and CXCL11) involved in the toll-like receptor signaling pathway on day 21. FMT changed major immune activities from B cell immunity on day 7 to T cell immunity on day 21 in the ileum. On the other hand, both AM and FMT predominantly downregulated the gene expression of toll-like receptor 4 (TLR4). In summary, both early interventions modulated intestinal barrier function and immune system in the ileum with a low impact on ileal morphology and development.}, }
@article {pmid31961792, year = {2020}, author = {Barcán, L and Ducatenzeiler, L and Bangher, MDC and Barcelona, L and Cornistein, W and Daciuk, L and De Paula, J and Desse, J and Dictar, M and Fernández-Canigia, L and Nacinovich, F and Scapellato, P and Martínez, JV and ,  and ,  and ,  and ,  and ,  and ,  and ,  and ,  and ,  and , }, title = {[Intersociety guidelines for diagnosis, treatment and prevention of Clostridioides difficile infections].}, journal = {Medicina}, volume = {80 Suppl 1}, number = {}, pages = {1-32}, pmid = {31961792}, issn = {1669-9106}, mesh = {Argentina ; Clinical Laboratory Techniques ; Clostridium Infections/*diagnosis/prevention &amp; control/*therapy ; Humans ; Risk Factors ; Societies, Medical ; }, abstract = {Clostridioides difficile infections (CDI) are among the leading causes of health care-associated infections. The epidemiology of CDI has undergone major changes in the last decade, showing an increase in incidence, severity, and rate of relapse. These guidelines were developed by specialists from four scientific societies: Sociedad Argentina de Infectología (SADI), Sociedad Argentina de Gastroenterología (SAGE), Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas (SADEBAC) and Asociación de Enfermeras en Control de Infecciones (ADECI). The objective of these intersociety guidelines is to provide national recommendations on CDI diagnosis, treatment and prevention. The methodology used involved the systematic review of the bibliography available up to December 2018, which was performed by six groups formed ad hoc: Epidemiology, Diagnosis, Treatment, Fecal Microbiota Transplantation, Special Populations, and Infection Control. The conclusions were presented and discussed in meetings held by each individual group and plenary meetings. In this document, updated diagnosis algorithms, therapeutic options (including fecal microbiota transplant) for immunocompetent and immunocompromised patients are presented, as well as strategies for the control of C. difficile infection.}, }
@article {pmid31958930, year = {2020}, author = {Chen, QY and Tian, HL and Yang, B and Lin, ZL and Zhao, D and Ma, CL and Chen, X and Jiang, J and Qin, HL and Li, N}, title = {[Diagnosis and treatment of superior mesenteric artery compression syndrome secondary to chronic constipation (Lee's triad syndrome)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {1}, pages = {44-50}, doi = {10.3760/cma.j.issn.1671-0274.2020.01.008}, pmid = {31958930}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {Chronic Disease ; Cohort Studies ; Constipation/*complications ; Enteral Nutrition ; Fecal Microbiota Transplantation ; Humans ; Knee-Chest Position ; Mesenteric Artery, Superior/diagnostic imaging ; Quality of Life ; Superior Mesenteric Artery Syndrome/*diagnosis/diagnostic imaging/etiology/*therapy ; Syndrome ; Treatment Outcome ; }, abstract = {Objective: To summarize the experience of diagnosis and treatment of superior mesenteric artery compression syndrome (SMACS) secondary to chronic constipation according to the concept of Lee's triad syndrome. Methods: The concept of Lee's triad syndrome: (1) clinical symptoms: triad of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, difficulty in eating); (2) anatomical manifestations: with triple anatomy anomaly of transverse colon sagging, elevated spleen flexure, and mesentery arterial compression; (3) treatment: with triple treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation. A descriptive cohort study was performed. According to Lee's triad syndrome criteria, clinical data of 78 patients with superior mesenteric artery compression syndrome secondary to chronic constipation in the Tenth People's Hospital of Tongji University and General Hospital of Eastern Theater Command from June 2004 to November 2018 were prospectively collected, including basic information, symptoms and signs, imaging findings, nutritional indicators, gastrointestinal quality of life index (GIQLI) and Wexner defecation score. The above parameters based on Lee's triad syndrome criteria were followed up and recorded at 1, 3, 6, 12 months after comprehensive treatment. Results: All the patients had Lee's triple symptoms of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, eating difficulties), and triple anatomy anomaly of transverse colon sagging, elevated spleen curvature, and mesentery arterial compression before treatment. After triple treatment of enteral nutrition support, chest-knee posture, and fecal microbiota transplantation, 69 (88.5%) patients had a significant improvement of symptoms, and 9 patients had no significant improvement of symptoms and then eventually received surgery. The 69 cases without operation received follow-up for 12 months. All the patients eventually returned to normal eating, and upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression disappeared. After 1 month, the constipation-related indexes were improved. After 12 months, the number of autonomous defecation per week increased from 1.0±0.8 to 5.0±1.6 (P<0.001). The GIQLI score increased from 52.7±8.5 to 93.2±7.5 (P<0.001), and the Wexner score decreased from 19.1±2.5 to 6.2±2.1 (P<0.001). After 1 month, nutritional indexes were improved gradually. After 12 months, the BMI increased from (17.9±1.8) kg/m(2) to (21.0±1.3) kg/m(2), total protein increased from (65.2±5.7) g/L to (68.3±4.2) g/L, albumin increased from (32.1±5.1) g/L to (40.4±3.0) g/L, prealbumin increased from (163.2±53.7) mg/L to (259.1±45.6) mg/L, fibrinogen increased from (1.9±0.5) g/L to (2.4±0.5) g/L, whose differences were statistically significant (all P<0.001). Upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression were relieved. The angle between superior mesenteric artery and abdominal aorta increased from (17.4±3.8)° to (37.8±5.8)° (t=-22.26, P<0.001). Conclusion: When patients with SMACS secondary to chronic constipation have Lee's triple symptoms and triple anatomy anomaly, the triple combination treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation should be applied.}, }
@article {pmid31958884, year = {2020}, author = {Xiang, L and Ding, X and Li, Q and Wu, X and Dai, M and Long, C and He, Z and Cui, B and Zhang, F}, title = {Efficacy of faecal microbiota transplantation in Crohn's disease: a new target treatment?.}, journal = {Microbial biotechnology}, volume = {13}, number = {3}, pages = {760-769}, pmid = {31958884}, issn = {1751-7915}, mesh = {Adult ; *Crohn Disease/therapy ; *Fecal Microbiota Transplantation/standards ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult ; }, abstract = {The efficacy of faecal microbiota transplantation (FMT) in Crohn's disease (CD) remains unclear due to lack of data. This study aimed to assess the value of FMT in treating CD-related clinical targets. The use of FMT for CD as a registered trial (NCT01793831) was performed between October 2012 and December 2017. Seven therapeutic targets included abdominal pain, diarrhoea, hematochezia, fever, steroid-dependence, enterocutaneous fistula and active perianal fistula. Each target was recorded as 1 (yes) or 0 (no) during the long-term follow-up for each patient. The primary outcome was the rate of improvement in each therapeutic target. Overall, 174 patients completed the follow-up. The median follow-up duration was 43 (interquartile range, 28-59) months. The median score of the total targets was 2 (range, 1-4) before FMT, and it decreased significantly at 1, 3, 6, 12, 24 and 36 months after FMT (P < 0.001 respectively). At 1 month after FMT, 72.7% (101/139), 61.6% (90/146), 76% (19/25) and 70.6% (12/17) of patients achieved improvement in abdominal pain, diarrhoea, hematochezia and fever respectively. Furthermore, 50% (10/20) of steroid-dependent patients achieved steroid-free remission after FMT. The present findings indicate that it is important to understand the efficacy of FMT in CD as a targeted therapy, especially for abdominal pain, hematochezia, fever and diarrhoea.}, }
@article {pmid31958843, year = {2020}, author = {Centor, RM and Drekonja, DM}, title = {Web Exclusive. Annals On Call - Fecal Transplantation for C difficile.}, journal = {Annals of internal medicine}, volume = {172}, number = {2}, pages = {OC1}, doi = {10.7326/A19-0022}, pmid = {31958843}, issn = {1539-3704}, }
@article {pmid31958765, year = {2020}, author = {Chen, H and Zhang, F and Li, R and Liu, Y and Wang, X and Zhang, X and Xu, C and Li, Y and Guo, Y and Yao, Q}, title = {Berberine regulates fecal metabolites to ameliorate 5-fluorouracil induced intestinal mucositis through modulating gut microbiota.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {124}, number = {}, pages = {109829}, doi = {10.1016/j.biopha.2020.109829}, pmid = {31958765}, issn = {1950-6007}, mesh = {Animals ; Berberine/*pharmacology ; Cytokines/drug effects ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Fluorouracil/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Intestinal Mucosa/*drug effects ; Intestines/drug effects ; Male ; Rats, Sprague-Dawley ; }, abstract = {Berberine (BBR) is an isoquinoline alkaloid, which has been used in the treatment of intestinal mucositis. However, BBR on chemotherapy-induced mucositis in cancer patients remains largely unknown. Here, we investigated the effect of BBR on intestinal mucositis induced by 5-fluorouracil (5-Fu) using rat model. We detected the degree of intestinal mucosal damage and inflammatory response in 5-Fu treated rats with or without BBR administration, and investigated the changes of fecal metabolites and gut microbiota using [1]H NMR spectroscopy and 16S rRNA. The mechanism was further explored by fecal microbiota transplantation (FMT). Results showed that BBR treated rats displayed less weight loss, lower diarrhea score and longer colon length in 5-Fu treated rats. Meanwhile, BBR treatment significantly increased the expression of Occludin in ileum and decreased the d-lactate content in serum. Moreover, the expression of IL-1β, IL-6 and TNF-α in ileum were suppressed by BBR treatment. The pattern of fecal metabolism changed obviously after treated with 5-Fu, which was reversed by BBR. Importantly, BBR significantly increased the levels of butyrate and glutamine in feces from 5-Fu treated rats. In terms of gut microbiota, BBR enriched the relative abundance of Firmicutes and decreased Proteobacteria at the phylum level. Meanwhile, BBR increased the propotion of unclassified_f_ Porphyromonadaceae, unclassified_f_ Lachnospiraceae, Lactobacillus, unclassified_o_ Clostridiales, Ruminococcus, Prevotella, Clostridium IV, and decreased Escherichia/Shigella at the genera level. Furthermore, principal component analysis (PCA) showed that fecal transplantation led to changes in fecal metabolites. Fecal transplantation from BBR treated rats had low diarrhea score, reduced inflammatory response in ileum, and relieved intestinal mucosal injury, which may be caused by the increased of butyrate level in fecal metabolites. In conclusion, our study provides evidence that BBR regulates fecal metabolites to ameliorate 5-Fu induced intestinal mucositis by modifying gut microbiota.}, }
@article {pmid31957588, year = {2019}, author = {Ossorio, PN and Zhou, Y}, title = {FMT and Microbial Medical Products: Generating High-Quality Evidence through Good Governance.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {505-523}, doi = {10.1177/1073110519897727}, pmid = {31957588}, issn = {1748-720X}, mesh = {Biological Products/*therapeutic use ; *Clinical Trials as Topic ; *Data Accuracy ; Drug Approval/*legislation &amp; jurisprudence ; *Fecal Microbiota Transplantation ; Government Regulation ; Humans ; Policy ; United States ; United States Food and Drug Administration/legislation &amp; jurisprudence ; }, abstract = {This article argues that current data for the safety and efficacy of fecal microbiota transplants as a treatment for any indication, including recurrent Clostridioides difficile infection, is low-quality. It develops a governance proposal that encourages production of high-quality evidence by incentivizing well-designed RCTs of stool and stoolderived microbial products. The proposal would require that FDA change its current enforcement approach, but it would not require any change in statutes or regulations.}, }
@article {pmid31957587, year = {2019}, author = {Khoruts, A and Hoffmann, DE and Palumbo, FB}, title = {The Impact of Regulatory Policies on the Future of Fecal Microbiota Transplantation.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {482-504}, doi = {10.1177/1073110519897726}, pmid = {31957587}, issn = {1748-720X}, mesh = {Biological Products ; Clostridium Infections/*therapy ; Drug Approval/*legislation &amp; jurisprudence ; Drugs, Investigational/*therapeutic use ; *Fecal Microbiota Transplantation ; *Government Regulation ; History, 20th Century ; History, 21st Century ; Humans ; Orphan Drug Production ; Policy Making ; United States ; United States Food and Drug Administration/legislation &amp; jurisprudence ; }, abstract = {In this article, the authors explore the impact of a potential future regulatory decision by FDA whether or not to continue its enforcement discretion policy allowing physicians to perform, and stool banks to sell, stool product for fecal microbiota transplantation as a treatment for recurrent Clostridium Difficile infection without an Investigative New Drug (IND) application. The paper looks at the Agency's regulatory options in light of the current gut microbiota based products that are in the FDA pipeline for drug approval and the potential impact and repercussions of their approval on FDA action. In laying out FDA's options we consider the implications of market exclusivity and off-label use of newly approved drugs. Ultimately, we explore the potential impact of FDA's decision on patients, research, and innovation.}, }
@article {pmid31957585, year = {2019}, author = {Hoffmann, DE}, title = {Introduction: The Promise and Challenges of Microbiome-Based Therapies.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {476-481}, doi = {10.1177/1073110519897725}, pmid = {31957585}, issn = {1748-720X}, mesh = {Clinical Trials as Topic ; *Dissent and Disputes ; Fecal Microbiota Transplantation/ethics/*trends ; Female ; *Government Regulation ; Humans ; Male ; Microbiota ; *Policy ; United States ; United States Food and Drug Administration/*legislation &amp; jurisprudence ; Vagina/microbiology ; }, }
@article {pmid31957577, year = {2019}, author = {DeLong, K and Zulfiqar, F and Hoffmann, DE and Tarzian, AJ and Ensign, LM}, title = {Vaginal Microbiota Transplantation: The Next Frontier.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {555-567}, doi = {10.1177/1073110519897731}, pmid = {31957577}, issn = {1748-720X}, mesh = {Biological Therapy/*ethics/*methods/*trends ; Body Fluids/*microbiology ; Clinical Trials as Topic ; Ethics, Research ; Female ; Government Regulation ; Humans ; *Microbiota ; Research Design ; United States ; United States Food and Drug Administration ; Vagina/*microbiology ; Vaginosis, Bacterial/*therapy ; }, abstract = {The success of fecal microbiota transplantation (FMT) as a treatment for Clostrioides difficile infection (CDI) has stirred excitement about the potential for microbiota transplantation as a therapy for a wide range of diseases and conditions. In this article, we discuss vaginal microbiota transplantation (VMT) as "the next frontier" in microbiota transplantation and identify the medical, regulatory, and ethical challenges related to this nascent field. We further discuss what we anticipate will be the first context for testing VMT in clinical trials, prevention of the recurrence of a condition referred to as bacterial vaginosis (BV). We also compare clinical aspects of VMT with FMT and comment on how VMT may be similar to or different from FMT in ways that may affect research design and regulatory decisions.}, }
@article {pmid31957576, year = {2019}, author = {Murray, TS and Herbst, J}, title = {The Ethics of Fecal Microbiota Transplant as a Tool for Antimicrobial Stewardship Programs.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {541-554}, doi = {10.1177/1073110519897730}, pmid = {31957576}, issn = {1748-720X}, mesh = {Anti-Bacterial Agents/pharmacology ; Antimicrobial Stewardship/*ethics/legislation &amp; jurisprudence/organization &amp; administration ; Clinical Trials as Topic ; *Drug Resistance, Multiple, Bacterial ; *Ethics, Clinical ; *Ethics, Institutional ; *Ethics, Research ; Fecal Microbiota Transplantation/*ethics ; Female ; Humans ; Male ; }, abstract = {Multidrug resistant organisms (MDROs) are a public health threat that have reduced the effectiveness of many available antibiotics. Antimicrobial stewardship programs (ASPs) have been tasked with reducing antibiotic use and therefore the emergence of MDROs. While fecal microbiota transplant (FMT) has been proposed as therapy to reduce patient colonization of MDROs, this will require additional evidence to support an expansion of the current clinical indication for FMT. This article discusses the evidence and ethics of the expanded utilization of FMT by ASPs for reasons other than severe recurrent or refractory Clostridioides (formerly Clostridium) difficile infection.}, }
@article {pmid31957572, year = {2019}, author = {Scheeler, A}, title = {Where Stool is a Drug: International Approaches to Regulating the use of Fecal Microbiota for Transplantation.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {524-540}, doi = {10.1177/1073110519897729}, pmid = {31957572}, issn = {1748-720X}, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*classification ; *Government Regulation ; Humans ; *International Law ; Internationality/*legislation &amp; jurisprudence ; Legislation, Drug/standards ; }, abstract = {Regulatory agencies vary widely in their classification of FMT, with significant impact on patient access. This article conducts a global survey of national regulations and collates existing FMT classification statuses, ultimately suggesting that the human cell and tissue product designation best fits FMT's characteristics and that definitional objectives to that classification may be overcome.}, }
@article {pmid31955527, year = {2020}, author = {Illiano, P and Brambilla, R and Parolini, C}, title = {The mutual interplay of gut microbiota, diet and human disease.}, journal = {The FEBS journal}, volume = {287}, number = {5}, pages = {833-855}, doi = {10.1111/febs.15217}, pmid = {31955527}, issn = {1742-4658}, mesh = {Brain/metabolism ; Cardiovascular Diseases/metabolism/microbiology ; Central Nervous System/metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Neoplasms/metabolism/microbiology ; Prebiotics ; Probiotics ; }, abstract = {The intestinal milieu harbours the gut microbiota, consisting of a complex community of bacteria, archaea, fungi, viruses and protozoans that bring to the host organism an endowment of cells and genes more numerous than its own. In the last 10 years, mounting evidence has highlighted the prominent influence of the gut mutualistic bacterial communities on human health. Microbial colonization occurs alongside with immune system development and plays a role in intestinal physiology. The community of the gut microbiota does not undergo significant fluctuations throughout adult life. However, bacterial infections, antibiotic treatment, lifestyle, surgery and diet might profoundly affect it. Gut microbiota dysbiosis, defined as marked alterations in the amount and function of the intestinal microorganisms, is correlated with the aetiology of chronic noncommunicable diseases, ranging from cardiovascular, neurologic, respiratory and metabolic illnesses to cancer. In this review, we focus on the interplay among gut microbiota, diet and host to provide a perspective on the role of microbiota and their unique metabolites in the pathogenesis and/or progression of various human disorders. We discuss interventions based on microbiome studies, that is faecal microbiota transplantation, probiotics and prebiotics, to introduce the concept that correcting gut dysbiosis can ameliorate disease symptoms, thus offering a new approach towards disease treatment.}, }
@article {pmid31952909, year = {2020}, author = {Papanicolas, LE and Gordon, DL and Wesselingh, SL and Rogers, GB}, title = {Improving Risk-Benefit in Faecal Transplantation through Microbiome Screening.}, journal = {Trends in microbiology}, volume = {28}, number = {5}, pages = {331-339}, doi = {10.1016/j.tim.2019.12.009}, pmid = {31952909}, issn = {1878-4380}, mesh = {Clostridioides difficile/pathogenicity ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Mass Screening ; Symbiosis/physiology ; }, abstract = {Faecal microbiota transplantation (FMT) has been shown to be effective in the treatment of a growing number of conditions, and its clinical use continues to rise. However, recent cases of antibiotic-resistant pathogen transmission through FMT, resulting in at least one case of fatal sepsis, highlight the need to reevaluate current donor screening practices. Commensal gut microbes profoundly influence infection risk but are not routinely assessed in donor stool. Extending the assessment of donor material beyond pathogen populations to include the composition and structure of the wider faecal microbiota has the potential to reduce infectious complications in FMT recipients.}, }
@article {pmid31951695, year = {2019}, author = {Parco, S and Benericetti, G and Vascotto, F and Palmisciano, G}, title = {Microbiome and diversity indices during blood stem cells transplantation - new perspectives?.}, journal = {Central European journal of public health}, volume = {27}, number = {4}, pages = {335-339}, doi = {10.21101/cejph.a5393}, pmid = {31951695}, issn = {1210-7778}, mesh = {Child ; Gastrointestinal Microbiome/immunology ; Graft vs Host Disease/*microbiology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Microbiota/*immunology ; Mouth/immunology/microbiology ; }, abstract = {OBJECTIVE: The human body is colonized by bacteria, fungi and viruses. Resident commensal bacteria are a fundamental line of resistance to colonization by exogenous microbes. They actively regulate the production of nutrients by the host through a negative feedback mechanism, in order to prevent the availability of nutrients for potential pathogens. While only a small fraction of these microorganism may be pathogenic, the relationship between host and commensal microbiome is now studied as a whole, impacting several aspects of the host biology. Some studies have made clear the progresses in examining the role of microbiome on transplants and graft versus host disease (GVHD) severity and its pathogenesis: the risk of complications from allogenic hematopoietic stem cells transplantation (HSCT) is greater with the highest mortality if a patient has a lower bacterial diversity in the gut prior to the transplantation process beginning. Microbiota-associated molecular patterns are directly recognized by pathogen recognition receptors. The development of molecular methods has greatly expanded our knowledge of the composition and function of the microbiome in health and disease, shortening the response times vs. microbiological culture tests. The gut flora can make the difference when it comes to allo-HSCT. The aim of the study was to monitor microbiome of 10 children during allo-HSCT.<br><br>METHODS: Oral specimens and gut faecal microbiome (100 grams) samples were collected at 2, 16, 24 days. The samples were analysed by polymerase chain reaction and primary sequencing was done. To calculate the biodiversity of microbiome the Shannon index and the Observed species index were chosen.<br><br>RESULTS: Our study suggests some differences in the diversity indices (DIs) in 5 children affected by GVHD vs. not affected. The DIs in oral and faecal specimens show in all patients a diminution in the post-transplant phase with an improvement in species diversity after 16 days from the transplant. The Observed species index in faeces specimens after 16 days was higher in patients which had not GVHD; moreover, patients with GVHD showed a deterioration at 24 days. Oral specimens after 24 days showed a parallel trend in the two groups. The Shannon index shows a downward trend in faeces specimens of the children with GVHD at 24 days; the children without GVHD recover a good trend of entropy. Oral specimens at 24 days show low entropy in the two groups. Very aggressive bacterial species as Cronobacter and Routella in the faeces specimens of a child had not serious consequences for disease status: Cronobacter were not present 24 days after transplantation.<br><br>CONCLUSIONS: The data show the microbial metabolome could have an impact on patients with GVHD vs. no GVHD. A better understanding of the role of the oral and gut microbiome in GVHD can give directions to move towards the development of innovative approaches for preventing GVHD following allo-HCT, reducing also antibiotic therapy.}, }
@article {pmid31950808, year = {2019}, author = {Blanchaert, C and Strubbe, B and Peeters, H}, title = {Fecal microbiota transplantation in ulcerative colitis.}, journal = {Acta gastro-enterologica Belgica}, volume = {82}, number = {4}, pages = {519-528}, pmid = {31950808}, issn = {1784-3227}, mesh = {Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Colitis, Ulcerative/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Intestines/microbiology ; *Microbiota ; Treatment Outcome ; }, abstract = {BACKGROUND/STUDY AIMS: Fecal microbiota transplantation (FMT), a treatment aiming to restore dysbiosis by transferring stool from a healthy donor into the patient, has cure rates up to 90% in the management of recurrent Clostridium difficile (C. difficile) diarrhea. This paper tries to determine whether FMT is safe and effective in the treatment of ulcerative colitis, and what the potential characteristics could be of a 'super donor'.<br><br>METHODS: The PubMed database was searched using the term fecal microbiota transplantation inflammatory bowel disease. Only articles discussing the use of FMT in the treatment of ulcerative colitis were withheld. Finally, 31 original studies (10 case reports, 17 open label trials, 4 randomized controlled trials (RCTs)) and 1 meta-analysis were included.<br><br>RESULTS: So far 4 RCTs have investigated the effectiveness of FMT in treating UC. Three RCTs reported a significant difference between FMT and a control group, achieving clinical remission in 24 to 44% of patients (vs. 5 to 20% of patients in control groups). The meta-analysis confirms that significantly more patients in the FMT-group achieve clinical remission in comparison to patients in the control group (p=0,01) : 42,1% vs. 22,6%. The composition of the gut microbiota plays an important role in the success of FMT-treatment.<br><br>CONCLUSION: FMT seems to be a promising and safe therapy in the management of UC. Further research, with larger cohorts, will be needed to confirm this and to determine the optimal FMT procedure.}, }
@article {pmid31950071, year = {2020}, author = {Oliva, A and Aversano, L and De Angelis, M and Mascellino, MT and Miele, MC and Morelli, S and Battaglia, R and Iera, J and Bruno, G and Corazziari, ES and Ciardi, MR and Venditti, M and Mastroianni, CM and Vullo, V}, title = {Persistent Systemic Microbial Translocation, Inflammation, and Intestinal Damage During Clostridioides difficile Infection.}, journal = {Open forum infectious diseases}, volume = {7}, number = {1}, pages = {ofz507}, pmid = {31950071}, issn = {2328-8957}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI.<br><br>METHODS: Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively.<br><br>RESULTS: Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P < .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values.<br><br>CONCLUSIONS: CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated.}, }
@article {pmid31948404, year = {2020}, author = {Kachlíková, M and Sabaka, P and Koščálová, A and Bendžala, M and Dovalová, Z and Stankovič, I}, title = {Comorbid status and the faecal microbial transplantation failure in treatment of recurrent Clostridioides difficile infection - pilot prospective observational cohort study.}, journal = {BMC infectious diseases}, volume = {20}, number = {1}, pages = {52}, pmid = {31948404}, issn = {1471-2334}, mesh = {Aged ; Clostridium Infections/epidemiology/microbiology/*therapy ; Cohort Studies ; Comorbidity ; Diarrhea/etiology ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Risk Factors ; Treatment Failure ; }, abstract = {BACKGROUND: Faecal microbial transplantation (FMT) is currently the most effective treatment of recurrent Clostridioides difficile infection (CDI). However, up to 20% of patients experience further recurrences after single FMT. The mechanisms that lead to FMT failure and its risk factors are poorly understood. Comorbidity is one of the risk factors of the failure of standard antibiotic therapy of recurrent CDI. It is not known if comorbidity is also associated with the risk of FMT failure.<br><br>METHODS: We conducted a prospective observational cohort study in order to elucidate if comorbid status is associated with FMT failure. Patients with microbiologically proven recurrent CDI were recruited and underwent FMT via retention enema. Patients were followed up for 12&#x2009;weeks after FMT for signs and symptoms of CDI recurrence. Single FMT failure was defined as recurrence of diarrhoea and a positive stool test for the presence of C. difficile antigen or toxin at any time point during the 12&#x2009;weeks of follow-up. We assessed the association of single FMT failure with possible manageable and unmanageable risk factors. As a surrogate of comorbid status, we used Charlson Comorbidity Index (CCI)&#x2009;&#x2265;&#x2009;7.<br><br>RESULTS: A total of 60 patients that underwent single FMT (34 women, 26 men) were included in the study. Overall, 15 patients (25%) experienced single FMT failure. 24 patients (40%) had CCI&#x2009;&#x2265;&#x2009;7, and 45.0% patients with CCI&#x2009;&#x2265;&#x2009;7 experienced failure of single FMT. Patients who experienced single FMT failure had a significantly higher CCI and significantly lower albumin concentration as compared to patients who experienced single FMT success. There was no difference in age, C-reactive protein concentration, leukocyte count and time from FMT to first defecation. In multivariate analysis, CCI&#x2009;&#x2265;&#x2009;7 was positively associated with the failure of single FMT. Analysis was controlled for sex, age, time from FMT to first defecation, concomitant PPI therapy, severe CDI, hospital-acquired infection and albumin concentration.<br><br>CONCLUSIONS: Comorbid status surrogated by CCI is positively associated with the failure of single FMT in the treatment of recurrent CDI.}, }
@article {pmid31942825, year = {2020}, author = {Ho, J and Yeoh, YK and Barua, N and Chen, Z and Lui, G and Wong, SH and Yang, X and Chan, MC and Chan, PK and Hawkey, PM and Ip, M}, title = {Systematic review of human gut resistome studies revealed variable definitions and approaches.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1700755}, pmid = {31942825}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/classification/*drug effects/*genetics ; Drug Resistance, Bacterial/*genetics ; Gastrointestinal Microbiome/*drug effects/*genetics ; Gastrointestinal Tract/microbiology ; Genes, Bacterial ; Humans ; }, abstract = {In this review, we highlight the variations of gut resistome studies, which may preclude comparisons and translational interpretations. Of 22 included studies, a range of 12 to 2000 antibiotic resistance (AR) genes were profiled. Overall, studies defined a healthy gut resistome as subjects who had not taken antibiotics in the last three to 12 months prior to sampling. In studies with de novo assembly, AR genes were identified based on variable nucleotide or amino acid sequence similarities. Different marker genes were used for defining resistance to a given antibiotic class. Validation of phenotypic resistance in the laboratory is frequently lacking. Cryptic resistance, collateral sensitivity and the interaction with repressors or promotors were not investigated. International consensus is needed for selecting marker genes to define resistance to a given antibiotic class in addition to uniformity in phenotypic validation and bioinformatics pipelines.}, }
@article {pmid31941900, year = {2020}, author = {Siranosian, BA and Tamburini, FB and Sherlock, G and Bhatt, AS}, title = {Acquisition, transmission and strain diversity of human gut-colonizing crAss-like phages.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {280}, pmid = {31941900}, issn = {2041-1723}, support = {K08 CA184420/CA/NCI NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteriophages/*genetics/physiology ; Bacteroides/virology ; Biodiversity ; Cesarean Section ; Fecal Microbiota Transplantation ; Feces/*virology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Infant ; Metagenome ; Polymorphism, Single Nucleotide ; Tissue Donors ; }, abstract = {CrAss-like phages are double-stranded DNA viruses that are prevalent in human gut microbiomes. Here, we analyze gut metagenomic data from mother-infant pairs and patients undergoing fecal microbiota transplantation to evaluate the patterns of acquisition, transmission and strain diversity of crAss-like phages. We find that crAss-like phages are rarely detected at birth but are increasingly prevalent in the infant microbiome after one month of life. We observe nearly identical genomes in 50% of cases where the same crAss-like clade is detected in both the mother and the infant, suggesting vertical transmission. In cases of putative transmission of prototypical crAssphage (p-crAssphage), we find that a subset of strains present in the mother are detected in the infant, and that strain diversity in infants increases with time. Putative tail fiber proteins are enriched for nonsynonymous strain variation compared to other genes, suggesting a potential evolutionary benefit to maintaining strain diversity in specific genes. Finally, we show that p-crAssphage can be acquired through fecal microbiota transplantation.}, }
@article {pmid31941505, year = {2020}, author = {Kauff, DW and Roth, YDS and Bettzieche, RS and Kneist, W}, title = {Fecal incontinence after total mesorectal excision for rectal cancer-impact of potential risk factors and pelvic intraoperative neuromonitoring.}, journal = {World journal of surgical oncology}, volume = {18}, number = {1}, pages = {12}, pmid = {31941505}, issn = {1477-7819}, mesh = {Aged ; Chemoradiotherapy/adverse effects ; Fecal Incontinence/epidemiology/*etiology/prevention &amp; control ; Female ; Follow-Up Studies ; Humans ; Intraoperative Neurophysiological Monitoring ; Male ; Middle Aged ; Neoadjuvant Therapy/adverse effects ; Pelvis/innervation ; Postgastrectomy Syndromes/epidemiology/*etiology/prevention &amp; control ; Proctectomy/*adverse effects ; Prospective Studies ; Rectal Neoplasms/drug therapy/radiotherapy/*surgery ; Risk Factors ; }, abstract = {BACKGROUND: Fecal incontinence frequently occurs after total mesorectal excision for rectal cancer. This prospective study analyzed predictive factors and the impact of pelvic intraoperative neuromonitoring at different follow-up intervals.<br><br>METHODS: Fifty-two patients were included undergoing total mesorectal excision for rectal cancer, and 29 under control of pelvic intraoperative neuromonitoring. Fecal incontinence was assessed using the Wexner Score at 3 and 6&#x2009;months after stoma closure (follow-ups 1 and 2) as well as 1 and 2 years after surgery (follow-ups 3 and 4). Risk factors were identified by means of logistic regression.<br><br>RESULTS: New onset of fecal incontinence was significantly lower in the neuromonitoring group at each follow-up (follow-up 1: 2 of 29 patients (7%) vs. 8 of 23 (35%), (p = 0.014); follow-up 2: 3 of 29 (10%) vs. 9 of 23 (39%), (p = 0.017); follow-up 3: 5 of 29 (17%) vs. 11 of 23 (48%), p = 0.019; follow-up 4: 6 of 28 (21%) vs. 11 of 22 (50%), p = 0.035). Non-performance of neuromonitoring was found to be an independent predictor for fecal incontinence throughout the survey. Neoadjuvant chemoradiotherapy was an independent predictor in the further course 1 and 2 years after surgery.<br><br>CONCLUSIONS: Performance of pelvic intraoperative neuromonitoring is associated with significantly lower rates of fecal incontinence. Neoadjuvant chemoradiotherapy was found to have negative late effects. This became evident 1 year after surgery.}, }
@article {pmid31941102, year = {2020}, author = {Xiang, Q and Wu, X and Pan, Y and Wang, L and Cui, C and Guo, Y and Zhu, L and Peng, J and Wei, H}, title = {Early-Life Intervention Using Fecal Microbiota Combined with Probiotics Promotes Gut Microbiota Maturation, Regulates Immune System Development, and Alleviates Weaning Stress in Piglets.}, journal = {International journal of molecular sciences}, volume = {21}, number = {2}, pages = {}, pmid = {31941102}, issn = {1422-0067}, support = {31772609//National Natural Science Foundation of China/ ; 2019-620-000-001-30//Hubei Agricultural Sciences and Technology Innovation Center/ ; CARS-36//China Agriculture Research System/ ; }, mesh = {Animals ; Animals, Newborn ; Clostridium butyricum/*immunology ; Cytokines/immunology ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Probiotics/*pharmacology ; Saccharomyces boulardii/*immunology ; *Stress, Physiological/drug effects/immunology ; Swine ; Weaning ; }, abstract = {Previous studies have suggested that immune system development and weaning stress are closely related to the maturation of gut microbiota. The early-life period is a "window of opportunity" for microbial colonization, which potentially has a critical impact on the development of the immune system. Fecal microbiota transplantation (FMT) and probiotics are often used to regulate gut microbial colonization. This study aims to test whether early intervention with FMT using fecal microbiota from gestation sows combined with Clostridium butyricum and Saccharomyces boulardii (FMT-CS) administration could promote the maturation of gut microbiota and development of immune system in piglets. Piglets were assigned to control (n = 84) and FMT-CS treatment (n = 106), which were treated with placebo and bacterial suspension during the first three days after birth, respectively. By 16S rRNA gene sequencing, we found that FMT-CS increased the α-diversity and reduced the unweighted UniFrac distances of the OTU community. Besides, FMT-CS increased the relative abundance of beneficial bacteria, while decreasing that of opportunistic pathogens. FMT-CS also enhanced the relative abundance of genes related to cofactors and vitamin, energy, and amino acid metabolisms during the early-life period. ELISA analysis revealed that FMT-CS gave rise to the plasma concentrations of IL-23, IL-17, and IL-22, as well as the plasma levels of anti-M.hyo and anti-PCV2 antibodies. Furthermore, the FMT-CS-treated piglets showed decreases in inflammation levels and oxidative stress injury, and improvement of intestinal barrier function after weaning as well. Taken together, our results suggest that early-life intervention with FMT-CS could promote the development of innate and adaptive immune system and vaccine efficacy, and subsequently alleviate weaning stress through promoting the maturation of gut microbiota in piglets.}, }
@article {pmid31940312, year = {2020}, author = {Schmidt, EKA and Torres-Espin, A and Raposo, PJF and Madsen, KL and Kigerl, KA and Popovich, PG and Fenrich, KK and Fouad, K}, title = {Fecal transplant prevents gut dysbiosis and anxiety-like behaviour after spinal cord injury in rats.}, journal = {PloS one}, volume = {15}, number = {1}, pages = {e0226128}, pmid = {31940312}, issn = {1932-6203}, support = {MOP 119281//CIHR/Canada ; }, mesh = {Animals ; Anxiety/*complications/*prevention &amp; control ; *Behavior, Animal ; Dysbiosis/*complications/microbiology/*prevention &amp; control ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Maze Learning ; Rats ; Recovery of Function ; Spinal Cord Injuries/*complications/microbiology/physiopathology/psychology ; }, abstract = {Secondary manifestations of spinal cord injury beyond motor and sensory dysfunction can negatively affect a person's quality of life. Spinal cord injury is associated with an increased incidence of depression and anxiety; however, the mechanisms of this relationship are currently not well understood. Human and animal studies suggest that changes in the composition of the intestinal microbiota (dysbiosis) are associated with mood disorders. The objective of the current study is to establish a model of anxiety following a cervical contusion spinal cord injury in rats and to determine whether the microbiota play a role in the observed behavioural changes. We found that spinal cord injury caused dysbiosis and increased symptoms of anxiety-like behaviour. Treatment with a fecal transplant prevented both spinal cord injury-induced dysbiosis as well as the development of anxiety-like behaviour. These results indicate that an incomplete unilateral cervical spinal cord injury can cause affective disorders and intestinal dysbiosis, and that both can be prevented by treatment with fecal transplant therapy.}, }
@article {pmid31938969, year = {2020}, author = {Wang, G and Joel, MDM and Yuan, J and Wang, J and Cai, X and Ocansey, DKW and Yan, Y and Qian, H and Zhang, X and Xu, W and Mao, F}, title = {Human umbilical cord mesenchymal stem cells alleviate inflammatory bowel disease by inhibiting ERK phosphorylation in neutrophils.}, journal = {Inflammopharmacology}, volume = {28}, number = {2}, pages = {603-616}, pmid = {31938969}, issn = {1568-5608}, support = {81670502//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Dextran Sulfate ; Disease Models, Animal ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; HL-60 Cells ; Humans ; Inflammatory Bowel Diseases/physiopathology/*therapy ; Mesenchymal Stem Cell Transplantation/*methods ; Mesenchymal Stem Cells/cytology ; Mice ; Mice, Inbred C57BL ; Neutrophils/*metabolism ; Phosphorylation/physiology ; Signal Transduction ; Umbilical Cord/cytology ; }, abstract = {Inflammatory bowel disease (IBD) can be caused by a variety of factors, including hereditary and environmental influences, that lead to dysfunction of the intestinal immune system. Mesenchymal stem cells (MSCs) exhibit important regulatory roles in relieving inflammation and repairing damaged tissues. Although neutrophils are important participants in the development of inflammatory reactions, they are also essential for maintaining intestinal balance during the process of mitigation of IBD by MSCs. Here, we constructed a dextran sulfate sodium (DSS)-induced mouse IBD model and evaluated the effects of treatment with human umbilical cord MSCs. Mouse body weight, faecal traits, colon/spleen gross morphology, tissue histology and immunohistochemical staining, and inflammatory factors were analysed. Magnetic beads were used to sort infiltrating neutrophils from intestinal tissues, and their phenotypes were identified. The neutrophil inflammatory environment was also simulated in vitro, and signalling pathways involved in MSC regulation of neutrophil phenotype were analysed. Human umbilical cord MSCs effectively alleviated DSS-induced weight loss, colon shortening, and intestinal mucosal injury, and reduced clinical disease activity index. The number of neutrophils that infiltrated the intestines of mice treated with human umbilical cord MSCs were decreased and polarised toward the N2 phenotype; at the same time, ERK phosphorylation was inhibited. In vitro experiments showed that addition of the ERK phosphorylation inhibitor, PD98059, down-regulated the expression of N1 neutrophils, while up-regulating that of N2 neutrophils. The colon tissues from patients with IBD were infiltrated with neutrophils. Further, relative to healthy controls, the markers of N1 neutrophils (ICAM-1, FAS, and CCL3) were highly expressed in colon tissues from patients with IBD, whereas the markers of N2 neutrophils (VEGF, CCL2, and CXCR4) were almost undetectable. In conclusion, during alleviation of IBD, human umbilical cord MSCs polarise neutrophils toward the "N2" phenotype by inhibiting activation of ERK signalling.}, }
@article {pmid31938827, year = {2020}, author = {Antonelli, M and Martin-Loeches, I and Dimopoulos, G and Gasbarrini, A and Vallecoccia, MS}, title = {Clostridioides difficile (formerly Clostridium difficile) infection in the critically ill: an expert statement.}, journal = {Intensive care medicine}, volume = {46}, number = {2}, pages = {215-224}, pmid = {31938827}, issn = {1432-1238}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/drug effects/*pathogenicity ; Clostridium Infections/*physiopathology ; Cross Infection ; Fecal Microbiota Transplantation ; Humans ; Infection Control/methods/standards ; Intensive Care Units/organization &amp; administration ; Risk Factors ; Tomography, X-Ray Computed/methods ; }, abstract = {Clostridioides difficile (formerly Clostridium difficile) infection (CDI) represents a worrisome condition, often underestimated, with severe clinical presentations, frequently requiring intensive care unit (ICU) admission. The aim of the present expert statement was to give an overview of the management of CDI in critically ill patients, for whom CDI represents a redoubtable problem, in large part related to the use and abuse of antibiotics. The available knowledge about pathophysiology, risk factors, diagnosis and treatment concerning critical care patients affected by CDI has been reviewed, even though most of the existing information come from studies performed outside the ICU and the evidence on several issues in this specific context is scarce. The adoption of potential preventive and therapeutic strategies aimed to stem the phenomenon were discussed, including the faecal microbiota transplantation. This possibility could represent a highly interesting option in critically ill patients, but current evidence is limited and future well designed studies are needed. A special insight on the specific challenges that the ICU physicians may face caring for the critically ill patients with CDI was also proposed.}, }
@article {pmid31937933, year = {2020}, author = {Zhang, PP and Li, LL and Han, X and Li, QW and Zhang, XH and Liu, JJ and Wang, Y}, title = {Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice.}, journal = {Acta pharmacologica Sinica}, volume = {41}, number = {5}, pages = {678-685}, pmid = {31937933}, issn = {1745-7254}, mesh = {Akkermansia/metabolism ; Animals ; Clostridiales/*metabolism ; Desulfovibrio/*metabolism ; Diabetes Mellitus, Type 2/*metabolism/therapy ; Disease Models, Animal ; Dyslipidemias/*metabolism/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; }, abstract = {Fecal microbiota transplantation (FMT) has become an effective strategy to treat metabolic diseases, including type 2 diabetes mellitus (T2DM). We previously reported that the intestinal microbiome had significant difference between individuals with normal glucose tolerance and T2DM in Chinese Kazak ethnic group. In this study, we investigated the effects of transplanted fecal bacteria from Kazaks with normal glucose tolerance (KNGT) in db/db mice. The mice were treated with 0.2 mL of fecal bacteria solution from KNGT daily for 10 weeks. We showed that the fecal bacteria from KNGT successfully colonized in the intestinal tract of db/db mice detected on day 14. In the FMT-treated db/db mice, the levels of fasting blood glucose, postprandial glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol were significantly downregulated, whereas high-density lipoprotein-cholesterol levels were upregulated. In the FMT-treated db/db mice, Desulfovibrio and Clostridium coccoides levels in gut were significantly decreased, but the fecal levels of Akkermansia muciniphila and colon histone deacetylase-3 (HDAC3) protein expression were increased. At 8 weeks, both intestinal target bacteria and HDAC3 were correlated with glycolipid levels; Akkermansia muciniphila level was positively correlated with HDAC3 protein expression (r = +0.620, P = 0.037). Our results suggest that fecal bacteria from KNGT could potentially be used to treat diabetic patients.}, }
@article {pmid31936237, year = {2020}, author = {Chang, CW and Lee, HC and Li, LH and Chiang Chiau, JS and Wang, TE and Chuang, WH and Chen, MJ and Wang, HY and Shih, SC and Liu, CY and Tsai, TH and Chen, YJ}, title = {Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer.}, journal = {International journal of molecular sciences}, volume = {21}, number = {2}, pages = {}, pmid = {31936237}, issn = {1422-0067}, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Colorectal Neoplasms/complications/*drug therapy/microbiology/pathology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Fluorouracil/adverse effects/pharmacology ; Gastrointestinal Microbiome/drug effects/genetics ; Gene Expression Regulation, Neoplastic/drug effects ; Heterografts ; Humans ; Intestinal Diseases/chemically induced/microbiology/pathology/*prevention &amp; control ; Intestines/drug effects/injuries/*microbiology ; Leucovorin/adverse effects/pharmacology ; Mice ; Organoplatinum Compounds/adverse effects/pharmacology ; Oxaliplatin/adverse effects/pharmacology ; Toll-Like Receptors/genetics ; }, abstract = {FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), a 5-fluorouracil (5-FU)-based chemotherapy regimen, is one of most common therapeutic regimens for colorectal cancer. However, intestinal mucositis is a common adverse effect for which no effective preventive strategies exist. Moreover, the efficacy and the safety of fecal microbiota transplants (FMT) in cancer patients treated with anti-neoplastic agents are still scant. We investigated the effect of FMT on FOLFOX-induced mucosal injury. BALB/c mice implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered FMT daily during and two days after five-day injection of FOLFOX regimen for seven days. Administration of FOLFOX significantly induced marked levels of diarrhea and intestinal injury. FMT reduced the severity of diarrhea and intestinal mucositis. Additionally, the number of goblet cells and zonula occludens-1 decreased, while apoptotic and NF-κB-positive cells increased following FOLFOX treatment. The expression of toll-like receptors (TLRs), MyD88, and serum IL-6 were upregulated following FOLFOX treatment. These responses were attenuated following FMT. The disrupted fecal gut microbiota composition was also restored by FMT after FOLFOX treatment. Importantly, FMT did not cause bacteremia and safely alleviated FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism may involve the gut microbiota TLR-MyD88-NF-κB signaling pathway in mice with implanted colorectal carcinoma cells.}, }
@article {pmid31934800, year = {2020}, author = {Harris, C and Kim, PT and Waterhouse, D and Feng, Z and Niergarth, J and Lee, CH}, title = {Precision medicine and gut dysbiosis.}, journal = {Healthcare management forum}, volume = {33}, number = {3}, pages = {107-110}, doi = {10.1177/0840470419899426}, pmid = {31934800}, issn = {0840-4704}, mesh = {Canada ; Clostridium Infections/*therapy ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Health Status ; Humans ; *Precision Medicine ; Quality of Life ; }, abstract = {Clostridioides difficile Infection (CDI) is a leading cause of healthcare-associated infections in Canada, affecting the gastrointestinal tract which can lead to fever, abdominal pain, and diarrhea. Effective treatment for patients with Recurrent CDI (rCDI) can be achieved by Fecal Microbiota Transplantation (FMT) by introducing the gut micro-organisms of a healthy person (donor) into the bowel of the affected individual. Research has shown that an increase in the specific bacterial phyla post-FMT may be partly responsible for this gut restoration and elimination of disease. Furthermore, in understanding the key bacteria associated with successful FMT, full treatment plans can be developed for the individual needs of the patient by matching an infected individual with a donor possessing ideal microbiota for the specific patient. This development of precision medicine and more systematic adoption of FMT can be the next step toward more rapid resolution of rCDI.}, }
@article {pmid31929989, year = {2019}, author = {Gupta, N and Hanauer, SB}, title = {One man's trash-another man's treasure: fecal transplantation.}, journal = {Hepatobiliary surgery and nutrition}, volume = {8}, number = {6}, pages = {623-625}, pmid = {31929989}, issn = {2304-3881}, }
@article {pmid31928131, year = {2020}, author = {Bowerman, KL and Varelias, A and Lachner, N and Kuns, RD and Hill, GR and Hugenholtz, P}, title = {Continuous pre- and post-transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wild-type mice.}, journal = {Gut microbes}, volume = {11}, number = {4}, pages = {754-770}, pmid = {31928131}, issn = {1949-0984}, mesh = {Acute Disease ; Animals ; Bacteroidetes/growth &amp; development ; Disease Susceptibility ; Dysbiosis ; Enterobacteriaceae/growth &amp; development/pathogenicity ; Feces/microbiology ; *Gastrointestinal Microbiome ; Graft vs Host Disease/*etiology/microbiology ; *Hematopoietic Stem Cell Transplantation ; Housing, Animal ; Metagenome ; Mice ; Mice, Inbred C57BL ; Virulence Factors/metabolism ; }, abstract = {OBJECTIVE: The gut microbiome plays a key role in the development of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. Here we investigate the individual contribution of the pre- and post-transplant gut microbiome to acute GVHD using a well-studied mouse model.<br><br>DESIGN: Wild-type mice were cohoused with IL-17RA[-/ -] mice, susceptible to hyperacute GVHD, either pre- or post-transplant alone or continuously (i.e., pre- and post-transplant). Fecal samples were collected from both WT and IL-17RA[-/ -] mice pre- and post-cohousing and post-transplant and the microbiome analyzed using metagenomic sequencing.<br><br>RESULTS: Priming wild-type mice via cohousing pre-transplant only is insufficient to accelerate GVHD, however, accelerated disease is observed in WT mice cohoused post-transplant only. When mice are cohoused continuously, the effect of priming and exacerbation is additive, resulting in a greater acceleration of disease in WT mice beyond that seen with cohousing post-transplant only. Metagenomic analysis of the microbiome revealed pre-transplant cohousing is associated with the transfer of specific species within two as-yet-uncultured genera of the bacterial family Muribaculaceae; CAG-485 and CAG-873. Post-transplant, we observed GVHD-associated blooms of Enterobacteriaceae members Escherichia coli and Enterobacter hormaechei subsp. steigerwaltii, and hyperacute GVHD gut microbiome distinct from that associated with delayed-onset disease (>10 days post-transplant).<br><br>CONCLUSION: These results clarify the importance of the peri-transplant microbiome in the susceptibility to acute GVHD post-transplant and demonstrate the species-specific nature of this association.}, }
@article {pmid31928124, year = {2020}, author = {Ye, Z and Wu, C and Zhang, N and Du, L and Cao, Q and Huang, X and Tang, J and Wang, Q and Li, F and Zhou, C and Xu, Q and Xiong, X and Kijlstra, A and Qin, N and Yang, P}, title = {Altered gut microbiome composition in patients with Vogt-Koyanagi-Harada disease.}, journal = {Gut microbes}, volume = {11}, number = {3}, pages = {539-555}, pmid = {31928124}, issn = {1949-0984}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Adult ; Animals ; Biodiversity ; Butyrates/metabolism ; DNA, Bacterial ; Disease Models, Animal ; Dysbiosis/*microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotyping Techniques ; Humans ; Immunosuppressive Agents/therapeutic use ; Lactic Acid/metabolism ; Male ; Mice ; Prognosis ; Uveomeningoencephalitic Syndrome/*microbiology ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is a multisystemic autoimmune disorder characterized by granulomatous panuveitis. Gut microbiome has been considered to play a role in the pathogenesis of this disease but whether the alternation of gut microbiome was involved is unclear. This study was set up to identify abnormalities of gut microbiome composition in VKH disease.<br><br>RESULTS: Depleted butyrate-producing bacteria, lactate-producing bacteria and methanogens as well as enriched Gram-negative bacteria were identified in the active VKH patients, as well as in VKH patients of Mix enterotype and Bacteroides enterotype. Changes of gut microbiome in the VKH patients were partially restored after an immunosuppressive treatment. The disease susceptibility genotype HLA-DRA was associated with Bacteroides sp.2.1.33B, Paraprevotella clara, Alistipes finegoldii and Eubacterium eligens. A microbial marker profile including 40 disease-associated species was established to differentiate patients from controls. Another microbial marker profile including 37 species was found to be associated with the response to treatment. An animal experiment showed that transfer of gut microbiome from VKH patients could significantly exacerbate disease activity clinically and pathologically in the recipient mice.<br><br>CONCLUSION: Our results revealed a distinct gut microbiome signature in VKH patients and showed an exacerbating effect of this gut microbiome on experimental autoimmune uveitis (EAU). We also developed two microbial marker profiles in differentiating VKH patients from healthy controls as well as predicting the effectiveness of treatment.}, }
@article {pmid31927754, year = {2020}, author = {Picciariello, A and Papagni, V and De Fazio, M and Martines, G and Memeo, R and Vitarelli, A and Dibra, R and Altomare, DF}, title = {Functional outcome and quality of life evaluation of graciloplasty for the treatment of complex recto-vaginal and recto-urethral fistulas.}, journal = {Updates in surgery}, volume = {72}, number = {1}, pages = {205-211}, pmid = {31927754}, issn = {2038-3312}, mesh = {Female ; Humans ; Male ; *Fistula/physiopathology/surgery ; Patient Satisfaction ; Quality of Life ; Recovery of Function ; *Rectal Diseases/physiopathology/surgery ; Surveys and Questionnaires ; Treatment Outcome ; *Urethral Diseases/physiopathology/surgery ; *Urinary Fistula/physiopathology/surgery ; *Urogenital Surgical Procedures/methods ; *Vaginal Diseases/physiopathology/surgery ; }, abstract = {Recto-vaginal (RVF) and recto-urethral (RUF) fistulas are infrequent but disabling conditions that severely affect patients' quality of life. Considering the high recurrence rate after conservative approaches, the best surgical treatment is still challenging. The aim of this study was to evaluate the outcome of graciloplasty to treat patients with complex RVF or RUF, and to investigate its effect on the quality of life. Fourteen patients with RVF and RUF who underwent graciloplasty between 2003 and 2017 were retrospectively enrolled. The main outcome was the healing rate of fistulas. Postoperative patients satisfaction was evaluated administering the Clinical Patient Grading Assessment Scale (CPGAS), SF-36 questionnaires and Changes in Sexual Functioning (CSF) questionnaires. The Wexner score was calculated in case of preoperative faecal incontinence. RVF and RUF were iatrogenic in 11 patients and due to Crohn's disease in 3 cases. After 1 year of follow-up (IQR 10-14 months), the success rate of the procedure was 78%. Out of three patients with RVF due to Crohn's disease, two healed after the procedure. Six months after surgery, all eight SF-36 domains significantly improved except for "body pain"; CSF score significantly increased from 35.5 (IQR 31-38.7) to 44 (IQR 37.7-48.5); CPGAS score improved from a median value of 0 (IQR 0-0) to 4 (IQR 3.2-4). The Wexner score was calculated only in 5 patients with preoperative faecal incontinence and it significantly decreased from a median value of 12 (IQR 11-14) to 5 (IQR 4-5). Graciloplasty could be considered as a first option treatment for complex or recurrent RVF and RUF. It shows a good healing rate even in case of unfavourable factors like Crohn's disease.}, }
@article {pmid31927673, year = {2020}, author = {Song, Y and Himmel, B and Öhrmalm, L and Gyarmati, P}, title = {The Microbiota in Hematologic Malignancies.}, journal = {Current treatment options in oncology}, volume = {21}, number = {1}, pages = {2}, pmid = {31927673}, issn = {1534-6277}, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Bacteremia/diagnosis/etiology/therapy ; Biodiversity ; Combined Modality Therapy ; Disease Management ; Dysbiosis/diagnosis/*etiology/therapy ; Gastrointestinal Microbiome ; Hematologic Neoplasms/*complications/diagnosis/therapy ; Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Humans ; Immunocompromised Host ; Metagenome ; Metagenomics/methods ; *Microbiota ; }, abstract = {There are approximately 1.2 million new hematologic malignancy cases resulting in ~ 690,000 deaths each year worldwide, and hematologic malignancies remain the most commonly occurring cancer in children. Even though advances in anticancer treatment regimens in recent decades have considerably improved survival rates, their cytotoxic effects and the resulting long-term complications pose a significant burden on the patients and the health care system. Therefore, non-toxic treatment modalities are needed to decrease side effects. The human body is the host to approximately 40 trillion microbes, known as the human microbiota. The large majority of the microbiota is located in the gastrointestinal tract, and is primarily composed of bacteria. The microbiota plays several important physiological roles, ranging from digestive functions to immunological and neural development. Investigating the microbiota in patients with hematologic malignancies has several important implications. The microbiota affects hematopoiesis, and influences the efficacies of chemotherapy and antimicrobial treatments. Determination of the microbiota composition and diversity could be an important part of risk stratification in the future, and may also take part to personalize antimicrobial treatments. Modulation of the microbiota via probiotics or fecal transplant can potentially be involved in reducing side effects of chemotherapy, and eliminating multiple drug resistant strains in patients with hematologic malignancies.}, }
@article {pmid31923639, year = {2020}, author = {Cheng, YW and Phelps, E and Nemes, S and Rogers, N and Sagi, S and Bohm, M and El-Halabi, M and Allegretti, JR and Kassam, Z and Xu, H and Fischer, M}, title = {Fecal Microbiota Transplant Decreases Mortality in Patients with Refractory Severe or Fulminant Clostridioides difficile Infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {18}, number = {10}, pages = {2234-2243.e1}, doi = {10.1016/j.cgh.2019.12.029}, pmid = {31923639}, issn = {1542-7714}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile infection (CDI). FMT cures nearly 80% of patients with severe or fulminant CDI (SFCDI) when utilized in a sequential manner. We compared outcomes of hospitalized patients before and after implementation of an FMT program for SFCDI and investigated whether the changes could be directly attributed to the FMT program.<br><br>METHODS: We performed a retrospective analysis of characteristics and outcomes of patients hospitalized for SFCDI (430 hospitalizations) at a single center, from January 2009 through December 2016. We performed subgroup analyses of 199 patients with fulminant CDI and 110 patients with refractory SFCDI (no improvement after 5 or more days of maximal anti-CDI antibiotic therapy). We compared CDI-related mortality within 30 days of hospitalization, CDI-related colectomy, length of hospital stay, and readmission to the hospital within 30 days before (2009-2012) vs after (2013-2016) implementation of the inpatient FMT program.<br><br>RESULTS: CDI-related mortality and colectomy were lower after implementation of the FMT program. Overall, CDI-related mortality was 10.2% before the FMT program was implemented vs 4.4% after (P = .02). For patients with fulminant CDI, CDI-related mortality was 21.3% before the FMT program was implemented vs 9.1% after (P = .015). For patients with refractory SFCDI, CDI-related mortality was 43.2% before the FMT program vs 12.1% after (P < .001). The FMT program significantly reduced CDI-related colectomy in patients with SFCDI (6.8% before vs 2.7% after; P = .041), in patients with fulminant CDI (15.7% before vs 5.5% after; P = .017), and patients with refractory SFCDI (31.8% vs 7.6%; P&#xa0;= .001). The effect of FMT program implementation on CDI-related mortality remained significant for patients with refractory SFCDI after we accounted for the underlying secular trend (odds ratio, 0.09 for level change; P = .023).<br><br>CONCLUSIONS: An FMT program significantly decreased CDI-related mortality among patients hospitalized with refractory SFCDI.}, }
@article {pmid31922003, year = {2020}, author = {Zeng, SL and Li, SZ and Xiao, PT and Cai, YY and Chu, C and Chen, BZ and Li, P and Li, J and Liu, EH}, title = {Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism.}, journal = {Science advances}, volume = {6}, number = {1}, pages = {eaax6208}, pmid = {31922003}, issn = {2375-2548}, mesh = {Amino Acids/drug effects/metabolism ; Animals ; Citrus/chemistry ; Dysbiosis/drug therapy/microbiology/pathology ; Feces/microbiology ; Flavones/chemistry/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Insulin Resistance/genetics ; Metabolic Syndrome/*drug therapy/microbiology/pathology ; Metabolome/drug effects ; Mice ; Obesity/*drug therapy/metabolism/microbiology/pathology ; Prebiotics/microbiology ; }, abstract = {Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)-induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.}, }
@article {pmid31921049, year = {2019}, author = {Li, X and Chu, Q and Huang, Y and Xiao, Y and Song, L and Zhu, S and Kang, Y and Lu, S and Xu, J and Ren, Z}, title = {Consortium of Probiotics Attenuates Colonization of Clostridioides difficile.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2871}, pmid = {31921049}, issn = {1664-302X}, abstract = {Clostridioides difficile infection (CDI) is increasing morbidity and mortality rates globally. Fecal microbiota transplantation (FMT), an effective therapy for eliminating Clostridioides difficile (C. difficile), cannot be used extensive due to a range of challenges. Probiotics thus constitutes a promising alternative therapy. In our study, we evaluated the effect of consortium of probiotics including five Lactobacilli strains and two Bifidobacterium strains on the colonization of toxigenic BI/NAP1/027 C. difficile in a mouse model. The results of 16S rRNA sequencing and targeted metabolomics showed the consortium of probiotics effectively decreased the colonization of C. difficile, changed the α- and β-diversity of the gut microbiota, decreased the primary bile acids, and increased the secondary bile acids. Spearman's correlation showed that some of the OTUs such as Akkermansia, Bacteroides, Blautia et al. were positively correlated with C. difficile numbers and the primary bile acids, and negatively correlated with the secondary bile acids. However, some of the OTUs, such as Butyricicoccus, Ruminococcus, and Rikenellaceae, were negatively correlated with C. difficile copies and the primary bile acids, and positively correlated with the secondary bile acids. In summary, the consortium of probiotics effectively decreases the colonization of C. difficile, probably via alteration of gut microbiota and bile acids. Our probiotics mixture thus offers a promising FMT alternative.}, }
@article {pmid31919742, year = {2020}, author = {Zhang, T and Lu, G and Zhao, Z and Liu, Y and Shen, Q and Li, P and Chen, Y and Yin, H and Wang, H and Marcella, C and Cui, B and Cheng, L and Ji, G and Zhang, F}, title = {Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening.}, journal = {Protein &amp; cell}, volume = {11}, number = {4}, pages = {251-266}, pmid = {31919742}, issn = {1674-8018}, mesh = {Animals ; Centrifugation ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; High-Throughput Nucleotide Sequencing ; Injections, Intraperitoneal ; Male ; Metabolomics ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Suspensions/administration &amp; dosage/metabolism/*pharmacology ; }, abstract = {Fecal microbiota transplantation (FMT) by manual preparation has been applied to treat diseases for thousands of years. However, this method still endures safety risks and challenges the psychological endurance and acceptance of doctors, patients and donors. Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events. This washing preparation makes delivering a precise dose of the enriched microbiota feasible, instead of using the weight of stool. Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted. The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process. Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing. Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washing-process. In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.}, }
@article {pmid31917160, year = {2020}, author = {Zhou, A and Tang, L and Zeng, S and Lei, Y and Yang, S and Tang, B}, title = {Gut microbiota: A new piece in understanding hepatocarcinogenesis.}, journal = {Cancer letters}, volume = {474}, number = {}, pages = {15-22}, doi = {10.1016/j.canlet.2020.01.002}, pmid = {31917160}, issn = {1872-7980}, mesh = {Animals ; Bacteria/*pathogenicity ; Carcinoma, Hepatocellular/epidemiology/microbiology/*pathology ; Dysbiosis/*complications/microbiology ; *Gastrointestinal Microbiome ; Humans ; Liver Neoplasms/epidemiology/microbiology/*pathology ; }, abstract = {The gut microbiota forms a symbiotic relationship with the host and benefits the body in many critical aspects of life. However, immune system defects, alterations in the gut microbiota and environmental changes can destroy this symbiotic relationship and may lead to diseases, including cancer. Due to the anatomic and functional connection of the gut and liver, increasing studies show the important role of the gut microbiota in the carcinogenesis of hepatocellular carcinoma (HCC). In this manuscript, we review the available evidence and analyze some potential mechanisms of the gut microbiota, including bacterial dysbiosis, lipopolysaccharide (LPS), and genotoxins, in the progression and promotion of HCC. Furthermore, we discuss the possible therapeutic applications of probiotics, chemotherapy modulation, immunotherapy, targeted drugs and fecal microbiota transplantation (FMT) in targeting the gut microbiota.}, }
@article {pmid31910984, year = {2020}, author = {Glassner, KL and Abraham, BP and Quigley, EMM}, title = {The microbiome and inflammatory bowel disease.}, journal = {The Journal of allergy and clinical immunology}, volume = {145}, number = {1}, pages = {16-27}, doi = {10.1016/j.jaci.2019.11.003}, pmid = {31910984}, issn = {1097-6825}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; *Colitis, Ulcerative/immunology/microbiology/therapy ; *Crohn Disease/immunology/microbiology/therapy ; Diet ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Humans ; Prebiotics ; Probiotics/therapeutic use ; Risk Factors ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic immune-mediated disease affecting the gastrointestinal tract. IBD consists of 2 subtypes: ulcerative colitis and Crohn disease. IBD is thought to develop as a result of interactions between environmental, microbial, and immune-mediated factors in a genetically susceptible host. Of late, the potential role of the microbiome in the development, progression, and treatment of IBD has been a subject of considerable interest and enquiry. Indeed, studies in human subjects have shown that the gut microbiome is different in patients with IBD compared with that in healthy control subjects. Other evidence in support of a fundamental role for the microbiome in patients with IBD includes identification of mutations in genes involved in microbiome-immune interactions among patients with IBD and epidemiologic observations implicating such microbiota-modulating risk factors as antibiotic use, cigarette smoking, levels of sanitation, and diet in the pathogenesis of IBD. Consequently, there has been much interest in the possible benefits of microbiome-modulating interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and gene manipulation in the treatment of IBD. In this review we will discuss the role of the gut microbiome in patients with IBD; our focus will be on human studies.}, }
@article {pmid31910227, year = {2020}, author = {Lecronier, M and Tashk, P and Tamzali, Y and Tenaillon, O and Denamur, E and Barrou, B and Aron-Wisnewsky, J and Tourret, J}, title = {Gut microbiota composition alterations are associated with the onset of diabetes in kidney transplant recipients.}, journal = {PloS one}, volume = {15}, number = {1}, pages = {e0227373}, pmid = {31910227}, issn = {1932-6203}, mesh = {Akkermansia ; DNA, Bacterial/*genetics ; Diabetes Mellitus, Type 2/complications/metabolism/*microbiology/pathology ; Faecalibacterium prausnitzii/genetics/isolation &amp; purification/metabolism ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Kidney Transplantation/*adverse effects ; Lactobacillus/genetics/isolation &amp; purification/metabolism ; Male ; Middle Aged ; Risk Factors ; Verrucomicrobia/genetics/isolation &amp; purification/metabolism ; }, abstract = {METHODS: Patients transplanted at our institution provided fecal samples before, and 3-9 months after KT. Fecal bacterial DNA was extracted and 9 bacteria or bacterial groups were quantified by qPCR.<br><br>RESULTS: 50 patients (19 controls without diabetes, 15 who developed New Onset Diabetes After Transplantation, NODAT, and 16 with type 2 diabetes before KT) were included. Before KT, Lactobacillus sp. tended to be less frequently detected in controls than in those who would become diabetic following KT (NODAT) and in initially diabetic patients (60%, 87.5%, and 100%, respectively, p = 0.08). The relative abundance of Faecalibacterium prausnitzii was 30 times lower in initially diabetic patients than in controls (p = 0.002). The relative abundance of F. prausnitzii of NODAT patients was statistically indistinguishable from controls and from diabetic patients. The relative abundance of Lactobacillus sp. increased following KT in NODAT and in initially diabetic patients (20-fold, p = 0.06, and 25-fold, p = 0.02, respectively). In contrast, the proportion of Akkermansia muciniphila decreased following KT in NODAT and in initially diabetic patients (2,500-fold, p = 0.04, and 50,000-fold, p<0.0001, respectively). The proportion of Lactobacillus and A. muciniphila did not change in controls between before and after the transplantation. Consequently, after KT the relative abundance of Lactobacillus sp. was 25 times higher (p = 0.07) and the relative abundance of A. muciniphila was 2,000 times lower (p = 0.002) in diabetics than in controls.<br><br>CONCLUSION: An alteration of the gut microbiota composition involving Lactobacillus sp., A. muciniphila and F. prausnitzii is associated with the glycemic status in KT recipients, raising the question of their role in the genesis of NODAT.}, }
@article {pmid31907459, year = {2020}, author = {Zhai, B and Ola, M and Rolling, T and Tosini, NL and Joshowitz, S and Littmann, ER and Amoretti, LA and Fontana, E and Wright, RJ and Miranda, E and Veelken, CA and Morjaria, SM and Peled, JU and van den Brink, MRM and Babady, NE and Butler, G and Taur, Y and Hohl, TM}, title = {High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis.}, journal = {Nature medicine}, volume = {26}, number = {1}, pages = {59-64}, pmid = {31907459}, issn = {1546-170X}, support = {R01 AI139632/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI093808/AI/NIAID NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; R37 AI093808/AI/NIAID NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; }, mesh = {Bacteria/isolation &amp; purification ; Candida/pathogenicity ; Candidiasis, Invasive/*microbiology ; Cross Infection/blood/microbiology ; Feces/microbiology ; Hematopoietic Stem Cell Transplantation ; Humans ; Intestines/*microbiology ; *Mycobiome ; Species Specificity ; Transplantation, Homologous ; }, abstract = {The intestinal microbiota is a complex community of bacteria, archaea, viruses, protists and fungi[1,2]. Although the composition of bacterial constituents has been linked to immune homeostasis and infectious susceptibility[3-7], the role of non-bacterial constituents and cross-kingdom microbial interactions in these processes is poorly understood[2,8]. Fungi represent a major cause of infectious morbidity and mortality in immunocompromised individuals, although the relationship of intestinal fungi (that is, the mycobiota) with fungal bloodstream infections remains undefined[9]. We integrated an optimized bioinformatics pipeline with high-resolution mycobiota sequencing and comparative genomic analyses of fecal and blood specimens from recipients of allogeneic hematopoietic cell transplant. Patients with Candida bloodstream infection experienced a prior marked intestinal expansion of pathogenic Candida species; this expansion consisted of a complex dynamic between multiple species and subspecies with a stochastic translocation pattern into the bloodstream. The intestinal expansion of pathogenic Candida spp. was associated with a substantial loss in bacterial burden and diversity, particularly in the anaerobes. Thus, simultaneous analysis of intestinal fungi and bacteria identifies dysbiosis states across kingdoms that may promote fungal translocation and facilitate invasive disease. These findings support microbiota-driven approaches to identify patients at risk of fungal bloodstream infections for pre-emptive therapeutic intervention.}, }
@article {pmid31905350, year = {2020}, author = {Settanni, CR and Ianiro, G and Franceschi, F and Gasbarrini, G and Gasbarrini, A}, title = {From Regular Catharsis with Castor Oil to Recognizing the Importance of the Intestinal Microbiota.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {}, number = {}, pages = {1-9}, doi = {10.1159/000505395}, pmid = {31905350}, issn = {1421-9875}, abstract = {The need to shed light on the unknown aspects of pathophysiology of common disorders, such as gastrointestinal ones, has led researchers through last decades to study and define the role of microorganisms within the human intestine and their interactions with the host. The progress of technology has permitted the overcoming of culture-based methods to study microbes and paved the way to molecular techniques, which allow the analysis of microbial genome, microbial functions, and metabolism. These progresses opened a window on the world of microbiology and permitted to deepen into the key role played by gut microbiota and dysbiosis in health status and diseases, both gastrointestinal and extraintestinal. So, scientists focused their attention in developing new strategies to restore eubiosis and to manipulate gut microbes by modifying dietary habits, administrating antibiotics, probiotics, and prebiotics and using fecal microbiota transplantation as treatment of gastrointestinal, infectious, cardiovascular, metabolic, immune-mediated, neuro-psychiatric, and oncological disorders. The next challenges will be to elaborate standard protocols with definite outcomes predictors in disease-specific settings.}, }
@article {pmid31901867, year = {2020}, author = {Sarrabayrouse, G and Landolfi, S and Pozuelo, M and Willamil, J and Varela, E and Clark, A and Campos, D and Herrera, C and Santiago, A and Machiels, K and Vermeire, S and Martí, M and Espin, E and Manichanh, C}, title = {Mucosal microbial load in Crohn's disease: A potential predictor of response to faecal microbiota transplantation.}, journal = {EBioMedicine}, volume = {51}, number = {}, pages = {102611}, pmid = {31901867}, issn = {2352-3964}, mesh = {Animals ; Crohn Disease/*microbiology/pathology ; Cytokines/metabolism ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Inflammation/microbiology/pathology ; Intestinal Mucosa/*microbiology/pathology ; Mice ; Models, Biological ; Reproducibility of Results ; }, abstract = {BACKGROUND: The remission of Crohn's disease (CD) can be accomplished by faecal microbiota transplantation (FMT). However, this procedure has a low success rate, which could be attributed to mis-communication between recipient intestinal mucosa and donor microbiota.<br><br>METHODS: Here we used a human explant tissue model and an in vivo mouse model to examine changes in recipient intestinal mucosa upon contact with a faecal suspension (FS) obtained from a healthy donor. CD patients provided resected inflamed and non-inflamed mucosal tissues, whereas control colonic mucosa samples were collected from colorectal cancer patients. For the models, mucosal microbiome composition and tissue response were evaluated.<br><br>FINDINGS: We show that cytokine release and tissue damage were significantly greater in inflamed compared to non-inflamed CD tissues. Moreover, mucosal samples harbouring an initial low microbial load presented a shift in composition towards that of the FS, an increase in the relative count of Faecalibacterium prausnitzii, and a higher secretion of anti-inflammatory cytokine IL-10 compared to those with a high microbial load.<br><br>INTERPRETATION: Our results indicate that FMT during active inflammatory disease can compromise treatment outcome. We recommend the stratification of FMT recipients on the basis of tissue microbial load as a strategy to ensure successful colonization.<br><br>FUNDING: This study was supported by grants from the Instituto de Salud Carlos III/FEDER (PI17/00614), the European Commission: (INCOMED-267128) and PERIS (SLT002/16). K.M. is a postdoctoral fellow and S.V. a senior clinical investigator of the Fund for Scientific Research Flanders, Belgium (FWO-Vlaanderen).}, }
@article {pmid31900292, year = {2020}, author = {Ding, N and Zhang, X and Zhang, XD and Jing, J and Liu, SS and Mu, YP and Peng, LL and Yan, YJ and Xiao, GM and Bi, XY and Chen, H and Li, FH and Yao, B and Zhao, AZ}, title = {Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes.}, journal = {Gut}, volume = {69}, number = {9}, pages = {1608-1619}, pmid = {31900292}, issn = {1468-3288}, mesh = {Animals ; Bacteroides/*isolation &amp; purification ; Correlation of Data ; Cytokines/analysis ; Diet, High-Fat/*adverse effects ; *Dysbiosis/etiology/microbiology ; Endotoxemia/microbiology ; Epididymis/immunology/pathology ; Feces/microbiology ; Gastrointestinal Microbiome/immunology ; Humans ; Macrophages/immunology ; Male ; Mice ; Prevotella/*isolation &amp; purification ; Sperm Motility/*immunology ; Spermatogenesis/*immunology ; T-Lymphocytes/immunology ; }, abstract = {OBJECTIVE: High-fat diet (HFD)-induced metabolic disorders can lead to impaired sperm production. We aim to investigate if HFD-induced gut microbiota dysbiosis can functionally influence spermatogenesis and sperm motility.<br><br>DESIGN: Faecal microbes derived from the HFD-fed or normal diet (ND)-fed male mice were transplanted to the mice maintained on ND. The gut microbes, sperm count and motility were analysed. Human faecal/semen/blood samples were collected to assess microbiota, sperm quality and endotoxin.<br><br>RESULTS: Transplantation of the HFD gut microbes into the ND-maintained (HFD-FMT) mice resulted in a significant decrease in spermatogenesis and sperm motility, whereas similar transplantation with the microbes from the ND-fed mice failed to do so. Analysis of the microbiota showed a profound increase in genus Bacteroides and Prevotella, both of which likely contributed to the metabolic endotoxaemia in the HFD-FMT mice. Interestingly, the gut microbes from clinical subjects revealed a strong negative correlation between the abundance of Bacteroides-Prevotella and sperm motility, and a positive correlation between blood endotoxin and Bacteroides abundance. Transplantation with HFD microbes also led to intestinal infiltration of T cells and macrophages as well as a significant increase of pro-inflammatory cytokines in the epididymis, suggesting that epididymal inflammation have likely contributed to the impairment of sperm motility. RNA-sequencing revealed significant reduction in the expression of those genes involved in gamete meiosis and testicular mitochondrial functions in the HFD-FMT mice.<br><br>CONCLUSION: We revealed an intimate linkage between HFD-induced microbiota dysbiosis and defect in spermatogenesis with elevated endotoxin, dysregulation of testicular gene expression and localised epididymal inflammation as the potential causes.<br><br>TRIAL REGISTRATION NUMBER: NCT03634644.}, }
@article {pmid31900289, year = {2020}, author = {Chen, X and Li, P and Liu, M and Zheng, H and He, Y and Chen, MX and Tang, W and Yue, X and Huang, Y and Zhuang, L and Wang, Z and Zhong, M and Ke, G and Hu, H and Feng, Y and Chen, Y and Yu, Y and Zhou, H and Huang, L}, title = {Gut dysbiosis induces the development of pre-eclampsia through bacterial translocation.}, journal = {Gut}, volume = {69}, number = {3}, pages = {513-522}, doi = {10.1136/gutjnl-2019-319101}, pmid = {31900289}, issn = {1468-3288}, mesh = {Animals ; *Bacterial Translocation ; Blood Pressure ; CD4 Lymphocyte Count ; Case-Control Studies ; Chemokines/genetics ; Creatinine/blood ; Cytokines/genetics ; Disease Models, Animal ; Dysbiosis/*complications/physiopathology ; Faecalibacterium ; Feces/microbiology ; Female ; Fetal Resorption/microbiology ; Fusobacteria ; *Gastrointestinal Microbiome ; Humans ; Intestine, Small/immunology ; Mice ; Placenta/*immunology/metabolism/*microbiology ; Pre-Eclampsia/*microbiology/physiopathology ; Pregnancy ; Proteinuria/urine ; RNA, Messenger/metabolism ; T-Lymphocytes, Regulatory ; Th17 Cells ; Veillonella ; }, abstract = {OBJECTIVE: Pre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis of PE remains unknown.<br><br>DESIGN: We performed a case-control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation.<br><br>RESULTS: Patients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly Fusobacterium and Veillonella, were enriched, whereas beneficial bacteria, including Faecalibacterium and Akkermansia, were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria, Fusobacterium, and inflammatory cytokine levels were significantly increased.<br><br>CONCLUSIONS: This study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.}, }
@article {pmid31898677, year = {2019}, author = {Sasidharan, BK and Ramadass, B and Viswanathan, PN and Samuel, P and Gowri, M and Pugazhendhi, S and Ramakrishna, BS}, title = {A phase 2 randomized controlled trial of oral resistant starch supplements in the prevention of acute radiation proctitis in patients treated for cervical cancer.}, journal = {Journal of cancer research and therapeutics}, volume = {15}, number = {6}, pages = {1383-1391}, doi = {10.4103/jcrt.JCRT_152_19}, pmid = {31898677}, issn = {1998-4138}, mesh = {Acute Disease ; Administration, Oral ; *Dietary Supplements ; Fatty Acids/analysis ; Feces/chemistry ; Female ; Humans ; Incidence ; Neoplasm Staging ; Proctitis/*etiology/*prevention &amp; control ; Radiation Injuries/*etiology/*prevention &amp; control ; Radiotherapy/adverse effects ; Starch/*administration &amp; dosage ; Uterine Cervical Neoplasms/*complications/diagnosis/radiotherapy ; }, abstract = {BACKGROUND: Radiation induced proctitis is frequently encountered during the radiation therapy of cervical and prostate cancers that causes pain and occasionally with bleeding and may affect the continuity of radiation therapy.<br><br>AIMS AND OBJECTIVES: The purpose of the study is to look at the benefit of administration of an oral prebiotic amylase resistant starch in reducing the incidence of acute radiation proctitis, a distressing symptom in patients receiving radiation therapy for cancer of the cervix.<br><br>MATERIAL AND METHODS: The study was conducted between 2011 and 2014 in 104 patients receiving radical chemo-radiotherapy for carcinoma cervix. Patients were randomized in to two arms, one receiving 30 gm of resistant starch and the other digestible starch on a daily basis throughout the course of the external radiotherapy. All patients received standard 4-field box radiation portals, 50 Gy in 25 fractions with 4 cycles of weekly concurrent Cisplatin. At completion of external beam radiotherapy, all patients underwent LDR/HDR brachytherapy. The study was double blinded and allocation was concealed from the investigators. The investigator recorded the radiotherapy related toxicity of the patients according to CTC V 3.0. The incidence and severity of grade 2-4 diarrhoea and proctitis were documented on a weekly basis and compared across the two groups and analyzed. Stool short chain fatty acid concentrations were measured at baseline at 2[nd] and 4[th] week and after 6 weeks of completion of radiotherapy in both study placebo arms and reported. The pattern of microbiota in the stool were also estimated in all patients at 4 time points. Two patients who progressed during therapy were not included in the analyses and two patients discontinued the intervention. A per protocol analyses was done.<br><br>RESULTS: At analysis there were 50 patients in each arm. The severity of clinical proctitis was found to be similar in both groups of patients with 12.2 % of patients experiencing toxicity of grade 2 and above in digestible starch group versus 14.6% in the resistant starch group. Functional proctitis was similarly graded and it was found that 16.3 % patients in digestible starch group experienced toxicity against 10.2 % patients in the resistant starch group. This difference was seen at 4[th] week and continued in the subsequent weeks till the end of radiation. Both groups had similar reported toxicity at 6 weeks post intervention and similar incidence of grade 2 and above diarrhea. The resistant starch group was found to have 8% incidence as compared to 2% in the other group at the 5[th] and 6[th] week. The short chain fatty acid concentrations were not significantly different in the groups at any point.<br><br>CONCLUSION: The study did not demonstrate a significant benefit in administering resistant starch over and above normal diet to patients receiving pelvic radiotherapy. The reasons may be attributed to concurrent use of chemotherapy and decrease in intestinal probiotics. The use of digestible starch in the control arm may have contributed to lower incidence of the toxicity endpoints as well.}, }
@article {pmid31898476, year = {2020}, author = {Moura, IB and Normington, C and Ewin, D and Clark, E and Wilcox, MH and Buckley, AM and Chilton, CH}, title = {Method comparison for the direct enumeration of bacterial species using a chemostat model of the human colon.}, journal = {BMC microbiology}, volume = {20}, number = {1}, pages = {2}, pmid = {31898476}, issn = {1471-2180}, support = {Not applicable//Seres Therapeutics/International ; 3R02 _93//Leeds Cares (GB)/International ; A1332//Rosetrees Trust/International ; }, mesh = {Anti-Bacterial Agents/*adverse effects ; Bacteria/*classification/genetics/growth &amp; development/isolation &amp; purification ; Bacteriological Techniques/*methods ; Clindamycin/adverse effects ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/chemically induced/*therapy ; Colon/microbiology ; Fecal Microbiota Transplantation/*adverse effects ; Gastrointestinal Microbiome/drug effects ; Humans ; Microbial Viability ; Models, Biological ; Phylogeny ; Real-Time Polymerase Chain Reaction ; Vancomycin/adverse effects ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) has a high recurrent infection rate. Faecal microbiota transplantation (FMT) has been used successfully to treat recurrent CDI, but much remains unknown about the human gut microbiota response to replacement therapies. In this study, antibiotic-mediated dysbiosis of gut microbiota and bacterial growth dynamics were investigated by two quantitative methods: real-time quantitative PCR (qPCR) and direct culture enumeration, in triple-stage chemostat models of the human colon. Three in vitro models were exposed to clindamycin to induce simulated CDI. All models were treated with vancomycin, and two received an FMT. Populations of total bacteria, Bacteroides spp., Lactobacillus spp., Enterococcus spp., Bifidobacterium spp., C. difficile, and Enterobacteriaceae were monitored using both methods. Total clostridia were monitored by selective culture. Using qPCR analysis, we additionally monitored populations of Prevotella spp., Clostridium coccoides group, and Clostridium leptum group.<br><br>RESULTS: Both methods showed an exacerbation of disruption of the colonic microbiota following vancomycin (and earlier clindamycin) exposure, and a quicker recovery (within 4&#x2009;days) of the bacterial populations in the models that received the FMT. C. difficile proliferation, consistent with CDI, was also observed by both qPCR and culture. Pearson correlation coefficient showed an association between results varying from 98% for Bacteroides spp., to 62% for Enterobacteriaceae.<br><br>CONCLUSIONS: Generally, a good correlation was observed between qPCR and bacterial culture. Overall, the molecular assays offer results in real-time, important for treatment efficacy, and allow the monitoring of additional microbiota groups. However, individual quantification of some genera (e.g. clostridia) might not be possible without selective culture.}, }
@article {pmid31898340, year = {2020}, author = {Li, J and Dubois, W and Thovarai, V and Wu, Z and Feng, X and Peat, T and Zhang, S and Sen, SK and Trinchieri, G and Chen, J and Mock, BA and Young, NS}, title = {Attenuation of immune-mediated bone marrow damage in conventionally housed mice.}, journal = {Molecular carcinogenesis}, volume = {59}, number = {2}, pages = {237-245}, pmid = {31898340}, issn = {1098-2744}, support = {Z01 HL002315/ImNIH/Intramural NIH HHS/United States ; ZIA BC010008/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Anemia, Aplastic/immunology/pathology/*therapy ; Animals ; Bone Marrow/*immunology/pathology ; Bone Marrow Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/*immunology ; Hyaluronan Receptors/immunology/metabolism ; Immunologic Memory/immunology ; Lymphocyte Activation/immunology ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Specific Pathogen-Free Organisms ; T-Lymphocytes/*immunology/metabolism/transplantation ; Transplantation Immunology ; Transplantation, Homologous ; }, abstract = {In humans, bone marrow (BM) failure syndromes, both constitutional and acquired, predispose to myeloid malignancies. We have modeled acquired immune aplastic anemia, the paradigmatic disease of these syndromes, in the mouse by infusing lymph node cells from specific pathogen-free (SPF) CD45.1 congenic C57BL/6 (B6) donors into hybrid CByB6F1 recipients housed either in conventional (CVB) or SPF facilities. The severity of BM damage was reduced in CVB recipients; they also had reduced levels of CD44[+] CD62L[-] effector memory T cells, reduced numbers of donor-type CD44[+] T cells, and reduced expansion of donor-type CD8 T cells carrying T-cell receptor β-variable regions 07, 11, and 17. Analyses of fecal samples through 16S ribosomal RNA amplicon sequencing revealed greater gut microbial alpha diversity in CVB mice relative to that of SPF mice. Thus, the presence of a broader spectrum of gut microorganisms in CVB-housed CByB6F1 could have primed recipient animal's immune system leading to suppression of allogeneic donor T-cell activation and expansion and attenuation of host BM destruction. These results suggest the potential benefit of diverse gut microbiota in patients receiving BM transplants.}, }
@article {pmid31897587, year = {2020}, author = {Wang, Y and Zhang, C and Lai, J and Zhao, Y and Lu, D and Bao, R and Feng, X and Zhang, T and Liu, Z}, title = {Noninvasive PET tracking of post-transplant gut microbiota in living mice.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {47}, number = {4}, pages = {991-1002}, pmid = {31897587}, issn = {1619-7089}, mesh = {Animals ; Anti-Bacterial Agents ; *Gastrointestinal Microbiome ; Mice ; Optical Imaging ; Positron-Emission Tomography ; RNA, Ribosomal, 16S ; }, abstract = {PURPOSE: The role that gut microbiota plays in determining the efficacy of the anti-tumor effect of immune checkpoint inhibitors is gaining increasing attention, and fecal bacterial transplantation has been recognized as a promising strategy for improving or rescuing the effect of immune checkpoint inhibition. However, techniques for the precise monitoring of in vivo bacterial behaviors after transplantation are limited. In this study, we aimed to use metabolic labeling and subsequent positron emission tomography (PET) imaging to track the in vivo behaviors of gut bacteria that are responsible for the efficacy of anti-PD-1 therapy in living mice.<br><br>METHODS: The antitumor effect of anti-PD-1 blockade was tested in a low-response 4T1 syngeneic mouse model with or without fecal transplantation and with or without broad-spectrum antibiotic imipenem treatment. High-throughput sequencing analyses of 16S rRNA gene amplicons in feces of 4T1 tumor-bearing mice pre- and post-anti-PD-1 treatment were performed. The identified bacteria, Bacteroides fragilis (B. fragilis), were labeled with [64]Cu and fluorescence dye by the metabolic labeling of N3 followed by click chemistry. In vivo PET and optical imaging of B. fragilis were performed in mice after oral gavage.<br><br>RESULTS: The disturbance of gut microbiota reduced the efficacy of anti-PD-1 treatment, and the combination of B. fragilis gavage and PD-1 blockade was beneficial in rescuing the antitumor effect of anti-PD-1 therapy. Metabolic oligosaccharide engineering and biorthogonal click chemistry resulted in successful B. fragilis labeling with [64]Cu and fluorescence dye with high in vitro and in vivo stability and no effect on viability. PET imaging successfully detected the in vivo behaviors of B. fragilis after transplantation.<br><br>CONCLUSION: PET tracking by metabolic labeling is a powerful, noninvasive tool for the real-time tracking and quantitative imaging of gut microbiota. This strategy is clinically translatable and may also be extended to the PET tracking of other functional cells to guide cell-based adoptive therapies.}, }
@article {pmid31896938, year = {2019}, author = {Pierrard, J and Seront, E}, title = {Impact of the gut microbiome on immune checkpoint inhibitor efficacy-a systematic review.}, journal = {Current oncology (Toronto, Ont.)}, volume = {26}, number = {6}, pages = {395-403}, pmid = {31896938}, issn = {1718-7729}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antineoplastic Agents, Immunological/*therapeutic use ; *Gastrointestinal Microbiome ; Humans ; Neoplasms/*drug therapy/*microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Immune checkpoint inhibitors (icis) are increasingly being used in clinical practice, improving outcomes for cancer patients. Preclinical models showed significant interaction between the gut microbiome (gm) and response to icis. However, that interaction remains unclear in clinical practice.<br><br>METHODS: We performed a systematic review in medline to determine&#x25a0; whether antibiotics affect ici efficacy,&#x25a0; whether baseline gm composition and ici efficacy show any correlations,&#x25a0; whether baseline gm composition and emergence of immune-related adverse events (iraes) show any correlations, and&#x25a0; whether gm manipulation can alleviate the iraes.Included publications had to be written in English or French and had to describe a quantifiable link between gm composition or its modification and the response to icis or the occurrence of iraes, or both.<br><br>RESULTS: Of 1451 articles published before December 2018, 13 publications met the inclusion criteria. Five full-text articles and two abstracts highlighted a negative effect of antibiotics on ici efficacy. The composition of the gm was associated with ici efficacy in five full-text articles and one abstract, and with iraes in two full-text articles. In 2 cases, fecal microbiota transplantation was reported to reduce immune colitis.<br><br>CONCLUSIONS: If possible, antibiotics should be avoided before ici treatment because of their negative effect on ici anticancer efficacy. No specific commensal bacterium was associated with ici efficacy, but an intact gm with high bacterial diversity and a good ratio of "responder-associated" bacteria to "non-responder-associated" bacteria seem to be correlated with better patient outcomes. Fecal microbiota transplantation is a promising technique for reducing ici-associated colitis.}, }
@article {pmid31896581, year = {2020}, author = {Todt, D and Friesland, M and Moeller, N and Praditya, D and Kinast, V and Brüggemann, Y and Knegendorf, L and Burkard, T and Steinmann, J and Burm, R and Verhoye, L and Wahid, A and Meister, TL and Engelmann, M and Pfankuche, VM and Puff, C and Vondran, FWR and Baumgärtner, W and Meuleman, P and Behrendt, P and Steinmann, E}, title = {Robust hepatitis E virus infection and transcriptional response in human hepatocytes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {3}, pages = {1731-1741}, pmid = {31896581}, issn = {1091-6490}, mesh = {Animals ; Antiviral Agents/pharmacology ; Carcinoma, Hepatocellular ; Cell Culture Techniques ; Cell Line, Tumor ; Genotype ; Hep G2 Cells ; Hepatitis E/*metabolism/virology ; Hepatitis E virus/drug effects/*genetics/*physiology ; Hepatocytes/*virology ; Humans ; Liver Neoplasms/drug therapy ; Mice ; RNA-Dependent RNA Polymerase/genetics/metabolism ; Replicon ; Ribavirin/metabolism ; Swine ; Viral Load ; Virus Replication ; }, abstract = {Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and the leading cause for acute viral hepatitis worldwide. The virus is classified as a member of the genus Orthohepevirus A within the Hepeviridae family. Due to the absence of a robust cell culture model for HEV infection, the analysis of the viral life cycle, the development of effective antivirals and a vaccine is severely limited. In this study, we established a protocol based on the HEV genotype 3 p6 (Kernow C-1) and the human hepatoma cell lines HepG2 and HepG2/C3A with different media conditions to produce intracellular HEV cell culture-derived particles (HEVcc) with viral titers between 10[5] and 10[6] FFU/mL. Viral titers could be further enhanced by an HEV variant harboring a mutation in the RNA-dependent RNA polymerase. These HEVcc particles were characterized in density gradients and allowed the trans-complementation of subgenomic reporter HEV replicons. In addition, in vitro produced intracellular-derived particles were infectious in liver-humanized mice with high RNA copy numbers detectable in serum and feces. Efficient infection of primary human and swine hepatocytes using the developed protocol could be observed and was inhibited by ribavirin. Finally, RNA sequencing studies of HEV-infected primary human hepatocytes demonstrated a temporally structured transcriptional defense response. In conclusion, this robust cell culture model of HEV infection provides a powerful tool for studying viral-host interactions that should facilitate the discovery of antiviral drugs for this important zoonotic pathogen.}, }
@article {pmid31888470, year = {2019}, author = {Goloshchapov, OV and Olekhnovich, EI and Sidorenko, SV and Moiseev, IS and Kucher, MA and Fedorov, DE and Pavlenko, AV and Manolov, AI and Gostev, VV and Veselovsky, VA and Klimina, KM and Kostryukova, ES and Bakin, EA and Shvetcov, AN and Gumbatova, ED and Klementeva, RV and Shcherbakov, AA and Gorchakova, MV and Egozcue, JJ and Pawlowsky-Glahn, V and Suvorova, MA and Chukhlovin, AB and Govorun, VM and Ilina, EN and Afanasyev, BV}, title = {Long-term impact of fecal transplantation in healthy volunteers.}, journal = {BMC microbiology}, volume = {19}, number = {1}, pages = {312}, pmid = {31888470}, issn = {1471-2180}, mesh = {Adult ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Time Factors ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been recently approved by FDA for the treatment of refractory recurrent clostridial colitis (rCDI). Success of FTM in treatment of rCDI led to a number of studies investigating the effectiveness of its application in the other gastrointestinal diseases. However, in the majority of studies the effects of FMT were evaluated on the patients with initially altered microbiota. The aim of our study was to estimate effects of FMT on the gut microbiota composition in healthy volunteers and to monitor its long-term outcomes.<br><br>RESULTS: We have performed a combined analysis of three healthy volunteers before and after capsule FMT by evaluating their general condition, adverse clinical effects, changes of basic laboratory parameters, and several immune markers. Intestinal microbiota samples were evaluated by 16S rRNA gene and shotgun sequencing. The data analysis demonstrated profound shift towards the donor microbiota taxonomic composition in all volunteers. Following FMT, all the volunteers exhibited gut colonization with donor gut bacteria and persistence of this effect for almost &#x223c;1 year of observation. Transient changes of immune parameters were consistent with suppression of T-cell cytotoxicity. FMT was well tolerated with mild gastrointestinal adverse events, however, one volunteer developed a systemic inflammatory response syndrome.<br><br>CONCLUSIONS: The FMT leads to significant long-term changes of the gut microbiota in healthy volunteers with the shift towards donor microbiota composition and represents a relatively safe procedure to the recipients without long-term adverse events.}, }
@article {pmid31887116, year = {2019}, author = {Hantschel, J and Weis, S and Schäfer, KH and Menger, MD and Kohl, M and Egert, M and Laschke, MW}, title = {Effect of endometriosis on the fecal bacteriota composition of mice during the acute phase of lesion formation.}, journal = {PloS one}, volume = {14}, number = {12}, pages = {e0226835}, pmid = {31887116}, issn = {1932-6203}, mesh = {Animals ; Disease Models, Animal ; Dysbiosis ; Endometriosis/*microbiology/pathology ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/genetics ; Green Fluorescent Proteins ; Mice ; Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Accumulating evidence indicates that there is an interaction between the gut microbiota and endometriotic lesions. The new formation of these lesions is associated with stem cell recruitment, angiogenesis and inflammation, which may affect the composition of the gut microbiota. To test this hypothesis, we herein induced endometriotic lesions by transplantation of uterine tissue fragments from green fluorescent protein (GFP)+ donor mice into the peritoneal cavity of GFP- C57BL/6 wild-type mice. Sham-transplanted animals served as controls. Fecal pellets of the animals were collected 3 days before as well as 7 and 21 days after the induction of endometriosis to analyze the composition of the gut microbiota by means of 16S ribosomal RNA gene sequencing. The transplantation of uterine tissue fragments resulted in the establishment of endometriotic lesions in all analyzed mice. These lesions exhibited a typical histomorphology with endometrial glands surrounded by a vascularized stroma. Due to their bright GFP signal, they could be easily differentiated from the surrounding GFP- host tissue. Bacterial 16S rRNA genes were successfully PCR-amplified from the DNA extracts of all obtained mice fecal samples. However, no significant effect of endometriosis induction on the composition of the bacterial microbiota was detected with our experimental setup. Our findings allow careful speculation that endometriosis in mice does not induce pronounced dysbiosis during the acute phase of lesion formation.}, }
@article {pmid31886921, year = {2020}, author = {Schepper, JD and Collins, F and Rios-Arce, ND and Kang, HJ and Schaefer, L and Gardinier, JD and Raghuvanshi, R and Quinn, RA and Britton, R and Parameswaran, N and McCabe, LR}, title = {Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {35}, number = {4}, pages = {801-820}, doi = {10.1002/jbmr.3947}, pmid = {31886921}, issn = {1523-4681}, support = {R01 AT007695/AT/NCCIH NIH HHS/United States ; R01 DK101050/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bone Density ; *Gastrointestinal Microbiome ; Glucocorticoids/toxicity ; Male ; Mice ; Osteoblasts ; *Osteoporosis/chemically induced/drug therapy ; }, abstract = {Glucocorticoids (GCs) are potent immune-modulating drugs with significant side effects, including glucocorticoid-induced osteoporosis (GIO). GCs directly induce osteoblast and osteocyte apoptosis but also alter intestinal microbiota composition. Although the gut microbiota is known to contribute to the regulation of bone density, its role in GIO has never been examined. To test this, male C57/Bl6J mice were treated for 8 weeks with GC (prednisolone, GC-Tx) in the presence or absence of broad-spectrum antibiotic treatment (ABX) to deplete the microbiota. Long-term ABX prevented GC-Tx-induced trabecular bone loss, showing the requirement of gut microbiota for GIO. Treatment of GC-Tx mice with a probiotic (Lactobacillus reuteri [LR]) prevented trabecular bone loss. Microbiota analyses indicated that GC-Tx changed the abundance of Verrucomicobiales and Bacteriodales phyla and random forest analyses indicated significant differences in abundance of Porphyromonadaceae and Clostridiales operational taxonomic units (OTUs) between groups. Furthermore, transplantation of GC-Tx mouse fecal material into recipient naïve, untreated WT mice caused bone loss, supporting a functional role for microbiota in GIO. We also report that GC caused intestinal barrier breaks, as evidenced by increased serum endotoxin level (2.4-fold), that were prevented by LR and ABX treatments. Enhancement of barrier function with a mucus supplement prevented both GC-Tx-induced barrier leakage and trabecular GIO. In bone, treatment with ABX, LR or a mucus supplement reduced GC-Tx-induced osteoblast and osteocyte apoptosis. GC-Tx suppression of Wnt10b in bone was restored by the LR and high-molecular-weight polymer (MDY) treatments as well as microbiota depletion. Finally, we identified that bone-specific Wnt10b overexpression prevented GIO. Taken together, our data highlight the previously unappreciated involvement of the gut microbiota and intestinal barrier function in trabecular GIO pathogenesis (including Wnt10b suppression and osteoblast and osteocyte apoptosis) and identify the gut as a novel therapeutic target for preventing GIO. © 2019 American Society for Bone and Mineral Research.}, }
@article {pmid31886629, year = {2020}, author = {Garcia-Arranz, M and Garcia-Olmo, D and Herreros, MD and Gracia-Solana, J and Guadalajara, H and de la Portilla, F and Baixauli, J and Garcia-Garcia, J and Ramirez, JM and Sanchez-Guijo, F and Prosper, F and , }, title = {Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up.}, journal = {Stem cells translational medicine}, volume = {9}, number = {3}, pages = {295-301}, pmid = {31886629}, issn = {2157-6580}, mesh = {Adipose Tissue/*physiopathology ; Female ; Follow-Up Studies ; Humans ; Male ; Mesenchymal Stem Cell Transplantation/*methods ; Middle Aged ; Rectal Fistula/physiopathology/*therapy ; }, abstract = {The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose-derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single-blind clinical trial, recruiting 57 patients. Forty-four patients were categorized as belonging to the intent-to-treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re-epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long-term and sustained fistula healing.}, }
@article {pmid31886425, year = {2020}, author = {Silva, MDRA and Melo, GB and Malta, FM and Abdala, E and Costa, SF and Pierrotti, LC and Gonçalves, EMN and Castilho, VLP and Chieffi, PP and Gryschek, RCB and Paula, FM}, title = {Subtypes of Blastocystis sp. isolated in fecal samples from transplant candidates in São Paulo, Brazil.}, journal = {Parasite epidemiology and control}, volume = {8}, number = {}, pages = {e00128}, pmid = {31886425}, issn = {2405-6731}, abstract = {Blastocystis sp. is an intestinal protozoan commonly found in fecal samples of many animal species, including humans, but poorly studied in transplant candidates. The aim of this study was to evaluate the occurrence and molecular identification of Blastocystis sp. in fecal samples from transplant candidates. A polymerase chain reaction was performed using specific primers for Blastocystis ribosomal DNA. The DNA sequences obtained were aligned and compared with other sequences from the GenBank and MLST databases. The analyzed samples showed a positivity of 16% (24 of 150) for Blastocystis sp. The highest occurrence was observed in renal transplant candidates (31.4%), followed by hepatic transplant candidates (10.4%) and candidates for bone marrow transplantation (5.9%). Subtype (ST) 3 (45.8%) was the most prevalent among the isolates, followed by ST1 (37.5%), ST2 (12.5%), and ST7 (4.2%). This is the first study of molecular identification Blastocystis sp. in transplant candidates. Our results confirmed that ST3 was the most common subtype in transplant candidates and reinforce the importance of new studies to investigate of Blastocystis sp. in these patients.}, }
@article {pmid31885549, year = {2019}, author = {Wang, Y and Zheng, F and Liu, S and Luo, H}, title = {Research Progress in Fecal Microbiota Transplantation as Treatment for Irritable Bowel Syndrome.}, journal = {Gastroenterology research and practice}, volume = {2019}, number = {}, pages = {9759138}, pmid = {31885549}, issn = {1687-6121}, abstract = {Irritable bowel syndrome is a functional disorder characterized by abdominal pain or discomfort associated with altered bowel habits. Due to the uncertainty of the pathogenesis of IBS and the diversity of its clinical manifestations, IBS cannot be completely cured. Increasing evidence suggests the key role of altered intestinal microbiota in the pathogenesis of IBS. Therefore, attention is being shifted to adjusting the changes in intestinal microbiota to control IBS symptoms. Fecal microbiota transplantation (FMT), antibiotics, probiotics, and synbiotics are currently often employed as treatment for IBS. And FMT is the most significant therapeutic efficacy with the least number of side effects. FMT provides a creative way to restore the abnormal gut microbiome in patients with IBS. But although current clinical studies confirm the effectiveness of FMT in the treatment of IBS, they are short-term studies of small samples, and there is still a lack of large-scale long-term studies. In this paper, we review the intestinal microbiota changes of IBS, the common methods of treating IBS with intestinal microbes, and the research status of FMT for the treatment of IBS. Finally, we put forward some opinions on the future research direction of FMT treatment of IBS.}, }
@article {pmid31884204, year = {2020}, author = {Nagasaka, M and Sexton, R and Alhasan, R and Rahman, S and Azmi, AS and Sukari, A}, title = {Gut microbiome and response to checkpoint inhibitors in non-small cell lung cancer-A review.}, journal = {Critical reviews in oncology/hematology}, volume = {145}, number = {}, pages = {102841}, doi = {10.1016/j.critrevonc.2019.102841}, pmid = {31884204}, issn = {1879-0461}, mesh = {*Carcinoma, Non-Small-Cell Lung/drug therapy/microbiology ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Lung Neoplasms/drug therapy/microbiology ; *Microbiota ; *Molecular Targeted Therapy ; }, abstract = {The gut microbiome is a collection of diverse bacteria that normally reside within the gastrointestinal tract. In recent years, the relationship between the gut microbiome, and fluctuations in it, and overall health has been an intense area of interest in medical research. In addition to having a barrier role in the gastrointestinal tract, there appears to be an immune function of gut microbiota, with a correlation between dysbiosis of gut microbiota and certain inflammatory and malignant disease states of the gastrointestinal system. We have also seen evidence that the gut microbiome can impact response to immunotherapy in melanoma patients. Evidence has also emerged to show that the lung has a microbiome of its own. In this review we will explore the relationship between the gut and lung microbiomes, known as the gut-lung axis, and the potential effects of this axis on anticancer therapy in lung cancer, including checkpoint inhibitors.}, }
@article {pmid31883938, year = {2020}, author = {Reigadas, E and Bouza, E and Olmedo, M and Vázquez-Cuesta, S and Villar-Gómara, L and Alcalá, L and Marín, M and Rodríguez-Fernández, S and Valerio, M and Muñoz, P}, title = {Faecal microbiota transplantation for recurrent Clostridioides difficile infection: experience with lyophilized oral capsules.}, journal = {The Journal of hospital infection}, volume = {105}, number = {2}, pages = {319-324}, doi = {10.1016/j.jhin.2019.12.022}, pmid = {31883938}, issn = {1532-2939}, mesh = {Administration, Oral ; Aged ; Aged, 80 and over ; Capsules/*therapeutic use ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces ; Female ; *Freeze Drying ; Hospitals, Teaching ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective approach for refractory and recurrent Clostridioides difficile infection (CDI). Despite its excellent efficacy, FMT is not yet a routine procedure in most centres. There is very little experience with FMT based on lyophilized capsules, and data from European institutions are lacking. This article describes our experience with FMT to treat recurrent CDI using lyophilized oral capsules.<br><br>METHODS: A prospectively recorded single-centre case series of patients with recurrent CDI who underwent FMT between January 2018 and May 2019 were analysed. The primary outcome was defined as resolution of CDI without recurrences over a two-month period. Overall resolution was defined as resolution of diarrhoea without recurrence of CDI within two months after a further cycle of FMT. The FMT process involved oral ingestion of four or five lyophilized capsules in a single dose. All stool donors were rigorously screened.<br><br>FINDINGS: FMT was performed in 32 patients. Primary cure was achieved in 81.3% of patients, and the overall cure rate was 87.5%. FMT via lyophilized capsules was well tolerated. No FMT procedure-related adverse events and no further complications were observed for lyophilized-capsule FMT.<br><br>CONCLUSIONS: This initial clinical experience suggests that FMT based on oral lyophilized preparations is a safe, well-tolerated, and highly effective treatment for recurrent CDI. Administration of oral lyophilized capsules seems feasible in hospital routine and will enable FMT to be more widely used.}, }
@article {pmid31883108, year = {2020}, author = {Robles-Vera, I and Toral, M and de la Visitación, N and Sánchez, M and Gómez-Guzmán, M and Muñoz, R and Algieri, F and Vezza, T and Jiménez, R and Gálvez, J and Romero, M and Redondo, JM and Duarte, J}, title = {Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects.}, journal = {British journal of pharmacology}, volume = {177}, number = {9}, pages = {2006-2023}, pmid = {31883108}, issn = {1476-5381}, support = {//Fondo Europeo de Desarrollo Regional FEDER/International ; SAF2017-84894-R//Comisi&#xf3;n Interministerial de Ciencia y Tecnolog&#xed;a, Ministerio de Econom&#xed;a y competitividad/International ; SAF2014-55523-R//Comisi&#xf3;n Interministerial de Ciencia y Tecnolog&#xed;a, Ministerio de Econom&#xed;a y competitividad/International ; AGL2015-67995-C3//Comisi&#xf3;n Interministerial de Ciencia y Tecnolog&#xed;a, Ministerio de Econom&#xed;a y competitividad/International ; AGL2015-67995-C3-3-R//Comisi&#xf3;n Interministerial de Ciencia y Tecnolog&#xed;a, Ministerio de Econom&#xed;a y competitividad/International ; CIBER-CV//Ministerio de Economia y Competitividad, Instituto de Salud Carlos III/International ; CIBER-EHD//Ministerio de Economia y Competitividad, Instituto de Salud Carlos III/International ; P12-CTS-2722//Junta de Andaluc&#xed;a/International ; AGR-6826//Junta de Andaluc&#xed;a/International ; CTS-164//Junta de Andaluc&#xed;a/International ; }, mesh = {Animals ; Antihypertensive Agents/pharmacology ; Blood Pressure ; *Gastrointestinal Microbiome ; *Hypertension/drug therapy ; Losartan/pharmacology ; RNA, Ribosomal, 16S ; Rats ; Rats, Inbred SHR ; }, abstract = {BACKGROUND AND PURPOSE: Hypertension is associated with gut dysbiosis. Here we have evaluated the effects of the angiotensin receptor antagonist losartan on gut microbiota in spontaneously hypertensive rats (SHR) to assess their contribution to its antihypertensive effects.<br><br>EXPERIMENTAL APPROACH: Twenty-week-old Wistar Kyoto rats (WKY) and SHR were treated with losartan for 5 weeks (SHR-losartan). Faecal microbiota transplantation (FMT) was performed from donor SHR-losartan group to recipient untreated-SHR. Blood pressure (BP) was measured using tail-cuff plethysmography. Composition of the gut microbiota was assessed by amplification of the V3-V4 region of 16S rRNA gene. T cells were analysed in gut/aorta by flow cytometry.<br><br>KEY RESULTS: Faeces from SHR showed gut dysbiosis, characterised by higher Firmicutes/Bacteroidetes ratios, lower acetate- and higher lactate-producing bacteria, and lower levels of strict anaerobic bacteria, effects which were restored to normal by losartan. Improvement of gut dysbiosis was linked to higher colonic integrity and lower sympathetic drive in the gut. In contrast, hydralazine reduced BP, but it neither restored gut dysbiosis nor colonic integrity. FMT from SHR-losartan to SHR reduced BP, improved the aortic endothelium-dependent relaxation to ACh, and reduced NADPH oxidase activity. These vascular changes were accompanied by both increased Treg and decreased Th17 cell populations in the vascular wall.<br><br>CONCLUSION AND IMPLICATIONS: In SHR, losartan treatment reduced gut dysbiosis and sympathetic drive in the gut, thus improving gut integrity. The changes induced by losartan in gut microbiota contributed, in part, to protecting the vasculature and reducing BP, possibly by modulating the immune system in the gut.}, }
@article {pmid31880660, year = {2020}, author = {}, title = {Addendum for: Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection and Other Conditions in Children: A Joint Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {70}, number = {3}, pages = {404}, doi = {10.1097/MPG.0000000000002601}, pmid = {31880660}, issn = {1536-4801}, mesh = {Child ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; *Gastroenterology ; Humans ; Nutritional Status ; Societies, Medical ; United States ; }, }
@article {pmid31879393, year = {2019}, author = {Ichikawa, M and Sujino, T and Kanai, T}, title = {[The Relationship between Gut Microbiome, Immune System, and Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {12}, pages = {1807-1813}, pmid = {31879393}, issn = {0385-0684}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immune System ; }, abstract = {Various microbes having been living in our intestine and forming the gut microbiome. When dysbiosis which is typically characterized by reduced microbial diversity occurs, many types of diseases are triggered in our bodies. Recently, relationship between gut microbiome and our immune function are discovered gradually. From this view point, the gut microbiome may have an influence on cancer medicine such as development, therapy(immune checkpoint blockade or chemotherapy), and therapeutic toxicity. In real clinical practice, this influence is reported in some cases such as colorectal cancer and other malignancies. In the near future, the approach from gut microbiome may be a clue to improve the existent cancer diagnosis and therapy. In addition, the modulation of gut microbiome in itself, for example fecal microbiota transplant(FMT), probiotics, and limited usage of antibiotics, is expected to be hints for cancer medicine, though this is not yet established and further studies are needed.}, }
@article {pmid31877418, year = {2020}, author = {Johnsen, PH and Hilpüsch, F and Valle, PC and Goll, R}, title = {The effect of fecal microbiota transplantation on IBS related quality of life and fatigue in moderate to severe non-constipated irritable bowel: Secondary endpoints of a double blind, randomized, placebo-controlled trial.}, journal = {EBioMedicine}, volume = {51}, number = {}, pages = {102562}, pmid = {31877418}, issn = {2352-3964}, mesh = {Adult ; Comorbidity ; *Fatigue ; *Fecal Microbiota Transplantation ; Female ; Humans ; Irritable Bowel Syndrome/diagnosis/*epidemiology/*therapy ; Male ; Middle Aged ; Odds Ratio ; *Quality of Life ; Severity of Illness Index ; Surveys and Questionnaires ; Treatment Outcome ; }, abstract = {BACKGROUND: Severity in irritable bowel syndrome (IBS) is associated to impaired quality of life and fatigue. Fecal microbiota transplantation (FMT) induces significant relief in gastro-intestinal related complaints. The objective was to evaluate the effect of FMT on the secondary endpoints: IBS-related quality of life and fatigue in patients with non-constipated IBS.<br><br>METHOD: In this double-blind randomized placebo-controlled, parallel-group, single-center study, we enrolled patients with non-constipated IBS, defined by the ROME 3 criteria. We randomly assigned participants (2:1) in blocks of six to active or placebo FMT. Responder in fatigue and quality of life were defined as a decrease of 20 points in total Fatigue Impact Scale score, and improvement of 14 points in the IBS-quality of life questionnaire, respectively. In a modified-intention-to-treat population, we excluded participants who did not undergo treatment or who were diagnosed with any other disease by pinch biopsies during the treatment procedure.<br><br>FINDINGS: Between Jan1, and Oct 30, 2015, we recruited 90 participants and randomly assigned them to active treatment (n&#xa0;=&#xa0;60) or placebo (n&#xa0;=&#xa0;30). Three participants did not undergo FMT and four were excluded after diagnosis of microscopic colitis, leaving 83 for final modified intention-to-treat analysis (55 in the active treatment group and 28 in the placebo group). Significant improvement in QoL (Odds ratio (OR) 3,801; confidence interval (CI)&#xa0;=&#xa0;1,309-11,042 p&#xa0;=&#xa0;0.011) and fatigue (OR&#xa0;=&#xa0;4,398; CI&#xa0;=&#xa0;1,175-16,468 and p&#xa0;=&#xa0;0,020) was found at six months. Absence of other self reported functional disorders and presence of depression at baseline is suggested to predict a lasting effect of FMT in QoL and fatigue, respectively.<br><br>INTERPRETATION: FMT induced significant relief in quality of life and fatigue. Results suggest a lasting effect of FMT in subgroups that should be further investigated in future studies. Funding Helse Nord, Norway and the Norwegian Centre of Rural Medicine, University of Troms&#xf8;, Norway.}, }
@article {pmid31876898, year = {2020}, author = {Harkins, CP and Kong, HH and Segre, JA}, title = {Manipulating the Human Microbiome to Manage Disease.}, journal = {JAMA}, volume = {323}, number = {4}, pages = {303-304}, doi = {10.1001/jama.2019.19602}, pmid = {31876898}, issn = {1538-3598}, mesh = {Child ; Child Nutrition Disorders/diet therapy/microbiology ; Clostridium Infections/therapy ; *Disease Management ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; HIV Infections/drug therapy ; Humans ; Infant, Newborn ; *Microbiota ; Neonatal Sepsis/prevention &amp; control ; Vagina/microbiology ; }, }
@article {pmid31876732, year = {2019}, author = {Wei, Y and Li, N and Xing, H and Guo, T and Gong, H and Chen, D}, title = {Effectiveness of fecal microbiota transplantation for severe diarrhea after drug-induced hypersensitivity syndrome.}, journal = {Medicine}, volume = {98}, number = {52}, pages = {e18476}, pmid = {31876732}, issn = {1536-5964}, mesh = {Acute Disease ; Adult ; Diarrhea/etiology/*therapy ; Drug Hypersensitivity Syndrome/*complications ; *Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; Intestine, Small/diagnostic imaging ; Multiple Organ Failure/diagnostic imaging/etiology/therapy ; RNA, Ribosomal, 16S/genetics ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {The aim of this study was to assess effectiveness of fecal microbiota transplantation (FMT) in treating intestinal failure associated with drug-induced hypersensitivity syndrome (DIHS).A 32-year-old Chinese woman, who developed DIHS-associated multiple organ dysfunction syndrome (MODS) manifesting as combined dysfunction of the intestine, liver, and kidney, was treated with 4 times of FMT at a frequency of once every 6 days. The structure and composition of the patient's fecal microbiota were analyzed by 16S rRNA-based molecular techniques. The clinical outcomes after FMT treatment were assessed by abdominal contrast-enhanced computed tomography (CT), characterization of fecal microbiota, measurement of serum inflammatory markers, and other clinical examinations.After 4 rounds of FMT were administered, the patient showed dramatic improvement in MODS and severe diarrhea with these clinical conditions under control. We consistently observed significant alteration in her gut microbiota, mainly involving considerable enrichment in Firmicutes members and depletion of Proteobacteria opportunistic organisms. Moreover, this reconstituted bacterial community composition correlated with fecal output, T helper cells, and inflammatory markers. Abdominal contrast-enhanced CT scans before and after FMT indicated significant improvement in inflammation and edema within the small intestine and colon of the patient. Notably, after completion of the fourth FMT, the level of inflammation in the intestine and colon had returned to normal. Over 6 months of follow-up, the intestinal mucous remained normal.Our results represent a breakthrough in the clinical management of MODS and suggest new therapeutic avenues to pursue for microbiota-related indications.}, }
@article {pmid31875601, year = {2020}, author = {Caner, A and Zorbozan, O and Tunalı, V and Kantar, M and Aydoğdu, S and Aksoylar, S and Gürüz, Y and Turgay, N}, title = {Intestinal Protozoan Parasitic Infections in Immunocompromised Child Patients with Diarrhea.}, journal = {Japanese journal of infectious diseases}, volume = {73}, number = {3}, pages = {187-192}, doi = {10.7883/yoken.JJID.2019.054}, pmid = {31875601}, issn = {1884-2836}, mesh = {Adolescent ; Child ; Child, Preschool ; Cross-Sectional Studies ; Diarrhea/epidemiology/*parasitology ; Feces/parasitology ; Female ; Humans ; *Immunocompromised Host ; Intestinal Diseases, Parasitic/*diagnosis/*epidemiology ; Male ; Prevalence ; Turkey/epidemiology ; }, abstract = {Intestinal protozoan parasites are common causes of infectious diarrhea in children receiving anticancer therapy or undergoing transplantation. Additionally, immunosuppression therapy in such patients may exacerbate the symptoms related to these parasitic infections. The aim of this study was to evaluate the prevalence and diagnostic importance of parasitic protozoan infections in children treated for malignancies or undergoing transplantation, and to highlight the control of intestinal parasitic infections for immunosuppressed patients at a hospital in İzmir, Turkey. In total, 82 stool samples from 62 patients were analyzed by microscopic examination and polymerase chain reaction (PCR) for the presence of coccidian parasites. Our results showed that Cryptosporidium, Cyclospora, and Cystoisospora were present in 22.5% (14/62), 9.6% (6/62), and 3.2% (2/62) of the cases using either method, respectively. The prevalence of these coccidian parasites identified with both methods was 35.4% (20/62). Other intestinal parasites (Blastocystis, Giardia, and Entamoeba coli) were detected in 10 patients. PCR analysis showed the presence of all coccidian parasites in the same stool sample for one patient. Finally, both PCR and microscopic examination of the stools revealed that there is a higher prevalence of Cryptosporidium, Cyclospora, and Cystoisospora in immunocompromised children. These examinations allowed an early start of appropriate antibiotic treatments and led to an increased percentage of correctly treated patients.}, }
@article {pmid31875037, year = {2019}, author = {Heimesaat, MM and Mrazek, K and Bereswill, S}, title = {Murine fecal microbiota transplantation lowers gastrointestinal pathogen loads and dampens pro-inflammatory immune responses in Campylobacter jejuni infected secondary abiotic mice.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {19797}, pmid = {31875037}, issn = {2045-2322}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Apoptosis ; Bacterial Load ; Campylobacter Infections/*immunology ; Campylobacter jejuni ; Colon/*microbiology/pathology ; Epithelium/metabolism ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Immune System ; Inflammation ; Male ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; }, abstract = {Conventional mice are protected from Campylobacter jejuni infection by the murine host-specific gut microbiota composition. We here addressed whether peroral fecal microbiota transplantation (FMT) might be an antibiotics-independent option to lower even high gastrointestinal C. jejuni loads in the infected vertebrate host. To address this, secondary abiotic mice were generated by broad-spectrum antibiotic treatment and perorally infected with C. jejuni by gavage. One week later, mice were stably colonized with more than 10[9] C. jejuni and subjected to peroral FMT from murine donors on three consecutive days. Two weeks post-intervention, gastrointestinal C. jejuni loads were up to 7.5 orders of magnitude lower following murine FMT versus mock challenge. Remarkably, FMT reversed C. jejuni induced colonic epithelial apoptosis, but enhanced proliferative and regenerative responses in the colon thereby counteracting pathogenic cell damage. Furthermore, FMT dampened both, innate and adaptive immune cell responses in the large intestines upon C. jejuni infection that were accompanied by less C. jejuni-induced colonic nitric oxide secretion. Our study provides strong evidence that novel probiotic formulations developed as alternative option to FMT in severe intestinal inflammatory morbidities including Clostridoides difficile infection might be effective to treat campylobacteriosis and lower pathogen loads in colonized vertebrates including farm animals.}, }
@article {pmid31873192, year = {2020}, author = {Hill, C}, title = {Balancing the risks and rewards of live biotherapeutics.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {17}, number = {3}, pages = {133-134}, pmid = {31873192}, issn = {1759-5053}, mesh = {*Bacteremia ; Escherichia coli ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Reward ; }, }
@article {pmid31872304, year = {2019}, author = {Ocansey, DKW and Wang, L and Wang, J and Yan, Y and Qian, H and Zhang, X and Xu, W and Mao, F}, title = {Mesenchymal stem cell-gut microbiota interaction in the repair of inflammatory bowel disease: an enhanced therapeutic effect.}, journal = {Clinical and translational medicine}, volume = {8}, number = {1}, pages = {31}, pmid = {31872304}, issn = {2001-1326}, support = {81670502//the National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Several investigations affirm that, patients with inflammatory bowel disease (IBD) exhibit dysbiosis characterized by restricted biodiversity and imbalanced bacterial composition intertwined with immune dysregulation. The interaction between stem cells and gut microbiota is a novel and highly promising field that could add up to a better understanding of the gut physiology, as well as therapeutic improvement towards diseases like IBD. Through direct contact or release of products and/or metabolites, gut bacteria regulate gut homeostasis, damage repair, regeneration and differentiation of stem cells. In the same way, mesenchymal stem cells (MSCs) produce similar effects including restoration of gut-microbiome composition. BODY: We reviewed the anti-inflammatory, antimicrobial, pathogenic bacterial clearance, proliferation and tissue remodeling effects of mesenchymal stem cells (MSCs) and fecal microbiota transplantation (FMT) as separate transplants in IBD, and the outcome of the interaction between MSCs and gut microbiota.<br><br>CONCLUSION: The two therapies share several points of connection in therapeutics with enhanced functionalities in their interaction with each other. Focused investigations of MSC-gut bacteria interactions could lead to a novel discovery in therapeutics. We also anticipate an improved clinical remission rate in a combined FMT-MSC transplantation approach in IBD than the current single FMT or MSC approach.}, }
@article {pmid31870137, year = {2019}, author = {Woldeamlak, B and Yirdaw, K and Biadgo, B}, title = {Role of Gut Microbiota in Type 2 Diabetes Mellitus and Its Complications: Novel Insights and Potential Intervention Strategies.}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {74}, number = {6}, pages = {314-320}, doi = {10.4166/kjg.2019.74.6.314}, pmid = {31870137}, issn = {2233-6869}, mesh = {Diabetes Mellitus, Type 2/epidemiology/*pathology ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestines/microbiology ; Prebiotics ; Probiotics ; Risk Factors ; }, abstract = {Type 2 diabetes mellitus has become one of the fastest growing public health problems worldwide. The disease is believed to involve a complex process involving genetic susceptibility and environmental factors. The human intestine harbors hundreds of trillions of bacteria, as well as bacteriophage particles, viruses, fungi, and archaea, which constitute a complex and dynamic ecosystem referred to as the gut microbiota. Increasing evidence has indicated changes in the gut microbiota composition or function in type 2 diabetic patients. An analysis of 'dysbiosis' enables the detection of alterations in the specific bacteria, clusters of bacteria, or bacterial functions associated with the occurrence of type 2 diabetes. These bacteria are involved predominantly in the control of inflammation and energy homeostasis. This review attempts to show that the gut microbiota are important factors for the occurrence of type 2 diabetes and are important for the treatment of gut microbiota dysbiosis through bariatric surgery, fecal microbiota transplantation, prebiotics, and probiotics.}, }
@article {pmid31862370, year = {2020}, author = {Yan, T and Nian, T and Liao, Z and Xiao, F and Wu, B and Bi, K and He, B and Jia, Y}, title = {Antidepressant effects of a polysaccharide from okra (Abelmoschus esculentus (L) Moench) by anti-inflammation and rebalancing the gut microbiota.}, journal = {International journal of biological macromolecules}, volume = {144}, number = {}, pages = {427-440}, doi = {10.1016/j.ijbiomac.2019.12.138}, pmid = {31862370}, issn = {1879-0003}, mesh = {Abelmoschus/*chemistry ; Animals ; Anti-Inflammatory Agents/chemistry/*pharmacology ; Antidepressive Agents/chemistry/*pharmacology ; Cell Line ; Gastrointestinal Microbiome/*drug effects ; Inflammation/chemically induced/drug therapy/metabolism/pathology ; Lipopolysaccharides/toxicity ; MAP Kinase Signaling System/drug effects ; Male ; Mice ; Polysaccharides/chemistry/*pharmacology ; }, abstract = {The present study aimed to evaluate the antidepressant-like effect of a polysaccharide (OP), which is isolated from okra (Abelmoschus esculentus (L) Moench), in CUMS-induced mice and its possible mechanisms. OPT, FST and TST were employed to examine the anxiety and depressive behavior in CUMS-induced mice and fecal microbiota transplantation (FMT) CUMS-induced mice, while proinflammatory cytokines, TLR4/NF-κB pathway and MAPKs signaling were detected in both CUMS-induced mice and LPS-induced BV2 cells. The results showed that anxiety- and depressive-like behaviors, gut microbiota dysbiosis and changes of SCFAs, and activation of inflammatory reactions in the colon, serum, and hippocampus of CUMS-induced mice, as well as activation of inflammatory reactions in BV2 cells, could be alleviated by the treatment of OP. The mice that were colonized by OP microbiota showed improved anxiety and depressive behaviors and lower inflammatory response. Furthermore, OP inhibited the expression of TLR4, the nuclear translocation of NF-κB and high levels of proinflammatory cytokines, and enhanced the MAPKs signaling, these effects of OP also observed in LPS-induced BV2 cells. Above all, suggested that the potential mechanism of the antidepressant-like effects of OP was closely correlated with the bidirectional communication of microbiota-gut-brain axis via regulation of inflammation response.}, }
@article {pmid31859812, year = {2019}, author = {Lara, A and Espadín, C}, title = {[Considerations should be taken into account to avoid complexities in the transplantation of fecal microbiota.].}, journal = {Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia}, volume = {36}, number = {5}, pages = {674}, doi = {10.4067/S0716-10182019000500674}, pmid = {31859812}, issn = {0717-6341}, mesh = {*Clostridium Infections ; Colonoscopy ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; Universities ; }, }
@article {pmid31859781, year = {2019}, author = {Quera, R and Sedano, R and Espinoza, R and Rivera, D}, title = {[Transplantation of fecal matter in octogenarian patients with recurrent Clostridioides difficile infection].}, journal = {Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia}, volume = {36}, number = {4}, pages = {536-540}, doi = {10.4067/S0716-10182019000400536}, pmid = {31859781}, issn = {0717-6341}, mesh = {Aged, 80 and over ; Clostridium Infections/*therapy ; Diarrhea/*microbiology ; *Fecal Microbiota Transplantation ; Female ; Humans ; Recurrence ; }, abstract = {Clostridioides (formerly Clostridium) difficile infection has become a major health problem due to the increase in its incidence, severity, and recurrence. In this last scenario, age over 65 has been associated with a more unfavorable evolution. Risk factors such as the presence of altered immunity, comorbidities, malnutrition, polypharmacy, and changes in the intestinal microbiota would explain this higher risk in this group of patients. On the other hand, fecal microbiota transplantation (FMT) is an effective strategy in the treatment of recurrent Clostridioides difficile infection when standard therapy fails. Recently published guidelines suggest that this strategy can be used from the second recurrence. However, few studies have evaluated the results of the FMT in patients over 65 years old, and for our knowledge, there is limited national experience in this group of patients. We present two cases of TMF in octogenarian patients with a recurrent infection due to Clostridioides difficile, with satisfactory recovery at the long term.}, }
@article {pmid31858856, year = {2020}, author = {Hoffmann-Vold, AM and Fretheim, H and Didriksen, H and Molberg, &#xd8;}, title = {The potential of fecal microbiota transplantation in systemic sclerosis.}, journal = {Expert review of clinical immunology}, volume = {16}, number = {2}, pages = {117-118}, doi = {10.1080/1744666X.2019.1707665}, pmid = {31858856}, issn = {1744-8409}, mesh = {Animals ; Dysbiosis/immunology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Gene-Environment Interaction ; Humans ; Scleroderma, Systemic/immunology/*therapy ; }, }
@article {pmid31858698, year = {2020}, author = {Liwinski, T and Elinav, E}, title = {Harnessing the microbiota for therapeutic purposes.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {20}, number = {6}, pages = {1482-1488}, doi = {10.1111/ajt.15753}, pmid = {31858698}, issn = {1600-6143}, mesh = {Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Precision Medicine ; *Probiotics/therapeutic use ; }, abstract = {The myriads of microorganisms colonizing the human host (microbiome) affect virtually every aspect of its physiology in health and disease. The past decade witnessed unprecedented advances in microbiome research. The field rapidly transitioned from descriptive studies to deep mechanistic insights into host-microbiome interactions. This offers the opportunity for microbiome-targeted therapeutic manipulation. Currently, several strategies of microbiome-targeted interventions are intensively explored. Best evidence from human randomized clinical trials is available for fecal microbiota transplantation (FMT). However, patient eligibility as well as long-term efficacy and safety are not sufficiently defined. Therefore, there is currently no officially approved indication for FMT. Probiotics (live microorganisms) have long been discussed as a means to aid human health but have yielded varying results. Emerging techniques utilizing microbiota-targeted diets, small microbial molecules, recombinant bacteriophages, and precise control of strain abundance recently yielded promising results but require further investigation. The rapid technological progress of "omics" tools spurs advances in personalized medicine. Understanding and integration of interindividual microbiome variability holds potential to promote personalized preventive and therapeutic approaches. Emerging evidence points towards the microbiome as an important player having an impact on transplantation outcomes. Microbiome-targeted interventions have potential to aid against the many challenges faced by transplant recipients.}, }
@article {pmid31857899, year = {2019}, author = {Orr, MR and Kocurek, KM and Bakos, YJ and McDowell, RC}, title = {A restoration ecology perspective on the treatment of inflammatory bowel disease.}, journal = {Evolution, medicine, and public health}, volume = {2019}, number = {1}, pages = {217-220}, pmid = {31857899}, issn = {2050-6201}, abstract = {The human gut can be considered an ecosystem comprised of a community of microbes and nonliving components such as food metabolites and food additives. Chronic diseases are increasingly associated with disruption of this ecosystem. The science of restoration ecology was developed to restore degraded ecosystems, but its principles have not been applied widely to gut medicine, including the treatment of inflammatory bowel disease (IBD). One principle of ecological restoration is that 'passive' restoration, which involves removing an ecosystem disturbance, should occur before attempting additional 'active' interventions. We discuss evidence that poor diet is principle source of disturbance in IBD, and therefore requires better attention in its research and clinical care. Another restoration principle is that higher biodiversity may improve ecosystem behavior, but this idea has not been tested for its possible importance in donor stool during fecal microbiota transplants. Lay summary: In patients with chronic disease the gut microbiome behaves like a disturbed ecosystem. Principles borrowed from the science of restoration ecology identify a need to better understand the influence of diet on treatment of inflammatory bowel disease and the importance of donor diversity in fecal microbiota transplants.}, }
@article {pmid31857577, year = {2019}, author = {Cao, Z and Wang, X and Pang, Y and Cheng, S and Liu, J}, title = {Biointerfacial self-assembly generates lipid membrane coated bacteria for enhanced oral delivery and treatment.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {5783}, pmid = {31857577}, issn = {2041-1723}, mesh = {Administration, Oral ; Animals ; Colitis/chemically induced/microbiology/*therapy ; Colon/microbiology/pathology ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Drug Compounding/methods ; Drug Delivery Systems/*methods ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/microbiology/pathology ; *Membrane Lipids ; Mice ; Probiotics/*administration &amp; dosage ; Proof of Concept Study ; }, abstract = {The gut microbiota represents a huge community of microorganisms that play essential roles in immune modulation and homeostasis maintenance. Microbiota transplantation is an important approach to prevent and treat disease as it can inhibit pathogen colonization and positively modulate bacterial composition. However, the development of oral bacterial therapeutics has been restricted by low bioavailability and limited retention in the gastrointestinal tract. Here, we report a simple yet highly efficient method to coat gut microbes via biointerfacial supramolecular self-assembly. Coating can be performed within 15 min by simply vortexing with biocompatible lipids. Bacteria coated with an extra self-assembled lipid membrane exhibit significantly improved survival against environmental assaults and almost unchanged viability and bioactivity. We demonstrate their enhanced efficacies in oral delivery and treatment using two murine models of colitis. We suggest that biointerfacial supramolecular self-assembly may provide a unique platform to generate advanced bacterial therapeutics for the treatment of various diseases.}, }
@article {pmid31853944, year = {2019}, author = {Osadchiy, V and Martin, CR and Mayer, EA}, title = {Gut Microbiome and Modulation of CNS Function.}, journal = {Comprehensive Physiology}, volume = {10}, number = {1}, pages = {57-72}, doi = {10.1002/cphy.c180031}, pmid = {31853944}, issn = {2040-4603}, mesh = {Animals ; Autonomic Nervous System ; Brain/*physiology ; Feeding Behavior ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Motility ; Humans ; Obesity ; }, abstract = {Preclinical evidence strongly suggests a role for the gut microbiome in modulating the host central nervous system function and behavior. Several communication channels have been identified that enable microbial signals to reach the brain and that enable the brain to influence gut microbial composition and function. In rodent models, endocrine, neural, and inflammatory signals generated by gut microbes can alter brain structure and function, while autonomic nervous system activity can affect the microbiome by modulating the intestinal environment and by directly regulating microbial behavior. The amount of information that reaches the brain is dynamically regulated by the blood-brain barrier and the intestinal barrier. In humans, associations between gut microbial composition and function and several brain disorders have been reported, and fecal microbial transplants from patient populations into gnotobiotic mice have resulted in the reproduction of homologous features in the recipient mice. However, in contrast to preclinical findings, there is little information about a causal role of the gut microbiome in modulating human central nervous system function and behavior. Longitudinal studies in large patient populations with therapeutic interventions are required to demonstrate such causality, which will provide the basis for future clinical trials. © 2020 American Physiological Society. Compr Physiol 10:57-72, 2020.}, }
@article {pmid31852769, year = {2020}, author = {El-Salhy, M and Hatlebakk, JG and Gilja, OH and Bråthen Kristoffersen, A and Hausken, T}, title = {Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study.}, journal = {Gut}, volume = {69}, number = {5}, pages = {859-867}, pmid = {31852769}, issn = {1468-3288}, mesh = {Adult ; Donor Selection ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Irritable Bowel Syndrome/microbiology/physiopathology/*therapy ; Male ; Middle Aged ; Patient Satisfaction/*statistics &amp; numerical data ; Prognosis ; Recovery of Function ; Reference Values ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {OBJECTIVE: Faecal microbiota transplantation (FMT) from healthy donors to patients with irritable bowel syndrome (IBS) has been attempted in two previous double-blind, placebo-controlled studies. While one of those studies found improvement of the IBS symptoms, the other found no effect. The present study was conducted to clarify these contradictory findings.<br><br>DESIGN: This randomised, double-blind, placebo-controlled study randomised 165 patients with IBS to placebo (own faeces), 30&#x2009;g FMT or 60&#x2009;g FMT at a ratio of 1:1:1. The material for FMT was obtained from one healthy, well-characterised donor, frozen and administered via gastroscope. The primary outcome was a reduction in the IBS symptoms at 3 months after FMT (response). A response was defined as a decrease of 50 or more points in the total IBS symptom score. The secondary outcome was a reduction in the dysbiosis index (DI) and a change in the intestinal bacterial profile, analysed by 16S rRNA gene sequencing, at 1&#x2009;month following FMT.<br><br>RESULTS: Responses occurred in 23.6%, 76.9% (p<0.0001) and 89.1% (p<00.0001) of the patients who received placebo, 30&#x2009;g FMT and 60&#x2009;g FMT, respectively. These were accompanied by significant improvements in fatigue and the quality of life in patients who received FMT. The intestinal bacterial profiles changed also significantly in the groups received FMT. The FMT adverse events were mild self-limiting gastrointestinal symptoms.<br><br>CONCLUSIONS: FMT is an effective treatment for patients with IBS. Utilising a well-defined donor with a normal DI and favourable specific microbial signature is essential for successful FMT. The response to FMT increases with the dose. Trial registration www.clinicaltrials.gov (NCT03822299) and www.cristin.no (ID657402).}, }
@article {pmid31851851, year = {2020}, author = {Satlin, MJ and Westblade, LF and Lee, JR}, title = {Avoiding infections in transplant recipients: does the gut microbiota have a key role?.}, journal = {Expert review of clinical immunology}, volume = {16}, number = {2}, pages = {113-115}, pmid = {31851851}, issn = {1744-8409}, support = {K23 AI114994/AI/NIAID NIH HHS/United States ; K23 AI124464/AI/NIAID NIH HHS/United States ; }, mesh = {Dysbiosis/etiology/*prevention &amp; control ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; *Organ Transplantation ; Postoperative Complications/*prevention &amp; control ; Transplant Recipients ; }, }
@article {pmid31850583, year = {2020}, author = {Quigley, EMM}, title = {Commentary: faecal microbiota transplantation-from home brew to holy grail.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {51}, number = {1}, pages = {208-209}, doi = {10.1111/apt.15553}, pmid = {31850583}, issn = {1365-2036}, mesh = {*Clostridium Infections ; Colonoscopy ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; Humans ; Vancomycin ; }, }
@article {pmid31850561, year = {2020}, author = {Costello, SP and Bryant, RV}, title = {Editorial: faecal microbiota transplantation-the silver bullet for severe and fulminant Clostridioides difficile infection?.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {51}, number = {1}, pages = {180-181}, doi = {10.1111/apt.15584}, pmid = {31850561}, issn = {1365-2036}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Critical Illness ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid31850117, year = {2019}, author = {Vojvodic, A and Peric-Hajzler, Z and Matovic, D and Vojvodic, P and Vlaskovic-Jovicevic, T and Sijan, G and Dimitrijevic, S and Stepic, N and Wollina, U and Badr, BAE and Badawi, A and Goldust, M and Tirant, M and Nguyen, VT and Fioranelli, M and Lotti, T}, title = {Gut Microbiota and the Alteration of Immune Balance in Skin Diseases: From Nutraceuticals to Fecal Transplantation.}, journal = {Open access Macedonian journal of medical sciences}, volume = {7}, number = {18}, pages = {3034-3038}, pmid = {31850117}, issn = {1857-9655}, abstract = {The P.N.E.I. (Psycho-Neuro-Endocrine-Immunology) approach is represented by the interdisciplinary concept of bidirectional cross-talk between the psycho-neuro-endocrine and immune systems, which can influence the immune response. The well-known Gut-Brain Axis and the Gut-Skin Axis can be merged in a bigger network- the Gut-Brain-Skin Axis, with complex regulation by cytokines, neuro-peptides, neuro-hormones and another messenger (signalling) molecules and maybe the most important modulator of the Gut-Brain-Skin Axis/ the gut microbiota. The role of gut bacterial homeostasis is very important, and the homeostatic imbalance of the immune response may be a relevant etiologic/pathophysiologic factor for extra-intestinal and intestinal inflammatory, allergic and autoimmune diseases. The Low Dose Cytokines Medicine (LDM) is an innovative therapeutic approach. It is based on the most advanced knowledge in molecular biology and low dose pharmacology with the primary outcome. The SKA (Sequential Kinetic Activation) technology, codified and standardised by GUNA S.p.a. -Italy- makes the low doses of signalling molecules able to be active even below the minimum dose classically considered as effective and the significative efficacy of orally administered low-dose signalling molecules is the most representative aspect of LDM. The Physiologic Nutraceuticals and the Low Dose Medicine are two of the most promising approaches for the treatment of skin diseases based on the rebalance of the immune response and the recovery of gut dysbiosis.}, }
@article {pmid31846840, year = {2020}, author = {Xu, J and Song, J and Zhang, Y and Wang, Y and Yang, L and Sha, Y and Sun, B and You, N and Tian, X and Lin, R and Wu, Y}, title = {Jinzhi protects lipopolysaccharide-treated mice against mortality by repairing intestinal mucosal barrier damage and intestinal microecology.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {123}, number = {}, pages = {109749}, doi = {10.1016/j.biopha.2019.109749}, pmid = {31846840}, issn = {1950-6007}, mesh = {Animals ; Caspases/metabolism ; Cytokines/metabolism ; Epithelial Cells/pathology ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Ileum ; Intestinal Mucosa/*drug effects/*pathology ; Intestines/pathology ; Lipopolysaccharides/pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Models, Animal ; Protective Agents/*pharmacology ; RNA, Ribosomal, 16S ; Sepsis/chemically induced ; Survival Rate ; Tight Junction Proteins/metabolism ; }, abstract = {OBJECTIVE: Intestinal mucosal barrier damage is an important mechanism for the development of sepsis and multiple organ dysfunction syndrome. At present, there are no satisfactory and effective methods for the protection of the intestinal mucosal barrier. Jinzhi, the first fecal microbiota transplantation worldwide, is often used to treat critically ill patients; however, the specific mechanism involved in this process remains unclear. The aim of this study was to investigate the therapeutic effect and mechanism of Jinzhi intervention on mice with sepsis induced through treatment with lipopolysaccharide (LPS).<br><br>METHODS: Mice were intraperitoneally injected with LPS to simulate intestinal mucosal barrier function damage in sepsis; intervention was performed through the oral administration of Jinzhi. The effect of Jinzhi on LPS-induced sepsis was analyzed by comparing the vital signs and survival rate of mice under different treatments. Pathological staining and enzyme-linked immunosorbent assay were used to identify the effects of LPS or treatment with Jinzhi on the intestinal mucosal barrier in mice. The effect of LPS or treatment with Jinzhi on the intestinal flora was analyzed via 16S rRNA gene sequencing of ileal contents.<br><br>RESULTS: Immunohistochemistry and enzyme-linked immunosorbent assay showed that treatment with LPS increased levels of inflammatory factors (interleukin-1&#x3b1;, interleukin-6, tumor necrosis factor-&#x3b1;), caspase-3, and caspase-8 in the serum and ileum, and destroyed the tight junction between epithelial cells. Intervention with Jinzhi reduced levels of serum LPS and tumor necrosis factor-&#x3b1;, and repaired the tight junction between epithelial cells. Furthermore, 16S rRNA gene sequencing analysis showed that treatment with Jinzhi improved the diversity and physiological function of the intestinal flora.<br><br>CONCLUSIONS: These results suggest that Jinzhi may be a promising option for the treatment of sepsis caused by LPS, and emphasize that Jinzhi exerts a recovery effect on the imbalance of intestinal flora.}, }
@article {pmid31845054, year = {2020}, author = {Hu, H and Lin, A and Kong, M and Yao, X and Yin, M and Xia, H and Ma, J and Liu, H}, title = {Intestinal microbiome and NAFLD: molecular insights and therapeutic perspectives.}, journal = {Journal of gastroenterology}, volume = {55}, number = {2}, pages = {142-158}, pmid = {31845054}, issn = {1435-5922}, support = {81873098//National Natural Science Foundation of China/ ; 31300716//National Natural Science Foundation of China/ ; 2018ZYYD017//Science and Technology Commission of Hubei Province of China/ ; ZY2019Q003//Health Commission of Hubei Province of China/ ; 2017060201010221//Wuhan Science and Technology Bureau of Hubei Province of China/ ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bile Acids and Salts/metabolism ; Dysbiosis/complications/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/microbiology/physiology ; Non-alcoholic Fatty Liver Disease/*microbiology/*therapy ; Prebiotics ; Probiotics/therapeutic use ; Receptors, Cytoplasmic and Nuclear/*agonists/metabolism ; Signal Transduction ; Synbiotics ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of dysregulated lipid and glucose metabolism, which is often associated with obesity, dyslipidemia and insulin resistance. In view of the high morbidity and health risks of NAFLD, the lack of effective cure has drawn great attention. In recent years, a line of evidence has suggested a close linkage between the intestine and liver diseases such as NAFLD. We summarized the composition and characteristics of intestinal microbes and reviewed molecular insights into the intestinal microbiome in development and progression of NAFLD. Intestinal microbes mainly include bacteria, archaea, viruses and fungi, and the crosstalk between non-bacterial intestinal microbes and human liver diseases should be paid more attention. Intestinal microbiota imbalance may not only increase the intestinal permeability to gut microbes but also lead to liver exposure to harmful substances that promote hepatic lipogenesis and fibrosis. Furthermore, we focused on reviewing the latest "gut-liver axis"-targeting treatment, including the application of antibiotics, probiotics, prebiotics, synbiotics, farnesoid X receptor agonists, bile acid sequestrants, gut-derived hormones, adsorbents and fecal microbiota transplantation for NAFLD. In this review, we also discussed the potential mechanisms of "gut-liver axis" manipulation and efficacy of these therapeutic strategies for NAFLD treatment.}, }
@article {pmid31842339, year = {2019}, author = {Herremans, KM and Riner, AN and Cameron, ME and Trevino, JG}, title = {The Microbiota and Cancer Cachexia.}, journal = {International journal of molecular sciences}, volume = {20}, number = {24}, pages = {}, pmid = {31842339}, issn = {1422-0067}, mesh = {Animals ; Cachexia/diagnosis/*etiology/therapy ; Disease Susceptibility ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Neoplasms/*complications ; Probiotics ; }, abstract = {Cancer cachexia is a multifactorial syndrome defined by weight loss, muscle wasting, and systemic inflammation. It affects the majority of patients with advanced cancer and is associated with poor treatment response, early mortality and decreased quality of life. The microbiota has been implicated in cancer cachexia through pathways of systemic inflammation, gut barrier dysfunction and muscle wasting. The imbalance of the microbiota, known as dysbiosis, has been shown to influence cancer cachexia. Bacteria that play beneficial and detrimental roles in the disease pathogenesis have been identified. The phenotype of cancer cachexia is associated with decreased levels of Lactobacillales and increased levels of Enterobacteriaceae and Parabacteroides. Currently, there are no treatment options that demonstrate increased survival or the quality of life in patients suffering from cancer cachexia. Through the manipulation of beneficial bacteria in the gut microbiota, different treatment options have been explored. Prebiotics and probiotics have been shown to improve outcomes in animal models of cachexia. Expounding on this mechanism, fecal microbiota transplant (FMT) holds promise for a future treatment of cancer cachexia. Further research is necessary to address this detrimental disease process and improve the lives of patients suffering from cancer cachexia.}, }
@article {pmid31839966, year = {2019}, author = {Keller, JJ and Vehreschild, MJ and Hvas, CL and Jørgensen, SM and Kupciskas, J and Link, A and Mulder, CJ and Goldenberg, SD and Arasaradnam, R and Sokol, H and Gasbarrini, A and Hoegenauer, C and Terveer, EM and Kuijper, EJ and Arkkila, P and , }, title = {Stool for fecal microbiota transplantation should be classified as a transplant product and not as a drug.}, journal = {United European gastroenterology journal}, volume = {7}, number = {10}, pages = {1408-1410}, pmid = {31839966}, issn = {2050-6414}, mesh = {Enterocolitis, Pseudomembranous/microbiology/therapy ; *Fecal Microbiota Transplantation/methods/standards ; Feces/*microbiology ; Humans ; Transplants ; }, }
@article {pmid31838936, year = {2019}, author = {Gao, Y and Li, H and Yang, H and Su, J and Huang, L}, title = {The current novel therapeutic regimens for Clostridium difficile infection (CDI) and the potentials of Traditional Chinese Medicine in treatment of CDI.}, journal = {Critical reviews in microbiology}, volume = {45}, number = {5-6}, pages = {729-742}, doi = {10.1080/1040841X.2019.1700905}, pmid = {31838936}, issn = {1549-7828}, mesh = {Animals ; Clostridioides difficile/physiology ; Clostridium Infections/microbiology/*therapy ; Gastrointestinal Microbiome ; Humans ; *Medicine, Chinese Traditional ; }, abstract = {Clostridium difficile infection (CDI) is featured as the dysbiosis of gut microbiota and consequent mild diarrhoea or severe pseudomembranous colitis. However, the frequent recurrence of CDI following treatment course challenged the antibiotic therapy. Currently, to address the relapse of CDI, several novel therapeutic approaches have emerged, including Bezlotoxumab, SYN-004 (Ribaxamase), RBX2660, and faecal microbial transplant. Traditional Chinese Medicine (TCM) is an old medical system accumulated for thousands of years. Orientated by syndrome-based treatment, TCM functions in a multicomponent and multitarget mode. This old medical system showed superiority over conventional medical treatment, particularly in the treatment of complex disorders, including CDI. In the present review, we will elaborate the TCM intervention in the management of CDI and others disorders via restoring the gut microbiota dysbiosis. We hope that this review will deepen our understanding of TCM as an alternative to CDI treatment. However, more rigorously designed basic researches and randomised controlled trials need to conduct to appraise the function mechanisms and effects of TCM. Finally, it is concluded that the combined therapeutic potentials of TCM and western medicine could be harness to resolve the recurrence and improve the outcome of CDI.}, }
@article {pmid31830335, year = {2020}, author = {Hong, AS and Yu, WY and Hong, JM and Cross, CL and Azab, M and Ohning, G and Jayaraj, M}, title = {Proton pump inhibitor in upper gastrointestinal fecal microbiota transplant: A systematic review and analysis.}, journal = {Journal of gastroenterology and hepatology}, volume = {35}, number = {6}, pages = {932-940}, doi = {10.1111/jgh.14958}, pmid = {31830335}, issn = {1440-1746}, mesh = {Clostridium Infections/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Tract/*microbiology ; Humans ; Negative Results ; Proton Pump Inhibitors/*pharmacology ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is used in recurrent Clostridioides difficile infections. However, protocols are facility dependent, and one variable is whether pre-procedural proton pump inhibitors (PPIs) are given. In theory, PPIs reduce acidity and protect the transplanted microbiome for the most potent dose. We conducted a systematic review to study the effect of PPIs on FMT delivered by upper gastrointestinal (GI) routes.<br><br>METHODS: We searched Pubmed/Medline, Cochrane Library, Embase, Scopus, and Web of Science through December 16, 2018 using variations of keywords "fecal microbiota transplant" and "Clostridium difficile infection." Two authors independently reviewed 4210 results and found 11 qualifying studies with data on upper GI FMT, use of PPIs, and the rate of treatment failure at follow-up.<br><br>RESULTS: Of 233 included patients, treatment failure occurred in 20.6% of those with use of PPIs versus 22.6% in the group without (relative risk 0.91; confidence interval 0.56-1.50). Limitations include the lack of studies directly comparing outcomes based on use of PPIs and inability to control for possible confounders such as chronic PPI use, amount of stool transplanted, and pre-FMT antibiotics.<br><br>CONCLUSIONS: We did not find evidence supporting a clinically significant benefit from routine use of PPIs in FMT protocol. It is possible that the theoretical benefit from improved survival of transplanted microbiota is offset by negative effects on the microbiome. We suggest that routine use of PPIs in upper GI FMT be reconsidered. Further investigation is needed to optimize protocols for safety and efficacy.}, }
@article {pmid31828683, year = {2020}, author = {Ebrahimzadeh Leylabadlo, H and Ghotaslou, R and Samadi Kafil, H and Feizabadi, MM and Moaddab, SY and Farajnia, S and Sheykhsaran, E and Sanaie, S and Shanehbandi, D and Bannazadeh Baghi, H}, title = {Non-alcoholic fatty liver diseases: from role of gut microbiota to microbial-based therapies.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {39}, number = {4}, pages = {613-627}, pmid = {31828683}, issn = {1435-4373}, mesh = {Animals ; Disease Progression ; Dysbiosis/complications/microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Mice ; Non-alcoholic Fatty Liver Disease/microbiology/*therapy ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the well-known disease of the liver in adults and children throughout the world. The main manifestations related to NAFLD are an unusual storage of lipid in hepatocytes (hepatic steatosis) and progression of inflammation for non-alcoholic steatohepatitis (NASH). NAFLD is described as a multifactorial complication due to the genetic predisposition, metabolic functions, inflammatory, gut microbiota (GM), and environmental factors. The GM dysregulation among these factors is correlated to NAFLD development. In recent decades, advanced microbial profiling methods are continuing to shed light on the nature of the changes in the GM caused by NASH and NAFLD. In the current review, we aim to perform a literature review in different library databases and electronic searches (Science Direct, PubMed, and Google Scholar) which were randomly obtained. This will be done in order to provide an overview of the relation between GM and NAFLD, and the role of prebiotics, probiotics, and fecal microbiota transplantation (FMT), as potential therapeutic challenges for NAFLD.}, }
@article {pmid31827467, year = {2019}, author = {Quaranta, G and Sanguinetti, M and Masucci, L}, title = {Fecal Microbiota Transplantation: A Potential Tool for Treatment of Human Female Reproductive Tract Diseases.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2653}, pmid = {31827467}, issn = {1664-3224}, mesh = {Endometriosis/therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome ; Genital Diseases, Female/*therapy ; Humans ; Polycystic Ovary Syndrome/therapy ; Uterus/microbiology ; Vagina/microbiology ; Vaginosis, Bacterial/therapy ; }, abstract = {The gastro-intestinal tract is an extensive organ involved in several activities, with a crucial role in immunity. Billions of commensal and transient microorganisms, known as the gut microbiota, and potential pathogens, which are constantly stimulating intestinal immunity, colonize the intestinal epithelial surface. The gut microbiota may be regarded as analogous to a solid organ with multiple different functions. In the last decade, many studies have demonstrated that intestinal bacteria can be a decisive factor in the health-disease balance of the intestine, and they can also be responsible for illnesses in other locations. For this reason, fecal microbiota transplantation (FMT) represents an important therapeutic option for Clostridium difficile infections and hold promise for different clinical conditions, such as multiple sclerosis, autism, obesity, and other systemic diseases. FMT consists of the infusion of a fecal suspension from a healthy donor to a recipient in order to restore gut flora alterations. Similar to the gut, the female reproductive tract is an example of a very complex biological ecosystem. Recent studies indicate a possible relationship between the gut and female tract microbiota, associating specific intestinal bacteria patterns with genital female diseases, such as polycystic ovary syndrome (PCOS), endometriosis and bacterial vaginosis (BV). FMT could represent a potential innovative treatment option in this field.}, }
@article {pmid31824463, year = {2019}, author = {Freitag, TL and Hartikainen, A and Jouhten, H and Sahl, C and Meri, S and Anttila, VJ and Mattila, E and Arkkila, P and Jalanka, J and Satokari, R}, title = {Minor Effect of Antibiotic Pre-treatment on the Engraftment of Donor Microbiota in Fecal Transplantation in Mice.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2685}, pmid = {31824463}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) and is also considered a potential treatment for a wide range of intestinal and systemic diseases. FMT corrects the microbial dysbiosis associated with rCDI, and the engraftment of donor microbiota is likely to play a key role in treatment efficacy. For disease indications other than rCDI, FMT treatment efficacy has been moderate. This may be partly due to stronger resilience of resident host microbiota in patients who do not suffer from rCDI. In rCDI, patients typically have undergone several antibiotic treatments prior to FMT, depleting the microbiota. In this study, we addressed the effect of broad-spectrum antibiotics (Ab) as a pre-treatment to FMT on the engraftment of donor microbiota in recipients. We conducted a pre-clinical study of FMT between two healthy mouse strains, Balb/c as donors and C57BL/6 as recipients, to perform FMT within the same species and to mimic interindividual FMT between human donors and patients. Microbiota composition was assessed with high-throughput 16S rDNA amplicon sequencing. The microbiota of Balb/c and C57BL/6 mice differed significantly, which allowed for the assessment of microbiota transplantation from the donor strain to the recipient. Our results showed that Ab-treatment depleted microbiota in C57BL/6 recipient mice prior to FMT. The diversity of microbiota did not recover spontaneously to baseline levels during 8 weeks after Ab-treatment, but was restored already at 2 weeks in mice receiving FMT. Interestingly, pre-treatment with antibiotics prior to FMT did not increase the overall similarity of the recipient's microbiota to that of the donor's, as compared with mice receiving FMT without Ab-treatment. Pre-treatment with Ab improved the establishment of only a few donor-derived taxa, such as Bifidobacterium, in the recipients, thus having a minor effect on the engraftment of donor microbiota in FMT. In conclusion, pre-treatment with broad-spectrum antibiotics did not improve the overall engraftment of donor microbiota, but did improve the engraftment of specific taxa. These results may inform future therapeutic studies of FMT.}, }
@article {pmid31821445, year = {2020}, author = {Chen, LA}, title = {Intestinal Microbiota Transplantation for Patients With Inflammatory Bowel Disease Prevents Recurrence of C. difficile Infections but Not Recurrence of Gastrointestinal Symptoms.}, journal = {Inflammatory bowel diseases}, volume = {26}, number = {9}, pages = {1421-1422}, pmid = {31821445}, issn = {1536-4844}, support = {K23 DK119544/DK/NIDDK NIH HHS/United States ; }, mesh = {*Clostridioides difficile ; *Clostridium Infections/prevention &amp; control ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy ; }, abstract = {Intestinal microbiota transplantation (IMT) is an effective therapy for recurrent Clostridioides difficile infections in patients with inflammatory bowel disease (IBD). However, further research is needed to understand the safety of this procedure, particularly given the frequency of gastrointestinal symptoms and of IBD treatment escalation after IMT.}, }
@article {pmid31821444, year = {2020}, author = {Tariq, R and Disbrow, MB and Dibaise, JK and Orenstein, R and Saha, S and Solanky, D and Loftus, EV and Pardi, DS and Khanna, S}, title = {Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {26}, number = {9}, pages = {1415-1420}, doi = {10.1093/ibd/izz299}, pmid = {31821444}, issn = {1536-4844}, mesh = {Adult ; Clostridioides difficile ; Colitis/microbiology ; Colitis, Ulcerative/*microbiology ; Crohn Disease/*microbiology ; Diarrhea/microbiology/therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Symptom Flare Up ; Treatment Outcome ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients.<br><br>METHODS: We reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results.<br><br>RESULTS: We included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0-47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3-20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1-51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified.<br><br>CONCLUSIONS: Few patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.}, }
@article {pmid31820774, year = {2020}, author = {Jiang, Y and Liu, Y and Gao, M and Xue, M and Wang, Z and Liang, H}, title = {Nicotinamide riboside alleviates alcohol-induced depression-like behaviours in C57BL/6J mice by altering the intestinal microbiota associated with microglial activation and BDNF expression.}, journal = {Food &amp; function}, volume = {11}, number = {1}, pages = {378-391}, doi = {10.1039/c9fo01780a}, pmid = {31820774}, issn = {2042-650X}, mesh = {Animals ; Brain-Derived Neurotrophic Factor/*metabolism ; Cytokines/metabolism ; Depression/chemically induced/*therapy ; Disease Models, Animal ; Ethanol/*adverse effects ; Gastrointestinal Microbiome/*drug effects ; Hippocampus/cytology/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Microglia/cytology/*drug effects ; Niacinamide/*analogs &amp; derivatives/therapeutic use ; Pyridinium Compounds ; RNA, Ribosomal, 16S ; }, abstract = {The gut microbiota play an important role in many central nervous system diseases through the gut microbiota-brain axis. Recent studies suggest that nicotinamide riboside (NR) has neuroprotective properties. However, it is unknown whether NR can prevent or protect against alcohol-induced depression. Furthermore, it is unclear whether its therapeutic action involves changes in the composition of the gut microbiome. Here, we investigated the effects of NR in the mouse model of alcohol-induced depression. Treatment with NR improved the alcohol-induced depressive behaviour in mice. In addition, NR decreased the number of activated microglia in the hippocampus, and it reduced the levels of pro-inflammatory (IL-1β, IL-6, and TNF-α) and anti-inflammatory (IL-10 and TGF-β) cytokines in the brain of mice with alcohol-induced depression. Furthermore, NR significantly upregulated BDNF and diminished the inhibition of the AKT/GSK3β/β-catenin signalling pathway in the hippocampus of these mice. 16S rRNA sequencing revealed that, compared with control and NR-treated mice, the gut microbiome richness and composition were significantly altered in the depressed mice. Spearman's correlation analysis showed that differential gut bacterial genera correlated with the levels of inflammation-related cytokines and BDNF in the brain. After faecal microbiota transplantation, cognitive behaviours, microglial activity, levels of cytokines and BDNF, and activation state of the AKT/GSK3β/β-catenin signalling pathway (which is downstream of the BDNF receptor, TrkB) in recipient mice were similar to those in donor mice. Collectively, our findings show that NR dietary supplementation protects against alcohol-induced depression-like behaviours, possibly by altering the composition of the gut microbiota.}, }
@article {pmid31820171, year = {2019}, author = {Chavira, A and Belda-Ferre, P and Kosciolek, T and Ali, F and Dorrestein, PC and Knight, R}, title = {The Microbiome and Its Potential for Pharmacology.}, journal = {Handbook of experimental pharmacology}, volume = {260}, number = {}, pages = {301-326}, doi = {10.1007/164_2019_317}, pmid = {31820171}, issn = {0171-2004}, mesh = {Humans ; *Microbiota ; Neoplasms ; Nervous System Diseases ; Obesity ; Pharmaceutical Preparations/metabolism ; *Precision Medicine ; }, abstract = {The human microbiota (the microscopic organisms that inhabit us) and microbiome (their genes) hold considerable potential for improving pharmacological practice. Recent advances in multi-"omics" techniques have dramatically improved our understanding of the constituents of the microbiome and their functions. The implications of this research for human health, including microbiome links to obesity, drug metabolism, neurological diseases, cancer, and many other health conditions, have sparked considerable interest in exploiting the microbiome for targeted therapeutics. Links between microbial pathways and disease states further highlight a rich potential for companion diagnostics and precision medicine approaches. For example, the success of fecal microbiota transplantation to treat Clostridium difficile infection has already started to redefine standard of care with a microbiome-directed therapy. In this review we briefly discuss the nature of human microbial ecosystems and with pathologies and biological processes linked to the microbiome. We then review emerging computational metagenomic, metabolomic, and wet lab techniques researchers are using today to learn about the roles host-microbial interactions have with respect to pharmacological purposes and vice versa. Finally, we describe how drugs affect the microbiome, how the microbiome can impact drug response in different people, and the potential of the microbiome itself as a source of new therapeutics.}, }
@article {pmid31819862, year = {2019}, author = {Niina, A and Kibe, R and Suzuki, R and Yuchi, Y and Teshima, T and Matsumoto, H and Kataoka, Y and Koyama, H}, title = {Improvement in Clinical Symptoms and Fecal Microbiome After Fecal Microbiota Transplantation in a Dog with Inflammatory Bowel Disease.}, journal = {Veterinary medicine (Auckland, N.Z.)}, volume = {10}, number = {}, pages = {197-201}, pmid = {31819862}, issn = {2230-2034}, abstract = {PURPOSE: Recently, fecal microbiota transplantation (FMT) has been tested in veterinary medicine as a treatment option for multiple gastrointestinal (GI) diseases, such as inflammatory bowel disease (IBD). However, there are no reports of changes in the microbial diversity of fecal microbiome after treatment with FMT in canine IBD cases. Moreover, little is known about the long-term efficacy and safety of FMT treatment for dogs. Herein, we present a case of canine intractable IBD treated with repeated, long-term FMT.<br><br>PATIENTS AND METHODS: The patient was a 10-year-old, neutered, male, 4-kg Toy Poodle with a prolonged history of vomiting and diarrhea. Fecal examination for pathogens was negative. Despite treatment with multiple antibacterial and antidiarrheal agents, the patient showed no improvement. Endoscopic mucus sampling diagnosed a case of lymphocytic-plasmacytic duodenitis, ie, idiopathic IBD. Eventually, we performed periodic, long-term fecal microbiota transplantation of fresh donor feces collected from a 4-year-old, 32.8-kg, neutered male Golden Retriever by rectal enema. Additionally, we performed 16S rRNA sequence analysis, before and after FMT, to evaluate the microbiome diversity.<br><br>RESULTS: Fecal microbiome diversity after FMT resembled that of the healthy donor dog's fecal microbiome, before FMT, which led us to conclude that the fecal microbiome in our patient normalized with FMT. Moreover, the clinical symptoms improved remarkably with regard to the changes in the fecal microbiome. Additionally, we noted no observable side effects during FMT treatment.<br><br>CONCLUSION: This report indicates the efficacy and safety of long-term, periodic FMT for a case of canine IBD based on attenuation of clinical symptoms and changes in fecal microbiome diversity. Therefore, FMT could be chosen as a treatment option for IBD in canines in the future.}, }
@article {pmid31819762, year = {2019}, author = {Jia, Q and Li, H and Zhou, H and Zhang, X and Zhang, A and Xie, Y and Li, Y and Lv, S and Zhang, J}, title = {Role and Effective Therapeutic Target of Gut Microbiota in Heart Failure.}, journal = {Cardiovascular therapeutics}, volume = {2019}, number = {}, pages = {5164298}, pmid = {31819762}, issn = {1755-5922}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bacteria/drug effects/metabolism/*pathogenicity ; Bacterial Translocation ; Diet, Healthy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Heart Failure/metabolism/microbiology/physiopathology/*therapy ; Host-Pathogen Interactions ; Humans ; Intestines/drug effects/*microbiology ; Probiotics/therapeutic use ; Treatment Outcome ; }, abstract = {Although the mechanism of the occurrence and development of heart failure has been continuously explored in the past ten years, the mortality and readmission rate of heart failure is still very high. Modern studies have shown that gut microbiota is associated with a variety of cardiovascular diseases, among which the study of gut microbiota and heart failure attracts particular attention. Therefore, understanding the role of gut microbiota in the occurrence and development of heart failure will help us further understand the pathogenesis of heart failure and provide new ideas for its treatment. This paper introduced intestinal flora and its metabolites, summarized the changes of intestinal flora in patients with heart failure, clarified that intestinal barrier damage and bacterial translocation induced inflammation and immune response aggravated heart failure, and altered intestinal microflora affected various metabolic pathways including trimethylamine/TMAO, SCFA, and Bile acid pathway leads to heart failure. At the same time, regulating intestinal microflora through diet, probiotics, antibiotics, fecal transplantation and microbial enzyme inhibitors has grown up to be a potential treatment for many metabolic disorders.}, }
@article {pmid31819450, year = {2019}, author = {Liang, W and Huang, Y and Tan, X and Wu, J and Duan, J and Zhang, H and Yin, B and Li, Y and Zheng, P and Wei, H and Xie, P}, title = {Alterations Of Glycerophospholipid And Fatty Acyl Metabolism In Multiple Brain Regions Of Schizophrenia Microbiota Recipient Mice.}, journal = {Neuropsychiatric disease and treatment}, volume = {15}, number = {}, pages = {3219-3229}, pmid = {31819450}, issn = {1176-6328}, abstract = {BACKGROUND: Schizophrenia is a debilitating psychiatric disorder characterized by molecular and anatomical abnormalities of multiple brain regions. Our recent study showed that dysbiosis of the gut microbiota contributes to the onset of schizophrenia-relevant behaviors, but the underlying mechanisms remain largely unknown.<br><br>PURPOSE: This study aimed to investigate how gut microbiota shapes metabolic signatures in multiple brain regions of schizophrenia microbiota recipient mice.<br><br>METHODS: Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were used to compare the metabolic signatures in the cortex, cerebellum and striatum of schizophrenia microbiota and healthy microbiota recipient mice. Enrichment analysis was further conducted to uncover the crucial metabolic pathways related to schizophrenia-relevant behaviors.<br><br>RESULTS: We found that the metabolic phenotypes of these three regions were substantially different in schizophrenia microbiota recipient mice from those in healthy microbiota recipient mice. In total, we identified 499 differential metabolites that could discriminate the two groups in the three brain regions. These differential metabolites were mainly involved in glycerophospholipid and fatty acyl metabolism. Moreover, we found four of fatty acyl metabolites that were consistently altered in the three brain regions.<br><br>CONCLUSION: Taken together, our study suggests that alterations of glycerophospholipid and fatty acyl metabolism are implicated in the onset of schizophrenia-relevant behaviors, which may provide a new understanding of the etiology of schizophrenia.}, }
@article {pmid31817895, year = {2019}, author = {Moron, R and Galvez, J and Colmenero, M and Anderson, P and Cabeza, J and Rodriguez-Cabezas, ME}, title = {The Importance of the Microbiome in Critically Ill Patients: Role of Nutrition.}, journal = {Nutrients}, volume = {11}, number = {12}, pages = {}, pmid = {31817895}, issn = {2072-6643}, support = {PI-0206-2016//Junta de Andalucia/ ; }, mesh = {Bacteroidetes/physiology ; Critical Care/*methods ; Critical Illness/*therapy ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Firmicutes/physiology ; *Gastrointestinal Microbiome ; Homeostasis ; Host Microbial Interactions ; Humans ; *Nutritional Support ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; Proteobacteria/pathogenicity ; Synbiotics/administration &amp; dosage ; }, abstract = {Critically ill patients have an alteration in the microbiome in which it becomes a disease-promoting pathobiome. It is characterized by lower bacterial diversity, loss of commensal phyla, like Firmicutes and Bacteroidetes, and a domination of pathogens belonging to the Proteobacteria phylum. Although these alterations are multicausal, many of the treatments administered to these patients, like antibiotics, play a significant role. Critically ill patients also have a hyperpermeable gut barrier and dysregulation of the inflammatory response that favor the development of the pathobiome, translocation of pathogens, and facilitate the emergence of sepsis. In order to restore the homeostasis of the microbiome, several nutritional strategies have been evaluated with the aim to improve the management of critically ill patients. Importantly, enteral nutrition has proven to be more efficient in promoting the homeostasis of the gut microbiome compared to parenteral nutrition. Several nutritional therapies, including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation, are currently being used, showing variable results, possibly due to the unevenness of clinical trial conditions and the fact that the beneficial effects of probiotics are specific to particular species or even strains. Thus, it is of great importance to better understand the mechanisms by which nutrition and supplement therapies can heal the microbiome in critically ill patients in order to finally implement them in clinical practice with optimal safety and efficacy.}, }
@article {pmid31817158, year = {2019}, author = {D'Amico, F and Biagi, E and Rampelli, S and Fiori, J and Zama, D and Soverini, M and Barone, M and Leardini, D and Muratore, E and Prete, A and Gotti, R and Pession, A and Masetti, R and Brigidi, P and Turroni, S and Candela, M}, title = {Enteral Nutrition in Pediatric Patients Undergoing Hematopoietic SCT Promotes the Recovery of Gut Microbiome Homeostasis.}, journal = {Nutrients}, volume = {11}, number = {12}, pages = {}, pmid = {31817158}, issn = {2072-6643}, support = {GR-2013-02357136//Ministero della Salute/ ; }, mesh = {Child ; *Enteral Nutrition ; Fatty Acids, Volatile/analysis/metabolism ; Feces/chemistry ; *Gastrointestinal Microbiome/genetics ; Graft vs Host Disease/prevention &amp; control ; *Hematopoietic Stem Cell Transplantation ; Homeostasis/physiology ; Humans ; *Parenteral Nutrition ; }, abstract = {Hematopoietic stem cell transplantation (HSCT) is the first-line immunotherapy to treat several hematologic disorders, although it can be associated with many complications reducing the survival rate, such as acute graft-versus-host disease (aGvHD) and infections. Given the fundamental role of the gut microbiome (GM) for host health, it is not surprising that a suboptimal path of GM recovery following HSCT may compromise immune homeostasis and/or increase the risk of opportunistic infections, with an ultimate impact in terms of aGvHD onset. Traditionally, the first nutritional approach in post-HSCT patients is parenteral nutrition (PN), which is associated with several clinical adverse effects, supporting enteral nutrition (EN) as a preferential alternative. The aim of the study was to evaluate the impact of EN vs. PN on the trajectory of compositional and functional GM recovery in pediatric patients undergoing HSCT. The GM structure and short-chain fatty acid (SCFA) production profiles were analyzed longitudinally in twenty pediatric patients receiving HSCT-of which, ten were fed post-transplant with EN and ten with total PN. According to our findings, we observed the prompt recovery of a structural and functional eubiotic GM layout post-HSCT only in EN subjects, thus possibly reducing the risk of systemic infections and GvHD onset.}, }
@article {pmid31815741, year = {2020}, author = {Walters, JR and Marchesi, JR}, title = {Chronic diarrhea, bile acids, and Clostridia.}, journal = {The Journal of clinical investigation}, volume = {130}, number = {1}, pages = {77-79}, pmid = {31815741}, issn = {1558-8238}, mesh = {Animals ; Bile ; Bile Acids and Salts ; Clostridiales ; Diarrhea ; Fibroblast Growth Factors ; Humans ; *Irritable Bowel Syndrome ; Mice ; *Microbiota ; }, abstract = {Excessive fecal bile acid (BA) loss causes symptoms in a large proportion of people diagnosed with irritable bowel syndrome with diarrhea, a common functional bowel disorder. This BA diarrhea (BAD) results from increased hepatic synthesis of BAs, with impaired negative feedback regulation by the ileal hormone fibroblast growth factor 19 (FGF19). In this issue of the JCI, Zhao et al. investigated BA metabolism, including fecal BAs, serum BAs, and FGF19, in patients and controls. They identified associations between fecal bacterial BA metabolism and specific microbiota, especially Clostridium scindens. These findings have been tested in a mouse model using microbiota transplants and antibiotic treatment. This group of organisms has potential as a biomarker for BAD and to be a target for therapy.}, }
@article {pmid31813093, year = {2019}, author = {Zhang, X and Tian, H and Chen, Q and Qin, H and Li, N}, title = {Fecal microbiota transplantation: standardization or diversification?.}, journal = {Science China. Life sciences}, volume = {62}, number = {12}, pages = {1714-1716}, doi = {10.1007/s11427-019-1592-8}, pmid = {31813093}, issn = {1869-1889}, mesh = {Biological Therapy/*standards ; Clostridioides difficile/metabolism ; Fecal Microbiota Transplantation/*standards ; Feces/*microbiology ; Humans ; Microbiota/*physiology ; Risk Assessment ; Tissue Donors ; Treatment Outcome ; }, }
@article {pmid31811801, year = {2020}, author = {Janket, SJ and Ackerson, LK and Diamandis, EP}, title = {Potential risks in fecal microbiota transplantation.}, journal = {Clinical chemistry and laboratory medicine}, volume = {58}, number = {4}, pages = {e95}, doi = {10.1515/cclm-2019-1076}, pmid = {31811801}, issn = {1437-4331}, mesh = {Autoimmune Diseases/etiology ; Bacteremia/etiology ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Immunocompromised Host ; Risk ; Sepsis/etiology ; }, }
@article {pmid31811292, year = {2020}, author = {Sun, Y and Baptista, LC and Roberts, LM and Jumbo-Lucioni, P and McMahon, LL and Buford, TW and Carter, CS}, title = {The Gut Microbiome as a Therapeutic Target for Cognitive Impairment.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {75}, number = {7}, pages = {1242-1250}, pmid = {31811292}, issn = {1758-535X}, support = {K02 AG062498/AG/NIA NIH HHS/United States ; K12 GM088010/GM/NIGMS NIH HHS/United States ; R01 AG054538/AG/NIA NIH HHS/United States ; }, mesh = {Cognitive Dysfunction/*etiology/pathology/*prevention &amp; control ; Diet ; Dietary Fiber/administration &amp; dosage ; Exercise ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Probiotics/therapeutic use ; }, abstract = {Declining cognitive functions in older individuals have enormous emotional, clinical, and public health consequences. Thus, therapeutics for preserving function and keeping older adults living independently are imperative. Aging is associated dysbiosis, defined as a loss of number and diversity in gut microbiota, which has been linked with various aspects of cognitive functions. Therefore, the gut microbiome has the potential to be an important therapeutic target for symptoms of cognitive impairment. In this review, we summarize the current literature regarding the potential for gut-targeted therapeutic strategies for prevention/treatment of the symptoms of cognitive impairment. Specifically, we discuss four primary therapeutic strategies: wild-type and genetically modified probiotics, fecal microbiota transplantation, physical exercise, and high-fiber diets and specifically link these therapies to reducing inflammation. These strategies may hold promise as treatment paradigm symptoms related to cognitive impairment.}, }
@article {pmid31808861, year = {2019}, author = {Severyn, CJ and Brewster, R and Andermann, TM}, title = {Microbiota modification in hematology: still at the bench or ready for the bedside?.}, journal = {Hematology. American Society of Hematology. Education Program}, volume = {2019}, number = {1}, pages = {303-314}, pmid = {31808861}, issn = {1520-4383}, support = {KL2 TR001083/TR/NCATS NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; T32 DK098132/DK/NIDDK NIH HHS/United States ; KL2 TR003143/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {Fecal Microbiota Transplantation ; Female ; *Hematology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; *Microbiota ; Middle Aged ; Probiotics/therapeutic use ; *Translational Research, Biomedical ; Treatment Outcome ; }, abstract = {Growing evidence suggests that human microbiota likely influence diverse processes including hematopoiesis, chemotherapy metabolism, and efficacy, as well as overall survival in patients with hematologic malignancies and other cancers. Both host genetic susceptibility and host-microbiota interactions may impact cancer risk and response to treatment; however, microbiota have the potential to be uniquely modifiable and accessible targets for treatment. Here, we focus on strategies to modify microbiota composition and function in patients with cancer. First, we evaluate the use of fecal microbiota transplant to restore microbial equilibrium following perturbation by antibiotics and chemotherapy, and as a treatment of complications of hematopoietic stem cell transplantation (HSCT), such as graft-versus-host disease and colonization with multidrug-resistant organisms. We then address the potential use of both probiotics and dietary prebiotic compounds in targeted modulation of the microbiota intended to improve outcomes in hematologic diseases. With each type of therapy, we highlight the role that abnormal, or dysbiotic, microbiota play in disease, treatment efficacy, and toxicity and evaluate their potential promise as emerging strategies for microbiota manipulation in patients with hematologic malignancies and in those undergoing HSCT.}, }
@article {pmid31808596, year = {2020}, author = {Mohammed, Y and Kootte, RS and Kopatz, WF and Borchers, CH and Büller, HR and Versteeg, HH and Nieuwdorp, M and van Mens, TE}, title = {The intestinal microbiome potentially affects thrombin generation in human subjects.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {18}, number = {3}, pages = {642-650}, pmid = {31808596}, issn = {1538-7836}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Research Subjects ; Thrombin ; }, abstract = {BACKGROUND: The intestinal microbiome plays a versatile role in the etiology of arterial thrombosis. In venous thrombosis, driven chiefly by plasma coagulation, no such role has yet been established. We hypothesized that the intestinal microbiome composition affects coagulation in humans.<br><br>METHODS: We used healthy donor fecal microbiota transplant (FMT) to experimentally change the microbiome composition in metabolic syndrome patients. Thirty-five subjects were randomized in a blinded fashion to healthy donor FMT or autologous FMT as a control in a 2:1 ratio. We measured thrombin generation at baseline and after 6&#xa0;weeks using automated calibrated thrombinography, and we determined plasma abundance of 32 coagulation related proteins using a targeted mass spectrometry-based quantitative proteomics assay with heavy labeled internal standards.<br><br>RESULTS: Healthy donor FMT prolonged the thrombinography lag time (median delta 0.0 versus 0.25&#xa0;minutes, P&#xa0;=&#xa0;.039). The other thrombinography parameters showed no significant difference. Unsupervised cluster analysis suggested overall downregulation of coagulation related plasma proteins in subject clusters containing predominantly subjects that had a metabolic response to healthy donor FMT. FMT treatment status itself showed no clear clustering pattern with up- or downregulation, however, and proteins did not cluster according to an apparent biological grouping.<br><br>DISCUSSION: A single healthy donor FMT tends to modestly suppress the onset thrombin generation in metabolic syndrome patients, representing initial proof-of-principle that the intestinal microbiota composition might affect the coagulation system in humans. The findings merit external validation as a role for intestinal microbiota in coagulation can have clinically important implications.}, }
@article {pmid31806059, year = {2020}, author = {Vaughn, VM and Greene, MT and Ratz, D and Fowler, KE and Krein, SL and Flanders, SA and Dubberke, ER and Saint, S and Patel, PK}, title = {Antibiotic stewardship teams and Clostridioides difficile practices in United States hospitals: A national survey in The Joint Commission antibiotic stewardship standard era.}, journal = {Infection control and hospital epidemiology}, volume = {41}, number = {2}, pages = {143-148}, doi = {10.1017/ice.2019.313}, pmid = {31806059}, issn = {1559-6834}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Antimicrobial Stewardship/*organization &amp; administration/*standards ; Clostridium Infections/*prevention &amp; control ; Cross Infection/prevention &amp; control ; Hospitals ; Humans ; Infection Control/methods ; Practice Guidelines as Topic ; Surveys and Questionnaires ; United States ; }, abstract = {OBJECTIVE: Clostridioides difficile infection (CDI) can be prevented through infection prevention practices and antibiotic stewardship. Diagnostic stewardship (ie, strategies to improve use of microbiological testing) can also improve antibiotic use. However, little is known about the use of such practices in US hospitals, especially after multidisciplinary stewardship programs became a requirement for US hospital accreditation in 2017. Thus, we surveyed US hospitals to assess antibiotic stewardship program composition, practices related to CDI, and diagnostic stewardship.<br><br>METHODS: Surveys were mailed to infection preventionists at 900 randomly sampled US hospitals between May and October 2017. Hospitals were surveyed on antibiotic stewardship programs; CDI prevention, treatment, and testing practices; and diagnostic stewardship strategies. Responses were compared by hospital bed size using weighted logistic regression.<br><br>RESULTS: Overall, 528 surveys were completed (59% response rate). Almost all (95%) responding hospitals had an antibiotic stewardship program. Smaller hospitals were less likely to have stewardship team members with infectious diseases (ID) training, and only 41% of hospitals met The Joint Commission accreditation standards for multidisciplinary teams. Guideline-recommended CDI prevention practices were common. Smaller hospitals were less likely to use high-tech disinfection devices, fecal microbiota transplantation, or diagnostic stewardship strategies.<br><br>CONCLUSIONS: Following changes in accreditation standards, nearly all US hospitals now have an antibiotic stewardship program. However, many hospitals, especially smaller hospitals, appear to struggle with access to ID expertise and with deploying diagnostic stewardship strategies. CDI prevention could be enhanced through diagnostic stewardship and by emphasizing the role of non-ID-trained pharmacists and clinicians in antibiotic stewardship.}, }
@article {pmid31805871, year = {2019}, author = {Jahn, B and Sroczynski, G and Bundo, M and Mühlberger, N and Puntscher, S and Todorovic, J and Rochau, U and Oberaigner, W and Koffijberg, H and Fischer, T and Schiller-Fruehwirth, I and Öfner, D and Renner, F and Jonas, M and Hackl, M and Ferlitsch, M and Siebert, U and , }, title = {Effectiveness, benefit harm and cost effectiveness of colorectal cancer screening in Austria.}, journal = {BMC gastroenterology}, volume = {19}, number = {1}, pages = {209}, pmid = {31805871}, issn = {1471-230X}, mesh = {Adult ; Aged ; Austria ; Colonic Neoplasms/*diagnosis/prevention &amp; control/psychology ; Colonoscopy/adverse effects ; Cost-Benefit Analysis ; Guaiac ; Humans ; Indicators and Reagents ; Markov Chains ; Mass Screening/economics ; Middle Aged ; Occult Blood ; Quality-Adjusted Life Years ; Rectal Neoplasms/*diagnosis/prevention &amp; control/psychology ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Clear evidence on the benefit-harm balance and cost effectiveness of population-based screening for colorectal cancer (CRC) is missing. We aim to systematically evaluate the long-term effectiveness, harms and cost effectiveness of different organized CRC screening strategies in Austria.<br><br>METHODS: A decision-analytic cohort simulation model for colorectal adenoma and cancer with a lifelong time horizon was developed, calibrated to the Austrian epidemiological setting and validated against observed data. We compared four strategies: 1) No Screening, 2) FIT: annual immunochemical fecal occult blood test age 40-75&#x2009;years, 3) gFOBT: annual guaiac-based fecal occult blood test age 40-75&#x2009;years, and 4) COL: 10-yearly colonoscopy age 50-70&#x2009;years. Predicted outcomes included: benefits expressed as life-years gained [LYG], CRC-related deaths avoided and CRC cases avoided; harms as additional complications due to colonoscopy (physical harm) and positive test results (psychological harm); and lifetime costs. Tradeoffs were expressed as incremental harm-benefit ratios (IHBR, incremental positive test results per LYG) and incremental cost-effectiveness ratios [ICER]. The perspective of the Austrian public health care system was adopted. Comprehensive sensitivity analyses were performed to assess uncertainty.<br><br>RESULTS: The most effective strategies were FIT and COL. gFOBT was less effective and more costly than FIT. Moving from COL to FIT results in an incremental unintended psychological harm of 16 additional positive test results to gain one life-year. COL was cost saving compared to No Screening. Moving from COL to FIT has an ICER of 15,000 EUR per LYG.<br><br>CONCLUSIONS: Organized CRC-screening with annual FIT or 10-yearly colonoscopy is most effective. The choice between these two options depends on the individual preferences and benefit-harm tradeoffs of screening candidates.}, }
@article {pmid31803633, year = {2019}, author = {He, Y and Li, X and Yu, H and Ge, Y and Liu, Y and Qin, X and Jiang, M and Wang, X}, title = {The Functional Role of Fecal Microbiota Transplantation on Dextran Sulfate Sodium-Induced Colitis in Mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {393}, pmid = {31803633}, issn = {2235-2988}, mesh = {Animals ; Biomarkers ; Biopsy ; Colitis/diagnosis/*etiology/*therapy ; Cytokines/metabolism ; Dextran Sulfate/*adverse effects ; Disease Models, Animal ; *Fecal Microbiota Transplantation/methods ; Feces/chemistry/microbiology ; Gastrointestinal Microbiome ; Intestinal Mucosa ; Male ; Mice ; Treatment Outcome ; }, abstract = {Increasingly studies revealed that dysbiosis of gut microbiota plays a pivotal role in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) has drawn more and more attention and become an important therapeutic approach. This study aims to examine the facts about the effective components and look into potential mechanisms of FMT. Colitis was induced by 3% (w/v) dextran sulfate sodium (DSS) in drinking water for 7 days. Colitis mice were administered by oral gavage with fecal suspension, fecal supernatant, fecal bacteria, or boiling-killed fecal bacteria from healthy controls and the disease activity index was monitored daily. On the seventh day, mice were euthanized. The length, histological score, parameters related to inflammation, gut barrier functions of the colon, activities of digestive protease and β-glucuronidase in feces were measured. All of the four fecal components showed certain degree of efficacy in DSS-induced colitis, while transplantation of fecal suspension showed the most potent effect as demonstrated by less body weight loss, lower disease activity scores, more expression of tight junction proteins and TRAF6 and IκBα, less expression of TNF-α, IL-1β, IL-10, TLR-4, and MyD88 in gut tissue, as well as restoration of fecal β-glucuronidase and decreases in fecal digestive proteases. These results provide a novel insight into the possible mechanism of FMT and may help to improve and optimize clinical use of FMT.}, }
@article {pmid31803631, year = {2019}, author = {Yin, A and Luo, Y and Chen, W and He, M and Deng, JH and Zhao, N and Cao, L and Wang, L}, title = {FAM96A Protects Mice From Dextran Sulfate Sodium (DSS)-Induced Colitis by Preventing Microbial Dysbiosis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {381}, pmid = {31803631}, issn = {2235-2988}, mesh = {Animals ; Biomarkers ; Carrier Proteins/*genetics ; Cell Membrane Permeability ; Colitis/*drug therapy/*etiology/pathology ; Dextran Sulfate/*adverse effects ; Disease Models, Animal ; Dysbiosis/*drug therapy ; Gastrointestinal Microbiome/*drug effects ; Immunohistochemistry ; Inflammatory Bowel Diseases/etiology/metabolism/pathology ; Intestinal Mucosa/immunology/metabolism/microbiology/pathology ; Mice ; Mice, Knockout ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Family with sequence similarity 96 member A (FAM96A) is an evolutionarily conserved intracellular protein that is involved in the maturation of the Fe/S protein, iron regulatory protein 1 (IRP1), and the mitochondria-related apoptosis of gastrointestinal stromal tumor cells. In this study, we used a mouse model of chemically induced colitis to investigate the physiological role of FAM96A in intestinal homeostasis and inflammation. At baseline, colons from Fam96a[-/-] mice exhibited microbial dysbiosis, dysregulated epithelial cell turnover, an increased number of goblet cells, and disordered tight junctions with functional deficits affecting intestinal permeability. After cohousing, the differences between wild-type and Fam96a[-/-] colons were abrogated, suggesting that FAM96A affects colonic epithelial cells in a microbiota-dependent manner. Fam96a deficiency in mice resulted in increased susceptibility to dextran sulfate sodium (DSS)-induced colitis. Importantly, the colitogenic activity of Fam96a[-/-] intestinal microbiota was transferable to wild-type littermate mice via fecal microbial transplantation (FMT), leading to exacerbation of DSS-induced colitis. Taken together, our data indicate that FAM96A helps to maintain colonic homeostasis and protect against DSS-induced colitis by preventing gut microbial dysbiosis. This study used gene knockout animals to help to understand the in vivo effects of the Fam96a gene for the first time and provides new evidence regarding host-microbiota interactions.}, }
@article {pmid31803254, year = {2019}, author = {Yalchin, M and Segal, JP and Mullish, BH and Quraishi, MN and Iqbal, TH and Marchesi, JR and Hart, AL}, title = {Gaps in knowledge and future directions for the use of faecal microbiota transplant in the treatment of inflammatory bowel disease.}, journal = {Therapeutic advances in gastroenterology}, volume = {12}, number = {}, pages = {1756284819891038}, pmid = {31803254}, issn = {1756-283X}, support = {EME/13/179/01/DH_/Department of Health/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Faecal microbiota transplant (FMT) has now been established into clinical guidelines for the treatment of recurrent and refractory Clostridioides difficile infection (CDI). Its therapeutic application in inflammatory bowel disease (IBD) is currently at an early stage. To date, there have been four randomized controlled trials for FMT in IBD and a multitude of observational studies. However, significant gaps in our knowledge regarding optimum methods for FMT preparation, technical aspects and logistics of its administration, as well as mechanistic underpinnings, still remain. In this article, we aim to highlight these gaps by reviewing evidence and making key recommendations on the direction of future studies in this field. In addition, we provide an overview of the current evidence of potential mechanisms of FMT in treating IBD.}, }
@article {pmid31801387, year = {2020}, author = {Oksi, J and Anttila, VJ and Mattila, E}, title = {Treatment of Clostridioides (Clostridium) difficile infection.}, journal = {Annals of medicine}, volume = {52}, number = {1-2}, pages = {12-20}, pmid = {31801387}, issn = {1365-2060}, mesh = {Age Factors ; Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Broadly Neutralizing Antibodies/therapeutic use ; Clostridium Infections/mortality/*therapy ; Fecal Microbiota Transplantation ; Fidaxomicin/therapeutic use ; Humans ; Practice Guidelines as Topic ; Recurrence ; Risk Factors ; Severity of Illness Index ; Vancomycin/therapeutic use ; }, abstract = {Clostridioides (formerly: Clostridium) difficile infection (CDI) is a major cause of diarrhoea for inpatients as well as outpatients. Usually, CDI is healthcare-associated but the number of community-acquired infections is increasing. CDI is generally associated with changes in the normal intestinal microbiota caused by administration of antibiotics. Elderly and immunocompromised patients are at greater risk for CDI and CDI recurrence. Recently, the treatment options of CDI have undergone major changes: current recommendations speak against using metronidazole for primary CDI, fidaxomicin and bezlotoxumab have been added to the treatment armamentarium and microbial replacement therapies have emerged. Several other therapies are undergoing clinical trials. In this article, we review current treatment guidelines, present the most recent data on the options to treat CDI and glance towards future developments.KEY MESSAGESThe cornerstones for the treatment of CDI are vancomycin and fidaxomicin. Metronidazole should be used only in mild-to-moderate disease in younger patients who have no or only few risk factors for recurrence.In recurrent CDI, bezlotoxumab infusion (a monoclonal antibody against C. difficile toxin B) may be considered as an adjunctive therapeutic strategy in addition to the standard care provided to patients with several risk factors for recurrence.Faecal microbiota transplantation (FMT) should be offered to patients with frequently recurring CDI.}, }
@article {pmid31798584, year = {2019}, author = {Pearson, JA and Tai, N and Ekanayake-Alper, DK and Peng, J and Hu, Y and Hager, K and Compton, S and Wong, FS and Smith, PC and Wen, L}, title = {Norovirus Changes Susceptibility to Type 1 Diabetes by Altering Intestinal Microbiota and Immune Cell Functions.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2654}, pmid = {31798584}, issn = {1664-3224}, support = {MR/K021141/1/MRC_/Medical Research Council/United Kingdom ; P30 DK045735/DK/NIDDK NIH HHS/United States ; R01 DK092882/DK/NIDDK NIH HHS/United States ; R01 DK100500/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Caliciviridae Infections/*immunology ; Diabetes Mellitus, Type 1/*immunology ; Disease Susceptibility/immunology/*virology ; Gastrointestinal Microbiome/*immunology ; Mice ; Mice, Inbred NOD ; Norovirus/immunology ; T-Lymphocytes/*immunology ; }, abstract = {Environmental factors contribute to Type 1 diabetes (T1D) susceptibility. The gut microbiome, which includes bacteria, viruses, and fungi, contributes to this environmental influence, and can induce immunological changes. The gut viral component of the microbiome, related to T1D has mostly focused on coxsackieviruses and rotavirus. The role of norovirus, another common enteric virus, in susceptibility to T1D was hitherto unknown. Norovirus is highly infectious and encountered by many children. We studied the mouse norovirus 4 (MNV4), related to human noroviruses, in the Non-obese diabetic (NOD) mouse model, to determine its role in influencing susceptibility to T1D. We infected MNV-free NOD mice with MNV4 by exposing the mice to MNV4-positive bedding from an endemically-infected mouse colony to mimic a natural infection. Control MNV-free NOD mice were exposed to MNV-free bedding from the same colony. Interestingly, MNV4 infection protected NOD mice from the development of T1D and was associated with an expansion of Tregs and reduced proinflammatory T cells. We also found MNV4 significantly modified the gut commensal bacteria composition, promoting increased α-diversity and Firmicutes/Bacteroidetes ratio. To elucidate whether T1D protection was directly related to MNV4, or indirectly through modulating gut microbiota, we colonized germ-free (GF) NOD mice with the MNV4-containing or non-MNV4-containing viral filtrate, isolated from filtered fecal material. We found that MNV4 induced significant changes in mucosal immunity, including altered Tuft cell markers, cytokine secretion, antiviral immune signaling markers, and the concentration of mucosal antibodies. Systemically, MNV4-infection altered the immune cells including B cell subsets, macrophages and T cells, and especially induced an increase in Treg number and function. Furthermore, in vitro primary exposure of the norovirus filtrate to naïve splenocytes identified significant increases in the proportion of activated and CTLA4-expressing Tregs. Our data provide novel knowledge that norovirus can protect NOD mice from T1D development by inducing the expansion of Tregs and reducing inflammatory T cells. Our study also highlights the importance of distinguishing the mucosal immunity mediated by bacteria from that by enteric viruses.}, }
@article {pmid31798539, year = {2019}, author = {Wang, Z and Hua, W and Li, C and Chang, H and Liu, R and Ni, Y and Sun, H and Li, Y and Wang, X and Hou, M and Liu, Y and Xu, Z and Ji, M}, title = {Protective Role of Fecal Microbiota Transplantation on Colitis and Colitis-Associated Colon Cancer in Mice Is Associated With Treg Cells.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2498}, pmid = {31798539}, issn = {1664-302X}, abstract = {Colitis-associated cancer (CAC) is the most serious outcome of inflammatory bowel disease, which has an alteration of commensal intestinal microbiota. However, the role of intestinal microbiota on CAC progression is not well-understood. Fecal microbiota transplantation (FMT) was used for treating murine azoxymethane-dextran sodium sulfate (AOM-DSS) model of CAC. Composition of gut microbiota during FMT treatment was analyzed. RT-PCR and ELISA were used to detect the inflammatory factors, and immunofluorescence was applied to examine the phospho-nuclear factor (NF)-κB p65/p100 and Ki67-positive cells in the colons. In addition, flow cytometry was performed to analyze the immune cell after FMT treatment. Rehabilitation of the intestinal microbiota by FMT restored both the ratio and diversity of microbiota during CAC progression. Remarkably, a favorable morphometric outcome characterized by decreased tumor load and size was observed in CAC mice with FMT treatment. In addition, an anti-inflammatory function of FMT was demonstrated by decreasing pro-inflammatory factors but increasing anti-inflammatory factors through inhibiting canonical NF-κB activity and cellular proliferation in colons of CAC mice. The expression of CD4[+]CD25[+]Foxp3[+] regulatory T cells (Tregs) was significantly increased after FMT treatment in CAC mice, but not T helper (Th)1/2/17 cells. Our study aids in the understanding of CAC pathogenesis and reveals a previously unrecognized role for FMT in the treatment of CAC through restoring the intestinal microbiota and inducing regulatory T cells.}, }
@article {pmid31797927, year = {2019}, author = {Magruder, M and Sholi, AN and Gong, C and Zhang, L and Edusei, E and Huang, J and Albakry, S and Satlin, MJ and Westblade, LF and Crawford, C and Dadhania, DM and Lubetzky, M and Taur, Y and Littman, E and Ling, L and Burnham, P and De Vlaminck, I and Pamer, E and Suthanthiran, M and Lee, JR}, title = {Gut uropathogen abundance is a risk factor for development of bacteriuria and urinary tract infection.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {5521}, pmid = {31797927}, issn = {2041-1723}, support = {DP2 AI138242/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R21 AI133331/AI/NIAID NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; K23 AI124464/AI/NIAID NIH HHS/United States ; R37 AI051652/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/classification/*genetics ; Bacterial Infections/*microbiology ; Bacteriuria/etiology/microbiology/urine ; DNA, Bacterial/analysis/*genetics ; Escherichia coli Infections/etiology/microbiology ; Feces/microbiology ; Gastrointestinal Microbiome/genetics ; Humans ; Kidney Transplantation/adverse effects/methods ; RNA, Ribosomal, 16S/*genetics ; Risk Factors ; Urinary Tract Infections/etiology/*microbiology/urine ; }, abstract = {The origin of most bacterial infections in the urinary tract is often presumed to be the gut. Herein, we investigate the relationship between the gut microbiota and future development of bacteriuria and urinary tract infection (UTI). We perform gut microbial profiling using 16S rRNA gene deep sequencing on 510 fecal specimens from 168 kidney transplant recipients and metagenomic sequencing on a subset of fecal specimens and urine supernatant specimens. We report that a 1% relative gut abundance of Escherichia is an independent risk factor for Escherichia bacteriuria and UTI and a 1% relative gut abundance of Enterococcus is an independent risk factor for Enterococcus bacteriuria. Strain analysis establishes a close strain level alignment between species found in the gut and in the urine in the same subjects. Our results support a gut microbiota-UTI axis, suggesting that modulating the gut microbiota may be a potential novel strategy to prevent UTIs.}, }
@article {pmid31797303, year = {2020}, author = {Patel, VC and Williams, R}, title = {Antimicrobial resistance in chronic liver disease.}, journal = {Hepatology international}, volume = {14}, number = {1}, pages = {24-34}, pmid = {31797303}, issn = {1936-0541}, mesh = {*Anti-Bacterial Agents ; *Antimicrobial Stewardship ; *Drug Resistance, Bacterial ; *Hepatitis, Chronic ; Humans ; }, abstract = {High levels of antimicrobial drug resistance deleteriously affecting the outcome of treatment with antibacterial agents are causing increasing concern worldwide. This is particularly worrying in patients with cirrhosis with a depressed immune system and heightened susceptibility to infection. Antibiotics have to be started early before results of microbiological culture are available. Current guidelines for the empirical choice of antibiotics in this situation are not very helpful, and embracing antimicrobial stewardship including rapid de-escalation of therapy are not sufficiently emphasised. Multi-drug resistant organism rates to quinolone drugs of up to 40% are recorded in patients with spontaneous bacterial peritonitis on prophylactic antibiotics, leading to a break-through recurrence of intra-peritoneal infection. Also considered in this review is the value of rifaximin-α, non-selective beta-blockers, and concerns around proton pump inhibitor drug use. Fecal microbial transplantation and other gut-targeting therapies in lessening gut bacterial translocation are a promising approach, and new molecular techniques for determining bacterial sensitivity will allow more specific targeted therapy.}, }
@article {pmid31797125, year = {2020}, author = {Kochi, M and Egi, H and Adachi, T and Takakura, Y and Mukai, S and Taguchi, K and Nakashima, I and Sumi, Y and Akabane, S and Sato, K and Yoshinaka, H and Hattori, M and Ohdan, H}, title = {Preoperative incremental maximum squeeze pressure as a predictor of fecal incontinence after very low anterior resection for low rectal cancer.}, journal = {Surgery today}, volume = {50}, number = {5}, pages = {516-524}, pmid = {31797125}, issn = {1436-2813}, mesh = {Anal Canal/*physiopathology ; Digestive System Surgical Procedures/methods ; *Fecal Incontinence/epidemiology ; Manometry ; *Postoperative Complications/epidemiology ; Predictive Value of Tests ; Preoperative Period ; *Pressure ; Rectal Neoplasms/*physiopathology/*surgery ; Rectum/*physiopathology ; Risk Factors ; }, abstract = {PURPOSE: Very low anterior resection (VLAR) is performed widely, but some patients are left with fecal incontinence (FI), which compromises their quality of life (QOL) severely. This study sought to identify the predictive factors of postoperative FI after VLAR, which remain unclear.<br><br>METHODS: We evaluated the anorectal manometry data of patients who underwent VLAR to identify the risk factors for postoperative FI among the various clinicopathological factors and manometric characteristics. FI and QOL were analyzed using the Wexner score and EORTC QLQ-C30, respectively.<br><br>RESULTS: The subjects of this study were 40 patients who underwent VLAR for low rectal cancer between April, 2015 and May, 2018. There were 11 (27%) patients in the major-FI group and 29 (73%) in the minor-FI group. Multivariate analysis revealed that low preoperative incremental maximum squeeze pressure (iMSP) was an independent risk factor for postoperative major-FI. Postoperative QOL tended to be worse in the major-FI group.<br><br>CONCLUSIONS: Preoperative low iMSP increases the risk of major-FI and impaired QOL after VLAR. This highlights the importance of performing preoperative anorectal manometry to evaluate the patient's anal function as well as to select the most appropriate operative procedure and early multifaceted treatment such as medication, rehabilitation, and biofeedback for postoperative FI.}, }
@article {pmid31792054, year = {2020}, author = {Rahfeld, P and Withers, SG}, title = {Toward universal donor blood: Enzymatic conversion of A and B to O type.}, journal = {The Journal of biological chemistry}, volume = {295}, number = {2}, pages = {325-334}, pmid = {31792054}, issn = {1083-351X}, support = {//CIHR/Canada ; }, mesh = {ABO Blood-Group System/*metabolism ; Animals ; Bacteria/enzymology ; Biocatalysis ; *Biotechnology/methods ; *Blood Donors ; Blood Transfusion ; Glycoside Hydrolases/*metabolism ; Hexosaminidases/metabolism ; Humans ; Models, Molecular ; alpha-Galactosidase/metabolism ; }, abstract = {Transfusion of blood, or more commonly red blood cells (RBCs), is integral to health care systems worldwide but requires careful matching of blood types to avoid serious adverse consequences. Of the four main blood types, A, B, AB, and O, only O can be given to any patient. This universal donor O-type blood is crucial for emergency situations where time or resources for typing are limited, so it is often in short supply. A and B blood differ from the O type in the presence of an additional sugar antigen (GalNAc and Gal, respectively) on the core H-antigen found on O-type RBCs. Thus, conversion of A, B, and AB RBCs to O-type RBCs should be achievable by removal of that sugar with an appropriate glycosidase. The first demonstration of a B-to-O conversion by Goldstein in 1982 required massive amounts of enzyme but enabled proof-of-principle transfusions without adverse effects in humans. New α-galactosidases and α-N-acetylgalactosaminidases were identified by screening bacterial libraries in 2007, allowing improved conversion of B and the first useful conversions of A-type RBCs, although under constrained conditions. In 2019, screening of a metagenomic library derived from the feces of an AB donor enabled discovery of a significantly more efficient two-enzyme system, involving a GalNAc deacetylase and a galactosaminidase, for A conversion. This promising system works well both in standard conditions and in whole blood. We discuss remaining challenges and opportunities for the use of such enzymes in blood conversion and organ transplantation.}, }
@article {pmid31791407, year = {2019}, author = {Sarveazad, A and Babahajian, A and Yari, A and Rayner, CK and Mokhtare, M and Babaei-Ghazani, A and Agah, S and Mahjoubi, B and Shamseddin, J and Yousefifard, M}, title = {Combination of laser and human adipose-derived stem cells in repair of rabbit anal sphincter injury: a new therapeutic approach.}, journal = {Stem cell research &amp; therapy}, volume = {10}, number = {1}, pages = {367}, pmid = {31791407}, issn = {1757-6512}, mesh = {Actins/genetics/metabolism ; Adipocytes/cytology ; Anal Canal/injuries/pathology ; Animals ; Collagen/genetics/metabolism ; Colonic Diseases/pathology/*therapy ; Electromyography ; Gene Expression Regulation ; Humans ; Ki-67 Antigen/genetics/metabolism ; Lasers, Semiconductor/therapeutic use ; *Low-Level Light Therapy ; Male ; Rabbits ; Sphincterotomy ; *Stem Cell Transplantation ; Stem Cells/cytology/metabolism ; }, abstract = {BACKGROUND: Anal sphincter injury leads to fecal incontinence. Based on the regenerative capability of laser and human adipose-derived stem cells (hADSCs), this study was designed to assess the effects of co-application of these therapies on anal sphincter recovery after injury.<br><br>DESIGN: Male rabbits were assigned to equal groups (n&#x2009;=&#x2009;7) including control, sphincterotomy, sphincterotomy treated with laser (660&#x2009;nm, 90&#xa0;s, immediately after sphincterotomy, daily, 14&#x2009;days), hADSCs (2&#x2009;&#xd7;&#x2009;10[6] hADSCs injected into injured area of the sphincter immediately after sphincterotomy), and laser&#x2009;+&#x2009;hADSCs. Ninety&#x2009;days after sphincterotomy, manometry and electromyography were performed, sphincter collagen content was evaluated, and Ki67, myosin heavy chain (MHC), skeletal muscle alpha-actin (ACTA1), vascular endothelial growth factor A (VEGFA), and vimentin mRNA gene expression were assessed.<br><br>RESULTS: The laser&#x2009;+&#x2009;hADSCs group had a higher resting pressure compared with the sphincterotomy (p&#x2009;<&#x2009;0.0001), laser (p&#x2009;<&#x2009;0.0001), and hADSCs (p&#x2009;=&#x2009;0.04) groups. Maximum squeeze pressure was improved in all treated animals compared with the sphincterotomized animals (p&#x2009;<&#x2009;0.0001), without a significant difference between treatments (p&#x2009;>&#x2009;0.05). In the laser&#x2009;+&#x2009;hADSCs group, motor unit numbers were higher than those in the laser group (p&#x2009;<&#x2009;0.0001) but did not differ from the hADSCs group (p&#x2009;=&#x2009;0.075). Sphincterotomy increased collagen content, but the muscle content (p&#x2009;=&#x2009;0.36) and collagen content (p&#x2009;=&#x2009;0.37) were not significantly different between the laser&#x2009;+&#x2009;hADSCs and control groups. Laser&#x2009;+&#x2009;hADSCs increased ACTA1 (p&#x2009;=&#x2009;0.001) and MHC (p&#x2009;<&#x2009;0.0001) gene expression compared with laser or hADSCs alone and was associated with increased VEGFA (p&#x2009;=&#x2009;0.009) and Ki67 mRNA expression (p&#x2009;=&#x2009;0.01) and decreased vimentin mRNA expression (p&#x2009;<&#x2009;0.0001) compared with laser.<br><br>CONCLUSION: The combination of laser and hADSCs appears more effective than either treatment alone for promoting myogenesis, angiogenesis, and functional recovery after anal sphincterotomy.}, }
@article {pmid31789724, year = {2020}, author = {Canakis, A and Haroon, M and Weber, HC}, title = {Irritable bowel syndrome and gut microbiota.}, journal = {Current opinion in endocrinology, diabetes, and obesity}, volume = {27}, number = {1}, pages = {28-35}, pmid = {31789724}, issn = {1752-2978}, mesh = {Diet, Carbohydrate-Restricted ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Irritable Bowel Syndrome/etiology/*microbiology/*therapy ; Quality of Life ; Rifaximin/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: To provide an overview of recent studies exploring the gut microbiota in pathogenesis and treatment of irritable bowel syndrome (IBS).<br><br>RECENT FINDINGS: Primary bacterial gut disturbances have been linked to the development and severity of IBS. Dysbiosis, or alteration in the normal intestinal flora, modulates intestinal permeability, inflammation, gut motility and likely quality of life. These biomechanical changes are associated with enteric and central nervous system processing as well. When compared to healthy controls, IBS patients display poor quality of life measures and are at increased risk of depression and anxiety. The severity of psychological and gastrointestinal symptoms in IBS has been linked with a distinct intestinal microbiota signature. Efforts to modulate intestinal dysbiosis in IBS have shown little improvement in large systematic reviews. The low FODMAP diet reduces bacteria, such as Bifidobacterum and Actinobacteria. Although rifaximin improves symptoms, it may only stimulate a transient effect on the gut microbiota. Fecal microbiota transplant does not provide prolonged symptom relief in IBS.<br><br>SUMMARY: This review elucidates recent advances in IBS and the gut microbiota. Microbiota changes are one underlying factor in perpetuating global IBS symptoms. The opportunity to exploit this disturbance through treatment modalities requires further investigation.}, }
@article {pmid31787855, year = {2019}, author = {Grinspan, A}, title = {Fecal Microbiota Transplantation in Inflammatory Bowel Disease Patients With Clostridium difficile Infection.}, journal = {Gastroenterology &amp; hepatology}, volume = {15}, number = {9}, pages = {481-483}, pmid = {31787855}, issn = {1554-7914}, }
@article {pmid31786155, year = {2020}, author = {Liu, Y and Wang, Y and Ni, Y and Cheung, CKY and Lam, KSL and Wang, Y and Xia, Z and Ye, D and Guo, J and Tse, MA and Panagiotou, G and Xu, A}, title = {Gut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention.}, journal = {Cell metabolism}, volume = {31}, number = {1}, pages = {77-91.e5}, doi = {10.1016/j.cmet.2019.11.001}, pmid = {31786155}, issn = {1932-7420}, mesh = {Adult ; Algorithms ; Animals ; Bacteria/classification ; Diet ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Glucose/metabolism ; *High-Intensity Interval Training ; Humans ; Insulin Resistance ; Machine Learning ; Male ; Metabolome ; Mice ; Mice, Inbred C57BL ; Middle Aged ; *Prediabetic State/microbiology/prevention &amp; control ; }, abstract = {Exercise is an effective strategy for diabetes management but is limited by the phenomenon of exercise resistance (i.e., the lack of or the adverse response to exercise on metabolic health). Here, in 39 medication-naive men with prediabetes, we found that exercise-induced alterations in the gut microbiota correlated closely with improvements in glucose homeostasis and insulin sensitivity (clinicaltrials.gov entry NCT03240978). The microbiome of responders exhibited an enhanced capacity for biosynthesis of short-chain fatty acids and catabolism of branched-chain amino acids, whereas those of non-responders were characterized by increased production of metabolically detrimental compounds. Fecal microbial transplantation from responders, but not non-responders, mimicked the effects of exercise on alleviation of insulin resistance in obese mice. Furthermore, a machine-learning algorithm integrating baseline microbial signatures accurately predicted personalized glycemic response to exercise in an additional 30 subjects. These findings raise the possibility of maximizing the benefits of exercise by targeting the gut microbiota.}, }
@article {pmid31784432, year = {2019}, author = {Pai, N and Popov, J and Hill, L and Hartung, E}, title = {Protocol for a double-blind, randomised, placebo-controlled pilot study for assessing the feasibility and efficacy of faecal microbiota transplant in a paediatric Crohn's disease population: PediCRaFT Trial.}, journal = {BMJ open}, volume = {9}, number = {11}, pages = {e030120}, pmid = {31784432}, issn = {2044-6055}, mesh = {Administration, Oral ; Adolescent ; Child ; Child, Preschool ; Colonoscopy/methods ; Crohn Disease/microbiology/*therapy ; Double-Blind Method ; Feasibility Studies ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Pilot Projects ; Research Design ; Treatment Outcome ; }, abstract = {INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory condition with transmural involvement of the gastrointestinal tract. Extraintestinal manifestations are common, and the disease burden on patients and the healthcare system is significant. While treatment options have expanded in recent years, they have mainly focused on dampening the immune response, thus carrying notable risks associated with long-term immunosuppression. Faecal microbiota transplant (FMT) targets inflammatory bowel disease (IBD) by modifying intestinal dysbiosis. Limited adult and paediatric data have demonstrated a favourable response to FMT in IBD; however, no randomised controlled trial has yet been published in paediatrics. This double-blind, randomised, placebo-controlled pilot study will assess feasibility and efficacy outcomes of FMT in a paediatric CD population.<br><br>METHODS AND ANALYSIS: Forty-five patients between the ages of 3 and 17 years, with established CD or IBD unclassified, will be enrolled 2:1 to undergo FMT intervention or placebo control. Participants will undergo a colonoscopic infusion to the terminal ileum at baseline, followed by oral capsules two times per week for 6&#x2009;weeks. Outcomes will be measured throughout the intervention period and 18 weeks of subsequent follow-up. Primary outcomes will assess feasibility, including patient recruitment, sample collection and rates of adverse events. Secondary outcomes will address clinical efficacy, including change in clinical response, change in urine metabolome and change in microbiome.<br><br>ETHICS AND DISSEMINATION: Ethics approval from the local hospital research ethics board was obtained at the primary site (McMaster Children's Hospital, Hamilton), with ethics pending at the secondary site (Centre Hospitalier Universitaire-Sainte-Justine, Montr&#xe9;al). RBX7455 and RBX2660 are human donor-sourced, microbiota-based therapeutic formulations. Both RBX7455 and RBX2660 are currently undergoing clinical trials to support potential US Food and Drug Administration approval. Approval to conduct this paediatric clinical trial was obtained from Health Canada's Biologics and Genetic Therapies Directorate. The results of this trial will be published in peer-reviewed journals and will help inform a large, multicentre trial in the future.<br><br>TRIAL REGISTRATION NUMBER: NCT03378167; pre-results.}, }
@article {pmid31784367, year = {2020}, author = {Mikail, M and O'Doherty, KC and Poutanen, SM and Hota, SS}, title = {Ethical implications of recruiting universal stool donors for faecal microbiota transplantation.}, journal = {The Lancet. Infectious diseases}, volume = {20}, number = {3}, pages = {e44-e49}, doi = {10.1016/S1473-3099(19)30569-9}, pmid = {31784367}, issn = {1474-4457}, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*ethics/*methods ; Humans ; Tissue Donors/*ethics ; }, abstract = {Faecal microbiota transplantation is an effective therapy for recurrent Clostridioides difficile infection, with potential therapeutic applications in other health conditions. As research uncovers potential associations between the intestinal microbiome and various disease states, stool donor screening has become increasingly stringent, leading to low donor acceptance. Many stool banks have opted to recruit universal stool donors, who are encouraged to donate frequently over a prolonged period and whose stool is used to treat multiple patients. However, various ethical concerns arise when recruiting universal stool donors, which need to be addressed to mitigate harm to donors. In this Personal View, we describe the major ethical issues with universal stool banks across six domains: informed consent, privacy, the imposing of restrictions on autonomy, stewardship of microbiome information, financial incentives, and preventing a sense of obligation. We also suggest several priorities for future research that should be pursued to address these crucial issues and develop more donor-centric stool banks.}, }
@article {pmid31784260, year = {2019}, author = {Liu, S and Rezende, RM and Moreira, TG and Tankou, SK and Cox, LM and Wu, M and Song, A and Dhang, FH and Wei, Z and Costamagna, G and Weiner, HL}, title = {Oral Administration of miR-30d from Feces of MS Patients Suppresses MS-like Symptoms in Mice by Expanding Akkermansia muciniphila.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {6}, pages = {779-794.e8}, pmid = {31784260}, issn = {1934-6069}, support = {R01 NS087226/NS/NINDS NIH HHS/United States ; }, mesh = {Administration, Oral ; Akkermansia ; Animals ; *Encephalomyelitis, Autoimmune, Experimental/drug therapy/immunology ; *Fecal Microbiota Transplantation ; Feces ; Gastrointestinal Microbiome/immunology ; Host Microbial Interactions ; Humans ; Lactase/metabolism ; Mice ; Mice, Inbred C57BL ; MicroRNAs/metabolism/*therapeutic use ; Multiple Sclerosis/*drug therapy ; T-Lymphocytes, Regulatory/metabolism ; *Verrucomicrobia/growth &amp; development/immunology/metabolism ; }, abstract = {Fecal transfer from healthy donors is being explored as a microbiome modality. MicroRNAs (miRNAs) have been found to affect the microbiome. Multiple sclerosis (MS) patients have been shown to have an altered gut microbiome. Here, we unexpectedly found that transfer of feces harvested at peak disease from the experimental autoimmune encephalomyelitis (EAE) model of MS ameliorates disease in recipients in a miRNA-dependent manner. Specifically, we show that miR-30d is enriched in the feces of peak EAE and untreated MS patients. Synthetic miR-30d given orally ameliorates EAE through expansion of regulatory T cells (Tregs). Mechanistically, miR-30d regulates the expression of a lactase in Akkermansia muciniphila, which increases Akkermansia abundance in the gut. The expanded Akkermansia in turn increases Tregs to suppress EAE symptoms. Our findings report the mechanistic underpinnings of a miRNA-microbiome axis and suggest that the feces of diseased subjects might be enriched with miRNAs with therapeutic properties.}, }
@article {pmid31782899, year = {2020}, author = {Luber, V and Lutz, M and Abele-Horn, M and Einsele, H and Grigoleit, GU and Mielke, S}, title = {Excretion of Ascaris lumbricoides following reduced-intensity allogeneic hematopoietic stem cell transplantation and consecutive treatment with mebendazole.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {22}, number = {1}, pages = {e13224}, doi = {10.1111/tid.13224}, pmid = {31782899}, issn = {1399-3062}, mesh = {Animals ; Ascariasis/*diagnosis ; Ascaris lumbricoides ; Egypt ; Feces/*parasitology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Mebendazole/*therapeutic use ; Middle Aged ; Multiple Myeloma/parasitology/therapy ; Parasite Egg Count ; Stem Cell Transplantation ; Transplantation Conditioning ; Transplantation, Homologous ; }, abstract = {Here, we present the unique case of a 51-year-old German patient with multiple myeloma excreting Ascaris lumbricoides in his stool five weeks after allogeneic hematopoietic stem cell transplantation. Stool analysis remained negative for the presence of eggs, and there was no eosinophilia in the peripheral blood at any time around stem cell transplantation. The patient was commenced on a three-day treatment with mebendazole, which was well tolerated. No serious interactions with the concomitant post-transplant medication or negative effects on the hematopoiesis were observed, and the myeloma still is in complete remission. To our knowledge, this is the first report on excretion of A lumbricoides in the context of allogeneic stem cell transplantation. The case is remarkable with view to the fact that the parasite has supposedly survived all courses of myeloma treatment including autologous and allogeneic conditioning. Parasitosis with A lumbricoides has a worldwide prevalence of about a billion and is extremely rare in northern Europe. Possibly the patient got infected during a trip to Egypt years before multiple myeloma was diagnosed.}, }
@article {pmid31782606, year = {2020}, author = {Herndon, CC and Wang, YP and Lu, CL}, title = {Targeting the gut microbiota for the treatment of irritable bowel syndrome.}, journal = {The Kaohsiung journal of medical sciences}, volume = {36}, number = {3}, pages = {160-170}, doi = {10.1002/kjm2.12154}, pmid = {31782606}, issn = {2410-8650}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/drug therapy/*microbiology/therapy ; Probiotics/pharmacology ; }, abstract = {Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that affects an estimated 11% of people across the world. IBS patients are one of the largest subgroups seen in gastroenterology clinics, exhibit a lesser quality of life, and take greater use of the healthcare system. The exact etiology of IBS remains uncertain. Alterations in the gut microbiome may characterize apotential mechanism in the pathogenesis of IBS. This hypothesis is paralleled by rodent models in which manipulation of the gut microbiota leads to disturbed physiological functions along the brain-gut axis. Recent research in IBS treatments has redirected its focus towards gu microbiome based therapeutics. In this review, we discuss potential roles of enteric bacteria in the pathogenesis of IBS and its comorbidities. We then explore the manipulation of the enteric microbiota by prebiotics, probiotics, antibiotics, dietary changes, and fecal microbiota transfer. We also discuss the positive and negative effects of these therapeutics on IBS symptoms.}, }
@article {pmid31781020, year = {2019}, author = {Yang, D and Zhao, D and Ali Shah, SZ and Wu, W and Lai, M and Zhang, X and Li, J and Guan, Z and Zhao, H and Li, W and Gao, H and Zhou, X and Yang, L}, title = {The Role of the Gut Microbiota in the Pathogenesis of Parkinson's Disease.}, journal = {Frontiers in neurology}, volume = {10}, number = {}, pages = {1155}, pmid = {31781020}, issn = {1664-2295}, abstract = {It is well-recognized that the gut microbiota (GM) is crucial for gut function, metabolism, and energy cycles. The GM also has effects on neurological outcomes via many mechanisms, such as metabolite production and the gut-brain axis. Emerging evidence has gradually indicated that GM dysbiosis plays a role in several neurological diseases, such as Parkinson's disease (PD), Alzheimer's disease, depression, and multiple sclerosis. Several studies have observed that PD patients generally suffer from gastrointestinal disorders and GM dysbiosis prior to displaying motor symptoms, but the specific link between the GM and PD is not clearly understood. In this review, we aim to summarize what is known regarding the correlation between the GM and PD pathologies, including direct, and indirect evidence.}, }
@article {pmid31780599, year = {2019}, author = {Tamilarasan, AG and Irving, P and Meadows, CI and Goldenberg, S}, title = {Faecal microbiota transplantation for refractory C lostridium difficile infection.}, journal = {BMJ case reports}, volume = {12}, number = {11}, pages = {}, pmid = {31780599}, issn = {1757-790X}, mesh = {Aged ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; }, abstract = {Faecal microbiota transplantation (FMT) has become a part of the treatment algorithm for Clostridium difficile infection (CDI), particularly for recurrent infections when antibiotics have diminishing efficacy. Notably, despite a significant proportion of patients suffering from refractory disease, there is a general lack of evidence describing the use of FMT in this patient cohort. We present here a case of successful treatment of refractory CDI in a patient under critical care.}, }
@article {pmid31780560, year = {2019}, author = {Stein-Thoeringer, CK and Nichols, KB and Lazrak, A and Docampo, MD and Slingerland, AE and Slingerland, JB and Clurman, AG and Armijo, G and Gomes, ALC and Shono, Y and Staffas, A and Burgos da Silva, M and Devlin, SM and Markey, KA and Bajic, D and Pinedo, R and Tsakmaklis, A and Littmann, ER and Pastore, A and Taur, Y and Monette, S and Arcila, ME and Pickard, AJ and Maloy, M and Wright, RJ and Amoretti, LA and Fontana, E and Pham, D and Jamal, MA and Weber, D and Sung, AD and Hashimoto, D and Scheid, C and Xavier, JB and Messina, JA and Romero, K and Lew, M and Bush, A and Bohannon, L and Hayasaka, K and Hasegawa, Y and Vehreschild, MJGT and Cross, JR and Ponce, DM and Perales, MA and Giralt, SA and Jenq, RR and Teshima, T and Holler, E and Chao, NJ and Pamer, EG and Peled, JU and van den Brink, MRM}, title = {Lactose drives Enterococcus expansion to promote graft-versus-host disease.}, journal = {Science (New York, N.Y.)}, volume = {366}, number = {6469}, pages = {1143-1149}, pmid = {31780560}, issn = {1095-9203}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; R21 AG066388/AG/NIA NIH HHS/United States ; KL2 TR001115/TR/NCATS NIH HHS/United States ; R56 AI137269/AI/NIAID NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; T32 AI100851/AI/NIAID NIH HHS/United States ; R01 AI032135/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 CA203950/CA/NCI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; }, mesh = {Aged ; Animals ; Dysbiosis ; Enterococcus/genetics/*growth &amp; development/metabolism ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Graft vs Host Disease/*microbiology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Intestines/microbiology ; Lactose/*metabolism ; Male ; Mice ; Microbiota ; Middle Aged ; RNA, Ribosomal, 16S ; Sequence Analysis, RNA ; Transplantation, Homologous ; }, abstract = {Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.}, }
@article {pmid31779704, year = {2019}, author = {Wang, W and Zhai, S and Xia, Y and Wang, H and Ruan, D and Zhou, T and Zhu, Y and Zhang, H and Zhang, M and Ye, H and Ren, W and Yang, L}, title = {Ochratoxin A induces liver inflammation: involvement of intestinal microbiota.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {151}, pmid = {31779704}, issn = {2049-2618}, mesh = {Animals ; Cecum/immunology/*microbiology ; *Ducks/immunology/microbiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*immunology ; Inflammation/chemically induced/*immunology/*microbiology ; Liver/immunology/*microbiology ; Ochratoxins ; }, abstract = {BACKGROUND: Ochratoxin A (OTA) is a widespread mycotoxin and induces liver inflammation to human and various species of animals. The intestinal microbiota has critical importance in liver inflammation; however, it remains to know whether intestinal microbiota mediates the liver inflammation induced by OTA. Here, we treated ducklings with oral gavage of OTA (235 μg/kg body weight) for 2 weeks. Then, the microbiota in the cecum and liver were analyzed with 16S rRNA sequencing, and the inflammation in the liver was analyzed. To explore the role of intestinal microbiota in OTA-induced liver inflammation, intestinal microbiota was cleared with antibiotics and fecal microbiota transplantation was conducted.<br><br>RESULTS: Here, we find that OTA treatment in ducks altered the intestinal microbiota composition and structure&#xa0;[e.g., increasing the relative abundance of lipopolysaccharides (LPS)-producing Bacteroides], and induced the accumulation of LPS and inflammation in the liver. Intriguingly, in antibiotic-treated ducks, OTA failed to induce these alterations in the liver. Notably, with the fecal microbiota transplantation (FMT) program, in which ducks were colonized with intestinal microbiota from control or OTA-treated ducks, we elucidated the involvement of intestinal microbiota, especially Bacteroides, in liver inflammation induced by OTA.<br><br>CONCLUSIONS: These results highlight the role of gut microbiota in OTA-induced liver inflammation and open a new window for novel preventative or therapeutic intervention for mycotoxicosis.}, }
@article {pmid31777058, year = {2020}, author = {Quraishi, MN and Shaheen, W and Oo, YH and Iqbal, TH}, title = {Immunological mechanisms underpinning faecal microbiota transplantation for the treatment of inflammatory bowel disease.}, journal = {Clinical and experimental immunology}, volume = {199}, number = {1}, pages = {24-38}, pmid = {31777058}, issn = {1365-2249}, support = {EME/13/179/01/DH_/Department of Health/United Kingdom ; }, mesh = {Animals ; Disease Models, Animal ; *Dysbiosis/immunology/microbiology/therapy ; *Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases/immunology/microbiology/therapy ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease that results from a dysregulated immune response against specific environmental triggers in a genetically predisposed individual. Increasing evidence has indicated a causal role for changes in gut microbiota (dysbiosis) contributing to this immune-mediated intestinal inflammation. These mechanisms involve dysregulation of multiple facets of the host immune pathways that are potentially reversible. Faecal microbiota transplantation (FMT) is the transfer of processed stool from a healthy donor into an individual with an illness. FMT has shown promising results in both animal model experiments and clinical studies in IBD in the resolution of intestinal inflammation. The underlying mechanisms, however, are unclear. Insights from these studies have shown interactions between modulation of dysbiosis via changes in abundances of specific members of the gut microbial community and changes in host immunological pathways. Unravelling these causal relationships has promising potential for a translational therapy role to develop targeted microbial therapies and understand the mechanisms that underpin IBD aetiopathogenesis. In this review, we discuss current evidence for the contribution of gut microbiota in the disruption of intestinal immune homeostasis and immunoregulatory mechanisms that are associated with the resolution of inflammation through FMT in IBD.}, }
@article {pmid31775890, year = {2019}, author = {Le Roy, T and Lécuyer, E and Chassaing, B and Rhimi, M and Lhomme, M and Boudebbouze, S and Ichou, F and Haro Barceló, J and Huby, T and Guerin, M and Giral, P and Maguin, E and Kapel, N and Gérard, P and Clément, K and Lesnik, P}, title = {The intestinal microbiota regulates host cholesterol homeostasis.}, journal = {BMC biology}, volume = {17}, number = {1}, pages = {94}, pmid = {31775890}, issn = {1741-7007}, mesh = {Animals ; Cholesterol/*metabolism ; Dyslipidemias/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; *Homeostasis ; Intestines/*microbiology ; Mice ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Management of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. The objective of this study was to investigate how the gut microbiota affects host cholesterol homeostasis at the organism scale.<br><br>RESULTS: We depleted the intestinal microbiota of hypercholesterolemic female Apoe[-/-] mice using broad-spectrum antibiotics. Measurement of plasma cholesterol levels as well as cholesterol synthesis and fluxes by complementary approaches showed that the intestinal microbiota strongly regulates plasma cholesterol level, hepatic cholesterol synthesis, and enterohepatic circulation. Moreover, transplant of the microbiota from humans harboring elevated plasma cholesterol levels to recipient mice induced a phenotype of high plasma cholesterol levels in association with a low hepatic cholesterol synthesis and high intestinal absorption pattern. Recipient mice phenotypes correlated with several specific bacterial phylotypes affiliated to Betaproteobacteria, Alistipes, Bacteroides, and Barnesiella taxa.<br><br>CONCLUSIONS: These results indicate that the intestinal microbiota determines the circulating cholesterol level and may thus represent a novel therapeutic target in the management of dyslipidemia and cardiovascular diseases.}, }
@article {pmid31775486, year = {2019}, author = {Wang, Q and Fu, YW and Wang, YQ and Ai, H and Yuan, FF and Wei, XD and Song, YP}, title = {[Fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {40}, number = {10}, pages = {853-855}, pmid = {31775486}, issn = {0253-2727}, mesh = {Diarrhea/etiology/*therapy ; *Fecal Microbiota Transplantation ; *Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; *Leukemia, Myeloid, Acute ; }, abstract = {Objective: To explore the availability and safety of fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Four acute leukemia patients suffered from refractory diarrhea after allo-HSCT. One of them was refractory intestinal infection, the others were intestinal graft versus host disease. One or two doses of fecal microbiota, 3.4-6.0 U for one dose, were infused via nasal-jejunal tube. The curative effect and side effects were reviewed. Results: Three cases achieved complete remission while 1 was stable disease. The side effects included fever, abdominal pain and diarrhea, which all were Ⅰ grade. Conclusion: Fecal microbiota transplantation was effective and safe for refractory diarrhea after allo-HSCT.}, }
@article {pmid31772709, year = {2019}, author = {Lv, WJ and Wu, XL and Chen, WQ and Li, YF and Zhang, GF and Chao, LM and Zhou, JH and Guo, A and Liu, C and Guo, SN}, title = {The Gut Microbiome Modulates the Changes in Liver Metabolism and in Inflammatory Processes in the Brain of Chronic Unpredictable Mild Stress Rats.}, journal = {Oxidative medicine and cellular longevity}, volume = {2019}, number = {}, pages = {7902874}, pmid = {31772709}, issn = {1942-0994}, mesh = {Animals ; Brain/*pathology ; Chronic Disease ; Depression/*metabolism ; Disease Models, Animal ; Gastrointestinal Microbiome ; Humans ; Inflammation/*metabolism ; Liver/*metabolism/pathology ; Male ; Metabolomics/*methods ; Rats ; Stress, Psychological/*psychology ; }, abstract = {Generally, depression is the result of complex gene-environment interactions. Recent studies have showed that the gut microbiota can affect brain function through the microbiota-gut-brain axis. However, the underlying mechanism of the microbiota and potential influence of depression remain elusive. We aimed to determine how gut microbiome contributes to the process of depression and further influences the host. Chronic unpredictable mild stress (CUMS) is used to establish a depression model. Fecal microbiota transplant (FMT) is applied to illustrate that depression can be transmitted via microbiota, and metabolism of liver analysis is applied to demonstrate further influence to the liver. We also analyzed the astrocyte activation in the brain by immunofluorescence (IF). Here, we show that the structure of the gut microbiome changes markedly after rats undergo CUMS. Notably, we found that the ratio of Lactobacillus to Clostridium can be a vital index for the development of depression. Depression-like behavior can be duplicated through FMT. Moreover, increased zonulin and fatty acid binding protein-2 indicates that gut barrier integrity is broken after FMT. Subsequently, metabolomics shows that liver metabolic disorder occurs and leads to liver coagulative necrosis. In addition, increased inflammatory cytokine expression and higher astrocyte activation indicate an inflammatory process in the brain. These findings suggest that dysbiosis gut microbiome contributes to development of depression and further causes liver metabolic disorders in a way that may be relevant to the Lactobacillus to Clostridium ratio.}, }
@article {pmid31771820, year = {2020}, author = {Gerussi, A and D'Amato, D and Cristoferi, L and O'Donnell, SE and Carbone, M and Invernizzi, P}, title = {Multiple therapeutic targets in rare cholestatic liver diseases: Time to redefine treatment strategies.}, journal = {Annals of hepatology}, volume = {19}, number = {1}, pages = {5-16}, doi = {10.1016/j.aohep.2019.09.009}, pmid = {31771820}, issn = {1665-2681}, mesh = {Abatacept/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Azetidines/therapeutic use ; Benzothiazoles/therapeutic use ; Bezafibrate/therapeutic use ; Chalcones/therapeutic use ; Chenodeoxycholic Acid/analogs &amp; derivatives/therapeutic use ; Cholagogues and Choleretics/*therapeutic use ; Cholangitis, Sclerosing/*drug therapy ; Fecal Microbiota Transplantation ; Fibroblast Growth Factors/analogs &amp; derivatives/therapeutic use ; Gastrointestinal Microbiome ; Humans ; Immunologic Factors/*therapeutic use ; Isoxazoles/therapeutic use ; Janus Kinase Inhibitors/therapeutic use ; Liver Cirrhosis, Biliary/*drug therapy ; Peroxisome Proliferator-Activated Receptors/*agonists ; Propionates/therapeutic use ; Purines/therapeutic use ; Pyrazoles/therapeutic use ; Pyrazolones/therapeutic use ; Pyridones/therapeutic use ; Receptors, Cytoplasmic and Nuclear/*agonists ; Steroids/therapeutic use ; Sulfonamides/therapeutic use ; Tretinoin/therapeutic use ; Ursodeoxycholic Acid/therapeutic use ; Ustekinumab/therapeutic use ; }, abstract = {Primary biliary cholangitis and primary sclerosing cholangitis are rare diseases affecting the bile ducts and the liver. The limited knowledge of their pathogenesis leads to limited therapeutic options. Nevertheless, the landscape of novel therapies for these cholangiopathies is now rapidly changing, providing new treatment opportunities for patients and clinicians involved in their care. The aim of this review is to summarize the evidence of novel molecules under investigation for primary biliary cholangitis and primary sclerosing cholangitis and to discuss how they can potentially change current treatment paradigms.}, }
@article {pmid31769569, year = {2020}, author = {Lee, MSL and Ramakrishna, B and Moss, AC and Gold, HS and Branch-Elliman, W}, title = {Successful treatment of fulminant Clostridioides difficile infection with emergent fecal microbiota transplantation in a patient with acute myeloid leukemia and prolonged, severe neutropenia.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {22}, number = {1}, pages = {e13216}, doi = {10.1111/tid.13216}, pmid = {31769569}, issn = {1399-3062}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; Clostridium Infections/*therapy ; Diarrhea/therapy ; *Fecal Microbiota Transplantation ; Humans ; *Immunocompromised Host ; Leukemia, Myeloid, Acute/*complications/microbiology ; Male ; Neutropenia/*complications/microbiology ; Pseudomonas Infections/drug therapy ; Treatment Outcome ; }, abstract = {We present a patient with acute myeloid leukemia and prolonged, severe neutropenia who developed fulminant Clostridioides difficile infection refractory to medical therapy and was high-risk for surgical intervention. He was treated with fecal microbiota transplantation (FMT) for life-saving cure. The patient had subsequent clinical improvement, however, developed multidrug-resistant Pseudomonas aeruginosa bacteremia 2 days post-procedure. We describe subsequent investigation of this event that found this bacteremia was not related to the donor stool administered during FMT. This case adds to the literature that FMT could be considered in heavily immunocompromised patients with fulminant Clostridioides difficile infection where maximal medical therapy has been ineffective and surgery may carry an excessively high mortality risk.}, }
@article {pmid31768834, year = {2020}, author = {Bowman, JA and Utter, GH}, title = {Evolving Strategies to Manage Clostridium difficile Colitis.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {24}, number = {2}, pages = {484-491}, pmid = {31768834}, issn = {1873-4626}, support = {T32 HS022236/HS/AHRQ HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Bacterial Toxins ; Broadly Neutralizing Antibodies/therapeutic use ; Clostridioides difficile ; Colectomy ; Enterocolitis, Pseudomembranous/diagnosis/*therapy ; *Fecal Microbiota Transplantation ; Fidaxomicin/therapeutic use ; Humans ; Ileostomy ; Risk Factors ; Therapeutic Irrigation ; Vancomycin/*therapeutic use ; }, abstract = {Clostridium difficile infection remains a common nosocomial illness with a significant impact on health care delivery. As molecular phenotyping of this organism has changed our understanding of its transmission and virulence, so too have diagnostic methods and treatment strategies evolved in recent years. The burden of this infection falls predominantly on elderly patients with comorbidities who have recently received antibiotics. Oral or enteral vancomycin is now preferred for first-line antimicrobial treatment across the disease spectrum, including mild-moderate initial cases. Fidaxomicin (a novel macrolide antibiotic), bezlotoxumab (a monoclonal antibody against toxin TcdB), and fecal microbiota transplantation expand the therapeutic armamentarium, particularly for recurrent infection. Operative treatment should be reserved for patients with fulminant infection, and early identification of patients who would benefit from an operation remains a challenge. Less invasive surgical options-such as laparoscopic diverting ileostomy with colonic irrigation-may improve survival and other outcomes relative to total abdominal colectomy and represent an attractive alternative particularly for frail patients.}, }
@article {pmid31768581, year = {2020}, author = {Kikuchi, T and Mimura, K and Ashizawa, M and Okayama, H and Endo, E and Saito, K and Sakamoto, W and Fujita, S and Endo, H and Saito, M and Momma, T and Saze, Z and Ohki, S and Shimada, K and Yoshimura, K and Tsunoda, T and Kono, K}, title = {Characterization of tumor-infiltrating immune cells in relation to microbiota in colorectal cancers.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {69}, number = {1}, pages = {23-32}, pmid = {31768581}, issn = {1432-0851}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Immunological/pharmacology/therapeutic use ; Bacteria/immunology/isolation &amp; purification ; Cohort Studies ; Colectomy ; Colon/immunology/microbiology/pathology ; Colorectal Neoplasms/*immunology/microbiology/therapy ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; Humans ; Intestinal Mucosa/immunology/microbiology/pathology ; Lymphocytes, Tumor-Infiltrating/drug effects/*immunology/metabolism ; Macrophages/drug effects/*immunology/metabolism ; Male ; Middle Aged ; Tumor Escape/drug effects/*immunology ; Tumor Microenvironment/drug effects/immunology ; }, abstract = {BACKGROUND: Several articles have recently reported that certain colon microbiota can improve the efficacy of cancer immunotherapy. To develop new treatment strategies, including immunotherapy for colorectal cancer (CRC), we evaluated the correlations between subpopulations of tumor-infiltrating immune cells (TIICs) and intestinal microbiota in CRC.<br><br>METHODS: Fresh surgically resected specimens, formalin-fixed paraffin-embedded whole tissue samples, and stool samples were collected. TIICs including Tregs, Th17 cells and tumor-associated macrophages (TAMs) in the surgically resected specimens were analyzed using flow cytometry. FOXp3, CD8, CD163, and phosphorylated-STAT1-positive TIICs in the whole tissue samples were analyzed using IHC, and intestinal microbiota in the stool samples was analyzed using 16S metagenome sequencing. TIICs subpopulations in the normal mucosa and tumor samples were evaluated, and the correlations between the TIIC subpopulations and intestinal microbiota were analyzed.<br><br>RESULTS: FOXp3[low]CD45RA[+] Tregs were significantly reduced (p&#x2009;=&#x2009;0.02), FOXp3[low]CD45RA[-] Tregs were significantly increased (p&#x2009;=&#x2009;0.006), and M1 TAMs were significantly reduced in the tumor samples (p&#x2009;=&#x2009;0.03). Bacteroides (phylum Bacteroidetes) and Faecalibacterium (phylum Firmicutes) were increased in the patients with high numbers of Tregs and clearly high distribution of FOXp3[high]CD45RA[-] Tregs, which are the effector Tregs. Faecalibacterium, Ruminococcaceae, Eubacterium (phylum Firmicutes), and Bacteroides were increased in patients with a high distribution of M1 TAMs.<br><br>CONCLUSIONS: The findings of the present study indicate that immune responses to tumors are suppressed in the tumor microenvironment of CRC depending on the increment of Tregs and the reduction of M1 TAMs and that intestinal microbiota might be involved in immunosuppression.}, }
@article {pmid31767915, year = {2019}, author = {Nadatani, Y and Watanabe, T and Suda, W and Nakata, A and Matsumoto, Y and Kosaka, S and Higashimori, A and Otani, K and Hosomi, S and Tanaka, F and Nagami, Y and Kamata, N and Taira, K and Yamagami, H and Tanigawa, T and Hattori, M and Fujiwara, Y}, title = {Gastric acid inhibitor aggravates indomethacin-induced small intestinal injury via reducing Lactobacillus johnsonii.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {17490}, pmid = {31767915}, issn = {2045-2322}, mesh = {Animals ; Disease Models, Animal ; Dysbiosis/*chemically induced/microbiology ; Fecal Microbiota Transplantation ; High-Throughput Nucleotide Sequencing ; Humans ; Indomethacin/administration &amp; dosage/*adverse effects ; Injections, Intraperitoneal ; Intestine, Small/drug effects/*injuries/microbiology ; Lactobacillus johnsonii/drug effects/*isolation &amp; purification/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Proton Pump Inhibitors/administration &amp; dosage/*adverse effects ; Pyrroles/administration &amp; dosage/adverse effects ; RNA, Ribosomal, 16S/genetics ; Rabeprazole/administration &amp; dosage/adverse effects ; Sequence Analysis, DNA ; Sulfonamides/administration &amp; dosage/adverse effects ; }, abstract = {Proton pump inhibitors (PPIs) alter the composition of the intestinal microbiome, exacerbating indomethacin (IND)-induced small intestinal damage. Vonoprazan fumarate inhibits gastric acid secretion using a different mechanism from PPIs. We investigated the effects of both drugs on the intestinal microbiome and IND-induced small intestinal damage. We sought to clarify whether PPI-induced dysbiosis and worsening of the damage were due to a specific drug class effect of PPIs. Rabeprazole administration increased operational taxonomic unit numbers in the small intestines of C57BL/6 J mice, whereas the difference was not significant in the vonoprazan-treated group but exhibited a trend. Permutational multivariate analysis of variance of the unweighted UniFrac distances showed significant differences between vehicle- and vonoprazan- or rabeprazole-treated groups. L. johnsonii was the predominant microbial species, and the population ratio decreased after vonoprazan and rabeprazole administration. The vonoprazan- and rabeprazole-treated groups showed increased IND-induced damage. This high sensitivity to IND-induced damage was evaluated by transplantation with contents from the small intestine of mice treated with either vonoprazan or rabeprazole. Supplementation of L. johnsonii orally in mice treated with rabeprazole and vonoprazan prevented the increase in IND-induced small intestinal damage. In conclusion, both rabeprazole and vonoprazan aggravated NSAID-induced small intestinal injury by reducing the population of L. johnsonii in the small intestine via suppressing gastric acid secretion.}, }
@article {pmid31767028, year = {2019}, author = {Seishima, J and Iida, N and Kitamura, K and Yutani, M and Wang, Z and Seki, A and Yamashita, T and Sakai, Y and Honda, M and Yamashita, T and Kagaya, T and Shirota, Y and Fujinaga, Y and Mizukoshi, E and Kaneko, S}, title = {Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {252}, pmid = {31767028}, issn = {1474-760X}, mesh = {Animals ; Case-Control Studies ; Colitis/etiology/pathology ; Colitis, Ulcerative/drug therapy/*microbiology ; Colon/pathology ; Crohn Disease/microbiology ; Disease Models, Animal ; Drug Therapy, Combination ; Enterococcus faecalis/genetics/*pathogenicity ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Interleukin-10/genetics ; Male ; *Metagenome ; Mice ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Recent metagenomic analyses have revealed dysbiosis of the gut microbiota of ulcerative colitis (UC) patients. However, the impacts of this dysbiosis are not fully understood, particularly at the strain level.<br><br>RESULTS: We perform whole-genome shotgun sequencing of fecal DNA extracts from 13 healthy donors and 16 UC and 8 Crohn's disease (CD) patients. The microbiota of UC and CD patients is taxonomically and functionally divergent from that of healthy donors, with E. faecium being the most differentially abundant species between the two microbial communities. Transplantation of feces from UC or CD patients into Il10[-/-] mice promotes pathological inflammation and cytokine expression in the mouse colon, although distinct cytokine expression profiles are observed between UC and CD. Unlike isolates derived from healthy donors, E. faecium isolates from the feces of UC patients, along with E. faecium strain ATCC 19434, promotes colitis and colonic cytokine expression. Inflammatory E. faecium strains, including ATCC 19434 and a UC-derived strain, cluster separately from commercially available probiotic strains based on whole-genome shotgun sequencing analysis. The presence of E. faecium in fecal samples is associated with large disease extent and the need for multiple medications in UC patients.<br><br>CONCLUSIONS: E. faecium strains derived from UC patients display an inflammatory genotype that causes colitis.}, }
@article {pmid31766624, year = {2019}, author = {Sari, G and van de Garde, MDB and van Schoonhoven, A and Voermans, JJC and van der Eijk, AA and de Man, RA and Boonstra, A and Vanwolleghem, T and Pas, SD}, title = {Hepatitis E Virus Shows More Genomic Alterations in Cell Culture than In Vivo.}, journal = {Pathogens (Basel, Switzerland)}, volume = {8}, number = {4}, pages = {}, pmid = {31766624}, issn = {2076-0817}, abstract = {Hepatitis E Virus (HEV) mutations following ribavirin treatment have been associated with treatment non-response and viral persistence, but spontaneous occurring genomic variations have been less well characterized. We here set out to study the HEV genome composition in 2 patient sample types and 2 infection models. Near full HEV genome Sanger sequences of serum- and feces-derived HEV from two chronic HEV genotype 3 (gt3) patients were obtained. In addition, viruses were sequenced after in vitro or in vivo expansion on A549 cells or a humanized mouse model, respectively. We show that HEV acquired 19 nucleotide mutations, of which 7 nonsynonymous amino acids changes located in Open Reading Frame 1 (ORF1), ORF2, and ORF3 coding regions, after prolonged in vitro culture. In vivo passage resulted in selection of 8 nucleotide mutations with 2 altered amino acids in the X domain and Poly-proline region of ORF1. Intra-patient comparison of feces- and serum-derived HEV gt3 of two patients showed 7 and 2 nucleotide mutations with 2 and 0 amino acid changes, respectively. Overall, the number of genomic alterations was up to 1.25× per 1000 nucleotides or amino acids in in vivo samples, and up to 2.84× after in vitro expansion of the same clinical HEV strain. In vitro replication of a clinical HEV strain is therefore associated with more mutations, compared to the minor HEV genomic alterations seen after passage of the same strain in an immune deficient humanized mouse; as well as in feces and blood of 2 immunosuppressed chronically infected HEV patients. These data suggest that HEV infected humanized mice more closely reflect the HEV biology seen in solid organ transplant recipients.}, }
@article {pmid31764154, year = {2020}, author = {Jerkic, M and Gagnon, S and Rabani, R and Ward-Able, T and Masterson, C and Otulakowski, G and Curley, GF and Marshall, J and Kavanagh, BP and Laffey, JG}, title = {Human Umbilical Cord Mesenchymal Stromal Cells Attenuate Systemic Sepsis in Part by Enhancing Peritoneal Macrophage Bacterial Killing via Heme Oxygenase-1 Induction in Rats.}, journal = {Anesthesiology}, volume = {132}, number = {1}, pages = {140-154}, doi = {10.1097/ALN.0000000000003018}, pmid = {31764154}, issn = {1528-1175}, support = {//Canadian Institutes for Health Research/International ; }, mesh = {Animals ; Heme Oxygenase-1/*metabolism ; Humans ; Macrophages, Peritoneal/*metabolism ; Male ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*metabolism ; Rats ; Rats, Sprague-Dawley ; Sepsis/*therapy ; *Umbilical Cord ; }, abstract = {BACKGROUND: Mesenchymal stromal cells have therapeutic potential in sepsis, but the mechanism of action is unclear. We tested the effects, dose-response, and mechanisms of action of cryopreserved, xenogeneic-free human umbilical cord mesenchymal stromal cells in a rat model of fecal peritonitis, and examined the role of heme oxygenase-1 in protection.<br><br>METHODS: Separate in vivo experiments evaluated mesenchymal stromal cells in fecal sepsis, established dose response (2, 5, and 10 million cells/kg), and the role of heme oxygenase-1 in mediating human umbilical cord-derived mesenchymal stromal/stem cell effects. Ex vivo studies utilized pharmacologic blockers and small inhibitory RNAs to evaluate mechanisms of mesenchymal stromal cell enhanced function in (rodent, healthy and septic human) macrophages.<br><br>RESULTS: Human umbilical cord mesenchymal stromal cells reduced injury and increased survival (from 48%, 12 of 25 to 88%, 14 of 16, P = 0.0033) in fecal sepsis, with dose response studies demonstrating that 10 million cells/kg was the most effective dose. Mesenchymal stromal cells reduced bacterial load and peritoneal leukocyte infiltration (from 9.9 &#xb1; 3.1 &#xd7; 10/ml to 6.2 &#xb1; 1.8 &#xd7; 10/ml, N = 8 to 10 per group, P < 0.0001), and increased heme oxygenase-1 expression in peritoneal macrophages, liver, and spleen. Heme oxygenase-1 blockade abolished the effects of mesenchymal stromal cells (N = 7 or 8 per group). Mesenchymal stromal cells also increased heme oxygenase-1 expression in macrophages from healthy donors and septic patients. Direct ex vivo upregulation of macrophage heme oxygenase-1 enhanced macrophage function (phagocytosis, reactive oxygen species production, bacterial killing). Blockade of lipoxin A4 production in mesenchymal stromal cells, and of prostaglandin E2 synthesis in mesenchymal stromal cell/macrophage cocultures, prevented upregulation of heme oxygenase-1 in macrophages (from 9.6 &#xb1; 5.5-fold to 2.3 &#xb1; 1.3 and 2.4 &#xb1; 2.3 respectively, P = 0.004). Knockdown of heme oxygenase-1 production in macrophages ablated mesenchymal stromal cell enhancement of macrophage phagocytosis.<br><br>CONCLUSIONS: Human umbilical cord mesenchymal stromal cells attenuate systemic sepsis by enhancing peritoneal macrophage bacterial killing, mediated partly via upregulation of peritoneal macrophage heme oxygenase-1. Lipoxin A4 and prostaglandin E2 play key roles in the mesenchymal stromal cell and macrophage interaction.}, }
@article {pmid31761117, year = {2020}, author = {Albuhairi, S and Rachid, R}, title = {Novel Therapies for Treatment of Food Allergy.}, journal = {Immunology and allergy clinics of North America}, volume = {40}, number = {1}, pages = {175-186}, doi = {10.1016/j.iac.2019.09.007}, pmid = {31761117}, issn = {1557-8607}, mesh = {Animals ; Antibodies, Monoclonal, Humanized/therapeutic use ; Biological Therapy/*trends ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Food Hypersensitivity/*therapy ; Humans ; Microbiota/*immunology ; Omalizumab/therapeutic use ; Vaccines, DNA/*immunology ; }, abstract = {Food allergy prevalence has increased over the past 2 decades and is estimated to affect 8% of children and 4% to 10% of adults. There is an unmet need to evaluate new therapeutic modalities that may decrease the risk of food-induced anaphylaxis and improve patients' quality of life. Oral, epicutaneous, and sublingual food immunotherapies have different safety and efficacy profiles, and their long-term outcome and applicability are unclear. Food allergy trials are currently evaluating different biologics (given as monotherapy or adjunct to immunotherapy), modified food proteins, DNA vaccines, and fecal microbiota transplantation.}, }
@article {pmid31760385, year = {2019}, author = {Yu, F and Han, W and Zhan, G and Li, S and Jiang, X and Wang, L and Xiang, S and Zhu, B and Yang, L and Luo, A and Hua, F and Yang, C}, title = {Abnormal gut microbiota composition contributes to the development of type 2 diabetes mellitus in db/db mice.}, journal = {Aging}, volume = {11}, number = {22}, pages = {10454-10467}, pmid = {31760385}, issn = {1945-4589}, mesh = {Animals ; Diabetes Mellitus, Type 2/*microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {It is well recognized that type 2 diabetes mellitus (T2DM) is an age-related metabolic disease, emerging gradually as a major global health burden that has gained public attention. Meanwhile, increasing attention is paid to the crucial role of gut microbiota in the pathogenesis and therapeutic mechanisms of metabolic disorders, especially T2DM. In this study, we used C57 BL/KS db/db male mice as a T2DM murine model. We found that the β-diversity and relative abundances of gut bacteria were obviously altered in db/db mice, associated with a significant increase in Verrucomicrobia at six levels (phylum, class, order, etc.) and family S24-7 and a significant decrease in Bacteroidaceae at family, genus, and species levels, as well as Prevotellaceae at family and genus levels. Furthermore, fecal bacteria from db/db and m/m mice transplanted into pseudo-germ-free mice showed a significant change in the metabolic parameters, including the body weight, fasting blood glucose, fluid and food intake, and alterations in the composition of the gut microbiota. Taken together, these findings suggest that abnormalities in the composition of the gut microbiota might contribute to the development of T2DM and that potential therapeutic strategies improving gut microbiota might provide beneficial effects for individuals with T2DM and age-related glucose intolerance.}, }
@article {pmid31759038, year = {2020}, author = {Chen, Y and Zhang, L and Hong, G and Huang, C and Qian, W and Bai, T and Song, J and Song, Y and Hou, X}, title = {Probiotic mixtures with aerobic constituent promoted the recovery of multi-barriers in DSS-induced chronic colitis.}, journal = {Life sciences}, volume = {240}, number = {}, pages = {117089}, doi = {10.1016/j.lfs.2019.117089}, pmid = {31759038}, issn = {1879-0631}, mesh = {Animals ; *Bacteria, Aerobic ; Cell Membrane Permeability ; Chronic Disease ; Colitis/*chemically induced/*drug therapy/pathology ; Dextran Sulfate ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Intestinal Mucosa/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Probiotics/administration &amp; dosage/*therapeutic use ; Tight Junctions ; }, abstract = {AIMS: Gut microbiota has been closely linked to the mucosal immune and been regarded as a reliable target for intestinal inflammation. This study aimed to explore the therapeutic roles of probiotic mixtures of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis with (quadruple probiotics, P-qua) or without (triple probiotics, P-tri) aerobic Bacillus cereus in colitis, focusing on the multiple barrier functions.<br><br>MATERIALS AND METHODS: Chronic colitis was induced by dextran sulfate sodium (DSS) in C57BL/6 mice. The probiotic mixtures P-qua or P-tri was gavage administrated respectively, while fecal microbiota transplantation (FMT) as a positive control. The intestinal inflammation and functions of multiple barriers were assessed, including the mucus barrier, epithelial barrier and endothelial barrier known as gut-vascular barrier (GVB). Altered composition and diversity in gut microbiota were observed via sequencing analysis.<br><br>KEY FINDINGS: Both P-qua and P-tri relieved the intestinal inflammation and improved the functions of multiple barriers with increased integrity of mucous layer, enhanced transepithelial electrical resistance, declined epithelial and endothelial permeability to macromolecules in DSS-colitis. Aerobe-contained P-qua revealed a more active role in barrier recovering relative to P-tri, while FMT as a positive control seemed to get better results than pure probiotics. Indeed, P-qua was effective in rebuilding the structure and diversity of gut flora in DSS-colitis, especially increased abundance of Bifidobacterium, Akkermansia, Lactobacillus and Bacteroides.<br><br>SIGNIFICANCE: Aerobe-contained P-qua was a powerful adjuvant therapy for chronic colitis, via restoring the intestinal microflora and recovering the multi-barriers in the inflamed gut.}, }
@article {pmid31758248, year = {2020}, author = {Schiffmann, L and Kostev, K and Kalder, M}, title = {Fecal and urinary incontinence are major problems associated with rectal cancer.}, journal = {International journal of colorectal disease}, volume = {35}, number = {1}, pages = {35-40}, pmid = {31758248}, issn = {1432-1262}, mesh = {Aged ; Fecal Incontinence/diagnosis/epidemiology/*etiology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Kaplan-Meier Estimate ; Male ; Rectal Neoplasms/*complications ; Time Factors ; Urinary Incontinence/diagnosis/epidemiology/*etiology ; }, abstract = {BACKGROUND: The goal of this retrospective cohort study was to analyze the incidence of urinary incontinence (UI) and fecal incontinence (FI) within 5 years of diagnosis in patients with rectal carcinoma (RC) and within 5 years of a randomly selected visit date in non-cancer controls followed in general practices in Germany.<br><br>METHODS: Patients who had received an initial RC diagnosis at one of 1262 general practices in Germany between January 2008 and December 2017 were included in this study (index date). Patients without cancer were matched (1:1) to RC patients by sex, age, index year, and practice. The main outcome of the study was the incidence of UI and FI within 5 years of RC diagnosis.<br><br>RESULTS: The study included 3249 individuals with RC and 3249 individuals without cancer (mean age 66.5 years, 57.3% males). Within 5 years of the index date, 8.6% of RC patients and 1.3% of patients without cancer received a FI diagnosis, and 16.7% of RC patients and 5.3% of patients without cancer received a UI diagnosis. Overall, RC was positively associated with both FI (hazard ratio (HR) 8.39, 95% CI 5.50-12.81) and UI (HR 3.59, 95% CI 2.91-4.44). These findings were corroborated in the different age subgroups.<br><br>CONCLUSION: In accordance with the literature, we confirmed that RC is significantly associated with fecal and urinary incontinence. However, it appears that the awareness of this fact needs to be improved among general practitioners since our data show lower percentages of fecal and urinary incontinence diagnoses compared with the percentages for specialized centers reported in the literature.}, }
@article {pmid31756956, year = {2019}, author = {Cheng, H and Guan, X and Chen, D and Ma, W}, title = {The Th17/Treg Cell Balance: A Gut Microbiota-Modulated Story.}, journal = {Microorganisms}, volume = {7}, number = {12}, pages = {}, pmid = {31756956}, issn = {2076-2607}, support = {31902282//National Natural Science Foundation of China/ ; 2018-NK-125//Qinghai province Major R&amp;D and Transformation Project/ ; }, abstract = {The intestinal tract of vertebrates is normally colonized with a remarkable number of commensal microorganisms that are collectively referred to as gut microbiota. Gut microbiota has been demonstrated to interact with immune cells and to modulate specific signaling pathways involving both innate and adaptive immune processes. Accumulated evidence suggests that the imbalance of Th17 and Treg cells is associated with the development of many diseases. Herein, we emphatically present recent findings to show how specific gut microbiota organisms and metabolites shape the balance of Th17 and Treg cells. We also discuss the therapeutic potential of fecal microbiota transplantation (FMT) in diseases caused by the imbalance of Th17 and Treg cells.}, }
@article {pmid31751317, year = {2019}, author = {Bajaj, JS and Salzman, N and Acharya, C and Takei, H and Kakiyama, G and Fagan, A and White, MB and Gavis, EA and Holtz, ML and Hayward, M and Nittono, H and Hylemon, PB and Cox, IJ and Williams, R and Taylor-Robinson, SD and Sterling, RK and Matherly, SC and Fuchs, M and Lee, H and Puri, P and Stravitz, RT and Sanyal, AJ and Ajayi, L and Le Guennec, A and Atkinson, RA and Siddiqui, MS and Luketic, V and Pandak, WM and Sikaroodi, M and Gillevet, PM}, title = {Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis.}, journal = {JCI insight}, volume = {4}, number = {24}, pages = {}, pmid = {31751317}, issn = {2379-3708}, support = {UL1 TR002649/TR/NCATS NIH HHS/United States ; /BHF_/British Heart Foundation/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; /DH_/Department of Health/United Kingdom ; I01 CX001076/CX/CSRD VA/United States ; I01 BX000197/BX/BLRD VA/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Capsules ; Cognition/*physiology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Hepatic Encephalopathy/etiology/microbiology/physiopathology/*therapy ; Humans ; Liver Cirrhosis/complications/microbiology/physiopathology/*therapy ; Male ; Middle Aged ; Placebos/administration &amp; dosage ; Treatment Outcome ; United Kingdom ; Young Adult ; }, abstract = {BACKGROUNDHepatic encephalopathy (HE) is associated with poor outcomes. A prior randomized, pilot trial demonstrated safety after oral capsular fecal microbial transplant (FMT) in HE, with favorable changes in microbial composition and cognition. However, microbial functional changes are unclear. The aim of this study was to determine the effect of FMT on the gut-brain axis compared with placebo, using microbial function based on bile acids (BAs), inflammation (serum IL-6, LPS-binding protein [LBP]), and their association with EncephalApp.METHODSTwenty cirrhotic patients were randomized 1:1 into groups that received 1-time FMT capsules from a donor enriched in Lachnospiraceae and Ruminococcaceae or placebo capsules, with 5-month follow-up for safety outcomes. Stool microbiota and BA; serum IL-6, BA, and LBP; and EncephalApp were analyzed at baseline and 4 weeks after FMT/placebo. Correlation networks among microbiota, BAs, EncephalApp, IL-6, and LBP were performed before/after FMT.RESULTSFMT-assigned participants had 1 HE recurrence and 2 unrelated infections. Six placebo-assigned participants developed negative outcomes. FMT, but not placebo, was associated with reduced serum IL-6 and LBP and improved EncephalApp. FMT-assigned participants demonstrated higher deconjugation and secondary BA formation in feces and serum compared with baseline. No change was seen in placebo. Correlation networks showed greater complexity after FMT compared with baseline. Beneficial taxa, such as Ruminococcaceae, Verrucomicrobiaceae, and Lachnospiraceae, were correlated with cognitive improvement and decrease in inflammation after FMT. Fecal/serum secondary/primary ratios and PiCRUST secondary BA pathways did not increase in participants who developed poor outcomes.CONCLUSIONGut microbial function in cirrhosis is beneficially affected by capsular FMT, with improved inflammation and cognition. Lower secondary BAs in FMT recipients could select for participants who develop negative outcomes.TRIAL REGISTRATIONClinicaltrials.gov NCT03152188.FUNDINGNational Center for Advancing Translational Sciences NIH grant R21TR002024, VA Merit Review grant 2I0CX001076, the United Kingdom National Institute for Health Research Biomedical Facility at Imperial College London, the British Heart Foundation, Wellcome Trust, and King's College London.}, }
@article {pmid31750921, year = {2020}, author = {Basson, AR and Gomez-Nguyen, A and Menghini, P and Buttó, LF and Di Martino, L and Aladyshkina, N and Osme, A and LaSalla, A and Fischer, D and Ezeji, JC and Erkkila, HL and Brennan, CJ and Lam, M and Rodriguez-Palacios, A and Cominelli, F}, title = {Human Gut Microbiome Transplantation in Ileitis Prone Mice: A Tool for the Functional Characterization of the Microbiota in Inflammatory Bowel Disease Patients.}, journal = {Inflammatory bowel diseases}, volume = {26}, number = {3}, pages = {347-359}, pmid = {31750921}, issn = {1536-4844}, support = {T35 DK111373/DK/NIDDK NIH HHS/United States ; T32 DK083251/DK/NIDDK NIH HHS/United States ; P01 DK091222/DK/NIDDK NIH HHS/United States ; P30 DK097948/DK/NIDDK NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; R01 DK055812/DK/NIDDK NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; F32 DK117585/DK/NIDDK NIH HHS/United States ; R21 DK118373/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Colony Count, Microbial ; Crohn Disease/*therapy ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Ileitis/*therapy ; Male ; Mice ; RNA, Ribosomal, 16S/genetics ; Remission Induction ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a lifelong digestive disease characterized by periods of severe inflammation and remission. To our knowledge, this is the first study showing a variable effect on ileitis severity from human gut microbiota isolated from IBD donors in remission and that of healthy controls in a mouse model of IBD.<br><br>METHODS: We conducted a series of single-donor intensive and nonintensive fecal microbiota transplantation (FMT) experiments using feces from IBD patients in remission and healthy non-IBD controls (N = 9 donors) in a mouse model of Crohn's disease (CD)-like ileitis that develops ileitis in germ-free (GF) conditions (SAMP1/YitFC; N = 96 mice).<br><br>RESULTS: Engraftment studies demonstrated that the microbiome of IBD in remission could have variable effects on the ileum of CD-prone mice (pro-inflammatory, nonmodulatory, or anti-inflammatory), depending on the human donor. Fecal microbiota transplantation achieved a 95% &#xb1; 0.03 genus-level engraftment of human gut taxa in mice, as confirmed at the operational taxonomic unit level. In most donors, microbiome colonization abundance patterns remained consistent over 60 days. Microbiome-based metabolic predictions of GF mice with Crohn's or ileitic-mouse donor microbiota indicate that chronic amino/fatty acid (valine, leucine, isoleucine, histidine; linoleic; P < 1e-15) alterations (and not bacterial virulence markers; P > 0.37) precede severe ileitis in mice, supporting their potential use as predictors/biomarkers in human CD.<br><br>CONCLUSION: The gut microbiome of IBD remission patients is not necessarily innocuous. Characterizing the inflammatory potential of each microbiota in IBD patients using mice may help identify the patients' best anti-inflammatory fecal sample for future use as an anti-inflammatory microbial autograft during disease flare-ups.}, }
@article {pmid31750259, year = {2019}, author = {Lin, DM and Koskella, B and Ritz, NL and Lin, D and Carroll-Portillo, A and Lin, HC}, title = {Transplanting Fecal Virus-Like Particles Reduces High-Fat Diet-Induced Small Intestinal Bacterial Overgrowth in Mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {348}, pmid = {31750259}, issn = {2235-2988}, mesh = {Animals ; Bacterial Load ; Bacteriophages/isolation &amp; purification/ultrastructure ; Clostridioides difficile ; Diet, High-Fat/*adverse effects ; Disease Models, Animal ; Dysbiosis/*therapy ; Enterocolitis, Pseudomembranous/microbiology/therapy ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Intestine, Small/*microbiology ; Metagenomics/methods ; Mice ; RNA, Ribosomal, 16S ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is an effective tool for treating Clostridium difficile infection in the setting of dysbiosis of the intestinal microbiome. FMT for other forms of human disorders linked to dysbiosis have been less effective. The fecal microbiota contains a high density of virus-like particles (VLP), up to 90% of which are bacteriophages, thought to have a role in regulating gut bacterial populations. We hypothesized that transplantation of the phage-containing fecal VLP fraction may reduce bacterial density in the dysbiotic setting of small intestinal bacterial overgrowth (SIBO). In an experiment using fecal transplantation, we compared the effect of the fecal VLP fraction (bacteria removed) against "Whole" FMT (bacteria intact) on the ileal microbiome. Recipients were either treated with a 30-day high-fat diet (HFD) as a model of dysbiosis to induce SIBO or were on a standard diet (SD). We observed that transplantation of fecal VLPs from donors on a HFD was sufficient to alter the ileal microbiota, but the effect was dependent on diet of the recipient. In recipients on a HFD, ileal bacterial density was reduced. In recipients on a SD, the ileal microbiome transitioned toward the composition associated with a HFD. In both recipient groups, transplantation of fecal VLP fraction alone produced the same outcome as whole FMT. Neither treatment altered expression of antimicrobial peptides. These findings demonstrated a potential role of VLPs, likely phages, for modifying the gut microbiome during dysbiosis.}, }
@article {pmid31749279, year = {2020}, author = {Quaranta, G and Fancello, G and Ianiro, G and Graffeo, R and Gasbarrini, A and Cammarota, G and Sanguinetti, M and Masucci, L}, title = {Laboratory handling practice for faecal microbiota transplantation.}, journal = {Journal of applied microbiology}, volume = {128}, number = {3}, pages = {893-898}, doi = {10.1111/jam.14522}, pmid = {31749279}, issn = {1365-2672}, mesh = {Bacterial Load ; Biological Specimen Banks/standards ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome ; Humans ; Laboratories/*standards ; Specimen Handling/*methods ; Workflow ; }, abstract = {AIMS: Faecal microbiota transplantation (FMT) consists of the infusion of faeces from a healthy donor to the gastrointestinal tract of a recipient patient to treat disease associated with alterations in gut microbiota. The objective of this article was to describe laboratory workflow of an FMT laboratory to provide tips for preparing the faecal suspensions to be infused.<br><br>METHODS AND RESULTS: Twenty-stool solutions obtained from ten donors were prepared using two different protocols: magnet plate emulsion (MPE) and Seward Stomacher[TM] Emulsion (SSE). We evaluated parameters such as preparation time, handiness, and aerobic and anaerobic microbial count. For three donors, we monitored bacterial counts after defrosting at different time-points. MPE requires more time than SSE. In terms of microbial load, both methods showed similar values, with small and statistically differences (P&#xa0;&#x2264;&#xa0;0&#xb7;05) regarding anaerobes in favour of SSE. Frozen aliquots showed the same bacterial load values after defrosting.<br><br>CONCLUSION: Although both methods allow an easy and available preparation of a stool suspension, SSE seems more suitable, particularly for stool banking. Aerobic and anaerobic species are preserved with both protocols; and safety for laboratory operators is guaranteed.<br><br>In recent years, FMT has become a fascinating and interesting subject. Nevertheless, there are no real guidelines describing laboratory facilities and procedures. This paper aims to be a useful and simple guide to increase the number FMT centres as much possible.}, }
@article {pmid31745820, year = {2019}, author = {Cheng, YW and Fischer, M}, title = {Treatment of Severe and Fulminnant Clostridioides difficile Infection.}, journal = {Current treatment options in gastroenterology}, volume = {17}, number = {4}, pages = {524-533}, pmid = {31745820}, issn = {1092-8472}, abstract = {PURPOSE OF REVIEW: This article will review current management strategies for severe and fulminant Clostridioides difficile infection (CDI).<br><br>RECENT FINDINGS: Clostridioides difficile is the most common nosocomial cause of infectious diarrhea. With the rise of hypervirulent strains of CDI, almost 8% of patients hospitalized with CDI are afflicted with severe CDI (SCDI) or fulminant CDI (FCDI). A significant proportion of these patients do not respond to recommended anti-CDI antibiotic therapy such as oral vancomycin and fidaxomicin. Current recommendations suggest that patients with refractory CDI should proceed to colectomy or diverting loop ileostomy with colonic lavage. However, both of these surgical interventions result in high rates of post-surgical mortality approaching 30%. Fecal microbiota transplantation (FMT) is a promising therapy that is recommended in recurrent CDI. Recent studies have found that FMT can safely produce cure rates between 70 and 90% in patients with SCDI and FCDI, while significantly decreasing rates of CDI-related mortality and colectomy. A patient population likely to benefit the most from FMT is elderly patients due to their increased risk for CDI, treatment failure, and high comorbidity burden that may preclude surgical intervention. FMT should be considered in patients with SCDI or FCDI particularly when traditional anti-CDI antibiotics are ineffective.}, }
@article {pmid31745030, year = {2019}, author = {Pushpanathan, P and Mathew, GS and Selvarajan, S and Seshadri, KG and Srikanth, P}, title = {Gut microbiota and its mysteries.}, journal = {Indian journal of medical microbiology}, volume = {37}, number = {2}, pages = {268-277}, doi = {10.4103/ijmm.IJMM_19_373}, pmid = {31745030}, issn = {1998-3646}, mesh = {Animals ; Biodiversity ; Diabetes Mellitus, Type 2/etiology/metabolism/therapy ; Diet ; Disease Management ; *Disease Susceptibility ; Exercise ; Female ; *Gastrointestinal Microbiome ; Humans ; Life Style ; Male ; Obesity/etiology/metabolism/therapy ; Research ; }, abstract = {Gut microbiota are microorganisms that inhabit the gut; they coexist peacefully with the host, thereby contributing to the health and well-being of individuals. Bacteroidetes and Firmicutes largely dominate the gut microbial flora. The intestinal flora promotes intestinal mucosal integrity, provides essential nutrients such as vitamins and enzymes, protects the body against pathogens and produces antimicrobial peptides such as defensins, C-type lectins, cathelicidins, they also play an active role in the innate and adaptive immune system. Gut microbial flora plays an active role in the synthesis of short-chain fatty acids such as butyrate, propionate and acetate. Gut microbiota also plays a significant role in the cognitive and behavioural functions of the host. A balanced gut microbiota shifts to dysbiosis, due to intake of high fat or sugar or other factors like sedentary lifestyle. The dysbiosis of the gut results in increased permeability, endotoxaemic, insulin resistant, systemic inflammation, adiposity and metabolic disorders such as type 2 diabetes mellitus, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, irritable bowel disorder, colorectal cancer, etc. A prudent lifestyle modification, added on with use of probiotics and prebiotic restore the normal flora of the gut, especially in patients with Clostridium difficle-associated diarrhoea, inflammatory bowel syndrome, liver disease and colon cancer. Faecal microbial transplant is an important therapeutic tool in many illness related with the gut. Thereby, understanding the gut microbial signatures in various diseases yields various novel therapeutic targets. Human gut microbiota has a prognostic, diagnostic and therapeutic potential which is recognised worldwide.}, }
@article {pmid31744592, year = {2020}, author = {Debes, KP and Evdina, NA and Laigaard, A and Larsen, JM and Zachariassen, LF and Hansen, CHF and Hansen, AK}, title = {Betamethasone Treatment for Atopic Dermatitis in Gut Microbiota Transplanted Mice.}, journal = {Comparative medicine}, volume = {70}, number = {1}, pages = {6-15}, pmid = {31744592}, issn = {2769-819X}, mesh = {Animals ; Betamethasone/*administration &amp; dosage ; Dermatitis, Atopic/pathology/*therapy ; Ear/pathology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects ; Male ; *Mice ; Pregnancy ; Random Allocation ; }, abstract = {Gut microbiota composition correlates strongly with essential disease parameters in the oxazolone-induced mouse model for atopic dermatitis. The phenotype of this model can be transferred to germ-free mice with a gut microbiota transplant to achieve high and low responding mice. Therefore, the production of high responding mice through gut microbiota transplantation may be seen as a tool to reduce group sizes or increase power in intervention studies by increasing effect size. We sought to determine whether high responding mice respond to a common treatment in the same way as low responding mice. We hypothesized that while high responding mice would exhibit a higher clinical score than low responding mice before treatment, the clinical parameters would be similar in both groups after betamethasone treatment. Dermatitis was induced with oxazolone in barrier bred Swiss Webster mice, and a high responding and a low responding donor was selected based upon clinical and pathologic scores, as confirmed by monitoring a range of ear tissue cytokines. Feces from these donors were transplanted to pregnant germ-free Swiss Webster dams, and subsequently to their offspring. Although the overall effect of betamethasone on the clinical dermatitis score and ear thickness was rather small, the high responding recipients had significantly higher clinical dermatitis score and ear thickness than the low responding recipients before treatment, and these differences vanished after betamethasone treatment. We conclude that high responding recipients can be treated to a clinical level comparable with the low responding recipients.}, }
@article {pmid31742291, year = {2019}, author = {Chen, P and Hei, M and Kong, L and Liu, Y and Yang, Y and Mu, H and Zhang, X and Zhao, S and Duan, J}, title = {One water-soluble polysaccharide from Ginkgo biloba leaves with antidepressant activities via modulation of the gut microbiome.}, journal = {Food &amp; function}, volume = {10}, number = {12}, pages = {8161-8171}, doi = {10.1039/c9fo01178a}, pmid = {31742291}, issn = {2042-650X}, mesh = {Animals ; Antidepressive Agents/*administration &amp; dosage ; Bacteria/classification/drug effects/genetics/isolation &amp; purification ; Behavior, Animal/drug effects ; Depression/*drug therapy/metabolism/microbiology ; Dopamine ; Gastrointestinal Microbiome/*drug effects ; Ginkgo biloba/*chemistry ; Hindlimb Suspension ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Plant Extracts/*administration &amp; dosage ; Plant Leaves/chemistry ; Polysaccharides/*administration &amp; dosage ; Serotonin/metabolism ; }, abstract = {Depression, a mental illness characterized by persistent feeling of sadness and loss of interest, has been a serious health problem worldwide. Manipulation of the microbiota by probiotics and prebiotics represents a novel emerging strategy for the treatment of various psychiatric disorders such as major depressive disorders. Here, we show that one water-soluble polysaccharide from Ginkgo biloba leaves (GPS) reduced stress-induced depression and reversed gut dysbiosis. Similar to the antidepressant paroxetine, GPS significantly reduced the immobility times in the tail suspension test (TST) and forced swimming test (FST) and anxiety-like behavior in the open field test (OFT). Consistent with the improvement of depression-like behavior above, GPS mice had elevated serotonin and dopamine levels in multiple brain regions including the hippocampus, cerebral cortex and olfactory bulb, relative to unpredictable chronic mild stress (UCMS) treatment mice. GPS treatment could alleviate the stress-induced reduction in the density of serotonin-positive and dopamine-positive cells. Fecal microbiome transplant (FMT) combined with antibiotic treatment showed that the anti-depressant activity of GPS had a causal relationship with intestinal microbes. By performing a pyrosequencing-based analysis of bacterial 16S rRNA (V3 + V4 region) in fecal of the mice, the results showed that GPS reversed depression-associated gut dysbiosis and increased the richness of Lactobacillus species which has been proven to be a path to relieve depression. Our results demonstrated that the polysaccharide from Ginkgo biloba leaves might be a promising pharmacotherapeutic candidate for treating depression.}, }
@article {pmid31742290, year = {2019}, author = {Fu, A and Mo, Q and Wu, Y and Wang, B and Liu, R and Tang, L and Zeng, Z and Zhang, X and Li, W}, title = {Protective effect of Bacillus amyloliquefaciens against Salmonella via polarizing macrophages to M1 phenotype directly and to M2 depended on microbiota.}, journal = {Food &amp; function}, volume = {10}, number = {12}, pages = {7653-7666}, doi = {10.1039/c9fo01651a}, pmid = {31742290}, issn = {2042-650X}, mesh = {Animals ; Bacillus amyloliquefaciens/*physiology ; Bacteria/classification/genetics/isolation &amp; purification ; Cell Polarity/drug effects ; Humans ; Macrophage Activation/drug effects ; Macrophages/drug effects/*immunology ; Male ; Mice, Inbred C57BL ; *Microbiota/drug effects ; Phagocytosis/drug effects ; Probiotics/*administration &amp; dosage ; Salmonella Infections/immunology/microbiology/*prevention &amp; control ; Salmonella typhimurium/*drug effects/physiology ; }, abstract = {Bacillus amyloliquefaciens SC06 (BaSC06), a potential probiotic, plays a positive role in animal growth performance and immune function. The aim of the present study was to investigate the protective effect of BaSC06 against Salmonella infection and its association with macrophage polarization. C57BL/6 mice were fed with or without a BaSC06-containing diet before Salmonella enterica Typhimurium (ST) challenge. Results showed that BaSC06 had a protective effect against ST inoculation and induced both M1 and M2 macrophage polarization in the cecum. An in vitro co-culture model demonstrated that BaSC06 promoted M1 polarization directly, and thus increased the phagocytosis and bactericidal activity against ST. In addition, adoptive transfer of bone marrow-derived macrophages (BMDMs) stimulated by BaSC06 significantly decreased the counts of ST in the spleen. Furthermore, 16S rRNA-based analysis of cecal content showed that BaSC06 significantly increased the proportion of Verrucomicrobia and decreased Bacterodetes. Transplantation of the fecal microbiota from BaSC06-treated animals promoted M2 macrophage polarization in the cecum and significantly relieved inflammation caused by ST. In conclusion, BaSC06 polarized macrophages to the M1 type directly resulting in excellent bactericidal activity. Meanwhile, the microbiota modified by BaSC06 can induce M2 polarization which ameliorates the inflammation caused by ST.}, }
@article {pmid31739374, year = {2019}, author = {Schulte, LA and Schäfer, A and Steding, K and Rauschek, L and Klaus, J}, title = {[Acceptance of fecal microbiota transfer among patients with chronic inflammatory bowel diseases in a highly specialized outpatient department: a questionnaire-based survey].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {57}, number = {11}, pages = {1291-1297}, doi = {10.1055/a-1010-6920}, pmid = {31739374}, issn = {1439-7803}, mesh = {Fecal Microbiota Transplantation/adverse effects/*methods ; Feces ; Humans ; Inflammatory Bowel Diseases/*therapy ; Microbiota ; *Patient Acceptance of Health Care ; Perception ; Surveys and Questionnaires ; }, abstract = {Recently, research in the treatment of inflammatory bowel diseases has become increasingly focused on fecal microbiota transfer (FMT) due to increasing evidence of its possible benefits. Still, there are doubts about this method, because there is contradicting evidence regarding its effectiveness and the possible side effects are not well known. Furthermore, the majority of patients are not open to this procedure. We performed a questionnaire-based survey amongst 302 patients with an inflammatory bowel disease that received treatment in our specialized outpatient clinic to determine the factors relevant for acceptance or rejection of fecal microbiota transfer as a possible treatment for Crohn's disease or ulcerative colitis. Our data supports the hypothesis that a lack of information about FMT is a key factor for hypothetical acceptance of this method (68 % of pre-informed participants vs. 30 % of not pre-informed participants would accept FMT as treatment, p < 0.001), and, therefore, it highlights patient education as a possible intervention to improve acceptance. The main concern regarding FMT was possible transmission of infections (ranked first by 98 participants). The most accepted method to perform FMT was application via oral capsule (44 % of participants).}, }
@article {pmid31737727, year = {2019}, author = {Krajicek, E and Bohm, M and Sagi, S and Fischer, M}, title = {Fulminant Clostridium difficile Infection Cured by Fecal Microbiota Transplantation in a Bone Marrow Transplant Recipient With Critical Neutropenia.}, journal = {ACG case reports journal}, volume = {6}, number = {8}, pages = {e00198}, pmid = {31737727}, issn = {2326-3253}, abstract = {Clostridium difficile infection is the most prevalent health care-associated infection. Treatment relies on antimicrobial therapy with mounting evidence supporting fecal microbiota transplant (FMT) in refractory cases. Cohort studies have documented the safety of FMT in immunocompromised patients. However, the safety of FMT in patients with critically low (<500/μL) absolute neutrophil count is unknown. Currently, in severely immunocompromised bone marrow or solid organ transplant recipients, FMT is delayed until normalization of absolute neutrophil count. We present a patient with absolute neutropenia in whom sequential FMTs were safely and successfully administered, resulting in cure of fulminant C. difficile infection.}, }
@article {pmid31728525, year = {2020}, author = {Terveer, EM and van Gool, T and Ooijevaar, RE and Sanders, IMJG and Boeije-Koppenol, E and Keller, JJ and Bart, A and Kuijper, EJ and , }, title = {Human Transmission of Blastocystis by Fecal Microbiota Transplantation Without Development of Gastrointestinal Symptoms in Recipients.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {71}, number = {10}, pages = {2630-2636}, pmid = {31728525}, issn = {1537-6591}, mesh = {*Blastocystis/genetics ; *Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Feces ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Patients with multiple recurrent Clostridioides difficile infections (rCDI) are treated with fecal microbiota transplantation (FMT), using feces provided by healthy donors. Blastocystis colonization of donors is considered an exclusion criterion, whereas its pathogenicity is still under debate.<br><br>METHODS: The introduction of molecular screening for Blastocystis sp. at our stool bank identified 2 donors with prior negative microscopies but positive polymerase chain reactions (PCRs). Potential transmission of Blastocystis sp. to patients was assessed on 16 fecal patient samples, pre- and post-FMT, by PCR and subtype (ST) analyses. In addition, clinical outcomes for the treatment of rCDI (n = 31), as well as the development of gastrointestinal symptoms, were assessed.<br><br>RESULTS: There was 1 donor who carried Blastocystis ST1, and the other contained ST3. All patients tested negative for Blastocystis prior to FMT. With a median diagnosis at 20.5 days after FMT, 8 of 16 (50%) patients developed intestinal colonization with Blastocystis, with identical ST sequences as their respective donors. Blastocystis-containing fecal suspensions were used to treat 31 rCDI patients, with an FMT success rate of 84%. This success rate was not statistically different from patients transferred with Blastocystis sp.-negative donor feces (93%, 76/82). Patients transferred with Blastocystis sp.-positive donor feces did not report any significant differences in bowel complaints in the first week, after 3 weeks, or in the months following FMT.<br><br>CONCLUSIONS: We demonstrated the first transmission of Blastocystis ST1 and ST3 from donors to patients by FMT. This did not result in gastrointestinal symptomatology or have any significant effect on rCDI treatment outcomes.}, }
@article {pmid31728280, year = {2019}, author = {Cui, M and Xiao, H and Li, Y and Zhang, S and Dong, J and Wang, B and Zhu, C and Jiang, M and Zhu, T and He, J and Wang, H and Fan, S}, title = {Sexual Dimorphism of Gut Microbiota Dictates Therapeutics Efficacy of Radiation Injuries.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {6}, number = {21}, pages = {1901048}, pmid = {31728280}, issn = {2198-3844}, support = {R01 AT005076/AT/NCCIH NIH HHS/United States ; R01 GM063075/GM/NIGMS NIH HHS/United States ; }, abstract = {Accidental or iatrogenic ionizing radiation exposure precipitates acute and chronic radiation injuries. The traditional paradigm of mitigating radiotherapy-associated adverse side effects has ignored the gender-specific dimorphism of patients' divergent responses. Here, the effects of sexual dimorphism on curative efficiencies of therapeutic agents is examined in murine models of irradiation injury. Oral gavage of simvastatin ameliorates radiation-induced hematopoietic injury and gastrointestinal tract dysfunction in male mice, but adversely deteriorates these radiation syndromes in female animals. In a sharp contrast, feeding animals with high-fat diet (HFD) elicites explicitly contrary results. High-throughput sequencing of microbial 16S rRNA, host miRNA, and mRNA shows that simvastatin or HFD administration preventes radiation-altered enteric bacterial taxonomic structure, preserves miRNA expression profile, and reprogrammes the spectrum of mRNA expression in small intestines of male or female mice, respectively. Notably, faecal microbiota transplantation of gut microbes from opposite sexual donors abrogates the curative effects of simvastatin or HFD in respective genders of animals. Together, these findings demonstrate that curative efficiencies of therapeutic strategies mitigating radiation toxicity might be dependent on the gender of patients, thus simvastatin or HFD might be specifically useful for fighting against radiation toxicity in a sex-dependent fashion partly based on sex-distinct gut microbiota composition in preclinical settings.}, }
@article {pmid31727807, year = {2019}, author = {Frederick, E}, title = {Bacterial toxin linked to severe alcoholic liver disease.}, journal = {Science (New York, N.Y.)}, volume = {366}, number = {6467}, pages = {784}, doi = {10.1126/science.366.6467.784}, pmid = {31727807}, issn = {1095-9203}, mesh = {Animals ; *Bacterial Toxins ; Bacteriophages ; *Enterococcus faecalis/isolation &amp; purification/pathogenicity ; Feces/microbiology ; Humans ; *Liver Cirrhosis, Alcoholic/microbiology/pathology ; Liver Transplantation ; Mice ; Perforin ; Prognosis ; Severity of Illness Index ; }, }
@article {pmid31726747, year = {2019}, author = {Fukui, H}, title = {Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?.}, journal = {Diseases (Basel, Switzerland)}, volume = {7}, number = {4}, pages = {}, pmid = {31726747}, issn = {2079-9721}, abstract = {Accumulating evidence supports that gut dysbiosis may relate to various liver diseases. Alcoholics with high intestinal permeability had a decrease in the abundance of Ruminnococcus. Intestinal dysmotility, increased gastric pH, and altered immune responses in addition to environmental and genetic factors are likely to cause alcohol-associated gut microbial changes. Alcohol-induced dysbiosis may be associated with gut barrier dysfunction, as microbiota and their products modulate barrier function by affecting epithelial pro-inflammatory responses and mucosal repair functions. High levels of plasma endotoxin are detected in alcoholics, in moderate fatty liver to advanced cirrhosis. Decreased abundance of Faecalibacterium prausnitzii, an anti-inflammatory commensal, stimulating IL-10 secretion and inhibiting IL-12 and interferon-γ expression. Proteobacteria, Enterobacteriaceae, and Escherichia were reported to be increased in NAFLD (nonalcoholic fatty liver disease) patients. Increased abundance of fecal Escherichia to elevated blood alcohol levels in these patients and gut microbiota enriched in alcohol-producing bacteria produce more alcohol (alcohol hypothesis). Some undetermined pathological sequences related to gut dysbiosis may facilitate energy-producing and proinflammatory conditions for the progression of NAFLD. A shortage of autochthonous non-pathogenic bacteria and an overgrowth of potentially pathogenic bacteria are common findings in cirrhotic patients. The ratio of the amounts of beneficial autochthonous taxa (Lachnospiraceae + Ruminococaceae + Veillonellaceae + Clostridiales Incertae Sedis XIV) to those of potentially pathogenic taxa (Enterobacteriaceae + Bacteroidaceae) was low in those with early death and organ failure. Cirrhotic patients with decreased microbial diversity before liver transplantation were more likely to develop post-transplant infections and cognitive impairment related to residual dysbiosis. Patients with PSC had marked reduction of bacterial diversity. Enterococcus and Lactobacillus were increased in PSC patients (without liver cirrhosis.) Treatment-naive PBC patients were associated with altered composition and function of gut microbiota, as well as a lower level of diversity. As serum anti-gp210 antibody has been considered as an index of disease progression, relatively lower species richness and lower abundance of Faecalibacterium spp. in gp210-positive patients are interesting. The dysbiosis-induced altered bacterial metabolites such as a hepatocarcinogenesis promotor DCA, together with a leaky gut and bacterial translocation. Gut protective Akkermansia and butyrate-producing genera were decreased, while genera producing-lipopolysaccharide were increased in early hepatocellular carcinoma (HCC) patients.}, }
@article {pmid31726029, year = {2019}, author = {Ng, KM and Aranda-Díaz, A and Tropini, C and Frankel, MR and Van Treuren, W and O'Loughlin, CT and Merrill, BD and Yu, FB and Pruss, KM and Oliveira, RA and Higginbottom, SK and Neff, NF and Fischbach, MA and Xavier, KB and Sonnenburg, JL and Huang, KC}, title = {Recovery of the Gut Microbiota after Antibiotics Depends on Host Diet, Community Context, and Environmental Reservoirs.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {5}, pages = {650-665.e4}, pmid = {31726029}, issn = {1934-6069}, support = {DP2 OD006466/OD/NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; R01 DK101674/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacterial Load/*drug effects ; Bacteroides/classification/*growth &amp; development/isolation &amp; purification ; Biodiversity ; Ciprofloxacin/pharmacology ; Diet ; Female ; Gastrointestinal Microbiome/*drug effects ; Gastrointestinal Tract/drug effects/*microbiology ; Germ-Free Life ; Humans ; Male ; Mice ; Rifaximin/pharmacology ; Streptomycin/pharmacology ; }, abstract = {Antibiotics alter microbiota composition and increase infection susceptibility. However, the generalizable effects of antibiotics on and the contribution of environmental variables to gut commensals remain unclear. To address this, we tracked microbiota dynamics with high temporal and taxonomic resolution during antibiotic treatment in a controlled murine system by isolating variables such as diet, treatment history, and housing co-inhabitants. Human microbiotas were remarkably resilient and recovered during antibiotic treatment, with transient dominance of resistant Bacteroides and taxa-asymmetric diversity reduction. In certain cases, in vitro sensitivities were not predictive of in vivo responses, underscoring the significance of host and community context. A fiber-deficient diet exacerbated microbiota collapse and delayed recovery. Species replacement through cross housing after ciprofloxacin treatment established resilience to a second treatment. Single housing drastically disrupted recovery, highlighting the importance of environmental reservoirs. Our findings highlight deterministic microbiota adaptations to perturbations and the translational potential for modulating diet, sanitation, and microbiota composition during antibiotics.}, }
@article {pmid31725010, year = {2020}, author = {Caggiano, G and Cosola, C and Di Leo, V and Gesualdo, M and Gesualdo, L}, title = {Microbiome modulation to correct uremic toxins and to preserve kidney functions.}, journal = {Current opinion in nephrology and hypertension}, volume = {29}, number = {1}, pages = {49-56}, doi = {10.1097/MNH.0000000000000565}, pmid = {31725010}, issn = {1473-6543}, mesh = {Dysbiosis/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Kidney/*physiopathology ; Renal Insufficiency, Chronic/microbiology/physiopathology/*therapy ; Toxins, Biological/urine ; Uremia/urine ; }, abstract = {PURPOSE OF REVIEW: The association between dysbiosis and CKD is well established. This review focuses on the current understanding of microbiome, in normal individuals and CKD patients, in order to hypothesize how to correct uremic toxins levels and preserve the renal function and reduce associated comorbidities. Here we discuss our current opinion on microbiome modulation in order to manage the CKD-associated dysbiosis.<br><br>RECENT FINDINGS: Emerging evidence confirms the role of gut microbiome in the progression of CKD. In this scenario, the need is felt to set up multifaceted approaches for dysbiosis management. Among many strategies able to improve gut wellness, a crucial approach is represented by the functional nutrition. At the same time, drug-based treatments show significant results in microbiome modulation. Furthermore, we examine here the potentialities of fecal microbiome transplantation (FMT) in CKD, an approach currently applied in Clostridium difficile infection.<br><br>SUMMARY: The gut microbiome plays a pivotal role in the pathophysiology of CKD. The vicious cycle triggered by kidney function decline leads to gut dysbiosis. Considering the gut microbiome as a therapeutic target in CKD, multiple approaches aimed at its modulation should be envisioned to preserve kidney function. Dietary interventions and pharmacological strategies are able to improve microbiome dysbiosis, oxidative stress and fibrosis. Additionally, FMT could represent a promising novel therapy in the management of CKD-associated dysbiosis.}, }
@article {pmid31723038, year = {2019}, author = {Kundu, P and Lee, HU and Garcia-Perez, I and Tay, EXY and Kim, H and Faylon, LE and Martin, KA and Purbojati, R and Drautz-Moses, DI and Ghosh, S and Nicholson, JK and Schuster, S and Holmes, E and Pettersson, S}, title = {Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice.}, journal = {Science translational medicine}, volume = {11}, number = {518}, pages = {}, doi = {10.1126/scitranslmed.aau4760}, pmid = {31723038}, issn = {1946-6242}, mesh = {Animals ; Butyrates/metabolism ; Doublecortin Domain Proteins ; *Fecal Microbiota Transplantation ; Fibroblast Growth Factors/metabolism ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Hippocampus/physiology ; Intestines/anatomy &amp; histology/growth &amp; development ; Liver/metabolism ; Longevity/*physiology ; Male ; Metabolome ; Mice, Inbred C57BL ; Microtubule-Associated Proteins/metabolism ; Neurogenesis/*physiology ; Neurons/metabolism ; Neuropeptides/metabolism ; Phenotype ; Proton Magnetic Resonance Spectroscopy ; }, abstract = {The gut microbiota evolves as the host ages, yet the effects of these microbial changes on host physiology and energy homeostasis are poorly understood. To investigate these potential effects, we transplanted the gut microbiota of old or young mice into young germ-free recipient mice. Both groups showed similar weight gain and skeletal muscle mass, but germ-free mice receiving a gut microbiota transplant from old donor mice unexpectedly showed increased neurogenesis in the hippocampus of the brain and increased intestinal growth. Metagenomic analysis revealed age-sensitive enrichment in butyrate-producing microbes in young germ-free mice transplanted with the gut microbiota of old donor mice. The higher concentration of gut microbiota-derived butyrate in these young transplanted mice was associated with an increase in the pleiotropic and prolongevity hormone fibroblast growth factor 21 (FGF21). An increase in FGF21 correlated with increased AMPK and SIRT-1 activation and reduced mTOR signaling. Young germ-free mice treated with exogenous sodium butyrate recapitulated the prolongevity phenotype observed in young germ-free mice receiving a gut microbiota transplant from old donor mice. These results suggest that gut microbiota transplants from aged hosts conferred beneficial effects in responsive young recipients.}, }
@article {pmid31722059, year = {2020}, author = {Bossa, F and Biscaglia, G and Valvano, MR and Costantino, G and Lauria, A and Clemente, R and Ferracane, C and Shahini, E and Mendolaro, M and Grossi, L and Mazzuoli, S and Rispo, A and Pranzo, G and Sebkova, L and Tursi, A and Miranda, A and Patturelli, M and Spagnuolo, R and Ricciardelli, C and Sgarro, C and Paese, P and Inserra, G and Azzarone, A and Nardone, O and Fries, W and Buccianti, N and Privitera, AC and Principi, MB and Cappello, M and Guglielmi, FW and Romano, M and Riegler, G and Fanigliulo, L and Melina, R and Andriulli, A}, title = {Real-Life Effectiveness and Safety of Golimumab and Its Predictors of Response in Patients with Ulcerative Colitis.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {6}, pages = {1767-1776}, doi = {10.1007/s10620-019-05904-z}, pmid = {31722059}, issn = {1573-2568}, mesh = {Adult ; Antibodies, Monoclonal/administration &amp; dosage/adverse effects/*therapeutic use ; Cohort Studies ; Colitis, Ulcerative/*therapy ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Golimumab is a new anti-TNF-alpha monoclonal antibody for patients with ulcerative colitis.<br><br>AIMS: To assess the short- and long-term effectiveness and safety of golimumab in daily clinical practice and to identify predictors of response.<br><br>METHODS: Consecutive patients treated with golimumab in 22 Italian centers were enrolled. Clinical, laboratory, and endoscopic data were prospectively collected before and during treatment. A subgroup of patients completed a questionnaire to assess personal satisfaction with a golimumab autoinjector system.<br><br>RESULTS: A total of 196 patients were included. After 3&#xa0;months, 130 patients were responders (66.3%) and showed significant reductions in mean partial, total, and endoscopic Mayo scores and in mean ESR, C-reactive protein, and fecal calprotectin levels (p&#x2009;<&#x2009;0.001). Multivariate analysis revealed that a higher total Mayo score (p&#x2009;<&#x2009;0.001, OR 1.5, 95% CI 1.2-1.8) and na&#xef;ve status to anti-TNF-alpha (p&#x2009;=&#x2009;0.015, OR 3.0, 95% CI 1.2-7.5) were predictive of a favorable response. Seventy-seven (39.3%) of the 130 responders maintained a response at month 12 of therapy. There were 17 adverse events, 28 patients needed hospitalization, and 15 patients underwent surgery. Self-administration of the drug was appreciated by most patients.<br><br>CONCLUSIONS: The efficacy and safety of golimumab in daily clinical practice were confirmed for the short- and long-term treatment of patients with active ulcerative colitis. Patients na&#xef;ve to the anti-TNF-alpha monoclonal antibody and those with a higher total Mayo score were more likely to respond to golimumab.}, }
@article {pmid31719078, year = {2019}, author = {Quraishi, MNN and Yalchin, M and Blackwell, C and Segal, J and Sharma, N and Hawkey, P and McCune, V and Hart, AL and Gaya, D and Ives, NJ and Magill, L and Loi, S and Hewitt, C and Gerasimidis, K and Loman, NJ and Hansen, R and McMullan, C and Mathers, J and Quince, C and Crees, N and Iqbal, T}, title = {STOP-Colitis pilot trial protocol: a prospective, open-label, randomised pilot study to assess two possible routes of faecal microbiota transplant delivery in patients with ulcerative colitis.}, journal = {BMJ open}, volume = {9}, number = {11}, pages = {e030659}, pmid = {31719078}, issn = {2044-6055}, support = {MR/M50161X/1/MRC_/Medical Research Council/United Kingdom ; MR/M501621/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Aged ; Clinical Protocols ; Colitis, Ulcerative/*therapy ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; Outcome Assessment, Health Care ; Pilot Projects ; Prospective Studies ; United Kingdom ; Young Adult ; }, abstract = {INTRODUCTION: Imbalance of the gut microbiome is key to the pathogenesis of ulcerative colitis (UC). Faecal microbiota transplant (FMT) is the transfer of homogenised and filtered faeces from a healthy individual to the gastrointestinal tract of a patient with disease. Published datasets show a positive signal for the use of FMT to treat UC, but the optimal route and dose of FMT remain unanswered.<br><br>METHODS AND ANALYSIS: This prospective, multi-centre open-label, randomised pilot study will assess two possible routes of FMT delivery, via the nasogastric (NG) route or by delivery to the COLON, in 30 patients with active UC recruited from three sites in the UK. Stool will be collected from healthy screened donors, processed, frozen and stored under a Medicines and Healthcare products Regulatory Agency (MHRA) "specials" manufacturing licence held at the University of Birmingham Microbiome Treatment Centre. Thawed FMT samples will be administered to patients either via eight nasogastric infusions given initially over 4 days starting on the day of randomisation, and then again for 4 days in week 4 for foregut delivery (total of 240 g of stool) or via one colonoscopic infusion followed by seven weekly enemas according to the hindgut protocol (total of 360 g of stool). Patients will be followed up weekly for 8 weeks, and then at 12 weeks. The aims of this pilot study are (1) to determine which FMT administration route (NG or COLON) should be investigated in a randomised double-blind, placebo-controlled trial and (2) to determine if a full randomised controlled trial is feasible. The primary outcome will be a composite assessment of both qualitative and quantitative data based on efficacy (clinical response), acceptability and safety. At the end of the pilot study, decisions will be made regarding the feasibility of a full randomised double-blind, placebo-controlled trial and, if deemed feasible, which route of administration should be used in such a study.<br><br>ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the East Midlands-Nottingham Research Ethics Committee (REC 17/EM/0274). At the end of the study, findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN74072945.}, }
@article {pmid31715298, year = {2020}, author = {Yuille, S and Mackay, WG and Morrison, DJ and Tedford, MC}, title = {Drivers of Clostridioides difficile hypervirulent ribotype 027 spore germination, vegetative cell growth and toxin production in vitro.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {26}, number = {7}, pages = {941.e1-941.e7}, doi = {10.1016/j.cmi.2019.11.004}, pmid = {31715298}, issn = {1469-0691}, mesh = {Acetates/*pharmacology ; Animals ; Bacterial Toxins/genetics/*metabolism ; Bacteriological Techniques ; Chlorocebus aethiops ; Clostridioides difficile/growth &amp; development/metabolism/pathogenicity/*physiology ; Gene Expression Regulation, Bacterial ; Humans ; Hydrogen-Ion Concentration ; Ribotyping ; Spores, Bacterial/growth &amp; development/physiology ; Vero Cells ; Virulence Factors/*genetics ; }, abstract = {OBJECTIVES: Clostridioides difficile infection (CDI) is a considerable healthcare and economic burden worldwide. Faecal microbial transplant remains the most effective treatment for CDI, but is not at the present time the recommended standard of care. We hereby investigate which factors derived from a healthy gut microbiome might constitute the colonization resistance barrier (CRB) in the gut, inhibiting CDI.<br><br>METHODS: CRB drivers pH, short chain fatty acid (SCFA), and oxidation-reduction potential (ORP) were investigated in&#xa0;vitro using C.&#xa0;difficile NAP1/BI/027. Readouts for inhibitory mechanisms included germination, growth, toxin production and virulence gene expression. pH ranges (3-7.6), SCFA concentrations (25-200 mM) and ORP (-300 to 200 mV) were manipulated in brain heart infusion broth cultures under anaerobic conditions to assess the inhibitory action of these mechanisms.<br><br>RESULTS: A pH&#xa0;<&#xa0;5.3 completely inhibited C.&#xa0;difficile growth to optical density (OD) 0.019 vs. 1.19 for control pH 7.5. Toxin production was reduced to 25 units vs. 3125 units for pH 7.6 (1 in 5 dilutions). Virulence gene expression reduced by 150-fold compared with pH 7.6 (p&#xa0;<&#xa0;0.05). Germination and proliferation of spores below pH 6.13 yielded an average OD of 0.006 vs. 0.99 for control. SCFA were potent regulators of toxin production at 25 mM and above (p&#xa0;<&#xa0;0.05). Acetate significantly inhibited toxin production to 25 units independent of OD (0.8733) vs. control (OD 0.6 and toxin titre 3125) (p&#xa0;<&#xa0;0.05). ORP did not impact C.&#xa0;difficile growth.<br><br>CONCLUSIONS: This study highlights the critical role that pH has in the CRB, regulating CDI in&#xa0;vitro and that SCFA can regulate C.&#xa0;difficile function independent of pH.}, }
@article {pmid31714965, year = {2019}, author = {Severyn, CJ and Brewster, R and Andermann, TM}, title = {Microbiota modification in hematology: still at the bench or ready for the bedside?.}, journal = {Blood advances}, volume = {3}, number = {21}, pages = {3461-3472}, pmid = {31714965}, issn = {2473-9537}, support = {KL2 TR001083/TR/NCATS NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; T32 DK098132/DK/NIDDK NIH HHS/United States ; KL2 TR003143/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {Clinical Decision-Making ; Combined Modality Therapy ; Disease Management ; Disease Susceptibility ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Hematologic Neoplasms/complications/etiology/therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; Host-Pathogen Interactions ; Humans ; Infections/diagnosis/etiology/therapy ; *Microbiota ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*complications/diagnosis/therapy ; Probiotics/therapeutic use ; Translational Research, Biomedical ; Transplantation, Homologous ; }, abstract = {Growing evidence suggests that human microbiota likely influence diverse processes including hematopoiesis, chemotherapy metabolism, and efficacy, as well as overall survival in patients with hematologic malignancies and other cancers. Both host genetic susceptibility and host-microbiota interactions may impact cancer risk and response to treatment; however, microbiota have the potential to be uniquely modifiable and accessible targets for treatment. Here, we focus on strategies to modify microbiota composition and function in patients with cancer. First, we evaluate the use of fecal microbiota transplant to restore microbial equilibrium following perturbation by antibiotics and chemotherapy, and as a treatment of complications of hematopoietic stem cell transplantation (HSCT), such as graft-versus-host disease and colonization with multidrug-resistant organisms. We then address the potential use of both probiotics and dietary prebiotic compounds in targeted modulation of the microbiota intended to improve outcomes in hematologic diseases. With each type of therapy, we highlight the role that abnormal, or dysbiotic, microbiota play in disease, treatment efficacy, and toxicity and evaluate their potential promise as emerging strategies for microbiota manipulation in patients with hematologic malignancies and in those undergoing HSCT.}, }
@article {pmid31712445, year = {2019}, author = {Sobhani, I and Bergsten, E and Couffin, S and Amiot, A and Nebbad, B and Barau, C and de'Angelis, N and Rabot, S and Canoui-Poitrine, F and Mestivier, D and Pédron, T and Khazaie, K and Sansonetti, PJ}, title = {Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {48}, pages = {24285-24295}, pmid = {31712445}, issn = {1091-6490}, support = {R01 AI108682/AI/NIAID NIH HHS/United States ; R01 CA264048/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cohort Studies ; Colorectal Neoplasms/*genetics/*microbiology ; DNA Methylation ; Dysbiosis/genetics/microbiology/pathology ; *Epigenesis, Genetic ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Gene Expression Regulation ; Germ-Free Life ; Humans ; Intestinal Mucosa/metabolism/pathology ; Male ; Mice, Inbred C3H ; Promoter Regions, Genetic ; RNA, Ribosomal, 16S ; }, abstract = {Sporadic colorectal cancer (CRC) is a result of complex interactions between the host and its environment. Environmental stressors act by causing host cell DNA alterations implicated in the onset of cancer. Here we investigate the stressor ability of CRC-associated gut dysbiosis as causal agent of host DNA alterations. The epigenetic nature of these alterations was investigated in humans and in mice. Germ-free mice receiving fecal samples from subjects with normal colonoscopy or from CRC patients were monitored for 7 or 14 wk. Aberrant crypt foci, luminal microbiota, and DNA alterations (colonic exome sequencing and methylation patterns) were monitored following human feces transfer. CRC-associated microbiota induced higher numbers of hypermethylated genes in murine colonic mucosa (vs. healthy controls' microbiota recipients). Several gene promoters including SFRP1,2,3, PENK, NPY, ALX4, SEPT9, and WIF1 promoters were found hypermethylated in CRC but not in normal tissues or effluents from fecal donors. In a pilot study (n = 266), the blood methylation levels of 3 genes (Wif1, PENK, and NPY) were shown closely associated with CRC dysbiosis. In a validation study (n = 1,000), the cumulative methylation index (CMI) of these genes was significantly higher in CRCs than in controls. Further, CMI appeared as an independent risk factor for CRC diagnosis as shown by multivariate analysis that included fecal immunochemical blood test. Consequently, fecal bacterial species in individuals with higher CMI in blood were identified by whole metagenomic analysis. Thus, CRC-related dysbiosis induces methylation of host genes, and corresponding CMIs together with associated bacteria are potential biomarkers for CRC.}, }
@article {pmid31711971, year = {2019}, author = {Seekatz, AM}, title = {Development of an alternative animal model to investigate host-microbe interactions.}, journal = {EBioMedicine}, volume = {50}, number = {}, pages = {7-8}, pmid = {31711971}, issn = {2352-3964}, support = {K01 DK111794/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Inflammatory Bowel Diseases/*therapy ; Rats ; }, }
@article {pmid31700231, year = {2019}, author = {Hadjivasilis, A and Tsioutis, C and Michalinos, A and Ntourakis, D and Christodoulou, DK and Agouridis, AP}, title = {New insights into irritable bowel syndrome: from pathophysiology to treatment.}, journal = {Annals of gastroenterology}, volume = {32}, number = {6}, pages = {554-564}, pmid = {31700231}, issn = {1108-7471}, abstract = {Irritable bowel syndrome (IBS) is the most common reason to visit a gastroenterologist. IBS was believed to be a functional disease, but many possible pathophysiologic mechanisms can now explain the symptoms. IBS patients are classified into subtypes according to their predominant bowel habit, based on the Rome IV criteria. These include diarrhea-predominant and constipation-predominant IBS, as well as the mixed type, a combination of the two. Usually, IBS treatment is based on the predominant symptoms, with many options for each subtype. A new promising treatment option, fecal microbiota transplantation, seems to have beneficial effects on IBS. However, treating the pathophysiological causative agent responsible for the symptoms is an emerging approach. Therefore, before the appropriate therapeutic option is chosen for treating IBS, a clinical evaluation of its pathophysiology should be performed.}, }
@article {pmid31699731, year = {2019}, author = {Alhifany, AA and Almutairi, AR and Almangour, TA and Shahbar, AN and Abraham, I and Alessa, M and Alnezary, FS and Cheema, E}, title = {Comparing the efficacy and safety of faecal microbiota transplantation with bezlotoxumab in reducing the risk of recurrent Clostridium difficile infections: a systematic review and Bayesian network meta-analysis of randomised controlled trials.}, journal = {BMJ open}, volume = {9}, number = {11}, pages = {e031145}, pmid = {31699731}, issn = {2044-6055}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Antibodies, Monoclonal/*therapeutic use ; Bayes Theorem ; Broadly Neutralizing Antibodies/*therapeutic use ; Clostridium Infections/physiopathology/*therapy ; Diarrhea/physiopathology ; *Fecal Microbiota Transplantation ; Humans ; Network Meta-Analysis ; Recurrence ; Risk ; Treatment Outcome ; }, abstract = {OBJECTIVES: The risk of recurrent Clostridium difficile infections (RCDIs) is high when treated with standard antibiotics therapy (SAT) alone. It is suggested that the addition of faecal microbiota transplantation (FMT) or bezlotoxumab after SAT reduces the risk of RCDI. In the absence of head-to-head randomised controlled trials (RCTs), this review attempts to compare the efficacy and safety of bezlotoxumab with FMT in reducing the risk of RCDI in hospitalised patients.<br><br>DESIGN: A systematic review and Bayesian network meta-analysis.<br><br>DATA SOURCE: A comprehensive search from inception to 30 February 2019 was conducted in four databases (Medline/PubMed, Embase, Scopus, ClinicalTrials.gov).<br><br>ELIGIBILITY CRITERIA: RCTs reporting the resolution of diarrhoea associated with RCDI without relapse for at least 60 days after the end of treatments as the primary outcome.<br><br>DATA EXTRACTION AND SYNTHESIS: We extracted author, year of publication, study design and binomial data that represented the resolution of diarrhoea or adverse events of monoclonal antibodies and FMT infusion. Random-effects models were used for resolution rate of RCDI and adverse events. The Cochrane Risk of Bias tool was used to assess the quality of included RCTs.<br><br>RESULTS: Out of 1003 articles identified, seven RCTs involving 3043 patients contributed to the review. No difference was reported between single or multiple infusions of FMT and bezlotoxumab in resolving RCDI, (OR 1.53, 95% credible interval (CrI) 0.39 to 5.16) and (OR 2.86, 95% CrI 1.29 to 6.57), respectively. Patients treated with SAT alone or bezlotoxumab with SAT showed significantly lower rates of diarrhoea than FMT (OR 0, 95% CrI 0 to 0.09) and (OR 0, 95% CrI 0 to 0.19), respectively. There was no difference in terms of other adverse events.<br><br>CONCLUSIONS: This is the first network meta-analysis that has compared the recently Food and Drug Administration-approved monoclonal antibody bezlotoxumab with FMT for resolving RCDI. The quality of the included RCTs was variable. The findings of this study suggested no difference between single or multiple infusions of FMT and bezlotoxumab. However, FMT was associated with a higher rate of non-serious diarrhoea as opposed to SAT used alone or in combination with bezlotoxumab.}, }
@article {pmid31698603, year = {2019}, author = {Kang, XX and Yan, J and Huang, F and Yang, L}, title = {On the mechanism of antibiotic resistance and fecal microbiota transplantation.}, journal = {Mathematical biosciences and engineering : MBE}, volume = {16}, number = {6}, pages = {7057-7084}, doi = {10.3934/mbe.2019354}, pmid = {31698603}, issn = {1551-0018}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacterial Infections/*therapy ; Computer Simulation ; *Drug Resistance, Bacterial ; *Drug Resistance, Microbial ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Intestines/drug effects/microbiology ; Methicillin-Resistant Staphylococcus aureus ; Models, Theoretical ; Probiotics ; Risk ; }, abstract = {Antibiotic resistance is a growing threat to human health and is caused by mainly the overuse of antibiotics in clinical medicine. Clinically, drug resistance emerges after a series of antibiotic treatments, implying that each treatment changes the intestinal flora composition and the accumulations of these changes induce the resistance. But mathematically, this cumulative effect cannot be achieved by a general population model, because the system will return to its pre-treatment state (an isolated steady state) after each cure. Based on the fact that sensitive bacteria and resistant bacteria are similar in most respects except their reactions to antibiotics, we developed a mathematical model with a specific phase-space structure: instead of isolated points, the steady states of this system compose one-dimensional manifolds (line segments). This structure explains the fundamental mechanism of antibiotic resistance: after antibiotic treatment, the system cannot return to the pretreatment healthy steady state but rather slightly moves along the manifold to a different steady state. Each use of antibiotics can change the ratio of resistant to susceptible pathogens in the host. The change the ratio can persist and accumulate, and finally promotes the emergence of antimicrobial resistance. We also assessed key factors (such as pathogen composition, the amount and composition of beneficial bacteria, medication duration and bactericidal rates of drugs) influencing the development of drug resistance. In addition, we clarified how fecal microbiota transplantation affects the treatment of antibiotic-resistant infections. The effect is essentially a transfer towards the healthy state in the phase space. Finally, based on the mechanisms revealed by the mathematical models, we suggested some strategies to delay or prevent the emergence of drug resistance. These findings not only provide a solid theoretical basis for the treatment of antimicrobial resistance, but also inspire clues to the phenomenon of drug resistance.}, }
@article {pmid31690638, year = {2020}, author = {Manca, C and Boubertakh, B and Leblanc, N and Deschênes, T and Lacroix, S and Martin, C and Houde, A and Veilleux, A and Flamand, N and Muccioli, GG and Raymond, F and Cani, PD and Di Marzo, V and Silvestri, C}, title = {Germ-free mice exhibit profound gut microbiota-dependent alterations of intestinal endocannabinoidome signaling.}, journal = {Journal of lipid research}, volume = {61}, number = {1}, pages = {70-85}, pmid = {31690638}, issn = {1539-7262}, support = {//CIHR/Canada ; }, mesh = {Animals ; Endocannabinoids/*metabolism ; *Gastrointestinal Microbiome ; Intestines/*chemistry/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; *Signal Transduction ; }, abstract = {The gut microbiota is a unique ecosystem of microorganisms interacting with the host through several biochemical mechanisms. The endocannabinoidome (eCBome), a complex signaling system including the endocannabinoid system, approximately 50 receptors and metabolic enzymes, and more than 20 lipid mediators with important physiopathologic functions, modulates gastrointestinal tract function and may mediate host cell-microbe communications there. Germ-free (GF) mice, which lack an intestinal microbiome and so differ drastically from conventionally raised (CR) mice, offer a unique opportunity to explore the eCBome in a microbe-free model and in the presence of a reintroduced functional gut microbiome through fecal microbiota transplant (FMT). We aimed to gain direct evidence for a link between the microbiome and eCBome systems by investigating eCBome alterations in the gut in GF mice before and after FMT. Basal eCBome gene expression and lipid profiles were measured in various segments of the intestine of GF and CR mice at juvenile and adult ages using targeted quantitative PCR transcriptomics and LC-MS/MS lipidomics. GF mice exhibited age-dependent modifications in intestinal eCBome gene expression and lipid mediator levels. FMT from CR donor mice to age-matched GF male mice reversed several of these alterations, particularly in the ileum and jejunum, after only 1 week, demonstrating that the gut microbiome directly impacts the host eCBome and providing a cause-effect relationship between the presence or absence of intestinal microbes and eCBome signaling. These results open the way to new studies investigating the mechanisms through which intestinal microorganisms exploit eCBome signaling to exert some of their physiopathologic functions.}, }
@article {pmid31690163, year = {2020}, author = {Uehara, S and Yoneda, N and Higuchi, Y and Yamazaki, H and Suemizu, H}, title = {Metabolism of desloratadine by chimeric TK-NOG mice transplanted with human hepatocytes.}, journal = {Xenobiotica; the fate of foreign compounds in biological systems}, volume = {50}, number = {6}, pages = {733-740}, doi = {10.1080/00498254.2019.1688892}, pmid = {31690163}, issn = {1366-5928}, mesh = {Administration, Oral ; Animals ; Chimera ; Glucuronides ; Haplorhini/metabolism ; Hepatocytes/metabolism ; Histamine H1 Antagonists, Non-Sedating/metabolism ; Humans ; Loratadine/*analogs &amp; derivatives/metabolism ; Mice ; Rats ; }, abstract = {1. Desloratadine is an antiallergic drug with species-dependent metabolic profiles in mice, rats, monkeys and humans. We investigated whether humanized-liver mice could reproduce the reported human-specific in vivo metabolic profile for desloratadine in terms of the formation of 3-hydroxydesloratadine and its O-glucuronide.2. Hepatocytes prepared from humans and humanized-liver mice both preferentially catalyzed the formation of 3-hydroxydesloratadine and its O-glucuronide in vitro.3. After a single oral administration of desloratadine, plasma levels of desloratadine and its metabolites (3-hydroxydesloratadine and its O-glucuronide) in humanized-liver mice were lower and higher, respectively, than those in control mice.4. The amounts of 3-hydroxydesloratadine and its O-glucuronide excreted in humanized-liver mouse feces and urine were higher than those of the control mice, whereas 5- and 6-hydroxydesloratadine formation were predominant in the feces and urine samples from control mice. A significant correlation (r = 0.68) for the dose percentage of urinary and fecal metabolites of desloratadine was only observed between the humanized-liver mice and the reported values for humans.5. These results indicated that urinary 3-hydroxydesloratadine O-glucuronide and fecal desloratadine, 3-hydroxydesloratadine and 5-hydroxydesloratadine were the major excretion pathways of desloratadine in humanized-liver mice, which is reasonably similar to that reported for humans.}, }
@article {pmid31690143, year = {2020}, author = {Kumar, V and Fischer, M}, title = {Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond.}, journal = {Expert opinion on biological therapy}, volume = {20}, number = {1}, pages = {73-81}, doi = {10.1080/14712598.2020.1689952}, pmid = {31690143}, issn = {1744-7682}, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Treatment Outcome ; }, abstract = {Introduction: Fecal microbiota transplantation (FMT) is a procedure involving transfer of stool from a healthy donor into the intestinal tract of a diseased recipient to restore intestinal microbial composition and functionality. FMT's tremendous success in recurrent and refractory Clostridioides difficile infection (CDI) catalyzed gut microbiota research and opened the door to microbiome-based therapy for various gastrointestinal and other disorders.Areas covered: We used PubMed search engine to identify significant publications in the field of CDI and FMT. Here we present an overview of the current literature on FMT's use for recurrent, non-severe, severe, and fulminant CDI and on promising future application.Expert opinion: FMT as the best tool for treatment of antibiotic-refractory CDI has gained immense popularity over the last decade. The future of gut microbiota-based therapy should include oral formulations that contain well-described ingredients in effective doses, clear mechanism of action, and excellent safety profile.}, }
@article {pmid31689519, year = {2019}, author = {Wu, M and Li, P and An, Y and Ren, J and Yan, D and Cui, J and Li, D and Li, M and Wang, M and Zhong, G}, title = {Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota.}, journal = {Pharmacological research}, volume = {150}, number = {}, pages = {104489}, doi = {10.1016/j.phrs.2019.104489}, pmid = {31689519}, issn = {1096-1186}, mesh = {Animals ; CD4-Positive T-Lymphocytes/drug effects/immunology ; CD8-Positive T-Lymphocytes/drug effects/immunology ; Colitis, Ulcerative/*drug therapy/immunology/microbiology/pathology ; Colon/drug effects/pathology ; Dextran Sulfate ; Gastrointestinal Microbiome/*drug effects ; Male ; Mice, Inbred BALB C ; NF-kappa B/immunology ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology ; Phloretin/pharmacology/*therapeutic use ; Spleen/cytology/drug effects/immunology ; }, abstract = {Phloretin, extracted from the pericarp and velamen of apples or pears, is a dihydrochalcone flavonoid with anti-bacterial and anti-inflammatory activities. It has been reported that phloretin has anti-inflammatory effects in ulcerative colitis (UC) mice. However, the role of the gut microbiota in the phloretin anti-UC process remains unclear. In this study, we observed that the anti-UC effect of phloretin was affected by co-housing, probably because of the transmissible nature of the gut micobiota. Through fecal micobiota transplantation (FMT), the effects of the gut microbiota on the anti-UC of phloretin were further confirmed. UC was induced in mice by administrating 3% dextran sulfate sodium (DSS) in drinking water for 7 days. Phloretin (60 mg/kg) was administered by gavage every day during the experiment. Fecal microbes (10[9] CFU/mL) from phloretin-treated UC mice were administered by gavage to non-phloretin-treated UC mice for 7 days. The results showed that FMT, like phloretin, ameliorated UC by improving disease symptoms and colon inflammation, balancing inflammatory cytokines, maintaining intestinal barrier integrity, restoring systemic immune function, inhibiting NF-κB and NLRP3 inflammasome activation and ameliorating the oxidant stress. Both FMT and phloretin treatment increased the levels of Bacteroidetes, Alistipes and Lactobacillus and decreased those of Firmicutes, Oscillibacter and Ruminiclostridium_6. Correlation analysis between gut microbes and micro-environmental factors revealed that Alistipes abundance was negatively correlated with DAI, pathological score, and TNF-α, IL-6 and IL-1β levels, and Alistipes was more abundant in phloretin or FMT treated UC mice. Oscillibacter abundance was significantly positively correlated with IL-6 and IL-1β levels and pathological score, and Oscillibacter was increased in UC mice. Furthermore, network analysis of the dominant genera revealed that Alistipes abundance was negatively related to Oscillibacter abundance. In conclusion, this study suggests that the anti-UC effects of phloretin are achieved through regulation of the gut microbiota and phloretin has the potential to be developed as a promising agent for the treatment of UC.}, }
@article {pmid31688252, year = {2019}, author = {Singh, H and Ross, L and Smith, H and Borody, TJ and Lemberg, DA}, title = {Oral fecal microbiota transplant for recurrent Clostridium difficile in pediatric autoimmune enteropathy.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {31}, number = {12}, pages = {1602-1603}, doi = {10.1097/MEG.0000000000001548}, pmid = {31688252}, issn = {1473-5687}, mesh = {Child, Preschool ; Clostridioides difficile/*isolation &amp; purification ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Humans ; Male ; *Microbiota ; Mouth Mucosa/*microbiology ; Polyendocrinopathies, Autoimmune/*therapy ; Recurrence ; }, }
@article {pmid31687767, year = {2020}, author = {Rogers, WS and Westblade, LF and Soave, R and Jenkins, SG and van Besien, K and Singh, HK and Walsh, TJ and Small, CB and Shore, T and Crawford, CV and Satlin, MJ}, title = {Impact of a Multiplexed Polymerase Chain Reaction Panel on Identifying Diarrheal Pathogens in Hematopoietic Cell Transplant Recipients.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {71}, number = {7}, pages = {1693-1700}, doi = {10.1093/cid/ciz1068}, pmid = {31687767}, issn = {1537-6591}, mesh = {Adult ; *Clostridioides difficile/genetics ; Diarrhea/diagnosis/epidemiology ; Feces ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Multiplex Polymerase Chain Reaction ; Transplant Recipients ; }, abstract = {BACKGROUND: Diarrhea is common and associated with substantial morbidity among hematopoietic cell transplant (HCT) recipients, but the etiology is often not identified. Multiplexed polymerase chain reaction (PCR) assays increase the detection of diarrheal pathogens, but the impact of this technology in this population has not been evaluated.<br><br>METHODS: Our center replaced stool cultures and other conventional microbiologic methods with the FilmArray Gastrointestinal Panel (GI PCR) in June 2016. We reviewed all adult patients who received an HCT from June 2014-May 2015 (pre-GI PCR, n = 163) and from June 2016-May 2017 (post-GI PCR, n = 182) and followed them for 1 year after transplantation. Clostridioides difficile infection was diagnosed by an independent PCR test in both cohorts.<br><br>RESULTS: The proportion of patients with &#x2265;1 identified infectious diarrheal pathogen increased from 25% to 37% after implementation of GI PCR (P = .01). Eight patients (5%) in the pre-GI PCR cohort tested positive for a pathogen other than C. difficile versus 49 patients (27%) in the post-GI PCR cohort (P < .001). The most common non-C. difficile diarrheal pathogens in the post-GI PCR cohort were enteropathogenic Escherichia coli (n = 14, 8%), norovirus (n = 14, 8%), and Yersinia enterocolitica (n = 7, 4%). The percentage of diarrheal episodes with an identified infectious etiology increased from 14% to 23% (P = .001). Median total costs of stool testing per patient did not increase (pre: $473; post: $425; P = .25).<br><br>CONCLUSIONS: Infectious etiologies of diarrhea were identified in a higher proportion of HCT recipients after replacing conventional stool testing with a multiplexed PCR assay, without an increase in testing costs.}, }
@article {pmid31683278, year = {2019}, author = {Ianiro, G and Murri, R and Sciumè, GD and Impagnatiello, M and Masucci, L and Ford, AC and Law, GR and Tilg, H and Sanguinetti, M and Cauda, R and Gasbarrini, A and Fantoni, M and Cammarota, G}, title = {Incidence of Bloodstream Infections, Length of Hospital Stay, and Survival in Patients With Recurrent Clostridioides difficile Infection Treated With Fecal Microbiota Transplantation or Antibiotics: A Prospective Cohort Study.}, journal = {Annals of internal medicine}, volume = {171}, number = {10}, pages = {695-702}, doi = {10.7326/M18-3635}, pmid = {31683278}, issn = {1539-3704}, mesh = {Aged ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*epidemiology ; Clostridioides difficile ; Clostridium Infections/mortality/*therapy ; Cohort Studies ; *Fecal Microbiota Transplantation ; Female ; Humans ; Incidence ; Italy/epidemiology ; *Length of Stay ; Male ; Matched-Pair Analysis ; Recurrence ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is a risk factor for bloodstream infection (BSI). Fecal microbiota transplantation (FMT) is more effective than antibiotics in treating recurrent CDI, but its efficacy in preventing CDI-related BSI is uncertain.<br><br>OBJECTIVE: To assess incidence of primary BSI in patients with recurrent CDI treated with FMT versus antibiotics.<br><br>DESIGN: Prospective cohort study. Patients treated with FMT and those treated with antibiotics were matched on propensity score.<br><br>SETTING: Single academic medical center.<br><br>PATIENTS: 290 inpatients with recurrent CDI (57 patients per treatment in matched cohort).<br><br>INTERVENTION: FMT or antibiotics.<br><br>MEASUREMENTS: The primary outcome was primary BSI within 90 days. Secondary outcomes were length of hospitalization and overall survival (OS) at 90 days.<br><br>RESULTS: Of the 290 patients, 109 were treated with FMT and 181 received antibiotics. Five patients in the FMT group and 40 in the antibiotic group developed BSI. Because of differences in the patients treated with FMT versus antibiotics in many baseline characteristics, including number of recurrences and CDI severity, comparative analyses were limited to the matched cohort. Risk for BSI was 23 percentage points (95% CI, 10 to 35 percentage points) lower in the FMT group; the FMT group also had 14 fewer days of hospitalization (CI, 9 to 20 fewer days) and a 32-percentage point increase in OS (CI, 16 to 47 percentage points) compared with the antibiotic group.<br><br>LIMITATION: Nonrandomized study with potential for unmeasured or residual confounding; limited generalizability of the propensity score-matched cohort.<br><br>CONCLUSION: In a propensity score-matched cohort, patients with recurrent CDI treated with FMT were less likely to develop primary BSI.<br><br>PRIMARY FUNDING SOURCE: None.}, }
@article {pmid31682032, year = {2020}, author = {Rosa, CP and Pereira, JA and Cristina de Melo Santos, N and Brancaglion, GA and Silva, EN and Tagliati, CA and Novaes, RD and Corsetti, PP and de Almeida, LA}, title = {Vancomycin-induced gut dysbiosis during Pseudomonas aeruginosa pulmonary infection in a mice model.}, journal = {Journal of leukocyte biology}, volume = {107}, number = {1}, pages = {95-104}, doi = {10.1002/JLB.4AB0919-432R}, pmid = {31682032}, issn = {1938-3673}, mesh = {Animals ; Anti-Bacterial Agents/toxicity ; Disease Models, Animal ; Dysbiosis/*etiology/pathology ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects/*immunology ; Intestines/drug effects/immunology/*microbiology ; Lung/drug effects/immunology/*microbiology ; Mice ; Mice, Inbred C57BL ; Pseudomonas Infections/drug therapy/immunology/*microbiology ; Pseudomonas aeruginosa/drug effects/*immunology ; Vancomycin/*toxicity ; }, abstract = {Pseudomonas aeruginosa is one of the most common opportunistic pathogens causing respiratory infections in hospitals. Vancomycin, the antimicrobial agent usually used to treat bacterial nosocomial infections, is associated with gut dysbiosis. As a lung-gut immunologic axis has been described, this study aimed to evaluate both the immunologic and histopathologic effects on the lungs and the large intestine resulting from vancomycin-induced gut dysbiosis in the P. aeruginosa pneumonia murine model. Metagenomic analysis demonstrated that vancomycin-induced gut dysbiosis resulted in higher Proteobacteria and lower Bacteroidetes populations in feces. Given that gut dysbiosis could augment the proinflammatory status of the intestines leading to a variety of acute inflammatory diseases, bone marrow-derived macrophages were stimulated with cecal content from dysbiotic mice showing a higher expression of proinflammatory cytokines and lower expression of IL-10. Dysbiotic mice showed higher levels of viable bacteria in the lungs and spleen when acutely infected with P. aeruginosa, with more lung and cecal damage and increased IL-10 expression in bronchoalveolar lavage. The susceptible and tissue damage phenotype was reversed when dysbiotic mice received fecal microbiota transplantation. In spite of higher recruitment of CD11b+ cells in the lungs, there was no higher CD80+ expression, DC+ cell amounts or proinflammatory cytokine expression. Taken together, our results indicate that the bacterial community found in vancomycin-induced dysbiosis dysregulates the gut inflammatory status, influencing the lung-gut immunologic axis to favor increased opportunistic infections, for example, by P. aeruginosa.}, }
@article {pmid31678099, year = {2019}, author = {Treacy, PJ and Mazoyer, C and Falagario, U and Iannelli, A}, title = {Sexual Activity After Bariatric Surgery: A Prospective Monocentric Study Using the PISQ-IR Questionnaire.}, journal = {The journal of sexual medicine}, volume = {16}, number = {12}, pages = {1930-1937}, doi = {10.1016/j.jsxm.2019.09.004}, pmid = {31678099}, issn = {1743-6109}, mesh = {Adult ; Bariatric Surgery ; Fecal Incontinence/etiology ; Female ; Humans ; Middle Aged ; Obesity, Morbid/*surgery ; Pelvic Floor Disorders/etiology ; Pelvic Organ Prolapse/complications ; Prospective Studies ; Quality of Life/*psychology ; Sexual Behavior/*psychology ; Sexual Dysfunction, Physiological/*psychology ; Surveys and Questionnaires ; Urinary Incontinence/etiology ; }, abstract = {INTRODUCTION: Obesity can lead to pelvic floor disorders, interfering with women's sexual life; Prolapse/Incontinence Sexual Questionnaire-International Urogynecology Association-Revised (PISQ-IR) is a new instrument to measure sexual life in women with pelvic floor disorders.<br><br>AIMS: To assess the utility of using PISQ-IR in morbidly obese women undergoing bariatric surgery and to show the improvement of bariatric surgery on sexuality.<br><br>METHODS: This prospective monocentric study included all women who underwent bariatric surgery from June 2016-May 2017. Sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) was performed by 1 surgeon, and data were collected by 1 researcher. Demographics, medical history, number of deliveries, and type of bariatric surgery (SG or RYGB) were collected at baseline. At the 1-year follow-up consultation, postoperative complications, percentage of total body weight loss (TWL) and percentage excess weight loss were assessed. Questionnaires were given at baseline and at 1-year follow-up.<br><br>MAIN OUTCOME MEASURES: Postoperative complications and total weight loss were measured at the 1-year follow-up. Sexual activity, using the PISQ-IR, and pelvic organ prolapse, urinary incontinence, and anal incontinence, using the urinary symptom profile and PFDI (Pelvic Floor Distress Inventory) 20, were compared before surgery and at 1-year follow-up.<br><br>RESULTS: 72 patients were included at baseline, 54 (75%) were considered for final analysis (30 RYGB and 24 SG), and 51 patients were considered for PISQ-IR. The mean preoperative body mass index was 41&#x2009;&#xb1;&#x2009;5.4 kg/m[2], and mean age was 43&#x2009;&#xb1;&#x2009;11.8 years. Both procedures induced an important weight loss (mean TWL of 33%) and had a similar percentage of TWL for each procedure: 31 (15-46) for SG vs 34 (9-51) for RYGB. 9 patients (17 [6%]) became sexually active 1 year after surgery. For the sexually inactive population after 1 year, there was no differences in the PISQ-IR in the follow-up. When body mass index loss was >13 kg/m[2], a higher percentage of the sexually active population improved their different scores, and there were significant results for both global quality of life and desire (P&#xa0;= .026 and .046). The other questionnaires showed a significant decrease in urinary incontinence symptoms (P < .001) associated with weight loss, whereas there was no difference in terms of pelvic organ prolapse or anal incontinence.<br><br>CONCLUSION: PISQ-IR is a useful instrument to measure sexual function regarding pelvic floor disorders. Bariatric surgery improves sexual activity in obese women 1 year after surgery. Treacy PJ, Mazoyer C, Falagario U, et&#xa0;al. Sexual Activity After Bariatric Surgery: A Prospective Monocentric Study Using the PISQ-IR Questionnaire. J Sex Med 2019;16:1930-1937.}, }
@article {pmid31678050, year = {2020}, author = {Wieczorska, K and Stolarek, M and Stec, R}, title = {The Role of the Gut Microbiome in Colorectal Cancer: Where Are We? Where Are We Going?.}, journal = {Clinical colorectal cancer}, volume = {19}, number = {1}, pages = {5-12}, doi = {10.1016/j.clcc.2019.07.006}, pmid = {31678050}, issn = {1938-0674}, mesh = {Animals ; Carcinogenesis/*immunology ; Colon/immunology/microbiology/pathology ; Colorectal Neoplasms/diagnosis/immunology/*microbiology/therapy ; Combined Modality Therapy/methods ; Disease Models, Animal ; Disease Progression ; Dysbiosis/diagnosis/diet therapy/*immunology/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*immunology ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy/*methods ; Inflammation/immunology/microbiology/pathology ; Intestinal Mucosa/immunology/microbiology/pathology ; Probiotics/administration &amp; dosage ; Prognosis ; Rectum/immunology/microbiology/pathology ; Treatment Outcome ; }, abstract = {Microbiome (microbiota) is a community of all microorganisms inhabiting a specific site of the body, including pathogens, which distinguishes it from the physiological microflora. Intestinal dysbiosis plays a key role in the development of colorectal cancer. In the process of carcinogenesis, inflammation, immune response, and toxic metabolites play a significant role. Specific species of bacteria might affect the risk of colorectal cancer and growth of tumor already present. Assessment of changes in the intestinal microbiome during the development and progression of colorectal cancer might create a simple diagnostic tool, a useful biomarker, or might influence treatment strategies in colorectal cancer patients. Analysis of the gut microbiome provides the potential to develop noninvasive diagnostic tests that would be useful as new protective markers of colorectal cancer, prognostic markers in already present colorectal cancer, and predictive markers of response to treatment, especially immunotherapy.}, }
@article {pmid31676058, year = {2019}, author = {Kuhnen, A}, title = {Genetic and Environmental Considerations for Inflammatory Bowel Disease.}, journal = {The Surgical clinics of North America}, volume = {99}, number = {6}, pages = {1197-1207}, doi = {10.1016/j.suc.2019.08.014}, pmid = {31676058}, issn = {1558-3171}, mesh = {Environment ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Inflammatory Bowel Diseases/diagnosis/*genetics/*surgery ; Male ; Postoperative Complications/physiopathology/therapy ; Pouchitis/microbiology/*therapy ; Proctocolectomy, Restorative/adverse effects/*methods ; Prognosis ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract driven by an exaggerated immune response to luminal microbiota in susceptible individuals. It presents with a heterogenous pattern of clinical disease severity, location, and behavior. Understanding the interaction between the host genome, gut microbiome, and further environmental exposures in the development of IBD is in the early stages, and factors that trigger onset of disease in susceptible individuals remain unknown. This article addresses the genetic, microbial, and environmental influences on development of inflammatory bowel disease and the ability to manipulate these factors through surgery and medical therapy.}, }
@article {pmid31672964, year = {2019}, author = {Huang, F and Zheng, X and Ma, X and Jiang, R and Zhou, W and Zhou, S and Zhang, Y and Lei, S and Wang, S and Kuang, J and Han, X and Wei, M and You, Y and Li, M and Li, Y and Liang, D and Liu, J and Chen, T and Yan, C and Wei, R and Rajani, C and Shen, C and Xie, G and Bian, Z and Li, H and Zhao, A and Jia, W}, title = {Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {4971}, pmid = {31672964}, issn = {2041-1723}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Amidohydrolases/metabolism ; Animals ; Bile Acids and Salts/*metabolism ; Catechin/*analogs &amp; derivatives/pharmacology ; Chenodeoxycholic Acid/metabolism ; Cholesterol/metabolism ; Diet, High-Fat ; Fecal Microbiota Transplantation ; *Fermented Foods ; Fibroblast Growth Factors/drug effects/metabolism ; Gastrointestinal Microbiome/*drug effects/genetics/physiology ; Humans ; Hypercholesterolemia/*metabolism ; Ileum/drug effects/metabolism ; Lipogenesis/drug effects ; Liver/drug effects/metabolism ; Male ; Metabolomics ; Mice ; Plant Extracts/pharmacology ; RNA, Ribosomal, 16S ; Receptors, Cytoplasmic and Nuclear/drug effects/metabolism ; Signal Transduction ; *Tea ; Young Adult ; }, abstract = {Pu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant pigments in Pu-erh tea. Here, we show that theabrownin alters the gut microbiota in mice and humans, predominantly suppressing microbes associated with bile-salt hydrolase (BSH) activity. Theabrownin increases the levels of ileal conjugated bile acids (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepatic production and fecal excretion of BAs, reduced hepatic cholesterol, and decreased lipogenesis. The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene expression of enzymes in the alternative BA synthetic pathway, production of hepatic chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis. Our results shed light into the mechanisms behind the cholesterol- and lipid-lowering effects of Pu-erh tea, and suggest that decreased intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholesterolemia and anti-hyperlipidemia therapies.}, }
@article {pmid31668180, year = {2019}, author = {Pironi, L and Sasdelli, AS}, title = {Management of the Patient with Chronic Intestinal Pseudo-Obstruction and Intestinal Failure.}, journal = {Gastroenterology clinics of North America}, volume = {48}, number = {4}, pages = {513-524}, doi = {10.1016/j.gtc.2019.08.005}, pmid = {31668180}, issn = {1558-1942}, mesh = {Chronic Disease ; Fecal Microbiota Transplantation ; Gastrointestinal Agents/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Intestinal Pseudo-Obstruction/classification/*diagnosis/epidemiology/*therapy ; Intestines/transplantation ; Liver Transplantation ; Malabsorption Syndromes/etiology/*therapy ; Parenteral Nutrition, Home ; Trace Elements/administration &amp; dosage ; Vitamins/administration &amp; dosage ; }, abstract = {Chronic intestinal pseudo-obstruction (CIPO) is a severe form of intestinal dysmotility disorder, characterized by the impairment of gastrointestinal propulsion of the gut content in the absence of fixed occluding lesions. CIPO is a rare disease that can develop in both children and adults. CIPO is classified as primary/idiopathic, when no underlying disorder is demonstrated, or secondary, when related to systemic diseases. Diagnosis relies on the finding of chronic/recurrent obstructive type symptoms with radiological features of dilated intestine with air/fluid levels without any lumen occluding lesion. Therapy is based on nutrition, pharmacologic and surgical intervention and requires a multidisciplinary approach.}, }
@article {pmid31665947, year = {2019}, author = {Adams, JB and Borody, TJ and Kang, DW and Khoruts, A and Krajmalnik-Brown, R and Sadowsky, MJ}, title = {Microbiota transplant therapy and autism: lessons for the clinic.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {13}, number = {11}, pages = {1033-1037}, doi = {10.1080/17474124.2019.1687293}, pmid = {31665947}, issn = {1747-4132}, mesh = {Autism Spectrum Disorder/diagnosis/microbiology/psychology/*therapy ; Chronic Disease ; Constipation/diagnosis/microbiology/*therapy ; Diarrhea/diagnosis/microbiology/*therapy ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; Treatment Outcome ; }, abstract = {Introduction: The purpose of this review is to discuss Microbiota Transplant Therapy (MTT), a type of intensive intestinal microbiota transplantation (IMT), for people with autism spectrum disorders (ASD) and chronic gastrointestinal disorders (constipation and/or diarrhea).Areas covered: This paper briefly reviews IMT, gastrointestinal symptoms and gastrointestinal bacteria in children with ASD, and results and lessons learned from intensive MTT for autism.Expert opinion: An open-label study and a two-year follow-up suggest that MTT is relatively safe and effective in significantly reducing gastrointestinal disorders and autism symptoms, changing the gut microbiome structure, and increasing gut microbial diversity. Further research with larger, randomized, double-blind, placebo-controlled studies is warranted.}, }
@article {pmid31665575, year = {2019}, author = {DeFilipp, Z and Bloom, PP and Torres Soto, M and Mansour, MK and Sater, MRA and Huntley, MH and Turbett, S and Chung, RT and Chen, YB and Hohmann, EL}, title = {Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant.}, journal = {The New England journal of medicine}, volume = {381}, number = {21}, pages = {2043-2050}, doi = {10.1056/NEJMoa1910437}, pmid = {31665575}, issn = {1533-4406}, mesh = {Aged ; Bacteremia/*etiology/microbiology ; Drug Resistance, Bacterial ; Dysbiosis/etiology/*therapy ; Escherichia coli/drug effects/*isolation &amp; purification/metabolism ; Fatal Outcome ; Fecal Microbiota Transplantation/*adverse effects ; Feces/*microbiology ; Hepatic Encephalopathy/complications/therapy ; Humans ; Male ; Myelodysplastic Syndromes/complications/therapy ; beta-Lactamases/metabolism ; }, abstract = {Fecal microbiota transplantation (FMT) is an emerging therapy for recurrent or refractory Clostridioides difficile infection and is being actively investigated for other conditions. We describe two patients in whom extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli bacteremia occurred after they had undergone FMT in two independent clinical trials; both cases were linked to the same stool donor by means of genomic sequencing. One of the patients died. Enhanced donor screening to limit the transmission of microorganisms that could lead to adverse infectious events and continued vigilance to define the benefits and risks of FMT across different patient populations are warranted.}, }
@article {pmid31665573, year = {2019}, author = {Blaser, MJ}, title = {Fecal Microbiota Transplantation for Dysbiosis - Predictable Risks.}, journal = {The New England journal of medicine}, volume = {381}, number = {21}, pages = {2064-2066}, doi = {10.1056/NEJMe1913807}, pmid = {31665573}, issn = {1533-4406}, mesh = {*Bacteremia ; Dysbiosis ; Escherichia coli ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid31665572, year = {2019}, author = {Kassam, Z and Dubois, N and Ramakrishna, B and Ling, K and Qazi, T and Smith, M and Kelly, CR and Fischer, M and Allegretti, JR and Budree, S and Panchal, P and Kelly, CP and Osman, M}, title = {Donor Screening for Fecal Microbiota Transplantation.}, journal = {The New England journal of medicine}, volume = {381}, number = {21}, pages = {2070-2072}, doi = {10.1056/NEJMc1913670}, pmid = {31665572}, issn = {1533-4406}, mesh = {*Donor Selection/methods/statistics &amp; numerical data ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Nose/microbiology ; Prospective Studies ; }, }
@article {pmid31663453, year = {2019}, author = {Baudry, N and Starck, J and Aussel, C and Lund, K and Aletti, M and Duranteau, J and Banzet, S and Lataillade, JJ and Vicaut, E and Peltzer, J}, title = {Effect of Preconditioned Mesenchymal Stromal Cells on Early Microvascular Disturbance in a Mouse Sepsis Model.}, journal = {Stem cells and development}, volume = {28}, number = {24}, pages = {1595-1606}, doi = {10.1089/scd.2019.0134}, pmid = {31663453}, issn = {1557-8534}, mesh = {Animals ; Cell Adhesion/genetics/physiology ; Culture Media, Conditioned/pharmacology ; Disease Models, Animal ; Endothelium/drug effects ; Erythrocytes/drug effects ; Humans ; Interferon-gamma/genetics ; Leukocytes/drug effects ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*cytology/drug effects ; Mice ; Microcirculation/genetics/physiology ; Microvessels/*cytology/metabolism ; Sepsis/pathology/*therapy ; }, abstract = {Septic patients often die in a context of multiple organ dysfunction syndrome (MODS), despite the macro-hemodynamic parameters being normalized and after the onset of antibiotic therapy. Microcirculation injury during sepsis affects capillary permeability and leukocyte-endothelium interactions and is thought to be instrumental in organ injury. Several studies have demonstrated a beneficial effect of mesenchymal stromal cells (MSCs) injection on survival and organ dysfunctions in sepsis models. In vivo activity of MSCs also appears to be very much dependent on the information provided before injection. Indeed preconditioning by interferon γ (IFNγ; MSC-IFNγ) increases immunosuppressive capacity of MSCs in vitro and in vivo. Therefore, the objective was to evaluate the effect of MSC naive or IFNγ preconditioned on leukocyte-endothelium interactions in a polymicrobial sepsis model by intraperitoneal feces injection. Six hours (H6) after this induction, we used intravital microscopy in mice cremaster muscle venules to study the flow behavior of leukocytes. Plasmas were harvested to evaluate inflammation level and endothelial activation. We showed that MSC-IFNγ have a beneficial effect on microcirculation, by increasing the flow of white blood cells (WBCs) and the percentage of venules containing flowing WBCs, by significantly reducing the adhesion of WBCs and by increasing the average red blood cell velocity (VRBC). In conclusion, our results suggest that intravenous injection of preconditioned MSC-IFNγ improves microvascular hemodynamics in early phases of sepsis.}, }
@article {pmid31663118, year = {2020}, author = {Wei, S and Peng, W and Mai, Y and Li, K and Wei, W and Hu, L and Zhu, S and Zhou, H and Jie, W and Wei, Z and Kang, C and Li, R and Liu, Z and Zhao, B and Cai, Z}, title = {Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment.}, journal = {Journal of cellular physiology}, volume = {235}, number = {5}, pages = {4843-4855}, doi = {10.1002/jcp.29362}, pmid = {31663118}, issn = {1097-4652}, mesh = {Aged ; Animals ; Bacterial Outer Membrane/metabolism/*transplantation ; *Behavior, Animal ; Brain/*metabolism/pathology ; Case-Control Studies ; *Cognition ; Cognitive Dysfunction/*metabolism/microbiology/pathology/psychology ; Cytokines/metabolism ; Disease Models, Animal ; Extracellular Vesicles/metabolism/*transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Glycogen Synthase Kinase 3 beta/metabolism ; Humans ; Male ; Memory ; Mice, Inbred C57BL ; Middle Aged ; Morris Water Maze Test ; Phosphorylation ; tau Proteins/*metabolism ; }, abstract = {Outer membrane vesicles (OMVs) are nanosized vesicles produced by the gut microbiota (GM). The GM is well-known to be involved in the pathological process of Alzheimer's disease (AD). However, the mechanism of OMVs is not clear. In the present study, we demonstrated the involvement of OMVs in the development of cognitive (learning and memory) dysfunction induced by blood-brain barrier (BBB) disruption. More important, further study showed that OMVs induced tau phosphorylation by activating glycogen synthase kinase 3β (GSK-3β) in the hippocampus. OMVs activated astrocytes and microglia, increased secretion of inflammatory cytokines (nuclear factor κB, interleukin-1β, and tumour necrosis factor-α) in the hippocampus. Therefore, OMVs increase the permeability of the BBB and promote the activation of astrocytes and microglia, inducing an inflammatory response and tau hyperphosphorylation by activating the GSK-3β pathway and finally leading to cognitive impairment.}, }
@article {pmid31662862, year = {2019}, author = {Rokkas, T and Gisbert, JP and Gasbarrini, A and Hold, GL and Tilg, H and Malfertheiner, P and Megraud, F and O'Morain, C}, title = {A network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in recurrent Clostridium difficile infection.}, journal = {United European gastroenterology journal}, volume = {7}, number = {8}, pages = {1051-1063}, pmid = {31662862}, issn = {2050-6406}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*drug effects ; Clostridium Infections/epidemiology/*microbiology/*therapy ; Combined Modality Therapy/methods ; Fecal Microbiota Transplantation/*methods ; Female ; Fidaxomicin/therapeutic use ; Humans ; Middle Aged ; Placebos/administration &amp; dosage ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Recurrence remains a challenge in Clostridium difficile infection (CDI), and in this field fecal microbiota transplantation (FMT) has attracted significant interest. Network meta-analysis (NWM) has been established as an evidence-synthesis tool that incorporates direct and indirect evidence in a collection of randomized controlled trials. So far no NWM exists concerning therapeutic interventions for recurrent CDI (rCDI).<br><br>OBJECTIVE: In this NWM we assessed the comparative effectiveness of various therapies for rCDI to examine the efficacy rank order and determine the optimum therapeutic approach.<br><br>METHODS: A Bayesian network meta-analysis was performed to investigate the efficacy rank order of rCDI interventions.<br><br>RESULTS: Six eligible RCTs were entered into an NWM. They included 348 rCDI patients, in whom seven therapeutic interventions were used, i.e. donor fecal microbiota transplantation (DFMT), vancomycin, fidaxomicin, vancomycin&#x2009;+&#x2009;DFMT, vancomycin&#x2009;+&#x2009;bowel lavage, autologous FMT and placebo. DFMT showed the highest efficacy in comparison with vancomycin [odds ratio (95% credible interval), 20.02 (7.05-70.03)] and fidaxomicin (22.01 (4.38-109.63)).<br><br>CONCLUSION: This NWM showed that DFMT is the optimum therapeutic approach for rCDI, as it was the most efficacious among various therapeutic interventions, particularly in comparison with commonly used antibiotics such as vancomycin or fidaxomicin.}, }
@article {pmid31662860, year = {2019}, author = {Myneedu, K and Deoker, A and Schmulson, MJ and Bashashati, M}, title = {Fecal microbiota transplantation in irritable bowel syndrome: A systematic review and meta-analysis.}, journal = {United European gastroenterology journal}, volume = {7}, number = {8}, pages = {1033-1041}, pmid = {31662860}, issn = {2050-6406}, mesh = {Adult ; Colonoscopy/methods ; Duodenoscopy/methods ; Dysbiosis/diagnosis ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Gastroscopy/methods ; Humans ; Irritable Bowel Syndrome/pathology/psychology/*therapy ; Male ; Middle Aged ; Placebos/administration &amp; dosage ; Quality of Life ; Randomized Controlled Trials as Topic ; Severity of Illness Index ; }, abstract = {BACKGROUND: Modulating gut microbiota is a potential treatment for irritable bowel syndrome (IBS). This meta-analysis explored whether fecal microbiota transplantation (FMT) is successful in treating IBS.<br><br>METHODS: A systematic review was performed to find trials on FMT in IBS. Ratios and relative ratios (RR) of improvement for single-arm trials (SATs) and randomized controlled trials (RCTs) were calculated, respectively. Changes in IBS Severity Scoring System (IBS-SSS) and IBS Quality of Life (IBS-QOL) instrument compared to baseline in FMT versus placebo groups were pooled.<br><br>RESULTS: In SATs, 59.5% (95% confidence interval (CI) 49.1-69.3) of IBS patients showed significant improvement. In RCTs, there were no differences between FMT and control in improvement (RR=0.93 (95% CI 0.50-1.75)) or changes in the IBS-SSS and IBS-QOL.<br><br>CONCLUSIONS: FMT was not effective in IBS. Variations in FMT methods and patient factors may contribute to the heterogeneous results of the trials.}, }
@article {pmid31662511, year = {2019}, author = {Valdivia-Gandur, I and Beltrán, V and Borie, E and Astudillo-Rozas, W and Aceituno-Antezana, O and Ferrer-Valdivia, N and Engelke, W}, title = {Sinus Floor Augmentation by Intraoral Endoscopic Approach for Biomaterial Study in a Rabbit Model.}, journal = {In vivo (Athens, Greece)}, volume = {33}, number = {6}, pages = {1843-1849}, pmid = {31662511}, issn = {1791-7549}, mesh = {Animals ; Biocompatible Materials/*administration &amp; dosage ; Bone Transplantation/methods ; Cone-Beam Computed Tomography/methods ; Endoscopy/methods ; Female ; Male ; Models, Animal ; Rabbits ; Sinus Floor Augmentation/*methods ; }, abstract = {AIM: To develop a new surgical model for sinus floor augmentation (SFA) in rabbit for experimental purposes.<br><br>MATERIALS AND METHODS: Eight adult rabbits were used, two for a surgical design using the anatomical dissection study, and the other six for an endoscopically assisted intraoral approach of SFA unilaterally, creating a subantral space where an allograft biomaterial was deposited. SFA was verified through cone-beam computerized tomography. Healing, weight, food, feces, and behavior were evaluated for 4 weeks post-operatively.<br><br>RESULTS: All animals survived. There was no bleeding or infection; inflammation was mild. No changes were observed in terms of feeding, weight, feces, or behavior. Tissue healing was normal.<br><br>CONCLUSION: This model is a refinement of the experimental technique and is a real option for SFA, without compromising animal morbidity because of its conservative design. The minimally invasive approach with endoscopic assistance reduces bias and improves surgical predictability.}, }
@article {pmid31660360, year = {2019}, author = {Hocquart, M and Pham, T and Kuete, E and Tomei, E and Lagier, JC and Raoult, D}, title = {Successful Fecal Microbiota Transplantation in a Patient Suffering From Irritable Bowel Syndrome and Recurrent Urinary Tract Infections.}, journal = {Open forum infectious diseases}, volume = {6}, number = {10}, pages = {ofz398}, pmid = {31660360}, issn = {2328-8957}, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder affecting 9%-23% of the population across the world. The relative efficacy of fecal microbiota transplantation (FMT) on IBS symptoms was demonstrated in a double-blind, randomized study.<br><br>METHODS: We describe the case of a 73-year-old woman suffering from IBS (abdominal pain, bloating, and abundant and disabling diarrhea, with 10-15 stools a day) and repetitive urinary tract infection (UTI; 5 episodes in 6 months, including 3 the last 2 months) for several years, generating an impaired quality of life. She received an FMT with 400 mL of fecal infusion from a healthy donor via a nasogastric tube after bowel lavage. Her digestive microbiota was analyzed using culturomic and metagenomic targeting 16S rRNA sequencing methods.<br><br>RESULTS: Eight months after transplantation, we observed a significant reduction in frequency and improvement in stool consistency (3-4 molded stools a day against 10-15 before the transplant) and no recurrence of urinary infection (as previously reported). Using culturomics, we found 12 bacteria present in the fecal infusion and post-transplant stool; these were absent pretransplant. Three of them (Intestinimonas massiliensis, Oscillibacter massiliensis, and Provencibacter massiliensis) were previously discovered and cultivated in our laboratory using culturomics. Using metagenomics, we also observed 12 bacteria, different from those observed during culture, that could have been transferred to the patient by FMT.<br><br>CONCLUSIONS: In this case report, IBS symptoms and UTI frequency decreased after FMT UTI. Further studies involving more patients would be relevant to confirm this work and develop bacteriotherapy.}, }
@article {pmid31660354, year = {2019}, author = {Woodworth, MH and Hayden, MK and Young, VB and Kwon, JH}, title = {Corrigendum: The Role of Fecal Microbiota Transplantation in Reducing Intestinal Colonization With Antibiotic-Resistant Organisms: The Current Landscape and Future Directions.}, journal = {Open forum infectious diseases}, volume = {6}, number = {10}, pages = {ofz391}, doi = {10.1093/ofid/ofz391}, pmid = {31660354}, issn = {2328-8957}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; U54 CK000481/CK/NCEZID CDC HHS/United States ; U54 CK000607/CK/NCEZID CDC HHS/United States ; }, abstract = {[This corrects the article DOI: 10.1093/ofid/ofz288.][This corrects the article DOI: 10.1093/ofid/ofz288.].}, }
@article {pmid31660343, year = {2019}, author = {Hourigan, SK and Ahn, M and Gibson, KM and Pérez-Losada, M and Felix, G and Weidner, M and Leibowitz, I and Niederhuber, JE and Sears, CL and Crandall, KA and Oliva-Hemker, M}, title = {Fecal Transplant in Children With Clostridioides difficile Gives Sustained Reduction in Antimicrobial Resistance and Potential Pathogen Burden.}, journal = {Open forum infectious diseases}, volume = {6}, number = {10}, pages = {ofz379}, pmid = {31660343}, issn = {2328-8957}, support = {KL2 TR001877/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) treats Clostridioides difficile infection (CDI). Little is known regarding the changes in antimicrobial resistance (AMR) genes and potential pathogen burden that occur in pediatric recipients of FMT. The aim of this study was to investigate changes in AMR genes, potential pathogens, species, and functional pathways with FMT in children.<br><br>METHODS: Nine children with recurrent CDI underwent FMT. Stool was collected from donor and recipient pre-FMT and longitudinally post-FMT for up to 24 weeks. Shotgun metagenomic sequencing was performed. Reads were analyzed using PathoScope 2.0.<br><br>RESULTS: All children had resolution of CDI. AMR genes decreased post-FMT (P < .001), with a sustained decrease in multidrug resistance genes (P < .001). Tetracycline resistance genes increased post-FMT (P < .001). Very low levels of potential pathogens were identified in donors and recipients, with an overall decrease post-FMT (P < .001). Prevotella sp. 109 expanded in all recipients post-FMT, and no recipients had any clinical infection. Alpha diversity was lower in recipients vs donors pre-FMT (P < .001), with an increase post-FMT (P &#x2264; .002) that was sustained. Beta diversity differed significantly in pre- vs post-FMT recipient samples (P < .001). Bacterial species Faecalibacterium prausnitzii and Bacteroides ovatus showed higher abundance in donors than recipients (P = .008 and P = .040, respectively), with expansion post-FMT. Biosynthetic pathways predominated in the donor and increased in the recipient post-FMT.<br><br>CONCLUSIONS: FMT for CDI in children decreases AMR genes and potential pathogens and changes microbiota composition and function. However, acquisition of certain AMR genes post-FMT combined with low levels of potential pathogens found in donors suggests that further study is warranted regarding screening donors using metagenomics sequencing before FMT.}, }
@article {pmid31657769, year = {2019}, author = {Kuijper, EJ and Allegretii, J and Hawkey, P and Sokol, H and Goldenberg, S and Ianiro, G and Gasbarrini, A and Kump, P and Costello, SP and Keller, J and Vehreschild, MJGT}, title = {A necessary discussion after transmission of multidrug-resistant organisms through faecal microbiota transplantations.}, journal = {The Lancet. Infectious diseases}, volume = {19}, number = {11}, pages = {1161-1162}, doi = {10.1016/S1473-3099(19)30545-6}, pmid = {31657769}, issn = {1474-4457}, mesh = {*Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation/*adverse effects/methods/standards ; Government Regulation ; Humans ; Immunocompromised Host ; Microbial Sensitivity Tests ; Patient Safety ; United States ; United States Food and Drug Administration ; }, }
@article {pmid31657333, year = {2019}, author = {Li, S and Xu, N and Hua, R and Niu, X and Lyu, C and Li, M and Li, J}, title = {[Fecal microbiota transplantation regulates the cholinergic anti-inflammatory pathway in cerebral cortex of septic rats through intestinal microbiota].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {31}, number = {9}, pages = {1102-1107}, doi = {10.3760/cma.j.issn.2095-4352.2019.09.009}, pmid = {31657333}, issn = {2095-4352}, mesh = {Animals ; Anti-Inflammatory Agents ; Cerebral Cortex ; Cholinergic Agents ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Male ; Rats ; Rats, Sprague-Dawley ; *Sepsis ; Tumor Necrosis Factor-alpha ; }, abstract = {OBJECTIVE: To investigate the effects of fecal microbiota transplantation on septic gut flora and the cortex cholinergic anti-inflammatory pathway in rats.<br><br>METHODS: Sixty clean grade male Sprague-Dawley (SD) rats were divided into normal saline (NS) control group, sepsis model group and fecal microbiota transplantation group by random number table, with 20 rats in each group. The rat model of sepsis was reproduced by injection of 10 mg/kg lipopolysaccharide (LPS) via tail vein, the rats in the NS control group was given the same amount of NS. The rats in the fecal microbiota transplantation group received nasogastric infusion of feces from healthy donor on the 1st day, 2 mL each time, for 3 times a day, the other two groups were given equal dose of NS by gavage. Fecal samples were collected on the 7th day after modeling, the levels of intestinal microbiota composition was determined using the 16SrDNA gene sequencing technology. The brain function was evaluated by electroencephalogram (EEG), and the proportion of each waveform in EEG was calculated. After sacrifice of rats, the brain tissues were harvested, the levels of protein expression of &#x3b1;7 nicotinic acetylcholine receptor (&#x3b1;7nAChR) were determined by Western Blot, and positive cells of Iba-1 in brain tissue were detected by immunohistochemistry method. The levels of interleukins (IL-6 and IL-1&#x3b2;) and tumor necrosis factor-&#x3b1; (TNF-&#x3b1;) were determined by enzyme-linked immunosorbent assay (ELISA).<br><br>RESULTS: Seven days after the reproduction of the model, all rats in the NS control group survived, while 10 rats and 8 rats died in the sepsis model group and fecal microbiota transplantation group, respectively, with mortality rates of 50% and 40% respectively. Finally, there were 20 rats in the NS control group, 10 in the sepsis model group and 12 in the fecal microbiota transplantation group. Compared with the NS control group, the diversity and composition of intestinal flora were changed, the incidence of abnormal EEG increased significantly, the expression of &#x3b1;7nAchR in the cortex decreased significantly, and the levels of Iba-1, TNF-&#x3b1;, IL-6 and IL-1&#x3b2; were significantly increased in the model group, suggested that the intestinal flora was dysbiosis, and severe inflammatory reaction occurred in the cerebral cortex, and brain function was impaired. Compared with the model group, the diversity of intestinal flora in the fecal microbiota transplantation group was significantly increased (species index: 510.24&#xb1;58.76 vs. 282.50&#xb1;47.42, Chao1 index: 852.75&#xb1;25.24 vs. 705.50&#xb1;46.50, both P < 0.05), the dysbiosis of intestinal flora at phylum, family, genus level induced by LPS were also significantly reversed, and with the improvement of intestinal flora, the incidence of abnormal EEG waveforms was lower in the fecal microbiota transplantation group compared with that in the model group [25.0% (3/12) vs. 80.0% (8/10), P < 0.05], and the expression of &#x3b1;7nAChR protein in the cerebral cortex was significantly increased (&#x3b1;7nAChR/&#x3b2;-actin: 1.56&#xb1;0.05 vs. 0.82&#xb1;0.07, P < 0.05), immunohistochemistry analysis showed that Iba-1 positive expression of microglia decreased significantly, and cerebral cortex TNF-&#x3b1;, IL-6, IL-1&#x3b2; levels were significantly decreased [TNF-&#x3b1; (ng/L): 6.28&#xb1;0.61 vs. 12.02&#xb1;0.54, IL-6 (ng/L): 28.26&#xb1;3.15 vs. 60.58&#xb1;4.62, IL-1&#x3b2; (ng/L): 33.63&#xb1;3.48 vs. 72.56&#xb1;2.25, all P < 0.05].<br><br>CONCLUSIONS: The results reveal that fecal microbiota transplantation has remarkably modulated the dysbiosis of intestinal microbiota and activated cholinergic anti-inflammatory pathway, and ameliorate the brain dysfunction in septic rats.}, }
@article {pmid31654298, year = {2019}, author = {Aira, A and Fehér, C and Rubio, E and Soriano, A}, title = {The Intestinal Microbiota as a Reservoir and a Therapeutic Target to Fight Multi-Drug-Resistant Bacteria: A Narrative Review of the Literature.}, journal = {Infectious diseases and therapy}, volume = {8}, number = {4}, pages = {469-482}, pmid = {31654298}, issn = {2193-8229}, abstract = {The appearance and dissemination of antibiotic-resistant bacteria, particularly in specific closed environments such as intensive care units of acute care hospitals, have become a major health concern. The intestinal microbiota has various functions including host protection from overgrowth or colonization by unwanted bacteria. The exposure to antibiotics significantly reduces the bacterial density of intestinal microbiota leaving an ecologic void that can be occupied by potentially pathogenic and/or resistant bacteria frequently present in hospital settings. Consequently, the intestinal microbiota of inpatients acts as a major reservoir and plays a critical role in perpetuating the spread of resistant bacteria. There are novel innovative methods to protect the host microbiota during antibiotic treatment, but they do not offer a solution for already established colonization by resistant microorganisms. Fecal microbiota transfer (FMT) is a promising intervention to achieve this goal; however, controlled trials report lower success rates than initial retrospective studies, especially in case of gram negatives. The aim of the present article is to highlight the importance of the intestinal microbiota in the global spread of multi-drug-resistant (MDR) microorganisms and to review the recent advances to protect the human microbiota from the action of antibiotics as well as a critical discussion about the evidence of decolonization of MDR microorganisms by FMT.}, }
@article {pmid31648984, year = {2019}, author = {Ma, Y and Chen, H}, title = {Faecal microbiota transplantation, a promising way to treat colorectal cancer.}, journal = {EBioMedicine}, volume = {49}, number = {}, pages = {13-14}, pmid = {31648984}, issn = {2352-3964}, mesh = {Colorectal Neoplasms/diagnosis/*therapy ; *Fecal Microbiota Transplantation/methods ; Humans ; Treatment Outcome ; }, }
@article {pmid31644957, year = {2019}, author = {Cammarota, G and Gallo, A and Bibbò, S}, title = {Fecal microbiota transplant for C. difficile infection: Just say yes.}, journal = {Anaerobe}, volume = {60}, number = {}, pages = {102109}, doi = {10.1016/j.anaerobe.2019.102109}, pmid = {31644957}, issn = {1095-8274}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*physiology ; Clostridium Infections/diagnosis/*microbiology/*therapy ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; Recurrence ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {The burden of Clostridium difficile associated diarrhea is a worrying clinical issue worldwide, mainly as regarding the high incidence of recurrences after standard antibiotic therapy and the risk for more severe clinical manifestations. For this reason, new and more effective therapies are needed for the treatment of recurrent episodes. Fecal microbiota transplantation seems to be a valid tool considering the mechanism of action and the growing number of studies that demonstrate its clinical efficacy.}, }
@article {pmid31639033, year = {2019}, author = {Dai, M and Liu, Y and Chen, W and Buch, H and Shan, Y and Chang, L and Bai, Y and Shen, C and Zhang, X and Huo, Y and Huang, D and Yang, Z and Hu, Z and He, X and Pan, J and Hu, L and Pan, X and Wu, X and Deng, B and Li, Z and Cui, B and Zhang, F}, title = {Rescue fecal microbiota transplantation for antibiotic-associated diarrhea in critically ill patients.}, journal = {Critical care (London, England)}, volume = {23}, number = {1}, pages = {324}, pmid = {31639033}, issn = {1466-609X}, support = {-//Intestine Initiative Foundation/International ; BE2018751//Primary Research &amp; Development Plan of Jiangsu Province/International ; -//Jiangsu Provincial Medical Innovation Team/International ; 81600417//National Natural Science Foundation of China/International ; 2015BAI13B07//China Clinical Research Center for Digestive Diseases/International ; }, mesh = {APACHE ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*adverse effects/therapeutic use ; Child ; Child, Preschool ; China ; Critical Illness/therapy ; Diarrhea/etiology/physiopathology/*therapy ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/*methods/trends ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Antibiotic-associated diarrhea (AAD) is a risk factor for exacerbating the outcome of critically ill patients. Dysbiosis induced by the exposure to antibiotics reveals the potential therapeutic role of fecal microbiota transplantation (FMT) in these patients. Herein, we aimed to evaluate the safety and potential benefit of rescue FMT for AAD in critically ill patients.<br><br>METHODS: A series of critically ill patients with AAD received rescue FMT from Chinese fmtBank, from September 2015 to February 2019. Adverse events (AEs) and rescue FMT success which focused on the improvement of abdominal symptoms and post-ICU survival rate during a minimum of 12&#x2009;weeks follow-up were assessed.<br><br>RESULTS: Twenty critically ill patients with AAD underwent rescue FMT, and 18 of them were included for analysis. The mean of Acute Physiology and Chronic Health Evaluation (APACHE) II scores at intensive care unit (ICU) admission was 21.7&#x2009;&#xb1;&#x2009;8.3 (range 11-37). Thirteen patients received FMT through nasojejunal tube, four through gastroscopy, and one through enema. Patients were treated with four (4.2&#x2009;&#xb1;&#x2009;2.1, range 2-9) types of antibiotics before and during the onset of AAD. 38.9% (7/18) of patients had FMT-related AEs during follow-up, including increased diarrhea frequency, abdominal pain, increased serum amylase, and fever. Eight deaths unrelated to FMT occurred during follow-up. One hundred percent (2/2) of abdominal pain, 86.7% (13/15) of diarrhea, 69.2% (9/13) of abdominal distention, and 50% (1/2) of hematochezia were improved after FMT. 44.4% (8/18) of patients recovered from abdominal symptoms without recurrence and survived for a minimum of 12&#x2009;weeks after being discharged from ICU.<br><br>CONCLUSION: In this case series studying the use of FMT in critically ill patients with AAD, good clinical outcomes without infectious complications were observed. These findings could potentially encourage researchers to set up new clinical trials that will provide more insight into the potential benefit and safety of the procedure in the ICU.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT03895593 . Registered 29 March 2019 (retrospectively registered).}, }
@article {pmid31637019, year = {2019}, author = {Zhang, Z and Tang, H and Chen, P and Xie, H and Tao, Y}, title = {Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome.}, journal = {Signal transduction and targeted therapy}, volume = {4}, number = {}, pages = {41}, pmid = {31637019}, issn = {2059-3635}, abstract = {The trillions of microorganisms in the gut microbiome have attracted much attention recently owing to their sophisticated and widespread impacts on numerous aspects of host pathophysiology. Remarkable progress in large-scale sequencing and mass spectrometry has increased our understanding of the influence of the microbiome and/or its metabolites on the onset and progression of extraintestinal cancers and the efficacy of cancer immunotherapy. Given the plasticity in microbial composition and function, microbial-based therapeutic interventions, including dietary modulation, prebiotics, and probiotics, as well as fecal microbial transplantation, potentially permit the development of novel strategies for cancer therapy to improve clinical outcomes. Herein, we summarize the latest evidence on the involvement of the gut microbiome in host immunity and metabolism, the effects of the microbiome on extraintestinal cancers and the immune response, and strategies to modulate the gut microbiome, and we discuss ongoing studies and future areas of research that deserve focused research efforts.}, }
@article {pmid31634731, year = {2019}, author = {Gori, S and Inno, A and Belluomini, L and Bocus, P and Bisoffi, Z and Russo, A and Arcaro, G}, title = {Gut microbiota and cancer: How gut microbiota modulates activity, efficacy and toxicity of antitumoral therapy.}, journal = {Critical reviews in oncology/hematology}, volume = {143}, number = {}, pages = {139-147}, doi = {10.1016/j.critrevonc.2019.09.003}, pmid = {31634731}, issn = {1879-0461}, mesh = {Animals ; Antineoplastic Agents/adverse effects/pharmacology/*therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy/methods ; Neoplasms/*drug therapy/*microbiology ; }, abstract = {Gut microbiota is involved in gastrointestinal carcinogenesis. Also, it modulates the activity, efficacy and toxicity of several chemotherapy agents, such as gemcitabine, cyclophosphamide, irinotecan, cisplatin and 5-Fluorouracil, and target therapy, such as tyrosine kinase inhibitors. More recently, accumulating data suggest that the composition of gut microbiota may also affect efficacy and toxicity of cancer immunotherapy. Therefore, the manipulation of gut microbiota through antibiotics, probiotics, prebiotics or fecal transplantation has been investigating with the aim to improve efficacy and mitigate toxicity of anticancer drugs.}, }
@article {pmid31634104, year = {2020}, author = {Rogers, A and ElKadri, A}, title = {Clinical Guideline Highlights for the Hospitalist: Clostridium difficile Infections in Children.}, journal = {Journal of hospital medicine}, volume = {15}, number = {2}, pages = {98-100}, doi = {10.12788/jhm.3312}, pmid = {31634104}, issn = {1553-5606}, mesh = {Adolescent ; Child ; Child, Preschool ; Clostridioides difficile/isolation &amp; purification ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation ; *Hospitalists ; Humans ; Infant ; Infant, Newborn ; Practice Guidelines as Topic/*standards ; }, abstract = {GUIDELINE TITLE: Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA).<br><br>RELEASE DATE: February 15, 2018 PRIOR VERSIONS: Cohen SH, Gerding DN, Johnson S, et al; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010; 31:431-55.Gerding DN, Johnson S, Peterson LR, et al. Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol 1995;16:459-477.<br><br>DEVELOPER: IDSA and SHEA.<br><br>FUNDING SOURCE: Support for this guideline was provided by the IDSA and SHEA.<br><br>TARGET POPULATION: Children and adults with Clostridium difficile infections.}, }
@article {pmid31633563, year = {2020}, author = {Vink, JP and Otter, JA and Edgeworth, JD}, title = {Carbapenemase-producing Enterobacteriaceae - once positive always positive?.}, journal = {Current opinion in gastroenterology}, volume = {36}, number = {1}, pages = {9-16}, doi = {10.1097/MOG.0000000000000596}, pmid = {31633563}, issn = {1531-7056}, mesh = {Carbapenem-Resistant Enterobacteriaceae/*isolation &amp; purification ; Cost of Illness ; Drug Resistance, Multiple, Bacterial ; *Enterobacteriaceae Infections/diagnosis/epidemiology/etiology/therapy ; *Gastrointestinal Microbiome ; Humans ; Remission, Spontaneous ; Risk Factors ; Time Factors ; }, abstract = {PURPOSE OF REVIEW: This review provides an overview of gastrointestinal tract colonization with carbapenemase-producing Enterobacteriaceae (CPE), including risk factors for colonization, determinants for duration of colonization, and whether patients can decolonize, either spontaneously or via targeted interventions.<br><br>RECENT FINDINGS: CPE colonization is disseminating globally with increasing numbers of carbapenemases being identified in increasing patient cohorts. Numerous risk factors including repeated healthcare contact, patient co-morbidities and international travel have all been linked to increased rates of colonization. Duration of colonization has been investigated in various healthcare settings and ranges many months or even years. Although new methods for expediting decolonization are being investigated, including faecal microbiota transplantation, high quality evidence of impact is lacking.<br><br>SUMMARY: Current evidence indicates that CPE colonization usually persists throughout the duration of most hospital admissions, although the majority of patients will subsequently spontaneously decolonize. Difficulties remain in determining the point at which patients can be considered decolonized because of the lack acceptable criteria for defining eradication. This has significance implications for infection prevention and control measures during the initial and subsequent hospital admissions. Strategies to reduce the healthcare burden of CPE colonization continue to rely predominantly on preventing acquisition, whereas decolonization efforts remain a focus of research.}, }
@article {pmid31628414, year = {2019}, author = {Houben, T and Penders, J and Oligschlaeger, Y and Dos Reis, IAM and Bonder, MJ and Koonen, DP and Fu, J and Hofker, MH and Shiri-Sverdlov, R}, title = {Hematopoietic Npc1 mutation shifts gut microbiota composition in Ldlr[-/-] mice on a high-fat, high-cholesterol diet.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {14956}, pmid = {31628414}, issn = {2045-2322}, mesh = {Animals ; Bone Marrow Transplantation ; Cholesterol, Dietary ; Diet, High-Fat ; Female ; *Gastrointestinal Microbiome ; Granuloma/metabolism ; Hematopoietic Stem Cells/*cytology ; Hepatocytes/metabolism ; Inflammation ; Intracellular Signaling Peptides and Proteins/*genetics ; Kupffer Cells ; Lipid Metabolism ; Liver/metabolism ; Lysosomes/metabolism ; Male ; Metabolic Syndrome/*microbiology ; Mice ; Mice, Knockout ; Mutation ; Niemann-Pick C1 Protein ; Phenotype ; Polymorphism, Single Nucleotide ; RNA, Ribosomal, 16S/metabolism ; Receptors, LDL/genetics ; }, abstract = {While the link between diet-induced changes in gut microbiota and lipid metabolism in metabolic syndrome (MetS) has been established, the contribution of host genetics is rather unexplored. As several findings suggested a role for the lysosomal lipid transporter Niemann-Pick type C1 (NPC1) in macrophages during MetS, we here explored whether a hematopoietic Npc1 mutation, induced via bone marrow transplantation, influences gut microbiota composition in low-density lipoprotein receptor knockout (Ldlr[-/-]) mice fed a high-fat, high-cholesterol (HFC) diet for 12 weeks. Ldlr[-/-] mice fed a HFC diet mimic a human plasma lipoprotein profile and show features of MetS, providing a model to explore the role of host genetics on gut microbiota under MetS conditions. Fecal samples were used to profile the microbial composition by 16 s ribosomal RNA gene sequencing. The hematopoietic Npc1 mutation shifted the gut microbiota composition and increased microbial richness and diversity. Variations in plasma lipid levels correlated with microbial diversity and richness as well as with several bacterial genera. This study suggests that host genetic influences on lipid metabolism affect the gut microbiome under MetS conditions. Future research investigating the role of host genetics on gut microbiota might therefore lead to identification of diagnostic and therapeutic targets for MetS.}, }
@article {pmid31628021, year = {2019}, author = {Lleal, M and Sarrabayrouse, G and Willamil, J and Santiago, A and Pozuelo, M and Manichanh, C}, title = {A single faecal microbiota transplantation modulates the microbiome and improves clinical manifestations in a rat model of colitis.}, journal = {EBioMedicine}, volume = {48}, number = {}, pages = {630-641}, pmid = {31628021}, issn = {2352-3964}, mesh = {Animals ; Biodiversity ; Biomarkers ; Biopsy ; Colitis/*etiology/pathology/*therapy ; Disease Models, Animal ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/etiology/pathology/therapy ; Intestinal Mucosa/metabolism/microbiology/pathology ; Male ; Mice ; *Microbial Interactions ; Rats ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a novel potential therapy for inflammatory bowel diseases, but it is poorly characterised.<br><br>METHODS: We evaluated the performance of the mouse and rat as a pre-clinical model for human microbiota engraftment. We then characterised the effect of a single human stool transfer (HST) on a humanised model of DSS-induced colitis. Colonic and faecal microbial communities were analysed using the 16S rRNA approach and clinical manifestations were assessed in a longitudinal setting.<br><br>FINDINGS: The microbial community of rats showed greater similarity to that of humans, while the microbiome of mice showed less similarity to that of humans. Moreover, rats captured more human microbial species than mice after a single HST. Using the rat model, we showed that HST compensated faecal dysbiosis by restoring alpha-diversity and by increasing the relative abundance of health-related microbial genera. To some extent, HST also modulated the microbial composition of colonic tissue. These faecal and colonic microbial communities alterations led to a relative restoration of colon length, and a significant decrease in both epithelium damage and disease severity. Remarkably, stopping inflammation by removing DSS before HST caused a faster and greater recovery of both microbiome and clinical manifestation features.<br><br>INTERPRETATION: Our results indicate that the rat outperforms the mouse as a model for human microbiota engraftment and show that the efficacy of HST can be enhanced when inflammation stimulation is withdrawn. Finally, our findings support a new therapeutic strategy based on the use FMT combined with anti-inflammatory drugs.}, }
@article {pmid31627163, year = {2019}, author = {Lützhøft, DO and Sánchez-Alcoholado, L and Tougaard, P and Junker Mentzel, CM and Kot, W and Nielsen, DS and Hansen, AK}, title = {Short communication: Gut microbial colonization of the mouse colon using faecal transfer was equally effective when comparing rectal inoculation and oral inoculation based on 16S rRNA sequencing.}, journal = {Research in veterinary science}, volume = {126}, number = {}, pages = {227-232}, doi = {10.1016/j.rvsc.2019.09.009}, pmid = {31627163}, issn = {1532-2661}, mesh = {*Administration, Oral ; Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Colon/microbiology ; Fecal Microbiota Transplantation/methods/*veterinary ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Male ; Mice/microbiology/*surgery ; Mice, Inbred C57BL ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/analysis ; Random Allocation ; Specific Pathogen-Free Organisms/drug effects ; }, abstract = {In the present study we hypothesized that a higher degree of gut microbiota (GM) transfer and colonization could be reached by rectal inoculation compared to oral inoculation, which is commonly used in mouse studies for GM transfer. We treated C57BL/6NTac Specific Pathogen Free (SPF) mice with antibiotics and subsequently we inoculated these with GM from donor mice of the same strain by either the oral or the rectal inoculation method. 16S rRNA gene sequencing of the colon microbiota showed no difference in microbial community on account of inoculation method as determined by unweighted UniFrac distance metrics in C57BL/6NTac SPF mice. In addition, qPCR analysis on colon tissue revealed no difference in mRNA expression between the inoculation methods. Next, the SPF mice were compared to germ-free (GF)-mice to identify differences in inoculation efficacy. Whether the mice were antibiotic treated SPF or GF clearly influenced GM determined by 16S rRNA gene sequencing where the SPF mice experienced up-regulation of S24-7 (p = .0001) and a decrease in Rikenellaceae (p = .016) compared to GF mice. qPCR analysis on colon tissue revealed up-regulation in mRNA gene expression of Il6, Il10, Reg3g and transcription factor RORγt (Rorc) in GF mice compared to SPF mice on a significant level (p < .05). This gene expression profile is consistent with post colonization development of the intestinal barrier in GF mice.}, }
@article {pmid31624757, year = {2019}, author = {Xie, WR and Yang, XY and Xia, HH and Wu, LH and He, XX}, title = {Hair regrowth following fecal microbiota transplantation in an elderly patient with alopecia areata: A case report and review of the literature.}, journal = {World journal of clinical cases}, volume = {7}, number = {19}, pages = {3074-3081}, pmid = {31624757}, issn = {2307-8960}, abstract = {BACKGROUND: Alopecia areata is a hair loss disease associated with genetics, autoimmunity, and other factors. There is an intriguing link between alopecia areata and gut dysbiosis. Fecal microbiota transplantation (FMT) has been recommended to treat Clostridium difficile (previously known as Clostridioides difficile) infection, and has also shown potentials in the treatment of inflammatory bowel disease, irritable bowel syndrome, and non-alcohol fatty liver disease.<br><br>CASE SUMMARY: An 86-year-old man, with a history of sigmoid colon carcinoma, suffered from recurrent abdominal pain and distension, and diarrhea for six months, with inappetence. At admission, he was also diagnosed with depression. Upon physical examination, the patient presented with a 1.5 cm &#xd7; 2.0 cm alopecia areata on his right occiput. Due to the negative results of laboratory testing, capsule endoscopy, and colonoscopy, the patient was diagnosed with noninfectious diarrhea, depressive disorder, and patchy alopecia areata. Considering that noninfectious diarrhea in the elderly patient was mainly caused by gut dysbiosis, he was given six rounds of FMT. His diarrhea improved remarkably one month after FMT, with improved appetite and disappearance of abdominal pain, distension, and depressive symptoms. Surprisingly, he reported new hair growth on the affected region of his scalp, with some of his white hair gradually turning to black, without taking any other therapies for alopecia areata before and after FMT.<br><br>CONCLUSION: FMT might act as a potential therapy for patients who suffer from alopecia areata. Large and well-designed studies are required to confirm the role of FMT in alopecia areata.}, }
@article {pmid31624266, year = {2019}, author = {Annavajhala, MK and Gomez-Simmonds, A and Macesic, N and Sullivan, SB and Kress, A and Khan, SD and Giddins, MJ and Stump, S and Kim, GI and Narain, R and Verna, EC and Uhlemann, AC}, title = {Colonizing multidrug-resistant bacteria and the longitudinal evolution of the intestinal microbiome after liver transplantation.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {4715}, pmid = {31624266}, issn = {2041-1723}, support = {R01 AI116939/AI/NIAID NIH HHS/United States ; T32 AI100852/AI/NIAID NIH HHS/United States ; TL1 TR001875/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/*pharmacology ; Bacteria/classification/drug effects/genetics ; Drug Resistance, Multiple, Bacterial/*drug effects/genetics ; Dysbiosis/genetics/microbiology/prevention &amp; control ; End Stage Liver Disease/microbiology/*therapy ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Humans ; Liver Transplantation/*methods ; Male ; Middle Aged ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Infections by multidrug-resistant bacteria (MDRB) remain a leading cause of morbidity and mortality after liver transplantation (LT). Gut dysbiosis characteristic of end-stage liver disease may predispose patients to intestinal MDRB colonization and infection, in turn exacerbating dysbiosis. However, relationships between MDRB colonization and dysbiosis after LT remain unclear. We prospectively recruited 177 adult patients undergoing LT at a single tertiary care center. 16 S V3-V4 rRNA sequencing was performed on 723 fecal samples collected pre-LT and periodically until one-year post-LT to test whether MDRB colonization was associated with decreased microbiome diversity. In multivariate linear mixed-effect models, MDRB colonization predicts reduced Shannon α-diversity, after controlling for underlying liver disease, antibiotic exposures, and clinical complications. Importantly, pre-LT microbial markers predict subsequent colonization by MDRB. Our results suggest MDRB colonization as a major, previously unrecognized, marker of persistent dysbiosis. Therapeutic approaches accounting for microbial and clinical factors are needed to address post-transplant microbiome health.}, }
@article {pmid31623898, year = {2019}, author = {Heo, Y and Park, HS and Shin, CS and Yoo, KC and Kim, D and Lee, T}, title = {Successful Treatment of Life-Threatening Small Bowel Bleeding With Thalidomide After Living Donor Kidney Transplantation: A Case Report.}, journal = {Transplantation proceedings}, volume = {51}, number = {9}, pages = {3092-3098}, doi = {10.1016/j.transproceed.2019.07.009}, pmid = {31623898}, issn = {1873-2623}, mesh = {Aged ; Angiogenesis Inhibitors/*therapeutic use ; Gastrointestinal Hemorrhage/*drug therapy ; Humans ; Immunosuppressive Agents/adverse effects ; Kidney Transplantation/*adverse effects ; Living Donors ; Male ; Melena/immunology ; Middle Aged ; Postoperative Complications/*drug therapy/etiology ; Tacrolimus/adverse effects ; Thalidomide/*therapeutic use ; }, abstract = {Gastrointestinal bleeding after kidney transplantation is a complication that can occur from immunosuppressant use. We present a case of refractory small bowel bleeding treated successfully with thalidomide after multiple failed attempts of conventional treatment. A 65-year-old male patient with diabetic nephropathy underwent living donor kidney transplantation. The surgery was uneventful, however, he developed immunosuppressant-induced melena with unstable vital signs 11 days later. There were a total of 4 bleeding episodes until the 90th postoperative day, and he received a total of 290 units of red blood cell transfusion during this period. Endoscopic clipping, transarterial embolization, and 2 surgical interventions failed to stop the bleeding. A trial of thalidomide 100 mg per day finally stopped the bleeding and the patient was discharged on the 110th postoperative day with a functioning renal graft. This case shows that thalidomide can be a safe option to treat immunosuppressant-induced refractory gastrointestinal bleeding in the setting of kidney transplantation. Additionally, this is the first case that reports the survival of a renal graft after more than 3000 mL of transfusion.}, }
@article {pmid31623075, year = {2019}, author = {Barathikannan, K and Chelliah, R and Rubab, M and Daliri, EB and Elahi, F and Kim, DH and Agastian, P and Oh, SY and Oh, DH}, title = {Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation.}, journal = {Microorganisms}, volume = {7}, number = {10}, pages = {}, pmid = {31623075}, issn = {2076-2607}, support = {2018-2019//Kangwon National University/ ; P00004989//Korean Ministry of SMEs and start-ups (MSS), under the supervision of the Korea Institute for Advancement of Technology (KIAT), "Regional specialized industrial development program/ ; 2018007551//National Research Foundation of Korea (NRF)/ ; }, abstract = {The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed.}, }
@article {pmid31622696, year = {2020}, author = {Albillos, A and de Gottardi, A and Rescigno, M}, title = {The gut-liver axis in liver disease: Pathophysiological basis for therapy.}, journal = {Journal of hepatology}, volume = {72}, number = {3}, pages = {558-577}, doi = {10.1016/j.jhep.2019.10.003}, pmid = {31622696}, issn = {1600-0641}, mesh = {Animals ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/metabolism/microbiology ; Liver/metabolism ; Liver Cirrhosis/drug therapy/*metabolism/*microbiology ; Liver Diseases, Alcoholic/drug therapy/*metabolism/*microbiology ; Molecular Targeted Therapy/methods ; Non-alcoholic Fatty Liver Disease/drug therapy/*metabolism/*microbiology ; }, abstract = {The gut-liver axis refers to the bidirectional relationship between the gut and its microbiota, and the liver, resulting from the integration of signals generated by dietary, genetic and environmental factors. This reciprocal interaction is established by the portal vein which enables transport of gut-derived products directly to the liver, and the liver feedback route of bile and antibody secretion to the intestine. The intestinal mucosal and vascular barrier is the functional and anatomical structure that serves as a playground for the interactions between the gut and the liver, limiting the systemic dissemination of microbes and toxins while allowing nutrients to access the circulation and to reach the liver. The control of microbial communities is critical to maintaining homeostasis of the gut-liver axis, and as part of this bidirectional communication the liver shapes intestinal microbial communities. Alcohol disrupts the gut-liver axis at multiple interconnected levels, including the gut microbiome, mucus barrier, epithelial barrier and at the level of antimicrobial peptide production, which increases microbial exposure and the proinflammatory environment of the liver. Growing evidence indicates the pathogenetic role of microbe-derived metabolites, such as trimethylamine, secondary bile acids, short-chain fatty acids and ethanol, in the pathogenesis of non-alcoholic fatty liver disease. Cirrhosis by itself is associated with profound alterations in gut microbiota and damage at the different levels of defence of the intestinal barrier, including the epithelial, vascular and immune barriers. The relevance of the severe disturbance of the intestinal barrier in cirrhosis has been linked to translocation of live bacteria, bacterial infections and disease progression. The identification of the elements of the gut-liver axis primarily damaged in each chronic liver disease offers possibilities for intervention. Beyond antibiotics, upcoming therapies centred on the gut include new generations of probiotics, bacterial metabolites (postbiotics), faecal microbial transplantation, and carbon nanoparticles. FXR-agonists target both the gut and the liver and are currently being tested in different liver diseases. Finally, synthetic biotic medicines, phages that target specific bacteria or therapies that create physical barriers between the gut and the liver offer new therapeutic approaches.}, }
@article {pmid31622538, year = {2020}, author = {Zou, M and Jie, Z and Cui, B and Wang, H and Feng, Q and Zou, Y and Zhang, X and Yang, H and Wang, J and Zhang, F and Jia, H}, title = {Fecal microbiota transplantation results in bacterial strain displacement in patients with inflammatory bowel diseases.}, journal = {FEBS open bio}, volume = {10}, number = {1}, pages = {41-55}, pmid = {31622538}, issn = {2211-5463}, mesh = {Adult ; Bacteria/*metabolism ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Humans ; Inflammatory Bowel Diseases/metabolism/*microbiology ; Male ; Middle Aged ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT), which is thought to have the potential to correct dysbiosis of gut microbiota, has been used to treat inflammatory bowel disease (IBD) for almost a decade. Here, we report an interventional prospective cohort study performed to elucidate the extent of and processes underlying microbiota engraftment in IBD patients after FMT treatment. The cohort included two categories of patients: (a) patients with moderate to severe Crohn's disease (CD) (Harvey-Bradshaw Index ≥ 7, n = 11) and (b) patients with ulcerative colitis (UC) (Montreal classification S2 and S3, n = 4). All patients were treated with a single FMT (via mid-gut, from healthy donors), and follow-up visits were performed at baseline, 3 days, 1 week, and 1 month after FMT (missing time points included). At each follow-up time point, fecal samples and clinical metadata were collected. For comparative analysis, 10 fecal samples from 10 healthy donors were included to represent the diversity level of normal gut microbiota. Additionally, the metagenomic data of 25 fecal samples from five individuals with metabolic syndrome who underwent autologous FMT treatment were downloaded from a previous published paper to represent fluctuations in microbiota induced during FMT. All fecal samples underwent shotgun metagenomic sequencing. We found that 3 days after FMT, 11 out of 15 recipients were in remission (three out of four UC recipients; 8 out of 11 CD recipients). Generally, bacterial colonization was observed to be lower in CD recipients than in UC recipients at both species and strain levels. Furthermore, across species, different strains displayed disease-specific displacement advantages under two-disease status. Finally, most post-FMT species (> 80%) could be properly predicted (area under the curve > 85%) using a random forest classification model, with the gut microbiota composition and clinical parameters of pre-FMT recipients acting as factors that contribute to prediction accuracy.}, }
@article {pmid31620079, year = {2019}, author = {Mandrioli, J and Amedei, A and Cammarota, G and Niccolai, E and Zucchi, E and D'Amico, R and Ricci, F and Quaranta, G and Spanu, T and Masucci, L}, title = {FETR-ALS Study Protocol: A Randomized Clinical Trial of Fecal Microbiota Transplantation in Amyotrophic Lateral Sclerosis.}, journal = {Frontiers in neurology}, volume = {10}, number = {}, pages = {1021}, pmid = {31620079}, issn = {1664-2295}, abstract = {Background and Rationale: Among the key players in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), microglia and T regulatory lymphocytes (Treg) are candidate cells for modifying the course of the disease. The gut microbiota (GM) acts by shaping immune tolerance and regulating the Treg number and suppressive function, besides circulating neuropeptides, and other immune cells that play in concert through the gut-brain axis. Previous mouse models have shown an altered enteric flora in early stage ALS, pointing to a possible GM role in ALS pathogenesis. Fecal Microbial Transplantation (FMT) is a well-known therapeutic intervention used to re-establish the proper microenvironment and to modulate enteric and systemic immunity. Methods: We are going to perform a multicenter randomized double-blind clinical trial employing FMT as a therapeutic intervention for ALS patients (NCT0376632). Forty-two ALS patients, at an early stage, will be enrolled with a 2:1 allocation ratio (28 FMT-treated patients vs. 14 controls). Study duration will be 12 months per patient. Three endoscopic procedures for intestinal biopsies in FMT and control groups are predicted at baseline, month 6 and month 12; at baseline and at month 6 fresh feces from healthy donors will be infused at patients in the intervention arm. The primary outcome is a significant change in Treg number between FMT-treated patients and control arm from baseline to month 6. Secondary outcomes include specific biological aims, involving in-depth analysis of immune cells and inflammatory status changes, central and peripheral biomarkers of ALS, besides comprehensive analysis of the gut, saliva and fecal microbiota. Other secondary aims include validated clinical outcomes of ALS (survival, forced vital capacity, and modifications in ALSFRS-R), besides safety and quality of life. Expected Results: We await FMT to increase Treg number and suppressive functionality, switching the immune system surrounding motorneurons to an anti-inflammatory, neuroprotective status. Extensive analysis on immune cell populations, cytokines levels, and microbiota (gut, fecal and saliva) will shed light on early processes possibly leading the degenerative ALS course. Conclusions: This is the first trial with FMT as a potential intervention to modify immunological response to ALS and disease progression at an early stage.}, }
@article {pmid31617299, year = {2020}, author = {Spinner, JA and Bocchini, CE and Luna, RA and Thapa, S and Balderas, MA and Denfield, SW and Dreyer, WJ and Nagy-Szakal, D and Ihekweazu, FD and Versalovic, J and Savidge, T and Kellermayer, R}, title = {Fecal microbiota transplantation in a toddler after heart transplant was a safe and effective treatment for recurrent Clostridiodes difficile infection: A case report.}, journal = {Pediatric transplantation}, volume = {24}, number = {1}, pages = {e13598}, pmid = {31617299}, issn = {1399-3046}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; U01-AI24290/NH/NIH HHS/United States ; }, mesh = {Child, Preschool ; *Clostridioides difficile ; Clostridium Infections/etiology/immunology/*therapy ; *Fecal Microbiota Transplantation ; Female ; *Heart Transplantation ; Humans ; *Immunocompromised Host ; Postoperative Complications/immunology/*therapy ; Recurrence ; }, abstract = {Pediatric recipients of SOT have a significantly increased risk of Clostridiodes (formerly Clostridium) difficile infection (CDI), which is associated with adverse outcomes after SOT. Alterations to the intestinal microbiota community structure increase the risk of CDI. FMT is a safe and effective treatment for recurrent CDI in immunocompetent children and adults. While there are increasing data that FMT in immunosuppressed patients is safe and effective without increased risk of infection, data regarding safety and efficacy of FMT in children after SOT are limited. To our knowledge, we report the youngest immunocompromised patient to undergo FMT and the third overall case of FMT in a child after HTx. Our patient presented with five episodes of rCDI in 6 months, and 16S rRNA genetic analysis revealed significant loss of overall microbiota community structure and diversity prior to FMT compared with a donor and a healthy, age-matched control. After FMT, marked and prolonged (at least 16 months) shifts in the recipient microbiota community structure and diversity were evident, approaching that of donor and healthy, age-matched control. FMT was well tolerated, restored microbial diversity without any graft or transplant complications, and prevented further rCDI episodes after more than 4 years of follow-up.}, }
@article {pmid31617205, year = {2020}, author = {Sharma, A and Das, P and Buschmann, M and Gilbert, JA}, title = {The Future of Microbiome-Based Therapeutics in Clinical Applications.}, journal = {Clinical pharmacology and therapeutics}, volume = {107}, number = {1}, pages = {123-128}, doi = {10.1002/cpt.1677}, pmid = {31617205}, issn = {1532-6535}, mesh = {Animals ; Drug-Related Side Effects and Adverse Reactions/etiology/*prevention &amp; control ; Fecal Microbiota Transplantation/methods ; Humans ; Microbiota/*physiology ; Pharmaceutical Preparations/*metabolism ; Probiotics/administration &amp; dosage ; }, abstract = {The microbiome, a collection of microorganisms, their genomes, and the surrounding environmental conditions, is akin to a human organ, and knowledge is emerging on its role in human health and diseases. The influence of the microbiome in drug response has only been investigated in detail for the last 10 years. The human microbiome is a complex and highly dynamic system, which varies dramatically between individuals, yet there exists a common core microbiome that is heritable and can be transmitted to progeny. Here, we review the role of the human microbiome, which is now widely accepted as a major factor that drives the interpersonal variation in therapeutic response. We describe examples in which the microbiome modifies drug action. Despite its complexity, the microbiome can be readily altered, with the potential to increase the benefits and reduce the toxicity and side effects associated with pharmaceutical drugs. The potential of new microbiome-based strategies, such as fecal microbiota transplant, probiotics, and phage therapy, as promising medical therapeutics are outlined. We also suggest a combination reductionist and system-level approaches that could be applied to further investigate the role of microbiota in drug metabolism modulation of drug response. Finally, we emphasize the importance of combining microbiome and pharmacology studies as a novel means to treat disease and reduce side effects.}, }
@article {pmid31616437, year = {2019}, author = {Heimesaat, MM and Mrazek, K and Bereswill, S}, title = {Murine Fecal Microbiota Transplantation Alleviates Intestinal and Systemic Immune Responses in Campylobacter jejuni Infected Mice Harboring a Human Gut Microbiota.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2272}, pmid = {31616437}, issn = {1664-3224}, mesh = {Animals ; Campylobacter Infections/*immunology/microbiology ; Campylobacter jejuni/*immunology/physiology ; Cytokines/immunology/metabolism ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/genetics/*immunology ; Host-Pathogen Interactions/immunology ; Humans ; Immune System/*immunology/microbiology/pathology ; Inflammation/immunology/metabolism/microbiology ; Inflammation Mediators/immunology/metabolism ; Intestines/*immunology/microbiology/pathology ; Mice, Inbred C57BL ; }, abstract = {Human campylobacteriosis constitutes a zoonotic food-borne disease and a progressively rising health burden of significant socioeconomic impact. We have recently shown that conventional mice are protected from Campylobacter jejuni infection, which was not the case for human microbiota associated (hma) mice indicating that the host-specific gut microbiota composition primarily determines susceptibility to or resistance against C. jejuni infection. In our present preclinical intervention study we addressed whether gut microbiota changes in stably C. jejuni infected hma mice following murine fecal microbiota transplantation (mFMT) could alleviate pathogen-induced immune responses. To accomplish this, secondary abiotic C57BL/6 mice were generated by broad-spectrum antibiotic treatment, perorally reassociated with a complex human gut microbiota and challenged with C. jejuni by gavage. Seven days later C. jejuni infected hma mice were subjected to peroral mFMT on 3 consecutive days. Within a week post-mFMT fecal pathogenic burdens had decreased by two orders of magnitude, whereas distinct changes in the gut microbiota composition with elevated numbers of lactobacilli and bifidobacteria could be assessed. In addition, mFMT resulted in less C. jejuni induced apoptotic responses in colonic epithelia, reduced numbers of macrophages and monocytes as well as of T lymphocytes in the large intestinal mucosa and lamina propria and in less distinct intestinal pro-inflammatory cytokine secretion as compared to mock challenge. Strikingly, inflammation dampening effects of mFMT were not restricted to the intestinal tract, but could also be observed systemically as indicated by elevated serum concentrations of pro-inflammatory cytokines such as TNF-α, IL-12p70, and IL-6 in C. jejuni infected hma mice of the mock, but not the mFMT cohort. In conclusion, our preclinical mFMT intervention study provides evidence that changes in the gut microbiota composition which might be achieved by pre- or probiotic formulations may effectively lower intestinal C. jejuni loads, dampen both, pathogen-induced intestinal and systemic inflammatory sequelae and may represent a useful tool to treat continuous shedding of C. jejuni by asymptomatic carriers which is critical in the context of food production, hospitalization and immunosuppression.}, }
@article {pmid31613980, year = {2019}, author = {Ersöz Alan, B and Gülerman, F}, title = {[The Role of Gut Microbiota in Autism Spectrum Disorder].}, journal = {Turk psikiyatri dergisi = Turkish journal of psychiatry}, volume = {30}, number = {3}, pages = {210-219}, pmid = {31613980}, issn = {2651-3463}, mesh = {Autism Spectrum Disorder/*psychology ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Human microbiota are colonies of microorganisms located in different parts of the human body with diverse functions. Healthy gut microbiota comprises differing ratios of microoganisms wholly contributing to metabolic and other molecular reactions in a healthy, functioning body. After the demonstration of the bidirectional interaction between the central nervous system and gut microbiota through neuroendocrine, neuroimmune, and autonomic nervous mechanisms, investigations have been started on the microbiota-gut-brain axis in psychiatric disorders. Autism spectrum disorder (ASD), which is a neurodevelopmental disorder of early childhood, is one of these disorders. Most of such studies were cross-sectional and mainly investigated the bacterial species. Changes in gut microbiota composition and the leaky gut syndrome are some of the hypotheses proposed to explain the core symptoms and gastrointestinal (GI) symptoms of ASD. Probiotics, prebiotics, fecal microbiota transplantation, diet have been proposed as treatment options. However, the role of microbiota in diagnosis, followup, and treatment is not yet clear. The bidirectional interaction between central nervous system and intestinal microbiota makes it difficult to establish the cause-effect relationship. The current data on microbiota may be useful to plan patient-specific treatment in autistic children with GI symptoms. This article aims to review the results of the studies on microbiota in animal models and children and discuss the emerging clinical relationship of ASD and gut microbiota.}, }
@article {pmid31612528, year = {2019}, author = {Tixier, EN and Verheyen, E and Ungaro, RC and Grinspan, AM}, title = {Faecal microbiota transplant decreases mortality in severe and fulminant Clostridioides difficile infection in critically ill patients.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {50}, number = {10}, pages = {1094-1099}, pmid = {31612528}, issn = {1365-2036}, support = {K23 DK111995/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/pathogenicity ; Clostridium Infections/epidemiology/*mortality/*therapy ; Cohort Studies ; Critical Illness/*mortality/*therapy ; *Fecal Microbiota Transplantation/mortality/statistics &amp; numerical data ; Female ; Humans ; Intensive Care Units/statistics &amp; numerical data ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Tertiary Care Centers ; Treatment Outcome ; }, abstract = {BACKGROUND: Severe and fulminant Clostridioides difficile infection is associated with high mortality rates. While faecal microbiota transplant has been shown to be effective for recurrent C difficile infection, there is little data on the utility of faecal microbiota transplant in severe or fulminant C difficile infection.<br><br>AIM: To compare the outcomes of antibiotics and faecal microbiota transplantation vs antibiotics alone (standard of care) in critically ill patients with severe or fulminant C&#xa0;difficile infection.<br><br>METHODS: This was a retrospective, matched cohort study in one urban tertiary academic care centre including 48 patients hospitalised with severe or fulminant C&#xa0;difficile infection who required care in intensive care unit.<br><br>RESULTS: Patients who received faecal microbiota transplantation (n = 16) had a 77% decrease in odds for mortality (OR 0.23, 95% CI 0.06-0.97) with a number needed to treat of 3 to prevent one death.<br><br>CONCLUSIONS: Faecal microbiota transplantation provides mortality benefit over standard of care for severe and fulminant C&#xa0;difficile infection and should be considered in critically ill patients.}, }
@article {pmid31611298, year = {2020}, author = {Ng, SC and Kamm, MA and Yeoh, YK and Chan, PKS and Zuo, T and Tang, W and Sood, A and Andoh, A and Ohmiya, N and Zhou, Y and Ooi, CJ and Mahachai, V and Wu, CY and Zhang, F and Sugano, K and Chan, FKL}, title = {Scientific frontiers in faecal microbiota transplantation: joint document of Asia-Pacific Association of Gastroenterology (APAGE) and Asia-Pacific Society for Digestive Endoscopy (APSDE).}, journal = {Gut}, volume = {69}, number = {1}, pages = {83-91}, pmid = {31611298}, issn = {1468-3288}, mesh = {Anti-Bacterial Agents/pharmacology ; Clostridioides difficile ; Endoscopy, Gastrointestinal ; Enterocolitis, Pseudomembranous/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects/physiology ; Humans ; Inflammatory Bowel Diseases/therapy ; Prognosis ; Recurrence ; Tissue Donors ; Treatment Outcome ; }, abstract = {OBJECTIVE: The underlying microbial basis, predictors of therapeutic outcome and active constituent(s) of faecal microbiota transplantation (FMT) mediating benefit remain unknown. An international panel of experts presented key elements that will shape forthcoming FMT research and practice.<br><br>DESIGN: Systematic search was performed, FMT literature was critically appraised and a 1-day round-table discussion was conducted to derive expert consensus on key issues in FMT research.<br><br>RESULTS: 16 experts convened and discussed five questions regarding (1) the role of donor and recipient microbial (bacteria, viruses, fungi) parameters in FMT; (2) methods to assess microbiota alterations; (3) concept of keystone species and microbial predictors of FMT, (4) influence of recipient profile and antibiotics pretreatment on FMT engraftment and maintenance and (5) new developments in FMT formulations and delivery. The panel considered that variable outcomes of FMT relate to compositional and functional differences in recipient's microbiota, and likely donor-associated and recipient-associated physiological and genetic factors. Taxonomic composition of donor intestinal microbiota may influence the efficacy of FMT in recurrent Clostridioides difficile infections and UC. FMT not only alters bacteria composition but also establishes trans-kingdom equilibrium between gut fungi, viruses and bacteria to promote the recovery of microbial homeostasis. FMT is not a one size fits all and studies are required to identify microbial components that have specific effects in patients with different diseases.<br><br>CONCLUSION: FMT requires optimisation before their therapeutic promise can be evaluated for different diseases. This summary will guide future directions and priorities in advancement of the science and practice of FMT.}, }
@article {pmid31611297, year = {2020}, author = {Olsson, LM and Poitou, C and Tremaroli, V and Coupaye, M and Aron-Wisnewsky, J and Bäckhed, F and Clément, K and Caesar, R}, title = {Gut microbiota of obese subjects with Prader-Willi syndrome is linked to metabolic health.}, journal = {Gut}, volume = {69}, number = {7}, pages = {1229-1238}, pmid = {31611297}, issn = {1468-3288}, mesh = {Adult ; Animals ; Case-Control Studies ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/genetics/physiology ; Glucose/metabolism ; Humans ; Male ; Mice ; Obesity/complications/metabolism/*microbiology ; Prader-Willi Syndrome/complications/metabolism/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVE: The gut microbiota has been implicated in the aetiology of obesity and associated comorbidities. Patients with Prader-Willi syndrome (PWS) are obese but partly protected against insulin resistance. We hypothesised that the gut microbiota of PWS patients differs from that of non-genetically obese controls and correlate to metabolic health. Therefore, here we used PWS as a model to study the role of gut microbiota in the prevention of metabolic complications linked to obesity.<br><br>DESIGN: We conducted a case-control study with 17 adult PWS patients and 17 obese subjects matched for body fat mass index, gender and age. The subjects were metabolically characterised and faecal microbiota was profiled by 16S ribosomal RNA gene sequencing. The patients' parents were used as a non-obese control group. Stool samples from two PWS patients and two obese controls were used for faecal microbiota transplantations in germ-free mice to examine the impact of the microbiota on glucose metabolism.<br><br>RESULTS: The composition of the faecal microbiota in patients with PWS differed from that of obese controls, and was characterised by higher phylogenetic diversity and increased abundance of several taxa such as Akkermansia, Desulfovibrio and Archaea, and decreased abundance of Dorea. Microbial taxa prevalent in the PWS microbiota were associated with markers of insulin sensitivity. Improved insulin resistance of PWS was partly transmitted by faecal microbiota transplantations into germ-free mice.<br><br>CONCLUSION: The gut microbiota of PWS patients is similar to that of their non-obese parents and might play a role for the protection of PWS patients from metabolic complications.}, }
@article {pmid31610731, year = {2019}, author = {Duan, Y and Prasad, R and Feng, D and Beli, E and Li Calzi, S and Longhini, ALF and Lamendella, R and Floyd, JL and Dupont, M and Noothi, SK and Sreejit, G and Athmanathan, B and Wright, J and Jensen, AR and Oudit, GY and Markel, TA and Nagareddy, PR and Obukhov, AG and Grant, MB}, title = {Bone Marrow-Derived Cells Restore Functional Integrity of the Gut Epithelial and Vascular Barriers in a Model of Diabetes and ACE2 Deficiency.}, journal = {Circulation research}, volume = {125}, number = {11}, pages = {969-988}, pmid = {31610731}, issn = {1524-4571}, support = {R01 HL137799/HL/NHLBI NIH HHS/United States ; R01 EY012601/EY/NEI NIH HHS/United States ; R01 HL115140/HL/NHLBI NIH HHS/United States ; P30 DK079626/DK/NIDDK NIH HHS/United States ; T32 HL134640/HL/NHLBI NIH HHS/United States ; P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY025383/EY/NEI NIH HHS/United States ; K99 HL122505/HL/NHLBI NIH HHS/United States ; R01 EY028037/EY/NEI NIH HHS/United States ; R01 EY028858/EY/NEI NIH HHS/United States ; R00 HL122505/HL/NHLBI NIH HHS/United States ; T32 HL105349/HL/NHLBI NIH HHS/United States ; }, mesh = {ADP-Ribosylation Factor 6 ; Adherens Junctions/metabolism ; Angiotensin-Converting Enzyme 2 ; Animals ; Bacteria/*metabolism ; *Bone Marrow Transplantation ; *Capillary Permeability ; Cells, Cultured ; Diabetes Mellitus, Type 2/enzymology/microbiology/physiopathology/*surgery ; Disease Models, Animal ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Inflammation Mediators/metabolism ; Intestinal Mucosa/*blood supply/metabolism/*microbiology/pathology ; Intestine, Small/*blood supply/enzymology/*microbiology/pathology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; *Neovascularization, Physiologic ; Peptidoglycan/metabolism ; Peptidyl-Dipeptidase A/*deficiency/genetics ; Recovery of Function ; }, abstract = {RATIONALE: There is incomplete knowledge of the impact of bone marrow cells on the gut microbiome and gut barrier function.<br><br>OBJECTIVE: We postulated that diabetes mellitus and systemic ACE2 (angiotensin-converting enzyme 2) deficiency would synergize to adversely impact both the microbiome and gut barrier function.<br><br>METHODS AND RESULTS: Bacterial 16S rRNA sequencing and metatranscriptomic analysis were performed on fecal samples from wild-type, ACE2[-/y], Akita (type 1 diabetes mellitus), and ACE2[-/y]-Akita mice. Gut barrier integrity was assessed by immunofluorescence, and bone marrow cell extravasation into the small intestine was evaluated by flow cytometry. In the ACE2[-/y]-Akita or Akita mice, the disrupted barrier was associated with reduced levels of myeloid angiogenic cells, but no increase in inflammatory monocytes was observed within the gut parenchyma. Genomic and metatranscriptomic analysis of the microbiome of ACE2[-/y]-Akita mice demonstrated a marked increase in peptidoglycan-producing bacteria. When compared with control cohorts treated with saline, intraperitoneal administration of myeloid angiogenic cells significantly decreased the microbiome gene expression associated with peptidoglycan biosynthesis and restored epithelial and endothelial gut barrier integrity. Also indicative of diabetic gut barrier dysfunction, increased levels of peptidoglycan and FABP-2 (intestinal fatty acid-binding protein 2) were observed in plasma of human subjects with type 1 diabetes mellitus (n=21) and type 2 diabetes mellitus (n=23) compared with nondiabetic controls (n=23). Using human retinal endothelial cells, we determined that peptidoglycan activates a noncanonical TLR-2 (Toll-like receptor 2) associated MyD88 (myeloid differentiation primary response protein 88)-ARNO (ADP-ribosylation factor nucleotide-binding site opener)-ARF6 (ADP-ribosylation factor 6) signaling cascade, resulting in destabilization of p120-catenin and internalization of VE-cadherin as a mechanism of deleterious impact of peptidoglycan on the endothelium.<br><br>CONCLUSIONS: We demonstrate for the first time that the defect in gut barrier function and dysbiosis in ACE2[-/y]-Akita mice can be favorably impacted by exogenous administration of myeloid angiogenic cells.}, }
@article {pmid31610229, year = {2019}, author = {Vezza, T and Rodríguez-Nogales, A and Algieri, F and Garrido-Mesa, J and Romero, M and Sánchez, M and Toral, M and Martín-García, B and Gómez-Caravaca, AM and Arráez-Román, D and Segura-Carretero, A and Micol, V and García, F and Utrilla, MP and Duarte, J and Rodríguez-Cabezas, ME and Gálvez, J}, title = {The metabolic and vascular protective effects of olive (Olea europaea L.) leaf extract in diet-induced obesity in mice are related to the amelioration of gut microbiota dysbiosis and to its immunomodulatory properties.}, journal = {Pharmacological research}, volume = {150}, number = {}, pages = {104487}, doi = {10.1016/j.phrs.2019.104487}, pmid = {31610229}, issn = {1096-1186}, mesh = {Adipogenesis/drug effects/genetics ; Adipose Tissue/drug effects/metabolism ; Animals ; Anti-Obesity Agents/pharmacology/*therapeutic use ; Aorta, Thoracic/drug effects/physiology ; Cytokines/genetics ; Diet, High-Fat ; Dysbiosis/*drug therapy/metabolism/microbiology ; Gastrointestinal Microbiome/drug effects ; Immunologic Factors/pharmacology/*therapeutic use ; Insulin Resistance ; Lipids/blood ; Liver/drug effects/metabolism ; Male ; Mice, Inbred C57BL ; NADPH Oxidases/metabolism ; Obesity/*drug therapy/metabolism/microbiology ; *Olea ; Phytotherapy ; Plant Extracts/pharmacology/*therapeutic use ; Plant Leaves ; }, abstract = {INTRODUCTION: Many studies have showed the beneficial effects of the olive (Olea europaea) leaf extract (OLE) in experimental models of metabolic syndrome, which have been ascribed to the presence of phenolic compounds, like oleuropeoside. This study evaluated the effects of a chemically characterized OLE in high fat diet (HFD)-induced obesity in mice, describing the underlying mechanisms involved in the beneficial effects, with special attention to vascular dysfunction and gut microbiota composition.<br><br>METHODS: C57BL/6J mice were distributed in different groups: control, control-treated, obese and obese-treated with OLE (1, 10 and 25&#x202f;mg/kg/day). Control mice received a standard diet, whereas obese mice were fed HFD. The treatment was followed for 5 weeks, and animal body weight periodically assessed. At the end of the treatment, metabolic plasma analysis (including lipid profile) as well as glucose and insulin levels were performed. The HFD-induced inflammatory status was studied in liver and fat, by determining the RNA expression of different inflammatory mediators by qPCR; also, different markers of intestinal epithelial barrier function were determined in colonic tissue by qPCR. Additionally, flow cytometry of immune cells from adipose tissue, endothelial dysfunction in aortic rings as well as gut microbiota composition were evaluated. Faecal microbiota transplantation (FMT) to antibiotic-treated mice fed with HFD was performed.<br><br>RESULTS: OLE administration reduced body weight gain, basal glycaemia and insulin resistance, and showed improvement in plasma lipid profile when compared with HFD-fed mice. The extract significantly ameliorated the HFD-induced altered expression of key adipogenic genes, like PPARs, adiponectin and leptin receptor, in adipose tissue. Furthermore, the extract reduced the RNA expression of Tnf-&#x3b1;, Il-1&#x3b2;, Il-6 in liver and adipose tissue, thus improving the tissue inflammatory status associated to obesity. The flow cytometry analysis in adipose tissue corroborated these observations. Additionally, the characterization of the colonic microbiota by sequencing showed that OLE administration was able to counteract the dysbiosis associated to obesity. The extract reversed the endothelial dysfunction observed in the aortic rings of obese mice. FMT from donors HFD-OLE to recipient mice fed an HFD prevented the development of obesity, glucose intolerance, insulin resistance and endothelial dysfunction.<br><br>CONCLUSION: OLE exerts beneficial effects in HFD-induced obesity in mice, which was associated to an improvement in plasma and tissue metabolic profile, inflammatory status, gut microbiota composition and vascular dysfunction.}, }
@article {pmid31609734, year = {2020}, author = {Abu-Sbeih, H and Ali, FS and Wang, Y}, title = {Immune-checkpoint inhibitors induced diarrhea and colitis: a review of incidence, pathogenesis and management.}, journal = {Current opinion in gastroenterology}, volume = {36}, number = {1}, pages = {25-32}, doi = {10.1097/MOG.0000000000000593}, pmid = {31609734}, issn = {1531-7056}, mesh = {Colitis/*chemically induced/diagnosis/epidemiology/therapy ; Diarrhea/*chemically induced/diagnosis/epidemiology/therapy ; Humans ; Immune Checkpoint Inhibitors/*adverse effects/therapeutic use ; Incidence ; Neoplasms/*drug therapy ; }, abstract = {PURPOSE OF REVIEW: Diarrhea and colitis are among the most commonly encountered immune-mediated adverse events among patients receiving antiprogrammed cell death protein/ligand-1 (PD-1/L1) as well as anticytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies. With growing indications and widespread use of immune checkpoint inhibitors, it is imperative to summarize the current body of evidence concerning the incidence, pathogenesis, risk factors, diagnostic challenges, and treatment options currently available for the management of immune-mediated diarrhea and colitis. Additionally, with emerging evidence analyzing the resumption of immune checkpoint inhibitors, it is pivotal to summarize our current understanding and future challenges.<br><br>RECENT FINDINGS: Immune-mediated diarrhea and colitis can potentially be a viable surrogate marker for improved survival as it is validated further in large-scale studies. Early endoscopic evaluation can aid in the identification of patients at risk of developing steroid refractory immune-mediated colitis, and hence can be chosen to receive early add-on therapy with infliximab, vedolizumab or fecal microbiota transplantation, an emerging treatment option for immune-mediated diarrhea and colitis. Resuming immune checkpoint inhibitors carries a manageable risk of recurrent diarrhea and colitis, with most cases being mild and effectively managed with immunosuppressive therapy.<br><br>SUMMARY: As our understanding of immune-mediated diarrhea and colitis grows, it is likely that this clinicopathologic entity will represent more than just an adverse event. With a growing number of treatment options, the management algorithms for immune-mediated diarrhea/colitis are likely to evolve in the future.}, }
@article {pmid31609702, year = {2019}, author = {Van Laar, T and Boertien, JM and Herranz, AH}, title = {Faecal Transplantation, Pro- and Prebiotics in Parkinson's Disease; Hope or Hype?.}, journal = {Journal of Parkinson's disease}, volume = {9}, number = {s2}, pages = {S371-S379}, pmid = {31609702}, issn = {1877-718X}, mesh = {Dysbiosis/diet therapy/*therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Parkinson Disease/diet therapy/*microbiology/*therapy ; *Prebiotics ; Probiotics/*pharmacology ; }, abstract = {Faecal microbiome transplantation (FMT) is an attractive technique, because the administration is relatively simple and in general has a mild adverse effect pattern. Moreover, FMT consists of a broad mixture, which could be beneficial, because at this moment it is not known what type of changes in the microbiome are needed. However, except from a few cases no clinical data in Parkinson's disease (PD) is available yet. There is some indication that FMT might be beneficial in severe constipated PD patients, but the clinical data to support this are very scarce. So, actually there are no good data in the public domain to support FMT at this moment in PD patients. FMT at this moment is a black box with too many unanswered questions, also with respect to safety concerns. Only the administration of species of Lactobacillus and Bifidobacterium over a time period of four to twelve weeks has repeatedly proven to be effective in treating constipation in PD. Also, no solid clinical data are available about the possible effects of probiotic treatment on motor symptoms or progression of PD. Therefore, also probiotic treatments in PD should wait until better clinical data become available, in order to select the right target populations and to have good estimates of the clinical effects to be expected.}, }
@article {pmid31609455, year = {2019}, author = {Bruno, G and Gagliardi, A and Oliva, A and Trancassini, M and Macone, A and Cicerone, C and D'Abramo, A and Iebba, V and Auria, S and Bonfiglio, G and Zingaropoli, MA and D'Ettorre, G and Badiali, D and Vullo, V and Corazziari, ES and Schippa, S}, title = {Fecal Microbial Transplantation impact on gut microbiota composition and metabolome, microbial translocation and T-lymphocyte immune activation in recurrent Clostridium difficile infection patients.}, journal = {The new microbiologica}, volume = {42}, number = {4}, pages = {221-224}, pmid = {31609455}, issn = {1121-7138}, mesh = {Aged ; Aged, 80 and over ; *Clostridioides difficile ; *Clostridium Infections/immunology/microbiology/therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; *Metabolome ; Middle Aged ; Recurrence ; *T-Lymphocytes/immunology ; Treatment Outcome ; }, abstract = {This short communication reports the preliminary results of Fecal Microbial Transplantation (FMT) impact on microbiota, microbial translocation (MT), and immune activation in four recurrent Clostridium difficile infection (R-CDI) patients. After FMT a restore of gut microbiota composition with a significant increase of fecal acetyl-putrescine and spermidine and fecal acetate and butyrate, a decrease of immune activation of T cells CD4+ and CD8+levels, and of LPS binding protein (LBP) level, were observed. Preliminary results indicate that FMT seems to be helpful not only as a CDI radical cure, with an impact on fecal microbiota and metabolome profiles, but also on MT and immune activation.}, }
@article {pmid31607571, year = {2019}, author = {Lin, TC and Hung, YP and Ko, WC and Ruan, JW}, title = {Fecal microbiota transplantation for Clostridium difficile infection in Taiwan: Establishment and implementation.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {52}, number = {6}, pages = {841-850}, doi = {10.1016/j.jmii.2019.08.009}, pmid = {31607571}, issn = {1995-9133}, mesh = {Clostridium Infections/*therapy ; Consensus ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Practice Guidelines as Topic ; Recurrence ; Secondary Prevention ; Taiwan ; Treatment Outcome ; }, abstract = {Clostridium difficile infection (CDI) remains a major public health issue, and fecal microbiota transplantation (FMT) has become one of the standard therapies for recurrent or refractory CDI. When compared to medical therapies, such as metronidazole or vancomycin, FMT has a high rate of treatment response with acceptable safety and efficiency. Following promulgation of the amendments in September 2018 in Taiwan, FMT has been indicated for recurrent or refractory CDI. The Taiwan Microbiota Consortium contributed to the Taiwan FMT Expert Consensus, which established basic norms and stipulated essential principles, including the indications for transplantation, eligible locations and personnel, donor screening policies, fecal sample handling, and post-FMT follow-up. However, establishing an eligible FMT team in a qualified hospital remains a clinical challenge, and the requirement for facilities and well-screened donors impedes the implementation of FMT. In this review, we aim to provide domestic FMT teams with explicit instructions to facilitate realization and increase the practice of FMT. Based on the Taiwan FMT Expert Consensus and current regulations, we performed a literature review and integrated the experiences of Taiwanese multidisciplinary experts into this article. The content intends to offer clinicians up-to-date evidence and highlight the essential points of FMT.}, }
@article {pmid31607511, year = {2019}, author = {Shi, Z and Zou, J and Zhang, Z and Zhao, X and Noriega, J and Zhang, B and Zhao, C and Ingle, H and Bittinger, K and Mattei, LM and Pruijssers, AJ and Plemper, RK and Nice, TJ and Baldridge, MT and Dermody, TS and Chassaing, B and Gewirtz, AT}, title = {Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection.}, journal = {Cell}, volume = {179}, number = {3}, pages = {644-658.e13}, pmid = {31607511}, issn = {1097-4172}, support = {R01 AI038296/AI/NIAID NIH HHS/United States ; R01 DK083890/DK/NIDDK NIH HHS/United States ; R01 DK099071/DK/NIDDK NIH HHS/United States ; R37 AI038296/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptive Immunity/*genetics ; Animals ; Anti-Infective Agents/pharmacology ; Bacteria/genetics/metabolism ; Diarrhea/*microbiology/prevention &amp; control/virology ; Feces/microbiology ; Gene Expression Regulation/genetics ; Humans ; Ileum/microbiology/pathology/virology ; Interferons/genetics ; Interleukin-17/genetics ; Interleukins/genetics ; Intestinal Mucosa/*microbiology/pathology/virology ; Mice ; Microbiota/genetics ; Rotavirus/pathogenicity ; Rotavirus Infections/*microbiology/prevention &amp; control/virology ; Interleukin-22 ; }, abstract = {Rotavirus (RV) encounters intestinal epithelial cells amidst diverse microbiota, opening possibilities of microbes influencing RV infection. Although RV clearance typically requires adaptive immunity, we unintentionally generated RV-resistant immunodeficient mice, which, we hypothesized, reflected select microbes protecting against RV. Accordingly, such RV resistance was transferred by co-housing and fecal transplant. RV-protecting microbiota were interrogated by heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germ-free mice and microbiome analysis. This approach revealed that segmented filamentous bacteria (SFB) were sufficient to protect mice against RV infection and associated diarrhea. Such protection was independent of previously defined RV-impeding factors, including interferon, IL-17, and IL-22. Colonization of the ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover. Incubation of RV with SFB-containing feces reduced infectivity in vitro, suggesting direct neutralization of RV. Thus, independent of immune cells, SFB confer protection against certain enteric viral infections and associated diarrheal disease.}, }
@article {pmid31606552, year = {2020}, author = {Chu, H and Duan, Y and Lang, S and Jiang, L and Wang, Y and Llorente, C and Liu, J and Mogavero, S and Bosques-Padilla, F and Abraldes, JG and Vargas, V and Tu, XM and Yang, L and Hou, X and Hube, B and Stärkel, P and Schnabl, B}, title = {The Candida albicans exotoxin candidalysin promotes alcohol-associated liver disease.}, journal = {Journal of hepatology}, volume = {72}, number = {3}, pages = {391-400}, pmid = {31606552}, issn = {1600-0641}, support = {R01 AA020703/AA/NIAAA NIH HHS/United States ; I01 BX004594/BX/BLRD VA/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; U01 AA026939/AA/NIAAA NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Candida albicans/*metabolism ; Case-Control Studies ; Cells, Cultured ; Disease Models, Animal ; Exotoxins/analysis/*metabolism/pharmacology ; Feces/microbiology ; Female ; Fungal Proteins/analysis/*metabolism/pharmacology ; Gastrointestinal Microbiome ; Hepatitis, Alcoholic/*metabolism/*microbiology/mortality ; Hepatocytes/drug effects ; Humans ; Lectins, C-Type/deficiency/genetics ; Liver Diseases, Alcoholic/*metabolism/*microbiology/mortality ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Severity of Illness Index ; }, abstract = {BACKGROUND &amp; AIMS: Alcohol-associated liver disease is a leading indication for liver transplantation and a leading cause of mortality. Alterations to the gut microbiota contribute to the pathogenesis of alcohol-associated liver disease. Patients with alcohol-associated liver disease have increased proportions of Candida spp. in the fecal mycobiome, yet little is known about the effect of intestinal Candida on the disease. Herein, we evaluated the contributions of Candida albicans and its exotoxin candidalysin in alcohol-associated liver disease.<br><br>METHODS: C. albicans and the extent of cell elongation 1 (ECE1) were analyzed in fecal samples from controls, patients with alcohol use disorder and those with alcoholic hepatitis. Mice colonized with different and genetically manipulated C. albicans strains were subjected to the chronic-plus-binge ethanol diet model. Primary hepatocytes were isolated and incubated with candidalysin.<br><br>RESULTS: The percentages of individuals carrying ECE1 were 0%, 4.76% and 30.77% in non-alcoholic controls, patients with alcohol use disorder and patients with alcoholic hepatitis, respectively. Candidalysin exacerbates ethanol-induced liver disease and is associated with increased mortality in mice. Candidalysin enhances ethanol-induced liver disease independently of the &#x3b2;-glucan receptor C-type lectin domain family 7 member A (CLEC7A) on bone marrow-derived cells, and candidalysin does not alter gut barrier function. Candidalysin can damage primary hepatocytes in a dose-dependent manner in vitro and is associated with liver disease severity and mortality in patients with alcoholic hepatitis.<br><br>CONCLUSIONS: Candidalysin is associated with the progression of ethanol-induced liver disease in preclinical models and worse clinical outcomes in patients with alcoholic hepatitis.<br><br>LAY SUMMARY: Candidalysin is a peptide toxin secreted by the commensal gut fungus Candida albicans. Candidalysin enhances alcohol-associated liver disease independently of the &#x3b2;-glucan receptor CLEC7A on bone marrow-derived cells in mice without affecting intestinal permeability. Candidalysin is cytotoxic to primary hepatocytes, indicating a direct role of candidalysin on ethanol-induced liver disease. Candidalysin might be an effective target for therapy in patients with alcohol-associated liver disease.}, }
@article {pmid31606301, year = {2019}, author = {Evrensel, A and Ceylan, ME}, title = {Editorial overview: The gut microbiome: Its role in disorders of the GI tract and metabolic homeostasis.}, journal = {Current opinion in pharmacology}, volume = {49}, number = {}, pages = {iii-v}, doi = {10.1016/j.coph.2019.09.001}, pmid = {31606301}, issn = {1471-4973}, mesh = {Animals ; Fecal Microbiota Transplantation/adverse effects/economics/ethics ; Gastrointestinal Diseases/*microbiology/therapy ; *Gastrointestinal Microbiome ; Homeostasis ; Humans ; Metabolic Diseases/*microbiology/therapy ; Probiotics ; }, }
@article {pmid31601212, year = {2019}, author = {Madar, PC and Petre, O and Baban, A and Dumitrascu, DL}, title = {Medical students' perception on fecal microbiota transplantation.}, journal = {BMC medical education}, volume = {19}, number = {1}, pages = {368}, pmid = {31601212}, issn = {1472-6920}, mesh = {Cross-Sectional Studies ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*statistics &amp; numerical data ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; *Internship and Residency ; Male ; Practice Patterns, Physicians'/*statistics &amp; numerical data ; *Students, Medical ; Surveys and Questionnaires ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has become an emergent method in the therapy of several intestinal diseases, mainly in Clostridium difficile recurrence. The training of FMT in medical schools is at its beginning and in countries where FMT is only occasionally carried out, it is important to know the perception of medical students on FMT.<br><br>METHODS: We undertook a survey of 3rd year medical students not exposed to official academic information on FMT in order to find out their knowledge, beliefs and attitude toward FMT. A number of 80 students were asked to fill a dedicated online questionnaire.<br><br>RESULTS: 52 out of 80 third year medical students anonymously filled the questionnaire (65% response rate). 34% of respondents reported to have at least a medium level of knowledge regarding FMT. The top indication for FMT identified by 76.9% was C. difficile infection; however, 60% believed FMT to be a promising therapy for a high number of conditions and while almost all respondents (98.1%) would recommend it, 88.4% would explore other options first. Colonoscopy was considered the optimal method of delivery by 42.3%. Only 39% of participants believed that patients would accept FMT, however 71% considered that a more socially acceptable name for the procedure and anonymous donors would increase acceptance rate. The risk of transmitting a disease undetected by donor stool screening procedures to the recipient was the most worrying side effect considered by 75% of respondents. 54% believed that more research is required for FMT to enter clinical practice and 55.7% of respondents would enroll patients in controlled clinical trials.<br><br>CONCLUSIONS: Medical students not exposed to educational information on FMT seem to be somewhat well informed about this method and would recommend it to their patients. Students, however, need to know more on the indications of FMT.}, }
@article {pmid31600750, year = {2020}, author = {Zhong, F and Zhou, X and Xu, J and Gao, L}, title = {Rodent Models of Nonalcoholic Fatty Liver Disease.}, journal = {Digestion}, volume = {101}, number = {5}, pages = {522-535}, doi = {10.1159/000501851}, pmid = {31600750}, issn = {1421-9867}, mesh = {Animals ; Antioxidants/therapeutic use ; Carbon Tetrachloride/administration &amp; dosage/toxicity ; Cholesterol, Dietary/adverse effects ; Combined Modality Therapy ; Diet, Carbohydrate Loading/adverse effects ; Diet, High-Fat/adverse effects ; *Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/physiology ; Humans ; Insulin/therapeutic use ; Lipid Metabolism/genetics ; Liver/drug effects/metabolism/*pathology ; Liver Cirrhosis/pathology/*prevention &amp; control ; Mice ; Mice, Knockout ; Mice, Obese ; Non-alcoholic Fatty Liver Disease/etiology/pathology/*therapy ; Probiotics/administration &amp; dosage ; Rats ; Rats, Transgenic ; Streptozocin/administration &amp; dosage/toxicity ; Tetracycline/administration &amp; dosage/toxicity ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) is a continuous diseases spectrum associated with obesity, type 2 diabetes, insulin resistance, and hyperlipidemia. Simple hepatic steatosis may progress to nonalcoholic steatohepatitis (NASH), even fibrosis and cirrhosis, and finally hepatocellular carcinoma. In recent years, NAFLD has become a public health concern with increasing prevalence. However, the mechanisms underlying the pathogenesis remain incompletely understood, and few effective therapeutic approaches are available. Summary and Key Messages: A myriad of different rodent models has been developed to elucidate pathophysiology of NAFLD/NASH and guide therapeutic strategy. To date, no single rodent model can display the whole disease spectrum and metabolic features associated with human NASH, but can imitate particular characteristics. In this paper, we review the most commonly used dietary, genetic, and chemical rodent models for NAFLD referring to their advantages and disadvantages. Also, we illustrate the status of latest treatment strategy using various NAFLD rodent models. We hope to provide critical guidance for researchers to select appropriate animal models.}, }
@article {pmid31600222, year = {2019}, author = {Duvallet, C and Zellmer, C and Panchal, P and Budree, S and Osman, M and Alm, EJ}, title = {Framework for rational donor selection in fecal microbiota transplant clinical trials.}, journal = {PloS one}, volume = {14}, number = {10}, pages = {e0222881}, pmid = {31600222}, issn = {1932-6203}, mesh = {Clostridioides difficile/growth &amp; development/pathogenicity ; Clostridium Infections/microbiology/*therapy ; Donor Selection/*methods ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/*microbiology ; Gastrointestinal Microbiome/genetics ; Humans ; Microbiota/genetics ; Retrospective Studies ; }, abstract = {Early clinical successes are driving enthusiasm for fecal microbiota transplantation (FMT), the transfer of healthy gut bacteria through whole stool, as emerging research is linking the microbiome to many different diseases. However, preliminary trials have yielded mixed results and suggest that heterogeneity in donor stool may play a role in patient response. Thus, clinical trials may fail because an ineffective donor was chosen rather than because FMT is not appropriate for the indication. Here, we describe a conceptual framework to guide rational donor selection to increase the likelihood that FMT clinical trials will succeed. We argue that the mechanism by which the microbiome is hypothesized to be associated with a given indication should inform how healthy donors are selected for FMT trials, categorizing these mechanisms into four disease models and presenting associated donor selection strategies. We next walk through examples based on previously published FMT trials and ongoing investigations to illustrate how donor selection might occur in practice. Finally, we show that typical FMT trials are not powered to discover individual taxa mediating patient responses, suggesting that clinicians should develop targeted hypotheses for retrospective analyses and design their clinical trials accordingly. Moving forward, developing and applying novel clinical trial design methodologies like rational donor selection will be necessary to ensure that FMT successfully translates into clinical impact.}, }
@article {pmid31599752, year = {2020}, author = {Shah, H and Zezos, P}, title = {Pouchitis: diagnosis and management.}, journal = {Current opinion in gastroenterology}, volume = {36}, number = {1}, pages = {41-47}, doi = {10.1097/MOG.0000000000000594}, pmid = {31599752}, issn = {1531-7056}, mesh = {Humans ; Pouchitis/*diagnosis/etiology/*therapy ; Proctocolectomy, Restorative/*adverse effects ; }, abstract = {PURPOSE OF REVIEW: Pouchitis is the most common complication in patients who undergo ileal pouch-anal anastomosis (IPAA), occurring more frequently in patients with ulcerative colitis. Pouchitis - the inflammation of the pouch - can be due to idiopathic or secondary causes. Chronic antibiotic-dependent pouchitis (CADP) and chronic antibiotic-resistant pouchitis (CARP) are the most difficult forms of chronic idiopathic pouchitis to treat. Crohn's disease of the pouch may develop de novo in ulcerative colitis patients following colectomy with IPAA. It carries a high risk for pouch failure, and its diagnosis and management are challenging. The purpose of this review is to illustrate the present trends in the diagnosis and treatment of idiopathic pouchitis and Crohn's disease of the pouch.<br><br>RECENT FINDINGS: The use of the newer biologic agents, vedolizumab and ustekinumab, has shown promising results in patients with CADP, CARP, and Crohn's disease of the pouch. Fecal microbiota transplantation has also been reported to have encouraging preliminary results in small studies and case series for the treatment of chronic pouchitis.<br><br>SUMMARY: Promising new treatments are emerging for difficult-to-treat forms of pouchitis. Larger prospective and head-to-head comparative studies among the various treatments are needed to evaluate the efficacy and safety of these agents across the pouchitis subgroups, and to identify predictors of response.}, }
@article {pmid31597716, year = {2019}, author = {Collins, MG and Symonds, EL and Bampton, PA and Coates, PT}, title = {Fecal Immunochemical Screening for Advanced Colorectal Neoplasia in Patients with CKD: Accurate or Not?.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {30}, number = {11}, pages = {2275}, pmid = {31597716}, issn = {1533-3450}, mesh = {*Colorectal Neoplasms ; Feces ; Humans ; Mass Screening ; *Renal Insufficiency, Chronic ; }, }
@article {pmid31597320, year = {2019}, author = {Holster, S and Hooiveld, GJ and Repsilber, D and Vos, WM and Brummer, RJ and König, J}, title = {Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome.}, journal = {Biomolecules}, volume = {9}, number = {10}, pages = {}, pmid = {31597320}, issn = {2218-273X}, mesh = {Adult ; Bacteria/*classification/immunology ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome ; Gene Expression Profiling/*methods ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; *Immunity ; Intestinal Mucosa/chemistry ; Irritable Bowel Syndrome/genetics/immunology/*therapy ; Male ; Middle Aged ; Quality of Life ; Sequence Analysis, RNA ; Sigmoidoscopy ; Transplantation, Autologous ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe-host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.}, }
@article {pmid31596218, year = {2019}, author = {Mashaqi, S and Gozal, D}, title = {Obstructive Sleep Apnea and Systemic Hypertension: Gut Dysbiosis as the Mediator?.}, journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine}, volume = {15}, number = {10}, pages = {1517-1527}, pmid = {31596218}, issn = {1550-9397}, mesh = {Dysbiosis/*complications/physiopathology ; Gastrointestinal Microbiome/*physiology ; Humans ; Hypertension/*complications/*microbiology/physiopathology ; Sleep Apnea, Obstructive/*complications/*microbiology/physiopathology ; }, abstract = {INTRODUCTION: Obstructive sleep apnea (OSA) and systemic hypertension (SH) are common and interrelated diseases. It is estimated that approximately 75% of treatment-resistant hypertension cases have an underlying OSA. Exploration of the gut microbiome is a new advance in medicine that has been linked to many comorbid illnesses, including SH and OSA. Here, we will review the literature in SH and gut dysbiosis, OSA and gut dysbiosis, and whether gut dysbiosis is common in both conditions.<br><br>METHODS: We reviewed the National Center for Biotechnology Information database, including PubMed and PubMed Central. We identified a total of 230 articles. The literature search was conducted using the phrase "obstructive sleep apnea and gut dysbiosis." Only original research articles were included. This yielded a total of 12 articles.<br><br>RESULTS: Most of the research conducted in this field was on animal models, and almost all trials confirmed that intermittent hypoxia models resulted in gut dysbiosis. Gut dysbiosis, however, can cause a state of low-grade inflammation through damage to the gut wall barrier resulting in "leaky gut." Neuroinflammation is a hallmark of the pathophysiology of OSA-induced SH.<br><br>CONCLUSIONS: Gut dysbiosis seems to be an important factor in the pathophysiology of OSA-induced hypertension. Reversing gut dysbiosis at an early stage through prebiotics and probiotics and fecal microbiota transplantation combined with positive airway pressure therapy may open new horizons of treatment to prevent SH. More studies are needed in humans to elicit the effect of positive airway pressure therapy on gut dysbiosis.}, }
@article {pmid31596195, year = {2019}, author = {Lei, S and Twitchell, EL and Ramesh, AK and Bui, T and Majette, E and Tin, CM and Avery, R and Arango-Argoty, G and Zhang, L and Becker-Dreps, S and Azcarate-Peril, MA and Jiang, X and Yuan, L}, title = {Enhanced GII.4 human norovirus infection in gnotobiotic pigs transplanted with a human gut microbiota.}, journal = {The Journal of general virology}, volume = {100}, number = {11}, pages = {1530-1540}, pmid = {31596195}, issn = {1465-2099}, support = {R01 AI089634/AI/NIAID NIH HHS/United States ; R01 AI123661/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Blood/virology ; Caliciviridae Infections/complications/*pathology ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Disease Models, Animal ; Duodenum/virology ; *Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Genotype ; Germ-Free Life ; Humans ; Ileum/virology ; *Microbial Interactions ; *Microbiota ; Norovirus/classification/genetics/*growth &amp; development ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Swine ; Time Factors ; Viral Load ; Virus Shedding ; }, abstract = {The role of commensal microbiota in enteric viral infections has been explored extensively, but the interaction between human gut microbiota (HGM) and human norovirus (HuNoV) is poorly understood. In this study, we established an HGM-Transplanted gnotobiotic (Gn) pig model of HuNoV infection and disease, using an infant stool as HGM transplant and a HuNoV GII.4/2006b strain for virus inoculation. Compared to germ-free Gn pigs, HuNoV inoculation in HGMT Gn pigs resulted in increased HuNoV shedding, characterized by significantly higher shedding titres on post inoculation day (PID) 3, 4, 6, 8 and 9, and significantly longer mean duration of virus shedding. In addition, virus titres were significantly higher in duodenum and distal ileum of HGMT Gn pigs on PID10, while comparable and transient HuNoV viremia was detected in both groups. 16S rRNA gene sequencing demonstrated that HuNoV infection dramatically altered intestinal microbiota in HGMT Gn pigs at the phylum (Proteobacteria, Firmicutes and Bacteroidetes) and genus (Enterococcus, Bifidobacterium, Clostridium, Ruminococcus, Anaerococcus, Bacteroides and Lactobacillus) levels. In summary, enhanced GII.4 HuNoV infection was observed in the presence of HGM, and host microbiota was susceptible to disruption upon HuNoV infection.}, }
@article {pmid31594750, year = {2019}, author = {Li, L and Li, X and Zhong, W and Yang, M and Xu, M and Sun, Y and Ma, J and Liu, T and Song, X and Dong, W and Liu, X and Chen, Y and Liu, Y and Abla, Z and Liu, W and Wang, B and Jiang, K and Cao, H}, title = {Gut microbiota from colorectal cancer patients enhances the progression of intestinal adenoma in Apc[min/+] mice.}, journal = {EBioMedicine}, volume = {48}, number = {}, pages = {301-315}, pmid = {31594750}, issn = {2352-3964}, abstract = {BACKGROUND: Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma.<br><br>METHODS: The Apc[min/+] mice gavage with phosphate-buffered saline (PBS), feces from healthy controls or CRC patients after antibiotic cocktails. The intestinal tissues were isolated for histopathology, western blotting, and RNA-seq. The microbiota of feces and short-chain fatty acids (SCFAs) were analysed by 16S rDNA Amplicon Sequencing and gas chromatography.<br><br>FINDINGS: The Apc[min/+]mice gavaged by feces from CRC patients had more intestinal tumours compared with those fed with feces from healthy controls or PBS. Administration of feces from CRC patients increased tumour proliferation and decreased apoptosis in tumour cells, accompanied by impairment of gut barrier function and up-regulation the pro-inflammatory cytokines profile. The up-regulated the expression of &#x3b2;-catenin and cyclinD1 further indicating the activation of Wnt signalling pathway. The abundance of pathogenic bacteria was increased after FMT, while producing SCFAs bacteria and SCFAs production were decreased.<br><br>INTERPRETATION: Gut microbiota of CRC patients disrupted intestinal barrier, induced low-grade inflammation and dysbiosis. The altered gut microbiota enhanced the progression of intestinal adenomas in Apc[min/+]mice, suggesting that a new strategy to target gut microbiota against CRC could be noted. FUND: The study was supported by the National Natural Science Foundation of China, Tianjin Research Programme of Application Foundation and Advanced Technology of China, and China Postdoctoral Science Foundation.}, }
@article {pmid31594647, year = {2019}, author = {Benno, P and Norin, E and Midtvedt, T and Hellström, PM}, title = {Therapeutic potential of an anaerobic cultured human intestinal microbiota, ACHIM, for treatment of IBS.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {40-41}, number = {}, pages = {101607}, doi = {10.1016/j.bpg.2019.03.003}, pmid = {31594647}, issn = {1532-1916}, mesh = {Adult ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Irritable Bowel Syndrome/pathology/*therapy ; Male ; Middle Aged ; }, abstract = {By administering an anaerobic cultivated human intestinal microbiota (ACHIM) via upper gastrointestinal route using endoscopy we aimed to rectify intestinal dysbiosis and simultaneously achieve a treatment response in IBS patients. The study population fulfilled the Rome III IBS criteria and comprised 50 patients. During 10 days, patients recorded the irritable bowel syndrome symptom severity scale (IBS-SSS) along with the Bristol stool scale and number of stools/day. The enrolled patients were categorized as follows: 37 with diarrhea, 5 with constipation and 8 with mixed symptoms. The treatment response showed reduction in a majority of patients, 32 of which with 50-point reduction of IBS-SSS and 21 with a 100-point IBS-SSS reduction. The percentage improvement was 36 (23-49) and 28 (18-38) for women and men respectively. Short-chain fatty acids were not changed. We consider fecal microbiota transplantation in the form of ACHIM as an option for the future therapeutic armamentarium in IBS. REGISTERED TRIAL: www.clinicaltrials.gov NCT02857257.}, }
@article {pmid31594178, year = {2019}, author = {Yin, G and Li, JF and Sun, YF and Ding, X and Zeng, JQ and Zhang, T and Peng, LH and Yang, YS and Zhao, H}, title = {[Fecal microbiota transplantation as a novel therapy for severe psoriasis].}, journal = {Zhonghua nei ke za zhi}, volume = {58}, number = {10}, pages = {782-785}, doi = {10.3760/cma.j.issn.0578-1426.2019.10.011}, pmid = {31594178}, issn = {0578-1426}, mesh = {Adult ; Endoscopy ; *Fecal Microbiota Transplantation/trends ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Intestines ; Irritable Bowel Syndrome/complications/microbiology/psychology/*therapy ; Male ; Psoriasis/psychology/*therapy ; Quality of Life ; Treatment Outcome ; Tumor Necrosis Factor-alpha/*blood ; }, abstract = {To explore the therapeutic effect of fecal microbiota transplantation (FMT) for severe psoriasis. A patient, male, 36 years old, diagnosed as severe plaque psoriasis for 10 years and irritable bowel syndrome (IBS) for 15 years, was administrated twice FMT via both upper endoscopy and colonoscopy with a 5-week interval. The following items were used to evaluate responses: body surface area (BSA), psoriasis area and severity index (PASI), dermatology life quality index (DLQI), histological examination, intestinal symptoms, adverse reactions and serum level of tumor necrosis factor (TNF)-α. After second FMT treatment for 5 weeks, aforementioned items were improved greatly compared with those before treatment. Moreover, IBS was completely relieved and no adverse reactions were observed during the treatment and follow-up. In conclusion, FMT could be a novel therapy for psoriasis. Further clinical trials are needed to provide solid evidences.}, }
@article {pmid31593782, year = {2020}, author = {Tran, HQ and Bretin, A and Adeshirlarijaney, A and Yeoh, BS and Vijay-Kumar, M and Zou, J and Denning, TL and Chassaing, B and Gewirtz, AT}, title = {"Western Diet"-Induced Adipose Inflammation Requires a Complex Gut Microbiota.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {9}, number = {2}, pages = {313-333}, pmid = {31593782}, issn = {2352-345X}, support = {P30 DK020572/DK/NIDDK NIH HHS/United States ; R01 DK083890/DK/NIDDK NIH HHS/United States ; R01 DK099071/DK/NIDDK NIH HHS/United States ; }, mesh = {Adipocytes/immunology/metabolism ; Adipose Tissue/*immunology/pathology ; Adiposity/*immunology ; Animals ; Diet, High-Fat/adverse effects ; Diet, Western/*adverse effects ; Disease Models, Animal ; Endoplasmic Reticulum Stress/immunology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*immunology ; Humans ; Inflammation/immunology/microbiology ; Macrophages/immunology ; Male ; Metabolic Syndrome/*immunology/microbiology ; Mice ; Signal Transduction ; }, abstract = {BACKGROUND &amp; AIMS: Consumption of a low-fiber, high-fat, Western-style diet (WSD) induces adiposity and adipose inflammation characterized by increases in the M1:M2 macrophage ratio and proinflammatory cytokine expression, both of which contribute to WSD-induced metabolic syndrome. WSD-induced adipose inflammation might result from endoplasmic reticulum stress in lipid-overloaded adipocytes and/or dissemination of gut bacterial products, resulting in activation of innate immune signaling. Hence, we aimed to investigate the role of the gut microbiota, and its detection by innate immune signaling pathways, in WSD-induced adipose inflammation.<br><br>METHODS: Mice were fed grain-based chow or a WSD for 8 weeks, assessed metabolically, and intestinal and adipose tissue were analyzed by flow cytometry and quantitative reverse transcription polymerase chain reaction. Microbiota was ablated via antibiotics and use of gnotobiotic mice that completely lacked microbiota (germ-free mice) or had a low-complexity microbiota (altered Schaedler flora). Innate immune signaling was ablated by genetic deletion of Toll-like receptor signaling adaptor myeloid differentiation primary response&#xa0;88.<br><br>RESULTS: Ablation of microbiota via antibiotic, germ-free, or altered Schaedler flora approaches did not significantly impact WSD-induced adiposity, yet dramatically reduced WSD-induced adipose inflammation as assessed by macrophage populations and cytokine expression. Microbiota ablation also prevented colonic neutrophil and CD103[-] dendritic cell infiltration. Such reduced indices of inflammation correlated with protection against WSD-induced dysglycemia, hypercholesterolemia, and liver dysfunction. Genetic deletion of myeloid differentiation primary response 88 also prevented WSD-induced adipose inflammation.<br><br>CONCLUSIONS: These results indicate that adipose inflammation, and some aspects of metabolic syndrome, are not purely a consequence of diet-induced adiposity per se but, rather, may require disturbance of intestine-microbiota interactions and subsequent activation of innate immunity.}, }
@article {pmid31592683, year = {2019}, author = {Rijkers, GT and Andriessen, SQ and van Overveld, FJ}, title = {Death and the Miser: microbiota regulate the outcome of checkpoint inhibition immunotherapy.}, journal = {Expert review of anticancer therapy}, volume = {19}, number = {10}, pages = {831-834}, doi = {10.1080/14737140.2019.1677158}, pmid = {31592683}, issn = {1744-8328}, mesh = {Animals ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunotherapy/*methods ; Neoplasms/immunology/pathology/*therapy ; }, }
@article {pmid31586663, year = {2019}, author = {Aggeletopoulou, I and Konstantakis, C and Assimakopoulos, SF and Triantos, C}, title = {The role of the gut microbiota in the treatment of inflammatory bowel diseases.}, journal = {Microbial pathogenesis}, volume = {137}, number = {}, pages = {103774}, doi = {10.1016/j.micpath.2019.103774}, pmid = {31586663}, issn = {1096-1208}, mesh = {Animals ; Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology/therapy ; }, abstract = {The human intestinal microbiota coevolves with its host through a symbiotic relationship and exerts great influence on substantial functions including aspects of physiology, metabolism, nutrition and regulation of immune responses leading to physiological homeostasis. Over the last years, several studies have been conducted toward the assessment of the host-gut microbiota interaction, aiming to elucidate the mechanisms underlying the pathogenesis of several diseases. A defect on the microbiota-host crosstalk and the concomitant dysregulation of immune responses combined with genetic and environmental factors have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). To this end, novel therapeutic options based on the gut microbiota modulation have been an area of extensive research interest. In this review we present the recent findings on the association of dysbiosis with IBD pathogenesis, we focus on the role of gut microbiota on the treatment of IBD and discuss the novel and currently available therapeutic strategies in manipulating the composition and function of gut microbiota in IBD patients. Applicable and emerging microbiota treatment modalities, such as the use of antibiotics, prebiotics, probiotics, postbiotics, synbiotics and fecal microbiota transplantation (FMT) constitute promising therapeutic options. However, the therapeutic potential of the aforementioned approaches is a topic of investigation and further studies are needed to elucidate their position in the present treatment algorithms of IBD.}, }
@article {pmid31586566, year = {2020}, author = {Song, M and Chan, AT and Sun, J}, title = {Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer.}, journal = {Gastroenterology}, volume = {158}, number = {2}, pages = {322-340}, pmid = {31586566}, issn = {1528-0012}, support = {R01 CA202704/CA/NCI NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; K01 DK075386/DK/NIDDK NIH HHS/United States ; R03 DK089010/DK/NIDDK NIH HHS/United States ; R01 CA137178/CA/NCI NIH HHS/United States ; K24 DK098311/DK/NIDDK NIH HHS/United States ; R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; K99 CA215314/CA/NCI NIH HHS/United States ; R00 CA215314/CA/NCI NIH HHS/United States ; }, mesh = {Bacteria/isolation &amp; purification ; Colon/microbiology/pathology ; Colorectal Neoplasms/diagnosis/*epidemiology/etiology/prevention &amp; control ; Early Detection of Cancer/methods ; Exercise/*physiology ; Feeding Behavior/*physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Incidence ; Intestinal Mucosa/microbiology/pathology ; Mass Screening/methods ; Risk Factors ; }, abstract = {Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal cancer (CRC). However, it is unclear whether changes in the intestinal microbiome contribute to the development of sporadic CRC or result from it. Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC. Factors that affect risk of CRC also affect the intestinal microbiome, including overweight and obesity; physical activity; and dietary intake of fiber, whole grains, and red and processed meat. These factors alter microbiome structure and function, along with the metabolic and immune pathways that mediate CRC development. We review epidemiologic and laboratory evidence for the influence of the microbiome, diet, and environmental factors on CRC incidence and outcomes. Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment. Integrated prospective studies are urgently needed to investigate these strategies.}, }
@article {pmid31583398, year = {2019}, author = {Mahida, YR}, title = {New concepts in C. difficile management.}, journal = {British medical bulletin}, volume = {131}, number = {1}, pages = {109-118}, doi = {10.1093/bmb/ldz029}, pmid = {31583398}, issn = {1471-8391}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacterial Vaccines ; *Clostridioides difficile ; Clostridium Infections/*prevention &amp; control/transmission ; Drug Therapy, Combination ; Feces/microbiology ; Humans ; Infection Control/methods ; Inflammatory Bowel Diseases/microbiology ; Recurrence ; Risk Factors ; }, abstract = {BACKGROUND: Clostridium difficile infection is transmitted via spores, and the disease is mediated via secreted toxins. It represents a significant healthcare problem, and clinical presentation can range from asymptomatic carriage to life-threatening pseudomembranous colitis.<br><br>SOURCES OF DATA: publications in the field, with a focus on recent developments and concepts.<br><br>AREAS OF AGREEMENT: infection control measures, antibiotic stewardship and current management of the initial episode of C. difficile infection.<br><br>AREAS OF CONTROVERSY: selection and sequence of interventions for the management of recurrent C. difficile infection; management of persistent carriers of toxigenic C. difficile in patients at high risk of subsequent C. difficile infection.<br><br>GROWING POINTS: use of faecal microbiota transplantation for recurrent C. difficile infection.<br><br>role of specific microbiota-mediated interventions and vaccination in the treatment and prevention of C. difficile infection.}, }
@article {pmid31582175, year = {2020}, author = {Dougé, A and Bay, JO and Ravinet, A and Scanzi, J}, title = {[Intestinal microbiota and allogeneic stem cell transplantation].}, journal = {Bulletin du cancer}, volume = {107}, number = {1}, pages = {72-83}, doi = {10.1016/j.bulcan.2019.08.014}, pmid = {31582175}, issn = {1769-6917}, mesh = {Allografts ; Clostridioides difficile ; Clostridium Infections/etiology/prevention &amp; control ; Disease Susceptibility ; Dysbiosis/etiology/microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/physiology/radiation effects ; Graft vs Host Disease/etiology/microbiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Infections/etiology ; Neoplasms/microbiology/therapy ; Recurrence ; Transplantation Conditioning/adverse effects ; }, abstract = {Allogeneic hematopoïetic stem cell transplantation is one of the most efficient curative treatment for acute leukemia. But it is also a heavy process with an important risk of complications, particularly infection and graft versus host disease. Increasing data in literature show that an alteration of the intestinal microbiota of allogeneic stem cell recipients is associated with these complications. Indeed, treatments used during conditioning regimen lead to an impaired microbiota, which cannot fulfill its protective functions anymore. To limit this microbiota impairment, we could restore a healthy microbiota by a fecal microbiota transplantation, which has already shown its efficiency in the treatment of Clostridium difficile infection. The aim of this review is to describe the intestinal microbiota, the link between microbiota and complications of allogeneic stem cells transplantation, and the recent published data on fecal microbiota transplantation in this field.}, }
@article {pmid31580234, year = {2019}, author = {Thakkar, RG and Kanwar, A and Singh, A and Hawche, G and Talbot, D and Wilson, C and Manas, DM and White, SA}, title = {Preemptive Appendicectomy at the Time of Pancreas Transplantation: Is It Necessary?.}, journal = {Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation}, volume = {17}, number = {6}, pages = {792-795}, doi = {10.6002/ect.2019.0186}, pmid = {31580234}, issn = {2146-8427}, mesh = {Adolescent ; Adult ; *Appendectomy/adverse effects ; Appendicitis/etiology/*prevention &amp; control ; Appendix/*pathology ; Databases, Factual ; Female ; Humans ; Male ; Middle Aged ; *Pancreas Transplantation/adverse effects ; Protective Factors ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVES: Pancreas transplant is a major intraabdominal operation, and in most cases the graft is placed in the rightiliac fossa. At our center, preemptive appendicectomy is performed at the time of pancreas transplant to prevent any future risk in a complex transplant patient. The aim of this study was to review all histology reports from the removed appendices.<br><br>MATERIALS AND METHODS: The histology reports from all incidental appendicectomies performed at pancreas transplant were reviewed.<br><br>RESULTS: Between January 2001 and June 2016, 107 pancreas transplants were performed (86 simultaneous pancreas and kidney transplants, 11 pancreas after kidney transplants, and 10 pancreas transplants alone), and 65 appendix histology reports were available from this patient group. All were preemptive appendicectomies as none of the patients had symptoms to suggest acute appendicitis. Of the 65 appendix histologies, 43 (66.2%) were reported as normal. Twenty specimens (30.8%) showed fibrosis consistent with previous inflammation of the appendix, and 12 specimens (18.5%) showed fecal material in the lumen (1 due to an obstructing fecalith and another 2 showing luminal distension with feces). Three specimens (4.6%) showed lymphoid hyperplasia. There were 5 (7.7 %) unexpected findings upon histology. In review of histology reports, 1 patient had a 1.1-mm carcinoid tumor in an otherwise normal appendix, 1 had an Enterobius species worm infestation, 1 had focal endometriosis, 1 had crypt abscesses suggestive of inflammatory bowel disease, 1 had a metaplastic polyp, and 1 had melanosis coli of unknown clinical significance. There were no cases of overt acute appendicitis. No patients experienced a complication as a direct result of their appendicectomy.<br><br>CONCLUSIONS: A policy ofroutine appendicectomy atthe time of pancreas transplant appears to be justified and safe.}, }
@article {pmid31578306, year = {2019}, author = {Drewes, JL and Corona, A and Sanchez, U and Fan, Y and Hourigan, SK and Weidner, M and Sidhu, SD and Simner, PJ and Wang, H and Timp, W and Oliva-Hemker, M and Sears, CL}, title = {Transmission and clearance of potential procarcinogenic bacteria during fecal microbiota transplantation for recurrent Clostridioides difficile.}, journal = {JCI insight}, volume = {4}, number = {19}, pages = {}, pmid = {31578306}, issn = {2379-3708}, support = {K99 CA230192/CA/NCI NIH HHS/United States ; T32 HD044355/HD/NICHD NIH HHS/United States ; //CIHR/Canada ; }, mesh = {Adolescent ; Bacteria/*classification/genetics ; Child ; Child, Preschool ; Clostridioides difficile ; Clostridium Infections/*microbiology/*therapy ; Cohort Studies ; DNA, Bacterial ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Humans ; Male ; RNA, Ribosomal, 16S/genetics ; Virulence Factors ; Whole Genome Sequencing ; }, abstract = {BACKGROUNDFecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) in adults and children, but donor stool samples are currently screened for only a limited number of potential pathogens. We sought to determine whether putative procarcinogenic bacteria (enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, and Escherichia coli harboring the colibactin toxin) could be durably transmitted from donors to patients during FMT.METHODSStool samples were collected from 11 pediatric rCDI patients and their respective FMT donors prior to FMT as well as from the patients at 2-10 weeks, 10-20 weeks, and 6 months after FMT. Bacterial virulence factors in stool DNA extracts and stool cultures were measured by quantitative PCR: Bacteroides fragilis toxin (bft), Fusobacterium adhesin A (fadA), and Escherichia coli colibactin (clbB).RESULTSFour of 11 patients demonstrated sustained acquisition of a procarcinogenic bacteria. Whole genome sequencing was performed on colony isolates from one of these donor/recipient pairs and demonstrated that clbB+ E. coli strains present in the recipient after FMT were identical to a strain present in the donor, confirming strain transmission. Conversely, 2 patients exhibited clearance of procarcinogenic bacteria following FMT from a negative donor.CONCLUSIONBoth durable transmission and clearance of procarcinogenic bacteria occurred following FMT, suggesting that additional studies on appropriate screening measures for FMT donors and the long-term consequences and/or benefits of FMT are warranted.FUNDINGCrohn's &amp; Colitis Foundation, the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University School of Medicine, the National Cancer Institute, and the Canadian Institutes of Health Research.}, }
@article {pmid31578199, year = {2019}, author = {Jodal, HC and Helsingen, LM and Anderson, JC and Lytvyn, L and Vandvik, PO and Emilsson, L}, title = {Colorectal cancer screening with faecal testing, sigmoidoscopy or colonoscopy: a systematic review and network meta-analysis.}, journal = {BMJ open}, volume = {9}, number = {10}, pages = {e032773}, pmid = {31578199}, issn = {2044-6055}, mesh = {Adenoma/*diagnosis ; Aged ; Carcinoma/*diagnosis ; Colonoscopy/adverse effects/*methods ; Colorectal Neoplasms/*diagnosis ; Early Detection of Cancer/adverse effects/*methods ; Humans ; Middle Aged ; *Occult Blood ; Sigmoidoscopy/adverse effects ; }, abstract = {OBJECTIVE: Evaluate effectiveness, harms and burdens of faecal blood testing, sigmoidoscopy and colonoscopy screening for colorectal cancer over 15 years.<br><br>DESIGN: We performed an update of a Cochrane systematic review, and performed network meta-analysis comparing randomised trials evaluating colorectal cancer screening with guaiac faecal occult blood test (gFOBT) (annual, biennial), faecal immunochemical test (FIT) (annual, biennial), sigmoidoscopy (once-only) or colonoscopy (once-only) in a healthy population, aged 50-79 years. We conducted subgroup analysis on sex. Follow-up >5 years was required for analysis of colorectal cancer incidence and mortality.<br><br>RESULTS: 12 randomised trials proved eligible. Compared with no-screening, we found high certainty evidence for sigmoidoscopy screening slightly reducing colorectal cancer incidence (relative risk (RR) 0.76; 95% confidence interval (CI 0.70 to 0.83) and mortality (RR 0.74; 95%&#x2009;CI 0.69 to 0.80), while gFOBT screening had little or no difference on colorectal cancer incidence, but slightly reduced colorectal cancer mortality (annual: RR 0.69; 95%&#x2009;CI 0.56 to 0.86, biennial: RR 0.88; 95%&#x2009;CI 0.82 to 0.93). No screening test reduced mortality nor incidence by more than six per 1000 screened over 15 years. Sigmoidoscopy had a greater effect in men, for both colorectal cancer incidence (women: RR 0.86; 95%&#x2009;CI 0.81 to 0.92, men: RR 0.75, 95%&#x2009;CI 0.71 to 0.79), and mortality (women: RR 0.85; 95%&#x2009;CI 0.71 to 0.96, men: RR 0.67; 95%&#x2009;CI 0.61 to 0.75) (moderate certainty).<br><br>CONCLUSIONS: In a 15-year perspective, sigmoidoscopy reduces colorectal cancer incidence, while sigmoidoscopy, annual and biennial gFOBT all reduce colorectal cancer mortality. Sigmoidoscopy may reduce colorectal cancer incidence and mortality more in men than in women.<br><br>PROSPERO REGISTRATION NUMBER: CRD42018093401.}, }
@article {pmid31578196, year = {2019}, author = {Helsingen, LM and Vandvik, PO and Jodal, HC and Agoritsas, T and Lytvyn, L and Anderson, JC and Auer, R and Murphy, SB and Almadi, MA and Corley, DA and Quinlan, C and Fuchs, JM and McKinnon, A and Qaseem, A and Heen, AF and Siemieniuk, RAC and Kalager, M and Usher-Smith, JA and Lansdorp-Vogelaar, I and Bretthauer, M and Guyatt, G}, title = {Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline.}, journal = {BMJ (Clinical research ed.)}, volume = {367}, number = {}, pages = {l5515}, doi = {10.1136/bmj.l5515}, pmid = {31578196}, issn = {1756-1833}, support = {21464/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Aged ; Colonoscopy/standards/*statistics &amp; numerical data ; Colorectal Neoplasms/*diagnosis/epidemiology ; Early Detection of Cancer/methods/*standards/statistics &amp; numerical data ; Female ; Humans ; Incidence ; Male ; Mass Screening/methods/*standards/statistics &amp; numerical data ; Middle Aged ; *Occult Blood ; Outcome and Process Assessment, Health Care/statistics &amp; numerical data ; Patient Acceptance of Health Care/statistics &amp; numerical data ; Sigmoidoscopy/standards/*statistics &amp; numerical data ; Time Factors ; }, abstract = {CLINICAL QUESTION: Recent 15-year updates of sigmoidoscopy screening trials provide new evidence on the effectiveness of colorectal cancer screening. Prompted by the new evidence, we asked: "Does colorectal cancer screening make an important difference to health outcomes in individuals initiating screening at age 50 to 79? And which screening option is best?"<br><br>CURRENT PRACTICE: Numerous guidelines recommend screening, but vary on recommended test, age and screening frequency. This guideline looks at the evidence and makes recommendations on screening for four screening options: faecal immunochemical test (FIT) every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy.<br><br>RECOMMENDATIONS: These recommendations apply to adults aged 50-79 years with no prior screening, no symptoms of colorectal cancer, and a life expectancy of at least 15 years. For individuals with an estimated 15-year colorectal cancer risk below 3%, we suggest no screening (weak recommendation). For individuals with an estimated 15-year risk above 3%, we suggest screening with one of the four screening options: FIT every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy (weak recommendation). With our guidance we publish the linked research, a graphic of the absolute harms and benefits, a clear description of how we reached our value judgments, and linked decision aids.<br><br>A guideline panel including patients, clinicians, content experts and methodologists produced these recommendations using GRADE and in adherence with standards for trustworthy guidelines. A linked systematic review of colorectal cancer screening trials and microsimulation modelling were performed to inform the panel of 15-year screening benefits and harms. The panel also reviewed each screening option's practical issues and burdens. Based on their own experience, the panel estimated the magnitude of benefit typical members of the population would value to opt for screening and used the benefit thresholds to inform their recommendations.<br><br>THE EVIDENCE: Overall there was substantial uncertainty (low certainty evidence) regarding the 15-year benefits, burdens and harms of screening. Best estimates suggested that all four screening options resulted in similar colorectal cancer mortality reductions. FIT every two years may have little or no effect on cancer incidence over 15 years, while FIT every year, sigmoidoscopy, and colonoscopy may reduce cancer incidence, although for FIT the incidence reduction is small compared with sigmoidoscopy and colonoscopy. Screening related serious gastrointestinal and cardiovascular adverse events are rare. The magnitude of the benefits is dependent on the individual risk, while harms and burdens are less strongly associated with cancer risk.<br><br>Based on benefits, harms, and burdens of screening, the panel inferred that most informed individuals with a 15-year risk of colorectal cancer of 3% or higher are likely to choose screening, and most individuals with a risk of below 3% are likely to decline screening. Given varying values and preferences, optimal care will require shared decision making.}, }
@article {pmid31578177, year = {2019}, author = {Buskermolen, M and Cenin, DR and Helsingen, LM and Guyatt, G and Vandvik, PO and Haug, U and Bretthauer, M and Lansdorp-Vogelaar, I}, title = {Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a microsimulation modelling study.}, journal = {BMJ (Clinical research ed.)}, volume = {367}, number = {}, pages = {l5383}, pmid = {31578177}, issn = {1756-1833}, mesh = {Aged ; Colonoscopy/adverse effects/standards/statistics &amp; numerical data ; Colorectal Neoplasms/*diagnosis/epidemiology ; Early Detection of Cancer/methods/*standards/statistics &amp; numerical data ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Mass Screening/methods/*standards/statistics &amp; numerical data ; Middle Aged ; *Models, Statistical ; Norway/epidemiology ; Occult Blood ; Outcome and Process Assessment, Health Care/statistics &amp; numerical data ; Practice Guidelines as Topic ; Sigmoidoscopy/adverse effects/standards/statistics &amp; numerical data ; Survival Analysis ; }, abstract = {OBJECTIVE: To estimate benefits and harms of different colorectal cancer screening strategies, stratified by (baseline) 15-year colorectal cancer risk.<br><br>DESIGN: Microsimulation modelling study using MIcrosimulation SCreening ANalysis-Colon (MISCAN-Colon).<br><br>SETTING: A parallel guideline committee (BMJ Rapid Recommendations) defined the time frame and screening interventions, including selection of outcome measures.<br><br>POPULATION: Norwegian men and women aged 50-79 years with varying 15-year colorectal cancer risk (1-7%).<br><br>COMPARISONS: Four screening strategies were compared with no screening: biennial or annual faecal immunochemical test (FIT) or single sigmoidoscopy or colonoscopy at 100% adherence.<br><br>MAIN OUTCOME MEASURES: Colorectal cancer mortality and incidence, burdens, and harms over 15 years of follow-up. The certainty of the evidence was assessed using the GRADE approach.<br><br>RESULTS: Over 15 years of follow-up, screening individuals aged 50-79 at 3% risk of colorectal cancer with annual FIT or single colonoscopy reduced colorectal cancer mortality by 6 per 1000 individuals. Single sigmoidoscopy and biennial FIT reduced it by 5 per 1000 individuals. Colonoscopy, sigmoidoscopy, and annual FIT reduced colorectal cancer incidence by 10, 8, and 4 per 1000 individuals, respectively. The estimated incidence reduction for biennial FIT was 1 per 1000 individuals. Serious harms were estimated to be between 3 per 1000 (biennial FIT) and 5 per 1000 individuals (colonoscopy); harms increased with older age. The absolute benefits of screening increased with increasing colorectal cancer risk, while harms were less affected by baseline risk. Results were sensitive to the setting defined by the guideline panel. Because of uncertainty associated with modelling assumptions, we applied a GRADE rating of low certainty evidence to all estimates.<br><br>CONCLUSIONS: Over a 15 year period, all screening strategies may reduce colorectal cancer mortality to a similar extent. Colonoscopy and sigmoidoscopy may also reduce colorectal cancer incidence, while FIT shows a smaller incidence reduction. Harms are rare and of similar magnitude for all screening strategies.}, }
@article {pmid31573550, year = {2019}, author = {Dabke, K and Hendrick, G and Devkota, S}, title = {The gut microbiome and metabolic syndrome.}, journal = {The Journal of clinical investigation}, volume = {129}, number = {10}, pages = {4050-4057}, pmid = {31573550}, issn = {1558-8238}, mesh = {Animals ; Diet ; Dyslipidemias/etiology/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions/physiology ; Humans ; Inflammation/etiology/microbiology ; Insulin Resistance ; Metabolic Syndrome/*etiology/metabolism/microbiology ; Models, Biological ; Obesity/etiology/microbiology ; }, abstract = {The metabolic syndrome (MetS) is a constellation of risk factors that, if left untreated, will often progress to greater metabolic defects such as type 2 diabetes and nonalcoholic fatty liver disease. While these risk factors have been established for over 40 years, the definition of MetS warrants reconsideration in light of the substantial data that have emerged from studies of the gut microbiome. In this Review we present the existing recent literature that supports the gut microbiome's potential influence on the various risk factors of MetS. The interplay of the intestinal microbiota with host metabolism has been shown to be mediated by a myriad of factors, including a defective gut barrier, bile acid metabolism, antibiotic use, and the pleiotropic effects of microbially produced metabolites. These data show that events that start in the gut, often in response to external cues such as diet and circadian disruption, have far-reaching effects beyond the gut.}, }
@article {pmid31572686, year = {2019}, author = {Genton, L and Mareschal, J and Charretier, Y and Lazarevic, V and Bindels, LB and Schrenzel, J}, title = {Targeting the Gut Microbiota to Treat Cachexia.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {305}, pmid = {31572686}, issn = {2235-2988}, mesh = {Adult ; Body Mass Index ; Cachexia/*therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Inflammation ; Malnutrition ; Metagenome ; Obesity/therapy ; Probiotics/therapeutic use ; Weight Loss ; }, abstract = {Cachexia occurs in many chronic diseases and is associated with increased morbidity and mortality. It is treated by nutritional support but often with limited effectiveness, leading to the search of other therapeutic strategies. The modulation of gut microbiota, whether through pro-, pre-, syn- or antibiotics or fecal transplantation, is attracting ever-growing interest in the field of obesity, but could also be an interesting and innovative alternative for treating cachexia. This article reviews the evidence linking the features of malnutrition, as defined by the Global Leadership Initiative on Malnutrition [low body mass index (BMI), unintentional body weight loss, low muscle mass, low appetite, and systemic inflammation] and the gut microbiota in human adults with cachexia-associated diseases, and shows the limitations of the present research in that field with suggestions for future directions.}, }
@article {pmid31572201, year = {2019}, author = {Zhou, H and Tai, J and Xu, H and Lu, X and Meng, D}, title = {Xanthoceraside Could Ameliorate Alzheimer's Disease Symptoms of Rats by Affecting the Gut Microbiota Composition and Modulating the Endogenous Metabolite Levels.}, journal = {Frontiers in pharmacology}, volume = {10}, number = {}, pages = {1035}, pmid = {31572201}, issn = {1663-9812}, abstract = {Xanthoceraside (XAN) is a natural-derived compound with anti-Alzheimer activity from the husks of Xanthoceras sorbifolia. Although its therapeutic effect had been confirmed in previous studies, the mechanism was still unclear due to its poor solubility and low permeability. In this study, the pharmacological effect of XAN on Alzheimer's disease (AD) was confirmed by behavior experiments and H&amp;E staining observation. Fecal microbiota transplantation (FMT) experiment also replicated the therapeutic effects, which indicates the potential targets of XAN on gut microbiota. The sequencing of 16S rRNA genes in fecal samples demonstrated that XAN reversed gut microbiota dysbiosis in AD animals. XAN could change the relative abundances of several phyla and genus of bacterial, particularly the ratio of Firmicutes/Bacteroidetes. Among them, Clostridium IV, Desulfovibrio, Corynebacterium, and Enterorhabdus had been reported to be involved in the pathologic developments of AD and other central nervous system disease. In metabolomics study, a series of host endogenous metabolites were detected, including amino acids, lysophosphatidylcholine, dihydrosphingosine, phytosphingosine, inosine, and hypoxanthine, which were all closely associated with the development of AD. Combined with the Spearman's correlation analysis, it was confirmed that the increases of five bacterial strains and decreases of six bacterial strains were closely correlated with the increases of nine host metabolites and the decreases of another five host metabolites. Therefore, XAN can modulate the structure of gut microbiota in AD rats; the changes of gut microbiota were significantly correlated with endogenous metabolites, and symptom of AD was ultimately alleviated. Our findings suggest that XAN may be a potential therapeutic drug for AD, and the gut microbiota may be potential targeting territory of XAN via microbiome-gut-brain pathway.}, }
@article {pmid31571251, year = {2020}, author = {Liu, Y and Chen, K and Li, F and Gu, Z and Liu, Q and He, L and Shao, T and Song, Q and Zhu, F and Zhang, L and Jiang, M and Zhou, Y and Barve, S and Zhang, X and McClain, CJ and Feng, W}, title = {Probiotic Lactobacillus rhamnosus GG Prevents Liver Fibrosis Through Inhibiting Hepatic Bile Acid Synthesis and Enhancing Bile Acid Excretion in Mice.}, journal = {Hepatology (Baltimore, Md.)}, volume = {71}, number = {6}, pages = {2050-2066}, pmid = {31571251}, issn = {1527-3350}, support = {P50AA024337/AA/NIAAA NIH HHS/United States ; P20 GM113226/GM/NIGMS NIH HHS/United States ; U01AA022489-01A1/AA/NIAAA NIH HHS/United States ; R01AA023681/AA/NIAAA NIH HHS/United States ; R21 AA020848/AA/NIAAA NIH HHS/United States ; U01AA021893-01/AA/NIAAA NIH HHS/United States ; 1I01BX002996/VA/VA/United States ; R01AA023190/AA/NIAAA NIH HHS/United States ; R01 AA023190/AA/NIAAA NIH HHS/United States ; R01 AA023681/AA/NIAAA NIH HHS/United States ; U01 AA022489/AA/NIAAA NIH HHS/United States ; R21 AA022416/AA/NIAAA NIH HHS/United States ; I01 BX002996/BX/BLRD VA/United States ; U01 AA021893/AA/NIAAA NIH HHS/United States ; U01 AA021901/AA/NIAAA NIH HHS/United States ; U01AA021901/AA/NIAAA NIH HHS/United States ; P20GM113226/GM/NIGMS NIH HHS/United States ; P50 AA024337/AA/NIAAA NIH HHS/United States ; R21AA020848/AA/NIAAA NIH HHS/United States ; }, mesh = {ATP Binding Cassette Transporter, Subfamily B/genetics ; Animals ; *Bile Acids and Salts/biosynthesis/metabolism ; Chenodeoxycholic Acid/pharmacology ; *Cholestasis/complications/metabolism/therapy ; Cholic Acids/pharmacology ; Fibroblast Growth Factors/*metabolism ; Gastrointestinal Microbiome/drug effects ; Humans ; Intestines/microbiology ; Lacticaseibacillus rhamnosus/*metabolism ; *Liver Cirrhosis/etiology/prevention &amp; control ; Mice ; Mice, Knockout ; Probiotics/pharmacology ; *Receptors, Cytoplasmic and Nuclear/agonists/antagonists &amp; inhibitors/metabolism ; Signal Transduction/drug effects ; ATP-Binding Cassette Sub-Family B Member 4 ; }, abstract = {BACKGROUND AND AIMS: Cholestatic liver disease is characterized by gut dysbiosis and excessive toxic hepatic bile acids (BAs). Modification of gut microbiota and repression of BA synthesis are potential strategies for the treatment of cholestatic liver disease. The purpose of this study was to examine the effects and to understand the mechanisms of the probiotic Lactobacillus rhamnosus GG (LGG) on hepatic BA synthesis, liver injury, and fibrosis in bile duct ligation (BDL) and multidrug resistance protein 2 knockout (Mdr2[-/-]) mice.<br><br>APPROACH AND RESULTS: Global and intestine-specific farnesoid X receptor (FXR) inhibitors were used to dissect the role of FXR. LGG treatment significantly attenuated liver inflammation, injury, and fibrosis with a significant reduction of hepatic BAs in BDL mice. Hepatic concentration of taurine-&#x3b2;-muricholic acid (T-&#x3b2;MCA), an FXR antagonist, was markedly increased in BDL mice and reduced in LGG-treated mice, while chenodeoxycholic acid, an FXR agonist, was decreased in BDL mice and normalized in LGG-treated mice. LGG treatment significantly increased the expression of serum and ileum fibroblast growth factor 15 (FGF-15) and subsequently reduced hepatic cholesterol 7&#x3b1;-hydroxylase and BA synthesis in BDL and Mdr2[-/-] mice. At the molecular level, these changes were reversed by global and intestine-specific FXR inhibitors in BDL mice. In addition, LGG treatment altered gut microbiota, which was associated with increased BA deconjugation and increased fecal and urine BA excretion in both BDL and Mdr2[-/-] mice. In vitro studies showed that LGG suppressed the inhibitory effect of T-&#x3b2;MCA on FXR and FGF-19 expression in Caco-2 cells.<br><br>CONCLUSION: LGG supplementation decreases hepatic BA by increasing intestinal FXR-FGF-15 signaling pathway-mediated suppression of BA de novo synthesis and enhances BA excretion, which prevents excessive BA-induced liver injury and fibrosis in mice.}, }
@article {pmid31570751, year = {2019}, author = {Zhu, L and Zhou, ZB and Shen, D and Chen, AM}, title = {Ipsilateral S2 nerve root transfer to pudendal nerve for restoration of external anal and urethral sphincter function: an anatomical study.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {13993}, pmid = {31570751}, issn = {2045-2322}, mesh = {Adult ; Anal Canal/*innervation/surgery ; Feasibility Studies ; Fecal Incontinence/surgery ; Female ; Humans ; Male ; Pudendal Nerve/anatomy &amp; histology/*surgery ; Spinal Nerve Roots/anatomy &amp; histology/*surgery ; Sural Nerve/anatomy &amp; histology/*transplantation ; Urethra/*innervation/surgery ; Urinary Incontinence/surgery ; }, abstract = {Patients suffer bilateral sacral plexus injuries experience severe problems with incontinence. We performed a cadaveric study to explore the anatomical feasibility of transferring ipsilateral S2 nerve root combined with a sural nerve graft to pudendal nerve for restoration of external anal and urethral sphincter function. The sacral nerve roots and pudendal nerve roots on the right side were exposed in 10 cadavers. The length from S2 nerve root origin to pudendal nerve at inferior border of piriformis was measured. The sural nerve was used as nerve graft. The diameters and nerve cross-sectional areas of S2 nerve root, pudendal nerve and sural nerve were measured and calculated, so as the number of myelinated axons of three nerves on each cadaver specimen. The length from S2 nerve root to pudendal nerve was 10.69 ± 1.67 cm. The cross-sectional areas of the three nerves were 8.57 ± 3.03 mm[2] for S2, 7.02 ± 2.04 mm[2] for pudendal nerve and 6.33 ± 1.61 mm[2] for sural nerve. The pudendal nerve contained approximately the same number of axons (5708 ± 1143) as the sural nerve (5607 ± 1305), which was a bit less than that of the S2 nerve root (6005 ± 1479). The S2 nerve root in combination with a sural nerve graft is surgically feasible to transfer to the pudendal nerve for return of external urethral and anal sphincter function, and may be suitable for clinical application in patients suffering from incontinence following sacral plexus injuries.}, }
@article {pmid31570017, year = {2019}, author = {Elangovan, A and Allegretti, JR and Fischer, M}, title = {Microbiota modulation-based therapy for luminal GI disorders: current applications of probiotics and fecal microbiota transplantation.}, journal = {Expert opinion on biological therapy}, volume = {19}, number = {12}, pages = {1343-1355}, doi = {10.1080/14712598.2019.1673725}, pmid = {31570017}, issn = {1744-7682}, mesh = {Animals ; Dysbiosis/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; Intestinal Diseases/microbiology/*therapy ; Probiotics/adverse effects/*therapeutic use ; }, abstract = {Introduction: Alteration in the intestinal microbiota also termed as intestinal dysbiosis has been demonstrated in numerous gastrointestinal disorders linked to aberrant immune processes, acquisition of pathogenic organisms and often administration of antibiotics. Restoration of microbiota through probiotics and fecal microbiota transplantation (FMT) has gained tremendous popularity among researchers in the prevention and treatment of gastrointestinal diseases.Areas covered: In this review, studies testing the safety and efficacy of probiotics and FMT for the treatment of various infectious and inflammatory luminal gastrointestinal diseases are reviewed. Randomized control studies are given priority while important uncontrolled studies are also highlighted.Expert opinion: Probiotics have demonstrated efficacy in the prevention of antibiotic-associated diarrhea and in the eradication of Helicobacter pylori infection. Their utility in the primary and secondary prevention of Clostridioides difficile infection is debatable. The future of medicine should bring forth a personalized approach to probiotic use. FMT has revolutionized the treatment of recurrent CDI as well as severe and fulminant CDI. At the same time, it has galvanized gut microbiota research in the last decade. While FMT in ulcerative colitis appears promising, further studies on the durability and long-term safety are needed before it can be recommended in clinical practice.}, }
@article {pmid31570003, year = {2019}, author = {Ma, J and Li, J and Qian, M and He, N and Cao, Y and Liu, Y and Wu, K and He, S}, title = {The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {12}, pages = {13560-13571}, doi = {10.1096/fj.201901489R}, pmid = {31570003}, issn = {1530-6860}, mesh = {Animals ; Behavior, Animal ; Depression/etiology/metabolism/*pathology ; *Disease Models, Animal ; Gastrointestinal Microbiome ; Hyperalgesia/etiology/metabolism/*pathology ; Intestinal Mucosa/metabolism/*pathology ; Irritable Bowel Syndrome/chemically induced/metabolism/*physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Corticotropin-Releasing Hormone/genetics/metabolism ; Stress, Physiological ; Trinitrobenzenesulfonic Acid/toxicity ; Visceral Pain/etiology/metabolism/*pathology ; CRF Receptor, Type 1 ; }, abstract = {So far, a comprehensive animal model that can mimic both the central and peripheral pathophysiological changes of irritable bowel syndrome (IBS) is lacking. Here, we developed a novel IBS rat model combining trinitro-benzene-sulfonic acid (TNBS) and chronic unpredictable mild stress (CUMS) (designated as TC-IBS) and compared it with the TNBS-induced and CUMS-induced models. TC-IBS showed a pronounced depression phenotype with increased corticotropin-releasing hormone receptor (CRHR)1 and CRHR2 expression at the frontal cortex and increased serum ACTH concentration. Visceral hypersensitivity (VH), as evidenced by colorectal distention (CRD) test, was highest in TC-IBS, accompanied by increased serum 5-hydroxytryptamine (5-HT) level and colonic 5-HT receptor 3A (5-HT3AR)/5-HT receptor 2B expression, impaired tight junction protein expression including occludin, zonula occludens-1, and phosphorylated myosin light chain. Palonosetron, a second generation of 5-HT3AR antagonist, alleviated VH significantly in TC-IBS. 16S rRNA sequencing showed that TNBS plus CUMS induced a significant disturbance of the gut microbiota. Cytokine profile analysis of TC-IBS model indicated an innate immune activation both in serum and colonic mucosa. Further, fecal microbiota transplantation improved VH and some pathophysiological changes in TC-IBS. In summary, we established a postinflammatory IBS model covering multifactorial pathophysiological changes, which may help to develop therapies that target specific IBS subtype.-Ma, J., Li, J., Qian, M., He, N., Cao, Y., Liu, Y., Wu, K., He, S. The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity.}, }
@article {pmid31566729, year = {2020}, author = {Kusakabe, S and Fukushima, K and Maeda, T and Motooka, D and Nakamura, S and Fujita, J and Yokota, T and Shibayama, H and Oritani, K and Kanakura, Y}, title = {Pre- and post-serial metagenomic analysis of gut microbiota as a prognostic factor in patients undergoing haematopoietic stem cell transplantation.}, journal = {British journal of haematology}, volume = {188}, number = {3}, pages = {438-449}, doi = {10.1111/bjh.16205}, pmid = {31566729}, issn = {1365-2141}, mesh = {Adult ; Allografts ; Autografts ; Bacterial Typing Techniques ; Bifidobacterium/isolation &amp; purification ; Case-Control Studies ; DNA, Bacterial/genetics ; Dysbiosis/complications/microbiology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Hematopoietic Stem Cell Transplantation/adverse effects/*methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Intestines/microbiology ; Male ; Metagenomics/methods ; Middle Aged ; Prognosis ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Survival Analysis ; Transplantation Conditioning/methods ; }, abstract = {The human gut harbours diverse microorganisms, and gut dysbiosis has recently attracted attention because of its possible involvement in various diseases. In particular, the lack of diversity in the gut microbiota has been associated with complications of haematopoietic stem cell transplantation (HSCT), such as infections, acute graft-versus-host disease and relapse of primary disease, which lead to a poor prognosis. However, few studies have serially examined the composition of the intestinal microbiota after HSCT. In this study, we demonstrated, using next-generation sequencing of the bacterial 16S ribosomal RNA gene, combined with uniFrac distance analysis, that the intestinal microbiota of patients undergoing allogeneic HSCT substantially differed from that of healthy controls and recipients of autologous transplants. Faecal samples were obtained daily throughout the clinical course, before and after transplantation. Notably, the proportions of Bifidobacterium and genera categorized as butyrate-producing bacteria were significantly lower in patients with allogeneic HSCT than in healthy controls. Furthermore, among allogeneic transplant recipients, a subgroup with a preserved microbiota composition showed a benign course, whereas patients with a skewed microbiota showed a high frequency of complications and mortality after transplantation. Thus, we conclude that the stability of intestinal microbiota is critically involved in outcomes of HSCT.}, }
@article {pmid31566046, year = {2020}, author = {Kc, D and Sumner, R and Lippmann, S}, title = {Gut microbiota and health.}, journal = {Postgraduate medicine}, volume = {132}, number = {3}, pages = {274}, doi = {10.1080/00325481.2019.1662711}, pmid = {31566046}, issn = {1941-9260}, mesh = {Brain/immunology/metabolism/physiopathology ; Clostridium Infections/microbiology/therapy ; Dysbiosis/immunology/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/microbiology/therapy ; Gastrointestinal Microbiome/immunology/*physiology ; Humans ; Mental Disorders/immunology/microbiology ; Metabolic Syndrome/metabolism/microbiology/therapy ; Prediabetic State/metabolism/microbiology/therapy ; Probiotics/therapeutic use ; }, }
@article {pmid31563878, year = {2019}, author = {Cammarota, G and Ianiro, G and Kelly, CR and Mullish, BH and Allegretti, JR and Kassam, Z and Putignani, L and Fischer, M and Keller, JJ and Costello, SP and Sokol, H and Kump, P and Satokari, R and Kahn, SA and Kao, D and Arkkila, P and Kuijper, EJ and Vehreschild, MJG and Pintus, C and Lopetuso, L and Masucci, L and Scaldaferri, F and Terveer, EM and Nieuwdorp, M and López-Sanromán, A and Kupcinskas, J and Hart, A and Tilg, H and Gasbarrini, A}, title = {International consensus conference on stool banking for faecal microbiota transplantation in clinical practice.}, journal = {Gut}, volume = {68}, number = {12}, pages = {2111-2121}, pmid = {31563878}, issn = {1468-3288}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; *Consensus ; Donor Selection ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; Specimen Handling/methods ; }, abstract = {Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.}, }
@article {pmid31562236, year = {2019}, author = {Lamb, CA and Kennedy, NA and Raine, T and Hendy, PA and Smith, PJ and Limdi, JK and Hayee, B and Lomer, MCE and Parkes, GC and Selinger, C and Barrett, KJ and Davies, RJ and Bennett, C and Gittens, S and Dunlop, MG and Faiz, O and Fraser, A and Garrick, V and Johnston, PD and Parkes, M and Sanderson, J and Terry, H and ,  and Gaya, DR and Iqbal, TH and Taylor, SA and Smith, M and Brookes, M and Hansen, R and Hawthorne, AB}, title = {British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults.}, journal = {Gut}, volume = {68}, number = {Suppl 3}, pages = {s1-s106}, pmid = {31562236}, issn = {1468-3288}, support = {12076/CRUK_/Cancer Research UK/United Kingdom ; G0902022/MRC_/Medical Research Council/United Kingdom ; MC_U127527198/MRC_/Medical Research Council/United Kingdom ; MR/M00533X/1/MRC_/Medical Research Council/United Kingdom ; 18927/CRUK_/Cancer Research UK/United Kingdom ; EME/13/179/01/DH_/Department of Health/United Kingdom ; MC_UU_00007/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_U127527198/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; *Consensus ; Conservative Treatment/*standards ; *Disease Management ; *Gastroenterology ; Humans ; Inflammatory Bowel Diseases/*therapy ; Practice Guidelines as Topic/*standards ; *Societies, Medical ; United Kingdom ; }, abstract = {Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.}, }
@article {pmid31560944, year = {2019}, author = {Gong, Y and Dong, R and Gao, X and Li, J and Jiang, L and Zheng, J and Cui, S and Ying, M and Yang, B and Cao, J and He, Q}, title = {Neohesperidin prevents colorectal tumorigenesis by altering the gut microbiota.}, journal = {Pharmacological research}, volume = {148}, number = {}, pages = {104460}, doi = {10.1016/j.phrs.2019.104460}, pmid = {31560944}, issn = {1096-1186}, mesh = {Animals ; Bacteroidetes/drug effects ; Carcinogenesis/*drug effects ; Colorectal Neoplasms/*prevention &amp; control ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Firmicutes/drug effects ; Gastrointestinal Microbiome/*drug effects/genetics ; Hesperidin/*analogs &amp; derivatives/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microbiota/drug effects/genetics ; Proteobacteria/drug effects ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Neohesperidin (NHP), derived from citrus fruits, has attracted considerable interest due to its preventative and therapeutic effects on numerous diseases. However, little progress has been made in determining the exact function of NHP on tumorigenesis. In the current study, we found that NHP inhibited colorectal tumorigenesis in the APC [min/+] transgenic mouse model, as well as induced apoptosis and blocked angiogenesis in vivo. Our in-cell study suggested that this tumorigenic preventative effect of NHP is not due to the direct impact on tumor cells. Intriguingly, by utilizing 16 s rRNA gene-based microbiota sequencing, the relative abundance of Bacteroidetes was decreased, while Firmicutes and Proteobacteria were increased in the presence of NHP. Additionally, the fecal microbiota transplantation experiment further revealed that feeding with fecal of NHP-treated mice induced considerable inhibition of tumorigenesis, which indicates that the alteration of gut microbiota is responsible for NHP-mediated prevention of colorectal tumorigenesis. Thus, our study not only suggests the efficacy of NHP as a potent natural product for preventing colorectal cancer but also proposes a compelling model to connect the gut microbiota to the preventative effect of NHP on tumorigenesis.}, }
@article {pmid31560873, year = {2019}, author = {Roman, P and Cardona, D and Sempere, L and Carvajal, F}, title = {Microbiota and organophosphates.}, journal = {Neurotoxicology}, volume = {75}, number = {}, pages = {200-208}, doi = {10.1016/j.neuro.2019.09.013}, pmid = {31560873}, issn = {1872-9711}, mesh = {Animals ; Gastrointestinal Microbiome/physiology ; Humans ; Organophosphate Poisoning/metabolism/*microbiology/prevention &amp; control ; Organophosphates/toxicity ; }, abstract = {Organophosphates (OPs) are important toxic compounds commonly used for a variety of purposes in agriculture, industry and household settings. Consumption of these compounds affects several central nervous system functions. Some of the most recognised consequences of organophosphate pesticide exposure in humans include neonatal developmental abnormalities, endocrine disruption, neurodegeneration, neuroinflammation and cancer. In addition, neurobehavioral and emotional deficits following OP exposure have been reported. It would be of great value to discover a therapeutic strategy which produces a protective effect against these neurotoxic compounds. Moreover, a growing body of preclinical data suggests that the microbiota may affect metabolism and neurotoxic outcomes through exposure to OPs. The human gut is colonised by a broad variety of microorganisms. This huge number of bacteria and other microorganisms which survive by colonising the gastrointestinal tract is defined as "gut microbiota". The gut microbiome plays a profound role in metabolic processing, energy production, immune and cognitive development and homeostasis. The effects are not only localized in the gut, but also influence many other organs, such as the brain through the microbiome-gut-brain axis. Therefore, given the gut microbiota's key role in host homeostasis, this microbiota may be altered or modified temporarily by factors such as antibiotics, diet and toxins such as pesticides. The aim of this review is to examine scientific articles concerning the impact of microbiota in OP toxicity. Studies focussed on the possible contribution the microbiota has on variable host pharmacokinetic responses such as absorption and biotransformation of xenobiotics will be evaluated. Microbiome manipulation by antibiotic or probiotic administration and faecal transplantation are experimental approaches recently proposed as treatments for several diseases. Finally, microbiota manipulation as a possible therapeutic strategy in order to reduce OP toxicity will be discussed.}, }
@article {pmid31560744, year = {2020}, author = {Chande, N and Costello, SP and Limketkai, BN and Parker, CE and Nguyen, TM and Macdonald, JK and Feagan, BG}, title = {Alternative and Complementary Approaches for the Treatment of Inflammatory Bowel Disease: Evidence From Cochrane Reviews.}, journal = {Inflammatory bowel diseases}, volume = {26}, number = {6}, pages = {843-851}, doi = {10.1093/ibd/izz223}, pmid = {31560744}, issn = {1536-4844}, mesh = {*Cannabis ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*therapy ; *Nutrition Therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, }
@article {pmid31560732, year = {2019}, author = {Smith, AD and Foss, ED and Zhang, I and Hastie, JL and Giordano, NP and Gasparyan, L and VinhNguyen, LP and Schubert, AM and Prasad, D and McMichael, HL and Sun, J and Beger, RD and Simonyan, V and Cowley, SC and Carlson, PE}, title = {Microbiota of MR1 deficient mice confer resistance against Clostridium difficile infection.}, journal = {PloS one}, volume = {14}, number = {9}, pages = {e0223025}, pmid = {31560732}, issn = {1932-6203}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage/adverse effects ; Cefoperazone/administration &amp; dosage/adverse effects ; Clostridium Infections/etiology/*immunology/microbiology/therapy ; Disease Models, Animal ; Disease Resistance/*genetics/immunology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects/*immunology ; Histocompatibility Antigens Class I/*genetics/immunology ; Humans ; Intestinal Mucosa/cytology/immunology/microbiology ; Mice ; Mice, Knockout ; Minor Histocompatibility Antigens/*genetics/immunology ; Mucosal-Associated Invariant T Cells/immunology ; Specific Pathogen-Free Organisms ; }, abstract = {Clostridium difficile (Cd) infection (CDI) typically occurs after antibiotic usage perturbs the gut microbiota. Mucosa-associated invariant T cells (MAIT) are found in the gut and their development is dependent on Major histocompatibility complex-related protein 1 (MR1) and the host microbiome. Here we were interested in determining whether the absence of MR1 impacts resistance to CDI. To this end, wild-type (WT) and MR1-/- mice were treated with antibiotics and then infected with Cd spores. Surprisingly, MR1-/- mice exhibited resistance to Cd colonization. 16S rRNA gene sequencing of feces revealed inherent differences in microbial composition. This colonization resistance was transferred from MR1-/- to WT mice via fecal microbiota transplantation, suggesting that MR1-dependent factors influence the microbiota, leading to CDI susceptibility.}, }
@article {pmid31560045, year = {2020}, author = {Abu-Sbeih, H and Wang, Y}, title = {Management Considerations for Immune Checkpoint Inhibitor-Induced Enterocolitis Based on Management of Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {26}, number = {5}, pages = {662-668}, doi = {10.1093/ibd/izz212}, pmid = {31560045}, issn = {1536-4844}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Diarrhea/chemically induced/immunology/*therapy ; Disease Management ; Enterocolitis/chemically induced/immunology/*therapy ; Fecal Microbiota Transplantation ; Humans ; Immune Checkpoint Inhibitors/*adverse effects ; Infliximab/therapeutic use ; }, abstract = {BACKGROUND: Immune checkpoint inhibitor therapy has significantly improved the outcomes of various advanced malignancies that were deemed unruly prior to its invention. Immune-mediated diarrhea and enterocolitis are among the most frequently encountered adverse events of immune checkpoint inhibitor therapy. Given the increasing use of these therapies in the treatment of an ever-growing number of malignancies, providing appropriate treatment for such adverse effects has become crucial.<br><br>METHODS: In this review, we summarize the current body of evidence concerning the management of immune-mediated diarrhea and enterocolitis. Additionally, management of immune-mediated diarrhea and enterocolitis is likened to that of inflammatory bowel disease, given the resemblance between both entities in pathogenesis and clinical features. Reviewing the literature raised several points regarding this devastating toxicity that still need further investigation by future efforts.<br><br>RESULTS: Endoscopic and histologic evaluation is pivotal in the assessment of immune-mediated diarrhea and enterocolitis and provides vital information regarding the severity of the disease to guide treatment. Corticosteroids are the main therapy for immune-mediated diarrhea and enterocolitis, with infliximab and vedolizumab as second-line agents. Recently, fecal microbiota transplantation has emerged as a treatment option for immune-mediated diarrhea and enterocolitis that is refractory to corticosteroids. Restarting immune checkpoint inhibitor therapy after resolution of immune-mediated diarrhea and enterocolitis carries a risk of recurrence that is mostly controllable with current immune-suppressive treatment.<br><br>CONCLUSIONS: Lastly, we propose a management algorithm for immune-mediated diarrhea and enterocolitis. Prospective research, preferably as collaborative efforts from oncology and gastroenterology specialists, is needed to refine the management of immune-mediated diarrhea and enterocolitis.}, }
@article {pmid31559564, year = {2019}, author = {Li, J and Wei, H}, title = {Establishment of an efficient germ-free animal system to support functional microbiome research.}, journal = {Science China. Life sciences}, volume = {62}, number = {10}, pages = {1400-1403}, doi = {10.1007/s11427-019-9832-9}, pmid = {31559564}, issn = {1869-1889}, mesh = {Animals ; Anti-Bacterial Agents/metabolism ; Bacteria/metabolism ; Fecal Microbiota Transplantation ; Food/adverse effects ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; *Microbiota ; *Models, Animal ; Stomach Diseases/metabolism ; }, }
@article {pmid31559298, year = {2019}, author = {Hu, Y and Xiao, HY and He, C and Lv, NH and Zhu, L}, title = {Fecal microbiota transplantation as an effective initial therapy for pancreatitis complicated with severe Clostridium difficile infection: A case report.}, journal = {World journal of clinical cases}, volume = {7}, number = {17}, pages = {2597-2604}, pmid = {31559298}, issn = {2307-8960}, abstract = {BACKGROUND: Moderately severe acute pancreatitis (MSAP) is a critical form of acute pancreatitis that is related with high morbidity and mortality. Severe Clostridium difficile infection (sCDI) is a serious and rare nosocomial diarrheal complication, especially in MSAP patients. Fecal microbiota transplantation (FMT) is a highly effective treatment for refractory and recurrent CDI (rCDI). However, knowledge regarding the initial use of FMT in patients suffering from sCDI is limited.<br><br>CASE SUMMARY: Here, we report an MSAP patient complicated with sCDI who was treated by FMT as a first-line therapy. The patient was a 51-year-old man who suffered from diarrhea in his course of acute pancreatitis. An enzyme immunoassay was performed to detect toxins, and the result was positive for toxin-producing C. difficile and toxin B and negative for C. difficile ribotype 027. The colonoscopy revealed pseudomembranous colitis. Due to these findings, sCDI was our primary consideration. Because the patient provided informed consent for FMT treatment, we initially treated the patient by FMT rather than metronidazole. Diarrhea resolved within 5 d after FMT. The patient remained asymptomatic, and the follow-up colonoscopy performed 40 d after discharge showed a complete recovery. Our case is the first reported in China.<br><br>CONCLUSION: This case explores the possibilities of initially using FMT to treat severe CDI. Moreover, FMT may become a critical component of the treatment for severe CDI in MSAP patients.}, }
@article {pmid31559265, year = {2019}, author = {Grosen, AK and Povlsen, JV and Lemming, LE and Jørgensen, SMD and Dahlerup, JF and Hvas, CL}, title = {Faecal Microbiota Transplantation Eradicated Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae from a Renal Transplant Recipient with Recurrent Urinary Tract Infections.}, journal = {Case reports in nephrology and dialysis}, volume = {9}, number = {2}, pages = {102-107}, pmid = {31559265}, issn = {2296-9705}, abstract = {Renal transplant recipients (RTRs) are highly susceptible to infections, and antimicrobial resistance is an increasing problem with limited treatment options. Faecal microbiota transplantation (FMT) is effective for recurrent Clostridium difficile infection and may be used for patients with intestinal carriage of multidrug-resistant (MDR) microorganisms. We present a RTR who suffered from recurrent urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase-producing (ESBL+) Klebsiella pneumoniae. Blood and urinary isolates revealed the same antibiotic susceptibility pattern, and whole-genome sequencing confirmed identical isolates in blood and urine. Despite several treatments with meropenem, the patient experienced recurrent infections that caused hospitalisation. ESBL+ K. pneumoniae was isolated in faeces. In an attempt to decolonise the gut, FMT was performed. A few days after nasojejunal infusion of donor faeces, the patient experienced a single relapse of UTI. During the subsequent 12 months, no further episodes of UTI occurred. Absence of ESBL+ K. pneumoniae in urine and faeces was demonstrated during follow-up. We conclude that FMT may be an effective treatment in RTRs with recurrent UTIs caused by intestinal colonisation with MDR organisms.}, }
@article {pmid31559142, year = {2019}, author = {Zheng, P and Li, Y and Wu, J and Zhang, H and Huang, Y and Tan, X and Pan, J and Duan, J and Liang, W and Yin, B and Deng, F and Perry, SW and Wong, ML and Licinio, J and Wei, H and Yu, G and Xie, P}, title = {Perturbed Microbial Ecology in Myasthenia Gravis: Evidence from the Gut Microbiome and Fecal Metabolome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {6}, number = {18}, pages = {1901441}, pmid = {31559142}, issn = {2198-3844}, abstract = {Myasthenia gravis (MG) is a devastating acquired autoimmune disease. Emerging evidence indicates that the gut microbiome plays a key role in maintaining immune system homeostasis. This work reports that MG is characterized by decreased α-phylogenetic diversity, and significantly disturbed gut microbiome and fecal metabolome. The altered gut microbial composition is associated with fecal metabolome changes, with 38.75% of altered bacterial operational taxonomic units showing significant correlations with a range of metabolite biomarkers. Some microbes are particularly linked with MG severity. Moreover, a combination of microbial makers and their correlated metabolites enable discriminating MG from healthy controls (HCs) with 100% accuracy. To investigate whether disturbed gut mcirobiome might contribute to the onset of MG, germ-free (GF) mice are initially colonized with MG microbiota (MMb) or healthy microbiota (HMb), and then immunized in a classic mouse model of MG. The MMb mice demonstrate substantially impaired locomotion ability compared with the HMb mice. This effect could be reversed by cocolonizing GF mice with both MMb and HMb. The MMb mice also exhibit similar disturbances of fecal metabolic pathways as found in MG. Together these data demonstrate disturbances in microbiome composition and activity that are likely to be relevant to the pathogenesis of MG.}, }
@article {pmid31558007, year = {2019}, author = {Son, DH and Park, WJ and Lee, YJ}, title = {Recent Advances in Anti-Aging Medicine.}, journal = {Korean journal of family medicine}, volume = {40}, number = {5}, pages = {289-296}, pmid = {31558007}, issn = {2005-6443}, abstract = {A rapidly aging population in Korea has led to increased attention in the field of anti-aging medicine. The purpose of anti-aging medicine is to slow, stop, or reverse the aging process and its associated effects, such as disability and frailty. Anti-aging medicine is emerging as a growing industry, but many supplements or protocols are available that do not have scientific evidence to support their claims. In this review, the mechanisms of action and the clinical implications of anti-aging interventions were examined and explained. Calorie restriction mimetics define compounds that imitate the outcome of calorie restriction, including an activator of AMP protein kinase (metformin), inhibitor of growth hormone/insulin-like growth factor-1 axis (pegvisomant), inhibitor of mammalian target of rapamycin (rapamycin), and activator of the sirtuin pathway (resveratrol). Hormonal replacement has also been widely used in the elderly population to improve their quality of life. Manipulating healthy gut microbiota through prebiotic/probiotics or fecal microbiota transplantation has significant potential in anti-aging medicine. Vitamin D is expected to be a primary anti-aging medicine in the near future due to its numerous positive effects in the elderly population.}, }
@article {pmid31557953, year = {2019}, author = {Zhang, Z and Mocanu, V and Cai, C and Dang, J and Slater, L and Deehan, EC and Walter, J and Madsen, KL}, title = {Impact of Fecal Microbiota Transplantation on Obesity and Metabolic Syndrome-A Systematic Review.}, journal = {Nutrients}, volume = {11}, number = {10}, pages = {}, pmid = {31557953}, issn = {2072-6643}, support = {./CAPMC/CIHR/Canada ; }, mesh = {*Fecal Microbiota Transplantation ; Humans ; Metabolic Syndrome/*therapy ; Obesity/*therapy ; }, abstract = {Fecal microbiota transplantation (FMT) is a gut microbial-modulation strategy that has been investigated for the treatment of a variety of human diseases, including obesity-associated metabolic disorders. This study appraises current literature and provides an overview of the effectiveness and limitations of FMT as a potential therapeutic strategy for obesity and metabolic syndrome (MS). Five electronic databases and two gray literature sources were searched up to 10 December 2018. All interventional and observational studies that contained information on the relevant population (adult patients with obesity and MS), intervention (receiving allogeneic FMT) and outcomes (metabolic parameters) were eligible. From 1096 unique citations, three randomized placebo-controlled studies (76 patients with obesity and MS, body mass index = 34.8 ± 4.1 kg/m[2], fasting plasma glucose = 5.8 ± 0.7 mmol/L) were included for review. Studies reported mixed results with regards to improvement in metabolic parameters. Two studies reported improved peripheral insulin sensitivity (rate of glucose disappearance, RD) at 6 weeks in patients receiving donor FMT versus patients receiving the placebo control. In addition, one study observed lower HbA1c levels in FMT patients at 6 weeks. No differences in fasting plasma glucose, hepatic insulin sensitivity, body mass index (BMI), or cholesterol markers were observed between two groups across all included studies. While promising, the influence of FMT on long-term clinical endpoints needs to be further explored. Future studies are also required to better understand the mechanisms through which changes in gut microbial ecology and engraftment of microbiota affect metabolic outcomes for patients with obesity and MS. In addition, further research is needed to better define the optimal fecal microbial preparation, dosing, and method of delivery.}, }
@article {pmid31555606, year = {2019}, author = {DeLong, K and Bensouda, S and Zulfiqar, F and Zierden, HC and Hoang, TM and Abraham, AG and Coleman, JS and Cone, RA and Gravitt, PE and Hendrix, CW and Fuchs, EJ and Gaydos, CA and Weld, ED and Ensign, LM}, title = {Conceptual Design of a Universal Donor Screening Approach for Vaginal Microbiota Transplant.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {306}, pmid = {31555606}, issn = {2235-2988}, support = {R01 HD092013/HD/NICHD NIH HHS/United States ; UL1 TR001079/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Donor Selection/*methods ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Lactobacillus/genetics ; Microbiota/genetics/*physiology ; Sexually Transmitted Diseases ; Surveys and Questionnaires ; Urinary Tract Infections/microbiology ; Vagina/*microbiology ; Vaginosis, Bacterial/microbiology/*therapy ; Young Adult ; }, abstract = {The success of fecal microbiota transplant (FMT) in treating recurrent Clostridioides difficile infection has led to growing excitement about the potential of using transplanted human material as a therapy for a wide range of diseases and conditions related to microbial dysbiosis. We anticipate that the next frontier of microbiota transplantation will be vaginal microbiota transplant (VMT). The composition of the vaginal microbiota has broad impact on sexual and reproductive health. The vaginal microbiota in the "optimal" state are one of the simplest communities, dominated by one of only a few species of Lactobacillus. Diversity in the microbiota and the concomitant depletion of lactobacilli, a condition referred to as bacterial vaginosis (BV), is associated with a wide range of deleterious effects, including increased risk of acquiring sexually transmitted infections and increased likelihood of having a preterm birth. However, we have very few treatment options available, and none of them curative or restorative, for "resetting" the vaginal microbiota to a more protective state. In order to test the hypothesis that VMT may be a more effective treatment option, we must first determine how to screen donors to find those with minimal risk of pathogen transmission and "optimal" vaginal microbiota for transplant. Here, we describe a universal donor screening approach that was implemented in a small pilot study of 20 women. We further characterized key physicochemical properties of donor cervicovaginal secretions (CVS) and the corresponding composition of the vaginal microbiota to delineate criteria for inclusion/exclusion. We anticipate that the framework described here will help accelerate clinical studies of VMT.}, }
@article {pmid31555343, year = {2019}, author = {Pezo, RC and Wong, M and Martin, A}, title = {Impact of the gut microbiota on immune checkpoint inhibitor-associated toxicities.}, journal = {Therapeutic advances in gastroenterology}, volume = {12}, number = {}, pages = {1756284819870911}, pmid = {31555343}, issn = {1756-283X}, abstract = {Immune checkpoint inhibitors (ICIs) have transformed the treatment of patients with advanced cancers. However, the majority of patients do not respond or develop early progressive disease. A substantial number also develop immune-mediated toxicities that may lead to early treatment discontinuation. Gastrointestinal toxicities in the form of diarrhea and colitis are common and may resemble that observed in patients with inflammatory bowel disease (IBD). Alterations in the gut microbiota are thought to play an important role in mediating the intestinal inflammation that is associated with immune-mediated colitis. In this review, the authors' objective is to provide an overview of the gastrointestinal and hepatic toxicities that can be seen with ICIs and discuss the interactions between gut microbiota and the immune response. The authors also highlight the potential role for fecal microbial transfer (FMT) as an approach to improve therapeutic efficacy and decrease toxicity.}, }
@article {pmid31554900, year = {2019}, author = {Zachariassen, LF and Hansen, AK and Krych, L and Nielsen, DS and Holm, TL and Tougaard, P and Hansen, CHF}, title = {Cesarean section increases sensitivity to oxazolone-induced colitis in C57BL/6 mice.}, journal = {Mucosal immunology}, volume = {12}, number = {6}, pages = {1348-1357}, pmid = {31554900}, issn = {1935-3456}, mesh = {Animals ; Cesarean Section/*adverse effects ; Colitis/*chemically induced/immunology/metabolism/microbiology ; Colon/*immunology/metabolism/microbiology/pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Inflammation Mediators/metabolism ; Intestinal Mucosa/*immunology/metabolism/microbiology/pathology ; Mice, Inbred C57BL ; *Oxazolone ; Peroxidase/metabolism ; Pregnancy ; Severity of Illness Index ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Children born by cesarean section (CS) have an increased risk of developing inflammatory bowel disease (IBD), possibly due to skewed microbial colonization during birth and consequently impaired bacterial stimulation of the developing immune system. The aim of this study was to investigate the association between CS and experimental colitis in a murine model of IBD. It was hypothesized that CS aggravates colonic inflammation due to a change in gut microbiota (GM) composition. C57BL/6 mice, delivered by CS or vaginal delivery (VD), were intra-rectally challenged with oxazolone at 8 weeks of age and monitored for colitis symptoms. The results showed that CS delivered mice experienced an increased body weight loss and colon weight, together with higher colonic concentrations of TNF-α and MPO compared with VD mice. Increased infiltration of inflammatory cells was present in CS delivered mice, as well as a downregulation in expression of the gut integrity genes occludin and tight junction protein 1 indicative of an impaired barrier function. The GM from CS delivered mice without colitis partly contributed to the increase in colitis symptoms when inoculated into germ-free recipient mice. In conclusion, CS increased sensitivity to oxazolone induced colitis in mice.}, }
@article {pmid31554603, year = {2019}, author = {Arita, S and Inagaki-Ohara, K}, title = {High-fat-diet-induced modulations of leptin signaling and gastric microbiota drive precancerous lesions in the stomach.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {67-68}, number = {}, pages = {110556}, doi = {10.1016/j.nut.2019.110556}, pmid = {31554603}, issn = {1873-1244}, mesh = {Animals ; Diet, High-Fat/*adverse effects ; Dysbiosis/etiology/metabolism/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/*physiology ; Leptin/*metabolism ; Male ; Metaplasia/etiology/metabolism/microbiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Mutant Strains ; Mutation ; Precancerous Conditions/*etiology/metabolism/microbiology ; Receptors, Leptin/deficiency/genetics/*metabolism ; Signal Transduction ; Stomach/pathology ; Stomach Neoplasms/*etiology/metabolism/microbiology ; }, abstract = {OBJECTIVES: Obesity is a risk factor for malignancy in various tissues, and has been associated with gut microbiota alterations. However, the link between obesity-associated microbiota and gastric pathogenesis has not been clarified. We demonstrated that high-fat-diet (HFD) feeding causes intestinal metaplasia, which are precancerous lesions of the stomach, with augmented gastric leptin signaling. The aim of this study was to investigate the precise role of leptin signaling in the altered microbiota composition and pathogenesis in the stomach during diet-induced obesity.<br><br>METHODS: Male C57 BL/6 J, leptin receptor (Lepr)-mutated db/db, and gastrointestinal epithelium-specific Lepr conditional knockout (T3 b-Lepr cKO) mice were fed a HFD or control diet. Gastrointestinal microbiota was analyzed by 16 S rRNA gene sequences and quantitative polymerase chain reaction. Transplantation of gastric microbiota of HFD-fed mice was performed to evaluate metaplasia onset in recipient mice.<br><br>RESULTS: One week of HFD caused severe microbial dysbiosis in the stomach. The microbiota changes were accompanied by increased gastric leptin, leading to the consequent development of intestinal metaplasia. Transplantation of gastric microbiota from HFD-fed mice induced intestinal metaplasia in recipient mice; however, only a limited effect on pathogenesis was noted. HFD-fed db/db mice did not show a decrease in microbial abundance. Moreover, T3 b-Lepr cKO mice failed spontaneous obesity, and suppressed decreased abundance of gastric microbiota and occurrence of intestinal metaplasia during HFD feeding similar to db/db mice.<br><br>CONCLUSIONS: Gastric leptin signaling modulates the gastric microbiota community and regulates the pathogenesis in the gastric mucosa.}, }
@article {pmid31551944, year = {2019}, author = {Kim, J and Lee, H and An, J and Song, Y and Lee, CK and Kim, K and Kong, H}, title = {Alterations in Gut Microbiota by Statin Therapy and Possible Intermediate Effects on Hyperglycemia and Hyperlipidemia.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1947}, pmid = {31551944}, issn = {1664-302X}, abstract = {Dysbiosis of the gut microbiota is a contributing factor for obesity-related metabolic diseases such as hyperglycemia and hyperlipidemia. Pharmacotherapy for metabolic diseases involves the modulation of gut microbiota, which is suggested to be a potential therapeutic target. In this study, the modulation of gut microbiota by statins (cholesterol-lowering drugs: atorvastatin and rosuvastatin) was investigated in an aged mouse model of high-fat diet-induced obesity, and the association between gut microbiota and immune responses was described. Atorvastatin and rosuvastatin significantly increased the abundance of the genera Bacteroides, Butyricimonas, and Mucispirillum. Moreover, the abundance of these genera was correlated with the inflammatory response, including levels of IL-1β and TGFβ1 in the ileum. In addition, oral fecal microbiota transplantation with fecal material collected from rosuvastatin-treated mouse groups improved hyperglycemia. From these results, the effect of statins on metabolic improvements could be explained by altered gut microbiota. Our findings suggest that the modulation of gut microbiota by statins has an important role in the therapeutic actions of these drugs.}, }
@article {pmid31550826, year = {2019}, author = {Li, N and Tian, HL and Chen, QY and Yang, B and Ma, CL and Lin, ZL and Zhang, XY and Zhao, D and Huang, ZX and Jiang, J and Qin, HL}, title = {[Efficacy analysis of fecal microbiota transplantation in the treatment of 2010 patients with intestinal disorders].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {22}, number = {9}, pages = {861-868}, doi = {10.3760/cma.j.issn.1671-0274.2019.09.011}, pmid = {31550826}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; 04.99.18001//Special Fund for the Construction of the Clinical Center of Tenth People's Hospital of Tongji University/ ; }, mesh = {Adolescent ; Adult ; Aged ; Bacteria/genetics ; China ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; *Intestinal Diseases/therapy ; Male ; Middle Aged ; RNA, Ribosomal, 16S ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for intestinal disorders. Methods: A retrospectively descriptive cohort study was carried out. Clinical data of 2010 patients who underwent FMT and received follow-up for more than 3 months from May 2014 to November 2018 were collected, including 1,206 cases from Tongji University Shanghai Tenth People's Hospital and 804 cases from Nanjing Eastern Military General Hospital. Of the 2,010 patients, 797 were male and 1,213 were female, with a mean age of (49.4±16.5) years old. Inclusion criteria were those with indications for FMT and voluntary treatment of FMT. Pregnant or lactating women, patients with end-stage disease, cases who were participating or participated in other clinical trials within 3 months, and patients with previous bowel history of pathogen infection, oral antibiotics or proton pump inhibitors (PPI) for the recent2 weeks, and those at immunosuppressive state were excluded. Informed consent was obtained from the enrolled patients and their families. There were 1,356 cases of constipation, 175 cases of inflammatory bowel disease, 148 cases of chronic diarrhea, 127 cases of radiation enteritis, 119 cases of irritable bowel syndrome, and 85 cases of autism (complicating with intestinal disorders). FMT donor requirements: (1) 18 to 30 years old non-relatives, non-pregnant healthy adults with healthy lifestyle and good eating habits as volunteers to participate in fecal donation; (2) no administration of antibiotics within 3 months; (3) no chronic diseases such as constipation, irritable bowel syndrome, inflammatory bowel disease, etc., no autoimmune disease, not in immunosuppressive state, no history of malignant disease; (4) negative pathogen examination of infectious diseases (hepatitis B virus, hepatitis C virus, syphilis, HIV, etc.); (5) negative fecal examination (C.difficile, dysentery bacillus, Shigella, Campylobacter, parasites, etc.). The donor requirements after enrollment: (1) physical examination was reviewed once every two months, and the result still met the above requirements; (2) 16S rRNA sequencing was performed for every fecal donation in order to ensure that the composition and diversity of the fecal flora was stable and reliable. The preparation of the stool suspension referred to the Amsterdam criteria and the preparation process was less than 1 hour. The preparation of the FMT capsule was processed by pre-freezing the stool suspension after the preparation of the above suspension, and the frozen sample was transferred into a freeze dryer for freezing. The dried and lyophilized powder was encapsulated in capsules, and the capsule shell was made of acid-resistant hypromellose capsule (No.0) and pediatric-specific capsule (No.3), sealed and packaged in a-20℃ refrigerator. Three ways of accepting FMT treatment pathways included 6-day transplantation after the placement of the nasointestinal tube, 6-day oral FMT capsule transplantation and one-time transplantation through colonoscopy. Intestinal preparation (nasointestinal tube feeding of polyethylene glycol until watery stool) was carried out before transplantation. Other treatments were stopped during treatment and follow-up, and any medication was not recommended when necessary. Results: Of the 2010 patients, 1,497 cases received nasointestinal tube transplantation (nasointestinal tube group), 452 cases oral capsule transplantation (oral capsule group) and 61 cases colonoscopy (colonoscopy group). At 3 time points of 3, 12, and 36 months after FMT, the clinical cure rates and the clinical improvement rates were 41.3% (560/1 356), 35.2% (320/909), 31.4% (69/220), and 29.0% (393/1 356), 27.8% (253/909), 29.1% (64/220), respectively in constipation patients; 33.1% (58/175), 29.9% (35/117), 24.5% (12/49), and 31.4% (55/175), 27.4% (32/117), 57.1% (28/49), respectively in inflammatory bowel disease patients; 87.8% (130/148), 81.8% (81/99), 78.3% (36/46), and 8.1% (12/148), 7.1% (7/99), 4.3% (2/46), respectively in chronic diarrhea patients; 61.4% (78/127), 56.5% (48/85), 47.6% (20/42), and 21.2% (27/127), 15.3% (13/85), 14.3% (6/42), respectively in radiation enteritis patients; 53.8% (64/119), 45.0% (36/80), 6/15, and 21.0% (25/119), 26.2% (21/80), 4/15, respectively in irritable bowel syndrome patients; 23.5% (20/85), 22.8% (13/57), 20.0%(5/25), and 55.3% (47/85), 49.1% (28/57), 40.0% (10/25), respectively in autism patients. Meanwhile the clinical cure rates and the clinical improvement rates at 3, 12, and 36 months were 47.7% (714/1 497), 42.8% (425/994), 39.1% (128/327), and 29.1% (436/1 497), 27.0% (268/994), 28.1% (92/327), respectively in the nasointestinal tube group; 38.7% (175/452), 30.2% (91/301), 33.3% (16/48), and 24.3% (110/452), 26.2% (79/301), 25.0% (12/48), respectively in the oral capsule group; 34.4% (21/61), 32.7% (17/52), 18.2% (4/22), and 21.3% (13/61), 13.5% (7/52), 45.5% (10/22), respectively in colonoscopy group. No serious adverse events occurred during treatment and follow-up period. The adverse event of nasointestinal tube group presented higher ratio of discomfort in respiratorytract accounting for 13.1% (196/1497); the oral capsule group had a higher proportion of nausea and vomiting when swallowing capsules accounting for 7.1% (32/452); the colonoscopy group was mainly diarrhea, accounting for 37.7% (23/61). The above symptoms disappeared after the nasointestinal tube was removed, or after treatment ended, or within 1 to 3 days after hospitalization. Conclusion: FMT is a safe and effective method for the treatment of intestinal dysfunction.}, }
@article {pmid31550348, year = {2019}, author = {Cotter, JM and Nicholson, MR and Kociolek, LK}, title = {An Infectious Diseases Perspective on Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {8}, number = {6}, pages = {580-584}, pmid = {31550348}, issn = {2048-7207}, support = {K23 AI123525/AI/NIAID NIH HHS/United States ; KL2 TR002245/TR/NCATS NIH HHS/United States ; }, mesh = {Clostridioides difficile ; Clostridium Infections/*etiology/*therapy ; Communicable Diseases/*etiology ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Humans ; Immunocompromised Host ; Patient Safety ; Prospective Studies ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is efficacious for treatment of recurrent Clostridioides difficile infections (rCDIs). Pediatric experience with FMT for rCDIs is increasing, particularly at large centers. While retrospective studies suggest that FMT is generally safe in the short term, particularly in immunocompetent patients and with rigorous donor screening, additional large prospective studies are needed. This particularly includes those at high risk for infectious complications, such as immunocompromised hosts. Further, long-term implications of altering the intestinal microbiome with FMT are not well understood. The role of FMT in children, particularly in high-risk patients, will require continual reexamination with future availability of pediatric safety and efficacy data. This review summarizes key points for infectious diseases physicians to consider when evaluating a child for FMT.}, }
@article {pmid31550030, year = {2019}, author = {Slomski, A}, title = {Fecal Transplant Doesn't Improve Symptoms of IBS.}, journal = {JAMA}, volume = {322}, number = {12}, pages = {1134}, doi = {10.1001/jama.2019.14756}, pmid = {31550030}, issn = {1538-3598}, }
@article {pmid31545802, year = {2019}, author = {Guirro, M and Costa, A and Gual-Grau, A and Herrero, P and Torrell, H and Canela, N and Arola, L}, title = {Effects from diet-induced gut microbiota dysbiosis and obesity can be ameliorated by fecal microbiota transplantation: A multiomics approach.}, journal = {PloS one}, volume = {14}, number = {9}, pages = {e0218143}, pmid = {31545802}, issn = {1932-6203}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Biodiversity ; Body Weight ; *Diet ; Disease Models, Animal ; *Dysbiosis ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Male ; Metagenome ; Metagenomics ; Obesity/*physiopathology/therapy ; Rats ; }, abstract = {Obesity and its comorbidities are currently considered an epidemic, and the involved pathophysiology is well studied. Hypercaloric diets are tightly related to the obesity etiology and also cause alterations in gut microbiota functionality. Diet and antibiotics are known to play crucial roles in changes in the microbiota ecosystem and the disruption of its balance; therefore, the manipulation of gut microbiota may represent an accurate strategy to understand its relationship with obesity caused by diet. Fecal microbiota transplantation, during which fecal microbiota from a healthy donor is transplanted to an obese subject, has aroused interest as an effective approach for the treatment of obesity. To determine its success, a multiomics approach was used that combined metagenomics and metaproteomics to study microbiota composition and function. To do this, a study was performed in rats that evaluated the effect of a hypercaloric diet on the gut microbiota, and this was combined with antibiotic treatment to deplete the microbiota before fecal microbiota transplantation to verify its effects on gut microbiota-host homeostasis. Our results showed that a high-fat diet induces changes in microbiota biodiversity and alters its function in the host. Moreover, we found that antibiotics depleted the microbiota enough to reduce its bacterial content. Finally, we assessed the use of fecal microbiota transplantation as a complementary obesity therapy, and we found that it reversed the effects of antibiotics and reestablished the microbiota balance, which restored normal functioning and alleviated microbiota disruption. This new approach could be implemented to support the dietary and healthy habits recommended as a first option to maintain the homeostasis of the microbiota.}, }
@article {pmid31544324, year = {2019}, author = {Lee, JR and Huang, J and Magruder, M and Zhang, LT and Gong, C and Sholi, AN and Albakry, S and Edusei, E and Muthukumar, T and Lubetzky, M and Dadhania, DM and Taur, Y and Pamer, EG and Suthanthiran, M}, title = {Butyrate-producing gut bacteria and viral infections in kidney transplant recipients: A pilot study.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {21}, number = {6}, pages = {e13180}, pmid = {31544324}, issn = {1399-3062}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R37 AI 051652//National Institute of Allergy and Infectious Diseases/ ; K23 AI124464/AI/NIAID NIH HHS/United States ; K23 AI 124464//National Institute of Allergy and Infectious Diseases/ ; R37 AI051652/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/adverse effects ; Antibiotic Prophylaxis/adverse effects ; Bacteria/drug effects/immunology/*isolation &amp; purification/metabolism ; Bacterial Infections/immunology/prevention &amp; control ; Butyrates/metabolism ; DNA, Bacterial/isolation &amp; purification ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/drug effects/*physiology ; Graft Rejection/immunology/prevention &amp; control ; Humans ; Immunosuppressive Agents/adverse effects ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; Respiratory Tract Infections/*epidemiology/immunology/virology ; Virus Diseases/*epidemiology/immunology/virology ; }, abstract = {BACKGROUND: The gut microbiome is being associated increasingly with development of infections besides Clostridium difficile infection. A recent study found an association between butyrate-producing gut (BPG) bacteria and less frequent development of lower respiratory viral infections in allogeneic hematopoietic stem cell transplant recipients (Haak et al, Blood 131(26): 2978, 2018). In this investigation, we examine the relationship between the abundance of BPG bacteria and the development of viral infections in a cohort of kidney transplant recipients.<br><br>METHODS: We recruited 168 kidney transplant recipients who provided 510 fecal specimens in the first 3&#xa0;months after transplantation and profiled the gut microbiota using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We classified the kidney transplant recipients into higher BPG Bacteria Group and lower BPG Bacteria Group using the same criteria of 1% relative gut abundance of BPG bacteria as the Haak et al study.<br><br>RESULTS: Administration of antibiotics against anaerobes was associated with a significant decrease in the relative gut abundance of BPG bacteria. The higher BPG Bacteria Group was associated with less development of respiratory viral infections (Hazard Ratio [HR]: 0.28, P&#xa0;=&#xa0;.01) but not with less development of CMV viremia (HR: 0.38, P&#xa0;=&#xa0;.13) or BK viremia (HR: 1.02, P&#xa0;=&#xa0;.98) at 2&#xa0;years post transplantation.<br><br>CONCLUSION: Our pilot investigation supports future validation of the relationship between high relative gut abundance of BPG bacteria and decreased risk for development of respiratory viral infections.}, }
@article {pmid31543403, year = {2019}, author = {Yuan, J and Chen, C and Cui, J and Lu, J and Yan, C and Wei, X and Zhao, X and Li, N and Li, S and Xue, G and Cheng, W and Li, B and Li, H and Lin, W and Tian, C and Zhao, J and Han, J and An, D and Zhang, Q and Wei, H and Zheng, M and Ma, X and Li, W and Chen, X and Zhang, Z and Zeng, H and Ying, S and Wu, J and Yang, R and Liu, D}, title = {Fatty Liver Disease Caused by High-Alcohol-Producing Klebsiella pneumoniae.}, journal = {Cell metabolism}, volume = {30}, number = {4}, pages = {675-688.e7}, doi = {10.1016/j.cmet.2019.08.018}, pmid = {31543403}, issn = {1932-7420}, mesh = {Animals ; Ethanol/*metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Hep G2 Cells ; Humans ; Klebsiella pneumoniae/*metabolism/pathogenicity ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/*microbiology ; }, abstract = {The underlying etiology of nonalcoholic fatty liver disease (NAFLD) is believed to be quite varied. Changes in the gut microbiota have been investigated and are believed to contribute to at least some cases of the disease, though a causal relationship remains unclear. Here, we show that high-alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) is associated with up to 60% of individuals with NAFLD in a Chinese cohort. Transfer of clinical isolates of HiAlc Kpn by oral gavage into mice induced NAFLD. Likewise, fecal microbiota transplant (FMT) into mice using a HiAlc-Kpn-strain-containing microbiota isolated from an individual with NASH induced NAFLD. However, selective elimination of the HiAlc Kpn strain before FMT prevented NAFLD in the recipient mice. These results suggest that at least in some cases of NAFLD an alteration in the gut microbiome drives the condition due to excess endogenous alcohol production.}, }
@article {pmid31542262, year = {2019}, author = {Yitbarek, A and Astill, J and Hodgins, DC and Parkinson, J and Nagy, &#xc9; and Sharif, S}, title = {Commensal gut microbiota can modulate adaptive immune responses in chickens vaccinated with whole inactivated avian influenza virus subtype H9N2.}, journal = {Vaccine}, volume = {37}, number = {44}, pages = {6640-6647}, doi = {10.1016/j.vaccine.2019.09.046}, pmid = {31542262}, issn = {1873-2518}, mesh = {*Adaptive Immunity/drug effects ; Animals ; Anti-Bacterial Agents/pharmacology ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Chickens/*immunology ; Gastrointestinal Microbiome/drug effects/*immunology ; Hemagglutination Inhibition Tests ; Host-Pathogen Interactions/immunology ; Immunoglobulin A/immunology ; Immunoglobulin G/immunology ; *Immunomodulation/drug effects ; Influenza A Virus, H9N2 Subtype/*immunology ; Influenza Vaccines/*immunology ; Interferon-gamma/biosynthesis ; Neutralization Tests ; Poultry Diseases/*prevention &amp; control ; Probiotics ; Vaccines, Inactivated/*immunology ; }, abstract = {Variations in the composition of commensal gut microbiota have been reported to be major contributors to differences in responses to vaccination among individuals. In chickens, there is limited information on the role of gut microbiota in responses to vaccination. The current study studied the role of gut microbiota in cell- and antibody-mediated immune responses to vaccination with a whole inactivated avian influenza virus, subtype H9N2. A total of 166 one-day-old specific pathogen free layer chickens (SPF) were randomly assigned to treatments, where a combination of antibiotic depletion, and probiotics (a combination of five Lactobacillus species) or fecal microbial transplant (FMT) reconstitution were used to study the dynamics of cell- and antibody-mediated immune responses to primary and secondary vaccinations at days 15 and 29 of age, respectively. Overall, at days 7 and 14 post primary vaccination (p.p.v.), administration of probiotics to non-depleted chickens resulted in significantly higher mean hemagglutination (HI) titre compared to antibiotic treated chickens. Furthermore, at day 21 p.p.v., chickens treated with probiotics or FMT post-antibiotic treatment showed a significantly higher mean HI titre compared to non-depleted chickens treated with probiotics. At day 7 p.p.v., a significantly higher virus specific IgM and IgG titres were observed in non-depleted chickens administered with probiotics compared to antibiotic depleted chickens, and a significantly higher IgG titre was observed in chickens treated with FMT following antibiotic treatment compared to only antibiotic treatment. Analysis of interferon gamma expression in splenocytes to assess cell-mediated immune responses showed a significantly lower expression in antibiotic-treated chickens compared to non-depleted chickens and FMT reconstituted chickens. Taken together, the current study suggests that shifts in the composition of gut microbiota of chickens may result in changes in cell- and antibody-mediated immune responses to vaccination against influenza viruses. Further studies will be needed to highlight the mechanisms involved in this modulation.}, }
@article {pmid31541527, year = {2019}, author = {Poloni, JAT and Zanotelli, ML and Pedroso, AS and Trein, MR and Tasca, T}, title = {Strongyloides stercoralis larvae or egg: Which came first?.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {21}, number = {6}, pages = {e13177}, doi = {10.1111/tid.13177}, pmid = {31541527}, issn = {1399-3062}, mesh = {Animals ; Antiparasitic Agents/therapeutic use ; Carcinoma, Hepatocellular/surgery ; Feces/parasitology ; Graft Rejection/immunology/prevention &amp; control ; Humans ; *Immunocompromised Host ; Immunosuppressive Agents/adverse effects ; Ivermectin/therapeutic use ; Larva ; Liver Cirrhosis/surgery ; Liver Neoplasms/surgery ; Liver Transplantation/*adverse effects ; Male ; Middle Aged ; Ovum ; Strongyloides stercoralis/*isolation &amp; purification ; Strongyloidiasis/*diagnosis/drug therapy/immunology/microbiology ; Superinfection/*diagnosis/drug therapy/immunology/microbiology ; Treatment Outcome ; }, abstract = {Strongyloides stercoralis (SS) hyperinfection is a well-documented condition. However, SS eggs in stool samples are not commonly observed during routine analysis. Here, we report a case on SS hyperinfection where both larvae and eggs were observed in the stool sample of an immunossupressed liver allograft transplanted patient.}, }
@article {pmid31540133, year = {2019}, author = {Meroni, M and Longo, M and Dongiovanni, P}, title = {Alcohol or Gut Microbiota: Who Is the Guilty?.}, journal = {International journal of molecular sciences}, volume = {20}, number = {18}, pages = {}, pmid = {31540133}, issn = {1422-0067}, mesh = {Alcoholism/genetics/immunology/*microbiology/physiopathology ; Animals ; Anti-Bacterial Agents/adverse effects ; Bile Acids and Salts/metabolism ; Diet ; Dietary Supplements/microbiology ; Dysbiosis/immunology/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Hepatocytes/metabolism ; Humans ; Intestines/microbiology ; Liver/metabolism/physiopathology ; Liver Diseases, Alcoholic/immunology/metabolism/*microbiology/physiopathology ; }, abstract = {Alcoholic liver disease (ALD), a disorder caused by excessive alcohol intake represents a global health care burden. ALD encompasses a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The susceptibility of alcoholic patients to develop ALD is highly variable and its progression to more advanced stages is strongly influenced by several hits (i.e., amount and duration of alcohol abuse). Among them, the intestinal microbiota and its metabolites have been recently identified as paramount in ALD pathophysiology. Ethanol abuse triggers qualitative and quantitative modifications in intestinal flora taxonomic composition, mucosal inflammation, and intestinal barrier derangement. Intestinal hypermeability results in the translocation of viable pathogenic bacteria, Gram-negative microbial products, and pro-inflammatory luminal metabolites into the bloodstream, further corroborating the alcohol-induced liver damage. Thus, the premise of this review is to discuss the beneficial effect of gut microbiota modulation as a novel therapeutic approach in ALD management.}, }
@article {pmid31534208, year = {2019}, author = {Giles, EM and D'Adamo, GL and Forster, SC}, title = {The future of faecal transplants.}, journal = {Nature reviews. Microbiology}, volume = {17}, number = {12}, pages = {719}, pmid = {31534208}, issn = {1740-1534}, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/methods/*standards/*trends ; Humans ; Patient Safety/*standards ; }, }
@article {pmid31533218, year = {2019}, author = {Villéger, R and Lopès, A and Carrier, G and Veziant, J and Billard, E and Barnich, N and Gagnière, J and Vazeille, E and Bonnet, M}, title = {Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?.}, journal = {International journal of molecular sciences}, volume = {20}, number = {18}, pages = {}, pmid = {31533218}, issn = {1422-0067}, support = {1071//the Minist&#xe8;re de la Recherche et de la Technologie, Inserm and Universit&#xe9; Clermont-Auvergne/ ; USC2018//INRA/ ; 63//la ligue contre le cancer/ ; 16-IDEX-0001-CAP 20-25//French government IDEX-ISITE initiative/ ; 2015/622//CIFRE grant/ ; 2016//CPER EPICURE/ ; }, mesh = {Animals ; Combined Modality Therapy ; *Gastrointestinal Microbiome/drug effects/radiation effects ; Humans ; Neoplasms/diagnosis/*therapy ; Prognosis ; Treatment Outcome ; }, abstract = {Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.}, }
@article {pmid31530527, year = {2019}, author = {Bahmani, S and Azarpira, N and Moazamian, E}, title = {Anti-colon cancer activity of Bifidobacterium metabolites on colon cancer cell line SW742.}, journal = {The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology}, volume = {30}, number = {9}, pages = {835-842}, pmid = {31530527}, issn = {2148-5607}, mesh = {Bifidobacterium/isolation &amp; purification/*metabolism ; Colonic Neoplasms/*prevention &amp; control ; Humans ; *Probiotics ; Time Factors ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND/AIMS: Bacteria species, which are used as probiotics, are lactic acid bacteria. The majority of them are under the genera Bifidobacterium and Lactobacillus. The aim of the present study was to isolate and identify Bifidobacterium and to evaluate the effects of their 24 h and 120 h cell-free supernatants (CFS) from both cultures on colon cancer cell line.<br><br>MATERIALS AND METHODS: In the present study, 84 samples of dairy products, infant feces, and probiotic capsule were collected, and Bifidobacterium was isolated. Gram stain, biochemical tests, and molecular identification were done for the isolation and identification of Bifidobacterium. Cytotoxicity effects of CFS derived from both cultures of isolated Bifidobacterium were assessed on colon cancer cell lines.<br><br>RESULTS: In the present study, 17 isolates of Bifidobacterium were identified. The results show that Bifidobacterium was most frequently associated with infant feces and dairy products, whereas the lowest rate was associated with local milk. After the effects of CFS on colon cancer cell line, two isolates were identified from infant feces and probiotic capsule; they had the highest ability in inhibiting the growth of cancer cells. Bifidobacterium bifidum was effective in combating cancer cells and was associated with a substantial improvement in gastrointestinal cancer.<br><br>CONCLUSION: The study has shown that the regular ingested probiotics could prevent the development of colorectal cancer. During the present study, the produced CFS could inhibit the growth of colon cancer cells. In conclusion, probiotics have good potential to be introduced as a new approach to colon cancer treatment.}, }
@article {pmid31529413, year = {2020}, author = {Castaño-Rodríguez, N and Paramsothy, S and Kaakoush, NO}, title = {Promise of Fecal Microbiota Transplantation Therapy in Pouchitis.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {4}, pages = {1107-1110}, pmid = {31529413}, issn = {1573-2568}, mesh = {*Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Pilot Projects ; *Pouchitis ; }, }
@article {pmid31528199, year = {2019}, author = {Du, H and Kuang, TT and Qiu, S and Xu, T and Gang Huan, CL and Fan, G and Zhang, Y}, title = {Fecal medicines used in traditional medical system of China: a systematic review of their names, original species, traditional uses, and modern investigations.}, journal = {Chinese medicine}, volume = {14}, number = {}, pages = {31}, pmid = {31528199}, issn = {1749-8546}, abstract = {In China, the medical use of fecal matter (fresh fecal suspension or dry feces) can be dated back to the fourth century, approximately 1700 years ago. In long-term clinical practice, Chinese doctors have accumulated unique and invaluable medical experience in the use of fecal materials. In view of their good curative effect and medicinal potential, fecal medicines should be paid much attention. This study aimed to provide the first comprehensive data compilation of fecal medicines used in various Chinese traditional medical systems by bibliographic investigation of 31 medicine monographs and standards. A total of 54 fecal medicines were found to be used in 14 traditional Chinese medical systems. Their names, original species, medicinal forms, and traditional uses were described in detail. These fecal medicines were commonly used to treat gastrointestinal, nervous system, skin, and gynecological diseases. Commonly used fecal medicines include Wu-Ling-Zhi, Jiu-Fen and Hei-Bing-Pian. The information summarized in this study can provide a good reference for the development and utilization of fecal medicines. Further studies are necessary to prove their medicinal value, identify their active ingredients, and elucidate their mechanisms of action so that more people can accept these special medicines.}, }
@article {pmid31527823, year = {2019}, author = {Ilett, EE and Jørgensen, M and Noguera-Julian, M and Daugaard, G and Murray, DD and Helleberg, M and Paredes, R and Lundgren, J and Sengeløv, H and MacPherson, C}, title = {Gut microbiome comparability of fresh-frozen versus stabilized-frozen samples from hospitalized patients using 16S rRNA gene and shotgun metagenomic sequencing.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {13351}, pmid = {31527823}, issn = {2045-2322}, mesh = {Bacteria/*classification/genetics/*isolation &amp; purification ; Cryopreservation/*methods ; DNA, Bacterial/genetics ; Feces/*microbiology ; Freezing ; Gastrointestinal Microbiome/*genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenome/genetics ; Metagenomics/methods ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; Specimen Handling ; }, abstract = {Collection of faecal samples for microbiome analysis in acutely sick patients is logistically difficult, particularly if immediate freezing is required (i.e. fresh-frozen, or FF sampling). Previous studies in healthy/non-hospitalized volunteers have shown that chemical stabilization (i.e. stabilized-frozen, or SF sampling) allows room-temperature storage with comparable results to FF samples. To test this in a hospital setting we compared FF and SF approaches across 17 patients undergoing haematopoietic stem cell transplantation (HSCT) using both 16S rRNA gene and shotgun metagenomic sequencing. A paired (same stool specimen) comparison of FF and SF samples was made, with an overall comparable level in relative taxonomic abundances between the two sampling techniques. Though shotgun metagenomic sequencing found significant differences for certain bacterial genera (P < 0.001), these were considered minor methodological effects. Within-sample diversity of either method was not significantly different (Shannon diversity P16SrRNA = 0.68 and Pshotgun = 0.89) and we could not reject the null hypothesis that between-sample variation in FF and SF were equivalent (P16SrRNA = 0.98 and Pshotgun = 1.0). This indicates that SF samples can be used to reliably study the microbiome in acutely sick patient populations, thus creating and enabling further outcomes-based metagenomic studies on similarly valuable cohorts.}, }
@article {pmid31527292, year = {2019}, author = {Janket, SJ and Ackerson, LK and Diamandis, EP}, title = {Gut microbiotas and immune checkpoint inhibitor therapy response: a causal or coincidental relationship?.}, journal = {Clinical chemistry and laboratory medicine}, volume = {58}, number = {1}, pages = {18-24}, doi = {10.1515/cclm-2019-0605}, pmid = {31527292}, issn = {1437-4331}, mesh = {Animals ; Gastrointestinal Microbiome/*drug effects ; Humans ; Immunity/*drug effects ; *Molecular Targeted Therapy ; }, abstract = {As the largest immune organ, human gut microbiome could influence the efficacy of immune checkpoint inhibitor therapy (ICI). However, identifying contributory microbes from over 35,000 species is virtually impossible and the identified microbes are not consistent among studies. The reason for the disparity may be that the microbes found in feces are markers of other factors that link immune response and microbiotas. Notably, gut microbiome is influenced by stool consistency, diet and other lifestyle factors. Therefore, the ICI and microbiotas relationship must be adjusted for potential confounders and analyzed longitudinally. Moreover, a recent study where 11 low-abundance commensal bacteria induced interferon-γ-producing CD8 T cells, challenges the validity of the abundance-oriented microbiotas investigations. This study also confirmed the hierarchy in immunogenic roles among microbiotas. Fecal transplantation trials in germ-free mice provided "the proof of principle" that germ-free mice reproduce the donor's microbiome and corresponding ICI efficacy. However, species-specific biological differences prevent direct extrapolation between the results in murine and human models. Fecal transplantation or supplementation with microbes found in ICI responders requires caution due to potential adverse events.}, }
@article {pmid31527206, year = {2019}, author = {Reynolds, SB and Maghavani, DP and Hashmi, H}, title = {Acquired factor X deficiency in a patient with multiple myeloma: a rare case highlighting the significance of comprehensive evaluation and the need for antimyeloma therapy for bleeding diathesis.}, journal = {BMJ case reports}, volume = {12}, number = {9}, pages = {}, pmid = {31527206}, issn = {1757-790X}, mesh = {Anti-Inflammatory Agents/therapeutic use ; Antineoplastic Agents/therapeutic use ; Bortezomib/therapeutic use ; Combined Modality Therapy ; Dexamethasone/therapeutic use ; Diagnosis, Differential ; Factor X Deficiency/*etiology/*therapy ; Humans ; Immunologic Factors/therapeutic use ; Lenalidomide/therapeutic use ; Male ; Melena ; Middle Aged ; Multiple Myeloma/*complications/*therapy ; Stem Cell Transplantation ; }, abstract = {Factor X deficiency is a rare bleeding disorder that can be associated with life-threatening bleeding events. Factor X deficiency can either be inherited or acquired. Acquired cases of factor X deficiency can be seen in patients with plasma cell dyscrasias as well as amyloidosis. Coagulopathy, with clinically relevant bleeding events, although rare, is not an unusual phenomenon for patients with systemic amyloidosis. However, clinically relevant bleeding in patients with symptomatic multiple myeloma, without associated amyloidosis, has not been reported in literature before. We present a rare case of multiple myeloma without concomitant amyloidosis that presented with life-threatening bleeding from acquired deficiency of factor X and responded remarkably to treatment for underlying multiple myeloma. This case not only highlights the diagnostic workup required in patients with factor X deficiency but also provides the principles of management of acquired coagulopathy in plasma cell dyscrasias.}, }
@article {pmid31526871, year = {2019}, author = {Wu, R and Mei, X and Ye, Y and Xue, T and Wang, J and Sun, W and Lin, C and Xue, R and Zhang, J and Xu, D}, title = {Zn(II)-curcumin solid dispersion impairs hepatocellular carcinoma growth and enhances chemotherapy by modulating gut microbiota-mediated zinc homeostasis.}, journal = {Pharmacological research}, volume = {150}, number = {}, pages = {104454}, doi = {10.1016/j.phrs.2019.104454}, pmid = {31526871}, issn = {1096-1186}, mesh = {Animals ; Antineoplastic Agents/chemistry/pharmacology/*therapeutic use ; Carcinoma, Hepatocellular/blood/*drug therapy/microbiology/pathology ; Cell Line, Tumor ; Cell Survival/drug effects ; Curcumin/chemistry/pharmacology/*therapeutic use ; Doxorubicin/chemistry/pharmacology/*therapeutic use ; Drug Synergism ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Homeostasis/drug effects ; Humans ; Ileum/drug effects/pathology ; Liver/drug effects/pathology ; Liver Neoplasms/blood/*drug therapy/microbiology/pathology ; Male ; Mice, Inbred BALB C ; RNA, Ribosomal, 16S/analysis ; Rats, Sprague-Dawley ; Zinc/blood/chemistry/pharmacology/*therapeutic use ; }, abstract = {Zinc(II) complexes of curcumin display moderate cytotoxicity towards cancer cells at low micromolar concentrations. However, the clinical use of zinc(II) complexes is hampered by hydrolytic insolubility and poor bioavailability and their anticancer mechanisms remain unclear. Here, we investigated the efficacy and mechanism of action of a polyvinylpyrrolidone (PVP-k30)-based solid dispersion of Zn(II)-curcumin (ZnCM-SD) against hepatocellular carcinoma (HCC) in vitro and in vivo. In vitro assays revealed ZnCM-SD not only reduced the viability of HepG2 cells and SK-HEP1 cells in a dose-dependent manner, but also potently and synergistically enhanced cell growth inhibition and cell death in response to doxorubicin by regulating cellular zinc homeostasis. ZnCM-SD was internalized into the cells via non-specific endocytosis and degraded to release curcumin and Zn[2+] ions within cells. The anticancer effects also occur in vivo in animals following the oral administration of ZnCM-SD, without significantly affecting the weight of the animals. Interestingly, ZnCM-SD did not reduce tumor growth or affect zinc homeostasis in HepG2-bearing mice after gut microbiome depletion. Moreover, administration of ZnCM-SD alone or in combination with doxorubicin significantly attenuated gut dysbiosis and zinc dyshomeostasis in a rat HCC model. Notably, fecal microbiota transplantation revealed the ability of ZnCM-SD to regulate zinc homeostasis and act as a chemosensitizer for doxorubicin were dependent on the gut microbiota. The crucial role of the gut microbiota in the chemosensitizing ability of ZnCM-SD was confirmed by broad-spectrum antibiotic treatment. Collectively, ZnCM-SD could represent a simple, well-tolerated, safe, effective therapy and function as a novel chemosensitizing agent for cancer.}, }
@article {pmid31526431, year = {2019}, author = {Lavazza, A and Sironi, VA}, title = {Are we Ready for a "Microbiome-Guided Behaviour" Approach?.}, journal = {Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees}, volume = {28}, number = {4}, pages = {708-724}, doi = {10.1017/S0963180119000653}, pmid = {31526431}, issn = {1469-2147}, mesh = {Behavior/*physiology ; *Brain ; Fecal Microbiota Transplantation ; Humans ; Metaphor ; *Microbiota ; }, abstract = {The microbiome is proving to be increasingly important for human brain functioning. A series of recent studies have shown that the microbiome influences the central nervous system in various ways, and consequently acts on the psychological well-being of the individual by mediating, among others, the reactions of stress and anxiety. From a specifically neuroethical point of view, according to some scholars, the particular composition of the microbiome-qua microbial community-can have consequences on the traditional idea of human individuality. Another neuroethical aspect concerns the reception of this new knowledge in relation to clinical applications. In fact, attention to the balance of the microbiome-which includes eating behavior, the use of psychobiotics and, in the treatment of certain diseases, the use of fecal microbiota transplantation-may be limited or even prevented by a biased negative attitude. This attitude derives from a prejudice related to everything that has to do with the organic processing of food and, in general, with the human stomach and intestine: the latter have traditionally been regarded as low, dirty, contaminated and opposed to what belongs to the mind and the brain. This biased attitude can lead one to fail to adequately consider the new anthropological conceptions related to the microbiome, resulting in a state of health, both physical and psychological, inferior to what one might have by paying the right attention to the knowledge available today. Shifting from the ubiquitous high-low metaphor (which is synonymous with superior-inferior) to an inside-outside metaphor can thus be a neuroethical strategy to achieve a new and unbiased reception of the discoveries related to the microbiome.}, }
@article {pmid31526274, year = {2019}, author = {Schwartz, DJ and Rebeck, ON and Dantas, G}, title = {Complex interactions between the microbiome and cancer immune therapy.}, journal = {Critical reviews in clinical laboratory sciences}, volume = {56}, number = {8}, pages = {567-585}, pmid = {31526274}, issn = {1549-781X}, support = {R01 AT009741/AT/NCCIH NIH HHS/United States ; R25 GM103757/GM/NIGMS NIH HHS/United States ; R01 AI123394/AI/NIAID NIH HHS/United States ; R01 HD092414/HD/NICHD NIH HHS/United States ; U01 AI123394/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Clinical Trials as Topic ; Fecal Microbiota Transplantation ; Humans ; *Immunotherapy ; *Microbiota ; Neoplasms/immunology/*microbiology/*therapy ; Treatment Outcome ; }, abstract = {Immuno-oncology has rapidly grown in the last thirty years, and immunotherapeutic agents are now approved to treat many disparate cancers. Immune checkpoint inhibitors (ICIs) are employed to augment cytotoxic anti-cancer activity by inhibiting negative regulatory elements of the immune system. Modulating the immune system to target neoplasms has improved survivability of numerous cancers in many individuals, but forecasting outcomes post therapy is difficult due to insufficient predictive biomarkers. Recently, the tumor and gastrointestinal microbiome and immune milieu have been investigated as predictors and influencers of cancer immune therapy. In this review, we discuss: (1) ways to measure the microbiome including relevant bioinformatic analyses, (2) recent developments in animal studies and human clinical trials utilizing gut microbial composition and function as biomarkers of cancer immune therapy response and toxicity, and (3) using prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplant (FMT) to modulate immune therapy. We discuss the respective benefits of 16S ribosomal RNA (rRNA) gene and shotgun metagenomic sequencing including important considerations in obtaining samples and in designing and interpreting human and animal microbiome studies. We then focus on studies discussing the differences in response to ICIs in relation to the microbiome and inflammatory mediators. ICIs cause colitis in up to 25% of individuals, and colitis is often refractory to common immunosuppressive medications. Researchers have measured microbiota composition prior to ICI therapy and correlated baseline microbiota composition with efficacy and colitis. Certain bacterial taxa that appear to enhance therapeutic benefit are also implicated in increased susceptibility to colitis, alluding to a delicate balance between pro-inflammatory tumor killing and anti-inflammatory protection from colitis. Pre-clinical and clinical models have trialed probiotic administration, e.g. Bifidobacterium spp. or FMT, to treat colitis when immune suppressive agents fail. We are excited about the future of modulating the microbiome to predict and influence cancer outcomes. Furthermore, novel therapies employed for other illnesses including bacteriophage and genetically-engineered microbes can be adapted in the future to promote increased advancements in cancer treatment and side effect management.}, }
@article {pmid31525370, year = {2019}, author = {Faivre, B and Bellenger, J and Rieu, A and Guivier, E and Galan, M and Ollivier, A and Poloni, L and Sorci, G}, title = {Disentangling the effect of host genetics and gut microbiota on resistance to an intestinal parasite.}, journal = {International journal for parasitology}, volume = {49}, number = {11}, pages = {873-883}, doi = {10.1016/j.ijpara.2019.06.001}, pmid = {31525370}, issn = {1879-0135}, mesh = {Animals ; Disease Models, Animal ; *Disease Resistance ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Genetic Background ; *Host-Parasite Interactions ; Mice, Inbred Strains ; Nematospiroides dubius/*immunology ; Strongylida Infections/*immunology ; }, abstract = {Resistance to infection is a multifactorial trait, and recent work has suggested that the gut microbiota can also contribute to resistance. Here, we performed a fecal microbiota transplant to disentangle the contribution of the gut microbiota and host genetics as drivers of resistance to the intestinal nematode Heligmosomoides polygyrus. We transplanted the microbiota of a strain of mice (SJL), resistant to H. polygyrus, into a susceptible strain (CBA) and vice-versa. We predicted that if the microbiota shapes resistance to H. polygyrus, the FMT should reverse the pattern of resistance between the two host strains. The two host strains had different microbiota diversities and compositions before the start of the experiment, and the FMT altered the microbiota of recipient mice. One mouse strain (SJL) was more resistant to colonization by the heterologous microbiota, and it maintained its resistance profile to H. polygyrus (lower parasite burden) independently of the FMT. On the contrary, CBA mice harbored parasites with lower fecundity during the early stage of the infection, and had an up-regulated expression of the cytokine IL-4 (a marker of H. polygyrus resistance) after receiving the heterologous microbiota. Therefore, while host genetics remains the main factor shaping the pattern of resistance to H. polygyrus, the composition of the gut microbiota also seems to play a strain-specific role.}, }
@article {pmid31524867, year = {2019}, author = {Daharsh, L and Zhang, J and Ramer-Tait, A and Li, Q}, title = {A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {150}, pages = {}, pmid = {31524867}, issn = {1940-087X}, support = {R21 AI122377/AI/NIAID NIH HHS/United States ; P20 GM103427/GM/NIGMS NIH HHS/United States ; R01 AI124804/AI/NIAID NIH HHS/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; R21 AI143405/AI/NIAID NIH HHS/United States ; R01 AI111862/AI/NIAID NIH HHS/United States ; P30 GM110768/GM/NIGMS NIH HHS/United States ; P30 MH062261/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Immune System ; Mice ; Mice, Inbred NOD ; *Models, Animal ; RNA, Ribosomal, 16S ; }, abstract = {Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut microbiome. NOD.Cg-Prkdc[scid]Il2rg[tm1Wjl]/SzJ (NSG) mice are one of the best animals for humanization due to their high level of immunodeficiency. However, germ-free NSG mice, and various other important germ-free mice models are not currently commercially available. Further, many research settings do not have access to gnotobiotic facilities, and working under gnotobiotic conditions can often be expensive and time consuming. Importantly, germ-free mice have several immune deficiencies that exist even after the engraftment of microbes. Therefore, we developed a protocol that does not require germ-free animals or gnotobiotic facilities. To generate double hu-mice, NSG mice were treated with radiation prior to surgery to create bone-marrow, liver, thymus-humanized (hu-BLT) mice. The mice were then treated with broad spectrum antibiotics to deplete the pre-existing murine gut microbiome. After antibiotic treatment, the mice were given fecal transplants with healthy human donor samples via oral gavage. Double hu-BLT mice had unique 16S rRNA gene profiles based on the individual human donor sample that was transplanted. Importantly, the transplanted human-like microbiome was stable in the double hu-BLT mice for the duration of the study up to 14.5 weeks post-transplant.}, }
@article {pmid31519656, year = {2019}, author = {McCormack, UM and Curião, T and Metzler-Zebeli, BU and Wilkinson, T and Reyer, H and Crispie, F and Cotter, PD and Creevey, CJ and Gardiner, GE and Lawlor, PG}, title = {Improvement of Feed Efficiency in Pigs through Microbial Modulation via Fecal Microbiota Transplantation in Sows and Dietary Supplementation of Inulin in Offspring.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {22}, pages = {}, pmid = {31519656}, issn = {1098-5336}, mesh = {Animal Feed/analysis ; Animals ; Bacteria/classification/isolation &amp; purification ; *Body Weight ; *Dietary Supplements ; Energy Metabolism ; Fecal Microbiota Transplantation/*veterinary ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Inulin/*administration &amp; dosage ; Pregnancy ; Swine/growth &amp; development ; Weaning ; }, abstract = {As previous studies have demonstrated a link between the porcine intestinal microbiome and feed efficiency (FE), microbiota manipulation may offer a means of improving FE in pigs. A fecal microbiota transplantation procedure (FMTp), using fecal extracts from highly feed-efficient pigs, was performed in pregnant sows (n = 11), with a control group (n = 11) receiving no FMTp. At weaning, offspring were allocated, within sow treatment, to (i) control (n = 67; no dietary supplement) or (ii) inulin (n = 65; 6-week dietary inulin supplementation) treatments. The sow FMTp, alone or in combination with inulin supplementation in offspring, reduced offspring body weight by 8.1 to 10.6 kg at ∼140 days of age, but there was no effect on feed intake. It resulted in better FE, greater bacterial diversity, and higher relative abundances of potentially beneficial bacterial taxa (Fibrobacter and Prevotella) in offspring. Due to the FMTp and/or inulin supplementation, relative abundances of potential pathogens (Chlamydia and Treponema) in the ileum and cecal concentrations of butyric acid were significantly lower. The maternal FMTp led to a greater number of jejunal goblet cells in offspring. Inulin supplementation alone did not affect growth or FE but upregulated duodenal genes linked to glucose and volatile fatty acid homeostasis and increased the mean platelet volume but reduced ileal propionic acid concentrations, granulocyte counts, and serum urea concentrations. Overall, the FMTp in pregnant sows, with or without dietary inulin supplementation in offspring, beneficially modulated offspring intestinal microbiota (albeit mostly low-relative-abundance taxa) and associated physiological parameters. Although FE was improved, the detrimental effect on growth limits the application of this FMTp-inulin strategy in commercial pig production.IMPORTANCE As previous research suggests a link between microbiota and FE, modulation of the intestinal microbiome may be effective in improving FE in pigs. The FMTp in gestating sows, alone or in combination with postweaning dietary inulin supplementation in offspring, achieved improvements in FE and resulted in a higher relative abundance of intestinal bacteria associated with fiber degradation and a lower relative abundance of potential pathogens. However, there was a detrimental effect on growth, although this may not be wholly attributable to microbiota transplantation, as antibiotic and other interventions were also part of the FMT regimen. Therefore, further work with additional control groups is needed to disentangle the effects of each component of the FMTp in order to develop a regimen with practical applications in pig production. Additional research based on findings from this study may also identify specific dietary supplements for the promotion/maintenance of the microbiota transferred via the maternal FMTp, thereby optimizing pig growth and FE.}, }
@article {pmid31519210, year = {2019}, author = {Ingham, AC and Kielsen, K and Cilieborg, MS and Lund, O and Holmes, S and Aarestrup, FM and Müller, KG and Pamp, SJ}, title = {Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {131}, pmid = {31519210}, issn = {2049-2618}, mesh = {Adolescent ; Biomarkers/blood ; Child ; Child, Preschool ; Cohort Studies ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; Graft vs Host Disease/*immunology/*microbiology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Infant ; Lactobacillaceae/*immunology/isolation &amp; purification ; Male ; Transplantation, Homologous ; }, abstract = {BACKGROUND: Increasing evidence reveals the importance of the microbiome in health and disease and inseparable host-microbial dependencies. Host-microbe interactions are highly relevant in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), i.e., a replacement of the cellular components of the patients' immune system with that of a foreign donor. HSCT is employed as curative immunotherapy for a number of non-malignant and malignant hematologic conditions, including cancers such as acute lymphoblastic leukemia. The procedure can be accompanied by severe side effects such as infections, acute graft-versus-host disease (aGvHD), and death. Here, we performed a longitudinal analysis of immunological markers, immune reconstitution and gut microbiota composition in relation to clinical outcomes in children undergoing HSCT. Such an analysis could reveal biomarkers, e.g., at the time point prior to HSCT, that in the future could be used to predict which patients are of high risk in relation to side effects and clinical outcomes and guide treatment strategies accordingly.<br><br>RESULTS: In two multivariate analyses (sparse partial least squares regression and canonical correspondence analysis), we identified three consistent clusters: (1) high concentrations of the antimicrobial peptide human beta-defensin 2 (hBD2) prior to the transplantation in patients with high abundances of Lactobacillaceae, who later developed moderate or severe aGvHD and exhibited high mortality. (2) Rapid reconstitution of NK and B cells in patients with high abundances of obligate anaerobes such as Ruminococcaceae, who developed no or mild aGvHD and exhibited low mortality. (3) High inflammation, indicated by high levels of C-reactive protein, in patients with high abundances of facultative anaerobic bacteria such as Enterobacteriaceae. Furthermore, we observed that antibiotic treatment influenced the bacterial community state.<br><br>CONCLUSIONS: We identify multivariate associations between specific microbial taxa, host immune markers, immune cell reconstitution, and clinical outcomes in relation to HSCT. Our findings encourage further investigations into establishing longitudinal surveillance of the intestinal microbiome and relevant immune markers, such as hBD2, in HSCT patients. Profiling of the microbiome may prove useful as a prognostic tool that could help identify patients at risk of poor immune reconstitution and adverse outcomes, such as aGvHD and death, upon HSCT, providing actionable information in guiding precision medicine.}, }
@article {pmid31518024, year = {2020}, author = {Zhao, W and Hu, Y and Li, C and Li, N and Zhu, S and Tan, X and Li, M and Zhang, Y and Xu, Z and Ding, Z and Hu, L and Liu, Z and Sun, J}, title = {Transplantation of fecal microbiota from patients with alcoholism induces anxiety/depression behaviors and decreases brain mGluR1/PKC ε levels in mouse.}, journal = {BioFactors (Oxford, England)}, volume = {46}, number = {1}, pages = {38-54}, doi = {10.1002/biof.1567}, pmid = {31518024}, issn = {1872-8081}, support = {2016GSF201054//Key Research Plan of Shandong Province/ ; 81671320//National Natural Science Foundation of China/ ; 81871044//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Alcoholism/*microbiology/psychology ; Animals ; Anxiety/*microbiology/psychology ; Behavior, Animal ; Brain/*metabolism ; Depression/*microbiology/psychology ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Protein Kinase C-epsilon/*metabolism ; Receptors, Metabotropic Glutamate/*metabolism ; }, abstract = {Recent studies have revealed that the gut microbiota participates in the psychiatric behavior changes in disorders associated with alcohol. But it still remains unknown whether alcoholism is involved in changes in gut microbiota and its underlying mechanism is also not clear. Here, we tested the gut microbiota of patients with alcoholism and conducted fecal microbiota transplantation (FMT) from patients with alcoholism to C57BL/6J mice whose gut microbiota had been sharply suppressed with antibiotics (ABX). Then we evaluated their alcohol preference degree, anxiety, and depression-like behaviors and social interaction behaviors, together with molecular changes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Our data indicated that the gut microbiota of patients with alcoholism was drastically different from those of the healthy adults. The abundance of p_Firmicutes was significantly increased whereas p_Bacteroidetes was decreased. Compared to mice transplanted with fecal microbiota from healthy male adults, the mice accepting fecal microbiota from patients with alcoholism showed (a) anxiety-like and depression-like behaviors, (b) decreased social interaction behaviors, (c) spontaneous alcohol preference, and (d) decreased brain-derived neurotrophic factor (BDNF), alpha 1 subunit of GABA type A receptor (α1GABAA R) in mPFC and decreased metabotropic glutamate receptors 1 (mGluR1), protein kinase C (PKC) ε in NAc. Overall, our results suggest that fecal microbiota from patients with alcoholism did induce a status like alcohol dependence in C57BL/6J mice. The decreased expression of BDNF, α1GABAA R, and mGluR1/ PKC ε may be the underlying mechanism.}, }
@article {pmid31516959, year = {2019}, author = {Posovszky, C and Sirin, M and Jacobsen, E and Lorenz, M and Schwarz, K and Schmidt-Choudhury, A and Schütz, C and Hönig, M and Debatin, KM and Schulz, A and Möller, P and Barth, TF}, title = {Dataset of clinical, immunohistopathological and laboratory features of patients with MHC II deficiency suffering from enteropathy.}, journal = {Data in brief}, volume = {26}, number = {}, pages = {104446}, pmid = {31516959}, issn = {2352-3409}, abstract = {Major histocompatibility complex class II (MHC II) is essential for adaptive immune response. We recently reported on disturbed adaptive mucosal immunity due to MHC II deficiency and prolonged enteropathy. Here, we share medical history, flow cytometric analysis of blood lymphocytes, immunohistopathology, and fecal analysis of seven genetically confirmed patients with MHC II deficiency suffering from enteropathy. Data on flow cytometric analysis of HLA-DR expression on monocytes and B cells before hematopoietic stem cell transplantation (HSCT) and after in-vitro stimulation is shown. The course of immune reconstitution after HSCT of MHC II deficient patients in comparison to severe combined immunodeficiency (SCID) patients is described. In addition, immunohistopathology illustrating CD4 and CD8 T cell infiltration, absence of B lymphocytes and plasma cells, and disturbed immunoglobulin expression in the gut as well as absent HLA-DR expression in the liver is shown. Furthermore, data from fecal analysis such as stool fat, nitrogen, and water fraction as well as faecal markers such as alpha-1-antitrypsin, pancreas specific elastase 1, eosinophilic protein X (EPX), and beta defensin 2 are presented. Altogether this data demonstrates the complex phenotype of MHC II deficiency. The data can be valuable for researchers interested in mucosal immunity. For further interpretation of the data presented in this article, please see the research article "Persisting enteropathy and disturbed adaptive mucosal immunity due to MHC class II deficiency" (Posovszky et al., 2019).}, }
@article {pmid31516555, year = {2019}, author = {Wu, X and Dai, M and Buch, H and Bai, J and Long, W and Long, C and Tang, X and Tu, H and Zhang, R and Zhu, C and Yang, S and Cui, B and Ji, G and Zhang, F}, title = {The recognition and attitudes of postgraduate medical students toward fecal microbiota transplantation: a questionnaire study.}, journal = {Therapeutic advances in gastroenterology}, volume = {12}, number = {}, pages = {1756284819869144}, pmid = {31516555}, issn = {1756-283X}, abstract = {BACKGROUND: Physicians and medical students in the world do not have high awareness of fecal microbiota transplantation (FMT). This study aimed to explore the recognition and attitude of postgraduate medical students towards FMT and to create awareness for it.<br><br>METHODS: A self-administered questionnaire was distributed to first-year Chinese postgraduate medical students across six medical universities. Basic descriptive statistical analyses were performed.<br><br>RESULTS: A total of 1828 eligible questionnaires were included into analysis. 47.76% of students did not know FMT prior to this survey. Respondents with a high-level recognition of FMT were more willing to donate feces or receive FMT therapy than those with a low-level recognition (80.26% vs. 69.62%, p&#x2009;=&#x2009;0.000 and 56.80% vs. 41.45%, p&#x2009;=&#x2009;0.000). The respondents from a leading institution of FMT in China showed better awareness compared with others, and 42.26% of them knew about FMT from medical lectures. The main reasons for respondents not supporting FMT were: limited reported clinical evidence (67.94%), raw technology (42.56%), and lack of analysis of patient willingness or cost-effectiveness (36.71%). However, the life-saving value (84.41%), the automatic purification system (38.68%), low expenses (36.00%), and convenient delivering ways (35.67%) were the major considerations for supporting FMT.<br><br>CONCLUSIONS: This study revealed the low recognition level of postgraduate medical students about FMT. Therefore, medical education should not neglect the knowledge of FMT. Studies of FMT and standardized FMT should be carried out to promote its development.}, }
@article {pmid31512505, year = {2019}, author = {Schepici, G and Silvestro, S and Bramanti, P and Mazzon, E}, title = {The Gut Microbiota in Multiple Sclerosis: An Overview of Clinical Trials.}, journal = {Cell transplantation}, volume = {28}, number = {12}, pages = {1507-1527}, pmid = {31512505}, issn = {1555-3892}, mesh = {*Bacteria/classification/growth &amp; development ; Clinical Trials as Topic ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Multiple Sclerosis/*microbiology/*therapy ; }, abstract = {Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and degenerative disease that affects the central nervous system. A recent study showed that interaction between the immune system and the gut microbiota plays a crucial role in the development of MS. This review reports the clinical studies carried out in recent years that aimed to evaluate the composition of the microbiota in patients with relapsing-remitting MS (RR-MS). We also report what is available in the literature regarding the effectiveness of fecal microbiota transplantation and the role of the diet in restoring the intestinal bacterial population. Studies report that patients with RR-MS have a microbiota that, compared with healthy controls, has higher amounts of Pedobacteria, Flavobacterium, Pseudomonas, Mycoplana, Acinetobacter, Eggerthella, Dorea, Blautia, Streptococcus and Akkermansia. In contrast, MS patients have a microbiota with impoverished microbial populations of Prevotella, Bacteroides, Parabacteroides, Haemophilus, Sutterella, Adlercreutzia, Coprobacillus, Lactobacillus, Clostridium, Anaerostipes and Faecalibacterium. In conclusion, the restoration of the microbial population in patients with RR-MS appears to reduce inflammatory events and the reactivation of the immune system.}, }
@article {pmid31510101, year = {2019}, author = {Prochazkova, P and Roubalova, R and Dvorak, J and Tlaskalova-Hogenova, H and Cermakova, M and Tomasova, P and Sediva, B and Kuzma, M and Bulant, J and Bilej, M and Hrabak, P and Meisnerova, E and Lambertova, A and Papezova, H}, title = {Microbiota, Microbial Metabolites, and Barrier Function in A Patient with Anorexia Nervosa after Fecal Microbiota Transplantation.}, journal = {Microorganisms}, volume = {7}, number = {9}, pages = {}, pmid = {31510101}, issn = {2076-2607}, support = {17-28905A//MINISTRY OF HEALTH OF THE CZECH REPUBLIC/ ; }, abstract = {The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.}, }
@article {pmid31509535, year = {2019}, author = {King, CH and Desai, H and Sylvetsky, AC and LoTempio, J and Ayanyan, S and Carrie, J and Crandall, KA and Fochtman, BC and Gasparyan, L and Gulzar, N and Howell, P and Issa, N and Krampis, K and Mishra, L and Morizono, H and Pisegna, JR and Rao, S and Ren, Y and Simonyan, V and Smith, K and VedBrat, S and Yao, MD and Mazumder, R}, title = {Baseline human gut microbiota profile in healthy people and standard reporting template.}, journal = {PloS one}, volume = {14}, number = {9}, pages = {e0206484}, pmid = {31509535}, issn = {1932-6203}, support = {U01 CA230690/CA/NCI NIH HHS/United States ; R01 CA236591/CA/NCI NIH HHS/United States ; I01 BX003732/BX/BLRD VA/United States ; R01 AA023146/AA/NIAAA NIH HHS/United States ; UL1 TR000075/TR/NCATS NIH HHS/United States ; }, mesh = {Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Metagenome ; *Metagenomics/methods ; }, abstract = {A comprehensive knowledge of the types and ratios of microbes that inhabit the healthy human gut is necessary before any kind of pre-clinical or clinical study can be performed that attempts to alter the microbiome to treat a condition or improve therapy outcome. To address this need we present an innovative scalable comprehensive analysis workflow, a healthy human reference microbiome list and abundance profile (GutFeelingKB), and a novel Fecal Biome Population Report (FecalBiome) with clinical applicability. GutFeelingKB provides a list of 157 organisms (8 phyla, 18 classes, 23 orders, 38 families, 59 genera and 109 species) that forms the baseline biome and therefore can be used as healthy controls for studies related to dysbiosis. This list can be expanded to 863 organisms if closely related proteomes are considered. The incorporation of microbiome science into routine clinical practice necessitates a standard report for comparison of an individual's microbiome to the growing knowledgebase of "normal" microbiome data. The FecalBiome and the underlying technology of GutFeelingKB address this need. The knowledgebase can be useful to regulatory agencies for the assessment of fecal transplant and other microbiome products, as it contains a list of organisms from healthy individuals. In addition to the list of organisms and their abundances, this study also generated a collection of assembled contiguous sequences (contigs) of metagenomics dark matter. In this study, metagenomic dark matter represents sequences that cannot be mapped to any known sequence but can be assembled into contigs of 10,000 nucleotides or higher. These sequences can be used to create primers to study potential novel organisms. All data is freely available from https://hive.biochemistry.gwu.edu/gfkb and NCBI's Short Read Archive.}, }
@article {pmid31504398, year = {2019}, author = {Hata, T and Miyata, N and Takakura, S and Yoshihara, K and Asano, Y and Kimura-Todani, T and Yamashita, M and Zhang, XT and Watanabe, N and Mikami, K and Koga, Y and Sudo, N}, title = {The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice.}, journal = {Endocrinology}, volume = {160}, number = {10}, pages = {2441-2452}, doi = {10.1210/en.2019-00408}, pmid = {31504398}, issn = {1945-7170}, mesh = {Adult ; Animals ; Anorexia Nervosa/*microbiology ; *Behavior, Animal ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Mice ; Mice, Inbred BALB C ; *Weight Gain ; Young Adult ; }, abstract = {Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.}, }
@article {pmid31502737, year = {2019}, author = {Westblade, LF and Satlin, MJ and Albakry, S and Botticelli, B and Robertson, A and Alston, T and Magruder, M and Zhang, LT and Edusei, E and Chan, K and Lubetzky, M and Dadhania, DM and Pamer, EG and Suthanthiran, M and Lee, JR}, title = {Gastrointestinal pathogen colonization and the microbiome in asymptomatic kidney transplant recipients.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {21}, number = {6}, pages = {e13167}, pmid = {31502737}, issn = {1399-3062}, support = {//BioFire Diagnostics, LLC/ ; P30 CA008748/CA/NCI NIH HHS/United States ; R37 AI 051652//National Institute of Allergy and Infectious Diseases/ ; K23 AI124464/AI/NIAID NIH HHS/United States ; K23 AI 124464//National Institute of Allergy and Infectious Diseases/ ; R37 AI051652/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asymptomatic Infections/*epidemiology ; Clostridioides difficile/genetics/isolation &amp; purification ; DNA, Bacterial/isolation &amp; purification ; Dysbiosis/diagnosis/*epidemiology/microbiology ; Enteropathogenic Escherichia coli/genetics/isolation &amp; purification ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Intestinal Mucosa/immunology/microbiology ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Norovirus/genetics/isolation &amp; purification ; RNA, Ribosomal, 16S/genetics ; RNA, Viral/isolation &amp; purification ; Retrospective Studies ; }, abstract = {BACKGROUND: In kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of GI pathogens in asymptomatic individuals in this population.<br><br>METHODS: We recruited 142 kidney transplant recipients who provided a non-diarrheal fecal sample within the first 10&#xa0;days after transplantation. The specimens were evaluated for GI pathogens using the BioFire[&#xae;] FilmArray[&#xae;] GI Panel (BioFire Diagnostics, LLC), which tests for 22 pathogens. The fecal microbiome was also characterized using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We evaluated whether detection of Clostridioides difficile and other GI pathogens was associated with post-transplant diarrhea within the first 3&#xa0;months after transplantation.<br><br>RESULTS: Among the 142 subjects, a potential pathogen was detected in 43 (30%) using the GI Panel. The most common organisms detected were C&#xa0;difficile (n&#xa0;=&#xa0;24, 17%), enteropathogenic Escherichia coli (n&#xa0;=&#xa0;8, 6%), and norovirus (n&#xa0;=&#xa0;5, 4%). Detection of a pathogen on the GI panel or detection of C&#xa0;difficile alone was not associated with future post-transplant diarrhea (P&#xa0;>&#xa0;.05). The estimated number of gut bacterial species was significantly lower in subjects colonized with C&#xa0;difficile than those not colonized with&#xa0;a GI pathogen (P&#xa0;=&#xa0;.01).<br><br>CONCLUSION: Colonization with GI pathogens, particularly C&#xa0;difficile, is common at the time of kidney transplantation but does not predict subsequent diarrhea. Detection of C&#xa0;difficile carriage was associated with decreased microbial diversity and may be a biomarker of gut dysbiosis.}, }
@article {pmid31501716, year = {2019}, author = {Lee, H and Kim, J and An, J and Lee, S and Choi, D and Kong, H and Song, Y and Park, IH and Lee, CK and Kim, K}, title = {Downregulation of IL-18 Expression in the Gut by Metformin-induced Gut Microbiota Modulation.}, journal = {Immune network}, volume = {19}, number = {4}, pages = {e28}, pmid = {31501716}, issn = {1598-2629}, abstract = {IL-18 is a crucial pro-inflammatory cytokine that mediates chronic intestinal inflammation. Metformin, an anti-diabetic drug, was reported to have ameliorative effects on inflammatory bowel disease. Recently, the mechanism of action of metformin was explained as a modulation of gut microbiota. In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet. Further, FMT downregulated the expression of the inflammatory cytokine IL-18. Within the genera Akkermansia, Bacteroides, and Butyricimonas, which were promoted by metformin therapy, Butyricimonas was found to be consistently abundant following FMT. Our findings suggest that modulation of gut microbiota is a key factor for the anti-inflammatory effects of metformin which is used for the treatment of hyperglycemia.}, }
@article {pmid31501515, year = {2019}, author = {Spalinger, MR and Schwarzfischer, M and Hering, L and Shawki, A and Sayoc, A and Santos, A and Gottier, C and Lang, S and Bäbler, K and Geirnaert, A and Lacroix, C and Leventhal, GE and Dai, X and Rawlings, D and Chan, AA and Rogler, G and McCole, DF and Scharl, M}, title = {Loss of PTPN22 abrogates the beneficial effect of cohousing-mediated fecal microbiota transfer in murine colitis.}, journal = {Mucosal immunology}, volume = {12}, number = {6}, pages = {1336-1347}, pmid = {31501515}, issn = {1935-3456}, mesh = {Animals ; Bacteria/*growth &amp; development/immunology ; Cells, Cultured ; Colitis/enzymology/genetics/microbiology/*therapy ; Colon/*enzymology/immunology/microbiology ; Dextran Sulfate ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Genotype ; *Housing, Animal ; Intestinal Mucosa/*enzymology/immunology/microbiology ; Mice, Inbred C57BL ; Mice, Knockout ; Protein Tyrosine Phosphatase, Non-Receptor Type 22/*deficiency/genetics ; Th1 Cells/immunology/metabolism/microbiology ; }, abstract = {Fecal microbiota transfer (FMT) is a very efficient approach for the treatment of severe and recurring C. difficile infections. However, the beneficial effect of FMT in other disorders such as ulcerative colitis (UC) or Crohn's disease remains unclear. Furthermore, it is currently unknown how disease-associated genetic variants in donors or recipients influence the effect of FMT. We found that bacteria-transfer from wild-type (WT) donors via cohousing was efficient in inducing recovery from colitis in WT mice, but not in mice deficient in protein-tyrosine phosphatase non-receptor type 22 (PTPN22), a known risk gene for several chronic inflammatory diseases. Also cohousing of PTPN22-deficient mice with diseased WT mice failed to induce faster recovery. Our data indicate that the genetic background of the donor and the recipient influences the outcome of microbiota transfer, and offers a potential explanation why transfer of fecal microbes from some, but not all donors is efficient in UC patients.}, }
@article {pmid31496843, year = {2019}, author = {Philips, CA and Augustine, P and Yerol, PK and Rajesh, S and Mahadevan, P}, title = {Severe alcoholic hepatitis: current perspectives.}, journal = {Hepatic medicine : evidence and research}, volume = {11}, number = {}, pages = {97-108}, pmid = {31496843}, issn = {1179-1535}, abstract = {Severe acute alcoholic hepatitis (AH) is a catastrophic disease in the natural history of alcoholic liver disease with a very high 180-day mortality. It can present as acute on chronic liver failure with worse prognosis in the presence of infections and higher grades of liver disease severity. The clinical scenario involves a patient with a recent history of heavy alcohol consumption within three months of presentation with jaundice and characteristic liver enzyme elevation pattern with coagulopathy, hepatic encephalopathy, variceal bleeding and sepsis that results in extrahepatic organ failures. Several liver disease severities and therapy response indicators are in clinical use. Even though not approved, the only recommended treatment option for patients with severe AH is corticosteroids, which is without long term survival benefit. Novel efficacious treatment options awaiting high-quality multi-center studies include liver transplantation (involves strict selection criteria), growth factor therapy and fecal microbiota transplantation. In this exhaustive review, we discuss the definitions, disease severity, histopathology, and treatment options - past, present, and future, in patients with severe alcoholic hepatitis.}, }
@article {pmid31496168, year = {2019}, author = {Hu, Y and Lyu, B}, title = {[Development and prospects of fecal microbiota transplantation].}, journal = {Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences}, volume = {48}, number = {3}, pages = {342-346}, pmid = {31496168}, issn = {1008-9292}, mesh = {*Fecal Microbiota Transplantation/standards/trends ; Humans ; Treatment Outcome ; }, }
@article {pmid31494778, year = {2019}, author = {Yinda, CK and Esefeld, J and Peter, HU and Matthijnssens, J and Zell, R}, title = {Penguin megrivirus, a novel picornavirus from an Adélie penguin (Pygoscelis adeliae).}, journal = {Archives of virology}, volume = {164}, number = {11}, pages = {2887-2890}, doi = {10.1007/s00705-019-04404-9}, pmid = {31494778}, issn = {1432-8798}, support = {Peter_94003-3_338//Bundesministerium f&#xfc;r Umwelt, Naturschutz und Reaktorsicherheit/ ; }, mesh = {3' Untranslated Regions/genetics ; Animals ; Antarctic Regions ; Genome, Viral/*genetics ; Phylogeny ; Picornaviridae/classification/*genetics/isolation &amp; purification ; Spheniscidae/*virology ; }, abstract = {The complete genome sequence of a novel megrivirus of the family Picornaviridae was determined from nucleic acid extracted from a pool of six faecal specimens of Adélie penguins. The samples were collected near Bellingshausen Station, King George Island of the South Shetland Islands, Antarctica. Penguin megrivirus is the first megrivirus with a predicted L protein. It has an L-3-5-4 genome layout, a type IV IRES, and a long 3' untranslated region of 668 nt.}, }
@article {pmid31493521, year = {2019}, author = {Fielding, RA and Reeves, AR and Jasuja, R and Liu, C and Barrett, BB and Lustgarten, MS}, title = {Muscle strength is increased in mice that are colonized with microbiota from high-functioning older adults.}, journal = {Experimental gerontology}, volume = {127}, number = {}, pages = {110722}, pmid = {31493521}, issn = {1873-6815}, support = {K01 AG050700/AG/NIA NIH HHS/United States ; K23 AG057813/AG/NIA NIH HHS/United States ; P30 AG031679/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Animals ; Bacteroidetes/isolation &amp; purification/physiology ; Body Composition/physiology ; Exercise/*physiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Muscle Strength/*physiology ; Muscle, Skeletal/physiology ; Prevotella/isolation &amp; purification/physiology ; Sarcopenia/physiopathology ; }, abstract = {Evidence in support of a gut-muscle axis has been reported in rodents, but studies in older adult humans are limited. Accordingly, the primary goals of the present study were to compare gut microbiome composition in older adults that differed in terms of the percentage of whole body lean mass and physical functioning (high-functioning, HF, n = 18; low-functioning, LF, n = 11), and to evaluate the causative role of the gut microbiome on these variables by transferring fecal samples from older adults into germ-free mice. Family-level Prevotellaceae, genus-level Prevotella and Barnesiella, and the bacterial species Barnesiella intestinihominis were higher in HF older adults at the initial study visit, at a 1-month follow-up visit, in HF human fecal donors, and in HF-colonized mice, when compared with their LF counterparts. Grip strength was significantly increased by 6.4% in HF-, when compared with LF-colonized mice. In contrast, despite significant differences for the percentage of whole body lean mass and physical functioning when comparing the human fecal donors, the percentage of whole body lean mass and treadmill endurance capacity were not different when comparing human microbiome-containing mice. In sum, these data suggest a role for gut bacteria on the maintenance of muscle strength, but argue against a role for gut bacteria on the maintenance of the percentage of whole body lean mass or endurance capacity, findings that collectively add to elucidation of the gut-muscle axis in older adults.}, }
@article {pmid31493500, year = {2020}, author = {Madoff, SE and Urquiaga, M and Alonso, CD and Kelly, CP}, title = {Prevention of recurrent Clostridioides difficile infection: A systematic review of randomized controlled trials.}, journal = {Anaerobe}, volume = {61}, number = {}, pages = {102098}, doi = {10.1016/j.anaerobe.2019.102098}, pmid = {31493500}, issn = {1095-8274}, mesh = {Anti-Bacterial Agents/administration &amp; dosage/adverse effects/therapeutic use ; *Clostridioides difficile ; Clostridium Infections/drug therapy/*microbiology/*prevention &amp; control ; Combined Modality Therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome ; }, abstract = {Recurrent Clostridioides (formerly Clostridium) difficile infection (rCDI) is common, and patients who have had one recurrence are more likely to have multiple recurrences. Frequent recurrences have been associated with increased morbidity and mortality, high healthcare costs, and lower quality of life. In this review, we compare the efficacy of interventions designed to prevent rCDI. We performed a systematic review of the English literature, including randomized controlled trials (RCTs) that evaluated rCDI as an outcome. Studies were included irrespective of patient demographics, disease severity, type of intervention, comparator used, or time-point of outcome evaluation. We performed a comprehensive literature search with the assistance of a research librarian. Two reviewers independently extracted data and assessed risk of bias. Our search yielded 38 RCTs (8,102 participants). Nineteen RCTs (3,743 subjects) evaluated antibiotics, eight fecal microbiota transplantation (FMT) (582 subjects), three monoclonal antibodies (MAbs) (2,805 subjects), and eight probiotics, prebiotics, or non-antibiotic polymers (972 subjects). The antibiotic and FMT therapies that demonstrated efficacy in rCDI prevention included: fidaxomicin (when compared to a ten-day vancomycin course) and FMT administered by nasogastric tube (when compared to a fourteen-day vancomycin course and a fourteen-day vancomycin course plus bowel lavage). Actoxumab (MAb against C. difficile toxin A; CDA1) plus bezlotoxumab (MAb against C. difficile toxin B; CDB1) in combination or bezlotoxumab alone appeared to be more effective in preventing rCDI compared to actoxumab alone. Of the prebiotics, probiotics, and nonantibiotic polymers, oligofructose, Saccharomyces boulardii, and the nontoxigenic C. difficile strain M3 were the most efficacious for rCDI prevention. Thirty-eight RCTs (>8,000 participants) evaluating treatment modalities for CDI were examined for efficacy in prevention of rCDI. Several CDI-specific antibiotics, FMT modalities, monoclonal antibodies, and various prebiotics and probiotics demonstrated a reduction in risk of rCDI with the greatest risk reduction observed with FMT and monoclonal antibody therapy. It is notable that the comparators in these studies were very different from one another and the relative risk reduction of rCDI may not be directly comparable from one study to the next.}, }
@article {pmid31493042, year = {2020}, author = {Luo, Y and Lucas, AL and Grinspan, AM}, title = {Fecal Transplants by Colonoscopy and Capsules Are Cost-Effective Strategies for Treating Recurrent Clostridioides difficile Infection.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {4}, pages = {1125-1133}, pmid = {31493042}, issn = {1573-2568}, mesh = {Administration, Oral ; Aged ; Capsules ; *Clostridioides difficile ; Clostridium Infections/*economics/*therapy ; Colonoscopy/*economics/methods ; *Cost-Benefit Analysis ; Fecal Microbiota Transplantation/*economics/methods ; Humans ; Models, Economic ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Recurrent Clostridioides difficile infections (CDIs) occur frequently and pose a substantial economic burden on the US healthcare system. The landscape for the treatment of CDI is evolving.<br><br>AIM: To elucidate the most cost-effective strategy for managing recurrent CDI.<br><br>METHODS: A decision tree analysis was created from a modified third-party payer's perspective to compare the cost-effectiveness of five strategies for patients experiencing their first CDI recurrence: oral vancomycin, fidaxomicin, fecal microbiota transplant (FMT) via colonoscopy, FMT via oral capsules, and a one-time infusion of bezlotoxumab with vancomycin. Effectiveness measures were quality-adjusted life years (QALY). A willingness-to-pay (WTP) threshold of $100,000 per QALY was set. One-way and probabilistic sensitivity analyses were performed.<br><br>RESULTS: Base-case analysis showed that FMT via colonoscopy was associated with the lowest cost at $5250 and that FMT via capsules was also a cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of $31205/QALY. Sensitivity analyses demonstrated that FMT delivered by oral capsules and colonoscopy was comparable cost-effective modalities. At its current cost and effectiveness, bezlotoxumab was not a cost-effective strategy.<br><br>CONCLUSIONS: FMT via oral capsules and colonoscopy is both cost-effective strategies to treat the first recurrence of CDI. Further real-world economic studies are needed to understand the cost-effectiveness of all available strategies.}, }
@article {pmid31492846, year = {2019}, author = {Guo, H and Li, Y and Liu, G and Jiang, Y and Shen, S and Bi, R and Huang, H and Cheng, T and Wang, C and Wei, W}, title = {A second open reading frame in human enterovirus determines viral replication in intestinal epithelial cells.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {4066}, pmid = {31492846}, issn = {2041-1723}, mesh = {Amino Acid Sequence ; Base Sequence ; Enterovirus/*genetics/physiology ; Enterovirus Infections/transmission/virology ; Epithelial Cells/virology ; Feces/virology ; HT29 Cells ; Host-Pathogen Interactions/genetics ; Humans ; Intestines/cytology/virology ; Open Reading Frames/*genetics ; RNA Viruses/*genetics/physiology ; Viral Proteins/genetics/metabolism ; Virus Replication/*genetics ; }, abstract = {Human enteroviruses (HEVs) of the family Picornaviridae, which comprises non-enveloped RNA viruses, are ubiquitous worldwide. The majority of EV proteins are derived from viral polyproteins encoded by a single open reading frame (ORF). Here, we characterize a second ORF in HEVs that is crucial for viral intestinal infection. Disruption of ORF2p expression decreases the replication capacity of EV-A71 in human intestinal epithelial cells (IECs). Ectopic expression of ORF2p proteins derived from diverse enteric enteroviruses sensitizes intestinal cells to the replication of ORF2p-defective EV-A71 and respiratory enterovirus EV-D68. We show that the highly conserved WIGHPV domain of ORF2p is important for ORF2p-dependent viral intestinal infection. ORF2p expression is required for EV-A71 particle release from IECs and can support productive EV-D68 infection in IECs by facilitating virus release. Our results indicate that ORF2p is a determining factor for enteric enterovirus replication in IECs.}, }
@article {pmid31492463, year = {2020}, author = {Chong, PP and Koh, AY}, title = {The gut microbiota in transplant patients.}, journal = {Blood reviews}, volume = {39}, number = {}, pages = {100614}, pmid = {31492463}, issn = {1532-1681}, support = {R01 AI123163/AI/NIAID NIH HHS/United States ; }, mesh = {Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Hematopoietic Stem Cell Transplantation/*methods ; Humans ; Organ Transplantation/*methods ; Transplantation Conditioning/*methods ; }, abstract = {Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients are at increased risk for developing infections due to underlying immunosuppression. Antibiotic use, and in HSCT recipients, the use of preparative regimens prior to transplantation can deplete gut commensal bacteria, resulting in intestinal dysbiosis. Emerging evidence in transplant patients, particularly HSCT, suggest that disturbances in gut microbiota populations are associated with a number of adverse outcomes. Here, we review the outcomes of HSCT and SOT recipients with gut microbiota imbalance or dysbiosis, explore the nascent field of gut microbiome therapeutic approaches including fecal microbiota transplantation and the use of precision probiotics in HSCT and SOT recipients.}, }
@article {pmid31487251, year = {2019}, author = {Martínez, JV and Raush, A and Efrón, ED and Zubiaurre, I and Pinoni, MV and Giorgio, PL and Eusebio, MJ and Verbanaz, SC and Jordan, R}, title = {[Refractory colitis by Clostridium difficile treated with fecal microbiota transplant].}, journal = {Medicina}, volume = {79}, number = {4}, pages = {291-294}, pmid = {31487251}, issn = {1669-9106}, mesh = {Aged, 80 and over ; *Clostridioides difficile ; Clostridium Infections/complications/*therapy ; Diarrhea/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Treatment Outcome ; }, abstract = {Clostridium difficile infection is an increasingly recognized cause of diarrhea in inpatients, frequently associated to high mortality. Vancomycin is the treatment of choice for all Clostridium difficile- associated diarrheas, with different degrees of severity. However, some patients develop refractory forms to that treatment and there are no alternative antibiotic schemes recommended for these cases. Fecal microbiota transplantation has been shown to be successful in a series of cases of severe diarrhea associated with this organism. We present a case of refractory C. difficile infection successfully treated with fecal microbiota transplantation.}, }
@article {pmid31482438, year = {2020}, author = {Mishima, Y and Sartor, RB}, title = {Manipulating resident microbiota to enhance regulatory immune function to treat inflammatory bowel diseases.}, journal = {Journal of gastroenterology}, volume = {55}, number = {1}, pages = {4-14}, pmid = {31482438}, issn = {1435-5922}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Dysbiosis/complications/diagnosis/immunology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Homeostasis ; Humans ; *Immunity, Mucosal ; Inflammatory Bowel Diseases/immunology/*microbiology/*therapy ; Prebiotics ; Probiotics/therapeutic use ; Treatment Outcome ; }, abstract = {Altered intestinal microbial composition (dysbiosis) and metabolic products activate aggressive mucosal immune responses that mediate inflammatory bowel diseases (IBD). This dysbiosis impairs the function of regulatory immune cells, which normally promote mucosal homeostasis. Normalizing and maintaining regulatory immune cell function by correcting dysbiosis provides a promising approach to treat IBD patients. However, existing microbe-targeted therapies, including antibiotics, prebiotics, probiotics, and fecal microbial transplantation, provide variable outcomes that are not optimal for current clinical application. This review discusses recent progress in understanding the dysbiosis of IBD and the basis for therapeutic restoration of homeostatic immune function by manipulating an individual patient's microbiota composition and function. We believe that identifying more precise therapeutic targets and developing appropriate rapid diagnostic tools will guide more effective and safer microbe-based induction and maintenance treatments for IBD patients that can be applied in a personalized manner.}, }
@article {pmid31476300, year = {2019}, author = {Monaghan, TM and Pučić-Baković, M and Vučković, F and Lee, C and Kao, D and , }, title = {Decreased Complexity of Serum N-glycan Structures Associates with Successful Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Gastroenterology}, volume = {157}, number = {6}, pages = {1676-1678.e3}, doi = {10.1053/j.gastro.2019.08.034}, pmid = {31476300}, issn = {1528-0012}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Aged ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/blood/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Glycosylation ; Humans ; Male ; Middle Aged ; Polysaccharides/*blood/metabolism ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Treatment Outcome ; }, }
@article {pmid31475811, year = {2019}, author = {Castro, I and Tasias, M and Calabuig, E and Salavert, M}, title = {Doctor, my patient has CDI and should continue to receive antibiotics. The (unresolved) risk of recurrent CDI.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {32 Suppl 2}, number = {Suppl 2}, pages = {47-54}, pmid = {31475811}, issn = {1988-9518}, mesh = {Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile ; Clostridium Infections/*drug therapy ; Enterocolitis, Pseudomembranous/drug therapy ; Humans ; Recurrence ; }, abstract = {Recurrence rate ranges from 12% to 40% of all cases of Clostridium difficile infection (CDI) and proposes an exceptional clinical challenge. Conventionally, treatment options of CDI have been limited to regimes of established antibiotics (eg, pulsed/tapered vancomycin) or "improvised" alternative antibiotics (eg. teicoplanin, tigecycline, nitazoxanide or rifaximin) occasionally even in combination, but faecal microbiota transplantation is emerging as a useful and quite safe alternative. In recent years, promising new strategies have emerged for effective prevention of recurrent CDI (rCDI) including new an-timicrobials (eg, fidaxomicin) and monoclonal antibodies (eg, bezlotoxumab). Despite promising progress in this area, difficulties remain for making the best use of these resources due to uncertainty over patient selection. This positioning review describes the current epidemiology of rCDI, its clinical impact and risk factors, some of the measures used for treating and preventing rCDI, and some of the emerging treatment options. It then describes some of the barriers that need to be overcome.}, }
@article {pmid31472233, year = {2019}, author = {Tan, X and Johnson, S}, title = {Fecal microbiota transplantation (FMT) for C. difficile infection, just say 'No'.}, journal = {Anaerobe}, volume = {60}, number = {}, pages = {102092}, doi = {10.1016/j.anaerobe.2019.102092}, pmid = {31472233}, issn = {1095-8274}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*physiology ; Clostridium Infections/*microbiology/*therapy ; Disease Management ; *Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {Despite lack of regulatory approval, fecal microbiota transplantation (FMT) is widely performed to manage C. difficile infection (CDI), particularly recurrent CDI. Herein, we critically review the available randomized controlled trials of FMT and address the following questions: Is FMT better than drug management of recurrent CDI?; Is FMT treatment per se or adjunctive treatment to antibiotics for CDI?; and, Is FMT safe? Finally, we elaborate non-FMT options for the management of recurrent CDI. Although promising, FMT should be reserved for patients who have failed appropriate antibiotic management of recurrent CDI.}, }
@article {pmid31471351, year = {2020}, author = {Kim, MS and Kim, Y and Choi, H and Kim, W and Park, S and Lee, D and Kim, DK and Kim, HJ and Choi, H and Hyun, DW and Lee, JY and Choi, EY and Lee, DS and Bae, JW and Mook-Jung, I}, title = {Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer's disease animal model.}, journal = {Gut}, volume = {69}, number = {2}, pages = {283-294}, doi = {10.1136/gutjnl-2018-317431}, pmid = {31471351}, issn = {1468-3288}, mesh = {Alzheimer Disease/metabolism/*microbiology/*therapy ; Animals ; Behavior, Animal ; Chronic Disease ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/microbiology ; Intestines/microbiology ; Memory, Short-Term ; Mice, Transgenic ; Permeability ; Plaque, Amyloid/microbiology/pathology ; Spatial Learning ; tau Proteins/analysis ; }, abstract = {OBJECTIVE: Cerebral amyloidosis and severe tauopathy in the brain are key pathological features of Alzheimer's disease (AD). Despite a strong influence of the intestinal microbiota on AD, the causal relationship between the gut microbiota and AD pathophysiology is still elusive.<br><br>DESIGN: Using a recently developed AD-like pathology with amyloid and neurofibrillary tangles (ADLP[APT]) transgenic mouse model of AD, which shows amyloid plaques, neurofibrillary tangles and reactive gliosis in their brains along with memory deficits, we examined the impact of the gut microbiota on AD pathogenesis.<br><br>RESULTS: Composition of the gut microbiota in ADLP[APT] mice differed from that of healthy wild-type (WT) mice. Besides, ADLP[APT] mice showed a loss of epithelial barrier integrity and chronic intestinal and systemic inflammation. Both frequent transfer and transplantation of the faecal microbiota from WT mice into ADLP[APT] mice ameliorated the formation of amyloid &#x3b2; plaques and neurofibrillary tangles, glial reactivity and cognitive impairment. Additionally, the faecal microbiota transfer reversed abnormalities in the colonic expression of genes related to intestinal macrophage activity and the circulating blood inflammatory monocytes in the ADLP[APT] recipient mice.<br><br>CONCLUSION: These results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD in ADLP[APT] mice, providing new insights into the relationship between the gut (colonic gene expression, gut permeability), blood (blood immune cell population) and brain (pathology) axis and AD (memory deficits). Thus, restoring gut microbial homeostasis may have beneficial effects on AD treatment.}, }
@article {pmid31469291, year = {2019}, author = {Ahmad, AF and Dwivedi, G and O'Gara, F and Caparros-Martin, J and Ward, NC}, title = {The gut microbiome and cardiovascular disease: current knowledge and clinical potential.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {317}, number = {5}, pages = {H923-H938}, doi = {10.1152/ajpheart.00376.2019}, pmid = {31469291}, issn = {1522-1539}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Arteries/metabolism/*microbiology/pathology ; Atherosclerosis/metabolism/*microbiology/pathology/therapy ; Bacteria/*metabolism ; Diet, Healthy ; Dietary Supplements ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology ; Plaque, Atherosclerotic ; Signal Transduction ; }, abstract = {Cardiovascular disease (CVD) is the leading cause of death worldwide. The human body is populated by a diverse community of microbes, dominated by bacteria, but also including viruses and fungi. The largest and most complex of these communities is located in the gastrointestinal system and, with its associated genome, is known as the gut microbiome. Gut microbiome perturbations and related dysbiosis have been implicated in the progression and pathogenesis of CVD, including atherosclerosis, hypertension, and heart failure. Although there have been advances in the characterization and analysis of the gut microbiota and associated bacterial metabolites, the exact mechanisms through which they exert their action are not well understood. This review will focus on the role of the gut microbiome and associated functional components in the development and progression of atherosclerosis. Potential treatments to alter the gut microbiome to prevent or treat atherosclerosis and CVD are also discussed.}, }
@article {pmid31468999, year = {2019}, author = {Yoon, YK and Suh, JW and Kang, EJ and Kim, JY}, title = {Efficacy and safety of fecal microbiota transplantation for decolonization of intestinal multidrug-resistant microorganism carriage: beyond Clostridioides difficile infection.}, journal = {Annals of medicine}, volume = {51}, number = {7-8}, pages = {379-389}, pmid = {31468999}, issn = {1365-2060}, mesh = {*Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Persistent reservoirs of multidrug-resistant microorganisms (MDRO) that are prevalent in hospital settings and communities can lead to the spread of MDRO. Currently, there are no effective decolonization strategies, especially non-pharmacological strategies without antibiotic regimens. Our aim was to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the eradication of MDRO. A systematic literature search was performed to identify studies on the use of FMT for the decolonization of MDRO. PubMed, EMBASE, Web of Science, and Cochrane Library were searched from inception through January 2019. Of the 1395 articles identified, 20 studies met the inclusion and exclusion criteria. Overall, the efficacy of FMT for the eradication of each MDRO was 70.3% (102/146) in 121 patients from the 20 articles. The efficacy rates were 68.2% (30/44) for gram-positive bacteria and 70.6% (72/102) for gram-negative bacteria. Minor adverse events, including vomiting, diarrhea, abdominal pain, and ileus, were reported in patients who received FMT. FMT could be a promising strategy to eradicate MDRO in patients. Further studies are needed to confirm these findings and establish a comprehensive FMT protocol for standardized treatment.Key messagesThe development of new antibiotics lags behind the emergence of multidrug-resistant microorganisms (MDRO). New strategies are needed.Theoretically, fecal microbiota transplantation (FMT) might recover the diversity and function of commensal microbiota from dysbiosis in MDRO carriers and help restore colonization resistance to pathogens.A literature review indicated that FMT could be a promising strategy to eradicate MDRO in patients.}, }
@article {pmid31467881, year = {2019}, author = {Zhou, Y and Xu, H and Huang, H and Li, Y and Chen, H and He, J and Du, Y and Chen, Y and Zhou, Y and Nie, Y}, title = {Are There Potential Applications of Fecal Microbiota Transplantation beyond Intestinal Disorders?.}, journal = {BioMed research international}, volume = {2019}, number = {}, pages = {3469754}, pmid = {31467881}, issn = {2314-6141}, mesh = {Clostridioides difficile/pathogenicity ; Clostridium Infections/microbiology/pathology/therapy ; Fecal Microbiota Transplantation/*trends ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Intestinal Diseases/microbiology/pathology/*therapy ; Intestines/microbiology ; Irritable Bowel Syndrome/microbiology/*therapy ; }, abstract = {Intestinal microbial dysbiosis is associated with various intestinal and extraintestinal disorders. Fecal microbiota transplantation (FMT), a type of fecal bacteriotherapy, is considered an effective therapeutic option for recurrent Clostridium difficile infection (rCDI) and also has important value in other intestinal diseases including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). The purpose of this review is to discuss promising therapeutic value in extraintestinal diseases associated with gut microbial dysbiosis, including liver, metabolic, chronic kidney, neuropsychiatric, allergic, autoimmune, and hematological diseases as well as tumors.}, }
@article {pmid31467135, year = {2019}, author = {Wang, S and Lv, D and Jiang, S and Jiang, J and Liang, M and Hou, F and Chen, Y}, title = {Quantitative reduction in short-chain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease.}, journal = {Clinical science (London, England : 1979)}, volume = {133}, number = {17}, pages = {1857-1870}, doi = {10.1042/CS20190171}, pmid = {31467135}, issn = {1470-8736}, mesh = {Animals ; Butyrates/blood/*metabolism ; Case-Control Studies ; Disease Models, Animal ; Fatty Acids, Volatile/blood/*metabolism ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; Kidney/physiopathology ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Renal Insufficiency, Chronic/*etiology/metabolism/pathology/physiopathology ; }, abstract = {Chronic kidney disease (CKD) affects 10-15% of the population worldwide, results in high morbidity and mortality, and requires costly treatment and renal replacement therapy. Glomerulosclerosis, tubulointerstitial fibrosis, and persistent intestinal flora disturbance are common in CKD. Short-chain fatty acids (SCFAs), produced by the intestinal microbiota, have been previously reported to ameliorate kidney injury; however, the specific concentrations and types that are required to improve renal function remain unknown. The present study aims to evaluate the levels of SCFAs in healthy and CKD patients, and to test the hypothesis that SCFAs play a critical role in delaying CKD progression. One hundred and twenty-seven patients with CKD and 63 healthy controls from China were enrolled in the present study. Butyrate, which is considered beneficial to humans, was almost three-times higher in healthy volunteers than that in CKD5 subjects (P=0.001). Moreover, the serum SCFA levels in controls were significantly higher than that in CKD patients (P<0.05), and the butyrate level among CKD5 patients (1.48 ± 0.60 μmol/l) was less than half of that in controls (3.44 ± 2.12 μmol/l, P<0.001). In addition, we observed an inverse correlation between butyrate level and renal function (P<0.05). A CKD rat model transplanted with microbiota obtained from CKD patients exhibited accelerated CKD progression via increased production of trimethylamine N-oxide (TMAO), which was reversed by supplementation with extra butyrate. Our results showed that SCFA levels were reduced in CKD patients and that butyrate supplementation might delay CKD progression.}, }
@article {pmid31465241, year = {2019}, author = {Liu, Z and Li, N and Fang, H and Chen, X and Guo, Y and Gong, S and Niu, M and Zhou, H and Jiang, Y and Chang, P and Chen, P}, title = {Enteric dysbiosis is associated with sepsis in patients.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {11}, pages = {12299-12310}, pmid = {31465241}, issn = {1530-6860}, mesh = {Animals ; Dysbiosis/*complications ; Gastrointestinal Microbiome/*physiology ; Humans ; Lipid Metabolism ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Sepsis/*etiology ; }, abstract = {Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to microbial infection. For decades, the potential role of gut microbiota in sepsis pathogenesis has been revealed. However, the systemic and functional link between gut microbiota and sepsis has remained unexplored. To address this gap in knowledge, we carried out systematic analyses on clinical stool samples from patients with sepsis, including 16S rDNA sequencing, metabolomics, and metaproteomics analyses. In addition, we performed fecal microbiota transplantation from human to mice to validate the roles of gut microbiota on sepsis progression. We found that the composition of gut microbiota was significantly disrupted in patients with sepsis compared with healthy individuals. Besides, the microbial functions were significantly altered in septic feces as identified by metabolomics and metaproteomics analyses. Interestingly, mice that received septic feces exhibited more severe hepatic inflammation and injury than mice that received healthy feces after cecal ligation and puncture. Finally, several strains of intestinal microbiota and microbial metabolites were corelated with serum total bilirubin levels in patients with sepsis. Taken together, our data indicated that sepsis development is associated with the disruption of gut microbiota at both compositional and functional levels, and such enteric dysbiosis could promote organ inflammation and injury during sepsis.-Liu, Z., Li, N., Fang, H., Chen, X., Guo, Y., Gong, S., Niu, M., Zhou, H., Jiang, Y., Chang, P., Chen, P. Enteric dysbiosis is associated with sepsis in patients.}, }
@article {pmid31462301, year = {2019}, author = {Zhong, S and Zeng, J and Deng, Z and Jiang, L and Zhang, B and Yang, K and Wang, W and Zhang, T}, title = {Fecal microbiota transplantation for refractory diarrhea in immunocompromised diseases: a pediatric case report.}, journal = {Italian journal of pediatrics}, volume = {45}, number = {1}, pages = {116}, pmid = {31462301}, issn = {1824-7288}, mesh = {Child, Preschool ; Diarrhea/*etiology/*therapy ; *Fecal Microbiota Transplantation ; Humans ; *Immunocompromised Host ; Male ; }, abstract = {BACKGROUND: Immunocompromised (IC) patients have an increased risk of refractory diarrhea. Fecal microbiota transplantation (FMT) is a safe and effective therapy for infection-related diarrhea which are mainly mediated by the loss of the microbial colonization, although there is concern that IC patients may be at higher risk of infectious complications related to FMT. And reports of FMT in IC children are limited.<br><br>CASE PRESENTATION: We describe two cases of FMT in IC children with refractory diarrhea. One IC child had polyendocrinopathy, enteropathy, X-linked syndrome and the other child had graft-versus-host disease. Both of the children had a long course of diarrhea and no response to traditional treatment. FMT was performed on both patients via nasojejunal tubes under guidance of gastroduodenoscopy. After FMT, the patients achieved remission of symptoms and neither of them had related infectious complications. Microbiota analysis showed that FMT resulted in reconstruction of a diverse microbiota.<br><br>CONCLUSIONS: Use of FMT is safe and effective in treatment of refractory diarrhea in IC children with a damaged microbiota.}, }
@article {pmid31460793, year = {2019}, author = {Camilleri, M}, title = {What's in the pipeline for lower functional gastrointestinal disorders in the next 5 years?.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {317}, number = {5}, pages = {G640-G650}, pmid = {31460793}, issn = {1522-1547}, support = {R01 DK067071/DK/NIDDK NIH HHS/United States ; R01 DK115950/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Constipation/*metabolism/microbiology/physiopathology/therapy ; Diarrhea/*metabolism/microbiology/physiopathology/therapy ; Gastrointestinal Microbiome ; Gastrointestinal Transit ; Humans ; Intestinal Absorption ; }, abstract = {The overall objectives of this review are to summarize actionable biomarkers for organic etiology of lower functional gastrointestinal disorders (FGIDs) that lead to individualized treatment for their FGIDs and to assess the pipeline for novel approaches to the management of constipation, diarrhea, and chronic abdominal pain in lower FGIDs. The new approaches to therapy include ion exchangers/transporters for functional constipation (sodium-glucose cotransporter 1, Na[+]/H[+] exchanger 3, and solute carrier family 26 member 3 inhibitors), bile acid modulators for constipation such as ileal bile acid transporter inhibitors and fibroblast growth factor 19 analog for functional constipation, and bile acid sequestrants or farnesoid X receptor agonists for functional diarrhea. Treatment for chronic abdominal pain remains an unmet need in patients with lower FGIDs, and promising novel approaches include delayed-release linaclotide, nonclassical opioid visceral analgesics, and selective cannabinoid receptor agonists. The role of probiotics, fecal microbial transplantation, and possible future microbiome therapies is discussed.}, }
@article {pmid31456808, year = {2019}, author = {Fiedorová, K and Radvanský, M and Bosák, J and Grombiříková, H and Němcová, E and Králíčková, P and Černochová, M and Kotásková, I and Lexa, M and Litzman, J and Šmajs, D and Freiberger, T}, title = {Bacterial but Not Fungal Gut Microbiota Alterations Are Associated With Common Variable Immunodeficiency (CVID) Phenotype.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {1914}, pmid = {31456808}, issn = {1664-3224}, mesh = {Adult ; Aged ; Bacteria/classification/genetics/*immunology ; Biodiversity ; Case-Control Studies ; Common Variable Immunodeficiency/immunology/*microbiology ; Family Health ; Feces/microbiology ; Female ; Fungi/classification/genetics/*immunology ; *Gastrointestinal Microbiome/immunology ; Health Status ; Humans ; Immunoglobulin A/blood/immunology ; Male ; Middle Aged ; *Mycobiome ; }, abstract = {Common Variable Immunodeficiency (CVID) is the most frequent symptomatic immune disorder characterized by reduced serum immunoglobulins. Patients often suffer from infectious and serious non-infectious complications which impact their life tremendously. The monogenic cause has been revealed in a minority of patients so far, indicating the role of multiple genes and environmental factors in CVID etiology. Using 16S and ITS rRNA amplicon sequencing, we analyzed the bacterial and fungal gut microbiota, respectively, in a group of 55 participants constituting of CVID patients and matched healthy controls including 16 case-control pairs living in the same household, to explore possible associations between gut microbiota composition and disease phenotype. We revealed less diverse and significantly altered bacterial but not fungal gut microbiota in CVID patients, which additionally appeared to be associated with a more severe disease phenotype. The factor of sharing the same household impacted both bacterial and fungal microbiome data significantly, although not as strongly as CVID diagnosis in bacterial assessment. Overall, our results suggest that gut bacterial microbiota is altered in CVID patients and may be one of the missing environmental drivers contributing to some of the symptoms and disease severity. Paired samples serving as controls will provide a better resolution between disease-related dysbiosis and other environmental confounders in future studies.}, }
@article {pmid31456783, year = {2019}, author = {Chong, PP and Chin, VK and Looi, CY and Wong, WF and Madhavan, P and Yong, VC}, title = {Corrigendum: The Microbiome and Irritable Bowel Syndrome - A Review on the Pathophysiology, Current Research and Future Therapy.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1870}, doi = {10.3389/fmicb.2019.01870}, pmid = {31456783}, issn = {1664-302X}, abstract = {[This corrects the article DOI: 10.3389/fmicb.2019.01136.].}, }
@article {pmid31456544, year = {2019}, author = {Fredericks, E and Hoosien, E and Brink, A}, title = {The case for stool banks in South Africa.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {109}, number = {8}, pages = {546-547}, doi = {10.7196/SAMJ.2019.v109i8.14169}, pmid = {31456544}, issn = {2078-5135}, mesh = {*Biological Specimen Banks ; Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Humans ; South Africa ; Tissue and Organ Procurement/standards ; }, }
@article {pmid31455805, year = {2019}, author = {Bo, TB and Zhang, XY and Wen, J and Deng, K and Qin, XW and Wang, DH}, title = {The microbiota-gut-brain interaction in regulating host metabolic adaptation to cold in male Brandt's voles (Lasiopodomys brandtii).}, journal = {The ISME journal}, volume = {13}, number = {12}, pages = {3037-3053}, pmid = {31455805}, issn = {1751-7370}, mesh = {Acclimatization ; Adaptation, Physiological ; Animals ; Arvicolinae/*microbiology/*physiology ; Bacteria/genetics/isolation &amp; purification/metabolism ; Brain/*metabolism ; Cecum/metabolism/microbiology ; Cold Temperature ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Ghrelin/metabolism ; Male ; Neurotransmitter Agents/metabolism ; Norepinephrine/metabolism ; Thermogenesis ; }, abstract = {Gut microbiota play a critical role in orchestrating metabolic homeostasis of the host. However, the crosstalk between host and microbial symbionts in small mammals are rarely illustrated. We used male Brandt's voles (Lasiopodomys brandtii) to test the hypothesis that gut microbiota and host neurotransmitters, such as norepinephrine (NE), interact to regulate energetics and thermogenesis during cold acclimation. We found that increases in food intake and thermogenesis were associated with increased monoamine neurotransmitters, ghrelin, short-chain fatty acids, and altered cecal microbiota during cold acclimation. Further, our pair-fed study showed that cold temperature can alter the cecal microbiota independently of overfeeding. Using cecal microbiota transplant along with β3-adrenoceptor antagonism and PKA inhibition, we confirmed that transplant of cold-acclimated microbiota increased thermogenesis through activation of cAMP-PKA-pCREB signaling. In addition, NE manipulation induced a long-term alteration in gut microbiota structure. These data demonstrate that gut microbiota-NE crosstalk via cAMP signaling regulates energetics and thermogenesis during cold acclimation in male Brandt's voles.}, }
@article {pmid31448542, year = {2020}, author = {Brüssow, H}, title = {Problems with the concept of gut microbiota dysbiosis.}, journal = {Microbial biotechnology}, volume = {13}, number = {2}, pages = {423-434}, pmid = {31448542}, issn = {1751-7915}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Symbiosis ; }, abstract = {The human microbiome research is with the notable exception of fecal transplantation still mostly in a descriptive phase. Part of the difficulty for translating research into medical interventions is due to the large compositional complexity of the microbiome resulting in datasets that need sophisticated statistical methods for their analysis and do not lend to industrial applications. Another part of the difficulty might be due to logical flaws in terminology particularly concerning 'dysbiosis' that avoids circular conclusions and is based on sound ecological and evolutionary reasoning. Many case-control studies are underpowered necessitating more meta-analyses that sort out consistent from spurious dysbiosis-disease associations. We also need for the microbiome a transition from statistical associations to causal relationships with diseases that fulfil a set of modified Koch's postulates for commensals. Disturbingly, the most sophisticated statistical analyses explain only a small percentage of the variance in the microbiome. Microbe-microbe interactions irrelevant to the host and stochastic processes might play a greater role than anticipated. To satisfy the concept of Karl Popper about conjectures and refutations in the scientific process, we should also conduct more experiments that try to refute the role of the commensal gut microbiota for human health and disease.}, }
@article {pmid31443761, year = {2019}, author = {Monif, GRG}, title = {Is ulcerative colitis a disease of a dysfunctional microbiota?.}, journal = {Medical hypotheses}, volume = {131}, number = {}, pages = {109300}, doi = {10.1016/j.mehy.2019.109300}, pmid = {31443761}, issn = {1532-2777}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Anti-Bacterial Agents/adverse effects/therapeutic use ; Biological Products/therapeutic use ; Colitis, Ulcerative/classification/diet therapy/*microbiology/therapy ; Combined Modality Therapy ; Enema ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Humans ; }, abstract = {Using the gross pathology literature and the prior decoupling of Crohn's disease from inflammatory bowel disease, IDI's White Paper puts into question the current understanding of what ulcerative colitis is and how it can be therapeutically addressed. The pathology literature, when coupled with the ability of fecal enema therapy to achieve a remission rate significantly superior to those documented for biologics, puts focus on the dominant role of the gastrointestinal microbiota in both disease induction and its recovery. The concept of endogenous enterotoxogenesis is introduced.}, }
@article {pmid31440436, year = {2019}, author = {Hasan, N and Yang, H}, title = {Factors affecting the composition of the gut microbiota, and its modulation.}, journal = {PeerJ}, volume = {7}, number = {}, pages = {e7502}, pmid = {31440436}, issn = {2167-8359}, abstract = {Gut microbiota have important functions in the body, and imbalances in the composition and diversity of those microbiota can cause several diseases. The host fosters favorable microbiota by releasing specific factors, such as microRNAs, and nonspecific factors, such as antimicrobial peptides, mucus and immunoglobulin A that encourage the growth of specific types of bacteria and inhibit the growth of others. Diet, antibiotics, and age can change gut microbiota, and many studies have shown the relationship between disorders of the microbiota and several diseases and reported some ways to modulate that balance. In this review, we highlight how the host shapes its gut microbiota via specific and nonspecific factors, how environmental and nutritional factors affect it, and how to modulate it using prebiotics, probiotics, and fecal microbiota transplantation.}, }
@article {pmid31439276, year = {2019}, author = {Li, J and Hu, FB}, title = {Research digest: reshaping the gut microbiota.}, journal = {The lancet. Diabetes &amp; endocrinology}, volume = {7}, number = {9}, pages = {671}, doi = {10.1016/S2213-8587(19)30270-0}, pmid = {31439276}, issn = {2213-8595}, mesh = {Biomedical Research ; Dysbiosis/*microbiology/physiopathology ; Fecal Microbiota Transplantation/trends ; Feces/*microbiology ; Gastrointestinal Microbiome/immunology/*physiology ; Humans ; Immune System Diseases/*microbiology ; Inflammation/immunology/*microbiology ; Mental Disorders/*microbiology ; Metabolic Diseases/*microbiology ; Nutritional Physiological Phenomena ; }, }
@article {pmid31439031, year = {2019}, author = {Zhang, Y and Huang, R and Cheng, M and Wang, L and Chao, J and Li, J and Zheng, P and Xie, P and Zhang, Z and Yao, H}, title = {Gut microbiota from NLRP3-deficient mice ameliorates depressive-like behaviors by regulating astrocyte dysfunction via circHIPK2.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {116}, pmid = {31439031}, issn = {2049-2618}, mesh = {Animals ; Astrocytes/cytology/*metabolism ; Behavior, Animal/*physiology ; Depression/microbiology/pathology/*therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism ; Protein Serine-Threonine Kinases/metabolism ; }, abstract = {BACKGROUND: Inflammasomes have been found to interact with the gut microbiota, and this effect is associated with depression, but the mechanisms underlying this interaction have not been elucidated in detail.<br><br>RESULTS: The locomotor activity of NLRP3 KO mice was significantly greater than that of their WT littermates, while cohousing and transplantation of the NLRP3 KO gut microbiota avoid the effects of NLRP3 KO on the general locomotor activity at baseline. Meanwhile, transplantation of the NLRP3 KO microbiota alleviated the CUS-induced depressive-like behaviors. The compositions of the gut microbiota in NLRP3 KO mice and WT mice were significantly different in terms of the relative abundance of Firmicutes, Proteobacteria, and Bacteroidetes. Fecal microbiota transplantation (FMT) from NLRP3 KO mice significantly ameliorated the depressive-like behavior induced by chronic unpredictable stress (CUS) in recipient mice. Given the correlation between circular RNA HIPK2 (circHIPK2) and depression and the observation that the level of circHIPK2 expression was significantly increased in CUS-treated mice compared with that in the control group, further experiments were performed. FMT significantly ameliorated astrocyte dysfunction in recipient mice treated with CUS via inhibition of circHIPK2 expression.<br><br>CONCLUSIONS: Our study illustrates the involvement of the gut microbiota-circHIPK2-astrocyte axis in depression, providing translational evidence that transplantation of the gut microbiota from NLRP3 KO mice may serve as a novel therapeutic strategy for depression.}, }
@article {pmid31436833, year = {2020}, author = {Galloway-Peña, JR and Shi, Y and Peterson, CB and Sahasrabhojane, P and Gopalakrishnan, V and Brumlow, CE and Daver, NG and Alfayez, M and Boddu, PC and Khan, MAW and Wargo, JA and Do, KA and Jenq, RR and Kontoyiannis, DP and Shelburne, SA}, title = {Gut Microbiome Signatures Are Predictive of Infectious Risk Following Induction Therapy for Acute Myeloid Leukemia.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {71}, number = {1}, pages = {63-71}, pmid = {31436833}, issn = {1537-6591}, support = {K01 AI143881/AI/NIAID NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA219896/CA/NCI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Feces ; *Gastrointestinal Microbiome ; Humans ; Induction Chemotherapy ; *Leukemia, Myeloid, Acute/drug therapy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The majority of studies that provide insights into the influence of the microbiome on the health of hematologic malignancy patients have concentrated on the transplant setting. Here, we sought to assess the predictive capacity of the gastrointestinal microbiome and its relationship to infectious outcomes in patients with acute myeloid leukemia (AML).<br><br>METHODS: 16s rRNA-based analysis was performed on oral swabs and stool samples obtained biweekly from baseline until neutrophil recovery following induction chemotherapy (IC) in 97 AML patients. Microbiome characteristics were correlated with clinical outcomes both during and after IC completion.<br><br>RESULTS: At the start of IC, higher stool Shannon diversity (hazard ratio [HR], 0.36; 95% confidence interval [CI], .18-.74) and higher relative abundance of Porphyromonadaceae (HR, 0.36; 95% CI, .18-.73) were associated with increased probability of remaining infection-free during neutropenia. A baseline stool Shannon diversity cutoff of <2 had optimal operating characteristics for predicting infectious complications during neutropenia. Although 56 patients received therapy >72 hours with a carbapenem, none of the patients had an infection with an extended spectrum &#x3b2;-lactamase-producing organism. Patients who received carbapenems for >72 hours had significantly lower &#x3b1;-diversity at neutrophil recovery (P = .001) and were approximately 4 times more likely to have infection in the 90 days following neutrophil recovery (HR, 4.55; 95% CI, 1.73-11.93).<br><br>CONCLUSIONS: Our results suggest that gut microbiome evaluation could assist with infectious risk stratification and that improved targeting of antibiotic administration during IC could decrease subsequent infectious complications in AML patients.Baseline microbiome diversity is a strong independent predictor of infection during acute myeloid leukemia induction chemotherapy (IC) among clinical and microbiome covariates. Higher baseline levels of Porphyromonadaceae appear protective against infection, while carbapenem use is associated with consequences to the microbiome and infection susceptibility post-IC.}, }
@article {pmid31435014, year = {2019}, author = {Kim, SG and Becattini, S and Moody, TU and Shliaha, PV and Littmann, ER and Seok, R and Gjonbalaj, M and Eaton, V and Fontana, E and Amoretti, L and Wright, R and Caballero, S and Wang, ZX and Jung, HJ and Morjaria, SM and Leiner, IM and Qin, W and Ramos, RJJF and Cross, JR and Narushima, S and Honda, K and Peled, JU and Hendrickson, RC and Taur, Y and van den Brink, MRM and Pamer, EG}, title = {Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus.}, journal = {Nature}, volume = {572}, number = {7771}, pages = {665-669}, pmid = {31435014}, issn = {1476-4687}, support = {U01 AI124275/AI/NIAID NIH HHS/United States ; T34 GM007823/GM/NIGMS NIH HHS/United States ; S10 OD010598/OD/NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; T32 GM007739/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/biosynthesis/isolation &amp; purification/metabolism/pharmacology ; Bacteriocins/genetics/isolation &amp; purification/*metabolism/*pharmacology ; Enterococcus faecium/*drug effects/growth &amp; development/isolation &amp; purification ; Feces/microbiology ; Female ; Gastrointestinal Tract/drug effects/microbiology ; Germ-Free Life ; Gram-Positive Bacteria/drug effects/growth &amp; development ; Humans ; Lactococcus lactis/chemistry/growth &amp; development/*metabolism/physiology ; Mice ; Microbial Sensitivity Tests ; Microbiota/genetics ; Nisin/chemistry/pharmacology ; *Probiotics ; Symbiosis/drug effects ; Vancomycin/pharmacology ; Vancomycin Resistance/*drug effects ; Vancomycin-Resistant Enterococci/*drug effects/growth &amp; development/isolation &amp; purification ; }, abstract = {Intestinal commensal bacteria can inhibit dense colonization of the gut by vancomycin-resistant Enterococcus faecium (VRE), a leading cause of hospital-acquired infections[1,2]. A four-strained consortium of commensal bacteria that contains Blautia producta BPSCSK can reverse antibiotic-induced susceptibility to VRE infection[3]. Here we show that BPSCSK reduces growth of VRE by secreting a lantibiotic that is similar to the nisin-A produced by Lactococcus lactis. Although the growth of VRE is inhibited by BPSCSK and L. lactis in vitro, only BPSCSK colonizes the colon and reduces VRE density in vivo. In comparison to nisin-A, the BPSCSK lantibiotic has reduced activity against intestinal commensal bacteria. In patients at high risk of VRE infection, high abundance of the lantibiotic gene is associated with reduced density of E. faecium. In germ-free mice transplanted with patient-derived faeces, resistance to VRE colonization correlates with abundance of the lantibiotic gene. Lantibiotic-producing commensal strains of the gastrointestinal tract reduce colonization by VRE and represent potential probiotic agents to re-establish resistance to VRE.}, }
@article {pmid31434991, year = {2020}, author = {Wu, M and Liu, J and Li, F and Huang, S and He, J and Xue, Y and Fu, T and Feng, S and Li, Z}, title = {Antibiotic-induced dysbiosis of gut microbiota impairs corneal development in postnatal mice by affecting CCR2 negative macrophage distribution.}, journal = {Mucosal immunology}, volume = {13}, number = {1}, pages = {47-63}, pmid = {31434991}, issn = {1935-3456}, mesh = {Animals ; Animals, Newborn ; Anti-Bacterial Agents/*adverse effects/therapeutic use ; Cell Movement ; Cells, Cultured ; Cornea/*physiology ; Drug-Related Side Effects and Adverse Reactions/*immunology ; Dysbiosis/etiology/*immunology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Macrophages/*immunology ; Mice ; Mice, Inbred C57BL ; Postnatal Care ; RNA, Ribosomal, 16S/*genetics ; Receptors, CCR2/metabolism ; }, abstract = {Antibiotics are extremely useful, but they can cause adverse impacts on host bodies. We found that antibiotic treatment altered the composition of the gut microbiota and the gene expression profile in the corneal tissues of postnatal mice and decreased the corneal size and thickness, the angiogenesis of limbal blood vessels, and the neurogenesis of corneal nerve fibers. The reconstitution of the gut microbiota with fecal transplants in antibiotic-treated mice largely reversed these impairments in corneal development. Furthermore, C-C chemokine receptor type 2 negative (CCR2[-]) macrophages were confirmed to participate in corneal development, and their distribution in the cornea was regulated by the gut microbiota. We propose that the CCR2[-] macrophage population is a crucial mediator through which gut microbiota affect corneal development in postnatal mice. In addition, probiotics were shown to have the potential effect of restoring corneal development in antibiotic-treated mice. Abx-induced gut dysbiosis has significant, long-term effects on the development of the cornea, and reversal of these suppressive effects takes a long time.}, }
@article {pmid31434568, year = {2019}, author = {Chang, CS and Kao, CY}, title = {Current understanding of the gut microbiota shaping mechanisms.}, journal = {Journal of biomedical science}, volume = {26}, number = {1}, pages = {59}, pmid = {31434568}, issn = {1423-0127}, support = {IM-107-PP-04//National Health Research Institutes/ ; 104-2320-B-400-019-MY3//Ministry of Science and Technology, Taiwan/ ; 106-2628-B-400-001-MY3//Ministry of Science and Technology, Taiwan/ ; 108-2321-B-400-011-//Ministry of Science and Technology, Taiwan/ ; }, mesh = {Antimicrobial Cationic Peptides/*physiology ; Epithelium/*physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; *Immunity, Innate ; Immunoglobulin A, Secretory/*physiology ; MicroRNAs/physiology ; Microvilli/physiology ; Mucus/*physiology ; Tight Junctions/physiology ; }, abstract = {Increasing evidences have shown strong associations between gut microbiota and many human diseases, and understanding the dynamic crosstalks of host-microbe interaction in the gut has become necessary for the detection, prevention, or therapy of diseases. Many reports have showed that diet, nutrient, pharmacologic factors and many other stimuli play dominant roles in the modulation of gut microbial compositions. However, it is inappropriate to neglect the impact of host factors on shaping the gut microbiota. In this review, we highlighted the current findings of the host factors that could modulate the gut microbiota. Particularly the epithelium-associated factors, including the innate immune sensors, anti-microbial peptides, mucus barrier, secretory IgAs, epithelial microvilli, epithelial tight junctions, epithelium metabolism, oxygen barrier, and even the microRNAs are discussed in the context of the microbiota shaping. With these shaping factors, the gut epithelial cells could select the residing microbes and affect the microbial composition. This knowledge not only could provide the opportunities to better control many diseases, but may also be used for predicting the success of fecal microbiota transplantation clinically.}, }
@article {pmid31431719, year = {2019}, author = {Staffas, A and van den Brink, M}, title = {The intestinal flora is required for post-transplant hematopoiesis in recipients of a hematopoietic stem cell transplantation.}, journal = {Bone marrow transplantation}, volume = {54}, number = {Suppl 2}, pages = {756-758}, pmid = {31431719}, issn = {1476-5365}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Gastrointestinal Microbiome/*physiology ; Hematopoiesis/*physiology ; Hematopoietic Stem Cell Transplantation/*methods ; Humans ; Mice ; Transplantation Conditioning/*methods ; }, abstract = {Recent studies in both mice and humans have demonstrated that the intestinal microbiota can affect hematopoiesis. Here, we performed experiments in preclinical mouse models for syngeneic and allogeneic HCT. To study the metabolic effects of intestinal flora depletion on post-transplant hematopoiesis in humans, we performed HCT experiments using a metabolic chamber and bomb calorimetry of feces. Taken together, we show that the intestinal microbiota supports post-transplant hematopoietic reconstitution in HCT recipients through its role in dietary energy uptake.}, }
@article {pmid31431428, year = {2019}, author = {Guery, B and Galperine, T and Barbut, F}, title = {Clostridioides difficile: diagnosis and treatments.}, journal = {BMJ (Clinical research ed.)}, volume = {366}, number = {}, pages = {l4609}, doi = {10.1136/bmj.l4609}, pmid = {31431428}, issn = {1756-1833}, mesh = {Algorithms ; Anti-Bacterial Agents/therapeutic use ; Bacterial Vaccines ; Biomarkers/analysis ; Clostridioides difficile/immunology/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/*diagnosis/epidemiology/*therapy ; Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Recurrence ; }, abstract = {Clostridioides difficile (formerly Clostridium) is a major cause of healthcare associated diarrhea, and is increasingly present in the community. Historically, C difficile infection was considered easy to diagnose and treat. Over the past two decades, however, diagnostic techniques have changed in line with a greater understanding of the physiopathology of C difficile infection and the use of new therapeutic molecules. The evolution of diagnosis showed there was an important under- and misdiagnosis of C difficile infection, emphasizing the importance of algorithms recommended by European and North American infectious diseases societies to obtain a reliable diagnosis. Previously, metronidazole was considered the reference drug to treat C difficile infection, but more recently vancomycin and other newer drugs are shown to have higher cure rates. Recurrence of infection represents a key parameter in the evaluation of new drugs, and the challenge is to target the right population with the adapted therapeutic molecule. In multiple recurrences, fecal microbiota transplantation is recommended. New approaches, including antibodies, vaccines, and new molecules are already available or in the pipeline, but more data are needed to support the inclusion of these in practice guidelines. This review aims to provide a baseline for clinicians to understand and stratify their choice in the diagnosis and treatment of C difficile infection based on the most recent data available.}, }
@article {pmid31429939, year = {2019}, author = {Castro, LRP and Calvet, FC and Sousa, KL and Silva, VP and Lobo, PS and Penha, ET and Guerra, SFS and Bezerra, DAM and Mascarenhas, JDP and Pinheiro, HHC and Costa, IB and Resque, HR and Soares, LS}, title = {Prevalence of rotavirus and human bocavirus in immunosuppressed individuals after renal transplantation in the Northern Region of Brazil.}, journal = {Journal of medical virology}, volume = {91}, number = {12}, pages = {2125-2133}, doi = {10.1002/jmv.25569}, pmid = {31429939}, issn = {1096-9071}, mesh = {Adult ; Brazil/epidemiology ; Coinfection/epidemiology/virology ; Feces/*virology ; Female ; Genotype ; Human bocavirus/genetics/*isolation &amp; purification ; Humans ; *Immunocompromised Host ; Kidney Transplantation/*adverse effects ; Longitudinal Studies ; Male ; Parvoviridae Infections/epidemiology/virology ; Phylogeny ; Prevalence ; Rotavirus/genetics/*isolation &amp; purification ; Rotavirus Infections/epidemiology/virology ; Sequence Analysis, DNA ; Transplant Recipients/statistics &amp; numerical data ; }, abstract = {Immunosuppressive therapy causes severe impairment of host defense and diarrhea is a frequent complication in renal transplant recipients. This study aimed to describe the occurrence of Rotavirus A (RVA) and Human Bocavirus (HBoV) in fecal samples of immunosuppressed patients submitted to renal transplantation during posttransplant follow-up. A longitudinal study was carried out involving a 25-patient cohort, selected for kidney transplantation. A total of 126 fecal samples were collected between May 2014 and May 2016. Molecular techniques were used to detect and characterize circulating RVA and HBoV genotypes and statistical analysis were applied to verify the association between epidemiological and clinical characteristics. The prevalence of RVA and HBoV was 24% (6/25) and 40% (10/25), respectively. Among RVA and HBoV positive cases, the majority was female; did not conduct water treatment nor had adequate sewage facilities. The most detected genotypes were RVA G3 (62.5%) and HBoV-3 (95%). Phylogenetic analysis of HBoV strains indicated that studied samples were similar to those found in Asian and American countries. The present study point out the circulation of these viral agents among immunosuppressed individuals and these findings will enable the construction of new knowledge and care perspectives on the cause of diarrhea in this population.}, }
@article {pmid31429237, year = {2019}, author = {Frøland, SS}, title = {[Fecal transplantation and the microbiome].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {139}, number = {11}, pages = {}, doi = {10.4045/tidsskr.19.0445}, pmid = {31429237}, issn = {0807-7096}, mesh = {Fecal Microbiota Transplantation/*classification ; Humans ; Norway ; Terminology as Topic ; *Translations ; }, }
@article {pmid31429236, year = {2019}, author = {Juul, FE and Valeur, J}, title = {[F. E. Juul and J. Valeur respond].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {139}, number = {11}, pages = {}, doi = {10.4045/tidsskr.19.0446}, pmid = {31429236}, issn = {0807-7096}, mesh = {*Electronic Nicotine Delivery Systems ; Fecal Microbiota Transplantation ; *Microbiota ; *Social Media ; }, }
@article {pmid31427714, year = {2019}, author = {Horvath, A and Rainer, F and Bashir, M and Leber, B and Schmerboeck, B and Klymiuk, I and Groselj-Strele, A and Durdevic, M and Freedberg, DE and Abrams, JA and Fickert, P and Stiegler, P and Stadlbauer, V}, title = {Biomarkers for oralization during long-term proton pump inhibitor therapy predict survival in cirrhosis.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {12000}, pmid = {31427714}, issn = {2045-2322}, mesh = {Aged ; *Biomarkers ; Dysbiosis/drug therapy ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/drug effects ; Humans ; Intestinal Mucosa/drug effects/metabolism/microbiology ; Liver Cirrhosis/*complications/etiology/*mortality ; Male ; Middle Aged ; Mortality ; Prognosis ; Proportional Hazards Models ; Proton Pump Inhibitors/administration &amp; dosage/*adverse effects ; Treatment Outcome ; }, abstract = {Proton pump inhibitors (PPI) are an invaluable therapy option for acid related diseases; however, PPI therapy is also linked to a series of side effects in cirrhosis, such as microbiome alterations, spontaneous bacterial peritonitis and hepatic encephalopathy. Decision tools to balance benefits and risks of PPI therapy are largely missing. In this study, we tested gut-derived biomarkers to identify PPI-associated dysbiosis, its association with gut barrier function and liver-related mortality. In this observational study, faecal microbiome composition data obtained from 16S rDNA sequencing of 90 cirrhotic patients with and without long-term PPI use and additional potential biomarkers identified from the literature were evaluated for their predictive value regarding PPI-associated dysbiosis and liver-related three-year mortality. In addition, faecal calprotectin, faecal zonulin and serum lipopolysaccharides were assessed as markers for intestinal inflammation, gut permeability and bacterial translocation. Streptococcus salivarius, Veillonella parvula and the genus Streptococcus were significantly increased in patients with long-term PPI therapy and performed well as biomarkers for PPI-associated dysbiosis (accuracy: 74%, 72% and 74%, respectively). The abundance of Streptococcus salivarius was linked to intestinal inflammation and gut barrier dysfunction, whereas the abundance of Veillonella parvula showed associations with liver disease severity; both were independent predictors for liver-related three-year mortality. Gut-derived biomarkers of PPI-associated dysbiosis are linked to worse outcome and a potential option to evaluate the risks of adverse events during long-term PPI therapy.}, }
@article {pmid31425750, year = {2019}, author = {Chen, R and Xu, Y and Wu, P and Zhou, H and Lasanajak, Y and Fang, Y and Tang, L and Ye, L and Li, X and Cai, Z and Zhao, J}, title = {Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota.}, journal = {Pharmacological research}, volume = {148}, number = {}, pages = {104403}, doi = {10.1016/j.phrs.2019.104403}, pmid = {31425750}, issn = {1096-1186}, mesh = {Animals ; Brain Ischemia/*microbiology/*therapy ; Butyric Acid/*pharmacology ; Fatty Acids, Volatile/*pharmacology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Lactobacillus/physiology ; Male ; Microbiota/physiology ; Rats ; Rats, Sprague-Dawley ; Stroke/*microbiology/*therapy ; }, abstract = {The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, we aimed to clarify the mechanism by which gut microbiota and SCFAs can treat cerebral ischemic stroke in rat middle cerebral artery occlusion models and use the information to develop new therapies. Our results show that oral administration of non-absorbable antibiotics reduced neurological impairment and the cerebral infarct volume, relieved cerebral edemas, and decreased blood lipid levels by altering the gut microbiota. We also found that ischemic stroke decreased intestinal levels of SCFAs. And that transplanting fecal microbiota rich in these metabolites was an effective means of treating the condition. Compared with other SCFAs, butyric acid showed the highest negative correlation with ischemic stroke. Supplementation with butyric acid treated models of ischemic stroke effectively by remodeling the gut microbiota, enriching the beneficial Lactobacillus, and repairing the leaky gut. In conclusion, interfering with the gut microbiota by transplanting fecal bacteria rich in SCFAs and supplementing with butyric acid were found to be effective treatments for cerebral ischemic stroke.}, }
@article {pmid31423842, year = {2019}, author = {Butts, E and Padala, SA and Vakiti, A and Kota, V}, title = {Rectovaginal Fistula as a Complication of Fecal Management System.}, journal = {Journal of investigative medicine high impact case reports}, volume = {7}, number = {}, pages = {2324709619869368}, pmid = {31423842}, issn = {2324-7096}, mesh = {Adolescent ; Catheterization/adverse effects ; Catheters/*adverse effects ; Fatal Outcome ; Female ; Graft Rejection/complications ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Multiple Organ Failure/etiology/therapy ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/complications/therapy ; Rectovaginal Fistula/*etiology ; *Rectum ; }, abstract = {We report a rare complication of the use of an intrarectal catheter. An 18-year-old female with T-cell acute lymphoblastic leukemia post-matched unrelated donor allogeneic stem cell transplantation (auto-SCT) developed hepatic encephalopathy secondary to hepatic sinusoidal obstructive disease. A fecal management system was used to contain and divert fecal matter in this immobilized patient. Approximately 1 month after placement of an intrarectal catheter, stool was noted in the vaginal vault. Speculum examination confirmed development of a rectovaginal fistula.}, }
@article {pmid31419514, year = {2019}, author = {Mouries, J and Brescia, P and Silvestri, A and Spadoni, I and Sorribas, M and Wiest, R and Mileti, E and Galbiati, M and Invernizzi, P and Adorini, L and Penna, G and Rescigno, M}, title = {Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development.}, journal = {Journal of hepatology}, volume = {71}, number = {6}, pages = {1216-1228}, pmid = {31419514}, issn = {1600-0641}, mesh = {Animals ; Bacterial Translocation/*drug effects ; *Capillary Permeability/drug effects/physiology ; Chenodeoxycholic Acid/*analogs &amp; derivatives/pharmacology ; Diet, High-Fat ; Disease Models, Animal ; Dysbiosis/immunology ; Gastrointestinal Microbiome/*physiology ; Inflammation/metabolism ; Insulin Resistance ; *Intestinal Mucosa/drug effects/metabolism/microbiology ; Liver/pathology ; Mice ; *Non-alcoholic Fatty Liver Disease/immunology/metabolism/therapy ; Protective Agents/pharmacology ; }, abstract = {BACKGROUND &amp; AIMS: Fatty liver disease, including non-alcoholic fatty liver (NAFLD) and steatohepatitis (NASH), has been associated with increased intestinal barrier permeability and translocation of bacteria or bacterial products into the blood circulation. In this study, we aimed to unravel the role of both intestinal barrier integrity and microbiota in NAFLD/NASH development.<br><br>METHODS: C57BL/6J mice were fed with high-fat diet (HFD) or methionine-choline-deficient diet for 1&#x202f;week or longer to recapitulate aspects of NASH (steatosis, inflammation, insulin resistance). Genetic and pharmacological strategies were then used to modulate intestinal barrier integrity.<br><br>RESULTS: We show that disruption of the intestinal epithelial barrier and gut vascular barrier (GVB) are early events in NASH pathogenesis. Mice fed HFD for only 1&#x202f;week undergo a diet-induced dysbiosis that drives GVB damage and bacterial translocation into the liver. Fecal microbiota transplantation from HFD-fed mice into specific pathogen-free recipients induces GVB damage and epididymal adipose tissue enlargement. GVB disruption depends on interference with the WNT/&#x3b2;-catenin signaling pathway, as shown by genetic intervention driving &#x3b2;-catenin activation only in endothelial cells, preventing GVB disruption and NASH development. The bile acid analogue and farnesoid X receptor agonist obeticholic acid (OCA) drives &#x3b2;-catenin activation in endothelial cells. Accordingly, pharmacologic intervention with OCA protects against GVB disruption, both as a preventive and therapeutic agent. Importantly, we found upregulation of the GVB leakage marker in the colon of patients with NASH.<br><br>CONCLUSIONS: We have identified a new player in NASH development, the GVB, whose damage leads to bacteria or bacterial product translocation into the blood circulation. Treatment aimed at restoring &#x3b2;-catenin activation in endothelial cells, such as administration of OCA, protects against GVB damage and NASH development.<br><br>LAY SUMMARY: The incidence of fatty liver disease is reaching epidemic levels in the USA, with more than 30% of adults having NAFLD (non-alcoholic fatty liver disease), which can progress to more severe non-alcoholic steatohepatitis (NASH). Herein, we show that disruption of the intestinal epithelial barrier and gut vascular barrier are early events in the development of NASH. We show that the drug obeticholic acid protects against barrier disruption and thereby prevents the development of NASH, providing further evidence for its use in the prevention or treatment of NASH.}, }
@article {pmid31414930, year = {2019}, author = {Rosenbaum, JT}, title = {Just another crappy commentary: the future of fecal microbiota transplantation.}, journal = {Expert review of clinical immunology}, volume = {15}, number = {10}, pages = {987-989}, pmid = {31414930}, issn = {1744-8409}, support = {R01 EY029266/EY/NEI NIH HHS/United States ; }, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; }, }
@article {pmid31412603, year = {2019}, author = {Khan, I and Ullah, N and Zha, L and Bai, Y and Khan, A and Zhao, T and Che, T and Zhang, C}, title = {Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome.}, journal = {Pathogens (Basel, Switzerland)}, volume = {8}, number = {3}, pages = {}, pmid = {31412603}, issn = {2076-0817}, support = {(No. BA2016036)//Jiangsu Science and Technology Major Project/ ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic complex inflammatory gut pathological condition, examples of which include Crohn's disease (CD) and ulcerative colitis (UC), which is associated with significant morbidity. Although the etiology of IBD is unknown, gut microbiota alteration (dysbiosis) is considered a novel factor involved in the pathogenesis of IBD. The gut microbiota acts as a metabolic organ and contributes to human health by performing various physiological functions; deviation in the gut flora composition is involved in various disease pathologies, including IBD. This review aims to summarize the current knowledge of gut microbiota alteration in IBD and how this contributes to intestinal inflammation, as well as explore the potential role of gut microbiota-based treatment approaches for the prevention and treatment of IBD. The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented. In addition, gut microbiota-based therapeutic approaches have also shown good evidence of their effects in the amelioration of colitis in animal models (mice) and IBD patients, which indicates that gut flora might be a new promising therapeutic target for the treatment of IBD. However, insufficient data and confusing results from previous studies have led to a failure to define a core microbiome associated with IBD and the hidden mechanism of pathogenesis, which suggests that well-designed randomized control trials and mouse models are required for further research. In addition, a better understanding of this ecosystem will also determine the role of prebiotics and probiotics as therapeutic agents in the management of IBD.}, }
@article {pmid31411909, year = {2019}, author = {Yang, J and Yang, H}, title = {Non-antibiotic therapy for Clostridioides difficile infection: a review.}, journal = {Critical reviews in clinical laboratory sciences}, volume = {56}, number = {7}, pages = {493-509}, doi = {10.1080/10408363.2019.1648377}, pmid = {31411909}, issn = {1549-781X}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/*drug therapy/pathology ; Diet ; Fecal Microbiota Transplantation ; Humans ; Nanoparticles/chemistry ; Probiotics/therapeutic use ; }, abstract = {Clostridioides difficile infection (CDI) is a common infectious disease that is mainly caused by antibiotics. Antibiotic therapy is still the dominant treatment for CDI, although it is accompanied by side effects. Probiotics, fecal microbiota transplantation (FMT), engineered microorganisms, bacteriophages, diet, natural active substances, nanoparticles and compounds are examples of emerging non-antibiotic therapies that have received a great amount of attention. In this review, we collected data about different non-antibiotic therapies for CDI and provided a comprehensive analysis and detailed comparison of these therapies. The mechanism of action, therapeutic efficacy, and the strengths and weaknesses of these non-antibiotic therapies have been investigated to provide a basis for the reasonable alternative of non-antibiotic therapies for CDI. In summary, probiotics and FMT are currently the best choice for non-antibiotic therapy for CDI.}, }
@article {pmid31411731, year = {2019}, author = {Lion, T}, title = {Adenovirus persistence, reactivation, and clinical management.}, journal = {FEBS letters}, volume = {593}, number = {24}, pages = {3571-3582}, doi = {10.1002/1873-3468.13576}, pmid = {31411731}, issn = {1873-3468}, mesh = {Adenovirus Infections, Human/*diagnosis/drug therapy/prevention &amp; control ; Adenoviruses, Human/pathogenicity/*physiology ; Adult ; Age Factors ; Antiviral Agents/therapeutic use ; Blood/*virology ; Child ; Feces/*virology ; Humans ; Population Surveillance ; Stem Cell Transplantation/*adverse effects ; Virus Activation ; }, abstract = {Adenoviral infections continue posing a major threat in severely immunocompromised patients including particularly allogeneic stem cell transplant recipients. Although exogenous infections occur in some instances, the majority of invasive events appear to arise from viral reactivation. In the pediatric setting, adenoviruses were demonstrated to persist in the gastrointestinal tract, and the intestinal epithelium serves as the main site of viral replication preceding invasive infection. Regular monitoring of serial stool samples for the presence and load of adenoviruses has therefore become a routine diagnostic tool for post-transplant patient surveillance, and can serve as a trigger for early initiation of treatment. In the adult setting, the source of infection or reactivation is less clear, and monitoring of peripheral blood specimens is the predominant approach for patient surveillance. Timely initiation of antiviral treatment is reportedly required for prevention or successful control of disseminated disease mediated by adenoviruses, and appropriate diagnostic monitoring is therefore of paramount importance. Currently available antiviral agents and immune therapeutic approaches have not been able to entirely overcome the life-threatening courses of invasive adenoviral infections in the immunocompromised clinical setting.}, }
@article {pmid31408913, year = {2020}, author = {Sood, A and Singh, A and Mahajan, R and Midha, V and Mehta, V and Gupta, YK and Narang, V and Kaur, K}, title = {Acceptability, tolerability, and safety of fecal microbiota transplantation in patients with active ulcerative colitis (AT&amp;S Study).}, journal = {Journal of gastroenterology and hepatology}, volume = {35}, number = {3}, pages = {418-424}, doi = {10.1111/jgh.14829}, pmid = {31408913}, issn = {1440-1746}, mesh = {Adult ; Colitis, Ulcerative/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Humans ; Male ; Retrospective Studies ; Safety ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) targets gut microbiome dysbiosis and is an emerging therapy for ulcerative colitis (UC). Although initial results with FMT in patients with active UC are encouraging, data regarding its acceptability, tolerability, and safety are scant.<br><br>METHODS: A retrospective analysis of patients with active UC (Mayo clinic score&#xa0;&#x2265;&#xa0;4), who received multisession FMT (at weeks 0, 2, 6, 10, 14, 18, and 22) via colonoscopy between June 2016 and June 2018, was performed. Patient acceptability, tolerability, and immediate and long-term safety of the therapy were assessed.<br><br>RESULTS: Of the 129 patients with active UC who were offered FMT, 101 patients consented, giving acceptability of 78.3%. Fecal slurry retention time improved with each session (3.27&#xa0;&#xb1;&#xa0;1.06&#xa0;h for the first session vs 5.12&#xa0;&#xb1;&#xa0;0.5&#xa0;h for the seventh session). Abdominal discomfort, flatulence, abdominal distension, borborygmi, and low-grade fever (30.8%, 15.9%, 9.8%, 7.9%, and 7.6%, respectively) were the most common post-procedural short-term adverse events. Long-term adverse events included new-onset urticaria (n&#xa0;=&#xa0;2, 4.3%), arthritis/arthralgia (n&#xa0;=&#xa0;3, 6.5%), depression (n&#xa0;=&#xa0;1, 2.2%), partial sensorineural hearing loss (n&#xa0;=&#xa0;1, 2.2%), and allergic bronchitis (n&#xa0;=&#xa0;1, 2.2%). Thirteen (12.9%) patients dropped out because of adverse events.<br><br>CONCLUSION: Fecal microbiota transplantation appears to be a safe and well-tolerated procedure, with good acceptability in patients with active UC.}, }
@article {pmid31402904, year = {2019}, author = {Gargiullo, L and Del Chierico, F and D'Argenio, P and Putignani, L}, title = {Gut Microbiota Modulation for Multidrug-Resistant Organism Decolonization: Present and Future Perspectives.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1704}, pmid = {31402904}, issn = {1664-302X}, abstract = {The emergence of antimicrobial resistance (AMR) is of great concern to global public health. Treatment of multi-drug resistant (MDR) infections is a major clinical challenge: the increase in antibiotic resistance leads to a greater risk of therapeutic failure, relapses, longer hospitalizations, and worse clinical outcomes. Currently, there are no validated treatments for many MDR or pandrug-resistant (PDR) infections, and preventing the spread of these pathogens through hospital infection control procedures and antimicrobial stewardship programs is often the only tool available to healthcare providers. Therefore, new solutions to control the colonization of MDR pathogens are urgently needed. In this narrative review, we discuss current knowledge of microbiota-mediated mechanisms of AMR and strategies for MDR colonization control. We focus particularly on fecal microbiota transplantation for MDR intestinal decolonization and report updated literature on its current clinical use.}, }
@article {pmid31400364, year = {2019}, author = {Paramsothy, S and Kaakoush, NO}, title = {Reply.}, journal = {Gastroenterology}, volume = {157}, number = {4}, pages = {1165-1166}, doi = {10.1053/j.gastro.2019.08.005}, pmid = {31400364}, issn = {1528-0012}, mesh = {Bacteria ; *Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid31399369, year = {2019}, author = {Thingholm, LB and Rühlemann, MC and Koch, M and Fuqua, B and Laucke, G and Boehm, R and Bang, C and Franzosa, EA and Hübenthal, M and Rahnavard, A and Frost, F and Lloyd-Price, J and Schirmer, M and Lusis, AJ and Vulpe, CD and Lerch, MM and Homuth, G and Kacprowski, T and Schmidt, CO and Nöthlings, U and Karlsen, TH and Lieb, W and Laudes, M and Franke, A and Huttenhower, C}, title = {Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {2}, pages = {252-264.e10}, pmid = {31399369}, issn = {1934-6069}, support = {R01 HL144651/HL/NHLBI NIH HHS/United States ; P01 HL028481/HL/NHLBI NIH HHS/United States ; T32 HL069766/HL/NHLBI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; R01 GM083198/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification ; Biodiversity ; Diabetes Mellitus, Type 2/*complications ; Diet ; Dietary Supplements ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Germany ; Humans ; Iron/metabolism ; Magnesium/metabolism ; Male ; Metabolic Diseases/complications ; Metagenomics ; Mice ; Mice, Inbred C57BL ; Multivariate Analysis ; Nutrition Assessment ; Obesity/*complications/*microbiology ; Serum/metabolism ; }, abstract = {Obesity and type 2 diabetes (T2D) are metabolic disorders that are linked to microbiome alterations. However, their co-occurrence poses challenges in disentangling microbial features unique to each condition. We analyzed gut microbiomes of lean non-diabetic (n = 633), obese non-diabetic (n = 494), and obese individuals with T2D (n = 153) from German population and metabolic disease cohorts. Microbial taxonomic and functional profiles were analyzed along with medical histories, serum metabolomics, biometrics, and dietary data. Obesity was associated with alterations in microbiome composition, individual taxa, and functions with notable changes in Akkermansia, Faecalibacterium, Oscillibacter, and Alistipes, as well as in serum metabolites that correlated with gut microbial patterns. However, microbiome associations were modest for T2D, with nominal increases in Escherichia/Shigella. Medications, including antihypertensives and antidiabetics, along with dietary supplements including iron, were significantly associated with microbiome variation. These results differentiate microbial components of these interrelated metabolic diseases and identify dietary and medication exposures to consider in future studies.}, }
@article {pmid31398337, year = {2019}, author = {Riquelme, E and Zhang, Y and Zhang, L and Montiel, M and Zoltan, M and Dong, W and Quesada, P and Sahin, I and Chandra, V and San Lucas, A and Scheet, P and Xu, H and Hanash, SM and Feng, L and Burks, JK and Do, KA and Peterson, CB and Nejman, D and Tzeng, CD and Kim, MP and Sears, CL and Ajami, N and Petrosino, J and Wood, LD and Maitra, A and Straussman, R and Katz, M and White, JR and Jenq, R and Wargo, J and McAllister, F}, title = {Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes.}, journal = {Cell}, volume = {178}, number = {4}, pages = {795-806.e12}, pmid = {31398337}, issn = {1097-4172}, support = {K08 CA218690/CA/NCI NIH HHS/United States ; K12 CA088084/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; R25 CA056452/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Bacteria/classification ; Carcinoma, Pancreatic Ductal/*microbiology/*mortality ; Cell Line, Tumor ; Cohort Studies ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Pancreatic Neoplasms/*microbiology/*mortality ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA ; Survival Rate ; }, abstract = {Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS). We found higher alpha-diversity in the tumor microbiome of LTS patients and identified an intra-tumoral microbiome signature (Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii) highly predictive of long-term survivorship in both discovery and validation cohorts. Through human-into-mice fecal microbiota transplantation (FMT) experiments from STS, LTS, or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Our study demonstrates that PDAC microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and natural history of the disease.}, }
@article {pmid31396536, year = {2019}, author = {Zhou, GF and Jiang, YH and Ma, DF and Wang, YC and Yang, JL and Chen, JY and Chi, CY and Han, XW and Li, ZY and Li, X}, title = {Xiao-Qing-Long Tang Prevents Cardiomyocyte Hypertrophy, Fibrosis, and the Development of Heart Failure with Preserved Ejection Faction in Rats by Modulating the Composition of the Gut Microbiota.}, journal = {BioMed research international}, volume = {2019}, number = {}, pages = {9637479}, pmid = {31396536}, issn = {2314-6141}, mesh = {Administration, Oral ; Animals ; *Cardiomegaly/drug therapy/metabolism/microbiology/physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal/*pharmacology ; Fibrosis ; Gastrointestinal Microbiome/*drug effects ; *Heart Failure/drug therapy/metabolism/microbiology/physiopathology ; Male ; Myocytes, Cardiac/*metabolism ; Rats ; Rats, Inbred Dahl ; Stroke Volume/*drug effects ; }, abstract = {BACKGROUND: Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect.<br><br>METHODS: The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota.<br><br>RESULTS: Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF.<br><br>CONCLUSIONS: These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.}, }
@article {pmid31394793, year = {2019}, author = {El-Salhy, M and Hatlebakk, JG and Hausken, T}, title = {Diet in Irritable Bowel Syndrome (IBS): Interaction with Gut Microbiota and Gut Hormones.}, journal = {Nutrients}, volume = {11}, number = {8}, pages = {}, pmid = {31394793}, issn = {2072-6643}, mesh = {Cell Differentiation ; *Diet ; Diet, Carbohydrate-Restricted ; Enteroendocrine Cells/pathology ; Fecal Microbiota Transplantation ; Fermentation ; Gastrointestinal Hormones/*physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Irritable Bowel Syndrome/*diet therapy/*etiology/pathology ; Monosaccharides/administration &amp; dosage ; Polysaccharides/administration &amp; dosage ; Prebiotics/administration &amp; dosage ; Quality of Life ; Stem Cells/cytology ; }, abstract = {Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.}, }
@article {pmid31391921, year = {2019}, author = {Muscogiuri, G and Cantone, E and Cassarano, S and Tuccinardi, D and Barrea, L and Savastano, S and Colao, A and , }, title = {Gut microbiota: a new path to treat obesity.}, journal = {International journal of obesity supplements}, volume = {9}, number = {1}, pages = {10-19}, pmid = {31391921}, issn = {2046-2166}, abstract = {Obesity is a multifactorial disease resulting in excessive accumulation of adipose tissue. Over the last decade, growing evidence has identified the gut microbiota as a potential factor in the pathophysiology of both obesity and the related metabolic disorders. The gut microbiota is known to protect gastrointestinal mucosa permeability and to regulate the fermentation and absorption of dietary polysaccharides, perhaps explaining its importance in the regulation of fat accumulation and the resultant obesity. The proposed mechanisms by which the gut microbiota could contribute to the pathogenesis of obesity and the related metabolic diseases include: (a) a high abundance of bacteria that ferment carbohydrates, leading to increased rates of short-chain fatty acid (SCFA) biosynthesis, providing an extra source of energy for the host, that is eventually stored as lipids or glucose; (b) increased intestinal permeability to bacterial lipopolysaccharides (LPS), resulting in elevated systemic LPS levels that aggravate low-grade inflammation and insulin resistance; (c) increased activity of the gut endocannabinoid system. Fecal transplantation studies in germ-free mice have provided crucial insights into the potential causative role of the gut microbiota in the development of obesity and obesity-related disorders. Diet +/- bariatric surgery have been reported to modulate the gut microbiota, leading to lean host phenotype body composition. This review aims to report clinical evidence for a link of the gut microbiota with human obesity and obesity-related diseases, to provide molecular insights into these associations, and to address the effect of diet and bariatric surgery on the gut microbiota, including colonic microbiota, as a potential mechanism for promoting weight loss.}, }
@article {pmid31391545, year = {2020}, author = {Zhu, F and Guo, R and Wang, W and Ju, Y and Wang, Q and Ma, Q and Sun, Q and Fan, Y and Xie, Y and Yang, Z and Jie, Z and Zhao, B and Xiao, L and Yang, L and Zhang, T and Liu, B and Guo, L and He, X and Chen, Y and Chen, C and Gao, C and Xu, X and Yang, H and Wang, J and Dang, Y and Madsen, L and Brix, S and Kristiansen, K and Jia, H and Ma, X}, title = {Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice.}, journal = {Molecular psychiatry}, volume = {25}, number = {11}, pages = {2905-2918}, pmid = {31391545}, issn = {1476-5578}, mesh = {Animals ; Case-Control Studies ; Dopamine/metabolism ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Kynurenic Acid/metabolism ; Kynurenine/*metabolism ; Male ; Mice ; Schizophrenia/*metabolism/*microbiology ; *Schizophrenic Psychology ; Serotonin/metabolism ; Tryptophan/metabolism ; }, abstract = {Accumulating evidence suggests that gut microbiota plays a role in the pathogenesis of schizophrenia via the microbiota-gut-brain axis. This study sought to investigate whether transplantation of fecal microbiota from drug-free patients with schizophrenia into specific pathogen-free mice could cause schizophrenia-like behavioral abnormalities. The results revealed that transplantation of fecal microbiota from schizophrenic patients into antibiotic-treated mice caused behavioral abnormalities such as psychomotor hyperactivity, impaired learning and memory in the recipient animals. These mice also showed elevation of the kynurenine-kynurenic acid pathway of tryptophan degradation in both periphery and brain, as well as increased basal extracellular dopamine in prefrontal cortex and 5-hydroxytryptamine in hippocampus, compared with their counterparts receiving feces from healthy controls. Furthermore, colonic luminal filtrates from the mice transplanted with patients' fecal microbiota increased both kynurenic acid synthesis and kynurenine aminotransferase II activity in cultured hepatocytes and forebrain cortical slices. Sixty species of donor-derived bacteria showed significant difference between the mice colonized with the patients' and the controls' fecal microbiota, highlighting 78 differentially enriched functional modules including tryptophan biosynthesis function. In conclusion, our study suggests that the abnormalities in the composition of gut microbiota contribute to the pathogenesis of schizophrenia partially through the manipulation of tryptophan-kynurenine metabolism.}, }
@article {pmid31389816, year = {2019}, author = {Berbers, RM and Franken, IA and Leavis, HL}, title = {Immunoglobulin A and microbiota in primary immunodeficiency diseases.}, journal = {Current opinion in allergy and clinical immunology}, volume = {19}, number = {6}, pages = {563-570}, doi = {10.1097/ACI.0000000000000581}, pmid = {31389816}, issn = {1473-6322}, mesh = {Gastrointestinal Microbiome ; Homeostasis ; Humans ; Immunoglobulin A/*metabolism ; Immunoglobulin G/metabolism ; Immunoglobulin M/metabolism ; Inflammation ; Primary Immunodeficiency Diseases/*immunology ; }, abstract = {PURPOSE OF REVIEW: With the emergence of the microbiota as a potential driver of host inflammation, the role of iIgA is becoming increasingly important. This review discusses the current evidence regarding the effects of clinical IgA deficiency on the microbiota, and the possible role of microbial dysbiosis in driving inflammation in PID patients.<br><br>RECENT FINDINGS: The gut microbiota has been investigated in selective IgA deficiency and common variable immunodeficiency, revealing an important role for IgA in maintaining gut microbiota homeostasis, with disparate effects of IgA on symbionts and pathobionts. Although IgA deficiency is associated with microbial translocation and systemic inflammation, this may be partially compensated by adequate IgG and IgM induction in IgA deficiency but not in common variable immunodeficiency. Therapeutic strategies aimed at correction of the microbiota mostly focus on fecal microbiota transplantation. Whether this may reduce systemic inflammation in PID is currently unknown.<br><br>SUMMARY: Clinical IgA deficiency is associated with microbial dysbiosis and systemic inflammation. The evidence for microbiota-targeted therapies in PID is scarce, but indicates that IgA-based therapies may be beneficial, and that fecal microbiota transplantation is well tolerated in patients with antibody deficiency.}, }
@article {pmid31384699, year = {2019}, author = {Santiago, M and Eysenbach, L and Allegretti, J and Aroniadis, O and Brandt, LJ and Fischer, M and Grinspan, A and Kelly, C and Morrow, C and Rodriguez, M and Osman, M and Kassam, Z and Smith, MB and Timberlake, S}, title = {Microbiome predictors of dysbiosis and VRE decolonization in patients with recurrent C. difficile infections in a multi-center retrospective study.}, journal = {AIMS microbiology}, volume = {5}, number = {1}, pages = {1-18}, pmid = {31384699}, issn = {2471-1888}, abstract = {The gastrointestinal microbiome is intrinsically linked to the spread of antibiotic resistance. Antibiotic treatment puts patients at risk for colonization by opportunistic pathogens like vancomycin resistant Enterococcus and Clostridioides difficile by destroying the colonization resistance provided by the commensal microbiota. Once colonized, the host is at a much higher risk for infection by that pathogen. Furthermore, we know that microbiome community differences are associated with disease states, but we do not have a good understanding of how we can use these changes to classify different patient populations. To that end, we have performed a multicenter retrospective analysis on patients who received fecal microbiota transplants to treat recurrent Clostridioides difficile infection. We performed 16S rRNA gene sequencing on fecal samples collected as part of this study and used these data to develop a microbiome disruption index. Our microbiome disruption index is a simple index that is predictive across cohorts, indications, and batch effects. We are able to classify pre-fecal transplant vs post-fecal transplant samples in patients with recurrent C. difficile infection, and we are able to predict, using previously-published data from a cohort of patients receiving hematopoietic stem cell transplants, which patients would go on to develop bloodstream infections. Finally, we also identified patients in this cohort that were initially colonized with vancomycin resistant Enterococcus and that 92% (11/12) were decolonized after the transplant, but the microbiome disruption index was unable to predict such decolonization. We, however, were able to compare the relative abundance of different taxa between the two groups, and we found that increased abundance of Enterobacteriaceae predicts whether patients were colonized with vancomycin resistant Enterococcus. This work is an early step towards a better understanding of how microbiome predictors can be used to help improve patient care and patient outcomes.}, }
@article {pmid31384000, year = {2019}, author = {Džunková, M and Low, SJ and Daly, JN and Deng, L and Rinke, C and Hugenholtz, P}, title = {Defining the human gut host-phage network through single-cell viral tagging.}, journal = {Nature microbiology}, volume = {4}, number = {12}, pages = {2192-2203}, pmid = {31384000}, issn = {2058-5276}, mesh = {Bacteria/genetics/virology ; Bacteriophages/genetics/isolation &amp; purification/*physiology ; Feces/microbiology ; Gastrointestinal Microbiome/genetics/*physiology ; Gene Transfer, Horizontal ; Genome, Viral ; High-Throughput Nucleotide Sequencing ; Host Microbial Interactions/genetics/*physiology ; Humans ; Metagenome ; Microbial Interactions/genetics/*physiology ; Sequence Analysis, DNA ; Species Specificity ; Viruses/genetics ; }, abstract = {Viral discovery is accelerating at an unprecedented rate due to continuing advances in culture-independent sequence-based analyses. One important facet of this discovery is identification of the hosts of these recently characterized uncultured viruses. To this end, we have adapted the viral tagging approach, which bypasses the need for culture-based methods to identify host-phage pairings. Fluorescently labelled anonymous virions adsorb to unlabelled anonymous bacterial host cells, which are then individually sorted as host-phage pairs, followed by genome amplification and high-throughput sequencing to establish the identities of both the host and the attached virus(es). We demonstrate single-cell viral tagging using the faecal microbiome, including cross-tagging of viruses and bacteria between human subjects. A total of 363 unique host-phage pairings were predicted, most of which were subject-specific and involved previously uncharacterized viruses despite the majority of their bacterial hosts having known taxonomy. One-fifth of these pairs were confirmed by multiple individual tagged cells. Viruses targeting more than one bacterial species were conspicuously absent in the host-phage network, suggesting that phages are not major vectors of inter-species horizontal gene transfer in the human gut. A high level of cross-reactivity between phages and bacteria from different subjects was noted despite subject-specific viral profiles, which has implications for faecal microbiota transplant therapy.}, }
@article {pmid31383855, year = {2019}, author = {Sun, J and Xu, J and Ling, Y and Wang, F and Gong, T and Yang, C and Ye, S and Ye, K and Wei, D and Song, Z and Chen, D and Liu, J}, title = {Fecal microbiota transplantation alleviated Alzheimer's disease-like pathogenesis in APP/PS1 transgenic mice.}, journal = {Translational psychiatry}, volume = {9}, number = {1}, pages = {189}, pmid = {31383855}, issn = {2158-3188}, mesh = {Alzheimer Disease/genetics/*pathology/*therapy ; Amyloid beta-Protein Precursor/genetics ; Animals ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Mice ; Mice, Transgenic ; Neuronal Plasticity/physiology ; Phosphorylation ; Presenilin-1/genetics ; Spatial Learning/*physiology ; Treatment Outcome ; tau Proteins/metabolism ; }, abstract = {Alzheimer's disease (AD) is the most common dementia in the elderly. Treatment for AD is still a difficult task in clinic. AD is associated with abnormal gut microbiota. However, little is known about the role of fecal microbiota transplantation (FMT) in AD. Here, we evaluated the efficacy of FMT for the treatment of AD. We used an APPswe/PS1dE9 transgenic (Tg) mouse model. Cognitive deficits, brain deposits of amyloid-β (Aβ) and phosphorylation of tau, synaptic plasticity as well as neuroinflammation were assessed. Gut microbiota and its metabolites short-chain fatty acids (SCFAs) were analyzed by 16S rRNA sequencing and [1]H nuclear magnetic resonance (NMR). Our results showed that FMT treatment could improve cognitive deficits and reduce the brain deposition of amyloid-β (Aβ) in APPswe/PS1dE9 transgenic (Tg) mice. These improvements were accompanied by decreased phosphorylation of tau protein and the levels of Aβ40 and Aβ42. We observed an increases in synaptic plasticity in the Tg mice, showing that postsynaptic density protein 95 (PSD-95) and synapsin I expression were increased after FMT. We also observed the decrease of COX-2 and CD11b levels in Tg mice after FMT. We also found that FMT treatment reversed the changes of gut microbiota and SCFAs. Thus, FMT may be a potential therapeutic strategy for AD.}, }
@article {pmid31379808, year = {2019}, author = {Dhakal, S and Wang, L and Antony, L and Rank, J and Bernardo, P and Ghimire, S and Bondra, K and Siems, C and Lakshmanappa, YS and Renu, S and Hogshead, B and Krakowka, S and Kauffman, M and Scaria, J and LeJeune, JT and Yu, Z and Renukaradhya, GJ}, title = {Amish (Rural) vs. non-Amish (Urban) Infant Fecal Microbiotas Are Highly Diverse and Their Transplantation Lead to Differences in Mucosal Immune Maturation in a Humanized Germfree Piglet Model.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {1509}, pmid = {31379808}, issn = {1664-3224}, mesh = {Amish ; Animals ; Fecal Microbiota Transplantation/methods ; Feces/*microbiology ; Firmicutes/immunology ; Gastrointestinal Microbiome/*immunology ; Humans ; Infant ; Metagenome/immunology ; Microbiota/*immunology ; Mucous Membrane/*immunology/*microbiology ; Swine ; }, abstract = {The gut microbiome plays an important role in the immune system development, maintenance of normal health status, and in disease progression. In this study, we comparatively examined the fecal microbiomes of Amish (rural) and non-Amish (urban) infants and investigated how they could affect the mucosal immune maturation in germ-free piglets that were inoculated with the two types of infant fecal microbiota (IFM). Differences in microbiome diversity and structure were noted between the two types of fecal microbiotas. The fecal microbiota of the non-Amish (urban) infants had a greater relative abundance of Actinobacteria and Bacteroidetes phyla, while that of the Amish (rural) counterparts was dominated by Firmicutes. Amish infants had greater species richness compared with the non-Amish infants' microbiota. The fecal microbiotas of the Amish and the non-Amish infants were successfully transplanted into germ-free piglets, and the diversity and structure of the microbiota in the transplanted piglets remained similar at phylum level but not at the genus level. Principal coordinates analysis (PCoA) based on Weighted-UniFrac distance revealed distinct microbiota structure in the intestines of the transplanted piglets. Shotgun metagenomic analysis also revealed clear differences in functional diversity of fecal microbiome between Amish and non-Amish donors as well as microbiota transplanted piglets. Specific functional features were enriched in either of the microbiota transplanted piglet groups directly corresponding to the predominance of certain bacterial populations in their gut environment. Some of the colonized bacterial genera were correlated with the frequency of important lymphoid and myeloid immune cells in the ileal submucosa and mesenteric lymph nodes (MLN), both important for mucosal immune maturation. Overall, this study demonstrated that transplantation of diverse IFM into germ-free piglets largely recapitulates the differences in gut microbiota structure between rural (Amish) and urban (non-Amish) infants. Thus, fecal microbiota transplantation to germ-free piglets could be a useful large animal model system for elucidating the impact of gut microbiota on the mucosal immune system development. Future studies can focus on determining the additional advantages of the pig model over the rodent model.}, }
@article {pmid31379333, year = {2019}, author = {Allegretti, JR and Mullish, BH and Kelly, C and Fischer, M}, title = {The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications.}, journal = {Lancet (London, England)}, volume = {394}, number = {10196}, pages = {420-431}, doi = {10.1016/S0140-6736(19)31266-8}, pmid = {31379333}, issn = {1474-547X}, support = {MC_PC_17162/MRC_/Medical Research Council/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*trends ; Gastrointestinal Microbiome ; Humans ; Practice Guidelines as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {Developments in high-throughput microbial genomic sequencing and other systems biology techniques have given novel insight into the potential contribution of the gut microbiota to health and disease. As a result, an increasing number of diseases have been characterised by distinctive changes in the composition and functionality of the gut microbiota; however, whether such changes are cause, consequence, or incidental to the disease in question remains largely uncertain. Restoration of the gut microbiota to a premorbid state is a key novel therapeutic approach of interest, and faecal microbiota transplantation-the transfer of prescreened stool from healthy donors into the gastrointestinal tract of patients-is gaining increasing importance in both the clinical and research settings. At present, faecal microbiota transplantation is only recommended in the treatment of recurrent Clostridioides difficile infection, although a large number of trials are ongoing worldwide exploring other potential therapeutic indications.}, }
@article {pmid31375897, year = {2019}, author = {Prezioso, C and Ciotti, M and Obregon, F and Ambroselli, D and Rodio, DM and Cudillo, L and Gaziev, J and Mele, A and Nardi, A and Favalli, C and Arcese, W and Palamara, AT and Pietropaolo, V}, title = {Polyomaviruses shedding in stool of patients with hematological disorders: detection analysis and study of the non-coding control region's genetic variability.}, journal = {Medical microbiology and immunology}, volume = {208}, number = {6}, pages = {845-854}, pmid = {31375897}, issn = {1432-1831}, mesh = {Adult ; Child ; Feces/*virology ; Female ; *Genetic Variation ; Hematologic Neoplasms/*complications ; Humans ; Male ; Phylogeny ; Polyomavirus/classification/genetics/*isolation &amp; purification ; Polyomavirus Infections/*epidemiology/*virology ; Prevalence ; Real-Time Polymerase Chain Reaction ; Viral Load ; *Virus Shedding ; }, abstract = {Fragmented data are available on the human polyomaviruses (HPyVs) prevalence in the gastrointestinal tract. Rearrangements in the non-coding control region (NCCR) of JCPyV and BKPyV have been extensively studied and correlated to clinical outcome; instead, little information is available for KIPyV, WUPyV and MCPyV NCCRs. To get insights into the role of HPyVs in the gastrointestinal tract, we investigated JCPyV, BKPyV, KIPyV, WUPyV and MCPyV distribution among hematological patients in concomitance with gastrointestinal symptoms. In addition, NCCRs and VP1 sequences were examined to characterize the strains circulating among the enrolled patients. DNA was extracted from 62 stool samples and qPCR was carried out to detect and quantify JCPyV, BKPyV, KIPyV, WUPyV and MCPyV genomes. Positive samples were subsequently amplified and sequenced for NCCR and VP1 regions. A phylogenetic tree was constructed aligning the obtained VP1 sequences to a set of reference sequences. qPCR revealed low viral loads for all HPyVs searched. Mono and co-infections were detected. A significant correlation was found between gastrointestinal complications and KIPyV infection. Archetype-like NCCRs were found for JCPyV and BKPyV, and a high degree of NCCRs stability was observed for KIPyV, WUPyV and MCPyV. Analysis of the VP1 sequences revealed a 99% identity with the VP1 reference sequences. The study adds important information on HPyVs prevalence and persistence in the gastrointestinal tract. Gastrointestinal signs were correlated with the presence of KIPyV, although definitive conclusions cannot be drawn. HPyVs NCCRs showed a high degree of sequence stability, suggesting that sequence rearrangements are rare in this anatomical site.}, }
@article {pmid31375137, year = {2019}, author = {Lavelle, A and Hoffmann, TW and Pham, HP and Langella, P and Guédon, E and Sokol, H}, title = {Baseline microbiota composition modulates antibiotic-mediated effects on the gut microbiota and host.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {111}, pmid = {31375137}, issn = {2049-2618}, mesh = {Amoxicillin-Potassium Clavulanate Combination/*administration &amp; dosage ; Animals ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacteria/classification/*drug effects ; Bacterial Physiological Phenomena ; Colon/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Gene Expression Profiling ; Germ-Free Life ; Humans ; Male ; Mice ; *Microbiota ; }, abstract = {BACKGROUND: Normal mammalian development and homeostasis are dependent upon the gut microbiota. Antibiotics, essential for the treatment and prophylaxis of bacterial infections, can have collateral effects on the gut microbiota composition, which can in turn have far-reaching and potentially deleterious consequences for the host. However, the magnitude and duration of such collateral effects appear to vary between individuals. Furthermore, the degree to which such perturbations affect the host response is currently unclear. We aimed to test the hypothesis that different human microbiomes have different responses to a commonly prescribed antibiotic and that these differences may impact the host response.<br><br>METHODS: Germ-free mice (n = 30) humanized with the microbiota of two unrelated donors (A and B) were subjected to a 7-day antibiotic challenge with amoxicillin-clavulanate ("co-amoxiclav"). Microbiome and colonic transcriptome analysis was performed, pre (day 0) and post antibiotics (day 8) and subsequently into recovery (days 11 and 18).<br><br>RESULTS: Unique community profiles were evident depending upon the donor, with donor A recipient mice being dominated by Prevotella and Faecalibacterium and donor B recipient mice dominated by Bacteroides and Parabacteroides. Donor A mice underwent a marked destabilization of their microbiota following antibiotic treatment, while donor B mice maintained a more stable profile. Dramatic and overlapping alterations in the host transcriptome were apparent following antibiotic challenge in both groups. Despite this overlap, donor A mice experienced a more significant alteration in gene expression and uniquely showed correlations between host pathways and key microbial genera.<br><br>CONCLUSIONS: Germ-free mice humanized by different donor microbiotas maintain distinct microbiome profiles, which respond in distinct ways to antibiotic challenge and evince host responses that parallel microbiome disequilibrium. These results suggest that inter-individual variation in the gut microbiota may contribute to personalized host responses following microbiota perturbation.}, }
@article {pmid31373710, year = {2019}, author = {Koopman, N and Molinaro, A and Nieuwdorp, M and Holleboom, AG}, title = {Review article: can bugs be drugs? The potential of probiotics and prebiotics as treatment for non-alcoholic fatty liver disease.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {50}, number = {6}, pages = {628-639}, doi = {10.1111/apt.15416}, pmid = {31373710}, issn = {1365-2036}, support = {016.146.327//ZONMW-VIDI/International ; //Dutch Heart Foundation/International ; //Gilead Research scholarship/International ; //Amsterdam UMC Fellowship/International ; //TKI-PPP/International ; }, mesh = {Animals ; Bariatric Surgery ; Fecal Microbiota Transplantation ; Humans ; Microbiota ; Non-alcoholic Fatty Liver Disease/*therapy ; *Prebiotics ; Probiotics/*therapeutic use ; Synbiotics ; }, abstract = {BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver condition. A major current research effort is ongoing to find potential strategies to treat NAFLD-non-alcoholic steatohepatitis (NASH), with special attention to the gut microbiota. Multiple animal studies and pilot clinical trials are assessing different gut microbiota modulating strategies such as faecal microbiota transplantation, antibiotics, probiotics, prebiotics and synbiotics.<br><br>AIM: To review the role of microbiota in NAFLD-NASH and determine whether pro- and prebiotics have potential as treatment METHODS: Information was obtained from critically reviewing literature on PubMed on targeting the gut microbiota in NAFLD. Search terms included NAFLD, NASH, non-alcoholic fatty liver disease, steatohepatitis; combined with microbiome, microbiota, gut bacteria, probiotics and prebiotics.<br><br>RESULTS: Animal studies and the first emerging studies in humans show promising results for both the common probiotics Lactobacillus, Bifidobacterium and Streptococci as for short chain fatty acid (SCFA) butyrate-producing bacteria. Also, prebiotics have positive effects on different mechanisms underlying NAFLD-NASH.<br><br>CONCLUSIONS: The most promising strategies thus far developed to alter the microbiome in NAFLD-NASH are probiotics and prebiotics. However, pre- and probiotic treatment of NAFLD-NASH is relatively new and still under development. Actual understanding of the involved mechanisms is lacking and changes in the intestinal microbiota composition after treatment are rarely measured. Furthermore, large clinical trials with comparative endpoints are unavailable. Personalised treatment based on metagenomics gut microbiota analysis will probably be part of the future diagnosis and treatment of NAFLD-NASH.}, }
@article {pmid31370803, year = {2019}, author = {Ma, Y and Xu, X and Li, M and Cai, J and Wei, Q and Niu, H}, title = {Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {25}, number = {1}, pages = {35}, pmid = {31370803}, issn = {1528-3658}, mesh = {Animals ; Enzyme-Linked Immunosorbent Assay ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; High-Throughput Nucleotide Sequencing ; Inflammation/*microbiology ; Lupus Erythematosus, Systemic/*immunology/*microbiology ; Mice ; Mice, Inbred C57BL ; Microbiota/*physiology ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease whose onset and progression are affected by genetic and environmental factors. The purpose of this study is to identify the influence of gut microbiota in the pathogenesis of SLE, and to investigate the mechanism involved.<br><br>METHODS: Fecal microbiota from C57/BL6 mice and SLE prone mice were examined using next-generation sequencing (NGS). Germ free mice were given fecal microbiota transplantation (FMT), and their gut microbiome and gene expression in recipients' colons were examined by NGS. The anti-double stranded DNA (anti-dsDNA) antibodies in recipients were determined using an enzyme-linked immunosorbent assay (ELISA). The immune cell profiles of mice were analyzed by flow cytometry at the 3rd week after FMT, and the expression of genes associated with SLE after FMT was determined using quantitative real-time PCR (qRT-PCR).<br><br>RESULTS: The fecal microbiota of SLE mice had lower community richness and diversity than healthy mice. Fecal microbiota of recipient mice were similar to their donors. Fecal microbiome from SLE mice could lead to a significant increase of anti-dsDNA antibodies and promote the immune response in recipient mice. Our results also indicated that fecal microbiome from SLE mice resulted in significant changes in the distribution of immune cells and upregulated expression of certain lupus susceptibility genes.<br><br>CONCLUSIONS: SLE is associated with alterations of gut microbiota. Fecal microbiome from SLE mice can induce the production of anti-dsDNA antibodies in germ free mice and stimulate the inflammatory response, and alter the expression of SLE susceptibility genes in these mice.}, }
@article {pmid31369420, year = {2019}, author = {Shin, JH and Warren, CA}, title = {Prevention and treatment of recurrent Clostridioides difficile infection.}, journal = {Current opinion in infectious diseases}, volume = {32}, number = {5}, pages = {482-489}, doi = {10.1097/QCO.0000000000000587}, pmid = {31369420}, issn = {1473-6527}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/*prevention &amp; control/*therapy ; Fecal Microbiota Transplantation/methods ; Humans ; Probiotics/therapeutic use ; Recurrence ; Secondary Prevention/methods ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Clostridioides difficile infection (CDI) is a significant burden on the health system, especially due to high recurrence rates. Since the beginning of the CDI epidemic in early 2000s, many strategies for combatting recurrence have been explored, with moderate success so far. This review will focus on the most recent developments in recurrent CDI prevention and treatment.<br><br>RECENT FINDINGS: There are two main mechanisms of CDI recurrence: alteration in microbiome and poor antibody response. Development of new antibiotics aims to minimize damage to the microbiome. Fecal transplant or other microbiome replacement therapies seek to replenish the missing elements in the microbiome. Fecal microbiota transplant is the most effective treatment for prevention of CDI recurrenceso far, but is difficult to standardize and regulate, leading to efforts to develop microbiome-derived therapeutics. A deficiency in developing antibodies to C. difficile toxins is another mechanism of recurrence. Active immunization using toxoid vaccines or passive immunization using mAbs address this aspect.<br><br>SUMMARY: There are promising new treatments for recurrent CDI in development. Fecal microbiota transplant remains the most effective therapy for multiply recurrent CDI. New antibiotics, microbiome-derived therapeutics, and immunologic therapies are in development.}, }
@article {pmid31368781, year = {2019}, author = {Carding, S}, title = {The importance of studying the human intestinal microbiome in its entirety: an interview with Simon Carding.}, journal = {Future microbiology}, volume = {14}, number = {}, pages = {837-838}, doi = {10.2217/fmb-2019-0156}, pmid = {31368781}, issn = {1746-0921}, support = {BBS/E/F/000PR10355/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Autoimmune Diseases/microbiology/therapy/virology ; Biomedical Research/trends ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; History, 21st Century ; *Host Microbial Interactions ; Humans ; Inflammatory Bowel Diseases/microbiology/therapy/virology ; Intestines/microbiology/virology ; }, }
@article {pmid31368397, year = {2020}, author = {Parker, A and Fonseca, S and Carding, SR}, title = {Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health.}, journal = {Gut microbes}, volume = {11}, number = {2}, pages = {135-157}, pmid = {31368397}, issn = {1949-0984}, support = {BBS/E/F000PR10355/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J004529/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10355/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Bacteria/*metabolism ; Biological Transport ; *Blood-Brain Barrier/metabolism/microbiology ; Brain/*metabolism ; Cytokines/metabolism ; Dendritic Cells/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism/microbiology ; Homeostasis ; Humans ; Intestinal Mucosa/metabolism ; Neurodegenerative Diseases/microbiology ; Prebiotics ; Probiotics ; Signal Transduction ; }, abstract = {The human gastrointestinal (gut) microbiota comprises diverse and dynamic populations of bacteria, archaea, viruses, fungi, and protozoa, coexisting in a mutualistic relationship with the host. When intestinal homeostasis is perturbed, the function of the gastrointestinal tract and other organ systems, including the brain, can be compromised. The gut microbiota is proposed to contribute to blood-brain barrier disruption and the pathogenesis of neurodegenerative diseases. While progress is being made, a better understanding of interactions between gut microbes and host cells, and the impact these have on signaling from gut to brain is now required. In this review, we summarise current evidence of the impact gut microbes and their metabolites have on blood-brain barrier integrity and brain function, and the communication networks between the gastrointestinal tract and brain, which they may modulate. We also discuss the potential of microbiota modulation strategies as therapeutic tools for promoting and restoring brain health.}, }
@article {pmid31367877, year = {2020}, author = {Yang, Z and Bu, C and Yuan, W and Shen, Z and Quan, Y and Wu, S and Zhu, C and Wang, X}, title = {Fecal Microbiota Transplant via Endoscopic Delivering Through Small Intestine and Colon: No Difference for Crohn's Disease.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {1}, pages = {150-157}, pmid = {31367877}, issn = {1573-2568}, support = {81272736//National Natural Science Foundation of China/International ; }, mesh = {Adult ; China ; Colon/*microbiology ; *Colonoscopy/adverse effects ; Crohn Disease/diagnosis/microbiology/*therapy ; Double-Blind Method ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Female ; *Gastrointestinal Microbiome ; *Gastroscopy/adverse effects ; Humans ; Intestine, Small/*microbiology ; Male ; Middle Aged ; Prospective Studies ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disorder associated with intestinal dysbiosis. This study aimed to determine the efficacy and safety of different methods of fecal microbiota transplantation (FMT), a potential therapy for CD.<br><br>METHODS: Patients with CD were randomized to receive FMT by gastroscopy or colonoscopy; a second transplantation was performed 1&#xa0;week later. Patients were assessed by clinical evaluation and serum testing (at weeks 1, 2, 4, 6, and 8) and endoscopy (8&#xa0;weeks after transplantation). Fecal DNA was extracted and analyzed using the Illuminal sequencing platform.<br><br>RESULTS: Of the 27 patients included in the study, clinical remission was achieved in 18 (66.7%); no significant difference was seen between the two methods. 76.9% of gastroscopy group patients and 64.3% of colonoscopy group patients experienced mild adverse events during or shortly after treatment. Microbiota diversity analyses showed that, in comparison with the donors, patients had lower operational taxonomic units (OTU; 117 vs. 258, p&#x2009;<&#x2009;0.05) and Shannon diversity index (2.05 vs. 3.46, p&#x2009;<&#x2009;0.05). The CD patients showed a significant increase in OTU and Shannon diversity index 2&#xa0;weeks after FMT. In comparison with the donors, CD patients had lower levels of Bacteroides, Eubacterium, faecalibacterium, and Roseburia, and higher levels of Clostridium, Cronobacter, Fusobacterium, and Streptococcus.<br><br>CONCLUSIONS: FMT was seen to be safe and effective in this cohort of patients with CD. No significant differences in clinical remission rate and adverse events were seen between the gastroscopy and colonoscopy groups. FMT was seen to increase the species richness in CD patients.}, }
@article {pmid31367159, year = {2019}, author = {Liu, MT and Huang, YJ and Zhang, TY and Tan, LB and Lu, XF and Qin, J}, title = {Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosis via gut microbiota.}, journal = {World journal of gastroenterology}, volume = {25}, number = {27}, pages = {3590-3606}, pmid = {31367159}, issn = {2219-2840}, mesh = {Animals ; *Caloric Restriction ; Combined Modality Therapy/methods ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Intestinal Mucosa/drug effects/metabolism/microbiology ; Lipid Metabolism/drug effects ; Lipids/blood ; Liver/drug effects/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/etiology/microbiology/*therapy ; Obesity/etiology/microbiology/*therapy ; Plant Extracts/*administration &amp; dosage ; Treatment Outcome ; }, abstract = {BACKGROUND: Obesity is a major risk factor for a variety of diseases such as diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Restricting energy intake, or caloric restriction (CR), can reduce body weight and improve metabolic parameters in overweight or obese patients. We previously found that Lingguizhugan decoction (LZD) in combination with CR can effectively lower plasma lipid levels in patients with metabolic syndrome. However, the mechanism underlying CR and LZD treatment is still unclear.<br><br>AIM: To investigate whether CR and LZD improve metabolic parameters by modulating gut microbiota.<br><br>METHODS: We extracted the water-soluble components out of raw materials and dried as LZD extracts. Eight-week old male C57BL/6 mice were treated with a 3-d treatment regime that included 24 h-fasting followed by gavage of LZD extracts for 2 consecutive days, followed by a normal diet (ND) ad libitum for 16 wk. To test the effects of gut microbiota on diet-induced obesity, 8-wk old male C57BL/6 mice received fecal microbiota transplantation (FMT) from CR and LZD-treated mice every 3 d and were fed with high-fat diet (HFD) ad libitum for 16 wk. Control mice received either saline gavage or FMT from ND-fed mice receiving saline gavage as mentioned above. Body weight was monitored bi-weekly. Food consumption of each cage hosting five mice was recorded weekly. To monitor blood glucose, total cholesterol, and total triglycerides, blood samples were collected via submandibular bleeding after 6 h fasting. Oxygen consumption rate was monitored with metabolic cages. Feces were collected, and fecal DNA was extracted. Profiles of gut microbiota were mapped by metagenomic sequencing.<br><br>RESULTS: We found that CR and LZD treatment significantly reduced the body weight of mice fed with ND (28.71 &#xb1; 0.29 vs 28.05 &#xb1; 0.15, P < 0.05), but did not affect plasma total cholesterol or total triglyceride levels. We then transplanted the fecal microbiota collected from CR and LZD-treated mice under ND feeding to HFD-fed mice. Intriguingly, transplanting the mice with fecal microbiota from CR and LZD-treated mice potently reduced body weight (44.95 &#xb1; 1.02 vs 40.53 &#xb1; 0.97, P < 0.001). FMT also reduced HFD-induced hepatosteatosis, in addition to improved glycemic control. Mechanistic studies found that FMT increased OCR of the mice and suppressed the expression and protein abundance of lipogenic genes in the liver. Metagenomic analysis revealed that HFD drastically altered the profile of gut microbiota, and FMT modified the profile of the gut microbiota.<br><br>CONCLUSION: Our study suggests that CR and LZD improve metabolic parameters by modulating gut microbiota.}, }
@article {pmid31366464, year = {2019}, author = {Galloway-Peña, JR and Jenq, RR}, title = {The only thing that stops a bad microbiome, is a good microbiome.}, journal = {Haematologica}, volume = {104}, number = {8}, pages = {1511-1513}, pmid = {31366464}, issn = {1592-8721}, support = {K01 AI143881/AI/NIAID NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; }, mesh = {Drug Resistance, Microbial ; Drug Resistance, Multiple ; *Fecal Microbiota Transplantation ; Humans ; Microbiota/*physiology ; Transplantation, Homologous ; }, }
@article {pmid31363779, year = {2019}, author = {Woodworth, MH and Hayden, MK and Young, VB and Kwon, JH}, title = {The Role of Fecal Microbiota Transplantation in Reducing Intestinal Colonization With Antibiotic-Resistant Organisms: The Current Landscape and Future Directions.}, journal = {Open forum infectious diseases}, volume = {6}, number = {7}, pages = {}, pmid = {31363779}, issn = {2328-8957}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; K23 AI137321/AI/NIAID NIH HHS/United States ; U54 CK000607/CK/NCEZID CDC HHS/United States ; U54CK000481/ACL/ACL HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; U54 CK000481/CK/NCEZID CDC HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; }, abstract = {The intestinal tract is a recognized reservoir of antibiotic-resistant organisms (ARO), and a potential target for strategies to reduce ARO colonization. Microbiome therapies such as fecal microbiota transplantation (FMT) have been established as an effective treatment for recurrent Clostridioides difficile infection and may be an effective approach for reducing intestinal ARO colonization. In this article, we review the current published literature on the role of FMT for eradication of intestinal ARO colonization, review the potential benefit and limitations of the use of FMT in this setting, and outline a research agenda for the future study of FMT for intestinal ARO colonization.}, }
@article {pmid31362781, year = {2019}, author = {Wang, X and Tsai, T and Deng, F and Wei, X and Chai, J and Knapp, J and Apple, J and Maxwell, CV and Lee, JA and Li, Y and Zhao, J}, title = {Longitudinal investigation of the swine gut microbiome from birth to market reveals stage and growth performance associated bacteria.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {109}, pmid = {31362781}, issn = {2049-2618}, mesh = {Animal Feed ; Animals ; Bacteria/*classification ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Genetic Variation ; Lactation ; Longitudinal Studies ; RNA, Ribosomal, 16S/genetics ; Swine/*growth &amp; development/*microbiology ; }, abstract = {BACKGROUND: Despite recent advances in the understanding of the swine gut microbiome at different growth stages, a comprehensive longitudinal study of the lifetime (birth to market) dynamics of the swine gut microbiome is lacking.<br><br>RESULTS: To fill in this gap of knowledge, we repeatedly collected a total of 273 rectal swabs from 18 pigs during lactation (day (d) 0, 11, 20), nursery (d 27, 33, 41, 50, 61), growing (d 76, 90, 104, 116), and finishing (d 130, 146, 159, 174) stages. DNA was extracted and subjected to sequencing with an Illumina Miseq sequencer targeting the V4 region of the 16S rRNA gene. Sequences were analyzed with the Deblur algorithm in the QIIME2 package. A total of 19 phyla were detected in the lifetime pig gut microbiome with Firmicutes and Bacteroidetes being the most abundant. Alpha diversity including community richness (e.g., number of observed features) and diversity (e.g., Shannon index) showed an overall increasing trend. Distinct shifts in microbiome structure along different growth stages were observed. LEfSe analysis revealed 91 bacterial features that are stage-specific. To validate these discoveries, we performed fecal microbiota transplantation (FMT) by inoculating weanling pigs with mature fecal microbiota from a growing stage pig. Similar stage-specific patterns in microbiome diversity and structures were also observed in both the FMT pigs and their littermates. Although FMT remarkably increased growth performance, it did not change the overall swine gut microbiome. Only a few taxa including those associated with Streptococcus and Clostridiaceae were enriched in the FMT pigs. These data, together with several other lines of evidence, indicate potential roles these taxa play in promoting animal growth performance. Diet, especially crude fiber from corn, was a major factor shaping the swine gut microbiome. The priority effect, i.e., the order and timing of species arrival, was more evident in the solid feed stages.<br><br>CONCLUSIONS: The distinct stage-associated swine gut microbiome may be determined by the differences in diet and/or gut physiology at different growth stages. Our study provides insight into mechanisms governing gut microbiome succession and also underscores the importance of optimizing stage-specific probiotics aimed at improving animal health and production.}, }
@article {pmid31361890, year = {2019}, author = {Haber, SL and Raney, CRK and Larson, TL and Lau, JP}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {76}, number = {13}, pages = {935-942}, doi = {10.1093/ajhp/zxz078}, pmid = {31361890}, issn = {1535-2900}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Patient Education as Topic/organization &amp; administration ; Pharmacists/*organization &amp; administration ; Professional Role ; Randomized Controlled Trials as Topic ; Recurrence ; Tissue and Organ Harvesting/methods ; Tissue and Organ Procurement/organization &amp; administration ; Treatment Outcome ; }, abstract = {PURPOSE: Randomized controlled trials investigating the efficacy and safety of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) are reviewed, and practical issues for pharmacists to consider are discussed.<br><br>SUMMARY: Eight randomized controlled trials evaluating the use of FMT for recurrent CDI were analyzed. The trials varied in the type of sample (fresh, frozen, lyophilized), route of administration (nasogastric tube, colonoscopy, enema, oral), and comparator agent (different type of FMT, vancomycin). Efficacy rates ranged from 43.8% to 96.2% with FMT, and safety data were relatively similar. With these favorable data, pharmacists are likely to be involved at multiple steps in the delivery of FMT to patients with recurrent CDI, including the procurement, documentation, and administration of various products and patient education.<br><br>CONCLUSION: FMT is an option for recurrent CDI that is supported by findings of randomized controlled trials, although a preferred method for the delivery remains to be defined. Pharmacists can play an important role in the successful management of patients with recurrent CDI who may benefit from FMT.}, }
@article {pmid31361420, year = {2019}, author = {Ooijevaar, RE and van Rossen, TM and Vandenbroucke-Grauls, CMJE and Budding, AE and Kneepkens, CMF and de Meij, TGJ}, title = {[Faecal transplants for children with recurrent infections].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {163}, number = {}, pages = {}, pmid = {31361420}, issn = {1876-8784}, mesh = {Adolescent ; Anti-Bacterial Agents/adverse effects ; Child, Preschool ; Clostridioides difficile ; Clostridium Infections/chemically induced/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Otitis Media/drug therapy ; Recurrence ; }, abstract = {BACKGROUND: Clostridioides difficile infection is a relatively rare cause of diarrhoea in children, but there are frequent recurrences when it occurs, despite targeted antibiotic treatment.<br><br>CASE DESCRIPTIONS: A 2-year-old boy with concomitant motility disorder and a 14-year-old girl with Down syndrome experienced several infections with C. difficile, respectively after the use of antibiotics for otitis media and extended use of antibiotics in addition to chemotherapy. Both were treated successfully with faecal transplants.<br><br>CONCLUSION: Clostridioides difficile infections occur in children, mainly after extended use of antibiotics or when the immune system is impaired. In case of recurring C. difficile infections, children can be treated safely and effectively with faecal transplants.}, }
@article {pmid32421966, year = {2019}, author = {Akash, MSH and Fiayyaz, F and Rehman, K and Sabir, S and Rasool, MH}, title = {Gut Microbiota and Metabolic Disorders: Advances in Therapeutic Interventions.}, journal = {Critical reviews in immunology}, volume = {39}, number = {4}, pages = {223-237}, doi = {10.1615/CritRevImmunol.2019030614}, pmid = {32421966}, issn = {1040-8401}, mesh = {Animals ; Bacteroides/*physiology ; Diabetes Mellitus, Type 2/*metabolism ; Dysbiosis ; Fatty Acids/*metabolism ; Firmicutes/*physiology ; Gastrointestinal Microbiome/*immunology ; Host-Pathogen Interactions ; Humans ; Inflammation/*metabolism ; Metabolic Diseases ; Obesity/*metabolism ; }, abstract = {Human gut microbiota consist of numerous microorganisms, but the most abundant species are Bacteroides and Firmicutes. Each human possesses a specific gut microbiota, which can be altered by diet, antibiotics, lifestyle, and genetic background. Gut microbiota perform vital functions, but in this article, we aimed to elaborate the effects of modified composition of microbiota on host metabolism. Ligands for G protein coupled receptors (GPCRs) are short-chain fatty acids (SCFAs) located on endocrine glands, epithelial cells, and adipocytes. SCFAs are produced in the distal gut by bacterial fermentation of nondigestible polysaccharides; they induce the various beneficial effects including decrease serum glucose level, insulin resistance, as well as inflammation; and they increase glucagon-like peptide-1 (GLP-1) secretion. Fasting-induced adipose factor (FIAF) is suppressed by gut microbiota and results in the increased storage of fatty acids in the adipose tissues and liver. An increased lipopolysaccharide level due to altered gut microflora cause the initiation of inflammation associated with type 2 diabetes mellitus (T2DM). Intestinal dysbiosis and metabolic endotoxemia are considered key mechanisms that seem to be associated with the development of T2DM and obesity. Therapeutic interventions that can be used for the treatment of diabetes include metformin, dietary modulation, probiotics, prebiotics, fecal microbiota transplantation and bariatric surgery.}, }
@article {pmid32313396, year = {2018}, author = {Mullen, KR and Yasuda, K and Divers, TJ and Weese, JS}, title = {Equine faecal microbiota transplant: Current knowledge, proposed guidelines and future directions.}, journal = {Equine veterinary education}, volume = {30}, number = {3}, pages = {151-160}, pmid = {32313396}, issn = {0957-7734}, abstract = {While certainly not a novel concept, faecal microbiota transplant (FMT) has recently garnered renewed interest in veterinary medicine due to its remarkable success in treating recurrent Clostridium difficile infection (CDI) in man. There is a dearth of information on indications and efficacy of FMT for the treatment of gastrointestinal disorders in the horse; however, based on evidence in man and other veterinary species, and anecdotal reports in horses, FMT may be a useful treatment for selected cases of acute and chronic diarrhoea and inflammatory bowel disease (IBD) in the horse. In the absence of evidence, expert opinion is offered on case selection and FMT procedure. More research is needed to explore the efficacy, indications and optimal preparation, storage and delivery of FMT to horses.}, }
@article {pmid31359254, year = {2019}, author = {Oksi, J and Aalto, A and Säilä, P and Partanen, T and Anttila, VJ and Mattila, E}, title = {Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {38}, number = {10}, pages = {1947-1952}, pmid = {31359254}, issn = {1435-4373}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*administration &amp; dosage/adverse effects ; Antibodies, Monoclonal/*administration &amp; dosage/adverse effects ; Broadly Neutralizing Antibodies/*administration &amp; dosage/adverse effects ; Clostridioides difficile/*drug effects ; Clostridium Infections/*prevention &amp; control ; Female ; Finland ; Hospitals, University ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Secondary Prevention/*methods ; Treatment Outcome ; Young Adult ; }, abstract = {Reports on real-world experience on efficacy of bezlotoxumab (BEZ) has been lacking thus far. We retrospectively studied the efficacy and safety of BEZ in preventing the recurrence of Clostridium difficile infection (CDI) in five university hospitals in Finland. Seventy-three percent of our 46 patients remained free of recurrence in the following 3 months and the performance remained as 71% effective also among immunocompromised patients. In severe CDI, BEZ prevented recurrence in 63% of cases. From our study patients, 78% had three or more known risk factors for recurrence of CDI. Eight of our patients were waiting for fecal microbiota transplantation but after stopping the antibiotics that were continued to prevent recurrence of CDI and after receiving BEZ, all remained free of recurrence and did not need the procedure. Success with BEZ as an adjunctive treatment in preventing recurrence of CDI in high-risk patients may be rated as high. Among a subgroup of our patients, those already evaluated to be in need of fecal microbiota transplantation, BEZ seems to be an alternative option.}, }
@article {pmid31359164, year = {2019}, author = {Urits, I and Capuco, A and Sharma, M and Kaye, AD and Viswanath, O and Cornett, EM and Orhurhu, V}, title = {Stem Cell Therapies for Treatment of Discogenic Low Back Pain: a Comprehensive Review.}, journal = {Current pain and headache reports}, volume = {23}, number = {9}, pages = {65}, pmid = {31359164}, issn = {1534-3081}, mesh = {Animals ; Embryonic Stem Cells/transplantation ; Humans ; Intervertebral Disc Degeneration/complications/diagnosis/*therapy ; Low Back Pain/diagnosis/etiology/*therapy ; Mesenchymal Stem Cell Transplantation/*methods/trends ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Discogenic low back pain (DLBP) stems from pathology in one or more intervertebral discs identified as the root cause of the pain. It is the most common type of chronic low back pain (LBP), representing 26-42% of attributable cases.<br><br>RECENT FINDINGS: The clinical presentation of DLBP includes increased pain when sitting, coughing, or sneezing, and experiencing relief when standing or ambulating. Dermatomal radiation of pain to the lower extremity and neurological symptoms including numbness, motor weakness, and urinary or fecal incontinence are signs of advanced disease with disc prolapse, nerve root compression, or spinal stenosis. Degenerative disc disease is caused by both a decrease in disc nutrient supply causing decreased oxygen, lowered pH, and lessened ability of the intervertebral disc (IVD) to respond to increased load or injury; moreover, changes in the extracellular matrix composition cause weakening of the tissue and skewing the extracellular matrix's (ECM) harmonious balance between catabolic and anabolic factors for cell turnover in favor of catabolism. Thus, the degeneration of the disc causes a shift from type II to type I collagen expression by NP cells and a decrease in aggrecan synthesis leads to dehydrated matrix cells ultimately with loss of swelling pressure needed for mechanical support. Cell-based therapies such as autologous nucleus pulposus cell re-implantation have in animal models and human trials shown improvements in LBP score, retention of hydration in IVD, and increased disc height. Percutaneously delivered multipotent mesenchymal stem cell (MSC) therapy has been proposed as a potential means to uniquely ameliorate discogenic LBP holistically through three mechanisms: mitigation of primary nociceptive disc pain, slow or reversal of the catabolic metabolism, and restoration of disc tissue. Embryonic stem cells (ESCs) can differentiate into cells of all three germ layers in vitro, but their use is hindered related to ethical concerns, potential for immune rejection after transplantation, disease, and teratoma formation. Another similar approach to treating back pain is transplantation of the nucleus pulposus, which, like stem cell therapy, seeks to address the underlying cause of intervertebral disc degeneration by aiming to reverse the destructive inflammatory process and regenerate the proteoglycans and collagen found in healthy disc tissue. Preliminary animal models and clinical studies have shown mesenchymal stem cell implantation as a potential therapy for IVD regeneration and ECM restoration via a shift towards favorable anabolic balance and reduction of pain.}, }
@article {pmid31356805, year = {2019}, author = {Kellermayer, R}, title = {Roseburia Species: Prime Candidates for Microbial Therapeutics in Inflammatory Bowel Disease.}, journal = {Gastroenterology}, volume = {157}, number = {4}, pages = {1164-1165}, doi = {10.1053/j.gastro.2019.05.073}, pmid = {31356805}, issn = {1528-0012}, mesh = {Clostridiales ; *Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases ; }, }
@article {pmid31354831, year = {2019}, author = {Nowak, A and Hedenstierna, M and Ursing, J and Lidman, C and Nowak, P}, title = {Efficacy of Routine Fecal Microbiota Transplantation for Treatment of Recurrent Clostridium difficile Infection: A Retrospective Cohort Study.}, journal = {International journal of microbiology}, volume = {2019}, number = {}, pages = {7395127}, pmid = {31354831}, issn = {1687-918X}, abstract = {BACKGROUND: Patients with recurrent Clostridium difficile infections (CDIs) constitute an increasing treatment problem. Fecal microbiota transplantation (FMT) has shown promising results of treating recurrent CDI, where treatment with antibiotics fails repeatedly. Our study describes retrospective cohort treated with FMT at two major hospitals in Stockholm.<br><br>METHODS: Medical records of all patients with recurrent CDI treated with FMT during the period 2013-2017 were reviewed. We evaluated cure of CDI-related diarrhea without relapse 10&#x2009;weeks after FMT.<br><br>RESULTS: 47 patients were included. One treatment cured 25 patients (53%), and more than one treatment cured 32 patients (68%). Treatment outcome did not vary significantly with treatment with fresh donor feces or frozen fecal culture, days of use of antibiotics or days of hospitalization prior to CDI, and renal function or time from the first CDI to therapy. Treatment failure was associated with a significantly lower Karnofsky performance status score (70 points vs 90, p=0.02).<br><br>CONCLUSION: Fecal instillation, for the treatment of relapsing CDI, is a promising approach, with 68% success rate reported in this study. The success rate of FMT is high, regardless of multiple comorbidities, extended use of antibiotics, or long time hospitalization. Although generally FMT is performed with fresh donor feces, our data show that the usage of frozen fecal culture could be an effective treatment alternative in recurrent CDI.}, }
@article {pmid31354670, year = {2019}, author = {Metzler-Zebeli, BU and Siegerstetter, SC and Magowan, E and Lawlor, PG and O Connell, NE and Zebeli, Q}, title = {Fecal Microbiota Transplant From Highly Feed Efficient Donors Affects Cecal Physiology and Microbiota in Low- and High-Feed Efficient Chickens.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1576}, pmid = {31354670}, issn = {1664-302X}, abstract = {Fecal microbiota transplants (FMT) may be used to improve chicken's feed efficiency (FE) via modulation of the intestinal microbiota and microbe-host signaling. This study investigated the effect of the administration of FMT from highly feed efficient donors early in life on the jejunal and cecal microbiota, visceral organ size, intestinal morphology, permeability, and expression of genes for nutrient transporters, barrier function and innate immune response in chickens of diverging residual feed intake (RFI; a metric for FE). Chicks (n = 110) were inoculated with the FMT or control transplant (CT) on 1, 6, and 9 days posthatch (dph), from which 56 chickens were selected on 30 dph as the extremes in RFI, resulting in 15 low and 13 high RFI chickens receiving the FMT and 14 low and 14 high RFI chickens receiving the CT. RFI rank and FMT only caused tendencies for alterations in the jejunal microbiota and only one unclassified Lachnospiraceae genus in cecal digesta was indicative of high RFI. By contrast, the FMT caused clear differences in the short-chain fatty acid (SCFA) profile in the crop and cecal microbiota composition compared to the CT, which indicated alterations in amylolytic, pullulanolytic and hemicellulolytic bacteria such as Lactobacillus, Dorea, and Ruminococcus. Moreover, the FMT caused alterations in intestinal development as indicated by the longer duodenum and shallower crypts in the ceca. From the observed RFI-associated variation, energy-saving mechanisms and moderation of the mucosal immune response were indicated by higher jejunal permeability, shorter villi in the ileum, and enhanced cecal expression of the anti-inflammatory cytokine IL10 in low RFI chickens. Relationships obtained from supervised multigroup data integration support that certain bacteria, including Ruminococcocaceae-, Lactobacillus-, and unclassified Clostridiales-phylotypes, and SCFA in jejunal and cecal digesta modulated expression levels of cytokines, tight-junction protein OCLN and nutrient transporters for glucose and SCFA uptake. In conclusion, results suggest that the intestine only played a moderate role for the RFI-associated variation of the present low and high RFI phenotypes, whereas modulating the early microbial colonization resulted in long-lasting changes in bacterial taxonomic and metabolite composition as well as in host intestinal development.}, }
@article {pmid31347341, year = {2019}, author = {Newman, KM and Vaughn, BP}, title = {Efficacy of intestinal microbiota transplantation in ulcerative colitis: a review of current literature and knowledge.}, journal = {Minerva gastroenterologica e dietologica}, volume = {65}, number = {4}, pages = {268-279}, doi = {10.23736/S1121-421X.19.02610-2}, pmid = {31347341}, issn = {1827-1642}, mesh = {Colitis, Ulcerative/*therapy ; *Fecal Microbiota Transplantation ; Forecasting ; Humans ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease (IBD) results in chronic inflammation in the intestine and is thought to arise from an abnormal immune response to host commensal bacteria. The current treatment paradigm for IBD is focused on suppression of the immune system. However, intestinal microbiota transplant (IMT) may present an avenue to treat IBD by altering the target of inflammation without necessitating immune suppression. Presently, reports of the greatest success with IMT in IBD have been with ulcerative colitis (UC). Four randomized controlled trials have evaluated the efficacy of IMT in UC and reported a pooled rate of combined clinical and endoscopic remission of 28% (95% CI: 4-10). For clinical remission alone, the pooled rate was as high as 42% with a number needed to treat of 5 (95% CI: 3-17). While promising, many questions remain which include elucidating the optimal microbiota enrichment, exacting donor profiling, and identifying the optimal IMT route and frequency. Longer follow-up is needed to determine the ability to achieve stable engraftment for maintenance of remission as well as safety of IMT therapeutics. This review will critically appraise the current literature for IMT in UC and identify key knowledge gaps.}, }
@article {pmid31346695, year = {2019}, author = {Madadi-Sanjani, O and Blaser, J and Voigt, G and Kuebler, JF and Petersen, C}, title = {Home-based color card screening for biliary atresia: the first steps for implementation of a nationwide newborn screening in Germany.}, journal = {Pediatric surgery international}, volume = {35}, number = {11}, pages = {1217-1222}, pmid = {31346695}, issn = {1437-9813}, mesh = {Ambulatory Care Facilities ; Biliary Atresia/*diagnosis ; *Color ; *Feces ; Female ; Germany ; Health Policy ; Hospitals, Maternity ; Humans ; Infant ; Infant, Newborn ; Male ; *Neonatal Screening ; Practice Patterns, Physicians'/statistics &amp; numerical data ; }, abstract = {INTRODUCTION: Biliary atresia is a rare neonatal disease and the most common indication for pediatric liver transplantation. Kasai portoenterostomy is the initial treatment, aiming to prevent liver transplantation. Beyond age at Kasai, few prognostic factors are known. Multiple countries have established screening methods to reduce the age at Kasai and recent analysis shows significant better outcomes for screening cohorts. In 2016, we established a decentralized stool color card screening in Lower Saxony and we present our first 2 years of experiences.<br><br>METHODS: In cooperation with a major German health insurance company and the Medical Association of Lower Saxony, we established the screening project, printed 120,000 color cards, and distributed them to all maternity hospitals. Program advertises were printed in newspapers and medical journals. After the first year, the project was evaluated. Thirty maternity hospitals and local practitioners were contacted via telephone, Internet, intranet, and pediatric journals.<br><br>RESULTS: One out of seventy-six maternity hospitals (1.3%) refused to participate in the screening. 30 hospitals (40%) were contacted and 93.5% of the interviewed staff reported that stool color cards were handed out regularly and discussed with the parents. Only 20% of local practitioners assessed neonatal cholestasis to be a relevant problem during daily practice, and 55% regarded a stool color card screening to be useful.<br><br>CONCLUSIONS: In the second year, we extended the screening project to outpatient maternity clinics. Based on the responses of local practitioners, we regard the voluntary screening as insufficient and we have contacted the Federal Joint Committee for the initiation of a nationwide obligatory stool color card screening.}, }
@article {pmid31344423, year = {2019}, author = {Dey, P}, title = {Gut microbiota in phytopharmacology: A comprehensive overview of concepts, reciprocal interactions, biotransformations and mode of actions.}, journal = {Pharmacological research}, volume = {147}, number = {}, pages = {104367}, doi = {10.1016/j.phrs.2019.104367}, pmid = {31344423}, issn = {1096-1186}, mesh = {Animals ; Biotransformation ; Diet ; Gastrointestinal Microbiome/*drug effects ; Humans ; Phytochemicals/pharmacokinetics/*pharmacology ; *Phytotherapy ; }, abstract = {The dynamic and delicate interactions amongst intestinal microbiota, metabolome and metabolism dictates human health and disease. In recent years, our understanding of gut microbial regulation of intestinal immunometabolic and redox homeostasis have evolved mainly out of in vivo studies associated with high-fat feeding induced metabolic diseases. Techniques utilizing fecal transplantation and germ-free mice have been instrumental in reproducibly demonstrating how the gut microbiota affects disease pathogenesis. However, the pillars of modern drug discovery i.e. evidence-based pharmacological studies critically lack focus on intestinal microflora. This is primarily due to targeted in vitro molecular-approaches at cellular-level that largely overlook the etiology of disease pathogenesis from the physiological perspective. Thus, this review aims to provide a comprehensive understanding of the key notions of intestinal microbiota and dysbiosis, and highlight the microbiota-phytochemical bidirectional interactions that affects bioavailability and bioactivity of parent phytochemicals and their metabolites. Potentially by focusing on the three major aspects of gut microbiota i.e. microbial abundance, diversity, and functions, I will discuss phytochemical-microbiota reciprocal interactions, biotransformation of phytochemicals and plant-derived drugs, and pre-clinical and clinical efficacies of herbal medicine on dysbiosis. Additionally, in relation to phytochemical pharmacology, I will briefly discuss the role of dietary-patterns associated with changes in microbial profiles and review pharmacological study models considering possible microbial effects. This review therefore, emphasize on the timely and critically needed evidence-based phytochemical studies focusing on gut microbiota and will provide newer insights for future pre-clinical and clinical phytopharmacological interventions.}, }
@article {pmid31343677, year = {2020}, author = {Lagier, JC and Million, M and Raoult, D}, title = {Bouillabaisse or Fish Soup: The Limitations of Meta-analysis Confronted to the Inconsistency of Fecal Microbiota Transplantation Studies.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {70}, number = {11}, pages = {2454}, doi = {10.1093/cid/ciz707}, pmid = {31343677}, issn = {1537-6591}, mesh = {Animals ; *Clostridioides difficile ; Diagnostic Tests, Routine ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid31343673, year = {2020}, author = {Tariq, R and Pardi, DS and Khanna, S}, title = {Reply to Lagier et al.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {70}, number = {11}, pages = {2454-2455}, doi = {10.1093/cid/ciz708}, pmid = {31343673}, issn = {1537-6591}, mesh = {*Clostridioides difficile ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid31340904, year = {2022}, author = {Castillo-Álvarez, F and Marzo-Sola, ME}, title = {Role of the gut microbiota in the development of various neurological diseases.}, journal = {Neurologia}, volume = {37}, number = {6}, pages = {492-498}, doi = {10.1016/j.nrl.2019.03.017}, pmid = {31340904}, issn = {2173-5808}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Parkinson Disease/pathology ; *Alzheimer Disease ; *Neuromyelitis Optica ; *Amyotrophic Lateral Sclerosis ; *Multiple Sclerosis ; }, abstract = {INTRODUCTION: In recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined.<br><br>DEVELOPMENT: We review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson's disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis.<br><br>CONCLUSIONS: The body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson's disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids. Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation.}, }
@article {pmid31338570, year = {2019}, author = {Turki, AT and Bayraktar, E and Basu, O and Benkö, T and Yi, JH and Kehrmann, J and Tzalavras, A and Liebregts, T and Beelen, DW and Steckel, NK}, title = {Ileostomy for steroid-resistant acute graft-versus-host disease of the gastrointestinal tract.}, journal = {Annals of hematology}, volume = {98}, number = {10}, pages = {2407-2419}, pmid = {31338570}, issn = {1432-0584}, mesh = {Acute Disease ; Adolescent ; Adult ; Child ; Child, Preschool ; *Drug Resistance ; Female ; Gastrointestinal Diseases/microbiology/mortality/surgery ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/microbiology/mortality/surgery ; Hematologic Neoplasms/microbiology/mortality/therapy ; Humans ; *Ileostomy ; Male ; Middle Aged ; Retrospective Studies ; Steroids/administration &amp; dosage ; }, abstract = {Steroid-resistant acute graft-versus-host disease (GVHD) of the gastrointestinal tract associates with important morbidity and mortality. While high-dose steroids are the established first-line therapy in GVHD, no second-line therapy is generally accepted. In this analysis of 65 consecutive patients with severe, steroid-resistant, intestinal GVHD (92% stage 4), additional ileostomy surgery significantly reduced overall mortality (hazard ratio 0.54; 95% confidence interval, 0.36-0.81; p = 0.003) compared to conventional GVHD therapy. Median overall survival was 16 months in the ileostomy cohort compared to 4 months in the conventional therapy cohort. In the ileostomy cohort, both infectious- and GVHD-associated mortality were reduced (40% versus 77%). Significantly declined fecal volumes (p = 0.001) after surgery provide evidence of intestinal adaptation following ileostomy. Correlative studies indicated ileostomy-induced immune-modulation with a > 50% decrease of activated T cells (p = 0.04) and an increase in regulatory T cells. The observed alterations of the patients' gut microbiota may also contribute to ileostomy's therapeutic effect. These data show that ileostomy induced significant clinical responses in patients with steroid-resistant GVHD along with a reduction of pro-inflammatory immune cells and changes of the intestinal microbiota. Ileostomy is a treatment option for steroid-resistant acute GVHD of the gastrointestinal tract that needs further validation in a prospective clinical trial.}, }
@article {pmid31337894, year = {2019}, author = {}, title = {Faecal quality control.}, journal = {Nature microbiology}, volume = {4}, number = {8}, pages = {1243}, doi = {10.1038/s41564-019-0535-1}, pmid = {31337894}, issn = {2058-5276}, mesh = {Clostridiales ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome ; Humans ; *Quality Control ; }, }
@article {pmid31337728, year = {2019}, author = {Staley, C and Kaiser, T and Vaughn, BP and Graiziger, C and Hamilton, MJ and Kabage, AJ and Khoruts, A and Sadowsky, MJ}, title = {Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat Clostridium difficile Infection.}, journal = {mBio}, volume = {10}, number = {4}, pages = {}, pmid = {31337728}, issn = {2150-7511}, support = {R21 AI114722/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteroidetes/classification ; Bayes Theorem ; Clostridioides difficile/pathogenicity ; Clostridium Infections/microbiology/*therapy ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Freezing ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Metformin/therapeutic use ; Microbiota ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Specimen Handling ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has become a common rescue therapy for recurrent Clostridium difficile infection, and encapsulated delivery (cFMT) of healthy donor microbiota shows similar clinical efficacy as more traditional routes of administration. In this study, we characterized long-term patterns of bacterial engraftment in a cohort of 18 patients, who received capsules from one of three donors, up to 409 days post-FMT. Bacterial communities were characterized using Illumina sequencing of the V5-V6 hypervariable regions of the 16S rRNA gene, and engraftment was determined by using the Bayesian algorithm SourceTracker. All patients recovered clinically and were free of C. difficile infection following cFMT. The majority of patients (61%) showed high levels of engraftment after the first week following FMT, which were sustained throughout the year. A small subset, 22%, experienced a decline in donor engraftment after approximately 1 month, and a few patients (17%), two of whom were taking metformin, showed delayed and low levels of donor engraftment. Members of the genera Bacteroides, Parabacteroides, and Faecalibacterium were significantly and positively correlated with donor similarity (ρ = 0.237 to 0.373, P ≤ 0.017). Furthermore, throughout the year, patient fecal communities showed significant separation based on the donor fecal microbiota that they received (P < 0.001). Results of this study, which characterize long-term engraftment following cFMT, suggest that numerical donor similarity is not strictly related to clinical outcome and identify a persistent donor-specific effect on patient fecal microbial communities. Furthermore, results suggest that members of the Bacteroidetes may be important targets to improve engraftment via cFMT.IMPORTANCE Recurrent Clostridium difficile infection (rCDI) is the most common cause of hospital- and community-acquired diarrheal infection associated with antibiotic use. Fecal microbiota transplantation (FMT), a treatment that involves administration of fecal bacteria from a healthy donor to a recipient patient, is a highly effective rescue therapy for rCDI that is increasingly being incorporated into standard clinical practice. Encapsulated, freeze-dried preparations of fecal microbiota, administered orally, offer the simplest and most convenient route of FMT delivery for patients (cFMT). In this study, we evaluated the extent of bacterial engraftment following cFMT and the duration of donor bacterial persistence. All patients studied recovered clinically but showed differing patterns in long-term microbial community similarity to the donor that were associated with members of the bacterial group Bacteroidetes, previously shown to be prominent contributors to rCDI resistance. Results highlight long-lasting, donor-specific effects on recipient patient microbiota and reveal potential bacterial targets to improve cFMT engraftment.}, }
@article {pmid31333622, year = {2019}, author = {Lu, HF and Ren, ZG and Li, A and Zhang, H and Xu, SY and Jiang, JW and Zhou, L and Ling, Q and Wang, BH and Cui, GY and Chen, XH and Zheng, SS and Li, LJ}, title = {Fecal Microbiome Data Distinguish Liver Recipients With Normal and Abnormal Liver Function From Healthy Controls.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1518}, pmid = {31333622}, issn = {1664-302X}, abstract = {Emerging evidence suggests that altered intestinal microbiota plays an important role in the pathogenesis of many liver diseases, mainly by promoting inflammation via the "intestinal microbiota-immunity-liver" axis. We aimed to investigate the fecal microbiome of liver recipients with abnormal/normal liver function using 16S rRNA gene sequencing. Fecal samples were collected from 90 liver recipients [42 with abnormal liver function (Group LT_A) and 48 with normal liver function (Group LT_N)] and 61 age- and gender-matched healthy controls (HCs). Fecal microbiomes were analyzed for comparative composition, diversity, and richness of microbial communities. Principal coordinates analysis successfully distinguished the fecal microbiomes of recipients in Group LT_A from healthy subjects, with the significant decrease of fecal microbiome diversity in recipients in Group LT_A. Other than a higher relative abundance of opportunistic pathogens such as Klebsiella and Escherichia/Shigella in all liver recipients, the main difference in gut microbiome composition between liver recipients and HC was the lower relative abundance of beneficial butyrate-producing bacteria in the recipients. Importantly, we established a fecal microbiome index (specific alterations in Staphylococcus and Prevotella) that could be used to distinguish Group LT_A from Group LT_N, with an area under the receiver operating characteristic curve value of 0.801 and sensitivity and specificity values of 0.771 and 0.786, respectively. These findings revealed unique gut microbial characteristics of liver recipients with abnormal and normal liver functions, and identified fecal microbial risk indicators of abnormal liver function in liver recipients.}, }
@article {pmid31332392, year = {2019}, author = {Qi, X and Yun, C and Sun, L and Xia, J and Wu, Q and Wang, Y and Wang, L and Zhang, Y and Liang, X and Wang, L and Gonzalez, FJ and Patterson, AD and Liu, H and Mu, L and Zhou, Z and Zhao, Y and Li, R and Liu, P and Zhong, C and Pang, Y and Jiang, C and Qiao, J}, title = {Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome.}, journal = {Nature medicine}, volume = {25}, number = {8}, pages = {1225-1233}, pmid = {31332392}, issn = {1546-170X}, support = {ZIA BC005562/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Bile Acids and Salts/*metabolism ; Female ; GATA3 Transcription Factor/*physiology ; *Gastrointestinal Microbiome ; Humans ; Inflammation/complications ; Insulin Resistance ; Interleukins/*physiology ; Mice ; Mice, Inbred C57BL ; Ovary/physiopathology ; Polycystic Ovary Syndrome/*etiology/physiopathology ; Interleukin-22 ; }, abstract = {Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries[1], and is often accompanied by insulin resistance[2]. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity[3,4]. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.}, }
@article {pmid31332389, year = {2019}, author = {Bárcena, C and Valdés-Mas, R and Mayoral, P and Garabaya, C and Durand, S and Rodríguez, F and Fernández-García, MT and Salazar, N and Nogacka, AM and Garatachea, N and Bossut, N and Aprahamian, F and Lucia, A and Kroemer, G and Freije, JMP and Quirós, PM and López-Otín, C}, title = {Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice.}, journal = {Nature medicine}, volume = {25}, number = {8}, pages = {1234-1242}, pmid = {31332389}, issn = {1546-170X}, mesh = {Animals ; Disease Models, Animal ; Dysbiosis ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; *Longevity ; Male ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Progeria/*therapy ; }, abstract = {The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways[1,2]. Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease and cancer[3-6], but its precise role in aging remains to be elucidated. Here, we find that two different mouse models of progeria are characterized by intestinal dysbiosis with alterations that include an increase in the abundance of Proteobacteria and Cyanobacteria, and a decrease in the abundance of Verrucomicrobia. Consistent with these findings, we found that human progeria patients also display intestinal dysbiosis and that long-lived humans (that is, centenarians) exhibit a substantial increase in Verrucomicrobia and a reduction in Proteobacteria. Fecal microbiota transplantation from wild-type mice enhanced healthspan and lifespan in both progeroid mouse models, and transplantation with the verrucomicrobia Akkermansia muciniphila was sufficient to exert beneficial effects. Moreover, metabolomic analysis of ileal content points to the restoration of secondary bile acids as a possible mechanism for the beneficial effects of reestablishing a healthy microbiome. Our results demonstrate that correction of the accelerated aging-associated intestinal dysbiosis is beneficial, suggesting the existence of a link between aging and the gut microbiota that provides a rationale for microbiome-based interventions against age-related diseases.}, }
@article {pmid31329635, year = {2019}, author = {Suwandi, A and Galeev, A and Riedel, R and Sharma, S and Seeger, K and Sterzenbach, T and García Pastor, L and Boyle, EC and Gal-Mor, O and Hensel, M and Casadesús, J and Baines, JF and Grassl, GA}, title = {Std fimbriae-fucose interaction increases Salmonella-induced intestinal inflammation and prolongs colonization.}, journal = {PLoS pathogens}, volume = {15}, number = {7}, pages = {e1007915}, pmid = {31329635}, issn = {1553-7374}, mesh = {Animals ; Bacterial Adhesion ; Colitis/etiology/metabolism/microbiology ; Female ; Fimbriae Proteins/genetics/metabolism ; Fimbriae, Bacterial/genetics/*metabolism ; Fucose/*metabolism ; Fucosyltransferases/deficiency/genetics/metabolism ; Host Microbial Interactions ; Humans ; Intestinal Mucosa/metabolism/microbiology/pathology ; Male ; Mice ; Mice, Inbred CBA ; Mice, Knockout ; Operon ; Salmonella Infections, Animal/etiology/metabolism/microbiology ; Salmonella typhimurium/genetics/*pathogenicity/physiology ; Galactoside 2-alpha-L-fucosyltransferase ; }, abstract = {Expression of ABO and Lewis histo-blood group antigens by the gastrointestinal epithelium is governed by an α-1,2-fucosyltransferase enzyme encoded by the Fut2 gene. Alterations in mucin glycosylation have been associated with susceptibility to various bacterial and viral infections. Salmonella enterica serovar Typhimurium is a food-borne pathogen and a major cause of gastroenteritis. In order to determine the role of Fut2-dependent glycans in Salmonella-triggered intestinal inflammation, Fut2+/+ and Fut2-/- mice were orally infected with S. Typhimurium and bacterial colonization and intestinal inflammation were analyzed. Bacterial load in the intestine of Fut2-/- mice was significantly lower compared to Fut2+/+ mice. Analysis of histopathological changes revealed significantly lower levels of intestinal inflammation in Fut2-/- mice compared to Fut2+/+ mice and measurement of lipocalin-2 level in feces corroborated histopathological findings. Salmonella express fimbriae that assist in adherence of bacteria to host cells thereby facilitating their invasion. The std fimbrial operon of S. Typhimurium encodes the π-class Std fimbriae which bind terminal α(1,2)-fucose residues. An isogenic mutant of S. Typhimurium lacking Std fimbriae colonized Fut2+/+ and Fut2-/- mice to similar levels and resulted in similar intestinal inflammation. In vitro adhesion assays revealed that bacteria possessing Std fimbriae adhered significantly more to fucosylated cell lines or primary epithelial cells in comparison to cells lacking α(1,2)-fucose. Overall, these results indicate that Salmonella-triggered intestinal inflammation and colonization are dependent on Std-fucose interaction.}, }
@article {pmid31328778, year = {2019}, author = {Pebenito, AM and Liu, M and Nazzal, L and Blaser, MJ}, title = {Development of a Humanized Murine Model for the Study of Oxalobacter formigenes Intestinal Colonization.}, journal = {The Journal of infectious diseases}, volume = {220}, number = {11}, pages = {1848-1858}, pmid = {31328778}, issn = {1537-6613}, support = {U54 DK083908/DK/NIDDK NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carrier State/*microbiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Gram-Negative Bacterial Infections/*microbiology ; Intestines/*microbiology ; Mice, Inbred C57BL ; *Models, Animal ; Oxalobacter formigenes/*growth &amp; development ; }, abstract = {BACKGROUND: Oxalobacter formigenes are bacteria that colonize the human gut and degrade oxalate, a component of most kidney stones. Findings of clinical and epidemiological studies suggest that O. formigenes colonization reduces the risk for kidney stones. We sought to develop murine models to allow investigating O. formigenes in the context of its native human microbiome.<br><br>METHODS: For humanization, we transplanted pooled feces from healthy, noncolonized human donors supplemented with a human O. formigenes strain into recipient mice. We transplanted microbiota into mice that were treated with broad-spectrum antibiotics to suppress their native microbiome, were germ free, or received humanization without pretreatment or received sham gavage (controls).<br><br>RESULTS: All humanized mice were stably colonized with O. formigenes through 8 weeks after gavage, whereas mice receiving sham gavage remained uncolonized (P < .001). Humanization significantly changed the murine intestinal microbial community structure (P < .001), with humanized germ-free and antibiotic-treated groups overlapping in &#x3b2;-diversity. Both germ-free and antibiotic-treated mice had significantly increased numbers of human species compared with sham-gavaged mice (P < .001).<br><br>CONCLUSIONS: Transplanting mice with human feces and O. formigenes introduced new microbial populations resembling the human microbiome, with stable O. formigenes colonization; such models can define optimal O. formigenes strains to facilitate clinical trials.}, }
@article {pmid31327302, year = {2019}, author = {Fujii, Y and Nguyen, TTT and Fujimura, Y and Kameya, N and Nakamura, S and Arakawa, K and Morita, H}, title = {Fecal metabolite of a gnotobiotic mouse transplanted with gut microbiota from a patient with Alzheimer's disease.}, journal = {Bioscience, biotechnology, and biochemistry}, volume = {83}, number = {11}, pages = {2144-2152}, doi = {10.1080/09168451.2019.1644149}, pmid = {31327302}, issn = {1347-6947}, mesh = {Alzheimer Disease/*microbiology ; Animals ; Behavior, Animal ; Disease Models, Animal ; Feces/*chemistry/microbiology ; *Gastrointestinal Microbiome ; *Germ-Free Life ; Humans ; Male ; *Metabolomics ; Mice ; Time Factors ; }, abstract = {Studies of Alzheimer's disease are based on model mice that have been altered by transgenesis and other techniques to elicit pathogenesis. However, changes in the gut microbiota were recently suggested to diminish cognitive function in patients, as well as in model mice. Accordingly, we have created model mice of the human gut microbiota by transplanting germ-free C57BL/6N mice with fecal samples from a healthy volunteer and from an affected patient. These humanized mice were stably colonized and reproduced the bacterial diversity in donors. Remarkably, performance on Object Location Test and Object Recognition Test was significantly reduced in the latter than in the former at 55 weeks of age, suggesting that gut microbiota transplanted from an affected patient affects mouse behavior. In addition, metabolites related to the nervous system, including γ-aminobutyrate, taurine, and valine, were significantly less abundant in the feces of mice transplanted with microbiota from the affected patient.}, }
@article {pmid31327219, year = {2019}, author = {Dutta, SK and Verma, S and Jain, V and Surapaneni, BK and Vinayek, R and Phillips, L and Nair, PP}, title = {Parkinson's Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation.}, journal = {Journal of neurogastroenterology and motility}, volume = {25}, number = {3}, pages = {363-376}, pmid = {31327219}, issn = {2093-0879}, abstract = {The role of the microbiome in health and human disease has emerged at the forefront of medicine in the 21st century. Over the last 2 decades evidence has emerged to suggest that inflammation-derived oxidative damage and cytokine induced toxicity may play a significant role in the neuronal damage associated with Parkinson's disease (PD). Presence of pro-inflammatory cytokines and T cell infiltration has been observed in the brain parenchyma of patients with PD. Furthermore, evidence for inflammatory changes has been reported in the enteric nervous system, the vagus nerve branches and glial cells. The presence of α-synuclein deposits in the post-mortem brain biopsy in patients with PD has further substantiated the role of inflammation in PD. It has been suggested that the α-synuclein misfolding might begin in the gut and spread "prion like" via the vagus nerve into lower brainstem and ultimately to the midbrain; this is known as the Braak hypothesis. It is noteworthy that the presence of gastrointestinal symptoms (constipation, dysphagia, and hypersalivation), altered gut microbiota and leaky gut have been observed in PD patients several years prior to the clinical onset of the disease. These clinical observations have been supported by in vitro studies in mice as well, demonstrating the role of genetic (α-synuclein overexpression) and environmental (gut dysbiosis) factors in the pathogenesis of PD. The restoration of the gut microbiome in patients with PD may alter the clinical progression of PD and this alteration can be accomplished by carefully designed studies using customized probiotics and fecal microbiota transplantation.}, }
@article {pmid31326710, year = {2019}, author = {Tolonen, M and Kuuliala, K and Kuuliala, A and Leppäniemi, A and Kylänpää, ML and Sallinen, V and Puolakkainen, P and Mentula, P}, title = {The Association Between Intra-abdominal View and Systemic Cytokine Response in Complicated Intra-abdominal Infections.}, journal = {The Journal of surgical research}, volume = {244}, number = {}, pages = {436-443}, doi = {10.1016/j.jss.2019.06.081}, pmid = {31326710}, issn = {1095-8673}, mesh = {Aged ; Cytokines/*blood ; Female ; Humans ; Intraabdominal Infections/complications/*immunology ; Male ; Middle Aged ; Prospective Studies ; }, abstract = {BACKGROUND: There is a wide variety of disease severity in patients with complicated intraabdominal infection (cIAI). The prognostic role of intraabdominal view (IAV) was recently studied, and an IAV score was introduced. The aim of this study was to analyze the associations between the preoperative levels of eight relevant circulating cytokines and IAV components, the IAV score, as well as outcome.<br><br>MATERIALS AND METHODS: This was a single-center prospective study. The study cohort consisted of operatively managed adult patients with a cIAI. Preoperative plasma levels of eight cytokines were determined. The operating surgeon filled a form describing IAV. Outcomes analyzed were 30-day mortality and the development of organ dysfunctions requiring intensive care unit admission.<br><br>RESULTS: A total of 131 patients with cIAI were analyzed, 30-day mortality was 9.9% (n&#xa0;=&#xa0;13), and 28 (21.4%) patients had postoperative organ dysfunctions. All components of IAV, the IAV score, and outcomes were associated with various cytokine levels. Interleukin-8 was the most competent marker associating with all the variables assessed in this study: diffuse peritonitis (P&#xa0;<&#xa0;0.001), substantial diffuse redness (P&#xa0;=&#xa0;0.012), substantial diffuse fibrin (P&#xa0;=&#xa0;0.003), fecal or bile as exudate (P&#xa0;=&#xa0;0.001), nonappendiceal source of infection (P&#xa0;<&#xa0;0.001), IAV Score groups (P&#xa0;<&#xa0;0.001), organ dysfunctions (P&#xa0;<&#xa0;0.001), and 30-day mortality (P&#xa0;=&#xa0;0.035).<br><br>CONCLUSIONS: Various cytokines associate with the IAV and outcome. IL-8 showed the best overall performance. The results emphasize the role of the surgeons' perception of the IAV. IAV provides an approximation of the magnitude of the systemic inflammatory response.}, }
@article {pmid31326608, year = {2019}, author = {Kelly, MS and Ward, DV and Severyn, CJ and Arshad, M and Heston, SM and Jenkins, K and Martin, PL and McGill, L and Stokhuyzen, A and Bhattarai, SK and Bucci, V and Seed, PC}, title = {Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplantation Recipients.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {25}, number = {11}, pages = {2274-2280}, pmid = {31326608}, issn = {1523-6536}, support = {R15 AI112985/AI/NIAID NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; U19 AI135964/AI/NIAID NIH HHS/United States ; T32 DK098132/DK/NIDDK NIH HHS/United States ; K23 AI135090/AI/NIAID NIH HHS/United States ; }, mesh = {Allografts ; *Bacteria/classification/genetics/growth &amp; development ; *Bacterial Infections/genetics/microbiology ; Child ; Child, Preschool ; *Drug Resistance, Bacterial ; Female ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Humans ; *Intestinal Mucosa/injuries/microbiology/pathology ; Male ; Prospective Studies ; }, abstract = {The gastrointestinal tract is the predicted reservoir for most bloodstream infections (BSIs) after hematopoietic stem cell transplantation (HSCT). Whole-genome sequencing and comparative genomics have the potential to improve our understanding of the dynamics of gut colonization that precede BSI in HSCT recipients. Within a prospective cohort study of children (age <18 years) undergoing HSCT, 9 subjects met criteria for mucosal barrier injury BSI. We performed whole-genome sequencing of the blood culture isolate and weekly fecal samples preceding the BSI to compare the genetic similarity of BSI isolates to fecal strains. We evaluated temporal associations between antibiotic exposures and the abundances of BSI strains in the gut microbiota and correlated the detection of antibiotic resistance genes with the phenotypic antibiotic resistance of these strains. The median patient age was 2.6 years, and 78% were male. BSIs were caused by Escherichia coli (n = 5), Enterococcus faecium (n = 2), Enterobacter cloacae (n = 1), and Rothia mucilaginosa (n = 1). In the 6 BSI episodes with evaluable comparative genomics, the fecal strains were identical to the blood culture isolate (>99.99% genetic similarity). Gut domination by these strains preceded only 4 of 7 E. coli or E. faecium BSIs by a median of 17 days (range, 6 to 21 days). Increasing abundances of the resulting BSI strains in the gut microbiota were frequently associated with specific antibiotic exposures. E. cloacae and R. mucilaginosa were not highly abundant in fecal samples preceding BSIs caused by these species. The detection of antibiotic resistance genes for β-lactam antibiotics and vancomycin predicted phenotypic resistance in BSI strains. Bacterial strains causing mucosal barrier injury BSI in pediatric HSCT recipients were observed in the gut microbiota before BSI onset, and changes in the abundances of these strains within the gut preceded most BSI episodes. However, frequent sampling of the gut microbiota and sampling of other ecological niches is likely necessary to effectively predict BSI in HSCT recipients.}, }
@article {pmid31326346, year = {2019}, author = {Moayyedi, P}, title = {Faecal microbiota transplantation for IBS: still a long way to go.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {4}, number = {9}, pages = {656-657}, doi = {10.1016/S2468-1253(19)30226-2}, pmid = {31326346}, issn = {2468-1253}, mesh = {Diarrhea ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome ; }, }
@article {pmid31326345, year = {2019}, author = {Aroniadis, OC and Brandt, LJ and Oneto, C and Feuerstadt, P and Sherman, A and Wolkoff, AW and Kassam, Z and Sadovsky, RG and Elliott, RJ and Budree, S and Kim, M and Keller, MJ}, title = {Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {4}, number = {9}, pages = {675-685}, doi = {10.1016/S2468-1253(19)30198-0}, pmid = {31326345}, issn = {2468-1253}, mesh = {Abdominal Pain/etiology ; Adult ; Cross-Over Studies ; Diarrhea/*therapy ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*therapy ; Male ; Middle Aged ; Nausea/etiology ; Severity of Illness Index ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has shown promise in alleviating the symptoms of irritable bowel syndrome (IBS); however, controlled data on this technique are scarce. The aim of this clinical trial was to assess the efficacy of FMT in alleviating diarrhoea-predominant IBS (IBS-D).<br><br>METHODS: We did a double-blind, randomised, placebo-controlled crossover trial in patients aged 18-65 years with moderate-to-severe IBS-D defined by an IBS-Symptom Severity Score (IBS-SSS) of more than 175, recruited from three US centres. Patients were randomly assigned (1:1) in blocks of four with a computer-generated randomisation sequence to receive FMT capsules followed by identical-appearing placebo capsules, or placebo capsules followed by FMT capsules. All participants and study team members were masked to randomisation. An independent staff member assigned the treatments according to consecutive numbers. Patients received either 75 FMT capsules (each capsule contained approximately 0&#xb7;38 g of minimally processed donor stool) or 75 placebo capsules over 3 days (25 capsules per day). All patients crossed over to the alternate treatment at 12 weeks. The primary outcome was difference in IBS-SSS between the groups at 12 weeks. Intention-to-treat analyses were done and all patients who received study drug were included in an adverse events analysis. The trial was terminated during recruitment because results from an interim analysis revealed futility. The study is registered with ClinicalTrials.gov, number NCT02328547.<br><br>FINDINGS: From May 28, 2015, to April 21, 2017, 48 patients were randomly assigned to receive FMT first (n=25) or placebo first (n=23). Three participants were lost to follow-up in the FMT group. IBS-SSS did not differ between FMT recipients (mean 221 [SD 105]) and placebo recipients (236 [95]) at 12 weeks (p=0&#xb7;65), after adjustment for baseline scores. The most common drug-related adverse events included abdominal pain (five [10%] of the 48 participants while receiving FMT capsules vs four [8%] while receiving placebo), nausea (four [8%] vs two [4%]), and exacerbation of diarrhoea (three [6%] vs eight [17%]). One serious adverse event that was unrelated to study drug (acute cholecystitis) was reported in a patient while receiving placebo capsules.<br><br>INTERPRETATION: FMT was safe, but did not induce symptom relief at 12 weeks compared with placebo. Additional studies are needed to determine the efficacy of FMT for IBS-D.<br><br>FUNDING: National Institutes of Health.}, }
@article {pmid31322321, year = {2019}, author = {Petrov, PD and García-Mediavilla, MV and Guzmán, C and Porras, D and Nistal, E and Martínez-Flórez, S and Castell, JV and González-Gallego, J and Sánchez-Campos, S and Jover, R}, title = {A Network Involving Gut Microbiota, Circulating Bile Acids, and Hepatic Metabolism Genes That Protects Against Non-Alcoholic Fatty Liver Disease.}, journal = {Molecular nutrition &amp; food research}, volume = {63}, number = {20}, pages = {e1900487}, doi = {10.1002/mnfr.201900487}, pmid = {31322321}, issn = {1613-4133}, mesh = {Animals ; Bile Acids and Salts/*blood ; Diet, High-Fat ; Ethanol/blood ; *Gastrointestinal Microbiome ; Liver/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/*prevention &amp; control ; Transcriptome ; }, abstract = {SCOPE: Gut microbiota contributes to non-alcoholic fatty liver disease (NAFLD) pathogenesis by multiple mechanisms not yet completely understood. Novel differential features between germ-free mice (GFm) transplanted with protective or non-protective cecal microbiota against NAFLD are investigated.<br><br>METHODS AND RESULTS: Gut microbiota composition, plasma, and fecal bile acids (BAs) and liver mRNAs are quantified in GFm recipients from four donor mice differing in NAFLD severity (control diet, high-fat diet [HFD]-responder, HFD-non-responder, and quercetin-supplemented HFD). Transplanted GFm are on control or HFD for 16-weeks. Multivariate analysis shows that GFm colonized with microbiota from HFD-non-responder and quercetin supplemented-HFD donors (protected against NAFLD) clusters together, whereas GFm colonized with microbiota from control and HFD-responder mice (non-protected against NAFLD) establishes another cluster. Protected phenotype is associated with increased gut Desulfovibrio and Oscillospira, reduced gut Bacteroides and Oribacterium, lower primary and higher secondary BAs in plasma and feces, induction of hepatic BA transporters, and repression of hepatic lipogenic and BA synthesis genes.<br><br>CONCLUSION: Protective gut microbiota associates with increased specific secondary BAs, which likely inhibit lipogenic pathways and enhance bile flow in the liver. This novel cross-talk between gut and liver, via plasma BAs, that promotes protection against NAFLD may have clinical and nutritional relevance.}, }
@article {pmid31319545, year = {2019}, author = {Rodriguez, DM and Benninghoff, AD and Aardema, NDJ and Phatak, S and Hintze, KJ}, title = {Basal Diet Determined Long-Term Composition of the Gut Microbiome and Mouse Phenotype to a Greater Extent than Fecal Microbiome Transfer from Lean or Obese Human Donors.}, journal = {Nutrients}, volume = {11}, number = {7}, pages = {}, pmid = {31319545}, issn = {2072-6643}, support = {A34029 FY15 UAES Grant//Utah Agricultural Experiment Station/ ; }, mesh = {Animal Feed ; Animals ; Bacteria/classification ; Blood Glucose ; Body Composition ; Body Fat Distribution ; Cecum/anatomy &amp; histology ; *Diet ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Glucose Tolerance Test ; Humans ; Liver/anatomy &amp; histology ; Male ; Mice ; Obesity/*microbiology ; Organ Size ; Random Allocation ; Weight Gain ; }, abstract = {The Western dietary pattern can alter the gut microbiome and cause obesity and metabolic disorders. To examine the interactions between diet, the microbiome, and obesity, we transplanted gut microbiota from lean or obese human donors into mice fed one of three diets for 22 weeks: (1) a control AIN93G diet; (2) the total Western diet (TWD), which mimics the American diet; or (3) a 45% high-fat diet-induced obesity (DIO) diet. We hypothesized that a fecal microbiome transfer (FMT) from obese donors would lead to an obese phenotype and aberrant glucose metabolism in recipient mice that would be exacerbated by consumption of the TWD or DIO diets. Prior to the FMT, the native microbiome was depleted using an established broad-spectrum antibiotic protocol. Interestingly, the human donor body type microbiome did not significantly affect final body weight or body composition in mice fed any of the experimental diets. Beta diversity analysis and linear discriminant analysis with effect size (LEfSe) showed that mice that received an FMT from obese donors had a significantly different microbiome compared to mice that received an FMT from lean donors. However, after 22 weeks, diet influenced the microbiome composition irrespective of donor body type, suggesting that diet is a key variable in the shaping of the gut microbiome after FMT.}, }
@article {pmid31316785, year = {2019}, author = {Gutin, L and Piceno, Y and Fadrosh, D and Lynch, K and Zydek, M and Kassam, Z and LaMere, B and Terdiman, J and Ma, A and Somsouk, M and Lynch, S and El-Nachef, N}, title = {Fecal microbiota transplant for Crohn disease: A study evaluating safety, efficacy, and microbiome profile.}, journal = {United European gastroenterology journal}, volume = {7}, number = {6}, pages = {807-814}, pmid = {31316785}, issn = {2050-6406}, mesh = {Adolescent ; Adult ; Aged ; Crohn Disease/etiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Metagenomics/methods ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Emerging trials suggest fecal microbiota transplantation (FMT) is a promising treatment for ulcerative colitis; however, there is a paucity of data in Crohn disease (CD).<br><br>OBJECTIVE: The objectives of this article are to determine whether single-dose FMT improves clinical and endoscopic outcomes in CD patients and to identify meaningful changes in the microbiome in response to FMT.<br><br>METHODS: We performed a prospective, open-label, single-center study. Ten CD patients underwent FMT and were evaluated for clinical response (defined as decrease in Harvey-Bradshaw Index score &#x2265;3 at one month post-FMT) and microbiome profile (16S ribosomal RNA sequencing) at one month post-FMT.<br><br>RESULTS: Three of 10 patients responded to FMT. Two of 10 patients had significant adverse events requiring escalation of therapy. On microbiome analysis, bacterial communities of responders had increased relative abundance of bacteria commonly found in donor gut microbiota.<br><br>CONCLUSIONS: Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm. Responders tended to have lower baseline alpha diversity, suggesting baseline perturbation of microbiota may be an indicator of potential responders to FMT in this patient population. Controlled trials are needed to further assess the efficacy and safety of FMT in CD and determine whether FMT is a viable option in this patient population.Clinicaltrials.gov number: NCT02460705.}, }
@article {pmid31316751, year = {2019}, author = {Lin, DM and Lin, HC}, title = {A theoretical model of temperate phages as mediators of gut microbiome dysbiosis.}, journal = {F1000Research}, volume = {8}, number = {}, pages = {}, pmid = {31316751}, issn = {2046-1402}, mesh = {*Bacteriophages ; *Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Models, Theoretical ; }, abstract = {Bacteriophages are the most prominent members of the gut microbiome, outnumbering their bacterial hosts by a factor of 10. Phages are bacteria-specific viruses that are gaining attention as highly influential regulators of the gut bacterial community. Dysregulation of the gut bacterial community contributes to dysbiosis, a microbiome disorder characterized by compositional and functional changes that contribute to disease. A role for phages in gut microbiome dysbiosis is emerging with evidence that the gut phage community is altered in dysbiosis-associated disorders such as colorectal cancer and inflammatory bowel disease. Several recent studies have linked successful fecal microbiota transplantation to uptake of the donor's gut phage community, offering some insight into why some recipients respond to treatment whereas others do not. Here, we review the literature supporting a role for phages in mediating the gut bacterial community, giving special attention to Western diet dysbiosis as a case study to demonstrate a theoretical phage-based mechanism for the establishment and maintenance of dysbiosis.}, }
@article {pmid31315214, year = {2019}, author = {Shin, JH and Chaplin, AS and Hays, RA and Kolling, GL and Vance, S and Guerrant, RL and Archbald-Pannone, L and Warren, CA}, title = {Outcomes of a Multidisciplinary Clinic in Evaluating Recurrent Clostridioides difficile Infection Patients for Fecal Microbiota Transplant: A Retrospective Cohort Analysis.}, journal = {Journal of clinical medicine}, volume = {8}, number = {7}, pages = {}, pmid = {31315214}, issn = {2077-0383}, support = {5T32AI007046-39//National Institute of Allergy and Infectious Diseases/ ; Buchanan Award//University of Virginia/ ; }, abstract = {Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infections (rCDIs). We assessed the benefits of a multidisciplinary C. difficile clinic for screening FMT eligibility in patients with rCDI. Patients seen at the University of Virginia Complicated C. difficile Clinic (CCDC) underwent comprehensive evaluation for possible FMT. Patients were eligible for FMT if there was history of greater than two episodes of rCDI. Patients were evaluated for the outcome after evaluation in the clinic. A total of 113 patients were evaluated: 77 were eligible for FMT, of which 25 patients did not undergo FMT. The rate of recurrence at three months and all-cause mortality were 4.5% and 7% for patients who received FMT and 16.7% and 12.5% for eligible patients who did not receive FMT. There were 36 patients who were not eligible for FMT, with two or fewer recurrences and a recurrence rate of 8.8% and all-cause mortality of 6%. One in three patients screened for FMT had a nutritional deficiency diagnosed, with zinc deficiency being most common (20%). Additional diagnoses, including inflammatory bowel disease, were made during the evaluation. FMT is a highly effective treatment for rCDI, most notably in patients with multiple recurrences. A systematic approach for evaluating patients with rCDI helps identify patients who benefit most from FMT and those who have other conditions.}, }
@article {pmid31313610, year = {2019}, author = {Catho, G and Huttner, BD}, title = {Strategies for the eradication of extended-spectrum beta-lactamase or carbapenemase-producing Enterobacteriaceae intestinal carriage.}, journal = {Expert review of anti-infective therapy}, volume = {17}, number = {8}, pages = {557-569}, doi = {10.1080/14787210.2019.1645007}, pmid = {31313610}, issn = {1744-8336}, mesh = {Animals ; Anti-Bacterial Agents/*administration &amp; dosage ; Carbapenem-Resistant Enterobacteriaceae/*drug effects/isolation &amp; purification ; Carrier State/microbiology ; Drug Resistance, Multiple, Bacterial ; Enterobacteriaceae Infections/epidemiology/microbiology/*therapy ; Fecal Microbiota Transplantation ; Humans ; Intestines/microbiology ; Probiotics/administration &amp; dosage ; }, abstract = {Introduction: Among the multidrug resistant pathogens, extended-spectrum beta-lactamase (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE) are currently considered the main threat due to the scarcity of therapeutic options and their rapid spread around the globe. In addition to developing new antibiotics and stopping transmission, recent research has focused on 'decolonization' strategies to eradicate the carriage of ESBL-E/CPE before infection occurs. Areas covered: In this narrative review, we aim to describe the current evidence of decolonization strategies for ESBL-E or CPE intestinal carriage. We first define decolonization and highlight the issues related to the lack of standardized definitions, then we summarize the available data on the natural history of colonization. Finally, we review the strategies assessed over the past 10 years for ESBL and CPE decolonization: oral antibiotics, probiotics and more recently fecal microbiota transplantation. We conclude by presenting the risks and uncertainties associated with these strategies. Expert opinion: The evidence available today is too low to recommend decolonization strategies for ESBL-E or CPE in routine clinical practice. The potential increase of resistance and the impact of microbiome manipulation should not be underestimated. Some of these decolonization strategies may nevertheless be effective, at least in temporarily suppressing colonization, which could be useful for specific populations such as high-risk patients. Effectiveness and long-term effects must be properly assessed through well-designed randomized controlled trials.}, }
@article {pmid31311041, year = {2019}, author = {Hintze, G}, title = {[Microbiome - growing importance in medicine].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {144}, number = {14}, pages = {929}, doi = {10.1055/a-0762-3043}, pmid = {31311041}, issn = {1439-4413}, mesh = {Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; }, }
@article {pmid31306634, year = {2019}, author = {Lo, GH}, title = {The Transplantation of Fecal Microbiota for Cirrhotic Patients.}, journal = {Gastroenterology}, volume = {157}, number = {3}, pages = {902}, doi = {10.1053/j.gastro.2019.06.040}, pmid = {31306634}, issn = {1528-0012}, mesh = {Fecal Microbiota Transplantation ; Feces ; Humans ; *Liver Cirrhosis ; *Microbiota ; }, }
@article {pmid31306584, year = {2019}, author = {Fay, KT and Klingensmith, NJ and Chen, CW and Zhang, W and Sun, Y and Morrow, KN and Liang, Z and Burd, EM and Ford, ML and Coopersmith, CM}, title = {The gut microbiome alters immunophenotype and survival from sepsis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {10}, pages = {11258-11269}, pmid = {31306584}, issn = {1530-6860}, support = {R01 GM113228/GM/NIGMS NIH HHS/United States ; R01 GM072808/GM/NIGMS NIH HHS/United States ; R01 GM104323/GM/NIGMS NIH HHS/United States ; T32 GM095442/GM/NIGMS NIH HHS/United States ; R01 GM109779/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; Interferon-gamma/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota/immunology ; Peyer's Patches/immunology ; Sepsis/*immunology/*microbiology ; }, abstract = {The microbiome is increasingly implicated in immune regulation and mortality from sepsis. Mice with identical genetic backgrounds but distinct microbiomes were obtained from different vendors and analyzed following cecal ligation and puncture (CLP). β diversity of the microbiome measured from feces demonstrated significant differences between The Jackson Laboratory (Jax; Bar Harbor, ME, USA) and Charles River Laboratories (CR; Wilmington, MA, USA) C57/B6 mice. Jax mice had 7-d mortality of 90% following CLP, whereas CR mice had a mortality of 53%. Differences in vendor were associated with altered immunophenotype with increased splenic IFN-γ[+]CD4[+] T cells, effector memory CD4[+] T cells, and central memory CD4[+] T cells and increased Peyer's patch effector memory CD4[+] T cells in septic CR mice. To determine whether differences in the microbiome were responsible for these differences, Jax and CR mice were cohoused for 3 wk, after which they assumed a similar microbiota composition. Cohoused mice had improved survival following CLP compared to Jax mice and had similar survival regardless of their vendor of origin. All differences in immunophenotype between septic Jax and CR mice disappeared following cohousing. These findings suggest that the microbiome plays a crucial role in survival and the host immune response from sepsis and represents a potential target for therapeutic intervention.-Fay, K. T., Klingensmith, N. J., Chen, C.-W., Zhang, W., Sun, Y., Morrow, K. N., Liang, Z., Burd, E. M., Ford, M. L., Coopersmith, C. M. The gut microbiome alters immunophenotype and survival from sepsis.}, }
@article {pmid31306229, year = {2019}, author = {Chen, X and Li, HY and Hu, XM and Zhang, Y and Zhang, SY}, title = {Current understanding of gut microbiota alterations and related therapeutic intervention strategies in heart failure.}, journal = {Chinese medical journal}, volume = {132}, number = {15}, pages = {1843-1855}, pmid = {31306229}, issn = {2542-5641}, mesh = {Dysbiosis/microbiology/therapy ; Gastrointestinal Microbiome/*physiology ; Heart Failure/*microbiology/*therapy ; Humans ; Microbiota/physiology ; }, abstract = {OBJECTIVE: The purpose of this review is to stress the complicated interactions between the microbiota and the development of heart failure. Moreover, the feasibility of modulating intestinal microbes and metabolites as novel therapeutic strategies is discussed.<br><br>DATA SOURCES: This study was based on data obtained from PubMed up to March 31, 2019. Articles were selected using the following search terms: "gut microbiota," "heart failure," "trimethylamine N-oxide (TMAO)," "short-chain fatty acid (SCFA)," "bile acid," "uremic toxin," "treatment," "diet," "probiotic," "prebiotic," "antibiotic," and "fecal microbiota transplantation."<br><br>RESULTS: Accumulated evidence has revealed that the composition of the gut microbiota varies obviously in people with heart failure compared to those with healthy status. Altered gut microbial communities contribute to heart failure through bacterial translocation or affecting multiple metabolic pathways, including the trimethylamine/TMAO, SCFA, bile acid, and uremic toxin pathways. Meanwhile, modulation of the gut microbiota through diet, pre/probiotics, fecal transplantation, and microbial enzyme inhibitors has become a potential therapeutic approach for many metabolic disorders. Specifically, a few studies have focused on the cardioprotective effects of probiotics on heart failure.<br><br>CONCLUSIONS: The composition of the gut microbiota in people with heart failure is different from those with healthy status. A reduction in SCFA-producing bacteria in patients with heart failure might be a notable characteristic for patients with heart failure. Moreover, an increase in the microbial potential to produce TMAO and lipopolysaccharides is prominent. More researches focused on the mechanisms of microbial metabolites and the clinical application of multiple therapeutic interventions is necessarily required.}, }
@article {pmid31306151, year = {2019}, author = {Allegretti, JR and Kassam, Z}, title = {Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: The Next Steps in This Promising Story.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {8}, pages = {1354-1355}, doi = {10.14309/ajg.0000000000000317}, pmid = {31306151}, issn = {1572-0241}, mesh = {*Cholangitis, Sclerosing ; Fecal Microbiota Transplantation ; Humans ; *Liver Transplantation ; Recurrence ; }, }
@article {pmid31305466, year = {2019}, author = {Sun, L and Li, J and Lan, LL and Li, XA}, title = {The effect of fecal microbiota transplantation on Hepatic myelopathy: A case report.}, journal = {Medicine}, volume = {98}, number = {28}, pages = {e16430}, pmid = {31305466}, issn = {1536-5964}, mesh = {End Stage Liver Disease/*therapy ; *Fecal Microbiota Transplantation ; Female ; Hepatitis B/therapy ; Humans ; Liver Cirrhosis/therapy ; Middle Aged ; Paresis/therapy ; Spinal Cord Diseases/*therapy ; Treatment Outcome ; }, abstract = {RATIONALE: Hepatic myelopathy (HM), also known as portal-systemic myelopathy, is a rare neurological complication that occurs in patients with chronic liver disease. There is no easy and feasible treatment, liver transplantation is the only accepted therapy that may be effective for patients at early stage at present. The pathogenesis of the disease is not clear yet, and the prognosis is poor. Here we describe a reversible HM after fecal microbiota transplantation.<br><br>PATIENT CONCERNS: In this report, a middle-aged female patient with hepatitis B cirrhosis, occurred HM after transjugular intrahepatic portosystemic shunt, a progressive spastic paraparesis in both legs were the main symptoms.<br><br>DIAGNOSIS: The patient was diagnosed with HM.<br><br>INTERVENTIONS: The patient received 3 times of fecal microbiota transplantations (FMT).<br><br>OUTCOMES: The patient's muscle strength of both legs were increased at various degrees, the patient's condition improved from HM2 to HM1.<br><br>LESSONS: FMT may be another effective way to treat HM. It is cheaper, more operable, and simpler than the approved treatment and worthy of further research.}, }
@article {pmid31304425, year = {2019}, author = {Borody, TJ and Clancy, A}, title = {Fecal microbiota transplantation for ulcerative colitis-where to from here?.}, journal = {Translational gastroenterology and hepatology}, volume = {4}, number = {}, pages = {48}, pmid = {31304425}, issn = {2415-1289}, }
@article {pmid31304012, year = {2019}, author = {Canibe, N and O'Dea, M and Abraham, S}, title = {Potential relevance of pig gut content transplantation for production and research.}, journal = {Journal of animal science and biotechnology}, volume = {10}, number = {}, pages = {55}, pmid = {31304012}, issn = {1674-9782}, abstract = {It is becoming increasingly evident that the gastrointestinal microbiota has a significant impact on the overall health and production of the pig. This has led to intensified research on the composition of the gastrointestinal microbiota, factors affecting it, and the impact of the microbiota on health, growth performance, and more recently, behavior of the host. Swine production research has been heavily focused on assessing the effects of feed additives and dietary modifications to alter or take advantage of select characteristics of gastrointestinal microbes to improve health and feed conversion efficiency. Research on faecal microbiota transplantation (FMT) as a possible tool to improve outcomes in pigs through manipulation of the gastrointestinal microbiome is very recent and limited data is available. Results on FMT in humans demonstrating the transfer of phenotypic traits from donors to recipients and the high efficacy of FMT to treat Clostridium difficile infections in humans, together with data from pigs relating GI-tract microbiota composition with growth performance has likely played an important role in the interest towards this strategy in pig production. However, several factors can influence the impact of FMT on the recipient, and these need to be identified and optimized before this tool can be applied to pig production. There are obvious inherent biosecurity and regulatory issues in this strategy, since the donor's microbiome can never be completely screened for all possible non-desirable microorganisms. However, considering the success observed in humans, it seems worth investigating this strategy for certain applications in pig production. Further, FMT research may lead to the identification of specific bacterial group(s) essential for a particular outcome, resulting in the development of banks of clones which can be used as targeted therapeutics, rather than the broader approach applied in FMT. This review examines the factors associated with the use of FMT, and its potential application to swine production, and includes research on using the pig as model for human medical purposes.}, }
@article {pmid31303182, year = {2019}, author = {Dubey, JP and Almeria, S}, title = {Cystoisospora belli infections in humans: the past 100 years.}, journal = {Parasitology}, volume = {146}, number = {12}, pages = {1490-1527}, doi = {10.1017/S0031182019000957}, pmid = {31303182}, issn = {1469-8161}, mesh = {*Coccidiosis/diagnosis/epidemiology/parasitology/prevention &amp; control ; Humans ; Life History Traits ; Prevalence ; *Sarcocystidae/cytology/growth &amp; development ; }, abstract = {Cystoisospora belli is a coccidian parasite of humans, with a direct fecal-oral transmission cycle. It is globally distributed, but mainly found in tropical and subtropical areas. Many cases of C. belli infections have been reported in patients with HIV, and in patients undergoing immunosuppressive therapy for organ transplants or those treated for tumours worldwide. Unsporulated or partially sporulated oocysts of C. belli are excreted in feces. When sporulated oocysts in contaminated water or food are ingested, asexual and sexual stages of C. belli are confined to the epithelium of intestines, bile ducts and gallbladder. Monozoic tissue cysts are present in extra-intestinal organs (lamina propria of the small and large intestine, lymph nodes, spleen, and liver) of immunosuppressed humans. However, a paratenic host has not been demonstrated. Cystoisospora belli infections can be persistent, lasting for months, and relapses are common; the mechanism of relapse is unknown. Recently, the endogenous stages of C. belli were re-examined and attention was drawn to cases of misidentification of non-protozoal structures in the gallbladder of patients as C. belli. Here, we review all aspects of the biology of C. belli, including morphology, endogenous stages, prevalence, epidemiology, symptoms, diagnosis and control.}, }
@article {pmid31302808, year = {2020}, author = {Selvig, D and Piceno, Y and Terdiman, J and Zydek, M and Umetsu, SE and Balitzer, D and Fadrosh, D and Lynch, K and Lamere, B and Leith, T and Kassam, Z and Beck, K and Lewin, S and Ma, A and Somsouk, M and Lynch, SV and El-Nachef, N}, title = {Fecal Microbiota Transplantation in Pouchitis: Clinical, Endoscopic, Histologic, and Microbiota Results from a Pilot Study.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {4}, pages = {1099-1106}, pmid = {31302808}, issn = {1573-2568}, mesh = {Adolescent ; Adult ; Aged ; Endoscopy, Gastrointestinal/*methods ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Middle Aged ; Pilot Projects ; Pouchitis/*diagnosis/microbiology/*therapy ; Prospective Studies ; Young Adult ; }, abstract = {AIMS: This pilot study assessed the efficacy, safety, and microbiome dynamics of fecal microbiota transplantation (FMT) for patients with chronic pouchitis.<br><br>METHODS: A prospective open-label pilot study was performed at an academic center among pouchitis patients undergoing FMT. Patients received a minimum of a single FMT by pouchoscopy from healthy, screened donors. The primary outcome was clinical improvement in pouchitis assessed by patient survey at week 4. Secondary outcomes included decrease in total Pouchitis Disease Activity Index (PDAI) Score&#x2009;&#x2265;&#x2009;3 at week 4, bowel movement frequency, ESR, CRP, fecal calprotectin, abdominal pain, and PDAI subscores including endoscopic and histologic changes. Stool samples were collected at baseline and 4&#xa0;weeks post-FMT to assess bacterial microbiota using V4 16S rRNA sequencing.<br><br>RESULTS: Nineteen patients were enrolled; however, 1 patient was lost to follow-up. No patients had a major adverse event or escalation of therapy related to FMT. Total PDAI scores, endoscopic scores, and histologic scores did not decrease significantly post-FMT. However, there was a statistically significant improvement in bowel movement (BM) frequency (9.25-7.25&#xa0;BM/day, p&#x2009;=&#x2009;0.03) and trend for improvement in abdominal pain to improve post-FMT (p&#x2009;=&#x2009;0.05). Bacterial microbiota profiling revealed no distinct community-level changes post-FMT, though a small number of specific bacterial taxa significantly differed in relative abundance.<br><br>CONCLUSIONS: A single FMT has a tolerable short-term safety profile and may be associated with a decrease in bowel movements in patients with chronic pouchitis; however, no robust endoscopic or histologic changes were observed.}, }
@article {pmid31302141, year = {2019}, author = {Bajaj, JS and Gillevet, PM}, title = {Reply.}, journal = {Gastroenterology}, volume = {157}, number = {3}, pages = {902-903}, doi = {10.1053/j.gastro.2019.07.005}, pmid = {31302141}, issn = {1528-0012}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Liver Cirrhosis ; }, }
@article {pmid31301451, year = {2020}, author = {Allegretti, JR and Kassam, Z and Mullish, BH and Chiang, A and Carrellas, M and Hurtado, J and Marchesi, JR and McDonald, JAK and Pechlivanis, A and Barker, GF and Miguéns Blanco, J and Garcia-Perez, I and Wong, WF and Gerardin, Y and Silverstein, M and Kennedy, K and Thompson, C}, title = {Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {18}, number = {4}, pages = {855-863.e2}, doi = {10.1016/j.cgh.2019.07.006}, pmid = {31301451}, issn = {1542-7714}, support = {21228/VAC_/Versus Arthritis/United Kingdom ; MC_PC_17162/MRC_/Medical Research Council/United Kingdom ; MR/P028225/1/MRC_/Medical Research Council/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Capsules ; *Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Mice ; Obesity/complications/therapy ; Pilot Projects ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Studies in mice have shown that the intestinal microbiota can contribute to obesity via the anorexigenic gut hormone glucagon-like peptide 1 (GLP1) and bile acids, which affect lipid metabolism. We performed a randomized, placebo-controlled, pilot study of the effects of fecal microbiota transplantation (FMT) in obese, metabolically uncompromised patients.<br><br>METHODS: We performed a double-blind study of 22 obese patients (body mass index [BMI] &#x2265;5 kg/m[2]) without a diagnosis of diabetes, nonalcoholic steatohepatitis, or metabolic syndrome. Participants were assigned randomly (1:1) to groups that received FMT by capsules (induction dose of 30 capsules at week 4 and maintenance dose of 12 capsules at week 8) or placebo capsules. FMT capsules were derived from a single lean donor (BMI, 17.5 kg/m[2]). Patients were followed up through week 26; the primary outcome was safety. Stool and serum samples were collected from patients at baseline and at weeks 1, 4, 6, 8, and 12 after administration of the first dose of FMT or placebo and analyzed by 16S RNA gene sequencing. Stool and serum samples were analyzed for metabolomics by liquid chromatography-mass spectrometry. Additional outcomes were the change in area under the curve for GLP1 at week&#xa0;12.<br><br>RESULTS: We observed no significant differences in adverse events between patients who received FMT vs placebo. There was no increase in the area under the curve of GLP1 in either group. Patients who received FMT had sustained shifts in microbiomes associated with obesity toward those of the donor (P < .001). Patients who received FMT had a sustained decrease in stool levels of taurocholic acid (P < .05) compared with baseline; bile acid profiles began to resemble those of the donor more closely. We did not observe significant changes in mean BMI at week 12 in either group.<br><br>CONCLUSIONS: In a placebo-controlled pilot study, we found that FMT capsules (derived from a lean donor) were safe but did not reduce BMI in obese metabolically uncompromised patients. The FMT capsules were well tolerated and led to sustained changes in the intestinal microbiome and bile acid profiles that were similar to those of the lean donor. ClinicalTrials.gov number: NCT02741518.}, }
@article {pmid31297516, year = {2023}, author = {Murphy, CL and Zulquernain, SA and Shanahan, F}, title = {Faecal microbiota transplantation (FMT): classical bedside-to-bench clinical research.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {116}, number = {8}, pages = {641-643}, doi = {10.1093/qjmed/hcz181}, pmid = {31297516}, issn = {1460-2393}, support = {APC/SFI/12/RC/2273/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {Humans ; Fecal Microbiota Transplantation ; Feces ; *Clostridioides difficile ; Treatment Outcome ; *Clostridium Infections ; }, }
@article {pmid31293718, year = {2019}, author = {Campion, D and Giovo, I and Ponzo, P and Saracco, GM and Balzola, F and Alessandria, C}, title = {Dietary approach and gut microbiota modulation for chronic hepatic encephalopathy in cirrhosis.}, journal = {World journal of hepatology}, volume = {11}, number = {6}, pages = {489-512}, pmid = {31293718}, issn = {1948-5182}, abstract = {Hepatic encephalopathy (HE) is a common and serious neuropsychiatric complication of cirrhosis, acute liver failure, and porto-systemic shunting. HE largely contributes to the morbidity of patients with liver disease, severely affecting the quality of life of both patients and their relatives and being associated with poor prognosis. Its presentation is largely variable, manifesting with a broad spectrum of cognitive abnormalities ranging from subtle cognitive impairment to coma. The pathogenesis of HE is complex and has historically been linked with hyperammonemia. However, in the last years, it has become evident that the interplay of multiple actors, such as intestinal dysbiosis, gut hyperpermeability, and neuroinflammation, is of crucial importance in its genesis. Therefore, HE can be considered a result of a dysregulated gut-liver-brain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by "gut-centric" therapies, such as non-absorbable disaccharides, non-absorbable antibiotics, probiotics, prebiotics, and fecal microbiota transplantation. In this context dietary modifications, by modulating the intestinal milieu, can also provide significant benefit to cirrhotic patients with HE. This review will provide a comprehensive insight into the mechanisms responsible for gut-liver-brain axis dysregulation leading to HE in cirrhosis. Furthermore, it will explore the currently available therapies and the most promising future treatments for the management of patients with HE, with a special focus on the dietary approach.}, }
@article {pmid31293562, year = {2019}, author = {Ni, J and Huang, R and Zhou, H and Xu, X and Li, Y and Cao, P and Zhong, K and Ge, M and Chen, X and Hou, B and Yu, M and Peng, B and Li, Q and Zhang, P and Gao, Y}, title = {Analysis of the Relationship Between the Degree of Dysbiosis in Gut Microbiota and Prognosis at Different Stages of Primary Hepatocellular Carcinoma.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1458}, pmid = {31293562}, issn = {1664-302X}, abstract = {Gut microbiota dysbiosis is closely associated with primary hepatocellular carcinoma (HCC). Recent studies have evaluated the early diagnosis of primary HCC through analysis of gut microbiota dysbiosis. However, the relationship between the degree of dysbiosis and the prognosis of primary HCC remains unclear. Because primary HCC is accompanied by dysbiosis and dysbiosis usually increases the circulatory concentrations of endotoxin and other harmful bacterial substances, which further increases liver damage, we hypothesized that level of dysbiosis associated with primary HCC increases with the stage of cancer progression. To test this hypothesis, we introduced a more integrated index referred to as the degree of dysbiosis (Ddys); and we investigated Ddys of the gut microbiota with the development of primary HCC through high-throughput sequencing of 16S rRNA gene amplicons. Our results showed that compared with healthy individuals, patients with primary HCC showed increased pro-inflammatory bacteria in their fecal microbiota. The Ddys increased significantly in patients with primary HCC compared with that in healthy controls. Moreover, there was a tendency for the Ddys to increase with the development of primary HCC, although no significant difference was detected between different stages of primary HCC. Our findings provide important insights into the use of gut microbiota analysis during the treatment of primary HCC.}, }
@article {pmid31291465, year = {2020}, author = {Liu, T and Song, X and Khan, S and Li, Y and Guo, Z and Li, C and Wang, S and Dong, W and Liu, W and Wang, B and Cao, H}, title = {The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing.}, journal = {International journal of cancer}, volume = {146}, number = {7}, pages = {1780-1790}, doi = {10.1002/ijc.32563}, pmid = {31291465}, issn = {1097-0215}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Biological Therapy ; Biomarkers ; Cell Transformation, Neoplastic/*metabolism ; Colorectal Neoplasms/etiology/metabolism/pathology/therapy ; Dysbiosis ; *Gastrointestinal Microbiome/drug effects ; Humans ; Intestinal Mucosa/*metabolism/*microbiology/pathology ; Metabolic Networks and Pathways/drug effects ; Molecular Targeted Therapy ; Protein Binding ; Receptors, Cytoplasmic and Nuclear/metabolism ; }, abstract = {The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids-microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids-microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.}, }
@article {pmid31289031, year = {2019}, author = {Pianko, MJ and Devlin, SM and Littmann, ER and Chansakul, A and Mastey, D and Salcedo, M and Fontana, E and Ling, L and Tavitian, E and Slingerland, JB and Slingerland, AE and Clurman, A and Gomes, ALC and Taur, Y and Pamer, EG and Peled, JU and van den Brink, MRM and Landgren, O and Lesokhin, AM}, title = {Minimal residual disease negativity in multiple myeloma is associated with intestinal microbiota composition.}, journal = {Blood advances}, volume = {3}, number = {13}, pages = {2040-2044}, pmid = {31289031}, issn = {2473-9537}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; K30 RR022277/RR/NCRR NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; L30 CA220724/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; UL1 TR000457/TR/NCATS NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Bone Marrow/pathology ; Combined Modality Therapy ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Multiple Myeloma/*diagnosis/*etiology/therapy ; Neoplasm Staging ; Neoplasm, Residual/*pathology ; Treatment Outcome ; }, abstract = {Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity after upfront treatment have superior outcomes compared with those who remain MRD[+] Recently, associations have been shown between specific commensal microbes and development of plasma cell disorders. Here, we report the association between intestinal microbiota composition and treatment outcome in MM. Microbiota composition of fecal samples collected from 34 MM patients after induction therapy and at the time of flow cytometry-based bone marrow MRD testing was determined by 16S ribosomal RNA sequencing. We observed a higher relative abundance of Eubacterium hallii in the 16 MRD[-] patients relative to the 18 MRD[+] patients. No association was observed between microbial relative abundance and autologous stem cell transplantation history or MM paraprotein isotype. No differences in microbiota α diversity were observed between MRD[-] and MRD[+] patients. The potential association of microbiota composition with treatment response in MM patients is an important parameter for additional correlative and clinical investigation.}, }
@article {pmid31288282, year = {2019}, author = {Enck, P and Mazurak, N}, title = {[Microbiota and irritable bowel syndrome: A critical inventory].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {57}, number = {7}, pages = {859-870}, doi = {10.1055/a-0901-2558}, pmid = {31288282}, issn = {1439-7803}, mesh = {Dysbiosis/complications/microbiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Irritable Bowel Syndrome/*therapy ; *Microbiota ; Probiotics/therapeutic use ; }, abstract = {This narrative review critically explores the role of the gut microbiota in functional bowel disorders of IBS-type. Starting with changes in the microbiota composition and diversity, as they have been often found in correlative IBS studies, it raises the question of cause and consequence, of sensitivity and specificity of findings in comparison to other diseases, and of the scientific and clinical options to manipulate the microbiota. This includes a discussion of pre- and probiotics and antibiotics as well as the role of nutrition and the microbiota exchange with fecal microbiota transfer (FMT). For IBS, most of these strategies have not been found to be successful therapies. This may be due to the heterogeneity of the disease itself, but eventually also due to the concepts of microbiological research, e. g., the term dysbiosis, or in methodological differences of the molecular-genetic research that are not visible in the published papers. Future studies should aim to identify those factors that may explain and predict the response to such therapies.}, }
@article {pmid31287532, year = {2019}, author = {Kamata, K and Watanabe, T and Minaga, K and Hara, A and Yoshikawa, T and Okamoto, A and Yamao, K and Takenaka, M and Park, AM and Kudo, M}, title = {Intestinal dysbiosis mediates experimental autoimmune pancreatitis via activation of plasmacytoid dendritic cells.}, journal = {International immunology}, volume = {31}, number = {12}, pages = {795-809}, doi = {10.1093/intimm/dxz050}, pmid = {31287532}, issn = {1460-2377}, mesh = {Administration, Oral ; Animals ; Autoimmune Pancreatitis/*immunology ; Bifidobacterium/isolation &amp; purification ; Dendritic Cells/*immunology ; Disease Models, Animal ; Dysbiosis/*immunology ; Female ; Intestines/*immunology ; Mice ; Mice, Inbred Strains ; }, abstract = {Autoimmune pancreatitis (AIP) is a pancreatic manifestation of a newly proposed disease entity, IgG4-related disease (IgG4-RD), characterized by enhanced IgG4 antibody responses and involvement of multiple organs. We have previously reported that innate immune activation contributes to the development of AIP and IgG4-RD, as these diseases are characterized by the production of IFN-α and IL-33 by plasmacytoid dendritic cells (pDCs) that mediate chronic fibroinflammatory responses. In this study, we investigated the roles played by innate immunity against intestinal microflora in experimental AIP induced in MRL/MpJ mice by repeated administrations of 100 µg of polyinosinic-polycytidylic acid [poly (I:C)]. Bowel sterilization with a broad spectrum of antibiotics inhibited pancreatic accumulation of pDCs producing IFN-α and IL-33, and thereby suppressed the development of AIP. Mice treated with 10 µg of poly (I:C) developed severe AIP equivalent to that induced by 100 µg of poly (I:C) upon co-housing with mice treated with 100 µg of poly (I:C). Fecal microbiota transplantation (FMT) from donor mice treated with 100 µg of poly (I:C) led to the development of severe AIP in the recipient mice upon injection with 10 µg of poly (I:C). Induction of severe AIP in mice with 10 µg of poly (I:C) was associated with pancreatic accumulation of pDCs producing IFN-α and IL-33 in the co-housing and FMT experiments. These data collectively suggest that innate immune responses against intestinal microflora are involved in the development of experimental AIP, and that intestinal dysbiosis increases sensitivity to experimental AIP via activation of pDCs.}, }
@article {pmid31281535, year = {2019}, author = {Shi, L and Sheng, J and Wang, M and Luo, H and Zhu, J and Zhang, B and Liu, Z and Yang, X}, title = {Combination Therapy of TGF-β Blockade and Commensal-derived Probiotics Provides Enhanced Antitumor Immune Response and Tumor Suppression.}, journal = {Theranostics}, volume = {9}, number = {14}, pages = {4115-4129}, pmid = {31281535}, issn = {1838-7640}, mesh = {Animals ; Animals, Genetically Modified ; Breast Neoplasms/therapy ; Cell Line, Tumor ; Female ; Flow Cytometry ; Gastrointestinal Microbiome/genetics/physiology ; Humans ; Immunotherapy/*methods ; Intestinal Mucosa/microbiology ; Liver Neoplasms/therapy ; Mice ; Probiotics/*therapeutic use ; RNA, Ribosomal, 16S/genetics ; Transforming Growth Factor beta/*metabolism ; Tumor Microenvironment/genetics/physiology ; }, abstract = {Galunisertib (Gal) is a transforming growth factor (TGF-β) blockade which is being investigated as a potential tumor immunotherapy candidate drug in clinical trials. However, primary or acquired resistance is often found in the recruited cancer patients, which limits its clinical application. Tumor immune microenvironment can be regulated by intestinal microbiota, leading to different therapeutic outcomes. It is hypothesized that manipulation of cancer patients' intestinal microbiome in the early stage of therapy may be a promising strategy to improve the therapeutic efficacy of Gal. Methods: 4T1 and H22 subcutaneous tumor bearing mice were used to evaluate the therapeutic effect. Escherichia coli strain Nissle 1917 (EcN), a widely used probiotic bacteria, was orally delivered to the tumor bearing mice daily along with Gal treatment. Antitumor effect of the combination therapy was evaluated by tumor volume, histological staining of tumor tissues. Furthermore, flow cytometry was performed to analyze the alteration of immune microenvironment in tumor bed after treatment. The suppressing effect of the combination therapy on tumor invasiveness and metastasis was evaluated in both mice and zebrafish xenografts models. Fecal sample 16S rRNA gene sequencing was conducted to analyze changes of intestinal microbial diversity. The effect of intestinal microbiota on tumor suppression after receiving EcN was further tested by fecal transplant. Results: The therapeutic outcomes in tumor growth inhibition and metastasis suppression of Gal were significantly potentiated by EcN, resulting from the strengthened antitumor immunity. EcN was able to relieve the immunosuppressive tumor microenvironment, which was evidenced by enhanced tumor-specific effector T cells infiltration and dendritic cells activation. Intestinal microbiota was modulated by EcN, illustrated by a shift of gut microbiome toward certain beneficial bacteria. Conclusion: These results suggested that Gal combined with EcN might be a novel therapeutic approach with great potential of clinical implications for cancer prevention or treatment.}, }
@article {pmid31274092, year = {2019}, author = {Henrot, C and Kuksin, M}, title = {[The intestinal virobiota, a new component in the interactions between the microbiota and the immune system].}, journal = {Medecine sciences : M/S}, volume = {35}, number = {6-7}, pages = {578-580}, doi = {10.1051/medsci/2019113}, pmid = {31274092}, issn = {1958-5381}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Colorectal Neoplasms/etiology/virology ; Enteritis/chemically induced/immunology/virology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*immunology ; Humans ; *Immune System ; Intestines/*virology ; Mice ; Norovirus/*immunology/pathogenicity ; Probiotics/administration &amp; dosage ; }, }
@article {pmid31273923, year = {2019}, author = {Durgan, DJ}, title = {Evidence for a gut-immune-vascular axis in the development of hypertension.}, journal = {Acta physiologica (Oxford, England)}, volume = {227}, number = {1}, pages = {e13338}, doi = {10.1111/apha.13338}, pmid = {31273923}, issn = {1748-1716}, mesh = {Animals ; Blood Pressure ; *Fecal Microbiota Transplantation ; *Hypertension ; Immune System ; Rats ; }, }
@article {pmid31273774, year = {2019}, author = {Kirby, TO and Brown, M and Ochoa-Repáraz, J and Roullet, JB and Gibson, KM}, title = {Microbiota Manipulation as a Metagenomic Therapeutic Approach for Rare Inherited Metabolic Disorders.}, journal = {Clinical pharmacology and therapeutics}, volume = {106}, number = {3}, pages = {505-507}, pmid = {31273774}, issn = {1532-6535}, support = {R01 EY027476/EY/NEI NIH HHS/United States ; }, mesh = {4-Aminobutyrate Transaminase/deficiency ; Amino Acid Metabolism, Inborn Errors/physiopathology/therapy ; Animals ; Developmental Disabilities/physiopathology/therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Metabolism, Inborn Errors/*physiopathology/therapy ; Mice ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; RNA, Ribosomal, 16S/metabolism ; Rare Diseases/*physiopathology/therapy ; Severity of Illness Index ; Succinate-Semialdehyde Dehydrogenase/deficiency ; }, }
@article {pmid31273647, year = {2019}, author = {Rode, AA and Bytzer, P and Pedersen, OB and Engberg, J}, title = {Establishing a donor stool bank for faecal microbiota transplantation: methods and feasibility.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {38}, number = {10}, pages = {1837-1847}, pmid = {31273647}, issn = {1435-4373}, mesh = {Adolescent ; Adult ; Biological Specimen Banks/*organization &amp; administration ; Fecal Microbiota Transplantation/*methods ; Female ; Helicobacter Infections/*therapy ; Humans ; Male ; Middle Aged ; *Tissue Donors ; Young Adult ; }, abstract = {Faecal microbiota transplantation (FMT) is a promising treatment, but donor selection and implementation in clinical practice are difficult. Here, we describe the establishment of a donor stool bank based on the Tissue Act. Stool donors were recruited among blood donors and asked to donate five times in a month. A screening questionnaire, a medical interview and testing of blood and stool were conducted before and after donations. Donations were made at home and transported to the lab, where 50 g of stool was suspended and filtered in saline and 20-mL glycerol (final concentration of 10%) to a volume of 170 mL. The processed stool was assigned a batch number, frozen within 2 h after defecation and stored at - 80 °C for up to 1 year. All steps were documented and cross-checked before donor stool were released for clinical use. Thirteen donors were eligible at the first interview and started donations. Two donors were excluded due to a positive Helicobacter pylori test, two withdrew consent and one was lost to follow-up. One donor took a single dose of NSAIDs 2 days prior to a donation, which was discarded. There were no other excluding findings at the second interview or testing. Eight of the 13 donors were approved as stool donors. All donated five times with each donation yielding 1-6 portions. Eighty-four portions were released for clinical use. Recruiting stool donors among blood donors is safe and effective. The Tissue Act yields an appropriate regulative framework for FMT.}, }
@article {pmid31272391, year = {2019}, author = {Tian, Y and Zhou, Y and Huang, S and Li, J and Zhao, K and Li, X and Wen, X and Li, XA}, title = {Fecal microbiota transplantation for ulcerative colitis: a prospective clinical study.}, journal = {BMC gastroenterology}, volume = {19}, number = {1}, pages = {116}, pmid = {31272391}, issn = {1471-230X}, support = {2016JY0090//Natural Science Foundation of Science and Technology Department of Sichuan Province/ ; 17ZD012//Science and Technology Project of The Health Planning Committee of Sichuan/ ; 16ZA0280//Natural Science Foundation of Education Department of Sichuan Province/ ; 16TD0028//Innovative Group Foundation of Education Department of Sichuan Province/ ; S16019//Foundation of the Medical Association of Sichuan Province/ ; ZYFY2017XH04//Foundation of the First Affiliated Hospital of Chengdu Medical College/ ; }, mesh = {Aged ; Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Prospective Studies ; Remission Induction/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation may contribute to disease remission in ulcerative colitis; however, the factors that determine the effects of treatment remain unknown. The aim of the present study was to prospectively investigate the clinical efficacy of fecal microbiota transplantation in patients with ulcerative colitis and identify the bacterial signatures associated with clinical remission.<br><br>METHODS: A total of 20 patients with ulcerative colitis were included in this prospective and uncontrolled study. All patients underwent gastroscopy five times, once every 3&#x2009;weeks. Clinical indices were used to assess the efficacy of fecal microbiota transplantation, as well as the Mayo score, a score used to evaluate the extent of intestinal mucosal lesions in patients with ulcerative colitis. The changes in intestinal flora were detected by 16S ribosomal RNA-sequencing, and the relationship between ulcerative colitis and intestinal flora was analyzed.<br><br>RESULTS: After treatment, clinical index scores for diarrhea, abdominal pain, and blood stool decreased significantly (p&#x2009;<&#x2009;0.05). Erythrocyte sedimentation rate and C-reactive protein levels had not changed significantly; however, the clinical index score for intestinal mucosal lesions and the Mayo score decreased significantly. In addition, 16S ribosomal RNA-sequencing revealed that the intestinal flora in patients diagnosed with ulcerative colitis was different from that of donors.<br><br>CONCLUSION: Fecal microbiota transplantation has a potential therapeutic value for the treatment of ulcerative colitis as it changes the abundance of bacterial flora and improves the scores for diarrhea, abdominal pain, and mucous membrane lesions in patients with this disease.<br><br>TRIAL REGISTRATION: The clinical trial was retrospectively registered with ClinicalTrials.gov (NCT03016780) on January 11th, 2017.}, }
@article {pmid31269444, year = {2019}, author = {Bradley, KC and Finsterbusch, K and Schnepf, D and Crotta, S and Llorian, M and Davidson, S and Fuchs, SY and Staeheli, P and Wack, A}, title = {Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection.}, journal = {Cell reports}, volume = {28}, number = {1}, pages = {245-256.e4}, doi = {10.1016/j.celrep.2019.05.105}, pmid = {31269444}, issn = {2211-1247}, support = {FC001206/CRUK_/Cancer Research UK/United Kingdom ; FC001206//Wellcome Trust/United Kingdom ; MC_U117597139/MRC_/Medical Research Council/United Kingdom ; FC001206/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bone Marrow Cells/cytology/metabolism ; Cell Line ; Chimera/immunology ; Epithelial Cells/immunology/metabolism ; Fecal Microbiota Transplantation ; Gene Expression Regulation, Viral/immunology ; Hematopoietic Stem Cells/immunology/metabolism/virology ; Humans ; *Influenza A virus/growth &amp; development/immunology ; Influenza, Human/drug therapy/*immunology/*microbiology/pathology ; Interferon Type I/metabolism ; Leukocyte Common Antigens/genetics/immunology ; Lung/drug effects/*immunology/microbiology/virology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microbiota/*immunology ; RNA-Seq ; Receptor, Interferon alpha-beta/genetics/*metabolism ; Stromal Cells/immunology/metabolism/microbiology/virology ; }, abstract = {Type I interferon (IFNα/β) pathways are fine-tuned to elicit antiviral protection while minimizing immunopathology; however, the initiating stimuli, target tissues, and underlying mechanisms are unclear. Using models of physiological and dysregulated IFNα/β receptor (IFNAR1) surface expression, we show here that IFNAR1-dependent signals set the steady-state IFN signature in both hematopoietic and stromal cells. Increased IFNAR1 levels promote a lung environment refractory to early influenza virus replication by elevating the baseline interferon signature. Commensal microbiota drive the IFN signature specifically in lung stroma, as shown by antibiotic treatment and fecal transplantation. Bone marrow chimera experiments identify lung stromal cells as crucially important for early antiviral immunity and stroma-immune cell interaction for late antiviral resistance. We propose that the microbiota-driven interferon signature in lung epithelia impedes early virus replication and that IFNAR1 surface levels fine-tune this signature. Our findings highlight the interplay between bacterial and viral exposure, with important implications for antibiotic use.}, }
@article {pmid31266629, year = {2019}, author = {Martel, B and Saint-Lorant, G}, title = {[Pharmaceutical system of fecal microbiota transplantation: Heterogeneous practices].}, journal = {Annales pharmaceutiques francaises}, volume = {77}, number = {5}, pages = {435-442}, doi = {10.1016/j.pharma.2019.06.001}, pmid = {31266629}, issn = {0003-4509}, mesh = {Clostridium Infections/microbiology/therapy ; Enterocolitis, Pseudomembranous/microbiology/therapy ; Fecal Microbiota Transplantation/economics/*methods ; Feces/*microbiology ; France ; Health Care Surveys ; Humans ; Microbiota ; Pharmacy Service, Hospital/economics/*organization &amp; administration ; Specimen Handling ; }, abstract = {OBJECTIVE: To describe current pharmaceutical practice in French hospitals regarding fecal microbiota transplantation in terms of prescription, preparation and compounding, as well as local legislation.<br><br>MATERIAL AND METHODS: A national survey was conducted at 28 French university hospital centers followed by the sending of a GoogleForm[&#xae;] questionnaire from June to August 2018 in the 16 respondent centers either performing or subcontracting fecal microbiota transplant.<br><br>RESULTS: All hospitals performing or subcontracting fecal transplant (n=16,%57) report prescription indication of recurrent Clostridium difficile infection treatment, and 6 of them also as part of a clinical trial protocol. In hospitals performing fecal transplant themselves (n=11), the number of pre-donation consultations with donors varies from one (n=6) to two (n=5). Fecal sample is collected at the donor's home in 45% of cases. Route of administration for transplant is either naso-gastric administration (n=4), rectal (n=4) or both (n=5). Fecal samples for transplant are compounded either in the hospital pharmacy (n=73%) or in the laboratory (27%). Thawing methods include refrigeration between 2-8&#xb0;C (50%), room temperature (25%) and water bath (25%). Billing system and reporting to health authorities are highly heterogeneous from one hospital to another.<br><br>CONCLUSION: This survey shows significant pharmaceutical practice heterogeneity within French hospitals regarding fecal microbiota transplantation despite the existence of national and European recommendations.}, }
@article {pmid31262981, year = {2019}, author = {Morjaria, S and Schluter, J and Taylor, BP and Littmann, ER and Carter, RA and Fontana, E and Peled, JU and van den Brink, MRM and Xavier, JB and Taur, Y}, title = {Antibiotic-Induced Shifts in Fecal Microbiota Density and Composition during Hematopoietic Stem Cell Transplantation.}, journal = {Infection and immunity}, volume = {87}, number = {9}, pages = {}, pmid = {31262981}, issn = {1098-5522}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Anti-Bacterial Agents/*pharmacology ; Bacteria/genetics ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Male ; Microbiota/*drug effects ; Middle Aged ; RNA, Ribosomal, 16S ; }, abstract = {Dramatic microbiota changes and loss of commensal anaerobic bacteria are associated with adverse outcomes in hematopoietic cell transplantation (HCT) recipients. In this study, we demonstrate these dynamic changes at high resolution through daily stool sampling and assess the impact of individual antibiotics on those changes. We collected 272 longitudinal stool samples (with mostly daily frequency) from 18 patients undergoing HCT and determined their composition by multiparallel 16S rRNA gene sequencing as well as the density of bacteria in stool by quantitative PCR (qPCR). We calculated microbiota volatility to quantify rapid shifts and developed a new dynamic systems inference method to assess the specific impact of antibiotics. The greatest shifts in microbiota composition occurred between stem cell infusion and reconstitution of healthy immune cells. Piperacillin-tazobactam caused the most severe declines among obligate anaerobes. Our approach of daily sampling, bacterial density determination, and dynamic systems modeling allowed us to infer the independent effects of specific antibiotics on the microbiota of HCT patients.}, }
@article {pmid31261545, year = {2019}, author = {Huang, H and Xu, H and Luo, Q and He, J and Li, M and Chen, H and Tang, W and Nie, Y and Zhou, Y}, title = {Fecal microbiota transplantation to treat Parkinson's disease with constipation: A case report.}, journal = {Medicine}, volume = {98}, number = {26}, pages = {e16163}, pmid = {31261545}, issn = {1536-5964}, mesh = {Aged ; Constipation/*complications/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Male ; Parkinson Disease/*complications/*therapy ; }, abstract = {RATIONALE: Fecal microbiota transplantation (FMT) is recognized as an emerging treatment through reconstruction of gut microbiota. Parkinson's disease is a neurodegenerative disorder, which is accompanied by constipation. Here we first reported a patient with Parkinson's disease and constipation that were obviously relieved after FMT.<br><br>PATIENT CONCERNS: A 71-year-old male patient presented with 7 years of resting tremor, bradykinesia (first inflicted the upper limbs and subsequently spread to lower limbs), and intractable constipation (defecation needing more than 30 minutes).<br><br>DIAGNOSES: Parkinson's disease for 7 years; constipation >3 years.<br><br>INTERVENTIONS: The patient had used madopar, pramipexole, and amantadine for anti-Parkinson and showed partially mitigation while laxative therapy for constipation failed. Finally FMT was performed.<br><br>OUTCOMES: The patient successfully defecated within 5 minutes and maintained daily unobstructed defecation until the end of follow-up. The patient's tremor in legs almost disappeared at 1 week after FMT but recurred in the right lower extremity at 2 months after FMT.<br><br>LESSONS: Gut microbiota reconstruction may have therapeutic effects for Parkinson's disease patients, especially those who have gastrointestinal symptoms and limited treatment choices.}, }
@article {pmid31258528, year = {2019}, author = {Leshem, A and Horesh, N and Elinav, E}, title = {Fecal Microbial Transplantation and Its Potential Application in Cardiometabolic Syndrome.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {1341}, pmid = {31258528}, issn = {1664-3224}, support = {/ERC_/European Research Council/International ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cardiovascular Diseases/*therapy ; Dysbiosis/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/*therapy ; Metabolic Diseases/*therapy ; Obesity/*therapy ; Syndrome ; }, abstract = {Newly revealed links between inflammation, obesity, and cardiometabolic syndrome have created opportunities to try previously unexplored therapeutic modalities in these common and life-risking disorders. One potential modulator of these complex disorders is the gut microbiome, which was described in recent years to be altered in patients suffering from features of cardiometabolic syndrome and to transmit cardiometabolic phenotypes upon transfer into germ-free mice. As a result, there is great interest in developing new modalities targeting the altered commensal bacteria as a means of treatment for cardiometabolic syndrome. Fecal microbiota transplantation (FMT) is one such modality in which a disease-associated microbiome is replaced by a healthy microbiome configuration. So far clinical use of FMT has been overwhelmingly successful in recurrent Clostridium difficile infection and is being extensively studied in other microbiome-associated pathologies such as cardiometabolic syndrome. This review will focus on the rationale, promises and challenges in FMT utilization in human disease. In particular, it will overview the role of the gut microbiota in cardiometabolic syndrome and the rationale, experience, and prospects of utilizing FMT treatment as a potential preventive and curative treatment of metabolic human disease.}, }
@article {pmid31258315, year = {2019}, author = {Otrompke, J}, title = {Digestive Disease Week 2019.}, journal = {P &amp; T : a peer-reviewed journal for formulary management}, volume = {44}, number = {7}, pages = {428-429}, pmid = {31258315}, issn = {1052-1372}, abstract = {We review selected sessions on the questionable benefits of fecal microbiota transplant; intrahepatic cholestasis of pregnancy; weight-loss drugs in combination with intragastric balloon endoscopy; and beta blockers in pancreatic cancer.}, }
@article {pmid31254675, year = {2020}, author = {Kelly, CR and Fischer, M and Grinspan, A and Allegretti, JR}, title = {Patients Eligible for Trials of Microbe-Based Therapeutics Do Not Represent the Population With Recurrent Clostridioides difficile Infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {18}, number = {5}, pages = {1099-1101}, doi = {10.1016/j.cgh.2019.06.034}, pmid = {31254675}, issn = {1542-7714}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Patient Participation ; Randomized Controlled Trials as Topic ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Although there are many industry-funded trials of microbe-based therapeutics for Clostridioides (formerly Clostridium) difficile infection (CDI), not all patients are eligible for these trials, due to their strict enrollment criteria. Furthermore, given the widespread availability of fecal microbiota transplantation (FMT) and overwhelming evidence to support its efficacy, patients might refuse enrollment in trials with a placebo group. We analyzed willingness and eligibility of patients with recurrent CDI to participate in randomized controlled trials of microbe-based therapeutic agents.<br><br>METHODS: We performed a retrospective study of 199 patients referred to 4 tertiary referral centers for treatment of CDI from August 1, 2018 through January 31, 2019. We collected data on eligibility for FMT and enrollment in randomized controlled trials.<br><br>RESULTS: Of 130 patients deemed appropriate for FMT, 98 patients (75%) were ineligible for participation in a randomized controlled trial and 16 patients (17%) were eligible but refused to enroll. Immune compromise and inflammatory bowel diseases were the most common reasons for exclusion from trials.<br><br>CONCLUSIONS: Most patients with CDI who meet the guideline criteria for FMT are ineligible or unwilling to participate in randomized controlled trials of microbe-based therapeutics. Trial populations therefore do not represent the population of patients with CDI.}, }
@article {pmid31250122, year = {2019}, author = {Aron-Wisnewsky, J and Clément, K and Nieuwdorp, M}, title = {Fecal Microbiota Transplantation: a Future Therapeutic Option for Obesity/Diabetes?.}, journal = {Current diabetes reports}, volume = {19}, number = {8}, pages = {51}, pmid = {31250122}, issn = {1539-0829}, mesh = {Animals ; *Clostridium Infections ; *Diabetes Mellitus ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Obesity ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: The aim of this review is to summarize the current data available on the metabolic effects of fecal microbiota transplantation (FMT) including obesity and glucose metabolism in humans.<br><br>RECENT FINDINGS: Gut microbiota dysbiosis is a frequent characteristic observed in obesity and related metabolic diseases. Pieces of evidence mostly generated in mouse models suggest that rescuing this dysbiosis associates with improved metabolism. In humans, dietary or bariatric surgery interventions are often accompanied by complete or partial restoration of this dysbiosis together with weight reduction and metabolic amelioration. FMT is an interesting option to modify gut microbiota and has been associated with improved clinical outcomes, albeit only used in routine care for Clostridium difficile infection. However, there are only limited data on using FMT in the metabolic context. FMT from lean donors significantly improves insulin sensitivity in obese subjects with metabolic syndrome. However, there is a wide range of clinical responses. Interestingly in subjects with high microbial gene richness at baseline and when FMT donors that are metabolically compromised are used, no metabolic improvement is seen. Moreover, more studies evaluating the effect of FMT in patients with overt type 2 diabetes are warranted. Furthermore, interventions (in the receiver prior to FMT) aiming to enhance FMT response also need evaluation.}, }
@article {pmid31250035, year = {2019}, author = {Wang, G and Huang, S and Wang, Y and Cai, S and Yu, H and Liu, H and Zeng, X and Zhang, G and Qiao, S}, title = {Bridging intestinal immunity and gut microbiota by metabolites.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {76}, number = {20}, pages = {3917-3937}, pmid = {31250035}, issn = {1420-9071}, support = {31420103908//National Natural Science Foundation of China/ ; 2017YFD0500506//Key Technologies Research and Development Program/ ; }, mesh = {*Adaptive Immunity ; Amino Acids/immunology/metabolism ; Animals ; Bile Acids and Salts/immunology/metabolism ; Dysbiosis/immunology/*metabolism/microbiology/therapy ; Fatty Acids/immunology/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Germ-Free Life/immunology ; Homeostasis/immunology ; Humans ; *Immunity, Innate ; Intestinal Mucosa/immunology/*metabolism/microbiology ; Lymphocytes/immunology/metabolism/microbiology ; Metabolome/*immunology ; Myeloid Cells/immunology/metabolism/microbiology ; Symbiosis/immunology ; }, abstract = {The gastrointestinal tract is the site of nutrient digestion and absorption and is also colonized by diverse, highly mutualistic microbes. The intestinal microbiota has diverse effects on the development and function of the gut-specific immune system, and provides some protection from infectious pathogens. However, interactions between intestinal immunity and microorganisms are very complex, and recent studies have revealed that this intimate crosstalk may depend on the production and sensing abilities of multiple bioactive small molecule metabolites originating from direct produced by the gut microbiota or by the metabolism of dietary components. Here, we review the interplay between the host immune system and the microbiota, how commensal bacteria regulate the production of metabolites, and how these microbiota-derived products influence the function of several major innate and adaptive immune cells involved in modulating host immune homeostasis.}, }
@article {pmid31247468, year = {2019}, author = {Ma, Q and Li, Y and Li, P and Wang, M and Wang, J and Tang, Z and Wang, T and Luo, L and Wang, C and Wang, T and Zhao, B}, title = {Research progress in the relationship between type 2 diabetes mellitus and intestinal flora.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {117}, number = {}, pages = {109138}, doi = {10.1016/j.biopha.2019.109138}, pmid = {31247468}, issn = {1950-6007}, mesh = {*Biomedical Research ; Diabetes Mellitus, Type 2/*microbiology/prevention &amp; control/therapy ; Fatty Acids/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Models, Biological ; }, abstract = {Type 2 diabetes mellitus (T2DM) is a common clinical chronic disease, while its pathogenesis is still inconclusive. Intestinal flora, the largest micro-ecological system in the human body, is involved in, meanwhile has a major impact on the body's material and energy metabolism. Recent studies have shown that in addition to obesity, genetics, and islet dysfunction, the disturbance of intestinal flora may partly give rise to diabetes. In this paper, we summarized the current research on the correlation between T2DM and intestinal flora, and concluded the pathological mechanisms of intestinal flora involved in T2DM. Moreover, the ideas and methods of prevention and treatment of T2DM based on intestinal flora were proposed, providing theoretical basis and literature reference for the treatment of T2DM and its complications based on the regulation of intestinal flora.}, }
@article {pmid31245969, year = {2019}, author = {Taylor, VH}, title = {The microbiome and mental health: Hope or hype?.}, journal = {Journal of psychiatry &amp; neuroscience : JPN}, volume = {44}, number = {4}, pages = {219-222}, pmid = {31245969}, issn = {1488-2434}, mesh = {Dysbiosis/*complications/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mental Disorders/*etiology/therapy ; *Probiotics/therapeutic use ; }, }
@article {pmid31244784, year = {2019}, author = {Chong, PP and Chin, VK and Looi, CY and Wong, WF and Madhavan, P and Yong, VC}, title = {The Microbiome and Irritable Bowel Syndrome - A Review on the Pathophysiology, Current Research and Future Therapy.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1136}, pmid = {31244784}, issn = {1664-302X}, abstract = {Irritable bowel syndrome (IBS) is a functional disorder which affects a large proportion of the population globally. The precise etiology of IBS is still unknown, although consensus understanding proposes IBS to be of multifactorial origin with yet undefined subtypes. Genetic and epigenetic factors, stress-related nervous and endocrine systems, immune dysregulation and the brain-gut axis seem to be contributing factors that predispose individuals to IBS. In addition to food hypersensitivity, toxins and adverse life events, chronic infections and dysbiotic gut microbiota have been suggested to trigger IBS symptoms in tandem with the predisposing factors. This review will summarize the pathophysiology of IBS and the role of gut microbiota in relation to IBS. Current methodologies for microbiome studies in IBS such as genome sequencing, metagenomics, culturomics and animal models will be discussed. The myriad of therapy options such as immunoglobulins (immune-based therapy), probiotics and prebiotics, dietary modifications including FODMAP restriction diet and gluten-free diet, as well as fecal transplantation will be reviewed. Finally this review will highlight future directions in IBS therapy research, including identification of new molecular targets, application of 3-D gut model, gut-on-a-chip and personalized therapy.}, }
@article {pmid31242213, year = {2019}, author = {Saito, Y and Hinoi, T and Adachi, T and Miguchi, M and Niitsu, H and Kochi, M and Sada, H and Sotomaru, Y and Sakamoto, N and Sentani, K and Oue, N and Yasui, W and Tashiro, H and Ohdan, H}, title = {Synbiotics suppress colitis-induced tumorigenesis in a colon-specific cancer mouse model.}, journal = {PloS one}, volume = {14}, number = {6}, pages = {e0216393}, pmid = {31242213}, issn = {1932-6203}, mesh = {Animals ; Carcinogenesis/*drug effects ; Colitis/*complications ; Colonic Neoplasms/*etiology/metabolism/microbiology/*pathology ; Cytoplasm/drug effects/metabolism ; Disease Models, Animal ; Feces/microbiology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Heterozygote ; Interleukin-6/genetics ; Intestinal Mucosa/drug effects/metabolism/pathology ; Mice ; Microbiota/drug effects ; Prebiotics ; Probiotics/pharmacology ; STAT3 Transcription Factor/genetics ; *Synbiotics ; Tumor Necrosis Factor-alpha/genetics ; beta Catenin/metabolism ; }, abstract = {Although synbiotics may be effective in maintaining remission of inflammatory bowel disease, their anticarcinogenic effects are still debated. To address this issue, we evaluated the effects of synbiotics, probiotics, and prebiotics on tumorigenesis using a CDX2P-Cre; Apc+/flox mouse model harboring a colon-specific Apc knock out, which develops adenoma and adenocarcinoma of the colon. Dextran sodium sulfate (DSS)-administration promoted colonic tumor development in CDX2P-Cre; Apc+/flox mice, and these tumors were associated with loss of Apc heterozygosity, as confirmed by observation of well-differentiated adenocarcinomas with β-catenin accumulation in tumor cell cytoplasm. Synbiotics-treatment suppressed dextran sodium sulfate-induced colitis in CDX2P-Cre; Apc+/flox mice, thereby reducing mortality, and inhibited tumorigenesis accelerated by DSS-administration. Conversely, neither probiotics nor prebiotics had any effect on inflammation and tumorigenesis. Lactobacillus casei and Bifidobacterium breve were detected in the fecal microbiota of probiotics-treated mice. Synbiotics-treatment suppressed DSS-induced expression of IL-6, STAT-3, COX-2, and TNF-α gene transcripts in normal colonic epithelium, indicating the possibility of suppressing tumor development. Importantly, these genes may be potential therapeutic targets in inflammation-associated colon cancer.}, }
@article {pmid31241182, year = {2019}, author = {Jørgensen, SMD and Hvas, CL and Dahlerup, JF and Mikkelsen, S and Ehlers, L and Hammeken, LH and Licht, TR and Bahl, MI and Erikstrup, C}, title = {Banking feces: a new frontier for public blood banks?.}, journal = {Transfusion}, volume = {59}, number = {9}, pages = {2776-2782}, pmid = {31241182}, issn = {1537-2995}, mesh = {Blood Banks/legislation &amp; jurisprudence/*organization &amp; administration/*trends ; Blood Donors ; Donor Selection/methods/standards/trends ; *Fecal Microbiota Transplantation/methods/standards/statistics &amp; numerical data/trends ; *Feces ; Health Services Needs and Demand ; Humans ; Legislation, Medical/standards ; Practice Guidelines as Topic/standards ; Public Sector ; Risk Assessment ; Blood Banking/methods ; }, abstract = {Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection and is potentially beneficial in other microbiota-related disorders. The provision of FMT in routine clinical practice requires an extensive infrastructure that is reliant on voluntary donors. Alongside an increasing demand for FMT, the logistic barriers of a large-scale donor-dependent operation and the difficulties among health authorities to regulate FMT limit the dissemination of sustainable FMT services. Blood centers are large organizations that handle a multitude of donor-dependent operations on a daily basis. Blood and feces share many of the same dependencies, and feces may present a new opportunity for the blood services to handle. In this paper, we describe how an FMT service may be established and embedded within the blood service infrastructure, and we explain the benefits of using blood donors as feces donors. We further explore the current indications of FMT, the challenges related to the lack of legislation, and the future perspectives for blood banks to meet a new and increasing demand.}, }
@article {pmid31240781, year = {2019}, author = {Kelgeri, C and Valamparampil, J and Shanmugam, N and Srinivas Reddy, M and Swaminathan, S and Rela, M}, title = {An unusual cause of graft loss in pediatric liver transplant recipient-Fasciola hepatica.}, journal = {Pediatric transplantation}, volume = {23}, number = {6}, pages = {e13521}, doi = {10.1111/petr.13521}, pmid = {31240781}, issn = {1399-3046}, mesh = {Animals ; Child ; Cholangitis/drug therapy ; Contrast Media ; End Stage Liver Disease/diagnostic imaging/*surgery ; Fasciola hepatica ; Fascioliasis/*complications ; Female ; Graft Rejection/*parasitology ; Humans ; Immunosuppression Therapy ; Immunosuppressive Agents/therapeutic use ; India ; *Liver Transplantation ; Morocco ; Mycophenolic Acid/therapeutic use ; Stem Cell Transplantation ; Tacrolimus/therapeutic use ; Tomography, X-Ray Computed ; }, abstract = {Fascioliasis is caused by the trematode liver fluke Fasciola hepatica. Humans are accidental hosts getting infected after ingesting contaminated plants or water. 90 million people in 75 nations are at risk of infection with F hepatica. Immunosuppressed patients are higher risk of acquiring infection and may present with atypical manifestations. Patients can present with hepatic involvement, biliary features or a combination of both. Confirmation of the diagnosis is by demonstration of live parasites or eggs in bile or feces, serology (immunoelectrophoresis, indirect immunofluorescence, indirect hemagglutination), ELISA, typical imaging findings or a combination of any of the above. The drug of choice for treatment is triclabendazole. Fascioliasis should always be considered as a possibility in post-LT patients with findings of hepatobiliary disorder from endemic areas. Unfamiliarity with this infection in non-endemic areas often eludes prompt diagnosis thereby increasing the morbidity. We report the first case of fascioliasis in a pediatric liver transplant recipient leading to graft loss and mortality.}, }
@article {pmid31239866, year = {2019}, author = {Xu, Z and Liu, T and Zhou, Q and Chen, J and Yuan, J and Yang, Z}, title = {Roles of Chinese Medicine and Gut Microbiota in Chronic Constipation.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2019}, number = {}, pages = {9372563}, pmid = {31239866}, issn = {1741-427X}, abstract = {Chronic constipation is a common gastrointestinal dysfunction, but its aetiology and pathogenesis are still unclear. Interestingly, the compositions of the gut microbiota in constipation patients and healthy controls are different. Various studies reported the different gut microbiota alterations in constipation patients, but most studies indicated that constipation patients showed the decreased beneficial bacteria and the reduced species richness of gut bacteria. Besides, the alterations in the gut microbiota may lead to constipation and constipation-related symptoms and the regulation of gut microbiota has a positive effect on gut functional diseases such as constipation. Microbial treatment methods, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, can be used to regulate gut microbiota. Increasing evidences have suggested that Chinese medicine (CM) has a good therapeutic effect on chronic constipation. Chinese medicine is well known for its multitarget and multimode effects on diseases as well as less side effects. In previous studies, after the treatment of constipation with CM, the gut microbiota was restored, indicating that the gut microbiota might be the target or important way for CM to exert its efficacy. In this review, we summarized the effects of microbial treatment and CM on the gut microbiota of constipation patients and discussed the relationship between CM and gut microbiota.}, }
@article {pmid31238507, year = {2019}, author = {El-Salhy, M and Hausken, T and Hatlebakk, JG}, title = {Increasing the Dose and/or Repeating Faecal Microbiota Transplantation (FMT) Increases the Response in Patients with Irritable Bowel Syndrome (IBS).}, journal = {Nutrients}, volume = {11}, number = {6}, pages = {}, pmid = {31238507}, issn = {2072-6643}, support = {40415//Helse Fonna/ ; 912234//Helse Vest/ ; }, mesh = {Adult ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/diagnosis/microbiology/*therapy ; Male ; Quality of Life ; Retreatment ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiome transplantation (FMT) appears to be an effective method for treating irritable bowel syndrome (IBS) patients. However, it is not clear if a high transplant dose and/or repeating FMT are/is needed to ensure a response. The present study was undertaken to clarify this matter.<br><br>METHODS: Ten IBS patients who did not respond to a 30-g transplant subsequently received a 60-g transplant into the duodenum via a gastroscope. The patients provided faecal samples before and 1 month after FMT. They completed five questionnaires measuring symptoms, fatigue and quality of life at baseline and then at 2 weeks, 1 month and 3 months after FMT. The dysbiosis index (DI) was measured using the GA-map Dysbiosis Test[&#xae;].<br><br>RESULTS: Seven patients (70%) responded to the 60-g transplant, with significant clinical improvements in the abdominal symptoms, fatigue and quality of life in 57%, 80% and 67% of these patients. The 60-g transplant also reduced the DI.<br><br>CONCLUSION: FMT is an effective treatment for IBS. A high-dose transplant and/or repeated FMT increase the response rate and the intensity of the effects of FMT.}, }
@article {pmid31238017, year = {2019}, author = {Wang, Y and Zhao, W and Shi, J and Wang, J and Hao, J and Pang, X and Huang, X and Chen, X and Li, Y and Jin, R and Ge, Q}, title = {Intestinal microbiota contributes to altered glucose metabolism in simulated microgravity mouse model.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {9}, pages = {10140-10151}, doi = {10.1096/fj.201900238RR}, pmid = {31238017}, issn = {1530-6860}, mesh = {Acute-Phase Proteins ; Akkermansia ; Animals ; Bifidobacterium/isolation &amp; purification ; Carrier Proteins/blood ; Corticosterone/blood ; Dysbiosis/*metabolism ; Endotoxemia/prevention &amp; control ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Glucose/*metabolism ; Glucose Intolerance/*etiology ; Head-Down Tilt ; Hepatitis/prevention &amp; control ; Housing, Animal ; Insulin Resistance ; Liver/metabolism ; Male ; Membrane Glycoproteins/blood ; Mice ; Mice, Inbred C57BL ; Norepinephrine/blood ; Probiotics ; Random Allocation ; Specific Pathogen-Free Organisms ; Verrucomicrobia/isolation &amp; purification ; *Weightlessness/adverse effects ; }, abstract = {Exposure to space environment induces alterations in glucose and lipid metabolism that contribute to muscular atrophy, bone loss, and cardiovascular disorders. Intestinal microbiota is also changed, but its impact on spaceflight-related metabolic disorder is not clear. We investigated the relationship between glucose metabolic changes and gut dysbiosis in a hind limb-unloading (HU) mouse model, a well-accepted ground-based spaceflight analog. Impaired body weight gain, glucose intolerance, and peripheral insulin resistance were found in 2-4-wk HU mice. Reduced abundance of gut Bifidobacterium spp. and Akkermansia muciniphila was observed within 3 d of HU. The ground-based control (Ctrl) mice that were cohoused with HU mice showed similar patterns of dysbiosis and metabolic changes. Compared with the Ctrls, higher levels of plasma LPS-binding protein and altered transcription of Tnfa and glucose metabolism-related genes in the liver were observed in HU mice. The supplementation of Bifidobacterium spp. suppressed endotoxemia and liver inflammation and improved glucose tolerance in HU mice. The results indicate a close relationship between dysbiosis and altered glucose metabolism in the HU model and also emphasize the importance of evaluating intestinal microbiota in astronauts and its effect on glucose metabolism.-Wang, Y., Zhao, W., Shi, J., Wang, J., Hao, J., Pang, X., Huang, X., Chen, X., Li, Y., Jin, R., Ge, Q. Intestinal microbiota contributes to altered glucose metabolism in simulated microgravity mouse model.}, }
@article {pmid31236163, year = {2019}, author = {Singh, T and Bedi, P and Bumrah, K and Singh, J and Rai, M and Seelam, S}, title = {Updates in Treatment of Recurrent Clostridium difficile Infection.}, journal = {Journal of clinical medicine research}, volume = {11}, number = {7}, pages = {465-471}, pmid = {31236163}, issn = {1918-3003}, abstract = {Recurrent Clostridium difficile infection (CDI) is a perpetual problem that leads to increased economic burden, higher healthcare cost, and significant morbidity and mortality. Its treatment remains a challenge. While various treatment approaches have been attempted with different levels of success, robust data establishing the superiority of one approach over the others is lacking. In this article, we review the current evidence pertaining to conventional pharmacological treatment as well as fecal microbiota transplantation (FMT) as a novel, rapidly emerging treatment modality for recurrent CDI.}, }
@article {pmid31234928, year = {2019}, author = {Paetzold, B and Willis, JR and Pereira de Lima, J and Knödlseder, N and Brüggemann, H and Quist, SR and Gabaldón, T and Güell, M}, title = {Skin microbiome modulation induced by probiotic solutions.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {95}, pmid = {31234928}, issn = {2049-2618}, mesh = {Adult ; Bacteria/classification/isolation &amp; purification ; Bacterial Load ; Female ; Healthy Volunteers ; Humans ; Male ; *Microbiota ; Probiotics/*administration &amp; dosage/therapeutic use ; Propionibacteriaceae ; Skin/*microbiology ; Skin Diseases/therapy ; Young Adult ; }, abstract = {BACKGROUND: The skin is colonized by a large number of microorganisms, most of which are beneficial or harmless. However, disease states of skin have specific microbiome compositions that are different from those of healthy skin. Gut microbiome modulation through fecal transplant has been proven as a valid therapeutic strategy in diseases such as Clostridium difficile infections. Therefore, techniques to modulate the skin microbiome composition may become an interesting therapeutic option in diseases affecting the skin such as psoriasis or acne vulgaris.<br><br>METHODS: Here, we have used mixtures of different skin microbiome components to alter the composition of recipient skin microbiomes.<br><br>RESULTS: We show that after sequential applications of a donor microbiome, the recipient microbiome becomes more similar to the donor. After intervention, an initial week-long phase is characterized by the dominance of donor strains. The level of engraftment depends on the composition of the recipient and donor microbiomes, and the applied bacterial load. We observed higher engraftment using a multi-strain donor solution with recipient skin rich in Cutibacterium acnes subtype H1 and Leifsonia.<br><br>CONCLUSIONS: We have demonstrated the use of living bacteria to modulate skin microbiome composition.}, }
@article {pmid31232087, year = {2020}, author = {Qi, X and Zhang, Y and Guo, H and Hai, Y and Luo, Y and Yue, T}, title = {Mechanism and intervention measures of iron side effects on the intestine.}, journal = {Critical reviews in food science and nutrition}, volume = {60}, number = {12}, pages = {2113-2125}, doi = {10.1080/10408398.2019.1630599}, pmid = {31232087}, issn = {1549-7852}, mesh = {Antioxidants/metabolism ; Humans ; Intestines/*microbiology/*pathology ; Iron/*adverse effects/*metabolism ; Lipid Peroxidation/drug effects ; Oxidative Stress/drug effects ; }, abstract = {Excess oral iron in the intestinal tract usually produces reactive oxygen species via Fenton and Haber-Weiss reaction, so oxidative stress is triggered. Lipid peroxidation procedurally appears, ferroptosis, apoptosis and necrosis are often induced, subsequently, mitochondrial damage, endoplasmic reticulum dysfunction and even cell death occur. As a result, the intestinal epithelial cells are destroyed, leading to the incompleteness of intestinal mechanical barrier. Simultaneously, iron supplement can change the compositions and metabolic processes of intestinal microbes, and the intestinal inflammatory may be worsened. In principle, the easier dissociation of Fe[2+] from oral iron supplements is, the more serious intestinal inflammation will occur. Fortunately, some interventions have been developed to alleviate these side effects. For instance, some antioxidants e.g. VE and ferulic acid have been used to prevent the formation of free radicals or to neutralize the formed free radicals. Furthermore, some new iron supplements with the ability of slow-releasing Fe[2+], e.g. ferrous citrate liposome and EDTA iron sodium, have been successfully prepared. In order to recover the intestinal micro-ecological balance, probiotics and prebiotics, bacterial consortium transplantation, and fecal microbiota transplantation have been developed. This study is meaningful for us to develop safer oral iron supplements and to maintain intestinal micro-ecological health.}, }
@article {pmid31231707, year = {2019}, author = {Kellermayer, R}, title = {Fecal microbiota transplantation: great potential with many challenges.}, journal = {Translational gastroenterology and hepatology}, volume = {4}, number = {}, pages = {40}, pmid = {31231707}, issn = {2415-1289}, abstract = {In January of 2019, Samuel P. Costello and colleagues published a wonderfully executed, double blind placebo-controlled trial on fecal microbiota transplantation (FMT) versus autologous stool as placebo in mild to moderately active adult ulcerative colitis [UC: one type of inflammatory bowel disease (IBD)] patients. This review-commentary examines the current state of knowledge on human gut microbiome (live microbiota + their products and surrounding environment, i.e., fecal matter) and microbial therapeutics from a gastrointestinal (GI) clinician's standpoint. The varied forms of dysbiosis as the target of FMT, recipient donor and placebo considerations are also discussed in respect to randomized control trials in IBD [and the lack thereof in Crohn's disease (CD)] with this unconventional treatment modality.}, }
@article {pmid31222022, year = {2019}, author = {Burz, SD and Abraham, AL and Fonseca, F and David, O and Chapron, A and Béguet-Crespel, F and Cénard, S and Le Roux, K and Patrascu, O and Levenez, F and Schwintner, C and Blottière, HM and Béra-Maillet, C and Lepage, P and Doré, J and Juste, C}, title = {A Guide for Ex Vivo Handling and Storage of Stool Samples Intended for Fecal Microbiota Transplantation.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {8897}, pmid = {31222022}, issn = {2045-2322}, mesh = {Cryoprotective Agents ; *Fecal Microbiota Transplantation ; *Feces ; *Guidelines as Topic ; Humans ; Polysaccharides ; Specimen Handling/*methods ; Trehalose ; }, abstract = {Owing to the growing recognition of the gut microbiota as a main partner of human health, we are expecting that the number of indications for fecal microbiota transplantation (FMT) will increase. Thus, there is an urgent need for standardization of the entire process of fecal transplant production. This study provides a complete standardized procedure to prepare and store live and ready-to-use transplants that meet the standard requirements of good practices to applied use in pharmaceutical industry. We show that, if time before transformation to transplants would exceed 24 hours, fresh samples should not be exposed to temperatures above 20 °C, and refrigeration at 4 °C can be a safe solution. Oxygen-free atmosphere was not necessary and simply removing air above collected samples was sufficient to preserve viability. Transplants prepared in maltodextrin-trehalose solutions, stored in a -80 °C standard freezer and then rapidly thawed at 37 °C, retained the best revivification potential as proven by 16S rRNA profiles, metabolomic fingerprints, and flow cytometry assays over a 3-month observation period. Maltodextrin-trehalose containing cryoprotectants were also efficient in preserving viability of lyophilized transplants, either in their crude or purified form, an option that can be attractive for fecal transplant biobanking and oral formulation.}, }
@article {pmid31221971, year = {2019}, author = {Frisbee, AL and Saleh, MM and Young, MK and Leslie, JL and Simpson, ME and Abhyankar, MM and Cowardin, CA and Ma, JZ and Pramoonjago, P and Turner, SD and Liou, AP and Buonomo, EL and Petri, WA}, title = {IL-33 drives group 2 innate lymphoid cell-mediated protection during Clostridium difficile infection.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {2712}, pmid = {31221971}, issn = {2041-1723}, support = {R21 AI114734/AI/NIAID NIH HHS/United States ; T32 AI007496/AI/NIAID NIH HHS/United States ; 1R21AI114734//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/International ; 5R01AI124214-02//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/International ; F31 AI136421/AI/NIAID NIH HHS/United States ; R01 AI124214/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Anti-Bacterial Agents/adverse effects ; Bacterial Toxins/immunology/metabolism ; Clostridioides difficile/*immunology/pathogenicity ; Colon/cytology/immunology/microbiology/pathology ; Disease Models, Animal ; Enterocolitis, Pseudomembranous/*immunology/microbiology/mortality/therapy ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/drug effects/immunology ; Gene Expression Profiling ; Humans ; *Immunity, Innate ; Interleukin-33/immunology/*metabolism ; Lymphocytes/*immunology/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Up-Regulation/drug effects/immunology ; Virulence/immunology ; Young Adult ; }, abstract = {Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C. difficile toxins cause damaging colonic inflammation, the immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an immune target upregulated in response to hypervirulent C. difficile. We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disruption independently of bacterial burden or toxin expression. IL-33 drives colonic group 2 innate lymphoid cell (ILC2) activation during infection and IL-33 activated ILC2s are sufficient to prevent disease. Furthermore, intestinal IL-33 expression is regulated by the microbiota as fecal microbiota transplantation (FMT) rescues antibiotic-associated depletion of IL-33. Lastly, dysregulated IL-33 signaling via the decoy receptor, sST2, predicts C. difficile-associated mortality in human patients. Thus, IL-33 signaling to ILC2s is an important mechanism of defense from C. difficile colitis.}, }
@article {pmid31220424, year = {2019}, author = {D'Haens, GR and Jobin, C}, title = {Fecal Microbial Transplantation for Diseases Beyond Recurrent Clostridium Difficile Infection.}, journal = {Gastroenterology}, volume = {157}, number = {3}, pages = {624-636}, pmid = {31220424}, issn = {1528-0012}, support = {R01 AT008623/AT/NCCIH NIH HHS/United States ; R01 DK073338/DK/NIDDK NIH HHS/United States ; R21 CA195226/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Central Nervous System Diseases/diagnosis/microbiology/*therapy ; Clostridium Infections/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Diseases/diagnosis/microbiology/*therapy ; *Gastrointestinal Microbiome ; Humans ; Inflammation/diagnosis/microbiology/*therapy ; Recurrence ; Treatment Outcome ; }, abstract = {As microbiome research has moved from associative to mechanistic studies, the activities of specific microbes and their products have been investigated in the development of inflammatory bowel diseases, cancer, metabolic syndrome, and neuropsychiatric disorders. Findings from microbiome research have already been applied to the clinic, such as in fecal microbiota transplantation for treatment of recurrent Clostridium difficile infection. We review the evidence for associations between alterations in the intestinal microbiome and gastrointestinal diseases and findings from clinical trials of fecal microbiota transplantation. We discuss opportunities for treatment of other diseases with fecal microbiota transplantation, based on findings from small clinical and preclinical studies.}, }
@article {pmid31220352, year = {2020}, author = {Liu, R and Kang, JD and Sartor, RB and Sikaroodi, M and Fagan, A and Gavis, EA and Zhou, H and Hylemon, PB and Herzog, JW and Li, X and Lippman, RH and Gonzalez-Maeso, J and Wade, JB and Ghosh, S and Gurley, E and Gillevet, PM and Bajaj, JS}, title = {Neuroinflammation in Murine Cirrhosis Is Dependent on the Gut Microbiome and Is Attenuated by Fecal Transplant.}, journal = {Hepatology (Baltimore, Md.)}, volume = {71}, number = {2}, pages = {611-626}, pmid = {31220352}, issn = {1527-3350}, support = {P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; I01 CX001076/CX/CSRD VA/United States ; I01 BX001390/BX/BLRD VA/United States ; R01 MH111940/MH/NIMH NIH HHS/United States ; R01 DK087913/DK/NIDDK NIH HHS/United States ; R01 MH084894/MH/NIMH NIH HHS/United States ; R56 MH084894/MH/NIMH NIH HHS/United States ; R01 DK115377/DK/NIDDK NIH HHS/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; I01 BX004033/BX/BLRD VA/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; I01 BX001328/BX/BLRD VA/United States ; P01 DK094779/DK/NIDDK NIH HHS/United States ; R21 AA026629/AA/NIAAA NIH HHS/United States ; IK6 BX004477/BX/BLRD VA/United States ; R01 DK104893/DK/NIDDK NIH HHS/United States ; R01 DK057543/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Cerebral Cortex ; Dysbiosis/*complications ; Encephalitis/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Liver Cirrhosis/*microbiology/*therapy ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {Cirrhosis and hepatic encephalopathy (HE) is associated with an altered gut-liver-brain axis. Fecal microbial transplant (FMT) after antibiotics improves outcomes in HE, but the impact on brain function is unclear. The aim of this study is to determine the effect of colonization using human donors in germ-free (GF) mice on the gut-liver-brain axis. GF and conventional mice were made cirrhotic using carbon tetrachloride and compared with controls in GF and conventional state. Additional GF mice were colonized with stool from controls (Ctrl-Hum) and patients with cirrhosis (Cirr-Hum). Stools from patients with HE cirrhosis after antibiotics were pooled (pre-FMT). Stools from the same patients 15 days after FMT from a healthy donor were also pooled (post-FMT). Sterile supernatants were created from pre-FMT and post-FMT samples. GF mice were colonized using stools/sterile supernatants. For all mice, frontal cortex, liver, and small/large intestines were collected. Cortical inflammation, synaptic plasticity and gamma-aminobutyric acid (GABA) signaling, and liver inflammation and intestinal 16s ribosomal RNA microbiota sequencing were performed. Conventional cirrhotic mice had higher degrees of neuroinflammation, microglial/glial activation, GABA signaling, and intestinal dysbiosis compared with other groups. Cirr-Hum mice had greater neuroinflammation, microglial/glial activation, and GABA signaling and lower synaptic plasticity compared with Ctrl-Hum mice. This was associated with greater dysbiosis but no change in liver histology. Pre-FMT material colonization was associated with neuroinflammation and microglial activation and dysbiosis, which was reduced significantly with post-FMT samples. Sterile pre-FMT and post-FMT supernatants did not affect brain parameters. Liver inflammation was unaffected. Conclusion: Fecal microbial colonization from patients with cirrhosis results in higher degrees of neuroinflammation and activation of GABAergic and neuronal activation in mice regardless of cirrhosis compared with those from healthy humans. Reduction in neuroinflammation by using samples from post-FMT patients to colonize GF mice shows a direct effect of fecal microbiota independent of active liver inflammation or injury.}, }
@article {pmid31219825, year = {2019}, author = {Knudsen, C and Neyrinck, AM and Lanthier, N and Delzenne, NM}, title = {Microbiota and nonalcoholic fatty liver disease: promising prospects for clinical interventions?.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {22}, number = {5}, pages = {393-400}, doi = {10.1097/MCO.0000000000000584}, pmid = {31219825}, issn = {1473-6519}, mesh = {Animals ; Biomedical Research ; Disease Progression ; Gastrointestinal Microbiome/*physiology ; Humans ; Metabolomics ; Metagenomics ; Mice ; *Non-alcoholic Fatty Liver Disease/physiopathology/therapy ; Rats ; }, abstract = {PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is becoming the most important cause of chronic liver disease in Western countries but no pharmacological therapy is currently available. Growing evidence suggests that the microbiota plays a role in the occurrence and evolution of this disease, namely through the production of bioactive metabolites.<br><br>RECENT FINDINGS: Omics technologies (metagenomic, metabolomic, and phenomic data) allow providing a robust prediction of steatosis. More than just correlations, causative effects of certain bacterial metabolites have been evidenced in vitro and in rodent models. Butyrate has been shown to be a potent metabolic and inflammatory modulator in the liver. Several aromatic amino-acids such as phenylacetic acid, imidazole propionate, and 3-(4-hydroxyphenyl)lactate have been identified as potential inducers of steatosis and hepatic inflammation, whereas indolic compounds (indole and indole-3-acetate) seem to preserve liver integrity. Current clinical trials aim at evaluating the efficacy of novel approaches (functional foods, prebiotic and probiotics, and fecal microbial transplants).<br><br>SUMMARY: The microbiota brings new hopes in the management of nonalcoholic fatty liver diseases, including nonalcoholic steatohepatitis. Adequate intervention studies in targeted patients are needed to unravel the relevance of such approaches in the management of those liver diseases.}, }
@article {pmid31218940, year = {2019}, author = {Jagessar, SAR and Long, C and Cui, B and Zhang, F}, title = {Improvement of Good's syndrome by fecal microbiota transplantation: the first case report.}, journal = {The Journal of international medical research}, volume = {47}, number = {7}, pages = {3408-3415}, pmid = {31218940}, issn = {1473-2300}, mesh = {Aged ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Immunologic Deficiency Syndromes/*therapy ; Prognosis ; Thymoma/*therapy ; Thymus Neoplasms/*therapy ; }, abstract = {Good’s syndrome (GS) is a rare primary immunodeficiency defined as hypogammaglobulinemia associated with the presence of a thymoma. Patients with GS usually have increased susceptibility to a wide range of infections, and clinical treatment is a challenge for physicians. Fecal microbiota transplantation (FMT), which is a safe strategy for reconstruction of the gut microbiota, has a positive influence on the treatment of refractory infections such as those in patients with GS. We herein report a case involving a 73-year-old woman who had been previously diagnosed with a thymoma. After thymectomy, she complained of respiratory and gastrointestinal symptoms. Her laboratory analysis strongly suggested GS. Infusion of immunoglobulin and albumin was the only treatment of choice until FMT was considered as an alternative therapy. The patient’s manifestations were subsequently relieved, and several FMTs were required to maintain clinical remission. Management of GS remains quite challenging to physicians because of the intricate organ involvement and limited and costly existing therapies. FMT is usually well tolerated by patients, and its cost-effectiveness and safety profile allow it to be considered as an alternative therapy for GS.}, }
@article {pmid31215020, year = {2019}, author = {Gupta, S and Basu, S and Bal, V and Rath, S and George, A}, title = {Gut IgA abundance in adult life is a major determinant of resistance to dextran sodium sulfate-colitis and can compensate for the effects of inadequate maternal IgA received by neonates.}, journal = {Immunology}, volume = {158}, number = {1}, pages = {19-34}, pmid = {31215020}, issn = {1365-2567}, mesh = {Animals ; Animals, Newborn ; Bacteria/*immunology ; Bacterial Load ; Colitis/chemically induced/immunology/microbiology/*prevention &amp; control ; Colon/immunology/metabolism/*microbiology ; Crosses, Genetic ; *Dextran Sulfate ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; Immunoglobulin A/*immunology/metabolism ; Inflammation Mediators/immunology/metabolism ; Lactation ; Male ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Inbred DBA ; Permeability ; Pregnancy ; Species Specificity ; }, abstract = {Studies with gene-deficient and gnotobiotic mice have identified many host and microbial factors that contribute to induced colitis, but information on whether specific factors determine susceptibility under more physiological conditions is lacking. Using wild-type strains that differ in their IgA response but harbor a diverse gut microbiome, we found that the IgA-high strain CBA/CaJ (CBA) is resistant to acute colitis induced with dextran sodium sulfate (DSS), unlike the IgA-low strain C57BL/6 (B6). Resistance was associated with extensive IgA-coating of fecal bacteria, lower fecal bacterial loads and greater abundance of barrier-protective transcripts in colonic tissues under homeostatic conditions. Fecal microbial transplant (FT) experiments revealed that disease induction in B6 mice was associated with a cohort of bacteria that are not targeted by IgA. However, CBA mice continued to be resistant to colitis induction following FTs from B6 mice, indicating that they are able to contain such colitogenic members. In support of a role for bacterial exclusion in resistance, oral administration of immunoglobulins decreased DSS-induced disease in B6 mice. In F1 mice derived separately with CBA and B6 dams and in F1 mice backcrossed to the two parental strains, resistance segregated with the IgA response of the pups and not with barrier-associated transcripts or bacterial loads. Interestingly, B6 pups foster-nursed on CBA dams continued to be susceptible in later life, whereas CBA pups foster-nursed on B6 dams continued to be resistant. Together, the data indicate that a high-IgA response in adult life can protect against colitis and compensate for IgA deficiency in early life.}, }
@article {pmid31212833, year = {2019}, author = {Foligné, B and Plé, C and Titécat, M and Dendooven, A and Pagny, A and Daniel, C and Singer, E and Pottier, M and Bertin, B and Neut, C and Deplanque, D and Dubuquoy, L and Desreumaux, P and Capron, M and Standaert, A}, title = {Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights.}, journal = {Cells}, volume = {8}, number = {6}, pages = {}, pmid = {31212833}, issn = {2073-4409}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Anti-Inflammatory Agents/*therapeutic use ; Colitis/chemically induced/microbiology/prevention &amp; control/therapy ; Crohn Disease/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Glutathione Transferase/*therapeutic use ; Humans ; Immunization ; Immunomodulation ; Mice, Inbred BALB C ; Phenotype ; Trinitrobenzenesulfonic Acid ; }, abstract = {An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn's disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn's disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules.}, }
@article {pmid31212328, year = {2019}, author = {Reisinger, EC and Ebbers, M and Löbermann, M}, title = {[Clostridium Difficile: Monoclonal Antibody Therapy and Vaccines].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {144}, number = {12}, pages = {842-849}, doi = {10.1055/a-0882-7530}, pmid = {31212328}, issn = {1439-4413}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Antibodies, Monoclonal/*therapeutic use ; Antibodies, Neutralizing/*therapeutic use ; Bacterial Vaccines/*therapeutic use ; Broadly Neutralizing Antibodies ; Clostridioides difficile/immunology ; *Clostridium Infections/immunology/microbiology/prevention &amp; control/therapy ; Fecal Microbiota Transplantation ; Humans ; Middle Aged ; }, abstract = {Hospital-acquired Clostridium difficile infections have become much more frequent in recent years. Besides treatment with antibiotics and fecal microbiota transplant, new preventive strategies are available now. Bezlotoxumab is an antibody against toxin B and may reduce the risk of relapse by roughly 10 %. Several vaccine candidates against toxins A and B and surface-associated antigens were immunogenic and are tested in clinical trials to investigate the efficacy and safety.}, }
@article {pmid31212145, year = {2019}, author = {Ponti, G and Manfredini, M and Tomasi, A}, title = {Non-blood sources of cell-free DNA for cancer molecular profiling in clinical pathology and oncology.}, journal = {Critical reviews in oncology/hematology}, volume = {141}, number = {}, pages = {36-42}, doi = {10.1016/j.critrevonc.2019.06.005}, pmid = {31212145}, issn = {1879-0461}, mesh = {Biomarkers, Tumor/analysis/*genetics/isolation &amp; purification ; Cell-Free Nucleic Acids/analysis/*isolation &amp; purification ; Circulating Tumor DNA/analysis/isolation &amp; purification/urine ; DNA Mutational Analysis/methods ; Feces/chemistry ; Female ; Gene Expression Profiling/*methods ; Humans ; Liquid Biopsy ; Male ; Medical Oncology/*methods/trends ; Neoplasms/*diagnosis/genetics/pathology/urine ; Pathology, Clinical/*methods ; Prostatic Neoplasms/diagnosis/metabolism/therapy ; Urinalysis/methods ; }, abstract = {Liquid biopsy can quantify and qualify cell-free (cfDNA) and tumour-derived (ctDNA) DNA fragments in the bloodstream. CfDNA quantification and mutation analysis can be applied to diagnosis, follow-up and therapeutic management as novel oncologic biomarkers. However, some tumor-types release a low amount of DNA into the bloodstream, hampering diagnosis through standard liquid biopsy procedures. Several tumors, as such as brain, kidney, prostate, and thyroid cancer, are in direct contact with other body fluids and may be alternative sources for cfDNA and ctDNA. Non-blood sources of cfDNA/ctDNA useful as novel oncologic biomarkers include cerebrospinal fluids, urine, sputum, saliva, pleural effusion, stool and seminal fluid. Seminal plasma cfDNA, which can be analyzed with cost-effective procedures, may provide powerful information capable to revolutionize prostate cancer (PCa) patient diagnosis and management. In the near future, cfDNA analysis from non-blood biological liquids will become routine clinical practice for cancer patient diagnosis and management.}, }
@article {pmid31211801, year = {2019}, author = {Mejido, DCP and de Oliveira, JM and Gaspar, AMC and Gardinali, NR and Bottino, FO and de Carvalho, LG and Lopes Dos Santos, DR and Kevorkian, YB and Xavier, LL and Moran, J and Pelajo-Machado, M and Marchevsky, RS and Pinto, MA}, title = {Evidences of HEV genotype 3 persistence and reactivity in liver parenchyma from experimentally infected cynomolgus monkeys (Macaca fascicularis).}, journal = {PloS one}, volume = {14}, number = {6}, pages = {e0218472}, pmid = {31211801}, issn = {1932-6203}, mesh = {Animals ; Disease Models, Animal ; Duodenum/pathology/virology ; Feces/virology ; Gallbladder/pathology/virology ; Genotype ; Hepatitis Antibodies/genetics/immunology ; Hepatitis E/*genetics/immunology/pathology/virology ; Hepatitis E virus/*genetics/immunology/pathogenicity ; Humans ; Liver/pathology/*virology ; Macaca fascicularis/immunology/*virology ; Parenchymal Tissue/pathology/virology ; Spleen/pathology/virology ; Swine/virology ; Virion/genetics/immunology/pathogenicity ; }, abstract = {Hepatitis E virus genotype 3 (HEV-3) is an emerging zoonotic pathogen, responsible for sporadic cases of acute hepatitis E worldwide. Primate models have proven to be an essential tool for the study of HEV pathogenesis. Here we describe the outcomes of HEV infection in Macaca fascicularis (cynomolgus) inoculated experimentally with genotype 3. Eight adult cynomolgus macaques were inoculated intravenously with HEV-3 viral particles isolated from swine and human samples. Liver, spleen, duodenum, gallbladder and bile were sequential assessed up to the end-point of this study, 67 days post-inoculation (dpi). Our previously published findings showed that biochemical parameters return gradually to baseline levels at 55 dpi, whereas anti-HEV IgM and HEV RNA become undetectable in the serum and feces of all animals, indicating a non-viremic phase of recovery. Nevertheless, at a later stage during convalescence (67 dpi), the presence of HEV-3 RNA and antigen persist in central organs, even after peripheral viral clearance. Our results show that two cynomolgus inoculated with swine HEV-3 (animals I3 and O1) presented persistence of HEV RNA low titers in liver, gallbladder and bile. At this same stage of infection, HEV antigen (HEV Ag) could be detected in all infected animals, predominantly in non-reactive Kupffer cells (CD68+iNOS-) and sinusoidal lining cells. Simultaneously, CD4+, CD3+CD4+, and CD3+CD8+ immune cells were identified in hepatic sinusoids and small inflammatory clusters of lobular mononuclear cells, at the end-point of this study. Inability of HEV clearance in humans can result in chronic hepatitis, liver cirrhosis, with subsequent liver failure requiring transplantation. The results of our study support the persistence of HEV-3 during convalescence at 67 dpi, with active immune response in NHP. We alert to the inherent risk of viral transmission through liver transplantation, even in the absence of clinical and biochemical signs of acute infection. Thus, besides checking conventional serological markers of HEV infection, we strongly recommend HEV-3 RNA and antigen detection in liver explants as public health measure to prevent donor-recipient transmission and spread of hepatitis E.}, }
@article {pmid31211700, year = {2019}, author = {Mishima, Y and Oka, A and Liu, B and Herzog, JW and Eun, CS and Fan, TJ and Bulik-Sullivan, E and Carroll, IM and Hansen, JJ and Chen, L and Wilson, JE and Fisher, NC and Ting, JP and Nochi, T and Wahl, A and Garcia, JV and Karp, CL and Sartor, RB}, title = {Microbiota maintain colonic homeostasis by activating TLR2/MyD88/PI3K signaling in IL-10-producing regulatory B cells.}, journal = {The Journal of clinical investigation}, volume = {129}, number = {9}, pages = {3702-3716}, pmid = {31211700}, issn = {1558-8238}, support = {R01 CA156330/CA/NCI NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; R01 AI123010/AI/NIAID NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 AI140799/AI/NIAID NIH HHS/United States ; R01 DK053347/DK/NIDDK NIH HHS/United States ; R01 AI111899/AI/NIAID NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; R01 MH108179/MH/NIMH NIH HHS/United States ; P01 DK094779/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; B-Lymphocytes, Regulatory/immunology/*microbiology ; Colitis/microbiology ; Cytokines/metabolism ; Down-Regulation ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Germ-Free Life ; Green Fluorescent Proteins/metabolism ; Immunity, Innate ; Inflammation ; Interleukin-10/*metabolism ; Intestines/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88/*metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Toll-Like Receptor 2/*metabolism ; Toll-Like Receptor 9/metabolism ; }, abstract = {Resident microbiota activate regulatory cells that modulate intestinal inflammation and promote and maintain intestinal homeostasis. IL-10 is a key mediator of immune regulatory function. Our studies described the functional importance and mechanisms by which gut microbiota and specific microbial components influenced the development of intestinal IL-10-producing B cells. We used fecal transplant to germ-free (GF) Il10+/EGFP reporter and Il10-/- mice to demonstrate that microbiota from specific pathogen-free mice primarily stimulated IL-10-producing colon-specific B cells and T regulatory-1 cells in ex-GF mice. IL-10 in turn down-regulated microbiota-activated mucosal inflammatory cytokines. TLR2/9 ligands and enteric bacterial lysates preferentially induced IL-10 production and regulatory capacity of intestinal B cells. Analysis of Il10+/EGFP mice crossed with additional gene-deficient strains and B cell co-transfer studies demonstrated that microbiota-induced IL-10-producing intestinal B cells ameliorated chronic T cell-mediated colitis in a TLR2, MyD88 and PI3K-dependent fashion. In vitro studies implicated PI3Kp110δ and AKT downstream signaling. These studies demonstrated that resident enteric bacteria activated intestinal IL-10-producing B cells through TLR2, MyD88 and PI3K pathways. These B cells reduced colonic T cell activation and maintained mucosal homeostasis in response to intestinal microbiota.}, }
@article {pmid31210950, year = {2019}, author = {Peri, R and Aguilar, RC and Tüffers, K and Erhardt, A and Link, A and Ehlermann, P and Angeli, W and Frank, T and Storr, M and Glück, T and Sturm, A and Rosien, U and Tacke, F and Bachmann, O and Solbach, P and Stallmach, A and Goeser, F and Vehreschild, MJ and , }, title = {The impact of technical and clinical factors on fecal microbiota transfer outcomes for the treatment of recurrent Clostridioides difficile infections in Germany.}, journal = {United European gastroenterology journal}, volume = {7}, number = {5}, pages = {716-722}, pmid = {31210950}, issn = {2050-6406}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; *Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Secondary Prevention ; Treatment Failure ; }, abstract = {INTRODUCTION: Fecal microbiota transfer (FMT) is highly effective in the treatment and prevention of recurrent Clostridioides difficile infection (rCDI) with cure rates of about 80% after a single treatment. Nevertheless, the reasons for failure in the remaining 20% remain largely elusive. The aim of the present study was to investigate different potential clinical predictors of response to FMT in Germany.<br><br>METHODS: Information was extracted from the MicroTrans Registry (NCT02681068), a retrospective observational multicenter study, collecting data from patients undergoing FMT for recurrent or refractory CDI in Germany. We performed binary logistic regression with the following covariates: age, gender, ribotype 027, Eastern Co-operative Oncology Group score, immunosuppression, preparation for FMT by use of proton pump inhibitor, antimotility agents and bowel lavage, previous recurrences, severity of CDI, antibiotic induction treatment, fresh or frozen FMT preparation, and route of application.<br><br>RESULTS: Treatment response was achieved in 191/240 evaluable cases (79.6%) at day 30 (D30) post FMT and 78.1% at day 90 (D90) post FMT. Assessment of clinical predictors for FMT failure by forward and confirmatory backward-stepwise regression analysis yielded higher age as an independent predictor of FMT failure (p&#x2009;=&#x2009;0.001; OR 1.060; 95%CI 1.025-1.097).<br><br>CONCLUSION: FMT in Germany is associated with high cure rates at D30 and D90. No specific pre-treatment, preparation or application strategy had an impact on FMT success. Only higher age was identified as an independent risk factor for treatment failure. Based on these and external findings, future studies should focus on the assessment of microbiota and microbiota-associated metabolites as factors determining FMT success.}, }
@article {pmid31208713, year = {2019}, author = {Kalinkovich, A and Livshits, G}, title = {A cross talk between dysbiosis and gut-associated immune system governs the development of inflammatory arthropathies.}, journal = {Seminars in arthritis and rheumatism}, volume = {49}, number = {3}, pages = {474-484}, doi = {10.1016/j.semarthrit.2019.05.007}, pmid = {31208713}, issn = {1532-866X}, mesh = {Arthritis/etiology/*immunology ; Dysbiosis/*complications/immunology ; *Gastrointestinal Microbiome ; Humans ; *Immunity, Innate ; }, abstract = {BACKGROUND: Emerging evidence suggests that dysbiosis, imbalanced gut microbial community, might be a key player in the development of various diseases, including inflammatory arthropathies, such as rheumatoid arthritis, spondyloarthritis (mainly, ankylosing spondylitis and psoriatic arthritis), and osteoarthritis. Yet, the underlying mechanisms and corresponding interactions remain poorly understood.<br><br>METHODS: We conducted a critical and extensive literature review to explore the association between dysbiosis and the development of inflammatory arthropathies. We also reviewed the literature to assess the perspectives that ameliorate inflammatory arthropathies by manipulating the microbiota with probiotics, prebiotics or fecal microbiota transplantation.<br><br>RESULTS: Some bacterial species (e.g. Prevotella, Citrobacter rodentium, Collinsella aerofaciens, Segmented filamentous bacteria) participate in the creation of the pro-inflammatory immune status, presumably via epitope mimicry, modification of self-antigens, enhanced cell apoptosis mechanisms, and destruction of tight junction proteins and intestinal barrier integrity, all leading to the development and maintainance of inflammatory arthropathies. Whether dysbiosis is an epiphenomenon or is an active driver of these disorders remains unclear, yet, recent observations clearly suggest that dysbiosis precedes and triggers their development implying a causative relationship between dysbiosis and inflammatory arthropathies. The underlying mechanisms include dysbiosis-mediated changes in the functional activity of the intestinal immune cell subsets, such as innate lymphoid cells, mucosa-associated invariant T cells, invariant natural killer T cells, T-follicular helper and T-regulatory cells. In turn, disturbed functionality of the gut-associated immune system is shown to promote the overgrowth of many bacteria, thus establishing a detrimental vicious circle of actively maintaining arthritis.<br><br>CONCLUSIONS: Analysis of the data described in the review supports the notion that a close, dynamic and tightly regulated cross talk between dysbiosis and the gut-associated immune system governs the development of inflammatory arthropathies.}, }
@article {pmid31205420, year = {2019}, author = {Viggiani, MT and Di Leo, A and Barone, M}, title = {Can the Antisecretory Factor Be Considered a New Therapy for the Short Bowel Syndrome?.}, journal = {Nutrition and metabolic insights}, volume = {12}, number = {}, pages = {1178638819852061}, pmid = {31205420}, issn = {1178-6388}, abstract = {BACKGROUND AND OBJECTIVE: The antisecretory factor (AF) exerts antisecretory and anti-inflammatory properties in the bowel. The aim of this study was to evaluate the effect of exogenous AF (Salovum) or cereals stimulating the endogenous AF (SPC-Flakes), given alone or in combination, in patients with short bowel syndrome (SBS).<br><br>METHODS: Patients received Salovum alone at T0&#x2009;-T1, Salovum plus SPC-Flakes at T1&#x2009;-T2, and SPC-Flakes alone at T2&#x2009;-T3. At T0 and T3, water balance, weight, lean mass (FFM), total body water (TBW), extracellular water (ECW), and nutritional and inflammatory biochemical parameters were evaluated. The water balance was also measured at T1, T2, and 30&#x2009;days (TS) from the end of treatment.<br><br>RESULTS: Among the 7 patients enrolled, 2 discontinued treatment due to side effects and 1 was excluded after a cancer was diagnosed. Salovum alone or with SPC-Flakes did not improve the intestinal absorption in patients with SBS, while the administration of SPC-Flakes alone lead towards a trend of increased faecal volume. Weight, FFM, TBW, and ECW, as well as nutritional and inflammatory status, did not statistically change at the end of treatment (T3) as compared with T0. At TS water balance was restored.<br><br>CONCLUSION: The administration of exogenous AF or the stimulation of endogenous AF seems to be unable to offer an effective therapy in patients with SBS. On the contrary, their administration appears to aggravate fluid loss and induce side effects.}, }
@article {pmid31205257, year = {2020}, author = {Duclaux-Loras, R and Berthiller, J and Ferroni, A and Chardot, C and Goulet, O and Lacaille, F and Norsa, L}, title = {Clostridium difficile: A Frequent Infection in Children After Intestinal Transplantation.}, journal = {Transplantation}, volume = {104}, number = {1}, pages = {197-200}, doi = {10.1097/TP.0000000000002795}, pmid = {31205257}, issn = {1534-6080}, mesh = {Adolescent ; Anti-Bacterial Agents/therapeutic use ; Child ; Child, Preschool ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/drug therapy/*epidemiology/microbiology ; Cross-Sectional Studies ; Diarrhea/diagnosis/drug therapy/*epidemiology/microbiology ; Feces/microbiology ; Female ; Follow-Up Studies ; Humans ; Intestinal Mucosa/microbiology ; Intestine, Small/microbiology/*transplantation ; Male ; Metronidazole/therapeutic use ; Postoperative Complications/diagnosis/drug therapy/*epidemiology/microbiology ; Prevalence ; Recurrence ; Retrospective Studies ; Risk Factors ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Organ transplantation (Tx) is a risk factor for Clostridium difficile infection (CDI). After intestinal transplantation (ITx), few data are available on the impact of this graft infection and the possible induction of rejection.<br><br>METHODS: We included retrospectively all children after ITx in our unit, with at least 1 year of graft survival. All samples positive for Clostridium difficile (CD) and its toxin were considered.<br><br>RESULTS: Among the 57 ITx recipients (60 Txs), 22 children (39%) developed culture-proven CDI, 12 after isolated small bowel Tx, 9 after liver-small bowel Tx, and 1 after multivisceral Tx. Twenty patients had diarrhea, 8 bloody stools, 4 fever, and 1 hypothermia. Nine were hospitalized for an average of 6.5 days (2-20) and 4 with severe dehydration. Nine (40%) had received antibiotics for an average of 19 days (7-60) before CDI. Two patients were asymptomatic. CDI was treated with metronidazole in 12 children, vancomycin in 6, and both in 3. Three children presented mild-to-severe rejections. Two patients presented concomitantly CDI and rejection. The third patient presented a rejection with severe complications 4 years after CDI. Recurrence of toxinogenic CD was observed in 9 children, in 7 associated with clinical symptoms. During the last follow-up, the stool number was the same as before CDI except for 1 patient with ongoing infection.<br><br>CONCLUSIONS: CDI is more prevalent in children after ITx compared with other organ Tx; it is most often symptomatic but mildly or moderately severe. Standard antibiotics efficiently control the symptoms. Induction of rejection is a rare event.}, }
@article {pmid31205136, year = {2019}, author = {Ahamed, R and Philips, CA and Augustine, P}, title = {Fecal Microbiota Transplantation for Primary Sclerosing Cholangitis-A Beautiful but Incomplete Story.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {8}, pages = {1353-1354}, doi = {10.14309/ajg.0000000000000294}, pmid = {31205136}, issn = {1572-0241}, mesh = {*Cholangitis, Sclerosing ; Fecal Microbiota Transplantation ; Humans ; *Liver Transplantation ; *Pancreatitis, Chronic ; }, }
@article {pmid31205129, year = {2019}, author = {Khoruts, A and Brandt, LJ}, title = {Fecal Microbiota Transplant: A Rose by Any Other Name.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {7}, pages = {1176}, doi = {10.14309/ajg.0000000000000286}, pmid = {31205129}, issn = {1572-0241}, mesh = {Clostridioides difficile/pathogenicity ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces ; Forecasting ; Humans ; *Intestines ; *Terminology as Topic ; }, }
@article {pmid31204469, year = {2019}, author = {Wang, B and Zhang, L and Zhu, SW and Zhang, JD and Duan, LP}, title = {Short chain fatty acids contribute to gut microbiota-induced promotion of colonic melatonin receptor expression.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {33}, number = {3}, pages = {763-771}, pmid = {31204469}, issn = {0393-974X}, mesh = {Animals ; Caco-2 Cells ; Colon ; Fatty Acids, Volatile/*metabolism ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S ; Rats ; Receptors, Melatonin/*genetics ; }, abstract = {Melatonin plays an important role in various gut functions through melatonin receptors. The gut microbiota/gut hormone axis has recently received increasing attention. However, the relationship between the gut microbiota and melatonin receptors has not yet been evaluated. We aimed to determine the effect of the gut microbiota on colonic melatonin receptor expression in germ-free (GF) rats and to further explore the potential mechanism in Caco-2 cells. In this study, GF rats were transplanted with fecal samples from a healthy human donor. Subsequently, 16S rRNA sequencing was performed to analyze the microbial communities. Colon tissue was collected for immunohistochemical analysis. The correlations between melatonin receptor expression and the gut microbiota were assessed. Melatonin receptor expression in Caco-2 cells was detected by Western blot. We found that fecal microbiota transplantation significantly increased the expression of colonic melatonin receptors in GF rats. The amount of fecal Short chain fatty acids (SCFAs) was significantly higher in fecal microbiota transplantation (FMT) rats than in GF rats. SCFA-producing bacteria, such as Alistipes and Blautia, were positively correlated with colonic melatonin receptor expression in FMT rats. Additionally, acetate and propionate significantly increased melatonin receptor-1 expression in Caco-2 cells. Therefore, the gut microbiota may promote melatonin receptor expression, and the mechanism may involve the action of SCFAs. This finding may facilitate the development of new therapeutic treatments for various gastrointestinal disorders.}, }
@article {pmid31204202, year = {2019}, author = {Smirnova, DV and Zalomova, LV and Zagainova, AV and Makarov, VV and Mezhevikina, LM and Fesenko, EE and Yudin, SM}, title = {Cryopreservation of the human gut microbiota: Current state and perspectives.}, journal = {International journal of medical microbiology : IJMM}, volume = {309}, number = {5}, pages = {259-269}, doi = {10.1016/j.ijmm.2019.06.001}, pmid = {31204202}, issn = {1618-0607}, mesh = {Biological Specimen Banks ; Cryopreservation/*methods/standards ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Probiotics ; Specimen Handling ; }, abstract = {The human intestinal microbiota is a complex ecosystem that consists of thousands of bacterial species that are responsible for human health and disease. The intestinal microbiota is a natural resource for production of therapeutic and preventive medicals, such as probiotics and fecal transplants. Modern lifestyles have resulted in the extinction of evolutionally selected microbial populations upon exposure to environmental factors. Therefore, it is very important to preserve the human gut microbiota to have the opportunity for timely restoration with minimal safety risks. Cryopreservation techniques that are suitable for the preservation of viable, mixed microbial communities and a biobanking approach are currently under development in different countries. However, the number of studies in this area is very limited. The variety of morphological and physiological characteristics of microbes in the microbiota, the different cryopreservation goals, and the criteria for the evaluation of cryopreservation effectiveness are the main challenges in the creation of a universal and standardized cryopreservation protocol. In this review, we summarized the current progress of the main cryopreservation techniques for gut microbiota communities and the methods for the assessment of the effectiveness of these techniques in the context of practical application.}, }
@article {pmid31201994, year = {2019}, author = {Baron, SA and Cassir, N and Mékidèche, T and Mlaga, KD and Brouqui, P and Rolain, JM}, title = {Successful treatment and digestive decolonisation of a patient with osteitis caused by a carbapenemase-producing Klebsiella pneumoniae isolate harbouring both NDM-1 and OXA-48 enzymes.}, journal = {Journal of global antimicrobial resistance}, volume = {18}, number = {}, pages = {225-229}, doi = {10.1016/j.jgar.2019.06.001}, pmid = {31201994}, issn = {2213-7173}, mesh = {Adult ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Proteins/adverse effects/genetics/metabolism ; Carbapenems/therapeutic use ; Drug Resistance, Multiple, Bacterial/drug effects/genetics ; Fecal Microbiota Transplantation/methods ; Humans ; Klebsiella pneumoniae/enzymology/*genetics/*metabolism/pathogenicity ; Male ; Microbial Sensitivity Tests ; Osteitis/chemically induced/*microbiology/*therapy ; Plasmids/genetics ; Whole Genome Sequencing ; beta-Lactamases/adverse effects/*genetics/*metabolism ; }, abstract = {OBJECTIVES: Carbapenem resistance in Klebsiella pneumoniae is an increasing problem worldwide and infections caused by this bacterium can be difficult to treat. This study reported the case of a patient from Romania, who was hospitalised in Bulgaria after an accident trauma. He then came to France for treatment of an osteitis caused by a Klebsiella pneumoniae carrying both blaNDM-1 and blaOXA-48.<br><br>METHOD: The resistome of this extremely drug-resistant bacterium was analysed both with phenotypic (large antibiotic susceptibility testing) and genomic methods (genome sequencing). The genetic environment of the two carbapenemases was studied.<br><br>RESULTS: Klebsiella pneumoniae ST307 carrying both a blaNDM-1 and blaOXA-48 gene was located on two different plasmids: Inc L/M and IncFII. The patient was successfully treated by a combination of intravenous colistin (9 MUI, then 4.5 MUI bd), intravenous fosfomycin (4g tds) and oral doxycycline (100mg bd) for 3 months. Faecal microbiota transplantation was successfully conducted for stool carriage.<br><br>CONCLUSION: The ST307 type is becoming endemic in hospital environments and is frequently associated with carbapenem resistance. Treatment of infection caused by multidrug-resistant bacteria is a clinical challenge, and the use of old antibiotics associated with screening and decolonisation of the reservoirs can be an efficient therapeutic alternative.}, }
@article {pmid31201141, year = {2019}, author = {Wortelboer, K and Nieuwdorp, M and Herrema, H}, title = {Fecal microbiota transplantation beyond Clostridioides difficile infections.}, journal = {EBioMedicine}, volume = {44}, number = {}, pages = {716-729}, pmid = {31201141}, issn = {2352-3964}, mesh = {Animals ; Clostridioides difficile/*physiology ; Clostridium Infections/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Diseases/etiology/therapy ; *Gastrointestinal Microbiome ; Humans ; Immune System Diseases/etiology/therapy ; Mental Disorders/etiology/therapy ; Metabolic Diseases/etiology/therapy ; Nervous System Diseases/etiology/therapy ; }, abstract = {The importance of the commensal microbiota to human health and well-being has become increasingly evident over the past decades. From a therapeutic perspective, the popularity of fecal microbiota transplantation (FMT) to restore a disrupted microbiota and amend imbalances has increased. To date, most clinical experience with FMT originates from the treatment of recurrent or refractory Clostridioides difficile infections (rCDI), with resolution rates up to 90%. In addition to CDI, a role for the intestinal microbiome has been implicated in several disorders. FMT has been tested in several randomized controlled trials for the treatment of inflammatory bowel disease, irritable bowel disease and constipation with mixed results. FMT has also been explored for extra-gastrointestinal disorders such as metabolic syndrome, hepatic encephalopathy and graft-versus-host disease. With the exception of recurrent CDI, FMT is currently used in experimental settings only and should not yet be offered as standard care. In addition, it is critical to further standardize and optimize procedures for FMT preparation. This includes determination of active components of FMT to develop (personalized) approaches to treat disease.}, }
@article {pmid31197926, year = {2019}, author = {Wang, JW and Wang, YK and Zhang, F and Su, YC and Wang, JY and Wu, DC and Hsu, WH}, title = {Initial experience of fecal microbiota transplantation in gastrointestinal disease: A case series.}, journal = {The Kaohsiung journal of medical sciences}, volume = {35}, number = {9}, pages = {566-571}, doi = {10.1002/kjm2.12094}, pmid = {31197926}, issn = {2410-8650}, support = {MOHW107-TDU-B-212-113006//Ministry of Health and Welfare, Taiwan/ ; KMU105-5M01//Kaohsiung Medical University Hospital/ ; MOST108-2321-B-037-001//Ministry of Science and Technology/ ; }, mesh = {Adult ; Aged, 80 and over ; Colonoscopy ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Diseases/diagnostic imaging/*therapy ; Humans ; Male ; Tissue Donors ; }, abstract = {Current studies have proven the strong association between gut microbiota dysbiosis and the pathogenesis of gastrointestinal diseases. Fecal microbiota transplantation (FMT) from a healthy donor is a promising therapeutic strategy to change and restore composition of the recipient's gut microbiota. Rapidly increasing clinical literatures confirmed the truth of the benefits of FMT on recurrent Clostridium difficile infection (rCDI) and inflammatory bowel disease. This article retrospectively reviewed nine cases (four cases had ulcerative colitis [UC], five cases had rCDI) who received FMT in Kaohsiung Medical University Hospital from April 2016 to November 2018. We summarized the procedure including donor selection, fecal materials preparation, transplantation delivery methods, and clinical outcomes. All of the four UC cases got clinical improvement and four rCDI cases achieved clinical remission after FMT. The other one rCDI case remained positive stool Toxin A+B result after FMT, and got remission after salvage treatment with fidaxomicin. FMT is considered to be a well-tolerated adjuvant treatment for UC and effective salvage treatment for rCDI in our initial experience. Multiple infusions of FMT in UC and rCDI might have exceptional clinical efficiency, and enteral tube insertion could be a useful method to reach this goal and make multiple sessions of FMT easier.}, }
@article {pmid31195433, year = {2019}, author = {Na, SY and Moon, W}, title = {Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease.}, journal = {Gut and liver}, volume = {13}, number = {6}, pages = {604-616}, pmid = {31195433}, issn = {2005-1212}, mesh = {Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*drug therapy ; Stem Cell Transplantation ; }, abstract = {New therapeutic strategies in inflammatory bowel disease (IBD) have shifted from symptom control towards treat-to-target algorithms in order to optimize treatment results. The treatment of IBD has evolved with the development of tumor necrosis factor-α inhibitors beyond the conventional therapies. In spite of their long-term effectiveness, many patients do not respond to or cannot sustain treatment with these drugs, which have various side effects. Therefore, the development of new drugs targeting specific pathways in the pathogenesis of IBD has become necessary. Some novel biologics and small molecule drugs have shown potential in IBD clinical trials, providing safe and effective results. In addition, clinicians are now trying to target the dysbiotic microbiome of patients with IBD using fecal microbiota transplantation. New tools such as stem cells have also been developed. The available therapeutic options for IBD are expanding rapidly. In the next few years, physicians will face an unprecedented number of options when choosing the best treatments for patients with IBD. This review provides an overview of recent advances in IBD treatment options.}, }
@article {pmid31193671, year = {2019}, author = {Smibert, OC and Guo, CW and Khoo, C and Thursky, KA and Sandhu, S and Slavin, MA}, title = {Microbiome transplantation and modulation of immune related adverse events.}, journal = {EClinicalMedicine}, volume = {8}, number = {}, pages = {10-11}, pmid = {31193671}, issn = {2589-5370}, }
@article {pmid31190948, year = {2019}, author = {Ilan, Y}, title = {Why targeting the microbiome is not so successful: can randomness overcome the adaptation that occurs following gut manipulation?.}, journal = {Clinical and experimental gastroenterology}, volume = {12}, number = {}, pages = {209-217}, pmid = {31190948}, issn = {1178-7023}, abstract = {The microbiome is explored as a potential target for therapy of bowel and systemic diseases. Fecal microbiota transplantation (FMT) has demonstrated efficacy in Clostridium difficile infection. However, clinical results regarding other diseases are modest, despite the abundant research on the microbiome over the last decade. Both high rate variability of the microbiome and adaptation to gut manipulations may underlie the lack of ultimate effects of FMT, probiotics, prebiotics, synbiotics, and antibiotics, which are aimed at restoring a healthier microbiome. The present review discusses the inherent variability of the microbiome and multiple factors that affect its diversity, as possible causes of the adaptation of the gut microbiome to chronic manipulation. The potential use of randomness is proposed, as a means of overcoming the adaptation and of restoring some of the inherent variability, with the goal of improving the long-term efficacy of these therapies.}, }
@article {pmid31190584, year = {2019}, author = {Mazzawi, T and Hausken, T and Hov, JR and Valeur, J and Sangnes, DA and El-Salhy, M and Gilja, OH and Hatlebakk, JG and Lied, GA}, title = {Clinical response to fecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels.}, journal = {Scandinavian journal of gastroenterology}, volume = {54}, number = {6}, pages = {690-699}, doi = {10.1080/00365521.2019.1624815}, pmid = {31190584}, issn = {1502-7708}, mesh = {Adult ; Diarrhea/etiology ; Fatty Acids, Volatile/*analysis ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Male ; Quality of Life ; RNA, Ribosomal, 16S/genetics ; Severity of Illness Index ; Young Adult ; }, abstract = {Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids). Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography. Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported. Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks. ClinicalTrials.gov ID: NCT03333291.}, }
@article {pmid31184735, year = {2019}, author = {Costello, SP and Conlon, MA and Andrews, JM}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis-Reply.}, journal = {JAMA}, volume = {321}, number = {22}, pages = {2240-2241}, doi = {10.1001/jama.2019.3950}, pmid = {31184735}, issn = {1538-3598}, mesh = {*Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid31184729, year = {2019}, author = {Benech, N and Kapel, N and Sokol, H}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis.}, journal = {JAMA}, volume = {321}, number = {22}, pages = {2240}, doi = {10.1001/jama.2019.3946}, pmid = {31184729}, issn = {1538-3598}, mesh = {*Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid31183574, year = {2019}, author = {Smibert, O and Satlin, MJ and Nellore, A and Peleg, AY}, title = {Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplantation: Management Principles.}, journal = {Current infectious disease reports}, volume = {21}, number = {7}, pages = {26}, pmid = {31183574}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a worldwide problem. Given their degree of immunosuppression and the level of contact with the healthcare system, solid organ transplant (SOT) recipients are at a disproportionately higher risk of acquisition, colonization, and infection with CRE, and outcomes from infection tend to be worse compared to non-transplant patients. Therapeutic options are limited for CRE infections although several newer agents have recently been approved for use. How well these agents perform in the setting of immunosuppression and SOT is unclear. We sought to review the epidemiology of CRE in SOT and the management principles.<br><br>RECENT FINDINGS: CRE infections are becoming an increasing problem in SOT, and donor-derived infections present a challenge in the peri-transplant period. Newer treatments for CRE are emerging that are less toxic and potentially more effective than prior CRE-active agents, but supportive clinical data are limited. Newer beta-lactamase inhibitors have good activity against KPC carbapenemases, but they lack activity against metallo-beta-lactamases (e.g., NDM). Promising data is emerging with newer agents that have activity against most carbapenemases, but, again, clinical data is needed. Combination therapy in addition to optimal pharmacokinetic and pharmacodynamics may go some way to improve outcomes against these difficult-to-treat organisms. Other novel therapies that prevent the emergence of resistance (oral beta-lactamase inhibitors) and eradication of resistant Gram-negative colonization (fecal microbiota transplant) may eventually become part of a bundle approach to reduce CRE infections in the future. As in non-transplant patients, CRE infections in the transplant setting are challenging to treat and prevent. Infection prevention and control remains crucial to prevent widespread dissemination, and unique challenges exist with donor-derived CRE and how best to manage recipients in the peri-transplant period. Newer treatments are now in early-phase clinical studies, and in vitro activity data are supportive for several agents providing hope for improved outcomes with these typically difficult-to-treat and highly morbid infections in transplant recipients.}, }
@article {pmid31178906, year = {2019}, author = {Lam, WC and Zhao, C and Ma, WJ and Yao, L}, title = {The Clinical and Steroid-Free Remission of Fecal Microbiota Transplantation to Patients with Ulcerative Colitis: A Meta-Analysis.}, journal = {Gastroenterology research and practice}, volume = {2019}, number = {}, pages = {1287493}, pmid = {31178906}, issn = {1687-6121}, abstract = {BACKGROUND AND PURPOSE: Since the first case of fecal microbiota transplantation for the treatment of ulcerative colitis was described in the year 1989, there have been an increment of case reports, case series, cohort studies, and randomized controlled trials (RCTs). In this study, we were going to investigate general clinical remission, clinical response, and steroid-free remission of fecal microbiota transplantation.<br><br>METHODS: We searched Ovid Medline, Ovid EMBASE, and Cochrane Library, focusing prospective studies including randomized controlled trials and cohort studies. The outcomes were clinical remission, clinical response, steroid-free remission, and serious adverse events. We used RevMan 5.3 software for meta-analyses.<br><br>KEY RESULTS: A total of 4 RCTs and 2 cohort studies (340 cases from 5 countries) were included. We found that FMT might be more effective than placebo on clinical remission (OR, 3.85 [2.21, 6.7]; P < 0.001; I [2] = 0%) and clinical response (OR, 2.75 [1.33, 5.67]; P = 0.006; I [2] = 49%), but no statistical difference on steroid-free remission (OR, 2.08 [0.41, 10.5]; P = 0.37; I [2] = 69%) and serious adverse events (OR, 2.0 [0.17, 22.97]; P = 0.44; I [2] = 0%).<br><br>CONCLUSIONS AND INFERENCES: Fecal microbiota transplantations were associated with significant clinical remission and response in ulcerative colitis patients while there was no significant difference found between FMT and placebo in steroid-free remission. Moreover, a common consensus on the route, volume, timing, preferred donor characteristics, and frequency of fecal administration is necessary to achieve remission.}, }
@article {pmid31178437, year = {2019}, author = {Lui, RN and Wong, SH and Lau, LHS and Chan, TT and Cheung, KCY and Li, A and Chin, ML and Tang, W and Ching, JYL and Lam, KLY and Chan, PKS and Wu, JCY and Sung, JJY and Chan, FKL and Ng, SC}, title = {Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.}, journal = {Hong Kong medical journal = Xianggang yi xue za zhi}, volume = {25}, number = {3}, pages = {178-182}, doi = {10.12809/hkmj197855}, pmid = {31178437}, issn = {1024-2708}, mesh = {Aged ; Clostridium Infections/*therapy ; Colonoscopy ; Diarrhea/*therapy ; Endoscopy, Digestive System ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Hong Kong ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong.<br><br>METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected.<br><br>RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported.<br><br>CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.}, }
@article {pmid31173991, year = {2019}, author = {Borody, TJ and Eslick, GD and Clancy, RL}, title = {Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer.}, journal = {Current opinion in pharmacology}, volume = {49}, number = {}, pages = {43-51}, doi = {10.1016/j.coph.2019.04.017}, pmid = {31173991}, issn = {1471-4973}, mesh = {Clostridioides difficile ; Clostridium Infections/*therapy ; Colorectal Neoplasms/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*therapy ; Irritable Bowel Syndrome/*therapy ; }, abstract = {Fecal microbiota transplantation (FMT) represents the most effective means of therapeutically manipulating the gastrointestinal microbiome. Originally employed as a treatment of last-resort in patients with life-threatening Clostridioides difficile infection (CDI), FMT gained widespread acceptance during the CDI epidemic, where it achieved resolution rates approaching 100%. Following our newfound appreciation for the role of the gut microbiome in both health and disease and owing to FMT's unique mechanism/s of action, FMT is rapidly advancing as an effective treatment for a number of conditions in which the gastrointestinal microbiome is thought to play a role. We review the role of FMT from its beginnings in CDI to its expansion into inflammatory bowel disease, irritable bowel syndrome, and colon cancer.}, }
@article {pmid31172380, year = {2019}, author = {Lowe, DM and Smith, PJ and Moreira, F and Workman, S and Braggins, H and Koukias, N and Buckland, MS and Wylie, P and Taylor, SA and Murray, CD}, title = {Chronic Granulomatous Disorder-Associated Colitis Can Be Accurately Evaluated with MRI Scans and Fecal Calprotectin Level.}, journal = {Journal of clinical immunology}, volume = {39}, number = {5}, pages = {494-504}, pmid = {31172380}, issn = {1573-2592}, support = {G0902022/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Colitis/blood/*diagnosis/etiology ; Colonoscopy ; Cytokines/blood ; Feces/*chemistry ; Female ; Granulomatous Disease, Chronic/blood/complications/*diagnosis ; Humans ; Leukocyte L1 Antigen Complex/*analysis ; Magnetic Resonance Imaging ; Male ; Young Adult ; }, abstract = {PURPOSE: Colitis is a common and serious complication of chronic granulomatous disorder (CGD) and requires assessment. Colonoscopy is invasive and carries risks of serious complication. We therefore assessed non-invasive monitoring via magnetic resonance imaging (MRI). We also evaluated fecal calprotectin (FCP), the Harvey-Bradshaw index (HBI) clinical score, and serum cytokines.<br><br>METHODS: We recruited 10 patients with CGD (8 males, mean age 29.6&#xa0;years), scored a modified HBI, and obtained stool for FCP. The following day we took blood for cytokine measurement via Luminex, performed MR enterography (scored by two independent radiologists using three systems: London score, CDMI, and MaRIA) followed by colonoscopy with disease activity measurement via ulcerative colitis endoscopic index of severity (UCEIS). We assessed patient experience after each investigation and overall preference with follow-up questionnaires.<br><br>RESULTS: MRI scores correlated well with colonoscopic gold standard (for London score R[2] 0.91, p&#x2009;<&#x2009;0.0001; for CDMI R[2] 0.83, p&#x2009;=&#x2009;0.0006; for MaRIA R[2] 0.89, p&#x2009;=&#x2009;0.0002). MRI was better tolerated and generally preferred, quicker, and visualized the entire large bowel whereas colonoscopy did not reach the terminal ileum in 3 participants. Elevated FCP accurately differentiated patients with colitis from those without, and log(calprotectin) correlated well with disease activity (R[2] 0.71, p&#x2009;=&#x2009;0.009). Serum interleukin (IL)-12 concentration correlated with colitis activity but IL-1&#x3b2; and TNF did not. Harvey-Bradshaw index did not correlate with colitis activity.<br><br>CONCLUSIONS: MRI and fecal calprotectin are useful methods for monitoring CGD colitis and should reduce the need for colonoscopy in these patients. IL-12 may represent an appropriate target for treatment.}, }
@article {pmid31172007, year = {2019}, author = {Herfarth, H and Barnes, EL and Long, MD and Isaacs, KL and Leith, T and Silverstein, M and Gerardin, Y and Kassam, Z}, title = {Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment.}, journal = {Inflammatory intestinal diseases}, volume = {4}, number = {1}, pages = {1-6}, pmid = {31172007}, issn = {2296-9365}, abstract = {BACKGROUND AND OBJECTIVE: A significant number of pouch patients develop antibiotic-dependent pouchitis (ADP). Microbial dysbiosis is thought to be a major driver of clinical symptoms in ADP. The objective of this proof of concept study was to evaluate safety, efficacy, and donor microbial engraftment of an intensified fecal microbiota transplant (FMT) consisting of a single endoscopic FMT followed by daily oral FMT for 2 weeks in patients with ADP.<br><br>METHODS: We performed a prospective placebo-controlled double-blind FMT trial in patents with established ADP and planned to enroll 20 patients in this proof of concept study. In case of non-response, patients were offered an optional open label active FMT treatment. The endpoints were safety, clinical remission without need for antibiotics during 16 weeks of follow-up, quantitative changes of fecal calprotectin (FCP), and engraftment of donor FMT as determined by metagenomic sequencing of the V4 region of the 16S rRNA gene.<br><br>RESULTS: Due to a lower than expected clinical remission rate and low FMT engraftment, enrollment in the study was stopped prematurely after 6 patients were included. All 6 patients enrolled in the placebo-controlled portion failed to respond and needed antibiotic rescue therapy shortly after FMT. FCP increased in the majority of patients in the setting of relapse after FMT. In the active open label FMT extension study 1 out of 5 patients achieved antibiotic-free clinical remission. FMT engraftment after active FMT was observed only in this single patient, whereas engraftment of donor FMT occurred in none of the other patients receiving active FMT, paralleling the lack of clinical response.<br><br>CONCLUSIONS: Low donor FMT engraftment resulted in low clinical efficacy of FMT in patients with ADP. Before embarking on larger clinical trials with FMT in patients with ADP or other forms of pouchitis, it is mandatory to explore approaches for superior FMT engraftment.}, }
@article {pmid31171823, year = {2019}, author = {Martínez, N and Hidalgo-Cantabrana, C and Delgado, S and Margolles, A and Sánchez, B}, title = {Filling the gap between collection, transport and storage of the human gut microbiota.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {8327}, pmid = {31171823}, issn = {2045-2322}, mesh = {Adult ; Akkermansia ; Anaerobiosis ; Bacteria/*isolation &amp; purification ; Clostridiales/isolation &amp; purification ; Faecalibacterium prausnitzii/isolation &amp; purification ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Oxygen/metabolism ; RNA, Ribosomal, 16S/genetics ; Specimen Handling/*methods ; Verrucomicrobia/isolation &amp; purification ; }, abstract = {Stool collection devices minimizing the exposure of gut bacteria to oxygen are critical for the standardization of further microbiota-based studies, analysis and developments. The aim of this work was to evidence that keeping anaerobiosis has a deep impact on the viability and diversity of the fecal microbiota that is recovered in the laboratory. Recovering certain microbial populations, such as obligate anaerobic bacteria, is particularly critical if the purpose of the study is to envisage personalized therapeutic purposes, such as autologous Fecal Microbiota Transplant. In this study the same fecal specimens were sampled in conventional stool containers and GutAlive, a disposable device that minimizes exposure of the gut microbiota to oxygen. Samples from five healthy donors were analysed and 150 differential colonies were recovered and identified by 16S rRNA gene sequencing. Globally, GutAlive maintained extremely oxygen sensitive (EOS) populations that were lost in conventional stool containers, and thus viability of species such as as Akkermansia muciniphila, Faecalibacterium prausnitzii and a novel member of the Clostridiales order was kept. These obligate anaerobes were not recovered using the conventional stool collection device. In conclusion, the use of GutAlive for stool collection and transport optimized the viability and recovery of EOS bacteria in the lab by diminishing oxygen toxicity.}, }
@article {pmid31169660, year = {2019}, author = {Kuijper, EJ and Coia, JE and Vehreschild, MJGT and Keller, J and Terveer, L}, title = {Treatment of (recurrent) Clostridioides difficile Infections in Children and Adults.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {69}, number = {2}, pages = {e57-e58}, doi = {10.1097/MPG.0000000000002387}, pmid = {31169660}, issn = {1536-4801}, mesh = {Child ; *Clostridioides difficile ; *Clostridium Infections ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; *Gastroenterology ; Humans ; United States ; }, }
@article {pmid31169659, year = {2019}, author = {Kociolek, LK and Davidovics, ZH and Kahn, SA and Kellermayer, R}, title = {Response to: Treatment of (Recurrent) Clostridioides difficile Infections in Children and Adults.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {69}, number = {2}, pages = {e58-e59}, doi = {10.1097/MPG.0000000000002388}, pmid = {31169659}, issn = {1536-4801}, mesh = {Child ; *Clostridioides difficile ; *Clostridium Infections ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; *Gastroenterology ; Humans ; United States ; }, }
@article {pmid31169545, year = {2019}, author = {Gurram, B and Sue, PK}, title = {Fecal microbiota transplantation in children: current concepts.}, journal = {Current opinion in pediatrics}, volume = {31}, number = {5}, pages = {623-629}, doi = {10.1097/MOP.0000000000000787}, pmid = {31169545}, issn = {1531-698X}, mesh = {Child ; *Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Administration of fecal material into the gastrointestinal tract, termed fecal microbiota transplantation (FMT), is increasingly recognized as an effective treatment option for recurrent Clostridium difficile infection (RCDI). The impact of FMT on host microbial communities and subsequent disease states has also been explored in recent years for conditions as varied as inflammatory bowel disease especially ulcerative colitis, metabolic diseases, such as diabetes, graft-versus-host disease in hematopoietic stem cell transplant recipients, and autism and autism spectrum disorders. The purpose of this article is to review the evidence for FMT as a treatment option in various pediatric illnesses.<br><br>RECENT FINDINGS: The rate of C. difficile infection is rising among children, and is associated with significant morbidity and disease, with recurrence in up to 20% of pediatric patients. Several randomized controlled trials evaluating the utility of FMT in RCDI in comparison to vancomycin have been published and demonstrate high rates of efficacy between 70 and 100%. In addition, the safety of FMT in the treatment of RCDI has been well described in the adult population, with several pediatric case series demonstrating similar rates of tolerability and adverse events. FMT in ulcerative colitis appears promising, especially with multiple infusions administered via the lower gastrointestinal tract. However, there are several limitations, including the lack of uniformity of protocols used, source of FMT, route of administration and the lack of standardization of concomitant therapies. The data on usage of FMT for other indications are preliminary and limited.<br><br>SUMMARY: FMT is recognized as an effective treatment option for RCDI and is increasing sought by parents. Although limited, pediatric studies to date on the use of FMT for RCDI demonstrate similar efficacy rates as in the adult population. FMT has been proposed as a treatment option for an increasing number of pediatric conditions, and additional studies are needed to delineate the efficacy of FMT outside of RCDI, as well as its short and long-term impacts on human health.}, }
@article {pmid31167808, year = {2019}, author = {}, title = {New guidelines for providing faecal microbiota transplant.}, journal = {Drug and therapeutics bulletin}, volume = {57}, number = {7}, pages = {100}, doi = {10.1136/dtb.2019.000039}, pmid = {31167808}, issn = {1755-5248}, }
@article {pmid31167080, year = {2019}, author = {Duan, Y and Zhong, Y and Xiao, H and Zheng, C and Song, B and Wang, W and Guo, Q and Li, Y and Han, H and Gao, J and Xu, K and Li, T and Yin, Y and Li, F and Yin, J and Kong, X}, title = {Gut microbiota mediates the protective effects of dietary β-hydroxy-β-methylbutyrate (HMB) against obesity induced by high-fat diets.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {9}, pages = {10019-10033}, doi = {10.1096/fj.201900665RR}, pmid = {31167080}, issn = {1530-6860}, mesh = {Adipose Tissue/drug effects/metabolism ; Adipose Tissue, Brown/metabolism ; Animals ; Bacteroidetes/isolation &amp; purification ; Diet, High-Fat/*adverse effects ; Dysbiosis/etiology/*metabolism/microbiology ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Firmicutes/isolation &amp; purification ; Gastrointestinal Microbiome/*physiology ; Gene Expression Profiling ; Insulin Resistance ; Lipid Metabolism/genetics ; Male ; Mice ; Mice, Inbred ICR ; Obesity/etiology/microbiology/*prevention &amp; control ; Propionates/metabolism/pharmacology ; RNA, Messenger/biosynthesis ; Random Allocation ; Valerates/*pharmacology/therapeutic use ; }, abstract = {Obesity increases the risk of developing insulin resistance and diabetes and is a major public health concern. Our previous study shows that dietary β-hydroxy-β-methylbutyrate (HMB) improves lipid metabolism in a pig model. However, it remains unclear whether HMB blocks obesity through gut microbiota. In this study, we found that HMB reduced body weight, alleviated the whitening of brown adipose tissue, and improved insulin resistance in mice fed a high-fat diet (HFD). High-throughput pyrosequencing of the 16S rRNA demonstrated that HMB administration significantly reversed the gut microbiota dysbiosis in HFD-fed mice, including the diversity of gut microbiota and relative abundances of Bacteroidetes and Firmicutes. Moreover, microbiota transplantation from HMB-treated mice attenuated HFD-induced lipid metabolic disorders. Furthermore, HFD-fed mice showed lower short-chain fatty acids, whereas administration of HMB increased the propionic acid production. Correlation analysis identified a significant correlation between propionic acid production and the relative Bacteroidetes abundance. Sodium propionate treatment also attenuated HFD-induced lipid metabolic disorders. Collectively, our results indicated that HMB might be used as a probiotic agent to reverse HFD-induced obesity, and the potential mechanism was associated with reprogramming gut microbiota and metabolism, especially Bacteroidetes-mediated propionic acid production. In future studies, more efforts should be made to confirm and expand the beneficial effects of HMB to human models.-Duan, Y., Zhong, Y., Xiao, H., Zheng, C., Song, B., Wang, W., Guo, Q., Li, Y., Han, H., Gao, J., Xu, K., Li, T., Yin, Y., Li, F., Yin, J., Kong, X. Gut microbiota mediates the protective effects of dietary β-hydroxy-β-methylbutyrate (HMB) against obesity induced by high-fat diets.}, }
@article {pmid31165961, year = {2019}, author = {Lee, CH and Chai, J and Hammond, K and Jeon, SR and Patel, Y and Goldeh, C and Kim, P}, title = {Long-term durability and safety of fecal microbiota transplantation for recurrent or refractory Clostridioides difficile infection with or without antibiotic exposure.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {38}, number = {9}, pages = {1731-1735}, pmid = {31165961}, issn = {1435-4373}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile ; Clostridium Infections/*drug therapy/*therapy ; Enema ; Fecal Microbiota Transplantation/methods/*standards ; Feces/microbiology ; Female ; Follow-Up Studies ; Humans ; Male ; *Microbiota ; Middle Aged ; Probiotics/therapeutic use ; Recurrence ; Surveys and Questionnaires ; Tertiary Care Centers ; Treatment Outcome ; }, abstract = {Fecal microbiota transplant (FMT) is a safe and effective treatment for recurrent or refractory Clostridioides (Clostridium) difficile infection (RCDI) in the short term. However, there are a paucity of data on long-term durability and safety of FMT. The aim of this study is to determine the long-term efficacy and safety of FMT for RCDI. Ninety-four patients underwent FMT via retention enema for RCDI between 2008 and 2012 and completed a follow-up questionnaire 4 to 8 years following the last FMT. Of these, 32 were unreachable and 37 were deceased; 23 of the remaining 25 participants completed the survey. No CDI recurrences were reported in patients treated with FMT; 12 of the 23 participants (52.2%) received at least one course of non-CDI antibiotic(s). Nine participants (40.9%) received probiotics and 4 (17.4%) received both non-CDI antibiotics and probiotics. All 23 participants rated their overall health compared with pre-FMT. Current health was considered "much better" in 17 patients (73.9%); "somewhat better" in 3 patients (13.0%); and "about the same" in 3 patients (13.0%). A total of 11 participants (47.8%) reported an increase in weight of more than 5 kg (kg) post-FMT and 9 participants (39.1%) reported no change in weight (± 5 kg). Four of the 23 participants (17.4%) reported improvement or resolution (undifferentiated colitis, n = 1; Crohn's disease, n = 2; ulcerative colitis, n = 1) of pre-existing gastrointestinal condition following FMT. Eight of 23 participants (34.8%) experienced new medical condition(s) post-FMT. The long-term efficacy (48-96 months) of FMT for RCDI appears to be durable even after non-CDI antibiotic use. Thirty percent had improvement of their pre-existing medical conditions following FMT; 73.9% reported "much better" overall health following FMT.}, }
@article {pmid31164642, year = {2019}, author = {Stebegg, M and Silva-Cayetano, A and Innocentin, S and Jenkins, TP and Cantacessi, C and Gilbert, C and Linterman, MA}, title = {Heterochronic faecal transplantation boosts gut germinal centres in aged mice.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {2443}, pmid = {31164642}, issn = {2041-1723}, support = {BBS/E/B/000C0407/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aging/*immunology ; Animals ; Cholera Toxin/immunology ; Dysbiosis/*immunology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Germinal Center/*immunology ; Immunization ; Immunoglobulin A/immunology ; Mice ; Nitrophenols/immunology ; Peyer's Patches/*immunology ; Phenylacetates/immunology ; }, abstract = {Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system; however, it is not clear whether there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer's patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli.}, }
@article {pmid31160271, year = {2019}, author = {Morffy Smith, CD and Gong, M and Andrew, AK and Russ, BN and Ge, Y and Zadeh, M and Cooper, CA and Mohamadzadeh, M and Moore, JM}, title = {Composition of the gut microbiota transcends genetic determinants of malaria infection severity and influences pregnancy outcome.}, journal = {EBioMedicine}, volume = {44}, number = {}, pages = {639-655}, pmid = {31160271}, issn = {2352-3964}, support = {R01 DK109560/DK/NIDDK NIH HHS/United States ; R01 HD046860/HD/NICHD NIH HHS/United States ; R21 AI111242/AI/NIAID NIH HHS/United States ; T32 AI060546/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Antimalarials/therapeutic use ; Combined Modality Therapy ; Cytokines/metabolism ; Disease Models, Animal ; *Disease Susceptibility ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome/drug effects ; *Genetic Predisposition to Disease ; Humans ; Malaria/*diagnosis/*etiology/therapy ; Mice ; Placenta/drug effects/parasitology/pathology ; Pregnancy ; *Pregnancy Complications, Parasitic ; Pregnancy Outcome ; Prognosis ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {BACKGROUND: Malaria infection in pregnancy is a major cause of maternal and foetal morbidity and mortality worldwide. Mouse models for gestational malaria allow for the exploration of the mechanisms linking maternal malaria infection and poor pregnancy outcomes in a tractable model system. The composition of the gut microbiota has been shown to influence susceptibility to malaria infection in inbred virgin mice. In this study, we explore the ability of the gut microbiota to modulate malaria infection severity in pregnant outbred Swiss Webster mice.<br><br>METHODS: In Swiss Webster mice, the composition of the gut microbiota was altered by disrupting the native gut microbes through broad-spectrum antibiotic treatment, followed by the administration of a faecal microbiota transplant derived from mice possessing gut microbes reported previously to confer susceptibility or resistance to malaria. Female mice were infected with P. chabaudi chabaudi AS in early gestation, and the progression of infection and pregnancy were tracked throughout gestation. To assess the impact of maternal infection on foetal outcomes, dams were sacrificed at term to assess foetal size and viability. Alternatively, pups were delivered by caesarean section and fostered to assess neonatal survival and pre-weaning growth in the absence of maternal morbidity. A group of dams was also euthanized at mid-gestation to assess infection and pregnancy outcomes.<br><br>FINDINGS: Susceptibility to infection varied significantly as a function of source of transplanted gut microbes. Parasite burden was negatively correlated with the abundance of five specific OTUs, including Akkermansia muciniphila and OTUs classified as Allobaculum, Lactobacillus, and S24-7 species. Reduced parasite burden was associated with reduced maternal morbidity and improved pregnancy outcomes. Pups produced by dams with high parasite burdens displayed a significant reduction in survival in the first days of life relative to those from malaria-resistant dams when placed with foster dams. At midgestation, plasma cytokine levels were similar across all groups, but expression of IFN&#x3b3; in the conceptus was elevated in infected dams, and IL-10 only in susceptible dams. In the latter, transcriptional and microscopic evidence of monocytic infiltration was observed with high density infection; likewise, accumulation of malaria haemozoin was enhanced in this group. These responses, combined with reduced vascularization of the placenta in this group, may contribute to poor pregnancy outcomes. Thus, high maternal parasite burden and associated maternal responses, potentially dictated by the gut microbial community, negatively impacts term foetal health and survival in the early postnatal period.<br><br>INTERPRETATION: The composition of the gut microbiota in Plasmodium chabaudi chabaudi AS-infected pregnant Swiss Webster mice transcends the outbred genetics of the Swiss Webster mouse stock as a determinant of malaria infection severity, subsequently influencing pregnancy outcomes in malaria-exposed progeny. FUND: Research reported in this manuscript was supported by the University of Florida College of Veterinary Medicine (JMM, MM, and MG), the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under award numbers T32AI060546 (to CDMS), R01HD46860 and R21AI111242 (to JMM), and R01 DK109560 (to MM). MG was supported by Department of Infectious Diseases and Immunology and University of Florida graduate assistantships. AA was supported by the 2017-2019 Peach State LSAMP Bridge to the Doctorate Program at the University of Georgia (National Science Foundation, Award # 1702361). The content is solely the responsibility of the authors and does not necessarily represent official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, or the National Institutes of Health.}, }
@article {pmid31160058, year = {2019}, author = {Nicastro, E and Di Giorgio, A and Marchetti, D and Barboni, C and Cereda, A and Iascone, M and D'Antiga, L}, title = {Diagnostic Yield of an Algorithm for Neonatal and Infantile Cholestasis Integrating Next-Generation Sequencing.}, journal = {The Journal of pediatrics}, volume = {211}, number = {}, pages = {54-62.e4}, doi = {10.1016/j.jpeds.2019.04.016}, pmid = {31160058}, issn = {1097-6833}, mesh = {ATP Binding Cassette Transporter, Subfamily B/deficiency/genetics ; Alagille Syndrome/diagnosis/genetics ; Algorithms ; Biliary Atresia/diagnosis/genetics ; Child ; Child, Preschool ; Cholestasis/*diagnosis/*genetics ; Cholestasis, Intrahepatic/diagnosis/genetics ; Exome ; Feces ; Female ; Genetic Testing ; *High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Infant, Newborn ; Male ; Phenotype ; Prospective Studies ; Tertiary Healthcare ; alpha 1-Antitrypsin Deficiency/diagnosis/genetics ; }, abstract = {OBJECTIVE: To evaluate the performance of a diagnostic protocol for neonatal/infantile cholestasis in which the main clinical patterns steered the early use of different genetic testing strategies.<br><br>STUDY DESIGN: An observational study was conducted between 2012 and 2017 in a tertiary care setting on a prospective cohort of children with cholestasis occurring at &#x2264;1&#xa0;year of age and persisting &#x2265;6&#xa0;weeks, to measure the detection rate of underlying monogenic diseases. After the exclusion of biliary atresia, a clinically driven genetic testing was performed, entailing 3 different approaches with different wideness: confirmatory single-gene testing; focused virtual panels; and wide search through trio whole-exome sequencing.<br><br>RESULTS: We enrolled 125 children (66 female, median age 2&#xa0;months); 96 (77%) patients had hypocholic stools and were evaluated rapidly to exclude biliary atresia, which was the final diagnosis in 74 (59%). Overall, 50 patients underwent genetic testing, 6 with single confirmatory gene testing, 38 through panels, and 6 with trio whole-exome sequencing because of complex phenotype. The genetic testing detection rate was 60%: the final diagnosis was Alagille syndrome in 11, progressive familial intrahepatic cholestasis type 2 in 6, alpha-1-antitrypsin deficiency in 3, and progressive familial intrahepatic cholestasis type 3 in 2; a further 7 genetic conditions were identified in 1 child each. Overall, only 18 of 125 (14%) remained with an indeterminate etiology.<br><br>CONCLUSIONS: This protocol combining clinical and genetic assessment proved to be an effective diagnostic tool for neonatal/infantile cholestasis, identifying inherited disorders with a high detection rate. It also could allow a noninvasive diagnosis in children presenting with colored stools.}, }
@article {pmid31154727, year = {2019}, author = {Yin, GF and Li, B and Fan, XM}, title = {[Effects and mechanism of fecal transplantation on acute lung injury induced by lipopolysaccharide in rats].}, journal = {Zhonghua yi xue za zhi}, volume = {99}, number = {20}, pages = {1582-1587}, doi = {10.3760/cma.j.issn.0376-2491.2019.20.013}, pmid = {31154727}, issn = {0376-2491}, mesh = {*Acute Lung Injury ; Animals ; *Fecal Microbiota Transplantation ; Lipopolysaccharides ; Lung ; NF-kappa B ; Phosphatidylinositol 3-Kinases ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; }, abstract = {Objective: To investigate the effect of fecal microbiota transplantation (FMT) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its regulatory mechanism. Methods: Fifteen rats were divided into control group, LPS group and LPS+FMT group by random number table method. LPS group and LPS+FMT group were intraperitoneally injected with LPS to generate rat ALI model. After 24 h of modeling, feces (10 ml/kg) were given to the LPS+FMT group twice a day, and the control group and LPS group were given the same amount of normal saline. The intervention lasted for 2 days. After 24 h of the last fecal microbiota transplantation, arterial blood gas analysis was performed in each group. Then rats were sacrificed and enzyme-linked immunosorbent (ELISA) method was used to detect intercellular adhesion molecule 1 (ICAM-1) content in the serum and bronchoalveolar lavage fluid (BALF). The lung wet-dry weight ratio (W/D) was evaluated; HE staining and lung tissue pathology scoring, immunohistochemical detection of nuclear factor-kappa B (NF-κB) predominate nuclear expression and expression of ICAM-1 of alveolar epithelial cells were conducted; Western blot was used to detect the expression of proteins related to the intracellular phosphatidylinositol kinase (PI3K)/protein kinase (AKT) signaling pathway. Samples of rat feces were collected and DNA was extracted. Polymerase chain reaction (PCR) products of the V3 and V4 regions of the 16S ribosomal RNA gene (16SrDNA) were sequenced at high throughput, and bioinformatics analysis was conducted on the microbial community based on the operational classification unit. Results: The lung W/D and lung histopathological score of the LPS group were significantly higher than those of the control group, while the arterial partial oxygen pressure (PaO(2)) of the LPS group was significantly lower than that of the control group [(79.2±5.89 vs 95.2±2.77) mmHg, 1 mmHg=0.133 kPa](all P<0.05). The results of intestinal flora sequencing revealed that the diversity index of LPS group was significantly higher than that of the control group, while the lactobacillus of LPS group rats was significantly lower than that of the control group. The content of ICAM-1 in serum, BALF and its relative expression on the cell membrane in the LPS group was significantly higher than that in the control group [(8.64±0.87) vs (7.40±0.32) ng/L; (0.941±0.035) vs (0.739±0.079) ng/L; (0.250±0.010) vs (0.076±0.010)] (all P<0.05). Moreover, the relative expression levels of phosphorylated P65 (p-P65), p-PI3K and p-AKT nucleoprotein in the LPS group were significantly higher than those in the control group (4.89±0.27 vs 3.28±0.13, 0.265±0.030 vs 0.036±0.013 and 0.444±0.040 vs 0.109±0.016) (all P<0.05). The above injury effect was reduced after fecal fungus transplantation. The lung W/D and lung pathological score of LPS+FMT group were significantly lower than those of LPS group, and PaO(2) of LPS+FMT group was significantly higher than that of LPS group [(88.0±3.53) mmHg]. The results of intestinal flora sequencing revealed that the diversity index of LPS+FMT group was significantly lower than that of LPS group, and the lactobacillus genus of LPS+FMT group was significantly higher than that of LPS group. ICAM-1 in the blood serum ((7.44±0.46) ng/L), BALF (0.834±0.040) ng/L) and its relative expression on alveolar epithelial cell membrane (0.173±0.030), the relative expression of p-P65, p-PI3K and p-AKT protein of NF-κB in alveolar epithelial cells was down-regulated ((2.99±0.28, 0.090±0.013 and 0.206±0.018) in LPS+FMT group than those of LPS group, the differences were statistically significant (all P<0.05). Conclusion: Fecal transplantation can alleviate lipopolysaccharide-induced acute lung injury in rats, and its regulatory effect may be related to inhibiting the activation of PI3K/AKT/NF-κB signaling pathway and reducing the expression of inflammatory factor ICAM-1.}, }
@article {pmid31154629, year = {2019}, author = {Kim, KO and Schwartz, MA and Lin, OST and Chiorean, MV and Gluck, M}, title = {Reducing Cost and Complexity of Fecal Microbiota Transplantation Using Universal Donors for Recurrent Clostridium difficile Infection.}, journal = {Advances in therapy}, volume = {36}, number = {8}, pages = {2052-2061}, pmid = {31154629}, issn = {1865-8652}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*economics/*methods ; Feces/*microbiology ; Female ; Humans ; Living Donors/*statistics &amp; numerical data ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Secondary Prevention/*economics/*methods ; Treatment Outcome ; Young Adult ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation resolves recurrent Clostridium difficile infections in greater than 82% of patients. Highly screened, processed universal donor fecal material is available. We compared cost and scheduling efficiency of fecal microbiota transplantation by universal donors to patient-directed donors.<br><br>METHODS: Medical records from a prospectively maintained database of recurrent C.&#xa0;difficile patients who underwent fecal microbiota transplantation between 2012 and 2017 were reviewed retrospectively. Patient-directed donor stool was prepared in our microbiology laboratory using protocol-based screening. We transitioned to purchasing and using universal donor fecal material in 2015. Clinical outcomes, adverse events, time between consult to infusion, consultation fees, and material costs were compared. This was a retrospective comparison of two historical cohorts.<br><br>RESULTS: A total of 111 fecal microbiota transplantations were performed on 105 patients (56 from patient-directed donors and 55 from universal donors). Median recipient age was 66&#xa0;years (18-96) with male to female ratio of 1:2.7, equivalent in both cohorts. Total consultation fees were significantly lower in the universal donor group owing to fewer infectious disease consultations. Costs for donor screening and stool preparation were lower in the universal donor cohort ($485.0 vs. $1189.90&#x2009;&#xb1;&#x2009;541.4, p&#x2009;<&#x2009;0.001, 95% CI 559.9-849.9). Time from consultations to infusion was shorter in the universal donor cohort (18.9&#x2009;&#xb1;&#x2009;19.1 vs. 36.4&#x2009;&#xb1;&#x2009;23.3&#xa0;days, p&#x2009;<&#x2009;0.001, 95% CI 9.521-25.591). Recurrences within 8&#xa0;weeks after fecal microbiota transplantation were equivalent (p&#x2009;=&#x2009;0.354). Adverse events were equivalent.<br><br>CONCLUSIONS: Fecal microbiota transplantation using universal donors versus patient-directed donors for recurrent C.&#xa0;difficile showed comparable efficacy and short-term complications. The use of universal donors resulted in significant cost savings and scheduling efficiency.}, }
@article {pmid31148601, year = {2019}, author = {Vijayvargiya, P and Gonsalves, W and Burton, D and Hogan, WJ and Miceli, T and Rossini, W and Taylor, A and Lueke, A and Donato, L and Camilleri, M}, title = {Increased fecal primary bile acids in multiple myeloma with engraftment syndrome diarrhea after stem cell transplant.}, journal = {Bone marrow transplantation}, volume = {54}, number = {11}, pages = {1898-1907}, pmid = {31148601}, issn = {1476-5365}, mesh = {Adult ; Autografts ; Bile Acids and Salts/*metabolism ; *Diarrhea/etiology/metabolism ; *Feces ; Female ; Gastrointestinal Motility ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; *Multiple Myeloma/metabolism/therapy ; Prospective Studies ; Syndrome ; }, abstract = {Autologous stem cell transplant (ASCT) for multiple myeloma (MM) is associated with diarrhea during the peri-transplant period. We aimed to appraise mechanisms of peri-ASCT diarrhea in a prospective, longitudinal study of patients with MM. We compared by repeated measures (RM)-ANOVA daily bowel movements (BMs) and consistency [7-point Bristol Stool Form Scale (BSFS)], fecal calprotectin (intestinal inflammation), [13]C-mannitol excretion in urine 0-2 h (small intestinal permeability), fasting serum C4 (bile acid synthesis) and total and primary bile acid in stool samples during baseline, peri-transplant period (Days 5-7 after stem cell infusion), and after hematological recovery post-ASCT. The 12 (5F, 7M) patients' median age was 61 y (IQR 54.8-63.3). All participants reported increased BMs (increase of 2 and 1 per day with and without engraftment syndrome, respectively). There were no significant increases in serum C4, total fecal bile acids, or intestinal permeability. Relative to patients without engraftment syndrome, four participants with engraftment syndrome had looser stool consistency (mean 2.6 points higher BSFS compared to without engraftment syndrome), increased primary fecal bile acids relative to baseline (>33 µmol/L vs. 6 µmol/L without engraftment syndrome), and increased fecal calprotectin compared to baseline (313 μg/mL vs. 35.6 μg/mL without engraftment syndrome; p = 0.06). Engraftment syndrome post-ASCT is associated with increased fecal primary bile acids.}, }
@article {pmid31147381, year = {2020}, author = {de Groot, P and Scheithauer, T and Bakker, GJ and Prodan, A and Levin, E and Khan, MT and Herrema, H and Ackermans, M and Serlie, MJM and de Brauw, M and Levels, JHM and Sales, A and Gerdes, VE and Ståhlman, M and Schimmel, AWM and Dallinga-Thie, G and Bergman, JJ and Holleman, F and Hoekstra, JBL and Groen, A and Bäckhed, F and Nieuwdorp, M}, title = {Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time.}, journal = {Gut}, volume = {69}, number = {3}, pages = {502-512}, pmid = {31147381}, issn = {1468-3288}, mesh = {Adult ; Aged ; Bile Acids and Salts/analysis ; Chemokine CCL2/blood/genetics ; Energy Metabolism ; Fatty Acids, Volatile/analysis ; *Fecal Microbiota Transplantation ; Feces/chemistry ; *Gastric Bypass ; Gastrointestinal Microbiome ; Gastrointestinal Transit ; Gene Expression ; Glucose/*metabolism ; Humans ; *Insulin Resistance ; Lipolysis ; Male ; Metabolic Syndrome/*metabolism/physiopathology/therapy ; Metabolomics ; Middle Aged ; Subcutaneous Fat/metabolism ; Tissue Donors ; Young Adult ; }, abstract = {OBJECTIVE: Bariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-naïve, obese, insulin-resistant male subjects.<br><br>DESIGN: Subjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2&#x2009;weeks after FMT by hyperinsulinaemic euglycaemic stable isotope ([2]H2-glucose and [2]H5-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks.<br><br>RESULTS: We observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 &#xb5;mol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa.<br><br>CONCLUSION: Allogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects.<br><br>TRIAL REGISTRATION NUMBER: NTR4327.}, }
@article {pmid31145641, year = {2019}, author = {Ji, J and Ge, X and Chen, Y and Zhu, B and Wu, Q and Zhang, J and Shan, J and Cheng, H and Shi, L}, title = {Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {8}, pages = {9308-9322}, doi = {10.1096/fj.201802659RR}, pmid = {31145641}, issn = {1530-6860}, mesh = {Animals ; Colitis/*chemically induced/*metabolism ; Dextran Sulfate/*toxicity ; Enzyme-Linked Immunosorbent Assay ; Female ; Gas Chromatography-Mass Spectrometry ; Gastrointestinal Microbiome/drug effects ; Intestinal Mucosa/drug effects/metabolism ; Mice ; Mice, Inbred BALB C ; Microbiota/drug effects ; T-Lymphocytes, Regulatory/*metabolism ; Th17 Cells/*metabolism ; Umbelliferones/*therapeutic use ; }, abstract = {Inflammatory bowel diseases (IBDs) are characterized by chronic pathologies associated with extensive gut dysbiosis and intestinal inflammation. Hence, endeavors to improve the inflammatory pathology by manipulating gut microbiota are ongoing. Daphnetin (DAPH) is a coumarin derivative extracted from Daphne odora var with anti-inflammatory and immune-regulatory properties that has been widely used in treating inflammatory disorders. Herein, we showed that DAPH remarkably alleviated experimental colitis by reducing colonic inflammation, improving colonic integrity, and reestablishing immune and metabolic homeostasis in the inflicted intestines. Our analysis showed that DAPH modified the composition of gut microbiota and altered the metabolic profiles in dextran sulfate sodium-treated mice. In particular, this agent significantly elevated the abundance of short-chain fatty acid (SCFA)-producing gut microbiota, causatively related with the enhanced development of Treg cells and the reduced proinflammatory Th17 cell differentiation. More critically, the protective effect of DAPH was shown to be transmissible among colitic mice through cohousing or fecal microbiota transplantation, further substantiating the importance of SCFA-producing gut microbiota in DAPH action. We thus for the first time reveal the potential of DAPH in resetting the gut microbiome and reestablishing immune homeostasis in colitic mice, which may have clinical implications for treating IBD.-Ji, J., Ge, X., Chen, Y., Zhu, B., Wu, Q., Zhang, J., Shan, J., Cheng, H., Shi, L. Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance.}, }
@article {pmid31144984, year = {2019}, author = {Tashiro, H and Cho, Y and Kasahara, DI and Brand, JD and Bry, L and Yeliseyev, V and Abu-Ali, G and Huttenhower, C and Shore, SA}, title = {Microbiota Contribute to Obesity-related Increases in the Pulmonary Response to Ozone.}, journal = {American journal of respiratory cell and molecular biology}, volume = {61}, number = {6}, pages = {702-712}, pmid = {31144984}, issn = {1535-4989}, support = {P30 ES000002/ES/NIEHS NIH HHS/United States ; R01 ES013307/ES/NIEHS NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; T32 HL007118/HL/NHLBI NIH HHS/United States ; R21 ES024032/ES/NIEHS NIH HHS/United States ; }, mesh = {Airway Resistance ; Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Asthma/etiology/therapy ; Cellulose/administration &amp; dosage ; Dietary Fiber/administration &amp; dosage ; Fecal Microbiota Transplantation ; Female ; Fermentation ; Gastrointestinal Microbiome/drug effects/*physiology ; Germ-Free Life ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/*complications/genetics/microbiology/physiopathology ; Ozone/*toxicity ; Pectins/administration &amp; dosage/therapeutic use ; Receptors, Leptin/deficiency ; Respiratory Hypersensitivity/chemically induced/diet therapy/*etiology/microbiology ; }, abstract = {Obesity is a risk factor for asthma, especially nonatopic asthma, and attenuates the efficacy of standard asthma therapeutics. Obesity also augments pulmonary responses to ozone, a nonatopic asthma trigger. The purpose of this study was to determine whether obesity-related alterations in gut microbiota contribute to these augmented responses to ozone. Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in obese db/db mice than in lean wild-type control mice. Depletion of gut microbiota with a cocktail of antibiotics attenuated obesity-related increases in the response to ozone, indicating a role for microbiota. Moreover, ozone-induced airway hyperresponsiveness was greater in germ-free mice that had been reconstituted with colonic contents of db/db than in wild-type mice. In addition, compared with dietary supplementation with the nonfermentable fiber cellulose, dietary supplementation with the fermentable fiber pectin attenuated obesity-related increases in the pulmonary response to ozone, likely by reducing ozone-induced release of IL-17A. Our data indicate a role for microbiota in obesity-related increases in the response to an asthma trigger and suggest that microbiome-based therapies such as prebiotics may provide an alternative therapeutic strategy for obese patients with asthma.}, }
@article {pmid31144383, year = {2019}, author = {Peirce, JM and Alviña, K}, title = {The role of inflammation and the gut microbiome in depression and anxiety.}, journal = {Journal of neuroscience research}, volume = {97}, number = {10}, pages = {1223-1241}, doi = {10.1002/jnr.24476}, pmid = {31144383}, issn = {1097-4547}, mesh = {Animals ; *Anxiety ; *Depression ; *Gastrointestinal Microbiome ; Humans ; *Inflammation ; Stress, Psychological ; }, abstract = {The study of the gut microbiome has increasingly revealed an important role in modulating brain function and mental health. In this review, we underscore specific pathways and mechanisms by which the gut microbiome can promote the development of mental disorders such as depression and anxiety. First, we review the involvement of the stress response and immune system activation in the development of depression and anxiety. Then, we examine germ-free murine models used to uncover the role of the gut microbiome in developing and modulating pertinent activity in the brain and the immune system. We also document multiple pathways by which stress-induced inflammation harms brain function and ultimately affects mental health, and review how probiotic and prebiotic treatments have shown to be beneficial. Lastly, we provide an overview of gut microbiome-derived compounds (short-chain fatty acids, tryptophan catabolites, microbial pattern recognition) and related mechanisms (vagal nerve activity and fecal microbiota transplants) involved in mediating the influence of the gut microbiome to mental health. Overall, a picture of the gut microbiome playing a facilitating role between stress response, inflammation, and depression, and anxiety is emerging. Future research is needed to firmly establish the microbiome's causal role, to further elucidate the mechanisms by which gut microbes influence brain function and mental health, and to possibly develop treatments that improve mental health through microbiotic targets.}, }
@article {pmid31143780, year = {2019}, author = {Zeng, W and Shen, J and Bo, T and Peng, L and Xu, H and Nasser, MI and Zhuang, Q and Zhao, M}, title = {Cutting Edge: Probiotics and Fecal Microbiota Transplantation in Immunomodulation.}, journal = {Journal of immunology research}, volume = {2019}, number = {}, pages = {1603758}, pmid = {31143780}, issn = {2314-7156}, mesh = {Animals ; Clinical Trials as Topic ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome/*immunology ; Host-Pathogen Interactions ; Humans ; Immunomodulation ; Inflammatory Bowel Diseases/*therapy ; *Probiotics ; }, abstract = {Probiotics are commensal or nonpathogenic microbes that confer beneficial effects on the host through several mechanisms such as competitive exclusion, antibacterial effects, and modulation of immune responses. Some probiotics have been found to regulate immune responses via immune regulatory mechanisms. T regulatory (Treg) cells, T helper cell balances, dendritic cells, macrophages, B cells, and natural killer (NK) cells can be considered as the most determinant dysregulated mediators in immunomodulatory status. Recently, fecal microbiota transplantation (FMT) has been defined as the transfer of distal gut microbial communities from a healthy individual to a patient's intestinal tract to cure some immune disorders (mainly inflammatory bowel diseases). The aim of this review was followed through the recent literature survey on immunomodulatory effects and mechanisms of probiotics and FMT and also efficacy and safety of probiotics and FMT in clinical trials and applications.}, }
@article {pmid31142049, year = {2019}, author = {Burrello, C and Giuffrè, MR and Macandog, AD and Diaz-Basabe, A and Cribiù, FM and Lopez, G and Borgo, F and Nezi, L and Caprioli, F and Vecchi, M and Facciotti, F}, title = {Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition.}, journal = {Cells}, volume = {8}, number = {6}, pages = {}, pmid = {31142049}, issn = {2073-4409}, mesh = {Animals ; Chronic Disease ; Cytokines/metabolism ; Dextran Sulfate ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Inflammation/chemically induced/*pathology ; Intestines/*immunology/*microbiology/pathology ; Mice ; Mice, Inbred C57BL ; Phenotype ; Principal Component Analysis ; T-Lymphocytes/*immunology ; }, abstract = {Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.}, }
@article {pmid31139852, year = {2019}, author = {Hansen, CHF and Larsen, CS and Petersson, HO and Zachariassen, LF and Vegge, A and Lauridsen, C and Kot, W and Krych, &#x141; and Nielsen, DS and Hansen, AK}, title = {Targeting gut microbiota and barrier function with prebiotics to alleviate autoimmune manifestations in NOD mice.}, journal = {Diabetologia}, volume = {62}, number = {9}, pages = {1689-1700}, pmid = {31139852}, issn = {1432-0428}, mesh = {Animals ; Autoimmunity/physiology ; Dietary Supplements ; Female ; Gastrointestinal Microbiome/drug effects/*physiology ; Glucuronates/therapeutic use ; Mice ; Mice, Inbred NOD ; Oligosaccharides/therapeutic use ; *Prebiotics ; }, abstract = {AIMS/HYPOTHESIS: Adopting a diet containing indigestible fibre compounds such as prebiotics to fuel advantageous bacteria has proven beneficial for alleviating inflammation. The effect of the microbial changes on autoimmunity, however, remains unknown. We studied the effects of prebiotic xylooligosaccharides (XOS) on pancreatic islet and salivary gland inflammation in NOD mice and tested whether these were mediated by the gut microbiota.<br><br>METHODS: Mother and offspring mice were fed an XOS-supplemented diet until diabetes onset or weaning and were compared with a control-fed group. Diabetes incidence was monitored, insulitis and sialadenitis were scored in histological sections from adult mice, and several metabolic and immune variables were analysed in mice before the development of diabetes. Gut barrier function was assessed using an in vivo FITC-dextran permeability test. The importance of XOS-mediated gut microbial changes were evaluated in antibiotic-treated mice fed either XOS or control diet or given a faecal microbiota transplant from test animals.<br><br>RESULTS: Diabetes onset was delayed in the XOS-fed mice, which also had fewer cellular infiltrations in their pancreatic islets and salivary glands. Interestingly, insulitis was most reduced in the XOS-fed groups when the mice were also treated with an antibiotic cocktail. There was no difference in sialadenitis between the dietary groups treated with antibiotics; the mice were protected by microbiota depletion regardless of diet. Faecal microbiota transplantation was not able to transfer protection. No major differences in glucose-insulin regulation, glucagon-like peptide-1, or short-chain fatty acid production were related to the XOS diet. The XOS diet did, however, reduce gut permeability markers in the small and large intestine. This was accompanied by a more anti-inflammatory environment locally and systemically, dominated by a shift from M1 to M2 macrophages, a higher abundance of activated regulatory T cells, and lower levels of induction of natural killer T cells and cytotoxic T cells.<br><br>CONCLUSIONS/INTERPRETATION: Prebiotic XOS have microbiota-dependent effects on salivary gland inflammation and microbiota-independent effects on pancreatic islet pathology that are accompanied by an improved gut barrier that seems able to heighten control of intestinal diabetogenic antigens that have the potential to penetrate the mucosa to activate autoreactive immune responses.}, }
@article {pmid31139366, year = {2019}, author = {Zingg, W and Park, BJ and Storr, J and Ahmad, R and Tarrant, C and Castro-Sanchez, E and Perencevich, E and Widmer, A and Krause, KH and Kilpatrick, C and Tomczyk, S and Allegranzi, B and Cardo, D and Pittet, D and , }, title = {Technology for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva IPC-Think Tank (Part 2).}, journal = {Antimicrobial resistance and infection control}, volume = {8}, number = {}, pages = {83}, pmid = {31139366}, issn = {2047-2994}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/*genetics ; Cross Infection/microbiology/*prevention &amp; control/transmission ; *Drug Resistance, Bacterial ; Group Processes ; Hand Hygiene ; Health Personnel ; Humans ; Infection Control/*methods ; Internationality ; Microbiota ; Switzerland ; Technology/*methods ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: The high burden of healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) is partially due to excessive antimicrobial use both in human and animal medicine worldwide. How can technology help to overcome challenges in infection prevention and control (IPC) and to prevent HAI and emerging AMR?<br><br>METHODS: In June 2017, 42 international experts convened in Geneva, Switzerland to discuss four potential domains of technology in IPC and AMR: 1) role and potential contribution of microbiome research; 2) whole genome sequencing; 3) effectiveness and benefit of antimicrobial environmental surfaces; and 4) future research in hand hygiene.<br><br>RESULTS: Research on the microbiome could expand understanding of antimicrobial use and also the role of probiotics or even faecal transplantation for therapeutic purposes. Whole genome sequencing will provide new insights in modes of transmission of infectious diseases. Although it is a powerful tool for public health epidemiology, some challenges with interpretation and costs still need to be addressed. The effectiveness and cost-effectiveness of antimicrobially coated or treated environmental high-touch surfaces requires further research before they can be recommended for routine use. Hand hygiene implementation can be advanced, where technological enhancement of surveillance, technique and compliance are&#xa0;coupled with reminders for healthcare professionals.<br><br>CONCLUSIONS: The four domains of technological innovation contribute to the prevention of HAI and AMR at different levels. Microbiome research may offer innovative concepts for future prevention, whole genome sequencing could detect new modes of transmission and become an additional tool for effective public health epidemiology, antimicrobial surfaces might help to decrease the environment as source of transmission but continue to raise more questions than answers, and technological innovation may have a role in improving surveillance approaches and supporting best practice in hand hygiene.}, }
@article {pmid31138018, year = {2020}, author = {Paik, J and Meeker, S and Hsu, CC and Seamons, A and Pershutkina, O and Snyder, JM and Brabb, T and Maggio-Price, L}, title = {Validation studies for germ-free Smad3[-/-] mice as a bio-assay to test the causative role of fecal microbiomes in IBD.}, journal = {Gut microbes}, volume = {11}, number = {1}, pages = {21-31}, pmid = {31138018}, issn = {1949-0984}, support = {K01 OD021420/OD/NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biological Assay ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Smad3 Protein/*genetics ; }, abstract = {While the association between microbiomes and inflammatory bowel disease (IBD) is well known, establishing causal relationships between the two is difficult in humans. Germ-free (GF) mice genetically susceptible to IBD can address this question. Smad3[-/-] mice with defective transforming growth factor ß signaling are a model of IBD and colon cancer. They develop IBD upon colonization with Helicobacter under specific pathogen-free conditions, suggesting a role of the microbiome in IBD in this model. Thus, we rederived Smad3[-/-] mice GF to determine the potential of using these mice for testing the causative role of microbiomes in IBD. We found that fecal microbiomes from mice with IBD cause more severe gut inflammation in GF Smad3[-/-] and wild type mice compared to microbiomes from healthy mice and that Helicobacter induces gut inflammation within the context of other microbiomes but not by itself. Unexpectedly, GF Smad3[+/+] and Smad3[+/-] mice given IBD microbiomes develop IBD despite their lack of disease in SPF conditions upon Helicobacter infection. This was not unique to the background strain of our Smad3 model (129); both wild type C57BL/6 and 129 strains developed IBD upon fecal transfer. However, wild type Swiss Webster stock was not susceptible, indicating that the genetic background of recipient mice influences the severity of IBD following fecal transfer. Our data suggest that the microbiome is an independent risk factor contributing to IBD development, and careful characterization of new GF models is needed to understand potential sources of confounding factors influencing microbiome studies in these mice.}, }
@article {pmid31136009, year = {2019}, author = {Ianiro, G and Eusebi, LH and Black, CJ and Gasbarrini, A and Cammarota, G and Ford, AC}, title = {Systematic review with meta-analysis: efficacy of faecal microbiota transplantation for the treatment of irritable bowel syndrome.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {50}, number = {3}, pages = {240-248}, doi = {10.1111/apt.15330}, pmid = {31136009}, issn = {1365-2036}, mesh = {Adult ; Colitis, Ulcerative/epidemiology/microbiology/therapy ; *Fecal Microbiota Transplantation/methods/statistics &amp; numerical data ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Humans ; Irritable Bowel Syndrome/epidemiology/microbiology/*therapy ; Randomized Controlled Trials as Topic/statistics &amp; numerical data ; Treatment Outcome ; }, abstract = {BACKGROUND: Increasing evidence supports the role of the gut microbiota in the aetiology of irritable bowel syndrome (IBS). Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridioides difficile infection in randomised controlled trials (RCTs), and may be beneficial in ulcerative colitis. However, its efficacy in IBS is uncertain.<br><br>AIM: To perform a systematic review and meta-analysis to examine this issue.<br><br>METHODS: We searched MEDLINE, EMBASE, EMBASE Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov through to March 2019. RCTs recruiting adults with IBS, which compared FMT with placebo, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% CI.<br><br>RESULTS: The search strategy identified 322 citations. Five RCTs were eligible for inclusion, containing 267 patients. Overall, 92.2% of included patients had IBS-D or IBS-M, and only 7.8% IBS-C. When data were pooled for all patients, irrespective of stool type, the RR of IBS symptoms not improving was 0.98 (95% CI 0.58-1.66). Placebo capsules administered orally were superior to capsules containing donor stool in two pooled trials (RR&#xa0;=&#xa0;1.96; 95% CI 1.19-3.20). FMT from donor stool delivered via colonoscopy was superior to autologous stool in two pooled RCTs (RR&#xa0;=&#xa0;0.63; 95% CI 0.43-0.93). FMT from donor stool via nasojejunal tube showed a trend towards a benefit over autologous stool in one trial (RR&#xa0;=&#xa0;0.69; 95% CI 0.46-1.02).<br><br>CONCLUSIONS: Fresh or frozen donor stool delivered via colonoscopy or nasojejunal tube may be beneficial in IBS. Larger, more rigorously conducted trials of FMT in IBS are needed.}, }
@article {pmid31133692, year = {2019}, author = {Aagaard, K and Hohmann, E}, title = {Regulating microbiome manipulation.}, journal = {Nature medicine}, volume = {25}, number = {6}, pages = {874-876}, pmid = {31133692}, issn = {1546-170X}, mesh = {Drug Approval/legislation &amp; jurisprudence ; Fecal Microbiota Transplantation/adverse effects ; Humans ; Legislation, Medical ; *Microbiota ; Risk Factors ; Safety/legislation &amp; jurisprudence ; United States ; United States Food and Drug Administration/legislation &amp; jurisprudence ; }, }
@article {pmid31130466, year = {2019}, author = {Chagwedera, DN and Ang, QY and Bisanz, JE and Leong, YA and Ganeshan, K and Cai, J and Patterson, AD and Turnbaugh, PJ and Chawla, A}, title = {Nutrient Sensing in CD11c Cells Alters the Gut Microbiota to Regulate Food Intake and Body Mass.}, journal = {Cell metabolism}, volume = {30}, number = {2}, pages = {364-373.e7}, pmid = {31130466}, issn = {1932-7420}, support = {R01 DK101064/DK/NIDDK NIH HHS/United States ; T32 GM007618/GM/NIGMS NIH HHS/United States ; R01 DK105175/DK/NIDDK NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; R01 DK094641/DK/NIDDK NIH HHS/United States ; F31 DK112669/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Body Weight/*physiology ; CD11 Antigens/*metabolism ; Eating/*physiology ; Gastrointestinal Microbiome/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nutrients/*metabolism ; Tuberous Sclerosis Complex 1 Protein/deficiency/immunology ; }, abstract = {Microbial dysbiosis and inflammation are implicated in diet-induced obesity and insulin resistance. However, it is not known whether crosstalk between immunity and microbiota also regulates metabolic homeostasis in healthy animals. Here, we report that genetic deletion of tuberous sclerosis 1 (Tsc1) in CD11c[+] myeloid cells (Tsc1[f/f]CD11c[Cre] mice) reduced food intake and body mass in the absence of metabolic disease. Co-housing and fecal transplant experiments revealed a dominant role for the healthy gut microbiota in regulation of body weight. 16S rRNA sequencing, selective culture, and reconstitution experiments further confirmed that selective deficiency of Lactobacillus johnsonii Q1-7 contributed to decreased food intake and body mass in Tsc1[f/f]CD11c[Cre] mice. Mechanistically, activation of mTORC1 signaling in CD11c cells regulated production of L. johnsonii Q1-7-specific IgA, allowing for its stable colonization in the gut. Together, our findings reveal an unexpected transkingdom immune-microbiota feedback loop for homeostatic regulation of food intake and body mass in mammals.}, }
@article {pmid31127327, year = {2019}, author = {Alagna, L and Haak, BW and Gori, A}, title = {Fecal microbiota transplantation in the ICU: perspectives on future implementations.}, journal = {Intensive care medicine}, volume = {45}, number = {7}, pages = {998-1001}, pmid = {31127327}, issn = {1432-1238}, mesh = {Fecal Microbiota Transplantation/*methods ; Humans ; Intensive Care Units/*organization &amp; administration ; Patient Safety ; Patient Selection ; }, }
@article {pmid31125783, year = {2019}, author = {Cavuoto, KM and Banerjee, S and Galor, A}, title = {Relationship between the microbiome and ocular health.}, journal = {The ocular surface}, volume = {17}, number = {3}, pages = {384-392}, doi = {10.1016/j.jtos.2019.05.006}, pmid = {31125783}, issn = {1937-5913}, support = {I01 CX001089/CX/CSRD VA/United States ; L30 EY019842/EY/NEI NIH HHS/United States ; }, mesh = {Eye Diseases/microbiology/*therapy ; Humans ; Microbiota/*physiology ; Probiotics/*therapeutic use ; }, abstract = {The microbiome is important to the host as a whole, both in maintenance of health and in the pathophysiology of disease. The purpose of this review is to explore the relationship between the gut, ocular microbiome, and ocular disease states. We will also discuss how the microbiome can serve as a potential target for treatment, by methods such as modulation of diet, probiotics and fecal microbiota transplantation. The information discussed in the review has been gathered using literature published from 2004 to November 2018, as indexed in PubMed.}, }
@article {pmid31124558, year = {2019}, author = {Sharpton, SR and Maraj, B and Harding-Theobald, E and Vittinghoff, E and Terrault, NA}, title = {Gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression.}, journal = {The American journal of clinical nutrition}, volume = {110}, number = {1}, pages = {139-149}, pmid = {31124558}, issn = {1938-3207}, support = {T32 DK060414/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Alanine Transaminase/blood ; Anti-Bacterial Agents/administration &amp; dosage ; Body Mass Index ; Child ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Insulin Resistance ; Liver/pathology/physiopathology ; Non-alcoholic Fatty Liver Disease/physiopathology/*therapy ; Probiotics/therapeutic use ; Randomized Controlled Trials as Topic ; Synbiotics/administration &amp; dosage ; Triglycerides/blood ; }, abstract = {BACKGROUND: Preclinical evidence suggests that modulation of the gut microbiome could represent a new therapeutic target in nonalcoholic fatty liver disease (NAFLD).<br><br>OBJECTIVES: The aim of this study was to evaluate the most current evidence for liver-specific and metabolic effects of microbiome-targeted therapies (MTTs) in persons with NAFLD.<br><br>METHODS: We searched multiple electronic databases for randomized controlled trials (RCTs) published from January 1, 2005 to December 1, 2018 that enrolled persons with NAFLD who received MTT rather than placebo or usual care. MTT was defined as antibiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT). Clinical outcomes were pooled with the use of random-effects models and heterogeneity was assessed with the I2 statistic. A random-effects meta-regression was performed to determine sources of heterogeneity in prevalence estimates between studies.<br><br>RESULTS: Twenty-one RCTs (1252 participants) were included; 9 evaluated probiotics and 12 evaluated synbiotics, with treatment duration ranging from 8 to 28 wk. No RCTs examined the efficacy of antibiotics or FMT. Probiotics/synbiotics were associated with a significant reduction in alanine aminotransferase activity [ALT, weighted mean difference (WMD): -11.23 IU/L; 95% CI: -15.02, -7.44 IU/L] and liver stiffness measurement (LSM) by elastography (reflecting inflammation and fibrosis) (WMD: -0.70 kPa; 95% CI: -1.00, -0.40 kPa), although analyses showed heterogeneity (I2&#xa0;=&#xa0;90.6% and I2&#xa0;=&#xa0;93.4%, respectively). Probiotics/synbiotics were also associated with increased odds of improvement in hepatic steatosis, as graded by ultrasound (OR: 2.40; 95% CI: 1.50, 3.84; I2&#xa0;=&#xa0;22.4%). No RCTs examined sequential liver biopsy findings. Probiotics (WMD: -1.84; 95% CI: -3.30, -0.38; I2&#xa0;=&#xa0;23.6%), but not synbiotics (WMD: -0.85; 95% CI: -2.17, 0.47; I2&#xa0;=&#xa0;96.6%), were associated with a significant reduction in body mass index.<br><br>CONCLUSIONS: The use of probiotics/synbiotics was associated with improvement in liver-specific markers of hepatic inflammation, LSM, and steatosis in persons with NAFLD. Although promising, given the heterogeneity in pooled analyses, additional well-designed RCTs are needed to define the efficacy of probiotics/synbiotics for treatment of NAFLD. This study was registered with PROSPERO as CRD42018091455.}, }
@article {pmid31124390, year = {2019}, author = {Li, N and Wang, Q and Wang, Y and Sun, A and Lin, Y and Jin, Y and Li, X}, title = {Fecal microbiota transplantation from chronic unpredictable mild stress mice donors affects anxiety-like and depression-like behavior in recipient mice via the gut microbiota-inflammation-brain axis.}, journal = {Stress (Amsterdam, Netherlands)}, volume = {22}, number = {5}, pages = {592-602}, doi = {10.1080/10253890.2019.1617267}, pmid = {31124390}, issn = {1607-8888}, mesh = {Animals ; Anxiety/*psychology ; Brain/metabolism ; Cytokines/metabolism ; Depression/*psychology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Hippocampus/metabolism ; Humans ; Inflammation ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; Stress, Psychological/physiopathology ; }, abstract = {Recent studies have demonstrated that there are significant changes in the gut microbiota (GM) of humans with depression and animal models of depression and chronic stress. In our present study, we determined whether an alteration in GM is a decisive factor in anxiety-like and depression-like behavior and its impact on brain neurochemistry. An antibiotic cocktail was used to deplete the GM of mice before they were colonized, via fecal microbiota transplantation (FMT), by the GM of control mice or mice that had been exposed to chronic unpredictable mild stress (CUMS donors). The CUMS-donor group of mice and the mice that were colonized by their microbiota (the CUMS-recipient group) both showed higher levels of anxiety- and depression-like behavior compared to the controls. The GM community of the CUMS-donor and CUMS-recipient was distinctively different from the controls, with the CUMS group characterized by a lower relative abundance of Lactobacillus and a higher relative abundance of Akkermansia. Interestingly, FMT affected both behavior and neuroinflammation. Mice given the CUMS microbiota had significant elevations of interferon-γ (IFN-γ) and the tumor necrosis factor-alpha (TNF-α) in the hippocampus, which were accompanied by upregulated indoleamine 2,3-dioxygenase 1 (IDO1) in the hippocampus. These results suggest that GM modulates pro-inflammatory cytokines in the hippocampus through dysfunctional microbiota-gut-brain axis, exacerbating anxiety- and depression-like phenotypes. Key Points Chronic unpredictable mild stress increased anxiety- and depression-like behavior in mice. Mice colonized with gut microbiota (GM) from stressed mice showed similar behaviors. The GM composition of the donor and recipient mice was also comparable. Their relative pattern of two bacteria has been tied to neuroinflammatory activity. The results suggest a link between GM, brain function, and anxiety and depression.}, }
@article {pmid31123874, year = {2019}, author = {Yousi, F and Kainan, C and Junnan, Z and Chuanxing, X and Lina, F and Bangzhou, Z and Jianlin, R and Baishan, F}, title = {Evaluation of the effects of four media on human intestinal microbiota culture in vitro.}, journal = {AMB Express}, volume = {9}, number = {1}, pages = {69}, pmid = {31123874}, issn = {2191-0855}, support = {81770558//National Natural Science Foundation of China/ ; }, abstract = {The human intestinal microbiota has an important role in the maintenance of human health and disease pathogenesis. The aim of this research was to investigate the impact of four media on human intestinal microbiota metabolite and composition changes, we performed in vitro batch culture using intestinal microbiota samples from three fecal microbiota transplantation (FMT) donors. After 48 h culture, gut microbiota medium (GMM) had the highest production of acetic acid (73.00 ± 7.56 mM) and propionic acid (16.79 ± 1.59 mM), bacterial growth media (BGM) had the highest production of butyric acid (13.39 ± 0.56 mM). In addition, brain heart infusion (BHI) promoted (p < 0.05) the growth of Bacteroidetes, especially Bacteroides after 48 h, GMM resulted in a significant increase (p < 0.05) in Actinobacteria and increased the beneficial genus Bifidobacterium, fastidious anaerobe broth (FAB) increased Firmicutes population, and BGM promoted the growth of Escherichia-Shigella and Akkermansia. The results suggest that four media had different effects on the human intestinal microbiota metabolism and composition in vitro. These results may facilitate the culture of bacteria from the human intestinal microbiota.}, }
@article {pmid31123416, year = {2019}, author = {Terpstra, ML and Sinnige, MJ and Hugenholtz, F and Peters-Sengers, H and Remmerswaal, EB and Geerlings, SE and Bemelman, FJ}, title = {Butyrate production in patients with end-stage renal disease.}, journal = {International journal of nephrology and renovascular disease}, volume = {12}, number = {}, pages = {87-101}, pmid = {31123416}, issn = {1178-7058}, abstract = {Background: Chronic kidney disease (CKD) is associated with a decreased intestinal barrier function, causing bacterial translocation over the intestinal wall and triggering a systemic inflammatory response. Butyrate, a short-chain fatty acid produced by certain bacterial strains, is considered instrumental to keep the intestinal barrier intact. There are indications that a decreased amount of these specific bacterial species is part of the cause of the decreased intestinal barrier function in CKD. The aim of this study is (i) to determine if Dutch patients with end-stage renal disease (ESRD) have a decreased amount of butyrate-producing species and butyrate-producing capacity and (ii) whether this correlates with systemic inflammation. Methods: We used qPCR to evaluate the most abundant butyrate-producing species F. prauznitzii, E. rectale and Roseburia spp. and the BCoAT gene, which reflects the butyrogenic capacity of the intestinal microbiota. Fecal samples were collected from healthy kidney donors (n=15), preemptive renal transplant recipients (n=4) and dialysis patients (n=31). Markers of inflammation (CRP and IL-6) and intestinal permeability (D-lactate) were measured in plasma. Results: Patients with ESRD did not have a significantly decreased amount F. prauznitzii, E. rectale and Roseburia spp. or the BCoAT gene. Neither was there a significant correlation with CRP, IL-6 or D-lactate. On the individual level, there were some patients with decreased BCoAT levels and increased levels of CRP, IL-6 and D-lactate. Conclusions: Patients with ESRD do not have a decreased amount of the most abundant butyrate-producing species nor a decreased butyrate-producing capacity.}, }
@article {pmid31123221, year = {2019}, author = {Yu, F and Han, W and Zhan, G and Li, S and Xiang, S and Zhu, B and Jiang, X and Yang, L and Luo, A and Hua, F and Yang, C}, title = {Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice.}, journal = {Aging}, volume = {11}, number = {10}, pages = {3262-3279}, pmid = {31123221}, issn = {1945-4589}, mesh = {Animals ; Cognitive Dysfunction/*etiology ; Diabetes Mellitus, Experimental/*complications/microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; *Spatial Memory ; }, abstract = {Both diabetes and Alzheimer's disease are age-related disorders, and numerous studies have demonstrated that patients with diabetes are at an increased risk of cognitive dysfunction (CD) and Alzheimer's disease, suggesting shared or interacting pathomechanisms. The present study investigated the role of abnormal gut microbiota in diabetes-induced CD and the potential underlying mechanisms. An intraperitoneal injection of streptozotocin administered for 5 consecutive days was used for establishing a diabetic animal model. Hierarchical cluster analysis of Morris water maze (MWM) performance indices (escape latency and target quadrant crossing) was adopted to classify the diabetic model mice into CD and Non-CD phenotypes. Both β-diversity and relative abundance of several gut bacteria significantly differed between the CD and Non-CD groups. Further, fecal bacteria transplantation from Non-CD mice, but not from CD mice, into the gut of pseudo-germ-free mice significantly improved host MWM performance, an effect associated with alterations in β-diversity and relative abundance of host gut bacteria. Collectively, these findings suggest that abnormal gut microbiota composition contributes to the onset of diabetes-induced CD and that improving gut microbiota composition is a potential therapeutic strategy for diabetes and related comorbidities.}, }
@article {pmid31122134, year = {2020}, author = {McSweeney, B and Allegretti, JR and Fischer, M and Xu, H and Goodman, KJ and Monaghan, T and McLeod, C and Mullish, BH and Petrof, EO and Phelps, EL and Chis, R and Edmison, A and Juby, A and Ennis-Davis, R and Roach, B and Wong, K and Kao, D}, title = {In search of stool donors: a multicenter study of prior knowledge, perceptions, motivators, and deterrents among potential donors for fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {11}, number = {1}, pages = {51-62}, pmid = {31122134}, issn = {1949-0984}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Canada ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*statistics &amp; numerical data ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Surveys and Questionnaires ; Tissue Donors/*statistics &amp; numerical data ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.}, }
@article {pmid31119397, year = {2019}, author = {Contreras, GA and Munita, JM and Arias, CA}, title = {Novel Strategies for the Management of Vancomycin-Resistant Enterococcal Infections.}, journal = {Current infectious disease reports}, volume = {21}, number = {7}, pages = {22}, pmid = {31119397}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens that commonly affect critically ill patients. VRE have a remarkable genetic plasticity allowing them to acquire genes associated with antimicrobial resistance. Therefore, the treatment of deep-seated infections due to VRE has become a challenge for the clinician. The purpose of this review is to assess the current and future strategies for the management of recalcitrant deep-seated VRE infections and efforts for infection control in the hospital setting.<br><br>RECENT FINDINGS: Preventing colonization and decolonization of multidrug-resistant bacteria are becoming the most promising novel strategies to control and eradicate VRE from the hospital environment. Fecal microbiota transplantation (FMT) has shown remarkable results on treating colonization and infection due to Clostridiodes difficille and VRE, as well as to recover the integrity of the gut microbiota under antibiotic pressure. Initial reports have shown the efficacy of FMT on reestablishing patient microbiota diversity in the gut and reducing the dominance of VRE in the gastrointestinal tract. In addition, the use of bacteriophages may be a promising strategy in eradicating VRE from the gut of patients. Until these strategies become widely available in the hospital setting, the implementation of infection control measures and stewardship programs are paramount for the control of this pathogen and each program should provide recommendations for the proper use of antibiotics and develop strategies that help to detect populations at risk of VRE colonization, prevent and control nosocomial transmission of VRE, and develop educational programs for all healthcare workers addressing the epidemiology of VRE and the potential impact of these pathogens on the cost and outcomes of patients. In terms of antibiotic strategies, daptomycin has become the standard of care for the management of deep-seated infections due to VRE. However, recent evidence indicates that the efficacy of this antibiotic is limited, and higher (10-12&#xa0;mg/kg) doses and/or combination with &#x3b2;-lactams is needed for therapeutic success. Clinical data to support the best use of daptomycin against VRE are urgently needed. This review provides an overview of recent developments regarding the prevention, treatment, control, and eradication of VRE in the hospital setting. We aim to provide an update of the most recent therapeutic strategies to treat deep-seated infections due to VRE.}, }
@article {pmid31117340, year = {2019}, author = {Cho, JM and Pestana, L and Pardi, R and Pardi, DS and Khanna, S}, title = {Fecal microbiota transplant via colonoscopy may be preferred due to intraprocedure findings.}, journal = {Intestinal research}, volume = {17}, number = {3}, pages = {434-437}, pmid = {31117340}, issn = {1598-9100}, }
@article {pmid31116134, year = {2019}, author = {Revolinski, SL and Munoz-Price, LS}, title = {Clostridioides difficile in transplant patients: early diagnosis, treatment, and prevention.}, journal = {Current opinion in infectious diseases}, volume = {32}, number = {4}, pages = {307-313}, doi = {10.1097/QCO.0000000000000560}, pmid = {31116134}, issn = {1473-6527}, mesh = {Anti-Bacterial Agents/pharmacology/*therapeutic use ; Antibiotic Prophylaxis ; *Clostridioides difficile ; Clostridium Infections/*diagnosis/*etiology/prevention &amp; control/*therapy ; Disease Management ; Early Diagnosis ; Humans ; Organ Transplantation/*adverse effects/methods ; *Transplant Recipients ; }, abstract = {PURPOSE OF REVIEW: Clostridioides difficile infection is common in solid organ transplant and hematopoietic stem-cell transplant recipients and is associated with significant morbidity and mortality. These populations are also underrepresented in clinical trials, making optimal management difficult. Because of this, management of these populations follows national guideline recommendations. This review aims to summarize the recent relevant literature pertaining to the clinical management of C. difficile infection in transplant patients, with a particular focus on diagnosis, treatment, and prevention.<br><br>RECENT FINDINGS: Early diagnosis of C. difficile colonization may mitigate both horizontal and vertical transmission (progression from colonization to colitis) of infection. Once diagnosed, recent literature suggests antibiotic treatment should align with that recommended by national guidelines. Fecal microbiota transplant is an emerging therapy for recurrent C. difficile infection, and recent data have demonstrated safety and efficacy. Prevention strategies including antimicrobial stewardship, probiotic administration, antibiotic administration, and bezlotoxumab may be beneficial in transplant populations, but more data are needed to confirm recent findings.<br><br>SUMMARY: Studies evaluating C. difficile infection in transplant patients are only recently starting to emerge. Further research is needed to identify optimal treatment and prevention strategies, and to examine novel strategies such as microbiome manipulation.}, }
@article {pmid31113785, year = {2019}, author = {Krensky, C and Poutanen, SM and Hota, SS}, title = {Diarrhea after fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {191}, number = {20}, pages = {E559-E561}, pmid = {31113785}, issn = {1488-2329}, mesh = {Adult ; Clostridioides difficile ; Clostridium Infections/*therapy ; Diarrhea/*etiology ; Fecal Microbiota Transplantation/*adverse effects ; Female ; Humans ; Recurrence ; Treatment Outcome ; }, }
@article {pmid31109076, year = {2019}, author = {Primadharsini, PP and Nagashima, S and Okamoto, H}, title = {Genetic Variability and Evolution of Hepatitis E Virus.}, journal = {Viruses}, volume = {11}, number = {5}, pages = {}, pmid = {31109076}, issn = {1999-4915}, mesh = {Animals ; *Evolution, Molecular ; *Genetic Variation ; Genome, Viral ; Genomics/methods ; Genotype ; Hepatitis E/*virology ; Hepatitis E virus/classification/*genetics ; Humans ; Phylogeny ; }, abstract = {Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus. HEV can cause both acute and chronic hepatitis, with the latter usually occurring in immunocompromised patients. Modes of transmission range from the classic fecal-oral route or zoonotic route, to relatively recently recognized but increasingly common routes, such as via the transfusion of blood products or organ transplantation. Extrahepatic manifestations, such as neurological, kidney and hematological abnormalities, have been documented in some limited cases, typically in patients with immune suppression. HEV has demonstrated extensive genomic diversity and a variety of HEV strains have been identified worldwide from human populations as well as growing numbers of animal species. The genetic variability and constant evolution of HEV contribute to its physiopathogenesis and adaptation to new hosts. This review describes the recent classification of the Hepeviridae family, global genotype distribution, clinical significance of HEV genotype and genomic variability and evolution of HEV.}, }
@article {pmid31108371, year = {2019}, author = {Beirão, J and Boulais, M and Gallego, V and O'Brien, JK and Peixoto, S and Robeck, TR and Cabrita, E}, title = {Sperm handling in aquatic animals for artificial reproduction.}, journal = {Theriogenology}, volume = {133}, number = {}, pages = {161-178}, doi = {10.1016/j.theriogenology.2019.05.004}, pmid = {31108371}, issn = {1879-3231}, mesh = {Animals ; Aquatic Organisms/*physiology ; Crassostrea ; Fishes ; Insemination, Artificial/veterinary ; Male ; Mammals ; Penaeidae ; Semen Preservation/veterinary ; Specimen Handling/methods/*veterinary ; Sperm Retrieval/*veterinary ; }, abstract = {Artificial reproduction involves collection and handling of gametes in a way that secures their quality and maximizes the fertilization outcome. In addition to initial sperm quality, numerous steps can affect the final result of fertilization, from the sperm collection process until gamete mixing (or co-incubation) when the spermatozoon enters or fuses with the oocyte. In this review, we summarize the whole process of sperm handling, from collection until fertilization for fish, penaeid shrimp, bivalve mollusks and marine mammals. To obtain sperm from captive animals, techniques vary widely across taxa, and include stripping by abdominal massage or testis surgical removal in fish, spermatophore collection in penaeid shrimps, gonadal scarification or temperature shock in bivalve mollusks, and voluntary collection via positive reinforcement in mammals. In most cases, special care is needed to avoid contamination by mucus, seawater, urine, or feces that can either activate sperm motility and/or decrease its quality. We also review techniques and extender solutions used for refrigerated storage of sperm across the aforementioned taxa. Finally, we give an overview of the different protocols for in vivo and in vitro fertilization including activation of sperm motility and methods for gamete co-incubation. The present study provides valuable information regarding breeder management either for animal production or species conservation.}, }
@article {pmid31105775, year = {2019}, author = {López Romo, A and Quirós, R}, title = {Appropriate use of antibiotics: an unmet need.}, journal = {Therapeutic advances in urology}, volume = {11}, number = {}, pages = {1756287219832174}, pmid = {31105775}, issn = {1756-2872}, abstract = {Increasing bacterial resistance combined with a steady decline in the discovery of new antibiotics has resulted in a global healthcare crisis. Overuse of antibiotics, for example, in the poultry and cattle industry, and misuse and improper prescription of antibiotics are leading causes of multidrug resistance (MDR). The increasing use of antibiotics, particularly in developing countries, is a big concern for antibiotic resistance and can cause other health threats such as increased risk of recurrent infections and increased risk of cardiovascular death with chronic use of macrolides. Carbapenems are the last line of defense in many cases of resistant infection, but trends show that resistance against these agents is also increasing. This narrative review is based on relevant literature according to the experience and expertise of the authors and presents an overview of the current knowledge on antibiotic resistance, the key driving factors, and possible strategies to tackle antibiotic resistance. Collectively, studies show that hospital-wide antibiotic stewardship programs are effective in decreasing the spread of antibacterial resistance. As resistance varies according to local patterns of use, it is essential to observe the epidemiology at both a regional and an institutional level. Furthermore, adaptation of clinical guidelines is necessary, particularly for inpatient care. Future guidelines should include a justification step for continued treatment of antibiotic treatments and criteria for selection of antibiotics at the start of treatment. Nonantibiotic prevention strategies can limit infections and should also be considered in treatment plans. Vaccines against MDR organisms have shown some efficacy in phase II trials in critical care patients. Nonimmunogenic and microbiologic treatment options such as fecal transplants may be particularly important for elderly and immune-compromised patients.}, }
@article {pmid31105766, year = {2019}, author = {Saha, S and Khanna, S}, title = {Management of Clostridioides difficile colitis: insights for the gastroenterologist.}, journal = {Therapeutic advances in gastroenterology}, volume = {12}, number = {}, pages = {1756284819847651}, pmid = {31105766}, issn = {1756-283X}, abstract = {Clostridioides difficile infection (CDI) is a common cause of diarrhea in both inpatient and outpatient settings. The last few years have seen major changes in the treatment spectrum of CDI, most notably, recommendations against using metronidazole for initial CDI, the addition of fidaxomicin and bezlotoxumab, and emergence of microbial replacement therapies. Several other therapies are undergoing clinical trials. This narrative review focuses on the treatment of CDI with a summary of literature on the newer modalities and the treatment guidelines issued by Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases.}, }
@article {pmid31105675, year = {2019}, author = {Wang, J and Lang, T and Shen, J and Dai, J and Tian, L and Wang, X}, title = {Core Gut Bacteria Analysis of Healthy Mice.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {887}, pmid = {31105675}, issn = {1664-302X}, abstract = {Previous studies revealed that there existed great individual variations of gut microbiota in mice, and the gut bacteria of mice were changed with the occurrence and development of diseases. To identify the core gut bacteria in healthy mice and explore their relationships with the host phenotypes would help to understand the underlying mechanisms. In this study, we identified 37 genus-level core bacteria from feces of 101 healthy mice with different ages, sexes, and mouse strains in three previous studies. They collectively represented nearly half of the total sequences, and predominantly included carbohydrate- and amino acids-metabolizing bacteria and immunomodulatory bacteria. Among them, Anaerostipes indwelt the gut of all healthy mice. Co-abundance analysis showed that these core genera were clustered into five groups (Group C1-C5), which were ecologically related. For example, the abundances of Group C2 including probiotics Bifidobacterium and Lactobacillus slightly positively correlated with those of Group C1. Principal component analysis (PCA) and multivariate analysis of variance test revealed that these core gut genera were distinguished with age and sex, and also associated with their health/disease state. Linear discriminant analysis effect size (LEfSe) method showed that bacteria in Group C1 and C2/C3 increased with the age in infancy and early adulthood, and were more abundant in female mice than in male ones. The metabolic syndrome (MS) induced by high fat diet (HFD) and accelerated postnatal growth would decrease Group C2 genera, whereas probiotics intervention would reverse HFD-induced reduction of Group C2. Spearman correlation analysis indicated that the principal components based on the abundance of the 37 core genera were significantly correlated with host characteristic parameters of MS. These results demonstrated that the 37 core genera in five co-abundance groups from healthy mice were related to host phenotypes. It was indicated that these prevalent gut bacterial genera could be representative of the healthy gut microbiome in gnotobiotic animal models, and might also be candidates of probiotics and fecal microbiota transplantation.}, }
@article {pmid31103793, year = {2019}, author = {Dailey, FE and Turse, EP and Daglilar, E and Tahan, V}, title = {The dirty aspects of fecal microbiota transplantation: a review of its adverse effects and complications.}, journal = {Current opinion in pharmacology}, volume = {49}, number = {}, pages = {29-33}, doi = {10.1016/j.coph.2019.04.008}, pmid = {31103793}, issn = {1471-4973}, mesh = {Animals ; Fecal Microbiota Transplantation/*adverse effects/mortality ; Humans ; Immunocompromised Host ; Risk ; }, abstract = {Fecal microbiota transplantation is becoming a growing therapy for a variety of indications, including recurrent or refractory Clostridium difficile infection (CDI), as well as many other gastrointestinal and extra-intestinal diseases. In fact, fecal microbiota transplantation is now strongly recommended as the treatment of choice for multiple recurrences of CDI, given its strong efficacy and a favorable short-term side effect profile. As the application of this therapy expands, awareness of its adverse events has also developed. The purpose of this review is to bring to light the side effects and complications associated with fecal microbiota transplantation, with an emphasis on findings from recently published studies.}, }
@article {pmid31097468, year = {2019}, author = {Dodiya, HB and Kuntz, T and Shaik, SM and Baufeld, C and Leibowitz, J and Zhang, X and Gottel, N and Zhang, X and Butovsky, O and Gilbert, JA and Sisodia, SS}, title = {Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes.}, journal = {The Journal of experimental medicine}, volume = {216}, number = {7}, pages = {1542-1560}, pmid = {31097468}, issn = {1540-9538}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R21 NS101673/NS/NINDS NIH HHS/United States ; R01 NS088137/NS/NINDS NIH HHS/United States ; R01 AG054672/AG/NIA NIH HHS/United States ; R21 NS104609/NS/NINDS NIH HHS/United States ; R01 AG051812/AG/NIA NIH HHS/United States ; }, mesh = {Amyloid Neuropathies/*pathology ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Anti-Bacterial Agents/adverse effects ; Brain Diseases/*pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome/drug effects/physiology ; Male ; Mice ; Microglia/*pathology ; Plaque, Amyloid/metabolism ; Sex Factors ; }, abstract = {We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE /presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the "M0" homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis.}, }
@article {pmid31095511, year = {2019}, author = {Sasmita, AO}, title = {Modification of the gut microbiome to combat neurodegeneration.}, journal = {Reviews in the neurosciences}, volume = {30}, number = {8}, pages = {795-805}, doi = {10.1515/revneuro-2019-0005}, pmid = {31095511}, issn = {2191-0200}, mesh = {Alzheimer Disease/etiology/*microbiology/therapy ; Amyotrophic Lateral Sclerosis/etiology/*microbiology/therapy ; Animals ; *Gastrointestinal Microbiome ; Humans ; Multiple Sclerosis/etiology/*microbiology/therapy ; Parkinson Disease/etiology/*microbiology/therapy ; Probiotics/*therapeutic use ; }, abstract = {The gut microbiome was extensively researched for its biological variety and its potential role in propagating diseases outside of the gastrointestinal (GI) tract. Recently, a lot of effort was focused on comprehending the gut-brain axis and the bizarre communication between the GI system and the nervous system. Ample amount of studies being carried out also revealed the involvement of the gut microbiome in enhancing the degree of many neurological disorders, including neurodegenerative diseases. It was widely observed that there were distinct microbiome profiles and dysbiosis within patients suffering from Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Various approaches to re-establish the balance of the gut microbiome, from antibiotic therapy, fecal microbiota transplant, or ingestion of psychobiotics, are discussed within this review within the specific context of combating neurodegenerative diseases. Present studies and clinical trials indicate that although there is an immense potential of gut microbiome modification to be preventive or therapeutic, there are still many intercalated components of the gut-brain axis at play and thus, more research needs to be carried out to delineate microbiome factors that may potentially alleviate symptoms of neurodegeneration.}, }
@article {pmid31094420, year = {2019}, author = {Lee, C and Hong, SN and Paik, NY and Kim, TJ and Kim, ER and Chang, DK and Kim, YH}, title = {CD1d Modulates Colonic Inflammation in NOD2-/- Mice by Altering the Intestinal Microbial Composition Comprising Acetatifactor muris.}, journal = {Journal of Crohn's &amp; colitis}, volume = {13}, number = {8}, pages = {1081-1091}, doi = {10.1093/ecco-jcc/jjz025}, pmid = {31094420}, issn = {1876-4479}, mesh = {Animals ; Antigens, CD1d/*immunology ; *Clostridiales/immunology/isolation &amp; purification ; Disease Models, Animal ; Gastrointestinal Microbiome/*immunology ; Inflammation/immunology ; Inflammatory Bowel Diseases/*immunology/pathology ; Mice ; Nod2 Signaling Adaptor Protein/*immunology ; Paneth Cells/*immunology ; }, abstract = {AIMS: NOD2 and CD1d play a key role in innate immunity by recognizing conserved molecular patterns of pathogens. While NOD2-/- and CD1d-/- mice display structural and functional alterations in Paneth cells, animal studies have reported no impact of NOD2 or CD1d deficiency on experimental colitis. NOD2 mutations increase the susceptibility to inflammatory bowel diseases and the CD1d bound to α-galactosylceramide [α-GalCer] alleviates intestinal inflammation. We evaluated the effect of CD1d modulation on experimental colitis in NOD2-/- mice.<br><br>METHODS: The effect of CD1d augmentation and depletion in NOD2-/- mice was assessed in a dextran sodium sulphate [DSS]-induced colitis model via administration of &#x3b1;-GalCer and construction of NOD2-/-CD1d-/- mice. The structural and functional changes in Paneth cells were evaluated using transmission electron microscopy and pilocarpine administration. Colitogenic taxa were analysed in the faeces of NOD2-/-CD1d-/- mice using 16S rRNA gene sequencing.<br><br>RESULTS: In NOD2-/- mice, &#x3b1;-GalCer alleviated and CD1d depletion [NOD2-/-CD1d-/- mice] aggravated colitis activity and histology compared with co-housed littermates NOD2-/-, CD1d-/- and wild-type mice after administration of 3% DSS. In NOD2-/-CD1d-/- mice, the ultrastructure and degranulation ability of secretary granules in Paneth cells were altered and the intestinal microbial composition differed from that of their littermates. Faecal microbiota transplantation [FMT] with NOD2-/-CD1d-/- mice faeces into wild-type mice aggravated DSS-induced colitis, while FMT with wild-type mice faeces into NOD2-/-CD1d-/- mice alleviated DSS-induced colitis. Acetatifactor muris was identified only in NOD2-/-CD1d-/- mice faeces and the oral gavage of A. muris in wild-type mice aggravated DSS-induced colitis.<br><br>CONCLUSION: CD1d modulates colonic inflammation in NOD2-/- mice by altering the intestinal microbial composition comprising A. muris.}, }
@article {pmid31091761, year = {2019}, author = {Noce, A and Marrone, G and Di Daniele, F and Ottaviani, E and Wilson Jones, G and Bernini, R and Romani, A and Rovella, V}, title = {Impact of Gut Microbiota Composition on Onset and Progression of Chronic Non-Communicable Diseases.}, journal = {Nutrients}, volume = {11}, number = {5}, pages = {}, pmid = {31091761}, issn = {2072-6643}, mesh = {Animals ; *Diabetes Mellitus ; *Gastrointestinal Microbiome ; Humans ; *Hypertension ; *Noncommunicable Diseases ; *Probiotics ; *Renal Insufficiency, Chronic ; }, abstract = {In recent years, mounting scientific evidence has emerged regarding the evaluation of the putative correlation between the gut microbiota composition and the presence of chronic non-communicable diseases (NCDs), such as diabetes mellitus, chronic kidney disease, and arterial hypertension. The aim of this narrative review is to examine the current literature with respect to the relationship between intestinal dysbiosis and the insurgence/progression of chronic NCDs, analyzing the physiopathological mechanisms that can induce microbiota modification in the course of these pathologies, and the possible effect induced by microbiota alteration upon disease onset. Therapy based on probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplant can represent a useful therapeutic tool, as has been highlighted on animal studies. To this moment, clinical studies that intended to demonstrate the beneficial effect induced by this kind of oral supplementation on the gut microbiota composition, and subsequent amelioration of signs and symptoms of chronic NCDs have been conducted on limited sample populations for a limited follow-up period. Therefore, to fully evaluate the therapeutic value of this kind of intervention, it would be ideal to design ample population; randomized clinical trials with a lengthy follow up period.}, }
@article {pmid31088542, year = {2019}, author = {Prevel, R and Boyer, A and M'Zali, F and Lasheras, A and Zahar, JR and Rogues, AM and Gruson, D}, title = {Is systematic fecal carriage screening of extended-spectrum beta-lactamase-producing Enterobacteriaceae still useful in intensive care unit: a systematic review.}, journal = {Critical care (London, England)}, volume = {23}, number = {1}, pages = {170}, pmid = {31088542}, issn = {1466-609X}, mesh = {Adult ; Carrier State/*diagnosis/physiopathology ; Cross Infection/prevention &amp; control ; Enterobacteriaceae/metabolism/pathogenicity ; Enterobacteriaceae Infections/diagnosis/physiopathology/prevention &amp; control ; Feces/*microbiology ; Female ; Humans ; Intensive Care Units/organization &amp; administration ; Male ; Mass Screening/*methods/trends ; Microbial Sensitivity Tests/methods ; beta-Lactamases/adverse effects/*analysis/metabolism ; }, abstract = {BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are disseminating worldwide leading to increased hospital length of stay and mortality in intensive care units (ICU). ESBL-E dissemination was first due to outbreaks in hospital settings which led to the implementation of systematic fecal carriage screening to improve hygiene procedures by contact precautions. ESBLs have since spread in the community, and the relevance of contact precautions is questioned. ESBL-E dissemination led to an overuse of carbapenems triggering the emergence of carbapenem-resistant Enterobacteriaceae. Empirical antimicrobial therapy based on ESBL-E fecal carriage has been proposed but is debated as it could increase the consumption of carbapenems among ESBL-E carriers without any clinical benefit. Finally, selective decontamination among ESBL-E fecal carriers is evoked to decrease the risk for subsequent ESBL-E infection, but its efficacy remains debated. We propose to systematically review the evidence to recommend or not such systematic ESBL-E fecal carriage screening in adult ICU.<br><br>METHODS: Every article focusing on ESBL-E and ICU available on the MEDLINE database was assessed. Articles were included if focusing on cross-transmission, efficacy of hygiene procedures, link between ESBL-E colonization and infection or guidance of empirical therapy or selective decontamination efficacy.<br><br>RESULTS: Among 330 articles referenced on PubMed, 39 abstracts were selected for full-text assessment and 25 studies were included. Systematic screening of ESBL-E fecal carriage to guide contact precautions do not seem to decrease the rate of ESBL-E cross-transmission. It has a very good negative predictive value for subsequent ESBL-E infections but a positive predictive value between 40 and 50% and so does not help to spare carbapenems. Cessation of ESBL-E carriage systematic screening could decrease the use of carbapenems in ICU without any clinical harm. Nevertheless, further studies are needed to validate these results from monocentric before-after study. Selective decontamination strategy applied to ESBL-E fecal carriers could be helpful, but available data are conflicting.<br><br>CONCLUSION: Current knowledge lacks of high-quality evidence to strongly recommend in favor of or against a systematic ESBL-E fecal carriage screening policy for ICU patients in a non-outbreak situation. Further evaluation of selective decontamination or fecal microbiota transplantation among ESBL-E fecal carriers is needed.}, }
@article {pmid31085417, year = {2019}, author = {Turse, EP and Dailey, FE and Ghouri, YA and Tahan, V}, title = {Fecal microbiota transplantation donation: the gift that keeps on giving.}, journal = {Current opinion in pharmacology}, volume = {49}, number = {}, pages = {24-28}, doi = {10.1016/j.coph.2019.04.009}, pmid = {31085417}, issn = {1471-4973}, mesh = {Costs and Cost Analysis ; *Fecal Microbiota Transplantation/economics ; Humans ; Risk Factors ; *Tissue Donors ; }, abstract = {Fecal microbiota transplantation (FMT) is being studied and utilized for various medical conditions including Clostridium difficile colitis, inflammatory bowel diseases (IBD), obesity, myasthenia gravis, and so on. Yet, FMT donation, whether from an individual or a stool bank, can be challenging given the numerous requirements and donor costs. Furthermore, data outcomes on recipients of FMT regarding donor's health co-morbidities, age, and weight are limited but emerging. The purpose of this review is to evaluate cost, safety, and accessibility in FMT donation.}, }
@article {pmid31082878, year = {2019}, author = {Shaukat, A and Brenner, DM}, title = {Fecal Microbiota Transplant for Irritable Bowel Syndrome: Panacea or Placebo?.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {7}, pages = {1032-1033}, doi = {10.14309/ajg.0000000000000259}, pmid = {31082878}, issn = {1572-0241}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome ; *Microbiota ; }, abstract = {Irritable bowel syndrome (IBS) is a common disorder of heterogeneous pathogenesis, and alterations in the gut microbiome/dysbiosis play a role in the development of symptoms in a subset of individuals with IBS. Consequently, it stands to reason that modulation of the microbiome via fecal microbial transplant (FMT) may serve as an effective treatment strategy because this has proven effective for treating other illnesses such as Clostridium difficile colitis. Small studies completed to date have offered conflicting results and the strains used, route of administration, and IBS subtypes may all play a role in treatment outcomes. A better understanding of the altered microbiome of patients with IBS and more rigorous trials are warranted before the utility of fecal microbial transplant for IBS symptoms can be determined.}, }
@article {pmid31078242, year = {2019}, author = {Fritsch, J and Abreu, MT}, title = {The Microbiota and the Immune Response: What Is the Chicken and What Is the Egg?.}, journal = {Gastrointestinal endoscopy clinics of North America}, volume = {29}, number = {3}, pages = {381-393}, doi = {10.1016/j.giec.2019.02.005}, pmid = {31078242}, issn = {1558-1950}, mesh = {Dysbiosis/*immunology ; Gastrointestinal Microbiome/*immunology ; Humans ; *Immunity, Mucosal ; Inflammation ; Inflammatory Bowel Diseases/*immunology/*microbiology ; }, abstract = {The underlying factors driving the onset and progression of inflammatory bowel disease (IBD) include the interplay between host genetics, microbiota, and mucosal inflammation. The same environmental triggers that are a risk factor for IBD also alter the microbiota, suggesting a link between the microbiome and IBD. Specific IBD-associated genetic polymorphisms change the microbiome linking host genetics to the microbiota. Microbial changes occur at least simultaneously with new onset IBD, and fecal microbial transplant can ameliorate certain types of IBD. A current debate in the field is which comes first, dysbiosis or inflammation? Can restitution of the microbiome "cure" IBD?}, }
@article {pmid31076926, year = {2019}, author = {Lin, C and Wan, J and Lu, Y and Zhang, H and Chen, X and Su, Y and Zhu, W}, title = {Active bacterial communities of pig fecal microbiota transplantation suspension prepared and preserved under different conditions.}, journal = {AMB Express}, volume = {9}, number = {1}, pages = {63}, pmid = {31076926}, issn = {2191-0855}, support = {31572414//National Natural Science Foundation of China/ ; 3187130113//National Natural Science Foundation of China/ ; 2018YFD0500404//National Key R &amp; D Program of China/ ; }, abstract = {Although fecal microbiota transplantation (FMT) has become a research hotspot, studies on comparison of the active fecal bacteria suspension under different preparation conditions are limited. This study investigated the abundances of active bacterial community in pig FMT suspension that produced under different oxygen concentrations or cryopreservation conditions. Fecal samples from a Landrace × Yorkshire sow were used to prepare fecal bacteria suspension under the anaerobic (AN group) and aerobic conditions (AE group), respectively. And then half of the anaerobic fecal bacteria suspension was cryopreservation in - 80 °C (AN-CR group) for 1 week. The microbial RNA in the fecal bacteria suspension was extracted before and after cryopreservation, and reverse transcribed into cDNA. MiSeq sequencing 16S rRNA gene of bacterial cDNA showed that the bacterial diversity in the AN group was significantly higher than that in the AE group. Comparing with the sows' fecal sample, the relative abundances of Lactobacillus johnsonii, Lactobacillus coleohominis and Parabacteroides merdae in AN, AE and AN-CR groups were reduced. The short-term cryopreservation had low impact on the structure of the active bacterial community in the fecal bacterial suspension. These results suggest that fecal bacteria suspension can be better prepared under strict anaerobic condition, and that fecal bacteria suspension can be cryopreserved in - 80 °C for a short time.}, }
@article {pmid31073525, year = {2019}, author = {Jia, Q and Zhang, L and Zhang, J and Pei, F and Zhu, S and Sun, Q and Duan, L}, title = {Fecal Microbiota of Diarrhea-Predominant Irritable Bowel Syndrome Patients Causes Hepatic Inflammation of Germ-Free Rats and Berberine Reverses It Partially.}, journal = {BioMed research international}, volume = {2019}, number = {}, pages = {4530203}, pmid = {31073525}, issn = {2314-6141}, mesh = {Animals ; Berberine/*administration &amp; dosage ; Bifidobacterium/drug effects/pathogenicity ; Diarrhea/*drug therapy/microbiology/pathology ; Disease Models, Animal ; Faecalibacterium/drug effects/pathogenicity ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/genetics ; Humans ; Inflammation/*drug therapy/microbiology/pathology ; Irritable Bowel Syndrome/*drug therapy/microbiology/pathology ; Kupffer Cells/drug effects/pathology ; Liver/microbiology/pathology ; Rats ; }, abstract = {Effects of the microbiome associated with diarrhea-predominant irritable bowel syndrome (IBS-D) on the gut have been reported, but no study has reported the effects of the IBS-D gut microbiome on the liver. We transplanted the fecal microbiota from an IBS-D patient and from a healthy volunteer to GF rats. The hepatic inflammation, serum biochemical parameters and metabolome, fecal microbiota profile, fecal short-chain fatty acids (SCFAs), and correlations among them before and after berberine intervention were assessed. Compared with the healthy control fecal microbiome transplantation (FMT) rats, the fecal microbiota of IBS-D patients induces significant Kupffer cell hyperplasia, hepatic sinusoid hypertrophy, and elevated levels of hepatic tumor necrosis factor-α and interferon-γ and decreases the synthesis of ALB in GF rats. This is possibly related to Faecalibacterium and Bifidobacterium attributable to fecal formate, acetate, and propionate levels, which are associated with the host linoleic acid pathway. Berberine can partially reverse the Kupffer cell hyperplasia, Faecalibacterium, fecal formate, acetate, and propionate by modulating the gut microbiome composition. These results may imply that IBS-D not only is an intestinal functional disorder but can cause liver inflammation, thus providing some implications regarding the clinical cognition and treatment of IBS-D.}, }
@article {pmid31072874, year = {2019}, author = {}, title = {Microbiota Manipulated to Enhance Immunity.}, journal = {Cancer discovery}, volume = {9}, number = {7}, pages = {822}, doi = {10.1158/2159-8290.CD-ND2019-004}, pmid = {31072874}, issn = {2159-8290}, mesh = {Antineoplastic Agents, Immunological/*therapeutic use ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunotherapy/methods ; Microbiota/*immunology ; Neoplasms/*immunology/microbiology/*therapy ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology ; }, abstract = {Oncologists are testing fecal transplants and other microbiome-based products in combination with checkpoint inhibitors in an effort to increase and enhance responses. However, questions remain about how the microbes affect host immunity and which preparations of bacteria are optimal.}, }
@article {pmid31070838, year = {2019}, author = {Huang, HL and Chen, HT and Luo, QL and Xu, HM and He, J and Li, YQ and Zhou, YL and Yao, F and Nie, YQ and Zhou, YJ}, title = {Relief of irritable bowel syndrome by fecal microbiota transplantation is associated with changes in diversity and composition of the gut microbiota.}, journal = {Journal of digestive diseases}, volume = {20}, number = {8}, pages = {401-408}, doi = {10.1111/1751-2980.12756}, pmid = {31070838}, issn = {1751-2980}, support = {20181A011007//Guangzhou General Science and Technology Project of Health and Family Planning/ ; 201707010275//Guangzhou Planned Project of Science and Technology/ ; 201904010132//Guangzhou Planned Project of Science and Technology/ ; 2018A030313676//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Adult ; Aged ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*microbiology/*therapy ; Male ; Middle Aged ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for refractory irritable bowel syndrome (IBS).<br><br>METHODS: Microbiota suspensions from feces of the donors were injected into the intestines of 30 Chinese patients with refractory IBS. Microbiota composition analysis and genomic DNA extraction of fecal samples obtained from these patients at baseline and 1&#x2009;month after FMT were performed. Clinical efficacy and safety of FMT were assessed using questionnaires covering four aspects of IBS therapeutic efficacy and assessment of adverse effects during a 6-month follow-up.<br><br>RESULTS: FMT improved IBS gastrointestinal symptoms and alleviated depression and anxiety, as shown by the improved IBS-QOL, IBS-SSS, GSRS, HAMA and HAMD scores at 1 month and 3 months after FMT. A total adverse event rate of FMT was 6.7% (2/30). Gut microbiota analysis revealed that FMT responders had a significantly higher Shannon diversity index before FMT than non-responders. In addition, analysis of differences in bacterial composition before and after FMT in responders showed specific abundance of the phyla Verrucomincrobia and Euryarchaeota at 1&#x2009;month after FMT. At the genus level, Methanobrevibacter and Akkermansia were the most abundant fecal microbiota 1&#x2009;month after FMT compared with those before FMT.<br><br>CONCLUSIONS: FMT may be an effective and safe therapeutic strategy for treating IBS that achieves a sustained clinical response 3-6 months after the first procedure. Changes in the diversity and dominant flora may contribute to its therapeutic effect.}, }
@article {pmid31070363, year = {2019}, author = {Lu, X and Liu, J and Zhang, N and Fu, Y and Zhang, Z and Li, Y and Wang, W and Li, Y and Shen, P and Cao, Y}, title = {Ripened Pu-erh Tea Extract Protects Mice from Obesity by Modulating Gut Microbiota Composition.}, journal = {Journal of agricultural and food chemistry}, volume = {67}, number = {25}, pages = {6978-6994}, doi = {10.1021/acs.jafc.8b04909}, pmid = {31070363}, issn = {1520-5118}, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification ; DNA, Bacterial/genetics ; *Gastrointestinal Microbiome ; Humans ; Intestines/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/*diet therapy/metabolism/microbiology ; Plant Extracts/*metabolism ; Protective Agents/*metabolism ; RNA, Ribosomal, 16S/genetics ; Tea/metabolism ; }, abstract = {Ripened Pu-erh tea extract contributes to reducing weight gain and fat accumulation; however, the role of gut microbiota on the antiobesity effect of ripened Pu-erh tea extract in obese mice remains unclear. This study aims to explore the role of alterations in gut microbes mediated by ripened Pu-erh tea extract in obese mice through 16S rRNA sequencing and a fecal transplant trial. Our results suggested that drinking water containing ripened Pu-erh tea extract could decrease weight gain, fat accumulation, adipose inflammation, the Firmicutes-to-Bacteroidetes ratio, and metabolic endotoxemia while, in the meantime, improving the intestinal barrier integrity in obese mice. Moreover, the fecal transplant trial indicated that feces from the donor mice treated with ripened Pu-erh tea extract could significantly modulate weight and metabolic syndrome in the recipient mice. Thus, our results indicated that gut microbiota can mediate the function of ripened Pu-erh tea extract against obesity; additionally, ripened Pu-erh tea extract can potentially prevent individuals from being obese through rebalancing the gut microbiota.}, }
@article {pmid31068891, year = {2019}, author = {Xia, GH and You, C and Gao, XX and Zeng, XL and Zhu, JJ and Xu, KY and Tan, CH and Xu, RT and Wu, QH and Zhou, HW and He, Y and Yin, J}, title = {Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke.}, journal = {Frontiers in neurology}, volume = {10}, number = {}, pages = {397}, pmid = {31068891}, issn = {1664-2295}, abstract = {Background: Significant dysbiosis occurs in the gut microbiome of stroke patients. Condensing these broad, complex changes into one index would greatly facilitate the clinical usage of gut microbiome data. Here, we formulated a gut microbiota index in patients with acute ischemic stroke based on their gut microbiota dysbiosis patterns and tested whether the index was correlated with brain injury and early outcome. Methods: A total of 104 patients with acute ischemic stroke and 90 healthy individuals were recruited, and their gut microbiotas were compared and to model a Stroke Dysbiosis Index (SDI), which representing stroke-associated dysbiosis patterns overall. Another 83 patients and 70 controls were recruited for validation. The association of SDI with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) and outcome (modified Rankin scale [mRS] score: favorable, 0-2; unfavorable, >2) at discharge was also assessed. A middle cerebral artery occlusion (MCAO) model was used in human flora-associated (HFA) animals to explore the causal relationship between gut dysbiosis and stroke outcome. Results: Eighteen genera were significantly different between stroke patients and healthy individuals. The SDI formula was devised based on these microbiome differences; SDI was significantly higher in stroke patients than in healthy controls. SDI alone discriminated stroke patients from controls with AUCs of 74.9% in the training cohort and 84.3% in the validation cohort. SDI was significantly and positively correlated with NIHSS score on admission and mRS score at discharge. Logistic regression analysis showed that SDI was an independent predictor of severe stroke (NIHSS ≥8) and early unfavorable outcome (mRS >2). Mice receiving fecal transplants from high-SDI patients developed severe brain injury with elevated IL-17[+] γδ T cells in gut compared to mice receiving transplants from low-SDI patients (all P < 0.05). Conclusions: We developed an index to measure gut microbiota dysbiosis in stroke patients; this index was significantly correlated with patients' outcome and was causally related to outcome in a mouse model of stroke. Our model facilitates the potential clinical application of gut microbiota data in stroke and adds quantitative evidence linking the gut microbiota to stroke.}, }
@article {pmid31066530, year = {2019}, author = {Gilbert, B and Schrenzel, J}, title = {[Fecal microbiota transplantation : current status and prospects].}, journal = {Revue medicale suisse}, volume = {15}, number = {650}, pages = {976-983}, pmid = {31066530}, issn = {1660-9379}, mesh = {*Clostridium Infections/therapy ; *Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Metabolic Diseases/therapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is approved as a safe and effective treatment of recurrent Clostridium difficile infections. The technique is now being studied for other indications, usually involving chronic inflammation, metabolic disorders, or autoimmunity, for which the gut microbiota appears to play a key role. We detail thereafter, according to their degree of evidence, the potential future indications, in which FMT has already been tried on Humans. Except for ulcerative colitis and metabolic syndrome, the methodology of the published trials is often insufficiently described and inhomogeneous. Further randomized placebo-controlled trials and standardization of practice will be needed to confirm these preliminary but encouraging results.}, }
@article {pmid31065565, year = {2019}, author = {Galloway-Peña, JR and Peterson, CB and Malik, F and Sahasrabhojane, PV and Shah, DP and Brumlow, CE and Carlin, LG and Chemaly, RF and Im, JS and Rondon, G and Felix, E and Veillon, L and Lorenzi, PL and Alousi, AM and Jenq, RR and Kontoyiannis, DP and Shpall, EJ and Shelburne, SA and Okhuysen, PC}, title = {Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study.}, journal = {Open forum infectious diseases}, volume = {6}, number = {5}, pages = {ofz173}, pmid = {31065565}, issn = {2328-8957}, support = {K01 AI143881/AI/NIAID NIH HHS/United States ; L30 CA209245/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; S10 OD012304/OD/NIH HHS/United States ; }, abstract = {BACKGROUND: Accumulating evidence suggests that the intestinal microbiome may dramatically affect the outcomes of hematopoietic stem cell transplant (HSCT) recipients. Providing 16S ribosomal RNA based microbiome characterization in a clinically actionable time frame is currently problematic. Thus, determination of microbial metabolites as surrogates for microbiome composition could offer practical biomarkers.<br><br>METHODS: Longitudinal fecal specimens (n = 451) were collected from 44 patients before HSCT through 100 days after transplantation, as well as 1-time samples from healthy volunteers (n = 18) as controls. Microbiota composition was determined using 16S ribosomal RNA V4 sequencing. Fecal indole and butyrate levels were determined using liquid chromatography tandem mass spectrometry.<br><br>RESULTS: Among HSCT recipients, both fecal indole and butyrate levels correlated with the Shannon diversity index at baseline (P = .02 and P = .002, respectively) and directly after transplantation (P = .006 and P < .001, respectively). Samples with high butyrate levels were enriched for Clostridiales, whereas samples containing high indole were also enriched for Bacteroidales. A lower Shannon diversity index at the time of engraftment was associated with increased incidence of acute intestinal graft-vs-host disease (iGVHD) (P = .02) and transplant-related deaths (P = .03). Although fecal metabolites were not associated with acute iGVHD or overall survival, patients contracting bloodstream infections within 30 days after transplantation had significantly lower levels of fecal butyrate (P = .03).<br><br>CONCLUSIONS: Longitudinal analysis of fecal microbiome and metabolites after HSCT identified butyrate and indole as potential surrogate markers for microbial diversity and specific taxa. Further studies are needed to ascertain whether fecal metabolites can be used as biomarkers of acute iGVHD or bacteremia after HSCT.}, }
@article {pmid31064848, year = {2019}, author = {Buchta Rosean, C and Bostic, RR and Ferey, JCM and Feng, TY and Azar, FN and Tung, KS and Dozmorov, MG and Smirnova, E and Bos, PD and Rutkowski, MR}, title = {Preexisting Commensal Dysbiosis Is a Host-Intrinsic Regulator of Tissue Inflammation and Tumor Cell Dissemination in Hormone Receptor-Positive Breast Cancer.}, journal = {Cancer research}, volume = {79}, number = {14}, pages = {3662-3675}, pmid = {31064848}, issn = {1538-7445}, support = {T32 AI007496/AI/NIAID NIH HHS/United States ; R01 CA262634/CA/NCI NIH HHS/United States ; P30 CA044579/CA/NCI NIH HHS/United States ; T35 AI060528/AI/NIAID NIH HHS/United States ; T32 GM139787/GM/NIGMS NIH HHS/United States ; }, mesh = {*Breast Neoplasms ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Symbiosis ; Tumor Microenvironment ; }, abstract = {It is unknown why some patients with hormone receptor-positive (HR[+]) breast cancer present with more aggressive and invasive disease. Metastatic dissemination occurs early in disease and is facilitated by cross-talk between the tumor and tissue environment, suggesting that undefined host-intrinsic factors enhance early dissemination and the probability of developing metastatic disease. Here, we have identified commensal dysbiosis as a host-intrinsic factor associated with metastatic dissemination. Using a mouse model of HR[+] mammary cancer, we demonstrate that a preestablished disruption of commensal homeostasis results in enhanced circulating tumor cells and subsequent dissemination to the tumor-draining lymph nodes and lungs. Commensal dysbiosis promoted early inflammation within the mammary gland that was sustained during HR[+] mammary tumor progression. Furthermore, dysbiosis enhanced fibrosis and collagen deposition both systemically and locally within the tumor microenvironment and induced significant myeloid infiltration into the mammary gland and breast tumor. These effects were recapitulated both by directly targeting gut microbes using nonabsorbable antibiotics and by fecal microbiota transplantation of dysbiotic cecal contents, demonstrating the direct impact of gut dysbiosis on mammary tumor dissemination. This study identifies dysbiosis as a preexisting, host-intrinsic regulator of tissue inflammation, myeloid recruitment, fibrosis, and dissemination of tumor cells in HR[+] breast cancer. SIGNIFICANCE: Identification of commensal dysbiosis as a host-intrinsic factor mediating evolution of metastatic breast cancer allows for development of interventions or diagnostic tools for patients at highest risk for developing metastatic disease.See related commentary by Ingman, p. 3539.}, }
@article {pmid31063075, year = {2019}, author = {Assimos, DG}, title = {Re: Fecal Transplant Modifies Urine Chemistry Risk Factors for Urinary Stone Disease.}, journal = {The Journal of urology}, volume = {202}, number = {2}, pages = {205}, doi = {10.1097/01.JU.0000559609.65417.2e}, pmid = {31063075}, issn = {1527-3792}, mesh = {Calcium Oxalate ; Fecal Microbiota Transplantation ; Humans ; Risk Factors ; *Urinary Calculi ; *Urologic Diseases ; }, }
@article {pmid31062535, year = {2019}, author = {Khayat, AA and Telega, GW}, title = {Persistent elevation of aminotransferases in liver transplant in association with chronic norovirus infection.}, journal = {Clinical and molecular hepatology}, volume = {25}, number = {4}, pages = {408-411}, pmid = {31062535}, issn = {2287-285X}, mesh = {Alanine Transaminase/*blood ; Aspartate Aminotransferases/*blood ; Caliciviridae Infections/*diagnosis ; Child ; Child, Preschool ; Chronic Disease ; Feces/virology ; Female ; Humans ; Immunoglobulins, Intravenous/administration &amp; dosage ; Liver/metabolism/pathology ; *Liver Transplantation ; Male ; }, }
@article {pmid31061423, year = {2019}, author = {García-Fernández, S and Frentrup, M and Steglich, M and Gonzaga, A and Cobo, M and López-Fresneña, N and Cobo, J and Morosini, MI and Cantón, R and Del Campo, R and Nübel, U}, title = {Whole-genome sequencing reveals nosocomial Clostridioides difficile transmission and a previously unsuspected epidemic scenario.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {6959}, pmid = {31061423}, issn = {2045-2322}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Child ; Child, Preschool ; Clostridioides difficile/drug effects/*genetics/isolation &amp; purification ; Clostridium Infections/epidemiology/microbiology/therapy/*transmission ; Fecal Microbiota Transplantation/methods ; Female ; *Genetic Variation ; *Genome, Bacterial ; Humans ; Male ; Middle Aged ; Whole Genome Sequencing/*methods ; Young Adult ; }, abstract = {To trace the routes and frequencies of transmission of Clostridioides difficile in a tertiary-care hospital in Madrid (Spain), we sequenced the genomes from all C. difficile isolates collected over 36 months (2014-2016) that were indistinguishable from any other isolate by PCR ribotyping. From a total of 589 C. difficile infection cases, we cultivated and PCR-ribotyped 367 C. difficile isolates (62%), of which 265 were genome-sequenced. Based on close relatedness of successively collected isolates (≤2 SNPs difference in their genomes), whole-genome sequencing revealed a total of 17 independent, putative transmission clusters, caused by various C. difficile strains and each containing 2 to 18 cases, none of which had been detected previously by standard epidemiological surveillance. Proportions of linked isolates varied widely among PCR ribotypes, from 3% (1/36) for ribotype 014/020 to 60% (12/20) for ribotype 027, suggesting differential aptitudes for nosocomial spread. Remarkably, only a minority (17%) of transmission recipients had direct ward contact to their presumed donors and specific C. difficile genome types frequently went undetectable for several months before re-emerging later, suggesting reservoirs for the pathogen outside of symptomatic patients. Taken together, our analysis based on genome sequencing suggested considerable within-hospital epidemic spread of C. difficile, even though epidemiological data initially had been inconspicuous.}, }
@article {pmid31059962, year = {2019}, author = {Zhang, F and Zhang, T and Zhu, H and Borody, TJ}, title = {Evolution of fecal microbiota transplantation in methodology and ethical issues.}, journal = {Current opinion in pharmacology}, volume = {49}, number = {}, pages = {11-16}, doi = {10.1016/j.coph.2019.04.004}, pmid = {31059962}, issn = {1471-4973}, mesh = {Donor Selection ; *Fecal Microbiota Transplantation/ethics/instrumentation/methods ; Humans ; Tissue Donors ; }, abstract = {Fecal microbiota transplantation (FMT), the core therapy for remodeling the gut microbiota with a long medical history, has gained great attention worldwide in recent years. Increasing studies have explored its indications, methodology, efficacy, safety, and ethics. Purified forms of FMT, using an automated method for the purification of fecal microbiota from stool, has become a reality. Colonic transendoscopic enteral tubing makes frequent FMT delivery into the whole colon feasible. This review focuses on the recent progress in laboratory preparation, updated clinical strategies, novel delivery methods, and ethical issues surrounding FMT in clinical studies.}, }
@article {pmid31058026, year = {2019}, author = {Malik, MN and Rafae, A and Durer, C and Durer, S and Anwer, F}, title = {Fecal Calprotectin as a Diagnostic and Prognostic Biomarker for Gastrointestinal Graft Versus Host Disease: A Systematic Review of Literature.}, journal = {Cureus}, volume = {11}, number = {2}, pages = {e4143}, pmid = {31058026}, issn = {2168-8184}, abstract = {The current practice for diagnosing graft versus host disease (GVHD) includes clinical or endoscopic evaluation of the patient. Clinical diagnosis is limited by an overlapping symptomatic spectrum with infectious causes, a common scenario in the post-transplant setting where an invasive procedure, such as endoscopy, is often impractical. We, therefore, evaluated the role of fecal calprotectin as a diagnostic as well as a prognostic biomarker for gastrointestinal GVHD (GI-GVHD) occurrence and severity in the post-hematopoietic transplant population. Following Prisma guidelines, we performed a systematic search of articles published after 2004 using the PubMed, Embase, Cochrane Library, and Web of Science databases. After a detailed screening, 10 studies involving a total of 494 patients were included. In the cohorts comparing median fecal calprotectin (mFC) level in GI-GVHD vs. non-GI-GVHD patients, the results indicated an increase in the mFC level in patients with GI-GVHD when compared to non-GI-GVHD patients. Similarly, an increase in the mFC level was seen in accordance with the severity of the disease. Moreover, corticosteroid-resistant patients had a higher mFC level as compared to corticosteroid-sensitive patients. Our study indicates that the mFC level can be used for diagnosing as well as predicting the treatment response to GI-GVHD. However, future randomized prospective trials involving larger populations are needed to further explore its significance.}, }
@article {pmid31057522, year = {2019}, author = {Fiedorová, K and Radvanský, M and Němcová, E and Grombiříková, H and Bosák, J and Černochová, M and Lexa, M and Šmajs, D and Freiberger, T}, title = {The Impact of DNA Extraction Methods on Stool Bacterial and Fungal Microbiota Community Recovery.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {821}, pmid = {31057522}, issn = {1664-302X}, abstract = {Our understanding of human gut microbiota in health and disease depends on accurate and reproducible microbial data acquisition. The critical step in this process is to apply an appropriate methodology to extract microbial DNA, since biases introduced during the DNA extraction process may result in inaccurate microbial representation. In this study, we attempted to find a DNA extraction protocol which could be effectively used to analyze both the bacterial and fungal community. We evaluated the effect of five DNA extraction methods (QIAamp DNA Stool Mini Kit, PureLink[TM] Microbiome DNA Purification Kit, ZR Fecal DNA MiniPrep[TM] Kit, NucleoSpin[®] DNA Stool Kit, and IHMS protocol Q) on bacterial and fungal gut microbiome recovery using (i) a defined system of germ-free mice feces spiked with bacterial or fungal strains, and (ii) non-spiked human feces. In our experimental setup, we confirmed that the examined methods significantly differed in efficiency and quality, which affected the identified stool microbiome composition. In addition, our results indicated that fungal DNA extraction might be prone to be affected by reagent/kit contamination, and thus an appropriate blank control should be included in mycobiome research. Overall, standardized IHMS protocol Q, recommended by the International Human Microbiome Consortium, performed the best when considering all the parameters analyzed, and thus could be applied not only in bacterial, but also in fungal microbiome research.}, }
@article {pmid31055584, year = {2019}, author = {Lynch, SM and Mu, J and Grady, JJ and Stevens, RG and Devers, TJ}, title = {Fecal Microbiota Transplantation for Clostridium difficile Infection: A One-Center Experience.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {37}, number = {6}, pages = {467-472}, doi = {10.1159/000499873}, pmid = {31055584}, issn = {1421-9875}, mesh = {Clostridioides difficile/*pathogenicity ; Clostridium Infections/*microbiology/*therapy ; Comorbidity ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Probability ; Tissue Donors ; Treatment Outcome ; }, abstract = {BACKGROUND: Clostridium difficile is a gram-positive, anaerobic, and spore-forming bacillus, which is responsible for the majority of antibiotic-associated diarrhea and colitis.<br><br>OBJECTIVE: Determine if fecal microbiota transplantation (FMT) is effective in a population sample from Connecticut.<br><br>METHODS: We report the clinical experience of 92 consecutive patients from one gastroenterology practice in central Connecticut treated by colonoscopy with FMT for infection with Clostridium difficile from 2012 to 2017. The analyses are based on clinical follow-up up to 3 months after the FMT procedure and on medical chart review.<br><br>RESULTS: Overall, complete recovery occurred in 86% of patients. As previously reported in a limited number of previous studies, community-acquired cases were more common than hospital-acquired cases, and community-acquired cases were more likely to be female.<br><br>CONCLUSIONS: Consistent with some previous reports, we found the following: the source of the donor for FMT did not make a difference in recovery: material from nonrelatives was as effective as from close relatives; and the presence of multiple comorbidities did not make a difference in recovery: patients with 2 or more comorbidities did as well as those with one or none.}, }
@article {pmid31054313, year = {2019}, author = {Khanna, S and Gerding, DN}, title = {Current and future trends in clostridioides (clostridium) difficile infection management.}, journal = {Anaerobe}, volume = {58}, number = {}, pages = {95-102}, doi = {10.1016/j.anaerobe.2019.04.010}, pmid = {31054313}, issn = {1095-8274}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/*therapy ; *Disease Management ; Fecal Microbiota Transplantation/*methods ; Humans ; Immunologic Factors/*therapeutic use ; }, abstract = {Current and future management of Clostridioides difficile infection (CDI) including antibiotic treatment is increasingly focused on preventive strategies, either prevention of recurrent CDI (rCDI) or primary prevention of CDI. In addition to newer narrow spectrum antibiotics and pulse dosing of antibiotic treatment, multiple widely differing approaches to prevention of CDI and rCDI are under clinical development or recently approved for clinical use. They include immunologics, both passive monoclonal antibodies and active vaccines targeted at C. difficile toxins, approaches to reduce antibiotic dysbiosis in the gut, microbiome restoration using fecal microbiome transplants (FMT) or biotherapeutic bacterial derivatives, and substitution of non-toxigenic C. difficile (NTCD) for toxigenic C. difficile. Newer antibiotics, monoclonal antibodies, and FMT are targeted at reducing rCDI whereas vaccines and reduction of antibiotic dysbiosis in the gut are targeted at prevention of primary CDI. Biotherapeutics may be used for prevention of either primary CDI or rCDI. Approaches such as monoclonal antibodies, FMT, and biotherapeutics provide rapid but transient preventive benefits, whereas vaccines require weeks to months to be effective, but will presumably provide long term prevention. More rapid but transient prevention strategies such as FMT and biotherapeutics could be used in combination with vaccines to provide both rapid and durable CDI prevention.}, }
@article {pmid31051514, year = {2019}, author = {Khoruts, A and Sadowsky, MJ}, title = {Letter to the Editor.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {69}, number = {12}, pages = {2232-2233}, doi = {10.1093/cid/ciz366}, pmid = {31051514}, issn = {1537-6591}, mesh = {*Clostridioides difficile ; *Fecal Microbiota Transplantation ; }, }
@article {pmid31051032, year = {2019}, author = {Khanna, S and Tariq, R and Pardi, DS}, title = {Reply to Khoruts and Sadowsky.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {69}, number = {12}, pages = {2233-2234}, doi = {10.1093/cid/ciz367}, pmid = {31051032}, issn = {1537-6591}, mesh = {*Clostridioides difficile ; Diagnostic Tests, Routine ; *Fecal Microbiota Transplantation ; }, }
@article {pmid31049232, year = {2019}, author = {Zhang, J and Ren, G and Li, M and Lu, P and Yi, S}, title = {The Effects of Fecal Donors with Different Feeding Patterns on Diarrhea in a Patient Undergoing Hematopoietic Stem Cell Transplantation.}, journal = {Case reports in hematology}, volume = {2019}, number = {}, pages = {4505238}, pmid = {31049232}, issn = {2090-6560}, abstract = {Almost 90% of patients undergoing hematopoietic stem cell transplantation (HSCT) experience diarrheal episodes, which represent a severe, often life-threatening complication for these patients. Although fecal microbiota transplantation (FMT) represents an alternative treatment option for infection-related diarrhea, the application of FMT in HSCT patients is greatly restricted for safety reasons. Furthermore, the therapeutic outcomes of FMT as a diarrhea treatment are somewhat related to the choice of the FMT donor. Here, we comprehensively profiled the dynamic changes in the intestinal microbiota after FMT from two donors with different feeding patterns and the same severely diarrheal recipient undergoing HSCT via a 45-day clinical observation. Importantly, no adverse events attributed to FMT were observed. The stool volume and frequency of the patient were reduced when we used feces from donor #1 (mixed feeding), but these changes were not observed after FMT from donor #2 (exclusive breastfeeding). Interestingly, no obvious differences in overall diversity (Shannon) or richness (Chao1) between the two donors were observed. Additionally, Bifidobacterium accounted for 29.9% and 18.1% of OTUs in the stools of donors #1 and #2, respectively. Lactobacillus accounted for 16.3% and 2.9% of the stools of donors #1 and #2, respectively. Furthermore, through longitudinal monitoring of the patient, we identified 6 OTUs that were particularly sensitive to the different FMT complements. Together, we present a case report suggesting that the overall diversity of the intestinal microbiota may not be the only important element in the selection of an effective FMT donor.}, }
@article {pmid31047909, year = {2019}, author = {Mantovani, A and Turino, T and Altomari, A and Lonardo, A and Zoppini, G and Valenti, L and Tilg, H and Byrne, CD and Targher, G}, title = {Association between Helicobacter pylori infection and risk of nonalcoholic fatty liver disease: An updated meta-analysis.}, journal = {Metabolism: clinical and experimental}, volume = {96}, number = {}, pages = {56-65}, doi = {10.1016/j.metabol.2019.04.012}, pmid = {31047909}, issn = {1532-8600}, mesh = {Helicobacter Infections/*complications/epidemiology ; *Helicobacter pylori ; Humans ; Incidence ; Non-alcoholic Fatty Liver Disease/epidemiology/*etiology ; Prevalence ; }, abstract = {BACKGROUND: Recent studies that have examined the association between Helicobacter pylori infection and risk of nonalcoholic fatty liver disease (NAFLD) have produced conflicting data. We have performed a systematic review and meta-analysis to assess the association between H. pylori infection and risk of NAFLD.<br><br>METHODS: We searched PubMed, Web of Science and Scopus databases using predefined keywords to identify observational studies (published up to November 2018), in which NAFLD was diagnosed by histology, imaging or biochemistry. Data from selected studies were extracted and meta-analysis was performed using random-effects modeling. The statistical heterogeneity among studies (I[2]-index), subgroup analyses and the possibility of publication bias were assessed.<br><br>RESULTS: Thirteen observational (11 cross-sectional/case-control and 2 longitudinal) studies involving a total of 81,162 middle-aged individuals of predominantly Asian ethnicity (47.5% of whom had H. pylori infection diagnosed by urea breath test, faecal or serological tests) were included in the final analysis. Meta-analysis of data from cross-sectional and case-control studies showed that H. pylori infection was associated with increased risk of prevalent NAFLD (n&#x202f;=&#x202f;11 studies; random-effects odds ratio [OR] 1.20, 95% CI 1.07-1.35; I[2]&#x202f;=&#x202f;59.6%); this risk remained significant in those studies where analysis was fully adjusted for age, sex, smoking, adiposity measures, diabetes or dyslipidemia (random-effects OR 1.19, 95% CI 1.07-1.32, I[2]&#x202f;=&#x202f;0%). Meta-analysis of data from longitudinal studies showed that H. pylori infection was also associated with increased NAFLD incidence (n&#x202f;=&#x202f;2 studies; random-effects hazard ratio 1.14, 95% CI 1.05-1.23; I[2]&#x202f;=&#x202f;0%). Sensitivity analyses did not alter these findings. Funnel plot did not reveal significant publication bias.<br><br>CONCLUSIONS: H. pylori infection is associated with mildly increased risk of both prevalent and incident NAFLD in middle-aged individuals. More prospective studies, particularly in non-Asian populations, and mechanistic studies are required to better elucidate the link between chronic H. pylori infection and NAFLD.}, }
@article {pmid31046972, year = {2019}, author = {Lavelle, A and Hill, C}, title = {Gut Microbiome in Health and Disease: Emerging Diagnostic Opportunities.}, journal = {Gastroenterology clinics of North America}, volume = {48}, number = {2}, pages = {221-235}, doi = {10.1016/j.gtc.2019.02.003}, pmid = {31046972}, issn = {1558-1942}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/therapeutic use ; Biomarkers ; Clinical Laboratory Techniques ; Clostridium Infections/diagnosis/drug therapy/microbiology ; Colorectal Neoplasms/*diagnosis/microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Immunotherapy ; Inflammatory Bowel Diseases/*diagnostic imaging/microbiology/therapy ; Mice ; Precision Medicine ; }, abstract = {The gut microbiome is fundamental to human health and development. Altered microbiomes have been associated with many diseases. However, variation between individuals, environmental effects, and a lack of standardization across studies makes differentiation between health and disease challenging. Large-scale population cohorts in different countries will be required to match disease subjects with healthy controls, whereas standardized, reproducible pipelines for analysis are required to compare findings between studies. Despite this, several conditions have already demonstrated great promise for developing microbiome-based biomarkers as well as providing a gateway into integrated personalized medicine.}, }
@article {pmid31044466, year = {2019}, author = {Adelstein, SA and Lee, W and Gioia, K and Moskowitz, D and Stamnes, K and Lucioni, A and Kobashi, KC and Lee, UJ}, title = {Outcomes in a contemporary cohort undergoing sacral neuromodulation using optimized lead placement technique.}, journal = {Neurourology and urodynamics}, volume = {38}, number = {6}, pages = {1595-1601}, doi = {10.1002/nau.24018}, pmid = {31044466}, issn = {1520-6777}, mesh = {Aged ; Electric Stimulation Therapy/*methods ; Fecal Incontinence/*therapy ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sacrum ; Treatment Outcome ; Urinary Bladder, Overactive/*therapy ; Urinary Retention/*therapy ; }, abstract = {AIMS: To evaluate factors associated with progression to stage 2 sacral neuromodulation (SNM) for refractory overactive bladder, urinary retention, or fecal incontinence using optimal lead placement techniques with curved stylet.<br><br>METHODS: This is a retrospective analysis of a prospectively collected database of all consecutive stage 1 SNM lead placements at our institution between August 2014 and May 2017 using optimal lead placement technique with curved stylet. Patients with refractory overactive bladder, urinary retention, or fecal incontinence were enrolled. Patients with 50% or more symptom improvement on voiding diaries were offered stage 2 implant. Demographics, clinical, and surgical characteristics were compared for patients who underwent successful stage 2 implants versus those who underwent lead removal at the end of the stage 1 trial period.<br><br>RESULTS: 127 patients underwent SNM during the study period. Motor thresholds of &#x2264;2&#x2009;mA in all four electrodes were achieved in 74% of patients (94/127). A total of 89.0% (113/127) of patients received stage 2 implants. The main indication for implant, specifically urgency urinary incontinence, was positively associated with progression to stage 2 implant. Male gender, history of pelvic pain and previous SNM were negatively associated with progression to stage 2 implant.<br><br>CONCLUSIONS: Our findings demonstrate that the contemporary optimized lead placement technique resulted in low motor thresholds and successful progression to stage 2 SNM implant in the majority of our cohort. Predictive factors associated with success or failure may potentially guide decision making for therapeutic interventions and counseling patient expectations.}, }
@article {pmid31041582, year = {2020}, author = {Lubomski, M and Tan, AH and Lim, SY and Holmes, AJ and Davis, RL and Sue, CM}, title = {Parkinson's disease and the gastrointestinal microbiome.}, journal = {Journal of neurology}, volume = {267}, number = {9}, pages = {2507-2523}, doi = {10.1007/s00415-019-09320-1}, pmid = {31041582}, issn = {1432-1459}, mesh = {*Enteric Nervous System ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; *Parkinson Disease/therapy ; alpha-Synuclein ; }, abstract = {Recently, there has been a surge in awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM and Parkinson's disease (PD) and the realisation that the GM can act via a complex bidirectional communication between the gut and the brain. Compelling evidence suggests that a shift in GM composition may play an important role in the pathogenesis of PD by facilitating the characteristic ascending neurodegenerative spread of α-synuclein aggregates from the enteric nervous system to the brain. Here, we review evidence linking GM changes with PD, highlighting mechanisms supportive of pathological α-synuclein spread and intestinal inflammation in PD. We summarise existing patterns and correlations seen in clinical studies of the GM in PD, together with the impacts of non-motor symptoms, medications, lifestyle, diet and ageing on the GM. Roles of GM modulating therapies including probiotics and faecal microbiota transplantation are discussed. Encouragingly, alterations in the GM have repeatedly been observed in PD, supporting a biological link and highlighting it as a potential therapeutic target.}, }
@article {pmid31040191, year = {2019}, author = {Wong, G and Hope, RL and Howard, K and Chapman, JR and Castells, A and Roger, SD and Bourke, MJ and Macaskill, P and Turner, R and Williams, G and Lim, WH and Lok, CE and Diekmann, F and Cross, NB and Sen, S and Allen, RDM and Chadban, SJ and Pollock, CA and Tong, A and Teixeira-Pinto, A and Yang, JYH and Williams, N and Au, EHK and Kieu, A and James, L and Craig, JC}, title = {One-Time Fecal Immunochemical Screening for Advanced Colorectal Neoplasia in Patients with CKD (DETECT Study).}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {30}, number = {6}, pages = {1061-1072}, pmid = {31040191}, issn = {1533-3450}, mesh = {Adult ; Aged ; Australia ; Canada ; *Cause of Death ; Cohort Studies ; Colonoscopy/methods ; Colorectal Neoplasms/diagnosis/*epidemiology/*pathology ; Comorbidity ; Early Detection of Cancer/*methods ; Female ; Humans ; Immunohistochemistry ; Internationality ; Male ; Mass Screening/methods ; Middle Aged ; New Zealand ; Occult Blood ; Prevalence ; Renal Insufficiency, Chronic/diagnosis/*epidemiology/*therapy ; Retrospective Studies ; Risk Assessment ; Spain ; Survival Analysis ; }, abstract = {BACKGROUND: In patients with CKD, the risk of developing colorectal cancer is high and outcomes are poor. Screening using fecal immunochemical testing (FIT) is effective in reducing mortality from colorectal cancer, but performance characteristics of FIT in CKD are unknown.<br><br>METHODS: To determine the detection rates and performance characteristics of FIT for advanced colorectal neoplasia (ACN) in patients with CKD, we used FIT to prospectively screen patients aged 35-74 years with CKD (stages 3-5 CKD, dialysis, and renal transplant) from 11 sites in Australia, New Zealand, Canada, and Spain. All participants received clinical follow-up at 2 years. We used a two-step reference standard approach to estimate disease status.<br><br>RESULTS: Overall, 369 out of 1706 patients who completed FIT (21.6%) tested positive; 323 (87.5%) underwent colonoscopies. A total of 1553 (91.0%) completed follow-up; 82 (4.8%) had died and 71 (4.2%) were lost. The detection rate of ACN using FIT was 6.0% (5.6%, 7.4%, and 5.6% for stages 3-5 CKD, dialysis, and transplant). Sensitivity, specificity, and positive and negative predictive values of FIT for ACN were 0.90, 0.83, 0.30, and 0.99, respectively. Of participants who underwent colonoscopy, five (1.5%) experienced major colonoscopy-related complications, including bowel perforation and major bleeding.<br><br>CONCLUSIONS: FIT appears to be an accurate screening test for patients with CKD, such that a negative test may rule out the diagnosis of colorectal cancer within 2 years. However, the risk of major complications from work-up colonoscopy are at least ten-fold higher than in the general population.}, }
@article {pmid31040040, year = {2019}, author = {Dukleska, K and Devin, CL and Martin, AE and Miller, JM and Sullivan, KM and Levy, C and Prestowitz, S and Flathers, K and Vinocur, CD and Berman, L}, title = {Necrotizing enterocolitis totalis: High mortality in the absence of an aggressive surgical approach.}, journal = {Surgery}, volume = {165}, number = {6}, pages = {1176-1181}, doi = {10.1016/j.surg.2019.03.005}, pmid = {31040040}, issn = {1532-7361}, mesh = {Conservative Treatment/mortality ; Digestive System Surgical Procedures/*methods/mortality ; Enterocolitis, Necrotizing/diagnosis/mortality/pathology/*surgery ; Humans ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/diagnosis/mortality/pathology/*surgery ; Treatment Outcome ; }, abstract = {BACKGROUND: Necrotizing enterocolitis is the leading case of gastrointestinal-related morbidity in premature infants. Necrotizing enterocolitis totalis is an aggressive form of necrotizing enterocolitis, which has traditionally been managed with comfort care. Recent advances in management of short bowel syndrome have resulted in some reported long-term survival.<br><br>METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies that reported outcomes in children with necrotizing enterocolitis totalis were identified. The definition of necrotizing enterocolitis totalis was captured along with length of follow-up, patient demographics, and outcomes.<br><br>RESULTS: A total of 766 articles were screened, of which 166 were selected for full article review. Of these, 32 articles included data on 414 patients with necrotizing enterocolitis totalis. In the majority of studies (52%), necrotizing enterocolitis totalis was not defined. Aggressive surgical therapy (defined as bowel resection or fecal diversion) was undertaken in 32 patients (7.7%), with a mortality rate of 68.8%. In contrast, nonaggressive surgical therapy was undertaken in 382 patients (92.3%), and the mortality in these patients was 95%. Long-term outcomes for necrotizing enterocolitis totalis survivors, such as length of time on parenteral nutrition, progression to liver and/or small bowel transplant, and quality of life, were not reported.<br><br>CONCLUSION: We found that there is no accepted definition of necrotizing enterocolitis totalis. Aggressive surgical therapy is rarely pursued, which likely drives the overall high mortality rate. This study underscores the importance of standardizing the definition of necrotizing enterocolitis totalis and capturing short and long-term outcomes prospectively. With more aggressive surgical therapy, more infants are likely to survive this abdominal catastrophe, which was once thought to be uniformly fatal.}, }
@article {pmid31038755, year = {2019}, author = {Bajaj, JS and Salzman, NH and Acharya, C and Sterling, RK and White, MB and Gavis, EA and Fagan, A and Hayward, M and Holtz, ML and Matherly, S and Lee, H and Osman, M and Siddiqui, MS and Fuchs, M and Puri, P and Sikaroodi, M and Gillevet, PM}, title = {Fecal Microbial Transplant Capsules Are Safe in Hepatic Encephalopathy: A Phase 1, Randomized, Placebo-Controlled Trial.}, journal = {Hepatology (Baltimore, Md.)}, volume = {70}, number = {5}, pages = {1690-1703}, pmid = {31038755}, issn = {1527-3350}, support = {UL1 TR002649/TR/NCATS NIH HHS/United States ; I0CX001076//Office of Research and Development/International ; I01 CX001076/CX/CSRD VA/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; }, mesh = {Administration, Oral ; Capsules ; *Fecal Microbiota Transplantation/methods ; Female ; Hepatic Encephalopathy/complications/*therapy ; Humans ; Liver Cirrhosis/complications ; Male ; Middle Aged ; Single-Blind Method ; }, abstract = {Hepatic encephalopathy (HE) can cause major morbidity despite standard of care (SOC; rifaximin/lactulose). Fecal microbial transplant (FMT) enemas postantibiotics are safe, but the effect of FMT without antibiotics using the capsular route requires investigation. The aim of this work was to determine the safety, tolerability, and impact on mucosal/stool microbiota and brain function in HE after capsular FMT in a randomized, single-blind, placebo-controlled clinical trial in Virginia. Patients with cirrhosis with recurrent HE with MELD (Model for End-Stage Liver Disease) <17 on SOC were randomized 1:1 into receiving 15 FMT capsules versus placebo from a single donor enriched in Lachnospiraceae and Ruminococcaceae. Endoscopies with duodenal and sigmoid biopsies, stool analysis, cognition, serum lipopolysaccharide-binding protein (LBP), and duodenal antimicrobial peptide (AMP) expression at baseline were used. Clinical follow-up with SOC maintenance was performed until 5 months. FMT-assigned patients underwent repeat endoscopies 4 weeks postenrollment. Twenty subjects on lactulose/rifaximin were randomized 1:1. MELD score was similar at baseline (9.6 vs. 10.2) and study end (10.2 vs. 10.5). Six patients in the placebo group required hospitalizations compared to 1 in FMT, which was deemed unrelated to FMT. Infection/HE episodes were similar between groups. Baseline microbial diversity was similar in all tissues between groups. Post-FMT, duodenal mucosal diversity (P = 0.01) increased with higher Ruminococcaceae and Bifidobacteriaceae and lower Streptococcaceae and Veillonellaceae. Reduction in Veillonellaceae were noted post-FMT in sigmoid (P = 0.04) and stool (P = 0.05). Duodenal E-cadherin (P = 0.03) and defensin alpha 5 (P = 0.03) increased whereas interleukin-6 (P = 0.02) and serum LBP (P = 0.009) reduced post-FMT. EncephalApp performance improved post-FMT only (P = 0.02). Conclusion: In this phase 1 study, oral FMT capsules are safe and well tolerated in patients with cirrhosis and recurrent HE. FMT was associated with improved duodenal mucosal diversity, dysbiosis, and AMP expression, reduced LBP, and improved EncephalApp performance. Further studies are needed to prove efficacy.}, }
@article {pmid31038368, year = {2019}, author = {Rodriguez-Palacios, A and Khoretonenko, MV and Ilic, S}, title = {Institutional protocols for the oral administration (gavage) of chemicals and microscopic microbial communities to mice: Analytical consensus.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {244}, number = {6}, pages = {459-470}, pmid = {31038368}, issn = {1535-3699}, support = {P01 DK091222/DK/NIDDK NIH HHS/United States ; R21 DK118373/DK/NIDDK NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Germ-Free Life ; Mice ; Microbiological Techniques/*standards ; *Microbiota ; *Models, Animal ; }, abstract = {Institutional protocols designed for the oral administration of live microbial communities, either complex or microscopic (microcosmic), to mice do not exist. However, this approach is increasingly employed by investigators focusing on the gut microbiome in experimental research. Herein, we propose two analytically Kappa-based consensus protocols to promote reproducibility and standardization in research practices and describe biologically relevant factors in achieving optimal microbial engraftment of communities in germ-free mice.}, }
@article {pmid31037552, year = {2019}, author = {Vujkovic-Cvijin, I and Somsouk, M}, title = {HIV and the Gut Microbiota: Composition, Consequences, and Avenues for Amelioration.}, journal = {Current HIV/AIDS reports}, volume = {16}, number = {3}, pages = {204-213}, pmid = {31037552}, issn = {1548-3576}, support = {Z99 AI999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Bacteria/*classification/*immunology ; Disease Progression ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; HIV Infections/*immunology ; Humans ; Inflammation/immunology ; }, abstract = {PURPOSE OF REVIEW: We discuss recent advances in understanding of gut bacterial microbiota composition in HIV-infected subjects and comment on controversies. We discuss the putative effects of microbiota shifts on systemic inflammation and HIV disease progression and potential mechanisms, as well as ongoing strategies being developed to modulate the gut microbiota in humans for amelioration of infectious and inflammatory diseases.<br><br>RECENT FINDINGS: Lifestyle and behavioral factors relevant to HIV infection studies have independent effects on the microbiota. Microbial metabolism of immunomodulatory compounds and direct immune stimulation by translocation of microbes are putative mechanisms contributing to HIV disease. Fecal microbiota transplantation, microbial enzyme inhibition, phage therapy, and rationally selected probiotic cocktails have emerged as promising strategies for microbiota modulation. Numerous surveys of the HIV gut microbiota matched for lifestyle factors suggest consistent shifts in gut microbiota composition among HIV-infected subjects. Evidence exists for a complex pathogenic role of the gut microbiota in HIV disease progression, warranting further study.}, }
@article {pmid31037294, year = {2019}, author = {Chadchan, SB and Cheng, M and Parnell, LA and Yin, Y and Schriefer, A and Mysorekar, IU and Kommagani, R}, title = {Antibiotic therapy with metronidazole reduces endometriosis disease progression in mice: a potential role for gut microbiota.}, journal = {Human reproduction (Oxford, England)}, volume = {34}, number = {6}, pages = {1106-1116}, pmid = {31037294}, issn = {1460-2350}, support = {R25 GM103757/GM/NIGMS NIH HHS/United States ; P30 CA091842/CA/NCI NIH HHS/United States ; R00 HD080742/HD/NICHD NIH HHS/United States ; K99 HD080742/HD/NICHD NIH HHS/United States ; R01 HD091218/HD/NICHD NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*administration &amp; dosage ; Disease Models, Animal ; Disease Progression ; Endometriosis/*drug therapy/microbiology/pathology ; Endometrium/pathology ; Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Metronidazole/*administration &amp; dosage ; Mice ; Peritoneal Diseases/*drug therapy/microbiology/pathology ; }, abstract = {STUDY QUESTION: Does altering gut microbiota with antibiotic treatment have any impact on endometriosis progression?<br><br>SUMMARY ANSWER: Antibiotic therapy reduces endometriosis progression in mice, possibly by reducing specific gut bacteria.<br><br>WHAT IS KNOWN ALREADY: Endometriosis, a chronic condition causing abdominal pain and infertility, afflicts up to 10% of women between the ages of 25 and 40, ~5 million women in the USA. Current treatment strategies, including hormone therapy and surgery, have significant side effects and do not prevent recurrences. We have little understanding of why some women develop endometriosis and others do not.<br><br>STUDY DESIGN, SIZE, DURATION: Mice were treated with broad-spectrum antibiotics or metronidazole, subjected to surgically-induced endometriosis and assayed after 21 days.<br><br>The volumes and weights of endometriotic lesions and histological signatures were analysed. Proliferation and inflammation in lesions were assessed by counting cells that were positive for the proliferation marker Ki-67 and the macrophage marker Iba1, respectively. Differences in faecal bacterial composition were assessed in mice with and without endometriosis, and faecal microbiota transfer studies were performed.<br><br>In mice treated with broad-spectrum antibiotics (vancomycin, neomycin, metronidazole and ampicillin), endometriotic lesions were significantly smaller (~ 5-fold; P < 0.01) with fewer proliferating cells (P < 0.001) than those in mice treated with vehicle. Additionally, inflammatory responses, as measured by the macrophage marker Iba1 in lesions and IL-1&#x3b2;, TNF-&#x3b1;, IL-6 and TGF-&#x3b2;1 in peritoneal fluid, were significantly reduced in mice treated with broad-spectrum antibiotics (P < 0.05). In mice treated with metronidazole only, but not in those treated with neomycin, ectopic lesions were significantly (P < 0.001) smaller in volume than those from vehicle-treated mice. Finally, oral gavage of faeces from mice with endometriosis restored the endometriotic lesion growth and inflammation (P < 0.05 and P < 0.01, respectively) in metronidazole-treated mice.<br><br>LARGE-SCALE DATA: N/A.<br><br>These findings are from a mouse model of surgically-induced endometriosis. Further studies are needed to determine the mechanism by which gut bacteria promote inflammation, identify bacterial genera or species that promote disease progression and assess the translatability of these findings to humans.<br><br>Our findings suggest that gut bacteria promote endometriosis progression in mice. This finding if translated to humans, could aid in the development of improved diagnostic tools and personalised treatment strategies.<br><br>This work was funded, in part, by: a National Institutes of Health (NIH)/ National Institute of Child Health and Human Development (NICHD) grant (R00HD080742) to RK; Washington University School of Medicine start-up funds to RK; an Endometriosis Foundation of America Research Award to R.K.; and an NIH/NICHD grant (R01HD091218) to IUM. The authors report no conflict of interest.}, }
@article {pmid31036757, year = {2020}, author = {Torres, J and Hu, J and Seki, A and Eisele, C and Nair, N and Huang, R and Tarassishin, L and Jharap, B and Cote-Daigneault, J and Mao, Q and Mogno, I and Britton, GJ and Uzzan, M and Chen, CL and Kornbluth, A and George, J and Legnani, P and Maser, E and Loudon, H and Stone, J and Dubinsky, M and Faith, JJ and Clemente, JC and Mehandru, S and Colombel, JF and Peter, I}, title = {Infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice.}, journal = {Gut}, volume = {69}, number = {1}, pages = {42-51}, doi = {10.1136/gutjnl-2018-317855}, pmid = {31036757}, issn = {1468-3288}, support = {P01 DK072201/DK/NIDDK NIH HHS/United States ; S10 OD018522/OD/NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Adult ; Animals ; Bacteria/classification/isolation &amp; purification ; Dysbiosis/immunology/microbiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/*immunology ; Gastrointestinal Tract/immunology/microbiology ; Germ-Free Life ; Humans ; Infant, Newborn ; Inflammatory Bowel Diseases/immunology/*microbiology ; Male ; Maternal-Fetal Exchange ; Pregnancy ; Pregnancy Complications/immunology/*microbiology ; Prenatal Exposure Delayed Effects/immunology/*microbiology ; Prospective Studies ; }, abstract = {BACKGROUND AND AIMS: Prenatal and early life bacterial colonisation is thought to play a major role in shaping the immune system. Furthermore, accumulating evidence links early life exposures to the risk of developing IBD later in life. We aimed to assess the effect of maternal IBD on the composition of the microbiome during pregnancy and on the offspring's microbiome.<br><br>METHODS: We prospectively examined the diversity and taxonomy of the microbiome of pregnant women with and without IBD and their babies at multiple time points. We evaluated the role of maternal IBD diagnosis, the mode of delivery, antibiotic use and feeding behaviour on the microbiome composition during early life. To assess the effects of IBD-associated maternal and infant microbiota on the enteric immune system, we inoculated germ-free mice (GFM) with the respective stool and profiled adaptive and innate immune cell populations in the murine intestines.<br><br>RESULTS: Pregnant women with IBD and their offspring presented with lower bacterial diversity and altered bacterial composition compared with control women and their babies. Maternal IBD was the main predictor of the microbiota diversity in the infant gut at 7, 14, 30, 60 and 90 days of life. Babies born to mothers with IBD demonstrated enrichment in Gammaproteobacteria and depletion in Bifidobacteria. Finally, GFM inoculated with third trimester IBD mother and 90-day infant stools showed significantly reduced microbial diversity and fewer class-switched memory B cells and regulatory T cells in the colon.<br><br>CONCLUSION: Aberrant gut microbiota composition persists during pregnancy with IBD and alters the bacterial diversity and abundance in the infant stool. The dysbiotic microbiota triggered abnormal imprinting of the intestinal immune system in GFM.}, }
@article {pmid31028919, year = {2019}, author = {Posovszky, C and Sirin, M and Jacobsen, E and Lorenz, M and Schwarz, K and Schmidt-Choudhury, A and Rothoeft, T and Schuetz, C and Hönig, M and Debatin, KM and Schulz, A and Möller, P and Barth, TF}, title = {Persisting enteropathy and disturbed adaptive mucosal immunity due to MHC class II deficiency.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {203}, number = {}, pages = {125-133}, doi = {10.1016/j.clim.2019.04.012}, pmid = {31028919}, issn = {1521-7035}, mesh = {Adaptive Immunity ; Adolescent ; Child ; Child, Preschool ; DNA Mutational Analysis ; DNA-Binding Proteins/genetics ; Female ; Gastrointestinal Diseases/genetics/*immunology ; HLA-DR Antigens/*genetics/metabolism ; Humans ; Immunologic Deficiency Syndromes/genetics/*immunology ; Infant ; Inflammation/genetics/*immunology ; Intestinal Mucosa/*immunology ; Male ; Mutation/genetics ; Pedigree ; Transcription Factors/genetics ; }, abstract = {Intestinal epithelial cells (IECs) form a fundamental mucosal barrier and actively participate in tolerance and immunity against intestinal contents. Major histocompatibility complex class II (MHC II) and invariant chain (Ii) molecules are essential for adaptive immune response. MHC II deficiency often presents with gastrointestinal disorders. Intestinal biopsy samples revealed an absence of HLA-DR, Ii, and local immunoglobulins in both hematopoietic immune cells and IECs accompanied by a lack of faecal sIgA. After successful hematopoietic stem cell transplantation (HSCT) absent HLA-DR and Ii expression persisted in IECs and faecal stool analysis indicated inflammation and high microbial activity. We describe multifaceted disturbance of adaptive mucosal immunity in MHC II deficient patients suffering from enteropathy. HLA-DR and Ii expression on enterocytes is not restored by HSCT. This may account for increased susceptibility to enteric infections and intestinal inflammation leading to prolonged enteropathy reported in MHC II deficient patients.}, }
@article {pmid31028093, year = {2019}, author = {Jimenez, M and Langer, R and Traverso, G}, title = {Microbial therapeutics: New opportunities for drug delivery.}, journal = {The Journal of experimental medicine}, volume = {216}, number = {5}, pages = {1005-1009}, pmid = {31028093}, issn = {1540-9538}, mesh = {Bifidobacterium ; Clostridium ; Clostridium Infections/microbiology/*therapy ; Drug Compounding ; *Drug Delivery Systems ; Drug Dosage Calculations ; Escherichia coli ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Humans ; *Vaccines, Live, Unattenuated ; }, abstract = {With >40 clinical trials underway, we are nearing the first FDA-approved live microbial therapeutic. Here, Giovanni Traverso, MIT and Harvard Medical School Assistant Professor, and colleagues Miguel Jimenez and Institute Professor Robert Langer from MIT discuss the significant challenges of administering live microorganisms to patients and the opportunities for drug delivery of these new complex therapeutics.}, }
@article {pmid31023615, year = {2019}, author = {Piñero, F and Vazquez, M and Baré, P and Rohr, C and Mendizabal, M and Sciara, M and Alonso, C and Fay, F and Silva, M}, title = {A different gut microbiome linked to inflammation found in cirrhotic patients with and without hepatocellular carcinoma.}, journal = {Annals of hepatology}, volume = {18}, number = {3}, pages = {480-487}, doi = {10.1016/j.aohep.2018.10.003}, pmid = {31023615}, issn = {1665-2681}, mesh = {Carcinoma, Hepatocellular/complications/diagnosis/*microbiology ; Case-Control Studies ; Cytokines/*metabolism ; Feces/microbiology ; Female ; Follow-Up Studies ; *Gastrointestinal Microbiome ; Humans ; Inflammation/diagnosis/metabolism/*microbiology ; Liver Cirrhosis/complications/diagnosis/*microbiology ; Liver Neoplasms/complications/diagnosis/*microbiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Prospective Studies ; Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION AND AIM: A pro-oncogenic intestinal microbiome was observed in murine models; however, no specific microbiome in patients with hepatocellular carcinoma (HCC) has been reported. We aimed to compare the gut microbiome found in cirrhotic patients with or without HCC.<br><br>MATERIALS AND METHODS: From 407 patients with Child Pugh A/B cirrhosis prospectively followed, 25 with HCC (cases) were matched with 25 without HCC (wo-HCC) in a 1:1 ratio according to age, gender, etiology, Child Pugh and severity of portal hypertension. In addition, results were also compared with 25 healthy subjects. Fecal stool samples were sequenced for the V3-V4 region of the microbial 16S rRNA (Illumina MiSeq Platform). Plasma cytokines were quantified including interleukin-6 (IL-6) and tumor necrosis factor &#x3b1; (TNF-&#x3b1;).<br><br>RESULTS: We found a differential abundance in family members of Firmicutes with a 3-fold increase of Erysipelotrichaceae and a 5-fold decrease in family Leuconostocaceae in HCC when compared to wo-HCC controls. Genus Fusobacterium was found to be 5-fold decreased in HCC vs wo-HCC. The ratio bacteriodes/prevotella was increased in HCC. Three operational taxonomic units (OTUs), genus Odoribacter and Butyricimonas were more abundant in HCC, whereas a decreased abundance in Lachnospiraceae family genus Dorea was observed in HCC patients. A Random Forest model trained with differential abundant taxa correctly classified HCC individuals. This pattern was associated with an inflammatory milieu with a putative increased activation of NOD-like receptor pathways.<br><br>CONCLUSION: We found a pattern of microbiome linked to inflammation that could be potentially useful as HCC biomarker after follow-up validation studies.}, }
@article {pmid31019401, year = {2019}, author = {Campbell, CT and Poisson, MO and Hand, EO}, title = {An Updated Review of Clostridium difficile Treatment in Pediatrics.}, journal = {The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG}, volume = {24}, number = {2}, pages = {90-98}, pmid = {31019401}, issn = {1551-6776}, abstract = {Clostridium difficile infection (CDI) continues to have clinical and economic impact across all health care settings. Pediatrics accounts for a small percentage of worldwide infection; however, screening and diagnosis are confounded by asymptomatic colonization in young infants. Metronidazole and oral vancomycin have historically been the agents used to manage CDI in both pediatrics and adults. Newer agents and alternative therapies, such as fecal microbiota transplantation, may offer additional benefit. Recent guidelines updates from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America separate pediatric and adult recommendations for epidemiology, diagnosis, and treatment. This review will discuss the risk factors, management, prevention, and updated guideline recommendations for CDI in the pediatric population.}, }
@article {pmid31017741, year = {2019}, author = {Hsu, WH and Wang, JY and Kuo, CH}, title = {Current applications of fecal microbiota transplantation in intestinal disorders.}, journal = {The Kaohsiung journal of medical sciences}, volume = {35}, number = {6}, pages = {327-331}, doi = {10.1002/kjm2.12069}, pmid = {31017741}, issn = {2410-8650}, support = {KMUH103-3M02//Kaohsiung Medical University Hospital, Taiwan/ ; MOHW107-TDU-B-212-113006//Ministry of Health and Welfare/ ; MOST108-2321-B-037-001//Ministry of Science and Technology/ ; }, mesh = {Administration, Oral ; Administration, Rectal ; Clostridioides difficile/pathogenicity/physiology ; Clostridium Infections/microbiology/pathology/*therapy ; Constipation/etiology/physiopathology ; Diarrhea/etiology/physiopathology ; Enema/methods ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Fever/etiology/physiopathology ; Flatulence/etiology/physiopathology ; Gastrointestinal Microbiome/physiology ; Humans ; Inflammatory Bowel Diseases/microbiology/pathology/*therapy ; Randomized Controlled Trials as Topic ; Vomiting/etiology/physiopathology ; }, abstract = {Fecal microbiota transplantation (FMT) had been an ancient remedy for severe illness several centuries ago. Under modern medical analysis and evidence-based research, it has been proved as an alternative treatment for recurrent Clostridium difficile infection and recent randomized control study also showed that FMT could be an adjuvant treatment for inflammatory bowel disease. As we get a better understanding of the relationship between gut microbiota and systemic disease, FMT became a potential treatment to explore. This article summarized procedures such as donor selection, fecal material preparation, transplantation delivery methods, and adverse events. We also review the present evidence about FMT in clinical practice.}, }
@article {pmid31010813, year = {2019}, author = {Dubin, KA and Mathur, D and McKenney, PT and Taylor, BP and Littmann, ER and Peled, JU and van den Brink, MRM and Taur, Y and Pamer, EG and Xavier, JB}, title = {Diversification and Evolution of Vancomycin-Resistant Enterococcus faecium during Intestinal Domination.}, journal = {Infection and immunity}, volume = {87}, number = {7}, pages = {}, pmid = {31010813}, issn = {1098-5522}, support = {R01 CA228308/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; DNA Mutational Analysis ; DNA, Bacterial/*genetics ; Enterococcus faecium/*genetics ; Feces/microbiology ; *Genetic Variation ; Gram-Positive Bacterial Infections/*microbiology ; Humans ; Longitudinal Studies ; RNA, Ribosomal, 16S/genetics ; Vancomycin-Resistant Enterococci/*genetics ; }, abstract = {Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. This is particularly true in immunocompromised patients, where the damage to the microbiota caused by antibiotics can lead to VRE domination of the intestine, increasing a patient's risk for bloodstream infection. In previous studies we observed that the intestinal domination by VRE of patients hospitalized to receive allogeneic bone marrow transplantation can persist for weeks, but little is known about subspecies diversification and evolution during prolonged domination. Here we combined a longitudinal analysis of patient data and in vivo experiments to reveal previously unappreciated subspecies dynamics during VRE domination that appeared to be stable from 16S rRNA microbiota analyses. Whole-genome sequencing of isolates obtained from sequential stool samples provided by VRE-dominated patients revealed an unanticipated level of VRE population complexity that evolved over time. In experiments with ampicillin-treated mice colonized with a single CFU, VRE rapidly diversified and expanded into distinct lineages that competed for dominance. Mathematical modeling shows that in vivo evolution follows mostly a parabolic fitness landscape, where each new mutation provides diminishing returns and, in the setting of continuous ampicillin treatment, reveals a fitness advantage for mutations in penicillin-binding protein 5 (pbp5) that increase resistance to ampicillin. Our results reveal the rapid diversification of host-colonizing VRE populations, with implications for epidemiologic tracking of in-hospital VRE transmission and susceptibility to antibiotic treatment.}, }
@article {pmid31009795, year = {2020}, author = {Nicholson, MR and Mitchell, PD and Alexander, E and Ballal, S and Bartlett, M and Becker, P and Davidovics, Z and Docktor, M and Dole, M and Felix, G and Gisser, J and Hourigan, SK and Jensen, MK and Kaplan, JL and Kelsen, J and Kennedy, M and Khanna, S and Knackstedt, E and Leier, M and Lewis, J and Lodarek, A and Michail, S and Oliva-Hemker, M and Patton, T and Queliza, K and Russell, GH and Singh, N and Solomon, A and Suskind, DL and Werlin, S and Kellermayer, R and Kahn, SA}, title = {Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {18}, number = {3}, pages = {612-619.e1}, pmid = {31009795}, issn = {1542-7714}, support = {UL1 TR000445/TR/NCATS NIH HHS/United States ; KL2 TR002245/TR/NCATS NIH HHS/United States ; L30 AI140315/AI/NIAID NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; }, mesh = {Child ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Feces ; Humans ; Recurrence ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI.<br><br>METHODS: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT.<br><br>RESULTS: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations.<br><br>CONCLUSIONS: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients.}, }
@article {pmid31009405, year = {2019}, author = {Holster, S and Lindqvist, CM and Repsilber, D and Salonen, A and de Vos, WM and König, J and Brummer, RJ}, title = {The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study.}, journal = {Clinical and translational gastroenterology}, volume = {10}, number = {4}, pages = {e00034}, pmid = {31009405}, issn = {2155-384X}, mesh = {Adult ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; Humans ; Irritable Bowel Syndrome/complications/immunology/microbiology/*therapy ; Male ; Middle Aged ; Pain Measurement ; Transplantation, Autologous/methods ; Transplantation, Homologous/methods ; Treatment Outcome ; Visceral Pain/diagnosis/etiology/*therapy ; }, abstract = {OBJECTIVES: Fecal microbiota transfer (FMT) is suggested as a potential treatment for patients with irritable bowel syndrome (IBS). We aimed to study the effect of allogenic and autologous FMT on IBS symptoms, visceral sensitivity, and compositional changes in fecal and mucosa-adherent microbiota.<br><br>METHODS: Seventeen patients with IBS were randomized either to receive fecal material from a healthy donor (allogenic) or to receive their own fecal material (autologous). The fecal material was administered into the cecum by whole colonoscopy after bowel cleansing.<br><br>RESULTS: No significant differences were found between the allogenic and the autologous FMT regarding symptom scores. However, symptom scores of patients receiving allogenic fecal material significantly decreased after FMT compared with baseline (P = 0.02), which was not the case in the autologous group (P = 0.16). Visceral sensitivity was not affected except for a small beneficial effect on urge scores in the autologous group (P < 0.05). While both fecal and mucosa-adherent microbiota of some patients shifted to their respective donor's fecal microbiota, some patients showed no relevant microbial changes after allogenic FMT. Large compositional shifts in fecal and mucosa-adherent microbiota also occurred in the autologous group.<br><br>CONCLUSIONS: This study showed that a single FMT by colonoscopy may have beneficial effects in IBS; however, the allogenic fecal material was not superior to the autologous fecal material. This suggests that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.}, }
@article {pmid31007720, year = {2019}, author = {Dehlholm-Lambertsen, E and Hall, BK and Jørgensen, SMD and Jørgensen, CW and Jensen, ME and Larsen, S and Jensen, JS and Ehlers, L and Dahlerup, JF and Hvas, CL}, title = {Cost savings following faecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {12}, number = {}, pages = {1756284819843002}, pmid = {31007720}, issn = {1756-283X}, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (rCDI) is becoming increasingly common. Faecal microbiota transplantation (FMT) is effective for rCDI, but the costs of an FMT and hospital cost savings related to FMT are unknown. The aim of this study was to calculate the cost of an FMT and the total hospital costs before and after FMT.<br><br>METHODS: This was an observational single-centre study, carried out in a public teaching hospital. We included all patients referred for rCDI from January 2014 through December 2015 and documented costs related to donor screening, laboratory processing, and clinical FMT application. We calculated patient-related hospital costs 1 year before FMT (pre-FMT) and 1 year after FMT (post-FMT). Sensitivity analyses were applied to assess the robustness of the results.<br><br>RESULTS: We included 50 consecutive adult patients who had a verified diagnosis of rCDI and were referred for FMT. The average cost of an outpatient FMT procedure if donor faeces were applied by colonoscopy was &#x20ac;3,326&#x2009;per patient and &#x20ac;2,864 if donor faeces were applied using a nasojejunal tube. The total annual pre-FMT hospital costs per patient were &#x20ac;56,415 (95% confidence interval (CI) 41,133-71,697), and these costs dropped by 42% to &#x20ac;32,816 (22,618-42,014) post-FMT (p = 0.004). The main cost driver was hospital admissions. Sensitivity analyses demonstrated cost reductions in all scenarios.<br><br>CONCLUSIONS: In a public hospital with an implemented FMT service, the average cost of FMT applied by either colonoscopy or nasojejunal tube was &#x20ac;3,095. Total hospital costs dropped by 42% the first year after FMT. The reduction was mainly caused by reductions in the number of hospital admissions and in length of stay.}, }
@article {pmid31005929, year = {2019}, author = {Leong, KSW and Jayasinghe, TN and Derraik, JGB and Albert, BB and Chiavaroli, V and Svirskis, DM and Beck, KL and Conlon, CA and Jiang, Y and Schierding, W and Vatanen, T and Holland, DJ and O'Sullivan, JM and Cutfield, WS}, title = {Protocol for the Gut Bugs Trial: a randomised double-blind placebo-controlled trial of gut microbiome transfer for the treatment of obesity in adolescents.}, journal = {BMJ open}, volume = {9}, number = {4}, pages = {e026174}, pmid = {31005929}, issn = {2044-6055}, mesh = {Adolescent ; Adult ; Body Mass Index ; Double-Blind Method ; Dysbiosis/etiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Follow-Up Studies ; *Gastrointestinal Microbiome ; Humans ; Male ; Pediatric Obesity/complications/*therapy ; Quality of Life ; Treatment Outcome ; Young Adult ; }, abstract = {INTRODUCTION: Animal studies showed that germ-free mice inoculated with normal mouse gut bacteria developed obesity, insulin resistance and higher triglyceride levels, despite similar food intake. In humans, an association has been found between obesity and gut microbiome dysbiosis. However, gut microbiome transfer has not been evaluated for the treatment of human obesity. We will examine the effectiveness of gut microbiome transfer using encapsulated material for the treatment of obesity in adolescents.<br><br>METHODS AND ANALYSIS: A two-arm, double-blind, placebo-controlled, randomised clinical trial of a single course of gut microbiome transfer will be conducted in 80 obese [body mass index (BMI) &#x2265;30&#x2009;kg/m[2]] adolescents (males and females, aged 14-18 years) in Auckland, New Zealand. Healthy lean donors (males and females, aged 18-28 years) will provide fresh stool samples from which bacteria will be isolated and double encapsulated. Participants (recipients) will be randomised at 1:1 to control (placebo) or treatment (gut microbiome transfer), stratified by sex. Recipients will receive 28 capsules over two consecutive mornings (~14&#x2009;mL of frozen microbial suspension or saline). Clinical assessments will be performed at baseline, 6, 12 and 26 weeks, and will include: anthropometry, blood pressure, fasting metabolic markers, dietary intake, physical activity levels and health-related quality of life. Insulin sensitivity (Matsuda index), gut microbiota population structure characterised by 16S rRNA amplicon sequencing and body composition (using dual-energy X-ray absorptiometry) will be assessed at baseline, 6, 12 and 26 weeks. 24-hour ambulatory blood pressure monitoring will be performed at baseline and at 6 weeks. The primary outcome is BMI SD scores (SDS) at 6 weeks, with BMI SDS at 12 and 26 weeks as secondary outcomes. Other secondary outcomes include insulin sensitivity, adiposity (total body fat percentage) and gut microbial composition at 6, 12 and 26 weeks. Statistical analysis will be performed on the principle of intention to treat.<br><br>ETHICS AND DISSEMINATION: Ethics approval was provided by the Northern A Health and Disability Ethics Committee (Ministry of Health, New Zealand; 16/NTA/172). The trial results will be published in peer-reviewed journals and presented at international conferences.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12615001351505; Pre-results.}, }
@article {pmid31005136, year = {2019}, author = {Misch, EA and Safdar, N}, title = {Clostridioides difficile Infection in the Stem Cell Transplant and Hematologic Malignancy Population.}, journal = {Infectious disease clinics of North America}, volume = {33}, number = {2}, pages = {447-466}, pmid = {31005136}, issn = {1557-9824}, support = {DP2 AI144244/AI/NIAID NIH HHS/United States ; R01 HS025713/HS/AHRQ HHS/United States ; R01 HS026226/HS/AHRQ HHS/United States ; U01 AI125053/AI/NIAID NIH HHS/United States ; }, mesh = {Clostridioides difficile ; Clostridium Infections/*therapy ; Drug Therapy ; Fecal Microbiota Transplantation ; Feces/microbiology ; Graft vs Host Disease/complications/microbiology ; Hematologic Neoplasms/complications/*microbiology ; Humans ; Microbiota ; Randomized Controlled Trials as Topic ; Risk Factors ; Stem Cell Transplantation/*adverse effects ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection (CDI) is common in the stem cell transplant (SCT) and hematologic malignancy (HM) population and mostly occurs in the early posttransplant period. Treatment of CDI in SCT/HM is the same as for the general population, with the exception that fecal microbiota transplant (FMT) has not been widely adopted because of safety concerns. Several case reports, small series, and retrospective studies have shown that FMT is effective and safe. A randomized controlled trial of FMT for prophylaxis of CDI in SCT patients is underway. In addition, an abundance of novel therapeutics for CDI is currently in development.}, }
@article {pmid31004524, year = {2019}, author = {Xie, Y and Matsumoto, H and Kennedy, S and Newberry, EP and Moritz, W and DeBosch, BJ and Moley, KH and Rubin, DC and Warner, BW and Kau, AL and Tarr, PI and Wylie, TN and Wylie, KM and Davidson, NO}, title = {Impaired Chylomicron Assembly Modifies Hepatic Metabolism Through Bile Acid-Dependent and Transmissible Microbial Adaptations.}, journal = {Hepatology (Baltimore, Md.)}, volume = {70}, number = {4}, pages = {1168-1184}, pmid = {31004524}, issn = {1527-3350}, support = {R01 DK106382/DK/NIDDK NIH HHS/United States ; R01 HD083895/HD/NICHD NIH HHS/United States ; P30 DK056341/DK/NIDDK NIH HHS/United States ; R01 DK112378/DK/NIDDK NIH HHS/United States ; R01 HD065435/HD/NICHD NIH HHS/United States ; R01 DK119437/DK/NIDDK NIH HHS/United States ; R01 HL038180/HL/NHLBI NIH HHS/United States ; //Robert Wood Johnson Foundation/International ; R37 HL038180/HL/NHLBI NIH HHS/United States ; P30 DK020579/DK/NIDDK NIH HHS/United States ; //Manpei Suzuki Diabetes Foundation/International ; R01 DK056260/DK/NIDDK NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; K08 AI113184/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; Akkermansia ; Animals ; Bile Acids and Salts/metabolism ; Biological Transport/genetics ; Carrier Proteins/metabolism ; Chylomicrons/*genetics ; Disease Models, Animal ; Fatty Liver/*metabolism/pathology ; Fructose/pharmacology ; Gastrointestinal Microbiome/*genetics ; Glucose Tolerance Test ; Humans ; Intestinal Mucosa/metabolism ; Lipid Metabolism/*genetics ; Mice ; Mice, Inbred C57BL ; Random Allocation ; Sensitivity and Specificity ; Signal Transduction ; Verrucomicrobia/pathogenicity ; }, abstract = {The mechanisms by which alterations in intestinal bile acid (BA) metabolism improve systemic glucose tolerance and hepatic metabolic homeostasis are incompletely understood. We examined metabolic adaptations in mice with conditional intestinal deletion of the abetalipoproteinemia (ABL) gene microsomal triglyceride transfer protein (Mttp-IKO), which blocks chylomicron assembly and impairs intestinal lipid transport. Mttp-IKO mice exhibit improved hepatic glucose metabolism and augmented insulin signaling, without weight loss. These adaptations included decreased BA excretion, increased pool size, altered BA composition, and increased fibroblast growth factor 15 production. Mttp-IKO mice absorb fructose normally but are protected against dietary fructose-induced hepatic steatosis, without weight loss or changes in energy expenditure. In addition, Mttp-IKO mice exhibit altered cecal microbial communities, both at baseline and following fructose feeding, including increased abundance of Bacteroides and Lactobacillus genera. Transplantation of cecal microbiota from chow-fed Mttp-IKO mice into antibiotic-treated wild-type recipients conferred transmissible protection against fructose-induced hepatic steatosis in association with a bloom in Akkermansia and increased Clostridium XIVa genera, whose abundance was positively correlated with fecal coprostanol and total neutral sterol excretion in recipient mice. However, antibiotic-treated Mttp-IKO mice were still protected against fructose-induced hepatic steatosis, suggesting that changes in microbiota are not required for this phenotype. Nevertheless, we found increased abundance of fecal Akkermansia from two adult ABL subjects with MTTP mutations compared to their heterozygous parents and within the range noted in six healthy control subjects. Furthermore, Akkermansia abundance across all subjects was positively correlated with fecal coprostanol excretion. Conclusion: The findings collectively suggest multiple adaptive pathways of metabolic regulation following blocked chylomicron assembly, including shifts in BA signaling and altered microbial composition that confer a transmissible phenotype.}, }
@article {pmid31004464, year = {2019}, author = {Toral, M and Robles-Vera, I and de la Visitación, N and Romero, M and Sánchez, M and Gómez-Guzmán, M and Rodriguez-Nogales, A and Yang, T and Jiménez, R and Algieri, F and Gálvez, J and Raizada, MK and Duarte, J}, title = {Role of the immune system in vascular function and blood pressure control induced by faecal microbiota transplantation in rats.}, journal = {Acta physiologica (Oxford, England)}, volume = {227}, number = {1}, pages = {e13285}, doi = {10.1111/apha.13285}, pmid = {31004464}, issn = {1748-1716}, support = {//FEDER funds/International ; SAF2017-84894-R//Ministerio de Econom&#xed;a y competitividad/International ; SAF2014-55523-R//Ministerio de Econom&#xed;a y competitividad/International ; AGL2015-67995-C3//Ministerio de Econom&#xed;a y competitividad/International ; Proyecto de excelencia P12-CTS-2722//Junta de Andaluc&#xed;a/International ; AGR-6826//Junta de Andaluc&#xed;a/International ; //Comisi&#xf3;n Interministerial de Ciencia y Tecnolog&#xed;a/International ; //Instituto de Salud Carlos III/International ; //University of Granada/International ; }, mesh = {Animals ; Blood Pressure ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gene Expression Regulation/*immunology ; Hypertension/*prevention &amp; control ; Lymph Nodes/cytology ; Mesentery ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; }, abstract = {AIM: High blood pressure (BP) is associated with gut microbiota dysbiosis. The aim of this study was to investigate whether changes in gut microbiota induced by exchanging the gut microbiota between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) alter the gut-immune system interaction inducing changes in vascular function and BP.<br><br>METHODS: Twenty-week-old recipient WKY and SHR were orally gavaged with donor faecal contents from WKY or SHR. In additional experiments, we used a design to determine whether blockade of B7-dependent costimulation with CTLA4-Ig or blockade of IL-17 with IL-17-neutralizing antibody could prevent hypertension caused by faecal microbiota transplantation (FMT) from SHR to WKY.<br><br>RESULTS: Correlation analyses identified the bacterial abundance of Turicibacter and S24-7_g that, respectively, positively and negatively correlated with systolic BP. FMT from WKY rats to SHR rats reduced basal systolic BP, restored the imbalance between Th17/Treg in mesenteric lymph nodes (MLNs) and aorta, and improved endothelial dysfunction and vascular oxidative status found in SHR transplanted with SHR faeces. FMT from SHR to WKY increased CD80 and CD86 mRNA levels and T cells activation in MLNs, circulating T cells, aortic T cell infiltration, impaired endothelial function and increased basal SBP. These effects were abolished by blockade of B7-dependent costimulation with CTLA4-Ig. IL-17a neutralizing antibody reduced SBP and improved endothelial dysfunction induced by FMT from SHR to WKY.<br><br>CONCLUSION: Gut microbiota is an important factor involved in the control of BP, as a consequence of its effect in T-cell activation in gut immune system and vascular T-cells accumulation.}, }
@article {pmid31001619, year = {2020}, author = {Rajasingham, R and Enns, EA and Khoruts, A and Vaughn, BP}, title = {Cost-effectiveness of Treatment Regimens for Clostridioides difficile Infection: An Evaluation of the 2018 Infectious Diseases Society of America Guidelines.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {70}, number = {5}, pages = {754-762}, pmid = {31001619}, issn = {1537-6591}, support = {K23 AI138851/AI/NIAID NIH HHS/United States ; K25 AI118476/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/drug therapy ; *Communicable Diseases/drug therapy ; Cost-Benefit Analysis ; Humans ; Recurrence ; }, abstract = {BACKGROUND: In 2018, the Infectious Diseases Society of America (IDSA) published guidelines for diagnosis and treatment of Clostridioides (formerly Clostridium) difficile infection (CDI). However, there is little guidance regarding which treatments are cost-effective.<br><br>METHODS: We used a Markov model to simulate a cohort of patients presenting with an initial CDI diagnosis. We used the model to estimate the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the recently published 2018 IDSA guidelines. The model includes stratification by the severity of the initial infection, and subsequent likelihood of cure, recurrence, mortality, and outcomes of subsequent recurrences. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).<br><br>RESULTS: Use of fidaxomicin for nonsevere initial CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and fecal microbiota transplantation (FMT) for subsequent recurrence (strategy 44) cost an additional $478 for 0.009 QALYs gained per CDI patient, resulting in an ICER of $31 751 per QALY, below the willingness-to-pay threshold of $100 000/QALY. This is the optimal, cost-effective CDI treatment strategy.<br><br>CONCLUSIONS: Metronidazole is suboptimal for nonsevere CDI as it is less beneficial than alternative strategies. The preferred treatment regimen is fidaxomicin for nonsevere CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and FMT for subsequent recurrence. The most effective treatments, with highest cure rates, are also cost-effective due to averted mortality, utility loss, and costs of rehospitalization and/or further treatments for recurrent CDI.}, }
@article {pmid30999462, year = {2019}, author = {Jones, EW and Carlson, JM}, title = {Steady-state reduction of generalized Lotka-Volterra systems in the microbiome.}, journal = {Physical review. E}, volume = {99}, number = {3-1}, pages = {032403}, doi = {10.1103/PhysRevE.99.032403}, pmid = {30999462}, issn = {2470-0053}, mesh = {Algorithms ; Animals ; Anti-Bacterial Agents/adverse effects ; Clostridioides difficile ; Clostridium Infections/etiology/microbiology/therapy ; Computer Simulation ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Humans ; Mice ; *Models, Biological ; Population Dynamics ; }, abstract = {The generalized Lotka-Volterra (gLV) equations, a classic model from theoretical ecology, describe the population dynamics of a set of interacting species. As the number of species in these systems grow in number, their dynamics become increasingly complex and intractable. We introduce steady-state reduction (SSR), a method that reduces a gLV system of many ecological species into two-dimensional subsystems that each obey gLV dynamics and whose basis vectors are steady states of the high-dimensional model. We apply this method to an experimentally-derived model of the gut microbiome in order to observe the transition between "healthy" and "diseased" microbial states. Specifically, we use SSR to investigate how fecal microbiota transplantation, a promising clinical treatment for dysbiosis, can revert a diseased microbial state to health.}, }
@article {pmid30997086, year = {2019}, author = {Nishida, A and Imaeda, H and Inatomi, O and Bamba, S and Sugimoto, M and Andoh, A}, title = {The efficacy of fecal microbiota transplantation for patients with chronic pouchitis: A case series.}, journal = {Clinical case reports}, volume = {7}, number = {4}, pages = {782-788}, pmid = {30997086}, issn = {2050-0904}, abstract = {Pouchitis is one of the most common complications that develop after restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Single fecal microbiota transplantation (FMT) by colonoscopy was performed safely on three patients with pouchitis. However, the efficacy of FMT on pouchitis was limited.}, }
@article {pmid30995472, year = {2019}, author = {Nuriel-Ohayon, M and Neuman, H and Ziv, O and Belogolovski, A and Barsheshet, Y and Bloch, N and Uzan, A and Lahav, R and Peretz, A and Frishman, S and Hod, M and Hadar, E and Louzoun, Y and Avni, O and Koren, O}, title = {Progesterone Increases Bifidobacterium Relative Abundance during Late Pregnancy.}, journal = {Cell reports}, volume = {27}, number = {3}, pages = {730-736.e3}, doi = {10.1016/j.celrep.2019.03.075}, pmid = {30995472}, issn = {2211-1247}, support = {//CIHR/Canada ; }, mesh = {Adult ; Animals ; Bifidobacterium/genetics/*growth &amp; development/isolation &amp; purification ; Discriminant Analysis ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Mice ; Placebo Effect ; Pregnancy ; Pregnancy Trimester, Third ; Principal Component Analysis ; Progesterone/chemistry/*pharmacology ; RNA, Ribosomal, 16S/metabolism ; Young Adult ; }, abstract = {Gestation is accompanied by alterations in the microbial repertoire; however, the mechanisms driving these changes are unknown. Here, we demonstrate a dramatic shift in the gut microbial composition of women and mice during late pregnancy, including an increase in the relative abundance of Bifidobacterium. Using in-vivo-transplanted pellets, we found that progesterone, the principal gestation hormone, affects the microbial community. The effect of progesterone on the richness of several bacteria species, including Bifidobacterium, was also demonstrated in vitro, indicating a direct effect. Altogether, our results delineate a model in which progesterone promotes Bifidobacterium growth during late pregnancy.}, }
@article {pmid30994937, year = {2019}, author = {Nie, P and Li, Z and Wang, Y and Zhang, Y and Zhao, M and Luo, J and Du, S and Deng, Z and Chen, J and Wang, Y and Chen, S and Wang, L}, title = {Gut microbiome interventions in human health and diseases.}, journal = {Medicinal research reviews}, volume = {39}, number = {6}, pages = {2286-2313}, doi = {10.1002/med.21584}, pmid = {30994937}, issn = {1098-1128}, mesh = {*Disease ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Health ; Humans ; Molecular Targeted Therapy ; Signal Transduction ; }, abstract = {Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Investigation of pathogenesis has identified specific species or strains, bacterial genes, and metabolites that play roles in certain diseases and represent potential drug targets. As research progresses, gut microbiome-based diagnosis and therapy are proposed and applied, which might lead to considerable progress in precision medicine. We further discuss the limitations of current studies and potential solutions.}, }
@article {pmid30988420, year = {2019}, author = {Rashidi, A and Kaiser, T and Shields-Cutler, R and Graiziger, C and Holtan, SG and Rehman, TU and Wasko, J and Weisdorf, DJ and Dunny, G and Khoruts, A and Staley, C}, title = {Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {6083}, pmid = {30988420}, issn = {2045-2322}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; DNA, Bacterial/isolation &amp; purification ; Dysbiosis/chemically induced/diagnosis/*microbiology ; Enterococcus/genetics/*isolation &amp; purification ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Induction Chemotherapy/adverse effects/methods ; Leukemia, Myeloid, Acute/*drug therapy ; Longitudinal Studies ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Salvage Therapy/adverse effects/methods ; Sequence Analysis, DNA ; Severity of Illness Index ; Young Adult ; }, abstract = {Acute leukemia (AL) patients undergoing intensive induction chemotherapy develop severe gut dysbiosis, placing them at heightened risk for infectious complications. Some AL patients will undergo "repeat therapy" (re-induction or salvage) due to persistent or relapsed disease. We hypothesized that prior injury to the microbiome during induction may influence dysbiosis patterns during repeat therapy. To test this hypothesis, we analyzed the bacterial microbiome profiles of thrice-weekly stool samples from 20 intensively treated AL patients (first induction: 13, repeat therapy: 7) by 16S rRNA sequencing. In mixed-effects modeling, repeat therapy was a significant predictor of Enterococcus expansion (P = 0.006), independently of antibiotic exposure, disease type, feeding mode, and week of chemotherapy. Bayesian analysis of longitudinal data demonstrated larger departures of microbial communities from the pre-chemotherapy baseline during repeat therapy compared to induction. This increased ecosystem instability during repeat therapy possibly impairs colonization resistance and increases vulnerability to Enterococcus outgrowth. Microbiota restoration therapies at the end of induction or before starting subsequent therapy warrant investigation.}, }
@article {pmid30987771, year = {2019}, author = {Abreu Y Abreu, AT and Velarde-Ruiz Velasco, JA and Zavala-Solares, MR and Remes-Troche, JM and Carmona-Sánchez, RI and Aldana-Ledesma, JM and Camacho-Ortiz, A and Contreras-Omaña, R and Díaz-Seoane, R and Elizondo-Vázquez, CT and Garza-González, E and Grajales-Figueroa, G and Gómez-Escudero, O and Jacobo-Karam, JS and Morales-Arámbula, M and Olivares-Guzmán, LO and Sifuentes-Osornio, J and Siu-Moguel, AG and Soto-Solís, R and Valdovinos-García, LR and Valdovinos-Díaz, MA and Vázquez-Elizondo, G and Lazo-de la Vega Jasso, SA}, title = {Consensus on the prevention, diagnosis, and treatment of Clostridium difficile infection.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {84}, number = {2}, pages = {204-219}, doi = {10.1016/j.rgmx.2018.12.001}, pmid = {30987771}, issn = {2255-534X}, mesh = {*Clostridioides difficile ; Clostridium Infections/diagnosis/prevention &amp; control/*therapy ; Consensus ; Enterocolitis, Pseudomembranous/diagnosis ; Humans ; Mexico ; }, abstract = {In recent decades, Clostridium difficile infection (CDI) has become a worldwide health problem. Mexico is no exception, and therefore the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, endoscopists, internists, infectious disease specialists, and microbiologists) to carry out the "Consensus on the prevention, diagnosis, and treatment of Clostridium difficile infection", establishing useful recommendations (in relation to the adult population) for the medical community. Said recommendations are presented herein. Among them, it was recognized that CDI should be suspected in subjects with diarrhea that have a history of antibiotic and/or immunosuppressant use, but that it can also be a community-acquired infection. A 2-step diagnostic algorithm was proposed, in which a highly sensitive test, such as glutamate dehydrogenase (GDH), is first utilized, and if positive, confirmed by the detection of toxins through immunoassay or nucleic acid detection tests. Another recommendation was that CDI based on clinical evaluation be categorized as mild-moderate, severe, and complicated severe, given that such a classification enables better therapeutic decisions to be made. In mild-moderate CDI, oral vancomycin is the medication of choice, and metronidazole is recommended as an alternative treatment. In addition, fecal microbiota transplantation was recognized as an efficacious option in patients with recurrence or in the more severe cases of infection, and surgery should be reserved for patients with severe colitis (toxic megacolon), in whom all medical treatment has failed.}, }
@article {pmid30986885, year = {2019}, author = {Stallmach, A and Grunert, P and Pieper, D and Steube, A}, title = {[Ulcerative colitis: Does the modulation of gut microbiota induce long-lasting remission?].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {57}, number = {7}, pages = {834-842}, doi = {10.1055/a-0874-6603}, pmid = {30986885}, issn = {1439-7803}, mesh = {Colitis, Ulcerative/microbiology/pathology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Remission Induction ; Treatment Outcome ; }, abstract = {Although the pathogenesis of ulcerative colitis (UC) remains elusive, substantial progress in understanding its development and progression has been achieved in the past decades, and novel effective treatment strategies have been developed. Changes in gut microbiota, environmental triggers, deregulation of immunological responses, and genetic predisposition have been identified as pathogenic key factors. There are several lines of clinical observations, which support a close connection of altered gut microbiota with the development and course of UC. Despite a plethora of microbiota alterations in UC, it is currently unclear whether the observed changes in inflammation are cause or effect of the altered microbiota state.Fecal microbiota transplantation (FMT) provides a novel, perhaps complementary, strategy to restore gut microbial diversity, bacterial richness, and microbial homeostasis in UC. FMT is an already established treatment option for recurrent Clostridioides difficile infection, and several case series and randomized controlled trials have described its use in UC. In this review, we evaluate recent efficacy and safety data on FMT for UC, discuss possible pitfalls and show possible areas of future development. Although FMT could become a promising treatment modality for UC, based on currently available data, FMT should be only performed in clinical trials as controlled studies focusing on long-term outcomes and safety are warranted.}, }
@article {pmid30986562, year = {2019}, author = {Saha, S and Tariq, R and Tosh, PK and Pardi, DS and Khanna, S}, title = {Faecal microbiota transplantation for eradicating carriage of multidrug-resistant organisms: a systematic review.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {25}, number = {8}, pages = {958-963}, doi = {10.1016/j.cmi.2019.04.006}, pmid = {30986562}, issn = {1469-0691}, mesh = {Anti-Bacterial Agents/pharmacology ; Carrier State/microbiology/prevention &amp; control ; Clostridium Infections/*therapy ; Disease Management ; *Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Randomized Controlled Trials as Topic ; Recurrence ; }, abstract = {BACKGROUND: Multidrug-resistant (MDR) microorganism development in the gut is frequently the result of inappropriate antibiotic use. Faecal microbiota transplantation (FMT) restores normal gut microbiota in patients with Clostridium difficile infection. We hypothesized that it may help in decolonizing MDR organisms (MDROs) and in preventing recurrent MDR infections.<br><br>OBJECTIVES: To assess FMT efficacy (eradication rate) for decolonizing MDROs and preventing recurrent MDR infections.<br><br>DATA SOURCES: Medline, Embase and Web of Science (inception through 11 February 2019).<br><br>STUDY ELIGIBILITY CRITERIA: Clinical trials, retrospective studies, case reports and case series.<br><br>PARTICIPANTS: Patients with MDR infections or MDRO colonization treated with FMT.<br><br>INTERVENTIONS: FMT.<br><br>METHODS: Systematic review.<br><br>RESULTS: Twenty-one studies (one randomized clinical trial, seven uncontrolled clinical trials, two retrospective cohort studies, two case series, nine case reports) assessing 192 patients were included. Three studies assessed FMT efficacy in preventing MDR infections; 16 assessed its effect on MDRO colonization; two assessed both. Data from 151 patients were included in the final analyses. In studies with low to moderate risk of bias, the eradication rate was 37.5% to 87.5%. Efficacy was similar in studies looking at infection or colonization and did not differ by length of follow-up. No serious adverse events from FMT were reported. Seven patients died of other causes.<br><br>CONCLUSIONS: FMT could be used as a treatment for eradicating MDR colonization and possibly preventing recurrent MDR infections, once more supporting efficacy and safety data are available. Larger well-designed randomized controlled trials are needed to further explore this therapy.}, }
@article {pmid30982975, year = {2022}, author = {Costa, BCL and Dábilla, NAS and Almeida, TN and Fiaccadori, FS and de Souza, TT and Cardoso, DDDP and Arantes, AM and Souza, M}, title = {Human bocavirus detection and quantification in fecal and serum specimens from recipients of allogeneic hematopoietic stem cell transplantation: A longitudinal study.}, journal = {Journal of medical virology}, volume = {94}, number = {2}, pages = {594-600}, doi = {10.1002/jmv.25486}, pmid = {30982975}, issn = {1096-9071}, mesh = {Adolescent ; Adult ; Brazil ; Feces/*virology ; Female ; Genotype ; *Hematopoietic Stem Cell Transplantation ; Hospitalization ; Human bocavirus/*genetics/isolation &amp; purification ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Parvoviridae Infections/*virology ; Viral Load ; Viremia/*blood ; Virus Shedding ; Young Adult ; }, abstract = {OBJECTIVES: The aim of this study was to evaluate the occurrence of human bocavirus (HBoV) and to determine viral loads in samples of patients admitted for allogeneic hematopoietic stem cell transplantation (allo-HSCT).<br><br>METHODS: Fecal and serum samples were collected from 19 patients, during a 24-month period. Samples were screened by quantitative polymerase chain reaction TaqMan assay, with specific probe and primers targeting the NP1 gene of all HBoVs genotypes (HBoV-1 to -&#x2009;4), and viral loads were determined using serial dilutions of a recombinant plasmid.<br><br>RESULTS: HBoV DNA was detected in 42.1% (8 of 19) of the patients in at least one type of sample (feces and/or serum) during the study period, with 75% (6 of 8) of the patients being positive in both types of sample. Viral shedding in feces had a median of 26 days (range, 5 to 121) and viremia was detected in 87.5% (7 of 8) of the patients. The HBoV loads in fecal samples were higher than in sera and, in most cases, HBoV was detected earlier in fecal than in sera samples. In six HBoV-positive patients (6 of 8) diarrhea was observed concomitantly to viral detection in fecal samples.<br><br>CONCLUSIONS: A high frequency and loads of HBoV in allo-HSCT recipients was observed, especially in fecal samples. Positivity in fecal samples was an early predictor of HBoV presence.}, }
@article {pmid30982852, year = {2019}, author = {Steube, A and Vital, M and Grunert, P and Pieper, DH and Stallmach, A}, title = {Long-term Multidonor Faecal Microbiota Transfer by Oral Capsules for Active Ulcerative Colitis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {13}, number = {11}, pages = {1480-1481}, doi = {10.1093/ecco-jcc/jjz073}, pmid = {30982852}, issn = {1876-4479}, mesh = {Capsules ; *Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; Pilot Projects ; }, }
@article {pmid30977692, year = {2019}, author = {Belga, S and Chiang, D and Kabbani, D and Abraldes, JG and Cervera, C}, title = {The direct and indirect effects of vancomycin-resistant enterococci colonization in liver transplant candidates and recipients.}, journal = {Expert review of anti-infective therapy}, volume = {17}, number = {5}, pages = {363-373}, doi = {10.1080/14787210.2019.1607297}, pmid = {30977692}, issn = {1744-8336}, mesh = {Animals ; Anti-Bacterial Agents/*administration &amp; dosage/pharmacology ; Bacteriophages ; Fecal Microbiota Transplantation/methods ; Gram-Positive Bacterial Infections/drug therapy/*epidemiology/microbiology ; Humans ; *Liver Transplantation ; Vancomycin-Resistant Enterococci/isolation &amp; purification ; }, abstract = {Introduction: Vancomycin-resistant enterococci (VRE) colonization and subsequent infection results in increased morbidity, mortality and use of health-care resources. The burden of VRE colonization in liver transplant candidates and recipients is significant. VRE colonization is a marker of gut dysbiosis and its impact on the microbiota-liver axis, may negatively affect graft function and result in negative outcomes pre- and post-transplantation. Areas covered: In this article we describe the epidemiology of VRE colonization, risk factors for VRE infection, health-care costs associated with VRE, with a focus on the impact of VRE colonization on liver transplant recipients' fecal microbiota, the therapeutic strategies for VRE decolonization and proposed pathophysiologic mechanisms of VRE colonization in liver transplant recipients. Expert opinion: VRE colonization results in a significant loss of bacterial microbiome diversity. This may have metabolic consequences, with low production of short-chain fatty acids which may, in turn, result in immune dysregulation. As antibiotics have failed to decolonize the gut, alternative strategies such as fecal microbiota transplantation (FMT), stimulation of intestinal antimicrobial peptides and phage therapy warrants future studies.}, }
@article {pmid30976292, year = {2019}, author = {Tolonen, M and Sallinen, V and Leppäniemi, A and Bäcklund, M and Mentula, P}, title = {The role of the intra-abdominal view in complicated intra-abdominal infections.}, journal = {World journal of emergency surgery : WJES}, volume = {14}, number = {}, pages = {15}, pmid = {30976292}, issn = {1749-7922}, mesh = {Aged ; Body Mass Index ; Cohort Studies ; Digestive System Surgical Procedures/*methods ; Emergency Treatment/methods/standards ; Female ; Humans ; Intraabdominal Infections/*diagnosis/physiopathology/*surgery ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; *Prognosis ; Prospective Studies ; ROC Curve ; Retrospective Studies ; Risk Factors ; Statistics, Nonparametric ; }, abstract = {BACKGROUND: The prognostic role of what a surgeon observes in the abdomen of patients with complicated intra-abdominal infection (cIAI) is largely unknown. The aim of this prospective study was to systemically analyze components of the intra-abdominal view (IAV) and their association to severe complicated intra-abdominal sepsis (SCIAS) or mortality.<br><br>METHODS: The study cohort consisted of adult patients with cIAI. The operating surgeon filled a paper form describing the intra-abdominal view. Demographics, operative details, and preoperative physiological status were collected. Descriptive, univariate, and multivariate statistical analyses were performed, and a new score was developed based on regression coefficients. The primary outcome was a composite outcome of SCIAS or 30-day mortality, in which SCIAS was defined as organ dysfunctions requiring intensive care unit admission.<br><br>RESULTS: A total of 283 patients were analyzed. The primary outcome was encountered in 71 (25%) patients. In the IAV, independent risk factors for the primary outcome were fecal or bile as exudate (odds ratio (OR) 1.98, 95% confidence interval 1.05-3.73), diffuse peritonitis (OR 2.15, 1.02-4.55), diffuse substantial redness of the peritoneum (OR 5.73, 2.12-15.44), and a non-appendiceal source of cIAI (OR 11.20, 4.11-30.54). Based on these factors, an IAV score was developed and its performance analyzed. The area under the receiver operating characteristic for the IAV score was 0.81. The IAV score also correlated significantly with several outcomes and organ dysfunctions.<br><br>CONCLUSIONS: The extent of peritonitis, diffuse substantial redness of the peritoneum, type of exudate, and source of infection associate independently with SCIAS or mortality. A high IAV score associates with mortality and organ dysfunctions, yet it needs further external validation. Combining components of IAV into comprehensive scoring systems for cIAI patients may provide additional value compared to the current scoring systems.<br><br>TRIAL REGISTRATION: The study protocol was retrospectively registered on April 4, 2016, right after the first enrolled patient at Clinicaltrials.gov database (NCT02726932).}, }
@article {pmid30972640, year = {2019}, author = {Ding, X and Li, Q and Li, P and Zhang, T and Cui, B and Ji, G and Lu, X and Zhang, F}, title = {Long-Term Safety and Efficacy of Fecal Microbiota Transplant in Active Ulcerative Colitis.}, journal = {Drug safety}, volume = {42}, number = {7}, pages = {869-880}, pmid = {30972640}, issn = {1179-1942}, mesh = {Adolescent ; Adult ; Aged ; Child ; Colitis, Ulcerative/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Young Adult ; }, abstract = {INTRODUCTION AND OBJECTIVE: The therapeutic role of fecal microbiota transplantation in ulcerative colitis varies across different reports. This study aims to evaluate the long-term safety and efficacy of a strategy called step-up fecal microbiota transplantation for ulcerative colitis.<br><br>METHODS: Two clinical trials (NCT01790061, NCT02560727) for moderate-to-severe ulcerative colitis (Mayo score range 6-12) were performed from November 2012 to July 2017. Both studies were pooled for analysis on the safety and efficacy of fecal microbiota transplantation in patients with ulcerative colitis over a 1-year follow-up. The step-up fecal microbiota transplantation strategy included step 1: single fecal microbiota transplantation; step 2: two or more fecal microbiota transplantations; and step 3: fecal microbiota transplantations followed by immunosuppressants. Long-term clinical efficacy and adverse events were assessed, and multiple factors related to fecal microbiota transplantation were evaluated.<br><br>RESULTS: Of 134 eligible patients&#xa0;in this real-word study, 81.3% (109/134) were included for analysis. The follow-up ranged from 1 to 5&#xa0;years. Fecal microbiota transplantation-related adverse events were observed in 17.4% (43/247) of fecal microbiota transplantation procedures including one serious adverse event (myasthenia gravis) and 56 non-serious adverse events. Multivariable logistic regression analysis showed that both the method of preparation of microbiota from stool using the automatic system and the delivery method of colonic transendoscopic enteral tubing were associated with a lower rate of fecal microbiota transplantation-related adverse events (p&#x2009;=&#x2009;0.023, p&#x2009;=&#x2009;0.017, respectively). In total, 74.3% (81/109) and 51.4% (56/109) of patients achieved clinical response at 1&#xa0;month and 3&#xa0;months after step-up fecal microbiota transplantation, respectively.<br><br>CONCLUSIONS: Fecal microbiota transplantation should be a safe and promising therapy for ulcerative colitis. The improved fecal microbiota preparation and colonic transendoscopic enteral tubing might reduce the rate of adverse events in ulcerative colitis.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT01790061, NCT02560727.}, }
@article {pmid30969490, year = {2019}, author = {Galperine, TK and Guery, B}, title = {[Customised infectiology - Fecal microbiota transplantation : following the Clostridioides difficile pathway].}, journal = {Revue medicale suisse}, volume = {15}, number = {646}, pages = {776-779}, pmid = {30969490}, issn = {1660-9379}, mesh = {*Clostridioides difficile ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Humans ; Switzerland ; }, abstract = {Fecal microbiota transplantation (FMT) raised, in the recent years, a growing interest, mostly in Clostridioides difficile infections (CDI). The concept of FMT is quite simple based on the administration of fecal matter from a healthy donor to a patient with a disease related to the gut microbiota imbalance (dysbiosis). Although the theory seems straightforward, the fine mechanisms are multiple and not yet completely understood. In Switzerland, FMT is considered as a drug under the pharmacist responsibility. The only official indication for FMT is multi-recurrent CDI. For practical reasons, most of the FMT are performed with fresh stools, but development of frozen forms and capsules should considerably enhance treatment delivery. Other indications are currently investigated but not yet in the clinical routine.}, }
@article {pmid30969003, year = {2019}, author = {Alukal, J and Dutta, SK and Surapaneni, BK and Le, M and Tabbaa, O and Phillips, L and Mattar, MC}, title = {Safety and efficacy of fecal microbiota transplant in 9 critically ill patients with severe and complicated Clostridium difficile infection with impending colectomy.}, journal = {Journal of digestive diseases}, volume = {20}, number = {6}, pages = {301-307}, doi = {10.1111/1751-2980.12750}, pmid = {30969003}, issn = {1751-2980}, mesh = {Aged ; *Clostridioides difficile ; *Colectomy ; Critical Illness/therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; Preoperative Care/*methods ; Recurrence ; Treatment Outcome ; }, abstract = {OBJECTIVE: Significant data support the efficacy and safety of fecal microbiota transplant (FMT) in recurrent Clostridium difficile infection (CDI). The objective of our study was to determine the success rate of FMT in patients diagnosed with severe and complicated CDI with impending colectomy in the intensive care setting.<br><br>METHODS: This was a 2-center study of 9 patients who met the criteria for severe and complicated CDI and had an impending colectomy. All 9 patients had failed conventional antibiotic therapy and were deemed too unstable to undergo a colectomy. Hence, FMT was considered to be the next step in managing their condition.<br><br>RESULTS: Following FMT there was marked improvement in the patients' clinical status, with the resolution of diarrhea, reduced requirement for vasopressor, and the reduction in abdominal distention and pain. The primary cure rate of our study after a single round of FMT was 78% (7/9). Of the 9 patients 8 (88.88%) avoided a colectomy during the same hospital admission. the CDI-related death rate was 12.5% (1/9) and that of non-CDI was 12.5% (1/9).<br><br>CONCLUSION: Our success with FMT in fulminant CDI shows that this therapeutic modality is a promising alternative to a colectomy and could be a potential bowel-saving intervention.}, }
@article {pmid30967971, year = {2019}, author = {Mrazek, K and Bereswill, S and Heimesaat, MM}, title = {Fecal Microbiota Transplantation Decreases Intestinal Loads of Multi-Drug Resistant Pseudomonas aeruginosa in Murine Carriers.}, journal = {European journal of microbiology &amp; immunology}, volume = {9}, number = {1}, pages = {14-22}, pmid = {30967971}, issn = {2062-509X}, abstract = {Intestinal carriage of multi-drug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa (Psae) constitutes a pivotal prerequisite for subsequent fatal endogenous infections in patients at risk. We here addressed whether fecal microbiota transplantation (FMT) could effectively combat MDR-Psae carriage. Therefore, secondary abiotic mice were challenged with MDR-Psae by gavage. One week later, mice were subjected to peroral FMT from either murine or human donors on 3 consecutive days. Irrespective of murine or human origin of fecal transplant, intestinal MDR-Psae loads decreased as early as 24 h after the initial FMT. Remarkably, the murine FMT could lower intestinal MDR-Psae burdens by approximately 4 log orders of magnitude within 1 week. In another intervention study, mice harboring a human gut microbiota were perorally challenged with MDR-Psae and subjected to murine FMT on 3 consecutive days, 1 week later. Strikingly, within 5 days, murine FMT resulted in lower loads and carrier rates of MDR-Psae in mice with a human gut microbiota. In conclusion, FMT might be a promising antibiotics-independent option to combat intestinal MDR-Psae carriage and thus prevent from future endogenous infections of patients at risk.}, }
@article {pmid30967875, year = {2019}, author = {Bereswill, S and Escher, U and Grunau, A and Kühl, AA and Dunay, IR and Tamas, A and Reglodi, D and Heimesaat, MM}, title = {Pituitary Adenylate Cyclase-Activating Polypeptide-A Neuropeptide as Novel Treatment Option for Subacute Ileitis in Mice Harboring a Human Gut Microbiota.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {554}, pmid = {30967875}, issn = {1664-3224}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Humans ; *Ileitis/immunology/pathology/therapy ; *Inflammatory Bowel Diseases/immunology/pathology/therapy ; Interleukin-6/immunology ; Mice ; Pituitary Adenylate Cyclase-Activating Polypeptide/*immunology ; T-Lymphocytes/immunology/pathology ; Toxoplasma/immunology ; Toxoplasmosis/immunology ; Tumor Necrosis Factor-alpha/immunology ; }, abstract = {The neuropeptide Pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its important functions in immunity and inflammation. Data regarding anti-inflammatory properties of PACAP in the intestinal tract are limited, however. In our present preclinical intervention study we addressed whether PACAP treatment could alleviate experimental subacute ileitis mimicking human gut microbiota conditions. Therefore, secondary abioitic mice were subjected to human fecal microbiota transplantation (FMT) and perorally infected with low-dose Toxoplasma gondii to induce subacute ileitis on day 0. From day 3 until day 8 post-infection, mice were either treated with synthetic PACAP38 or placebo. At day 9 post-infection, placebo, but not PACAP treated mice exhibited overt macroscopic sequelae of intestinal immunopathology. PACAP treatment further resulted in less distinct apoptotic responses in ileal and colonic epithelia that were accompanied by lower T cell numbers in the mucosa and lamina propria and less secretion of pro-inflammatory cytokines in intestinal ex vivo biopsies. Notably, ileitis-associated gut microbiota shifts were less distinct in PACAP as compared to placebo treated mice. Inflammation-ameliorating effects of PACAP were not restricted to the intestines, but could also be observed in extra-intestinal including systemic compartments as indicated by lower apoptotic cell counts and less pro-inflammatory cytokine secretion in liver and lungs taken from PACAP treated as compared to placebo control mice, which also held true for markedly lower serum TNF and IL-6 concentrations in the former as compared to the latter. Our preclinical intervention study provides strong evidence that synthetic PACAP alleviates subacute ileitis and extra-intestinal including systemic sequelae of T cell-driven immunopathology. These findings further support PACAP as a novel treatment option for intestinal inflammation including inflammatory bowel diseases (IBD).}, }
@article {pmid30967657, year = {2019}, author = {Kang, DW and Adams, JB and Coleman, DM and Pollard, EL and Maldonado, J and McDonough-Means, S and Caporaso, JG and Krajmalnik-Brown, R}, title = {Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {5821}, pmid = {30967657}, issn = {2045-2322}, mesh = {Autistic Disorder/*physiopathology/*therapy ; Bifidobacterium/isolation &amp; purification ; Child ; Dysbiosis/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Gastrointestinal Diseases/therapy ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/microbiology ; Humans ; Male ; Prevotella/isolation &amp; purification ; }, abstract = {Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.}, }
@article {pmid30967260, year = {2019}, author = {He, Y and Yu, H and Ge, Y and Li, X and Jiang, M and Liu, Y and Li, X and Wang, Y and Guo, M and Qin, X and Wang, X}, title = {Bacterial β-glucuronidase alleviates dextran sulfate sodium-induced colitis in mice: A possible crucial new diagnostic and therapeutic target for inflammatory bowel disease.}, journal = {Biochemical and biophysical research communications}, volume = {513}, number = {2}, pages = {426-433}, doi = {10.1016/j.bbrc.2019.03.196}, pmid = {30967260}, issn = {1090-2104}, mesh = {Animals ; Colitis/chemically induced/*drug therapy/pathology ; Dextran Sulfate ; Disease Models, Animal ; Escherichia coli/*enzymology ; Glucuronidase/*therapeutic use ; Inflammatory Bowel Diseases/chemically induced/*drug therapy/pathology ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVE: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are devastating diseases of the gut. At present, all the treatments are mainly targeting symptoms like inflammation. The disease remains regarded as incurable, largely due to lacking of knowledge on its etiology. Our previous studies suggested that impaired inactivation of digestive proteases by deconjugated bilirubin in experimental colitis, thus bacterial β-glucuronidase for catalyzing the reaction, may have played critical role in the pathogenesis of IBD.<br><br>METHODS: We first analyzed &#x3b2;-glucuronidase activity in gut tissue and feces of mice by a colitis model. Then the effect of &#x3b2;-glucuronidase on experimental colitis was investigated in detail by administration of &#x3b2;-glucuronidase (from E.&#xa0;coli) and fecal material transplantation to mice with 3% DSS in drinking water for 7 days.<br><br>RESULTS: Mice with colitis showed unchanged activity of &#x3b2;-glucuronidase in colon tissue but decreased activity in feces. Treatment with bacterial &#x3b2;-glucuronidase at 100 U or above alleviated DSS-induced colitis as demonstrated by the less body weight loss, less disease activity score, increased expression of tight junction proteins and decreased gut permeability, decreases in MPO, TNF-&#x3b1;, IL-1&#x3b2;, TLR-4 and MyD88, and increase in IL-10 and I&#x3ba;B&#x3b1; in gut, restored fecal &#x3b2;-glucuronidase and gut microbiota along with decreases in fecal digestive proteases. Transplantation of fecal material from control to colitis mice showed similar effects as treatment with &#x3b2;-glucuronidase.<br><br>CONCLUSIONS: Bacterial &#x3b2;-glucuronidase showed strong inhibition on colitis along with the reduction in fecal digestive proteases, which may be a crucial diagnostic and therapeutic target for IBD.}, }
@article {pmid30965098, year = {2019}, author = {Kuijper, EJ and Vendrik, KEW and Vehreschild, MJGT}, title = {Manipulation of the microbiota to eradicate multidrug-resistant Enterobacteriaceae from the human intestinal tract.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {25}, number = {7}, pages = {786-789}, doi = {10.1016/j.cmi.2019.03.025}, pmid = {30965098}, issn = {1469-0691}, mesh = {Anti-Bacterial Agents ; Enterobacteriaceae ; Enterobacteriaceae Infections/*microbiology ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid30957511, year = {2019}, author = {Green, J and Castle, D and Berk, M and Hair, C and Loughman, A and Cryan, J and Nierenberg, A and Athan, E and Jacka, F}, title = {Faecal microbiota transplants for depression - Who gives a crapsule?.}, journal = {The Australian and New Zealand journal of psychiatry}, volume = {53}, number = {8}, pages = {732-734}, doi = {10.1177/0004867419839776}, pmid = {30957511}, issn = {1440-1614}, mesh = {Animals ; Depression/*therapy ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid30957161, year = {2019}, author = {Tariq, R and Pardi, DS and Bartlett, MG and Khanna, S}, title = {Low Cure Rates in Controlled Trials of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {68}, number = {8}, pages = {1351-1358}, doi = {10.1093/cid/ciy721}, pmid = {30957161}, issn = {1537-6591}, mesh = {Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Randomized Controlled Trials as Topic ; Recurrence ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridium difficile infection (CDI) in observational studies (>90%), but cure rates in clinical trials are lower. We performed a systematic review and meta-analysis to assess the efficacy of FMT for recurrent CDI in open-label studies and clinical trials .<br><br>METHODS: A systematic search from January 1978 to March 2017 was performed to include clinical trials of FMT for CDI. We analyzed CDI resolution by calculating weighted pooled rates (WPRs).<br><br>RESULTS: Thirteen trials were included, comprising 610 patients with CDI treated with single FMT. Overall, 439 patients had clinical cure (WPR, 76.1%; 95% confidence interval (CI), 66.4%-85.7%). There was significant heterogeneity among studies (I2 = 91.35%). Cure rates were lower in randomized trials (139/216 patients; WPR, 67.7%; 95% CI, 54.2%-81.3%) than in open-label studies (300/394 patients; WPR, 82.7%; 71.1%-94.3%) (P < .001). Subgroup analysis by FMT delivery modality showed lower cure rates with enema than colonoscopy (WPR, 66.3% vs 87.4%; P < .001) but no difference between colonoscopy and oral delivery (WPR, 87.4% vs 81.4%; P = .17). Lower rates were seen for studies including both recurrent and refractory CDI than for those including only recurrent CDI (WPR, 63.9% vs 79%; P < .001).<br><br>CONCLUSIONS: FMT was associated with lower cure rates in randomized trials than in open-label and in observational studies. Colonoscopy and oral route are more effective than enema for stool delivery. The efficacy also seems to be higher for recurrent than for refractory CDI.}, }
@article {pmid30953261, year = {2019}, author = {Hu, L and Wang, Q and Zhang, X and Xu, L and Wang, Y and Yan, C and Chen, H and Chen, Y and Liu, K and Wang, H and Huang, X and Mo, X}, title = {Positive stool culture could predict the clinical outcomes of haploidentical hematopoietic stem cell transplantation.}, journal = {Frontiers of medicine}, volume = {13}, number = {4}, pages = {492-503}, pmid = {30953261}, issn = {2095-0225}, mesh = {Adolescent ; Adult ; Aged ; Candida/*isolation &amp; purification ; Child ; Child, Preschool ; Disease-Free Survival ; Feces/*microbiology ; Female ; Graft vs Host Disease/etiology/*mortality ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Retrospective Studies ; Young Adult ; }, abstract = {We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) (n = 332). PSCs were observed in 61 patients (PSC group, 18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and Candida in stool specimens was related to a higher risk of platelet engraftment failure. The cumulative incidence of infection-related mortality 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group; 19.2% vs. 8.9%, P = 0.017). The probabilities of overall survival (71.4% vs. 83.8%, P = 0.031) and disease-free survival (69.6% vs. 81.0%, P = 0.048) 1 year after haplo-HSCT for the PSC group were significantly lower than those for the NSC group, particularly for patients who had Candida in their stool specimens. In multivariate analysis, Candida in stool specimens significantly increased the risk of mortality and was associated with poorer survival. Our results showed that PSC influenced the clinical outcomes after haplo-HSCT, particularly those who had Candida in their stool specimens.}, }
@article {pmid30947289, year = {2019}, author = {Li, SX and Sen, S and Schneider, JM and Xiong, KN and Nusbacher, NM and Moreno-Huizar, N and Shaffer, M and Armstrong, AJS and Severs, E and Kuhn, K and Neff, CP and McCarter, M and Campbell, T and Lozupone, CA and Palmer, BE}, title = {Gut microbiota from high-risk men who have sex with men drive immune activation in gnotobiotic mice and in vitro HIV infection.}, journal = {PLoS pathogens}, volume = {15}, number = {4}, pages = {e1007611}, pmid = {30947289}, issn = {1553-7374}, support = {T32 AI007447/AI/NIAID NIH HHS/United States ; R01 DK104047/DK/NIDDK NIH HHS/United States ; K08 DK107905/DK/NIDDK NIH HHS/United States ; R01 HL138639/HL/NHLBI NIH HHS/United States ; T32 AI052066/AI/NIAID NIH HHS/United States ; R01 DK108366/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Animals ; Cohort Studies ; DNA, Bacterial/genetics ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; Germ-Free Life/*immunology ; HIV/genetics/*immunology ; HIV Infections/*immunology/microbiology/virology ; *Homosexuality, Male ; Humans ; In Vitro Techniques ; Male ; Mice ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Sexual Behavior ; Young Adult ; }, abstract = {Men who have sex with men (MSM) have differences in immune activation and gut microbiome composition compared with men who have sex with women (MSW), even in the absence of HIV infection. Gut microbiome differences associated with HIV itself when controlling for MSM, as assessed by 16S rRNA sequencing, are relatively subtle. Understanding whether gut microbiome composition impacts immune activation in HIV-negative and HIV-positive MSM has important implications since immune activation has been associated with HIV acquisition risk and disease progression. To investigate the effects of MSM and HIV-associated gut microbiota on immune activation, we transplanted feces from HIV-negative MSW, HIV-negative MSM, and HIV-positive untreated MSM to gnotobiotic mice. Following transplant, 16S rRNA gene sequencing determined that the microbiomes of MSM and MSW maintained distinct compositions in mice and that specific microbial differences between MSM and MSW were replicated. Immunologically, HIV-negative MSM donors had higher frequencies of blood CD38+ HLADR+ and CD103+ T cells and their fecal recipients had higher frequencies of gut CD69+ and CD103+ T cells, compared with HIV-negative MSW donors and recipients, respectively. Significant microbiome differences were not detected between HIV-negative and HIV-positive MSM in this small donor cohort, and immune differences between their recipients were trending but not statistically significant. A larger donor cohort may therefore be needed to detect immune-modulating microbes associated with HIV. To investigate whether our findings in mice could have implications for HIV replication, we infected primary human lamina propria cells stimulated with isolated fecal microbiota, and found that microbiota from MSM stimulated higher frequencies of HIV-infected cells than microbiota from MSW. Finally, we identified several microbes that correlated with immune readouts in both fecal recipients and donors, and with in vitro HIV infection, which suggests a role for gut microbiota in immune activation and potentially HIV acquisition in MSM.}, }
@article {pmid30946615, year = {2019}, author = {Cold, F and Browne, PD and Günther, S and Halkjaer, SI and Petersen, AM and Al-Gibouri, Z and Hansen, LH and Christensen, AH}, title = {Multidonor FMT capsules improve symptoms and decrease fecal calprotectin in ulcerative colitis patients while treated - an open-label pilot study.}, journal = {Scandinavian journal of gastroenterology}, volume = {54}, number = {3}, pages = {289-296}, doi = {10.1080/00365521.2019.1585939}, pmid = {30946615}, issn = {1502-7708}, mesh = {Adolescent ; Adult ; Capsules ; Colitis, Ulcerative/*therapy ; *Fecal Microbiota Transplantation ; Feces/chemistry ; Female ; Humans ; Leukocyte L1 Antigen Complex/*analysis ; Male ; *Microbiota ; Middle Aged ; Pilot Projects ; Prospective Studies ; Quality of Life ; Remission Induction ; Young Adult ; }, abstract = {Background: Growing evidence indicates that gut dysbiosis is a factor in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) appears to be promising in inducing UC remission, but there are no reports regarding administration using capsules. Methods: Seven patients with active UC, aged 27-50 years, were treated with 25 multidonor FMT capsules daily for 50 days as a supplement to their standard treatment in an open-label pilot study. The primary objective was to follow symptoms through the Simple Clinical Colitis Activity Index (SCCAI). Secondary objectives were to follow changes in fecal calprotectin and microbial diversity through fecal samples and quality of life through the Inflammatory Bowel Disease Questionnaire (IBDQ). Participants were followed through regular visits for six months. Results: From a median of 6 at baseline, the SCCAI of all participants decreased, with median decreases of 5 (p = .001) and 6 (p = .001) after 4 and 8 weeks, respectively. Three of the seven patients had flare-up/relapse of symptoms after the active treatment period. The median F-calprotectin of ≥1800 mg/kg at baseline decreased significantly during the treatment period, but increased again in the follow-up period. The median IBDQ improved at all visits compared to baseline. The fecal microbiota α-diversity did not increase in the study period compared to baseline. All participants completed the treatment and no serious adverse events were reported. Conclusion: Fifty days of daily multidonor FMT capsules temporarily improved symptoms and health-related life quality and decreased F-calprotectin in patients with active UC.}, }
@article {pmid30946283, year = {2021}, author = {Boccasanta, P and Venturi, M and Agradi, S and Vergani, C and Calabrò, G and Missaglia, C and Bordoni, L and Longo, A}, title = {A Minimally Invasive Technique for the 1-Stage Treatment of Complex Pelvic Floor Diseases: Laparoscopic-Pelvic Organ Prolapse Suspension.}, journal = {Female pelvic medicine &amp; reconstructive surgery}, volume = {27}, number = {1}, pages = {28-33}, doi = {10.1097/SPV.0000000000000722}, pmid = {30946283}, issn = {2154-4212}, mesh = {Adult ; Aged ; Constipation/etiology/surgery ; Female ; Genital Diseases, Female/etiology/surgery ; Gynecologic Surgical Procedures/adverse effects/methods ; Humans ; *Laparoscopy/adverse effects ; Middle Aged ; Pelvic Floor Disorders/*surgery ; Pelvic Organ Prolapse/complications/*surgery ; Prospective Studies ; Treatment Outcome ; Urologic Diseases/etiology/surgery ; }, abstract = {OBJECTIVE: The aim of this prospective study was to assess the safety and effectiveness of a new single laparoscopic operation devised to relieve obstructed defecation, gynecologic and urinary symptoms in a large series of female patients with multiorgan pelvic prolapse.<br><br>METHODS: We submitted 384 female patients to laparoscopic pelvic organ prolapse suspension operation, a new technique based on suspension of the middle pelvic compartment, by using a polypropylene mesh and followed up 368 of them, with defecography performed 12 months after surgery and a standardized protocol.<br><br>RESULTS: The 368 patients were followed-up for 36.3 (&#xb1;4.4) months, Recurrence rate was 4.9% for obstructed defecation syndrome and 3.3% for stress urinary incontinence. Complication rate was 2.9%. The mean period of daily activity resumption was 16.3 days (&#xb1;4.8 days). Anorectal and urogynecologic symptoms and scores significantly improved after the operation (P < 0.001), with no worsening of anal continence. Incidence of postoperative fecal urgency was 0%. Postoperative defecography showed a significant (P < 0.001) improvement of all parameters in 315 patients (82%). Short Form 36 Health Survey score significantly improved after the operation (P < 0.01). An excellent/good overall Satisfaction Index was reported by 78.0% of patients.<br><br>CONCLUSIONS: In our experience the Laparoscopic-Pelvic Organ Prolapse Suspension seems to be safe and effective as a 1-stage treatment of associated pelvic floor diseases. Randomized studies with an appropriate control group and longer follow-up are now needed to assess the effectiveness of this promising technique.}, }
@article {pmid30945014, year = {2019}, author = {Czepiel, J and Dróżdż, M and Pituch, H and Kuijper, EJ and Perucki, W and Mielimonka, A and Goldman, S and Wultańska, D and Garlicki, A and Biesiada, G}, title = {Clostridium difficile infection: review.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {38}, number = {7}, pages = {1211-1221}, pmid = {30945014}, issn = {1435-4373}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*drug effects/pathogenicity ; Clostridium Infections/diagnosis/*prevention &amp; control/*therapy/transmission ; Colitis/microbiology ; Cross Infection/microbiology/*therapy ; Diarrhea/*microbiology ; Disease Reservoirs/microbiology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Risk Factors ; Virulence ; }, abstract = {Clostridium difficile (C. difficile) is a Gram-positive, spore-forming, anaerobic bacillus, which is widely distributed in the intestinal tract of humans and animals and in the environment. In the last decade, the frequency and severity of C. difficile infection has been increasing worldwide to become one of the most common hospital-acquired infections. Transmission of this pathogen occurs by the fecal-oral route and the most important risk factors include antibiotic therapy, old age, and hospital or nursing home stay. The clinical picture is diverse and ranges from asymptomatic carrier status, through various degrees of diarrhea, to the most severe, life threatening colitis resulting with death. Diagnosis is based on direct detection of C. difficile toxins in feces, most commonly with the use of EIA assay, but no single test is suitable as a stand-alone test confirming CDI. Antibiotics of choice are vancomycin, fidaxomicin, and metronidazole, though metronidazole is considered as inferior. The goal of this review is to update physicians on current scientific knowledge of C. difficile infection, focusing also on fecal microbiota transplantation which is a promising therapy.}, }
@article {pmid30944372, year = {2019}, author = {Larsen, OFA and Koning, AHJ and van der Spek, PJ and Claassen, E}, title = {Towards a rational design of faecal transplant analogues.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {5558}, pmid = {30944372}, issn = {2045-2322}, mesh = {Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Microbial Consortia ; Models, Biological ; }, abstract = {Faecal transplants (microbiota transfer) have shown to be promising therapies having a wide range of therapeutic applications. However, current safety considerations hamper further valorisation. As such, well designed faecal transplant analogues provide an interesting alternative to minimize possible safety aspects. However, to date little knowledge on how to rationally design such analogues exists. Here, we show by applying first order basic graph theory that such analogues dedicated to restoring a specific physiological functionality (a microbial guild) should consist of 5-6 species to maximize stability, efficiency, and minimize safety issues and production costs.}, }
@article {pmid30943129, year = {2019}, author = {Selvanderan, SP and Goldblatt, F and Nguyen, NQ and Costello, SP}, title = {Faecal microbiota transplantation for Clostridium difficile infection resulting in a decrease in psoriatic arthritis disease activity.}, journal = {Clinical and experimental rheumatology}, volume = {37}, number = {3}, pages = {514-515}, pmid = {30943129}, issn = {0392-856X}, mesh = {Arthritis, Psoriatic/microbiology/therapy ; *Clostridium Infections/microbiology/therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid30940601, year = {2019}, author = {Wardill, HR and Secombe, KR and Bryant, RV and Hazenberg, MD and Costello, SP}, title = {Adjunctive fecal microbiota transplantation in supportive oncology: Emerging indications and considerations in immunocompromised patients.}, journal = {EBioMedicine}, volume = {44}, number = {}, pages = {730-740}, pmid = {30940601}, issn = {2352-3964}, mesh = {Animals ; Clostridium Infections/etiology/therapy ; Colitis/*etiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Gastrointestinal Microbiome ; Humans ; *Immunocompromised Host ; Neoplasms/*complications ; *Palliative Care/methods ; }, abstract = {FMT has gained enormous momentum in the treatment of acute inflammatory and infectious diseases. Despite an encouraging safety profile, FMT has been met with caution in the oncological setting due to perceived infectious risks in immunocompromised patients. Theoretical risks aside, the application of FMT in oncology may stand to benefit patients, via modulation of treatment efficacy and the mitigation of treatment complications. Here, we summarize most recent safety data of FMT in immunocompromised cohorts, including people with cancer, highlighting that FMT may actually provide protection against bacterial translocation via introduction of a diverse microbiome and restoration of epithelial defenses. We also discuss the emerging translational applications of FMT within supportive oncology, including the prevention and treatment of graft vs. host disease and sepsis, treatment of immunotherapy-induced colitis and restoration of the gut microbiome in survivors of childhood cancer.}, }
@article {pmid30938773, year = {2019}, author = {Jayasudha, R and Kalyana Chakravarthy, S and Sai Prashanthi, G and Sharma, S and Tyagi, M and Shivaji, S}, title = {Implicating Dysbiosis of the Gut Fungal Microbiome in Uveitis, an Inflammatory Disease of the Eye.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {60}, number = {5}, pages = {1384-1393}, doi = {10.1167/iovs.18-26426}, pmid = {30938773}, issn = {1552-5783}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteria/genetics ; Case-Control Studies ; Dysbiosis/*physiopathology ; Feces/microbiology ; Female ; Fungi ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Uveitis/*microbiology ; Young Adult ; }, abstract = {PURPOSE: In this study, the gut fungal microbiome of uveitis (UVT) patients was generated and compared with healthy controls (HC) to identify dysbiosis in UVT patients and ascertain the role of gut fungal microbiome in disease pathology.<br><br>METHODS: In the present study, gut fungal microbiomes were analyzed in the fecal samples of HC (n = 24) and UVT patients (n = 14) using high-throughput Illumina sequencing of ITS2 region of the fungal ribosomal RNA. QIIME and R software were used for data analysis.<br><br>RESULTS: The gut fungal richness and diversity were significantly decreased in UVT patients compared to HC. Our analyses showed enrichment of several pathogenic fungi including Malassezia restricta, Candida albicans, Candida glabrata, and Aspergillus gracilis in UVT patients. Heatmap and discriminatory OTUs further confirmed the disparities between UVT and HC microbiomes.<br><br>CONCLUSIONS: This is the first study demonstrating dysbiosis in the gut fungal communities of UVT patients indicating the importance of fungal microbiome in the disease pathology. These initial findings might warrant further investigation into the fungal microbiome, especially interactions between fungal and bacterial that then might give further insight into how probiotics or fecal transplants might benefit.}, }
@article {pmid30936486, year = {2019}, author = {Ingle, H and Lee, S and Ai, T and Orvedahl, A and Rodgers, R and Zhao, G and Sullender, M and Peterson, ST and Locke, M and Liu, TC and Yokoyama, CC and Sharp, B and Schultz-Cherry, S and Miner, JJ and Baldridge, MT}, title = {Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ.}, journal = {Nature microbiology}, volume = {4}, number = {7}, pages = {1120-1128}, pmid = {30936486}, issn = {2058-5276}, support = {R01 AI141478/AI/NIAID NIH HHS/United States ; R01 AI139314/AI/NIAID NIH HHS/United States ; T32 AI007163/AI/NIAID NIH HHS/United States ; R21 AI135254/AI/NIAID NIH HHS/United States ; R01 AI143982/AI/NIAID NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; K08 AR070918/AR/NIAMS NIH HHS/United States ; R01 AI127552/AI/NIAID NIH HHS/United States ; K22 AI127846/AI/NIAID NIH HHS/United States ; R03 AI126101/AI/NIAID NIH HHS/United States ; T32 AI106688/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Astroviridae/classification/genetics/isolation &amp; purification/physiology ; Caliciviridae Infections/immunology/*prevention &amp; control/virology ; Fecal Microbiota Transplantation ; Feces/virology ; Female ; Gastroenteritis/immunology/*prevention &amp; control/virology ; Gastrointestinal Tract/metabolism/*virology ; *Immunocompromised Host ; Interferons/*metabolism ; Intestinal Mucosa/metabolism ; Male ; Mice ; Norovirus/*immunology ; Signal Transduction ; Virus Shedding ; }, abstract = {Commensal microbes profoundly impact host immunity to enteric viral infections[1]. We have shown that the bacterial microbiota and host antiviral cytokine interferon-λ (IFN-λ) determine the persistence of murine norovirus in the gut[2,3]. However, the effects of the virome in modulating enteric infections remain unexplored. Here, we report that murine astrovirus can complement primary immunodeficiency to protect against murine norovirus and rotavirus infections. Protection against infection was horizontally transferable between immunocompromised mouse strains by co-housing and fecal transplantation. Furthermore, protection against enteric pathogens corresponded with the presence of a specific strain of murine astrovirus in the gut, and this complementation of immunodeficiency required IFN-λ signalling in gut epithelial cells. Our study demonstrates that elements of the virome can protect against enteric pathogens in an immunodeficient host.}, }
@article {pmid30930793, year = {2019}, author = {Toral, M and Robles-Vera, I and de la Visitación, N and Romero, M and Yang, T and Sánchez, M and Gómez-Guzmán, M and Jiménez, R and Raizada, MK and Duarte, J}, title = {Critical Role of the Interaction Gut Microbiota - Sympathetic Nervous System in the Regulation of Blood Pressure.}, journal = {Frontiers in physiology}, volume = {10}, number = {}, pages = {231}, pmid = {30930793}, issn = {1664-042X}, abstract = {Association between gut dysbiosis and neurogenic diseases, such as hypertension, has been described. The aim of this study was to investigate whether changes in the gut microbiota alter gut-brain interactions inducing changes in blood pressure (BP). Recipient normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were orally gavaged with donor fecal contents from SHR and WKY. We divided the animals into four groups: WKY transplanted with WKY microbiota (W-W), SHR with SHR (S-S), WKY with SHR (W-S) and SHR with WKY (S-W). Basal systolic BP (SBP) and diastolic BP (DBP) were reduced with no change in heart rate as a result of fecal microbiota transplantation (FMT) from WKY rats to SHR. Similarly, FMT from SHR to WKY increased basal SBP and DBP. Increases in both NADPH oxidase-driven reactive oxygen species production and proinflammatory cytokines in brain paraventricular nucleus linked to higher BP drop with pentolinium and plasmatic noradrenaline (NA) levels were found in the S-S group as compared to the W-W group. These parameters were reduced by FMT from WKY to SHR. Increased levels of pro-inflammatory cytokines, tyrosine hydroxylase mRNA levels and NA content in the proximal colon, whereas reduced mRNA levels of gap junction proteins, were found in the S-S group as compared to the W-W group. These changes were inhibited by FMT from WKY to SHR. According to our correlation analyses, the abundance of Blautia and Odoribacter showed a negative correlation with high SBP. In conclusion, in SHR gut microbiota is an important factor involved in BP control, at least in part, as consequence of its effect on neuroinflammation and the sympathetic nervous system activity.}, }
@article {pmid30929665, year = {2019}, author = {Caesar, R}, title = {Pharmacologic and Nonpharmacologic Therapies for the Gut Microbiota in Type 2 Diabetes.}, journal = {Canadian journal of diabetes}, volume = {43}, number = {3}, pages = {224-231}, doi = {10.1016/j.jcjd.2019.01.007}, pmid = {30929665}, issn = {2352-3840}, mesh = {Diabetes Mellitus, Type 2/immunology/metabolism/*microbiology ; Diet Therapy ; Dietary Fiber/therapeutic use ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Glucose/*metabolism ; Humans ; Immunity, Innate ; Metformin/adverse effects/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {The gut microbiota is an important regulator of host metabolism. Metagenome analyses have demonstrated that the gut microbiota differs between patients with type 2 diabetes and healthy subjects, and several studies have shown that impaired glucose metabolism is associated with decreased levels of butyrate-producing bacteria. Gut microbiota-produced metabolites, such as short-chain fatty acids, amino acid derivatives and secondary bile acids, participate in metabolic and immunologic processes and, hence, pose putative links between the gut microbiota and glucose homeostasis. Strategies to prevent and treat type 2 diabetes through manipulation of the gut microbiota are being developed. These include replacement of the gut microbiota by fecal transplantation, consumption of fibres to promote the function and growth of beneficial bacteria and treatment with probiotic bacterial strains. Furthermore, it has been shown that many drugs, including drugs used for treatment of diabetes, have major impacts on gut microbiota and, thereby, potentially on glucose metabolism. In particular, the commonly used drug metformin has been shown to influence the functional capacity of the gut microbiota, and recent evidence indicates that this may contribute to the antidiabetes effect of metformin.}, }
@article {pmid30928978, year = {2020}, author = {Gorbovskaya, I and Kanji, S and Liu, JCW and MacKenzie, NE and Agarwal, SM and Marshe, VS and Sriretnakumar, V and Verdu, EF and Bercik, P and De Palma, G and Hahn, MK and Müller, DJ}, title = {Investigation of the Gut Microbiome in Patients with Schizophrenia and Clozapine-Induced Weight Gain: Protocol and Clinical Characteristics of First Patient Cohorts.}, journal = {Neuropsychobiology}, volume = {79}, number = {1}, pages = {5-12}, doi = {10.1159/000494696}, pmid = {30928978}, issn = {1423-0224}, mesh = {Adult ; Animals ; Antipsychotic Agents/*adverse effects ; Clozapine/*adverse effects ; Disease Models, Animal ; Drug-Related Side Effects and Adverse Reactions/*therapy ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Prospective Studies ; Schizophrenia/*drug therapy/*microbiology ; Weight Gain/*drug effects ; }, abstract = {BACKGROUND: Emerging evidence suggests an important role of the human gut microbiome in psychiatry and neurodevelopmental disorders. An increasing body of literature based on animal studies has reported that the gut microbiome influences brain development and behavior by interacting with the gut-brain axis. Furthermore, as the gut microbiome has an important role in metabolism and is known to interact with pharmaceuticals, recent evidence suggests a role for the microbiome in antipsychotic-induced metabolic side effects in animals and humans.<br><br>PURPOSE: Here we present the protocol for a two-phase study investigating the gut microbiome in healthy controls and in patients with schizophrenia treated with antipsychotics.<br><br>METHODS: Phase I of our study involves humans exclusively. We recruit 25 patients who are chronically treated with clozapine and compare them with 25 healthy controls matched for age, sex, BMI, and smoking status. A second cohort consists of 25 patients newly starting on clozapine, and a third cohort includes 25 antipsychotic-naive patients. The patients in the second cohort and third cohort are prospectively assessed for up to 6 and 12 weeks, respectively. Phase II of this study will incorporate microbiota humanized mouse models to examine the influence of human fecal transplant on metabolic parameters and the gut-brain axis. Progress and Future Directions: We are underway with the first participants enrolled in all phase I treatment cohorts. This study will contribute to elucidating the role of the gut microbiome in schizophrenia and metabolic side effects. In addition, its results may help to explore potential therapeutic targets for antipsychotic-induced metabolic side effects.}, }
@article {pmid30926290, year = {2019}, author = {Tavoukjian, V}, title = {Faecal microbiota transplantation for the decolonization of antibiotic-resistant bacteria in the gut: a systematic review and meta-analysis.}, journal = {The Journal of hospital infection}, volume = {102}, number = {2}, pages = {174-188}, doi = {10.1016/j.jhin.2019.03.010}, pmid = {30926290}, issn = {1532-2939}, mesh = {Bacterial Infections/microbiology/*therapy ; Carrier State/microbiology/*therapy ; *Drug Resistance, Bacterial ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; ROC Curve ; Treatment Outcome ; }, abstract = {Antibiotic resistance is a growing global problem associated with increased morbidity and mortality, and presents a significant financial and economic burden on healthcare. Faecal microbiota transplantation (FMT) has been proven effective for curing recurrent Clostridium difficile infections, however no systematic review to date has addressed its effectiveness for decolonization of antibiotic-resistant bacteria from the gut. The aim of this study was to establish whether faecal microbiota transplantation decolonizes antibiotic-resistant bacteria from the gut of colonized adults. A systematic review was performed by undertaking a comprehensive search on MEDLINE, Embase, CENTRAL, PubMed and CINAHL databases for evidence up until May 2018. Randomized and non-randomized studies evaluating the effects of FMT on gut colonization of antibiotic-resistant bacteria in adults were eligible. Studies were assessed using the Joanna Briggs Institution critical appraisal checklists. Quality of reporting was assessed using PROCESS and CARE checklists. Data was synthesized narratively, along with a meta-analysis of proportions for the primary outcome. Five studies with a total number of 52 participants were included. Evidence of low quality showed that decolonization was achieved in half of the cases one month after FMT with higher response noted in Pseudomonas aeruginosa, and lower response in Klebsiella pneumoniae with New Delhi metallo-beta-lactamase 1 (NDM-1) and extended-spectrum β-lactamase (ESBL) mechanisms of resistance. In successful cases, 70% of decolonization cases occurred within the first week after FMT. Few temporary adverse events were identified. Despite the limitations of the included studies, evidence from this review indicates a potential benefit of FMT as a decolonization intervention, which can only be confirmed by future well-designed RCTs.}, }
@article {pmid30925514, year = {2019}, author = {Lukovic, E and Moitra, VK and Freedberg, DE}, title = {The microbiome: implications for perioperative and critical care.}, journal = {Current opinion in anaesthesiology}, volume = {32}, number = {3}, pages = {412-420}, doi = {10.1097/ACO.0000000000000734}, pmid = {30925514}, issn = {1473-6500}, mesh = {Analgesics, Opioid/administration &amp; dosage/adverse effects ; Anti-Bacterial Agents/administration &amp; dosage/adverse effects ; Critical Care/*methods ; Critical Illness/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Perioperative Care/adverse effects/*methods ; Postoperative Complications/etiology/physiopathology/*prevention &amp; control ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; Stress, Psychological/physiopathology ; Surgical Procedures, Operative/*adverse effects ; }, abstract = {PURPOSE OF REVIEW: The host-microbiota relationship is integral in human health and can be rapidly disrupted in ways that may contribute to poor recovery from surgery or acute illness. We review key studies by organ system to understand the effect of perioperative and critical illness stress on the microbiota. Throughout the review, our focus is on potential interventions that may be mediated by the microbiome.<br><br>RECENT FINDINGS: Although any perioperative intervention can have a profound impact on the gut microbiota, it is less clear how such changes translate into altered health outcomes. Preoperative stress (anxiety, lack of sleep, fasting), intraoperative stress (surgery itself, volatile anesthetics, perioperative antibiotics, blood transfusions), and postoperative stress (sepsis, surgical site infections, acute respiratory distress syndrome, catecholamines, antibiotics, opioids, proton pump inhibitors) have all been associated with alterations of the commensal microflora. These factors (e.g. administration of antibiotics or opioids) can create a favorable environment for emergence of pathogen virulence and development of serious infections and multiorgan failure. Data to recommend therapies aimed at restoring a disrupted microbiota, such as probiotics/prebiotics and fecal microbiota transplants is currently scarce.<br><br>SUMMARY: The microbiome is likely to play an important role in the perioperative and ICU setting but existing data is largely descriptive. There is an expanding number of mechanistic studies that attempt to disentangle the complicated bi-directional relationship between the host and the resident microbiota. When these results are combined with ongoing clinical studies, we should be able to offer better therapies aimed at restoring the microbiota in the future.}, }
@article {pmid30924853, year = {2019}, author = {Suzumura, EA and Bersch-Ferreira, &#xc2;C and Torreglosa, CR and da Silva, JT and Coqueiro, AY and Kuntz, MGF and Chrispim, PP and Weber, B and Cavalcanti, AB}, title = {Effects of oral supplementation with probiotics or synbiotics in overweight and obese adults: a systematic review and meta-analyses of randomized trials.}, journal = {Nutrition reviews}, volume = {77}, number = {6}, pages = {430-450}, doi = {10.1093/nutrit/nuz001}, pmid = {30924853}, issn = {1753-4887}, mesh = {Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Body Mass Index ; Body Weight ; Female ; Humans ; Male ; Middle Aged ; Obesity/*drug therapy ; Overweight/*drug therapy ; Probiotics/*administration &amp; dosage/pharmacology ; Randomized Controlled Trials as Topic ; Synbiotics/*administration &amp; dosage ; Waist Circumference ; Young Adult ; }, abstract = {CONTEXT: Recent evidence suggests that modulation of the gut microbiota may contribute to body weight control.<br><br>OBJECTIVE: This systematic review aimed to assess the effects of oral supplementation with probiotics or synbiotics on body weight, body mass index (BMI), and waist circumference in overweight and obese adults (BMI &#x2265;&#x2005;25&#x2009;kg/m2).<br><br>DATA SOURCES: Five electronic databases-PubMed, Embase, Cochrane Library/CENTRAL, LILACS, and Web of Science-were searched from inception to August 2017. No language restrictions were applied.<br><br>STUDY SELECTION: Randomized and quasi-randomized parallel trials that assessed the effects of oral supplementation with probiotics or synbiotics vs any other intervention but bariatric surgery or fecal transplantation in overweight or obese adults were selected.<br><br>DATA EXTRACTION: Three teams of 2 authors independently assessed risk of bias and extracted data from the included trials. Data were pooled using inverse-variance random-effects meta-analyses. The quality of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.<br><br>RESULTS: Nineteen randomized trials (28 publications, 1412 participants) were included. There were no differences in mean body weight change [mean difference (MD), -0.54&#x2009;kg; 95%CI, -1.09 to 0.01; I2&#x2009;=&#x2009;0%; moderate quality of evidence) or mean BMI change (MD, -0.19&#x2009;kg/m2; 95%CI, -0.43 to 0.04; I2&#x2009;=&#x2009;51%; low quality of evidence) between groups who received probiotics or synbiotics and control groups. Oral supplementation with probiotics or synbiotics reduced mean waist circumference compared with control (MD, -0.82&#x2009;cm; 95%CI, -1.43 to -0.21; I2&#x2009;=&#x2009;46%; low quality of evidence).<br><br>CONCLUSIONS: The findings suggest that oral supplementation with probiotics or synbiotics has a small effect to reduce waist circumference but no effect on body weight or BMI, although the quality of evidence is low to moderate. Therefore, the current evidence is not definitive. Large-scale trials are needed and may help to better inform clinical practice.<br><br>PROSPERO registration number CRD42018075126.}, }
@article {pmid30922964, year = {2019}, author = {Liao, X and Song, L and Zeng, B and Liu, B and Qiu, Y and Qu, H and Zheng, Y and Long, M and Zhou, H and Wang, Y and Du, Y and Xu, J and Shen, R and Tong, Q and Cai, L and Li, X and Guo, S and Yang, G and Zhu, Z and Pu, X and Wei, H and Zheng, H}, title = {Alteration of gut microbiota induced by DPP-4i treatment improves glucose homeostasis.}, journal = {EBioMedicine}, volume = {44}, number = {}, pages = {665-674}, pmid = {30922964}, issn = {2352-3964}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Blood Glucose ; Diabetes Mellitus, Type 2/metabolism ; Diet, High-Fat ; Dipeptidyl-Peptidase IV Inhibitors/*pharmacology ; Disease Models, Animal ; Gastrointestinal Microbiome/*drug effects ; Glucose/*metabolism ; Glucose Tolerance Test ; Homeostasis/*drug effects ; Humans ; Insulin/metabolism ; Male ; Metagenome ; Metagenomics/methods ; Mice ; }, abstract = {BACKGROUND: Increasing evidence indicates that the gut microbiota contributes to the occurrence and development of metabolic diseases. However, little is known about the effects of commonly used antidiabetic agents on the gut microbiota. In this study, we investigated the roles of dipeptidyl peptidase-4 inhibitors (DPP-4i) and α-glucosidase inhibitor in modulating the gut microbiota.<br><br>METHODS: 16S-rDNA sequencing was performed to analyse the effects of DPP-4i and acarbose on the gut microbiota in mice fed a high-fat diet (HFD). Fecal microbiota transplantation (FMT) from type 2 diabetes patients to germ-free mice was performed to investigate the contribution of the altered microbiome to antidiabetic effects of the drugs. Fecal metabolomics was also analysed by untargeted and targeted GC-MS systems.<br><br>FINDINGS: Although DPP-4i and &#x3b1;-glucosidase inhibitor both altered the gut microbial composition, only the microbiome modulation of DPP-4i contributed to its hypoglycemic effect. Specifically, the changes of 68.6% genera induced by HFD were rescued by DPP-4i. FMT showed that the DPP-4i-altered microbiome improved glucose tolerance in colonized mice, while acarbose did not. Moreover, DPP-4i increased the abundance of Bacteroidetes, and also promoted a functional shift in the gut microbiome, especially increasing the production of succinate.<br><br>INTERPRETATION: Our findings demonstrate an important effect of DPP-4i on the gut microbiota, revealing a new hypoglycemic mechanism and an additional benefit of it. Furthermore, modulating the microbial composition, and the functional shift arising from changes in the microbiome, might be a potential strategy for improving glucose homeostasis. FUND: This work was supported by grants from the National Natural Science Foundation of China (No. 81700757, No. 81471039, No. 81700714 and No. 81770434), the National Key R&amp;D Program of China (No. 2017YFC1309602, No. 2016YFC1101100, No. 2017YFD0500503 and No. 2017YFD0501001), and the Natural Science Foundation of Chongqing (No. cstc2014jcyjjq10006, No. cstc2016jcyjA0093 and No. cstc2016jcyjA0518).}, }
@article {pmid30920413, year = {2019}, author = {Bajaj, JS and Hays, RA}, title = {Manipulation of the Gut-Liver Axis Using Microbiome Restoration Therapy in Primary Sclerosing Cholangitis.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {7}, pages = {1027-1029}, doi = {10.14309/ajg.0000000000000191}, pmid = {30920413}, issn = {1572-0241}, mesh = {*Cholangitis, Sclerosing ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Liver ; *Microbiota ; }, abstract = {Alteration of the normal gut-liver axis is important in primary sclerosing cholangitis (PSC). Lack of effective medical therapy for PSC makes microbiome restoration an alluring therapeutic target. Allegretti et al. performed an open-label safety trial of fecal microbiota transplant (FMT) in noncirrhotic PSC patients with inflammatory bowel disease in remission on minimal therapy. FMT was safe in this population, and after FMT, there was a stable, early increase in microbial diversity and donor engraftment with mixed effects on alkaline phosphatase but no significant change in fecal bile acid profile. Further trials are needed to find whether FMT has a role to play in PSC therapy.}, }
@article {pmid30919462, year = {2019}, author = {Matsuo, K and Haku, A and Bi, B and Takahashi, H and Kamada, N and Yaguchi, T and Saijo, S and Yoneyama, M and Goto, Y}, title = {Fecal microbiota transplantation prevents Candida albicans from colonizing the gastrointestinal tract.}, journal = {Microbiology and immunology}, volume = {63}, number = {5}, pages = {155-163}, doi = {10.1111/1348-0421.12680}, pmid = {30919462}, issn = {1348-0421}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage/pharmacology ; *Bacteria/drug effects ; Candida albicans/*pathogenicity ; Candidiasis/*prevention &amp; control ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Gastrointestinal Tract/*microbiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Symbiosis ; }, abstract = {Gut microbes symbiotically colonize the gastrointestinal (GI) tract, interacting with each other and their host to maintain GI tract homeostasis. Recent reports have shown that gut microbes help protect the gut from colonization by pathogenic microbes. Here, we report that commensal microbes prevent colonization of the GI tract by the pathogenic fungus, Candida albicans. Wild-type specific pathogen-free (SPF) mice are resistant to C. albicans colonization of the GI tract. However, administering certain antibiotics to SPF mice enables C. albicans colonization. Quantitative kinetics of commensal bacteria are inversely correlated with the number of C. albicans in the gut. Here, we provide further evidence that transplantation of fecal microbiota is effective in preventing Candida colonization of the GI tract. These data demonstrate the importance of commensal bacteria as a barrier for the GI tract surface and highlight the potential clinical applications of commensal bacteria in preventing pathogenic fungal infections.}, }
@article {pmid30919208, year = {2019}, author = {Adler, E and Tabaa, A and Kassam, Z and Zydek, M and Terdiman, J and El-Nachef, N}, title = {Capsule-Delivered Fecal Microbiota Transplant Is Safe and Well Tolerated in Patients with Ulcerative Colitis.}, journal = {Digestive diseases and sciences}, volume = {64}, number = {9}, pages = {2452-2454}, pmid = {30919208}, issn = {1573-2568}, mesh = {Adult ; Aged ; Capsules ; Colitis, Ulcerative/*therapy ; Colonoscopy ; Fecal Microbiota Transplantation/*adverse effects/*methods ; Female ; Humans ; Male ; Middle Aged ; Patient Acceptance of Health Care ; Prospective Studies ; Severity of Illness Index ; }, }
@article {pmid30918795, year = {2019}, author = {Yatsonsky Ii, D and Pan, K and Shendge, VB and Liu, J and Ebraheim, NA}, title = {Linkage of microbiota and osteoporosis: A mini literature review.}, journal = {World journal of orthopedics}, volume = {10}, number = {3}, pages = {123-127}, pmid = {30918795}, issn = {2218-5836}, abstract = {The gut microbiota (GM) has become a recent topic of interest in the role of many disease states. Assessing patients with osteoporosis (OP), there is a strong correlation between gut microbe dysregulation and decreased bone density. Gut dysbiosis may lead to inflammation, dysregulation of nutrient and calcium transport across the intestine into circulation and systemic inflammation. Investigation of microbial profile relative to normal gut microbiomes, assessment of inflammatory markers such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha. Therapies to normalize GM in patients with OP or prevent occurrence of OP to be investigated include: High fiber prebiotic diets to promote growth of normal gut bacteria and short chain fatty acid production, Probiotics to encourage growth of normal gut microbes, and antibiotic treatment followed by fecal matter transplant.}, }
@article {pmid30916575, year = {2019}, author = {Khandelwal, P and Andersen, H and Romick-Rosendale, L and Taggart, CB and Watanabe, M and Lane, A and Dandoy, CE and Lake, KE and Litts, BA and Morrow, AL and Lee, ML and Haslam, DB and Davies, SM}, title = {A Pilot Study of Human Milk to Reduce Intestinal Inflammation After Bone Marrow Transplant.}, journal = {Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine}, volume = {14}, number = {3}, pages = {193-202}, doi = {10.1089/bfm.2018.0199}, pmid = {30916575}, issn = {1556-8342}, mesh = {Animals ; Bacteremia/epidemiology/prevention &amp; control ; Bone Marrow Transplantation/*adverse effects ; Child, Preschool ; Cytokines/metabolism ; *Enteral Nutrition ; Female ; Gastrointestinal Microbiome ; Graft vs Host Disease/epidemiology/prevention &amp; control ; Humans ; Infant ; Inflammation/*prevention &amp; control ; Intestines/microbiology/*pathology ; Male ; *Milk, Human ; Ohio ; Pilot Projects ; Wound Healing ; }, abstract = {OBJECTIVE: Human milk administration in the early peritransplant period would lower intestinal inflammation after bone marrow transplant (BMT).<br><br>MATERIALS AND METHODS: Children 0-5 years undergoing BMT received either a ready-to-feed human milk preparation designed for these children (Prolacta Bioscience, Duarte, CA) or standard formula. Babies breastfeeding at the time of BMT were also enrolled on the human milk arm. Human milk was administered from day -3 until day +14 after BMT. Metagenomic shotgun sequencing and metabolomics of stool, plasma cytokines, and regenerating islet-derived 3&#x3b1; (REG3&#x3b1;) levels were measured at enrollment and day +14. Human leukocyte antigen-DR isotype (HLA-DR), CD38, and CD69 expression on T cells were evaluated at day +21.<br><br>RESULTS: Forty-six children were enrolled, 32 received human milk (donor milk n&#x2009;=&#x2009;23, breastfeeding babies n&#x2009;=&#x2009;9), and 14 were controls who received standard feeds supervised by a BMT dietician. Twenty-four patients received at least 60% of goal human milk and were evaluable. Plasma interleukin (IL)-8 (p&#x2009;=&#x2009;0.04), IL-10 (p&#x2009;=&#x2009;0.02), and REG3&#x3b1; (p&#x2009;=&#x2009;0.03) were decreased in the human milk cohort. Peripheral blood CD69[+] CD8[+] T cells were higher in controls (p&#x2009;=&#x2009;0.01). Species abundance of Adenovirus (p&#x2009;=&#x2009;0.00034), Escherichia coli (p&#x2009;=&#x2009;0.0017), Cryptosporidium parvum (p&#x2009;=&#x2009;0.0006), Dialister invisus (p&#x2009;=&#x2009;0.01), and Pseudomonas aeruginosa (p&#x2009;=&#x2009;0.05) from stool was higher in controls. Stool alanine, tyrosine, methionine, and the ratio of fecal alanine to choline and phosphocholine were higher in controls (p&#x2009;<&#x2009;0.05). No difference was observed in stool propionate and butyrate levels as measures of short-chain fatty acids between the two cohorts.<br><br>CONCLUSIONS: Administration of human milk resulted in decreased markers of intestinal inflammation and could be a valuable adjunct for patients after BMT.}, }
@article {pmid30911125, year = {2019}, author = {Velazquez, EM and Nguyen, H and Heasley, KT and Saechao, CH and Gil, LM and Rogers, AWL and Miller, BM and Rolston, MR and Lopez, CA and Litvak, Y and Liou, MJ and Faber, F and Bronner, DN and Tiffany, CR and Byndloss, MX and Byndloss, AJ and Bäumler, AJ}, title = {Endogenous Enterobacteriaceae underlie variation in susceptibility to Salmonella infection.}, journal = {Nature microbiology}, volume = {4}, number = {6}, pages = {1057-1064}, pmid = {30911125}, issn = {2058-5276}, support = {R25 GM056765/GM/NIGMS NIH HHS/United States ; R56 AI112949/AI/NIAID NIH HHS/United States ; T32 AI060555/AI/NIAID NIH HHS/United States ; R01 AI044170/AI/NIAID NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; R01 AI112949/AI/NIAID NIH HHS/United States ; T35 OD010956/OD/NIH HHS/United States ; R01 AI112445/AI/NIAID NIH HHS/United States ; T32 OD010931/OD/NIH HHS/United States ; R01 AI096528/AI/NIAID NIH HHS/United States ; }, mesh = {Animal Experimentation ; Animals ; Biomarkers ; Biosynthetic Pathways ; Disease Models, Animal ; Enterobacteriaceae/classification/*physiology ; Escherichia coli/physiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Germ-Free Life ; Mice ; Mice, Inbred C57BL ; Microbial Interactions/*physiology ; Phenotype ; Probiotics ; Reproducibility of Results ; Salmonella ; Salmonella Infections, Animal/*microbiology ; }, abstract = {Lack of reproducibility is a prominent problem in biomedical research. An important source of variation in animal experiments is the microbiome, but little is known about specific changes in the microbiota composition that cause phenotypic differences. Here, we show that genetically similar laboratory mice obtained from four different commercial vendors exhibited marked phenotypic variation in their susceptibility to Salmonella infection. Faecal microbiota transplant into germ-free mice replicated donor susceptibility, revealing that variability was due to changes in the gut microbiota composition. Co-housing of mice only partially transferred protection against Salmonella infection, suggesting that minority species within the gut microbiota might confer this trait. Consistent with this idea, we identified endogenous Enterobacteriaceae, a low-abundance taxon, as a keystone species responsible for variation in the susceptibility to Salmonella infection. Protection conferred by endogenous Enterobacteriaceae could be modelled by inoculating mice with probiotic Escherichia coli, which conferred resistance by using its aerobic metabolism to compete with Salmonella for resources. We conclude that a mechanistic understanding of phenotypic variation can accelerate development of strategies for enhancing the reproducibility of animal experiments.}, }
@article {pmid30909689, year = {2019}, author = {Kim, KO and Gluck, M}, title = {Fecal Microbiota Transplantation: An Update on Clinical Practice.}, journal = {Clinical endoscopy}, volume = {52}, number = {2}, pages = {137-143}, pmid = {30909689}, issn = {2234-2400}, abstract = {Fecal microbiota transplantation (FMT) is an infusion in the colon, or the delivery through the upper gastrointestinal tract, of stool from a healthy donor to a recipient with a disease believed to be related to an unhealthy gut microbiome. FMT has been successfully used to treat recurrent Clostridium difficile infection (rCDI). The short-term success of FMT in rCDI has led to investigations of its application to other gastrointestinal disorders and extra-intestinal diseases with presumed gut dysbiosis. Despite the promising results of FMT in these conditions, several barriers remain, including determining the characteristics of a healthy microbiome, ensuring the safety of the recipient with respect to long-term outcomes, adequate monitoring of the recipient of fecal material, achieving high-quality control, and maintaining reasonable costs. For these reasons, establishing uniform protocols for stool preparation, finding the best modes of FMT administration, maintaining large databases of donors and recipients, and assuring that oral ingestion is equivalent to the more widely accepted colonoscopic infusion are issues that need to be addressed.}, }
@article {pmid30908299, year = {2019}, author = {Xu, D and Chen, VL and Steiner, CA and Berinstein, JA and Eswaran, S and Waljee, AK and Higgins, PDR and Owyang, C}, title = {Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {7}, pages = {1043-1050}, pmid = {30908299}, issn = {1572-0241}, support = {P30 DK034933/DK/NIDDK NIH HHS/United States ; R01 DK058913/DK/NIDDK NIH HHS/United States ; T32 DK094775/DK/NIDDK NIH HHS/United States ; R01 DK110436/DK/NIDDK NIH HHS/United States ; T32 DK062708/DK/NIDDK NIH HHS/United States ; }, mesh = {Fecal Microbiota Transplantation/*methods ; Female ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/diagnosis/psychology/*therapy ; Male ; Prognosis ; *Quality of Life ; Randomized Controlled Trials as Topic ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {OBJECTIVES: Irritable bowel syndrome (IBS) is a common gastrointestinal condition with a heterogeneous pathophysiology. An altered gut microbiome has been identified in some IBS patients, and fecal microbiota transplantation (FMT) has been suggested to treat IBS. We performed meta-analyses and systematic review of available randomized controlled trials (RCTs) to evaluate the efficacy of FMT in IBS.<br><br>METHODS: We performed a systematic literature search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Selection criteria included RCTs of FMT vs placebo using FMT excipients or autologous FMT in IBS. Meta-analyses were conducted to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs) of combined studies for primary outcome of improvement in global IBS symptoms as measured by accepted integrative symptom questionnaires or dichotomous responses to questions of overall symptom improvement.<br><br>RESULTS: Among 742 citations identified, 7 were deemed to be potentially relevant, of which 4 studies involving 254 participants met eligibility. No significant difference in global improvement of IBS symptoms was observed at 12 weeks in FMT vs placebo (RR = 0.93; 95% CI 0.48-1.79). Heterogeneity among studies was significant (I = 79%). Subgroup analyses revealed benefits of single-dose FMT using colonoscopy and nasojejunal tubes in comparison with autologous FMT for placebo treatment (number needed to treat = 5, RR = 1.59; 95% CI 1.06-2.39; I = 0%) and a reduction in likelihood of improvement of multiple-dose capsule FMT RCTs (number needed to harm = 3, RR = 0.54; 95% CI 0.34-0.85; I = 13%). Placebo response was 33.7% in nonoral FMT RCTs and 67.8% in capsule FMT RCTs. The Grading of Recommendations Assessment, Development and Evaluation quality of the body of evidence was very low.<br><br>DISCUSSION: Current evidence from RCTs does not suggest a benefit of FMT for global IBS symptoms. There remain questions regarding the efficacy of FMT in IBS as well as the lack of a clean explanation on the discrepant results among RCTs in subgroup analyses.}, }
@article {pmid30906449, year = {2019}, author = {Zhou, J and Zhou, Z and Ji, P and Ma, M and Guo, J and Jiang, S}, title = {Effect of fecal microbiota transplantation on experimental colitis in mice.}, journal = {Experimental and therapeutic medicine}, volume = {17}, number = {4}, pages = {2581-2586}, pmid = {30906449}, issn = {1792-0981}, abstract = {The aim of the present study was to investigate the effect of fecal microbiota transplantation (FMT) on the acute inflammatory response in a murine model of dextran sulfate sodium (DSS)-induced colitis, and to delineate the putative underlying mechanism(s). Mice were divided into four groups, namely the normal control, DSS, 5-aminosalicylic acid (5-ASA) and FMT group. Mice in the DSS, 5-ASA and FMT groups were orally administered 3% DSS (w/v) solution for 7 days to induce colitis. On days 1, 3, 5 and 7, mice in the DSS, 5-ASA and FMT groups were respectively administered 0.5% carboxymethylcellulose sodium, 5-ASA suspension and fecal suspension by enema. The disease activity index of each mouse was calculated on a daily basis. All mice were sacrificed on day 8, and the length of their colons was measured. Myeloperoxidase (MPO) activity, and the levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-10 in the colon tissues of each group were also measured. Compared with that in the DSS group, FMT ameliorated the severity of inflammation due to ulcerative colitis in mice, which was accompanied by a significantly decreased MPO activity, reduced levels of TNF-α and IL-1β, and an increased level of IL-10 in colon tissue (all P<0.05). Taken together, these results demonstrated that FMT exerted a therapeutic effect on experimental colitis in mice, and the associated mechanism is likely to involve the remodeling of the intestinal flora and regulation of intestinal T-cell immunity homeostasis.}, }
@article {pmid30906424, year = {2019}, author = {Levy, AN and Allegretti, JR}, title = {Insights into the role of fecal microbiota transplantation for the treatment of inflammatory bowel disease.}, journal = {Therapeutic advances in gastroenterology}, volume = {12}, number = {}, pages = {1756284819836893}, pmid = {30906424}, issn = {1756-283X}, abstract = {Fecal microbiota transplantation (FMT) has changed the treatment landscape of Clostridium difficile infection (CDI). Emerging evidence has shown that FMT can also be an effective and safe treatment strategy in CDI with underlying inflammatory bowel disease (IBD). Recently, randomized controlled trials of FMT in ulcerative colitis support its expanding role in restoring gut homeostasis in this disease. However, heterogeneous study designs leave several questions yet to be answered, including how to best position this novel therapy in the treatment approach of Crohn's disease and pouchitis. Additional studies are needed to validate whether FMT can assume a complementary role in the standard treatment of IBD.}, }
@article {pmid30905818, year = {2019}, author = {Wu, X and Zhang, T and Chen, X and Ji, G and Zhang, F}, title = {Microbiota transplantation: Targeting cancer treatment.}, journal = {Cancer letters}, volume = {452}, number = {}, pages = {144-151}, doi = {10.1016/j.canlet.2019.03.010}, pmid = {30905818}, issn = {1872-7980}, mesh = {Drug Therapy/methods ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Immunotherapy/methods ; Neoplasms/*therapy ; Radiotherapy/methods ; }, abstract = {Mounting evidence have demonstrated that gut microbiota plays a critical role in cancer patients' therapeutic responses to chemotherapy, radiotherapy and immunotherapy, including clinical efficacy and sensitivity to toxicity. These fascinating findings evoke a possibility of manipulating gut microbiota to optimize anti-cancer treatment from bench to beside. Microbiota transplantation (MT), including fecal microbiota transplantation (FMT) and selective microbiota transplantation (SMT), may improve the effect of anti-cancer treatment and/or reduce the related side effects. The safety and efficacy of MT in cancer treatment are the core of translational research in this promising field, which inspire us to focus on the MT technology and mechanism of MT targeting anti-cancer treatment. To perform clean FMT based on automatic methods by machine in exclusive laboratory has become true. Colonic transendoscopic enteral tubing as a novel delivering way for MT should bring convenience for frequent delivering in practice and feasible tool for confirming the therapeutic effect in research. The present review focuses on the recent findings on role of microbiota on chemotherapy, radiotherapy and immunotherapy, and the methodology, feasibility and challenges of MT in anti-cancer treatment.}, }
@article {pmid30900526, year = {2019}, author = {Dalzell, AM and Ba'Ath, ME}, title = {Paediatric inflammatory bowel disease: review with a focus on practice in low- to middle-income countries.}, journal = {Paediatrics and international child health}, volume = {39}, number = {1}, pages = {48-58}, doi = {10.1080/20469047.2019.1575056}, pmid = {30900526}, issn = {2046-9055}, mesh = {Adolescent ; Child ; Child, Preschool ; Colonoscopy ; Developing Countries ; *Disease Management ; Endoscopy, Digestive System ; Histocytochemistry ; Humans ; Infant ; Inflammatory Bowel Diseases/*diagnosis/epidemiology/pathology/*therapy ; Prevalence ; }, abstract = {Inflammatory bowel disease (IBD) should be considered in any child with a persistently altered bowel habit. Growth failure may be a consequence and there may also be extra-intestinal manifestations. Oesophago-gastroduodenoscopy and colonoscopy and conventional histopathology are the diagnostic tools of choice in IBD. The identification and management of children with IBD in resource-poor settings is difficult and there are few data on its prevalence in low- and middle-income countries. The main challenges are a lack of resources and infrastructure including trained personnel in settings where there are other priorities for maintaining the health and wellbeing of children. The identification and management of children with inflammatory bowel conditions often depends on the enthusiasm, skill and commitment of a few dedicated individuals. Abbreviations: ADA: Adalimumab; CD: Crohn disease; ECCO: European Crohn's and Colitis Organisation; EEN: exclusive enteral nutrition; ESPGHAN: European Society for Paediatric Gastroenterology Hepatology and Nutrition; FMT: faecal microbiota transplantation; GDP: gross domestic product; HIC: high-income countries; IBD: inflammatory bowel disease; IBDU: inflammatory bowel disease unclassified; IC: ileocolonoscopy; IFX: infliximab; IPAA: ileal pouch anal anastomosis; LMIC: low- and middle-income countries; MH: mucosal healing; OGD: oesophago-gastroduodenoscopy; PCDAI: Paediatric Crohn's Disease Activity Index; PIBD: paediatric inflammatory bowel disease; PUCAI: Paediatric Ulcerative Colitis Activity Index; UC: ulcerative colitis; UGIT: upper gastrointestinal tract; VEO-IBD: very early-onset IBD; WLE: white light endoscopy; 5-ASA: 5 aminosalicylic acid; 6-MP: 6-mercaptopurine.}, }
@article {pmid30899209, year = {2019}, author = {Fischer, M}, title = {Recent Research on Fecal Microbiota Transplantation in Inflammatory Bowel Disease Patients.}, journal = {Gastroenterology &amp; hepatology}, volume = {15}, number = {1}, pages = {44-47}, pmid = {30899209}, issn = {1554-7914}, }
@article {pmid30899006, year = {2019}, author = {Wang, W and Lin, L and Du, Y and Song, Y and Peng, X and Chen, X and Yang, CJ}, title = {Assessing the viability of transplanted gut microbiota by sequential tagging with D-amino acid-based metabolic probes.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {1317}, pmid = {30899006}, issn = {2041-1723}, mesh = {Amino Acids/*administration &amp; dosage/chemistry ; Animals ; Anti-Bacterial Agents/pharmacology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Fluorescent Dyes/chemistry ; Gastrointestinal Microbiome/*drug effects/genetics ; Gastrointestinal Tract/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Microbial Viability/drug effects ; RNA, Ribosomal, 16S/*genetics ; Staining and Labeling/*methods ; Stereoisomerism ; }, abstract = {Currently, there are more than 200 fecal microbiota transplantation (FMT) clinical trials worldwide. However, our knowledge of this microbial therapy is still limited. Here we develop a strategy using sequential tagging with D-amino acid-based metabolic probes (STAMP) for assessing the viabilities of transplanted microbiotas. A fluorescent D-amino acid (FDAA) is first administered to donor mice to metabolically label the gut microbiotas in vivo. The labeled microbiotas are transplanted to recipient mice, which receive a second FDAA with a different color. The surviving transplants should incorporate both FDAAs and can be readily distinguished by presenting two colors simultaneously. Isolation of surviving bacteria and 16S rDNA sequencing identify several enriched genera, suggesting the importance of specific bacteria in FMT. In addition, using STAMP, we evaluate the effects on transplant survival of pre-treating recipients using different antibiotics. We propose STAMP as a versatile tool for deciphering the complex biology of FMT, and potentially improving its treatment efficacy.}, }
@article {pmid30898652, year = {2019}, author = {O'Connor, KM and Lucking, EF and Golubeva, AV and Strain, CR and Fouhy, F and Cenit, MC and Dhaliwal, P and Bastiaanssen, TFS and Burns, DP and Stanton, C and Clarke, G and Cryan, JF and O'Halloran, KD}, title = {Manipulation of gut microbiota blunts the ventilatory response to hypercapnia in adult rats.}, journal = {EBioMedicine}, volume = {44}, number = {}, pages = {618-638}, pmid = {30898652}, issn = {2352-3964}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage/adverse effects ; Biomarkers ; Blood Gas Analysis ; Brain Stem/metabolism/physiopathology ; Breath Tests ; Cell Membrane Permeability ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; Heart Function Tests ; Heart Rate ; Hypercapnia/blood/*etiology/*physiopathology ; Hypoxia/metabolism ; Intestinal Mucosa/metabolism ; Male ; Metagenome ; Metagenomics/methods ; Rats ; Receptors, Serotonin, 5-HT3/metabolism ; *Respiration ; }, abstract = {BACKGROUND: It is increasingly evident that perturbations to the diversity and composition of the gut microbiota have significant consequences for the regulation of integrative physiological systems. There is growing interest in the potential contribution of microbiota-gut-brain signalling to cardiorespiratory control in health and disease.<br><br>METHODS: In adult male rats, we sought to determine the cardiorespiratory effects of manipulation of the gut microbiota following a 4-week administration of a cocktail of antibiotics. We subsequently explored the effects of administration of faecal microbiota from pooled control (vehicle) rat faeces, given by gavage to vehicle- and antibiotic-treated rats.<br><br>FINDINGS: Antibiotic intervention depressed the ventilatory response to hypercapnic stress in conscious animals, owing to a reduction in the respiratory frequency response to carbon dioxide. Baseline frequency, respiratory timing variability, and the expression of apnoeas and sighs were normal. Microbiota-depleted rats had decreased systolic blood pressure. Faecal microbiota transfer to vehicle- and antibiotic-treated animals also disrupted the gut microbiota composition, associated with depressed ventilatory responsiveness to hypercapnia. Chronic antibiotic intervention or faecal microbiota transfer both caused significant disruptions to brainstem monoamine neurochemistry, with increased homovanillic acid:dopamine ratio indicative of increased dopamine turnover, which correlated with the abundance of several bacteria of six different phyla.<br><br>INTERPRETATION: Chronic antibiotic administration and faecal microbiota transfer disrupt gut microbiota, brainstem monoamine concentrations and the ventilatory response to hypercapnia. We suggest that aberrant microbiota-gut-brain axis signalling has a modulatory influence on respiratory behaviour during hypercapnic stress. FUND: Department of Physiology and APC Microbiome Ireland, University College Cork, Ireland.}, }
@article {pmid30898649, year = {2019}, author = {Papanicolas, LE and Wesselingh, SL and Rogers, GB}, title = {Do we really understand how faecal microbiota transplantation works? Authors' reply.}, journal = {EBioMedicine}, volume = {42}, number = {}, pages = {40}, pmid = {30898649}, issn = {2352-3964}, mesh = {*Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid30897248, year = {2019}, author = {Alrafas, HR and Busbee, PB and Nagarkatti, M and Nagarkatti, PS}, title = {Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells.}, journal = {Journal of leukocyte biology}, volume = {106}, number = {2}, pages = {467-480}, pmid = {30897248}, issn = {1938-3673}, support = {R01 AI129788/AI/NIAID NIH HHS/United States ; R01 MH094755/MH/NIMH NIH HHS/United States ; P20 GM103641/GM/NIGMS NIH HHS/United States ; P01 AT003961/AT/NCCIH NIH HHS/United States ; R01 AT006888/AT/NCCIH NIH HHS/United States ; R01 AI123947/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Biomarkers ; Colitis/*etiology/metabolism/pathology/prevention &amp; control ; Colonoscopy ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/*immunology ; Humans ; Immunomodulation/*drug effects ; Metagenomics/methods ; Mice ; Resveratrol/*pharmacology ; T-Lymphocyte Subsets/immunology/metabolism ; T-Lymphocytes, Regulatory/drug effects/*immunology/metabolism ; Th17 Cells/drug effects/*immunology/metabolism ; }, abstract = {Inflammatory diseases of the gastrointestinal tract are often associated with microbial dysbiosis. Thus, dietary interactions with intestinal microbiota, to maintain homeostasis, play a crucial role in regulation of clinical disorders such as colitis. In the current study, we investigated if resveratrol, a polyphenol found in a variety of foods and beverages, would reverse microbial dysbiosis induced during colitis. Administration of resveratrol attenuated colonic inflammation and clinical symptoms in the murine model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Resveratrol treatment in mice with colitis led to an increase in CD4[+] FOXP3[+] and CD4[+] IL-10[+] T cells, and a decrease in CD4[+] IFN-γ[+] and CD4[+] IL-17[+] T cells. 16S rRNA gene sequencing to investigate alterations in the gut microbiota revealed that TNBS caused significant dysbiosis, which was reversed following resveratrol treatment. Analysis of cecal flush revealed that TNBS administration led to an increase in species such as Bacteroides acidifaciens, but decrease in species such as Ruminococcus gnavus and Akkermansia mucinphilia, as well as a decrease in SCFA i-butyric acid. However, resveratrol treatment restored the gut bacteria back to homeostatic levels, and increased production of i-butyric acid. Fecal transfer experiments confirmed the protective role of resveratrol-induced microbiota against colitis inasmuch as such recipient mice were more resistant to TNBS-colitis and exhibited polarization toward CD4[+] FOXP3[+] T cells and decreases in CD4[+] IFN-γ[+] and CD4[+] IL-17[+] T cells. Collectively, these data demonstrate that resveratrol-mediated attenuation of colitis results from reversal of microbial dysbiosis induced during colitis and such microbiota protect the host from colonic inflammation by inducing Tregs while suppressing inflammatory Th1/Th17 cells.}, }
@article {pmid30893082, year = {2019}, author = {Alsahhar, JS and Rahimi, RS}, title = {Updates on the pathophysiology and therapeutic targets for hepatic encephalopathy.}, journal = {Current opinion in gastroenterology}, volume = {35}, number = {3}, pages = {145-154}, doi = {10.1097/MOG.0000000000000527}, pmid = {30893082}, issn = {1531-7056}, mesh = {Amino Acids, Aromatic/metabolism ; Amino Acids, Branched-Chain/therapeutic use ; Ammonia/metabolism ; Dipeptides/therapeutic use ; Fecal Microbiota Transplantation/*methods ; Frailty/epidemiology ; Gastrointestinal Agents/*therapeutic use ; Gastrointestinal Microbiome ; Glycerol/analogs &amp; derivatives/therapeutic use ; Hepatic Encephalopathy/epidemiology/etiology/metabolism/*therapy ; Humans ; Hypertension, Portal/complications/metabolism ; Lactulose/therapeutic use ; Liver Cirrhosis/complications/metabolism ; Ornithine/analogs &amp; derivatives/therapeutic use ; Phenylbutyrates/therapeutic use ; Polyethylene Glycols/therapeutic use ; Probiotics/therapeutic use ; Rifaximin/therapeutic use ; Trace Elements/therapeutic use ; Zinc/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: Hepatic encephalopathy is one of the most debilitating clinical manifestations of cirrhosis and associated with increased morbidity and mortality. Treatment modalities available include the nonabsorbable disaccharides (lactulose) and the nonabsorbable antibiotics (rifaximin).<br><br>RECENT FINDINGS: Newer therapeutic targets under evaluation include ammonia scavengers (ornithine phenylacetate) and modulation of gut microbiota (fecal microbiota transplantation).<br><br>SUMMARY: This review will focus on the pathophysiology of hepatic encephalopathy along with an update on therapeutic targets under investigation.}, }
@article {pmid30891076, year = {2019}, author = {Zhang, Y and Li, Z and Zhao, Z and Kuai, W and Wei, C and Lv, J and Zhi, J and Jia, Y}, title = {Effect of the Chinese Medicine YangZheng XiaoJi on Reducing Fatigue in Mice with Orthotopic Transplantation of Colon Cancer.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2019}, number = {}, pages = {3870812}, pmid = {30891076}, issn = {1741-427X}, abstract = {BACKGROUND: Fatigue is a common, distressing, and persistent symptom for patients with malignant tumor including colorectal cancer (CRC). Although studies of cancer-related fatigue (CRF) have sprung out in recent years, the pathophysiological mechanisms that induce CRF remain unclear, and effective therapeutic interventions have yet to be established.<br><br>METHODS: To investigate the effect of the traditional Chinese medicine YangZheng XiaoJi (YZXJ) on CRF, we constructed orthotopic colon cancer mice, randomly divided into YZXJ group and control (NS) group. Physical or mental fatigue was respectively assessed by swimming exhaustion time or suspension tail resting time. At the end of the experiment, serum was collected to measure the expression level of inflammatory factors by ELISA and feces to microbiota changes by 16s rDNA, and hepatic glycogen content was detected via the anthrone method.<br><br>RESULT: The nutritional status of the YZXJ group was better than that of the control group, and there was no statistical difference in tumor weight. The swimming exhaustion times of YZXJ group and control group were (162.80 &#xb1; 14.67) s and (117.60 &#xb1; 13.42, P < 0.05) s, respectively; the suspension tail resting time of YZXJ group was shorter than that of the control group (49.85 &#xb1; 4.56) s and (68.83 &#xb1; 7.26) s, P < 0.05)). Serum levels of IL-1&#x3b2; and IL-6 in YZXJ group were significantly lower than the control group (P < 0.05). Liver glycogen in YZXJ group was (5.18 &#xb1; 3.11) mg/g liver tissue, which was significantly higher than that in control group (2.95 &#xb1; 2.06) mg/g liver tissue (P < 0.05). At phylum level, increased abundance of Bacteroidetes, Verrucomicrobia, Actinobacteria, and Cyanobacteria and decreased Proteobacteria in YZXJ group emerged as the top differences between the two groups, and the Firmicutes/Bacteroidetes ratio was decreased in YZXJ group compared to the control group. At genus level, the abundance of Parabacteroides, unidentified Saprospiraceae, and Elizabethkingia which all belong to phylum Bacteroidetes were increased, while Arcobacter, Marinobacter, Alkanindiges, Sulfuricurvum, Haliangium, and Thiobacillus in phylum Proteobacteria were decreased after YZXJ intervention. YZXJ can also increase Pirellula, Microbacterium, and Alpinimonas and decrease Rubrobacter and Iamia.<br><br>CONCLUSION: YZXJ may reduce the physical and mental fatigue caused by colorectal cancer by inhibiting inflammatory reaction, promoting hepatic glycogen synthesis, and changing the composition of intestinal microbiota.}, }
@article {pmid30890952, year = {2019}, author = {Wan, JJ and Lin, CH and Ren, ED and Su, Y and Zhu, WY}, title = {Effects of Early Intervention With Maternal Fecal Bacteria and Antibiotics on Liver Metabolome and Transcription in Neonatal Pigs.}, journal = {Frontiers in physiology}, volume = {10}, number = {}, pages = {171}, pmid = {30890952}, issn = {1664-042X}, abstract = {The establishment of a stable bacterial flora in early life is associated with host metabolism. Studies of fecal microbiota transplantation (FMT) and antibiotics on neonatal pig mainly focused on intestinal development and mucosal immunity, but the information on metabolism is lacking. The objective of this study was to investigate the responses of metabolome and transcriptome in the livers of neonatal piglets that were orally inoculated with maternal fecal bacteria suspension and amoxicillin (AM) solution. Five litters of Duroc × Landrace × Yorkshire neonatal piglets were used as five replicates and nine piglets in each litter were randomly assigned to the control (CO), AM or FMT groups. Neonatal piglets in three groups were fed with 3 mL saline (0.9%), AM solution (6.94 mg/mL) or fecal bacteria suspension (>10[9]/mL), respectively, on days 1-6. At the age of 7 and 21 days, one piglet from each group in each litter was sacrificed, and the serum and liver were collected for analysis. The RNA sequencing analysis showed that the mRNA expressions of arachidonate 12-lipoxygenase (ALOX12), acetyl-CoA acyltransferase 2 (ACAA2), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), glutamic-pyruvic transaminase 2 (GPT2) and argininosuccinate synthase 1 (ASS1) were downregulated (P < 0.05) by AM on day 7, and that the mRNA expressions of arachidonate 15-lipoxygenase (ALOX15), CYP1A2 and GPT2 were downregulated (P < 0.05) by FMT on day 7. GC-MS analysis showed that AM and FMT treatments mainly affected fatty acid metabolism and amino acid metabolism on days 7 and 21. AM and FMT both reduced (P < 0.05) the blood levels of triglycerides and low density lipoprotein cholesterol (LDL-C) on day 7. AM reduced (P < 0.05) the blood level of cholesterol on day 21, and FMT reduced the blood levels of cholesterol, triglycerides and LDL-C on day 21. These results indicate that early intervention with FMT or AM can reduce fatty acid oxidative catabolism and amino acid biosynthesis of neonatal piglets, which provides a reference for regulation host metabolism through early intervention in animal production and even human health.}, }
@article {pmid30889205, year = {2019}, author = {Ohara, T}, title = {Identification of the microbial diversity after fecal microbiota transplantation therapy for chronic intractable constipation using 16s rRNA amplicon sequencing.}, journal = {PloS one}, volume = {14}, number = {3}, pages = {e0214085}, pmid = {30889205}, issn = {1932-6203}, mesh = {Adult ; *Bacteria/classification/genetics/isolation &amp; purification ; Chronic Disease ; *Constipation/microbiology/therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; Middle Aged ; RNA, Bacterial/*genetics ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapeutic approach for the treatment of functional gastrointestinal disease by restoring gut microbiota; however, there is a lack of sufficient understanding regarding which microbial populations successfully colonize the recipient gut. This study characterized microbial composition and diversity in patients diagnosed with chronic constipation at 1 month and 1 year after FMT.<br><br>METHODS: We explored the microbial diversity of pre- and posttransplant stool specimens from patients using 16S rRNA gene sequencing, followed by functional analysis.<br><br>RESULTS: The results identified 22 species of microorganisms colonized in the recipients from the donors at 1 month after FMT. One-year follow-up of the patient identified the colonization of 18 species of microorganisms, resulting in identification of species in significant abundance, including Bacteroides fragilis and Hungatella hathewayi in the recipient at 1 month after FMT and Dialister succinatiphilus, Coprococcus catus, and Sutterella stercoricanis at 1 year after FMT. The majority of the colonized species belong to the phylum Firmicutes and carry genes related to polysaccharide metabolism and that enhance the energy-harvesting efficiency of the host.<br><br>CONCLUSION: These results suggest that FMT is effective for the treatment of chronic constipation through the restoration and colonization of donor microbiota in the recipient gut up to 1 year after FMT.}, }
@article {pmid30886607, year = {2019}, author = {Liu, Z and Wang, N and Ma, Y and Wen, D}, title = {Hydroxytyrosol Improves Obesity and Insulin Resistance by Modulating Gut Microbiota in High-Fat Diet-Induced Obese Mice.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {390}, pmid = {30886607}, issn = {1664-302X}, abstract = {Obesity is a common chronic metabolic disease that is harmful to human health and predisposes the affected individuals to a cluster of pathologies. Insulin resistance (IR) is one of the most frequent complications of obesity. Hydroxytyrosol (HT) may reduce obesity and IR in high-fat diet (HFD)-fed mice; however, the mechanism underlying is still unknown. Systemic low-grade inflammation and intestinal dysfunction are thought to be associated with obesity and IR. In this study, we found that HFD feeding for 8 weeks altered the intestinal microbiota, injured intestinal barrier function, increased endotoxin release into the blood, enhanced the expression of inflammatory factors (TNF-α, IL-1β, IL-6) and lipid accumulation in liver, caused obesity, and aggravated IR via the JNK/IRS (Ser 307) pathway in HFD mice. We also found that HT gavage could reverse those effects and the beneficial effects of HT were transferable through fecal microbiota transplantation. Our data indicate that HT can improve obesity and IR by altering the composition of the intestinal microbiota and improving integrity of the intestinal wall. We propose that HT replenishment may be used as a dietary intervention strategy to prevent obesity and IR.}, }
@article {pmid30885724, year = {2019}, author = {Quraishi, MN and McNally, A and van Schaik, W}, title = {Do we really understand how faecal microbiota transplantation works?.}, journal = {EBioMedicine}, volume = {42}, number = {}, pages = {39}, pmid = {30885724}, issn = {2352-3964}, mesh = {Bacteriophages/isolation &amp; purification ; *Fecal Microbiota Transplantation ; Feces/microbiology/virology ; Gastrointestinal Microbiome ; Humans ; Oxygen/metabolism ; }, }
@article {pmid30882536, year = {2019}, author = {Allegretti, JR and Kassam, Z and Fischer, M and Kelly, C and Chan, WW}, title = {Risk Factors for Gastrointestinal Symptoms Following Successful Eradication of Clostridium difficile by Fecal Microbiota Transplantation (FMT).}, journal = {Journal of clinical gastroenterology}, volume = {53}, number = {9}, pages = {e405-e408}, doi = {10.1097/MCG.0000000000001194}, pmid = {30882536}, issn = {1539-2031}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*therapy ; Cohort Studies ; Colonoscopy ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Diseases/*epidemiology ; Humans ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Tissue Donors/*statistics &amp; numerical data ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapy for recurrent Clostridioides difficile infection (CDI). Many patients report altered bowel habits including constipation, bloating, gas and loose stool post-FMT despite resolution of CDI, and the etiology remains unclear.<br><br>METHODS: This was a prospective cohort study of adult patients with recurrent CDI who underwent FMT (1) via colonoscopy with patient-selected donor stool, (2) via colonoscopy from a universal stool bank donor, or (3) via capsules from a universal stool bank. Reassessment occurred 8 weeks post-FMT. Those cured were assessed for gastrointestinal symptoms (bloating, loose stools, constipation). Multivariate logistic regression was performed to assess predictors of post-FMT gastrointestinal symptoms.<br><br>RESULTS: A total of 150 subjects underwent FMT for recurrent CDI, of which 68.7% (103) were female, mean age was 61.5 years&#xb1;18.1 and 31 patients (20.7%) had preexisting irritable bowel syndrome. Thirty-six had FMT via colonoscopy with a patient-selected donor, 67 via colonoscopy with stool bank donors, and 47 via FMT capsules from stool bank donors. Among those cured, 41 (31.2%) had gastrointestinal symptoms post-FMT. The factors associated with symptoms included younger age (57.2 vs. 64.1&#x2009;y, P=0.03), a baseline history of irritable bowel syndrome (36.6% vs. 13.3%, P=0.002) and preexisting inflammatory bowel disease (31.7% vs. 10%, P=0.002). Small bowel exposure to donor stool was not related to symptoms (63.4% vs. 62.2%, P=0.89).<br><br>CONCLUSIONS: Altered bowel habits are a consequence of CDI and are common after FMT. This study suggests that donor type and FMT delivery modality are not related to the presence of irregular gastrointestinal symptoms after FMT.}, }
@article {pmid30880228, year = {2019}, author = {Davido, B and Batista, R and Dinh, A and de Truchis, P and Terveer, EM and Roberts, B and Kuijper, EJ and Caballero, S}, title = {Fifty shades of graft: How to improve the efficacy of faecal microbiota transplantation for decolonization of antibiotic-resistant bacteria.}, journal = {International journal of antimicrobial agents}, volume = {53}, number = {5}, pages = {553-556}, doi = {10.1016/j.ijantimicag.2019.03.008}, pmid = {30880228}, issn = {1872-7913}, mesh = {Bacteria/*drug effects/isolation &amp; purification ; Bacterial Infections/*microbiology/*therapy ; *Drug Resistance, Bacterial ; Fecal Microbiota Transplantation/*methods ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Spontaneous decolonization of antibiotic-resistant bacteria (ARB) takes time: approximately 25% after 30 days for carbapenem-producing Enterobacteriaceae or extended-spectrum beta-lactamase-producing Enterobacteriaceae. Faecal microbiota transplantation (FMT) has been proposed as a new strategy to promote decolonization in order to reduce the risk of superinfection due to these ARB. This paper discusses the literature on the use of FMT for this indication, and the improvement levers available to promote its efficacy.<br><br>METHODS: Literature available to date concerning the use of FMT to eradicate ARB was reviewed, and the different factors that may have influenced the efficacy of decolonization were evaluated.<br><br>RESULTS: Four axes that could have played major roles in the efficacy of FMT were identified: bowel preparation before FMT; donor; dose; and thermal conditioning of faeces. The positive or negative impact of each on the outcome of FMT is discussed.<br><br>CONCLUSION: Although FMT is very efficient for the eradication of Clostridium difficile, the same 'recipe' cannot be used for the eradication of ARB. Working together with expert centres may help to improve the efficacy of FMT for this indication, and enable the reduction of in-hospital isolation precautions.}, }
@article {pmid30877020, year = {2019}, author = {Uchiyama, K and Naito, Y and Takagi, T}, title = {Intestinal microbiome as a novel therapeutic target for local and systemic inflammation.}, journal = {Pharmacology &amp; therapeutics}, volume = {199}, number = {}, pages = {164-172}, doi = {10.1016/j.pharmthera.2019.03.006}, pmid = {30877020}, issn = {1879-016X}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; Inflammation/*microbiology/therapy ; }, abstract = {Recently, the pathogenesis of systemic inflammatory disease such as inflammatory bowel disease (IBD), multiple sclerosis (MS), systemic inflammatory arthritis, asthma, and non-alcoholic fatty liver disease has been reported to be related to the dysbiosis of gut microbiota. The contribution of special bacteria for the development of those diseases has been elucidated by disease animal models such as germ-free mice. Besides, the contribution by several bacteria for the pathogenesis of those diseases has been suggested by detailed analysis of the 16 small ribosomal subunit RNA (16S rRNA) from stool samples of the patients. Gut microbiota-targeted treatment for systemic inflammatory diseases such as fecal microbiota transplant (FMT), and probiotics has been now reported. Though there are several issues to be understood, these treatments have been highlighted as an innovative approach to intractable systemic inflammatory disease. In the present review, recent reports regarding the relation between gut microbiota and systemic inflammatory diseases are discussed with treatments to target gut microbiota.}, }
@article {pmid30876614, year = {2019}, author = {Ramesh, MS and Yee, J}, title = {Clostridioides difficile Infection in Chronic Kidney Disease/End-Stage Renal Disease.}, journal = {Advances in chronic kidney disease}, volume = {26}, number = {1}, pages = {30-34}, doi = {10.1053/j.ackd.2019.01.001}, pmid = {30876614}, issn = {1548-5609}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Antibodies, Monoclonal/*therapeutic use ; Antimicrobial Stewardship ; Broadly Neutralizing Antibodies/*therapeutic use ; Clostridium Infections/diagnosis/epidemiology/prevention &amp; control/therapy ; Enterocolitis, Pseudomembranous/diagnosis/epidemiology/prevention &amp; control/*therapy ; *Fecal Microbiota Transplantation ; Fidaxomicin/therapeutic use ; Hand Hygiene ; Health Care Costs ; Humans ; Infection Control ; Kidney Failure, Chronic/epidemiology ; Length of Stay ; Metronidazole/therapeutic use ; Patient Isolation ; Renal Insufficiency, Chronic/*epidemiology ; Secondary Prevention ; Vancomycin/therapeutic use ; }, abstract = {Clostridioides difficile infection (CDI) is a major health-care burden and increasingly seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Increased antibiotic use, alteration in host defenses, and gastric acid suppression are some of the etiologies for increased risk of CDI in these populations. Patients with CKD/ESRD have a higher risk of initial episode, recurrence, and development of severe CDI than those without CKD or ESRD. Diagnosis and management of CDI in patients with CKD/ESRD are similar to that in the general population. The mortality, length of stay, and health-care costs are higher in patients with CDI and CKD/ESRD. Antimicrobial stewardship with reduction in antibiotic use along with infection-control measures such as contact isolation and hand hygiene with soap and water is essential in the control and prevention of CDI in patients with CKD/ESRD.}, }
@article {pmid30873549, year = {2019}, author = {Sood, A and Mahajan, R and Singh, A and Midha, V and Mehta, V and Narang, V and Singh, T and Singh Pannu, A}, title = {Role of Faecal Microbiota Transplantation for Maintenance of Remission in Patients With Ulcerative Colitis: A Pilot Study.}, journal = {Journal of Crohn's &amp; colitis}, volume = {13}, number = {10}, pages = {1311-1317}, doi = {10.1093/ecco-jcc/jjz060}, pmid = {30873549}, issn = {1876-4479}, mesh = {Adult ; Colitis, Ulcerative/pathology/prevention &amp; control/*therapy ; Colonoscopy ; *Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Pilot Projects ; Secondary Prevention/methods ; }, abstract = {OBJECTIVES: To study the role of faecal microbiota transplantation [FMT] in maintenance of remission in ulcerative colitis [UC].<br><br>METHODS: In this pilot study, patients with UC in clinical remission achieved after multi-session FMT were randomly allocated to either maintenance FMT or placebo colonoscopic infusion every 8 weeks, for 48 weeks. The standard of care [SOC] therapy was continued in all patients. The primary endpoint was maintenance of steroid-free clinical remission [Mayo score &#x2264;2, all subscores &#x2264;1] at Week 48. Secondary endpoints were achievement of endoscopic remission [endoscopic Mayo score 0] and histological remission [Nancy grade 0, 1] at Week 48.<br><br>RESULTS: In all, 61 patients in clinical remission were randomised to receive either FMT [n = 31] or placebo [n = 30]. The primary outcome was achieved in 27/31 [87.1%] patients allocated FMT versus 20/30 [66.7%] patients assigned placebo [p = 0.111]. Secondary endpoints of endoscopic remission (FMT: 18/31 [58.1%] versus placebo: 8/30 [26.7%], p = 0.026) and histological remission (FMT: 14/31 [45.2%] versus placebo: 5/30 [16.7%], p = 0. 033) were achieved in a significantly higher number of patients with FMT. Three patients receiving FMT [9.7%] and 8 patients on placebo [26.7%] relapsed. There were no serious adverse events necessitating discontinuation in patients on FMT; one patient who relapsed on placebo required colectomy.<br><br>CONCLUSIONS: Maintenance FMT in patients who are in clinical remission may help sustain clinical, endoscopic and histological remission in patients with UC.}, }
@article {pmid30867532, year = {2019}, author = {Xu, X and Fukui, H and Ran, Y and Tomita, T and Oshima, T and Watari, J and Miwa, H}, title = {Alteration of GLP-1/GPR43 expression and gastrointestinal motility in dysbiotic mice treated with vancomycin.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {4381}, pmid = {30867532}, issn = {2045-2322}, mesh = {Animals ; Body Weight/drug effects ; Dysbiosis/blood/chemically induced/metabolism ; Female ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Motility/*drug effects ; Gastrointestinal Tract/drug effects/metabolism/microbiology ; Glucagon-Like Peptide 1/*blood/metabolism ; Mice ; Receptors, G-Protein-Coupled/*metabolism ; Vancomycin/*pharmacology ; }, abstract = {Gut microbiota plays a pivotal role in various aspects of host physiology, including metabolism, gastrointestinal (GI) motility and hormonal secretion. In the present study, we investigated the effect of antibiotic-associated dysbiosis on metabolism and GI motility in relation to colonic expression of glucagon-like peptide-1 (GLP-1) and G protein coupled receptor (GPR)43. Specific pathogen-free (SPF) mice (ICR, 6 weeks old, female) were orally administered vancomycin (0.2 mg/ml) in drinking water for 7 days. In another experiment, germ-free (GF) mice (ICR, 6 weeks old, female) were subjected to oral fecal transplantation (FT) using a fecal bacterial suspension prepared from SPF mice that had received vancomycin treatment (FT-V) or one from untreated control SPF mice (FT-C). The gastrointestinal transit time (GITT) was measured by administration of carmine red (6% w/v) solution. The expression of GLP-1 and GPR43 was examined by immunohistochemistry and realtime RT-PCR, and the plasma GLP-1 level was measured by ELISA. In vancomycin-treated SPF mice, the diversity of the gut microbiota was significantly reduced and the abundance of Lactobacillus was markedly increased. Significant increases in body weight, cecum weight, plasma GLP-1 level and colonic GLP-1/GPR43 expression were also noted relative to the controls. These alterations were reproducible in GF mice with FT-V. Moreover, FT-V GF mice showed a significantly increased food intake and a significantly prolonged GITT in comparison with FT-C GF mice. Vancomycin-induced dysbiosis promotes body weight gain and prolongs GITT, accompanied by an increase of colonic GLP-1/GPR43 expression.}, }
@article {pmid30866714, year = {2019}, author = {Park, H and Laffin, MR and Jovel, J and Millan, B and Hyun, JE and Hotte, N and Kao, D and Madsen, KL}, title = {The success of fecal microbial transplantation in Clostridium difficile infection correlates with bacteriophage relative abundance in the donor: a retrospective cohort study.}, journal = {Gut microbes}, volume = {10}, number = {6}, pages = {676-687}, pmid = {30866714}, issn = {1949-0984}, support = {//CIHR/Canada ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteria/classification/genetics/isolation &amp; purification ; Bacteriophages/*classification/genetics ; Clostridioides difficile/physiology ; Clostridium Infections/microbiology/*therapy/*virology ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/microbiology/virology ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; *Tissue Donors ; Treatment Outcome ; }, abstract = {Background: Fecal microbial transplantation (FMT) is used in the treatment of relapsing Clostridium difficile infection (rCDI). Failure rate for FMT is as high as 10% but the mechanisms contributing to a failed FMT are not understood. We utilized metagenomic data to identify the role of bacteria and bacteriophages on FMT success.Results: Subjects with rCDI (n = 19) received FMT from volunteer donors (n = 7) via colonoscopy. Twelve patients fully recovered after a single FMT, while seven patients required a subsequent FMT. DNA was extracted from patient and donor stool samples for shotgun metagenomic analysis. Metagenomics libraries were analyzed focusing on bacterial taxonomy and bacteriophage sequences. Gammaproteobacteria were dominant in rCDI patients prior to FMT largely due to elevated levels of Klebsiella and Escherichia. A successful FMT led to increased levels of Clostridia and Bacteroidia and a reduction in Gammaproteobacteria. In contrast, a failed FMT led to no significant changes in bacterial composition. Bacteriophages were classified during whole metagenomic analysis of each sample and were markedly different between rCDI patients, donors, and a healthy control cohort (n = 96). Bacteriophage sequence reads were increased in CDI patients compared with donors and healthy controls. Successful FMT donors had higher bacteriophage α-diversity and lower relative abundance compared to the donors of a failed initial FMT.Conclusions: In this retrospective analysis, FMTs with increased bacteriophage α-diversity were more likely to successfully treat rCDI. In addition, the relative number of bacteriophage reads was lower in donations leading to a successful FMT. These results suggest that bacteriophage abundance may have some role in determining the relative success of FMT.}, }
@article {pmid30861553, year = {2019}, author = {Roggenbrod, S and Schuler, C and Haller, B and Sohn, M and Storr, M and Schepp, W and Gundling, F}, title = {[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {57}, number = {3}, pages = {296-303}, doi = {10.1055/a-0821-7166}, pmid = {30861553}, issn = {1439-7803}, mesh = {*Colitis, Ulcerative/psychology/therapy ; *Fecal Microbiota Transplantation/psychology ; Feces ; Female ; Humans ; Male ; *Patient Acceptance of Health Care ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) represents a treatment option for recurring Clostridium difficile-associated colitis. However, there is also evidence that FMT can be effective in treating ulcerative colitis. This study examined the approval and willingness of affected patients who underwent FMT.<br><br>METHODS: &#x2002;A standardized questionnaire containing 27 polar and open questions was dispatched to a cohort of 262 patients suffering from UC. It included questions regarding the FMT process, donors, and possible concerns. Additionally, aspects of social background and disease activity were addressed.<br><br>RESULTS: &#x2002;The response rate was 31.3&#x200a;% (n&#x200a;=&#x200a;82). Forty-eight (58.5&#x200a;%) patients were already aware of FMT. Forty-six (56.1&#x200a;%) were willing to undergo FMT if given a respective indication. The effectiveness of the procedure (40.2&#x200a;%), followed by failure of all other therapies (17.1&#x200a;%), formed the principal motivation. The transmission of possible infectious agents (26.8&#x200a;%), and the potential contamination of the stool graft leading to a deterioration of clinical symptoms, raised the most concerns. (20.7&#x200a;%).The preferred delivery system of FMT was capsules (67.1&#x200a;%), followed by colonoscopic application (47.6&#x200a;%). The patients were in favour of a donor proposed by the physician (52,4&#x200a;%). Willingness to undergo FMT did not differ significantly between genders (56.4&#x200a;% women vs. 57.1&#x200a;% men). Smokers (88.9&#x200a;%), patients who did not watch television at all (77.8&#x200a;%) and those with private health insurance, showed an increased willingness to undergo FMT.<br><br>CONCLUSION: &#x2002;For the majority of the UC patients surveyed, FMT represents a feasible treatment option. Approximately half of the respondents would consider FMT as an alternative treatment option, even inspite of a satisfactory disease response to current standard therapies. Unsurprisingly, there are concerns regarding the transmission of possible infectious agents and the hygienic implementation of FMT itself.}, }
@article {pmid30861317, year = {2019}, author = {Joseph, J and Saha, S and Greenberg-Worisek, AJ}, title = {Fecal Microbiota Transplantation: An Ambiguous Translational Pathway for a Promising Treatment.}, journal = {Clinical and translational science}, volume = {12}, number = {3}, pages = {206-208}, pmid = {30861317}, issn = {1752-8062}, support = {T32 GM065841/GM/NIGMS NIH HHS/United States ; }, mesh = {Clinical Trials as Topic ; Clostridioides difficile/physiology ; Clostridium Infections/microbiology ; *Fecal Microbiota Transplantation ; Humans ; Insurance, Health, Reimbursement ; *Translational Research, Biomedical ; }, }
@article {pmid30860879, year = {2019}, author = {Okamoto, T and Morino, K and Ugi, S and Nakagawa, F and Lemecha, M and Ida, S and Ohashi, N and Sato, D and Fujita, Y and Maegawa, H}, title = {Microbiome potentiates endurance exercise through intestinal acetate production.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {316}, number = {5}, pages = {E956-E966}, doi = {10.1152/ajpendo.00510.2018}, pmid = {30860879}, issn = {1522-1555}, mesh = {Acetates/*metabolism ; Animals ; Anti-Bacterial Agents/pharmacology ; Butyrates/metabolism ; Dietary Fiber/metabolism ; Fatty Acids, Volatile/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Mice ; *Physical Conditioning, Animal ; Physical Endurance/drug effects/*physiology ; Propionates/metabolism ; }, abstract = {The intestinal microbiome produces short-chain fatty acids (SCFAs) from dietary fiber and has specific effects on other organs. During endurance exercise, fatty acids, glucose, and amino acids are major energy substrates. However, little is known about the role of SCFAs during exercise. To investigate this, mice were administered either multiple antibiotics or a low microbiome-accessible carbohydrate (LMC) diet, before endurance testing on a treadmill. Two-week antibiotic treatment significantly reduced endurance capacity versus the untreated group. In the cecum acetate, propionate, and butyrate became almost undetectable in the antibiotic-treated group, plasma SCFA concentrations were lower, and the microbiome was disrupted. Similarly, 6-wk LMC treatment significantly reduced exercise capacity, and fecal and plasma SCFA concentrations. Continuous acetate but not saline infusion in antibiotic-treated mice restored their exercise capacity (P < 0.05), suggesting that plasma acetate may be an important energy substrate during endurance exercise. In addition, running time was significantly improved in LMC-fed mice by fecal microbiome transplantation from others fed a high microbiome-accessible carbohydrate diet and administered a single portion of fermentable fiber (P < 0.05). In conclusion, the microbiome can contribute to endurance exercise by producing SCFAs. Our findings provide new insight into the effects of the microbiome on systemic metabolism.}, }
@article {pmid30860274, year = {2019}, author = {Adamiak-Godlewska, A and Skorupska, K and Romanek-Piva, K and Pilat, J and Rechberger, T}, title = {Additional secure circular suture during sphincteroplasty - preliminary results on the efficacy of fecal incontinence surgery in urogynecological patients.}, journal = {Ginekologia polska}, volume = {90}, number = {2}, pages = {82-85}, doi = {10.5603/GP.2019.0014}, pmid = {30860274}, issn = {2543-6767}, mesh = {Adult ; Aged ; Anal Canal/*surgery ; Digestive System Surgical Procedures/*methods/*statistics &amp; numerical data ; Fecal Incontinence/*surgery ; Female ; Humans ; Middle Aged ; Pelvic Organ Prolapse/surgery ; Sutures ; Treatment Outcome ; Urinary Incontinence/surgery ; Urogenital Surgical Procedures/*statistics &amp; numerical data ; }, abstract = {OBJECTIVES: The paper is a ten case series study presenting women with complex pelvic floor disorders involving fecal incontinence (FI) with stress urinary incontinence or pelvic organ prolapse. Our study aimed at ascertaining whether FI-induced sphincteroplasty with an additional secure circular suture around the external anal sphincter muscle (EAS) may improve long term success rates.<br><br>MATERIALS AND METHODS: Twelve patients had scheduled urogynecological surgery and overlapping sphincteroplasty with the placement of an additional circular suture around the EAS. Of these, the status of ten women was established by way of the Cleveland Clinic Fecal Incontinence Score/Wexner Score before and about 70 months after surgery.<br><br>RESULTS: Statistical analysis of fecal incontinence score showed that patients were not completely cured from FI, but were significantly better (p = 0.011).<br><br>CONCLUSIONS: A circular secure suture around the external anal sphincter in FI patients may help to improve anal sphincter function.}, }
@article {pmid30859364, year = {2020}, author = {Wang, J and Wang, P and Li, D and Hu, X and Chen, F}, title = {Beneficial effects of ginger on prevention of obesity through modulation of gut microbiota in mice.}, journal = {European journal of nutrition}, volume = {59}, number = {2}, pages = {699-718}, pmid = {30859364}, issn = {1436-6215}, support = {D16110500540001//Beijing Municipal Science and Technology Project/ ; }, mesh = {Animals ; Diet ; Dietary Supplements/*statistics &amp; numerical data ; Disease Models, Animal ; Gastrointestinal Microbiome/*drug effects ; *Zingiber officinale ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/*prevention &amp; control ; }, abstract = {PURPOSE: Recent evidence has demonstrated that the gut microbiota plays a critical role in the treatment of obesity and other metabolic dysfunctions. Ginger (Zingiber officinale Roscoe), one of the most commonly used spices and dietary supplements, has been shown to exert beneficial effects against obesity and related disorders. However, to date, the mechanisms linking these effects to the gut microbiota remain unclear. This study aims to investigate the relationship between the gut microbiota and the metabolic adaptations resulting from ginger supplementation in mice.<br><br>METHODS: Four groups of mice were fed a normal chow diet (NCD) or a high-fat diet (HFD) with or without ginger supplementation for 16&#xa0;weeks. Lipid profiles, proinflammatory cytokines, glucose tolerance, microbiota composition and short-chain fatty acid (SCFA) concentrations were analyzed at the end of the experiment. In addition, microbiota-depleted mice were transplanted with the fecal microbiota of mice fed a HFD or mice fed a HFD along with ginger supplementation. Glucose tolerance and microbiota composition were assessed after a 8-week fecal microbiota transplantation (FMT).<br><br>RESULTS: We observed marked decreases in body weight, liver steatosis, and low-grade inflammation as well as amelioration of insulin resistance in the HFD-fed mice treated with ginger. Furthermore, ginger supplementation modulated the gut microbiota composition and increased species belonging to the Bifidobacterium genus and SCFA-producing bacteria (Alloprevotella and Allobaculum), along with increases in fecal SCFA concentrations. The FMT experiment showed anti-obesity and microbiota-modulating effects similar to those observed in the oral ginger-feeding experiment.<br><br>CONCLUSIONS: This study suggests that modulation of the gut microbiota as a result of ginger supplementation has a therapeutic effect on obesity in mice.}, }
@article {pmid30858872, year = {2019}, author = {Sartelli, M and Di Bella, S and McFarland, LV and Khanna, S and Furuya-Kanamori, L and Abuzeid, N and Abu-Zidan, FM and Ansaloni, L and Augustin, G and Bala, M and Ben-Ishay, O and Biffl, WL and Brecher, SM and Camacho-Ortiz, A and Caínzos, MA and Chan, S and Cherry-Bukowiec, JR and Clanton, J and Coccolini, F and Cocuz, ME and Coimbra, R and Cortese, F and Cui, Y and Czepiel, J and Demetrashvili, Z and Di Carlo, I and Di Saverio, S and Dumitru, IM and Eckmann, C and Eiland, EH and Forrester, JD and Fraga, GP and Frossard, JL and Fry, DE and Galeiras, R and Ghnnam, W and Gomes, CA and Griffiths, EA and Guirao, X and Ahmed, MH and Herzog, T and Kim, JI and Iqbal, T and Isik, A and Itani, KMF and Labricciosa, FM and Lee, YY and Juang, P and Karamarkovic, A and Kim, PK and Kluger, Y and Leppaniemi, A and Lohsiriwat, V and Machain, GM and Marwah, S and Mazuski, JE and Metan, G and Moore, EE and Moore, FA and Ordoñez, CA and Pagani, L and Petrosillo, N and Portela, F and Rasa, K and Rems, M and Sakakushev, BE and Segovia-Lohse, H and Sganga, G and Shelat, VG and Spigaglia, P and Tattevin, P and Tranà, C and Urbánek, L and Ulrych, J and Viale, P and Baiocchi, GL and Catena, F}, title = {2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients.}, journal = {World journal of emergency surgery : WJES}, volume = {14}, number = {}, pages = {8}, pmid = {30858872}, issn = {1749-7922}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/diagnosis/*therapy ; Enterocolitis, Pseudomembranous/etiology/prevention &amp; control ; Fecal Microbiota Transplantation/methods/trends ; Guidelines as Topic ; Humans ; Incidence ; Infection Control/methods/trends ; Postoperative Complications/*therapy ; Risk Factors ; }, abstract = {In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.}, }
@article {pmid30858572, year = {2019}, author = {Toubai, T and Fujiwara, H and Rossi, C and Riwes, M and Tamaki, H and Zajac, C and Liu, C and Mathew, AV and Byun, J and Oravecz-Wilson, K and Matsuda, I and Sun, Y and Peltier, D and Wu, J and Chen, J and Seregin, S and Henig, I and Kim, S and Brabbs, S and Pennathur, S and Chen, G and Reddy, P}, title = {Host NLRP6 exacerbates graft-versus-host disease independent of gut microbial composition.}, journal = {Nature microbiology}, volume = {4}, number = {5}, pages = {800-812}, pmid = {30858572}, issn = {2058-5276}, support = {K08 HL130944/HL/NHLBI NIH HHS/United States ; R01 CA203542/CA/NCI NIH HHS/United States ; R01 HL128046/HL/NHLBI NIH HHS/United States ; R01 AI075284/AI/NIAID NIH HHS/United States ; P01 CA039542/CA/NCI NIH HHS/United States ; R01 HL090775/HL/NHLBI NIH HHS/United States ; U2C DK110768/DK/NIDDK NIH HHS/United States ; K12 HD028820/HD/NICHD NIH HHS/United States ; P30 DK089503/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/*isolation &amp; purification ; Bone Marrow Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Graft vs Host Disease/immunology/*microbiology ; Humans ; Intestines/immunology/microbiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Cell Surface/genetics/*immunology ; Specific Pathogen-Free Organisms ; Transplantation, Homologous ; }, abstract = {Host NOD-like receptor family pyrin domain-containing 6 (NLRP6) regulates innate immune responses and gastrointestinal homeostasis. Its protective role in intestinal colitis and tumorigenesis is dependent on the host microbiome. Host innate immunity and microbial diversity also play a role in the severity of allogeneic immune-mediated gastrointestinal graft-versus-host disease (GVHD), the principal toxicity after allogeneic haematopoietic cell transplantation. Here, we examined the role of host NLRP6 in multiple murine models of allogeneic bone marrow transplantation. In contrast to its role in intestinal colitis, host NLRP6 aggravated gastrointestinal GVHD. The impact of host NLRP6 deficiency in mitigating GVHD was observed regardless of co-housing, antibiotic treatment or colonizing littermate germ-free wild-type and NLRP6-deficient hosts with faecal microbial transplantation from specific pathogen-free wild-type and Nlrp6[-/-] animals. Chimaera studies were performed to assess the role of NLRP6 expression on host haematopoietic and non-haematopoietic cells. The allogeneic [B6Ly5.2 → Nlrp6[-/-]] animals demonstrated significantly improved survival compared to the allogeneic [B6Ly5.2 → B6] animals, but did not alter the therapeutic graft-versus-tumour effects after haematopoietic cell transplantation. Our results unveil an unexpected, pathogenic role for host NLRP6 in gastrointestinal GVHD that is independent of variations in the intestinal microbiome and in contrast to its well-appreciated microbiome-dependent protective role in intestinal colitis and tumorigenesis.}, }
@article {pmid30852608, year = {2019}, author = {Azimirad, M and Yadegar, A and Asadzadeh Aghdaei, H and Kelly, CR}, title = {Enterotoxigenic Clostridium perfringens Infection as an Adverse Event After Faecal Microbiota Transplantation in Two Patients With Ulcerative Colitis and Recurrent Clostridium difficile Infection: A Neglected Agent in Donor Screening.}, journal = {Journal of Crohn's &amp; colitis}, volume = {13}, number = {7}, pages = {960-961}, doi = {10.1093/ecco-jcc/jjz006}, pmid = {30852608}, issn = {1876-4479}, mesh = {Adult ; *Clostridioides difficile ; Clostridium Infections/*etiology/microbiology ; *Clostridium perfringens ; Colitis, Ulcerative/complications/*therapy ; Donor Selection/*methods ; Fecal Microbiota Transplantation/*adverse effects ; Feces/*microbiology ; Humans ; Male ; Middle Aged ; Recurrence ; }, }
@article {pmid30852592, year = {2019}, author = {Hirten, RP and Grinspan, A and Fu, SC and Luo, Y and Suarez-Farinas, M and Rowland, J and Contijoch, EJ and Mogno, I and Yang, N and Luong, T and Labrias, PR and Peter, I and Cho, JH and Sands, BE and Colombel, JF and Faith, JJ and Clemente, JC}, title = {Microbial Engraftment and Efficacy of Fecal Microbiota Transplant for Clostridium Difficile in Patients With and Without Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {25}, number = {6}, pages = {969-979}, pmid = {30852592}, issn = {1536-4844}, support = {F31 DK112679/DK/NIDDK NIH HHS/United States ; R01 DK114038/DK/NIDDK NIH HHS/United States ; S10 OD018522/OD/NIH HHS/United States ; }, mesh = {Adult ; Bacteria/*classification ; Clostridioides difficile/*physiology ; Clostridium Infections/complications/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Inflammatory Bowel Diseases/*complications/microbiology ; Longitudinal Studies ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Recurrent and severe Clostridium difficile infections (CDI) are treated with fecal microbiota transplant (FMT). Uncertainty exists regarding FMT effectiveness for CDI with underlying inflammatory bowel disease (IBD) and regarding its effects on disease activity and effectiveness in transferring the donor microbiota to patients with and without IBD.<br><br>METHODS: Subjects with and without IBD who underwent FMT for recurrent or severe CDI between 2013 and 2016 at The Mount Sinai Hospital were followed for up to 6 months. The primary outcome was CDI recurrence 6 months after FMT. Secondary outcomes were (1) CDI recurrence 2 months after FMT; (2) frequency of IBD flare after FMT; (3) microbiota engraftment after FMT; (and 4) predictors of CDI recurrence.<br><br>RESULTS: One hundred thirty-four patients, 46 with IBD, were treated with FMT. Follow-up was available in 83 and 118 patients at 6 and 2 months, respectively. There was no difference in recurrence in patients with and without IBD at 6 months (38.7% vs 36.5%; P > 0.99) and 2 months (22.5% vs 17.9%; P = 0.63). Proton pump inhibitor use, severe CDI, and comorbid conditions were predictors of recurrence. Pre-FMT microbiota was not predictive of CDI recurrence. Subjects with active disease requiring medication escalation had reduced engraftment, with no difference in engraftment based on CDI recurrence or IBD endoscopic severity at FMT.<br><br>CONCLUSIONS: Inflammatory bowel disease did not affect CDI recurrence rates 6 months after FMT. Pre-FMT microbiota was not predictive of recurrence, and microbial engraftment was impacted in those requiring IBD treatment escalation, though not by CDI recurrence or IBD disease severity.}, }
@article {pmid30852460, year = {2019}, author = {Wang, H and Mei, L and Deng, Y and Liu, Y and Wei, X and Liu, M and Zhou, J and Ma, H and Zheng, P and Yuan, J and Li, M}, title = {Lactobacillus brevis DM9218 ameliorates fructose-induced hyperuricemia through inosine degradation and manipulation of intestinal dysbiosis.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {62}, number = {}, pages = {63-73}, doi = {10.1016/j.nut.2018.11.018}, pmid = {30852460}, issn = {1873-1244}, mesh = {Animals ; Diet/adverse effects/methods ; Disease Models, Animal ; Dysbiosis/*drug therapy/metabolism/urine ; Fructose/*administration &amp; dosage ; Gastrointestinal Microbiome/*drug effects ; Hyperuricemia/*drug therapy/etiology/urine ; Inosine/*metabolism/urine ; Intestines/drug effects/microbiology ; *Levilactobacillus brevis ; Male ; Mice ; Mice, Inbred BALB C ; Probiotics ; }, abstract = {OBJECTIVE: High fructose consumption exacerbates purine degradation and intestinal dysbiosis, which are closely related to the development of hyperuricemia. Probiotics are powerful weapons to combat metabolic disturbance and intestinal dysbiosis. Previously we isolated a Lactobacillus strain named DM9218 that could reduce the serum uric acid (UA) level by assimilating purine nucleosides. The present study aimed to evaluate the effects of DM9218 on high-fructose-induced hyperuricemia and to elucidate the underlying mechanisms.<br><br>METHODS: Mice were fed a normal diet, a high-fructose diet, or high-fructose diet with DM9218. Metabolic parameters, fructose- and UA-related metabolites, and fecal microbiota were investigated. Whole-genome sequencing of strain DM9218 was also conducted. In addition, an inosine hydrolase from DM9218 was heterologously expressed in Escherichia coli, and its inosine-degrading activity was detected.<br><br>RESULTS: Our results indicated that DM9218 could decrease serum UA level and hepatic xanthine oxidase activity in fructose-fed mice. It could protect against high-fructose-induced liver damage and retard UA accumulation by degrading inosine. The modulation effect of DM9218 on high-fructose-induced intestinal dysbiosis resulted in enhancement of intestinal barrier function and reduction of liver lipopolysaccharide, which was closely correlated with the down-regulation of inflammatory cytokine-stimulated xanthine oxidase expression and activity.<br><br>CONCLUSIONS: Lactobacillus brevis DM9218 is a probiotic strain with the potential to ameliorate fructose-induced hyperuricemia.}, }
@article {pmid30851429, year = {2019}, author = {Hibbard, J and Jiang, ZD and DuPont, HL}, title = {Fecal calprotectin and fecal indole predict outcome of fecal microbiota transplantation in subjects with recurrent Clostridium difficile infection.}, journal = {Anaerobe}, volume = {56}, number = {}, pages = {102-105}, doi = {10.1016/j.anaerobe.2019.03.006}, pmid = {30851429}, issn = {1095-8274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces/*chemistry ; Female ; Humans ; Indoles/*analysis ; Leukocyte L1 Antigen Complex/*analysis ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {Fecal calprotectin and indole were studied in 134 subjects with recurrent CDI before and after FMT. Reduced fecal calprotectin (p = 0.0353, 95% CI 0.1305-0.1439) and rising levels of indole (p < 0.0001, 95% CI < 0.0001-0.0003) predicted successful treatment. A ratio of recal calprotectin/indole may provide prognostic value for FMT (p = 0.0004, 95% CI 0.22-0.87).}, }
@article {pmid30850823, year = {2019}, author = {Cammarota, G and Ianiro, G}, title = {FMT for ulcerative colitis: closer to the turning point.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {16}, number = {5}, pages = {266-268}, doi = {10.1038/s41575-019-0131-0}, pmid = {30850823}, issn = {1759-5053}, mesh = {*Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; }, }
@article {pmid30848026, year = {2019}, author = {Chen, CC and Chen, YN and Liou, JM and Wu, MS and , }, title = {From germ theory to germ therapy.}, journal = {The Kaohsiung journal of medical sciences}, volume = {35}, number = {2}, pages = {73-82}, doi = {10.1002/kjm2.12011}, pmid = {30848026}, issn = {2410-8650}, support = {NTUH 106-P06//National Taiwan University Hospital/ ; NTUH 104-P05//National Taiwan University Hospital/ ; 107-0210-01-19-04//Translational Innovation of Biopharmaceutical Development-Technology Supporting Platform Axis/ ; MOHW107-TDU-B-211-123&#x2009;002//Ministry of Health and Welfare of Taiwan/ ; MOHW106-TDU-B-211-113&#x2009;002//Ministry of Health and Welfare of Taiwan/ ; MOST 107-3017-F-002-002//Ministry of Science and Technology, Executive Yuan, ROC, Taiwan/ ; TCTC-TR2 106-2321-B-002-025//Ministry of Science and Technology, Executive Yuan, ROC, Taiwan/ ; NTU-107 L9014-1//Ministry of Education (MOE) in Taiwan/ ; }, mesh = {Clinical Trials as Topic ; Disease ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects ; *Germ Theory of Disease ; Humans ; Probiotics/*pharmacology ; }, abstract = {Germ theory of disease and Koch's postulates has been governing our understanding of the role of microbes in human health since 19th century. The discovery of Helicobacter pylori (H. pylori) and H. pylori associated diseases has typically represented the concept and framework of Koch's postulates. Eradication of H. pylori to prevent peptic ulcers recurrence and gastric cancer is the triumph of this microbiology paradigm. Advances of next generation sequencing provide great insight into the unculturable microbes and show trillions of microbes have evolved with human beings. Research into the microbiome-the microbial communities (microbiota) and the host environment that they inhabit-has changed our understanding about microbes in human health and disease. The gut microbiota, the largest reservoir of the microbiome in human, plays a critical role in our catabolic-metabolism and immunity. This review will show the changes of the view of microbes on human health. We will briefly discuss dysbiosis, the disruption of symbiotic relationship between the host and microbiota, and the associated diseases. This leads to an idea to manipulate the microbiota, either by restoring missing functions or by eliminating harmful functions, to prevent or treat a variety of diseases. Current evidences of two common germ therapies, fecal microbiota transplantation and probiotics, in treating diseases will be reviewed.}, }
@article {pmid30847461, year = {2019}, author = {Olmedo, M and Reigadas, E and Valerio, M and Vázquez-Cuesta, S and Pajares, JA and Matilla, A and Muñoz, P and Bouza, E}, title = {Is it reasonable to perform Fecal Microbiota Transplantation for recurrent Clostridium difficile Infection in patients with liver cirrhosis?.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {32}, number = {2}, pages = {205-207}, pmid = {30847461}, issn = {1988-9518}, mesh = {Aged ; Aged, 80 and over ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*complications/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Liver Cirrhosis/*complications ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; }, }
@article {pmid30845942, year = {2019}, author = {Biagi, E and Zama, D and Rampelli, S and Turroni, S and Brigidi, P and Consolandi, C and Severgnini, M and Picotti, E and Gasperini, P and Merli, P and Decembrino, N and Zecca, M and Cesaro, S and Faraci, M and Prete, A and Locatelli, F and Pession, A and Candela, M and Masetti, R}, title = {Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders.}, journal = {BMC medical genomics}, volume = {12}, number = {1}, pages = {49}, pmid = {30845942}, issn = {1755-8794}, mesh = {Acute Disease ; Adult ; Biodiversity ; Female ; *Gastrointestinal Microbiome ; Graft vs Host Disease/etiology/*microbiology ; Hematologic Diseases/immunology/microbiology/*therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Male ; Time Factors ; Transplantation, Homologous/adverse effects ; }, abstract = {BACKGROUND: The onset of acute Graft-versus-Host Disease (aGvHD) has been correlated with the gut microbiota (GM) composition, but experimental observations are still few, mainly involving cohorts of adult patients. In the current scenario where fecal microbiota transplantation has been used as a pioneer therapeutic approach to treat steroid-refractory aGvHD, there is an urgent need to expand existing observational studies of the GM dynamics in Hematopoietic Stem Cell Transplantation (HSCT). Aim of the present study is to explore the GM trajectory in 36 pediatric HSCT recipients in relation to aGvHD onset.<br><br>METHODS: Thirty-six pediatric patients, from four transplantation centers, undergoing HSCT were enrolled in the study. Stools were collected at three time points: before HSCT, at time of engraftment and&#x2009;>&#x2009;30&#x2009;days following HSCT. Changes in the GM phylogenetic structure were studied by 16S rRNA gene Illumina sequencing and phylogenetic assignation.<br><br>RESULTS: Children developing gut aGvHD had a dysbiotic GM layout before HSCT occurred. This putative aGvHD-predisposing ecosystem state was characterized by (i) reduced diversity, (ii) lower Blautia content, (iii) increase in Fusobacterium abundance. At time of engraftment, the GM structure underwent a deep rearrangement in all patients but, regardless of the occurrence of aGvHD and its treatment, it reacquired a eubiotic configuration from day 30.<br><br>CONCLUSIONS: We found a specific GM signature before HSCT predictive of subsequent gut aGvHD occurrence. Our data may open the way to a GM-based stratification of the risk of developing aGvHD in children undergoing HSCT, potentially useful also to identify patients benefiting from prophylactic fecal transplantation.}, }
@article {pmid30844549, year = {2019}, author = {Meng, X and Zhou, HY and Shen, HH and Lufumpa, E and Li, XM and Guo, B and Li, BZ}, title = {Microbe-metabolite-host axis, two-way action in the pathogenesis and treatment of human autoimmunity.}, journal = {Autoimmunity reviews}, volume = {18}, number = {5}, pages = {455-475}, doi = {10.1016/j.autrev.2019.03.006}, pmid = {30844549}, issn = {1873-0183}, mesh = {Autoimmune Diseases/immunology/*metabolism/*microbiology/*therapy ; Autoimmunity/physiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/immunology/physiology ; Host Microbial Interactions/*physiology ; Humans ; Metabolic Networks and Pathways/immunology ; Prebiotics/microbiology ; Probiotics/metabolism/therapeutic use ; }, abstract = {The role of microorganism in human diseases cannot be ignored. These microorganisms have evolved together with humans and worked together with body's mechanism to maintain immune and metabolic function. Emerging evidence shows that gut microbe and their metabolites open up new doors for the study of human response mechanism. The complexity and interdependence of these microbe-metabolite-host interactions are rapidly being elucidated. There are various changes of microbial levels in models or in patients of various autoimmune diseases (AIDs). In addition, the relevant metabolites involved in mechanism mainly include short-chain fatty acids (SCFAs), bile acids (BAs), and polysaccharide A (PSA). Meanwhile, the interaction between microbes and host genes is also a factor that must be considered. It has been demonstrated that human microbes are involved in the development of a variety of AIDs, including organ-specific AIDs and systemic AIDs. At the same time, microbes or related products can be used to remodel body's response to alleviate or cure diseases. This review summarizes the latest research of microbes and their related metabolites in AIDs. More importantly, it highlights novel and potential therapeutics, including fecal microbial transplantation, probiotics, prebiotics, and synbiotics. Nonetheless, exact mechanisms still remain elusive, and future research will focus on finding a specific strain that can act as a biomarker of an autoimmune disease.}, }
@article {pmid30844145, year = {2019}, author = {Chang, CS and Ruan, JW and Kao, CY}, title = {An overview of microbiome based strategies on anti-obesity.}, journal = {The Kaohsiung journal of medical sciences}, volume = {35}, number = {1}, pages = {7-16}, doi = {10.1002/kjm2.12010}, pmid = {30844145}, issn = {2410-8650}, support = {106-2628-B-400-001-MY3//Ministry of Science and Technology, Taiwan (MOST)/ ; 104-2320-B-400-019-MY3//Ministry of Science and Technology, Taiwan (MOST)/ ; IM-107-PP-04//National Health Research Institutes (NHRI)/ ; }, mesh = {Animals ; Anti-Obesity Agents/therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Obesity/genetics/*microbiology/therapy ; Probiotics/therapeutic use ; }, abstract = {With the significant global obesity epidemic and emerging strong scientific evidence that connected gut microbiota to obesity, intervening obesity by targeting gut microbiota has become a trendy strategy. Particularly the application of probiotics has become remarkably popular because of their expected association with gut microbiota modulation. Although there are many literatures on the effects of probiotics in obese animal models, most of them reported the effects of probiotic bacteria on metabolic indications with limited information on anti-obesity itself. Besides, some probiotics have been shown to reduce certain metabolic symptoms but they failed to achieve weight loss. This report reviewed the current literatures on the anti-obesity effects of next-generation probiotics in various animal obesity models and discussed the beneficial potential of fecal microbiota transplantation in treating obesity in humans. The purpose of this article is to help guide further research improve the probiotic bacteria experiments in more precise animal obesity models by standardizing the anti-obesogenesis, obesity control, and treatment assays and hopefully the evidence-based investigations on harnessing gut microbiota through next-generation probiotics or fecal microbiota transplantation will develop new interventions to promote and achieve anti-obesity.}, }
@article {pmid30841760, year = {2019}, author = {Cammarota, G and Gallo, A and Ianiro, G and Montalto, M}, title = {Emerging drugs for the treatment of clostridium difficile.}, journal = {Expert opinion on emerging drugs}, volume = {24}, number = {1}, pages = {17-28}, doi = {10.1080/14728214.2019.1591371}, pmid = {30841760}, issn = {1744-7623}, mesh = {Anti-Bacterial Agents/*administration &amp; dosage ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*drug therapy/epidemiology/microbiology ; Cross Infection/*drug therapy/epidemiology/microbiology ; Drug Development/methods ; Fecal Microbiota Transplantation/methods ; Humans ; Practice Guidelines as Topic ; }, abstract = {Clostridium difficile or Clostridioides difficile (C. difficile) infection represents the most common cause of healthcare-associated infection. Over the last decades, the incidence and severity of C. difficile infection is rapidly increasing, with a significant impact on morbidity and mortality, and burden on health care system. Orally administered vancomycin and fidaxomicin are the therapeutic options of choice for initial C. difficile infection and fecal microbiota transplant for the recurrence infection. Furthermore, in recent years several new antibiotics with narrow-spectrum activity and low intestinal resorption have been developed, including surotomycin, cadazolid, and ridinilazol, and novel toxoid vaccines are expected to be efficacious in the prevention of C. difficile infection. Areas covered: Literature review was performed to select publications about current guidelines and phase-II/III trials on emerging drugs. These include novel antibiotics, monoclonal antibodies, vaccines, and fecal microbiota transplantation. Expert opinion: We have today a wide spectrum of promising therapeutic possibilities against infection. Pivotal future clinical trials may be crucial in developing effective strategies to optimize outcomes, mainly in high-risk population.}, }
@article {pmid30840892, year = {2019}, author = {Rangan, P and Choi, I and Wei, M and Navarrete, G and Guen, E and Brandhorst, S and Enyati, N and Pasia, G and Maesincee, D and Ocon, V and Abdulridha, M and Longo, VD}, title = {Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology.}, journal = {Cell reports}, volume = {26}, number = {10}, pages = {2704-2719.e6}, pmid = {30840892}, issn = {2211-1247}, support = {P01 AG034906/AG/NIA NIH HHS/United States ; P01 AG055369/AG/NIA NIH HHS/United States ; R01 AG020642/AG/NIA NIH HHS/United States ; R01 AG025135/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Fasting/*physiology ; Humans ; Inflammatory Bowel Diseases/pathology/*therapy ; Intestines/pathology ; Mice ; Microbiota/*drug effects ; Regeneration ; }, abstract = {Dietary interventions are potentially effective therapies for inflammatory bowel diseases (IBDs). We tested the effect of 4-day fasting-mimicking diet (FMD) cycles on a chronic dextran sodium sulfate (DSS)-induced murine model resulting in symptoms and pathology associated with IBD. These FMD cycles reduced intestinal inflammation, increased stem cell number, stimulated protective gut microbiota, and reversed intestinal pathology caused by DSS, whereas water-only fasting increased regenerative and reduced inflammatory markers without reversing pathology. Transplants of Lactobacillus or fecal microbiota from DSS- and FMD-treated mice reversed DSS-induced colon shortening, reduced inflammation, and increased colonic stem cells. In a clinical trial, three FMD cycles reduced markers associated with systemic inflammation. The effect of FMD cycles on microbiota composition, immune cell profile, intestinal stem cell levels and the reversal of pathology associated with IBD in mice, and the anti-inflammatory effects demonstrated in a clinical trial show promise for FMD cycles to ameliorate IBD-associated inflammation in humans.}, }
@article {pmid30840761, year = {2019}, author = {Goyal, A and Morowitz, M}, title = {Author's Reply to Drs. Franco Scaldaferri and Valentina Petito, PhD.}, journal = {Inflammatory bowel diseases}, volume = {25}, number = {8}, pages = {e102}, doi = {10.1093/ibd/izz029}, pmid = {30840761}, issn = {1536-4844}, mesh = {Child ; Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases ; *Microbiota ; }, }
@article {pmid30840758, year = {2019}, author = {Petito, V and Fiore, L and Lopetuso, LR and Scaldaferri, F}, title = {Commentary to "Safety, Clinical Response, and Microbiome Findings Following Fecal Microbiota Transplant in Children With Inflammatory Bowel Disease".}, journal = {Inflammatory bowel diseases}, volume = {25}, number = {8}, pages = {e101}, doi = {10.1093/ibd/izz031}, pmid = {30840758}, issn = {1536-4844}, mesh = {Child ; Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases ; *Microbiota ; }, }
@article {pmid30837698, year = {2019}, author = {Thoma, C}, title = {Bile salt hydrolases involved in the effectiveness of FMT for Clostridium difficile infection.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {16}, number = {4}, pages = {198}, doi = {10.1038/s41575-019-0128-8}, pmid = {30837698}, issn = {1759-5053}, mesh = {Amidohydrolases ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid30836147, year = {2019}, author = {Viennois, E and Gewirtz, AT and Chassaing, B}, title = {Chronic Inflammatory Diseases: Are We Ready for Microbiota-based Dietary Intervention?.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {8}, number = {1}, pages = {61-71}, pmid = {30836147}, issn = {2352-345X}, support = {R01 DK083890/DK/NIDDK NIH HHS/United States ; R01 DK099071/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Dysbiosis/*diet therapy ; Emulsifying Agents/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Humans ; Inflammation/*diet therapy/microbiology ; }, abstract = {The last 15 years have witnessed the emergence of a new field of research that focuses on the roles played by the intestinal microbiota in health and disease. This research field has produced accumulating evidence indicating that dysregulation of host-microbiota interactions contributes to a range of chronic inflammatory diseases, including inflammatory bowel diseases, colorectal cancer, and metabolic syndrome. Although dysregulation of the microbiota can take complex forms, in some cases, specific bacterial species that can drive specific clinical outcomes have been identified. Among the numerous factors influencing the intestinal microbiota composition, diet is a central actor, wherein numerous dietary factors can beneficially or detrimentally impact the host/microbiota relationship. This review will highlight recent literature that has advanced understanding of microbiota-diet-disease interplay, with a central focus on the following question: Are we ready to use intestinal microbiota composition-based personalized dietary interventions to treat chronic inflammatory diseases?}, }
@article {pmid30835680, year = {2019}, author = {Wallace, DJ and Sayre, NL and Patterson, TT and Nicholson, SE and Hilton, D and Grandhi, R}, title = {Spinal cord injury and the human microbiome: beyond the brain-gut axis.}, journal = {Neurosurgical focus}, volume = {46}, number = {3}, pages = {E11}, doi = {10.3171/2018.12.FOCUS18206}, pmid = {30835680}, issn = {1092-0684}, support = {IK2 BX003240/BX/BLRD VA/United States ; }, mesh = {Animals ; Bacterial Translocation ; Brain Injuries, Traumatic/microbiology ; Burns/microbiology ; Dysbiosis/complications/immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Feedback, Physiological ; *Gastrointestinal Microbiome ; Humans ; Immunity, Mucosal/immunology ; Intestinal Mucosa/immunology/microbiology ; Mice ; Probiotics/therapeutic use ; Rats ; Sepsis/etiology/microbiology ; Species Specificity ; Spinal Cord Injuries/complications/immunology/*microbiology ; Stroke/microbiology/therapy ; }, abstract = {In addition to standard management for the treatment of the acute phase of spinal cord injury (SCI), implementation of novel neuroprotective interventions offers the potential for significant reductions in morbidity and long-term health costs. A better understanding of the systemic changes after SCI could provide insight into mechanisms that lead to secondary injury. An emerging area of research involves the complex interplay of the gut microbiome and the CNS, i.e., a brain-gut axis, or perhaps more appropriately, a CNS-gut axis. This review summarizes the relevant literature relating to the gut microbiome and SCI. Experimental models in stroke and traumatic brain injury demonstrate the bidirectional communication of the CNS to the gut with postinjury dysbiosis, gastrointestinal-associated lymphoid tissue-mediated neuroinflammatory responses, and bacterial-metabolite neurotransmission. Similar findings are being elucidated in SCI as well. Experimental interventions in these areas have shown promise in improving functional outcomes in animal models. This commensal relationship between the human body and its microbiome, particularly the gut microbiome, represents an exciting frontier in experimental medicine.}, }
@article {pmid30834680, year = {2019}, author = {Lin, P}, title = {Importance of the intestinal microbiota in ocular inflammatory diseases: A review.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {47}, number = {3}, pages = {418-422}, doi = {10.1111/ceo.13493}, pmid = {30834680}, issn = {1442-9071}, support = {P30 EY010572/EY/NEI NIH HHS/United States ; K08 EY022948/EY/NEI NIH HHS/United States ; }, mesh = {Gastrointestinal Microbiome/*physiology ; Humans ; Microbiota/*physiology ; Uveitis/*physiopathology ; }, abstract = {The purpose of this article is to review the literature on relationships between the intestinal microbiota and ocular inflammatory disease, specifically non-infectious uveitis and age-related macular degeneration. The importance of the intestinal microbiota in uveitis pathogenesis has been shown by multiple groups demonstrating that alterations in the microbiota induced by certain oral antibiotics results in reduced uveitis severity, and another group demonstrating that a commensal intestinal bacterial antigen activates retina-specific autoreactive T cells, potentially indicating a commensal trigger for uveitis. Additionally, commensal intestinal bacterial metabolite short chain fatty acids can be utilized to suppress autoimmune uveitis. Age-related macular degeneration is associated with intestinal dysbiosis, which is partially influenced by genetic risk alleles and AREDS supplementation. Strategies for therapeutically targeting the intestinal microbiota might involve several approaches, including the use of antibiotics, dietary changes, drugs that supplement beneficial bacterial metabolites or target causative bacterial strains, dietary strategies or faecal microbial transplantation. In summary, the intestinal microbiota are at the cross-roads of genetic and environmental factors that can promote ocular conditions such as non-infectious uveitis and age-related macular degeneration, partially via its dynamic influence on mucosal and systemic immunity. The intestinal microbiome thus represents a salient potential target for therapeutic modulation to treat these potentially blinding conditions.}, }
@article {pmid30834334, year = {2019}, author = {Kim, P and Gadani, A and Abdul-Baki, H and Mitre, R and Mitre, M}, title = {Fecal microbiota transplantation in recurrent Clostridium difficile infection: A retrospective single-center chart review.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {3}, number = {1}, pages = {4-9}, pmid = {30834334}, issn = {2397-9070}, abstract = {BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) has been proposed as a treatment option for patients with recurrent Clostridium difficile (C. difficile) infection but remains a novel option. We examined if FMT is an effective means of treating recurrent C. difficile infection.<br><br>METHODS: A retrospective review of 35 patients who underwent FMT was completed. Demographics and other variables, including the use of proton pump inhibitor therapy and history of inflammatory bowel disease, were collected.<br><br>RESULTS: Twenty-five patients (71.4%) belonged to a high-risk population (working in a hospital setting, rehabilitation center, or nursing facility) and a total of 74.3% of patients (n =&#x2009;26 patients) had no history of proton pump inhibitor use. Twenty-five patients (71.4%) had used metronidazole prior to transplantation, 35 patients (100%) had used vancomycin, and 7 patients (20%) had used fidaxomicin for prior infection. Four patients (11.4%) had used all three antibiotics during prior treatment. Of the eight patients who had a history of inflammatory bowel disease, six (75%) experienced resolution of symptoms after transplantation. A total of 30 patients (85.7%) had resolution of their symptoms 6-8 weeks' posttransplant, while 5 patients (14.3%) continued to have symptoms.<br><br>CONCLUSIONS: Our retrospective chart review supports that patients benefit from FMT in the setting of recurrent C. difficile infection.}, }
@article {pmid30833676, year = {2020}, author = {Pearson-Leary, J and Zhao, C and Bittinger, K and Eacret, D and Luz, S and Vigderman, AS and Dayanim, G and Bhatnagar, S}, title = {The gut microbiome regulates the increases in depressive-type behaviors and in inflammatory processes in the ventral hippocampus of stress vulnerable rats.}, journal = {Molecular psychiatry}, volume = {25}, number = {5}, pages = {1068-1079}, pmid = {30833676}, issn = {1476-5578}, mesh = {Animals ; Anxiety ; Behavior, Animal ; Depression ; *Gastrointestinal Microbiome ; Hippocampus ; Rats ; Stress, Psychological ; }, abstract = {Chronic exposure to stress is associated with increased incidence of depression, generalized anxiety, and PTSD. However, stress induces vulnerability to such disorders only in a sub-population of individuals, as others remain resilient. Inflammation has emerged as a putative mechanism for promoting stress vulnerability. Using a rodent model of social defeat, we have previously shown that rats with short-defeat latencies (SL/vulnerable rats) show increased anxiety- and depression-like behaviors, and these behaviors are mediated by inflammation in the ventral hippocampus. The other half of socially defeated rats show long-latencies to defeat (LL/resilient) and are similar to controls. Because gut microbiota are important activators of inflammatory substances, we assessed the role of the gut microbiome in mediating vulnerability to repeated social defeat stress. We analyzed the fecal microbiome of control, SL/vulnerable, and LL/resilient rats using shotgun metagenome sequencing and observed increased expression of immune-modulating microbiota, such as Clostridia, in SL/vulnerable rats. We then tested the importance of gut microbiota to the SL/vulnerable phenotype. In otherwise naive rats treated with microbiota from SL/vulnerable rats, there was higher microglial density and IL-1β expression in the vHPC, and higher depression-like behaviors relative to rats that received microbiota from LL/resilient rats, non-stressed control rats, or vehicle-treated rats. However, anxiety-like behavior during social interaction was not altered by transplant of the microbiome of SL/vulnerable rats into non-stressed rats. Taken together, the results suggest the gut microbiome contributes to the depression-like behavior and inflammatory processes in the vHPC of stress vulnerable individuals.}, }
@article {pmid30832423, year = {2019}, author = {Álvarez-Mercado, AI and Navarro-Oliveros, M and Robles-Sánchez, C and Plaza-Díaz, J and Sáez-Lara, MJ and Muñoz-Quezada, S and Fontana, L and Abadía-Molina, F}, title = {Microbial Population Changes and Their Relationship with Human Health and Disease.}, journal = {Microorganisms}, volume = {7}, number = {3}, pages = {}, pmid = {30832423}, issn = {2076-2607}, support = {PI-0538-2017//Junta de Andaluc&#xed;a/ ; }, abstract = {Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty liver disease and type 2 diabetes. Thus, maintaining a healthy gut ecosystem could aid in avoiding the early onset and development of these diseases. Furthermore, it is mandatory to evaluate the alterations in the microbiota associated with pathophysiological conditions and how to counteract them to restore intestinal homeostasis. This review highlights and critically discusses recent literature focused on identifying changes in and developing gut microbiota-targeted interventions (probiotics, prebiotics, diet, and fecal microbiota transplantation, among others) for the above-mentioned pathologies. We also discuss future directions and promising approaches to counteract unhealthy alterations in the gut microbiota. Altogether, we conclude that research in this field is currently in its infancy, which may be due to the large number of factors that can elicit such alterations, the variety of related pathologies, and the heterogeneity of the population involved. Further research on the effects of probiotics, prebiotics, or fecal transplantations on the composition of the human gut microbiome is necessary.}, }
@article {pmid30828114, year = {2018}, author = {Pathirana, WGW and Chubb, SP and Gillett, MJ and Vasikaran, SD}, title = {Faecal Calprotectin.}, journal = {The Clinical biochemist. Reviews}, volume = {39}, number = {3}, pages = {77-90}, pmid = {30828114}, issn = {0159-8090}, abstract = {Calprotectin is a calcium- and zinc-binding protein of the S-100 protein family which is mainly found within neutrophils and throughout the human body. The presence of calprotectin in faeces is a consequence of neutrophil migration into the gastrointestinal tissue due to an inflammatory process. Faecal calprotectin concentrations demonstrate good correlation with intestinal inflammation and faecal calprotectin is used as a biomarker in gastrointestinal disorders. Faecal calprotectin is a very sensitive marker for inflammation in the gastrointestinal tract, and useful for the differentiation of inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). Faecal calprotectin is used for the diagnosis, monitoring disease activity, treatment guidance and prediction of disease relapse and post-operative recurrence in IBD. There may also potentially be a role for faecal calprotectin in the management of infectious gastroenteritis, acute appendicitis, peptic ulcer disease, cystic fibrosis, coeliac disease, transplant rejection and graft versus host disease. Further studies are needed to confirm its utility in these conditions. Analysis of faecal calprotectin consists of an extraction step followed by quantification by immunoassay. Over the past few decades, several assays and extraction devices including point-of-care methods have been introduced by manufacturers. The manufacturer-quoted cut-off values for different faecal calprotectin assays are generally similar. However, the sensitivities and specificities at a given cut-off, and therefore the optimum cut-off values, are different between assays. A reference standard for calprotectin is lacking. Therefore, assay standardisation is required for more accurate and traceable test results for faecal calprotectin.}, }
@article {pmid30827274, year = {2019}, author = {Albarrak, AA and Romana, BS and Uraz, S and Yousef, MH and Juboori, AA and Tahan, V}, title = {Clostridium Difficile Infection in Inflammatory Bowel Disease Patients.}, journal = {Endocrine, metabolic &amp; immune disorders drug targets}, volume = {19}, number = {7}, pages = {929-935}, doi = {10.2174/1871530319666190301120558}, pmid = {30827274}, issn = {2212-3873}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Biological Therapy/methods ; Clostridium Infections/*epidemiology/physiopathology/*therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Agents/pharmacology/therapeutic use ; Gastrointestinal Microbiome/drug effects/physiology ; Humans ; Inflammatory Bowel Diseases/*epidemiology/physiopathology/*therapy ; }, abstract = {BACKGROUND: The rising incidence of Clostridium difficile infection (CDI) in the general population has been recognized by health care organizations worldwide. The emergence of hypervirulent strains has made CDI more challenging to understand and treat. Inflammatory bowel disease (IBD) patients are at higher risk of infection, including CDI.<br><br>OBJECTIVE: A diagnostic approach for recurrent CDI has yet to be validated, particularly for IBD patients. Enzyme immunoassay (EIA) for toxins A and B, as well as glutamate dehydrogenase EIA, are both rapid testing options for the identification of CDI. Without a high index of suspicion, it is challenging to initially differentiate CDI from an IBD flare based on clinical evaluation alone.<br><br>METHODS: Here, we provide an up-to-date review on CDI in IBD patients. When caring for an IBD patient with suspected CDI, it is appropriate to empirically treat the presumed infection while awaiting further test results.<br><br>RESULTS: Treatment with vancomycin or fidaxomicin, but not oral metronidazole, has been advocated by an expert review from the clinical practice update committee of the American Gastroenterology Association. Recurrent CDI is more common in IBD patients compared to non-IBD patients (32% versus 24%), thus more aggressive treatment is recommended for IBD patients along with early consideration of fecal microbiota transplant.<br><br>CONCLUSION: Although the use of infliximab during CDI has been debated, clinical experience exists supporting its use in an IBD flare, even with active CDI when needed.}, }
@article {pmid30825120, year = {2020}, author = {Schwandner, F and Klimars, U and Gock, M and Schiffmann, L and Witte, M and Schiergens, T and Rentsch, M and Klar, E and Kühn, F}, title = {The Water-Holding Procedure for Ensuring Postoperative Continence Prior Restoring Intestinal Continuity.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {24}, number = {2}, pages = {411-417}, pmid = {30825120}, issn = {1873-4626}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anal Canal/*physiopathology/surgery ; Defecation ; *Enterostomy ; Fecal Incontinence/*physiopathology ; Female ; Gastrointestinal Diseases/surgery ; Humans ; Male ; Manometry ; Middle Aged ; Pilot Projects ; Postoperative Period ; Predictive Value of Tests ; Prospective Studies ; Water ; }, abstract = {BACKGROUND: A defunctioning stoma can become necessary in a relevant number of patients undergoing gastrointestinal surgery. As a matter of course, patients seek an early closure of the stoma. However, preoperative management of these patients varies and the prediction of continence after stoma removal can become challenging. Patients might be fully continent despite low manometric pressures and vice versa. An easy and reliable way to predict continence after stoma reversal would improve patients' management and outcome. Although frequently performed in various surgical centers in Germany, there is no published data on the water-holding test. Hence, this is the first study evaluating the role of the test in clinical practice.<br><br>METHOD: We performed a prospective pilot study to evaluate the role of anorectal manometry and the water-holding procedure as a predictor of postoperative continence prior to stoma reversal. Inclusion criteria were a successfully passed water-holding test, any type of fecal diversion and the possibility of restoring intestinal continuity. Preoperative low manometric pressure levels were not an exclusion criteria for stoma reversal. Fifty-two patients with ostomy were consecutively enrolled in this study between October 2013 and February 2016. Anorectal manometry was performed in all patients prior to stoma reversal. After stoma removal, patients were followed-up for 6&#xa0;months. Postoperative incontinence was determined using the Wexner incontinence score.<br><br>RESULTS: A total of 52 patients (38 males, 14 females) were included at an average age of 59 (range 33-83) years. Most frequent indications for intestinal diversion were rectal cancer surgery, IBD-related surgery, or surgery for diverticular disease. Low anterior rectal resection was performed in 17 patients (32.7%), followed by a proctocolectomy in 9 (17.3%), colectomy in 9 (17.3%), and recto-sigmoid resection in 7 patients (13.5%). Median time from stoma creation to reversal was 206&#xa0;days (range 48-871&#xa0;days). All patients had successfully passed the standardized water-holding test. At the same time, the majority of patients had low preoperative manometric pressure values and would normally not have been reversed at that point. The median postoperative Wexner incontinence score was at 1.5 (range 0-20), 0.5 (range 0-14), and 0 (range 0-11) at 14, 60, and 180&#xa0;days after stoma reversal. Low preoperative manometric squeeze and/or resting pressure levels were not associated with a higher postoperative incontinence score at 14, 60, or 180&#xa0;days after stoma reversal.<br><br>CONCLUSION: A standardized water-holding test can function as an easy and reliable method before stoma reversal to predict sufficient postoperative fecal continence. In case of a sufficient water-holding test despite low manometric pressure levels, the risk for postoperative anal incontinence seems to be low. Preoperative manometric pressure levels do not appear to predict postoperative continence.}, }
@article {pmid30821676, year = {2019}, author = {Grace, E and Chahine, EB}, title = {Updates on Clostridioides (Clostridium) difficile Infection With Emphasis on Long-Term Care.}, journal = {The Senior care pharmacist}, volume = {34}, number = {1}, pages = {29-42}, doi = {10.4140/TCP.n.2019.29}, pmid = {30821676}, issn = {2639-9636}, abstract = {OBJECTIVE: To provide a review of the classification, epidemiology, risk factors, diagnosis, treatment, and prevention of Clostridioides (Clostridium) difficile (C. difficile) infection (CDI) with an emphasis on longterm care.<br><br>DATA SOURCES: PubMed and Google Scholar were searched for relevant literature using a combination of the following terms: C. difficile, classification, epidemilogy, risk factors, diagnosis, treatment, prevention, and long-term care. Sources were limited to human data.<br><br>The main article reviewed was the 2017 CDI guidelines of the Infectious Diseases Society of American and the Society for Healthcare Epidemiology of America. Other articles were reviewed for relevance to CDI in long-term care settings.<br><br>DATA SYNTHESIS: CDI is associated with significant morbidity and mortality, particularly in older adults. The primary risk factors are advanced age and receipt of antibiotics. Diagnosis is suspected based on signs and symptoms and confirmed by laboratory tests. Vancomycin and fidaxomicin have replaced metronidazole as the drugs of choice for CDI. Fidaxomicin is associated with a lower risk of recurrence than vancomycin. Fecal microbiota transplantation is reserved for patients with multiple recurrences. Bezlotoxumab can be used in addition to standard therapy to prevent CDIs in patients at high risk for recurrence. Infection control strategies and antibiotic stewardship programs are known to reduce the rates of CDIs in institutional settings.<br><br>CONCLUSION: CDI is largely iatrogenic, and diagnosis is based on clinical presentation and laboratory tests. Treatment options include vancomycin, fidaxomicin, and fecal microbiota transplantation. Prevention centers around infection control and antibiotic stewardship. More research is needed in long-term care settings.}, }
@article {pmid30820491, year = {2019}, author = {Lam, TJ and Ye, Y}, title = {CRISPRs for Strain Tracking and Their Application to Microbiota Transplantation Data Analysis.}, journal = {The CRISPR journal}, volume = {2}, number = {1}, pages = {41-50}, pmid = {30820491}, issn = {2573-1599}, support = {R01 AI108888/AI/NIAID NIH HHS/United States ; R01 AI143254/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Typing Techniques/*methods ; CRISPR-Cas Systems ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Computational Biology/methods ; DNA, Intergenic/classification/*genetics/metabolism ; Datasets as Topic ; Dysbiosis/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Humans ; Metagenome ; }, abstract = {CRISPR-Cas systems are adaptive immune systems naturally found in bacteria and archaea. Prokaryotes use these immune systems to defend against invaders, which include phages, plasmids, and other mobile genetic elements. Relying on the integration of spacers derived from invader sequences (protospacers) into CRISPR loci (forming spacers flanked by repeats), CRISPR-Cas systems are able to store the memory of past immunological encounters. While CRISPR-Cas systems have evolved in response to invading mobile genetic elements, invaders have also developed mechanisms to avoid detection. As a result of an arms race between CRISPR-Cas systems and their targets, CRISPR arrays typically undergo rapid turnover of spacers through the acquisition and loss events. Additionally, microbiomes of different individuals rarely share spacers. Here, we present a computational pipeline, CRISPRtrack, for strain tracking based on CRISPR spacer content, and we applied it to fecal transplantation microbiome data to study the retention of donor strains in recipients. Our results demonstrate the potential use of CRISPRs as a simple yet effective tool for donor-strain tracking in fecal transplantation and as a general purpose tool for quantifying microbiome similarity.}, }
@article {pmid30820331, year = {2019}, author = {Gundling, F and Roggenbrod, S and Schleifer, S and Sohn, M and Schepp, W}, title = {Patient perception and approval of faecal microbiota transplantation (FMT) as an alternative treatment option for obesity.}, journal = {Obesity science &amp; practice}, volume = {5}, number = {1}, pages = {68-74}, pmid = {30820331}, issn = {2055-2238}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) represents a treatment option for some diseases, e.g. recurring Clostridium difficile-associated colitis. However, there is also evidence that FMT can be effective in treating obesity. This pilot study established the approval and willingness of obese patients to undergo FMT.<br><br>METHODS: We conducted a survey of adults with obesity using a questionnaire containing 21 both multiple choice and open questions was dispatched to a cohort of 101 persons with obesity. It included questions aiming at the process of FMT itself, donors as well as possible concerns. Additionally aspects of social background and disease activity were dealt with.<br><br>RESULTS: The response rate amounted to 30.1% (n&#xa0;=&#xa0;31). In our population, mean BMI was 40.5&#xa0;kg/m[2] while the vast majority already tried out treatment modalities to lose weight before. 25.8% of persons with obesity were aware of FMT. 62.1% were willing to undergo FMT if the donor was healthy and anonymous while only 6.9% clearly refused this option. Sixty preferred an anonymous donor or a person proposed by their doctor while colonoscopy was the preferred application by 76.7%. The absence of risks of the procedure (47.8%) formed the principal motivation while reduction of medication was considered as least important reason (in 26.1). Insufficient testing of the faeces concerning infections raised the most concerns (in 61.6%).<br><br>CONCLUSION: For the majority of the persons with obesity surveyed FMT represents a treatment option. Approximately two thirds of the questionees would consider FMT as an alternative treatment option, even in spite of a satisfactory disease response to current standard therapies. Unsurprisingly there are concerns in regard to the transmission of possible infectious agents as well as to the hygieneic implementation of FMT itself.}, }
@article {pmid30817479, year = {2019}, author = {Kay, E and Hawramee, S and Pollani, S and Mandel, ED}, title = {Nonpharmacologic options for treating irritable bowel syndrome.}, journal = {JAAPA : official journal of the American Academy of Physician Assistants}, volume = {32}, number = {3}, pages = {38-42}, doi = {10.1097/01.JAA.0000553384.82884.b8}, pmid = {30817479}, issn = {1547-1896}, mesh = {*Cognitive Behavioral Therapy ; Dietary Carbohydrates/*administration &amp; dosage ; Disaccharides/administration &amp; dosage ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/diagnosis/etiology/*therapy ; Monosaccharides/administration &amp; dosage ; Polymers/administration &amp; dosage ; Probiotics/*therapeutic use ; Risk Factors ; Stress, Psychological/complications ; }, abstract = {Irritable bowel syndrome (IBS) is a chronic functional disorder with no organic cause. Risk factors are multifactorial and treatment typically consists of antimotility or stimulant laxatives and antidepressants. This article reviews several newer areas of interest: probiotics, fecal microbiota transplant, a low FODMAP diet, and cognitive behavioral therapy.}, }
@article {pmid30816855, year = {2019}, author = {Mullish, BH and McDonald, JAK and Pechlivanis, A and Allegretti, JR and Kao, D and Barker, GF and Kapila, D and Petrof, EO and Joyce, SA and Gahan, CGM and Glegola-Madejska, I and Williams, HRT and Holmes, E and Clarke, TB and Thursz, MR and Marchesi, JR}, title = {Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection.}, journal = {Gut}, volume = {68}, number = {10}, pages = {1791-1800}, pmid = {30816855}, issn = {1468-3288}, support = {MC_PC_17162/MRC_/Medical Research Council/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; 107660/Z/15Z/WT_/Wellcome Trust/United Kingdom ; MR/P028225/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Amidohydrolases/*pharmacology ; Animals ; Clostridioides difficile/*genetics ; Clostridium Infections/microbiology/*therapy ; DNA, Bacterial/*genetics ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Glycocholic Acid ; Humans ; Mice ; Mice, Inbred C57BL ; Recurrence ; Tandem Mass Spectrometry ; }, abstract = {OBJECTIVE: Faecal microbiota transplant (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect C. difficile germination or vegetative growth. We hypothesised that loss of gut microbiota-derived bile salt hydrolases (BSHs) predisposes to CDI by perturbing gut bile metabolism, and that BSH restitution is a key mediator of FMT's efficacy in treating the condition.<br><br>DESIGN: Using stool collected from patients and donors pre-FMT/post-FMT for rCDI, we performed 16S rRNA gene sequencing, ultra performance liquid chromatography mass spectrometry (UPLC-MS) bile acid profiling, BSH activity measurement, and qPCR of bsh/baiCD genes involved in bile metabolism. Human data were validated in C. difficile batch cultures and a C57BL/6 mouse model of rCDI.<br><br>RESULTS: From metataxonomics, pre-FMT stool demonstrated a reduced proportion of BSH-producing bacterial species compared with donors/post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA, a potent C. difficile germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and bsh/baiCD gene copy number compared with pretreatment (p<0.05). In batch cultures, supernatant from engineered bsh-expressing E. coli and naturally BSH-producing organisms (Bacteroides ovatus, Collinsella aerofaciens, Bacteroides vulgatus and Blautia obeum) reduced TCA-mediated C. difficile germination relative to culture supernatant of wild-type (BSH-negative) E. coli. C. difficile total viable counts were ~70% reduced in an rCDI mouse model after administration of E. coli expressing highly active BSH relative to mice administered BSH-negative E. coli (p<0.05).<br><br>CONCLUSION: Restoration of gut BSH functionality contributes to the efficacy of FMT in treating rCDI.}, }
@article {pmid30815845, year = {2019}, author = {Zhou, ZL and Jia, XB and Sun, MF and Zhu, YL and Qiao, CM and Zhang, BP and Zhao, LP and Yang, Q and Cui, C and Chen, X and Shen, YQ}, title = {Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson's Disease Mice via Gut Microbiota and Metabolites.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {16}, number = {3}, pages = {741-760}, pmid = {30815845}, issn = {1878-7479}, mesh = {Animals ; Blotting, Western ; Brain Chemistry ; Brain-Derived Neurotrophic Factor/analysis ; Corpus Striatum/chemistry ; Dopamine/analysis/metabolism ; Enzyme-Linked Immunosorbent Assay ; *Fasting/physiology ; Fluorescent Antibody Technique ; *Gastrointestinal Microbiome/genetics/physiology ; Interleukin-1beta/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Parkinsonian Disorders/diet therapy/*prevention &amp; control ; RNA, Ribosomal, 16S/genetics ; RNA, Ribosomal, 18S/genetics ; Serotonin/analysis/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Parkinson's disease (PD) is strongly associated with life style, especially dietary habits, which have gained attention as disease modifiers. Here, we report a fasting mimicking diet (FMD), fasting 3 days followed by 4 days of refeeding for three 1-week cycles, which accelerated the retention of motor function and attenuated the loss of dopaminergic neurons in the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mice. Levels of brain-derived neurotrophic factor (BDNF), known to promote the survival of dopaminergic neurons, were increased in PD mice after FMD, suggesting an involvement of BDNF in FMD-mediated neuroprotection. Furthermore, FMD decreased the number of glial cells as well as the release of TNF-α and IL-1β in PD mice, showing that FMD also inhibited neuro-inflammation. 16S and 18S rRNA sequencing of fecal microbiota showed that FMD treatment modulated the shifts in gut microbiota composition, including higher abundance of Firmicutes, Tenericutes, and Opisthokonta and lower abundance of Proteobacteria at the phylum level in PD mice. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry revealed that FMD modulated the MPTP-induced lower propionic acid and isobutyric acid, and higher butyric acid and valeric acid and other metabolites. Transplantation of fecal microbiota, from normal mice with FMD treatment to antibiotic-pretreated PD mice increased dopamine levels in the recipient PD mice, suggesting that gut microbiota contributed to the neuroprotection of FMD for PD. These findings demonstrate that FMD can be a new means of preventing and treating PD through promoting a favorable gut microbiota composition and metabolites.}, }
@article {pmid30815766, year = {2019}, author = {Abu-Sbeih, H and Ali, FS and Wang, Y}, title = {Clinical Review on the Utility of Fecal Microbiota Transplantation in Immunocompromised Patients.}, journal = {Current gastroenterology reports}, volume = {21}, number = {4}, pages = {8}, pmid = {30815766}, issn = {1534-312X}, mesh = {AIDS-Related Opportunistic Infections/immunology/therapy ; Clostridium Infections/immunology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; *Immunocompromised Host ; Immunosuppressive Agents/adverse effects ; Tissue Transplantation/adverse effects ; }, abstract = {Fecal microbiota transplantation (FMT) represents a promising management modality for Clostridium difficile infection (CDI). In immunocompromised patients, FMT is utilized for CDI as well as emerging non-CDI indications such as inflammatory bowel disease and graft versus host disease. PURPOSE OF REVIEW: This review aims to shed light on the safety and efficacy of FMT in immunocompromised patients, including patients suffering for human immunodeficiency virus infection, solid organ and hematopoietic stem cell transplant recipients, cancer patients, and patients on immunosuppressive therapies. RECENT FINDINGS: Though the body of evidence concerning the use of FMT in immunocompromised is growing, no clinical trials exist to date. Present literature weighs in favor of FMT in immunocompromised patients, with an acceptable adverse effect profile and minimal risk of infectious adverse events. Further large scale studies and randomized controlled trials to validate the utility of FMT in immunocompromised individuals will be a welcomed endeavor.}, }
@article {pmid30813323, year = {2019}, author = {Wahlgren, M and Axenstrand, M and Håkansson, &#xc5; and Marefati, A and Lomstein Pedersen, B}, title = {In Vitro Methods to Study Colon Release: State of the Art and An Outlook on New Strategies for Better In-Vitro Biorelevant Release Media.}, journal = {Pharmaceutics}, volume = {11}, number = {2}, pages = {}, pmid = {30813323}, issn = {1999-4923}, support = {Nextbioform//VINNOVA/ ; 11//VINNOVA/ ; }, abstract = {The primary focus of this review is a discussion regarding in vitro media for colon release, but we also give a brief overview of colon delivery and the colon microbiota as a baseline for this discussion. The large intestine is colonized by a vast number of bacteria, approximately 10[12] per gram of intestinal content. The microbial community in the colon is complex and there is still much that is unknown about its composition and the activity of the microbiome. However, it is evident that this complex microbiota will affect the release from oral formulations targeting the colon. This includes the release of active drug substances, food supplements, and live microorganisms, such as probiotic bacteria and bacteria used for microbiota transplantations. Currently, there are no standardized colon release media, but researchers employ in vitro models representing the colon ranging from reasonable simple systems with adjusted pH with or without key enzymes to the use of fecal samples. In this review, we present the pros and cons for different existing in vitro models. Furthermore, we summarize the current knowledge of the colonic microbiota composition which is of importance to the fermentation capacity of carbohydrates and suggest a strategy to choose bacteria for a new more standardized in vitro dissolution medium for the colon.}, }
@article {pmid30810508, year = {2019}, author = {Falony, G and Vandeputte, D and Caenepeel, C and Vieira-Silva, S and Daryoush, T and Vermeire, S and Raes, J}, title = {The human microbiome in health and disease: hype or hope.}, journal = {Acta clinica Belgica}, volume = {74}, number = {2}, pages = {53-64}, doi = {10.1080/17843286.2019.1583782}, pmid = {30810508}, issn = {2295-3337}, mesh = {Colon/microbiology ; Disease ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {OBJECTIVES: The prognostic, diagnostic, and therapeutic potential of the human gut microbiota is widely recognised. However, translation of microbiome findings to clinical practice is challenging. Here, we discuss current knowledge and applications in the field.<br><br>METHODS: We revisit some recent advances in the field of faecal microbiome analyses with a focus on covariate analyses and ecological interpretation.<br><br>RESULTS: Population-level characterization of gut microbiota variation among healthy volunteers has allowed identifying microbiome covariates required for clinical studies. Currently, microbiome research is moving from relative to quantitative approaches that will shed a new light on microbiota-host interactions in health and disease.<br><br>CONCLUSIONS: Covariate characterization and technical advances increase reproducibility of microbiome research. Targeted in vitro/in vivo intervention studies will accelerate clinical implementation of microbiota findings.}, }
@article {pmid30809523, year = {2019}, author = {Ohkusa, T and Koido, S and Nishikawa, Y and Sato, N}, title = {Gut Microbiota and Chronic Constipation: A Review and Update.}, journal = {Frontiers in medicine}, volume = {6}, number = {}, pages = {19}, pmid = {30809523}, issn = {2296-858X}, abstract = {Background: Chronic constipation, including functional constipation and constipation-type irritable bowel syndrome, is a prevalent, multifactorial gastrointestinal disorder, and its etiology and pathophysiology remain poorly understood. Recently studies using 16S rRNA-based microbiota profiling have demonstrated dysbiosis of gut microbiota in chronic constipation. Aims: To provide an overview of recent studies for microbiota in chronic constipation and treatments for chronic constipation using probiotics, prebiotics, synbiotics, antibiotics and fecal microbiota transplantation (FMT). Methods: PubMed searches were performed up to 1 August 2018 using keywords: "IBS," "IBS-C," "irritable bowel syndrome," "irritable bowel syndrome with constipation," "functional constipation," "chronic constipation" in combination with "gut microbiota," "dysbiosis," "gut microflora" for microbiota in chronic constipation, and in combination with "probiotics," "prebiotics," "synbiotics," "antibiotics," and "fecal microbiota transplantation." Results: The findings of gut microbiota in functional constipation are inconsistent, and currently no consensus exists. Although no clear consensus exists, compared with healthy subjects, IBS-C patients have a lower level of Actinobacteria, including Bifidobacteria, in their fecal samples and a higher level of Bacteroidetes in their mucosa. In most randomized controlled and parallel-group trials, probiotics, prebiotics, synbiotics, antibiotics, and FMT therapy for chronic constipation were effective with few side effects. However, there are many studies in a small number and the types of probiotics are different, it is difficult to evaluate the effect. Conclusions: Evidence indicates that dysbiosis of gut microbiota may contribute to functional constipation and constipation-type irritable bowel syndrome. Targeting treatments for the dysbiosis of constipation by probiotics, prebiotics, synbiotics, antibiotics, and FMT may be a new option, especially for refractory constipation to conventional therapies.}, }
@article {pmid30809438, year = {2019}, author = {Li, Y and Zou, Z and Bian, X and Huang, Y and Wang, Y and Yang, C and Zhao, J and Xie, L}, title = {Fecal microbiota transplantation research output from 2004 to 2017: a bibliometric analysis.}, journal = {PeerJ}, volume = {7}, number = {}, pages = {e6411}, pmid = {30809438}, issn = {2167-8359}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging therapy against Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). Although the therapy has gained prominence, there has been no bibliometric analysis of FMT.<br><br>METHODS: Studies published from 2004 to 2017 were extracted from the Science Citation Index Expanded. Bibliometric analysis was used to evaluate the number or cooperation network of publications, countries, citations, references, journals, authors, institutions and keywords.<br><br>RESULTS: A total of 796 items were included, showing an increasing trend annually. Publications mainly came from 10 countries, led by the US (n&#xa0;=&#xa0;363). In the top 100 articles ranked by the number of citations (range 47-1,158), American Journal of Gastroenterology (2017 IF = 10.231) took the top spot. The co-citation network had 7 co-citation clusters headed by 'recurrent Clostridium difficile infection'. The top 7 keywords with the strongest citation bursts had three parts, 'microbiota', ' diarrhea ', and 'case series'. All keywords were divided into four domains, 'disease', 'nosogenesis', 'trial', and 'therapy'.<br><br>CONCLUSIONS: This study shows the research performance of FMT from 2004 to 2017 and helps investigators master the trend of FMT, which is also an ongoing hotspot of research.}, }
@article {pmid30807838, year = {2019}, author = {Sougiannis, AT and VanderVeen, BN and Enos, RT and Velazquez, KT and Bader, JE and Carson, M and Chatzistamou, I and Walla, M and Pena, MM and Kubinak, JL and Nagarkatti, M and Carson, JA and Murphy, EA}, title = {Impact of 5 fluorouracil chemotherapy on gut inflammation, functional parameters, and gut microbiota.}, journal = {Brain, behavior, and immunity}, volume = {80}, number = {}, pages = {44-55}, pmid = {30807838}, issn = {1090-2139}, support = {K00 CA234920/CA/NCI NIH HHS/United States ; K99 AT009206/AT/NCCIH NIH HHS/United States ; R00 AT009206/AT/NCCIH NIH HHS/United States ; P20 GM103641/GM/NIGMS NIH HHS/United States ; F31 AT009820/AT/NCCIH NIH HHS/United States ; P30 GM103336/GM/NIGMS NIH HHS/United States ; F99 CA234920/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Azoxymethane ; Colitis/chemically induced ; Colon/metabolism ; Colonic Neoplasms ; Colorectal Neoplasms/chemically induced/metabolism/microbiology ; Dextran Sulfate ; Disease Models, Animal ; Fecal Microbiota Transplantation/methods ; Fluorouracil/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Inflammation/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {Emerging evidence suggests that gut microbiota may influence the response to chemotherapy. We sought to characterize the effects of 5 fluorouracil (5FU) chemotherapy on colon inflammation and functional measures in colorectal cancer (CRC) and to further determine whether gut microbiota can influence this response. 50 C57BL/6 were randomized into four groups; Control + Vehicle (n = 10), Control + 5FU (n = 10), AOM/DSS + Vehicle (n = 15), and AOM/DSS + 5FU (n = 15). CRC was induced chemically by a single 10 mg/kg injection of azoxymethane (AOM) followed by two cycles (2% and 1%) of dextran sodium sulfate (DSS). Mice were then treated with 3 cycles of vehicle or 5FU (cycle 1: 40 mg/kg, cycle 2 + 3: 20 mg/kg). Functional tests (grip strength and run-to-fatigue) were performed prior to 5FU treatment (baseline) and at the completion of the second cycle of 5FU. Following the third 5FU cycle, mice were euthanized and the colon was evaluated for expression of inflammatory genes using RT-qPCR and stool samples were profiled using 16S rRNA sequencing. A second experiment used fecal microbiota transplantation from 5FU treated mice to control mice (n = 10-15/group) to determine whether 5FU associated changes in the microbiota could influence functional measures and colon inflammation. 5FU reduced grip strength (p < 0.05) and caused a trending decrease in run-to-fatigue performance in cancer mice (p = 0.06). Select intestinal inflammatory genes were significantly elevated with 5FU treatment and this was further exacerbated with cancer (p < 0.05). Microbiota analysis revealed increased dissimilarity and alterations in bacterial taxonomy in 5FU and AOM/DSS-treated mice (p < 0.05). Fecal transplant from 5FU treated mice reduced functional performance (p < 0.05) and altered select colon inflammatory markers (p < 0.05). This study provides evidence of an effect of 5FU on inflammatory responses and functional measures in a mouse model of CRC and suggests that gut microbes may play a role in some, but not all, 5FU related perturbations.}, }
@article {pmid30804820, year = {2019}, author = {Cheung, SG and Goldenthal, AR and Uhlemann, AC and Mann, JJ and Miller, JM and Sublette, ME}, title = {Systematic Review of Gut Microbiota and Major Depression.}, journal = {Frontiers in psychiatry}, volume = {10}, number = {}, pages = {34}, pmid = {30804820}, issn = {1664-0640}, support = {P50 MH090964/MH/NIMH NIH HHS/United States ; R01 AI116939/AI/NIAID NIH HHS/United States ; }, abstract = {Background: Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder (MDD). Bacterial transplantation from MDD patients to rodents produces depression-like behaviors. In humans, case-control studies have examined the gut microbiome in healthy and affected individuals. We systematically reviewed existing studies comparing gut microbial composition in MDD and healthy volunteers. Methods: A PubMed literature search combined the terms "depression," "depressive disorder," "stool," "fecal," "gut," and "microbiome" to identify human case-control studies that investigated relationships between MDD and microbiota quantified from stool. We evaluated the resulting studies, focusing on bacterial taxa that were different between MDD and healthy controls. Results: Six eligible studies were found in which 50 taxa exhibited differences (p < 0.05) between patients with MDD and controls. Patient characteristics and methodologies varied widely between studies. Five phyla-Bacteroidetes, Firmicutes, Actinobacteria, Fusobacteria, and Protobacteria-were represented; however, divergent results occurred across studies for all phyla. The largest number of differentiating taxa were within phylum Firmicutes, in which nine families and 12 genera differentiated the diagnostic groups. The majority of these families and genera were found to be statistically different between the two groups in two identified studies. Family Lachnospiraceae differentiated the diagnostic groups in four studies (with an even split in directionality). Across all five phyla, nine genera were higher in MDD (Anaerostipes, Blautia, Clostridium, Klebsiella, Lachnospiraceae incertae sedis, Parabacteroides, Parasutterella, Phascolarctobacterium, and Streptococcus), six were lower (Bifidobacterium, Dialister, Escherichia/Shigella, Faecalibacterium, and Ruminococcus), and six were divergent (Alistipes, Bacteroides, Megamonas, Oscillibacter, Prevotella, and Roseburia). We highlight mechanisms and products of bacterial metabolism as they may relate to the etiology of depression. Conclusions: No consensus has emerged from existing human studies of depression and gut microbiome concerning which bacterial taxa are most relevant to depression. This may in part be due to differences in study design. Given that bacterial functions are conserved across taxonomic groups, we propose that studying microbial functioning may be more productive than a purely taxonomic approach to understanding the gut microbiome in depression.}, }
@article {pmid30803212, year = {2019}, author = {Esteghamati, A and Khanaliha, K and Bokharaei-Salim, F and Sayyahfar, S and Ghaderipour, M}, title = {Prevalence of Intestinal Parasitic Infection in Cancer, Organ Transplant and Primary Immunodeficiency Patients in Tehran, Iran.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {20}, number = {2}, pages = {495-501}, pmid = {30803212}, issn = {2476-762X}, mesh = {Adolescent ; Adult ; Aged ; Animals ; Child ; Child, Preschool ; Cross-Sectional Studies ; Feces/*parasitology ; Female ; Follow-Up Studies ; Humans ; Immunologic Deficiency Syndromes/*complications ; Intestinal Diseases, Parasitic/*epidemiology/parasitology ; Iran/epidemiology ; Male ; Middle Aged ; Neoplasms/*complications ; Organ Transplantation/*adverse effects ; Parasites/*isolation &amp; purification ; Prevalence ; Prognosis ; Young Adult ; }, abstract = {Background: Intestinal parasitic infection in immunodeficient patients especially those with impaired cellular immunity, like neoplasia, renal or heart transplant needs careful consideration. The objective of this study is to evaluate the prevalence of intestinal parasites in different group of patients including cancer patients; organ transplants recipients, and primary immunodeficiency patients. Methods: Stool samples from 190 patients including 80 patients with Primary Immunodeficiency, 85 cancer patients and 25 organ transplant recipients were collected; a direct examination with Phosphate buffered saline (PBS) and formalin ether concentration was performed. The DNA was extracted from parasitologically confirmed patients and nested PCR and sequencing was performed and new obtained sequences of Cryptosporidium parvum and Enterocytozoon bieneusi were compared with deposited ones. Results: In general, the prevalence of parasites was 26/80 (32.5%) in primary immunodeficiency, 22/85(25.9%) in cancer group, and 7/25 (28%) in organ transplant. The prevalence of intestinal parasitic infections in primary immunodeficiency patients were Blastocystis hominis 13 (16.2%), Giardia lamblia 10 (12.5%), Cryptosporidium 1(1.2%), Chilomastix mesnilii 1 (1.2%), Dientamoeba fragilis 1(1.2%). Of 25 organ transplants, 6 (24%) Cryptosporidium sp were found, all of which were confirmed as Cryptosporidium parvum and one case of Microspora in a heart transplant recipient was confirmed as Enterocytozoon bieneusi by PCR sequencing. The predominant intestinal parasitic infection in cancer patients was 19 (22.3%) Blastocystis hominis followed by two (2.3%) Giardia lamblia and one Dientamoeba fragilis 1 (1.1%). Conclusion: The high rate of infection with Blastocystis hominis was found in cancer patients especially colorectal cancer patients, so careful consideration should be given by physicians. Cryptosporidium sp was found to be the major cause of parasitic intestinal infection in patients with organ transplant compared to primary immunodeficiency patients; so transplant recipients undergoing immunosuppressive therapy should be considered as a risk group for acquiring microsporidiosis and Cryptosporidium infection.}, }
@article {pmid30803179, year = {2019}, author = {Mo, R and Ren, RR and Zhang, XW and Yang, YS}, title = {[Fecal microbiota transplantation for the treatment of ulcerative colitis: a Meta-analysis].}, journal = {Zhonghua nei ke za zhi}, volume = {58}, number = {3}, pages = {202-208}, doi = {10.3760/cma.j.issn.0578-1426.2019.03.010}, pmid = {30803179}, issn = {0578-1426}, support = {2015AA020701//National High Technology Research and Development Program of China/ ; }, mesh = {Colitis, Ulcerative/*microbiology/*therapy ; *Drug-Related Side Effects and Adverse Reactions ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Gastrointestinal Microbiome ; Humans ; Inclusion Bodies ; Microbiota ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {Objective: We aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the treatment of ulcerative colitis (UC) in this Meta-analysis. Methods: Literature related to FMT for the treatment of UC from PubMed, Embase, Cochrane databases, CNKI, VIP and Wanfang Data were searched and screened with update study in May 2018. Two independent investigators extracted information according to inclusion and exclusion criteria. The Meta-analysis was conducted by Stata 12.0 software. Results: A total of 4 randomized controlled trials (RCTs) and 19 non-randomized controlled trials (non-RCTs) including 536 participants met the inclusion criteria. Meta-analysis of RCTs showed that FMT significantly increased the clinical remission rate (OR=2.47, 95%CI 1.40-4.33, P=0.02) and clinical response rate (OR=1.86, 95%CI 1.15-3.02, P=0.01) in UC patients without increasing the incidence of severe adverse effects (OR=1.40, 95%CI 0.51-3.79, P=0.51). The results from 19 non-RCTs showed that clinical remission rate in UC patients with FMT treatment was 20%(95%CI 13%-28%) and the clinical response rate was 50%(95%CI 36%-65%). All adverse events were graded as mild and self-resolving. No FMT-related severe adverse effects were reported. Conclusions: Our analysis suggests that FMT is a safe and effective method for the treatment of UC. Considering several limitations of this Meta-analysis and previous clinical trials, further large-scale multicenter RCTs are still required to further verify the conclusion.}, }
@article {pmid30800106, year = {2019}, author = {Bodkhe, R and Shetty, SA and Dhotre, DP and Verma, AK and Bhatia, K and Mishra, A and Kaur, G and Pande, P and Bangarusamy, DK and Santosh, BP and Perumal, RC and Ahuja, V and Shouche, YS and Makharia, GK}, title = {Comparison of Small Gut and Whole Gut Microbiota of First-Degree Relatives With Adult Celiac Disease Patients and Controls.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {164}, pmid = {30800106}, issn = {1664-302X}, abstract = {Recent studies on celiac disease (CeD) have reported alterations in the gut microbiome. Whether this alteration in the microbial community is the cause or effect of the disease is not well understood, especially in adult onset of disease. The first-degree relatives (FDRs) of CeD patients may provide an opportunity to study gut microbiome in pre-disease state as FDRs are genetically susceptible to CeD. By using 16S rRNA gene sequencing, we observed that ecosystem level diversity measures were not significantly different between the disease condition (CeD), pre-disease (FDR) and control subjects. However, differences were observed at the level of amplicon sequence variant (ASV), suggesting alterations in specific ASVs between pre-disease and diseased condition. Duodenal biopsies showed higher differences in ASVs compared to fecal samples indicating larger disruption of the microbiota at the disease site. The duodenal microbiota of FDR was characterized by significant abundance of ASVs belonging to Parvimonas, Granulicatella, Gemella, Bifidobacterium, Anaerostipes, and Actinomyces genera. The duodenal microbiota of CeD was characterized by higher abundance of ASVs from genera Megasphaera and Helicobacter compared to the FDR microbiota. The CeD and FDR fecal microbiota had reduced abundance of ASVs classified as Akkermansia and Dorea when compared to control group microbiota. In addition, predicted functional metagenome showed reduced ability of gluten degradation by CeD fecal microbiota in comparison to FDRs and controls. The findings of the present study demonstrate differences in ASVs and predicts reduced ability of CeD fecal microbiota to degrade gluten compared to the FDR fecal microbiota. Further research is required to investigate the strain level and active functional profiles of FDR and CeD microbiota to better understand the role of gut microbiome in pathophysiology of CeD.}, }
@article {pmid30796005, year = {2019}, author = {Papanicolas, LE and Choo, JM and Wang, Y and Leong, LEX and Costello, SP and Gordon, DL and Wesselingh, SL and Rogers, GB}, title = {Bacterial viability in faecal transplants: Which bacteria survive?.}, journal = {EBioMedicine}, volume = {41}, number = {}, pages = {509-516}, pmid = {30796005}, issn = {2352-3964}, mesh = {Acetates/metabolism ; Bacteria/genetics/isolation &amp; purification/*metabolism ; Bacterial Proteins/genetics ; Butyrates/metabolism ; Coenzyme A-Transferases/genetics ; Fatty Acids, Volatile/biosynthesis ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Freezing ; Gastrointestinal Microbiome ; Humans ; Microbial Viability ; RNA, Ribosomal, 16S/chemistry/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The therapeutic potential of faecal microbiota transplantation (FMT) is under investigation for a range of inflammatory conditions. While mechanisms of benefit are poorly understood, most models rely on the viability of transplanted microbes. We hypothesised that protocols commonly used in the preparation of faecal transplants will substantially reduce the number, diversity and functional potential of viable microbes.<br><br>METHODS: Stools from eight screened donors were processed under strict anaerobic conditions, in ambient air, and freeze-thawed. Propidium monoazide (PMA) sample treatment was combined with quantitative PCR, 16S rRNA gene amplicon sequencing and short-chain fatty acid (SCFA) analysis to define the viable microbiota composition and functional potential.<br><br>FINDINGS: Approximately 50% of bacterial content of stool processed immediately under strict anaerobic conditions was non-viable. Homogenisation in ambient air or freeze-thaw reduced viability to 19% and 23% respectively. Processing of samples in ambient air resulted in up to 12-fold reductions in the abundance of important commensal taxa, including the highly butyrogenic species Faecalibacterium prausnitzii, Subdoligranulum variable, and Eubacterium hallii. The adverse impact of atmospheric oxygen exposure on the capacity of the transplanted microbiota to support SCFA biosynthesis was demonstrated by significantly reduced butyrate and acetate production by faecal slurries processed in ambient air. In contrast, while reducing overall levels of viable bacteria, freeze-thaw did not significantly alter viable microbiota composition.<br><br>INTERPRETATION: The practice of preparing material for faecal transplantation in ambient air profoundly affects viable microbial content, disproportionately reducing the abundance of anaerobic commensals and the capacity for biosynthesis of important anti-inflammatory metabolites. FUND: This work was supported by the South Australian Health and Medical Research Institute. LP is supported by a scholarship from the Flinders Foundation. GR is supported by a Matthew Flinders Research Fellowship.}, }
@article {pmid30792981, year = {2019}, author = {Shin, W and Wu, A and Massidda, MW and Foster, C and Thomas, N and Lee, DW and Koh, H and Ju, Y and Kim, J and Kim, HJ}, title = {A Robust Longitudinal Co-culture of Obligate Anaerobic Gut Microbiome With Human Intestinal Epithelium in an Anoxic-Oxic Interface-on-a-Chip.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {7}, number = {}, pages = {13}, pmid = {30792981}, issn = {2296-4185}, abstract = {The majority of human gut microbiome is comprised of obligate anaerobic bacteria that exert essential metabolic functions in the human colon. These anaerobic gut bacteria constantly crosstalk with the colonic epithelium in a mucosal anoxic-oxic interface (AOI). However, in vitro recreation of the metabolically mismatched colonic AOI has been technically challenging. Furthermore, stable co-culture of the obligate anaerobic commensal microbiome and epithelial cells in a mechanically dynamic condition is essential for demonstrating the host-gut microbiome crosstalk. Here, we developed an anoxic-oxic interface-on-a-chip (AOI Chip) by leveraging a modified human gut-on-a-chip to demonstrate a controlled oxygen gradient in the lumen-capillary transepithelial interface by flowing anoxic and oxic culture medium at various physiological milieus. Computational simulation and experimental results revealed that the presence of the epithelial cell layer and the flow-dependent conditioning in the lumen microchannel is necessary and sufficient to create the steady-state vertical oxygen gradient in the AOI Chip. We confirmed that the created AOI does not compromise the viability, barrier function, mucin production, and the expression and localization of tight junction proteins in the 3D intestinal epithelial layer. Two obligate anaerobic commensal gut microbiome, Bifidobacterium adolescentis and Eubacterium hallii, that exert metabolic cross-feeding in vivo, were independently co-cultured with epithelial cells in the AOI Chip for up to a week without compromising any cell viability. Our new protocol for creating an AOI in a microfluidic gut-on-a-chip may enable to demonstrate the key physiological interactions of obligate anaerobic gut microbiome with the host cells associated with intestinal metabolism, homeostasis, and immune regulation.}, }
@article {pmid30791840, year = {2019}, author = {Lauro, A and Lacaille, F}, title = {Short bowel syndrome in children and adults: from rehabilitation to transplantation.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {13}, number = {1}, pages = {55-70}, doi = {10.1080/17474124.2019.1541736}, pmid = {30791840}, issn = {1747-4132}, mesh = {Adult ; Age Factors ; Child ; Child, Preschool ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Intestinal Absorption ; Intestines/microbiology/physiopathology/*transplantation ; Nutritional Status ; *Parenteral Nutrition/adverse effects ; Recovery of Function ; Risk Factors ; Short Bowel Syndrome/epidemiology/physiopathology/*rehabilitation/*surgery ; Treatment Outcome ; }, abstract = {Short bowel syndrome (SBS) is a dramatic clinical condition in both children and adults; the residual bowel length is not sufficient to avoid intestinal failure, with subsequent malnutrition and growth retardation, and intravenous support is required to provide the nutrients normally coming from the intestine. Apart from the primary disease, the medical status can be worsened by complications of intestinal failure: if there are irreversible, the prognosis is poor unless a successful intestinal rehabilitation is achieved. Areas covered: The rescue of the remnant small bowel requires a multidisciplinary expertise to achieve digestive autonomy. The use of intestinal trophic factors has shown encouraging results in improving the intestinal adaptation process. Whenever the residual bowel length is inadequate, in a well-selected population weaning parenteral nutrition (PN) off could be attempted by surgery through lengthening procedures. A further subset of patients, with total and irreversible intestinal failure and severe complications on PN, may have an indication to intestinal transplantation. This procedure is still affected by poor long-term results. Expert commentary: Novel approaches developed through a multidisciplinary team work, such as manipulation of microbiota or tissue bioengineering, should be added to current therapies to treat successfully SBS.}, }
@article {pmid30791837, year = {2019}, author = {Hatton, G and Shawcross, DL}, title = {Is treating the gut microbiome the key to achieving better outcomes in cirrhosis?.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {13}, number = {1}, pages = {1-2}, doi = {10.1080/17474124.2019.1543587}, pmid = {30791837}, issn = {1747-4132}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Bacteria/*drug effects/growth &amp; development/immunology ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Humans ; Immunity, Innate ; Intestines/*drug effects/immunology/microbiology ; Liver Cirrhosis/diagnosis/immunology/microbiology/*therapy ; Probiotics/adverse effects/*therapeutic use ; Treatment Outcome ; }, }
@article {pmid30791767, year = {2019}, author = {Suk, KT and Kim, DJ}, title = {Gut microbiota: novel therapeutic target for nonalcoholic fatty liver disease.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {13}, number = {3}, pages = {193-204}, doi = {10.1080/17474124.2019.1569513}, pmid = {30791767}, issn = {1747-4132}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Bacteria/*drug effects/growth &amp; development ; *Dietary Supplements/adverse effects ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Gastrointestinal Microbiome/*drug effects ; Host Microbial Interactions ; Humans ; Intestines/*drug effects/microbiology ; Non-alcoholic Fatty Liver Disease/diagnosis/epidemiology/microbiology/*therapy ; Prebiotics ; Prevalence ; Probiotics/therapeutic use ; Risk Factors ; Synbiotics ; Treatment Outcome ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) is one of the most common and increasing liver diseases worldwide with a prevalence of 20-33%. NAFLD may progress to fibrosis, compensated cirrhosis, advanced cirrhosis, or hepatocellular carcinoma. Despite the increasing prevalence of NAFLD, definitive medical treatment has not been established, with the exception of lifestyle modification with exercise. Because of the direct connection via portal vein between the intestines and the liver (gut-gut microbiota-liver axis), gut microbiota and associated dysbiosis have been known as regulators in the pathophysiology of NAFLD. Area covered: New therapeutic approaches for modulation of gut microbiota have been proposed and the effectiveness of new therapies including probiotics, prebiotics, synbiotics, bile acid regulation, absorbent, and fecal microbiota transplantation have been demonstrated in recent several studies. This review focuses on the available evidences for new therapies modulating gut microbiota in the management and the prevention of NAFLD. Expert commentary: Gut-gut microbiota-liver axis may play an important role in the etiology of many liver diseases, including NAFLD. It is logical to seek the manipulation of this axis, and further studies are required to understand the underlying precise mechanisms of microbiota-modulation on NAFLD.}, }
@article {pmid30789675, year = {2019}, author = {Stern, JM and Urban-Maldonado, M and Usyk, M and Granja, I and Schoenfeld, D and Davies, KP and Agalliu, I and Asplin, J and Burk, R and Suadicani, SO}, title = {Fecal transplant modifies urine chemistry risk factors for urinary stone disease.}, journal = {Physiological reports}, volume = {7}, number = {4}, pages = {e14012}, pmid = {30789675}, issn = {2051-817X}, support = {R21 DK108097/DK/NIDDK NIH HHS/United States ; NIH R21 DK108097-02/NH/NIH HHS/United States ; }, mesh = {Animals ; Calcium/urine ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Absorption ; Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Zucker ; Urinary Calculi/prevention &amp; control/*therapy ; Urine/chemistry/microbiology ; }, abstract = {Urinary stone disease (USD) is a major health concern. There is a need for new treatment modalities. Recently, our group provided evidence for an association between the GMB composition and USD. The accessibility of the Gut Microbiome (GMB) makes it an attractive target for investigation and therefore, in these studies we have evaluated the extent to which the whole gut microbial community in fecal transplants can affect urinary stone risk parameters in an animal model. Fresh fecal pellets were collected from Zucker lean rats, homogenized in PBS (100 mg/mL), filtered through a 70 μm strainer and then orally gavaged into C57BL/6NTac germ-free mice. Twenty-four hours urine collections and GMB analysis were performed over time for 1 month. Kidney and gut tissue were harvested from transplanted mice for western blot analysis of expression levels of the Slc26a6 transporter involved in oxalate balance. Urinary calcium decreased after fecal transplant by 55% (P < 0.001). Urinary oxalate levels were on average 24% lower than baseline levels (P < 0.001). Clostridiaceae family was negatively correlated with urinary oxalate at 4 weeks after transplant (r = -0.83, P < 0.01). There was a 0.6 unit average increase in urinary pH from a baseline of 5.85 (SE ± 0.028) to 6.49 (SE ± 0.04) (P < 0.001) after transplant. There was a concomitant 29% increase in gastrointestinal alkali absorption (P < 0.001) 4-weeks after fecal transplant. Slc26a6 expression increased by 90% in the cecum after transplant. Our results suggest that the gut microbiome may impact metabolism, alters urinary chemistry, and thereby may influence USD; the accessibility of the GMB can potentially be leveraged for therapeutic interventions.}, }
@article {pmid30783740, year = {2019}, author = {Picciariello, A and Papagni, V and Martines, G and De Fazio, M and Digennaro, R and Altomare, DF}, title = {Post-operative clinical, manometric, and defecographic findings in patients undergoing unsuccessful STARR operation for obstructed defecation.}, journal = {International journal of colorectal disease}, volume = {34}, number = {5}, pages = {837-842}, pmid = {30783740}, issn = {1432-1262}, mesh = {Anal Canal/*surgery ; *Defecography ; Humans ; Intestinal Obstruction/*physiopathology/*surgery ; *Manometry ; *Postoperative Care ; Preoperative Care ; Rectum/*surgery ; *Surgical Stapling ; Surveys and Questionnaires ; Treatment Outcome ; }, abstract = {AIM: To evaluate the reason for failure of STARR (stapled transanal rectal resection) operation for obstructed defecation.<br><br>METHODS: A retrospective study (June 2012-December 2017) was performed using a prospectively maintained database of patients who underwent STARR operation for ODS (obstructed defecation syndrome), complaining of persisting or de novo occurrence of pelvic floor dysfunctions. Postoperative St Mark's and ODS scores were evaluated. A VAS was used to score pelvic pain. Patients' satisfaction was estimated administering the CPGAS (clinical patient grading assessment scale) questionnaire. Objective evaluation was performed by dynamic proctography and anorectal manometry.<br><br>RESULTS: Ninety patients (83.3% females) operated for ODS using STARR technique were evaluated. Median ODS score was 19 while 20 patients (22%) reported de novo fecal urgency and 4 patients a worsening of their preoperative fecal incontinence. Dynamic proctography performed in 54/90 patients showed a significant (>&#x2009;3.0&#xa0;cm) rectocele in 19 patients, recto-rectal intussusception in 10 patients incomplete emptying in 24 patients. When compared with internal normal standards, anorectal manometry showed decreased rectal compliance and maximum tolerable volume in patients with urgency. Nine patients reported a persistent postoperative pelvic pain (median VAS score 6).<br><br>CONCLUSION: Failure of STARR to treat ODS, documented by persisting ODS symptoms, fecal urgency, or chronic pelvic pain, is often justified by the persistence or de novo onset of alteration of the anorectal anatomy at defecation. This occurs in about half of the patients, but in 40% of the cases who complained of incomplete emptying or incontinence, anatomical abnormalities were not recognized.}, }
@article {pmid30783183, year = {2019}, author = {Khan, N and Mendonca, L and Dhariwal, A and Fontes, G and Menzies, D and Xia, J and Divangahi, M and King, IL}, title = {Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis.}, journal = {Mucosal immunology}, volume = {12}, number = {3}, pages = {772-783}, pmid = {30783183}, issn = {1935-3456}, support = {MOP-130579//CIHR/Canada ; FDN-143273//CIHR/Canada ; }, mesh = {Animals ; Antibiotics, Antitubercular/*therapeutic use ; Disease Models, Animal ; Drug-Related Side Effects and Adverse Reactions/*immunology ; Dysbiosis/etiology/*immunology ; Gastrointestinal Microbiome/drug effects/*physiology ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/drug effects ; Immunomodulation ; Isoniazid/therapeutic use ; Macrophages, Alveolar/drug effects/*metabolism ; Mice ; Mice, Inbred C57BL ; Mycobacterium tuberculosis/*physiology ; Pyrazinamide/therapeutic use ; Rifampin/therapeutic use ; Tuberculosis, Pulmonary/*drug therapy ; }, abstract = {Current treatments for tuberculosis (TB) are effective in controlling Mycobacterium tuberculosis (Mtb) growth, yet have significant side effects and do not prevent reinfection. Therefore, it is critical to understand why our host defense system is unable to generate permanent immunity to Mtb despite prolonged anti-tuberculosis therapy (ATT). Here, we demonstrate that treatment of mice with the most widely used anti-TB drugs, rifampicin (RIF) or isoniazid (INH) and pyrazinamide (PYZ), significantly altered the composition of the gut microbiota. Unexpectedly, treatment of mice with the pro-Mtb drugs INH and PYZ, but not RIF, prior to Mtb infection resulted in an increased bacterial burden, an effect that was reversible by fecal transplantation from untreated animals. Mechanistically, susceptibility of INH/PYZ-treated mice was associated with impaired metabolism of alveolar macrophages and defective bactericidal activity. Collectively, these data indicate that dysbiosis induced by ATT administered to millions of individuals worldwide may have adverse effects on the anti-Mtb response of alveolar macrophages.}, }
@article {pmid30782287, year = {2019}, author = {Aabed, K and Shafi Bhat, R and Moubayed, N and Al-Mutiri, M and Al-Marshoud, M and Al-Qahtani, A and Ansary, A}, title = {Ameliorative effect of probiotics (Lactobacillus paracaseii and Protexin®) and prebiotics (propolis and bee pollen) on clindamycin and propionic acid-induced oxidative stress and altered gut microbiota in a rodent model of autism.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {65}, number = {1}, pages = {1-7}, pmid = {30782287}, issn = {1165-158X}, mesh = {Animals ; Autistic Disorder/*drug therapy/microbiology ; Bacteria/drug effects/growth &amp; development ; Bees/chemistry ; Clindamycin/*adverse effects ; Colony Count, Microbial ; Cricetinae ; Disease Models, Animal ; Gastrointestinal Microbiome/*drug effects ; Male ; *Oxidative Stress/drug effects ; *Prebiotics ; Probiotics/*pharmacology ; Propionates/*adverse effects ; Propolis/*therapeutic use ; ROC Curve ; }, abstract = {Colonization by toxin-producing bacteria in the gut plays a major role in bowel problems in autistic patients. Prebiotics can inhibit the growth of these pathogenic microbes by nourishing beneficial bacteria, while probiotics--live microorganisms--can balance the gut bacteria; thus, both together can maintain healthy bacteria in the gut. The present study was conducted to find the effect of probiotics and prebiotics in balancing the gut flora in a rodent model of autism linked with a clindamycin-induced altered gut. The effects of probiotics and prebiotics on oxidative stress markers in the brain were also evaluated. Eight groups of hamsters were assigned, with Group I serving as the control; Group II, as the autistic model, was treated with 250 mg propionic acid/kg BW/day for 3 days; Group III was treated with clindamycin 30 mg/kg BW for 3 days; Groups IV and V were treated with bee pollen and propolis (supposed prebiotics) at a dose of 250 mg/kg BW/day for 28 days; Group VI and Group VII were treated with Lactobacillus paracaseii and Protexin® (supposed probiotics) for 28 days; and finally, Group VIII was anorectally transplanted with stool from normal animals for 5 days. Remarkable changes were measured in oxidative stress markers, primarily glutathione and vitamin C, in the brains of hamsters in the propionic acid- and clindamycin-treated group. All probiotic/prebiotic treatments showed ameliorative effects; however, lactobacillus had the strongest effect. We conclude that pro-and prebiotic supplements may be effective to revive healthy digestive system function in autistic patients. The disappointing results of the fecal transplants suggest that further study is needed to develop an appropriate technique.}, }
@article {pmid30782238, year = {2019}, author = {Cai, T and Shi, X and Yuan, LZ and Tang, D and Wang, F}, title = {Fecal microbiota transplantation in an elderly patient with mental depression.}, journal = {International psychogeriatrics}, volume = {31}, number = {10}, pages = {1525-1526}, doi = {10.1017/S1041610219000115}, pmid = {30782238}, issn = {1741-203X}, mesh = {Aged ; Depression/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Mental Health ; Psychiatric Status Rating Scales ; }, }
@article {pmid30778870, year = {2019}, author = {Allegretti, JR and Fischer, M and Sagi, SV and Bohm, ME and Fadda, HM and Ranmal, SR and Budree, S and Basit, AW and Glettig, DL and de la Serna, EL and Gentile, A and Gerardin, Y and Timberlake, S and Sadovsky, R and Smith, M and Kassam, Z}, title = {Correction to: Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Low Dose.}, journal = {Digestive diseases and sciences}, volume = {64}, number = {7}, pages = {2059}, doi = {10.1007/s10620-019-05527-4}, pmid = {30778870}, issn = {1573-2568}, abstract = {The original version of the article unfortunately contained an error in article title. The corrected title is 'Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Low Dose'.}, }
@article {pmid30777557, year = {2019}, author = {Shad, S and Hanif, F and Ul Haq, M and Luck, NH and Aziz, T and Mubarak, M}, title = {Frequencies of Common Infectious Organisms Causing Chronic Diarrhea in Renal Transplant Patients.}, journal = {Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation}, volume = {17}, number = {Suppl 1}, pages = {212-215}, doi = {10.6002/ect.MESOT2018.P69}, pmid = {30777557}, issn = {2146-8427}, mesh = {Adult ; Chronic Disease ; Comorbidity ; Cross-Sectional Studies ; Diarrhea/diagnosis/*epidemiology/immunology ; Feces/microbiology/parasitology ; Female ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/adverse effects ; Kidney Transplantation/*adverse effects ; Male ; Opportunistic Infections/diagnosis/*epidemiology/immunology ; Pakistan/epidemiology ; Prevalence ; Risk Factors ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVES: Gastrointestinal complications are common in kidney transplant patients, with the most frequent being diarrhea (60%). Chronic diarrhea affects the patient's quality of life, causes fatigue and weight loss and malabsorption, increases the number of hospitalizations, increases serum creatinine levels, and causes alterations in immunosuppressive drug levels. Diarrhea is also associated with an increased risk of graft failure and death. In this study, we aimed to determine the frequencies of common infectious organisms causing chronic diarrhea in renal transplant patients.<br><br>MATERIALS AND METHODS: Our study included 124 renal transplant patients who presented with chronic diarrhea over a 6-month period at the Sindh Institute of Urology and Transplantation Department tertiary care hospital (Karachi, Pakistan). Stool analysis was performed in all transplant recipients. Upper and lower gastrointestinal endoscopy was also performed in patients with chronic diarrhea, and biopsy specimens underwent histopathologic evaluations.<br><br>RESULTS: Of 124 renal transplant recipients, 29 were female (23.4%) and 95 were male (76.6%). Giardia was the most common organism found (n = 37 patients; 29.8%) followed by Cryptosporidium (n = 36; 29.0%), Entameba histolytica (n = 29; 23.4%), tuberculosis (n = 14; 11.3%), and sprue (n =8; 6.5%). The mean duration since renal transplant was 78.5 &#xb1; 63.37 months. Although not statistically significant, the frequency of diarrhea was higher in patients who had transplant procedures &#x2265; 2 years previously.<br><br>CONCLUSIONS: Chronic diarrhea is prevalent in renal transplant patients irrespective of age, sex, and duration since transplant. Giardiasis and Cryptosporidium species infections are important causes of chronic diarrhea, but other causative factors need to be further studied, including comorbid conditions and immunosuppressive agents.}, }
@article {pmid30777006, year = {2019}, author = {Schmitt, FCF and Brenner, T and Uhle, F and Loesch, S and Hackert, T and Ulrich, A and Hofer, S and Dalpke, AH and Weigand, MA and Boutin, S}, title = {Gut microbiome patterns correlate with higher postoperative complication rates after pancreatic surgery.}, journal = {BMC microbiology}, volume = {19}, number = {1}, pages = {42}, pmid = {30777006}, issn = {1471-2180}, mesh = {Aged ; Bacteria/*classification/isolation &amp; purification ; Feces/microbiology ; *Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Odds Ratio ; Pancreatic Diseases/*surgery ; Phylogeny ; Pilot Projects ; Postoperative Complications/*microbiology ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; }, abstract = {BACKGROUND: Postoperative complications are of great relevance in daily clinical practice, and the gut microbiome might play an important role by preventing pathogens from crossing the intestinal barrier. The two aims of this prospective clinical pilot study were: (1) to examine changes in the gut microbiome following pancreatic surgery, and (2) to correlate these changes with the postoperative course of the patient.<br><br>RESULTS: In total, 116 stool samples of 32 patients undergoing pancreatic surgery were analysed by 16S-rRNA gene next-generation sequencing. One sample per patient was collected preoperatively in order to determine the baseline gut microbiome without exposure to surgical stress and/or antibiotic use. At least two further samples were obtained within the first 10&#x2009;days following the surgical procedure to observe longitudinal changes in the gut microbiome. Whenever complications occurred, further samples were examined. Based on the structure of the gut microbiome, the samples could be allocated into three different microbial communities (A, B and C). Community B showed an increase in Akkermansia, Enterobacteriaceae and Bacteroidales as well as a decrease in Lachnospiraceae, Prevotella and Bacteroides. Patients showing a microbial composition resembling community B at least once during the observation period were found to have a significantly higher risk for developing postoperative complications (B vs. A, odds ratio&#x2009;=&#x2009;4.96, p&#x2009;<&#x2009;0.01**; B vs. C, odds ratio&#x2009;=&#x2009;2.89, p&#x2009;=&#x2009;0.019*).<br><br>CONCLUSIONS: The structure of the gut microbiome is associated with the development of postoperative complications.}, }
@article {pmid30775438, year = {2019}, author = {Zheng, P and Zeng, B and Liu, M and Chen, J and Pan, J and Han, Y and Liu, Y and Cheng, K and Zhou, C and Wang, H and Zhou, X and Gui, S and Perry, SW and Wong, ML and Licinio, J and Wei, H and Xie, P}, title = {The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice.}, journal = {Science advances}, volume = {5}, number = {2}, pages = {eaau8317}, pmid = {30775438}, issn = {2375-2548}, abstract = {Schizophrenia (SCZ) is a devastating mental disorder with poorly defined underlying molecular mechanisms. The gut microbiome can modulate brain function and behaviors through the microbiota-gut-brain axis. Here, we found that unmedicated and medicated patients with SCZ had a decreased microbiome α-diversity index and marked disturbances of gut microbial composition versus healthy controls (HCs). Several unique bacterial taxa (e.g., Veillonellaceae and Lachnospiraceae) were associated with SCZ severity. A specific microbial panel (Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae) enabled discriminating patients with SCZ from HCs with 0.769 area under the curve. Compared to HCs, germ-free mice receiving SCZ microbiome fecal transplants had lower glutamate and higher glutamine and GABA in the hippocampus and displayed SCZ-relevant behaviors similar to other mouse models of SCZ involving glutamatergic hypofunction. Together, our findings suggest that the SCZ microbiome itself can alter neurochemistry and neurologic function in ways that may be relevant to SCZ pathology.}, }
@article {pmid30772848, year = {2019}, author = {Woodhouse, CA and Patel, VC and Goldenberg, S and Sanchez-Fueyo, A and China, L and O'Brien, A and Flach, C and Douiri, A and Shawcross, D}, title = {PROFIT, a PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis: study protocol for a single-blinded trial.}, journal = {BMJ open}, volume = {9}, number = {2}, pages = {e023518}, pmid = {30772848}, issn = {2044-6055}, support = {MR/L008890/1/MRC_/Medical Research Council/United Kingdom ; PB-PG-0215-36070/DH_/Department of Health/United Kingdom ; }, mesh = {Feasibility Studies ; Fecal Microbiota Transplantation/*methods ; Humans ; Liver Cirrhosis/*therapy ; Prospective Studies ; Randomized Controlled Trials as Topic ; Single-Blind Method ; }, abstract = {INTRODUCTION: Patients with advanced cirrhosis have enteric bacterial dysbiosis and translocation of bacteria and their products across the gut epithelial barrier. This culminates in systemic inflammation and endotoxaemia, inducing innate immune dysfunction which predisposes to infection, and development of complications such as bleeding, sepsis and hepatic encephalopathy. This feasibility study aims to assess the safety of administering faecal microbiota transplantion to patients with cirrhosis and explore the effect of the intervention on their prognosis by achieving restoration of a healthy gut microbiome.<br><br>METHODS AND ANALYSIS: A PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation is a single-centre, randomised, single-blinded, placebo-controlled study evaluating faecal microbiota transplantation (FMT) against placebo. Patients with advanced but stable cirrhosis with a Model for End-Stage Liver Disease score between 10 and 16 will be recruited. Twenty-four patients will be randomised to FMT plus standard of care (as per our institutional practice) and eight patients to placebo in a ratio of 3:1. Patients will be evaluated at baseline before the study intervention is administered and at 7, 30 and 90 days post-intervention to assess safety and adverse events. FMT/placebo will be administered into the jejunum within 7 days of baseline. The primary outcome measure will be safety and feasibility as assessed by recruitment rates, tolerability and safety of FMT treatment. Results will be disseminated via peer-reviewed journals and international conferences. The recruitment of the first patient occurred on 23 May 2018.<br><br>ETHICS AND DISSEMINATION: Research Ethics approval was given by the London South East Research Ethics committee (ref 17/LO/2081).<br><br>TRIAL REGISTRATION NUMBER: NCT02862249 and EudraCT 2017-003629-13.}, }
@article {pmid30771528, year = {2019}, author = {Huttner, BD and Galperine, T and Kapel, N and Harbarth, S}, title = {'A five-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae' - Author's reply.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {25}, number = {7}, pages = {914-915}, doi = {10.1016/j.cmi.2019.02.001}, pmid = {30771528}, issn = {1469-0691}, mesh = {Anti-Bacterial Agents ; *Enterobacteriaceae ; *Enterobacteriaceae Infections ; Fecal Microbiota Transplantation ; Humans ; beta-Lactamases ; }, }
@article {pmid30770201, year = {2019}, author = {Farowski, F and Solbach, P and Tsakmaklis, A and Brodesser, S and Cruz Aguilar, MR and Cornely, OA and Dettmer, K and Higgins, PG and Suerbaum, S and Jazmati, N and Oefner, PJ and Vehreschild, MJGT and , }, title = {Potential biomarkers to predict outcome of faecal microbiota transfer for recurrent Clostridioides difficile infection.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {51}, number = {7}, pages = {944-951}, doi = {10.1016/j.dld.2019.01.012}, pmid = {30770201}, issn = {1878-3562}, mesh = {Aged ; Aged, 80 and over ; Biomarkers/metabolism ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/chemistry ; Female ; *Gastrointestinal Microbiome ; Humans ; Lithocholic Acid/*metabolism ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Faecal microbiota transplantation (FMT) has proven high clinical efficacy in the management of recurrent Clostridioides difficile infection (rCDI) with cure rates of over 80% after a single treatment. Nevertheless, the reasons for failure in the remaining 20% remain elusive. The aim of the present study was to investigate different potential predictors of response to FMT.<br><br>METHODS: Faecal specimens of sixteen patients undergoing FMT for rCDI, as well as samples from the respective donors were collected and analyzed by 16S rRNA gene profiling, bile acid-inducible (baiCD) gene specific qPCR, and liquid chromatography tandem-mass spectrometry (LC-MS/MS) to quantify the concentrations of primary and secondary bile acids.<br><br>RESULTS: Using the faecal concentration of the secondary bile acid lithocholic acid (LCA)within the patient specimens, we were able to predict response to FMT (accuracy 95.2%, sensitivity 100%, specificity 90.9%). By combining the faecal LCA concentration with the urinary pCS concentration, an accuracy of 100% was achieved.<br><br>CONCLUSION: LCA appears to be a promising marker candidate for prediction of clinical response to FMT. Other makers, such as urinary concentration of pCS, but not 3-IS, might be used to improve accuracy of prediction. Further studies are warranted to validate these candidate markers.}, }
@article {pmid30763538, year = {2019}, author = {Gogokhia, L and Buhrke, K and Bell, R and Hoffman, B and Brown, DG and Hanke-Gogokhia, C and Ajami, NJ and Wong, MC and Ghazaryan, A and Valentine, JF and Porter, N and Martens, E and O'Connell, R and Jacob, V and Scherl, E and Crawford, C and Stephens, WZ and Casjens, SR and Longman, RS and Round, JL}, title = {Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis.}, journal = {Cell host &amp; microbe}, volume = {25}, number = {2}, pages = {285-299.e8}, pmid = {30763538}, issn = {1934-6069}, support = {DP2 AT008746/AT/NCCIH NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; R00 HL102228/HL/NHLBI NIH HHS/United States ; T32 HG008962/HG/NHGRI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R01 DK114252/DK/NIDDK NIH HHS/United States ; DP2 GM111099/GM/NIGMS NIH HHS/United States ; N01AI95375/AI/NIAID NIH HHS/United States ; T32 GM145304/GM/NIGMS NIH HHS/United States ; R01 GM114817/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*virology ; *Bacteriophages ; CD4-Positive T-Lymphocytes/metabolism ; Colitis, Ulcerative/*immunology/*microbiology/pathology ; Colorectal Neoplasms/*immunology/*microbiology/pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Interferon-gamma/metabolism ; Intestinal Mucosa/*immunology/*microbiology/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pilot Projects ; Prospective Studies ; Specific Pathogen-Free Organisms ; }, abstract = {Bacteriophages are the most abundant members of the microbiota and have the potential to shape gut bacterial communities. Changes to bacteriophage composition are associated with disease, but how phages impact mammalian health remains unclear. We noted an induction of host immunity when experimentally treating bacterially driven cancer, leading us to test whether bacteriophages alter immune responses. Treating germ-free mice with bacteriophages leads to immune cell expansion in the gut. Lactobacillus, Escherichia, and Bacteroides bacteriophages and phage DNA stimulated IFN-γ via the nucleotide-sensing receptor TLR9. The resultant immune responses were both phage and bacteria specific. Additionally, increasing bacteriophage levels exacerbated colitis via TLR9 and IFN-γ. Similarly, ulcerative colitis (UC) patients responsive to fecal microbiota transplantation (FMT) have reduced phages compared to non-responders, and mucosal IFN-γ positively correlates with bacteriophage levels. Bacteriophages from active UC patients induced more IFN-γ compared to healthy individuals. Collectively, these results indicate that bacteriophages can alter mucosal immunity to impact mammalian health.}, }
@article {pmid30762209, year = {2019}, author = {Oneto, C and Feuerstadt, P}, title = {Concise Commentary: Treatment of Recurrent C. difficile Infection: A New Take on the Fecal-Oral Route.}, journal = {Digestive diseases and sciences}, volume = {64}, number = {6}, pages = {1679}, pmid = {30762209}, issn = {1573-2568}, mesh = {Capsules ; *Clostridioides difficile ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid30761273, year = {2019}, author = {Li, X and Song, L and Zhu, S and Xiao, Y and Huang, Y and Hua, Y and Chu, Q and Ren, Z}, title = {Two Strains of Lactobacilli Effectively Decrease the Colonization of VRE in a Mouse Model.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {6}, pmid = {30761273}, issn = {2235-2988}, mesh = {Animals ; *Antibiosis ; Carrier State/*therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Tract/*microbiology ; Gram-Positive Bacterial Infections/*therapy ; Lactobacillus/*growth &amp; development ; Mice ; Treatment Outcome ; Vancomycin-Resistant Enterococci/*growth &amp; development ; }, abstract = {Vancomycin-resistant Enterococcus (VRE) infection is a serious challenge for clinical management and there is no effective treatment at present. Fecal microbiota transplantation (FMT) and probiotic intervention have been shown to be promising approaches for reducing the colonization of certain pathogenic bacteria in the gastrointestinal tract, however, no such studies have been done on VRE. In this study, we evaluated the effect of FMT and two Lactobacillus strains (Y74 and HT121) on the colonization of VRE in a VRE-infection mouse model. We found that both Lactobacilli strains reduced VRE colonization rapidly. Fecal microbiota and colon mRNA expression analyses further showed that mice in FMT and the two Lactobacilli treatment groups restored their intestinal microbiota diversity faster than those in the phosphate buffer saline (PBS) treated group. Administration of Lactobacilli restored Firmicutes more quickly to the normal level, compared to FMT or PBS treatment, but restored Bacteroides to their normal level less quickly than FMT did. Furthermore, these treatments also had an impact on the relative abundance of intestinal microbiota composition from phylum to species level. RNA-seq showed that FMT treatment induced the expression of more genes in the colon, compared to the Lactobacilli treatment. Defense-related genes such as defensin α, Apoa1, and RegIII were down-regulated in both FMT and the two Lactobacilli treatment groups. Taken together, our findings indicate that both FMT and Lactobacilli treatments were effective in decreasing the colonization of VRE in the gut.}, }
@article {pmid30761129, year = {2019}, author = {Heimesaat, MM and Escher, U and Grunau, A and Kühl, AA and Bereswill, S}, title = {Multidrug-Resistant Pseudomonas aeruginosa Accelerate Intestinal, Extra-Intestinal, and Systemic Inflammatory Responses in Human Microbiota-Associated Mice With Subacute Ileitis.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {49}, pmid = {30761129}, issn = {1664-3224}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Apoptosis ; Bacterial Load ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects ; Host-Pathogen Interactions ; Humans ; Ileitis/*diagnosis/drug therapy/*etiology ; Intestinal Mucosa/immunology/microbiology/pathology ; Mice ; *Microbiota ; Pseudomonas aeruginosa/*drug effects/*physiology ; Systemic Inflammatory Response Syndrome/*diagnosis/drug therapy/*etiology ; }, abstract = {The globally rising incidences of multidrug-resistant (MDR) Pseudomonas aeruginosa (Psae) in humans and live-stock animals has prompted the World Health Organization to rate MDR Psae as serious threat for human health. Only little is known, however, regarding factors facilitating gastrointestinal Psae-acquisition by the vertebrate host and subsequently induced inflammatory sequelae. In the present study, we addressed whether subacute ileitis predisposed mice harboring a human gut microbiota for intestinal MDR Psae carriage and whether inflammatory responses might be induced following peroral challenge with the opportunistic pathogen. To accomplish this, secondary abiotic mice were associated with a human gut microbiota by fecal microbiota transplantation. Ten days later (i.e., on day 0), subacute ileitis was induced in human microbiota associated (hma) mice by peroral low-dose Toxoplasma gondii infection. On day 5 post-infection, mice were perorally challenged with 10[9] colony forming units of a clinical MDR Psae isolate by gavage and the fecal bacterial loads surveyed thereafter. Four days post-peroral challenge, only approximately one third of mice with a human gut microbiota and subacute ileitis harbored the opportunistic pathogen in the intestinal tract. Notably, the gut microbiota composition was virtually unaffected by the Psae-carriage status during subacute ileitis of hma mice. The Psae challenge resulted, however, in more pronounced intestinal epithelial apoptotic cell and T lymphocyte responses upon ileitis induction that were not restricted to the ileum, but also affected the large intestines. Higher Psae-induced abundances of T cells could additionally be observed in extra-intestinal compartments including liver, kidney, lung, and heart of hma mice with subacute ileitis. Furthermore, higher apoptotic cell numbers, but lower anti-inflammatory IL-10 concentrations were assessed in the liver of Psae as compared to mock treated mice with ileitis. Remarkably, Psae-challenge was accompanied by even more pronounced systemic secretion of pro-inflammatory cytokines such as TNF and IL-6 at day 9 post ileitis induction. In conclusion, whereas in one third of hma mice with subacute ileitis Psae could be isolated from the intestines upon peroral challenge, the opportunistic pathogen was responsible for inflammatory sequelae in intestinal, extra-intestinal, and even systemic compartments and thus worsened subacute ileitis outcome irrespective of the Psae-carrier status.}, }
@article {pmid30754077, year = {2019}, author = {Costello, SP and Bryant, RV}, title = {Faecal microbiota transplantation in Australia: bogged down in regulatory uncertainty.}, journal = {Internal medicine journal}, volume = {49}, number = {2}, pages = {148-151}, doi = {10.1111/imj.14212}, pmid = {30754077}, issn = {1445-5994}, mesh = {Australia ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; *Legislation, Medical ; Uncertainty ; }, }
@article {pmid30747433, year = {2018}, author = {Polívková, S and Vojtilová, L and Husa, P and Beneš, J}, title = {[Guideline for fecal bacteriotherapy to treat recurrent Clostridium difficile colitis].}, journal = {Klinicka mikrobiologie a infekcni lekarstvi}, volume = {24}, number = {2}, pages = {57-64}, pmid = {30747433}, issn = {1211-264X}, mesh = {Adolescent ; Anti-N-Methyl-D-Aspartate Receptor Encephalitis/*complications ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Yellow Fever Vaccine/*adverse effects/*immunology ; }, abstract = {We present a case of a 17-year-old female with anti-NMDAR encephalitis probably associated with vaccination against yellow fever. Her symptoms occurred 27 days after vaccination against yellow fever. Anti-NMDAR encephalitis manifested as acute psychosis, memory loss and catatonia following fever with complex partial epileptic seizures. Interictal electroencephalogram showed slow-wave delta background activity with "delta brushes". The diagnosis was confirmed by NMDAR antibody positivity in serum and cerebrospinal fluid. Since ovarian teratoma, as the most common cause of anti-NMDAR encephalitis, did not develop within five years from its onset, the association with vaccination against yellow fever seems to be highly probable.}, }
@article {pmid30738489, year = {2019}, author = {Qi, L and Li, F}, title = {[Current Advances in the Fecal Microbiota Transplantation and Its Application in the Hematologic Diseases--Review].}, journal = {Zhongguo shi yan xue ye xue za zhi}, volume = {27}, number = {1}, pages = {306-310}, doi = {10.7534/j.issn.1009-2137.2019.01.051}, pmid = {30738489}, issn = {1009-2137}, mesh = {Clostridioides difficile ; Clostridium Infections ; Dysbiosis ; Fecal Microbiota Transplantation ; *Hematologic Diseases ; Humans ; Treatment Outcome ; }, abstract = {Intestinal microbiome closely relates with human health and disease, which plays a critical role in the immune response, homeostasis, drug metabolism and tumorigenesis. Imbalances in the composition and function of these intestinal microbes associate with diseases. Fecal microbiota transplantation (FMT) is an established successful treatment modality for recurrent Clostridium difficile infection (CDI). The safety profile and potential therapeutic advantages of FMT for diseases associated with dysbiosis and immune dysfunction have led to many publications, mainly case series. The literature on the use of FMT for hematologic diseases is very limited, however, immune thrombocytopenic purpura（ITP）, CDI and aGVHD after HSCT were reported to be improved by FMT. The aim of this review is to briefly summarize the research current state, procedures and clinical application of FMT.}, }
@article {pmid30738477, year = {2019}, author = {Chen, XY and Wang, SQ}, title = {[Relationship Between the Change of Microbial Diversity and Gastrointestinal Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation].}, journal = {Zhongguo shi yan xue ye xue za zhi}, volume = {27}, number = {1}, pages = {239-245}, doi = {10.7534/j.issn.1009-2137.2019.01.039}, pmid = {30738477}, issn = {1009-2137}, mesh = {*Gastrointestinal Tract ; *Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation ; Humans ; RNA, Ribosomal, 16S ; }, abstract = {OBJECTIVE: To investigate the change of microbial diversity and its relation with gastrointestinal (GI) graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).<br><br>METHODS: Fecal samples were collected at the time point of 2 weeks before transplantation (pre-transplant group), 1 month after transplantation (post-tranplant group) and onset of GI GVHD in 65 hematonosis patients, which were also collected in 26 donors and 10 healthy subjects (control group). 16S rRNA was extracted from fecal microbiotas whose V4 variable region was amplified. The amplification products were sequenced in Illumina HiSeq 2500 platform, and the sequencing results were analyzed and compared.<br><br>RESULTS: The microbial diversity was 5.70&#xff08;3.74, 10.60&#xff09;in pre-transplant group, 7.30&#xff08;4.89, 11.41&#xff09;in control group, and the differences between them were not statistically significant. The microbial diversity was 3.88&#xff08;2.39, 6.49&#xff09;in post-transplant group, lower than that in control group and pre-transplant group. After transplantation, the microbial diversity was 4.24&#xff08;2.47, 7.16&#xff09;in the patients without GI GVHD, while the microbial diverosity was 2.90 (1.48, 5.64) in patients subsequently suffered from GI GVHD, but the differences between them were not statistically significant. The microbial diversity was 2.13&#xff08;1.76, 3.75&#xff09;onset of GI GVHD, which was lower than that without GI GVHD.<br><br>CONCLUSION: Intestinal microbial diversity decreases after allo-HSCT, and is associated with with Gl GVHD.}, }
@article {pmid30733264, year = {2019}, author = {Battipaglia, G and Malard, F and Rubio, MT and Ruggeri, A and Mamez, AC and Brissot, E and Giannotti, F and Dulery, R and Joly, AC and Baylatry, MT and Kossmann, MJ and Tankovic, J and Beaugerie, L and Sokol, H and Mohty, M}, title = {Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematologic malignancies carrying multidrug-resistance bacteria.}, journal = {Haematologica}, volume = {104}, number = {8}, pages = {1682-1688}, pmid = {30733264}, issn = {1592-8721}, mesh = {Adult ; Aged ; *Drug Resistance, Multiple, Bacterial ; Dysbiosis/*etiology/*therapy ; *Fecal Microbiota Transplantation/methods ; Female ; Hematologic Neoplasms/*complications/diagnosis/therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; *Perioperative Care/methods ; Retrospective Studies ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation is an effective treatment in recurrent Clostridium difficile infection. Promising results to eradicate multidrug-resistant bacteria have also been reported with this procedure, but there are safety concerns in immunocompromised patients. We report results in ten adult patients colonized with multidrug-resistant bacteria, undergoing fecal microbiota transplantation before (n=4) or after (n=6) allogeneic hematopoietic stem cell transplantation for hematologic malignancies. were obtained from healthy related or unrelated donors. Fecal material was delivered either by enema or via nasogastric tube. Patients were colonized or had infections from either carbapenemase-producing bacteria (n=8) or vancomycin-resistant enterococci (n=2). Median age at fecal microbiota transplantation was 48 (range, 16-64) years. Three patients needed a second transplant from the same donor due to initial failure of the procedure. With a median follow up of 13 (range, 4-40) months, decolonization was achieved in seven of ten patients. In all patients, fecal micro-biota transplantation was safe: one patient presented with constipation during the first five days after FMT and two patients had grade I diarrhea. One case of gut grade III acute graft-versus-host disease occurred after fecal microbiota transplantation. In patients carrying or infected by multidrug-resistant bacteria, fecal microbiota transplantation is an effective and safe decolonization strategy, even in those with hematologic malignancies undergoing hematopoietic stem cell transplantation.}, }
@article {pmid30731251, year = {2019}, author = {Bekker, V and Zwittink, RD and Knetsch, CW and Sanders, IMJG and Berghuis, D and Heidt, PJ and Vossen, JMJJ and de Vos, WM and Belzer, C and Bredius, RGM and Van't Hof, PJ and Lankester, AC and Kuijper, EJ}, title = {Dynamics of the Gut Microbiota in Children Receiving Selective or Total Gut Decontamination Treatment during Hematopoietic Stem Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {25}, number = {6}, pages = {1164-1171}, doi = {10.1016/j.bbmt.2019.01.037}, pmid = {30731251}, issn = {1523-6536}, mesh = {Adolescent ; Child ; Child, Preschool ; Decontamination ; Female ; Gastrointestinal Microbiome/*drug effects ; Hematopoietic Stem Cell Transplantation/*methods ; Humans ; Male ; Microbiota/*drug effects ; Prospective Studies ; Transplantation Conditioning/*methods ; }, abstract = {Bloodstream infections and graft-versus-host disease are common complications after hematopoietic stem cell transplantation (HSCT) procedures, associated with the gut microbiota that acts as a reservoir for opportunistic pathogens. Selective gut decontamination (SGD) and total gut decontamination (TGD) during HSCT have been associated with a decreased risk of developing these complications after transplantation. However, because studies have shown conflicting results, the use of these treatments remains subject of debate. In addition, their impact on the gut microbiota is not well studied. The aim of this study was to elucidate the dynamics of the microbiota during and after TGD and to compare these with the dynamics of SGD. In this prospective, observational, single-center study fecal samples were longitudinally collected from 19 children eligible for allogenic HSCT (TGD, n=12; SGD, n=7), weekly during hospital admission and monthly after discharge. In addition, fecal samples were collected from 3 family stem cell donors. Fecal microbiota structure of patients and donors was determined by 16S rRNA gene amplicon sequencing. Microbiota richness and diversity markedly decreased during SGD and TGD and gradually increased after cessation of decontamination treatment. During SGD, gut microbiota composition was relatively stable and dominated by Bacteroides, whereas it showed high inter- and intraindividual variation and low Bacteroides abundance during TGD. In some children TGD allowed the genera Enterococcus and Streptococcus to thrive during treatment. A gut microbiota dominated by Bacteroides was associated with increased predicted activity of several metabolic processes. Comparing the microbiota of recipients and their donors indicated that receiving an SCT did not alter the patient's microbiota to become more similar to that of its donor. Overall, our findings indicate that SGD and TGD affect gut microbiota structure in a treatment-specific manner. Whether these treatments affect clinical outcomes via interference with the gut microbiota needs to be further elucidated.}, }
@article {pmid30730351, year = {2019}, author = {Allegretti, JR and Kassam, Z and Carrellas, M and Mullish, BH and Marchesi, JR and Pechlivanis, A and Smith, M and Gerardin, Y and Timberlake, S and Pratt, DS and Korzenik, JR}, title = {Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: A Pilot Clinical Trial.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {7}, pages = {1071-1079}, doi = {10.14309/ajg.0000000000000115}, pmid = {30730351}, issn = {1572-0241}, support = {MC_PC_17162/MRC_/Medical Research Council/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Boston ; Cholangitis, Sclerosing/diagnosis/immunology/*therapy ; Colonoscopy/methods ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Gastrointestinal Microbiome/*immunology ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; *Patient Safety ; Pilot Projects ; Prognosis ; Regression Analysis ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed at evaluating the safety, change in liver enzymes, microbiota, and metabolomic profiles in patients with PSC after FMT.<br><br>METHODS: An open-label pilot study of patients with PSC with concurrent inflammatory bowel disease and alkaline phosphatase (ALP) > 1.5&#xd7; the upper limit of normal was conducted. The patients underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis were conducted at baseline and weeks 1, 4, 8, 12, and 24 post-FMT. The primary outcome was safety, and the secondary outcome was a decrease in ALP levels &#x2265;50% from baseline by week 24 post-FMT; stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed.<br><br>RESULTS: Ten patients underwent FMT. Nine patients had ulcerative colitis, and 1 had Crohn's colitis. The mean baseline ALP level was 489 U/L. There were no related adverse events. Overall, 30% (3/10) experienced a &#x2265;50% decrease in ALP levels. The diversity increased in all patients post-FMT, as early as week 1 (P < 0.01). Importantly, abundance of engrafter operational taxonomic units in patients post-FMT correlated with decreased ALP levels (P = 0.02).<br><br>DISCUSSION: To our knowledge, this is the first study to demonstrate that FMT in PSC is safe. In addition, increases in bacterial diversity and engraftment may correlate with an improvement in ALP among patients with PSC.}, }
@article {pmid30728535, year = {2019}, author = {Chakradhar, S}, title = {Positive selection.}, journal = {Nature medicine}, volume = {25}, number = {2}, pages = {192-194}, doi = {10.1038/s41591-019-0351-4}, pmid = {30728535}, issn = {1546-170X}, mesh = {Bacteria/isolation &amp; purification/*metabolism ; Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Probiotics/pharmacology ; }, }
@article {pmid30725005, year = {2018}, author = {Cruz, R and Monrroy, H and Flandez, J and Pérez, CM and Álvarez-Lobos, M and Hernández-Rocha, C}, title = {[Practical clues for a fecal microbiota transplantation by colonoscopy for recurrent Clostridium difficile infection. Experience in a University center].}, journal = {Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia}, volume = {35}, number = {5}, pages = {566-573}, doi = {10.4067/s0716-10182018000500566}, pmid = {30725005}, issn = {0717-6341}, mesh = {Adult ; Aged ; Clostridium Infections/*therapy ; Colonoscopy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is a highly effective therapy in recurrent Clostridium difficile. The best route to administrate the fecal matter has not been established yet. However, the lower gastrointestinal route by colonoscopy is effective and safe, presenting a higher acceptance by patients. In addition, this route allows an evaluation of colonic mucosa seeking for differential diagnostics. We present a case series of FMT performed in our institution by colonoscopy, highlighting outcomes and practical aspects for its implementation.}, }
@article {pmid30721960, year = {2019}, author = {Cuevas-Sierra, A and Ramos-Lopez, O and Riezu-Boj, JI and Milagro, FI and Martinez, JA}, title = {Diet, Gut Microbiota, and Obesity: Links with Host Genetics and Epigenetics and Potential Applications.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {10}, number = {suppl_1}, pages = {S17-S30}, pmid = {30721960}, issn = {2156-5376}, mesh = {Animals ; DNA Methylation ; *Diet ; Dysbiosis/*complications ; Energy Metabolism ; *Epigenesis, Genetic ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Membrane Proteins/metabolism ; MicroRNAs ; Obesity/etiology/genetics/microbiology/*prevention &amp; control ; Prebiotics ; Precision Medicine ; Probiotics ; }, abstract = {Diverse evidence suggests that the gut microbiota is involved in the development of obesity and associated comorbidities. It has been reported that the composition of the gut microbiota differs in obese and lean subjects, suggesting that microbiota dysbiosis can contribute to changes in body weight. However, the mechanisms by which the gut microbiota participates in energy homeostasis are unclear. Gut microbiota can be modulated positively or negatively by different lifestyle and dietary factors. Interestingly, complex interactions between genetic background, gut microbiota, and diet have also been reported concerning the risk of developing obesity and metabolic syndrome features. Moreover, microbial metabolites can induce epigenetic modifications (i.e., changes in DNA methylation and micro-RNA expression), with potential implications for health status and susceptibility to obesity. Also, microbial products, such as short-chain fatty acids or membrane proteins, may affect host metabolism by regulating appetite, lipogenesis, gluconeogenesis, inflammation, and other functions. Metabolomic approaches are being used to identify new postbiotics with biological activity in the host, allowing discovery of new targets and tools for incorporation into personalized therapies. This review summarizes the current understanding of the relations between the human gut microbiota and the onset and development of obesity. These scientific insights are paving the way to understanding the complex relation between obesity and microbiota. Among novel approaches, prebiotics, probiotics, postbiotics, and fecal microbiome transplantation could be useful to restore gut dysbiosis.}, }
@article {pmid30719428, year = {2019}, author = {Wilson, BC and Vatanen, T and Cutfield, WS and O'Sullivan, JM}, title = {The Super-Donor Phenomenon in Fecal Microbiota Transplantation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {2}, pmid = {30719428}, issn = {2235-2988}, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Tissue Donors ; }, abstract = {Fecal microbiota transplantation (FMT) has become a highly effective bacteriotherapy for recurrent Clostridium difficile infection. Meanwhile the efficacy of FMT for treating chronic diseases associated with microbial dysbiosis has so far been modest with a much higher variability in patient response. Notably, a number of studies suggest that FMT success is dependent on the microbial diversity and composition of the stool donor, leading to the proposition of the existence of FMT super-donors. The identification and subsequent characterization of super-donor gut microbiomes will inevitably advance our understanding of the microbial component of chronic diseases and allow for more targeted bacteriotherapy approaches in the future. Here, we review the evidence for super-donors in FMT and explore the concept of keystone species as predictors of FMT success. Possible effects of host-genetics and diet on FMT engraftment and maintenance are also considered. Finally, we discuss the potential long-term applicability of FMT for chronic disease and highlight how super-donors could provide the basis for dysbiosis-matched FMTs.}, }
@article {pmid30719359, year = {2019}, author = {Harsch, IA and Konturek, PC}, title = {Adhesion Ileus after Fecal Microbiota Transplantation in Long-Standing Radiation Colitis.}, journal = {Case reports in gastrointestinal medicine}, volume = {2019}, number = {}, pages = {2543808}, pmid = {30719359}, issn = {2090-6528}, abstract = {Fecal microbiota transplantation (FMT) is a novel strategy for the therapy of dysbiosis-associated disorders via modulation of the gut microbiota. Intestinal dysbiosis is associated not only with digestive disorders, but also with a variety of extra-digestive disorders. A worldwide increasing number of FMT can be expected in the future as well as an increase in adverse events. We describe the case of a patient with chronic radiation colitis that developed adhesion ileus 2 days after FMT. Since these problems never occured before and the short time interval favours a causality, we speculate about FMT-induced alterations in gut motility causing a "trapping" of the small intestine in an adhesion and other mechanisms beyond "pure" coincidence.}, }
@article {pmid30715301, year = {2019}, author = {Ma, D and Chen, Y and Chen, T}, title = {Vaginal microbiota transplantation for the treatment of bacterial vaginosis: a conceptual analysis.}, journal = {FEMS microbiology letters}, volume = {366}, number = {4}, pages = {}, doi = {10.1093/femsle/fnz025}, pmid = {30715301}, issn = {1574-6968}, mesh = {Female ; Humans ; Microbiota/*physiology ; Transplantation ; Vagina/*microbiology ; Vaginosis, Bacterial/*microbiology/*therapy ; }, abstract = {Bacterial vaginosis (BV), caused by the vaginal dysbacteriosis as well as the excessive growth of pathogenic bacteria, is a pathological condition of the vagina; its treatment using the antibiotics metronidazole or clindamycin often causes high recurrence rates. Considering the similar physiological environments of the intestinal tract and vaginal tract, as well as the pathological mechanism of intestinal infection and vaginal infection, we first propose the conception of vaginal microbiota transplantation (VMT) and discuss its potential use in BV. This review focuses on the pathology of BV and the side effects caused by its standardised treatment. The extremely dynamic and diverse gut microbiota forms the most intensive microbial system and also plays a significant role in human body, and Lactobacilli dominate in the vaginal tract of women, keeping them healthy. Accordingly, we also propose the concept of VMT based on the effects of faecal microbiota transplantation (FMT) in treating intestinal infections, and list the potential hurdles for the implementation of VMT.}, }
@article {pmid30710103, year = {2019}, author = {York, A}, title = {FMT in the clinic.}, journal = {Nature reviews. Microbiology}, volume = {17}, number = {3}, pages = {127}, doi = {10.1038/s41579-019-0157-x}, pmid = {30710103}, issn = {1740-1534}, mesh = {*Biodiversity ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, }
@article {pmid30709065, year = {2019}, author = {Evrensel, A and Önen Ünsalver, B and Ceylan, ME}, title = {Therapeutic Potential of the Microbiome in the Treatment of Neuropsychiatric Disorders.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {7}, number = {2}, pages = {}, pmid = {30709065}, issn = {2076-3271}, abstract = {The search for rational treatment of neuropsychiatric disorders began with the discovery of chlorpromazine in 1951 and continues to evolve. Day by day, new details of the intestinal microbiota[-]brain axis are coming to light. As the role of microbiota in the etiopathogenesis of neuropsychiatric disorders is more clearly understood, microbiota-based (or as we propose, "fecomodulation") treatment options are increasingly discussed in the context of treatment. Although their history dates back to ancient times, the importance of psychobiotics and fecal microbiota transplantation (FMT) has only recently been recognized. Despite there being few preclinical and clinical studies, the evidence gathered to this point suggests that consideration of the microbiome in the treatment of neuropsychiatric disorders represents an area of significant therapeutic potential. It is increasingly hoped that such treatment options will be more reliable in terms of their side effects, cost, and ease of implementation. However, there remains much to be researched. Questions will be answered through germ-free animal experiments and randomized controlled trials. In this article, the therapeutic potential of microbiota-based options in the treatment of neuropsychiatric disorders is discussed in light of recent research.}, }
@article {pmid30708122, year = {2019}, author = {Tacconelli, E and Mazzaferri, F and de Smet, AM and Bragantini, D and Eggimann, P and Huttner, BD and Kuijper, EJ and Lucet, JC and Mutters, NT and Sanguinetti, M and Schwaber, MJ and Souli, M and Torre-Cisneros, J and Price, JR and Rodríguez-Baño, J}, title = {ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {25}, number = {7}, pages = {807-817}, doi = {10.1016/j.cmi.2019.01.005}, pmid = {30708122}, issn = {1469-0691}, mesh = {Acinetobacter baumannii/drug effects ; Anti-Bacterial Agents/*pharmacology ; Cross Infection/drug therapy ; *Drug Resistance, Multiple, Bacterial ; Europe ; Gram-Negative Bacteria/*drug effects ; Gram-Negative Bacterial Infections/*drug therapy ; Humans ; Immunocompromised Host ; Pseudomonas aeruginosa/drug effects ; Stenotrophomonas maltophilia/drug effects ; }, abstract = {SCOPE: The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings.<br><br>METHODS: These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations.<br><br>RECOMMENDATIONS: The panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints.}, }
@article {pmid30707717, year = {2019}, author = {Stadlbauer, V and Horvath, A and Komarova, I and Schmerboeck, B and Feldbacher, N and Wurm, S and Klymiuk, I and Durdevic, M and Rainer, F and Blesl, A and Stryeck, S and Madl, T and Stiegler, P and Leber, B}, title = {A single alcohol binge impacts on neutrophil function without changes in gut barrier function and gut microbiome composition in healthy volunteers.}, journal = {PloS one}, volume = {14}, number = {2}, pages = {e0211703}, pmid = {30707717}, issn = {1932-6203}, support = {I 3792/FWF_/Austrian Science Fund FWF/Austria ; P 28854/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Adult ; Binge Drinking/*complications/*immunology ; Cohort Studies ; Ethanol/metabolism ; Feces/microbiology ; Gastric Mucosa/drug effects ; Gastrointestinal Microbiome/drug effects/genetics ; Healthy Volunteers ; Humans ; Inflammation/complications ; Neutrophils/*drug effects ; RNA, Ribosomal, 16S/analysis ; Young Adult ; }, abstract = {Alcohol binge drinking is a dangerous drinking habit, associated with neurological problems and inflammation. The impact of a single alcohol binge on innate immunity, gut barrier and gut microbiome was studied. In this cohort study 15 healthy volunteers received 2 ml vodka 40% v/v ethanol/kg body weight. Neutrophil function was studied by flow cytometry; markers of gut permeability and inflammation (lactulose/mannitol/sucrose test, zonulin, calprotectin, diamino-oxidase) were studied with NMR spectroscopy and enzyme-linked immunosorbent assay in urine, stool and serum respectively. Bacterial products in serum were quantified using different reporter cell lines. Gut microbiome composition was studied by 16S rDNA sequencing and bioinformatics analysis. After a single alcohol binge, neutrophils were transiently primed and the response to E.coli stimulation with reactive oxygen species (ROS) production was transiently increased, on the other hand the percentage of neutrophils that did not perform phagocytosis increased. No changes in gut permeability, inflammatory biomarker, bacterial translocation and microbiome composition could be detected up to 4 hours after a single alcohol binge or on the next day. A single alcohol binge in young, healthy volunteers transiently impacts on neutrophil function. Although the exact biological consequence of this finding is not clear yet, we believe that this strengthens the importance to avoid any alcohol binge drinking, even in young, otherwise healthy persons.}, }
@article {pmid30705252, year = {2019}, author = {Yang, C and Fang, X and Zhan, G and Huang, N and Li, S and Bi, J and Jiang, R and Yang, L and Miao, L and Zhu, B and Luo, A and Hashimoto, K}, title = {Key role of gut microbiota in anhedonia-like phenotype in rodents with neuropathic pain.}, journal = {Translational psychiatry}, volume = {9}, number = {1}, pages = {57}, pmid = {30705252}, issn = {2158-3188}, mesh = {Anhedonia/*physiology ; Animals ; Behavior, Animal ; Depression/complications/*microbiology ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Male ; Mice, Inbred C57BL ; Neuralgia/complications/*microbiology/*psychology ; Phenotype ; Rats, Sprague-Dawley ; Sciatic Nerve/injuries ; }, abstract = {Patients with chronic neuropathic pain frequently suffer from symptoms of anhedonia, which is a core symptom of depression. Accumulating studies suggest that gut microbiota may play a role in depression via gut-microbiota-brain axis. However, it is unknown whether gut microbiota plays a role in neuropathic pain-associated anhedonia. Here, we used a rat model of spared nerve injury (SNI). Hierarchical cluster analysis of sucrose preference test (SPT) results was used to classify the SNI rats with or without anhedonia-like phenotype. The 16S ribosomal RNA sequencing analysis showed abnormal composition of gut microbiota in the anhedonia susceptible compared to sham-operated rats and resilient rats. Furthermore, antibiotics-treated mice showed pain as well as depression-like and anhedonia-like phenotypes, suggesting a role of gut microbiota in these abnormal behaviors. Transplantation of fecal microbiota from anhedonia susceptible rats into antibiotics-treated pseudo-germ-free mice significantly exaggerated pain and depression-like phenotypes, including anhedonia. In contrast, transplantation of fecal microbiota from resilient rats into antibiotics-treated pseudo-germ-free mice significantly improved pain and depression-like phenotypes, including anhedonia. In conclusion, this study suggests that abnormal composition of gut microbiota may contribute to anhedonia susceptibility post SNI surgery, and that gut microbiota also plays a role in the pain as well as depression-like phenotypes. Interestingly, fecal microbiota transplantation from SNI rats with or without anhedonia can alter pain, depression-like and anhedonia-like phenotypes in the pseudo-germ-free mice. Therefore, it is likely that gut microbiota plays a key role in the pain as well as depression-like phenotypes including anhedonia in rodents with neuropathic pain.}, }
@article {pmid30704621, year = {2019}, author = {Sun, SS and Wang, K and Ma, K and Bao, L and Liu, HW}, title = {An insoluble polysaccharide from the sclerotium of Poria cocos improves hyperglycemia, hyperlipidemia and hepatic steatosis in ob/ob mice via modulation of gut microbiota.}, journal = {Chinese journal of natural medicines}, volume = {17}, number = {1}, pages = {3-14}, doi = {10.1016/S1875-5364(19)30003-2}, pmid = {30704621}, issn = {1875-5364}, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Butyrates/metabolism ; Fatty Liver/drug therapy ; Fungal Polysaccharides/chemistry/*pharmacology/*therapeutic use ; Gastrointestinal Microbiome/*drug effects/genetics ; Hyperglycemia/drug therapy ; Hyperlipidemias/drug therapy ; Intestines/drug effects/microbiology ; Male ; Metabolic Syndrome/*drug therapy ; Mice ; Mice, Obese ; Prebiotics ; Wolfiporia/*chemistry ; }, abstract = {Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide (WIP) was isolated and identified from the sclerotium of Poria cocos, a widely used Traditional Chinese Medicine. WIP was confirmed to be a (1-3)-β-D-glucan with an average Mw of 4.486 × 10[6] Da by NMR and SEC-RI-MALLS analyses. Furthermore, oral treatment with WIP from P. cocos significantly improved glucose and lipid metabolism and alleviated hepatic steatosis in ob/ob mice. 16S DNA sequencing analysis of cecum content from WIP-treated mice indicated the increase of butyrate-producing bacteria Lachnospiracea, Clostridium. It was also observed that WIP treatment elevated the level of butyrate in gut, improved the gut mucosal integrity and activated the intestinal PPAR-γ pathway. Fecal transplantation experiments definitely confirmed the causative role of gut microbiota in mediating the benefits of WIP. It is the first report that the water insoluble polysaccharide from the sclerotium of P. cocos modulates gut microbiota to improve hyperglycemia and hyperlipidemia. Thereby, WIP from P. cocos, as a prebiotic, has the potential for the prevention or cure of metabolic diseases and may elucidate new mechanism for the efficacies of this traditional herbal medicine on the regulation of lipid and glucose metabolism.}, }
@article {pmid30700790, year = {2019}, author = {Miller, AW and Orr, T and Dearing, D and Monga, M}, title = {Loss of function dysbiosis associated with antibiotics and high fat, high sugar diet.}, journal = {The ISME journal}, volume = {13}, number = {6}, pages = {1379-1390}, pmid = {30700790}, issn = {1751-7370}, support = {F32 DK102277/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage/*adverse effects ; Bacteria/classification/drug effects/isolation &amp; purification/metabolism ; Diet, High-Fat/*adverse effects ; Dysbiosis/*etiology/metabolism/microbiology ; Gastrointestinal Microbiome/drug effects ; Humans ; Mice ; Oxalates/metabolism ; Sigmodontinae/microbiology ; Sugars/*adverse effects/metabolism ; }, abstract = {The incidence of urinary stone disease (USD) has increased four-fold in 50 years. Oxalate, which is degraded exclusively by gut bacteria, is an important constituent in 80% of urinary stones. We quantified the effects of antibiotics and a high fat/high sugar (HFHS) diet on the microbial metabolism of oxalate in the gut. High and low oxalate-degrading mouse models were developed by administering fecal transplants from either the wild mammalian rodent Neotoma albigula or Swiss-Webster mice to Swiss-Webster mice, which produces a microbiota with or without the bacteria necessary for persistent oxalate metabolism, respectively. Antibiotics led to an acute loss of both transplant bacteria and associated oxalate metabolism. Transplant bacteria exhibited some recovery over time but oxalate metabolism did not. In contrast, a HFHS diet led to an acute loss of function coupled with a gradual loss of transplant bacteria, indicative of a shift in overall microbial metabolism. Thus, the effects of oral antibiotics on the microbiome form and function were greater than the effects of diet. Results indicate that both antibiotics and diet strongly influence microbial oxalate metabolism.}, }
@article {pmid30700573, year = {2019}, author = {Zmora, N and Soffer, E and Elinav, E}, title = {Transforming medicine with the microbiome.}, journal = {Science translational medicine}, volume = {11}, number = {477}, pages = {}, doi = {10.1126/scitranslmed.aaw1815}, pmid = {30700573}, issn = {1946-6242}, mesh = {Animals ; Diet ; Fecal Microbiota Transplantation ; Gastrointestinal Tract/drug effects ; Humans ; *Microbiota/drug effects ; *Precision Medicine ; Probiotics/pharmacology ; }, abstract = {Advances in microbiome research are spurring the development of new therapeutics for a variety of diseases, but translational challenges remain.}, }
@article {pmid30700514, year = {2019}, author = {Leslie, JL and Vendrov, KC and Jenior, ML and Young, VB}, title = {The Gut Microbiota Is Associated with Clearance of Clostridium difficile Infection Independent of Adaptive Immunity.}, journal = {mSphere}, volume = {4}, number = {1}, pages = {}, pmid = {30700514}, issn = {2379-5042}, support = {T32 AI007528/AI/NIAID NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; }, mesh = {*Adaptive Immunity ; Animals ; Antibody Formation ; Clostridioides difficile/*growth &amp; development ; Clostridium Infections/*immunology/*microbiology ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Immunity, Cellular ; Mice ; *Microbial Interactions ; }, abstract = {Clostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor for Clostridium difficile infection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80 to 90% success rate of fecal microbial transplants in treating recurrent infections. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance of C. difficile has yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance of C. difficile However, random forest analysis using only two members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance of C. difficile from the murine gastrointestinal tract.IMPORTANCEClostridium difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently, the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance of C. difficile from the GI tract. Our results show that clearance of C. difficile can occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens, as inherent differences in the baseline community structure of animals may bias findings.}, }
@article {pmid30700240, year = {2019}, author = {Marchukov, D and Misselwitz, B}, title = {[Insights into the Pathogenesis of Inflammatory Bowel Diseases: Genetics and Microbiota].}, journal = {Therapeutische Umschau. Revue therapeutique}, volume = {75}, number = {5}, pages = {273-279}, doi = {10.1024/0040-5930/a000999}, pmid = {30700240}, issn = {0040-5930}, mesh = {Genome-Wide Association Study ; Humans ; *Inflammatory Bowel Diseases/genetics/microbiology ; *Microbiota ; }, abstract = {Insights into the Pathogenesis of Inflammatory Bowel Diseases: Genetics and Microbiota Abstract. An inadequate immune response against bacteria of the gastrointestinal tract is the basic mechanism mediating the pathophysiology of inflammatory bowel diseases (IBD). The risk of IBD is partially heritable and approximately 12 % of patients have a family history of IBD. Large genome-wide association studies (GWAS) were able to identify 240 genetic regions associated with IBD. Many of the implicated genes have a function in the immune system, are associated with primary immunodeficiencies or the defense against mycobacteria. Together these 240 genetic regions form an excellent framework for further investigations into the pathogenesis and therapy of IBD. However, GWAS so far were able to unravel only a fraction of the genetic IBD risk. New strategies like genome wide sequencing are currently used to identify additional (rare) genetic variants. In rare cases, IBD is also inherited as a monogenetic disease. Moreover, there likely is significant interaction between genes and environmental factors which can only be unraveled if both, genes and the environment are simultaneously considered. Interestingly, the information provided by genetic risk factors for IBD is unable to predict the clinical course of IBD. New GWAS therefore focus on IBD prognosis and first insights have already been made. The gastrointestinal tract harbors a huge number of microorganisms (microbiota). It remains an enormous challenge for the immune system to contain this bacterial load while enabling the host to benefit from the many essential contributions of the microbiota. In IBD, the microbiota is altered to a dysfunctional (dysbiotic) state showing reduced diversity and a higher amount of potential pathogenic Proteobacteriae, such as Escherichia coli. In IBD, the microbiota is also more dynamic in its composition over time compared to health. Further, IBD dysbiosis is more pronounced in Crohn's disease than in ulcerative colitis. In animal experiments, dysbiosis could be transferred by fecal microbiota transplantation from one mouse to another, triggering inflammation in the recipient. In contrast, a healthy microbiota can downregulate the immune response of the host, for instance by bacterial short chain fatty acids (SCFA) synthesis. In addition, some bacteria with close physical contact to the intestinal wall also have specific immunosuppressive properties. So far, the highly complex network of microbiota, genetics, immune system and environment is only partially understood. The microbiota is a potential therapeutic target which up to now can only be non-specifically influenced by antibiotics, probiotics, prebiotics or fecal microbiota transplantation. A better understanding of the microbiota will likely yield in the discovery of new therapeutic options in the future.}, }
@article {pmid30696986, year = {2019}, author = {Castellani, C and Singer, G and Eibisberger, M and Obermüller, B and Warncke, G and Miekisch, W and Kolb-Lenz, D and Summer, G and Pauer, TM and ElHaddad, A and Kashofer, K and Till, H}, title = {The effects of neuroblastoma and chemotherapy on metabolism, fecal microbiome, volatile organic compounds, and gut barrier function in a murine model.}, journal = {Pediatric research}, volume = {85}, number = {4}, pages = {546-555}, pmid = {30696986}, issn = {1530-0447}, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Cyclophosphamide/*pharmacology ; Disease Models, Animal ; Feces/*microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intestinal Mucosa/*metabolism ; Mice ; Mice, Nude ; Neuroblastoma/*metabolism ; Volatile Organic Compounds/*metabolism ; }, abstract = {BACKGROUND: Following transplantation of human neuroblastoma (NB) cells into athymic mice, we investigated the effects of tumor growth and cyclophosphamide (CTX) treatment on systemic metabolism, gut inflammation and permeability, fecal microbiome and volatile organic compounds (VOCs).<br><br>METHODS: NB cells (MHH-NB11) were implanted into athymic mice (n=20); 20 healthy mice served as controls (sham).&#xa0; CTX was given to 20 animals (10 NB&#xa0;and 10 sham)&#xa0;after 8 and 9 weeks. Metabolic changes were measured. Ileum samples were obtained for RT-PCR (claudins 2 and 4, occludin, tight junction protein 1) and apoptosis rate determination. Fecal microbiome and VOCs were analyzed. Values were compared to sham animals.<br><br>RESULTS: NB caused reduction of adipose tissue, increases of IL-6 and TNF-&#x3b1;, and decreases of TGF-&#x3b2;1 and -&#x3b2;2. Serum FITC-dextrane levels were increased in NB and improved under CTX. Claudin 4 expression was higher in NB versus NB&#x2009;+&#x2009;CTX and sham animals. NB caused increased apoptosis of epithelial cells. NB but also CTX led to a reduction in the abundance of Lactobacillus. NB led to alterations of the fecal VOC profile.<br><br>CONCLUSIONS: NB caused a catabolic pro-inflammatory state, increased gut permeability, altered fecal VOCs and reductions of Lactobacillus. Further investigations are required to determine if modifications of the intestinal microbiome may reverse some of the observed effects.}, }
@article {pmid30696914, year = {2019}, author = {Carlucci, C and Jones, CS and Oliphant, K and Yen, S and Daigneault, M and Carriero, C and Robinson, A and Petrof, EO and Weese, JS and Allen-Vercoe, E}, title = {Effects of defined gut microbial ecosystem components on virulence determinants of Clostridioides difficile.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {885}, pmid = {30696914}, issn = {2045-2322}, support = {R21 AI121575/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Bacterial Toxins/pharmacology ; Ciprofloxacin/pharmacology ; Clostridiales/genetics/metabolism ; Clostridioides difficile/*genetics/metabolism ; Clostridium Infections/microbiology ; Diarrhea/microbiology ; Dysbiosis/microbiology ; Enterotoxins/pharmacology ; Fecal Microbiota Transplantation/methods ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics ; Humans ; Microbiota/genetics ; Virulence/genetics ; Virulence Factors/pharmacology ; }, abstract = {Many cases of Clostridioides difficile infection (CDI) are poorly responsive to standard antibiotic treatment strategies, and often patients suffer from recurrent infections characterized by severe diarrhea. Our group previously reported the successful cure of two patients with recurrent CDI using a standardized stool-derived microbial ecosystem therapeutic (MET-1). Using an in vitro model of the distal gut to support bacterial communities, we characterized the metabolite profiles of two defined microbial ecosystems derived from healthy donor stool (DEC58, and a subset community, MET-1), as well as an ecosystem representative of a dysbiotic state (ciprofloxacin-treated DEC58). The growth and virulence determinants of two C. difficile strains were then assessed in response to components derived from the ecosystems. CD186 (ribotype 027) and CD973 (ribotype 078) growth was decreased upon treatment with DEC58 metabolites compared to ciprofloxacin-treated DEC58 metabolites. Furthermore, CD186 TcdA and TcdB secretion was increased following treatment with ciprofloxacin-treated DEC58 spent medium compared to DEC58 spent medium alone. The net metabolic output of C. difficile was also modulated in response to spent media from defined microbial ecosystems, although several metabolite levels were divergent across the two strains examined. Further investigation of these antagonistic properties will guide the development of microbiota-based therapeutics for CDI.}, }
@article {pmid30696813, year = {2019}, author = {Jianguo, L and Xueyang, J and Cui, W and Changxin, W and Xuemei, Q}, title = {Altered gut metabolome contributes to depression-like behaviors in rats exposed to chronic unpredictable mild stress.}, journal = {Translational psychiatry}, volume = {9}, number = {1}, pages = {40}, pmid = {30696813}, issn = {2158-3188}, mesh = {Animals ; Behavior, Animal ; Depression/etiology/*metabolism/*microbiology ; *Feces/microbiology ; *Gastrointestinal Microbiome ; Male ; Metabolome ; Rats, Sprague-Dawley ; Stress, Psychological/*complications ; }, abstract = {The gut microbiota has been increasingly correlated with depressive disorder. It was recently shown that the transplantation of the gut microbiota from depressed patients to animals can produce depressive-like behaviors, suggesting that the gut microbiota plays a causal role in the development of depression. In addition, metabolic disorder, which is strongly associated with depression, is exacerbated by changes in the composition of the gut microbiota and is alleviated by treatment with antidepressants. However, the key players and pathways that link the gut microbiota to the pathogenesis of depression remain largely unknown. To evaluate the relationships between depression and metabolic disorders in feces and plasma, we monitored changes in fecal and plasma metabolomes during the development of depressive-like behaviors in rats exposed to chronic unpredictable mild stress (CUMS). In these animals, the fecal metabolome was altered first and subjected to changes in the plasma metabolome. Changes in the abundance of fecal metabolites were associated with depressive-like behaviors and with altered levels of neurotransmitters in the hippocampus. Furthermore, the analysis of the fecal metabolome and the fecal microbiota in CUMS rats demonstrated consistent changes in the levels of several amino acids, including L-threonine, isoleucine, alanine, serine, tyrosine, and oxidized proline. Finally, we observed significant correlations between these amino acids and the altered fecal microbiota. The results of this study suggest that changes in amino acid metabolism by the gut microbiota contribute to changes in circulating amino acids and are associated with the behavior indices of depression.}, }
@article {pmid30694953, year = {2019}, author = {Rancich, M and Roman, C}, title = {Updated guidelines for diagnosing and managing Clostridium difficile.}, journal = {JAAPA : official journal of the American Academy of Physician Assistants}, volume = {32}, number = {2}, pages = {48-50}, doi = {10.1097/01.JAA.0000552734.33929.01}, pmid = {30694953}, issn = {1547-1896}, mesh = {Anti-Bacterial Agents/*standards/therapeutic use ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*therapy ; Fecal Microbiota Transplantation/*standards ; Humans ; Metronidazole/*standards/therapeutic use ; Practice Guidelines as Topic ; }, abstract = {The updated Infectious Disease Society of America guidelines for managing Clostridium difficile infections remove metronidazole as first-line therapy and add fecal microbiota transplants to the treatment options. This article reviews the new guidelines and strategies for diagnosis and infection control.}, }
@article {pmid30694100, year = {2019}, author = {Stadlbauer, V and Horvath, A and Komarova, I and Schmerboeck, B and Feldbacher, N and Klymiuk, I and Durdevic, M and Rainer, F and Blesl, A and Stiegler, P and Leber, B}, title = {Dysbiosis in early sepsis can be modulated by a multispecies probiotic: a randomised controlled pilot trial.}, journal = {Beneficial microbes}, volume = {10}, number = {3}, pages = {265-278}, doi = {10.3920/BM2018.0067}, pmid = {30694100}, issn = {1876-2891}, mesh = {Bacteria/classification/genetics ; Bacterial Translocation/drug effects ; Biodiversity ; Double-Blind Method ; Dysbiosis/*drug therapy ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intestinal Mucosa/drug effects ; Male ; Middle Aged ; Pilot Projects ; Probiotics/*administration &amp; dosage/*pharmacology ; Sepsis/*drug therapy ; Treatment Outcome ; }, abstract = {The gut is hypothesised to play an important role in the development and progression of sepsis. It is however unknown whether the gut microbiome and the gut barrier function is already altered early in sepsis development and whether it is possible to modulate the microbiome in early sepsis. Therefore, a randomised, double blind, placebo-controlled pilot study to examine the alterations of the microbiome and the gut barrier in early sepsis and the influence of a concomitant probiotic intervention on dysbiosis at this early stage of the disease was conducted. Patients with early sepsis, defined as fulfilling the sepsis definition from the 2012 Surviving Sepsis Campaign guidelines but without signs of organ failure, received multispecies probiotic (Winclove 607 based on Omnibiotic® 10 AAD) for 28 days. Gut microbiome composition, function, gut barrier and bacterial translocation were studied. Patients with early sepsis had a significantly lower structural and functional alpha diversity, clustered differently and showed structural alterations on all taxonomic levels. Gut permeability was unaltered but endotoxin, endotoxin binding proteins and peptidoglycans were elevated in early sepsis patients compared to controls. Probiotic intervention successfully increased probiotic strains in stool and led to an improvement of functional diversity. Microbiome composition and function are altered in early sepsis. Probiotic intervention successfully modulates the microbiome and is therefore a promising tool for early intervention in sepsis.}, }
@article {pmid30692975, year = {2018}, author = {Le Roy, T and Debédat, J and Marquet, F and Da-Cunha, C and Ichou, F and Guerre-Millo, M and Kapel, N and Aron-Wisnewsky, J and Clément, K}, title = {Comparative Evaluation of Microbiota Engraftment Following Fecal Microbiota Transfer in Mice Models: Age, Kinetic and Microbial Status Matter.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3289}, pmid = {30692975}, issn = {1664-302X}, abstract = {The intestinal microbiota and its functions are intricately interwoven with host physiology. Colonizing rodents with donor microbiota provides insights into host-microbiota interactions characterization and the understanding of disease physiopathology. However, a better assessment of inoculation methods and recipient mouse models is needed. Here, we compare the engraftment at short and long term of genetically obese mice microbiota in germ-free (GF) mice and juvenile and adult specific pathogen free (SPF) mice. We also tested the effects of initial microbiota depletion before microbiota transfer. In the present work, donor microbiota engraftment was better in juvenile SPF mice than in adult SPF mice. In juvenile mice, initial microbiota depletion using laxatives or antibiotics improved donor microbiota engraftment 9 weeks but not 3 weeks after microbiota transfer. Microbiota-depleted juvenile mice performed better than GF mice 3 weeks after the microbiota transfer. However, 9 weeks after transfer, colonized GF mice microbiota had the lowest Unifrac distance to the donor microbiota. Colonized GF mice were also characterized by a chronic alteration in intestinal absorptive function. With these collective results, we show that the use of juvenile mice subjected to initial microbiota depletion constitutes a valid alternative to GF mice in microbiota transfer studies.}, }
@article {pmid30689972, year = {2019}, author = {Randel, KR and Botteri, E and Romstad, KMK and Frigstad, SO and Bretthauer, M and Hoff, G and de Lange, T and Holme, &#xd8;}, title = {Effects of Oral Anticoagulants and Aspirin on Performance of Fecal Immunochemical Tests in Colorectal Cancer Screening.}, journal = {Gastroenterology}, volume = {156}, number = {6}, pages = {1642-1649.e1}, doi = {10.1053/j.gastro.2019.01.040}, pmid = {30689972}, issn = {1528-0012}, mesh = {Adenoma/*diagnosis ; Administration, Oral ; Aged ; Anticoagulants/*administration &amp; dosage ; Aspirin/*administration &amp; dosage ; Colonoscopy ; Colorectal Neoplasms/*diagnosis ; Cross-Sectional Studies ; Early Detection of Cancer/*methods ; Female ; Humans ; Immunochemistry ; Male ; Middle Aged ; *Occult Blood ; Platelet Aggregation Inhibitors/*administration &amp; dosage ; Predictive Value of Tests ; Warfarin/administration &amp; dosage ; }, abstract = {BACKGROUND &amp; AIMS: The fecal immunochemical test (FIT) is the tool most frequently used for colorectal cancer (CRC) screening worldwide. It is unclear how the use of aspirin and oral anticoagulants in the screening population affects the diagnostic performance of FIT.<br><br>METHODS: We performed a cross-sectional study in an ongoing CRC screening trial in Norway. Participants aged 50-74 years with a positive result from an FIT (>15 &#x3bc;g hemoglobin/g feces) and subsequent colonoscopy (reference standard) were included. Those who used regular aspirin, warfarin, or direct-acting oral anticoagulants (DOACs) were defined as users. Non-users were matched according to age, sex, screening center, and screening round. The primary outcomes were the positive predictive value (PPV) for CRC and advanced adenoma.<br><br>RESULTS: Among 4908 eligible participants, 1008 used aspirin, 147 used warfarin, 212 used DOACs, and 3541 were non-users. CRCs were found in 234 individuals and advanced adenomas in 1305 individuals. The PPV for CRC was 3.8% for aspirin users vs 6.4% for matched non-users (P&#xa0;= .006), The PPV for advanced adenoma in aspirin users was 27.2% vs 32.6% for matched non-users (P&#xa0;= .011). For DOAC, the PPV for CRC was 0.9% in users vs 6.8% in matched non-users (P&#xa0;= .001). The PPV for advanced adenoma in DOAC users was 20.5% vs 32.4% in matched non-users (P&#xa0;= .002). There was no significant difference in PPV for CRC or advanced adenoma in warfarin users compared to non-users.<br><br>CONCLUSIONS: In a large screening cohort in Norway, regular use of aspirin and particularly DOACs, were associated with lower PPV of FIT for detection of CRCs and advanced adenomas. ClinicalTrials.gov ID NCT01538550.}, }
@article {pmid30689174, year = {2019}, author = {Dinleyici, M and Vandenplas, Y}, title = {Clostridium difficile Colitis Prevention and Treatment.}, journal = {Advances in experimental medicine and biology}, volume = {1125}, number = {}, pages = {139-146}, doi = {10.1007/5584_2018_322}, pmid = {30689174}, issn = {0065-2598}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; Clostridium Infections/*prevention &amp; control/*therapy ; Diarrhea/prevention &amp; control/therapy ; Enterocolitis, Pseudomembranous/*prevention &amp; control/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Probiotics/*therapeutic use ; }, abstract = {Clostridium difficile (C. diff) is the most common causative agent of antibiotic-associated diarrhea and colitis. This spore-forming, obligate anaerobic, gram-positive bacillus is becoming responsible for an increasing number of infections worldwide, both in community and in hospital settings, whose severity can vary widely from an asymptomatic infection to a lethal disease. While discontinuation of antimicrobial agents and antibiotic treatment of the infection remain the cornerstone of therapy, the use of probiotics, especially Saccharomyces boulardii, and more recently of fecal microbiota transplantation have become valid forms of prevention and/or therapy and are here critically examined.}, }
@article {pmid30689151, year = {2019}, author = {Afouda, P and Traore, SI and Dione, N and Andrieu, C and Tomei, E and Richez, M and Di Pinto, F and Lagier, JC and Dubourg, G and Raoult, D and Fournier, PE}, title = {Description and genomic characterization of Massiliimalia massiliensis gen. nov., sp. nov., and Massiliimalia timonensis gen. nov., sp. nov., two new members of the family Ruminococcaceae isolated from the human gut.}, journal = {Antonie van Leeuwenhoek}, volume = {112}, number = {6}, pages = {905-918}, doi = {10.1007/s10482-018-01223-x}, pmid = {30689151}, issn = {1572-9699}, support = {10-IAHU-03//Fondation M&#xe9;diterran&#xe9;e Infection/ ; }, mesh = {Base Composition ; Clostridiales/classification/genetics/*isolation &amp; purification ; DNA, Bacterial/genetics ; Feces/*microbiology ; Gastrointestinal Microbiome ; Genome Size ; *Genome, Bacterial ; Genomics ; Humans ; Male ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Saudi Arabia ; Young Adult ; }, abstract = {Using the culturomics approach, we isolated two strains, Marseille-P2963 and Marseille-P3753, from the intestinal microbiota of a 19-year-old healthy Saudi Arabian Bedouin male and from a 32-year-old healthy Senegalese male faecal transplant donor. Here, we studied their phenotypic, phylogenetic and genomic characteristics. Both strains were phylogenetically related, but different from Ruminococcus species. Bacterial cells were anaerobic, rod-shaped, non-spore-forming and not motile, with neither catalase nor oxidase activities. Their growth temperatures ranged from 28 to 45 °C, with an optimal growth at 37 °C. The genomes are 2,842,720 bp- and 2,707,061 bp-long respectively. The G + C contents are 47.18% and 46.90%, respectively. Based on these characteristics, we propose the creation of a new genus within the family Ruminococcaceae named Massiliimalia gen. nov., that contains the new species Massiliimalia massiliensis gen. nov., sp. nov., and Massiliimalia timonensis gen. nov., sp. nov. Strains Marseille-P2963[T] (= CSUR P2963 = DSM 106837) and Marseille-P3753[T] (= CSUR P3753 = CCUG 71632) are their type strains, respectively.}, }
@article {pmid30687932, year = {2019}, author = {Yoshikawa, T and Ihira, M and Higashimoto, Y and Hattori, F and Miura, H and Sugata, K and Komoto, S and Taniguchi, K and Iguchi, A and Yamada, M and Ariga, T}, title = {Persistent systemic rotavirus vaccine infection in a child with X-linked severe combined immunodeficiency.}, journal = {Journal of medical virology}, volume = {91}, number = {6}, pages = {1008-1013}, doi = {10.1002/jmv.25410}, pmid = {30687932}, issn = {1096-9071}, mesh = {Feces/virology ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Male ; Phylogeny ; RNA, Viral/blood/genetics ; Rotavirus/genetics ; Rotavirus Infections/*blood/*etiology ; Rotavirus Vaccines/*adverse effects ; Viral Load ; X-Linked Combined Immunodeficiency Diseases/*complications/*virology ; }, abstract = {OBJECTIVE: The main aims of the present study were to elucidate the systemic group A rotavirus (RVA) infection and to clarify the genetic changes of persistent virus in the X-linked severe combined immunodeficiency (SCID) patient.<br><br>METHODS: RotaTeq vaccine (RV5) genotype-specific real-time reverse transcription polymerase chain reaction was used to monitor viral RNA load in serially collected serum and stool samples. Next-generation sequence analysis was used to determine the genotype of the virus by sequencing 11 gene segments. Polyacrylamide gel electrophoresis (PAGE) analysis was used to identify rearrangement of viral genes. The gene rearrangement was examined in NSP5 gene by using Sanger sequence.<br><br>RESULTS: A 7-month-old boy demonstrated chronic diarrhea following the third administration of RV5 and failure to thrive. He was diagnosed with X-linked SCID and successfully underwent cord blood transplantation. High copy numbers of RV5 genotype G1 RNA were detected in serially collected stool and serum samples and the kinetics of viral RNA loads were correlated with the degree of clinical disease. Next-generation sequence analysis revealed genetic reassortment at least between the strains WI79-9/G1P7[5] and WI79-4/G6P1A[8] in the VP7 gene and the VP4 gene among the vaccine-derived rotavirus strains. In addition, PAGE analysis suggested genetic rearrangements in several genes, and it was confirmed in the NSP5 gene by sequence analysis.<br><br>CONCLUSIONS: The kinetics of RVA RNA load in serum and stool samples was consistent with the clinical course of the patient. Among five genotypes of RV5 vaccine, G1 genotype replicated well in this patient. Reassortment and rearrangements were demonstrated in persistently infected G1 genotype of RV5.}, }
@article {pmid30687107, year = {2018}, author = {Basso, PJ and Câmara, NOS and Sales-Campos, H}, title = {Microbial-Based Therapies in the Treatment of Inflammatory Bowel Disease - An Overview of Human Studies.}, journal = {Frontiers in pharmacology}, volume = {9}, number = {}, pages = {1571}, pmid = {30687107}, issn = {1663-9812}, abstract = {Inflammatory bowel disease (IBD) is a group of multifactorial and inflammatory infirmities comprised of two main entities: Ulcerative colitis (UC) and Crohn's disease (CD). Classic strategies to treat IBD are focused on decreasing inflammation besides inducing and extending disease remission. However, these approaches have several limitations such as low responsiveness, excessive immunosuppression, and refractoriness. Despite the multifactorial causality of IBD, immune disturbances and intestinal dysbiosis have been suggested as the central players in disease pathogenesis. Hence, therapies aiming at modulating intestinal microbial composition may represent a promising strategy in IBD control. Fecal microbiota transplantation (FMT) and probiotics have been explored as promising candidates to reestablish microbial balance in several immune-mediated diseases such as IBD. These microbial-based therapies have demonstrated the ability to reduce both the dysbiotic environment and production of inflammatory mediators, thus inducing remission, especially in UC. Despite these promising results, there is still no consensus on the relevance of such treatments in IBD as a potential clinical strategy. Thus, this review aims to critically review and describe the use of FMT and probiotics to treat patients with IBD.}, }
@article {pmid30685497, year = {2019}, author = {Mullish, BH and Ghani, R and McDonald, JAK and Marchesi, JR}, title = {Faecal microbiota transplant for eradication of multidrug-resistant Enterobacteriaceae: a lesson in applying best practice? Re: 'A five-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: A Randomized Clinical Trial'.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {25}, number = {7}, pages = {912-913}, doi = {10.1016/j.cmi.2019.01.010}, pmid = {30685497}, issn = {1469-0691}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Anti-Bacterial Agents ; Enterobacteriaceae ; *Enterobacteriaceae Infections ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid30683453, year = {2019}, author = {Ghosh, C and Sarkar, P and Issa, R and Haldar, J}, title = {Alternatives to Conventional Antibiotics in the Era of Antimicrobial Resistance.}, journal = {Trends in microbiology}, volume = {27}, number = {4}, pages = {323-338}, doi = {10.1016/j.tim.2018.12.010}, pmid = {30683453}, issn = {1878-4380}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antimicrobial Cationic Peptides/therapeutic use ; Bacterial Infections/*therapy ; Bacteriocins/therapeutic use ; Bacteriophages ; Biological Therapy/*methods ; Biotechnology ; CRISPR-Cas Systems ; Disease Models, Animal ; *Drug Resistance, Bacterial/drug effects ; Fecal Microbiota Transplantation ; Genetic Engineering ; Humans ; Microbiota ; Oligonucleotides/therapeutic use ; Phage Therapy/methods ; Probiotics/therapeutic use ; }, abstract = {As more antibiotics are rendered ineffective by drug-resistant bacteria, focus must be shifted towards alternative therapies for treating infections. Although several alternatives already exist in nature, the challenge is to implement them in clinical use. Advancements within biotechnology, genetic engineering, and synthetic chemistry have opened up new avenues towards the search for therapies that can substitute for antibiotics. This review provides an introduction to the various promising approaches that have been adopted in this regard. Whilst the use of bacteriophages and antibodies has been partly implemented, other promising strategies, such as probiotics, lysins, and antimicrobial peptides, are in various stages of development. Propitious concepts such as genetically modified phages, antibacterial oligonucleotides, and CRISPR-Cas9 are also discussed.}, }
@article {pmid30681907, year = {2019}, author = {Morris, DJ and Brem, AS}, title = {Role of gut metabolism of adrenal corticosteroids and hypertension: clues gut-cleansing antibiotics give us.}, journal = {Physiological genomics}, volume = {51}, number = {3}, pages = {83-89}, doi = {10.1152/physiolgenomics.00115.2018}, pmid = {30681907}, issn = {1531-2267}, mesh = {11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists &amp; inhibitors/metabolism ; 11-beta-Hydroxysteroid Dehydrogenase Type 2/antagonists &amp; inhibitors/metabolism ; Animals ; Anti-Bacterial Agents/*therapeutic use ; Blood Pressure/drug effects ; Corticosterone/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Glucocorticoids/*metabolism ; Humans ; Hydrocortisone/metabolism ; Hypertension/*drug therapy/*microbiology ; Intestinal Mucosa/drug effects/*metabolism ; Mice ; Rats ; }, abstract = {Intestinal bacteria can metabolize sterols, bile acids, steroid hormones, dietary proteins, fiber, foodstuffs, and short chain fatty acids. The metabolic products generated by some of these intestinal bacteria have been linked to a number of systemic diseases including obesity with Type 2 diabetes mellitus, some forms of inflammation, and more recently, systemic hypertension. In this review, we primarily focus on the potential role selected gut bacteria play in metabolizing the endogenous glucocorticoids corticosterone and cortisol. Those generated steroid metabolites, when reabsorbed in the intestine back into the circulation, produce biological effects most notably as inhibitors of 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2. Inhibition of the dehydrogenase actions of 11β-HSD, particularly in kidney and vascular tissue, allows both corticosterone and cortisol the ability to bind to and activate mineralocorticoid receptors with attended changes in sodium handling and vascular resistance leading to increases in blood pressure. In several animal models of hypertension, administration of gut-cleansing antibiotics results in transient resolution of hypertension and transfer of intestinal contents from a hypertensive animal to a normotensive animal produces hypertension in the recipient. Moreover, fecal samples from hypertensive humans transplanted into germ-free mice resulted in hypertension in the recipient mice. Thus, it appears that the intestinal microbiome may not just be an innocent bystander but certain perturbations in the type and number of bacteria may directly or indirectly affect hypertension and other diseases.}, }
@article {pmid30680947, year = {2019}, author = {Zhang, J and Bi, JJ and Guo, GJ and Yang, L and Zhu, B and Zhan, GF and Li, S and Huang, NN and Hashimoto, K and Yang, C and Luo, AL}, title = {Abnormal composition of gut microbiota contributes to delirium-like behaviors after abdominal surgery in mice.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {25}, number = {6}, pages = {685-696}, pmid = {30680947}, issn = {1755-5949}, mesh = {Abdomen/*surgery ; Animals ; Biodiversity ; Delirium/*microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Germ-Free Life ; Male ; Mice, Inbred C57BL ; Postoperative Complications/*microbiology ; Random Allocation ; }, abstract = {AIMS: Anesthesia and surgery can cause delirium-like symptoms postoperatively. Increasing evidence suggests that gut microbiota is a physiological regulator of the brain. Herein, we investigated whether gut microbiota plays a role in postoperative delirium (POD).<br><br>METHODS: Mice were separated into non-POD and POD phenotypes after abdominal surgery by applying hierarchical clustering analysis to behavioral tests. Fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition among sham, non-POD, and POD mice. Fecal bacteria from non-POD and POD mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on behaviors.<br><br>RESULTS: &#x3b1;-diversity and &#x3b2;-diversity indicated differences in gut microbiota composition between the non-POD and POD mice. At the phylum level, the non-POD mice had significantly higher levels of Tenericutes, which were not detected in the POD mice. At the class level, levels of Gammaproteobacteria were higher in the POD mice, whereas the non-POD mice had significantly higher levels of Mollicutes, which were not detected in the POD mice. A total of 20 gut bacteria differed significantly between the POD and non-POD mice. Interestingly, the pseudo-germ-free mice showed abnormal behaviors prior to transplant. The pseudo-germ-free mice that received fecal bacteria transplants from non-POD mice but not from POD mice showed improvements in behaviors.<br><br>CONCLUSIONS: Abnormal gut microbiota composition after abdominal surgery may contribute to the development of POD. A therapeutic strategy that targets gut microbiota could provide a novel alterative for POD treatment.}, }
@article {pmid30680920, year = {2019}, author = {Porras, D and Nistal, E and Martínez-Flórez, S and Olcoz, JL and Jover, R and Jorquera, F and González-Gallego, J and García-Mediavilla, MV and Sánchez-Campos, S}, title = {Functional Interactions between Gut Microbiota Transplantation, Quercetin, and High-Fat Diet Determine Non-Alcoholic Fatty Liver Disease Development in Germ-Free Mice.}, journal = {Molecular nutrition &amp; food research}, volume = {63}, number = {8}, pages = {e1800930}, doi = {10.1002/mnfr.201800930}, pmid = {30680920}, issn = {1613-4133}, mesh = {Animals ; Diet, High-Fat/*adverse effects ; Endotoxemia/etiology/therapy ; Fatty Acids, Volatile/metabolism ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Inflammasomes ; Insulin Resistance ; Liver/drug effects/pathology ; Male ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/microbiology/*prevention &amp; control ; Obesity/complications/drug therapy/microbiology ; Quercetin/*pharmacology ; Verrucomicrobia/physiology ; }, abstract = {SCOPE: Modulation of intestinal microbiota has emerged as a new therapeutic approach for non-alcoholic fatty liver disease (NAFLD). Herein, it is addressed whether gut microbiota modulation by quercetin and intestinal microbiota transplantation can influence NAFLD development.<br><br>METHODS AND RESULTS: Gut microbiota donor mice are selected according to their response to high-fat diet (HFD) and quercetin in terms of obesity and NAFLD-related biomarkers. Germ-free recipients displayed metabolic phenotypic differences derived from interactions between microbiota transplanted, diets, and quercetin. Based on the evaluation of hallmark characteristics of NAFLD, it is found that gut microbiota transplantation from the HFD-non-responder donor and the HFD-fed donor with the highest response to quercetin results in a protective phenotype against HFD-induced NAFLD, in a mechanism that involves gut-liver axis alteration blockage in these receivers. Gut microbiota from the HFD-responder donor predisposed transplanted germ-free mice to NAFLD. Divergent protective and deleterious metabolic phenotypes exhibited are related to definite microbial profiles in recipients, highlighting the predominant role of Akkermansia genus in the protection from obesity-associated NAFLD development.<br><br>CONCLUSIONS: The results provide scientific support for the prebiotic capacity of quercetin and the transfer of established metabolic profiles through gut microbiota transplantation as a protective strategy against the development of obesity-related NAFLD.}, }
@article {pmid30679532, year = {2019}, author = {Kim, JH and Kim, K and Kim, W}, title = {Cream Cheese-Derived Lactococcus chungangensis CAU 28 Modulates the Gut Microbiota and Alleviates Atopic Dermatitis in BALB/c Mice.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {446}, pmid = {30679532}, issn = {2045-2322}, mesh = {Animals ; Cheese/*microbiology ; Dermatitis, Atopic/*immunology/therapy ; Diet ; Fatty Acids/immunology/metabolism ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; Gene Expression/immunology ; Ileum/immunology/metabolism ; Lactococcus/*immunology ; Mice, Inbred BALB C ; MicroRNAs/genetics/immunology ; T-Lymphocytes, Regulatory/immunology/metabolism ; }, abstract = {Atopic dermatitis (AD) has a drastic impact on human health owing to complex skin, gut microbiota, and immune responses. Some lactic acid bacteria (LAB) are effective in ameliorating AD; however, the alleviative effects of dairy products derived from these LAB remain unclear. In this study, the efficacies of Lactococcus chungangensis CAU 28 (CAU 28) cream cheese and L. chungangensis CAU 28 dry cells were evaluated for treating AD in an AD mouse model. Overall, CAU 28 cream cheese administration was more effective against AD than L. chungangensis CAU 28 dry cells. Faeces from CAU 28 cream cheese-administered mice had increased short chain fatty acid, butyrate, acetate, and lactic acid levels, as well as butyrate-producing bacteria, including Akkermansia, Bacteroides, Lactobacillus, and Ruminococcus. Furthermore, oral CAU 28 cream cheese administration resulted in regulatory T cell (Treg)-mediated suppression of T helper type 2 (Th2) immune responses in serum and mRNA expression levels in the ileum. Oral CAU 28 cream cheese further reduced IgE levels, in addition to eosinophil and mast cell numbers. Therefore, CAU 28 cream cheese administration induced a coordinated immune response involving short-chain fatty acids and gut microbiota, indicating its potential for use as a supplement for AD mitigation.}, }
@article {pmid30678445, year = {2019}, author = {Fukuda, T and Naganuma, M and Kanai, T}, title = {Current new challenges in the management of ulcerative colitis.}, journal = {Intestinal research}, volume = {17}, number = {1}, pages = {36-44}, pmid = {30678445}, issn = {1598-9100}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory condition of the gastrointestinal tract. Although the cause of UC is postulated to be multifactorial in nature, including genetic predisposition, epithelial barrier defects, dysregulation of immune responses, and environmental factors, the specific pathogenesis of UC is still incompletely understood. In the treatment of UC so far, a method of suppressing immunity and treating it has been mainstream. Immunosuppressant drugs, including thiopurines (azathioprine or 6-mercaptopurine), anti-tumor necrosis factor-α (anti-TNF-α) antibody (infliximab and adalimumab), and calcineurin inhibitor, can be used in treat patients with corticosteroid-dependent and/or corticosteroid-refractory moderateto- severe UC. Recently, in addition to such a conventional therapeutic agent, golimumab, which is the first transgenic human monoclonal anti-TNF-α antibody to be fabricated, anti α-4/β-7 integrin antibody, and Janus kinase inhibitor have been reported to novel immunosuppressant therapy. Furthermore, other treatments with unique mechanisms different from immunosuppression, have also been suggested, including fecal microbiota transplantation and Indigo naturalis, which is a Chinese herbal medicine. We compared the features and efficacy of these new treatments. In this issue, the features and treatment options for these new treatments is reviewed.}, }
@article {pmid30678444, year = {2019}, author = {Cho, YS}, title = {Multi-session fecal microbiota transplantation using colonoscopy has favorable outcomes for the treatment of steroid-dependent ulcerative colitis.}, journal = {Intestinal research}, volume = {17}, number = {1}, pages = {6-8}, pmid = {30678444}, issn = {1598-9100}, }
@article {pmid30673716, year = {2019}, author = {Hui, W and Li, T and Liu, W and Zhou, C and Gao, F}, title = {Fecal microbiota transplantation for treatment of recurrent C. difficile infection: An updated randomized controlled trial meta-analysis.}, journal = {PloS one}, volume = {14}, number = {1}, pages = {e0210016}, pmid = {30673716}, issn = {1932-6203}, mesh = {Anti-Bacterial Agents/pharmacology ; Clostridioides difficile/drug effects/physiology ; Clostridium Infections/microbiology/*therapy ; Diarrhea/microbiology/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Humans ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome ; }, abstract = {OBJECTIVES: Although systematic evaluation has confirmed the efficacy of fresh fecal microbiota transplantation (FMT) for treatment of recurrent and/or refractory and/or relapse C. difficile infection (RCDI), it lacks the support of well-designed randomized controlled trials (RCTs), and the latest guidelines do not optimize the management of FMT. In this paper, we focus on an in-depth study of fresh FMT and fecal infusion times to guide clinical practice.<br><br>METHODS: We reviewed studies in PubMed, Medline, Embase, the Cochrane library and Cochrane Central written in English. The retrieval period was from the establishment of the databases to September 20th, 2018. The retrieval objects were published RCTs of RCDI treated by fresh FMT. The intervention group was fresh FMT group, while the control group included antibiotic therapy or placebo or frozen FMT or capsule. The primary and secondary outcomes were the clinical remission of diarrhea without relapse after 8-17 weeks and the occurrence of severe adverse events, respectively. Subgroup analysis analyzed the effect of single and multiple fecal infusions. Two authors independently completed the information extraction and assessed risk of bias and overall quality of the evidence.<br><br>RESULTS: 8 randomized controlled trials met the inclusion criteria, involving 537 patients (273 in the fresh FMT group and 264 in the control group). The recurrence rate of clinical diarrhea in the fresh FMT group was 11.0% (30/273), which was significantly lower than the control group (24.6%, 65/264; P < 0.05); the pooled relative risk (RR) was 0.38 (95%CI:0.16-0.87; I2 = 67%; P = 0.02) in the fresh FMT group, and the clinical heterogeneity was significant and random effects model was used; However, there was no significant difference neither for the effect of antibiotic treatment/frozen feces transplanted by enema (RR = 1.07; 95%CI: 0.64-1.80; I2 = 0%; P = 0.79) or capsule/frozen feces transplanted by colonoscopy (RR = 0.42; 95%CI: 0.05-3.94; I2 = 43%; P = 0.45) compared with fresh FMT. The subgroup analysis showed that FMT by multiple infusions could effectively and significantly (RR = 0.24; 95%CI:0.10-0.58; I2 = 0%; P = 0.001) improve the clinical diarrhea remission rate. Most mild to moderate adverse events caused by FMT were self-limited and could be quickly alleviated; no severe adverse events happened because of FMT.<br><br>CONCLUSIONS: Overall, the use of fresh feces for bacterial transplantation was the best efficiency for RCDI compared to antibiotic therapy or placebo. The fecal transmission method by enema was not ideal, but capsules or frozen feces transported by colonoscopy could be an alternative treatment compared to fresh FMT. For patients with severe RCDI, multiple fecal transplants can effectively improve their diarrhea remission rate. The focus of future research should be on how to standardize the production of capsules or frozen feces to better guide the clinical management of RCDI patients by FMT.}, }
@article {pmid30668308, year = {2019}, author = {Moskowitz, D and Adelstein, SA and Lucioni, A and Kobashi, KC and Lee, UJ}, title = {Practice patterns in the diagnosis and treatment of fecal incontinence with sacral neuromodulation: Can urologists impact this gap in care?.}, journal = {Turkish journal of urology}, volume = {45}, number = {1}, pages = {37-41}, pmid = {30668308}, issn = {2149-3235}, abstract = {OBJECTIVE: The prevalence of fecal incontinence (FI) is 8% in the United States. Many patients will not seek treatment and the condition is underdiagnosed. Sacral neuromodulation (SNM) is effective in treating FI, and so urologists can play a key role in its treatment. We examine the practice patterns and treatment of FI with SNM in our institution.<br><br>MATERIAL AND METHODS: The electronic medical record was queried for the proportion of patients seen for FI in the institution, the urology department, and among the female pelvic medicine and reconstructive surgery (FPMRS) urologists. The patients who underwent SNM for FI were evaluated for progression to second stage procedure.<br><br>RESULTS: The proportion of patients seen for FI is 0.96% in the institution as a whole, 7.9% in the urology department, and 17.9% among FPMRS urologists. Fourteen patients underwent first stage SNM for FI or dual urinary/fecal incontinence, and they all progressed to a second stage procedure. Thirteen of these were performed by FPMRS urologists.<br><br>CONCLUSION: In our institution, the proportion of patients seen for FI was lower than the prevalence of this condition. Because patients with urinary incontinence are more likely to have FI, urologists are in a unique position to identify these patients and offer treatment that can improve their quality of life. We acknowledge a gap in care of the patients with FI and an opportunity for urologists to help patients with this devastating yet treatable condition.}, }
@article {pmid30667386, year = {2018}, author = {De Sire, R and Talocco, C and Petito, V and Lopetuso, LR and Graziani, C and Gasbarrini, A and Scaldaferri, F}, title = {[Microbiota and inflammatory bowel disease: an update.].}, journal = {Recenti progressi in medicina}, volume = {109}, number = {12}, pages = {570-573}, doi = {10.1701/3082.30741}, pmid = {30667386}, issn = {2038-1840}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Precision Medicine/methods ; Probiotics/administration &amp; dosage ; }, abstract = {Over the last few years, the gut microbiota has been the focus of countless studies conducted both on mouse models and human population, aimed at analyzing its functions and interactions with the host, including nutrition, metabolic homeostasis, protection from infections and development of systemic and mucosal immunity both in inflammatory bowel disease (IBD) as well as other intestinal and extra-intestinal diseases. In IBD microbiota is impaired in overall composition and biodiversity, stability as well as functions. Microbial signature of IBD can be considered also a decrease in F. prausnitzii, increase of Proteonbacteria as well as the described increase of Candida albicans, Basidiomycota/Ascomycota ratio over Saccharomyces cerevisiae and of the Caudovirales over Microviridae. The indirect (through antibiotics, probiotics) and direct (through fecal microbiota transplantation) modulation of gut microbiota has relevant clinical implication in IBD management. In the near future role and clinical implication of gut microbiota characterization in the therapeutic personalized approach to IBD patients will eventually become clear.}, }
@article {pmid30667154, year = {2019}, author = {Li, X and Chen, P and Zhang, P and Chang, Y and Cui, M and Duan, J}, title = {Protein-Bound β-glucan from Coriolus Versicolor has Potential for Use Against Obesity.}, journal = {Molecular nutrition &amp; food research}, volume = {63}, number = {7}, pages = {e1801231}, doi = {10.1002/mnfr.201801231}, pmid = {30667154}, issn = {1613-4133}, mesh = {Agaricales/*chemistry ; Animals ; Anti-Obesity Agents/chemistry/*pharmacology ; Cytokines/blood ; Diet, High-Fat/adverse effects ; Drug Evaluation, Preclinical/methods ; Fecal Microbiota Transplantation ; Female ; Fungal Proteins/chemistry/pharmacology ; Gastrointestinal Microbiome/drug effects ; Gene Expression Regulation/drug effects ; Inflammation/drug therapy/metabolism ; Mice, Inbred C57BL ; Obesity/etiology/*prevention &amp; control/therapy ; Verrucomicrobia/drug effects ; beta-Glucans/*chemistry/*pharmacology ; }, abstract = {SCOPE: The prevalence of obesity and related disorders has vastly increased throughout the world and prevention of such circumstances thus represents a major challenge. Here, it has been shown that one protein-bound β-glucan (PBG) from the edible mushroom Coriolus versicolor can be a potent anti-obesity component.<br><br>METHODS AND RESULTS: PBG can reduce obesity and metabolic inflammation in mice fed with a high-fat diet (HFD). Gut microbiota analysis reveals that PBG markedly increases the abundance of Akkermansia muciniphila, although it does not rescue HFD-induced change in the Firmicutes to Bacteroidetes ratio. It appears that PBG alters host physiology and creates an intestinal microenvironment favorable for A. muciniphila colonization. Fecal transplants from PBG-treated animals in part reduce obesity in recipient HFD-fed mice. Further, PBG is shown to upregulate expression of a set of genes related to host metabolism in microbiota-depleted mice.<br><br>CONCLUSION: The data highlight that PBG may exert its anti-obesity effects through a mirobiota-dependent (richness of specific microbiota) and -independent (modulation of host metabolism) manner. The fact that C. versicolor PBGs&#xa0;are approved oral immune boosters in cancers and chronic hepatitis with well-established safety profiles may accelerate PBG as a novel use for obesity treatment.}, }
@article {pmid30666959, year = {2019}, author = {Lavoie, S and Conway, KL and Lassen, KG and Jijon, HB and Pan, H and Chun, E and Michaud, M and Lang, JK and Gallini Comeau, CA and Dreyfuss, JM and Glickman, JN and Vlamakis, H and Ananthakrishnan, A and Kostic, A and Garrett, WS and Xavier, RJ}, title = {The Crohn's disease polymorphism, ATG16L1 T300A, alters the gut microbiota and enhances the local Th1/Th17 response.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {30666959}, issn = {2050-084X}, support = {DK097485/NH/NIH HHS/United States ; DK105653/NH/NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; F31 DK105653/DK/NIDDK NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; CA154426/NH/NIH HHS/United States ; P30 DK036836/DK/NIDDK NIH HHS/United States ; DK110499/NH/NIH HHS/United States ; R01 CA154426/CA/NCI NIH HHS/United States ; Smith Family Foundation Award for Excellence in Biomedical Research//Richard and Susan Smith Family Foundation/International ; DK092405/NH/NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; R01 DK097485/DK/NIDDK NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Autophagy-Related Proteins/*genetics ; Bacteroides ; Crohn Disease/*genetics/*microbiology ; Dysbiosis/genetics/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gene Knock-In Techniques ; Genotype ; Humans ; Immune System ; Mice ; Polymorphism, Genetic ; Risk ; Th1 Cells/*cytology/microbiology ; Th17 Cells/*cytology/microbiology ; }, abstract = {Inflammatory bowel disease (IBD) is driven by dysfunction between host genetics, the microbiota, and immune system. Knowledge gaps remain regarding how IBD genetic risk loci drive gut microbiota changes. The Crohn's disease risk allele ATG16L1 T300A results in abnormal Paneth cells due to decreased selective autophagy, increased cytokine release, and decreased intracellular bacterial clearance. To unravel the effects of ATG16L1 T300A on the microbiota and immune system, we employed a gnotobiotic model using human fecal transfers into ATG16L1 T300A knock-in mice. We observed increases in Bacteroides ovatus and Th1 and Th17 cells in ATG16L1 T300A mice. Association of altered Schaedler flora mice with B. ovatus specifically increased Th17 cells selectively in ATG16L1 T300A knock-in mice. Changes occur before disease onset, suggesting that ATG16L1 T300A contributes to dysbiosis and immune infiltration prior to disease symptoms. Our work provides insight for future studies on IBD subtypes, IBD patient treatment and diagnostics.}, }
@article {pmid30666957, year = {2019}, author = {Contijoch, EJ and Britton, GJ and Yang, C and Mogno, I and Li, Z and Ng, R and Llewellyn, SR and Hira, S and Johnson, C and Rabinowitz, KM and Barkan, R and Dotan, I and Hirten, RP and Fu, SC and Luo, Y and Yang, N and Luong, T and Labrias, PR and Lira, S and Peter, I and Grinspan, A and Clemente, JC and Kosoy, R and Kim-Schulze, S and Qin, X and Castillo, A and Hurley, A and Atreja, A and Rogers, J and Fasihuddin, F and Saliaj, M and Nolan, A and Reyes-Mercedes, P and Rodriguez, C and Aly, S and Santa-Cruz, K and Peters, L and Suárez-Fariñas, M and Huang, R and Hao, K and Zhu, J and Zhang, B and Losic, B and Irizar, H and Song, WM and Di Narzo, A and Wang, W and Cohen, BL and DiMaio, C and Greenwald, D and Itzkowitz, S and Lucas, A and Marion, J and Maser, E and Ungaro, R and Naymagon, S and Novak, J and Shah, B and Ullman, T and Rubin, P and George, J and Legnani, P and Telesco, SE and Friedman, JR and Brodmerkel, C and Plevy, S and Cho, JH and Colombel, JF and Schadt, EE and Argmann, C and Dubinsky, M and Kasarskis, A and Sands, B and Faith, JJ}, title = {Gut microbiota density influences host physiology and is shaped by host and microbial factors.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {30666957}, issn = {2050-084X}, support = {R01 CA161373/CA/NCI NIH HHS/United States ; DK112679/DK/NIDDK NIH HHS/United States ; S10 OD018522/OD/NIH HHS/United States ; GM007280/GM/NIGMS NIH HHS/United States ; P30 DK020541/DK/NIDDK NIH HHS/United States ; R01 GM108505/GM/NIGMS NIH HHS/United States ; T32 GM007280/GM/NIGMS NIH HHS/United States ; F31 DK112679/DK/NIDDK NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; R01 DK110352/DK/NIDDK NIH HHS/United States ; GM108505/GM/NIGMS NIH HHS/United States ; U19 AI118610/AI/NIAID NIH HHS/United States ; }, mesh = {Adiposity ; Adult ; Aged ; Aged, 80 and over ; Animals ; Clostridioides difficile ; Clostridium Infections/*microbiology ; Crohn Disease/*microbiology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Homeostasis ; Humans ; Ileum/microbiology ; Immune System ; Inflammatory Bowel Diseases ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; Middle Aged ; Mucous Membrane/microbiology ; Phenotype ; RNA, Ribosomal, 16S/metabolism ; Species Specificity ; Young Adult ; }, abstract = {UNLABELLED: To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn's disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.<br><br>EDITORIAL NOTE: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).}, }
@article {pmid30664879, year = {2019}, author = {Bajaj, JS and Fagan, A and Gavis, EA and Kassam, Z and Sikaroodi, M and Gillevet, PM}, title = {Long-term Outcomes of Fecal Microbiota Transplantation in Patients With Cirrhosis.}, journal = {Gastroenterology}, volume = {156}, number = {6}, pages = {1921-1923.e3}, pmid = {30664879}, issn = {1528-0012}, support = {I01 CX001076/CX/CSRD VA/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; *Cognition ; *Fecal Microbiota Transplantation ; Follow-Up Studies ; Gastrointestinal Agents/therapeutic use ; Gastrointestinal Microbiome ; Hepatic Encephalopathy/*etiology/*therapy ; *Hospitalization ; Humans ; Lactulose/therapeutic use ; Liver Cirrhosis/*complications ; Patient Selection ; Rifaximin/therapeutic use ; Stroop Test ; Time Factors ; }, }
@article {pmid30664020, year = {2019}, author = {van der Sluis, WB and Bouman, MB and Mullender, MG and Degen, MC and Savelkoul, PHM and Meijerink, WJHJ and de Boer, NKH and van Bodegraven, AA and Budding, AE}, title = {The effect of surgical fecal stream diversion of the healthy colon on the colonic microbiota.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {31}, number = {4}, pages = {451-457}, doi = {10.1097/MEG.0000000000001330}, pmid = {30664020}, issn = {1473-5687}, mesh = {Adolescent ; Adult ; Bacteria/classification/isolation &amp; purification ; Bacterial Typing Techniques ; Bacteroidetes/classification/isolation &amp; purification ; Colon/*microbiology ; Colon, Sigmoid/transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Postoperative Period ; Rectum/microbiology ; Gender-Affirming Surgery/methods ; Skin/microbiology ; Vagina/*surgery ; Young Adult ; }, abstract = {OBJECTIVES: The intestinal microbiota plays an important role in intestinal health. After colonic diversion from the fecal stream, luminal nutrients for bacteria are expected to be depleted, inducing changes in microbial composition. In this study, we describe microbial changes in the healthy colon following surgical fecal stream diversion, studied in the surgically constructed sigmoid-derived neovagina.<br><br>METHODS: At various postoperative times after sigmoid vaginoplasty, rectal, neovaginal, and skin microbial swabs were obtained for microbial analysis by interspacer profiling, a PCR-based bacterial profiling technique. Differences in bacterial profiles, in terms of bacterial abundance and phylum diversity, were assessed. Microbial dissimilarities between anatomical locations were analyzed with principal coordinate analysis and partial least squares discriminant analysis.<br><br>RESULTS: Bacterial samples were obtained from 28 patients who underwent sigmoid vaginoplasty. By principal coordinate analysis, microbial profiles of samples from the sigmoid-derived neovagina were distinctively different from rectal samples. Partial least squares discriminant analysis showed that the most discriminative species derived from the phylum Bacteroidetes. The abundance and diversity of Bacteroidetes species were reduced following fecal stream diversion compared with rectal samples (median Shannon diversity index of 2.76 vs. 2.18, P<0.01). Similar abundance of Phyla Firmicutes, Actinobacteria, Fusobacteria, Verrucomicrobia, and Proteobacteria was observed.<br><br>CONCLUSION: By analyzing the microbiome of sigmoid-derived neovaginas, we studied the effects of fecal diversion on the microbial composition of the healthy intestine. Most changes were observed in the phylum Bacteroidetes, indicating that these bacteria are likely part of the diet-dependent (butyrate-producing) colonic microbiome. Bacteria of other phyla are likely to be part of the diet-independent microbiome.}, }
@article {pmid30663928, year = {2019}, author = {Ihekweazu, FD and Fofanova, TY and Queliza, K and Nagy-Szakal, D and Stewart, CJ and Engevik, MA and Hulten, KG and Tatevian, N and Graham, DY and Versalovic, J and Petrosino, JF and Kellermayer, R}, title = {Bacteroides ovatus ATCC 8483 monotherapy is superior to traditional fecal transplant and multi-strain bacteriotherapy in a murine colitis model.}, journal = {Gut microbes}, volume = {10}, number = {4}, pages = {504-520}, pmid = {30663928}, issn = {1949-0984}, support = {T32 DK007664/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/growth &amp; development ; Bacteroides/classification/growth &amp; development/*physiology ; Colitis/chemically induced/pathology/*therapy ; Dextran Sulfate/toxicity ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Tract/microbiology/pathology ; Inflammation/prevention &amp; control ; Male ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Survival Analysis ; Treatment Outcome ; }, abstract = {Background and aims: Bacteriotherapy aimed at addressing dysbiosis may be therapeutic for Inflammatory Bowel Diseases (IBDs). We sought to determine if defined Bacteroides-based bacteriotherapy could be an effective and consistent alternative to fecal microbiota transplantation (FMT) in a murine model of IBD. Methods: We induced experimental colitis in 8- 12-week-old C57BL/6 mice using 2-3% dextran sodium sulfate. Mice were simultaneously treated by oral gavage with a triple-Bacteroides cocktail, individual Bacteroides strains, FMT using stool from healthy donor mice, or their own stool as a control. Survival, weight loss and markers of inflammation (histology, serum amyloid A, cytokine production) were correlated to 16S rRNA gene profiling of fecal and mucosal microbiomes. Results: Triple-Bacteroides combination therapy was more protective against weight loss and mortality than traditional FMT therapy. B. ovatus ATCC8483 was more effective than any individual strain, or a combination of strains, in preventing weight loss, decreasing histological damage, dampening inflammatory response, and stimulating epithelial recovery. Irrespective of the treatment group, overall Bacteroides abundance associated with treatment success and decreased cytokine production while the presence of Akkermansia correlated with treatment failure. However, the therapeutic benefit associated with high Bacteroides abundance was negated in the presence of Streptococcus. Conclusions: Bacteroides ovatus monotherapy was more consistent and effective than traditional FMT at ameliorating colitis and stimulating epithelial recovery in a murine model of IBD. Given the tolerability of Bacteroides ovatus ATCC 8483 in an active, on-going human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.}, }
@article {pmid30662590, year = {2018}, author = {Xiao, J and Peng, Z and Liao, Y and Sun, H and Chen, W and Chen, X and Wei, Z and Yang, C and Nüssler, AK and Liu, J and Yang, W}, title = {Organ transplantation and gut microbiota: current reviews and future challenges.}, journal = {American journal of translational research}, volume = {10}, number = {11}, pages = {3330-3344}, pmid = {30662590}, issn = {1943-8141}, abstract = {Organ transplantation is often the only effective treatment for patients with end-stage diseases, such as heart, liver, kidney and small bowel failure and is carried out frequently worldwide. Still the post-transplantation complications remain health- and life-threatening outcome that needed to be resolved. With the rapid development of molecular technologies in recent years, more and more researchers realize that the gut microbiota may play a critical role in human diseases. The intestinal microbiome has been proved to provide a lot of functions to the host, such as digesting food, modulating metabolism, promoting angiogenesis and regulating the immune system. Several studies have investigated the alteration of intestinal microbiota in post-transplantation patients and observed significant changes in the intestinal microbiome compared to the pre-transplant condition. Due to the abovementioned features that the gut microbiota may be used in the prognosis of clinical outcome of organ transplantation. In addition, the FMT (fecal microbiota transplantation), probiotics and prebiotics as the newest therapy methods, effectiveness of which has been verified in some diseases, such as Clostridium difficile infection, inflammatory bowel disease and other chronic disorders, might be used as the prognosis tool in organ transplantation as well. The purpose of this present review is to elucidate the relationship between gut microbiota and organ transplantation as well as the potential use of new therapies like fecal microbiota transplantation, probiotic and prebiotic administration after the transplantation, and provide some ideas for future researches in field of organ transplantation.}, }
@article {pmid30661694, year = {2019}, author = {Hamilton, K and Crowe, T and Testro, A}, title = {High amylase resistant starch to decrease stool output in people with short bowel syndrome: A pilot trial.}, journal = {Clinical nutrition ESPEN}, volume = {29}, number = {}, pages = {242-244}, doi = {10.1016/j.clnesp.2018.10.006}, pmid = {30661694}, issn = {2405-4577}, mesh = {Amylases/*metabolism ; Cross-Over Studies ; Diarrhea/diet therapy ; Diet ; Fatty Acids ; Feces/*chemistry ; Female ; Humans ; Intestines ; Male ; Middle Aged ; Nutritional Status ; Pilot Projects ; Short Bowel Syndrome/*diet therapy/*physiopathology ; Starch/*metabolism ; }, abstract = {UNLABELLED: Short bowel syndrome (SBS) is defined as having less than 200 cm of functional small bowel. Malabsorptive diarrhoea and dehydration are difficult to manage despite medical therapy and dietary manipulations. Evidence shows that supplementing the diet with High Amylase Resistant Starch (HARS) can reduce diarrhoea from a number of causes including gastroenteritis. It is hypothesised HARS will decrease stool output via the production of short chain fatty acids and the resultant increased water reabsorption. This study aimed to determine if the addition of HARS can reduce diarrhoea in patients with SBS.<br><br>METHODS: Patients with SBS with colon in continuity were recruited from the intestinal rehabilitation clinic at Austin Health. The study was a 2 week crossover trial. Each participant completed the control and the intervention (addition of 50&#xa0;g HARS to usual diet). Total daily stool weight and number of bowel actions per day were compared between groups using paired t-tests.<br><br>RESULTS: Eight adults (58% male, mean age 55.7&#xa0;yrs) were recruited. Five participants completed the trial. Total daily stool weight was reduced in all participants when consuming HARS. Mean daily stool output was significantly decreased 1049&#xa0;&#xb1;&#xa0;519&#xa0;g/d to 804&#xa0;&#xb1;&#xa0;585&#xa0;g/d (p&#xa0;=&#xa0;0.023). Number of bowel actions per day showed a trend to reduction.<br><br>CONCLUSION: This study gives some support to the hypothesis that the addition of HARS into the diet of patients with short bowel syndrome reduces stool output. Longer trials are required to confirm the effect on nutritional/hydration status.}, }
@article {pmid30661163, year = {2019}, author = {Knox, NC and Forbes, JD and Van Domselaar, G and Bernstein, CN}, title = {The Gut Microbiome as a Target for IBD Treatment: Are We There Yet?.}, journal = {Current treatment options in gastroenterology}, volume = {17}, number = {1}, pages = {115-126}, pmid = {30661163}, issn = {1092-8472}, abstract = {PURPOSE OF REVIEW: This review aims to highlight recent research on the gut microbiome in IBD and the application of microbiome-modulating therapies for the treatment of IBD including the use of the microbiome as an indicator for disease severity and treatment response.<br><br>RECENT FINDINGS: Despite the high number of gut microbiome studies and emerging evidence supporting the gut microbiome's involvement in disease pathogenesis, no single microorganism has been identified as a pathogenic agent in IBD. Retrospective studies and meta-analyses on antibiotic use in ulcerative colitis and Crohn's disease and long-term outcomes are conflicting. Similarly, the use of probiotics for the treatment of IBD remains inconclusive; however, some encouraging results are emerging as microbial concoctions are optimized to include beneficial bacterial strains. Fecal microbial transplantation (FMT) is currently emerging as one of the more promising microbiome-modulating IBD therapies. FMT studies in ulcerative colitis have shown improved remission rates compared to placebo; however, relatively small study sample sizes and varied treatment methods, limit definitive conclusions. With clear evidence of an IBD gut dysbiosis, novel therapies to treat and prevent disease relapse will undoubtedly require a microbiome-modulating approach. The complexity and variability of IBD disease pathogenesis (disease phenotype, gut microbiome, host genetic susceptibility, and environmental factors) will likely require a personalized and multidimensional treatment approach where microbiome-modulating therapy is coupled with other therapies to target other IBD disease components.}, }
@article {pmid30658733, year = {2019}, author = {Gustot, T and Jalan, R}, title = {Acute-on-chronic liver failure in patients with alcohol-related liver disease.}, journal = {Journal of hepatology}, volume = {70}, number = {2}, pages = {319-327}, doi = {10.1016/j.jhep.2018.12.008}, pmid = {30658733}, issn = {1600-0641}, mesh = {Acute-On-Chronic Liver Failure/drug therapy/*epidemiology/*etiology/physiopathology ; Adrenal Cortex Hormones/therapeutic use ; Alcohol Drinking/*adverse effects ; Bacterial Infections/*complications ; Cytokines/metabolism ; Fecal Microbiota Transplantation ; Female ; Humans ; Inflammation/immunology ; Leukocytes/immunology ; Liver Diseases, Alcoholic/*complications ; Liver Transplantation ; Macrophages/immunology ; Male ; Prognosis ; }, abstract = {The spectrum of alcohol-related liver diseases (ALD) includes steatosis, steatohepatitis, progressive liver fibrosis, and cirrhosis. Acute-on-chronic liver failure (ACLF) is a recently defined entity that occurs in patients with chronic liver diseases and is characterised by acute decompensation, organ failures and a high risk of short-term mortality. Active alcohol consumption, alcoholic hepatitis and bacterial infections are the most frequent events precipitating the development of ACLF in the context of ALD (ALD-ACLF). The specific management of this entity remains unknown and the place of salvage liver transplantation controversial. This overview details the current knowledge on specific aspects of epidemiology, pathophysiology, prognosis and management of ALD-ACLF.}, }
@article {pmid30658731, year = {2019}, author = {Singal, AK and Shah, VH}, title = {Current trials and novel therapeutic targets for alcoholic hepatitis.}, journal = {Journal of hepatology}, volume = {70}, number = {2}, pages = {305-313}, doi = {10.1016/j.jhep.2018.10.026}, pmid = {30658731}, issn = {1600-0641}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; Antioxidants/therapeutic use ; Clinical Trials as Topic ; Drug Therapy, Combination ; Ethanol/pharmacology ; Fecal Microbiota Transplantation ; Gastrointestinal Agents/therapeutic use ; Gastrointestinal Microbiome/drug effects ; Hepatitis, Alcoholic/*drug therapy/*physiopathology ; Humans ; Tumor Necrosis Factor Inhibitors/therapeutic use ; Zinc/therapeutic use ; }, abstract = {Alcoholic hepatitis is a clinical syndrome in which patients present with acute-on-chronic liver failure and a high risk of short-term mortality. The current treatment of alcoholic hepatitis is suboptimal. Results recently published from the STOPAH study have improved our understanding of how best to design clinical trials for this condition. Although emerging data on liver transplantation for patients with alcoholic hepatitis are encouraging, less than 2% of these patients qualify. Clearly, there is an unmet need for novel treatments to improve the survival of these patients. Changes in the gut microbiota, inflammatory and cytokine signalling, oxidative stress and mitochondrial dysfunction, and abnormalities in the hepatic regenerative capacity alone or in combination contribute to the pathology of alcoholic hepatitis. In this chapter, we will describe the novel therapeutic agents targeting various pathways in the pathophysiology of alcoholic hepatitis. Specifically, we will describe the ongoing clinical trials in which some of these agents are being studied.}, }
@article {pmid30658727, year = {2019}, author = {Sarin, SK and Pande, A and Schnabl, B}, title = {Microbiome as a therapeutic target in alcohol-related liver disease.}, journal = {Journal of hepatology}, volume = {70}, number = {2}, pages = {260-272}, doi = {10.1016/j.jhep.2018.10.019}, pmid = {30658727}, issn = {1600-0641}, support = {R01 AA020703/AA/NIAAA NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; U01 AA021856/AA/NIAAA NIH HHS/United States ; U01 AA026939/AA/NIAAA NIH HHS/United States ; }, mesh = {Adrenal Cortex Hormones/therapeutic use ; Animals ; Anti-Bacterial Agents/therapeutic use ; Dysbiosis/chemically induced/microbiology ; Ethanol/*pharmacology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Humans ; Liver Diseases, Alcoholic/*diet therapy/*drug therapy/metabolism/microbiology ; Metabolome/drug effects ; Probiotics/therapeutic use ; }, abstract = {Alcohol-related liver disease is associated with significant changes in gut microbial composition. The transmissibility of ethanol-induced liver disease has been demonstrated using faecal microbiota transfer in preclinical models. This technique has also led to improved survival in patients with severe alcoholic hepatitis, suggesting that changes in the composition and function of the gut microbiota are causatively linked to alcohol-related liver disease. A major mechanism by which gut microbiota influence the development of alcohol-related liver disease is through a leaky intestinal barrier. This permits translocation of viable bacteria and microbial products to the liver, where they induce and promote inflammation, as well as contribute to hepatocyte death and the fibrotic response. In addition, gut dysbiosis is associated with changes in the metabolic function of the intestinal microbiota, bile acid composition and circulation, immune dysregulation during onset and progression of alcohol-related liver disease. Findings from preclinical and human studies will be used to demonstrate how alcohol causes intestinal pathology and contributes to alcohol-related liver disease and how the latter is self-perpetuating. Additionally, we summarise the effects of untargeted treatment approaches on the gut microbiota, such as diet, probiotics, antibiotics and faecal microbial transplantation in alcohol-related liver disease. We further discuss how targeted approaches can restore intestinal homeostasis and improve alcohol-related liver disease. These approaches are likely to add to the therapeutic options for alcohol-related liver disease independently or in conjunction with steroids.}, }
@article {pmid30658519, year = {2019}, author = {Milosevic, I and Vujovic, A and Barac, A and Djelic, M and Korac, M and Radovanovic Spurnic, A and Gmizic, I and Stevanovic, O and Djordjevic, V and Lekic, N and Russo, E and Amedei, A}, title = {Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature.}, journal = {International journal of molecular sciences}, volume = {20}, number = {2}, pages = {}, pmid = {30658519}, issn = {1422-0067}, mesh = {Animals ; *Disease Susceptibility ; Dysbiosis ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/immunology/*metabolism/*microbiology ; Humans ; Liver/immunology/*metabolism/pathology ; Liver Diseases/*etiology/*metabolism/pathology/therapy ; Prebiotics ; Probiotics ; Symbiosis ; }, abstract = {The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called "the new virtual metabolic organ", makes axis with a number of extraintestinal organs, such as kidneys, brain, cardiovascular, and the bone system. The gut-liver axis has attracted greater attention in recent years. GM communication is bi-directional and involves endocrine and immunological mechanisms. In this way, gut-dysbiosis and composition of "ancient" microbiota could be linked to pathogenesis of numerous chronic liver diseases such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), development of liver cirrhosis, and hepatocellular carcinoma (HCC). In this paper, we discuss the current evidence supporting a GM role in the management of different chronic liver diseases and potential new therapeutic GM targets, like fecal transplantation, antibiotics, probiotics, prebiotics, and symbiotics. We conclude that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases. This could have a positive impact on future therapeutic strategies.}, }
@article {pmid30655087, year = {2019}, author = {Markowski, MC and Boorjian, SA and Burton, JP and Hahn, NM and Ingersoll, MA and Maleki Vareki, S and Pal, SK and Sfanos, KS}, title = {The Microbiome and Genitourinary Cancer: A Collaborative Review.}, journal = {European urology}, volume = {75}, number = {4}, pages = {637-646}, pmid = {30655087}, issn = {1873-7560}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Genitalia/*microbiology/pathology ; Host-Pathogen Interactions ; Humans ; Kidney Neoplasms/*microbiology/pathology/therapy/urine ; Male ; *Microbiota ; Prognosis ; Prostatic Neoplasms/*microbiology/pathology/therapy/urine ; Risk Factors ; Testicular Neoplasms/*microbiology/pathology/therapy/urine ; Urinary Bladder Neoplasms/*microbiology/pathology/therapy/urine ; Urinary Tract/*microbiology/pathology ; Urine/microbiology ; }, abstract = {CONTEXT: The recent discovery of the existence of a human genitourinary microbiome has led to the investigation of its role in mediating the pathogenesis of genitourinary malignancies, including bladder, kidney, and prostate cancers. Furthermore, although it is largely recognized that members of the gastrointestinal microbiota are actively involved in drug metabolism, new studies demonstrate additional roles and the potential necessity of the gastrointestinal microbiota in dictating cancer treatment response.<br><br>OBJECTIVE: To summarize the current evidence of a mechanistic role for the genitourinary and gastrointestinal microbiome in genitourinary cancer initiation and treatment response.<br><br>EVIDENCE ACQUISITION: We conducted a literature search up to October 2018. Search terms included microbiome, microbiota, urinary microbiome, bladder cancer, urothelial carcinoma, renal cell carcinoma, kidney cancer, testicular cancer, and prostate cancer.<br><br>EVIDENCE SYNTHESIS: There is preliminary evidence to implicate the members of the genitourinary microbiota as causative factors or cofactors in genitourinary malignancy. Likewise, the current evidence for gastrointestinal microbes in dictating cancer treatment response is mainly correlative; however, we provide examples where therapeutic agents used for the treatment of genitourinary cancers are affected by the human-associated microbiota, or vice versa. Clinical trials, such as fecal microbiota transplant to increase the efficacy of immunotherapy, are currently underway.<br><br>CONCLUSIONS: The role of the microbiome in genitourinary cancer is an emerging field that merits further studies. Translating microbiome research into clinical action will require incorporation of microbiome surveillance into ongoing and future clinical trials as well as expansion of studies to include metagenomic sequencing and metabolomics.<br><br>PATIENT SUMMARY: This review covers recent evidence that microbial populations that reside in the genitourinary tract-and were previously not known to exist-may influence the development of genitourinary malignancies including bladder, kidney, and prostate cancers. Furthermore, microbial populations that exist at sites outside of the genitourinary tract, such as those that reside in our gut, may influence cancer development and/or treatment response.}, }
@article {pmid30655033, year = {2019}, author = {Weng, MT and Chiu, YT and Wei, PY and Chiang, CW and Fang, HL and Wei, SC}, title = {Microbiota and gastrointestinal cancer.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118 Suppl 1}, number = {}, pages = {S32-S41}, doi = {10.1016/j.jfma.2019.01.002}, pmid = {30655033}, issn = {0929-6646}, mesh = {Carcinogenesis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Neoplasms/*microbiology/*prevention &amp; control ; Gastrointestinal Tract/*microbiology ; Humans ; Risk Factors ; Synbiotics/administration &amp; dosage ; }, abstract = {Gut microbiota plays important roles in many diseases, including cancer. It may promote carcinogenesis by inducing oxidative stress, genotoxicity, host immune response disturbance, and chronic inflammation. Colorectal cancer, hepatocellular carcinoma, and gastric cancer are the major gastrointestinal tract cancers in Taiwan. The microbiota detected in patients with tubular adenoma and villous/tubulovillous polyps is different from that in healthy controls and patients with hyperplastic polyps. Normalization of the microbiota is observed in patients after colorectal cancer treatment. Furthermore, the liver is exposed to microbiota-associated molecular patterns (MAMPs), bacterial metabolites, and toxins, as it is anatomically connected to the gut via the portal vein. Patients with cirrhosis have significantly higher plasma endotoxin levels than healthy controls. Helicobacter pylori is a well-established risk factor for gastric cancer. Some nitrosating bacteria convert nitrogen compounds in gastric fluid to potentially carcinogenic N-nitroso compounds, which also contribute to gastric cancer development. Growing evidence demonstrates that gut microbiota promotes carcinogenesis. In this review, we discuss the mechanisms and types of microbiota changes involved in these gastrointestinal cancers and the future treatment choices.}, }
@article {pmid30651577, year = {2019}, author = {Goethel, A and Turpin, W and Rouquier, S and Zanello, G and Robertson, SJ and Streutker, CJ and Philpott, DJ and Croitoru, K}, title = {Nod2 influences microbial resilience and susceptibility to colitis following antibiotic exposure.}, journal = {Mucosal immunology}, volume = {12}, number = {3}, pages = {720-732}, pmid = {30651577}, issn = {1935-3456}, support = {THC-13523//CIHR/Canada ; }, mesh = {Amoxicillin/administration &amp; dosage/*adverse effects ; Animals ; Animals, Newborn ; Anti-Bacterial Agents/administration &amp; dosage/*adverse effects ; Colitis/genetics/*metabolism ; Disease Models, Animal ; Disease Susceptibility ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects/physiology ; Gene-Environment Interaction ; Humans ; Inflammatory Bowel Diseases/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nod2 Signaling Adaptor Protein/genetics/*metabolism ; Risk ; }, abstract = {Inflammatory bowel disease (IBD) etiology involves genetic susceptibility, environmental triggers, and the gut microbiome. Antibiotic exposure is associated with IBD, both in early life and adulthood. Here, we investigated whether Nod2-deficiency influenced response of the gut microbiota to antibiotics and subsequent colitis susceptibility. Wild-type and Nod2[-/-] littermate mice were treated with amoxicillin as adults or neonates, and fecal samples were collected for 16S rRNA sequencing. Five weeks after antibiotic exposure, dextran sulfate sodium (DSS) colitis was induced. Antibiotic treatment altered the microbiota of adult WT and Nod2[-/-] mice, but recovery was delayed in Nod2[-/-] mice. Neonatal antibiotic treatment significantly changed the microbiota at weaning in WT and Nod2[-/-] littermates; however, Nod2[-/-] mice maintained reduced microbial diversity 14 days after cessation of antibiotics. Although treatment of adult mice did not influence susceptibility to colitis, neonatally treated Nod2[-/-] mice developed a more severe colitis. Moreover, the colitis phenotype was transferable through fecal transplantation into germ-free Nod2[-/-] recipients, and was associated with changes in intestinal T cells and the cytokine milieu following inflammation. These data demonstrate that neonatal antibiotic exposure has long-lasting influence on the microbiota and mucosal immunity, and may explain how NOD2 contributes to the risk of intestinal inflammation.}, }
@article {pmid30648128, year = {2019}, author = {Torres Soto, M and Hammond, S and Elshaboury, RH and Johnson, J and Hohmann, EL}, title = {Recurrent Relatively Resistant Salmonella infantis Infection in 2 Immunocompromised Hosts Cleared With Prolonged Antibiotics and Fecal Microbiota Transplantation.}, journal = {Open forum infectious diseases}, volume = {6}, number = {1}, pages = {ofy334}, pmid = {30648128}, issn = {2328-8957}, abstract = {Two immunocompromised patients with relapsing gastrointestinal infection with relatively resistant Salmonella infantis were cured with prolonged ertapenem followed by encapsulated fecal transplant.}, }
@article {pmid30647011, year = {2019}, author = {The Lancet Gastroenterology Hepatology, }, title = {Probiotics: elixir or empty promise?.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {4}, number = {2}, pages = {81}, doi = {10.1016/S2468-1253(18)30415-1}, pmid = {30647011}, issn = {2468-1253}, mesh = {Clinical Trials as Topic ; Fecal Microbiota Transplantation ; Gastroenteritis/*microbiology ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Lactobacillus helveticus/pathogenicity ; Lacticaseibacillus rhamnosus/pathogenicity ; North America/epidemiology ; Probiotics/adverse effects/economics/*therapeutic use ; }, }
@article {pmid30646487, year = {2019}, author = {Widmann, B and Galata, C and Warschkow, R and Beutner, U and Ögredici, &#xd6; and Hetzer, FH and Schmied, BM and Post, S and Marti, L}, title = {Success and Complication Rates After Sacral Neuromodulation for Fecal Incontinence and Constipation: A Single-center Follow-up Study.}, journal = {Journal of neurogastroenterology and motility}, volume = {25}, number = {1}, pages = {159-170}, pmid = {30646487}, issn = {2093-0879}, abstract = {BACKGROUND/AIMS: The aim of this study was to evaluate the sustainability of sacral neuromodulation (SNM) success in patients with fecal incontinence (FI) and/or constipation.<br><br>METHODS: This is a retrospective analysis of a prospective database of patients who received SNM therapy for FI and/or constipation between 2006 and 2015. Success rates, complications and reintervention rates were assessed after up to 10 years of follow-up.<br><br>RESULTS: Electrodes for test stimulation were implanted in 101 patients, of whom 79 (78.2%) received permanent stimulation. The mean follow-up was 4.4 &#xb1; 3.0 years. At the end of follow-up, 57 patients (72.2%) were still receiving SNM. The 5-year success rate for FI and isolated constipation was 88.2% (95% confidence interval [CI], 80.1-97.0%) and 31.2% (95% CI, 10.2-95.5%), respectively (P &#xff1c; 0.001). In patients with FI, involuntary evacuations per week decreased &#xff1e; 50% in 76.1% of patients (95% CI, 67.6-86.2%) after 5 years. A lead position at S3 was associated with an improved outcome (P = 0.04). Battery exchange was necessary in 23 patients (29.1%), with a median battery life of 6.2 years. Reinterventions due to complications were necessary in 24 patients (30.4%). For these patients, the 5-year success rate was 89.0% (95% CI, 75.3-100.0%) compared to 78.4% (95% CI, 67.2-91.4%) for patients without reintervention.<br><br>CONCLUSIONS: SNM offers an effective sustainable treatment for FI. For constipation, lasting success of SNM is limited and is thus not recommended. Reinterventions are necessary but do not impede treatment success.}, }
@article {pmid30644982, year = {2019}, author = {Costello, SP and Hughes, PA and Waters, O and Bryant, RV and Vincent, AD and Blatchford, P and Katsikeros, R and Makanyanga, J and Campaniello, MA and Mavrangelos, C and Rosewarne, CP and Bickley, C and Peters, C and Schoeman, MN and Conlon, MA and Roberts-Thomson, IC and Andrews, JM}, title = {Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial.}, journal = {JAMA}, volume = {321}, number = {2}, pages = {156-164}, pmid = {30644982}, issn = {1538-3598}, mesh = {Adult ; Anaerobiosis ; Colitis, Ulcerative/*therapy ; Colonoscopy ; Double-Blind Method ; Enema ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Metabolome ; Middle Aged ; Remission Induction/methods ; Surveys and Questionnaires ; Transplantation, Autologous ; Transplantation, Homologous ; Young Adult ; }, abstract = {IMPORTANCE: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity.<br><br>OBJECTIVE: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool.<br><br>A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017.<br><br>INTERVENTIONS: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n&#x2009;=&#x2009;38) or autologous FMT (n&#x2009;=&#x2009;35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of &#x2264;2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0&#x2009;=&#x2009;no disease and 12&#x2009;=&#x2009;most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events.<br><br>RESULTS: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P&#x2009;=&#x2009;.03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group.<br><br>CONCLUSIONS AND RELEVANCE: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety.<br><br>TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12613000236796.}, }
@article {pmid30644970, year = {2019}, author = {Kelly, CR and Ananthakrishnan, AN}, title = {Manipulating the Microbiome With Fecal Transplantation to Treat Ulcerative Colitis.}, journal = {JAMA}, volume = {321}, number = {2}, pages = {151-152}, doi = {10.1001/jama.2018.20397}, pmid = {30644970}, issn = {1538-3598}, mesh = {*Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Microbiota ; }, }
@article {pmid30643841, year = {2018}, author = {Tran, V and Phan, J and Nulsen, B and Huang, L and Kaneshiro, M and Weiss, G and Ho, W and Sack, J and Ha, C and Uslan, D and Sauk, JS}, title = {Severe Ileocolonic Crohn's Disease Flare Associated with Fecal Microbiota Transplantation Requiring Diverting Ileostomy.}, journal = {ACG case reports journal}, volume = {5}, number = {}, pages = {e97}, pmid = {30643841}, issn = {2326-3253}, abstract = {Patients with inflammatory bowel disease (IBD) are at increased risk of developing Clostridium difficile infection (CDI). Fecal microbiota transplantation (FMT) is an effective therapy with a high success rate in preventing recurrent CDI. However, patients with IBD have decreased response to FMT for recurrent CDI, with several reports also suggesting potential IBD flare post-FMT. We present a case of mild ileocolonic Crohn's disease in a patient treated with FMT for recurrent CDI who subsequently developed severe steroid-refractory flare requiring surgical intervention 1 week post-FMT. Greater understanding of risk factors associated with post-FMT IBD flare is indicated.}, }
@article {pmid30643289, year = {2019}, author = {Feehley, T and Plunkett, CH and Bao, R and Choi Hong, SM and Culleen, E and Belda-Ferre, P and Campbell, E and Aitoro, R and Nocerino, R and Paparo, L and Andrade, J and Antonopoulos, DA and Berni Canani, R and Nagler, CR}, title = {Healthy infants harbor intestinal bacteria that protect against food allergy.}, journal = {Nature medicine}, volume = {25}, number = {3}, pages = {448-453}, pmid = {30643289}, issn = {1546-170X}, support = {UL1 TR000430/TR/NCATS NIH HHS/United States ; P30 DK042086/DK/NIDDK NIH HHS/United States ; P30 CA014599/CA/NCI NIH HHS/United States ; R56 AI134923/AI/NIAID NIH HHS/United States ; R25 GM109439/GM/NIGMS NIH HHS/United States ; T32 AI007090/AI/NIAID NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; R01 AI106302/AI/NIAID NIH HHS/United States ; }, mesh = {Anaphylaxis/*microbiology ; Animals ; Clostridiales/genetics ; *Fecal Microbiota Transplantation ; Female ; Food Hypersensitivity/microbiology ; Gastrointestinal Microbiome/*genetics ; Germ-Free Life ; Healthy Volunteers ; Humans ; Ileum/microbiology ; Infant ; Male ; Mice ; Milk Hypersensitivity/*microbiology ; }, abstract = {There has been a striking generational increase in life-threatening food allergies in Westernized societies[1,2]. One hypothesis to explain this rising prevalence is that twenty-first century lifestyle practices, including misuse of antibiotics, dietary changes, and higher rates of Caesarean birth and formula feeding have altered intestinal bacterial communities; early-life alterations may be particularly detrimental[3,4]. To better understand how commensal bacteria regulate food allergy in humans, we colonized germ-free mice with feces from healthy or cow's milk allergic (CMA) infants[5]. We found that germ-free mice colonized with bacteria from healthy, but not CMA, infants were protected against anaphylactic responses to a cow's milk allergen. Differences in bacterial composition separated the healthy and CMA populations in both the human donors and the colonized mice. Healthy and CMA colonized mice also exhibited unique transcriptome signatures in the ileal epithelium. Correlation of ileal bacteria with genes upregulated in the ileum of healthy or CMA colonized mice identified a clostridial species, Anaerostipes caccae, that protected against an allergic response to food. Our findings demonstrate that intestinal bacteria are critical for regulating allergic responses to dietary antigens and suggest that interventions that modulate bacterial communities may be therapeutically relevant for food allergy.}, }
@article {pmid30643227, year = {2019}, author = {Bajaj, JS}, title = {Alcohol, liver disease and the gut microbiota.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {16}, number = {4}, pages = {235-246}, doi = {10.1038/s41575-018-0099-1}, pmid = {30643227}, issn = {1759-5053}, mesh = {Anti-Bacterial Agents/therapeutic use ; Dysbiosis/*complications/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Liver Diseases, Alcoholic/*microbiology/physiopathology/psychology/therapy ; Probiotics ; }, abstract = {Alcoholic liver disease, which ranges from mild disease to alcoholic hepatitis and cirrhosis, is a leading cause of morbidity and mortality worldwide. Alcohol intake can lead to changes in gut microbiota composition, even before liver disease development. These alterations worsen with advancing disease and could be complicit in disease progression. Microbial function, especially related to bile acid metabolism, can modulate alcohol-associated injury even in the presence of cirrhosis and alcoholic hepatitis. Microbiota changes might also alter brain function, and the gut-brain axis might be a potential target to reduce alcoholic relapse risk. Gut microbiota manipulation including probiotics, faecal microbial transplant and antibiotics has been studied in alcoholic liver disease with varying success. Further investigation of the modulation of the gut-liver axis is relevant, as most of these patients are not candidates for liver transplantation. This Review focuses on clinical studies involving the gut microbiota in patients with alcoholic liver disease across the spectrum from alcoholic fatty liver to cirrhosis and alcoholic hepatitis. Specific alterations in the gut-liver-brain axis that are complicit in the interactions between the gut microbiota and alcohol addiction are also reviewed.}, }
@article {pmid30642269, year = {2019}, author = {Zhang, K and Beckett, P and Abouanaser, S and Stankus, V and Lee, C and Smieja, M}, title = {Prolonged oral vancomycin for secondary prophylaxis of relapsing Clostridium difficile infection.}, journal = {BMC infectious diseases}, volume = {19}, number = {1}, pages = {51}, pmid = {30642269}, issn = {1471-2334}, mesh = {Administration, Oral ; Aged ; Aged, 80 and over ; Antibiotic Prophylaxis/*methods ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/*prevention &amp; control ; Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; Vancomycin/*administration &amp; dosage/*therapeutic use ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is an important cause of diarrhea and continues to be a major burden within healthcare institutions and in the community. For a small subset of patients with frequently relapsing CDI who do not have access to fecal microbiota transplantation (FMT), or fail FMT, there are no clear treatment recommendations. We review our experience with prolonged oral vancomycin for secondary prophylaxis of relapsing CDI.<br><br>METHODS: We performed a retrospective chart review of cases from the C. difficile consultation service at our institution since 2013. The service had three primary physicians providing consultations and performing over 1000 FMTs over the five-year period. Patients with relapsing CDI who were not candidates for FMT, refused, or relapsed after FMT were treated with vancomycin, followed by long-term oral vancomycin at a dose of 125&#x2009;mg once daily.<br><br>RESULTS: Twenty patients received at least 8 weeks of once-daily oral vancomycin for prophylaxis of relapsing CDI. Patients had a median age of 80&#x2009;years, and experienced a median of four episodes of CDI prior to long-term vancomycin. Most were female and 75% had received FMT. Only a single case of C. difficile relapse occurred while on long-term vancomycin during 200 patient-months of follow-up. Amongst those who stopped long-term vancomycin, 31% relapsed within 6&#x2009;weeks. No adverse events were observed.<br><br>CONCLUSIONS: For elderly patients with frequently relapsing C. difficile, prolonged vancomycin once daily at a dose of 125&#x2009;mg orally was effective in preventing further relapse. Vancomycin secondary prophylaxis may be considered in patients who have failed FMT, or in cases where FMT is not available.}, }
@article {pmid30639376, year = {2019}, author = {Felizardo, RJF and Watanabe, IKM and Dardi, P and Rossoni, LV and Câmara, NOS}, title = {The interplay among gut microbiota, hypertension and kidney diseases: The role of short-chain fatty acids.}, journal = {Pharmacological research}, volume = {141}, number = {}, pages = {366-377}, doi = {10.1016/j.phrs.2019.01.019}, pmid = {30639376}, issn = {1096-1186}, mesh = {Animals ; Dysbiosis/*complications/metabolism/therapy ; Fatty Acids, Volatile/*metabolism/therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Hypertension/*etiology/metabolism/therapy ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage/therapeutic use ; Renal Insufficiency, Chronic/*etiology/metabolism/therapy ; }, abstract = {The bacteria community living in the gut maintains a symbiotic relationship with the host and its unbalance has been associated with progression of a wide range of intestinal and extra intestinal conditions. Hypertension and chronic kidney disease (CKD) are closely associated diseases with high incidence rates all over the world. Increasing data have supported the involvement of gut microbiome in the blood pressure regulation and the impairment of CKD prognosis. In hypertension, the reduced number of short-chain fatty acids (SCFAs) producing bacteria is associated with modifications in gut environment, involving reduction of the hypoxic gut profile and worsening of the microbial balance, leading to a loss of epithelial barrier integrity, development of gut inflammation and the reduction of SCFAs plasma levels. These modifications compromise the blood pressure regulation and, as a consequence, favor the end organ damage, also affecting the kidneys. In CKD, impaired renal function leads to accumulation of high levels of uremic toxins that reach the intestine and cause alterations in bacteria composition and fecal metabolite profile, inducing a positive feedback that allows translocation of endotoxins into the bloodstream, which enhances local kidney inflammation and exacerbate kidney injury, compromising even more CKD prognosis. In line with these data, the use of prebiotics, probiotics and fecal microbiota transplantation are becoming efficient therapies to improve the gut dysbiosis aiming hypertension and CKD treatment. This review describes how changes in gut microbiota composition can affect the development of hypertension and the progression of kidney diseases, highlighting the importance of the gut microbial composition uncovering to improve human health maintenance and, especially, for the development of new alternative therapies.}, }
@article {pmid30638679, year = {2019}, author = {Langan, D and Kim, EY and Moudgil, KD}, title = {Modulation of autoimmune arthritis by environmental 'hygiene' and commensal microbiota.}, journal = {Cellular immunology}, volume = {339}, number = {}, pages = {59-67}, pmid = {30638679}, issn = {1090-2163}, support = {I01 BX002424/BX/BLRD VA/United States ; R01 AT004321/AT/NCCIH NIH HHS/United States ; }, mesh = {Animals ; Arthritis, Rheumatoid/*immunology ; Autoimmune Diseases/*immunology ; Autoimmunity/*immunology ; Dysbiosis/immunology ; Gastrointestinal Microbiome/*immunology ; Humans ; T-Lymphocyte Subsets/immunology ; }, abstract = {Observations in patients with autoimmune diseases and studies in animal models of autoimmunity have revealed that external environmental factors including exposure to microbes and the state of the host gut microbiota can influence susceptibility to autoimmunity and subsequent disease development. Mechanisms underlying these outcomes continue to be elucidated. These include deviation of the cytokine response and imbalance between pathogenic versus regulatory T cell subsets. Furthermore, specific commensal organisms are associated with enhanced severity of arthritis in susceptible individuals, while exposure to certain microbes or helminths can afford protection against this disease. In addition, the role of metabolites (e.g., short-chain fatty acids, tryptophan catabolites), produced either by the microbes themselves or from their action on dietary products, in modulation of arthritis is increasingly being realized. In this context, re-setting of the microbial dysbiosis in RA using prebiotics, probiotics, or fecal microbial transplant is emerging as a promising approach for the prevention and treatment of arthritis. It is hoped that advances in defining the interplay between gut microbiota, dietary products, and bioactive metabolites would help in the development of therapeutic regimen customized for the needs of individual patients in the near future.}, }
@article {pmid30637223, year = {2018}, author = {Philips, CA and Augustine, P and Phadke, N}, title = {Healthy Donor Fecal Microbiota Transplantation for Recurrent Bacterial Cholangitis in Primary Sclerosing Cholangitis - A Single Case Report.}, journal = {Journal of clinical and translational hepatology}, volume = {6}, number = {4}, pages = {438-441}, pmid = {30637223}, issn = {2225-0719}, abstract = {Recurrent acute bacterial cholangitis is a unique indication for liver transplantation in primary sclerosing cholangitis. We present the first report on utility of healthy donor fecal transplantation for management of recurrent acute bacterial cholangitis in a primary sclerosing cholangitis patient. We demonstrate the striking liver biochemistry, bile acid and bacterial community changes following intestinal microbiota transplantation associated with amelioration of recurrent cholangitis.}, }
@article {pmid30634997, year = {2019}, author = {Barbut, F and Galperine, T and Vanhems, P and Le Monnier, A and Durand-Gasselin, B and Canis, F and Jeanbat, V and Duburcq, A and Alami, S and Bensoussan, C and Fagnani, F}, title = {Quality of life and utility decrement associated with Clostridium difficile infection in a French hospital setting.}, journal = {Health and quality of life outcomes}, volume = {17}, number = {1}, pages = {6}, pmid = {30634997}, issn = {1477-7525}, mesh = {Aged ; *Clostridium Infections ; Female ; France ; Humans ; Male ; Middle Aged ; Prospective Studies ; *Quality of Life ; *Quality-Adjusted Life Years ; Severity of Illness Index ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is associated with a substantial Quality of life impact on patients that has not been so far measured with a generic validated instrument.<br><br>METHODS: A prospective study was performed in 7 French acute-care settings in patients presenting with a bacteriologically-confirmed CDI. The EQ-5D-3&#x2009;L was filled in by patients at 7&#x2009;&#xb1;&#x2009;2&#x2009;days after CDI diagnosis to describe their state of health at that date as well as their state of health immediately before the CDI episode (baseline). Individual utility decrement was obtained by subtracting the corresponding utilities. The Quality Adjusted Life Year (QALY) loss was calculated by multiplying the days spent from baseline to the date of the interview, by the decrement of utility. A multivariate analysis of variance of the utility decrement according to CDI and patients characteristics was performed.<br><br>RESULTS: Eighty patients were enrolled (mean age: 69.4&#x2009;years, 55% females). The utility scores dropped from a mean 0.542 (SD: 0.391) at baseline to 0.050 (SD: 0.404) during the CDI episode with a mean adjusted utility decrement of 0.492 (SD: 0.398) point. This decrement increased significantly with CDI severity (Zar score&#x2009;&#x2265;&#x2009;3) (p&#x2009;=&#x2009;0.001), in patients with a positive baseline utility (p&#x2009;=&#x2009;0.032), in women as compared to men (p&#x2009;=&#x2009;0.041) and in patients aged more than 65&#x2009;years (p&#x2009;=&#x2009;0.041). No association with the Charlson index was found. The associated QALY loss not integrating the excess mortality was 0.028 (SD: 0.053).<br><br>CONCLUSIONS: The impact on quality of life of CDI episodes is major and translates in a substantial QALY loss despite their short duration.}, }
@article {pmid30633015, year = {2019}, author = {Gohil, AJ and Gupta, AK and Jesudason, MR and Nayak, S}, title = {Graciloplasty for Anal Incontinence-Is Electrical Stimulation Necessary?.}, journal = {Annals of plastic surgery}, volume = {82}, number = {6}, pages = {671-678}, doi = {10.1097/SAP.0000000000001770}, pmid = {30633015}, issn = {1536-3708}, mesh = {Adult ; Anal Canal/*surgery ; Cohort Studies ; Combined Modality Therapy ; Electric Stimulation/*methods ; Fecal Incontinence/diagnosis/*rehabilitation/*surgery ; Female ; Gracilis Muscle/*transplantation ; Humans ; Male ; Middle Aged ; Patient Positioning ; *Quality of Life ; Plastic Surgery Procedures/methods ; Recovery of Function/physiology ; Retrospective Studies ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {INTRODUCTION: Anal incontinence brings lot of social embarrassment, mental distress, dignity loss, anxiety, low confidence, and eventually a low self-esteem with a restricted social life to the affected person. Surgical repair is the mainstay of treatment for anal incontinence. However, some patients need additional procedures such as gluteoplasty, graciloplasty (adynamic and dynamic), artificial bowel sphincter, and sacral nerve stimulation, which help to reinforce or augment the anal sphincter.<br><br>METHODS: A retrospective analysis of 17 patients who underwent adynamic graciloplasty for reconstruction of anal sphincter from January 2008 to December 2017 was done. Demographic profile, fecal incontinence scores (Wexner score and KAMM score), and anal manometric findings were recorded pregraciloplasty and postgraciloplasty.<br><br>RESULTS: Of the total 17 patients, 9 were males and 8 were females. Satisfactory continence was achieved in 13 patients out of 17 (76.47%). Continence was defined as satisfactory for patients having a postoperative Wexner score of 2 or less and KAMM score of 4 or less. It was considered to be poor if the Wexner score was greater than 6 and KAMM score was greater than 8 in the follow-up period or if the stoma was not reversed.<br><br>CONCLUSIONS: Unstimulated or adynamic graciloplasty is a relatively safe procedure, has a short learning curve, is affordable, and avoids the additional implant-related complications. We feel that the unstimulated graciloplasty still has a significant role in the management of anal incontinence.}, }
@article {pmid30632438, year = {2019}, author = {Moutinho, BD and Baima, JP and Rigo, FF and Saad-Hossne, R and Rodrigues, J and Romeiro, FG and Sassaki, LY}, title = {Fecal microbiota transplantation in refractory ulcerative colitis - a case report.}, journal = {The Journal of international medical research}, volume = {47}, number = {2}, pages = {1072-1079}, pmid = {30632438}, issn = {1473-2300}, mesh = {Adolescent ; Colitis, Ulcerative/drug therapy/pathology/*therapy ; *Drug Resistance ; *Fecal Microbiota Transplantation ; Humans ; Immunosuppressive Agents/*pharmacology ; Male ; Prognosis ; *Salvage Therapy ; }, abstract = {Studies comparing gut microbiota profiles of inflammatory bowel disease (IBD) patients have shown several changes in microbiota composition, with marked reduction of local biodiversity relative to that of healthy controls. Modulation of the bacterial community is a promising strategy to reduce the proportion of harmful microorganisms and increase the proportion of beneficial bacteria; this is expected to prevent or treat IBD. The exact mechanism of fecal microbiota transplantation (FMT) remains unknown; however, replacing the host microbiota can reestablish gut microbial composition and function in IBD patients. The present report describes an ulcerative colitis patient who underwent FMT. A 17-year-old male with moderate to severe clinical activity, which was refractory to mesalazine, azathioprine, and infliximab, underwent FMT as alternative therapy. The patient exhibited clinical improvement after the procedure; however, the symptoms returned. A second FMT was performed 8 months after the first procedure, but the patient did not improve. In conclusion, despite the FMT failure observed in this patient, the procedure is a promising therapeutic option for IBD patients, and more in-depth studies of this method are needed.}, }
@article {pmid30632052, year = {2019}, author = {Allegretti, JR and Kao, D and Phelps, E and Roach, B and Smith, J and Ganapini, VC and Kassam, Z and Xu, H and Fischer, M}, title = {Risk of Clostridium difficile Infection with Systemic Antimicrobial Therapy Following Successful Fecal Microbiota Transplant: Should We Recommend Anti-Clostridium difficile Antibiotic Prophylaxis?.}, journal = {Digestive diseases and sciences}, volume = {64}, number = {6}, pages = {1668-1671}, pmid = {30632052}, issn = {1573-2568}, mesh = {Adult ; Aged ; Alberta ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; *Antibiotic Prophylaxis ; Boston ; Clostridium Infections/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Female ; *Gastrointestinal Microbiome ; Humans ; Indiana ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {INTRODUCTION: The risk of a new Clostridium difficile infection (CDI) after FMT is unknown if non-CDI antibiotics are required. It is uncertain if anti-CDI prophylaxis or probiotics would reduce risk. We therefore aimed to compare the risk of CDI with and without antibiotic exposure and the benefit of concomitant anti-CDI antibiotic or probiotic prophylaxis.<br><br>METHODS: This is a multicenter retrospective study carried out at three large FMT referral centers of patients who underwent FMT for recurrent CDI. Patients were assessed for antibiotic use, as well as concomitant use of prophylactic anti-CDI antibiotics or probiotics. Time to CDI recurrence after FMT was evaluated using the Kaplan-Meier method.<br><br>RESULTS: A total of 404 patients were included: 63% were females, with a mean age of 61.3&#x2009;&#xb1;&#x2009;18.8&#xa0;years. Mean length of post-FMT follow-up was 18.1&#x2009;&#xb1;&#x2009;11.9&#xa0;months (range 2.2-45.2). Among the entire cohort 8.1% (n&#x2009;=&#x2009;33) experienced a CDI recurrence. Overall, 111 patients (27.4%) used a non-CDI antibiotic, of which 16.2% (n&#x2009;=&#x2009;18) experienced a CDI recurrence. Patients who used non-CDI antibiotics were more likely to develop CDI (HR 8.44, 95% CI 4.21-16.93, p&#x2009;<&#x2009;0.001). The risk of CDI recurrence was not different between patients who received anti-CDI antibiotic prophylaxis to those who did not (HR&#x2009;=&#x2009;1.88, 95% CI 0.72-4.86, p&#x2009;=&#x2009;0.2); however, probiotic prophylaxis was associated with a greater risk of CDI recurrence (HR&#x2009;=&#x2009;2.65, 95% CI 1.02-6.86, p&#x2009;=&#x2009;0.045).<br><br>CONCLUSION: Non-CDI antibiotic use was not uncommon after successful FMT and significantly increased the risk of a new episode of CDI. In this study, we found that the prophylactic use of anti-CDI antibiotics or probiotics was not protective.}, }
@article {pmid30631977, year = {2019}, author = {Bocchini, R and Chiarioni, G and Corazziari, E and Pucciani, F and Torresan, F and Alduini, P and Bassotti, G and Battaglia, E and Ferrarini, F and Galeazzi, F and Londoni, C and Rossitti, P and Usai Satta, P and Iona, L and Marchi, S and Milazzo, G and Altomare, DF and Barbera, R and Bove, A and Calcara, C and D'Alba, L and De Bona, M and Goffredo, F and Manfredi, G and Naldini, G and Neri, MC and Turco, L and La Torre, F and D'Urso, AP and Berni, I and Balestri, MA and Busin, N and Boemo, C and Bellini, M}, title = {Pelvic floor rehabilitation for defecation disorders.}, journal = {Techniques in coloproctology}, volume = {23}, number = {2}, pages = {101-115}, pmid = {30631977}, issn = {1128-045X}, mesh = {Constipation/*rehabilitation ; Defecation ; Delphi Technique ; Fecal Incontinence/*rehabilitation ; Gastroenterology/*standards ; Humans ; Italy ; Pelvic Floor ; Practice Guidelines as Topic/*standards ; Societies, Medical/*standards ; }, abstract = {Pelvic floor rehabilitation is frequently recommended for defecation disorders, in both constipation and fecal incontinence. However, the lack of patient selection, together with the variety of rehabilitation methods and protocols, often jeopardize the results of this approach, causing difficulty in evaluating outcomes and addressing proper management, and above all, in obtaining scientific evidence for the efficacy of these methods for specific indications. The authors represent different gastroenterological and surgical scientific societies in Italy, and their aim was to identify the indications and agree on treatment protocols for pelvic floor rehabilitation of patients with defecation disorders. This was achieved by means of a modified Delphi method, utilizing a working team (10 members) which developed the statements and a consensus group (15 members, different from the previous ones) which voted twice also suggesting modifications of the statements.}, }
@article {pmid30630933, year = {2019}, author = {Jiang, X and Hall, AB and Arthur, TD and Plichta, DR and Covington, CT and Poyet, M and Crothers, J and Moses, PL and Tolonen, AC and Vlamakis, H and Alm, EJ and Xavier, RJ}, title = {Invertible promoters mediate bacterial phase variation, antibiotic resistance, and host adaptation in the gut.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6423}, pages = {181-187}, pmid = {30630933}, issn = {1095-9203}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 AT009708/AT/NCCIH NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/*genetics ; DNA, Bacterial/genetics ; DNA, Intergenic/*genetics ; Drug Resistance, Bacterial/*genetics ; *Gastrointestinal Microbiome ; Genome, Bacterial ; Humans ; *Promoter Regions, Genetic ; }, abstract = {Phase variation, the reversible alternation between genetic states, enables infection by pathogens and colonization by commensals. However, the diversity of phase variation remains underexplored. We developed the PhaseFinder algorithm to quantify DNA inversion-mediated phase variation. A systematic search of 54,875 bacterial genomes identified 4686 intergenic invertible DNA regions (invertons), revealing an enrichment in host-associated bacteria. Invertons containing promoters often regulate extracellular products, underscoring the importance of surface diversity for gut colonization. We found invertons containing promoters regulating antibiotic resistance genes that shift to the ON orientation after antibiotic treatment in human metagenomic data and in vitro, thereby mitigating the cost of antibiotic resistance. We observed that the orientations of some invertons diverge after fecal microbiota transplant, potentially as a result of individual-specific selective forces.}, }
@article {pmid30628108, year = {2019}, author = {Lai, CY and Sung, J and Cheng, F and Tang, W and Wong, SH and Chan, PKS and Kamm, MA and Sung, JJY and Kaplan, G and Chan, FKL and Ng, SC}, title = {Systematic review with meta-analysis: review of donor features, procedures and outcomes in 168 clinical studies of faecal microbiota transplantation.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {49}, number = {4}, pages = {354-363}, doi = {10.1111/apt.15116}, pmid = {30628108}, issn = {1365-2036}, mesh = {Adult ; Body Mass Index ; Clostridium Infections/*therapy ; Colitis, Ulcerative/therapy ; Crohn Disease/etiology ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Inflammatory Bowel Diseases/*therapy ; Male ; Mass Screening ; Tissue Donors/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is effective for Clostridium difficile infections (CDI) refractory to standard treatment and is being studied in other diseases.<br><br>AIM: To evaluate donor characteristics, procedures and clinical outcomes of FMT.<br><br>METHODS: We systematically reviewed FMT studies published up to 29 August 2018 using MEDLINE (R) and EMBASE and identified clinical studies with FMT donor information. We reported data on donor characteristics, screening criteria, administration, clinical outcomes and adverse events.<br><br>RESULTS: Among 5267 reports, 239 full-text articles were screened and 168 articles were included. FMT was performed commonly for CDI (n&#xa0;=&#xa0;108) and inflammatory bowel disease (IBD) (n&#xa0;=&#xa0;31). We reported characteristics of 1513 donors [58% male; mean age, 34.3&#xa0;years; mean body mass index, 21.6]. Donors in Asia were younger than the West (mean age 30.7 vs 32.9, P&#xa0;=&#xa0;0.00075). Less than 50% of studies screened donors for transmittable pathogens. Final cure rate for CDI was 95.6% (95% confidence interval [CI], 93.9%-97.1%) and final remission rates for ulcerative colitis (UC) and Crohn's disease (CD) were 39.6% (95% CI, 25.4%-54.6%) and 47.5% (95% CI, 29.4%-65.8%), respectively. Cure rates in CDI and final remission rates for CD and UC were comparable across all routes of FMT administration. Overall adverse event incidence was <1%, mostly GI-related. Adverse event rates did not differ significantly between routes of FMT administration or indication.<br><br>CONCLUSIONS: In a systematic review assessing donor characteristics and FMT efficacy, we observed heterogeneity in donor selection, application and outcomes of FMT. These data can facilitate standardisation of FMT protocols for various diseases.}, }
@article {pmid30627262, year = {2018}, author = {Tabbaa, OM and Aboelsoud, MM and Mattar, MC}, title = {Long-Term Safety and Efficacy of Fecal Microbiota Transplantation in the Treatment of Clostridium difficile Infection in Patients With and Without Inflammatory Bowel Disease: A Tertiary Care Center's Experience.}, journal = {Gastroenterology research}, volume = {11}, number = {6}, pages = {397-403}, pmid = {30627262}, issn = {1918-2805}, abstract = {BACKGROUND: Clostridium difficile infection (CDI) carries a large burden on the national public health with its high morbidity and mortality rates. Patients with inflammatory bowel disease (IBD) are generally at higher risk of infection, recurrence and complications. Therefore, the need for more reliable and safe therapy is necessary. Our study aims to evaluate long-term fecal microbiota transplant (FMT) outcomes in the general population compared to patients with IBD.<br><br>METHODS: A single center long-term follow-up study was conducted to evaluate the outcomes of FMT in patients with and without IBD. Prior to FMT data including demographics, prior treatment of CDI and severity of symptoms were gathered via chart review. Post FMT, all patients were surveyed after 2 days, 30 days and > 1 year to assess clinical and laboratory response. Our study outcomes included primary cure rate (negative CDI testing > 1 year after single FMT), and secondary cure rate (negative CDI testing > 1 year after repeat FMT or after an additional course of antibiotic with or without repeat FMT).<br><br>RESULTS: Seventy-eight patients with recurrent or refractory CDI and subsequent FMT treatment were included. Mean age was 57 years, and 69% were females and twenty-one (27%) had IBD. Primary cure rate was achieved in 77% of the cases while secondary cure rate reached 100% at the end of the study. IBD patients were younger with an average age of 47 years, and had more complains of abdominal pain (71%), and required escalation of therapy in 50% of patients.<br><br>CONCLUSIONS: FMT was effective in the eradication of CDI in patients with and without IBD, but with no significant symptoms improvement in patients with IBD. Future randomized control studies are needed to examine the long-term progression of IBD and quality of life in patients treated with FMT compared to standard therapy of antibiotics for recurrent CDI.}, }
@article {pmid30625497, year = {2019}, author = {de Clercq, NC and Frissen, MN and Davids, M and Groen, AK and Nieuwdorp, M}, title = {Weight Gain after Fecal Microbiota Transplantation in a Patient with Recurrent Underweight following Clinical Recovery from Anorexia Nervosa.}, journal = {Psychotherapy and psychosomatics}, volume = {88}, number = {1}, pages = {58-60}, doi = {10.1159/000495044}, pmid = {30625497}, issn = {1423-0348}, mesh = {Adult ; Anorexia Nervosa/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Thinness/microbiology/*therapy ; Weight Gain/*physiology ; }, }
@article {pmid30621961, year = {2019}, author = {Biardeau, X and Haddad, R and Chesnel, C and Charlanes, A and Hentzen, C and Turmel, N and Campagne, S and Capon, G and Fatton, B and Gamé, X and Jeandel, C and Kerdraon, J and Mares, P and Mezzadri, M and Petit, AC and Peyronnet, B and Soler, JM and Thuillier, C and Deffieux, X and Robain, G and Amarenco, G and Manceau, P and , }, title = {[Use of botulinum toxin A in pelvic floor dysfunctions in the elderly: A review].}, journal = {Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie}, volume = {29}, number = {4}, pages = {216-225}, doi = {10.1016/j.purol.2018.11.001}, pmid = {30621961}, issn = {1166-7087}, mesh = {Age Factors ; Aged ; Botulinum Toxins, Type A/*administration &amp; dosage/adverse effects ; Humans ; Injections ; Neuromuscular Agents/*administration &amp; dosage/adverse effects ; Pelvic Floor Disorders/*drug therapy/physiopathology ; Urinary Bladder Neck Obstruction/drug therapy ; Urinary Bladder, Neurogenic/drug therapy ; Urinary Bladder, Overactive/drug therapy ; }, abstract = {INTRODUCTION: The present article is the final report of a multi-disciplinary meeting supported by the GRAPPPA (group for research applied to pelvic floor dysfunctions in the elderly). The objective was to conduct a comprehensive review on the role of botulinum toxin A (BonTA) in the treatment of pelvic floor dysfunctions in the elderly.<br><br>METHODS: The present article, written as a comprehensive review of the literature, combines data issued from the scientific literature with expert's opinions. Review of the literature was performed using the online bibliographic database MedLine (National Library of Medicine). Regarding intra-detrusor BonTA injections, only articles focusing on elderly patients (>65 yo) were included. Regarding other localizations, given the limited number of data, all articles reporting outcomes of BonTA were included, regardless of studies population age. In case of missing or insufficient data, expert's opinions were formulated.<br><br>RESULTS: Although, available data are lacking in this specific population, it appears that BonTA could be used in the non-fraily elderly patients to treat overactive bladder or even neurogenic detrusor overactivity, with a success rate comparable to younger population at 3 months (88.9% vs. 91.2%), 6 months (49.4% vs. 52.1%) and 12 months (23.1% vs. 22.3%), as well as a significant decrease in number of voids per day (11.4 vs. 5.29 P<0.001) and in the number of pads per day (4.0 vs. 1.3, P<0.01). Furthermore, BonTA is likely to be offered in the future as a treatment of fecal incontinence and obstructed defecation syndrome symptoms. Concerning bladder outlet obstruction/voiding dysfunction symptoms, intra-urethral sphincter BonTA should not be recommended.<br><br>CONCLUSION: BonTA injections are of interest in the management of various pelvic floor dysfunctions in the elderly, and its various applications should be better evaluated in this specific population in order to further determine its safety and efficacy.}, }
@article {pmid30619136, year = {2018}, author = {Yang, H and Xiang, Y and Robinson, K and Wang, J and Zhang, G and Zhao, J and Xiao, Y}, title = {Gut Microbiota Is a Major Contributor to Adiposity in Pigs.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3045}, pmid = {30619136}, issn = {1664-302X}, abstract = {Different breeds of pigs vary greatly in their propensity for adiposity. Gut microbiota is known to play an important role in modulating host physiology including fat metabolism. However, the relative contribution of gut microbiota to lipogenic characteristics of pigs remains elusive. In this study, we transplanted fecal microbiota of adult Jinhua and Landrace pigs, two breeds of pigs with distinct lipogenic phenotypes, to antibiotic-treated mice. Our results indicated that, 4 weeks after fecal transplantation, the mice receiving Jinhua pigs' "obese" microbiota (JM) exhibited a different intestinal bacterial community structure from those receiving Landrace pigs' "lean" microbiota (LM). Notably, an elevated ratio of Firmicutes to Bacteroidetes and a significant diminishment of Akkermansia were observed in JM mice relative to LM mice. Importantly, mouse recipients resembled their respective porcine donors in many of the lipogenic characteristics. Similar to Jinhua pig donors, JM mice had elevated lipid and triglyceride levels and the lipoprotein lipase activity in the liver. Enhanced expression of multiple key lipogenic genes and reduced angiopoietin-like 4 (Angptl4) mRNA expression were also observed in JM mice, relative to those in LM mice. These results collectively suggested that gut microbiota of Jinhua pigs is more capable of enhancing lipogenesis than that of Landrace pigs. Transferability of the lipogenic phenotype across species further indicated that gut microbiota plays a major role in contributing to adiposity in pigs. Manipulation of intestinal microbiota will, therefore, have a profound impact on altering host metabolism and adipogenesis, with an important implication in the treatment of human overweight and obesity.}, }
@article {pmid30618824, year = {2018}, author = {Porras, D and Nistal, E and Martínez-Flórez, S and González-Gallego, J and García-Mediavilla, MV and Sánchez-Campos, S}, title = {Intestinal Microbiota Modulation in Obesity-Related Non-alcoholic Fatty Liver Disease.}, journal = {Frontiers in physiology}, volume = {9}, number = {}, pages = {1813}, pmid = {30618824}, issn = {1664-042X}, abstract = {Obesity and associated comorbidities, including non-alcoholic fatty liver disease (NAFLD), are a major concern to public well-being worldwide due to their high prevalence among the population, and its tendency on the rise point to as important threats in the future. Therapeutic approaches for obesity-associated disorders have been circumscribed to lifestyle modifications and pharmacological therapies have demonstrated limited efficacy. Over the last few years, different studies have shown a significant role of intestinal microbiota (IM) on obesity establishment and NAFLD development. Therefore, modulation of IM emerges as a promising therapeutic strategy for obesity-associated diseases. Administration of prebiotic and probiotic compounds, fecal microbiota transplantation (FMT) and exercise protocols have shown a modulatory action over the IM. In this review we provide an overview of current approaches targeting IM which have shown their capacity to counteract NAFLD and metabolic syndrome features in human patients and animal models.}, }
@article {pmid30616615, year = {2019}, author = {Sugita, K and Yanuma, N and Ohno, H and Takahashi, K and Kawano, K and Morita, H and Ohmori, K}, title = {Oral faecal microbiota transplantation for the treatment of Clostridium difficile-associated diarrhoea in a dog: a case report.}, journal = {BMC veterinary research}, volume = {15}, number = {1}, pages = {11}, pmid = {30616615}, issn = {1746-6148}, mesh = {Animals ; Clostridioides difficile ; Clostridium Infections/diagnosis/microbiology/therapy/*veterinary ; Diarrhea/microbiology/therapy/*veterinary ; Dog Diseases/diagnosis/microbiology/*therapy ; Dogs ; Fecal Microbiota Transplantation/*veterinary ; Male ; Real-Time Polymerase Chain Reaction/veterinary ; }, abstract = {BACKGROUND: Successful clinical outcomes of faecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection have been reported in humans and a marmoset. However, it has been unclear whether oral FMT was effective for the treatment of C. difficile-associated diarrhoea in dogs.<br><br>CASE PRESENTATION: An 8-month-old, intact male French bulldog was presented with a 4-month history of intermittent large bowel diarrhoea. Physical and clinical examinations did not identify any specific causes for diarrhoea. Real-time PCR analysis and immunochromatography detected C. difficile antigen and toxin A&amp;B genes and proteins in a faecal sample. Based on these findings, diarrhoea in the dog was considered to be induced by C. difficile-associated colitis. The dog was treated with oral FMT, in which a faecal solution obtained from a healthy beagle was orally administered to the subject. Stool consistency and frequency and faecal blood and mucus became normal 2-3&#x2009;days after oral FMT, and real-time PCR analysis and immunochromatography was negative for C. difficile antigen and toxin A&amp;B genes and proteins. No adverse events were observed.<br><br>CONCLUSION: The present case report demonstrated that oral FMT was an effective treatment for C. difficile-associated diarrhoea in a dog. The findings in this report provide a rationale to evaluate clinical efficacy of oral FMT for other gastrointestinal diseases in dogs.}, }
@article {pmid30616014, year = {2019}, author = {Huttner, BD and de Lastours, V and Wassenberg, M and Maharshak, N and Mauris, A and Galperine, T and Zanichelli, V and Kapel, N and Bellanger, A and Olearo, F and Duval, X and Armand-Lefevre, L and Carmeli, Y and Bonten, M and Fantin, B and Harbarth, S and , }, title = {A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {25}, number = {7}, pages = {830-838}, doi = {10.1016/j.cmi.2018.12.009}, pmid = {30616014}, issn = {1469-0691}, mesh = {Administration, Oral ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Carbapenem-Resistant Enterobacteriaceae/*drug effects ; Carrier State/drug therapy/microbiology ; Colistin/therapeutic use ; Drug Administration Schedule ; Drug Resistance, Multiple, Bacterial ; Enterobacteriaceae Infections/*drug therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Tertiary Care Centers ; beta-Lactamases ; }, abstract = {OBJECTIVES: Intestinal carriage with extended spectrum β-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE.<br><br>METHODS: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2&#xa0;&#xd7;&#xa0;10[6] IU 4&#xd7;/day; neomycin sulphate 500 mg 4&#xd7;/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35-48&#xa0;days after randomization (V4). ClinicalTrials.govNCT02472600. The trial was funded by the European Commission (FP7).<br><br>RESULTS: Thirty-nine patients (G&#xa0;=&#xa0;14; P&#xa0;=&#xa0;16; U&#xa0;=&#xa0;7; T&#xa0;=&#xa0;2) colonized by ESBL-E (n&#xa0;=&#xa0;36) and/or CPE (n&#xa0;=&#xa0;11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4-6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT).<br><br>CONCLUSIONS: Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted.}, }
@article {pmid30613670, year = {2018}, author = {Zhang, XY and Wang, YZ and Li, XL and Hu, H and Liu, HF and Li, D and Xiao, YM and Zhang, T}, title = {Safety of fecal microbiota transplantation in Chinese children: A single-center retrospective study.}, journal = {World journal of clinical cases}, volume = {6}, number = {16}, pages = {1121-1127}, pmid = {30613670}, issn = {2307-8960}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is the administration of fecal bacterial liquid from healthy donors to a recipient's digestive tract, which is recommended as a therapeutic method for recurrent Clostridium difficile infection (CDI). Many clinical trials focusing on different diseases are in progress. To date, scarce research and long-term follow-up have been conducted on FMT in children or on the proper guidelines. Our center first performed FMT to treat a 13-month-old boy with severe CDI in 2013. Until February 2018, our center had performed 114 pediatric FMT procedures in 49 subjects.<br><br>AIM: To investigate the safety of FMT in children.<br><br>METHODS: A retrospective study was conducted on 49 patients who underwent 114 FMT treatments at our hospital. All FMT processes followed uniform standards. Adverse events (AEs) related to FMT were divided into short-term (48 h post-FMT) and long-term (3 mo). All potential influencing factors for AEs, such as gender, age, time of FMT infusion, route of administration, disease type, immune function state, and donor relative genetic background, were analyzed as independent factors. The significant independent factors and risk ratio with 95% confidence interval (CI) were assessed by multivariate logistic regression analysis.<br><br>RESULTS: Forty-nine patients (mean age 68.1 mo, range 4 to 193 mo) were recruited. Their average follow-up time after the first FMT was 23.1 mo. The incidence of short-term AEs was 26.32% (30/114). The most common short-term AEs were abdominal pain, diarrhea, fever, and vomiting, which were all self-limited and symptom-free within 48 h. Two severe AEs occurred, and one patient died in the fourth week after FMT. All-cause mortality was 2.04%. As independent factors, age (P = 0.006) and immune state (P = 0.002) had significant effects. Age greater than 72 mo seemed to be correlated with more AEs than age 13 to 36 mo (P = 0.04). In multivariate logistic regression analysis, immune state was an independent risk factor for AE occurrence (P = 0.035), and the risk ratio in immunodeficient patients was 3.105 (95%CI: 1.080-8.923).<br><br>CONCLUSION: Although FMT was proven to be tolerated in children, we need to be more cautious with immunodeficient patients. The effect on children's long-term health is unpredictable.}, }
@article {pmid30613005, year = {2018}, author = {Guirong, YE and Minjie, Z and Lixin, YU and Junsheng, YE and Lin, Y and Lisha, S}, title = {[Gut microbiota in renal transplant recipients, patients with chronic kidney disease and healthy subjects].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {38}, number = {12}, pages = {1401-1408}, pmid = {30613005}, issn = {1673-4254}, mesh = {Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; *Healthy Volunteers ; Humans ; *Kidney ; Kidney Transplantation ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Renal Insufficiency, Chronic/*microbiology ; *Transplant Recipients ; }, abstract = {OBJECTIVE: Recent studies have shown that gut microbiota is associated with immunomodulation in transplant recipients, but the composition and function of gut microbiota in renal transplant recipients have not been understood.<br><br>METHODS: We analyzed the composition and function of gut microbiota in the fecal samples from 16 renal transplant (RT) recipients by deep sequencing of the 16S rRNA V3 variable region. The gut microbiota of RT recipients was compared to that of 84 patients with chronic kidney disease (CKD) and 53 healthy subjects.<br><br>RESULTS: The overall microbial structure of RT recipients was similar to that of CKD. The abundance of Firmicutes, Lachnospiraceae, Ruminococcaceae and Faecalibacterium was decreased and that of Bacteroidetes, Proteobacteria, Clostridiales, and Enterobacteriaceae was increased significantly in RT recipients and CKD patients compared with the healthy control subjects. Functional comparison revealed significantly enhanced carbohydrate metabolism and decreased metabolism of cofactors, vitamins, cell motility and genetic information processing in RT recipients and CKD patients. RT recipients and CKD patients also showed slight differences in that the abundance of Proteobacteria and Enterobacteriaceae and the pathways involving transport system members and carbohydrate metabolism were much greater in the former. We found that several beneficial genera in the Lachnospiraceae and Veillonellaceae were negatively correlated with such clinical markers as serum creatinine and blood urea nitrogen.<br><br>CONCLUSION: Our results suggested that alterations in the composition and function of gut microbiota are significantly correlated with the clinical conditions of in RT recipients, and future prospective studies of these correlations may provide evidence for predicting the clinical outcomes of RT recipients.}, }
@article {pmid30611533, year = {2019}, author = {Bermejo Boixareu, C and Ramos Martínez, A and Tutor-Ureta, P}, title = {Ninety-eight years old female successfully successfully treated with fecal microbiota transplantation after recurrent Clostridium difficile infection.}, journal = {Medicina clinica}, volume = {153}, number = {6}, pages = {e27}, doi = {10.1016/j.medcli.2018.11.024}, pmid = {30611533}, issn = {1578-8989}, mesh = {Aged, 80 and over ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Recurrence ; Remission Induction ; }, }
@article {pmid30610862, year = {2019}, author = {Hvas, CL and Dahl Jørgensen, SM and Jørgensen, SP and Storgaard, M and Lemming, L and Hansen, MM and Erikstrup, C and Dahlerup, JF}, title = {Fecal Microbiota Transplantation Is Superior to Fidaxomicin for Treatment of Recurrent Clostridium difficile Infection.}, journal = {Gastroenterology}, volume = {156}, number = {5}, pages = {1324-1332.e3}, doi = {10.1053/j.gastro.2018.12.019}, pmid = {30610862}, issn = {1528-0012}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Clostridioides difficile/*drug effects/pathogenicity ; Clostridium Infections/diagnosis/microbiology/*therapy ; Denmark ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Fidaxomicin/adverse effects/*therapeutic use ; Humans ; Male ; Middle Aged ; Recurrence ; Remission Induction ; Time Factors ; Treatment Outcome ; Vancomycin/adverse effects/*therapeutic use ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is recommended for treatment of recurrent Clostridium difficile infection (rCDI). We performed a single-center randomized trial to compare the effects of FMT with those of fidaxomicin and vancomycin.<br><br>METHODS: We studied consecutive adults with rCDI seen at a gastroenterology clinic in Denmark from April 5, 2016 through June 10, 2018. Patients were randomly assigned to a group that received FMT, applied by colonoscopy or nasojejunal tube, after 4-10 days of vancomycin (125 mg 4 times daily; FMTv; n&#xa0;= 24), 10 days of fidaxomicin (200 mg twice daily; n&#xa0;= 24), or 10 days of vancomycin (125 mg 4 times daily; n&#xa0;= 16). Patients who had rCDI after this course of treatment and patients who could not be randomly assigned to groups were offered rescue FMTv. The primary outcome was combined clinical resolution and a negative result from a polymerase chain reaction test for Clostridium difficile (CD) toxin 8 weeks after the allocated treatment. Secondary end points included clinical resolution at week&#xa0;8.<br><br>RESULTS: All 64 patients received their assigned treatment. The combination of clinical resolution and negative results from the test for CD were observed in 17 patients given FMTv (71%), 8 patients given fidaxomicin (33%), and 3 patients given vancomycin (19%; P&#xa0;= .009 for FMTv vs fidaxomicin; P&#xa0;= .001 for FMTv vs vancomycin; P&#xa0;= .31 for fidaxomicin vs vancomycin). Clinical resolution was observed in 22 patients given FMTv (92%), 10 patients given fidaxomicin (42%), and 3 patients given vancomycin (19%; P&#xa0;= .0002; P < .0001; P&#xa0;= .13). Results did not differ significantly between patients who received FMTv as their initial therapy and patients who received rescue FMTv. There was 1 serious adverse event that might have been related to FMTv.<br><br>CONCLUSIONS: In a randomized trial of patients with rCDI, we found the FMTv combination superior to fidaxomicin or vancomycin based on end points of clinical and microbiological resolution or clinical resolution alone. ClinicalTrials.gov, number NCT02743234; EudraCT, j.no 2015-003004-24.}, }
@article {pmid30606236, year = {2019}, author = {Dai, M and Zhang, T and Li, Q and Cui, B and Xiang, L and Ding, X and Rong, R and Bai, J and Zhu, J and Zhang, F}, title = {The bowel preparation for magnetic resonance enterography in patients with Crohn's disease: study protocol for a randomized controlled trial.}, journal = {Trials}, volume = {20}, number = {1}, pages = {1}, pmid = {30606236}, issn = {1745-6215}, mesh = {Adult ; Colonoscopy/*methods ; Crohn Disease/*diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Multicenter Studies as Topic ; Outcome Assessment, Health Care ; Randomized Controlled Trials as Topic ; Research Design ; }, abstract = {BACKGROUND: Adequate bowel preparation is required for magnetic resonance enterography (MRE), which can be achieved by administering contrast solution after mid-gut tubing or taking contrast solution orally. We present the design of randomized controlled trial (RCT) to compare the efficacy and compliance of bowel preparation between mid-gut tubing and oral administering for MRE in patients with Crohn's disease (CD).<br><br>METHODS/DESIGN: This is an open-label, multicenter RCT. Ninety-six patients with CD in need of MRE examination and mid-gut tubing (prepared for fecal microbiota transplantation and/or enteral nutrition), aged &#x2265;&#x2009;14&#x2009;years, will be included. Patients will be randomized 1:1 into either bowel preparation by oral administering (oral group) or bowel preparation through mid-gut transendoscopic enteral&#xa0;tubing&#xa0;(TET) (tubing group). The primary outcome measures are: (1) degree of discomfort before/during/after bowel preparation for MRE using a visual 5-grade scale (1&#x2009;=&#x2009;few, 5&#x2009;=&#x2009;very severe); and (2) grade of bowel distention evaluated by a 5-grade scale (1&#x2009;=&#x2009;0-20% segmental distention, 2&#x2009;=&#x2009;20-40% distention, 3&#x2009;=&#x2009;40-60% distention, 4&#x2009;=&#x2009;60-80% distention, 5&#x2009;=&#x2009;80-100% distention). The secondary outcome measure is the accuracy of lesion detection through MRE confirmed by colonoscopy which is evaluated by a 5-point scale.<br><br>DISCUSSION: The outcome of this study is expected to provide a novel effective clinical protocol of bowel preparation for MRE in patients with CD. We hope to highlight the concept of physician-patient satisfaction based on different methods of bowel preparation for MRE.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT03541733 . Registered on 30 May 2018.}, }
@article {pmid30604388, year = {2019}, author = {Osman, AEG and Luke, JJ}, title = {The Impact of the Fecal Microbiome on Cancer Immunotherapy.}, journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy}, volume = {33}, number = {1}, pages = {1-7}, doi = {10.1007/s40259-018-0328-8}, pmid = {30604388}, issn = {1179-190X}, support = {W81XWH-17-1-0265//U.S. Department of Defense/ ; }, mesh = {Gastrointestinal Microbiome/*immunology ; Graft vs Host Disease ; Humans ; Immunotherapy/methods ; Neoplasms/*microbiology/*therapy ; }, abstract = {Recent advances in culture-free methods of studying the human microbiome, coupled with strong bioinformatics tools, have provided new insights on the role of the human microbiome in health and disease. The human gut, in particular, houses a vast number and diverse variety of microbes. A plethora of evidence has demonstrated the significant effects of the gut microbiome on local and systemic immunity. Studies in hematopoietic stem cell transplantation recipients provided early evidence of the involvement of the gut microbiome in the development of graft-versus-host disease and its related mortality. Cancer immunotherapy and checkpoint inhibitors, in particular, harness the power of the host's immune system to fight a range of malignancies. Resistance to immunotherapy and fatal immune-related adverse events both continue to be challenges in the field. The role of the human gut microbiome in affecting the response to immunotherapy was recently uncovered through a series of preclinical and clinical studies. The evidence presented in these studies provides tremendous potential for gut microbes to be used for biomarker development and therapeutic intervention trials.}, }
@article {pmid30604248, year = {2019}, author = {Korsun, S and Liebig-Hoerl, G and Fuerst, A}, title = {Gracilis muscle transposition for treatment of recurrent anovaginal, rectovaginal, rectourethral, and pouch-vaginal fistulas in patients with inflammatory bowel disease.}, journal = {Techniques in coloproctology}, volume = {23}, number = {1}, pages = {43-52}, pmid = {30604248}, issn = {1128-045X}, mesh = {Adult ; Crohn Disease/*complications ; Female ; Fistula/etiology/*surgery ; Gracilis Muscle/*transplantation ; Humans ; Male ; Middle Aged ; Rectal Fistula/etiology/surgery ; Rectovaginal Fistula/etiology/surgery ; Recurrence ; Retrospective Studies ; Surgical Flaps ; Treatment Outcome ; Urethral Diseases/etiology/surgery ; Urinary Fistula/etiology/*surgery ; Vaginal Fistula/etiology/*surgery ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the effectiveness of gracilis muscle transposition (GMT) to treat recurrent anovaginal, rectovaginal, rectourethral, and pouch-vaginal fistulas in patients with inflammatory bowel disease (IBD).<br><br>METHODS: A retrospective study was conducted in patients with IBD who had GMT performed by a single surgeon between 2000 and 2018. Follow-up data regarding healing rate, complications, additional procedures, and stoma closure rate was collected.<br><br>RESULTS: A total of 30 women and 2 men had GMT.&#xa0;In all patients fistula&#xa0;was associated with Crohn's disease. In 1 female patient, contralateral gracilis transposition was required after a failed attempt at repair. The primary healing rate was 47% (15/32) and the definitive healing rate&#xa0;(healed by the time of data collection and after secondary procedures) was 71% (23/32). Additional surgical procedures due to fistula persistence or recurrence were performed on 17 patients (53%).At least 7 patients (21%) suffered complications including one wound infection with ischemia of the gracilis muscle. Stoma closure was successful in 18 of 31 cases of patients with stoma (58% of the patients).<br><br>CONCLUSIONS: GMT for the treatment of recurrent and complex anorectal fistulas in patients with IBD patient is eventually&#xa0;successful in almost 2/3 of patients.}, }
@article {pmid30604078, year = {2019}, author = {Fouladi, F and Brooks, AE and Fodor, AA and Carroll, IM and Bulik-Sullivan, EC and Tsilimigras, MCB and Sioda, M and Steffen, KJ}, title = {The Role of the Gut Microbiota in Sustained Weight Loss Following Roux-en-Y Gastric Bypass Surgery.}, journal = {Obesity surgery}, volume = {29}, number = {4}, pages = {1259-1267}, pmid = {30604078}, issn = {1708-0428}, support = {P30GM103332/NH/NIH HHS/United States ; }, mesh = {Adult ; Animals ; Feces/microbiology ; Female ; *Gastric Bypass/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Obesity, Morbid/*microbiology/*surgery ; Weight Gain/physiology ; Weight Loss/*physiology ; }, abstract = {BACKGROUND: The aim of the study was to investigate the role of the gut microbiota in weight regain or suboptimal weight loss following Roux-en-Y gastric bypass (RYGB).<br><br>MATERIALS AND METHODS: The gut microbiota composition in post-RYGB patients who experienced successful weight loss (SWL, n&#x2009;=&#x2009;6), post-RYGB patients who experienced poor weight loss (PWL, n&#x2009;=&#x2009;6), and non-surgical controls (NSC, n&#x2009;=&#x2009;6) who were age- and BMI-matched to the SWL group (NSC, n&#x2009;=&#x2009;6) were characterized through 16S rRNA gene sequencing. To further investigate the impact of the gut microbiota on weight profile, human fecal samples were transplanted into antibiotic-treated mice.<br><br>RESULTS: Orders of Micrococcales and Lactobacillales were enriched in SWL and PWL groups compared to the NSC group. No significant difference was observed in the gut microbiota composition between PWL and SWL patients. However, transfer of the gut microbiota from human patients into antibiotic-treated mice resulted in significantly greater weight gain in PWL recipient mice compared to SWL recipient mice. A few genera that were effectively transferred from humans to mice were associated with weight gain in mice. Among them, Barnesiella was significantly higher in PWL recipient mice compared to SWL and NSC recipient mice.<br><br>CONCLUSION: These results indicate that the gut microbiota are at least functionally, if not compositionally, different between PWL and SWL patients. Some taxa may contribute to weight gain after surgery. Future studies will need to determine the molecular mechanisms behind the effects of the gut bacteria on weight regain after RYGB.}, }
@article {pmid30602276, year = {2018}, author = {Stebel, R and Svačinka, R and Vojtilová, L and Freibergerová, M and Husa, P}, title = {Fecal bacteriotherapy in the treatment of Clostridium difficile infection.}, journal = {Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne}, volume = {67}, number = {3}, pages = {104-109}, pmid = {30602276}, issn = {1210-7913}, mesh = {Clostridioides difficile ; *Clostridium Infections/complications/therapy ; Czech Republic ; *Enterocolitis, Pseudomembranous/etiology/therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Prospective Studies ; Treatment Outcome ; }, abstract = {AIM: Using a prospective analysis to assess the success of faecal bacteriotherapy (FBT) in antibiotic-associated colitis due to Clostridium difficile. To analyse whether any of the factors according to which the treated patients can be categorized has a statistically significant effect on the therapeutic outcome.<br><br>MATERIALS AND METHODS: During the 2-year study period (2015-2016), 71 patients received FBT. After treatment, the patients were followed up by means of clinic visits or by phone. If colitis did not recur within eight weeks of follow-up, the treatment was considered successful.<br><br>RESULTS: The overall success rate was 76%, with statistically insignificant decline in recurrences. Subgroup analysis did not show any statistically significant difference in the success rate between the routes of administration, i.e. through a naso-enteral feeding tube and rectal enema. Likewise, there were no statistically significant differences in the success rate between the types of prior antibiotic therapy or between using fresh and cryo-stored stool suspension. No unexpected adverse event or lethality occurred during the study period.<br><br>CONCLUSIONS: Faecal bacteriotherapy is a successful and safe therapeutic alternative for recurrent C. difficile infections.}, }
@article {pmid30601771, year = {2019}, author = {Mankal, PK and Abed, J and Latte-Naor, S and Grinspan, A and Kotler, DP}, title = {Fidaxomicin and Fecal Microbiota Transplants for Severe Clostridium difficile Colitis.}, journal = {American journal of therapeutics}, volume = {26}, number = {1}, pages = {e115-e117}, doi = {10.1097/MJT.0000000000000573}, pmid = {30601771}, issn = {1536-3686}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Fidaxomicin/*therapeutic use ; Humans ; Male ; Middle Aged ; Treatment Outcome ; }, }
@article {pmid30598589, year = {2019}, author = {Ramai, D and Zakhia, K and Ofosu, A and Ofori, E and Reddy, M}, title = {Fecal microbiota transplantation: donor relation, fresh or frozen, delivery methods, cost-effectiveness.}, journal = {Annals of gastroenterology}, volume = {32}, number = {1}, pages = {30-38}, pmid = {30598589}, issn = {1108-7471}, support = {T32 DK007356/DK/NIDDK NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) has evolved into a robust and efficient means for treating recurrent Clostridium difficile infection (CDI). Our narrative review looks at the donor selection, preparation, delivery techniques and cost-effectiveness of FMT. We searched electronic databases, including PubMed, MEDLINE, Google Scholar, and Cochrane Databases, for studies that compared the biological effects of donor selection, fresh or frozen fecal preparation, and various delivery techniques. We also evaluated the cost-effectiveness and manually searched references to identify additional relevant studies. Overall, there is a paucity of studies that directly compare outcomes associated with related and non-related stool donors. However, inferences from prior studies indicate that the success of FMT does not depend on the donor-patient relationship. Over time, the use of unrelated donors has increased because of the formation of stool banks and the need to save processing time and capital. However, longitudinal studies are needed to clarify the optimal freezing time before microbial function declines. Several FMT techniques have been developed, such as colonoscopy, enema, nasogastric or nasojejunal tubes, and capsules. The comparable and high efficacy of FMT capsules, combined with their convenience, safety and aesthetically tolerable mode of delivery, makes it an attractive option for many patients. Cost-effective models comparing these various approaches support the use of FMT via colonoscopy as being the best strategy for the treatment of recurrent CDI.}, }
@article {pmid30598584, year = {2018}, author = {Greenberg, SA and Youngster, I and Cohen, NA and Livovsky, DM and Strahilevitz, J and Israeli, E and Melzer, E and Paz, K and Fliss-Isakov, N and Maharshak, N}, title = {Five years of fecal microbiota transplantation - an update of the Israeli experience.}, journal = {World journal of gastroenterology}, volume = {24}, number = {47}, pages = {5403-5414}, pmid = {30598584}, issn = {2219-2840}, mesh = {Aged ; Aged, 80 and over ; Capsules ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/microbiology/*therapy ; Diarrhea/diagnosis/microbiology/*therapy ; Fecal Microbiota Transplantation/instrumentation/*methods ; Female ; Humans ; Israel ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {AIM: To evaluate and describe the efficacy of fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in a national Israeli cohort.<br><br>METHODS: All patients who received FMT for recurrent (recurrence within 8 wk of the previous treatment) or refractory CDI from 2013 through 2017 in all the five medical centers in Israel currently performing FMT were included. Stool donors were screened according to the Israeli Ministry of Health guidelines. Clinical and laboratory data of patients were collected from patients' medical files, and they included indications for FMT, risk factors for CDI and disease severity. Primary outcome was FMT success (at least 2 mo free of CDI-related diarrhea post-FMT). Secondary outcomes included initial response to FMT (cessation of diarrhea within 7 d) and recurrence at 6 mo.<br><br>RESULTS: There were 111 FMTs for CDI, with a median age of 70 years [interquartile range (IQR): 53-82], and 42% (47) males. Fifty patients (45%) were treated via the lower gastrointestinal (LGI, represented only by colonoscopy) route, 37 (33%) via capsules, and 24 (22%) via the upper gastrointestinal (UGI) route. The overall success rate was 87.4% (97 patients), with no significant difference between routes of administration (P = 0.338). In the univariant analysis, FMT success correlated with milder disease (P = 0.01), ambulatory setting (P < 0.05) and lower Charlson comorbidity score (P < 0.05). In the multivariant analysis, only severe CDI [odd ratio (OR) = 0.14, P < 0.05] and inpatient FMT (OR = 0.19, P < 0.05) were each independently inversely related to FMT success. There were 35 (32%) patients younger than 60 years of age, and 14 (40%) of them had a background of inflammatory bowel disease.<br><br>CONCLUSION: FMT is a safe and effective treatment for CDI, with capsules emerging as a successful and well-tolerated route. Severe CDI is less likely to respond to FMT.}, }
@article {pmid30598508, year = {2019}, author = {Guo, Y and Crnkovic, CM and Won, KJ and Yang, X and Lee, JR and Orjala, J and Lee, H and Jeong, H}, title = {Commensal Gut Bacteria Convert the Immunosuppressant Tacrolimus to Less Potent Metabolites.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {47}, number = {3}, pages = {194-202}, pmid = {30598508}, issn = {1521-009X}, support = {K23 AI124464/AI/NIAID NIH HHS/United States ; }, mesh = {Administration, Oral ; Adult ; Aged ; Cells, Cultured ; Dose-Response Relationship, Drug ; Faecalibacterium prausnitzii/*metabolism ; Feces/chemistry ; Female ; Gastrointestinal Microbiome/*physiology ; Graft Rejection/immunology/prevention &amp; control ; Healthy Volunteers ; Humans ; Immunosuppression Therapy/methods ; Immunosuppressive Agents/administration &amp; dosage/analysis/*metabolism ; Kidney Transplantation/adverse effects ; Leukocytes, Mononuclear/drug effects ; Male ; Middle Aged ; Symbiosis ; Tacrolimus/administration &amp; dosage/analysis/*metabolism ; }, abstract = {Tacrolimus exhibits low and variable drug exposure after oral dosing, but the contributing factors remain unclear. Based on our recent report showing a positive correlation between fecal abundance of Faecalibacterium prausnitzii and oral tacrolimus dose in kidney transplant patients, we tested whether F. prausnitzii and other gut abundant bacteria are capable of metabolizing tacrolimus. Incubation of F. prausnitzii with tacrolimus led to production of two compounds (the major one named M1), which was not observed upon tacrolimus incubation with hepatic microsomes. Isolation, purification, and structure elucidation using mass spectrometry and nuclear magnetic resonance spectroscopy indicated that M1 is a C-9 keto-reduction product of tacrolimus. Pharmacological activity testing using human peripheral blood mononuclear cells demonstrated that M1 is 15-fold less potent than tacrolimus as an immunosuppressant. Screening of 22 gut bacteria species revealed that most Clostridiales bacteria are extensive tacrolimus metabolizers. Tacrolimus conversion to M1 was verified in fresh stool samples from two healthy adults. M1 was also detected in the stool samples from kidney transplant recipients who had been taking tacrolimus orally. Together, this study presents gut bacteria metabolism as a previously unrecognized elimination route of tacrolimus, potentially contributing to the low and variable tacrolimus exposure after oral dosing.}, }
@article {pmid30593419, year = {2019}, author = {Liptak, R and Gromova, B and Maronek, M and Gardlik, R}, title = {Reverse phenotype transfer via fecal microbial transplantation in inflammatory bowel disease.}, journal = {Medical hypotheses}, volume = {122}, number = {}, pages = {41-44}, doi = {10.1016/j.mehy.2018.10.017}, pmid = {30593419}, issn = {1532-2777}, mesh = {Animals ; Colitis/*therapy ; Colon/pathology ; Dextran Sulfate/chemistry ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*therapy ; Mice ; Permeability ; Phenotype ; }, abstract = {Inflammatory bowel disease (IBD) is characterized by a disbalance in the composition of intestinal microbiota. It is not clear whether such dysbiosis is a cause or a consequence of a disease state. Fecal microbiota transplantation (FMT) from a healthy donor to a patient or diseased animal is a valuable tool for targeted modification of microbiome leading to therapeutic response. Positive effect has been shown in therapy of a number of gastrointestinal as well as non-gastrointestinal diseases. In addition, FMT has been successfully used to transfer the diseased phenotype form a donor with the disease to a healthy recipient. However, targeted modification of the microbiome before the onset of colitis has not been shown previously. Based on our preliminary results, we propose the hypothesis of so called reverse phenotype transfer in IBD. This term describes the phenomenon, in which the transplantation of gut microbiota from a donor more sensitive to IBD to a healthy recipient leads to resistance of the recipient to IBD and vice versa. Mice that received FMT from donors with severe colitis have shown improved colitis score compared with mice that received FMT from donors more resistant to development of colitis. Such reverse phenotype transfer has broad implications, especially in terms of preventive medicine. However, detailed mechanisms need to be elucidated to conclude the validity of the phenomenon.}, }
@article {pmid30591021, year = {2018}, author = {Jenkins, SV and Vang, KB and Gies, A and Griffin, RJ and Jun, SR and Nookaew, I and Dings, RPM}, title = {Sample storage conditions induce post-collection biases in microbiome profiles.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {227}, pmid = {30591021}, issn = {1471-2180}, support = {P20 GM103625/GM/NIGMS NIH HHS/United States ; P20 GM125503/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/*isolation &amp; purification ; Feces/microbiology ; Mice ; *Microbiota ; Preservation, Biological/*methods ; Specimen Handling ; Temperature ; }, abstract = {BACKGROUND: Here we investigated the influence of different stabilization and storage strategies on the quality and composition of the fecal microbial community. Namely, same-day isolated murine DNA was compared to samples stored for 1 month in air at ambient temperature, with or without preservative buffers (i.e. EDTA and lysis buffer), different temperatures (i.e. 4 °C, - 20 °C, and - 80 °C), and hypoxic conditions.<br><br>RESULTS: Only storage in lysis buffer significantly reduced DNA content, yet without integrity loss. Storage in EDTA affected alpha diversity the most, which was also reflected in cluster separation. Distinct changes were also seen in the phyla and bacterial species abundance per storage strategy. Metabolic function analysis showed 22 pathways not significantly affected by storage conditions, whereas the tyrosine metabolism pathway was significantly changed in all strategies except by EDTA.<br><br>CONCLUSION: Each long-term storage strategy introduced a unique post-collection bias, which is important to take into account when interpreting data.}, }
@article {pmid30589368, year = {2019}, author = {Iwata, H and Goto, M and Sakai, N and Suemizu, H and Yamazaki, H}, title = {Predictability of human pharmacokinetics of diisononyl phthalate (DINP) using chimeric mice with humanized liver.}, journal = {Xenobiotica; the fate of foreign compounds in biological systems}, volume = {49}, number = {11}, pages = {1311-1322}, doi = {10.1080/00498254.2018.1564087}, pmid = {30589368}, issn = {1366-5928}, mesh = {Administration, Oral ; Adult ; Animals ; Carbon Radioisotopes ; Chimera ; Dose-Response Relationship, Drug ; Feces/chemistry ; Female ; Hepatocytes/transplantation ; Humans ; Liver/drug effects/*metabolism ; Male ; Mice, Inbred NOD ; Mice, SCID ; Oxidation-Reduction ; Phthalic Acids/administration &amp; dosage/metabolism/*pharmacokinetics ; }, abstract = {1. In order to investigate the pharmacokinetics of diisononyl phthalate (DINP) in humans, we administered [phenyl-U-[14]C]DINP at a dose of 50.0 mg/kg orally to chimeric mice (humanized-liver mice) in which the liver of TK-NOG mice (control mice) was replaced with human hepatocytes. 2. The plasma radioactivity concentrations peaked (18.0 and 59.9 µg equivalent of DINP/mL, respectively) at 2 h after administration in control and humanized-liver mice. Concentrations rose again at 8 h in controls, but not in humanized-liver mice. 3. The cumulative excretion rates in urine and feces, respectively, were 58.1% and 37.3% of the doses in controls up to 48 h, but were 86.0% and 7.7% in humanized-liver mice. 4. The main circulating metabolites in control and humanized-liver mice were monoisononyl phthalate (MINP) and the glucuronide of oxidized MINP, respectively. The urinary excretion ratio of the glucuronide of oxidized MINP in control mice was one-third of that in humanized-liver mice. 5. The present results suggested that the oxidation rates of the primary metabolite of DINP and their excretion routes to urine/feces were different for control and humanized-liver mice. Species differences in liver activities could be a determinant factor in the in vivo metabolism and disposition of diallyl phthalates such as DINP.}, }
@article {pmid30586712, year = {2019}, author = {Tang, TWH and Chen, HC and Chen, CY and Yen, CYT and Lin, CJ and Prajnamitra, RP and Chen, LL and Ruan, SC and Lin, JH and Lin, PJ and Lu, HH and Kuo, CW and Chang, CM and Hall, AD and Vivas, EI and Shui, JW and Chen, P and Hacker, TA and Rey, FE and Kamp, TJ and Hsieh, PCH}, title = {Loss of Gut Microbiota Alters Immune System Composition and Cripples Postinfarction Cardiac Repair.}, journal = {Circulation}, volume = {139}, number = {5}, pages = {647-659}, doi = {10.1161/CIRCULATIONAHA.118.035235}, pmid = {30586712}, issn = {1524-4539}, mesh = {Animals ; Anti-Bacterial Agents/*toxicity ; Bacteria/*drug effects/immunology/metabolism ; Disease Models, Animal ; Dysbiosis ; Fatty Acids/administration &amp; dosage/metabolism ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Lactobacillus/immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Monocytes/*immunology/metabolism/transplantation ; Myocardial Infarction/immunology/metabolism/*microbiology/pathology ; Myocardium/*immunology/metabolism/pathology ; Probiotics/administration &amp; dosage ; RAW 264.7 Cells ; }, abstract = {BACKGROUND: The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated.<br><br>METHODS: To investigate the effects of gut microbiota on cardiac repair after MI, C57BL/6J mice were treated with antibiotics 7 days before MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S rDNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by high-performance liquid chromatography. Fecal reconstitution, transplantation of monocytes, or dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI.<br><br>RESULTS: Antibiotic-treated mice displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells and SCFAs, more specifically acetate, butyrate, and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved after fecal reconstitution, transplantation of monocytes, or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community such as a reduction in Lactobacillus. Supplementing antibiotic-treated mice with a Lactobacillus probiotic before MI restored myeloid cell proportions, yielded cardioprotective effects, and shifted the balance of SCFAs toward propionate.<br><br>CONCLUSIONS: Gut microbiota-derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI and indeed human health and disease as a whole.}, }
@article {pmid30585500, year = {2019}, author = {Vigvári, S and Vincze, &#xc1; and Solt, J and Sipos, D and Feiszt, Z and Kovács, B and Kappéter, &#xc1; and Péterfi, Z}, title = {Experiences with fecal microbiota transplantation in Clostridium difficile infections via upper gastrointestinal tract.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {66}, number = {2}, pages = {179-188}, doi = {10.1556/030.65.2018.051}, pmid = {30585500}, issn = {1588-2640}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Intubation, Gastrointestinal ; Male ; *Microbiota ; Middle Aged ; Recurrence ; Treatment Outcome ; }, abstract = {Dramatic changes in the epidemiology of Clostridium difficile infections have been reported from the western world in the past decade. The proportion of severe cases is significantly elevating and clinicians now have to contend with the problem of additional and more frequent episodes of recurrences including an upward trend in the mortality rate. This situation led us to investigate the possibility of the fecal microbiota transplantation (FMT). An amount of 100 ml of fecal microbiota solution was instilled into a nasojejunal (NJ) tube in 16 cases and into a nasogastric (NG) tube in 44 cases. In all of the cases, where the solution was instilled via nasojejunal tubes, the symptoms resolved within 24 h. We did not note any recurrences in this group. When the material was flushed in through nasogastric tubes, the symptoms resolved in 39 (88.64%) cases within 24 h. In this group, we have experienced a recurrent episode of C. difficile infection in five (11.36%) cases. Three of them were cured with a second transplantation. We have found that in our practice the upper gastrointestinal tract methods had the primary cure rate of 91.67%, whereas the secondary cure rate is 96.67%. When we compared the NJ and NG methods, we have found that the differences in the outcomes are not significant statistically (p = 0.3113 using Fisher's exact probability test). In conclusion, FMT proved to be very effective, particularly in recurrent infections and in cases where conventional treatment had failed.}, }
@article {pmid30582442, year = {2019}, author = {Brandsma, E and Kloosterhuis, NJ and Koster, M and Dekker, DC and Gijbels, MJJ and van der Velden, S and Ríos-Morales, M and van Faassen, MJR and Loreti, MG and de Bruin, A and Fu, J and Kuipers, F and Bakker, BM and Westerterp, M and de Winther, MPJ and Hofker, MH and van de Sluis, B and Koonen, DPY}, title = {A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis.}, journal = {Circulation research}, volume = {124}, number = {1}, pages = {94-100}, pmid = {30582442}, issn = {1524-4571}, mesh = {Animals ; Aorta/*metabolism/pathology ; Aortic Diseases/genetics/metabolism/*microbiology/pathology ; Atherosclerosis/genetics/metabolism/*microbiology/pathology ; Bacteria/*metabolism ; Caspase 1/genetics/metabolism ; Cytokines/*metabolism ; Disease Models, Animal ; Disease Progression ; Dysbiosis ; Fatty Acids/metabolism ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Inflammation/genetics/metabolism/*microbiology/pathology ; Inflammation Mediators/*metabolism ; Mice, Knockout ; Plaque, Atherosclerotic ; Receptors, LDL/genetics/metabolism ; Time Factors ; }, abstract = {RATIONALE: Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis. A causal relation relationship between gut microbiota, inflammation, and atherosclerosis has not been explored previously.<br><br>OBJECTIVE: Here, we investigated whether a proinflammatory microbiota from Caspase1[-/-] (Casp1[-/-]) mice accelerates atherogenesis in Ldlr[-/-] mice.<br><br>METHOD AND RESULTS: We treated female Ldlr[-/-] mice with antibiotics and subsequently transplanted them with fecal microbiota from Casp1[-/-] mice based on a cohousing approach. Autologous transplantation of fecal microbiota of Ldlr[-/-] mice served as control. Mice were cohoused for 8 or 13 weeks and fed chow or high-fat cholesterol-rich diet. Fecal samples were collected, and factors related to inflammation, metabolism, intestinal health, and atherosclerotic phenotypes were measured. Unweighted Unifrac distances of 16S rDNA (ribosomal DNA) sequences confirmed the introduction of the Casp1[-/-] and Ldlr[-/-] microbiota into Ldlr[-/-] mice (referred to as Ldlr[-/-](Casp1[-/-]) or Ldlr[-/-](Ldlr[-/-]) mice). Analysis of atherosclerotic lesion size in the aortic root demonstrated a significant 29% increase in plaque size in 13-week high-fat cholesterol-fed Ldlr[-/-](Casp1[-/-]) mice compared with Ldlr[-/-](Ldlr[-/-]) mice. We found increased numbers of circulating monocytes and neutrophils and elevated proinflammatory cytokine levels in plasma in high-fat cholesterol-fed Ldlr[-/-](Casp1[-/-]) compared with Ldlr[-/-](Ldlr[-/-]) mice. Neutrophil accumulation in the aortic root of Ldlr[-/-](Casp1[-/-]) mice was enhanced compared with Ldlr[-/-](Ldlr[-/-]) mice. 16S-rDNA-encoding sequence analysis in feces identified a significant reduction in the short-chain fatty acid-producing taxonomies Akkermansia, Christensenellaceae, Clostridium, and Odoribacter in Ldlr[-/-](Casp1[-/-]) mice. Consistent with these findings, cumulative concentrations of the anti-inflammatory short-chain fatty acids propionate, acetate and butyrate in the cecum were significantly reduced in 13-week high-fat cholesterol-fed Ldlr[-/-](Casp1[-/-]) compared with Ldlr[-/-](Ldlr[-/-]) mice.<br><br>CONCLUSIONS: Introduction of the proinflammatory Casp1[-/-] microbiota into Ldlr[-/-] mice enhances systemic inflammation and accelerates atherogenesis.}, }
@article {pmid30580506, year = {2018}, author = {Xu, Z and Liu, Z and Dong, X and Hu, T and Wang, L and Li, J and Liu, X and Sun, J}, title = {Fecal Microbiota Transplantation from Healthy Donors Reduced Alcohol-induced Anxiety and Depression in an Animal Model of Chronic Alcohol Exposure.}, journal = {The Chinese journal of physiology}, volume = {61}, number = {6}, pages = {360-371}, doi = {10.4077/CJP.2018.BAH633}, pmid = {30580506}, issn = {0304-4920}, support = {NO. 81671320//Natural Science Foundation of China/International ; NO. 2016GSF201054//Key Research Plan of Shandong Province/International ; }, mesh = {Animals ; Anxiety ; *Depression ; Ethanol ; *Fecal Microbiota Transplantation ; Feces ; Mice ; }, abstract = {Alcohol addiction can cause brain dysfunction and threatens both individuals and society. Recently, emerging studies have suggested the dysbiosis of gut microbiota induced by alcohol exposure contributed to the reward-seeking behaviors as well as anxiety, depression. In the current study, animal model of chronic alcohol exposure was established by providing mice with gradient concentrations of alcohol from 2%, 4%, and 6% to 8% for 21 days. Moreover, three fecal microbiota transplantation (FMT) plans were innovatively designed to explore the potential effects of FMT from 3 healthy donors on alcohol-induced neuropsychic behaviors. To our knowledge, for the first time, we found that anxiety and depression after alcohol intake were gradually relieved with the extension of transplantation. Although the two-week FMT starting at the end of alcohol treatment had few effects, the transplantation started at 8% ethanol exposure alleviated alcohol-induced depression in tail suspension test. More importantly, accompanied by three-week exposure, the five-week FMT significantly decreased anxiety-like behaviors in open field test and depression in tail suspension test. These data validated the role of gut microbiota in alcohol addiction and indicated the modulation of healthy donor FMT on alcohol-related anxiety and depression, providing a new target for treating alcohol addiction by targeting microbiota.}, }
@article {pmid30578461, year = {2019}, author = {Nobili, V and Mosca, A and Alterio, T and Cardile, S and Putignani, L}, title = {Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT).}, journal = {Advances in experimental medicine and biology}, volume = {1125}, number = {}, pages = {85-100}, doi = {10.1007/5584_2018_318}, pmid = {30578461}, issn = {0065-2598}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Non-alcoholic Fatty Liver Disease/*therapy ; Probiotics/*therapeutic use ; Randomized Controlled Trials as Topic ; }, abstract = {Pediatric obesity is rising worldwide leading the worrying phenomenon of nonalcoholic fatty liver disease (NAFLD) to shift into one of the most frequent causes of chronic liver illness in childhood. Occurrence of NAFLD depends on several factors such as the geographical area and the diagnostic modalities used; overall it ranges between 3% and 10% of pediatric population, increasing up to 70% in patients with metabolic comorbidities (Manco M, Bottazzo G, DeVito R et al, J Am Coll Nutr 27:667-676, 2008).Recent findings have related the intestinal microbiota to a plethora of pathological conditions, including type 2 diabetes (T2D), obesity, and nonalcoholic steatohepatitis (NASH). One of the emerging areas of the study is the link between liver diseases and gut microbiome, which has added new information to the understanding of the so-called gut-liver axis.In order to address the role of gut microbiome in NAFLD onset and progression, it is necessary to "decipher" operational codes for microbiome investigation within the context of advanced laboratory medicine to capture microbiome features and, hence, to address the function of the intestinal microbiome within the gut microbiota-liver axis.Results of these investigations have allowed the beginning of implementing the usage of probiotics and symbiotics in the medical approach of obesity and NAFLD in adults and children. Several randomized clinical trials (RCTs) have been already published on fecal microbiota transplantation (FMT), T2D, NASH, and inflammatory bowel disease (IBD).This review proposes to describe the current state of knowledge on the ways fatty liver diseases can be addressed with nutritional interventions, probiotics, symbiotics, and FMT.}, }
@article {pmid30576642, year = {2019}, author = {Singh, S and Feuerstein, JD and Binion, DG and Tremaine, WJ}, title = {AGA Technical Review on the Management of Mild-to-Moderate Ulcerative Colitis.}, journal = {Gastroenterology}, volume = {156}, number = {3}, pages = {769-808.e29}, pmid = {30576642}, issn = {1528-0012}, support = {K23 DK117058/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Colitis, Ulcerative/*diagnosis/*drug therapy ; Disease Management ; Disease Progression ; Female ; Gastroenterology/*standards ; Humans ; Male ; Mesalamine/therapeutic use ; Prognosis ; Risk Assessment ; Severity of Illness Index ; Societies, Medical ; Sulfasalazine/therapeutic use ; Treatment Outcome ; United States ; }, abstract = {Most patients with ulcerative colitis (UC) have mild-to-moderate disease activity, with low risk of colectomy, and are managed by primary care physicians or gastroenterologists. Optimal management of these patients decreases the risk of relapse and proximal disease extension, and may prevent disease progression, complications, and need for immunosuppressive therapy. With several medications (eg, sulfasalazine, diazo-bonded 5-aminosalicylates [ASA], mesalamines, and corticosteroids, including budesonide) and complex dosing formulations, regimens, and routes, to treat a disease with variable anatomic extent, there is considerable practice variability in the management of patients with mild-moderate UC. Hence, the American Gastroenterological Association prioritized clinical guidelines on this topic. To inform clinical guidelines, this technical review was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation framework for interventional studies. Focused questions included the following: (1) comparative effectiveness and tolerability of different oral 5-ASA therapies (sulfalsalazine vs diazo-bonded 5-ASAs vs mesalamine; low- (<2 g) vs standard (2-3 g/d) vs high-dose (>3 g/d) mesalamine); (2) comparison of different dosing regimens (once-daily vs multiple times per day dosing) and routes (oral vs rectal vs both oral and rectal); (3) role of oral budesonide in patients mild-moderate UC; (4) comparative effectiveness and tolerability of rectal 5-ASA and corticosteroid formulations in patients with distal colitis; and (5) role of alternative therapies like probiotics, curcumin, and fecal microbiota transplantation in the management of mild-moderate UC.}, }
@article {pmid30575732, year = {2018}, author = {Coryell, M and McAlpine, M and Pinkham, NV and McDermott, TR and Walk, ST}, title = {The gut microbiome is required for full protection against acute arsenic toxicity in mouse models.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {5424}, pmid = {30575732}, issn = {2041-1723}, support = {F31 ES026884/ES/NIEHS NIH HHS/United States ; R01 CA215784/CA/NCI NIH HHS/United States ; R21 ES026411/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Animals ; Arsenic/metabolism ; Arsenic Poisoning/*prevention &amp; control ; Faecalibacterium prausnitzii/*physiology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; *Germ-Free Life ; Humans ; Inactivation, Metabolic ; Male ; Methyltransferases/physiology ; Mice, Inbred C57BL ; Mice, Transgenic ; Young Adult ; }, abstract = {Arsenic poisons an estimated 200 million people worldwide through contaminated food and drinking water. Confusingly, the gut microbiome has been suggested to both mitigate and exacerbate arsenic toxicity. Here, we show that the microbiome protects mice from arsenic-induced mortality. Both antibiotic-treated and germ-free mice excrete less arsenic in stool and accumulate more arsenic in organs compared to control mice. Mice lacking the primary arsenic detoxification enzyme (As3mt) are hypersensitive to arsenic after antibiotic treatment or when derived germ-free, compared to wild-type and/or conventional counterparts. Human microbiome (stool) transplants protect germ-free As3mt-KO mice from arsenic-induced mortality, but protection depends on microbiome stability and the presence of specific bacteria, including Faecalibacterium. Our results demonstrate that both a functional As3mt and specific microbiome members are required for protection against acute arsenic toxicity in mouse models. We anticipate that the gut microbiome will become an important explanatory factor of disease (arsenicosis) penetrance in humans, and a novel target for prevention and treatment strategies.}, }
@article {pmid30570191, year = {2019}, author = {Ban, H and Miura, K and Ishizuka, K and Kaneko, N and Taniguchi, Y and Nagasawa, T and Shirai, Y and Yabuuchi, T and Takagi, Y and Goto, A and Hattori, M}, title = {Clinical characteristics of Campylobacter enteritis after pediatric renal transplantation: A retrospective analysis from single center.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {21}, number = {2}, pages = {e13040}, doi = {10.1111/tid.13040}, pmid = {30570191}, issn = {1399-3062}, mesh = {Adolescent ; Anti-Bacterial Agents/therapeutic use ; Bacteremia/*diagnosis ; Campylobacter Infections/complications/*diagnosis/drug therapy ; Campylobacter jejuni ; Child ; Enteritis/*diagnosis/drug therapy/microbiology ; Feces/microbiology ; Female ; Humans ; Immunocompromised Host ; Kidney Transplantation/*adverse effects ; Male ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: There are few reports of patients with Campylobacter enteritis after renal transplantation, and only a few case reports of bacteremia have been published. Although antibiotic therapy for 3-5 days has been recommended for immunocompromised patients, the optimal treatment for Campylobacter enteritis after renal transplantation has not been established. This study aimed to clarify the clinical characteristics and treatment outcomes of Campylobacter enteritis after pediatric renal transplantation.<br><br>METHODS: This retrospective study included patients who underwent pediatric renal transplantation and were found to have Campylobacter species in stool cultures between January 2014 and May 2017.<br><br>RESULTS: This study included eight patients who underwent pediatric renal transplantation. The median age at the time of renal transplantation was 14&#xa0;years, and the median period between transplantation and disease occurrence was 4.6&#xa0;years. Clinical symptoms were abdominal pain for eight patients, diarrhea for eight patients, fever for seven patients, vomiting for three patients, and headache for three patients. Campylobacter jejuni was isolated from the stool cultures of all patients. The median administration period of antibiotics as initial therapy was 7&#xa0;days (range, 4-11&#xa0;days). However, clinical relapse was observed in four patients after completing antibiotic therapy. Patients who experienced clinical relapse required a second course of antibiotic therapy for a median duration of 7&#xa0;days (range, 5-10&#xa0;days).<br><br>CONCLUSIONS: Patients with Campylobacter enteritis after pediatric renal transplantation are at high risk for clinical relapse and may require a longer duration of antibiotic therapy than that generally described.}, }
@article {pmid30563687, year = {2019}, author = {Marion, O and Lhomme, S and Del Bello, A and Abravanel, F and Esposito, L and Hébral, AL and Lavayssière, L and Cointault, O and Ribes, D and Izopet, J and Kamar, N}, title = {Monitoring hepatitis E virus fecal shedding to optimize ribavirin treatment duration in chronically infected transplant patients.}, journal = {Journal of hepatology}, volume = {70}, number = {1}, pages = {206-209}, doi = {10.1016/j.jhep.2018.09.011}, pmid = {30563687}, issn = {1600-0641}, mesh = {Aged ; Antiviral Agents/therapeutic use ; Chronic Disease ; Duration of Therapy ; Feces/virology ; Female ; Genotype ; Hepatitis E/*drug therapy/virology ; Hepatitis E virus/*drug effects/genetics ; Humans ; Male ; Middle Aged ; *Organ Transplantation ; RNA, Viral/*analysis ; Ribavirin/*therapeutic use ; }, }
@article {pmid30563199, year = {2018}, author = {Lin, C and Wan, J and Su, Y and Zhu, W}, title = {Effects of Early Intervention with Maternal Fecal Microbiota and Antibiotics on the Gut Microbiota and Metabolite Profiles of Piglets.}, journal = {Metabolites}, volume = {8}, number = {4}, pages = {}, pmid = {30563199}, issn = {2218-1989}, support = {31572414 and 31872362//the National Natural Science Foundation of China/ ; KYCYL201502-2//the Fundamental Research Funds for the Central Universities/ ; }, abstract = {We investigated the effects of early intervention with maternal fecal microbiota and antibiotics on gut microbiota and the metabolites. Five litters of healthy neonatal piglets (Duroc × Landrace × Yorkshire, nine piglets in each litter) were used. Piglets in each litter were orally treated with saline (CO), amoxicillin treatment (AM), or maternal fecal microbiota transplantation (MFMT) on days 1[-]6, with three piglets in each treatment. Results were compared to the CO group. MFMT decreased the relative abundances of Clostridium sensu stricto and Parabacteroides in the colon on day 7, whereas the abundance of Blautia increased, and the abundance of Corynebacterium in the stomach reduced on day 21. AM reduced the abundance of Arcanobacterium in the stomach on day 7 and reduced the abundances of Streptococcus and Lachnoclostridium in the ileum and colon on day 21, respectively. The metabolite profile indicated that MFMT markedly influenced carbohydrate metabolism and amino acid (AA) metabolism on day 7. On day 21, carbohydrate metabolism and AA metabolism were affected by AM. The results suggest that MFMT and AM discriminatively modulate gastrointestinal microflora and alter the colonic metabolic profiles of piglets and show different effects in the long-term. MFMT showed a location-specific influence on the gastrointestinal microbiota.}, }
@article {pmid30563034, year = {2018}, author = {Moelling, K and Broecker, F and Willy, C}, title = {A Wake-Up Call: We Need Phage Therapy Now.}, journal = {Viruses}, volume = {10}, number = {12}, pages = {}, pmid = {30563034}, issn = {1999-4915}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Bacterial Infections/*therapy ; Bacteriophages/physiology ; Clinical Trials as Topic ; Fecal Microbiota Transplantation ; History, 20th Century ; History, 21st Century ; Humans ; Mice ; Phage Therapy/adverse effects/history/*methods ; }, abstract = {The rise of multidrug-resistant bacteria has resulted in an increased interest in phage therapy, which historically preceded antibiotic treatment against bacterial infections. To date, there have been no reports of serious adverse events caused by phages. They have been successfully used to cure human diseases in Eastern Europe for many decades. More recently, clinical trials and case reports for a variety of indications have shown promising results. However, major hurdles to the introduction of phage therapy in the Western world are the regulatory and legal frameworks. Present regulations may take a decade or longer to be fulfilled. It is of urgent need to speed up the availability of phage therapy.}, }
@article {pmid30561131, year = {2019}, author = {Limketkai, BN and Hendler, S and Ting, PS and Parian, AM}, title = {Fecal Microbiota Transplantation for the Critically Ill Patient.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {34}, number = {1}, pages = {73-79}, doi = {10.1002/ncp.10228}, pmid = {30561131}, issn = {1941-2452}, mesh = {Critical Illness/*therapy ; Diarrhea/therapy ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; }, abstract = {The gut microbiome has been implicated in a diversity of diseases, such as irritable bowel syndrome, inflammatory bowel disease, hepatic steatosis, metabolic syndrome, obesity, and anxiety. Current research also suggests the presence of a bidirectional relationship between the composition of the gut microbiome and critical illness. In the critical care setting, multiple factors (eg, use of antibiotics, aberrant nutrition, bloodstream infections, bowel ischemia, and abnormal bowel motility) strongly contribute to intestinal dysbiosis. Conversely, early studies have associated intestinal dysbiosis with worse clinical outcomes in the intensive care unit (ICU), such as infection, organ failure, and mortality. The possibility of intestinal dysbiosis influencing these clinical outcomes has prompted the question of whether microbiome manipulation strategies, such as fecal microbiota transplantation (FMT), may have a role in the management of critical illness. After a literature search of FMT used in the ICU for indications other than Clostridium difficile infections, we found 4 case reports that describe the use of FMT in 5 critically ill patients with systemic inflammatory responses and no clear source of infection. This review discusses the relationship between the gut microbiome and critical illness, early data on the use of FMT in critical care, and safety considerations of FMT in the critically ill and immunocompromised populations.}, }
@article {pmid30558014, year = {2018}, author = {Cai, TT and Ye, XL and Yong, HJ and Song, B and Zheng, XL and Cui, BT and Zhang, FM and Lu, YB and Miao, H and Ding, DF}, title = {Fecal microbiota transplantation relieve painful diabetic neuropathy: A case report.}, journal = {Medicine}, volume = {97}, number = {50}, pages = {e13543}, pmid = {30558014}, issn = {1536-5964}, mesh = {Diabetic Neuropathies/microbiology/*surgery ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Middle Aged ; Remission Induction/methods ; }, abstract = {RATIONALE: Fecal microbiota transplantation (FMT) has been used in a wide variety of diseases. In this article, we reported a 46-year-old female with diabetic neuropathy (DN) achieved remission by the treatment of FMT.<br><br>PATIENT CONCERNS: The patient with an 8-year history of diabetes and hypertension was admitted to hospital due to sensitive pain of her right thigh and poor blood glucose control. The traditional hypoglycemic and analgesic treatment were useless to her symptoms.<br><br>DIAGNOSIS: Diabetic-induced neuropathy was considered.<br><br>INTERVENTIONS: This patient received twice FMTs for 3 months.<br><br>OUTCOMES: After twice FMTs, the clinical response of patient was pleasant. The glycemic control was improved, with a remarkable relief of the symptoms of painful DN in particular. No obvious adverse effects were observed during the FMTs and follow-up observation-testing.<br><br>LESSONS: We proposed that FMT could be a promising treatment in patients with diabetes or diabetes-related complications like DN. FMT also appeared to be definitely safer and more tolerable than the pharmacologic treatment in patients with DN.}, }
@article {pmid30554391, year = {2019}, author = {Bianchi, F and Duque, ALRF and Saad, SMI and Sivieri, K}, title = {Gut microbiome approaches to treat obesity in humans.}, journal = {Applied microbiology and biotechnology}, volume = {103}, number = {3}, pages = {1081-1094}, doi = {10.1007/s00253-018-9570-8}, pmid = {30554391}, issn = {1432-0614}, support = {(2013/50506-8; 2015/13965-0; 2015/08228-6)//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; }, mesh = {Exercise ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Obesity/*therapy ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {The rising worldwide prevalence of obesity has become a major concern having many implications for the public health and the economy. It is well known that many factors such as lifestyle, increased intake of foods high in fat and sugar and a host's genetic profile can lead to obesity. Besides these factors, recent studies have pointed to the gut microbiota composition as being responsible for the development of obesity. Since then, many efforts have been made to understand the link between the gut microbiota composition and obesity, as well as the role of food ingredients, such as pro- and prebiotics, in the modulation of the gut microbiota. Studies involving the gut microbiota composition of obese individuals are however still controversial, making it difficult to treat obesity. In this sense, this mini-review deals with obesity and the relationship with gut microbiota, summarising the principal findings on gut microbiome approaches for treating obesity in humans.}, }
@article {pmid30551119, year = {2019}, author = {McClave, SA and Martindale, RG}, title = {Why do current strategies for optimal nutritional therapy neglect the microbiome?.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {60}, number = {}, pages = {100-105}, doi = {10.1016/j.nut.2018.09.024}, pmid = {30551119}, issn = {1873-1244}, mesh = {Critical Illness/*therapy ; Dysbiosis/*immunology/*therapy ; Enteral Nutrition/methods ; Gastrointestinal Microbiome/*immunology ; Humans ; Nutritional Support/*methods ; }, abstract = {Strategies for providing optimal nutritional therapy have evolved over time, with the emphasis on specific directives (such as route, use of immunonutrition, high protein, organ-specific formulas, etc.), achieving variable degrees of success for improving outcomes in the intensive care unit. As the largest immune organ in the body comprising the largest interface between the host and the external environment, the gut can have an amplifying effect on a pattern of dysbiosis, immune dysregulation, and multiple organ failure seen in the critically ill patient. Conversely, maintenance of gut integrity can serve to restore a pattern of homeostasis, appropriate immune responses, symbiosis, and clinical recovery. Simply providing refined polymeric formulas as enteral nutrition may not take full advantage of the potential for optimal outcome that could be derived by giving therapy designed to directly stimulate gut defenses and support the intestinal microbiota. This article describes a series of strategies (such as use of intact whole food formulas, soluble fiber, fecal microbial transplantation, serum bovine immunoglobulin, or agents to promote commensal behavior) that should modulate the gut microbiome and shift the critically ill patient toward a pattern of health and recovery.}, }
@article {pmid30546094, year = {2019}, author = {Libertucci, J and Young, VB}, title = {The role of the microbiota in infectious diseases.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {35-45}, doi = {10.1038/s41564-018-0278-4}, pmid = {30546094}, issn = {2058-5276}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; }, mesh = {Communicable Disease Control/*methods ; Communicable Diseases/microbiology/transmission ; Disease Susceptibility/*microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Tract/microbiology ; Humans ; Metagenome/genetics ; Microbiota/*genetics ; Prebiotics/*microbiology ; Probiotics/*therapeutic use ; Respiratory Mucosa/microbiology ; }, abstract = {The human body is colonized by a diverse community of microorganisms collectively referred to as the microbiota. Here, we describe how the human microbiota influences susceptibility to infectious diseases using examples from the respiratory, gastrointestinal and female reproductive tract. We will discuss how interactions between the host, the indigenous microbiota and non-native microorganisms, including bacteria, viruses and fungi, can alter the outcome of infections. This Review Article will highlight the complex mechanisms by which the microbiota mediates colonization resistance, both directly and indirectly, against infectious agents. Strategies for the therapeutic modulation of the microbiota to prevent or treat infectious diseases will be discussed, and we will review potential therapies that directly target the microbiota, including prebiotics, probiotics, synbiotics and faecal microbiota transplantation.}, }
@article {pmid30545582, year = {2019}, author = {Benavent Boladeras, R and Ariño Blasco, S}, title = {[Faecal transplantation in geriatrics].}, journal = {Revista espanola de geriatria y gerontologia}, volume = {54}, number = {2}, pages = {119-120}, doi = {10.1016/j.regg.2018.10.005}, pmid = {30545582}, issn = {1578-1747}, mesh = {Aged, 80 and over ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Male ; }, }
@article {pmid30543777, year = {2018}, author = {Hu, J and Ma, L and Nie, Y and Chen, J and Zheng, W and Wang, X and Xie, C and Zheng, Z and Wang, Z and Yang, T and Shi, M and Chen, L and Hou, Q and Niu, Y and Xu, X and Zhu, Y and Zhang, Y and Wei, H and Yan, X}, title = {A Microbiota-Derived Bacteriocin Targets the Host to Confer Diarrhea Resistance in Early-Weaned Piglets.}, journal = {Cell host &amp; microbe}, volume = {24}, number = {6}, pages = {817-832.e8}, doi = {10.1016/j.chom.2018.11.006}, pmid = {30543777}, issn = {1934-6069}, mesh = {Animals ; Bacteriocins/*metabolism ; Cell Line ; Cell Membrane/metabolism ; Diarrhea/microbiology/*prevention &amp; control/*veterinary ; Enterocytes/metabolism ; Feces/microbiology ; *Gastrointestinal Microbiome ; Keratin-19/genetics/metabolism ; Lactobacillus gasseri/*metabolism ; Mice ; Specific Pathogen-Free Organisms ; Swine/*microbiology ; Weaning ; }, abstract = {Alternatives to antibiotics for preventing diarrhea in early-weaned farm animals are sorely needed. CM piglets (a native Chinese breed) are more resistant to early-weaning stress-induced diarrhea than the commercial crossbred LY piglets. Transferring fecal microbiota, but not saline, from healthy CM into LY piglets by oral administration prior to early weaning conferred diarrhea resistance. By comparing the relative abundance of intestinal microbiota in saline and microbiota transferred LY piglets, we identified and validated Lactobacillus gasseri LA39 and Lactobacillus frumenti as two bacterial species that mediate diarrhea resistance. Diarrhea resistance depended on the bacterial secretory circular peptide gassericin A, a bacteriocin. The binding of gassericin A to Keratin 19 (KRT19) on the plasma membrane of intestinal epithelial cells was essential for enhancement of fluid absorption and decreased secretion. These findings suggest the use of L. gasseri LA39 and L. frumenti as antibiotic alternatives for preventing diarrhea in mammals.}, }
@article {pmid30541945, year = {2018}, author = {Jayasudha, R and Chakravarthy, SK and Prashanthi, GS and Sharma, S and Garg, P and Murthy, SI and Shivaji, S}, title = {Alterations in gut bacterial and fungal microbiomes are associated with bacterial Keratitis, an inflammatory disease of the human eye.}, journal = {Journal of biosciences}, volume = {43}, number = {5}, pages = {835-856}, pmid = {30541945}, issn = {0973-7138}, mesh = {Adult ; Aspergillus/classification/genetics/isolation &amp; purification ; Case-Control Studies ; Clostridiales/classification/genetics/isolation &amp; purification ; DNA, Bacterial/*genetics/isolation &amp; purification ; DNA, Fungal/*genetics/isolation &amp; purification ; Dysbiosis/diagnosis/*microbiology/pathology ; Faecalibacterium/classification/genetics/isolation &amp; purification ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Keratitis/diagnosis/*microbiology/pathology ; Kluyveromyces/classification/genetics/isolation &amp; purification ; Malassezia/classification/genetics/isolation &amp; purification ; Male ; Megasphaera/classification/genetics/isolation &amp; purification ; Middle Aged ; Mortierella/classification/genetics/isolation &amp; purification ; Rhizopus/classification/genetics/isolation &amp; purification ; Ruminococcus/classification/genetics/isolation &amp; purification ; Veillonellaceae/classification/genetics/isolation &amp; purification ; }, abstract = {Dysbiosis, or imbalance in the gut microbiome, has been implicated in auto-immune, inflammatory, neurological diseases as well as in cancers. More recently it has also been shown to be associated with ocular diseases. In the present study, the association of gut microbiome dysbiosis with bacterial Keratitis, an inflammatory eye disease which significantly contributes to corneal blindness, was investigated. Bacterial and fungal gut microbiomes were analysed using fecal samples of healthy controls (HC, n = 21) and bacterial Keratitis patients (BK, n = 19). An increase in abundance of several antiinflammatory organisms including Dialister, Megasphaera, Faecalibacterium, Lachnospira, Ruminococcus and Mitsuokella and members of Firmicutes, Veillonellaceae, Ruminococcaceae and Lachnospiraceae was observed in HC compared to BK patients in the bacterial microbiome. In the fungal microbiome, a decrease in the abundance of Mortierella, Rhizopus, Kluyveromyces, Embellisia and Haematonectria and an increase in the abundance of pathogenic fungi Aspergillus and Malassezia were observed in BK patients compared to HC. In addition, heatmaps, PCoA plots and inferred functional profiles also indicated significant variations between the HC and BK microbiomes, which strongly suggest dysbiosis in the gut microbiome of BK patients. This is the first study demonstrating the association of gut microbiome with the pathophysiology of BK and thus supports the gut-eye axis hypothesis. Considering that Keratitis affects about 1 million people annually across the globe, the data could be the basis for developing alternate strategies for treatment like use of probiotics or fecal transplantation to restore the healthy microbiome as a treatment protocol for Keratitis.}, }
@article {pmid30525057, year = {2018}, author = {Fang, H and Hua, C and Weiss, S and Liu, A and Cheng, W and Claus, R and Rödel, J and Dirsch, O and Dahmen, U}, title = {Modulation of Innate Immunity by G-CSF and Inflammatory Response by LBPK95A Improves the Outcome of Sepsis in a Rat Model.}, journal = {Journal of immunology research}, volume = {2018}, number = {}, pages = {6085095}, pmid = {30525057}, issn = {2314-7156}, mesh = {Animals ; Disease Models, Animal ; Gene Expression Regulation ; Granulocyte Colony-Stimulating Factor/*immunology ; Humans ; Immunity, Innate ; Inflammation/*immunology ; Interleukin-6/genetics/metabolism ; Lipopolysaccharides/antagonists &amp; inhibitors ; Male ; Neutrophil Infiltration ; Peptides/*immunology/pharmacology ; Rats ; Rats, Inbred Lew ; STAT3 Transcription Factor/metabolism ; Sepsis/*immunology ; Signal Transduction ; Tumor Necrosis Factor-alpha/genetics/metabolism ; }, abstract = {INTRODUCTION: Sepsis is the primary cause of death from infection. We wanted to improve the outcome of sepsis by stimulating innate immunity in combination with modulating the severity of inflammatory responses in rats.<br><br>METHOD: Sepsis was induced by the injection of feces suspension (control). A 5-day course of G-CSF treatment was given before the septic insult (G-CSF). The inflammatory response was decreased using various doses of the LPS-blocking peptide LBPK95A (5&#x2009;mg/kg = 100% Combi group, 0.5&#x2009;mg/kg = 10% Combi group, and 0.05&#x2009;mg/kg = 1% Combi group). Survival rates were observed. Bacterial clearance, neutrophil infiltration, tissue damage, and the induction of hepatic and systemic inflammatory responses were determined 2&#x2009;h and 12&#x2009;h after the septic insult.<br><br>RESULTS: High-dose LBPK95A (100% Combi) reduced the survival rate to 10%, whereas low-dose LBPK95A (10% and 1% Combi) increased the survival rates to 50% and 80%, respectively. The survival rates inversely correlated with multiorgan damage as indicated by the serum levels of ALT and urea. G-CSF treatment increased the white blood cell counts, hepatic neutrophil infiltration, and bacterial clearance in the liver, lung, and blood. The blockade of the LPS-LBP interaction decreased neutrophil infiltration, led to increased white blood cell count, and decreased hepatic neutrophil infiltration, irrespective of dose. However, bacterial clearance improved in the 1% and 10% Combi groups but worsened in the 100% Combi group. G-CSF increased TNF-&#x3b1; and IL-6 levels. Irrespective of dose, the blockade of the LPS-LBP interaction was associated with low systemic cytokine levels and delayed increases in hepatic TNF-&#x3b1; and IL-6 mRNA expression. The delayed increase in cytokines was associated with the phosphorylation of STAT3 and AKT.<br><br>CONCLUSION: Our results revealed that increasing innate immunity by G-CSF pretreatment and decreasing inflammatory responses using LBPK95A improved the survival rates in a rat sepsis model and could be a novel strategy to treat sepsis.}, }
@article {pmid30540788, year = {2018}, author = {Pietri, JE and Tiffany, C and Liang, D}, title = {Disruption of the microbiota affects physiological and evolutionary aspects of insecticide resistance in the German cockroach, an important urban pest.}, journal = {PloS one}, volume = {13}, number = {12}, pages = {e0207985}, pmid = {30540788}, issn = {1932-6203}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Blattellidae/drug effects/*microbiology/physiology ; Feces/microbiology ; Female ; Insecticide Resistance/drug effects ; Insecticides/*metabolism/pharmacology ; Male ; Microbiota/drug effects/*physiology ; Oxazines/*metabolism/pharmacology ; Symbiosis ; }, abstract = {The German cockroach, Blatella germanica, is a common pest in urban environments and is among the most resilient insects in the world. The remarkable ability of the German cockroach to develop resistance when exposed to toxic insecticides is a prime example of adaptive evolution and makes control of this insect an ongoing struggle. Like many other organisms, the German cockroach is host to a diverse community of symbiotic microbes that play important roles in its physiology. In some insect species, there is a strong correlation between the commensal microbial community and insecticide resistance. In particular, several bacteria have been implicated in the detoxification of xenobiotics, including synthetic insecticides. While multiple mechanisms that mediate insecticide resistance in cockroaches have been discovered, significant knowledge gaps still exist in this area of research. Here, we examine the effects of altering the microbiota on resistance to a common insecticide using antibiotic treatments. We describe an indoxacarb-resistant laboratory strain in which treatment with antibiotic increases susceptibility to orally administered insecticide. We further reveal that this strains harbors a gut microbial community that differs significantly from that of susceptible cockroaches in which insecticide resistance is unaffected by antibiotic. More importantly, we demonstrate that transfer of gut microbes from the resistant to the susceptible strain via fecal transplant increases its resistance. Lastly, our data show that antibiotic treatment adversely affects several reproductive life-history traits that may contribute to the dynamics of resistance at the population level. Together these results suggest that the microbiota contributes to both physiological and evolutionary aspects of insecticide resistance and that targeting this community may be an effective strategy to control the German cockroach.}, }
@article {pmid30540704, year = {2019}, author = {Davidovics, ZH and Michail, S and Nicholson, MR and Kociolek, LK and Pai, N and Hansen, R and Schwerd, T and Maspons, A and Shamir, R and Szajewska, H and Thapar, N and de Meij, T and Mosca, A and Vandenplas, Y and Kahn, SA and Kellermayer, R and , }, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection and Other Conditions in Children: A Joint Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {68}, number = {1}, pages = {130-143}, pmid = {30540704}, issn = {1536-4801}, support = {KL2 TR002245/TR/NCATS NIH HHS/United States ; R01 HD081197/HD/NICHD NIH HHS/United States ; UL1 TR000445/TR/NCATS NIH HHS/United States ; }, mesh = {Child ; Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Europe ; Fecal Microbiota Transplantation/*standards ; Gastroenterology/organization &amp; administration/*standards ; Humans ; North America ; Pediatrics/organization &amp; administration/*standards ; *Practice Guidelines as Topic ; Societies, Medical ; }, abstract = {Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.}, }
@article {pmid30539026, year = {2018}, author = {Leustean, AM and Ciocoiu, M and Sava, A and Costea, CF and Floria, M and Tarniceriu, CC and Tanase, DM}, title = {Implications of the Intestinal Microbiota in Diagnosing the Progression of Diabetes and the Presence of Cardiovascular Complications.}, journal = {Journal of diabetes research}, volume = {2018}, number = {}, pages = {5205126}, pmid = {30539026}, issn = {2314-6753}, mesh = {Cardiovascular Diseases/complications/microbiology/*pathology ; Diabetes Mellitus, Type 2/complications/microbiology/*pathology ; Disease Progression ; *Gastrointestinal Microbiome ; Humans ; Insulin Resistance ; }, abstract = {The prevalence of diabetes is steadily rising, and once it occurs, it can cause multiple complications with a negative impact on the whole organism. Complications of diabetes may be macrovascular: such as stroke and ischemic heart disease as well as peripheral vascular and microvascular diseases-retinopathy, nephropathy, and neuropathy. Key factors that cause cardiovascular disease in people with diabetes include hyperglycemia, dyslipidemia, obesity, insulin resistance, inflammation, hypertension, autonomic dysfunction, and decreased vascular response capacity. Microbes can be considered a complex endocrine system capable of ensuring the proper functioning of the body but are also responsible for the development of numerous pathologies (diabetes, coronary syndromes, peripheral arterial disease, neoplasia, Alzheimer's disease, and hepatic steatosis). Changes in the intestinal microbiota may influence the host's sensitivity to insulin, body weight, and lipid and carbohydrate metabolism. Dysbiosis causes activation of proinflammatory mechanisms, metabolic toxicity, and insulin resistance. Trimethylamine N-oxide (TMAO) is a microbial organic compound generated by the large intestine, and its concentration increases in the blood after ingestion of foods rich in L-carnitine and choline, such as red meat, eggs, and fish. The interest for TMAO in cardiometabolic research has recently emerged, given the preclinical evidence that reveals a link between TMAO, diabetes, and cardiovascular complications. Intestinal microbiota can be modulated by changing one's lifestyle but also by antibiotic, probiotic, prebiotic, and fecal transplantation. The purpose of this article is to highlight issues related to the involvement of microbiota and trimethylamine N-oxide in the pathogenesis of diabetes mellitus and cardiovascular disease. Better appreciation of the interactions between food intake and intestinal floral-mediated metabolism can provide clinical insights into the definition of individuals with diabetic risk and cardiometabolic disease as well as potential therapeutic targets for reducing the risk of progression of the disease.}, }
@article {pmid30535609, year = {2018}, author = {Belizário, JE and Faintuch, J}, title = {Microbiome and Gut Dysbiosis.}, journal = {Experientia supplementum (2012)}, volume = {109}, number = {}, pages = {459-476}, doi = {10.1007/978-3-319-74932-7_13}, pmid = {30535609}, issn = {1664-431X}, mesh = {Animals ; Dysbiosis/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Immune System ; Inflammation ; Intestines/microbiology ; }, abstract = {The gastrointestinal (GI) tract is the residence of trillions of microorganisms that include bacteria, archaea, fungi and viruses. The collective genomes of whole microbial communities (microbiota) integrate the gut microbiome. Up to 100 genera and 1000 distinct bacterial species were identified in digestive tube niches. Gut microbiomes exert permanent pivotal functions by promoting food digestion, xenobiotic metabolism and regulation of innate and adaptive immunological processes. Proteins, peptides and metabolites released locally and at distant sites trigger many cell signalling and pathways. This intense crosstalk maintains the host-microbial homeostasis. Diet, age, diet, stress and diseases cause increases or decreases in relative abundance and diversity bacterial specie of GI and other body sites. Studies in animal models and humans have shown that a persistent imbalance of gut's microbial community, named dysbiosis, relates to inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), diabetes, obesity, cancer, cardiovascular and central nervous system disorders. Notably specific bacterial communities are promising clinical target to treat inflammatory and infectious diseases. In this context, intestinal microbiota transplantation (IMT) is one optional treatment for IBD, in particular to patients with recurrent Clostridium difficile-induced pseudo-membrane colitis. Here we discuss on recent discoveries linking whole gut microbiome dysbiosis to metabolic and inflammatory diseases and potential prophylactic and therapeutic applications of faecal and phage therapy, probiotic and prebiotic diets.}, }
@article {pmid30535376, year = {2019}, author = {Sakaguchi, Y and Hamano, T and Matsui, I and Oka, T and Yamaguchi, S and Kubota, K and Shimada, K and Matsumoto, A and Hashimoto, N and Isaka, Y}, title = {Low magnesium diet aggravates phosphate-induced kidney injury.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {34}, number = {8}, pages = {1310-1319}, doi = {10.1093/ndt/gfy358}, pmid = {30535376}, issn = {1460-2385}, mesh = {Animals ; Diet/*adverse effects ; Fibroblast Growth Factor-23 ; Fibroblast Growth Factors/blood ; Glucuronidase/metabolism ; Kidney Diseases/blood/etiology/*pathology ; Magnesium/*administration &amp; dosage/blood ; Male ; Mice ; Mice, Inbred C57BL ; Parathyroid Hormone/blood ; Phosphates/blood/*toxicity ; }, abstract = {BACKGROUND: Magnesium is known to protect against phosphate-induced tubular cell injuries in vitro. We investigated in vivo effects of magnesium on kidney injuries and phosphate metabolism in mice exposed to a high phosphate diet.<br><br>METHODS: Heminephrectomized mice were maintained on a high phosphate/normal magnesium diet or a high phosphate/low magnesium diet for 6&#x2009;weeks. We compared renal histology, phosphaturic hormones and renal &#x3b1;-Klotho expression between the two diet groups.<br><br>RESULTS: High phosphate diet-induced tubular injuries and interstitial fibrosis were remarkably aggravated by the low-magnesium diet. At 1&#x2009;week after high phosphate feeding when serum creatinine levels were similar between the two groups, the low magnesium diet suppressed not only fecal phosphate excretion but also urinary phosphate excretion, resulting in increased serum phosphate levels. Parathyroid hormone (PTH) levels were not appropriately elevated in the low magnesium diet group despite lower 1,25-dihydroxyvitamin D and serum calcium levels compared with the normal magnesium diet group. Although fibroblast growth factor 23 (FGF23) levels were lower in the low magnesium diet group, calcitriol-induced upregulation of FGF23 could not restore the impaired urinary phosphate excretion. The low magnesium diet markedly downregulated &#x3b1;-Klotho expression in the kidney. This downregulation of &#x3b1;-Klotho occurred even when mice were fed the low phosphate diet.<br><br>CONCLUSIONS: A low magnesium diet aggravated high phosphate diet-induced kidney injuries. Impaired PTH secretion and downregulation of renal &#x3b1;-Klotho were likely to be involved in the blunted urinary phosphate excretion by the low magnesium diet. Increasing dietary magnesium may be useful to attenuate phosphate-induced kidney injury.}, }
@article {pmid30534963, year = {2019}, author = {Kalla, R and Pitt, M and Sharma, A}, title = {The Role of Autologous Fecal Microbiota Transplantation in Diversion Colitis: A Case Report.}, journal = {Inflammatory bowel diseases}, volume = {25}, number = {4}, pages = {e29-e30}, doi = {10.1093/ibd/izy270}, pmid = {30534963}, issn = {1536-4844}, mesh = {Colitis/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Humans ; Middle Aged ; Treatment Outcome ; }, }
@article {pmid30534859, year = {2018}, author = {Quera, R and Ibáñez, P and Simian, D and Rivera, D and Acuña, G and Espinoza, R}, title = {[Fecal microbiota transplantation through colonoscopy for Clostridium difficile recurrent infection. Report of eight cases].}, journal = {Revista medica de Chile}, volume = {146}, number = {8}, pages = {823-830}, doi = {10.4067/s0034-98872018000800823}, pmid = {30534859}, issn = {0717-6163}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/classification/therapeutic use ; Clostridioides difficile ; Clostridium Infections/*therapy ; *Colonoscopy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Most cases of Clostridium difficile infection (CDI) respond to a standard course of antibiotics, however recurrent CDI is becoming common and alternative therapeutic strategies are needed. In this scenario, fecal microbiota transplantation (FMT) has been suggested.<br><br>AIM: To describe the efficacy and safety of FMT for the treatment of recurrent CDI.<br><br>PATIENTS AND METHODS: Review of medical records of all patients with recurrent CDI treated with FMT between April 2013 and April 2017. Demographic and clinical data were abstracted including details of treatment prior to FMT, rate of FMT treatment success and clinical course during follow-up period. Telephone surveys were conducted to determine patient satisfaction.<br><br>RESULTS: Eight patients aged 19 to 82 years (six women) underwent FMT. They experienced a median of four previous episodes of CDI (range 3-8). The mean duration of CDI was 18 days (range 3-36) before FMT. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 100%. During the follow-up period (median 24 months, range 7-55), two patients developed CDI, one of them after using antibiotics. Adverse events were reported in three patients. Two had bloating and one patient with Crohn's disease and a history of bacteremia had an episode of Escherichia coli bacteremia. All patients would use FMT again if necessary.<br><br>CONCLUSIONS: FMT through colonoscopy appears to be a safe, effective and long-lasting therapy in cases of recurrent CDI.}, }
@article {pmid30534630, year = {2018}, author = {Lindheim, L and Manti, M and Fornes, R and Bashir, M and Czarnewski, P and Diaz, OE and Seifert, M and Engstrand, L and Villablanca, EJ and Obermayer-Pietsch, B and Stener-Victorin, E}, title = {Reproductive and Behavior Dysfunction Induced by Maternal Androgen Exposure and Obesity Is Likely Not Gut Microbiome-Mediated.}, journal = {Journal of the Endocrine Society}, volume = {2}, number = {12}, pages = {1363-1380}, pmid = {30534630}, issn = {2472-1972}, abstract = {Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder of unclear etiology in women and is characterized by androgen excess, insulin resistance, and mood disorders. The gut microbiome is known to influence conditions closely related with PCOS, and several recent studies have observed changes in the stool microbiome of women with PCOS. The mechanism by which the gut microbiome interacts with PCOS is still unknown. We used a mouse model to investigate if diet-induced maternal obesity and maternal DHT exposure, mimicking the lean and obese PCOS women, cause lasting changes in the gut microbiome of offspring. Fecal microbiome profiles were assessed using Illumina paired-end sequencing of 16S rRNA gene V4 amplicons. We found sex-specific effects of maternal and offspring diet, and maternal DHT exposure on fecal bacterial richness and taxonomic composition. Female offspring exposed to maternal obesity and DHT displayed reproductive dysfunction and anxietylike behavior. Fecal microbiota transplantation from DHT and diet-induced obesity exposed female offspring to wild-type mice did not transfer reproductive dysfunction and did not cause the expected increase in anxietylike behavior in recipients. Maternal obesity and androgen exposure affect the gut microbiome of offspring, but the disrupted estrous cycles and anxietylike behavior are likely not microbiome-mediated.}, }
@article {pmid30531472, year = {2019}, author = {Jama, HA and Kaye, DM and Marques, FZ}, title = {The gut microbiota and blood pressure in experimental models.}, journal = {Current opinion in nephrology and hypertension}, volume = {28}, number = {2}, pages = {97-104}, doi = {10.1097/MNH.0000000000000476}, pmid = {30531472}, issn = {1473-6543}, mesh = {Animals ; Blood Pressure ; Diet ; Dietary Supplements ; *Disease Models, Animal ; Dysbiosis/*complications/therapy ; *Gastrointestinal Microbiome ; *Germ-Free Life ; Humans ; Hypertension/drug therapy/*microbiology/physiopathology ; Models, Theoretical ; }, abstract = {PURPOSE OF REVIEW: To summarize evidence supporting that microorganisms colonizing our gastrointestinal tract, collectively known as the gut microbiota, are implicated in the development and maintenance of hypertension in experimental models.<br><br>RECENT FINDINGS: The use of gnotobiotic (germ-free) mice has been essential for advancement in this area: they develop higher blood pressure (BP) if they receive faecal transplants from hypertensive patients compared to normotensive donors, and germ-free mice have a blunted response to angiotensin II. Experimental hypertension is consistently accompanied by changes in the composition of the gut microbiota. This is combined with a shift in microbial diversity and the deterioration of the gut epithelial barrier commonly referred to as gut dysbiosis. Restoration of normal gut biosis and microbiota alleviates and protects against the development of hypertension in both genetic and pharmacological models. This has been achieved by the use of antibiotics, faecal transplants between normotensive and hypertensive strains, and the use of prebiotics (i.e. food stuff that feeds the microbiota), probiotics (i.e. live bacteria) and gut metabolites (i.e. short-chain fatty acids).<br><br>SUMMARY: Research into experimental hypertension supports that the gut microbiota contributes to the regulation of BP. Manipulation of the microbiota might represent a new tool to prevent hypertension.}, }
@article {pmid30531266, year = {2019}, author = {Chandra, A and Mishra, B and Kumar, S and Chopra, N and Gupta, V and Dangi, A and Gorla, PK and Gupta, V}, title = {Composite Antropyloric Valve and Gluteus Maximus Muscle Wrap for Neoanal Reconstruction: Initial Results.}, journal = {Diseases of the colon and rectum}, volume = {62}, number = {1}, pages = {104-111}, doi = {10.1097/DCR.0000000000001232}, pmid = {30531266}, issn = {1530-0358}, mesh = {Adolescent ; Adult ; Anal Canal/*surgery ; Buttocks ; Fecal Incontinence/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*surgery ; Prospective Studies ; Pyloric Antrum/*transplantation ; Plastic Surgery Procedures/*methods ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Severe fecal incontinence has a significant negative impact on patient well-being. Current surgical methods of total anorectal reconstruction to substitute a colostomy have suboptimal results. A composite graft using antropyloric valve transposition and gracilis wrap has been described with good outcomes. However, this procedure requires extensive training of patients. Gluteus maximus, an accessory muscle for continence, may be better suited for this purpose.<br><br>OBJECTIVE: The purpose of this study was to evaluate the outcomes of composite antropylorus-gluteus graft for intractable fecal incontinence.<br><br>DESIGN: Patients underwent a 3-stage procedure: antropyloric transposition with diversion stoma followed by gluteus wrap. Stoma was closed after ensuring the anatomic and functional integrity of the graft.<br><br>SETTINGS: This study was conducted at a single tertiary care institution.<br><br>PATIENTS: Patients who were on permanent colostomy for intractable incontinence or would have had one after abdominoperineal resection were included.<br><br>MAIN OUTCOME MEASURES: Endoultrasonography, MRI, loopogram, saline holding test, anal manometry, St. Mark's fecal incontinence score, and personal interviews were used for measurement.<br><br>RESULTS: Eleven patients underwent the procedure with a median follow-up of 16 months (range, 13-34 mo). Digital rectal examination revealed a resting tone with a distinct squeeze provided by the composite graft. Radiological imaging confirmed healthy grafts. There was a significant improvement in mean anal manometry values (resting pressure: preoperative = 10.25 mm Hg vs postoperative = 20.45 mm Hg; squeeze pressure: preoperative = 22.63 mm Hg vs postoperative = 105.18 mm Hg) and mean incontinence score postprocedure (preoperative = 22.8 vs postoperative = 8.6). On personal interview, majority of the patients were continent and expressed satisfaction with the procedure.<br><br>LIMITATIONS: The study was limited by its small sample size with no control group.<br><br>CONCLUSIONS: Composite graft in patients with intractable fecal incontinence can serve as a viable novel method for total anorectal reconstruction. However, it should only be recommended for a highly select group of individuals in a surveillance setting. Its long-term outcomes remain to be determined as well as its risk versus benefit.}, }
@article {pmid30529583, year = {2019}, author = {Paramsothy, S and Nielsen, S and Kamm, MA and Deshpande, NP and Faith, JJ and Clemente, JC and Paramsothy, R and Walsh, AJ and van den Bogaerde, J and Samuel, D and Leong, RWL and Connor, S and Ng, W and Lin, E and Borody, TJ and Wilkins, MR and Colombel, JF and Mitchell, HM and Kaakoush, NO}, title = {Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis.}, journal = {Gastroenterology}, volume = {156}, number = {5}, pages = {1440-1454.e2}, doi = {10.1053/j.gastro.2018.12.001}, pmid = {30529583}, issn = {1528-0012}, mesh = {Bacteria/classification/genetics/growth &amp; development/*metabolism ; Biomarkers/metabolism ; Colitis, Ulcerative/diagnosis/microbiology/*therapy ; Double-Blind Method ; Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Metabolomics ; New South Wales ; Remission Induction ; Ribotyping ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized controlled trial of FMT in patients with active UC, we aimed to identify bacterial taxonomic and functional factors associated with response to therapy.<br><br>METHODS: We performed a double-blind trial of 81 patients with active UC randomly assigned to groups that received an initial colonoscopic infusion and then intensive multidonor FMT or placebo enemas, 5 d/wk for 8 weeks. Patients in the FMT group received blended homogenized stool from 3-7 unrelated donors. Patients in the placebo group were eligible to receive open-label FMT after the double-blind study period. We collected 314 fecal samples from the patients at screening, every 4 weeks during treatment, and 8 weeks after the blinded or open-label FMT therapy. We also collected 160 large-bowel biopsy samples from the patients at study entry, at completion of 8 weeks of blinded therapy, and at the end of open-label FMT, if applicable. We analyzed 105 fecal samples from the 14 individual donors (n&#xa0;= 55), who in turn contributed to 21 multidonor batches (n&#xa0;= 50). Bacteria in colonic and fecal samples were analyzed by both 16S ribosomal RNA gene and transcript amplicon sequencing; 285 fecal samples were analyzed by shotgun metagenomics, and 60 fecal samples were analyzed for metabolome features.<br><br>RESULTS: FMT increased microbial diversity and altered composition, based on analyses of colon and fecal samples collected before vs after FMT. Diversity was greater in fecal and colon samples collected before and after FMT treatment from patients who achieved remission compared with patients who did not. Patients in remission after FMT had enrichment of Eubacterium hallii and Roseburia inulivorans compared with patients who did not achieve remission after FMT and had increased levels of short-chain fatty acid biosynthesis and secondary bile acids. Patients who did not achieve remission had enrichment of Fusobacterium gonidiaformans, Sutterella wadsworthensis, and Escherichia species and increased levels of heme and lipopolysaccharide biosynthesis. Bacteroides in donor stool were associated with remission in patients receiving FMT, and Streptococcus species in donor stool was associated with no response to FMT.<br><br>CONCLUSIONS: In an analysis of fecal and colonic mucosa samples from patients receiving FMT for active UC and stool samples from donors, we associated specific bacteria and metabolic pathways with induction of remission. These findings may be of value in the design of microbe-based therapies for UC. ClinicalTrials.gov, Number NCT01896635.}, }
@article {pmid30529117, year = {2019}, author = {Papanicolas, LE and Wang, Y and Choo, JM and Gordon, DL and Wesselingh, SL and Rogers, GB}, title = {Optimisation of a propidium monoazide based method to determine the viability of microbes in faecal slurries for transplantation.}, journal = {Journal of microbiological methods}, volume = {156}, number = {}, pages = {40-45}, doi = {10.1016/j.mimet.2018.12.001}, pmid = {30529117}, issn = {1872-8359}, mesh = {Analytic Sample Preparation Methods/*methods ; Azides/chemistry ; Bacterial Load ; Escherichia coli/*isolation &amp; purification ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; *Microbial Viability ; Propidium/analogs &amp; derivatives/chemistry ; Pseudomonas/*isolation &amp; purification ; Specimen Handling ; Staphylococcus/*isolation &amp; purification ; }, abstract = {The efficacy of faecal microbiota transplantation (FMT) as a therapeutic intervention may depend on the viability of the microorganisms in faecal slurries (FS) prepared from donor stool. However, determining the viability of these organisms is challenging. Most microorganisms in stool are refractory to culture using standard techniques, and culture-independent PCR-based methods derive signal from both viable and non-viable cells. Propidium monoazide (PMA) treatment has been shown to be effective in preventing PCR amplification of DNA from non-viable bacteria in a range of contexts. However, this methodology can be sensitive to factors such as bacterial load and sample turbidity. We describe the optimisation of a PMA treatment methodology for FS that restricts quantitative PCR-based bacterial enumeration to viable cells. When applied to concentrated FS (10-25% stool content), PMA treatment at 100 μM concentration was ineffective in preventing DNA amplification from heat-killed cells. Efficacy was not significantly improved by doubling the PMA concentration. However, PMA treatment efficacy was improved markedly following 10-fold sample dilution, and was found to be optimal at 100-fold dilution. Substantial reductions in viable bacterial load could be observed following both freeze-thaw and heat-treatment of FS. This method successfully prevented DNA amplification of heat-killed Pseudomonas and Staphylococcus spiked into stool and could reliably determine the proportion of live bacteria and viable E. coli counts present in fresh and heat-treated stool. With appropriate sample dilution, PMA treatment excluded >97% of non-viable cells from amplification in all assays, without significantly affecting the amplification of DNA from viable cells. This method can be applied to optimise sample processing of FMT donor material, and to characterise bacterial viability within faecal samples more widely.}, }
@article {pmid30528446, year = {2019}, author = {Ciaccio, C and Saletti, V and D'Arrigo, S and Esposito, S and Alfei, E and Moroni, I and Tonduti, D and Chiapparini, L and Pantaleoni, C and Milani, D}, title = {Clinical spectrum of PTEN mutation in pediatric patients. A bicenter experience.}, journal = {European journal of medical genetics}, volume = {62}, number = {12}, pages = {103596}, doi = {10.1016/j.ejmg.2018.12.001}, pmid = {30528446}, issn = {1878-0849}, mesh = {Autism Spectrum Disorder/*genetics/pathology ; Cardiovascular Abnormalities/*genetics/pathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Megalencephaly/*genetics/pathology ; *Mutation ; PTEN Phosphohydrolase/*genetics ; *Phenotype ; Syndrome ; }, abstract = {OBJECTIVE OF THE STUDY: To give a full overview of the clinical presentation of PTEN mutations in pediatric patients and to propose a pediatric follow-up protocol.<br><br>METHODS: Recruitment of 16 PTEN mutated children (age 6 months-11 years) from two pediatric centers in Milan (Italy) between 2006 and 2017. All the patients underwent clinical and neurologic evaluations, cognitive and behavioral tests, and brain MRI; they are currently following an oncologic follow-up.<br><br>RESULTS: Extreme macrocephaly is present in all the patients (69% HC above +4 SD). Neuropsychiatric issues have high prevalence, with 56% of patients showing developmental delay and 25% showing autism spectrum disorder. Brain MRI reveals in 75% of the patients at least one of the following: enlarged perivascular spaces, white matter anomalies, and/or downward displacement of the cerebellar tonsils through the foramen magnum, resulting in Chiari I malformation in two patients. Vascular malformations have a prevalence of 19%, with further evidence that complex cardiovascular malformations may be related to PTEN mutations; 31% of patients present hamartomas. None of our patients have so far experienced any oncologic complication.<br><br>CONCLUSIONS: We suggest to screen for PTEN mutations all children presenting macrocephaly and one of the following: neurodevelopmental issues, one of the three major brain MRI anomalies, cutaneous lesions, vascular malformations, family history positive for PTEN related malignancies; or also with macrocephaly alone when exceeding +3 SD. Basing on our cohort results and further recent studies on the condition, we recommend a follow-up protocol that includes annual clinical and dermatological examination, thyroid and abdominal US, and Fecal Occult Blood test plus neurodevelopmental evaluation, heart US (to exclude congenital heart malformations), and brain MRI (to exclude Chiari I malformation) at diagnosis.}, }
@article {pmid30526683, year = {2018}, author = {Draper, LA and Ryan, FJ and Smith, MK and Jalanka, J and Mattila, E and Arkkila, PA and Ross, RP and Satokari, R and Hill, C}, title = {Long-term colonisation with donor bacteriophages following successful faecal microbial transplantation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {220}, pmid = {30526683}, issn = {2049-2618}, mesh = {Bacteriophages/*classification/isolation &amp; purification ; Clostridium Infections/*therapy/virology ; Fecal Microbiota Transplantation/*methods ; Feces/virology ; Humans ; Metagenomics ; Phylogeny ; Tissue Donors ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is used in the treatment of recurrent Clostridium difficile infection. Its success is typically attributed to the restoration of a diverse microbiota. Viruses (including bacteriophages) are the most numerically dominant and potentially the most diverse members of the microbiota, but their fate following FMT has not been well studied.<br><br>RESULTS: We studied viral transfer following FMT from 3 donors to 14 patients. Recipient viromes resembled those of their donors for up to 12&#x2009;months. Tracking individual bacteriophage colonisation revealed that engraftment of individual bacteriophages was dependent on specific donor-recipient pairings. Specifically, multiple recipients from a single donor displayed highly individualised virus colonisation patterns.<br><br>CONCLUSIONS: The impact of viruses on long-term microbial dynamics is a factor that should be reviewed when considering FMT as a therapeutic option.}, }
@article {pmid30525949, year = {2019}, author = {Wing, AC and Kremenchutzky, M}, title = {Multiple sclerosis and faecal microbiome transplantation: are you going to eat that?.}, journal = {Beneficial microbes}, volume = {10}, number = {1}, pages = {27-32}, doi = {10.3920/BM2018.0029}, pmid = {30525949}, issn = {1876-2891}, mesh = {Dysbiosis/immunology/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Host Microbial Interactions/immunology ; Humans ; Intestines/immunology/microbiology ; Multiple Sclerosis/immunology/microbiology/*therapy ; Probiotics/therapeutic use ; }, abstract = {Gut microbiome interaction goes beyond commensal function as vitamin production or support nutrients digestion. It also interplays with the host immune system and may be related to the development of immune-mediated diseases. Multiple sclerosis patients have dysbiosis compared to healthy individuals. But how this relates to disease development and severity is still uncertain. Dietary change including probiotic mixtures or ketogenic regimen has proven to change microbiome in multiple sclerosis (MS) subjects to one similar to healthy controls. However, proof of clinical benefits is lacking. We dissert on current knowledge about immune system and gut bacteria interactions. We discuss faecal microbial transplantation as a potential intervention to ameliorate gut dysbiosis in MS as well as the caveats of a clinical trial design.}, }
@article {pmid30521978, year = {2019}, author = {Huang, C and Yang, X and Zeng, B and Zeng, L and Gong, X and Zhou, C and Xia, J and Lian, B and Qin, Y and Yang, L and Liu, L and Xie, P}, title = {Proteomic analysis of olfactory bulb suggests CACNA1E as a promoter of CREB signaling in microbiota-induced depression.}, journal = {Journal of proteomics}, volume = {194}, number = {}, pages = {132-147}, doi = {10.1016/j.jprot.2018.11.023}, pmid = {30521978}, issn = {1876-7737}, mesh = {Animals ; Calcium Channels, R-Type/*metabolism ; Cation Transport Proteins/*metabolism ; Cyclic AMP Response Element-Binding Protein/*metabolism ; *Depression/metabolism/microbiology/pathology ; *Gastrointestinal Microbiome ; *Gene Expression Regulation ; *Germ-Free Life ; Mice ; Olfactory Bulb/*metabolism/pathology ; Proteomics ; *Signal Transduction ; }, abstract = {Major depressive disorders impact approximately 17% of the population worldwide, whose high morbidity and considerable adversity have resulted in enormous social and economic burden. In addition, clinically depressed patients often show reduced volume of olfactory bulb (OB) and decreased olfactory sensitivity. Although mounting evidence conveyed that the gut microbiota may implicate the pathophysiology of major depressive disorder (MDD) via the microbe-gut-brain axis, knowledge about its distinctive molecular mechanism is rudimentary. Herein, iTRAQ coupled with LC-MS/MS was applied to compare the OB proteome between "pathological microbiota" and "healthy microbiota" germ-free mice. A set of 367 proteins were differentially identified in the OB, including 119 up-regulated and 248 down-regulated proteins compared with the levels in controls. A combined analysis with significantly changed OB proteins from CUMS depression model supported the role of CREB signaling, whose dysregulation is likely to disrupt the axonogenesis of OB under microbiota condition. With that, the down-regulated CACNA1E and its downstream proteins (CALM/ CaMKII/ CREB/ BDNF) in CREB pathway were validated by Western blot. Meanwhile, the canonical pathways involved Nuclear Receptor Signaling highlighted the fecal microbiota transplantation (FMT) model, which would be a new breakthrough for depressive research. These findings enrich the previous research achievements about the gut microbiota in psychiatric disorders, providing a creative insight into the intricate mechanisms of OB dysfunction in depression. SIGNIFICANCE: Emerging evidence has shown that gut microbiota can greatly influence brain functions and even behaviors. As one of the post-developmental neurogenesis areas for the adult brain, the OB is becoming increasingly important in the study of the pathogenesis of depression. Using an iTRAQ-based proteomics, we identified 367 altered proteins in the OB of fecal microbiota transplanted mouse, which provide a novel insight for further research of the "microbiota-gut-brain axis". In addition, combined analyses with the CUMS depression model and the validation of key proteins by Western blot may assist in the investigation of OB dysfunction in mental sickness.}, }
@article {pmid30521856, year = {2019}, author = {Kaako, A and Al-Amer, M and Abdeen, Y}, title = {Bezlotoxumab use as adjunctive therapy with the third fecal microbiota transplant in refractory recurrent Clostridium difficile colitis; a case report and concise literature review.}, journal = {Anaerobe}, volume = {55}, number = {}, pages = {112-116}, doi = {10.1016/j.anaerobe.2018.11.010}, pmid = {30521856}, issn = {1095-8274}, mesh = {Antibodies, Monoclonal/*administration &amp; dosage ; Antibodies, Neutralizing/*administration &amp; dosage ; Antitoxins/*administration &amp; dosage ; Broadly Neutralizing Antibodies ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*therapy ; Combined Modality Therapy/methods ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Middle Aged ; Treatment Outcome ; }, abstract = {Clostridium difficile is the most commonly reported pathogen to cause nosocomial infections in the United States with a high burden affecting morbidity, mortality and healthcare expenditure. The use of Fecal Microbiota Transplantation (FMT) is one of the current standard therapies for recurrent C. difficile infection (CDIr). One emerging promising approach is the use of monoclonal antibodies that bind to and neutralize C. difficile toxins such as Bezlotoxumab. We present the first case report on combining the third FMT with bezlotoxumab after the failure of standard-of-care antibiotics and two trials of FMT alone, with subsequent success in preventing the recurrence of refractory CDI for 12 weeks following treatment. This case highlights the need for further studies and guidelines to recommend the best combination among different treatment options and modalities.}, }
@article {pmid30519847, year = {2019}, author = {Allegretti, JR and Fischer, M and Sagi, SV and Bohm, ME and Fadda, HM and Ranmal, SR and Budree, S and Basit, AW and Glettig, DL and de la Serna, EL and Gentile, A and Gerardin, Y and Timberlake, S and Sadovsky, R and Smith, M and Kassam, Z}, title = {Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose.}, journal = {Digestive diseases and sciences}, volume = {64}, number = {6}, pages = {1672-1678}, pmid = {30519847}, issn = {1573-2568}, mesh = {Adult ; Aged ; Aged, 80 and over ; Capsules ; Clostridium Infections/diagnosis/microbiology/*therapy ; Colon/*microbiology ; Fecal Microbiota Transplantation/adverse effects/*instrumentation ; Female ; *Gastrointestinal Microbiome ; Humans ; Hydrogen-Ion Concentration ; Male ; Middle Aged ; Remission Induction ; Stomach/*microbiology ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium. difficile infection (rCDI). FMT capsules have emerged, and it is unknown if delivery location and dose impact efficacy.<br><br>METHODS: We compared two cohorts of patients receiving two capsule formulations: gastric release (FMTgr) and targeted colonic release (FMTcr) at two different sites. Cohort A received FMTgr at (1) high dose: 60 capsules and low dose: 30 capsules. Patients in Cohort B received FMTcr at (1) high dose: 30 capsules (2) low dose: 10 capsules. Clinical cure rates and adverse events were monitored through week 8. Paired t-tests were used to compare diversity pre- and post-FMT.<br><br>RESULTS: 51 rCDI patients were enrolled. Cohort A contained n&#x2009;=&#x2009;20 and Cohort B contained n&#x2009;=&#x2009;31. Overall cure at week 8 for FMTgr was 75% (15/20) compared to 80.6% for FMTcr, (25/31), p&#x2009;=&#x2009;0.63. Both formulations were safe with no serious adverse events. FMTcr was superior at increasing gut microbial diversity.<br><br>DISCUSSION: To our knowledge, this is the first study to compare targeted delivery of FMT capsules. While both capsules were safe and efficacious, microbial engraftment patterns were superior in FMTcr.}, }
@article {pmid30519748, year = {2019}, author = {Zhu, Y and He, C and Li, X and Cai, Y and Hu, J and Liao, Y and Zhao, J and Xia, L and He, W and Liu, L and Luo, C and Shu, X and Cai, Q and Chen, Y and Lu, N}, title = {Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice.}, journal = {Journal of gastroenterology}, volume = {54}, number = {4}, pages = {347-358}, pmid = {30519748}, issn = {1435-5922}, support = {81760120//National Natural Science Foundation of China/ ; 81460116//National Natural Science Foundation of China/ ; 20171BBG70084//Science and Technology Department of Jiangxi Province/ ; }, mesh = {Acute Disease ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Case-Control Studies ; Cytokines/blood ; Disease Models, Animal ; Dysbiosis/*complications ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Pancreatitis/microbiology/*physiopathology ; RNA, Ribosomal, 16S/genetics ; Severity of Illness Index ; Young Adult ; }, abstract = {BACKGROUND: The gut is implicated in the pathogenesis of acute pancreatitis (AP) and the infectious complications of AP are commonly associated with enteric bacteria, yet whether gut microbiota dysbiosis participants in AP severity remains largely unknown.<br><br>METHODS: We collected clinical information and fecal samples from 165 adult participants, including 41 with mild AP (MAP), 59 with moderately severe AP (MSAP), 30 with severe AP (SAP) and 35 healthy controls (HC). The serum inflammatory cytokines and gut barrier indexes were detected. Male C57BL/6 mice with AP were established and injuries of pancreas were evaluated in antibiotic-treated mice, germ-free mice as well as those transplanted with fecal microbiota. The gut microbiota was analyzed by 16S rRNA gene sequencing.<br><br>RESULTS: The structure of gut microbiota was significantly different between AP and HC, and the disturbed microbiota was closely correlated with systematic inflammation and gut barrier dysfunction. Notably, the microbial composition changed further with the worsening of AP and the abundance of beneficial bacteria such as Blautia was decreased in SAP compared with MAP and MSAP. The increased capacity for the inferred pathway, bacterial invasion of epithelial cells in AP, highly correlated with the abundance of Escherichia-Shigella. Furthermore, the antibiotic-treated mice and germ-free mice exhibited alleviated pancreatic injury after AP induction and subsequent fecal microbiota transplantation in turn exacerbated the disease.<br><br>CONCLUSIONS: This study identifies the gut microbiota as an important mediator during AP and its dysbiosis is associated with AP severity, which suggests its role as potential therapeutic target.}, }
@article {pmid30518790, year = {2018}, author = {Burrello, C and Garavaglia, F and Cribiù, FM and Ercoli, G and Lopez, G and Troisi, J and Colucci, A and Guglietta, S and Carloni, S and Guglielmetti, S and Taverniti, V and Nizzoli, G and Bosari, S and Caprioli, F and Rescigno, M and Facciotti, F}, title = {Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {5184}, pmid = {30518790}, issn = {2041-1723}, mesh = {Adaptive Immunity ; Animals ; Antigen-Presenting Cells/immunology ; CD4-Positive T-Lymphocytes/immunology ; Colitis/genetics/immunology/microbiology/*therapy ; Dendritic Cells/immunology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Immunity, Innate ; Interleukin-10/genetics/*immunology ; Intestinal Mucosa/*immunology/*microbiology ; Macrophages/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Natural Killer T-Cells/immunology ; }, abstract = {Alteration of the gut microbiota has been associated with different gastrointestinal disorders. Normobiosis restoration by faecal microbiota transplantation (FMT) is considered a promising therapeutic approach, even if the mechanisms underlying its efficacy are at present largely unknown. Here we sought to elucidate the functional effects of therapeutic FMT administration during experimental colitis on innate and adaptive immune responses in the intestinal mucosa. We show that therapeutic FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the simultaneous activation of different immune-mediated pathways, ultimately leading to IL-10 production by innate and adaptive immune cells, including CD4[+] T cells, iNKT cells and Antigen Presenting Cells (APC), and reduces the ability of dendritic cells, monocytes and macrophages to present MHCII-dependent bacterial antigens to colonic T cells. These results demonstrate the capability of FMT to therapeutically control intestinal experimental colitis and poses FMT as a valuable therapeutic option in immune-related pathologies.}, }
@article {pmid30518356, year = {2018}, author = {Bin, P and Tang, Z and Liu, S and Chen, S and Xia, Y and Liu, J and Wu, H and Zhu, G}, title = {Intestinal microbiota mediates Enterotoxigenic Escherichia coli-induced diarrhea in piglets.}, journal = {BMC veterinary research}, volume = {14}, number = {1}, pages = {385}, pmid = {30518356}, issn = {1746-6148}, mesh = {Animals ; Bacteria/classification/genetics ; Diarrhea/microbiology/*veterinary ; Dysbiosis/immunology/microbiology/*veterinary ; Enterotoxigenic Escherichia coli/immunology/physiology ; Escherichia coli Infections/veterinary ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*genetics/*immunology ; Intestinal Diseases/immunology/microbiology/*veterinary ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; Swine ; Swine Diseases/immunology/*microbiology ; }, abstract = {BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in humans, cows, and pigs. The gut microbiota underlies pathology of several infectious diseases yet the role of the gut microbiota in the pathogenesis of ETEC-induced diarrhea is unknown.<br><br>RESULTS: By using an ETEC induced diarrheal model in piglet, we profiled the jejunal and fecal microbiota using metagenomics and 16S rRNA sequencing. A jejunal microbiota transplantation experiment was conducted to determine the role of the gut microbiota in ETEC-induced diarrhea. ETEC-induced diarrhea influenced the structure and function of gut microbiota. Diarrheal piglets had lower Bacteroidetes: Firmicutes ratio and microbiota diversity in the jejunum and feces, and lower percentage of Prevotella in the feces, but higher Lactococcus in the jejunum and higher Escherichia-Shigella in the feces. The transplantation of the jejunal microbiota from diarrheal piglets to uninfected piglets leaded to diarrhea after transplantation. Microbiota transplantation experiments also supported the notion that dysbiosis of gut microbiota is involved in the immune responses in ETEC-induced diarrhea.<br><br>CONCLUSION: We conclude that ETEC infection influences the gut microbiota and the dysbiosis of gut microbiota after ETEC infection mediates the immune responses in ETEC infection.}, }
@article {pmid30518033, year = {2018}, author = {Huang, E and Kang, S and Park, H and Park, S and Ji, Y and Holzapfel, WH}, title = {Differences in Anxiety Levels of Various Murine Models in Relation to the Gut Microbiota Composition.}, journal = {Biomedicines}, volume = {6}, number = {4}, pages = {}, pmid = {30518033}, issn = {2227-9059}, abstract = {Psychobiotics are probiotic strains that confer mental health benefits to the host through the modulation of the gut microbial population. Mounting evidence shows that the gut microbiota play an important role in communication within the gut[-]brain axis. However, the relationship between the host genetics and the gut microbiota and their influence on anxiety are still not fully understood. Hence, in our research, we attempted to draw a connection between host genetics, microbiota composition, and anxiety by performing an elevated plus maze (EPM) test on four genetically different mice. Four different breeds of 5-week-old mice were used in this experiment: Balb/c, Orient C57BL/6N, Taconic C57BL/6N, and Taconic C57BL/6J. After 1 week of adaptation, their initial anxiety level was monitored using the EPM test via an EthoVision XT, a standardized software used for behavorial testing. Significant differences in the initial anxiety level and microbial composition were detected. Subsequently, the microbiota of each group was modulated by the administration of either a probiotic, fecal microbiota transplantation, or antibiotics. Changes were observed in host anxiety levels in correlation to the shift of the gut microbiota. Our results suggest that the microbiota, host genetics, and psychological symptoms are strongly related, yet the deeper mechanistic links need further exploration.}, }
@article {pmid30508676, year = {2019}, author = {Hu, XF and Zhang, WY and Wen, Q and Chen, WJ and Wang, ZM and Chen, J and Zhu, F and Liu, K and Cheng, LX and Yang, J and Shu, YW}, title = {Fecal microbiota transplantation alleviates myocardial damage in myocarditis by restoring the microbiota composition.}, journal = {Pharmacological research}, volume = {139}, number = {}, pages = {412-421}, doi = {10.1016/j.phrs.2018.11.042}, pmid = {30508676}, issn = {1096-1186}, mesh = {Animals ; Dysbiosis/microbiology/pathology/*therapy ; *Fecal Microbiota Transplantation ; Male ; Mice, Inbred BALB C ; Microbiota ; Myocarditis/microbiology/pathology/*therapy ; Myocardium/pathology ; }, abstract = {Myocarditis can be caused by several infectious and noninfectious causes. Treatment for myocarditis is still a difficult task in clinical practice. The gut microbiota is related to cardiovascular diseases such as atherosclerosis and hypertension. However, little is known about the role of the gut microbiota in myocarditis. In our study, we tested the hypothesis that gut dysbiosis is associated with myocarditis. We focused on whether fecal microbiota transplantation (FMT) can be used as an effective treatment for myocarditis. We used an experimental autoimmune myocarditis (EAM) mouse model. Fecal samples were isolated from the control and EAM groups for bacterial genome analysis. We observed an increase in microbial richness and diversity in the myocarditis mice. These changes were accompanied by an increased Firmicutes/Bacteroidetes ratio. We also evaluated the efficacy of FMT for the treatment of myocarditis. EAM mouse guts were repopulated with fecal contents from an untreated male mouse donor. We found that myocardial injury was improved by diminished inflammatory infiltration, showing that IFN-γ gene expression in the heart tissue and CD4[+]IFN-γ[+] cells in the spleen were decreased after FMT in EAM mice. We also found that FMT was able to rebalance the gut microbiota by restoring the Bacteroidetes population and reshaping the microbiota composition. Myocarditis is associated with gut microbiota dysbiosis and characterized by an increased F/B ratio. FMT treatment can rebalance the gut microbiota and attenuate myocarditis. Thus, FMT may be a potential therapeutic strategy for the treatment of myocarditis.}, }
@article {pmid30506900, year = {2019}, author = {Leedahl, DD and Personett, HA and Nagpal, A and Barreto, EF}, title = {Prevention of Clostridium difficile Infection in Critically Ill Adults.}, journal = {Pharmacotherapy}, volume = {39}, number = {3}, pages = {399-407}, doi = {10.1002/phar.2200}, pmid = {30506900}, issn = {1875-9114}, mesh = {Adult ; Anti-Bacterial Agents/*administration &amp; dosage ; Antimicrobial Stewardship/methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*prevention &amp; control ; Critical Illness ; Fecal Microbiota Transplantation/methods ; Humans ; Probiotics/administration &amp; dosage ; Risk Factors ; }, abstract = {The incidence and severity of Clostridium difficile infection (CDI) remain high across intensive care units in the United States despite national efforts to decrease this escalating health care burden. Most published literature and guidelines address treatment rather than prevention, yet this approach may be too downstream to limit morbidity and mortality from the disease and its complications. Mechanisms to prevent CDI successfully include reducing modifiable risk factors and minimizing horizontal transmission of C. difficile spores between patients and the health care environment. Because CDI prevention is characterized by a bundled approach, it is difficult to quantify the individual impact of any one element; however, a number of patient- and facility-level strategies can be considered for CDI prevention. Robust hygiene strategies, diagnostic and antimicrobial stewardship, and particular prophylaxis maneuvers such as continuation of oral vancomycin or fidaxomicin in the setting of systemic antibiotics have all demonstrated benefit. The preventive roles of deprescribing acid suppressants, routine use of probiotics, or early fecal microbiota transplantation remain unclear. The focus of this review is to summarize the evidence related to primary and secondary CDI prevention in critically ill adults and provide a concise implementation pathway for clinicians and policymakers.}, }
@article {pmid30506577, year = {2019}, author = {Gong, S and Yan, Z and Liu, Z and Niu, M and Fang, H and Li, N and Huang, C and Li, L and Chen, G and Luo, H and Chen, X and Zhou, H and Hu, J and Yang, W and Huang, Q and Schnabl, B and Chang, P and Billiar, TR and Jiang, Y and Chen, P}, title = {Intestinal Microbiota Mediates the Susceptibility to Polymicrobial Sepsis-Induced Liver Injury by Granisetron Generation in Mice.}, journal = {Hepatology (Baltimore, Md.)}, volume = {69}, number = {4}, pages = {1751-1767}, doi = {10.1002/hep.30361}, pmid = {30506577}, issn = {1527-3350}, support = {2016A030306043//Natural Science Funds for Distinguished Young Scholar of Guangdong province/International ; 201804//the funding from State Key Laboratory of Organ Failure Research/International ; U1601225//NSFC-Guangdong Joint Foundation of China/International ; 201607020016//Key Scientific and Technological Program of Guangzhou City/International ; 81372030//National Natural Science Foundation of China/International ; N/A//the award of Young Pearl Scholars of Guangdong province/International ; 201804//funding from State Key Laboratory of Organ Failure Research/International ; N/A//THE award of Young Pearl Scholars of Guangdong province/International ; }, mesh = {Animals ; Coinfection/*complications ; Cytochrome P-450 CYP1A1/metabolism ; Cytokines/metabolism ; *Gastrointestinal Microbiome ; Granisetron/*metabolism ; Humans ; Liver Diseases/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; RAW 264.7 Cells ; Receptors, Serotonin, 5-HT3/genetics/metabolism ; Sepsis/*microbiology ; Toll-Like Receptor 4/metabolism ; }, abstract = {Sepsis-induced liver injury is recognized as a key problem in intensive care units. The gut microbiota has been touted as an important mediator of liver disease development; however, the precise roles of gut microbiota in regulating sepsis-induced liver injury are unknown. Here, we aimed to investigate the role of the gut microbiota in sepsis-induced liver injury and the underlying mechanism. Cecal ligation and puncture (CLP) was used to induce polymicrobial sepsis and related liver injury. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. Metabolomics analysis was performed to characterize the metabolic profile differences between sepsis-resistant (Res; survived to 7 days after CLP) and sepsis-sensitive (Sen; moribund before or approximately 24 hours after CLP) mice. Mice gavaged with feces from Sen mice displayed more-severe liver damage than did mice gavaged with feces from Res mice. The gut microbial metabolic profile between Sen and Res mice was different. In particular, the microbiota from Res mice generated more granisetron, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, than the microbiota from Sen mice. Granisetron protected mice against CLP-induced death and liver injury. Moreover, proinflammatory cytokine expression by macrophages after lipopolysaccharide (LPS) challenge was markedly reduced in the presence of granisetron. Both treatment with granisetron and genetic knockdown of the 5-HT3A receptor in cells suppressed nuclear factor kappa B (NF-кB) transactivation and phosphorylated p38 (p-p38) accumulation in macrophages. Gut microbial granisetron levels showed a significantly negative correlation with plasma alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels in septic patients. Conclusion: Our study indicated that gut microbiota plays a key role in the sensitization of sepsis-induced liver injury and associates granisetron as a hepatoprotective compound during sepsis development.}, }
@article {pmid30505519, year = {2018}, author = {Russell, L and Monaghan, T and Kao, D}, title = {The need to move away from fecal transplant towards targeted, refined microbiome therapy.}, journal = {Journal of thoracic disease}, volume = {10}, number = {10}, pages = {E755-E757}, pmid = {30505519}, issn = {2072-1439}, }
@article {pmid30502914, year = {2018}, author = {Niederwerder, MC}, title = {Fecal microbiota transplantation as a tool to treat and reduce susceptibility to disease in animals.}, journal = {Veterinary immunology and immunopathology}, volume = {206}, number = {}, pages = {65-72}, pmid = {30502914}, issn = {1873-2534}, mesh = {Animals ; *Disease Susceptibility ; *Fecal Microbiota Transplantation ; Veterinary Medicine ; }, abstract = {Fecal microbiota transplantation (FMT) is the process by which fecal microbiota are donated from a healthy individual and subsequently transplanted into a diseased or young individual. The mechanism by which FMT is effective is believed to be due to enhanced beneficial microbes, increased microbiome diversity, and restored normal flora. Beneficial gut microorganisms not only play a role in maintaining an intestinal barrier and metabolizing nutrients, but importantly, these microbes help regulate local and systemic immune function. Although FMT has been described for several centuries, only recently has it been utilized as a mainstream therapy in humans and significantly considered for applications in other species. In humans and animals, gastrointestinal diseases are by far the most widely accepted FMT-treatable conditions; however, recent research has shown exceptional promise for FMT being used to treat or prevent other conditions, including those outside of the gastrointestinal tract. Overall, FMT is likely an underutilized, widely-available, and inexpensive tool for improving the health and response to disease in animals. In this review, the effects of FMT on veterinary diseases and potential applications for FMT in animals are discussed.}, }
@article {pmid30502308, year = {2019}, author = {Davido, B and Batista, R and Fessi, H and Michelon, H and Escaut, L and Lawrence, C and Denis, M and Perronne, C and Salomon, J and Dinh, A}, title = {Fecal microbiota transplantation to eradicate vancomycin-resistant enterococci colonization in case of an outbreak.}, journal = {Medecine et maladies infectieuses}, volume = {49}, number = {3}, pages = {214-218}, doi = {10.1016/j.medmal.2018.11.002}, pmid = {30502308}, issn = {1769-6690}, mesh = {Aged ; Aged, 80 and over ; Antibiosis/physiology ; Clostridium Infections/epidemiology/prevention &amp; control ; Disease Eradication/*methods ; Disease Outbreaks ; Dysbiosis/epidemiology/microbiology/therapy ; *Fecal Microbiota Transplantation/statistics &amp; numerical data ; Female ; Follow-Up Studies ; France/epidemiology ; Gram-Positive Bacterial Infections/*epidemiology/microbiology/prevention &amp; control/*therapy ; Humans ; Intestines/microbiology ; Male ; Middle Aged ; Pilot Projects ; Risk Factors ; Vancomycin/therapeutic use ; *Vancomycin-Resistant Enterococci/isolation &amp; purification/physiology ; }, abstract = {OBJECTIVE: A rapid and worrying emergence of vancomycin-resistant enterococci (VRE) gut colonization is occurring worldwide and may be responsible for outbreaks, especially in healthcare facilities. While no efficient decolonization strategies are recommended, we assessed fecal microbiota transplantation (FMT) to eradicate VRE colonization.<br><br>PATIENTS AND METHOD: Our main objective was to measure the impact of FMT on decolonization of VRE carriers, confirmed by at least two consecutive negative rectal swabs at one-week interval during a 3-month follow-up period. Patients received no antibiotic prior to the FMT.<br><br>RESULTS: After a month only three patients remained colonized with VRE. Decolonization was associated with 87.5% (n=7) of success after three months as only one patient remained colonized.<br><br>CONCLUSION: Our first results confirm that the FMT seems to be safe, with an impact on VRE colonization over time that may help control outbreaks.}, }
@article {pmid30513674, year = {2018}, author = {Carrera-Quintanar, L and Ortuño-Sahagún, D and Franco-Arroyo, NN and Viveros-Paredes, JM and Zepeda-Morales, AS and Lopez-Roa, RI}, title = {The Human Microbiota and Obesity: A Literature Systematic Review of In Vivo Models and Technical Approaches.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, pmid = {30513674}, issn = {1422-0067}, support = {CB-2015-256736//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; CB-2017-A1-S-51026//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; 620112//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; UDG-PTC-1313//SEP PRODEP/ ; }, mesh = {Animals ; Gastrointestinal Microbiome/physiology ; Humans ; Inflammation/immunology/microbiology ; Microbiota/*physiology ; Obesity/immunology/*microbiology ; }, abstract = {Obesity is a noncommunicable disease that affects a considerable part of humanity. Recently, it has been recognized that gut microbiota constitutes a fundamental factor in the triggering and development of a large number of pathologies, among which obesity is one of the most related to the processes of dysbiosis. In this review, different animal model approaches, methodologies, and genome scale metabolic databases were revisited to study the gut microbiota and its relationship with metabolic disease. As a data source, PubMed for English-language published material from 1 January 2013, to 22 August 2018, were screened. Some previous studies were included if they were considered classics or highly relevant. Studies that included innovative technical approaches or different in vivo or in vitro models for the study of the relationship between gut microbiota and obesity were selected after a 16-different-keyword exhaustive search. A clear panorama of the current available options for the study of microbiota's influence on obesity, both for animal model election and technical approaches, is presented to the researcher. All the knowledge generated from the study of the microbiota opens the possibility of considering fecal transplantation as a relevant therapeutic alternative for obesity and other metabolic disease treatment.}, }
@article {pmid30510995, year = {2019}, author = {Kiyohara, H and Sujino, T and Teratani, T and Miyamoto, K and Arai, MM and Nomura, E and Harada, Y and Aoki, R and Koda, Y and Mikami, Y and Mizuno, S and Naganuma, M and Hisamatsu, T and Kanai, T}, title = {Toll-Like Receptor 7 Agonist-Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {7}, number = {1}, pages = {135-156}, pmid = {30510995}, issn = {2352-345X}, mesh = {Animals ; B-Lymphocytes/immunology ; Cell Movement ; Colitis/chemically induced/*immunology/*microbiology/pathology ; Dermatitis/*complications/immunology ; Dextran Sulfate ; Disease Progression ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Hematopoietic Stem Cells/metabolism ; Imiquimod/adverse effects ; Immunoglobulin D/metabolism ; Immunoglobulin M/metabolism ; Intestines/immunology/pathology ; Lactobacillus/physiology ; Lymph Nodes/pathology ; Lymphocyte Depletion ; Mice, Inbred C57BL ; Permeability ; Psoriasis/complications/immunology ; Toll-Like Receptor 7/*agonists ; }, abstract = {BACKGROUND &amp; AIMS: Psoriasis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases occurring in the skin and gut, respectively. It is well established that psoriasis and IBD have high concordance rates, and similar changes in immune cells and microbiome composition have been reported in both conditions. To study this connection, we used a combination murine model of psoriatic dermatitis and colitis in which mice were treated topically with the Toll-like receptor 7 agonist imiquimod (IMQ) and fed dextran sulfate sodium (DSS).<br><br>METHODS: We applied IMQ topically to B6 mice (IMQ mice) and subsequently fed them 2% DSS in their drinking water. Disease activity and immune cell phenotypes were analyzed, and the microbial composition of fecal samples was investigated using 16S ribosomal RNA sequencing. We transplanted feces from IMQ mice to germ-free IQI/Jic (IQI) mice and fed them DSS to assess the effect of the gut microbiome on disease.<br><br>RESULTS: We first confirmed that IMQ mice showed accelerated DSS colitis. IMQ mice had decreased numbers of IgD[+] and IgM[+] B cells and increased numbers of non-cytokine-producing macrophages in the gut. Moreover, the gut microbiomes of IMQ mice were perturbed, with significant reductions of Lactobacillus johnsonii and Lactobacillus reuteri populations. Germ-free mice transplanted with feces from IMQ mice, but not with feces from untreated mice, also developed exacerbated DSS colitis.<br><br>CONCLUSIONS: These results suggest that skin inflammation may contribute to pathogenic conditions in the gut via immunologic and microbiological changes. Our finding of a novel potential skin-gut interaction provides new insights into the coincidence of psoriasis and IBD.}, }
@article {pmid30510291, year = {2019}, author = {Thomas, H}, title = {FMT for drug-induced colitis.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {16}, number = {1}, pages = {4}, doi = {10.1038/s41575-018-0092-8}, pmid = {30510291}, issn = {1759-5053}, mesh = {*Colitis ; *Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid30500860, year = {2018}, author = {Leon-Coria, A and Kumar, M and Moreau, F and Chadee, K}, title = {Defining cooperative roles for colonic microbiota and Muc2 mucin in mediating innate host defense against Entamoeba histolytica.}, journal = {PLoS pathogens}, volume = {14}, number = {11}, pages = {e1007466}, pmid = {30500860}, issn = {1553-7374}, support = {MOP-142776//Canadian Institutes of Health Research/International ; }, mesh = {Animals ; Cell Line ; Colon/metabolism/pathology ; Entamoeba histolytica/immunology/*metabolism/pathogenicity ; Epithelial Cells/metabolism ; Gastrointestinal Microbiome/*immunology ; Gene Expression Regulation ; Goblet Cells/metabolism ; Humans ; Immunity, Innate/immunology ; Inflammation/pathology ; Intestinal Mucosa/immunology ; Mice ; Mice, Inbred C57BL ; Microbiota ; Mucin-1 ; Mucin-2/*immunology ; Mucins/metabolism ; }, abstract = {Amebiasis is caused by the protozoan parasite Entamoeba histolytica (Eh), a potentially fatal disease occurring mainly in developing countries. How Eh interacts with innate host factors in the gut is poorly understood. Eh resides and feed in/on the outer colonic mucus layer and thus share an ecological niche with indigenous microbiota. As gut microbiota regulates innate immune responses, in this study we characterized the cooperative roles that microbiota and the mucus layer play in Eh-induced pro-inflammatory responses in the colon. To study this, we used antibiotics treated and non-treated specific pathogen free Muc2-/- and Muc2+/+ littermates and germ-free mice inoculated with Eh in colonic loops as a short infection model. In antibiotic treated Muc2-/- and Muc2+/+ littermates, Eh elicited robust mucus and water secretions, enhanced pro-inflammatory cytokines and chemokine expression with elevated MPO activity and higher pathology scores as compared to the modest response observed in non-antibiotic treated littermates. Host responses were microbiota specific as mucus secretion and pro-inflammatory responses were attenuated following homologous fecal microbial transplants in antibiotic-treated Muc2+/+ quantified by secretion of 3H-glucosamine newly synthesized mucin, Muc2 mucin immunostaining and immunohistochemistry. Eh-elicited pro-inflammatory responses and suppressed goblet cell transcription factor Math1 as revealed by in vivo imaging of Eh-colonic loops in Math1GFP mice, and in vitro using Eh-stimulated LS174T human colonic goblet cells. Eh in colonic loops increased bacterial translocation of bioluminescent E. coli and indigenous bacteria quantified by FISH and quantitative PCR. In germ-free animals, Eh-induced mucus/water secretory responses, but acute pro-inflammatory responses and MPO activity were severely impaired, allowing the parasite to bind to and disrupt mucosal epithelial cells. These findings have identified key roles for intestinal microbiota and mucus in regulating innate host defenses against Eh, and implicate dysbiosis as a risk factor for amebiasis that leads to exacerbated immune responses to cause life-threatening disease.}, }
@article {pmid30498879, year = {2019}, author = {Mathias, F and Curti, C and Montana, M and Bornet, C and Vanelle, P}, title = {Management of adult Clostridium difficile digestive contaminations: a literature review.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {38}, number = {2}, pages = {209-231}, pmid = {30498879}, issn = {1435-4373}, mesh = {Adult ; Anti-Bacterial Agents/standards/*therapeutic use ; Clostridioides difficile/drug effects/*isolation &amp; purification ; Clostridium Infections/complications/microbiology/*therapy ; Disease Management ; Drug Resistance, Bacterial ; Fecal Microbiota Transplantation ; Gastroenteritis/complications/*microbiology/therapy ; Humans ; Recurrence ; }, abstract = {Clostridium difficile infections (CDI) dramatically increased during the last decade and cause a major public health problem. Current treatments are limited by the high disease recurrence rate, severity of clinical forms, disruption of the gut microbiota, and colonization by vancomycin-resistant enterococci (VRE). In this review, we resumed current treatment options from official recommendation to promising alternatives available in the management of adult CDI, with regard to severity and recurring or non-recurring character of the infection. Vancomycin remains the first-line antibiotic in the management of mild to severe CDI. The use of metronidazole is discussed following the latest US recommendations that replaced it by fidaxomicin as first-line treatment of an initial episode of non-severe CDI. Fidaxomicin, the most recent antibiotic approved for CDI in adults, has several advantages compared to vancomycin and metronidazole, but its efficacy seems limited in cases of multiple recurrences. Innovative therapies such as fecal microbiota transplantation (FMT) and antitoxin antibodies were developed to limit the occurrence of recurrence of CDI. Research is therefore very active, and new antibiotics are being studied as surotomycin, cadazolid, and rinidazole.}, }
@article {pmid30489686, year = {2019}, author = {Takahashi, M and Ishikawa, D and Sasaki, T and Lu, YJ and Kuwahara-Arai, K and Kamei, M and Shibuya, T and Osada, T and Hiramatsu, K and Nagahara, A}, title = {Faecal freezing preservation period influences colonization ability for faecal microbiota transplantation.}, journal = {Journal of applied microbiology}, volume = {126}, number = {3}, pages = {973-984}, doi = {10.1111/jam.14167}, pmid = {30489686}, issn = {1365-2672}, support = {JP16K09328//JSPS KAKENHI/ ; S1201013//Japanese Ministry of Education, Culture, Sports, Science and Technology/ ; }, mesh = {*Cryopreservation ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; *Microbial Viability ; }, abstract = {AIMS: There has been growing interest in faecal microbiota transplantation (FMT) as treatment. Although, frozen donor faeces preserved at -20°C has been widely used for practical advantages, freezing at -20°C can affect bacterial viability. Adequacy evaluation of fresh and frozen faeces as the transplant is necessary for the methodological improvement of FMT.<br><br>METHODS AND RESULTS: The viable bacterial compositions of faecal specimens under fresh and freezing conditions were compared by a microbiome analysis using propidium monoazide (PMA microbiome). In addition, recovery abilities from bacterial reduction by antibiotics were compared between fresh and frozen FMT using a murine model. PMA microbiome results suggested that freezing and freeze-thawing did not significantly affect in&#xa0;vitro faecal bacterial viability. However, the recovery effect from antimicrobial cleansing in frozen FMT was reduced in a freezing time-dependent manner, especially prominent in Actinobacteria and Bacteroidetes phyla.<br><br>CONCLUSIONS: Short-term freezing preservation of faeces exhibited maintenance of enteric colonization ability in frozen FMT in comparison to 1&#xa0;month -20&#xb0;C-preservation.<br><br>Long-term -20&#xb0;C-preservation of transplanted faeces can result in instability of the clinical outcome in FMT therapy. The standardization of practical procedures of FMT therapy according to disease types is desirable.}, }
@article {pmid30486642, year = {2019}, author = {Mosso, E and Boano, V and Grassini, M and Battaglia, E and Pellicano, R}, title = {Microscopic colitis: a narrative review with clinical approach.}, journal = {Minerva gastroenterologica e dietologica}, volume = {65}, number = {1}, pages = {53-62}, doi = {10.23736/S1121-421X.18.02539-4}, pmid = {30486642}, issn = {1827-1642}, mesh = {Anti-Inflammatory Agents/therapeutic use ; Budesonide/therapeutic use ; Colitis, Microscopic/*diagnosis/epidemiology/*therapy ; Colonoscopy ; Comorbidity ; Diarrhea/etiology ; Fecal Microbiota Transplantation ; Humans ; Immunologic Factors/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {Microscopic colitis (MC) is diagnosed in presence of microscopic alterations of colonic mucosa, in patients without macroscopic lesions who referred for chronic diarrhea. The two types of MC are lymphocytic colitis (LC) and collagenous colitis (CC), but it is unclear whether these are the different expression of one unique disease or if they are distinct conditions. Today, although MC represents a consistent health problem, being responsible for a large part of gastroenterological consultations for diarrhea, it remains often underestimated. The detailed pathogenesis of MC has not been determined yet. Probably, it is the result of an interaction between individual, environmental and genetic factors. The most relevant risk factor for the development of MC is the use of certain drugs (such as non-steroidal anti-inflammatory drugs [NSAIDs], proton pump inhibitors [PPIs], selective serotonin reuptake inhibitors, beta-blockers, statins). Smoking is another relevant factor reported as associated with the development of MC. Diagnosis needs the execution of a colonoscopy in patients complaining about chronic diarrhea and abdominal pain. The crucial role is played by histology: MC is characterized by the presence of colonic mucosal lymphocytic infiltrate, with intraepithelial lymphocytes ≥20 per 100 enteric surface cells, in CC there is a typical subepithelial collagen layer, whose thickness is ≥10 μm. We carried out a review of the current literature to rule out what is new on epidemiology, diagnosis and therapy of MC.}, }
@article {pmid30486338, year = {2018}, author = {Amedei, A and Boem, F}, title = {I've Gut A Feeling: Microbiota Impacting the Conceptual and Experimental Perspectives of Personalized Medicine.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, pmid = {30486338}, issn = {1422-0067}, support = {FAS SALUTE 2014//Regione Toscana/ ; P2016.0808//Ente Cassa di Risparmio di Firenze/ ; }, mesh = {Animals ; Biodiversity ; Biological Therapy ; Disease Susceptibility ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Genomics/methods ; Humans ; Metagenomics/methods ; Microbiota ; Organ Specificity ; *Precision Medicine/methods ; Research ; Symbiosis ; }, abstract = {In recent years, the human microbiota has gained increasing relevance both in research and clinical fields. Increasing studies seem to suggest the centrality of the microbiota and its composition both in the development and maintenance of what we call "health" and in generating and/or favoring (those cases in which the microbiota's complex relational architecture is dysregulated) the onset of pathological conditions. The complex relationships between the microbiota and human beings, which invest core notions of biomedicine such as "health" and "individual," do concern not only problems of an empirical nature but seem to require the need to adopt new concepts and new perspectives in order to be properly analysed and utilized, especially for their therapeutic implementation. In this contribution we report and discuss some of the theoretical proposals and innovations (from the ecological component to the notion of polygenomic organism) aimed at producing this change of perspective. In conclusion, we summarily analyze what impact and what new challenges these new approaches might have on personalized/person centred/precision medicine.}, }
@article {pmid30483574, year = {2018}, author = {Shi, YC and Yang, YS}, title = {Fecal microbiota transplantation: Current status and challenges in China.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {2}, number = {4}, pages = {114-116}, pmid = {30483574}, issn = {2397-9070}, }
@article {pmid30480772, year = {2018}, author = {Imdad, A and Nicholson, MR and Tanner-Smith, EE and Zackular, JP and Gomez-Duarte, OG and Beaulieu, DB and Acra, S}, title = {Fecal transplantation for treatment of inflammatory bowel disease.}, journal = {The Cochrane database of systematic reviews}, volume = {11}, number = {11}, pages = {CD012774}, pmid = {30480772}, issn = {1469-493X}, support = {KL2 TR002245/TR/NCATS NIH HHS/United States ; TL1 TR002244/TR/NCATS NIH HHS/United States ; }, mesh = {Colitis, Ulcerative/*therapy ; Crohn Disease/*therapy ; Dysbiosis/complications/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Randomized Controlled Trials as Topic ; Recurrence ; Remission Induction ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal tract that is thought to be associated with a complex interplay between microbes and the immune system, leading to an abnormal inflammatory response in genetically susceptible individuals. Dysbiosis, characterized by the alteration of the composition of the resident commensal bacteria in a host compared to healthy individuals, is thought to play a major role in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD), two subtypes of IBD. There is growing interest to correct the underlying dysbiosis through the use of fecal microbiota transplantation (FMT) for the treatment of IBD.<br><br>OBJECTIVES: The objective of this systematic review was to assess the efficacy and safety of FMT for the treatment of IBD.<br><br>SEARCH METHODS: We searched the MEDLINE, Embase, Cochrane Library, and Cochrane IBD Group Specialized Register databases from inception to 19 March 2018. We also searched ClinicalTrials.gov, ISRCTN metaRegister of Controlled Trials, and the Conference Proceedings Citation Index.<br><br>SELECTION CRITERIA: Only randomized trials or non-randomized studies with a control arm were considered for inclusion. Adults or pediatric participants with UC or CD were eligible for inclusion. Eligible interventions were FMT defined as the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a someone with UC or CD. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, or no intervention.<br><br>DATA COLLECTION AND ANALYSIS: Two authors independently screened the titles and extracted data from the included studies. We used the Cochrane risk of bias tool to assess study bias. The primary outcomes were induction of clinical remission, clinical relapse, and serious adverse events. Secondary outcomes included clinical response, endoscopic remission and endoscopic response, quality of life scores, laboratory measures of inflammation, withdrawals, and microbiome outcomes. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference and 95% CI for continuous outcomes. Random-effects meta-analysis models were used to synthesize effect sizes across trials. The overall certainty of the evidence supporting the primary and selected secondary outcomes was rated using the GRADE criteria.<br><br>MAIN RESULTS: Four studies with a total of 277 participants were included. These studies assessed the efficacy of FMT for treatment of UC in adults; no eligible trials were found for the treatment of CD. Most participants had mild to moderate UC. Two studies were conducted in Australia, one study was conducted in Canada, and another in the Netherlands. Three of the included studies administered FMT via the rectal route and one study administered FMT via the nasoduodenal route. Three studies were rated as low risk of bias. One study (abstract publication) was rated as unclear risk of bias. Combined results from four studies (277 participants) suggest that FMT increases rates of clinical remission by two-fold in patients with UC compared to controls. At 8 weeks, 37% (52/140) of FMT participants achieved remission compared to 18% (24/137) of control participants (RR 2.03, 95 % CI, 1.07 to 3.86; I&#xb2; = 50%; low certainty evidence). One study reported data on relapse at 12 weeks among participants who achieved remission. None of the FMT participants (0/7) relapsed at 12 weeks compared to 20% of control participants (RR 0.28, 95% CI 0.02 to 4.98, 17 participants, very low certainty evidence). It is unclear whether there is a difference in serious adverse event rates between the intervention and control groups. Seven per cent (10/140) of FMT participants had a serious adverse event compared to 5% (7/137) of control participants (RR 1.40, 95% CI 0.55 to 3.58; 4 studies; I&#xb2; = 0%; low certainty evidence). Serious adverse events included worsening of UC necessitating intravenous steroids or surgery; infection such as Clostridium difficile and cytomegalovirus, small bowel perforation and pneumonia. Adverse events were reported by two studies and the pooled data did not show any difference between the study groups. Seventy-eight per cent (50/64) of FMT participants had an adverse event compared to 75% (49/65) of control participants (RR 1.03, 95% CI 0.81 to 1.31; I&#xb2; = 31%; moderate certainty evidence). Common adverse events included abdominal pain, nausea, flatulence, bloating, upper respiratory tract infection, headaches, dizziness, and fever. Four studies reported on clinical response at 8 weeks. Forty-nine per cent (68/140) of FMT participants had a clinical response compared to 28% (38/137) of control participants (RR 1.70, 95% CI 0.98 to 2.95, I&#xb2; = 50%, low certainty evidence). Endoscopic remission at 8 weeks was reported by three studies and the combined results favored FMT over the control group. Thirty per cent (35/117) of FMT participants achieved endoscopic remission compared to 10% (11/112) of control participants (RR 2.96, 95 % CI 1.60 to 5.48, I&#xb2; = 0%; low certainty evidence).<br><br>AUTHORS' CONCLUSIONS: Fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time. Additional high-quality studies are needed to further define the optimal parameters of FMT in terms of route, frequency, volume, preparation, type of donor and the type and disease severity. No studies assessed efficacy of FMT for induction of remission in CD or in pediatric participants. In addition, no studies assessed long-term maintenance of remission in UC or CD. Future studies are needed to address the therapeutic benefit of FMT in CD and the long-term FMT-mediated maintenance of remission in UC or CD.}, }
@article {pmid30479468, year = {2018}, author = {Panes, J and Reinisch, W and Rupniewska, E and Khan, S and Forns, J and Khalid, JM and Bojic, D and Patel, H}, title = {Burden and outcomes for complex perianal fistulas in Crohn's disease: Systematic review.}, journal = {World journal of gastroenterology}, volume = {24}, number = {42}, pages = {4821-4834}, pmid = {30479468}, issn = {2219-2840}, mesh = {Adipose Tissue/cytology ; Combined Modality Therapy/methods ; *Cost of Illness ; Crohn Disease/*complications ; Cutaneous Fistula/*epidemiology/etiology/therapy ; Drainage/methods ; Humans ; Immunosuppressive Agents/therapeutic use ; *Quality of Life ; Rectal Fistula/*epidemiology/etiology/therapy ; Recurrence ; Stem Cell Transplantation ; Stem Cells ; Treatment Failure ; Tumor Necrosis Factor-alpha/antagonists &amp; inhibitors ; }, abstract = {AIM: To systematically review the literature on epidemiology, disease burden, and treatment outcomes for Crohn's disease (CD) patients with complex perianal fistulas.<br><br>METHODS: PubMed, Embase, and Cochrane were searched for relevant articles (published 2000-November 2016) and congress abstracts (published 2011-November 2016).<br><br>RESULTS: Of 535 records reviewed, 62 relevant sources were identified (mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14% (follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment (failure and relapse rates, respectively: medical, 12%-73% and 0%-41%; surgical: 0%-100% and 11%-20%; combined medical/surgical: 0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies (1 of infliximab; 3 of surgical interventions) have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-&#x3b1; dose escalation in patients with complex perianal fistulas in CD.<br><br>CONCLUSION: Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to anti-tumour necrosis factor-&#x3b1; agents, as evidenced by high failure and relapse rates.}, }
@article {pmid30479380, year = {2019}, author = {Wang, Y and Wiesnoski, DH and Helmink, BA and Gopalakrishnan, V and Choi, K and DuPont, HL and Jiang, ZD and Abu-Sbeih, H and Sanchez, CA and Chang, CC and Parra, ER and Francisco-Cruz, A and Raju, GS and Stroehlein, JR and Campbell, MT and Gao, J and Subudhi, SK and Maru, DM and Blando, JM and Lazar, AJ and Allison, JP and Sharma, P and Tetzlaff, MT and Wargo, JA and Jenq, RR}, title = {Author Correction: Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.}, journal = {Nature medicine}, volume = {25}, number = {1}, pages = {188}, doi = {10.1038/s41591-018-0305-2}, pmid = {30479380}, issn = {1546-170X}, abstract = {In the version of this article originally published, an author was missing from the author list. Alexander J. Lazar should have been included between Jorge M. Blando and James P. Allison. The author has been added to the list, and the author contributions section has been updated to include Alexander J. Lazar's contribution to the study. The error has been corrected in the print, PDF and HTML versions of the manuscript.}, }
@article {pmid30478426, year = {2019}, author = {Sidaway, P}, title = {Faecal transplantation reverses colitis.}, journal = {Nature reviews. Clinical oncology}, volume = {16}, number = {2}, pages = {66}, doi = {10.1038/s41571-018-0139-3}, pmid = {30478426}, issn = {1759-4782}, }
@article {pmid30474827, year = {2018}, author = {Mehta, R and Kabrawala, M and Nandwani, S and Kalra, P and Patel, C and Desai, P and Parekh, K}, title = {Preliminary experience with single fecal microbiota transplant for treatment of recurrent overt hepatic encephalopathy-A case series.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {37}, number = {6}, pages = {559-562}, pmid = {30474827}, issn = {0975-0711}, mesh = {Adult ; Aged ; Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Hepatic Encephalopathy/*therapy ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {Experimental studies demonstrated that fecal microbiota transplant (FMT) may reverse intestinal microbial dysbiosis. In this retrospective case series, we share our experience of treating recurrent overt hepatic encephalopathy (HE) with single FMT treatment. A total of 10 patients, age ranged from 25 to 65 years, were treated with single FMT through colonoscopy using fecal material received from rigorously screened patient-identified donors. There was sustained clinical response with single FMT treatment in 6 patients at post-treatment week 20. Arterial ammonia concentration decreased considerably (96 [87.25-117.75] vs. 74 [70-82]; p = 0.024) at post-treatment week 20. Moreover, there was statistically significant decrease in Child-Turcotte-Pugh (CTP) score (9.5 [9-10.75] vs. 8 [7-8]; p = 0.005) and model for end-stage liver disease (MELD) score (18 [16.25-19] vs. 15 [14-16]; p = 0.008). Four patients experienced six adverse-events. Overt HE and re-hospitalization were observed in 3 and 2 patients, respectively. One patient (who also experienced overt HE) died within 2 months of the index procedure.}, }
@article {pmid30474116, year = {2019}, author = {Dai, Z and Zhang, J and Wu, Q and Chen, J and Liu, J and Wang, L and Chen, C and Xu, J and Zhang, H and Shi, C and Li, Z and Fang, H and Lin, C and Tang, D and Wang, D}, title = {The role of microbiota in the development of colorectal cancer.}, journal = {International journal of cancer}, volume = {145}, number = {8}, pages = {2032-2041}, pmid = {30474116}, issn = {1097-0215}, mesh = {Carcinogenesis/genetics ; Colorectal Neoplasms/genetics/*microbiology/therapy ; Epigenesis, Genetic ; Fecal Microbiota Transplantation/methods/trends ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology/pathology ; Microbiota/*physiology ; }, abstract = {Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation.}, }
@article {pmid30472293, year = {2019}, author = {Saïdani, N and Lagier, JC and Cassir, N and Million, M and Baron, S and Dubourg, G and Eldin, C and Kerbaj, J and Valles, C and Raoult, D and Brouqui, P}, title = {Faecal microbiota transplantation shortens the colonisation period and allows re-entry of patients carrying carbapenamase-producing bacteria into medical care facilities.}, journal = {International journal of antimicrobial agents}, volume = {53}, number = {4}, pages = {355-361}, doi = {10.1016/j.ijantimicag.2018.11.014}, pmid = {30472293}, issn = {1872-7913}, mesh = {Acinetobacter/*growth &amp; development ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Carbapenem-Resistant Enterobacteriaceae/*growth &amp; development ; Case-Control Studies ; Drug Resistance, Multiple, Bacterial/physiology ; Enterobacteriaceae Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Colonisation with carbapenemase-producing Enterobacteriaceae or Acinetobacter (CPE/A) is associated with complex medical care requiring implementation of specific isolation policies and limitation of patient discharge to other medical facilities. Faecal microbiota transplantation (FMT) has been proposed in order to reduce the duration of gut colonisation.<br><br>OBJECTIVES: This study investigated whether a dedicated protocol of FMT could reduce the negativation time of CPE/A intestinal carriage in patients whose medical care has been delayed due to such colonisation.<br><br>METHOD: A matched case-control retrospective study between patients who received FMT treatment and those who did not among CPE/A-colonised patients addressed for initial clustering at the current institute. The study adjusted two controls per case based on sex, age, bacterial species, and carbapenemase type. The primary outcome was delay in negativation of rectal-swab cultures.<br><br>RESULTS: At day 14 post FMT, 8/10 (80%) treated patients were cleared for intestinal CPE/A carriage. In the control group, 2/20 (10%) had spontaneous clearance at day 14 after CPE/A diagnosis. Faecal microbiota transplantation led patients to reduce the delay in decolonisation (median 3 days post FMT for treated patients vs. 50.5 days after the first documentation of digestive carriage for control patients) and discharge from hospital (median 19.5 days post FMT for treated patients vs. 41 for control patients).<br><br>CONCLUSION: Faecal microbiota transplantation is a safe and time-saving procedure to discharge CPE/A-colonised patients from the hospital. A standardised protocol, including 5 days of antibiotic treatment, bowel cleansing and systematic indwelling devices removal, should improve protocol effectiveness.}, }
@article {pmid30470860, year = {2019}, author = {Tillmann, S and Abildgaard, A and Winther, G and Wegener, G}, title = {Altered fecal microbiota composition in the Flinders sensitive line rat model of depression.}, journal = {Psychopharmacology}, volume = {236}, number = {5}, pages = {1445-1457}, pmid = {30470860}, issn = {1432-2072}, mesh = {Animals ; Depression/genetics/*microbiology/*psychology ; *Disease Models, Animal ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Male ; RNA, Ribosomal, 16S/genetics ; Rats ; Rats, Transgenic ; Swimming/physiology/psychology ; }, abstract = {RATIONALE: The gut microbiota is increasingly recognized as a potential mediator of psychiatric diseases. Depressed patients have been shown to have a different microbiota composition compared with healthy controls, and several lines of research now aim to restore this dysbiosis. To develop novel treatments, preclinical models may provide novel mechanistic insights.<br><br>OBJECTIVE AND METHODS: We characterized the gut microbiota of male adult Flinders sensitive line (FSL) rats, an animal model of depression, and their controls, Flinders resistant line (FRL) rats using 16S rRNA amplicon sequencing. Moreover, we performed fecal microbiota transplantation (using saline or pooled FRL/FSL feces) to study if the potential strain-specific differences could be transferred from one strain to the other, and if these differences were reflected in their depressive-like behavior in the forced swim test.<br><br>RESULTS: FSL rats tended to have lower bacterial richness and altered relative abundances of several bacterial phyla, families, and species, including higher Proteobacteria and lower Elusimicrobia and Saccharibacteria. There was a clear separation between FRL and FSL rat strains, but no effect of treatment, i.e., the bacterial composition of FSL rats receiving FRL feces was still more similar to FSL and not FRL rats. Similarly, the transplantation did not reverse behavioral differences in the forced swim test, although FSL feces significantly increased immobility compared with saline.<br><br>CONCLUSIONS: Our study showed that the gut microbiota composition of the depressive-like rats markedly differed from their controls, which may be of value for future microbiota-targeted work in this and similar animal models.}, }
@article {pmid30470496, year = {2018}, author = {Liu, J and Wu, M and He, J and Xiao, C and Xue, Y and Fu, T and Lin, C and Dong, D and Li, Z}, title = {Antibiotic-Induced Dysbiosis of Gut Microbiota Impairs Corneal Nerve Regeneration by Affecting CCR2-Negative Macrophage Distribution.}, journal = {The American journal of pathology}, volume = {188}, number = {12}, pages = {2786-2799}, pmid = {30470496}, issn = {1525-2191}, support = {R01 EY018239/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Cells, Cultured ; Corneal Injuries/*etiology/metabolism/pathology ; Disease Models, Animal ; Dysbiosis/chemically induced/*complications/metabolism ; Female ; Gastrointestinal Microbiome/*drug effects ; Macrophages/drug effects/*immunology/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Nerve Regeneration/drug effects/*immunology ; Receptors, CCR2/*physiology ; Wound Healing ; }, abstract = {Although antibiotics are useful, they can also bring negative effects. We found that antibiotic-treated mice exhibit an alteration in the gene expression profile of corneal tissues and a decrease in corneal nerve density. During corneal wound healing, antibiotic treatment was found to impair corneal nerve regeneration, an effect that could be largely reversed by reconstitution of the gut microbiota via fecal transplant. Furthermore, CCR2[-] corneal macrophages were found to participate in the repair of damaged corneal nerves, and a decrease in CCR2[-] corneal macrophages in antibiotic-treated mice, which could be reversed by fecal transplant, was observed. Adoptive transfer of CCR2[-] corneal macrophages promoted corneal nerve regeneration in antibiotic-treated mice. The application of probiotics after administration of antibiotics also restored the proportion of CCR2[-] corneal macrophages and increased the regeneration of corneal nerve fibers after epithelial abrasion. These results suggest that dysbiosis of the gut microbiota induced by antibiotic treatment impairs corneal nerve regeneration by affecting CCR2[-] macrophage distribution in the cornea. This study also indicates the potential of probiotics as a therapeutic strategy for promoting the regeneration of damaged corneal nerve fibers when the gut microbiota is in dysbiosis.}, }
@article {pmid30467295, year = {2018}, author = {Ganesan, K and Chung, SK and Vanamala, J and Xu, B}, title = {Causal Relationship between Diet-Induced Gut Microbiota Changes and Diabetes: A Novel Strategy to Transplant Faecalibacterium prausnitzii in Preventing Diabetes.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, pmid = {30467295}, issn = {1422-0067}, support = {R201714//Beijing Normal University-Hong Kong Baptist University United International College/ ; }, mesh = {Butyrates/metabolism ; Diabetes Mellitus/immunology/*microbiology/pathology/prevention &amp; control ; Diet/methods ; Dietary Fiber/administration &amp; dosage ; Dysbiosis/immunology/*microbiology/pathology/therapy ; Faecalibacterium prausnitzii/*physiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Probiotics/*therapeutic use ; Symbiosis/*physiology ; }, abstract = {The incidence of metabolic disorders, including diabetes, has elevated exponentially during the last decades and enhanced the risk of a variety of complications, such as diabetes and cardiovascular diseases. In the present review, we have highlighted the new insights on the complex relationships between diet-induced modulation of gut microbiota and metabolic disorders, including diabetes. Literature from various library databases and electronic searches (ScienceDirect, PubMed, and Google Scholar) were randomly collected. There exists a complex relationship between diet and gut microbiota, which alters the energy balance, health impacts, and autoimmunity, further causes inflammation and metabolic dysfunction, including diabetes. Faecalibacterium prausnitzii is a butyrate-producing bacterium, which plays a vital role in diabetes. Transplantation of F. prausnitzii has been used as an intervention strategy to treat dysbiosis of the gut's microbial community that is linked to the inflammation, which precedes autoimmune disease and diabetes. The review focuses on literature that highlights the benefits of the microbiota especially, the abundant of F. prausnitzii in protecting the gut microbiota pattern and its therapeutic potential against inflammation and diabetes.}, }
@article {pmid30464743, year = {2018}, author = {Langgartner, D and Vaihinger, CA and Haffner-Luntzer, M and Kunze, JF and Weiss, AJ and Foertsch, S and Bergdolt, S and Ignatius, A and Reber, SO}, title = {The Role of the Intestinal Microbiome in Chronic Psychosocial Stress-Induced Pathologies in Male Mice.}, journal = {Frontiers in behavioral neuroscience}, volume = {12}, number = {}, pages = {252}, pmid = {30464743}, issn = {1662-5153}, abstract = {Chronic psychosocial stress is a risk factor for the development of physical and mental disorders accompanied or driven by an activated immune system. Given that chronic stress-induced systemic immune activation is lacking in germ-free and antibiotics-treated mice, a causal role of the gut microbiome in the development of stress-related disorders is likely. To address this hypothesis in the current study we employed the chronic subordinate colony housing (CSC, 19 days) paradigm, a pre-clinically validated mouse model for chronic psychosocial stress, known to alter the gut microbial signature and to induce systemic low-grade inflammation, as well as physical and mental abnormalities. In detail, we investigated if (i) CSC-induced alterations can be prevented by repeated transplantation of feces (FT) from non-stressed single-housed control (SHC) mice during CSC exposure, and (ii) if the transplantation of a "stressed" CSC microbiome is able to induce CSC effects in SHC mice. Therefore, we repeatedly infused SHC and CSC recipient mice rectally with SHC donor feces at days 4 and 11 of the CSC paradigm and assessed anxiety-related behavior on day 19 as well as physiological, immunological, and bone parameters on day 20. Furthermore, SHC and CSC recipient mice were infused with CSC donor feces at respective days. To exclude effects of rectal infusions per se, another set of SHC and CSC mice was infused with saline, respectively. Our results showed that transplantation of SHC feces had mild stress-protective effects, indicated by an amelioration of CSC-induced thymus atrophy, anxiety, systemic low-grade inflammation, and alterations in bone homeostasis. Moreover, transplantation of CSC feces slightly aggravated CSC-induced systemic low-grade inflammation and alterations in bone homeostasis in SHC and/or CSC animals. In conclusion, our data provide evidence for a role of the host's microbiome in many, but not all, adverse consequences of chronic psychosocial stress. Moreover, our data are consistent with the hypothesis that transplantation of healthy feces might be a useful tool to prevent/treat different adverse outcomes of chronic stress. Finally, our data suggests that stress effects can be transferred to a certain extend via FT, proposing therapeutic approaches using FT to carefully screen fecal donors for their stress/trauma history.}, }
@article {pmid30463925, year = {2018}, author = {Bulow, C and Langdon, A and Hink, T and Wallace, M and Reske, KA and Patel, S and Sun, X and Seiler, S and Jones, S and Kwon, JH and Burnham, CA and Dantas, G and Dubberke, ER}, title = {Impact of Amoxicillin-Clavulanate followed by Autologous Fecal Microbiota Transplantation on Fecal Microbiome Structure and Metabolic Potential.}, journal = {mSphere}, volume = {3}, number = {6}, pages = {}, pmid = {30463925}, issn = {2379-5042}, support = {TL1 TR002344/TR/NCATS NIH HHS/United States ; U54 CK000609/CK/NCEZID CDC HHS/United States ; T32 HG000045/HG/NHGRI NIH HHS/United States ; KL2 TR002346/TR/NCATS NIH HHS/United States ; TL1 TR000449/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Amoxicillin-Potassium Clavulanate Combination/*administration &amp; dosage ; Anti-Bacterial Agents/*administration &amp; dosage ; Enema ; Fecal Microbiota Transplantation/*methods ; Female ; *Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Male ; *Metabolism ; *Microbiota ; Middle Aged ; Treatment Outcome ; Young Adult ; beta-Lactamase Inhibitors/*administration &amp; dosage ; }, abstract = {Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity after exposure to amoxicillin-clavulanic acid (Amox-Clav). Ten healthy participants were enrolled. All received 5 days of Amox-Clav. Half were randomized to autoFMT, derived from stool collected pre-antimicrobial exposure, by enema, and half to saline enema. Participants submitted stool samples pre- and post-Amox-Clav and enema and during a 90-day follow-up period. Shotgun metagenomic sequencing revealed taxonomic composition, resistance gene content, and metabolic capacity. Amox-Clav significantly altered gut taxonomic composition in all participants (n = 10, P < 0.01); however, only three participants exhibited major changes at the phylum level following exposure. In the cohort as a whole, beta-lactamase genes were enriched following Amox-Clav (P < 0.05), and predicted metabolic capacity was significantly altered (P < 0.01). Species composition, metabolic capacity, and beta-lactamase abundance returned to pre-antimicrobial exposure state 7 days after either autoFMT or saline enema (P > 0.05, compared to enrollment). Alterations to microbial metabolic capacity occurred following antimicrobial exposure even in participants without substantial taxonomic disruption, potentially creating open niches for pathogen colonization. Our findings suggest that metabolic potential is an important consideration for complete assessment of antimicrobial impact on the microbiome. AutoFMT was well tolerated and may have contributed to phylogenetic recovery. (This study has been registered at ClinicalTrials.gov under identifier NCT02046525.)IMPORTANCE The spread of multidrug resistance among pathogenic organisms threatens the efficacy of antimicrobial treatment options. The human gut serves as a reservoir for many drug-resistant organisms and their resistance genes, and perturbation of the gut microbiome by antimicrobial exposure can open metabolic niches to resistant pathogens. Once established in the gut, antimicrobial-resistant bacteria can persist even after antimicrobial exposure ceases. Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of amoxicillin-clavulanic acid (Amox-Clav) exposure and autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity. Importantly, we found that metabolic capacity was perturbed even in cases where gross phylogeny remained unchanged and that autoFMT was safe and well tolerated.}, }
@article {pmid30463736, year = {2018}, author = {Kuehn, F and Adiliaghdam, F and Hamarneh, SR and Vasan, R and Liu, E and Liu, Y and Ramirez, JM and Hoda, RS and Munoz, AR and Ko, FC and Armanini, M and Brooks, DJ and Bouxsein, ML and Demay, MB and Hodin, RA}, title = {Loss of Intestinal Alkaline Phosphatase Leads to Distinct Chronic Changes in Bone Phenotype.}, journal = {The Journal of surgical research}, volume = {232}, number = {}, pages = {325-331}, doi = {10.1016/j.jss.2018.06.061}, pmid = {30463736}, issn = {1095-8673}, support = {P30 AR066261/AR/NIAMS NIH HHS/United States ; }, mesh = {Alkaline Phosphatase/blood/*deficiency/genetics ; Animals ; Bone Remodeling/*physiology ; Cells, Cultured ; Duodenum/*metabolism ; Dysbiosis/metabolism ; Female ; Femur/diagnostic imaging/metabolism/*pathology ; Gastrointestinal Microbiome/physiology ; Intestinal Mucosa/*metabolism ; Macrophages ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Animal ; Primary Cell Culture ; RNA, Messenger/isolation &amp; purification/metabolism ; Real-Time Polymerase Chain Reaction ; Specific Pathogen-Free Organisms ; X-Ray Microtomography ; }, abstract = {BACKGROUND: The gut is becoming increasingly recognized as the source of various systemic diseases, and recently, it has been linked to bone metabolism via the so-called gut-bone axis. The microbiome and gut-derived mediators are thought to impact upon bone metabolism, and administration of probiotics has been shown to have beneficial effects in bone. The gut brush border enzyme intestinal alkaline phosphatase (IAP) plays an important role in controlling calcium absorption, inhibiting lipopolysaccharides, and other inflammatory mediators responsible for endotoxemia and appears to preserve the normal gut microbiota. Interestingly, IAP-deficient mice (AKP3[-/-]) also display a significant decrease in fecal Lactobacillus, the genus shown to be beneficial to bone.<br><br>MATERIALS AND METHODS: IAP mRNA levels in mouse bone were measured using quantitative real-time polymerase chain reaction. Femurs of IAP-knockout (KO) and wild-type (WT) mice were analyzed by microcomputed tomography and histopathology. Serum levels of alkaline phosphatase, calcium, and phosphorus were measured. Target cell response upon exposure to serum from IAP-KO and WT mice was quantified using primary bone marrow macrophages.<br><br>RESULTS: IAP was not significantly expressed in bones of WT or KO animals. IAP (alkaline phosphatase 3) expression in bone was vanishingly low compared to the duodenum (bone versus duodenum, 56.9&#xa0;&#xb1;&#xa0;17.7 versus 25,430.3&#xa0;&#xb1;&#xa0;10,884.5 relative expression, P&#xa0;=&#xa0;0.01). Bone histology of younger IAP-KO and WT animals was indistinguishable, whereas older IAP-deficient mice showed a distinctly altered phenotype on histology and computed tomography scan. Younger KO mice did not display any abnormal levels in blood chemistry. Older IAP-KO animals showed an isolated increase in serum alkaline phosphatase levels reflecting an environment of active bone formation (IAP-WT versus IAP-KO, 80&#xa0;&#xb1;&#xa0;27.4 U/I versus 453&#xa0;&#xb1;&#xa0;107.5 U/I, P&#xa0;=&#xa0;0.004). There was no significant difference in serum calcium or phosphorus levels between KO and WT mice. Serum from IAP-KO mice induced a significantly higher inflammatory target cell response.<br><br>CONCLUSIONS: Through its multiple functions, IAP seems to play a crucial role in connecting the gut to the bone. IAP deficiency leads to chronic changes in bone formation, most likely through dysbiosis and systemic dissemination of proinflammatory mediators.}, }
@article {pmid30462346, year = {2019}, author = {Chemouny, JM and Gleeson, PJ and Abbad, L and Lauriero, G and Boedec, E and Le Roux, K and Monot, C and Bredel, M and Bex-Coudrat, J and Sannier, A and Daugas, E and Vrtovsnik, F and Gesualdo, L and Leclerc, M and Berthelot, L and Ben Mkaddem, S and Lepage, P and Monteiro, RC}, title = {Modulation of the microbiota by oral antibiotics treats immunoglobulin A nephropathy in humanized mice.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {34}, number = {7}, pages = {1135-1144}, doi = {10.1093/ndt/gfy323}, pmid = {30462346}, issn = {1460-2385}, mesh = {Animals ; Female ; Male ; Mice ; Administration, Oral ; *Anti-Bacterial Agents/administration &amp; dosage ; Disease Models, Animal ; *Gastrointestinal Microbiome/drug effects ; *Glomerulonephritis, IGA/drug therapy/immunology/microbiology ; }, abstract = {BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. IgA is mainly produced by the gut-associated lymphoid tissue (GALT). Both experimental and clinical data suggest a role of the gut microbiota in this disease. We aimed to determine if an intervention targeting the gut microbiota could impact the development of disease in a humanized mouse model of IgAN, the α1KI-CD89Tg mice.<br><br>METHODS: Four- and 12-week old mice were divided into two groups to receive either antibiotics or vehicle control. Faecal bacterial load and proteinuria were quantified both at the beginning and at the end of the experiment, when blood, kidneys and intestinal tissue were collected. Serum mouse immunoglobulin G (mIgG) and human immunoglobulin A1 (hIgA1)-containing complexes were quantified. Renal and intestinal tissue were analysed by optical microscopy after haematoxylin and eosin colouration and immunohistochemistry with anti-hIgA and anti-mouse CD11b antibodies.<br><br>RESULTS: Antibiotic treatment efficiently depleted the faecal microbiota, impaired GALT architecture and impacted mouse IgA production. However, while hIgA1 and mIgG serum levels were unchanged, the antibiotic treatment markedly prevented hIgA1 mesangial deposition, glomerular inflammation and the development of proteinuria. This was associated with a significant decrease in circulating hIgA1-mIgG complexes. Notably, final faecal bacterial load strongly correlated with critical clinical and pathophysiological features of IgAN such as proteinuria and hIgA1-mIgG complexes. In addition, treatment with broad-spectrum antibiotics reverted established disease.<br><br>CONCLUSIONS: These data support an essential role of the gut microbiota in the generation of mucosa-derived nephrotoxic IgA1 and in IgAN development, opening new avenues for therapeutic approaches in this disease.}, }
@article {pmid30462253, year = {2019}, author = {Riddle, MS and Connor, BA}, title = {Faecal microbiota transplantation: what is the role in travellers' diarrhoea?.}, journal = {Journal of travel medicine}, volume = {26}, number = {1}, pages = {}, doi = {10.1093/jtm/tay129}, pmid = {30462253}, issn = {1708-8305}, mesh = {Anti-Bacterial Agents ; *Clostridioides difficile ; *Colitis ; Diarrhea ; *Fascioliasis ; Fecal Microbiota Transplantation ; Humans ; Travel ; }, }
@article {pmid30460999, year = {2019}, author = {Koskenvuo, L and Malila, N and Pitkäniemi, J and Miettinen, J and Heikkinen, S and Sallinen, V}, title = {Sex differences in faecal occult blood test screening for colorectal cancer.}, journal = {The British journal of surgery}, volume = {106}, number = {4}, pages = {436-447}, pmid = {30460999}, issn = {1365-2168}, mesh = {Aged ; Colorectal Neoplasms/diagnosis/*mortality/surgery ; Early Detection of Cancer/*methods ; Female ; Finland ; Humans ; Male ; Middle Aged ; *Occult Blood ; Risk Assessment ; Sex Factors ; Survival Analysis ; }, abstract = {BACKGROUND: This analysis of patients in a randomized population-based health services study was done to determine the effects of faecal occult blood test (FOBT) screening of colorectal cancer (CRC) in outcomes beyond mortality, and to obtain explanations for potential sex differences in screening effectiveness.<br><br>METHODS: In the Finnish FOBT screening programme (2004-2011), people aged 60-69&#x2009;years were randomized into the screening and control arms. Differences in incidence, symptoms, tumour location, TNM categories, non-vital outcomes and survival in the screening and control arms were analysed.<br><br>RESULTS: From 321&#x2009;311 individuals randomized, 743 patients with screening-detected tumours and 617 control patients with CRC were analysed. CRC was less common in women than in men (0&#xb7;34 versus 0&#xb7;50 per cent; risk ratio (RR) 0&#xb7;82, 95 per cent c.i. 0&#xb7;74 to 0&#xb7;91) and women were less often asymptomatic (16&#xb7;7 versus 22&#xb7;0 per cent; RR 0&#xb7;76, 0&#xb7;61 to 0&#xb7;93). Women more often had right-sided tumours (32&#xb7;0 versus 21&#xb7;3 per cent; RR 1&#xb7;51, 1&#xb7;26 to 1&#xb7;80). Among men with left-sided tumours, those in the screening arm had lower N (RR 1&#xb7;23, 1&#xb7;02 to 1&#xb7;48) and M (RR 1&#xb7;57, 1&#xb7;14 to 2&#xb7;17) categories, as well as a higher overall survival rate than those in the control arm. Furthermore among men with left-sided tumours, non-radical resections (26&#xb7;2 versus 15&#xb7;7 per cent; RR 1&#xb7;67, 1&#xb7;22 to 2&#xb7;30) and postoperative chemotherapy sessions (61&#xb7;6 versus 48&#xb7;2 per cent; RR 1&#xb7;28, 1&#xb7;10 to 1&#xb7;48) were more frequent in the control arm. Similar benefits of screening were not detected in men with right-sided tumours or in women.<br><br>CONCLUSION: Biennial FOBT screening seems to be effective in terms of improving several different outcomes in men, but not in women. Differences in incidence, symptoms and tumour location may explain the differences in screening efficacy between sexes.}, }
@article {pmid30459320, year = {2018}, author = {Dugas, LR and Bernabé, BP and Priyadarshini, M and Fei, N and Park, SJ and Brown, L and Plange-Rhule, J and Nelson, D and Toh, EC and Gao, X and Dong, Q and Sun, J and Kliethermes, S and Gottel, N and Luke, A and Gilbert, JA and Layden, BT}, title = {Decreased microbial co-occurrence network stability and SCFA receptor level correlates with obesity in African-origin women.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {17135}, pmid = {30459320}, issn = {2045-2322}, support = {R01 DK080763/DK/NIDDK NIH HHS/United States ; R01 DK104927/DK/NIDDK NIH HHS/United States ; R01-DK111848//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/International ; R01-DK080763//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/International ; 1I01BX003382//U.S. Department of Veterans Affairs (VA)/International ; R01-Dk104927//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/International ; 080763//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/International ; R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK090360/DK/NIDDK NIH HHS/United States ; I01 BX003382/BX/BLRD VA/United States ; R01 DK111848/DK/NIDDK NIH HHS/United States ; }, mesh = {Adiposity ; Adult ; Black or African American ; Body Mass Index ; Diet, High-Fat/adverse effects ; Fatty Acids, Volatile/analysis/*metabolism ; Fecal Microbiota Transplantation ; *Feeding Behavior ; Female ; Gastrointestinal Microbiome/genetics/*physiology ; Ghana ; Humans ; Obesity/metabolism/*microbiology ; Receptors, Cell Surface/genetics ; Receptors, G-Protein-Coupled/genetics ; South Africa ; }, abstract = {We compared the gut microbial populations in 100 women, from rural Ghana and urban US [50% lean (BMI < 25 kg/m[2]) and 50% obese (BMI ≥ 30 kg/m[2])] to examine the ecological co-occurrence network topology of the gut microbiota as well as the relationship of short chain fatty acids (SCFAs) with obesity. Ghanaians consumed significantly more dietary fiber, had greater microbial alpha-diversity, different beta-diversity, and had a greater concentration of total fecal SCFAs (p-value < 0.002). Lean Ghanaians had significantly greater network density, connectivity and stability than either obese Ghanaians, or lean and obese US participants (false discovery rate (FDR) corrected p-value ≤ 0.01). Bacteroides uniformis was significantly more abundant in lean women, irrespective of country (FDR corrected p < 0.001), while lean Ghanaians had a significantly greater proportion of Ruminococcus callidus, Prevotella copri, and Escherichia coli, and smaller proportions of Lachnospiraceae, Bacteroides and Parabacteroides. Lean Ghanaians had a significantly greater abundance of predicted microbial genes that catalyzed the production of butyric acid via the fermentation of pyruvate or branched amino-acids, while obese Ghanaians and US women (irrespective of BMI) had a significantly greater abundance of predicted microbial genes that encoded for enzymes associated with the fermentation of amino-acids such as alanine, aspartate, lysine and glutamate. Similar to lean Ghanaian women, mice humanized with stool from the lean Ghanaian participant had a significantly lower abundance of family Lachnospiraceae and genus Bacteroides and Parabacteroides, and were resistant to obesity following 6-weeks of high fat feeding (p-value < 0.01). Obesity-resistant mice also showed increased intestinal transcriptional expression of the free fatty acid (Ffa) receptor Ffa2, in spite of similar fecal SCFAs concentrations. We demonstrate that the association between obesity resistance and increased predicted ecological connectivity and stability of the lean Ghanaian microbiota, as well as increased local SCFA receptor level, provides evidence of the importance of robust gut ecologic network in obesity.}, }
@article {pmid30458058, year = {2019}, author = {Chen, D and Wu, J and Jin, D and Wang, B and Cao, H}, title = {Fecal microbiota transplantation in cancer management: Current status and perspectives.}, journal = {International journal of cancer}, volume = {145}, number = {8}, pages = {2021-2031}, pmid = {30458058}, issn = {1097-0215}, support = {17JCYBJC24900//Tianjin Research Program of Application Foundation and Advanced Technology of China/International ; 81741075//National Natural Science Foundation of China/International ; 81570478//National Natural Science Foundation of China/International ; }, mesh = {Clostridioides difficile/physiology ; Clostridium Infections/microbiology/therapy ; Dysbiosis/microbiology/physiopathology ; Fecal Microbiota Transplantation/*methods/trends ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Microbiota/physiology ; Neoplasms/microbiology/*therapy ; Treatment Outcome ; }, abstract = {The human gut is home to a large and diverse microbial community, comprising about 1,000 bacterial species. The gut microbiota exists in a symbiotic relationship with its host, playing a decisive role in the host's nutrition, immunity and metabolism. Accumulating studies have revealed the associations between gut dysbiosis or some special bacteria and various cancers. Emerging data suggest that gut microbiota can modulate the effectiveness of cancer therapies, especially immunotherapy. Manipulating the microbial populations with therapeutic intent has become a hot topic of cancer research, and the most dramatic manipulation of gut microbiota refers to fecal microbiota transplantation (FMT) from healthy individuals to patients. FMT has demonstrated remarkable clinical efficacy against Clostridium difficile infection (CDI) and it is highly recommended for the treatment of recurrent or refractory CDI. Lately, interest is growing in the therapeutic potential of FMT for other diseases, including cancers. We briefly reviewed the current researches about gut microbiota and its link to cancer, and then summarized the recent preclinical and clinical evidence to indicate the potential of FMT in cancer management as well as cancer-treatment associated complications. We also presented the rationale of FMT for cancer management such as reconstruction of intestinal microbiota, amelioration of bile acid metabolism, and modulation of immunotherapy efficacy. This article would help to better understand this new therapeutic approach for cancer patients by targeting gut microbiota.}, }
@article {pmid30457100, year = {2019}, author = {Zheng, S and Ko, KKK and Chan, KS and Venkatachalam, I}, title = {Case Report: Diagnosis of Cryptosporidiosis in Renal Transplantation in a Low-Prevalence Setting.}, journal = {The American journal of tropical medicine and hygiene}, volume = {100}, number = {1}, pages = {78-80}, pmid = {30457100}, issn = {1476-1645}, mesh = {Adult ; Antiprotozoal Agents/therapeutic use ; Cryptosporidiosis/*diagnosis/drug therapy ; Cryptosporidium/genetics/*isolation &amp; purification ; Disease Management ; Feces/*parasitology ; High-Throughput Screening Assays ; Humans ; *Kidney Transplantation ; Male ; Molecular Diagnostic Techniques ; Prevalence ; Singapore ; }, abstract = {In high prevalence settings, cryptosporidiosis is commonly implicated as a cause of a gastroenteritis syndrome in the organ transplant population. Stool microscopy is predominant diagnostic modality. Therapeutic options in this group of patients are limited, making their management exceptionally challenging. We describe a case of a renal transplant recipient with cryptosporidiosis confirmed by the stool FilmArray gastrointestinal panel (GIP) nucleic acid-based assay and stool microscopy, describe our institutional experience in diagnosing cryptosporidiosis in a low-prevalence setting, and review the available literature on management of this condition in the organ transplant population. In a low-prevalence setting, the GIP can serve as a rapid screening tool in the diagnosis of cryptosporidiosis.}, }
@article {pmid30455884, year = {2018}, author = {Ohara, T and Suzutani, T}, title = {Efficacy of fecal microbiota transplantation in a patient with chronic intractable constipation.}, journal = {Clinical case reports}, volume = {6}, number = {11}, pages = {2029-2032}, pmid = {30455884}, issn = {2050-0904}, abstract = {We have presented the first case report of FMT therapy for a patient with chronic intractable constipation. This therapy resulted in good, medium-term outcomes. Follow-up analysis of the intestinal flora suggested that transplanted microbes from the donor, particularly Bifidobacterium and Clostridium cluster IX, may have been incorporated into the recipient.}, }
@article {pmid30455339, year = {2018}, author = {Weis, M}, title = {Impact of the gut microbiome in cardiovascular and autoimmune diseases.}, journal = {Clinical science (London, England : 1979)}, volume = {132}, number = {22}, pages = {2387-2389}, doi = {10.1042/CS20180410}, pmid = {30455339}, issn = {1470-8736}, mesh = {Animals ; Autoimmune Diseases/immunology/*microbiology/therapy ; Bacteria/*growth &amp; development/immunology ; Cardiovascular Diseases/immunology/*microbiology/therapy ; Dysbiosis ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Mice ; Probiotics/therapeutic use ; Species Specificity ; }, abstract = {The gut microbiome functions like an endocrine organ, generating enzymes and bioactive metabolites, which affect host physiology. In addition metabolism-independent processes like impaired intestinal barrier function may result in bacterial translocation and an increased inflammation. Specific microbe-associated molecular patterns (MAMPs) have been detected that induce immune activation via cognate pattern-recognition receptors on host immune cells, with subsequent consequences on inflammatory-induced endothelial dysfunction. Alterations in intestinal microbial and metabolic composition play an important role in human health and disease, including cardiovascular and autoimmune diseases. Changes in the composition of gut microbiota (dysbiosis) are linked to chronic inflammation, thrombosis, atherogenesis, chronic heart, and kidney disease, as well as to autoimmune diseases like systemic lupus erythematodes. Although non-selective approaches that broadly alter microbial community structure, such as prebiotics, probiotics, and fecal microbial transplantation, may have some promise, targeting defined microbial pathways and adjacent host immune responses may be the ultimate scientific goal.}, }
@article {pmid30450088, year = {2018}, author = {Li, X and Gao, X and Hu, H and Xiao, Y and Li, D and Yu, G and Yu, D and Zhang, T and Wang, Y}, title = {Clinical Efficacy and Microbiome Changes Following Fecal Microbiota Transplantation in Children With Recurrent Clostridium Difficile Infection.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2622}, pmid = {30450088}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) has been shown as an effective treatment for recurrent clostridium difficile infection (RCDI) in adults. In this study, we aim to evaluate the clinical efficacy of FMT in treating children with RCDI, and explore fecal microbiota changes during FMT treatment. A total of 11 RCDI subjects with a median age of 3.5 years were enrolled in this single-center prospective pilot study. All patients were cured (11/11, 100%) by FMT either through upper gastrointestinal tract route with a nasointestinal tube (13/16, 81.2%) or lower gastrointestinal tract route with a rectal tube (3/16, 18.8%). The cure rate of single FMT was 63.6% (7/11), and 4 (4/11, 36.4%) cases were performed with 2 or 3 times of FMT. Mild adverse events were reported in 4 children (4/11, 36.4%), including transient diarrhea, mild abdominal pain, transient fever and vomit. Gut microbiota composition analysis of 59 fecal samples collected from 34 participants (9 RCDI children, 9 donors and 16 health controls) showed that the alpha diversity was lower in pediatric RCDI patients before FMT than the healthy controls and donors, and fecal microbial community of pre-FMT samples (beta diversity) was apart from that of healthy controls and donors. No significant differences in alpha diversity, beta diversity or phylogenetic distance were detected between donors and healthy controls. Both the richness and diversity of gut microbiota were improved in the pediatric RCDI patients after FMT, and the bacteria community was shifted closer to the donor and healthy control group. Furthermore, FMT re-directed gut microbiome functions of pediatric RCDI toward a health state. Our results indicate that it is safe and tolerant to use FMT in treating pediatric RCDI. FMT shifted the gut microbiome composition and function in children with RCDI toward a healthy state.}, }
@article {pmid30449078, year = {2019}, author = {Sood, A and Mahajan, R and Juyal, G and Midha, V and Grewal, CS and Mehta, V and Singh, A and Joshi, MC and Narang, V and Kaur, K and Sidhu, H}, title = {Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis.}, journal = {Intestinal research}, volume = {17}, number = {1}, pages = {78-86}, pmid = {30449078}, issn = {1598-9100}, support = {IA/I/15/2/502086/WTDBT_/DBT-Wellcome Trust India Alliance/India ; }, abstract = {BACKGROUND/AIMS: Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC.<br><br>METHODS: This was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT.<br><br>RESULTS: Of 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation.<br><br>CONCLUSIONS: A multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal.}, }
@article {pmid30448982, year = {2019}, author = {Mazoyer, C and Treacy, P and Turchi, L and Lehur, PA and Benizri, E and Iannelli, A}, title = {Laparoscopic Roux-En-Y Gastric Bypass Versus Sleeve Gastrectomy on Pelvic Floor Disorders in Morbidly Obese Women: a Prospective Monocentric Pilot Study.}, journal = {Obesity surgery}, volume = {29}, number = {2}, pages = {609-616}, pmid = {30448982}, issn = {1708-0428}, mesh = {Adult ; Aged ; Fecal Incontinence/etiology/*surgery ; Female ; Flatulence ; *Gastrectomy ; *Gastric Bypass ; Humans ; Laparoscopy ; Middle Aged ; Obesity, Morbid/complications/surgery ; Pelvic Organ Prolapse/etiology/*surgery ; Pilot Projects ; Prospective Studies ; Urinary Incontinence/etiology/*surgery ; Young Adult ; }, abstract = {BACKGROUND: Obesity is a well-known risk factor for female pelvic floor disorders (PFD). This study assessed the effects of bariatric surgery (BS) on pelvic organ prolapse symptoms (POPs) and urinary (UI) and anal incontinence (AI) in morbidly obese women undergoing either sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB).<br><br>METHODS: Morbidly obese women undergoing BS from June 2016 to May 2017 were prospectively included. POPs, UI, and AI were compared at baseline and at 1&#xa0;year after surgery using validated questionnaires.<br><br>RESULTS: Seventy-two consecutive women were enrolled, 54 (75%) (30 (56%) RYBP and 24 (44%) SG) completed the study at 1&#xa0;year and were considered for the final analysis. The mean age and mean preoperative BMI were 43&#x2009;&#xb1;&#x2009;11.8&#xa0;years (range, 20-65) and 41&#x2009;&#xb1;&#x2009;5.4&#xa0;kg/m[2] (range, 35-56), respectively. At baseline, 30 (56%), 32 (59%), and 27 (50%) patients, respectively, had AI (flatus only 72%), UI, and POPs. The mean TBWL% at 1&#xa0;year was 33%. In the whole study population, weight loss was associated with a significant improvement in UI (p&#x2009;<&#x2009;0.001) but there was no significant difference in terms of AI and POPs. In the subgroups analysis, AI increased significantly 1&#xa0;year after the RYGB (p&#x2009;=&#x2009;0.02) due to an increase in flatus incontinence (p&#x2009;=&#x2009;0.04). No significant difference in AI was found 1&#xa0;year after the SG.<br><br>CONCLUSION: BS is associated with a significant improvement in UI but not in POPs. RYBP seems to increase AI, mainly flatus incontinence, compared to SG.}, }
@article {pmid30446486, year = {2018}, author = {Kaito, S and Toya, T and Yoshifuji, K and Kurosawa, S and Inamoto, K and Takeshita, K and Suda, W and Kakihana, K and Honda, K and Hattori, M and Ohashi, K}, title = {Fecal microbiota transplantation with frozen capsules for a patient with refractory acute gut graft-versus-host disease.}, journal = {Blood advances}, volume = {2}, number = {22}, pages = {3097-3101}, pmid = {30446486}, issn = {2473-9537}, mesh = {Acute Disease ; Bone Marrow Transplantation/adverse effects ; Capsules/chemistry ; Diarrhea/prevention &amp; control ; Enterococcus/genetics/isolation &amp; purification ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Freezing ; Glucocorticoids/therapeutic use ; Graft vs Host Disease/*diagnosis/drug therapy/etiology ; Humans ; Immunosuppressive Agents/therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Severity of Illness Index ; Young Adult ; }, abstract = {Bacterial diversity was restored after FMT with oral frozen capsules, with improvement of diarrhea. Oral FMT for steroid-refractory acute gGVHD is feasible and could be effective.}, }
@article {pmid30442907, year = {2019}, author = {Zhou, W and Chow, KH and Fleming, E and Oh, J}, title = {Selective colonization ability of human fecal microbes in different mouse gut environments.}, journal = {The ISME journal}, volume = {13}, number = {3}, pages = {805-823}, pmid = {30442907}, issn = {1751-7370}, support = {DP2 GM126893/GM/NIGMS NIH HHS/United States ; K22 AI119231/AI/NIAID NIH HHS/United States ; 1 DP2 GM126893-01//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/International ; }, mesh = {Animals ; Bacteroides/growth &amp; development/*physiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Genotype ; Humans ; *Metagenomics ; Mice ; Mice, Inbred C57BL ; }, abstract = {Mammalian hosts constantly interact with diverse exogenous microbes, but only a subset of the microbes manage to colonize due to selective colonization resistance exerted by host genetic factors as well as the native microbiota of the host. An important question in microbial ecology and medical science is if such colonization resistance can discriminate closely related microbial species, or even closely related strains of the same species. Using human-mouse fecal microbiota transplantation and metagenomic shotgun sequencing, we reconstructed colonization patterns of human fecal microbes in mice with different genotypes (C57BL6/J vs. NSG) and with or without an intact gut microbiota. We found that mouse genotypes and the native mouse gut microbiota both exerted different selective pressures on exogenous colonizers: human fecal Bacteroides successfully established in the mice gut, however, different species of Bacteroides selectively enriched under different gut conditions, potentially due to a multitude of functional differences, ranging from versatility in nutrient acquisition to stress responses. Additionally, different clades of Bacteroides cellulosilyticus strains were selectively enriched in different gut conditions, suggesting that the fitness of conspecific microbial strains in a novel host environment could differ.}, }
@article {pmid30431239, year = {2019}, author = {Berry, D}, title = {Up-close-and-personal with the human microbiome.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {17-19}, doi = {10.1111/1758-2229.12709}, pmid = {30431239}, issn = {1758-2229}, mesh = {Diet Therapy ; Drug Design ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/genetics/*physiology ; Genomics ; Humans ; Microbiota/drug effects/genetics/*physiology ; Phage Therapy ; }, }
@article {pmid30427836, year = {2018}, author = {Mazzawi, T and Lied, GA and Sangnes, DA and El-Salhy, M and Hov, JR and Gilja, OH and Hatlebakk, JG and Hausken, T}, title = {The kinetics of gut microbial community composition in patients with irritable bowel syndrome following fecal microbiota transplantation.}, journal = {PloS one}, volume = {13}, number = {11}, pages = {e0194904}, pmid = {30427836}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Aged ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Male ; *Microbiota ; Middle Aged ; Quality of Life ; Young Adult ; }, abstract = {BACKGROUND: Gut microbiota alterations are important in irritable bowel syndrome (IBS). The aim was to investigate the effect of fecal microbiota transplantation (FMT) on gut microbiota and the symptoms in patients with IBS.<br><br>MATERIAL AND METHODS: The study included 13 IBS patients according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered to the descending part of the duodenum via a gastroscope. Feces were collected from donors and patients before FMT, and from the patients at 1, 3 and 12 weeks and donors and patients at 20/28 weeks after FMT. Microbiota analysis was performed using GA-map Dysbiosis test (Genetic Analysis AS, Oslo, Norway). The patients completed the following questionnaires before and at the aforementioned weeks after FMT: IBS Symptom Questionnaire (IBS-SQ), IBS-Symptom Severity Scoring system (IBS-SSS), Short Form of Nepean Dyspepsia Index (SF-NDI), Bristol stool form scale, the Eysenck Personality Questionnaire-Neuroticism and Hospital Anxiety and Depression.<br><br>RESULTS: Donors and IBS patients had significantly different bacterial strain signals before FMT (Ruminococcus gnavus, Actinobacteria and Bifidobacteria) that became non-significant after 3 weeks following FMT. The changes in gut microbiota were similar between donors and patients at 20/28 weeks after FMT. Thus, patients' microbiota profiles became more-or-less similar to donors. The scores of all the questionnaires were significantly improved at all time points following FMT. No reported adverse effects.<br><br>CONCLUSIONS: FMT was associated with a change in gut microbiota and improvement in IBS symptoms and quality of life lasting for up to 28 weeks.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03333291.}, }
@article {pmid30424806, year = {2018}, author = {Kaliannan, K and Robertson, RC and Murphy, K and Stanton, C and Kang, C and Wang, B and Hao, L and Bhan, AK and Kang, JX}, title = {Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {205}, pmid = {30424806}, issn = {2049-2618}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Alkaline Phosphatase/biosynthesis ; Animals ; Bacterial Load ; Estradiol/*pharmacology ; Estrogens/*pharmacology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Isoflavones/pharmacology ; Lipopolysaccharides/biosynthesis ; Male ; Metabolic Syndrome/*prevention &amp; control ; Mice ; Mice, Inbred C57BL ; Proteobacteria/*metabolism ; *Sex Characteristics ; }, abstract = {BACKGROUND: Understanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS.<br><br>RESULTS: Here we show that gut microbiome mediates the preventive effect of estrogen (17&#x3b2;-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17&#x3b2;-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals. Interestingly, fecal microbiota-transplant from male mice transferred the MS phenotype to female mice, while antibiotic treatment eliminated the sexual dimorphism in MS, suggesting a causative role of the gut microbiome in this condition. Moreover, estrogenic compounds such as isoflavones exerted microbiome-modulating effects similar to those of 17&#x3b2;-estradiol and reversed symptoms of MS in the male mice. Finally, both expression and activity of intestinal alkaline phosphatase (IAP), a gut microbiota-modifying non-classical anti-microbial peptide, were upregulated by 17&#x3b2;-estradiol and isoflavones, whereas inhibition of IAP induced ME and LGCI in female mice, indicating a critical role of IAP in mediating the effects of estrogen on these parameters.<br><br>CONCLUSIONS: In summary, we have identified a previously uncharacterized microbiome-based mechanism that sheds light upon sexual dimorphism in the incidence of MS and that suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women.}, }
@article {pmid30423561, year = {2019}, author = {Cruz-Aguliar, RM and Wantia, N and Clavel, T and Vehreschild, MJGT and Buch, T and Bajbouj, M and Haller, D and Busch, D and Schmid, RM and Stein-Thoeringer, CK}, title = {An Open-Labeled Study on Fecal Microbiota Transfer in Irritable Bowel Syndrome Patients Reveals Improvement in Abdominal Pain Associated with the Relative Abundance of Akkermansia Muciniphila.}, journal = {Digestion}, volume = {100}, number = {2}, pages = {127-138}, doi = {10.1159/000494252}, pmid = {30423561}, issn = {1421-9867}, mesh = {Abdominal Pain/diagnosis/etiology/*therapy ; Adult ; Akkermansia ; DNA, Bacterial/isolation &amp; purification ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; Intestinal Mucosa/microbiology ; Irritable Bowel Syndrome/complications/microbiology/*therapy ; Male ; Pain Measurement ; Pilot Projects ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; Verrucomicrobia/genetics/*isolation &amp; purification ; Young Adult ; }, abstract = {BACKGROUND/AIMS: The gut microbiota is altered in irritable bowel syndrome (IBS), and microbiota manipulations by diet or antibiotics can reduce its symptoms. As fecal microbiota transfer (FMT) in IBS is still controversial, we investigated the clinical and side effects of FMT in a cohort of IBS patients with recurrent, treatment refractory symptoms, and studied gut microbiota signatures.<br><br>METHODS: Using an observational, prospective study design, we applied FMTs from one unrelated, healthy donor to 13 IBS patients. Fecal samples of patients and the donor were analyzed by 16S ribosomal RNA amplicon sequencing.<br><br>RESULTS: On a symptom level, primarily abdominal pain symptoms were reduced after FMT, and no adverse effects were observed. Studying the microbiome, we found an increase in alpha diversity and changes in the composition of the gut microbiota after FMT. Beta diversity changes after FMT were prominent in a subset of 7 patients with microbiota profiles coming very close to the donor. These patients also showed most pronounced visceral pain reduction. The relative abundance of Akkermansia muciniphila was inversely correlated with pain reduction in our cohort.<br><br>CONCLUSION: Although exploratory in nature and with a pilot character, this study highlights the potential role of microbiota manipulations in IBS and describes a novel association of intestinal Akkermansia and pain modulation.}, }
@article {pmid30420754, year = {2018}, author = {Wang, Y and Wiesnoski, DH and Helmink, BA and Gopalakrishnan, V and Choi, K and DuPont, HL and Jiang, ZD and Abu-Sbeih, H and Sanchez, CA and Chang, CC and Parra, ER and Francisco-Cruz, A and Raju, GS and Stroehlein, JR and Campbell, MT and Gao, J and Subudhi, SK and Maru, DM and Blando, JM and Lazar, AJ and Allison, JP and Sharma, P and Tetzlaff, MT and Wargo, JA and Jenq, RR}, title = {Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.}, journal = {Nature medicine}, volume = {24}, number = {12}, pages = {1804-1808}, pmid = {30420754}, issn = {1546-170X}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; CTLA-4 Antigen/antagonists &amp; inhibitors/immunology/therapeutic use ; Colitis/chemically induced/immunology/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*drug effects/immunology ; Humans ; Immune System/drug effects/microbiology ; Intestinal Mucosa/immunology/microbiology/pathology ; Ipilimumab/*adverse effects ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology/therapeutic use ; T-Lymphocytes, Regulatory/drug effects/immunology/microbiology ; }, abstract = {We report the first case series of immune checkpoint inhibitors (ICI)-associated colitis successfully treated with fecal microbiota transplantation, with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T-cells within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.}, }
@article {pmid30419580, year = {2018}, author = {Stallmach, A and Reuken, PA and Teich, N}, title = {[Advances in the diagnosis and treatment of Clostridioides [Clostridium] difficile infections in inflammatory bowel disease].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {56}, number = {11}, pages = {1369-1377}, doi = {10.1055/a-0729-3168}, pmid = {30419580}, issn = {1439-7803}, mesh = {*Clostridioides difficile ; *Clostridium Infections/complications/diagnosis/therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; *Inflammatory Bowel Diseases/complications ; Intestines ; }, abstract = {Patients with chronic inflammatory bowel disease (IBD) have a significantly increased risk of clinically relevant clostridial infection (CDI). In turn, CDI can increase IBD activity. Therefore, rapid diagnosis and therapy is required. Many diagnostic and treatment studies on patients with CDI without inflammatory bowel disease are not congruent with IBD patients. This overview summarizes the everyday data of recent years and condenses these into four guiding principles. 1) patients with IBD present a risk population for a CDI. A CDI not only worsens the disease activity in the short term, but also causes increased morbidity and mortality in the long term. 2) If a CDI is suspected, glutamate-dehydrogenase (GDH) detection should be carried out quickly. If this is positive, and the disease activity is high, a therapy against C. difficile already may be initiated and-if necessary-terminated in cases of negative confirmation tests. 3) IBD patients with a proven CDI should be treated primarily with vancomycin. 4) In a relapsing CDI, fecal microbiome transfer is an effective therapeutic measure. However, activation of the IBD must be expected in about 15 % of cases. Consistent adherence to these guidelines may help treat a CDI in IBD patients.}, }
@article {pmid30415447, year = {2019}, author = {Fang, X}, title = {Microbial treatment: the potential application for Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {40}, number = {1}, pages = {51-58}, pmid = {30415447}, issn = {1590-3478}, support = {81660203//National Natural Science Foundation of China/ ; 20142BAB205092//Natural Science Foundation of Jiangxi Province (CN)/ ; 20181BAB205030//Natural Science Foundation of Jiangxi Province (CN)/ ; }, mesh = {Animals ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Parkinson Disease/microbiology/*therapy ; Probiotics/*administration &amp; dosage ; Treatment Outcome ; }, abstract = {Alterations in the composition of the intestinal flora are associated with the pathophysiology of Parkinson's disease (PD). More importantly, the possible cause-effect links between gut flora and PD pathogenesis have been identified using PD animal models. Recent studies have found that probiotics improve the symptoms associated with constipation in PD patients. In addition, fecal microbiota transplantation (FMT) was recently shown to provide a protective effect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. Effective microbial therapy for PD includes probiotics and FMT. Therefore, microbial therapy may be a useful and novel approach for treatment of PD. In this review, I discuss the use of microbial treatment in PD.}, }
@article {pmid30414693, year = {2019}, author = {Prado, C and Michels, M and Ávila, P and Burger, H and Milioli, MVM and Dal-Pizzol, F}, title = {The protective effects of fecal microbiota transplantation in an experimental model of necrotizing enterocolitis.}, journal = {Journal of pediatric surgery}, volume = {54}, number = {8}, pages = {1578-1583}, doi = {10.1016/j.jpedsurg.2018.10.045}, pmid = {30414693}, issn = {1531-5037}, mesh = {Animals ; Disease Models, Animal ; Enterocolitis, Necrotizing/*therapy ; *Fecal Microbiota Transplantation ; Rats ; Rats, Wistar ; }, abstract = {BACKGROUND: Necrotizing enterocolitis (NEC) is a serious disease that affects premature neonates, causing high mortality. In the search for new options of treatment it was investigated whether fecal microbiota transplantation (FMT) decreased the inflammatory response during NEC development in experimental model.<br><br>METHODS: Wistar rats were used and divided as follows: na&#xef;ve, control (NEC induction), FMT-before (transplantation of microbiota before insult) and FMT-after (microbiota transplantation after insult). The microbiota transplantation was performed by administering a feces solution obtained from an adult donor rat. The induction of enterocolitis involves feeding by artificial formula, hypothermia, hypoxia and endotoxin administration. MPO activity, TNF-&#x3b1;, IL-1&#x3b2; and IL-6 levels, oxidative and nitrosative damage and the grade of intestinal mucosa lesion were analyzed.<br><br>RESULTS: The control group had a significant increase of inflammatory and oxidative parameters when compared to naive animals. Both FMT-before and after decreased all inflammatory and oxidative damage parameters when compared to control group. This was also true to the intestinal mucosa damage.<br><br>CONCLUSION: FMT administered just before or after NEC induction improved gut and systemic inflammation, and gut oxidative damage and intestinal injury.}, }
@article {pmid30409169, year = {2018}, author = {Ma, C and Sun, Z and Zeng, B and Huang, S and Zhao, J and Zhang, Y and Su, X and Xu, J and Wei, H and Zhang, H}, title = {Cow-to-mouse fecal transplantations suggest intestinal microbiome as one cause of mastitis.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {200}, pmid = {30409169}, issn = {2049-2618}, mesh = {Animals ; Bacteria/classification/genetics ; Cattle ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Mammary Glands, Animal/*microbiology ; Mastitis, Bovine/drug therapy/*microbiology ; Mice ; Probiotics/*therapeutic use ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Mastitis, which affects nearly all lactating mammals including human, is generally thought to be caused by local infection of the mammary glands. For treatment, antibiotics are commonly prescribed, which however are of concern in both treatment efficacy and neonate safety. Here, using bovine mastitis which is the most costly disease in the dairy industry as a model, we showed that intestinal microbiota alone can lead to mastitis.<br><br>RESULTS: Fecal microbiota transplantation (FMT) from mastitis, but not healthy cows, to germ-free (GF) mice resulted in mastitis symptoms in mammary gland and inflammations in serum, spleen, and colon. Probiotic intake in parallel with FMT from diseased cows led to relieved mastitis symptoms in mice, by shifting the murine intestinal microbiota to a state that is functionally distinct from either healthy or diseased microbiota yet structurally similar to the latter. Despite conservation in mastitis symptoms, diseased cows and mice shared few mastitis-associated bacterial organismal or functional markers, suggesting striking divergence in mastitis-associated intestinal microbiota among lactating mammals. Moreover, an "amplification effect" of disease-health distinction in both microbiota structure and function was apparent during the cow-to-mouse FMT.<br><br>CONCLUSIONS: Hence, dysbiosis of intestinal microbiota may be one cause of mastitis, and probiotics that restore intestinal microbiota function are an effective and safe strategy to treat mastitis.}, }
@article {pmid30408565, year = {2019}, author = {DeFilipp, Z and Hohmann, E and Jenq, RR and Chen, YB}, title = {Fecal Microbiota Transplantation: Restoring the Injured Microbiome after Allogeneic Hematopoietic Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {25}, number = {1}, pages = {e17-e22}, doi = {10.1016/j.bbmt.2018.10.022}, pmid = {30408565}, issn = {1523-6536}, mesh = {Allografts ; *Clostridioides difficile ; *Clostridium Infections/microbiology/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/microbiology/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; }, abstract = {Disruption of the intestinal microbiome early after allogeneic hematopoietic cell transplantation (allo-HCT) has been linked to adverse outcomes in transplant recipients. To date, whether microbiome-directed interventions will be able to impact important clinical endpoints remains unknown. Fecal microbiota transplantation (FMT) is a compelling intervention to restore healthy diversity to the intestinal microenvironment after allo-HCT, but currently has no established role in transplant recipients. In this review, we examine the use of FMT as treatment for Clostridium difficile infection and acute graft-versus-host disease, and also as a restorative intervention early after allo-HCT. Ongoing and planned studies will help determine the ultimate role of FMT in allo-HCT recipients.}, }
@article {pmid30407465, year = {2018}, author = {Rojo-Medina, J and Ruiz-Matus, C and Salazar-Schettino, PM and González-Roldán, JF}, title = {[Enfermedad de Chagas en México].}, journal = {Gaceta medica de Mexico}, volume = {154}, number = {5}, pages = {605-612}, doi = {10.24875/GMM.18004515}, pmid = {30407465}, issn = {0016-3813}, mesh = {Chagas Disease/*epidemiology/prevention &amp; control/transmission ; Female ; Humans ; Incidence ; Infectious Disease Transmission, Vertical/prevention &amp; control ; Mass Screening/*methods ; Mexico/epidemiology ; Organ Transplantation/adverse effects ; Pregnancy ; Pregnancy Complications, Parasitic/epidemiology ; Transfusion Reaction/epidemiology/parasitology/prevention &amp; control ; Trypanosoma cruzi/*isolation &amp; purification ; }, abstract = {Chagas disease, which is caused by Trypanosoma cruzi, is considered to be the most serious parasitic disease in America. It is transmitted mainly by triatominae ("kissing bugs"). Mazzoti reported the first two human cases in Mexico. The form of transmission is by parasites entering the organism in feces of the insect, by blood transfusion, from mother to child, by organ transplant and laboratory accidents. In Mexico, 1.1 million people are estimated to be infected; the incidence in 2012 was 0.70 per 1,00,000 population. In 2017, the highest incidence rates were registered in Yucatán, Oaxaca and Hidalgo. The infection causes cardiomyopathies and mega-organs of the digestive tract. Diagnosis in the acute phase is by parasitological approach and, in the chronic phase, by laboratory screening studies. In Mexico's blood banks, screening for Chagas disease is mandatory; from 2007 to 2016, seroprevalence has decreased from 0.40 to 0.32 due to the improvement of donor selection processes and the ad hoc questionnaire. The targets of the parasite are neurons and smooth and myocardial muscle cells. The association of neuronal and smooth muscle destruction defines the presentation of chagas mega-syndromes. Initial manifestations of the disease can go unnoticed; 5% show apparent signs and symptoms and 30% will progress to the chronic asymptomatic phase. Currently available treatments have effect in the acute phase. For the control of Chagas disease, the Specific Action Program for the Prevention and Control of Chagas Disease (PAE Chagas 2013-2018) is available to initiate activities aimed at eliminating transfusion and congenital transmission and controlling vector transmission. The success of medical care depends on oportune detection, early etiological treatment and coverage broadening. On the other hand, monitoring and screening of pregnant women living in risk areas and blood and organ donors universal screening will enable the elimination congenital and transfusion transmission.}, }
@article {pmid30405910, year = {2018}, author = {Niccum, BA and Stein, DJ and Behm, BW and Hays, RA}, title = {Zinc Deficiency and the Recurrence of Clostridium difficile Infection after Fecal Microbiota Transplant: A Retrospective Cohort Study.}, journal = {Journal of nutrition and metabolism}, volume = {2018}, number = {}, pages = {9682975}, pmid = {30405910}, issn = {2090-0724}, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridium difficile infection (CDI). However, in 12% of patients treated with FMT, CDI recurs within one month. Zinc deficiency predicts increased diarrheal frequency in malnourished children, but little is known about its association with FMT outcome. We hypothesized that zinc levels were an independent predictor of CDI recurrence after FMT.<br><br>METHODS: We performed a retrospective cohort study of 80 patients (mean age, 66; 59 women) receiving FMT for CDI from 9/2013-9/2016 at a tertiary care center. Zinc levels were measured within 90 days before FMT. The primary outcome was CDI recurrence within 90 days after FMT. We controlled for risk factors for FMT failure using Cox regression. We also analyzed the effect of zinc supplementation in individuals with deficiency.<br><br>RESULTS: Forty-nine subjects had a normal zinc level, and 31 had a low level (<0.66&#x2009;&#xb5;g/mL). CDI recurred in 3/49 (6%) patients with normal zinc and 5/31 (16%) patients with low zinc (HR&#x2009;=&#x2009;11.327, 95% CI&#x2009;=&#x2009;2.162-59.336, p=0.004). Among low zinc subjects, 2 of 25 (8%) that received zinc supplements and 3 of 6 (50%) that did not receive zinc supplements had recurrence of CDI (HR&#x2009;=&#x2009;0.102, 95% CI&#x2009;=&#x2009;0.015-0.704, p=0.021).<br><br>CONCLUSION: Zinc deficiency was associated with increased CDI recurrence after FMT. Among zinc-deficient patients, supplementation was associated with reduced recurrence. Further study is needed to determine whether zinc deficiency represents a pathophysiologic mechanism and target for therapy.}, }
@article {pmid30404941, year = {2019}, author = {Morand, A and Cornu, F and Dufour, JC and Tsimaratos, M and Lagier, JC and Raoult, D}, title = {Human Bacterial Repertoire of the Urinary Tract: a Potential Paradigm Shift.}, journal = {Journal of clinical microbiology}, volume = {57}, number = {3}, pages = {}, pmid = {30404941}, issn = {1098-660X}, mesh = {Bacteria/classification/genetics/growth &amp; development/pathogenicity ; Bacterial Physiological Phenomena ; *Biodiversity ; Dysbiosis ; Gastrointestinal Microbiome ; Humans ; Microbiota ; Urinary Tract/*microbiology ; Urinary Tract Infections/microbiology ; Urine/*microbiology ; }, abstract = {The aim of this article is to review the human repertoire of bacteria in urine already described by culture and metagenomic techniques and published in the literature. Our study led us to compare this repertoire with other available human repertoires. We followed automatic and manual bibliographical methods and found 562 bacterial species reported in the literature as part of the human urinary microbiota. Of the 562 species, 322 were described only by culture, 101 by both culture and metagenomics, and 139 only by metagenomics. A total of 352 species (62.6%) have been associated with at least one case report of human infection, of which 225 (40.0%) have been described as causative agents of urinary tract infection. The urinary tract bacterial repertoire contains 21.4% of the known prokaryotic diversity associated with human beings (464 species in common), and it shares 23.6% species with the human gut microbiota (350 species in common, 62.3% of the urine species). The urinary repertoire shares a significant difference in aerointolerant species compared with those of the gut microbiota (100/562 [17.8%] and 505/1,484 [34.0%], respectively; P < 0.001; odds ratio [OR] = 9.0 [7.0 to 11.4]). Studies using high-throughput sequencing show a higher proportion of aerointolerant bacteria in urine (74/240 [30.8%]) than studies using culture techniques (40/423 [9.5%]). Most pathogenic bacteria are part of the commensal human urinary tract bacteria, and their pathogenicity may occur following any imbalance of this microbiota. The restoration of urinary tract health can occur following a fecal transplantation. The potential gut origin of the human bacterial microbiota has to be explored.}, }
@article {pmid30403550, year = {2019}, author = {Ooijevaar, RE and Terveer, EM and Verspaget, HW and Kuijper, EJ and Keller, JJ}, title = {Clinical Application and Potential of Fecal Microbiota Transplantation.}, journal = {Annual review of medicine}, volume = {70}, number = {}, pages = {335-351}, doi = {10.1146/annurev-med-111717-122956}, pmid = {30403550}, issn = {1545-326X}, mesh = {Clostridium Infections/diagnosis/*therapy ; Fecal Microbiota Transplantation/*methods/trends ; Female ; Forecasting ; Humans ; Irritable Bowel Syndrome/diagnosis/*therapy ; Male ; Patient Safety ; Randomized Controlled Trials as Topic ; Risk Assessment ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a well-established treatment for recurrent Clostridioides difficile infection. FMT has become a more readily available and useful new treatment option as a result of stool banks. The current state of knowledge indicates that dysbiosis of the gut microbiota is implicated in several disorders in addition to C. difficile infection. Randomized controlled studies have shown FMT to be somewhat effective in treating ulcerative colitis, irritable bowel syndrome, and hepatic encephalopathy. In addition, FMT has been beneficial in treating several other conditions, such as the eradication of multidrug-resistant organisms and graft-versus-host disease. We expect that FMT will soon be implemented as a treatment strategy for several new indications, although further studies are needed.}, }
@article {pmid30400734, year = {2019}, author = {Song, JH and Kim, YS}, title = {Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention.}, journal = {Gut and liver}, volume = {13}, number = {1}, pages = {16-24}, pmid = {30400734}, issn = {2005-1212}, mesh = {Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile ; Clostridium Infections/etiology/prevention &amp; control/*therapy ; Enterocolitis, Pseudomembranous/etiology/prevention &amp; control/*therapy ; Fecal Microbiota Transplantation/methods ; Humans ; Recurrence ; Risk Factors ; Secondary Prevention/*methods ; }, abstract = {The most common cause of antibiotic-associated diarrhea is Clostridium difficile infection (CDI). Recurrent C. difficile infection (rCDI) often occurs after successful treatment of CDI. Due to the increased incidence and the difficulty in treating rCDI, it is becoming an important clinical issue. Identifying risk factors is helpful for early detection, treatment, and prevention of rCDI. Advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulent strain are currently regarded as the major risk factors for rCDI. Several treatment modalities, including vancomycin, fidaxomicin, and fecal microbiota transplant (FMT), are suggested for rCDI treatment. However, there is currently no definitive treatment method with sufficient evidence for rCDI. Recent studies have focused on FMT and have shown positive results for rCDI. Prevention of rCDI by measures such as hand washing and isolation of patients is very important. However, these preventive measures are often overlooked in clinical practice. Here, we review the risk factors, treatment, and prevention of rCDI.}, }
@article {pmid30395128, year = {2018}, author = {Glass, D and Huang, DT and Dugum, M and Chintamaneni, P and Cua, S and Saul, M and Marsh, W and Al-Khafaji, A}, title = {Rectal Trumpet-Associated Hemorrhage in the Intensive Care Unit: A Quality Improvement Initiative.}, journal = {Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society}, volume = {45}, number = {6}, pages = {516-520}, doi = {10.1097/WON.0000000000000479}, pmid = {30395128}, issn = {1528-3976}, mesh = {APACHE ; Aged ; Catheterization/*adverse effects/nursing ; Fecal Incontinence/complications/*nursing ; Female ; Hemorrhage/epidemiology/physiopathology/*therapy ; Humans ; Intensive Care Units/organization &amp; administration/statistics &amp; numerical data ; Male ; Middle Aged ; Pennsylvania/epidemiology ; *Quality Improvement ; Rectum/blood supply/*injuries ; Retrospective Studies ; Surveys and Questionnaires ; }, abstract = {The rectal trumpet (RT) is a nasopharyngeal airway device that is inserted into the rectum for management of fecal incontinence. No published data exist on adverse events caused by the use of an RT. The purpose of this quality improvement project was to determine the rate of RT-associated hemorrhage among patients treated with an RT in our transplant intensive care unit (TICU). This quality improvement initiative and retrospective medical record review included all patients (N = 3933) cared for in a single specialty intensive care unit at a tertiary academic medical center between January 1, 2014, and May 31, 2016. We estimate that approximately 400 patients were treated with an RT. We found 3 possible and 9 probable cases of RT-associated hemorrhage, resulting in an estimated incident rate of 3% among RT-treated patients. All of these patients underwent invasive procedures for hemostasis. They received a mean of 4.9 units of packed red blood cell transfusions, and 9 experienced hypotension. Eight out of the 9 probable RT-associated hemorrhage patients experienced hemorrhage only after greater than 7 days of treatment with an RT. Following this initiative, RT use was banned in our TICU. The use of RTs can cause hemorrhage with clinically significant consequences.}, }
@article {pmid30388112, year = {2018}, author = {Jiang, ZD and Jenq, RR and Ajami, NJ and Petrosino, JF and Alexander, AA and Ke, S and Iqbal, T and DuPont, AW and Muldrew, K and Shi, Y and Peterson, C and Do, KA and DuPont, HL}, title = {Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.}, journal = {PloS one}, volume = {13}, number = {11}, pages = {e0205064}, pmid = {30388112}, issn = {1932-6203}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; UL1 TR000371/TR/NCATS NIH HHS/United States ; }, mesh = {Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Capsules ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; Cryopreservation ; Enema/adverse effects/*methods ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Freeze Drying ; Humans ; Male ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI).<br><br>AIMS: To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema.<br><br>METHODS: In a single center, adults with &#x2265; 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100-200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied.<br><br>RESULTS: Adverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema.<br><br>CONCLUSIONS: The route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT02449174.}, }
@article {pmid30385177, year = {2018}, author = {Peng, J and Xiao, X and Hu, M and Zhang, X}, title = {Interaction between gut microbiome and cardiovascular disease.}, journal = {Life sciences}, volume = {214}, number = {}, pages = {153-157}, doi = {10.1016/j.lfs.2018.10.063}, pmid = {30385177}, issn = {1879-0631}, mesh = {Cardiovascular Diseases/etiology/*microbiology/therapy ; Fatty Acids, Volatile/*metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Methylamines/*metabolism ; Probiotics/therapeutic use ; }, abstract = {Traditional cardiovascular risk factors do not underlie all incidence of cardiovascular disease. In recent years, accumulating evidence has demonstrated that gut microbiota and its metabolites also play a pivotal role in the onset and development of cardiovascular disease, including atherosclerosis, hypertension, heart failure, atrial fibrillation and myocardial fibrosis. Trillions of bacteria indwell the gastrointestinal tract and metabolize nutrients into trimethylamine-N-oxide, short-chain fatty acids and so on. Targeting these microorganisms and relevant metabolic pathways has beneficial effects in cardiovascular disease. This review will summarize the role of gut microbiota and its metabolites, mainly trimethylamine-N-oxide, in the pathogenesis of cardiovascular diseases, and discuss the possible mechanisms that drive cardiovascular diseases and highlight potential therapies in this field.}, }
@article {pmid30384952, year = {2018}, author = {Gopalsamy, SN and Woodworth, MH and Wang, T and Carpentieri, CT and Mehta, N and Friedman-Moraco, RJ and Mehta, AK and Larsen, CP and Kraft, CS}, title = {The Use of Microbiome Restoration Therapeutics to Eliminate Intestinal Colonization With Multidrug-Resistant Organisms.}, journal = {The American journal of the medical sciences}, volume = {356}, number = {5}, pages = {433-440}, pmid = {30384952}, issn = {1538-2990}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Infections/*prevention &amp; control ; Drug Resistance, Multiple, Bacterial/*physiology ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/*microbiology ; }, abstract = {Antibiotic resistance (AR) has been described by the World Health Organization as an increasingly serious threat to global public health. Many mechanisms of AR have become widespread due to global selective pressures such as widespread antibiotic use. The intestinal tract is an important reservoir for many multidrug-resistant organisms (MDROs), and next-generation sequencing has expanded understanding of the resistome, defined as the comprehensive sum of genetic determinants of AR. Intestinal decolonization has been explored as a strategy to eradicate MDROs with selective digestive tract decontamination and probiotics being notable examples with mixed results. This review focuses on fecal microbiota transplantation and the early evidence supporting its efficacy in decolonizing MDROs and potential mechanisms of action to reduce AR genes. Current evidence suggests that fecal microbiota transplantation may have promise in restoring healthy microbial diversity and reducing AR, and clinical trials are underway to better characterize its safety and efficacy.}, }
@article {pmid30384951, year = {2018}, author = {Stripling, J and Rodriguez, M}, title = {Current Evidence in Delivery and Therapeutic Uses of Fecal Microbiota Transplantation in Human Diseases-Clostridium difficile Disease and Beyond.}, journal = {The American journal of the medical sciences}, volume = {356}, number = {5}, pages = {424-432}, doi = {10.1016/j.amjms.2018.08.010}, pmid = {30384951}, issn = {1538-2990}, mesh = {Clostridioides difficile/*physiology ; Clostridium Infections/*history/therapy ; Enterocolitis, Pseudomembranous/history/therapy ; Fecal Microbiota Transplantation/*history ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; History, Medieval ; Humans ; }, abstract = {The use of fecal microbiota transplantation (FMT) was first described in China in the 4th century by Ge Hong when "yellow soup," a fecal slurry, was administered for the treatment of severe food poisoning and diarrhea, a practice that continued for centuries. Bedouin groups also consumed stools of their camels as a remedy for dysentery. FMT was also applied in veterinary medicine in Europe in the 16th century. Additional therapeutic use of human excretions was described in Europe in the 18th and 19th century and in World War II, when gut bacteria were administered to German soldiers suffering from dysentery in the North African campaign. More scientifically, Eismann, in 1958, utilized fecal transplantation via enema in 4 patients for the treatment of severe pseudomembranous colitis with success. Following this report a number of isolated cases were published describing the use of FMT by different delivery routes for the treatment of a variety of illnesses.}, }
@article {pmid30384948, year = {2018}, author = {Wilcox, CM}, title = {Study of the Microbiome Has Reached Prime Time.}, journal = {The American journal of the medical sciences}, volume = {356}, number = {5}, pages = {409-410}, doi = {10.1016/j.amjms.2018.08.006}, pmid = {30384948}, issn = {1538-2990}, mesh = {*Clostridioides difficile ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid30376869, year = {2018}, author = {Khoruts, A}, title = {Targeting the microbiome: from probiotics to fecal microbiota transplantation.}, journal = {Genome medicine}, volume = {10}, number = {1}, pages = {80}, pmid = {30376869}, issn = {1756-994X}, mesh = {Dietary Supplements ; *Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Molecular Targeted Therapy ; Probiotics/pharmacology ; }, abstract = {The modern techniques of microbiome science can be applied to the development and evaluation of all microbiota-directed products, including probiotics and fecal microbiota transplantation.}, }
@article {pmid30373736, year = {2018}, author = {Hassoun, A}, title = {Clostridium difficile associated disease.}, journal = {BMJ (Clinical research ed.)}, volume = {363}, number = {}, pages = {k4369}, doi = {10.1136/bmj.k4369}, pmid = {30373736}, issn = {1756-1833}, mesh = {Abdominal Pain/diagnosis ; Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/microbiology/therapy ; Diarrhea/diagnosis ; Digestive System Surgical Procedures ; Fecal Microbiota Transplantation ; Humans ; Practice Guidelines as Topic ; Recurrence ; Risk Factors ; }, }
@article {pmid30372516, year = {2018}, author = {Zare, A and Johansson, AM and Karlsson, E and Delhomme, N and Stenberg, P}, title = {The gut microbiome participates in transgenerational inheritance of low-temperature responses in Drosophila melanogaster.}, journal = {FEBS letters}, volume = {592}, number = {24}, pages = {4078-4086}, pmid = {30372516}, issn = {1873-3468}, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Cold Temperature ; Drosophila melanogaster/*genetics/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Gene Expression Profiling ; Inheritance Patterns/*genetics ; Male ; }, abstract = {Environmental perturbations induce transcriptional changes, some of which may be inherited even in the absence of the initial stimulus. Previous studies have focused on transfers through the germline although microbiota is also passed on to the offspring. Thus, we inspected the involvement of the gut microbiome in transgenerational inheritance of environmental exposures in Drosophila melanogaster. We grew flies in the cold versus control temperatures and compared their transcriptional patterns in both conditions as well as in their offspring. F2 flies grew in control temperature, while we controlled their microbiota acquisition from either F1 sets. Transcriptional status of some genes was conserved transgenerationally, and a subset of these genes, mainly expressed in the gut, was transcriptionally dependent on the acquired microbiome.}, }
@article {pmid30370307, year = {2018}, author = {Sun, W and Guo, Y and Zhang, S and Chen, Z and Wu, K and Liu, Q and Liu, K and Wen, L and Wei, Y and Wang, B and Chen, D}, title = {Fecal Microbiota Transplantation Can Alleviate Gastrointestinal Transit in Rats with High-Fat Diet-Induced Obesity via Regulation of Serotonin Biosynthesis.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {8308671}, pmid = {30370307}, issn = {2314-6141}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Diet, High-Fat/*adverse effects ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Transit/*physiology ; Male ; Obesity/*metabolism ; Rats ; Rats, Sprague-Dawley ; Serotonin/*metabolism ; }, abstract = {AIM: We tested the hypothesis that fecal microbiota transplantation (FMT) could regulate the biotransformation of bile acids, such as deoxycholic acid (DCA) and cholic acid (CA), which in turn regulate the biosynthesis of serotonin in the gut and relieve gastrointestinal dysmotility in high-fat diet- (HFD-) induced obesity in rats.<br><br>METHODS: Male Sprague-Dawley rats were randomly divided into the control diet group, HFD group, and HFD-fed with receiving FMT. HFD was fed for 12 weeks. At the end of two-week HFD, FMT was carried out for two weeks. The gastrointestinal transit, serotonin concentration, the expression of tryptophan hydroxylase 1 (TPH1) and serotonin reuptake transporter (SERT), and the levels of bile acids in intestinal contents were examined.<br><br>RESULTS: Compared with the control group, the gastrointestinal transit and small intestinal serotonin concentration of HFD-fed rats were increased. In HFD-fed rats, TPH1 protein expression was increased significantly, while SERT protein expression was decreased, but not significant. The levels of CA and DCA in intestinal contents were also significantly increased in HFD-fed rats compared with the control group. After HFD-fed rats receiving FMT treatment, the gastrointestinal transit, small intestinal serotonin concentration, and TPH1 expression were decreased, while SERT expression was not affected. Moreover, the levels of CA and DCA in intestinal contents were also decreased.<br><br>CONCLUSIONS: FMT could alleviate small intestinal transit in the HFD-fed rats by regulating the serotonin biosynthesis. In this process, CA and DCA may be related to the regulation of synthesis of serotonin.}, }
@article {pmid30367124, year = {2019}, author = {Brunse, A and Martin, L and Rasmussen, TS and Christensen, L and Skovsted Cilieborg, M and Wiese, M and Khakimov, B and Pieper, R and Nielsen, DS and Sangild, PT and Thymann, T}, title = {Effect of fecal microbiota transplantation route of administration on gut colonization and host response in preterm pigs.}, journal = {The ISME journal}, volume = {13}, number = {3}, pages = {720-733}, pmid = {30367124}, issn = {1751-7370}, mesh = {Animals ; Animals, Newborn ; Bacteria/genetics/isolation &amp; purification ; *Bacterial Adhesion ; Bacteroides/genetics/isolation &amp; purification ; Colon/microbiology ; Enterocolitis, Necrotizing/microbiology/prevention &amp; control/therapy/*veterinary ; Fecal Microbiota Transplantation/*veterinary ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/microbiology ; Hydrogen-Ion Concentration ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; Stomach/microbiology ; Swine ; Swine Diseases/microbiology/prevention &amp; control/*therapy ; }, abstract = {This study examined gut colonization patterns and host responses to fecal microbiota transplantation (FMT) by different administration routes after preterm birth. In two separate experiments, cesarean-delivered, preterm pigs were administered combined oral + rectal, or exclusively rectal donor feces, and compared with saline controls. After 5 days, stomach and colon bacterial compositions were determined by 16S rRNA gene amplicon sequencing, and organic acid metabolites measured. Further, gut pathology, mucosa bacterial adherence, and goblet cell density were assessed. FMT increased the relative abundance of obligate anaerobes in the colon without affecting total bacterial load. Bacteroides colonized recipients despite low abundance in the donor feces, whereas highly abundant Prevotella and Ruminococcaceae did not. Further, FMT changed carbohydrate metabolism from lactate to propionate production thereby increasing colonic pH. Besides, FMT preserved goblet cell mucin stores and reduced necrotizing enterocolitis incidence. Only rectal FMT increased the stomach-to-colon pH gradient and resistance to mucosa bacterial adhesion. Conversely, oral + rectal FMT increased bacterial adhesion, internal organ colonization, and overall mortality. Our results uncovered distinctions in bacterial colonization patterns along the gastrointestinal tract, as well as host tolerability between oral and rectal FMT administration in preterm newborns. Besides, FMT showed the potential to prevent necrotizing enterocolitis.}, }
@article {pmid30359194, year = {2018}, author = {Kiouptsi, K and Ruf, W and Reinhardt, C}, title = {Microbiota-Derived Trimethylamine.}, journal = {Circulation research}, volume = {123}, number = {10}, pages = {1112-1114}, doi = {10.1161/CIRCRESAHA.118.314039}, pmid = {30359194}, issn = {1524-4571}, mesh = {*Cation Transport Proteins ; Copper Transport Proteins ; Humans ; Methylamines ; *Microbiota ; *Thrombosis ; }, }
@article {pmid30359185, year = {2018}, author = {Skye, SM and Zhu, W and Romano, KA and Guo, CJ and Wang, Z and Jia, X and Kirsop, J and Haag, B and Lang, JM and DiDonato, JA and Tang, WHW and Lusis, AJ and Rey, FE and Fischbach, MA and Hazen, SL}, title = {Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis Potential.}, journal = {Circulation research}, volume = {123}, number = {10}, pages = {1164-1176}, pmid = {30359185}, issn = {1524-4571}, support = {R01 DK101674/DK/NIDDK NIH HHS/United States ; R01 DK106000/DK/NIDDK NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; DP1 DK113598/DK/NIDDK NIH HHS/United States ; R01 DK108259/DK/NIDDK NIH HHS/United States ; T32 HL134622/HL/NHLBI NIH HHS/United States ; S10 OD016346/OD/NIH HHS/United States ; R01 DK110174/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 HL126827/HL/NHLBI NIH HHS/United States ; T32 DK007470/DK/NIDDK NIH HHS/United States ; P01 HL030568/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Animals ; Bacterial Proteins/genetics/*metabolism ; Choline/metabolism ; Clostridium/enzymology/genetics ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Lyases/genetics/*metabolism ; Male ; Methylamines/metabolism ; Mice ; Mice, Inbred C57BL ; Middle Aged ; *Platelet Activation ; Thrombosis/blood/*microbiology ; }, abstract = {RATIONALE: Gut microbes influence cardiovascular disease and thrombosis risks through the production of trimethylamine N-oxide (TMAO). Microbiota-dependent generation of trimethylamine (TMA)-the precursor to TMAO-is rate limiting in the metaorganismal TMAO pathway in most humans and is catalyzed by several distinct microbial choline TMA-lyases, including the proteins encoded by the cutC/D (choline utilization C/D) genes in multiple human commensals.<br><br>OBJECTIVE: Direct demonstration that the gut microbial cutC gene is sufficient to transmit enhanced platelet reactivity and thrombosis potential in a host via TMA/TMAO generation has not yet been reported.<br><br>METHODS AND RESULTS: Herein, we use gnotobiotic mice and a series of microbial colonization studies to show that microbial cutC-dependent TMA/TMAO production is sufficient to transmit heightened platelet reactivity and thrombosis potential in a host. Specifically, we examine in vivo thrombosis potential employing germ-free mice colonized with either high TMA-producing stable human fecal polymcrobial communities or a defined CutC-deficient background microbial community coupled with a CutC-expressing human commensal&#xb1;genetic disruption of its cutC gene (ie, Clostridium sporogenes &#x394; cutC).<br><br>CONCLUSIONS: Collectively, these studies point to the microbial choline TMA-lyase pathway as a rational molecular target for the treatment of atherothrombotic heart disease.}, }
@article {pmid30357440, year = {2019}, author = {Li, P and Zhang, T and Xiao, Y and Tian, L and Cui, B and Ji, G and Liu, YY and Zhang, F}, title = {Timing for the second fecal microbiota transplantation to maintain the long-term benefit from the first treatment for Crohn's disease.}, journal = {Applied microbiology and biotechnology}, volume = {103}, number = {1}, pages = {349-360}, pmid = {30357440}, issn = {1432-0614}, support = {201502026//Special Scientific Research Fund of Public Welfare Profession of National Health and Family Planning Commission/ ; Zhang F//Jiangsu Province Creation Team and Leading Talents project/ ; 81670495//National Natural Science Foundation of China/ ; 81600417//National Natural Science Foundation of China/ ; 2015BAI13B07//National Clinical Research Center for Digestive Diseases/ ; BE2018751//Jiangsu Province Society Development project (CN)/ ; }, mesh = {Adult ; Crohn Disease/microbiology/*therapy ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Humans ; Male ; Middle Aged ; RNA, Ribosomal, 16S ; Time Factors ; Treatment Outcome ; Urinalysis/methods ; }, abstract = {Increasing evidence has shown that fecal microbiota transplantation (FMT) could be a promising treatment option for Crohn's disease (CD). However, the frequency of FMT for CD treatment remains unclear. This study aimed to evaluate the optimal timing for administering the second course of FMT to maintain the long-term clinical effects from the first FMT for patients with CD. Sixty-nine patients with active CD who underwent FMT twice and benefited from the first FMT were enrolled in this study. Clinical response, stool microbiota, and urine metabolome of patients were assessed during the follow-up. The median time of maintaining clinical response to the first FMT in total 69 patients was 125 days (IQR, 82.5-225.5). The time of maintaining clinical response to the second FMT in 56 of 69 patients was 176.5 days (IQR, 98.5-280). The fecal microbiota composition of each patient post the first FMT was closer to that of his/her donor. Compared to that of the baseline, patients prior to the second course of FMT showed significant differences in urinary metabolic profiles characterized by increased indoxyl sulfate, 4-hydroxyphenylacetate, creatinine, dimethylamine, glycylproline, hippurate, and trimethylamine oxide (TMAO). This study demonstrated that patients with CD could be administered the second course of FMT less than 4 months after the first FMT for maintaining the clinical benefits from the first FMT. This was supported by the host-microbial metabolism changes in patients with active CD. Trial registration: ClinicalTrials.gov , NCT01793831. Registered 18 February 2013. https://clinicaltrials.gov/ct2/show/NCT01793831?term=NCT01793831&amp;rank=1.}, }
@article {pmid30355801, year = {2018}, author = {Battaglioli, EJ and Hale, VL and Chen, J and Jeraldo, P and Ruiz-Mojica, C and Schmidt, BA and Rekdal, VM and Till, LM and Huq, L and Smits, SA and Moor, WJ and Jones-Hall, Y and Smyrk, T and Khanna, S and Pardi, DS and Grover, M and Patel, R and Chia, N and Nelson, H and Sonnenburg, JL and Farrugia, G and Kashyap, PC}, title = {Clostridioides difficile uses amino acids associated with gut microbial dysbiosis in a subset of patients with diarrhea.}, journal = {Science translational medicine}, volume = {10}, number = {464}, pages = {}, pmid = {30355801}, issn = {1946-6242}, support = {R03 DK111850/DK/NIDDK NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; K08 DK100638/DK/NIDDK NIH HHS/United States ; K23 DK103911/DK/NIDDK NIH HHS/United States ; P30 DK084567/DK/NIDDK NIH HHS/United States ; R01 DK114007/DK/NIDDK NIH HHS/United States ; R01 CA179243/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Amino Acids/*metabolism ; Animals ; Clostridioides difficile/*physiology ; Clostridium Infections/microbiology ; Diarrhea/complications/*microbiology ; Disease Susceptibility ; Dysbiosis/complications/*microbiology ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Male ; Mice ; Middle Aged ; Risk Factors ; Young Adult ; }, abstract = {The gut microbiota plays a critical role in pathogen defense. Studies using antibiotic-treated mice reveal mechanisms that increase susceptibility to Clostridioides difficile infection (CDI), but risk factors associated with CDI in humans extend beyond antibiotic use. Here, we studied the dysbiotic gut microbiota of a subset of patients with diarrhea and modeled the gut microbiota of these patients by fecal transplantation into germ-free mice. When challenged with C. difficile, the germ-free mice transplanted with fecal samples from patients with dysbiotic microbial communities showed increased gut amino acid concentrations and greater susceptibility to CDI. A C. difficile mutant that was unable to use proline as an energy source was unable to robustly infect germ-free mice transplanted with a dysbiotic or healthy human gut microbiota. Prophylactic dietary intervention using a low-proline or low-protein diet in germ-free mice colonized by a dysbiotic human gut microbiota resulted in decreased expansion of wild-type C. difficile after challenge, suggesting that amino acid availability might be important for CDI. Furthermore, a prophylactic fecal microbiota transplant in mice with dysbiosis reduced proline availability and protected the mice from CDI. Last, we identified clinical risk factors that could potentially predict gut microbial dysbiosis and thus greater susceptibility to CDI in a retrospective cohort of patients with diarrhea. Identifying at-risk individuals and reducing their susceptibility to CDI through gut microbiota-targeted therapies could be a new approach to preventing C. difficile infection in susceptible patients.}, }
@article {pmid30353027, year = {2018}, author = {Lai, ZL and Tseng, CH and Ho, HJ and Cheung, CKY and Lin, JY and Chen, YJ and Cheng, FC and Hsu, YC and Lin, JT and El-Omar, EM and Wu, CY}, title = {Fecal microbiota transplantation confers beneficial metabolic effects of diet and exercise on diet-induced obese mice.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {15625}, pmid = {30353027}, issn = {2045-2322}, mesh = {Animals ; *Diet, High-Fat ; *Fecal Microbiota Transplantation ; Feeding Behavior ; Gastrointestinal Microbiome ; Gene Expression Regulation ; Inflammation/genetics ; Male ; Mice, Inbred C57BL ; Mice, Obese ; *Physical Conditioning, Animal ; Principal Component Analysis ; }, abstract = {Diet and exercise are conventional methods for controlling body weight and are linked to alterations in gut microbiota. However, the associations of diet, exercise, and gut microbiota in the control of obesity remain largely unknown. In the present study, using 16S rRNA amplicon sequencing and fecal microbiota transplantation (FMT), normal fat diet (NFD), exercise and their combination resulted in improved metabolic profiles in comparison to sedentary lifestyle with high fat diet (HFD). Moreover, diet exerted more influence than exercise in shaping the gut microbiota. HFD-fed mice receiving FMT from NFD-exercised donors not only showed remarkably reduced food efficacy, but also mitigated metabolic profiles (p < 0.05). The transmissible beneficial effects of FMT were associated with bacterial genera Helicobacter, Odoribacter and AF12 and overrepresentation of oxidative phosphorylation and glycolysis genes. Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT, suggesting a potential therapeutic treatment for obesity.}, }
@article {pmid30345252, year = {2018}, author = {Yodoshi, T and Hurt, TL}, title = {Fecal Microbiota Transplantation to Patients with Refractory Very Early Onset Ulcerative Colitis.}, journal = {Pediatric gastroenterology, hepatology &amp; nutrition}, volume = {21}, number = {4}, pages = {355-360}, pmid = {30345252}, issn = {2234-8646}, abstract = {Recently, fecal microbiota transplantation (FMT) has been attracting attention as a possible medical treatment of ulcerative colitis (UC). A randomized controlled trial of FMT for children with UC is currently underway. Therapeutic effects of FMT for adults with UC remain controversial. We report two cases of early-onset UC in children. A patient was diagnosed with UC at age 1-year 9-month and underwent FMT at age 2-year 3-month. He attained clinical remission for three weeks after FMT, but then relapsed at four weeks, ultimately undergoing a total colectomy. Another child was diagnosed with UC at 2-year 10-month and she underwent FMT at age 5 years. She has remained in clinical remission following FMT for 24 months and her UC has been maintained without complications with tacrolimus and azathioprine. We report that FMT for early-onset UC appears to be safe and potentially effective.}, }
@article {pmid30342053, year = {2018}, author = {Vallianou, NG and Stratigou, T and Tsagarakis, S}, title = {Microbiome and diabetes: Where are we now?.}, journal = {Diabetes research and clinical practice}, volume = {146}, number = {}, pages = {111-118}, doi = {10.1016/j.diabres.2018.10.008}, pmid = {30342053}, issn = {1872-8227}, mesh = {Animals ; Diabetes Mellitus, Type 2/*microbiology ; Dysbiosis/*microbiology ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*genetics ; Humans ; Mice ; Prebiotics/*microbiology ; Probiotics/*metabolism ; }, abstract = {Alterations in the diversity or structure of gut microbiota known as dysbiosis, may affect metabolic activities, resulting in metabolic disorders, such as obesity and diabetes. The development of more sophisticated methods, such as metagenomics sequencing, PCR-denaturing gradient gel electrophoresis, microarrays and fluorescence in situ hybridization, has expanded our knowledge on gut microbiome. Dysbiosis has been related to increased plasma concentrations of gut microbiota-derived lipopolysaccharide (LPS), which triggers the production of a variety of cytokines and the recruitment of inflammatory cells. Metabolomics have demonstrated that butyrate and propionate suppress weight gain in mice with high fat diet-induced obesity, and acetate has been proven to reduce food intake in healthy mice. The role of prebiotics, probiotics, genetically modified bacteria and fecal microbiota transplantation, as potential therapeutic challenges for type 2 diabetes will be discussed in this review.}, }
@article {pmid30341117, year = {2018}, author = {Jitsumura, M and Cunningham, AL and Hitchings, MD and Islam, S and Davies, AP and Row, PE and Riddell, AD and Kinross, J and Wilkinson, TS and Jenkins, GJ and Williams, JG and Harris, DA}, title = {Protocol for faecal microbiota transplantation in ulcerative colitis (FMTUC): a randomised feasibility study.}, journal = {BMJ open}, volume = {8}, number = {10}, pages = {e021987}, pmid = {30341117}, issn = {2044-6055}, mesh = {Colitis, Ulcerative/*therapy ; Feasibility Studies ; Fecal Microbiota Transplantation/adverse effects/*methods ; *Gastrointestinal Microbiome ; Humans ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Remission Induction ; Single-Blind Method ; Treatment Outcome ; }, abstract = {BACKGROUND: The interaction of the gut microbiota with the human host is implicated in the pathogenesis of inflammatory and immunological diseases including ulcerative colitis (UC). Faecal microbiota transplantation (FMT) as a method of restoring gut microbial diversity is of increasing interest as a therapeutic approach in the management of UC. The current literature lacks consensus about the dose of FMT, route of administration and duration of response.<br><br>METHODS AND ANALYSIS: This single-blinded randomised trial will explore the feasibility of FMT in 30 treatment-na&#xef;ve patients with histologically confirmed distal UC limited to the recto-sigmoid region (up to 40&#x2009;cm from the anal verge). This study aims to estimate the magnitude of treatment response to FMT under controlled conditions. The intervention (FMT) will be administered by rectal retention enema. It will test the feasibility of randomising patients to: (i) single FMT dose, (ii) five daily FMT doses or (iii) control (no FMT dose). All groups will receive standard antibiotic gut decontamination and bowel preparation before FMT. Recruitment will take place over a 24-month period with a 12-week patient follow-up. Trial objectives include evaluation of the magnitude of treatment response to FMT, investigation of the clinical value of metabolic phenotyping for predicting the clinical response to FMT and testing the recruitment rate of donors and patients for a study in FMT. This feasibility trial will enable an estimate of number of patients needed, help determine optimal study conditions and inform the choice of endpoints for a future definitive phase III study.<br><br>ETHICS AND DISSEMINATION: The trial is approved by the regional ethics committee and is sponsored by Abertawe Bro Morgannwg University's Health Board. Written informed consent from all patients will be obtained. Serious adverse events will be reported to the sponsor. Trial results will be disseminated via peer review publication and shared with trial participants.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN 58082603; Pre-results.}, }
@article {pmid30339501, year = {2019}, author = {Elkrief, A and Derosa, L and Zitvogel, L and Kroemer, G and Routy, B}, title = {The intimate relationship between gut microbiota and cancer immunotherapy.}, journal = {Gut microbes}, volume = {10}, number = {3}, pages = {424-428}, pmid = {30339501}, issn = {1949-0984}, mesh = {Animals ; Antineoplastic Agents, Immunological/therapeutic use ; CTLA-4 Antigen/antagonists &amp; inhibitors ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/*immunology ; Host-Pathogen Interactions/immunology ; Humans ; *Immunotherapy ; Neoplasms/*immunology/*therapy ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; }, abstract = {Immunotherapy is widely used to treat a large variety of malignancies and has revolutionized the therapeutic approach to cancer. Major efforts are ongoing to identify biomarkers that predict response to immunotherapy as well as new strategies to improve ICI efficacy and clinical outcomes. Studies have shown that the gut microbiome determines the extent to which ICIs may invigorate the anticancer immune response. Here, the authors review recent studies that have described the effects of the gut microbiota on the efficacy of CTLA-4 and PD-1 inhibitors and outline potential future clinical directions of these findings.}, }
@article {pmid30338410, year = {2018}, author = {Chen, X and Devaraj, S}, title = {Gut Microbiome in Obesity, Metabolic Syndrome, and Diabetes.}, journal = {Current diabetes reports}, volume = {18}, number = {12}, pages = {129}, pmid = {30338410}, issn = {1539-0829}, mesh = {Animals ; Diabetes Mellitus/drug therapy/*microbiology ; *Gastrointestinal Microbiome/drug effects ; Humans ; Hypoglycemic Agents/pharmacology/therapeutic use ; Insulin Resistance ; Metabolic Syndrome/*microbiology ; Obesity/*microbiology ; }, abstract = {PURPOSE OF REVIEW: Obesity and diabetes are worldwide epidemics. There is also a growing body of evidence relating the gut microbiome composition to insulin resistance. The purpose of this review is to delineate the studies linking gut microbiota to obesity, metabolic syndrome, and diabetes.<br><br>RECENT FINDINGS: Animal studies as well as proof of concept studies using fecal transplantation demonstrate the pivotal role of the gut microbiota in regulating insulin resistance states and inflammation. While we still need to standardize methodologies to study the microbiome, there is an abundance of evidence pointing to the link between gut microbiome, inflammation, and insulin resistance, and future studies should be aimed at identifying unifying mechanisms.}, }
@article {pmid30337038, year = {2018}, author = {Pesce, M and Borrelli, O and Saliakellis, E and Thapar, N}, title = {Gastrointestinal Neuropathies: New Insights and Emerging Therapies.}, journal = {Gastroenterology clinics of North America}, volume = {47}, number = {4}, pages = {877-894}, doi = {10.1016/j.gtc.2018.07.011}, pmid = {30337038}, issn = {1558-1942}, mesh = {Enteric Nervous System/*pathology/*physiopathology ; Gastrointestinal Diseases/diagnosis/*etiology/*therapy ; Gastrointestinal Motility/*physiology ; Humans ; }, abstract = {The bewildering complexity of the enteric nervous system makes it susceptible to develop a wide array of motility disorders, collectively called enteric neuropathies. These gastrointestinal conditions are among the most challenging to manage, mainly given poor characterization of their etiopathophysiology and outcomes. Not surprisingly, therefore, targeted or curative therapies for enteric neuropathies are lacking and management is largely symptomatic. Nonetheless, recent advances in neurogastroenterology have witnessed improvements in established strategies, such as intestinal transplantation and the emergence of new treatments including novel drugs, electrical pacing, and manipulation of fecal microbiota, as well as stem cell and gene therapy.}, }
@article {pmid30336371, year = {2018}, author = {Abravanel, F and Lacipière, A and Lhomme, S and Dubois, M and Minier, L and Peron, JM and Alric, L and Kamar, N and Izopet, J}, title = {Performance of a commercial assay for detecting and quantifying HEV RNA in faeces.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {109}, number = {}, pages = {1-5}, pmid = {30336371}, issn = {1873-5967}, mesh = {Diagnostic Tests, Routine/*methods/standards ; Feces/virology ; Hepatitis E/*diagnosis ; Hepatitis E virus/genetics/*isolation &amp; purification ; Humans ; RNA, Viral/analysis/genetics ; Reagent Kits, Diagnostic ; *Real-Time Polymerase Chain Reaction/standards ; Specimen Handling ; Viral Load/*methods/standards ; }, abstract = {BACKGROUND: Detecting hepatitis E virus (HEV) RNA in faeces is useful for diagnosing and monitoring HEV infections, particularly in immunocompromised patients requiring ribavirin therapy.<br><br>OBJECTIVES: This study evaluated the performance of the Altona RealStar HEV RNA kit for detecting and quantifying HEV in faeces.<br><br>STUDY DESIGN: RNA was extracted from 94 stool samples by two methods: QIAamp Viral RNA Mini kit and MagNA Pure 96 automate. The Altona results were compared to a reference laboratory-developed accredited ISO15189 RT-PCR assay.<br><br>RESULTS: The Altona and reference assays detect HEV RNA in 77/93 (82.8%) and 83/93 (89.2%) of the QIAamp extracted samples, respectively, after exclusion of invalid result; they detected HEV RNA in 67/92 (72.8%) and 66/92 (71.7%) of the MagNA Pure extracted samples, respectively, which emphasizes the importance of the RNA extraction method. The HEV RNA concentrations obtained with Altona RT-PCR and the reference RT-PCR were well correlated whatever the extraction method, and Bland Altman analyses indicated that the Altona values were higher than the reference assay values. The Altona values for QIAamp-extracted and MagNA Pure-extracted HEV RNA were very similar.<br><br>CONCLUSIONS: The Altona RealStar assay is suitable for quantifying HEV RNA in the faeces and monitoring HEV RNA shedding during ribavirin therapy. Extraction is critical for detecting faecal HEV with high performance RT-PCR assays.}, }
@article {pmid30335629, year = {2019}, author = {Dayananda, P and Wilcox, MH}, title = {Irritable bowel syndrome following Clostridium difficile infection.}, journal = {Current opinion in gastroenterology}, volume = {35}, number = {1}, pages = {1-5}, doi = {10.1097/MOG.0000000000000490}, pmid = {30335629}, issn = {1531-7056}, mesh = {Clostridium Infections/complications/immunology/*microbiology/physiopathology ; Dysbiosis/immunology/microbiology/physiopathology ; Gastrointestinal Microbiome/immunology ; Humans ; Irritable Bowel Syndrome/etiology/immunology/*microbiology/physiopathology ; Risk Factors ; }, abstract = {PURPOSE OF REVIEW: The aim of this review was to provide an overview of the current understanding of the diagnosis, pathophysiology, and the role of the gut microbiome in Clostridium difficile infection (CDI)-related postinfectious irritable bowel syndrome (PI-IBS).<br><br>RECENT FINDINGS: PI-IBS is a recognized pathological entity and was estimated to affect 1 in 10 patients with infectious enteritis. CDI remains a major healthcare burden worldwide with a one in four chance of recurrence of symptoms following treatment. While there is growing interest in functional gastrointestinal disorders including PI-IBS, studies examining the prevalence and risk factors of CDI-related PI-IBS remain scarce. One of many proposed mechanisms for PI-IBS is related to dysbiosis of the gut microbiota, which is the hallmark of CDI pathogenesis. Therefore, restoration of the gut microbiota, which is associated with successful outcomes in CDI, may be a potential treatment option for PI-IBS. However, two randomized controlled trails exploring the restoration of the gut microbiota using faecal microbiota transplant came to differing conclusions.<br><br>SUMMARY: PI-IBS, particularly CDI-related PI-IBS, remains an understudied area. A better understanding of the pathophysiology of PI-IBS is essential to developing more specific and effective management strategies.}, }
@article {pmid30328245, year = {2019}, author = {Lee, P and Yacyshyn, BR and Yacyshyn, MB}, title = {Gut microbiota and obesity: An opportunity to alter obesity through faecal microbiota transplant (FMT).}, journal = {Diabetes, obesity &amp; metabolism}, volume = {21}, number = {3}, pages = {479-490}, doi = {10.1111/dom.13561}, pmid = {30328245}, issn = {1463-1326}, mesh = {Blood Glucose/metabolism ; Dysbiosis/blood/complications/microbiology/therapy ; *Fecal Microbiota Transplantation ; Feeding Behavior/physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Metabolic Syndrome/blood/complications/microbiology/therapy ; Obesity/blood/complications/*microbiology/*therapy ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {Obesity is a global pandemic with immense health consequences for individuals and societies. Multiple factors, including environmental influences and genetic predispositions, are known to affect the development of obesity. Despite an increasing understanding of the factors driving the obesity epidemic, therapeutic interventions to prevent or reverse obesity are limited in their impact. Manipulation of the human gut microbiome provides a new potential therapeutic approach in the fight against obesity. Specific gut bacteria and their metabolites are known to affect host metabolism and feeding behaviour, and dysbiosis of this biosystem may lead to metabolic syndrome. Potential therapies to alter the gut microbiota to treat obesity include dietary changes, supplementation of the diet with probiotic organisms and prebiotic compounds that influence bacterial growth, and the use of faecal microbiota transplant, in which gut microbiota from healthy individuals are introduced into the gut. In this review, we examine the growing scientific evidence supporting the mechanisms by which the human gut microbiota may influence carbohydrate metabolism and obesity, and the various possible therapies that may utilize the gut microbiota to help correct metabolic dysfunction.}, }
@article {pmid30328062, year = {2018}, author = {Wang, H and Cui, B and Li, Q and Ding, X and Li, P and Zhang, T and Yang, X and Ji, G and Zhang, F}, title = {The Safety of Fecal Microbiota Transplantation for Crohn's Disease: Findings from A Long-Term Study.}, journal = {Advances in therapy}, volume = {35}, number = {11}, pages = {1935-1944}, pmid = {30328062}, issn = {1865-8652}, support = {81670495//China National Science Foundation/International ; 81600417//China National Science Foundation/International ; 2015BAI13B07//National Clinical Research Center for Digestive Diseases/International ; }, mesh = {Adult ; China/epidemiology ; Cohort Studies ; *Crohn Disease/diagnosis/epidemiology/therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Humans ; Male ; Middle Aged ; Patient Safety ; Prospective Studies ; Risk Assessment ; Risk Factors ; Severity of Illness Index ; Time ; Treatment Outcome ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) has been used as a potential treatment option for Crohn's disease (CD). However, there is still lack of safety and efficacy evidence based on large samples of CD undergoing FMT. This study aimed to evaluate the risk factors of adverse event (AE) in the long term and the efficacy of FMT in the short term for patients with CD.<br><br>METHODS: FMT via mid-gut for mild to severe CD in a single center trial (NCT01793831) was performed from October 2012 to December 2016. The possible factors with AE and efficacy after FMT were prospectively recorded.<br><br>RESULTS: A total of 184 frequencies of FMT were performed for 139 patients who received FMT. During 1&#xa0;month after FMT, 13.6% of mild AEs occurred, including increased frequency of defecation, fever, abdominal pain, flatulence, hematochezia, vomiturition, bloating and herpes zoster. No AE beyond 1&#xa0;month was observed. Therefore, a 1&#xa0;month cut-off could be suggested to define short-term and long-term AEs of FMT. Among the possible risk factors, only fecal microbiota purification methods were closely associated with the occurrence of&#xa0;AEs. The rate of AEs in patients undergoing manual methods for the preparation of fecal microbiota was 21.7%, which was significantly higher than the 8.7% in those experiencing an automatic method. The manual or automatic purification of fecal microbiota had no correlation with the efficacy of FMT.<br><br>CONCLUSION: This cohort study based on the largest size of cases demonstrated that improved fecal microbiota preparation reduced the rates of AEs, but did not affect the clinical efficacy in patients with CD.}, }
@article {pmid30325104, year = {2018}, author = {Tanveer, F and Younas, M and Fishbain, J}, title = {Lymphocytic choriomeningitis virus meningoencephalitis in a renal transplant recipient following exposure to mice.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {20}, number = {6}, pages = {e13013}, doi = {10.1111/tid.13013}, pmid = {30325104}, issn = {1399-3062}, mesh = {Adult ; Animals ; Feces/virology ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Kidney Failure, Chronic/surgery ; Kidney Transplantation/*adverse effects ; Lymphocytic Choriomeningitis/therapy/*transmission/virology ; Lymphocytic choriomeningitis virus/*isolation &amp; purification ; Male ; Meningoencephalitis/therapy/*transmission/virology ; Mice/*virology ; Physical Therapy Modalities ; Treatment Outcome ; }, abstract = {Solid organ transplant recipients (SOTR) are at increased risk for a wide variety of typical and atypical infections as a consequence of impaired cell mediated and humoral immunity. We report a case of meningoencephalitis in a renal transplant recipient caused by lymphocytic choriomeningitis virus (LCMV) acquired by exposure to mice excreta. The clinical course was complicated by the development of hydrocephalus, requiring a ventriculoperitoneal shunt. To our knowledge, this is the first reported case of LCMV infection in a SOTR that was not organ donor derived.}, }
@article {pmid30323765, year = {2018}, author = {Li, J and Cui, H and Cai, Y and Lin, J and Song, X and Zhou, Z and Xiong, W and Zhou, H and Bian, Y and Wang, L}, title = {Tong-Xie-Yao-Fang Regulates 5-HT Level in Diarrhea Predominant Irritable Bowel Syndrome Through Gut Microbiota Modulation.}, journal = {Frontiers in pharmacology}, volume = {9}, number = {}, pages = {1110}, pmid = {30323765}, issn = {1663-9812}, abstract = {Tong-Xie-Yao-Fang (TXYF) has been widely used for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in traditional Chinese medicine. However, its mechanism of action in the treatment of IBS-D remains to be fully understood. Recent reports have shown that Clostridium species in the gut can induce 5-HT production in the colon, which then contributes to IBS-D. Due to the wide use of TXYF in the clinical treatment of IBS-D and the close relationship between gut microbiota and IBS-D, we hypothesize that TXYF treats IBS-D by modulating gut microbiota and regulating colonic 5-HT levels. In this study, variation analysis of 16S rRNA was conducted to evaluate changes in the distribution of gut microbiota in IBS-D model rats after TXYF treatment. Moreover, we investigated whether TXYF could affect colonic 5-HT levels in IBS-D model rats. We then performed fecal transplantation experiments to confirm the effects of TXYF on gut microbiota and 5-HT levels. We found that TXYF treatment can ameliorate IBS-D and regulate 5-HT levels in colon tissue homogenates. TXYF treatment also affected the diversity of gut microbiota and altered the relative abundance of Akkermansia and Clostridium sensu stricto 1 in gut flora populations. Finally, we showed that fecal transplantation from TXYF-treated rats could relieve IBS-D and regulate 5-HT levels in colon tissue homogenates. In conclusion, the present study demonstrates that TXYF treatment diminishes colonic 5-HT levels and alleviates the symptoms of IBS-D by favorably affecting microbiota levels in gut flora communities.}, }
@article {pmid30320666, year = {2019}, author = {Cho, S and Spencer, E and Hirten, R and Grinspan, A and Dubinsky, MC}, title = {Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection in Pediatric Inflammatory Bowel Disease.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {68}, number = {3}, pages = {343-347}, doi = {10.1097/MPG.0000000000002172}, pmid = {30320666}, issn = {1536-4801}, mesh = {Adolescent ; Anti-Bacterial Agents/administration &amp; dosage ; Child ; Clostridium Infections/*complications/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Inflammatory Bowel Diseases/*complications ; Longitudinal Studies ; Male ; Recurrence ; Retrospective Studies ; Severity of Illness Index ; Vancomycin/administration &amp; dosage ; }, abstract = {OBJECTIVES: Recurrent Clostridium difficile infection (RCDI) increases morbidity and mortality in patients with inflammatory bowel disease (IBD). Fecal microbiota transplant (FMT) is known to be very effective for RCDI in non-IBD patients with cure rates up to 91%. The same success rates of FMT have not been reported in patients with IBD with RCDI, and the data in pediatrics are limited. We aimed to determine the effectiveness of FMT for RCDI in established pediatric patients with IBD.<br><br>METHODS: We performed a retrospective chart review of pediatric patients with IBD and RCDI (&#x2265;3 episodes) who underwent FMT via colonoscopy at a tertiary care IBD center. The primary outcome was the rate of RCDI within 60 days post-FMT. The secondary outcomes were recurrence rate by 6 months, rate of colectomy, and time to recurrence.<br><br>RESULTS: Of the 8 eligible patients, 6 had ulcerative colitis, 1 had IBD-unspecified, and 1 had Crohn disease. Median (interquartile range) age was 13 (11-14) years. All patients were on vancomycin at FMT. Two patients (25%) had RCDI by 60 days post-FMT and another 3 patients had RCDI between 60 days and 6 months. The median time to recurrence was 101 (40-139) days. Two patients (25%) who developed recurrence went to colectomy after FMT.<br><br>CONCLUSIONS: With a cure rate of 75% at 60 days, FMT administered for the treatment of RCDI may be an effective treatment option in pediatric IBD. However, there appears to be a significant rate of late recurrence of C difficile infection after 60 days in these patients.}, }
@article {pmid30320222, year = {2018}, author = {Cheng, S and Ma, X and Geng, S and Jiang, X and Li, Y and Hu, L and Li, J and Wang, Y and Han, X}, title = {Fecal Microbiota Transplantation Beneficially Regulates Intestinal Mucosal Autophagy and Alleviates Gut Barrier Injury.}, journal = {mSystems}, volume = {3}, number = {5}, pages = {}, pmid = {30320222}, issn = {2379-5077}, abstract = {Fecal microbiota transplantation (FMT) is one of the most effective ways to regulate the gut microbiota. Here, we investigated the effect of exogenous fecal microbiota on gut function from the perspective of analysis of the mucosal proteomes in a piglet model. A total of 289 differentially expressed proteins were annotated with 4,068 gene ontology (GO) function entries in the intestinal mucosa, and the levels of autophagy-related proteins in the forkhead box O (FoxO) signaling pathway were increased whereas the levels of proteins related to inflammation response were decreased in the recipient. Then, to assess the alleviation of epithelial injury in the Escherichia coli K88-infected piglets following FMT, intestinal microbiome-metabolome responses were determined. 16S rRNA gene sequencing showed that the abundances of beneficial bacteria, such as Lactobacillus and Succinivibrio, were increased whereas those of Enterobacteriaceae and Proteobacteria bacteria were decreased in the infected piglets following FMT. Metabolomic analysis revealed that levels of 58 metabolites, such as lactic acid and succinic acid, were enhanced in the intestinal lumen and that seven metabolic pathways, such as branched-chain amino acid metabolism pathways, were upregulated in the infected piglets following FMT. In concordance with the metabolome data, results of metagenomics prediction analysis also demonstrated that FMT modulated the metabolic functions of gut microbiota associated with linoleic acid metabolism. In addition, intestinal morphology was improved, a result that coincided with the decrease of intestinal permeability and the enhancement of mucins and mucosal expression of tight junction proteins in the recipient. Taken together, the results showed that FMT triggered intestinal mucosal protective autophagy and alleviated gut barrier injury through alteration of the gut microbial structure. IMPORTANCE The gut microbiota plays a crucial role in human and animal health, and its disorder causes multiple diseases. Over the past decade, FMT has gained increasing attention due to the success in treating Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). Although FMT appears to be effective, how FMT functions in the recipient remains unknown. Whether FMT exerts this beneficial effect through a series of changes in the host organism caused by alteration of gut microbial structure is also not known. In the present study, newborn piglets and E. coli K88-infected piglets were selected as models to explore the interplay between host and gut microbiota following FMT. Our results showed that FMT triggered intestinal mucosal autophagy and alleviated gut barrier injury caused by E. coli K88. This report provides a theoretical basis for the use of FMT as a viable therapeutic method for gut microbial regulation.}, }
@article {pmid30319644, year = {2018}, author = {Qi, X and Li, X and Zhao, Y and Wu, X and Chen, F and Ma, X and Zhang, F and Wu, D}, title = {Treating Steroid Refractory Intestinal Acute Graft-vs.-Host Disease With Fecal Microbiota Transplantation: A Pilot Study.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2195}, pmid = {30319644}, issn = {1664-3224}, mesh = {Acute Disease/therapy ; Adult ; Drug Resistance ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Glucocorticoids/*pharmacology/therapeutic use ; Graft vs Host Disease/immunology/mortality/*therapy ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Intestinal Diseases/immunology/mortality/*therapy ; Intestines/immunology/microbiology ; Male ; Middle Aged ; Pilot Projects ; Progression-Free Survival ; Prospective Studies ; Young Adult ; }, abstract = {Patients with steroid refractory gastrointestinal (GI) tract graft- vs.-host disease (GvHD) face a poor prognosis and limited therapeutic options. To accurately assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating steroid refractory GI tract GvHD, we conducted a pilot study involving eight patients. Having received FMTs, all patients' clinical symptoms relieved, bacteria enriched, and microbiota composition reconstructed. Compared to those who did not receive FMT, these eight patients achieved a higher progression-free survival. FMT can serve as a therapeutic option for GI tract aGVHD, but its effectiveness and safety need further evaluations. Clinical Trial Registration: NCT03148743.}, }
@article {pmid30319571, year = {2018}, author = {Zuo, T and Ng, SC}, title = {The Gut Microbiota in the Pathogenesis and Therapeutics of Inflammatory Bowel Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2247}, pmid = {30319571}, issn = {1664-302X}, abstract = {In the twenty first century, the changing epidemiology of inflammatory bowel disease (IBD) globally with increasing disease incidence across many countries relates to the altered gut microbiota, due to a combinatorial effect of environmental factors, human immune responses and genetics. IBD is a gastrointestinal disease associated with a gut microbial dysbiosis, including an expansion of facultative anaerobic bacteria of the family Enterobacteriaceae. Advances in high-throughput sequencing enable us to entangle the gut microbiota in human health and IBD beyond the gut bacterial microbiota, expanding insights into the mycobiota, virobiota and helminthes. Caudovirales (viruses) and Basidiomycota, Ascomycota, and Candida albicans (fungi) are revealed to be increased in IBD. The deconvolution of the gut microbiota in IBD lays the basis for unveiling the roles of these various gut microbiota components in IBD pathogenesis and being conductive to instructing on future IBD diagnosis and therapeutics. Here we comprehensively elucidate the alterations in the gut microbiota in IBD, discuss the effect of diets in the gut microbiota in relation to IBD, and illustrate the potential of manipulation of gut microbiota for IBD therapeutics. The therapeutic strategy of antibiotics, prebiotics, probiotics and fecal microbiota transplantation will benefit the effective application of precision microbiome manipulation in IBD.}, }
@article {pmid30317530, year = {2019}, author = {Adak, A and Khan, MR}, title = {An insight into gut microbiota and its functionalities.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {76}, number = {3}, pages = {473-493}, pmid = {30317530}, issn = {1420-9071}, support = {under Unit of Excellence Project (BT/550/NE/U-Excel/2014)//Department of Science and Technology, India/ ; }, mesh = {Computational Biology ; Gastrointestinal Microbiome/genetics/immunology/*physiology ; Gastrointestinal Tract/microbiology ; Humans ; Symbiosis ; }, abstract = {Gut microbiota has evolved along with their hosts and is an integral part of the human body. Microbiota acquired at birth develops in parallel as the host develops and maintains its temporal stability and diversity through adulthood until death. Recent developments in genome sequencing technologies, bioinformatics and culturomics have enabled researchers to explore the microbiota and in particular their functions at more detailed level than before. The accumulated evidences suggest that though a part of the microbiota is conserved, the dynamic members vary along the gastrointestinal tract, from infants to elderly, primitive tribes to modern societies and in different health conditions. Though the gut microbiota is dynamic, it performs some basic functions in the immunological, metabolic, structural and neurological landscapes of the human body. Gut microbiota also exerts significant influence on both physical and mental health of an individual. An in-depth understanding of the functioning of gut microbiota has led to some very exciting developments in therapeutics, such as prebiotics, probiotics, drugs and faecal transplantation leading to improved health.}, }
@article {pmid30310254, year = {2018}, author = {Camara-Lemarroy, CR and Metz, LM and Yong, VW}, title = {Focus on the gut-brain axis: Multiple sclerosis, the intestinal barrier and the microbiome.}, journal = {World journal of gastroenterology}, volume = {24}, number = {37}, pages = {4217-4223}, pmid = {30310254}, issn = {2219-2840}, mesh = {Animals ; Bile Acids and Salts/chemistry ; Brain/physiopathology ; Central Nervous System/physiology ; Clinical Trials as Topic ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Humans ; Immune System ; Intestines/physiology ; Multiple Sclerosis/*microbiology/*physiopathology ; Probiotics ; }, abstract = {The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.}, }
@article {pmid30306296, year = {2019}, author = {Schwenger, KJP and Bolzon, CM and Li, C and Allard, JP}, title = {Non-alcoholic fatty liver disease and obesity: the role of the gut bacteria.}, journal = {European journal of nutrition}, volume = {58}, number = {5}, pages = {1771-1784}, pmid = {30306296}, issn = {1436-6215}, mesh = {*Gastrointestinal Microbiome ; Humans ; Non-alcoholic Fatty Liver Disease/*complications/*microbiology ; Obesity/*complications/*microbiology ; }, abstract = {Non-alcoholic fatty-liver disease (NAFLD) is now considered one of the leading causes of liver disease worldwide and is associated with metabolic syndrome and obesity. There are several factors contributing to the disease state. Recent research suggests that the intestinal microbiota (IM) and bacterial products may play a role through several mechanisms which include increased energy uptake, intestinal permeability and chronic inflammation. In addition to diet and exercise, treatment options targeting the IM are being investigated and include the use of pre-, pro- and synbiotics as well as the possibility of fecal microbial transfers. This literature review explores the relationship between NAFLD and the IM as well as highlight new IM treatment options that may become available in the near future.}, }
@article {pmid30302341, year = {2018}, author = {Fang, H and Fu, L and Wang, J}, title = {Protocol for Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {8941340}, pmid = {30302341}, issn = {2314-6141}, mesh = {Adolescent ; Adult ; Child ; Cohort Studies ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Inflammatory Bowel Diseases/*therapy ; Middle Aged ; Publication Bias ; Randomized Controlled Trials as Topic ; Systematic Reviews as Topic ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging treatment approach for inflammatory bowel disease (IBD). The donor selection, the separation of fecal bacteria, the frequency of FMT, the way of infusion, the long-term safety, and efficacy are still uncertain.<br><br>AIM: To further study the efficacy and safety and protocol of FMT for IBD.<br><br>METHODS: A systematic review and meta-analysis were conducted until February, 2018. Clinical remission was established as the primary outcome.<br><br>RESULTS: A total of 596 paediatric and adult IBD patients were enrolled, and 459 patients received FMT therapy. 28.8% (132/459) patients achieved clinical remission during follow-up. 53% (241/459) patients achieved clinical response. The pooled estimated clinical remission for ulcerative colitis (UC) was 21% (95% CI: 8%-37%) and 30% (95% CI: 11%-52%) for Crohn's disease (CD), both with a risk of heterogeneity; 10% (95% CI: 0%-43%) for paediatric UC; 26% (95% CI: 10%-48%) for adult UC; 45% for paediatric CD (95% CI: 24%-66%); 22% (95% CI: 3%-52%) for adult CD. Meta-analysis of cohort studies showed that moderate-severe IBD patients could achieve more significant remission from FMT than mild-moderate patients (P=0.037). Delivery route has no impact on the efficacy of FMT in UC and CD. Based on current available evidence, a trend was observed towards higher clinical remission rate of frozen stool FMT than that of fresh stool for UC, while there was no significant difference between fresh and frozen FMT for CD. The optimal donor stool for FMT is still uncertain. Meta-analysis of RCTs showed that FMT treatment achieved significantly higher clinical remission rate than placebo for UC (28% versus 9%, P=0.0003).<br><br>CONCLUSION: FMT is an effective and safe therapy for both paediatric and adult IBD; fresh or frozen donor stool, delivery route, and antibiotic pretreatment or not have no impact on the efficacy of FMT in IBD. FMT might be a potential rescue therapy and even an initial standardized therapy for IBD. However, few data exist on long-term safety and efficacy and further validation is needed.}, }
@article {pmid30301167, year = {2018}, author = {Paule, A and Frezza, D and Edeas, M}, title = {Microbiota and Phage Therapy: Future Challenges in Medicine.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {6}, number = {4}, pages = {}, pmid = {30301167}, issn = {2076-3271}, abstract = {An imbalance of bacterial quantity and quality of gut microbiota has been linked to several pathologies. New strategies of microbiota manipulation have been developed such as fecal microbiota transplantation (FMT); the use of pre/probiotics; an appropriate diet; and phage therapy. The presence of bacteriophages has been largely underestimated and their presence is a relevant component for the microbiome equilibrium. As a promising treatment, phage therapy has been extensively used in Eastern Europe to reduce pathogenic bacteria and has arisen as a new method to modulate microbiota diversity. Phages have been selected and "trained" to infect a wide spectrum of bacteria or tailored to infect specific antibiotic resistant bacteria present in patients. The new development of genetically modified phages may be an efficient tool to treat the gut microbiota dysbiosis associated with different pathologies and increased production of bacterial metabolites and subsequently decrease systemic low-grade chronic inflammation associated with chronic diseases. Microbiota quality and mitochondria dynamics can be remodulated and manipulated by phages to restore the equilibrium and homeostasis of the system. Our aim is to highlight the great interest for phages not only to eliminate and control pathogenic bacterial infection but also in the near future to modulate the microbiota by adding new functions to selected bacteria species and rebalance the dynamic among phages and bacteria. The challenge for the medicine of tomorrow is to re-think and redesign strategies differently and far from our traditional thinking.}, }
@article {pmid30300561, year = {2018}, author = {Paknikar, R and Pekow, J}, title = {Fecal Microbiota Transplantation for the Management of Clostridium difficile Infection.}, journal = {Surgical infections}, volume = {19}, number = {8}, pages = {785-791}, pmid = {30300561}, issn = {1557-8674}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; }, mesh = {Clostridium Infections/complications/epidemiology/*therapy ; Dysbiosis/epidemiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Treatment Outcome ; United States/epidemiology ; }, abstract = {The clinical burden of Clostridium difficile infection (CDI) continues to grow. Despite the multitude of treatment options that have been developed and tested to combat the morbidity and death associated with CDI, recurrence remains common. As such, treatment modalities such as fecal microbiota transplantation (FMT) have become studied increasingly; FMT serves to transplant stool from carefully selected healthy subjects into C. difficile positive patients through a variety of delivery routes. In doing so, FMT is hypothesized to correct dysbiosis of the recipient gut microbiome addressing the root cause of the pathogenesis of C. difficile infection. A growing body of evidence shows FMT to be efficacious in this setting, and the study of FMT accordingly continues to evolve to identify novel indications for its utilization.}, }
@article {pmid30298433, year = {2019}, author = {Vemuri, R and Sylvia, KE and Klein, SL and Forster, SC and Plebanski, M and Eri, R and Flanagan, KL}, title = {The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility.}, journal = {Seminars in immunopathology}, volume = {41}, number = {2}, pages = {265-275}, pmid = {30298433}, issn = {1863-2300}, support = {HHSN272201400007C/AI/NIAID NIH HHS/United States ; T32 AI007417/AI/NIAID NIH HHS/United States ; U01 AI035042/AI/NIAID NIH HHS/United States ; U01 HL146201/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Disease Susceptibility/immunology/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; *Gastrointestinal Tract/immunology/microbiology ; Gonadal Steroid Hormones/*immunology ; Humans ; Male ; Peyer's Patches/*immunology ; *Sex Characteristics ; }, abstract = {Sex differences in immunity are well described in the literature and thought to be mainly driven by sex hormones and sex-linked immune response genes. The gastrointestinal tract (GIT) is one of the largest immune organs in the body and contains multiple immune cells in the GIT-associated lymphoid tissue, Peyer's patches and elsewhere, which together have profound effects on local and systemic inflammation. The GIT is colonised with microbial communities composed of bacteria, fungi and viruses, collectively known as the GIT microbiota. The GIT microbiota drives multiple interactions locally with immune cells that regulate the homeostatic environment and systemically in diverse tissues. It is becoming evident that the microbiota differs between the sexes, both in animal models and in humans, and these sex differences often lead to sex-dependent changes in local GIT inflammation, systemic immunity and susceptibility to a range of inflammatory diseases. The sexually dimorphic microbiome has been termed the 'microgenderome'. Herein, we review the evidence for the microgenderome and contemplate the role it plays in driving sex differences in immunity and disease susceptibility. We further consider the impact that biological sex might play in the response to treatments aimed at manipulating the GIT microbiota, such as prebiotics, live biotherapeutics, (probiotics, synbiotics and bacteriotherapies) and faecal microbial transplant. These alternative therapies hold potential in the treatment of both psychological (e.g., anxiety, depression) and physiological (e.g., irritable bowel disease) disorders differentially affecting males and females.}, }
@article {pmid30290648, year = {2018}, author = {Wen, W and Zhang, H and Shen, J and Wei, L and Shen, S}, title = {Fecal microbiota transplantation for patients with irritable bowel syndrome: A meta-analysis protocol.}, journal = {Medicine}, volume = {97}, number = {40}, pages = {e12661}, pmid = {30290648}, issn = {1536-5964}, mesh = {Fecal Microbiota Transplantation/*methods ; Humans ; Irritable Bowel Syndrome/*therapy ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Meta-Analysis as Topic ; }, abstract = {Irritable bowel syndrome (IBS) is a common functional bowel disease characterized by chronic or recurrent abdominal pain, bloating, constipation, and diarrhea. Many patients with IBS have a poor quality of life due to abdominal discomfort, diarrhea, constipation, and the presence of other diseases. At present, intestinal motility inhibitors, adsorbents, astringents, intestinal mucosal protective agents, and antidepressants have been combined to treat IBS, but the treatment process is long, which results in a large economic burden to patients. Fecal microbiota transplantation (FMT) is a treatment involving the transplantation of functional bacteria from healthy human feces into the gastrointestinal tract of patients; thus, replacing the intestinal flora and modulating intestinal and extra-intestinal diseases. In recent years, the efficacy and economic benefits of FMT in the treatment of IBS have received increasing attention from researchers.A search for randomized controlled trials (RCTs) on treating IBS with FMT will be performed using 9 databases, including PubMed, the Cochrane Library, Embase, ClinicalTrails, China National Knowledge Infrastructure, Sino Med, ScienceDirect, VIP, and Wanfang Data. Two reviewers will independently screen data extraction studies and assess study quality and risk of bias. The risk of bias for each RCT will be assessed against the Cochrane Handbook standards to assess methodological quality. RevMan V.5.3 software will be used to calculate data synthesis when meta-analysis is allowed.This study will provide a high-quality synthesis of existing evidence on the effectiveness and safety of FMT in the treatment of IBS.This study will determine if FMT is an effective and safe intervention for IBS.PROSPERO registration number is PROSPERO CRD42018108080.}, }
@article {pmid30289345, year = {2019}, author = {von Rosenvinge, EC and Palumbo, F and Ravel, J and Rowthorn, V and Hoffmann, D}, title = {The authors reply.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {113-114}, pmid = {30289345}, issn = {1949-0984}, mesh = {Feces ; *Microbiota ; }, abstract = {This is a reply to the commentary of Ossorio and Zhou.}, }
@article {pmid30288286, year = {2018}, author = {Ianiro, G and Maida, M and Burisch, J and Simonelli, C and Hold, G and Ventimiglia, M and Gasbarrini, A and Cammarota, G}, title = {Efficacy of different faecal microbiota transplantation protocols for Clostridium difficile infection: A systematic review and meta-analysis.}, journal = {United European gastroenterology journal}, volume = {6}, number = {8}, pages = {1232-1244}, pmid = {30288286}, issn = {2050-6406}, abstract = {BACKGROUND: Protocols for treating recurrent Clostridium difficile infection (rCDI) through faecal microbiota transplantation (FMT) are still not standardised. Our aim was to evaluate the efficacy of different FMT protocols for rCDI according to routes, number of infusions and infused material.<br><br>METHODS: MEDLINE, Embase, SCOPUS, Web of Science and the Cochrane Library were searched through 31 May 2017. Studies offering multiple infusions if a single infusion failed to cure rCDI were included. Data were combined through a random effects meta-analysis.<br><br>RESULTS: Fifteen studies (1150 subjects) were analysed. Multiple infusions increased efficacy rates overall (76% versus 93%) and in each route of delivery (duodenal delivery: 73% with single infusion versus 81% with multiple infusions; capsule: 80% versus 92%; colonoscopy: 78% versus 98% and enema: 56% versus 92%). Duodenal delivery and colonoscopy were associated, respectively, with lower efficacy rates (p&#x2009;=&#x2009;0.039) and higher efficacy rates (p&#x2009;=&#x2009;0.006) overall. Faecal amount&#x2009;&#x2264;&#x2009;50&#x2009;g (p&#x2009;=&#x2009;0.006) and enema (p&#x2009;=&#x2009;0.019) were associated with lower efficacy rates after a single infusion. The use of fresh or frozen faeces did not influence outcomes.<br><br>CONCLUSIONS: Routes, number of infusions and faecal dosage may influence efficacy rates of FMT for rCDI. These findings could help to optimise FMT protocols in clinical practice.}, }
@article {pmid30283097, year = {2018}, author = {Ramezani, A and Nolin, TD and Barrows, IR and Serrano, MG and Buck, GA and Regunathan-Shenk, R and West, RE and Latham, PS and Amdur, R and Raj, DS}, title = {Gut Colonization with Methanogenic Archaea Lowers Plasma Trimethylamine N-oxide Concentrations in Apolipoprotein e-/- Mice.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {14752}, pmid = {30283097}, issn = {2045-2322}, support = {U01 DK099914/DK/NIDDK NIH HHS/United States ; U01 DK099924/DK/NIDDK NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Aorta/metabolism/microbiology/pathology ; Apolipoproteins E/deficiency/*drug effects/genetics ; Atherosclerosis/microbiology/*prevention &amp; control ; Choline/administration &amp; dosage/metabolism ; Dietary Supplements ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Methane/metabolism ; Methanobrevibacter/growth &amp; development/*metabolism ; Methanosarcina/growth &amp; development/*metabolism ; Methylamines/administration &amp; dosage/*blood/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microbial Consortia/physiology ; Plaque, Atherosclerotic/microbiology/*prevention &amp; control ; }, abstract = {A mechanistic link between trimethylamine N-oxide (TMAO) and atherogenesis has been reported. TMAO is generated enzymatically in the liver by the oxidation of trimethylamine (TMA), which is produced from dietary choline, carnitine and betaine by gut bacteria. It is known that certain members of methanogenic archaea (MA) could use methylated amines such as trimethylamine as growth substrates in culture. Therefore, we investigated the efficacy of gut colonization with MA on lowering plasma TMAO concentrations. Initially, we screened for the colonization potential and TMAO lowering efficacy of five MA species in C57BL/6 mice fed with high choline/TMA supplemented diet, and found out that all five species could colonize and lover plasma TMAO levels, although with different efficacies. The top performing MA, Methanobrevibacter smithii, Methanosarcina mazei, and Methanomicrococcus blatticola, were transplanted into Apoe[-/-] mice fed with high choline/TMA supplemented diet. Similar to C57BL/6 mice, following initial provision of the MA, there was progressive attrition of MA within fecal microbial communities post-transplantation during the initial 3 weeks of the study. In general, plasma TMAO concentrations decreased significantly in proportion to the level of MA colonization. In a subsequent experiment, use of antibiotics and repeated transplantation of Apoe[-/-] mice with M. smithii, led to high engraftment levels during the 9 weeks of the study, resulting in a sustained and significantly lower average plasma TMAO concentrations (18.2 ± 19.6 μM) compared to that in mock-transplanted control mice (120.8 ± 13.0 μM, p < 0.001). Compared to control Apoe[-/-] mice, M. smithii-colonized mice also had a 44% decrease in aortic plaque area (8,570 μm [95% CI 19587-151821] vs. 15,369 μm [95% CI [70058-237321], p = 0.34), and 52% reduction in the fat content in the atherosclerotic plaques (14,283 μm [95% CI 4,957-23,608] vs. 29,870 μm [95% CI 18,074-41,666], p = 0.10), although these differences did not reach significance. Gut colonization with M. smithii leads to a significant reduction in plasma TMAO levels, with a tendency for attenuation of atherosclerosis burden in Apoe[-/-] mice. The anti-atherogenic potential of MA should be further tested in adequately powered experiments.}, }
@article {pmid30283047, year = {2019}, author = {Warner, BB}, title = {The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders.}, journal = {Pediatric research}, volume = {85}, number = {2}, pages = {216-224}, pmid = {30283047}, issn = {1530-0447}, mesh = {Animals ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Mental Disorders/*microbiology ; Mice ; Nervous System Diseases/*microbiology ; }, abstract = {Bidirectional communication between the gut and brain is well recognized, with data now accruing for a specific role of the gut microbiota in that link, referred to as the microbiome-gut-brain axis. This review will discuss the emerging role of the gut microbiota in brain development and behavior. Animal studies have clearly demonstrated effects of the gut microbiota on gene expression and neurochemical metabolism impacting behavior and performance. Based on these changes, a modulating role of the gut microbiota has been demonstrated for a variety of neuropsychiatric disorders, including depression, anxiety, and movement including Parkinson's, and importantly for the pediatric population autism. Critical developmental windows that influence early behavioral outcomes have been identified that include both the prenatal environment and early postnatal colonization periods. The clearest data regarding the role of the gut microbiota on neurodevelopment and psychiatric disorders is from animal studies; however, human data have begun to emerge, including an association between early colonization patterns and cognition. The importance of understanding the contribution of the gut microbiota to the development and functioning of the nervous system lies in the potential to intervene using novel microbial-based approaches to treating neurologic conditions. While pathways of communication between the gut and brain are well established, the gut microbiome is a new component of this axis. The way in which organisms that live in the gut influence the central nervous system (CNS) and host behavior is likely to be multifactorial in origin. This includes immunologic, endocrine, and metabolic mechanisms, all of which are pathways used for other microbial-host interactions. Germ-free (GF) mice are an important model system for understanding the impact of gut microbes on development and function of the nervous system. Alternative animal model systems have further clarified the role of the gut microbiota, including antibiotic treatment, fecal transplantation, and selective gut colonization with specific microbial organisms. Recently, researchers have started to examine the human host as well. This review will examine the components of the CNS potentially influenced by the gut microbiota, and the mechanisms mediating these effects. Links between gut microbial colonization patterns and host behavior relevant to a pediatric population will be examined, highlighting important developmental windows in utero or early in development.}, }
@article {pmid30282817, year = {2018}, author = {Bromberg, JS and Hittle, L and Xiong, Y and Saxena, V and Smyth, EM and Li, L and Zhang, T and Wagner, C and Fricke, WF and Simon, T and Brinkman, CC and Mongodin, EF}, title = {Gut microbiota-dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes.}, journal = {JCI insight}, volume = {3}, number = {19}, pages = {}, pmid = {30282817}, issn = {2379-3708}, support = {R01 AI114496/AI/NIAID NIH HHS/United States ; R01 HL148672/HL/NHLBI NIH HHS/United States ; R37 AI062765/AI/NIAID NIH HHS/United States ; }, mesh = {Allografts/immunology/pathology ; Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Cell Line, Tumor ; Colitis/immunology ; Cytokines/immunology/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/drug effects/*immunology ; Graft Rejection/*immunology/pathology/prevention &amp; control ; Graft Survival/drug effects/immunology ; Heart Transplantation/*adverse effects ; Humans ; *Immunity, Innate ; Immunosuppressive Agents/administration &amp; dosage ; Lymph Nodes/*immunology ; Mice ; Myocardium/pathology ; Pregnancy ; RAW 264.7 Cells ; Tacrolimus/administration &amp; dosage ; Treatment Outcome ; }, abstract = {We hypothesized that the gut microbiota influences survival of murine cardiac allografts through modulation of immunity. Antibiotic pretreated mice received vascularized cardiac allografts and fecal microbiota transfer (FMT), along with tacrolimus immunosuppression. FMT source samples were from normal, pregnant (immune suppressed), or spontaneously colitic (inflammation) mice. Bifidobacterium pseudolongum (B. pseudolongum) in pregnant FMT recipients was associated with prolonged allograft survival and lower inflammation and fibrosis, while normal or colitic FMT resulted in inferior survival and worse histology. Transfer of B. pseudolongum alone resulted in reduced inflammation and fibrosis. Stimulation of DC and macrophage lines with B. pseudolongum induced the antiinflammatory cytokine IL-10 and homeostatic chemokine CCL19 but induced lesser amounts of the proinflammatory cytokines TNFα and IL-6. In contrast, LPS and Desulfovibrio desulfuricans (D. desulfuricans), more abundant in colitic FMT, induced a more inflammatory cytokine response. Analysis of mesenteric and peripheral lymph node structure showed that B. pseudolongum gavage resulted in a higher laminin α4/α5 ratio in the lymph node cortical ridge, indicative of a suppressive environment, while D. desulfuricans resulted in a lower laminin α4/α5 ratio, supportive of inflammation. Discrete gut bacterial species alter immunity and may predict graft outcomes through stimulation of myeloid cells and shifts in lymph node structure and permissiveness.}, }
@article {pmid30281082, year = {2019}, author = {Revolinski, SL and Munoz-Price, LS}, title = {Clostridium difficile in Immunocompromised Hosts: A Review of Epidemiology, Risk Factors, Treatment, and Prevention.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {68}, number = {12}, pages = {2144-2153}, doi = {10.1093/cid/ciy845}, pmid = {30281082}, issn = {1537-6591}, mesh = {*Clostridioides difficile ; Clostridium Infections/*epidemiology/*etiology/prevention &amp; control/therapy ; Coinfection ; Disease Management ; Fecal Microbiota Transplantation/methods ; HIV Infections/complications/epidemiology ; Humans ; *Immunocompromised Host ; Organ Transplantation/adverse effects ; Population Surveillance ; Recurrence ; Risk Assessment ; Risk Factors ; Transplant Recipients ; }, abstract = {Clostridium difficile is a significant pathogen in healthcare today, impacting both hospitalized and community-based patients. Immunocompromised patients experience a high incidence of C. difficile infection, ranging from 6% to 33% in the hematology-oncology population and up to 23% among lung transplant recipients, and have a rate of 7.1-8.3 cases per 1000 patient-years in patients with human immunodeficiency virus (HIV). Recurrence of C. difficile infections among immunocompromised patients is also high, with rates up to 40% in both the hematology-oncology population and solid organ transplant recipients. This higher incidence of C. difficile infection and recurrence is believed to be secondary to frequent antimicrobial use, suppressed immune function, increased exposure to healthcare settings, and higher prevalence of C. difficile colonization. This review summarizes published data describing the epidemiology, risk factors for acquisition and infection, treatment, and prevention of C. difficile in hematology-oncology, solid organ transplant, and HIV-infected patients.}, }
@article {pmid30280023, year = {2018}, author = {Li, X and Li, Z and Chang, Y and Hou, F and Huang, Z and Ni, H and Yang, R and Bi, Y}, title = {Successful transplantation of guinea pig gut microbiota in mice and its effect on pneumonic plague sensitivity.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e5637}, pmid = {30280023}, issn = {2167-8359}, abstract = {Microbiota-driven variations in the inflammatory response are predicted to regulate host responses to infection. Increasing evidence indicates that the gastrointestinal and respiratory tracts have an intimate relationship with each other. Gut microbiota can influence lung immunity whereby gut-derived injurious factors can reach the lungs and systemic circulation via the intestinal lymphatics. The intestinal microbiota's ability to resist colonization can be extended to systemic infections or to pathogens infecting distant sites such as the lungs. Unlike the situation with large mammals, the microtus Yersinia pestis 201 strain exhibits strong virulence in mice, but nearly no virulence to large mammals (such as guinea pigs). Hence, to assess whether the intestinal microbiota from guinea pigs was able to affect the sensitivity of mice to challenge infection with the Y. pestis 201 strain, we fed mice with guinea pig diets for two months, after which they were administered 0.5 ml of guinea pig fecal suspension for 30 days by oral gavage. The stools from each mouse were collected on days 0, 15, and 30, DNA was extracted from them, and 16S rRNA sequencing was performed to assess the diversity and composition of the gut microbiota. We found that the intestinal microbiota transplants from the guinea pigs were able to colonize the mouse intestines. The mice were then infected with Yersinia pestis 201 by lung invasion, but no statistical difference was found in the survival rates of the mice that were colonized with the guinea pig's gut microbiota and the control mice. This indicates that the intestinal microbiota transplantation from the guinea pigs did not affect the sensitivity of the mice to pneumonic plague.}, }
@article {pmid30278075, year = {2018}, author = {Bottino, FO and Gardinali, NR and Salvador, SBS and Figueiredo, AS and Cysne, LB and Francisco, JS and de Oliveira, JM and Machado, MP and Pinto, MA}, title = {Cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with hepatitis E virus: The bone marrow as a possible new viral target.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0205039}, pmid = {30278075}, issn = {1932-6203}, mesh = {Animals ; Bone Marrow/*virology ; Breeding ; Female ; Hepatitis E virus/immunology/*physiology ; Macaca fascicularis/immunology/*virology ; Male ; Seroconversion ; }, abstract = {Hepatitis E virus (HEV) transmission through infected blood and blood products has already been described. However, little is known about the bone marrow (BM) as source of HEV infection. Our study aimed to investigate the presence of HEV antigen (Ag) and histological changes in BM of cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with HEV. Four cynomolgus monkeys with acute, and two with chronic hepatitis E ─ after immunosuppressive therapy with tacrolimus ─ were compared with one colony-bred animal naturally infected. Both, natural and experimental infections were characterized by anti-HEV IgG seroconversion detected by ELISA, and viral RNA isolation confirmed by RT-qPCR and qualitative nested RT-PCR. BM biopsies were collected from all animals, submitted to histology and indirect immunofluorescence techniques and observed, respectively, by light and confocal microscopy. The HEV Ag-fluorescent-labeled cells were detected from BM biopsies obtained from three monkeys with acute and one with chronic hepatitis E, and also from the naturally infected monkey. In the experimentally infected animals with acute hepatitis, HEV Ag detection occurred at 160 days post-infection, even after viral clearance in serum, feces, and liver. Double-stranded RNA, a replicative marker, was detected in BM cells from both acute and chronically infected animals. Major histological findings included vacuolization in mononuclear and endosteal cells, an absence of organized inflammatory infiltrates, and also some fields suggesting displasic focal BM disease. These findings support the hypothesis of BM cells as secondary target sites of HEV persistence. Further experimental studies should be carried out to confirm the assumption of HEV transmission through BM transplantation.}, }
@article {pmid30271330, year = {2018}, author = {Liang, S and Wu, X and Jin, F}, title = {Gut-Brain Psychology: Rethinking Psychology From the Microbiota-Gut-Brain Axis.}, journal = {Frontiers in integrative neuroscience}, volume = {12}, number = {}, pages = {33}, pmid = {30271330}, issn = {1662-5145}, abstract = {Mental disorders and neurological diseases are becoming a rapidly increasing medical burden. Although extensive studies have been conducted, the progress in developing effective therapies for these diseases has still been slow. The current dilemma reminds us that the human being is a superorganism. Only when we take the human self and its partner microbiota into consideration at the same time, can we better understand these diseases. Over the last few centuries, the partner microbiota has experienced tremendous change, much more than human genes, because of the modern transformations in diet, lifestyle, medical care, and so on, parallel to the modern epidemiological transition. Existing research indicates that gut microbiota plays an important role in this transition. According to gut-brain psychology, the gut microbiota is a crucial part of the gut-brain network, and it communicates with the brain via the microbiota-gut-brain axis. The gut microbiota almost develops synchronously with the gut-brain, brain, and mind. The gut microbiota influences various normal mental processes and mental phenomena, and is involved in the pathophysiology of numerous mental and neurological diseases. Targeting the microbiota in therapy for these diseases is a promising approach that is supported by three theories: the gut microbiota hypothesis, the "old friend" hypothesis, and the leaky gut theory. The effects of gut microbiota on the brain and behavior are fulfilled by the microbiota-gut-brain axis, which is mainly composed of the nervous pathway, endocrine pathway, and immune pathway. Undoubtedly, gut-brain psychology will bring great enhancement to psychology, neuroscience, and psychiatry. Various microbiota-improving methods including fecal microbiota transplantation, probiotics, prebiotics, a healthy diet, and healthy lifestyle have shown the capability to promote the function of the gut-brain, microbiota-gut-brain axis, and brain. It will be possible to harness the gut microbiota to improve brain and mental health and prevent and treat related diseases in the future.}, }
@article {pmid30268564, year = {2019}, author = {Krajicek, E and Fischer, M and Allegretti, JR and Kelly, CR}, title = {Nuts and Bolts of Fecal Microbiota Transplantation.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {2}, pages = {345-352}, doi = {10.1016/j.cgh.2018.09.029}, pmid = {30268564}, issn = {1542-7714}, mesh = {Clostridium Infections/prevention &amp; control/*therapy ; Cross Infection/prevention &amp; control/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Secondary Prevention/methods ; Treatment Outcome ; United States ; }, abstract = {Clostridium difficile infection (CDI) has become the leading cause of nosocomial infection in the United States with significant risk of both morbidity and mortality. While antimicrobial therapy forms the basis of treatment, there are several clinical scenarios in which antimicrobial therapy alone is insufficient. Evidence continues to show the safety and efficacy fecal microbiota transplantation (FMT) in recurrent and severe CDI. This review will outline FMT efficacy, safety, and indications and present practical advice for clinicians interested in best practices around delivery of FMT.}, }
@article {pmid30268000, year = {2018}, author = {Pietsch, C and Ennuschat, N and Härtel, S and Liebert, UG}, title = {Within-host evolution of virus variants during chronic infection with novel GII.P26-GII.26 norovirus.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {108}, number = {}, pages = {96-102}, doi = {10.1016/j.jcv.2018.09.013}, pmid = {30268000}, issn = {1873-5967}, mesh = {Caliciviridae Infections/*virology ; Capsid Proteins/genetics ; Chronic Disease ; *Evolution, Molecular ; Feces/virology ; Gastroenteritis/virology ; *Genetic Variation ; Genome, Viral ; Genotype ; High-Throughput Nucleotide Sequencing ; Host Microbial Interactions/*genetics ; Humans ; Immunocompromised Host ; Norovirus/*genetics/isolation &amp; purification ; Phenotype ; Quasispecies/genetics ; RNA, Viral/genetics ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Noroviruses are a leading cause of acute gastroenteritis in all age groups. They generally cause a rapidly self-limiting illness. However, chronic norovirus diarrheal disease occurs in immunocompromised individuals, and is accompanied by persistent shedding of infectious norovirus in stool.<br><br>OBJECTIVES: The study aims to characterize a novel GII.P26-GII.26 norovirus strain. Furthermore, it analyses viral mutations arising during chronic infection of an immunocompromised host.<br><br>STUDY DESIGN: Over the course of more than three years, stool samples were obtained from an immunocompromised patient and screened for the presence of norovirus RNA by real-time PCR and norovirus antigen by immunoassay. Viral population kinetics was analyzed by conventional and high-throughput-sequencing.<br><br>RESULTS: Real-time PCR yielded high amounts of norovirus RNA in the stool, but antigen immunoassays failed to detect the virus. The near complete norovirus genome was assigned as novel GII.P26-GII.26 genotype. Conventional as well as high-throughput sequencing pointed to a heterogeneous viral population with low rates of non-synonymous substitutions. Within-host evolution was enhanced in non-structural protein p22 and the N-terminal arm of the capsid protein VP1 but reduced in the viral polymerase RdRp. Intermittent non-synonymous substitutions in the protruding domain of the VP1 reverted fully over time.<br><br>CONCLUSIONS: Confirmation of novel GII.P26-GII.26 norovirus genotypes provides insight into norovirus genetic diversity. The study further illustrates norovirus infection as an important differential diagnosis of recurrent persistent diarrhea in immunocompromised patients. The provided data on within-host evolution contribute to the insight of the mechanisms of viral persistence and pathogenesis in chronic norovirus infections.}, }
@article {pmid30267651, year = {2019}, author = {De Ligny, WR and Kerkhof, MH and Ruiz-Zapata, AM}, title = {Regenerative medicine as a therapeutic option for fecal incontinence: a systematic review of preclinical and clinical studies.}, journal = {American journal of obstetrics and gynecology}, volume = {220}, number = {2}, pages = {142-154.e2}, doi = {10.1016/j.ajog.2018.09.009}, pmid = {30267651}, issn = {1097-6868}, mesh = {Fecal Incontinence/*therapy ; *Guided Tissue Regeneration ; Humans ; Regenerative Medicine ; *Stem Cell Transplantation ; *Tissue Engineering ; Translational Research, Biomedical ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal incontinence is the uncontrollable loss of stool and has a prevalence of around 7-15%. This condition has serious implications for patients' quality of life. Current treatment options show unsatisfactory results. A novel treatment option is therefore needed.<br><br>OBJECTIVE: This systematic review aims to perform a quality assessment and to give a critical overview of the current research available on regenerative medicine as a treatment for fecal incontinence.<br><br>STUDY DESIGN: A systematic search strategy was applied in PubMed, Cochrane Library, EMBASE, MEDLINE, Web of Science, and Cinahl from inception until March of 2018. Studies were found relevant when the animals or patients in the studied group had objectively determined or induced fecal incontinence, and the intervention must have used any kind of cells, stem cells, or biocompatible material, with or without the use of trophic factors. Studies were screened on title and consecutively on abstract for relevance by 2 independent investigators. The risk of bias of preclinical studies was assessed using the SYstematic Review Centre for Laboratory animal Experimentation risk of bias tool for animal studies, and for clinical studies the Cochrane risk of bias tool for randomized trials was used.<br><br>RESULTS: In all, 34 preclinical studies and 5 clinical studies were included. Animal species, type of anal sphincter injury, intervention, and outcome parameters were heterogenous. Therefore, a meta-analysis could not be performed. The overall risk of bias of the included studies was high.<br><br>CONCLUSION: The efficacy of regenerative medicine to treat fecal incontinence could not be determined due to the high risk of bias and heterogenicity of the available preclinical and clinical studies. The findings of this systematic review may result in improved study design of future studies, which could help the translation of regenerative medicine to the clinic as an alternative to current treatments for fecal incontinence.}, }
@article {pmid30265170, year = {2018}, author = {Martinez, C and Edwards, J and Hassoun, A}, title = {Commercialized fecal microbiota transplantation provides efficacious treatment of Clostridium difficile infection.}, journal = {Infectious diseases (London, England)}, volume = {50}, number = {11-12}, pages = {864-867}, doi = {10.1080/23744235.2018.1500709}, pmid = {30265170}, issn = {2374-4243}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*physiology ; Clostridium Infections/microbiology/*therapy ; Cohort Studies ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Self Report ; Treatment Outcome ; }, }
@article {pmid30263058, year = {2018}, author = {Maleki Vareki, S and Chanyi, RM and Abdur-Rashid, K and Brennan, L and Burton, JP}, title = {Moving on from Metchnikoff: thinking about microbiome therapeutics in cancer.}, journal = {Ecancermedicalscience}, volume = {12}, number = {}, pages = {867}, pmid = {30263058}, issn = {1754-6605}, abstract = {Precision medicine now needs to also consider the microbiome in oncology treatment. Ingested substances, whether they are a carcinogenic or therapeutic agent, will likely come into contact with the microbiota. Even those delivered extra-intestinally can be influenced beyond xenobiotic metabolism by biochemical factors associated with the microbiota or by an immunological predisposition created by the microbiome. We need to undertake one of the largest paradigm shifts to ever occur in medicine, that is, every drug or ingested substance needs to be re-evaluated for its pharmacological effect post-microbiome interaction. The importance of the microbiome with a focus on the treatment of cancer is discussed. In the near future, it may be possible to specifically manipulate the microbial composition within cancer patients to improve the therapeutic potential of existing oncological agents. However, the current tools to do so are limited. Targeted modulation is likely to be achieved by addition, selective enhancement or depletion of specific microbial types. This may include compounds such as narrow spectrum antimicrobial agents or oligosaccharides that will kill or enhance the bacterial growth of distinct members of the microbiota, respectively. This will stimulate a new era in these fields.}, }
@article {pmid30257956, year = {2018}, author = {Taur, Y and Coyte, K and Schluter, J and Robilotti, E and Figueroa, C and Gjonbalaj, M and Littmann, ER and Ling, L and Miller, L and Gyaltshen, Y and Fontana, E and Morjaria, S and Gyurkocza, B and Perales, MA and Castro-Malaspina, H and Tamari, R and Ponce, D and Koehne, G and Barker, J and Jakubowski, A and Papadopoulos, E and Dahi, P and Sauter, C and Shaffer, B and Young, JW and Peled, J and Meagher, RC and Jenq, RR and van den Brink, MRM and Giralt, SA and Pamer, EG and Xavier, JB}, title = {Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant.}, journal = {Science translational medicine}, volume = {10}, number = {460}, pages = {}, pmid = {30257956}, issn = {1946-6242}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Biodiversity ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Hematopoietic Stem Cell Transplantation ; Humans ; Longitudinal Studies ; Transplantation, Autologous ; }, abstract = {Antibiotic treatment can deplete the commensal bacteria of a patient's gut microbiota and, paradoxically, increase their risk of subsequent infections. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), antibiotic administration is essential for optimal clinical outcomes but significantly disrupts intestinal microbiota diversity, leading to loss of many beneficial microbes. Although gut microbiota diversity loss during allo-HSCT is associated with increased mortality, approaches to reestablish depleted commensal bacteria have yet to be developed. We have initiated a randomized, controlled clinical trial of autologous fecal microbiota transplantation (auto-FMT) versus no intervention and have analyzed the intestinal microbiota profiles of 25 allo-HSCT patients (14 who received auto-FMT treatment and 11 control patients who did not). Changes in gut microbiota diversity and composition revealed that the auto-FMT intervention boosted microbial diversity and reestablished the intestinal microbiota composition that the patient had before antibiotic treatment and allo-HSCT. These results demonstrate the potential for fecal sample banking and posttreatment remediation of a patient's gut microbiota after microbiota-depleting antibiotic treatment during allo-HSCT.}, }
@article {pmid30257633, year = {2018}, author = {White, LS and Van den Bogaerde, J and Kamm, M}, title = {The gut microbiota: cause and cure of gut diseases.}, journal = {The Medical journal of Australia}, volume = {209}, number = {7}, pages = {312-317}, doi = {10.5694/mja17.01067}, pmid = {30257633}, issn = {1326-5377}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; *Gastrointestinal Diseases/microbiology/physiopathology/therapy ; *Gastrointestinal Microbiome/drug effects/genetics/physiology ; Humans ; Inflammatory Bowel Diseases/microbiology/physiopathology/therapy ; Liver Diseases/microbiology/physiopathology/therapy ; Metabolic Syndrome/microbiology/physiopathology/therapy ; Metagenomics ; Mice ; *Obesity/microbiology/physiopathology/therapy ; }, abstract = {The gastrointestinal microbiota is emerging as a central factor in the pathogenesis of a range of gastrointestinal and hepatic disorders. Epidemiological studies, and experimental studies in animals and humans, have highlighted a likely causative role of this microbial community in the modern global epidemics of inflammatory bowel disease, non-alcoholic fatty liver disease, non-alcoholic steato-hepatitis, obesity and metabolic syndrome. New techniques for microbial culture and gene sequencing are enabling the identification of specific pathogens and protective organisms in these conditions. Factors that change the microbiota are being defined: dietary pattern, specific foods, food additives in processed food and drinks, such as emulsifiers and non-sugar sweeteners, and antibiotics. Microbiota changes in early life appear critical to the later development of a range of inflammatory disorders. For many of these conditions, the treatment paradigm will change, at least in part, from immune suppression and drug therapy to treatments that reshape the microbiota or restore its integrity. These treatments include dietary changes, specific microbial manipulation and faecal microbiota transplantation. A dialogue is needed regarding population strategies that target disease prevention. This will include how food is produced, what additives it contains, and how it is processed. Widespread use of antibiotics, from agricultural and veterinary to medicinal settings, needs more attention. At the individual level, microbial profiles may be able to predict who is at risk of disease when subjected to particular environmental influences, and what microbial restoration is needed to minimise risk.}, }
@article {pmid30251184, year = {2018}, author = {Hughes, HK and Rose, D and Ashwood, P}, title = {The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders.}, journal = {Current neurology and neuroscience reports}, volume = {18}, number = {11}, pages = {81}, pmid = {30251184}, issn = {1534-6293}, support = {P01 ES011269/ES/NIEHS NIH HHS/United States ; R01 HD090214/HD/NICHD NIH HHS/United States ; R01 ES015359/ES/NIEHS NIH HHS/United States ; U54 HD079125/HD/NICHD NIH HHS/United States ; R21 HD086669/HD/NICHD NIH HHS/United States ; R21 ES025560/ES/NIEHS NIH HHS/United States ; UL1 RR024146/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Autism Spectrum Disorder/complications/diagnosis/*metabolism ; Brain/*metabolism ; Dysbiosis/complications/diagnosis/*metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Metabolomics/methods/trends ; Microbiota/*physiology ; }, abstract = {PURPOSE OF REVIEW: There is a growing body of evidence indicating the gut microbiota influence neurodevelopment and behavior. The purposes of this review are to provide an overview of studies analyzing the microbiota and their metabolites in autism spectrum disorders (ASD) and to discuss the possible mechanisms of action involved in microbial influence on the brain and behavior.<br><br>RECENT FINDINGS: The microbiota-gut-brain (MGB) axis has been extensively studied in animal models, and it is clear that alterations in the composition of microbiota alter neurological and behavioral outcomes. However, findings in human studies are less abundant. Although there are several studies so far showing altered microbiota (dysbiosis) in ASD, the results are heterogeneous and often contradictory. Intervention studies such as fecal microbiota transplant therapies show promise and lend credence to the involvement of the microbiota in ASD. A role for the microbiota in ASD is likely; however, further studies elucidating microbial or metabolomic signatures and mechanisms of action are needed. Future research should focus on intervention studies that can identify specific metabolites and immune mediators that improve with treatment to help identify etiologies and pathological mechanisms of ASD.}, }
@article {pmid30250472, year = {2018}, author = {Haak, BW and Prescott, HC and Wiersinga, WJ}, title = {Therapeutic Potential of the Gut Microbiota in the Prevention and Treatment of Sepsis.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2042}, pmid = {30250472}, issn = {1664-3224}, support = {K08 GM115859/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Disease Susceptibility ; Dysbiosis/microbiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Prebiotics ; Probiotics/*therapeutic use ; Sepsis/microbiology/*therapy ; }, abstract = {Alongside advances in understanding the pathophysiology of sepsis, there have been tremendous strides in understanding the pervasive role of the gut microbiota in systemic host resistance. In pre-clinical models, a diverse and balanced gut microbiota enhances host immunity to both enteric and systemic pathogens. Disturbance of this balance increases susceptibility to sepsis and sepsis-related organ dysfunction, while restoration of the gut microbiome is protective. Patients with sepsis have a profoundly distorted composition of the intestinal microbiota, but the impact and therapeutic potential of the microbiome is not well-established in human sepsis. Modulation of the microbiota consists of either resupplying the pool of beneficial microbes by administration of probiotics, improving the intestinal microenvironment to enhance the growth of beneficial species by dietary interventions and prebiotics, or by totally recolonizing the gut with a fecal microbiota transplantation (FMT). We propose that there are three potential opportunities to utilize these treatment modalities over the course of sepsis: to decrease sepsis incidence, to improve sepsis outcome, and to decrease late mortality after sepsis. Exploring these three avenues will provide insight into how disturbances of the microbiota can predispose to, or even perpetuate the dysregulated immune response associated with this syndrome, which in turn could be associated with improved sepsis management.}, }
@article {pmid30249750, year = {2018}, author = {Lee, KW and Kim, M and Lee, CH}, title = {Treatment of Dextran Sulfate Sodium-Induced Colitis with Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Inhibitor MI-2 Is Associated with Restoration of Gut Immune Function and the Microbiota.}, journal = {Infection and immunity}, volume = {86}, number = {12}, pages = {}, pmid = {30249750}, issn = {1098-5522}, mesh = {Acetanilides/*pharmacology ; Animals ; Cells, Cultured ; Colitis/chemically induced/*immunology/microbiology/*therapy ; Cytokines/immunology ; Dextran Sulfate ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Inflammation ; Intestines/drug effects/*immunology/microbiology ; Macrophages ; Mice ; Mice, Inbred C57BL ; Monocytes ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein/*antagonists &amp; inhibitors/immunology ; Triazoles/*pharmacology ; }, abstract = {Disruption of the healthy intestinal microbiome and homeostasis of the intestinal immune system, which are closely interactive, are two key factors for ulcerative colitis. Here, we show that MI-2, a selective inhibitor of mucosa-associated lymphoid tissue lymphoma translocation-1 (MALT1), alleviated excessive inflammatory responses and was associated with restoration of healthy intestinal microbiome in mice suffering from dextran sulfate sodium (DSS)-induced colitis. We found that the diversity of intestinal microbiome of mice with DSS-induced colitis was significantly lower than that of healthy mice. However, MI-2 treatment in mice with DSS-induced colitis resulted in restored microbially diverse populations. To understand the possibility of the beneficial effect of the restored microbially diverse populations of MI-2-treated mice with DSS-induced colitis, we showed that inserting fecal microbiota from MI-2-treated mice with DSS-induced colitis and healthy control mice into mice with DSS-induced colitis could alleviate symptoms of colitis. The possibility of MI-2 treatment in DSS-induced colitis, associated with restoration of healthy microbially diverse populations in addition to reshaping host immune modulating capacity by reducing inflammatory cytokines (tumor necrosis factor alpha, interleukin-1β [IL-1β], IL-17α, and IL-22), may be considered therapeutic for ulcerative colitis.}, }
@article {pmid30249647, year = {2018}, author = {Plantamura, E and Dzutsev, A and Chamaillard, M and Djebali, S and Moudombi, L and Boucinha, L and Grau, M and Macari, C and Bauché, D and Dumitrescu, O and Rasigade, JP and Lippens, S and Plateroti, M and Kress, E and Cesaro, A and Bondu, C and Rothermel, U and Heikenwälder, M and Lina, G and Bentaher-Belaaouaj, A and Marie, JC and Caux, C and Trinchieri, G and Marvel, J and Michallet, MC}, title = {MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic phenotype.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10404-10409}, pmid = {30249647}, issn = {1091-6490}, mesh = {Adaptor Proteins, Signal Transducing/*physiology ; Animals ; Disease Models, Animal ; Dysbiosis/*complications ; Female ; Gastrointestinal Microbiome/*immunology ; Homeodomain Proteins/genetics/metabolism ; Hypersensitivity/*etiology/metabolism/pathology ; Intestines/*immunology/microbiology/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; Signal Transduction ; Skin Diseases, Bacterial/*etiology/metabolism/pathology ; }, abstract = {Prominent changes in the gut microbiota (referred to as "dysbiosis") play a key role in the development of allergic disorders, but the underlying mechanisms remain unknown. Study of the delayed-type hypersensitivity (DTH) response in mice contributed to our knowledge of the pathophysiology of human allergic contact dermatitis. Here we report a negative regulatory role of the RIG-I-like receptor adaptor mitochondrial antiviral signaling (MAVS) on DTH by modulating gut bacterial ecology. Cohousing and fecal transplantation experiments revealed that the dysbiotic microbiota of Mavs[-/-] mice conferred a proallergic phenotype that is communicable to wild-type mice. DTH sensitization coincided with increased intestinal permeability and bacterial translocation within lymphoid organs that enhanced DTH severity. Collectively, we unveiled an unexpected impact of RIG-I-like signaling on the gut microbiota with consequences on allergic skin disease outcome. Primarily, these data indicate that manipulating the gut microbiota may help in the development of therapeutic strategies for the treatment of human allergic skin pathologies.}, }
@article {pmid30249225, year = {2018}, author = {Tian, Y and Liu, T and Zhao, CQ and Lei, ZY and Fan, DL and Mao, TC}, title = {Negative pressure wound therapy and split thickness skin graft aided in the healing of extensive perineum necrotizing fasciitis without faecal diversion: a case report.}, journal = {BMC surgery}, volume = {18}, number = {1}, pages = {77}, pmid = {30249225}, issn = {1471-2482}, mesh = {Fasciitis, Necrotizing/pathology/*therapy ; Humans ; Male ; Middle Aged ; *Negative-Pressure Wound Therapy ; *Perineum ; Pseudomonas Infections/pathology/*therapy ; *Pseudomonas aeruginosa ; *Skin Transplantation ; Surgical Flaps ; Wound Healing ; }, abstract = {BACKGROUND: Perineum necrotizing fasciitis, also known as Fournier gangrene (FG), is a rare but highly mortal infectious necrotizing fasciitis with or without involvement of the underlying muscle. Evidence exists that negative pressure wound therapy (NPWT) combined with a split thickness skin graft (STSG) can help to heal wounds with FG. However, when the wound spreads to the anal area, it can easily be contaminated by faeces, causing a more extensive wounds; thus, faecal diversion is considered. Here, we report a case of extensive perineum necrotizing fasciitis that spread to near the anus; NPWT combined with STSGs was used to help heal the wound without faecal diversion.<br><br>CASE PRESENTATION: A 47-year-old male patient was admitted with extensive perineum fascia necrosis caused by Pseudomonas aeruginosa that rapidly spread to near the anus. After comprehensive therapy completed wound bed preparation, STSGs from the scalp were grafted to the wound, and NPWT was applied to improve STSGs survival and seal the anus without faecal diversion. After treatment, graft take was 95%, and the exposed testicular and residual wounds were repaired with a local skin flap. At discharge, the wound had decreased to two pea-sized areas. The patient received conventional moist gauze therapy to close the residual wound at the local hospital. A follow-up by telephone 1&#xa0;month later showed that both wounds had healed and that the patient was satisfied with the outcome.<br><br>CONCLUSION: NPWT use combined with STSGs to cover the whole wound and the anus without faecal diversion is a safe and effective method to help with wound healing and avoid contamination with excrement.}, }
@article {pmid30246002, year = {2018}, author = {Shogbesan, O and Poudel, DR and Victor, S and Jehangir, A and Fadahunsi, O and Shogbesan, G and Donato, A}, title = {A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplant for Clostridium difficile Infection in Immunocompromised Patients.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {2018}, number = {}, pages = {1394379}, pmid = {30246002}, issn = {2291-2797}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/microbiology/*therapy ; Colonoscopy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Humans ; *Immunocompromised Host ; *Microbiota ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent Clostridium difficile (CD) infection, with resolution in 80% to 90% of patients. However, immunosuppressed patients were often excluded from FMT trials, so safety and efficacy in this population are unknown.<br><br>METHODS: We searched MEDLINE and EMBASE for English language articles published on FMT for treatment of CD infection in immunocompromised patients (including patients on immunosuppressant medications, patients with human immunodeficiency virus (HIV), inherited or primary immunodeficiency syndromes, cancer undergoing chemotherapy, or organ transplant, including-bone marrow transplant) of all ages. We excluded inflammatory bowel disease patients that were not on immunosuppressant medications. Resolution and adverse event rates (including secondary infection, rehospitalization, and death) were calculated.<br><br>RESULTS: Forty-four studies were included, none of which were randomized designs. A total of 303 immunocompromised patients were studied. Mean patient age was 57.3 years. Immunosuppressant medication use was the reason for the immunocompromised state in the majority (77.2%), and 19.2% had greater than one immunocompromising condition. Seventy-six percent were given FMT via colonoscopy. Of the 234 patients with reported follow-up outcomes, 207/234 (87%) reported resolution after first treatment, with 93% noting success after multiple treatments. There were 2 reported deaths, 2 colectomies, 5 treatment-related infections, and 10 subsequent hospitalizations.<br><br>CONCLUSION: We found evidence that supports the use of FMT for treatment of CD infection in immunocompromised patients, with similar rates of serious adverse events to immunocompetent patients.}, }
@article {pmid30245786, year = {2018}, author = {Mcilroy, JR and Nalagatla, N and Hansen, R and Hart, A and Hold, GL}, title = {Faecal microbiota transplantation as a treatment for inflammatory bowel disease: a national survey of adult and paediatric gastroenterologists in the UK.}, journal = {Frontline gastroenterology}, volume = {9}, number = {4}, pages = {250-255}, pmid = {30245786}, issn = {2041-4137}, abstract = {BACKGROUND: Interest in the use of faecal microbiota transplantation (FMT) in inflammatory bowel disease (IBD) has increased following outcomes in patients with Clostridioides difficile infection (CDI). While research exploring clinician awareness and attitude towards the use of FMT in CDI has been carried out, data for IBD are currently lacking.<br><br>OBJECTIVE: To assess the perceptions of gastroenterologists and current practice relating to FMT as a treatment for IBD in the UK.<br><br>DESIGN: A web-based survey (Snap Survey software) was distributed through the British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition e-newsletters, and at the BSG Conference in June 2017.<br><br>RESULTS: 61 respondents completed the survey including presubspecialty trainees, gastroenterology specialists, associate specialists and consultants. Most (95%; n=58) respondents stated that they had heard of FMT being used as a treatment for IBD prior to participating in the survey. Based on current evidence, 34% (n=21) of respondents would consider using FMT in patients with IBD, 26% (n=16) would not and 39% (n=24) were undecided. When asked to rank routes of delivery in terms of preference, nasogastric tube was the least preferred route (39%; n=24) and oral capsule was the most preferred route (34%; n=21).<br><br>CONCLUSIONS: A clear majority of UK gastroenterologists recognise FMT as a potential treatment for IBD; however, uptake is limited. A proportion of clinicians would consider FMT in IBD and the majority would consider entering patients into clinical trials. Future work should explore the utility and efficacy of oral FMT capsules in IBD.}, }
@article {pmid30244328, year = {2018}, author = {Ramakrishnan, B and Gopalakrishnan, R and Senthur Nambi, P and Durairajan, SK and Madhumitha, R and Tarigopula, A and Chandran, C and Ramasubramanian, V}, title = {Utility of multiplex polymerase chain reaction (PCR) in diarrhea-An Indian perspective.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {37}, number = {5}, pages = {402-409}, pmid = {30244328}, issn = {0975-0711}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Diarrhea/*diagnosis/microbiology ; Feces/*microbiology ; Female ; Humans ; India ; Infant ; Infant, Newborn ; Male ; Microbiological Techniques/*methods ; Middle Aged ; Multiplex Polymerase Chain Reaction/*statistics &amp; numerical data ; Retrospective Studies ; Sensitivity and Specificity ; Young Adult ; }, abstract = {BACKGROUND: Infective diarrhea causes morbidity worldwide. Polymerase chain reaction (PCR)-based pathogen diagnostics of diarrheal stool specimens are shown to be highly sensitive and rapid as opposed to conventional diagnostics.<br><br>METHODS: We analyzed the performance of FilmArray gastrointestinal (GI) panel, one such multiplex PCR test, on stool specimens in patients presenting with diarrhea to our hospital from March 2016 to September 2017 and compared the results with conventional diagnostic tests.<br><br>RESULTS: A total of 106 patients were included. The panel detected at least one target in 54 out of 106 patients (50.9%) with results available on the same day. Multiple targets were detected in 26 out of 54 patients who tested positive (48.1%). Bacteria as an isolated etiology for diarrhea was present in 34 patients (62.9%), viruses (16.7%, nine patients), parasites (7.4%, four patients), and multiple pathogens in seven patients (12.9%). Enteroaggregative Escherichia coli (EAEC) was the commonest pathogen&#xa0;detected (in 23, 24% patients). Conventional diagnostic investigations, undertaken in&#xa0;68/106 (64.1%) patients were positive in 12 (17.65%) as compared to&#xa0;54/106&#xa0;(50.9%) (p&#x2009;<&#x2009;0.0001). Conventional&#xa0; investigations detected a pathogen not included in the study panel in 11 of 52 patients (21.1%).<br><br>CONCLUSION: FilmArray multiplex PCR panel detects a wide array of GI pathogens including viruses and co-infections at a shorter time with more sensitivity compared to conventional diagnostics. Henceforth, it may&#xa0;facilitate treatment decisions, isolation policy, and antimicrobial stewardship in patients with diarrhea requiring hospitalization.}, }
@article {pmid30241676, year = {2018}, author = {Mullish, BH and Quraishi, MN and Segal, JP and Williams, HRT and Goldenberg, SD}, title = {Introduction to the joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) faecal microbiota transplant guidelines.}, journal = {The Journal of hospital infection}, volume = {100}, number = {2}, pages = {130-132}, doi = {10.1016/j.jhin.2018.07.028}, pmid = {30241676}, issn = {1532-2939}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; *Practice Guidelines as Topic ; }, }
@article {pmid30240668, year = {2019}, author = {Härter, B and Scholl-Bürgi, S}, title = {Abdominal Pain and Constipation.}, journal = {Gastroenterology}, volume = {156}, number = {3}, pages = {e12-e13}, doi = {10.1053/j.gastro.2018.09.033}, pmid = {30240668}, issn = {1528-0012}, mesh = {Abdominal Pain/diagnosis/etiology ; Bezoars/*complications/diagnostic imaging ; Child ; Constipation/*diagnostic imaging/physiopathology ; Fecal Impaction/complications/diagnostic imaging/*etiology/therapy ; Humans ; Male ; Radiography/methods ; Risk Assessment ; Seeds/*adverse effects ; Severity of Illness Index ; Treatment Outcome ; }, }
@article {pmid30234761, year = {2019}, author = {Singh, HK and Ee, LC}, title = {Recurrent Abdominal Pain in Children: Is Colonoscopy Indicated?.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {68}, number = {2}, pages = {214-217}, doi = {10.1097/MPG.0000000000002155}, pmid = {30234761}, issn = {1536-4801}, mesh = {Abdominal Pain/*diagnosis ; Adolescent ; Child ; Child, Preschool ; Colonoscopy/*statistics &amp; numerical data ; Feces/chemistry ; Female ; Gastrointestinal Hemorrhage/*diagnosis ; Humans ; Leukocyte L1 Antigen Complex/analysis ; Male ; Recurrence ; Retrospective Studies ; }, abstract = {Recurrent abdominal pain (RAP) in children is common, with most functional in origin. Colonoscopy has sometimes been performed to exclude pathology but its role is unclear. Our aim therefore was to assess the diagnostic yield and role of colonoscopy in these children. Retrospective review of consecutive colonoscopies in a tertiary pediatric hospital between November 2011 and October 2015 was undertaken. Only those with RAP as an indication for procedure were included. Chart review of patients with pain was undertaken to ensure they fulfilled Rome IV criteria. Patient demographics, indication for procedure, and adjunct preprocedure tests were noted. Statistical analyses were performed with SPSS software. A total of 652 colonoscopies were performed, of which 68 (10%) had abdominal pain as one of the indications, and was the sole indication in 15 (2%) patients. All 68 patients had preprocedure serum inflammatory markers measured and 53% (36/68) had stool calprotectin. Positive histology was found in 10% (7/68) including Crohn disease (n = 3), polyps (n = 2), and microscopic colitis (n = 2). The remaining 61 patients had normal colonoscopy and ileocolonic biopsies. Of the 36 patients 5 had raised fecal calprotectin, and all had abnormal histology. Serum inflammatory markers were raised in 4 patients and all also had abnormal calprotectin. No patient with isolated abdominal pain had positive histology. Rectal bleeding was the only associated indication to predict abnormal histology (P = 0.019). Colonoscopy is likely not warranted in children with RAP without bleeding, weight loss, or altered bowel habit. Fecal calprotectin is useful in helping predict positive findings.}, }
@article {pmid30233520, year = {2018}, author = {Fortier, LC}, title = {Bacteriophages Contribute to Shaping Clostridioides (Clostridium) difficile Species.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2033}, pmid = {30233520}, issn = {1664-302X}, abstract = {Bacteriophages (phages) are bacterial viruses that parasitize bacteria. They are highly prevalent in nature, with an estimated 10[31] viral particles in the whole biosphere, and they outnumber bacteria by at least 10-fold. Hence, phages represent important drivers of bacterial evolution, although our knowledge of the role played by phages in the mammalian gut is still embryonic. Several pathogens owe their virulence to the integrated phages (prophages) they harbor, which encode diverse virulence factors such as toxins. Clostridioides (Clostridium) difficile is an important opportunistic pathogen and several phages infecting this species have been described over the last decade. However, their exact contribution to the biology and virulence of this pathogen remains elusive. Current data have shown that C. difficile phages can alter virulence-associated phenotypes, in particular toxin production, by interfering with bacterial regulatory circuits through crosstalk with phage proteins for example. One phage has also been found to encode a complete binary toxin locus. Multiple regulatory genes have also been identified in phage genomes, suggesting that their impact on the host can be complex and often subtle. In this minireview, the current state of knowledge, major findings, and pending questions regarding C. difficile phages will be presented. In addition, with the apparent role played by phages in the success of fecal microbiota transplantation and the perspective of phage therapy for treatment of recurrent C. difficile infection, it has become even more crucial to understand what C. difficile phages do in the gut, how they impact their host, and how they influence the epidemiology and evolution of this clinically important pathogen.}, }
@article {pmid30232757, year = {2018}, author = {Lu, M and Wang, Z}, title = {Microbiota and Aging.}, journal = {Advances in experimental medicine and biology}, volume = {1086}, number = {}, pages = {141-156}, doi = {10.1007/978-981-13-1117-8_9}, pmid = {30232757}, issn = {0065-2598}, mesh = {*Aging ; Cardiovascular Diseases/microbiology ; Diabetes Mellitus, Type 2/microbiology ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/microbiology ; Obesity/microbiology ; }, abstract = {The human gut microbiota is a huge ecosystem that provides lots of functions for host development, immune system, and metabolism. Gut microbiota is linked to lots of diseases, including human metabolic diseases such as obesity, type 2 diabetes (T2D), irritable bowel syndrome, and cardiovascular disease (CVD). Few studies, however, have noted the relationship between aging and microbiota; the connection between aging and microbiota remains largely to be researched. In this review, recent research findings are summarized on the role of gut microbiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in antiaging medicine.}, }
@article {pmid30227892, year = {2018}, author = {Staley, C and Kaiser, T and Vaughn, BP and Graiziger, CT and Hamilton, MJ and Rehman, TU and Song, K and Khoruts, A and Sadowsky, MJ}, title = {Predicting recurrence of Clostridium difficile infection following encapsulated fecal microbiota transplantation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {166}, pmid = {30227892}, issn = {2049-2618}, support = {R21 AI114722/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteria/classification/genetics/isolation &amp; purification ; Clostridioides difficile/*physiology ; Clostridium Infections/microbiology/*therapy ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The use of freeze-dried, encapsulated donor material for FMT (cap-FMT) allows for an easy route of administration and remains clinically effective in the majority of rCDI patients. We hypothesized that specific shifts in the microbiota in response to cap-FMT could predict clinical outcome. We further evaluated the degree of donor microbiota engraftment to determine the extent that donor transfer contributed to recovery.<br><br>RESULTS: In total, 89 patients were treated with 100 separate cap-FMTs, with a success rate (no rCDI 60&#xa0;days post cap-FMT) of 80%. Among responders, the lower alpha diversity (ANOVA P&#x2009;<&#x2009;0.05) observed among patient's pre-FMT samples was restored following cap-FMT. At 1&#xa0;week post-FMT, community composition varied by clinical outcome (ANOSIM P&#x2009;<&#x2009;0.001), with similar abundances among families (Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae) in responder and donor samples. Families that showed differential abundances by outcome (response vs. recurrence) from samples collected 7&#xa0;days following cap-FMT were used to construct a regression tree-based model to predict recurrence. Results showed a training accuracy of 100% to predict recurrence and the model was 97% accurate against a test data set of samples collected 8-20&#xa0;days following cap-FMT. Evaluation of the extent of engraftment using the Bayesian algorithm SourceTracker revealed that approximately 50% of the post-FMT communities of responders were attributable to donor microbiota, while an additional 20-30% of the communities were similar to a composite healthy microbiota consisting of all donor samples.<br><br>CONCLUSIONS: Regression tree-based analyses of microbial communities identified taxa significantly related to clinical response after 7&#xa0;days, which can be targeted to improve microbial therapeutics. Furthermore, reinstatement of a healthy assemblage following cap-FMT was only partially attributable to explicit donor engraftment and continued to develop towards an overall healthy assemblage, independent of donor.}, }
@article {pmid30224732, year = {2018}, author = {Jang, HM and Lee, KE and Lee, HJ and Kim, DH}, title = {Immobilization stress-induced Escherichia coli causes anxiety by inducing NF-κB activation through gut microbiota disturbance.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {13897}, pmid = {30224732}, issn = {2045-2322}, mesh = {Animals ; Anxiety/*etiology/microbiology ; Colitis/etiology/microbiology/therapy ; Escherichia coli/*growth &amp; development ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Immobilization/*psychology ; Male ; Mice ; Mice, Inbred C57BL ; NF-kappa B/*metabolism ; Probiotics/administration &amp; dosage ; *Stress, Physiological ; }, abstract = {The present study aimed to understand the crosstalk between anxiety and gut microbiota. Exposure of mice to immobilization stress (IS) led to anxiety-like behaviors, increased corticosterone and tumor necrosis factor-α levels in the blood, increased nuclear factor (NF)-κB activation and microglia/monocyte populations in the hippocampus, and suppressed brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Furthermore, IS exposure increased NF-κB activation and monocyte population in the colon and increased Proteobacteria and Escherichia coli populations in the gut microbiota and fecal and blood lipopolysaccharide (LPS) levels while decreasing the lactobacilli population. Oral administration of the fecal microbiota of mice treated with IS (FIS) or E. coli led to the increased NF-κB activation and monocyte population in the colon. These treatments increased blood corticosterone and LPS levels and anxiety-like behaviors, decreased BDNF expression, and induced NF-κB activation and microglia/monocyte populations in the hippocampus. Intraperitoneal injection of LPS purified from E. coli also led to anxiety and colitis in mice. Oral administration of commensal lactobacilli, particularly Lactobacillus johnsonii, attenuated IS- or E. coli-induced colitis and anxiety-like behaviors and biomarkers. These findings suggest that exposure to stressors can increase Proteobacteria populations and fecal LPS levels and cause gastrointestinal inflammation, resulting in the deterioration of anxiety through NF-κB activation. However, the amelioration of gastrointestinal inflammation by treatment with probiotics including L. johnsonii can alleviate anxiety.}, }
@article {pmid30223665, year = {2018}, author = {Drastich, P and Bajer, L and Kverka, M}, title = {[Possibilities of therapeutic manipulation of the gut microbiota].}, journal = {Vnitrni lekarstvi}, volume = {64}, number = {6}, pages = {665-671}, pmid = {30223665}, issn = {0042-773X}, mesh = {Clostridioides difficile ; Clostridium Infections/therapy ; Dysbiosis ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Microbiota ; }, abstract = {Human gut microbiota, complex ecosystem of microbes associated with human gut, is essential for the development of the host's immune system and many other physiological functions. Recently, numerous diseases and syndromes were associated with disruption of this ecosystem thus stressing its importance in maintaining the host's health. Growing evidence suggests that by manipulating the gut microbiota, some of these diseases could be treated or even prevented. These manipulations include changes in diet, use of probiotics, prebiotics, antibiotics and fecal microbiota transplantation (FMT). The successes in FMT treatment of recurrent infection of Clostridium difficile led recently to a great interest in extending this treatment modality to other diseases with proven disruption of gut microbiota, such as ulcerative colitis or metabolic syndrome. Key words: Clostridium difficile - dysbiosis - fecal microbial transplantation - microbiota - prebiotics - probiotics.}, }
@article {pmid30221898, year = {2018}, author = {Reigadas, E and Olmedo, M and Valerio, M and Vázquez-Cuesta, S and Alcalá, L and Marín, M and Muñoz, P and Bouza, E}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection: Experience, protocol, and results.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {31}, number = {5}, pages = {411-418}, pmid = {30221898}, issn = {1988-9518}, mesh = {Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Bacteremia/etiology ; Capsules ; *Clostridioides difficile ; Colonoscopy ; Enterocolitis, Pseudomembranous/*microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Humans ; Intubation, Gastrointestinal ; Male ; *Microbiota ; Middle Aged ; Prospective Studies ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI). Despite its excellent efficacy, it is still not a routine procedure in most European centers. FMT has not been widely used in Spain to date. We describe our experience with FMT, including a novel approach based on oral fecal capsules.<br><br>METHODS: We analyzed a prospectively recorded case series of patients with R-CDI treated with FMT at a single center (June 2014-July 2017). Primary outcome was defined as resolution of CDI without recurrence in a two-month period. FMT was administered via colonoscopy, nasojejunal tube, or oral capsules. All stool donors were rigorously screened.<br><br>RESULTS: FMT was performed in 13 patients with R-CDI. Median age was 75.0 years and 76.9% were females. Six FMT were performed via nasojejunal tube, 5 via oral capsules, and 2 by colonoscopy. There were no procedure-related adverse events, except for bacteremia in one patient. During follow-up, R- CDI was observed in one patient at one month after FMT. The primary resolution rate was 83.3% and the overall resolution rate was 91.7%. FMT by capsules achieved a 100% resolution rate, colonoscopy 100%, and nasojejunal tube 80.0%.<br><br>CONCLUSIONS: In our cohort, FMT proved to be safe and effective, even in high risk patients. Oral administration in capsules also proved to be safe, well-tolerated, and highly effective for R-CDI. In our experience, the FMT capsule formulation seems feasible in the routine of a hospital. This administration method will allow FMT to be more widely used.}, }
@article {pmid30220458, year = {2018}, author = {Roediger, B and Lee, Q and Tikoo, S and Cobbin, JCA and Henderson, JM and Jormakka, M and O'Rourke, MB and Padula, MP and Pinello, N and Henry, M and Wynne, M and Santagostino, SF and Brayton, CF and Rasmussen, L and Lisowski, L and Tay, SS and Harris, DC and Bertram, JF and Dowling, JP and Bertolino, P and Lai, JH and Wu, W and Bachovchin, WW and Wong, JJ and Gorrell, MD and Shaban, B and Holmes, EC and Jolly, CJ and Monette, S and Weninger, W}, title = {An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis.}, journal = {Cell}, volume = {175}, number = {2}, pages = {530-543.e24}, pmid = {30220458}, issn = {1097-4172}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 DK107309/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Australia ; Disease Progression ; Female ; Fibrosis/pathology/virology ; Humans ; Kidney/metabolism/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Nephritis, Interstitial/physiopathology/*virology ; North America ; Parvoviridae Infections/metabolism ; Parvovirus/*isolation &amp; purification/*pathogenicity ; }, abstract = {The occurrence of a spontaneous nephropathy with intranuclear inclusions in laboratory mice has puzzled pathologists for over 4 decades, because its etiology remains elusive. The condition is more severe in immunodeficient animals, suggesting an infectious cause. Using metagenomics, we identify the causative agent as an atypical virus, termed "mouse kidney parvovirus" (MKPV), belonging to a divergent genus of Parvoviridae. MKPV was identified in animal facilities in Australia and North America, is transmitted via a fecal-oral or urinary-oral route, and is controlled by the adaptive immune system. Detailed analysis of the clinical course and histopathological features demonstrated a stepwise progression of pathology ranging from sporadic tubular inclusions to tubular degeneration and interstitial fibrosis and culminating in renal failure. In summary, we identify a widely distributed pathogen in laboratory mice and establish MKPV-induced nephropathy as a new tool for elucidating mechanisms of tubulointerstitial fibrosis that shares molecular features with chronic kidney disease in humans.}, }
@article {pmid30220230, year = {2018}, author = {Daniels, LM and Kufel, WD}, title = {Clinical review of Clostridium difficile infection: an update on treatment and prevention.}, journal = {Expert opinion on pharmacotherapy}, volume = {19}, number = {16}, pages = {1759-1769}, doi = {10.1080/14656566.2018.1524872}, pmid = {30220230}, issn = {1744-7666}, mesh = {Anti-Bacterial Agents/pharmacology/*therapeutic use ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/*drug therapy/pathology/*prevention &amp; control ; Humans ; Treatment Outcome ; }, abstract = {INTRODUCTION: Clostridium difficile infection (CDI) has become a significant healthcare-associated infection and is strongly associated with antibiotic use. Practice guidelines have recently been revised incorporating updated recommendations for diagnosis, treatment, and prevention.<br><br>AREAS COVERED: This review discusses updated aspects of CDI management. New and emerging pharmacologic options for treatment and prevention are reviewed.<br><br>EXPERT OPINION: Metronidazole is associated with lower rates of treatment success compared to vancomycin and should no longer be used as primary therapy for the first episode of CDI or recurrent disease. Vancomycin or fidaxomicin are now recommended for first-line therapy for most cases of CDI. Fecal microbiota transplant is effective and safe for the treatment of recurrent CDI. Evidence supports the use of fidaxomicin and bezlotoxumab for prevention of recurrent CDI; however, the costs associated with these therapies may limit their use. Validated risk prediction tools are needed to identify patients most likely to benefit from these treatments. Future advancements in microbiota targeting treatments will emerge as promising alternatives to standard CDI treatments. Antibiotic stewardship and infection control measures will remain essential components for CDI management.}, }
@article {pmid30219368, year = {2018}, author = {Miyazaki, A and Kandasamy, S and Michael, H and Langel, SN and Paim, FC and Chepngeno, J and Alhamo, MA and Fischer, DD and Huang, HC and Srivastava, V and Kathayat, D and Deblais, L and Rajashekara, G and Saif, LJ and Vlasova, AN}, title = {Protein deficiency reduces efficacy of oral attenuated human rotavirus vaccine in a human infant fecal microbiota transplanted gnotobiotic pig model.}, journal = {Vaccine}, volume = {36}, number = {42}, pages = {6270-6281}, pmid = {30219368}, issn = {1873-2518}, support = {R01 AI099451/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Feces/*microbiology ; *Germ-Free Life ; Humans ; Infant ; Microbiota/immunology ; Protein Deficiency/*complications/immunology/metabolism ; Rotavirus/immunology/pathogenicity ; Rotavirus Vaccines/therapeutic use ; Swine ; Tryptophan/metabolism ; Vaccines, Attenuated/*therapeutic use ; }, abstract = {BACKGROUND: Low efficacy of rotavirus (RV) vaccines in developing African and Asian countries, where malnutrition is prevalent, remains a major concern and a challenge for global health.<br><br>METHODS: To understand the effects of protein malnutrition on RV vaccine efficacy, we elucidated the innate, T cell and cytokine immune responses to attenuated human RV (AttHRV) vaccine and virulent human RV (VirHRV) challenge in germ-free (GF) pigs or human infant fecal microbiota (HIFM) transplanted gnotobiotic (Gn) pigs fed protein-deficient or -sufficient bovine milk diets. We also analyzed serum levels of tryptophan (TRP), a predictor of malnutrition, and kynurenine (KYN).<br><br>RESULTS: Protein-deficient pigs vaccinated with oral AttHRV vaccine had lower protection rates against diarrhea post-VirHRV challenge and significantly increased fecal virus shedding titers (HIFM transplanted but not GF pigs) compared with their protein-sufficient counterparts. Reduced vaccine efficacy in protein-deficient pigs coincided with altered serum IFN-&#x3b1;, TNF-&#x3b1;, IL-12 and IFN-&#x3b3; responses to oral AttHRV vaccine and the suppression of multiple innate immune parameters and HRV-specific IFN-&#x3b3; producing T cells post-challenge. In protein-deficient HIFM transplanted pigs, decreased serum KYN, but not TRP levels were observed throughout the experiment, suggesting an association between the altered TRP metabolism and immune responses.<br><br>CONCLUSION: Collectively, our findings confirm the negative effects of protein deficiency, which were exacerbated in the HIFM transplanted pigs, on innate, T cell and cytokine immune responses to HRV and on vaccine efficacy, as well as on TRP-KYN metabolism.}, }
@article {pmid30218939, year = {2018}, author = {Schmulson, M and Bashashati, M}, title = {Fecal microbiota transfer for bowel disorders: efficacy or hype?.}, journal = {Current opinion in pharmacology}, volume = {43}, number = {}, pages = {72-80}, doi = {10.1016/j.coph.2018.08.012}, pmid = {30218939}, issn = {1471-4973}, mesh = {Animals ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Feces/*microbiology ; Gastrointestinal Diseases/diagnosis/microbiology/physiopathology/*therapy ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology/physiopathology ; Recovery of Function ; Risk Factors ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Dysbiosis has been related to the pathophysiology of disorders of - gut-brain interaction (DGBI) including irritable bowel syndrome (IBS) and functional constipation (FC). Accordingly, modulation of gut microbiota has been proposed as a potential treatment for these disorders. Gut microbiota modulation can be effected by probiotics, prebiotics, symbiotics, postbiotics, antibiotics and fecal transplantation (FMT) or bacteriotherapy. The latter is currently used for recurrent or severe Clostridium difficile colitis and has been the focus of recent research in IBS and FC.<br><br>RECENT FINDINGS: Several case series reported promising results for FMT in patients with IBS and FC, which prompted the conduction of randomized controlled trials (RCT) in these DGBI.<br><br>SUMMARY: Both case series and RCTs are herein discussed. To the best of our knowledge, as of yet, 5 RCTs have been published on IBS and one in FC with slow colonic transit. In IBS, the majority of studies have used the IBS severity scoring system (IBS-SSS) as an outcome measure; however, the selection criteria were different among the trials as well as the route and form of administration of the FMT. Therefore, the results are inconsistent and no conclusion can be drawn. Some studies suggest that the presence of post-infection (PI)-IBS and the baseline microbiota status in the donors could be predictor factors of successful FMT in IBS. In constipation with slow colonic transit, the FMT seems to be more effective, although the data is based on only one RCT. We believe that larger RCTs, controlled with true placebos and considering baseline intestinal microbiota of the study subjects as well as donors' microbiota are still needed before recommending FMT in IBS and/or FC. History of previous GI infection (e.g. PI-IBS) and IBS subtypes should also be taken into account.}, }
@article {pmid30216124, year = {2018}, author = {Diorio, C and Robinson, PD and Ammann, RA and Castagnola, E and Erickson, K and Esbenshade, A and Fisher, BT and Haeusler, GM and Kuczynski, S and Lehrnbecher, T and Phillips, R and Cabral, S and Dupuis, LL and Sung, L}, title = {Guideline for the Management of Clostridium Difficile Infection in Children and Adolescents With Cancer and Pediatric Hematopoietic Stem-Cell Transplantation Recipients.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {36}, number = {31}, pages = {3162-3171}, pmid = {30216124}, issn = {1527-7755}, support = {G0800472/MRC_/Medical Research Council/United Kingdom ; K12 CA090625/CA/NCI NIH HHS/United States ; PDF-2014-07-072/DH_/Department of Health/United Kingdom ; }, abstract = {PURPOSE: The aim of this work was to develop a clinical practice guideline for the prevention and treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients.<br><br>METHODS: An international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations.<br><br>RESULTS: The panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research.<br><br>CONCLUSION: We present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population.}, }
@article {pmid30215149, year = {2018}, author = {Sircana, A and Framarin, L and Leone, N and Berrutti, M and Castellino, F and Parente, R and De Michieli, F and Paschetta, E and Musso, G}, title = {Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?.}, journal = {Current diabetes reports}, volume = {18}, number = {10}, pages = {98}, pmid = {30215149}, issn = {1539-0829}, mesh = {Animals ; Diabetes Mellitus, Type 2/*microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Inflammation/pathology ; Metabolome ; }, abstract = {PURPOSE OF REVIEW: In the last decade many studies have suggested an association between the altered gut microbiota and multiple systemic diseases including diabetes. In this review, we will discuss potential pathophysiological mechanisms, the latest findings regarding the mechanisms linking gut dysbiosis and type 2 diabetes (T2D), and the results obtained with experimental modulation of microbiota.<br><br>RECENT FINDINGS: In T2D, gut dysbiosis contributes to onset and maintenance of insulin resistance. Different strategies that reduce dysbiosis can improve glycemic control. Evidence in animals and humans reveals differences between the gut microbial composition in healthy individuals and those with T2D. Changes in the intestinal ecosystem could cause inflammation, alter intestinal permeability, and modulate metabolism of bile acids, short-chain fatty acids and metabolites that act synergistically on metabolic regulation systems contributing to insulin resistance. Interventions that restore equilibrium in the gut appear to have beneficial effects and improve glycemic control. Future research should examine in detail and in larger studies other possible pathophysiological mechanisms to identify specific pathways modulated by microbiota modulation and identify new potential therapeutic targets.}, }
@article {pmid30214266, year = {2018}, author = {Sunkara, T and Rawla, P and Ofosu, A and Gaduputi, V}, title = {Fecal microbiota transplant - a new frontier in inflammatory bowel disease.}, journal = {Journal of inflammation research}, volume = {11}, number = {}, pages = {321-328}, pmid = {30214266}, issn = {1178-7031}, abstract = {Inflammatory bowel disease (IBD) is a chronic multifactorial disease that affects the gastrointestinal tract and results from an aberrant immune response toward luminal antigens in genetically susceptible people. Most of the current therapies for IBD focus on the management of the inflammation by using corticosteroids, immune modulators, and more recently, monoclonal antibodies (biological therapy). Although these therapies provide benefit in most cases, there are still a significant number of patients who do not respond or become refractory over time, suggesting the need for alternative therapeutic options. In the last decade, it has been recognized that "dysbiosis," an imbalanced gut microbiota, is a key element in IBD suggesting microbiome-based therapies as an attractive approach. Recently, fecal microbiota transplant (FMT) has been successfully used for the treatment of Clostridium difficile infection, and it is now under investigation for the treatment of IBD. Clinical trials data are still poor but strongly support a future introduction of FMT in therapy to manage IBD microbiome. More studies are needed to assess the optimal route of administration and the frequency of FMT, the best matched donor for each patient as well as the risks associated with FMT in IBD.}, }
@article {pmid30213614, year = {2019}, author = {Samuelson, DR and Siggins, RW and Ruan, S and Amedee, AM and Sun, J and Zhu, QK and Marasco, WA and Taylor, CM and Luo, M and Welsh, DA and Shellito, JE}, title = {Alcohol consumption increases susceptibility to pneumococcal pneumonia in a humanized murine HIV model mediated by intestinal dysbiosis.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {80}, number = {}, pages = {33-43}, pmid = {30213614}, issn = {1873-6823}, support = {P60 AA009803/AA/NIAAA NIH HHS/United States ; K99 AA026336/AA/NIAAA NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; P01 HL076100/HL/NHLBI NIH HHS/United States ; UH2 AA026226/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Bone Marrow Transplantation ; CD4 Lymphocyte Count ; Disease Models, Animal ; Disease Susceptibility/*chemically induced/microbiology/virology ; Dysbiosis/*microbiology/virology ; Ethanol/*adverse effects ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; HIV Infections/*complications ; Hematopoietic Stem Cell Transplantation ; Humans ; Liver Transplantation ; Mice ; Pneumonia, Pneumococcal/*etiology ; RNA, Ribosomal, 16S/genetics ; Thymus Gland/transplantation ; Transplantation, Heterologous ; Viral Load/drug effects ; }, abstract = {Alcohol use in persons living with HIV (PLWH) worsens the severity of bacterial pneumonia. However, the exact mechanism(s) by which this occurs remain ill-defined. We hypothesized that alcohol in the setting of HIV infection decreases Streptococcus pneumoniae clearance from the lung through mechanisms mediated by the gut microbiota. Humanized BLT (bone marrow, liver, thymus) mice were infected with 1 × 10[4] TCID50 of HIV (BAL and JRCSF strains) via intraperitoneal (i.p.) injection. One week post-HIV infection, animals were switched to a Lieber-DeCarli 5% ethanol diet or an isocaloric control diet for 10 days. Alcohol-fed animals were also given two binges of 2 g/kg ethanol on days 5 and 10. Feces were also collected, banked, and the community structures were analyzed. Mice were then infected with 1 × 10[5] CFU (colony-forming units) of S. pneumoniae and were sacrificed 48 h later. HIV-infected mice had viral loads of ∼2 × 10[4] copies/mL of blood 1 week post-infection, and exhibited an ∼57% decrease in the number of circulating CD4+ T cells at the time of sacrifice. Fecal microbial community structure was significantly different in each of the feeding groups, as well as with HIV infection. Alcohol-fed mice had a significantly higher burden of S. pneumoniae 48 h post-infection, regardless of HIV status. In follow-up experiments, female C57BL/6 mice were treated with a cocktail of antibiotics daily for 2 weeks and recolonized by gavage with intestinal microbiota from HIV+ ethanol-fed, HIV+ pair-fed, HIV- ethanol-fed, or HIV- pair-fed mice. Recolonized mice were then infected with S. pneumoniae and were sacrificed 48 h later. The intestinal microbiota from alcohol-fed mice (regardless of HIV status) significantly impaired clearance of S. pneumoniae. Collectively, these data indicate that alcohol feeding, as well as alcohol-associated intestinal dysbiosis, compromise pulmonary host defenses against pneumococcal pneumonia. Determining whether HIV infection acts synergistically with alcohol use in impairing pulmonary host defenses will require additional study.}, }
@article {pmid30213273, year = {2018}, author = {Frudinger, A and Marksteiner, R and Pfeifer, J and Margreiter, E and Paede, J and Thurner, M}, title = {Skeletal muscle-derived cell implantation for the treatment of sphincter-related faecal incontinence.}, journal = {Stem cell research &amp; therapy}, volume = {9}, number = {1}, pages = {233}, pmid = {30213273}, issn = {1757-6512}, mesh = {Aged ; Anal Canal/pathology/*surgery ; Cryopreservation/methods ; Fecal Incontinence/pathology/psychology/*surgery ; Female ; Humans ; Male ; Middle Aged ; Muscle Fibers, Skeletal/cytology/physiology/*transplantation ; Muscle, Skeletal/cytology/physiology ; Pregnancy ; Quality of Life/*psychology ; Transplantation, Autologous ; Treatment Outcome ; }, abstract = {BACKGROUND: In an earlier pilot study with 10 women, we investigated a new approach for therapy of faecal incontinence (FI) due to obstetric trauma, involving ultrasound-guided injection of autologous skeletal muscle-derived cells (SMDC) into the external anal sphincter (EAS), and observed significant improvement. In the current study, we tested this therapeutic approach in an extended patient group: male and female patients suffering from FI due to EAS damage and/or atrophy. Furthermore, feasibility of lower cell counts and cryo-preserved SMDC was assessed.<br><br>METHODS: In this single-centre, explorative, baseline-controlled clinical trial, each patient (n&#x2009;=&#x2009;39; mean age 60.6&#x2009;&#xb1;&#x2009;13.81&#xa0;years) received 79.4&#x2009;&#xb1;&#x2009;22.5&#x2009;&#xd7;&#x2009;10[6] cryo-preserved autologous SMDC. Changes in FI parameters, Fecal Incontinence Quality of Life (FIQL), anorectal manometry and safety from baseline to 1, 6 and 12&#xa0;months post implantation were evaluated.<br><br>RESULTS: SMDC used in this trial contained a high percentage of myogenic-expressing (CD56[+]) and muscle stem cell marker-expressing (Pax7[+], Myf5[+]) cells. Intervention was well tolerated without any serious adverse events. After 12&#xa0;months, the number of weekly incontinence episodes (WIE, primary variable), FIQL and patient condition had improved significantly. In 80.6% of males and 78.4% of females, the WIE frequency decreased by at least 50%; Wexner scores and severity of FI complaints decreased significantly, independent of gender and cause of FI.<br><br>CONCLUSIONS: Injection of SMDCs into the EAS effectively improved sphincter-related FI due to EAS damage and/or atrophy in males and females. When confirmed in a larger, placebo-controlled trial, this minimal invasive procedure has the potential to become first-line therapy for FI.<br><br>TRIAL REGISTRATION: EU Clinical Trials Register, EudraCT 2010-023826-19&#xa0;(Date of registration: 08.11.2010).}, }
@article {pmid30212271, year = {2019}, author = {Ossorio, PN and Zhou, Y}, title = {Regulating stool for microbiota transplantation.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {105-108}, pmid = {30212271}, issn = {1949-0984}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {In 2017 Gut Microbes published "A proposed definition of microbiota transplantation for regulatory purposes," in which the authors suggest that regulators should draw a line between microbiota transplants and biologic drugs composed of microbial communities (or other products derived from the human microbiome). They develop a definition of microbiota transplantation (MT) to help regulators draw such a line, and suggest that MT need not be, and cannot be, regulated as a biologic drug (a live biotherapeutic product). However, an agency's regulatory scrutiny of a medical product should be commensurate with that product's degree of risk to patients. Products for MT, such as stool, are likely to be as or more dangerous than more highly manipulated microbial products that scientists and regulators agree should be regulated as biologic drugs. Therefore, we argue that MT, as defined by the authors, should receive the same regulatory oversight as any other biologic product intended to cure, mitigate, treat, or prevent disease. We also suggest that regulators might not be able to operationalize the proposed definition of MT.}, }
@article {pmid30210803, year = {2018}, author = {Wang, Z and Lou, H and Wang, Y and Shamir, R and Jiang, R and Chen, T}, title = {GePMI: A statistical model for personal intestinal microbiome identification.}, journal = {NPJ biofilms and microbiomes}, volume = {4}, number = {}, pages = {20}, pmid = {30210803}, issn = {2055-5008}, abstract = {Human gut microbiomes consist of a large number of microbial genomes, which vary by diet and health conditions and from individual to individual. In the present work, we asked whether such variation or similarity could be measured and, if so, whether the results could be used for personal microbiome identification (PMI). To address this question, we herein propose a method to estimate the significance of similarity among human gut metagenomic samples based on reference-free, long k-mer features. Using these features, we find that pairwise similarities between the metagenomes of any two individuals obey a beta distribution and that a p value derived accordingly well characterizes whether two samples are from the same individual or not. We develop a computational framework called GePMI (Generating inter-individual similarity distribution for Personal Microbiome Identification) and apply it to several human gut metagenomic datasets (>300 individuals and >600 samples in total). From the results of GePMI, most of the human gut microbiomes can be identified (auROC = 0.9470, auPRC = 0.8702). Even after antibiotic treatment or fecal microbiota transplantation, the individual k-mer signature still maintains a certain specificity.}, }
@article {pmid30209919, year = {2018}, author = {Cobo, J}, title = {A comprehensive approach for the patient with Clostridium difficile infection.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {31 Suppl 1}, number = {Suppl 1}, pages = {27-31}, pmid = {30209919}, issn = {1988-9518}, mesh = {Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile ; Clostridium Infections/*drug therapy/microbiology/therapy ; Humans ; }, abstract = {During the last decade there have been many changes and advances in the research on Clostridium difficile infection (CDI). We have improved diagnostic and therapeutic tools and, at the same time, we have learned that the CDI implies, especially in the most vulnerable patients, an important morbidity. CDI has traditionally been undervalued and it is widely dispersed in hospitals. Surely, there is inertness in its management and there are also broad areas of improvement. If we add to this the high cost of the new drugs and the practical difficulties to implement the faecal microbiota transplant, we realize that we may not be taking full advantage of all the opportunities to improve patient's outcomes. The implementation of policies that favour the supervision of all CDI cases by an expert in infectious diseases will contribute to a better global management of this important disease.}, }
@article {pmid30208195, year = {2018}, author = {Noor, A and Krilov, LR}, title = {Clostridium difficile Infection in Children.}, journal = {Pediatric annals}, volume = {47}, number = {9}, pages = {e359-e365}, doi = {10.3928/19382359-20180803-01}, pmid = {30208195}, issn = {1938-2359}, mesh = {Child ; *Clostridium Infections/diagnosis/epidemiology/microbiology/therapy ; Cross Infection/diagnosis/epidemiology/microbiology/therapy ; Humans ; Incidence ; Infection Control/methods ; Recurrence ; Risk Factors ; United States/epidemiology ; }, abstract = {Clostridium difficile is an important cause of health care associated infections. The epidemiology of C. difficile infection (CDI) in children has changed over the past few decades. There is now a higher incidence in hospitalized children, and there has been an emergence of community-onset infection. A hypervirulent strain, North American pulse type 1, has also developed. Neonates and young infants have high rates of colonization but rarely have symptoms. The well-known risk factor for CDI in children age 2 years or older is antibiotic use. Inflammatory bowel disease and cancer are associated with increased incidence and severity of CDI. Nucleic acid amplification tests are now widely used for diagnosis given their rapid turnover and higher sensitivity and specificity. The treatment for an initial episode and first recurrence is oral metronidazole. Oral vancomycin is reserved for second recurrence or severe cases. A new treatment option, fecal bowel transplant, has been reported to be safe and effective in adults, and studies are now being conducted in children. [Pediatr Ann. 2018;47(9):e359-e365.].}, }
@article {pmid30202057, year = {2018}, author = {Zuo, T and Wong, SH and Cheung, CP and Lam, K and Lui, R and Cheung, K and Zhang, F and Tang, W and Ching, JYL and Wu, JCY and Chan, PKS and Sung, JJY and Yu, J and Chan, FKL and Ng, SC}, title = {Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {3663}, pmid = {30202057}, issn = {2041-1723}, mesh = {Adult ; Animals ; Anti-Bacterial Agents/therapeutic use ; Aspergillus ; Candida albicans ; Clostridioides difficile ; Clostridium Infections/*therapy ; Dysbiosis/*complications ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Multivariate Analysis ; RNA, Ribosomal, 16S/genetics ; Recurrence ; Saccharomyces ; }, abstract = {Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infection (CDI). Bacterial colonization in recipients after FMT has been studied, but little is known about the role of the gut fungal community, or mycobiota. Here, we show evidence of gut fungal dysbiosis in CDI, and that donor-derived fungal colonization in recipients is associated with FMT response. CDI is accompanied by over-representation of Candida albicans and decreased fungal diversity, richness, and evenness. Cure after FMT is associated with increased colonization of donor-derived fungal taxa in recipients. Recipients of successful FMT ("responders") display, after FMT, a high relative abundance of Saccharomyces and Aspergillus, whereas "nonresponders" and individuals treated with antibiotics display a dominant presence of Candida. High abundance of C. albicans in donor stool also correlates with reduced FMT efficacy. Furthermore, C. albicans reduces FMT efficacy in a mouse model of CDI, while antifungal treatment reestablishes its efficacy, supporting a potential causal relationship between gut fungal dysbiosis and FMT outcome.}, }
@article {pmid30197631, year = {2018}, author = {Wei, YL and Chen, YQ and Gong, H and Li, N and Wu, KQ and Hu, W and Wang, B and Liu, KJ and Wen, LZ and Xiao, X and Chen, DF}, title = {Fecal Microbiota Transplantation Ameliorates Experimentally Induced Colitis in Mice by Upregulating AhR.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1921}, pmid = {30197631}, issn = {1664-302X}, abstract = {Ulcerative colitis (UC) is a chronic non-specific inflammatory disease that occurs in the colon and rectum. While fecal microbiota transplantation (FMT) is gaining attention as a clinical treatment of UC, the molecular mechanisms behind this effect have yet to be fully understood. A C57BL/6 mouse model was established to test whether FMT promotes the recovery of colon inflammation. Administration of 2% dextran sulfate sodium (DSS) for 7 days successfully induced acute colitis, as evidenced by diarrhea, hematochezia and colon shortening as well as a decrease in body weight. FMT alleviated the severity of colon mucosa injury and improved histological alterations compared with that of the DSS group. In addition, FMT promoted homeostasis of the intestinal microbiota. Furthermore, FMT upregulated the expression of aryl hydrocarbon receptor (AHR), interleukin-10 (IL-10), and transforming growth factor beta (TGF-β) in colon tissues. These results suggest that the significant anti-inflammatory effect of FMT may be attributed to its promotion of IL-10 and TGF-β production and AHR activation. Based on these results, FMT had a favorable therapeutic effect on DSS-induced colitis.}, }
@article {pmid30196243, year = {2018}, author = {Mukherjee, S and Joardar, N and Sengupta, S and Sinha Babu, SP}, title = {Gut microbes as future therapeutics in treating inflammatory and infectious diseases: Lessons from recent findings.}, journal = {The Journal of nutritional biochemistry}, volume = {61}, number = {}, pages = {111-128}, pmid = {30196243}, issn = {1873-4847}, mesh = {Autoimmune Diseases/microbiology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/*microbiology/therapy ; Gastrointestinal Microbiome/immunology/*physiology ; Host-Pathogen Interactions/immunology ; Humans ; Hypersensitivity/microbiology/therapy ; Infections/*microbiology ; Inflammatory Bowel Diseases/microbiology/therapy ; Neoplasms/microbiology ; }, abstract = {The human gut microbiota has been the interest of extensive research in recent years and our knowledge on using the potential capacity of these microbes are growing rapidly. Microorganisms colonized throughout the gastrointestinal tract of human are coevolved through symbiotic relationship and can influence physiology, metabolism, nutrition and immune functions of an individual. The gut microbes are directly involved in conferring protection against pathogen colonization by inducing direct killing, competing with nutrients and enhancing the response of the gut-associated immune repertoire. Damage in the microbiome (dysbiosis) is linked with several life-threatening outcomes viz. inflammatory bowel disease, cancer, obesity, allergy, and auto-immune disorders. Therefore, the manipulation of human gut microbiota came out as a potential choice for therapeutic intervention of the several human diseases. Herein, we review significant studies emphasizing the influence of the gut microbiota on the regulation of host responses in combating infectious and inflammatory diseases alongside describing the promises of gut microbes as future therapeutics.}, }
@article {pmid30195459, year = {2018}, author = {Gustot, T and Moreau, R}, title = {Acute-on-chronic liver failure vs. traditional acute decompensation of cirrhosis.}, journal = {Journal of hepatology}, volume = {69}, number = {6}, pages = {1384-1393}, doi = {10.1016/j.jhep.2018.08.024}, pmid = {30195459}, issn = {1600-0641}, mesh = {Acute-On-Chronic Liver Failure/*etiology/immunology/mortality/*therapy ; Adult ; Cell- and Tissue-Based Therapy ; Fecal Microbiota Transplantation ; Female ; Humans ; Immunomodulation ; Liver Cirrhosis/*complications/etiology/virology ; *Liver Transplantation ; Prognosis ; *Renal Dialysis ; Severity of Illness Index ; Treatment Outcome ; }, }
@article {pmid30194287, year = {2018}, author = {Luo, Y and Zeng, B and Zeng, L and Du, X and Li, B and Huo, R and Liu, L and Wang, H and Dong, M and Pan, J and Zheng, P and Zhou, C and Wei, H and Xie, P}, title = {Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus.}, journal = {Translational psychiatry}, volume = {8}, number = {1}, pages = {187}, pmid = {30194287}, issn = {2158-3188}, mesh = {Animals ; Anxiety/*microbiology ; *Behavior, Animal ; Depression/*microbiology ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Hippocampus/*metabolism ; Hydrocortisone/blood ; Hypothalamo-Hypophyseal System/microbiology/physiology ; Male ; Mice ; Mice, Inbred BALB C ; Pituitary-Adrenal System/microbiology/physiology ; Receptors, Glucocorticoid/*metabolism ; Stress, Psychological/microbiology ; }, abstract = {Gut microbiota has an important role in the immune system, metabolism, and digestion, and has a significant effect on the nervous system. Recent studies have revealed that abnormal gut microbiota induces abnormal behaviors, which may be associated with the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, we investigated the behavioral changes in germ-free (GF) mice by behavioral tests, quantified the basal serum cortisol levels, and examined glucocorticoid receptor pathway genes in hippocampus using microarray analysis followed by real-time PCR validation, to explore the molecular mechanisms by which the gut microbiota influences the host's behaviors and brain function. Moreover, we quantified the basal serum cortisol levels and validated the differential genes in an Escherichia coli-derived lipopolysaccharide (LPS) treatment mouse model and fecal "depression microbiota" transplantation mouse model by real-time PCR. We found that GF mice showed antianxiety- and antidepressant-like behaviors, whereas E. coli LPS-treated mice showed antidepressant-like behavior, but did not show antianxiety-like behavior. However, "depression microbiota" recipient mice exhibited anxiety- and depressive-like behaviors. In addition, six glucocorticoid receptor pathway genes (Slc22a5, Aqp1, Stat5a, Ampd3, Plekhf1, and Cyb561) were upregulated in GF mice, and of these only two (Stat5a and Ampd3) were upregulated in LPS-treated mice, whereas the shared gene, Stat5a, was downregulated in "depression microbiota" recipient mice. Furthermore, basal serum cortisol levels were decreased in E. coli LPS-treated mice but not in GF mice and "depression microbiota" recipient mice. These results indicated that the gut microbiota may lead to behavioral abnormalities in mice through the downstream pathway of the glucocorticoid receptor. Herein, we proposed a new insight into the molecular mechanisms by which gut microbiota influence depressive-like behavior.}, }
@article {pmid30193113, year = {2018}, author = {Suez, J and Zmora, N and Zilberman-Schapira, G and Mor, U and Dori-Bachash, M and Bashiardes, S and Zur, M and Regev-Lehavi, D and Ben-Zeev Brik, R and Federici, S and Horn, M and Cohen, Y and Moor, AE and Zeevi, D and Korem, T and Kotler, E and Harmelin, A and Itzkovitz, S and Maharshak, N and Shibolet, O and Pevsner-Fischer, M and Shapiro, H and Sharon, I and Halpern, Z and Segal, E and Elinav, E}, title = {Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT.}, journal = {Cell}, volume = {174}, number = {6}, pages = {1406-1423.e16}, doi = {10.1016/j.cell.2018.08.047}, pmid = {30193113}, issn = {1097-4172}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Animals ; Anti-Bacterial Agents/*pharmacology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intestinal Mucosa/drug effects/microbiology ; Lactobacillus/drug effects/genetics/isolation &amp; purification ; Lactococcus/genetics/isolation &amp; purification ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Probiotics/*administration &amp; dosage ; RNA, Ribosomal, 16S/analysis/genetics/metabolism ; Young Adult ; }, abstract = {Probiotics are widely prescribed for prevention of antibiotics-associated dysbiosis and related adverse effects. However, probiotic impact on post-antibiotic reconstitution of the gut mucosal host-microbiome niche remains elusive. We invasively examined the effects of multi-strain probiotics or autologous fecal microbiome transplantation (aFMT) on post-antibiotic reconstitution of the murine and human mucosal microbiome niche. Contrary to homeostasis, antibiotic perturbation enhanced probiotics colonization in the human mucosa but only mildly improved colonization in mice. Compared to spontaneous post-antibiotic recovery, probiotics induced a markedly delayed and persistently incomplete indigenous stool/mucosal microbiome reconstitution and host transcriptome recovery toward homeostatic configuration, while aFMT induced a rapid and near-complete recovery within days of administration. In vitro, Lactobacillus-secreted soluble factors contributed to probiotics-induced microbiome inhibition. Collectively, potential post-antibiotic probiotic benefits may be offset by a compromised gut mucosal recovery, highlighting a need of developing aFMT or personalized probiotic approaches achieving mucosal protection without compromising microbiome recolonization in the antibiotics-perturbed host.}, }
@article {pmid30191611, year = {2019}, author = {Mullaney, JA and Stephens, JE and Geeling, BE and Hamilton-Williams, EE}, title = {Early-life exposure to gut microbiota from disease-protected mice does not impact disease outcome in type 1 diabetes susceptible NOD mice.}, journal = {Immunology and cell biology}, volume = {97}, number = {1}, pages = {97-103}, doi = {10.1111/imcb.12201}, pmid = {30191611}, issn = {1440-1711}, mesh = {Age Factors ; Animals ; Animals, Newborn ; Diabetes Mellitus, Type 1/*immunology/microbiology/prevention &amp; control ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {The microbial community making up the gut microbiota can profoundly influence intestinal homeostasis and immune system development, and is believed to influence the development of complex diseases including type 1 diabetes (T1D). T1D susceptible nonobese diabetic (NOD) mice have been shown to harbor a distinct microbiota to disease-protected mice. We hypothesized that the T1D susceptible genetic background of NOD mice would be resistant to the introduction of a C57BL/6-derived microbiota. NOD and C57BL/6 mice were cohoused either continually from birth, from birth until weaning or from weaning onwards, allowing transfer of microbiota between the mice. Cohousing NOD with C57BL/6 mice from before birth, resulted in moderate changes to the gut microbiota, whereas initiating cohousing at weaning only led to minimal changes. Terminating cohousing at weaning reduced the changes in the microbiota composition. However, diabetes onset was not significantly delayed and there was no reduction in intestinal inflammation or the proportion of regulatory T cells in the cohoused NOD mice. However, insulin but not islet-specific glucose-6-phosphatase catalytic subunit-related protein-specific CD8[+] T cells were reduced by cohousing suggesting an epitope-specific modulation of the autoreactive response by the gut microbiota. These results suggest that the T1D susceptible genetic background of the NOD mouse was resistant to the introduction of a C57BL/6-derived microbiota.}, }
@article {pmid30189736, year = {2018}, author = {Tutková, M and Rudá-Kučerová, J}, title = {Microbiome in connection with metabolic syndrome and the therapeutic potential of its influencing.}, journal = {Ceska a Slovenska farmacie : casopis Ceske farmaceuticke spolecnosti a Slovenske farmaceuticke spolecnosti}, volume = {67}, number = {2}, pages = {71-80}, pmid = {30189736}, issn = {1210-7816}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Metabolic Syndrome/*microbiology ; Prebiotics ; Probiotics ; }, abstract = {Several fields of medicine have been concerned with the role of the microbiome in maintaining the balance in the human body and its changes in the pathogenesis of diseases in recent years. The intestinal microbiome seems to play a key role in the regulation of metabolic pathways, inflammation and intestinal permeability. The aim of this review is to assess the importance of the intestinal microbiome in metabolic syndrome and the therapeutic or preventive potential of its manipulation. Key words: metabolic syndrome • microbiome • probiotics • prebiotics • fecal transplant.}, }
@article {pmid30188944, year = {2018}, author = {Sullender, ME and Baldridge, MT}, title = {Norovirus interactions with the commensal microbiota.}, journal = {PLoS pathogens}, volume = {14}, number = {9}, pages = {e1007183}, pmid = {30188944}, issn = {1553-7374}, support = {K22 AI127846/AI/NIAID NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Caliciviridae Infections/*etiology/immunology/*microbiology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastroenteritis/etiology/immunology/microbiology ; Gastrointestinal Microbiome/immunology/*physiology ; Host-Pathogen Interactions/immunology/physiology ; Humans ; Mice ; Norovirus/immunology/*pathogenicity ; }, }
@article {pmid30183502, year = {2019}, author = {Strouse, C and Mangalam, A and Zhang, J}, title = {Bugs in the system: bringing the human microbiome to bear in cancer immunotherapy.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {109-112}, pmid = {30183502}, issn = {1949-0984}, support = {P30 CA086862/CA/NCI NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Dysbiosis/immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; *Immunotherapy ; Microbiota/drug effects/genetics/*immunology ; Neoplasms/immunology/*microbiology/*therapy ; }, abstract = {The influence of the composition of the human microbiome on the efficacy of cancer directed immunotherapies, such as antibodies directed against the programmed cell death 1 protein (PD-1) or its ligand (PD-L1), has garnered increasing attention as the role of immunotherapies in the care of cancer has grown. Dysbiosis (altered microbiota) has recently been reported to adversely affect the efficacy of cancer directed immunotherapies, and correction of this dysbiosis has the potential to improve the efficacy of these treatments. However, the exact mechanisms underlying this relationship remains unknown. Current methods for characterizing the microbiome likely capture only a small portion of the highly complex interaction between the microbiome and the immune system. Here we discuss the recent reports of the influence of dysbiosis on cancer immunotherapy, methods to more fully characterize the interaction between the microbiome and the immune system, and methods of modulating the immune system to improve the efficacy of cancer immunotherapy.}, }
@article {pmid30183484, year = {2019}, author = {Monaghan, T and Mullish, BH and Patterson, J and Wong, GK and Marchesi, JR and Xu, H and Jilani, T and Kao, D}, title = {Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {142-148}, pmid = {30183484}, issn = {1949-0984}, support = {MC_PC_17162/MRC_/Medical Research Council/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Aged ; Bile Acids and Salts/*metabolism ; Clostridioides difficile/genetics ; Clostridium Infections/metabolism/*therapy ; *Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Female ; Fibroblast Growth Factors/*metabolism ; Gastrointestinal Microbiome/genetics ; Humans ; Male ; Middle Aged ; Proteome/metabolism ; Receptors, Cytoplasmic and Nuclear/*metabolism ; Recurrence ; *Signal Transduction ; Treatment Outcome ; Weight Gain ; }, abstract = {The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.}, }
@article {pmid30181578, year = {2018}, author = {Yitbarek, A and Taha-Abdelaziz, K and Hodgins, DC and Read, L and Nagy, &#xc9; and Weese, JS and Caswell, JL and Parkinson, J and Sharif, S}, title = {Gut microbiota-mediated protection against influenza virus subtype H9N2 in chickens is associated with modulation of the innate responses.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {13189}, pmid = {30181578}, issn = {2045-2322}, mesh = {Animals ; Chickens/*immunology/microbiology/virology ; *Gastrointestinal Microbiome ; Immunity, Innate ; Influenza A Virus, H9N2 Subtype/*immunology ; Influenza in Birds/*immunology/microbiology/virology ; Interferon Type I/immunology ; }, abstract = {Commensal gut microbiota plays an important role in health and disease. The current study was designed to assess the role of gut microbiota of chickens in the initiation of antiviral responses against avian influenza virus. Day-old layer chickens received a cocktail of antibiotics for 12 (ABX-D12) or 16 (ABX-D16) days to deplete their gut microbiota, followed by treatment of chickens from ABX-12 with five Lactobacillus species combination (PROB), fecal microbial transplant suspension (FMT) or sham treatment daily for four days. At day 17 of age, chickens were challenged with H9N2 virus. Cloacal virus shedding, and interferon (IFN)-α, IFN-β and interleukin (IL)-22 expression in the trachea, lung, ileum and cecal tonsils was assessed. Higher virus shedding, and compromised type I IFNs and IL-22 expression was observed in ABX-D16 chickens compared to control, while PROB and FMT showed reduced virus shedding and restored IL-22 expression to levels comparable with undepleted chickens. In conclusion, commensal gut microbiota of chickens can modulate innate responses to influenza virus subtype H9N2 infection in chickens, and modulating the composition of the microbiome using probiotics- and/or FMT-based interventions might serve to promote a healthy community that confers protection against influenza virus infection in chickens.}, }
@article {pmid30181015, year = {2019}, author = {Wang, JW and Kuo, CH and Kuo, FC and Wang, YK and Hsu, WH and Yu, FJ and Hu, HM and Hsu, PI and Wang, JY and Wu, DC}, title = {Fecal microbiota transplantation: Review and update.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118 Suppl 1}, number = {}, pages = {S23-S31}, doi = {10.1016/j.jfma.2018.08.011}, pmid = {30181015}, issn = {0929-6646}, mesh = {Clostridioides difficile ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*adverse effects/*methods/trends ; Gastrointestinal Diseases/*therapy ; Humans ; Practice Guidelines as Topic ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a method to directly change the recipient's gut microbiota to normalize the composition and gain a therapeutic benefit. The history of FMT has been traced back to the 4th century and has been highly regarded since 2013, when the United States Food and Drug Administration approved FMT for treating recurrent and refractory Clostridium difficile infection. Since then, the range of FMT applications extended rapidly and broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Donor selection with questionnaire, interview, blood tests, and stool examinations should be strictly performed before FMT to reduce and prevent occurrence of any adverse events. Step-by-step cautious fecal and recipient preparation along with adequately choosing delivery methods based on individual clinical situations are key points of the FMT process. Although current evidence deems FMT as a generally safe therapeutic method with few adverse effects, the long-term outcomes of FMT have not been completely elucidated. Therefore, establishing periodicity and length of regular follow-up after FMT to monitor the clinical efficacy and long-term adverse events are other essential issues. In the future, we will look forward to personalized FMT for different patients and conditions according to varied hosts and diseases.}, }
@article {pmid30178725, year = {2018}, author = {Linfield, RY and Campeau, S and Injean, P and Gregson, A and Kaldas, F and Rubin, Z and Kim, T and Kunz, D and Chan, A and Lee, DJ and Humphries, RM and McKinnell, JA}, title = {Practical methods for effective vancomycin-resistant enterococci (VRE) surveillance: experience in a liver transplant surgical intensive care unit.}, journal = {Infection control and hospital epidemiology}, volume = {39}, number = {10}, pages = {1178-1182}, doi = {10.1017/ice.2018.178}, pmid = {30178725}, issn = {1559-6834}, mesh = {Feces/microbiology ; Female ; Gram-Positive Bacterial Infections/*diagnosis/epidemiology ; Humans ; *Intensive Care Units ; *Liver Transplantation ; Los Angeles/epidemiology ; Male ; Middle Aged ; Population Surveillance ; Prevalence ; Tertiary Care Centers ; *Vancomycin Resistance ; Vancomycin-Resistant Enterococci/*isolation &amp; purification ; }, abstract = {OBJECTIVE: We evaluated the utility of vancomycin-resistant Enterococcus (VRE) surveillance by varying 2 parameters: admission versus weekly surveillance and perirectal swabbing versus stool sampling.<br><br>DESIGN: Prospective, patient-level surveillance program of incident VRE colonization.<br><br>SETTING: Liver transplant surgical intensive care unit (SICU) of a tertiary-care referral medical center with a high prevalence of VRE.PatientsAll patients admitted to the SICU from June to August 2015.<br><br>METHODS: We conducted a point-prevalence estimate followed by admission and weekly surveillance by perirectal swabbing and/or stool sampling. Incident colonization was defined as a negative screen followed by positive surveillance. VRE was detected by culture on Remel Spectra VRE chromogenic agar. Microbiologically-confirmed VRE bloodstream infections (BSIs) were tracked for 2 months. Statistical analyses were calculated using the McNemar test, the Fisher exact test, the t test, and the &#x3c7;2 test.<br><br>RESULTS: In total, 91 patients underwent VRE surveillance testing. The point prevalence of VRE colonization was 60.9%; VRE prevalence on admission was 30.1%. Weekly surveillance identified an additional 7 of 28 patients (25.0%) with incident colonization. VRE BSIs were more common in VRE-colonized patients than in noncolonized patients (8 of 43 vs 2 of 48; P=.028). In a direct comparison, perirectal swabs were more sensitive than stool samples in detecting VRE (64 of 67 vs 56 of 67; P=.023). Compliance with perirectal swabbing was 89% (201 of 226) compared to 56% (127 of 226) for stool collection (P&#x2264;0.001).<br><br>CONCLUSIONS: We recommend weekly VRE surveillance over admission-only screening in high-burden units such as liver transplant SICUs. Perirectal swabs had greater collection compliance and sensitivity than stool samples, making them the preferred methodology. Further work may have implications for antimicrobial stewardship and infection control.}, }
@article {pmid30178233, year = {2018}, author = {Han, R and Ma, J and Li, H}, title = {Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota.}, journal = {Frontiers of medicine}, volume = {12}, number = {6}, pages = {645-657}, pmid = {30178233}, issn = {2095-0225}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Choline/metabolism ; *Dietary Supplements ; Energy Metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Insulin Resistance ; Intestines/*microbiology ; Non-alcoholic Fatty Liver Disease/*microbiology/therapy ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical "Two-hit" theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a "metabolic organ" that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD.}, }
@article {pmid30178042, year = {2018}, author = {Gupta, A and Cifu, AS and Khanna, S}, title = {Diagnosis and Treatment of Clostridium difficile Infection.}, journal = {JAMA}, volume = {320}, number = {10}, pages = {1031-1032}, doi = {10.1001/jama.2018.12194}, pmid = {30178042}, issn = {1538-3598}, mesh = {Adult ; Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Child ; Clostridioides difficile/genetics ; *Clostridium Infections/diagnosis/drug therapy/therapy ; *Fecal Microbiota Transplantation ; Fidaxomicin ; Humans ; Nucleic Acid Amplification Techniques ; *Practice Guidelines as Topic ; Recurrence ; Vancomycin/*therapeutic use ; }, }
@article {pmid30173851, year = {2018}, author = {Mullish, BH and Quraishi, MN and Segal, JP and McCune, VL and Baxter, M and Marsden, GL and Moore, D and Colville, A and Bhala, N and Iqbal, TH and Settle, C and Kontkowski, G and Hart, AL and Hawkey, PM and Williams, HR and Goldenberg, SD}, title = {The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.}, journal = {The Journal of hospital infection}, volume = {100 Suppl 1}, number = {}, pages = {S1-S31}, doi = {10.1016/j.jhin.2018.07.037}, pmid = {30173851}, issn = {1532-2939}, support = {EME/13/179/01/DH_/Department of Health/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Advisory Committees ; Anti-Infective Agents/therapeutic use ; Clostridium Infections/drug therapy/*therapy ; Communicable Diseases ; Evidence-Based Medicine ; *Fecal Microbiota Transplantation/methods/standards ; Feces ; Gastroenterology ; Humans ; Recurrence ; Severity of Illness Index ; Societies, Medical ; United Kingdom ; }, }
@article {pmid30173823, year = {2018}, author = {Flannigan, KL and Taylor, MR and Pereira, SK and Rodriguez-Arguello, J and Moffat, AW and Alston, L and Wang, X and Poon, KK and Beck, PL and Rioux, KP and Jonnalagadda, M and Chelikani, PK and Galipeau, HJ and Lewis, IA and Workentine, ML and Greenway, SC and Hirota, SA}, title = {An intact microbiota is required for the gastrointestinal toxicity of the immunosuppressant mycophenolate mofetil.}, journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, volume = {37}, number = {9}, pages = {1047-1059}, doi = {10.1016/j.healun.2018.05.002}, pmid = {30173823}, issn = {1557-3117}, support = {//CIHR/Canada ; }, mesh = {Animals ; Colon/drug effects/microbiology ; *Disease Models, Animal ; Gastrointestinal Tract/*drug effects/*microbiology ; Germ-Free Life ; High-Throughput Nucleotide Sequencing ; Humans ; Immunosuppressive Agents/therapeutic use/*toxicity ; Male ; Mice ; Mice, Inbred Strains ; Microbiota/*drug effects/immunology ; Mycophenolic Acid/therapeutic use/*toxicity ; Proteobacteria ; RNA, Ribosomal, 16S ; Sequence Analysis, RNA ; Weight Loss/drug effects ; }, abstract = {BACKGROUND: Mycophenolate mofetil (MMF) is commonly prescribed after transplantation and has major advantages over other immunosuppressive drugs, but frequent gastrointestinal (GI) side-effects limit its use. The mechanism(s) underlying MMF-related GI toxicity have yet to be elucidated.<br><br>METHODS: To investigate MMF-related GI toxicity, experimental mice were fed chow containing MMF (0.563%) and multiple indices of toxicity, including weight loss and colonic inflammation, were measured. Changes in intestinal microbial composition were detected using 16S rRNA Illumina sequencing, and downstream PICRUSt analysis was used to predict metagenomic pathways involved. Germ-free (GF) mice and mice treated with orally administered broad-spectrum antibiotics (ABX) were utilized to interrogate the importance of the microbiota in MMF-induced GI toxicity.<br><br>RESULTS: Mice treated with MMF exhibited significant weight loss, related to loss of body fat and muscle, and marked colonic inflammation. MMF exposure was associated with changes in gut microbial composition, as demonstrated by a loss of overall diversity, expansion of Proteobacteria (specifically Escherichia/Shigella), and enrichment of genes involved in lipopolysaccharide (LPS) biosynthesis, which paralleled increased levels of LPS in the feces and serum. MMF-related GI toxicity was dependent on the intestinal microbiota, as MMF did not induce weight loss or colonic inflammation in GF mice. Furthermore, ABX prevented and reversed MMF-induced weight loss and colonic inflammation.<br><br>CONCLUSIONS: An intact intestinal microbiota is required to initiate and sustain the GI toxicity of MMF. MMF treatment causes dynamic changes in the composition of the intestinal microbiota that may be a targetable driver of the GI side-effects of MMF.}, }
@article {pmid30173572, year = {2018}, author = {Ruiz, L and López, P and Suárez, A and Sánchez, B and Margolles, A}, title = {The role of gut microbiota in lupus: what we know in 2018?.}, journal = {Expert review of clinical immunology}, volume = {14}, number = {10}, pages = {787-792}, doi = {10.1080/1744666X.2018.1519395}, pmid = {30173572}, issn = {1744-8409}, mesh = {Dysbiosis/*immunology ; Gastrointestinal Microbiome/*immunology/physiology ; Humans ; Lupus Erythematosus, Systemic/*immunology/*microbiology ; }, abstract = {The role of the human intestinal microbiota in the maintenance of a healthy physiological condition, as well as its relation to the development of disease, remains to be clarified. Current evidence suggests that intestinal microbes could be involved in the initiation and amplification of autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus (SLE). Despite recent progress in understanding how these microbes influence the pathophysiology of lupus, studies are still limited. Areas covered: In this review, we have tried to summarize the most relevant findings that have contributed to our understanding of the links between the human intestinal microbiota and the development of lupus. We also describe the potential role of individual microbial players in the physiology of lupus, and how they can shape relevant immune responses. Expert commentary: Culture-independent techniques based on massive sequencing represent a powerful tool to unravel the biological activity of gut microbes. Current data demonstrates that, depending on the pattern of intestinal microorganisms or the presence of specific bacteria, different responses related to lupus physiology can be triggered. Fecal microbiota transplantation, live biotherapeutics, or dietary interventions targeting the microbiota will likely become a treatment for SLE.}, }
@article {pmid30173562, year = {2018}, author = {Delaune, V and Orci, LA and Lacotte, S and Peloso, A and Schrenzel, J and Lazarevic, V and Toso, C}, title = {Fecal microbiota transplantation: a promising strategy in preventing the progression of non-alcoholic steatohepatitis and improving the anti-cancer immune response.}, journal = {Expert opinion on biological therapy}, volume = {18}, number = {10}, pages = {1061-1071}, doi = {10.1080/14712598.2018.1518424}, pmid = {30173562}, issn = {1744-7682}, mesh = {Carcinoma, Hepatocellular/*immunology/microbiology/pathology/*prevention &amp; control ; Disease Progression ; Dysbiosis/complications/immunology/therapy ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/physiology ; Humans ; Immunity, Cellular/physiology ; Liver Neoplasms/*immunology/microbiology/pathology/*prevention &amp; control ; Non-alcoholic Fatty Liver Disease/complications/immunology/pathology/*therapy ; }, abstract = {INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has the potential to progress to hepatocellular carcinoma (HCC). However, limited therapies are currently available for the treatment of advanced HCC, and one must strive to search for novel strategies.<br><br>AREAS COVERED: We provide insight on current knowledge related to gut microbiota and NAFLD, summarize the sequence linking obesity to HCC and highlight gut dysbiosis in obesity and its consequences on the liver. We detail the impact of the gut microbiota on immune checkpoint inhibitors, and speculate on the role of fecal microbiota transplantation (FMT) in NAFLD and in improving anti-neoplastic immune response.<br><br>EXPERT OPINION: Manipulation of the gut microbiota seems promising in the secondary prevention of NAFLD/NASH and/or in potentiating anti-cancer immune response, notably by a global 'resetting' using FMT. However, the composition of a 'harmful' gut microbiome in HCC still needs to be characterized, and the impact of FMT on HCC growth needs to be assessed.}, }
@article {pmid30172346, year = {2018}, author = {Hum, RM and Deambrosis, D and Lum, SH and Davies, E and Bonney, D and Guiver, M and Turner, A and Wynn, RF and Hiwarkar, P}, title = {Molecular monitoring of adenovirus reactivation in faeces after haematopoietic stem-cell transplantation to predict systemic infection: a retrospective cohort study.}, journal = {The Lancet. Haematology}, volume = {5}, number = {9}, pages = {e422-e429}, doi = {10.1016/S2352-3026(18)30130-3}, pmid = {30172346}, issn = {2352-3026}, mesh = {Adenoviridae/*physiology ; Adenoviridae Infections/*diagnosis ; Child ; Child, Preschool ; Cohort Studies ; Feces/*virology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Infant ; Male ; Prognosis ; Retrospective Studies ; *Virus Activation ; }, abstract = {BACKGROUND: Faecal shedding of adenovirus following allogeneic haematopoietic stem-cell transplantation (HSCT) is an early sign of loss of immune control over adenovirus, but there is no consensus on the role of monitoring of faecal adenoviral load by serial testing. We investigated whether serial faecal PCR monitoring could predict the risk of adenoviraemia and survival outcomes after HSCT.<br><br>METHODS: We did a retrospective cohort study at the Royal Manchester Children's Hospital, Manchester, UK, of patients who had received their first allogeneic HSCT between Feb 1, 2003, and Sept 1, 2016, and adenovirus infection recorded in their medical records. We excluded patients who had received second or third transplants or autologous HSCT transplants. We obtained characteristics of patients and transplants, including mortality and adenoviral reactivation, from medical records and the hospital database. All patients had blood samples tested weekly for adenovirus by PCR until immunosuppression was stopped and CD3 T-cell count recovered to greater than 0&#xb7;3&#x2008;&#xd7;&#x2008;10[9]/L. Faecal PCR was done before transplantation in all patients, and after transplantation in patients who had diarrhoea, at the onset of symptoms and weekly thereafter until diarrhoea resolved. We analysed all samples available before and after HSCT. We did subgroup analyses for patients undergoing HSCT for cancer versus non-malignant conditions. We also assessed whether 5 log10 copies per g faeces was a suitable predictive threshold for adenoviraemia.<br><br>FINDINGS: We included 341 patients who had undergone a first allogeneic HSCT (median age 4&#xb7;6 years, IQR 1&#xb7;5-8&#xb7;0, range 0-20&#xb7;0). After HSCT, PCR was done in 4116 faecal samples from 293 (86%) patients who had diarrhoea and in 10&#x2008;649 blood samples from 341 patients. Follow-up ended on July 14, 2017. 173 (59%) of 293 patients had adenovirus in faecal samples and 63 (18%) of 341 had adenovirus in blood samples. Maximum faecal viral load before adenoviraemia correlated significantly with maximum blood viral load (r=0&#xb7;51, 95% CI 0&#xb7;38-0&#xb7;61, p<0&#xb7;0001). Faecal adenoviral viral load greater than 5 log10 copies per g faeces was predictive of adenoviraemia (odds ratio 10&#xb7;2, 95% CI 4&#xb7;9-21&#xb7;6, p<0&#xb7;0001) with sensitivity 75&#xb7;9% and specificity 74&#xb7;8%. These values were increased further in patients with cancer, to 86&#xb7;4% and 87&#xb7;5%, respectively. Among the 28 patients who had positive faecal and blood samples and who had undergone serial faecal PCR monitoring after HSCT, the median time between reaching the faecal viral load threshold and onset of adenoviraemia was 8&#xb7;0 days (IQR 2&#xb7;3-21&#xb7;8, 95% CI 4&#xb7;0-16&#xb7;0). Non-relapse mortality was not associated with adenovirus reactivation in faeces alone (9&#xb7;2%, 95% CI 5&#xb7;4-14&#xb7;3 in patients without reactivation vs 7&#xb7;8%, 3&#xb7;8-13&#xb7;7 in those with positive faeces only), but was significantly increased in patients who developed adenoviraemia (27&#xb7;0%, 95% CI 16&#xb7;7-38&#xb7;4, p<0&#xb7;0001).<br><br>INTERPRETATION: We identified a threshold faecal viral load that can predict the risk of adenoviraemia. Our findings support proliferation of adenovirus in the gastrointestinal tract before viraemia develops. Faecal PCR is suitable for early detection of children and young adults at risk of adenoviraemia, and its use might help reduce non-relapse mortality in allogeneic HSCT recipients.<br><br>FUNDING: None.}, }
@article {pmid30171064, year = {2019}, author = {Tito, RY and Chaffron, S and Caenepeel, C and Lima-Mendez, G and Wang, J and Vieira-Silva, S and Falony, G and Hildebrand, F and Darzi, Y and Rymenans, L and Verspecht, C and Bork, P and Vermeire, S and Joossens, M and Raes, J}, title = {Population-level analysis of Blastocystis subtype prevalence and variation in the human gut microbiota.}, journal = {Gut}, volume = {68}, number = {7}, pages = {1180-1189}, pmid = {30171064}, issn = {1468-3288}, mesh = {Adult ; Aged ; Belgium ; Blastocystis/*isolation &amp; purification ; Case-Control Studies ; Cohort Studies ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Male ; Middle Aged ; Prevalence ; }, abstract = {OBJECTIVE: Human gut microbiome studies are mainly bacteria- and archaea-oriented, overlooking the presence of single-cell eukaryotes such as Blastocystis, an enteric stramenopiles with worldwide distribution. Here, we surveyed the prevalence and subtype variation of Blastocystis in faecal samples collected as part of the Flemish Gut Flora Project (FGFP), a Western population cohort. We assessed potential links between Blastocystis subtypes and identified microbiota-host covariates and quantified microbiota differentiation relative to subtype abundances.<br><br>DESIGN: We profiled stool samples from 616 healthy individuals from the FGFP cohort as well as 107 patients with IBD using amplicon sequencing targeting the V4 variable region of the 16S rRNA and 18S rRNA genes. We evaluated associations of Blastocystis, and their subtypes, with host parameters, diversity and composition of bacterial and archaeal communities.<br><br>RESULTS: Blastocystis prevalence in the non-clinical population cohort was 30% compared with 4% among Flemish patients with IBD. Within the FGFP cohort, out of 69 previously identified gut microbiota covariates, only age was associated with Blastocystis subtype carrier status. In contrast, a strong association between microbiota community composition and Blastocystis subtypes was observed, with effect sizes larger than that of host covariates. Microbial richness and diversity were linked to both Blastocystis prevalence and subtype variation. All Blastocystis subtypes detected in this cohort were found to be less prevalent in Bacteroides enterotyped samples. Interestingly, Blastocystis subtypes 3 and 4 were inversely correlated with Akkermansia, suggesting differential associations of subtypes with host health.<br><br>CONCLUSIONS: These results emphasise the role of Blastocystis as a common constituent of the healthy gut microbiota. We show its prevalence is reduced in patients with active IBD and demonstrate that subtype characterisation is essential for assessing the relationship between Blastocystis, microbiota profile and host health. These findings have direct clinical applications, especially in donor selection for faecal transplantation.}, }
@article {pmid30165051, year = {2018}, author = {Jodal, HC and Løberg, M and Holme, &#xd8; and Adami, HO and Bretthauer, M and Emilsson, L and Ransohoff, DF and Hoff, G and Kalager, M}, title = {Mortality From Postscreening (Interval) Colorectal Cancers Is Comparable to That From Cancer in Unscreened Patients-A Randomized Sigmoidoscopy Trial.}, journal = {Gastroenterology}, volume = {155}, number = {6}, pages = {1787-1794.e3}, doi = {10.1053/j.gastro.2018.08.035}, pmid = {30165051}, issn = {1528-0012}, mesh = {Cause of Death ; Colorectal Neoplasms/diagnosis/*mortality ; Early Detection of Cancer/methods/*mortality ; Female ; Humans ; Male ; Middle Aged ; Norway ; Proportional Hazards Models ; Rectal Neoplasms/diagnosis/mortality ; Regression Analysis ; Sigmoid Neoplasms/diagnosis/mortality ; Sigmoidoscopy/methods/*mortality ; Time Factors ; }, abstract = {BACKGROUND &amp; AIMS: Endoscopic screening for colorectal cancer (CRC) is performed at longer time intervals than the fecal occult blood test or screenings for breast or prostate cancer. This causes concerns about interval cancers, which have been proposed to progress more rapidly. We compared outcomes of patients with interval CRCs after sigmoidoscopy screening vs outcomes of patients with CRC who had not been screened.<br><br>METHODS: We performed a secondary analysis of a randomized sigmoidoscopy screening trial in Norway with 98,684 participants (age range, 50-64 years) who were randomly assigned to groups that were (n&#xa0;= 20,552) or were not (n&#xa0;= 78,126) invited for sigmoidoscopy screening from 1999 through 2001; participants were followed up for a median 14.8 years. We compared CRC mortality and all-cause mortality between individuals who underwent screening and were diagnosed with CRC 30 days or longer after screening (interval cancer group, n&#xa0;= 163) and individuals diagnosed with CRC in the nonscreened group (controls, n&#xa0;= 1740). All CRCs in the control group were identified when they developed symptoms (clinically detected CRCs). Analyses were stratified by cancer site. We used Cox regression to estimate hazard ratio (HRs), adjusted for age and sex.<br><br>RESULTS: Over the follow-up period, 43 individuals in the interval cancer group died from CRC; among controls, 525 died from CRC. CRC mortality (adjusted HR, 0.98; 95% confidence interval, 0.72-1.35; P&#xa0;= .92), rectosigmoid cancer mortality (adjusted HR, 1.10; 95% confidence interval, 0.63-1.92; P&#xa0;= .74), and all-cause mortality (adjusted HR, 0.99; 95% confidence interval, 0.76-1.27; P&#xa0;= .91) did not differ significantly between the interval cancer group and controls.<br><br>CONCLUSIONS: In this randomized sigmoidoscopy screening trial, mortality did not differ significantly between individuals with interval CRCs and unscreened patients with clinically detected CRCs. ClinicalTrials.gov identifier: NCT00119912.}, }
@article {pmid30158649, year = {2018}, author = {Wang, S and Huang, M and You, X and Zhao, J and Chen, L and Wang, L and Luo, Y and Chen, Y}, title = {Gut microbiota mediates the anti-obesity effect of calorie restriction in mice.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {13037}, pmid = {30158649}, issn = {2045-2322}, support = {2016YFA0500103//Ministry of Science and Technology of the People&apos;s Republic of China (Chinese Ministry of Science and Technology)/International ; }, mesh = {Animals ; *Caloric Restriction ; *Gastrointestinal Microbiome ; Metabolism ; Mice ; *Weight Loss ; }, abstract = {Calorie restriction (CR) extends lifespan and elicits numerous effects beneficial to health and metabolism in various model organisms, but the underlying mechanisms are not completely understood. Gut microbiota has been reported to be associated with the beneficial effects of CR; however, it is unknown whether these effects of CR are causally mediated by gut microbiota. In this study, we employed an antibiotic-induced microbiota-depleted mouse model to investigate the functional role of gut microbiota in CR. Depletion of gut microbiota rendered mice resistant to CR-induced loss of body weight, accompanied by the increase in fat mass, the reduction in lean mass and the decline in metabolic rate. Depletion of gut microbiota led to increases in fasting blood glucose and cholesterol levels independent of CR. A few metabolism-modulating hormones including leptin and insulin were altered by CR and/or gut microbiota depletion. In addition, CR altered the composition of gut microbiota with significant increases in major probiotic genera such as Lactobacillus and Bifidobacterium, together with the decrease of Helicobacter. In addition, we performed fecal microbiota transplantation in mice fed with high-fat diet. Mice with transferred microbiota from calorie-restricted mice resisted high fat diet-induced obesity and exhibited metabolic improvement such as alleviated hepatic lipid accumulation. Collectively, these data indicate that CR-induced metabolic improvement especially in body weight reduction is mediated by intestinal microbiota to a certain extent.}, }
@article {pmid30158252, year = {2019}, author = {Enck, P}, title = {Primum non nocere: is faecal microbiota transplantation doing harm to patients with IBS?.}, journal = {Gut}, volume = {68}, number = {9}, pages = {1722-1723}, doi = {10.1136/gutjnl-2018-317277}, pmid = {30158252}, issn = {1468-3288}, mesh = {Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome ; }, }
@article {pmid30157944, year = {2018}, author = {Mohamed, NS and Siddig, EE and Mohamed, MA and Alzein, BA and Osman, HHS and Tanyous, EE and Elamin, BK and Edris, AMM}, title = {Enteroparasitosis infections among renal transplant recipients in Khartoum state, Sudan 2012-2013.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {621}, pmid = {30157944}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Child ; Feces ; Female ; Humans ; Intestinal Diseases, Parasitic/epidemiology/*etiology ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Parasites ; Prevalence ; Sudan/epidemiology ; Young Adult ; }, abstract = {OBJECTIVES: Renal transplantation procedure markedly increased over the past few decades. The risk of harboring parasitic diseases may affect transplant recipients during life expectancy. We aimed in this study to determine the enteroparasitosis frequency among renal transplant recipients in Khartoum state, Sudan. A case-control hospital-based study performed between November 2012 and May 2013, on 300 renal transplant recipients attending Sudanese Kidney Association hospital in Khartoum state, Sudan, along with 300 normal healthy individuals matching the case in age and sex. Stool samples were collected for parasitological studies.<br><br>RESULTS: Out of the 300 renal transplant recipients: 242 (80.7%) were males mean age 43&#x2009;&#xb1;&#x2009;11.28 and 58 (19.3%) were females mean age 41&#x2009;&#xb1;&#x2009;13.41. Intestinal parasitic infection was observed in 118 participants and the overall frequency was 19.7%; of which 64 were cases (21.3%) and 54 (18.0%) were controls. Eight different species of intestinal parasites were identified; Entamoeba histolytica/dispar (7.5%), Entamoeba coli (6.5%), Giardia lambelia (3.2%), Cryptosporidium parvum (1.2%), Ascaris lumbricoides (0.6%), Enterobius vermicularis (0.3%), (0.2%) for each of Strongyloides stercoralis and Hymenolepis nana.}, }
@article {pmid30155958, year = {2018}, author = {Barfuss, S and Knackstedt, ED and Jensen, K and Molina, K and Lal, A}, title = {Cardiac allograft vasculopathy following fecal microbiota transplantation for recurrent C. difficile infection.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {20}, number = {6}, pages = {e12983}, doi = {10.1111/tid.12983}, pmid = {30155958}, issn = {1399-3062}, mesh = {Allografts/*blood supply/immunology ; Anti-Bacterial Agents/therapeutic use ; Child, Preschool ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Coronary Vessels/immunology ; Fecal Microbiota Transplantation/*adverse effects ; Graft Rejection/*immunology/surgery ; Heart Transplantation/*adverse effects ; Humans ; Male ; Myocardium/immunology ; Recurrence ; Reoperation ; Vascular Diseases/*immunology/surgery ; }, abstract = {We report the case of a 3-year-old male who developed recurrent Clostridium difficile infection after receiving an orthotopic heart transplant. Despite multiple courses of antibiotics, C. difficile infection was persistent and he underwent a fecal microbiota transplant. The patient responded with resolution of his diarrhea. However, within 2 months he developed severe mixed rejection with high circulating donor-specific antibodies and significant coronary vasculopathy. Organ dysfunction led to the need for re-transplantation. The patient's postoperative course has since been complicated by pneumatosis intestinalis and recurrent C. difficile infection.}, }
@article {pmid30154767, year = {2018}, author = {Kho, ZY and Lal, SK}, title = {The Human Gut Microbiome - A Potential Controller of Wellness and Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1835}, pmid = {30154767}, issn = {1664-302X}, abstract = {Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.}, }
@article {pmid30154172, year = {2018}, author = {Mullish, BH and Quraishi, MN and Segal, JP and McCune, VL and Baxter, M and Marsden, GL and Moore, DJ and Colville, A and Bhala, N and Iqbal, TH and Settle, C and Kontkowski, G and Hart, AL and Hawkey, PM and Goldenberg, SD and Williams, HRT}, title = {The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.}, journal = {Gut}, volume = {67}, number = {11}, pages = {1920-1941}, doi = {10.1136/gutjnl-2018-316818}, pmid = {30154172}, issn = {1468-3288}, support = {MR/R000875/1//Medical Research Council/United Kingdom ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/drug effects ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastroenterology/organization &amp; administration ; Gastrointestinal Tract/*microbiology ; Humans ; Recurrence ; Societies, Medical ; Tissue Donors ; United Kingdom ; }, abstract = {Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.}, }
@article {pmid30153805, year = {2018}, author = {Brown, JR and Flemer, B and Joyce, SA and Zulquernain, A and Sheehan, D and Shanahan, F and O'Toole, PW}, title = {Changes in microbiota composition, bile and fatty acid metabolism, in successful faecal microbiota transplantation for Clostridioides difficile infection.}, journal = {BMC gastroenterology}, volume = {18}, number = {1}, pages = {131}, pmid = {30153805}, issn = {1471-230X}, support = {(SFI/12/RC/2273)//Science Foundation Ireland/Ireland ; SFI/12/RC/2273//Science Foundation Ireland/Ireland ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bile Acids and Salts/metabolism ; *Clostridioides difficile ; Clostridium Infections/metabolism/*microbiology/*therapy ; Fatty Acids, Volatile/metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Recurrence ; Young Adult ; }, abstract = {BACKGROUND: Alteration of the gut microbiota by repeated antibiotic treatment increases susceptibility to Clostridioides difficile infection. Faecal microbiota transplantation from donors with a normal microbiota effectively treats C. difficile infection.<br><br>METHODS: The study involved 10 patients with recurrent C. difficile infection, nine of whom received transplants from individual donors and one who received a donor unit from a stool bank (OpenBiome).<br><br>RESULTS: All individuals demonstrated enduring post-transplant resolution of C. difficile- associated diarrhoea. Faecal microbiota diversity of recipients significantly increased, and the composition of the microbiota resembled that of the donor. Patients with C. difficile infection exhibited significantly lower faecal levels of secondary/ bile acids and higher levels of primary bile acids. Levels of secondary bile acids were restored in all transplant recipients, but to a lower degree with the OpenBiome transplant. The abundance increased of bacterial genera known from previous studies to confer resistance to growth and germination of C. difficile. These were significantly negatively associated with primary bile acid levels and positively related with secondary bile acid levels. Although reduced levels of the short chain fatty acids, butyrate, propionate and acetate, have been previously reported, here we report elevations in SCFA, pyruvic and lactic fatty acids, saturated, &#x3c9;-6, monounsaturated, &#x3c9;-3 and &#x3c9;-6 polyunsaturated fatty acids (PUFA) in C. difficile infection. This potentially indicates one or a combination of increased dietary FA intake, microbial modification of FAs or epithelial cell damage and inflammatory cell recruitment. No reversion to donor FA profile occurred post-FMT but &#x3c9;-3 to &#x3c9;-6 PUFA ratios were altered in the direction of the donor. Archaeal metabolism genes were found in some samples post FMT.<br><br>CONCLUSION: A consistent metabolic signature was identified in the post-transplant microbiota, with reduced primary bile acids and substantial restoration of secondary bile acid production capacity. Total FA levels were unchanged but the ratio of inflammatory to non-inflammatory FAs decreased.}, }
@article {pmid30150145, year = {2018}, author = {Zhang, X and Zhao, S and Song, X and Jia, J and Zhang, Z and Zhou, H and Fu, H and Cui, H and Hu, S and Fang, M and Liu, X and Bian, Y}, title = {Inhibition effect of glycyrrhiza polysaccharide (GCP) on tumor growth through regulation of the gut microbiota composition.}, journal = {Journal of pharmacological sciences}, volume = {137}, number = {4}, pages = {324-332}, doi = {10.1016/j.jphs.2018.03.006}, pmid = {30150145}, issn = {1347-8648}, mesh = {Animals ; *Antineoplastic Agents, Phytogenic ; Cell Line, Tumor ; Cell Transformation, Neoplastic/*drug effects ; Colonic Neoplasms/*drug therapy/*pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects/*physiology ; Glycyrrhiza uralensis/*chemistry ; Male ; Mice, Inbred BALB C ; *Phytotherapy ; Polysaccharides/*isolation &amp; purification/*pharmacology ; }, abstract = {Glycyrrhiza Uralensis Polysaccharide (GCP), as a macromolecular polysaccharide extracted from the Traditional Chinese Medicine (TCM) - Licorice has been proved to inhibit tumor growth in vitro and in vivo; however, the specific anti-tumor mechanism of GCP needs to be further investigated. In this study, we explore the anti-tumor mechanism of GCP from the angle of gut microbiota. Colon carcinoma cells (CT-26) were used to set up a tumor-bearing mouse model. After 14 days of GCP treatment, the weights of tumors were significantly reduced. In addition, HE staining of tissue sections reflected that GCP could effectively inhibit tumor metastasis. 16SrRNA high-throughput sequencing of fecal samples showed a significant change between the model group and GCP group in the composition of gut microbiota. Subsequently, gut microbiota depletion and fecal transplantation experiments further confirmed the relationship between the anti-tumor effects of GCP and gut microbiota. Following depletion of gut microbiota, GCP cannot inhibit tumor growth. Fecal transplantation experiments found that transplanting the feces of GCP-treated mice, to a certain extent, could inhibit tumor growth and metastasis. These results indicate that Glycyrrhiza Polysaccharides exert anti-tumor effects by affecting gut microbiota composition.}, }
@article {pmid30148975, year = {2018}, author = {Tampaki, EC and Tampakis, A and Posabella, A and Patsouris, E and Kontzoglou, K and Kouraklis, G}, title = {Current clostridium difficile treatments: Lessons that need to be learned from the clinical trials.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {14}, number = {12}, pages = {2874-2875}, pmid = {30148975}, issn = {2164-554X}, abstract = {Clostridium difficile infection (CDI) is the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. Judging from the clinical trials on drugs used in CDIs, no approved treatment for recurrences exists, possibly indicating that a combination of treatment approaches are mandatory especially in severe infections, with current studies not being fully representative. Among the new strategies researched intensively fidaxomicin is presented, which demonstrates reduced CDI recurrences. Moreover, biotherapeutic strategies, mainly fecal microbiota transplantation but also competitive inhibition with non-toxigenic strains of C. difficile, and finally monoclonal antibodies against C. difficile toxins which offer protection against recurrences. Careful interpretation of the results based on lessons learned from previous trials conducted seems crucial. Questions are raised regarding how the results of future studies regarding new strategies researched will be managed and interpreted especially with regard to recurrence management as relevant data must be monitored for at least 30 days after end of treatment.}, }
@article {pmid30146910, year = {2018}, author = {Balakrishnan, B and Taneja, V}, title = {Microbial modulation of the gut microbiome for treating autoimmune diseases.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {12}, number = {10}, pages = {985-996}, doi = {10.1080/17474124.2018.1517044}, pmid = {30146910}, issn = {1747-4132}, mesh = {Anti-Bacterial Agents/therapeutic use ; Autoimmune Diseases/microbiology/*therapy ; Bacteroides fragilis ; Bacteroides thetaiotaomicron ; Diet ; Faecalibacterium prausnitzii ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; Humans ; Microorganisms, Genetically-Modified ; Prevotella ; Probiotics/pharmacology/*therapeutic use ; Verrucomicrobia ; }, abstract = {Many studies have shown the relationship between autoimmune diseases and the gut microbiome in humans: those with autoimmune conditions display gut microbiome dysbiosis. The big question that needs to be addressed is if restoring eubiosis of the gut microbiota can help suppress the autoimmune condition by activating various immune regulatory mechanisms. Inducing these self-healing mechanisms should prolong good health in affected individuals. Area covered: Here, we review the available clinical and preclinical studies that have used selective bacteria for modulating gut microbiota for treating autoimmune diseases. The potential bacterial candidates and their mechanism of action in treating autoimmune diseases will be discussed. We searched for genetically modified and potential probiotics for diseases and discuss the most likely candidates. Expert commentary: To achieve eubiosis, manipulation of the gut microbiota must occur in some form. Several approaches for modulating gut microbiota include prebiotic diets, antimicrobial interventions, fecal microbiota transplants, and selective probiotics. One novel approach showing promising results is the use of selective bacterial candidates to modulate microbial composition. Use of single microbe for treatment has an advantage as compared to multi-species as microbes grow at different rates and if needed, a single microbe is easy to target.}, }
@article {pmid30146033, year = {2018}, author = {Pouch, SM and Friedman-Moraco, RJ}, title = {Prevention and Treatment of Clostridium difficile-Associated Diarrhea in Solid Organ Transplant Recipients.}, journal = {Infectious disease clinics of North America}, volume = {32}, number = {3}, pages = {733-748}, doi = {10.1016/j.idc.2018.05.001}, pmid = {30146033}, issn = {1557-9824}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/*complications/drug therapy/microbiology ; Diarrhea/complications/*microbiology ; Fecal Microbiota Transplantation ; Humans ; Organ Transplantation/*adverse effects ; Postoperative Complications/drug therapy/*microbiology ; }, abstract = {Clostridium difficile infection is a significant cause of morbidity and mortality in solid organ transplant recipients. Risk factors in this population include frequent hospitalizations, receipt of immunosuppressive agents, and intestinal dysbiosis triggered by several factors, including exposure to broad-spectrum antimicrobials. The incidence and potential for significant adverse outcomes among solid organ transplant recipients with C difficile infection highlight the evolving need for strategic C difficile infection risk factor modification and novel approaches to disease management in this patient population. This review focuses on current concepts related to the prevention and treatment of C difficile infection in solid organ transplant recipients.}, }
@article {pmid30140609, year = {2018}, author = {Dias, C and Pipa, S and Duarte-Ribeiro, F and Mota, M}, title = {Fecal microbiota transplantation as a potential way to eradicate multiresistant microorganisms.}, journal = {IDCases}, volume = {13}, number = {}, pages = {e00432}, pmid = {30140609}, issn = {2214-2509}, abstract = {Multiresistant microorganism infection often can produce a life-threatening situation. We report two cases in which fecal microbiota transplantation used for the treatment of recurrent Clostridium difficile infection were effective in eradicating colonization by carbapenemase-producing Enterobacteriaceae. The presented cases illustrate the potential benefit of fecal microbiota transplantation in resolution of asymptomatic carrier states of multiresistant microorganisms, suggesting the need for further investigations with a view to their applicability in this area.}, }
@article {pmid30138161, year = {2018}, author = {Khan, MY and Dirweesh, A and Khurshid, T and Siddiqui, WJ}, title = {Comparing fecal microbiota transplantation to standard-of-care treatment for recurrent Clostridium difficile infection: a systematic review and meta-analysis.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {30}, number = {11}, pages = {1309-1317}, doi = {10.1097/MEG.0000000000001243}, pmid = {30138161}, issn = {1473-5687}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/diagnosis/microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: The use of fecal microbiota transplantation (FMT) as a treatment option for recurrent Clostridium difficile infection (rCDI) is well established. Various studies have used different forms and administration routes for FMT. We performed a systemic review and meta-analysis to update the clinical knowledge about different FMT modalities for curing rCDI compared with medical treatment (MT).<br><br>PATIENTS AND METHODS: We searched PubMed and Medline from inception through 10 May 2018 for randomized control trials (RCTs) comparing FMT (fresh or frozen) versus MT. We used Cochrane Collaboration's Risk of Bias tool to assess bias in the RCTs. We estimated odds ratio (OR) with 95% confidence interval (CI) for each outcome using a random effects model. P values of less than 0.05 were considered significant.<br><br>RESULTS: We included seven RCTs comprising a total of 543 patients with recurrent CDI. There was a nonsignificant trend toward resolution of diarrhea following a single fresh FMT infusion compared with frozen FMT and MT (OR=2.45, 95% CI=0.78-7.71, P=0.12, I=69%). Subgroup analysis of fresh FMT vs. frozen FMT showed no difference between the two groups (OR=2.13, 95% CI=0.22-20.41, P=0.51, I=61%). Frozen FMT infusion through upper route versus lower route showed no difference (OR=0.62, 95% CI=0.15-2.54, P=0.51, I=0%). There was a nonsignificant trend favoring multiple treatments with FMT versus multiple courses of MT (OR=3.68, 95% CI=0.74-18.22, P=0.11, I=0%).<br><br>CONCLUSION: FMT is a promising treatment modality for rCDI compared with MT alone. Different forms and routes of FMT administration seem to be equally efficacious. In future, more well-designed RCTs directed at homogenous FMT preparation and delivery methods are required to validate these findings.}, }
@article {pmid30131654, year = {2018}, author = {Quaglia, NC and Dambrosio, A}, title = {Helicobacter pylori: A foodborne pathogen?.}, journal = {World journal of gastroenterology}, volume = {24}, number = {31}, pages = {3472-3487}, pmid = {30131654}, issn = {2219-2840}, mesh = {Animals ; Chronic Disease/prevention &amp; control ; Drinking Water/microbiology ; Fast Foods/microbiology ; Feces/microbiology ; Food Microbiology/*methods ; Foodborne Diseases/*microbiology/prevention &amp; control ; Gastrointestinal Diseases/*microbiology/prevention &amp; control ; Helicobacter Infections/microbiology/prevention &amp; control/*transmission ; Helicobacter pylori/isolation &amp; purification/*pathogenicity ; Humans ; Meat/microbiology ; Seawater/microbiology ; Vegetables/microbiology ; }, abstract = {Helicobacter pylori (H. pylori) is an organism that is widespread in the human population and is sometimes responsible for some of the most common chronic clinical disorders of the upper gastrointestinal tract in humans, such as chronic-active gastritis, duodenal and gastric ulcer disease, low-grade B-cell mucosa associated lymphoid tissue lymphoma of the stomach, and gastric adenocarcinoma, which is the third leading cause of cancer death worldwide. The routes of infection have not yet been firmly established, and different routes of transmission have been suggested, although the most commonly accepted hypothesis is that infection takes place through the faecal-oral route and that contaminated water and foods might play an important role in transmission of the microorganism to humans. Furthermore, several authors have considered H. pylori to be a foodborne pathogen because of some of its microbiological and epidemiological characteristics. H. pylori has been detected in drinking water, seawater, vegetables and foods of animal origin. H. pylori survives in complex foodstuffs such as milk, vegetables and ready-to-eat foods. This review article presents an overview of the present knowledge on the microbiological aspects in terms of phenotypic characteristics and growth requirements of H. pylori, focusing on the potential role that foodstuffs and water may play in the transmission of the pathogen to humans and the methods successfully used for the detection of this microorganism in foodstuffs and water.}, }
@article {pmid30126889, year = {2019}, author = {Milliken, EJT}, title = {Fifty years of faecal microbiota transplant in Central Australia.}, journal = {Gut}, volume = {68}, number = {8}, pages = {1536}, doi = {10.1136/gutjnl-2018-317235}, pmid = {30126889}, issn = {1468-3288}, mesh = {Australia ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Microbiota ; }, }
@article {pmid30124831, year = {2018}, author = {Ishikawa, D and Sasaki, T and Takahashi, M and Kuwahara-Arai, K and Haga, K and Ito, S and Okahara, K and Nakajima, A and Shibuya, T and Osada, T and Hiramatsu, K and Watanabe, S and Nagahara, A}, title = {The Microbial Composition of Bacteroidetes Species in Ulcerative Colitis Is Effectively Improved by Combination Therapy With Fecal Microbiota Transplantation and Antibiotics.}, journal = {Inflammatory bowel diseases}, volume = {24}, number = {12}, pages = {2590-2598}, doi = {10.1093/ibd/izy266}, pmid = {30124831}, issn = {1536-4844}, mesh = {Amoxicillin/administration &amp; dosage ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacteroidetes/*classification ; Colitis, Ulcerative/microbiology/*therapy ; Combined Modality Therapy ; Dysbiosis/etiology/therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Fosfomycin/administration &amp; dosage ; *Gastrointestinal Microbiome ; Humans ; Metronidazole/administration &amp; dosage ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: We previously reported that fresh fecal microbiota transplantation (FMT) after triple-antibiotic therapy (amoxicillin, fosfomycin, and metronidazole [AFM]; A-FMT) synergistically contributed to the recovery of phylum Bacteroidetes composition associated with the endoscopic severity and treatment efficacy of ulcerative colitis (UC). Here, we performed further microbial analyses using a higher-resolution method to identify the key bacterial species in UC and determine whether viable Bacteroidetes species from donor feces were successfully colonized by A-FMT.<br><br>METHODS: The taxonomic composition of Bacteroidetes in 25 healthy donors and 27 UC patients at baseline was compared at the species level using a heat-shock protein (hsp) 60-based microbiome method. Microbiota alterations before and after treatment of UC patients were also analyzed in 24 cases (n = 17 A-FMT; n = 3 mono-AFM; n = 4 mono-FMT).<br><br>RESULTS: We found species-level dysbiosis within the phylum Bacteroidetes in UC samples, which was associated with reduced species diversity, resulting from hyperproliferation and hypoproliferation of particular species. Moreover, in responders treated with A-FMT, diversity was significantly recovered at 4 weeks after a fresh round of FMT, after which high degrees of similarity in Bacteroidetes species composition among recipients and donors were observed.<br><br>CONCLUSIONS: A-FMT alleviated intestinal dysbiosis, which is caused by the loss of Bacteroidetes species diversity in patients with UC. Eradication of dysbiotic indigenous Bacteroidetes species by AFM pretreatment might promote the colonization of viable Bacteroidetes cells, thereby improving the intestinal microbiota dysbiosis induced by UC. Our findings serve as a basis for further investigations into the mechanisms of FMT.}, }
@article {pmid30123820, year = {2018}, author = {Williamson, IA and Arnold, JW and Samsa, LA and Gaynor, L and DiSalvo, M and Cocchiaro, JL and Carroll, I and Azcarate-Peril, MA and Rawls, JF and Allbritton, NL and Magness, ST}, title = {A High-Throughput Organoid Microinjection Platform to Study Gastrointestinal Microbiota and Luminal Physiology.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {6}, number = {3}, pages = {301-319}, pmid = {30123820}, issn = {2352-345X}, support = {UL1 TR001111/TR/NCATS NIH HHS/United States ; R01 DK091427/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; R01 DK081426/DK/NIDDK NIH HHS/United States ; R01 DK109559/DK/NIDDK NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; UL1 TR001117/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Bifidobacterium adolescentis/genetics/growth &amp; development/isolation &amp; purification ; Colon/anatomy &amp; histology/*cytology ; Escherichia coli/genetics/growth &amp; development ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*physiology ; Humans ; Male ; Mice ; Microinjections/*methods ; Organoids/anatomy &amp; histology/*cytology ; Single-Cell Analysis ; Video Recording ; Yersinia pseudotuberculosis/genetics/growth &amp; development ; }, abstract = {BACKGROUND &amp; AIMS: The human gut microbiota is becoming increasingly recognized as a key factor in homeostasis and disease. The lack of physiologically relevant in vitro models to investigate host-microbe interactions is considered a substantial bottleneck for microbiota research. Organoids represent an attractive model system because they are derived from primary tissues and embody key properties of the native gut lumen; however, access to the organoid lumen for experimental perturbation is challenging. Here, we report the development and validation of a high-throughput organoid microinjection system for cargo delivery to the organoid lumen and high-content sampling.<br><br>METHODS: A microinjection platform was engineered using off-the-shelf and 3-dimensional printed components. Microinjection needles were modified for vertical trajectories and reproducible injection volumes. Computer vision (CVis) and microfabricated CellRaft Arrays (Cell Microsystems, Research Triangle Park, NC) were used to increase throughput and enable high-content sampling of mock bacterial communities. Modeling preformed using the COMSOL Multiphysics platform predicted a hypoxic luminal environment that was functionally validated by transplantation of fecal-derived microbial communities and monocultures of a nonsporulating anaerobe.<br><br>RESULTS: CVis identified and logged locations of organoids suitable for injection. Reproducible loads of 0.2 nL could be&#xa0;microinjected into the organoid lumen at approximately 90 organoids/h. CVis analyzed and confirmed retention of injected cargos in approximately 500 organoids over 18 hours and showed the requirement to normalize for organoid growth for accurate assessment of barrier function. CVis&#xa0;analyzed growth dynamics of a mock community of green fluorescent protein- or Discosoma sp. red fluorescent protein-expressing bacteria, which grew within the organoid lumen even in the presence of antibiotics to control media contamination. Complex microbiota communities from fecal samples survived and grew in the colonoid lumen without appreciable changes in&#xa0;complexity.<br><br>CONCLUSIONS: High-throughput microinjection into organoids represents a next-generation in&#xa0;vitro approach to investigate gastrointestinal luminal physiology and the gastrointestinal microbiota.}, }
@article {pmid30123315, year = {2018}, author = {Pisano, M and Zorcolo, L and Merli, C and Cimbanassi, S and Poiasina, E and Ceresoli, M and Agresta, F and Allievi, N and Bellanova, G and Coccolini, F and Coy, C and Fugazzola, P and Martinez, CA and Montori, G and Paolillo, C and Penachim, TJ and Pereira, B and Reis, T and Restivo, A and Rezende-Neto, J and Sartelli, M and Valentino, M and Abu-Zidan, FM and Ashkenazi, I and Bala, M and Chiara, O and De' Angelis, N and Deidda, S and De Simone, B and Di Saverio, S and Finotti, E and Kenji, I and Moore, E and Wexner, S and Biffl, W and Coimbra, R and Guttadauro, A and Leppäniemi, A and Maier, R and Magnone, S and Mefire, AC and Peitzmann, A and Sakakushev, B and Sugrue, M and Viale, P and Weber, D and Kashuk, J and Fraga, GP and Kluger, I and Catena, F and Ansaloni, L}, title = {2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation.}, journal = {World journal of emergency surgery : WJES}, volume = {13}, number = {}, pages = {36}, pmid = {30123315}, issn = {1749-7922}, mesh = {Colectomy/methods ; Colorectal Neoplasms/*therapy ; Colostomy/methods ; Guidelines as Topic/*standards ; Humans ; Intestinal Obstruction/diagnosis/*therapy ; Intestinal Perforation/diagnosis/*therapy ; Self Expandable Metallic Stents ; Tomography, X-Ray Computed/methods ; }, abstract = {&#x115f;: Obstruction and perforation due to colorectal cancer represent challenging matters in terms of diagnosis, life-saving strategies, obstruction resolution and oncologic challenge. The aims of the current paper are to update the previous WSES guidelines for the management of large bowel perforation and obstructive left colon carcinoma (OLCC) and to develop new guidelines on obstructive right colon carcinoma (ORCC).<br><br>METHODS: The literature was extensively queried for focused publication until December 2017. Precise analysis and grading of the literature has been performed by a working group formed by a pool of experts: the statements and literature review were presented, discussed and voted at the Consensus Conference of the 4th Congress of the World Society of Emergency Surgery (WSES) held in Campinas in May 2017.<br><br>RESULTS: CT scan is the best imaging technique to evaluate large bowel obstruction and perforation. For OLCC, self-expandable metallic stent (SEMS), when available, offers interesting advantages as compared to emergency surgery; however, the positioning of SEMS for surgically treatable causes carries some long-term oncologic disadvantages, which are still under analysis. In the context of emergency surgery, resection and primary anastomosis (RPA) is preferable to Hartmann's procedure, whenever the characteristics of the patient and the surgeon are permissive. Right-sided loop colostomy is preferable in rectal cancer, when preoperative therapies are predicted.With regards to the treatment of ORCC, right colectomy represents the procedure of choice; alternatives, such as internal bypass and loop ileostomy, are of limited value.Clinical scenarios in the case of perforation might be dramatic, especially in case of free faecal peritonitis. The importance of an appropriate balance between life-saving surgical procedures and respect of oncologic caveats must be stressed. In selected cases, a damage control approach may be required.Medical treatments including appropriate fluid resuscitation, early antibiotic treatment and management of co-existing medical conditions according to international guidelines must be delivered to all patients at presentation.<br><br>CONCLUSIONS: The current guidelines offer an extensive overview of available evidence and a qualitative consensus regarding management of large bowel obstruction and perforation due to colorectal cancer.}, }
@article {pmid30118620, year = {2019}, author = {Farowski, F and Els, G and Tsakmaklis, A and Higgins, PG and Kahlert, CR and Stein-Thoeringer, CK and Bobardt, JS and Dettmer-Wilde, K and Oefner, PJ and Vehreschild, JJ and Vehreschild, MJGT}, title = {Assessment of urinary 3-indoxyl sulfate as a marker for gut microbiota diversity and abundance of Clostridiales.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {133-141}, pmid = {30118620}, issn = {1949-0984}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Anti-Bacterial Agents/pharmacology ; Biodiversity ; Biomarkers/*urine ; Clostridiales/*classification/drug effects/genetics/*isolation &amp; purification ; Clostridium Infections/*diagnosis ; Cohort Studies ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/drug effects/genetics ; Humans ; Indican/*urine ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVES: After allogeneic hematopoietic stem cell transplantation (allo-HCT), urinary levels of 3-indoxyl sulfate (3-IS) correlate with the relative abundance of bacteria from the class Clostridia (RAC), and antibiotic treatment is considered the major determinant of this outcome. A high RAC has been associated with favorable outcome after allo-HCT and protection from Clostridium difficile infection (CDI). We assessed correlations between alpha diversity, RAC and urinary 3-IS levels in a non-allo-HCT clinical cohort of antibiotic treated patients to further explore 3-IS as a biomarker of reduced diversity and predisposition to CDI.<br><br>METHODS: Fecal and urinary specimens were analyzed from 40 non-allo-HCT hospitalized patients before and 9&#xa0;&#xb1;&#xa0;2&#xa0;days after initiation of intravenous antibiotic treatment. Fecal microbiota were analyzed by 16s RNA sequencing and urinary 3-IS was analyzed by liquid chromatography-tandem mass spectrometry. Receiver operating characteristic (ROC) analysis was performed to assess the predictive value of 3-IS.<br><br>RESULTS: At a RAC cutoff of <30%, the binary logarithm of 3-IS (medium 3-IS: &#x2264;2.5; high 3-IS: >2.5) was predictive with an accuracy of 82% (negative predictive value: 87%, positive predictive value 67%). Accuracy was improved by combing antibiotic history with 3-IS levels (accuracy 89%, npv 88%, ppv 92%).<br><br>CONCLUSION: In conjunction with patient antibiotic history, 3-IS is a candidate marker to predict RAC.}, }
@article {pmid30109576, year = {2018}, author = {Biehl, LM and Cruz Aguilar, R and Farowski, F and Hahn, W and Nowag, A and Wisplinghoff, H and Vehreschild, MJGT}, title = {Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection.}, journal = {Infection}, volume = {46}, number = {6}, pages = {871-874}, pmid = {30109576}, issn = {1439-0973}, support = {BI 1899/1-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Fecal Microbiota Transplantation ; Female ; Germany ; Humans ; *Kidney Transplantation ; Middle Aged ; Recurrence ; *Transplant Recipients ; Treatment Outcome ; Urinary Tract Infections/*therapy ; }, abstract = {PURPOSE: We report on a kidney transplant recipient treated with fecal microbiota transplantation (FMT) for recurrent urinary tract infections.<br><br>METHODS: FMT was administered via frozen capsulized microbiota. Before and after FMT, urinary, fecal and vaginal microbiota compositions were analyzed.<br><br>RESULTS: The patient remained without symptoms after FMT.<br><br>CONCLUSIONS: Underlying mechanisms of action need to be addressed in depth by future research.}, }
@article {pmid30108329, year = {2019}, author = {Schmidlin, N and Passweg, JR and Halter, JP and Heim, D and Infanti, L and Stern, A and Plattner, A and Plattner, R and Medinger, M and Kleber, M and Rothen, C and Buser, A and Bucher, C and Holbro, A}, title = {Baseline calprotectin fails to predict incidence of acute gastrointestinal graft vs. host disease: a prospective study.}, journal = {Bone marrow transplantation}, volume = {54}, number = {2}, pages = {343-347}, doi = {10.1038/s41409-018-0292-4}, pmid = {30108329}, issn = {1476-5365}, mesh = {Adult ; Aged ; Biomarkers/analysis ; Feces/chemistry ; Female ; Gastrointestinal Diseases/diagnosis/etiology ; Graft vs Host Disease/*diagnosis/etiology/pathology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Incidence ; Leukocyte L1 Antigen Complex/*analysis ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Young Adult ; }, }
@article {pmid30107075, year = {2018}, author = {Nishio Lucar, A and Knicely, DH and Sifri, CD}, title = {Late post-kidney transplant Strongyloides hyperinfection syndrome.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {20}, number = {6}, pages = {e12975}, doi = {10.1111/tid.12975}, pmid = {30107075}, issn = {1399-3062}, mesh = {Aged ; Animals ; Antiparasitic Agents/therapeutic use ; Feces/parasitology ; Female ; Humans ; Immunocompromised Host ; Ivermectin/therapeutic use ; Kidney Transplantation/*adverse effects ; Strongyloides stercoralis/*isolation &amp; purification ; Strongyloidiasis/*diagnosis/drug therapy/immunology/parasitology ; Superinfection/*diagnosis/drug therapy/immunology/parasitology ; Time Factors ; }, abstract = {Disseminated strongyloidiasis is a potentially life-threatening infection in organ transplant recipients that typically occurs within the first 6 months of transplantation. We discuss a patient from the Appalachia region of Virginia who appeared to acquire Strongyloides stercoralis domestically years after kidney transplantation and then develop disseminated strongyloidiasis.}, }
@article {pmid30105528, year = {2018}, author = {Frye, RE}, title = {Social Skills Deficits in Autism Spectrum Disorder: Potential Biological Origins and Progress in Developing Therapeutic Agents.}, journal = {CNS drugs}, volume = {32}, number = {8}, pages = {713-734}, pmid = {30105528}, issn = {1179-1934}, mesh = {Autism Spectrum Disorder/*complications/psychology ; Bumetanide/therapeutic use ; Disease Progression ; Fecal Microbiota Transplantation/methods ; Humans ; Social Behavior Disorders/*etiology/*therapy ; *Social Skills ; Sodium Potassium Chloride Symporter Inhibitors/therapeutic use ; Vasopressins/metabolism ; }, abstract = {Autism spectrum disorder is defined by two core symptoms: a deficit in social communication and the presence of repetitive behaviors and/or restricted interests. Currently, there is no US Food and Drug Administration-approved drug for these core symptoms. This article reviews the biological origins of the social function deficit associated with autism spectrum disorder and the drug therapies with the potential to treat this deficit. A review of the history of autism demonstrates that a deficit in social interaction has been the defining feature of the concept of autism from its conception. Abnormalities identified in early social skill development and an overview of the pathophysiology abnormalities associated with autism spectrum disorder are discussed as are the abnormalities in brain circuits associated with the social function deficit. Previous and ongoing clinical trials examining agents that have the potential to improve social deficits associated with autism spectrum disorder are discussed in detail. This discussion reveals that agents such as oxytocin and propranolol are particularly promising and undergoing active investigation, while other agents such as vasopressin agonists and antagonists are being activity investigated but have limited published evidence at this time. In addition, agents such as bumetanide and manipulation of the enteric microbiome using microbiota transfer therapy appear to have promising effects on core autism spectrum disorder symptoms including social function. Other pertinent issues associated with developing treatments in autism spectrum disorder, such as disease heterogeneity, high placebo response rates, trial design, and the most appropriate way of assessing effects on social skills (outcome measures), are also discussed.}, }
@article {pmid30102568, year = {2019}, author = {Lieber, AD and Beier, UH and Xiao, H and Wilkins, BJ and Jiao, J and Li, XS and Schugar, RC and Strauch, CM and Wang, Z and Brown, JM and Hazen, SL and Bokulich, NA and Ruggles, KV and Akimova, T and Hancock, WW and Blaser, MJ}, title = {Loss of HDAC6 alters gut microbiota and worsens obesity.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {1}, pages = {1098-1109}, pmid = {30102568}, issn = {1530-6860}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; U01 AI122285/AI/NIAID NIH HHS/United States ; P50 CA150964/CA/NCI NIH HHS/United States ; P01 AI073489/AI/NIAID NIH HHS/United States ; K08 AI095353/AI/NIAID NIH HHS/United States ; R56 AI095276/AI/NIAID NIH HHS/United States ; R01 DK090989/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteroides/isolation &amp; purification ; Diet, High-Fat ; Fatty Liver/genetics ; Feces ; *Gastrointestinal Microbiome ; Germ-Free Life ; Histone Deacetylase 6/genetics/*physiology ; Hyperlipidemias/genetics ; Lactobacillus/isolation &amp; purification ; Male ; Mesentery/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/*genetics/immunology/*microbiology ; Spleen/pathology ; T-Lymphocytes, Regulatory/immunology ; Up-Regulation ; Weight Gain ; }, abstract = {Alterations in gut microbiota are known to affect intestinal inflammation and obesity. Antibiotic treatment can affect weight gain by elimination of histone deacetylase (HDAC) inhibitor-producing microbes, which are anti-inflammatory by augmenting regulatory T (Treg) cells. We asked whether mice that lack HDAC6 and have potent suppressive Treg cells are protected from microbiota-induced accelerated weight gain. We crossed wild-type and HDAC6-deficient mice and subjected the offspring to perinatal penicillin, inducing weight gain via microbiota disturbance. We observed that male HDAC6-deficient mice were not protected and developed profoundly accelerated weight gain. The antibiotic-exposed HDAC6-deficient mice showed a mixed immune phenotype with increased CD4[+] and CD8[+] T-cell activation yet maintained the enhanced Treg cell-suppressive function phenotype characteristic of HDAC6-deficient mice. 16S rRNA sequencing of mouse fecal samples reveals that their microbiota diverged with time, with HDAC6 deletion altering microbiome composition. On a high-fat diet, HDAC6-deficient mice were depleted in representatives of the S24-7 family and Lactobacillus but enriched with Bacteroides and Parabacteroides; these changes are associated with obesity. Our findings further our understanding of the influence of HDACs on microbiome composition and are important for the development of HDAC6 inhibitors in the treatment of human diseases.-Lieber, A. D., Beier, U. H., Xiao, H., Wilkins, B. J., Jiao, J., Li, X. S., Schugar, R. C., Strauch, C. M., Wang, Z., Brown, J. M., Hazen, S. L., Bokulich, N. A., Ruggles, K. V., Akimova, T., Hancock, W. W., Blaser, M. J. Loss of HDAC6 alters gut microbiota and worsens obesity.}, }
@article {pmid30100156, year = {2019}, author = {Pignanelli, M and Bogiatzi, C and Gloor, G and Allen-Vercoe, E and Reid, G and Urquhart, BL and Ruetz, KN and Velenosi, TJ and Spence, JD}, title = {Moderate Renal Impairment and Toxic Metabolites Produced by the Intestinal Microbiome: Dietary Implications.}, journal = {Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation}, volume = {29}, number = {1}, pages = {55-64}, doi = {10.1053/j.jrn.2018.05.007}, pmid = {30100156}, issn = {1532-8503}, support = {133416//CIHR/Canada ; }, mesh = {Aged ; Chromatography, Liquid ; Cohort Studies ; Cresols/blood ; Diet/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*metabolism/microbiology ; Glucuronides/blood ; Hippurates/blood ; Humans ; Kidney/physiopathology ; Male ; Mass Spectrometry ; Methylamines/blood ; Renal Insufficiency/*blood/*physiopathology ; Sulfuric Acid Esters/blood ; Toxins, Biological/*blood ; }, abstract = {OBJECTIVE: Toxic metabolites produced by the intestinal microbiome from animal proteins, carnitine (mainly from red meat), or phosphatidylcholine (mainly from egg yolk), have important adverse effects on cardiovascular disease. These are renally eliminated and may be termed gut-derived uremic toxins (GDUT). We hypothesized that even moderate renal impairment and intake of nutrient precursors would raise plasma levels of GDUT.<br><br>DESIGN: A cohort study.<br><br>SETTING: Academic medical center.<br><br>SUBJECTS: Patients attending stroke prevention clinics at a university medical center were recruited.<br><br>MAIN OUTCOME MEASURE: Nutrient intake was assessed by the 131-item Harvard Food Frequency Questionnaire; estimated glomerular filtration rate (eGFR) was caculated using the Chronic Kidney Disease-Epidemiology (EPI) equations. Plasma levels of trimethylamine n-oxide, p-cresyl sulfate, hippuric acid, p-cresyl glucuronide, pheny acetyl glutamine, and phenyl sulfate were measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.<br><br>RESULTS: Among 316 patients recruited, the mean (standard deviation [SD]) age was 66.74 (10.42) years; 59.7% were men. Mean eGFR was 76.03&#xa0;&#xb1;&#xa0;20.01; 57 (18%) had eGFR<60&#xa0;mL/min/1.73&#xa0;m[2]. Plasma levels of all GDUT were significantly higher even with moderate reduction of eGFR. Nutrient intake affected plasma levels of some GDUT; the effects differed by eGFR above and below 60&#xa0;mL/min/1.73&#xa0;m[2]. Plasma levels were obtained fasting, so we probably underestimated the effect of nutrient intake.<br><br>CONCLUSIONS: Even moderate impairment of renal function was associated with higher plasma levels of GDUT. This has dietary implications for patients at risk of atherosclerosis, particularly in those with impaired renal function (including the elderly): they should limit intake of animal protein, red meat, and egg yolk. It also points the way to novel approaches to vascular prevention, including more intensive dialysis, renal transplantation, and modification of the intestinal microbiome with probiotics or fecal transplantation.}, }
@article {pmid30099108, year = {2019}, author = {Colombel, JF and Shin, A and Gibson, PR}, title = {AGA Clinical Practice Update on Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: Expert Review.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {3}, pages = {380-390.e1}, pmid = {30099108}, issn = {1542-7714}, support = {KL2 TR001106/TR/NCATS NIH HHS/United States ; TL1 TR001107/TR/NCATS NIH HHS/United States ; UL1 TR001108/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Disease Management ; *Gastrointestinal Diseases/diagnosis/therapy ; *Inflammatory Bowel Diseases/diagnosis/therapy ; Practice Guidelines as Topic ; }, abstract = {DESCRIPTION: The purpose of this clinical practice update review is to describe key principles in the diagnosis and management of functional gastrointestinal (GI) symptoms in patients with inflammatory bowel disease (IBD).<br><br>METHODS: The evidence and best practices summarized in this manuscript are based on relevant scientific publications, systematic reviews, and expert opinion where applicable. Best practice advice 1: A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging). Best practice advice 2: In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management. Best practice advice 3: Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation. Best practice advice 4: Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns. Best practice advice 5: A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy. Best practice advice 6: Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms. Best practice advice 7: Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation. Best practice advice 8: Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD. Best practice advice 9: Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD while use of opiates should be avoided. Best practice advice 10: Probiotics may be considered for treatment of functional symptoms in IBD. Best practice advice 11: Pelvic floor therapy should be offered to IBD patients with evidence of an underlying defecatory disorder. Best practice advice 12: Until further evidence is available, fecal microbiota transplant should not be offered for treatment of functional GI symptoms in IBD. Best practice advice 13: Physical exercise should be encourage in IBD patients with functional GI symptoms. Best practice advice 14: Until further evidence is available, complementary and alternative therapies should not be routinely offered for functional symptoms in IBD. This Clinical Practice Update was produced by the AGA Institute.}, }
@article {pmid30099098, year = {2019}, author = {Acharya, C and Bajaj, JS}, title = {Altered Microbiome in Patients With Cirrhosis and Complications.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {2}, pages = {307-321}, pmid = {30099098}, issn = {1542-7714}, support = {I01 CX001076/CX/CSRD VA/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; }, mesh = {*Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis/*complications/microbiology ; Liver Failure/*complications/microbiology ; *Microbiota ; }, abstract = {In patients with cirrhosis, the gut microbiome are affected by multiple gut and systemic alterations. These changes lead to dysbiosis in the microbiota of different parts of the body, resulting in inflammation. The constant immune stimulation resulting in part from dysbiosis is associated with morbidity in patients with cirrhosis. Dysbiosis as a dynamic event worsens with decompensation such as with hepatic encephalopathy, infections or acute-on-chronic liver failure (ACLF). These microbial patterns could be applied as diagnostic and prognostic measures in cirrhosis in the outpatient and inpatient setting. Current therapies for cirrhosis have differing impacts on gut microbial composition and functionality. Dietary modifications and the oral cavity have emerged as newer targetable factors to modulate the microbiome, which could affect inflammation and, potentially improve outcomes. Additionally, fecal microbial transplant is being increasingly studied to provide compositional and functional modulation of the microbiome. Ultimately, a combination of targeted therapies may be needed to provide an optimal gut milieu to improve outcomes in cirrhosis.}, }
@article {pmid30093802, year = {2018}, author = {Filip, M and Tzaneva, V and Dumitrascu, DL}, title = {Fecal transplantation: digestive and extradigestive clinical applications.}, journal = {Clujul medical (1957)}, volume = {91}, number = {3}, pages = {259-265}, pmid = {30093802}, issn = {1222-2119}, abstract = {BACKGROUND AND AIM: Fecal transplantation or fecal material transplantation (FMT) became a hot topic in gastroenterology in recent years. Therefore it is important to disseminate the up-to-date information on FMT. The aim of the paper is to review the knowledge on FMT and its clinical applications.<br><br>METHODS: An extensive review of the literature was carried out. Titles from Pubmed were searched and analyzed. A narrative review has been written with emphasis on indications of FMT in different conditions.<br><br>RESULTS: The guidelines recommend FMT in relapsing infection with Clostridium difficile. Several attempts to use FMT in other conditions have been analyzed. Attempts were recorded in other bowel disorders like IBD, IBS, chronic constipation and even colorectal cancer. The attempt to change the microbiota by FMT in diabetes and obesity represent challenges for the future.<br><br>CONCLUSIONS: Fecal transplantation represents an important therapeutic method, intensively investigated these years. Beside the indication for persistent and recurrent Clostridium difficile infection, several attempts were undertaken in other intestinal diseases and in metabolic conditions. The efficiency of these applications has to be demonstrated.}, }
@article {pmid30090049, year = {2018}, author = {Micic, D and Hirsch, A and Setia, N and Rubin, DT}, title = {Enteric infections complicating ulcerative colitis.}, journal = {Intestinal research}, volume = {16}, number = {3}, pages = {489-493}, pmid = {30090049}, issn = {1598-9100}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; }, abstract = {Enteric infections have previously been postulated to play a role in the pathogenesis of inflammatory bowel disease (IBD), however, little evidence exists in the etiologic role of specific enteric infections in the development of IBD. When encountered in the setting of IBD, enteric infections pose a clinical challenge in management given the competing treatment strategies for infectious conditions and autoimmune disorders. Here we present the case of a young male with enteric infections complicating a new diagnosis of IBD. Our patient's initial clinical presentation included diagnoses of Klebsiella oxytoca isolation and Clostridium difficile infection. Directed therapies to include withdrawal of antibiotics and fecal microbiota transplantation were performed without resolution of clinical symptoms. Given persistence of symptoms and active colitis, the patient was diagnosed with ulcerative colitis (UC), requiring treatments directed at severe UC to include cyclosporine therapy. The finding of multiple enteric infections in a newly presenting patient with IBD is an unexpected finding that has treatment implications.}, }
@article {pmid30090033, year = {2018}, author = {Yu, LC and Wei, SC and Ni, YH}, title = {Impact of microbiota in colorectal carcinogenesis: lessons from experimental models.}, journal = {Intestinal research}, volume = {16}, number = {3}, pages = {346-357}, pmid = {30090033}, issn = {1598-9100}, abstract = {A role of gut microbiota in colorectal cancer (CRC) growth was first suggested in germ-free rats almost 50 years ago, and the existence of disease-associated bacteria (termed pathobionts) had becoming increasingly evident from experimental data of fecal transplantation, and microbial gavage or monoassociation. Altered bacterial compositions in fecal and mucosal specimens were observed in CRC patients compared to healthy subjects. Microbial fluctuations were found at various cancer stages; an increase of bacterial diversity was noted in the adenoma specimens, while a reduction of bacterial richness was documented in CRC samples. The bacterial species enriched in the human cancerous tissues included Escherichia coli, Fusobacterium nucleatum, and enterotoxigenic Bacteroides fragilis. The causal relationship of gut bacteria in tumorigenesis was established by introducing particular bacterial strains in in situ mouse CRC models. Detailed experimental protocols of bacterial gavage and the advantages and caveats of different experimental models are summarized in this review. The microbial genotoxins, enterotoxins, and virulence factors implicated in the mechanisms of bacteria-driven tumorigenesis are described. In conclusion, intestinal microbiota is involved in colon tumorigenesis. Bacteria-targeting intervention would be the next challenge for CRC.}, }
@article {pmid30089902, year = {2018}, author = {Fulde, M and Sommer, F and Chassaing, B and van Vorst, K and Dupont, A and Hensel, M and Basic, M and Klopfleisch, R and Rosenstiel, P and Bleich, A and Bäckhed, F and Gewirtz, AT and Hornef, MW}, title = {Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {489-493}, doi = {10.1038/s41586-018-0395-5}, pmid = {30089902}, issn = {1476-4687}, mesh = {Aging/genetics/*immunology ; Animals ; Animals, Newborn/genetics/*immunology ; Crosses, Genetic ; Environment ; Female ; Flagellin/immunology/metabolism ; Gastrointestinal Microbiome/genetics/*immunology ; Homeostasis ; Host Microbial Interactions ; Housing, Animal ; Intestinal Mucosa/cytology/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Pregnancy ; Toll-Like Receptor 5/genetics/*immunology ; }, abstract = {Alterations in enteric microbiota are associated with several highly prevalent immune-mediated and metabolic diseases[1-3], and experiments involving faecal transplants have indicated that such alterations have a causal role in at least some such conditions[4-6]. The postnatal period is particularly critical for the development of microbiota composition, host-microbe interactions and immune homeostasis[7-9]. However, the underlying molecular mechanisms of this neonatal priming period have not been defined. Here we report the identification of a host-mediated regulatory circuit of bacterial colonization that acts solely during the early neonatal period but influences life-long microbiota composition. We demonstrate age-dependent expression of the flagellin receptor Toll-like receptor 5 (TLR5) in the gut epithelium of neonate mice. Using competitive colonization experiments, we demonstrate that epithelial TLR5-mediated REG3γ production is critical for the counter-selection of colonizing flagellated bacteria. Comparative microbiota transfer experiments in neonate and adult wild-type and Tlr5-deficient germ-free mice reveal that neonatal TLR5 expression strongly influences the composition of the microbiota throughout life. Thus, the beneficial microbiota in the adult host is shaped during early infancy. This might explain why environmental factors that disturb the establishment of the microbiota during early life can affect immune homeostasis and health in adulthood.}, }
@article {pmid30087270, year = {2018}, author = {Gagliardi, A and Totino, V and Cacciotti, F and Iebba, V and Neroni, B and Bonfiglio, G and Trancassini, M and Passariello, C and Pantanella, F and Schippa, S}, title = {Rebuilding the Gut Microbiota Ecosystem.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {8}, pages = {}, pmid = {30087270}, issn = {1660-4601}, mesh = {Dysbiosis/microbiology/*prevention &amp; control ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Microbial Consortia ; Phage Therapy ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage/therapeutic use ; Synbiotics/administration &amp; dosage ; }, abstract = {A microbial ecosystem in which bacteria no longer live in a mutualistic association is called dysbiotic. Gut microbiota dysbiosis is a condition related with the pathogenesis of intestinal illnesses (irritable bowel syndrome, celiac disease, and inflammatory bowel disease) and extra-intestinal illnesses (obesity, metabolic disorder, cardiovascular syndrome, allergy, and asthma). Dysbiosis status has been related to various important pathologies, and many therapeutic strategies aimed at restoring the balance of the intestinal ecosystem have been implemented. These strategies include the administration of probiotics, prebiotics, and synbiotics; phage therapy; fecal transplantation; bacterial consortium transplantation; and a still poorly investigated approach based on predatory bacteria. This review discusses the various aspects of these strategies to counteract intestinal dysbiosis.}, }
@article {pmid30085388, year = {2019}, author = {Cheng, YW and Phelps, E and Ganapini, V and Khan, N and Ouyang, F and Xu, H and Khanna, S and Tariq, R and Friedman-Moraco, RJ and Woodworth, MH and Dhere, T and Kraft, CS and Kao, D and Smith, J and Le, L and El-Nachef, N and Kaur, N and Kowsika, S and Ehrlich, A and Smith, M and Safdar, N and Misch, EA and Allegretti, JR and Flynn, A and Kassam, Z and Sharfuddin, A and Vuppalanchi, R and Fischer, M}, title = {Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {19}, number = {2}, pages = {501-511}, pmid = {30085388}, issn = {1600-6143}, support = {UM1 AI104681/AI/NIAID NIH HHS/United States ; TL1 TR002382/TR/NCATS NIH HHS/United States ; //IU GI Divisional Research Grant/International ; UL1 TR000454/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; }, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/epidemiology/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Organ Transplantation/*adverse effects ; Recurrence ; Retrospective Studies ; Transplant Recipients/*statistics &amp; numerical data ; Treatment Outcome ; United States/epidemiology ; }, abstract = {Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.}, }
@article {pmid30084095, year = {2019}, author = {Dicks, LMT and Mikkelsen, LS and Brandsborg, E and Marcotte, H}, title = {Clostridium difficile, the Difficult "Kloster" Fuelled by Antibiotics.}, journal = {Current microbiology}, volume = {76}, number = {6}, pages = {774-782}, pmid = {30084095}, issn = {1432-0991}, mesh = {Anti-Bacterial Agents/*adverse effects/therapeutic use ; Clostridioides difficile/*drug effects/*growth &amp; development ; Clostridium Infections/*microbiology/pathology ; Colitis/complications/*microbiology/pathology/therapy ; *Drug Resistance, Bacterial ; Dysbiosis/*chemically induced ; Fecal Microbiota Transplantation/methods ; Humans ; Multiple Organ Failure ; Probiotics/administration &amp; dosage ; }, abstract = {Clostridium difficile is normally present in low numbers in a healthy adult gastro-intestinal tract (GIT). Drastic changes in the microbial population, e.g., dysbiosis caused by extensive treatment with antibiotics, stimulates the growth of resistant strains and the onset of C. difficile infection (CDI). Symptoms of infection varies from mild diarrhea to colitis (associated with dehydration and bleeding), pseudomembranous colitis with yellow ulcerations in the mucosa of the colon, to fulminant colitis (perforation of the gut membrane), and multiple organ failure. Inflamed epithelial cells and damaged mucosal tissue predisposes the colon to other opportunistic pathogens such as Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida spp., and Salmonella spp. This may lead to small intestinal bacterial overgrowth (SIBO), sepsis, toxic megacolon, and even colorectal cancer. Many stains of C. difficile are resistant to metronidazole and vancomycin. Vaccination may be an answer to CDI, but requires more research. Success in treatment with probiotics depends on the strains used. Oral or rectal fecal transplants are partly effective, as spores in the small intestine may germinate and colonize the colon. The effect of antibiotics on C. difficile and commensal gut microbiota is summarized and changes in gut physiology are discussed. The need to search for non-antibiotic methods in the treatment of CDI and C. difficile-associated disease (CDAD) is emphasized.}, }
@article {pmid30083142, year = {2018}, author = {Niederwerder, MC and Constance, LA and Rowland, RRR and Abbas, W and Fernando, SC and Potter, ML and Sheahan, MA and Burkey, TE and Hesse, RA and Cino-Ozuna, AG}, title = {Fecal Microbiota Transplantation Is Associated With Reduced Morbidity and Mortality in Porcine Circovirus Associated Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1631}, pmid = {30083142}, issn = {1664-302X}, abstract = {Porcine circovirus associated disease (PCVAD) is a term used to describe the multi-factorial disease syndromes caused by porcine circovirus type 2 (PCV-2), which can be reproduced in an experimental setting through the co-infection of pigs with PCV-2 and porcine reproductive and respiratory syndrome virus (PRRSV). The resulting PCVAD-affected pigs represent a subpopulation within the co-infected group. In co-infection studies, the presence of increased microbiome diversity is linked to a reduction in clinical signs. In this study, fecal microbiota transplantation (FMT) was investigated as a means to prevent PCVAD in pigs co-infected with PRRSV and PCV-2d. The sources of the FMT material were high-parity sows with a documented history of high health status and robust litter characteristics. The analysis of the donated FMT material showed the absence of common pathogens along with the presence of diverse microbial phyla and families. One group of pigs (n = 10) was administered the FMT while a control group (n = 10) was administered a sterile mock-transplant. Over the 42-day post-infection period, the FMT group showed fewer PCVAD-affected pigs, as evidenced by a significant reduction in morbidity and mortality in transplanted pigs, along with increased antibody levels. Overall, this study provides evidence that FMT decreases the severity of clinical signs following co-infection with PRRSV and PCV-2 by reducing the prevalence of PCVAD.}, }
@article {pmid30081949, year = {2018}, author = {Montassier, E and Al-Ghalith, GA and Hillmann, B and Viskocil, K and Kabage, AJ and McKinlay, CE and Sadowsky, MJ and Khoruts, A and Knights, D}, title = {CLOUD: a non-parametric detection test for microbiome outliers.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {137}, pmid = {30081949}, issn = {2049-2618}, mesh = {Bacteria/*classification ; Clostridioides difficile/pathogenicity ; Clostridium Infections/microbiology/*therapy ; Computational Biology/*methods ; Dysbiosis/*diagnosis ; Enterocolitis/microbiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; }, abstract = {BACKGROUND: Dysbiosis of the human gut microbiome is defined as a maladaptive or clinically relevant deviation of the community profile from the healthy or normal state. Dysbiosis has been implicated in an extensive set of metabolic, auto-immune, and infectious diseases, and yet there is substantial inter-individual variation in microbiome composition even within body sites of healthy humans. An individual's microbiome varies over time in a high-dimensional space to form their personal microbiome cloud. This cloud may or may not be similar to that of other people, both in terms of the average microbiome profile (conformity) and the diameter of the cloud (stability). However, there is currently no robust non-parametric test that determines whether a patient's microbiome cloud is an outlier with respect to a reference group of healthy individuals with widely varying microbiome profiles.<br><br>METHODS: Here, we propose a test for outliers' detection in the human gut microbiome that accounts for the wide range of microbiome phenotypes observed in a typical set of healthy individuals and for intra-individual temporal variation. Our robust nonparametric outlier detection test, the CLOUD test, performs two assessments of a patient's microbiome health: conformity, the extent to which the patient's microbiome cloud is ecologically similar to a subset of healthy subjects; and stability, which compares the cloud diameter of a patient to those of healthy subjects. The CLOUD test is based on locally linear embedded ecological distances, allowing it to account for widely varying microbiome compositions among reference individuals. It also leverages temporal variability within patients and reference individuals to increase the robustness of the test.<br><br>RESULTS: We describe the CLOUD test, and we apply it to one novel and two previously published cohorts of patients receiving fecal microbiota transplantation for recurrent Clostridium difficile colitis, as well as to two known healthy cohorts, demonstrating high concordance of the CLOUD conformity and stability indices with clinical outcomes.<br><br>CONCLUSIONS: Although the CLOUD test is not, on its own, a test for clinical dysbiosis, it nonetheless provides a framework for outlier testing that could be incorporated into evaluation of suspected dysbiosis, which may play a role in diagnosis and prognosis of numerous pediatric and adult diseases.}, }
@article {pmid30081576, year = {2018}, author = {Roncoroni, L and Bascuñán, KA and Doneda, L and Scricciolo, A and Lombardo, V and Branchi, F and Ferretti, F and Dell'Osso, B and Montanari, V and Bardella, MT and Elli, L}, title = {A Low FODMAP Gluten-Free Diet Improves Functional Gastrointestinal Disorders and Overall Mental Health of Celiac Disease Patients: A Randomized Controlled Trial.}, journal = {Nutrients}, volume = {10}, number = {8}, pages = {}, pmid = {30081576}, issn = {2072-6643}, mesh = {Adult ; Celiac Disease/diagnosis/*diet therapy/physiopathology/psychology ; *Diet, Carbohydrate-Restricted ; *Diet, Gluten-Free ; Digestion ; Double-Blind Method ; Female ; Fermentation ; Health Status ; Humans ; Italy ; Male ; *Mental Health ; Middle Aged ; Quality of Life ; Remission Induction ; Time Factors ; Treatment Outcome ; }, abstract = {A subset of patients with celiac disease (CD) on a gluten-free diet (GFD) reported the persistence of functional gastrointestinal disorders. Foods containing fermentable, oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can trigger a broad range of gastrointestinal symptoms in sensitive individuals. We evaluated the effects of a low FODMAP diet (LFD) on gastrointestinal and psychological symptomatology in CD patients. A total of 50 celiac patients on GFDs and with persistence of gastrointestinal symptoms were included. The patients were randomly allocated to one of two dietary groups-one on a low FODMAP GFD (LF-GFD, n = 25) and the other on a regular GFD (R-GFD, n = 25)-for 21 days. Psychological symptomatology and quality of life were evaluated by the Symptom Checklist-90-R (SCL-90) and the Short Form (36) Health Survey (SF-36) questionnaires, respectively. Gastrointestinal symptomatology and general well-being were evaluated by visual analogue scale (VAS) scores. After 21 days, 21 and 23 patients completed the dietary treatment on LF-GFD and R-GFD, respectively. A reduced global SCL-90 index (p < 0.0003) was found in the LF-GFD group but not in the R-GFD one. However, the SF-36 scores did not differ between groups after treatment. The VAS for abdominal pain was much lower, and the VAS for fecal consistency enhanced after treatment in the LF-GFD group. General well-being increased in both groups but with a much higher improvement in the LF-GFD (p = 0.03). A short-term LFD regimen helps to improve the psychological health and gastrointestinal symptomatology with enhanced well-being of CD patients with persisting functional gastrointestinal symptomatology. The long-term clinical effects of LFD in particular subgroups of CD patients need further evaluation.}, }
@article {pmid30081160, year = {2018}, author = {Zhang, JS and Li, L and Cheng, W and Hou, WY}, title = {Rex Shunt as a Treatment of Type II Abernethy Malformation with Severe Dysplasia of Portal Vein.}, journal = {Annals of vascular surgery}, volume = {53}, number = {}, pages = {268.e1-268.e6}, doi = {10.1016/j.avsg.2018.05.055}, pmid = {30081160}, issn = {1615-5947}, mesh = {Child ; Child, Preschool ; Computed Tomography Angiography ; Humans ; Iliac Vein/diagnostic imaging/physiopathology/*transplantation ; Ligation ; Male ; Mesenteric Veins/diagnostic imaging/physiopathology/*surgery ; Phlebography/methods ; Portal Vein/*abnormalities/diagnostic imaging/physiopathology/surgery ; Severity of Illness Index ; Treatment Outcome ; Vascular Malformations/diagnostic imaging/physiopathology/*surgery ; *Vascular Surgical Procedures ; Venous Pressure ; }, abstract = {BACKGROUND: Ligation of abnormal portosystemic shunt has been used to treat type II Abernethy malformation, but it may not be suitable for all patients. In this study, Rex shunt was carried out to manage type II Abernethy malformation with portal venous dysplasia. The outcomes are evaluated retrospectively.<br><br>METHODS: Between June 2014 and January 2015, 2 boys (age: 4.8 and 12.8&#xa0;years, respectively) with type II Abernethy malformation underwent Rex shunt with ligation of inferior mesenteric vein (IMV). The portal venous pressures were measured intraoperatively to decide the extent of inferior mesenteric venous ligation. An ileal vein (6&#xa0;mm in diameter) and a venae sigmoideae (7&#xa0;mm in diameter) were interposed between the left portal vein and superior mesenteric vein, respectively. To minimize postoperative portal hypertension, the IMV was partially ligated. Five months later, the IMV was completely ligated in a second operation because of persistent bloody stool and anemia (hemoglobin < 100&#xa0;g/L).<br><br>RESULTS: The duration of the operations was 180 and 240&#xa0;min. The extrahepatic portal pressure increased after bypass, but the portal pressure was less than 24 cm H2O in both patients. The fecal blood loss and frequency of hemafecia decreased after surgery. The bypass vein was patent, and the portal blood flow was shown increased on postoperative ultrasound and computed tomography. There was no hypersplenism and esophageal gastric varices.<br><br>CONCLUSIONS: The surgical management of Abernethy type II malformation should be individualized. Rex shunt with ligation of portosystemic shunt is feasible and effective in patients with severe dysplasia of portal vein.}, }
@article {pmid30078058, year = {2018}, author = {Singh, S}, title = {Evolution of Clinical Trials in Inflammatory Bowel Diseases.}, journal = {Current gastroenterology reports}, volume = {20}, number = {9}, pages = {41}, pmid = {30078058}, issn = {1534-312X}, mesh = {Clinical Trials as Topic/*standards ; Endoscopy, Gastrointestinal/standards ; Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*diagnosis/*therapy ; Patient Reported Outcome Measures ; }, abstract = {PURPOSE OF REVIEW: Since the first clinical trial of cortisone in ulcerative colitis in 1955, remarkable progress has been made in the design and conduct of clinical trials in inflammatory bowel diseases (IBD). In this review article, we will discuss evolution of clinical trials in IBD over the last 3-5 years.<br><br>RECENT FINDINGS: Recognizing limitations intrinsic to clinical disease activity indices in IBD, regulatory authorities have recommended evaluating co-primary endpoints of patient-reported outcomes and endoscopic disease activity in clinical trials. Biomarker-enriched trial enrolment and central endoscopy reading have emerged as critical events in trial recruitment and outcome assessment and have driven placebo response rates down. While trials of novel biologic therapies and advanced small molecules continue at an accelerated pace, pragmatic comparative efficacy trials of treatment strategy aimed at optimizing current therapies (such as early combined immunosuppression [REACT], tight disease control [CALM], therapeutic drug monitoring [TAXIT, TAILORIX]) have directly informed clinical practice. With emphasis on value-based care and population health management, multi-pronged remote monitoring, self-management, and telemedicine approaches in the era of smartphones have re-emerged with promise. Non-conventional therapies such as fecal microbiota transplantation, though still experimental, have provided insight into disease pathogenesis and offered hope for microbial manipulation strategies for treating these complex diseases. Clinical trials have rapidly evolved over the last 5&#xa0;years not only focusing on novel therapies but also optimizing existing treatment approaches and population health management. Over the next decade, these trials will continue to advance the field, and be readily translatable into clinical practice.}, }
@article {pmid30077182, year = {2018}, author = {Ye, Z and Zhang, N and Wu, C and Zhang, X and Wang, Q and Huang, X and Du, L and Cao, Q and Tang, J and Zhou, C and Hou, S and He, Y and Xu, Q and Xiong, X and Kijlstra, A and Qin, N and Yang, P}, title = {A metagenomic study of the gut microbiome in Behcet's disease.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {135}, pmid = {30077182}, issn = {2049-2618}, mesh = {Animals ; Bacteria/*classification/genetics/isolation &amp; purification ; Bacterial Capsules/genetics ; Behcet Syndrome/*microbiology ; Case-Control Studies ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Gene Expression Regulation, Bacterial ; Humans ; Male ; Metagenomics/*methods ; Mice ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Saliva/microbiology ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Behcet's disease (BD) is a recalcitrant, multisystemic inflammatory disease that can lead to irreversible blindness. Microbial agents have been considered to contribute to the pathogenesis of this disease, but the underlying mechanisms remain unclear. In this study, we investigated the association of gut microbiome composition with BD as well as its possible roles in the development of this disease.<br><br>METHODS: Fecal and saliva samples were collected from 32 active BD patients and 74 healthy controls. DNA extracted from fecal samples was subjected to metagenomic analysis, whereas DNA extracted from saliva samples was subjected to 16S rRNA gene sequencing analysis. The results were used to compare the composition and biological function of the microbiome between patients and healthy controls. Lastly, transplantation of pooled fecal samples from active BD patients into B10RIII mice undergoing experimental autoimmune uveitis (EAU) was performed to determine the causal relationship between the gut microbiome and BD.<br><br>RESULTS: Fecal samples from active BD patients were shown to be enriched in Bilophila spp., a sulfate-reducing bacteria (SRB) and several opportunistic pathogens (e.g., Parabacteroides spp. and Paraprevotella spp.) along with a lower level of butyrate-producing bacteria (BPB) Clostridium spp. and methanogens (Methanoculleus spp. Methanomethylophilus spp.). Analysis of microbial functions revealed that capsular polysaccharide transport system, oxidation-reduction process, type III, and type IV secretion systems were also increased in active BD patients. Network analysis showed that the BD-enriched SRB and opportunistic pathogens were positively correlated with each other, but they were negatively associated with the BPB and methanogens. Animal experiments revealed that fecal microbiota transplantation with feces from BD patients significantly exacerbated EAU activity and increased the production of inflammatory cytokines including IL-17 and IFN-&#x3b3;.<br><br>CONCLUSIONS: Our findings revealed that BD is associated with considerable gut microbiome changes, which is corroborated by a mouse study of fecal microbiota transplants. A model explaining the association of the gut microbiome composition with BD pathogenesis is proposed.}, }
@article {pmid30075573, year = {2018}, author = {Chehri, M and Christensen, AH and Halkjær, SI and Günther, S and Petersen, AM and Helms, M}, title = {Case series of successful treatment with fecal microbiota transplant (FMT) oral capsules mixed from multiple donors even in patients previously treated with FMT enemas for recurrent Clostridium difficile infection.}, journal = {Medicine}, volume = {97}, number = {31}, pages = {e11706}, pmid = {30075573}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Capsules ; Clostridium Infections/*therapy ; Denmark ; Drug Administration Routes ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; }, abstract = {RATIONALE: Studies have shown that fecal microbiota transplantation (FMT) is a safe and highly efficient treatment for recurrent Clostridium difficile infection (rCDI). However, it is still unknown if one versus multiple donors or enemas versus capsule FMT are most efficient.<br><br>PATIENT CONCERNS: 10 patients with at least 3 previous episodes of CDI were offered treatment with FMT capsules. 9 patients decided to participate.<br><br>DIAGNOSES: In this study, we treated 9 patients (25-86 years) with rCDI.<br><br>INTERVENTIONS: From October to November 2016, a total of 9 patients with recurrent CDI were treated with oral fecal microbiota capsules, with mixed donor feces from 4 donors with high microbiota diversity. All patients received treatment with vancomycin prior to the capsule regime.<br><br>OUTCOME: Patients had previous recurrences ranging from 2 to 10 recurrences. All 9 patients were successfully treated without recurrence after 180 days follow-up, even 2 patients previously treated with FMT enemas.<br><br>LESSONS: FMT capsules based on multiple donors are highly efficient in patients with rCDI.}, }
@article {pmid30074108, year = {2019}, author = {Bicknell, B and Liebert, A and Johnstone, D and Kiat, H}, title = {Photobiomodulation of the microbiome: implications for metabolic and inflammatory diseases.}, journal = {Lasers in medical science}, volume = {34}, number = {2}, pages = {317-327}, pmid = {30074108}, issn = {1435-604X}, mesh = {Animals ; Feces/microbiology ; Humans ; Inflammation/*radiotherapy ; *Low-Level Light Therapy ; Male ; Metabolic Diseases/*radiotherapy ; Mice, Inbred BALB C ; Microbiota/genetics/*radiation effects ; Phylogeny ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human microbiome is intimately associated with human health, with a role in obesity, metabolic diseases such as type 2 diabetes, and divergent diseases such as cardiovascular and neurodegenerative diseases. The microbiome can be changed by diet, probiotics, and faecal transplants, which has flow-on effects to health outcomes. Photobiomodulation has a therapeutic effect on inflammation and neurological disorders (amongst others) and has been reported to influence metabolic disorders and obesity. The aim of this study was to examine the possibility that PBM could influence the microbiome of mice. Mice had their abdomen irradiated with red (660 nm) or infrared (808 nm) low-level laser, either as single or multiple doses, over a 2-week period. Genomic DNA extracted from faecal pellets was pyrosequenced for the 16S rRNA gene. There was a significant (p < 0.05) difference in microbial diversity between PBM- and sham-treated mice. One genus of bacterium (Allobaculum) significantly increased (p < 0.001) after infrared (but not red light) PBM by day 14. Despite being a preliminary trial with small experimental numbers, we have demonstrated for the first time that PBM can alter microbiome diversity in healthy mice and increase numbers of Allobaculum, a bacterium associated with a healthy microbiome. This change is most probably a result of PBMt affecting the host, which in turn influenced the microbiome. If this is confirmed in humans, the possibility exists for PBMt to be used as an adjunct therapy in treatment of obesity and other lifestyle-related disorders, as well as cardiovascular and neurodegenerative diseases. The clinical implications of altering the microbiome using PBM warrants further investigation.}, }
@article {pmid30065967, year = {2018}, author = {Vargason, AM and Anselmo, AC}, title = {Clinical translation of microbe-based therapies: Current clinical landscape and preclinical outlook.}, journal = {Bioengineering &amp; translational medicine}, volume = {3}, number = {2}, pages = {124-137}, pmid = {30065967}, issn = {2380-6761}, abstract = {Next generation microbe-based therapeutics, inspired by the success of fecal microbiota transplants, are being actively investigated in clinical trials to displace or eliminate pathogenic microbes to treat various diseases in the gastrointestinal tract, skin, and vagina. Genetically engineered microbes are also being investigated in the clinic as drug producing factories for biologic delivery, which can provide a constant local source of drugs. In either case, microbe-therapeutics have the opportunity to address unmet clinical needs and open new areas of research by reducing clinical side effects associated with current treatment modalities or by facilitating the delivery of biologics. This review will discuss examples of past and current clinical trials that are investigating microbe-therapeutics, both microbiome-modulating and drug-producing, for the treatment of a range of diseases. We then offer a perspective on how preclinical approaches, both those focused on developing advanced delivery systems and those that use in vitro microbiome model systems to inform formulation design, will lead to the realization of next-generation microbe-therapeutics.}, }
@article {pmid30064988, year = {2019}, author = {Anhê, FF and Nachbar, RT and Varin, TV and Trottier, J and Dudonné, S and Le Barz, M and Feutry, P and Pilon, G and Barbier, O and Desjardins, Y and Roy, D and Marette, A}, title = {Treatment with camu camu (Myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice.}, journal = {Gut}, volume = {68}, number = {3}, pages = {453-464}, doi = {10.1136/gutjnl-2017-315565}, pmid = {30064988}, issn = {1468-3288}, support = {FDN#143247//CIHR/Canada ; }, mesh = {Animals ; Ascorbic Acid/therapeutic use ; Blood Glucose/metabolism ; Endotoxemia/prevention &amp; control ; Energy Metabolism/*physiology ; Fatty Liver/microbiology/physiopathology/prevention &amp; control ; Fecal Microbiota Transplantation ; Fruit/*chemistry ; Gastrointestinal Microbiome/*drug effects ; Homeostasis/physiology ; Male ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/microbiology/physiopathology/*prevention &amp; control ; Panniculitis/prevention &amp; control ; Plant Extracts/chemistry/pharmacology/therapeutic use ; }, abstract = {OBJECTIVE: The consumption of fruits is strongly associated with better health and higher bacterial diversity in the gut microbiota (GM). Camu camu (Myrciaria dubia) is an Amazonian fruit with a unique phytochemical profile, strong antioxidant potential and purported anti-inflammatory potential.<br><br>DESIGN: By using metabolic tests coupled with 16S rRNA gene-based taxonomic profiling and faecal microbial transplantation (FMT), we have assessed the effect of a crude extract of camu camu (CC) on obesity and associated immunometabolic disorders in high fat/high sucrose (HFHS)-fed mice.<br><br>RESULTS: Treatment of HFHS-fed mice with CC prevented weight gain, lowered fat accumulation and blunted metabolic inflammation and endotoxaemia. CC-treated mice displayed improved glucose tolerance and insulin sensitivity and were also fully protected against hepatic steatosis. These effects were linked to increased energy expenditure and upregulation of uncoupling protein 1 mRNA expression in the brown adipose tissue (BAT) of CC-treated mice, which strongly correlated with the mRNA expression of the membrane bile acid (BA) receptor TGR5. Moreover, CC-treated mice showed altered plasma BA pool size and composition and drastic changes in the GM (eg, bloom of Akkermansia muciniphila and a strong reduction of Lactobacillus). Germ-free (GF) mice reconstituted with the GM of CC-treated mice gained less weight and displayed higher energy expenditure than GF-mice colonised with the FM of HFHS controls.<br><br>CONCLUSION: Our results show that CC prevents visceral and liver fat deposition through BAT activation and increased energy expenditure, a mechanism that is dependent on the GM and linked to major changes in the BA pool size and composition.}, }
@article {pmid30060939, year = {2018}, author = {Pineton de Chambrun, G and Tassy, B and Kollen, L and Dufour, G and Valats, JC and Bismuth, M and Funakoshi, N and Panaro, F and Blanc, P}, title = {The treatment of refractory ulcerative colitis.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {32-33}, number = {}, pages = {49-57}, doi = {10.1016/j.bpg.2018.05.009}, pmid = {30060939}, issn = {1532-1916}, mesh = {Colitis, Ulcerative/pathology/*therapy ; Humans ; Quality of Life/*psychology ; Treatment Outcome ; }, abstract = {Ulcerative proctitis is defined as a mucosal inflammation limited to the rectum. Ulcerative proctitis is responsible for distressing symptoms and alteration of patient quality of life. Effective treatment is important to prevent or delay proximal extension of the disease and to improve quality of life. Refractory ulcerative proctitis is defined as the failure of topical and oral 5-aminosalicylic acid and corticosteroids. Medical management of refractory ulcerative proctitis may be challenging as there is little evidence regarding drug efficacy in this clinical situation. Data are currently available for azathioprine, topical tacrolimus and anti-TNF monoclonal antibodies as rescue treatment for refractory ulcerative proctitis. Other biologics may be of benefit despite a lack of dedicated clinical trials. Ultimately, experimental therapies such as epidermal growth factor enemas, appendectomy or fecal transplantation may be tried before restorative proctocolectomy with J pouch anastomosis, which has demonstrated good results with regards to clinical remission and quality of life.}, }
@article {pmid30060765, year = {2018}, author = {Seal, BS and Drider, D and Oakley, BB and Brüssow, H and Bikard, D and Rich, JO and Miller, S and Devillard, E and Kwan, J and Bertin, G and Reeves, S and Swift, SM and Raicek, M and Gay, CG}, title = {Microbial-derived products as potential new antimicrobials.}, journal = {Veterinary research}, volume = {49}, number = {1}, pages = {66}, pmid = {30060765}, issn = {1297-9716}, mesh = {Animal Diseases/prevention &amp; control ; *Animal Husbandry ; Animals ; Anti-Infective Agents/*analysis ; Bacteriocins ; Bacteriophages ; CRISPR-Cas Systems ; *Drug Discovery ; France ; Livestock ; }, abstract = {Due to the continuing global concerns involving antibiotic resistance, there is a need for scientific forums to assess advancements in the development of antimicrobials and their alternatives that might reduce development and spread of antibiotic resistance among bacterial pathogens. The objectives of the 2[nd] International Symposium on Alternatives to Antibiotics were to highlight promising research results and novel technologies that can provide alternatives to antibiotics for use in animal health and production, assess challenges associated with their authorization and commercialization for use, and provide actionable strategies to support their development. The session on microbial-derived products was directed at presenting novel technologies that included exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials, probiotics development via fecal microbiome transplants among monogastric production animals such as chickens and mining microbial sources such as bacteria or yeast to identify new antimicrobial compounds. Other research has included continuing development of antimicrobial peptides such as newly discovered bacteriocins as alternatives to antibiotics, use of bacteriophages accompanied by development of unique lytic proteins with specific cell-wall binding domains and novel approaches such as microbial-ecology guided discovery of anti-biofilm compounds discovered in marine environments. The symposium was held at the Headquarters of the World Organisation for Animal Health (OIE) in Paris, France during 12-15 December 2016.}, }
@article {pmid30057174, year = {2018}, author = {Jacobson, A and Lam, L and Rajendram, M and Tamburini, F and Honeycutt, J and Pham, T and Van Treuren, W and Pruss, K and Stabler, SR and Lugo, K and Bouley, DM and Vilches-Moure, JG and Smith, M and Sonnenburg, JL and Bhatt, AS and Huang, KC and Monack, D}, title = {A Gut Commensal-Produced Metabolite Mediates Colonization Resistance to Salmonella Infection.}, journal = {Cell host &amp; microbe}, volume = {24}, number = {2}, pages = {296-307.e7}, pmid = {30057174}, issn = {1934-6069}, support = {R01 AI116059/AI/NIAID NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 GM007276/GM/NIGMS NIH HHS/United States ; P50 GM107615/GM/NIGMS NIH HHS/United States ; R01 AI089722/AI/NIAID NIH HHS/United States ; F32 AI133917/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacterial Shedding/physiology ; Bacteroides/physiology ; Cation Transport Proteins/genetics/metabolism ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Host-Pathogen Interactions/*physiology ; Intestinal Diseases/microbiology ; Male ; Mice, Inbred C57BL ; Propionates/*metabolism ; Salmonella Infections/*etiology ; Salmonella typhimurium/*pathogenicity ; }, abstract = {The intestinal microbiota provides colonization resistance against pathogens, limiting pathogen expansion and transmission. These microbiota-mediated mechanisms were previously identified by observing loss of colonization resistance after antibiotic treatment or dietary changes, which severely disrupt microbiota communities. We identify a microbiota-mediated mechanism of colonization resistance against Salmonella enterica serovar Typhimurium (S. Typhimurium) by comparing high-complexity commensal communities with different levels of colonization resistance. Using inbred mouse strains with different infection dynamics and S. Typhimurium intestinal burdens, we demonstrate that Bacteroides species mediate colonization resistance against S. Typhimurium by producing the short-chain fatty acid propionate. Propionate directly inhibits pathogen growth in vitro by disrupting intracellular pH homeostasis, and chemically increasing intestinal propionate levels protects mice from S. Typhimurium. In addition, administering susceptible mice Bacteroides, but not a propionate-production mutant, confers resistance to S. Typhimurium. This work provides mechanistic understanding into the role of individualized microbial communities in host-to-host variability of pathogen transmission.}, }
@article {pmid30055267, year = {2019}, author = {Vaughn, BP and Rank, KM and Khoruts, A}, title = {Fecal Microbiota Transplantation: Current Status in Treatment of GI and Liver Disease.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {2}, pages = {353-361}, doi = {10.1016/j.cgh.2018.07.026}, pmid = {30055267}, issn = {1542-7714}, mesh = {Fecal Microbiota Transplantation/*methods ; Gastrointestinal Diseases/*therapy ; Humans ; Liver Diseases/*therapy ; }, abstract = {Fecal microbiota transplantation was originally introduced as a method to repair intestinal microbiota following failure of multiple treatments of recurrent Clostridiumdifficile infection with antibiotics. However, it is hypothesized that intestinal dysbiosis may contribute to the pathogenesis of many diseases, especially those involving the gastrointestinal tract. Therefore, fecal microbiota transplantation is increasingly being explored as a potential treatment that aims to optimize microbiota composition and functionality. Here, we review the current state of fecal microbiota transplantation development and applications in conditions of greatest interest to a gastroenterologist.}, }
@article {pmid30054112, year = {2019}, author = {Su, HJ and Chiu, YT and Chiu, CT and Lin, YC and Wang, CY and Hsieh, JY and Wei, SC}, title = {Inflammatory bowel disease and its treatment in 2018: Global and Taiwanese status updates.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118}, number = {7}, pages = {1083-1092}, doi = {10.1016/j.jfma.2018.07.005}, pmid = {30054112}, issn = {0929-6646}, mesh = {Databases, Factual ; Global Health ; Humans ; Incidence ; Inflammatory Bowel Diseases/*diagnosis/*epidemiology/*therapy ; Magnetic Resonance Imaging ; National Health Programs ; Positron-Emission Tomography ; Prevalence ; Taiwan/epidemiology ; }, abstract = {The global incidence and prevalence of inflammatory bowel disease (IBD) has increased over the last 2-4 decades, likely because of the adoption of a more "western" lifestyle as well as improved detection and awareness, and Taiwan is no exception. To characterize the increasing burden of IBD, we conducted a comprehensive review of IBD in the existing literature. The following parameters were reviewed: background knowledge and current standard care for IBD, including natural history, epidemiology, pathogenesis, diagnosis, monitoring, and treatment. In addition, new imaging modalities and treatment options such as combined positron emission tomography and magnetic resonance enterography, new biologic agents, small-molecule therapy, biosimilar therapeutics, mesenchymal stem cell transplantation, and fecal microbiota transplantation, all of which have been introduced for IBD management, were reviewed. We also used the hospital-based as well as population-based Taiwan National Health Insurance Research Database to assess Taiwan-specific trends for comparison with global trends.}, }
@article {pmid30052094, year = {2018}, author = {Laing, B and Barnett, MPG and Marlow, G and Nasef, NA and Ferguson, LR}, title = {An update on the role of gut microbiota in chronic inflammatory diseases, and potential therapeutic targets.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {12}, number = {10}, pages = {969-983}, doi = {10.1080/17474124.2018.1505497}, pmid = {30052094}, issn = {1747-4132}, mesh = {Age Factors ; Diet ; Dysbiosis/*complications/*therapy ; Environment ; Exercise ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/immunology/*physiology ; Humans ; Inflammation/*microbiology ; Intestinal Mucosa/immunology/*physiology ; Probiotics/therapeutic use ; }, abstract = {The human microbiome plays a critical role in human health, having metabolic, protective, and trophic functions, depending upon its' exact composition. This composition is affected by a number of factors, including the genetic background of the individual, early life factors (including method of birth, length of breastfeeding) and nature of the diet and other environmental exposures (including cigarette smoking) and general life habits. It plays a key role in the control of inflammation, and in turn, its' composition is significantly influenced by inflammation. Areas covered: We consider metabolic, protective, and trophic functions of the microbiome and influences through the lifespan from post-partum effects, to diet later in life in healthy older adults, the effects of aging on both its' composition, and influence on health and potential therapeutic targets that may have anti-inflammatory effects. Expert commentary: The future will see the growth of more effective therapies targeting the microbiome particularly with respect to the use of specific nutrients and diets personalized to the individual.}, }
@article {pmid30048534, year = {2018}, author = {Jiang, M and Leung, NH and Ip, M and You, JHS}, title = {Cost-effectiveness analysis of ribotype-guided fecal microbiota transplantation in Chinese patients with severe Clostridium difficile infection.}, journal = {PloS one}, volume = {13}, number = {7}, pages = {e0201539}, pmid = {30048534}, issn = {1932-6203}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Asian People ; China/epidemiology ; Clostridioides difficile/classification/*genetics ; Clostridium Infections/economics/epidemiology/*therapy ; Cost-Benefit Analysis ; Decision Support Techniques ; Enterocolitis, Pseudomembranous/economics/epidemiology/*therapy ; Fecal Microbiota Transplantation/*economics/*methods/statistics &amp; numerical data ; Female ; Gene Frequency ; Humans ; Male ; Middle Aged ; *Ribotyping/economics/methods ; Severity of Illness Index ; Survival Rate ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) caused by ribotype 002 strain is associated with poor outcomes in Chinese patients. Fecal microbiota transplantation (FMT) is an effective but costly treatment for CDI. We aimed to examine potential cost-effectiveness of ribotype-guided FMT in Chinese patients with severe CDI.<br><br>METHODS: A decision-analytic model was designed to simulate outcomes of ribotype 002-guided FMT versus vancomycin treatment in Chinese patients with severe CDI in the hospital setting. Outcome measures included mortality rate; direct medical cost; and quality-adjusted life year (QALY) loss for CDI. Sensitivity analysis was performed to examine robustness of base-case results.<br><br>RESULTS: Comparing to vancomycin treatment, ribotype-guided FMT group reduced mortality (11.6% versus 17.1%), cost (USD8,807 versus USD9,790), and saved 0.472 QALYs in base-case analysis. One-way sensitivity analysis found the ribotype-guided FMT group to remain cost-effective when patient acceptance rate of FMT was >0.6% and ribotype 002 prevalence was >0.07%. In probabilistic sensitivity analysis, ribotype-guided FMT gained higher QALYs at 100% of simulations with mean QALY gain of 0.405 QALYs (95%CI: 0.400-0.410; p<0.001). The ribotype-guided group was less costly in 97.9% of time, and mean cost-saving was USA679 (95%CI: 670-688; p<0.001).<br><br>CONCLUSIONS: In the present model, ribotype-guided FMT appears to be a potential option to save QALYs and cost when comparing with vancomycin. The cost-effectiveness of ribotype-guided FMT is subject to the patient acceptance to FMT and prevalence of ribotype 002.}, }
@article {pmid30048425, year = {2018}, author = {Herwaldt, BL and Dougherty, CP and Allen, CK and Jolly, JP and Brown, MN and Yu, P and Yu, Y}, title = {Characteristics of Patients for Whom Benznidazole Was Released Through the CDC-Sponsored Investigational New Drug Program for Treatment of Chagas Disease - United States, 2011-2018.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {67}, number = {29}, pages = {803-805}, pmid = {30048425}, issn = {1545-861X}, mesh = {Adolescent ; Adult ; Aged ; Centers for Disease Control and Prevention, U.S. ; Chagas Disease/*drug therapy/epidemiology ; Child ; Child, Preschool ; Drugs, Investigational/*therapeutic use ; Emigrants and Immigrants/statistics &amp; numerical data ; Female ; Humans ; Infant ; Infant, Newborn ; Latin America/ethnology ; Male ; Middle Aged ; Nitroimidazoles/*therapeutic use ; Trypanocidal Agents/*therapeutic use ; United States/epidemiology ; Young Adult ; }, abstract = {Chagas disease (also known as American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi (1,2). Vectorborne transmission via skin or mucosal contact with the feces of infected triatomine bugs mainly occurs in rural areas of Latin America but has been reported in the southern United States (3). The parasite also is transmissible congenitally and via blood transfusion, organ transplantation, and accidental laboratory exposures. The two drugs used for treating Chagas disease are benznidazole and nifurtimox (1,2), which have been used in Latin America since the 1970s and 1960s, respectively. In the absence of commercially available drugs approved by the Food and Drug Administration (FDA), benznidazole and nifurtimox have been available exclusively through CDC, under Investigational New Drug (IND) treatment protocols. On August 29, 2017, FDA approved a benznidazole product (Chemo Research, SL, in care of Exeltis*) for treatment of Chagas disease (4), which became commercially available on May 14, 2018. Therefore, effective May 14, 2018, benznidazole is no longer available through the CDC-sponsored IND program. This report summarizes selected characteristics of patients for whom CDC released benznidazole through that program from October 2011, when the IND went into effect, until mid-May 2018. The majority of the 365 patients included in intention-to-treat analyses were chronically infected adults who were born and became infected in Latin America. Physician requests for benznidazole should now be directed to the drug company Exeltis.[†] The CDC-sponsored IND for nifurtimox remains in effect to provide an alternative therapeutic option to benznidazole when clinically appropriate. CDC will continue to provide reference diagnostic testing for T. cruzi infection and teleconsultative services regarding Chagas disease.}, }
@article {pmid30047327, year = {2019}, author = {Mogilnicka, I and Ufnal, M}, title = {Gut Mycobiota and Fungal Metabolites in Human Homeostasis.}, journal = {Current drug targets}, volume = {20}, number = {2}, pages = {232-240}, doi = {10.2174/1389450119666180724125020}, pmid = {30047327}, issn = {1873-5592}, mesh = {Animals ; Bacteria/*classification ; Dysbiosis/*microbiology ; Feces/microbiology ; Fungi/*chemistry/physiology ; Gastrointestinal Microbiome ; Homeostasis ; Humans ; Metabolome ; }, abstract = {BACKGROUND: Accumulating evidence suggests that microbiota play an important role in host's homeostasis. Thus far, researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites.<br><br>METHODS: We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis.<br><br>RESULTS: Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases.<br><br>CONCLUSION: The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.}, }
@article {pmid30045880, year = {2019}, author = {Ren, Z and Li, A and Jiang, J and Zhou, L and Yu, Z and Lu, H and Xie, H and Chen, X and Shao, L and Zhang, R and Xu, S and Zhang, H and Cui, G and Chen, X and Sun, R and Wen, H and Lerut, JP and Kan, Q and Li, L and Zheng, S}, title = {Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma.}, journal = {Gut}, volume = {68}, number = {6}, pages = {1014-1023}, pmid = {30045880}, issn = {1468-3288}, mesh = {Biomarkers, Tumor/*analysis ; Carcinoma, Hepatocellular/drug therapy/*pathology ; Case-Control Studies ; China ; DNA Mutational Analysis ; Drug Delivery Systems ; Dysbiosis/microbiology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Liver Cirrhosis/drug therapy/*pathology ; Liver Neoplasms/drug therapy/*pathology ; Male ; Polymerase Chain Reaction/methods ; Reference Values ; Reproducibility of Results ; Risk Assessment ; }, abstract = {OBJECTIVE: To characterise gut microbiome in patients with hepatocellular carcinoma (HCC) and evaluate the potential of microbiome as non-invasive biomarkers for HCC.<br><br>DESIGN: We collected 486 faecal samples from East China, Central China and Northwest China prospectively and finally 419 samples completed Miseq sequencing. We characterised gut microbiome, identified microbial markers and constructed HCC classifier in 75 early HCC, 40 cirrhosis and 75 healthy controls. We validated the results in 56 controls, 30 early HCC and 45 advanced HCC. We further verified diagnosis potential in 18 HCC from Xinjiang and 80 HCC from Zhengzhou.<br><br>RESULTS: Faecal microbial diversity was increased from cirrhosis to early HCC with cirrhosis. Phylum Actinobacteria was increased in early HCC versus cirrhosis. Correspondingly, 13 genera including Gemmiger and Parabacteroides were enriched in early HCC versus cirrhosis. Butyrate-producing genera were decreased, while genera producing-lipopolysaccharide were increased in early HCC versus controls. The optimal 30 microbial markers were identified through a fivefold cross-validation on a random forest model and achieved an area under the curve of 80.64% between 75 early HCC and 105 non-HCC samples. Notably, gut microbial markers validated strong diagnosis potential for early HCC and even advanced HCC. Importantly, microbial markers successfully achieved a cross-region validation of HCC from Northwest China and Central China.<br><br>CONCLUSIONS: This study is the first to characterise gut microbiome in patients with HCC and to report the successful diagnosis model establishment and cross-region validation of microbial markers for HCC. Gut microbiota-targeted biomarkers represent potential non-invasive tools for early diagnosis of HCC.}, }
@article {pmid30039794, year = {2018}, author = {Bruno, G and Trentino, P and Viarengo, MA and Toma, A and Virili, C and Centanni, M and Picarelli, A and Gozzo, P and Accarpio, F and Porowska, B}, title = {Sporadic pedunculated duodenal adenomas. Clinical presentations and endoscopic management: a case series.}, journal = {Il Giornale di chirurgia}, volume = {39}, number = {4}, pages = {248-254}, pmid = {30039794}, issn = {0391-9005}, mesh = {Acute Disease ; Adenoma/complications/pathology/*surgery ; Aged ; Duodenal Neoplasms/complications/pathology/*surgery ; Duodenoscopy/*methods ; Female ; Gastrointestinal Hemorrhage/etiology ; Gastroscopy/*methods ; Hemostasis, Surgical/methods ; Humans ; Malabsorption Syndromes/etiology ; Male ; Middle Aged ; Pancreatitis/*etiology ; Peristalsis ; Thyroxine/administration &amp; dosage/pharmacokinetics ; }, abstract = {The prevalence of sporadic duodenal polyps is estimated to be 0.3%-4.6% in patients referred for an upper endoscopy. Most of patients are asymptomatic (66-80%) at the time of diagnosis though bleeding, anemia and abdominal pain are the most commonly reported symptoms. These are related to the polyp's size, location and histological characteristics. We describe three cases of big, pedunculated nonampullary sporadic duodenal polyps (tubulovillous low-grade dysplasia adenomas) located in the second part of the duodenum and characterized by different clinical presentations, managed in our Endoscopic Unit within one year (between 2016 and 2017). Polypectomies were performed, either piece-meal or en-bloc using various endoscopic instruments. In one of our patients (case 1), a delayed bleeding (36 hours after the procedure) occurred eventually managed conservatively with two units of blood transfusion. In the same patient, in the following months after polypectomy, the pre-procedural state of anemia misclassified as Mediterranean anemia has improved with a significant rise of hemoglobin value (14.1g/dl). In a patient who previously underwent a renal transplant (case 2), endoscopy was indicated, based on the positive fecal occult blood test. In another patient (case 3), a big polyp induced pancreatitis since it exerted a strong traction on the duodenal wall during peristaltic movements. The removal of the polyp has led to the resolution of pancreatitis and associated symptoms.}, }
@article {pmid30038469, year = {2018}, author = {Iannone, A and Giorgio, F and Russo, F and Riezzo, G and Girardi, B and Pricci, M and Palmer, SC and Barone, M and Principi, M and Strippoli, GF and Di Leo, A and Ierardi, E}, title = {New fecal test for non-invasive Helicobacter pylori detection: A diagnostic accuracy study.}, journal = {World journal of gastroenterology}, volume = {24}, number = {27}, pages = {3021-3029}, pmid = {30038469}, issn = {2219-2840}, mesh = {Adult ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Breath Tests/methods ; Clarithromycin/pharmacology/therapeutic use ; Cross-Sectional Studies ; DNA, Bacterial/genetics/isolation &amp; purification ; Drug Resistance, Bacterial/*genetics ; Feces/*chemistry ; Female ; Helicobacter Infections/*diagnosis/drug therapy/microbiology ; Helicobacter pylori/genetics/*isolation &amp; purification ; Humans ; Levofloxacin/pharmacology/therapeutic use ; Male ; Middle Aged ; Point Mutation ; Predictive Value of Tests ; Prospective Studies ; Reference Standards ; Sensitivity and Specificity ; }, abstract = {AIM: To assess the diagnostic accuracy of a new fecal test for detecting Helicobacter pylori (H. pylori), using[13]C-urea breath test as the reference standard, and explore bacterial antibiotic resistance.<br><br>METHODS: We conducted a prospective two-center diagnostic test accuracy study. We enrolled consecutive people&#x2265; 18 years without previous diagnosis of H. pylori infection, referred for dyspepsia between February and October 2017. At enrollment, all participants underwent [13]C-urea breath test. Participants aged over 50 years were scheduled to undergo upper endoscopy with histology. Participants collected stool samples 1-3 d after enrollment for a new fecal investigation (THD fecal test). The detection of bacterial 23S rRNA subunit gene indicated H. pylori infection. We also used the index diagnostic test to examine mutations conferring resistance to clarithromycin and levofloxacin. Independent investigators analyzed index test and reference test standard results blinded to the other test findings. We estimated sensitivity, specificity, positive (PPV) and negative (NPV) predictive value, diagnostic accuracy, positive and negative likelihood ratio (LR), together with 95% confidence intervals (CI).<br><br>RESULTS: We enrolled 294 consecutive participants (age: Median 37.0 years, IQR: 29.0-46.0 years; men: 39.8%). Ninety-five (32.3%) participants had a positive[13]C-urea breath test. Twenty-three (7.8%) participants underwent upper endoscopy with histology, with a full concordance between [13]C-urea breath test and histology in detecting H. pylori infection. Four (1.4%) out of the 294 participants withdrew from the study after the enrollment visit and did not undergo THD fecal testing. In the 290 participants who completed the study, the THD fecal test sensitivity was 90.2% (CI: 84.2%-96.3%), specificity 98.5% (CI:96.8%-100%), PPV 96.5% (CI: 92.6%-100%), NPV 95.6% (CI: 92.8%-98.4%), accuracy 95.9% (CI: 93.6%-98.2%), positive LR 59.5(CI: 19.3-183.4), negative LR 0.10 (CI: 0.05-0.18). Out of 83 infected participants identified with the THD fecal test, 34 (41.0%) had bacterial genotypic changes consistent with antibiotic-resistant H. pylori infection. Of these, 27 (32.5%) had bacterial strains resistant to clarithromycin, 3 (3.6%) to levofloxacin, and 4 (4.8%) to both antibiotics.<br><br>CONCLUSION: The THD fecal test has high performance for the non-invasive diagnosis of H. pylori infection while additionally enabling the assessment of bacterial antibiotic resistances.}, }
@article {pmid30036559, year = {2018}, author = {Todt, D and Moeller, N and Praditya, D and Kinast, V and Friesland, M and Engelmann, M and Verhoye, L and Sayed, IM and Behrendt, P and Dao Thi, VL and Meuleman, P and Steinmann, E}, title = {The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo.}, journal = {Antiviral research}, volume = {157}, number = {}, pages = {151-158}, pmid = {30036559}, issn = {1872-9096}, mesh = {Aglaia/chemistry ; Animals ; Antiviral Agents/administration &amp; dosage/isolation &amp; purification/*pharmacology ; Cells, Cultured ; Disease Models, Animal ; Drug Interactions ; Feces/virology ; Hepatitis E/*drug therapy ; Hepatitis E virus/*drug effects/growth &amp; development ; Humans ; Mice ; Ribavirin/pharmacology ; Triterpenes/administration &amp; dosage/isolation &amp; purification/*pharmacology ; Viral Load ; Virus Replication/*drug effects ; }, abstract = {Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. HEV infections are the common cause of acute hepatitis but can also take chronic courses. Ribavirin is the treatment of choice for most patients and type I interferon (IFN) has been evaluated in a few infected transplantation patients in vivo. However, no effective and specific treatments against HEV infections are currently available. In this study, we evaluated the natural compound silvestrol, isolated from the plant Aglaia foveolata, and known for its specific inhibition of the DEAD-box RNA helicase eIF4A in state-of-the-art HEV experimental model systems. Silvestrol blocked HEV replication of different subgenomic replicons in a dose-dependent manner at low nanomolar concentrations and acted additive to ribavirin (RBV). In addition, HEV p6-based full length replication and production of infectious particles was reduced in the presence of silvestrol. A pangenotypic effect of the compound was further demonstrated with primary isolates from four different human genotypes in HEV infection experiments of hepatocyte-like cells derived from human embryonic and induced pluripotent stem cells. In vivo, HEV RNA levels rapidly declined in the feces of treated mice while no effect was observed in the vehicle treated control animals. In conclusion, silvestrol could be identified as pangenotypic HEV replication inhibitor in vitro with additive effect to RBV and further demonstrated high potency in vivo. The compound therefore may be considered in future treatment strategies of chronic hepatitis E in immunocompromised patients.}, }
@article {pmid30034913, year = {2017}, author = {Zhou, Z and Zhong, W}, title = {Targeting the gut barrier for the treatment of alcoholic liver disease.}, journal = {Liver research (Beijing, China)}, volume = {1}, number = {4}, pages = {197-207}, pmid = {30034913}, issn = {2096-2878}, support = {P30 DK056350/DK/NIDDK NIH HHS/United States ; R01 AA018844/AA/NIAAA NIH HHS/United States ; R01 AA020212/AA/NIAAA NIH HHS/United States ; }, abstract = {Alcohol consumption remains one of the predominant causes of liver disease and liver-related death worldwide. Intriguingly, dysregulation of the gut barrier is a key factor promoting the pathogenesis of alcoholic liver disease (ALD). A functional gut barrier, which consists of a mucus layer, an intact epithelial monolayer and mucosal immune cells, supports nutrient absorption and prevents bacterial penetration. Compromised gut barrier function is associated with the progression of ALD. Indeed, alcohol consumption disrupts the gut barrier, increases gut permeability, and induces bacterial translocation both in ALD patients and in experimental models with ALD. Moreover, alcohol consumption also causes enteric dysbiosis with both numerical and proportional perturbations. Here, we review and discuss mechanisms of alcohol-induced gut barrier dysfunction to better understand the contribution of the gut-liver axis to the pathogenesis of ALD. Unfortunately, there is no effectual Food and Drug Administration-approved treatment for any stage of ALD. Therefore, we conclude with a discussion of potential strategies aimed at restoring the gut barrier in ALD. The principle behind antibiotics, prebiotics, probiotics and fecal microbiota transplants is to restore microbial symbiosis and subsequently gut barrier function. Nutrient-based treatments, such as dietary supplementation with zinc, niacin or fatty acids, have been shown to regulate tight junction expression, reduce intestinal inflammation, and prevent endotoxemia as well as liver injury caused by alcohol in experimental settings. Interestingly, saturated fatty acids may also directly control the gut microbiome. In summary, clinical and experimental studies highlight the significance and efficacy of the gut barrier in treating ALD.}, }
@article {pmid30031742, year = {2018}, author = {Klein, T and Winkler, A and Vahdad, RM and Ekamp, A and Boemers, TM}, title = {The Cologne pouch procedure for continent anal urinary diversion in children with bladder exstrophy-epispadias complex.}, journal = {Journal of pediatric urology}, volume = {14}, number = {5}, pages = {431.e1-431.e6}, doi = {10.1016/j.jpurol.2018.06.007}, pmid = {30031742}, issn = {1873-4898}, mesh = {Anal Canal/*surgery ; Anastomosis, Surgical/methods ; Bladder Exstrophy/*surgery ; Child ; Child, Preschool ; Colon, Sigmoid/transplantation ; Epispadias/*surgery ; Female ; Humans ; Infant ; Male ; Retrospective Studies ; Treatment Outcome ; Urinary Bladder/*surgery ; Urinary Diversion/methods ; *Urinary Reservoirs, Continent ; }, abstract = {INTRODUCTION: In children who remain incontinent after reconstruction of bladder exstrophy-epispadias complex (BEEC), continent anal urinary diversion (CAD) is one option to achieve continence. Known problems after CAD are an increased stool frequency and ureterointestinal stenosis. We devised a new surgical technique of CAD that we named the "Cologne pouch procedure" (CPP) that renders the possibility of separate evacuation of urine and feces. Furthermore, we connect the bladder plate to the rectosigmoid pouch instead of performing a ureterosigmoidostomy to reduce the rate of ureterointestinal stenosis. In this study, we want to introduce the CCP and critically evaluate our results.<br><br>STUDY DESIGN: In CPP a detubularized sigmoid-bladder pouch is created, which is naturally connected to the rectum. A retrospective study was performed including all patients with BEEC and CPP treated in our hospital between January 1, 2007, and December 31, 2016. Epidemiological and surgical key data, complications, and the need for alkaline supplementation were assessed. At follow-up examinations, we evaluated continence, ability of independent urine and feces evacuation, need for bicarbonate supplementation, status of the upper urinary tract, and complications such as urinary tract infections or urolithiasis.<br><br>RESULTS: In total, 29 patients with BEEC and CPP were included. The mean age at surgery was 4.2&#xa0;&#xb1;&#xa0;3.3 years (range 0.1-12.7 years). Overall, 14 short-term complications occurred in nine patients. Postoperatively, all patients were continent for urine and feces during daytime and only one child occasionally lost small portions of urine at night. An independent evacuation of urine and feces was accomplished in 22 patients (81.5%). Continued bicarbonate supplementation was necessary in 15 patients (55.6%). During the follow-up period six patients (22.2%) had a single urinary tract infection and four patients (14.8%) calculi of the urinary tract. No urinary tract abnormalities-especially no vesicoureteral reflux (VUR) or stenosis-were detected during follow-up ultrasound examination. In two children, a preoperatively known hydronephrosis decreased after CPP.<br><br>CONCLUSION: CPP is a novel technique that yields excellent results concerning continence. In contrast to other forms of rectosigmoid urinary diversion, functional separation of defecation and urination can be achieved in most patients.}, }
@article {pmid30031625, year = {2019}, author = {Leclercq, S and Stärkel, P and Delzenne, NM and de Timary, P}, title = {The gut microbiota: A new target in the management of alcohol dependence?.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {74}, number = {}, pages = {105-111}, doi = {10.1016/j.alcohol.2018.03.005}, pmid = {30031625}, issn = {1873-6823}, mesh = {Alcoholism/diet therapy/*microbiology/psychology ; Animals ; Brain/physiology ; Ethanol/toxicity ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Intestinal Mucosa/drug effects/metabolism ; Prebiotics ; Probiotics/pharmacology ; }, abstract = {The gastrointestinal tract is the natural habitat for a huge community of microorganisms, comprising bacteria, viruses, fungi and yeast. This microbial ecosystem codevelops with the host throughout life and is subject to a complex interplay that depends on multiple factors including host genetics, nutrition, life-style, stress, diseases and antibiotics use. The gut microbiota, that refers to intestinal bacteria, has profound influence on the host immune system, metabolism and nervous system. Indeed, intestinal bacteria supply the host with essential nutrients such as vitamins, metabolize bile acids and undigested compounds, defend against pathogen invasion, participate to the development of the intestinal architecture and the intestinal immune system and play an important role in the maintenance of the gut barrier function. More recently, the gut microbiota has been shown to influence brain functions, such as myelin synthesis, the blood-brain barrier permeability and neuroinflammatory responses but also mood and behavior. The cross-talk between microbes and the host implicates a vast array of signaling pathways that involve many different classes of molecules like metabolites produced by the bacteria from dietary or endogenous sources of carbohydrates and proteins (i.e. short-chain fatty acids (SCFAs), indole), neurotransmitters and inflammatory cytokines. This review will focus on the involvement of the gut microbiota in the pathophysiological aspects of alcohol dependence related to the gut barrier function, liver damage and psychological disturbances. We will also discuss the possibility to create new and realistic humanized animal models of alcohol dependence by the use of fecal transplantation.}, }
@article {pmid30029989, year = {2018}, author = {Gianotti, L and Besselink, MG and Sandini, M and Hackert, T and Conlon, K and Gerritsen, A and Griffin, O and Fingerhut, A and Probst, P and Abu Hilal, M and Marchegiani, G and Nappo, G and Zerbi, A and Amodio, A and Perinel, J and Adham, M and Raimondo, M and Asbun, HJ and Sato, A and Takaori, K and Shrikhande, SV and Del Chiaro, M and Bockhorn, M and Izbicki, JR and Dervenis, C and Charnley, RM and Martignoni, ME and Friess, H and de Pretis, N and Radenkovic, D and Montorsi, M and Sarr, MG and Vollmer, CM and Frulloni, L and Büchler, MW and Bassi, C}, title = {Nutritional support and therapy in pancreatic surgery: A position paper of the International Study Group on Pancreatic Surgery (ISGPS).}, journal = {Surgery}, volume = {164}, number = {5}, pages = {1035-1048}, doi = {10.1016/j.surg.2018.05.040}, pmid = {30029989}, issn = {1532-7361}, mesh = {Consensus ; Enzyme Replacement Therapy/methods ; Evidence-Based Medicine/methods/standards ; Exocrine Pancreatic Insufficiency/diagnosis/etiology/metabolism/*therapy ; Feces/chemistry ; Humans ; Malnutrition/diagnosis/etiology/metabolism/*therapy ; Nutritional Status ; Nutritional Support/*methods/standards ; Pancreatic Elastase/analysis ; Pancreatic Fistula/diagnosis/etiology/metabolism/therapy ; Pancreaticoduodenectomy/*adverse effects ; Perioperative Care/methods/standards ; Postoperative Complications/diagnosis/etiology/metabolism/*therapy ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: The optimal nutritional therapy in the field of pancreatic surgery is still debated.<br><br>METHODS: An international panel of recognized pancreatic surgeons and pancreatologists decided that the topic of nutritional support was of importance in pancreatic surgery. Thus, they reviewed the best contemporary literature and worked to develop a position paper to provide evidence supporting the integration of appropriate nutritional support into the overall management of patients undergoing pancreatic resection. Strength of recommendation and quality of evidence were based on the approach of the grading of recommendations assessment, development and evaluation Working Group.<br><br>RESULTS: The measurement of nutritional status should be part of routine preoperative assessment because malnutrition is a recognized risk factor for surgery-related complications. In addition to patient's weight loss and body mass index, measurement of sarcopenia and sarcopenic obesity should be considered in the preoperative evaluation because they are strong predictors of poor short-term and long-term outcomes. The available data do not show any definitive nutritional advantages for one specific type of gastrointestinal reconstruction technique after pancreatoduodenectomy over the others. Postoperative early resumption of oral intake is safe and should be encouraged within enhanced recovery protocols, but in the case of severe postoperative complications or poor tolerance of oral food after the operation, supplementary artificial nutrition should be started at once. At present, there is not enough evidence to show the benefit of avoiding oral intake in clinically stable patients who are complicated by a clinically irrelevant postoperative pancreatic fistula (a so-called biochemical leak), while special caution should be given to feeding patients with clinically relevant postoperative pancreatic fistula orally. When an artificial nutritional support is needed, enteral nutrition is preferred whenever possible over parenteral nutrition. After the operation, regardless of the type of pancreatic resection or technique of reconstruction, patients should be monitored carefully to assess for the presence of endocrine and exocrine pancreatic insufficiency. Although fecal elastase-1 is the most readily available clinical test for detection of pancreatic exocrine insufficiency, its sensitivity and specificity are low. Pancreatic enzyme replacement therapy should be initiated routinely after pancreatoduodenectomy and in patients with locally advanced disease and continued for at least 6 months after surgery, because untreated pancreatic exocrine insufficiency may result in severe nutritional derangement.<br><br>CONCLUSION: The importance of this position paper is the consensus reached on the topic. Concentrating on nutritional support and therapy is of utmost value in pancreatic surgery for both short- and long-term outcomes.}, }
@article {pmid30025704, year = {2018}, author = {McDonald, JAK and Mullish, BH and Pechlivanis, A and Liu, Z and Brignardello, J and Kao, D and Holmes, E and Li, JV and Clarke, TB and Thursz, MR and Marchesi, JR}, title = {Inhibiting Growth of Clostridioides difficile by Restoring Valerate, Produced by the Intestinal Microbiota.}, journal = {Gastroenterology}, volume = {155}, number = {5}, pages = {1495-1507.e15}, pmid = {30025704}, issn = {1528-0012}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; MR/L009226/1/MRC_/Medical Research Council/United Kingdom ; 107660/Z/15Z/WT_/Wellcome Trust/United Kingdom ; P62104/MRC_/Medical Research Council/United Kingdom ; MR/P028225/1/MRC_/Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; MR/P002536/1/MRC_/Medical Research Council/United Kingdom ; EME/13/121/07/DH_/Department of Health/United Kingdom ; }, mesh = {Animals ; Bile Acids and Salts/analysis ; Chromatography, High Pressure Liquid ; Clindamycin/pharmacology ; Clostridioides difficile/*drug effects/growth &amp; development ; Clostridium Infections/*therapy ; Feces/chemistry ; Female ; Gas Chromatography-Mass Spectrometry ; *Gastrointestinal Microbiome ; Magnetic Resonance Spectroscopy ; Mice, Inbred C57BL ; Spores, Bacterial ; Triglycerides/therapeutic use ; Valerates/metabolism/*pharmacology ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is effective for treating recurrent Clostridioides difficile infection (CDI), but there are concerns about its long-term safety. Understanding the mechanisms of the effects of FMT could help us design safer, targeted therapies. We aimed to identify microbial metabolites that are important for C difficile growth.<br><br>METHODS: We used a CDI chemostat model as a tool to study the effects of FMT in&#xa0;vitro. The following analyses were performed: C difficile plate counts,&#xa0;16S rRNA gene sequencing, proton nuclear magnetic resonance spectroscopy, and ultra-performance liquid chromatography and mass spectrometry bile acid profiling. FMT mixtures were prepared using fresh fecal samples provided by donors enrolled in an FMT program in the United Kingdom. Results from chemostat experiments were validated using human stool samples, C difficile batch cultures, and C57BL/6 mice with CDI. Human stool samples were collected from 16 patients with recurrent CDI and healthy donors (n&#xa0;= 5) participating in an FMT trial in Canada.<br><br>RESULTS: In the CDI chemostat model, clindamycin decreased valerate and deoxycholic acid concentrations and increased C difficile total viable counts and valerate precursors, taurocholic acid, and succinate concentrations. After we stopped adding clindamycin, levels of bile acids and succinate recovered, whereas levels of valerate and valerate precursors did not. In the CDI chemostat model, FMT increased valerate concentrations and decreased C difficile total viable counts (94% decrease), spore counts (86% decrease), and valerate precursor concentrations; concentrations of bile acids were unchanged. In stool samples from patients with CDI, valerate was depleted before FMT but restored after FMT. Clostridioides difficile batch cultures confirmed that valerate decreased vegetative growth, and that taurocholic acid was required for germination but had no effect on vegetative growth. Clostridioides difficile total viable&#xa0;counts were decreased by 95% in mice with CDI given&#xa0;glycerol trivalerate compared with phosphate buffered saline.<br><br>CONCLUSIONS: We identified valerate as a metabolite that is depleted with clindamycin and only recovered with FMT. Valerate is a target for a rationally designed recurrent CDI therapy.}, }
@article {pmid30014799, year = {2018}, author = {Kota, RK and Ambati, RR and Y V V, AK and Srirama, K and Reddy, PN}, title = {Recent Advances in Probiotics as Live Biotherapeutics Against Gastrointestinal Diseases.}, journal = {Current pharmaceutical design}, volume = {24}, number = {27}, pages = {3162-3171}, doi = {10.2174/1381612824666180717105128}, pmid = {30014799}, issn = {1873-4286}, mesh = {Animals ; Gastrointestinal Diseases/*drug therapy ; Humans ; Probiotics/*therapeutic use ; }, abstract = {BACKGROUND: Gastrointestinal (GI) diseases are a major cause of emergency department visits requiring hospitalizations leading to considerable burden on global economy. Several factors contribute to the onset of gastrointestinal diseases such as pathogens (parasites, bacteria, virus, toxins etc.), autoimmune disorders and severe inflammation of intestine.<br><br>OBJECTIVE: One common feature among all these diseases is the dysentery and alteration of gut microbiota composition (gut dysbiosis). Apart from conventional therapies such as antibiotics and ORS supplementation, gut microbiota modulation with probiotic supplementation has emerged as a successful and healthy alternative in mitigating GI diseases. In this review our goal is to discuss the causes of gastrointestinal diseases and the present state of various therapeutic strategies such as probiotics as live biotherapeutics and Fecal Microbial Transplants (FMT's).<br><br>CONCLUSION: Several reports and clinical trials point out to the beneficial effects of probiotics in modulating the gut microbiota and improving the side effects of gastrointestinal diseases. Live biotherapeutics and FMT's could be suitable and successful alternatives to conventional therapies in mitigating the gastrointestinal pathogens.}, }
@article {pmid30011107, year = {2018}, author = {Lin, SC and Alonso, CD and Moss, AC}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with solid organ transplants: an institutional experience and review of the literature.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {20}, number = {6}, pages = {e12967}, doi = {10.1111/tid.12967}, pmid = {30011107}, issn = {1399-3062}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Bacterial Toxins/isolation &amp; purification ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/microbiology/*therapy ; Colonoscopy/methods ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Humans ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Pancreas Transplantation/*adverse effects ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridium difficile, an anaerobic gram-positive, spore-forming bacillus, has become the most common cause of nosocomial infectious diarrhea, and is associated with increased mortality in all populations. Patients who have received solid organ transplants (SOT) are at increased risk of Clostridium difficile infection (CDI) and CDI recurrence (rCDI). This may be related to chronic immunosuppression, frequent antibiotic exposure, and increased or prolonged hospitalizations. Increased morbidity and mortality from CDI is well-described in SOT patients. Conventional treatments for index and recurrent CDI include vancomycin and fidaxomicin. Fecal microbiota transplantation has emerged as an effective and safe alternative for treating rCDI in the general population. Reports of its safety in certain immunocompromised populations, such as those with inflammatory bowel disease, appear reassuring, but outcomes among SOT patients are less well known. Here, we summarize the experiences published to date on the treatment of rCDI with FMT in SOT patient, and also describe our detailed FMT protocol and experience in treating a series of SOT patients with rCDI. In addition to reporting the safety and efficacy of our FMT experience, we also discuss the diagnostic challenges and considerations in this population of solid organ transplant recipients.}, }
@article {pmid30010747, year = {2018}, author = {Nusbaum, DJ and Sun, F and Ren, J and Zhu, Z and Ramsy, N and Pervolarakis, N and Kunde, S and England, W and Gao, B and Fiehn, O and Michail, S and Whiteson, K}, title = {Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, pmid = {30010747}, issn = {1574-6941}, support = {R01 GM120624/GM/NIGMS NIH HHS/United States ; R56 HL126754/HL/NHLBI NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; R01 HD081197/HD/NICHD NIH HHS/United States ; T32 EB009418/EB/NIBIB NIH HHS/United States ; }, mesh = {Child ; Clostridiaceae/classification/genetics/*isolation &amp; purification ; Colitis, Ulcerative/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Metabolomics ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Ulcerative colitis is a chronic inflammatory disease of the colon that carries a significant disease burden in children. Therefore, new therapeutic approaches are being explored to help children living with this disease. Fecal microbiota transplantation (FMT) has been successful in some children with ulcerative colitis. However, the mechanism of its therapeutic effect in this patient population is not well understood. To characterize changes in gut microbial and metabolomic profiles after FMT, we performed 16S rRNA gene sequencing, shotgun metagenomic sequencing, virome analysis and untargeted metabolomics by gas chromatography-time of flight-mass spectrometry on stool samples collected before and after FMT from four children with ulcerative colitis who responded to this treatment. Alpha diversity of the gut microbiota increased after intervention, with species richness rising from 251 (S.D. 125) to 358 (S.D. 27). In responders, the mean relative abundance of bacteria in the class Clostridia shifted toward donor levels, increasing from 33% (S.D. 11%) to 54% (S.D. 16%). Patient metabolomic and viromic profiles exhibited a similar but less pronounced shift toward donor profiles after FMT. The fecal concentrations of several metabolites were altered after FMT, correlating with clinical improvement. Larger studies using a similar multi-omics approach may suggest novel strategies for the treatment of pediatric ulcerative colitis.}, }
@article {pmid30010734, year = {2018}, author = {Geng, S and Cheng, S and Li, Y and Wen, Z and Ma, X and Jiang, X and Wang, Y and Han, X}, title = {Faecal Microbiota Transplantation Reduces Susceptibility to Epithelial Injury and Modulates Tryptophan Metabolism of the Microbial Community in a Piglet Model.}, journal = {Journal of Crohn's &amp; colitis}, volume = {12}, number = {11}, pages = {1359-1374}, doi = {10.1093/ecco-jcc/jjy103}, pmid = {30010734}, issn = {1876-4479}, mesh = {Animals ; Colitis/chemically induced/pathology/*prevention &amp; control ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Homeostasis ; Indoleacetic Acids/metabolism ; Interleukins/metabolism ; Intestinal Mucosa/metabolism/*pathology ; Lipopolysaccharides ; Mass Spectrometry ; Metabolome ; RNA, Ribosomal, 16S/analysis ; Receptors, Aryl Hydrocarbon/metabolism ; Swine ; Tryptophan/*metabolism ; Interleukin-22 ; }, abstract = {BACKGROUND AND AIMS: Faecal microbiota transplantation [FMT] has shown promise as a treatment for inflammatory bowel disease [IBD]. Using a piglet model, our previous study indicated that exogenous faecal microbiota can increase the expressions of tight junction proteins, mucin and antimicrobial peptide in the intestinal mucosa, suggesting a beneficial effect of FMT on gut barrier and gastrointestinal health. However, specific connections between FMT-induced microbial changes and modulation of the intestinal barrier remain to be fully illustrated. Here, we aimed to determine the potential role of metabolic function of gut microbiota in the beneficial effects of FMT.<br><br>METHODS: The influence of FMT on the maintenance of intestinal homeostasis was assessed by early-life gut microbiota intervention on newborn piglets and subsequent lipopolysaccharide [LPS] challenge. Analysis of the gut microbiome and metabolome was carried out by 16S rRNA gene sequencing and multiple mass spectrometry platforms.<br><br>RESULTS: FMT modulated the diversity and composition of colonic microbiota and reduced the susceptibility to LPS-induced destruction of epithelial integrity and severe inflammatory response. Metabolomic analysis revealed functional changes of the gut metabolome along with a significant increase of the typical microbiota-derived tryptophan catabolite indole-3-acetic acid in the colonic lumen. In concordance with the metabolome data, metagenomics prediction analysis based on 16S rRNA gene sequencing also demonstrated that FMT modulated the metabolic functions of gut microbiota associated with indole alkaloid biosynthesis, cytochrome P450 and intestinal homeostasis, which coincided with up-regulation of cytokine interleukin-22 and enhanced activation of aryl hydrocarbon receptor in the recipient colon.<br><br>CONCLUSIONS: Our data reveal a regulatory effect of FMT on tryptophan metabolism of gut microbiota in the recipient colon, which may play a potential role in maintenance of the intestinal barrier.}, }
@article {pmid30009869, year = {2018}, author = {Cheminet, G and Kapel, N and Bleibtreu, A and Sadou Yayé, H and Bellanger, A and Duval, X and Joly, F and Fantin, B and de Lastours, V and , }, title = {Faecal microbiota transplantation with frozen capsules for relapsing Clostridium difficile infections: the first experience from 15 consecutive patients in France.}, journal = {The Journal of hospital infection}, volume = {100}, number = {2}, pages = {148-151}, doi = {10.1016/j.jhin.2018.07.005}, pmid = {30009869}, issn = {1532-2939}, mesh = {Adult ; Aged ; Aged, 80 and over ; Capsules/*administration &amp; dosage ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; France ; Humans ; Male ; Middle Aged ; Secondary Prevention ; Treatment Outcome ; }, }
@article {pmid30007918, year = {2019}, author = {Wu, TR and Lin, CS and Chang, CJ and Lin, TL and Martel, J and Ko, YF and Ojcius, DM and Lu, CC and Young, JD and Lai, HC}, title = {Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis.}, journal = {Gut}, volume = {68}, number = {2}, pages = {248-262}, doi = {10.1136/gutjnl-2017-315458}, pmid = {30007918}, issn = {1468-3288}, mesh = {Animals ; *Ascomycota ; Bacteroidetes/*drug effects/*physiology ; Diabetes Mellitus, Type 2/*prevention &amp; control ; Diet, High-Fat ; Fecal Microbiota Transplantation ; Fungal Polysaccharides/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Weight ; Obesity/*prevention &amp; control ; Prebiotics ; Symbiosis ; }, abstract = {OBJECTIVE: The medicinal fungus Ophiocordyceps sinensis and its anamorph Hirsutella sinensis have a long history of use in traditional Chinese medicine for their immunomodulatory properties. Alterations of the gut microbiota have been described in obesity and type 2 diabetes. We examined the possibility that H. sinensis mycelium (HSM) and isolated fractions containing polysaccharides may prevent diet-induced obesity and type 2 diabetes by modulating the composition of the gut microbiota.<br><br>DESIGN: High-fat diet (HFD)-fed mice were treated with HSM or fractions containing polysaccharides of different molecular weights. The effects of HSM and polysaccharides on the gut microbiota were assessed by horizontal faecal microbiota transplantation (FMT), antibiotic treatment and 16S rDNA-based microbiota analysis.<br><br>RESULTS: Fraction H1 containing high-molecular weight polysaccharides (>300&#x2009;kDa) considerably reduced body weight gain (&#x223c;50% reduction) and metabolic disorders in HFD-fed mice. These effects were associated with increased expression of thermogenesis protein markers in adipose tissues, enhanced gut integrity, reduced intestinal and systemic inflammation and improved insulin sensitivity and lipid metabolism. Gut microbiota analysis revealed that H1 polysaccharides selectively promoted the growth of Parabacteroides goldsteinii, a commensal bacterium whose level was reduced in HFD-fed mice. FMT combined with antibiotic treatment showed that neomycin-sensitive gut bacteria negatively correlated with obesity traits and were required for H1's anti-obesogenic effects. Notably, oral treatment of HFD-fed mice with live P. goldsteinii reduced obesity and was associated with increased adipose tissue thermogenesis, enhanced intestinal integrity and reduced levels of inflammation and insulin resistance.<br><br>CONCLUSIONS: HSM polysaccharides and the gut bacterium P. goldsteinii represent novel prebiotics and probiotics that may be used to treat obesity and type 2 diabetes.}, }
@article {pmid30004130, year = {2018}, author = {Inserra, A and Rogers, GB and Licinio, J and Wong, ML}, title = {The Microbiota-Inflammasome Hypothesis of Major Depression.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {40}, number = {9}, pages = {e1800027}, doi = {10.1002/bies.201800027}, pmid = {30004130}, issn = {1521-1878}, mesh = {Animals ; Depressive Disorder, Major/*metabolism/*pathology ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammasomes/*metabolism ; Inflammation/metabolism/microbiology ; Metabolic Networks and Pathways/physiology ; Signal Transduction/physiology ; }, abstract = {We propose the "microbiota-inflammasome" hypothesis of major depressive disorder (MDD, a mental illness affecting the way a person feels and thinks, characterized by long-lasting feelings of sadness). We hypothesize that pathological shifts in gut microbiota composition (dysbiosis) caused by stress and gut conditions result in the upregulation of pro-inflammatory pathways mediated by the Nod-like receptors family pyrin domain containing 3 (NLRP3) inflammasome (an intracellular platform involved in the activation of inflammatory processes). This upregulation exacerbates depressive symptomatology and further compounds gut dysbiosis. In this review we describe MDD/chronic stress-induced changes in: 1) NLRP3 inflammasome; 2) gut microbiota; and 3) metabolic pathways; and how inflammasome signaling may affect depressive-like behavior and gut microbiota composition. The implication is that novel therapeutic strategies could emerge for MDD and co-morbid conditions. A number of testable predictions surface from this microbiota-gut-inflammasome-brain hypothesis of MDD, using approaches that modulate gut microbiota composition via inflammasome modulation, fecal microbiota transplantation, psychobiotics supplementation, or dietary change.}, }
@article {pmid30003334, year = {2018}, author = {Adachi, K and Tamada, K}, title = {Microbial biomarkers for immune checkpoint blockade therapy against cancer.}, journal = {Journal of gastroenterology}, volume = {53}, number = {9}, pages = {999-1005}, pmid = {30003334}, issn = {1435-5922}, mesh = {Animals ; Antibodies, Monoclonal/therapeutic use ; Biomarkers, Tumor/*immunology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunologic Factors/therapeutic use ; Immunotherapy/*methods ; Mice ; Molecular Targeted Therapy/*methods ; Neoplasms/*immunology/*therapy ; Programmed Cell Death 1 Receptor/immunology ; Treatment Outcome ; }, abstract = {Three major standard treatments, i.e., surgery, chemotherapy, and radiotherapy, were traditionally applied to the treatment of cancer and saved many patients. Meanwhile, clinical studies as well as basic research of immunotherapy are being actively conducted for intractable or advanced malignancies that cannot be cured by the conventional standard treatments. Remarkable therapeutic efficacies have been recently reported in clinical trials on some cancer types, and immunotherapy is now being recognized as the "fourth" standard therapy against cancer. In particular, immune checkpoint inhibitor therapy (ICI) has demonstrated the effectiveness of immunotherapy through large-scale randomized clinical trials, leading to the paradigm-shift in cancer treatment. Immune checkpoint molecules transduce co-inhibitory signals to immunocompetent cells including T cells, and crucially contribute to the formation of an immunosuppressive microenvironment in tumor tissues, which intrinsically confers the treatment resistance. Programmed death-1 (PD-1, CD279) is one of the typical immune checkpoint molecules. Anti-tumor therapies targeting PD-1 and its ligands had been developed and approved in many countries, and various studies utilizing clinical specimens are currently progressing. In this review, we provide an overview of the biomarkers based on the analysis of enteric microbiota that correlate with the clinical efficacy/inefficacy of PD-1-based therapy.}, }
@article {pmid29997912, year = {2018}, author = {Heimesaat, MM and Escher, U and Grunau, A and Fiebiger, U and Bereswill, S}, title = {Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice - A Subacute Ileitis Model to Unravel Pathogen-Host Interactions.}, journal = {European journal of microbiology &amp; immunology}, volume = {8}, number = {2}, pages = {53-61}, pmid = {29997912}, issn = {2062-509X}, abstract = {Within 1 week following high-dose Toxoplasma gondii infection, mice develop lethal necrotizing ileitis. However, data from a subacute T. gondii-induced ileitis model are scarce. Therefore, mice harboring a human gut microbiota were perorally infected with one cyst of T. gondii. Within 9 days post-infection, the intestinal microbiota composition shifted towards higher loads of commensal enterobacteria and enterococci. Following T. gondii infection, mice were clinically only mildly affected, whereas ≈60% of mice displayed fecal blood and mild-to-moderate ileal histopathological changes. Intestinal inflammation was further characterized by increased apoptotic intestinal epithelial cells, which were accompanied by elevated proliferating gut epithelial cell numbers. As compared to naive controls, infected mice displayed elevated numbers of intestinal T lymphocytes and regulatory T-cells and increased pro-inflammatory mediator secretion. Remarkably, T. gondii-induced apoptotic and pro-inflammatory immune responses were not restricted to the gut, but could also be observed in extra-intestinal compartments including kidney, liver, and lung. Strikingly, low-dose T. gondii infection resulted in increased serum levels of pro- and anti-inflammatory cytokines. In conclusion, the here presented subacute ileitis model following peroral low-dose T. gondii infection of humanized mice allows for detailed investigations of the molecular mechanism underlying the "ménage à trois" of pathogens, human gut microbiota, and immunity.}, }
@article {pmid29997909, year = {2018}, author = {Escher, U and Giladi, E and Dunay, IR and Bereswill, S and Gozes, I and Heimesaat, MM}, title = {Anti-inflammatory Effects of the Octapeptide NAP in Human Microbiota-Associated Mice Suffering from Subacute Ileitis.}, journal = {European journal of microbiology &amp; immunology}, volume = {8}, number = {2}, pages = {34-40}, pmid = {29997909}, issn = {2062-509X}, abstract = {The octapeptide NAP is well known for its neuroprotective properties. We here investigated whether NAP treatment could alleviate pro-inflammatory immune responses during experimental subacute ileitis. To address this, mice with a human gut microbiota were perorally infected with one cyst of Toxoplasma gondii (day 0) and subjected to intraperitoneal synthetic NAP treatment from day 1 until day 8 postinfection (p.i.). Whereas placebo (PLC) control animals displayed subacute ileitis at day 9 p.i., NAP-treated mice exhibited less pronounced pro-inflammatory immune responses as indicated by lower numbers of intestinal mucosal T and B lymphocytes and lower interferon (IFN)-γ concentrations in mesenteric lymph nodes. The NAP-induced anti-inflammatory effects were not restricted to the intestinal tract but could also be observed in extra-intestinal including systemic compartments, given that pro-inflammatory cytokines were lower in liver, kidney, and lung following NAP as compared to PLC application, whereas at day 9 p.i., colonic and serum interleukin (IL)-10 concentrations were higher in the former as compared to the latter. Remarkably, probiotic commensal bifidobacterial loads were higher in the ileal lumen of NAP as compared to PLC-treated mice with ileitis. Our findings thus further support that NAP might be regarded as future treatment option directed against intestinal inflammation.}, }
@article {pmid29997755, year = {2018}, author = {Agholi, M and Safaei, A and Ramzi, M and Hatam, GR and Sarvari, J}, title = {A survey of the frequency of cytomegalovirus-associated diarrhea in immunocompromised patients using a non-invasive method.}, journal = {Iranian journal of microbiology}, volume = {10}, number = {2}, pages = {143-150}, pmid = {29997755}, issn = {2008-3289}, abstract = {BACKGROUND AND OBJECTIVES: Cytomegalovirus (CMV) infection is the most common viral opportunistic infection causing gastrointestinal diseases such diarrhea and colitis in immunocompromised patients. The development and performance of a robust and sensitive PCR assay are usually evaluated to detect CMV DNA in human fecal specimens. In this study, our aim was to detect CMV DNA in stool samples taken from patients with HIV/AIDS, cancer, and transplant recipient patients with chronic and persistent diarrhea using a non-invasive method.<br><br>MATERIALS AND METHODS: A total of 633 immunocompromised patients (451 males and 182 females) suffering from persistent or chronic diarrhea were included in this study. Among them, 392 were HIV/AIDS patients, 151 had cancer and were receiving chemotherapy, and 90 were recipients of a solid organ or bone marrow transplant. CMV genome was extracted from the stool samples using phenol: chloroform: isoamyl alcohol method. CMV DNA was identified by polymerase chain reaction using sequence specific primers on genomic DNA.<br><br>RESULTS: Looking at the frequency of CMV DNA in 392 HIV/AIDS patients, we found that only 5 patients (1.27%) were positive for CMV genome, while this frequency was 4.63% (7/151) and 5.5% (5/90) in patients with cancer receiving chemotherapy and in those with solid organ or bone marrow transplant, respectively.<br><br>CONCLUSION: The results of this study revealed that the cause of chronic or persistent diarrhea in HIV/AIDS, cancer, and graft recipient patients might be related to CMV infection. Accordingly, we recommend a non-invasive method, such as stool sample, as a first line of diagnosis of enteritis when the physician suspects that a patient has CMV infection.}, }
@article {pmid29992140, year = {2018}, author = {Bai, T and Zhang, L and Wang, H and Qian, W and Song, J and Hou, X}, title = {Fecal Microbiota Transplantation Is Effective in Relieving Visceral Hypersensitivity in a Postinfectious Model.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {3860743}, pmid = {29992140}, issn = {2314-6141}, mesh = {Animals ; *Bifidobacterium ; *Fecal Microbiota Transplantation ; Feces ; Male ; Mice ; Microbiota ; Trichinella spiralis ; }, abstract = {AIM: To investigate the effect of fecal microbiota transplantation on visceral hypersensitivity compared with Bifidobacterium longum.<br><br>METHODS: Mice visceral hypersensitivity was induced by Trichinella spiralis. After 8 weeks, they were divided into three groups (controls, Bifidobacterium longum, and fecal microbiota transplantation) and were daily treated by gavage with 0.2&#x2009;ml PBS, Bifidobacterium longum HB55020, or fecal microbiota for 7 days. Visceral hypersensitivity was tested with abdominal withdrawal reflex. Permeability of colon epithelium was assessed with Ussing chamber.<br><br>RESULTS: After administration of Bifidobacterium longum, compared with mice in postinfectious group, mice had higher pain threshold (p < 0.05). After administration of fecal microbiota, compared with mice in postinfectious group, mice had higher pain threshold (p < 0.05). Fecal microbiota transplantation was as effective as Bifidobacterium in relieving visceral hypersensitivity. Administration of Bifidobacterium longum or fecal microbiota transplantation improved colon epithelium permeability. Expression of occluding-1 was increased.<br><br>CONCLUSION: Manipulation of microbiota is effective in relieving visceral hypersensitivity. Fecal microbiota transplantation is as effective as Bifidobacterium longum administration.}, }
@article {pmid29991941, year = {2018}, author = {Moayyedi, P}, title = {Update on Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Disease.}, journal = {Gastroenterology &amp; hepatology}, volume = {14}, number = {5}, pages = {319-322}, pmid = {29991941}, issn = {1554-7914}, }
@article {pmid29983136, year = {2019}, author = {Cheng, CS and Wei, HK and Wang, P and Yu, HC and Zhang, XM and Jiang, SW and Peng, J}, title = {Early intervention with faecal microbiota transplantation: an effective means to improve growth performance and the intestinal development of suckling piglets.}, journal = {Animal : an international journal of animal bioscience}, volume = {13}, number = {3}, pages = {533-541}, doi = {10.1017/S1751731118001611}, pmid = {29983136}, issn = {1751-732X}, mesh = {Animals ; Fecal Microbiota Transplantation/*veterinary ; *Gastrointestinal Microbiome ; Intestines/immunology/*physiology ; Random Allocation ; Sus scrofa/growth &amp; development/immunology/*microbiology/*physiology ; }, abstract = {Recent studies indicate that early postnatal period is a critical window for gut microbiota manipulation to optimise the immunity and body growth. This study investigated the effects of maternal faecal microbiota orally administered to neonatal piglets after birth on growth performance, selected microbial populations, intestinal permeability and the development of intestinal mucosal immune system. In total, 12 litters of crossbred newborn piglets were selected in this study. Litter size was standardised to 10 piglets. On day 1, 10 piglets in each litter were randomly allotted to the faecal microbiota transplantation (FMT) and control groups. Piglets in the FMT group were orally administrated with 2ml faecal suspension of their nursing sow per day from the age of 1 to 3 days; piglets in the control group were treated with the same dose of a placebo (0.1M potassium phosphate buffer containing 10% glycerol (vol/vol)) inoculant. The experiment lasted 21 days. On days 7, 14 and 21, plasma and faecal samples were collected for the analysis of growth-related hormones and cytokines in plasma and lipocalin-2, secretory immunoglobulin A (sIgA), selected microbiota and short-chain fatty acids (SCFAs) in faeces. Faecal microbiota transplantation increased the average daily gain of piglets during week 3 and the whole experiment period. Compared with the control group, the FMT group had increased concentrations of plasma growth hormone and IGF-1 on days 14 and 21. Faecal microbiota transplantation also reduced the incidence of diarrhoea during weeks 1 and 3 and plasma concentrations of zonulin, endotoxin and diamine oxidase activities in piglets on days 7 and 14. The populations of Lactobacillus spp. and Faecalibacterium prausnitzii and the concentrations of faecal and plasma acetate, butyrate and total SCFAs in FMT group were higher than those in the control group on day 21. Moreover, the FMT piglets have higher concentrations of plasma transforming growth factor-β and immunoglobulin G, and faecal sIgA than the control piglets on day 21. These findings indicate that early intervention with maternal faecal microbiota improves growth performance, decreases intestinal permeability, stimulates sIgA secretion, and modulates gut microbiota composition and metabolism in suckling piglets.}, }
@article {pmid29981382, year = {2018}, author = {Imangaliyev, S and Prodan, A and Nieuwdorp, M and Groen, AK and van Riel, NAW and Levin, E}, title = {Domain intelligible models.}, journal = {Methods (San Diego, Calif.)}, volume = {149}, number = {}, pages = {69-73}, doi = {10.1016/j.ymeth.2018.06.011}, pmid = {29981382}, issn = {1095-9130}, mesh = {*Algorithms ; Gastrointestinal Microbiome/*physiology ; Humans ; Metagenome/*physiology ; *Models, Biological ; *Phylogeny ; }, abstract = {Mining biological information from rich "-omics" datasets is facilitated by organizing features into groups that are related to a biological phenomenon or clinical outcome. For example, microorganisms can be grouped based on a phylogenetic tree that depicts their similarities regarding genetic or physical characteristics. Here, we describe algorithms that incorporate auxiliary information in terms of groups of predictors and the relationships between them into the metagenome learning task to build intelligible models. In particular, our cost function guides the feature selection process using auxiliary information by requiring related groups of predictors to provide similar contributions to the final response. We apply the developed algorithms to a recently published dataset analyzing the effects of fecal microbiota transplantation (FMT) in order to identify factors that are associated with improved peripheral insulin sensitivity, leading to accurate predictions of the response to the FMT.}, }
@article {pmid29980607, year = {2018}, author = {Halkjær, SI and Christensen, AH and Lo, BZS and Browne, PD and Günther, S and Hansen, LH and Petersen, AM}, title = {Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study.}, journal = {Gut}, volume = {67}, number = {12}, pages = {2107-2115}, doi = {10.1136/gutjnl-2018-316434}, pmid = {29980607}, issn = {1468-3288}, mesh = {Adolescent ; Adult ; Double-Blind Method ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Male ; Middle Aged ; Psychometrics ; Quality of Life ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: IBS is associated with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clinical outcome in patients with IBS.<br><br>DESIGN: We performed this study in 52 adult patients with moderate-to-severe IBS. At the screening visit, clinical history and symptoms were assessed and faecal samples were collected. Patients were randomised to FMT or placebo capsules for 12 days and followed for 6 months. Study visits were performed at baseline, 1, 3 and 6 months, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected.<br><br>RESULTS: A significant difference in improvement in IBS-SSS score was observed 3 months after treatment (p=0.012) favouring placebo. This was similar for IBS-QoL data after 3 months (p=0.003) favouring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not.<br><br>CONCLUSION: In this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months. Altering the gut microbiota is not enough to obtain clinical improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS.<br><br>TRIAL REGISTRATION NUMBER: NCT02788071.}, }
@article {pmid29976114, year = {2018}, author = {Wang, J and Wang, P and Tian, H and Tian, F and Zhang, Y and Zhang, L and Gao, X and Wang, X}, title = {Aryl hydrocarbon receptor/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota in mice.}, journal = {Innate immunity}, volume = {24}, number = {5}, pages = {297-306}, pmid = {29976114}, issn = {1753-4267}, mesh = {Animals ; Anti-Bacterial Agents ; Basic Helix-Loop-Helix Transcription Factors/antagonists &amp; inhibitors/*metabolism ; Carbazoles/administration &amp; dosage/pharmacology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Interleukins/*metabolism ; Intestinal Mucosa/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Pancreatitis-Associated Proteins/metabolism ; Protein Precursors/metabolism ; Receptors, Aryl Hydrocarbon/antagonists &amp; inhibitors/*metabolism ; STAT3 Transcription Factor/*metabolism ; Signal Transduction ; Interleukin-22 ; }, abstract = {Compelling evidence demonstrates the crucial role of the commensal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. However, the effects of commensal microbiota on intestinal mucosa antimicrobial molecules have not been elucidated systematically. Here, we investigate the impacts of antibiotic-induced depletion and subsequent restoration of the intestinal microbiota on the murine antimicrobial molecules in intestinal mucosa. Our results demonstrate that depletion of commensal microbiota leads to intestinal mucosa atrophy and reduction of antimicrobial molecules, including lysozyme, regenerating islet-derived protein 3 gamma (RegIIIγ), and cryptdin 5 mRNA, whereas subsequent reconstitution of intestinal microbiota by fecal microbiota transplantation (FMT) rescues mucosa morphology and antimicrobials. Importantly, our study shows that down-regulation of aryl hydrocarbon receptor (AhR), interleukin-22 (IL-22), and phosphorylated Stat3 (p-Stat3) is associated with decreased antimicrobials, which might mediate the antibiotic-associated intestinal mucosa injury. Last, exogenous activation of the AhR/IL-22/Stat3 signaling pathway with the AhR agonist 6-formylindolo(3,2-b)carbazole (Ficz) rescued antimicrobial molecule levels markedly after antibiotic treatment to levels similar to those following reconstitution of intestinal microbiota by FMT. Together, our results demonstrate that the AhR/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota and suggest this pathway as a promising target in the treatment of antibiotic-associated gut barrier damage.}, }
@article {pmid29974940, year = {2018}, author = {Esposito, L and Veraldi, S}, title = {Skin bacterial colonizations and superinfections in immunocompetent patients with scabies.}, journal = {International journal of dermatology}, volume = {57}, number = {10}, pages = {1218-1220}, doi = {10.1111/ijd.14123}, pmid = {29974940}, issn = {1365-4632}, mesh = {Adult ; Escherichia coli Infections/*diagnosis ; Female ; Humans ; Immunocompetence ; Male ; Middle Aged ; Scabies/*complications ; Skin/microbiology ; Staphylococcal Skin Infections/*diagnosis ; Superinfection/*microbiology ; Young Adult ; }, abstract = {BACKGROUND: Skin bacterial colonizations and superinfections are well-known complications of scabies, in particular, in tropical and subtropical countries. However, only very rare studies on skin bacterial colonizations and superinfections have been carried out in immunocompetent patients with scabies living in Western countries.<br><br>METHODS: Eighty-nine Caucasian adult immunocompetent patients with scabies living in Milan, Italy, were subjected to bacteriologic examinations of the skin. Clinical diagnosis of scabies was confirmed in all patients by means of microscopic examinations: they were considered positive when adults or eggs or feces of Sarcoptes scabiei var. hominis were visible. In all patients, six skin swabs (three for aerobic and three for anaerobic bacteria) were taken in three different areas before the beginning of the treatment.<br><br>RESULTS: No clinical manifestations of pyoderma were observed. Bacteriologic examinations were positive in 5/89 patients (5.6%). Bacteriologic cultures were positive for Staphylococcus aureus in all five patients; in one patient, they were also positive for Escherichia coli. No growth of anaerobic bacteria was recorded.<br><br>CONCLUSIONS: According to the results of this study, skin bacterial colonizations and superinfections in immunocompetent adult patients with scabies living in Milan are uncommon. Bacteriologic examinations may therefore be considered as an unnecessary routine procedure.}, }
@article {pmid29973630, year = {2018}, author = {Hart, ML and Ericsson, AC and Lloyd, KCK and Grimsrud, KN and Rogala, AR and Godfrey, VL and Nielsen, JN and Franklin, CL}, title = {Development of outbred CD1 mouse colonies with distinct standardized gut microbiota profiles for use in complex microbiota targeted studies.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {10107}, pmid = {29973630}, issn = {2045-2322}, support = {P40 OD010995/OD/NIH HHS/United States ; T32 OD0112639//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/International ; U42 OD010924/OD/NIH HHS/United States ; T32 OD011126/OD/NIH HHS/United States ; K01 OD019924/OD/NIH HHS/United States ; U42 OD012210/OD/NIH HHS/United States ; U42 OD010918/OD/NIH HHS/United States ; U2C DK092993/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Breeding/*methods ; Embryo Transfer/methods ; Fecal Microbiota Transplantation/*methods ; Female ; *Gastrointestinal Microbiome ; Housing, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Models, Animal ; }, abstract = {Studies indicate that the gut microbiota (GM) can significantly influence both local and systemic host physiologic processes. With rising concern for optimization of experimental reproducibility and translatability, it is essential to consider the GM in study design. However, GM profiles can vary between rodent producers making consistency between models challenging. To circumvent this, we developed outbred CD1 mouse colonies with stable, complex GM profiles that can be used as donors for a variety of GM transfer techniques including rederivation, co-housing, cross-foster, and fecal microbiota transfer (FMT). CD1 embryos were surgically transferred into CD1 or C57BL/6 surrogate dams that varied by GM composition and complexity to establish four separate mouse colonies harboring GM profiles representative of contemporary mouse producers. Using targeted 16S rRNA amplicon sequencing, subsequent female offspring were found to have similar GM profiles to surrogate dams. Furthermore, breeding colonies of CD1 mice with distinct GM profiles were maintained for nine generations, demonstrating GM stability within these colonies. To confirm GM stability, we shipped cohorts of these four colonies to collaborating institutions and found no significant variation in GM composition. These mice are an invaluable experimental resource that can be used to investigate GM effects on mouse model phenotype.}, }
@article {pmid29972839, year = {2018}, author = {Klag, T and Wehkamp, J}, title = {[Crohn's Disease - New Therapies].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {113}, number = {13}, pages = {953-959}, doi = {10.1055/a-0538-3671}, pmid = {29972839}, issn = {1439-4413}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use ; Clinical Trials as Topic ; Colitis, Ulcerative/immunology/*therapy ; Crohn Disease/immunology/*therapy ; Defensins/adverse effects/therapeutic use ; Fecal Microbiota Transplantation ; Humans ; Immunosuppressive Agents/adverse effects/therapeutic use ; Integrins/antagonists &amp; inhibitors ; Lecithins/therapeutic use ; Probiotics/adverse effects/therapeutic use ; Ustekinumab/therapeutic use ; }, abstract = {New promising treatment options for chronic inflammatory bowel diseases, confirm the expanded pathophysiological understanding in terms of the interactions of the gastrointestinal microbiome with the adaptive and innate immune response and barrier protection. Therefore, these interrelations are focus of research and therapeutic strategies. The following review will give insights into the pathomechanisms, current treatment options and future developments.}, }
@article {pmid29971061, year = {2018}, author = {Hu, J and Chen, L and Tang, Y and Xie, C and Xu, B and Shi, M and Zheng, W and Zhou, S and Wang, X and Liu, L and Yan, Y and Yang, T and Niu, Y and Hou, Q and Xu, X and Yan, X}, title = {Standardized Preparation for Fecal Microbiota Transplantation in Pigs.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1328}, pmid = {29971061}, issn = {1664-302X}, abstract = {The intestine of pigs harbors a mass of microorganisms which are essential for intestinal homeostasis and host health. Intestinal microbial disorders induce enteric inflammation and metabolic dysfunction, thereby causing adverse effects on the growth and health of pigs. In the human medicine, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, has shown efficacy in intestinal microbiota restoration. In addition, it has been used widely in therapy for human gastrointestinal diseases, including Clostridium difficile infection, inflammatory bowel diseases, and irritable bowel syndrome. Given that pigs share many similarities with humans, in terms of anatomy, nutritional physiology, and intestinal microbial compositions, FMT may also be used to restore the normal intestinal microbiota of pigs. However, feasible procedures for performing FMT in pigs remains unclear. Here, we summarize a standardized preparation for FMT in pigs by combining the standard methodology for human FMT with pig production. The key issues include the donor selection, fecal material preparation, fecal material transfer, stool bank establishment, and the safety for porcine FMT. Optimal donors should be selected to ensure the efficacy of porcine FMT and reduce the risks of transmitting infectious diseases to recipients during FMT. Preparing for fresh fecal material is highly recommended. Alternatively, frozen fecal suspension can also be prepared as an optimal choice because it is convenient and has similar efficacy. Oral administration of fecal suspension could be an optimal method for porcine fecal material transfer. Furthermore, the dilution ratio of fecal materials and the frequency of fecal material transfer could be adjusted according to practical situations in the pig industry. To meet the potential large-scale requirement in the pig industry, it is important to establish a stool bank to make porcine FMT readily available. Future studies should also focus on providing more robust safety data on FMT to improve the safety and tolerability of the recipient pigs. This standardized preparation for porcine FMT can facilitate the development of microbial targeted therapies and improve the intestinal health of pigs.}, }
@article {pmid29966323, year = {2018}, author = {Chai, J and Lee, CH}, title = {Management of Primary and Recurrent Clostridium difficile Infection: An Update.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {7}, number = {3}, pages = {}, pmid = {29966323}, issn = {2079-6382}, abstract = {Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections (HAI) in the United States and Canada, and incidence rates have increased worldwide in recent decades. Currently, antibiotics are the mainstay treatments for both primary and recurrent CDI, but their efficacy is limited, prompting further therapies to be developed. Aim: This review summarizes current and emerging therapies in CDI management including antibiotics, fecal microbiota transplantation, monoclonal antibodies, spore-based therapies, and vaccinations.}, }
@article {pmid29954618, year = {2019}, author = {Vázquez-Zapién, GJ and Ordoñez-Gutiérrez, ME and Minero-Alfaro, JI and Guerrero-Guerrero, VH and Mora-Mendoza, I and Mata-Miranda, MM}, title = {Functional and histologic effects after implanting pluripotent stem cells in a murine model with sphincterotomy.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {84}, number = {2}, pages = {165-173}, doi = {10.1016/j.rgmx.2018.03.009}, pmid = {29954618}, issn = {2255-534X}, mesh = {Anal Canal/physiopathology/*surgery ; Animals ; Fecal Incontinence/etiology/physiopathology/*therapy ; Female ; Manometry ; Pluripotent Stem Cells/*transplantation ; Postoperative Complications/*therapy ; Rats ; Rats, Wistar ; Regeneration ; Sphincterotomy/*adverse effects ; Treatment Outcome ; }, abstract = {INTRODUCTION AND AIMS: Fecal incontinence is a disabling condition with devastating consequences for the patients. Medical and surgical options are not very satisfactory, reason by which regenerative medicine has been considered in this field. In the present research, we analyzed functional and histologic effects after implanting pluripotent stem cells (PSCs) in a murine model with sphincterotomy.<br><br>MATERIALS AND METHODS: Female Wistar rats were subjected to sphincterotomy and divided into three groups. Group 1 (control group) was treated with 300&#x3bc;L of balanced saline solution and group 2 (late treatment) and group 3 (early treatment) received 50,000 PSCs resuspended in 300&#x3bc;L of balanced saline solution. All animals were evaluated through high-resolution anorectal manometry 24hours before and after sphincterotomy and every month for three months. Finally, the rats were euthanized and histopathologic sections from the anal canal were obtained.<br><br>RESULTS: All groups showed a decrease in resting anal pressure and squeeze anal pressure 24hours after sphincterotomy. At the third month, higher anal pressures in the groups treated with PSCs were detected. Regarding the histologic effects, the microscopic architecture was restored and there was a significant decrease in the inflammatory response in the groups treated with PSCs.<br><br>CONCLUSION: PSCs implantation improves anal tone, as well as histologic structure, presenting better regenerative results when implanted as early treatment.}, }
@article {pmid29953876, year = {2018}, author = {van der Beek, CM and Canfora, EE and Kip, AM and Gorissen, SHM and Olde Damink, SWM and van Eijk, HM and Holst, JJ and Blaak, EE and Dejong, CHC and Lenaerts, K}, title = {The prebiotic inulin improves substrate metabolism and promotes short-chain fatty acid production in overweight to obese men.}, journal = {Metabolism: clinical and experimental}, volume = {87}, number = {}, pages = {25-35}, doi = {10.1016/j.metabol.2018.06.009}, pmid = {29953876}, issn = {1532-8600}, mesh = {Adult ; Appetite/drug effects ; Blood Glucose/analysis ; Cross-Over Studies ; Dietary Carbohydrates/metabolism ; Double-Blind Method ; Energy Metabolism/drug effects ; Fatty Acids, Volatile/*biosynthesis ; Feces/chemistry ; Humans ; Insulin/blood ; Inulin/pharmacology/*therapeutic use ; Lipids/blood ; Male ; Middle Aged ; Obesity/*drug therapy/*metabolism ; Overweight/*drug therapy/*metabolism ; Oxidation-Reduction ; *Prebiotics ; Satiety Response/drug effects ; Young Adult ; }, abstract = {BACKGROUND AND AIMS: Human gut microbiota play an important role in maintaining human health. Dietary fibers, i.e. prebiotics, are fermented by human gut microbiota into the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. SCFAs promote fat oxidation and improve metabolic health. Therefore, the prebiotic inulin might be an effective dietary strategy to improve human metabolism. We aimed to investigate the acute metabolic effects of ingesting inulin compared with digestible carbohydrates and to trace inulin-derived SCFAs using stable isotope tracer methodology.<br><br>METHODS: In a double-blind, randomized, placebo-controlled crossover design, 14 healthy, overweight to obese men consumed a high-fat milkshake containing A) 24&#x202f;g inulin of which 0.5&#x202f;g was U-[13]C-inulin (INU) or B) 24&#x202f;g maltodextrin placebo (PLA), with a wash-out period of at least five days. Fat oxidation was measured via an open-circuit ventilated hood and blood samples were collected up to 7&#x202f;h after ingestion. Plasma, breath, and fecal samples were collected, and appetite and satiety scores were assessed.<br><br>RESULTS: Fat oxidation increased in the early postprandial phase (0-3&#x202f;h), and both plasma glucose and insulin were lower after INU ingestion compared with PLA (all P&#x202f;<&#x202f;0.05). Plasma free fatty acids were higher in the early, and lower in the late postprandial period after INU ingestion. Inulin was fermented into SCFAs as indicated by higher plasma acetate concentrations after INU compared with PLA (P&#x202f;<&#x202f;0.05). In addition, we found continuous increases in plasma [13]C-SCFA enrichments (P&#x202f;<&#x202f;0.05 from t&#x202f;=&#x202f;120 onwards) and breath [13]CO2 enrichments after INU intake. There were no effects on plasma triglycerides, free glycerol, satiety hormones GLP-1 and PYY, and appetite and satiety scores.<br><br>CONCLUSIONS: Ingestion of the prebiotic inulin improves fat oxidation and promotes SCFA production in overweight to obese men. Overall, replacing digestible carbohydrates with the fermentable inulin may favor human substrate metabolism.<br><br>CLINICAL TRIAL REGISTRY: The trial was registered at clinicaltrials.gov under number NCT02009670.}, }
@article {pmid29946308, year = {2018}, author = {Baktash, A and Terveer, EM and Zwittink, RD and Hornung, BVH and Corver, J and Kuijper, EJ and Smits, WK}, title = {Mechanistic Insights in the Success of Fecal Microbiota Transplants for the Treatment of Clostridium difficile Infections.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1242}, pmid = {29946308}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation has proven to be an effective treatment for infections with the gram-positive enteropathogen Clostridium difficile. Despite its effectiveness, the exact mechanisms that underlie its success are largely unclear. In this review, we highlight the pleiotropic effectors that are transferred during fecal microbiota transfer and relate this to the C. difficile lifecycle. In doing so, we show that it is likely that multiple factors contribute to the elimination of symptoms of C. difficile infections after fecal microbiota transplantation.}, }
@article {pmid29943234, year = {2018}, author = {Bellocchi, C and Volkmann, ER}, title = {Update on the Gastrointestinal Microbiome in Systemic Sclerosis.}, journal = {Current rheumatology reports}, volume = {20}, number = {8}, pages = {49}, pmid = {29943234}, issn = {1534-6307}, mesh = {Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Inflammation/microbiology ; Scleroderma, Systemic/*microbiology ; }, abstract = {PURPOSE OF REVIEW: Accumulating evidence suggests that gut microbiota affect the development and function of the immune system and may play a role in the pathogenesis of autoimmune diseases. The purpose of this review is to summarize recent studies reporting gastrointestinal microbiota aberrations associated with the systemic sclerosis disease state.<br><br>RECENT FINDINGS: The studies described herein have identified common changes in gut microbial composition. Specifically, patients with SSc have decreased abundance of beneficial commensal genera (e.g., Faecalibacterium, Clostridium, and Bacteroides) and increased abundance of pathobiont genera (e.g., Fusobacterium, Prevotella, Erwinia). In addition, some studies have linked specific genera with the severity of gastrointestinal symptoms in systemic sclerosis. More research is needed to further characterize the gastrointestinal microbiota in systemic sclerosis and understand how microbiota perturbations can affect inflammation, fibrosis, and clinical outcomes. Interventional studies aimed at addressing/correcting these perturbations, either through dietary modification, pro/pre-biotic supplementation, or fecal transplantation, may lead to improved outcomes for patients with systemic sclerosis.}, }
@article {pmid29942096, year = {2018}, author = {Hoyles, L and Fernández-Real, JM and Federici, M and Serino, M and Abbott, J and Charpentier, J and Heymes, C and Luque, JL and Anthony, E and Barton, RH and Chilloux, J and Myridakis, A and Martinez-Gili, L and Moreno-Navarrete, JM and Benhamed, F and Azalbert, V and Blasco-Baque, V and Puig, J and Xifra, G and Ricart, W and Tomlinson, C and Woodbridge, M and Cardellini, M and Davato, F and Cardolini, I and Porzio, O and Gentileschi, P and Lopez, F and Foufelle, F and Butcher, SA and Holmes, E and Nicholson, JK and Postic, C and Burcelin, R and Dumas, ME}, title = {Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women.}, journal = {Nature medicine}, volume = {24}, number = {7}, pages = {1070-1080}, pmid = {29942096}, issn = {1546-170X}, support = {MR/L01632X/1/MRC_/Medical Research Council/United Kingdom ; MR/M501797/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Cells, Cultured ; Cohort Studies ; Confounding Factors, Epidemiologic ; Diabetes Mellitus/*genetics ; Fecal Microbiota Transplantation ; Female ; Hepatocytes/metabolism ; Humans ; Metabolome ; Metabolomics ; *Metagenomics ; Mice ; Microbiota ; Non-alcoholic Fatty Liver Disease/*genetics ; Obesity/*genetics ; Phenotype ; Transcriptome/genetics ; }, abstract = {Hepatic steatosis is a multifactorial condition that is often observed in obese patients and is a prelude to non-alcoholic fatty liver disease. Here, we combine shotgun sequencing of fecal metagenomes with molecular phenomics (hepatic transcriptome and plasma and urine metabolomes) in two well-characterized cohorts of morbidly obese women recruited to the FLORINASH study. We reveal molecular networks linking the gut microbiome and the host phenome to hepatic steatosis. Patients with steatosis have low microbial gene richness and increased genetic potential for the processing of dietary lipids and endotoxin biosynthesis (notably from Proteobacteria), hepatic inflammation and dysregulation of aromatic and branched-chain amino acid metabolism. We demonstrated that fecal microbiota transplants and chronic treatment with phenylacetic acid, a microbial product of aromatic amino acid metabolism, successfully trigger steatosis and branched-chain amino acid metabolism. Molecular phenomic signatures were predictive (area under the curve = 87%) and consistent with the gut microbiome having an effect on the steatosis phenome (>75% shared variation) and, therefore, actionable via microbiome-based therapies.}, }
@article {pmid29941542, year = {2018}, author = {Zhao, M and Xiong, X and Ren, K and Xu, B and Cheng, M and Sahu, C and Wu, K and Nie, Y and Huang, Z and Blumberg, RS and Han, X and Ruan, HB}, title = {Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut inflammation.}, journal = {EMBO molecular medicine}, volume = {10}, number = {8}, pages = {}, pmid = {29941542}, issn = {1757-4684}, support = {P30 DK078392/DK/NIDDK NIH HHS/United States ; R01 DK088199/DK/NIDDK NIH HHS/United States ; R21 AI103388/AI/NIAID NIH HHS/United States ; }, mesh = {Acetylglucosamine/*metabolism ; Animals ; Colitis/pathology/therapy ; Dysbiosis/physiopathology ; Epithelial Cells/*metabolism ; Fecal Microbiota Transplantation ; Female ; Homeostasis ; Humans ; Inflammatory Bowel Diseases/*metabolism/therapy ; Intestinal Mucosa/*metabolism/physiopathology ; Male ; Mice ; N-Acetylglucosaminyltransferases/*metabolism ; Paneth Cells/metabolism/pathology ; Protein Processing, Post-Translational/physiology ; Pyrans/pharmacology/therapeutic use ; STAT Transcription Factors/metabolism ; Thiazoles/pharmacology/therapeutic use ; beta-N-Acetylhexosaminidases/antagonists &amp; inhibitors/*metabolism ; }, abstract = {Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored. Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients. Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice. Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical-induced colitis. Paneth cell-specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical-induced colitis. On the other hand, the augmentation of O-GlcNAc signaling by inhibiting O-GlcNAcase, the enzyme removing O-GlcNAcylation, alleviated chemical-induced colitis. Our data reveal that protein O-GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.}, }
@article {pmid29939968, year = {2018}, author = {Bouri, S and Hart, A}, title = {Fecal microbial transplantation: an update.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {21}, number = {5}, pages = {405-410}, doi = {10.1097/MCO.0000000000000488}, pmid = {29939968}, issn = {1473-6519}, mesh = {Clostridium Infections/therapy ; Colitis, Ulcerative/microbiology/therapy ; Donor Selection ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation/adverse effects/methods/trends ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/therapy ; }, abstract = {PURPOSE OF REVIEW: The purpose of this article is to provide an update on recent developments in fecal microbiota transplantation (FMT) in the last year.<br><br>RECENT FINDINGS: Although FMT is an accepted treatment for recurrent Clostridium difficile infection (CDI), recently it is also gaining acceptance for the treatment of refractory CDI. FMT is showing promise in ulcerative colitis and is experimental in many other conditions. The optimal practical aspects to enhance the success of FMT are still being established.<br><br>SUMMARY: The implication of current research is that the indications of FMT may be extended to other conditions in the future.}, }
@article {pmid29939391, year = {2018}, author = {Korzeniewski, K and Osińska, J and Korsak, J and Konior, M}, title = {Hepatitis E virus seroprevalence in Polish soldiers serving in harsh environmental conditions.}, journal = {International maritime health}, volume = {69}, number = {2}, pages = {137-141}, doi = {10.5603/IMH.2018.0020}, pmid = {29939391}, issn = {2081-3252}, mesh = {Adult ; Africa ; Asia ; Female ; Hepatitis Antibodies/blood ; Hepatitis E/*epidemiology ; Hepatitis E virus/*immunology ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Male ; Middle Aged ; Military Personnel/*statistics &amp; numerical data ; Poland/epidemiology ; Seroepidemiologic Studies ; }, abstract = {BACKGROUND: Hepatitis E virus (HEV) is an under-recognised aetiological factor of viral hepatitis; it is most commonly transmitted via the oral-faecal route, but can also be transmitted by blood or blood products, vertically from an infected mother to the foetus or by transplanted organs. The aim of the study was to present the current seroprevalence of HEV among soldiers from the Polish Special Forces deployed on military operations carried out in harsh environmental conditions.<br><br>MATERIALS AND METHODS: The research conducted between October and November 2016 involved 253 active duty soldiers, 237 men and 16 women, aged 26-57, without clinical symptoms of infection, participants in military operations in Asia and Africa. Accurate HEV diagnosis required the implementation of a two-phase diagnostic protocol. During the first phase, immunoenzymatic ELISA method was used to detect specific anti-HEV antibodies (IgM and IgG) in blood serum samples indicating contact with an infectious agent in the past. During the second phase, serum samples obtained from subjects with positive or inconclusive test results were tested again using confirmatory recomLine HEV IgM/IgG immunoassay.<br><br>RESULTS: Immunoenzymatic assay found anti-HEV antibodies (IgM and/or IgG) in blood serum samples obtained from 18 soldiers. Confirmatory tests were carried out among soldiers tested positive with ELISA or those with inconclusive test results; the confirmatory tests showed anti-HEV antibodies (IgM and/or IgG) in 16 of the studied soldiers, i.e. 6.3% of the study group.<br><br>CONCLUSIONS: The occurrence of HEV infections in Polish soldiers justifies the need for the introduction of screening tests for HEV in the military environment, especially among blood donors and in cases of whole blood or blood products transfusion.}, }
@article {pmid29934134, year = {2018}, author = {Zaheer, M and Wang, C and Bian, F and Yu, Z and Hernandez, H and de Souza, RG and Simmons, KT and Schady, D and Swennes, AG and Pflugfelder, SC and Britton, RA and de Paiva, CS}, title = {Protective role of commensal bacteria in Sjögren Syndrome.}, journal = {Journal of autoimmunity}, volume = {93}, number = {}, pages = {45-56}, pmid = {29934134}, issn = {1095-9157}, support = {P30 CA125123/CA/NCI NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; T32 AI053831/AI/NIAID NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; R01 EY026893/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology/pathology ; Cornea/*immunology/pathology ; Dacryocystitis/genetics/immunology/*microbiology/pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/immunology ; Gene Expression Regulation ; Germ-Free Life ; Goblet Cells/immunology/pathology ; Homeodomain Proteins/genetics/*immunology ; Interferon-gamma/genetics/immunology ; Interleukin-12/genetics/immunology ; Interleukin-2 Receptor alpha Subunit/deficiency/genetics/*immunology ; Lacrimal Apparatus/*immunology/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Permeability ; Sjogren's Syndrome/genetics/immunology/*microbiology/pathology ; Symbiosis/*immunology ; }, abstract = {CD25 knock-out (CD25KO) mice spontaneously develop Sjögren Syndrome (SS)-like inflammation. We investigated the role of commensal bacteria by comparing CD25KO mice housed in conventional or germ-free conditions. Germ-free CD25KO mice have greater corneal barrier dysfunction, lower goblet cell density, increased total lymphocytic infiltration score, increased expression of IFN-γ, IL-12 and higher a frequency of CD4[+]IFN-γ[+] cells than conventional mice. CD4[+] T cells isolated from female germ-free CD25KO mice adoptively transferred to naive immunodeficient RAG1KO recipients caused more severe Sjögren-like disease than CD4[+] T cells transferred from conventional CD25KO mice. Fecal transplant in germ-free CD25KO mice reversed the spontaneous dry eye phenotype and decreased the generation of pathogenic CD4[+]IFN-γ[+] cells. Our studies indicate that lack of commensal bacteria accelerates the onset and severity of dacryoadenitis and generates autoreactive CD4[+]T cells with greater pathogenicity in the CD25KO model, suggesting that the commensal bacteria or their metabolites products have immunoregulatory properties that protect exocrine glands in the CD25KO SS model.}, }
@article {pmid29933742, year = {2018}, author = {Cui, B and Su, D and Li, W and She, X and Zhang, M and Wang, R and Zhai, Q}, title = {Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer's disease.}, journal = {Journal of neuroinflammation}, volume = {15}, number = {1}, pages = {190}, pmid = {29933742}, issn = {1742-2094}, mesh = {Aging/blood/*genetics ; Animals ; Avoidance Learning/physiology ; Brain/*metabolism ; Claudins/genetics/metabolism ; Cognition Disorders/etiology ; Corticosterone/blood ; Cytokines/genetics/*metabolism ; Disease Models, Animal ; Endotoxins/blood ; Gastrointestinal Microbiome/*physiology ; Inflammation/etiology/metabolism ; Mice ; Microbiota/physiology ; Noise/*adverse effects ; Occludin/genetics/metabolism ; RNA, Ribosomal, 16S/metabolism ; Serotonin/blood ; Tight Junctions/pathology ; Zonula Occludens-1 Protein/genetics/metabolism ; Zonula Occludens-2 Protein/genetics/metabolism ; gamma-Aminobutyric Acid/blood ; }, abstract = {BACKGROUND: Chronic noise exposure is associated with neuroinflammation and gut microbiota dysregulation and increases the risk of Alzheimer's disease (AD). Environmental hazards are also thought to be associated with genetic susceptibility factors that increase AD pathogenesis. However, there is limited experimental evidence regarding the link between chronic noise stress and microbiome-gut-brain axis alterations, which may be closely related to AD development.<br><br>METHODS: The aim of the present study was to systematically investigate the effects of chronic noise exposure on the microbiome-gut-brain axis in the senescence-accelerated mouse prone 8 (SAMP8) strain. We established SAMP8 mouse models to examine the consequences of noise exposure on the microbiome-gut-brain axis. Hippocampal amyloid-&#x3b2; (A&#x3b2;) assessment and the Morris water maze were used to evaluate AD-like changes, 16S ribosomal RNA sequencing analyses were used for intestinal flora measurements, and assessment of endothelial tight junctions and serum neurotransmitter and inflammatory mediator levels, as well as fecal microbiota transplant, was conducted to explore the underlying pathological mechanisms.<br><br>RESULTS: Chronic noise exposure led to cognitive impairment and A&#x3b2; accumulation in young SAMP8 mice, similar to that observed in aging SAMP8 mice. Noise exposure was also associated with decreased gut microbiota diversity and compositional alterations. Axis-series studies showed that endothelial tight junction proteins were decreased in both the intestine and brain, whereas serum neurotransmitter and inflammatory mediator levels were elevated in young SAMP8 mice exposed to chronic noise, similar to the observations made in the aging group. The importance of intestinal bacteria in noise exposure-induced epithelial integrity impairment and A&#x3b2; accumulation was further confirmed through microbiota transplantation experiments. Moreover, the effects of chronic noise were generally intensity-dependent.<br><br>CONCLUSION: Chronic noise exposure altered the gut microbiota, accelerated age-related neurochemical and inflammatory dysregulation, and facilitated AD-like changes in the brain of SAMP8 mice.}, }
@article {pmid29933546, year = {2018}, author = {Desselberger, U}, title = {The Mammalian Intestinal Microbiome: Composition, Interaction with the Immune System, Significance for Vaccine Efficacy, and Potential for Disease Therapy.}, journal = {Pathogens (Basel, Switzerland)}, volume = {7}, number = {3}, pages = {}, pmid = {29933546}, issn = {2076-0817}, abstract = {The mammalian gut is colonized by a large variety of microbes, collectively termed ‘the microbiome’. The gut microbiome undergoes rapid changes during the first few years of life and is highly variable in adulthood depending on various factors. With the gut being the largest organ of immune responses, the composition of the microbiome of the gut has been found to be correlated with qualitative and quantitative differences of mucosal and systemic immune responses. Animal models have been very useful to unravel the relationship between gut microbiome and immune responses and for the understanding of variations of immune responses to vaccination in different childhood populations. However, the molecular mechanisms underlying optimal immune responses to infection or vaccination are not fully understood. The gut virome and gut bacteria can interact, with bacteria facilitating viral infectivity by different mechanisms. Some gut bacteria, which have a beneficial effect on increasing immune responses or by overgrowing intestinal pathogens, are considered to act as probiotics and can be used for therapeutic purposes (as in the case of fecal microbiome transplantation).}, }
@article {pmid29931479, year = {2018}, author = {Philips, CA and Phadke, N and Ganesan, K and Ranade, S and Augustine, P}, title = {Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {37}, number = {3}, pages = {215-225}, pmid = {29931479}, issn = {0975-0711}, mesh = {Administration, Oral ; Adult ; Aged ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Hepatitis, Alcoholic/microbiology/*therapy ; Humans ; Male ; Middle Aged ; *Nutrition Therapy ; Pentoxifylline/*therapeutic use ; Prednisolone/*administration &amp; dosage ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {INTRODUCTION: Alcohol-induced intestinal dysbiosis is central to the development of the severe alcoholic liver disease. We present the first study to compare outcomes in patients of severe alcoholic hepatitis (SAH) on nutritional therapy, corticosteroids, pentoxifylline, and healthy donor fecal transplantation (FMT) and discuss distinct microbial community and microbiome metabolic functional changes after FMT.<br><br>METHODS: Out of 1271 liver disease patients, 809 (63.7%) were diagnosed to have the alcoholic liver disease, of which 51 patients (8 treated with corticosteroids, 17 with nutritional support only, 10 with pentoxifylline, 16 receiving FMT) were included. Clinical, biochemical parameters, liver disease, and alcoholic hepatitis severity scores at baseline and mortality at the end of 1 and 3&#xa0;months were analyzed between groups. Stool microbiota (SM) analysis was performed for healthy controls (HC) and respective recipients after FMT.<br><br>RESULTS: All the patients were male. The proportions of patients surviving at the end of 1 and 3&#xa0;months in the steroids, nutrition, pentoxifylline, and FMT group were 63%, 47%, 40% and 75% [p&#x2009;=&#x2009;0.179] and 38%, 29%, 30%, and 75% [p&#x2009;=&#x2009;0.036], respectively. When compared with FMT, relative risk and hazard ratios for death were higher in all the other groups. Following FMT, distinct and beneficial modulation of SM and pathways of dysregulated metabolism, infections, inflammation, and oxidative stress in SAH patients were noted in tandem with improved clinical outcomes.<br><br>CONCLUSIONS: Healthy donor FMT for SAH improves survival beyond what is offered by current therapies and can function as a cost-effective bridge to liver transplant (LT) or for improving transplant-free survival. Larger studies and randomized trials are unmet needs.}, }
@article {pmid29929472, year = {2018}, author = {Kumar, A and Vlasova, AN and Deblais, L and Huang, HC and Wijeratne, A and Kandasamy, S and Fischer, DD and Langel, SN and Paim, FC and Alhamo, MA and Shao, L and Saif, LJ and Rajashekara, G}, title = {Impact of nutrition and rotavirus infection on the infant gut microbiota in a humanized pig model.}, journal = {BMC gastroenterology}, volume = {18}, number = {1}, pages = {93}, pmid = {29929472}, issn = {1471-230X}, support = {R01 AI099451/AI/NIAID NIH HHS/United States ; AI099451//National Institutes of Health/ ; }, mesh = {Animals ; Diarrhea/microbiology/virology ; Disease Susceptibility ; Feces/microbiology ; Gastroenteritis/*complications/*microbiology/virology ; *Gastrointestinal Microbiome ; Humans ; Infant ; Intestines/microbiology ; Malnutrition/*complications/*microbiology/virology ; RNA, Ribosomal, 16S ; Rotavirus Infections/*complications/*microbiology/virology ; Sequence Analysis, RNA ; Swine ; Virus Shedding ; Weight Gain ; }, abstract = {BACKGROUND: Human rotavirus (HRV) is a major cause of viral gastroenteritis in infants; particularly in developing countries where malnutrition is prevalent. Malnutrition perturbs the infant gut microbiota leading to sub-optimal functioning of the immune system and further predisposing infants to enteric infections. Therefore, we hypothesized that malnutrition exacerbates rotavirus disease severity in infants.<br><br>METHODS: In the present study, we used a neonatal germ free (GF) piglets transplanted with a two-month-old human infant's fecal microbiota (HIFM) on protein deficient and sufficient diets. We report the effects of malnourishment on the HRV infection and the HIFM pig microbiota in feces, intestinal and systemic tissues, using MiSeq 16S gene sequencing (V4-V5 region).<br><br>RESULTS: Microbiota analysis indicated that the HIFM transplantation resulted in a microbial composition in pigs similar to that of the original infant feces. This model was then used to understand the interconnections between microbiota diversity, diet, and HRV infection. Post HRV infection, HIFM pigs on the deficient diet had lower body weights, developed more severe diarrhea and increased virus shedding compared to HIFM pigs on sufficient diet. However, HRV induced diarrhea and shedding was more pronounced in non-colonized GF pigs compared to HIFM pigs on either sufficient or deficient diet, suggesting that the microbiota alone moderated HRV infection. HRV infected pigs on sufficient diet showed increased microbiota diversity in intestinal tissues; whereas, greater diversity was observed in systemic tissues of HRV infected pigs fed with deficient diet.<br><br>CONCLUSIONS: These results suggest that proper nourishment improves the microbiota quality in the intestines, alleviates HRV disease and lower probability of systemic translocation of potential opportunistic pathogens/pathobionts. In conclusion, our findings further support the role for microbiota and proper nutrition in limiting enteric diseases.}, }
@article {pmid29927031, year = {2018}, author = {Kaufman, SS and Zhong, XS and Elsabbagh, AM and Bailey, D and Yazigi, NA and Khan, KM and Matsumoto, CS}, title = {Fecal pancreatic elastase-1 in the evaluation of pancreatic function after pediatric intestinal transplantation.}, journal = {Pediatric transplantation}, volume = {}, number = {}, pages = {e13247}, doi = {10.1111/petr.13247}, pmid = {29927031}, issn = {1399-3046}, abstract = {Fat malabsorption is common after SBT. To identify whether anatomic variant transplants differ in occurrence of exocrine pancreatic insufficiency that could contribute to fat malabsorption, we measured FPE repeatedly in 54 recipients of a SBT, ages 6.2 to 320 months. FPE determination most distant from SBT was 6.1 years. Of the 54, 39% received an isolated intestinal graft (native pancreas only), 48% received an en bloc liver-intestinal-pancreas graft (native and graft pancreas), and 13% received a multivisceral graft (graft pancreas only). Initial FPE was normal (>200 μg/g) in 15 of the 54 at a median of 22 (11-61) days after SBT. Recipients of a liver-intestine-pancreas transplant were more likely to have normal FPE within 30 days after SBT than were isolated intestinal or multivisceral transplant recipients (47%, 19%, and 0%, respectively, P = .049). Of the remaining 39 patients, 34 eventually demonstrated a normal FPE at a median of 168 (31-943) days after SBT. Type of SBT did not influence the likelihood of achieving a normal FPE level or time when it occurred. Five (9%) patients failed to achieve normal FPE, including 3 who died within 2 years after SBT. In conclusion, possessing both graft and native pancreas as in transplantation of an en bloc liver-intestinal-pancreas graft facilitates early normalization of FPE that eventually occurs in most patients irrespective of transplant type. Failure to recover normal pancreatic function may be associated with severe post-transplant complications.}, }
@article {pmid29925252, year = {2018}, author = {Wright, ML and Fournier, C and Houser, MC and Tansey, M and Glass, J and Hertzberg, VS}, title = {Potential Role of the Gut Microbiome in ALS: A Systematic Review.}, journal = {Biological research for nursing}, volume = {20}, number = {5}, pages = {513-521}, doi = {10.1177/1099800418784202}, pmid = {29925252}, issn = {1552-4175}, mesh = {Adult ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/*microbiology/*physiopathology ; Animals ; Disease Models, Animal ; Disease Progression ; Dysbiosis/*etiology/*physiopathology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/*microbiology ; Male ; Mice ; Middle Aged ; }, abstract = {Amyotrophic lateral sclerosis (ALS) etiology and pathophysiology are not well understood. Recent data suggest that dysbiosis of gut microbiota may contribute to ALS etiology and progression. This review aims to explore evidence of associations between gut microbiota and ALS etiology and pathophysiology. Databases were searched for publications relevant to the gut microbiome in ALS. Three publications provided primary evidence of changes in microbiome profiles in ALS. An ALS mouse model revealed damaged tight junction structure and increased permeability in the intestine versus controls along with a shifted microbiome profile, including decreased levels of butyrate-producing bacteria. In a subsequent publication, again using an ALS mouse model, researchers showed that dietary supplementation with butyrate relieved symptoms and lengthened both time to onset of weight loss and survival time. In a small study of ALS patients and healthy controls, investigators also found decreased levels of butyrate-producing bacteria. Essential for maintaining gut barrier integrity, butyrate is the preferred energy source of intestinal epithelial cells. Ten other articles were reviews and commentaries providing indirect support for a role of gut microbiota in ALS pathophysiology. Thus, these studies provide a modicum of evidence implicating gut microbiota in ALS disease, although more research is needed to confirm the connection and determine pathophysiologic mechanisms. Nurses caring for these patients need to understand the gut microbiome and its potential role in ALS in order to effectively counsel patients and their families about emerging therapies (e.g., prebiotics, probiotics, and fecal microbial transplant) and their off-label uses.}, }
@article {pmid29920927, year = {2019}, author = {Lee, JR and Magruder, M and Zhang, L and Westblade, LF and Satlin, MJ and Robertson, A and Edusei, E and Crawford, C and Ling, L and Taur, Y and Schluter, J and Lubetzky, M and Dadhania, D and Pamer, E and Suthanthiran, M}, title = {Gut microbiota dysbiosis and diarrhea in kidney transplant recipients.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {19}, number = {2}, pages = {488-500}, pmid = {29920927}, issn = {1600-6143}, support = {K23 AI124464/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R37 AI051652/AI/NIAID NIH HHS/United States ; //Chinese American Medical Society/International ; }, mesh = {Adult ; Bacteria/genetics/*growth &amp; development/isolation &amp; purification ; Case-Control Studies ; Cohort Studies ; Diarrhea/*etiology/pathology ; Dysbiosis/*etiology/pathology ; Feces/microbiology ; Female ; Follow-Up Studies ; *Gastrointestinal Microbiome ; Glomerular Filtration Rate ; Graft Rejection/*etiology/pathology ; Graft Survival ; Humans ; Kidney Failure, Chronic/*surgery ; Kidney Function Tests ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Postoperative Complications ; Prognosis ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; }, abstract = {Posttransplant diarrhea is associated with kidney allograft failure and death, but its etiology remains unknown in the majority of cases. Because altered gut microbial ecology is a potential basis for diarrhea, we investigated whether posttransplant diarrhea is associated with gut dysbiosis. We enrolled 71 kidney allograft recipients for serial fecal specimen collections in the first 3 months of transplantation and profiled the gut microbiota using 16S ribosomal RNA (rRNA) gene V4-V5 deep sequencing. The Shannon diversity index was significantly lower in 28 diarrheal fecal specimens from 25 recipients with posttransplant diarrhea than in 112 fecal specimens from 46 recipients without posttransplant diarrhea. We found a lower relative abundance of 13 commensal genera (Benjamini-Hochberg adjusted P ≤ .15) in the diarrheal fecal specimens including the same 4 genera identified in our prior study. The 28 diarrheal fecal specimens were also evaluated by a multiplexed polymerase chain reaction (PCR) assay for 22 bacterial, viral, and protozoan gastrointestinal pathogens, and 26 specimens were negative for infectious etiologies. Using PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) to predict metagenomic functions, we found that diarrheal fecal specimens had a lower abundance of metabolic genes. Our findings suggest that posttransplant diarrhea is not associated with common infectious diarrheal pathogens but with a gut dysbiosis.}, }
@article {pmid29920643, year = {2019}, author = {De Luca, F and Shoenfeld, Y}, title = {The microbiome in autoimmune diseases.}, journal = {Clinical and experimental immunology}, volume = {195}, number = {1}, pages = {74-85}, pmid = {29920643}, issn = {1365-2249}, mesh = {Animals ; Autoimmune Diseases/immunology/*microbiology ; Dysbiosis/*immunology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Homeostasis ; Humans ; Immunity, Innate ; Microbiota/*immunology ; Probiotics/*therapeutic use ; }, abstract = {The microbiome is represented by microorganisms which live in a symbiotic way with the mammalian. Microorganisms have the ability to influence different physiological aspects such as the immune system, metabolism and behaviour. In recent years, several studies have highlighted the role of the microbiome in the pathogenesis of autoimmune diseases. Notably, in systemic lupus erythematosus an alteration of the intestinal flora (lower Firmicutes/Bacteroidetes ratio) has been described. Conversely, changes to the gut commensal and periodontal disease have been proposed as important factors in the pathogenesis of rheumatoid arthritis. At the same time, other autoimmune diseases (i.e. systemic sclerosis, Sjögren's syndrome and anti-phospholipid syndrome) also share modifications of the microbiome in the intestinal tract and oral flora. Herein, we describe the role of the microbiome in the maintenance homeostasis of the immune system and then the alterations of the microorganisms that occur in systemic autoimmune diseases. Finally, we will consider the use of probiotics and faecal transplantation as novel therapeutic targets.}, }
@article {pmid29915396, year = {2018}, author = {Koretz, RL}, title = {Probiotics in Gastroenterology: How Pro Is the Evidence in Adults?.}, journal = {The American journal of gastroenterology}, volume = {113}, number = {8}, pages = {1125-1136}, doi = {10.1038/s41395-018-0138-0}, pmid = {29915396}, issn = {1572-0241}, mesh = {Adult ; Gastroenterology ; Gastrointestinal Diseases/*drug therapy ; Humans ; Practice Guidelines as Topic ; Probiotics/*therapeutic use ; Randomized Controlled Trials as Topic ; }, abstract = {Probiotic usage has become popular with both medical practitioners and the community in general; patients commonly seek advice regarding what, if any, such preparation would be useful for their own diseases. Since such advice should be evidence-based, identified randomized clinical trials (RCTs) for a number of gastrointestinal conditions were reviewed; the data were organized by individual probiotic genera/species. Only trials in adults were considered. Most of the identified RCTs were small and low-quality, so any conclusions to be drawn will be limited at least by methodologic problems. Using the GRADE system to consider the reliability of the evidence generated from these RCTs, it did appear that the use of fecal microbial transplantation to treat recurrent Clostridium difficile infection is well justified. Given the methodologic issues, there was moderately good evidence for preventing antibiotic-associated diarrhea with Lactobacillus, Bifidobacterium, Streptococcus, or Saccharomyces boulardii and for using Lactobacillus, Bifidobacterium, or Saccharomyces as adjunct therapy in the treatment of Helicobacter pylori. There were other conditions for which some supportive evidence was available. These conditions include VSL#3 for maintaining remissions in patients with pouchitis or treating active ulcerative colitis (UC), fecal microbial transplantation for treating active UC, Bifidobacterium for treating patients with UC in remission, Lactobacillus in patients with painful diverticulosis, a variety of probiotics (Lactobacillus, Bifidobacterium, Streptococcus, or VSL#3) in patients with minimal hepatic encephalopathy, and providing synbiotics to patients postoperatively after liver transplantation. Unfortunately, other limitations in the evidence made it very likely that future research will have an effect on the estimated benefit; these interventions cannot yet be recommended for routine use.}, }
@article {pmid29914912, year = {2018}, author = {Hota, SS and Poutanen, SM}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {190}, number = {24}, pages = {E746}, pmid = {29914912}, issn = {1488-2329}, mesh = {Clostridioides difficile/*pathogenicity ; Disease Management ; Enterocolitis, Pseudomembranous/complications/microbiology/*therapy ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Tract/*microbiology ; Humans ; Practice Guidelines as Topic ; Recurrence ; Treatment Outcome ; }, }
@article {pmid29912755, year = {2018}, author = {Rizzatti, G and Ianiro, G and Gasbarrini, A}, title = {Antibiotic and Modulation of Microbiota: A New Paradigm?.}, journal = {Journal of clinical gastroenterology}, volume = {52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition &amp; Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017}, number = {}, pages = {S74-S77}, doi = {10.1097/MCG.0000000000001069}, pmid = {29912755}, issn = {1539-2031}, mesh = {Anti-Bacterial Agents/*adverse effects ; Dysbiosis/chemically induced/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Humans ; Probiotics/*therapeutic use ; }, abstract = {Recently new insights on gut microbiota have revolutionized many concepts of the modern medicine. The alteration of microbiota, which is called dysbiosis, has been associated with an expanding list of diseases and conditions. The development of next-generation sequencing techniques allowed comprehensive analysis of gut microbiota composition without the limitations of classic culture methods. Furthermore, introduction of functional techniques such as metabolomics and proteomics allowed for integrated analysis thus obtaining more robust insights on microbiota functions in health and disease. These tools allow to address the role of factors able to modify the gut microbiota, the so called "microbiota influencers." These data are useful to explain the physiopathology of several disease and thus to identify new potential therapeutic targets. Among microbiota influencers, many studies focused on the impact of antibiotic administration on the gut microbiota, because of their widespread use. Notably, beside the known beneficial effect of antibiotic in treating infectious diseases, these drugs have shown detrimental effects on gut microbiota which, in turn, might have long-term consequences on the host. Finally, therapeutic modulation of gut microbiota, by means of selected antibiotics with eubiotic effects, probiotics and with fecal microbiota transplantation seems of great interest as it might be able to prevent or even revert antibiotic-induced dysbiosis.}, }
@article {pmid29910564, year = {2018}, author = {Duarte-Chavez, R and Wojda, TR and Zanders, TB and Geme, B and Fioravanti, G and Stawicki, SP}, title = {Early Results of Fecal Microbial Transplantation Protocol Implementation at a Community-based University Hospital.}, journal = {Journal of global infectious diseases}, volume = {10}, number = {2}, pages = {47-57}, pmid = {29910564}, issn = {0974-777X}, abstract = {INTRODUCTION: Clostridium difficile (CD) is a serious and increasingly prevalent healthcare-associated infection. The pathogenesis of CD infection (CDI) involves the acquisition of CD with a concurrent disruption of the native gut flora. Antibiotics are a major risk although other contributing factors have also been identified. Clinical management combines discontinuation of the offending antibiotic, initiation of CD-specific antibiotic therapy, probiotic agent use, fecal microbiota transplantation (FMT), and surgery as the "last resort" option. The aim of this study is to review short-term clinical results following the implementation of FMT protocol (FMTP) at our community-based university hospital.<br><br>METHODS: After obtaining Institutional Review Board and Infection Control Committee approvals, we implemented an institution-wide FMTP for patients diagnosed with CDI. Prospective tracking of all patients receiving FMT between July 1, 2015, and February 1, 2017, was conducted using REDCap&#x2122; electronic data capture system. According to the FMTP, indications for FMT included (a) three or more CDI recurrences, (b) two or more hospital admissions with severe CDI, or (c) first episode of complicated CDI (CCDI). Risk factors for initial infection and for treatment failure were assessed. Patients were followed for at least 3 months to monitor for cure/failure, relapse, and side effects. Frozen 250 mL FMT samples were acquired from OpenBiome (Somerville, MA, USA). After 4 h of thawing, the liquid suspension was applied using colonoscopy, beginning with terminal ileum and proceeding distally toward mid-transverse colon. Monitored clinical parameters included disease severity (Hines VA CDI Severity Score or HVCSS), concomitant medications, number of FMT treatments, non-FMT therapies, cure rates, and mortality. Descriptive statistics were utilized to outline the study results.<br><br>RESULTS: A total of 35 patients (mean age 58.5 years, 69% female) were analyzed, with FMT-attributable primary cure achieved in 30/35 (86%) cases. Within this subgroup, 2/30 (6.7%) patients recurred and were subsequently cured with long-term oral vancomycin. Among five primary FMT failures (14% total sample), 3 (60%) achieved medical cure with long-term oral vancomycin therapy and 2 (40%) required colectomy. For the seven patients who either failed FMT or recurred, long-term vancomycin therapy was curative in all but two cases. For patients with severe CDI (HVCSS &#x2265;3), primary and overall cure rates were 6/10 (60%) and 8/10 (80%), respectively. Patients with CCDI (n = 4) had higher HVCSS (4 vs. 3) and a mortality of 25%. Characteristics of patients who failed initial FMT included older age (70 vs. 57 years), female sex (80% vs. 67%), severe CDI (80% vs. 13%), and active opioid use during the initial infection (60% vs. 37%) and at the time of FMT (60% vs. 27%). The most commonly reported side effect of FMT was loose stools.<br><br>CONCLUSIONS: This pilot study supports the efficacy and safety of FMT administration for CDI in the setting of a community-based university hospital. Following FMTP implementation, primary (86%) and overall (94%) nonsurgical cure rates were similar to those reported in other studies. The potential role of opioids as a modulator of CDI warrants further clinical investigation.}, }
@article {pmid29910467, year = {2018}, author = {Soto, M and Herzog, C and Pacheco, JA and Fujisaka, S and Bullock, K and Clish, CB and Kahn, CR}, title = {Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism.}, journal = {Molecular psychiatry}, volume = {23}, number = {12}, pages = {2287-2301}, pmid = {29910467}, issn = {1476-5578}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; R01 DK055545/DK/NIDDK NIH HHS/United States ; P30 DK036836/DK/NIDDK NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; R01 DK033201/DK/NIDDK NIH HHS/United States ; R37 DK031036/DK/NIDDK NIH HHS/United States ; R01 DK031036/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents ; Anxiety ; Brain/metabolism ; Diet, High-Fat ; Gastrointestinal Microbiome/genetics/*physiology ; Inflammation/metabolism ; Insulin/metabolism ; Insulin Resistance/physiology ; Male ; Metronidazole/pharmacology ; Mice ; Mice, Inbred C57BL ; Microbiota ; Obesity/*metabolism/microbiology ; RNA, Ribosomal, 16S/drug effects/genetics ; Vancomycin/pharmacology ; }, abstract = {Obesity and diabetes in humans are associated with increased rates of anxiety and depression. To understand the role of the gut microbiome and brain insulin resistance in these disorders, we evaluated behaviors and insulin action in brain of mice with diet-induced obesity (DIO) with and without antibiotic treatment. We find that DIO mice have behaviors reflective of increased anxiety and depression. This is associated with decreased insulin signaling and increased inflammation in in the nucleus accumbens and amygdala. Treatment with oral metronidazole or vancomycin decreases inflammation, improves insulin signaling in the brain and reduces signs of anxiety and depression. These effects are associated with changes in the levels of tryptophan, GABA, BDNF, amino acids, and multiple acylcarnitines, and are transferable to germ-free mice by fecal transplant. Thus, changes in gut microbiota can control brain insulin signaling and metabolite levels, and this leads to altered neurobehaviors.}, }
@article {pmid29909020, year = {2018}, author = {Chen, L and He, Z and Iuga, AC and Martins Filho, SN and Faith, JJ and Clemente, JC and Deshpande, M and Jayaprakash, A and Colombel, JF and Lafaille, JJ and Sachidanandam, R and Furtado, GC and Lira, SA}, title = {Diet Modifies Colonic Microbiota and CD4[+] T-Cell Repertoire to Induce Flares of Colitis in Mice With Myeloid-Cell Expression of Interleukin 23.}, journal = {Gastroenterology}, volume = {155}, number = {4}, pages = {1177-1191.e16}, pmid = {29909020}, issn = {1528-0012}, support = {R01 CA161373/CA/NCI NIH HHS/United States ; R01 DK110352/DK/NIDDK NIH HHS/United States ; }, mesh = {Adoptive Transfer ; *Animal Feed ; Animals ; CD4-Positive T-Lymphocytes/immunology/*metabolism/transplantation ; CX3C Chemokine Receptor 1/metabolism ; Colitis/*diet therapy/immunology/metabolism/microbiology ; Colon/immunology/*metabolism/microbiology ; Disease Models, Animal ; Disease Progression ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gene-Environment Interaction ; Host-Pathogen Interactions ; Interleukin-23/genetics/*metabolism ; Mice, Inbred C57BL ; Mice, Transgenic ; Myeloid Cells/*metabolism ; Nutritive Value ; Signal Transduction ; Time Factors ; }, abstract = {BACKGROUND &amp; AIMS: Several studies have shown that signaling via the interleukin 23 (IL23) receptor is required for development of colitis. We studied the roles of IL23, dietary factors, alterations to the microbiota, and T cells in the development and progression of colitis in mice.<br><br>METHODS: All mice were maintained on laboratory diet 5053, unless otherwise noted. We generated mice that express IL23 in CX3CR1-positive myeloid cells (R23FR mice) upon cyclic administration of tamoxifen dissolved in diet 2019. Diets 2019 and 5053 have minor differences in the overall composition of protein, fat, fiber, minerals, and vitamins. CX3CR1[CreER] mice (FR mice) were used as controls. Some mice were given antibiotics, and others were raised in a germ-free environment. Intestinal tissues were collected and analyzed by histology and flow cytometry. Feces were collected and analyzed by 16S rDNA sequencing. Feces from C57/Bl6, R23FR, or FR mice were fed to FR and R23FR germ-free mice in microbiota transplant experiments. We also performed studies with R23FR/Rag[-/-], R23FR/Mu[-/-], and R23FR/Tcrd[-/-] mice. R23FR mice were given injections of antibodies against CD4 or CD8 to deplete T cells. Mesenteric lymph nodes and large intestine CD4[+] cells from R23FR or FR mice in remission from colitis were transferred into Rag[-/-] mice. CD4[+] cells were isolated from donor R23FR mice and recipient Rag[-/-] mice, and T-cell receptor sequences were determined.<br><br>RESULTS: Expression of IL23 led to development of a relapsing-remitting colitis that was dependent on the microbiota and CD4[+] T cells. The relapses were caused by switching from the conventional diet used in our facility (diet 5053) to the diet 2019 and were not dependent on tamoxifen after the first cycle. The switch in the diet modified the microbiota but did not alter levels of IL23 in intestinal tissues compared with mice that remained on the conventional diet. Mesenteric lymph nodes and large intestine CD4[+] cells from R23FR mice in remission, but not from FR mice, induced colitis after transfer into Rag[-/-] mice, but only when these mice were placed on the diet 2019. The CD4[+] T-cell receptor repertoire of Rag[-/-] mice with colitis (fed the 2019 diet) was less diverse than that from donor mice and Rag[-/-] mice without colitis (fed the 5053 diet) because of expansion of dominant T-cell clones.<br><br>CONCLUSIONS: We developed mice that express IL23 in CX3CR1-positive myeloid cells (R23FR mice) and found that they are more susceptible to diet-induced colitis than mice that do not express IL23. The R23FR mice have a population of CD4[+] T cells that becomes activated in response to dietary changes and alterations to the intestinal microbiota. The results indicate that alterations in the diet, intestinal microbiota, and IL23 signaling can contribute to pathogenesis of inflammatory bowel disease.}, }
@article {pmid29908957, year = {2019}, author = {Veraldi, S and Angileri, L and Rossi, LC}, title = {Chronic urticaria revealing amebiasis.}, journal = {Travel medicine and infectious disease}, volume = {27}, number = {}, pages = {133}, doi = {10.1016/j.tmaid.2018.06.011}, pmid = {29908957}, issn = {1873-0442}, mesh = {Amebiasis/complications/*diagnosis ; Antiprotozoal Agents/therapeutic use ; Entamoeba histolytica/isolation &amp; purification ; Ethiopia ; Feces/parasitology ; Female ; Humans ; Metronidazole/therapeutic use ; Middle Aged ; Travel-Related Illness ; Treatment Outcome ; Urticaria/*diagnosis/drug therapy/etiology ; }, }
@article {pmid29904348, year = {2018}, author = {Cui, H and Cai, Y and Wang, L and Jia, B and Li, J and Zhao, S and Chu, X and Lin, J and Zhang, X and Bian, Y and Zhuang, P}, title = {Berberine Regulates Treg/Th17 Balance to Treat Ulcerative Colitis Through Modulating the Gut Microbiota in the Colon.}, journal = {Frontiers in pharmacology}, volume = {9}, number = {}, pages = {571}, pmid = {29904348}, issn = {1663-9812}, abstract = {Berberine (BBR), an alkaloid isolated from Rhizoma Coptidis, Cortex Phellode, and Berberis, has been widely used in the treatment of ulcerative colitis (UC). However, the mechanism of BBR on UC is unknown. In this study, we investigated the activities of T regulatory cell (Treg) and T helper 17 cell (Th17) in a dextran sulfate sodium (DSS)-induced UC mouse model after BBR administration. We also investigated the changes of gut microbiota composition using 16S rRNA analysis. We also examined whether BBR could regulate the Treg/Th17 balance by modifying gut microbiota. The mechanism was further confirmed by depleting gut microbiota through a combination of antibiotic treatment and fecal transplantations. Results showed that BBR treatment could improve the Treg/Th17 balance in the DSS-induced UC model. BBR also reduced diversity of the gut microbiota and interfered with the relative abundance of Desulfovibrio, Eubacterium, and Bacteroides. Moreover, BBR treatment did not influence the Treg/Th17 balance after the depletion of gut microbiota. Our results also revealed that fecal transplantation from BBR-treated mice could relieve UC and regulate the Treg/Th17 balance. In conclusion, our study provides evidence that BBR prevents UC by modifying gut microbiota and regulating the balance of Treg/Th17.}, }
@article {pmid29903041, year = {2018}, author = {Zhao, L and Huang, Y and Lu, L and Yang, W and Huang, T and Lin, Z and Lin, C and Kwan, H and Wong, HLX and Chen, Y and Sun, S and Xie, X and Fang, X and Yang, H and Wang, J and Zhu, L and Bian, Z}, title = {Saturated long-chain fatty acid-producing bacteria contribute to enhanced colonic motility in rats.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {107}, pmid = {29903041}, issn = {2049-2618}, support = {FRG2/15-16/001, FRG2/16-17/003//Faculty Research Grant of Hong Kong Baptist University/International ; C2012-15G//The Research Grants Council of Hong Kong Collaborative Research Fund/International ; 2016A050503039//Guangdong-Hong Kong Technology Cooperation Funding Scheme/International ; }, mesh = {Animals ; Bacteroidetes/*metabolism ; Biodiversity ; Colon/microbiology/physiology ; Disease Models, Animal ; Dysbiosis/microbiology ; Fatty Acids/*analysis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Gastrointestinal Motility/*physiology ; Gastrointestinal Tract/microbiology ; Germ-Free Life ; Lactobacillus/*metabolism ; Maternal Deprivation ; Muscle Contraction/physiology ; Prevotella/*metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: The gut microbiota is closely associated with gastrointestinal (GI) motility disorder, but the mechanism(s) by which bacteria interact with and affect host GI motility remains unclear. In this study, through using metabolomic and metagenomic analyses, an animal model of neonatal maternal separation (NMS) characterized by accelerated colonic motility and gut dysbiosis was used to investigate the mechanism underlying microbiota-driven motility dysfunction.<br><br>RESULTS: An excess of intracolonic saturated long-chain fatty acids (SLCFAs) was associated with enhanced bowel motility in NMS rats. Heptadecanoic acid (C17:0) and stearic acid (C18:0), as the most abundant odd- and even-numbered carbon SLCFAs in the colon lumen, can promote rat colonic muscle contraction and increase stool frequency. Increase of SLCFAs was positively correlated with elevated abundances of Prevotella, Lactobacillus, and Alistipes. Functional annotation found that the level of bacterial LCFA biosynthesis was highly enriched in NMS group. Essential synthetic genes Fabs were largely identified from the genera Prevotella, Lactobacillus, and Alistipes. Pseudo germ-free (GF) rats receiving fecal microbiota from NMS donors exhibited increased defecation frequency and upregulated bacterial production of intracolonic SLCFAs. Modulation of gut dysbiosis by neomycin effectively attenuated GI motility and reduced bacterial SLCFA generation in the colon lumen of NMS rats.<br><br>CONCLUSIONS: These findings reveal a previously unknown relationship between gut bacteria, intracolonic SLCFAs, and host GI motility, suggesting the importance of SLCFA-producing bacteria in GI motility disorders. Further exploration of this relationship could lead to a precise medication targeting the gut microbiota for treating GI motility disorders.}, }
@article {pmid29901551, year = {2018}, author = {Bulik-Sullivan, EC and Roy, S and Elliott, RJ and Kassam, Z and Lichtman, SN and Carroll, IM and Gulati, AS}, title = {Intestinal Microbial and Metabolic Alterations Following Successful Fecal Microbiota Transplant for D-Lactic Acidosis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {67}, number = {4}, pages = {483-487}, doi = {10.1097/MPG.0000000000002043}, pmid = {29901551}, issn = {1536-4801}, mesh = {Acidosis, Lactic/blood/microbiology/*therapy ; Child ; Fecal Microbiota Transplantation/*methods ; Female ; *Gastrointestinal Microbiome ; Humans ; Lactic Acid/*blood ; Short Bowel Syndrome/blood/*complications/microbiology ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) involves the transfer of stool from a healthy individual into the intestinal tract of a diseased recipient. Although used primarily for recurrent Clostridium difficile infection, FMT is increasingly being attempted as an experimental therapy for other illnesses, including metabolic disorders. D-lactic acidosis (D-LA) is a metabolic disorder that may occur in individuals with short bowel syndrome when lactate-producing bacteria in the colon overproduce D-lactate. This results in elevated systemic levels of D-lactate, metabolic acidosis, and encephalopathy. In this study, we report the successful use of FMT for the treatment of recurrent D-LA in a child who was unresponsive to conventional therapies. Importantly, we also present profiles of the enteric microbiota, as well as fecal D-/L-lactic acid metabolites, before and longitudinally after FMT. These data provide valuable insight into the putative mechanisms of D-LA pathogenesis and its treatment.}, }
@article {pmid29896165, year = {2018}, author = {Valenzuela, MJ and Caruffo, M and Herrera, Y and Medina, DA and Coronado, M and Feijóo, CG and Muñoz, S and Garrido, D and Troncoso, M and Figueroa, G and Toro, M and Reyes-Jara, A and Magne, F and Navarrete, P}, title = {Evaluating the Capacity of Human Gut Microorganisms to Colonize the Zebrafish Larvae (Danio rerio).}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1032}, pmid = {29896165}, issn = {1664-302X}, support = {T37 MD001425/MD/NIMHD NIH HHS/United States ; }, abstract = {In this study we evaluated if zebrafish larvae can be colonized by human gut microorganisms. We tested two strategies: (1) through transplantation of a human fecal microbiota and (2) by successively transplanting aerotolerant anaerobic microorganisms, similar to the colonization in the human intestine during early life. We used conventionally raised zebrafish larvae harboring their own aerobic microbiota to improve the colonization of anaerobic microorganisms. The results showed with the fecal transplant, that some members of the human gut microbiota were transferred to larvae. Bacillus, Roseburia, Prevotella, Oscillospira, one unclassified genus of the family Ruminococcaceae and Enterobacteriaceae were detected in 3 days post fertilization (dpf) larvae; however only Bacillus persisted to 7 dpf. Successive inoculation of Lactobacillus, Bifidobacterium and Clostridioides did not improve their colonization, compared to individual inoculation of each bacterial species. Interestingly, the sporulating bacteria Bacillus clausii and Clostridioides difficile were the most persistent microorganisms. Their endospores persisted at least 5 days after inoculating 3 dpf larvae. However, when 5 dpf larvae were inoculated, the proportion of vegetative cells in larvae increased, revealing proliferation of the inoculated bacteria and better colonization of the host. In conclusion, these results suggest that it is feasible to colonize zebrafish larvae with some human bacteria, such as C. difficile and Bacillus and open an interesting area to study interactions between these microorganisms and the host.}, }
@article {pmid29895922, year = {2018}, author = {Reardon, S}, title = {Faecal transplants could help preserve vulnerable species.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {173-174}, doi = {10.1038/d41586-018-05352-1}, pmid = {29895922}, issn = {1476-4687}, mesh = {Animals ; Animals, Wild/microbiology ; Animals, Zoo/microbiology ; Anura/microbiology ; Conservation of Natural Resources/*methods ; Diet/*veterinary ; *Endangered Species ; Eucalyptus ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Food Preferences ; Gastrointestinal Microbiome/*physiology ; Male ; Mycoses/microbiology/prevention &amp; control/veterinary ; Perissodactyla/*microbiology/physiology ; Phascolarctidae/*microbiology/physiology ; Survival Rate ; }, }
@article {pmid29895255, year = {2019}, author = {Katsi, V and Didagelos, M and Skevofilax, S and Armenis, I and Kartalis, A and Vlachopoulos, C and Karvounis, H and Tousoulis, D}, title = {GUT Microbiome-GUT Dysbiosis-Arterial Hypertension: New Horizons.}, journal = {Current hypertension reviews}, volume = {15}, number = {1}, pages = {40-46}, doi = {10.2174/1573402114666180613080439}, pmid = {29895255}, issn = {1875-6506}, mesh = {Animals ; Antihypertensive Agents/therapeutic use ; *Arterial Pressure/drug effects ; Bacteria/drug effects/*growth &amp; development ; Disease Models, Animal ; Dysbiosis ; *Gastrointestinal Microbiome/drug effects ; Host-Pathogen Interactions ; Humans ; Hypertension/drug therapy/epidemiology/*microbiology/*physiopathology ; Intestines/*microbiology ; Probiotics/therapeutic use ; Risk Factors ; }, abstract = {Arterial hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. The human microbiome refers to the community of microorganisms that live in or on the human body. They influence human physiology by interfering in several processes such as providing nutrients and vitamins in Phase I and Phase II drug metabolism. The human gut microbiota is represented mainly by Firmicutes and Bacteroidetes and to a lesser degree by Actinobacteria and Proteobacteria, with each individual harbouring at least 160 such species. Gut microbiota contributes to blood pressure homeostasis and the pathogenesis of arterial hypertension through production, modification, and degradation of a variety of microbial-derived bioactive metabolites. Animal studies and to a lesser degree human research has unmasked relative mechanisms, mainly through the effect of certain microbiome metabolites and their receptors, outlining this relationship. Interventions to utilize these pathways, with probiotics, prebiotics, antibiotics and fecal microbiome transplantation have shown promising results. Personalized microbiome-based disease prediction and treatment responsiveness seem futuristic. Undoubtedly, a long way of experimental and clinical research should be pursued to elucidate this novel, intriguing and very promising horizon.}, }
@article {pmid29890556, year = {2018}, author = {Bruensing, J and Buendgens, L and Jochum, C and Herbers, U and Canbay, A and Braun, G and Trautwein, C and Huber, W and Koch, A and Tacke, F}, title = {[Management of Clostridium difficile infections at German intensive care units - results from a survey among intensivists].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {56}, number = {6}, pages = {551-560}, doi = {10.1055/s-0044-102103}, pmid = {29890556}, issn = {1439-7803}, mesh = {*Clostridioides difficile ; *Clostridium Infections/diagnosis/mortality/therapy ; Germany ; *Guideline Adherence ; Humans ; Intensive Care Units ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Clostridium difficile associated colitis is a frequent cause of nosocomial diarrhea at the intensive care unit (ICU) and is associated with poor prognosis in critically ill patients. Few studies have evaluated the efficacy of treatment options or adherence to guideline recommendations of Clostridium difficile infections at the ICU.<br><br>METHODS: Therefore, on behalf of the Gastroenterology Intensive Care Medicine working group of the DGVS, we have conducted an online-based survey among leading intensivists in Germany.<br><br>RESULTS: Out of the 351 invited, 85 (24.2&#x200a;%), primarily leading executive physicians at primary to tertiary care hospitals, completed the survey. They reported standardized diagnostic algorithms of 79.3&#x200a;%, in line with current guideline recommendations (i.&#x200a;e., toxin testing in stool, possibly GDH screening, and endoscopy). First-line therapy of Clostridium difficile infections at the ICU was reported to be oral vancomycin in 48.3&#x200a;% and oral metronidazole in 34.5&#x200a;%. The success of first-line therapy was estimated at 67&#x200a;% for clinical cure, 15&#x200a;% persisting colitis, 5&#x200a;% sepsis or megacolon, 10&#x200a;% recurrence, and 3&#x200a;% death. Hospitals of primary/secondary care more often used metronidazole compared to university hospitals. Standard treatments for recurrent infection were vancomycin orally (40&#x200a;% alone, 29.1&#x200a;% combined with metronidazole) or, more rarely, fidaxomicin (25.5&#x200a;%). Fidaxomicin has been used at least once at the ICU in 79&#x200a;% of the respondents. Eleven percent have used fecal microbiota transplant (FMT) in selected cases at the ICU.<br><br>CONCLUSION: Our survey indicated a high awareness of German intensivists for Clostridium difficile infections, but also marked differences in local therapeutic algorithms, especially in first-line treatment.}, }
@article {pmid29889838, year = {2018}, author = {Hullar, MAJ and Lampe, JW and Torok-Storb, BJ and Harkey, MA}, title = {The canine gut microbiome is associated with higher risk of gastric dilatation-volvulus and high risk genetic variants of the immune system.}, journal = {PloS one}, volume = {13}, number = {6}, pages = {e0197686}, pmid = {29889838}, issn = {1932-6203}, support = {P30 DK056465/DK/NIDDK NIH HHS/United States ; U54 DK106829/DK/NIDDK NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Breeding ; Dog Diseases/genetics/immunology/*microbiology ; Dogs ; Female ; Gastric Dilatation/genetics/immunology/microbiology ; Gastrointestinal Microbiome/genetics/*immunology ; Genetic Variation ; Immune System/*immunology/microbiology ; Male ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; Stomach Volvulus/genetics/immunology/microbiology ; }, abstract = {BACKGROUND: Large and giant dog breeds have a high risk for gastric dilatation-volvulus (GDV) which is an acute, life-threatening condition. Previous work by our group identified a strong risk of GDV linked to specific alleles in innate and adaptive immune genes. We hypothesize that variation in the genes of the immune system act through modulation of the gut microbiome, or through autoimmune mechanisms, or both, to predispose dogs to this condition. Here, we investigate whether differences in the canine fecal microbiome are associated with GDV and are linked to previously identified risk alleles.<br><br>Fecal samples from healthy Great Danes (n = 38), and dogs with at least one occurrence of GDV (n = 37) were collected and analyzed by paired-end sequencing of the 16S rRNA gene. Dietary intake and temperament were estimated from a study-specific dietary and temperament questionnaire. Dogs with GDV had significantly more diverse fecal microbiomes than healthy control dogs. Alpha diversity was significantly increased in dogs with GDV, as well as dogs with at least one risk allele for DRB1 and TRL5. We found no significant association of dietary intake and GDV. Dogs with GDV showed a significant expansion of the rare lineage Actinobacteria (p = 0.004), as well as a significantly greater abundance of Firmicutes (p = 0.004) and a significantly lower abundance of Bacteroidetes (p<0.004). There was a significant difference in the abundance of 10 genera but after correction for multiple comparisons, none were significant. Bacterial phyla were significantly different between controls and dogs with GDV and at least one risk allele for DRB1 and TRL5. Actinobacteria were significantly higher in dogs with GDV and with one risk allele for DRB1 and TLR5 but not DLA88 genes. Furthermore, Collinsella was significantly increased in dogs with at least one risk allele for DRB1 and TLR5. Logistic regression showed that a model which included Actinobacteria, at least one risk allele,and temperament, explained 29% of the variation in risk of GDV in Great Danes.<br><br>CONCLUSIONS: The microbiome in GDV was altered by an expansion of a minor lineage and was associated with specific alleles of both innate and adaptive immunity genes. These associations are consistent with our hypothesis that immune genes may play a role in predisposition to GDV by altering the gut microbiome. Further research will be required to directly test the causal relationships of immune genes, the gut microbiome and GDV.}, }
@article {pmid29888965, year = {2019}, author = {Aziz, M and Fatima, R and Douglass, LN and Abughanimeh, O and Raza, S}, title = {Current updates in management of Clostridium difficile infection in cancer patients.}, journal = {Current medical research and opinion}, volume = {35}, number = {3}, pages = {473-478}, doi = {10.1080/03007995.2018.1487389}, pmid = {29888965}, issn = {1473-4877}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/*drug therapy ; Diarrhea/complications ; Humans ; Neoplasms/*complications ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is a significant health burden, now recognized as the leading cause of acquired diarrhea in patients receiving antibiotic therapy. Complications of infection with this pathogen include severe diarrhea, causing electrolyte imbalances, dehydration, hemodynamic instability, toxic megacolon, shock, and death. Hence it is extremely paramount to stay updated on management options for this infection, especially in cancer patients.<br><br>REVIEW: This article presents an in-depth review of literature on the treatment modalities available for CDI in cancer patients. Relevant articles highlighting therapeutic and symptomatic management of CDI patients with underlying malignancy have been summarized.<br><br>CONCLUSIONS: Despite the current options available, more studies are needed to assess the newer therapeutic options that are being employed for populations other than cancer patients.}, }
@article {pmid29886561, year = {2018}, author = {Bhutiani, N and Schucht, JE and Miller, KR and McClave, SA}, title = {Technical Aspects of Fecal Microbial Transplantation (FMT).}, journal = {Current gastroenterology reports}, volume = {20}, number = {7}, pages = {30}, pmid = {29886561}, issn = {1534-312X}, mesh = {Donor Selection ; Enterocolitis, Pseudomembranous/therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Patient Selection ; }, abstract = {PURPOSE OF REVIEW: Fecal microbial transplantation (FMT) has become established as an effective therapeutic modality in the treatment of antibiotic-refractory recurrent Clostridium difficile colitis. A number of formulations and methods of delivery of FMT are currently available, each with distinct advantages. This review aims to review donor and patient selection for FMT as well as procedural aspects of FMT to help guide clinical practice.<br><br>RECENT FINDINGS: FMT can be obtained in fresh, frozen, lyophilized, and capsule-based formulations for delivery by oral ingestion, nasoenteric tube, colonoscopy, or enema (depending on the formulation used). Choosing the optimal method relies heavily on patient-related factors, including underlying pathology and severity of illness. As potential applications for FMT expand, careful donor screening and patient selection are critical to minimizing risk to patients and physicians. FMT represents an excellent therapeutic option for treatment of recurrent Clostridium difficile colitis and holds promise as a possible treatment modality in a variety of other conditions. The wide array of delivery methods allows for its application in various disease states in both the inpatient and outpatient setting.}, }
@article {pmid29886457, year = {2018}, author = {Zhan, G and Yang, N and Li, S and Huang, N and Fang, X and Zhang, J and Zhu, B and Yang, L and Yang, C and Luo, A}, title = {Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice.}, journal = {Aging}, volume = {10}, number = {6}, pages = {1257-1267}, pmid = {29886457}, issn = {1945-4589}, mesh = {*Aging ; Animals ; Anti-Bacterial Agents ; Behavior, Animal ; Cognitive Dysfunction/*etiology ; Gastrointestinal Microbiome/*physiology ; Male ; Memory ; Mice ; Mice, Inbred Strains ; Spatial Learning ; }, abstract = {Alzheimer's disease is characterized by cognitive dysfunction and aging is an important predisposing factor; however, the pathological and therapeutic mechanisms are not fully understood. Recently, the role of gut microbiota in Alzheimer's disease has received increasing attention. The cognitive function in senescence-accelerated mouse prone 8 (SAMP8) mice was significantly decreased and the Chao 1 and Shannon indices, principal coordinates analysis, and principal component analysis results were notably abnormal compared with that of those in senescence-accelerated mouse resistant 1 (SAMR1) mice. Moreover, 27 gut bacteria at six phylogenetic levels differed between SAMP8 and SAMR1 mice. In a separate study, we transplanted fecal bacteria from SAMP8 or SAMR1 mice into pseudo germ-free mice. Interestingly, the pseudo germ-free mice had significantly lower cognitive function prior to transplant. Pseudo germ-free mice that received fecal bacteria transplants from SAMR1 mice but not from SAMP8 mice showed improvements in behavior and in α-diversity and β-diversity indices. In total, 14 bacteria at six phylogenetic levels were significantly altered by the gut microbiota transplant. These results suggest that cognitive dysfunction in SAMP8 mice is associated with abnormal composition of the gut microbiota. Thus, improving abnormal gut microbiota may provide an alternative treatment for cognitive dysfunction and Alzheimer's disease.}, }
@article {pmid29884929, year = {2018}, author = {Panchal, P and Budree, S and Scheeler, A and Medina, G and Seng, M and Wong, WF and Elliott, R and Mitchell, T and Kassam, Z and Allegretti, JR and Osman, M}, title = {Correction to: Scaling Safe Access to Fecal Microbiota Transplantation: Past, Present, and Future.}, journal = {Current gastroenterology reports}, volume = {20}, number = {7}, pages = {28}, doi = {10.1007/s11894-018-0634-9}, pmid = {29884929}, issn = {1534-312X}, abstract = {In the original version of this article, author Ryan Elliott's name was misspelled as Ryan Eliott. The correct spelling of the name is Ryan Elliott.}, }
@article {pmid29880966, year = {2018}, author = {Golfeyz, S}, title = {Celiac Disease and Fecal Microbiota Transplantation: A New Beginning?.}, journal = {The American journal of gastroenterology}, volume = {113}, number = {8}, pages = {1256}, doi = {10.1038/s41395-018-0094-8}, pmid = {29880966}, issn = {1572-0241}, mesh = {*Celiac Disease ; *Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid29880353, year = {2018}, author = {Gu, B and Bo, GZ and Ke, C}, title = {Exploration of Fecal Microbiota Transplantation in the Treatment of Refractory Diarrhea After Renal Transplantation.}, journal = {Transplantation proceedings}, volume = {50}, number = {5}, pages = {1326-1331}, doi = {10.1016/j.transproceed.2018.03.013}, pmid = {29880353}, issn = {1873-2623}, mesh = {Adult ; Aged ; Diarrhea/etiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Postoperative Complications/etiology/*therapy ; Prognosis ; Tacrolimus/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Exploration of fecal microbiota transplantation in the treatment of refractory diarrhea after renal transplantation.<br><br>METHODS: Summarize the etiology of 120 cases with diarrhea after renal transplantation from 2014 to 2017 in our hospital. There were 4 recipients of refractory diarrhea who accepted fecal microbiota transplantation with informed consent, and we collected clinical data of stool and bacterial culture, gut microbiota analysis, graft function, electrolytes, immunosuppressant concentrations of prognostic evaluation of patients with fecal transplantation.<br><br>RESULTS: The absorption of electrolyte is slightly higher and concentration of tacrolimus and creatinine were not significantly changed compared with before.<br><br>CONCLUSION: Fecal microbiota transplantation provides a new choice to refractory diarrhea after renal transplantation as an innovative treatment, but the effectiveness of fecal microbiota transplantation needs long-term observation and further evaluation through large sample data.}, }
@article {pmid29879241, year = {2018}, author = {Meyers, S and Shih, J and Neher, JO and Safranek, S}, title = {Clinical Inquiries: How effective and safe is fecal microbial transplant in preventing C difficile recurrence?.}, journal = {The Journal of family practice}, volume = {67}, number = {6}, pages = {386-388}, pmid = {29879241}, issn = {1533-7294}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/*drug therapy/*prevention &amp; control ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Secondary Prevention/*methods ; Treatment Outcome ; }, abstract = {Fecal microbial transplant (fmt) is reasonably safe and effective. In patients who have had multiple Clostridium difficile infections (CDIs), fecal microbial transplant (FMT) results in a 65% to 80% cure rate with one treatment and 90% to 95% cure rate with repeated treatments compared with a 25% to 27% cure rate for antibiotics (strength of recommendation [SOR]: B, small open-label randomized controlled trials [RCTs]). Fresh and frozen donor feces, administered by either nasogastric tube or colonoscope, produce equal results (SOR B, RCTs). FMT has an overall adverse event rate of 30%, primarily involving abdominal discomfort, but also, rarely, severe infections (0.7%) and death (0.1%) (SOR: B, systematic review not limited to RCTs).}, }
@article {pmid29878420, year = {2018}, author = {Jalanka, J and Hillamaa, A and Arkkila, PE and Satokari, R}, title = {Letter: improvements in mental health after faecal microbiota transplantation-an underexplored treatment-related benefit? Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {47}, number = {11}, pages = {1563-1564}, doi = {10.1111/apt.14668}, pmid = {29878420}, issn = {1365-2036}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases ; Humans ; Mental Health ; }, }
@article {pmid29877649, year = {2018}, author = {Mareschal, J and Schrenzel, J and Lazarevic, V and Genton, L}, title = {[Microbiota and malnutrition: an overview].}, journal = {Revue medicale suisse}, volume = {14}, number = {610}, pages = {1194-1199}, pmid = {29877649}, issn = {1660-9379}, abstract = {Currently, there is an increased interest in the role of gut microbiota in health issues. Evidence shows that an imbalance of gut microbiota or dysbiosis is involved in the mechanisms of weight changes. This review aims at summarizing the present knowledge between gut microbiota and malnutrition. Intestinal bacterial diversity and richness are altered in malnourished people compared to healthy people. The first studies on the modulation of the gut microbiota by probiotics, prebiotics, symbiotics, fecal transplantation and antibiotics for weight gain are encouraging. However, further studies are needed to develop and implement effective treatment for malnutrition.}, }
@article {pmid29877092, year = {2019}, author = {Kang, Y and Cai, Y}, title = {Altered Gut Microbiota in HIV Infection: Future Perspective of Fecal Microbiota Transplantation Therapy.}, journal = {AIDS research and human retroviruses}, volume = {35}, number = {3}, pages = {229-235}, doi = {10.1089/AID.2017.0268}, pmid = {29877092}, issn = {1931-8405}, mesh = {CD4-Positive T-Lymphocytes/immunology ; Disease Progression ; Dysbiosis/immunology ; Fecal Microbiota Transplantation/adverse effects/*trends ; Gastrointestinal Microbiome/genetics/*immunology ; HIV Infections/immunology/*microbiology/*pathology ; HIV-1/immunology ; Humans ; Inflammation/microbiology ; }, abstract = {HIV infection progressively destroys CD4+ mononuclear cells, leading to profound cellular immune deficiency that manifests as life-threatening opportunistic infections and malignancies (i.e., AIDS). Gut microbiota plays key roles in the modulation of host metabolism and gene expression, maintenance of epithelial integrity, and mediation of inflammatory and immunity. Hence, the normal intestinal microbiota plays a major role in the maintenance of health and disease prevention. In fact, a large number of studies have shown that the alteration of the gut microbiota contributes to the pathogenesis of several diseases, such as inflammatory bowel diseases, irritable bowel syndrome, metabolic diseases, anorexia nervosa, autoimmune diseases, multiple sclerosis, cancer, neuropsychiatric disorders, and cardiovascular diseases. Recently, accumulating evidence has shed light on the association of dysbiosis of gut microbiota with HIV infection. Hence, the modification of gut microbiota may be a potential therapeutic tool. Fecal microbiota transplantation may improve the conditions of patients with HIV infection by manipulating the human intestinal bacteria. However, the relevant research is very limited, and a large amount of scientific research work needs to be done in the near future.}, }
@article {pmid29876945, year = {2018}, author = {Mullish, BH}, title = {Letter: improvements in mental health after faecal microbiota transplantation-an underexplored treatment-related benefit?.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {47}, number = {11}, pages = {1562-1563}, pmid = {29876945}, issn = {1365-2036}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; Mental Health ; }, }
@article {pmid29875400, year = {2018}, author = {Harrison, CA and Laubitz, D and Ohland, CL and Midura-Kiela, MT and Patil, K and Besselsen, DG and Jamwal, DR and Jobin, C and Ghishan, FK and Kiela, PR}, title = {Microbial dysbiosis associated with impaired intestinal Na[+]/H[+] exchange accelerates and exacerbates colitis in ex-germ free mice.}, journal = {Mucosal immunology}, volume = {11}, number = {5}, pages = {1329-1341}, pmid = {29875400}, issn = {1935-3456}, support = {R01 DK041274/DK/NIDDK NIH HHS/United States ; R01 DK073338/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteroidaceae/immunology ; Colitis/*metabolism ; Dysbiosis/immunology/*metabolism/microbiology ; Epithelial Cells/immunology/metabolism/microbiology ; Female ; Firmicutes/immunology ; Gastrointestinal Microbiome/*immunology ; Germ-Free Life ; Hydrogen-Ion Concentration ; Immunity/immunology ; Inflammation/immunology/metabolism/microbiology ; Inflammatory Bowel Diseases/immunology/metabolism/microbiology ; Interleukin-10/metabolism ; Intestinal Mucosa/immunology/metabolism/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Sodium-Hydrogen Exchanger 3/metabolism ; Sodium-Hydrogen Exchangers/*metabolism ; }, abstract = {Intestinal epithelial Na[+]/H[+] exchange facilitated by the apical NHE3 (Slc9a3) is a highly regulated process inhibited by intestinal pathogens and in inflammatory bowel diseases. NHE3[-/-] mice develop spontaneous, bacterially mediated colitis, and IBD-like dysbiosis. Disruption of epithelial Na[+]/H[+] exchange in IBD may thus represent a host response contributing to the altered gut microbial ecology, and may play a pivotal role in modulating the severity of inflammation in a microbiome-dependent manner. To test whether microbiome fostered in an NHE3-deficient environment is able to drive mucosal immune responses affecting the onset or severity of colitis, we performed a series of cohousing experiments and fecal microbiome transplants into germ-free Rag-deficient or IL-10[-/-] mice. We determined that in the settings where the microbiome of NHE3-deficient mice was stably engrafted in the recipient host, it was able accelerate the onset and amplify severity of experimental colitis. NHE3-deficiency was characterized by the reduction in pH-sensitive butyrate-producing Firmicutes families Lachnospiraceae and Ruminococcaceae (Clostridia clusters IV and XIVa), with an expansion of inflammation-associated Bacteroidaceae. We conclude that the microbiome fostered by impaired epithelial Na[+]/H[+] exchange enhances the onset and severity of colitis through disruption of the gut microbial ecology.}, }
@article {pmid29874567, year = {2018}, author = {Cignarella, F and Cantoni, C and Ghezzi, L and Salter, A and Dorsett, Y and Chen, L and Phillips, D and Weinstock, GM and Fontana, L and Cross, AH and Zhou, Y and Piccio, L}, title = {Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.}, journal = {Cell metabolism}, volume = {27}, number = {6}, pages = {1222-1235.e6}, pmid = {29874567}, issn = {1932-7420}, support = {C06 RR014513/RR/NCRR NIH HHS/United States ; P30 DK056341/DK/NIDDK NIH HHS/United States ; R01 NS102633/NS/NINDS NIH HHS/United States ; }, mesh = {Adipokines/blood ; Adult ; Animals ; *Autoimmunity ; Bacteroidaceae/metabolism ; Central Nervous System/*immunology ; *Encephalomyelitis, Autoimmune, Experimental/diet therapy/immunology/microbiology ; *Fasting ; Female ; *Gastrointestinal Microbiome ; Humans ; Lactobacillaceae/metabolism ; Mice ; Mice, Inbred C57BL ; Middle Aged ; *Multiple Sclerosis/diet therapy/immunology/microbiology ; Pilot Projects ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; }, abstract = {Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome.}, }
@article {pmid29870851, year = {2018}, author = {Ruppé, E and Martin-Loeches, I and Rouzé, A and Levast, B and Ferry, T and Timsit, JF}, title = {What's new in restoring the gut microbiota in ICU patients? Potential role of faecal microbiota transplantation.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {24}, number = {8}, pages = {803-805}, doi = {10.1016/j.cmi.2018.05.020}, pmid = {29870851}, issn = {1469-0691}, mesh = {Critical Care/methods ; Critical Illness/*therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Intensive Care Units ; }, }
@article {pmid29870676, year = {2018}, author = {Kim, TT and Parajuli, N and Sung, MM and Bairwa, SC and Levasseur, J and Soltys, CM and Wishart, DS and Madsen, K and Schertzer, JD and Dyck, JRB}, title = {Fecal transplant from resveratrol-fed donors improves glycaemia and cardiovascular features of the metabolic syndrome in mice.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {315}, number = {4}, pages = {E511-E519}, doi = {10.1152/ajpendo.00471.2017}, pmid = {29870676}, issn = {1522-1555}, support = {//Canadian Institutes for Health Research/International ; }, mesh = {Animals ; Antioxidants/*pharmacology ; Blood Glucose/drug effects/*metabolism ; Blood Pressure ; Colon/immunology ; Cytokines/immunology ; Diet, High-Fat ; Dietary Sucrose ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Hyperglycemia ; Hypertension ; Inflammation ; Magnetic Resonance Spectroscopy ; Metabolic Syndrome/immunology/*metabolism ; Mice ; Obesity/immunology/*metabolism ; Resveratrol/*pharmacology ; }, abstract = {Oral administration of resveratrol attenuates several symptoms associated with the metabolic syndrome, such as impaired glucose homeostasis and hypertension. Recent work has shown that resveratrol can improve glucose homeostasis in obesity via changes in the gut microbiota. Studies involving fecal microbiome transplants (FMTs) suggest that either live gut microbiota or bacterial-derived metabolites from resveratrol ingestion are responsible for producing the observed benefits in recipients. Herein, we show that obese mice receiving FMTs from healthy resveratrol-fed mice have improved glucose homeostasis within 11 days of the first transplant, and that resveratrol-FMTs is more efficacious than oral supplementation of resveratrol for the same duration. The effects of FMTs from resveratrol-fed mice are also associated with decreased inflammation in the colon of obese recipient mice. Furthermore, we show that sterile fecal filtrates from resveratrol-fed mice are sufficient to improve glucose homeostasis in obese mice, demonstrating that nonliving bacterial, metabolites, or other components within the feces of resveratrol-fed mice are sufficient to reduce intestinal inflammation. These postbiotics may be an integral mechanism by which resveratrol improves hyperglycemia in obesity. Resveratrol-FMTs also reduced the systolic blood pressure of hypertensive mice within 2 wk of the first transplant, indicating that the beneficial effects of resveratrol-FMTs may also assist with improving cardiovascular conditions associated with the metabolic syndrome.}, }
@article {pmid29870270, year = {2019}, author = {Larroya-García, A and Navas-Carrillo, D and Orenes-Piñero, E}, title = {Impact of gut microbiota on neurological diseases: Diet composition and novel treatments.}, journal = {Critical reviews in food science and nutrition}, volume = {59}, number = {19}, pages = {3102-3116}, doi = {10.1080/10408398.2018.1484340}, pmid = {29870270}, issn = {1549-7852}, mesh = {*Diet ; *Gastrointestinal Microbiome ; Humans ; Mental Disorders/*microbiology ; Nervous System Diseases/*microbiology ; Prebiotics ; Probiotics ; }, abstract = {Gut microbiota has significant effects on the structure and function of the enteric and central nervous system including human behaviour and brain regulation. Herein, we analyze the role of this intestinal ecosystem, the effects of dietary changes and the administration of nutritional supplements, such as probiotics, prebiotics, or fecal transplantation in neuropsychiatric disorders. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth delivery and environment. However, diet composition and nutritional status has been repeatedly shown to be one of the most critical modifiable factors of this ecosystem. A comprehensively analysis of the microbiome-intestine-brain axis has been performed, including the impact of intestinal bacteria in alterations in the nervous, immune and endocrine systems and their metabolites. Finally, we discuss the latest literature examining the effects of diet composition, nutritional status and microbiota alterations in several neuropsychiatric disorders, such as autism, anxiety, depression, Alzheimer's disease and anorexia nervosa.}, }
@article {pmid29870114, year = {2018}, author = {Chin-Yee, B and Subramanian, SV and Verma, AA and Laupacis, A and Razak, F}, title = {Emerging Trends in Clinical Research: With Implications for Population Health and Health Policy.}, journal = {The Milbank quarterly}, volume = {96}, number = {2}, pages = {369-401}, pmid = {29870114}, issn = {1468-0009}, mesh = {Clinical Nursing Research/*trends ; Clinical Trials as Topic/*statistics &amp; numerical data ; Forecasting ; Health Equity/*trends ; Health Policy/*trends ; Humans ; Population Health/*statistics &amp; numerical data ; }, abstract = {UNLABELLED: Policy Points: Significant advances in clinical medicine that have broader societal relevance may be less accessible to population health researchers and policymakers because of increased specialization within fields. We describe important recent clinical advances and discuss their broader societal impact. These advances include more expansive strategies for disease prevention, the rise of precision medicine, applications of human microbiome research, and new and highly successful treatments for hepatitis C infection. These recent developments in clinical research raise important issues surrounding health care costs and equitable resource allocation that necessitate an ongoing dialogue among the fields of clinical medicine, population health, and health policy.<br><br>CONTEXT: Developments in clinical medicine have important implications for population health, and there is a need for interdisciplinary engagement among clinical medicine, the social sciences, and public health research. The aim of this article is to help bridge the divide between these fields by exploring major recent advances in clinical medicine that have important implications for population health.<br><br>METHODS: We reviewed the most cited articles published from 2010 to 2015 in 5 high-impact clinical journals and selected 5 randomized controlled trials and 2 related clinical practice guidelines that are broadly relevant to population health and policy.<br><br>FINDINGS: We discuss the following themes: (1) expanding indications for drug therapy and the inherent medicalization of the population as highlighted by studies and clinical guidelines supporting lower blood pressure targets or widespread statin use; (2) the tension in nutritional research between quantifying the impact of isolated nutrients and studying specific foods and dietary patterns, for example, the role of the Mediterranean diet in the primary prevention of cardiovascular disease; (3) the issue of high medication costs and the challenge of providing equitable access raised by the development of new and effective treatments for hepatitis C infection; (4) emerging clinical applications of research on the human microbiome as illustrated by fecal transplant to treat Clostridium difficile infections; and (5) the promise and limitations of precision medicine as demonstrated by the rise of novel targeted therapies in oncology.<br><br>CONCLUSIONS: These developments in clinical science hold promise for improving individual and population health and raise important questions about resource allocation, the role of prevention, and health disparities.}, }
@article {pmid29868248, year = {2018}, author = {Fareed, S and Sarode, N and Stewart, FJ and Malik, A and Laghaie, E and Khizer, S and Yan, F and Pratte, Z and Lewis, J and Immergluck, LC}, title = {Applying fecal microbiota transplantation (FMT) to treat recurrent Clostridium difficile infections (rCDI) in children.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e4663}, pmid = {29868248}, issn = {2167-8359}, support = {K08 HS024338/HS/AHRQ HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal Microbiota Transplantation (FMT) is an innovative means of treating recurrent Clostridium difficile infection (rCDI), through restoration of gut floral balance. However, there is a lack of data concerning the efficacy of FMT and its impact on the gut microbiome among pediatric patients. This study analyzes clinical outcomes and microbial community composition among 15 pediatric patients treated for rCDI via FMT.<br><br>METHODS: This is a prospective, observational, pilot study of 15 children &#x2264;18 years, who presented for rCDI and who met inclusion criteria for FMT at a pediatric hospital and pediatric gastroenterology clinic. Past medical history and demographics were recorded at enrollment and subsequent follow-up. Specimens of the donors' and the patients' pre-FMT and post-FMT fecal specimen were collected and used to assess microbiome composition via 16S rRNA gene sequencing.<br><br>RESULTS: FMT successfully prevented rCDI episodes for minimum of 3 months post-FMT in all patients, with no major adverse effects. Three patients reported continued GI bleeding; however, all three also had underlying Inflammatory Bowel Disease (IBD). Our analyses confirm a significant difference between pre-and post-FMT gut microbiome profiles (Shannon diversity index), whereas no significant difference was observed between post-FMT and donor microbiome profiles. At the phyla level, post-FMT profiles showed significantly increased levels of Bacteroidetes and significantly decreased levels of Proteobacteria. Subjects with underlying IBD showed no difference in their pre-and post-FMT profiles.<br><br>CONCLUSION: The low rate of recurrence or re-infection by C. difficile, coupled with minimal adverse effects post-FMT, suggests that FMT is a viable therapeutic means to treat pediatric rCDI. Post-FMT microbiomes are different from pre-FMT microbiomes, and similar to those of healthy donors, suggesting successful establishment of a healthier microbiome.}, }
@article {pmid29863140, year = {2017}, author = {Konishi, T and Ishida, H and Ueno, H and Kobayashi, H and Hinoi, T and Inoue, Y and Ishida, F and Kanemitsu, Y and Yamaguchi, T and Tomita, N and Matsubara, N and Watanabe, T and Sugihara, K}, title = {Postoperative complications after stapled and hand-sewn ileal pouch-anal anastomosis for familial adenomatous polyposis: A multicenter study.}, journal = {Annals of gastroenterological surgery}, volume = {1}, number = {2}, pages = {143-149}, pmid = {29863140}, issn = {2475-0328}, abstract = {Ileal pouch-anal anastomosis (IPAA) after total proctocolectomy (TPC) can be conducted with either hand-sewn or stapled anastomosis for patients with familial adenomatous polyposis (FAP). Although stapled IPAA without mucosectomy has a higher risk for developing adenomas in the remnant mucosa, it is the simpler procedure with potential benefit in short-term outcomes. However, it remains controversial as to whether stapled IPAA has any advantages in reducing postoperative complications. The aim of the present study was to compare the postoperative complications and short-term outcomes of stapled and hand-sewn IPAA for patients with FAP, using a multicenter cohort sample in Japan. Data of 143 patients with FAP who underwent TPC with stapled IPAA (n=37) and hand-sewn IPAA (n=106) at 23 institutions between 2000 and 2012 were collected. Postoperative complications, proportion of ostomy, fecal continence and overall survival were compared. Overall rates of the Clavien-Dindo grade II-IV complications were not different between the two groups (19% in stapled vs 25% in hand-sewn, P=.42), with significantly fewer pouch-related complications including leakage, pelvic abscess, vaginal fistula and anastomotic stricture in stapled IPAA (none in stapled vs 11% in hand-sewn, P=.036). There was no mortality. Proportion of ostomy at 12 months was similar (2.7% in stapled vs 4.3% in hand-sewn, P=.26). Mean Wexner score was similar. (0.47 in stapled vs 2.0 in hand-sewn, P=.12). Five-year overall survival excluding Stage IV patients was 96% in both groups. Stapled IPAA is a safe option in patients with FAP with a potential benefit in reducing pouch-related complications.}, }
@article {pmid29860912, year = {2018}, author = {Juul, FE and Garborg, K and Bretthauer, M and Skudal, H and Øines, MN and Wiig, H and Rose, &#xd8; and Seip, B and Lamont, JT and Midtvedt, T and Valeur, J and Kalager, M and Holme, &#xd8; and Helsingen, L and Løberg, M and Adami, HO}, title = {Fecal Microbiota Transplantation for Primary Clostridium difficile Infection.}, journal = {The New England journal of medicine}, volume = {378}, number = {26}, pages = {2535-2536}, doi = {10.1056/NEJMc1803103}, pmid = {29860912}, issn = {1533-4406}, mesh = {Anti-Infective Agents/*therapeutic use ; Clostridioides difficile ; Clostridium Infections/drug therapy/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Metronidazole/*therapeutic use ; Recurrence ; Treatment Outcome ; }, }
@article {pmid29859984, year = {2019}, author = {Pringle, PL and Soto, MT and Chung, RT and Hohmann, E}, title = {Patients With Cirrhosis Require More Fecal Microbiota Capsules to Cure Refractory and Recurrent Clostridium difficile Infections.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {4}, pages = {791-793}, doi = {10.1016/j.cgh.2018.05.038}, pmid = {29859984}, issn = {1542-7714}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Capsules/administration &amp; dosage ; Child ; Clostridium Infections/*prevention &amp; control ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Liver Cirrhosis/*complications ; Male ; Middle Aged ; Prospective Studies ; *Secondary Prevention ; Treatment Outcome ; Young Adult ; }, abstract = {The incidence of recurrent and refractory Clostridium difficile (rCDI) is increasing.[1] Cirrhotic patients are at increased risk of CDI as a result of frequent hospitalizations, prophylactic antibiotics, proton pump inhibitor use, and comorbidities.[2] In addition, cirrhotic patients with CDI have a higher mortality rate, longer length of stay, and a higher cost compared with noncirrhotic patients.[3].}, }
@article {pmid29858434, year = {2018}, author = {Mullish, BH and Williams, HR}, title = {Clostridium difficile infection and antibiotic-associated diarrhoea.}, journal = {Clinical medicine (London, England)}, volume = {18}, number = {3}, pages = {237-241}, pmid = {29858434}, issn = {1473-4893}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Anti-Bacterial Agents/adverse effects/*therapeutic use ; Clostridioides difficile ; Clostridium Infections/chemically induced/diagnosis/therapy ; Diarrhea/chemically induced/diagnosis/*therapy ; Enterocolitis, Pseudomembranous/chemically induced/diagnosis/*therapy ; *Fecal Microbiota Transplantation ; Fidaxomicin/therapeutic use ; Humans ; Metronidazole/therapeutic use ; Probiotics/*therapeutic use ; Vancomycin/therapeutic use ; }, abstract = {Antibiotic-associated diarrhoea is among the most common adverse events related to antibiotic use. Most cases are mild, but Clostridium difficile infection causes a spectrum of disease, ranging from occasional diarrhoea to colitis, toxic megacolon, and potentially death. Recent developments in our understanding of the biology of the gut microbiota have provided new insights into the pathogenesis of these conditions, and have revealed a role for manipulation of the gut microbiota as a novel therapeutic approach. This review will give an overview of the assessment of these conditions, before focusing on the rapidly developing area of their treatment.}, }
@article {pmid29851248, year = {2018}, author = {Toral, M and Romero, M and Rodríguez-Nogales, A and Jiménez, R and Robles-Vera, I and Algieri, F and Chueca-Porcuna, N and Sánchez, M and de la Visitación, N and Olivares, M and García, F and Pérez-Vizcaíno, F and Gálvez, J and Duarte, J}, title = {Lactobacillus fermentum Improves Tacrolimus-Induced Hypertension by Restoring Vascular Redox State and Improving eNOS Coupling.}, journal = {Molecular nutrition &amp; food research}, volume = {62}, number = {14}, pages = {e1800033}, doi = {10.1002/mnfr.201800033}, pmid = {29851248}, issn = {1613-4133}, support = {SAF2014-55523-R//Comisi&#xf3;n Interministerial de Ciencia y Tecnolog&#xed;a, Ministerio de Econom&#xed;a y competitividad/ ; SAF2014-55399-R//Comisi&#xf3;n Interministerial de Ciencia y Tecnolog&#xed;a, Ministerio de Econom&#xed;a y competitividad/ ; SAF2010-22066-C02-01//Comisi&#xf3;n Interministerial de Ciencia y Tecnolog&#xed;a, Ministerio de Econom&#xed;a y competitividad/ ; -02//Comisi&#xf3;n Interministerial de Ciencia y Tecnolog&#xed;a, Ministerio de Econom&#xed;a y competitividad/ ; AGL2015-67995-C3-3-R//Comisi&#xf3;n Interministerial de Ciencia y Tecnolog&#xed;a, Ministerio de Econom&#xed;a y competitividad/ ; P12-CTS-2722//Junta de Andaluc&#xed;a/ ; AGR-6826//Junta de Andaluc&#xed;a/ ; CTS 164//Junta de Andaluc&#xed;a/ ; RIC//Ministerio de Economia y Competitividad, Instituto de Salud Carlos III/ ; RD12/0042/0011//Ministerio de Economia y Competitividad, Instituto de Salud Carlos III/ ; CIBER-ehd//Ministerio de Economia y Competitividad, Instituto de Salud Carlos III/ ; CIBER-CV//Ministerio de Economia y Competitividad, Instituto de Salud Carlos III/ ; }, abstract = {SCOPE: The aim is to analyze whether the probiotic Lactobacillus fermentum CECT5716 (LC40) can prevent endothelial dysfunction and hypertension induced by tacrolimus in mice.<br><br>METHODS AND RESULTS: Tacrolimus increases systolic blood pressure (SBP) and impairs endothelium-dependent relaxation to acetylcholine and these effects are partially prevented by LC40. Endothelial dysfunction induced by tacrolimus is related to both increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) and uncoupled endothelial nitric oxide synthase (eNOS)-driven superoxide production and Rho-kinase-mediated eNOS inhibition. LC40 treatment prevents all the aortic changes induced by tacrolimus. LC40 restores the imbalance between T-helper 17 (Th17)/regulatory T (Treg) cells induced by tacrolimus in mesenteric lymph nodes and the spleen. Tacrolimus-induced gut dysbiosis, that is, it decreases microbial diversity, increases the Firmicutes/Bacteroidetes (F/B) ratio and decreases acetate- and butyrate-producing bacteria, and these effects are prevented by LC40. Fecal microbiota transplantation (FMT) from LC40-treated mice to control mice prevents the increase in SBP and the impaired relaxation to acetylcholine induced by tacrolimus.<br><br>CONCLUSION: LC40 treatment prevents hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects are associated with a reduction in vascular oxidative stress, mainly through NOX2 downregulation and prevention of eNOS uncoupling, and inflammation possibly because of decreased Th17 and increased Treg cells polarization in mesenteric lymph nodes.}, }
@article {pmid29851107, year = {2018}, author = {Ianiro, G and Masucci, L and Quaranta, G and Simonelli, C and Lopetuso, LR and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Randomised clinical trial: faecal microbiota transplantation by colonoscopy plus vancomycin for the treatment of severe refractory Clostridium difficile infection-single versus multiple infusions.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {48}, number = {2}, pages = {152-159}, doi = {10.1111/apt.14816}, pmid = {29851107}, issn = {1365-2036}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/drug effects ; Clostridium Infections/microbiology/*therapy ; Colonoscopy/*methods ; Combined Modality Therapy ; *Drug Resistance, Bacterial ; Enterocolitis, Pseudomembranous/microbiology/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Severity of Illness Index ; Treatment Outcome ; Vancomycin/*therapeutic use ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection. Far less evidence exists on the efficacy of FMT in treating severe Clostridium difficile infection refractory to antibiotics.<br><br>AIM: To compare the efficacy of two FMT-based protocols associated with vancomycin in curing subjects with severe Clostridium difficile infection refractory to antibiotics.<br><br>METHODS: Subjects with severe Clostridium difficile infection refractory to antibiotics were randomly assigned to one of the two following treatment arms: (1) FMT-S, including a single faecal infusion via colonoscopy followed by a 14-day vancomycin course, (2) FMT-M, including multiple faecal infusions plus a 14-day vancomycin course. In the FMT-M group, all subjects received at least two infusions, while those with pseudomembranous colitis underwent further infusions until the disappearance of pseudomembranes. The primary outcome was the cure of refractory severe Clostridium difficile infection.<br><br>RESULTS: Fifty six subjects, 28 in each treatment arm, were enrolled. Twenty one patients in the FMT-S group and 28 patients in the FMT-M group were cured (75%&#xa0;vs 100%, respectively, both in per protocol and intention-to-treat analyses; P&#xa0;=&#xa0;0.01). No serious adverse events associated with any of the two treatment protocols were observed.<br><br>CONCLUSIONS: A pseudomembrane-driven FMT protocol consisting of multiple faecal infusions and concomitant vancomycin was significantly more effective than a single faecal transplant followed by vancomycin in curing severe Clostridium difficile infection refractory to antibiotics. Clinical-Trials.gov registration number: NCT03427229.}, }
@article {pmid29849592, year = {2018}, author = {Cao, Y and Zhang, B and Wu, Y and Wang, Q and Wang, J and Shen, F}, title = {The Value of Fecal Microbiota Transplantation in the Treatment of Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis.}, journal = {Gastroenterology research and practice}, volume = {2018}, number = {}, pages = {5480961}, pmid = {29849592}, issn = {1687-6121}, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) has challenged the traditional management of ulcerative colitis (UC) in recent years, while it remained controversial. We aimed to provide a systematic protocol of FMT treatment on UC.<br><br>METHODS: Studies reporting on FMT treatment in UC patients were performed. A fixed-effect model was used to assess the efficacy of FMT.<br><br>RESULTS: Eighteen studies were enrolled (n = 446). A pooled proportion of patients who received FMT had a significant efficacy compared to the placebo group (odds ratio (OR): 2.73, P = 0.002) with a low risk of heterogeneity (P = 0.59, I[2] = 0%). The Mayo score decreased to 5 points in a state of mild-moderate activity after FMT treatment, and the optimal range of the Mayo score baseline was 6-9 for FMT administration. Then, the baseline of the Shannon diversity index (SDI) had a negative correlation with the clinical response rate (R = -0.992, P = 0.08) or remission rate (R = -0.998, P = 0.036), and the optimal diversity of bacteria was at 7 days to one month. Moreover, the colonoscopy delivery and unrelated fecal donor had slight superiorities of FMT treatment.<br><br>CONCLUSION: FMT treatment had a higher efficacy and shorter time-point of early assessment of effectiveness on UC patients compared to traditional therapies. And the optimal FMT delivery and donor were colonoscopy delivery and unrelated donor in clinical practice.}, }
@article {pmid29848602, year = {2018}, author = {Gerber, JS and Berney-Meyer, L and Segerer, S}, title = {Clostridium Ramosum-A Rare Cause of Peritoneal Dialysis-Related Peritonitis.}, journal = {Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis}, volume = {38}, number = {3}, pages = {231-232}, doi = {10.3747/pdi.2017.00153}, pmid = {29848602}, issn = {1718-4304}, mesh = {Aged ; Clostridium/*pathogenicity ; Clostridium Infections/*diagnosis/etiology ; Humans ; Kidney Failure, Chronic/*therapy ; Male ; Peritoneal Dialysis/*adverse effects ; Peritonitis/*diagnosis/*microbiology ; }, abstract = {We present the first report of a patient with peritoneal dialysis (PD)-related peritonitis due to Clostridium ramosum, an anaerobe bacterium that is commonly found in normal fecal flora. On rare occasions, it can be pathogenic in immunocompromised individuals. Clostridium species, including Clostridium ramosum, should be included in the differential diagnosis of PD-related peritonitis.}, }
@article {pmid29846464, year = {2018}, author = {Messias, BA and Franchi, BF and Pontes, PH and Barbosa, D&#xc1;AM and Viana, CAS}, title = {Fecal microbiota transplantation in the treatment of Clostridium difficile infection: state of the art and literature review.}, journal = {Revista do Colegio Brasileiro de Cirurgioes}, volume = {45}, number = {2}, pages = {e1609}, doi = {10.1590/0100-6991e-20181609}, pmid = {29846464}, issn = {1809-4546}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Humans ; }, abstract = {Clostridium difficile infection is a common complication following intestinal dysbiosis caused by abusive antibiotic use. It presents medical importance due to the high rates of recurrence and morbidity. Fecal microbiota transplantation is an effective alternative for the treatment of recurrent and refractory C. difficile infection and consists of introducing the intestinal microbiota from a healthy donor into a patient with this infection. The exact physiological mechanism by which fecal microbiota transplantation alters the intestinal microbiota is not well established, but it is clear that it restores the diversity and structure of the microbiota by promoting increased resistance to colonization by C. difficile. Several routes of transplant administration are being studied and used according to the advantages presented. All forms of application had a high cure rate, and the colonoscopic route was the most used. No relevant complications and adverse events have been documented, and the cost-effectiveness over conventional treatment has proven advantageous. Despite its efficacy, it is not commonly used as initial therapy, and more studies are needed to establish this therapy as the first option in case of refractory and recurrent Clostridium difficileinfection.}, }
@article {pmid29843959, year = {2018}, author = {Adolph, TE and Grander, C and Moschen, AR and Tilg, H}, title = {Liver-Microbiome Axis in Health and Disease.}, journal = {Trends in immunology}, volume = {39}, number = {9}, pages = {712-723}, doi = {10.1016/j.it.2018.05.002}, pmid = {29843959}, issn = {1471-4981}, mesh = {Animals ; *Disease Susceptibility ; Gastrointestinal Microbiome/immunology ; *Homeostasis ; Host-Pathogen Interactions/immunology ; Humans ; Liver/*physiology ; Liver Diseases/etiology/metabolism/pathology ; Liver Regeneration ; *Microbiota/immunology ; }, abstract = {The intestinal and hepatobiliary tract exhibits host-specific commensal colonization. The resident microbiota has emerged as a key player in intestinal and hepatic diseases. Alcoholic and nonalcoholic fatty liver diseases (ALD/NAFLD), primary sclerosing cholangitis (PSC), liver cirrhosis, and some of their clinical complications, such as hepatic encephalopathy (HE), have been linked to a microbial signature, as also observed for severe liver inflammation in alcoholic hepatitis. In turn, the liver impacts, and communicates with, the microbiota through hepatic mediators, such as bile acids or inflammatory signals. Therefore, a liver-microbiome bidirectional crosstalk appears to be critical in health and various liver diseases and could be therapeutically targeted, such as by fecal microbiota transplantation.}, }
@article {pmid29843854, year = {2018}, author = {Lee, S and Drennan, K and Simons, G and Hepple, A and Karlsson, K and Lowman, W and Gaylard, PC and McNamara, L and Fabian, J}, title = {The 'ins and outs' of faecal microbiota transplant for recurrent Clostridium difficile diarrhoea at Wits Donald Gordon Medical Centre, Johannesburg, South Africa.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {108}, number = {5}, pages = {403-407}, doi = {10.7196/SAMJ.2018.v108i5.12367}, pmid = {29843854}, issn = {0256-9574}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/administration &amp; dosage/adverse effects ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/complications/diagnosis/epidemiology/*therapy ; *Cross Infection/epidemiology/microbiology/therapy ; Diarrhea/epidemiology/microbiology/*therapy ; Drug Resistance, Bacterial ; *Fecal Microbiota Transplantation/adverse effects/methods/statistics &amp; numerical data ; Female ; Humans ; Intubation, Gastrointestinal/adverse effects/methods ; Male ; *Metronidazole/administration &amp; dosage/adverse effects ; Middle Aged ; Outcome and Process Assessment, Health Care ; Recurrence ; South Africa/epidemiology ; *Vancomycin/administration &amp; dosage/adverse effects ; }, abstract = {BACKGROUND: Clostridium difficile-associated diarrhoea (CDAD) is a potentially life-threatening condition that is becoming increasingly common. A persistent burden of this infectious illness has been demonstrated over the past 4 years at Wits Donald Gordon Medical Centre (WDGMC), Johannesburg, South Africa, through implementation of active surveillance of hospital-acquired infections as part of the infection prevention and control programme. Oral treatment with metronidazole or vancomycin is recommended, but there is a major problem with symptomatic recurrence after treatment. Replacement of normal flora by the administration of donor stool through colonoscopy or nasogastric/duodenal routes is becoming increasingly popular.<br><br>OBJECTIVES: To identify risk factors for the development of CDAD in patients referred for faecal microbiota transplant (FMT) and evaluate the safety of administration of donor stool as an outpatient procedure, including via the nasogastric route.<br><br>METHODS: A retrospective record review of patients with recurrent CDAD referred for FMT at WDGMC between 1 January 2012 and 31 December 2016 was conducted.<br><br>RESULTS: Twenty-seven patients were identified, all of whom fulfilled the criteria for recurrent CDAD. One-third were aged >65 years, and the majority were female. The most common risk factors were prior exposure to antibiotics or proton-pump inhibitors and underlying inflammatory bowel disease. Three procedures were carried out as inpatients and 24 in the outpatient gastroenterology unit. At 4-week follow-up, all patients reported clinical resolution of their diarrhoea after a single treatment and there were no recurrences. The FMT procedure was associated with no morbidity (with particular reference to the risk of aspiration when administered via the nasogastric route) or mortality.<br><br>CONCLUSIONS: This case series confirms that FMT is a safe and effective therapy for recurrent CDAD. In most cases it can be administered via the nasogastric route in the outpatient department. We propose that the recently published South African Gastroenterology Society guidelines be reviewed with regard to recommendations for the route of administration of FMT and hospital admission. Meticulous prescription practice by clinicians practising in hospitals and outpatient settings, with particular attention to antimicrobials and chronic medication, is urgently required to prevent this debilitating and potentially life-threatening condition.}, }
@article {pmid29842914, year = {2018}, author = {Feghoul, L and Mercier-Delarue, S and Salmona, M and Ntsiba, N and Dalle, JH and Baruchel, A and Klonjkowski, B and Richardson, J and Simon, F and LeGoff, J}, title = {Genetic diversity of the human adenovirus species C DNA polymerase.}, journal = {Antiviral research}, volume = {156}, number = {}, pages = {1-9}, doi = {10.1016/j.antiviral.2018.05.011}, pmid = {29842914}, issn = {1872-9096}, mesh = {Adenovirus Infections, Human/virology ; Adenoviruses, Human/classification/*enzymology/genetics/isolation &amp; purification ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; DNA-Directed DNA Polymerase/*classification/*genetics ; Feces/virology ; Female ; *Genetic Variation ; Genotype ; Hematopoietic Stem Cells ; Humans ; Infant ; Male ; Middle Aged ; Respiratory System/virology ; Young Adult ; }, abstract = {BACKGROUND: Human Adenovirus (HAdV) are responsible for severe infections in hematopoietic stem cells transplant (HSCT) recipient, species C viruses being the most commonly observed in this population. There is no approved antiviral treatment yet. Cidofovir (CDV), a cytidine analog, is the most frequently used and its lipophilic conjugate, brincidofovir (BCV), is under clinical development. These drugs target the viral DNA polymerase (DNA pol). Little is known about the natural polymorphism of HAdV DNA pol in clinical strains.<br><br>METHODS: We assessed the inter- and intra-species variability of the whole gene coding for HAdV DNA pol of HAdV clinical strains of species C. The study included 60 species C HAdV (21 C1, 27 C2 and 12 C5) strains isolated from patients with symptomatic infections who had never experienced CDV or BCV treatments and 20 reference strains. We also evaluated the emergence of mutations in thrirteen patients with persistent HAdV infection despite antiviral treatment.<br><br>RESULTS: We identified 356 polymorphic nucleotide positions (9.9% of the whole gene), including 102 positions with nonsynonymous mutations (28.0%) representing 8.7% of all amino acids. The mean numbers of nucleotide and amino acid mutations per strain were 23.1 (&#xb1;6.2) and 5.2 (&#xb1;2.4) respectively. Most of amino acid substitutions (60.6%) were observed in one instance only. A minority (13.8%) were observed in more than 10% of all strains. The most variable region was the NH2 terminal domain (44.2% of amino acid mutations). Mutations in the exonuclease domain accounted for 27.8%. The binding domains for the terminal protein (TPR), TPR1 and TPR2, presented a limited number of mutations, which were nonetheless frequently observed (62.5% and 58.8% of strains for TPR1 and TPR2, respectively). None of the mutations associated with CDV or BCV resistance were detected. In patients receieving antiviral drugs with persistent HAdV replication, we identified a new mutation in the NH2 terminal region.<br><br>CONCLUSIONS: Our study shows a high diversity in HAdV DNA pol sequences in clinical species C HAdV and provides a comprehensive mapping of its natural polymorphism. These data will contribute to the interpretation of HAdV DNA pol mutations selected in patients receiving antiviral treatments.}, }
@article {pmid29808074, year = {2018}, author = {Majid, A and Jamali, M}, title = {Faecal microbial transplant: Therapy of the past, magic pill of the present?.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {68}, number = {4}, pages = {691}, pmid = {29808074}, issn = {0030-9982}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid29807377, year = {2018}, author = {Lübbert, C and Lippmann, N and von Braun, A}, title = {[New Guidelines and Data to Clostridium difficile - What's New?].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {143}, number = {11}, pages = {787-792}, doi = {10.1055/a-0585-9595}, pmid = {29807377}, issn = {1439-4413}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/epidemiology/therapy ; Fecal Microbiota Transplantation ; Fidaxomicin ; Germany ; Humans ; Practice Guidelines as Topic ; }, abstract = {The incidence of Clostridium difficile infections (CDI) remains on a high level globally. In Germany, the burden of disease and especially the number of severe or even lethal cases continue to increase. The main risk factor for the development of CDI is the exposure to broad-spectrum antibiotics, which disturb the intestinal microbiota and therefore enable the colonization with C. difficile. According to IDSA's and SHEA's updated US guidelines, vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin, but its advantage is the lower rate of recurrence. For the treatment of multiple relapsing CDI, there are assured treatment successes of ≥ 90 % through a fecal microbiome transfer (FMT), whereby FMT in Germany currently only has the status of an individual therapeutic attempt. Thus, an evidence-based general recommendation for clinical practice is not possible. Currently, new antibiotics with narrow-spectrum activity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Furthermore, recent clinical studies demonstrated that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI. However, pivotal clinical trials have so far not been completed.}, }
@article {pmid29804833, year = {2018}, author = {Olson, CA and Vuong, HE and Yano, JM and Liang, QY and Nusbaum, DJ and Hsiao, EY}, title = {The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet.}, journal = {Cell}, volume = {173}, number = {7}, pages = {1728-1741.e13}, pmid = {29804833}, issn = {1097-4172}, support = {F31 MH090749/MH/NIMH NIH HHS/United States ; T32 DK007180/DK/NIDDK NIH HHS/United States ; T32 GM065823/GM/NIGMS NIH HHS/United States ; P30 DK041301/DK/NIDDK NIH HHS/United States ; DP5 OD017924/OD/NIH HHS/United States ; K12 GM106996/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacteroides/drug effects/genetics/isolation &amp; purification ; *Diet, Ketogenic ; Disease Models, Animal ; Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; Glutamic Acid/metabolism ; Hippocampus/metabolism ; Intestinal Mucosa/metabolism ; Kv1.1 Potassium Channel/deficiency/genetics ; Metabolome/drug effects ; Mice ; Mice, Inbred C3H ; Mice, Knockout ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics/metabolism ; Seizures/*diet therapy/pathology ; gamma-Aminobutyric Acid/metabolism ; gamma-Glutamyltransferase/metabolism ; }, abstract = {The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here, we show that the gut microbiota is altered by the KD and required for protection against acute electrically induced seizures and spontaneous tonic-clonic seizures in two mouse models. Mice treated with antibiotics or reared germ free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiotic co-colonization with, KD-associated Akkermansia and Parabacteroides restores seizure protection. Moreover, transplantation of the KD gut microbiota and treatment with Akkermansia and Parabacteroides each confer seizure protection to mice fed a control diet. Alterations in colonic lumenal, serum, and hippocampal metabolomic profiles correlate with seizure protection, including reductions in systemic gamma-glutamylated amino acids and elevated hippocampal GABA/glutamate levels. Bacterial cross-feeding decreases gamma-glutamyltranspeptidase activity, and inhibiting gamma-glutamylation promotes seizure protection in vivo. Overall, this study reveals that the gut microbiota modulates host metabolism and seizure susceptibility in mice.}, }
@article {pmid29804272, year = {2018}, author = {Jeon, SR and Chai, J and Kim, C and Lee, CH}, title = {Current Evidence for the Management of Inflammatory Bowel Diseases Using Fecal Microbiota Transplantation.}, journal = {Current infectious disease reports}, volume = {20}, number = {8}, pages = {21}, pmid = {29804272}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: Fecal microbiota transplantation (FMT) has been investigated as a potential treatment for inflammatory bowel disease (IBD). This review examines current evidence around the efficacy and safety of FMT for patients with IBD.<br><br>RECENT FINDINGS: Randomized controlled trials (RCTs) and meta-analyses have suggested that FMT may facilitate clinical and endoscopic remission in patients with active ulcerative colitis (UC). Although the evidence for FMT in Crohn's disease (CD) is more limited, positive outcomes have been observed in small cohort studies. Most adverse events (AEs) were mild and included transient gastrointestinal symptoms. Serious adverse events (SAEs) did not differ significantly between the FMT and control groups, and a marginal increased rate of IBD flares following FMT was observed. Microbiota analysis following FMT showed increased intestinal bacterial diversity and a shift towards the donor microbial profile in recipients' stools. FMT for patients with IBD is promising as RCTs have shown the benefit of FMT for UC, although the efficacy of FMT for CD is less clear. Further large and well-designed trials are necessary to resolve critical issues such as the donor selection, the ideal route of administration, duration, frequency of FMT, and the long-term sustained efficacy and safety.}, }
@article {pmid29804197, year = {2018}, author = {Heiman, S and Weil, M and Shulman, LM and Simon, AJ and Lev, A and Somech, R and Stauber, T}, title = {Co-appearance of OPV and BCG vaccine-derived complications in two infants with severe combined immunodeficiency.}, journal = {Immunologic research}, volume = {66}, number = {3}, pages = {437-443}, pmid = {29804197}, issn = {1559-0755}, mesh = {BCG Vaccine/*adverse effects/immunology ; Bone Marrow Transplantation/methods ; Feces/virology ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Infant ; Mycobacterium bovis/immunology/isolation &amp; purification ; Poliovirus/immunology ; Poliovirus Vaccine, Oral/*adverse effects/immunology ; Severe Combined Immunodeficiency/*diagnosis/etiology/therapy ; Transplantation, Homologous ; Treatment Outcome ; Vaccines, Attenuated/*adverse effects/immunology ; }, abstract = {Infants with severe combined immunodeficiency (SCID) are at risk of developing severe life-threatening infections if they are inadvertently given attenuated live vaccines. Concomitant appearance of two live vaccine-associated complications in one person is rarely reported. In this study, we present two SCID infants, who received BCG and oral polio vaccines according to their local immunization schedule early in life, before the diagnosis of immunodeficiency was made. Their clinical presentation, extensive immunological workup, genetic tests, and clinical disease course are presented. Both patients developed localized and disseminated infections originating from the BCG vaccine (BCGitis and BCGiosis, respectively) and in addition suffered from diarrhea and chronic fecal secretion of vaccine-derived poliovirus. Alarmingly, in case 2, the poliovirus was a type 2 vaccine-derived poliovirus in which both neurovirulence attenuation sites reverted to the neurovirulent genotype. These cases highlight the importance of early recognition of SCID by neonatal screening or thorough family anamnesis, and the need to further defer the timing of administration of attenuated live vaccines.}, }
@article {pmid29804008, year = {2018}, author = {Petrignani, M and Verhoef, L and de Graaf, M and Richardus, JH and Koopmans, M}, title = {Chronic sequelae and severe complications of norovirus infection: A systematic review of literature.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {105}, number = {}, pages = {1-10}, doi = {10.1016/j.jcv.2018.05.004}, pmid = {29804008}, issn = {1873-5967}, mesh = {Caliciviridae Infections/*complications/epidemiology ; Chronic Disease/epidemiology ; Diarrhea/epidemiology/virology ; Disease Progression ; Feces/virology ; Gastroenteritis/complications/epidemiology/*virology ; Humans ; *Immunocompromised Host ; Seizures/etiology ; Wasting Syndrome/epidemiology/virology ; }, abstract = {Norovirus causes an estimated 18% of all cases of acute gastroenteritis worldwide and is found to be associated with mortality. To create a first overview of severe complications and chronic sequelae of norovirus infections, a systematic review of literature was performed. Of 3928 individual hits, 176 publications remained for data extraction. Study periods varied between 1974 and 2017, though strongly skewed towards the last decade (n = 122, 70%). Countries of studies were worldwide, though Africa, and Carribean, Central and South America were underrepresented. Strong evidence was found for chronic diarrhea in immunocompromised patients, affecting 9%-100% of investigated cohorts. The duration of chronic diarrhea varied from four weeks up to nine years, leading to either wasting, weight loss or failure to thrive in a third of the reported cases (224). Other complications with significant evidence were necrotizing enterocolitis (NEC) in preterm infants associated with norovirus infection (8 papers), and benign infantile convulsions with gastroenteritis (BICG; 19 papers). Studies on norovirus infection and inflammatory bowel disease (IBD) mostly concluded against this association (5 of 7). The remaining papers mentioned a large variety of possible sequelae or complications. Based on the available literature, chronic norovirus diarrhea is the major sequela of norovirus infection in primary immune deficient, oncologic and transplant patients. Norovirus infection - like other gastrointestinal pathogens - can cause a range of sequelae and complications, and should be considered in the differential diagnosis of these manifestations.}, }
@article {pmid29794015, year = {2018}, author = {Kamdar, K and Johnson, AMF and Chac, D and Myers, K and Kulur, V and Truevillian, K and DePaolo, RW}, title = {Innate Recognition of the Microbiota by TLR1 Promotes Epithelial Homeostasis and Prevents Chronic Inflammation.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {201}, number = {1}, pages = {230-242}, pmid = {29794015}, issn = {1550-6606}, support = {R01 DK104908/DK/NIDDK NIH HHS/United States ; R21 CA182595/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/isolation &amp; purification/*metabolism ; Bacterial Adhesion/physiology ; Colon/cytology/immunology/pathology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Inflammation/pathology/*prevention &amp; control ; Intestinal Mucosa/*immunology/microbiology/pathology ; Intestine, Small/microbiology/pathology ; Mice ; Mice, Knockout ; Paneth Cells/*pathology ; Signal Transduction/immunology ; Toll-Like Receptor 1/*immunology ; }, abstract = {There is cross-talk between the intestinal epithelium and the microbiota that functions to maintain a tightly regulated microenvironment and prevent chronic inflammation. This communication is partly mediated through the recognition of bacterial proteins by host-encoded innate receptors, such as TLRs. However, studies examining the role of TLR signaling on colonic homeostasis have given variable and conflicting results. Despite its critical role in mediating immunity during enteric infection of the small intestine, TLR1-mediated recognition of microbiota-derived ligands and their influence on colonic homeostasis has not been well studied. In this study, we demonstrate that defective TLR1 recognition of the microbiome by epithelial cells results in disruption of crypt homeostasis specifically within the secretory cell compartment, including a defect in the mucus layer, ectopic Paneth cells in the colon, and an increase in the number of rapidly dividing cells at the base of the crypt. As a consequence of the perturbed epithelial barrier, we found an increase in mucosal-associated and translocated commensal bacteria and chronic low-grade inflammation characterized by an increase in lineage-negative Sca1[+]Thy1[hi] innate lymphoid-like cells that exacerbate inflammation and worsen outcomes in a model of colonic injury and repair. Our findings demonstrate that sensing of the microbiota by TLR1 may provide key signals that regulate the colonic epithelium, thereby limiting inflammation through the prevention of bacterial attachment to the mucosa and exposure to the underlying immune system.}, }
@article {pmid29793999, year = {2018}, author = {Bidu, C and Escoula, Q and Bellenger, S and Spor, A and Galan, M and Geissler, A and Bouchot, A and Dardevet, D and Morio, B and Cani, PD and Lagrost, L and Narce, M and Bellenger, J}, title = {The Transplantation of ω3 PUFA-Altered Gut Microbiota of fat-1 Mice to Wild-Type Littermates Prevents Obesity and Associated Metabolic Disorders.}, journal = {Diabetes}, volume = {67}, number = {8}, pages = {1512-1523}, doi = {10.2337/db17-1488}, pmid = {29793999}, issn = {1939-327X}, mesh = {Animals ; Cadherins/genetics/metabolism ; Diet, Carbohydrate Loading/adverse effects ; Diet, High-Fat/adverse effects ; Dietary Sucrose/adverse effects ; Dysbiosis/microbiology/physiopathology/therapy ; Endotoxemia/etiology/prevention &amp; control ; Fatty Acids, Omega-3/*metabolism ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Glucose Intolerance/microbiology/pathology/physiopathology/*prevention &amp; control ; *Insulin Resistance ; Intestinal Mucosa/metabolism/microbiology/pathology/physiopathology ; Intestines/microbiology/pathology/physiopathology ; Liver/metabolism/pathology ; Male ; Mice, Transgenic ; Muscle, Skeletal/metabolism ; Non-alcoholic Fatty Liver Disease/microbiology/pathology/physiopathology/*prevention &amp; control ; Obesity/microbiology/pathology/physiopathology/*prevention &amp; control ; Permeability ; Phylogeny ; }, abstract = {Altering the gut microbiome may be beneficial to the host and recently arose as a promising strategy to manage obesity. Here, we investigated the relative contribution of ω3 polyunsaturated fatty acid (PUFA)-mediated alterations in the microbiota to metabolic parameter changes in mice. Four groups were compared: male fat-1 transgenic mice (with constitutive production of ω3 PUFAs) and male wild-type (WT) littermates fed an obesogenic (high fat/high sucrose [HFHS]) or a control diet. Unlike WT mice, HFHS-fed fat-1 mice were protected against obesity, glucose intolerance, and hepatic steatosis. Unlike WT mice, fat-1 mice maintained a normal barrier function, resulting in a significantly lower metabolic endotoxemia. The fat-1 mice displayed greater phylogenic diversity in the cecum, and fecal microbiota transplantation from fat-1 to WT mice was able to reverse weight gain and to normalize glucose tolerance and intestinal permeability. We concluded that the ω3 PUFA-mediated alteration of gut microbiota contributed to the prevention of metabolic syndrome in fat-1 mice. It occurred independently of changes in the PUFA content of host tissues and may represent a promising strategy to prevent metabolic disease and preserve a lean phenotype.}, }
@article {pmid29793539, year = {2018}, author = {McIntosh, CM and Chen, L and Shaiber, A and Eren, AM and Alegre, ML}, title = {Gut microbes contribute to variation in solid organ transplant outcomes in mice.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {96}, pmid = {29793539}, issn = {2049-2618}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 AI115716/AI/NIAID NIH HHS/United States ; T32 EB009412/EB/NIBIB NIH HHS/United States ; T32 HD007009/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Graft Rejection/*microbiology ; Graft Survival/*physiology ; Mice ; Mice, Inbred C57BL ; *Organ Transplantation ; Skin/microbiology ; *Skin Transplantation ; Treatment Outcome ; }, abstract = {BACKGROUND: Solid organ transplant recipients show heterogeneity in the occurrence and timing of acute rejection episodes. Understanding the factors responsible for such variability in patient outcomes may lead to improved diagnostic and therapeutic approaches. Rejection kinetics of transplanted organs mainly depends on the extent of genetic disparities between donor and recipient, but a role for environmental factors is emerging. We have recently shown that major alterations of the microbiota following broad-spectrum antibiotics, or use of germ-free animals, promoted longer skin graft survival in mice. Here, we tested whether spontaneous differences in microbial colonization between genetically similar individuals can contribute to variability in graft rejection kinetics.<br><br>RESULTS: We compared rejection kinetics of minor mismatched skin grafts in C57BL/6 mice from Jackson Laboratory (Jax) and Taconic Farms (Tac), genetically similar animals colonized by different commensal microbes. Female Tac mice rejected skin grafts from vendor-matched males more quickly than Jax mice. We observed prolonged graft survival in Tac mice when they were exposed to Jax mice microbiome through co-housing or fecal microbiota transplantation (FMT) by gastric gavage. In contrast, exposure to Tac mice did not change graft rejection kinetics in Jax mice, suggesting a dominant suppressive effect of Jax microbiota. High-throughput sequencing of 16S rRNA gene amplicons from Jax and Tac mice fecal samples confirmed a convergence of microbiota composition after cohousing or fecal transfer. Our analysis of amplicon data associated members of a single bacterial genus, Alistipes, with prolonged graft survival. Consistent with this finding, members of the genus Alistipes were absent in a separate Tac cohort, in which fecal transfer from Jax mice failed to prolong graft survival.<br><br>CONCLUSIONS: These results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft rejection, and contribute to interpersonal variability in graft outcomes. The association between Alistipes and prolonged skin graft survival in mice suggests that members of this genus might affect host physiology, including at sites distal to the gastrointestinal tract. Overall, these findings allude to a potential therapeutic role for specific gut microbes to promote graft survival through the administration of probiotics, or FMT.}, }
@article {pmid29787456, year = {2018}, author = {}, title = {Fecal Microbial Transplant in Children With Ulcerative Colitis: A Randomized, Double Blinded, Placebo-Controlled Pilot Study: Retraction.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000002038}, pmid = {29787456}, issn = {1536-4801}, }
@article {pmid29781761, year = {2019}, author = {Eliakim-Raz, N and Bishara, J}, title = {Prevention and treatment of Clostridium difficile associated diarrhea by reconstitution of the microbiota.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {15}, number = {6}, pages = {1453-1456}, pmid = {29781761}, issn = {2164-554X}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacterial Toxins/immunology ; Clinical Trials as Topic ; Clostridium Infections/*prevention &amp; control/*therapy ; Diarrhea/microbiology/prevention &amp; control/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Recurrence ; }, abstract = {This review summarizes the latest advances in treating and preventing Clostridium difficile infection (CDI), the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. As customary antibiotic therapies against C. difficile, metronidazole and vancomycin, are broad spectrum, they affect greatly the gut microbiota, which result in very high recurrence rates. Therefore, new strategies are researched intensively. New therapies focus on limiting further destruction of the gut microbiota or restoring the microbiota to its pre-destructed state. These include new antibiotics, such as fidaxomicin, which demonstrates reduced CDI recurrences, among other new drugs, biotherapeutic strategies, mainly fecal microbiota transplantation but also competitive inhibition with non-toxigenic strains of C. difficile, and finally, monoclonal antibodies against C. difficile toxins which offer protection against recurrences.}, }
@article {pmid29780597, year = {2018}, author = {Ding, C and Fan, W and Gu, L and Tian, H and Ge, X and Gong, J and Nie, Y and Li, N}, title = {Outcomes and prognostic factors of fecal microbiota transplantation in patients with slow transit constipation: results from a prospective study with long-term follow-up.}, journal = {Gastroenterology report}, volume = {6}, number = {2}, pages = {101-107}, pmid = {29780597}, issn = {2052-0034}, abstract = {BACKGROUND AND AIM: Gut microbiota may contribute to regulate colonic motility, which is involved in the etiology of constipation. Fecal microbiota transplantation (FMT) has been demonstrated to restore intestinal homeostasis. The aim of this study was to evaluate the clinical outcomes and prognostic factors of FMT for the treatment of slow transit constipation (STC).<br><br>METHODS: Fifty-two patients with STC received standardized FMT and were followed up for 6 months. Bowel habit, colonic transit time, constipation-related symptoms (PAC-SYM score), quality of life (PAC-QOL score), treatment satisfaction scores and adverse events were monitored. The primary efficacy endpoint was the proportion of patients having on average three or more complete spontaneous bowel movements (CSBMs) per week.<br><br>RESULTS: The primary efficacy endpoint was achieved in 50.0%, 38.5% and 32.7% of patients over week intervals 3-4, 9-12 and 21-24, respectively (P&#x2009;<&#x2009;0.01 for all comparisons). Significant improvements were also observed in other bowel movement assessments, colonic transit time, constipation-related symptoms and quality of life; but all improvements diminished at weeks 12 and 24. Incompleteness of evacuation served as the only factor associated with efficacy. No serious treatment-related adverse events were observed.<br><br>CONCLUSION: This study suggested FMT was effective and safe for STC, while a late loss of efficacy was also observed. A lower degree of sensation of incompleteness predicted a better outcome.}, }
@article {pmid29779619, year = {2018}, author = {Hochman, J}, title = {Immunoassay helps limit overdiagnosis of Clostridium difficile infection.}, journal = {The Journal of pediatrics}, volume = {199}, number = {}, pages = {283}, doi = {10.1016/j.jpeds.2018.04.030}, pmid = {29779619}, issn = {1097-6833}, mesh = {Child ; *Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; Immunoassay ; Medical Overuse ; }, }
@article {pmid29776435, year = {2018}, author = {Romano, KA and Dill-McFarland, KA and Kasahara, K and Kerby, RL and Vivas, EI and Amador-Noguez, D and Herd, P and Rey, FE}, title = {Fecal Aliquot Straw Technique (FAST) allows for easy and reproducible subsampling: assessing interpersonal variation in trimethylamine-N-oxide (TMAO) accumulation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {91}, pmid = {29776435}, issn = {2049-2618}, support = {AG041868/NH/NIH HHS/United States ; 2016-67017-24416//National Institute of Food and Agriculture/International ; R01 AG041868/AG/NIA NIH HHS/United States ; NLM5T15LM007359//U.S. National Library of Medicine/International ; T15 LM007359/LM/NLM NIH HHS/United States ; P30 AG017266/AG/NIA NIH HHS/United States ; R01 DK108259/DK/NIDDK NIH HHS/United States ; AG017266//Center for the Demography of Health and Aging/International ; DK108259-01/NH/NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*classification/*genetics/isolation &amp; purification ; Base Sequence ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics ; Humans ; Methylamines/*metabolism ; Mice ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Specimen Handling/*methods ; }, abstract = {BACKGROUND: Convenient, reproducible, and rapid preservation of unique biological specimens is pivotal to their use in microbiome analyses. As an increasing number of human studies incorporate the gut microbiome in their design, there is a high demand for streamlined sample collection and storage methods that are amenable to different settings and experimental needs. While several commercial kits address collection/shipping needs for sequence-based studies, these methods do not preserve samples properly for studies that require viable microbes.<br><br>RESULTS: We describe the Fecal Aliquot Straw Technique (FAST) of fecal sample processing for storage and subsampling. This method uses a straw to collect fecal material from samples recently voided or preserved at low temperature but not frozen (i.e., 4&#xa0;&#xb0;C). Different straw aliquots collected from the same sample yielded highly reproducible communities as disclosed by 16S rRNA gene sequencing; operational taxonomic units that were lost, or gained, between the two aliquots represented very low-abundance taxa (i.e., <&#x2009;0.3% of the community). FAST-processed samples inoculated into germ-free animals resulted in gut communities that retained on average ~&#x2009;80% of the donor's bacterial community. Assessment of choline metabolism and trimethylamine-N-oxide accumulation in transplanted mice suggests large interpersonal variation.<br><br>CONCLUSIONS: Overall, FAST allows for repetitive subsampling without thawing of the specimens and requires minimal supplies and storage space, making it convenient to utilize both in the lab and in the field. FAST has the potential to advance microbiome research through easy, reproducible sample processing.}, }
@article {pmid29774575, year = {2018}, author = {Bajaj, JS and Savidge, T and Kassam, ZA and Hylemon, PB and Gillevet, PM}, title = {Reply.}, journal = {Hepatology (Baltimore, Md.)}, volume = {68}, number = {3}, pages = {1206}, doi = {10.1002/hep.30092}, pmid = {29774575}, issn = {1527-3350}, mesh = {*Anti-Bacterial Agents ; *Fecal Microbiota Transplantation ; Humans ; Liver Cirrhosis ; Microbiota ; }, }
@article {pmid29774567, year = {2018}, author = {Mullish, BH and McDonald, JAK and Thursz, MR and Marchesi, JR}, title = {Antibiotic-Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant.}, journal = {Hepatology (Baltimore, Md.)}, volume = {68}, number = {3}, pages = {1205}, pmid = {29774567}, issn = {1527-3350}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Anti-Bacterial Agents ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis ; Microbiota ; }, }
@article {pmid29773467, year = {2018}, author = {Daliri, EB and Tango, CN and Lee, BH and Oh, DH}, title = {Human microbiome restoration and safety.}, journal = {International journal of medical microbiology : IJMM}, volume = {308}, number = {5}, pages = {487-497}, doi = {10.1016/j.ijmm.2018.05.002}, pmid = {29773467}, issn = {1618-0607}, mesh = {Anti-Bacterial Agents ; Bacteria/classification/isolation &amp; purification ; Diet ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*adverse effects/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Probiotics/*administration &amp; dosage ; }, abstract = {The human gut microbiome consists of many bacteria which are in symbiotic relationship with human beings. The gut microbial metabolism, as well as the microbial-host co-metabolism, has been found to greatly influence health and disease. Factors such as diet, antibiotic use and lifestyle have been associated with alterations in the gut microbial community and may result in several pathological conditions. For this reason, several strategies including fecal microbiota transplant and probiotic administration have been applied and proven to be feasible and effective in restoring the gut microbiota in humans. Yet, safety concerns such as potential health risks that may arise from such interventions and how these strategies are regulated need to be addressed. Also, it will be important to know if these microbiome restoration strategies can have a profound impact on health. This review provides an overview of our current knowledge of the microbiome restoration strategies and safety issues on how these strategies are regulated.}, }
@article {pmid29771163, year = {2018}, author = {Sivananthan, K and Petersen, AM}, title = {Review of Saccharomyces boulardii as a treatment option in IBD.}, journal = {Immunopharmacology and immunotoxicology}, volume = {40}, number = {6}, pages = {465-475}, doi = {10.1080/08923973.2018.1469143}, pmid = {29771163}, issn = {1532-2513}, mesh = {Animals ; Clinical Trials as Topic ; Colitis, Ulcerative/drug therapy/microbiology ; Crohn Disease/drug therapy/microbiology ; Gastrointestinal Microbiome/drug effects ; Humans ; Inflammatory Bowel Diseases/*drug therapy/microbiology ; Probiotics/*therapeutic use ; Saccharomyces boulardii/*growth &amp; development ; }, abstract = {CONTEXT: Review of the yeast Saccharomyces boulardii as a treatment option for the inflammatory bowel diseases (IBD) ulcerative colitis and Crohn's disease.<br><br>OBJECTIVE: IBD is caused by an inappropriate immune response to gut microbiota. Treatment options could therefore be prebiotics, probiotics, antibiotics and/or fecal transplant. In this review, we have looked at the evidence for the yeast S. boulardii as a treatment option.<br><br>MATERIAL AND METHODS: Searches in PubMed and the Cochrane Library with the MeSH words 'Saccharomyces boulardii AND IBD', 'Saccharomyces boulardii AND Inflammatory Bowel Disease', 'Saccharomyces boulardii AND ulcerative colitis' and 'Saccharomyces boulardii AND Crohn's disease' gave total a total of 80 articles. After exclusions because of irrelevance, articles in other languages and some articles that were not available, 16 articles were included in this review.<br><br>RESULTS: Three of the clinical trials showed a positive effect of S. boulardii in IBD patients (two Crohn's disease, one ulcerative colitis), while there was one trial that didn't prove any effect (Crohn's disease). Included Animal trials and cell assays describes different anti-inflammatory mechanisms of S. boulardii supporting a possible effect when treating IBD patients.<br><br>DISCUSSION: The number of studies of S. boulardii as treatment for IBD is limited. Furthermore, the existing trials have small populations and short duration.<br><br>CONCLUSION: We do not have enough evidence to prove the effect of S. boulardii in IBD. Saccharomyces boulardii is, however, a plausible treatment option in the future, but more placebo-controlled clinical studies on both patients with ulcerative colitis and Crohn's disease are needed.}, }
@article {pmid29771153, year = {2018}, author = {Nurminen, N and Lin, J and Grönroos, M and Puhakka, R and Kramna, L and Vari, HK and Viskari, H and Oikarinen, S and Roslund, M and Parajuli, A and Tyni, I and Cinek, O and Laitinen, O and Hyöty, H and Sinkkonen, A}, title = {Nature-derived microbiota exposure as a novel immunomodulatory approach.}, journal = {Future microbiology}, volume = {13}, number = {}, pages = {737-744}, doi = {10.2217/fmb-2017-0286}, pmid = {29771153}, issn = {1746-0921}, mesh = {Adult ; Bacteria/classification/genetics/*isolation &amp; purification ; Biodiversity ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/immunology/*microbiology ; Humans ; *Immunity ; Immunomodulation ; Male ; Middle Aged ; Pilot Projects ; Plants/*microbiology ; Skin/immunology/microbiology ; Soil/chemistry ; *Soil Microbiology ; }, abstract = {AIM: Current attempts to modulate the human microbiota and immune responses are based on probiotics or human-derived bacterial transplants. We investigated microbial modulation by soil and plant-based material.<br><br>MATERIALS &amp; METHODS: We performed a pilot study in which healthy adults were exposed to the varied microbial community of a soil- and plant-based material.<br><br>RESULTS: The method was safe and feasible; exposure was associated with an increase in gut microbial diversity.<br><br>CONCLUSION: If these findings are reproduced in larger studies nature-derived microbial exposure strategies could be further developed for testing their efficacy in the treatment and prevention of immune-mediated diseases.}, }
@article {pmid29770137, year = {2018}, author = {Stanisavljević, S and Dinić, M and Jevtić, B and Đedović, N and Momčilović, M and Đokić, J and Golić, N and Mostarica Stojković, M and Miljković, &#x110;}, title = {Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {942}, pmid = {29770137}, issn = {1664-3224}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Cytokines/metabolism ; Disease Models, Animal ; *Disease Resistance/immunology ; Encephalomyelitis, Autoimmune, Experimental/*etiology/metabolism/therapy ; Fecal Microbiota Transplantation/methods ; Female ; *Gastrointestinal Microbiome/drug effects/immunology ; Lymph Nodes/immunology/metabolism ; Metagenome ; Metagenomics/methods ; Peyer's Patches/immunology/metabolism ; Rats ; }, abstract = {Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.}, }
@article {pmid29765165, year = {2018}, author = {Zavrelova, A and Radocha, J and Pliskova, L and Paterova, P and Vejrazkova, E and Cyrany, J and Gabalec, F and Podhola, M and Zak, P}, title = {Detection of cytomegalovirus DNA in fecal samples in the diagnosis of enterocolitis after allogeneic stem cell transplantation.}, journal = {Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia}, volume = {162}, number = {3}, pages = {227-231}, doi = {10.5507/bp.2018.023}, pmid = {29765165}, issn = {1804-7521}, mesh = {Aged ; Cytomegalovirus/genetics/isolation &amp; purification ; Cytomegalovirus Infections/*diagnosis ; DNA, Viral/isolation &amp; purification ; Enterocolitis/*diagnosis/virology ; Feces/virology ; Female ; Hematologic Neoplasms/therapy ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stem Cell Transplantation/*adverse effects ; Transplantation, Homologous ; }, abstract = {BACKGROUND: Cytomegalovirus enterocolitis is a rare but potentially life threatening complication after allogeneic stem cell transplantation. Its early diagnosis and treatment are essential for a successful outcome.<br><br>OBJECTIVE: To determine the potential benefit of fecal CMV DNA detection in the diagnosis of CMV colitis among stem cell transplant recipients.<br><br>STUDY DESIGN: Biopsies from the lower gastrointestinal tract, taken during 69 episodes of diarrhea, were compared with fecal samples previously examined for CMV DNA in 45 patients after allogeneic stem cell transplantation.<br><br>RESULTS: Six confirmed cases of CMV colitis were observed, with 16 out of 69 (23%) fecal samples proving positive for CMV DNA. Only one positive sample correlated with histologically confirmed CMV colitis, and 15 samples were evaluated as false positive. These results provide a 16.7% sensitivity and 76.2% specificity in the diagnosis of CMV enterocolitis.<br><br>CONCLUSION: The examination of fecal samples for the presence of CMV DNA has very low potential in the diagnosis of CMV enterocolitis after allogeneic stem cell transplantation; therefore, a biopsy of the gastrointestinal mucosa is still warranted for correct diagnosis.}, }
@article {pmid29750050, year = {2018}, author = {Segal, JP and Abbasi, F and Kanagasundaram, C and Hart, A}, title = {Does the Internet promote the unregulated use of fecal microbiota transplantation: a potential public health issue?.}, journal = {Clinical and experimental gastroenterology}, volume = {11}, number = {}, pages = {179-183}, pmid = {29750050}, issn = {1178-7023}, abstract = {INTRODUCTION: The Internet has become an increasingly popular resource for medical information. Fecal microbiota transplantation (FMT) has changed the treatment of Clostridium difficile with cure rates of 81% following one infusion of FMT, further studies have since validated these findings. The Medicines and Health care Products Regulatory Agency has classified FMT as a medicine and hence should be only utilized in strict clinical settings.<br><br>METHODS: We searched Facebook, Twitter, Google, and YouTube using the words "Faecal Microbiota Transplantation" and "FMT". We utilized the first 50 hits on each site. We analyzed the percentage of articles that fell outside regulated medical practice. We searched how many clinics in the UK advertised practice that falls outside suggested guidelines.<br><br>RESULTS: Google, YouTube, and Facebook had a variety of information regarding FMT available. Nine out of 50 (18%) of the top 50 google searches can be considered articles that fall outside regulated practice. YouTube highlighted four videos describing how to self-administer FMT, one of these was for ulcerative colitis. Fourteen percent of the top 50 YouTube videos fall outside regulated practice and 8% of the top 50 Facebook searches fall outside regulated clinical practice. There were two clinics in the UK advertising FMT for uses that fall outside regulated practice.<br><br>CONCLUSION: Clinicians and patients need to be aware of the resources available through social media and the Internet. It should be appreciated that some websites fall outside regulated clinical practice. Private clinics offering FMT need to ensure that they are offering FMT within a regulated framework.}, }
@article {pmid29748817, year = {2018}, author = {Mohajeri, MH and Brummer, RJM and Rastall, RA and Weersma, RK and Harmsen, HJM and Faas, M and Eggersdorfer, M}, title = {The role of the microbiome for human health: from basic science to clinical applications.}, journal = {European journal of nutrition}, volume = {57}, number = {Suppl 1}, pages = {1-14}, pmid = {29748817}, issn = {1436-6215}, mesh = {Brain/physiology ; Clostridium Infections ; Diet ; Fatty Acids, Volatile ; Female ; Fermentation ; Gastrointestinal Microbiome/drug effects/physiology ; *Health Status ; Humans ; Hypersensitivity ; Immunity ; Inflammatory Bowel Diseases ; Intestines/growth &amp; development/microbiology ; Microbiota/*physiology ; Netherlands ; Prebiotics/administration &amp; dosage ; Pregnancy ; Probiotics/administration &amp; dosage ; Signal Transduction ; Vitamins/administration &amp; dosage ; }, abstract = {The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health and disease, the development of the microbiome in early-life and the role of the microbiome on the gut-brain axis. The gut microbiota changes dramatically during pregnancy and intrinsic factors (such as stress), in addition to extrinsic factors (such as diet, and drugs) influence the composition and activity of the gut microbiome throughout life. Microbial metabolites, e.g. short-chain fatty acids affect gut-brain signaling and the immune response. The gut microbiota has a regulatory role on anxiety, mood, cognition and pain which is exerted via the gut-brain axis. Ingestion of prebiotics or probiotics has been used to treat a range of conditions including constipation, allergic reactions and infections in infancy, and IBS. Fecal microbiota transplantation (FMT) highly effective for treating recurrent Clostridium difficile infections. The gut microbiome affects virtually all aspects of human health, but the degree of scientific evidence, the models and technologies and the understanding of mechanisms of action vary considerably from one benefit area to the other. For a clinical practice to be broadly accepted, the mode of action, the therapeutic window, and potential side effects need to thoroughly be investigated. This calls for further coordinated state-of-the art research to better understand and document the human gut microbiome's effects on human health.}, }
@article {pmid29746938, year = {2018}, author = {Kellingray, L and Gall, GL and Defernez, M and Beales, ILP and Franslem-Elumogo, N and Narbad, A}, title = {Microbial taxonomic and metabolic alterations during faecal microbiota transplantation to treat Clostridium difficile infection.}, journal = {The Journal of infection}, volume = {77}, number = {2}, pages = {107-118}, doi = {10.1016/j.jinf.2018.04.012}, pmid = {29746938}, issn = {1532-2742}, support = {BBS/E/F/00042733/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/00044453/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S ; Treatment Outcome ; }, abstract = {OBJECTIVES: This study aimed to examine changes to the microbiota composition and metabolic profiles of seven patients with recurrent Clostridium difficile infection (rCDI), following treatment with faecal microbiota transplant (FMT).<br><br>METHODS: 16S rDNA sequencing and [1]H NMR were performed on faecal samples from the patients (pre-, post-FMT, and follow-up) and the associated donor samples. Sparse partial-least-square analysis was used to identify correlations between the two datasets.<br><br>RESULTS: The patients' microbiota post-FMT tended to shift towards the donor microbiota, specifically through proportional increases of Bacteroides, Blautia, and Ruminococcus, and proportional decreases of Enterococcus, Escherichia, and Klebsiella. However, although cured of infection, one patient, who suffers from chronic alcohol abuse, retained the compositional characteristics of the pre-FMT microbiota. Following FMT, increased levels of short-chain fatty acids, particularly butyrate and acetate, were observed in all patients. Sparse partial-least-square analysis confirmed a positive correlation between butyrate and Bacteroides, Blautia, and Ruminococcus, with a negative correlation between butyrate and Klebsiella and Enterococcus.<br><br>CONCLUSIONS: Clear differences were observed in the microbiota composition and metabolic profiles between donors and rCDI patients, which were largely resolved in patients following FMT. Increased levels of butyrate appear to be a factor associated with resolution of rCDI.}, }
@article {pmid29746874, year = {2018}, author = {Enoch, DA and Santos, R and Phillips, CJ and Micallef, C and Murphy, ME and Aliyu, SH and Massey, D and Brown, NM}, title = {Real-world use of fidaxomicin in a large UK tertiary hospital: how effective is it for treating recurrent disease?.}, journal = {The Journal of hospital infection}, volume = {100}, number = {2}, pages = {142-146}, doi = {10.1016/j.jhin.2018.05.001}, pmid = {29746874}, issn = {1532-2939}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Bacterial Infections/*drug therapy ; Female ; Fidaxomicin/*therapeutic use ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Tertiary Care Centers ; Treatment Outcome ; United Kingdom ; }, abstract = {All courses of fidaxomicin use in the study hospital were reviewed. It was used for first recurrence (six times), second recurrence (eight times) and one case of third recurrence. One patients received fidaxomicin as first-line treatment. Eight patients initially responded to therapy; of these, three patients were asymptomatic at 90 days, three patients remained asymptomatic at 30 days, and two patients had recurrences five and nine days after stopping therapy. Four patients failed to respond; of these, two patients required faecal transplantation and one patient required a colectomy. Two patients deteriorated and two patients died. Fidaxomicin was well tolerated. These findings suggest that the utility of fidaxomicin at this stage of infection is unclear.}, }
@article {pmid29745777, year = {2018}, author = {Hvas, CL and Bendix, M and Dige, A and Dahlerup, JF and Agnholt, J}, title = {Current, experimental, and future treatments in inflammatory bowel disease: a clinical review.}, journal = {Immunopharmacology and immunotoxicology}, volume = {40}, number = {6}, pages = {446-460}, doi = {10.1080/08923973.2018.1469144}, pmid = {29745777}, issn = {1532-2513}, mesh = {Cytokines/antagonists &amp; inhibitors/immunology ; Fecal Microbiota Transplantation ; Humans ; Immunity, Mucosal/drug effects ; Immunotherapy/*methods/trends ; Inflammatory Bowel Diseases/drug therapy/immunology/microbiology/*therapy ; Intestinal Mucosa/*drug effects/immunology/microbiology ; Microbiota/drug effects ; Stem Cell Transplantation ; Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; }, abstract = {Inflammatory bowel diseases (IBDs) may result from dysregulated mucosal immune responses directed toward the resident intestinal microbiota. This review describes the hallmark immunobiology of Crohn's disease and ulcerative colitis as well as therapeutic targets and mechanisms of action for current, experimental, and future treatments in IBD. Conventional therapies include 5-aminosalicylic acid, glucocorticosteroids, thiopurines, and methotrexate. Since 1997, monoclonal antibodies have gained widespread use. These consist of antibodies directed against pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-12, and IL-23, or anti-homing antibodies directed against α4β7 integrin. Emerging oral therapies include modulators of intracellular signal transduction such as Janus kinase inhibitors. Vitamin D may help to regulate innate and adaptive immune responses. Modulation of the intestinal microbiota, using live microorganisms (probiotics), substrates for the colonic microbiota (prebiotics), or fecal microbiota transplantation (FMT), is in development. Dietary supplements are in widespread use, but providing evidence for their benefit is challenging. Stem cell treatment and nervous stimulation are promising future treatments.}, }
@article {pmid29744928, year = {2018}, author = {Chen, YJ and Wu, H and Wu, SD and Lu, N and Wang, YT and Liu, HN and Dong, L and Liu, TT and Shen, XZ}, title = {Parasutterella, in association with irritable bowel syndrome and intestinal chronic inflammation.}, journal = {Journal of gastroenterology and hepatology}, volume = {33}, number = {11}, pages = {1844-1852}, doi = {10.1111/jgh.14281}, pmid = {29744928}, issn = {1440-1746}, support = {81272388//National Natural Science Foundation of China/ ; 81172273//National Natural Science Foundation of China/ ; 81101637//National Natural Science Foundation of China/ ; 81101540//National Natural Science Foundation of China/ ; //Foundation of Shanghai Institute of Liver Diseases/ ; 16YF1401500//Shanghai Sailing Program/ ; 2015ZSQN08//Youth Foundation of Zhongshan Hospital/ ; }, mesh = {Adolescent ; Adult ; Aged ; Animals ; Betaproteobacteria/genetics/isolation &amp; purification/*pathogenicity ; DNA, Bacterial/isolation &amp; purification ; Disease Models, Animal ; Disease Progression ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Humans ; Irritable Bowel Syndrome/*etiology/*microbiology ; Male ; Mice, Inbred C57BL ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Young Adult ; }, abstract = {BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a highly prevalent chronic functional gastrointestinal disorder. Recent studies have showed increasing important role of gut microbiota in the pathophysiological changes of IBS. Our study aims to elaborate the association between intestinal flora with the genesis and the development of IBS.<br><br>METHODS: Illumina high-throughput sequencing technology was applied to investigate microbial communities of IBS patients and healthy donors. Stool specimens from the IBS-D patients were equally premixed and implanted into germ free C57B/6 mice to construct IBS animal model, and the normal group was also transplanted with normal premixed feces. The post-transplant defecation and intra-epithelial lymphocyte counts were evaluated. Microbial communities were also checked by the illumina high-throughput sequencing technology.<br><br>RESULTS: Fifteen genuses significantly different were found expressed in the gut flora of IBS patients, and six genuses showed significantly different abundances between the stool specimens of mice of IBS group and normal group. Among these differences, Parasutterella expression was remarkably different in both screening and validation experiments and also related to chronic intestinal inflammation; therefore, Parasutterella expression is considered in association with the development and progression of IBS.<br><br>CONCLUSION: Parasutterella may be related with the genesis and development of IBS and also associated with chronic intestinal inflammation in IBS patients.}, }
@article {pmid29743833, year = {2018}, author = {Fairhurst, NG and Travis, SPL}, title = {Why is it so difficult to evaluate faecal microbiota transplantation as a treatment for ulcerative colitis?.}, journal = {Intestinal research}, volume = {16}, number = {2}, pages = {209-215}, pmid = {29743833}, issn = {1598-9100}, abstract = {Faecal microbiota transplantation (FMT) has recently re-emerged as a viable therapeutic option for colonic disorders. Its efficacy has been proved in the treatment of Clostridium difficile infection which has encouraged research into the use of FMT for other disorders involving gut dysbiosis, such as ulcerative colitis (UC), a chronic inflammatory disease characterized by relapsing and remitting colonic inflammation. Although the FMT protocol for C. difficile treatment is well established, there are numerous additional factors to consider when applying FMT to treat inflammatory diseases. Various studies have attempted to address these factors but technical inconsistency between reports has resulted in a failure to achieve clinically significant findings. Case reports of FMT in UC have shown favorable outcomes yet demonstrating these effects on a larger scale has proved difficult. The following review aims to explore these issues and to analyze why they may be hindering the progression of FMT therapy in UC.}, }
@article {pmid29743671, year = {2018}, author = {Shepherd, ES and DeLoache, WC and Pruss, KM and Whitaker, WR and Sonnenburg, JL}, title = {An exclusive metabolic niche enables strain engraftment in the gut microbiota.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {434-438}, pmid = {29743671}, issn = {1476-4687}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; R01 DK101674/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteroides/growth &amp; development/isolation &amp; purification/physiology ; Colon/*microbiology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Mice ; Sepharose/analogs &amp; derivatives/metabolism ; }, abstract = {The dense microbial ecosystem in the gut is intimately connected to numerous facets of human biology, and manipulation of the gut microbiota has broad implications for human health. In the absence of profound perturbation, the bacterial strains that reside within an individual are mostly stable over time [1] . By contrast, the fate of exogenous commensal and probiotic strains applied to an established microbiota is variable, generally unpredictable and greatly influenced by the background microbiota[2,3]. Therefore, analysis of the factors that govern strain engraftment and abundance is of critical importance to the emerging field of microbiome reprogramming. Here we generate an exclusive metabolic niche in mice via administration of a marine polysaccharide, porphyran, and an exogenous Bacteroides strain harbouring a rare gene cluster for porphyran utilization. Privileged nutrient access enables reliable engraftment of the exogenous strain at predictable abundances in mice harbouring diverse communities of gut microbes. This targeted dietary support is sufficient to overcome priority exclusion by an isogenic strain [4] , and enables strain replacement. We demonstrate transfer of the 60-kb porphyran utilization locus into a naive strain of Bacteroides, and show finely tuned control of strain abundance in the mouse gut across multiple orders of magnitude by varying porphyran dosage. Finally, we show that this system enables the introduction of a new strain into the colonic crypt ecosystem. These data highlight the influence of nutrient availability in shaping microbiota membership, expand the ability to perform a broad spectrum of investigations in the context of a complex microbiota, and have implications for cell-based therapeutic strategies in the gut.}, }
@article {pmid29743453, year = {2018}, author = {Mizuno, S and Nanki, K and Kanai, T}, title = {[Future perspectives on fecal microbiota transplantation].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {115}, number = {5}, pages = {449-459}, doi = {10.11405/nisshoshi.115.449}, pmid = {29743453}, issn = {0446-6586}, mesh = {Clostridioides difficile ; *Fecal Microbiota Transplantation ; Feces ; }, }
@article {pmid29742710, year = {2018}, author = {Wang, HG and Liu, SP and Ma, TH and Yan, W and Zhou, JF and Shi, YT and Shen, P and Yang, XZ and Wu, SN}, title = {Fecal microbiota transplantation treatment for refractory ulcerative colitis with allergy to 5-aminosalicylic acid: A case report.}, journal = {Medicine}, volume = {97}, number = {19}, pages = {e0675}, pmid = {29742710}, issn = {1536-5964}, mesh = {*Anti-Inflammatory Agents, Non-Steroidal ; Colitis, Ulcerative/*therapy ; *Drug Hypersensitivity ; *Fecal Microbiota Transplantation ; Humans ; Male ; *Mesalamine ; Middle Aged ; Remission Induction ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for ulcerative colitis (UC). Here, we report the first case of a UC patient with allergy to 5-aminosalicylic acid (5-ASA) who underwent FMT and achieved clinical remission.<br><br>CASE PRESENTATION: This patient had a 9-year history of UC and was allergic to 5-ASA. He suffered from gradually aggravated abdominal pain and frequent bloody diarrhea. There was a continuous distribution of superficial erosion and ulceration by colonoscopy. After steroid therapy failed, he underwent FMT. The donated fecal microbes were purified in laboratory and then transplanted into the terminal ileum and right colon of the patient by colonoscopy. During the 9 months' follow-up, FMT has proved its efficacy in inducing and maintaining clinical and endoscopic remission of the patient.<br><br>CONCLUSION: The choice of treatment for refractory UC patients who are allergic to 5-ASA is relatively limited. In our case, we highlight the specific role of FMT for refractory UC with absence of 5-ASA through intestinal microbiota reconstruction.}, }
@article {pmid29742516, year = {2018}, author = {Endres, K and Schäfer, KH}, title = {Influence of Commensal Microbiota on the Enteric Nervous System and Its Role in Neurodegenerative Diseases.}, journal = {Journal of innate immunity}, volume = {10}, number = {3}, pages = {172-180}, pmid = {29742516}, issn = {1662-8128}, mesh = {Alzheimer Disease/microbiology/physiopathology/therapy ; Animals ; Enteric Nervous System/pathology/*physiology/physiopathology ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/microbiology/physiopathology ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Neurodegenerative Diseases/*microbiology/physiopathology/therapy ; Neuroprotective Agents/therapeutic use ; Parkinson Disease/microbiology/physiopathology/therapy ; }, abstract = {When thinking about neurodegenerative diseases, the first symptoms that come to mind are loss of memory and learning capabilities, which all resemble hallmarks of manifestation of such diseases in the central nervous system (CNS). However, the gut comprises the largest nervous system outside the CNS that is autonomously active and in close interplay with its microbiota. Therefore, the enteric nervous system (ENS) might serve as an indicator of degenerative pathomechanisms that also affect the CNS. On the other hand, it might offer an entry point for devastating influences from the microbial community or - conversely - for therapeutic approaches via gut commensals. Within the last years, the ENS and gut microbiota therefore have sparked the interest of researchers of CNS diseases and we here report on recent findings and open questions, especially with regard to Alzheimer and Parkinson diseases.}, }
@article {pmid29738579, year = {2018}, author = {Solbach, P and Chhatwal, P and Woltemate, S and Tacconelli, E and Buhl, M and Gerhard, M and Thoeringer, CK and Vehreschild, MJGT and Jazmati, N and Rupp, J and Manns, MP and Bachmann, O and Suerbaum, S}, title = {BaiCD gene cluster abundance is negatively correlated with Clostridium difficile infection.}, journal = {PloS one}, volume = {13}, number = {5}, pages = {e0196977}, pmid = {29738579}, issn = {1932-6203}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins/*genetics ; Bacterial Toxins ; Bile/microbiology ; Bile Acids and Salts/biosynthesis/*genetics ; Clostridioides difficile/*genetics/pathogenicity ; Clostridium Infections/*genetics/microbiology/transmission ; Diarrhea/*genetics/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Male ; Microbiota/genetics ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is a major cause of hospital-acquired diarrhea. Secondary bile acids were shown to confer resistance to colonization by C. difficile. 7α-dehydroxylation is a key step in transformation of primary to secondary bile acids and required genes have been located in a single bile acid-inducible (bai) operon in C. scindens as well as in C. hiranonis, two Clostridium sp. recently reported to protect against C. difficile colonization.<br><br>AIM: To analyze baiCD gene abundance in C. difficile positive and negative fecal samples.<br><br>MATERIAL &amp; METHODS: A species-specific qPCR for detecting baiCD genes was established. Fecal samples of patients with CDI, asymptomatic toxigenic C. difficile colonization (TCD), non-toxigenic C. difficile colonization (NTCD), of C. difficile negative (NC) patients, and of two patients before and after fecal microbiota transplantation (FMT) for recurrent CDI (rCDI) were tested for the presence of the baiCD genes.<br><br>RESULTS: The prevalence of the baiCD gene cluster was significantly higher in C. difficile negative fecal samples than in samples of patients diagnosed with CDI (72.5% (100/138) vs. 35.9% (23/64; p<0.0001). No differences in baiCD gene cluster prevalence were seen between NC and NTCD or NC and TCD samples. Both rCDI patients were baiCD-negative at baseline, but one of the two patients turned positive after successful FMT from a baiCD-positive donor.<br><br>CONCLUSION: Fecal samples of CDI patients are less frequently baiCD-positive than samples from asymptomatic carriers or C. difficile-negative individuals. Furthermore, we present a case of baiCD positivity observed after successful FMT for rCDI.}, }
@article {pmid29736607, year = {2018}, author = {Hwang, IY and Lee, HL and Huang, JG and Lim, YY and Yew, WS and Lee, YS and Chang, MW}, title = {Engineering microbes for targeted strikes against human pathogens.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {75}, number = {15}, pages = {2719-2733}, pmid = {29736607}, issn = {1420-9071}, support = {NUHSRO/2016/053/SRP/05//National University Health System/ ; DPRT/943/09/14//National University of Singapore (SG)/ ; HDTRA1-13-0037//Defense Threat Reduction Agency (US)/ ; MINDEF//Ministry of Defense of Singapore/ ; RE2016-074//Ministry of Defense of Singapore/ ; }, mesh = {Anti-Infective Agents/metabolism/therapeutic use ; Bacteria/*genetics/metabolism ; Bacteriophages/*genetics/metabolism ; Communicable Diseases/diagnosis/therapy ; Fecal Microbiota Transplantation ; *Genetic Engineering ; Humans ; Microbiota ; Phage Therapy ; Probiotics/therapeutic use ; }, abstract = {Lack of pathogen specificity in antimicrobial therapy causes non-discriminant microbial cell killing that disrupts the microflora present. As a result, potentially helpful microbial cells are killed along with the pathogen, altering the biodiversity and dynamic interactions within the population. Moreover, the unwarranted exposure of antibiotics to microbes increases the likelihood of developing resistance and perpetuates the emergence of multidrug resistance. Synthetic biology offers an alternative solution where specificity can be conferred to reduce the non-specific, non-targeted activity of currently available antibiotics, and instead provides targeted therapy against specific pathogens and minimising collateral damage to the host's inherent microbiota. With a greater understanding of the microbiome and the available genetic engineering tools for microbial cells, it is possible to devise antimicrobial strategies for novel antimicrobial therapy that are able to precisely and selectively remove infectious pathogens. Herein, we review the strategies developed by unlocking some of the natural mechanisms used by the microbes and how these may be utilised in targeted antimicrobial therapy, with the promise of reducing the current global bane of multidrug antimicrobial resistance.}, }
@article {pmid29733457, year = {2018}, author = {Spychala, MS and Venna, VR and Jandzinski, M and Doran, SJ and Durgan, DJ and Ganesh, BP and Ajami, NJ and Putluri, N and Graf, J and Bryan, RM and McCullough, LD}, title = {Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome.}, journal = {Annals of neurology}, volume = {84}, number = {1}, pages = {23-36}, pmid = {29733457}, issn = {1531-8249}, support = {R01 NS094543/NS/NINDS NIH HHS/United States ; R01 NS103592/NS/NINDS NIH HHS/United States ; R21 NS094806/NS/NINDS NIH HHS/United States ; R01 NS080531/NS/NINDS NIH HHS/United States ; RF1 AG058463/AG/NIA NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; }, mesh = {Age Factors ; *Aging ; Animals ; Cytokines/metabolism ; Disease Models, Animal ; Exploratory Behavior ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Inflammation/*microbiology/physiopathology ; Mice ; Mice, Inbred C57BL ; Muscle Strength/physiology ; Neurologic Examination ; RNA, Ribosomal, 16S/metabolism ; Stroke/*microbiology/physiopathology ; }, abstract = {OBJECTIVE: Chronic systemic inflammation contributes to the pathogenesis of many age-related diseases. Although not well understood, alterations in the gut microbiota, or dysbiosis, may be responsible for age-related inflammation.<br><br>METHODS: Using stroke as a disease model, we tested the hypothesis that a youthful microbiota, when established in aged mice, produces positive outcomes following ischemic stroke. Conversely, an aged microbiota, when established in young mice, produces negative outcomes after stroke. Young and aged male mice had either a young or an aged microbiota established by fecal transplant gavage (FTG). Mice were subjected to ischemic stroke (middle cerebral artery occlusion; MCAO) or sham surgery. During the subsequent weeks, mice underwent behavioral testing and fecal samples were collected for 16S ribosomal RNA analysis of bacterial content.<br><br>RESULTS: We found that the microbiota is altered after experimental stroke in young mice and resembles the biome of uninjured aged mice. In aged mice, the ratio of Firmicutes to Bacteroidetes (F:B), two main bacterial phyla in gut microbiota, increased &#x223c;9-fold (p&#x2009;<&#x2009;0.001) compared to young. This increased F:B ratio in aged mice is indicative of dysbiosis. Altering the microbiota in young by fecal gavage to resemble that of aged mice (&#x223c;6-fold increase in F:B ratio, p&#x2009;<&#x2009;0.001) increased mortality following MCAO, decreased performance in behavioral testing, and increased cytokine levels. Conversely, altering the microbiota in aged to resemble that of young (&#x223c;9-fold decrease in F:B ratio, p&#x2009;<&#x2009;0.001) increased survival and improved recovery following MCAO.<br><br>INTERPRETATION: Aged biome increased the levels of systemic proinflammatory cytokines. We conclude that the gut microbiota can be modified to positively impact outcomes from age-related diseases. Ann Neurol 2018;83:23-36.}, }
@article {pmid29732995, year = {2018}, author = {de Moreno de LeBlanc, A and Levit, R and de Giori, GS and LeBlanc, JG}, title = {Vitamin Producing Lactic Acid Bacteria as Complementary Treatments for Intestinal Inflammation.}, journal = {Anti-inflammatory &amp; anti-allergy agents in medicinal chemistry}, volume = {17}, number = {1}, pages = {50-56}, doi = {10.2174/1871523017666180502170659}, pmid = {29732995}, issn = {1875-614X}, mesh = {Animals ; Complementary Therapies ; Humans ; Inflammation/therapy ; Inflammatory Bowel Diseases/*therapy ; Lactobacillales/*metabolism ; Probiotics/*therapeutic use ; Vitamins/*metabolism ; }, abstract = {BACKGROUND: Current therapies for against inflammatory bowel disease (IBD) are sometimes limited by high costs, high toxicities and/or undesirable side effects, reasons for which new treatments are constantly being developed and studied. In this regards, an increasing mass of data has demonstrated that fecal transplantations and probiotic supplementations have shown promising effects and could be considered as adjunct IBD treatments to decrease some of the unwanted side effects caused by primary treatments. Furthermore, there is also mounting evidence that suggests that certain vitamins could provide antiinflammatory effects and it has been shown that certain strains of lactic acid bacteria (LAB), the most commonly used probiotic microorganisms, can produce biologically active forms of certain vitamins.<br><br>OBJECTIVE: To discuss the potential role of the vitamin-producing LAB on intestinal inflammatory diseases.<br><br>METHOD: A thorough search of bibliographic databases for peer-reviewed research on the effect of vitamins produced by LAB on inflammatory processes was performed.<br><br>RESULTS: There is mounting research that vitamin producing LAB could provide antiinflammatory effects.<br><br>CONCLUSION: The potential role of vitamin producing LAB was discussed not only because they could be used to decrease inflammation but also because they could provide the host with essential nutrients that are normally deficient in IBD patients due to altered intestinal morphologies.}, }
@article {pmid29728643, year = {2018}, author = {Couturier-Maillard, A and Froux, N and Piotet-Morin, J and Michaudel, C and Brault, L and Le Bérichel, J and Sénéchal, A and Robinet, P and Chenuet, P and Jejou, S and Dumoutier, L and Renauld, JC and Iovanna, J and Huber, S and Chamaillard, M and Quesniaux, V and Sokol, H and Chamaillard, M and Ryffel, B}, title = {Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.}, journal = {Mucosal immunology}, volume = {11}, number = {4}, pages = {1181-1190}, doi = {10.1038/s41385-018-0005-8}, pmid = {29728643}, issn = {1935-3456}, mesh = {Animals ; Cells, Cultured ; Disease Progression ; Gastrointestinal Microbiome/*immunology ; Inflammation/*immunology ; Interleukins/genetics/*metabolism ; Intestines/*immunology/parasitology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pancreatitis-Associated Proteins/genetics/metabolism ; Parasite Load ; Receptors, Interleukin/genetics/metabolism ; Toxoplasma/*physiology ; Toxoplasmosis/*immunology ; Interleukin-22 ; }, abstract = {Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22[-/-] or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.}, }
@article {pmid29728388, year = {2018}, author = {Yan, ZX and Gao, XJ and Li, T and Wei, B and Wang, PP and Yang, Y and Yan, R}, title = {Fecal Microbiota Transplantation in Experimental Ulcerative Colitis Reveals Associated Gut Microbial and Host Metabolic Reprogramming.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {14}, pages = {}, pmid = {29728388}, issn = {1098-5336}, mesh = {Animals ; Colitis, Ulcerative/microbiology/*therapy ; Dextran Sulfate/metabolism ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Male ; Metabolomics ; Pilot Projects ; RNA, Ribosomal, 16S ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Fecal microbiota transplantation (FMT) is gaining attention for the treatment of ulcerative colitis (UC). Data from individual case studies have suggested that FMT may be beneficial for UC, but the detailed microbial and molecular basis remains unknown. Here, we employ 16S rRNA gene sequencing and metabolomics to investigate the influence of FMT on gut microbial community composition and host metabolism in the dextran sulfate sodium-induced UC rat model. The findings from this pilot study suggest that FMT from normal donors to UC recipients could alleviate UC symptoms without close resemblance of donor's gut microbial and metabolic pattern. Meanwhile, FMT from UC donors to normal recipient rats triggered UC symptoms, UC-prone microbial shift, and host metabolic adaption. Gut microbiota under normal conditions could maintain stable species richness and diversity upon FMT intervention, but the disturbed gut microbiota under UC conditions could not maintain such homeostasis. Significant correlations between altered bacterial composition and host metabolism could be assigned to the pathological effects of UC (accounting for 8.0 to 16.2% of total variance) and/or the FMT intervention effects (3.9 to 7.0% of total variance). Overall, our study reveals diverse gut microbial shifts in UC related FMT and their association with host metabolic reprogramming.IMPORTANCE This study combined clinical symptoms measurement, 16S rRNA gene microbial profiling and metabolomics to comprehensively investigate the gut bacterial and host metabolic association and reprogramming in FMT-treated experimental UC. These data can advance our understanding of the effect of FMT on UC and the involvement of gut microbial dysbiosis in the development of UC.}, }
@article {pmid29718144, year = {2018}, author = {Macesic, N and Gomez-Simmonds, A and Sullivan, SB and Giddins, MJ and Ferguson, SA and Korakavi, G and Leeds, D and Park, S and Shim, K and Sowash, MG and Hofbauer, M and Finkel, R and Hu, Y and West, J and Toussaint, NC and Greendyke, WG and Miko, BA and Pereira, MR and Whittier, S and Verna, EC and Uhlemann, AC}, title = {Genomic Surveillance Reveals Diversity of Multidrug-Resistant Organism Colonization and Infection: A Prospective Cohort Study in Liver Transplant Recipients.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {67}, number = {6}, pages = {905-912}, pmid = {29718144}, issn = {1537-6591}, support = {R01 AI116939/AI/NIAID NIH HHS/United States ; T32 AI100852/AI/NIAID NIH HHS/United States ; }, mesh = {Aged ; Bacteria/drug effects/*genetics/isolation &amp; purification ; Carbapenem-Resistant Enterobacteriaceae/drug effects/genetics/isolation &amp; purification ; Carrier State/*microbiology ; Cross Infection ; *Drug Resistance, Multiple, Bacterial ; Feces/microbiology ; Female ; *Genetic Variation ; Genomics ; Humans ; *Liver Transplantation ; Male ; Methicillin-Resistant Staphylococcus aureus/drug effects/genetics/isolation &amp; purification ; Middle Aged ; Prospective Studies ; Sentinel Surveillance ; Transplant Recipients ; Vancomycin-Resistant Enterococci/drug effects/genetics/isolation &amp; purification ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Multidrug-resistant organisms (MDROs) are an important cause of morbidity and mortality after solid organ transplantation. We aimed to characterize MDRO colonization dynamics and infection in liver transplant (LT) recipients through innovative use of active surveillance and whole-genome sequencing (WGS).<br><br>METHODS: We prospectively enrolled consecutive adult patients undergoing LT from March 2014 to March 2016. Fecal samples were collected at multiple timepoints from time of enrollment to 12 months posttransplant. Samples were screened for carbapenem-resistant Enterobacteriaceae (CRE), Enterobacteriaceae resistant to third-generation cephalosporins (Ceph-RE), and vancomycin-resistant enterococci. We performed WGS of CRE and selected Ceph-RE isolates. We also collected clinical data including demographics, transplant characteristics, and infection data.<br><br>RESULTS: We collected 998 stool samples and 119 rectal swabs from 128 patients. MDRO colonization was detected in 86 (67%) patients at least once and was significantly associated with subsequent MDRO infection (0 vs 19.8%, P = .002). Child-Turcotte-Pugh score at LT and duration of post-LT hospitalization were independent predictors of both MDRO colonization and infection. Temporal dynamics differed between MDROs with respect to onset of colonization, clearance, and infections. We detected an unexpected diversity of CRE colonizing isolates and previously unrecognized transmission that spanned Ceph-RE and CRE phenotypes, as well as a cluster of mcr-1-producing isolates.<br><br>CONCLUSIONS: Active surveillance and WGS showed that MDRO colonization is a highly dynamic and complex process after LT. Understanding that complexity is crucial for informing decisions regarding MDRO infection control, use of therapeutic decolonization, and empiric treatment regimens.}, }
@article {pmid29717179, year = {2018}, author = {Wrzosek, L and Ciocan, D and Borentain, P and Spatz, M and Puchois, V and Hugot, C and Ferrere, G and Mayeur, C and Perlemuter, G and Cassard, AM}, title = {Transplantation of human microbiota into conventional mice durably reshapes the gut microbiota.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {6854}, pmid = {29717179}, issn = {2045-2322}, mesh = {Animals ; Bacteroidetes/*growth &amp; development ; Faecalibacterium/*growth &amp; development ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Mice ; Mice, Inbred C57BL ; Polyethylene Glycols/chemistry ; }, abstract = {Human microbiota-associated (HMA) mice are an important model to study the relationship between liver diseases and intestinal microbiota. We describe a new method to humanize conventional mice based on bowel cleansing with polyethylene glycol followed by fecal microbiota transplantation (FMT) from a human donor. Four successive bowel cleansings were sufficient to empty the intestine and decrease the microbiota by 90%. We then compared four different strategies based on the frequency of FMT over four weeks: (1) twice a week; (2) once a week; (3) two FMTs; (4) one FMT. We were able to transfer human bacteria to mice, irrespective of the strategy used. We detected human bacteria after four weeks, even if only one FMT was performed, but there was a shift of the microbiota over time. FMT twice a week for four weeks was too frequent and perturbed the stability of the newly formed ecosystem. FMT once a week appears to be the best compromise as it allowed engraftment of Faecalibacterium, and a higher diversity of bacteria belonging to the Bacteroidales order. Our easy to establish HMA mouse model could be used as an alternative to classical HMA mice to study the relationship between the liver and the microbiota.}, }
@article {pmid29716597, year = {2018}, author = {Leblebicioglu, H and Ozaras, R}, title = {Hepatitis E virus infection in Turkey: a systematic review.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {17}, number = {1}, pages = {17}, pmid = {29716597}, issn = {1476-0711}, mesh = {Adult ; Agricultural Workers' Diseases/virology ; Child, Preschool ; Databases, Factual ; Hepatitis E/*epidemiology/transmission/*virology ; Hepatitis E virus/*pathogenicity ; Hepatitis, Chronic/epidemiology ; Humans ; Kidney Failure, Chronic/epidemiology/virology ; Pregnant People ; Prevalence ; Seroepidemiologic Studies ; Socioeconomic Factors ; Transients and Migrants ; Travel ; Turkey/epidemiology ; }, abstract = {Hepatitis E virus (HEV), a non-enveloped single stranded RNA virus causes sporadic cases of hepatitis or outbreaks. The disease is generally self-limited although it may cause fulminant hepatitis in pregnant women, elderly, those with underlying chronic hepatitis, immunosuppressed, and transplant recipients. It is transmitted through fecal-oral route and zoonotic transmission. Hepatitis is a main health care problem in Turkey; HBV and HCV prevalences are 4 and 1% respectively. Hepatitis D represents another considerable hepatitis etiology with a prevalence of 5-27%. The information about HEV is not clear. In this systematic review, we aimed to analyze HEV studies reported from Turkey, to determine the current situation of the disease in the country, to delineate the limits of the studies and to determine the future study areas. The prevalence of HEV ranged from 0 to 12.4%. Children had lower prevalence than the adults. The prevalence was determined as 7-8% in pregnant women, 13% in chronic HBV patients, 54% in chronic HCV patients, 13.9-20.6% in patients with chronic renal failure, and ≈ 35% in agriculture workers. Among individuals immigrating form Turkey to Europe, HEV seroprevalence was found 10.3% in Italy and 33.4% in the Netherlands. HEV prevalence seems high in certain risk groups. Although previous studies suggest that Turkey is among the endemic countries of HEV, there are some pitfalls for the analysis of data: the studies are not powered enough to represent the whole population; they did not include immunosuppressed patients and solid organ recipients; and the prevalence of non-A non-B hepatitis was not determined.}, }
@article {pmid29714163, year = {2018}, author = {Stillwaggon, E and Perez-Zetune, V and Bialek, SR and Montgomery, SP}, title = {Congenital Chagas Disease in the United States: Cost Savings through Maternal Screening.}, journal = {The American journal of tropical medicine and hygiene}, volume = {98}, number = {6}, pages = {1733-1742}, pmid = {29714163}, issn = {1476-1645}, mesh = {Chagas Disease/*epidemiology/mortality/parasitology/transmission ; Cohort Studies ; Cost Savings ; Diagnostic Tests, Routine ; Female ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical/*prevention &amp; control ; Mass Screening/economics ; Morbidity ; Mothers ; Neonatal Screening/economics ; Pregnancy ; Pregnancy Complications, Parasitic/*epidemiology/mortality/parasitology ; Prevalence ; Trypanosoma cruzi/*isolation &amp; purification ; United States ; }, abstract = {Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors through transfusions, transplants, insect feces in food, and from mother to child during gestation. Congenital infection could perpetuate Chagas disease indefinitely, even in countries without vector transmission. An estimated 30% of infected persons will develop lifelong, potentially fatal, cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment of Chagas disease in the United States. We constructed a decision-analytic model to find the lower cost option, comparing costs of testing and treatment, as needed, for mothers and infants with the lifetime societal costs without testing and the consequent morbidity and mortality due to lack of treatment or late treatment. We found that maternal screening, infant testing, and treatment of Chagas disease in the United States are cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence above 0.06% compared with no screening program. Newly approved diagnostics make universal screening cost saving with maternal prevalence as low as 0.008%. The present value of lifetime societal savings due to screening and treatment is about $634 million saved for every birth year cohort. The benefits of universal screening for T. cruzi as part of routine prenatal testing far outweigh the program costs for all U.S. births.}, }
@article {pmid29712976, year = {2018}, author = {Hoel, H and Hove-Skovsgaard, M and Hov, JR and Gaardbo, JC and Holm, K and Kummen, M and Rudi, K and Nwosu, F and Valeur, J and Gelpi, M and Seljeflot, I and Ueland, PM and Gerstoft, J and Ullum, H and Aukrust, P and Nielsen, SD and Trøseid, M}, title = {Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {6725}, pmid = {29712976}, issn = {2045-2322}, mesh = {Arginine/analogs &amp; derivatives/metabolism ; Cardiovascular Diseases/genetics/metabolism/*microbiology ; Diabetes Mellitus, Type 2/complications/genetics/metabolism/*microbiology ; Endothelium/metabolism/microbiology/pathology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; HIV Infections/complications/genetics/metabolism/*microbiology ; Humans ; Inflammation/genetics/metabolism/*microbiology ; Kynurenine/metabolism ; Male ; Metabolism/genetics ; Middle Aged ; Neopterin/metabolism ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; Tryptophan/metabolism ; }, abstract = {HIV infection and type 2 diabetes are associated with altered gut microbiota, chronic inflammation, and increased cardiovascular risk. We aimed to investigate the combined effect of these diseases on gut microbiota composition and related metabolites, and a potential relation to endothelial dysfunction in individuals with HIV-infection only (n = 23), diabetes only (n = 16) or both conditions (n = 21), as well as controls (n = 24). Fecal microbiota was analyzed by Illumina sequencing of the 16 S rRNA gene. Markers of endothelial dysfunction (asymmetric dimethylarginine [ADMA]), tryptophan catabolism (kynurenine/tryptophan [KT]-ratio), and inflammation (neopterin) were measured by liquid chromatography-tandem mass spectrometry. The combination of HIV and type 2 diabetes was associated with reduced gut microbiota diversity, increased plasma KT-ratio and neopterin. Microbial genes related to tryptophan metabolism correlated with KT-ratio and low alpha diversity, in particular in HIV-infected with T2D. In multivariate analyses, KT-ratio associated with ADMA (β = 4.58 [95% CI 2.53-6.63], p < 0.001), whereas microbiota composition per se was not associated with endothelial dysfunction. Our results indicate that tryptophan catabolism may be related to endothelial dysfunction, with a potentially detrimental interaction between HIV and diabetes. The potential contribution of gut microbiota and the impact for cardiovascular risk should be further explored in prospective studies powered for clinical end points.}, }
@article {pmid29709869, year = {2018}, author = {Gardiner, BJ and Thorpe, CM and Pinkham, NV and McDermott, LA and Walk, ST and Snydman, DR}, title = {A repeat offender: Recurrent extraintestinal Clostridium difficile infection following fecal microbiota transplantation.}, journal = {Anaerobe}, volume = {51}, number = {}, pages = {68-72}, doi = {10.1016/j.anaerobe.2018.04.007}, pmid = {29709869}, issn = {1095-8274}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/classification/genetics/*isolation &amp; purification ; Clostridium Infections/*epidemiology ; Fecal Microbiota Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Whole Genome Sequencing ; }, abstract = {Extraintestinal infection with Clostridium difficile has been reported but remains uncommon. Treatment of this unusual complication is complex given the limitations of current therapeutic options. Here we report a novel case of recurrent extraintestinal C. difficile infection that occurred following fecal microbiota transplantation. Using whole genome sequencing, we confirmed recrudescence rather than reinfection was responsible. The patient ultimately responded to prolonged, targeted antimicrobial therapy informed by susceptibility testing.}, }
@article {pmid29705917, year = {2018}, author = {Nardelli, S and Ridola, L and Gioia, S and Riggio, O}, title = {Management of Hepatic Encephalopathy Not Responsive to First-Line Treatments.}, journal = {Current treatment options in gastroenterology}, volume = {16}, number = {2}, pages = {253-259}, pmid = {29705917}, issn = {1092-8472}, abstract = {PURPOSE OF REVIEW: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that occurs in up to 30% of patients with cirrhosis. HE may be a consequence of pure liver failure, as in patients with fulminant hepatitis, or of the combination of liver failure and portal-systemic shunting, as in patients with liver cirrhosis. Episodes of HE are usually related to precipitating events, such as infections or gastrointestinal bleeding; a minority of cirrhotic patients experienced a chronic HE, refractory to standard medical treatment. The prevention of HE recurrence, after the first episode of HE, could be obtained by the administration of prophylactic therapy with lactulose, rifaximin or a combination of both. The aim of this review is to clarify some key points in the management of cirrhotic patients with HE, not responsive to first line treatment.<br><br>RECENT FINDINGS: Recent studies investigated the role of fecal microbiota transplantation in the treatment of HE with promising results, but further investigations are needed. In a cirrhotic patient with acute cognitive impairment, the correct diagnosis of HE, after excluding other causes of neurological diseases, is mandatory for the correct management of the precipitating factors and for the treatment. In patients not responsive to standard treatment, the probable precipitating factors have not been correctly identified, multiple precipitating events are coexisting or a new precipitating event is superimposed. In some patients with recurrent HE, characterized by persistent alterations in neurological symptoms, without specific precipitants events, the presence of spontaneous or iatrogenic shunts should be investigated.}, }
@article {pmid29705121, year = {2018}, author = {Sun, MF and Shen, YQ}, title = {Dysbiosis of gut microbiota and microbial metabolites in Parkinson's Disease.}, journal = {Ageing research reviews}, volume = {45}, number = {}, pages = {53-61}, doi = {10.1016/j.arr.2018.04.004}, pmid = {29705121}, issn = {1872-9649}, mesh = {Animals ; Brain/*metabolism ; Dysbiosis/*metabolism/*microbiology ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/metabolism/microbiology ; Humans ; Inflammation/metabolism/microbiology ; Parkinson Disease/*metabolism/*microbiology ; }, abstract = {Gut microbial dysbiosis and alteration of microbial metabolites in Parkinson's disease (PD) have been increasingly reported. Dysbiosis in the composition and abundance of gut microbiota can affect both the enteric nervous system and the central nervous system (CNS), indicating the existence of a microbiota-gut-brain axis and thereby causing CNS diseases. Disturbance of the microbiota-gut-brain axis has been linked to specific microbial products that are related to gut inflammation and neuroinflammation. Future directions should therefore focus on the exploration of specific gut microbes or microbial metabolites that contribute to the development of PD. Microbiota-targeted interventions, such as antibiotics, probiotics and fecal microbiota transplantation, have been shown to favorably affect host health. In this review, recent findings regarding alterations and the role of gut microbiota and microbial metabolites in PD are summarized, and potential molecular mechanisms and microbiota-targeted interventions in PD are discussed.}, }
@article {pmid29703976, year = {2018}, author = {Olesen, SW and Leier, MM and Alm, EJ and Kahn, SA}, title = {Searching for superstool: maximizing the therapeutic potential of FMT.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {15}, number = {7}, pages = {387-388}, doi = {10.1038/s41575-018-0019-4}, pmid = {29703976}, issn = {1759-5053}, mesh = {Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Microbiota ; }, }
@article {pmid29703851, year = {2018}, author = {Kragsnaes, MS and Kjeldsen, J and Horn, HC and Munk, HL and Pedersen, FM and Holt, HM and Pedersen, JK and Holm, DK and Glerup, H and Andersen, V and Fredberg, U and Kristiansen, K and Christensen, R and Ellingsen, T}, title = {Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial.}, journal = {BMJ open}, volume = {8}, number = {4}, pages = {e019231}, pmid = {29703851}, issn = {2044-6055}, mesh = {Antirheumatic Agents ; *Arthritis, Psoriatic/therapy ; Canada ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Humans ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: An unbalanced intestinal microbiota may mediate activation of the inflammatory pathways seen in psoriatic arthritis (PsA). A randomised, placebo-controlled trial of faecal microbiota transplantation (FMT) infused into the small intestine of patients with PsA with active peripheral disease who are non-responsive to methotrexate (MTX) treatment will be conducted. The objective is to explore clinical aspects associated with FMT performed in patients with PsA.<br><br>METHODS AND ANALYSIS: This trial is a randomised, two-centre stratified, double-blind (patient, care provider and outcome assessor), placebo-controlled, parallel-group study. Eighty patients will be included and randomised (1:1) to either placebo (saline) or FMT provided from an anonymous healthy donor. Throughout the study, both groups will continue the weekly self-administered subcutaneous MTX treatment, remaining on the preinclusion dosage (15-25&#x2009;mg/week). The clinical measures of psoriasis and PsA disease activity used include the Short (2-page) Health Assessment Questionnaire, the Dermatology Quality of Life Index, the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Psoriasis Area Severity Index, a dactylitis digit count, a swollen/tender joint count (66/68), plasma C reactive protein as well as visual analogue scales for pain, fatigue and patient and physician global assessments. The primary end point is the proportion of patients who experience treatment failure during the 6-month trial period. The number of adverse events will be registered throughout the study.<br><br>ETHICS AND DISSEMINATION: This is a proof-of-concept clinical trial and will be performed in agreement with Good Clinical Practice standards. Approvals have been obtained from the local Ethics Committee (DK-S-20150080) and the Danish Data Protection Agency (15/41684). The study has commenced in May 2017. Dissemination will be through presentations at national and international conferences and through publications in international peer-reviewed journal(s).<br><br>TRIAL REGISTRATION NUMBER: NCT03058900; Pre-results.}, }
@article {pmid29703246, year = {2018}, author = {Dow, DE and Seed, PC}, title = {Clostridium difficile cure with fecal microbiota transplantation in a child with Pompe disease: a case report.}, journal = {Journal of medical case reports}, volume = {12}, number = {1}, pages = {112}, pmid = {29703246}, issn = {1752-1947}, mesh = {Anti-Bacterial Agents/administration &amp; dosage ; Clostridioides difficile/isolation &amp; purification ; Diarrhea/therapy ; Enterocolitis, Pseudomembranous/diagnosis/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Glycogen Storage Disease Type II/*complications ; Humans ; Immunocompetence ; Infant ; Metronidazole/administration &amp; dosage ; Polymerase Chain Reaction ; Treatment Outcome ; Vancomycin/administration &amp; dosage ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection is a growing problem among children due to both the increasing survival of medically fragile children with complicated chronic medical conditions resulting in prolonged antibiotic exposure and hospitalization and the emergence of strains of Clostridium difficile that are hypervirulent and associated with high rates of relapse.<br><br>CASE PRESENTATION: This case describes a medically complex 21-month-old Hispanic girl with Pompe disease and B cell immunodeficiency with recurrent Clostridium difficile infection refractory to antimicrobial management. She presented with nine recurrent episodes of Clostridium difficile infection including fever, foul smelling diarrhea, and respiratory distress with failed sustained responses to compliant treatment using metronidazole and pulsed vancomycin therapy. Maternal donor fecal microbiota transplantation was performed with complete symptom resolution and produced a sustained cure, now 5 years in duration.<br><br>CONCLUSIONS: This patient presented with symptomatic Clostridium difficile at an early age causing significant morbidity and reduced quality of life. After nearly one year of failed medical management, fecal microbiota transplantation provided a cure. Further evidence-based research is necessary to test the safety and efficacy of this low technology, low cost, and morbidity-sparing therapy in children.}, }
@article {pmid29702430, year = {2018}, author = {Bogiatzi, C and Gloor, G and Allen-Vercoe, E and Reid, G and Wong, RG and Urquhart, BL and Dinculescu, V and Ruetz, KN and Velenosi, TJ and Pignanelli, M and Spence, JD}, title = {Metabolic products of the intestinal microbiome and extremes of atherosclerosis.}, journal = {Atherosclerosis}, volume = {273}, number = {}, pages = {91-97}, doi = {10.1016/j.atherosclerosis.2018.04.015}, pmid = {29702430}, issn = {1879-1484}, support = {133416//CIHR/Canada ; }, mesh = {Aged ; Carotid Artery Diseases/diagnostic imaging/*metabolism/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Severity of Illness Index ; Ultrasonography ; }, abstract = {BACKGROUND AND AIMS: There is increasing awareness that the intestinal microbiome plays an important role in human health. We investigated its role in the burden of carotid atherosclerosis, measured by ultrasound as total plaque area.<br><br>METHODS: Multiple regression with traditional risk factors was used to identify three phenotypes among 316/3056 patients attending vascular prevention clinics. Residual score (RES; i.e. the distance off the regression line, similar to standard deviation) was used to identify the 5% of patients with much less plaque than predicted by their risk factors (Protected, RES <-2), the 90% with about as much plaque as predicted (Explained, RES -2 to 2), and the 5% with much more plaque than predicted (Unexplained RES >2). Metabolic products of the intestinal microbiome that accumulate in renal failure - gut-derived uremic toxins (GDUT) - were assayed in plasma by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.<br><br>RESULTS: Plasma levels of trimethylamine n-oxide (TMAO), p-cresyl sulfate, p-cresyl glucuronide, and phenylacetylglutamine were significantly lower among patients with the Protected phenotype, and higher in those with the Unexplained phenotype, despite no significant differences in renal function or in dietary intake of nutrient precursors of GDUT. In linear multiple regression with a broad panel of risk factors, TMAO (p&#x202f;=&#x202f;0.011) and p-cresyl sulfate (p&#x202f;=&#x202f;0.011) were significant independent predictors of carotid plaque burden.<br><br>CONCLUSIONS: The intestinal microbiome appears to play an important role in atherosclerosis. These findings raise the possibility of novel approaches to treatment of atherosclerosis such as fecal transplantation and probiotics.}, }
@article {pmid29696802, year = {2018}, author = {D'Odorico, I and Di Bella, S and Monticelli, J and Giacobbe, DR and Boldock, E and Luzzati, R}, title = {Role of fecal microbiota transplantation in inflammatory bowel disease.}, journal = {Journal of digestive diseases}, volume = {19}, number = {6}, pages = {322-334}, doi = {10.1111/1751-2980.12603}, pmid = {29696802}, issn = {1751-2980}, mesh = {Donor Selection ; Fecal Microbiota Transplantation/adverse effects/*methods ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Tissue Donors ; Treatment Outcome ; }, abstract = {There is increasing evidence of the key role played by altered intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD). Management strategies involving immune modulation are effective and widely used, but treatment failures and side effects occur. Fecal microbiota transplantation (FMT) provides a novel, perhaps complementary, strategy to restore the normal gut microbiota in patients with IBD. This review summarizes the available efficacy and safety data on the use of FMT in patients with IBD. Several aspects remain to be clarified about the clinical predictors of the response to FMT, its most appropriate route of administration, and the most appropriate quantity and quality of microbiota to be transplanted. Further studies focusing on long-term outcomes and safety are also warranted.}, }
@article {pmid29694952, year = {2018}, author = {Enck, P and Mazurak, N}, title = {Dysbiosis in Functional Bowel Disorders.}, journal = {Annals of nutrition &amp; metabolism}, volume = {72}, number = {4}, pages = {296-306}, doi = {10.1159/000488773}, pmid = {29694952}, issn = {1421-9697}, mesh = {Dysbiosis/*complications ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/complications/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/complications/microbiology ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {Functional bowel disorders (FBD) resemble a group of diseases of the gastrointestinal (GI) tract that are without a clear pathogenesis; the best known is probably the "irritable bowel syndrome" (IBS). Only recently we have been able to explore the role of the gut microbiota in FBD due to progress in microbiological analytic techniques. There are different ways to explore the role of the gut microbiota and its dysbiosis in FBD. Comparison of the microbial composition in a group of patients with FBD, for example, with IBS to a group of healthy volunteers is one way. Studies have shown that the microbiota in FBD is different from that of healthy controls, but the recorded differences are not necessarily specific for FBD, they may also occur in other diseases. Another approach to explore the role of the gut microbiota in FBD is to challenge the existing "flora" with novel bacteria (probiotics) or with nutritional substrates that stimulate bacterial growth (prebiotics). More than 60 such trials including several thousand patients have been performed in IBS. These studies have produced mixed outcome: some probiotics appear to be better than others, and some appear to work only for a part of the IBS symptoms and not for all. An extreme form of this approach is the transfer of an entire microbiota from 1 healthy person to another, called fecal microbiota transplantation. This has rarely been tested in FBD but is not without risk in benign disorders.}, }
@article {pmid29691757, year = {2018}, author = {Zhang, F and Cui, B and He, X and Nie, Y and Wu, K and Fan, D and , }, title = {Microbiota transplantation: concept, methodology and strategy for its modernization.}, journal = {Protein &amp; cell}, volume = {9}, number = {5}, pages = {462-473}, pmid = {29691757}, issn = {1674-8018}, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods/*standards ; Host Microbial Interactions ; Humans ; Inflammatory Bowel Diseases/*therapy ; Metabolic Diseases/*therapy ; }, abstract = {Fecal microbiota transplantation (FMT) has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut-brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT to selective microbiota transplantation, methodology development of FMT and step-up FMT strategy based on literature and state experts' perspectives.}, }
@article {pmid29688915, year = {2019}, author = {Francavilla, R and Piccolo, M and Francavilla, A and Polimeno, L and Semeraro, F and Cristofori, F and Castellaneta, S and Barone, M and Indrio, F and Gobbetti, M and De Angelis, M}, title = {Clinical and Microbiological Effect of a Multispecies Probiotic Supplementation in Celiac Patients With Persistent IBS-type Symptoms: A Randomized, Double-Blind, Placebo-controlled, Multicenter Trial.}, journal = {Journal of clinical gastroenterology}, volume = {53}, number = {3}, pages = {e117-e125}, pmid = {29688915}, issn = {1539-2031}, mesh = {Adolescent ; Adult ; Celiac Disease/*diet therapy ; *Diet, Gluten-Free ; Double-Blind Method ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*diet therapy/physiopathology ; Male ; Middle Aged ; Probiotics/*administration &amp; dosage ; Prospective Studies ; Quality of Life ; Surveys and Questionnaires ; Treatment Outcome ; Young Adult ; }, abstract = {GOALS: The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD).<br><br>BACKGROUND: About 30% of patients with CD adherent to a GFD suffer from IBS-type symptoms; a possible cause resides in the imbalances of the intestinal microbiota in CD. Probiotics may represent a potential treatment.<br><br>STUDY: CD patients with IBS-type symptoms entered a prospective, double-blind, randomized placebo-controlled study. A 6-week treatment period was preceded by a 2-week run-in and followed by a 6-week follow-up phase. Clinical data were monitored throughout the study by validated questionnaires: IBS Severity Scoring System (IBS-SSS); Gastrointestinal Symptom Rating Scale (GSRS); Bristol Stool Form Scale (BSFS); and IBS Quality of Life Questionnaire (IBS-QOL). The fecal microbiota were assayed using plate counts and 16S rRNA gene-based analysis.<br><br>RESULTS: In total, 109 patients were randomized to probiotics (n=54) or placebo (n=55). IBS-SSS and GSRS decreased significantly in probiotics, as compared with placebo [(-15.9%&#xb1;14.8% vs. 8.2%&#xb1;25.9%; P<0.001) and (-19.8%&#xb1;16.6% vs. 12.9%&#xb1;31.6%; P<0.001)], respectively. Treatment success was significantly higher in patients receiving probiotics, as compared with placebo (15.3% vs. 3.8%; P<0.04). Presumptive lactic acid bacteria, Staphylococcus and Bifidobacterium, increased in patients receiving probiotic treatment. No adverse events were reported.<br><br>CONCLUSIONS: A 6-week probiotic treatment is effective in improving the severity of IBS-type symptoms, in CD patients on strict GFD, and is associated with a modification of gut microbiota, characterized by an increase of bifidobacteria.}, }
@article {pmid29688901, year = {2018}, author = {Iqbal, U and Anwar, H and Karim, MA}, title = {Safety and efficacy of encapsulated fecal microbiota transplantation for recurrent Clostridium difficile infection: a systematic review.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {30}, number = {7}, pages = {730-734}, doi = {10.1097/MEG.0000000000001147}, pmid = {29688901}, issn = {1473-5687}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Retreatment ; Risk Factors ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND AND AIMS: Fecal microbial transplantation (FMT) has been shown to be effective for the treatment of recurrent clostridium difficile infection (CDI). The efficacy and safety of freeze-dried encapsulated FMT for the treatment of recurrent CDI is unclear. We performed a systematic review to evaluate and analyze the current evidence in this respect.<br><br>MATERIALS AND METHODS: A systematic literature search was performed using the PubMed, Embase, and Medline databases until December 2017 to identify all original studies that investigated the role of administration of encapsulated FMT in recurrent CDI. The study included patients of all ages. Two independent reviewers extracted data and assessed the quality of publications; a third investigator resolved any discrepancies.<br><br>RESULTS: A total of six studies, five case series and one randomized-controlled trial, were included in this review. Overall, 341 patients completed treatment with encapsulated FMT. Only three major adverse events were reported and no deaths occurred directly related to FMT. In all, 285 patients responded to the first treatment, with no recurrence during the specified follow-up period set to meet the primary endpoint. Forty-two patients underwent a second treatment, with resolution of symptoms in 28 patients. At least five patients were reported to undergo a third treatment, with resolution in three of them. Only one patient was reported to have received four treatments without long-term resolution of symptoms.<br><br>CONCLUSION: Low-quality to moderate-quality evidence showed that encapsulated FMT is safe and cost-effective for the treatment and prevention of recurrent CDI. Its efficacy is not inferior to FMT performed through the nonoral route. Randomized-controlled trials are necessary to compare its efficacy with oral antimicrobial drugs and also to evaluate the potential adverse effects associated with the treatment.}, }
@article {pmid29687200, year = {2019}, author = {Hong, M and Han, DH and Hong, J and Kim, DJ and Suk, KT}, title = {Are Probiotics Effective in Targeting Alcoholic Liver Diseases?.}, journal = {Probiotics and antimicrobial proteins}, volume = {11}, number = {2}, pages = {335-347}, pmid = {29687200}, issn = {1867-1314}, mesh = {Animals ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Liver Diseases, Alcoholic/*drug therapy/microbiology ; Mice ; Mice, Inbred C57BL ; Probiotics/*therapeutic use ; Toll-Like Receptor 4/physiology ; }, abstract = {Alcoholic liver disease (ALD) encompasses a broad spectrum of disorders including steatosis, steatohepatitis, fibrosis, and cirrhosis. Despite intensive research in the last two decades, there is currently no Food and Drug Administration-approved therapy for treating ALD. Several studies have demonstrated the importance of the gut-liver axis and gut microbiome on the pathogenesis of ALD. Alcohol may induce intestinal dysbiosis and increased intestinal permeability, which in turn result in increased levels of pathogen-associated molecular patterns such as lipopolysaccharide (LPS) and translocation of microbial products from the gut to the liver (bacterial translocation). LPS is an inflammatory signal that activates toll-like receptor 4 on Kupffer cells, contributing to the inflammation observed in ALD. Recently, probiotics have been shown to be effective in reducing or preventing the progression of ALD. A potential mechanism is that the probiotics transforms the composition of intestinal microbiota, which leads to reductions in alcohol-induced dysbiosis, intestinal permeability, bacterial translocation, endotoxemia, and consequently, the development of ALD. While transformation of intestinal microbiota by probiotics appears to be a promising therapeutic strategy for the treatment of intestinal barrier dysfunction, there is a scarcity of research that studies probiotics in the context of ALD. In this review, we discuss the potential therapeutic applications of probiotics in the treatment of ALD.}, }
@article {pmid29685195, year = {2018}, author = {Tirandaz, H and Ebrahim-Habibi, MB and Moradveisi, B and Raoofi, S and Salehi-Najafabadi, A and Mohammadi, E}, title = {Microbiota potential for the treatment of sexual dysfunction.}, journal = {Medical hypotheses}, volume = {115}, number = {}, pages = {46-49}, doi = {10.1016/j.mehy.2018.03.021}, pmid = {29685195}, issn = {1532-2777}, mesh = {Animals ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Male ; Microbiota/*physiology ; Models, Biological ; Prebiotics ; Probiotics/therapeutic use ; Sexual Dysfunction, Physiological/*microbiology/*therapy ; Sexuality/physiology ; }, abstract = {Inability to have a satisfactory sexual intercourse is a serious problem affecting many people. Despite enormous efforts for developing effective treatments for pathologic conditions associated with sexual malfunction, still a lot of patients do not respond well to such treatments. Microbiota has been shown to affect obesity, diabetes, hypertension, stress/anxiety and sex hormonal disturbances. Nevertheless, no research has concentrated on the link between microbiota and human sexuality or sexual dysfunction. We propose another line of enquiry into sexual dysfunction by hypothesizing a relationship between microbiota and factors affecting human sexuality. Hence, it can be assumed that microbiota manipulation may improve sexual behavior and reduce sexual dysfunction. We also discuss the evidence to back up this hypothesis, and present some predictions.}, }
@article {pmid29684976, year = {2018}, author = {Giron, F and Quigley, EMM}, title = {Pharmabiotic Manipulation of the Microbiota in Gastrointestinal Disorders: A Clinical Perspective.}, journal = {Journal of neurogastroenterology and motility}, volume = {24}, number = {3}, pages = {355-366}, pmid = {29684976}, issn = {2093-0879}, abstract = {The advent and widespread availability of high-throughput technology has revolutionized the assessment of the communities of microorganisms that inhabit the gastrointestinal tract-the gut microbiota. As our understanding of the role of the microbiota in health and human disease increases, so also do efforts to prevent and treat disease through the modulation of the microbiota. Several strategies are available to us and range from time honored approaches, such as antibiotics and probiotics, to changes in diet, the administration of prebiotics as food supplements, and fecal microbiota transplantation. Of these, diet is perhaps the most pervasive but often ignored modulator of the microbiota, and a failure to recognize its impact complicates the interpretation of many microbiota studies. The impacts of antibiotics on the microbiota are more complex than originally thought and, though antibiotics can be life-saving, their effects on commensal bacterial populations can be clinically significant. Though there have been many studies of, and even more claims made for, probiotics, the majority of available studies suffer from significant deficits in study design and execution and many claims remain to be substantiated. Though holding much promise, the study of prebiotics in human disease is still in its infancy. Possibilities other than the administration of live organisms have been identified through efforts to mine the microbiota for novel therapeutics and include: dead organisms, bacterial components, small molecules elaborated by bacteria, and even bacterial DNA. Accordingly, the term pharmabiotic has been introduced to encompass the full range of therapeutic possibilities that the microbiota offers.}, }
@article {pmid29684865, year = {2018}, author = {Kurokawa, S and Kishimoto, T and Mizuno, S and Masaoka, T and Naganuma, M and Liang, KC and Kitazawa, M and Nakashima, M and Shindo, C and Suda, W and Hattori, M and Kanai, T and Mimura, M}, title = {The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study.}, journal = {Journal of affective disorders}, volume = {235}, number = {}, pages = {506-512}, doi = {10.1016/j.jad.2018.04.038}, pmid = {29684865}, issn = {1573-2517}, mesh = {Adult ; Anxiety Disorders/*psychology ; Constipation/psychology/*therapy ; Depressive Disorder/*psychology ; Diarrhea/psychology/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Gastrointestinal Diseases ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/psychology/*therapy ; Male ; Middle Aged ; }, abstract = {BACKGROUNDS: The intestinal microbiota is considered as a potential common underpinning pathophysiology of Functional Gastrointestinal Disorders (FGIDs) and psychiatric disorders such as depression and anxiety. Fecal Microbiota Transplantation (FMT) has been reported to have therapeutic effects on diseases related to dysbiosis, but few studies have evaluated its effect on psychiatric symptoms.<br><br>METHODS: We followed 17 patients with either Irritable Bowel Syndrome (IBS), Functional Diarrhea (FDr) or Functional Constipation (FC) who underwent FMT for the treatment of gastrointestinal symptoms and observation of psychiatric symptoms. Changes in Hamilton Rating Scale for Depression (HAM-D) and subscale of sleep-related items, Hamilton Rating Scale for Anxiety (HAM-A) and Quick Inventory for Depressive Symptoms (QIDS) between baseline and 4 weeks after FMT, and relationship with the intestinal microbiota were measured.<br><br>RESULTS: At baseline, 12 out of 17 patients were rated with HAM-D&#x202f;&#x2265;&#x202f;8. Significant improvement in HAM-D total and sleep subscale score, HAM-A and QIDS were observed (p&#x202f;=&#x202f;0.007, p&#x202f;=&#x202f;0.007, p&#x202f;=&#x202f;0.01, p&#x202f;=&#x202f;0.007, respectively). Baseline Shannon index indicated that microbiota showed lower diversity in patients with HAM-D&#x202f;&#x2265;&#x202f;8 compared to those of healthy donors and patients with HAM-D&#x202f;<&#x202f;8. There was a significant correlation between baseline Shannon index and HAM-D score, and a correlation between Shannon index change and HAM-D improvement after FMT.<br><br>LIMITATIONS: The small sample size with no control group.<br><br>CONCLUSIONS: Our results suggest that depression and anxiety symptoms may be improved by FMT regardless of gastrointestinal symptom change in patients with IBS, FDr and FC, and the increase of microbiota diversity may help to improve patient's mood.}, }
@article {pmid29682542, year = {2018}, author = {Vemuri, R and Gundamaraju, R and Shastri, MD and Shukla, SD and Kalpurath, K and Ball, M and Tristram, S and Shankar, EM and Ahuja, K and Eri, R}, title = {Gut Microbial Changes, Interactions, and Their Implications on Human Lifecycle: An Ageing Perspective.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {4178607}, pmid = {29682542}, issn = {2314-6141}, mesh = {Aging/drug effects/*immunology/*physiology ; Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Gastrointestinal Microbiome/drug effects/*immunology/*physiology ; Gastrointestinal Tract/drug effects/immunology/microbiology ; Humans ; Immune System/immunology ; Life Cycle Stages/drug effects/*immunology/*physiology ; Prebiotics ; Probiotics/pharmacology/therapeutic use ; }, abstract = {Gut microbiota is established during birth and evolves with age, mostly maintaining the commensal relationship with the host. A growing body of clinical evidence suggests an intricate relationship between the gut microbiota and the immune system. With ageing, the gut microbiota develops significant imbalances in the major phyla such as the anaerobic Firmicutes and Bacteroidetes as well as a diverse range of facultative organisms, resulting in impaired immune responses. Antimicrobial therapy is commonly used for the treatment of infections; however, this may also result in the loss of normal gut flora. Advanced age, antibiotic use, underlying diseases, infections, hormonal differences, circadian rhythm, and malnutrition, either alone or in combination, contribute to the problem. This nonbeneficial gastrointestinal modulation may be reversed by judicious and controlled use of antibiotics and the appropriate use of prebiotics and probiotics. In certain persistent, recurrent settings, the option of faecal microbiota transplantation can be explored. The aim of the current review is to focus on the establishment and alteration of gut microbiota, with ageing. The review also discusses the potential role of gut microbiota in regulating the immune system, together with its function in healthy and diseased state.}, }
@article {pmid29679429, year = {2018}, author = {Paula, FM and Malta, FM and Marques, PD and Melo, GB and Corral, MA and Gottardi, M and Pinho, JRR and Gonçalves, EMN and Castilho, VLP and Pierrotti, LC and Abdala, E and Costa, SF and Chieffi, PP and Gryschek, RCB}, title = {Molecular diagnosis of Strongyloides stercoralis among transplant candidates.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {20}, number = {4}, pages = {e12909}, doi = {10.1111/tid.12909}, pmid = {29679429}, issn = {1399-3062}, mesh = {Animals ; Brazil/epidemiology ; DNA, Helminth/*isolation &amp; purification ; Feces/*parasitology ; Genes, rRNA/genetics ; Humans ; Immunocompromised Host ; Larva ; Prevalence ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity ; Sequence Analysis, DNA/*methods ; Strongyloides stercoralis/genetics/*isolation &amp; purification ; Strongyloidiasis/*diagnosis/epidemiology/immunology/parasitology ; Transplantation/adverse effects ; }, abstract = {Strongyloidiasis can occur without any symptoms or as a potentially fatal hyperinfection or disseminated infection, principally in immunosuppressed patients. Our study aimed to evaluate the application of conventional polymerase chain reaction (cPCR) and real-time PCR (qPCR). Polymerase chain reaction (PCR) and real-time PCR (qPCR) targeting the 18S rRNA gene for detection of Strongyloides stercoralis infection among transplant candidates were applied in stool samples obtained from 150 transplant candidates, preliminarily analyzed by parasitological methods. S. stercoralis larvae were visualized in 15/150 (10.0%) transplant candidates by parasitological methods. DNA from S. stercoralis was amplified in 26/150 (17.3%) and 49/150 (32.7%) stool samples of transplant candidates, using cPCR and qPCR, respectively. The results suggest that molecular methods, especially qPCR, should be used as an additional tool for diagnostic of S. stercoralis infection among transplant candidates.}, }
@article {pmid29676108, year = {2018}, author = {Du, H and Xu, T and Li, HJ and Li, Q and GangHuan, CL and Fan, G and Zhang, Y}, title = {[Fecal Tibetan medicines].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {43}, number = {5}, pages = {1054-1061}, doi = {10.19540/j.cnki.cjcmm.20171212.001}, pmid = {29676108}, issn = {1001-5302}, mesh = {China ; *Feces ; *Gastrointestinal Microbiome ; *Medicine, Tibetan Traditional ; }, abstract = {Fecal Tibetan medicines have a long history of application in China, with a good clinical efficacy. In order to promote the development and modernization of these medicines, we consulted ancient and modern Tibetan medicine literatures to collect and summarize the names, original species, natures, flavor, functions and processing methods of fecal Tibetan medicines. A total of 35 fecal Tibetan medicines were collected, such as Jiufen, Heibingpian, Langfen, Mafen, Goufen, Gezifen. The most commonly used medicines were Jiufen and Heibingpian. Both were mainly used for the treatment of indigestion, food abdominal distension, gastric ulcer, and other gastrointestinal diseases. At present, there are only a few studies on the active ingredients, pharmacodynamics and mechanism of action of these medicines. Therefore, further study shall be conducted. The regulation of gut microbiota may be a new way to evaluate the effectiveness of fecal Tibetan medicines and their mechanism of action.}, }
@article {pmid29674425, year = {2018}, author = {Haak, BW and Littmann, ER and Chaubard, JL and Pickard, AJ and Fontana, E and Adhi, F and Gyaltshen, Y and Ling, L and Morjaria, SM and Peled, JU and van den Brink, MR and Geyer, AI and Cross, JR and Pamer, EG and Taur, Y}, title = {Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT.}, journal = {Blood}, volume = {131}, number = {26}, pages = {2978-2986}, pmid = {29674425}, issn = {1528-0020}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Bacteria/*metabolism ; Butyrates/*metabolism ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Protective Factors ; Respiratory Tract Infections/*etiology/metabolism/*microbiology ; Transplantation, Homologous/adverse effects ; Virus Diseases/*etiology/metabolism/*microbiology ; }, abstract = {Respiratory viral infections are frequent in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) and can potentially progress to lower respiratory tract infection (LRTI). The intestinal microbiota contributes to resistance against viral and bacterial pathogens in the lung. However, whether intestinal microbiota composition and associated changes in microbe-derived metabolites contribute to the risk of LRTI following upper respiratory tract viral infection remains unexplored in the setting of allo-HCT. Fecal samples from 360 allo-HCT patients were collected at the time of stem cell engraftment and subjected to deep, 16S ribosomal RNA gene sequencing to determine microbiota composition, and short-chain fatty acid levels were determined in a nested subset of fecal samples. The development of respiratory viral infections and LRTI was determined for 180 days following allo-HCT. Clinical and microbiota risk factors for LRTI were subsequently evaluated using survival analysis. Respiratory viral infection occurred in 149 (41.4%) patients. Of those, 47 (31.5%) developed LRTI. Patients with higher abundances of butyrate-producing bacteria were fivefold less likely to develop viral LRTI, independent of other factors (adjusted hazard ratio = 0.22, 95% confidence interval 0.04-0.69). Higher representation of butyrate-producing bacteria in the fecal microbiota is associated with increased resistance against respiratory viral infection with LRTI in allo-HCT patients.}, }
@article {pmid29674329, year = {2018}, author = {Hota, SS and Surangiwala, S and Paterson, AS and Coburn, B and Poutanen, SM and , }, title = {Regional variability in fecal microbiota transplantation practices: a survey of the Southern Ontario Fecal Microbiota Transplantation Movement.}, journal = {CMAJ open}, volume = {6}, number = {2}, pages = {E184-E190}, pmid = {29674329}, issn = {2291-0026}, abstract = {BACKGROUND: There is growing evidence that fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection, but little guidance exists for implementation of FMT programs. The objective of this study is to describe the program characteristics and protocols of 9 planned or operating FMT programs in the Southern Ontario Fecal Microbiota Transplantation (SOFT) Movement, to help guide future FMT program implementation.<br><br>METHODS: A 59-item survey was administered electronically to clinical leads of the SOFT Movement on June 2, 2016. The survey evaluated 7 domains: FMT program characteristics, FMT recipients, donor screening/selection, transplant manufacturing, FMT administration, good manufacturing procedures/biosafety procedures and infection-control procedures. We used descriptive statistics to analyze quantitative data.<br><br>RESULTS: All 9 programs responded to the survey: 6 were active, 1 had FMT standard operating procedures developed but did not have clinical experience, and 2 were in the process of forming FMT programs. All 6 active programs performed FMT in adult patients with C. difficile infection. About 1300 FMT procedures were performed between 2003 and 2016. Five of the 6 operating programs administered the preparation via enema. Programs were driven primarily by physicians. All programs used universal FMT donors and followed Health Canada's screening guidelines, with considerable variability in screening frequency (every 3-6 mo) and modality. Locations for transplant preparation and manufacturing protocols varied across programs. Stool mass for FMT ranged from 20 g to 150 g, and transplant volume ranged from 25 mL to 300 mL.<br><br>INTERPRETATION: The experience of this high-volume regional FMT network highlights current challenges in FMT program development, including a high reliance on physicians and the costly nature of donor screening. Standardization and optimization through development of regional centres of excellence for FMT donor recruitment and administration should be explored.}, }
@article {pmid29673295, year = {2018}, author = {Groen, RN and de Clercq, NC and Nieuwdorp, M and Hoenders, HJR and Groen, AK}, title = {Gut microbiota, metabolism and psychopathology: A critical review and novel perspectives.}, journal = {Critical reviews in clinical laboratory sciences}, volume = {55}, number = {4}, pages = {283-293}, doi = {10.1080/10408363.2018.1463507}, pmid = {29673295}, issn = {1549-781X}, mesh = {*Brain/metabolism/physiology ; *Gastrointestinal Microbiome ; Homeostasis ; Humans ; *Mental Disorders/metabolism/physiopathology ; Metabolism ; }, abstract = {Psychiatric disorders are often associated with metabolic comorbidities. However, the mechanisms through which metabolic and psychiatric disorders are connected remain unclear. Pre-clinical studies in rodents indicate that the bidirectional signaling between the intestine and the brain, the so-called microbiome-gut-brain axis, plays an important role in the regulation of both metabolism and behavior. The gut microbiome produces a vast number of metabolites that may be transported into the host and play a part in homeostatic control of metabolism as well as brain function. In addition to short chain fatty acids, many of these metabolites have been identified in recent years. To what extent both microbiota and their products control human metabolism and behavior is a subject of intense investigation. In this review, we will discuss the most recent findings concerning alterations in the gut microbiota as a possible pathophysiological factor for the co-occurrence of metabolic comorbidities in psychiatric disorders.}, }
@article {pmid29670863, year = {2018}, author = {Anonye, BO}, title = {Commentary: Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {104}, pmid = {29670863}, issn = {2235-2988}, support = {BB/M017982/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Bacteriophages ; Clostridium Infections ; *Fecal Microbiota Transplantation ; Humans ; Treatment Outcome ; }, }
@article {pmid29670798, year = {2018}, author = {Amlani, A and Bromley, A and Fifi-Mah, A}, title = {ANCA Vasculitis and Hemophagocytic Lymphohistiocytosis following a Fecal Microbiota Transplant.}, journal = {Case reports in rheumatology}, volume = {2018}, number = {}, pages = {9263537}, pmid = {29670798}, issn = {2090-6889}, abstract = {A 69-year-old female with antisynthetase syndrome, a history of multiple recurrent infections, and documented previous negative titres for anti-neutrophil cystoplasmic antibody (ANCA) suddenly developed a de novo MPO-ANCA-associated glomerulonephritis three weeks after a fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infections. Six months following her FMT and less than two weeks following treatment for urosepsis, she developed severe cholestasis, a markedly elevated ferritin and hypertriglyceridemia. An initial liver biopsy was suggestive of drug-induced liver injury and thus she was treated with supportive care. After she failed to improve, a second liver biopsy supported the diagnosis of hemophagocytic lymphohistiocytosis (HLH). This case highlights difficulties surrounding the early diagnosis of HLH and also questions the role of FMT and/or recurrent infections as a trigger for ANCA-associated vasculitis.}, }
@article {pmid29670191, year = {2018}, author = {Le Bastard, Q and Ward, T and Sidiropoulos, D and Hillmann, BM and Chun, CL and Sadowsky, MJ and Knights, D and Montassier, E}, title = {Fecal microbiota transplantation reverses antibiotic and chemotherapy-induced gut dysbiosis in mice.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {6219}, pmid = {29670191}, issn = {2045-2322}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects/pharmacology ; Antineoplastic Agents/*adverse effects/pharmacology ; Biodiversity ; Disease Models, Animal ; Dysbiosis/*etiology/*microbiology/therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Metagenome ; Metagenomics/methods ; Mice ; }, abstract = {Fecal microbiota transplantation (FMT) is now widely used to treat recurrent Clostridium difficile infection, but has been less studied as a means to restore microbiome diversity and composition following antibiotic or chemotherapy treatments. The purpose of our study was to assess the efficacy of FMT to reverse antibiotic- and chemotherapy-induced gut dysbiosis in a mouse model. C57BL/6J mice were treated with ampicillin for 1 week and/or received a single intraperitoneal injection of 5-Fluorouracil. Fresh stool was collected and analyzed using shotgun metagenomics and the Illumina sequencing platform. Ampicillin caused a significant and immediate decrease in bacterial species richness and diversity that persisted for one week. In mice that received FMT, disruption of the intestinal microbiota was reversed immediately. Antibiotic and chemotherapy administration caused significant alteration in species distribution, including a decrease in the relative proportions of Clostridium scindens and Faecalibacterium prausnitzii, and an increase in known pathogenic species. In mice receiving FMT, we observed a significant increase in species known to exhibit anti-inflammatory properties. Moreover, chemotherapy led to a critical decrease in key 'health-promoting' species and to an altered functional profile, especially when chemotherapy was administered in tandem with antibiotics, and that FMT can ameliorate these effects.}, }
@article {pmid29669239, year = {2018}, author = {Wullaert, A and Lamkanfi, M and McCoy, KD}, title = {Defining the Impact of Host Genotypes on Microbiota Composition Requires Meticulous Control of Experimental Variables.}, journal = {Immunity}, volume = {48}, number = {4}, pages = {605-607}, doi = {10.1016/j.immuni.2018.04.001}, pmid = {29669239}, issn = {1097-4180}, mesh = {Animals ; CARD Signaling Adaptor Proteins/genetics ; Caspase 1/*genetics ; Dysbiosis/genetics/*microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Receptors, Cell Surface/*genetics ; }, }
@article {pmid29667487, year = {2018}, author = {Markey, L and Shaban, L and Green, ER and Lemon, KP and Mecsas, J and Kumamoto, CA}, title = {Pre-colonization with the commensal fungus Candida albicans reduces murine susceptibility to Clostridium difficile infection.}, journal = {Gut microbes}, volume = {9}, number = {6}, pages = {497-509}, pmid = {29667487}, issn = {1949-0984}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; R01 AI081794/AI/NIAID NIH HHS/United States ; R01 AI118898/AI/NIAID NIH HHS/United States ; R56 AI081794/AI/NIAID NIH HHS/United States ; T32 AI007422/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Candida albicans/*immunology ; Cecum/immunology/microbiology/pathology ; Clostridioides difficile/immunology/*physiology ; *Clostridium Infections/immunology/microbiology/prevention &amp; control ; Disease Models, Animal ; Disease Susceptibility/*microbiology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology/physiology ; Host Microbial Interactions/*immunology ; Interleukin-17/genetics ; Mice, Inbred C57BL ; Microbial Interactions/immunology/*physiology ; Survival Analysis ; Up-Regulation/genetics ; }, abstract = {Clostridium difficile is a major nosocomial pathogen responsible for close to half a million infections and 27,000 deaths annually in the U.S. Preceding antibiotic treatment is a major risk factor for C. difficile infection (CDI) leading to recognition that commensal microbes play a key role in resistance to CDI. Current antibiotic treatment of CDI is only partially successful due to a high rate of relapse. As a result, there is interest in understanding the effects of microbes on CDI susceptibility to support treatment of patients with probiotic microbes or entire microbial communities (e.g., fecal microbiota transplantation). The results reported here demonstrate that colonization with the human commensal fungus Candida albicans protects against lethal CDI in a murine model. Colonization with C. albicans did not increase the colonization resistance of the host. Rather, our findings showed that one effect of C. albicans colonization was to enhance a protective immune response. Mice pre-colonized with C. albicans expressed higher levels of IL-17A in infected tissue following C. difficile challenge compared to mice that were not colonized with C. albicans. Administration of cytokine IL-17A was demonstrated to be protective against lethal murine CDI in mice not colonized with C. albicans. C. albicans colonization was associated with changes in the abundance of some bacterial components of the gut microbiota. Therefore, C. albicans colonization altered the gut ecosystem, enhancing survival after C. difficile challenge. These findings demonstrate a new, beneficial role for C. albicans gut colonization.}, }
@article {pmid29667436, year = {2018}, author = {Khoruts, A}, title = {Is fecal microbiota transplantation a temporary patch for treatment of Clostridium difficile infection or a new frontier of therapeutics?.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {12}, number = {5}, pages = {435-438}, doi = {10.1080/17474124.2018.1465818}, pmid = {29667436}, issn = {1747-4132}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/drug effects/*pathogenicity ; Clostridium Infections/diagnosis/microbiology/*therapy ; Drug Resistance, Bacterial ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Host-Pathogen Interactions ; Humans ; Treatment Outcome ; }, }
@article {pmid29665135, year = {2019}, author = {Ponziani, FR and Bhoori, S and Castelli, C and Putignani, L and Rivoltini, L and Del Chierico, F and Sanguinetti, M and Morelli, D and Paroni Sterbini, F and Petito, V and Reddel, S and Calvani, R and Camisaschi, C and Picca, A and Tuccitto, A and Gasbarrini, A and Pompili, M and Mazzaferro, V}, title = {Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease.}, journal = {Hepatology (Baltimore, Md.)}, volume = {69}, number = {1}, pages = {107-120}, doi = {10.1002/hep.30036}, pmid = {29665135}, issn = {1527-3350}, support = {//Italian Ministry of Education, Universities and Research/International ; }, mesh = {Aged ; Carcinoma, Hepatocellular/*congenital/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Inflammation/*complications ; Liver Cirrhosis/*complications ; Liver Neoplasms/*complications/*microbiology ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*complications ; }, abstract = {The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides. Conclusion: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis.}, }
@article {pmid29665102, year = {2018}, author = {Bajaj, JS and Kakiyama, G and Savidge, T and Takei, H and Kassam, ZA and Fagan, A and Gavis, EA and Pandak, WM and Nittono, H and Hylemon, PB and Boonma, P and Haag, A and Heuman, DM and Fuchs, M and John, B and Sikaroodi, M and Gillevet, PM}, title = {Antibiotic-Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant.}, journal = {Hepatology (Baltimore, Md.)}, volume = {68}, number = {4}, pages = {1549-1558}, doi = {10.1002/hep.30037}, pmid = {29665102}, issn = {1527-3350}, support = {R21 DK096323/DK/NIDDK NIH HHS/United States ; I01 BX001328/BX/BLRD VA/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; I01 BX000197/BX/BLRD VA/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; }, mesh = {Aged ; Anti-Bacterial Agents/administration &amp; dosage/*adverse effects ; *Drug Resistance, Microbial ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*drug effects ; Humans ; Liver Cirrhosis/pathology/*therapy ; Middle Aged ; Reference Values ; Rifaximin/therapeutic use ; Standard of Care ; Statistics, Nonparametric ; Treatment Outcome ; }, abstract = {UNLABELLED: Patients with cirrhosis are often exposed to antibiotics that can lead to resistance and fungal overgrowth. The role of fecal microbial transplant (FMT) in restoring gut microbial function is unclear in cirrhosis. In a Food and Drug Administration-monitored phase 1 clinical safety trial, patients with decompensated cirrhosis on standard therapies (lactulose and rifaximin) were randomized to standard-of-care (SOC, no antibiotics/FMT) or 5 days of broad-spectrum antibiotics followed by FMT from a donor enriched in Lachnospiraceae and Ruminococcaceae. Microbial composition (diversity, family-level relative abundances), function (fecal bile acid [BA] deconjugation, 7α-dehydroxylation, short-chain fatty acids [SCFAs]), and correlations between Lachnospiraceae, Ruminococcaceae, and clinical variables were analyzed at baseline, postantibiotics, and 15 days post-FMT. FMT was well tolerated. Postantibiotics, there was a reduced microbial diversity and autochthonous taxa relative abundance. This was associated with an altered fecal SCFA and BA profile. Correlation linkage changes from beneficial at baseline to negative after antibiotics. All of these parameters became statistically similar post-FMT to baseline levels. No changes were seen in the SOC group.<br><br>CONCLUSION: In patients with advanced cirrhosis on lactulose and rifaximin, FMT restored antibiotic-associated disruption in microbial diversity and function. (Hepatology 2018; 00:000-000).}, }
@article {pmid29663213, year = {2018}, author = {Klose, G and Ramsauer, B}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {160}, number = {7}, pages = {36}, doi = {10.1007/s15006-018-0426-z}, pmid = {29663213}, issn = {1613-3560}, mesh = {Defecation ; Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome ; }, }
@article {pmid29659775, year = {2018}, author = {Peter, J and Zeitz, J and Stallmach, A}, title = {Ustekinumab Rescue Therapy in a Patient With Chronic Refractory Pouchitis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {12}, number = {8}, pages = {1008-1009}, doi = {10.1093/ecco-jcc/jjy037}, pmid = {29659775}, issn = {1876-4479}, mesh = {Adult ; Anti-Inflammatory Agents/administration &amp; dosage ; Colitis, Ulcerative/diagnosis/surgery ; Crohn Disease/*diagnosis ; Diagnosis, Differential ; Drug Resistance, Multiple ; Endoscopy, Gastrointestinal/methods ; Fecal Microbiota Transplantation/*adverse effects/methods ; Humans ; *Intestinal Mucosa/diagnostic imaging/pathology ; Male ; Patient Care Management/methods ; *Pouchitis/diagnosis/etiology/physiopathology/therapy ; Prednisolone/*administration &amp; dosage ; Proctocolectomy, Restorative/*adverse effects/methods ; Recurrence ; Severity of Illness Index ; Treatment Outcome ; Ustekinumab/*administration &amp; dosage ; }, }
@article {pmid29654837, year = {2018}, author = {Seekatz, AM and Theriot, CM and Rao, K and Chang, YM and Freeman, AE and Kao, JY and Young, VB}, title = {Restoration of short chain fatty acid and bile acid metabolism following fecal microbiota transplantation in patients with recurrent Clostridium difficile infection.}, journal = {Anaerobe}, volume = {53}, number = {}, pages = {64-73}, pmid = {29654837}, issn = {1095-8274}, support = {UL1 TR000433/TR/NCATS NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; R21 AI120599/AI/NIAID NIH HHS/United States ; K01 GM109236/GM/NIGMS NIH HHS/United States ; P30 AG024824/AG/NIA NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; R35 GM119438/GM/NIGMS NIH HHS/United States ; U24 DK097153/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bile Acids and Salts/*metabolism ; Clostridium Infections/*therapy ; Fatty Acids, Volatile/*metabolism ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Male ; Metabolomics ; Middle Aged ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Secondary Prevention/*methods ; Sequence Analysis, DNA ; Young Adult ; }, abstract = {A significant proportion of individuals develop recurrent Clostridium difficile infection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery. One of the proposed functions associated with restoration of colonization resistance against C. difficile has been recovery of bile acid metabolism. In this study, we aimed to assess recovery of short chain fatty acids (SCFAs) in addition to bile acids alongside microbial community structure in six patients with recurrent CDI following treatment with FMT over time. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Sustained increases in the levels of the SCFAs butyrate, acetate, and propionate were observed post-FMT, and variable recovery over time was observed in the secondary bile acids deoxycholate and lithocholate. To correlate these changes with specific microbial taxa at an individual level, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Metabolites that increased following FMT were associated with bacteria classified within the Lachnospiraceae, Ruminococcaceae, and unclassified Clostridiales families. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT.}, }
@article {pmid29653191, year = {2018}, author = {Vila, J}, title = {Microbiota transplantation and/or CRISPR/Cas in the battle against antimicrobial resistance.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {24}, number = {7}, pages = {684-686}, doi = {10.1016/j.cmi.2018.03.043}, pmid = {29653191}, issn = {1469-0691}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacteria/*genetics ; Bacterial Infections/*microbiology/*therapy ; *CRISPR-Cas Systems ; *Drug Resistance, Bacterial ; Drug Resistance, Multiple, Bacterial ; Enterobacteriaceae/genetics ; Enterobacteriaceae Infections/microbiology/therapy ; *Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Treatment Outcome ; }, }
@article {pmid29652112, year = {2018}, author = {Pagano, C and Vergani, C and Invernizzi, C and Bussone, M and Benegiamo, G and Venturi, M}, title = {Mucopexy-recto anal lifting: a standardized minimally invasive method of managing symptomatic hemorrhoids, with an innovative suturing technique and the HemorPex System®.}, journal = {Minerva chirurgica}, volume = {73}, number = {5}, pages = {469-474}, doi = {10.23736/S0026-4733.18.07425-4}, pmid = {29652112}, issn = {1827-1626}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anal Canal/surgery ; Equipment Design ; Female ; Hemorrhoidectomy/*instrumentation/*methods ; Hemorrhoids/diagnosis/*surgery ; Humans ; Intestinal Mucosa/surgery ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; *Proctoscopes ; *Suture Techniques ; }, abstract = {BACKGROUND: Conservative surgery of hemorrhoidal disease is less painful than traditional hemorrhoidectomy, and mucopexy has less risk of serious postoperative complications than stapled hemorrhoidopexy. The aim of this study was to evaluate the safety and effectiveness of a standardized, modified hemorrhoidopexy, named Mucopexy-Recto Anal Lifting (MuRAL) with the HemorPex System (HPS) in patients with symptomatic III and IV degree hemorrhoids.<br><br>METHODS: Patients were enrolled from May 2013 to Dec 2015 and operated on with the MuRAL technique, based on arterial ligation and mucopexy at 6 locations, using a standardized clockwise/anti-clockwise rotation sequence of the HPS anoscope. Follow-up controls were carried out by independent observers, as follows: a digital exploration 3 weeks after the intervention, digital exploration plus proctoscopy at 3 and 12 months and repeated at a 12 months interval. Patients who did not strictly follow the postoperative controls were excluded from the study. Primary outcome measurement was the recurrence rate. Secondary measurements were: operative time, hospital stay, postoperative pain, postoperative symptoms and satisfaction score.<br><br>RESULTS: We operated on 126 patients (72 males, mean age 53.9, range 29-83): 87 (69.6%) with III degree and 39 with IV degree hemorrhoids; 13 patients had a MuRAL as a revisional procedure of a previous operation for hemorrhoids. Mean duration of follow-up was 554 days (range 281-1219). Four patients were excluded from the study. One-year recurrence rate was 4.1%. The mean duration of the intervention was 29.5 minutes (range 23-60) and 92 patients (73%) were discharged during the same day of the operation. Pain VAS Score in the first, second and third postoperative day was 3.9, 2.5, and 1.9, respectively. Twenty-two patients (18%), all submitted to spinal anesthesia, had postoperative acute urinary retention. Fecal urgency, observed in 18.8% of patients at the first control, disappeared within one year after the operation. Mean time to return to normal activity was 8 days (range 5 -10). The patient satisfaction scores at one-year follow up were 31.1% excellent, 57.4% good, 7.4% fairly good and 4.1% poor. In patients with III degree hemorrhoids operative time was significantly shorter, postoperative pain better and transient fecal urgency lower than in IV degree patients. In our experience the standardization of MuRAL operation with HPS, turned out to be a safe and effective minimally invasive approach in managing symptomatic III and IV degree hemorrhoids, avoiding the risk of severe complications, with the possibility to perform a redo-MuRAL in the event of recurrence.<br><br>CONCLUSIONS: In our series up to 88% of the patients reported a good, or excellent one-year satisfaction score. Further comparative randomized studies with longer follow-up period are needed.}, }
@article {pmid29651860, year = {2018}, author = {Vigvári, S and Sipos, D and Kappéter, &#xc1; and Feiszt, Z and Kovács, B and Péterfi, Z}, title = {Risk factors for Clostridium difficile infections in Baranya County, Southern Hungary.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {65}, number = {2}, pages = {183-192}, doi = {10.1556/030.65.2018.023}, pmid = {29651860}, issn = {1217-8950}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Case-Control Studies ; *Clostridioides difficile ; Clostridium Infections/*drug therapy/epidemiology/*microbiology ; Female ; Humans ; Hungary/epidemiology ; Male ; Middle Aged ; Odds Ratio ; Risk Factors ; Time Factors ; }, abstract = {In the past decade, Clostridium difficile infections (CDIs) have become a major public health challenge. Their epidemiology has radically changed with a significant rise in the number of cases and an increase in severe episodes. Recurrence and failure of conventional treatments are very common. Furthermore, a spread of CDI has emerged in general population without the usual risk factors (unexposed to antibiotic treatment, young people, etc.). The conventional treatments (metronidazole and vancomycin) are still effective and are the first-line antibiotics with new recommendations. New therapeutic strategies are now available. Recent studies show a better efficacy of vancomycin compared with metronidazole for severe episodes. Fidaxomicin is a novel antibiotic drug with an efficacy similar to vancomycin and a lower risk of recurrence. Finally, for relapsing forms, fecal microbiota transplantation (FMT) seems to be the best option. We determined risk factors for CDI among patients treated at the infectious diseases ward of our hospital in Pécs. The study included 886 patients with CDI from 2009 to 2014. The average number of recurrent episodes was 2.16 and the proportion of severe cases was 66%. Among our patients, 726 (82%) had taken antibiotics and 769 (86.8%) had been hospitalized in the prior 3 months before developing CDI. We have found that prior statin use could be a significant risk factor of CDI (OR: 1.7765, 95% CI: 1.3966-2.2597, p < 0.0001). Finally, we present the comparative efficacy of different types of treatment (metronidazole, vancomycin, fidaxomicin, and FMT).}, }
@article {pmid29644492, year = {2018}, author = {Kornerup, LS and Gluud, LL and Vilstrup, H and Dam, G}, title = {Update on the Therapeutic Management of Hepatic Encephalopathy.}, journal = {Current gastroenterology reports}, volume = {20}, number = {5}, pages = {21}, pmid = {29644492}, issn = {1534-312X}, mesh = {Amino Acids, Branched-Chain/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Disease Management ; Fecal Microbiota Transplantation ; Gastrointestinal Agents/*therapeutic use ; Hepatic Encephalopathy/*drug therapy/therapy ; Humans ; Lactulose/therapeutic use ; Probiotics/therapeutic use ; Rifamycins/therapeutic use ; Rifaximin ; }, abstract = {PURPOSE OF REVIEW: Hepatic encephalopathy (HE) is a common and devastating complication to chronic liver disease. In this paper, we summarize the latest research and evidence of both conventional and up-coming treatments.<br><br>RECENT FINDINGS: Meta-analyses report beneficial effects of lactulose, branched-chain amino acids, rifaximin, and to some degree L-ornithine L-aspartate on the manifestations of HE in patients with cirrhosis, and generally the numbers needed to treat are low. Recent studies on newer HE treatments including ornithine phenylacetate, spherical carbon, and fecal microbiota transplant also report potentially beneficial effects on HE manifestations. The conventional treatments benefit patients with HE. Newer treatments are under study and more research is needed for their validation.}, }
@article {pmid29637938, year = {2018}, author = {Holleran, G and Scaldaferri, F and Ianiro, G and Lopetuso, L and Mc Namara, D and Mele, MC and Gasbarrini, A and Cammarota, G}, title = {Fecal microbiota transplantation for the treatment of patients with ulcerative colitis and other gastrointestinal conditions beyond Clostridium difficile infection: an update.}, journal = {Drugs of today (Barcelona, Spain : 1998)}, volume = {54}, number = {2}, pages = {123-136}, doi = {10.1358/dot.2018.54.2.2760765}, pmid = {29637938}, issn = {1699-3993}, mesh = {Clostridium Infections/microbiology/therapy ; Colitis, Ulcerative/microbiology/*therapy ; Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Inflammatory Bowel Diseases/microbiology/therapy ; Intestinal Diseases/microbiology/*therapy ; }, abstract = {Fecal microbiota transplantation (FMT) is the transplantation of microbial gut contents from a healthy individual into the gastrointestinal tract of a person with a disease, with a view to increasing the recipient's gut microbial diversity and bacterial richness and restoring microbial homeostasis. FMT has been proven to be a safe and effective treatment for Clostridium difficile infection (CDI) and it is now a recommended treatment for recurrent or refractory infection. FMT is not currently recommended for use outside of CDI due to concerns regarding outcome and safety; however, several case series and randomized controlled trials have described its use in a research environment for a few gastrointestinal conditions related to intestinal dysbiosis including ulcerative colitis (UC), Crohn's disease (CD) and irritable bowel syndrome (IBS). The most successful reports of the clinical efficacy of FMT in gastrointestinal conditions outside of CDI have been in treating UC. We summarize the current literature regarding the use of FMT in UC, including methodology, clinical efficacy and safety concerns, and identify pitfalls and areas for future development. We also describe the available evidence to date on the use of FMT in CD, IBS and other conditions related to intestinal dysbiosi.}, }
@article {pmid29635868, year = {2018}, author = {Soontararak, S and Chow, L and Johnson, V and Coy, J and Wheat, W and Regan, D and Dow, S}, title = {Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose-Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model.}, journal = {Stem cells translational medicine}, volume = {7}, number = {6}, pages = {456-467}, pmid = {29635868}, issn = {2157-6564}, support = {K01 OD022982/OD/NIH HHS/United States ; P30 CA046934/CA/NCI NIH HHS/United States ; }, mesh = {Adipose Tissue/cytology ; Animals ; Bacteria/genetics/isolation &amp; purification ; Cell- and Tissue-Based Therapy ; Cells, Cultured ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Feces/microbiology ; Female ; Induced Pluripotent Stem Cells/cytology ; Inflammatory Bowel Diseases/chemically induced/pathology/*therapy ; Intestines/microbiology/physiology ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*cytology/metabolism ; Mice ; *Microbiota ; Regeneration ; }, abstract = {Cellular therapy with allogeneic or autologous mesenchymal stem cells (MSC) has emerged as a promising new therapeutic strategy for managing inflammatory bowel disease (IBD). However, MSC therapy ideally requires a convenient and relatively homogenous cell source (typically bone marrow or adipose tissues) and the ability to generate cells with stable phenotype and function. An alternative means of generating allogeneic MSC is to derive them from induced pluripotent stem cells (iPSC), which could in theory provide an indefinite supply of MSC with well-defined phenotype and function. Therefore, we compared the effectiveness of iPSC-derived MSC (iMSC) and adipose-derived MSC (adMSC) in a mouse model of IBD (dextran sodium sulfate-induced colitis), and investigated mechanisms of intestinal protection. We found that iMSC were equivalent to adMSC in terms of significantly improving clinical abnormalities in treated mice and reducing lesion scores and inflammation in the gut. Administration of iMSC also stimulated significant intestinal epithelial cell proliferation, increased in the numbers of Lgr5+ intestinal stem cells, and increased intestinal angiogenesis. In addition, the microbiome alterations present in mice with colitis were partially restored to resemble those of healthy mice following treatment with iMSC or adMSC. Thus, iMSC administration improved overall intestinal health and healing with equivalent potency to treatment with adMSC. This therefore is the first report of the effectiveness of iMSC in the treatment of IBD, along with a description of unique mechanisms of action with respect to intestinal healing and microbiome restoration. Stem Cells Translational Medicine 2018;7:456-467.}, }
@article {pmid29634580, year = {2018}, author = {Danve, A and Deodhar, AA}, title = {Complementary medicine for axial spondyloarthritis: is there any scientific evidence?.}, journal = {Current opinion in rheumatology}, volume = {30}, number = {4}, pages = {310-318}, doi = {10.1097/BOR.0000000000000513}, pmid = {29634580}, issn = {1531-6963}, mesh = {Complementary Therapies ; Humans ; Reproducibility of Results ; Spondylarthritis/*drug therapy ; }, abstract = {PURPOSE OF REVIEW: Majority of patients with axial spondyloarthritis (axSpA) report use of complementary and alternative medicine (CAM) therapies before and even after the diagnosis, due to perceived efficacy and wide-spread belief that these modalities lack side effects. In this review, we describe the available scientific evidence for the CAM therapies in axSpA.<br><br>RECENT FINDINGS: Clinical trials of the CAM therapies in axSpA are generally hampered by small sample size, short duration, difficulties in blinding, lack of control groups and strong placebo effect. Nonetheless, exercise programs like Pilates and mind-body techniques such as Tai Chi may have favorable effect on the disease activity and function. Although not yet confirmed, the modulation of the microbiome with the help of probiotics or fecal transplant has face validity given the evolving scientific rationale. Diet has only limited role in the management of axSpA. Deep tissue massage, omega-3 fatty acids and Stanger bath were found to be useful in small studies. CAM therapies are not always entirely well tolerated, particularly the manipulative techniques like chiropractic and Tui-na in patients with advanced disease and osteoporosis. There are no trials of yoga in axSpA despite the wider acceptance and use of yoga as an effective mind-body technique.<br><br>SUMMARY: Larger and better quality clinical trials of CAM therapies are needed to confirm their efficacy and safety in the management of axSpA and to include them in the 'mainstream' medicine.}, }
@article {pmid29626003, year = {2018}, author = {Axtell, S and Shokoya, A and Yocum, C}, title = {Probable fidaxomicin-induced pancytopenia.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {75}, number = {8}, pages = {532-535}, doi = {10.2146/ajhp170239}, pmid = {29626003}, issn = {1535-2900}, mesh = {Adult ; Anti-Bacterial Agents/administration &amp; dosage/*adverse effects ; Clostridium Infections/drug therapy ; Female ; Fidaxomicin/administration &amp; dosage/*adverse effects ; Humans ; Injections, Subcutaneous ; Pancytopenia/*chemically induced/physiopathology ; }, abstract = {PURPOSE: A case of pancytopenia in a patient receiving treatment with fidaxomicin for Clostridium difficile infection (CDI) is described.<br><br>SUMMARY: A 33-year-old Caucasian woman was admitted to the hospital with a chief complaint of loose stools occurring approximately 7 times a day; she also reported fever, nausea, diffuse abdominal pain, and fatigue. The patient had a history of recurrent CDI, recurrent urinary tract infections, nephrolithiasis, chronic hepatitis C, and endometriosis. Her previous therapies for CDI included metronidazole, vancomycin, rifaximin, and fecal microbiota transplantation. On admission, she had a platelet count of 172,000 platelets/mm[3], hemoglobin concentration of 11.1 g/dL, and white blood cell (WBC) count of 3,100 cells/mm[3]. Within 24 hours of the first dose of fidaxomicin and before the second dose, the patient's platelet count fell to 156,000 platelets/mm[3], her hemoglobin concentration decreased to 9.9 g/dL, and her WBC count fell to 2,600 cells/mm[3]. Values for all 3 tests continued to decrease during the first few days of fidaxomicin therapy. One dose of filgrastim 300 &#x3bc;g was administered subcutaneously on day 6 in response to the pancytopenia, after which the platelet, hemoglobin, and WBC values stabilized for a day and then generally declined. Platelet, hemoglobin, and WBC values returned to normal within 3 days of the patient's last dose of fidaxomicin. Use of the Naranjo et al. adverse drug reaction probability scale indicated a probable association (score of 6) between fidaxomicin and the patient's pancytopenia.<br><br>CONCLUSION: A 33-year-old woman developed pancytopenia during a course of fidaxomicin therapy for CDI. Platelet, hemoglobin, and WBC values returned to normal within 3 days of the final fidaxomicin dose.}, }
@article {pmid29620765, year = {2018}, author = {Willyard, C}, title = {Squeaky clean mice could be ruining research.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {16-18}, pmid = {29620765}, issn = {1476-4687}, mesh = {Adult ; Animals ; Animals, Laboratory/genetics/*immunology/microbiology/virology ; Animals, Wild/*immunology/*microbiology/virology ; Biomedical Research/*methods ; *Disease Models, Animal ; Fecal Microbiota Transplantation/veterinary ; Female ; Gene Expression Profiling ; Germ-Free Life/immunology ; *Housing, Animal ; Humans ; Immunologic Memory/immunology ; Infant ; Listeria monocytogenes/immunology ; Listeriosis/immunology/microbiology/veterinary ; Mice ; Microbiota/immunology ; Pregnancy ; T-Lymphocytes/cytology/immunology ; Yellow Fever Vaccine/administration &amp; dosage/immunology ; }, }
@article {pmid29619403, year = {2018}, author = {Makkawi, S and Camara-Lemarroy, C and Metz, L}, title = {Fecal microbiota transplantation associated with 10 years of stability in a patient with SPMS.}, journal = {Neurology(R) neuroimmunology &amp; neuroinflammation}, volume = {5}, number = {4}, pages = {e459}, pmid = {29619403}, issn = {2332-7812}, }
@article {pmid29617463, year = {2018}, author = {Chassaing, B and Gewirtz, AT}, title = {Mice harboring pathobiont-free microbiota do not develop intestinal inflammation that normally results from an innate immune deficiency.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0195310}, pmid = {29617463}, issn = {1932-6203}, support = {R01 DK083890/DK/NIDDK NIH HHS/United States ; R01 DK099071/DK/NIDDK NIH HHS/United States ; DK083890/NH/NIH HHS/United States ; DK099071/NH/NIH HHS/United States ; }, mesh = {Animals ; Escherichia coli ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Flagellin/metabolism ; Gastroenteritis/*immunology/*microbiology ; Gastrointestinal Microbiome/*immunology ; Immunity, Innate ; Immunologic Deficiency Syndromes/*metabolism/*microbiology ; Intestines/*immunology/*microbiology ; Lipopolysaccharides/metabolism ; Male ; Metabolic Syndrome/immunology/microbiology ; Mice, Inbred C57BL ; Mice, Knockout ; Toll-Like Receptor 5/deficiency/genetics ; }, abstract = {BACKGROUND: Inability to maintain a stable and beneficial microbiota is associated with chronic gut inflammation, which classically manifests as colitis but may more commonly exist as low-grade inflammation that promotes metabolic syndrome. Alterations in microbiota, and associated inflammation, can originate from dysfunction in host proteins that manage the microbiota, such as the flagellin receptor TLR5. That the complete absence of a microbiota (i.e. germfree conditions) eliminates all evidence of inflammation in TLR5-deficient mice demonstrates that this model of gut inflammation is microbiota-dependent. We hypothesize that such microbiota dependency reflects an inability to manage pathobionts, such as Adherent-Invasive E. coli (AIEC). Herein, we examined the extent to which microbiota mismanagement and associated inflammation in TLR5-deficient mice would manifest in a limited and pathobiont-free microbiota. For this purpose, WT and TLR5-deficient mice were generated and maintained with the 8-member consortium of bacteria referred to as "Altered Schaedler Flora" (ASF). Such ASF animals were subsequently inoculated with AIEC reference strain LF82. Feces were assayed for bacterial loads, fecal lipopolysaccharide and flagellin loads, fecal inflammatory marker lipocalin-2 and microbiota composition.<br><br>RESULTS: Relative to similarly maintained WT mice, mice lacking TLR5 (T5KO) did not display low-grade intestinal inflammation nor metabolic syndrome under ASF conditions. Concomitantly, the ASF microbial community was similar between WT and T5KO mice, while inoculation with AIEC strain LF82 resulted in alteration of the ASF community in T5KO mice compared to WT control animals. AIEC LF82 inoculation in ASF T5KO mice resulted in microbiota components having elevated levels of bioactive lipopolysaccharide and flagellin, a modest level of low-grade inflammation and increased adiposity.<br><br>CONCLUSIONS: In a limited-complexity pathobiont-free microbiota, loss of the flagellin receptor TLR5 does not impact microbiota composition nor its ability to promote inflammation. Addition of AIEC to this ecosystem perturbs microbiota composition, increases levels of lipopolysaccharide and flagellin, but only modestly promotes gut inflammation and adiposity, suggesting that the phenotypes previously associated with loss of this innate immune receptor require disruption of complex microbiota.}, }
@article {pmid29617178, year = {2018}, author = {Jørgensen, SMD and Erikstrup, C and Dinh, KM and Lemming, LE and Dahlerup, JF and Hvas, CL}, title = {Recruitment of feces donors among blood donors: Results from an observational cohort study.}, journal = {Gut microbes}, volume = {9}, number = {6}, pages = {540-550}, pmid = {29617178}, issn = {1949-0984}, mesh = {Adult ; Blood/microbiology/parasitology/virology ; Blood Chemical Analysis ; Blood Donors/psychology/*statistics &amp; numerical data ; Cohort Studies ; Denmark ; Donor Selection/*statistics &amp; numerical data ; *Feces/microbiology/parasitology/virology ; Female ; Humans ; Male ; Middle Aged ; Surveys and Questionnaires ; }, abstract = {As the use of fecal microbiota transplantation (FMT) has gained momentum, an increasing need for continuous access to healthy feces donors has developed. Blood donors constitute a healthy subset of the general population and may serve as an appropriate group for recruitment. In this study, we investigated the suitability of blood donors as feces donors. In a prospective cohort study, we recruited blood donors onsite at a public Danish blood bank. Following their consent, the blood donors underwent a stepwise screening process: First, blood donors completed an electronic pre-screening questionnaire to rule out predisposing risk factors. Second, eligible blood donors had blood and fecal samples examined. Of 155 blood donors asked to participate, 137 (88%) completed the electronic pre-screening questionnaire, 16 declined, and 2 were excluded. Of the 137 donors who completed the questionnaire, 79 (58%) were excluded mainly due to having an allergy, being overweight, or presenting gastrointestinal complaints. Among the remaining 58 (37%) donors, complete blood and feces screenings were obtained from 46 (79%). Of these 46 donors, 15 (33%) were excluded primarily due to abnormal blood results or the presence of apathogenic intestinal parasites. Overall, 31 (20%; 95% confidence interval 14-27%) of the 155 blood donors qualified as feces donors. In conclusion, blood donors constitute a suitable and motivated population for a continuous recruitment of voluntary feces donors. We found that a stepwise recruitment procedure was feasible and that 20% of the blood donors were eligible for feces donation.}, }
@article {pmid29614305, year = {2018}, author = {Biancheri, P and Divekar, D and Watson, AJM}, title = {Could Fecal Transplantation Become Part of PD-1-Based Immunotherapy, Due to Effects of the Intestinal Microbiome?.}, journal = {Gastroenterology}, volume = {154}, number = {6}, pages = {1845-1847}, doi = {10.1053/j.gastro.2018.03.060}, pmid = {29614305}, issn = {1528-0012}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy ; *Neoplasms, Glandular and Epithelial ; Programmed Cell Death 1 Receptor ; }, }
@article {pmid29607440, year = {2018}, author = {Heath, RD and Cockerell, C and Mankoo, R and Ibdah, JA and Tahan, V}, title = {Fecal microbiota transplantation and its potential therapeutic uses in gastrointestinal disorders.}, journal = {Northern clinics of Istanbul}, volume = {5}, number = {1}, pages = {79-88}, pmid = {29607440}, issn = {2536-4553}, abstract = {Typical human gut flora has been well characterized in previous studies and has been noted to have significant differences when compared with the typical microbiome of various disease states involving the gastrointestinal tract. Such diseases include Clostridium difficile colitis, inflammatory bowel disease, functional bowel syndromes, and various states of liver disease. A growing number of studies have investigated the use of a fecal microbiota transplant as a potential therapy for these disease states.}, }
@article {pmid29606940, year = {2018}, author = {Schneider, KM and Wirtz, TH and Kroy, D and Albers, S and Neumann, UP and Strowig, T and Sellge, G and Trautwein, C}, title = {Successful Fecal Microbiota Transplantation in a Patient with Severe Complicated Clostridium difficile Infection after Liver Transplantation.}, journal = {Case reports in gastroenterology}, volume = {12}, number = {1}, pages = {76-84}, pmid = {29606940}, issn = {1662-0631}, abstract = {Clostridium difficile infection (CDI) represents one of the most common healthcare-associated infections. Due to increasing numbers of recurrences and therapy failures, CDI has become a major disease burden. Studies have shown that fecal microbiota transplantation (FMT) can both be a safe and highly efficacious therapy for patients with therapy-refractory CDI. However, patients undergoing solid organ transplantation are at high risk for CDI due to long-term immunosuppression, previous antibiotic therapy, and proton pump inhibitor use. Additionally, these patients may be especially prone to adverse events related to FMT. Here, we report a successful FMT in a patient with severe therapy-refractory CDI after liver transplantation.}, }
@article {pmid29605414, year = {2018}, author = {Syal, G and Kashani, A and Shih, DQ}, title = {Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Primer for Internists.}, journal = {The American journal of medicine}, volume = {131}, number = {9}, pages = {1017-1024}, doi = {10.1016/j.amjmed.2018.03.010}, pmid = {29605414}, issn = {1555-7162}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; Enterocolitis, Pseudomembranous/complications/therapy ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Premedication ; Severity of Illness Index ; Specimen Handling ; }, abstract = {Inflammatory bowel disease consists of disorders characterized by chronic idiopathic bowel inflammation. The concept of host-gut-microbiome interaction in the pathogenesis of various complex immune-mediated chronic diseases, including inflammatory bowel disease, has recently generated immense interest. Mounting evidence confirms alteration of intestinal microflora in patients with inflammatory bowel disease. Thus, restoration of normal gut microbiota has become a focus of basic and clinical research in recent years. Fecal microbiota transplantation is being explored as one such therapeutic strategy and has shown encouraging results in the management of patients with inflammatory bowel disease.}, }
@article {pmid29601470, year = {2018}, author = {Wang, G and Feuerbacher, LA and Hardwidge, PR}, title = {Influence of Intestinal Microbiota Transplantation and NleH Expression on Citrobacter rodentium Colonization of Mice.}, journal = {Pathogens (Basel, Switzerland)}, volume = {7}, number = {2}, pages = {}, pmid = {29601470}, issn = {2076-0817}, support = {R01 AI099002/AI/NIAID NIH HHS/United States ; R56 AI099002/AI/NIAID NIH HHS/United States ; }, abstract = {The intestinal microbiota plays an important role in regulating host resistance to enteric pathogens. The relative abundance of the microbiota is dependent upon both genetic and environmental factors. The attaching and effacing pathogens enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and Citrobacter rodentium cause diarrheal disease and translocate type III secretion system effector proteins into host cells to inhibit pro-inflammatory host responses. Here we determined the influence of both the intestinal microbiota and the expression of the C. rodentium NleH effector on C. rodentium colonization in different mouse models. We performed fecal transplantation experiments between C57BL/6J and C57BL/10ScNJ mice and found that such microbiota transfers altered both the host resistance to C. rodentium infection as well as the benefit or detriment of expressing NleH to C. rodentium intestinal colonization.}, }
@article {pmid29601446, year = {2019}, author = {Aldrich, AM and Argo, T and Koehler, TJ and Olivero, R}, title = {Analysis of Treatment Outcomes for Recurrent Clostridium difficile Infections and Fecal Microbiota Transplantation in a Pediatric Hospital.}, journal = {The Pediatric infectious disease journal}, volume = {38}, number = {1}, pages = {32-36}, doi = {10.1097/INF.0000000000002053}, pmid = {29601446}, issn = {1532-0987}, mesh = {Adolescent ; Anti-Bacterial Agents/therapeutic use ; Child ; Child, Preschool ; Clostridioides difficile/drug effects ; Clostridium Infections/*therapy ; Diarrhea/microbiology ; *Fecal Microbiota Transplantation ; Female ; *Hospitals, Pediatric ; Humans ; Infant ; Male ; Recurrence ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is one of the most common nosocomial infections in the United States, with an increasing incidence in children. Approximately 20% of pediatric patients develop recurrent infections. It's imperative to further analyze the incidence of recurrent CDI in the pediatric population and determine the most effective treatments. The primary goal of this study is to characterize children with recurrent CDI at our institution, including both hospital-acquired CDI (HA-CDI) and community-acquired CDI (CA-CDI) cases, summarize the various treatments utilized, including fecal microbiota transplant (FMT) and compare their success rates.<br><br>METHODS: A retrospective cohort study of pediatric patients 1-21 years of age treated for CDI at a single institution from January 2010 to December 2014 was performed.<br><br>RESULTS: There were 175 subjects with 215 separate episodes of CDI. Oral metronidazole was the most common initial treatment (145/207, 70%) followed by oral vancomycin (30/207, 15%), with recurrence rates of 30% (42/145) and 37% (11/30), respectively. Twenty-nine percent (63/215) of all initial CDI cases had at least 1 documented recurrence. Using multivariate analysis, subjects with HA-CDI were 2.6 times less likely to recur than those with CA-CDI (odds ratio: 0.39; 95% confidence interval: 0.18-0.85; P = 0.018). The overall success rate for FMT at our institution was 10/12 (83%).<br><br>CONCLUSIONS: Our data show that cases of HA-CDI were less likely to recur compared with CA-CDI. Although currently reserved for multiply-recurrent cases, FMT was highly successful in our small cohort. More studies on FMT should be conducted to further evaluate its usefulness in the treatment of recurrent CDI in children.}, }
@article {pmid29600698, year = {2018}, author = {Campion, D and Ponzo, P and Alessandria, C and Saracco, GM and Balzola, F}, title = {The role of microbiota in autism spectrum disorders.}, journal = {Minerva gastroenterologica e dietologica}, volume = {64}, number = {4}, pages = {333-350}, doi = {10.23736/S1121-421X.18.02493-5}, pmid = {29600698}, issn = {1827-1642}, mesh = {Autism Spectrum Disorder/*microbiology/therapy ; Dysbiosis ; Humans ; *Microbiota ; }, abstract = {Autism spectrum disorder (ASD) defines a set of neurodevelopmental disorders characterized by persistent deficits in social communication and interaction, along with repetitive patterns of behavior. Symptoms generally appear in the early developmental period and cause significant impairment in individual and social functioning. In recent years the increased prevalence of ASD, along with the evidence of a significant link between autism and gastrointestinal (GI) disturbances, raised a special interest in exploring the reciprocal influences between gut and brain. Investigators highlighted the existence of a so-called "gut-brain axis," empowering the hypothesis that GI abnormalities could trigger neuropsychiatric symptoms in ASD. Intestinal microbiota is thought to play a pivotal role in gut and systemic homeostasis, in central nervous system development, as well as in behavioral modulation and recurrent microbial imbalances have been shown in gut microbiota of autistic people. In this review we analyze current knowledge about intestinal microbiota and the relevance and role of dysbiosis in ASD. The most accredited theories about gut-brain interaction will be reviewed, along with current scientific evidence supporting the relationship between microbial imbalances and impairment of neurodevelopment. Finally, we will focus on the results of different therapeutic approaches in this context: administration of pre- and probiotics, antibiotics, fecal microbiota transplantation and special diets and dietary supplements.}, }
@article {pmid29600252, year = {2018}, author = {Hota, SS and Poutanen, SM}, title = {Is a Single Fecal Microbiota Transplant a Promising Treatment for Recurrent Clostridium difficile Infection?.}, journal = {Open forum infectious diseases}, volume = {5}, number = {3}, pages = {ofy045}, pmid = {29600252}, issn = {2328-8957}, abstract = {Clostridium difficile infection, a common hospital-associated infection, is a gastrointestinal illness that becomes recurrent in about 25% of infected patients. Fecal microbiota transplantation (FMT) is increasingly supported by clinical trials as an effective treatment for recurrent Clostridium difficile infection, but a number of questions remain about how it can be optimally performed. In this Perspective, we discuss controversies in FMT methodologies and reporting within randomized controlled trials, all of which may influence clinical outcomes in treated patients. Finally, we focus on the question of whether single vs multiple FMTs are necessary to achieve favorable outcomes for the treatment of recurrent Clostridium difficile infection, postulating on why there may be an association between number of FMTs and clinical effectiveness.}, }
@article {pmid29599513, year = {2019}, author = {Stoll, ML and Pierce, MK and Watkins, JA and Zhang, M and Weiss, PF and Weiss, JE and Elson, CO and Cron, RQ and Kumar, R and Morrow, CD and Schoeb, TR}, title = {Akkermansia muciniphila is permissive to arthritis in the K/BxN mouse model of arthritis.}, journal = {Genes and immunity}, volume = {20}, number = {2}, pages = {158-166}, pmid = {29599513}, issn = {1476-5470}, support = {UL1 TR003096/TR/NCATS NIH HHS/United States ; P30 AR050948/AR/NIAMS NIH HHS/United States ; UL1 TR001417/TR/NCATS NIH HHS/United States ; P60 AR064172/AR/NIAMS NIH HHS/United States ; R21 ES024413/ES/NIEHS NIH HHS/United States ; }, mesh = {Adolescent ; Animals ; Ankle/pathology ; Arthritis/*microbiology ; Bacteroides/isolation &amp; purification/pathogenicity ; Child ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred NOD ; Verrucomicrobia/isolation &amp; purification/pathogenicity ; }, abstract = {Studies have identified abnormalities in the microbiota of patients with arthritis. To evaluate the pathogenicity of human microbiota, we performed fecal microbial transplantation from children with spondyloarthritis and controls to germ-free KRN/B6xNOD mice. Ankle swelling was equivalent in those that received patient vs. control microbiota. Principal coordinates analysis revealed incomplete uptake of the human microbiota with over-representation of two genera (Bacteroides and Akkermansia) among the transplanted mice. The microbiota predicted the extent of ankle swelling (R2 = 0.185, p = 0.018). The abundances of Bacteroides (r = -0.510, p = 0.010) inversely and Akkermansia (r = 0.367, p = 0.078) directly correlated with ankle swelling. Addition of Akkermansia muciniphila to Altered Schaedler's Flora (ASF) resulted in small but statistically significant increased ankle swelling as compared to mice that received ASF alone (4.0 mm, 3.9-4.1 vs. 3.9 mm, IQR 3.6-4.0, p = 0.041), as did addition of A. muciniphila cultures to transplanted human microbiota as compared to mice that received transplanted human microbiota alone (4.5 mm, IQR 4.3-5.5 vs. 4.1 mm, IQR 3.9-4.3, p = 0.019). This study supports previous findings of an association between A. muciniphila and arthritis.}, }
@article {pmid29595013, year = {2018}, author = {Cambier, A and Giot, JB and Leonard, P and Bletard, N and Meunier, P and Hustinx, R and Delwaide, J and Meurisse, N and Honore, P and Losson, B and Hayette, MP and Detry, O}, title = {[Multidisciplinary management of alveolar echinococcosis : Echino-Liege Working Group].}, journal = {Revue medicale de Liege}, volume = {73}, number = {3}, pages = {135-142}, pmid = {29595013}, issn = {0370-629X}, mesh = {Albendazole/therapeutic use ; Animals ; Anthelmintics/therapeutic use ; DNA, Protozoan ; Diagnostic Imaging ; Echinococcosis/*diagnosis/*therapy/transmission ; Echinococcus multilocularis/genetics ; Humans ; Liver Transplantation ; Patient Care Team ; Polymerase Chain Reaction ; }, abstract = {Alveolar echinococcosis is a zoonotic disease due to the tapeworm Echinococcus multilocularis. The definitive host is the red fox. Until recently, Belgium was considered a country at very low risk for alveolar echinococcosis. However, recent studies carried out in southern Belgium have revealed, through post-mortem examination, high prevalences (up to 62 %) in foxes. Cats and dogs can act as definitive hosts. Human are accidentally infected by ingestion of food contaminated by the feces. After a long incubation period, invasive hepatic lesions may appear, as well as extra-hepatic lesions. The disease may be fatal. The diagnosis is based on imaging techniques, serology and nucleic acid detection in tissues. Early diagnosis may allow surgical removal of the lesion associated with at least 2 years of albendazole postoperative treatment. In case of contraindication to surgery, a long term treatment with albendazole is necessary. Liver transplantation is sometimes necessary. This article presents the epidemiologic, clinical, diagnostic and therapeutics features of this zoonotic disease.}, }
@article {pmid29594746, year = {2018}, author = {Panchal, P and Budree, S and Scheeler, A and Medina, G and Seng, M and Wong, WF and Elliott, R and Eliott, R and Mitchell, T and Kassam, Z and Allegretti, JR and Osman, M}, title = {Scaling Safe Access to Fecal Microbiota Transplantation: Past, Present, and Future.}, journal = {Current gastroenterology reports}, volume = {20}, number = {4}, pages = {14}, pmid = {29594746}, issn = {1534-312X}, mesh = {Clostridium Infections/therapy ; Donor Selection/methods ; Fecal Microbiota Transplantation/methods/*trends ; Gastrointestinal Microbiome ; Health Services Accessibility/organization &amp; administration/*trends ; Humans ; Tissue Banks/organization &amp; administration/*trends ; }, abstract = {PURPOSE OF REVIEW: Universal stool banks (USBs) have emerged as a potential model for scaling access to fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI). In this review, we outline the historical barriers constraining access to FMT, the evidence on methods and outcomes of USBs, and potential future directions for expanding access.<br><br>RECENT FINDINGS: Key historical barriers to FMT access include regulatory uncertainty, operational complexity of sourcing screened donor material, and logistical challenges of delivering fresh treatment preparations. USBs have demonstrated that FMT can be delivered safely at scale by centralizing donor selection, material processing, and safety monitoring. More evidence is needed to optimize USB methods, including for donor screening, material processing, and novel delivery modalities. USBs have catalyzed broad access to FMT in North America and Europe. Future directions include developing evidence regarding oral preparations, harmonizing guidelines, disseminating best practice protocols, establishing long-term safety profiles, and expanding access to geographic areas of unmet need.}, }
@article {pmid29592876, year = {2018}, author = {DeFilipp, Z and Peled, JU and Li, S and Mahabamunuge, J and Dagher, Z and Slingerland, AE and Del Rio, C and Valles, B and Kempner, ME and Smith, M and Brown, J and Dey, BR and El-Jawahri, A and McAfee, SL and Spitzer, TR and Ballen, KK and Sung, AD and Dalton, TE and Messina, JA and Dettmer, K and Liebisch, G and Oefner, P and Taur, Y and Pamer, EG and Holler, E and Mansour, MK and van den Brink, MRM and Hohmann, E and Jenq, RR and Chen, YB}, title = {Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity.}, journal = {Blood advances}, volume = {2}, number = {7}, pages = {745-753}, pmid = {29592876}, issn = {2473-9537}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K08 AI110655/AI/NIAID NIH HHS/United States ; KL2 TR001115/TR/NCATS NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; T32 AI100851/AI/NIAID NIH HHS/United States ; S10 OD018164/OD/NIH HHS/United States ; }, mesh = {Adult ; Aged ; Allografts ; Bacteremia/etiology ; Fecal Microbiota Transplantation/*methods/mortality ; Female ; Gastrointestinal Tract/pathology ; Graft vs Host Disease/etiology/pathology ; Hematopoietic Stem Cell Transplantation/*methods ; Humans ; Male ; Microbiota/genetics ; Middle Aged ; Pilot Projects ; Survival Analysis ; }, abstract = {We hypothesized that third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT). In this open-label single-group pilot study, 18 subjects were enrolled before allo-HCT and planned to receive third-party FMT capsules. FMT capsules were administered no later than 4 weeks after neutrophil engraftment, and antibiotics were not allowed within 48 hours before FMT. Five patients did not receive FMT because of the development of early acute gastrointestinal (GI) graft-versus-host disease (GVHD) before FMT (n = 3), persistent HCT-associated GI toxicity (n = 1), or patient decision (n = 1). Thirteen patients received FMT at a median of 27 days (range, 19-45 days) after HCT. Participants were able to swallow and tolerate all FMT capsules, meeting the primary study endpoint of feasibility. FMT was tolerated well, with 1 treatment-related significant adverse event (abdominal pain). Two patients subsequently developed acute GI GVHD, with 1 patient also having concurrent bacteremia. No additional cases of bacteremia occurred. Median follow-up for survivors is 15 months (range, 13-20 months). The Kaplan-Meier estimates for 12-month overall survival and progression-free survival after FMT were 85% (95% confidence interval, 51%-96%) and 85% (95% confidence interval, 51%-96%), respectively. There was 1 nonrelapse death resulting from acute GI GVHD (12-month nonrelapse mortality, 8%; 95% confidence interval, 0%-30%). Analysis of stool composition and urine 3-indoxyl sulfate concentration indicated improvement in intestinal microbiome diversity after FMT that was associated with expansion of stool-donor taxa. These results indicate that empiric third-party FMT after allo-HCT appears to be feasible, safe, and associated with expansion of recipient microbiome diversity. This trial was registered at www.clinicaltrials.gov as #NCT02733744.}, }
@article {pmid29588334, year = {2019}, author = {Tominaga, K and Tsuchiya, A and Yokoyama, J and Terai, S}, title = {How do you treat this diversion ileitis and pouchitis?.}, journal = {Gut}, volume = {68}, number = {4}, pages = {593-758}, doi = {10.1136/gutjnl-2017-315591}, pmid = {29588334}, issn = {1468-3288}, mesh = {Adult ; Colitis, Ulcerative/surgery ; *Fecal Microbiota Transplantation ; Female ; Humans ; Ileitis/diagnosis/*therapy ; Pouchitis/diagnosis/*therapy ; *Proctocolectomy, Restorative ; Skin Ulcer/surgery ; }, }
@article {pmid29582793, year = {2018}, author = {Chandra, A and Singh, P and Kumar, S and Chopra, N and Gupta, V and Joshi, P and Gupta, V}, title = {Laparoscopic ventral rectopexy: A viable option in procidentia with redundant sigmoid - An Indian perspective.}, journal = {Journal of minimal access surgery}, volume = {14}, number = {4}, pages = {304-310}, pmid = {29582793}, issn = {0972-9941}, abstract = {INTRODUCTION: Laparoscopic ventral mesh rectopexy (LVMR) has gained widespread acceptance for the management of complete rectal prolapse (CRP). However, there have been concerns considering its use in patients with a redundant sigmoid colon. This study was conducted to evaluate the anatomical and functional results following LVMR, particularly in cases of CRP with a redundant sigmoid colon.<br><br>MATERIALS AND METHODS: Retrospective analysis of 25 patients who underwent LVMR from January 2011 to September 2016 was performed. Patients were divided into two groups according to the duration of follow-up. Group A (long-term) with follow-up >3 years and Group B (mid-term) <3 years.<br><br>RESULTS: The study included 25 patients (M:F = 1.5:1) with a median age of 38 years. Eighty-eight percent of the patients had a redundant sigmoid colon. Significant improvement in post-operative Wexner score as compared to pre-operative values was seen in patients with pre-existing constipation (P < 0.0001). In patients presenting with faecal incontinence (FI), significant improvement in post-operative St. Mark's incontinence score was observed. Functional outcomes remain consistent in long-term follow-up (>3 years).<br><br>CONCLUSIONS: LVMR seems to be a feasible surgical procedure with minimum morbidity and good long-term functional outcomes. It provides satisfactory results in patients with redundant sigmoid colon and improves pre-existing constipation and FI.}, }
@article {pmid29582768, year = {2018}, author = {Mushtaq, A}, title = {New clinical recommendations for Clostridium difficile.}, journal = {The Lancet. Infectious diseases}, volume = {18}, number = {4}, pages = {384}, doi = {10.1016/S1473-3099(18)30180-4}, pmid = {29582768}, issn = {1474-4457}, mesh = {Clostridium Infections/*diagnosis/prevention &amp; control/*therapy ; Diagnostic Tests, Routine/methods ; *Disease Management ; Drug Therapy/methods ; Fecal Microbiota Transplantation/methods ; Humans ; Infection Control/methods ; Practice Guidelines as Topic ; United States ; }, }
@article {pmid29582182, year = {2018}, author = {Wald, A}, title = {Diagnosis and Management of Fecal Incontinence.}, journal = {Current gastroenterology reports}, volume = {20}, number = {3}, pages = {9}, pmid = {29582182}, issn = {1534-312X}, mesh = {Biofeedback, Psychology/methods ; Electric Stimulation Therapy/methods ; Endpoint Determination ; Fecal Incontinence/*diagnosis/*therapy ; Humans ; Laxatives/therapeutic use ; Manometry/methods ; Prostheses and Implants ; Stem Cell Transplantation ; Tibial Nerve/physiopathology ; }, abstract = {PURPOSE OF REVIEW: The purpose of this review is to highlight current and newer therapeutic approaches to treat fecal incontinence in patients who do not respond to conservative measures.<br><br>RECENT FINDINGS: Neurostimulation techniques, injection of bulking agents, and radiofrequency energy delivery to the anal canal have been proposed and tested for fecal incontinence over the last decade. Sacral stimulation is both effective and durable and is now the most popular of the invasive techniques whereas percutaneous tibial stimulation, radiofrequency energy, and bulking agents are either less effective or their evaluation has been handicapped by suboptimal study designs. The precise indications for the new vaginal control device and anal plugs remain to be established. The magnetic anal sphincter is disappointing. Stem cell therapy is a potentially exciting approach, which is in its infancy. There continues to be an unmet need for innovative approaches to patients with fecal incontinence who do not respond to conservative measures. The efficacy of current and future therapies should be assessed using criteria more stringent than has been used in the past to provide a more realistic assessment of meaningful efficacy.}, }
@article {pmid29581220, year = {2018}, author = {Smits, LP and Kootte, RS and Levin, E and Prodan, A and Fuentes, S and Zoetendal, EG and Wang, Z and Levison, BS and Cleophas, MCP and Kemper, EM and Dallinga-Thie, GM and Groen, AK and Joosten, LAB and Netea, MG and Stroes, ESG and de Vos, WM and Hazen, SL and Nieuwdorp, M}, title = {Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.}, journal = {Journal of the American Heart Association}, volume = {7}, number = {7}, pages = {}, pmid = {29581220}, issn = {2047-9980}, support = {R01 DK106000/DK/NIDDK NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R01 HL126827/HL/NHLBI NIH HHS/United States ; P20 HL113452/HL/NHLBI NIH HHS/United States ; R01 HL135920/HL/NHLBI NIH HHS/United States ; R01 HL130819/HL/NHLBI NIH HHS/United States ; 250172/ERC_/European Research Council/International ; 310372/ERC_/European Research Council/International ; }, mesh = {Adult ; Aged ; Bacteria/*metabolism ; Carnitine/metabolism ; Choline/*metabolism ; Cytokines/*metabolism ; *Diet, Vegan ; Double-Blind Method ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Inflammation Mediators/*metabolism ; Male ; Metabolic Syndrome/diagnosis/microbiology/*therapy ; Methylamines/*metabolism ; Middle Aged ; Netherlands ; Pilot Projects ; Time Factors ; Treatment Outcome ; Vasculitis/diagnosis/microbiology/*therapy ; Young Adult ; }, abstract = {BACKGROUND: Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge.<br><br>METHODS AND RESULTS: We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2&#xa0;weeks thereafter, we determined the ability to produce TMAO from d6-choline and d3-carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250&#xa0;mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. [18]F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex&#xa0;vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic [18]F-fluorodeoxyglucose uptake, or ex&#xa0;vivo cytokine production from peripheral blood mononuclear cells.<br><br>CONCLUSIONS: Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation.<br><br>CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR 4338.}, }
@article {pmid29579889, year = {2018}, author = {Tenorio González, E and Robles Díaz, M and Sanjuan Jiménez, R and González Grande, R and Olmedo Martín, RV and Rodrigo López, JM and Jiménez Pérez, M}, title = {Retransplant Due to Fulminant Hepatic Failure From Hepatitis E Virus: A Case Report.}, journal = {Transplantation proceedings}, volume = {50}, number = {2}, pages = {685-686}, doi = {10.1016/j.transproceed.2017.09.059}, pmid = {29579889}, issn = {1873-2623}, mesh = {Adult ; Female ; Hepatitis E/*immunology/virology ; Hepatitis E virus ; Humans ; Immunocompromised Host ; Liver Failure, Acute/*immunology/virology ; *Liver Transplantation ; Reoperation ; }, abstract = {Hepatitis E virus (HEV) usually causes self-limiting acute liver infections from fecal or oral transmission, though other routes of infection exist (vertical transmission, blood transfusion, zoonosis). It may give rise to fulminant hepatic failure in 1% of cases. Cases have recently been reported of chronic infection evolving to cirrhosis in immunosuppressed patients, such as those with a liver or kidney transplant. Nonetheless, development of acute liver failure in these patients is exceptional, with few cases published. We present a case of acute liver failure due to HEV in a liver transplant patient who required a liver retransplant 9 years after receiving the original transplant.}, }
@article {pmid29577087, year = {2018}, author = {McCormack, UM and Curião, T and Wilkinson, T and Metzler-Zebeli, BU and Reyer, H and Ryan, T and Calderon-Diaz, JA and Crispie, F and Cotter, PD and Creevey, CJ and Gardiner, GE and Lawlor, PG}, title = {Fecal Microbiota Transplantation in Gestating Sows and Neonatal Offspring Alters Lifetime Intestinal Microbiota and Growth in Offspring.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, pmid = {29577087}, issn = {2379-5077}, abstract = {Previous studies suggest a link between intestinal microbiota and porcine feed efficiency (FE). Therefore, we investigated whether fecal microbiota transplantation (FMT) in sows and/or neonatal offspring, using inocula derived from highly feed-efficient pigs, could improve offspring FE. Pregnant sows were assigned to control or FMT treatments and the subsequent offspring to control treatment, FMT once (at birth), or FMT four times (between birth and weaning). FMT altered sow fecal and colostrum microbiota compositions and resulted in lighter offspring body weight at 70 and 155 days of age when administered to sows and/or offspring. This was accompanied by FMT-associated changes within the offspring's intestinal microbiota, mostly in the ileum. These included transiently higher fecal bacterial diversity and load and numerous compositional differences at the phylum and genus levels (e.g., Spirochaetes and Bacteroidetes at high relative abundances and mostly members of Clostridia, respectively), as well as differences in the abundances of predicted bacterial pathways. In addition, intestinal morphology was negatively impacted, duodenal gene expression altered, and serum protein and cholesterol concentrations reduced due to FMT in sows and/or offspring. Taken together, the results suggest poorer absorptive capacity and intestinal health, most likely explaining the reduced body weight. An additive effect of FMT in sows and offspring also occurred for some parameters. Although these findings have negative implications for the practical use of the FMT regime used here for improving FE in pigs, they nonetheless demonstrate the enormous impact of early-life intestinal microbiota on the host phenotype. IMPORTANCE Here, for the first time, we investigate FMT as a novel strategy to modulate the porcine intestinal microbiota in an attempt to improve FE in pigs. However, reprogramming the maternal and/or offspring microbiome by using fecal transplants derived from highly feed-efficient pigs did not recapitulate the highly efficient phenotype in the offspring and, in fact, had detrimental effects on lifetime growth. Although these findings may not be wholly attributable to microbiota transplantation, as antibiotic and purgative were also part of the regime in sows, similar effects were also seen in offspring, in which these interventions were not used. Nonetheless, additional work is needed to unravel the effects of each component of the FMT regime and to provide additional mechanistic insights. This may lead to the development of an FMT procedure with practical applications for the improvement of FE in pigs, which could in turn improve the profitability of pig production.}, }
@article {pmid29570556, year = {2018}, author = {Woolfson, JP and Schreiber, RA and Butler, AE and MacFarlane, J and Kaczorowski, J and Masucci, L and Bryan, S and Collet, JP}, title = {Province-wide Biliary Atresia Home Screening Program in British Columbia: Evaluation of First 2 Years.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {66}, number = {6}, pages = {845-849}, doi = {10.1097/MPG.0000000000001950}, pmid = {29570556}, issn = {1536-4801}, mesh = {Biliary Atresia/*diagnosis/economics/surgery ; British Columbia ; Cost-Benefit Analysis ; Feces ; Female ; Health Care Costs ; Humans ; Infant, Newborn ; Male ; Neonatal Screening/economics/*methods ; Portoenterostomy, Hepatic ; Program Evaluation ; Sensitivity and Specificity ; }, abstract = {BACKGROUND AND OBJECTIVES: Biliary atresia (BA), a rare newborn liver disease, is the leading cause of liver-related death in children. Early disease recognition and timely surgical Kasai hepatoportoenterostomy (KP) offers long-term survival without liver transplant. Universal BA screening in Taiwan using infant stool color cards (ISCCs) has proven effectiveness. We report our experience with infant stool color card (ISCC) BA screening in a province-wide program in British Columbia (BC). The objective of this study is to assess program performance and cost from launch April 1, 2014 to March 31, 2016.<br><br>METHODS: ISCCs distributed to families upon maternity ward discharge. Parents were instructed to monitor their infant's stool color for 1 month and contacted the screening center with concerns. The number of live births, ISCC distribution, BA cases, and costs were recorded. Cases with Program screen success had both acholic stool recognition (ISCC screen success) and timely referral for BA.<br><br>RESULTS: All 126 maternity units received ISCCs. Of 87,583 live births there were 6 BA cases. Of the 5 cases with ISCC Screen Success 3 had Program Screen Success. The median KP age in the program screen success and failure groups was 49 (42-52) and 116 (49-184) days, respectively. Program sensitivity was 50%, specificity 99%, positive predictive value 4%, and negative predictive value 99%. A random sample of 1054 charts at BC Children's Hospital found an ISCC distribution rate of 94%. After a phase-in period, the annual program cost was $30,033.82, and the ISCC cost per birth was $0.68.<br><br>CONCLUSIONS: The screening program has high specificity and distribution with low cost. Successful program case identification had earlier age at KP. Program modifications aim to improve sensitivity. Longer-term studies will determine program impact on health outcomes.}, }
@article {pmid29569813, year = {2018}, author = {Kang, JM and Park, KS and Kim, JM and Huh, HJ and Ki, CS and Lee, NY and Yoo, KH and Sung, KW and Koo, HH and Kim, YJ}, title = {Prospective monitoring of adenovirus infection and type analysis after allogeneic hematopoietic cell transplantation: A single-center study in Korea.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {20}, number = {3}, pages = {e12885}, pmid = {29569813}, issn = {1399-3062}, mesh = {Adenovirus Infections, Human/*blood/*epidemiology/urine/virology ; Adenoviruses, Human/classification/*isolation &amp; purification ; Adolescent ; Child ; Child, Preschool ; DNA, Viral/blood ; Feces/virology ; Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation/*adverse effects/statistics &amp; numerical data ; Humans ; Incidence ; Infant ; Lymphocyte Count ; Male ; Prospective Studies ; Republic of Korea/epidemiology ; Transplantation, Homologous/adverse effects/statistics &amp; numerical data ; Viral Load ; Viremia ; }, abstract = {BACKGROUND: Epidemiologic studies of human adenovirus (HAdV) in allogeneic hematopoietic cell transplantation (HCT) recipients have been conducted mostly in European countries where HAdV 2 (species C) has been most prevalent in the community. The main objective of this study was to investigate the epidemiology and the characteristics of HAdV infection in Korean allogeneic HCT recipients (<19 years).<br><br>METHODS: In a prospective study from April 2012 to September 2015, HAdV in blood, urine, and stool specimens were monitored weekly from transplantation to day 100 or after if clinically suspected. HAdV infection was defined as positive HAdV PCR result in any specimens regardless of symptoms.<br><br>RESULTS: A total of 1734 specimens were collected from 57 consecutively enrolled recipients. The cumulative incidence of HAdV infection at day 100, and 1&#xa0;year was 10%, and 20%, and the incidence of viremia was 2% and 6%, respectively. The median onset time from HCT to viremia was 221&#xa0;days (range, 7-596&#xa0;days). All viremia cases were caused by only HAdV 3 (species B), whereas several types were detected in stool. Among patients with HAdV infection, lower absolute lymphocyte counts and extensive chronic graft-vs-host disease were associated with viremia (P&#xa0;=&#xa0;.028 and P&#xa0;=&#xa0;.006, respectively).<br><br>CONCLUSIONS: Compared to western studies, this study demonstrated a lower incidence and delayed onset of HAdV infections and HAdV 3 was most prevalent in Korea.}, }
@article {pmid29566738, year = {2018}, author = {Singh, R and de Groot, PF and Geerlings, SE and Hodiamont, CJ and Belzer, C and Berge, IJMT and de Vos, WM and Bemelman, FJ and Nieuwdorp, M}, title = {Fecal microbiota transplantation against intestinal colonization by extended spectrum beta-lactamase producing Enterobacteriaceae: a proof of principle study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {190}, pmid = {29566738}, issn = {1756-0500}, support = {016.146.327//zonmw vidi/ ; 024.002.002//nwo gravitation grant/ ; }, mesh = {Adult ; Aged ; Enterobacteriaceae/enzymology/*physiology ; Enterobacteriaceae Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Male ; Middle Aged ; Time Factors ; Treatment Outcome ; Young Adult ; beta-Lactamases/*metabolism ; }, abstract = {OBJECTIVE: Infections with multidrug-resistant microorganisms are associated with increased hospitalization, medication costs and mortality. Based on our fecal microbiota transplantation (FMT) experience for Clostridium difficile infection, we treated 15 patients carrying ESBL-producing Enterobacteriaceae (ESBL-EB) with FMT. Seven patients underwent a second FMT after 4 weeks when ESBL-EB remained, amounting to a total number of 22 transplants. The objective was decolonization of ESBL-EB.<br><br>RESULTS: Three out of fifteen (20%) patients were ESBL-negative at 1, 2 and 4&#xa0;weeks after the first transplant, while six out of 15 (40%) were negative after the second transplant. Comparison of fecal microbiota at baseline and 4&#xa0;weeks after FMT revealed restoration of microbial diversity after FMT and a microbial shift towards donor composition. Finally, we suggest several possible factors of response to therapy, such as donor-recipient microbiota match and number of FMTs. Therefore, FMT can be an effective treatment in patients carrying ESBL-EB. Response may be determined by microbiota composition and number of FMT procedures. Trial registration ISRCTN ISRCTN48328635 Registered 11 October 2017, retrospectively registered.}, }
@article {pmid29566057, year = {2018}, author = {Thurner, M and Asim, F and Garczarczyk-Asim, D and Janke, K and Deutsch, M and Margreiter, E and Troppmair, J and Marksteiner, R}, title = {Development of an in vitro potency assay for human skeletal muscle derived cells.}, journal = {PloS one}, volume = {13}, number = {3}, pages = {e0194561}, pmid = {29566057}, issn = {1932-6203}, mesh = {Acetylcholinesterase/*metabolism ; Anal Canal/pathology ; Biopsy ; CD56 Antigen/metabolism ; Cell Count ; Cell Differentiation/*physiology ; Cell Separation/methods ; Cell Transplantation/legislation &amp; jurisprudence/methods ; Cells, Cultured ; Consumer Product Safety ; Double-Blind Method ; Enzyme Assays/methods ; Fecal Incontinence/etiology/pathology/*therapy ; Female ; Flow Cytometry ; GPI-Linked Proteins/metabolism ; Humans ; Male ; Muscle Fibers, Skeletal/pathology/*physiology/transplantation ; Muscular Diseases/complications/pathology/*therapy ; Placebos ; Treatment Outcome ; }, abstract = {BACKGROUND: Potency is a quantitative measure of the desired biological function of an advanced therapy medicinal product (ATMP) and is a prerequisite for market approval application (MAA). To assess the potency of human skeletal muscle-derived cells (SMDCs), which are currently investigated in clinical trials for the regeneration of skeletal muscle defects, we evaluated acetylcholinesterase (AChE), which is expressed in skeletal muscle and nervous tissue of all mammals.<br><br>METHODS: CD56+ SMDCs were separated from CD56- SMDCs by magnetic activated cell sorting (MACS) and both differentiated in skeletal muscle differentiation medium. AChE activity of in vitro differentiated SMDCs was correlated with CD56 expression, fusion index, cell number, cell doubling numbers, differentiation markers and compared to the clinical efficacy in patients treated with SMDCs against fecal incontinence.<br><br>RESULTS: CD56- SMDCs did not form multinucleated myotubes and remained low in AChE activity during differentiation. CD56+ SMDCs generated myotubes and increased in AChE activity during differentiation. AChE activity was found to accurately reflect the number of CD56+ SMDCs in culture, their fusion competence, and cell doubling number. In patients with fecal incontinence responding to SMDCs treatment, the improvement of clinical symptoms was positively linked with the AChE activity of the SMDCs injected.<br><br>DISCUSSION: AChE activity was found to truly reflect the in vitro differentiation status of SMDCs and to be superior to the mere use of surface markers as it reflects not only the number of myogenic SMDCs in culture but also their fusion competence and population doubling number, thus combining cell quality and quantification of the expected mode of action (MoA) of SMDCs. Moreover, the successful in vitro validation of the assay proves its suitability for routine use. Most convincingly, our results demonstrate a link between clinical efficacy and the AChE activity of the SMDCs preparations used for the treatment of fecal incontinence. Thus, we recommend using AChE activity of in vitro differentiated SMDCs as a potency measure in end stage (phase III) clinical trials using SMDCs for skeletal muscle regeneration and subsequent market approval application (MAA).}, }
@article {pmid29564854, year = {2018}, author = {Chuang, YT and Hwu, YJ}, title = {[Nursing Care of Older People With Clostridium Difficile Infection].}, journal = {Hu li za zhi The journal of nursing}, volume = {65}, number = {2}, pages = {27-31}, doi = {10.6224/JN.201804_65(2).05}, pmid = {29564854}, issn = {0047-262X}, mesh = {Aged ; Clostridium Infections/*nursing ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {The global incidence of Clostridium difficile infection (CDI) has increased in recent decades. The etiology of CDI includes aging as well as the misuse of antibiotics. This highly infectious disease requires that healthcare workers be vigilant and take isolation precautions, particularly in long-term facilities. CDI contributes to the development of severe diarrhea, which may cause imbalance of electrolytes, malabsorption of nutrients, physical disabilities, and psychosocial impacts in older patients. This article explores the pathophysiology, impacts, treatments (e.g., fecal microbiota transplantation [FMT]), and daily care regimens related to CDI with the goal of helping healthcare workers understand this disease and take action during the early stages of CDI.}, }
@article {pmid29564058, year = {2018}, author = {Patel, K and Patel, A and Hawes, D and Shah, J and Shah, K}, title = {Faecal microbiota transplantation: looking beyond clostridium difficile infection at inflammatory bowel disease.}, journal = {Gastroenterology and hepatology from bed to bench}, volume = {11}, number = {1}, pages = {1-8}, pmid = {29564058}, issn = {2008-2258}, abstract = {Gastrointestinal (GI) microbiota are known to play paramount role in inflammatory bowel disease (IBD). Innovative sequencing methods have radically expanded our ability to analyze the intestinal microbiome. However, alterations of the GI microbiome in IBD have not yet been fully evaluated. Irregular colonization of the gut has been implicated in chronic intestinal inflammation. Faecal microbiota transplantation (FMT) is a procedure which aims to restore microbial disturbances to the individual's gut microbiome. The success of FMT in Clostridium difficile infection (CDI) has inspired studies to explore transplantation in other conditions such as IBD. Ulcerative colitis (UC) and Crohn's disease (CD), the two principal manifestations of IBD, are emerging as a worldwide epidemic and are multifactorial in aetiology. There have been various case series in the past looking at the use of FMT in IBD, with a large number of them focusing on UC; however, two new randomized controlled trials shed up-to-date light on the complex interactions between the GI microbiome and patients. Regardless of these new studies, much more remains unknown about the efficacy and safety profile of FMT in IBD, ultimately casting a shadow over its use as a therapeutic intervention in conditions other than CDI. Further researches are necessary to fully evaluate the role of FMT as a management option in IBD. In this review, we discuss and summarize the functions of FMT in IBD, and the relationship between IBD and the GI microbial variations present.}, }
@article {pmid29562943, year = {2018}, author = {Pan, F and Zhang, L and Li, M and Hu, Y and Zeng, B and Yuan, H and Zhao, L and Zhang, C}, title = {Predominant gut Lactobacillus murinus strain mediates anti-inflammaging effects in calorie-restricted mice.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {54}, pmid = {29562943}, issn = {2049-2618}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Aging/immunology ; Animals ; Anti-Inflammatory Agents/*metabolism ; Antigens, Bacterial/blood ; Caco-2 Cells ; Caenorhabditis elegans/physiology ; Caloric Restriction/*methods ; Cell Line, Tumor ; Cell Membrane Permeability/physiology ; Endotoxins/blood ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/pathology ; Interleukin-8/biosynthesis ; Lactobacillus/*classification/isolation &amp; purification ; Longevity/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Tumor Necrosis Factor-alpha/blood ; }, abstract = {BACKGROUND: Calorie restriction (CR), which has a potent anti-inflammaging effect, has been demonstrated to induce dramatic changes in the gut microbiota. Whether the modulated gut microbiota contributes to the attenuation of inflammation during CR is unknown, as are the members of the microbial community that may be key mediators of this process.<br><br>RESULTS: Here, we report that a unique Lactobacillus-predominated microbial community was rapidly attained in mice within 2&#xa0;weeks of CR, which decreased the levels of circulating microbial antigens and systemic inflammatory markers such as tumour necrosis factor alpha (TNF-&#x3b1;). Lactobacillus murinus CR147, an isolate in the most abundant operational taxonomic unit (OTU) enriched by CR, downregulated interleukin-8 production in TNF-&#x3b1;-stimulated Caco-2 cells and significantly increased the lifespan and the brood size of the nematode Caenorhabditis elegans. In gnotobiotic mice colonized with the gut microbiota from old mice, this strain decreased their intestinal permeability and serum endotoxin load, consequently attenuating the inflammation induced by the old microbiota.<br><br>CONCLUSIONS: Our study demonstrated that a strain of Lactobacillus murinus was promoted in CR mice and causatively contributed to the attenuation of ageing-associated inflammation.}, }
@article {pmid29556726, year = {2018}, author = {Verstockt, B and Ferrante, M and Vermeire, S and Van Assche, G}, title = {New treatment options for inflammatory bowel diseases.}, journal = {Journal of gastroenterology}, volume = {53}, number = {5}, pages = {585-590}, pmid = {29556726}, issn = {1435-5922}, mesh = {Antibodies, Monoclonal, Humanized/therapeutic use ; Cell Adhesion Molecules/antagonists &amp; inhibitors ; Fecal Microbiota Transplantation ; Gastrointestinal Agents/*therapeutic use ; Humans ; Inflammatory Bowel Diseases/*therapy ; Interleukin-12/antagonists &amp; inhibitors ; Interleukin-23/antagonists &amp; inhibitors ; Janus Kinase Inhibitors/therapeutic use ; Mesenchymal Stem Cell Transplantation ; Ustekinumab/*therapeutic use ; }, abstract = {The advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD in the last 15 years, but primarily and more importantly secondary loss of response is often observed. Fortunately , new treatment options have been actively explored and some have already entered our clinical practice. In the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have entered clinical practice with the anti-p40 mAb ustekinumab in Crohn's disease (CD). Also, more selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream which have failed in clinical trials despite their clear efficacy in psoriasis (Verstockt et al. in Expert Opin Biol Ther 17(1):31-47, 2017; Verstockt et al. in Expert Opin Drug Saf 16(7):809-821, 2017). Following up on the efficacy of the anti-adhesion molecule vedolizumab, etrolizumab (anti-beta-7 integrin) and PF-00547659, an anti-MadCam mAb, are being developed (Lobaton et al. in Aliment Pharmacol Ther 39(6):579-594, 2014). Oral anti-trafficking agents, such as ozanimod, targeting the S1P receptor responsible for the efflux of T-cells from the lymph nodes, have also shown efficacy in patients with ulcerative colitis (UC) (Sandborn et al. in N Engl J Med 374(18):1754-1762, 2016). Oral agents inhibiting cell signaling have been explored successfully in IBD. Tofacitinib, a non-selective oral Janus kinase (JAK) inhibitor, is effective in patients with UC and several other more or less selective Jak1, 2 and 3 inhibitors are being developed for the treatment of CD and UC (Sandborn et al. in N Engl J Med 376(18):1723-1736, 2017; Vermeire et al. in Lancet 389(10066):266-275, 2017; De Vries et al. in J Crohns Colitis 11(7):885-93, 2017). Finally, despite initial disappointing results with systemic administration of mesenchymal stem cells, Alofisel, adipose tissue derived, allogeneic mesenchymal stem cells, locally injected in perianal fistula tracts, induce long-lasting beneficial effects and the drug has been approved in Europe (Panes et al. in Gastroenterology, 2017). In summary, the quest for new treatment options in IBD is very active and justified by the high medical need and unresolved problems patients are facing.}, }
@article {pmid29554669, year = {2018}, author = {Tansarli, GS and Mylonakis, E}, title = {Fecal transplant by oral capsule was noninferior to delivery by colonoscopy for C difficile recurrence.}, journal = {Annals of internal medicine}, volume = {168}, number = {6}, pages = {JC31}, doi = {10.7326/ACPJC-2018-168-6-031}, pmid = {29554669}, issn = {1539-3704}, mesh = {*Clostridioides difficile ; Colonoscopy ; Fecal Microbiota Transplantation ; Feces ; Humans ; Recurrence ; }, }
@article {pmid29538686, year = {2018}, author = {Gerding, DN and Kelly, CP and Rahav, G and Lee, C and Dubberke, ER and Kumar, PN and Yacyshyn, B and Kao, D and Eves, K and Ellison, MC and Hanson, ME and Guris, D and Dorr, MB}, title = {Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {67}, number = {5}, pages = {649-656}, pmid = {29538686}, issn = {1537-6591}, support = {P30 DK078392/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Antibodies, Monoclonal/*therapeutic use ; Antibodies, Neutralizing/*therapeutic use ; Broadly Neutralizing Antibodies ; Clostridioides difficile/drug effects ; Clostridium Infections/mortality/*prevention &amp; control ; Fecal Microbiota Transplantation ; Female ; Fidaxomicin/administration &amp; dosage ; Humans ; Male ; Metronidazole/administration &amp; dosage ; Middle Aged ; Patient Readmission ; Recurrence ; Risk Factors ; *Secondary Prevention ; Vancomycin/administration &amp; dosage ; Young Adult ; }, abstract = {BACKGROUND: Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C.difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI.<br><br>METHODS: The analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age &#x2265;65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented.<br><br>RESULTS: The majority of enrolled participants (75.6%) had &#x2265;1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; &#x2265;3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI.<br><br>CONCLUSIONS: The risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with &#x2265;3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit.<br><br>CLINICAL TRIALS REGISTRATION: NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).}, }
@article {pmid29538010, year = {2018}, author = {Choi, RY and Asquith, M and Rosenbaum, JT}, title = {Fecal transplants in spondyloarthritis and uveitis: ready for a clinical trial?.}, journal = {Current opinion in rheumatology}, volume = {30}, number = {4}, pages = {303-309}, doi = {10.1097/BOR.0000000000000506}, pmid = {29538010}, issn = {1531-6963}, support = {R01 EY018897/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/therapy ; Spondylarthritis/microbiology/*therapy ; Uveitis/microbiology/*therapy ; }, abstract = {PURPOSE OF REVIEW: The intestinal microbiome is thought to play a role in the pathogenesis of inflammatory bowel disease (IBD). There are many shared clinical manifestations between IBD and spondyloarthritis (SpA), of which the most common are peripheral arthritis and uveitis. Clinical overlap along with similar genetics between these diseases suggests a possible shared pathogenetic mechanism, which might center on the intestinal microbiota. In this review, we discuss the available evidence that SpA is a microbiome-driven disease and indicate how SpA-associated uveitis could be tied to gut dysbiosis. We conclude by discussing different treatment paradigms targeting the intestinal microbiome for SpA.<br><br>RECENT FINDINGS: Recent studies support the growing evidence of the intestinal microbiome as a crucial player in SpA disease pathogenesis. There is emerging evidence that the gut microbiome may play a causative role in uveitis.<br><br>SUMMARY: The field is beginning to discover a new level of understanding how the intestinal microbiome is involved in SpA. Treatment methods to alter intestinal microbiota to treat SpA-related diseases are still in its infancy.}, }
@article {pmid29537705, year = {2018}, author = {Perales-Puchalt, A and Perez-Sanz, J and Payne, KK and Svoronos, N and Allegrezza, MJ and Chaurio, RA and Anadon, C and Calmette, J and Biswas, S and Mine, JA and Costich, TL and Nickels, L and Wickramasinghe, J and Rutkowski, MR and Conejo-Garcia, JR}, title = {Frontline Science: Microbiota reconstitution restores intestinal integrity after cisplatin therapy.}, journal = {Journal of leukocyte biology}, volume = {103}, number = {5}, pages = {799-805}, pmid = {29537705}, issn = {1938-3673}, support = {P30 CA010815/CA/NCI NIH HHS/United States ; T32 CA009140/CA/NCI NIH HHS/United States ; P30 CA076292/CA/NCI NIH HHS/United States ; R01 CA124515/CA/NCI NIH HHS/United States ; T32 CA009171/CA/NCI NIH HHS/United States ; R01 CA157664/CA/NCI NIH HHS/United States ; R01 CA178687/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Cisplatin/*pharmacology ; Dysbiosis/mortality/pathology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Intestines/drug effects/*microbiology/pathology ; Ovarian Neoplasms/*drug therapy/microbiology/pathology ; Peritoneal Neoplasms/*drug therapy/microbiology/pathology ; Tumor Cells, Cultured ; }, abstract = {Due to their cytotoxic activities, many anticancer drugs cause extensive damage to the intestinal mucosa and have antibiotic activities. Here, we show that cisplatin induces significant changes in the repertoire of intestinal commensal bacteria that exacerbate mucosal damage. Restoration of the microbiota through fecal-pellet gavage drives healing of cisplatin-induced intestinal damage. Bacterial translocation to the blood stream is correspondingly abrogated, resulting in a significant reduction in systemic inflammation, as evidenced by decreased serum IL-6 and reduced mobilization of granulocytes. Mechanistically, reversal of dysbiosis in response to fecal gavage results in the production of protective mucins and mobilization of CD11b[+] myeloid cells to the intestinal mucosa, which promotes angiogenesis. Administration of Ruminococcus gnavus, a bacterial strain selectively depleted by cisplatin treatment, could only partially restore the integrity of the intestinal mucosa and reduce systemic inflammation, without measurable increases in the accumulation of mucin proteins. Together, our results indicate that reconstitution of the full repertoire of intestinal bacteria altered by cisplatin treatment accelerates healing of the intestinal epithelium and ameliorates systemic inflammation. Therefore, fecal microbiota transplant could paradoxically prevent life-threatening bacteremia in cancer patients treated with chemotherapy.}, }
@article {pmid29536125, year = {2018}, author = {von Braun, A and Lübbert, C}, title = {[Treatment of acute and recurrent Clostridium difficile infections : What is new?].}, journal = {Der Internist}, volume = {59}, number = {5}, pages = {505-513}, pmid = {29536125}, issn = {1432-1289}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/drug therapy ; Germany ; Humans ; Vancomycin/therapeutic use ; }, abstract = {The incidence of clostridium difficile infections (CDI) remains on a high level globally. In Germany, the number of severe or even lethal cases continues to increase. The main risk factor for the development of CDI is exposure to broad spectrum antibiotics, which disturb the physiological microbiome and therefore enable colonization with C. difficile. According to the updated US and European guidelines, orally administered vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin but has the advantage of a lower rate of recurrence. Furthermore, recent clinical studies were able to demonstrate that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. In recent years, several new antibiotics with narrow-spectrum acitivity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI; however, pivotal clinical trials have so far not been completed.}, }
@article {pmid29535530, year = {2018}, author = {Ramsay, I and Brown, NM and Enoch, DA}, title = {Recent Progress for the Effective Prevention and Treatment of Recurrent Clostridium difficile Infection.}, journal = {Infectious diseases}, volume = {11}, number = {}, pages = {1178633718758023}, pmid = {29535530}, issn = {1178-6337}, abstract = {Recurrence occurs in approximately 25% of all cases of Clostridium difficile infection (CDI) and poses a unique clinical challenge. Traditionally, treatment options of CDI have been limited to regimes of established antibiotics (eg, pulsed/tapered vancomycin) but faecal transplantation is emerging as a useful alternative. In recent years, promising new strategies have emerged for effective prevention of recurrent CDI (rCDI) including new antimicrobials (eg, fidaxomicin) and monoclonal antibodies (eg, bezlotoxumab). Despite promising progress in this area, obstacles remain for making the best use of these resources due to uncertainty over patient selection. This commentary describes the current epidemiology of rCDI, its clinical impact and risk factors, some of the measures used for treating and preventing rCDI, and some of the emerging treatment options. It then describes some of the obstacles that need to be overcome.}, }
@article {pmid29535482, year = {2017}, author = {Diamond, C and McNeilly, T}, title = {Faecal Microbiota Transplantation for Clostridium Difficile - a local perspective.}, journal = {The Ulster medical journal}, volume = {86}, number = {2}, pages = {108-110}, pmid = {29535482}, issn = {2046-4207}, mesh = {Aged ; Anti-Bacterial Agents/therapeutic use ; Catheter-Related Infections/microbiology/physiopathology/*therapy ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/diagnosis/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Northern Ireland ; Recurrence ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; Urinary Catheterization/*adverse effects/methods ; }, abstract = {Clostridium Difficile represents one of the major challenges of the antimicrobial era with associated significant morbidity. Treatment options are limited to a number of specific antibiotics with significant failure rates. Faecal Microbiota Transplantation has been recognised as a possible treatment option when standard therapy fails. We report a local case of Clostridium Difficile Infection ultimately requiring Faecal Microbiota Transplantation with good success. While no formal service providing the treatment is available within Northern Ireland it is a feasible treatment option for Clostridium Difficile Infection.}, }
@article {pmid29534703, year = {2018}, author = {Long, C and Yu, Y and Cui, B and Jagessar, SAR and Zhang, J and Ji, G and Huang, G and Zhang, F}, title = {A novel quick transendoscopic enteral tubing in mid-gut: technique and training with video.}, journal = {BMC gastroenterology}, volume = {18}, number = {1}, pages = {37}, pmid = {29534703}, issn = {1471-230X}, support = {81670495//National Natural Science Foundation of China (CN)/ ; 81600417//National Natural Science Foundation of China (CN)/ ; 2015BAI13B07//National Clinical Research Center for Digestive Diseases, Xi'an, China/ ; }, mesh = {Adult ; Endoscopy, Gastrointestinal/adverse effects/*methods ; Enteral Nutrition/methods ; Feasibility Studies ; Fecal Microbiota Transplantation/methods ; Female ; Humans ; Intubation, Gastrointestinal/adverse effects/*methods ; Male ; Patient Satisfaction ; Prospective Studies ; Surgical Instruments ; }, abstract = {BACKGROUND: This study aimed to evaluate the feasibility, safety, and value of a quick technique for transendoscopic enteral tubing (TET) through mid-gut.<br><br>METHODS: A prospective interventional study was performed in a single center. A TET tube was inserted into mid-gut through the nasal orifice and fixed on the pylorus wall by one tiny titanium endoscopic clip under anesthesia. The feasibility, safety, success rate, and satisfaction with TET placement were evaluated for enteral nutrition or fecal microbiota transplantation.<br><br>RESULTS: A total of 86 patients underwent mid-gut TET. The success rate of the TET procedure was 98.8% (85/86). Mean tubing time of the TET procedure was 4.2&#x2009;&#xb1;&#x2009;1.9&#xa0;min. 10 cases of procedure was enough for training of general endoscopist to shorten the procedure time (7.0&#xa0;min vs 4.0&#xa0;min, p&#x2009;<&#x2009;0.05). 97.7% (84/86) of patients were satisfied with the TET placement. Procedure-related and tube-related adverse events were observed in 8.1% (7/86) and 7.0% (6/86) of patients respectively. There were no moderate to severe adverse events during tube extubation.<br><br>CONCLUSIONS: TET through mid-gut is a novel, convenient, reliable and safe procedure for mid-gut administration with a high degree of patient satisfaction.<br><br>TRIAL REGISTRATION: This research was retrospectively registered with clinicaltrials.gov. Trial registration date: 29th November 2017.<br><br>TRIAL REGISTRATION NUMBER: NCT03335982 .}, }
@article {pmid29533199, year = {2018}, author = {Walker, MM and Potter, M and Talley, NJ}, title = {Eosinophilic gastroenteritis and other eosinophilic gut diseases distal to the oesophagus.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {3}, number = {4}, pages = {271-280}, doi = {10.1016/S2468-1253(18)30005-0}, pmid = {29533199}, issn = {2468-1253}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Diagnosis, Differential ; Diet Therapy ; *Enteritis/classification/diagnosis/etiology/therapy ; *Eosinophilia/classification/diagnosis/etiology/therapy ; Fecal Microbiota Transplantation ; *Gastritis/classification/diagnosis/etiology/therapy ; Gastrointestinal Agents/therapeutic use ; Humans ; }, abstract = {Under normal physiological conditions, eosinophils are present throughout the gastrointestinal tract distal to the squamous oesophagus. Increases in their numbers signify primary and secondary eosinophilic conditions. The rare primary eosinophilic diseases eosinophilic gastroenteritis and eosinophilic colitis affect fewer than ten in 100 000 people, and are characterised by numerous mucosal eosinophils, distributed in sheets and sometimes extending from the mucosa into the submucosa. Pathogenesis of these diseases is poorly understood, but food allergies and intestinal dysbiosis have been implicated. Presentation ranges from vague abdominal symptoms and systemic complaints to, rarely, an acute abdomen with intestinal obstruction. Diagnosis is made from mucosal biopsy samples taken at endoscopy or from surgically resected specimens that demonstrate substantially increased numbers of eosinophils. Eosinophilia secondary to other conditions, such as pathogenic infections, must be excluded. Subtle eosinophilia has also been identified in the duodenum in functional dyspepsia and in the colon in spirochaetosis. Treatment of eosinophilic gastroenteritis and eosinophilic colitis is based on evidence from case reports and small case series, and first-line therapy includes empirical food-elimination diets and single courses of steroids, whereas relapsing or refractory disease might respond to steroid-sparing immunosuppressive agents and biological agents. The progression of disease in eosinophilic gastroenteritis and eosinophilic colitis is variable: a considerable number of patients have just one episode without relapse, whereas others have relapsing-remitting or chronic disease. Primary and secondary eosinophilia in the gastrointestinal tract is increasingly recognised as a clinical conundrum waiting to be solved.}, }
@article {pmid29528385, year = {2018}, author = {Chen, T and Zhou, Q and Zhang, D and Jiang, F and Wu, J and Zhou, JY and Zheng, X and Chen, YG}, title = {Effect of Faecal Microbiota Transplantation for Treatment of Clostridium difficile Infection in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Cohort Studies.}, journal = {Journal of Crohn's &amp; colitis}, volume = {12}, number = {6}, pages = {710-717}, doi = {10.1093/ecco-jcc/jjy031}, pmid = {29528385}, issn = {1876-4479}, mesh = {*Clostridioides difficile ; Colitis, Ulcerative/*complications ; Crohn Disease/*complications ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Symptom Flare Up ; Treatment Outcome ; }, abstract = {BACKGROUND: Evidence concerning the effect of faecal microbiota transplantation [FMT] in Clostridium difficile infection [CDI] patients with inflammatory bowel disease [IBD] has not been firmly established. Therefore, we performed a systematic review and meta-analysis to evaluate FMT treatment outcomes in patients with IBD treated for CDI.<br><br>METHODS: An electronic search of four databases was conducted until November 1, 2017. Cohort studies of FMT efficacy and safety in CDI patients with IBD were included. Pooled effect sizes were calculated with 95% confidence intervals [CI] using a random-effects model.<br><br>RESULTS: Nine cohort studies comprising a total of 346 CDI patients with IBD were included. The initial cure rate was 81% [95% CI = 76%-85%] and the overall cure rate was up to 89% [95% CI = 83%-93%], both with no significant heterogeneity. The recurrence rate was 19% [95% CI = 13%-27%] with moderate heterogeneity [Cochran's Q, p = 0.19; I2 = 33%]. There was no significant difference in the CDI cure rate after FMT in patients with and without IBD (risk ratio [RR] = 0.92; 95% CI = 0.81-1.05; Cochran's Q, p = 0.06; I2 = 53%). Subgroup analysis revealed a similar CDI treatment effects after FMT in patients with Crohn's disease and in those with ulcerative colitis [p = 0.1804]. Four studies reported adverse events of IBD flares.<br><br>CONCLUSIONS: FMT is an effective therapy for CDI in patients with IBD. Well-designed randomised controlled trials and well-conducted microbiological studies are needed to validate its efficacy and safety.}, }
@article {pmid29521671, year = {2018}, author = {Roman, P and Abalo, R and Marco, EM and Cardona, D}, title = {Probiotics in digestive, emotional, and pain-related disorders.}, journal = {Behavioural pharmacology}, volume = {29}, number = {2 and 3-Spec Issue}, pages = {103-119}, doi = {10.1097/FBP.0000000000000385}, pmid = {29521671}, issn = {1473-5849}, mesh = {Animals ; Digestive System/drug effects ; Emotions/drug effects ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Pain/diet therapy/drug therapy ; Probiotics/*pharmacology/*therapeutic use ; }, abstract = {In recent years, interest in the relationship between gut microbiota and disease states has grown considerably. Indeed, several strategies have been employed to modify the microbiome through the administration of different diets, by the administration of antibiotics or probiotics, or even by transplantation of feces. In the present manuscript, we focus specifically on the potential application of probiotics, which seem to be a safe strategy, in the management of digestive, pain, and emotional disorders. We present evidence from animal models and human studies, notwithstanding that translation to clinic still deserves further investigation. The microbiome influences gut functions as well as neurological activity by a variety of mechanisms, which are also discussed. The design and performance of larger trials is urgently needed to verify whether these new strategies might be useful not only for the treatment of disorders affecting the gastrointestinal tract but also in the management of emotional and pain disorders not directly related to the gut.}, }
@article {pmid29521664, year = {2018}, author = {Goyal, H and Perisetti, A and Rehman, MR and Singla, U}, title = {New and emerging therapies in treatment of Clostridium difficile infection.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {30}, number = {6}, pages = {589-597}, doi = {10.1097/MEG.0000000000001103}, pmid = {29521664}, issn = {1473-5687}, mesh = {Anti-Bacterial Agents/adverse effects/*therapeutic use ; Clostridioides difficile/*drug effects/pathogenicity ; Clostridium Infections/diagnosis/microbiology/*therapy ; Cross Infection/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Metronidazole/adverse effects/*therapeutic use ; Recurrence ; Severity of Illness Index ; Treatment Outcome ; Vancomycin/adverse effects/*therapeutic use ; Vancomycin Resistance ; }, abstract = {Clostridium difficile infection (CDI) represents one of the most serious nosocomial infections that have grown dramatically over the past decade. Vancomycin and metronidazole are currently used as a standard therapy for CDI. Metronidazole is recommended as a first-line therapy for mild-to-moderate infections and vancomycin is mainly used for severe and/or refractory cases. However, studies have demonstrated that there are quite high CDI relapse rates with both of these medications, which represents a challenge for clinicians. Over the last decade, a number of newer and novel therapeutic options have emerged as promising alternatives to these standard CDI therapies. The following review provides the updated summaries of these newer therapeutic agents and their status in the treatment of CDI.}, }
@article {pmid29519860, year = {2018}, author = {Li, X and Guo, X and Jin, W and Lu, J}, title = {Effects of electroacupuncture combined with stem cell transplantation on anal sphincter injury-induced faecal incontinence in a rat model.}, journal = {Acupuncture in medicine : journal of the British Medical Acupuncture Society}, volume = {36}, number = {4}, pages = {254-260}, doi = {10.1136/acupmed-2016-011262}, pmid = {29519860}, issn = {1759-9873}, mesh = {Anal Canal/*injuries/metabolism ; Animals ; Chemokine CCL7/genetics/metabolism ; Chemokine CXCL12/genetics/metabolism ; *Electroacupuncture ; Fecal Incontinence/genetics/metabolism/*therapy ; Humans ; Male ; *Mesenchymal Stem Cell Transplantation ; Rats ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) and acupuncture are known to mitigate tissue damage. This study aimed to investigate the therapeutic effects of combined electroacupuncture (EA) stimulation and BMSC injection in a rat model of anal sphincter injury-induced faecal incontinence (FI).<br><br>METHODS: 60 Sprague-Dawley rats were randomly divided into five groups: sham-operated control, FI, FI+EA, FI+BMSC, and FI+BMSC+EA. The anorectal tissues were collected on days 1, 3, 7 and 14. Repair of the injured anal sphincter was compared using haematoxylin and eosin (HE) and immunocytochemiscal analyses with sarcomeric &#x3b1; actinin. The expression of stromal cell derived factor-1 (SDF-1) and monocyte chemoattractant protein-3 (MCP-3) was detected by quantitative reverse transcription PCR to evaluate the effects of EA on the homing of BMSCs.<br><br>RESULTS: The therapeutic effect of combined EA+BMSCs on damaged tissue was the strongest among all the groups as indicated by HE and immunohistochemical staining. The expression of SDF-1 and MCP-3 was significantly increased by combined EA and BMSC treatment when compared with the other groups (P=0.01 to P<0.05), suggesting promotive effects of EA on the homing of BMSCs.<br><br>CONCLUSION: The combination of EA and BMSC transplantation effectively repaired the impaired anal sphincters. The underlying mechanism might be associated with apparent promotive effects of EA on the homing of BMSCs. Our study provides a theoretical basis for the development of a non-surgical treatment method for FI secondary to muscle impairment.}, }
@article {pmid29514066, year = {2018}, author = {Bauer, PV and Duca, FA and Waise, TMZ and Dranse, HJ and Rasmussen, BA and Puri, A and Rasti, M and O'Brien, CA and Lam, TKT}, title = {Lactobacillus gasseri in the Upper Small Intestine Impacts an ACSL3-Dependent Fatty Acid-Sensing Pathway Regulating Whole-Body Glucose Homeostasis.}, journal = {Cell metabolism}, volume = {27}, number = {3}, pages = {572-587.e6}, doi = {10.1016/j.cmet.2018.01.013}, pmid = {29514066}, issn = {1932-7420}, support = {FDN-143204//CIHR/Canada ; }, mesh = {Animals ; Coenzyme A Ligases/*metabolism ; Diet, High-Fat/methods ; Emulsions/metabolism ; Fatty Acids/*metabolism ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Glucose/*metabolism ; Homeostasis ; Intestine, Small/*metabolism/*microbiology ; Lactobacillus gasseri/*metabolism ; Linoleic Acid/metabolism ; Mice, Inbred C57BL ; Oleic Acid/metabolism ; Phospholipids/metabolism ; Rats, Sprague-Dawley ; Soybean Oil/metabolism ; }, abstract = {Long-chain acyl-CoA synthetase (ACSL)-dependent upper small intestinal lipid metabolism activates pre-absorptive pathways to regulate metabolic homeostasis, but whether changes in the upper small intestinal microbiota alter specific fatty acid-dependent pathways to impact glucose homeostasis remains unknown. We here first find that upper small intestinal infusion of Intralipid, oleic acid, or linoleic acid pre-absorptively increases glucose tolerance and lowers glucose production in rodents. High-fat feeding impairs pre-absorptive fatty acid sensing and reduces upper small intestinal Lactobacillus gasseri levels and ACSL3 expression. Transplantation of healthy upper small intestinal microbiota to high-fat-fed rodents restores L. gasseri levels and fatty acid sensing via increased ACSL3 expression, while L. gasseri probiotic administration to non-transplanted high-fat-fed rodents is sufficient to restore upper small intestinal ACSL3 expression and fatty acid sensing. In summary, we unveil a glucoregulatory role of upper small intestinal L. gasseri that impacts an ACSL3-dependent glucoregulatory fatty acid-sensing pathway.}, }
@article {pmid29507020, year = {2018}, author = {Digby-Bell, J and Williams, A and Irving, P and Goldenberg, S}, title = {Successful faecal microbiota transplant for recurrent Clostridium difficile infection delivered by colonoscopy through a diverted ileostomy in a patient with severe perianal Crohn's disease.}, journal = {BMJ case reports}, volume = {2018}, number = {}, pages = {}, pmid = {29507020}, issn = {1757-790X}, mesh = {Adult ; Clostridium Infections/complications/*therapy ; Colonoscopes ; Colonoscopy/*methods ; Crohn Disease/complications ; Fecal Microbiota Transplantation/instrumentation/*methods ; Female ; Humans ; *Ileostomy ; Treatment Outcome ; }, abstract = {We present the first reported case of successful treatment of recurrent Clostridium difficile infection with faecal microbiota transplantation delivered antegrade with a colonoscope through a diverting ileostomy.}, }
@article {pmid29500907, year = {2018}, author = {Bajaj, JS and Kakiyama, G and Cox, IJ and Nittono, H and Takei, H and White, M and Fagan, A and Gavis, EA and Heuman, DM and Gilles, HC and Hylemon, P and Taylor-Robinson, SD and Legido-Quigley, C and Kim, M and Xu, J and Williams, R and Sikaroodi, M and Pandak, WM and Gillevet, PM}, title = {Alterations in gut microbial function following liver transplant.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {24}, number = {6}, pages = {752-761}, pmid = {29500907}, issn = {1527-6473}, support = {I01 BX001328/BX/BLRD VA/United States ; I01 CX001076/CX/CSRD VA/United States ; R01 DK087913/DK/NIDDK NIH HHS/United States ; I01 BX000197/BX/BLRD VA/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; }, mesh = {Bile Acids and Salts/blood ; Cognition/physiology ; Dysbiosis/blood/*microbiology/physiopathology ; End Stage Liver Disease/blood/microbiology/*surgery ; Endotoxemia/diagnosis/microbiology/physiopathology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Lipid Metabolism/physiology ; Liver/metabolism/surgery ; Liver Cirrhosis/blood/microbiology/*surgery ; Liver Function Tests ; *Liver Transplantation ; Male ; Metabolome/physiology ; Middle Aged ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {Liver transplantation (LT) improves daily function and ameliorates gut microbial composition. However, the effect of LT on microbial functionality, which can be related to overall patient benefit, is unclear and could affect the post-LT course. The aims were to determine the effect of LT on gut microbial functionality focusing on endotoxemia, bile acid (BA), ammonia metabolism, and lipidomics. We enrolled outpatient patients with cirrhosis on the LT list and followed them until 6 months after LT. Microbiota composition (Shannon diversity and individual taxa) and function analysis (serum endotoxin, urinary metabolomics and serum lipidomics, and stool BA profile) and cognitive tests were performed at both visits. We enrolled 40 patients (age, 56 ± 7 years; mean Model for End-Stage Liver Disease score, 22.6). They received LT 6 ± 3 months after enrollment and were re-evaluated 7 ± 3 months after LT with a stable course. A significant improvement in cognition with increase in microbial diversity, increase in autochthonous and decrease in potentially pathogenic taxa, and reduced endotoxemia were seen after LT compared with baseline. Stool BAs increased significantly after LT, and there was evidence of greater bacterial action (higher secondary, oxo and iso-BAs) after LT although the levels of conjugated BAs remained similar. There was a reduced serum ammonia and corresponding rise in urinary phenylacetylglutamine after LT. There was an increase in urinary trimethylamine-N-oxide, which was correlated with specific changes in serum lipids related to cell membrane products. The ultimate post-LT lipidomic profile appeared beneficial compared with the profile before LT. In conclusion, LT improves gut microbiota diversity and dysbiosis, which is accompanied by favorable changes in gut microbial functionality corresponding to BAs, ammonia, endotoxemia, lipidomic, and metabolomic profiles. Liver Transplantation 24 752-761 2018 AASLD.}, }
@article {pmid29498019, year = {2018}, author = {Rodiño-Janeiro, BK and Vicario, M and Alonso-Cotoner, C and Pascua-García, R and Santos, J}, title = {A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies.}, journal = {Advances in therapy}, volume = {35}, number = {3}, pages = {289-310}, pmid = {29498019}, issn = {1865-8652}, mesh = {Diet Therapy ; Dietary Supplements ; *Gastrointestinal Microbiome/drug effects/physiology ; Humans ; *Irritable Bowel Syndrome/immunology/microbiology/psychology/therapy ; Patient Care Management/*methods ; *Quality of Life ; }, abstract = {Irritable bowel syndrome (IBS), one of the most frequent digestive disorders, is characterized by chronic and recurrent abdominal pain and altered bowel habit. The origin seems to be multifactorial and is still not well defined for the different subtypes. Genetic, epigenetic and sex-related modifications of the functioning of the nervous and immune-endocrine supersystems and regulation of brain-gut physiology and bile acid production and absorption are certainly involved. Acquired predisposition may act in conjunction with infectious, toxic, dietary and life event-related factors to enhance epithelial permeability and elicit mucosal microinflammation, immune activation and dysbiosis. Notably, strong evidence supports the role of bacterial, viral and parasitic infections in triggering IBS, and targeting microbiota seems promising in view of the positive response to microbiota-related therapies in some patients. However, the lack of highly predictive diagnostic biomarkers and the complexity and heterogeneity of IBS patients make management difficult and unsatisfactory in many cases, reducing patient health-related quality of life and increasing the sanitary burden. This article reviews specific alterations and interventions targeting the gut microbiota in IBS, including prebiotics, probiotics, synbiotics, non-absorbable antibiotics, diets, fecal transplantation and other potential future approaches useful for the diagnosis, prevention and treatment of IBS.}, }
@article {pmid29497269, year = {2017}, author = {Nascimento, MM}, title = {Oral microbiota transplant: a potential new therapy for oral diseases.}, journal = {Journal of the California Dental Association}, volume = {45}, number = {10}, pages = {565-568}, pmid = {29497269}, issn = {1043-2256}, support = {K23 DE023579/DE/NIDCR NIH HHS/United States ; }, mesh = {Dental Caries ; Dental Plaque ; Humans ; *Microbiota ; Mouth/*microbiology ; Mouth Diseases/*therapy ; Periodontitis ; }, abstract = {Dental caries and periodontitis are amongst the most common diseases affecting humans worldwide. There is an evolving trend for dental and medical research to share knowledge on the etiology and promising therapies for human diseases. Inspired by the success of fecal microbiota transplant to manage gastro-intestinal disordes, oral microbiome transplant has been proposed but not yet tested in humans. This article critically reviews the potential of oral microbiome transplant for managing oral diseases.}, }
@article {pmid29493330, year = {2018}, author = {El-Salhy, M and Mazzawi, T}, title = {Fecal microbiota transplantation for managing irritable bowel syndrome.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {12}, number = {5}, pages = {439-445}, doi = {10.1080/17474124.2018.1447380}, pmid = {29493330}, issn = {1747-4132}, mesh = {Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Irritable Bowel Syndrome/diagnosis/microbiology/*therapy ; Treatment Outcome ; }, abstract = {Irritable bowel syndrome (IBS) is a widespread gastrointestinal disorder affecting 11.2% of the world adult population. The intestinal microbiome is thought to play a pivotal role in the pathophysiology of IBS. The composition of the fecal microbiome in IBS patients differs from that in healthy individuals, but the exact bacteria species involved in the development of IBS remain to be determined. There is also an imbalance between useful and harmful bacteria (dysbiosis) in the intestinal microbiome in patients with IBS. Consuming prebiotics, probiotics, or synbiotics has a limited effect on IBS symptoms. In contrast, fecal microbiome transplantation (FMT) in IBS patients reverses the dysbiosis to normobiosis and reduces the IBS symptoms in about 70% of patients, and is not associated with any serious adverse events. Area covered: The available data on the microbiome and FMT in IBS regarding the efficacy of FMT in managing IBS were found using a PubMed search of these topics. Expert commentary: FMT is a promising tool for managing irritable syndrome. It appears to be effective, easy, and inexpensive procedure. However, more controlled studies involving larger cohorts of IBS are needed before FMT can be used as a routine procedure in the clinic.}, }
@article {pmid29492875, year = {2018}, author = {Cho, JA and Chinnapen, DJF}, title = {Targeting friend and foe: Emerging therapeutics in the age of gut microbiome and disease.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {56}, number = {3}, pages = {183-188}, pmid = {29492875}, issn = {1976-3794}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Dysbiosis/microbiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/etiology/*therapy ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*drug effects/microbiology/physiopathology ; Humans ; Hypersensitivity/etiology/therapy ; Inflammatory Bowel Diseases/etiology/therapy ; Neoplasms/therapy ; Obesity/etiology/therapy ; Probiotics/*therapeutic use ; Symbiosis ; }, abstract = {Mucosal surfaces that line our gastrointestinal tract are continuously exposed to trillions of bacteria that form a symbiotic relationship and impact host health and disease. It is only beginning to be understood that the cross-talk between the host and microbiome involve dynamic changes in commensal bacterial population, secretion, and absorption of metabolites between the host and microbiome. As emerging evidence implicates dysbiosis of gut microbiota in the pathology and progression of various diseases such as inflammatory bowel disease, obesity, and allergy, conventional treatments that either overlook the microbiome in the mechanism of action, or eliminate vast populations of microbes via wide-spectrum antibiotics need to be reconsidered. It is also becoming clear the microbiome can influence the body's response to therapeutic treatments for cancers. As such, targeting the microbiome as treatment has garnered much recent attention and excitement from numerous research labs and biotechnology companies. Treatments range from fecal microbial transplantation to precision-guided molecular approaches. Here, we survey recent progress in the development of innovative therapeutics that target the microbiome to treat disease, and highlight key findings in the interplay between host microbes and therapy.}, }
@article {pmid29488356, year = {2018}, author = {Arulkumaran, N and Sixma, ML and Pollen, S and Ceravola, E and Jentho, E and Prendecki, M and Bass, PS and Tam, FWK and Unwin, RJ and Singer, M}, title = {P2X7 receptor antagonism ameliorates renal dysfunction in a rat model of sepsis.}, journal = {Physiological reports}, volume = {6}, number = {5}, pages = {}, pmid = {29488356}, issn = {2051-817X}, support = {093969/10/Z//Wellcome Trust/United Kingdom ; }, mesh = {Acute Kidney Injury/*drug therapy/etiology ; Animals ; Anti-Inflammatory Agents/*therapeutic use ; Cells, Cultured ; Creatinine/blood ; Interleukin-1beta/blood ; Male ; Peritonitis/complications/*drug therapy ; Purinergic P2X Receptor Antagonists/*therapeutic use ; Pyridines/*therapeutic use ; Rats ; Rats, Wistar ; Shock, Septic/*drug therapy/etiology ; Tetrazoles/*therapeutic use ; }, abstract = {Sepsis is a major clinical problem associated with significant organ dysfunction and high mortality. The ATP-sensitive P2X7 receptor activates the NLRP3 inflammasome and is a key component of the innate immune system. We used a fluid-resuscitated rat model of fecal peritonitis and acute kidney injury (AKI) to investigate the contribution of this purinergic receptor to renal dysfunction in sepsis. Six and 24 h time-points were chosen to represent early and established sepsis, respectively. A selective P2X7 receptor antagonist (A-438079) dissolved in dimethyl sulfoxide (DMSO) was infused 2 h following induction of sepsis. Compared with sham-operated animals, septic animals had significant increases in heart rate (-1(-4 to 8)% vs. 21(12-26)%; P = 0.003), fever (37.4(37.2-37.6)°C vs. 38.6(38.2-39.0)°C; P = 0.0009), and falls in serum albumin (29(27-30)g/L vs. 26(24-28); P = 0.0242). Serum IL-1β (0(0-10)(pg/mL) vs. 1671(1445-33778)(pg/mL); P < 0.001) and renal IL-1β (86(50-102)pg/mg protein vs. 200 (147-248)pg/mg protein; P = 0.0031) were significantly elevated in septic compared with sham-operated animals at 6 h. Serum creatinine was elevated in septic animals compared with sham-operated animals at 24 h (23(22-25) μmol/L vs. 28 (25-30)μmol/L; P = 0.0321). Renal IL-1β levels were significantly lower in A-438079-treated animals compared with untreated animals at 6 h (70(55-128)pg/mg protein vs. 200(147-248)pg/mg protein; P = 0.021). At 24 h, compared with untreated animals, A-438079-treated animals had more rapid resolution of tachycardia (22(13-36)% vs. -1(-6 to 7)%; P = 0.019) and fever (39.0(38.6-39.1)°C vs. 38.2(37.6-38.7)°C; P < 0.024), higher serum albumin (23(21-25)g/L vs. (27(25-28)g/L); P = 0.006), lower arterial lactate (3.2(2.5-4.3)mmol/L vs. 1.4(0.9-1.8)mmol/L; P = 0.037), and lower serum creatinine concentrations (28(25-30)μmol/L vs. 22(17-27)μmol/L; P = 0.019). P2X7 A treatment ameliorates the systemic inflammatory response and renal dysfunction in this clinically relevant model of sepsis-related AKI.}, }
@article {pmid29487424, year = {2018}, author = {Dickson, I}, title = {Therapy: FMT: the rules of engraftment.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {15}, number = {4}, pages = {190-191}, pmid = {29487424}, issn = {1759-5053}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid29486930, year = {2018}, author = {The Lancet, }, title = {A new approach to treating infection.}, journal = {Lancet (London, England)}, volume = {391}, number = {10122}, pages = {714}, doi = {10.1016/S0140-6736(18)30320-9}, pmid = {29486930}, issn = {1474-547X}, mesh = {*Clostridioides difficile ; Clostridium Infections/diagnosis/*therapy ; Cross Infection/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Infection Control ; }, }
@article {pmid29484160, year = {2018}, author = {Ding, NS and Mullish, BH and McLaughlin, J and Hart, A and Marchesi, JR}, title = {Meeting update: faecal microbiota transplantation--bench, bedside, courtroom?.}, journal = {Frontline gastroenterology}, volume = {9}, number = {1}, pages = {45-48}, pmid = {29484160}, issn = {2041-4137}, }
@article {pmid29479439, year = {2018}, author = {Hopkins, RJ and Wilson, RB}, title = {Treatment of recurrent Clostridium difficile colitis: a narrative review.}, journal = {Gastroenterology report}, volume = {6}, number = {1}, pages = {21-28}, pmid = {29479439}, issn = {2052-0034}, abstract = {Clostridium difficile is a gram-positive, spore-forming, obligate anaerobic bacillus that was originally isolated from the stool of a healthy neonate in 1935. In high-income countries, C. difficile is the most common cause of infectious diarrhoea in hospitalized patients. The incidence of C. difficile infection in the USA has increased markedly since 2000, with hospitalizations for C. difficile infections in non-pregnant adults doubling between 2000 and 2010. Between 20% and 35% of patients with C. difficile infection will fail initial antibiotic treatment and, of these, 40-60% will have a second recurrence. Recurrence of C. difficile infection after initial treatment causes substantial morbidity and is a major burden on health care systems. In this article, current treatments for recurrent C. difficile infection are reviewed and future directions explored. These include the use of antibiotics, probiotics, donor faecal transplants, anion resins, secondary bile acids or anti-toxin antibodies.}, }
@article {pmid29477634, year = {2018}, author = {Dinh, A and Fessi, H and Duran, C and Batista, R and Michelon, H and Bouchand, F and Lepeule, R and Vittecoq, D and Escaut, L and Sobhani, I and Lawrence, C and Chast, F and Ronco, P and Davido, B}, title = {Clearance of carbapenem-resistant Enterobacteriaceae vs vancomycin-resistant enterococci carriage after faecal microbiota transplant: a prospective comparative study.}, journal = {The Journal of hospital infection}, volume = {99}, number = {4}, pages = {481-486}, doi = {10.1016/j.jhin.2018.02.018}, pmid = {29477634}, issn = {1532-2939}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteriological Techniques ; Carbapenem-Resistant Enterobacteriaceae/*isolation &amp; purification ; Carrier State/microbiology/*therapy ; Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology ; Enterobacteriaceae Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gram-Positive Bacterial Infections/microbiology/*therapy ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Prospective Studies ; Treatment Outcome ; Vancomycin-Resistant Enterococci/*isolation &amp; purification ; Young Adult ; }, abstract = {BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant enterococci (VRE) carriage are increasing worldwide. Faecal microbiota transplantation (FMT) appears to be an attractive option for decolonization. This study aimed to evaluate CRE vs VRE clearance by FMT among carriers.<br><br>METHODS: A multi-centre trial was undertaken on patients with CRE or VRE digestive tract colonization who received FMT between January 2015 and April 2017. Adult patients with CRE or VRE colonization, confirmed by three consecutive rectal swabs at weekly intervals, including one in the week prior to FMT, were included in the study. Patients with immunosuppression or concomitant antibiotic prescription at the time of FMT were excluded. Successful decolonization was determined by at least two consecutive negative rectal swabs [polymerase chain reaction (PCR) and culture] on Days 7, 14, 21 and 28, and monthly for three months following FMT.<br><br>RESULTS: Seventeen patients were included, with a median age of 73 years [interquartile range (IQR) 64.3-79.0]. Median duration of carriage of CRE or VRE before FMT was 62.5 days (IQR 57.0-77.5). One week after FMT, three of eight patients were free of CRE colonization and three of nine patients were free of VRE colonization. After three months, four of eight patients were free of CRE colonization and seven of eight patients were free of VRE colonization. Qualitative PCR results were concordant with culture. Six patients received antibiotics during follow-up, three in each group. No adverse events were reported.<br><br>CONCLUSION: CRE and VRE clearance rates were not significantly different in this study, possibly due to the small sample size, but a trend was observed. These data should be confirmed by larger cohorts and randomized trials.}, }
@article {pmid29474356, year = {2018}, author = {Martinez-Perez, A and Roure Díez, S and Belhassen-Garcia, M and Torrús-Tendero, D and Perez-Arellano, JL and Cabezas, T and Soler, C and Díaz-Menéndez, M and Navarro, M and Treviño, B and Salvador, F and , }, title = {Management of severe strongyloidiasis attended at reference centers in Spain.}, journal = {PLoS neglected tropical diseases}, volume = {12}, number = {2}, pages = {e0006272}, pmid = {29474356}, issn = {1935-2735}, mesh = {Adult ; Aged ; Albendazole/administration &amp; dosage/therapeutic use ; Animals ; Antiparasitic Agents/administration &amp; dosage/therapeutic use ; Communicable Diseases, Imported/drug therapy/epidemiology/parasitology/*therapy ; Comorbidity ; *Disease Management ; Emigrants and Immigrants ; Feces/parasitology ; Female ; Humans ; Immunocompromised Host ; Ivermectin/administration &amp; dosage/therapeutic use ; Larva/physiology ; Male ; Middle Aged ; Referral and Consultation ; Retrospective Studies ; Spain/epidemiology ; Strongyloides stercoralis/*drug effects/isolation &amp; purification ; Strongyloidiasis/diagnosis/drug therapy/*epidemiology/*therapy ; Young Adult ; }, abstract = {INTRODUCTION: Strongyloides stercoralis is a globally distributed nematode that causes diverse clinical symptoms in humans. Spain, once considered an endemic country, has experienced a recent increase in imported cases. The introduction of serology helps diagnosis and is currently replacing microbiological techniques in some settings, but its sensitivity is variable and can be low in immunocompromised patients. Diagnosis can only be confirmed by identification of larvae. Often, this "gold standard" can only be achieved in severe cases, such as disseminated S.stercoralis infection, or S.stercoralis hyperinfection syndrome, where parasite load is high. In addition, these clinical presentations are not well-defined. Our aim is to describe severe cases of S.stercoralis, their epidemiological profile, and their clinical details.<br><br>METHODS: An observational retrospective study of disseminated S.stercoralis infection, or hyperinfection syndrome. Inclusion criteria: aged over 18, with a diagnosis of disseminated S.stercoralis infection, or hyperinfection syndrome, confirmed by visualization of larvae. Patients were identified through revision of clinical records for the period 2000-2015, in collaboration with eight reference centers throughout Spain.<br><br>RESULTS: From the period 2000-2015, eighteen cases were identified, 66.7% of which were male, with a median age of 40 (range 21-70). Most of them were foreigners (94.4%), mainly from Latin America (82.3%) or Western Africa (17.6%). Only one autochthonous case was identified, from 2006. Immunosuppressive conditions were present in fourteen (77%) patients, mainly due steroids use and to retroviral coinfections (four HIV, two HTLV). Transplant preceded the clinical presentation in four of them. Other comorbidities were coinfection with HBV, Trypanosoma cruzi, Mycobacterium leprae or Aspergillus spp. All presented with digestive disorders, with 55.6% also presenting malaise. 44.4% of cases had fever, 27.8% skin complaints, and 16.7% respiratory or neurological disorders. One patient presented anemia, and one other nephrotic syndrome. Diagnosis was confirmed by identification of larvae in fresh stool samples (n = 16; 88.9%), concentration techniques (n = 6; 33.3%), larval culture (n = 5; 29.4%), or digestive biopsies (n = 8; 44%). S.stercoralis forms were identified during necropsy in one case. In addition, ten (55%) had a positive serology. All the cases were treated with ivermectin, six (33%) also received albendazole and one case received thiabendazole followed by ivermectin. All needed inpatient management, involving a mean hospitalization stay of 25 days (range 1-164). Two cases received intensive care and eventually died.<br><br>CONCLUSIONS: Only eighteen cases of disseminated S.stercoralis infection/hyperinfection syndrome were identified from the 15-year period, most of which were considered to have been imported cases. Among those, immunosuppression was frequent, and mortality due to S.stercoralis was lower than previously described.}, }
@article {pmid29471034, year = {2018}, author = {Andermann, TM and Peled, JU and Ho, C and Reddy, P and Riches, M and Storb, R and Teshima, T and van den Brink, MRM and Alousi, A and Balderman, S and Chiusolo, P and Clark, WB and Holler, E and Howard, A and Kean, LS and Koh, AY and McCarthy, PL and McCarty, JM and Mohty, M and Nakamura, R and Rezvani, K and Segal, BH and Shaw, BE and Shpall, EJ and Sung, AD and Weber, D and Whangbo, J and Wingard, JR and Wood, WA and Perales, MA and Jenq, RR and Bhatt, AS and , }, title = {The Microbiome and Hematopoietic Cell Transplantation: Past, Present, and Future.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {24}, number = {7}, pages = {1322-1340}, pmid = {29471034}, issn = {1523-6536}, support = {U10 HL069294/HL/NHLBI NIH HHS/United States ; UG1 HL069301/HL/NHLBI NIH HHS/United States ; K08 CA184420/CA/NCI NIH HHS/United States ; UG1 HL069315/HL/NHLBI NIH HHS/United States ; U10 HL069330/HL/NHLBI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; UG1 HL069278/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; U24 CA076518/CA/NCI NIH HHS/United States ; U24 HL138660/HL/NHLBI NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; UG1 HL069330/HL/NHLBI NIH HHS/United States ; }, mesh = {*Hematopoietic Stem Cell Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid29471030, year = {2018}, author = {Sun, MF and Zhu, YL and Zhou, ZL and Jia, XB and Xu, YD and Yang, Q and Cui, C and Shen, YQ}, title = {Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway.}, journal = {Brain, behavior, and immunity}, volume = {70}, number = {}, pages = {48-60}, doi = {10.1016/j.bbi.2018.02.005}, pmid = {29471030}, issn = {1090-2139}, mesh = {Animals ; Brain ; Disease Models, Animal ; Dysbiosis/metabolism/physiopathology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Microglia ; Neuroglia/drug effects ; Neuroprotective Agents ; Parkinson Disease/physiopathology/*therapy ; RNA, Ribosomal, 16S/genetics ; Toll-Like Receptor 4/drug effects/metabolism ; Tumor Necrosis Factor-alpha/drug effects/metabolism ; }, abstract = {Parkinson's disease (PD) patients display alterations in gut microbiota composition. However, mechanism between gut microbial dysbiosis and pathogenesis of PD remains unexplored, and no recognized therapies are available to halt or slow progression of PD. Here we identified that gut microbiota from PD mice induced motor impairment and striatal neurotransmitter decrease on normal mice. Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales decreased, while phylum Proteobacteria, order Turicibacterales and Enterobacteriales increased in fecal samples of PD mice, along with increased fecal short-chain fatty acids (SCFAs). Remarkably, fecal microbiota transplantation (FMT) reduced gut microbial dysbiosis, decreased fecal SCFAs, alleviated physical impairment, and increased striatal DA and 5-HT content of PD mice. Further, FMT reduced the activation of microglia and astrocytes in the substantia nigra, and reduced expression of TLR4/TNF-α signaling pathway components in gut and brain. Our study demonstrates that gut microbial dysbiosis is involved in PD pathogenesis, and FMT can protect PD mice by suppressing neuroinflammation and reducing TLR4/TNF-α signaling.}, }
@article {pmid29470297, year = {2018}, author = {Barnes, D and Ng, K and Smits, S and Sonnenburg, J and Kassam, Z and Park, KT}, title = {Competitively Selected Donor Fecal Microbiota Transplantation: Butyrate Concentration and Diversity as Measures of Donor Quality.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {67}, number = {2}, pages = {185-187}, doi = {10.1097/MPG.0000000000001940}, pmid = {29470297}, issn = {1536-4801}, mesh = {Adolescent ; Adult ; Butyrates/*analysis ; Child ; Clostridium Infections/*therapy ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/*chemistry/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Prospective Studies ; *Tissue Donors ; Treatment Outcome ; Young Adult ; }, abstract = {In this prospective cohort study, we examine the feasibility of a protocol to optimize microbiota for fecal microbiota transplantation (FMT). Donor stool metrics generally accepted as markers of gut health were used to select a stool donor based on superior microbial diversity, balanced constitution of Bacteroidetes versus Firmicutes and high concentration of fecal butyrate. Selected donor microbiota was then administered via FMT. A total of 10 patients with median age of 12 years with recurrent Clostridium difficile infection received the intervention. The rate of recurrence-free resolution with 1-2 FMTs was 100% at Week 10. With a single FMT, 80% of patients cleared Clostridium difficile infection without recurrence, whereas 20% of patients required a single re-treatment. No serious adverse events occurred. Microbiota sequencing revealed that recipients' gut microbiota phylogenic diversity increased by 72-hours post-transplantation, with sustainment over 10-week follow-up. This study highlights the feasibility of purposefully selecting the most ideal microbiota for transplantation.}, }
@article {pmid29469650, year = {2018}, author = {Sherman, SB and Sarsour, N and Salehi, M and Schroering, A and Mell, B and Joe, B and Hill, JW}, title = {Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis.}, journal = {Gut microbes}, volume = {9}, number = {5}, pages = {400-421}, pmid = {29469650}, issn = {1949-0984}, support = {P30 DK020572/DK/NIDDK NIH HHS/United States ; U54 HD028934/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Animals ; Female ; Humans ; Pregnancy ; Rats ; Adipokines/metabolism ; Adipose Tissue, White/metabolism ; *Androgens/administration &amp; dosage/adverse effects ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Blood Pressure ; *Dysbiosis/etiology/metabolism/microbiology/physiopathology ; Fatty Acids, Volatile/metabolism ; Gastrointestinal Microbiome ; Heart Rate ; *Hypertension/etiology/metabolism/microbiology/physiopathology ; *Maternal Exposure/adverse effects ; *Polycystic Ovary Syndrome/complications ; *Prenatal Exposure Delayed Effects/etiology/metabolism/microbiology/physiopathology ; Rats, Wistar ; *Testosterone/administration &amp; dosage/adverse effects/analogs &amp; derivatives ; }, abstract = {BACKGROUND: Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring.<br><br>RESULTS: The metabolic assessment revealed that adult PNA rats had increased body weight and increased mRNA expression of adipokines: adipocyte binding protein 2, adiponectin, and leptin in inguinal white adipose tissue. Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA animals. The fecal microbiota profile of PNA animals contained higher relative abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus, Clostridium. The PNA animals also had an increased relative abundance of bacteria associated with biosynthesis and elongation of unsaturated short chain fatty acids (SCFAs).<br><br>CONCLUSIONS: We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in metabolite production of short chain fatty acids. These results suggest that early-life exposure to hyperandrogenemia in daughters of women with PCOS may lead to long-term alterations in gut microbiota and cardiometabolic function.}, }
@article {pmid29467322, year = {2018}, author = {Uribe-Herranz, M and Bittinger, K and Rafail, S and Guedan, S and Pierini, S and Tanes, C and Ganetsky, A and Morgan, MA and Gill, S and Tanyi, JL and Bushman, FD and June, CH and Facciabene, A}, title = {Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12.}, journal = {JCI insight}, volume = {3}, number = {4}, pages = {}, pmid = {29467322}, issn = {2379-3708}, support = {P30 DK050306/DK/NIDDK NIH HHS/United States ; R01 CA219871/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Bacteria/drug effects/genetics/immunology/isolation &amp; purification ; CD8 Antigens/immunology/metabolism ; Cell Line, Tumor/transplantation ; Cohort Studies ; Dendritic Cells/drug effects/*immunology/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/drug effects/genetics/*immunology ; *Hematopoietic Stem Cell Transplantation ; Host Microbial Interactions/drug effects/*immunology ; Humans ; Immunotherapy, Adoptive/*methods ; Interleukin-12/antagonists &amp; inhibitors/genetics/*immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Neomycin/administration &amp; dosage ; Neoplasms/immunology/microbiology/*therapy ; T-Lymphocytes/immunology/transplantation ; Treatment Outcome ; Vancomycin/administration &amp; dosage ; }, abstract = {Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here, we report that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer. Depletion of bacteria with vancomycin decreased the rate of tumor growth in mice from The Jackson Laboratory receiving ACT, whereas treatment with neomycin and metronidazole had no effect, indicating the role of specific bacteria in host response. Vancomycin treatment induced an increase in systemic CD8α+ DCs, which sustained systemic adoptively transferred antitumor T cells in an IL-12-dependent manner. In subjects undergoing allogeneic hematopoietic cell transplantation, we found that oral vancomycin also increased IL-12 levels. Collectively, our findings demonstrate an important role played by the gut microbiota in the antitumor effectiveness of ACT and suggest potentially new avenues to improve response to ACT by altering the gut microbiota.}, }
@article {pmid29463339, year = {2018}, author = {Le, P and Nghiem, VT and Mullen, PD and Deshpande, A}, title = {Cost-Effectiveness of Competing Treatment Strategies for Clostridium difficile Infection: A Systematic Review.}, journal = {Infection control and hospital epidemiology}, volume = {39}, number = {4}, pages = {412-424}, pmid = {29463339}, issn = {1559-6834}, support = {K08 HS025026/HS/AHRQ HHS/United States ; R25 CA057712/CA/NCI NIH HHS/United States ; }, mesh = {*Anti-Bacterial Agents/economics/therapeutic use ; *Clostridium Infections/economics/therapy ; Cost of Illness ; Cost-Benefit Analysis ; *Fecal Microbiota Transplantation/economics/methods ; Humans ; }, abstract = {BACKGROUND Clostridium difficile infection (CDI) presents a substantial economic burden and is associated with significant morbidity. While multiple treatment strategies have been evaluated, a cost-effective management strategy remains unclear. OBJECTIVE We conducted a systematic review to assess cost-effectiveness analyses of CDI treatment and to summarize key issues for clinicians and policy makers to consider. METHODS We searched PubMed and 5 other databases from inception to August 2016. These searches were not limited by study design or language of publication. Two reviewers independently screened the literature, abstracted data, and assessed methodological quality using the Drummond and Jefferson checklist. We extracted data on study characteristics, type of CDI, treatment characteristics, and model structure and inputs. RESULTS We included 14 studies, and 13 of these were from high-income countries. More than 90% of these studies were deemed moderate-to-high or high quality. Overall, 6 studies used a decision-tree model and 7 studies used a Markov model. Cost of therapy, time horizon, treatment cure rates, and recurrence rates were common influential factors in the study results. For initial CDI, fidaxomicin was a more cost-effective therapy than metronidazole or vancomycin in 2 of 3 studies. For severe initial CDI, 2 of 3 studies found fidaxomicin to be the most cost-effective therapy. For recurrent CDI, fidaxomicin was cost-effective in 3 of 5 studies, while fecal microbiota transplantation (FMT) by colonoscopy was consistently cost-effective in 4 of 4 studies. CONCLUSIONS The cost-effectiveness of fidaxomicin compared with other pharmacologic therapies was not definitive for either initial or recurrent CDI. Despite its high cost, FMT by colonoscopy may be a cost-effective therapy for recurrent CDI. A consensus on model design and assumptions are necessary for future comparison of CDI treatment. Infect Control Hosp Epidemiol 2018;39:412-424.}, }
@article {pmid29463185, year = {2018}, author = {Bruno, G and Colangelo, L and Badiali, D and Minisola, S and Corazziari, ES and Gianni, W}, title = {Concomitant resolution through fecal microbiota transplantation of Clostridium difficile and OXA-48-producing Klebsiella pneumoniae.}, journal = {Infectious diseases (London, England)}, volume = {50}, number = {7}, pages = {565-566}, doi = {10.1080/23744235.2018.1442019}, pmid = {29463185}, issn = {2374-4243}, mesh = {*Clostridioides difficile ; Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Klebsiella pneumoniae ; Recurrence ; }, }
@article {pmid29460474, year = {2018}, author = {Mischke, M and Arora, T and Tims, S and Engels, E and Sommer, N and van Limpt, K and Baars, A and Oozeer, R and Oosting, A and Bäckhed, F and Knol, J}, title = {Specific synbiotics in early life protect against diet-induced obesity in adult mice.}, journal = {Diabetes, obesity &amp; metabolism}, volume = {20}, number = {6}, pages = {1408-1418}, pmid = {29460474}, issn = {1463-1326}, mesh = {Animals ; Anti-Obesity Agents/administration &amp; dosage/pharmacology ; *Bifidobacterium breve ; Blood Glucose/metabolism ; Body Constitution/physiology ; Body Weight/physiology ; Cholesterol/metabolism ; Diet, Western/adverse effects ; Female ; Gastrointestinal Microbiome/physiology ; Ileum/metabolism ; Lipid Metabolism/physiology ; Male ; Mice, Inbred C57BL ; Obesity/blood/*prevention &amp; control ; Phenotype ; Prebiotics/administration &amp; dosage ; Synbiotics/*administration &amp; dosage ; }, abstract = {AIMS: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health throughout life. Here, we determined how beneficial microbiome interventions in early life affect metabolic health in adulthood.<br><br>METHODS: Postnatal diets were supplemented with either prebiotics (scGOS/lcFOS) or synbiotics (scGOS/lcFOS with Bifidobacterium breve M-16&#x2009;V) until post-natal (PN) day 42 in a well-established rodent model for nutritional programming. Mice were subsequently challenged with a high-fat Western-style diet (WSD) for 8 weeks. Body weight and composition were monitored, as was gut microbiota composition at PN21, 42 and 98. Markers of glucose homeostasis, lipid metabolism and host transcriptomics of 6 target tissues were determined in adulthood (PN98).<br><br>RESULTS: Early life synbiotics protected mice against WSD-induced excessive fat accumulation throughout life, replicable in 2 independent European animal facilities. Adult insulin sensitivity and dyslipidaemia were improved and most pronounced changes in gene expression were observed in the ileum. We observed subtle changes in faecal microbiota composition, both in early life and in adulthood, including increased abundance of Bifidobacterium. Microbiota transplantation using samples collected from synbiotics-supplemented adolescent mice at PN42 to age-matched germ-free recipients did not transfer the beneficial phenotype, indicating that synbiotics-modified microbiota at PN42 is not sufficient to transfer long-lasting protection of metabolic health status.<br><br>CONCLUSION: Together, these findings show the potential and importance of timing of synbiotic interventions in early life during crucial microbiota development as a preventive measure to lower the risk of obesity and improve metabolic health throughout life.}, }
@article {pmid29460302, year = {2018}, author = {Pereira, GQ and Gomes, LA and Santos, IS and Alfieri, AF and Weese, JS and Costa, MC}, title = {Fecal microbiota transplantation in puppies with canine parvovirus infection.}, journal = {Journal of veterinary internal medicine}, volume = {32}, number = {2}, pages = {707-711}, pmid = {29460302}, issn = {1939-1676}, mesh = {Animals ; Diarrhea/therapy/*veterinary ; Dog Diseases/*therapy/virology ; Dogs ; Fecal Microbiota Transplantation/*veterinary ; Gastrointestinal Hemorrhage/therapy/veterinary ; Parvoviridae Infections/microbiology/therapy/*veterinary ; Parvovirus, Canine/classification ; Treatment Outcome ; }, abstract = {BACKGROUND: Diarrhea associated with parvovirus infection is common in dogs. Supportive care is the mainstay of treatment, but recovery may be prolonged and mortality rate can be high. Modification of the intestinal bacterial microbiota has been promising in human and veterinary medicine as an adjunctive treatment of various enteric diseases.<br><br>OBJECTIVES: To investigate the safety and efficacy of fecal microbiota transplantation (FMT) on the clinical recovery of puppies with acute hemorrhagic diarrhea syndrome.<br><br>ANIMALS: Sixty-six puppies with parvovirus infection were evaluated at 2 veterinary hospitals.<br><br>METHODS: Randomized clinical trial. Puppies were randomly distributed into 2 groups: standard treatment (STD) and standard treatment&#x2009;+&#x2009;FMT (STD&#x2009;+&#x2009;FMT). The STD puppies (n&#x2009;=&#x2009;33) received only treatment with IV fluids and antimicrobials and the STD&#x2009;+&#x2009;FMT puppies (n&#x2009;=&#x2009;33) received FMT in addition to standard treatment. For FMT, 10 g of feces from a healthy dog diluted in 10 mL of saline were administered rectally 6-12 hours post-admission.<br><br>RESULTS: Among survivors, treatment with FMT was associated with faster resolution of diarrhea (P&#x2009;<&#x2009;.001) and shorter hospitalization time (P&#x2009;=&#x2009;.001; median, 3 days in STD&#x2009;+&#x2009;FMT; median, 6 days in STD) compared to standard treatment. Mortality in STD was 36.4% (12/33) as compared to 21.2% (7/33) in puppies treated with FMT, but there was no statistical difference between groups (P&#x2009;=&#x2009;.174). Polymerase chain reaction indicated that all animals carried canine parvovirus, strain CPV-2b.<br><br>CONCLUSIONS: Fecal microbiota transplantation in parvovirus-infected puppies was associated with faster resolution of diarrhea.}, }
@article {pmid29454797, year = {2018}, author = {Tedesco, D and Thapa, M and Chin, CY and Ge, Y and Gong, M and Li, J and Gumber, S and Speck, P and Elrod, EJ and Burd, EM and Kitchens, WH and Magliocca, JF and Adams, AB and Weiss, DS and Mohamadzadeh, M and Grakoui, A}, title = {Alterations in Intestinal Microbiota Lead to Production of Interleukin 17 by Intrahepatic γδ T-Cell Receptor-Positive Cells and Pathogenesis of Cholestatic Liver Disease.}, journal = {Gastroenterology}, volume = {154}, number = {8}, pages = {2178-2193}, pmid = {29454797}, issn = {1528-0012}, support = {P30 AI050409/AI/NIAID NIH HHS/United States ; R01 AI136533/AI/NIAID NIH HHS/United States ; P51 OD011132/OD/NIH HHS/United States ; P51 RR000165/RR/NCRR NIH HHS/United States ; R01 AI070101/AI/NIAID NIH HHS/United States ; K01 DK109025/DK/NIDDK NIH HHS/United States ; R01 AI126890/AI/NIAID NIH HHS/United States ; R01 AI124680/AI/NIAID NIH HHS/United States ; }, mesh = {ATP Binding Cassette Transporter, Subfamily B/genetics ; Adult ; Aged ; Animals ; Bile Ducts/cytology/immunology/microbiology ; Cells, Cultured ; Cholangitis, Sclerosing/microbiology/pathology/surgery ; Cholestasis/immunology/microbiology/*pathology/surgery ; Disease Models, Animal ; End Stage Liver Disease/microbiology/pathology/surgery ; Female ; *Gastrointestinal Microbiome ; Hepatitis C, Chronic/pathology/surgery/virology ; Humans ; Interleukin-17/antagonists &amp; inhibitors/blood/immunology/*metabolism ; Intraepithelial Lymphocytes/*metabolism ; Lactobacillus gasseri/immunology ; Liver/cytology/immunology/microbiology/pathology ; Liver Cirrhosis/immunology/microbiology/*pathology/surgery ; Liver Transplantation ; Male ; Mice ; Mice, Knockout ; Middle Aged ; Receptors, Antigen, T-Cell, gamma-delta/antagonists &amp; inhibitors/metabolism ; Young Adult ; ATP-Binding Cassette Sub-Family B Member 4 ; }, abstract = {BACKGROUND &amp; AIMS: Variants at the ABCB4 or MDR2 locus, which encodes a biliary transport protein, are associated with a spectrum of cholestatic liver diseases. Exacerbation of liver disease has been linked to increased hepatic levels of interleukin (IL) 17, yet the mechanisms of this increase are not understood. We studied mice with disruption of Mdr2 to determine how defects in liver and alteration in the microbiota contribute to production of IL17 by intrahepatic γδ T cells.<br><br>METHODS: We performed studies with Mdr2[-/-] and littermate FVB/NJ (control) mice. IL17 was measured in serum samples by an enzyme-linked immunosorbent assay. Mice were injected with neutralizing antibodies against the &#x3b3;&#x3b4; T-cell receptor (TCR; anti-&#x3b3;&#x3b4; TCR) or mouse IL17A (anti-IL17A). Livers were collected and bacteria were identified in homogenates by culture procedures; TCR&#x3b3;&#x3b4;[+] cells were isolated by flow cytometry. Fecal samples were collected from mice and analyzed by 16S ribosomal DNA sequencing. Cells were stimulated with antibodies or bacteria, and cytokine production was measured. We obtained tissues from 10 patients undergoing liver transplantation for primary sclerosing cholangitis or chronic hepatitis C virus infection. Tissues were analyzed for cytokine production by &#x3b3;&#x3b4; TCR[+] cells.<br><br>RESULTS: Mdr2[-/-] mice had collagen deposition around hepatic bile ducts and periportal-bridging fibrosis with influx of inflammatory cells and increased serum levels of IL17 compared with control mice. Administration of anti-IL17A reduced hepatic fibrosis. Livers from Mdr2[-/-] mice had increased numbers of IL17A[+] &#x3b3;&#x3b4;TCR[+] cells-particularly of IL17A[+] V&#x3b3;6J&#x3b3;1 &#x3b3;&#x3b4; TCR[+] cells. Fecal samples from Mdr2[-/-] mice were enriched in Lactobacillus, and liver tissues were enriched in Lactobacillus gasseri compared with control mice. Mdr2[-/-] mice also had increased intestinal permeability. The &#x3b3;&#x3b4; TCR[+] cells isolated from Mdr2[-/-] livers produced IL17 in response to heat-killed L gasseri. Intraperitoneal injection of control mice with L gasseri led to increased serum levels of IL17 and liver infiltration by inflammatory cells; injection of these mice with anti-&#x3b3;&#x3b4; TCR reduced serum level of IL17. Intravenous injections of Mdr2[-/-] mice with anti-&#x3b3;&#x3b4; TCR reduced fibrosis; liver levels of IL17, and inflammatory cells; and serum levels of IL17. &#x3b3;&#x3b4;TCR[+] cells isolated from livers of patients with primary sclerosing cholangitis, but not hepatitis C virus infection, produced IL17.<br><br>CONCLUSIONS: In Mdr2[-/-] mice, we found development of liver fibrosis and inflammation to require hepatic activation of &#x3b3;&#x3b4; TCR[+] cells and production of IL17 mediated by exposure to L gasseri. This pathway appears to contribute to development of cholestatic liver disease in patients.}, }
@article {pmid29451873, year = {2018}, author = {Jones, EW and Carlson, JM}, title = {In silico analysis of antibiotic-induced Clostridium difficile infection: Remediation techniques and biological adaptations.}, journal = {PLoS computational biology}, volume = {14}, number = {2}, pages = {e1006001}, pmid = {29451873}, issn = {1553-7358}, mesh = {Adaptation, Biological ; Animals ; Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile ; Clostridium Infections/*physiopathology ; Computer Simulation ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces ; Gastrointestinal Microbiome ; Humans ; Mice ; Models, Theoretical ; Mutation ; Spores, Bacterial ; }, abstract = {In this paper we study antibiotic-induced C. difficile infection (CDI), caused by the toxin-producing C. difficile (CD), and implement clinically-inspired simulated treatments in a computational framework that synthesizes a generalized Lotka-Volterra (gLV) model with SIR modeling techniques. The gLV model uses parameters derived from an experimental mouse model, in which the mice are administered antibiotics and subsequently dosed with CD. We numerically identify which of the experimentally measured initial conditions are vulnerable to CD colonization, then formalize the notion of CD susceptibility analytically. We simulate fecal transplantation, a clinically successful treatment for CDI, and discover that both the transplant timing and transplant donor are relevant to the the efficacy of the treatment, a result which has clinical implications. We incorporate two nongeneric yet dangerous attributes of CD into the gLV model, sporulation and antibiotic-resistant mutation, and for each identify relevant SIR techniques that describe the desired attribute. Finally, we rely on the results of our framework to analyze an experimental study of fecal transplants in mice, and are able to explain observed experimental results, validate our simulated results, and suggest model-motivated experiments.}, }
@article {pmid29450831, year = {2018}, author = {Goldenberg, SD and Batra, R and Beales, I and Digby-Bell, JL and Irving, PM and Kellingray, L and Narbad, A and Franslem-Elumogo, N}, title = {Comparison of Different Strategies for Providing Fecal Microbiota Transplantation to Treat Patients with Recurrent Clostridium difficile Infection in Two English Hospitals: A Review.}, journal = {Infectious diseases and therapy}, volume = {7}, number = {1}, pages = {71-86}, pmid = {29450831}, issn = {2193-8229}, support = {BBS/E/F/00042733/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Fecal microbiota transplant (FMT) has emerged as a highly efficacious treatment for difficult cases of refractory and/or recurrent Clostridium difficile infection (CDI). There have been many well-conducted randomized controlled trials and thousands of patients reported in case series that describe success rates of approximately 90% following one or more FMT. Although the exact mechanisms of FMT have yet to be fully elucidated, replacement or restoration of a 'normal' microbiota (or at least a microbiota resembling those who have never had CDI) appears to have a positive effect on the gut dysbiosis that is thought to exist in these patients. Furthermore, despite being aesthetically unappealing, this 'ultimate probiotic' is a particularly attractive solution to a difficult problem that avoids repeated courses of antibiotics. The lack of clarity about the exact mechanism of action and the 'active ingredient' of FMT (e.g., individual or communities of bacteria, bacteriophage, or bioactive molecules such as bile acids) has hindered the ability to produce a standardized and well-characterized FMT product. There is no standard method to produce material for FMT, and there are a multitude of factors that can vary between institutions that offer this therapy. Only a few studies have directly compared clinical efficacy in groups of patients who have been treated with FMT prepared differently (e.g., fresh vs. frozen) or administered by different route (e.g., by nasojejunal tube, colonoscopy or by oral administration of encapsulated product). More of these studies should be undertaken to clarify the superiority or otherwise of these variables. This review describes the methods and protocols that two English NHS hospitals independently adopted over the same time period to provide FMT for patients with recurrent CDI. There are several fundamental differences in the methods used, including selection and testing of donors, procedures for preparation and storage of material, and route of administration. These methods are described in detail in this review highlighting differing practice. Despite these significant methodological variations, clinical outcomes in terms of cure rate appear to be remarkably similar for both FMT providers. Although both hospitals have treated only modest numbers of patients, these findings suggest that many of the described differences may not be critical factors in influencing the success of the procedure. As FMT is increasingly being proposed for a number of conditions other than CDI, harmonization of methods and techniques may be more critical to the success of FMT, and thus it will be important to standardize these as far as practically possible.}, }
@article {pmid29450212, year = {2018}, author = {Wang, T and Kraft, CS and Woodworth, MH and Dhere, T and Eaton, ME}, title = {Fecal Microbiota Transplant for Refractory Clostridium difficile Infection Interrupts 25-Year History of Recurrent Urinary Tract Infections.}, journal = {Open forum infectious diseases}, volume = {5}, number = {2}, pages = {ofy016}, pmid = {29450212}, issn = {2328-8957}, support = {UL1 TR002378/TR/NCATS NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; }, }
@article {pmid29449660, year = {2018}, author = {Shono, Y and van den Brink, MRM}, title = {Gut microbiota injury in allogeneic haematopoietic stem cell transplantation.}, journal = {Nature reviews. Cancer}, volume = {18}, number = {5}, pages = {283-295}, pmid = {29449660}, issn = {1474-1768}, support = {R01 AI101406/AI/NIAID NIH HHS/United States ; R01 HL069929/HL/NHLBI NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI100288/AI/NIAID NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/adverse effects ; Dysbiosis/etiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Graft vs Host Disease/etiology/*microbiology ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects/mortality ; Humans ; Infections/etiology/*microbiology ; Prebiotics ; Probiotics/pharmacology ; Transplantation, Homologous/*adverse effects/mortality ; }, abstract = {Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered to be the strongest curative immunotherapy for various malignancies (primarily, but not limited to, haematologic malignancies). However, application of allo-HSCT is limited owing to its life-threatening major complications, such as graft-versus-host disease (GVHD), relapse and infections. Recent advances in large-scale DNA sequencing technology have facilitated rapid identification of the microorganisms that make up the microbiota and evaluation of their interactions with host immunity in various diseases, including cancer. This has resulted in renewed interest regarding the role of the intestinal flora in patients with haematopoietic malignancies who have received an allo-HSCT and in whether the microbiota affects clinical outcomes, including GVHD, relapse, infections and transplant-related mortality. In this Review, we discuss the potential role of intestinal microbiota in these major complications after allo-HSCT, summarize clinical trials evaluating the microbiota in patients who have received allo-HSCT and discuss how further studies of the microbiota could inform the development of strategies that improve outcomes of allo-HSCT.}, }
@article {pmid29449093, year = {2019}, author = {Martínez-Ayala, P and González-Hernández, LA and Amador-Lara, F and Andrade-Villanueva, J and Ramos-Solano, M}, title = {Fecal microbiota transplantation for severe complicated C. difficile colitis in a patient with acquired immunodeficiency syndrome.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {84}, number = {1}, pages = {110-112}, doi = {10.1016/j.rgmx.2017.12.002}, pmid = {29449093}, issn = {2255-534X}, mesh = {Acquired Immunodeficiency Syndrome/*complications ; Adult ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*complications/diagnostic imaging/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; }, }
@article {pmid29447696, year = {2018}, author = {Smillie, CS and Sauk, J and Gevers, D and Friedman, J and Sung, J and Youngster, I and Hohmann, EL and Staley, C and Khoruts, A and Sadowsky, MJ and Allegretti, JR and Smith, MB and Xavier, RJ and Alm, EJ}, title = {Strain Tracking Reveals the Determinants of Bacterial Engraftment in the Human Gut Following Fecal Microbiota Transplantation.}, journal = {Cell host &amp; microbe}, volume = {23}, number = {2}, pages = {229-240.e5}, pmid = {29447696}, issn = {1934-6069}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 AT009708/AT/NCCIH NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; T32 GM087237/GM/NIGMS NIH HHS/United States ; }, mesh = {Biodiversity ; Clostridioides difficile/*growth &amp; development ; Clostridium Infections/*prevention &amp; control/therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Models, Biological ; Recurrence ; Secondary Prevention/*methods ; }, abstract = {Fecal microbiota transplantation (FMT) from healthy donor to patient is a treatment for microbiome-associated diseases. Although the success of FMT requires donor bacteria to engraft in the patient's gut, the forces governing engraftment in humans are unknown. Here we use an ongoing clinical experiment, the treatment of recurrent Clostridium difficile infection, to uncover the rules of engraftment in humans. We built a statistical model that predicts which bacterial species will engraft in a given host, and developed Strain Finder, a method to infer strain genotypes and track them over time. We find that engraftment can be predicted largely from the abundance and phylogeny of bacteria in the donor and the pre-FMT patient. Furthermore, donor strains within a species engraft in an all-or-nothing manner and previously undetected strains frequently colonize patients receiving FMT. We validated these findings for metabolic syndrome, suggesting that the same principles of engraftment extend to other indications.}, }
@article {pmid29446866, year = {2018}, author = {Woodworth, MH and Kraft, CS and Meredith, EJ and Mehta, AK and Wang, T and Mamo, YT and Dhere, T and Sitchenko, KL and Patzer, RE and Friedman-Moraco, RJ}, title = {Tacrolimus concentration to dose ratio in solid organ transplant patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {20}, number = {2}, pages = {e12857}, pmid = {29446866}, issn = {1399-3062}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; }, mesh = {Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Immunosuppressive Agents/*blood/pharmacokinetics ; Organ Transplantation/*adverse effects ; Retrospective Studies ; Tacrolimus/*blood/pharmacokinetics ; }, abstract = {Fecal microbiota transplantation (FMT) is increasingly being performed for Clostridium difficile infection in solid organ transplant (SOT) patients; however, little is known about the potential pharmacokinetic or pharmacomicrobial effects this may have on tacrolimus levels. We reviewed the medical records of 10 SOT patients from September 2012-December 2016 who were taking tacrolimus at time of FMT for recurrent C. difficile infection. We compared the differences in tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months after FMT. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/kg/d) was -17.65 (95% CI -1.25 to 0.58) (ng/mL)/(mg/kg/d), P-value .43 by Wilcoxon signed-rank test. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/d) was -0.33 (95% CI -1.25 to 0.58) (ng/mL)/(mg/d), P-value .28 by Wilcoxon signed-rank test. Of these patients, 2/10 underwent allograft biopsy for allograft dysfunction in the year after FMT, with no evidence of allograft rejection on pathology. These preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for SOT patients however further study in randomized trials is needed.}, }
@article {pmid29446158, year = {2019}, author = {Smith, LM and Parr-Brownlie, LC}, title = {A neuroscience perspective of the gut theory of Parkinson's disease.}, journal = {The European journal of neuroscience}, volume = {49}, number = {6}, pages = {817-823}, doi = {10.1111/ejn.13869}, pmid = {29446158}, issn = {1460-9568}, support = {17-284//Health Research Council of New Zealand/International ; PG15-41//Neurological Foundation of New Zealand/International ; }, mesh = {Biomarkers/metabolism ; Brain/metabolism/*physiopathology ; Gastrointestinal Microbiome/*physiology ; Humans ; *Neurosciences/methods ; Parkinson Disease/*physiopathology ; alpha-Synuclein/metabolism ; }, abstract = {Parkinson's disease is caused by complex interactions between environmental factors and a genetic predisposition. Environmental factors include exposure to pesticides and toxins, heavy metals and accumulation of iron and/or manganese in the brain. However, accumulating evidence indicates that gut-brain health and function are impaired in Parkinson's disease, often a decade before motor symptoms are diagnosed. We present the gut-brain theory of Parkinson's disease and summarise the peripheral and central nervous system pathology, gastrointestinal symptoms experienced by many Parkinson's patients, the route by which gut-brain dysfunction may occur and changes in gut microbiota that are associated with disease expression. Finally, we consider future gut-based treatments to prevent or slow down the progression of Parkinson's disease and explore whether this knowledge may highlight biomarkers to be included in complex algorithms in the future to assess a person's risk of developing Parkinson's disease.}, }
@article {pmid29445178, year = {2018}, author = {Sun, YY and Li, M and Li, YY and Li, LX and Zhai, WZ and Wang, P and Yang, XX and Gu, X and Song, LJ and Li, Z and Zuo, XL and Li, YQ}, title = {The effect of Clostridium butyricum on symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {2964}, pmid = {29445178}, issn = {2045-2322}, mesh = {Adult ; Clostridium butyricum/*physiology ; Diarrhea/microbiology/*therapy ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Male ; Middle Aged ; Placebos ; Probiotics/*therapeutic use ; Prospective Studies ; Quality of Life ; Treatment Outcome ; }, abstract = {Irritable bowel syndrome (IBS) is a common disorder in gastrointestinal system and impairs the quality of life of the patients. Clostridium butyricum (CB) is a probiotics that has been used in several gastrointestinal diseases. The efficacy of CB in treating IBS is still unknown. This prospective, multi-centre, randomized, double-blind, placebo-controlled trial aimed to assess the efficacy and safety of CB in treating diarrhea-predominant IBS (IBS-D) and analyze the fecal microbiota after treatment. Two hundred patients with IBS-D were recruited and were given CB or placebo for 4 weeks. End points included change from baseline in IBS symptoms, quality of life, stool consistency and frequency. Compared with placebo, CB is effective in improving the overall IBS-D symptoms (-62.12 ± 74.00 vs. -40.74 ± 63.67, P = 0.038) as well as quality of life (7.232 ± 14.06 vs. 3.159 ± 11.73, P = 0.032) and stool frequency (-1.602 ± 1.416 vs. -1.086 ± 1.644, P = 0.035). The responder rates are found higher in CB compared with the placebo (44.76% vs. 30.53%, P = 0.042). The change in fecal microbiota was analyzed and function pathways of CB in treating IBS-D were predicted. In conclusion, CB improves overall symptoms, quality of life and stool frequency in IBS-D patients and is considered to be used as a probiotics in treating IBS-D clinically.}, }
@article {pmid29441452, year = {2018}, author = {Zhang, X and Tian, H and Gu, L and Nie, Y and Ding, C and Ge, X and Yang, B and Gong, J and Li, N}, title = {Long-term follow-up of the effects of fecal microbiota transplantation in combination with soluble dietary fiber as a therapeutic regimen in slow transit constipation.}, journal = {Science China. Life sciences}, volume = {61}, number = {7}, pages = {779-786}, doi = {10.1007/s11427-017-9229-1}, pmid = {29441452}, issn = {1869-1889}, mesh = {Adult ; Combined Modality Therapy ; Constipation/physiopathology/*therapy ; Defecation ; Dietary Fiber/*therapeutic use ; *Fecal Microbiota Transplantation ; Female ; Follow-Up Studies ; Gastrointestinal Transit ; Humans ; Male ; Middle Aged ; Pectins/*therapeutic use ; Treatment Outcome ; }, abstract = {As some studies have reported that strategies targeting the gut microbiota such as fecal microbiota transplantation (FMT) with or without other microecological therapy might have efficacy in treating slow transit constipation (STC), we conducted a single-center, open-label trial to study the long-term effect of FMT combined with soluble dietary fiber (pectin) on STC. Thirty-one adult patients with STC were enrolled into the trial. Patients received 6-day FMT procedures repeatedly for the first 3 months and soluble dietary fiber (pectin) daily during the follow-up. The rate of clinical remission and improvement, stool consistency, the Wexner constipation scale, and assessment of constipation-related symptoms were evaluated at week 4 and 1 year later. The clinical remission and improvement rates at week 4 were 69.0% (20/29) and 75.9% (22/29), respectively. At the end of the study, 48.3% (14/29) of patients continued to have at least three complete spontaneous bowel movements per week and 58.6% (17/29) of patients showed clinical improvements. Stool consistency, the Wexner constipation scale, and constipation symptoms improved both at short-term and long-term follow-up. The results indicated that FMT in combination with soluble dietary fiber (pectin) had both short-term and long-term efficacy in treating STC.}, }
@article {pmid29441063, year = {2018}, author = {Lu, Y and Li, X and Liu, S and Zhang, Y and Zhang, D}, title = {Toll-like Receptors and Inflammatory Bowel Disease.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {72}, pmid = {29441063}, issn = {1664-3224}, support = {R21 CA176698/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Disease Susceptibility ; Gastrointestinal Microbiome/immunology ; Genetic Predisposition to Disease ; Homeostasis ; Humans ; Immunity, Innate ; Immunity, Mucosal ; Immunomodulation ; Inflammatory Bowel Diseases/diagnosis/*etiology/*metabolism/therapy ; Signal Transduction ; Toll-Like Receptors/*metabolism ; }, abstract = {Inflammatory bowel disease (IBD) is one relapsing and lifelong disease that affects millions of patients worldwide. Increasing evidence has recently highlighted immune-system dysfunction, especially toll-like receptors (TLRs)-mediated innate immune dysfunction, as central players in the pathogenesis of IBD. TLRs and TLR-activated signaling pathways are involved not only in the pathogenesis but also in the efficacy of treatment of IBD. By understanding these molecular mechanisms, we might develop a strategy for relieving the experience of long-lasting suffering of those patients and improving their quality of life. The purpose of this review article is to summarize the potential mechanisms of TLR signaling pathways in IBD and the novel potential therapeutic strategies against IBD.}, }
@article {pmid29440324, year = {2018}, author = {Shin, EC and Jeong, SH}, title = {Natural History, Clinical Manifestations, and Pathogenesis of Hepatitis A.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {8}, number = {9}, pages = {}, pmid = {29440324}, issn = {2157-1422}, mesh = {Acute Disease ; Disease Progression ; Hepatitis A/complications/*pathology ; Hepatitis A Vaccines/therapeutic use ; Hepatitis A virus/immunology ; Humans ; Liver/*physiopathology ; Liver Failure, Acute/*diagnosis/virology ; *Liver Transplantation ; Risk Factors ; }, abstract = {Hepatitis A virus (HAV) is transmitted by the fecal-oral route and is a major cause of acute viral hepatitis. The clinical manifestations of HAV infection range from asymptomatic infection to acute liver failure (ALF), but do not include progression to chronic hepatitis. Risk factors for severe acute hepatitis A are older age (>40 years) and preexisting liver disease. Some patients may show atypical clinical features such as relapsing hepatitis, prolonged cholestasis, or extrahepatic manifestations. Almost all hepatitis A patients spontaneously recover with supportive care. However, in the case of ALF (<1%), intensive care and urgent decision on liver transplantation are required. Liver injury during hepatitis A is not directly caused by HAV but is known to be caused by immune-mediated mechanisms. In this review, the natural history and clinical manifestations of hepatitis A are described. In addition, mechanisms of immunopathogenesis in hepatitis A are discussed.}, }
@article {pmid29438346, year = {2018}, author = {Wang, C and Zaheer, M and Bian, F and Quach, D and Swennes, AG and Britton, RA and Pflugfelder, SC and de Paiva, CS}, title = {Sjögren-Like Lacrimal Keratoconjunctivitis in Germ-Free Mice.}, journal = {International journal of molecular sciences}, volume = {19}, number = {2}, pages = {}, pmid = {29438346}, issn = {1422-0067}, support = {P30 CA125123/CA/NCI NIH HHS/United States ; T32 AI053831/AI/NIAID NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; P30 EY002520/EY/NEI NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; R01 EY026893/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology ; Fecal Microbiota Transplantation ; Female ; Germ-Free Life/*immunology ; Homeodomain Proteins/genetics/metabolism ; Immunity, Innate ; Interferon-gamma/metabolism ; Keratoconjunctivitis/immunology/*microbiology/therapy ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; }, abstract = {Commensal bacteria play an important role in the formation of the immune system but their role in the maintenance of immune homeostasis at the ocular surface and lacrimal gland remains poorly understood. This study investigated the eye and lacrimal gland phenotype in germ-free and conventional C57BL/6J mice. Our results showed that germ-free mice had significantly greater corneal barrier disruption, greater goblet cell loss, and greater total inflammatory cell and CD4[+] T cell infiltration within the lacrimal gland compared to the conventionally housed group. A greater frequency of CD4[+]IFN-γ[+] cells was observed in germ-free lacrimal glands. Females exhibited a more severe phenotype compared to males. Adoptive transfer of CD4[+] T cells isolated from female germ-free mice into RAG1KO mice transferred Sjögren-like lacrimal keratoconjunctivitis. Fecal microbiota transplant from conventional mice reverted dry eye phenotype in germ-free mice and decreased CD4[+]IFN-γ[+] cells to levels similar to conventional C57BL/6J mice. These findings indicate that germ-free mice have a spontaneous lacrimal keratoconjunctivitis similar to that observed in Sjögren syndrome patients and demonstrate that commensal bacteria function in maintaining immune homeostasis on the ocular surface. Thus, manipulation of intestinal commensal bacteria has the potential to become a novel therapeutic approach to treat Sjögren Syndrome.}, }
@article {pmid29432297, year = {2018}, author = {McClave, SA and Patel, J and Bhutiani, N}, title = {Should fecal microbial transplantation be used in the ICU?.}, journal = {Current opinion in critical care}, volume = {24}, number = {2}, pages = {105-111}, doi = {10.1097/MCC.0000000000000489}, pmid = {29432297}, issn = {1531-7072}, mesh = {Critical Illness/*therapy ; Dysbiosis/immunology/physiopathology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/immunology/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; *Intensive Care Units ; Multiple Organ Failure/immunology/*prevention &amp; control ; Practice Guidelines as Topic ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Maintaining gut barrier defenses, modulating immune responses, and supporting the role of commensal microbiota are major factors influencing outcome in critical illness. Of these, maintaining a commensal 'lifestyle' and preventing the emergence of a virulent pathobiome may be most important in reducing risk of infection and multiple organ failure.<br><br>RECENT FINDINGS: The polymeric formulas utilized for enteral nutrition in the ICU are absorbed high in the gastrointestinal tract and may not reach the microbial burden in the cecum where their effect is most needed. The provision of a few select probiotic organisms may be insufficient to refaunate the gut and establish a 'recovery pattern,' propelling the patient toward health and homeostasis. Use of fecal microbial transplantation (FMT) appears to be a more successful strategy for replenishing the intestinal microbiome and maintaining its commensal phenotypic expression.<br><br>SUMMARY: FMT has become an attractive option to mitigate multiple organ dysfunction in the ICU. This article discusses the physiology, rationale, early experience, and expectations for such therapy in the critically ill patient.}, }
@article {pmid29431777, year = {2018}, author = {Su, A and Yang, W and Zhao, L and Pei, F and Yuan, B and Zhong, L and Ma, G and Hu, Q}, title = {Flammulina velutipes polysaccharides improve scopolamine-induced learning and memory impairment in mice by modulating gut microbiota composition.}, journal = {Food &amp; function}, volume = {9}, number = {3}, pages = {1424-1432}, doi = {10.1039/c7fo01991b}, pmid = {29431777}, issn = {2042-650X}, mesh = {Animals ; Bacteria/classification/drug effects/genetics/isolation &amp; purification ; Cognitive Dysfunction/*drug therapy/*microbiology/psychology ; Feces/microbiology ; Flammulina/*chemistry ; Gastrointestinal Microbiome/*drug effects ; Humans ; Interleukin-10/genetics/metabolism ; Interleukin-1beta/genetics/metabolism ; Interleukin-6/genetics/metabolism ; Male ; Maze Learning/drug effects ; Memory/drug effects ; Mice ; Mice, Inbred C57BL ; Plant Extracts/*administration &amp; dosage ; Polysaccharides/*administration &amp; dosage ; Scopolamine/*administration &amp; dosage ; Tumor Necrosis Factor-alpha/genetics/metabolism ; }, abstract = {Flammulina velutipes polysaccharides (FVP) have been proved to be effective in improving learning and memory impairment in mice. However, their underlying mechanism remains unclear. The aim of this study was to investigate the relationship between memory improvement and gut microbiota regulation of FVP. The results showed a significant decrease in the relative abundances of Clostridia and Bacilli but a significant increase in Bacteroidia, Erysipelotrichia and Actinobacteria in the FVP-treated group versus the control group. Fecal microbiota transplantation of mice with 'FVP microbiota' derived from FVP-fed mice resulted in improved learning and memory function compared to colonization with 'common microbiota' derived from control individuals. FVP and 'FVP microbiota' significantly increased the numbers of platform crossings and the swimming distance of mice in the probe test and decreased the escape latency and total swimming distance of mice in the hidden platform test. Moreover, FVP and 'FVP microbiota' regulated cytokines, such as IL-1β, TNF-α, IL-6 and IL-10, suggesting a mechanism involving the suppression of neuroinflammation. This study indicated that the regulation of the gut microbiome may have a causal role in improving scopolamine-induced impairment of learning and memory.}, }
@article {pmid29430228, year = {2017}, author = {Adamski, JK and Jäschke, BB and Uusitalo-Seppälä, RS and Moilanen, KVJ and Pehkonen, AV and Weigl, W}, title = {Routine Treatment-Resistant Clostridium difficile Infection during Recovery from Myxedema.}, journal = {Case reports in gastroenterology}, volume = {11}, number = {3}, pages = {748-754}, pmid = {29430228}, issn = {1662-0631}, abstract = {Development of the extreme form of hypothyroidism defined as myxedema is very rare. Acute symptoms and their management have been described in detail previously. However, not much attention has been devoted to therapeutic challenges that are faced in the recovery phase of the treatment, especially pertaining to the gastrointestinal system. The link between myxedema and the appearance of severe Clostridium difficile infection (CDI) has not been established so far. A 61-year-old woman with no significant medical record was admitted to hospital because of infected heel pressure and thyroid dysfunction. A week later, due to hypothermia, hypotension, and unconsciousness, she was transferred to the intensive care unit. The clinical picture and the results of laboratory tests confirmed diagnosis of myxedema. After the introduction of resuscitative measures and hormonal substitution, patient's condition stabilized within 10 days. Due to concomitant sepsis, initially piperacillin/tazobactam and later cefuroxime were administered. After 20 days of antibiotic therapy, the patient developed CDI that was resistant to the routine mode of treatment. The clinical recovery was achieved only after a fecal microbiota transplantation procedure. The function of the digestive tract in myxedema is disturbed by gastric achlorydia and reduced peristalsis, which in turn can predispose the small intestine to overgrowth of bacteria. The use of antibiotics can additionally decrease the intestinal bacterial diversity, favoring the overgrowth of Clostridium difficile. The authors conclude that myxedema may increase the likelihood of a treatment-resistant form of CDI that requires the implementation of fecal microbiota transplantation.}, }
@article {pmid29429468, year = {2018}, author = {Gan, X and Li, J}, title = {[Research advances in necrotizing enterocolitis in neonates].}, journal = {Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics}, volume = {20}, number = {2}, pages = {164-168}, pmid = {29429468}, issn = {1008-8830}, mesh = {Abdomen/diagnostic imaging ; Enterocolitis, Necrotizing/diagnostic imaging/etiology/*prevention &amp; control/therapy ; Humans ; Infant, Newborn ; Intestines/microbiology ; }, abstract = {Necrotizing enterocolitis (NEC) is a catastrophic disease caused by a variety of factors in neonates, especially preterm infants. Severe NEC has a high fatality rate, and most survivors may face short- and long-term adverse prognosis. Risk factors for NEC include preterm birth, non-breastfeeding, microbial abnormalities in the digestive tract, and ischemia-reperfusion injury. High-resolution abdominal ultrasound helps with the early diagnosis of NEC. The preventive measures for NEC include protecting the intestinal mucosa through nutritional intervention, interfering with intestinal injury signals, changing intestinal microflora, and performing early minimal enteral nutrition. This disease progresses rapidly, and there are still no effective measures. Supportive care is mainly used for the treatment of this disease, and patients in severe conditions may need surgical treatment. Celastrol, lipopolysaccharide, and fecal transplantation help with the treatment of NEC, but further studies are needed to confirm their clinical effects.}, }
@article {pmid29428498, year = {2018}, author = {Samarkos, M and Mastrogianni, E and Kampouropoulou, O}, title = {The role of gut microbiota in Clostridium difficile infection.}, journal = {European journal of internal medicine}, volume = {50}, number = {}, pages = {28-32}, doi = {10.1016/j.ejim.2018.02.006}, pmid = {29428498}, issn = {1879-0828}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/*microbiology/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Proton Pump Inhibitors/therapeutic use ; }, abstract = {Clostridium difficile infection has emerged as a major health problem. Because it is a spore-forming microorganism, C. difficile is difficult to eradicate and recurrences of the infection are frequent. The strong association of CDI with prior use of antibiotics led to the recognition that disturbances in the gut microbiota apparently plays a central role in CDI. Except for antibiotics, several other risk factors for CDI have been recognised, such as advanced age and use of proton pump inhibitors. The common characteristic of these factors is that they are associated with changes in the composition of gut microbiota. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with reduced microbiota diversity. C. difficile infection per se seems to be associated with changes in the representation of specific microbial populations (e.g. taxa) which either may act protectively against C. difficile colonization of the gut or may increase susceptibility for C. difficile infection. Therapeutic gut microbiota manipulation can be achieved by faecal microbiota transplantation, which is highly effective for the treatment of CDI.}, }
@article {pmid29427903, year = {2018}, author = {Battson, ML and Lee, DM and Weir, TL and Gentile, CL}, title = {The gut microbiota as a novel regulator of cardiovascular function and disease.}, journal = {The Journal of nutritional biochemistry}, volume = {56}, number = {}, pages = {1-15}, doi = {10.1016/j.jnutbio.2017.12.010}, pmid = {29427903}, issn = {1873-4847}, mesh = {Aging ; Animals ; Anti-Bacterial Agents/chemistry ; Atherosclerosis/complications ; Bile Acids and Salts/metabolism ; Cardiovascular Diseases/*microbiology ; Cardiovascular System/*microbiology ; Diet ; Dysbiosis ; Exercise ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Hypertension/complications ; Inflammation ; Lipopolysaccharides/metabolism ; Methylamines/metabolism ; Mice ; Obesity/microbiology ; Peptidoglycan/metabolism ; Prebiotics ; Probiotics ; Risk Factors ; Sedentary Behavior ; Vascular Diseases/complications ; }, abstract = {The gut microbiome has emerged as a critical regulator of human physiology. Deleterious changes to the composition or number of gut bacteria, commonly referred to as gut dysbiosis, has been linked to the development and progression of numerous diet-related diseases, including cardiovascular disease (CVD). Most CVD risk factors, including aging, obesity, certain dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites that may facilitate the development of CVD. The aim of the current review is to summarize the available data regarding the role of the gut microbiome in regulating CVD function and disease processes. Particular emphasis is placed on nutrition-related alterations in the microbiome, as well as the underlying cellular mechanisms by which the microbiome may alter CVD risk.}, }
@article {pmid29426057, year = {2018}, author = {Stallmach, A and Anttila, VJ and Hell, M and Gwynn, S and Merino-Amador, P and Petrosillo, N and Ráčil, Z and Warren, T and Wenisch, C and Wilcox, M}, title = {Inflammatory bowel disease and Clostridium difficile infection: contrasting views of international clinical professionals.}, journal = {Zeitschrift fur Gastroenterologie}, volume = {}, number = {}, pages = {}, doi = {10.1055/s-0044-100045}, pmid = {29426057}, issn = {1439-7803}, abstract = {INTRODUCTION: In patients with inflammatory bowel disease (IBD), Clostridium difficile infection (CDI) is a risk factor for both morbidity and mortality. Currently, appropriate management is unclear. Guidance on best practice in the diagnosis and treatment of CDI in IBD patients is therefore needed.<br><br>METHODS: A multidisciplinary group of clinicians involved in the treatment of patients with IBD and CDI developed 27 consensus statements. Respondents were asked to rate their agreement with each statement using a 4-point Likert scale. A modified Delphi methodology was used to review responses of 442 physicians from different specialties (including infectious disease specialists [n&#x200a;=&#x200a;104], microbiologists [n&#x200a;=&#x200a;95], and gastroenterologists [n&#x200a;=&#x200a;73]). A threshold of 75&#x200a;% agreement was predefined as consensus.<br><br>RESULTS: Consensus was achieved for 17 of the 27 statements. Unprompted recognition of risk factors for CDI was low. Intensification of immunosuppressive therapy in the absence of clinical improvement was controversial. Clear definitions of treatment failure of antibiotic therapy in CDI and recurrence of CDI in IBD are needed. Respondents require further clarity regarding the place of fecal microbiota transplantation in CDI patients with IBD. Differences were observed between the perceptions of microbiologists and gastroenterologists, as well as between countries.<br><br>CONCLUSIONS: Different perceptions both between specialties and geographical locations complicate the development of an internationally accepted algorithm for the diagnosis and treatment of CDI in patients with IBD. This study highlights the need for future studies in this area.}, }
@article {pmid29422809, year = {2018}, author = {Nanki, K and Mizuno, S and Matsuoka, K and Ono, K and Sugimoto, S and Kiyohara, H and Arai, M and Nakashima, M and Takeshita, K and Saigusa, K and Senoh, M and Fukuda, T and Naganuma, M and Kato, H and Suda, W and Hattori, M and Kanai, T}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection in a patient with ulcerative colitis.}, journal = {Intestinal research}, volume = {16}, number = {1}, pages = {142-146}, pmid = {29422809}, issn = {1598-9100}, abstract = {Fecal microbiota transplantation (FMT) has been reported as a safe and effective therapy in patients with refractory and recurrent Clostridium difficile infection (CDI). FMT has also been reported as a promising therapy in patients with ulcerative colitis (UC). Both, CDI and UC, are believed to be caused by dysbiosis, such as altered compositions or decreased diversity of the intestinal microbiota. This report describes a patient with UC in remission with a second recurrent episode of CDI, who was treated with FMT. A single FMT performed via colonoscopy completely resolved the patient's diarrhea and eradicated C. difficile bacteriologically without any severe complications. Molecular biological analysis of the patient's fecal microbiota showed that FMT could dramatically change the altered composition of intestinal microbiota and restore its diversity. Despite the restoration of the intestinal microbiota, FMT could not prevent a relapse of UC in this patient. However, it improved the intestinal symptoms of CDI and could prevent further recurrences of CDI.}, }
@article {pmid29422802, year = {2018}, author = {Midha, V and Mahajan, R and Mehta, V and Narang, V and Singh, A and Kaur, K and Sood, A}, title = {Efficacy and safety of the adalimumab biosimilar Exemptia as induction therapy in moderate-to-severe ulcerative colitis.}, journal = {Intestinal research}, volume = {16}, number = {1}, pages = {83-89}, pmid = {29422802}, issn = {1598-9100}, abstract = {BACKGROUND/AIMS: Data on the efficacy and safety of the adalimumab biosimilar Exemptia are limited.<br><br>METHODS: Patients with moderate-to-severe active steroid-refractory ulcerative colitis (UC) treated at Dayanand Medical College and Hospital, India were offered cyclosporine A, biologicals or biosimilars, or surgery. A retrospective analysis was conducted on patients who were treated with the adalimumab biosimilar, Exemptia. These patients were administered an induction dosing schedule of 160 mg Exemptia at week 0, 80 mg at week 2, and then 40 mg every other week from week 4 to 8. The clinical response and remission were assessed at week 8 using Mayo score.<br><br>RESULTS: A total of 29 patients (62.1% male; mean age, 34.9 &#xb1; 9.7 years) with moderate-to-severe steroid-refractory active UC (mean disease duration, 6.3&#xb1;5.1 years; pancolitis in 9 patients [31.1%]; left-sided colitis in 20 patients [68.9%]) were treated with the Exemptia induction dosing schedule. The mean Mayo score at presentation was 8.2&#xb1;1.4. At week 8, clinical response was observed in 7 patients (24.1%), whereas clinical remission was observed only in 1 patient (3.5%). Among the non-responders (n=21), 4 patients required colectomy, 1 died, 1 was lost to follow-up, 10 were offered fecal microbiota transplant, 3 were administered infliximab, and 2 patients were administered cyclosporine and tacrolimus, respectively. Four patients (13.8%) developed extrapulmonary tuberculosis.<br><br>CONCLUSIONS: The adalimumab biosimilar Exemptia has limited efficacy for the attainment of clinical response and remission in moderate-to-severe steroid-refractory UC, with a significant risk of acquisition or reactivation of tuberculosis in developing countries such as India.}, }
@article {pmid29417924, year = {2018}, author = {Kates, AE and Tischendorf, JS and Schweizer, M and Herwaldt, L and Samore, M and Dukes, KC and Gerding, DN and Diekema, DJ and Safdar, N}, title = {Research Agenda for Microbiome Based Research for Multidrug-resistant Organism Prevention in the Veterans Health Administration System.}, journal = {Infection control and hospital epidemiology}, volume = {39}, number = {2}, pages = {202-209}, doi = {10.1017/ice.2017.311}, pmid = {29417924}, issn = {1559-6834}, support = {IP1 HX001993/HX/HSRD VA/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; }, mesh = {Congresses as Topic ; Dietary Supplements/microbiology ; Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Humans ; Interprofessional Relations ; Microbiota ; Research ; *Research Design ; United States ; *United States Department of Veterans Affairs ; }, }
@article {pmid29413214, year = {2018}, author = {Moore, SC}, title = {Clostridium difficile: More Challenging than Ever.}, journal = {Critical care nursing clinics of North America}, volume = {30}, number = {1}, pages = {41-53}, doi = {10.1016/j.cnc.2017.10.004}, pmid = {29413214}, issn = {1558-3481}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*diagnosis/*drug therapy/epidemiology ; Cross Infection ; Drug Resistance, Microbial ; *Fecal Microbiota Transplantation ; Humans ; Risk Factors ; United States/epidemiology ; }, abstract = {Clostridium difficile infection is not new, but it is posing more problems than ever before, described by the Centers for Disease Control and Prevention as an urgent threat. Its pathophysiology allows C difficile to be very difficult to manage, both within the hospital environment and in a patient's body. This article reviews clinical manifestations of the infection, outlines both medical and surgical treatment options, and discusses risk factors and predictors. Implications for nurses are thoroughly described. The epidemic proportion of C difficile infection gives cause for serious concern, especially for vulnerable populations, such as adults over age 65.}, }
@article {pmid29411990, year = {2018}, author = {Shawcross, DL}, title = {Diagnosis and management of hepatic encephalopathy.}, journal = {British journal of nursing (Mark Allen Publishing)}, volume = {27}, number = {Sup3}, pages = {S7-S13}, doi = {10.12968/bjon.2018.27.Sup3.S7}, pmid = {29411990}, issn = {0966-0461}, mesh = {Algorithms ; Hepatic Encephalopathy/classification/*diagnosis/*therapy ; Humans ; }, abstract = {Overt and covert hepatic encephalopathy (HE) are debilitating complications of cirrhosis. HE results in a poor quality of life for patients and their caregivers and, unless there is access to liver transplantation, the prognosis is poor. The development of overt HE is often unpredictable, and its management, particularly in the ward, remains challenging. There is an urgent need for novel approaches to treat HE. Until recently, therapies for this complication were disappointing, with frequently intolerable side effects such as diarrhoea and faecal incontinence. However, a non-absorbable antibiotic, rifaximin, * has been approved for the prevention of recurrent overt HE. It aims to reduce hospitalisation and resource use, as well as improve patients' quality of life. This article describes the practical aspects of diagnosing, classifying and managing HE. It reviews the pharmacological options for the treatment and prophylaxis of overt HE, and explores the evidence base demonstrating that rifaximin reduces the recurrence of overt HE.}, }
@article {pmid29411989, year = {2018}, author = {Ponte, A and Pinho, R and Mota, M and Silva, J and Vieira, N and Oliveira, R and Rodrigues, J and Sousa, M and Sousa, I and Carvalho, J}, title = {Fecal microbiota transplantation in refractory or recurrent Clostridium difficile infection: a real-life experience in a non-academic center.}, journal = {Revista espanola de enfermedades digestivas}, volume = {110}, number = {5}, pages = {311-315}, doi = {10.17235/reed.2018.5099/2017}, pmid = {29411989}, issn = {1130-0108}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {AIM: this study aimed to describe the efficacy and safety of fecal microbiota transplantation (FMT) for the treatment of refractory and recurrent Clostridium difficile infection (CDI).<br><br>METHODS: this was an observational study of patients with refractory or recurrent CDI treated with FMT between June 2014 and January 2017. Primary and secondary outcomes were the resolution of diarrhea without CDI recurrence within two months after one or more FMT. A descriptive analysis was performed.<br><br>RESULTS: thirty-four FMT were performed in 28 patients, 88.2% (n = 30) using an upper route with a gastroscopy and 11.8% (n = 4) with colonoscopy; 50% (n = 17) of FMT were due to recurrent CDI and 50% (n = 17) were due to refractory CDI. The overall cure rate of upper FMT was 87.5% (21/24) and 100% (4/4) when colonoscopy was performed. A cure was achieved after one FMT in 88% (22/25) of cases and after two or more FMT in 8% (2/25) of cases, resulting in an overall cure rate of 96% (24/25). No severe adverse events were reported.<br><br>CONCLUSION: FMT constitutes an effective and safe approach for the management of refractory and recurrent CDI, with an overall cure rate of 96% and no reported severe adverse events.}, }
@article {pmid29408638, year = {2018}, author = {Allamneni, C and Nelson, G and Weber, F}, title = {A Rare Cause of Recurrent Abdominal Pain and Diarrhea.}, journal = {Gastroenterology}, volume = {155}, number = {2}, pages = {e11-e12}, doi = {10.1053/j.gastro.2017.12.035}, pmid = {29408638}, issn = {1528-0012}, mesh = {Abdominal Pain/blood/diagnostic imaging/*etiology/therapy ; Aged ; Angioedema/blood/diagnostic imaging/*etiology ; Anti-Infective Agents/therapeutic use ; *B-Lymphocytes ; Clostridioides difficile/isolation &amp; purification ; Colonoscopy ; Diarrhea/blood/diagnostic imaging/*etiology/therapy ; Enterocolitis, Pseudomembranous/diagnostic imaging/microbiology/therapy ; Fecal Microbiota Transplantation ; Female ; Humans ; Intestine, Small/blood supply/diagnostic imaging/microbiology/pathology ; Irritable Bowel Syndrome/diagnostic imaging/microbiology/therapy ; Lymphocytosis/*complications/diagnosis ; Recurrence ; Tomography, X-Ray Computed ; }, }
@article {pmid29408609, year = {2018}, author = {Sun, X and Winglee, K and Gharaibeh, RZ and Gauthier, J and He, Z and Tripathi, P and Avram, D and Bruner, S and Fodor, A and Jobin, C}, title = {Microbiota-Derived Metabolic Factors Reduce Campylobacteriosis in Mice.}, journal = {Gastroenterology}, volume = {154}, number = {6}, pages = {1751-1763.e2}, pmid = {29408609}, issn = {1528-0012}, support = {R01 AI067846/AI/NIAID NIH HHS/United States ; R01 AT008623/AT/NCCIH NIH HHS/United States ; R01 DK047700/DK/NIDDK NIH HHS/United States ; R21 AI082319/AI/NIAID NIH HHS/United States ; }, mesh = {Anaerobiosis ; Animals ; Bile Acids and Salts/*administration &amp; dosage ; Campylobacter Infections/*microbiology ; Campylobacter jejuni/*metabolism ; Cholagogues and Choleretics/administration &amp; dosage ; Colon/microbiology ; Culture Techniques/methods ; Deoxycholic Acid/administration &amp; dosage ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastroenteritis/*microbiology ; Gastrointestinal Microbiome/*physiology ; Intestines/cytology ; Lithocholic Acid/administration &amp; dosage ; Mice ; Mice, Inbred C57BL ; Ursodeoxycholic Acid/administration &amp; dosage ; }, abstract = {BACKGROUND &amp; AIMS: Campylobacter jejuni, a prevalent foodborne bacterial pathogen, exploits the host innate response to induce colitis. Little is known about the roles of microbiota in C jejuni-induced intestinal inflammation. We investigated interactions between microbiota and intestinal cells during C jejuni infection of mice.<br><br>METHODS: Germ-free C57BL/6 Il10[-/-] mice were colonized with conventional microbiota and infected with a single dose of C jejuni (10[9] colony-forming units/mouse) via gavage. Conventional microbiota were cultured under aerobic, microaerobic, or anaerobic conditions and orally transplanted into germ-free Il10[-/-] mice. Colon tissues were collected from mice and analyzed by histology, real-time polymerase chain reaction, and immunoblotting. Fecal microbiota and bile acids were analyzed with 16S sequencing and high-performance liquid chromatography with mass spectrometry, respectively.<br><br>RESULTS: Introduction of conventional microbiota reduced C jejuni-induced colitis in previously germ-free Il10[-/-] mice, independent of fecal load of C jejuni, accompanied by reduced activation of mammalian target of rapamycin. Microbiota transplantation and 16S ribosomal DNA sequencing experiments showed that Clostridium XI, Bifidobacterium, and Lactobacillus were enriched in fecal samples from mice colonized with microbiota cultured in anaerobic conditions (which reduce colitis) compared with mice fed microbiota cultured under aerobic conditions (susceptible to colitis). Oral administration to mice of microbiota-derived secondary bile acid sodium deoxycholate, but not ursodeoxycholic acid or lithocholic acid, reduced C jejuni-induced colitis. Depletion of secondary bile acid-producing bacteria with antibiotics that kill anaerobic bacteria (clindamycin) promoted C&#xa0;jejuni-induced colitis in specific pathogen-free Il10[-/-] mice compared with the nonspecific antibiotic nalidixic acid; colitis induction by antibiotics was associated with reduced level of luminal deoxycholate.<br><br>CONCLUSIONS: We identified a mechanism by which the microbiota controls susceptibility to C jejuni infection in mice, via bacteria-derived secondary bile acids.}, }
@article {pmid29402478, year = {2018}, author = {Schoster, A}, title = {Probiotic Use in Equine Gastrointestinal Disease.}, journal = {The Veterinary clinics of North America. Equine practice}, volume = {34}, number = {1}, pages = {13-24}, doi = {10.1016/j.cveq.2017.11.004}, pmid = {29402478}, issn = {1558-4224}, mesh = {Animals ; Gastrointestinal Diseases/therapy/*veterinary ; Horse Diseases/*therapy ; Horses ; Probiotics/*therapeutic use ; }, abstract = {Probiotics are commonly used in human and veterinary medicine due to their postulated positive effects on overall and specifically gastrointestinal health. Although some beneficial effects have been shown in several human diseases, a general beneficial effect of probiotics is currently not supported. In horses, well-designed studies to date are few, results are conflicting, and the effects of probiotics are questionable. Adverse effects are rare; however, intestinal adverse effects (diarrhea) have been reported in foals. Quality control of over-the-counter probiotics is not tightly regulated, and labels often do not reflect the content.}, }
@article {pmid29397391, year = {2018}, author = {Winter, G and Hart, RA and Charlesworth, RPG and Sharpley, CF}, title = {Gut microbiome and depression: what we know and what we need to know.}, journal = {Reviews in the neurosciences}, volume = {29}, number = {6}, pages = {629-643}, doi = {10.1515/revneuro-2017-0072}, pmid = {29397391}, issn = {2191-0200}, mesh = {Animals ; Brain/metabolism/microbiology ; Depression/*metabolism/*microbiology/prevention &amp; control ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology/physiology ; Humans ; }, abstract = {Gut microbiome diversity has been strongly associated with mood-relating behaviours, including major depressive disorder (MDD). This association stems from the recently characterised bi-directional communication system between the gut and the brain, mediated by neuroimmune, neuroendocrine and sensory neural pathways. While the link between gut microbiome and depression is well supported by research, a major question needing to be addressed is the causality in the connection between the two, which will support the understanding of the role that the gut microbiota play in depression. In this article, we address this question by examining a theoretical 'chronology', reviewing the evidence supporting two possible sequences of events. First, we discuss that alterations in the gut microbiota populations of specific species might contribute to depression, and secondly, that depressive states might induce modification of specific gut microbiota species and eventually contribute to more severe depression. The feasibility of both sequences is supported by pre-clinical trials. For instance, research in rodents has shown an onset of depressive behaviour following faecal transplantations from patients with MDD. On the other hand, mental induction of stress and depressive behaviour in rodents resulted in reduced gut microbiota richness and diversity. Synthesis of these chronology dynamics raises important research directions to further understand the role that gut microbiota play in mood-relating behaviours, which holds substantial potential clinical outcomes for persons who experience MDD or related depressive disorders.}, }
@article {pmid29397331, year = {2018}, author = {Broglie, L and Rademaker, A and Galvin, J and Ray, A and Tse, WT and Duerst, R and Schneiderman, J and Kletzel, M and Chaudhury, S}, title = {Fecal calprotectin and serum albumin as markers of gastrointestinal graft versus host disease.}, journal = {Hematology/oncology and stem cell therapy}, volume = {11}, number = {3}, pages = {169-174}, doi = {10.1016/j.hemonc.2017.12.003}, pmid = {29397331}, issn = {2589-0646}, mesh = {Adolescent ; Adult ; Aged ; Allografts ; Biomarkers/metabolism ; Child ; Child, Preschool ; Fanconi Anemia/metabolism/therapy ; Feces ; Female ; Graft vs Host Disease/etiology/*metabolism ; Hematologic Neoplasms/metabolism/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Inflammatory Bowel Diseases/etiology/*metabolism ; Leukocyte L1 Antigen Complex/*metabolism ; Male ; Middle Aged ; Serum Albumin/*metabolism ; }, abstract = {BACKGROUND: Acute graft versus host disease (aGVHD) affects approximately 30-60% of patients after allogeneic hematopoietic stem cell transplantation (HCT) and our ability to predict who develops this complication and their response to treatment is limited. Fecal calprotectin has recently gained popularity as an effective marker of GI inflammation in patients with Inflammatory Bowel Disease (IBD).<br><br>METHODS: Fecal calprotectin and albumin were evaluated as prognostic and predictive markers of aGVHD in 60 adult and pediatric HCT patients. Stool samples were sent for calprotectin quantification prior to starting conditioning, at day 14 post-HCT, at day 28 post-HCT, and at onset of aGVHD &#xb1;&#x202f;2 days.<br><br>RESULTS: Fecal calprotectin did not differentiate patients with GI-GVHD and non-GI GVHD and did not vary based on severity. However, in patients with steroid-refractory GI aGVHD, significantly higher fecal calprotectin levels were noted. At onset of lower-GI symptoms, steroid refractory patients (n&#x202f;=&#x202f;3) had a mean fecal calprotectin level of 449&#x202f;ug/g (range 116-1111&#x202f;ug/g) and a mean albumin of 1.93&#x202f;g/dL (range 1.6-2.3&#x202f;g/dL) compared with a mean fecal calprotectin of 24&#x202f;ug/g (range 16-31&#x202f;ug/g) and a mean albumin of 3.3&#x202f;g/dL (range 2.3-3.9&#x202f;g/dL) in steroid responsive patients (n&#x202f;=&#x202f;9) (fecal calprotectin p&#x202f;=&#x202f;0.032, albumin p&#x202f;=&#x202f;0.027).<br><br>CONCLUSION: Patients with steroid-refractory GI aGVHD had higher fecal calprotectin levels and lower albumin levels than patients with steroid-responsive disease. We recommend further studies to evaluate non-invasive tests with fecal calprotectin in combination with albumin in predicting steroid refractory disease at onset of symptoms to potentially identify patients that may benefit from upfront escalation in GVHD treatment.}, }
@article {pmid29396112, year = {2018}, author = {Maignan, A and Ouaïssi, M and Turrini, O and Regenet, N and Loundou, A and Louis, G and Moutardier, V and Dahan, L and Pirrò, N and Sastre, B and Delpero, JR and Sielezneff, I}, title = {Risk factors of exocrine and endocrine pancreatic insufficiency after pancreatic resection: A multi-center prospective study.}, journal = {Journal of visceral surgery}, volume = {155}, number = {3}, pages = {173-181}, doi = {10.1016/j.jviscsurg.2017.10.007}, pmid = {29396112}, issn = {1878-7886}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Endocrine System Diseases/diagnosis/epidemiology/*etiology ; Exocrine Pancreatic Insufficiency/diagnosis/epidemiology/*etiology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; *Pancreatectomy ; *Pancreaticoduodenectomy ; Postoperative Complications/diagnosis/epidemiology/*etiology ; Prospective Studies ; Risk Factors ; Young Adult ; }, abstract = {UNLABELLED: Management of functional consequences after pancreatic resection has become a new therapeutic challenge. The goal of our study is to evaluate the risk factors for exocrine (ExoPI) and endocrine (EndoPI) pancreatic insufficiency after pancreatic surgery and to establish a predictive model for their onset.<br><br>PATIENTS AND METHODS: Between January 1, 2014 and June 19, 2015, 91 consecutive patients undergoing pancreatoduodenectomy (PD) or left pancreatectomy (LP) (72% and 28%, respectively) were followed prospectively. ExoPI was defined as fecal elastase content<200&#x3bc;g per gram of feces while EndoPI was defined as fasting glucose>126mg/dL or aggravation of preexisting diabetes. The volume of residual pancreas was measured according to the same principles as liver volumetry.<br><br>RESULTS: The ExoPI and EndoPI rates at 6 months were 75.9% and 30.8%, respectively. The rate of ExoPI after PD was statistically significantly higher than after LP (98% vs. 21%; P<0.001), while the rate of EndoPI was lower after PD vs. LP, but this difference did not reach statistical significance (28% vs. 38.5%; P=0.412). There was no statistically significant difference in ExoPI found between pancreatico-gastrostomy (PG) and pancreatico-jejunostomy (PJ) (100% vs. 98%; P=1.000). Remnant pancreatic volume less than 39.5% was predictive of ExoPI.<br><br>CONCLUSION: ExoPI occurs quasi-systematically after PD irrespective of the reconstruction scheme. The rate of EndoPI did not differ between PD and LP.}, }
@article {pmid29391359, year = {2018}, author = {Evans, TJ and Hilton, R and Douthwaite, S}, title = {Treating chronic hepatitis E: when is enough enough?.}, journal = {BMJ case reports}, volume = {2018}, number = {}, pages = {}, pmid = {29391359}, issn = {1757-790X}, mesh = {Adult ; Alanine Transaminase/metabolism ; Antiviral Agents/*therapeutic use ; Feces/*virology ; Hepatitis E/*drug therapy/immunology/physiopathology ; Hepatitis, Chronic/*drug therapy/immunology/physiopathology ; Humans ; Immunocompromised Host ; Kidney Transplantation ; Male ; Opportunistic Infections/*drug therapy/immunology/virology ; Ribavirin/*therapeutic use ; Treatment Outcome ; *Viral Load ; Virus Shedding ; }, abstract = {We present a 38-year-old white British man who was taking long-term immunosuppressive medication following kidney transplantation. On routine review, he was noted to have an isolated and asymptomatic rise in alanine aminotransferase. After thorough investigation, he was found to have positive IgM and IgG serology to hepatitis E virus-and given the duration of his transaminitis, he was determined to have chronic hepatitis E infection. Treatment options were complicated by the presence of his kidney transplant, by chronic anaemia and by his wish for concomitant fertility treatment. Ribavirin therapy was instituted with a dramatic and immediate drop in serum viral load, although stool viraemia persisted. No clear protocols guide duration of treatment in chronic hepatitis E infection, but protracted faecal virus shedding predicts viral recrudescence, and treatment should continue at least until the stool is clear of virus.}, }
@article {pmid30828578, year = {2018}, author = {Bakke, D and Chatterjee, I and Agrawal, A and Dai, Y and Sun, J}, title = {Regulation of Microbiota by Vitamin D Receptor: A Nuclear Weapon in Metabolic Diseases.}, journal = {Nuclear receptor research}, volume = {5}, number = {}, pages = {}, pmid = {30828578}, issn = {2314-5706}, support = {R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; }, abstract = {Metabolic syndrome is a multi-faceted disease. The microbiota, as a newly discovered organ, contributes to the pathogenesis and progression of metabolic syndrome. Recent studies have demonstrated that nuclear receptors play critical roles in metabolic diseases. In the current review, we discuss the general role of the microbiome in health and metabolic syndrome. We summarize the functions of the nuclear receptor vitamin D receptor (VDR) in metabolism. The focus of this review is the novel roles of vitamin D/VDR signaling in regulating inflammation and the microbiome, especially in obesity. Furthermore, we extend our discussion of potential gut-liver axis mediated by VDR signaling and microbiota in obesity. Finally, we discuss the potential clinical application of probiotics and fecal microbiota transplantation in prevention and treatment of metabolic syndrome. Insights into nuclear receptors in metabolism and metabolic diseases will allow us to develop new strategies for fighting metabolic diseases.}, }
@article {pmid30225401, year = {2017}, author = {Tariq, R and Weatherly, RM and Kammer, PP and Pardi, DS and Khanna, S}, title = {Experience and Outcomes at a Specialized Clostridium difficile Clinical Practice.}, journal = {Mayo Clinic proceedings. Innovations, quality &amp; outcomes}, volume = {1}, number = {1}, pages = {49-56}, pmid = {30225401}, issn = {2542-4548}, abstract = {OBJECTIVE: To report our experience with and outcomes among patients referred to a specialized Clostridium difficile clinical practice.<br><br>PATIENTS AND METHODS: We retrospectively identified consecutive patients referred for Clostridium difficile infection (CDI) management from January 1, 2013, through May 30, 2015. Data were collected for demographic characteristics, CDI history, final diagnoses, and management.<br><br>RESULTS: Overall, 211 patients (median age, 65 years; 66.4% women) were included. The most common indications for referral were recurrent CDI in 199 patients (94.3%), first CDI episode in 5 patients (2.4%), and chronic diarrhea in 7 patients (3.3%). After evaluation, the diagnoses were recurrent CDI in 127 patients (60.2%), resolved CDI in 36 patients (17.1%), first-episode CDI in 5 patients (2.4%), and non-CDI in 43 patients (20.4%). The most common non-CDI diagnoses were postinfection irritable bowel syndrome (PI-IBS) in 32 patients (15.2% overall), inflammatory bowel disease (n=3), small intestinal bacterial overgrowth (n=2), microscopic colitis (n=1), and asymptomatic C difficile colonization (n=2). Two patients had diabetic gastroparesis and food intolerances, and 1 had chronic constipation with overflow diarrhea. Of 127 patients with recurrent CDI, 30 (23.6%) received antibiotics; of these 30, 12 had antibiotic treatment failure and received fecal microbiota transplantation (FMT) for recurrent CDI. Among 97 patients (76.4%) who underwent FMT, 85 (87.6%) were cured after the first FMT, 5 were cured after the second FMT, and 7 were treated with antibiotics for FMT failure, with resolution of symptoms.<br><br>CONCLUSION: A substantial proportion of patients referred for CDI subsequently received alternative diagnoses; PI-IBS was the most common. Patients being referred for recurrent CDI should be evaluated carefully for alternative diagnoses.}, }
@article {pmid30063458, year = {2017}, author = {Fluitman, KS and De Clercq, NC and Keijser, BJF and Visser, M and Nieuwdorp, M and IJzerman, RG}, title = {The intestinal microbiota, energy balance, and malnutrition: emphasis on the role of short-chain fatty acids.}, journal = {Expert review of endocrinology &amp; metabolism}, volume = {12}, number = {3}, pages = {215-226}, doi = {10.1080/17446651.2017.1318060}, pmid = {30063458}, issn = {1744-8417}, abstract = {Malnutrition refers to both over- and undernutrition and results from a disruption in energy balance. It affects one in three people worldwide and is associated with increased morbidity and mortality. The intestinal microbiota represents a newly identified factor that might contribute to the development of malnutrition, as it harbors traits that complement the human metabolic and endocrine capabilities, thereby influencing energy balance. Areas covered: In the current review, we aim to give a comprehensive overview on the microbiota, its development and its possible influence on energy balance, with emphasis the role of short-chain fatty acids. We also consider microbial characteristics associated with obesity and undernutrition and evaluate microbial manipulating strategies. The PubMed database was searched using the terms: 'gastrointestinal microbiota', 'volatile fatty acids', 'malnutrition', 'undernutrition', 'obesity', 'insulin resistance', 'prebiotics', 'probiotics', 'antibiotics' and 'fecal microbiota transplantation'. Expert commentary: Microbiota make important contributions to the regulation of energy balance, whereas microbial disturbances might predispose to malnutrition. If we manage to manipulate the microbiota to our benefit, it could lead to preventive or therapeutic strategies targeting malnutrition.}, }
@article {pmid30566798, year = {2017}, author = {Mizuno, S and Kanai, T}, title = {Fecal microbiota transplantation.}, journal = {Nihon rinsho. Japanese journal of clinical medicine}, volume = {75}, number = {3}, pages = {492-497}, pmid = {30566798}, issn = {0047-1852}, mesh = {Colitis, Ulcerative/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Humans ; }, abstract = {Various strains of microorganisms inhabit the human intestinal tract, and disturbance of intestinal flora, dysbiosis, is thought to be pathogenesis of various diseases. Inducing symbiosis of intestinal flora has therapeutic potential for gastrointestinal diseases, but there are limited therapeutic options including probiotics.'Previous reports suggested that fecal microbiota transplantation (FMT) was a very useful choice in treatment for recurrent Clostridium difficile infection. FMT for ulcerative colitis (UC) patients is proposed as a potential treatment for resolving dysbiosis. There is some debate as to whether FMT for UC patients is effective or not. It remains a challenge for future research to make more sophisticated and convenient methods of FMT.}, }
@article {pmid29905273, year = {2017}, author = {Srinivasan, I and Tang, SJ and Sones, JQ}, title = {Fecal microbial transplantation.}, journal = {VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy}, volume = {2}, number = {4}, pages = {73}, doi = {10.1016/j.vgie.2017.01.008}, pmid = {29905273}, issn = {2468-4481}, }
@article {pmid30272930, year = {2017}, author = {Brodovskyi, SP and Iftodiy, AG and Kozlovska, IM}, title = {[ОPTIMIZATION OF SURGICAL TREATMENT OF HEMORRHOIDAL DISEASE STAGES III-IV].}, journal = {Klinichna khirurhiia}, volume = {}, number = {2}, pages = {10-12}, pmid = {30272930}, issn = {0023-2130}, mesh = {Abscess/diagnosis/pathology ; Adult ; Anal Canal/abnormalities/pathology ; Electrocoagulation/instrumentation/*methods ; Fecal Incontinence/diagnosis/pathology ; Female ; Hemorrhoidectomy/instrumentation/*methods ; Hemorrhoids/pathology/*surgery ; Humans ; Intraoperative Complications/diagnosis/pathology ; Laser Therapy/instrumentation/*methods ; Male ; Middle Aged ; Muscular Diseases/diagnosis/pathology ; Operative Blood Salvage/*methods ; Radiofrequency Therapy ; *Recovery of Function ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {The treatment results in patients, suffering chronic hemorrhoidal disease stages III- IV, in accordance to the elaborated method of hemorrhoidectomy, using radio-wave scalpel «Surgitron TM» with further welding of vascular pedicle, applying high-frequency electrocoagulator ЕК-301М1, are presented. In the patients, оperated on in accordance to the method proposed, the intraoperative complications rate and the blood loss severity were essentially lesser than in a comparison group. Owing an adequate level of surgical skills, the operative treatment method elaborated guarantees the reduction of early and late postoperative morbidity, rapid coming back to routine way of living postoperatively.}, }
@article {pmid29666652, year = {2017}, author = {Zhao, H and Shi, Y and Luo, X and Peng, L and Yang, Y and Zou, L}, title = {The Effect of Fecal Microbiota Transplantation on a Child with Tourette Syndrome.}, journal = {Case reports in medicine}, volume = {2017}, number = {}, pages = {6165239}, pmid = {29666652}, issn = {1687-9627}, abstract = {Tourette syndrome is a neuropsychiatric disorder with onset in childhood. New therapies are needed to effectively manage and treat this condition. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Here, we report a case in which fecal microbiota transplantation (FMT) is used to treat a child with Tourette syndrome, whose symptoms ameliorated dramatically in the following eight weeks.}, }
@article {pmid29979524, year = {2016}, author = {Verspohl, E}, title = {[In process].}, journal = {Medizinische Monatsschrift fur Pharmazeuten}, volume = {39}, number = {12}, pages = {539-542}, pmid = {29979524}, issn = {0342-9601}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Clostridium Infections/*therapy ; Diarrhea/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Probiotics/adverse effects/therapeutic use ; Treatment Outcome ; }, }
@article {pmid30044904, year = {2016}, author = {Preda, CM and Meianu, C and Sandra, I and Becheanu, G and Dumbrava, M and Manuc, M and Diculescu, M}, title = {Fecal Microbiota Transplantation in Recurrent NAP1/B1/027 Clostridium Difficile Infection (CDI) Resistant to Vancomycin and Metronidazole in a Patient with Ulcerative Colitis (UC): A Case Report.}, journal = {Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi}, volume = {120}, number = {3}, pages = {563-567}, pmid = {30044904}, issn = {0048-7848}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/drug effects ; Clostridium Infections/*drug therapy ; Colitis, Ulcerative/*complications ; Drug Resistance, Bacterial ; *Fecal Microbiota Transplantation ; Humans ; Male ; Metronidazole/therapeutic use ; Vancomycin/therapeutic use ; }, abstract = {Most of the studies showed that IBD patients inflammatory bowel diseases (IBD) with CDI have more of the whole range of short- and long-term worst outcomes than those without CDI. Initial infection with the BI/NAP1/027 epidemic clone was found to be a significant risk factor for relapse. However, current literature is suggesting increasingly that for patients with infections that fail to resolve with traditional antibiotic regimens, FMAT's average cure rate of >90%. We report a case of a 40-year-old man, diagnosed with ulcerative colitis (UC) in 2012 who presented in our clinic for 20 watery stools per day with mucus and blood, hypogastric pain, pyrexia and chills. Rectosigmoidoscopy and histopathological examination diagnosed a ctive lesions of ulcerative colitis with Clostridium difficile toxins A/B enzyme immunoassays (EIA) testing initially negative. The patient was non-responder at day 10 of intravenous (iv) corticotherapy and received induction therapy with Infliximab 5 mg/kg. EIA testing for Clostridium difficile was repeated at day 12 of hospitalization with positive results for toxins A/B, and associated oral therapy with Vancomycin and Metronidazole was initiated without clinical response in day 7, reasons for what intravenously therapy with Tigecycline was started with good response. Patient was discharged after 10 days of Tigecycline, but came back twice for two relapses of Clostridium difficile colitis treated successfully with Tigecycline, reasons for what fecal transplantation was performed in Matei Bals Institute, which induced remission of both CDI and UC.}, }
@article {pmid30050839, year = {2016}, author = {Chaitman, J and Jergens, AE and Gaschen, F and Garcia-Mazcorro, JF and Marks, SL and Marroquin-Cardona, AG and Richter, K and Rossi, G and Suchodolski, JS and Weese, JS}, title = {Commentary on key aspects of fecal microbiota transplantation in small animal practice.}, journal = {Veterinary medicine (Auckland, N.Z.)}, volume = {7}, number = {}, pages = {71-74}, pmid = {30050839}, issn = {2230-2034}, abstract = {The gastrointestinal tract of dogs, cats, and other mammals including humans harbors millions of beneficial microorganisms that regulate and maintain health. Fecal microbiota transplantation (FMT) is a procedure involving the administration of a fecal infusion from a healthy individual (donor) to a patient with disease to help improve health. Despite the effectiveness of FMT to treat intestinal disorders in humans, in particular recurrent Clostridium difficile infection, there is a paucity of scientific data regarding the application of FMT in veterinary patients. Here, we outline key aspects of FMT in small animal practice.}, }
@article {pmid31149088, year = {2016}, author = {Grigorescu, I and Dumitrascu, DL}, title = {IMPLICATION OF GUT MICROBIOTA IN DIABETES MELLITUS AND OBESITY.}, journal = {Acta endocrinologica (Bucharest, Romania : 2005)}, volume = {12}, number = {2}, pages = {206-214}, pmid = {31149088}, issn = {1841-0987}, abstract = {BACKGROUND AND AIMS: Differences in the composition of the species of microorganisms in the gut may predict the evolution toward obesity and diabetes mellitus. We carried out a systematic review of the studies dedicated to the role of gut microbiota in diabetes mellitus and obesity.<br><br>METHODS: A systematic literature search of electronic databases was performed, using the search syntax: "Gut microbiota and diabetes and obesity"; abstracts in English, with data about mechanisms of pathogenesis and treatment options by changing the gut composition were included (259 articles). Studies were excluded if they did not have an abstract, or they contained no data about the exact implication mechanism of microbiota.<br><br>RESULTS: There are differences regarding the composition of the gut microbiota in healthy people and type 2 diabetes mellitus patients; the later proved to have significantly decreased Clostridium components, and increased Lactobacillus and Bifidobacterium populations.The intestines of obese subjects are less rich in microbial genes, have a reduced amount of Bacteroidetes and an increased amount of Firmicutes. Fecal microbiota transplantation from obese subjects resulted in adoption of the donor somatotype. Early differences in gut microbiota composition (higher number of Bifidobacteria) function as diagnostic markers for the development of type 2 diabetes mellitus in high-risk patients.The gut endotoxins contribute to metabolic syndrome manifestation. Experimental studies with prebiotic showed lower levels of cytokines and antiobesity potential.<br><br>CONCLUSION: Microbiota composition and its changes since childhood have an important role in the metabolic syndrome. Any intervention in order to prevent or treat obesity and diabetes mellitus should have as target the gut immune system.}, }
@article {pmid29736438, year = {2015}, author = {Stuntz, M and des Vignes, F}, title = {Treating Clostridium difficile infections: Should fecal microbiota transplantation be reclassified from investigational drug to human tissue?.}, journal = {Contemporary clinical trials communications}, volume = {1}, number = {}, pages = {39-41}, pmid = {29736438}, issn = {2451-8654}, abstract = {Fecal microbiota transplantation (FMT) has emerged as a highly effective treatment for Clostridium difficile infection (CDI), the most frequent cause of hospital-acquired infectious diarrhea in developed countries and the cause of nearly 30,000 annual deaths in the US. FMT is proving to be more effective at treating CDI than traditional antibacterial therapy, and reduces the exposure of valuable antibiotics to potential resistance. A systematic review to assess the efficacy of FMT for CDI treatment showed that across all studies for recurrent CDI, symptom resolution was observed in 85% of patients. The United States Food and Drug Administration currently classifies FMT as an investigational drug, which imparts overly restrictive regulations that are impossible to apply to FMT in the same manner as conventional drugs. Reclassification of FMT to a human cell, tissue, and cellular and tissue-based product could potentially expand access to this important treatment while maintaining rigorous safety standards.}, }
@article {pmid30699613, year = {2014}, author = {Markakis, EA and Ligoxigakis, EK and Avramidou, EV and Tzanidakis, N}, title = {Survival, Persistence, and Infection Efficiency of Verticillium dahliae Passed Through the Digestive System of Sheep.}, journal = {Plant disease}, volume = {98}, number = {9}, pages = {1235-1240}, doi = {10.1094/PDIS-12-13-1201-RE}, pmid = {30699613}, issn = {0191-2917}, abstract = {The present study was carried out to determine the survival, persistence, and infection efficiency of Verticillium dahliae passed through the digestive tract of sheep. Eggplant, turnip, tomato, and pepper plants were artificially inoculated with 32 V. dahliae isolates. At 33 days postinoculation, the disease incidence and severity for eggplant, turnip, tomato, and pepper plants were 99.6, 96.2, 62.9, and 18.0% and 80.1, 49.8, 19.8, and 7.8%, respectively. The infected plant material was used to feed four 1-year-old sheep. Polymerase chain reaction assays revealed the presence of V. dahliae DNA in fecal samples received from animals' rectum on days 1, 2, 3, 4, and 5, whereas the pathogen DNA was not detected on 0, 6, and 7 days after feeding. Pathogenicity tests were conducted by transplanting eggplant plants into soil substrate amended with 20% decomposed manure, collected from the four animals fed with the infested forage. At 52 days after transplanting, manure-treated plants exhibited Verticillium wilt symptoms whereas, 2 months later, disease incidence, disease severity, and percentage of positive V. dahliae isolations from stem tissues were 58.3, 30.7, and 48.3%, respectively. Symptoms or positive isolations were not observed in control plants (transplanted in 100% soil substrate). This is the first report of the active role of V. dahliae passed through the digestive system of sheep as effective inoculum for host plants, in relation to the span persistence and transmission via the sheep carrier.}, }
@article {pmid29391279, year = {2018}, author = {Xiao, HW and Ge, C and Feng, GX and Li, Y and Luo, D and Dong, JL and Li, H and Wang, H and Cui, M and Fan, SJ}, title = {Gut microbiota modulates alcohol withdrawal-induced anxiety in mice.}, journal = {Toxicology letters}, volume = {287}, number = {}, pages = {23-30}, pmid = {29391279}, issn = {1879-3169}, support = {R01 AT005076/AT/NCCIH NIH HHS/United States ; R01 GM063075/GM/NIGMS NIH HHS/United States ; }, mesh = {Alcoholism/genetics/metabolism/*microbiology/psychology ; Animals ; Anxiety/genetics/metabolism/*microbiology/psychology ; Bacteria/classification/genetics/*growth &amp; development ; *Behavior, Animal ; Brain-Derived Neurotrophic Factor/genetics/metabolism ; Disease Models, Animal ; *Ethanol ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Hippocampus/metabolism ; Host-Pathogen Interactions ; Intestines/*microbiology ; Male ; Mice, Inbred C57BL ; Motor Activity ; Receptors, Corticotropin-Releasing Hormone/genetics/metabolism ; Receptors, Opioid, mu/genetics/metabolism ; Ribotyping ; Substance Withdrawal Syndrome/genetics/metabolism/*microbiology/psychology ; CRF Receptor, Type 1 ; }, abstract = {Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction.}, }
@article {pmid29388040, year = {2018}, author = {Huang, L and Zhu, Q and Qu, X and Qin, H}, title = {Microbial treatment in chronic constipation.}, journal = {Science China. Life sciences}, volume = {61}, number = {7}, pages = {744-752}, doi = {10.1007/s11427-017-9220-7}, pmid = {29388040}, issn = {1869-1889}, mesh = {Animals ; Chronic Disease/therapy ; Constipation/epidemiology/*therapy ; *Dietary Supplements ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology/physiopathology ; Humans ; Safety ; Treatment Outcome ; }, abstract = {Chronic functional constipation is a kind of common intestinal disease that occurs in children, adults and elderly people. This disease not only causes great influence to physiological function, but also results in varying degrees of psychological barriers. At present, constipation treatments continue to rely on traditional methods such as purgative therapy and surgery. However, these approaches can disrupt intestinal function. Recent research between intestinal diseases and gut microbiota has gradually revealed a connection between constipation and intestinal flora disturbance, providing a theoretical basis for microbial treatment in chronic constipation. Microbial treatment mainly includes probiotic preparations such as probiotics, prebiotics, synbiotics and fecal microbiota transplantation (FMT). Due to its safety, convenience and curative effect, probiotic preparations have been widely accepted, especially gradually developed FMT with higher curative effects. Microbial treatment improves clinical symptoms, promotes the recovery of intestinal flora, and has no complications during the treatment process. Compared with traditional treatments, microbial treatment in chronic constipation has advantages, and is worthy of further promotion from clinical research to clinical application.}, }
@article {pmid29385143, year = {2018}, author = {Mintz, M and Khair, S and Grewal, S and LaComb, JF and Park, J and Channer, B and Rajapakse, R and Bucobo, JC and Buscaglia, JM and Monzur, F and Chawla, A and Yang, J and Robertson, CE and Frank, DN and Li, E}, title = {Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0190997}, pmid = {29385143}, issn = {1932-6203}, support = {P30 DK048520/DK/NIDDK NIH HHS/United States ; }, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Colitis, Ulcerative/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Longitudinal Studies ; *Microbiota ; Polymerase Chain Reaction ; Prospective Studies ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only).<br><br>METHOD: V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group.<br><br>RESULTS: Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT.<br><br>CONCLUSION: The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.}, }
@article {pmid29383671, year = {2018}, author = {Bruxelle, JF and Péchiné, S and Collignon, A}, title = {Immunization Strategies Against Clostridium difficile.}, journal = {Advances in experimental medicine and biology}, volume = {1050}, number = {}, pages = {197-225}, doi = {10.1007/978-3-319-72799-8_12}, pmid = {29383671}, issn = {0065-2598}, mesh = {Animals ; Antibodies, Bacterial/immunology ; Bacterial Vaccines/immunology ; Clostridioides difficile/pathogenicity ; Clostridium Infections/*immunology ; Host-Pathogen Interactions/immunology ; Humans ; *Immunization ; }, abstract = {C. difficile infection (CDI) is an important healthcare- but also community-associated disease. CDI is considered a public health threat and an economic burden. A major problem is the high rate of recurrences. Besides classical antibiotic treatments, new therapeutic strategies are needed to prevent infection, to treat patients and prevent recurrences. If fecal transplantation has been recommended to treat recurrences, another key approach is to restore immunity against C. difficile and its virulence factors. Here, after a summary concerning the virulence factors, the host immune response against C. difficile and its role in the outcome of disease, we review the different approaches of passive immunotherapies and vaccines developed against CDI. Passive immunization strategies are designed in function of the target antigen, the antibody-based product and its administration route. Similarly, for active immunization strategies, vaccine antigens can target toxins or surface proteins and immunization can be performed by parenteral or mucosal routes. For passive immunization and vaccination as well, we first present immunization assays performed in animal models and second in humans and associated clinical trials. The different studies are presented according to the mode of administration either parenteral or mucosal and the target antigens, either toxins or colonization factors.}, }
@article {pmid29383670, year = {2018}, author = {Maida, M and Mcilroy, J and Ianiro, G and Cammarota, G}, title = {Faecal Microbiota Transplantation as Emerging Treatment in European Countries.}, journal = {Advances in experimental medicine and biology}, volume = {1050}, number = {}, pages = {177-195}, doi = {10.1007/978-3-319-72799-8_11}, pmid = {29383670}, issn = {0065-2598}, mesh = {Clinical Studies as Topic ; Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Europe ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/therapy ; }, abstract = {Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections in the world and is a leading cause of morbidity and mortality in hospitalized patients.Although several antibiotics effectively treat CDI, some individuals do not respond to these drugs and may be cured by transplanting stool from healthy donors. This procedure, termed Faecal Microbiota Transplantation (FMT), has demonstrated remarkable efficacy as a treatment for recurrent CDI.FMT has also been investigated in other diseases and disorders where perturbations to the gut microbiota have been theorized to play a causative role in pathogenesis and severity, such as inflammatory bowel disease (IBD). Although FMT is currently not recommended to cure IBD patients in clinical practice, several studies have recently been carried out with promising results. The aim of future research is therefore to standardize protocols and develop FMT as a therapeutic option for these patients.This review summarizes data on the use of FMT as a treatment for CDI and IBD, with special attention given to studies conducted in European countries.}, }
@article {pmid29383667, year = {2018}, author = {Fitzpatrick, F and Skally, M and Brady, M and Burns, K and Rooney, C and Wilcox, MH}, title = {European Practice for CDI Treatment.}, journal = {Advances in experimental medicine and biology}, volume = {1050}, number = {}, pages = {117-135}, doi = {10.1007/978-3-319-72799-8_8}, pmid = {29383667}, issn = {0065-2598}, mesh = {Anti-Infective Agents/pharmacology/therapeutic use ; Clostridioides difficile/drug effects ; Clostridium Infections/*drug therapy/prevention &amp; control ; Europe ; Humans ; Microbiota/drug effects ; *Practice Guidelines as Topic ; Surveys and Questionnaires ; }, abstract = {Clostridium difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used routinely for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases CDI treatment guidelines outline the treatment options for a variety of CDI clinical scenarios, including use of the more traditional anti-CDI therapies (e.g., metronidazole, vancomycin), the role of newer anti-CDI agents (e.g., fidaxomicin), indications for surgical intervention and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). A 2017 survey of 20 European countries found that while the majority (n = 14) have national CDI guidelines that provide a variety of recommendations for CDI treatment, only five have audited guideline implementation. A variety of restrictions are in place in 13 (65%) countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. Novel anti-CDI agents are being evaluated in Phase III trials; it is not yet clear what will be the roles of these agents. Prophylaxis is an optimum approach to reduce the impact of CDI especially in high-risk populations; monoclonal antibodies, antibiotic blocking approaches and multiple vaccines are currently in advanced clinical trials. The treatment of recurrent CDI is particularly troublesome, and several different live bio therapeutics are being developed, in addition to FMT.}, }
@article {pmid29382834, year = {2018}, author = {Li, B and Guo, K and Zeng, L and Zeng, B and Huo, R and Luo, Y and Wang, H and Dong, M and Zheng, P and Zhou, C and Chen, J and Liu, Y and Liu, Z and Fang, L and Wei, H and Xie, P}, title = {Metabolite identification in fecal microbiota transplantation mouse livers and combined proteomics with chronic unpredictive mild stress mouse livers.}, journal = {Translational psychiatry}, volume = {8}, number = {1}, pages = {34}, pmid = {29382834}, issn = {2158-3188}, mesh = {Animals ; Behavior, Animal/physiology ; Depressive Disorder, Major/*metabolism/*microbiology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Gas Chromatography-Mass Spectrometry ; *Gastrointestinal Microbiome ; Humans ; Liver/*metabolism ; Magnetic Resonance Spectroscopy ; Metabolomics ; Mice ; Proteomics ; Stress, Psychological/*metabolism ; }, abstract = {Major depressive disorder (MDD) is a common mood disorder. Gut microbiota may be involved in the pathogenesis of depression via the microbe-gut-brain axis. Liver is vulnerable to exposure of bacterial products translocated from the gut via the portal vein and may be involved in the axis. In this study, germ-free mice underwent fecal microbiota transplantation from MDD patients and healthy controls. Behavioral tests verified the depression model. Metabolomics using gas chromatography-mass spectrometry, nuclear magnetic resonance, and liquid chromatography-mass spectrometry determined the influence of microbes on liver metabolism. With multivariate statistical analysis, 191 metabolites were distinguishable in MDD mice from control (CON) mice. Compared with CON mice, MDD mice showed lower levels for 106 metabolites and higher levels for 85 metabolites. These metabolites are associated with lipid and energy metabolism and oxidative stress. Combined analyses of significantly changed proteins in livers from another depression model induced by chronic unpredictive mild stress returned a high score for the Lipid Metabolism, Free Radical Scavenging, and Molecule Transports network, and canonical pathways were involved in energy metabolism and tryptophan degradation. The two mouse models of depression suggest that changes in liver metabolism might be involved in the pathogenesis of MDD. Conjoint analyses of fecal, serum, liver, and hippocampal metabolites from fecal microbiota transplantation mice suggested that aminoacyl-tRNA biosynthesis significantly changed and fecal metabolites showed a close relationship with the liver. These findings may help determine the biological mechanisms of depression and provide evidence about "depression microbes" impacting on liver metabolism.}, }
@article {pmid29382125, year = {2018}, author = {Nishimura, N and Tanabe, H and Komori, E and Sasaki, Y and Inoue, R and Yamamoto, T}, title = {Transplantation of High Hydrogen-Producing Microbiota Leads to Generation of Large Amounts of Colonic Hydrogen in Recipient Rats Fed High Amylose Maize Starch.}, journal = {Nutrients}, volume = {10}, number = {2}, pages = {}, pmid = {29382125}, issn = {2072-6643}, mesh = {Amylose/*administration &amp; dosage ; Animals ; Bacteroidetes ; Bifidobacterium ; Colon/metabolism/*microbiology ; Diet, High-Fat ; *Fecal Microbiota Transplantation ; Firmicutes ; *Gastrointestinal Microbiome ; Hydrogen/*metabolism ; RNA, Ribosomal, 16S/isolation &amp; purification ; Rats ; Ruminococcus ; Sequence Analysis, DNA ; Starch/*administration &amp; dosage ; Zea mays/chemistry ; }, abstract = {The hydrogen molecule (H2), which has low redox potential, is produced by colonic fermentation. We examined whether increased hydrogen (H2) concentration in the portal vein in rats fed high amylose maize starch (HAS) helped alleviate oxidative stress, and whether the transplantation of rat colonic microbiota with high H2 production can shift low H2-generating rats (LG) to high H2-generating rats (HG). Rats were fed a 20% HAS diet for 10 days and 13 days in experiments 1 and 2, respectively. After 10 days (experiment 1), rats underwent a hepatic ischemia-reperfusion (IR) operation. Rats were then categorized into quintiles of portal H2 concentration. Plasma alanine aminotransferase activity and hepatic oxidized glutathione concentration were significantly lower as portal H2 concentration increased. In experiment 2, microbiota derived from HG (the transplantation group) or saline (the control group) were orally inoculated into LG on days 3 and 4. On day 13, portal H2 concentration in the transplantation group was significantly higher compared with the control group, and positively correlated with genera Bifidobacterium, Allobaculum, and Parabacteroides, and negatively correlated with genera Bacteroides, Ruminococcus, and Escherichia. In conclusion, the transplantation of microbiota derived from HG leads to stable, high H2 production in LG, with the resultant high production of H2 contributing to the alleviation of oxidative stress.}, }
@article {pmid29380645, year = {2018}, author = {Libbey, JE and Sanchez, JM and Doty, DJ and Sim, JT and Cusick, MF and Cox, JE and Fischer, KF and Round, JL and Fujinami, RS}, title = {Variations in diet cause alterations in microbiota and metabolites that follow changes in disease severity in a multiple sclerosis model.}, journal = {Beneficial microbes}, volume = {9}, number = {3}, pages = {495-513}, pmid = {29380645}, issn = {1876-2891}, support = {R01 NS082102/NS/NINDS NIH HHS/United States ; S10 RR020883/RR/NCRR NIH HHS/United States ; T32 AI055434/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Body Weight ; Citric Acid Cycle ; Diet Therapy/*methods ; Disease Models, Animal ; Feces/chemistry/microbiology ; *Gastrointestinal Microbiome ; Glycolysis ; Lacticaseibacillus paracasei/isolation &amp; purification ; *Metabolome ; Mice ; Multiple Sclerosis/*pathology/*therapy ; Serum/chemistry ; *Severity of Illness Index ; }, abstract = {Multiple sclerosis (MS) is a metabolically demanding disease involving immune-mediated destruction of myelin in the central nervous system. We previously demonstrated a significant alteration in disease course in the experimental autoimmune encephalomyelitis (EAE) preclinical model of MS due to diet. Based on the established crosstalk between metabolism and gut microbiota, we took an unbiased sampling of microbiota, in the stool, and metabolites, in the serum and stool, from mice (Mus musculus) on the two different diets, the Teklad global soy protein-free extruded rodent diet (irradiated diet) and the Teklad sterilisable rodent diet (autoclaved diet). Within the microbiota, the genus Lactobacillus was found to be inversely correlated with EAE severity. Therapeutic treatment with Lactobacillus paracasei resulted in a significant reduction in the incidence of disease, clinical scores and the amount of weight loss in EAE mice. Within the metabolites, we identified shifts in glycolysis and the tricarboxylic acid cycle that may explain the differences in disease severity between the different diets in EAE. This work begins to elucidate the relationship between diet, microbiota and metabolism in the EAE preclinical model of MS and identifies targets for further study with the goal to more specifically probe the complex metabolic interaction at play in EAE that may have translational relevance to MS patients.}, }
@article {pmid29379189, year = {2018}, author = {Kroemer, G and Zitvogel, L}, title = {Cancer immunotherapy in 2017: The breakthrough of the microbiota.}, journal = {Nature reviews. Immunology}, volume = {18}, number = {2}, pages = {87-88}, pmid = {29379189}, issn = {1474-1741}, mesh = {Animals ; Biomarkers, Tumor/immunology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunotherapy/methods/*trends ; Mice ; Models, Immunological ; Neoplasms/*immunology/microbiology/*therapy ; Prognosis ; }, }
@article {pmid29375527, year = {2017}, author = {Hu, L and Geng, S and Li, Y and Cheng, S and Fu, X and Yue, X and Han, X}, title = {Exogenous Fecal Microbiota Transplantation from Local Adult Pigs to Crossbred Newborn Piglets.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {2663}, pmid = {29375527}, issn = {1664-302X}, abstract = {This study was conducted to investigate the effect of exogenous fecal microbiota transplantation on gut bacterial community structure, gut barrier and growth performance in recipient piglets. Twelve litters of Duroc × Landrace × Yorkshire piglets of the same birth and parity were weighed and divided into two groups. One group (recipient piglets) was inoculated orally with fecal microbiota suspension of healthy adult Jinhua pigs daily from day 1 to day 11. The other (control) was given orally the same volume of sterile physiological saline at the same time. The experiment lasted 27 days. The results showed that the relative abundance of Firmicutes, Prevotellaceae, Lachnospiraceae, Ruminococcus, Prevotella, and Oscillospira in the colon of recipient piglets was increased. Proteobacteria, Fusobacteriaceae, Clostridiaceae, Pasteuriaceae, Alcaligenaceae, Bacteroidaceae, Veillonellaceae, Sutterella, Escherichia, and Bacteroides in the colon of recipient piglets were decreased. An average daily weight gain of recipient piglets was increased, and diarrhea incidence of the recipient was decreased during the trial. Intestinal morphology and tight junction barrier of recipient piglets were improved. The optical density of sIgA[+] cells, the number of goblet cells and relative expressions of MUC2 in the intestinal mucosa of recipient piglets were enhanced. Protein expressions of β-defensin 2 and mRNA expressions of TLR2 and TLR4 in the intestinal mucosa of recipient piglets were also increased. These findings supported that the exogenous fecal microbiota had significant effects on animal's growth performance, intestinal barrier function, and innate immune via modulating the composition of the gut microbiota.}, }
@article {pmid29367525, year = {2017}, author = {Tanemoto, S and Sujino, T and Kanai, T}, title = {[Intestinal immune response is regulated by gut microbe].}, journal = {Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology}, volume = {40}, number = {6}, pages = {408-415}, doi = {10.2177/jsci.40.408}, pmid = {29367525}, issn = {1349-7413}, mesh = {Dysbiosis/immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology/*physiology ; Homeostasis/immunology ; Humans ; Inflammatory Bowel Diseases/immunology/microbiology/therapy ; Intestines/*immunology/*microbiology ; Symbiosis ; }, abstract = {Human Intestine has a diverse population of bacteria which induces pathogens to disrupt not only the intestinal homeostasis but whole body immune systems. Dysbiosis, the abnormal proliferation and reduction of the microbiota, breaks down the homeostasis of the immunity and metabolisms in the host. The evolution of the microbiota analysis technology contributed to reveal the molecular biological complex interaction between the microbiota and its host systemically as well as locally. Because several diseases are caused by the dysbiosis, fecal transplantation would be the new therapeutic target for them. It has been investigated in some intestinal diseases such as CD infection, or inflammatory bowel disease. Here, we review these symbiotic interactions and the current state for the clinical application.}, }
@article {pmid29366434, year = {2018}, author = {Barker, AK and Krasity, B and Musuuza, J and Safdar, N}, title = {Screening for Asymptomatic Clostridium difficile Among Bone Marrow Transplant Patients: A Mixed-Methods Study of Intervention Effectiveness and Feasibility.}, journal = {Infection control and hospital epidemiology}, volume = {39}, number = {2}, pages = {177-185}, pmid = {29366434}, issn = {1559-6834}, support = {T32 GM008692/GM/NIGMS NIH HHS/United States ; TL1 TR000429/TR/NCATS NIH HHS/United States ; UL1 TR000427/TR/NCATS NIH HHS/United States ; }, mesh = {Attitude of Health Personnel ; Bone Marrow Transplantation ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/*microbiology/mortality/*prevention &amp; control ; Cross Infection/*diagnosis/microbiology/mortality/*prevention &amp; control ; Feces/microbiology ; Humans ; Infection Control/*methods ; Interviews as Topic ; Length of Stay ; Polymerase Chain Reaction ; Regression Analysis ; Tertiary Care Centers ; Wisconsin/epidemiology ; }, abstract = {OBJECTIVE To identify facilitators and barriers to implementation of a Clostridium difficile screening intervention among bone marrow transplant (BMT) patients and to evaluate the clinical effectiveness of the intervention on the rate of hospital-onset C. difficile infection (HO-CDI). DESIGN Before-and-after trial SETTING A 505-bed tertiary-care medical center PARTICIPANTS All 5,357 patients admitted to the BMT and general medicine wards from January 2014 to February 2017 were included in the study. Interview participants included 3 physicians, 4 nurses, and 4 administrators. INTERVENTION All BMT patients were screened within 48 hours of admission. Colonized patients, as defined by a C. difficile-positive polymerase chain reaction (PCR) stool result, were placed under contact precautions for the duration of their hospital stay. METHODS Interview responses were coded according to the Systems Engineering Initiative for Patient Safety conceptual framework. We compared pre- and postintervention HO-CDI rates on BMT and general internal medicine units using time-series analysis. RESULTS Stakeholder engagement, at both the person and organizational level, facilitates standardization and optimization of intervention protocols. While the screening intervention was generally well received, tools and technology were sources of concern. The mean incidence of HO-CDI decreased on the BMT service postintervention (P<.0001). However, the effect of the change in the trend postintervention was not significantly different on BMT compared to the control wards (P=.93). CONCLUSIONS We report the first mixed-methods study to evaluate a C. difficile screening intervention among the BMT population. The positive nature by which the intervention was received by front-line clinical staff, laboratory staff, and administrators is promising for future implementation studies. Infect Control Hosp Epidemiol 2018;39:177-185.}, }
@article {pmid29363436, year = {2018}, author = {Jamot, S and Raghunathan, V and Patel, K and Kelly, CR and Lim, SH}, title = {Factors Associated with the Use of Fecal Microbiota Transplant in Patients with Recurrent Clostridium difficile Infections.}, journal = {Infection control and hospital epidemiology}, volume = {39}, number = {3}, pages = {302-306}, doi = {10.1017/ice.2017.314}, pmid = {29363436}, issn = {1559-6834}, mesh = {Academic Medical Centers ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; Clostridium Infections/*epidemiology/*therapy ; Cohort Studies ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Regression, Psychology ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; United States/epidemiology ; Vancomycin/therapeutic use ; Young Adult ; }, abstract = {OBJECTIVE To identify the factors associated with first Clostridium difficile infection (CDI) that predict fecal microbiota transplantation (FMT) for recurrent CDI DESIGN We carried out a retrospective single-center cohort study to compare the clinical characteristics of 200 patients who underwent FMT for recurrent CDI to 75 patients who did not. SETTING A single academic hospital in the United States PATIENTS Adult patients RESULTS The time from first to second CDI correlated to subsequent FMT use. Concomitant inflammatory bowel disease (IBD; P=.002), use of immunosuppressive therapy (P=.04), and use of metronidazole within 2 months before the first CDI (P=.02) correlated positively to subsequent FMT in univariate analysis. The use of oral vancomycin for first CDI was more common in those who required FMT than those who did not in univariate (P=.02) and multivariate (P=.03) analyses. In contrast, intravenous vancomycin use within 2 months before the first CDI reduced the risk for FMT in univariate P=.000003) and multivariate (P=.0001) analyses. Black patients with recurrent CDI were less likely to receive FMT than white patients (P=.00005). Patients who received FMT were also less likely to have comorbidities. CONCLUSIONS This study provides important insights into the factors predictive for FMT in patients with recurrent CDI and highlights the potential racial and medical characteristics that affect the access of the patients to FMT. Infect Control Hosp Epidemiol 2018;39:302-306.}, }
@article {pmid29361092, year = {2018}, author = {Goyal, A and Yeh, A and Bush, BR and Firek, BA and Siebold, LM and Rogers, MB and Kufen, AD and Morowitz, MJ}, title = {Safety, Clinical Response, and Microbiome Findings Following Fecal Microbiota Transplant in Children With Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {24}, number = {2}, pages = {410-421}, doi = {10.1093/ibd/izx035}, pmid = {29361092}, issn = {1536-4844}, mesh = {Adolescent ; Bacteria/classification ; Biomarkers/*analysis ; Child ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Inflammatory Bowel Diseases/*therapy ; Male ; Prospective Studies ; Remission Induction ; Severity of Illness Index ; }, abstract = {BACKGROUND: The role of fecal microbiota transplant (FMT) in the treatment of pediatric inflammatory bowel disease (IBD) is unknown. The aims of this study were to assess safety, clinical response, and gut microbiome alterations in children with Crohn's disease (CD), ulcerative colitis (UC), or indeterminate colitis (IC).<br><br>METHODS: In this open-label, single-center prospective trial, patients with IBD refractory to medical therapy underwent a single FMT by upper and lower endoscopy. Adverse events, clinical response, gut microbiome, and biomarkers were assessed at baseline, 1 week, 1 month, and 6 months following FMT.<br><br>RESULTS: Twenty-one subjects were analyzed, with a median age of 12 years, of whom 57% and 28% demonstrated clinical response at 1 and 6 months post-FMT, respectively. Two CD patients were in remission at 6 months. Adverse events attributable to FMT were mild to moderate and self-limited. Patients prior to FMT showed decreased species diversity and significant microbiome compositional differences characterized by increased Enterobacteriaceae, Enterococcus, Haemophilus, and Fusobacterium compared with donors and demonstrated increased species diversity at 30 days post-FMT. At 6 months, these changes shifted toward baseline. Clinical responders had a higher relative abundance of Fusobacterium and a lower diversity at baseline, as well as a greater shift toward donor-like microbiome after FMT compared with nonresponders.<br><br>CONCLUSIONS: A single FMT is relatively safe and can result in a short-term response in young patients with active IBD. Responders possessed increased Fusobacterium prior to FMT and demonstrated more significant microbiome changes compared with nonresponders after FMT. Microbiome characteristics may help in predicting response.}, }
@article {pmid29358877, year = {2018}, author = {Shen, ZH and Zhu, CX and Quan, YS and Yang, ZY and Wu, S and Luo, WW and Tan, B and Wang, XY}, title = {Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation.}, journal = {World journal of gastroenterology}, volume = {24}, number = {1}, pages = {5-14}, pmid = {29358877}, issn = {2219-2840}, mesh = {Animals ; Bacteria/*growth &amp; development/immunology ; Colitis, Ulcerative/diagnosis/immunology/microbiology/*therapy ; Colon/immunology/*microbiology ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Probiotics/adverse effects/*therapeutic use ; Treatment Outcome ; }, abstract = {Ulcerative colitis (UC) is an inflammatory disease that mainly affects the colon and rectum. It is believed that genetic factors, host immune system disorders, intestinal microbiota dysbiosis, and environmental factors contribute to the pathogenesis of UC. However, studies on the role of intestinal microbiota in the pathogenesis of UC have been inconclusive. Studies have shown that probiotics improve intestinal mucosa barrier function and immune system function and promote secretion of anti-inflammatory factors, thereby inhibiting the growth of harmful bacteria in the intestine. Fecal microbiota transplantation (FMT) can reduce bowel permeability and thus the severity of disease by increasing the production of short-chain fatty acids, especially butyrate, which help maintain the integrity of the epithelial barrier. FMT can also restore immune dysbiosis by inhibiting Th1 differentiation, activity of T cells, leukocyte adhesion, and production of inflammatory factors. Probiotics and FMT are being increasingly used to treat UC, but their use is controversial because of uncertain efficacy. Here, we briefly review the role of intestinal microbiota in the pathogenesis and treatment of UC.}, }
@article {pmid29358865, year = {2017}, author = {Liu, SX and Li, YH and Dai, WK and Li, XS and Qiu, CZ and Ruan, ML and Zou, B and Dong, C and Liu, YH and He, JY and Huang, ZH and Shu, SN}, title = {Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment.}, journal = {World journal of gastroenterology}, volume = {23}, number = {48}, pages = {8570-8581}, pmid = {29358865}, issn = {2219-2840}, mesh = {Colitis/immunology/microbiology/*therapy ; Diarrhea/immunology/microbiology/therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage/immunology/microbiology/therapy ; Gastrointestinal Microbiome/*immunology ; Humans ; Infant ; Male ; Recurrence ; Treatment Outcome ; }, abstract = {AIM: To investigate the impact of fecal microbiota transplantation (FMT) treatment on allergic colitis (AC) and gut microbiota (GM).<br><br>METHODS: We selected a total of 19 AC infants, who suffered from severe diarrhea/hematochezia, did not relieve completely after routine therapy or cannot adhere to the therapy, and were free from organ congenital malformations and other contraindications for FMT. Qualified donor-derived stools were collected and injected to the AC infants via a rectal tube. Clinical outcomes and follow-up observations were noted. Stools were collected from ten AC infants before and after FMT, and GM composition was assessed for infants and donors using 16S rDNA sequencing analysis.<br><br>RESULTS: After FMT treatment, AC symptoms in 17 infants were relieved within 2 d, and no relapse was observed in the next 15 mo. Clinical improvement was also detected in the other two AC infants who were lost to follow-up. During follow-up, one AC infant suffered from mild eczema and recovered shortly after hormone therapy. Based on the 16S rDNA analysis in ten AC infants, most of them (n = 6) had greater GM diversity after FMT. As a result, Proteobacteria decreased (n = 6) and Firmicutes increased (n = 10) in post-FMT AC infants. Moreover, Firmicutes accounted for the greatest proportion of GM in the patients. At the genus level, Bacteroides (n = 6), Escherichia (n = 8), and Lactobacillus (n = 4) were enriched in some AC infants after FMT treatment, but the relative abundances of Clostridium (n = 5), Veillonella (n = 7), Streptococcus (n = 6), and Klebsiella (n = 8) decreased dramatically.<br><br>CONCLUSION: FMT is a safe and effective method for treating pediatric patients with AC and restoring GM balance.}, }
@article {pmid29358788, year = {2018}, author = {Radovanovic-Dinic, B and Tesic-Rajkovic, S and Grgov, S and Petrovic, G and Zivkovic, V}, title = {Irritable bowel syndrome - from etiopathogenesis to therapy.}, journal = {Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia}, volume = {162}, number = {1}, pages = {1-9}, doi = {10.5507/bp.2017.057}, pmid = {29358788}, issn = {1804-7521}, mesh = {Diet ; Exercise ; Fecal Microbiota Transplantation ; *Genetic Predisposition to Disease ; Humans ; Irritable Bowel Syndrome/*diagnosis/etiology/physiopathology/therapy ; Laxatives ; Parasympatholytics ; Patient Education as Topic ; Practice Guidelines as Topic ; Prevalence ; Probiotics ; Quality of Life ; Risk Factors ; *Risk Reduction Behavior ; Stress, Psychological/*complications ; }, abstract = {Irritable bowel syndrome (IBS) is a chronic and relapsing functional gastrointestinal disorder that affects 9-23% of the population across the world. Patients with IBS are often referred to gastroenterology, undergo various investigations, take various medicines, take time off work and have a poor quality of life. The pathophysiology of IBS is not yet completely understood and seems to be multifactorial. Many pathogenetic factors, in various combinations, and not all necessarily present in each patient, can play an important role. Discomfort or abdominal pain relieived by defacation, asociated with a change in stool form, is a typical clinical manifestation of IBS. Many factors, such as emotional stress and eating, may exacerbate the symptoms. A timely diagnosis of IBS is important so that treatment which will provide adequate symptomatic relief (diarrhoea, constipation, pain and boaring) can be introduced. The diagnosis of IBS is not confirmed by a specific test or structural abnormality. It is made using criteria based on clinical symptoms such as Rome criteria, unless the symptoms are thought to be atypical. Today the Rome Criteria IV is the current gold-standard for the diagnoses of IBS. Treatment of patients with IBS requires a multidisciplinary approach. Some patients respond well to non-pharmacological treatment, while others also require pharmacological treatment. This review will provide a summary of pathophysiology, diagnostic criteria and therapies for IBS.}, }
@article {pmid29355542, year = {2018}, author = {Joshi, T and Elderd, BD and Abbott, KC}, title = {No appendix necessary: Fecal transplants and antibiotics can resolve Clostridium difficile infection.}, journal = {Journal of theoretical biology}, volume = {442}, number = {}, pages = {139-148}, doi = {10.1016/j.jtbi.2018.01.013}, pmid = {29355542}, issn = {1095-8541}, mesh = {Algorithms ; Animals ; Anti-Bacterial Agents/*administration &amp; dosage ; Appendix/microbiology ; Bacteria/immunology ; Clostridium/*drug effects/physiology ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/immunology/physiology ; Host-Pathogen Interactions/drug effects ; Humans ; Models, Biological ; }, abstract = {The appendix has been hypothesized to protect the colon against Clostridium difficile infection (CDI) by providing a continuous source of commensal bacteria that crowd out the potentially unhealthy bacteria and/or by contributing to defensive immune dynamics. Here, a series of deterministic systems comprised of ordinary differential equations, which treat the system as an ecological community of microorganisms, model the dynamics of colon microbiome. The first model includes migration of commensal bacteria from the appendix to the gut, while the second model expands this to also include immune dynamics. Simulations and simple analytic techniques are used to explore dynamics under biologically relevant parameters values. Both models exhibited bistability with steady states of a healthy state and of fulminant CDI. However, we find that the appendix size was much too small for migration to affect the stability of the system. Both models affirm the use of fecal transplants in conjunction with antibiotic use for CDI treatment, while the second model also suggests that anti-inflammatory drugs may protect against CDI. Ultimately, in general neither the appendiceal migration rate of commensal microbiota nor the boost to antibody production could exert an appreciable impact on the stability of the system, thus failing to support the proposed protective role of the appendix against CDI.}, }
@article {pmid29343312, year = {2018}, author = {Gopalsamy, SN and Sherman, A and Woodworth, MH and Lutgring, JD and Kraft, CS}, title = {Fecal Microbiota Transplant for Multidrug-Resistant Organism Decolonization Administered During Septic Shock.}, journal = {Infection control and hospital epidemiology}, volume = {39}, number = {4}, pages = {490-492}, pmid = {29343312}, issn = {1559-6834}, support = {UL1 TR002378/TR/NCATS NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; }, mesh = {*Anti-Bacterial Agents/administration &amp; dosage/adverse effects/classification ; Brain Injuries, Traumatic/surgery ; Craniotomy/adverse effects ; *Drug Resistance, Multiple, Bacterial ; Fatal Outcome ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/drug effects/physiology ; *Healthcare-Associated Pneumonia/microbiology/physiopathology/therapy ; Humans ; *Klebsiella Infections/diagnosis/drug therapy/etiology ; *Klebsiella pneumoniae/isolation &amp; purification/pathogenicity ; Male ; Middle Aged ; *Postoperative Complications/microbiology/physiopathology/therapy ; Respiration, Artificial/methods ; Time-to-Treatment ; }, }
@article {pmid29339099, year = {2018}, author = {Kosulin, K and Berkowitsch, B and Matthes, S and Pichler, H and Lawitschka, A and Pötschger, U and Fritsch, G and Lion, T}, title = {Intestinal Adenovirus Shedding Before Allogeneic Stem Cell Transplantation Is a Risk Factor for Invasive Infection Post-transplant.}, journal = {EBioMedicine}, volume = {28}, number = {}, pages = {114-119}, pmid = {29339099}, issn = {2352-3964}, mesh = {Adenoviruses, Human/*physiology ; Communicable Diseases/*virology ; Feces/virology ; Humans ; Incidence ; Intestines/*virology ; Kinetics ; Multivariate Analysis ; Risk Factors ; Species Specificity ; Stem Cell Transplantation/*adverse effects ; Time Factors ; Transplantation, Homologous ; Viremia/epidemiology ; *Virus Shedding ; }, abstract = {Human adenoviruses (HAdV) are a major cause of morbidity and mortality in pediatric human stem cell transplant (HSCT) recipients. Our previous studies identified the gastrointestinal tract as a site of HAdV persistence, but the role of intestinal virus shedding pre-transplant for the risk of ensuing invasive infection has not been entirely elucidated. Molecular HAdV monitoring of serial stool samples using RQ-PCR was performed in 304 children undergoing allogeneic HSCT. Analysis of stool and peripheral blood specimens was performed pre-transplant and at short intervals until day 100 post-HSCT. The virus was detected in the stool of 129 patients (42%), and 42 tested positive already before HSCT. The patients displaying HAdV shedding pre-transplant showed a significantly earlier increase of intestinal HAdV levels above the critical threshold associated with high risk of invasive infection (p<0.01). In this subset of patients, the occurrence of invasive infection characterized by viremia was significantly higher than in patients without HAdV shedding before HSCT (33% vs 7%; p<0.0001). The data demonstrate that intestinal HAdV shedding before HSCT confers a greatly increased risk for invasive infection and disseminated disease post-transplant, and highlights the need for timely HAdV monitoring and pre-emptive therapeutic considerations in HSCT recipients.}, }
@article {pmid29336930, year = {2018}, author = {Galpérine, T and Guery, B and , }, title = {Exploring ways to improve CDI outcomes.}, journal = {Medecine et maladies infectieuses}, volume = {48}, number = {1}, pages = {10-17}, doi = {10.1016/j.medmal.2017.10.009}, pmid = {29336930}, issn = {1769-6690}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Vaccines ; Clostridioides difficile/drug effects ; Clostridium Infections/drug therapy/microbiology/prevention &amp; control/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Immunization, Passive ; Recurrence ; Therapies, Investigational ; Treatment Outcome ; Vaccines, Synthetic ; }, abstract = {Clostridium difficile is an anaerobic spore-forming Gram-positive bacillus recognized as an evolving international health problem. Metronidazole and vancomycin were - until recently - the only drugs available to treat C. difficile infection (CDI). Better knowledge of the pathophysiology and the development of new drugs completely modified the management of initial episodes and recurrences of CDI. Fidaxomicin significantly reduced recurrences compared with vancomycin. New drugs are also currently evaluated (cadazolid, surotomycin, ridinilazole, rifaximin). Gut microbiota homeostasis was clearly shown to be a key determinant in recurrences as demonstrated by the development of gut microbiota transplantation and alternative microbiota substitution. Passive immunotherapy and vaccinal approaches are also currently being evaluated. In conclusion, CDI treatment has evolved with the development of new therapeutic pathways which now need to be implemented in international guidelines.}, }
@article {pmid29336929, year = {2018}, author = {Heimann, SM and Cruz Aguilar, MR and Mellinghof, S and Vehreschild, MJGT}, title = {Economic burden and cost-effective management of Clostridium difficile infections.}, journal = {Medecine et maladies infectieuses}, volume = {48}, number = {1}, pages = {23-29}, doi = {10.1016/j.medmal.2017.10.010}, pmid = {29336929}, issn = {1769-6690}, mesh = {Anti-Bacterial Agents/economics/therapeutic use ; Australia ; Case-Control Studies ; Clostridium Infections/diagnosis/*economics/therapy ; Cohort Studies ; Colonoscopy/economics ; Cost of Illness ; Cost-Benefit Analysis ; Decision Support Techniques ; Disease Management ; Drug Costs ; Europe ; Hospitalization/economics ; Humans ; Length of Stay/economics ; Meta-Analysis as Topic ; Multicenter Studies as Topic ; North America ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridium difficile infection (CDI) is the most important cause of healthcare-associated infectious diarrhea in industrialized countries. We performed a literature review of the overall economic burden of initial and recurrent CDI as well as of the cost-effectiveness of the various treatment strategies applied in these settings. Even though analysis of health economic data is complicated by the limited comparability of results, our review identified several internationally consistent results. Authors from different countries have shown that recurrent CDI disproportionally contributes to the overall economic burden of CDI and therefore offers considerable saving potential. Subsequent cost-effectiveness analyses almost exclusively identified fidaxomicin as the preferred treatment option for initial CDI and fecal microbiota transplant (FMT) for recurrent CDI. Among the various FMT protocols, optimum results were obtained using early colonoscopy-based FMT.}, }
@article {pmid29329346, year = {2018}, author = {Nycz, BT and Dominguez, SR and Friedman, D and Hilden, JM and Ir, D and Robertson, CE and Frank, DN}, title = {Evaluation of bloodstream infections, Clostridium difficile infections, and gut microbiota in pediatric oncology patients.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0191232}, pmid = {29329346}, issn = {1932-6203}, mesh = {Adolescent ; Bacteremia/*complications/microbiology ; Bacterial Proteins/genetics ; Bacterial Toxins/genetics ; Biodiversity ; Child ; Child, Preschool ; Clostridioides difficile/genetics ; Clostridium Infections/*complications/microbiology ; Cohort Studies ; Cross-Sectional Studies ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Genes, Bacterial ; Humans ; Male ; Neoplasms/*complications/*microbiology ; Predictive Value of Tests ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Young Adult ; }, abstract = {Bloodstream infections (BSI) and Clostridium difficile infections (CDI) in pediatric oncology/hematology/bone marrow transplant (BMT) populations are associated with significant morbidity and mortality. The objective of this study was to explore possible associations between altered microbiome composition and the occurrence of BSI and CDI in a cohort of pediatric oncology patients. Stool samples were collected from all patients admitted to the pediatric oncology floor from Oct.-Dec. 2012. Bacterial profiles from patient stools were determined by bacterial 16S rRNA gene profiling. Differences in overall microbiome composition were assessed by a permutation-based multivariate analysis of variance test, while differences in the relative abundances of specific taxa were assessed by Kruskal-Wallis tests. At admission, 9 of 42 patients (21%) were colonized with C. difficile, while 6 of 42 (14%) subsequently developed a CDI. Furthermore, 3 patients (7%) previously had a BSI and 6 patients (14%) subsequently developed a BSI. Differences in overall microbiome composition were significantly associated with disease type (p = 0.0086), chemotherapy treatment (p = 0.018), BSI following admission from any cause (p < 0.0001) or suspected gastrointestinal organisms (p = 0.00043). No differences in baseline microbiota were observed between individuals who did or did not subsequently develop C. difficile infection. Additionally, multiple bacterial groups varied significantly between subjects with post-admission BSI compared with no BSI. Our results suggest that differences in gut microbiota not only are associated with type of cancer and chemotherapy, but may also be predictive of subsequent bloodstream infection.}, }
@article {pmid29321764, year = {2017}, author = {Ekmekciu, I and von Klitzing, E and Neumann, C and Bacher, P and Scheffold, A and Bereswill, S and Heimesaat, MM}, title = {Fecal Microbiota Transplantation, Commensal Escherichia coli and Lactobacillus johnsonii Strains Differentially Restore Intestinal and Systemic Adaptive Immune Cell Populations Following Broad-spectrum Antibiotic Treatment.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {2430}, pmid = {29321764}, issn = {1664-302X}, abstract = {The essential role of the intestinal microbiota in the well-functioning of host immunity necessitates the investigation of species-specific impacts on this interplay. Aim of this study was to examine the ability of defined Gram-positive and Gram-negative intestinal commensal bacterial species, namely Escherichia coli and Lactobacillus johnsonii, respectively, to restore immune functions in mice that were immunosuppressed by antibiotics-induced microbiota depletion. Conventional mice were subjected to broad-spectrum antibiotic treatment for 8 weeks and perorally reassociated with E. coli, L. johnsonii or with a complex murine microbiota by fecal microbiota transplantation (FMT). Analyses at days (d) 7 and 28 revealed that immune cell populations in the small and large intestines, mesenteric lymph nodes and spleens of mice were decreased after antibiotic treatment but were completely or at least partially restored upon FMT or by recolonization with the respective bacterial species. Remarkably, L. johnsonii recolonization resulted in the highest CD4+ and CD8+ cell numbers in the small intestine and spleen, whereas neither of the commensal species could stably restore those cell populations in the colon until d28. Meanwhile less efficient than FMT, both species increased the frequencies of regulatory T cells and activated dendritic cells and completely restored intestinal memory/effector T cell populations at d28. Furthermore, recolonization with either single species maintained pro- and anti-inflammatory immune functions in parallel. However, FMT could most effectively recover the decreased frequencies of cytokine producing CD4+ lymphocytes in mucosal and systemic compartments. E. coli recolonization increased the production of cytokines such as TNF, IFN-γ, IL-17, and IL-22, particularly in the small intestine. Conversely, only L. johnsonii recolonization maintained colonic IL-10 production. In summary, FMT appears to be most efficient in the restoration of antibiotics-induced collateral damages to the immune system. However, defined intestinal commensals such as E. coli and L. johnsonii have the potential to restore individual functions of intestinal and systemic immunity. In conclusion, our data provide novel insights into the distinct role of individual commensal bacteria in maintaining immune functions during/following dysbiosis induced by antibiotic therapy thereby shaping host immunity and might thus open novel therapeutical avenues in conditions of perturbed microbiota composition.}, }
@article {pmid29316256, year = {2018}, author = {Zhang, Z and Liu, L and Tang, H and Jiao, W and Zeng, S and Xu, Y and Zhang, Q and Sun, Z and Mukherjee, A and Zhang, X and Hu, X}, title = {Immunosuppressive effect of the gut microbiome altered by high-dose tacrolimus in mice.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {18}, number = {7}, pages = {1646-1656}, doi = {10.1111/ajt.14661}, pmid = {29316256}, issn = {1600-6143}, mesh = {Animals ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects/*immunology ; Graft Rejection/etiology/*prevention &amp; control ; Graft Survival/drug effects/*immunology ; Immune Tolerance/drug effects/immunology ; Immunosuppressive Agents/*therapeutic use ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Skin Transplantation/*adverse effects ; T-Lymphocytes, Regulatory/drug effects/*immunology ; Tacrolimus/*therapeutic use ; }, abstract = {The alterations induced in gut microbiota by tacrolimus may affect immune function and organ transplantation. Mice were treated with high-dose tacrolimus for 14 days. The fecal microbiota were analyzed by pyrosequencing the 16S rRNA genes, and the effect on metabolism was predicted using the sequence data. The subgroups of T cells in the serum, gut-associated lymphoid tissue, and draining lymph nodes were determined by flow cytometry. Tacrolimus treatment significantly altered the relative abundance of Allobaculum, Bacteroides, and Lactobacillus and CD4[+] CD25[hi] FoxP3[+] regulatory T cells in the colonic mucosa and the circulation. These were significantly increased after either tacrolimus treatment or treatment by fecal microbiota transfer from tacrolimus-treated donors. Further, treatment with low-dose tacrolimus plus fecal microbiota transfer from high-dose tacrolimus-altered mice increased skin allograft survival rate in a skin transplantation model. Thus, high-dose tacrolimus alters the compositions and taxa of the gut microbiota. Administration of these conditioned gut microbiota plus low-dose tacrolimus resulted in regulation of colonic and systemic immune responses and an increased allograft survival rate. This study demonstrated a new strategy for controlling allograft rejection by combining an immunosuppressive agent with gut microbiome transplantation.}, }
@article {pmid29312905, year = {2017}, author = {Ge, T and Wang, Y and Che, Y and Xiao, Y and Zhang, T}, title = {Atypical Late-Onset Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome with Intractable Diarrhea: A Case Report.}, journal = {Frontiers in pediatrics}, volume = {5}, number = {}, pages = {267}, pmid = {29312905}, issn = {2296-2360}, abstract = {Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare life threatening congenital autoimmune disorder caused by mutations in the forkhead box protein 3 (FOXP3) gene. The main typical clinical manifestations of IPEX are enteropathy, type 1 diabetes mellitus, and skin diseases, which usually appear in the first months of life and cause death without treatment. Here, we report a 6-year-old boy with late-onset IPEX syndrome due to a c.1190G>A (p. R397Q) mutation in exon 11 of the FOXP3 gene. The boy had intractable diarrhea, abdominal pain, recurrent infections, and failure to thrive. However, diabetes and skin diseases were not observed in the patient. The patient was received metronidazole, teicoplanin, fluconazole, mycamine, ceftriaxone, azithromycin, and fecal microbiota transplantation for treating infections, methylprednisolone and infliximab for suspicion of Crohn's disease after admission. Finally, the boy was diagnosed as IPEX syndrome by genetic test and received hematopoietic stem cell transplantation (HSCT). Our findings suggests that IPEX should be considered in cases of late-onset, mild forms, and less typical clinical manifestations to avoid diagnostic delay.}, }
@article {pmid29312263, year = {2017}, author = {von Klitzing, E and Ekmekciu, I and Bereswill, S and Heimesaat, MM}, title = {Intestinal and Systemic Immune Responses upon Multi-drug Resistant Pseudomonas aeruginosa Colonization of Mice Harboring a Human Gut Microbiota.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {2590}, pmid = {29312263}, issn = {1664-302X}, abstract = {The World Health Organization has rated multi-drug resistant (MDR) Pseudomonas aeruginosa as serious threat for human health. It is, however, unclear, whether intestinal MDR P. aeruginosa carriage is associated with inflammatory responses in intestinal or even systemic compartments. In the present study, we generated with respect to their microbiota "humanized" mice by human fecal microbiota transplantation of secondary abiotic mice. Following peroral challenge with a clinical P. aeruginosa isolate on two consecutive days, mice harboring a human or murine microbiota were only partially protected from stable intestinal P. aeruginosa colonization given that up to 78% of mice were P. aeruginosa-positive at day 28 post-infection (p.i.). Irrespective of the host-specificity of the microbiota, P. aeruginosa colonized mice were clinically uncompromised. However, P. aeruginosa colonization resulted in increased intestinal epithelial apoptosis that was accompanied by pronounced proliferative/regenerative cell responses. Furthermore, at day 7 p.i. increased innate immune cell populations such as macrophages and monocytes could be observed in the colon of mice harboring either a human or murine microbiota, whereas this held true at day 28 p.i. for adaptive immune cells such as B lymphocytes in both the small and large intestines of mice with murine microbiota. At day 7 p.i., pro-inflammatory cytokine secretion was enhanced in the colon and mesenteric lymph nodes, whereas the anti-inflammatory cytokine IL-10 was down-regulated in the former at day 28 p.i. Strikingly, cytokine responses upon intestinal P. aeruginosa colonization were not restricted to the intestinal tract, but could also be observed systemically, given that TNF and IFN-γ concentrations were elevated in spleens as early as 7 days p.i., whereas splenic IL-10 levels were dampened at day 28 p.i. of mice with human microbiota. In conclusion, mere intestinal carriage of MDR P. aeruginosa by clinically unaffected mice results in pro-inflammatory sequelae not only in intestinal, but also systemic compartments.}, }
@article {pmid29311138, year = {2018}, author = {Gao, XJ and Li, T and Wei, B and Yan, ZX and Hu, N and Huang, YJ and Han, BL and Wai, TS and Yang, W and Yan, R}, title = {Bacterial Outer Membrane Vesicles from Dextran Sulfate Sodium-Induced Colitis Differentially Regulate Intestinal UDP-Glucuronosyltransferase 1A1 Partially Through Toll-Like Receptor 4/Mitogen-Activated Protein Kinase/Phosphatidylinositol 3-Kinase Pathway.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {46}, number = {3}, pages = {292-302}, doi = {10.1124/dmd.117.079046}, pmid = {29311138}, issn = {1521-009X}, mesh = {Animals ; Bacterial Outer Membrane Proteins/*metabolism ; Caco-2 Cells ; Colitis/*metabolism ; Colon/metabolism ; Dextran Sulfate/*metabolism ; Gastrointestinal Microbiome/physiology ; Glucuronosyltransferase/*metabolism ; Humans ; Male ; Mitogen-Activated Protein Kinases/*metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4/*metabolism ; }, abstract = {UDP-glucuronosyltransferase 1A1 (UGT1A1) constitutes an important part of intestinal epithelial barrier and catalyzes glucuronidation of many endogenous compounds and drugs. Downregulation of UGT1A1 in inflammation has been reported, whereas the association with gut dysbiosis is poorly defined. This study verified the involvement of gut microbiota in intestinal UGT1A1 regulation using dextran sulfate sodium (DSS)-induced rat colitis model plus fecal microbiota transplantation (FMT). Generally, both DSS induction and colitis-to-normal FMT suppressed mRNA and protein expressions of UGT1A1 and nuclear xenobiotic receptors (NRs) in colon, but enhanced mRNA and decreased protein of rat UGT1A1/rat NRs in small intestine. Normal-to-colitis FMT alleviated DSS-induced changes. Bacterial outer membrane vesicles (OMVs) from colitis rats and rats receiving colitis feces reduced both mRNA and protein of human UGT1A1 (hUGT1A1)/human NRs (hNRs) in Caco-2 cells. Interestingly, using deoxycholate to reduce lipopolysaccharide, normal OMVs upregulated hUGT1A1/hNRs, whereas colitis OMVs decreased, indicating the involvement of other OMVs components in UGT1A1 regulation. The 10- to 50-kDa fractions from both normal and colitis OMVs downregulated hUGT1A1, human PXR, and human PPAR-γ, whereas >50-kDa fractions from normal rats upregulated hUGT1A1 and human CAR. Additionally, the conditioned medium from OMVs-stimulated rat primary macrophages also reduced hUGT1A1/hNRs expression. Both Toll-like receptor (TLR)2 and TLR4 were activated by DSS, colitis-to-normal FMT, and the opposite, whereas only TLR4 was increased in OMVs-treated cells. TLR4 small interfering RNA blocked hUGT1A1/hNRs downregulation and phosphatidylinositol 3-kinase/Akt, extracellular signal-regulated kinase, and nuclear factor κB phosphorylation evoked by bacterial OMVs. Taken together, this study demonstrated that gut microbiota regulate intestinal UGT1A1 partially through secreting OMVs, which interact with intestinal epithelial cells directly or via activating macrophage.}, }
@article {pmid29311119, year = {2018}, author = {Clemente, JC and Manasson, J and Scher, JU}, title = {The role of the gut microbiome in systemic inflammatory disease.}, journal = {BMJ (Clinical research ed.)}, volume = {360}, number = {}, pages = {j5145}, pmid = {29311119}, issn = {1756-1833}, support = {K23 AR064318/AR/NIAMS NIH HHS/United States ; R03 AR072182/AR/NIAMS NIH HHS/United States ; S10 OD018522/OD/NIH HHS/United States ; T32 AR069515/AR/NIAMS NIH HHS/United States ; }, mesh = {Autoimmune Diseases/immunology/*microbiology ; Fecal Microbiota Transplantation/methods ; Feeding Behavior/*physiology ; Gastrointestinal Microbiome/*immunology/physiology ; Humans ; Inflammation/immunology/*microbiology ; Inflammatory Bowel Diseases/immunology/*microbiology/pathology ; Microbiota ; Mucous Membrane/immunology/*microbiology ; Prebiotics ; Probiotics ; }, abstract = {The role of the gut microbiome in models of inflammatory and autoimmune disease is now well characterized. Renewed interest in the human microbiome and its metabolites, as well as notable advances in host mucosal immunology, has opened multiple avenues of research to potentially modulate inflammatory responses. The complexity and interdependence of these diet-microbe-metabolite-host interactions are rapidly being unraveled. Importantly, most of the progress in the field comes from new knowledge about the functional properties of these microorganisms in physiology and their effect in mucosal immunity and distal inflammation. This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect our understanding of wellness and disease, particularly in autoimmunity.}, }
@article {pmid29309934, year = {2018}, author = {Ooijevaar, RE and van Beurden, YH and Terveer, EM and Goorhuis, A and Bauer, MP and Keller, JJ and Mulder, CJJ and Kuijper, EJ}, title = {Update of treatment algorithms for Clostridium difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {24}, number = {5}, pages = {452-462}, doi = {10.1016/j.cmi.2017.12.022}, pmid = {29309934}, issn = {1469-0691}, mesh = {Algorithms ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Clinical Trials as Topic ; Clostridioides difficile/*drug effects/physiology ; Clostridium Infections/*microbiology/*therapy ; Disease Management ; Drug Discovery ; Fecal Microbiota Transplantation ; Humans ; Practice Guidelines as Topic ; }, abstract = {BACKGROUND: Clostridium difficile is the leading cause of antibiotic-associated diarrhoea, both in healthcare facilities and in the community. The recurrence rate of C. difficile infection (CDI) remains high, up to 20%. Since the publication of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidance document on CDI treatment in 2014, new therapeutic approaches have been developed and tested to achieve higher sustained clinical cure in CDI.<br><br>AIM: To review novel treatments and approaches for CDI, except probiotics and vaccines. We focused on new antibiotics, antibiotic inactivators, monoclonal antibodies and gut microbiota modulating therapies.<br><br>SOURCES: A literature review was performed for clinical trials published in PubMed, Embase or Cochrane Library between January 2013 and November 2017.<br><br>CONTENT: We analysed 28 clinical trials and identified 14 novel agents. Completed phase 2 studies were found for cadazolid, LFF571, ridinilazole and nontoxigenic C.&#xa0;difficile strains. Four phase 3 active comparator studies comparing vancomycin with bezlotoxumab, surotomycin (n&#xa0;=&#xa0;2) and rifaximin have been published. Seven clinical trials for treatment of multiple recurrent CDI with faecal microbiota transplantation were analysed, describing faecal microbiota transplantation by upper or lower gastrointestinal route (n&#xa0;=&#xa0;5) or by capsules (n&#xa0;=&#xa0;2).<br><br>IMPLICATIONS: Metronidazole is mentioned in the ESCMID guideline as first-line therapy, but we propose that oral vancomycin will become the first choice when antibiotic treatment for CDI is necessary. Fidaxomicin is a good alternative, especially in patients at risk of relapse. Vancomycin combined with faecal microbiota transplantation remains the primary therapy for multiple recurrent CDI. We anticipate that new medication that protects the gut microbiota will be further developed and tested to prevent CDI during antibiotic therapy.}, }
@article {pmid29300048, year = {2018}, author = {Dickson, I}, title = {Therapy: Oral capsule FMT effective for C. difficile infection.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {15}, number = {2}, pages = {68}, pmid = {29300048}, issn = {1759-5053}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Colonoscopy ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid29299467, year = {2017}, author = {Juncadella, AC and Moss, A}, title = {Fecal microbiota transplantation as a possible treatment of irritable bowel syndrome.}, journal = {Annals of translational medicine}, volume = {5}, number = {24}, pages = {506}, pmid = {29299467}, issn = {2305-5839}, }
@article {pmid29299452, year = {2017}, author = {Craven, LJ and Silverman, M and Burton, JP}, title = {Transfer of altered behaviour and irritable bowel syndrome with diarrhea (IBS-D) through fecal microbiota transplant in mouse model indicates need for stricter donor screening criteria.}, journal = {Annals of translational medicine}, volume = {5}, number = {24}, pages = {490}, pmid = {29299452}, issn = {2305-5839}, }
@article {pmid29293148, year = {2018}, author = {Arulkumaran, N and Pollen, S and Greco, E and Courtneidge, H and Hall, AM and Duchen, MR and Tam, FWK and Unwin, RJ and Singer, M}, title = {Renal Tubular Cell Mitochondrial Dysfunction Occurs Despite Preserved Renal Oxygen Delivery in Experimental Septic Acute Kidney Injury.}, journal = {Critical care medicine}, volume = {46}, number = {4}, pages = {e318-e325}, pmid = {29293148}, issn = {1530-0293}, support = {//Wellcome Trust/United Kingdom ; 093969//Wellcome Trust/United Kingdom ; }, mesh = {Acute Kidney Injury/*physiopathology ; Animals ; Cell Survival ; Disease Models, Animal ; Kidney Function Tests ; Kidney Tubules/metabolism ; Male ; Membrane Potential, Mitochondrial/physiology ; Mitochondria/*metabolism ; NAD/metabolism ; Oxygen/*blood ; Oxygen Consumption ; Prospective Studies ; Rats ; Rats, Wistar ; Reactive Oxygen Species/metabolism ; Renal Circulation ; Sepsis/*physiopathology ; }, abstract = {OBJECTIVE: To explain the paradigm of significant renal functional impairment despite preserved hemodynamics and histology in sepsis-induced acute kidney injury.<br><br>DESIGN: Prospective observational animal study.<br><br>SETTING: University research laboratory.<br><br>SUBJECTS: Male Wistar rats.<br><br>INTERVENTION: Using a fluid-resuscitated sublethal rat model of fecal peritonitis, changes in renal function were characterized in relation to global and renal hemodynamics, and histology at 6 and 24 hours (n = 6-10). Sham-operated animals were used as comparison (n = 8). Tubular cell mitochondrial function was assessed using multiphoton confocal imaging of live kidney slices incubated in septic serum.<br><br>MEASUREMENTS AND MAIN RESULTS: By 24 hours, serum creatinine was significantly elevated with a concurrent decrease in renal lactate clearance in septic animals compared with sham-operated and 6-hour septic animals. Renal uncoupling protein-2 was elevated in septic animals at 24 hours although tubular cell injury was minimal and mitochondrial ultrastructure in renal proximal tubular cells preserved. There was no significant change in global or renal hemodynamics and oxygen delivery/consumption between sham-operated and septic animals at both 6- and 24-hour timepoints. In the live kidney slice model, mitochondrial dysfunction was seen in proximal tubular epithelial cells incubated with septic serum with increased production of reactive oxygen species, and decreases in nicotinamide adenine dinucleotide and mitochondrial membrane potential. These effects were prevented by coincubation with the reactive oxygen species scavenger, 4-hydroxy-2,2,6,6-tetramethyl-piperidin-1-oxyl.<br><br>CONCLUSIONS: Renal dysfunction in sepsis occurs independently of hemodynamic instability or structural damage. Mitochondrial dysfunction mediated by circulating mediators that induce local oxidative stress may represent an important pathophysiologic mechanism.}, }
@article {pmid29290760, year = {2017}, author = {Scott, AJ and Merrifield, CA and Alexander, JL and Marchesi, JR and Kinross, JM}, title = {Highlights from the Inaugural International Cancer Microbiome Consortium Meeting (ICMC), 5-6 September 2017, London, UK.}, journal = {Ecancermedicalscience}, volume = {11}, number = {}, pages = {791}, pmid = {29290760}, issn = {1754-6605}, abstract = {The International Cancer Microbiome Consortium (ICMC) is a recently launched collaborative between academics and academic-clinicians that aims to promote microbiome research within the field of oncology, establish expert consensus and deliver education for academics and clinicians. The inaugural two-day meeting was held at the Royal Society of Medicine (RSM), London, UK, 5-6 September 2017. Microbiome and cancer experts from around the world first delivered a series of talks during an educational day and then sat for a day of roundtable discussion to debate key topics in microbiome-cancer research. Talks delivered during the educational day covered a broad range of microbiome-related topics. The potential role of the microbiome in the pathogenesis of colorectal cancer was discussed and debated in detail with experts highlighting the latest data in animal models and humans and addressing the question of causation versus association. The impact of the microbiota on other cancers-such as lung and urogenital tract-was also discussed. The microbiome represents a novel target for therapeutic manipulation in cancer and a number of talks explored how this might be realised through diet, faecal microbiota transplant and chemotherapeutics. On the second day, experts debated pre-agreed topics with the aim of producing a consensus statement with a focus on the current state of our knowledge and key gaps for further development. The panel debated the notion of a 'healthy' microbiome and, in turn, the concept of dysbiosis in cancer. The mechanisms of microbiota-induced carcinogenesis were discussed in detail and our current conceptual models were assessed. Experts also considered co-factors in microbiome-induced carcinogenesis to conclude that the tripartite 'interactome' between genetically vulnerable host, environment and the microbiome is central to our current understanding. To conclude, the roundtable discussed how the microbiome may be exploited for therapeutic benefit in cancer and the safety implications of performing such research in oncology patients.}, }
@article {pmid29290658, year = {2017}, author = {Zhang, J and Ren, FG and Liu, P and Zhang, HK and Zhu, HY and Feng, Z and Zhang, XF and Wang, B and Liu, XM and Zhang, XG and Wu, RQ and Lv, Y}, title = {Characteristics of fecal microbial communities in patients with non-anastomotic biliary strictures after liver transplantation.}, journal = {World journal of gastroenterology}, volume = {23}, number = {46}, pages = {8217-8226}, pmid = {29290658}, issn = {2219-2840}, mesh = {Adult ; Bacteria/genetics/*isolation &amp; purification/pathogenicity ; Biliary Tract Diseases/etiology/*microbiology ; Constriction, Pathologic/etiology/microbiology ; DNA, Bacterial/isolation &amp; purification ; Dysbiosis/etiology/microbiology ; End Stage Liver Disease/surgery ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Liver Transplantation/*adverse effects ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {AIM: To explore the possible relationship between fecal microbial communities and non-anastomotic stricture (NAS) after liver transplantation (LT).<br><br>METHODS: A total of 30 subjects including 10 patients with NAS, 10 patients with no complications after LT, and 10 non-LT healthy individuals were enrolled. Fecal microbial communities were assessed by the 16S rRNA gene sequencing technology.<br><br>RESULTS: Different from the uncomplicated and healthy groups, unbalanced fecal bacterium ratio existed in patients with NAS after LT. The results showed that NAS patients were associated with a decrease of Firmicutes and Bacteroidetes and an increase of Proteobacteria at the phylum level, with the proportion-ratio imbalance between potential pathogenic families including Enterococcaceae, Streptococcaceae, Enterobacteriaceae, Pseudomonadaceae and dominant families including Bacteroidaceae.<br><br>CONCLUSION: The compositional shifts of the increase of potential pathogenic bacteria as well as the decrease of dominant bacteria might contribute to the incidence of NAS.}, }
@article {pmid29288655, year = {2017}, author = {Gini, A and Zauber, AG and Cenin, DR and Omidvari, AH and Hempstead, SE and Fink, AK and Lowenfels, AB and Lansdorp-Vogelaar, I}, title = {Cost-Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2017.12.011}, pmid = {29288655}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared to the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis.<br><br>METHODS: We adjusted the existing Microsimulation Screening Analysis-Colon microsimulation model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess whether optimal screening strategies would change.<br><br>RESULTS: Colonoscopy every 5 years, starting at age 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in population is not clear.<br><br>CONCLUSIONS: Using a Microsimulation Screening Analysis-Colon microsimulation model, we found screening of patients with cystic fibrosis for CRC to be cost-effective. Due to the higher risk in these patients for CRC, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis.}, }
@article {pmid29285689, year = {2018}, author = {Nishida, A and Inoue, R and Inatomi, O and Bamba, S and Naito, Y and Andoh, A}, title = {Gut microbiota in the pathogenesis of inflammatory bowel disease.}, journal = {Clinical journal of gastroenterology}, volume = {11}, number = {1}, pages = {1-10}, pmid = {29285689}, issn = {1865-7265}, mesh = {Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Immunity, Innate ; Inflammatory Bowel Diseases/*microbiology/therapy ; Nutritional Physiological Phenomena ; Probiotics/therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic and relapsing inflammatory disorder of the intestine. Although its incidence is increasing globally, the precise etiology remains unclear and a cure for IBD has yet to be discovered. The most accepted hypothesis of IBD pathogenesis is that complex interactions between genetics, environmental factors, and the host immune system lead to aberrant immune responses and chronic intestinal inflammation. The human gut harbors a complex and abundant aggregation of microbes, collectively referred to as the gut microbiota. The gut microbiota has physiological functions associated with nutrition, the immune system, and defense of the host. Recent advances in next-generation sequencing technology have identified alteration of the composition and function of the gut microbiota, which is referred to as dysbiosis, in IBD. Clinical and experimental data suggest dysbiosis may play a pivotal role in the pathogenesis of IBD. This review is focused on the physiological function of the gut microbiota and the association between the gut microbiota and pathogenesis in IBD. In addition, we review the therapeutic options for manipulating the altered gut microbiota, such as probiotics and fecal microbiota transplantation.}, }
@article {pmid29280116, year = {2017}, author = {Zhang, X and Tian, H and Ma, C and Yang, B and Hua, Y and Zhu, Y and Gu, L and Li, N}, title = {[Efficacy observation of periodic fecal microbiota transplantation in the treatment of refractory constipation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {20}, number = {12}, pages = {1355-1359}, pmid = {29280116}, issn = {1671-0274}, mesh = {Constipation/*therapy ; Defecation ; *Fecal Microbiota Transplantation ; Humans ; Quality of Life ; Retrospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate the efficacy of periodic fecal microbiota transplantation (FMT) for refractory constipation.<br><br>METHODS: Clinical data of 49 patients with refractory constipation undergoing FMT through standard transplantation path of nasojejunal tube between April 2015 and April 2016 in Intestinal Microenvironment Treatment Centre of Nanjing General Hospital were analyzed retrospectively. Of 49 patients, 25 received single FMT for only 6 days (single group), and 24 received periodic FMT with another 6 days FMT 1 month after the first 6 days FMT (periodic group). The follow up was at 12 weeks after treatment. Autonomous defecation frequency, Wexner constipation score, gastrointestinal quality of life index and related adverse reaction were evaluated and compared at 4-, 8- and 12-week after treatment. Statistical analysis was performed on the difference after treatment at each time point, and the greater difference indicated the better improvement.<br><br>RESULTS: There were no statistically significant differences in general characteristics between the two groups (all P<0.05). Before treatment, Wexner constipation score was 17.32&#xb1;2.66 and 16.25&#xb1;2.47, gastrointestinal quality of life index was 81.84&#xb1;8.73 and 83.25&#xb1;7.87, autonomous defecation frequency was (1.64&#xb1;0.57) time/week and (1.42&#xb1;0.65) time/week in single group and periodic group respectively, whose differences were not significant (all P>0.05). Compared with before FMT treatment, the autonomous defecation frequency, Wexner constipation score, gastrointestinal quality of life index were obviously improved at the 4-, 8-, 12-week (all P=0.000). At the 4-week after FMT treatment, the improvement degree of autonomous defecation frequency, Wexner constipation score, gastrointestinal quality of life index was compared between two groups, and no statistically significant differences were found (all P>0.05). While at 8-week and 12-week after FMT treatment, as compared to single group, periodic group had greater Wexner constipation score (at 8-week: 7.29&#xb1;2.05 vs. 5.96&#xb1;2.30, t=2.135, P=0.038; at 12-week: 7.21&#xb1;1.98 vs. 5.80&#xb1;2.43, t=2.218, P=0.031), greater gastrointestinal quality of life index (at 8-week: 25.71&#xb1;8.91 vs. 20.20&#xb1;8.53, t=2.211, P=0.032; at 12-week: 24.16&#xb1;8.99 vs. 18.92&#xb1;8.28, t=2.127, P=0.039) and better autonomous defecation frequency [at 8-week: (2.42&#xb1;0.93) time/week vs. (1.72&#xb1;0.61) time/week, t=3.110, P=0.003; at 12-week: (1.37&#xb1;0.88) time/week vs. (0.84&#xb1;0.62) time/week, t=2.454, P=0.018].<br><br>CONCLUSION: Periodic FMT has better efficacy than single FMT in the treatment of refractory constipation.}, }
@article {pmid29278509, year = {2017}, author = {Kang, Y and Cai, Y}, title = {Gut microbiota and obesity: implications for fecal microbiota transplantation therapy.}, journal = {Hormones (Athens, Greece)}, volume = {16}, number = {3}, pages = {223-234}, doi = {10.14310/horm.2002.1742}, pmid = {29278509}, issn = {2520-8721}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Metabolic Syndrome/*microbiology/*therapy ; Obesity/*microbiology/*therapy ; }, abstract = {Obesity is a major public health issue as it is causally associated with several chronic disorders, including type-2 diabetes, cerebrovascular disease (CVD), and cancer. In the United States and other countries worldwide, the obesity epidemic has drastically impacted the status of health of millions as well as healthcare costs. Aside from poor diet, hygiene, and genetics, there are many other factors thought to play an important role in the emergence of obesity. Nowadays, accumulating evidence is elucidating the relation of dysbiosis of intestinal bacteria with obesity and metabolic disorders. Certain gut microbial strains have been shown to inhibit or attenuate immune responses related to chronic inflammation in experimental models, suggesting that specific species among gut microbiota may play either a protective or a pathogenic role in the progression of obesity. Fecal microbiota transplantation (FMT) can therefore represent a therapeutic approach for obesity treatment. FMT is a relatively straightforward therapy that manipulates the human gastrointestinal (GI) microbiota by transferring healthy donor microbiota into an existing but disturbed microbial ecosystem. However, the relevant scientific work is still in its early stages. In this review, we summarize the cutting-edge research being done into FMT treatment of obesity, current issues in FMT treatment, and the future of FMT and microbial therapeutics.}, }
@article {pmid29277311, year = {2018}, author = {Yang, Y and Tian, J and Yang, B}, title = {Targeting gut microbiome: A novel and potential therapy for autism.}, journal = {Life sciences}, volume = {194}, number = {}, pages = {111-119}, doi = {10.1016/j.lfs.2017.12.027}, pmid = {29277311}, issn = {1879-0631}, mesh = {Animals ; Autism Spectrum Disorder/*microbiology/pathology/*therapy ; Brain/pathology ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Probiotics/*therapeutic use ; }, abstract = {Autism spectrum disorder (ASD) is a severely neurodevelopmental disorder that impairs a child's ability to communicate and interact with others. Children with neurodevelopmental disorder, including ASD, are regularly affected by gastrointestinal problems and dysbiosis of gut microbiota. On the other hand, humans live in a co-evolutionary association with plenty of microorganisms that resident on the exposed and internal surfaces of our bodies. The microbiome, refers to the collection of microbes and their genetic material, confers a variety of physiologic benefits to the host in many key aspects of life as well as being responsible for some diseases. A large body of preclinical literature indicates that gut microbiome plays an important role in the bidirectional gut-brain axis that communicates between the gut and central nervous system. Moreover, accumulating evidences suggest that the gut microbiome is involved in the pathogenesis of ASD. The present review introduces the increasing evidence suggesting the reciprocal interaction network among microbiome, gut and brain. It also discusses the possible mechanisms by which gut microbiome influences the etiology of ASD via altering gut-brain axis. Most importantly, it highlights the new findings of targeting gut microbiome, including probiotic treatment and fecal microbiota transplant, as novel and potential therapeutics for ASD diseases.}, }
@article {pmid29276171, year = {2018}, author = {Schroeder, BO and Birchenough, GMH and Ståhlman, M and Arike, L and Johansson, MEV and Hansson, GC and Bäckhed, F}, title = {Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration.}, journal = {Cell host &amp; microbe}, volume = {23}, number = {1}, pages = {27-40.e7}, pmid = {29276171}, issn = {1934-6069}, support = {615362/ERC_/European Research Council/International ; 694181/ERC_/European Research Council/International ; U01 AI095473/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bifidobacterium longum/*metabolism ; Colon/*microbiology/pathology ; Diet, Western/*adverse effects ; Dietary Fiber/*therapeutic use ; Dietary Supplements ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Intestinal Mucosa/*microbiology/pathology ; Inulin/therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/pathology ; }, abstract = {Diet strongly affects gut microbiota composition, and gut bacteria can influence the colonic mucus layer, a physical barrier that separates trillions of gut bacteria from the host. However, the interplay between a Western style diet (WSD), gut microbiota composition, and the intestinal mucus layer is less clear. Here we show that mice fed a WSD have an altered colonic microbiota composition that causes increased penetrability and a reduced growth rate of the inner mucus layer. Both barrier defects can be prevented by transplanting microbiota from chow-fed mice. In addition, we found that administration of Bifidobacterium longum was sufficient to restore mucus growth, whereas administration of the fiber inulin prevented increased mucus penetrability in WSD-fed mice. We hypothesize that the presence of distinct bacteria is crucial for proper mucus function. If confirmed in humans, these findings may help to better understand diseases with an affected mucus layer, such as ulcerative colitis.}, }
@article {pmid29274895, year = {2018}, author = {Lifschitz, C and Sieczkowska, A}, title = {New insights into the fecal microbiota of children living in a slum: association with small bowel bacterial overgrowth.}, journal = {Jornal de pediatria}, volume = {94}, number = {5}, pages = {455-457}, doi = {10.1016/j.jped.2017.12.002}, pmid = {29274895}, issn = {1678-4782}, mesh = {Bacteria/*growth &amp; development ; Biomarkers/analysis ; Breath Tests ; Child ; Feces/*microbiology ; Female ; Humans ; Hydrogen/*analysis ; Intestine, Small/metabolism/*microbiology ; Male ; Methane/*analysis ; *Microbiota ; Poverty Areas ; }, }
@article {pmid29272955, year = {2018}, author = {Engsbro, AL and Nielsen, KL and Hornum, M and Andersen, LP}, title = {Laribacter hongkongensis: clinical presentation, epidemiology and treatment. A review of the literature and report of the first case in Denmark.}, journal = {Infectious diseases (London, England)}, volume = {50}, number = {6}, pages = {417-422}, doi = {10.1080/23744235.2017.1419373}, pmid = {29272955}, issn = {2374-4243}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Denmark ; Diarrhea/etiology/*microbiology ; Drug Resistance, Bacterial ; Feces/microbiology ; Female ; *Food Microbiology ; Genome, Bacterial/genetics ; Humans ; Microbial Sensitivity Tests ; Neisseriaceae/drug effects/*physiology ; *Neisseriaceae Infections/complications/drug therapy/epidemiology/pathology ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; Transplant Recipients ; Young Adult ; }, abstract = {BACKGROUND: Laribacter hongkongensis is an emerging pathogen related to gastroenteritis that can cause invasive and even fatal disease. The aim of this review is to describe the clinical presentation, epidemiology, treatment options and implications for the clinical microbiology laboratory.<br><br>METHODS: We searched Pubmed using the term Laribacter hongkongensis with limitations human and language English, and identified 35 publications with eight reports on human cases.<br><br>RESULTS: We describe our first case of prolonged, travel-related gastroenteritis where Laribacter hongkongensis was isolated as the sole pathogen. Our review suggests that L. hongkongensis causes non-bloody acute diarrhoea with potential for invasive disease, since three cases of bacteraemia and one case of dialysis related peritonitis have been described previously. L. hongkongensis has primarily been described in Asia, but reports from Europe, North America and Australia suggests a worldwide distribution. Broad culturing with subsequent identification by the MALDI-TOF is the current strategy for detection of L. hongkongensis. Phenotypic susceptibility testing is necessary to guide the treatment choice. Few resistance genes have been described in L. hongkongensis.<br><br>CONCLUSION: L. hongkongensis should be considered a potential cause of acute and prolonged diarrhoea. Clinicians must be aware of the test methods in the local clinical microbiology laboratory, since L. hongkongensis is difficult to detect and easily overlooked.}, }
@article {pmid29272401, year = {2018}, author = {Mamo, Y and Woodworth, MH and Wang, T and Dhere, T and Kraft, CS}, title = {Durability and Long-term Clinical Outcomes of Fecal Microbiota Transplant Treatment in Patients With Recurrent Clostridium difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {11}, pages = {1705-1711}, pmid = {29272401}, issn = {1537-6591}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) appears safe and effective for treatment of recurrent Clostridium difficile infection (RCDI). However, durability, long-term clinical outcomes, and patient satisfaction after FMT are not well described.<br><br>METHODS: Eligible patients who received FMT for RCDI at Emory Hospital between 1 July 2012 and 31 December 2016 were contacted via telephone for a follow-up survey. Of 190 eligible patients, 137 (72%) completed the survey.<br><br>RESULTS: Median time from last FMT to follow-up was 22 months. Overall, 82% (113/137) of patients at follow-up had no recurrence of C. difficile infection (CDI) post-FMT (non-RCDI group) and 18% (24/137) of patients had CDI post-FMT (RCDI group). Antibiotic exposure for non-CDI infections after FMT was more common in the RCDI group compared to the non-RCDI group (75% vs 38%, P = .0009). Overall, 11% of patients reported improvement or resolution of diagnoses not related to CDI post-FMT, and 33% reported development of a new medical condition or symptom post-FMT. Ninety-five percent of patients (122/128) indicated that they would undergo FMT again, and 70% of these 122 reported that they would prefer FMT to antibiotics as initial treatment if they were to have a CDI recurrence.<br><br>CONCLUSIONS: In this follow-up survey of outcomes after FMT at a median of 22 months follow-up, 82% of patients had durable cure of CDI. Patients with recurrence had more post-FMT antibiotic exposure, underscoring the need for thoughtful antibiotic use and a potential role for prophylactic microbiome enrichment to reduce recurrence.}, }
@article {pmid29272397, year = {2018}, author = {Leung, V and Vincent, C and Edens, TJ and Miller, MA and Manges, AR}, title = {Reply to Davido et al.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {8}, pages = {1317-1318}, doi = {10.1093/cid/cix964}, pmid = {29272397}, issn = {1537-6591}, mesh = {Anti-Bacterial Agents ; *Anti-Infective Agents ; *Clostridium Infections ; Drug Resistance, Bacterial ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid29272347, year = {2018}, author = {Davido, B and Salomon, J and Lawrence, C and Duran, C and Batista, R and de Truchis, P and Dinh, A}, title = {Impact of Fecal Microbiota Transplantation for Decolonization of Multidrug-Resistant Organisms May Vary According to Donor Microbiota.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {8}, pages = {1316-1317}, doi = {10.1093/cid/cix963}, pmid = {29272347}, issn = {1537-6591}, mesh = {Anti-Bacterial Agents ; *Clostridium Infections ; Drug Resistance, Bacterial ; Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid29271225, year = {2018}, author = {Sebastián Domingo, JJ and Sánchez Sánchez, C}, title = {From the intestinal flora to the microbiome.}, journal = {Revista espanola de enfermedades digestivas}, volume = {110}, number = {1}, pages = {51-56}, doi = {10.17235/reed.2017.4947/2017}, pmid = {29271225}, issn = {1130-0108}, mesh = {Gastroenterology/*history ; Gastrointestinal Diseases/microbiology ; *Gastrointestinal Microbiome ; History, 17th Century ; History, 19th Century ; Humans ; Intestines/*microbiology ; }, abstract = {In this article, the history of the microbiota is reviewed and the related concepts of the microbiota, microbiome, metagenome, pathobiont, dysbiosis, holobiont, phylotype and enterotype are defined. The most precise and current knowledge about the microbiota is presented and the metabolic, nutritional and immunomodulatory functions are reviewed. Some gastrointestinal diseases whose pathogenesis is associated with the intestinal microbiota, including inflammatory bowel disease, irritable bowel syndrome and celiac disease, among others, are briefly discussed. Finally, some prominent and promising data with regard to the fecal microbiota transplantation in certain digestive illness are discussed.}, }
@article {pmid29270794, year = {2018}, author = {Qin, C and Zhang, H and Zhao, L and Zeng, M and Huang, W and Fu, G and Zhou, W and Wang, H and Yan, H}, title = {Microbiota transplantation reveals beneficial impact of berberine on hepatotoxicity by improving gut homeostasis.}, journal = {Science China. Life sciences}, volume = {61}, number = {12}, pages = {1537-1544}, doi = {10.1007/s11427-017-9202-0}, pmid = {29270794}, issn = {1869-1889}, mesh = {Animals ; Berberine/*pharmacology/*therapeutic use ; Chemical and Drug Induced Liver Injury/*therapy ; Disease Models, Animal ; Dysbiosis/chemically induced/*drug therapy/*microbiology ; Fecal Microbiota Transplantation/*standards ; Gastrointestinal Microbiome/drug effects ; Homeostasis ; Intestines/*drug effects/microbiology/physiology ; Male ; Mice, Inbred C57BL ; Rats, Sprague-Dawley ; }, abstract = {Berberine has been shown to reduce acute liver injury although the underlying mechanism is not fully understood. Because of the anatomic connection, the liver is constantly exposed to gut-derived bacterial products and metabolites. In this study, we showed that berberine has beneficial effects on both hepatotoxicity and intestinal damage in a rat model of chronic or acute liver injury. Microbiota transplantation from the rats with chronic hepatotoxicity could aggravate acute hepatotoxicity in mice treated with diethylnitrosamine (DEN). In rat models with gut homeostasis disruption induced by penicillin or dextran sulfate sodium (DSS), their fecal microbiota could also cause an enhanced hepatotoxicity of recipient mice. When treated with berberine, the DSS-induced enteric dysbacteriosis could be mitigated and their fecal bacteria were able to reduce acute hepatotoxicity in recipient mice. This study indicates that berberine could improve intestinal dysbacteriosis, which reduces the hepatotoxicity caused by pathological or pharmacological intervention. Fecal microbiota transplantation might be a useful method to directly explore homeostatic alteration in gut microbiota.}, }
@article {pmid29269310, year = {2018}, author = {Lin, JA and Wu, CH and Yen, GC}, title = {Methylglyoxal displays colorectal cancer-promoting properties in the murine models of azoxymethane and CT26 isografts.}, journal = {Free radical biology &amp; medicine}, volume = {115}, number = {}, pages = {436-446}, doi = {10.1016/j.freeradbiomed.2017.12.020}, pmid = {29269310}, issn = {1873-4596}, mesh = {Animals ; Azoxymethane/toxicity ; Carcinogenesis ; Carcinogens/*administration &amp; dosage ; Cell Line ; Cholesterol, LDL/metabolism ; Colorectal Neoplasms/chemically induced/metabolism/*pathology ; Disease Models, Animal ; Humans ; Inflammation ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Oxidative Stress ; Precancerous Conditions ; Pyruvaldehyde/*administration &amp; dosage ; Transplantation, Isogeneic ; }, abstract = {Methylglyoxal (MG), a highly reactive carbonyl species (RCS) with pro-oxidant and proinflammatory properties, may be a colon tumor-promoting factor in food and biological systems. In the present study, we found that consumption of MG significantly deteriorated azoxymethane (AOM)-induced colonic preneoplastic lesions in ICR mice, in which biomarkers of oxidative stress and inflammation within the body and feces induced by MG-fueled carbonyl stress may have played important roles. Interestingly, exposure to MG also led to increases in the serum low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio and fecal bile acid levels in mice, which may be critical factors involved in MG-induced colonic lesions. Additionally, MG treatment (50mg/kg body weight (BW); intraperitoneally) promoted tumor growth of CT26 isografts in mice partly by carbonyl stress-evoked protumorigenic responses, including low-grade inflammation and oxidative stress. Furthermore, primary tumor cells isolated from mice with MG-induced CT26 isografts had greater proliferative and migratory activities as well as stem-like properties compared to those isolated from the vehicle controls. Excitingly, enhanced expression or activation of proteins that modulate cell survival, proliferation, or migration/invasion was also observed in those cells. In conclusion, it is conceivable that MG-induced carbonyl stress may be the pivotal promoter involved in colon cancer progression.}, }
@article {pmid29268595, year = {2018}, author = {Cassard, AM and Ciocan, D}, title = {Microbiota, a key player in alcoholic liver disease.}, journal = {Clinical and molecular hepatology}, volume = {24}, number = {2}, pages = {100-107}, pmid = {29268595}, issn = {2287-285X}, mesh = {Animals ; Bacteria/isolation &amp; purification ; Dietary Fiber/therapeutic use ; Fecal Microbiota Transplantation ; Fungi/isolation &amp; purification/physiology ; *Gastrointestinal Microbiome ; Humans ; Liver Diseases, Alcoholic/diet therapy/*pathology/therapy ; Probiotics/therapeutic use ; Severity of Illness Index ; }, abstract = {Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. Only 20% of heavy alcohol consumers develop alcoholic liver cirrhosis. The intestinal microbiota (IM) has been recently identified as a key player in the severity of liver injury in ALD. Common features of ALD include a decrease of gut epithelial tight junction protein expression, mucin production, and antimicrobial peptide levels. This disruption of the gut barrier, which is a prerequisite for ALD, leads to the passage of bacterial products into the blood stream (endotoxemia). Moreover, metabolites produced by bacteria, such as short chain fatty acids, volatile organic compounds (VOS), and bile acids (BA), are involved in ALD pathology. Probiotic treatment, IM transplantation, or the consumption of dietary fiber, such as pectin, which all alter the ratio of bacterial species, have been shown to improve liver injury in animal models of ALD and to be associated with an improvement in gut barrier function. Although the connections between the microbiota and the host in ALD are well established, the underlying mechanisms are still an active area of research. Targeting the microbiome through the use of prebiotic, probiotic, and postbiotic modalities could be an attractive new approach to manage ALD.}, }
@article {pmid29267377, year = {2017}, author = {Paul, B and Royston, KJ and Li, Y and Stoll, ML and Skibola, CF and Wilson, LS and Barnes, S and Morrow, CD and Tollefsbol, TO}, title = {Impact of genistein on the gut microbiome of humanized mice and its role in breast tumor inhibition.}, journal = {PloS one}, volume = {12}, number = {12}, pages = {e0189756}, pmid = {29267377}, issn = {1932-6203}, support = {R01 CA2044346/NH/NIH HHS/United States ; R01 CA178441/NH/NIH HHS/United States ; K01 AT009373/AT/NCCIH NIH HHS/United States ; P30 DK079337/DK/NIDDK NIH HHS/United States ; R03 CA176766/CA/NCI NIH HHS/United States ; R01 CA204446/CA/NCI NIH HHS/United States ; R01 CA204346/CA/NCI NIH HHS/United States ; P30 CA013148/CA/NCI NIH HHS/United States ; R01 CA178441/CA/NCI NIH HHS/United States ; P30 DK056336/DK/NIDDK NIH HHS/United States ; P30 AR050948/AR/NIAMS NIH HHS/United States ; S10 RR027822/RR/NCRR NIH HHS/United States ; UL1 TR001417/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Anticarcinogenic Agents/*pharmacology ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy/*prevention &amp; control ; *Disease Models, Animal ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Genistein/*pharmacology ; Humans ; Mice ; Middle Aged ; }, abstract = {Since dietary polyphenols can have beneficial effects in prevention and treatment of cancer, we tested the hypothesis that breast cancer patients' intestinal microbiota is modulated by genistein (GE), an isoflavone found in soy, and that microbial alterations may offset the side effects brought about by chemotherapy. We demonstrated successful humanization of germ-free mice by transplanting fecal samples from breast cancer patients before and after chemotherapy. Mice were then grouped based on chemotherapy status and GE or control diet. We did not find any significant differences between pre-chemotherapy and post-chemotherapy bacterial composition and abundances. Germ-free mice on a GE diet showed differences in microbial composition as compared to mice on control diet. Four weeks after introduction of the customized GE diet, there was distinct clustering of GE-fed mice as compared to the control-fed group. In the gut microbiome of GE-treated humanized mice, there was an increase in abundance of genera Lactococcus and Eubacterium. Phylum Verrucomicrobia showed statistically significant (p = 0.02) differences in abundances between the GE-fed and control-fed groups. There was an increase in bacteria belonging to family Lachnospiraceae and Ruminococcaceae in GE-fed mice. Marked changes were observed in GE catabolism in mice humanized with fecal material from two of three patients' post-chemotherapy with complete disappearance of 4-ethylphenol and 2-(4-hydroxyphenol) propionic acid conjugates. The post-tumor samples did not show any distinct clustering of the gut microbiota between the two diet groups. There was an increase in latency of about 25% for tumor growth of the humanized mice that were on a GE diet as compared to humanized mice on a control diet. The average tumor size for the GE group was significantly decreased compared to the non-GE group. Collectively, our results suggest that the intestinal microbiota becomes altered with a GE diet before induction of tumor. Our findings indicate that GE modulates the microbiome in humanized mice that may contribute to its effects on increasing the latency of breast tumor and reducing tumor growth.}, }
@article {pmid29261736, year = {2017}, author = {Camacho-Ortiz, A and Gutiérrez-Delgado, EM and Garcia-Mazcorro, JF and Mendoza-Olazarán, S and Martínez-Meléndez, A and Palau-Davila, L and Baines, SD and Maldonado-Garza, H and Garza-González, E}, title = {Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome.}, journal = {PloS one}, volume = {12}, number = {12}, pages = {e0189768}, pmid = {29261736}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteria/genetics ; Biodiversity ; Clostridium Infections/drug therapy/*therapy ; Demography ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Genotype ; Humans ; Male ; Metagenomics ; Microbial Sensitivity Tests ; Middle Aged ; Phylogeny ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics ; Species Specificity ; Tissue Donors ; Vancomycin/therapeutic use ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome.<br><br>METHODS: We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10-14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario "Dr. Jose Eleuterio Gonzalez". Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50% in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria). From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing.<br><br>RESULTS: We included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9%) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1%) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4%) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients. Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably stable over time. The vancomycin group showed a very different pattern of the microbial composition when comparing to the FMT-FURM group over time.<br><br>CONCLUSION: The results of this preliminary study showed that FMT-FURM for initial CDI is associated with specific bacterial communities that do not resemble the donors' sample.}, }
@article {pmid29257783, year = {2018}, author = {Akrami, K and Sweeney, DA}, title = {The microbiome of the critically ill patient.}, journal = {Current opinion in critical care}, volume = {24}, number = {1}, pages = {49-54}, doi = {10.1097/MCC.0000000000000469}, pmid = {29257783}, issn = {1531-7072}, mesh = {Clostridium Infections/microbiology/therapy ; Colitis, Ulcerative/microbiology/therapy ; *Critical Illness/therapy ; Dysbiosis/etiology/*microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; Intensive Care Units ; Microbiota/*physiology ; Pneumonia, Ventilator-Associated/microbiology/therapy ; Probiotics/therapeutic use ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Advances in the understanding of the human microbiome outside of the ICU have led investigators to consider the role of the microbiome in critical illness. The picture that is being elucidated is one of dysbiosis occurring at multiple sites in the critically ill patient. This review describes the changes that occur in the various microbiomes of a critically ill patient, the implications of these changes and shows how advances in the understanding of dysbiosis may lead to microbiome-targeted therapies.<br><br>RECENT FINDINGS: Critically ill patients undergo dysbiosis at several organ sites including the skin, gastrointestinal system and the lungs with loss of microbial diversity and a propensity for potentially pathogenic organisms to dominate a particular microbiome. These microbiome changes appear to be predictive of clinical outcome. While the use of fecal microbial transplantation has been demonstrated to be an effective treatment for recurrent Clostridium difficile infection, the use of fecal microbial transplantation and other microbiome modifying therapies may have a role in managing critical illness in the ICU.<br><br>SUMMARY: A growing understanding of the microbiome in the critically ill may modify current dogma regarding the pathogenesis of sepsis and other life-threatening conditions seen in the ICU, thereby fundamentally changing antibiotic stewardship and the management of the critically ill patient.}, }
@article {pmid29256139, year = {2018}, author = {Turner, JS and Okonkwo, A and Chase, A and Clark, CE}, title = {Early outcomes of fluorescence angiography in the setting of endorectal mucosa advancement flaps.}, journal = {Techniques in coloproctology}, volume = {22}, number = {1}, pages = {25-30}, pmid = {29256139}, issn = {1128-045X}, mesh = {Adult ; Female ; Fluorescein Angiography/*methods ; Humans ; Intestinal Mucosa/*diagnostic imaging/transplantation ; Intraoperative Care/*methods ; Male ; Middle Aged ; Prospective Studies ; Rectal Fistula/*diagnostic imaging/surgery ; Rectum/diagnostic imaging/surgery ; Recurrence ; *Surgical Flaps ; Treatment Outcome ; }, abstract = {BACKGROUND: Fistula-in-ano has a reported incidence of 31-34%. Besides fistulotomy, options for fistula repair are seton placement, endorectal advancement flap (ERAF), fibrin sealant, anal fistula plug and ligation of the intersphincteric fistula tract. Despite having a reported success rate as high as 75-98%, ERAF is not without complications, including flap breakdown, recurrence and fecal incontinence. Traditionally, maintaining a broad base to preserve blood supply has been advocated to reduce flap failure. And the aim of the present study was to evaluate outcomes of adult patients who underwent ERAF for complex fistula-in-ano with the use of intraoperative fluorescence angiography (FA) at our institution between July 2014 and July 2016.<br><br>METHODS: We retrospectively reviewed consecutive cases of complex fistula-in-ano repair with ERAF and FA from a prospectively maintained dataset of adult patients with complex fistula-in-ano. Demographics, intraoperative data and 60-day outcomes were recorded and reviewed.<br><br>RESULTS: Six patients [five males and one female with a mean age of 40&#xa0;years (range 25-46&#xa0;years)], with a total of seven fistulas, were identified. Six (85.7%) of these patients had undergone prior surgery for fistula-in-ano. No recurrences or complications of any type were noted at 2-week and 8-week follow-up. The majority of patients (71.4%) required flap revision based on intraoperative FA prior to flap fixation.<br><br>CONCLUSIONS: FA is safe and offers real-time assessment of flap perfusion prior to and after fixation in anal fistula repair. The rate of flap ischemia may be underestimated, and therefore, to improve outcomes in ERAF, intraoperative FA should be included in the surgical armamentarium.}, }
@article {pmid29256106, year = {2018}, author = {Pomian, A and Majkusiak, W and Lisik, W and Tomasik, P and Horosz, E and Zwierzchowska, A and Kociszewski, J and Barcz, E}, title = {Is Bariatric Surgery a Prophylaxis for Pelvic Floor Disorders?.}, journal = {Obesity surgery}, volume = {28}, number = {6}, pages = {1653-1658}, pmid = {29256106}, issn = {1708-0428}, mesh = {*Bariatric Surgery ; Case-Control Studies ; Humans ; Obesity, Morbid/*surgery ; *Pelvic Floor Disorders/diagnostic imaging/epidemiology/prevention &amp; control ; Prospective Studies ; Ultrasonography ; }, abstract = {INTRODUCTION: Obesity is one of the well-documented risk factors of pelvic floor disorders (PFDs). The PFDs include urinary and fecal incontinence (UI, FI) and pelvic organ prolapse (POP). Surgery-induced weight loss improves different kinds of incontinence as well as POP symptoms. However, there is a lack of evidence how bariatric surgery influences pelvic floor anatomy and function in women without previous PFDs and whether it may be concerned as PFD prophylaxis tool.<br><br>MATERIALS AND METHODS: The present analysis is a prospective, non-randomized case-control study from January 2014 to September 2017. Participants underwent pelvic floor ultrasound examination with bladder neck position estimation at rest, during levator ani tension, and at Valsalva maneuver before surgery and 12-18&#xa0;months after. Pelvic organ prolapse quantification (POPQ) >&#x2009;2 stage and PFD complaints were the exclusion criteria.<br><br>RESULTS: Fifty-nine patients underwent bariatric surgery (57 sleeve gastrectomy and 2 gastric bypass). Mean BMI decreased from 43.8&#x2009;&#xb1;&#x2009;5.9 to 29&#x2009;&#xb1;&#x2009;4.6&#xa0;kg/m[2] after surgery (p&#x2009;<&#x2009;0.001). Statistically significant higher position of the bladder neck at rest, during tension, and at Valsalva maneuver (p&#x2009;<&#x2009;0.05) was shown after surgery. We did not demonstrate differences in bladder neck mobility and bladder neck elevation at tension after weight loss.<br><br>CONCLUSIONS: Bariatric surgery is associated with a betterment of bladder neck position at rest, tension, and Valsalva maneuver in women without PFDs. We postulate that bariatric surgery may be a tool for PFD prevention. It does not improve levator ani function and does not limit bladder neck mobility, which implicates that it has no influence on preexisting pelvic dysfunction.}, }
@article {pmid29255739, year = {2017}, author = {Craven, LJ and Nair Parvathy, S and Tat-Ko, J and Burton, JP and Silverman, MS}, title = {Extended Screening Costs Associated With Selecting Donors for Fecal Microbiota Transplantation for Treatment of Metabolic Syndrome-Associated Diseases.}, journal = {Open forum infectious diseases}, volume = {4}, number = {4}, pages = {ofx243}, pmid = {29255739}, issn = {2328-8957}, abstract = {BACKGROUND: Knowledge of the impact of the gut microbiome on conditions other than Clostridium difficile infection has been rapidly increasing, and the potential usefulness of fecal microbiota transplantation (FMT) in these indications is being explored. The need to exclude donors with an increased risk of these diseases has left uncertainties regarding the cost and feasibility of donor screening. The aim of this study was to compare our experience to other donor-screening programs and report the costs associated with establishing a donor-screening program, for the treatment of metabolic syndrome-related conditions.<br><br>METHODS: Forty-six potential donors (PDs) had their medical histories and physical examinations undertaken by a physician. Blood, stool, and urine were screened for 31 viral, bacterial, fungal, and protozoan agents in addition to biochemical characteristics. The price of advertising, doctor's visits and diagnostic tests were calculated to determine the cost of finding a donor.<br><br>RESULTS: Of the PDs screened, 5 of 46 passed the history, examination, blood, stool, and urine tests. The most common reasons for exclusion included a body mass index >25 or the detection of Blastocystis hominis, Dientamoeba fragilis, or Helicobacter pylori. Four of five eligible donors had subsequent travel or illness that contraindicated donation, so only 1 of 46 PDs was suitable. The total cost for finding a single suitable donor was $15190 US dollars. This screening was performed in Canada, and costs in the United States would be substantially higher.<br><br>CONCLUSIONS: New potential therapeutic uses for FMT have created a demand for stricter exclusion criteria for donors. This study illustrates that screening many individuals to find a donor and the subsequent associated costs may make central processing and shipment a more reasonable alternative.}, }
@article {pmid29246701, year = {2018}, author = {Fischer, M and Kao, D and Kassam, Z and Smith, J and Louie, T and Sipe, B and Torbeck, M and Xu, H and Ouyang, F and Mozaffarian, D and Allegretti, JR}, title = {Stool Donor Body Mass Index Does Not Affect Recipient Weight After a Single Fecal Microbiota Transplantation for Clostridium difficile Infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {16}, number = {8}, pages = {1351-1353}, doi = {10.1016/j.cgh.2017.12.007}, pmid = {29246701}, issn = {1542-7714}, mesh = {Adult ; Aged ; Body Mass Index ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*adverse effects ; Female ; Humans ; Male ; Middle Aged ; Obesity/*epidemiology ; Tissue Donors ; *Transplant Recipients ; }, }
@article {pmid29244178, year = {2017}, author = {Tran, J and Wilson, K and Plebanski, M and Flanagan, KL}, title = {Manipulating the microbiota to improve human health throughout life.}, journal = {Transactions of the Royal Society of Tropical Medicine and Hygiene}, volume = {111}, number = {9}, pages = {379-381}, doi = {10.1093/trstmh/trx068}, pmid = {29244178}, issn = {1878-3503}, mesh = {*Health Promotion ; *Health Status ; Humans ; Immunity/*physiology ; *Microbiota ; Nutritional Status ; Prebiotics/administration &amp; dosage ; }, }
@article {pmid29243124, year = {2018}, author = {Gorkiewicz, G and Moschen, A}, title = {Gut microbiome: a new player in gastrointestinal disease.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {472}, number = {1}, pages = {159-172}, pmid = {29243124}, issn = {1432-2307}, support = {FWF W1241-B18//FWF/ ; }, mesh = {Gastrointestinal Diseases/*microbiology ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {The gastrointestinal (GI) tract harbors a diverse and host-specific gut microbial community. Whereas host-microbe interactions are based on homeostasis and mutualism, the microbiome also contributes to disease development. In this review, we summarize recent findings connecting the GI microbiome with GI disease. Starting with a description of biochemical factors shaping microbial compositions in each gut segment along the longitudinal axis, improved histological techniques enabling high resolution visualization of the spatial microbiome structure are highlighted. Subsequently, inflammatory and neoplastic diseases of the esophagus, stomach, and small and large intestines are discussed and the respective changes in microbiome compositions summarized. Finally, approaches aiming to restore disturbed microbiome compositions thereby promoting health are discussed.}, }
@article {pmid29242336, year = {2017}, author = {Hoffmann, D and Palumbo, F and Ravel, J and Roghmann, MC and Rowthorn, V and von Rosenvinge, E}, title = {Improving regulation of microbiota transplants.}, journal = {Science (New York, N.Y.)}, volume = {358}, number = {6369}, pages = {1390-1391}, pmid = {29242336}, issn = {1095-9203}, support = {R21 AI119633/AI/NIAID NIH HHS/United States ; }, mesh = {Biological Specimen Banks ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*standards ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Policy ; Safety ; }, }
@article {pmid29241627, year = {2018}, author = {Sierra Salinas, C and Vicioso Recio, MI and Blasco-Alonso, J and Serrano Nieto, MJ and Navas-López, VM}, title = {[Faecal microbiota transplant in a child with very early onset inflammatory bowel disease].}, journal = {Anales de pediatria}, volume = {89}, number = {3}, pages = {184-186}, doi = {10.1016/j.anpedi.2017.10.011}, pmid = {29241627}, issn = {2341-2879}, mesh = {Age Factors ; Child ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*therapy ; Male ; }, }
@article {pmid29239198, year = {2019}, author = {Vigvári, S and Sipos, D and Solt, J and Vincze, &#xc1; and Kocsis, B and Nemes, Z and Kappéter, &#xc1; and Feiszt, Z and Kovács, B and Péterfi, Z}, title = {Faecal microbiota transplantation for Clostridium difficile infection using a lyophilized inoculum from non-related donors: A case series involving 19 patients.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {66}, number = {1}, pages = {69-78}, doi = {10.1556/030.64.2017.042}, pmid = {29239198}, issn = {1588-2640}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; Diarrhea/therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; *Freeze Drying ; Humans ; Male ; Middle Aged ; *Tissue Donors ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) has been reported to be effective in treating relapsing of refractory Clostridium difficile infections, although some practical barriers are limiting its widespread use. In this study, our objective was to evaluate the rate of resolution of diarrhea following administration of lyophilized and resolved FMT via a nasogastric (NG) tube. We recruited 19 patients suffered from laboratory-confirmed C. difficile infection. Each of them was treated by lyophilized and resolved inoculum through a NG tube. One participant succumbed following the procedure due to unrelated diseases. Out of 18 cases, 15 patients reportedly experienced a resolution of the symptoms. One patient was treated with another course of antibiotics, and two of the non-responders were successfully retreated with another course of FMT utilizing a lyophilized inoculum. Notably, no significant adverse activities were observed. In accordance to our clinical experiences, a patient will likely benefit from FMT treatment including lyophilized inoculum.}, }
@article {pmid29233031, year = {2018}, author = {Varkey, J and Stotzer, PO and Simrén, M and Herlenius, G and Oltean, M}, title = {The endoscopic surveillance of the transplanted small intestine: a single center experience and a proposal for a grading score.}, journal = {Scandinavian journal of gastroenterology}, volume = {53}, number = {2}, pages = {134-139}, doi = {10.1080/00365521.2017.1411523}, pmid = {29233031}, issn = {1502-7708}, mesh = {Adolescent ; Adult ; Aged ; Biopsy ; Child ; Child, Preschool ; *Endoscopy, Gastrointestinal ; Feces/chemistry ; Female ; Graft Rejection/*diagnosis/pathology ; Humans ; Intestinal Mucosa/*pathology ; Intestine, Small/*transplantation ; Leukocyte L1 Antigen Complex/analysis ; Male ; Middle Aged ; Monitoring, Physiologic ; Retrospective Studies ; Sensitivity and Specificity ; Sweden ; Young Adult ; }, abstract = {OBJECTIVE: Microscopic examination of endoscopic biopsies forms the basis of acute cellular rejection (ACR) monitoring after intestinal transplantation (ITx). The endoscopy findings during acute rejection (AR) are known but a grading system for its severity is lacking. We designed and implemented a five-stage grading score based on acknowledged endoscopic features of AR, to allow a faster preliminary diagnosis of AR and intra- and interpatient comparisons.<br><br>METHODS: Two investigators reviewed and graded the endoscopy reports after 28 ITx using a novel score and correlated the results with pathology findings.<br><br>RESULTS: We reviewed 512 ileoscopies: 370 examinations (74%) were normal (G0), 59 had mild alterations (erythema, edematous villi-G1) and 36 showed moderate changes (erosions, blunted villi-G2); 17 ileoscopies revealed advanced changes (ulcerations, villus loss-G3). In 18 endoscopies the changes were severe (mucosal loss-G4). Inter-reviewer agreement was very good (kappa&#x2009;=&#x2009;0.81). Biopsies from 86 endoscopy sessions (17%) indicated ACR with 63 cases having moderate or severe ACR. For mild ACR the sensitivity of the score was 29% and the specificity was 86% whereas the positive (PPV) and negative predictive values (NPVs) were 14% and 93% respectively. During advanced ACR the sensitivity and specificity were 92% and 86%, respectively whereas the PPV and NPV were 49% and 98% respectively.<br><br>CONCLUSIONS: Endoscopy alone has a limited ability to reliably diagnose intestinal ACR. We suggest a novel grading score summarizing ACR findings and allowing comparisons between intestinal graft endoscopies.}, }
@article {pmid29226561, year = {2018}, author = {Jalanka, J and Hillamaa, A and Satokari, R and Mattila, E and Anttila, VJ and Arkkila, P}, title = {The long-term effects of faecal microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent Clostridium difficile infection.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {47}, number = {3}, pages = {371-379}, doi = {10.1111/apt.14443}, pmid = {29226561}, issn = {1365-2036}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Case-Control Studies ; Clostridioides difficile/physiology ; Clostridium Infections/*epidemiology/*therapy ; Fecal Microbiota Transplantation/*adverse effects/statistics &amp; numerical data ; Female ; Follow-Up Studies ; Humans ; Inflammatory Bowel Diseases/epidemiology/therapy ; Male ; Middle Aged ; Quality of Life ; Retrospective Studies ; Surveys and Questionnaires ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection. In short-term the treatment has been shown to be safe, however, there are no large, long-term follow-up studies looking into the potential adverse effects.<br><br>AIM: To analyse the long-term effect of FMT treatment in patients with recurrent C. difficile infection and to compare the outcome to antibiotic treated patients.<br><br>METHODS: Altogether 84 patients of which 45 received a FMT treatment and 39 served as controls receiving antibiotics for the infection were followed on average for 3.8&#xa0;years. Their recovery and medical status was evaluated using a retrospective questionnaire, determining their quality of life, gastrointestinal symptoms and new diseases potentially related to the FMT.<br><br>RESULTS: There was no difference in the incidence of severe diseases (inflammatory bowel disease, cancer, autoimmune disease, allergy, neurological diseases) between the patient groups. In addition, weight gain did not differ between treatment groups. The FMT treated patients reported that their bowel habits improved significantly faster, they had less irregular bowel function and less symptoms of upper GI-tract when compared to the patients treated with antibiotics. Significantly more patients in FMT-group reported that their mental health improved after the treatment. The willingness to receive FMT treatment for potential new C. difficile infection was significantly higher in both treatment groups compared to other treatment options.<br><br>CONCLUSION: Our study highlights that FMT is a durable, safe and acceptable treatment option for patients with recurrent C. difficile infection also in long term, and it shows potential benefits over antimicrobial treatment.}, }
@article {pmid29217301, year = {2018}, author = {Bruneau, A and Baylatry, MT and Joly, AC and Sokol, H}, title = {[Gut microbiota: What impact on colorectal carcinogenesis and treatment?].}, journal = {Bulletin du cancer}, volume = {105}, number = {1}, pages = {70-80}, doi = {10.1016/j.bulcan.2017.10.025}, pmid = {29217301}, issn = {1769-6917}, mesh = {Bacterial Toxins/metabolism ; Bacteroides fragilis ; Cell Proliferation ; Colorectal Neoplasms/*microbiology/*therapy ; Drug Resistance, Neoplasm ; Dysbiosis/chemically induced/complications ; Enterococcus faecalis ; Escherichia coli ; Faecalibacterium prausnitzii ; Fecal Microbiota Transplantation ; Fusobacterium nucleatum ; *Gastrointestinal Microbiome/physiology ; Humans ; Neovascularization, Pathologic/microbiology ; Probiotics/therapeutic use ; Streptococcus gallolyticus ; }, abstract = {The gut microbiota, composed of 10[14] microorganisms, is now considered as a "hidden organ", regarding to its digestive, metabolic and immune functions, which are helpful to its host. For the last 15 years, advances in molecular biology have highlighted the association of gut microbiota dysbiosis with several diseases, including colorectal cancer. An increased abundance of some bacteria (including Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli) is associated with cancer, whereas others seem to be protective (Faecalibacterium prausnitzii). Several mechanisms, which are species-specific, are involved in colorectal carcinogenesis. Most of the time, bacterial toxins are involved in pro-inflammatory processes and in activation of angiogenesis and cellular proliferation pathways. The identification of these bacteria leads to envisage the gut microbiota as potential screening tool for colorectal cancer. Recent studies showed a relation between the gut microbiota and the efficacy and toxicity of chemotherapies (oxaliplatin, irinotecan) and immunotherapies (including ipilimumab). Therapeutic approaches targeting the gut microbiota are now available (probiotics, fecal microbiota transplantation…). New therapeutic strategy combining both chemotherapy and/or immunotherapy with an adjuvant treatment targeting the gut microbiota can now be developed in order to improve treatment response and tolerance.}, }
@article {pmid29214770, year = {2018}, author = {Yoon, MY and Yoon, SS}, title = {Disruption of the Gut Ecosystem by Antibiotics.}, journal = {Yonsei medical journal}, volume = {59}, number = {1}, pages = {4-12}, pmid = {29214770}, issn = {1976-2437}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/drug effects/growth &amp; development ; Dysbiosis/microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intestines/drug effects/microbiology ; Symbiosis/drug effects ; }, abstract = {The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state.}, }
@article {pmid29212595, year = {2017}, author = {Knudsen, JK and Bundgaard-Nielsen, C and Hagstrøm, S and Sørensen, S and Leutscher, P}, title = {[The human gut microbiota].}, journal = {Ugeskrift for laeger}, volume = {179}, number = {49}, pages = {}, pmid = {29212595}, issn = {1603-6824}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/therapy ; Metabolic Syndrome/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Characterization of the human gut microbiota has caused a paradigm shift in modern biomedical research. Maintenance of gut microbiota depends on mutual microbe-host interactions, which when disturbed can lead to dysbiosis. Dysbiosis has been associated with a variety of autoimmune and metabolic diseases. Studies attempt to define bacterial compositional changes, immunity responses or molecular patterns associated with specific diseases. The immense research in the human microbiota may lead to novel therapeutic strategies by development of commensal microbe products in management of diseases.}, }
@article {pmid29212476, year = {2017}, author = {Fugazza, A and Bizzarri, B and Gaiani, F and Manfredi, M and Ghiselli, A and Crafa, P and Carra, MC and de'Angelis, N and de'Angelis, GL}, title = {The role of endoscopic ultrasound in children with Pancreatobiliary and gastrointestinal disorders: a single center series and review of the literature.}, journal = {BMC pediatrics}, volume = {17}, number = {1}, pages = {203}, pmid = {29212476}, issn = {1471-2431}, mesh = {Adolescent ; Child ; Child, Preschool ; Databases, Factual ; *Endosonography ; Feasibility Studies ; Female ; Follow-Up Studies ; Gallstones/*diagnostic imaging ; Gastrointestinal Diseases/*diagnostic imaging ; Humans ; Male ; Pancreatic Cyst/*diagnostic imaging ; Pancreatitis/*diagnostic imaging ; Retrospective Studies ; }, abstract = {BACKGROUND: The role of endoscopic ultrasound (EUS) in the management of pancreatobiliary and digestive diseases is well established in adults, but it remains limited in children. The aim of this study was to evaluate the feasibility, safety, and clinical impact of EUS use in children.<br><br>METHODS: This is a retrospective analysis of a prospectively acquired database of consecutive pediatric (< 18&#xa0;years) patients presenting an indication for EUS for pancreatobiliary and gastrointestinal disorders.<br><br>RESULTS: Between January 2010 and January 2016, 47 procedures were performed in 40 children (mean age of 15.1&#x2009;&#xb1;&#x2009;4.7&#xa0;years; range 3-18). The majority of EUS (n&#x2009;=&#x2009;32; 68.1%) were performed for pancreatobiliary and upper gastrointestinal pathologies, including suspected common bile duct stones (CBDs), acute biliary pancreatitis, recurrent/chronic pancreatitis, cystic pancreatic mass, recurrent hypoglycemia, duodenal polyp, gastric submucosal lesion, and perigastric abscess. In only 2 out of 18 children with suspected CBDs or acute biliary pancreatitis, EUS confirmed CBDs. EUS-guided fine needle aspiration was performed in 3 (6.4%) patients. Fifteen (31.9%) procedures were performed for lower gastrointestinal tract disorders, including suspected anal Crohn's disease, fecal incontinence, and encopresis. Overall, EUS had a significant impact on the subsequent clinical management in 87.2% of patients.<br><br>CONCLUSION: The present findings were consistent with results observed in the current relevant literature and support EUS as a safe and feasible diagnostic and therapeutic tool, which yields a significant clinical impact in children with pancreatobiliary and gastrointestinal disorders.}, }
@article {pmid29211757, year = {2017}, author = {de Groot, PF and Belzer, C and Aydin, &#xd6; and Levin, E and Levels, JH and Aalvink, S and Boot, F and Holleman, F and van Raalte, DH and Scheithauer, TP and Simsek, S and Schaap, FG and Olde Damink, SWM and Roep, BO and Hoekstra, JB and de Vos, WM and Nieuwdorp, M}, title = {Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study.}, journal = {PloS one}, volume = {12}, number = {12}, pages = {e0188475}, pmid = {29211757}, issn = {1932-6203}, mesh = {Diabetes Mellitus, Type 1/*microbiology ; Feces/*microbiology ; Humans ; *Microbiota ; Mouth/*microbiology ; }, abstract = {OBJECTIVE: Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking.<br><br>RESEARCH DESIGN AND METHODS: We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured.<br><br>RESULTS: Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA.<br><br>CONCLUSIONS: We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.}, }
@article {pmid29209564, year = {2017}, author = {Jala, VR and Maturu, P and Bodduluri, SR and Krishnan, E and Mathis, S and Subbarao, K and Wang, M and Jenson, AB and Proctor, ML and Rouchka, EC and Knight, R and Haribabu, B}, title = {Leukotriene B4-receptor-1 mediated host response shapes gut microbiota and controls colon tumor progression.}, journal = {Oncoimmunology}, volume = {6}, number = {12}, pages = {e1361593}, pmid = {29209564}, issn = {2162-4011}, support = {P20 GM103436/GM/NIGMS NIH HHS/United States ; R01 CA138623/CA/NCI NIH HHS/United States ; }, abstract = {Inflammation and infection are key promoters of colon cancer but the molecular interplay between these events is largely unknown. Mice deficient in leukotriene B4 receptor1 (BLT1) are protected in inflammatory disease models of arthritis, asthma and atherosclerosis. In this study, we show that BLT1[-/-] mice when bred onto a spontaneous tumor (Apc[Min/+]) model displayed an increase in the rate of intestinal tumor development and mortality. A paradoxical increase in inflammation in the tumors from the BLT1[-][/][-]Apc[Min/+] mice is coincidental with defective host response to infection. Germ-free BLT1[-][/][-]Apc[Min/+] mice are free from colon tumors that reappeared upon fecal transplantation. Analysis of microbiota showed defective host response in BLT1[-/-] Apc[Min/+] mice reshapes the gut microbiota to promote colon tumor development. The BLT1[-/-]MyD88[-/-] double deficient mice are susceptible to lethal neonatal infections. Broad-spectrum antibiotic treatment eliminated neonatal lethality in BLT1[-/-]MyD88[-/-] mice and the BLT1[-/-]MyD88[-/-]Apc[Min+] mice are protected from colon tumor development. These results identify a novel interplay between the Toll-like receptor mediated microbial sensing mechanisms and BLT1-mediated host response in the control of colon tumor development.}, }
@article {pmid29209047, year = {2018}, author = {Atreya, R and Siegmund, B}, title = {IBD in 2017: Development of therapy for and prediction of IBD - getting personal.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {15}, number = {2}, pages = {72-74}, pmid = {29209047}, issn = {1759-5053}, mesh = {*Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases ; }, }
@article {pmid29208562, year = {2018}, author = {Chilton, CH and Pickering, DS and Freeman, J}, title = {Microbiologic factors affecting Clostridium difficile recurrence.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {24}, number = {5}, pages = {476-482}, doi = {10.1016/j.cmi.2017.11.017}, pmid = {29208562}, issn = {1469-0691}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; *Clostridioides difficile/classification/genetics ; Clostridium Infections/diagnosis/*microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Humans ; Microbial Viability/drug effects ; Recurrence ; Risk Factors ; Spores, Bacterial/drug effects ; Superinfection ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (rCDI) places a huge economic and practical burden on healthcare facilities. Furthermore, rCDI may affect quality of life, leaving patients in an rCDI cycle and dependant on antibiotic therapy.<br><br>AIMS: To discuss the importance of microbiologic factors in the development of rCDI.<br><br>SOURCES: Literature was drawn from a search of PubMed from 2000 onwards with the search term 'recurrent Clostridium difficile infection' and further references cited within these articles.<br><br>CONTENT: Meta-analyses and systematic reviews have shown that CDI and rCDI risk factors are similar. Development of rCDI is attendant on many factors, including immune status or function, comorbidities and concomitant treatments. Studies suggest that poor bacterial diversity is correlated with clinical rCDI. Narrow-spectrum gut microflora-sparing antimicrobials (e.g. surotomycin, cadazolid, ridinilazole) are in development for CDI treatment, while microbiota therapeutics (faecal microbiota transplantation, nontoxigenic C.&#xa0;difficile, stool substitutes) are increasingly being explored. rCDI can only occur when viable C.&#xa0;difficile spores are present, either within the gut lumen after infection or when reacquired from the environment. C.&#xa0;difficile spore germination can be influenced by gut environmental factors resulting from dysbiosis, and spore outgrowth may be affected stage by some antimicrobials (e.g. fidaxomicin, ramoplanin, oritavancin).<br><br>IMPLICATIONS: rCDI is a significant challenge for healthcare professionals, requiring a multifaceted approach; optimized infection control to minimize reinfection; C.&#xa0;difficile-targeted antibiotics to minimize dysbiosis; and gut microflora restoration to promote colonization resistance. These elements should be informed by our understanding of the microbiologic factors involved in both C.&#xa0;difficile itself and the gut microbiome.}, }
@article {pmid29205849, year = {2018}, author = {Kreft, JU}, title = {Editorial: The microbiome as a source of new enterprises and job creation.}, journal = {Microbial biotechnology}, volume = {11}, number = {1}, pages = {145-148}, pmid = {29205849}, issn = {1751-7915}, support = {NC/K000683/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; NC/R001707/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; }, mesh = {Biomedical Research/*trends ; Dysbiosis/*prevention &amp; control/*therapy ; Fecal Microbiota Transplantation/methods ; *Microbiota ; Probiotics/administration &amp; dosage ; }, }
@article {pmid29204952, year = {2017}, author = {Konturek, PC and Zopf, Y}, title = {[Therapeutic modulation of intestinal microbiota in irritable bowel syndrome. From probiotics to fecal microbiota therapy].}, journal = {MMW Fortschritte der Medizin}, volume = {159}, number = {Suppl 7}, pages = {1-5}, doi = {10.1007/s15006-017-0338-3}, pmid = {29204952}, issn = {1613-3560}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Humans ; Irritable Bowel Syndrome/therapy ; Probiotics/*therapeutic use ; }, abstract = {BACKGROUND: An abnormal intestinal microbiota (dysbiosis) plays a central role in the pathogenesis of the irritable bowel syndrome.<br><br>METHOD: An overview of four current options for the treatment of irritable bowel syndrome, which are characterized by modulation of intestinal microbiota, is given.<br><br>RESULTS AND CONCLUSIONS: Probiotics have very different effects on the individual symptoms of the irritable bowel. The choice of the appropriate preparation should therefore be based on the clinical symptomatology. The antibiotic rifaximin is effective in selected patients. Some patients also benefit from the repetition of this therapy. A FODMAP-reduced diet has shown significant alleviation of irritable bowel symptoms in studies. The fecal microbiota therapy (FMT) is a promising treatment option. At present, however, there are no such placebo-controlled studies to assess the effectiveness of this method.}, }
@article {pmid29198923, year = {2017}, author = {Ren, X and Liu, L and Gamallat, Y and Zhang, B and Xin, Y}, title = {Enteromorpha and polysaccharides from enteromorpha ameliorate loperamide-induced constipation in mice.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {96}, number = {}, pages = {1075-1081}, doi = {10.1016/j.biopha.2017.11.119}, pmid = {29198923}, issn = {1950-6007}, mesh = {Animals ; Antidiarrheals/toxicity ; Constipation/*chemically induced/*drug therapy/metabolism ; Female ; Gastrointestinal Transit/drug effects/physiology ; Laxatives/isolation &amp; purification/pharmacology/therapeutic use ; Loperamide/*toxicity ; Mice ; Plant Extracts/isolation &amp; purification/pharmacology/*therapeutic use ; Polysaccharides/isolation &amp; purification/pharmacology/*therapeutic use ; *Ulva ; }, abstract = {Slow-transit constipation(STC)is a disease characterized by functional gastrointestinal disorder. Common laxatives used in clinical practice against constipation such as Senna have side effects. Enteromorpha(EP)is a common marine alga, and the polysaccharide extracted from EP has been reported possessing anti-cancer and anti-inflammation effects. The aim of this study is to investigate the effects of EP and Polysaccharides from Enteromorpha (PEP) on loperamide induced constipated mice model and illustrating mechanism of action. We investigated the effect of EP and PEP on fecal water content, defecation frequency and gastrointestinal transit (GI) time of loperamide-induced STC mice. In addition, serum Nitric Oxide (NO) content and vasoactive intestinal peptide receptor1 (VIPR1) as well as serotonin receptor (5-HT4) expression in the distal colon were analyzed. Furthermore, we determined the role of EP and PEP on microbiota distribution using stool genomic 16S rRNA sequencing. EP and PEP significantly enhanced intestinal motility function, and alleviated constipation associated intestinal inflammation. Moreover, EP and PEP significantly decreased serum NO concentration, down-regulated VIPR1 expression and up-regulated 5-HT4 expression in distal colon. Genomic stool DNA MiSeq Sequencing Analysis of microbiota community structures and distribution revealed that intestinal microecological changes caused by constipation recovered after both EP and PEP treatment. Our results indicate that EP and PEP are potent natural products which could be suggested in constipation therapy strategies.}, }
@article {pmid29198534, year = {2018}, author = {Brumbaugh, DE and De Zoeten, EF and Pyo-Twist, A and Fidanza, S and Hughes, S and Dolan, SA and Child, J and Dominguez, SR}, title = {An Intragastric Fecal Microbiota Transplantation Program for Treatment of Recurrent Clostridium difficile in Children is Efficacious, Safe, and Inexpensive.}, journal = {The Journal of pediatrics}, volume = {194}, number = {}, pages = {123-127.e1}, doi = {10.1016/j.jpeds.2017.10.016}, pmid = {29198534}, issn = {1097-6833}, mesh = {Adolescent ; Child ; Child, Preschool ; Clostridioides difficile ; Clostridium Infections/*therapy ; Cohort Studies ; Colonoscopy/methods ; Diarrhea/etiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; Gastrostomy/methods ; Humans ; Infant ; Intubation, Gastrointestinal/methods ; Male ; Recurrence ; Retrospective Studies ; Stomach ; Treatment Outcome ; }, abstract = {OBJECTIVE: To assess the safety, efficacy, and relative expense of a nurse-led fecal microbiota transplantation (FMT) program for the treatment of recurrent Clostridium difficile infection (CDI).<br><br>STUDY DESIGN: Retrospective cohort study design in children aged 1-18 years with recurrent CDI. The intervention was an intragastric FMT with stool derived from a donor stool bank. Primary outcome was resolution of diarrhea at 3 months post-transplantation. A secondary analysis compared charge data associated with FMT by intragastric delivery vs administration by colonoscopy or nasoduodenal tube.<br><br>RESULTS: A total of 47 intragastric FMT procedures were performed in 42 children (median age 9 years) with recurrent CDI. Response to treatment varied by disease status, with 94% success in previously healthy children, 75% in medically complex children, and 54% in children with inflammatory bowel disease (P&#x2009;=&#x2009;.04). FMT via intragastric delivery showed lower facility and professional charges by 85% and 78% compared with delivery via colonoscopy and radiology-placed nasoduodenal tube, respectively. The use of stool derived from a donor stool bank decreased charges by 49% compared with charges associated with the use of a donor who was a relative.<br><br>CONCLUSION: A nurse-led intragastric FMT procedure using stool derived from a donor stool bank is a relatively inexpensive and efficacious treatment for recurrent CDI in children. Intragastric FMT success in children was attenuated by the presence of underlying disease, particularly inflammatory bowel disease.}, }
@article {pmid29193949, year = {2017}, author = {Pérez-Topete, SE and Miranda-Aquino, T and Ayala-Gaytan, JJ}, title = {[Case series of Clostridium difficile NAP1/027/BI with novels treatments].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {55}, number = {5}, pages = {654-659}, pmid = {29193949}, issn = {2448-5667}, mesh = {Aged ; Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*classification/isolation &amp; purification ; Clostridium Infections/diagnosis/microbiology/*therapy ; Drug Therapy, Combination ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Minocycline/*analogs &amp; derivatives/therapeutic use ; Naphthalenes ; Oligopeptides ; Ribotyping ; Tigecycline ; Vancomycin/*therapeutic use ; }, abstract = {BACKGROUND: Clostridium difficile is a spore-forming bacterium, producing exotoxins, causing potentially fatal nosocomial diarrhea. They have recently reported outbreaks of C. difficile ribotype 027, which is characterized by a hypervirulent strain and high resistance to standard therapy.<br><br>CLINICAL CASE: We present three cases of Clostridium difficile NAP1/027/BI associated infection, they were presented with different clinical manifestations. Two of the patients were successfully treated with the combination of vancomycin plus tigecycline. The other case was treated with fecal microbiota transplant, with resolution of the disease.<br><br>CONCLUSION: in patients with Clostridium difficile NAP1/027/BI associated infection is a good therapeutic option to consider the use of tigecycline in conjunction with vancomycin, as well as fecal microbiota transplantation.}, }
@article {pmid29190854, year = {2018}, author = {Kaffarnik, M and Isner, C and Hamsen, U}, title = {[Clostridium difficile Infection: Epidemiology, Clinical Presentation, Therapy and Prevention].}, journal = {Zentralblatt fur Chirurgie}, volume = {143}, number = {3}, pages = {241-249}, doi = {10.1055/s-0043-119894}, pmid = {29190854}, issn = {1438-9592}, mesh = {Aged ; Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship ; *Clostridium Infections/diagnosis/epidemiology/prevention &amp; control/therapy ; Humans ; Middle Aged ; Risk Factors ; }, abstract = {Clostridium difficile infections (CDI) are common causes of diarrhoea in hospitalised medical and surgical patients. Clinical presentation ranges from mild diarrhoea to pseudomembraneous enterocolitis of the colon and sometimes the small intestines, with development of a toxic megacolon. Recurrent infections are common. Early diagnosis is necessary because of high rates of complications and mortality. Knowledge of risk factors for the development of CDI is recommended. Early initiation of therapy is recommended to avoid complications and standard therapy is antibiotics, while therapy with monoclonal antibodies and vaccination is under research and development. Fulminant septic courses indicate surgical source control. Minimally invasive surgical therapy establishing a loop ileostomy and antibiotic installation via enema has to be considered as early surgical intervention. Fecal microbiotic transplantation is a new therapeutic option for recurrent infection. Provisions for prevention and control have to be established to avoid in-hospital spread of pathogenic agents. This includes isolation of patients, personalisation of instruments, restriction of in-hospital transports, protective clothing and gloves, strict hand washing and antibiotic stewardship (ABS).}, }
@article {pmid29189354, year = {2018}, author = {Mills, JP and Rao, K and Young, VB}, title = {Probiotics for prevention of Clostridium difficile infection.}, journal = {Current opinion in gastroenterology}, volume = {34}, number = {1}, pages = {3-10}, pmid = {29189354}, issn = {1531-7056}, support = {R21 AI120599/AI/NIAID NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; }, mesh = {Clinical Trials as Topic ; *Clostridioides difficile ; Clostridium Infections/diet therapy/microbiology/*prevention &amp; control/*therapy ; Enterocolitis, Pseudomembranous/diet therapy/microbiology/*prevention &amp; control/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Microbiota/physiology ; Primary Prevention/*methods ; Probiotics/*therapeutic use ; }, abstract = {PURPOSE OF REVIEW: Probiotics may prevent Clostridium difficile infection (CDI), a leading healthcare-associated infection in the United States. However, prior studies were limited by heterogeneity in products and patient populations. Recent clinical evidence and new approaches to probiotic development are reviewed.<br><br>RECENT FINDINGS: Probiotic use may reduce incident CDI in high-risk populations by as much as 50%, though prior clinical trials have yielded conflicting results. Combining probiotics with prebiotics improves growth and engraftment in the host. Bacillus clausii and Lactobacillus reuteri secrete compounds that directly inhibit C. difficile. Organisms that produce secondary bile acids, such as Clostridium scindens, enhance C. difficile colonization resistance. Nontoxigenic C. difficile, which provides nutritional niche competition, may prevent CDI. Refinements to fecal microbiota transplantation (FMT) blur the line between probiotics and FMT. These include a quality-controlled stool product (RBX2660), purified Firmicutes spores (SER-109) and sterile fecal filtrate. Bacteriophages may treat CDI but have unknown safety and efficacy in humans.<br><br>SUMMARY: There have been a number of advances in probiotics and our understanding of their role in prevention of CDI, but a number of important safety and efficacy questions remain. An improved understanding of the native microbiota structure and function will allow for continued development of rationally designed probiotic therapy to provide enhanced protection against CDI.}, }
@article {pmid29188472, year = {2018}, author = {Allegretti, JR and Kassam, Z and Chan, WW}, title = {Small Intestinal Bacterial Overgrowth: Should Screening Be Included in the Pre-fecal Microbiota Transplantation Evaluation?.}, journal = {Digestive diseases and sciences}, volume = {63}, number = {1}, pages = {193-197}, pmid = {29188472}, issn = {1573-2568}, support = {P30 DK034854/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile ; Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/*adverse effects ; Female ; Humans ; Intestine, Small/*microbiology ; Male ; Middle Aged ; Risk Factors ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is safe and effective for recurrent Clostridium difficile infection (rCDI) and often involves terminal ileal (TI) stool infusion. Patients report gastrointestinal (GI) symptoms post-FMT despite rCDI resolution. Small intestinal bacterial overgrowth (SIBO) screening is not routinely performed pre-FMT. The effect of donor/recipient SIBO status on FMT outcomes and post-FMT GI symptoms is unclear. We aim to evaluate the value of pre-FMT SIBO screening on post-FMT outcomes and symptoms.<br><br>METHODS: This was a prospective pilot study of consecutive adults with rCDI undergoing FMT by colonoscopy at a tertiary center. Routine pre-FMT screening and baseline lactulose breath tests (LBTs) were performed for donors and recipients. Positive LBT required a rise >&#xa0;20&#xa0;ppm in breath hydrogen or any methane level >&#xa0;10&#xa0;ppm within 90&#xa0;min. The presence of GI symptoms and CDI resolution were assessed 8&#xa0;weeks post-FMT. Fisher's exact/Student's t tests were performed for statistical analyses.<br><br>RESULTS: Twenty recipients (58.3&#xa0;years, 85% women) enrolled in the study. Fourteen (70%) FMTs involved TI stool infusion. Four (20%) recipients and six (30%) donors had positive LBT pre-FMT. At 8&#xa0;weeks post-FMT, 17 (85%) recipients had CDI resolution and five (25%) reported GI symptoms. Pre-FMT LBT result was not associated with post-FMT CDI resolution or GI symptoms. There was a trend toward increased GI symptoms among recipients receiving stool from LBT-positive donors (50 vs 14.2%, p&#xa0;=&#xa0;0.09).<br><br>CONCLUSIONS: FMT is effective and well tolerated for rCDI. Positive LBT in asymptomatic donors may have an effect on post-FMT GI symptoms. Larger studies are needed.}, }
@article {pmid29185252, year = {2017}, author = {Brunel, AS and Guery, B}, title = {Multidrug resistant (or antimicrobial-resistant) pathogens - alternatives to new antibiotics?.}, journal = {Swiss medical weekly}, volume = {147}, number = {}, pages = {w14553}, doi = {10.4414/smw.2017.14553}, pmid = {29185252}, issn = {1424-3997}, mesh = {Anti-Infective Agents/*therapeutic use ; Bacteriophages ; *Drug Resistance, Multiple, Bacterial ; Humans ; *Microbiota ; Probiotics ; *Quorum Sensing ; }, abstract = {For the last few decades, multidrug resistance has become an increasing concern for both Gram-positive and Gram-negative bacteria. The number of new molecules has dramatically decreased and antibiotic resistance is now a priority in the international community. Facing this new threat, a large number of new as well as "old" solutions are now being discussed in the medical community to propose an alternative to antibiotic treatments. A first option is to potentiate the effect of existing molecules through combinations to circumvent the individual molecule resistance. The second option is to neutralise either the infectious agent itself or its by-products using specific antibodies. A third option is to use the pathogen signaling mechanism and inhibit the production of virulence factor through quorum sensing inhibition. A fourth pathway would be to interact with the patient's microbiota using either probiotics or faecal transplantation to modulate the innate immune response and improve response to the infectious challenge, but also to act directly against colonisation by resistant bacteria by replacing the flora with susceptible strains. The last option is to target the bacteria using phage therapy. Phages are natural viruses that specifically infect target bacteria independently of any antibiotic-susceptibility profile. In this review, we will discuss each of these options and provide the scientific rationale and the available clinical data. In the majority of cases, these treatments represent an interesting approach but not the ultimate solution to multiresistance. Well-performed clinical trials are still missing and the major priority remains to promote good use and appropriate stewardship of antibiotics to decrease resistance.}, }
@article {pmid29183720, year = {2017}, author = {Staley, C and Khoruts, A and Sadowsky, MJ}, title = {Contemporary Applications of Fecal Microbiota Transplantation to Treat Intestinal Diseases in Humans.}, journal = {Archives of medical research}, volume = {48}, number = {8}, pages = {766-773}, doi = {10.1016/j.arcmed.2017.11.006}, pmid = {29183720}, issn = {1873-5487}, mesh = {Clostridium Infections/therapy ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Humans ; Intestinal Diseases/microbiology/*therapy ; Metabolic Syndrome/microbiology/therapy ; }, abstract = {The intestinal microbiota comprise an important organ that plays a vital role in host digestion, development, energy maintenance, hemostasis, and immunity. Disruption of the gut microbial community due to diet, lifestyle, or antibiotic exposure increases susceptibility to chronic infection and disease. Fecal microbiota transplantation (FMT) involves the transfer of gut microbiota from a healthy donor to a patient in order to restore normal diversity and function of the microbial community. This method has become a well established alternative therapy for the treatment of recurrent Clostridium difficile infection. Recent clinical trials and studies in animal models suggest promise for this method to treat inflammatory bowel diseases, as well as metabolic syndrome. In addition, due to signaling interactions between the gut microbiota and brain, FMT has been suggested as a potential treatment for some psychological disorders, including autism spectrum disorder. Importantly, advances in next-generation sequencing and multi-omics approaches are increasingly improving our understanding of the mechanisms by which FMT results in cure of these various conditions. In this review, we summarize the current applications of FMT and highlight potential future uses and current challenges in understanding and optimizing FMT procedures.}, }
@article {pmid29183074, year = {2017}, author = {Kao, D and Roach, B and Silva, M and Beck, P and Rioux, K and Kaplan, GG and Chang, HJ and Coward, S and Goodman, KJ and Xu, H and Madsen, K and Mason, A and Wong, GK and Jovel, J and Patterson, J and Louie, T}, title = {Effect of Oral Capsule- vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.}, journal = {JAMA}, volume = {318}, number = {20}, pages = {1985-1993}, pmid = {29183074}, issn = {1538-3598}, mesh = {*Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Capsules ; Clostridium Infections/prevention &amp; control/*therapy ; *Colonoscopy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Patient Satisfaction ; Quality of Life ; Secondary Prevention ; Young Adult ; }, abstract = {IMPORTANCE: Fecal microbiota transplantation (FMT) is effective in preventing recurrent Clostridium difficile infection (RCDI). However, it is not known whether clinical efficacy differs by route of delivery.<br><br>OBJECTIVE: To determine whether FMT by oral capsule is noninferior to colonoscopy delivery in efficacy.<br><br>Noninferiority, unblinded, randomized trial conducted in 3 academic centers in Alberta, Canada. A total of 116 adult patients with RCDI were enrolled between October 2014 and September 2016, with follow-up to December 2016. The noninferiority margin was 15%.<br><br>INTERVENTIONS: Participants were randomly assigned to FMT by capsule or by colonoscopy at a 1:1 ratio.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients without RCDI 12 weeks after FMT. Secondary outcomes included (1) serious and minor adverse events, (2) changes in quality of life by the 36-Item Short Form Survey on a scale of 0 (worst possible quality of life) to 100 (best quality of life), and (3) patient perception on a scale of 1 (not at all unpleasant) to 10 (extremely unpleasant) and satisfaction on a scale of 1 (best) to 10 (worst).<br><br>RESULTS: Among 116 patients randomized (mean [SD] age, 58 [19] years; 79 women [68%]), 105 (91%) completed the trial, with 57 patients randomized to the capsule group and 59 to the colonoscopy group. In per-protocol analysis, prevention of RCDI after a single treatment was achieved in 96.2% in both the capsule group (51/53) and the colonoscopy group (50/52) (difference, 0%; 1-sided 95% CI, -6.1% to infinity; P&#x2009;<&#x2009;.001), meeting the criterion for noninferiority. One patient in each group died of underlying cardiopulmonary illness unrelated to FMT. Rates of minor adverse events were 5.4% for the capsule group vs 12.5% for the colonoscopy group. There was no significant between-group difference in improvement in quality of life. A significantly greater proportion of participants receiving capsules rated their experience as "not at all unpleasant" (66% vs 44%; difference, 22% [95% CI, 3%-40%]; P&#x2009;=&#x2009;.01).<br><br>CONCLUSIONS AND RELEVANCE: Among adults with RCDI, FMT via oral capsules was not inferior to delivery by colonoscopy for preventing recurrent infection over 12 weeks. Treatment with oral capsules may be an effective approach to treating RCDI.<br><br>TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02254811.}, }
@article {pmid29183052, year = {2017}, author = {Rao, K and Young, VB and Malani, PN}, title = {Capsules for Fecal Microbiota Transplantation in Recurrent Clostridium difficile Infection: The New Way Forward or a Tough Pill to Swallow?.}, journal = {JAMA}, volume = {318}, number = {20}, pages = {1979-1980}, pmid = {29183052}, issn = {1538-3598}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; }, mesh = {*Capsules ; Clostridioides difficile ; Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Microbiota ; }, }
@article {pmid29179687, year = {2017}, author = {Verbeke, F and Janssens, Y and Wynendaele, E and De Spiegeleer, B}, title = {Faecal microbiota transplantation: a regulatory hurdle?.}, journal = {BMC gastroenterology}, volume = {17}, number = {1}, pages = {128}, pmid = {29179687}, issn = {1471-230X}, support = {131356//Agentschap voor Innovatie door Wetenschap en Technologie/ ; }, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; Europe ; *Fecal Microbiota Transplantation ; Humans ; *Legislation, Medical ; Recurrence ; United States ; }, abstract = {During faecal microbiota transplantation, stool from a healthy donor is transplanted to treat a variety of dysbiosis-associated gut diseases. Competent authorities are faced with the challenge to provide adequate regulation. Currently, regulatory harmonization is completely lacking and authorities apply non-existing to most stringent requirements. A regulatory approach for faecal microbiota transplantation could be inserting faecal microbiota transplantation in the gene-, cell- and tissue regulations, including the hospital exemption system in the European Advanced Therapy Medicinal Products regulation, providing a pragmatic and efficacy-risk balanced approach and granting all patients as a matter of principle access to this therapy.}, }
@article {pmid29179485, year = {2017}, author = {Zhang, T and Xiang, J and Cui, B and He, Z and Li, P and Chen, H and Xu, L and Ji, G and Nie, Y and Wu, K and Fan, D and Huang, G and Bai, J and Zhang, F}, title = {Cost-effectiveness analysis of fecal microbiota transplantation for inflammatory bowel disease.}, journal = {Oncotarget}, volume = {8}, number = {51}, pages = {88894-88903}, pmid = {29179485}, issn = {1949-2553}, abstract = {There is a lack of health economics evidence on the use of fecal microbiota transplantation (FMT) for inflammatory bowel disease (IBD). This study aims to evaluate the cost-effectiveness before (with conventional therapy) and after introducing FMT for treating IBD. 104 patients with IBD received FMT were recruited. Health status was evaluated by European dimension health table (ED-5Q). Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NB) were calculated by different age groups, genders, smoking status, and disease subtypes. The willingness-to-pay threshold was set to the value equal to three times China's per capita GDP (141240 CNY/QALY, 2014). From the health-care perspective, FMT strategy was 73% likely to be cost-effective compared with the conventional therapy before FMT with an ICER of -185712 CNY/QALY and a positive NB of CNY 45150. From the societal perspective, FMT strategy was 75% likely to be cost-effective with an ICER of -207417 CNY/QALY and a positive NB of CNY 48395. Moreover, younger patients (≤ 24), females, non-smokers and Crohn's disease (CD) achieved more benefits. This study for the first time demonstrated that FMT showed its cost-effectiveness, especially on improving the life quality and decreasing the medical and societal cost, for the moderate to severe IBD in a Chinese cohort.}, }
@article {pmid29173524, year = {2017}, author = {Browne, AS and Kelly, CR}, title = {Fecal Transplant in Inflammatory Bowel Disease.}, journal = {Gastroenterology clinics of North America}, volume = {46}, number = {4}, pages = {825-837}, doi = {10.1016/j.gtc.2017.08.005}, pmid = {29173524}, issn = {1558-1942}, mesh = {*Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Observational Studies as Topic ; Randomized Controlled Trials as Topic ; }, abstract = {Patients with inflammatory bowel disease (IBD) have differences in their gastrointestinal microbiome compared with healthy individuals, although it is unclear whether this is a cause or consequence of chronic inflammation. There is hope that manipulation of the gut microbiome through fecal microbiota transplant (FMT), commonly used to treat patients with Clostridium difficile infection, may also be an effective therapy in IBD. This article reviews the evidence supporting FMT in IBD, including case reports, case series, and randomized controlled trials. The article also focuses on questions of safety and speculates on the future of this therapy.}, }
@article {pmid29173517, year = {2017}, author = {Basson, AR and Lam, M and Cominelli, F}, title = {Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches.}, journal = {Gastroenterology clinics of North America}, volume = {46}, number = {4}, pages = {689-729}, pmid = {29173517}, issn = {1558-1942}, support = {T32 DK083251/DK/NIDDK NIH HHS/United States ; P01 DK091222/DK/NIDDK NIH HHS/United States ; P30 DK097948/DK/NIDDK NIH HHS/United States ; R37 DK042191/DK/NIDDK NIH HHS/United States ; R56 DK042191/DK/NIDDK NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; R56 DK055812/DK/NIDDK NIH HHS/United States ; R01 DK055812/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Caseins/therapeutic use ; *Complementary Therapies ; *Diet ; *Dietary Supplements ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*therapy ; Medical Marijuana/therapeutic use ; Peptide Fragments/therapeutic use ; Phytochemicals/therapeutic use ; Polysaccharides/therapeutic use ; Prebiotics ; Probiotics/*therapeutic use ; Psychophysiology ; }, abstract = {The human gut microbiome exerts a major impact on human health and disease, and therapeutic gut microbiota modulation is now a well-advocated strategy in the management of many diseases, including inflammatory bowel disease (IBD). Scientific and clinical evidence in support of complementary and alternative medicine, in targeting intestinal dysbiosis among patients with IBD, or other disorders, has increased dramatically over the past years. Delivery of "artificial" stool replacements for fecal microbiota transplantation (FMT) could provide an effective, safer alternative to that of human donor stool. Nevertheless, optimum timing of FMT administration in IBD remains unexplored, and future investigations are essential.}, }
@article {pmid29169776, year = {2017}, author = {Sans, A and Mege, D and Sielezneff, I}, title = {One-stage dynamic graciloplasty for anal incontinence.}, journal = {Journal of visceral surgery}, volume = {154}, number = {6}, pages = {437-448}, doi = {10.1016/j.jviscsurg.2017.10.014}, pmid = {29169776}, issn = {1878-7886}, mesh = {Anal Canal/physiopathology/*surgery ; Electric Stimulation Therapy/*instrumentation/methods ; Fecal Incontinence/rehabilitation/*surgery ; Female ; Follow-Up Studies ; Gracilis Muscle/surgery/*transplantation ; Humans ; *Implantable Neurostimulators ; Male ; Postoperative Care/methods ; *Quality of Life ; Plastic Surgery Procedures/methods ; Treatment Outcome ; }, }
@article {pmid29162935, year = {2018}, author = {Nimgaonkar, I and Ding, Q and Schwartz, RE and Ploss, A}, title = {Hepatitis E virus: advances and challenges.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {15}, number = {2}, pages = {96-110}, pmid = {29162935}, issn = {1759-5053}, support = {R21 AI117213/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cells, Cultured ; Disease Models, Animal ; Global Health ; Hepatitis E/*epidemiology/therapy/transmission ; Hepatitis E virus/chemistry/genetics/physiology ; Hepatocytes/virology ; Pluripotent Stem Cells/virology ; Viral Hepatitis Vaccines ; Viral Proteins/physiology ; Viral Tropism/physiology ; Virion/chemistry/physiology ; }, abstract = {At least 20 million hepatitis E virus (HEV) infections occur annually, with >3 million symptomatic cases and ∼60,000 fatalities. Hepatitis E is generally self-limiting, with a case fatality rate of 0.5-3% in young adults. However, it can cause up to 30% mortality in pregnant women in the third trimester and can become chronic in immunocompromised individuals, such as those receiving organ transplants or chemotherapy and individuals with HIV infection. HEV is transmitted primarily via the faecal-oral route and was previously thought to be a public health concern only in developing countries. It is now also being frequently reported in industrialized countries, where it is transmitted zoonotically or through organ transplantation or blood transfusions. Although a vaccine for HEV has been developed, it is only licensed in China. Additionally, no effective, non-teratogenic and specific treatments against HEV infections are currently available. Although progress has been made in characterizing HEV biology, the scarcity of adequate experimental platforms has hampered further research. In this Review, we focus on providing an update on the HEV life cycle. We will further discuss existing cell culture and animal models and highlight platforms that have proven to be useful and/or are emerging for studying other hepatotropic (viral) pathogens.}, }
@article {pmid29161082, year = {2017}, author = {Gérard, P}, title = {Gut Microbiome and Obesity. How to Prove Causality?.}, journal = {Annals of the American Thoracic Society}, volume = {14}, number = {Supplement_5}, pages = {S354-S356}, doi = {10.1513/AnnalsATS.201702-117AW}, pmid = {29161082}, issn = {2325-6621}, mesh = {Animals ; Causality ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Mice ; Obesity/*microbiology ; }, abstract = {In recent years, the gut microbiota (the microorganisms that live in our digestive tract) has become an area of great interest. Indeed, this intestinal microbial community performs essential functions in maintaining our health, and has been proven to influence host physiology and metabolism. Thereby, dysregulation of this gut microbiota may be implicated in the development of various diseases, including obesity. However, studies rarely assess causality, which requires the use of germ-free animals and microbiota transplant. Using these strategies, some gut microbiota were shown to confer obesity and associated metabolic disorders to mice, suggesting a causative link between gut bacteria and metabolic diseases.}, }
@article {pmid29158182, year = {2018}, author = {Ankcorn, MJ and Ijaz, S and Haywood, B and Neuberger, J and Elsharkawy, AM and Maggs, J and Tedder, RS}, title = {Confirmation of specificity of reactivity in a solid phase ELISA for the detection of hepatitis E viral antigen improves utility of the assay.}, journal = {Journal of virological methods}, volume = {252}, number = {}, pages = {42-48}, doi = {10.1016/j.jviromet.2017.11.007}, pmid = {29158182}, issn = {1879-0984}, mesh = {*Enzyme-Linked Immunosorbent Assay ; Feces/virology ; Hepatitis Antibodies/blood ; Hepatitis B e Antigens/*isolation &amp; purification ; Hepatitis E/*diagnosis/immunology ; Hepatitis E virus ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Neutralization Tests ; RNA, Viral/genetics ; Reagent Kits, Diagnostic ; Sensitivity and Specificity ; }, abstract = {Genotype 3 hepatitis E virus (HEV) can lead to persistent infections in immunocompromised hosts. A recently available commercial assay for the detection of HEV antigen (HEV-Ag ELISA, Wantai diagnostics) may enable the study of HEV-Ag dynamics in such persistent infections, however currently there is no confirmatory test available. We generated a putative neutralising reagent from a pool of four convalescent blood donor samples and explored neutralising activity against HEV antigens from clinical samples, HEV tissue-culture and virus-like particles. Using this neutralisation method we were able to differentiate true reactivity from non-specific reactivity in plasma, stool and urine samples. This could also facilitate the introduction of HEV-Ag detection as a screening assay or the study of HEV-Ag in different body fluids.}, }
@article {pmid29158082, year = {2019}, author = {Bamba, S and Nishida, A and Imaeda, H and Inatomi, O and Sasaki, M and Sugimoto, M and Andoh, A}, title = {Successful treatment by fecal microbiota transplantation for Japanese patients with refractory Clostridium difficile infection: A prospective case series.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {52}, number = {4}, pages = {663-666}, doi = {10.1016/j.jmii.2017.08.027}, pmid = {29158082}, issn = {1995-9133}, mesh = {Aged ; Aged, 80 and over ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/*therapy ; Colonoscopy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Japan ; Male ; Metronidazole/therapeutic use ; Prospective Studies ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {We prospectively enrolled four Japanese patients with refractory Clostridium difficile infection (CDI) and were treated with a single fecal microbiota transplantation (FMT). The average age of the patients was 83.7 years. All patients had a successful clinical course for up to 3 months without any adverse events.}, }
@article {pmid29157127, year = {2018}, author = {Lee, H and Lee, Y and Kim, J and An, J and Lee, S and Kong, H and Song, Y and Lee, CK and Kim, K}, title = {Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice.}, journal = {Gut microbes}, volume = {9}, number = {2}, pages = {155-165}, pmid = {29157127}, issn = {1949-0984}, mesh = {Age Factors ; Animals ; Bacteria/classification/drug effects ; Blood Glucose/drug effects ; Body Weight/drug effects ; Diet, High-Fat/*adverse effects ; Disease Models, Animal ; Epididymis/drug effects/*immunology ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/physiology ; Gene Expression Regulation/immunology ; Interleukin-1beta/genetics ; Interleukin-6/genetics ; Lipid Metabolism/drug effects ; Male ; Metformin/*pharmacology/therapeutic use ; Mice ; Mice, Inbred C57BL ; Obesity/drug therapy/immunology/*metabolism/*microbiology ; }, abstract = {The gut microbiota is a contributing factor in obesity-related metabolic disorders. The effect of metformin on the gut microbiota has been reported; however, the relationship between the gut microbiota and the mechanism of action of metformin in elderly individuals is unclear. In this study, the effect of metformin on the gut microbiota was investigated in aged obese mice. The abundance of the genera Akkermansia, Bacteroides, Butyricimonas, and Parabacteroides was significantly increased by metformin in mice fed a high-fat diet. Metformin treatment decreased the expression of IL-1β and IL-6 in epididymal fat, which was correlated with the abundance of various bacterial genera. In addition, both fecal microbiota transplantation from metformin-treated mice and extracellular vesicles of Akkermansia muciniphila improved the body weight and lipid profiles of the mice. Our findings suggest that modulation of the gut microbiota by metformin results in metabolic improvements in aged mice, and that these effects are associated with inflammatory immune responses.}, }
@article {pmid29152407, year = {2017}, author = {Abadi, ATB}, title = {Fecal microbiota transplantation against irritable bowel syndrome? Rigorous randomized clinical trials are required.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {8}, number = {4}, pages = {208-209}, pmid = {29152407}, issn = {2150-5349}, abstract = {Halkjær et al searched systematically nine articles including 48 patients, and concluded that fecal microbiota transplantation (FMT) can be an ideal treatment option for irritable bowel syndrome (IBS) subjects. Regardless of the few successes in current traditional therapies (change in diet, herbal medicine and antibiotics) in IBS, a sharp increase in interests in the FMT option has been reported in the current century. However, there is a long list of unclear issues concerning the application of FMT for the treatment of IBS. Route of delivery and optimum dosage are the major concerns to consider before using in clinical practice.}, }
@article {pmid29151426, year = {2017}, author = {Han, Y and Leng, Y and Yao, G}, title = {[Effects of antibiotics on intestinal microflora and intestinal mucosal barrier function and its mechanisms].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {29}, number = {11}, pages = {1047-1051}, doi = {10.3760/cma.j.issn.2095-4352.2017.11.019}, pmid = {29151426}, issn = {2095-4352}, mesh = {Anti-Bacterial Agents ; Gastrointestinal Diseases ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa ; Probiotics ; }, abstract = {Antibiotics are the cornerstone to cure infectious diseases, however, it also destroys the intestinal inherent microflora, and may cause serious gastrointestinal dysfunction, such as abdominal distension, diarrhea, mucosal barrier damage etc. In severe conditions, it may induce intestinal sepsis. With the development of the human microbiology group program and the popularity of microbial sequencing technology, people can comprehend the effects of antibiotics on intestinal flora deeply, meanwhile the traditional biomedical model (the basis of bacterial disease) is questioned. It presents the effects and mechanisms of antibiotics on intestinal microflora and intestinal mucosal barrier function in detail and demonstrates the feasibility by the treatment of probiotics and fecal transplantation to construct "health-promoting microbes" to adjust gastrointestinal function, in addition, it can promote the rational use of antibiotics.}, }
@article {pmid29151253, year = {2018}, author = {Karolewska-Bochenek, K and Grzesiowski, P and Banaszkiewicz, A and Gawronska, A and Kotowska, M and Dziekiewicz, M and Albrecht, P and Radzikowski, A and Lazowska-Przeorek, I}, title = {A Two-Week Fecal Microbiota Transplantation Course in Pediatric Patients with Inflammatory Bowel Disease.}, journal = {Advances in experimental medicine and biology}, volume = {1047}, number = {}, pages = {81-87}, doi = {10.1007/5584_2017_123}, pmid = {29151253}, issn = {0065-2598}, mesh = {Adolescent ; Child ; Crohn Disease/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Male ; Microbiota ; Remission Induction ; Treatment Outcome ; }, abstract = {Dysbiosis plays a major role in the etiology of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) is a new promising option for IBD treatment. We aimed to assess the effectiveness of a two-week FMT course in children with IBD. Ten patients, 10-17 years of age with moderate to severe IBD received a course of eight doses of freshly prepared FMT via a naso-duodenal tube or gastroscopy. All of the patients had pancolitis. There were eight cases of ulcerative colitis (UC) and two of Crohn's disease (CD). Disease activity was evaluated using the Pediatric UC Activity Index (PUCAI) and Pediatric CD Activity Index (PCDAI) for UC and CD, respectively, CRP, and fecal calprotectin on the day before the first infusion and then on the day before the next course of FMT. Clinical response, defined as a decrease of 15 points in either index, was observed in 9/10 patients (seven UC and two CD). Clinical remission, defined as a PCDAI score ≤ 10 and PUCAI score < 10 measured at the same time point, was observed in 3/8 UC patients and 2/2 CD patients. Side effects observed were self-limiting and benign. We conclude that a short, intensive course of FMT has a beneficial effect on UC and CD colitis. FMT was well-tolerated and safe. Nonetheless, an optimal protocol of FMT administration is crucial for treatment efficacy.}, }
@article {pmid29142271, year = {2017}, author = {Stadlbauer, V and Horvath, A and Ribitsch, W and Schmerböck, B and Schilcher, G and Lemesch, S and Stiegler, P and Rosenkranz, AR and Fickert, P and Leber, B}, title = {Structural and functional differences in gut microbiome composition in patients undergoing haemodialysis or peritoneal dialysis.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {15601}, pmid = {29142271}, issn = {2045-2322}, support = {P 24362/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Aged ; C-Reactive Protein/genetics ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Inflammation/genetics/*microbiology/pathology ; Kidney Failure, Chronic/*genetics/microbiology/pathology ; Male ; Middle Aged ; Peritoneal Dialysis/adverse effects ; Renal Dialysis/adverse effects ; }, abstract = {Complications of end-stage renal disease (ESRD) are critically related to inflammation. The gut microbiome is a key driver of inflammation. Since dialysis modalities may differently influence the gut microbiome, we aimed to compare the effects of haemodialysis (HD) and peritoneal dialysis (PD) on patients' gut microbiome composition and function. We therefore studied faecal microbiome composition and function as well as inflammation and gut permeability in 30 patients with ESRD (15 HD, 15 PD) and compared to 21 healthy controls. We found an increase in potentially pathogenic species and a decrease in beneficial species in patients on HD and to a lesser extend in patients on PD when compared to controls. These changes in taxonomic composition also resulted in differences in predicted metagenome functions of the faecal microbiome. In HD but not in PD, changes in microbiome composition were associated with an increase in c-reactive protein (CRP) but not with intestinal inflammation or gut permeability. In conclusion microbiome composition in ESRD differs from healthy controls but also between modes of dialysis. These differences are associated with systemic inflammation and cannot completely be explained by dialysis vintage. The mode of renal replacement therapy seems to be an important driver of dysbiosis in ESRD.}, }
@article {pmid29140453, year = {2017}, author = {Quraishi, MN and Critchlow, T and Bhala, N and Sharma, N and Iqbal, T}, title = {Faecal transplantation for IBD management-pitfalls and promises.}, journal = {British medical bulletin}, volume = {124}, number = {1}, pages = {181-190}, doi = {10.1093/bmb/ldx040}, pmid = {29140453}, issn = {1471-8391}, support = {EME/13/179/01/DH_/Department of Health/United Kingdom ; }, mesh = {Evidence-Based Medicine ; *Fecal Microbiota Transplantation/methods/trends ; Gastrointestinal Microbiome/immunology/physiology ; Humans ; Inflammatory Bowel Diseases/immunology/microbiology/*therapy ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) as a potential treatment for inflammatory bowel disease (IBD) is an area of active current research, having been stimulated by the remarkable efficacy of FMT in treatment of Clostridium difficile-associated colitis.<br><br>SOURCES OF DATA: This review is based on data from numerous case series on FMT in IBD since 1989 and results of four RCTs in ulcerative colitis (UC); three fully published.<br><br>AREAS OF AGREEMENT: Early signals of short to medium-term efficacy of FMT for UC are promising.<br><br>AREAS OF CONTROVERSY: Methodology, underlying mechanisms and questions regarding safety of FMT remain controversial.<br><br>GROWING POINTS: Many trials of FMT in adults and children are currently recruiting.<br><br>Future trials of FMT will likely revisit Crohn's disease and patients undergoing pouch surgery. Advances in microbial culture complementing genetic sequencing and investigations into the virome and mycobiome in IBD will be of great future interest.}, }
@article {pmid29138633, year = {2017}, author = {Pei, G and Lv, W and Li, X and Zhang, G and Zhang, J}, title = {Influence of SPK with Enteric Drainage on the Pancreatic Exocrine Function in Diabetic Patients with Uremia.}, journal = {International journal of endocrinology}, volume = {2017}, number = {}, pages = {3709306}, pmid = {29138633}, issn = {1687-8337}, abstract = {OBJECTIVE: This study aimed to determine the use of fecal elastase in evaluating the effect of simultaneous pancreas-kidney transplantation with enteric drainage on the pancreatic exocrine function of diabetic patients with uremia.<br><br>METHODS: A total of 19 patients with simultaneous pancreas-kidney transplantation (SPK) with enteric drainage, 31 diabetic patients with uremia (chronic renal failure (CRF)), 22 diabetic patients with uremia who underwent renal transplantation (RT), and 20 normal individuals (CON) were included in the study. Pancreatic exocrine insufficiency was determined using fecal elastase. Results. The fecal pancreatic elastase level in SPK patients with enteric drainage was 479&#x2009;&#x3bc;g/g, which was significantly higher than 229&#x2009;&#x3bc;g/g in CRF patients and 197&#x2009;&#x3bc;g/g in RT patients. Using 200&#x2009;&#x3bc;g/g as the established threshold, a reduced fecal pancreatic elastase level was found in 14/31 of CRF patients, 12/22 of RT patients, 1/19 of SPK patients with enteric drainage, and 1/20 of CON patients. The correlation analysis revealed a significant association between fecal elastase and glycosylated hemoglobin.<br><br>CONCLUSIONS: The present study indicated that SPK with enteric drainage improves pancreatic endocrine and exocrine functions. Fecal elastase may be a clinically relevant means to determine the therapeutic effects.}, }
@article {pmid29134299, year = {2018}, author = {Friedman-Korn, T and Livovsky, DM and Maharshak, N and Aviv Cohen, N and Paz, K and Bar-Gil Shitrit, A and Goldin, E and Koslowsky, B}, title = {Fecal Transplantation for Treatment of Clostridium Difficile Infection in Elderly and Debilitated Patients.}, journal = {Digestive diseases and sciences}, volume = {63}, number = {1}, pages = {198-203}, pmid = {29134299}, issn = {1573-2568}, mesh = {Aged ; Aged, 80 and over ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a new technique recently introduced to treat recurrent Clostridium difficile infection (CDI). Little is known about the efficacy and risks of FMT in elderly and ill patients.<br><br>AIM: To investigate FMT efficacy in ill and elderly patients compared to conventional treatment.<br><br>METHODS: The study comprised two groups of patients between 2012 and 2016 with recurrent CDI at two medical centers in Israel. The study group received FMT and the controls conventional therapy. The primary end points were CDI recurrence, length of hospitalization, and short-term survival.<br><br>RESULTS: Thirty-four patients altogether, (21 females, mean age 82&#xa0;years) participated, 11 received FMT and 23 controls. Demographics and clinical characteristics were similar between the two groups. Comorbidity indexes, i.e., Charlson index was high in both groups. In the FMT group, 10/11 (90%) patients showed clinical improvement 3&#xa0;days after initiating treatment compared to 9/23 (39%) in the control group, p&#xa0;=&#xa0;0.02. Survival at 2&#xa0;months did not differ between the groups (FMT 54%, Control 50%, p&#xa0;=&#xa0;0.816), but mean survival in the FMT group was higher than in the control (12 vs. 4&#xa0;months, respectively, p&#xa0;=&#xa0;0.015). Two significant adverse events from the FMT group included suspected aspirations, both occurring during gastroscopy route of administration.<br><br>CONCLUSIONS: FMT is effective for elderly and very ill patients. Safety is a concern, but is rare even in patients with much comorbidity. Colonoscopy may be the preferred route of FMT infusion.}, }
@article {pmid29133078, year = {2018}, author = {Darnaud, M and Dos Santos, A and Gonzalez, P and Augui, S and Lacoste, C and Desterke, C and De Hertogh, G and Valentino, E and Braun, E and Zheng, J and Boisgard, R and Neut, C and Dubuquoy, L and Chiappini, F and Samuel, D and Lepage, P and Guerrieri, F and Doré, J and Bréchot, C and Moniaux, N and Faivre, J}, title = {Enteric Delivery of Regenerating Family Member 3 alpha Alters the Intestinal Microbiota and Controls Inflammation in Mice With Colitis.}, journal = {Gastroenterology}, volume = {154}, number = {4}, pages = {1009-1023.e14}, doi = {10.1053/j.gastro.2017.11.003}, pmid = {29133078}, issn = {1528-0012}, mesh = {Animals ; Bacteria/classification/growth &amp; development/*metabolism ; Colitis/chemically induced/metabolism/microbiology/*prevention &amp; control ; Colon/*metabolism/microbiology ; Dextran Sulfate ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Hepatocytes/*metabolism ; Humans ; Mice, Inbred C57BL ; Mice, Transgenic ; Microbial Viability ; Oxidative Stress/drug effects ; Pancreatitis-Associated Proteins/genetics/*metabolism ; Reactive Oxygen Species/metabolism ; Time Factors ; Trinitrobenzenesulfonic Acid ; }, abstract = {BACKGROUND &amp; AIMS: Paneth cell dysfunction causes deficiencies in intestinal C-type lectins and antimicrobial peptides, which leads to dysbiosis of the intestinal microbiota, alters the mucosal barrier, and promotes development of inflammatory bowel diseases. We investigated whether transgenic (TG) expression of the human regenerating family member 3 alpha gene (REG3A) alters the fecal microbiota and affects development of colitis in mice.<br><br>METHODS: We performed studies with C57BL/6 mice that express human regenerating family member 3 alpha (hREG3A) in hepatocytes, via the albumin gene promoter. In these mice, hREG3A travels via the bile to the intestinal lumen. Some mice were given dextran sodium sulfate (DSS) to induce colitis. Feces were collected from mice and the composition of the microbiota was analyzed by 16S ribosomal RNA sequencing. The fecal microbiome was also analyzed from mice that express only 1 copy of human REG3A transgene but were fed feces from control mice (not expressing hREG3A) as newborns. Mice expressing hREG3A were monitored for DSS-induced colitis after cohousing or feeding feces from control mice. Colitis was induced in another set of control and hREG3A-TG mice by administration of trinitrobenzene sulfonic acid; some mice were given intrarectal injections of the hREG3A protein. Colon tissues were collected from mice and analyzed by histology and immunohistochemistry to detect mucin 2, as well as by 16S ribosomal RNA fluorescence in situ hybridization, transcriptional analyses, and quantitative polymerase chain reaction. We measured levels of reactive oxygen species (ROS) in bacterial cultures and fecal microbiota using 2',7'-dichlorofluorescein diacetate and flow cytometry.<br><br>RESULTS: The fecal microbiota of mice that express hREG3A had a significant shift in composition, compared with control mice, with enrichment of Clostridiales (Ruminococcaceae, Lachnospiraceae) and depletion of Bacteroidetes (Prevotellaceae); the TG mice developed less-severe colitis following administration of DSS than control mice, associated with preserved gut barrier integrity and reduced bacterial translocation, epithelial inflammation, and oxidative damage. A similar shift in the composition of the fecal microbiota occurred after a few months in TG mice heterozygous for REG3A that harbored a wild-type maternal microbiota at birth; these mice developed less-severe forms of colitis following DSS administration. Cohoused and germ-free mice fed feces from REG3A-TG mice and given DSS developed less-severe forms of colitis and had reduced lipopolysaccharide activation of the toll-like receptor 4 and increased survival times compared with mice not fed feces from REG3A-TG mice. REG3A TG mice developed only mild colonic inflammation after exposure to 2,4,6-trinitrobenzene sulfonic acid, compared with control mice. Control mice given intrarectal hREG3A and exposed to 2,4,6-trinitrobenzene sulfonic acid showed less colon damage and inflammation than mice not given intrarectal hREG3A. Fecal samples from REG3A-TG mice had lower levels of ROS than feces from control mice during DSS administration. Addition of hREG3A to bacterial cultures reduced levels of ROS and increased survival of oxygen-sensitive commensal bacteria (Faecalibacterium prausnitzii and Roseburia intestinalis).<br><br>CONCLUSIONS: Mice with hepatocytes that express hREG3A, which travels to the intestinal lumen, are less sensitive to colitis than control mice. We found hREG3A to alter the colonic microbiota by decreasing levels of ROS. Fecal microbiota from REG3A-TG mice protect non-TG mice from induction of colitis. These findings indicate a role for reduction of oxidative stress in preserving the gut microbiota and its ability to prevent inflammation.}, }
@article {pmid29132532, year = {2017}, author = {Irwin, G and Mayans, L and Kellerman, R}, title = {Emerging Topics in Gastroenterology.}, journal = {Primary care}, volume = {44}, number = {4}, pages = {733-742}, doi = {10.1016/j.pop.2017.07.008}, pmid = {29132532}, issn = {1558-299X}, mesh = {Colitis, Microscopic/physiopathology/therapy ; Eosinophilic Esophagitis/physiopathology/therapy ; Fecal Microbiota Transplantation/methods ; *Gastroenterology ; Gastrointestinal Microbiome/physiology ; Humans ; Primary Health Care ; Probiotics/pharmacology ; Vomiting/physiopathology/therapy ; }, abstract = {The bacteria and fungi in the human gut make up a community of microorganisms that lives in symbiosis with humans, engaging in numerous diverse interactions that influence health. This article outlines the current knowledge on emerging topics in gastroenterology, including microbiome and probiotics, fecal microbiota transplantation, cyclic vomiting syndrome, eosinophilic esophagitis, and microscopic colitis.}, }
@article {pmid29130220, year = {2017}, author = {Li, N and Tian, H}, title = {[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {20}, number = {10}, pages = {1104-1108}, pmid = {29130220}, issn = {1671-0274}, mesh = {Clostridioides difficile ; Clostridium Infections ; Fecal Microbiota Transplantation/*trends ; Feces ; Gastrointestinal Diseases/*therapy ; Humans ; Prospective Studies ; Randomized Controlled Trials as Topic ; Retrospective Studies ; }, abstract = {Fecal microbiota transplantation (FMT), also known as fecal bacteriotherapy or fecal infusion, consists of injection of a liquid filtrate of feces from a healthy donor into the gastrointestinal tract of a recipient individual. FMT has been proposed as a therapeutic approach for functional diseases of the gastrointestinal tract by reestablishment of a wide diversity of intestinal flora. Clostridium difficile infection (CDI) treatment guideline from American Gastroenterology Association (AGA) recommends that FMT can be used as the treatment protocols of relapse CDI. Numerous case reports, retrospective case series, and randomized controlled trials have shown the benefit of FMT in patients with functional bowel disorders, including inflammatory bowel disease, irritable bowel syndrome and constipation, etc. Evidence regarding the safety of FMT is relatively limited because the very rapid adoption of FMT as a therapeutic modality for CDI occurred before the performance of large, long prospective trials that are typically conducted to assess the safety of new interventions. Potential adverse events can be categorized as short-term and long-term, and short-term events can further be divided into those related to the method of FMT delivery (colonoscopy, sedation) and those related to the FMT itself. Due to the recent emergence of FMT, little data exist regarding long-term events and many safety concerns are speculative. Capsulized FMT therapy solves the clinical problems associated with the use of fresh FMT suspensions for long-term maintenance i.e. repeat transplantation and invasive procedures, which is of great significance to optimize the traditional FMT clinical strategy. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current "whole-stool" transplants to increase safety and tolerability. Encapsulated formulations, full-spectrum stool-based products, and defined microbial consortia are all in the immediate future. Although challenges exist, regulatory agencies have been willing to work with stakeholders and will continue to evolve and adapt policy as therapeutics based on human gut microbiota research emerge.}, }
@article {pmid29124320, year = {2018}, author = {Witkowski, M and Witkowski, M and Gagliani, N and Huber, S}, title = {Recipe for IBD: can we use food to control inflammatory bowel disease?.}, journal = {Seminars in immunopathology}, volume = {40}, number = {2}, pages = {145-156}, pmid = {29124320}, issn = {1863-2300}, support = {337251//FP7 Ideas: European Research Council/International ; 715271//FP7 Ideas: European Research Council/International ; }, mesh = {Animals ; *Diet ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Immunity, Mucosal/physiology ; Inflammatory Bowel Diseases/*diet therapy/*immunology/microbiology/*physiopathology ; Intestinal Mucosa/immunology/microbiology/physiopathology ; Probiotics/pharmacology ; }, abstract = {The mucosal immune system and the microbiota in the intestinal tract have recently been shown to play a key role in the pathogenesis of inflammatory bowel disease (IBD). Both of these can be influenced by food. Thus, we propose dietary intervention as a therapeutic option for IBD. In this review, we discuss the interaction of the intestinal mucosal immune system and the intestinal microbiota in the context of IBD. In addition, we discuss the impact of food components on immune responses in IBD. Finally, we address the current evidence of how this interaction (i.e., immune system-microbiota) can be modulated by food components, pre/probiotics, and fecal microbiota transplantation (FMT) and how these approaches can support intestinal homeostasis. By gathering the vast amount of literature available on the impact of food on IBD, we aim to distinguish between scientifically sound data and theories, which have not been included in this review.}, }
@article {pmid29124041, year = {2017}, author = {Li, HL and Lu, L and Wang, XS and Qin, LY and Wang, P and Qiu, SP and Wu, H and Huang, F and Zhang, BB and Shi, HL and Wu, XJ}, title = {Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {7}, number = {}, pages = {455}, pmid = {29124041}, issn = {2235-2988}, mesh = {Animals ; Antigens, CD/metabolism ; Bacteria/classification/drug effects/genetics/metabolism ; Body Weight/drug effects ; Cadherins/metabolism ; Cell Adhesion Molecules/metabolism ; Chemokines/*metabolism ; Colon/metabolism/pathology ; Cytokines/*metabolism ; Fecal Microbiota Transplantation ; Feces/microbiology ; Fluorouracil/*adverse effects ; Gastrointestinal Microbiome/*drug effects ; Immunohistochemistry ; Inflammation/complications/pathology ; Intercellular Adhesion Molecule-1/metabolism ; Intestinal Mucosa/*metabolism/pathology ; Intestines/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinases/metabolism ; Mucositis/chemically induced/*metabolism/*microbiology/pathology ; NF-kappa B/metabolism ; RNA, Ribosomal, 16S/genetics ; Receptors, Cell Surface/metabolism ; Vascular Cell Adhesion Molecule-1/metabolism ; Zonula Occludens-1 Protein/metabolism ; }, abstract = {Disturbed homeostasis of gut microbiota has been suggested to be closely associated with 5-fluorouracil (5-Fu) induced mucositis. However, current knowledge of the overall profiles of 5-Fu-disturbed gut microbiota is limited, and so far there is no direct convincing evidence proving the causality between 5-Fu-disturbed microbiota and colonic mucositis. In mice, in agreement with previous reports, 5-Fu resulted in severe colonic mucositis indicated by weight loss, diarrhea, bloody stool, shortened colon, and infiltration of inflammatory cells. It significantly changed the profiles of inflammatory cytokines/chemokines in serum and colon. Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and VE-Cadherin were increased. While tight junction protein occludin was reduced, however, zonula occludens-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were increased in colonic tissues of 5-Fu treated mice. Meanwhile, inflammation related signaling pathways including NF-κB and mitogen activated protein kinase (MAPKs) in the colon were activated. Further study disclosed that 5-Fu diminished bacterial community richness and diversity, leading to the relative lower abundance of Firmicutes and decreased Firmicutes/Bacteroidetes (F/B) ratio in feces and cecum contents. 5-Fu also reduced the proportion of Proteobacteria, Tenericutes, Cyanobacteria, and Candidate division TM7, but increased that of Verrucomicrobia and Actinobacteria in feces and/or cecum contents. The fecal transplant from healthy mice prevented body weight loss and colon shortening of 5-Fu treated mice. In addition, the fecal transplant from 5-Fu treated mice reduced body weight and colon length of vancomycin-pretreated mice. Taken together, our study demonstrated that gut microbiota was actively involved in the pathological process of 5-Fu induced intestinal mucositis, suggesting potential attenuation of 5-Fu induced intestinal mucositis by manipulating gut microbiota homeostasis.}, }
@article {pmid29123385, year = {2017}, author = {Asempa, TE and Nicolau, DP}, title = {Clostridium difficile infection in the elderly: an update on management.}, journal = {Clinical interventions in aging}, volume = {12}, number = {}, pages = {1799-1809}, pmid = {29123385}, issn = {1178-1998}, mesh = {Aged ; Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/therapeutic use ; Broadly Neutralizing Antibodies ; Clostridioides difficile ; Clostridium Infections/economics/epidemiology/*physiopathology/*therapy ; Fecal Microbiota Transplantation/methods ; Health Expenditures ; Humans ; Prospective Studies ; Recurrence ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; }, abstract = {The burden of Clostridium difficile infection (CDI) is profound and growing. CDI now represents a common cause of health care-associated diarrhea, and is associated with significant morbidity, mortality, and health care costs. CDI disproportionally affects the elderly, possibly explained by the following risk factors: age-related impairment of the immune system, increasing antibiotic utilization, and frequent health care exposure. In the USA, recent epidemiological studies estimate that two out of every three health care-associated CDIs occur in patients 65 years or older. Additionally, the elderly are at higher risk for recurrent CDI. Existing therapeutic options include metronidazole, oral vancomycin, and fidaxomicin. Choice of agent depends on disease severity, history of recurrence, and, increasingly, the drug cost. Bezlotoxumab, a recently approved monoclonal antibody targeting C. difficile toxin B, offers an exciting advancement into immunologic therapies. Similarly, fecal microbiota transplantation is gaining popularity as an effective option mainly for recurrent CDI. The challenge of decreasing CDI burden in the elderly involves adopting preventative strategies, optimizing initial treatment, and decreasing the risk of recurrence. Expanded strategies are certainly needed to improve outcomes in this high-risk population. This review considers available data from prospective and retrospective studies as well as case reports to illustrate the merits and gaps in care related to the management of CDI in the elderly.}, }
@article {pmid29122905, year = {2017}, author = {Philips, CA and Phadke, N and Ganesan, K and Augustine, P}, title = {Healthy donor faecal transplant for corticosteroid non-responsive severe alcoholic hepatitis.}, journal = {BMJ case reports}, volume = {2017}, number = {}, pages = {}, pmid = {29122905}, issn = {1757-790X}, mesh = {Adrenal Cortex Hormones/pharmacology ; Adult ; Drug Resistance ; Fecal Microbiota Transplantation/*methods ; Hepatitis, Alcoholic/diagnosis/*therapy ; Humans ; Liver Diseases, Alcoholic/*therapy ; Liver Transplantation ; Male ; Tissue Donors ; Treatment Outcome ; Waiting Lists ; }, abstract = {Patients with severe alcoholic hepatitis (SAH) have high mortality in the presence of steroid unresponsiveness in the absence of clear treatment recommendations. Liver transplantation is the curative option in such cases but is controversial in the wake of severe infections, post-transplant recidivism and long waiting on deceased donor listing. Animal and human studies have shed light on the beneficial effects of gut microbiota modulation in alcoholic liver disease. We present the first report of faecal microbiota transplantation (FMT) in a steroid non-responder in whom, clinical, biochemical and liver disease severity scores improved post-FMT and demonstrate distinct bacterial population changes pre-FMT and post-FMT. Healthy donor FMT could be safe and efficacious in SAH not responding to corticosteroid treatment, as a bridge to liver transplantation (LT) or in candidates who are unwilling or not ideal for LT for improvement in short-term transplant free survival. Larger controlled studies are required for confirmation.}, }
@article {pmid29114399, year = {2017}, author = {Kumar, R and Yi, N and Zhi, D and Eipers, P and Goldsmith, KT and Dixon, P and Crossman, DK and Crowley, MR and Lefkowitz, EJ and Rodriguez, JM and Morrow, CD}, title = {Erratum: Author Correction: Identification of donor microbe species that colonize and persist long term in the recipient after fecal transplant for recurrent Clostridium difficile.}, journal = {NPJ biofilms and microbiomes}, volume = {3}, number = {}, pages = {29}, doi = {10.1038/s41522-017-0037-y}, pmid = {29114399}, issn = {2055-5008}, abstract = {[This corrects the article DOI: 10.1038/s41522-017-0020-7.].}, }
@article {pmid29113028, year = {2018}, author = {García-Lezana, T and Raurell, I and Bravo, M and Torres-Arauz, M and Salcedo, MT and Santiago, A and Schoenenberger, A and Manichanh, C and Genescà, J and Martell, M and Augustin, S}, title = {Restoration of a healthy intestinal microbiota normalizes portal hypertension in a rat model of nonalcoholic steatohepatitis.}, journal = {Hepatology (Baltimore, Md.)}, volume = {67}, number = {4}, pages = {1485-1498}, doi = {10.1002/hep.29646}, pmid = {29113028}, issn = {1527-3350}, mesh = {Animals ; Disease Models, Animal ; Dysbiosis/*complications ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Hypertension, Portal/*etiology/microbiology ; Insulin Resistance ; Liver/pathology ; Male ; Non-alcoholic Fatty Liver Disease/*complications ; Rats ; Rats, Sprague-Dawley ; }, abstract = {UNLABELLED: Portal hypertension (PH) drives most of the clinical complications in chronic liver diseases. However, its progression in nonalcoholic steatohepatitis (NASH) and its association with the intestinal microbiota (IM) have been scarcely studied. Our aim was to investigate the role of the IM in the mechanisms leading to PH in early NASH. The experimental design was divided in two stages. In stage 1, Sprague-Dawley rats were fed for 8 weeks a high-fat, high-glucose/fructose diet (HFGFD) or a control diet/water (CD). Representative rats were selected as IM donors for stage 2. In stage 2, additional HFGFD and CD rats underwent intestinal decontamination, followed by IM transplantation with feces from opposite-diet donors (heterologous transplant) or autologous fecal transplant (as controls), generating four groups: CD-autotransplanted, CD-transplanted, HFGFD-autotransplanted, HFGFD-transplanted. After IM transplantation, the original diet was maintained for 12-14 days until death. HFGFD rats developed obesity, insulin resistance, NASH without fibrosis but with PH, intrahepatic endothelial dysfunction, and IM dysbiosis. In HFGFD rats, transplantation with feces from CD donors caused a significant reduction of PH to levels comparable to CD without significant changes in NASH histology. The reduction in PH was due to a 31% decrease of intrahepatic vascular resistance compared to the HFGFD-autotransplanted group (P < 0.05). This effect occurs through restoration of the sensitivity to insulin of the hepatic protein kinase B-dependent endothelial nitric oxide synthase signaling pathway.<br><br>CONCLUSION: The IM exerts a direct influence in the development of PH in rats with diet-induced NASH and dysbiosis; PH, insulin resistance, and endothelial dysfunction revert when a healthy IM is restored. (Hepatology 2018;67:1485-1498).}, }
@article {pmid29111440, year = {2018}, author = {Sargison, ND and Redman, E and Morrison, AA and Bartley, DJ and Jackson, F and Naghra-van Gijzel, H and Holroyd, N and Berriman, M and Cotton, JA and Gilleard, JS}, title = {A method for single pair mating in an obligate parasitic nematode.}, journal = {International journal for parasitology}, volume = {48}, number = {2}, pages = {159-165}, doi = {10.1016/j.ijpara.2017.08.010}, pmid = {29111440}, issn = {1879-0135}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; 206194//Wellcome Trust/United Kingdom ; 067811//Wellcome Trust/United Kingdom ; 230927//CIHR/Canada ; }, mesh = {Animals ; Crosses, Genetic ; DNA, Helminth ; Feces/parasitology ; Female ; *Genetic Variation ; Haemonchiasis/parasitology/*veterinary ; Haemonchus/*genetics ; Male ; Microsatellite Repeats ; Sheep ; Sheep Diseases/*parasitology ; }, abstract = {Parasitic nematode species have extremely high levels of genetic diversity, presenting a number of experimental challenges for genomic and genetic work. Consequently, there is a need to develop inbred laboratory strains with reduced levels of polymorphism. The most efficient approach to inbred line development is single pair mating, but this is challenging for obligate parasites where the adult sexual reproductive stages are inside the host, and thus difficult to experimentally manipulate. This paper describes a successful approach to single pair mating of a parasitic nematode, Haemonchus contortus. The method allows for polyandrous mating behaviour and involves the surgical transplantation of a single adult male worm with multiple immature adult females directly into the sheep abomasum. We used a panel of microsatellite markers to monitor and validate the single pair mating crosses and to ensure that the genotypes of progeny and subsequent filial generations were consistent with those expected from a mating between a single female parent of known genotype and a single male parent of unknown genotype. We have established two inbred lines that both show a significant overall reduction in genetic diversity based on microsatellite genotyping and genome-wide single nucleotide polymorphism. There was an approximately 50% reduction in heterozygous SNP sites across the genome in the MHco3.N1 line compared with the MoHco3(ISE) parental strain. The MHco3.N1 inbred line has subsequently been used to provide DNA template for whole genome sequencing of H. contortus. This work provides proof of concept and methodologies for forward genetic analysis of obligate parasitic nematodes.}, }
@article {pmid29110105, year = {2017}, author = {Clayton, JA and Toltzis, P}, title = {Recent Issues in Pediatric Clostridium difficile Infection.}, journal = {Current infectious disease reports}, volume = {19}, number = {12}, pages = {49}, pmid = {29110105}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: We focus on two recent aspects of Clostridium difficile infection (CDI) in children, namely the emergence of community-associated CDI (CA-CDI) and the incidence and prevention of recurrent CDI.<br><br>RECENT FINDINGS: Current surveys suggest that a large proportion of all pediatric CDI is acquired in the community. Risk factors and frequency estimates of pediatric CA-CDI, however, are confounded in babies and toddlers by a high rate of asymptomatic excretion, whose detection likely is exaggerated by the wide use of highly sensitive nucleic acid amplification tests. Recurrent diarrhea occurs in up to 25% of children with CDI. Preventative strategies for recurrent CDI in adults, namely pulse and taper antibiotic dosing, use of anti-CDI drugs with mild effect on the colonic microbiome, fecal microbiota transplantation, and passive immune therapy, currently are being tested in children. Future studies are required to better characterize community acquisition of CDI in children and to define the safety and effectiveness of preventative strategies for recurrent CDI.}, }
@article {pmid29107964, year = {2017}, author = {Lee, JC and Lee, HY and Kim, TK and Kim, MS and Park, YM and Kim, J and Park, K and Kweon, MN and Kim, SH and Bae, JW and Hur, KY and Lee, MS}, title = {Obesogenic diet-induced gut barrier dysfunction and pathobiont expansion aggravate experimental colitis.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0187515}, pmid = {29107964}, issn = {1932-6203}, mesh = {Animals ; Colitis/*pathology ; Diet, High-Fat/*adverse effects ; Intestinal Mucosa/microbiology/*physiopathology ; Mice ; Mice, Inbred C57BL ; Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD) inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease.}, }
@article {pmid29104169, year = {2018}, author = {Allegretti, JR and Allegretti, AS and Phelps, E and Xu, H and Kassam, Z and Fischer, M}, title = {Asymptomatic Clostridium difficile carriage rate post-fecal microbiota transplant is low: a prospective clinical and stool assessment.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {24}, number = {7}, pages = {780.e1-780.e3}, pmid = {29104169}, issn = {1469-0691}, support = {P30 DK034854/DK/NIDDK NIH HHS/United States ; }, mesh = {Carrier State/*microbiology ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*microbiology/*therapy ; Colonoscopy ; DNA, Bacterial/genetics ; Fecal Microbiota Transplantation/*statistics &amp; numerical data ; Feces/*microbiology ; Genes, Bacterial/genetics ; Humans ; Indiana ; Massachusetts ; Polymerase Chain Reaction ; Prospective Studies ; Recurrence ; Tertiary Care Centers ; Treatment Outcome ; }, abstract = {OBJECTIVES: We aimed to assess the asymptomatic Clostridium difficile carriage rates following fecal microbiota transplantation (FMT).<br><br>METHODS: All patients who underwent FMT for recurrent Clostridium difficile infection (CDI) via colonoscopy or sigmoidoscopy between June 2013 and April 2015 and had a minimum of 8-week follow-up post FMT at two tertiary care referral centres were included in the study. Patients were prospectively followed both clinically and with stool assessments for 8&#xa0;weeks post FMT. Assessments occurred at 1&#xa0;week and 4&#xa0;weeks post FMT to assess for failure. Failure was defined as presence of diarrhoeal symptoms and a positive CDI stool test by polymerase chain reaction for toxin gene (PCR) at any time point during the 8-week follow-up period. CDI stool testing using PCR was performed at weeks 1 and 4 post FMT in asymptomatic patients as well.<br><br>RESULTS: 167 patients were included. Twenty-eight patients (16.7% (28/167)) were FMT failures throughout the 8-week period. At week 1, seven patients had already failed the FMT. Of the remaining 160 patients, 144 were asymptomatic, and among these, 141 were negative for C.&#xa0;difficile toxin gene by PCR. This resulted in an asymptomatic carriage rate of 2.1% (3/144). At week 4, 143 patients had not yet failed FMT. Of these patients 129 patients were asymptomatic and among those, 125 were negative by PCR, resulting in an asymptomatic carriage rate of 3% (3/129).<br><br>CONCLUSIONS: Asymptomatic carriage after FMT is rare. This suggests that testing for cure after FMT in asymptomatic patients is not necessary.}, }
@article {pmid29104129, year = {2018}, author = {Allegretti, JR and Allegretti, AS and Phelps, E and Xu, H and Fischer, M and Kassam, Z}, title = {Classifying Fecal Microbiota Transplantation Failure: An Observational Study Examining Timing and Characteristics of Fecal Microbiota Transplantation Failures.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {16}, number = {11}, pages = {1832-1833}, doi = {10.1016/j.cgh.2017.10.031}, pmid = {29104129}, issn = {1542-7714}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Treatment Failure ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI), with cure rates higher than 80%.[1-3] FMT failure is defined as diarrhea and a positive stool laboratory test for C difficile at any point during the 8-week follow-up period after FMT.[4].}, }
@article {pmid29102616, year = {2018}, author = {Gini, A and Zauber, AG and Cenin, DR and Omidvari, AH and Hempstead, SE and Fink, AK and Lowenfels, AB and Lansdorp-Vogelaar, I}, title = {Cost Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.}, journal = {Gastroenterology}, volume = {154}, number = {3}, pages = {556-567.e18}, pmid = {29102616}, issn = {1528-0012}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; U01 CA115953/CA/NCI NIH HHS/United States ; U01 CA199335/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Clinical Decision-Making ; Colonoscopy/adverse effects/*economics ; Colorectal Neoplasms/complications/*diagnosis/*economics ; Computer Simulation ; Cost-Benefit Analysis ; Cystic Fibrosis/*complications/diagnosis/*economics/surgery ; Decision Support Techniques ; Early Detection of Cancer/adverse effects/*economics/methods ; Female ; *Health Care Costs ; Humans ; Life Expectancy ; Male ; Middle Aged ; Models, Economic ; Organ Transplantation/adverse effects/economics ; Predictive Value of Tests ; Quality-Adjusted Life Years ; Risk Assessment ; Risk Factors ; Stochastic Processes ; }, abstract = {BACKGROUND &amp; AIMS: Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared with the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis.<br><br>METHODS: We adjusted the existing Microsimulation Screening Analysis-Colon model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess if optimal screening strategies would change.<br><br>RESULTS: Colonoscopy every 5 years, starting at an age of 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in this population is not clear.<br><br>CONCLUSIONS: Using a Microsimulation Screening Analysis-Colon model, we found screening of patients with cystic fibrosis for CRC to be cost effective. Because of the higher risk of CRC in these patients, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis.}, }
@article {pmid29101931, year = {2017}, author = {Hefazi, M and Patnaik, MM and Hogan, WJ and Litzow, MR and Pardi, DS and Khanna, S}, title = {Safety and Efficacy of Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection in Patients With Cancer Treated With Cytotoxic Chemotherapy: A Single-Institution Retrospective Case Series.}, journal = {Mayo Clinic proceedings}, volume = {92}, number = {11}, pages = {1617-1624}, doi = {10.1016/j.mayocp.2017.08.016}, pmid = {29101931}, issn = {1942-5546}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Cytotoxins/*therapeutic use ; Enterocolitis, Pseudomembranous/complications/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasms/complications/*drug therapy ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: To study the safety and efficacy of fecal microbiota transplant (FMT) for Clostridium difficile infection (CDI) in patients with cancer treated with cytotoxic chemotherapy in a single-institution retrospective case series.<br><br>PATIENTS AND METHODS: Twenty-three consecutive patients with underlying hematologic (n=13) or solid (n=10) malignancies who underwent FMT for recurrent CDI from August 1, 2012, through June 30, 2016, were studied.<br><br>RESULTS: All the patients had received cytotoxic chemotherapy a median of 12 months (range, 1-340 months) before FMT. Patients had experienced a median of 4 (range, 2-9) CDI episodes and had been treated with a median of 106 days (range, 42-495 days) of vancomycin, metronidazole, or fidaxomicin before FMT. Twelve patients (52%) had severe/severe-complicated CDI at some stage. Eight patients (35%) had active cancer and 5 (22%) had received chemotherapy within 12 weeks of FMT. Diarrhea resolved without recurrence within 60 days of FMT in all but 3 patients (13%) (all had negative C difficile results). Of the 22 patients who were alive 60 days or more after FMT, 11 (48%) underwent further chemotherapy and 10 (43%) received more antibiotics. Two patients (9%) developed recurrent CDI 14 and 22 months after FMT. One death occurred 5 days after FMT as a result of cardiac arrest unrelated to FMT. There were no other severe adverse events and no infectious complications directly attributable to FMT.<br><br>CONCLUSION: This series demonstrates that FMT is a highly effective and safe therapeutic option for multiply recurrent CDI in patients with cancer treated with cytotoxic chemotherapy.}, }
@article {pmid29101192, year = {2018}, author = {Siegerstetter, SC and Petri, RM and Magowan, E and Lawlor, PG and Zebeli, Q and O'Connell, NE and Metzler-Zebeli, BU}, title = {Fecal Microbiota Transplant from Highly Feed-Efficient Donors Shows Little Effect on Age-Related Changes in Feed-Efficiency-Associated Fecal Microbiota from Chickens.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {2}, pages = {}, pmid = {29101192}, issn = {1098-5336}, mesh = {Age Factors ; Animal Feed ; Animals ; Bacteria/isolation &amp; purification ; Chickens/growth &amp; development/*microbiology ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Male ; Weight Gain ; }, abstract = {Chickens with good or poor feed efficiency (FE) have been shown to differ in their intestinal microbiota composition. This study investigated differences in the fecal bacterial community of highly and poorly feed-efficient chickens at 16 and 29 days posthatch (dph) and evaluated whether a fecal microbiota transplant (FMT) from feed-efficient donors early in life can affect the fecal microbiota in chickens at 16 and 29 dph and chicken FE and nutrient retention at 4 weeks of age. A total of 110 chickens were inoculated with a FMT or a control transplant (CT) on dph 1, 6, and 9 and ranked according to residual feed intake (RFI; the metric for FE) on 30 dph. Fifty-six chickens across both inoculation groups were selected as the extremes in RFI (29 low, 27 high). RFI-related fecal bacterial profiles were discernible at 16 and 29 dph. In particular, Lactobacillus salivarius, Lactobacillus crispatus, and Anaerobacterium operational taxonomic units were associated with low RFI (good FE). Multiple administrations of the FMT only slightly changed the fecal bacterial composition, which was supported by weighted UniFrac analysis, showing similar bacterial communities in the feces of both inoculation groups at 16 and 29 dph. Moreover, the FMT did not change the RFI and nutrient retention of highly and poorly feed-efficient recipients, whereas it tended to increase feed intake and body weight gain in female chickens. This finding suggests that host- and environment-related factors may more strongly affect chicken fecal microbiota and FE than the FMT.IMPORTANCE Modulating the chicken's early microbial colonization using a FMT from highly feed-efficient donor chickens may be a promising tool to establish a more desirable bacterial profile in recipient chickens, thereby improving host FE. Although FE-associated fecal bacterial profiles at 16 and 29 dph could be established, the microbiota composition of a FMT, when administered early in life, may not be a strong factor modulating the fecal microbiota at 2 to 4 weeks of life and reducing the variation in chicken's FE. Nevertheless, the present FMT may have potential benefits for growth performance in female chickens.}, }
@article {pmid29100842, year = {2018}, author = {Johnsen, PH and Hilpüsch, F and Cavanagh, JP and Leikanger, IS and Kolstad, C and Valle, PC and Goll, R}, title = {Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {3}, number = {1}, pages = {17-24}, doi = {10.1016/S2468-1253(17)30338-2}, pmid = {29100842}, issn = {2468-1253}, mesh = {Abdominal Pain/etiology ; Adult ; Double-Blind Method ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Humans ; Irritable Bowel Syndrome/physiopathology/*therapy ; Male ; Middle Aged ; Nausea/etiology ; Proof of Concept Study ; Vertigo/etiology ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a common condition characterised by abdominal pain, bloating, and poor quality of life. IBS might be caused by a gut dysbiosis. We aimed to compare faecal microbiota transplantation (FMT) with placebo in patients with IBS.<br><br>METHODS: In this double-blind, randomised, placebo-controlled, parallel-group, single-centre study, we enrolled patients with IBS with diarrhoea or with diarrhoea and constipation (excluding dominating constipation) defined by the ROME III criteria, scored as moderate to severe according to the IBS severity scoring system (IBS-SSS; a score of &#x2265;175). Eligible participants were aged 18-75 years and were recruited locally by general practitioners in northern Norway. We randomly assigned participants (2:1) in blocks of six to active or placebo FMT. Personnel not involved in the clinical performance of the trial generated the randomisation sequence using a randomisation website. Non-study personnel performed the final allocation and standardised the active and placebo transplants to make them identical in appearance and temperature. The faeces were freshly processed, and were used the same day (fresh transplant) or were stored in a freezer for later use (frozen transplant); participants' own faeces served as placebo. A dose of 8 mg loperamide was administered orally 2 h before endoscopy to retain the transplant. The transplant (50-80 g of faeces mixed with 200 mL of isotonic saline and 50 mL of 85% glycerol) was administered by a colonoscope to the caecum. The primary endpoint was symptom relief of more than 75 points assessed by IBS-SSS, 3 months after FMT. The primary analysis was done in the modified intention-to-treat population, excluding participants who did not undergo treatment or who were diagnosed with any other disease by pinch biopsies obtained during the treatment procedure. For the safety analysis, only participants who did not undergo treatment were excluded. The study is registered with ClinicalTrials.gov, number NCT02154867. The trial has been extended with an open-labelled study treating the placebo group with frozen FMT for further exploratory studies.<br><br>FINDINGS: Between Jan 1, and Oct 30, 2015, we recruited 90 participants and randomly assigned them to active treatment (n=60) or placebo (n=30). Three participants did not undergo FMT and four were excluded after diagnosis of microscopic colitis, leaving 83 for final modified intention-to-treat analysis (55 in the active treatment group and 28 in the placebo group). 36 (65%) of 55 participants receiving active treatment versus 12 (43%) of 28 receiving the placebo showed response at 3 months (p=0&#xb7;049). One participant had transient nausea and vertigo (active group) and was observed at the hospital for a few hours after the procedure. Two participants had soiling of transplant on their way home from treatment (one in each group) and three experienced self-limiting intermittent abdominal pain (one in the active group and two in the placebo group). No serious adverse events could be attributed to FMT.<br><br>INTERPRETATION: FMT induced significant symptom relief in patients with IBS. However, larger multicentre studies are needed to confirm the results.<br><br>FUNDING: HelseNord and the Norwegian Centre of Rural Medicine, University of Troms&#xf8;.}, }
@article {pmid29097871, year = {2017}, author = {Wang, WW and Zhang, Y and Huang, XB and You, N and Zheng, L and Li, J}, title = {Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction.}, journal = {World journal of gastroenterology}, volume = {23}, number = {38}, pages = {6983-6994}, pmid = {29097871}, issn = {2219-2840}, mesh = {Ammonia/blood ; Animals ; Carbon Tetrachloride Poisoning/complications ; *Fecal Microbiota Transplantation ; Hepatic Encephalopathy/blood/etiology/*prevention &amp; control ; Intestinal Mucosa/metabolism ; Male ; Memory ; Rats, Sprague-Dawley ; }, abstract = {AIM: To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl4)-induced acute hepatic dysfunction.<br><br>METHODS: A rat model of HE was established with CCl4. Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1&#x3b2;, IL-6 and tumor necrosis factor (TNF)-&#x3b1; was examined.<br><br>RESULTS: FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating pro-inflammatory factors such as interleukin (IL)-1&#x3b2;, IL-6 and tumor necrosis factor-&#x3b1; were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment.<br><br>CONCLUSION: FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.}, }
@article {pmid29097494, year = {2018}, author = {Routy, B and Le Chatelier, E and Derosa, L and Duong, CPM and Alou, MT and Daillère, R and Fluckiger, A and Messaoudene, M and Rauber, C and Roberti, MP and Fidelle, M and Flament, C and Poirier-Colame, V and Opolon, P and Klein, C and Iribarren, K and Mondragón, L and Jacquelot, N and Qu, B and Ferrere, G and Clémenson, C and Mezquita, L and Masip, JR and Naltet, C and Brosseau, S and Kaderbhai, C and Richard, C and Rizvi, H and Levenez, F and Galleron, N and Quinquis, B and Pons, N and Ryffel, B and Minard-Colin, V and Gonin, P and Soria, JC and Deutsch, E and Loriot, Y and Ghiringhelli, F and Zalcman, G and Goldwasser, F and Escudier, B and Hellmann, MD and Eggermont, A and Raoult, D and Albiges, L and Kroemer, G and Zitvogel, L}, title = {Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {91-97}, doi = {10.1126/science.aan3706}, pmid = {29097494}, issn = {1095-9203}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; CD4 Antigens/immunology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/genetics/*immunology ; Humans ; Immunotherapy/*methods ; Interleukin-12/immunology ; Metagenome/genetics ; Mice ; Neoplasms/*therapy ; Programmed Cell Death 1 Receptor/*antagonists &amp; inhibitors ; Receptors, CCR/immunology ; Receptors, CXCR3/immunology ; T-Lymphocytes/immunology ; Verrucomicrobia/genetics/immunology ; }, abstract = {Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clinical responses to ICIs and the relative abundance of Akkermansia muciniphila Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9[+]CXCR3[+]CD4[+] T lymphocytes into mouse tumor beds.}, }
@article {pmid29097493, year = {2018}, author = {Gopalakrishnan, V and Spencer, CN and Nezi, L and Reuben, A and Andrews, MC and Karpinets, TV and Prieto, PA and Vicente, D and Hoffman, K and Wei, SC and Cogdill, AP and Zhao, L and Hudgens, CW and Hutchinson, DS and Manzo, T and Petaccia de Macedo, M and Cotechini, T and Kumar, T and Chen, WS and Reddy, SM and Szczepaniak Sloane, R and Galloway-Pena, J and Jiang, H and Chen, PL and Shpall, EJ and Rezvani, K and Alousi, AM and Chemaly, RF and Shelburne, S and Vence, LM and Okhuysen, PC and Jensen, VB and Swennes, AG and McAllister, F and Marcelo Riquelme Sanchez, E and Zhang, Y and Le Chatelier, E and Zitvogel, L and Pons, N and Austin-Breneman, JL and Haydu, LE and Burton, EM and Gardner, JM and Sirmans, E and Hu, J and Lazar, AJ and Tsujikawa, T and Diab, A and Tawbi, H and Glitza, IC and Hwu, WJ and Patel, SP and Woodman, SE and Amaria, RN and Davies, MA and Gershenwald, JE and Hwu, P and Lee, JE and Zhang, J and Coussens, LM and Cooper, ZA and Futreal, PA and Daniel, CR and Ajami, NJ and Petrosino, JF and Tetzlaff, MT and Sharma, P and Allison, JP and Jenq, RR and Wargo, JA}, title = {Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {97-103}, pmid = {29097493}, issn = {1095-9203}, support = {R25 CA056452/CA/NCI NIH HHS/United States ; UL1 TR000128/TR/NCATS NIH HHS/United States ; K12 CA088084/CA/NCI NIH HHS/United States ; K08 CA160692/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; R25 CA057730/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/*immunology ; Humans ; *Immunotherapy ; Melanoma/immunology/*therapy ; Metagenome ; Mice ; Programmed Cell Death 1 Receptor/*antagonists &amp; inhibitors ; Skin Neoplasms/immunology/*therapy ; }, abstract = {Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.}, }
@article {pmid29097439, year = {2018}, author = {Riva, A and Patel, V and Kurioka, A and Jeffery, HC and Wright, G and Tarff, S and Shawcross, D and Ryan, JM and Evans, A and Azarian, S and Bajaj, JS and Fagan, A and Patel, V and Mehta, K and Lopez, C and Simonova, M and Katzarov, K and Hadzhiolova, T and Pavlova, S and Wendon, JA and Oo, YH and Klenerman, P and Williams, R and Chokshi, S}, title = {Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease.}, journal = {Gut}, volume = {67}, number = {5}, pages = {918-930}, pmid = {29097439}, issn = {1468-3288}, support = {109965/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Cell Culture Techniques ; Cytokines/metabolism ; Ethanol/*adverse effects ; Feces/microbiology ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Intestinal Mucosa/*immunology/microbiology ; Liver Diseases, Alcoholic/*immunology/metabolism/microbiology ; Male ; Middle Aged ; Mucosal-Associated Invariant T Cells/immunology/*metabolism/physiology ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND/AIMS: Intestinal permeability with systemic distribution of bacterial products are central in the immunopathogenesis of alcoholic liver disease (ALD), yet links with intestinal immunity remain elusive. Mucosa-associated invariant T cells (MAIT) are found in liver, blood and intestinal mucosa and are a key component of antibacterial host defences. Their role in ALD is unknown.<br><br>METHODS/DESIGN: We analysed frequency, phenotype, transcriptional regulation and function of blood MAIT cells in severe alcoholic hepatitis (SAH), alcohol-related cirrhosis (ARC) and healthy controls (HC). We also examined direct impact of ethanol, bacterial products from faecal extracts and antigenic hyperstimulation on MAIT cell functionality. Presence of MAIT cells in colon and liver was assessed by quantitative PCR and immunohistochemistry/gene expression respectively.<br><br>RESULTS: In ARC and SAH, blood MAIT cells were dramatically depleted, hyperactivated and displayed defective antibacterial cytokine/cytotoxic responses. These correlated with suppression of lineage-specific transcription factors and hyperexpression of homing receptors in the liver with intrahepatic preservation of MAIT cells in ALD. These alterations were stronger in SAH, where surrogate markers of bacterial infection and microbial translocation were higher than ARC. Ethanol exposure in vitro, in vivo alcohol withdrawal and treatment with Escherichia coli had no effect on MAIT cell frequencies, whereas exposure to faecal bacteria/antigens induced functional impairments comparable with blood MAIT cells from ALD and significant MAIT cell depletion, which was not observed in other T cell compartments.<br><br>CONCLUSIONS: In ALD, the antibacterial potency of MAIT cells is compromised as a consequence of contact with microbial products and microbiota, suggesting that the 'leaky' gut observed in ALD drives MAIT cell dysfunction and susceptibility to infection in these patients.}, }
@article {pmid29093626, year = {2017}, author = {Lahtinen, P and Mattila, E and Anttila, VJ and Tillonen, J and Teittinen, M and Nevalainen, P and Salminen, S and Satokari, R and Arkkila, P}, title = {Faecal microbiota transplantation in patients with Clostridium difficile and significant comorbidities as well as in patients with new indications: A case series.}, journal = {World journal of gastroenterology}, volume = {23}, number = {39}, pages = {7174-7184}, pmid = {29093626}, issn = {2219-2840}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*pathogenicity ; Coinfection ; Comorbidity ; Drug Resistance, Bacterial ; Enterocolitis, Pseudomembranous/diagnosis/immunology/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces/*microbiology ; Female ; Humans ; Immunocompromised Host ; Male ; Middle Aged ; Recurrence ; Risk Factors ; Treatment Outcome ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is effective in recurrent Clostridium difficile infection (rCDI). Knowledge of the safety and efficacy of FMT treatment in immune deficient patients is scarce. FMT has been suggested as a potential method for an increasing number of new indications besides rCDI. Among our FMT-treated rCDI patients, we reviewed those with major comorbidities: two human immunodeficiency virus patients, six haemodialysis patients, two kidney transplant patients, two liver transplant patients and a patient with chronic lymphatic leukaemia. We also reviewed those treated with FMT for indications other than rCDI: Salmonella carriage (two patients), trimethylaminuria (two patients), small intestinal bacterial overgrowth (SIBO; one patient), and lymphocytic colitis (one patient), as well as a common variable immunodeficiency patient with chronic norovirus infection and ESBL-producing Escherichia coli (E. coli) carriage. Of the thirteen rCDI patients treated with FMT, eleven cleared the CDI. The observed adverse events were not directly attributable to FMT. Concerning the special indications, both Salmonellas and ESBL-producing E. coli were eradicated. One trimethylaminuria patient and one SIBO-patient reported a reduction of symptoms. Three patients did not experience a benefit from FMT: chronic norovirus, lymphocytic colitis and the other fish malodour syndrome. There were no reported side effects in this group. FMT appeared to be safe and effective for immunocompromised patients with rCDI. FMT showed promise for the eradication of antibiotic-resistant bacteria, but further research is warranted.}, }
@article {pmid29086331, year = {2018}, author = {Benezech, A and Desmazes-Dufeu, N and Baumstarck, K and Bouvier, M and Coltey, B and Reynaud-Gaubert, M and Vitton, V}, title = {Prevalence of Fecal Incontinence in Adults with Cystic Fibrosis.}, journal = {Digestive diseases and sciences}, volume = {63}, number = {4}, pages = {982-988}, pmid = {29086331}, issn = {1573-2568}, mesh = {Adult ; Age Factors ; Cystic Fibrosis/*complications ; Fecal Incontinence/*epidemiology ; Female ; Health Status ; Humans ; Male ; Prevalence ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Surveys and Questionnaires ; Urinary Incontinence/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Patients with cystic fibrosis (CF) are deemed at risk of developing urinary incontinence (UI) due to repeated coughing and other factors causing increased pressure on the pelvic floor. Fecal incontinence (FI) is probably derived from the same mechanism, but only very few data are available on its frequency.<br><br>AIMS: The aim of this study was to determine the prevalence of FI in an adult population with CF.<br><br>METHODS: This retrospective study was conducted from January 2012 to June 2014. Patients were recruited from Marseille referral center for adult CF. They were asked to fill in a self-completed anonymous questionnaire for symptom assessment of UI and FI. Clinical data and a detailed history of CF were also recorded.<br><br>RESULTS: A total of 155 out of 190 patients (92 females) of mean age 30.5&#xa0;&#xb1;&#xa0;11&#xa0;years completed the survey. Seventy-three patients (47%) were lung transplanted. Forty patients (25.8%) reported FI with a mean St Mark's score of 4.9&#xa0;&#xb1;&#xa0;2. Thirty-five patients (22.6%) reported UI. Eighteen patients (11.6%) reported both FI and UI. FI was significantly more frequent in older patients (34.27 vs. 29.54&#xa0;years, p&#xa0;=&#xa0;0.03) and in patients with associated UI (p&#xa0;=&#xa0;0.001). No relationship was found between respiratory, bacterial, nutritional status, transplantation, pancreatic status, practice of physiotherapy, delivery history, and FI.<br><br>CONCLUSIONS: The high prevalence of FI in CF and its negative impacts need to integrate this symptom in the overall treatment of this pathology. The systematic early detection of FI may allow its rapid management and limit their consequences.}, }
@article {pmid29084766, year = {2018}, author = {Chen, S and Li, X and Liu, L and Liu, C and Han, X}, title = {Ophiopogonin D alleviates high-fat diet-induced metabolic syndrome and changes the structure of gut microbiota in mice.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {32}, number = {3}, pages = {1139-1153}, doi = {10.1096/fj.201700741RR}, pmid = {29084766}, issn = {1530-6860}, mesh = {Animals ; Body Weight ; Diet, High-Fat ; Dysbiosis/etiology/pathology/*prevention &amp; control ; Gastrointestinal Microbiome/*drug effects ; Hyperglycemia/etiology/pathology/*prevention &amp; control ; Hyperlipidemias/etiology/pathology/*prevention &amp; control ; Insulin Resistance ; Male ; Metabolic Syndrome/etiology/pathology/*prevention &amp; control ; Mice ; Mice, Inbred C57BL ; Saponins/*pharmacology ; Spirostans/*pharmacology ; }, abstract = {Gut dysbiosis is believed to play a critical role in the pathogenesis of metabolic diseases, including obesity. Ophiopogonin D (OP-D), a steroidal glycoside and an active component extracted from the root of the plant Ophiopogon japonicus (also known as radix ophiopogonis), can regulate multiple physiologic processes. Here we show that OP-D administration reduces body weight, hyperglycemia, hyperlipidemia, and insulin resistance in male mice fed a high-fat diet (HFD). Pyrosequencing of the V4 regions of 16S rRNA genes in mouse feces revealed a deviation of the gut microbiota in response to OP-D treatment. In particular, the decreased Firmicutes-to- Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels indicated that OP-D reversed HFD-induced gut dysbiosis. More importantly, the effects of OP-D on modulation of obesity and microbiota were transferable via horizontal feces transfer from OP-D-treated mice to HFD-fed mice. Taken together, our results suggest that OP-D may be used as a prebiotic agent to treat obesity-associated gut dysbiosis and metabolic syndrome.-Chen, S., Li, X., Liu, L., Liu, C., Han, X. Ophiopogonin D alleviates high-fat diet-induced metabolic syndrome and changes the structure of gut microbiota in mice.}, }
@article {pmid29084074, year = {2018}, author = {Kvasnovsky, CL and Leong, LEX and Choo, JM and Abell, GCJ and Papagrigoriadis, S and Bruce, KD and Rogers, GB}, title = {Clinical and symptom scores are significantly correlated with fecal microbiota features in patients with symptomatic uncomplicated diverticular disease: a pilot study.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {30}, number = {1}, pages = {107-112}, doi = {10.1097/MEG.0000000000000995}, pmid = {29084074}, issn = {1473-5687}, mesh = {Abdominal Pain/microbiology ; Aged ; Aged, 80 and over ; Bacteria/classification/genetics/*isolation &amp; purification ; Colon/*microbiology ; Diverticulitis, Colonic/complications/diagnosis/*microbiology ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Pain Measurement ; Pilot Projects ; Prognosis ; Ribotyping ; Risk Factors ; Severity of Illness Index ; }, abstract = {BACKGROUND: There is growing consensus that symptomatic uncomplicated diverticular disease is a chronic inflammatory condition, and that alterations in the fecal microbiota may contribute to its pathogenesis.<br><br>OBJECTIVE: The aim of this study was to relate the fecal microbiota composition in symptomatic uncomplicated diverticular disease to measures of inflammation, symptoms, and history of previous acute diverticulitis.<br><br>PARTICIPANTS AND METHODS: Fecal microbiota composition in 28 individuals with symptomatic uncomplicated diverticular disease was characterized by 16S RNA gene amplicon sequencing. Microbiota composition was related to clinical history, symptom and inflammation measures, and demographic variables.<br><br>RESULTS: Previous acute diverticulitis was associated with higher relative abundance of Pseudobutyrivibrio, Bifidobacterium, Christensenellaceae family, and Mollicutes RF9 order (P=0.004, 0.006, 0.010, and 0.019, respectively), but not microbiota alpha or beta diversity. A higher bloating severity score was significantly correlated with a higher relative abundance of Ruminococcus (P=0.032), and significantly inversely correlated with the relative abundance of the Roseburia (P=0.002). Fecal calprotectin levels were positively correlated with alpha diversity (Shannon index, P=0.005) and the relative abundance of Lactobacillus (P=0.004). Pain score was positively correlated with the relative abundance of Cyanobacterium (adjusted P=0.032).<br><br>CONCLUSION: Patient symptoms in symptomatic diverticular disease are significantly correlated with features of the fecal microbiota. Our findings suggest the potential utility of therapies that target intestinal microbiology, such as dietary prebiotic supplements.}, }
@article {pmid29083037, year = {2018}, author = {Woodhouse, CA and Patel, VC and Singanayagam, A and Shawcross, DL}, title = {Review article: the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {47}, number = {2}, pages = {192-202}, doi = {10.1111/apt.14397}, pmid = {29083037}, issn = {1365-2036}, support = {PB-PG-0215-36070/DH_/Department of Health/United Kingdom ; }, mesh = {Animals ; Dysbiosis/*complications/microbiology/therapy ; End Stage Liver Disease/*etiology/microbiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestinal Mucosa/metabolism ; Intestines/microbiology ; Liver Cirrhosis/etiology/microbiology/therapy ; Non-alcoholic Fatty Liver Disease/etiology/microbiology/therapy ; Probiotics/therapeutic use ; }, abstract = {BACKGROUND: Mortality from chronic liver disease is rising exponentially. The liver is intimately linked to the gut via the portal vein, and exposure to gut microbiota and their metabolites translocating across the gut lumen may impact upon both the healthy and diseased liver. Modulation of gut microbiota could prove to be a potential therapeutic target.<br><br>AIM: To characterise the changes in the gut microbiome that occur in chronic liver disease and to assess the impact of manipulation of the microbiome on the liver.<br><br>METHODS: We conducted a PubMed search using search terms including 'microbiome', 'liver' and 'cirrhosis' as well as 'non-alcoholic fatty liver disease', 'steatohepatitis', 'alcohol' and 'primary sclerosing cholangitis'. Relevant articles were also selected from references of articles and review of the ClinicalTrials.gov website.<br><br>RESULTS: Reduced bacterial diversity, alcohol sensitivity and the development of gut dysbiosis are seen in several chronic liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease and primary sclerosing cholangitis. Perturbations in gut commensals could lead to deficient priming of the immune system predisposing the development of immune-mediated diseases. Furthermore, transfer of stool from an animal with the metabolic syndrome may induce steatosis in a healthy counterpart. Patients with cirrhosis develop dysbiosis, small bowel bacterial overgrowth and increased gut wall permeability, allowing bacterial translocation and uptake of endotoxin inducing hepatic and systemic inflammation.<br><br>CONCLUSIONS: Manipulation of the gut microbiota with diet, probiotics or faecal microbiota transplantation to promote the growth of "healthy" bacteria may ameliorate the dysbiosis and alter prognosis.}, }
@article {pmid29080338, year = {2017}, author = {Wang, HH and Garruti, G and Liu, M and Portincasa, P and Wang, DQ}, title = {Cholesterol and Lipoprotein Metabolism and Atherosclerosis: Recent Advances In reverse Cholesterol Transport.}, journal = {Annals of hepatology}, volume = {16}, number = {Suppl. 1: s3-105.}, pages = {s27-s42}, doi = {10.5604/01.3001.0010.5495}, pmid = {29080338}, issn = {1665-2681}, mesh = {Animals ; Anticholesteremic Agents/therapeutic use ; Atherosclerosis/blood/epidemiology/*metabolism/prevention &amp; control ; Biological Transport ; Cholesterol, HDL/blood/*metabolism ; Cholesterol, LDL/blood/*metabolism ; Humans ; Hypercholesterolemia/blood/drug therapy/epidemiology/*metabolism ; Intestinal Mucosa/*metabolism ; Intestines/drug effects ; Liver/drug effects/*metabolism ; Prognosis ; Risk Factors ; }, abstract = {Atherosclerosis is characterized by lipid accumulation, inflammatory response, cell death and fibrosis in the arterial wall, and is major pathological basis for ischemic coronary heart disease (CHD), which is the leading cause of morbidity and mortality in the USA and Europe. Intervention studies with statins have shown to reduce LDL cholesterol levels and subsequently the risk of developing CHD. However, not all the aggressive statin therapy could decrease the risk of developing CHD. Many clinical and epidemiological studies have clearly demonstrated that the HDL cholesterol is inversely associated with risk of CHD and is a critical and independent component of predicting its risk. Elucidations of HDL metabolism give rise to therapeutic targets with potential to raising plasma HDL cholesterol levels, thereby reducing the risk of developing CHD. The concept of reverse cholesterol transport is based on the hypothesis that HDL displays an cardioprotective function, which is a process involved in the removal of excess cholesterol that is accumulated in the peripheral tissues (e.g., macrophages in the aortae) by HDL, transporting it to the liver for excretion into the feces via the bile. In this review, we summarize the latest advances in the role of the lymphatic route in reverse cholesterol transport, as well as the biliary and the non-biliary pathways for removal of cholesterol from the body. These studies will greatly increase the likelihood of discovering new lipid-lowering drugs, which are more effective in the prevention and therapeutic intervention of CHD that is the major cause of human death and disability worldwide.}, }
@article {pmid29080336, year = {2017}, author = {Di Ciaula, A and Garruti, G and Lunardi Baccetto, R and Molina-Molina, E and Bonfrate, L and Wang, DQ and Portincasa, P}, title = {Bile Acid Physiology.}, journal = {Annals of hepatology}, volume = {16}, number = {Suppl. 1: s3-105.}, pages = {s4-s14}, doi = {10.5604/01.3001.0010.5493}, pmid = {29080336}, issn = {1665-2681}, mesh = {Animals ; Bacteria/metabolism ; Bile Acids and Salts/*metabolism ; Energy Metabolism ; Enterohepatic Circulation ; Feces/chemistry ; Gallbladder/*metabolism ; Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/*metabolism ; Intestines/microbiology ; Lipid Metabolism ; Liver/*metabolism ; Signal Transduction ; }, abstract = {The primary bile acids (BAs) are synthetized from colesterol in the liver, conjugated to glycine or taurine to increase their solubility, secreted into bile, concentrated in the gallbladder during fasting, and expelled in the intestine in response to dietary fat, as well as bio-transformed in the colon to the secondary BAs by the gut microbiota, reabsorbed in the ileum and colon back to the liver, and minimally lost in the feces. BAs in the intestine not only regulate the digestion and absorption of cholesterol, triglycerides, and fat-soluble vitamins, but also play a key role as signaling molecules in modulating epithelial cell proliferation, gene expression, and lipid and glucose metabolism by activating farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor-1 (GPBAR-1, also known as TGR5) in the liver, intestine, muscle and brown adipose tissue. Recent studies have revealed the metabolic pathways of FXR and GPBAR-1 involved in the biosynthesis and enterohepatic circulation of BAs and their functions as signaling molecules on lipid and glucose metabolism.}, }
@article {pmid29079158, year = {2017}, author = {Donskey, CJ}, title = {Clostridium difficile in Older Adults.}, journal = {Infectious disease clinics of North America}, volume = {31}, number = {4}, pages = {743-756}, doi = {10.1016/j.idc.2017.07.003}, pmid = {29079158}, issn = {1557-9824}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/epidemiology/*microbiology/*pathology/therapy ; Feces/microbiology ; Humans ; Infection Control/methods ; *Nursing Homes ; }, abstract = {Recent increases in the incidence of Clostridium difficile infection (CDI) have been observed in all age groups, but the elderly have been disproportionately affected and long-term care facilities (LTCFs) have borne a significant proportion of the increasing burden. Recurrences are common in older adults and may have significant adverse effects on quality of life. Ensuring appropriate diagnostic testing and management is challenging for older adults in the community and in LTCFs. This review focuses on current concepts related to the epidemiology, diagnosis, and management of CDI in older adults.}, }
@article {pmid29077649, year = {2017}, author = {Wine, E and Griffiths, AM}, title = {Fecal Microbial Transplantation for Pediatric Ulcerative Colitis: Are We There Yet?.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000001811}, pmid = {29077649}, issn = {1536-4801}, }
@article {pmid29076444, year = {2017}, author = {van Beurden, YH and Terveer, EM and Keller, JJ and Kuijper, EJ and Mulder, CJJ and Vandenbroucke-Grauls, CMJE}, title = {[Faecal microbiota transplantation: indications in perspective].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {161}, number = {}, pages = {D1623}, pmid = {29076444}, issn = {1876-8784}, mesh = {Clostridium Infections/complications ; Colitis, Ulcerative/*microbiology/*therapy ; Crohn Disease/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; }, abstract = {- As yet, with cure rates around 85%, recurrent Clostridium difficile infection is the only definite indication for faecal microbiota transplantation.- Faecal microbiota transplantation induces clinical remission and endoscopic improvements in 24-30% of patients with ulcerative colitis, compared to 5% (water) to 20% (autologous faeces) in placebo-treated patients. Current research focuses on the identification of 'super donors', and subgroups of patients in which faecal microbiota transplantation is effective.- In patients with metabolic syndrome, faecal microbiota transplantation may increase insulin sensitivity. Weight, body mass index, and energy metabolism are not affected by faecal microbiota transplantation in humans.- In addition to the aforementioned indications, faecal microbiota transplantation is an emerging treatment modality for patients with Crohn's disease, irritable bowel syndrome, graft-versus-host-disease, and carriage of multidrug-resistant micro-organisms. Randomized controlled trials, comparing faecal microbiota transplantation with placebo treatment, are required to determine the effectiveness of faecal microbiota transplantation in these patient groups.}, }
@article {pmid29076071, year = {2017}, author = {Yoon, S and Yu, J and McDowell, A and Kim, SH and You, HJ and Ko, G}, title = {Bile salt hydrolase-mediated inhibitory effect of Bacteroides ovatus on growth of Clostridium difficile.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {55}, number = {11}, pages = {892-899}, pmid = {29076071}, issn = {1976-3794}, mesh = {Antibiosis ; Bacteroides/*enzymology/metabolism ; Bile Acids and Salts/chemistry/*metabolism/pharmacology ; Clostridioides difficile/*drug effects/*growth &amp; development ; Clostridium Infections/microbiology/therapy ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Hydrolases/*metabolism ; }, abstract = {Clostridium difficile infection (CDI) is one of the most common nosocomial infections. Dysbiosis of the gut microbiota due to consumption of antibiotics is a major contributor to CDI. Recently, fecal microbiota transplantation (FMT) has been applied to treat CDI. However, FMT has important limitations including uncontrolled exposure to pathogens and standardization issues. Therefore, it is necessary to evaluate alternative treatment methods, such as bacteriotherapy, as well as the mechanism through which beneficial bacteria inhibit the growth of C. difficile. Here, we report bile acid-mediated inhibition of C. difficile by Bacteroides strains which can produce bile salt hydrolase (BSH). Bacteroides strains are not commonly used to treat CDI; however, as they comprise a large proportion of the intestinal microbiota, they can contribute to bile acid-mediated inhibition of C. difficile. The inhibitory effect on C. difficile growth increased with increasing bile acid concentration in the presence of Bacteroides ovatus SNUG 40239. Furthermore, this inhibitory effect on C. difficile growth was significantly attenuated when bile acid availability was reduced by cholestyramine, a bile acid sequestrant. The findings of this study are important due to the discovery of a new bacterial strain that in the presence of available bile acids inhibits growth of C. difficile. These results will facilitate development of novel bacteriotherapy strategies to control CDI.}, }
@article {pmid29071710, year = {2018}, author = {Khanna, S}, title = {Microbiota Replacement Therapies: Innovation in Gastrointestinal Care.}, journal = {Clinical pharmacology and therapeutics}, volume = {103}, number = {1}, pages = {102-111}, doi = {10.1002/cpt.923}, pmid = {29071710}, issn = {1532-6535}, mesh = {Biological Therapy/methods ; Clostridium Infections/physiopathology/*therapy ; Drug Resistance, Multiple/immunology ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Immune System Diseases/physiopathology/*therapy ; Inflammation/immunology/*therapy ; Treatment Outcome ; }, abstract = {There has been an increasing interest in the association between human disease and altered gut microbiota, and therapeutics to modulate microbiota to treat disease. Healthy human gastrointestinal microbiota is highly diverse and rich, and harbors between 500 and 2,000 species. Diseases associated with dysbiotic microbiota include antibiotic-associated diarrhea, Clostridium difficile infection, multidrug-resistant organisms, inflammatory bowel disease, obesity, metabolic syndrome, diabetes mellitus, neuropsychiatric diseases, and systemic autoimmune diseases. Microbiota replacement therapies have shown immense promise in treatment of recurrent C. difficile infection and are being studied for other indications. Microbiota replacement therapies for indications other than C. difficile infection should be performed only in research settings. There is an immense need for standardized microbiota replacement therapies for C. difficile infection. Studies are needed to elucidate long-term safety and adverse events from these therapies.}, }
@article {pmid29071167, year = {2017}, author = {Liu, T and Yang, Z and Zhang, X and Han, N and Yuan, J and Cheng, Y}, title = {16S rDNA analysis of the effect of fecal microbiota transplantation on pulmonary and intestinal flora.}, journal = {3 Biotech}, volume = {7}, number = {6}, pages = {370}, pmid = {29071167}, issn = {2190-572X}, abstract = {This study aims to explore the effect of FMT on regulations of dysbacteriosis of pulmonary and intestinal flora in rats with 16S rDNA sequencing technology. A total of 27 SPF rats (3-4 weeks old) were randomly divided into three groups: normal control group (K), model control group (MX), and fecal microbiota transplantation group (FMT); each group contained nine rats. The OTU values of the pulmonary and intestinal flora of the MX group decreased significantly compared with the normal control group. After FMT, the OTU value of pulmonary flora increased, while the value of OTU in intestinal flora declined. At the phylum level, FMT down-regulated Proteobacteria, Firmicutes, and Bacteroidetes in the pulmonary flora. At the genus level, FMT down-regulated Pseudomonas, Sphingobium, Lactobacillus, Rhizobium, and Acinetobacter, thus maintaining the balance of the pulmonary flora. Moreover, FMT could change the structure and diversity of the pulmonary and intestinal flora by positively regulating the pulmonary flora and negatively regulating intestinal flora. This study may provide a scientific basis for FMT treatment of respiratory diseases.}, }
@article {pmid29067223, year = {2017}, author = {Arbel, LT and Hsu, E and McNally, K}, title = {Cost-Effectiveness of Fecal Microbiota Transplantation in the Treatment of Recurrent Clostridium Difficile Infection: A Literature Review.}, journal = {Cureus}, volume = {9}, number = {8}, pages = {e1599}, pmid = {29067223}, issn = {2168-8184}, abstract = {Clostridium difficile (C. difficile) is a common cause of antibiotic--associated diarrhea (AAD), being responsible for 15--25% of all AAD cases. The purpose of this literature review is to determine the cost-effectiveness of fecal microbiota transplantation (FMT) and how it compares in this regard to the standard treatments of choice for recurrent C. difficile infection (CDI). The review of the literature along with the evaluation of three comparative cost effective analyses yielded findings consistent with the view that FMT is the most cost-effective option in treating recurrent CDI. There are some (but considerably less) data indicating that FMT may be a cost effective strategy in treating initial CDI, as well. The superior cost-effectiveness of FMT as compared to the preferred standards of treatment for recurrent CDI suggest FMT use should become more integrated in routine clinical practice. Increased utilization of FMTs would allow for better control of this increasingly problematic disease as well as lower costs associated with its management.}, }
@article {pmid29066578, year = {2017}, author = {Hayase, E and Hashimoto, D and Nakamura, K and Noizat, C and Ogasawara, R and Takahashi, S and Ohigashi, H and Yokoi, Y and Sugimoto, R and Matsuoka, S and Ara, T and Yokoyama, E and Yamakawa, T and Ebata, K and Kondo, T and Hiramine, R and Aizawa, T and Ogura, Y and Hayashi, T and Mori, H and Kurokawa, K and Tomizuka, K and Ayabe, T and Teshima, T}, title = {R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease.}, journal = {The Journal of experimental medicine}, volume = {214}, number = {12}, pages = {3507-3518}, pmid = {29066578}, issn = {1540-9538}, mesh = {Administration, Oral ; Animals ; Bacteria/metabolism ; Cell Differentiation/drug effects ; Cytoprotection/drug effects ; Dysbiosis/*etiology/pathology/*prevention &amp; control ; Female ; Graft vs Host Disease/*complications/pathology ; Humans ; Intestines/pathology ; Mice, Inbred C57BL ; Paneth Cells/drug effects/metabolism/*pathology ; Recombinant Proteins/administration &amp; dosage/pharmacology/therapeutic use ; Stem Cell Transplantation ; Stem Cells/drug effects/metabolism ; Thrombospondins/*pharmacology/*therapeutic use ; alpha-Defensins/metabolism ; }, abstract = {The intestinal microbial ecosystem is actively regulated by Paneth cell-derived antimicrobial peptides such as α-defensins. Various disorders, including graft-versus-host disease (GVHD), disrupt Paneth cell functions, resulting in unfavorably altered intestinal microbiota (dysbiosis), which further accelerates the underlying diseases. Current strategies to restore the gut ecosystem are bacteriotherapy such as fecal microbiota transplantation and probiotics, and no physiological approach has been developed so far. In this study, we demonstrate a novel approach to restore gut microbial ecology by Wnt agonist R-Spondin1 (R-Spo1) or recombinant α-defensin in mice. R-Spo1 stimulates intestinal stem cells to differentiate to Paneth cells and enhances luminal secretion of α-defensins. Administration of R-Spo1 or recombinant α-defensin prevents GVHD-mediated dysbiosis, thus representing a novel and physiological approach at modifying the gut ecosystem to restore intestinal homeostasis and host-microbiota cross talk toward therapeutic benefits.}, }
@article {pmid29066574, year = {2018}, author = {Conceição-Neto, N and Deboutte, W and Dierckx, T and Machiels, K and Wang, J and Yinda, KC and Maes, P and Van Ranst, M and Joossens, M and Raes, J and Vermeire, S and Matthijnssens, J}, title = {Low eukaryotic viral richness is associated with faecal microbiota transplantation success in patients with UC.}, journal = {Gut}, volume = {67}, number = {8}, pages = {1558-1559}, pmid = {29066574}, issn = {1468-3288}, mesh = {Colitis, Ulcerative ; *Eukaryota ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid29056925, year = {2017}, author = {Fabbiano, S and Suárez-Zamorano, N and Trajkovski, M}, title = {Host-Microbiota Mutualism in Metabolic Diseases.}, journal = {Frontiers in endocrinology}, volume = {8}, number = {}, pages = {267}, pmid = {29056925}, issn = {1664-2392}, support = {336607/ERC_/European Research Council/International ; }, abstract = {The intestinal microbiota is a plastic ecosystem that is shaped by environmental and genetic factors, interacting with virtually all tissues of the host. Many signals result from the interplay between the microbiota with its mammalian symbiont that can lead to altered metabolism. Disruptions in the microbial composition are associated with a number of comorbidities linked to the metabolic syndrome. Promoting the niche expansion of beneficial bacteria through diet and supplements can improve metabolic disorders. Reintroducing bacteria through probiotic treatment or fecal transplant is a strategy under active investigation for multiple pathological conditions. Here, we review the recent knowledge of microbiota's contribution to host pathology, the modulation of the microbiota by dietary habits, and the potential therapeutic benefits of reshaping the gut bacterial landscape in context of metabolic disorders such as obesity.}, }
@article {pmid29052237, year = {2018}, author = {Kump, P and Wurm, P and Gröchenig, HP and Wenzl, H and Petritsch, W and Halwachs, B and Wagner, M and Stadlbauer, V and Eherer, A and Hoffmann, KM and Deutschmann, A and Reicht, G and Reiter, L and Slawitsch, P and Gorkiewicz, G and Högenauer, C}, title = {The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {47}, number = {1}, pages = {67-77}, pmid = {29052237}, issn = {1365-2036}, mesh = {Adult ; Anti-Bacterial Agents/administration &amp; dosage ; Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Male ; Microbiota ; Middle Aged ; Prospective Studies ; Remission Induction ; Ruminococcus ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Faecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown.<br><br>AIMS: To establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success.<br><br>METHODS: This is an open controlled trial of repeated faecal microbiota transplantation after antibiotic pre-treatment (FMT-group, n&#xa0;=&#xa0;17) vs antibiotic pre-treatment only (AB-group, n&#xa0;=&#xa0;10) in 27 therapy refractory ulcerative colitis patients over 90&#xa0;days. Faecal samples of donors and patients were analysed by 16SrRNA gene-based microbiota analysis.<br><br>RESULTS: In the FMT-group, 10/17 (59%) of patients showed a response and 4/17 (24%) a remission to faecal microbiota transplantation. Response to faecal microbiota transplantation was mainly influenced by the taxonomic composition of the donor's microbiota. Stool of donors with a high bacterial richness (observed species remission 946&#xa0;&#xb1;&#xa0;93 vs no response 797&#xa0;&#xb1;&#xa0;181 at 15367&#xa0;rps) and a high relative abundance of Akkermansia muciniphila (3.3&#xa0;&#xb1;&#xa0;3.1% vs 0.1&#xa0;&#xb1;&#xa0;0.2%), unclassified Ruminococcaceae (13.8&#xa0;&#xb1;&#xa0;5.0% vs 7.5&#xa0;&#xb1;&#xa0;3.7%), and Ruminococcus spp. (4.9&#xa0;&#xb1;&#xa0;3.5% vs 1.0&#xa0;&#xb1;&#xa0;0.7%) were more likely to induce remission. In contrast antibiotic treatment alone (AB-group) was poorly tolerated, probably because of a sustained decrease of intestinal microbial richness.<br><br>CONCLUSIONS: The taxonomic composition of the donor's intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in ulcerative colitis patients. The design of specific microbial preparation might lead to new treatments for ulcerative colitis.}, }
@article {pmid29052181, year = {2017}, author = {Hampe, CS and Roth, CL}, title = {Probiotic strains and mechanistic insights for the treatment of type 2 diabetes.}, journal = {Endocrine}, volume = {58}, number = {2}, pages = {207-227}, pmid = {29052181}, issn = {1559-0100}, support = {R01 DK026190/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Bifidobacterium ; Diabetes Mellitus, Type 2/*drug therapy/microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intestines/*microbiology ; *Lactobacillus ; *Probiotics ; }, abstract = {INTRODUCTION: The intestinal microbial composition appears to differ between healthy controls and individuals with Type 2 diabetes (T2D). This observation has led to the hypothesis that perturbations of the intestinal microbiota may contribute to the development of T2D. Manipulations of the intestinal microbiota may therefore provide a novel approach in the prevention and treatment of T2D. Indeed, fecal transplants have shown promising results in both animal models for obesity and T2D and in human clinical trials. To avoid possible complications associated with fecal transplants, probiotics are considered as a viable alternative therapy. An important, however often underappreciated, characteristic of probiotics is that individual strains may have different, even opposing, effects on the host. This strain specificity exists also within the same species. A comprehensive understanding of the underlying mechanisms at the strain level is therefore crucial for the selection of suitable probiotic strains.<br><br>PURPOSE: The aim of this review is to discuss the mechanisms employed by specific probiotic strains of the Lactobacillus and the Bifidobacterium genuses, which showed efficacy in the treatment of obesity and T2D. Some probiotic strains employ recurring beneficial effects, including the production of anti-microbial lactic acid, while other strains display highly unique features, such as hydrolysis of tannins.<br><br>CONCLUSION: A major obstacle in the evaluation of probiotic strains lays in the great number of strains, differences in detection methodology and measured outcome parameters. The understanding of further research should be directed towards the development of standardized evaluation methods to facilitate the comparison of different studies.}, }
@article {pmid29045252, year = {2018}, author = {Bandera, A and De Benedetto, I and Bozzi, G and Gori, A}, title = {Altered gut microbiome composition in HIV infection: causes, effects and potential intervention.}, journal = {Current opinion in HIV and AIDS}, volume = {13}, number = {1}, pages = {73-80}, doi = {10.1097/COH.0000000000000429}, pmid = {29045252}, issn = {1746-6318}, mesh = {Anti-HIV Agents/therapeutic use ; Bacterial Translocation ; *Dysbiosis ; *Gastrointestinal Microbiome ; HIV Infections/*complications/drug therapy/*pathology ; *Host-Pathogen Interactions ; Humans ; Inflammation/pathology ; Lymphocyte Activation ; *Microbiota ; }, abstract = {PURPOSE OF REVIEW: Aim of this review is to summarize the alterations occurring in gut microbiome composition after HIV infection, and to underline how intestinal dysbiosis can affect immune homeostasis, immune recovery, and persisting immune activation under antiretroviral therapy (ART). Many interventions have been suggested, mostly with inconclusive results.<br><br>RECENT FINDINGS: Recent evidence showed that gut microbiota from HIV-infected patients harbor reproducible differences compared to uninfected individuals. In this line, there is growing evidence that alterations in gut ecology during HIV infection correlate with persistence of immune defects and chronic inflammation. A reduced microbial diversity in feces of HIV-infected patients is highly associated with microbial translocation and monocyte activation markers; moreover, changes in mucosa-associated bacteria correlate with inflammation and T-cell activation.<br><br>SUMMARY: Studying the human host-microbiota interaction suggests that the consequences of HIV infection on microbial composition can influence immune status in HIV patients. ART induces microbiome changes that are independent of HIV infection, and some imply that ART may enhance dysbiosis. Studies and trials evaluated the effects of administering probiotics and prebiotics, finding a potential benefit on inflammation markers and immune cell activation. Emerging data on fecal microbial transplantation need to be assessed with further studies.}, }
@article {pmid29040661, year = {2018}, author = {Bluestone, H and Kronman, MP and Suskind, DL}, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {7}, number = {1}, pages = {e6-e8}, doi = {10.1093/jpids/pix076}, pmid = {29040661}, issn = {2048-7207}, mesh = {Child ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/etiology/*therapy ; DiGeorge Syndrome/therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunocompromised Host ; Leukemia, Myeloid, Acute/therapy ; Male ; Mucopolysaccharidosis I/therapy ; Recurrence ; }, }
@article {pmid29039256, year = {2017}, author = {Woodworth, MH and Sitchenko, KL and Carpentieri, C and Friedman-Moraco, RJ and Wang, T and Kraft, CS}, title = {Ethical Considerations in Microbial Therapeutic Clinical Trials.}, journal = {The New bioethics : a multidisciplinary journal of biotechnology and the body}, volume = {23}, number = {3}, pages = {210-218}, pmid = {29039256}, issn = {2050-2885}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; }, mesh = {Clinical Trials as Topic/*ethics ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*ethics ; Gastrointestinal Microbiome ; Humans ; }, abstract = {As understanding of the human microbiome improves, novel therapeutic targets to improve human health with microbial therapeutics will continue to expand. We outline key considerations of balancing risks and benefits, optimising access, returning key results to research participants, and potential conflicts of interest.}, }
@article {pmid29039142, year = {2017}, author = {Quigley, EMM}, title = {Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.}, journal = {Current neurology and neuroscience reports}, volume = {17}, number = {12}, pages = {94}, pmid = {29039142}, issn = {1534-6293}, mesh = {Animals ; Brain/*drug effects/*physiopathology ; Gastrointestinal Microbiome/*drug effects/*physiology ; Humans ; *Molecular Targeted Therapy ; Neurodegenerative Diseases/*drug therapy/*physiopathology ; }, abstract = {PURPOSE OF REVIEW: The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies.<br><br>RECENT FINDINGS: Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.}, }
@article {pmid29035948, year = {2018}, author = {Desai, SN and Landay, AL}, title = {HIV and aging: role of the microbiome.}, journal = {Current opinion in HIV and AIDS}, volume = {13}, number = {1}, pages = {22-27}, doi = {10.1097/COH.0000000000000433}, pmid = {29035948}, issn = {1746-6318}, mesh = {Aging/*pathology ; Biological Therapy/methods ; Dysbiosis/pathology ; Gastrointestinal Microbiome/*immunology ; HIV Infections/complications/*pathology ; Humans ; Microbiota/*immunology ; }, abstract = {PURPOSE OF REVIEW: The purpose of this article is to review age-associated alterations in microbiota composition, diversity and functional features in context of immune senescence, chronic inflammation and comorbidities associated with HIV infection. The overall goal is to assess whether modulating the microbiome will likely improve resilience of the immune system and augment return to health.<br><br>RECENT FINDINGS: Alteration in the gut microbiota composition diversity and function occur in HIV and aging. Importantly, butyrate producing bacteria are reduced in both HIV and aging individuals. There is increasing relevance of studying metabolomics in the context of HIV-associated non-AIDS comorbidities and aging. Interventional prospects of probiotics, prebiotics and fecal microbiota transplantation in HIV and aging will provide novel therapeutic approaches.<br><br>SUMMARY: Increasing evidence suggests a significant link in changes in the composition, diversity and functional aspects of intestinal microbiome with normal aging and HIV infection. Data on association of metabolites produced by the microbiome with HIV-associated non-AIDS comorbidities is mounting. The impact of the microbiome alterations on inflammation, immune and organ senescence and mechanisms by which bio-behavioral pathways will exacerbate these outcomes needs to be further evaluated.}, }
@article {pmid29034981, year = {2018}, author = {McIlroy, J and Ianiro, G and Mukhopadhya, I and Hansen, R and Hold, GL}, title = {Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {47}, number = {1}, pages = {26-42}, doi = {10.1111/apt.14384}, pmid = {29034981}, issn = {1365-2036}, mesh = {Colitis, Ulcerative/diagnosis/*therapy ; Crohn Disease/diagnosis/*therapy ; Diet ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Microbiota ; Recurrence ; }, abstract = {BACKGROUND: The concept of an altered collective gut microbiota rather than identification of a single culprit is possibly the most significant development in inflammatory bowel disease research. We have entered the "omics" era, which now allows us to undertake large-scale/high-throughput microbiota analysis which may well define how we approach diagnosis and treatment of inflammatory bowel disease (IBD) in the future, with a strong steer towards personalised therapeutics.<br><br>AIM: To assess current epidemiological, experimental and clinical evidence of the current status of knowledge relating to the gut microbiome, and its role in IBD, with emphasis on reviewing the evidence relating to microbial therapeutics and future microbiome modulating therapeutics.<br><br>METHODS: A Medline search including items 'intestinal microbiota/microbiome', 'inflammatory bowel disease', 'ulcerative colitis', 'Crohn's disease', 'faecal microbial transplantation', 'dietary manipulation' was performed.<br><br>RESULTS: Disease remission and relapse are associated with microbial changes in both mucosal and luminal samples. In particular, a loss of species richness in Crohn's disease has been widely observed. Existing therapeutic approaches broadly fall into 3 categories, namely: accession, reduction or indirect modulation of the microbiome. In terms of microbial therapeutics, faecal microbial transplantation appears to hold the most promise; however, differences in study design/methodology mean it is currently challenging to elegantly translate results into clinical practice.<br><br>CONCLUSIONS: Existing approaches to modulate the gut microbiome are relatively unrefined. Looking forward, the future of microbiome-modulating therapeutics looks bright with several novel strategies/technologies on the horizon. Taken collectively, it is clear that ignoring the microbiome in IBD is not an option.}, }
@article {pmid29033923, year = {2017}, author = {El Hage, R and Hernandez-Sanabria, E and Van de Wiele, T}, title = {Emerging Trends in "Smart Probiotics": Functional Consideration for the Development of Novel Health and Industrial Applications.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1889}, pmid = {29033923}, issn = {1664-302X}, abstract = {The link between gut microbiota and human health is well-recognized and described. This ultimate impact on the host has contributed to explain the mutual dependence between humans and their gut bacteria. Gut microbiota can be manipulated through passive or active strategies. The former includes diet, lifestyle, and environment, while the latter comprise antibiotics, pre- and probiotics. Historically, conventional probiotic strategies included a phylogenetically limited diversity of bacteria and some yeast strains. However, biotherapeutic strategies evolved in the last years with the advent of fecal microbiota transplant (FMT), successfully applied for treating CDI, IBD, and other diseases. Despite the positive outcomes, long-term effects resulting from the uncharacterized nature of FMT are not sufficiently studied. Thus, developing strategies to simulate the FMT, using characterized gut colonizers with identified phylogenetic diversity, may be a promising alternative. As the definition of probiotics states that the microorganism should have beneficial effects on the host, several bacterial species with proven efficacy have been considered next generation probiotics. Non-conventional candidate strains include Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis, and members of the Clostridia clusters IV, XIVa, and XVIII. However, viable intestinal delivery is one of the current challenges, due to their stringent survival conditions. In this review, we will cover current perspectives on the development and assessment of next generation probiotics and the approaches that industry and stakeholders must consider for a successful outcome.}, }
@article {pmid29030396, year = {2018}, author = {Speck, PG and Mitchell, JG}, title = {Faecal microbiota transplantation donor stools need screening for poliovirus.}, journal = {Gut}, volume = {67}, number = {8}, pages = {1559-1560}, doi = {10.1136/gutjnl-2017-314356}, pmid = {29030396}, issn = {1468-3288}, mesh = {Clostridioides difficile ; Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; *Poliovirus ; }, }
@article {pmid29026601, year = {2017}, author = {van Beurden, YH and de Groot, PF and van Nood, E and Nieuwdorp, M and Keller, JJ and Goorhuis, A}, title = {Complications, effectiveness, and long term follow-up of fecal microbiota transfer by nasoduodenal tube for treatment of recurrent Clostridium difficile infection.}, journal = {United European gastroenterology journal}, volume = {5}, number = {6}, pages = {868-879}, pmid = {29026601}, issn = {2050-6406}, abstract = {BACKGROUND: Fecal microbiota transfer (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI), but data on procedure-related complications and long-term outcome are scarce.<br><br>METHODS: All patients treated with FMT for recurrent CDI at the Academic Medical Center between July 2010 and January 2016 were included. FMT was performed according to the FECAL trial protocol: administration of fresh donor feces (related or unrelated donor) through a duodenal tube after pre-treatment with vancomycin and bowel lavage. We collected information on FMT-related complications, recurrent CDI, and short- and long-term adverse events by telephone interviews using a structured questionnaire at three months after FMT, and at the time of data collection of this study.<br><br>RESULTS: In total, 39 patients were treated with FMT. The primary cure rate (no recurrence &#x2264;8 weeks after one infusion with donor feces) was 82% (32 of 39 patients). Of the seven patients with recurrent CDI after FMT, four were cured by antibiotic therapy alone (fidaxomicin in three patients, metronidazole in one patient) and three by repeat FMT. Peri-procedural complications occurred in five patients, comprising fecal regurgitation or vomiting. One patient died one week post-FMT due to pneumonia; a causal relation with FMT could not be excluded. The follow-up period ranged between 3 and 68 months. No long-term side effects were reported.<br><br>CONCLUSIONS: Our data underline the efficacy of FMT as treatment for recurrent CDI. Importantly, it is possible to cure post-FMT recurrences with antibiotic therapy alone. Peri-procedural complications do occur and should be closely monitored to help identify high-risk patients. To minimize the risk of complications, all FMT candidates should be evaluated to assess the most ideal delivery method.}, }
@article {pmid29026445, year = {2017}, author = {Aggarwala, V and Liang, G and Bushman, FD}, title = {Viral communities of the human gut: metagenomic analysis of composition and dynamics.}, journal = {Mobile DNA}, volume = {8}, number = {}, pages = {12}, pmid = {29026445}, issn = {1759-8753}, support = {P30 AI045008/AI/NIAID NIH HHS/United States ; R01 AI082020/AI/NIAID NIH HHS/United States ; R01 HL113252/HL/NHLBI NIH HHS/United States ; U54 HL117798/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND: The numerically most abundant biological entities on Earth are viruses. Vast populations prey on the cellular microbiota in all habitats, including the human gut.<br><br>MAIN BODY: Here we review approaches for studying the human virome, and some recent results on movement of viral sequences between bacterial cells and eukaryotic hosts. We first overview biochemical and bioinformatic methods, emphasizing that specific choices in the methods used can have strong effects on the results obtained. We then review studies characterizing the virome of the healthy human gut, which reveal that most of the viruses detected are typically uncharacterized phage - the viral dark matter - and that viruses that infect human cells are encountered only rarely. We then review movement of phage between bacterial cells during antibiotic treatment. Here a radical proposal for extensive movement of antibiotic genes on phage has been challenged by a careful reanalysis of the metagenomic annotation methods used. We then review two recent studies of movement of whole phage communities between human individuals during fecal microbial transplantation, which emphasize the possible role of lysogeny in dispersal.<br><br>SHORT CONCLUSION: Methods for studying the human gut virome are improving, yielding interesting data on movement of phage genes between cells and mammalian host organisms. However, viral populations are vast, and studies of their composition and function are just beginning.}, }
@article {pmid29020346, year = {2018}, author = {Khanna, S and Tariq, R and Tosh, PK and Walker, RC and Razonable, RR and Pardi, DS}, title = {Reply to Davido et al.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {3}, pages = {483-485}, doi = {10.1093/cid/cix789}, pmid = {29020346}, issn = {1537-6591}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Urinary Tract Infections ; }, }
@article {pmid29020328, year = {2018}, author = {Hocquart, M and Lagier, JC and Cassir, N and Saidani, N and Eldin, C and Kerbaj, J and Delord, M and Valles, C and Brouqui, P and Raoult, D and Million, M}, title = {Early Fecal Microbiota Transplantation Improves Survival in Severe Clostridium difficile Infections.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {5}, pages = {645-650}, doi = {10.1093/cid/cix762}, pmid = {29020328}, issn = {1537-6591}, mesh = {Aged ; Aged, 80 and over ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/mortality/*therapy ; Enterocolitis, Pseudomembranous ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; France ; Hospitalization/statistics &amp; numerical data ; Humans ; Male ; Odds Ratio ; Recurrence ; Retrospective Studies ; Ribotyping ; Severity of Illness Index ; Survival Analysis ; *Time-to-Treatment ; Treatment Outcome ; }, abstract = {BACKGROUND: Severe Clostridium difficile infections (CDIs) are associated with a high mortality rate despite medical and/or surgical treatment. Fecal microbiota transplantation (FMT) prevents recurrences, but its effect on survival has been shown only in patients with O27 ribotype CDI. Here, we investigated whether early FMT could improve survival in hospitalized CDI patients, particularly those with severe infection.<br><br>METHODS: We performed a retrospective cohort study between May 2013 and April 2016 at the infectious diseases department of the North University Hospital of Marseille, France. Patients received either medical treatment alone or treatment with early FMT. The primary outcome was the 3-month mortality rate.<br><br>RESULTS: A total of 111 patients were included: 66 in the FMT group and 45 in the non-FMT group. No patient underwent surgery. The O27 ribotype (odds ratio [OR], 3.64 [95% confidence interval {CI}, 1.05- 12.6], P = .04), severe CDI (OR, 9.62 [95% CI, 2.16-42.8], P = .003), and FMT (OR, 0.13 [95% CI, .04-.44], P = .001) were independent predictors of 3-month mortality. FMT improved survival in severe cases (OR, 0.08 [95% CI, .016-.34], P = .001) but not in nonsevere cases (OR, 1.07 [95% CI, .02-56.3], P = .97), independent of age, sex, comorbidities (Charlson score), and ribotype. The number of severe patients who needed to be treated to save 1 life at 3 months was 2.<br><br>CONCLUSIONS: Early FMT dramatically reduces mortality and should be proposed as a first-line treatment for severe CDI. Further studies are needed to clarify complications and contraindications. Surgery should be reassessed in this context.}, }
@article {pmid29020255, year = {2018}, author = {Orenstein, R and King, K and Patron, RL and DiBaise, JK and Etzioni, D}, title = {Mini-Fecal Microbiota Transplantation for Treatment of Clostridium difficile Proctitis Following Total Colectomy.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {2}, pages = {299-300}, doi = {10.1093/cid/cix736}, pmid = {29020255}, issn = {1537-6591}, mesh = {Aged ; Clostridium Infections/*surgery/*therapy ; *Colectomy ; Fecal Microbiota Transplantation/*methods ; Humans ; Male ; Postoperative Complications/*therapy ; Proctitis/*therapy ; Treatment Outcome ; }, abstract = {Rarely, in fulminant Clostridium difficile infection (CDI), the rectal stump is persistently infected following total abdominal colectomy. We report cure of a septic patient with proctitis by fecal microbiota transplant via rectal swabs (mini-FMT). This novel procedure offers a management option for recurrent CDI following total abdominal colectomy.}, }
@article {pmid29020240, year = {2018}, author = {Andremont, A}, title = {Too Early to Recommend Early Fecal Microbiota Transplantation in Patients With Severe Clostridium difficile Infection, or Not Too Early?.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {5}, pages = {651-652}, doi = {10.1093/cid/cix763}, pmid = {29020240}, issn = {1537-6591}, mesh = {*Clostridium Infections ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid29020225, year = {2018}, author = {Davido, B and Dinh, A and Deconinck, L and de Truchis, P}, title = {Fecal Microbiota Transplantation and Urinary Tract Infection: An Interesting Approach.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {3}, pages = {483}, doi = {10.1093/cid/cix788}, pmid = {29020225}, issn = {1537-6591}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Urinary Tract Infections ; }, }
@article {pmid29020222, year = {2018}, author = {Leung, V and Vincent, C and Edens, TJ and Miller, M and Manges, AR}, title = {Antimicrobial Resistance Gene Acquisition and Depletion Following Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {3}, pages = {456-457}, pmid = {29020222}, issn = {1537-6591}, mesh = {Anti-Bacterial Agents/pharmacology ; Clostridium Infections/*therapy ; Drug Resistance, Multiple, Bacterial/*genetics ; Fecal Microbiota Transplantation/*adverse effects ; Feces/microbiology ; *Gastrointestinal Microbiome ; Genes, Bacterial ; *Genes, MDR ; High-Throughput Nucleotide Sequencing ; Humans ; Recurrence ; }, abstract = {Fecal microbiota transplantation (FMT) may be a novel approach to eliminate multidrug-resistant bacteria from the gut and to prevent future infections. Using whole metagenome sequencing data from 8 FMT donor-recipient pairs, we identified 37 and 95 antimicrobial resistance genes that were acquired by or removed from FMT recipients, respectively.}, }
@article {pmid29020210, year = {2017}, author = {Tariq, R and Pardi, DS and Tosh, PK and Walker, RC and Razonable, RR and Khanna, S}, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection Reduces Recurrent Urinary Tract Infection Frequency.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {10}, pages = {1745-1747}, doi = {10.1093/cid/cix618}, pmid = {29020210}, issn = {1537-6591}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Clostridioides difficile/drug effects ; Clostridium Infections/complications/drug therapy/*epidemiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Recurrence ; Retrospective Studies ; Urinary Tract Infections/*complications/*epidemiology ; }, abstract = {Broad-spectrum antibiotics for recurrent multidrug-resistant urinary tract infections (UTIs) disrupt the gut microbiome and promote antibiotic resistance. Fecal microbiota transplantation led to resolution of recurrent Clostridium difficile, significantly decreased recurrent UTI frequency, and improved antibiotic susceptibility profile of UTI-causing organisms.}, }
@article {pmid29020185, year = {2017}, author = {Golob, JL and Pergam, SA and Srinivasan, S and Fiedler, TL and Liu, C and Garcia, K and Mielcarek, M and Ko, D and Aker, S and Marquis, S and Loeffelholz, T and Plantinga, A and Wu, MC and Celustka, K and Morrison, A and Woodfield, M and Fredricks, DN}, title = {Stool Microbiota at Neutrophil Recovery Is Predictive for Severe Acute Graft vs Host Disease After Hematopoietic Cell Transplantation.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {12}, pages = {1984-1991}, pmid = {29020185}, issn = {1537-6591}, support = {R01 AI134808/AI/NIAID NIH HHS/United States ; T32 AI007044/AI/NIAID NIH HHS/United States ; T32 AI118690/AI/NIAID NIH HHS/United States ; }, mesh = {Actinobacteria/genetics/isolation &amp; purification ; Adult ; Aged ; Bacteria/classification/genetics/isolation &amp; purification ; Feces/*microbiology ; Female ; Firmicutes/genetics/isolation &amp; purification ; *Gastrointestinal Microbiome ; Graft vs Host Disease/complications/*diagnosis/immunology/*microbiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Neutrophils/*immunology ; Polymerase Chain Reaction ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Graft-versus-host disease (GVHD) is common after allogeneic hematopoietic cell transplantation (HCT). Risk for death from GVHD has been associated with low bacterial diversity in the stool microbiota early after transplant; however, the specific species associated with GVHD risk remain poorly defined.<br><br>METHODS: We prospectively collected serial weekly stool samples from 66 patients who underwent HCT, starting pre-transplantation and continuing weekly until 100 days post-transplant, a total of 694 observations in HCT recipients. We used 16S rRNA gene polymerase chain reaction with degenerate primers, followed by high-throughput sequencing to assess the relative abundance of sequence reads from bacterial taxa in stool samples over time.<br><br>RESULTS: The gut microbiota was highly dynamic in HCT recipients, with loss and appearance of taxa common on short time scales. As in prior studies, GVHD was associated with lower alpha diversity of the stool microbiota. At neutrophil recovery post-HCT, the presence of oral Actinobacteria and oral Firmicutes in stool was positively correlated with subsequent GVHD; Lachnospiraceae were negatively correlated. A gradient of bacterial species (difference of the sum of the relative abundance of positive correlates minus the sum of the relative abundance of negative correlates) was most predictive (receiver operator characteristic area under the curve of 0.83) of subsequent severe acute GVHD.<br><br>CONCLUSIONS: The stool microbiota around the time of neutrophil recovery post-HCT is predictive of subsequent development of severe acute GVHD in this study.}, }
@article {pmid29020157, year = {2018}, author = {Allegretti, JR and Kao, D and Sitko, J and Fischer, M and Kassam, Z}, title = {Early Antibiotic Use After Fecal Microbiota Transplantation Increases Risk of Treatment Failure.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {1}, pages = {134-135}, doi = {10.1093/cid/cix684}, pmid = {29020157}, issn = {1537-6591}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Assessment ; Time Factors ; Treatment Failure ; }, abstract = {Antibiotic use within the first 8 weeks after fecal microbiota transplantation (FMT) may disrupt microbial engraftment and limit FMT effectiveness. We aimed to assess the burden of antibiotic use within 8 weeks of FMT and its impact on FMT efficacy.}, }
@article {pmid28993208, year = {2018}, author = {Li, S and Lv, J and Li, J and Zhao, Z and Guo, H and Zhang, Y and Cheng, S and Sun, J and Pan, H and Fan, S and Li, Z}, title = {Intestinal microbiota impact sepsis associated encephalopathy via the vagus nerve.}, journal = {Neuroscience letters}, volume = {662}, number = {}, pages = {98-104}, doi = {10.1016/j.neulet.2017.10.008}, pmid = {28993208}, issn = {1872-7972}, mesh = {Animals ; Cerebral Cortex/metabolism/pathology ; Cytokines/metabolism ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Hippocampus/metabolism ; Lipopolysaccharides/pharmacology ; Male ; Memory ; Microglia/metabolism ; Rats, Sprague-Dawley ; Sepsis-Associated Encephalopathy/*microbiology/*physiopathology/psychology ; Spatial Learning ; Vagus Nerve/microbiology/*physiopathology ; }, abstract = {OBJECTIVE: The pathogenesis of sepsis associated encephalopathy (SAE) remains poorly understood. Vagus nerve plays an important role in gut-microbiota-brain axis. This study aimed to investigate whether vague nerve is a key mediator of the impact of intestinal microbiota on SAE.<br><br>METHODS: Male rats were randomly divided into four groups (n=20): SHAM (SH) group, lipopolysaccharide (LPS) group, fecal microbiota transplantation (FMT) +LPS group, and vagotomy (VGX)+LPS+FMT group. The left cervical vagotomy was performed 30min before LPS administration in LPS+FMT+VGX group. LPS+ FMT and LPS+FMT+VGX groups received nasogastric infusion of feces from healthy donor three times a day. Fecal samples were collected every two days to monitor changes in microbiota composition by 16S rDNA analysis. Brain function was evaluated by behavioral tests and EEG. The levels of tumor necrosis factor alpha (TNF-&#x3b1;), interleukin (IL)-1&#x3b2;, IL-6, IL-10 in brain cortex were detected by ELISA. The expression of Iba-1 in brain cortex was assessed by immunohistochemistry and Western blot analysis.<br><br>RESULTS: Significant modification of microbiota composition, characterized by a profound increase of commensals in the Firmicutes phylum and depletion of opportunistic organisms in the Proteobacteria phylum, was observed in FMT groups compared to LPS group. Furthermore, we identified a reconstituted bacterial community enriched in Firmicutes and depleted of Proteobacteria. In both FMT groups the diversity of the fecal microbiota and the microbiota composition were similar to SH group. LPS mice treated with FMT demonstrated a better spatial memory and less EEG abnormalities, significantly attenuated levels of IL-1&#x3b2;, IL-6, TNF-&#x3b1;, and decreased number of Iba-1 positive microglia in the cortex, but these beneficial effects of FMT were reversed by VGX.<br><br>CONCLUSIONS: FMT can change intestinal microbiota in sepsis patients, and vagus nerve is a key mediator between intestinal microbiota and SAE. These findings suggest that FMT and vagus nerve are potential therapy targets for treating SAE.}, }
@article {pmid28991839, year = {2018}, author = {Michail, S}, title = {Fecal Microbial Transplant In Children With Ulcerative Colitis: A Randomized, Double-Blinded, Placebo-Controlled Pilot Study: Retracted.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000001772}, pmid = {28991839}, issn = {1536-4801}, }
@article {pmid28990516, year = {2018}, author = {Okubo, H and Nakatsu, Y and Kushiyama, A and Yamamotoya, T and Matsunaga, Y and Inoue, MK and Fujishiro, M and Sakoda, H and Ohno, H and Yoneda, M and Ono, H and Asano, T}, title = {Gut Microbiota as a Therapeutic Target for Metabolic Disorders.}, journal = {Current medicinal chemistry}, volume = {25}, number = {9}, pages = {984-1001}, doi = {10.2174/0929867324666171009121702}, pmid = {28990516}, issn = {1875-533X}, mesh = {Animals ; Diabetes Mellitus, Type 2/*microbiology/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Molecular Targeted Therapy ; Non-alcoholic Fatty Liver Disease/drug therapy/*microbiology/*therapy ; Obesity/*microbiology/*therapy ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {BACKGROUND: Gut microbiota play a vital role not only in the digestion and absorption of nutrients, but also in homeostatic maintenance of host immunity, metabolism and the gut barrier. Recent evidence suggests that gut microbiota alterations contribute to the pathogenesis of metabolic disorders.<br><br>OBJECTIVE AND METHOD: In this review, we discuss the association between the gut microbiota and metabolic disorders, such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease, and the contribution of relevant modulating interventions, focusing on recent human studies.<br><br>RESULTS: Several studies have identified potential causal associations between gut microbiota and metabolic disorders, as well as the underlying mechanisms. The effects of modulating interventions, such as prebiotics, probiotics, fecal microbiota transplantation, and other new treatment possibilities on these metabolic disorders have also been reported.<br><br>CONCLUSION: A growing body of evidence highlights the role of gut microbiota in the development of dysbiosis, which in turn influences host metabolism and disease phenotypes. Further studies are required to elucidate the precise mechanisms by which gut microbiota-derived mediators induce metabolic disorders and modulating interventions exert their beneficial effects in humans. The gut microbiota represents a novel potential therapeutic target for a range of metabolic disorders.}, }
@article {pmid28989593, year = {2017}, author = {Hamzehzadeh, L and Yousefi, M and Ghaffari, SH}, title = {Colorectal Cancer Screening: A Comprehensive Review to Recent Non-Invasive Methods.}, journal = {International journal of hematology-oncology and stem cell research}, volume = {11}, number = {3}, pages = {250-261}, pmid = {28989593}, issn = {2008-3009}, abstract = {Colorectal cancer (CRC) is one of the most common cancers worldwide and considered to be one of the hassles in medical communities. CRC develops from precancerous polyps in the colon or rectum and is preventable and curable by an early diagnosis and with the removal of premalignant polyps. In recent years, scientists have looked for inexpensive and safe ways to detect CRC in its earliest stages. Strong evidence shows that screening for CRC is a crucial way to reduce the incidence and mortality of this devastating disease. The main purpose for screening is to detect cancer or pre-cancer signs in all asymptomatic patients. In this review, we holistically introduce major pathways involved in the initiation and progression of colorectal tumorgenesis, which mainly includes chromosome instability (CIN), microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), and we then will discuss different screening tests and especially the latest non-invasive fecal screening test kits for the detection of CRC.}, }
@article {pmid28987073, year = {2017}, author = {Ejtahed, HS and Hasani-Ranjbar, S and Larijani, B}, title = {Human Microbiome as an Approach to Personalized Medicine.}, journal = {Alternative therapies in health and medicine}, volume = {23}, number = {6}, pages = {8-9}, pmid = {28987073}, issn = {1078-6791}, mesh = {Biodiversity ; Humans ; Microbiology/trends ; *Microbiota ; Pharmacogenetics/*trends ; Precision Medicine/*trends ; }, abstract = {Personalized medicine is an approach for medical decisions, practices, and interventions that considers individual variations in genes, environment, and lifestyle for each person. Regarding complex metabolic patterns associated with different diseases, characterizing unique metabolic patterns of each patient seems like a practical approach. We can imagine a future in which routinely analyzing the microbiome allows us to predict individualized responses to different foods and drugs. Microbiome analysis of individuals may be added to future routine personalized medicine protocols after comparing the costs and benefits of microbiome-sequencing technology. Moreover, improved understanding of the human microbiome could lead to the development of novel therapeutic strategies for different diseases. Potential therapeutic agents, such as personalized probiotic and prebiotic supplements, dietary interventions, and fecal microbiota transplantation that can be used to reshape the gut microbiome, represent a reasonable strategy in an era of personalized medicine.}, }
@article {pmid28985671, year = {2017}, author = {Tse, BN and Adalja, AA and Houchens, C and Larsen, J and Inglesby, TV and Hatchett, R}, title = {Challenges and Opportunities of Nontraditional Approaches to Treating Bacterial Infections.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {3}, pages = {495-500}, pmid = {28985671}, issn = {1537-6591}, support = {U38 CE002353/CE/NCIPC CDC HHS/United States ; }, mesh = {Antibodies, Monoclonal/therapeutic use ; Bacterial Infections/*therapy ; Drug Resistance, Bacterial ; Fecal Microbiota Transplantation ; Humans ; Immunologic Factors/therapeutic use ; Microbiota ; Phage Therapy ; Therapeutics/methods/trends ; }, abstract = {Due to increasing rates of antimicrobial-resistant infections and the current inadequacy of the antibiotic pipeline, there is increasing interest in nontraditional approaches to antibacterial therapies. We define "traditional" agents as small-molecule agents that directly target bacterial components to exert a bacteriostatic or bactericidal effect, and "nontraditional approaches" as antimicrobial therapeutics that work through other means (ie, not a small molecule and/or utilizes a nontraditional target). Due to their atypical features, such therapies may be less susceptible to the emergence of resistance than traditional antibiotics. They include approaches such as monoclonal antibodies, virulence disruptors, immunomodulators, phage therapies, microbiome-based therapies, antibiotic potentiators, and antisense approaches. This article discusses both the developmental and regulatory advantages and challenges associated with each of these technologies. By identifying existing regulatory and developmental gaps, we hope to provide a sense of where focusing resources may provide the greatest impact on successful product development.}, }
@article {pmid28983003, year = {2017}, author = {Mongodin, EF and Hittle, LL and Nadendla, S and Brinkman, CC and Xiong, Y and Bromberg, JS}, title = {Complete Genome Sequence of a Strain of Bifidobacterium pseudolongum Isolated from Mouse Feces and Associated with Improved Organ Transplant Outcome.}, journal = {Genome announcements}, volume = {5}, number = {40}, pages = {}, pmid = {28983003}, issn = {2169-8287}, abstract = {Here, we report the complete genome sequence of Bifidobacterium pseudolongum strain UMB-MBP-01, isolated from the feces of C57BL/6J mice. This strain was identified in microbiome profiling studies and associated with improved transplant outcome in a murine model of cardiac heterotypic transplantation.}, }
@article {pmid28980505, year = {2017}, author = {Cataldo, MA and Granata, G and Petrosillo, N}, title = {Clostridium difficile infection: new approaches to prevention, non-antimicrobial treatment, and stewardship.}, journal = {Expert review of anti-infective therapy}, volume = {15}, number = {11}, pages = {1027-1040}, doi = {10.1080/14787210.2017.1387535}, pmid = {28980505}, issn = {1744-8336}, mesh = {Aminoglycosides/metabolism/*therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Antimicrobial Stewardship/*organization &amp; administration ; Clostridioides difficile/drug effects/growth &amp; development/pathogenicity ; Clostridium Infections/microbiology/pathology/*therapy ; Cross Infection/prevention &amp; control ; *Fecal Microbiota Transplantation ; Fidaxomicin ; Hand Hygiene/organization &amp; administration ; Humans ; Incidence ; Infection Control/*methods ; Probiotics/therapeutic use ; Spores, Bacterial/drug effects/growth &amp; development/pathogenicity ; }, abstract = {Despite the large amount of scientific publications exploring the epidemiology and the clinical management of Clostridium difficile (CD) infection, some issues remain unsolved or need further studies. The aim of this review is to give an update on the hot topics on CD prevention, including stewardship programs, and on the non-microbiological treatment of CD infection. Areas covered: This article will review the importance of minimizing the CD spore shedding in the healthcare environment for potentially reducing CD transmission. Moreover, antimicrobial stewardship programs aimed to reduce CD incidence will be reviewed. Finally, new strategies for reducing CD infection recurrence will be described. Expert commentary: Besides the basic infection control and prevention practices, including hand hygiene, contact isolation and environmental cleaning, in the prevention of CD infection other issues should be addressed including minimizing the spread of CD in the healthcare setting, and implementing the best strategy for reducing CD infection occurrence, including tailored antimicrobial stewardship programs. Regarding new advancements in treatment and management of CDI episodes, non-antimicrobial approaches seem to be promising in reducing and managing recurrent CD infection.}, }
@article {pmid28980453, year = {2018}, author = {Bircher, L and Schwab, C and Geirnaert, A and Lacroix, C}, title = {Cryopreservation of artificial gut microbiota produced with in vitro fermentation technology.}, journal = {Microbial biotechnology}, volume = {11}, number = {1}, pages = {163-175}, pmid = {28980453}, issn = {1751-7915}, mesh = {Acetates/metabolism ; Butyrates/metabolism ; Cryopreservation/*methods ; Cryoprotective Agents/pharmacology ; Fermentation ; *Gastrointestinal Microbiome ; Glycerol/pharmacology ; Inulin/pharmacology ; Microbiological Techniques/*methods ; Propionates/metabolism ; }, abstract = {Interest in faecal microbiota transplantation (FMT) has increased as therapy for intestinal diseases, but safety issues limit its widespread use. Intestinal fermentation technology (IFT) can produce controlled, diverse and metabolically active 'artificial' colonic microbiota as potential alternative to common FMT. However, suitable processing technology to store this artificial microbiota is lacking. In this study, we evaluated the impact of the two cryoprotectives, glycerol (15% v/v) and inulin (5% w/v) alone and in combination, in preserving short-chain fatty acid formation and recovery of major butyrate-producing bacteria in three artificial microbiota during cryopreservation for 3 months at -80°C. After 24 h anaerobic fermentation of the preserved microbiota, butyrate and propionate production were maintained when glycerol was used as cryoprotectant, while acetate and butyrate were formed more rapidly with glycerol in combination with inulin. Glycerol supported cryopreservation of the Roseburia spp./Eubacterium rectale group, while inulin improved the recovery of Faecalibacterium prausnitzii. Eubacterium hallii growth was affected minimally by cryopreservation. Our data indicate that butyrate producers, which are key organisms for gut health, can be well preserved with glycerol and inulin during frozen storage. This is of high importance if artificially produced colonic microbiota is considered for therapeutic purposes.}, }
@article {pmid28978426, year = {2017}, author = {Kootte, RS and Levin, E and Salojärvi, J and Smits, LP and Hartstra, AV and Udayappan, SD and Hermes, G and Bouter, KE and Koopen, AM and Holst, JJ and Knop, FK and Blaak, EE and Zhao, J and Smidt, H and Harms, AC and Hankemeijer, T and Bergman, JJGHM and Romijn, HA and Schaap, FG and Olde Damink, SWM and Ackermans, MT and Dallinga-Thie, GM and Zoetendal, E and de Vos, WM and Serlie, MJ and Stroes, ESG and Groen, AK and Nieuwdorp, M}, title = {Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition.}, journal = {Cell metabolism}, volume = {26}, number = {4}, pages = {611-619.e6}, doi = {10.1016/j.cmet.2017.09.008}, pmid = {28978426}, issn = {1932-7420}, mesh = {Blood Glucose/analysis/metabolism ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Insulin Resistance ; Male ; Metabolic Syndrome/blood/metabolism/microbiology/*therapy ; Middle Aged ; Transplantation, Autologous/methods ; Transplantation, Homologous/methods ; gamma-Aminobutyric Acid/blood/metabolism ; }, abstract = {The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as γ-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.}, }
@article {pmid28976455, year = {2017}, author = {Brandt, LJ}, title = {Fecal Microbiota Therapy With a Focus on Clostridium difficile Infection.}, journal = {Psychosomatic medicine}, volume = {79}, number = {8}, pages = {868-873}, doi = {10.1097/PSY.0000000000000511}, pmid = {28976455}, issn = {1534-7796}, mesh = {Clostridium Infections/*therapy ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {There has been a paradigm shift in our view of bacteria away from their role as just pathogens. We now have a deepening appreciation of their critical influences in our health maintenance, including energy harvest, metabolism, intestinal development, cell proliferation, nervous system and immune function, as well as their role to protect against intestinal and other infections. A perturbed intestinal microbiome has been associated with an increasing number of gastrointestinal and nongastrointestinal diseases but particularly with Clostridium difficile infection (CDI). Although such association does not imply causation, it has been shown that fecal microbiota transplantation (FMT) can correct the dysbiosis that characterizes chronic and recurring CDI and that FMT can effect a seemingly safe and rapidly effective cure for most patients with CDI so treated. FMT has been used to treat a wide range of other diseases, although conclusions about efficacy in any disease other than CDI must await appropriate well-designed trials. More work needs to be conducted with FMT, especially to evaluate and ensure its long-term safety. Future studies are likely to narrow the spectrum of organisms that needs to be given to patients to cure CDI, and perhaps other diseases, and to elucidate the mechanisms whereby such therapeutic benefit occurs. FMT is but the first step in this journey.}, }
@article {pmid28968189, year = {2018}, author = {Vázquez-Baeza, Y and Callewaert, C and Debelius, J and Hyde, E and Marotz, C and Morton, JT and Swafford, A and Vrbanac, A and Dorrestein, PC and Knight, R}, title = {Impacts of the Human Gut Microbiome on Therapeutics.}, journal = {Annual review of pharmacology and toxicology}, volume = {58}, number = {}, pages = {253-270}, doi = {10.1146/annurev-pharmtox-042017-031849}, pmid = {28968189}, issn = {1545-4304}, mesh = {Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology/therapeutic use ; Antineoplastic Agents/pharmacology/therapeutic use ; Cardiac Glycosides/pharmacology/therapeutic use ; Gastrointestinal Microbiome/*drug effects/*physiology ; Humans ; Microbiota/*drug effects/*physiology ; Signal Transduction/drug effects ; }, abstract = {The human microbiome contains a vast source of genetic and biochemical variation, and its impacts on therapeutic responses are just beginning to be understood. This expanded understanding is especially important because the human microbiome differs far more among different people than does the human genome, and it is also dramatically easier to change. Here, we describe some of the major factors driving differences in the human microbiome among individuals and populations. We then describe some of the many ways in which gut microbes modify the action of specific chemotherapeutic agents, including nonsteroidal anti-inflammatory drugs and cardiac glycosides, and outline the potential of fecal microbiota transplant as a therapeutic. Intriguingly, microbes also alter how hosts respond to therapeutic agents through various pathways acting at distal sites. Finally, we discuss some of the computational and practical issues surrounding use of the microbiome to stratify individuals for drug response, and we envision a future where the microbiome will be modified to increase everyone's potential to benefit from therapy.}, }
@article {pmid28967895, year = {2017}, author = {Liu, C and Frank, DN and Horch, M and Chau, S and Ir, D and Horch, EA and Tretina, K and van Besien, K and Lozupone, CA and Nguyen, VH}, title = {Associations between acute gastrointestinal GvHD and the baseline gut microbiota of allogeneic hematopoietic stem cell transplant recipients and donors.}, journal = {Bone marrow transplantation}, volume = {52}, number = {12}, pages = {1643-1650}, doi = {10.1038/bmt.2017.200}, pmid = {28967895}, issn = {1476-5365}, mesh = {Adult ; Aged ; Female ; Gastrointestinal Diseases/*etiology ; *Gastrointestinal Microbiome ; Graft vs Host Disease/*pathology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Male ; Middle Aged ; RNA, Ribosomal, 16S/analysis ; Tissue Donors ; Transplant Recipients ; }, abstract = {Growing evidence suggests that host-microbiota interactions influence GvHD risk following allogeneic hematopoietic stem cell transplant. However, little is known about the influence of the transplant recipient's pre-conditioning microbiota nor the influence of the transplant donor's microbiota. Our study examines associations between acute gastrointestinal GvHD (agGvHD) and 16S rRNA fecal bacterial profiles in a prospective cohort of N=57 recipients before preparative conditioning, as well as N=22 of their paired HLA-matched sibling donors. On average, recipients had lower fecal bacterial diversity (P=0.0002) and different phylogenetic membership (UniFrac P=0.001) than the healthy transplant donors. Recipients with lower phylogenetic diversity had higher overall mortality rates (hazard ratio=0.37, P=0.008), but no statistically significant difference in agGvHD risk. In contrast, high bacterial donor diversity was associated with decreased agGvHD risk (odds ratio=0.12, P=0.038). Further investigation is warranted as to whether selection of hematopoietic stem cell transplant donors with high gut microbiota diversity and/or other specific compositional attributes may reduce agGvHD incidence, and by what mechanisms.}, }
@article {pmid28957972, year = {2017}, author = {}, title = {Process and Outcome of Fecal Microbiota Transplants in Patients With Recurrent Clostridium difficile Infection: A Prospective Study.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {40}, number = {5}, pages = {E1-E2}, doi = {10.1097/SGA.0000000000000325}, pmid = {28957972}, issn = {1538-9766}, }
@article {pmid28957971, year = {2017}, author = {Walton, J and Burns, D and Gaehle, KE}, title = {Process and Outcome of Fecal Microbiota Transplants in Patients With Recurrent Clostridium difficile Infection: A Prospective Study.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {40}, number = {5}, pages = {411-419}, doi = {10.1097/SGA.0000000000000233}, pmid = {28957971}, issn = {1538-9766}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/therapy ; Cohort Studies ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Male ; Prospective Studies ; *Quality of Life ; Recurrence ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {The incidence of Clostridium difficile infection is on the rise worldwide, causing high mortality rates and costing patients, hospitals, and insurance companies millions of dollars annually. Fecal microbiota transplants successfully treat recurrent C. difficile infections unresponsive to standard pharmacologic treatment such as flagyl, vancomycin, or rifaximin. Evidence in the literature provided the foundation for the development and refinement of this fecal microbiota transplant protocol. During the initial phase of the project, the protocol included patient selection criteria, donor screening/selection, infection control, fecal processing and delivery, and patient pre and postprocedure education. This article highlights the second phase of prospective testing of a nurse-driven protocol to implement fecal microbiota transplantation in patients with recurrent C. difficile infection. All stages of the protocol are explained as well as rationale for component parts to achieve successful patient outcomes when the protocol is carefully followed.}, }
@article {pmid28951890, year = {2017}, author = {Miller, AW and Dale, C and Dearing, MD}, title = {The Induction of Oxalate Metabolism In Vivo Is More Effective with Functional Microbial Communities than with Functional Microbial Species.}, journal = {mSystems}, volume = {2}, number = {5}, pages = {}, pmid = {28951890}, issn = {2379-5077}, support = {F32 DK102277/DK/NIDDK NIH HHS/United States ; }, abstract = {For mammals, oxalate enters the body through the diet or is endogenously produced by the liver; it is removed by microbial oxalate metabolism in the gut and/or excretion in feces or urine. Deficiencies in any one of the these pathways can lead to complications, such as calcium oxalate urinary stones. While considerable research has been conducted on individual oxalate-degrading bacterial isolates, interactions between oxalate and the gut microbiota as a whole are unknown. We examined the reduction in oxalate excretion in a rat model following oral administration of fecal microbes from a mammalian herbivore adapted to a high oxalate diet or to fecal transplants consisting of two different formulations of mixed oxalate-degrading isolates. While all transplants elicited a significant reduction in oxalate excretion initially, the greatest effect was seen with fecal microbial transplants, which persisted even in the absence of dietary oxalate. The reduction in oxalate excretion in animals given fecal transplants corresponded with the establishment of diverse bacteria, including known oxalate-degrading bacteria and a cohesive network of bacteria centered on oxalate-degrading specialists from the Oxalobacteraceae family. Results suggested that the administration of a complete community of bacteria facilitates a cohesive balance in terms of microbial interactions. Our work offers important insights into the development of targeted bacteriotherapies intended to reduce urinary oxalate excretion in patients at risk for recurrent calcium oxalate stones as well as bacteriotherapies targeting other toxins for elimination. IMPORTANCE Oxalate is a central component in 80% of kidney stones. While mammals do not possess the enzymes to degrade oxalate, many gastrointestinal bacteria are efficient oxalate degraders. We examined the role of cohesive microbial networks for oxalate metabolism, using Sprague-Dawley rats as a model host. While the transplantation of oxalate-degrading bacteria alone to the Sprague-Dawley hosts did increase oxalate metabolism, fecal transplants from a wild mammalian herbivore, Neotoma albigula, had a significantly greater effect. Furthermore, the boost for oxalate metabolism persisted only in animals that received fecal transplants. Animals receiving fecal transplants had a more diverse and cohesive network of bacteria associated with the Oxalobacteraceae, a family known to consist of specialist oxalate-degrading bacteria, than did animals that received oxalate-degrading bacteria alone. Our results indicate that fecal transplants are more effective at transferring specific functions than are microbial specialists alone, which has broad implications for the development of bacteriotherapies.}, }
@article {pmid28942372, year = {2018}, author = {Leonel, ECR and Vilela, JMV and Paiva, REG and Jivago, JLPR and Amaral, RS and Lucci, CM}, title = {Restoration of fresh cat ovarian tissue function by autografting to subcutaneous tissue: A pilot study.}, journal = {Theriogenology}, volume = {105}, number = {}, pages = {97-106}, doi = {10.1016/j.theriogenology.2017.09.016}, pmid = {28942372}, issn = {1879-3231}, mesh = {Animals ; Cats/*physiology ; Female ; Ovary/*transplantation ; Pilot Projects ; Subcutaneous Tissue/*physiology ; Tissue Transplantation/*veterinary ; }, abstract = {Ovarian tissue transplantation could be a valuable technique for the preservation of endangered animals. The domestic cat affords an adequate experimental model for studies aimed at wild felids due to its phylogenetic similarity. Thus, this pilot study evaluated the efficacy of cat ovarian tissue autotransplantation to a peripheral site. Three adult queens were submitted to ovariohysterectomy. The ovaries were fragmented into eight pieces; two were fixed as a control and six were transplanted to subcutaneous tissue of the dorsal neck. Grafts were monitored weekly by ultrasound and fecal samples collected daily in order to monitor estradiol levels. Grafts were recovered on Days: 7, 14, 28, 49 and 63 post-transplantation for histological analyses. One graft was maintained in one animal for 8 months. A total of 2466 ovarian follicles were analyzed: 1406 primordial and 1060 growing follicles. All animals presented antral follicles in one or more of the grafts. The percentage of morphologically normal primordial follicles was always higher than 80%, except for Day 7 transplants. Although the proportion of growing follicles increased after transplantation, there was a general decrease in the percentage of morphologically normal growing follicles from Day 7 onwards. All animals demonstrated at least three estradiol peaks during the 63-day period, and one animal exhibited estrous behaviour on three occasions. Hormonal peaks directly correlated with the visualization of antral follicles (by ultrasound and/or histology) and the observation of estrous behaviour. Long-term results on one female showed the concentration of 37.8 pg/mL of serum estradiol on Day 233 post-grafting and the female exhibited estrous behaviour on several occasions. This graft showed one antral follicle, one luteinized follicle and two preantral follicles. In conclusion, cat ovary autotransplantation to the subcutaneous tissue restored ovarian function, with hormone production and antral follicle development, over both short and long term periods. This could be a valuable technique in the evaluation of ovarian cryopreservation methods in felids. Once the technique is shown successful, it may be applied in allografts or xenografts between different feline species.}, }
@article {pmid28942047, year = {2017}, author = {Kotková, M and Sak, B and Hlásková, L and Kváč, M}, title = {The course of infection caused by Encephalitozoon cuniculi genotype III in immunocompetent and immunodeficient mice.}, journal = {Experimental parasitology}, volume = {182}, number = {}, pages = {16-21}, doi = {10.1016/j.exppara.2017.09.022}, pmid = {28942047}, issn = {1090-2449}, mesh = {Albendazole/pharmacology/*therapeutic use ; Animals ; Antifungal Agents/pharmacology/therapeutic use ; Encephalitozoon cuniculi/drug effects/genetics/immunology/*physiology ; Encephalitozoonosis/drug therapy/*immunology/parasitology ; Feces/parasitology ; Genotype ; *Immunocompetence ; *Immunocompromised Host ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Spores, Fungal ; }, abstract = {Encephalitozoon cuniculi is probably the most common microsporidia which infects a wide range of vertebrates, including human. So far, four genotypes of this parasite have been identified based on the rRNA internal transcribed spacer variations. The course of infection caused by E. cuniculi III had very massive onset in immunocompetent host characterized by the presence of this parasite in all organs and tissues within one week after peroral infection. Encephalitozoonosis caused by E. cuniculi III had very progressive spreading into all organs within first week post inoculation in immunocompromised SCID mice and led to the death of the host. The experimental treatment with albendazole of immunocompetent BALB/c mice infected with E. cuniculi III have shown very weak effect. Our findings clearly showed that the different course of infection and response to treatment depends not only on the immunological status of the host, but also on the genotype of microsporidia. It could be very important especially for individuals under chemotherapy and transplant recipients of organs originating from infected donors.}, }
@article {pmid28939450, year = {2018}, author = {Cobo, J and Merino, E and Martínez, C and Cózar-Llistó, A and Shaw, E and Marrodán, T and Calbo, E and Bereciartúa, E and Sánchez-Muñoz, LA and Salavert, M and Pérez-Rodríguez, MT and García-Rosado, D and Bravo-Ferrer, JM and Gálvez-Acebal, J and Henríquez-Camacho, C and Cuquet, J and Pino-Calm, B and Torres, L and Sánchez-Porto, A and Fernández-Félix, BM and , }, title = {Prediction of recurrent clostridium difficile infection at the bedside: the GEIH-CDI score.}, journal = {International journal of antimicrobial agents}, volume = {51}, number = {3}, pages = {393-398}, doi = {10.1016/j.ijantimicag.2017.09.010}, pmid = {28939450}, issn = {1872-7913}, mesh = {Aged ; Aged, 80 and over ; Clostridium Infections/*diagnosis ; *Decision Support Techniques ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; *Recurrence ; }, abstract = {Recurrence of Clostridium difficile infection (CDI) has major consequences for both patients and the health system. The ability to predict which patients are at increased risk of recurrent CDI makes it possible to select candidates for treatment with new drugs and therapies (including fecal microbiota transplantation) that have proven to reduce the incidence of recurrence of CDI. Our objective was to develop a clinical prediction tool, the GEIH-CDI score, to determine the risk of recurrence of CDI. Predictors of recurrence of CDI were investigated using logistic regression in a prospective cohort of 274 patients diagnosed with CDI. The model was calibrated using the Hosmer-Lemeshow test. The tool comprises four factors: age (70-79 years and ≥80 years), history of CDI during the previous year, direct detection of toxin in stool, and persistence of diarrhea on the fifth day of treatment. The functioning of the GEIH-CDI score was validated in a prospective cohort of 183 patients. The area under the ROC curve was 0.72 (0.65-0.79). Application of the tool makes it possible to select patients at high risk (>50%) of recurrence and patients at low risk (<10%) of recurrence. GEIH-CDI score may be useful for clinicians treating patients with CDI.}, }
@article {pmid28936973, year = {2017}, author = {Karakan, T}, title = {Fecal microbiota transplantation for treating recurrent hepatic encephalopathy: Ready for clinical application?.}, journal = {The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology}, volume = {28}, number = {5}, pages = {425-426}, doi = {10.5152/tjg.2017.18817}, pmid = {28936973}, issn = {2148-5607}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous ; *Fecal Microbiota Transplantation ; Feces ; *Hepatic Encephalopathy ; Humans ; Microbiota ; }, }
@article {pmid28936948, year = {2017}, author = {Collins, J and Auchtung, JM}, title = {Control of Clostridium difficile Infection by Defined Microbial Communities.}, journal = {Microbiology spectrum}, volume = {5}, number = {5}, pages = {}, pmid = {28936948}, issn = {2165-0497}, support = {R21 AI121522/AI/NIAID NIH HHS/United States ; R33 AI121522/AI/NIAID NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Clostridioides difficile/genetics/isolation &amp; purification/*physiology ; Clostridium Infections/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; }, abstract = {Each year in the United States, billions of dollars are spent combating almost half a million Clostridium difficile infections (CDIs) and trying to reduce the ∼29,000 patient deaths in which C. difficile has an attributed role. In Europe, disease prevalence varies by country and level of surveillance, though yearly costs are estimated at €3 billion. One factor contributing to the significant health care burden of C. difficile is the relatively high frequency of recurrent CDIs. Recurrent CDI, i.e., a second episode of symptomatic CDI occurring within 8 weeks of successful initial CDI treatment, occurs in ∼25% of patients, with 35 to 65% of these patients experiencing multiple episodes of recurrent disease. Using microbial communities to treat recurrent CDI, either as whole fecal transplants or as defined consortia of bacterial isolates, has shown great success (in the case of fecal transplants) or potential promise (in the case of defined consortia of isolates). This review will briefly summarize the epidemiology and physiology of C. difficile infection, describe our current understanding of how fecal microbiota transplants treat recurrent CDI, and outline potential ways that knowledge can be used to rationally design and test alternative microbe-based therapeutics.}, }
@article {pmid28932754, year = {2017}, author = {Rebello, D and Wang, E and Yen, E and Lio, PA and Kelly, CR}, title = {Hair Growth in Two Alopecia Patients after Fecal Microbiota Transplant.}, journal = {ACG case reports journal}, volume = {4}, number = {}, pages = {e107}, pmid = {28932754}, issn = {2326-3253}, abstract = {Clostridium difficile infections can be life-threatening but are increasingly being treated successfully with fecal microbiota transplantation (FMT). We report two patients with alopecia universalis who developed subsequent hair regrowth after FMT for treatment of recurrent C. difficile infections. Gut microbiota may have immunomodulatory effects in autoimmune conditions such as alopecia areata, and further study may elucidate disease mechanisms and lead to alternative treatment options for these patients for whom treatment options are currently limited.}, }
@article {pmid28931467, year = {2017}, author = {Chao, AW and Bhatti, M and DuPont, HL and Nataro, JP and Carlin, LG and Okhuysen, PC}, title = {Clinical features and molecular epidemiology of diarrheagenic Escherichia coli pathotypes identified by fecal gastrointestinal multiplex nucleic acid amplification in patients with cancer and diarrhea.}, journal = {Diagnostic microbiology and infectious disease}, volume = {89}, number = {3}, pages = {235-240}, doi = {10.1016/j.diagmicrobio.2017.08.004}, pmid = {28931467}, issn = {1879-0070}, mesh = {Adolescent ; Adult ; Aged ; Anti-Bacterial Agents/pharmacology ; Diarrhea/*microbiology ; Drug Resistance, Bacterial ; Escherichia coli/drug effects/*genetics/isolation &amp; purification ; Escherichia coli Infections/etiology/*microbiology ; Feces/*microbiology ; Female ; Humans ; Male ; Middle Aged ; *Molecular Epidemiology ; Neoplasms/*complications ; Nucleic Acid Amplification Techniques ; Real-Time Polymerase Chain Reaction ; Young Adult ; }, abstract = {Diarrheagenic Escherichia coli (DEC) pathotypes with differing epidemiology and clinical features, are known causes of disease with worldwide occurrence. At a major cancer center in the U.S., we studied patients with cancer and diarrhea for whom a GI Biofire FilmArray multiplex GI panel (BFM) was performed. An enteropathogen was identified in 382 of 2017 (19%) samples distributed across 311 patients. Of these, 60/311(19%) were positive for DEC. Patients receiving hematopoietic stem cell transplants (HSCT) 29/60 (48%) or with a hematologic malignancy 17/60 (28%) accounted for the majority of DEC cases. Enteropathogenic E. coli (EPEC, n=35 [58%]), enteroaggregative E. coli (EAEC, n=10 [17%]) and Shiga toxin producing E. coli (STEC, n=3 [5%]) were the most common DEC identified and peaked in the summer months. Stool cultures confirmed infections in 6/10 (60%) EAEC (five typical AggR[+]), and EPEC was recovered in 8/35 (22%) samples (all atypical eaeA[+], bfp[-]). DEC was identified in 22 cases (37%) that developed diarrhea >48hours after admission suggesting health care acquisition. Chronic infections were found in 2 EPEC and 1 EAEC cases that were tested at 1month or beyond with shedding that ranged from 58 to >125days. Two patients that underwent hematopoietic stem cell transplantation carried EAEC strains resistant to multiple antibiotics including fluoroquinolones and expressed extended spectrum beta lactamases. While in some instances BFM results were not verified in culture and could represent false positives, DEC pathotypes, especially EPEC and EAEC, caused chronic infections with antimicrobial-resistant strains in a subset of immunosuppressed cancer patients.}, }
@article {pmid28928747, year = {2017}, author = {van den Hoogen, WJ and Laman, JD and 't Hart, BA}, title = {Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota.}, journal = {Frontiers in immunology}, volume = {8}, number = {}, pages = {1081}, pmid = {28928747}, issn = {1664-3224}, abstract = {Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research.}, }
@article {pmid28927251, year = {2017}, author = {Bibbò, S and Ianiro, G and Gasbarrini, A and Cammarota, G}, title = {Fecal microbiota transplantation: past, present and future perspectives.}, journal = {Minerva gastroenterologica e dietologica}, volume = {63}, number = {4}, pages = {420-430}, doi = {10.23736/S1121-421X.17.02374-1}, pmid = {28927251}, issn = {1827-1642}, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/methods/*trends ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*therapy ; Irritable Bowel Syndrome/therapy ; Metabolic Diseases/*therapy ; Treatment Outcome ; }, abstract = {Gut microbiota is known to play a main role in regulating both health and disease in humans. Strategies for the therapeutic modulation of gut microbiota are therefore expected to give a relevant contribution in the management of disorders associated with its impairment. Among these options, one of the most renowned is fecal microbiota transplantation (FMT). A growing body of evidence showed clearly that FMT is an effective treatment against recurrent Clostridium difficile infection. Moreover, it was shown to be a promising therapy for the management of several noncommunicable disorders, including inflammatory bowel diseases and metabolic disorders. Standardization of procedural protocols for different disorders will surely increase the therapeutic power of FMT. The aim of this narrative review was to make an overview of methodology, indications, and future perspectives of FMT for the management of disorders associated with gut microbiota impairment.}, }
@article {pmid28923757, year = {2018}, author = {Kelly, BJ and Tebas, P}, title = {Clinical Practice and Infrastructure Review of Fecal Microbiota Transplantation for Clostridium difficile Infection.}, journal = {Chest}, volume = {153}, number = {1}, pages = {266-277}, pmid = {28923757}, issn = {1931-3543}, support = {K23 AI121485/AI/NIAID NIH HHS/United States ; L30 AI120149/AI/NIAID NIH HHS/United States ; U54 CK000485/CK/NCEZID CDC HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Clostridium Infections/diagnosis/*therapy ; Diffusion of Innovation ; Donor Selection/methods ; Fecal Microbiota Transplantation/*methods ; Humans ; Middle Aged ; Young Adult ; }, abstract = {A substantial proportion of Clostridium difficile infection (CDI) cases recur after completion of antibiotic therapy, and antibiotic cure rates diminish with each recurrence of CDI. Fecal microbiota transplantation (FMT) is an effective therapy for recurrent FMT, which otherwise requires prolonged or indefinite antibiotic treatment. FMT is performed by introducing the fecal microbial community obtained from a healthy donor or pool of donors into the stomach, small intestine, or colon of a patient with CDI. Multiple clinical trials support the usefulness of FMT in treating recurrent CDI, and CDI treatment guidelines now include consideration of FMT at the third CDI recurrence. However, there remain challenges to incorporating FMT into clinical practice. First, methods of fecal bacterial community processing vary, as do methods of FMT administration. Second, the optimal dosing strategy and expected benefit of FMT for refractory CDI, particularly for severe and severe complicated cases, are uncertain. Third, the US Food and Drug Administration (FDA) considers FMT an investigational treatment. Fourth, insurance reimbursement for FMT usually falls short of FMT administration costs. In the setting of rising C difficile incidence and growing evidence for FMT efficacy, the demand for FMT has increased. However, uncertainty surrounding optimal FMT preparation and administration methods, FDA oversight, and insurance reimbursement presently limits the clinical practice of FMT.}, }
@article {pmid28916525, year = {2017}, author = {Redfern, A and Suchodolski, J and Jergens, A}, title = {Role of the gastrointestinal microbiota in small animal health and disease.}, journal = {The Veterinary record}, volume = {181}, number = {14}, pages = {370}, doi = {10.1136/vr.103826}, pmid = {28916525}, issn = {2042-7670}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Dog Diseases/*microbiology/*therapy ; Dogs ; Dysbiosis/veterinary ; Fecal Microbiota Transplantation/veterinary ; Feces/microbiology ; Gastrointestinal Diseases/microbiology/therapy/*veterinary ; *Gastrointestinal Microbiome ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {There is a large and emerging interest in the role of the gastrointestinal microbiota in health and disease. This paper serves to review the current knowledge and recommendations of the gastrointestinal microbiota in health and gastrointestinal disease. Further, this review evaluates the current literature and suggests guidelines for faecal microbial transplantation, a novel therapy for dysbiosis in veterinary medicine.}, }
@article {pmid28914862, year = {2017}, author = {Aitbaev, KA and Murkamilov, IT and Fomin, VV}, title = {[Liver diseases: The pathogenetic role of the gut microbiome and the potential of treatment for its modulation].}, journal = {Terapevticheskii arkhiv}, volume = {89}, number = {8}, pages = {120-128}, doi = {10.17116/terarkh2017898120-128}, pmid = {28914862}, issn = {0040-3660}, mesh = {Disease Progression ; *Dysbiosis/diagnosis/therapy ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome/drug effects/physiology ; Humans ; *Liver Diseases/diagnosis/microbiology/physiopathology/prevention &amp; control ; Probiotics/*therapeutic use ; Treatment Outcome ; }, abstract = {The paper gives an update on the role of the gut microbiome (GM) in the development of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, alcoholic liver disease, liver cirrhosis (LC), and its complications, such as hepatic encephalopathy (HE) and hepatocellular carcinoma (HCC), and discusses the possibilities of its correction with prebiotics, probiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The pathophysiology of the liver diseases in question demonstrates some common features that are characterized by pathogenic changes in the composition of the gastrointestinal tract microflora, by intestinal barrier impairments, by development of endotoxemia, by increased liver expression of proinflammatory factors, and by development of liver inflammation. In progressive liver disease, the above changes are more pronounced, which contributes to the development of LC, HE, and HCC. GM modulation using prebiotics, probiotics, synbiotics, antibiotics, and FMT diminishes dysbacteriosis, strengthens the intestinal mucosal barrier, reduces endotoxemia and liver damage, and positively affects the clinical manifestations of HE. Further investigations are needed, especially in humans, firstly, to assess a relationship of GM to the development of liver diseases in more detail and, secondly, to obtain evidence indicating the therapeutic efficacy of GM-modulating agents in large-scale, well-designed, randomized, controlled, multicenter studies.}, }
@article {pmid28906291, year = {2017}, author = {Narula, N and Kassam, Z and Yuan, Y and Colombel, JF and Ponsioen, C and Reinisch, W and Moayyedi, P}, title = {Systematic Review and Meta-analysis: Fecal Microbiota Transplantation for Treatment of Active Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {23}, number = {10}, pages = {1702-1709}, doi = {10.1097/MIB.0000000000001228}, pmid = {28906291}, issn = {1536-4844}, mesh = {Colitis, Ulcerative/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: Changes in the colonic microbiota may play a role in the pathogenesis of ulcerative colitis (UC) and restoration of healthy gut microbiota may ameliorate disease. A systematic review and meta-analysis was conducted to assess fecal microbiota transplantation (FMT) as a treatment for active UC.<br><br>METHODS: A literature search was conducted to identify high-quality studies of FMT as a treatment for patients with UC. The primary outcome was combined clinical remission and endoscopic remission or response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Odds ratios with 95% confidence intervals (CIs) are reported.<br><br>RESULTS: Overall, 4 studies with 277 participants were eligible for inclusion. Among 4 randomized controlled trials, FMT was associated with higher combined clinical and endoscopic remission compared with placebo (risk ratio UC not in remission was 0.80; 95% CI: 0.71-0.89) with a number needed to treat of 5 (95% CI: 4-10). There was no statistically significant increase in serious adverse events with FMT compared with controls (risk ratio adverse event was 1.4; 95% CI: 0.55-3.58).<br><br>CONCLUSIONS: Among randomized controlled trials, short-term use of FMT shows promise as a treatment to induce remission in active UC based on the efficacy and safety observed. However, there remain many unanswered questions that require further research before FMT can be considered for use in clinical practice.}, }
@article {pmid28902124, year = {2017}, author = {Tronstad, RR and Kummen, M and Holm, K and von Volkmann, HL and Anmarkrud, JA and Høivik, ML and Moum, B and Gilja, OH and Hausken, T and Baines, J and Karlsen, TH and Fiskerstrand, T and Hov, JR}, title = {Guanylate Cyclase C Activation Shapes the Intestinal Microbiota in Patients with Familial Diarrhea and Increased Susceptibility for Crohn's Disease.}, journal = {Inflammatory bowel diseases}, volume = {23}, number = {10}, pages = {1752-1761}, doi = {10.1097/MIB.0000000000001264}, pmid = {28902124}, issn = {1536-4844}, mesh = {Adult ; Case-Control Studies ; Crohn Disease/complications/*microbiology ; DNA, Bacterial/genetics ; Diarrhea/*genetics/microbiology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Genetic Linkage ; Genetic Predisposition to Disease ; Humans ; Intestinal Mucosa/metabolism ; Male ; Middle Aged ; Mutation, Missense ; Norway ; RNA, Ribosomal, 16S/genetics ; Receptors, Enterotoxin/*genetics ; }, abstract = {BACKGROUND: With 25% prevalence of Crohn's disease, Familial GUCY2C diarrhea syndrome (FGDS) is a monogenic disorder potentially suited to study initiating factors in inflammatory bowel disease (IBD). We aimed to characterize the impact of an activating GUCY2C mutation on the gut microbiota in patients with FGDS controlling for Crohn's disease status and to determine whether changes share features with those observed in unrelated patients with IBD.<br><br>METHODS: Bacterial DNA from fecal samples collected from patients with FGDS (N = 20), healthy relatives (N = 11), unrelated healthy individuals (N = 263), and IBD controls (N = 46) was subjected to sequencing of the V3-V4 region of the 16S rRNA gene to determine gut microbiota composition. Food frequency questionnaires were obtained from patients with FGDS and their relatives.<br><br>RESULTS: Compared with healthy controls, FGDS displayed prominent changes in many microbial lineages including increase in Enterobacteriaceae, loss of Bifidobacterium and Faecalibacterium prausnitzii but an unchanged intraindividual (alpha) diversity. The depletion of F. prausnitzii is in line with what is typically observed in Crohn's disease. There was no significant difference in the dietary profile between the patients and related controls. The gut microbiota in related and unrelated healthy controls was also similar, suggesting that diet and familial factors do not explain the gut microbiota alterations in FGDS.<br><br>CONCLUSIONS: The findings support that the activating mutation in GUCY2C creates an intestinal environment with a major influence on the microbiota, which could contribute to the increased susceptibility to IBD in patients with FGDS.}, }
@article {pmid28900966, year = {2017}, author = {Waggershauser, CH}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {159}, number = {15}, pages = {39}, doi = {10.1007/s15006-017-0006-7}, pmid = {28900966}, issn = {1438-3276}, mesh = {*Colitis ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid28893994, year = {2017}, author = {Berer, K and Gerdes, LA and Cekanaviciute, E and Jia, X and Xiao, L and Xia, Z and Liu, C and Klotz, L and Stauffer, U and Baranzini, SE and Kümpfel, T and Hohlfeld, R and Krishnamoorthy, G and Wekerle, H}, title = {Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {40}, pages = {10719-10724}, pmid = {28893994}, issn = {1091-6490}, support = {K12 GM081266/GM/NIGMS NIH HHS/United States ; R25 NS070680/NS/NINDS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Brain/*immunology/microbiology/pathology ; Cohort Studies ; *Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/*immunology/microbiology/pathology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Metagenomics ; Mice ; Middle Aged ; Multiple Sclerosis/*immunology/microbiology/pathology ; T-Lymphocytes, Regulatory/*immunology ; Young Adult ; }, abstract = {There is emerging evidence that the commensal microbiota has a role in the pathogenesis of multiple sclerosis (MS), a putative autoimmune disease of the CNS. Here, we compared the gut microbial composition of 34 monozygotic twin pairs discordant for MS. While there were no major differences in the overall microbial profiles, we found a significant increase in some taxa such as Akkermansia in untreated MS twins. Furthermore, most notably, when transplanted to a transgenic mouse model of spontaneous brain autoimmunity, MS twin-derived microbiota induced a significantly higher incidence of autoimmunity than the healthy twin-derived microbiota. The microbial profiles of the colonized mice showed a high intraindividual and remarkable temporal stability with several differences, including Sutterella, an organism shown to induce a protective immunoregulatory profile in vitro. Immune cells from mouse recipients of MS-twin samples produced less IL-10 than immune cells from mice colonized with healthy-twin samples. IL-10 may have a regulatory role in spontaneous CNS autoimmunity, as neutralization of the cytokine in mice colonized with healthy-twin fecal samples increased disease incidence. These findings provide evidence that MS-derived microbiota contain factors that precipitate an MS-like autoimmune disease in a transgenic mouse model. They hence encourage the detailed search for protective and pathogenic microbial components in human MS.}, }
@article {pmid28892150, year = {2017}, author = {Sheng, L and Jena, PK and Hu, Y and Liu, HX and Nagar, N and Kalanetra, KM and French, SW and French, SW and Mills, DA and Wan, YY}, title = {Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation.}, journal = {The Journal of pathology}, volume = {243}, number = {4}, pages = {431-441}, pmid = {28892150}, issn = {1096-9896}, support = {R01 CA222490/CA/NCI NIH HHS/United States ; U01 CA179582/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/metabolism ; Bile Acids and Salts/*metabolism ; Butyrates/metabolism/*pharmacology ; Colon/microbiology ; Diet, Western ; Disease Models, Animal ; Dysbiosis ; Fatty Acids/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Genetic Predisposition to Disease ; Hepatitis/*drug therapy/metabolism/microbiology/pathology ; Humans ; Liver/*drug effects/metabolism/pathology ; Liver Neoplasms/*drug therapy/metabolism/microbiology/pathology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasm Transplantation ; Phenotype ; Receptors, Cytoplasmic and Nuclear/deficiency/genetics/*metabolism ; Signal Transduction ; }, abstract = {Dysregulated bile acid (BA) synthesis or reduced farnesoid X receptor (FXR) levels are found in patients having metabolic diseases, autoimmune hepatitis, and liver cirrhosis or cancer. The objective of this study was to establish the relationship between butyrate and dysregulated BA synthesis-induced hepatitis as well as the effect of butyrate in reversing the liver pathology. Wild-type (WT) and FXR knockout (KO) male mice were placed on a control (CD) or western diet (WD) for 15 months. In the presence or absence of butyrate supplementation, feces obtained from 15-month-old WD-fed FXR KO mice, which had severe hepatitis and liver tumors, were transplanted to 7-month-old WD-fed FXR KO for 3 months. Hepatic phenotypes, microbiota profile, and BA composition were analyzed. Butyrate-generating bacteria and colonic butyrate concentration were reduced due to FXR inactivation and further reduced by WD intake. In addition, WD-fed FXR KO male mice had the highest concentration of hepatic β-muricholic acid (β-MCA) and bacteria-generated deoxycholic acid (DCA) accompanied by serious hepatitis. Moreover, dysregulated BA and reduced SCFA signaling co-existed in both human liver cancers and WD-fed FXR KO mice. Microbiota transplantation using butyrate-deficient feces derived from 15-month-old WD-fed FXR KO mice increased hepatic lymphocyte numbers as well as hepatic β-MCA and DCA concentrations. Furthermore, butyrate supplementation reduced hepatic β-MCA as well as DCA and eliminated hepatic lymphocyte infiltration. In conclusion, reduced butyrate contributes to the development of hepatitis in the FXR KO mouse model. In addition, butyrate reverses dysregulated BA synthesis and its associated hepatitis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.}, }
@article {pmid28888700, year = {2018}, author = {Wang, D and Chen, J and Zhu, L and Sang, M and Yu, F and Zhou, Q}, title = {Surgical Repair of Rectovaginal Fistula Using the Modified Martius Procedure: A Step-by-Step Guide.}, journal = {Journal of minimally invasive gynecology}, volume = {25}, number = {4}, pages = {573-575}, doi = {10.1016/j.jmig.2017.08.657}, pmid = {28888700}, issn = {1553-4669}, mesh = {Adult ; Delivery, Obstetric/adverse effects ; Female ; Humans ; Laparoscopy/adverse effects ; Muscle, Skeletal/transplantation ; Pregnancy ; Puerperal Disorders/*surgery ; Quality of Life ; Rectovaginal Fistula/etiology/*surgery ; Rectum/surgery ; Surgical Flaps ; Suture Techniques ; Sutures ; }, abstract = {STUDY OBJECTIVE: To demonstrate the surgical repair of a rectovaginal fistula (RVF) using the modified Martius procedure.<br><br>DESIGN: A step-by-step presentation of the procedure using video (Canadian Task Force classification III).<br><br>SETTING: RVF is abnormal epithelialized connections between the vagina and rectum. Causes of RVF include obstetric trauma, Crohn disease, pelvic irradiation, and postsurgical complications. Many surgical interventions have been developed, from the laparoscopic technique to muscle transposition and even rectal resection. However, the treatment of RVF is a great challenge to gynecologic surgeons because the incidence of RVF is low and there is no high evidence for the best surgical approach to this disease. When RVF is persistent or recurrent, the surrounding tissue is always scarred or damaged, so the interposition of a healthy and well-perfused tissue is an appropriate approach to fistula management. The modified Martius procedure using adipose tissue from the labia major places well-vascularized pedicle in the place of the RVF. Limited studies involving the procedure present favorable successful rates.<br><br>PATIENT: Consent was obtained from the patient. The study was approved by the local ethics committee.<br><br>INTERVENTION: The surgical repair of rectovaginal fistula by the modified Martius procedure is described as follows: The patient is placed in the high lithotomy position. A temporary transurethral urinary catheter is placed preoperatively to keep the operative site clean. The rectovaginal fistula is identified by a fistula probe. A 4-cm incision is made vertically over the left labium majus from the level of the mons pubis to the bottom of the labium to harvest pedicle. It is imperative to ensure adequate length on the flap before transection. Blood supply to the fat-muscle flap is provided superiorly by the external pudendal artery, posteriorly by the internal posterior and laterally by the obturator artery. The fat-muscle flap is dissected in a lateral-to-medial direction and divided in the upper section by two clamps, preserving its posterior aspect intact to maintain its blood supply. After that the fistula is circumcised with a scalpel through the vaginal wall with a margin of healthy tissue. During the process, the rectovaginal septum is opened and wide mobilized so that a multilayer closure can be performed without any tension. Then a subcutaneous tunnel is made from the labium majus to the fistula with a forcep. It is also important to make the tunnel wide enough to easily accommodate the flap. The fat-muscle flap is pulled through the tunnel gently, ensuring proper orientation without kinking the blood supply. The rectal mucosa is sutured in one layer with 3-0 Vicryl in interrupted fashion. The flap is then sutured down to the rectal wall with four single sutures in interrupted fashion. So the rectal and vaginal walls are separated with a healthy, well-vascularized pedicle. In addition, the flap fills in the dead space and enhances granulation tissue. The vaginal mucosa is then closed over the pedicle with 1-0 Vicryl in interrupted suture without tension. The labial incision is closed in layers with absorbable suture. Neither incision is drained.<br><br>MEASUREMENTS AND MAIN RESULTS: In this video, we describe the modified Martius procedure for the management of RVF. We present a 26-year-old woman who suffered from RVF caused by obstetric trauma. She complained of passing flatus and feces through the vagina 1 week after vaginal delivery. Clinical examination performed in the local hospital confirmed RVF 1&#x2009;cm in diameter located in the lower third of the vagina. The fistula was present for about 6 months, which brought psychosocial dysfunction to the patient. She was transferred to our clinic. After examination, the anal sphincter was intact. After mechanical bowel preparation with polyethylene glycol solution, the patient was presented for surgery. The operating time was about 40 minutes. No recurrence or complications were observed at the 4-month follow-up. A protective ileostomy or colostomy was avoided. The patient reestablished intestinal continuity. The functional and cosmetic results were excellent with high patient satisfaction and greatly improved quality of life.<br><br>CONCLUSION: The Martius flap is easy to harvest with minimal external disfigurement and a minimal recovery time. The modified Martius procedure is a feasible adjuvant technique for RVF with excellent postoperative outcomes.}, }
@article {pmid28882888, year = {2017}, author = {Versalovic, J and Dore, J and Guarner, F and Luna, RA and Ringel, Y}, title = {Microbiome-Based Diagnostics: Ready for Applications in Laboratory Medicine?.}, journal = {Clinical chemistry}, volume = {63}, number = {11}, pages = {1674-1679}, doi = {10.1373/clinchem.2016.264473}, pmid = {28882888}, issn = {1530-8561}, mesh = {Communicable Diseases/*diagnosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/genetics/physiology ; Humans ; Noncommunicable Diseases/prevention &amp; control/therapy ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA ; }, }
@article {pmid28878075, year = {2017}, author = {Nagashima, S and Takahashi, M and Kobayashi, T and ,  and Nishizawa, T and Nishiyama, T and Primadharsini, PP and Okamoto, H}, title = {Characterization of the Quasi-Enveloped Hepatitis E Virus Particles Released by the Cellular Exosomal Pathway.}, journal = {Journal of virology}, volume = {91}, number = {22}, pages = {}, pmid = {28878075}, issn = {1098-5514}, mesh = {Antibodies, Monoclonal, Murine-Derived/pharmacology ; Capsid Proteins/*metabolism ; Cell Line ; Exosomes/metabolism/*virology ; Hepatitis Antibodies/pharmacology ; Hepatitis E/*metabolism ; Hepatitis E virus/*metabolism ; Humans ; Virus Release/drug effects/*physiology ; }, abstract = {Our previous studies demonstrated that membrane-associated hepatitis E virus (HEV) particles-now considered "quasi-enveloped particles"-are present in the multivesicular body with intraluminal vesicles (exosomes) in infected cells and that the release of HEV virions is related to the exosomal pathway. In this study, we characterized exosomes purified from the culture supernatants of HEV-infected PLC/PRF/5 cells. Purified CD63-, CD9-, or CD81-positive exosomes derived from the culture supernatants of HEV-infected cells that had been cultivated in serum-free medium were found to contain HEV RNA and the viral capsid (ORF2) and ORF3 proteins, as determined by reverse transcription-PCR (RT-PCR) and Western blotting, respectively. Furthermore, immunoelectron microscopy, with or without prior detergent and protease treatment, revealed the presence of virus-like particles in the exosome fraction. These particles were 39.6 ± 1.0 nm in diameter and were covered with a lipid membrane. After treatment with detergent and protease, the diameter of these virus-like particles was 26.9 ± 0.9 nm, and the treated particles became accessible with an anti-HEV ORF2 monoclonal antibody (MAb). The HEV particles in the exosome fraction were capable of infecting naive PLC/PRF/5 cells but were not neutralized by an anti-HEV ORF2 MAb which efficiently neutralizes nonenveloped HEV particles in cell culture. These results indicate that the membrane-wrapped HEV particles released by the exosomal pathway are copurified with the exosomes in the exosome fraction and suggest that the capsids of HEV particles are individually covered by lipid membranes resembling those of exosomes, similar to enveloped viruses.IMPORTANCE Hepatitis E, caused by HEV, is an important infectious disease that is spreading worldwide. HEV infection can cause acute or fulminant hepatitis and can become chronic in immunocompromised hosts, including patients after organ transplantation. The HEV particles present in feces and bile are nonenveloped, while those in circulating blood and culture supernatants are covered with a cellular membrane, similar to enveloped viruses. Furthermore, these membrane-associated and -unassociated HEV particles can be propagated in cultured cells. The significance of our research is that the capsids of HEV particles are individually covered by a lipid membrane that resembles the membrane of exosomes, similar to enveloped viruses, and are released from infected cells via the exosomal pathway. These data will help to elucidate the entry mechanisms and receptors for HEV infection in the future. This is the first report to characterize the detailed morphological features of membrane-associated HEV particles.}, }
@article {pmid28871143, year = {2017}, author = {Cao, H and Liu, X and An, Y and Zhou, G and Liu, Y and Xu, M and Dong, W and Wang, S and Yan, F and Jiang, K and Wang, B}, title = {Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {10322}, pmid = {28871143}, issn = {2045-2322}, mesh = {Adolescent ; Adult ; Animals ; Constipation/diagnosis/*etiology/*metabolism/physiopathology ; Disease Models, Animal ; *Disease Susceptibility ; *Dysbiosis ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Gene Expression ; Humans ; Intestinal Mucosa/metabolism/pathology ; Male ; Mice ; Middle Aged ; RNA, Messenger/genetics ; Serotonin Plasma Membrane Transport Proteins/genetics/*metabolism ; Young Adult ; }, abstract = {Chronic constipation is a prevalent functional gastrointestinal disorder accompanied with intestinal dysbiosis. However, causal relationship between dysbiosis and constipation remains poorly understood. Serotonin transporter (SERT) is a transmembrane transport protein which re-uptakes excessive 5-hydroxytryptamine (5-HT) from effective location to terminate its physiological effects and involves in regulating gastrointestinal motility. In this study, fecal microbiota from patients with constipation and healthy controls were transplanted into the antibiotic depletion mice model. The mice which received fecal microbiota from patients with constipation presented a reducing in intestinal peristalsis and abnormal defecation parameters including the frequency of pellet expulsion, fecal weight and fecal water content. After fecal microbiota transplantation, the SERT expression in the colonic tissue was significantly upregulated, and the content of 5-HT was decreased which negatively correlated with the gastrointestinal transit time. Moverover, fecal microbiota from the mice which received fecal microbiota from patients with constipation also upregulated SERT in Caco-2 cells. Besides, this process accompanied with the decreased abundance of Clostridium, Lactobacillus, Desulfovibrio, and Methylobacterium and an increased tend of Bacteroides and Akkermansia, which also involved in the impairment of intestinal barrier after FMT. Taken together, intestinal dysbiosis may upregulate the SERT expression and contribute to the development of chronic constipation.}, }
@article {pmid28869008, year = {2017}, author = {Rode, AA and Chehri, M and Petersen, AM and Bytzer, P}, title = {[Faecal microbiota transplantation for the treatment of bowel disease].}, journal = {Ugeskrift for laeger}, volume = {179}, number = {31}, pages = {}, pmid = {28869008}, issn = {1603-6824}, mesh = {Clostridium Infections/*therapy ; Denmark ; Donor Selection ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Inflammatory Bowel Diseases/*therapy ; Irritable Bowel Syndrome/*therapy ; Recurrence ; }, abstract = {Faecal microbiota transplantation (FMT) is the transferral of faeces from a healthy donor to a patient with a disease linked to disturbances in the gut microbiota. The treatment has been implemented at several hospitals in Denmark, and banks with frozen donor stool material have been established. The effect of FMT for recurrent Clostridium difficile infection is well-documented. FMT cannot be recommended for routine clinical use for inflammatory bowel disease and irritable bowel syndrome because of lack of data from clinical trials.}, }
@article {pmid28866242, year = {2018}, author = {Walter, J and Maldonado-Gómez, MX and Martínez, I}, title = {To engraft or not to engraft: an ecological framework for gut microbiome modulation with live microbes.}, journal = {Current opinion in biotechnology}, volume = {49}, number = {}, pages = {129-139}, pmid = {28866242}, issn = {1879-0429}, support = {R01 GM099525/GM/NIGMS NIH HHS/United States ; //CIHR/Canada ; }, mesh = {Animals ; Bacteria/*metabolism ; *Ecology ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Strategies aimed at modulating the gut microbiota by using live microbes range from single strains (probiotics or live biotherapeutics) to whole non-defined fecal transplants. Although often clinically efficacious, our understanding on how microbial-based strategies modulate gut microbiome composition and function is vastly incomplete. In this review, we present a framework based on ecological theory that provides mechanistic explanations for the findings obtained in studies that attempted to modulate the gut microbiota of humans and animals using live microbes. We argue that an ecological perspective grounded in theory is necessary to interpret and predict the impact of microbiome-modulating strategies and thus advance our ability to develop improved and targeted approaches with enhanced therapeutic efficiency.}, }
@article {pmid28863010, year = {2017}, author = {Jørgensen, SMD and Hansen, MM and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Faecal microbiota transplantation: establishment of a clinical application framework.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {29}, number = {11}, pages = {e36-e45}, doi = {10.1097/MEG.0000000000000958}, pmid = {28863010}, issn = {1473-5687}, mesh = {Clinical Protocols ; *Clostridioides difficile ; Cryopreservation ; Documentation/standards ; Donor Selection/*standards ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Europe ; *Fecal Microbiota Transplantation ; *Feces/chemistry/microbiology/parasitology ; Forms and Records Control ; Hematologic Tests ; Humans ; Specimen Handling/*standards ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is currently being established as a second-line treatment for recurrent Clostridium difficile infection. FMT is further being considered for other infectious and inflammatory conditions. Safe and reproducible methods for donor screening, laboratory processing and clinical application of FMT are warranted.<br><br>METHODS: Here, we describe the development of a complete clinical application framework for FMT. The framework has been developed to comply with the European Tissue Act, thus considering donor faeces for FMT comparable to a human tissue and not a drug.<br><br>RESULTS: Recruitment and screening of potential faeces donors took place in the public blood donor setting and consisted of questionnaires, blood sampling and faecal sample analysis. Once approved, and following their written informed consent, eligible donors were invited for voluntary faecal donation. Laboratory processing protocols describe the initial handling, cryopreservation and thawing for clinical application. The clinical FMT procedures took place in a gastroenterological setting using a nasojejunal tube or colonoscopy, and follow-ups were performed at 1, 8 and 26 weeks after FMT. Complete traceability of essential equipment, faecal samples and donor-recipient matching data will be maintained and secured for 30 years.<br><br>CONCLUSION: A clinical FMT service should be consolidated by a complete documentation system that complies with the European Tissue Act. In this paper, we provide a description of such a framework.}, }
@article {pmid28862999, year = {2017}, author = {Romaní-Pérez, M and Agusti, A and Sanz, Y}, title = {Innovation in microbiome-based strategies for promoting metabolic health.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {20}, number = {6}, pages = {484-491}, doi = {10.1097/MCO.0000000000000419}, pmid = {28862999}, issn = {1473-6519}, mesh = {Animals ; Bacteroides ; *Diet ; Disease Management ; Disease Models, Animal ; Eubacterium ; Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Membrane Proteins/metabolism ; Obesity/therapy ; *Probiotics ; }, abstract = {PURPOSE OF REVIEW: Update on the development of microbiome-based interventions and dietary supplements to combat obesity and related comorbidities, which are leading causes of global mortality.<br><br>RECENT FINDINGS: The role of intestinal dysbiosis, partly resulting from unhealthy diets, in the development of obesity and metabolic disorders, is well documented by recent translational research. Human experimental trials with whole-faecal transplants are ongoing, and their results will be crucial as proof of concept that interventions intended to modulate the microbiome composition and function could be alternatives for the management of obesity and related comorbidities. Potential next-generation probiotic bacteria (Akkermansia, Bacteroides spp., Eubacterium halli) and microbiota-derived molecules (e.g. membrane proteins, short-chain fatty acids) are being evaluated in preclinical and clinical trials to promote the development of innovative dietary supplements. The fact that live or inactivated bacteria and their products can regulate pathways that increase energy expenditure, and reduce energy intake, and absorption and systemic inflammation make them attractive research targets from a nutritional and clinical perspective.<br><br>SUMMARY: Understanding which are the beneficial bacteria and their bioactive products is helping us to envisage innovative microbiome-based dietary interventions to tackle obesity. Advances will likely result from future refinements of these strategies according to the individual's microbiome configuration and its particular response to interventions, thereby progressing towards personalized nutrition.}, }
@article {pmid28862530, year = {2018}, author = {Allen, JM and Mailing, LJ and Cohrs, J and Salmonson, C and Fryer, JD and Nehra, V and Hale, VL and Kashyap, P and White, BA and Woods, JA}, title = {Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice.}, journal = {Gut microbes}, volume = {9}, number = {2}, pages = {115-130}, pmid = {28862530}, issn = {1949-0984}, mesh = {Animals ; Body Weight ; Cecum/metabolism/*microbiology ; Colitis/chemically induced/*prevention &amp; control ; Colon/anatomy &amp; histology/*immunology/pathology ; Cytokines/genetics ; Dextran Sulfate/administration &amp; dosage ; Disease Models, Animal ; Fatty Acids, Volatile/analysis ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Gene Expression Regulation/immunology ; Germ-Free Life ; Homeostasis/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Physical Conditioning, Animal/*physiology ; Sex Factors ; }, abstract = {Exercise reduces the risk of inflammatory disease by modulating a variety of tissue and cell types, including those within the gastrointestinal tract. Recent data indicates that exercise can also alter the gut microbiota, but little is known as to whether these changes affect host function. Here, we use a germ-free (GF) animal model to test whether exercise-induced modifications in the gut microbiota can directly affect host responses to microbiota colonization and chemically-induced colitis. Donor mice (n = 19) received access to a running wheel (n = 10) or remained without access (n = 9) for a period of six weeks. After euthanasia, cecal contents were pooled by activity treatment and transplanted into two separate cohorts of GF mice. Two experiments were then conducted. First, mice were euthanized five weeks after the microbiota transplant and tissues were collected for analysis. A second cohort of GF mice were colonized by donor microbiotas for four weeks before dextran-sodium-sulfate was administered to induce acute colitis, after which mice were euthanized for tissue analysis. We observed that microbial transplants from donor (exercised or control) mice led to differences in microbiota β-diversity, metabolite profiles, colon inflammation, and body mass in recipient mice five weeks after colonization. We also demonstrate that colonization of mice with a gut microbiota from exercise-trained mice led to an attenuated response to chemical colitis, evidenced by reduced colon shortening, attenuated mucus depletion and augmented expression of cytokines involved in tissue regeneration. Exercise-induced modifications in the gut microbiota can mediate host-microbial interactions with potentially beneficial outcomes for the host.}, }
@article {pmid28859349, year = {2017}, author = {Lagier, JC and Aubry, C and Delord, M and Michelet, P and Tissot-Dupont, H and Million, M and Brouqui, P and Raoult, D and Parola, P}, title = {From Expert Protocols to Standardized Management of Infectious Diseases.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {suppl_1}, pages = {S12-S19}, doi = {10.1093/cid/cix403}, pmid = {28859349}, issn = {1537-6591}, mesh = {Administration, Oral ; Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; *Antimicrobial Stewardship ; Clinical Protocols ; Clostridioides difficile/drug effects/isolation &amp; purification ; Clostridium Infections/therapy ; *Communicable Disease Control/methods ; Coxiella burnetii/drug effects/isolation &amp; purification ; *Disease Management ; Endocarditis, Bacterial/drug therapy/epidemiology ; Fecal Microbiota Transplantation ; France/epidemiology ; Humans ; *Infection Control ; Q Fever/epidemiology/therapy ; }, abstract = {We report here 4 examples of management of infectious diseases (IDs) at the University Hospital Institute Méditerranée Infection in Marseille, France, to illustrate the value of expert protocols feeding standardized management of IDs. First, we describe our experience on Q fever and Tropheryma whipplei infection management based on in vitro data and clinical outcome. Second, we describe our management-based approach for the treatment of infective endocarditis, leading to a strong reduction of mortality rate. Third, we report our use of fecal microbiota transplantation to face severe Clostridium difficile infections and to perform decolonization of patients colonized by emerging highly resistant bacteria. Finally, we present the standardized management of the main acute infections in patients admitted in the emergency department, promoting antibiotics by oral route, checking compliance with the protocol, and avoiding the unnecessary use of intravenous and urinary tract catheters. Overall, the standardization of the management is the keystone to reduce both mortality and morbidity related to IDs.}, }
@article {pmid28858247, year = {2017}, author = {Indrio, F and Riezzo, G and Tafuri, S and Ficarella, M and Carlucci, B and Bisceglia, M and Polimeno, L and Francavilla, R}, title = {Probiotic Supplementation in Preterm: Feeding Intolerance and Hospital Cost.}, journal = {Nutrients}, volume = {9}, number = {9}, pages = {}, pmid = {28858247}, issn = {2072-6643}, mesh = {Cytokines/chemistry/genetics/metabolism ; Double-Blind Method ; Feces/chemistry ; Female ; Gastrointestinal Motility/*drug effects ; Gene Expression Regulation ; Health Care Costs ; Humans ; Infant, Newborn ; Infant, Premature ; *Limosilactobacillus reuteri ; Length of Stay ; Male ; Probiotics/*economics/*pharmacology ; }, abstract = {We hypothesized that giving the probiotic strain Lactobacillus reuteri (L. reuteri) DSM 17938 to preterm, formula-fed infants would prevent an early traumatic intestinal inflammatory insult modulating intestinal cytokine profile and reducing the onset of feeding intolerance. Newborn were randomly allocated during the first 48 h of life to receive either daily probiotic (10[8] colony forming units (CFUs) of L. reuteri DSM 17938) or placebo for one month. All the newborns underwent to gastric ultrasound for the measurement of gastric emptying time. Fecal samples were collected for the evaluation of fecal cytokines. Clinical data on feeding intolerance and weight gain were collected. The costs of hospital stays were calculated. The results showed that the newborns receiving L. reuteri DSM 17938 had a significant decrease in the number of days needed to reach full enteral feeding (p < 0.01), days of hospital stay (p < 0.01), and days of antibiotic treatment (p < 0.01). Statistically significant differences were observed in pattern of fecal cytokine profiles. The anti-inflammatory cytokine interleukin (IL)-10, was increased in newborns receiving L. reuteri DSM 17938. Pro-inflammatory cytokines: IL-17, IL-8, and tumor necrosis factor (TNF)-alpha levels were increased in newborns given placebo. Differences in the gastric emptying and fasting antral area (FAA) were also observed. Our study demonstrates an effective role for L. reuteri DSM 17938 supplementation in preventing feeding intolerance and improving gut motor and immune function development in bottle-fed stable preterm newborns. Another benefit from the use of probiotics is the reducing cost for the Health Care service.}, }
@article {pmid28858073, year = {2017}, author = {Allegretti, J and Eysenbach, LM and El-Nachef, N and Fischer, M and Kelly, C and Kassam, Z}, title = {The Current Landscape and Lessons from Fecal Microbiota Transplantation for Inflammatory Bowel Disease: Past, Present, and Future.}, journal = {Inflammatory bowel diseases}, volume = {23}, number = {10}, pages = {1710-1717}, doi = {10.1097/MIB.0000000000001247}, pmid = {28858073}, issn = {1536-4844}, mesh = {Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Forecasting ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*complications/microbiology/*therapy ; Randomized Controlled Trials as Topic ; }, abstract = {Fecal microbiota transplantation (FMT) has changed the standard of care for Clostridium difficile infection. However, there is limited data focusing on efficacy and safety profile of FMT in patients with C. difficile infection with underlying inflammatory bowel disease (IBD), including the risk of IBD flare. Recently, there is also emerging evidence supporting the role of FMT to treat IBD including promising randomized trials in ulcerative colitis. However, with heterogeneity across these studies, the clinical application of this emerging therapy has yet to be fully elucidated. Here, we aim to review the current landscape of this rapidly developing field, mapping the efficacy and safety of FMT (1) to treat C. difficile infection in patients with IBD, (2) to treat underlying IBD, and (3) outline ongoing clinical trials and the future of the microbiome space.}, }
@article {pmid28852524, year = {2017}, author = {Lan, N and Ashburn, J and Shen, B}, title = {Fecal microbiota transplantation for Clostridium difficile infection in patients with ileal pouches.}, journal = {Gastroenterology report}, volume = {5}, number = {3}, pages = {200-207}, pmid = {28852524}, issn = {2052-0034}, abstract = {Background:Clostridium difficile infection (CDI) in patients with ileal pouch-anal anastomosis (IPAA) has been increasingly recognized. The aim of this study was to evaluate the outcome of fecal microbiota transplantation (FMT) in patients with pouch and CDI. Methods: All consecutive patients that underwent FMT for CDI from 2012 to 2016 were extracted from our IRB-approved, prospectively maintained Registry of Pouch Disorders. The primary outcome was negative stool tests for Clostridium difficile after FMT and the secondary outcomes were symptomatic and endoscopic responses. Results: A total of 13 patients were included in this study, with 10 being Caucasian males (76.9%). All patients had underlying ulcerative colitis for J pouch surgery. After a mean of 2.8±0.8 courses of antibiotic treatments was given and failed, 22 sessions of FMT were administered with an average of 1.7±1.1 sessions each. Within the 22 sessions, 16 were given via pouchoscopy, 4 via esophagogastroduodenoscopy and 2 via enemas. All patients tested negative on C. difficile polymerase chain reaction (PCR) after the initial FMT with a total of 7/12 (58.3%) documented patients showed symptomatic improvements and 3/11 (27.3%) patients showed endoscopic improvement according to the modified Pouchitis Disease Activity Index. During the follow-up of 1.2±1.1 years, there were a total of five patients (38.5%) that had recurrence after the successful initial treatment and four of them were successfully treated again with FMT. Conclusions: FMT appeared to be effective in eradication of CDI in patients with ileal pouches. However, FMT had a modest impact on endoscopic inflammation and recurrence after FMT and recurrence was common.}, }
@article {pmid28852308, year = {2017}, author = {Cenit, MC and Sanz, Y and Codoñer-Franch, P}, title = {Influence of gut microbiota on neuropsychiatric disorders.}, journal = {World journal of gastroenterology}, volume = {23}, number = {30}, pages = {5486-5498}, pmid = {28852308}, issn = {2219-2840}, mesh = {Animals ; Brain/growth &amp; development/*physiopathology ; DNA Methylation ; Disease Models, Animal ; Epigenesis, Genetic ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Hypothalamo-Hypophyseal System/physiopathology ; Neurodegenerative Diseases/*etiology/prevention &amp; control ; Neurodevelopmental Disorders/*etiology/prevention &amp; control ; Pituitary-Adrenal System/physiopathology ; Stress, Psychological/*complications/physiopathology ; }, abstract = {The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson's disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gut microbiota transplantation can transfer a behavioral phenotype, suggesting that the gut microbiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gut microbiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors, and the possible microbiota-targeted intervention strategies that could improve health status and prevent psychiatric disorders in the near future.}, }
@article {pmid28852307, year = {2017}, author = {Guariso, G and Gasparetto, M}, title = {Treating children with inflammatory bowel disease: Current and new perspectives.}, journal = {World journal of gastroenterology}, volume = {23}, number = {30}, pages = {5469-5485}, pmid = {28852307}, issn = {2219-2840}, mesh = {Age Factors ; Biological Products/pharmacology/*therapeutic use ; Biosimilar Pharmaceuticals/pharmacology/therapeutic use ; Child ; Clinical Trials as Topic ; Colitis, Ulcerative/immunology/*therapy ; Crohn Disease/immunology/*therapy ; Diet Therapy/methods ; Fecal Microbiota Transplantation/*methods/trends ; Gastrointestinal Microbiome/immunology ; Humans ; Immunosuppression Therapy/methods/trends ; Immunosuppressive Agents/pharmacology/*therapeutic use ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gut characterised by alternating periods of remission and relapse. Whilst the mechanism underlying this disease is yet to be fully understood, old and newer generation treatments can only target selected pathways of this complex inflammatory process. This narrative review aims to provide an update on the most recent advances in treatment of paediatric IBD. A MEDLINE search was conducted using "paediatric inflammatory bowel disease", "paediatric Crohn's disease", "paediatric ulcerative colitis", "treatment", "therapy", "immunosuppressant", "biologic", "monitoring" and "biomarkers" as key words. Clinical trials, systematic reviews, and meta-analyses published between 2014 and 2016 were selected. Studies referring to earlier periods were also considered in case the data was relevant to our scope. Major advances have been achieved in monitoring the individual metabolism, toxicity and response to relevant medications in IBD including thiopurines and biologics. New biologics acting on novel mechanisms such as selective interference with lymphocyte trafficking are emerging treatment options. Current research is investing in the development of reliable prognostic biomarkers, aiming to move towards personalised treatments targeted to individual patients.}, }
@article {pmid28848361, year = {2017}, author = {Hughes, T and O'Connor, T and Techasen, A and Namwat, N and Loilome, W and Andrews, RH and Khuntikeo, N and Yongvanit, P and Sithithaworn, P and Taylor-Robinson, SD}, title = {Opisthorchiasis and cholangiocarcinoma in Southeast Asia: an unresolved problem.}, journal = {International journal of general medicine}, volume = {10}, number = {}, pages = {227-237}, pmid = {28848361}, issn = {1178-7074}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {The prevalence of cholangiocarcinoma (CCA) in Southeast Asia is much higher than other areas of the world. Eating raw, fermented, or undercooked cyprinid fish, infected with the liver fluke, Opisthorchis viverrini sensu lato (sl), results in chronic biliary inflammation, periductal fibrosis, and increased cancer risk. There may be associated glomerulonephritis. The process of infection is difficult to disrupt because eating practices have proven extremely difficult to change, and the life cycle of the fluke cannot be broken due to high prevalence in canine and feline reservoir hosts. Fecal analysis and enzyme-linked immunosorbent assay tests can be used to diagnose opisthorchiasis. Diagnosis of CCA is complex, partly due to the lack of definitive imaging characteristics but also due to the difficulty of obtaining samples for cytology or histology. This cancer has proven to be resistant to common chemotherapy treatments and so the two avenues of treatment available are surgical resection and liver transplantation, both requiring early detection of the tumor for the best chances of success. Late presentation of symptoms reduces the chances of successful surgical intervention. While liver fluke infections can be treated with praziquantel, individuals will often become reinfected, and multiple reinfections can be more harmful than a singular, long-term infection. A key research on the detection and characterization of novel biomarkers in all parts of the carcinogenic pathway for early diagnosis is needed.}, }
@article {pmid28844808, year = {2017}, author = {Torres-Fuentes, C and Schellekens, H and Dinan, TG and Cryan, JF}, title = {The microbiota-gut-brain axis in obesity.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {2}, number = {10}, pages = {747-756}, doi = {10.1016/S2468-1253(17)30147-4}, pmid = {28844808}, issn = {2468-1253}, mesh = {Affect ; Appetite Regulation ; Brain/*metabolism ; Diet, Reducing ; Energy Metabolism ; Fecal Microbiota Transplantation ; Feeding Behavior/psychology ; *Gastrointestinal Microbiome ; Humans ; Metagenomics ; Obesity/*metabolism/psychology/therapy ; Prebiotics ; Probiotics/therapeutic use ; Reward ; }, abstract = {Changes in microbial diversity and composition are increasingly associated with several disease states including obesity and behavioural disorders. Obesity-associated microbiota alter host energy harvesting, insulin resistance, inflammation, and fat deposition. Additionally, intestinal microbiota can regulate metabolism, adiposity, homoeostasis, and energy balance as well as central appetite and food reward signalling, which together have crucial roles in obesity. Moreover, some strains of bacteria and their metabolites might target the brain directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms. Therefore, the gut microbiota is becoming a target for new anti-obesity therapies. Further investigations are needed to elucidate the intricate gut-microbiota-host relationship and the potential of gut-microbiota-targeted strategies, such as dietary interventions and faecal microbiota transplantation, as promising metabolic therapies that help patients to maintain a healthy weight throughout life.}, }
@article {pmid28843904, year = {2017}, author = {Sünderhauf, A and Skibbe, K and Preisker, S and Ebbert, K and Verschoor, A and Karsten, CM and Kemper, C and Huber-Lang, M and Basic, M and Bleich, A and Büning, J and Fellermann, K and Sina, C and Derer, S}, title = {Regulation of epithelial cell expressed C3 in the intestine - Relevance for the pathophysiology of inflammatory bowel disease?.}, journal = {Molecular immunology}, volume = {90}, number = {}, pages = {227-238}, doi = {10.1016/j.molimm.2017.08.003}, pmid = {28843904}, issn = {1872-9142}, mesh = {Animals ; Bacteria/immunology ; Cell Line ; Colitis, Ulcerative/chemically induced/*pathology ; Complement C3a/*biosynthesis/metabolism ; Complement C3b/*biosynthesis/metabolism ; Dextran Sulfate/toxicity ; Epithelial Cells/*metabolism ; Humans ; Inflammation/pathology ; Intestinal Mucosa/immunology/*pathology ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred C57BL ; Signal Transduction/immunology ; Toll-Like Receptor 1/biosynthesis ; Toll-Like Receptor 2/biosynthesis ; Toll-Like Receptor 4/biosynthesis ; }, abstract = {The complement system not only plays a critical role in efficient detection and clearance of bacteria, but also in intestinal immune homeostasis as mice deficient for key complement components display enhanced intestinal inflammation upon experimental colitis. Because underlying molecular mechanisms for this observation are unclear, we investigated the crosstalk between intestinal epithelial cells (IEC), bacteria and the complement system in the course of chronic colitis. Surprisingly, mouse intestinal epithelial cell lines constitutively express high mRNA levels of complement component 3 (C3), Toll-like receptor 2 (Tlr2) and Tlr4. Stimulation of these cells with lipopolysaccharide (LPS), but not with flagellin, LD-muramyldipeptide or peptidoglycan, triggered increased C3 expression, secretion and activation. Stimulation of the C3aR on these cell lines with C3a resulted in an increase of LPS-triggered pro-inflammatory response. Tissue biopsies from C57BL/6J mice revealed higher expression of C3, Tlr1, Tlr2 and Tlr4 in colonic primary IECs (pIECs) compared to ileal pIECs, while in germ-free mice no differences in C3 protein expression was observed. In DSS-induced chronic colitis mouse models, C3 mRNA expression was upregulated in colonic biopsies and ileal pIECs with elevated C3 protein in the lamina propria, IECs and the mucus. Notably, increased C3b opsonization of mucosa-attached bacteria and decreased fecal full-length C3 protein was observed in DSS-treated compared to untreated mice. Of significant interest, non-inflamed and inflamed colonic biopsy samples from CD but not UC patients displayed exacerbated C3 expression compared to controls. These findings suggest that a novel TLR4-C3 axis could control the intestinal immune response during chronic colitis.}, }
@article {pmid28840819, year = {2017}, author = {Collins, FL and Rios-Arce, ND and Schepper, JD and Parameswaran, N and McCabe, LR}, title = {The Potential of Probiotics as a Therapy for Osteoporosis.}, journal = {Microbiology spectrum}, volume = {5}, number = {4}, pages = {}, pmid = {28840819}, issn = {2165-0497}, support = {P30 DK020572/DK/NIDDK NIH HHS/United States ; R01 AT007695/AT/NCCIH NIH HHS/United States ; R01 DK101050/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bone Density ; Bone Remodeling/*physiology ; Bone and Bones ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Female ; Fractures, Bone/*prevention &amp; control ; Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Osteoporosis/pathology/prevention &amp; control/*therapy ; Probiotics/*therapeutic use ; }, abstract = {Osteoporosis, characterized by low bone mass and micro-architectural deterioration of bone tissue with increased risk of fracture, can be categorized into two forms: primary and secondary, depending on whether it occurs as part of the natural aging process (estrogen deficiency) or as part of disease pathology. In both forms bone loss is due to an imbalance in the bone remodeling process, with resorption/formation skewed more toward bone loss. Recent studies and emerging evidence consistently demonstrate the potential of the intestinal microbiota to modulate bone health. This review discusses the process of bone remodeling and the pathology of osteoporosis and introduces the intestinal microbiota and its potential to influence bone health. In particular, we highlight recent murine studies that examine how probiotic supplementation can both increase bone density in healthy individuals and protect against primary (estrogen deficiency) as well as secondary osteoporosis. Potential mechanisms are described to account for how probiotic treatments could be exerting their beneficial effect on bone health.}, }
@article {pmid28840809, year = {2017}, author = {Bakker, GJ and Nieuwdorp, M}, title = {Fecal Microbiota Transplantation: Therapeutic Potential for a Multitude of Diseases beyond Clostridium difficile.}, journal = {Microbiology spectrum}, volume = {5}, number = {4}, pages = {}, pmid = {28840809}, issn = {2165-0497}, mesh = {Diabetes Mellitus, Type 2/microbiology/*therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/microbiology ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Non-alcoholic Fatty Liver Disease/microbiology/*therapy ; }, abstract = {The human intestinal tract contains trillions of bacteria, collectively called the gut microbiota. Recent insights have linked the gut microbiota to a plethora of diseases, including Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), and metabolic diseases such as obesity, type 2 diabetes (T2D), and nonalcoholic steatohepatitis (NASH). Fecal microbiota transplantation (FMT) is currently tested as a therapeutic option in various diseases and can also help to dissect association from causality with respect to gut microbiota and disease. In CDI, FMT has been shown to be superior to antibiotic treatment. For IBD, T2D, and NASH, several placebo-controlled randomized controlled trials are under way. Moreover, techniques and standardization are developing. With the extension of FMT as a treatment modality in diseases other than CDI, a whole new treatment option may be emerging. Moreover, correlating alterations in specific strains to disease outcome may prove pivotal in finding new bacterial targets. Thus, although causality of the gut microbiota in various diseases still needs to be proven, FMT may prove to be a powerful tool providing us with diagnostic and therapeutic leads.}, }
@article {pmid28840580, year = {2017}, author = {Kelly, CR and Allegretti, JR}, title = {FMT in IBD: What Have We Learned?.}, journal = {Digestive diseases and sciences}, volume = {62}, number = {10}, pages = {2618-2620}, pmid = {28840580}, issn = {1573-2568}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases ; }, }
@article {pmid28838410, year = {2017}, author = {Khanna, S and Raffals, LE}, title = {The Microbiome in Crohn's Disease: Role in Pathogenesis and Role of Microbiome Replacement Therapies.}, journal = {Gastroenterology clinics of North America}, volume = {46}, number = {3}, pages = {481-492}, doi = {10.1016/j.gtc.2017.05.004}, pmid = {28838410}, issn = {1558-1942}, mesh = {Crohn Disease/complications/immunology/*microbiology/therapy ; Diet Therapy ; Dysbiosis/complications/*microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; Humans ; Immunity, Mucosal/immunology ; Probiotics/therapeutic use ; }, abstract = {Individuals with a genetic predisposition to Crohn's disease develop aberrant immune responses to environmental triggers. The gastrointestinal microbiota is increasingly recognized to play an important role in the development of Crohn's disease. Decrease in global gut microbial diversity and specific bacterial alterations have been implicated in Crohn's disease. Advances in sequencing techniques and bioinformatics and correlation with host genetics continue to improve insight into the structure and function of the microbial community and interactions with the host immune system. This article summarizes the existing literature on the role of the gut microbiome and its manipulation in the development and management of Crohn's disease.}, }
@article {pmid28832994, year = {2017}, author = {Nissilä, E and Korpela, K and Lokki, AI and Paakkanen, R and Jokiranta, S and de Vos, WM and Lokki, ML and Kolho, KL and Meri, S}, title = {C4B gene influences intestinal microbiota through complement activation in patients with paediatric-onset inflammatory bowel disease.}, journal = {Clinical and experimental immunology}, volume = {190}, number = {3}, pages = {394-405}, pmid = {28832994}, issn = {1365-2249}, mesh = {Adolescent ; Child ; Child, Preschool ; *Colitis, Ulcerative/genetics/immunology/microbiology/pathology ; *Complement Activation/genetics/immunology ; *Complement C4b/genetics/immunology ; Complement Membrane Attack Complex/genetics/immunology ; *Crohn Disease/genetics/immunology/microbiology/pathology ; Female ; Gastrointestinal Microbiome/*immunology ; Gene Dosage/*immunology ; Humans ; Male ; Yersinia pseudotuberculosis/immunology ; }, abstract = {Complement C4 genes are linked to paediatric inflammatory bowel disease (PIBD), but the mechanisms have remained unclear. We examined the influence of C4B gene number on intestinal microbiota and in-vitro serum complement activation by intestinal microbes in PIBD patients. Complement C4A and C4B gene numbers were determined by genomic reverse transcription-polymerase chain reaction (RT-PCR) from 64 patients with PIBD (Crohn's disease or ulcerative colitis). The severity of the disease course was determined from faecal calprotectin levels. Intestinal microbiota was assessed using the HITChip microarray. Complement reactivity in patients was analysed by incubating their sera with Yersinia pseudotuberculosis and Akkermansia muciniphila and determining the levels of C3a and soluble terminal complement complex (SC5b-9) using enzyme immunoassays. The microbiota diversity was wider in patients with no C4B genes than in those with one or two C4B genes, irrespective of intestinal inflammation. C4B and total C4 gene numbers correlated positively with soluble terminal complement complex (TCC, SC5b-9) levels when patient serum samples were stimulated with bacteria. Our results suggest that the C4B gene number associates positively with inflammation in patients with PIBD. Multiple copies of the C4B gene may thus aggravate the IBD-associated dysbiosis through escalated complement reactivity towards the microbiota.}, }
@article {pmid28827811, year = {2017}, author = {Moss, EL and Falconer, SB and Tkachenko, E and Wang, M and Systrom, H and Mahabamunuge, J and Relman, DA and Hohmann, EL and Bhatt, AS}, title = {Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0182585}, pmid = {28827811}, issn = {1932-6203}, support = {K08 CA184420/CA/NCI NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/classification ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; *Immunocompromised Host ; Male ; Middle Aged ; Treatment Outcome ; }, abstract = {Immunocompromised individuals are at high risk of developing Clostridium difficile-associated disease (CDAD). Fecal microbiota transplantation (FMT) is a highly effective therapy for refractory or recurrent CDAD and, despite safety concerns, has recently been offered to immunocompromised patients. We investigated the genomics of bacterial composition following FMT in immunocompromised patients over a 1-year period. Metagenomic, strain and gene-level bacterial dynamics were characterized in two CDAD-affected hematopoietic stem cell (HCT) recipients following FMT. We found alterations in gene content, including loss of virulence and antibiotic resistance genes. These alterations were accompanied by long-term bacterial divergence at the species and strain levels. Our findings suggest limited durability of the specific bacterial consortium introduced with FMT and indicate that alterations of the functional potential of the microbiome are more complex than can be inferred by taxonomic information alone. Our observation that FMT alone cannot induce long-term donor-like alterations of the microbiota of HCT recipients suggests that FMT cannot indefinitely supersede environmental and/or host factors in shaping bacterial composition.}, }
@article {pmid28827258, year = {2017}, author = {Pai, N and Popov, J}, title = {Protocol for a randomised, placebo-controlled pilot study for assessing feasibility and efficacy of faecal microbiota transplantation in a paediatric ulcerative colitis population: PediFETCh trial.}, journal = {BMJ open}, volume = {7}, number = {8}, pages = {e016698}, pmid = {28827258}, issn = {2044-6055}, mesh = {Adolescent ; Biomarkers/*analysis ; Canada ; Child ; Child, Preschool ; Colitis, Ulcerative/*therapy ; Feasibility Studies ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Pilot Projects ; Recurrence ; Research Design ; Single-Blind Method ; Treatment Outcome ; }, abstract = {INTRODUCTION: Ulcerative colitis (UC) is a chronic, relapsing condition characterised by colonic inflammation. Increasing prevalence in early-age diagnosis provides opportunities for additional complications in later life as a result of prolonged exposure to inflammatory and therapeutic insults, necessitating novel avenues for therapeutics which may result in fewer side effects. Faecal microbiota transplantation (FMT) has previously demonstrated potential therapeutic benefit in an adult randomised-controlled trial and several recurrent Clostridium difficile infection studies. This phase Ib pilot will be the first randomised, single-blinded, placebo-controlled trial to assess feasibility and patient outcomes in a paediatric inflammatory bowel disease (IBD) population.<br><br>METHODS AND ANALYSIS: Fifty patients will be randomised 1:1 to receive normal saline control or active sample. Enema administrations will be performed two times per week for 6&#x2009;weeks, followed at a 6-month follow-up period. Feasibility outcomes will include measures of patient eligibility, recruitment, willingness to participate, samples collections, hospitalizations and drop-out rate. Improvements in disease symptoms will determine the efficacy of treatment. Clinical disease scores will be taken throughout the study period using the Paediatric Ulcerative Colitis Activity Index (PUCAI). Monitoring of inflammatory markers in blood and stool will be performed at regular intervals. Microbiome analysis will be conducted on stool samples collected throughout the trials period. Imaging and endoscopic surveillance will be conducted if clinically necessary.<br><br>ETHICS AND DISSEMINATION: Ethics was obtained from local hospital research ethics boards across all three sites. Health Canada and FDA approval was obtained for the use of an Investigatory New Drug product. Results from this trial will be presented in international conferences and published in peer-review journals.<br><br>TRIAL REGISTRATION NUMBER: Trial registration number: NCT02487238; preresults.}, }
@article {pmid28823860, year = {2017}, author = {Wong, SH and Zhao, L and Zhang, X and Nakatsu, G and Han, J and Xu, W and Xiao, X and Kwong, TNY and Tsoi, H and Wu, WKK and Zeng, B and Chan, FKL and Sung, JJY and Wei, H and Yu, J}, title = {Gavage of Fecal Samples From Patients With Colorectal Cancer Promotes Intestinal Carcinogenesis in Germ-Free and Conventional Mice.}, journal = {Gastroenterology}, volume = {153}, number = {6}, pages = {1621-1633.e6}, doi = {10.1053/j.gastro.2017.08.022}, pmid = {28823860}, issn = {1528-0012}, mesh = {Animals ; Azoxymethane ; Case-Control Studies ; Cell Proliferation ; *Cell Transformation, Neoplastic/metabolism/pathology ; Colon/metabolism/*microbiology/pathology ; Colonic Polyps/chemically induced/metabolism/*microbiology/pathology ; Colorectal Neoplasms/chemically induced/metabolism/*microbiology/pathology ; Disease Models, Animal ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Gene Expression Regulation, Neoplastic ; Germ-Free Life ; Host-Pathogen Interactions ; Humans ; Inflammation Mediators/metabolism ; Ki-67 Antigen/metabolism ; Lymphocytes, Tumor-Infiltrating/metabolism/microbiology ; Male ; Mice, Inbred C57BL ; Th1 Cells/metabolism/microbiology ; Th17 Cells/metabolism/microbiology ; }, abstract = {BACKGROUND &amp; AIMS: Altered gut microbiota is implicated in development of colorectal cancer (CRC). Some intestinal bacteria have been reported to potentiate intestinal carcinogenesis by producing genotoxins, altering the immune response and intestinal microenvironment, and activating oncogenic signaling pathways. We investigated whether stool from patients with CRC could directly induce colorectal carcinogenesis in mice.<br><br>METHODS: We obtained stored stool samples from participants in a metagenome study performed in Hong Kong. Conventional (male C57BL/6) mice were given azoxymethane to induce colon neoplasia after receiving a course of antibiotics in drinking water. Mice were gavaged twice weekly with stool from 5 patients with CRC or 5 healthy individuals (controls) for 5 weeks. Germ-free C57BL/6 mice were gavaged once with stool from 5 patients with CRC or 5 controls. We collected intestinal tissues from mice and performed histology, immunohistochemistry, expression microarray, quantitative polymerase chain reaction, immunoblot, and flow cytometry analyses. We performed 16S ribosomal RNA gene sequencing analysis of feces from mice.<br><br>RESULTS: Significantly higher proportions of conventional mice fed with stool from individuals with CRC than control stool developed high-grade dysplasia (P < .05) and macroscopic polyps (P < .01). We&#xa0;observed a higher proportion of proliferating (Ki-67-positive) cells in colons of germ-free mice fed with stool from&#xa0;patients with CRC vs those fed with stool from controls (P&#xa0;< .05). Feces from germ-free and conventional mice fed with stool from patients with CRC vs controls contained different microbial compositions, with lower richness in mice fed with stool from patients with CRC. Intestines collected from conventional and germ-free mice fed with stool from patients with CRC had increased expression of cytokines that modulate inflammation, including C-X-C motif chemokine receptor 1, C-X-C motif chemokine receptor 2, interleukin 17A (IL17A), IL22, and IL23A. Intestines from conventional and germ-free mice fed with stool from patients with CRC contained higher proportions of T-helper 1 (Th1) cells (2.25% vs 0.44%) and&#xa0;Th17 cells (2.08% vs 0.31%) (P < .05 for each) than mice fed with stool from controls. Real-time polymerase chain reaction arrays revealed up-regulation of genes involved in cell proliferation, stemness, apoptosis, angiogenesis, invasiveness, and metastasis in mice fed with stool from patients with CRC.<br><br>CONCLUSIONS: We fed stool samples from patients with CRC and heathy individuals to germ-free mice and conventional mice with azoxymethane. We found stool from patients with CRC to increase the numbers of polyps, levels of intestinal dysplasia and proliferation, markers of inflammation, and proportions of Th1 and Th17 cells in colon, compared with stool from individuals without CRC. This study provides evidence that the fecal microbiota from patients with CRC can promote tumorigenesis in germ-free mice and mice given a carcinogen.}, }
@article {pmid28814217, year = {2017}, author = {Razik, R and Osman, M and Lieberman, A and Allegretti, JR and Kassam, Z}, title = {Faecal microbiota transplantation for &lt;em&gt;Clostridium difficile&lt;/em&gt; infection: a multicentre study of non-responders.}, journal = {The Medical journal of Australia}, volume = {207}, number = {4}, pages = {159-160}, doi = {10.5694/mja16.01452}, pmid = {28814217}, issn = {1326-5377}, mesh = {Aged ; Aged, 80 and over ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; *Guideline Adherence ; Humans ; Male ; Middle Aged ; Netherlands ; Prospective Studies ; Proton Pump Inhibitors/administration &amp; dosage ; Recurrence ; Risk Factors ; Treatment Failure ; Treatment Outcome ; United States ; }, }
@article {pmid28814214, year = {2017}, author = {Brandt, LJ}, title = {Faecal microbiota transplantation: past, present and future.}, journal = {The Medical journal of Australia}, volume = {207}, number = {4}, pages = {151-152}, doi = {10.5694/mja17.00372}, pmid = {28814214}, issn = {1326-5377}, mesh = {Clostridioides difficile ; *Fecal Microbiota Transplantation ; *Feces ; Gastrointestinal Microbiome ; }, }
@article {pmid28814204, year = {2017}, author = {Moayyedi, P and Yuan, Y and Baharith, H and Ford, AC}, title = {Faecal microbiota transplantation for &lt;em&gt;Clostridium difficile&lt;/em&gt;-associated diarrhoea: a systematic review of randomised controlled trials.}, journal = {The Medical journal of Australia}, volume = {207}, number = {4}, pages = {166-172}, doi = {10.5694/mja17.00295}, pmid = {28814204}, issn = {1326-5377}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; Diarrhea/microbiology/*therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Randomized Controlled Trials as Topic ; Vancomycin/therapeutic use ; }, abstract = {OBJECTIVES: Faecal microbiota transplantation (FMT) has emerged as a useful approach for treating Clostridium difficile-associated diarrhoea (CDAD). Randomised controlled trials (RCTs) have recently evaluated its effectiveness, but systematic reviews have focused on evidence from case series. We therefore conducted a systematic review and meta-analysis of RCTs evaluating the effectiveness of FMT for treating CDAD.<br><br>STUDY DESIGN: We included RCTs that primarily recruited adults with CDAD and compared the effectiveness of FMT with that of placebo, antibiotic therapy, or autologous stool transplantation, or compared different preparations or modes of delivery of FMT. Dichotomous symptom data were pooled to calculate a relative risk (RR) of CDAD persisting after therapy, and the number needed to treat (NNT).<br><br>DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched to 6 February 2017.<br><br>DATA SYNTHESIS: We identified ten RCTs that evaluated the treatment of a total of 657 patients with CDAD. Five RCTs compared FMT with placebo (including autologous FMT) or vancomycin treatment (total of 284 patients); FMT was statistically significantly more effective (RR, 0.41; 95% CI, 0.22-0.74; NNT, 3; 95% CI, 2-7). Heterogeneity across studies was significant (I[2] = 61%); this heterogeneity was attributable to the mode of delivery of FMT, and to the therapy being more successful in European than in North American trials. The other five RCTs evaluated different approaches to FMT therapy. Frozen FMT preparations were as efficacious as fresh material in one RCT, but the numbers of patients in the remaining RCTs were too small to allow definitive conclusions.<br><br>CONCLUSIONS: Moderate quality evidence from RCT trials indicates that FMT is more effective in patients with CDAD than vancomycin or placebo. Further investigations are needed to determine the best route of administration and FMT preparation.}, }
@article {pmid28812413, year = {2018}, author = {Gerth-Kahlert, C and Tiwari, A and Hauri-Hohl, MM and Hanson, JVM and Bahr, A and Palmowski-Wolfe, A and Güngör, T and Berger, W}, title = {Unusual retinopathy in a child with severe combined immune deficiency.}, journal = {Ophthalmic genetics}, volume = {39}, number = {1}, pages = {92-94}, doi = {10.1080/13816810.2017.1350721}, pmid = {28812413}, issn = {1744-5094}, mesh = {DNA, Viral/genetics ; Enterovirus/genetics/isolation &amp; purification ; Enterovirus Infections/*diagnosis/virology ; Eye Infections, Viral/*diagnosis/virology ; Feces/virology ; Female ; Follow-Up Studies ; Humans ; Infant ; Polymerase Chain Reaction ; Retinal Diseases/*diagnosis/virology ; Severe Combined Immunodeficiency/*diagnosis/therapy/virology ; Stem Cell Transplantation ; Vision, Low/diagnosis ; Exome Sequencing ; }, abstract = {We describe a case of an infant diagnosed with severe combined immune deficiency (Adenosine Deaminase (ADA), SCID) with severe retinopathy and associated low vision in both eyes at first examination. An extensive infectious work up revealed an enterovirus infection, which suggested an early infectious and severe retinopathy. Genetic causes of congenital retinitis pigmentosa/ Leber's congenital amaurosis could be excluded by whole exome sequencing.}, }
@article {pmid28811841, year = {2017}, author = {Łusiak-Szelachowska, M and Weber-Dąbrowska, B and Jończyk-Matysiak, E and Wojciechowska, R and Górski, A}, title = {Bacteriophages in the gastrointestinal tract and their implications.}, journal = {Gut pathogens}, volume = {9}, number = {}, pages = {44}, pmid = {28811841}, issn = {1757-4749}, abstract = {The gut microbiota plays an essential role in health and disease of humans. Bacteriophages are the most abundant members of the gut virobiota and display great diversity. Phages can translocate through the mucosa to lymph and internal organs and play a role as regulators of the bacterial population in the gut. Increasing abundance of phages in the gut mucosa may reduce colonization by bacteria. Moreover, phages may have an immunomodulatory role in the immune response in the human gut. The role of phages in inflammatory bowel disease (IBD) remains unknown. Phages may take part in the development of IBD, but there are also data suggesting the protective role of phages in the gut of patients with IBD. Furthermore, recent data suggest that phages may mediate the beneficial effects of fecal microbiota transplantation (FMT). Therefore, evidence is accumulating to highlight the protective immunomodulating activity of the gut phages.}, }
@article {pmid28811492, year = {2017}, author = {van de Garde, MDB and Pas, SD and van Oord, GW and Gama, L and Choi, Y and de Man, RA and Boonstra, A and Vanwolleghem, T}, title = {Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {8267}, pmid = {28811492}, issn = {2045-2322}, support = {P30 AI094189/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antiviral Agents/*pharmacology ; Biomarkers ; Chemokine CXCL10/blood/metabolism ; Disease Models, Animal ; Hepatitis B virus/drug effects ; Hepatitis E/drug therapy/immunology/metabolism/*virology ; Hepatitis E virus/*drug effects/immunology ; Heterografts ; Humans ; Immunity, Innate ; Interferon-alpha/*pharmacology ; Mice ; Polyethylene Glycols/pharmacology ; Recombinant Proteins/pharmacology ; Viral Load ; }, abstract = {Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals. Rapid viral clearance by pegIFNα was confirmed in HEV gt1, but not in Hepatitis B Virus infected animals. No ISG induction was observed in untreated HEV gt3 and gt1 infected humanized livers compared to control chimeric mice, irrespective of the human hepatocyte donor, viral isolate or HEV infection duration. Human specific ISG transcript levels in mouse liver increased significantly after pegIFNα treatment and induced high circulating human CXCL10 in mouse serum. In conclusion, HEV gt1 and gt3 infections do not elicit innate intrahepatic immune responses and remain highly sensitive to pegIFNα in immunocompromised humanized mice.}, }
@article {pmid28807067, year = {2017}, author = {Mahieu, R and Cassisa, V and Sanderink, D and Chenouard, R and Pailhoriès, H and Kempf, M and Dubée, V and Eveillard, M}, title = {Iterative Fecal Microbiota Transplantations for Eradicating Digestive Colonization With Carbapenemase-Producing Enterobacteriaceae: Is It Worth It?.}, journal = {Infection control and hospital epidemiology}, volume = {38}, number = {10}, pages = {1265-1266}, doi = {10.1017/ice.2017.173}, pmid = {28807067}, issn = {1559-6834}, mesh = {Animals ; Carbapenem-Resistant Enterobacteriaceae/isolation &amp; purification/*pathogenicity ; Colony Count, Microbial ; Disease Models, Animal ; Enterobacteriaceae Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Mice ; Random Allocation ; }, }
@article {pmid28805322, year = {2017}, author = {Lim, MH and Radford-Smith, GL}, title = {Editorial: faecal microbiota transplantation for ulcerative colitis-not quite there yet?.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {46}, number = {6}, pages = {630-631}, doi = {10.1111/apt.14228}, pmid = {28805322}, issn = {1365-2036}, mesh = {*Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Microbiota ; }, }
@article {pmid28805321, year = {2017}, author = {Costello, SP and Soo, W and Bryant, RV and Jairath, V and Hart, AL and Andrews, JM}, title = {Editorial: faecal microbiota transplantation for ulcerative colitis-not quite there yet? Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {46}, number = {6}, pages = {631-632}, doi = {10.1111/apt.14246}, pmid = {28805321}, issn = {1365-2036}, mesh = {*Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Microbiota ; }, }
@article {pmid28803667, year = {2018}, author = {Kang, Y and Cai, Y}, title = {Future prospect of faecal microbiota transplantation as a potential therapy in asthma.}, journal = {Allergologia et immunopathologia}, volume = {46}, number = {3}, pages = {307-309}, doi = {10.1016/j.aller.2017.04.008}, pmid = {28803667}, issn = {1578-1267}, mesh = {Asthma/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Humans ; Probiotics/therapeutic use ; }, abstract = {There is convincing evidence from both human and animal studies suggesting that the gut microbiota plays an important role in regulating immune responses associated with the development of asthma. Certain intestinal microbial strains have been demonstrated to suppress or impair immune responsiveness in asthma experimental models, suggesting that specific species among gut commensal microbiota may play either a morbific or phylactic role in the progression of asthma. Evidence to date suggests that the intestinal microbiota represent fertile targets for prevention or management of asthma. The faecal microbiota transplantation (FMT) is a rather straightforward therapy that manipulates the human gastrointestinal (GI) microbiota, by which a healthy donor microbiota is transferred into an existing but disturbed microbial ecosystem. The FMT may therefore represent a therapeutic approach for asthma treatment in the foreseeable future. At present, FMT therapy for asthma is very limited and should be actively studied. Considerable efforts are needed to increase our knowledge in the field of FMT therapy for asthma. In this review, we aimed to provide several insights into the development of FMT therapy for asthma.}, }
@article {pmid28801119, year = {2017}, author = {Jiang, ZD and Alexander, A and Ke, S and Valilis, EM and Hu, S and Li, B and DuPont, HL}, title = {Stability and efficacy of frozen and lyophilized fecal microbiota transplant (FMT) product in a mouse model of Clostridium difficile infection (CDI).}, journal = {Anaerobe}, volume = {48}, number = {}, pages = {110-114}, doi = {10.1016/j.anaerobe.2017.08.003}, pmid = {28801119}, issn = {1095-8274}, mesh = {Animals ; Clostridioides difficile/growth &amp; development/pathogenicity ; Clostridium Infections/microbiology/*therapy ; Cryopreservation/*methods ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Freezing ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Treatment Outcome ; }, abstract = {Freezing donor fecal microbiota has simplified fecal microbiota transplantation (FMT) in the treatment of recurrent C. difficile infection (CDI). However, the optimal storage time for the frozen FMT products remains unknown. Using an established murine model of CDI, stability and efficacy of frozen and lyophilized FMT product was studied at time points from 2 months to 15 months. DNA was extracted from fecal samples from the mice with identification of specific bacterial species by real-time quantitative PCR (qPCR). FMT product stability and efficacy were measured by occurrence of diarrhea in the challenged mice together with stability of the microbiota composition. The results were analyzed and compared by SAS statistical software. All mice treated with only C. difficile developed diarrhea within 72 h. Mice treated with frozen (n = 5/group), lyophilized (n = 5/group) products stored for ≤ 7-month or fresh FMT product (n = 22) were protected from post C. difficile challenge diarrhea. There was no difference between frozen and lyophilized products (n = 5/group) stored for ≤ 7 months 95% CI 1.00 (0.38-2.64) and 1.00 (0.38-2.64), respectively. Prevention if CDI by frozen and lyophilized product was not different for storage of 9-, 11- and 15-months. qPCR results demonstrated there were no significant quantitative change in Bacteroides and Clostridium species during any of the storage times (P > 0.05). In the present study, frozen and lyophilized FMT products were stored up to 7 months without losing microbiota composition and therapeutic efficacy. The animal model described may be useful to study stability of human microbiota designed for FMT.}, }
@article {pmid28799154, year = {2017}, author = {Reinshagen, M and Stallmach, A}, title = {[Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {55}, number = {8}, pages = {779-780}, doi = {10.1055/s-0043-109349}, pmid = {28799154}, issn = {1439-7803}, mesh = {*Colitis, Ulcerative ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid28796069, year = {2017}, author = {Zhu, J and Zhang, F and Zhou, J and Li, H}, title = {Assessment of therapeutic response in Crohn's disease using quantitative dynamic contrast enhanced MRI (DCE-MRI) parameters: A preliminary study.}, journal = {Medicine}, volume = {96}, number = {32}, pages = {e7759}, pmid = {28796069}, issn = {1536-5964}, mesh = {Adult ; C-Reactive Protein ; Contrast Media/*administration &amp; dosage ; Crohn Disease/*diagnostic imaging/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; ROC Curve ; Reproducibility of Results ; Sensitivity and Specificity ; Severity of Illness Index ; Young Adult ; }, abstract = {The aim of the study was to investigate dynamic contrast enhanced MRI (DCE-MRI) as a potential marker to assess the therapeutic responses of fecal microbiota transplantation (FMT) in patients with Crohn's disease (CD) and to determine the parameter or combination of parameters most strongly associated with changes in clinical indicators after treatment.In 22 CD patients, DCE-MRI was performed with a 3.0T scanner. Parameters of DCE-MRI (vascular transfer constant [K] and blood volume [BV]) in the terminal ileum were compared between before and day 90 after FMT treatment. The differences of clinical indicators (C-reactive protein [CRP], Harvey-Bradshaw index [HBI]) and DCE-MRI parameters (K, BV) between pre- and post-treatment was calculated by Student's 2-tailed, paired t-test. The correlations between percent change of clinical indicators (ΔCRP, ΔHBI) with DCE-MRI parameters (ΔK, ΔBV) were analyzed by Pearson's correlation coefficients. A logistic regression model was used to identify the changes of DCE-MRI parameters related to the treatment outcomes. Receiver operating characteristic curves (ROCs) were generated to assess which DCE-MRI parameter showed the best accuracy for evaluation of therapeutic response.After treatment, mean values of clinical indicators decreased significantly (CRP: 62.68 ± 31.86 vs 43.55 ± 29.63 mg/L, P = .008; HBI: 7.18 ± 2.10 vs 5.73 ± 2.33, P = 0.012). Both DCE-MRI parameters showed prominent differences before and after treatment: K (1.86 ± 0.87 vs 1.39 ± 0.83 min, P = .017), BV (61.02 ± 28.49 vs 41.96 ± 22.75 mL/100 g, P = .005). There were significant correlations between ΔCRP or ΔHBI and percent change of CDE-MRI parameters (ΔK to ΔCRP: 0.659; ΔK to ΔHBI: 0.496; ΔBV to ΔCRP: 0.442; ΔBV to ΔHBI: 0.476). Compared to ΔK and ΔBV individually, the combination of both parameters performed best in assessment of therapeutic response with an area under the ROCs (AUC) of 0.948.K and BV parameters derived from DCE-MRI have the potential to assess for therapeutic response after FMT treatment for CD. The combination of K and BV measurements improved the predictive capability compared to the individual parameters.}, }
@article {pmid28789710, year = {2017}, author = {Brooks, PT and Brakel, KA and Bell, JA and Bejcek, CE and Gilpin, T and Brudvig, JM and Mansfield, LS}, title = {Transplanted human fecal microbiota enhanced Guillain Barré syndrome autoantibody responses after Campylobacter jejuni infection in C57BL/6 mice.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {92}, pmid = {28789710}, issn = {2049-2618}, support = {N01AI30058/AI/NIAID NIH HHS/United States ; R21 AI121748/AI/NIAID NIH HHS/United States ; T35 RR017491/RR/NCRR NIH HHS/United States ; U19 AI090872/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Autoantibodies/*biosynthesis/blood/immunology ; Autoimmunity ; Campylobacter Infections/*immunology/microbiology ; Campylobacter jejuni/immunology ; Colitis/etiology/immunology/microbiology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Guillain-Barre Syndrome/*immunology/*microbiology ; Host-Pathogen Interactions ; Humans ; Inflammation ; Interleukin-10/immunology ; Interleukin-4/immunology ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Campylobacter jejuni is the leading antecedent infection to the autoimmune neuropathy Guillain-Barré syndrome (GBS), which is accompanied by an autoimmune anti-ganglioside antibody attack on peripheral nerves. Previously, we showed that contrasting immune responses mediate C. jejuni induced colitis and autoimmunity in interleukin-10 (IL-10)-deficient mice, dependent upon the infecting strain. Strains from colitis patients elicited T helper 1 (TH1)-dependent inflammatory responses while strains from GBS patients elicited TH2-dependent autoantibody production. Both syndromes were exacerbated by antibiotic depletion of the microbiota, but other factors controlling susceptibility to GBS are unknown.<br><br>METHODS: Using 16S rRNA gene high-throughput sequencing, we examined whether structure of the gut microbial community alters host (1) gastrointestinal inflammation or (2) anti-ganglioside antibody responses after infection with C. jejuni strains from colitis or GBS patients. We compared these responses in C57BL/6 mice with either (1) stable human gut microbiota ([Hu]microbiota) transplants or (2) conventional mouse microbiota ([Conv]microbiota).<br><br>RESULTS: Inoculating germ-free C57BL/6 wild-type (WT) mice with a mixed human fecal slurry provided a murine model that stably passed its microbiota over >20 generations. Mice were housed in specific pathogen-free (SPF) facilities, while extra precautions of having caretakers wear sterile garb along with limited access ensured that no mouse pathogens were acquired. [Hu]microbiota conferred many changes upon the WT model in contrast to previous results, which showed only colonization with no disease after C. jejuni challenge. When compared to [Conv]microbiota mice for susceptibility to C. jejuni enteric or GBS patient strains, infected [Hu]microbiota mice had (1) 10-100 fold increases in C. jejuni colonization of both strains, (2) pathologic change in draining lymph nodes but only mild changes in colon or cecal lamina propria, (3) significantly lower Th1/Th17-dependent anti-C. jejuni responses, (4) significantly higher IL-4 responses at 5 but not 7&#xa0;weeks post infection (PI), (5) significantly higher Th2-dependent anti-C. jejuni responses, and (6) significantly elevated anti-ganglioside autoantibodies after C. jejuni infection. These responses in [Hu]microbiota mice were correlated with a dominant Bacteroidetes and Firmicutes microbiota.<br><br>CONCLUSIONS: These data demonstrate that [Hu]microbiota altered host-pathogen interactions in infected mice, increasing colonization and Th-2 and autoimmune responses in a C. jejuni strain-dependent manner. Thus, microbiota composition is another factor controlling susceptibility to GBS.}, }
@article {pmid28787390, year = {2018}, author = {Flerlage, T and Hayden, R and Cross, SJ and Dallas, R and Srinivasan, A and Tang, L and Sun, Y and Maron, G}, title = {Rotavirus Infection in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients: Clinical Course and Experience Using Nitazoxanide and Enterally Administered Immunoglobulins.}, journal = {The Pediatric infectious disease journal}, volume = {37}, number = {2}, pages = {176-181}, doi = {10.1097/INF.0000000000001740}, pmid = {28787390}, issn = {1532-0987}, mesh = {Administration, Oral ; Adolescent ; Antiparasitic Agents/*therapeutic use ; Child ; Child, Preschool ; Cohort Studies ; Feces/virology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunization, Passive/methods ; Immunoglobulins/*administration &amp; dosage ; Infant ; Male ; Nitro Compounds ; Retrospective Studies ; Rotavirus ; Rotavirus Infections/*drug therapy/etiology ; Thiazoles/*therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Rotaviruses may produce prolonged and severe disease in allogeneic hematopoietic cell transplant (HCT) recipients. Nitazoxanide and enterally administered human immunoglobulins are potential therapeutic options. This retrospective study describes the clinical course of rotavirus infection in pediatric allogeneic HCT recipients and a single-center experience with nitazoxanide and oral immunoglobulins as potential treatment options.<br><br>METHODS: We identified 36 patients who had positive stool rotavirus antigen assays after allogeneic HCT from May 30, 2012, to July 31, 2015. Clinical, microbiologic and treatment data were collected and analyzed using descriptive statistics.<br><br>RESULTS: Forty-nine discrete episodes of rotavirus infection were identified among these 36 patients for a cumulative incidence of 19.7%. For these 49 episodes, the median day to infection after HCT was day 82, and the median duration of diarrhea was 17.5 days (range 4-122). Nitazoxanide and enteral immunoglobulins were prescribed for 41 episodes. The median duration of clinical symptoms after initiation of nitazoxanide was 11 days (range 2-85), 23 days (range 10-107) after enteral immunoglobulins and 26 days (range 6-90) after a combination of nitazoxanide and enteral immunoglobulins (P = 0.1). No adverse effects of either treatment were documented, but efficacy could not be assessed in this patient population.<br><br>CONCLUSIONS: In pediatric HCT recipients, the clinical illness produced by rotaviruses is prolonged compared with otherwise healthy children. Nitazoxanide appears safe, but its efficacy for this indication requires further study.}, }
@article {pmid28779831, year = {2017}, author = {Bartlett, JG}, title = {Clostridium difficile Infection.}, journal = {Infectious disease clinics of North America}, volume = {31}, number = {3}, pages = {489-495}, doi = {10.1016/j.idc.2017.05.012}, pmid = {28779831}, issn = {1557-9824}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Centers for Disease Control and Prevention, U.S. ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/microbiology/*prevention &amp; control/*therapy ; Cross Infection/diagnosis/microbiology/therapy ; Diarrhea/microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; Iatrogenic Disease ; Intensive Care Units ; Risk Factors ; United States/epidemiology ; }, abstract = {Clostridium difficile infection is a major health care challenge in terms of patient and economic consequences. For the patient, it is a morbid and sometimes a life-threatening iatrogenic complication of antibiotic treatment. In the United States, the provider's institution may face financial penalties, because the Centers for Disease Control and Prevention views this as an iatrogenic health care-associated complication that may not be reimbursable by the Centers for Medicare and Medicaid Services; this has resulted in substantial incentives for new approaches to prevention and treatment.}, }
@article {pmid28777432, year = {2017}, author = {Kriegshäuser, G and Enko, D and Zitt, M and Oberwalder, M and Oberkanins, C and Öfner, D and Zeillinger, R and Maximilian Müller, H}, title = {Comparison of a prototype reverse hybridization assay and MethyLight for detection of SFRP2 promotor methylation in fecal DNA.}, journal = {The International journal of biological markers}, volume = {32}, number = {4}, pages = {e467-e470}, doi = {10.5301/ijbm.5000289}, pmid = {28777432}, issn = {1724-6008}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Colorectal Neoplasms/diagnosis/*genetics/pathology ; DNA Methylation/genetics ; Early Detection of Cancer ; Feces ; Female ; Humans ; Male ; Membrane Proteins/*genetics ; Middle Aged ; Precancerous Conditions/diagnosis/*genetics/pathology ; Promoter Regions, Genetic ; }, abstract = {BACKGROUND: This study aimed to evaluate the diagnostic performance of a novel nonquantitative methylation-specific reverse hybridization (MSRH) assay to detect secreted frizzled-related protein 2 (SFRP2) promotor methylation in fecal DNA.<br><br>METHODS: SFRP2 promoter methylation was investigated in stool DNA isolated from 18 colorectal cancer (CRC) patients and 22 healthy controls using the MSRH assay based on methylation-specific DNA amplification followed by reverse hybridization of biotinylated amplicons to sequence-specific methylation detection probes, with MethyLight serving as a reference method.<br><br>RESULTS: SFRP2 promotor methylation as determined by MSRH vs. MethyLight showed a sensitivity and specificity of 61.1% and 86.3% vs. 77.7% and 77.3%, respectively. Moderate agreement (&#x138; = 0.54, 95% confidence interval [95% CI], 0.29-0.80, p<0.001) was observed between the 2 methods. However, the differences in SFRP2 promotor methylation observed between CRC patients and healthy individuals by both assays were statistically significant (p<0.001).<br><br>CONCLUSIONS: Our findings, although limited by the small sample size, do not support the use of the MSRH assay for CRC screening in stool.}, }
@article {pmid28770495, year = {2017}, author = {Millan, B and Laffin, M and Madsen, K}, title = {Fecal Microbiota Transplantation: Beyond Clostridium difficile.}, journal = {Current infectious disease reports}, volume = {19}, number = {9}, pages = {31}, pmid = {28770495}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: Fecal microbiota transplantation (FMT) has been established as standard of care in the treatment of antibiotic refractory Clostridium difficile infection (RCDI). This review examines the current evidence that exists to support the use of FMT in the treatment of human disease beyond C. difficile infection.<br><br>RECENT FINDINGS: Beneficial effects of FMT have been described in case series or small prospective trials on a wide spectrum of conditions, including inflammatory bowel disease, functional gastrointestinal disorders, non-alcoholic steatohepatitis, alcoholic hepatitis, hepatic encephalopathy, and neuropsychiatric conditions, and in limiting antibiotic-resistant bacterial infections. Each of these proposed indications for FMT is associated with an underlying dysbiosis of the gastrointestinal microbiota and generally a clinical response is linked with a restoration of the gut microbiota. The potential of fecal microbial transplantation to alter disease course shows promise but further large-scale studies are necessary to understand limitations as well as how best to utilize this therapy.}, }
@article {pmid28769880, year = {2017}, author = {Selber-Hnatiw, S and Rukundo, B and Ahmadi, M and Akoubi, H and Al-Bizri, H and Aliu, AF and Ambeaghen, TU and Avetisyan, L and Bahar, I and Baird, A and Begum, F and Ben Soussan, H and Blondeau-Éthier, V and Bordaries, R and Bramwell, H and Briggs, A and Bui, R and Carnevale, M and Chancharoen, M and Chevassus, T and Choi, JH and Coulombe, K and Couvrette, F and D'Abreau, S and Davies, M and Desbiens, MP and Di Maulo, T and Di Paolo, SA and Do Ponte, S and Dos Santos Ribeiro, P and Dubuc-Kanary, LA and Duncan, PK and Dupuis, F and El-Nounou, S and Eyangos, CN and Ferguson, NK and Flores-Chinchilla, NR and Fotakis, T and Gado Oumarou H D, M and Georgiev, M and Ghiassy, S and Glibetic, N and Grégoire Bouchard, J and Hassan, T and Huseen, I and Ibuna Quilatan, MF and Iozzo, T and Islam, S and Jaunky, DB and Jeyasegaram, A and Johnston, MA and Kahler, MR and Kaler, K and Kamani, C and Karimian Rad, H and Konidis, E and Konieczny, F and Kurianowicz, S and Lamothe, P and Legros, K and Leroux, S and Li, J and Lozano Rodriguez, ME and Luponio-Yoffe, S and Maalouf, Y and Mantha, J and McCormick, M and Mondragon, P and Narayana, T and Neretin, E and Nguyen, TTT and Niu, I and Nkemazem, RB and O'Donovan, M and Oueis, M and Paquette, S and Patel, N and Pecsi, E and Peters, J and Pettorelli, A and Poirier, C and Pompa, VR and Rajen, H and Ralph, RO and Rosales-Vasquez, J and Rubinshtein, D and Sakr, S and Sebai, MS and Serravalle, L and Sidibe, F and Sinnathurai, A and Soho, D and Sundarakrishnan, A and Svistkova, V and Ugbeye, TE and Vasconcelos, MS and Vincelli, M and Voitovich, O and Vrabel, P and Wang, L and Wasfi, M and Zha, CY and Gamberi, C}, title = {Human Gut Microbiota: Toward an Ecology of Disease.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1265}, pmid = {28769880}, issn = {1664-302X}, abstract = {Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics.}, }
@article {pmid28767077, year = {2017}, author = {Poeta, M and Pierri, L and Vajro, P}, title = {Gut-Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease.}, journal = {Children (Basel, Switzerland)}, volume = {4}, number = {8}, pages = {}, pmid = {28767077}, issn = {2227-9067}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A "multiple-hit" hypothesis has been invoked to explain its pathogenesis. The "first hit" is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as "second hits" implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut-liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising.}, }
@article {pmid28766951, year = {2017}, author = {Manthey, CF and Eckmann, L and Fuhrmann, V}, title = {Therapy for Clostridium difficile infection - any news beyond Metronidazole and Vancomycin?.}, journal = {Expert review of clinical pharmacology}, volume = {10}, number = {11}, pages = {1239-1250}, doi = {10.1080/17512433.2017.1362978}, pmid = {28766951}, issn = {1751-2441}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*drug therapy/microbiology ; Drug Design ; Humans ; Metronidazole/therapeutic use ; Practice Guidelines as Topic ; Recurrence ; Severity of Illness Index ; Vancomycin/therapeutic use ; }, abstract = {Infections with Clostridium difficile (CDI) represent a major burden for the health care system. Treatment is generally by antibiotic therapy with metronidazole and vancomycin, but efficacy remains suboptimal. Areas covered: This review discusses established and emerging treatment options for CDI, and current therapeutic guidelines, taking into account disease severity and risk of relapse. Expert commentary: New therapeutic approaches, including antibodies and new classes of antibiotics, and new measures for preventing infection with vaccines are under development in phase II/III clinical trials. We performed a systematic literature review using the search terms 'Clostridium difficile' and 'treatment'.}, }
@article {pmid28764868, year = {2017}, author = {Leber, A and Hontecillas, R and Abedi, V and Tubau-Juni, N and Zoccoli-Rodriguez, V and Stewart, C and Bassaganya-Riera, J}, title = {Modeling new immunoregulatory therapeutics as antimicrobial alternatives for treating Clostridium difficile infection.}, journal = {Artificial intelligence in medicine}, volume = {78}, number = {}, pages = {1-13}, doi = {10.1016/j.artmed.2017.05.003}, pmid = {28764868}, issn = {1873-2860}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Anti-Infective Agents ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Computer Simulation ; *Fecal Microbiota Transplantation ; Microbiota ; }, abstract = {The current treatment paradigm in Clostridium difficile infection is the administration of antibiotics contributing to the high rates of recurrent infections. Recent alternative strategies, such as fecal microbiome transplantation and anti-toxin antibodies, have shown similar efficacy in the treatment of C. difficile associated disease (CDAD). However, barriers exist for either treatment or other novel treatments to displace antibiotics as the standard of care. To aid in the comparison of these and future treatments in CDAD, we developed an in silico pipeline to predict clinical efficacy with nonclinical results. The pipeline combines an ordinary differential equation (ODE)-based model, describing the immunological and microbial interactions in the gastrointestinal (GI) mucosa, with machine learning algorithms to translate simulated output quantities (i.e. time of clearance, quantity of commensal bacteria, T cell ratios) into clinical predictions based on prior preclinical, translational and clinical trial data. As a use case, we compare the efficacy of lanthionine synthetase C-like 2 (LANCL2), a novel immunoregulatory target with promising efficacy in inflammatory bowel disease (IBD), activation with antibiotics, fecal microbiome transplantation and anti-toxin antibodies in the treatment of CDAD. We further validate the potential of LANCL2 pathway activation, in a mouse model of C. difficile infection in which it displays an ability to decrease weight loss and inflammatory cell types while protecting against mortality. The computational pipeline can serve as an important resource in the development of new treatment modalities.}, }
@article {pmid28761936, year = {2017}, author = {Jenior, ML and Leslie, JL and Young, VB and Schloss, PD}, title = {Clostridium difficile Colonizes Alternative Nutrient Niches during Infection across Distinct Murine Gut Microbiomes.}, journal = {mSystems}, volume = {2}, number = {4}, pages = {}, pmid = {28761936}, issn = {2379-5077}, support = {UL1 TR000433/TR/NCATS NIH HHS/United States ; T32 GM008353/GM/NIGMS NIH HHS/United States ; R01 GM099514/GM/NIGMS NIH HHS/United States ; T32 GM145304/GM/NIGMS NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; }, abstract = {Clostridium difficile is the largest single cause of hospital-acquired infection in the United States. A major risk factor for Clostridium difficile infection (CDI) is prior exposure to antibiotics, as they disrupt the gut bacterial community which protects from C. difficile colonization. Multiple antibiotic classes have been associated with CDI susceptibility, many leading to distinct community structures stemming from variation in bacterial targets of action. These community structures present separate metabolic challenges to C. difficile. Therefore, we hypothesized that the pathogen adapts its physiology to the nutrients within different gut environments. Utilizing an in vivo CDI model, we demonstrated that C. difficile highly colonized ceca of mice pretreated with any of three antibiotics from distinct classes. Levels of C. difficile spore formation and toxin activity varied between animals based on the antibiotic pretreatment. These physiologic processes in C. difficile are partially regulated by environmental nutrient concentrations. To investigate metabolic responses of the bacterium in vivo, we performed transcriptomic analysis of C. difficile from ceca of infected mice across pretreatments. This revealed heterogeneous expression in numerous catabolic pathways for diverse growth substrates. To assess which resources C. difficile exploited, we developed a genome-scale metabolic model with a transcriptome-enabled metabolite scoring algorithm integrating network architecture. This platform identified nutrients that C. difficile used preferentially between pretreatments, which were validated through untargeted mass spectrometry of each microbiome. Our results supported the hypothesis that C. difficile inhabits alternative nutrient niches across cecal microbiomes with increased preference for nitrogen-containing carbon sources, particularly Stickland fermentation substrates and host-derived glycans. IMPORTANCE Infection by the bacterium Clostridium difficile causes an inflammatory diarrheal disease which can become life threatening and has grown to be the most prevalent nosocomial infection. Susceptibility to C. difficile infection is strongly associated with previous antibiotic treatment, which disrupts the gut microbiota and reduces its ability to prevent colonization. In this study, we demonstrated that C. difficile altered pathogenesis between hosts pretreated with antibiotics from separate classes and exploited different nutrient sources across these environments. Our metabolite score calculation also provides a platform to study nutrient requirements of pathogens during an infection. Our results suggest that C. difficile colonization resistance is mediated by multiple groups of bacteria competing for several subsets of nutrients and could explain why total reintroduction of competitors through fecal microbial transplant currently is the most effective treatment for recurrent CDI. This work could ultimately contribute to the identification of targeted, context-dependent measures that prevent or reduce C. difficile colonization, including pre- and probiotic therapies.}, }
@article {pmid28761890, year = {2017}, author = {Fasullo, MJ and Al-Azzawi, Y and Abergel, J}, title = {Microscopic Colitis After Fecal Microbiota Transplant.}, journal = {ACG case reports journal}, volume = {4}, number = {}, pages = {e87}, pmid = {28761890}, issn = {2326-3253}, abstract = {Microscopic colitis (MC) is an inflammatory condition of the large bowel that is associated with chronic, nonbloody diarrhea. Colonoscopy usually demonstrates normal mucosa, while tissue biopsy reveals intraepithelial lymphocytes or a subepithelial collagen band. Although no specific antibody has been discovered, MC is associated with several autoimmune disorders such as celiac disease, Hashimoto's thyroiditis, and rheumatoid arthritis. There are only a small number of case reports documenting possible hereditary MC cases, but up to 12% of patients with MC have a family history of inflammatory bowel disease. Other associations include proton pump inhibitor use, cigarette smoking, HLA-DQ2/86, and possibly some gastrointestinal infections.}, }
@article {pmid28761687, year = {2017}, author = {Volkmann, ER and Hoffmann-Vold, AM and Chang, YL and Jacobs, JP and Tillisch, K and Mayer, EA and Clements, PJ and Hov, JR and Kummen, M and Midtvedt, &#xd8; and Lagishetty, V and Chang, L and Labus, JS and Molberg, &#xd8; and Braun, J}, title = {Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts.}, journal = {BMJ open gastroenterology}, volume = {4}, number = {1}, pages = {e000134}, pmid = {28761687}, issn = {2054-4774}, support = {T32 DK007180/DK/NIDDK NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; P30 DK041301/DK/NIDDK NIH HHS/United States ; P50 DK064539/DK/NIDDK NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; }, abstract = {OBJECTIVE: To compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms.<br><br>DESIGN: Adult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in this study (1:1:1). All participants provided stool specimens for 16S rRNA sequencing. Linear discriminant analysis effect size demonstrated genera with differential expression in SSc. Differential expression analysis for sequence count data identified specific genera associated with GIT symptoms as assessed by the GIT 2.0 questionnaire.<br><br>RESULTS: The UCLA-SSc and OUH-SSc cohorts were similar in age (52.1 and 60.5&#x2005;years, respectively), disease duration (median (IQR): 6.6 (2.5-16.4) and 7.0 (1.0-19.2) years, respectively), gender distribution (88% and 71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6) and 0.6 (0.5), respectively). Principal coordinate analysis illustrated significant microbial community differences between SSc and controls (UCLA: p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of commensal genera deemed to protect against inflammation, such as Bacteroides (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls. Increased abundance of Clostridium was associated with less severe GIT symptoms in both cohorts.<br><br>CONCLUSIONS: The present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from 2 geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state.}, }
@article {pmid28760488, year = {2017}, author = {Ma, B and Pan, Q and Peppelenbosch, MP}, title = {Genetically Engineered Bacteria for Treating Human Disease.}, journal = {Trends in pharmacological sciences}, volume = {38}, number = {9}, pages = {763-764}, doi = {10.1016/j.tips.2017.07.001}, pmid = {28760488}, issn = {1873-3735}, mesh = {Bacteria/*genetics ; Bacterial Infections/*microbiology/*therapy ; Bacterial Physiological Phenomena ; Fecal Microbiota Transplantation ; Genetic Engineering ; Humans ; }, abstract = {Bacteria have now been harnessed to combat human diseases, especially to meet the challenge of antimicrobial resistance. Modulating the microbiome, particularly by genetically engineering the bacteria, has provided proof-of-concept as potential pharmacotherapy, but those involved in this field should engage in discussion as how to move forward.}, }
@article {pmid28760163, year = {2017}, author = {Staley, C and Kaiser, T and Beura, LK and Hamilton, MJ and Weingarden, AR and Bobr, A and Kang, J and Masopust, D and Sadowsky, MJ and Khoruts, A}, title = {Stable engraftment of human microbiota into mice with a single oral gavage following antibiotic conditioning.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {87}, pmid = {28760163}, issn = {2049-2618}, support = {R01 AI084913/AI/NIAID NIH HHS/United States ; R21 AI114722/AI/NIAID NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacteria/isolation &amp; purification ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Mice ; *Microbiota ; *Models, Animal ; }, abstract = {BACKGROUND: Human microbiota-associated (HMA) animal models relying on germ-free recipient mice are being used to study the relationship between intestinal microbiota and human disease. However, transfer of microbiota into germ-free animals also triggers global developmental changes in the recipient intestine, which can mask disease-specific attributes of the donor material. Therefore, a simple model of replacing microbiota into a developmentally mature intestinal environment remains highly desirable.<br><br>RESULTS: Here we report on the development of a sequential, three-course antibiotic conditioning regimen that allows sustained engraftment of intestinal microorganisms following a single oral gavage with human donor microbiota. SourceTracker, a Bayesian, OTU-based algorithm, indicated that 59.3&#xa0;&#xb1;&#xa0;3.0% of the fecal bacterial communities in treated mice were attributable to the donor source. This overall degree of microbiota engraftment was similar in mice conditioned with antibiotics and germ-free mice. Limited surveys of systemic and mucosal immune sites did not show evidence of immune activation following introduction of human microbiota.<br><br>CONCLUSIONS: The antibiotic treatment protocol described here followed by a single gavage of human microbiota may provide a useful, complimentary HMA model to that established in germ-free facilities. The model has the potential for further in-depth translational investigations of microbiota in a variety of human disease states.}, }
@article {pmid28759053, year = {2017}, author = {Legoff, J and Resche-Rigon, M and Bouquet, J and Robin, M and Naccache, SN and Mercier-Delarue, S and Federman, S and Samayoa, E and Rousseau, C and Piron, P and Kapel, N and Simon, F and Socié, G and Chiu, CY}, title = {The eukaryotic gut virome in hematopoietic stem cell transplantation: new clues in enteric graft-versus-host disease.}, journal = {Nature medicine}, volume = {23}, number = {9}, pages = {1080-1085}, pmid = {28759053}, issn = {1546-170X}, mesh = {Adolescent ; Adult ; Aged ; Anelloviridae/genetics/immunology ; DNA, Viral/*analysis ; Feces/chemistry ; Female ; Gastrointestinal Microbiome/genetics/*immunology ; Graft vs Host Disease/*immunology ; *Hematopoietic Stem Cell Transplantation ; Herpesviridae/genetics/immunology ; Humans ; Intestinal Diseases/*immunology ; Intestines/*virology ; Leukocyte L1 Antigen Complex/metabolism ; Male ; Metagenomics ; Middle Aged ; Papillomaviridae/genetics/immunology ; Picobirnavirus/genetics/immunology ; Polyomaviridae/genetics/immunology ; Proportional Hazards Models ; Risk Factors ; Severity of Illness Index ; Transplantation, Homologous ; Young Adult ; alpha 1-Antitrypsin/metabolism ; }, abstract = {Much attention has been focused on the role of the bacterial microbiome in human health, but the virome is understudied. Although previously investigated in individuals with inflammatory bowel diseases or solid-organ transplants, virome dynamics in allogeneic hematopoietic stem cell transplantation (HSCT) and enteric graft-versus-host disease (GVHD) remain unexplored. Here we characterize the longitudinal gut virome in 44 recipients of HSCT using metagenomics. A viral 'bloom' was identified, and significant increases were demonstrated in the overall proportion of vertebrate viral sequences following transplantation (P = 0.02). Increases in both the rates of detection (P < 0.0001) and number of sequences (P = 0.047) of persistent DNA viruses (anelloviruses, herpesviruses, papillomaviruses and polyomaviruses) over time were observed in individuals with enteric GVHD relative to those without, a finding accompanied by a reduced phage richness (P = 0.01). Picobirnaviruses were detected in 18 individuals (40.9%), more frequently before or within a week after transplant than at later time points (P = 0.008). In a time-dependent Cox proportional-hazards model, picobirnaviruses were predictive of the occurrence of severe enteric GVHD (hazard ratio, 2.66; 95% confidence interval (CI) = 1.46-4.86; P = 0.001), and correlated with higher fecal levels of two GVHD severity markers, calprotectin and α1-antitrypsin. These results reveal a progressive expansion of vertebrate viral infections over time following HSCT, and they suggest an unexpected association of picobirnaviruses with early post-transplant GVHD.}, }
@article {pmid28756077, year = {2017}, author = {Chong-Nguyen, C and Duboc, H and Sokol, H}, title = {[The gut microbiota, a new cardiovascular risk factor?].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {46}, number = {7-8 Pt 1}, pages = {708-713}, doi = {10.1016/j.lpm.2017.06.005}, pmid = {28756077}, issn = {2213-0276}, mesh = {Anti-Bacterial Agents/therapeutic use ; Cardiovascular Diseases/*physiopathology ; Dysbiosis/*physiopathology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Prebiotics ; Probiotics/therapeutic use ; Risk Factors ; }, abstract = {The gut microbiota is considered as our other "brain" and is implicated in several regulation of physiological metabolisms. The circulating level of TMAO, a metabolite of the gut microbiota, is directly correlated to the occurrence of cardiovascular events. Bile acids are protective metabolites against cardiovascular diseases through their anti-inflammatory and anti-atherogenic effects. The disturbance in the metabolism and the composition of the gut microbiota is called "dysbiosis". Understanding the implication of the gut microbiota and developing new therapeutic strategies are promising research fields to manage metabolic and cardiovascular diseases.}, }
@article {pmid28748314, year = {2017}, author = {Cheng, YW and Fischer, M}, title = {The Present Status of Fecal Microbiota Transplantation and Its Value in the Elderly.}, journal = {Current treatment options in gastroenterology}, volume = {15}, number = {3}, pages = {349-362}, pmid = {28748314}, issn = {1092-8472}, abstract = {OPINION STATEMENT: PURPOSE OF REVIEW: This article will review current literature describing fecal microbiota transplantation (FMT) in the treatment of various diseases, and its potential role in elderly patients (age ≥ 65 years).<br><br>RECENT FINDINGS: Research on FMT has blossomed in the last decade and its pivotal role in the treatment of recurrent Clostridium difficile infection (CDI) has been recognized by the American College of Gastroenterology in the latest guidelines. There is also emerging evidence that FMT may be beneficial in the treatment of severe and/or complicated CDI refractory to medical therapy, resulting in decreased rates of colectomy and mortality. In the elderly, CDI is associated with markedly higher rates of mortality and colectomy; outcomes are even worse when patients have underlying inflammatory bowel disease (IBD). While the majority of patients who receive FMT for CDI are older, only a handful of studies focused specifically on FMT treatment outcomes and safety in this age group. Current data corroborate the efficacy and safety profile of FMT, while also supporting its use for recurrent, severe, and/or complicated CDI in the elderly population. FMT is recommended for the treatment of recurrent, severe, and/or complicated CDI in patients older than 65&#xa0;years of age. It may be prudent to offer FMT earlier in the disease course, possibly after just the second recurrence and for the first episode of severe CDI to avert complications including colectomy and end-organ failure that elderly patients are more prone to developing.}, }
@article {pmid28747917, year = {2017}, author = {Li, M and Wang, B and Sun, X and Tang, Y and Wei, X and Ge, B and Tang, Y and Deng, Y and He, C and Yuan, J and Li, X}, title = {Upregulation of Intestinal Barrier Function in Mice with DSS-Induced Colitis by a Defined Bacterial Consortium Is Associated with Expansion of IL-17A Producing Gamma Delta T Cells.}, journal = {Frontiers in immunology}, volume = {8}, number = {}, pages = {824}, pmid = {28747917}, issn = {1664-3224}, abstract = {Bacterial consortium transplantation (BCT) is a promising alternative to fecal microbiota transplantation in treating inflammatory bowel disease (IBD). Here, we showed that a defined bacterial consortium derived from healthy mice was able to enhance the intestinal barrier function of mice with dextran sulfate sodium (DSS)-induced colitis. Interestingly, we found that the bacterial consortium significantly promoted the expansion of IL-17A-producing γδT (γδT17) cells in colonic lamina propria, which was closely associated with changing of intestinal microbial composition. The increased IL-17A secretion upon treatment with microbial products derived from the bacterial consortium was accompanied with upregulation of TLR2 expression by γδT cells, and it might be responsible for the upregulation of mucosal barrier function through IL-17R-ACT1-mediated recovery of the disrupted occludin subcellular location. Changing of some specific microbial groups such as Bifidobacterium and Bacillus spp. was closely correlated with the promotion of TLR2[+] γδT cells. Our results support that BCT can restore the alliance between commensal microbiota and intestinal γδT cells, which contributes to the improvement of intestinal barrier function. This study provides new insight into the development of bacteria transplantation therapy for the treatment of IBD.}, }
@article {pmid28747056, year = {2017}, author = {Izquierdo Romero, M and Varela Trastoy, P and Mancebo Mata, A}, title = {Fecal transplantation as a treatment for Clostridium difficile infection in patients with ulcerative colitis.}, journal = {Revista espanola de enfermedades digestivas}, volume = {109}, number = {9}, pages = {670}, doi = {10.17235/reed.2017.4941/2017}, pmid = {28747056}, issn = {1130-0108}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; *Clostridioides difficile ; Colitis, Ulcerative/complications/diagnostic imaging/*drug therapy ; Enterocolitis, Pseudomembranous/complications/drug therapy/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Agents/therapeutic use ; Humans ; Infliximab/therapeutic use ; Mesalamine/therapeutic use ; Middle Aged ; }, abstract = {Clostridium difficile (CD) infection is currently the most frequent etiology of nosocomial diarrhea. Besides, its incidence is progressively increasing in ambulatory patients. Inflammatory bowel disease (IBD) is a risk factor of CD infection itself, but also due to the regular immunosuppressive treatment used in these patients. At the present time, fecal transplantation (FT) is a safe and cost-effective alternative if the previous antibiotic treatments have failed. Similar outcomes between patients with IBD and general population have been reported. We present a case of a patient with ulcerative colitis and recurrent CD infection successfully treated with FT.}, }
@article {pmid28743891, year = {2017}, author = {Shankar, V and Agans, R and Paliy, O}, title = {Advantages of phylogenetic distance based constrained ordination analyses for the examination of microbial communities.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {6481}, pmid = {28743891}, issn = {2045-2322}, mesh = {Bacteroides/genetics ; Clostridioides difficile/pathogenicity ; Clostridium/genetics ; Clostridium Infections/microbiology/therapy ; Data Interpretation, Statistical ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Microbiota/genetics/*physiology ; *Phylogeny ; }, abstract = {Recently developed high throughput molecular techniques such as massively parallel sequencing and phylogenetic microarrays generate vast datasets providing insights into microbial community structure and function. Because of the high dimensionality of these datasets, multivariate ordination analyses are often employed to examine such data. Here, we show how the use of phylogenetic distance based redundancy analysis provides ecological interpretation of microbial community differences. We also extend the previously developed method of principal response curves to incorporate phylogenetic distance measure, and we demonstrate the improved ability of this approach to provide ecologically relevant insights into temporal alterations of microbial communities.}, }
@article {pmid28742949, year = {2017}, author = {Li, J and Riaz Rajoka, MS and Shao, D and Jiang, C and Jin, M and Huang, Q and Yang, H and Shi, J}, title = {Strategies to increase the efficacy of using gut microbiota for the modulation of obesity.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {18}, number = {11}, pages = {1260-1271}, doi = {10.1111/obr.12590}, pmid = {28742949}, issn = {1467-789X}, mesh = {Age Factors ; Anti-Bacterial Agents/therapeutic use ; Bariatric Surgery ; Diet ; Environmental Microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Life Style ; Obesity/*therapy ; Prebiotics ; Probiotics ; Sex Factors ; }, abstract = {Obesity is one of the most serious global public health challenges of the 21st century. The adjustment of gut microbiota is often recommended as an efficient strategy to treat obesity. This modulation of gut microbiota can be performed by many methods, including dietary intervention, antibiotic application, the use of prebiotics and probiotics, bariatric surgery and faecal microbiota transplantation. In most cases, positive effects have been observed in response to treatment, but invalid and even contrary effects have also been observed in some cases due to factors that are unrelated to intervention methods, such as genetic factors, patient age or gender, environmental microbiota, climate, geography and lifestyle. These factors can cause variation of gut microbial populations and thus should also be taken into consideration when selecting modulation strategies.}, }
@article {pmid28734127, year = {2017}, author = {Tandon, P and Madsen, K and Kao, D}, title = {Fecal microbiota transplantation for hepatic encephalopathy: Ready for prime time?.}, journal = {Hepatology (Baltimore, Md.)}, volume = {66}, number = {6}, pages = {1713-1715}, doi = {10.1002/hep.29396}, pmid = {28734127}, issn = {1527-3350}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous ; *Fecal Microbiota Transplantation ; Feces ; *Hepatic Encephalopathy ; Humans ; Microbiota ; }, }
@article {pmid28733895, year = {2017}, author = {Doki, N and Suyama, M and Sasajima, S and Ota, J and Igarashi, A and Mimura, I and Morita, H and Fujioka, Y and Sugiyama, D and Nishikawa, H and Shimazu, Y and Suda, W and Takeshita, K and Atarashi, K and Hattori, M and Sato, E and Watakabe-Inamoto, K and Yoshioka, K and Najima, Y and Kobayashi, T and Kakihana, K and Takahashi, N and Sakamaki, H and Honda, K and Ohashi, K}, title = {Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation.}, journal = {Annals of hematology}, volume = {96}, number = {9}, pages = {1517-1523}, doi = {10.1007/s00277-017-3069-8}, pmid = {28733895}, issn = {1432-0584}, mesh = {Acute Disease ; Adult ; Aged ; Allografts ; *Bacteroidetes/classification/genetics ; Disease-Free Survival ; Female ; *Firmicutes/classification/genetics ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/genetics/microbiology/mortality ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Survival Rate ; }, abstract = {Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (<2), intermediate (2, 3), and high (>3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p < 0.01) and a lower tendency for Bacteroidetes (p = 0.106) than non-aGVHD patients. Maintenance of Bacteroidetes throughout allo-HSCT may be a strategy to prevent aGVHD.}, }
@article {pmid28728967, year = {2017}, author = {Galloway-Peña, J and Brumlow, C and Shelburne, S}, title = {Impact of the Microbiota on Bacterial Infections during Cancer Treatment.}, journal = {Trends in microbiology}, volume = {25}, number = {12}, pages = {992-1004}, doi = {10.1016/j.tim.2017.06.006}, pmid = {28728967}, issn = {1878-4380}, mesh = {Bacterial Infections/*complications ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Humans ; Microbiota/*immunology ; Neoplasms/*complications/*drug therapy ; }, abstract = {Patients being treated for cancer are at high risk for infectious complications, generally due to colonizing organisms that gain access to sterile sites via disrupted epithelial barriers. There is an emerging understanding that the ability of bacterial pathogens, including multidrug-resistant organisms, to colonize and subsequently infect humans is largely dependent on protective bacterial species present in the microbiome. Thus, herein we review recent studies demonstrating strong correlations between the microbiome of the oncology patient and infections occurring during chemotherapy. An increased knowledge of the interplay between potential pathogens, protective commensals, and the host immune system may facilitate the development of novel biomarkers or therapeutics that could help ameliorate the toll that infections take during the treatment of cancer.}, }
@article {pmid28728589, year = {2017}, author = {Paradies, P and Iarussi, F and Sasanelli, M and Capogna, A and Lia, RP and Zucca, D and Greco, B and Cantacessi, C and Otranto, D}, title = {Occurrence of strongyloidiasis in privately owned and sheltered dogs: clinical presentation and treatment outcome.}, journal = {Parasites &amp; vectors}, volume = {10}, number = {1}, pages = {345}, pmid = {28728589}, issn = {1756-3305}, mesh = {Animals ; Antinematodal Agents/therapeutic use ; Dog Diseases/*drug therapy/*epidemiology/parasitology/transmission ; Dogs ; Europe/epidemiology ; Feces/parasitology ; Fenbendazole/therapeutic use ; Humans ; Italy/epidemiology ; Male ; Pets/*parasitology ; Strongyloides stercoralis/isolation &amp; purification ; Strongyloidiasis/drug therapy/epidemiology/parasitology/*veterinary ; Treatment Outcome ; }, abstract = {BACKGROUND: The increasing number of reports of human infections by Strongyloides stercoralis from a range of European countries over the last 20 years has spurred the interest of the scientific community towards this parasite and, in particular, towards the role that infections of canine hosts may play in the epidemiology of human disease. Data on the epidemiology of canine strongyloidiasis is currently limited, most likely because of the inherent limitations of current diagnostic methods.<br><br>METHODS: Faecal samples were collected directly from the rectal ampulla of 272 animals of varying age and both genders living in Apulia, southern Italy. Dogs included were either privately owned (n&#xa0;=&#xa0;210), living in an urban area but with unrestricted outdoor access (Group 1), or shelter dogs (n&#xa0;=&#xa0;62 out of ~400) hosted in a single shelter in the province of Bari in which a history of diarrhoea, weight loss, reduced appetite and respiratory symptoms had been reported (Group 2). Strongyloides stercoralis infection was diagnosed by coproscopy on direct faecal smear and via the Baermann method.<br><br>RESULTS: Six of 272 dogs were positive for S. stercoralis at the Baermann examination; all but one were from the shelter (Group 2) and displayed gastrointestinal clinical signs. The only owned dog (Group 1) infected with S. stercoralis, but clinically healthy, had been adopted from a shelter 1&#xa0;year prior to sampling. Five infected dogs were treated with fenbendazole (Panacur&#xae;, Intervet, Animal Health, 50&#xa0;mg/kg, PO daily for 5&#xa0;days), or with a combination of fenbendazole and moxidectin plus imidacloprid spot-on (Im/Mox; Advocate&#xae; spot-on, Bayer). Post-treatment clearance of infection was confirmed in three dogs by Baermann examination, whereas treatment failure was documented in two dogs by Baermann and/or post-mortem detection of adult parasites.<br><br>CONCLUSIONS: This study describes, for the first time, the presence of S. stercoralis infection in sheltered dogs from southern Italy. Data indicate that S. stercoralis infection may pose a concern for sheltered animals and raise questions on potential risks of infection for staff of municipal shelters in southern European countries. Given that a single course of treatment with fenbendazole, associated or not with Im/Mox spot-on, may not eliminate the infection, effective treatment protocols should be investigated and control strategies targeting the environment considered for reducing the risk of zoonotic infection.}, }
@article {pmid28723262, year = {2017}, author = {Qazi, T and Amaratunga, T and Barnes, EL and Fischer, M and Kassam, Z and Allegretti, JR}, title = {The risk of inflammatory bowel disease flares after fecal microbiota transplantation: Systematic review and meta-analysis.}, journal = {Gut microbes}, volume = {8}, number = {6}, pages = {574-588}, pmid = {28723262}, issn = {1949-0984}, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*adverse effects ; Feces/microbiology ; Humans ; Inflammatory Bowel Diseases/*epidemiology/*etiology ; Risk ; Symptom Flare Up ; Treatment Outcome ; }, abstract = {UNLABELLED: Several studies have suggested worsening in inflammatory bowel disease (IBD) activity following fecal microbiota transplantation (FMT). We aimed to assess the risk of worsening in IBD activity following FMT. An electronic search was conducted using MEDLINE (1946-June 2016), EMBASE (1954-June 2016) and Cochrane Central Register of Controlled Trials (2016). Studies in which FMT was provided to IBD patients for IBD management or (Clostridium difficile infection) CDI treatment were included. The primary outcome was the rate of worsening in IBD activity.<br><br>RESULTS: Twenty-nine studies with 514 FMT-treated IBD patients were included. Range of follow up was 4 weeks to 3 y. The pooled rate of IBD worsening was 14.9% (95% CI 10-21%). Heterogeneity was detected: I2 D 52.1%, Cochran Q test D 58.1, p D 0.01. A priori subgroup analyses were performed. Although not significant, the pooled rate of worsening in IBD activity following FMT for CDI (22.7% (95% CI: 13-36%)) was higher compared with FMT for IBD (11.1% (95% CI 7-17%)). Rates of worsening in IBD after lower GI FMT delivery revealed a higher rate of worsening in IBD activity (16.5% (95% CI: 11-24%)) compared with upper GI delivery (5.6% (95% CI: 2-16%)). Rates of worsening in high quality studies and randomized controls trials (RCTS) suggested a marginal risk of worsening in IBD activity (4.6%, (95% CI: 1.8-11%). Rates of IBD worsening are overall marginal across high quality RCTS. It is unknown if the FMT itself led to the worsening of IBD in this small fraction or if this represents alternative etiologies.}, }
@article {pmid28721246, year = {2016}, author = {Udayappan, S and Manneras-Holm, L and Chaplin-Scott, A and Belzer, C and Herrema, H and Dallinga-Thie, GM and Duncan, SH and Stroes, ESG and Groen, AK and Flint, HJ and Backhed, F and de Vos, WM and Nieuwdorp, M}, title = {Oral treatment with Eubacterium hallii improves insulin sensitivity in db/db mice.}, journal = {NPJ biofilms and microbiomes}, volume = {2}, number = {}, pages = {16009}, pmid = {28721246}, issn = {2055-5008}, support = {250172/ERC_/European Research Council/International ; 615362/ERC_/European Research Council/International ; }, abstract = {An altered intestinal microbiota composition is associated with insulin resistance and type 2 diabetes mellitus. We previously identified increased intestinal levels of Eubacterium hallii, an anaerobic bacterium belonging to the butyrate-producing Lachnospiraceae family, in metabolic syndrome subjects who received a faecal transplant from a lean donor. To further assess the effects of E. hallii on insulin sensitivity, we orally treated obese and diabetic db/db mice with alive E. hallii and glycerol or heat-inactive E. hallii as control. Insulin tolerance tests and hyperinsulinemic-euglycemic clamp experiments revealed that alive E. hallii treatment improved insulin sensitivity compared control treatment. In addition, E. hallii treatment increased energy expenditure in db/db mice. Active E. hallii treatment was found to increase faecal butyrate concentrations and to modify bile acid metabolism compared with heat-inactivated controls. Our data suggest that E. hallii administration potentially alters the function of the intestinal microbiome and that microbial metabolites may contribute to the improved metabolic phenotype.}, }
@article {pmid28721078, year = {2017}, author = {Chong, Y and Shimoda, S and Miyake, N and Aoki, T and Ito, Y and Kamimura, T and Shimono, N}, title = {Incomplete recovery of the fecal flora of hematological patients with neutropenia and repeated fluoroquinolone prophylaxis.}, journal = {Infection and drug resistance}, volume = {10}, number = {}, pages = {193-199}, pmid = {28721078}, issn = {1178-6973}, abstract = {BACKGROUND: Routine fluoroquinolone prophylaxis in neutropenic patients with hematological malignancies is still controversial, because of antibiotic resistance concerns. The recovery of the fecal microbiota to the initial composition in patients receiving multiple courses of quinolone prophylaxis and repeated chemotherapy has not been evaluated.<br><br>METHODS: We prospectively examined the changes in the fecal bacterial composition before and after levofloxacin prophylaxis. A sequential observation of bacterial resistance in patients receiving multiple prophylactic courses was also conducted.<br><br>RESULTS: In this trial, 68 cases, including (35 with the first course and 33 with the second and subsequent courses) were registered. The disappearance of quinolone-susceptible (QS) Entero-bacteriaceae and dominant emergence of quinolone-resistant (QR) coagulase negative staphylococci (CNS) and QR Enterococci were observed after the first prophylaxis. The detection of QS Enterobacteriaceae was recovered before the second and subsequent courses to a level of the initial composition (28/35 samples, 80.0% before the first course vs 23/33 samples, 69.7% before the second and subsequent courses, P=0.41). In contrast, the detection rate of QR CNS and Enterococci significantly increased at the second and subsequent courses, even before prophylaxis (8/35 samples, 22.9% before the first course vs 20/33 samples, 60.6% before the second and subsequent courses, P=0.003). The incomplete recovery of the initial bacterial composition was associated with a prophylactic interval of within 30 days. Of the patients receiving multiple prophylactic courses, six had QR Escherichia coli, including extended-spectrum &#x3b2;-lactamase (ESBL) producers, at the first course, and four (66.3%) of the six patients had persistent detection of QR E. coli at the second course.<br><br>CONCLUSION: In patients receiving multiple courses of prophylactic quinolone, along with a common chemotherapy schedule, newly emergent resistant bacteria could be frequently persistent in their fecal flora.}, }
@article {pmid28719392, year = {2017}, author = {Volkmann, ER}, title = {Intestinal microbiome in scleroderma: recent progress.}, journal = {Current opinion in rheumatology}, volume = {29}, number = {6}, pages = {553-560}, doi = {10.1097/BOR.0000000000000429}, pmid = {28719392}, issn = {1531-6963}, mesh = {Gastrointestinal Microbiome/*immunology ; Homeostasis/immunology ; Humans ; Inflammation/immunology/microbiology ; Scleroderma, Systemic/*microbiology ; Symbiosis/immunology ; }, abstract = {PURPOSE OF REVIEW: Our evolving understanding of how gut microbiota affects immune function and homeostasis has led many investigators to explore the potentially pathologic role of gut microbiota in autoimmune diseases. This review will discuss the rapidly advancing field of microbiome research in systemic sclerosis (SSc), an incurable autoimmune disease with significant gastrointestinal morbidity and mortality.<br><br>RECENT FINDINGS: Recent reports have identified common perturbations in gut microbiota across different SSc cohorts. Compared with healthy controls, patients with SSc have decreased abundance of beneficial commensal genera (e.g. Faecalibacterium, Clostridium and Bacteroides) and increased abundance of pathbiont genera (e.g. Fusobacterium, Prevotella and Erwinia). Certain genera may protect against (e.g. Bacteroides, Clostridium, and Lactobacillus), or conversely exacerbate (e.g. Fusobacterium and Prevotella) gastrointestinal symptoms in SSc. These genera represent potential targets to avert or treat gastrointestinal dysfunction in SSc.<br><br>SUMMARY: Emerging evidence suggests that alterations in gut microbiota exist in the SSc disease state; however, future basic and clinical studies are needed to ascertain the mechanism by which these alterations perpetuate inflammation and fibrosis in SSc. Therapeutic trials are also needed to investigate whether dietary interventions or fecal transplantation can restore the gut microbial balance and improve health outcomes in SSc. VIDEO ABSTRACT: http://links.lww.com/COR/A38.}, }
@article {pmid28714946, year = {2017}, author = {Innes, AJ and Mullish, BH and Fernando, F and Adams, G and Marchesi, JR and Apperley, JF and Brannigan, E and Davies, F and Pavlů, J}, title = {Faecal microbiota transplant: a novel biological approach to extensively drug-resistant organism-related non-relapse mortality.}, journal = {Bone marrow transplantation}, volume = {52}, number = {10}, pages = {1452-1454}, pmid = {28714946}, issn = {1476-5365}, mesh = {Allografts ; Antineoplastic Combined Chemotherapy Protocols/*administration &amp; dosage ; Asparaginase/administration &amp; dosage ; *Bacteria/growth &amp; development/isolation &amp; purification ; Daunorubicin/administration &amp; dosage ; *Drug Resistance, Bacterial ; Fatal Outcome ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Methotrexate/administration &amp; dosage ; Middle Aged ; *Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*therapy ; Prednisolone/administration &amp; dosage ; Vincristine/administration &amp; dosage ; }, }
@article {pmid28714344, year = {2018}, author = {Barfield, E and Small, L and Navallo, L and Solomon, A}, title = {Going to the Bank: Fecal Microbiota Transplantation in Pediatrics.}, journal = {Clinical pediatrics}, volume = {57}, number = {4}, pages = {481-483}, doi = {10.1177/0009922817721159}, pmid = {28714344}, issn = {1938-2707}, mesh = {Adolescent ; Adult ; *Biological Specimen Banks ; Child ; Child, Preschool ; Clostridioides difficile ; Colonoscopy/methods ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Infant ; Male ; New York City ; Pediatrics/methods ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, }
@article {pmid28714089, year = {2017}, author = {Mullish, BH and McDonald, JAK and Thursz, MR and Marchesi, JR}, title = {Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial.}, journal = {Hepatology (Baltimore, Md.)}, volume = {66}, number = {4}, pages = {1354-1355}, doi = {10.1002/hep.29369}, pmid = {28714089}, issn = {1527-3350}, mesh = {*Fecal Microbiota Transplantation ; Feces ; *Hepatic Encephalopathy ; Humans ; Microbiota ; }, }
@article {pmid28714029, year = {2017}, author = {Yang, M and Fukui, H and Eda, H and Kitayama, Y and Hara, K and Kodani, M and Tomita, T and Oshima, T and Watari, J and Miwa, H}, title = {Involvement of gut microbiota in the association between gastrointestinal motility and 5‑HT expression/M2 macrophage abundance in the gastrointestinal tract.}, journal = {Molecular medicine reports}, volume = {16}, number = {3}, pages = {3482-3488}, doi = {10.3892/mmr.2017.6955}, pmid = {28714029}, issn = {1791-3004}, mesh = {Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Gastrointestinal Motility ; Gastrointestinal Tract/cytology/*microbiology/*physiology ; Germ-Free Life ; Intestinal Mucosa/metabolism ; Lectins, C-Type/metabolism ; Macrophages/*metabolism ; Male ; Mannose Receptor ; Mannose-Binding Lectins/metabolism ; Mice, Inbred ICR ; Organ Specificity ; Receptors, Cell Surface/metabolism ; Serotonin/*metabolism ; Time Factors ; }, abstract = {Serotonin (5‑hydroxytryptamine; 5‑HT) may be a key player in gastrointestinal (GI) motility and the GI immune system. In the present study, the effect of gut microbiota on the association between GI motility, and 5‑HT expression and macrophage abundance in the GI tract was examined. Germ‑free (GF) mice (6 weeks old) were orally administered a fecal bacterial suspension prepared from specific pathogen‑free mice and their GI tissues were evaluated 4 weeks later. The expression of 5‑HT and mannose receptor (MR) was examined by immunohistochemistry, and GI transit time (GITT) was measured by administration of carmine red solution. The numbers of 5‑HT‑positive endocrine cells and muscularis MR‑positive macrophages were significantly increased in the upper GI and colon of GF mice subjected to fecal transplantation (FT) compared with control GF mice without FT. GITT was significantly decreased in GF mice subjected to FT compared with GF mice without FT, and negatively correlated with the numbers of 5‑HT‑positive cells in the upper GI and muscularis MR‑positive macrophages throughout the GI tract. The numbers of 5‑HT‑positive endocrine cells and muscularis MR‑positive macrophages were significantly correlated throughout the GI tract. The present results suggest that the gut microbiota is involved in the association between accelerated GI motility and induction of the 5‑HT/muscularis MR‑positive macrophage axis in the GI tract.}, }
@article {pmid28711782, year = {2017}, author = {Blum, HE}, title = {The human microbiome.}, journal = {Advances in medical sciences}, volume = {62}, number = {2}, pages = {414-420}, doi = {10.1016/j.advms.2017.04.005}, pmid = {28711782}, issn = {1898-4002}, mesh = {Bacteria ; *Bacterial Physiological Phenomena ; Biodiversity ; *Disease ; Humans ; *Microbiota ; }, abstract = {Until recently, human microbiology was based on the identification of single microbes, such as bacteria, fungi and viruses, frequently isolated from patients with acute or chronic infections. Novel culture-independent molecular biochemical analyses (genomics, transcriptomics, proteomics, metabolomics) allow today to detect and classify the diverse microorganisms in a given ecosystem (microbiota), such as the gastrointestinal tract, the skin, the airway system, the urogenital tract and others, and to assess all genomes in these ecosystems (microbiome) as well as their gene products. These analyses revealed that each individual has its own microbiota that plays a role in health and disease. In addition, they greatly contributed to the recent advances in the understanding of the pathogenesis of a wide range of human diseases. It is to be expected that these new insights will translate into diagnostic, therapeutic and preventive measures in the context of personalized/precision medicine.}, }
@article {pmid28708089, year = {2017}, author = {Uebanso, T and Kano, S and Yoshimoto, A and Naito, C and Shimohata, T and Mawatari, K and Takahashi, A}, title = {Effects of Consuming Xylitol on Gut Microbiota and Lipid Metabolism in Mice.}, journal = {Nutrients}, volume = {9}, number = {7}, pages = {}, pmid = {28708089}, issn = {2072-6643}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Bacteria/classification/genetics ; DNA, Bacterial/analysis ; *Diet ; Diet, High-Fat ; Drinking ; Dyslipidemias/drug therapy/etiology ; Electrophoresis/methods ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Glucose Tolerance Test ; Lipid Metabolism/*drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Sequence Analysis, DNA ; *Sweetening Agents ; Xylitol/administration &amp; dosage/*pharmacology/therapeutic use ; }, abstract = {The sugar alcohol xylitol inhibits the growth of some bacterial species including Streptococcus mutans. It is used as a food additive to prevent caries. We previously showed that 1.5-4.0 g/kg body weight/day xylitol as part of a high-fat diet (HFD) improved lipid metabolism in rats. However, the effects of lower daily doses of dietary xylitol on gut microbiota and lipid metabolism are unclear. We examined the effect of 40 and 200 mg/kg body weight/day xylitol intake on gut microbiota and lipid metabolism in mice. Bacterial compositions were characterized by denaturing gradient gel electrophoresis and targeted real-time PCR. Luminal metabolites were determined by capillary electrophoresis electrospray ionization time-of-flight mass spectrometry. Plasma lipid parameters and glucose tolerance were examined. Dietary supplementation with low- or medium-dose xylitol (40 or 194 mg/kg body weight/day, respectively) significantly altered the fecal microbiota composition in mice. Relative to mice not fed xylitol, the addition of medium-dose xylitol to a regular and HFD in experimental mice reduced the abundance of fecal Bacteroidetes phylum and the genus Barnesiella, whereas the abundance of Firmicutes phylum and the genus Prevotella was increased in mice fed an HFD with medium-dose dietary xylitol. Body composition, hepatic and serum lipid parameters, oral glucose tolerance, and luminal metabolites were unaffected by xylitol consumption. In mice, 40 and 194 mg/kg body weight/day xylitol in the diet induced gradual changes in gut microbiota but not in lipid metabolism.}, }
@article {pmid28707337, year = {2017}, author = {Quraishi, MN and Widlak, M and Bhala, N and Moore, D and Price, M and Sharma, N and Iqbal, TH}, title = {Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {46}, number = {5}, pages = {479-493}, doi = {10.1111/apt.14201}, pmid = {28707337}, issn = {1365-2036}, support = {EME/13/179/01/DH_/Department of Health/United Kingdom ; }, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; Cross Infection ; Diarrhea/etiology ; Fecal Microbiota Transplantation/*methods ; Humans ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is the commonest nosocomial cause of diarrhoea. Faecal microbiota transplantation (FMT) is an approved treatment for recurrent or refractory CDI but there is uncertainty about its use.<br><br>AIM: To evaluate the efficacy of FMT in treating recurrent and refractory CDI and investigate outcomes from modes of delivery and preparation.<br><br>METHODS: A systematic review and meta-analysis was performed. MEDLINE, EMBASE, CINAHL, Cochrane Library, trial registers and conference proceedings were searched. Studies on FMT in recurrent and refractory CDI were included. The primary outcome was clinical resolution with subgroup analyses of modes of delivery and preparation. Random effects meta-analyses were used to combine data.<br><br>RESULTS: Thirty seven studies were included; seven randomised controlled trials and 30 case series. FMT was more effective than vancomycin (RR: 0.23 95%CI 0.07-0.80) in resolving recurrent and refractory CDI. Clinical resolution across all studies was 92% (95%CI 89%-94%). A significant difference was observed between lower GI and upper GI delivery of FMT 95% (95%CI 92%-97%) vs 88% (95%CI 82%-94%) respectively (P=.02). There was no difference between fresh and frozen FMT 92% (95%CI 89%-95%) vs 93% (95%CI 87%-97%) respectively (P=.84). Administering consecutive courses of FMT following failure of first FMT resulted in an incremental effect. Donor screening was consistent but variability existed in recipient preparation and volume of FMT. Serious adverse events were uncommon.<br><br>CONCLUSION: Faecal microbiota transplantation is an effective treatment for recurrent and refractory Clostridium difficile infection, independent of preparation and route of delivery.}, }
@article {pmid28702022, year = {2017}, author = {Ji, SK and Yan, H and Jiang, T and Guo, CY and Liu, JJ and Dong, SZ and Yang, KL and Wang, YJ and Cao, ZJ and Li, SL}, title = {Preparing the Gut with Antibiotics Enhances Gut Microbiota Reprogramming Efficiency by Promoting Xenomicrobiota Colonization.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1208}, pmid = {28702022}, issn = {1664-302X}, abstract = {Gut microbiota plays multiple important roles in intestinal and physiological homeostasis, and using fecal microbiota transplantation (FMT) to reprogram gut microbiota has demonstrated promise for redressing intestinal and physiological disorders. This study tested the alterations in reprogramming efficiency caused by different gut preparation procedures and explored the associated underlying mechanisms. We prepared the guts of mice for FMT by administering one of the three most-clinically used pretreatments [antibiotics, bowel cleansing (BC) solution, or no pretreatment], and we found that preparing the gut with antibiotics induced a more efficient modification of the gut bacterial community than was induced by either of the other two pretreatment types. The increased efficiency of antibiotic treatment appeared to occur via increasing the xenomicrobiota colonization. Further analysis demonstrated that antibiotic treatment of mice induced intestinal microbiota disruption, mostly by expelling antibiotic-sensitive bacteria, while the indigenous microbiota was maintained after treatment with a BC solution or in the absence of pretreatment. The amount of antibiotic-resistant bacteria increased shortly after antibiotics usage but subsequently decreased after FMT administration. Together, these results suggest that FMT relied on the available niches in the intestinal mucosa and that preparing the gut with antibiotics facilitated xenomicrobiota colonization in the intestinal mucosa, which thus enhanced the overall gut microbiota reprogramming efficiency.}, }
@article {pmid28695658, year = {2017}, author = {Laffin, M and Madsen, KL}, title = {Fecal Microbial Transplantation in Inflammatory Bowel Disease: A Movement Too Big to Be Ignored.}, journal = {Clinical pharmacology and therapeutics}, volume = {102}, number = {4}, pages = {588-590}, doi = {10.1002/cpt.747}, pmid = {28695658}, issn = {1532-6535}, mesh = {Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Inflammatory Bowel Diseases/*therapy ; Randomized Controlled Trials as Topic ; Remission Induction/*methods ; Treatment Outcome ; }, abstract = {The development of new therapies for inflammatory bowel disease is plagued by high costs, potential side effects, and variable levels of effectiveness. Fecal microbial transplant in inflammatory bowel diseases can offer an alternative to traditionally developed pharmacologic therapies and has demonstrated the ability to induce disease remission in randomized control trials. However, questions remain about the ultimate role of this therapy in disease management, including long term safety, and the optimal composition of transplanted stool.}, }
@article {pmid28689671, year = {2018}, author = {Falces-Romero, I and Troyano-Hernáez, P and García-Bujalance, S and Baquero-Artigao, F and Mellado-Peña, MJ and García-Rodríguez, J}, title = {Detection of toxigenic Clostridium difficile in paediatric patients.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {36}, number = {6}, pages = {357-361}, doi = {10.1016/j.eimc.2017.05.006}, pmid = {28689671}, issn = {2529-993X}, mesh = {Adolescent ; Bacterial Proteins/analysis/genetics ; Bacterial Toxins/analysis/genetics ; Cephalosporins/adverse effects/therapeutic use ; Child ; Child, Preschool ; Clostridioides difficile/genetics/*isolation &amp; purification ; Clostridium Infections/epidemiology/*microbiology ; Diarrhea, Infantile/etiology ; Enterocolitis, Pseudomembranous/epidemiology/etiology/microbiology ; Enterotoxins/genetics ; Feces/chemistry ; Female ; Fever/epidemiology/etiology ; Genes, Bacterial ; Humans ; Infant ; Infant, Newborn ; Male ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Tertiary Care Centers/statistics &amp; numerical data ; }, abstract = {INTRODUCTION: Our main objective was a revision of clinical, microbiological and epidemiological results of Clostridium difficile-associated infection in paediatric patients (2010-2015). We compared the diagnoses performed by detection of toxins in feces and those performed by real-time PCR.<br><br>METHODS: This retrospective study included 82 paediatric patients. Detection of toxigenic C. difficile was performed sequentially, in diarrheal feces and under clinical request.<br><br>RESULTS: A total of 39% of the patients were attended at Haematology-oncology Unit and >50% of them had previously received cephalosporins. Fever associated with diarrhea was more frequent in the group of toxin detection, whereas not receiving specific antibiotic treatment was more frequent in the group of positive PCR, without statistically significant differences.<br><br>CONCLUSIONS: We highlight the presence of C. difficile infection in children under 2years old. A diagnostic testing in selected paediatric patients would be advisable when there is clinical suspicion of infection.}, }
@article {pmid28686852, year = {2017}, author = {Kaysen, A and Heintz-Buschart, A and Muller, EEL and Narayanasamy, S and Wampach, L and Laczny, CC and Graf, N and Simon, A and Franke, K and Bittenbring, J and Wilmes, P and Schneider, JG}, title = {Integrated meta-omic analyses of the gastrointestinal tract microbiome in patients undergoing allogeneic hematopoietic stem cell transplantation.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {186}, number = {}, pages = {79-94.e1}, doi = {10.1016/j.trsl.2017.06.008}, pmid = {28686852}, issn = {1878-1810}, mesh = {Adult ; Aged ; Feces/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; *Metabolomics ; Microbiota/*physiology ; Middle Aged ; }, abstract = {In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most notably graft-versus-host disease (GvHD). However, it is presently unknown whether this relationship is causal or consequential. Here, we performed an integrated meta-omic analysis to probe deeper into the GIT microbiome changes during allo-HSCT and its accompanying treatments. We used 16S and 18S rRNA gene amplicon sequencing to resolve archaea, bacteria, and eukaryotes within the GIT microbiomes of 16 patients undergoing allo-HSCT for the treatment of hematologic malignancies. These results revealed a major shift in the GIT microbiome after allo-HSCT including a marked reduction in bacterial diversity, accompanied by only limited changes in eukaryotes and archaea. An integrated analysis of metagenomic and metatranscriptomic data was performed on samples collected from a patient before and after allo-HSCT for acute myeloid leukemia. This patient developed severe GvHD, leading to death 9 months after allo-HSCT. In addition to drastically decreased bacterial diversity, the post-treatment microbiome showed a higher overall number and higher expression levels of antibiotic resistance genes (ARGs). One specific Escherichia coli strain causing a paravertebral abscess was linked to GIT dysbiosis, suggesting loss of intestinal barrier integrity. The apparent selection for bacteria expressing ARGs suggests that prophylactic antibiotic administration may adversely affect the overall treatment outcome. We therefore assert that such analyses including information about the selection of pathogenic bacteria expressing ARGs may assist clinicians in "personalizing" regimens for individual patients to improve overall outcomes.}, }
@article {pmid28685630, year = {2017}, author = {Khajah, MA}, title = {The potential role of fecal microbiota transplantation in the treatment of inflammatory Bowel disease.}, journal = {Scandinavian journal of gastroenterology}, volume = {52}, number = {11}, pages = {1172-1184}, doi = {10.1080/00365521.2017.1347812}, pmid = {28685630}, issn = {1502-7708}, mesh = {Animals ; Dysbiosis/microbiology/therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology/*therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of an unknown etiology. Its pathogenesis involves an interplay of infectious, genetic, environmental, and immunological factors. The current therapeutic options have various limitations in terms of cost, side effect profile, and the development of drug resistance and dependence. Therefore, there is a need to develop future therapeutic options which are safe and effective to control the inflammatory process. This review focuses in a method for the administration of fecal matters (which contains a mixture of various commensals) from a healthy donor to the inflamed colon called fecal microbiota transplantation (FMT) aiming to correct the underlying dysbiosis in the gut as one of the major driving force for the inflammatory process. IBD patients have reduced number of protective (e.g., clostridia and bacteroids) and increased number of pathogenic (e.g., adhesive invasive E. coli and mycobacterium avium paratuberculosis) commensals, and this method is aimed to shift these changes in the gut. Recent studies from animal models and clinical trials suggest promising effects of this method in treating patients with IBD, but more studies are urgently needed to confirm its efficacy and safety, since the etiology of this chronic inflammatory disease is not fully understood and caution should be taken when transplanting fecal matters between individuals which might transfer other infectious organisms and diseases.}, }
@article {pmid28684935, year = {2017}, author = {Lightner, AL and Pemberton, JH}, title = {The Role of Temporary Fecal Diversion.}, journal = {Clinics in colon and rectal surgery}, volume = {30}, number = {3}, pages = {178-183}, pmid = {28684935}, issn = {1531-0043}, abstract = {The use of temporary fecal diversion is of great importance to tenuous anastomosis, immunosuppressed patient, or actively infected patient. Its use protects newly constructed intestinal anastomoses from being the culprit of pelvic sepsis or systemic illness. Thus, potential morbidity and mortality can be averted. However, its appropriate or optimal use is often debated. We herein discuss the evidence for when to best use a diverting stoma for colorectal, coloanal, and ileoanal anastomoses. We also discuss the importance of considering a temporary diverting stoma in the setting of high-dose immunosuppression (e.g., transplant patients or inflammatory bowel disease), active infection, or upon creation of ileal pouch-anal anastomosis. Lastly, we discuss the advantages and disadvantages of a loop ileostomy versus colostomy for temporary diversion of fecal contents.}, }
@article {pmid28684845, year = {2017}, author = {He, Z and Li, P and Zhu, J and Cui, B and Xu, L and Xiang, J and Zhang, T and Long, C and Huang, G and Ji, G and Nie, Y and Wu, K and Fan, D and Zhang, F}, title = {Multiple fresh fecal microbiota transplants induces and maintains clinical remission in Crohn's disease complicated with inflammatory mass.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {4753}, pmid = {28684845}, issn = {2045-2322}, mesh = {Adolescent ; Adult ; Biomarkers ; Cellulitis/diagnostic imaging/microbiology/pathology/*therapy ; Crohn Disease/diagnostic imaging/microbiology/pathology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Remission Induction ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {The ancient Chinese medical literature, as well as our prior clinical experience, suggests that fecal microbiota transplantation (FMT) could treat the inflammatory mass. We aimed to evaluate the efficacy and safety of multiple fresh FMTs for Crohn's disease (CD) complicated with intraabdominal inflammatory mass. The "one-hour FMT protocol" was followed in all patients. Twenty-five patients were diagnosed with CD and related inflammatory mass by CT or MRI. All patients received the initial FMT followed by repeated FMTs every 3 months. The primary endpoint was clinical response (improvement and remission) and sustained clinical remission at 12 months. Secondary endpoints were improvement in size of phegmon/abscess based upon cross-sectional imaging and safety of FMT. 68.0% (17/25) and 52.0% (13/25) of patients achieved clinical response and clinical remission at 3 months post the initial FMT, respectively. The proportion of patients at 6 months, 12 months and 18 months achieving sustained clinical remission with sequential FMTs was 48.0% (12/25), 32.0% (8/25) and 22.7% (5/22), respectively. 9.5% (2/21) of patients achieved radiological healing and 71.4% (15/21) achieved radiological improvement. No severe adverse events related to FMT were observed. This pragmatic study suggested that sequential fresh FMTs might be a promising, safe and effective therapy to induce and maintain clinical remission in CD with intraabdominal inflammatory mass.}, }
@article {pmid28682224, year = {2017}, author = {Debré, P}, title = {[Challenges set by the microbiota].}, journal = {Biologie aujourd'hui}, volume = {211}, number = {1}, pages = {19-28}, doi = {10.1051/jbio/2017012}, pmid = {28682224}, issn = {2105-0686}, mesh = {Animals ; Digestion/physiology ; Disease/*etiology ; Dysbiosis/diet therapy/etiology/microbiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Tract/immunology/microbiology ; Humans ; Immune System/physiology ; Microbiota/*physiology ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; Symbiosis/physiology ; }, abstract = {The microbiota designates the various flora of commensal microbes of living species. Most research in human focusing mainly on the intestinal microbiota, we will limit ourselves to its description and role in physiology and pathology. The intestinal microbiota acts on digestion and the immune system. It seems responsible, at least in part, for obesity, digestive cancers, several autoimmune and allergic pathologies, and pathologies of the nervous system. The role of prebiotics, probiotics, xenobiotics and stool transplantations will be discussed.}, }
@article {pmid28677158, year = {2017}, author = {Shen, Z and Zhu, C and Quan, Y and Yuan, W and Wu, S and Yang, Z and Luo, W and Tan, B and Wang, X}, title = {Update on intestinal microbiota in Crohn's disease 2017: Mechanisms, clinical application, adverse reactions, and outlook.}, journal = {Journal of gastroenterology and hepatology}, volume = {32}, number = {11}, pages = {1804-1812}, doi = {10.1111/jgh.13861}, pmid = {28677158}, issn = {1440-1746}, mesh = {Clostridium Infections/therapy ; Crohn Disease/immunology/*microbiology/*therapy ; Dysbiosis ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Probiotics/administration &amp; dosage ; }, abstract = {The pathogenesis of Crohn's disease (CD) is complex, and it is thought to be associated with the environment, immune, hereditary, microbe, and other factors. If the balance between the host and the intestinal microbes in CD patients was broken, immune-inflammatory response of susceptible individuals might be triggered. Probiotics could improve the intestinal microbial flora balance and treat human effectively. There are several new mechanisms that might explain the role of probiotics. Fecal microbiota transplantation (FMT) is becoming more and more attractive in treating a large amount of digestive system diseases that are related to the dysbiosis of intestinal microbiota. FMT has been widely used in recurrent Clostridium difficile infection. More and more attention has been paid on the clinical application of FMT in CD, while the exact mechanism is still a mystery. So in this review, we explore the mechanism, clinical application, and adverse reactions of intestinal microbiota in CD so that we can use the tool to cure more diseases. Enteric microbiota leads to new therapeutic strategies for CD.}, }
@article {pmid28675277, year = {2016}, author = {Frossard, JL and Moradpour, D}, title = {[Not Available].}, journal = {Revue medicale suisse}, volume = {12}, number = {528}, pages = {1403}, pmid = {28675277}, issn = {1660-9379}, mesh = {*Fecal Microbiota Transplantation ; }, }
@article {pmid28672320, year = {2017}, author = {Gupta, A and Khanna, S}, title = {Fecal Microbiota Transplantation.}, journal = {JAMA}, volume = {318}, number = {1}, pages = {102}, doi = {10.1001/jama.2017.6466}, pmid = {28672320}, issn = {1538-3598}, mesh = {*Fecal Microbiota Transplantation/adverse effects ; Humans ; }, }
@article {pmid28672282, year = {2017}, author = {Ma, GK and Brensinger, CM and Wu, Q and Lewis, JD}, title = {Increasing Incidence of Multiply Recurrent Clostridium difficile Infection in the United States: A Cohort Study.}, journal = {Annals of internal medicine}, volume = {167}, number = {3}, pages = {152-158}, doi = {10.7326/M16-2733}, pmid = {28672282}, issn = {1539-3704}, mesh = {Adolescent ; Adult ; *Clostridioides difficile ; Clostridium Infections/*epidemiology/therapy ; Fecal Microbiota Transplantation ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Risk Factors ; United States/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI), the most common health care-associated infection, often recurs. Fecal microbiota transplantation is increasingly used to treat multiply recurrent CDI (mrCDI).<br><br>OBJECTIVE: To determine whether the incidence of mrCDI is increasing in proportion to CDI and to identify risk factors for mrCDI.<br><br>DESIGN: Retrospective cohort study.<br><br>SETTING: United States.<br><br>PARTICIPANTS: 38&#xa0;911&#xa0;718 commercially insured patients in the OptumInsight Clinformatics Database, of whom 45&#xa0;341 developed CDI.<br><br>MEASUREMENTS: Age- and sex-standardized incidence rates for CDI and mrCDI.<br><br>RESULTS: From 2001 to 2012, the annual incidence of CDI and mrCDI per 1000 person-years increased by 42.7% (from 0.4408 to 0.6289 case) and 188.8% (from 0.0107 to 0.0309 case), respectively. The increase in mrCDI incidence was independent of known risk factors for CDI. Those who developed mrCDI were older (median age, 56.0 vs. 49.0 years; adjusted odds ratio [aOR] per 10-year increase in age, 1.25 [95% CI, 1.21 to 1.29]) and were more likely to be female (63.8% vs. 58.7%; aOR, 1.24 [CI, 1.11 to 1.38]) and to have used antibiotics (72.3% vs. 58.8%; aOR, 1.79 [CI, 1.59 to 2.01]), proton-pump inhibitors (24.6% vs. 18.2%; aOR, 1.14 [CI, 1.01 to 1.29]), or corticosteroids (18.3% vs. 13.7%; aOR, 1.15 [CI, 1.00 to 1.32]) within 90 days of CDI diagnosis. Chronic kidney disease (10.4% vs. 5.6%; aOR, 1.49 [CI, 1.24 to 1.80]) and diagnosis in a nursing home (2.1% vs. 0.6%; aOR, 1.99 [CI, 1.34 to 2.93]) were also associated with increased risk for mrCDI.<br><br>LIMITATION: The primary analyses included only commercially insured patients in the United States.<br><br>CONCLUSION: Relative to CDI, mrCDI incidence has disproportionately increased, indicating a rising demand for mrCDI therapies.<br><br>PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases.}, }
@article {pmid28668658, year = {2018}, author = {Ghoshal, U and Jain, V and Dey, A and Ranjan, P}, title = {Evaluation of enzyme linked immunosorbent assay for stool antigen detection for the diagnosis of cryptosporidiosis among HIV negative immunocompromised patients in a tertiary care hospital of northern India.}, journal = {Journal of infection and public health}, volume = {11}, number = {1}, pages = {115-119}, doi = {10.1016/j.jiph.2017.06.007}, pmid = {28668658}, issn = {1876-035X}, mesh = {Antigens, Protozoan/*analysis ; Cryptosporidiosis/*diagnosis ; Diagnostic Tests, Routine/*methods ; Enzyme-Linked Immunosorbent Assay/*methods ; Feces/chemistry/*parasitology ; Humans ; *Immunocompromised Host ; India ; Microscopy ; Predictive Value of Tests ; Sensitivity and Specificity ; Tertiary Care Centers ; }, abstract = {The diagnosis of cryptosporidiosis among HIV positive patients has been the focus of many studies worldwide. However, there is a paucity of data on HIV negative immunocompromised patients like post-renal transplant recipients and those with haematological malignancies. Stool microscopy, the conventional method of diagnosis, is fraught with difficulties like cumbersome sample processing and subjective interpretation. Enzyme linked immunosorbent assay (ELISA), on the other hand, is quicker and easier. The present study was conducted in a tertiary care and super speciality hospital of north India. Stool specimens from HIV negative immunocompromised patients were subjected to both modified acid fast staining for oocysts of Cryptosporidium and ELISA for detection of Cryptosporidium copro-antigen, over a period of six years. Of the 637 specimens evaluated, 97 (15.23%) samples were positive for Cryptosporidium by both techniques; 25 (3.92%) specimens were positive by ELISA and negative by microscopy, 14 (2.20%) specimens were positive by microscopy but negative by ELISA, while 501 (78.65%) specimens were negative for Cryptosporidium by both techniques. Significant correlation was observed as a measure of agreement (Kappa test value 0.795) between modified ZN stained microscopy and ELISA for the detection of Cryptosporidium oocysts. The sensitivity, specificity, positive and negative predictive value of ELISA, keeping stool microscopy as gold standard were 87.38%, 95.25%, 87.39% and 97.28% respectively. We conclude that ELISA may be used as a reliable substitute for microscopy in setups where the case load is higher or expertise in special staining techniques is not available. The cost of the kit can be justified if the sample load is sufficiently high or if immunocompromised patients form a significant patient population.}, }
@article {pmid28667683, year = {2018}, author = {Mark-Christensen, A and Erichsen, R and Brandsborg, S and Pachler, FR and Nørager, CB and Johansen, N and Pachler, JH and Thorlacius-Ussing, O and Kjaer, MD and Qvist, N and Preisler, L and Hillingsø, J and Rosenberg, J and Laurberg, S}, title = {Pouch failures following ileal pouch-anal anastomosis for ulcerative colitis.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {20}, number = {1}, pages = {44-52}, doi = {10.1111/codi.13802}, pmid = {28667683}, issn = {1463-1318}, mesh = {Adult ; Cohort Studies ; Colitis, Ulcerative/*surgery ; Colonic Pouches/*adverse effects ; Denmark ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Postoperative Complications/epidemiology/*etiology ; Proctocolectomy, Restorative/*adverse effects ; Proportional Hazards Models ; Registries ; Risk Factors ; Young Adult ; }, abstract = {AIM: Ileal pouch-anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain the risk factors associated with failure.<br><br>METHOD: The study included 1991 patients with ulcerative colitis who underwent ileal pouch-anal anastomosis in Denmark in the period 1980-2013. Pouch failure was defined as excision of the pouch or presence of an unreversed stoma within 1&#xa0;year after its creation. We used Cox proportional hazards regression to explore the association between pouch failure and age, gender, synchronous colectomy, primary faecal diversion, annual hospital volume (very low, 1-5 cases per year; low, 6-10; intermediate 11-20; high >&#xa0;20), calendar year, laparoscopy and primary sclerosing cholangitis.<br><br>RESULTS: Over a median 11.4&#xa0;years, 295 failures occurred, corresponding to 5-, 10- and 20-year cumulative risks of 9.1%, 12.1% and 18.2%, respectively. The risk of failure was higher for women [adjusted hazard ratio (aHR) 1.39, 95% CI 1.10-1.75]. Primary non-diversion (aHR 1.63, 95% CI 1.11-2.41) and a low hospital volume (aHR, very low volume vs high volume 2.30, 95% CI 1.26-4.20) were also associated with a higher risk of failure. The risk of failure was not associated with calendar year, primary sclerosing cholangitis, synchronous colectomy or laparoscopy.<br><br>CONCLUSION: In a cohort of patients from Denmark (where pouch surgery is centralized) with ulcerative colitis and ileal pouch-anal anastomosis, women had a higher risk of pouch failure. Of modifiable factors, low hospital volume and non-diversion were associated with a higher risk of pouch failure.}, }
@article {pmid28660835, year = {2017}, author = {Meister, FA and Amygdalos, I and Neumann, UP and Lurje, G}, title = {Rectal foreign body insertion as a rare cause of persistent lumbosacral plexus injury.}, journal = {Annals of the Royal College of Surgeons of England}, volume = {99}, number = {6}, pages = {e191-e192}, pmid = {28660835}, issn = {1478-7083}, mesh = {Aged ; Fecal Incontinence ; *Foreign Bodies/complications/diagnostic imaging/surgery ; Humans ; Ileostomy ; Lumbosacral Plexus/*injuries ; Male ; Peripheral Nerve Injuries/*etiology ; Proctoscopy ; *Rectum/diagnostic imaging/injuries/surgery ; Urinary Incontinence ; }, abstract = {Rectal foreign body insertion is a common condition in emergency surgery, which often requires surgical intervention. Here we report a clinical case of rectal foreign body insertion as a rare cause of persistent lumbosacral plexus injury. A 72-year-old man presented to the emergency department complaining of acute bilateral paraplegia with loss of sensation in both legs, as well as total urinary retention. The patient underwent abdominal computed tomography, which showed a rectal foreign body measuring 13 × 11.5 × 10 cm in the lower abdomen and pelvis. Extraluminal assistance through a median laparotomy was required after unsuccessful attempts at transanal recovery alone. After removal of the foreign body, the rectal wall and anorectal sphincter were massively dilated, with severe bruising of the rectal mucosa on proctoscopy. A protective loop-ileostomy was performed. The sacral plexus is located posteriorly in the pelvis. Physiologically, the nerves are well protected by surrounding anatomical structures. Post-traumatic lumbosacral plexus injuries with paraplegia, urinary retention and anorectal sphincter insufficiency occur quite frequently after heavy traffic accidents. Lumbosacral plexus injury as a result of rectal foreign body insertion is rare. Severe neurological deficits through rectal foreign body insertion are rare but known medical conditions. To the best of our knowledge, this is the first reported case of severe and persistent post-traumatic lumbosacral plexus injury through a rectal foreign body.}, }
@article {pmid28660775, year = {2017}, author = {Neish, AS and Pacifici, R and Mulle, JG and Kraft, CS and Stephens, DS}, title = {The microbiome: current and future view of an ancient paradigm.}, journal = {Future microbiology}, volume = {12}, number = {}, pages = {831-834}, doi = {10.2217/fmb-2017-0083}, pmid = {28660775}, issn = {1746-0921}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/standards ; Dysbiosis/diagnosis/etiology/therapy ; Fecal Microbiota Transplantation ; Host-Pathogen Interactions ; Humans ; *Microbiota ; Probiotics/therapeutic use ; }, }
@article {pmid28656322, year = {2017}, author = {Thaiss, CA and Elinav, E}, title = {The remedy within: will the microbiome fulfill its therapeutic promise?.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {95}, number = {10}, pages = {1021-1027}, pmid = {28656322}, issn = {1432-1440}, mesh = {Animals ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {The last decade of research has witnessed a tremendous upsurge in our understanding of the intestinal microbiome and its role in a large range of human diseases, which has incited hopes for a rapid clinical utilization of the new insights for the development of microbiome-based therapies. Nonetheless, only a single microbiome-targeted therapy has so far found its way into clinical routine: fecal microbiota transplantation for patients suffering from recurrent Clostridium difficile infections. Herein, we discuss the current hopes, advances, challenges, and obstacles for translating basic microbiome research into therapeutic applications for a larger number of diseases and provide an outline of how such clinical applications might emerge.}, }
@article {pmid28652796, year = {2017}, author = {Lane, ER and Zisman, TL and Suskind, DL}, title = {The microbiota in inflammatory bowel disease: current and therapeutic insights.}, journal = {Journal of inflammation research}, volume = {10}, number = {}, pages = {63-73}, pmid = {28652796}, issn = {1178-7031}, abstract = {Inflammatory bowel disease is a heterogeneous group of chronic disorders that result from the interaction of the intestinal immune system with the gut microbiome. Until recently, most investigative efforts and therapeutic breakthroughs were centered on understanding and manipulating the altered mucosal immune response that characterizes these diseases. However, more recent studies have highlighted the important role of environmental factors, and in particular the microbiota, in disease onset and disease exacerbation. Advances in genomic sequencing technology and bioinformatics have facilitated an explosion of investigative inquiries into the composition and function of the intestinal microbiome in health and disease and have advanced our understanding of the interplay between the gut microbiota and the host immune system. The gut microbiome is dynamic and changes with age and in response to diet, antibiotics and other environmental factors, and these alterations in the microbiome contribute to disease onset and exacerbation. Strategies to manipulate the microbiome through diet, probiotics, antibiotics or fecal microbiota transplantation may potentially be used therapeutically to influence modulate disease activity. This review will characterize the factors involved in the development of the intestinal microbiome and will describe the typical alterations in the microbiota that are characteristic of inflammatory bowel disease. Additionally, this manuscript will summarize the early but promising literature on the role of the gut microbiota in the pathogenesis of inflammatory bowel disease with implications for utilizing this data for diagnostic or therapeutic application in the clinical management of patients with these diseases.}, }
@article {pmid28652664, year = {2017}, author = {Halkjær, SI and Boolsen, AW and Günther, S and Christensen, AH and Petersen, AM}, title = {Can fecal microbiota transplantation cure irritable bowel syndrome?.}, journal = {World journal of gastroenterology}, volume = {23}, number = {22}, pages = {4112-4120}, pmid = {28652664}, issn = {2219-2840}, mesh = {Fecal Microbiota Transplantation/adverse effects ; Feces/*microbiology ; Humans ; Intestines/*microbiology ; Irritable Bowel Syndrome/diagnosis/microbiology/*therapy ; Remission Induction ; Treatment Outcome ; }, abstract = {AIM: To verify the utility of treatment with fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS).<br><br>METHODS: We searched EMBASE, Cochrane Library and PubMed in March, 2017. The reviewed literature was based on two systematic searches in each of the databases. The MeSH terms used were IBS and fecal microbiota transplantation and the abbreviations IBS and FMT. Reference lists from the articles were reviewed to identify additional pertinent articles.<br><br>RESULTS: A total of six conference abstracts, one case report, one letter to the editor, and one clinical review were included. In the final analysis, treatment of 48 patients was evaluated. Treatment revealed an improvement in 58% of cases. The varying structure of the nine included studies must be taken into consideration.<br><br>CONCLUSION: Data on FMT and IBS are too limited to draw sufficient conclusions. Standardized double blinded randomized clinical trials need to be carried out to evaluate the effect of FMT on IBS.}, }
@article {pmid28649413, year = {2017}, author = {Kumar, R and Yi, N and Zhi, D and Eipers, P and Goldsmith, KT and Dixon, P and Crossman, DK and Crowley, MR and Lefkowitz, EJ and Rodriguez, JM and Morrow, CD}, title = {Identification of donor microbe species that colonize and persist long term in the recipient after fecal transplant for recurrent Clostridium difficile.}, journal = {NPJ biofilms and microbiomes}, volume = {3}, number = {}, pages = {12}, pmid = {28649413}, issn = {2055-5008}, support = {P30 AI027767/AI/NIAID NIH HHS/United States ; P30 CA013148/CA/NCI NIH HHS/United States ; UL1 TR001417/TR/NCATS NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation has been shown to be an effective treatment for patients with recurrent C. difficile colitis. Although fecal microbiota transplantation helps to re-establish a normal gut function in patients, the extent of the repopulation of the recipient microbial community varies. To further understand this variation, it is important to determine the fate of donor microbes in the patients following fecal microbiota transplantation. We have developed a new method that utilizes the unique single nucleotide variants of gut microbes to accurately identify microbes in paired fecal samples from the same individual taken at different times. Using this method, we identified transplant donor microbes in seven recipients 3-6 months after fecal microbiota transplantation; in two of these fecal microbiota transplantation, we were able to identify donor microbes that persist in recipients up to 2 years post-fecal microbiota transplantation. Our study provides new insights into the dynamics of the reconstitution of the gastrointestinal microbe community structure following fecal microbiota transplantation.}, }
@article {pmid28646951, year = {2017}, author = {Chen, B and Avinashi, V and Dobson, S}, title = {Fecal microbiota transplantation for recurrent clostridium difficile infection in children.}, journal = {The Journal of infection}, volume = {74 Suppl 1}, number = {}, pages = {S120-S127}, doi = {10.1016/S0163-4453(17)30202-5}, pmid = {28646951}, issn = {1532-2742}, mesh = {Adolescent ; Child ; Child, Preschool ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods/*statistics &amp; numerical data ; Humans ; Infant ; *Secondary Prevention ; Treatment Outcome ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is a relatively simple, promising treatment for recurrent Clostridium difficile infection. While there are a wide variety of approaches including mode of delivery, the results are nonetheless encouraging, even amongst younger children. Experience with FMT in the pediatric population is increasing, showing similar success compared to adults. This article will provide an overview of C. difficile infection along with review of the rationale, methods and complications of FMT including the current experience of FMT in children.}, }
@article {pmid28637803, year = {2017}, author = {Fischer, DD and Kandasamy, S and Paim, FC and Langel, SN and Alhamo, MA and Shao, L and Chepngeno, J and Miyazaki, A and Huang, HC and Kumar, A and Rajashekara, G and Saif, LJ and Vlasova, AN}, title = {Protein Malnutrition Alters Tryptophan and Angiotensin-Converting Enzyme 2 Homeostasis and Adaptive Immune Responses in Human Rotavirus-Infected Gnotobiotic Pigs with Human Infant Fecal Microbiota Transplant.}, journal = {Clinical and vaccine immunology : CVI}, volume = {24}, number = {8}, pages = {}, pmid = {28637803}, issn = {1556-679X}, support = {R01 AI099451/AI/NIAID NIH HHS/United States ; }, mesh = {*Adaptive Immunity ; Angiotensin-Converting Enzyme 2 ; Animals ; B-Lymphocytes/immunology ; Diarrhea/virology ; Fecal Microbiota Transplantation ; Germ-Free Life ; Homeostasis ; Humans ; Immunoglobulin A/immunology ; Infant ; Microbiota ; Peptidyl-Dipeptidase A/blood/*metabolism ; Protein Deficiency/*complications ; Rotavirus/immunology/isolation &amp; purification/physiology ; Rotavirus Infections/*complications/immunology/metabolism ; Sus scrofa ; T-Lymphocytes/immunology ; Tryptophan/blood/*metabolism ; }, abstract = {Malnutrition leads to increased morbidity and is evident in almost half of all deaths in children under the age of 5 years. Mortality due to rotavirus diarrhea is common in developing countries where malnutrition is prevalent; however, the relationship between malnutrition and rotavirus infection remains unclear. In this study, gnotobiotic pigs transplanted with the fecal microbiota of a healthy 2-month-old infant were fed protein-sufficient or -deficient diets and infected with virulent human rotavirus (HRV). After human rotavirus infection, protein-deficient pigs had decreased human rotavirus antibody titers and total IgA concentrations, systemic T helper (CD3[+] CD4[+]) and cytotoxic T (CD3[+] CD8[+]) lymphocyte frequencies, and serum tryptophan and angiotensin I-converting enzyme 2. Additionally, deficient-diet pigs had impaired tryptophan catabolism postinfection compared with sufficient-diet pigs. Tryptophan supplementation was tested as an intervention in additional groups of fecal microbiota-transplanted, rotavirus-infected, sufficient- and deficient-diet pigs. Tryptophan supplementation increased the frequencies of regulatory (CD4[+] or CD8[+] CD25[+] FoxP3[+]) T cells in pigs on both the sufficient and the deficient diets. These results suggest that a protein-deficient diet impairs activation of the adaptive immune response following HRV infection and alters tryptophan homeostasis.}, }
@article {pmid28630433, year = {2017}, author = {Sun, LY and Yang, YS and Qu, W and Zhu, ZJ and Wei, L and Ye, ZS and Zhang, JR and Sun, XY and Zeng, ZG}, title = {Gut microbiota of liver transplantation recipients.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {3762}, pmid = {28630433}, issn = {2045-2322}, mesh = {Adult ; *Bacteria/classification/genetics/growth &amp; development ; End Stage Liver Disease/*microbiology/surgery ; Female ; *Gastrointestinal Microbiome ; Humans ; *Liver Transplantation ; Male ; Middle Aged ; RNA, Bacterial/*genetics ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients with end-stage liver disease. Here, we focused on the characteristics of intestinal fecal microbial communities in post-liver transplantation (LT) patients in comparison with those in the same individuals pre-LT and in healthy individuals. The fecal microbial communities were analyzed via MiSeq-PE250 sequencing of the V4 region of 16S ribosomal RNA and were then compared between groups. We found that the gut microbiota of patients with severe liver disease who were awaiting LT was significantly different from that of healthy controls, as represented by the first principal component (p = 0.0066). Additionally, the second principal component represented a significant difference in the gut microbiota of patients between pre-LT and post-LT surgery (p = 0.03125). After LT, there was a significant decrease in the abundance of certain microbial species, such as Actinobacillus, Escherichia, and Shigella, and a significant increase in the abundance of other microbial species, such as Micromonosporaceae, Desulfobacterales, the Sarcina genus of Eubacteriaceae, and Akkermansia. Based on KEGG profiles, 15 functional modules were enriched and 21 functional modules were less represented in the post-LT samples compared with the pre-LT samples. Our study demonstrates that fecal microbial communities were significantly altered by LT.}, }
@article {pmid28630341, year = {2017}, author = {Cao, D and Cao, QM and Subramaniam, S and Yugo, DM and Heffron, CL and Rogers, AJ and Kenney, SP and Tian, D and Matzinger, SR and Overend, C and Catanzaro, N and LeRoith, T and Wang, H and Piñeyro, P and Lindstrom, N and Clark-Deener, S and Yuan, L and Meng, XJ}, title = {Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {27}, pages = {6914-6923}, pmid = {28630341}, issn = {1091-6490}, support = {R01 AI050611/AI/NIAID NIH HHS/United States ; R01 AI074667/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; CD8-Positive T-Lymphocytes/*immunology/metabolism/pathology ; Chronic Disease ; Cytokines/blood/immunology ; Disease Models, Animal ; Hepatitis E/blood/chemically induced/*immunology ; Hepatitis E virus/*immunology/metabolism ; Humans ; *Immunity, Cellular ; *Immunocompromised Host ; Immunosuppressive Agents/adverse effects/pharmacology ; Swine ; Th1 Cells/*immunology/metabolism/pathology ; Th2 Cells/*immunology/metabolism/pathology ; gamma-Glutamyltransferase/blood/immunology ; }, abstract = {Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ-specific CD4[+] T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α-specific CD8[+] T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E.}, }
@article {pmid28628918, year = {2017}, author = {Mizuno, S and Masaoka, T and Naganuma, M and Kishimoto, T and Kitazawa, M and Kurokawa, S and Nakashima, M and Takeshita, K and Suda, W and Mimura, M and Hattori, M and Kanai, T}, title = {Bifidobacterium-Rich Fecal Donor May Be a Positive Predictor for Successful Fecal Microbiota Transplantation in Patients with Irritable Bowel Syndrome.}, journal = {Digestion}, volume = {96}, number = {1}, pages = {29-38}, pmid = {28628918}, issn = {1421-9867}, mesh = {Adult ; Bifidobacterium/*isolation &amp; purification ; Colonoscopy ; Dysbiosis/etiology/microbiology/psychology/*therapy ; Fecal Microbiota Transplantation/*adverse effects ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestines/microbiology ; Irritable Bowel Syndrome/complications/microbiology/psychology/*therapy ; Japan ; *Living Donors ; Male ; Middle Aged ; Treatment Outcome ; }, abstract = {BACKGROUND/AIMS: Dysbiosis is associated with various systemic disorders including irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) might restore intestinal microbial balance. The study aimed to determine the safety and efficacy of FMT in IBS patients, as well as also positive predictors for FMT.<br><br>METHODS: This was a single-arm, open-label study. Eligible patients were diagnosed based on Rome III Diagnostic Criteria. Fecal materials were administered to the patient via colonoscopy. The primary end point was a change in the Bristol stool form scale at 4 weeks after FMT. Recovery to types 3-4 was considered a clinical response. The secondary end point was a change in intestinal microbiota and psychological status using the Hamilton Rating Scale.<br><br>RESULTS: Ten patients were enrolled. Six patients achieved a clinical response. The diversity of patients 4 weeks after FMT increased significantly compared with patients before FMT, and that of responding patients was significantly higher than non-responder patients. The abundance of Bifidobacterium in effective donors was significantly higher than in ineffective donors and patients. Psychological status of all patients was significantly improved after FMT.<br><br>CONCLUSIONS: FMT for patients with IBS is safe, and relatively effective. Bifidobacterium-rich fecal donor may be a positive predictor for successful FMT. Key Summary: (1) Dysbiosis is associated with various gastrointestinal disorders including IBS. (2) FMT has potential to restore intestinal microbial balance. (3) We showed that FMT improved stool form and psychological status of IBS patients. (4) Bifidobacterium-rich donor efficiently induced symbiosis in IBS patients.}, }
@article {pmid28626231, year = {2017}, author = {Sommer, F and Anderson, JM and Bharti, R and Raes, J and Rosenstiel, P}, title = {The resilience of the intestinal microbiota influences health and disease.}, journal = {Nature reviews. Microbiology}, volume = {15}, number = {10}, pages = {630-638}, pmid = {28626231}, issn = {1740-1534}, mesh = {Dysbiosis/*microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Homeostasis/*physiology ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Intestines/*microbiology/physiology ; }, abstract = {The composition of the intestinal microbiota varies among individuals and throughout development, and is dependent on host and environmental factors. However, although the microbiota is constantly exposed to environmental challenges, its composition and function in an individual are stable against perturbations, as microbial communities are resilient and resistant to change. The maintenance of a beneficial microbiota requires a homeostatic equilibrium within microbial communities, and also between the microorganisms and the intestinal interface of the host. The resilience of the healthy microbiota protects us from dysbiosis-related diseases, such as inflammatory bowel disease (IBD) or metabolic disorder. By contrast, a resilient dysbiotic microbiota may cause disease. In this Opinion article, we propose that microbial resilience has a key role in health and disease. We will discuss the concepts and mechanisms of microbial resilience against dietary, antibiotic or bacteriotherapy-induced perturbations and the implications for human health.}, }
@article {pmid28624575, year = {2017}, author = {Botschuijver, S and Roeselers, G and Levin, E and Jonkers, DM and Welting, O and Heinsbroek, SEM and de Weerd, HH and Boekhout, T and Fornai, M and Masclee, AA and Schuren, FHJ and de Jonge, WJ and Seppen, J and van den Wijngaard, RM}, title = {Intestinal Fungal Dysbiosis Is Associated With Visceral Hypersensitivity in Patients With Irritable Bowel Syndrome and Rats.}, journal = {Gastroenterology}, volume = {153}, number = {4}, pages = {1026-1039}, doi = {10.1053/j.gastro.2017.06.004}, pmid = {28624575}, issn = {1528-0012}, mesh = {Abdominal Pain/*microbiology/physiopathology/prevention &amp; control/psychology ; Adult ; Animals ; Antifungal Agents/pharmacology ; Anxiety, Separation/psychology ; Behavior, Animal ; Case-Control Studies ; Cell Degranulation/drug effects ; Cell Line ; Disease Models, Animal ; Dysbiosis ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Fungi/drug effects/*growth &amp; development ; *Gastrointestinal Microbiome/drug effects ; Humans ; Hyperalgesia/*microbiology/physiopathology/prevention &amp; control/psychology ; Intestinal Mucosa/metabolism ; Intestines/innervation/*microbiology ; Irritable Bowel Syndrome/*microbiology/physiopathology/prevention &amp; control/psychology ; Male ; Mast Cells/drug effects/metabolism ; Maternal Deprivation ; Middle Aged ; Pain Measurement ; Pain Perception ; Pain Threshold ; Protein Kinase Inhibitors/pharmacology ; Rats, Long-Evans ; Syk Kinase/antagonists &amp; inhibitors/metabolism ; beta-Glucans/pharmacology ; }, abstract = {BACKGROUND &amp; AIMS: Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity.<br><br>METHODS: We used internal transcribed spacer 1-based metabarcoding to compare fecal mycobiomes of 18 healthy volunteers with those of 39 patients with IBS (with visceral hypersensitivity or normal levels of sensitivity). We also compared the mycobiomes of Long-Evans rats separated from their mothers (hypersensitive) with non-handled (normally sensitive) rats. We investigated whether fungi can cause visceral hypersensitivity using rats exposed to fungicide (fluconazole and nystatin). The functional relevance of the gut mycobiome was confirmed in fecal transplantation experiments: adult maternally separated rats were subjected to water avoidance stress (to induce visceral hypersensitivity), then given fungicide and donor cecum content via oral gavage. Other rats subjected to water avoidance stress were given soluble &#x3b2;-glucans, which antagonize C-type lectin domain family 7 member A (CLEC7A or DECTIN1) signaling via spleen-associated tyrosine kinase (SYK), a SYK inhibitor to reduce visceral hypersensitivity, or vehicle (control). The sensitivity of mast cells to fungi was tested with mesenteric windows (ex&#xa0;vivo) and the human mast cell line HMC-1.<br><br>RESULTS: &#x3b1; diversity (Shannon index) and mycobiome signature (stability selection) of both groups of IBS patients differed from healthy volunteers, and the mycobiome signature of hypersensitive patients differed from that of normally sensitive patients. We observed mycobiome dysbiosis in rats that had been separated from their mothers compared with non-handled rats. Administration of fungicide to hypersensitive rats reduced their visceral hypersensitivity to normal levels of sensitivity. Administration of cecal mycobiomes from rats that had been separated from their mothers (but not non-handled mycobiome) restored hypersensitivity to distension. Administration of soluble &#x3b2;-glucans or a SYK inhibitor reduced visceral hypersensitivity, compared with controls. Particulate &#x3b2;-glucan (a DECTIN-1 agonist) induced mast cell degranulation in mesenteric windows and HMC-1 cells responded to fungal antigens by release of histamine.<br><br>CONCLUSIONS: In an analysis of patients with IBS and controls, we associated fungal dysbiosis with IBS. In studies of rats, we found fungi to promote visceral hypersensitivity, which could be reduced by administration of fungicides, soluble &#x3b2;-glucans, or a SYK inhibitor. The intestinal fungi might therefore be manipulated for treatment of IBS-related visceral hypersensitivity.}, }
@article {pmid28623952, year = {2017}, author = {Kouam, C and Passang, O and Guifo, ML and Atem, N}, title = {Spontaneous cecal perforation in a 40-year-old pregnant woman treated by primary repair and omental patch: a case report.}, journal = {Journal of medical case reports}, volume = {11}, number = {1}, pages = {162}, pmid = {28623952}, issn = {1752-1947}, mesh = {Adult ; Cecal Diseases/diagnosis/*surgery ; Female ; Humans ; Intestinal Perforation/diagnosis/*surgery ; *Laparotomy ; Omentum/*transplantation ; Peritonitis/diagnostic imaging/*surgery ; Pregnancy ; Pregnancy Complications/diagnosis/*surgery ; Suture Techniques ; Treatment Outcome ; }, abstract = {BACKGROUND: Spontaneous colonic perforations are scarce, and cecal perforations even more so. Preoperative diagnosis of the latter in a pregnant woman is particularly difficult because of physiologic changes and restrictions on some diagnostic imaging techniques, such as X-rays. Furthermore, management of these patients is a big challenge.<br><br>CASE PRESENTATION: We present a case of a spontaneous cecal perforation in a 40-year-old pregnant black woman in the Regional Hospital of Bafoussam in Cameroon. The results of clinical examination and ultrasonography on admission were in line with acute generalized peritonitis in a woman at 20&#xa0;weeks of a viable pregnancy, indicating an urgent laparotomy. Operative findings were a 1&#x2009;&#xd7;&#x2009;1-cm perforation on a distended cecum with minimal fecal contamination. The treatment consisted of excision of the edges, primary suture of the perforation, and omentoplasty. The recovery of the patient was uneventful.<br><br>CONCLUSIONS: The management of spontaneous cecal perforation in a pregnant woman was a big challenge. The perforation was repaired by primary suture and omentoplasty. Further studies comparing this approach with right hemicolectomy are recommended.}, }
@article {pmid28617055, year = {2017}, author = {Panés, J and Alfaro, I}, title = {New treatment strategies for ulcerative colitis.}, journal = {Expert review of clinical immunology}, volume = {13}, number = {10}, pages = {963-973}, doi = {10.1080/1744666X.2017.1343668}, pmid = {28617055}, issn = {1744-8409}, mesh = {Adrenal Cortex Hormones/*therapeutic use ; Aminosalicylic Acids/*therapeutic use ; Antibodies, Monoclonal/*therapeutic use ; Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Quality of Life ; }, abstract = {Therapeutic strategies in ulcerative colitis are evolving. A personalized and optimal use of available drugs and the integration of new drug classes are the cornerstones underpinning the new treatment paradigms. Areas covered: A structured literature search in Medline and PubMed, Cochrane meta-analyses, and abstracts of international congresses has been performed to review therapeutic approaches to ulcerative colitis. The primary therapeutic objective of therapy is to achieve clinical remission since persistence of active disease, even if mild, leads to a significant reduction in quality of life. Current treatment paradigms of ulcerative colitis are based on the use of 5-aminosalycilates, corticosteroids, thiopurines, TNF-α inhibitors and α4ß7 integrin blockers. The main determinants for drug class selection are disease extension, disease severity, and previous drug history. New drug classes that will likely become available in the foreseeable future include inhibitors of Janus kinases, modulators of sphingosine-1-phosphate receptors, SMAD-7 antisense oligonucleotides, interleukin-12/23 blockers, and fecal microbiota transplantation. Expert commentary: Increasing therapeutic options for ulcerative colitis make predictors of response highly relevant. While these are not available, judicious use of therapies, avoidance of underdosing, or persistent therapy when criteria for drug failure are met are essential.}, }
@article {pmid28615387, year = {2017}, author = {Schreiber, RA and Butler, A}, title = {Screening for biliary atresia: it's in the cards.}, journal = {Canadian family physician Medecin de famille canadien}, volume = {63}, number = {6}, pages = {424-425}, pmid = {28615387}, issn = {1715-5258}, mesh = {Biliary Atresia/*diagnosis ; Bilirubin/blood ; *Early Diagnosis ; Feces ; Humans ; Infant, Newborn ; Neonatal Screening/*methods ; Parents ; }, }
@article {pmid28612983, year = {2017}, author = {Costello, SP and Soo, W and Bryant, RV and Jairath, V and Hart, AL and Andrews, JM}, title = {Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {46}, number = {3}, pages = {213-224}, doi = {10.1111/apt.14173}, pmid = {28612983}, issn = {1365-2036}, mesh = {Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces ; Humans ; Randomized Controlled Trials as Topic ; Remission Induction ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods.<br><br>AIM: To determine whether FMT is effective and safe for the induction of remission in active UC.<br><br>METHODS: Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs).<br><br>RESULTS: There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission.<br><br>CONCLUSIONS: Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent.}, }
@article {pmid28611478, year = {2017}, author = {Dickson, I}, title = {Therapy: Bacteriophages important for FMT efficacy.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {14}, number = {7}, pages = {386}, pmid = {28611478}, issn = {1759-5053}, mesh = {*Bacteriophages ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; Treatment Outcome ; }, }
@article {pmid28609775, year = {2017}, author = {Biedermann, L}, title = {Vancomycin in Very-Early Onset Inflammatory Bowel Disease-Dysbiosis: Fight Fire with Fire?.}, journal = {Digestion}, volume = {95}, number = {4}, pages = {327-328}, doi = {10.1159/000477088}, pmid = {28609775}, issn = {1421-9867}, mesh = {Age Factors ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Dysbiosis/etiology/microbiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Humans ; Inflammatory Bowel Diseases/etiology/microbiology/*therapy ; Treatment Outcome ; Vancomycin/pharmacology/*therapeutic use ; }, }
@article {pmid28609252, year = {2017}, author = {de Groot, PF and Frissen, MN and de Clercq, NC and Nieuwdorp, M}, title = {Fecal microbiota transplantation in metabolic syndrome: History, present and future.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {253-267}, pmid = {28609252}, issn = {1949-0984}, support = {//CIHR/Canada ; }, mesh = {Animals ; Atherosclerosis/microbiology/therapy ; Clostridium Infections/therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation/*trends ; Feces/microbiology ; Gastrointestinal Microbiome ; *Host-Pathogen Interactions ; Humans ; Inflammation/therapy ; Inflammatory Bowel Diseases/microbiology/therapy ; Insulin Resistance ; Intestines/microbiology ; Metabolic Syndrome/microbiology/*therapy ; Non-alcoholic Fatty Liver Disease/microbiology/therapy ; Randomized Controlled Trials as Topic ; }, abstract = {The history of fecal microbiota transplantation (FMT) dates back even to ancient China. Recently, scientific studies have been looking into FMT as a promising treatment of various diseases, while in the process teaching us about the interaction between the human host and its resident microbial communities. Current research focuses mainly on Clostridium difficile infections, however interest is rising in other areas such as inflammatory bowel disease (IBD) and the metabolic syndrome. With regard to the latter, the intestinal microbiota might be causally related to the progression of insulin resistance and diabetes. FMT in metabolic syndrome has proven to be an intriguing method to study the role of the gut microbiota and open the way to new therapies by dissecting in whom insulin resistance is driven by microbiota. In this article we review the history of FMT, the present evidence on its role in the pathophysiology of metabolic syndrome and its efficacy, limitations and future prospects.}, }
@article {pmid28609251, year = {2017}, author = {Weingarden, AR and Vaughn, BP}, title = {Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {238-252}, pmid = {28609251}, issn = {1949-0984}, mesh = {Animals ; Clostridium Infections/therapy ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Helminthiasis/therapy ; Humans ; Inflammatory Bowel Diseases/*therapy ; Intestines/microbiology ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease (IBD) is a complex set of diseases that lead to chronic inflammation in the gastrointestinal tract. Although the etiology of IBD is not fully understood, it is well-known that the intestinal microbiota is associated with the development and maintenance of IBD. Manipulation of the gut microbiota, therefore, may represent a target for IBD therapy. Fecal microbiota transplantation (FMT), where fecal microbiota from a healthy donor is transplanted into a patient's GI tract, is already a successful therapy for Clostridium difficile infection. FMT is currently being explored as a potential therapy for IBD as well. In this review, the associations between the gut microbiota and IBD and the emerging data on FMT for IBD will be discussed.}, }
@article {pmid28607413, year = {2017}, author = {Xiao, Y and Yan, H and Diao, H and Yu, B and He, J and Yu, J and Zheng, P and Mao, X and Luo, Y and Chen, D}, title = {Early Gut Microbiota Intervention Suppresses DSS-Induced Inflammatory Responses by Deactivating TLR/NLR Signalling in Pigs.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {3224}, pmid = {28607413}, issn = {2045-2322}, mesh = {Animals ; Colitis/chemically induced/*genetics/metabolism ; Cytokines/metabolism ; Dextran Sulfate ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Gene Expression ; Genotype ; NLR Proteins/*genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/*genetics ; Species Specificity ; Swine/classification/*genetics/metabolism ; Toll-Like Receptors/*genetics/metabolism ; }, abstract = {Recent metagenomic studies suggest that innate and adaptive immune phenotypes can be programmed via gut microbiota-host interactions mediated via activation of pattern recognition receptors (PRRs) on host cells. In this study, we used two extremely different pig lines (the Yorkshire and the Tibetan) to test the hypothesis that the transplantation of gut microbiota could transfer certain immunologic characteristics from donor to recipient. The faecal microbiota of these two pig lines was transplanted in healthy commercial hybrid newborn piglets to establish the "Tibetan-intervened" and "Yorkshire-intervened" porcine models. Then, acute colitis was induced using dextran sulphate sodium (DSS), which activated Toll-/NOD-like receptor (TLR/NLR) signalling in the colonic tissues of the "Yorkshire-intervened" piglets, leading to increases in pro-inflammatory cytokines and immune cells and causing intestinal injuries. Conversely, DSS administration had little influence on the "Tibetan-intervened" piglets, which showed no significant inflammation and no changes in cytokines, immune cells, or signalling molecules, including TLRs, NLRs, MYD88 and NF-κB, after DSS treatment. These results indicate that pigs inoculated with the Tibetan microbiota acquired relatively strong resistance to experimental colitis, suggesting that the genotype of the host contributes to the uniqueness of its intestinal microbial community, whereas the microbiota plays a vital role in programming the immune phenotypes of the host.}, }
@article {pmid28602517, year = {2017}, author = {Tang, G and Yin, W and Liu, W}, title = {Is frozen fecal microbiota transplantation as effective as fresh fecal microbiota transplantation in patients with recurrent or refractory Clostridium difficile infection: A meta-analysis?.}, journal = {Diagnostic microbiology and infectious disease}, volume = {88}, number = {4}, pages = {322-329}, doi = {10.1016/j.diagmicrobio.2017.05.007}, pmid = {28602517}, issn = {1879-0070}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Clostridioides difficile/pathogenicity ; Clostridium Infections/*microbiology/*therapy ; Fecal Microbiota Transplantation/methods ; Feces/*microbiology ; Female ; Freezing ; Humans ; Male ; Microbiota/physiology ; Middle Aged ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is a remarkably efficacious therapy for recurrent or refractory Clostridium difficile infection (CDI), but not standardized. This work is to determine whether frozen FMT is as effective as fresh FMT. Meta-analysis showed that frozen FMT was as effective as fresh FMT, both pooled first effective rate (65.0% (95% CI 57.0-73.0%) vs. 65.0% (95% CI 57.0-73.0%), P=0.962) and pooled second effective rate (95.0% (95% CI 91.0-99.0%) vs. 95.0% (95% CI 92.0-99.0%), P=0.880). In conclusion, among patients with recurrent or refractory CDI, frozen FMT is as effective as fresh FMT. Considering potential advantages of performing frozen FMT, it is a reasonable option to select frozen FMT.}, }
@article {pmid28601577, year = {2017}, author = {Davido, B and Batista, R and Fessi, H and Salomon, J and Dinh, A}, title = {Impact of faecal microbiota transplantation to eradicate vancomycin-resistant enterococci (VRE) colonization in humans.}, journal = {The Journal of infection}, volume = {75}, number = {4}, pages = {376-377}, doi = {10.1016/j.jinf.2017.06.001}, pmid = {28601577}, issn = {1532-2742}, mesh = {Anti-Bacterial Agents ; *Fecal Microbiota Transplantation ; Gram-Positive Bacterial Infections ; Humans ; Vancomycin ; *Vancomycin-Resistant Enterococci ; }, }
@article {pmid28596693, year = {2017}, author = {He, Z and Cui, BT and Zhang, T and Li, P and Long, CY and Ji, GZ and Zhang, FM}, title = {Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report.}, journal = {World journal of gastroenterology}, volume = {23}, number = {19}, pages = {3565-3568}, pmid = {28596693}, issn = {2219-2840}, mesh = {Crohn Disease/*complications/*therapy ; Epilepsy/*complications/*therapy ; *Fecal Microbiota Transplantation ; Feces ; Female ; Gastrointestinal Microbiome ; Humans ; Intestines/microbiology/physiopathology ; Quality of Life ; Recurrence ; Remission Induction ; Seizures ; Treatment Outcome ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising strategy that involves reconstruction of gut microbiota. Recently, it has been considered as a treatment of Crohn's disease (CD) and certain neurological diseases. Here, to the best of our knowledge, we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy. During the 20 mo of follow-up, FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs. Furthermore, this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota.}, }
@article {pmid28595295, year = {2017}, author = {Dinh, A and Duran, C and Bouchand, F and Salomon, J and Davido, B}, title = {Fecal Microbiota Transplantation Is a New Effective Weapon to Fight Multidrug-Resistant Bacteria, but Harmonization and More Data Are Needed.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {8}, pages = {1425-1426}, doi = {10.1093/cid/cix538}, pmid = {28595295}, issn = {1537-6591}, mesh = {*Anti-Bacterial Agents ; Bacteria ; *Fecal Microbiota Transplantation ; Humans ; Prospective Studies ; Weapons ; }, }
@article {pmid28592766, year = {2017}, author = {Kakihana, K}, title = {[Fecal microbiota transplantation for acute graft-versus-host disease of the gut].}, journal = {[Rinsho ketsueki] The Japanese journal of clinical hematology}, volume = {58}, number = {5}, pages = {499-505}, doi = {10.11406/rinketsu.58.499}, pmid = {28592766}, issn = {0485-1439}, mesh = {Acute Disease ; Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Graft vs Host Disease/*therapy ; Humans ; Intestinal Diseases/microbiology/*therapy ; }, abstract = {Advances in microbial analysis have provided new insights into the complex interactions between the host and gut microbiota. An imbalance in the gut microbiota (dysbiosis) is associated with various disorders and their pathogenesis. Furthermore, in allogeneic stem cell transplantation, increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (GVHD) and transplant outcomes, suggesting that its manipulation could be a new treatment strategy for this acute condition. We conducted a feasibility study of fecal microbiota transplantation (FMT) for acute GVHD of the gut in four human transplant recipients. No severe adverse events that were obviously attributable to FMT were observed. All patients responded to FMT: three patients showed a complete response and one a partial response. Our results indicate that FMT could be a new treatment option for acute GVHD of the gut. However, the use of FMT in treating acute GVHD is in the initial stages of clinical application. FMT has limitations that need to be addressed, such as safety and determination of the optimal donor screening or the treatment protocol. Further evaluation is thus warranted.}, }
@article {pmid28589214, year = {2017}, author = {Solbach, P and Dersch, P and Bachmann, O}, title = {[Individualized treatment strategies for Clostridium difficile infections].}, journal = {Der Internist}, volume = {58}, number = {7}, pages = {675-681}, pmid = {28589214}, issn = {1432-1289}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; *Clostridioides difficile ; Clostridium Infections/*drug therapy/mortality ; Fecal Microbiota Transplantation ; Female ; Fidaxomicin ; Humans ; Metronidazole/*therapeutic use ; Recurrence ; Secondary Prevention ; Vancomycin/*therapeutic use ; }, abstract = {Upon hospitalization, up to 15.5% of patients are already colonized with a toxigenic Clostridium difficile strain (TCD). The rate of asymptomatic colonization is 0-3% in healthy adults and up to 20-40% in hospitalized patients. The incidence and mortality of C. difficile infection (CDI) has significantly increased during recent years. Mortality lies between 3 and 14%. CDI is generally caused by intestinal dysbiosis, which can be triggered by various factors, including antibiotics or immune suppressants. If CDI occurs, ongoing antibiotic therapy should be discontinued. The choice of treatment is guided by the clinical situation: Mild courses of CDI should be treated with metronidazole. Oral vancomycin is suitable as a first-line therapy of mild CDI occurring during pregnancy and lactation, as well as in cases of intolerance or allergy to metronidazole. Severe courses should be treated with vancomycin. Recurrence should be treated with vancomycin or fidaxomicin. Multiple recurrences should be treated with vancomycin or fidaxomicin; if necessary, a vancomycin taper regimen may also be used. An alternative is fecal microbiota transplant (FMT), with healing rates of more than 80%. Bezlotoxumab is the first available monoclonal antibody which neutralizes the C. difficile toxin B, and in combination with an antibiotic significantly reduces the rate of a new C. difficile infection compared to placebo. A better definition of clinical and microbiota-associated risk factors and the ongoing implementation of molecular diagnostics are likely to lead to optimized identification of patients at risk, and an increasing individualization of prophylactic and therapeutic approaches.}, }
@article {pmid28588566, year = {2017}, author = {Tidjani Alou, M and Million, M and Traore, SI and Mouelhi, D and Khelaifia, S and Bachar, D and Caputo, A and Delerce, J and Brah, S and Alhousseini, D and Sokhna, C and Robert, C and Diallo, BA and Diallo, A and Parola, P and Golden, M and Lagier, JC and Raoult, D}, title = {Gut Bacteria Missing in Severe Acute Malnutrition, Can We Identify Potential Probiotics by Culturomics?.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {899}, pmid = {28588566}, issn = {1664-302X}, abstract = {Severe acute malnutrition is the world-leading cause of children under-five's death. Recent metagenomics studies have established a link between gut microbiota and severe acute malnutrition, describing an immaturity with a striking depletion in oxygen-sensitive prokaryotes. Amoxicillin and therapeutic diet cure most of the children with severe acute malnutrition but an irreversible disruption of the gut microbiota is suspected in the refractory and most severe cases. In these cases, therapeutic diet may be unable to reverse the microbiota alteration leading to persistent impaired development or death. In addition, as enteric sepsis is a major cause of death in this context, identification of missing gut microbes to be tested as probiotics (live bacteria that confer a benefit to the host) to restore rapidly the healthy gut microbiota and prevent the gut pathogenic invasion is of foremost importance. In this study, stool samples of malnourished patients with kwashiorkor and healthy children were collected from Niger and Senegal and analyzed by culturomics and metagenomics. We found a globally decreased diversity, a decrease in the hitherto unknown diversity (new species isolation), a depletion in oxygen-sensitive prokaryotes including Methanobrevibacter smithii and an enrichment in potentially pathogenic Proteobacteria, Fusobacteria and Streptococcus gallolyticus. A complex of 12 species identified only in healthy children using culturomics and metagenomics were identified as probiotics candidates, providing a possible, defined, reproducible, safe, and convenient alternative to fecal transplantation to restore a healthy gut microbiota in malnourished children. Microbiotherapy based on selected strains has the potential to improve the current treatment of severe acute malnutrition and prevent relapse and death by reestablishing a healthy gut microbiota.}, }
@article {pmid28586116, year = {2017}, author = {Bajaj, JS and Kassam, Z and Fagan, A and Gavis, EA and Liu, E and Cox, IJ and Kheradman, R and Heuman, D and Wang, J and Gurry, T and Williams, R and Sikaroodi, M and Fuchs, M and Alm, E and John, B and Thacker, LR and Riva, A and Smith, M and Taylor-Robinson, SD and Gillevet, PM}, title = {Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial.}, journal = {Hepatology (Baltimore, Md.)}, volume = {66}, number = {6}, pages = {1727-1738}, pmid = {28586116}, issn = {1527-3350}, support = {I01 CX001076/CX/CSRD VA/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; Cognition ; *Fecal Microbiota Transplantation ; Female ; Hepatic Encephalopathy/*therapy ; Humans ; Male ; Metabolome ; Microbiota ; Middle Aged ; Treatment Outcome ; }, abstract = {UNLABELLED: Recurrent hepatic encephalopathy (HE) is a leading cause of readmission despite standard of care (SOC) associated with microbial dysbiosis. Fecal microbiota transplantation (FMT) may improve dysbiosis; however, it has not been studied in HE. We aimed to define whether FMT using a rationally derived stool donor is safe in recurrent HE compared to SOC alone. An open-label, randomized clinical trial with a 5-month follow-up in outpatient men with cirrhosis with recurrent HE on SOC was conducted with 1:1 randomization. FMT-randomized patients received 5 days of broad-spectrum antibiotic pretreatment, then a single FMT enema from the same donor with the optimal microbiota deficient in HE. Follow-up occurred on days 5, 6, 12, 35, and 150 postrandomization. The primary outcome was safety of FMT compared to SOC using FMT-related serious adverse events (SAEs). Secondary outcomes were adverse events, cognition, microbiota, and metabolomic changes. Participants in both arms were similar on all baseline criteria and were followed until study end. FMT with antibiotic pretreatment was well tolerated. Eight (80%) SOC participants had a total of 11 SAEs compared to 2 (20%) FMT participants with SAEs (both FMT unrelated; P = 0.02). Five SOC and no FMT participants developed further HE (P = 0.03). Cognition improved in the FMT, but not the SOC, group. Model for End-Stage Liver Disease (MELD) score transiently worsened postantibiotics, but reverted to baseline post-FMT. Postantibiotics, beneficial taxa, and microbial diversity reduction occurred with Proteobacteria expansion. However, FMT increased diversity and beneficial taxa. SOC microbiota and MELD score remained similar throughout.<br><br>CONCLUSION: FMT from a rationally selected donor reduced hospitalizations, improved cognition, and dysbiosis in cirrhosis with recurrent HE. (Hepatology 2017;66:1727-1738).}, }
@article {pmid28583769, year = {2018}, author = {Allegretti, JR and Kassam, Z and Osman, M and Budree, S and Fischer, M and Kelly, CR}, title = {The 5D framework: a clinical primer for fecal microbiota transplantation to treat Clostridium difficile infection.}, journal = {Gastrointestinal endoscopy}, volume = {87}, number = {1}, pages = {18-29}, doi = {10.1016/j.gie.2017.05.036}, pmid = {28583769}, issn = {1097-6779}, mesh = {*Clostridioides difficile ; Contraindications, Procedure ; Directive Counseling ; *Donor Selection ; Enterocolitis, Pseudomembranous/diagnosis/*therapy ; Fecal Microbiota Transplantation/*adverse effects/methods ; Humans ; Patient Discharge ; Patient Education as Topic ; Patient Participation ; *Patient Selection ; }, }
@article {pmid28576475, year = {2017}, author = {Yoshioka, K and Kakihana, K and Doki, N and Ohashi, K}, title = {Gut microbiota and acute graft-versus-host disease.}, journal = {Pharmacological research}, volume = {122}, number = {}, pages = {90-95}, doi = {10.1016/j.phrs.2017.05.028}, pmid = {28576475}, issn = {1096-1186}, mesh = {Acute Disease ; Animals ; Dysbiosis/*complications/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Graft vs Host Disease/etiology/*microbiology/therapy ; Humans ; Probiotics/therapeutic use ; Stem Cell Transplantation/adverse effects ; }, abstract = {Although allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for various hematological diseases, acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality, and its management is clinically important. Advances in biological techniques have led to great progress in understanding the complex interactions between the host and the gut microbiota. The gut microbiota clearly modulates the immune response and is associated with the pathogenesis of various disorders. Also in allo-SCT, both preclinical and clinical results indicate that the gut microbiota is closely associated with the development of acute GVHD and transplant outcomes. These results led to the idea that improvement in quantitative and/or qualitative abnormalities of microbiota (dysbiosis) may be a new treatment strategy for acute GVHD. Evaluations of therapies targeting the gut microbiota such as probiotics or fecal microbiota transplantation have just begun. Furthermore, intervention in the gut microbiota with a nutritional approach including prebiotics, postbiotics, and antibiotics selection may also be another promising treatment option for acute GVHD.}, }
@article {pmid28576434, year = {2017}, author = {Tashk, P and Lecronier, M and Clermont, O and Renvoisé, A and Aubry, A and Barrou, B and Hertig, A and Lescat, M and Tenaillon, O and Denamur, E and Tourret, J}, title = {[Molecular epidemiology and kinetics of early Escherichia coli urinary tract infections in kidney transplant recipients].}, journal = {Nephrologie &amp; therapeutique}, volume = {13}, number = {4}, pages = {236-244}, doi = {10.1016/j.nephro.2016.10.008}, pmid = {28576434}, issn = {1872-9177}, mesh = {DNA, Bacterial/isolation &amp; purification ; Escherichia coli/*growth &amp; development ; Escherichia coli Infections/*epidemiology ; Feces/microbiology ; Female ; France/epidemiology ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Opportunistic Infections/*microbiology ; Polymerase Chain Reaction ; *Transplant Recipients ; Urinary Tract Infections/*microbiology ; }, abstract = {BACKGROUND: Escherichia coli strains causing Urinary Tract Infections (UTI) have a fecal origin.<br><br>METHODS: A fecal sample was collected before Kidney Transplantation (KT) and concomitantly with urine at each of the 15 E. coli UTIs which occurred in 11 KT recipients. Unique E.&#xa0;coli strains were identified among 25 isolates per feces and 5 isolates per urinary sample by random amplification of polymorphic DNA. Phylogenetic group (which is correlated to virulence in the E.&#xa0;coli species) was determined for each E.&#xa0;coli strain by a PCR based method.<br><br>RESULTS: Forty-three unique fecal strains and 14 unique urinary strains were identified among 650 fecal isolates and 75 urinary isolates. Urinary strains frequently (55% of the cases) belonged to a phylogroup usually not linked to virulence. They were detected in the feces collected concomitantly in 60% of the cases. Urinary strains belonging to a phylogroup usually linked to virulence were more frequently dominant in the feces (100%) than urinary strains belonging to a non-pathogenic phylogroup (42%; P<0.05). Vesical catheter was a facilitating factor only for urinary strains belonging to non-pathogenic phylogroups. Thirty-three percent of the fecal strains were persisting in two consecutive fecal samples and 62% were detected for the first time at the UTI. Numerous pathway lead to UTIs: from a unique, virulent and persisting strain to a non-virulent recently acquired strain facilitated by a vesical catheter.<br><br>CONCLUSION: Our work shows the diversity of host-microbial interactions which precede extra-intestinal virulence.}, }
@article {pmid28575220, year = {2017}, author = {Patron, RL and Hartmann, CA and Allen, S and Griesbach, CL and Kosiorek, HE and DiBaise, JK and Orenstein, R}, title = {Vancomycin Taper and Risk of Failure of Fecal Microbiota Transplantation in Patients With Recurrent Clostridium difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {7}, pages = {1214-1217}, doi = {10.1093/cid/cix511}, pmid = {28575220}, issn = {1537-6591}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*drug effects ; Clostridium Infections/*drug therapy ; Fecal Microbiota Transplantation/methods ; Feces/*microbiology ; Female ; Humans ; Male ; Microbiota/physiology ; Middle Aged ; Recurrence ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Vancomycin/*therapeutic use ; Young Adult ; }, abstract = {We retrospectively analyzed a cohort of 109 subjects treated for recurrent Clostridium difficile infection with fecal microbiota transplantation (FMT) at a tertiary referral center between 2011 and 2014 to determine risk factors for FMT failure. In a multivariate analysis, failure to use an oral vancomycin taper preceding FMT was associated with a significant risk of FMT failure (odds ratio, 0.15; 95% confidence interval, .007-.40).}, }
@article {pmid28574663, year = {2017}, author = {Andjelkov, K and Sforza, M and Barisic, G and Soldatovic, I and Hiranyakas, A and Krivokapic, Z}, title = {A novel method for treatment of chronic anal fissure: adipose-derived regenerative cells - a pilot study.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {19}, number = {6}, pages = {570-575}, doi = {10.1111/codi.13555}, pmid = {28574663}, issn = {1463-1318}, mesh = {Adipose Tissue/*cytology ; Adult ; Anal Canal/*physiology/transplantation ; Chronic Disease ; Feasibility Studies ; Female ; Fissure in Ano/complications/*therapy ; Humans ; Male ; Middle Aged ; Pain/etiology ; Pain Measurement ; Pilot Projects ; Prospective Studies ; *Regeneration ; Stem Cell Transplantation/*methods ; Transplantation, Autologous ; Treatment Outcome ; }, abstract = {AIM: The purpose of this study was to investigate the safety and feasibility of autologous adipose-derived regenerative cells (ADRC) in the treatment of chronic anal fissure.<br><br>METHOD: A prospective pilot study was conducted in six patients with chronic anal fissures at the First Surgical Clinic, Clinical Center of Serbia and at the BelPrime Clinic, Belgrade, Serbia. All patients were candidates for surgical treatment. The average duration of symptoms was 24&#xa0;months. Pain assessment was quantified using a visual analogue scale and bowel continence was assessed using the Wexner incontinence score. Both were assessed before treatment and during each postoperative outpatient visit. Liposuction was performed under local or general anaesthesia. Extraction of ADRC was achieved with a closed automated medical device. The fat and ADRC were injected subcutaneously into the edge of the fissure. The rest of the pellet was infiltrated into the internal anal sphincter. The study has been registered at ClinicalTrials.gov (NCT02628522).<br><br>RESULTS: Complete healing of the anal fissure and the disappearance of symptoms was achieved in all patients. The average time to complete pain cessation was 33.7&#xa0;&#xb1;&#xa0;15.0&#xa0;days. All fissures healed after 3&#xa0;months and remained healed 12&#xa0;months after the procedure. There were no complications related to the procedure.<br><br>CONCLUSION: The application of ADRC may be an alternative to lateral sphincterotomy and a reliable procedure which avoids faecal incontinence.}, }
@article {pmid28572754, year = {2017}, author = {Gaci, N and Chaudhary, PP and Tottey, W and Alric, M and Brugère, JF}, title = {Functional amplification and preservation of human gut microbiota.}, journal = {Microbial ecology in health and disease}, volume = {28}, number = {1}, pages = {1308070}, pmid = {28572754}, issn = {0891-060X}, abstract = {Background: The availability of fresh stool samples is a prerequisite in most gut microbiota functional studies. Objective: Strategies for amplification and long-term gut microbiota preservation from fecal samples would favor sample sharing, help comparisons and reproducibility over time and between laboratories, and improve the safety and ethical issues surrounding fecal microbiota transplantations. Design: Taking advantage of in vitro gut-simulating systems, we amplified the microbial repertoire of a fresh fecal sample and assessed the viability and resuscitation of microbes after preservation with some common intracellular and extracellular acting cryoprotective agents (CPAs), alone and in different combinations. Preservation efficiencies were determined after 3 and 6 months and compared with the fresh initial microbiota diversity and metabolic activity, using the chemostat-based Environmental Control System for Intestinal Microbiota (ECSIM) in vitro model of the gut environment. Microbial populations were tested for fermentation gas, short-chain fatty acids, and composition of amplified and resuscitated microbiota, encompassing methanogenic archaea. Results: Amplification of the microbial repertoire from a fresh fecal sample was achieved with high fidelity. Dimethylsulfoxide, alone or mixed with other CPAs, showed the best efficiency for functional preservation, and the duration of preservation had little effect. Conclusions: The amplification and resuscitation of fecal microbiota can be performed using specialized in vitro gut models. Correct amplification of the initial microbes should ease the sharing of clinical samples and improve the safety of fecal microbiota transplantation. Abbreviations: CDI, Clostridium difficile infection; CPA, cryoprotective agent; D, DMSO, dimethylsulfoxide; FMT, fecal microbiota transplantation; G, glycerol; IBD, inflammatory bowel disease; P, PEG-4000, polyethylene glycol 4000 g.mol[-1]; SCFA, short-chain fatty acid; SNR, signal-to-noise ratio.}, }
@article {pmid28572645, year = {2017}, author = {Youngster, I and Gerding, DN}, title = {Editorial: Making Fecal Microbiota Transplantation Easier to Swallow: Freeze-Dried Preparation for Recurrent Clostridium difficile Infections.}, journal = {The American journal of gastroenterology}, volume = {112}, number = {6}, pages = {948-950}, pmid = {28572645}, issn = {1572-0241}, mesh = {*Clostridioides difficile ; Clostridium Infections/microbiology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Microbiota ; }, abstract = {Fecal microbiota transplant (FMT) has emerged as an effective and increasingly popular therapy for recurrent Clostridium difficile infections in patients that have failed standard antimicrobial treatment. Patient access to FMT is hampered by the logistics of manufacturing, storing, and delivering the inocula. An observational study describes the development and clinical efficacy of freeze-dried FMT capsules for oral administration. While awaiting the emergence of defined bacterial therapeutics for Clostridium difficile infections, this refinement of FMT is an encouraging step toward simplifying FMT treatment. Randomized controlled trials are required to further establish the efficacy and safety of lyophilized FMT.}, }
@article {pmid28569200, year = {2017}, author = {Yamazaki, Y and Kawarai, S and Morita, H and Kikusui, T and Iriki, A}, title = {Faecal transplantation for the treatment of Clostridium difficile infection in a marmoset.}, journal = {BMC veterinary research}, volume = {13}, number = {1}, pages = {150}, pmid = {28569200}, issn = {1746-6148}, mesh = {Animals ; Callithrix/*microbiology ; *Clostridioides difficile ; Clostridium Infections/therapy/*veterinary ; Fecal Microbiota Transplantation/*veterinary ; Male ; Monkey Diseases/*microbiology/therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: The common marmoset has been used as an experimental animal for various purposes. Because its average weight ranges from 250 to 500 g, weight loss quickly becomes critical for sick animals. Therefore, effective and non-stressful treatment for chronic diseases, including diarrhoea, is essential.<br><br>CASE PRESENTATION: We report a case in which faecal microbiota transplantation (FMT) led to immediate recovery from chronic and recurrent diarrhoea caused by Clostridium difficile infection. A male common marmoset experienced chronic diarrhoea after antibiotic treatments. The animal experienced severe weight loss, and a faecal sample was confirmed to be C. difficile-positive but was negative for protozoa. Metronidazole was partially effective at the first administration but not after the recurrence of the clinical signs. Then, oral FMT was administered to the subject by feeding fresh faeces from healthy individuals mixed with the marmoset's usual food. We monitored the faeces by categorization into four groups: normal, loose, diarrhoea, and watery. After the first day of FMT treatment, the marmoset underwent a remarkable recovery from diarrhoea, and after the fourth day of treatment, a test for C. difficile was negative. The clinical signs did not recur. The marmoset recovered from sinusitis and bilateral dacryocystitis, which also did not recur, as a by-product of the improvement in its general health caused by the cessation of diarrhoea after the FMT.<br><br>CONCLUSION: This is the first reported case of successful treatment of a marmoset using oral FMT. As seen in human patients, FMT was effective for the treatment of recurrent C. difficile infection in a captive marmoset.}, }
@article {pmid28569156, year = {2017}, author = {Ma, Y and Yang, J and Cui, B and Xu, H and Xiao, C and Zhang, F}, title = {How Chinese clinicians face ethical and social challenges in fecal microbiota transplantation: a questionnaire study.}, journal = {BMC medical ethics}, volume = {18}, number = {1}, pages = {39}, pmid = {28569156}, issn = {1472-6939}, mesh = {*Attitude of Health Personnel ; Awareness ; *Bioethical Issues ; China ; Clostridium Infections/*therapy ; Emotions ; *Fecal Microbiota Transplantation/ethics/psychology ; Gastroenterologists ; Gastroenterology ; Humans ; Informed Consent ; *Physician-Patient Relations ; *Physicians ; Privacy ; Surveys and Questionnaires ; Tissue Donors ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is reportedly the most effective therapy for relapsing Clostridium Difficile infection (CDI) and a potential therapeutic option for many diseases. It also poses important ethical concerns. This study is an attempt to assess clinicians' perception and attitudes towards ethical and social challenges raised by fecal microbiota transplantation.<br><br>METHODS: A questionnaire was developed which consisted of 20 items: four items covered general aspects, nine were about ethical aspects such as informed consent and privacy issues, four concerned social and regulatory issues, and three were about an FMT bank. This was distributed to participants at the Second China gastroenterology and FMT conference in May 2015. Basic descriptive statistical analyses and simple comparative statistical tests were performed.<br><br>RESULTS: Nearly three quarters of the 100 respondents were gastro-enterologist physicians. 89% of all respondents believed FMT is a promising treatment modality for some diseases and 88% of whom chose clinical efficacy as the primary reason for recommending FMT. High expectation from patients and pressure on clinicians (33%) was reported as the most frequent reasons for not recommending FMT. The clinicians who had less familiarity with FMT reported significantly more worry related to the dignity and psychological impact of FMT compared to those who have high familiarity with FMT (51.6% vs 27.8%, p&#xa0;=&#xa0;0.021).More than half of the respondents (56.1%) were concerned about the commercialization of FMT, although almost one in five respondents did not see this as a problem.<br><br>CONCLUSIONS: We found most respondents have positive attitudes towards FMT but low awareness of published evidence. Informed consent for vulnerable patients, privacy and protection of donors were perceived as the most challenging ethical aspects of FMT. This study identified areas of limited knowledge and ways of addressing ethical issues and indicates the need to devise the education and training for clinicians on FMT.}, }
@article {pmid28560232, year = {2017}, author = {Chiriac, MT and Mahapatro, M and Neurath, MF and Becker, C}, title = {The Microbiome in Visceral Medicine: Inflammatory Bowel Disease, Obesity and Beyond.}, journal = {Visceral medicine}, volume = {33}, number = {2}, pages = {153-162}, pmid = {28560232}, issn = {2297-4725}, abstract = {It has become increasingly evident over the past two decades that the microbiota plays a nurturing role in the development of the immune system. This appears to be important since the amplitude of immune responses has a crucial regulatory function in homeostasis and the prevention of unwanted inflammation. Hence, a malfunctioning gut flora has been shown to play a key role in visceral medicine. Strong evidence demonstrates for example that intestinal inflammation can develop as a result of a dysregulated microbiota, deficient antimicrobial responses, and aberrant bacterial translocation into the bowel wall. In healthy individuals, the bacterial translocation is blocked by a single layer of highly specialized intestinal epithelial cells which forms a strong barrier that lines the gut wall. This structure is responsible for an efficient absorption of nutrients while keeping the luminal flora at bay. In susceptible individuals, for yet incompletely understood reasons, either defective epithelial barrier function or dysregulated microbial composition or microbial pathogens drive intestinal inflammation. Many therapeutic strategies focusing on the modulation of the microbiota have been proposed recently but future research including prospective human studies and gnotobiotic mouse models are still needed to evaluate the contribution and potential therapeutic value of individual bacteria to human health.}, }
@article {pmid28559695, year = {2017}, author = {Iacob, T and Ţăţulescu, DF and Dumitraşcu, DL}, title = {Therapy of the postinfectious irritable bowel syndrome: an update.}, journal = {Clujul medical (1957)}, volume = {90}, number = {2}, pages = {133-138}, pmid = {28559695}, issn = {1222-2119}, abstract = {After acute infectious gastroenteritis, up to thirty percent of patients present prolonged gastrointestinal symptoms and a part of those affected patients can have the diagnostic criteria for postinfectious irritable bowel syndrome. Treatment is symptom directed rather than curative and includes agents prescribed for the treatment of irritable bowel syndrome in general. Prophylaxis or early treatment of acute bacterial diarrhea may reduce the risk of postinfectious irritable bowel syndrome development by reducing the occurrence, duration, and severity of the chronic inflammation and mucosal alterations (all these believed to play an important role in disease persistence). Probiotic treatment is effective in restoring the intestinal microbiota in patients with irritable bowel syndrome and in animal models there are improvements of postinfectious irritable bowel syndrome. Fecal microbiota transplantation seems to be one of the most effective methods of treating the postinfectious irritable bowel syndrome (with recurrent episodes) caused by Clostridium difficile.}, }
@article {pmid28557822, year = {2017}, author = {de Clercq, NC and Frissen, MN and Groen, AK and Nieuwdorp, M}, title = {Gut Microbiota and the Gut-Brain Axis: New Insights in the Pathophysiology of Metabolic Syndrome.}, journal = {Psychosomatic medicine}, volume = {79}, number = {8}, pages = {874-879}, doi = {10.1097/PSY.0000000000000495}, pmid = {28557822}, issn = {1534-7796}, mesh = {Animals ; *Brain/metabolism ; *Gastrointestinal Microbiome ; Humans ; Metabolic Syndrome/immunology/*metabolism/microbiology ; *Signal Transduction ; }, abstract = {OBJECTIVE: Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut axis in relation to the pathophysiology of metabolic syndrome.<br><br>METHODS: A selective literature review was conducted to evaluate GI and brain interactions.<br><br>RESULTS: Evidence suggests reduced microbial diversity in obesity and metabolic dysregulation. However, findings of microbiota composition in obese individuals are inconsistent, and the investigation of causality between gut microbiota and energy homeostasis is complex because multiple variables contribute to the gut microbiota composition. The microbial metabolites short chain fatty acids are found to exert numerous physiologic effects, including energy homeostasis through the regulation of GI hormones such as cholecystokinin, glucagon-like peptide 1, peptide tyrosine-tyrosine, and leptin. Preclinical studies show that modifying rodents' microbiota through fecal transplantation results in alterations of these GI hormones and subsequently an altered metabolism and behavior. However, whether and to what extent preclinical findings translate to human metabolism is unclear.<br><br>CONCLUSIONS: One of the major limitations and challenges in this field of research is interindividual variability of the microbiome. Future research needs to combine recent insights gained into tracking the dynamics of the microbiome as well as the metabolic responses. Furthermore, advanced mapping of the human microbiome is required to investigate the metabolic implications of the gut-brain axis to develop targeted interventions for obesity and metabolic syndrome.}, }
@article {pmid28550391, year = {2018}, author = {Arab, JP and Martin-Mateos, RM and Shah, VH}, title = {Gut-liver axis, cirrhosis and portal hypertension: the chicken and the egg.}, journal = {Hepatology international}, volume = {12}, number = {Suppl 1}, pages = {24-33}, pmid = {28550391}, issn = {1936-0541}, support = {R01 AA021171/AA/NIAAA NIH HHS/United States ; R01 DK059615/DK/NIDDK NIH HHS/United States ; AASLD/Lifer Clinical and Translational Research Fellowship in Liver Diseases//American Association for the Study of Liver Diseases/ ; R37 AA021171/AA/NIAAA NIH HHS/United States ; R56 DK059615/DK/NIDDK NIH HHS/United States ; P30 DK084567/DK/NIDDK NIH HHS/United States ; R01 DK59615/DK/NIDDK NIH HHS/United States ; }, mesh = {Adrenergic beta-Antagonists/therapeutic use ; Bacterial Infections/complications ; Bacterial Translocation/genetics ; Bile Acids and Salts/metabolism ; Endotoxemia/etiology/metabolism ; Fecal Microbiota Transplantation/adverse effects/methods ; Gastrointestinal Microbiome/*drug effects/genetics ; Hepatic Encephalopathy/complications/microbiology ; Humans ; Hypertension, Portal/*etiology/metabolism/microbiology ; Intestinal Mucosa/metabolism ; Intestines/*microbiology ; Lipopolysaccharide Receptors/metabolism ; Liver/*metabolism ; Liver Cirrhosis/*complications/metabolism/therapy ; Liver Diseases/metabolism/*physiopathology ; Non-alcoholic Fatty Liver Disease/complications/prevention &amp; control/therapy ; Peritonitis/microbiology ; Probiotics/therapeutic use ; Receptors, Cytoplasmic and Nuclear/metabolism ; }, abstract = {The term gut-liver axis is used to highlight the close anatomical and functional relationship between the intestine and the liver. The intestine has a highly specialized epithelial membrane which regulates transport across the mucosa. Due to dysbiosis, impairment of the intestinal barrier and altered immunity status, bacterial products can reach the liver through the portal vein, where they are recognized by specific receptors, activate the immune system and lead to a proinflammatory response. Gut microbiota and bacterial translocation play an important role in the pathogenesis of chronic liver diseases, including alcoholic and non-alcoholic fatty liver disease, cirrhosis, and its complications, such as portal hypertension, spontaneous bacterial peritonitis and hepatic encephalopaty. The gut microbiota also plays a critical role as a modulator of bile acid metabolism which can also influence intestinal permeability and portal hypertension through the farnesoid-X receptor. On the other hand, cirrhosis and portal hypertension affect the microbiota and increase translocation, leading to a "chicken and egg" situation, where translocation increases portal pressure, and vice versa. A myriad of therapies targeting gut microbiota have been evaluated specifically in patients with chronic liver disease. Further studies targeting intestinal microbiota and its possible hemodynamic and metabolic effects are needed. This review summarizes the current knowledge about the role of gut microbiota in the pathogenesis of chronic liver diseases and portal hypertension.}, }
@article {pmid28547892, year = {2017}, author = {Valentini, D and Ianiro, G and Di Bartolo, I and Di Camillo, C and Boccuzzi, E and Vittucci, AC and Ruggeri, FM and Monini, M}, title = {Hospital-acquired rotavirus and norovirus acute gastroenteritis in a pediatric unit, in 2014-2015.}, journal = {Journal of medical virology}, volume = {89}, number = {10}, pages = {1768-1774}, doi = {10.1002/jmv.24866}, pmid = {28547892}, issn = {1096-9071}, mesh = {Acute Disease/epidemiology ; Adolescent ; Caliciviridae Infections/*epidemiology/virology ; Child ; Child, Preschool ; Cross Infection/*epidemiology/virology ; Feces/virology ; Female ; Gastroenteritis/*epidemiology/*virology ; Genotype ; *Hospital Units ; Humans ; Infant ; Italy/epidemiology ; Male ; Mamastrovirus/genetics/isolation &amp; purification ; Norovirus/genetics/isolation &amp; purification ; Norwalk virus/genetics/isolation &amp; purification ; *Pediatrics ; Phylogeny ; Prospective Studies ; RNA, Viral/genetics ; Real-Time Polymerase Chain Reaction ; Rotavirus/genetics/isolation &amp; purification ; Rotavirus Infections/*epidemiology/virology ; Sequence Analysis, DNA ; }, abstract = {The occurrence of hospital-acquired acute gastroenteritis (AGE) is a major concern for public health. RotavirusA (RVA) and norovirus (NoV) are common causes of viral AGE in the pediatric population, and their role in nosocomial infections has been proven, remaining poorly investigated. To investigate RVA and NoV in hospital-acquired AGE, 55 stool samples from children with nosocomial AGE were collected between May 2014 and May 2015. To evaluate virus spreading routes, 51 environmental swabs were collected from staff and patients' rooms. Stools were tested for both RVA and NoV RNA by reverse-transcription-PCR. Nucleotide sequencing and phylogenetic analysis were performed to characterize the viruses. Forty-seven of 55 cases analyzed resulted positive for RVA. The predominant genotype was G4P[8] (18/55) followed by G1P[8] (14/55). Mixed RVA infections were also detected (7/55). Twenty-two samples were positive for NoV, and GII.4 was revealed to be the predominant genotype. Seventeen samples were positive for both RVA and NoV. This study aimed to evaluate the burden of norovirus and rotavirus nosocomial AGE, contributing to identify the environment source of infections and to activate effective strategies for intervention. The reduction in nosocomial AGE cases is an important aspect, considered the worsened disease course in transplant, cancer, and intensive care unit inpatients.}, }
@article {pmid28547076, year = {2017}, author = {Longhi, MS and Moss, A and Jiang, ZG and Robson, SC}, title = {Purinergic signaling during intestinal inflammation.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {95}, number = {9}, pages = {915-925}, pmid = {28547076}, issn = {1432-1440}, support = {P01 HL087203/HL/NHLBI NIH HHS/United States ; R01 HL094400, P01HL107152, P01 HL087203//National Institutes of Health/ ; R01 DK108894//National Institutes of Health/ ; R01 AI132389/AI/NIAID NIH HHS/United States ; R01 HL094400/HL/NHLBI NIH HHS/United States ; R01 DK108894/DK/NIDDK NIH HHS/United States ; P01 HL107152/HL/NHLBI NIH HHS/United States ; }, mesh = {Adenosine/metabolism ; Animals ; Antigens, CD/metabolism ; Apyrase/metabolism ; Biomarkers ; Dysbiosis ; Exosomes/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; Inflammatory Bowel Diseases/etiology/*metabolism/pathology/therapy ; Lymphocytes/immunology/metabolism ; Macrophages/immunology/metabolism ; Purines/*metabolism ; Receptors, Aryl Hydrocarbon/metabolism ; *Signal Transduction ; }, abstract = {Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer. Aberrant purinergic signaling pathways have been implicated in disordered thromboregulation and immune dysregulation, as noted in the pathogenesis of IBD and other gastrointestinal/hepatic autoimmune diseases. Expression of CD39 on endothelial or immune cells allows for homeostatic integration of hemostasis and immunity, which are disrupted in IBD. Our focus in this review is on novel aspects of the functions of CD39 and related NTPDases in IBD. Regulated CD39 activity allows for scavenging of extracellular nucleotides, the maintenance of P2-receptor integrity and coordination of adenosinergic signaling responses. CD39 together with CD73, serves as an integral component of the immunosuppressive machinery of dendritic cells, myeloid cells, T and B cells. Genetic inheritance and environental factors closely regulate the levels of expression and phosphohydrolytic activity of CD39, both on immune cells and released microparticles. Purinergic mechanisms associated with T regulatory and supressor T helper type 17 cells modulate disease activity in IBD, as can be modeled in experimental colitis. As a recent example, upregulation of CD39 is dependent upon ligation of the aryl hydrocarbon receptor (AHR), as with natural ligands such as bilirubin and 2-(1' H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Decreased expression of CD39 and/or dysfunctional AHR signaling, however, abrogates the protective effects of immunosuppressive AHR ligands. These factors could also serve as biomarkers of disease activity in IBD. Heightened thrombosis, inflammation, and immune disturbances as seen in IBD appear to be associated with aberrant purinergic signaling. Ongoing development of therapeutic strategies augmenting CD39 ectonucleotidase bioactivity via cytokines or AHR ligands offers promise for management of thrombophilia, disordered inflammation, and aberrant immune reactivity in IBD.}, }
@article {pmid28546791, year = {2017}, author = {Gianotti, RJ and Moss, AC}, title = {Fecal Microbiota Transplantation: From Clostridium difficile to Inflammatory Bowel Disease.}, journal = {Gastroenterology &amp; hepatology}, volume = {13}, number = {4}, pages = {209-213}, pmid = {28546791}, issn = {1554-7914}, abstract = {Fecal microbiota transplantation (FMT) has evolved from a case report in the medical literature to the basis of major innovations in the treatment of Clostridium difficile infection (CDI) and, potentially, inflammatory bowel disease (IBD). In the clinical setting, FMT was noted to significantly lower the risk of recurrent CDI, likely by increasing microbial diversity and altering the metabolic environment in the intestinal tract of recipients. In parallel, advances in the ability to quantify and characterize microbial communities in fecal samples led to the association of IBD with a state of intestinal dysbiosis. Consequently, a number of case series and randomized, controlled trials have evaluated FMT in treating active ulcerative colitis or Crohn's disease. Unlike in CDI, the efficacy of FMT in the treatment of IBD appears to be influenced by a number of factors, including donor microbial profiles, inflammatory burden, and the microbial diversity of the recipient. The therapeutic potential of the microbiome has led to a number of biotechnology and pharmaceutical companies isolating specific strains from healthy stool for use as targeted therapies for IBD in clinical trials. Ongoing studies are likely to determine the missing link between the efficacy of FMT and its impact on microbial communities and mucosal inflammation.}, }
@article {pmid28546789, year = {2017}, author = {Lichtenstein, GR}, title = {Fecal Microbiota Transplantation: An Update.}, journal = {Gastroenterology &amp; hepatology}, volume = {13}, number = {4}, pages = {203}, pmid = {28546789}, issn = {1554-7914}, }
@article {pmid28545829, year = {2017}, author = {Kang, Y and Cai, Y}, title = {Gut microbiota and hepatitis-B-virus-induced chronic liver disease: implications for faecal microbiota transplantation therapy.}, journal = {The Journal of hospital infection}, volume = {96}, number = {4}, pages = {342-348}, doi = {10.1016/j.jhin.2017.04.007}, pmid = {28545829}, issn = {1532-2939}, mesh = {Dysbiosis/*therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Hepatitis B, Chronic/*complications/*therapy ; Humans ; }, abstract = {Hepatitis B is one of the most common infectious diseases globally. It has been estimated that there are 350 million chronic hepatitis B virus (HBV) carriers worldwide. The liver is connected to the small intestine by the bile duct, which carries bile formed in the liver to the intestine. Nearly all of the blood that leaves the stomach and intestines must pass through the liver. Human intestines contain a wide diversity of microbes, collectively termed the 'gut microbiota'. Gut microbiota play a significant role in host metabolic processes and host immune modulation, and influence host development and physiology (organ development). Altered gut microbiota is a common complication in liver disease. Changes in intestinal microbiota seem to play an important role in induction and promotion of HBV-induced chronic liver disease progression, and specific species among the intestinal commensal bacteria may play either a pathogenic or a protective role in the development of HBV-induced chronic liver disease. Thus, the gut microbiome may represent fertile targets for prevention or management of HBV-induced chronic liver disease. Faecal microbiota transplantation (FMT) may be a useful therapy for HBV-related disease in the future. However, the data available in this field remain limited, and relevant scientific work has only just commenced. New technologies have enabled systematic studies of gut microbiota, and provided more realistic information about its composition and pathological variance. This review summarizes the cutting edge of research into the relationship between gut microbiota and HBV-induced chronic liver disease, and the future prospects of FMT therapy.}, }
@article {pmid28545248, year = {2017}, author = {Wang, JH and Kim, BS and Han, K and Kim, H}, title = {Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {6}, pages = {}, pmid = {28545248}, issn = {1660-4601}, mesh = {Adipose Tissue ; Animals ; Blood Glucose/analysis ; Body Weight ; Cecum/microbiology ; Chemokine CCL2 ; Cytokines/genetics ; Diet, High-Fat ; *Ephedra ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Gene Expression ; Insulin/blood ; Insulin Resistance ; Liver ; Male ; Metabolic Diseases/blood/*therapy ; Obesity/blood/*therapy ; Plant Extracts/*pharmacology ; Rats, Sprague-Dawley ; }, abstract = {Changes in gut microbiota (GM) are closely associated with metabolic syndrome, obesity, type 2 diabetes and so on. Several medicinal herbs, including Ephedra sinica (Es), have anti-obesity effects that ameliorate metabolic disorders. Therefore, in this study we evaluated whether Es maintains its anti-obesity effect through Es-altered gut microbiota (EsM) transplantation. GM was isolated from cecal contents of Es treated and untreated rats following repeated transplants into obese rats via oral gavage over three weeks. High-fat-diet (HFD)-induced obese rats transplanted with EsM lost significant body weight, epididymal fat, and perirenal fat weight, but no remarkable changes were observed in abdominal fat, liver, cecum weight and food efficiency ratio. In addition, treatment with EsM also significantly lowered the fasting blood glucose, serum insulin level, and insulin resistance index. Meanwhile, EsM transplantation significantly reduced gene expression of proinflammatory cytokines interleukin-1 and monocyte chemotactic protein-1. Rats treated with EsM also showed changed GM composition, especially blautia, roseburia and clostridium, significantly reduced the level of endotoxin and markedly increased the acetic acid in feces. Overall, our results demonstrated that EsM ameliorates HFD-induced obesity and related metabolic disorders, like hyperglycemia and insulin resistance, and is strongly associated with modulating the distribution of GM, enterogenous endotoxin and enteral acetic acid.}, }
@article {pmid28543188, year = {2017}, author = {Chitrala, KN and Guan, H and Singh, NP and Busbee, B and Gandy, A and Mehrpouya-Bahrami, P and Ganewatta, MS and Tang, C and Chatterjee, S and Nagarkatti, P and Nagarkatti, M}, title = {CD44 deletion leading to attenuation of experimental autoimmune encephalomyelitis results from alterations in gut microbiome in mice.}, journal = {European journal of immunology}, volume = {47}, number = {7}, pages = {1188-1199}, pmid = {28543188}, issn = {1521-4141}, support = {R01 AI129788/AI/NIAID NIH HHS/United States ; R01 MH094755/MH/NIMH NIH HHS/United States ; R01 ES019313/ES/NIEHS NIH HHS/United States ; P20 GM103641/GM/NIGMS NIH HHS/United States ; P01 AT003961/AT/NCCIH NIH HHS/United States ; R01 AT006888/AT/NCCIH NIH HHS/United States ; R01 AI123947/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteroidetes/genetics/immunology/isolation &amp; purification ; Disease Models, Animal ; Dysbiosis ; Encephalomyelitis, Autoimmune, Experimental/*immunology/physiopathology ; Fatty Acids, Volatile/immunology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Firmicutes/genetics/immunology/isolation &amp; purification ; Gastrointestinal Microbiome/genetics/*immunology ; Gene Deletion ; Hyaluronan Receptors/*genetics/*immunology ; Metagenomics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Propionates/metabolism ; RNA, Ribosomal, 16S ; }, abstract = {Dysbiosis in gut microbiome has been shown to be associated with inflammatory and autoimmune diseases. Previous studies from our laboratory demonstrated the pivotal role played by CD44 in the regulation of EAE, a murine model of multiple sclerosis. In the current study, we determined whether these effects resulted from an alteration in gut microbiota and the short-chain fatty acid (SCFA) production in CD44 knockout (CD44KO) mice. Fecal transfer from naïve CD44KO but not C57BL/6 wild type (CD44WT) mice, into EAE-induced CD44WT mice, led to significant amelioration of EAE. High-throughput bacterial 16S rRNA gene sequencing, followed by clustering sequences into operational taxonomic units (OTUs) and biochemical analysis, revealed that EAE-induced CD44KO mice showed significant diversity, richness, and evenness when compared to EAE-induced CD44WT mice at the phylum level, with dominant Bacteroidetes (68.5%) and low Firmicutes (26.8%). Further, data showed a significant change in the abundance of SCFAs, propionic acid, and i-butyric acid in EAE-CD44KO compared to EAE-CD44WT mice. In conclusion, our results demonstrate that the attenuation of EAE seen following CD44 gene deletion in mice may result from alterations in the gut microbiota and SCFAs. Furthermore, our studies also demonstrate that the phenotype of gene knock-out animals may be shaped by gut microbiota.}, }
@article {pmid28542523, year = {2017}, author = {Zaza, G and Dalla Gassa, A and Felis, G and Granata, S and Torriani, S and Lupo, A}, title = {Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen.}, journal = {PloS one}, volume = {12}, number = {5}, pages = {e0178228}, pmid = {28542523}, issn = {1932-6203}, mesh = {Adult ; Aged ; Everolimus/adverse effects/*therapeutic use ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Humans ; Immunosuppressive Agents/adverse effects/*therapeutic use ; *Kidney Transplantation ; Maintenance Chemotherapy/adverse effects ; Male ; Metagenomics ; Middle Aged ; Mycophenolic Acid/therapeutic use ; Tacrolimus/adverse effects/*therapeutic use ; }, abstract = {BACKGROUND: The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined.<br><br>METHODS: We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols. Nine patients were treated with everolimus plus mycophenolate mofetil (EVE+MMF group), and 11 patients were treated with a standard therapy with tacrolimus plus mycophenolate mofetil (TAC+MMF group).<br><br>RESULTS: A statistical analysis of comparative high-throughput data demonstrated that although similar according to the degree of Shannon diversity (alpha diversity) at the taxonomic level, three functional genes clearly discriminated EVE+MMF versus TAC+MMF (cutoff: log2 fold change&#x2265;1, FDR&#x2264;0.05). Flagellar motor switch protein (fliNY) and type IV pilus assembly protein pilM (pilM) were significantly enriched in TAC+MMF-treated patients, while macrolide transport system mrsA (msrA) was more abundant in patients treated with EVE+MMF. Finally, PERMANOVA revealed that among the variables analyzed and included in our model, only the consumption of sugar significantly influenced beta diversity.<br><br>CONCLUSIONS: Our study, although performed on a relatively small number of patients, showed, for the first time, specific immunosuppressive-related effects on fecal microbiome of renal transplant recipients and it suggested that the analysis of the gut microbes community could represent a new tool to better understand the effects of drugs currently employed in organ transplantations. However, multicenter studies including healthy controls should be undertaken to better address this objective.}, }
@article {pmid28542111, year = {2017}, author = {Nanayakkara, D and Nanda, N}, title = {Clostridium difficile infection in solid organ transplant recipients.}, journal = {Current opinion in organ transplantation}, volume = {22}, number = {4}, pages = {314-319}, doi = {10.1097/MOT.0000000000000430}, pmid = {28542111}, issn = {1531-7013}, mesh = {Clostridioides difficile/*pathogenicity ; Clostridium Infections/*etiology/pathology ; Humans ; Organ Transplantation/*adverse effects/mortality ; Risk Factors ; Survival Analysis ; Transplant Recipients ; }, abstract = {PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is a major healthcare-associated infection that causes significant morbidity and an economic impact in the United States. In this review, we provide an overview of Clostridium difficile infection in solid organ transplant recipients with an emphasis on recent literature.<br><br>RECENT FINDINGS: C. difficile in solid organ transplant population has unique risk factors. Fecal microbiota transplantation has shown favorable results in treatment of recurrent C. difficile in this population. Preliminary data from animal studies suggests excellent efficacy with immunization against C. difficile toxins.<br><br>SUMMARY: Over the last decade, number of individuals receiving solid organ transplants has increased exponentially making peri-transplant complications a common occurrence.C. difficile is a frequent cause of morbidity in solid organ transplant recipients. Early and accurate diagnosis of C. difficile requires a stepwise approach. Differentiating between asymptomatic carriage and infection is a diagnostic challenge. Microbial diversity is inversely proportional to risk of C. difficile infection. Antimicrobial stewardship programs help to retain microbial diversity in individuals susceptible to CDI. Recurrent or relapsing C. difficile infection require fecal microbiota transplantation for definitive cure.}, }
@article {pmid28541799, year = {2017}, author = {Vujkovic-Cvijin, I and Rutishauser, RL and Pao, M and Hunt, PW and Lynch, SV and McCune, JM and Somsouk, M}, title = {Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals.}, journal = {Gut microbes}, volume = {8}, number = {5}, pages = {440-450}, pmid = {28541799}, issn = {1949-0984}, support = {P30 AI027763/AI/NIAID NIH HHS/United States ; R21 DK104664/DK/NIDDK NIH HHS/United States ; T32 AI060530/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Dysbiosis/*therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; HIV Infections/*complications ; Humans ; Male ; Middle Aged ; Treatment Outcome ; }, abstract = {Many HIV-infected individuals on antiretroviral therapy (ART) exhibit persistent systemic inflammation, which predicts morbidity and mortality. ART-treated subjects concurrently exhibit marked compositional alterations in the gut bacterial microbiota and the degree of dysbiosis correlates with systemic inflammation. Whether interventions to modulate the microbiome can affect systemic inflammation is unknown. An open-label fecal microbial transplantation (FMT) was delivered by colonoscopy to asymptomatic HIV-infected ART-suppressed individuals without antibiotic pre-treatment. Stool was assessed before and after FMT for engraftment of donor microbes, and peripheral blood was assayed for immune activation biomarkers. Six participants received FMT and 2 participants served as controls. No serious adverse effects occurred during 24 weeks of follow-up. At baseline, HIV-infected individuals exhibited microbiota profiles distinct from uninfected donors. During the 8 weeks post-FMT, recipients demonstrated partial engraftment of the donor microbiome (P < 0.05). Recipient microbiota remained significantly distant from donors, unlike that observed following FMT for treatment of C. difficile infection. Systemic inflammatory markers showed no significant change post-FMT. FMT was well-tolerated in ART-treated, HIV-infected individuals. Engraftment was detectable but modest, and appeared to be limited to specific bacterial taxa. Whether antibiotic conditioning can enhance engraftment and the capacity of microbiota to modulate inflammation remains to be investigated.}, }
@article {pmid28540921, year = {2017}, author = {Suez, J and Elinav, E}, title = {The path towards microbiome-based metabolite treatment.}, journal = {Nature microbiology}, volume = {2}, number = {}, pages = {17075}, pmid = {28540921}, issn = {2058-5276}, mesh = {Bacteria/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Microbial Interactions ; Prebiotics/administration &amp; dosage ; Precision Medicine/methods ; Probiotics/*therapeutic use ; }, abstract = {The increasing evidence pointing towards the involvement of the gut microbiome in multiple diseases, as well as its plasticity, renders it a desirable potential therapeutic target. Nevertheless, classical therapies based on the consumption of live probiotic bacteria, or their enrichment by prebiotics, exhibit limited efficacy. Recently, a novel therapeutic approach has been suggested based on metabolites secreted, modulated or degraded by the microbiome. As many of the host-microorganism interactions pertaining to human health are mediated by metabolites, this approach may be able to provide therapeutic efficacy while overcoming caveats of current microbiome-targeting therapies, such as colonization resistance and inter-individual variation in microbial composition. In this Perspective, we will discuss the evidence that supports pursuing the metabolite-based therapeutic approach as well as issues critical for its implementation. In a broader context, we will discuss how recent advances in microbiome research may improve and refine current treatment modalities, and the potential of combining them with metabolite-based interventions as a means of achieving a person-specific, integrated and efficient therapy.}, }
@article {pmid28540475, year = {2017}, author = {Witte, T and Pieper, DH and Heidrich, B}, title = {[Intestinal microbiota in individualized therapies].}, journal = {Der Internist}, volume = {58}, number = {7}, pages = {682-686}, pmid = {28540475}, issn = {1432-1289}, mesh = {Animals ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; }, abstract = {During recent years, the analysis of the human microbiota has been receiving more and more scientific focus. Deep sequencing analysis enables characterization of microbial communities in different environments without the need of culture-based methods. Hereby, information about microbial communities is increasing enormously. Numerous studies in humans and animal models revealed the important role of the microbiome in emergence and natural course of diseases such as autoimmune diseases and metabolic disorders, e. g., the metabolic syndrome. The identification of causalities between the intestinal microbiota composition and function, and diseases in humans and animal models can help to develop individualized therapies targeting the microbiome and its modification. Nowadays, it is established that several factors influence the composition of the microbiota. Diet it is one of the major factors shaping the microbiota and the use of pro- and prebiotica may induce changes in the microbial community. Fecal microbiome transfer is the first approach targeting the intestinal microbiota which is implemented in the clinical routine for patients with therapy-refractory infections with Clostridium difficile. Herewith, the recipient's microbiota can be changed permanently and the patient can be cured from the infection.}, }
@article {pmid28540051, year = {2017}, author = {Chanyi, RM and Craven, L and Harvey, B and Reid, G and Silverman, MJ and Burton, JP}, title = {Faecal microbiota transplantation: Where did it start? What have studies taught us? Where is it going?.}, journal = {SAGE open medicine}, volume = {5}, number = {}, pages = {2050312117708712}, pmid = {28540051}, issn = {2050-3121}, abstract = {The composition and activity of microorganisms in the gut, the microbiome, is emerging as an important factor to consider with regard to the treatment of many diseases. Dysbiosis of the normal community has been implicated in inflammatory bowel disease, Crohn's disease, diabetes and, most notoriously, Clostridium difficile infection. In Canada, the leading treatment strategy for recalcitrant C. difficile infection is to receive faecal material which by nature is filled with microorganisms and their metabolites, from a healthy individual, known as a faecal microbiota transplantation. This influx of bacteria into the gut helps to restore the microbiota to a healthy state, preventing C. difficile from causing further disease. Much of what is known with respect to the microbiota and faecal microbiota transplantation comes from animal studies simulating the human disease. Although these models allow researchers to perform studies that would be difficult in humans, they do not always recapitulate the human microbiome. This makes the translation of these results to humans somewhat questionable. The purpose of this review is to analyse these animal models and discuss the advantages and the disadvantages of them in relation to human translation. By understanding some of the limitation of animal models, we will be better able to design and perform experiments of most relevance to human applications.}, }
@article {pmid28539351, year = {2018}, author = {Zuo, T and Wong, SH and Lam, K and Lui, R and Cheung, K and Tang, W and Ching, JYL and Chan, PKS and Chan, MCW and Wu, JCY and Chan, FKL and Yu, J and Sung, JJY and Ng, SC}, title = {Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome.}, journal = {Gut}, volume = {67}, number = {4}, pages = {634-643}, pmid = {28539351}, issn = {1468-3288}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; *Bacteriophages ; Case-Control Studies ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Vancomycin/*therapeutic use ; }, abstract = {OBJECTIVE: Faecal microbiota transplantation (FMT) is effective for the treatment of recurrent Clostridium difficile infection (CDI). Studies have shown bacterial colonisation after FMT, but data on viral alterations in CDI are scarce. We investigated enteric virome alterations in CDI and the association between viral transfer and clinical outcome in patients with CDI.<br><br>DESIGN: Ultra-deep metagenomic sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on stool samples from 24 subjects with CDI and 20 healthy controls. We longitudinally assessed the virome and bacterial microbiome changes in nine CDI subjects treated with FMT and five treated with vancomycin. Enteric virome alterations were assessed in association with treatment response.<br><br>RESULTS: Subjects with CDI demonstrated a significantly higher abundance of bacteriophage Caudovirales and a lower Caudovirales diversity, richness and evenness compared with healthy household controls. Significant correlations were observed between bacterial families Proteobacteria, Actinobacteria and Caudovirales taxa in CDI. FMT treatment resulted in a significant decrease in the abundance of Caudovirales in CDI. Cure after FMT was observed when donor-derived Caudovirales contigs occupied a larger fraction of the enteric virome in the recipients (p=0.024). In treatment responders, FMT was associated with alterations in the virome and the bacterial microbiome, while vancomycin treatment led to alterations in the bacterial community alone.<br><br>CONCLUSIONS: In a preliminary study, CDI is characterised by enteric virome dysbiosis. Treatment response in FMT was associated with a high colonisation level of donor-derived Caudovirales taxa in the recipient. Caudovirales bacteriophages may play a role in the efficacy of FMT in CDI.<br><br>TRIAL REGISTRATION NUMBER: NCT02570477.}, }
@article {pmid28536285, year = {2017}, author = {Kang, C and Wang, B and Kaliannan, K and Wang, X and Lang, H and Hui, S and Huang, L and Zhang, Y and Zhou, M and Chen, M and Mi, M}, title = {Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet.}, journal = {mBio}, volume = {8}, number = {3}, pages = {}, pmid = {28536285}, issn = {2150-7511}, mesh = {Animals ; Anti-Obesity Agents/*administration &amp; dosage ; Capsaicin/*administration &amp; dosage ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Diet, High-Fat ; Disease Models, Animal ; Dysbiosis/complications ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Inflammation/complications ; Mice ; Obesity/*prevention &amp; control ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI) responsible for the development of obesity. Capsaicin (CAP) is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD) supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA) measurements, and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae, while it caused lower levels of members of the lipopolysaccharide (LPS)-producing family S24_7. Predicted function analysis (PICRUSt) showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB1) by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation.IMPORTANCE Metabolic endotoxemia due to gut microbial dysbiosis is a major contributor to the pathogenesis of chronic low-grade inflammation (CLGI), which primarily mediates the development of obesity. A dietary strategy to reduce endotoxemia appears to be an effective approach for addressing the issue of obesity. Capsaicin (CAP) is the major pungent component in red chili (genus Capsicum). Little is known about the role of gut microbiota in the anti-obesity effect of CAP. High-throughput 16S rRNA gene sequencing revealed that CAP significantly increased butyragenic bacteria and decreased LPS-producing bacteria (e.g., members of the S24-7 family) and LPS biosynthesis. By using antibiotics and microbiota transplantation, we prove that gut microbiota plays a causal role in dietary CAP-induced protective phenotype against high-fat-diet-induced CLGI and obesity. Moreover, CB1 inhibition was partially involved in the beneficial effect of CAP. Together, these data suggest that the gut microbiome is a critical factor for the anti-obesity effects of CAP.}, }
@article {pmid28531908, year = {2017}, author = {Bafeta, A and Yavchitz, A and Riveros, C and Batista, R and Ravaud, P}, title = {Methods and Reporting Studies Assessing Fecal Microbiota Transplantation: A Systematic Review.}, journal = {Annals of internal medicine}, volume = {167}, number = {1}, pages = {34-39}, doi = {10.7326/M16-2810}, pmid = {28531908}, issn = {1539-3704}, mesh = {Clostridioides difficile ; Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/therapy ; *Research Design ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) could be a novel treatment option for several chronic diseases associated with altered gut microbiota.<br><br>PURPOSE: To examine the conduct and reporting of studies assessing FMT.<br><br>DATA SOURCES: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science from inception to 31 January 2017.<br><br>STUDY SELECTION: Two reviewers independently examined titles and abstracts to identify all English-language reports of human clinical studies assessing the safety or efficacy of FMT.<br><br>DATA EXTRACTION: Three reviewers independently assessed study types and characteristics and the reporting of important methodological components of the FMT intervention.<br><br>DATA SYNTHESIS: Most (84%) of the 85 published reports found addressed the use of FMTs for Clostridium difficile infection or inflammatory bowel disease, and most (87%) were non-randomized controlled trials. Important methodological components that were not reported in published studies included the following: eligibility criteria for donors (47%), materials used for collecting stools and the period of collection (96%), methods used for conservation of stools (76%), the amount and type of stools used (for example, fresh or frozen), and duration of stool conservation (67%). Many (58%) did not report an analysis of microbiota composition.<br><br>LIMITATIONS: Lack of universal consensus regarding the most important methodological components of FMT and inability to assess the actual conduct of studies and whether the publication process affected the completeness of reporting.<br><br>CONCLUSION: Key components of FMT interventions, which are necessary to replicate and understand study findings about efficacy and safety, are poorly reported.<br><br>PRIMARY FUNDING SOURCE: No specific funding.}, }
@article {pmid28531905, year = {2017}, author = {Young, VB}, title = {Treatment With Fecal Microbiota Transplantation: The Need for Complete Methodological Reporting for Clinical Trials.}, journal = {Annals of internal medicine}, volume = {167}, number = {1}, pages = {61-62}, pmid = {28531905}, issn = {1539-3704}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; U19 AI116482/AI/NIAID NIH HHS/United States ; }, mesh = {Clinical Trials as Topic/*standards ; *Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Research Design/standards ; }, }
@article {pmid28530702, year = {2017}, author = {Wu, H and Esteve, E and Tremaroli, V and Khan, MT and Caesar, R and Mannerås-Holm, L and Ståhlman, M and Olsson, LM and Serino, M and Planas-Fèlix, M and Xifra, G and Mercader, JM and Torrents, D and Burcelin, R and Ricart, W and Perkins, R and Fernàndez-Real, JM and Bäckhed, F}, title = {Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug.}, journal = {Nature medicine}, volume = {23}, number = {7}, pages = {850-858}, pmid = {28530702}, issn = {1546-170X}, mesh = {Animals ; Bile Acids and Salts/metabolism ; DNA, Bacterial/*analysis ; Diabetes Mellitus, Type 2/*drug therapy/microbiology ; Double-Blind Method ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Germ-Free Life ; Glucose Tolerance Test ; Humans ; Hypoglycemic Agents/*therapeutic use ; In Vitro Techniques ; Male ; Metagenomics ; Metformin/*therapeutic use ; Mice ; Middle Aged ; }, abstract = {Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin-microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla, and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters. Our findings provide support for the notion that altered gut microbiota mediates some of metformin's antidiabetic effects.}, }
@article {pmid28529928, year = {2017}, author = {Ekmekciu, I and von Klitzing, E and Fiebiger, U and Neumann, C and Bacher, P and Scheffold, A and Bereswill, S and Heimesaat, MM}, title = {The Probiotic Compound VSL#3 Modulates Mucosal, Peripheral, and Systemic Immunity Following Murine Broad-Spectrum Antibiotic Treatment.}, journal = {Frontiers in cellular and infection microbiology}, volume = {7}, number = {}, pages = {167}, pmid = {28529928}, issn = {2235-2988}, mesh = {Adaptive Immunity/*immunology ; Animals ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; B-Lymphocytes ; Bacteria/classification/*drug effects/*immunology ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Colon ; Cytokines/metabolism ; Dendritic Cells/immunology ; Drug Combinations ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/*immunology ; Immunity, Innate/*immunology ; Immunohistochemistry ; Intestinal Mucosa/immunology/microbiology ; Intestines/immunology/microbiology ; Lymph Nodes ; Mice ; Mice, Inbred C57BL ; Probiotics/pharmacology/*therapeutic use ; Spleen ; T-Lymphocytes/immunology ; T-Lymphocytes, Regulatory ; }, abstract = {There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. Bulgaricus) in reversing immunological effects of microbiota depletion as compared to reassociation with a complex murine microbiota. To address this, conventional mice were subjected to broad-spectrum antibiotic therapy for 8 weeks and perorally reassociated with either VSL#3 bacteria or a complex murine microbiota. VSL#3 recolonization resulted in restored CD4+ and CD8+ cell numbers in the small and large intestinal lamina propria as well as in B220+ cell numbers in the former, whereas probiotic intervention was not sufficient to reverse the antibiotic induced changes of respective cell populations in the spleen. However, VSL#3 application was as efficient as complex microbiota reassociation to attenuate the frequencies of regulatory T cells, activated dendritic cells and memory/effector T cells in the small intestine, colon, mesenteric lymph nodes, and spleen. Whereas broad-spectrum antibiotic treatment resulted in decreased production of cytokines such as IFN-γ, IL-17, IL-22, and IL-10 by CD4+ cells in respective immunological compartments, VSL#3 recolonization was sufficient to completely recover the expression of the anti-inflammatory cytokine IL-10 without affecting pro-inflammatory mediators. In summary, the probiotic compound VSL#3 has an extensive impact on mucosal, peripheral, and systemic innate as well as adaptive immunity, exerting beneficial anti-inflammatory effects in intestinal as well as systemic compartments. Hence, VSL#3 might be considered a therapeutic immunomodulatory tool following antibiotic therapy.}, }
@article {pmid28529025, year = {2017}, author = {Terveer, EM and van Beurden, YH and Goorhuis, A and Seegers, JFML and Bauer, MP and van Nood, E and Dijkgraaf, MGW and Mulder, CJJ and Vandenbroucke-Grauls, CMJE and Verspaget, HW and Keller, JJ and Kuijper, EJ}, title = {How to: Establish and run a stool bank.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {23}, number = {12}, pages = {924-930}, doi = {10.1016/j.cmi.2017.05.015}, pmid = {28529025}, issn = {1469-0691}, mesh = {Biological Specimen Banks/*organization &amp; administration/standards ; *Fecal Microbiota Transplantation ; *Feces ; Humans ; Netherlands ; }, abstract = {BACKGROUND: Since 2013, several stool banks have been developed following publications reporting on clinical success of 'faecal microbiota transplantation' (FMT) for recurrent Clostridium difficile infections (CDI). However, protocols for donor screening, faecal suspension preparation, and transfer of the faecal suspension differ between countries and institutions. Moreover, no European consensus exists regarding the legislative aspects of the faecal suspension product. Internationally standardized recommendations about the above mentioned aspects have not yet been established.<br><br>OBJECTIVE: In 2015, the Netherlands Donor Feces Bank (NDFB) was founded with the primary aim of providing a standardized product for the treatment of patients with recurrent CDI in the Netherlands. Standard operation procedures for donor recruitment, donor selection, donor screening, and production, storage, and distribution of frozen faecal suspensions for FMT were formulated.<br><br>RESULTS AND DISCUSSION: Our experience summarized in this review addresses current donor recruitment and screening, preparation of the faecal suspension, transfer of the faecal microbiota suspension, and the experiences and follow-up of the patients treated with donor faeces from the NDFB.}, }
@article {pmid28527651, year = {2017}, author = {Teranishi, H and Koga, Y and Nishio, H and Kato, W and Ono, H and Kanno, S and Nakashima, K and Takada, H}, title = {Clinical efficacy of cycling empirical antibiotic therapy for febrile neutropenia in pediatric cancer patients.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {23}, number = {7}, pages = {463-467}, doi = {10.1016/j.jiac.2017.03.020}, pmid = {28527651}, issn = {1437-7780}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/administration &amp; dosage/*therapeutic use ; Bacteremia/complications/drug therapy/epidemiology/microbiology ; Child ; Child, Preschool ; Drug Resistance, Bacterial ; Empirical Research ; Febrile Neutropenia/complications/*drug therapy/*epidemiology/microbiology ; Feces/microbiology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Nasal Cavity/microbiology ; Neoplasms/*complications ; Prospective Studies ; Retrospective Studies ; Treatment Outcome ; Young Adult ; beta-Lactamases ; }, abstract = {BACKGROUND: Febrile neutropenia (FN) is the main treatment-related cause of mortality among children with cancer, as the prolonged use of broad-spectrum antibiotics can lead to antibiotic resistance in these patients. Antibiotic cycling has been reported to limit the emergence of antibiotic-resistant bacteria among adult patients. However, no studies have evaluated pediatric patients with FN.<br><br>METHODS: Between September 2011 and February 2014, 126 pediatric cancer patients were admitted to our center for chemotherapy and/or hematopoietic stem cell transplantation and were included in this study. Retrospective and prospective data collection were performed before and after antibiotic cycling, respectively. Between September 2011 and November 2012 (before antibiotic cycling was implemented), intravenous cefpirome was used as the empirical therapy for FN. Between December 2012 and February 2014 (after antibiotic cycling was implemented), the monthly antibiotic cycling involved intravenous piperacillin-tazobactam (PIPC/TAZ), intravenous meropenem or ciprofloxacin (CPFX), and intravenous cefepime in that order. For children aged &#x2265;13 years, the monthly cycling involved intravenous PIPC/TAZ, and CPFX was administered.<br><br>RESULTS: The detection rates for extended-spectrum &#x3b2;-lactamase producers in blood and stool culture samples decreased significantly after the implementation of antibiotic cycling (0.33/1000 patient-days vs 0/1000 patient-days, p&#xa0;=&#xa0;0.03; 1.00/1000 patient-days vs 0/1000 patient-days, p&#xa0;<&#xa0;0.01; respectively).<br><br>CONCLUSION: Antibiotic cycling was associated with a decreased emergence of multidrug-resistant microbes.}, }
@article {pmid28526488, year = {2017}, author = {Wiest, R and Albillos, A and Trauner, M and Bajaj, JS and Jalan, R}, title = {Targeting the gut-liver axis in liver disease.}, journal = {Journal of hepatology}, volume = {67}, number = {5}, pages = {1084-1103}, doi = {10.1016/j.jhep.2017.05.007}, pmid = {28526488}, issn = {1600-0641}, mesh = {Disease Management ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; *Liver Diseases/microbiology/physiopathology/therapy ; }, abstract = {The gut-liver axis is widely implicated in the pathogenesis of liver diseases, where it is increasingly the focus of clinical research. Recent studies trialling an array of therapeutic and preventative strategies have yielded promising results. Considering these strategies, the armamentarium for targeting the gut-liver axis will continue to expand. Further clinical trials, translated from our current knowledge of the gut-liver axis, promise an exciting future in liver treatment.}, }
@article {pmid28522956, year = {2017}, author = {Bak, SH and Choi, HH and Lee, J and Kim, MH and Lee, YH and Kim, JS and Cho, YS}, title = {Fecal microbiota transplantation for refractory Crohn's disease.}, journal = {Intestinal research}, volume = {15}, number = {2}, pages = {244-248}, pmid = {28522956}, issn = {1598-9100}, abstract = {Approximately one-third of patients with Crohn's disease do not respond to conventional treatments, and some experience significant adverse effects, such as serious infections and lymphoma, and many patients require surgery due to complications. Increasing evidence suggests that specific changes in the composition of gut microbiota, termed as dysbiosis, are a common feature in patients with inflammatory bowel disease (IBD). Dysbiosis can lead to activation of the mucosal immune system, resulting in chronic inflammation and the development of mucosal lesions. Recently, fecal microbiota transplantation, aimed at modifying the composition of gut microbiota to overcome dysbiosis, has become a potential alternative therapeutic option for IBD. Herein, we present a patient with Crohn's colitis in whom biologic therapy failed previously, but clinical remission and endoscopic improvement was achieved after a single fecal microbiota transplantation infusion.}, }
@article {pmid28522941, year = {2017}, author = {Eun, CS}, title = {Is there a potential role of fecal microbiota transplantation in the treatment of inflammatory bowel disease?.}, journal = {Intestinal research}, volume = {15}, number = {2}, pages = {145-146}, pmid = {28522941}, issn = {1598-9100}, }
@article {pmid28517024, year = {2017}, author = {Lanthier, N and Stärkel, P}, title = {Treatment of severe alcoholic hepatitis: past, present and future.}, journal = {European journal of clinical investigation}, volume = {47}, number = {7}, pages = {531-539}, doi = {10.1111/eci.12767}, pmid = {28517024}, issn = {1365-2362}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Alcohol Abstinence/trends ; Antioxidants/therapeutic use ; Apoptosis/physiology ; Bile Acids and Salts/administration &amp; dosage ; Dietary Supplements ; Gastrointestinal Microbiome/physiology ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Hepatitis, Alcoholic/*therapy ; Humans ; Liver Regeneration/physiology ; Liver Transplantation/trends ; Metabolic Syndrome/complications ; Nutritional Support/trends ; Opportunistic Infections/complications/therapy ; Organ Sparing Treatments/trends ; Oxidative Stress/physiology ; Stem Cell Transplantation/trends ; Thiamine/administration &amp; dosage ; Vitamin B Complex/therapeutic use ; }, abstract = {Alcoholic hepatitis (AH) manifests as a clinical syndrome characterized by recent jaundice and liver function deterioration in an actively drinking patient. The principal cause of AH is alcoholic steatohepatitis (ASH) defined histologically by the coexistence of steatosis, hepatocyte ballooning and satellitosis. While nonsevere AH usually responds to alcohol abstinence, severe AH, identified by Maddrey scoring ≥ 32, has a bad prognosis and is traditionally treated by a 28-day course of prednisone therapy. A recent trial, which showed no improvement of long-term survival but significant reduced mortality after 28 days of corticoid therapy compared to placebo, opens a debate on its efficacy. N-acetyl-cysteine supplementation combined with steroid therapy is also able to reduce the 28-day mortality compared to steroid alone. While guidelines recommend high-calorie intake and protein supplementation in decompensated liver diseases, intensive enteral nutrition together with corticoid treatment does not reduce mortality compared to corticoid alone in a recent study with ASH patients. Stimulation of liver regeneration through interleukin-22, granulocyte colony-stimulating factor or farnesoid X receptor agonists, inhibition of apoptosis, early liver transplantation and modulation of gut microbiota through antibiotic or faecal transplantation approaches constitute new therapeutic perspectives that are investigated in current clinical trials. Inhibition of oxidative stress, modulation of gut fungal populations and stimulation of progenitor cell proliferation and pro-regenerative inflammatory pathways constitute prospects for future human trials. For long-term survival, strategies for persistent alcohol abstinence remain the key of success, opening another large research field.}, }
@article {pmid28516109, year = {2017}, author = {Ferm, S and Varadi, N and Fisher, C and Gutkin, E}, title = {Serum-Derived Bovine Immunoglobulin as Novel Adjunct in Complicated Clostridium difficile Colitis Treatment.}, journal = {ACG case reports journal}, volume = {4}, number = {}, pages = {e64}, pmid = {28516109}, issn = {2326-3253}, abstract = {Clostridium difficile infection (CDI) is a well-known complication of antibiotic therapy. It is associated with significant morbidity, mortality, and cost in the hospital setting. The main symptoms include watery diarrhea, abdominal pain, and distension, but CDI can also present as toxic megacolon, bowel perforation with peritonitis, sepsis and renal failure. Therapy includes metronidazole and oral vancomycin, with rectal vancomycin and fecal transplant reserved for more complicated cases. Adjunctive treatments such as probiotics have been tried with mixed results. We present a patient with complicated CDI treated with adjuvant serum-derived bovine immunoglobulin, a novel approach in this context.}, }
@article {pmid28513974, year = {2017}, author = {Alrabaa, S and Jariwala, R and Zeitler, K and Montero, J}, title = {Fecal microbiota transplantation outcomes in immunocompetent and immunocompromised patients: A single-center experience.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {19}, number = {4}, pages = {}, doi = {10.1111/tid.12726}, pmid = {28513974}, issn = {1399-3062}, mesh = {Aged ; Clostridium Infections/microbiology/*surgery ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Immunocompromised Host ; Male ; Middle Aged ; Risk Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is a major infectious disease focus for which fecal microbiota transplantation (FMT) has been used with success in various patient populations.<br><br>METHODS: We conducted a retrospective study of FMT in immunocompetent and immunocompromised patients to review outcomes at our center, with a focus on identifying risk factors for FMT failure in solid organ transplant (SOT) patients. FMT was conducted using universal banked frozen stool via naso-duodenal tube in patients with recurrent CDI of 3 or more episodes per our institutional protocol.<br><br>RESULTS: Thirteen patients were included in the analysis, 6 who were immunocompetent and 7 who were immunocompromised. Of these, 6 patients had a history of SOT and were primarily abdominal organ recipients. All immunocompetent patients experienced success with FMT, while 3 immunocompromised SOT patients experienced failure. Two patients who failed FMT had a second FMT, which was successful in one patient and failed in the second patient. No adverse events were noted with FMT administration. A predictor of FMT failure was antimicrobial exposure pre-FMT.<br><br>CONCLUSIONS: This study highlights the safe use of FMT for recurrent CDI with variable efficacy in immunocompromised patients. Antimicrobial exposure prior to FMT was an identified risk factor for FMT failure. The use of sequential FMT in SOT patients may be considered but ultimately requires further investigation.}, }
@article {pmid28509739, year = {2017}, author = {Gaines, S and Alverdy, JC}, title = {Fecal Micobiota Transplantation to Treat Sepsis of Unclear Etiology.}, journal = {Critical care medicine}, volume = {45}, number = {6}, pages = {1106-1107}, pmid = {28509739}, issn = {1530-0293}, support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; *Enterocolitis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Sepsis ; }, }
@article {pmid28506447, year = {2017}, author = {Grąt, M and Wronka, KM and Lewandowski, Z and Grąt, K and Krasnodębski, M and Stypułkowski, J and Hołówko, W and Masior, &#x141; and Kosińska, I and Wasilewicz, M and Raszeja-Wyszomirska, J and Rejowski, S and Bik, E and Patkowski, W and Krawczyk, M}, title = {Effects of continuous use of probiotics before liver transplantation: A randomized, double-blind, placebo-controlled trial.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {36}, number = {6}, pages = {1530-1539}, doi = {10.1016/j.clnu.2017.04.021}, pmid = {28506447}, issn = {1532-1983}, mesh = {Adult ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Colony Count, Microbial ; Double-Blind Method ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; *Liver Transplantation ; Male ; Middle Aged ; Postoperative Complications/prevention &amp; control ; *Preoperative Care ; Probiotics/*administration &amp; dosage ; Prospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Although there is increasing evidence for the benefits of probiotics in patients with liver diseases, data on the benefits of pre-LT administration of probiotics are lacking. The aim of this study was to evaluate the effects of continuous administration of probiotics before liver transplantation (LT) on pre- and post-transplant patient outcomes.<br><br>METHODS: In this randomized, double-blind, and placebo-controlled trial adult cirrhotic patients listed for LT received a 4-strain probiotic preparation or placebo daily from enrollment until LT. The primary outcome measures were postoperative mortality and infection rates. The secondary outcome measures were 5-day post-transplant aspartate and alanine aminotransferase activities, bilirubin concentration, and international normalized ratio; waiting-list mortality; pre-transplant Model for End-stage Liver Disease score and Child-Turcotte-Pugh class changes; and pre-transplant infections.<br><br>RESULTS: A total of 55 patients were randomized. The 90-day postoperative mortality rates were 0% and 4.3% in the probiotic and placebo groups, respectively (p&#xa0;>&#xa0;0.99). Patients receiving probiotics had significantly reduced 30-day (4.8% versus 34.8%, p&#xa0;=&#xa0;0.02) and 90-day (4.8% versus 47.8%, p&#xa0;=&#xa0;0.002) infection rates, lower post-LT bilirubin concentration (p&#xa0;=&#xa0;0.02), and more rapid decrease of aspartate (p&#xa0;=&#xa0;0.03) and alanine (p&#xa0;=&#xa0;0.03) aminotransferase activities. Probiotics did not have significant effects on other secondary outcome measures.<br><br>CONCLUSIONS: Although continuous administration of probiotics before LT does not appear to affect postoperative mortality, it effectively prevents postoperative infections and improves early biochemical parameters of allograft function. CLINICALTRIALS.<br><br>GOV IDENTIFIER: NCT01735591.}, }
@article {pmid28506317, year = {2017}, author = {Khanna, S and Vazquez-Baeza, Y and González, A and Weiss, S and Schmidt, B and Muñiz-Pedrogo, DA and Rainey, JF and Kammer, P and Nelson, H and Sadowsky, M and Khoruts, A and Farrugia, SL and Knight, R and Pardi, DS and Kashyap, PC}, title = {Changes in microbial ecology after fecal microbiota transplantation for recurrent C. difficile infection affected by underlying inflammatory bowel disease.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {55}, pmid = {28506317}, issn = {2049-2618}, support = {K08 DK100638/DK/NIDDK NIH HHS/United States ; P30 DK084567/DK/NIDDK NIH HHS/United States ; R03 DK111850/DK/NIDDK NIH HHS/United States ; UL1 TR000135/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteria/*classification/genetics ; Clostridioides difficile/physiology ; Clostridium Infections/complications/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*complications/microbiology ; Male ; Middle Aged ; Sequence Analysis, DNA ; Young Adult ; }, abstract = {BACKGROUND: Gut microbiota play a key role in maintaining homeostasis in the human gut. Alterations in the gut microbial ecosystem predispose to Clostridium difficile infection (CDI) and gut inflammatory disorders such as inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor can restore gut microbial diversity and pathogen colonization resistance; consequently, it is now being investigated for its ability to improve inflammatory gut conditions such as IBD. In this study, we investigated changes in gut microbiota following FMT in 38 patients with CDI with or without underlying IBD.<br><br>RESULTS: There was a significant change in gut microbial composition towards the donor microbiota and an overall increase in microbial diversity consistent with previous studies after FMT. FMT was successful in treating CDI using a diverse set of donors, and varying degrees of donor stool engraftment suggesting that donor type and degree of engraftment are not drivers of a successful FMT treatment of CDI. However, patients with underlying IBD experienced an increased number of CDI relapses (during a 24-month follow-up) and a decreased growth of new taxa, as compared to the subjects without IBD. Moreover, the need for IBD therapy did not change following FMT. These results underscore the importance of the existing gut microbial landscape as a decisive factor to successfully treat CDI and potentially for improvement of the underlying pathophysiology in IBD.<br><br>CONCLUSIONS: FMT leads to a significant change in microbial diversity in patients with recurrent CDI and complete resolution of symptoms. Stool donor type (related or unrelated) and degree of engraftment are not the key for successful treatment of CDI by FMT. However, CDI patients with IBD have higher proportion of the original community after FMT and lack of improvement of their IBD symptoms and increased episodes of CDI on long-term follow-up.}, }
@article {pmid28506071, year = {2017}, author = {Gravito-Soares, M and Gravito-Soares, E and Portela, F and Ferreira, M and Sofia, C}, title = {Fecal microbiota transplantation in recurrent Clostridium difficile infection in a patient with concomitant inflammatory bowel disease.}, journal = {Revista espanola de enfermedades digestivas}, volume = {109}, number = {6}, pages = {473-476}, doi = {10.17235/reed.2017.4819/2016}, pmid = {28506071}, issn = {1130-0108}, mesh = {Clostridioides difficile ; Clostridium Infections/*microbiology/*therapy ; Colitis, Ulcerative/microbiology/therapy ; Enterocolitis, Pseudomembranous/*microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Inflammatory Bowel Diseases/*microbiology/*therapy ; Male ; Middle Aged ; Recurrence ; }, abstract = {The use of fecal microbiota transplantation in recurrent Clostridium difficile infection and coexistent inflammatory bowel disease remains unclear. A 61-year-old man with ulcerative pancolitis was diagnosed with a third recurrence of Clostridium difficile infection, previously treated with metronidazole, vancomycin and fidaxomicin. Fecal microbiota transplantation of an unrelated healthy donor was performed by the lower route. After a twelve month follow-up, the patient remains asymptomatic without Clostridium difficile infection relapses or inflammatory bowel disease flare-ups. Fecal microbiota transplantation is relatively simple to perform, well-tolerated, safe and effective in recurrent Clostridium difficile infection with ulcerative pancolitis, as an alternative in case of antibiotic therapy failure.}, }
@article {pmid28503135, year = {2017}, author = {Li, Q and Han, Y and Dy, ABC and Hagerman, RJ}, title = {The Gut Microbiota and Autism Spectrum Disorders.}, journal = {Frontiers in cellular neuroscience}, volume = {11}, number = {}, pages = {120}, pmid = {28503135}, issn = {1662-5102}, abstract = {Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies have shown alterations in the composition of the fecal flora and metabolic products of the gut microbiome in patients with ASD. The gut microbiota influences brain development and behaviors through the neuroendocrine, neuroimmune and autonomic nervous systems. In addition, an abnormal gut microbiota is associated with several diseases, such as inflammatory bowel disease (IBD), ASD and mood disorders. Here, we review the bidirectional interactions between the central nervous system and the gastrointestinal tract (brain-gut axis) and the role of the gut microbiota in the central nervous system (CNS) and ASD. Microbiome-mediated therapies might be a safe and effective treatment for ASD.}, }
@article {pmid28502839, year = {2017}, author = {Ianiro, G and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year cohort study: authors' reply.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {23}, number = {11}, pages = {891}, doi = {10.1016/j.cmi.2017.05.005}, pmid = {28502839}, issn = {1469-0691}, mesh = {Clostridioides difficile ; *Clostridium Infections ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Recurrence ; }, }
@article {pmid28501333, year = {2017}, author = {Gundacker, ND and Tamhane, A and Walker, JB and Morrow, CD and Rodriguez, JM}, title = {Comparative effectiveness of faecal microbiota transplant by route of administration.}, journal = {The Journal of hospital infection}, volume = {96}, number = {4}, pages = {349-352}, doi = {10.1016/j.jhin.2017.05.004}, pmid = {28501333}, issn = {1532-2939}, support = {P30 CA013148/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome ; }, abstract = {The optimal route of delivery for faecal microbiota transplant (FMT) is unknown. This observational single-centre study analysed the two-week cure rates for all patients who received FMT from 2013 to 2016 according to route of delivery. Overall, nasogastric delivery of FMT was less effective than lower endoscopic delivery. When patients were stratified by illness severity, nasogastric delivery achieved similar cure rates in healthier individuals, whereas lower endoscopic delivery was preferred for relatively ill individuals. Nasogastric delivery may be less effective than lower endoscopic delivery; however, when taking the cost, preparation and potential risk into account, this difference may not be clinically significant for patients with mild disease.}, }
@article {pmid28498996, year = {2017}, author = {Lee, YJ and Arguello, ES and Jenq, RR and Littmann, E and Kim, GJ and Miller, LC and Ling, L and Figueroa, C and Robilotti, E and Perales, MA and Barker, JN and Giralt, S and van den Brink, MRM and Pamer, EG and Taur, Y}, title = {Protective Factors in the Intestinal Microbiome Against Clostridium difficile Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation.}, journal = {The Journal of infectious diseases}, volume = {215}, number = {7}, pages = {1117-1123}, pmid = {28498996}, issn = {1537-6613}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; K23 AI095398/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Bacteroidetes/classification/isolation &amp; purification ; Clostridiales/classification/isolation &amp; purification ; Clostridioides difficile ; Clostridium Infections/*microbiology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Protective Factors ; RNA, Ribosomal, 16S/genetics ; Transplantation, Homologous ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is a frequent complication in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), who receive intensive treatments that significantly disrupt the intestinal microbiota. In this study, we examined the microbiota composition of allo-HSCT recipients to identify bacterial colonizers that confer protection against CDI after engraftment.<br><br>METHODS: Feces collected from adult recipients allo-HSCT at engraftment were analyzed; 16S ribosomal RNA genes were sequenced and analyzed from each sample. Bacterial taxa with protective effects against development of CDI were identified by means of linear discriminant analysis effect size analysis and then further assessed with clinical predictors of CDI using survival analysis.<br><br>RESULTS: A total of 234 allo-HSCT recipients were studied; postengraftment CDI developed in 53 (22.6%). Within the composition of the microbiota, the presence of 3 distinct bacterial taxa was correlated with protection against CDI: Bacteroidetes, Lachnospiraceae, and Ruminococcaceae. Colonization with these groups at engraftment was associated with a 60% lower risk of CDI, independent of clinical factors.<br><br>CONCLUSIONS: Colonization with these 3 bacterial groups is associated with a lower risk of CDI. These groups have been shown to be vital components of the intestinal microbiota. Targeted efforts to maintain them may help minimize the risk of CDI in this at-risk population.}, }
@article {pmid28495755, year = {2017}, author = {Shi, J and Wang, Y and He, J and Li, P and Jin, R and Wang, K and Xu, X and Hao, J and Zhang, Y and Liu, H and Chen, X and Wu, H and Ge, Q}, title = {Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {31}, number = {8}, pages = {3695-3709}, doi = {10.1096/fj.201700034R}, pmid = {28495755}, issn = {1530-6860}, mesh = {Animals ; Bacteria/*classification/genetics ; Colon/*pathology ; Dysbiosis ; Epithelial Cells/physiology ; Feces/chemistry ; Female ; Homeostasis ; Immunoglobulin A/chemistry ; Intestinal Mucosa/*microbiology/pathology ; Mice ; Mice, Inbred C57BL ; Microbiota/*physiology ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Random Allocation ; *Weightlessness Simulation ; }, abstract = {Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses. As a result, increased susceptibility to dextran sulfate sodium-induced epithelial injury was observed in HU mice. Cohousing of Ctrl mice with HU mice resulted in HU-like epithelial changes in Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these epithelial changes in HU mice. Results indicate that HU changes intestinal microbiota, which leads to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. We further demonstrate that alteration in gastrointestinal motility may contribute to HU-associated dysbiosis. These animal results emphasize the necessity of evaluating astronauts' intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model.}, }
@article {pmid28493000, year = {2017}, author = {Buonfrate, D and Paradies, P and Iarussi, F and Formenti, F and Perandin, F and Otranto, D and Bisoffi, Z}, title = {Serological and molecular tests for the diagnosis of Strongyloides stercoralis infection in dogs.}, journal = {Parasitology research}, volume = {116}, number = {7}, pages = {2027-2029}, pmid = {28493000}, issn = {1432-1955}, mesh = {Animals ; Dog Diseases/diagnosis/*parasitology ; Dogs ; Enzyme-Linked Immunosorbent Assay/methods/veterinary ; Feces/parasitology ; Italy ; Molecular Diagnostic Techniques/veterinary ; Real-Time Polymerase Chain Reaction/veterinary ; *Strongyloides stercoralis/genetics ; Strongyloidiasis/diagnosis/parasitology/*veterinary ; }, abstract = {Strongyloides stercoralis can cause severe infection both in humans and dogs. Coproparasitological examination has low sensitivity for the diagnosis of this parasite; hence, different diagnostic techniques have been implemented. However, serology and molecular methods have been assessed almost exclusively in humans. In this study, two serologic assays and a real-time PCR (RT-PCR), routinely used for the diagnosis of strongyloidiasis in humans, have been tested for the diagnosis in dogs. Five dogs living in the same kennel in Bari, southern Italy, were diagnosed with S. stercoralis infection by detection of larvae in fecal samples processed by the Baermann method. Serum, fecal, and tissue (lungs, scraping of intestinal tract) samples from the same dogs were tested with two serologic assays (commercial ELISA, in-house IFAT) and with an in-house RT-PCR, routinely used for diagnosis in humans. IFAT was positive in all serum samples, ELISA in 3/7 (42.8%) samples. RT-PCR was positive in all pre-treatment fecal samples, in all fecal debris, and in intestinal scraping (three samples from the same deceased dog). The results suggest that IFAT and RT-PCR techniques routinely used for S. stercoralis diagnosis in humans could be useful for the diagnosis of the infection in dogs.}, }
@article {pmid28491142, year = {2017}, author = {van Beurden, YH and Nieuwdorp, M and van de Berg, PJEJ and Mulder, CJJ and Goorhuis, A}, title = {Current challenges in the treatment of severe Clostridium difficile infection: early treatment potential of fecal microbiota transplantation.}, journal = {Therapeutic advances in gastroenterology}, volume = {10}, number = {4}, pages = {373-381}, pmid = {28491142}, issn = {1756-283X}, abstract = {Fecal microbiota transplantation (FMT) is a very effective treatment for recurrent Clostridium difficile infection (CDI). Less is known about the application of FMT as a curative treatment of severe or complicated CDI. In this review, we present and discuss evidence supporting the curative use of FMT in severe or complicated CDI. We performed a literature search in PubMed and Embase for studies on the curative use of FMT in severe or complicated CDI. In addition, we describe a patient with severe CDI not responding to initial antibiotic treatment, who was successfully treated with curative FMT. We found 23 reports (12 case reports; 11 case series) about FMT as treatment for severe or complicated CDI. The patients described all had severe or complicated CDI, did not respond to conventional CDI antibiotic treatment and received FMT as last resort treatment. Patients were treated with (sequential) FMT, whether or not followed by additional antibiotic treatment for CDI. FMT, with or without additional antibiotic CDI treatment, appears to be a promising curative treatment option in patients with severe and complicated CDI, or only complicated CDI, who do not respond sufficiently to conventional antibiotic treatment. Treatment with FMT should be considered in these patients before proceeding to emergency bowel surgery.}, }
@article {pmid28486648, year = {2017}, author = {Paramsothy, S and Paramsothy, R and Rubin, DT and Kamm, MA and Kaakoush, NO and Mitchell, HM and Castaño-Rodríguez, N}, title = {Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {11}, number = {10}, pages = {1180-1199}, doi = {10.1093/ecco-jcc/jjx063}, pmid = {28486648}, issn = {1876-4479}, mesh = {Colitis, Ulcerative/therapy ; Crohn Disease/therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation [FMT] has been investigated as a potential treatment for inflammatory bowel disease [IBD]. We thus performed a systematic review and meta-analysis assessing the effectiveness and safety of FMT in IBD.<br><br>METHODS: A systematic review was conducted until January 2017. Studies were excluded if patients had co-infection or data were pooled across disease subtypes (ulcerative colitis [UC], Crohn's disease [CD], pouchitis). Clinical remission was established as the primary outcome. Pooled effect sizes and 95% confidence intervals were obtained using the random effects model.<br><br>RESULTS: In all, 53 studies were included [41 in UC, 11 in CD, 4 in pouchitis]. Overall, 36% [201/555] of UC, 50.5% [42/83] of CD, and 21.5% [5/23] of pouchitis patients achieved clinical remission. Among cohort studies, the pooled proportion achieving clinical remission was 33% (95% confidence interval [CI] = 23%-43%] for UC and 52% [95% CI = 31%-72%] for CD, both with moderate risk of heterogeneity. For four RCTs in UC, significant benefit in clinical remission (pooled odds ratios [[P-OR] = 2.89, 95% CI = 1.36-6.13, p = 0.006) with moderate heterogeneity [Cochran's Q, p = 0.188; I2 = 37%] was noted. Sub-analyses suggest remission in UC improved with increased number of FMT infusions and lower gastrointestinal tract administration. Most adverse events were transient gastrointestinal complaints. Microbiota analysis was performed in 24 studies, with many identifying increased diversity and a shift in recipient microbiota profile towards the donor post-FMT.<br><br>CONCLUSIONS: FMT appears effective in UC remission induction, but long-term durability and safety remain unclear. Additional well-designed controlled studies of FMT in IBD are needed, especially in CD and pouchitis.}, }
@article {pmid28484247, year = {2017}, author = {Zhou, D and Pan, Q and Shen, F and Cao, HX and Ding, WJ and Chen, YW and Fan, JG}, title = {Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {1529}, pmid = {28484247}, issn = {2045-2322}, mesh = {Adipose Tissue/pathology ; Animals ; Body Weight ; Butyric Acid/metabolism ; Cecum/metabolism ; Diet, High-Fat ; Endotoxemia/pathology ; Epididymis/pathology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Inflammation/blood/pathology ; Insulin Resistance ; Intestine, Small/pathology ; Liver/immunology/injuries/metabolism/pathology ; Male ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/blood/*microbiology/*therapy ; Obesity/microbiology/therapy ; Tight Junctions/metabolism ; Transaminases/blood ; }, abstract = {Non-alcoholic steatohepatitis (NASH) is an epidemic metabolic disease with limited therapeutic strategies. Cumulative data support the pivotal role of gut microbiota in NASH. Here, we investigated the hypothesis regarding whether fecal microbiota transplantation (FMT) is effective in attenuating high-fat diet (HFD)-induced steatohepatitis in mice. Mice were randomized into control, HFD and HFD + FMT groups. After an 8-week HFD, FMT treatment was initiated and carried out for 8 weeks. The gut microbiota structure, butyrate concentrations of the cecal content, liver pathology and intrahepatic lipid and cytokines were examined. Our results showed that after FMT, the gut microbiota disturbance was corrected in HFD-fed mice with elevated abundances of the beneficial bacteria Christensenellaceae and Lactobacillus. FMT also increased butyrate concentrations of the cecal content and the intestinal tight junction protein ZO-1, resulting in relief of endotoxima in HFD-fed mice. Steatohepatitis was alleviated after FMT, as indicated by a significant decrease in intrahepatic lipid accumulation (reduced Oli-red staining, decreased intrahepatic triglyceride and cholesterol), intrahepatic pro-inflammatory cytokines, and the NAS score. Accordingly, intrahepatic IFN-γ and IL-17 were decreased, but Foxp3, IL-4 and IL-22 were increased after FMT intervention. These data indicate that FMT attenuated HFD-induced steatohepatitis in mice via a beneficial effect on the gut microbiota.}, }
@article {pmid28473000, year = {2017}, author = {Lee, STM and Kahn, SA and Delmont, TO and Shaiber, A and Esen, &#xd6;C and Hubert, NA and Morrison, HG and Antonopoulos, DA and Rubin, DT and Eren, AM}, title = {Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {50}, pmid = {28473000}, issn = {2049-2618}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; T32 EB009412/EB/NIBIB NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification/*growth &amp; development ; Clostridium Infections/microbiology/*therapy ; DNA, Bacterial/genetics ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Living Donors ; Male ; Metagenomics/*methods ; Phylogeny ; Sequence Analysis, DNA/methods ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection and shows promise for treating other medical conditions associated with intestinal dysbioses. However, we lack a sufficient understanding of which microbial populations successfully colonize the recipient gut, and the widely used approaches to study the microbial ecology of FMT experiments fail to provide enough resolution to identify populations that are likely responsible for FMT-derived benefits.<br><br>METHODS: We used shotgun metagenomics together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from fecal samples of a single FMT donor. We then used metagenomic mapping to track the occurrence and distribution patterns of donor MAGs in two FMT recipients.<br><br>RESULTS: Our analyses revealed that 22% of the 92 highly complete bacterial MAGs that we identified from the donor successfully colonized and remained abundant in two recipients for at least 8&#xa0;weeks. Most MAGs with a high colonization rate belonged to the order Bacteroidales. The vast majority of those that lacked evidence of colonization belonged to the order Clostridiales, and colonization success was negatively correlated with the number of genes related to sporulation. Our analysis of 151 publicly available gut metagenomes showed that the donor MAGs that colonized both recipients were prevalent, and the ones that colonized neither were rare across the participants of the Human Microbiome Project. Although our dataset showed a link between taxonomy and the colonization ability of a given MAG, we also identified MAGs that belong to the same taxon with different colonization properties, highlighting the importance of an appropriate level of resolution to explore the functional basis of colonization and to identify targets for cultivation, hypothesis generation, and testing in model systems.<br><br>CONCLUSIONS: The analytical strategy adopted in our study can provide genomic insights into bacterial populations that may be critical to the efficacy of FMT due to their success in gut colonization and metabolic properties, and guide cultivation efforts to investigate mechanistic underpinnings of this procedure beyond associations.}, }
@article {pmid28471624, year = {2016}, author = {Pitashny, M}, title = {The Giving Microbiome: Share the Health.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {18}, number = {10}, pages = {623-624}, pmid = {28471624}, issn = {1565-1088}, mesh = {Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Microbiota/*physiology ; }, }
@article {pmid28471618, year = {2016}, author = {Cohen, NA and Livovsky, DM and Yaakobovitch, S and Ben Yehoyada, M and Ben Ami, R and Adler, A and Guzner-Gur, H and Goldin, E and Santo, ME and Halpern, Z and Paz, K and Maharshak, N}, title = {A Retrospective Comparison of Fecal Microbial Transplantation Methods for Recurrent Clostridium Difficile Infection.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {18}, number = {10}, pages = {594-599}, pmid = {28471618}, issn = {1565-1088}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/mortality/*therapy ; Donor Selection ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Follow-Up Studies ; Gastrointestinal Tract/*metabolism ; Humans ; Israel ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Antibiotic treatment of Clostridium difficile infection (CDI) has a high failure rate. Fecal microbiota transplantation (FMT) has proven very effective in treating these recurrences.<br><br>OBJECTIVES: To determine which method of fecal microbiota transplantation (upper or lower gastrointestinal) and which type of donor (a relative or unrelated) is superior.<br><br>METHODS: This is a retrospective analysis of treatment protocols and outcomes in 22 patients with refractory or recurrent CDI who underwent FMT at two Israeli facilities. Each center used a different donor type, stool preparation and method of delivery. The Tel Aviv Sourasky Medical Center used unrelated fecal donors and frozen stool samples and delivered them primarily (92%) via the lower gastrointestinal (GI) tract. Shaare Zedek Medical Center used fresh donor stool of relatives and delivered them primarily (90%) via the upper GI tract.<br><br>RESULTS: FMT had an overall 2 month cure rate of 89%. Patients treated with FMT that was executed through the lower GI tract recovered faster from the infection (1.6 &#xb1; 1.08 vs. 2.4 &#xb1; 1 days for the upper tract, P = 0.03). The results also showed that patients who received lower GI tract FMTs were more likely to be cured of CDI (100% vs. 75% for upper tract FMTs, P = 0.16). Five patients (22%) died of CDI/FMT-unrelated causes and two (10%) died of CDI/FMT-related causes during the study period.<br><br>CONCLUSIONS: Lower GI tract FMT is a safe and effective treatment for refractory and recurrent CDI, and yields quicker results than upper GI tract FMT.}, }
@article {pmid28470023, year = {2017}, author = {Stalenhoef, JE and Terveer, EM and Knetsch, CW and Van't Hof, PJ and Vlasveld, IN and Keller, JJ and Visser, LG and Kuijper, EJ}, title = {Fecal Microbiota Transfer for Multidrug-Resistant Gram-Negatives: A Clinical Success Combined With Microbiological Failure.}, journal = {Open forum infectious diseases}, volume = {4}, number = {2}, pages = {ofx047}, pmid = {28470023}, issn = {2328-8957}, abstract = {Combined fecal microbiota transfer and antibiotic treatment prevented recurrences of urinary tract infections with multidrug-resistant (MDR) Pseudomonas aeruginosa, but it failed to eradicate intestinal colonization with MDR Escherichia coli. Based on microbiota analysis, failure was not associated with distinct diminished microbiota diversity.}, }
@article {pmid28469619, year = {2017}, author = {Ekmekciu, I and von Klitzing, E and Fiebiger, U and Escher, U and Neumann, C and Bacher, P and Scheffold, A and Kühl, AA and Bereswill, S and Heimesaat, MM}, title = {Immune Responses to Broad-Spectrum Antibiotic Treatment and Fecal Microbiota Transplantation in Mice.}, journal = {Frontiers in immunology}, volume = {8}, number = {}, pages = {397}, pmid = {28469619}, issn = {1664-3224}, abstract = {Compelling evidence demonstrates the pivotal role of the commensal intestinal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. Aim of this study was to investigate the impact of antibiotics induced depletion and subsequent restoration of the intestinal microbiota composition on the murine mucosal and systemic immunity. To address this, conventional C57BL/6j mice were subjected to broad-spectrum antibiotic treatment for 8 weeks. Restoration of the intestinal microbiota by peroral fecal microbiota transplantation (FMT) led to reestablishment of small intestinal CD4[+], CD8[+], and B220[+] as well as of colonic CD4[+] cell numbers as early as 7 days post-FMT. However, at d28 following FMT, colonic CD4[+] and B220[+] cell numbers were comparable to those in secondary abiotic (ABx) mice. Remarkably, CD8[+] cell numbers were reduced in the colon upon antibiotic treatment, and FMT was not sufficient to restore this immune cell subset. Furthermore, absence of gut microbial stimuli resulted in decreased percentages of memory/effector T cells, regulatory T cells, and activated dendritic cells in the small intestine, colon, mesenteric lymph nodes (MLN), and spleen. Concurrent antibiotic treatment caused decreased cytokine production (IFN-γ, IL-17, IL-22, and IL-10) of CD4[+] cells in respective compartments. These effects were, however, completely restored upon FMT. In summary, broad-spectrum antibiotic treatment resulted in profound local (i.e., small and large intestinal), peripheral (i.e., MLN), and systemic (i.e., splenic) changes in the immune cell repertoire that could, at least in part, be restored upon FMT. Further studies need to unravel the distinct molecular mechanisms underlying microbiota-driven changes in immune homeostasis subsequently providing novel therapeutic or even preventive approaches in human immunopathologies.}, }
@article {pmid28469156, year = {2017}, author = {Xu, KY and Xia, GH and Lu, JQ and Chen, MX and Zhen, X and Wang, S and You, C and Nie, J and Zhou, HW and Yin, J}, title = {Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine-N-oxide in chronic kidney disease patients.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {1445}, pmid = {28469156}, issn = {2045-2322}, mesh = {Adult ; Aged ; Animals ; Betaine/metabolism ; Carnitine/metabolism ; Case-Control Studies ; Choline/metabolism ; Clostridiaceae/classification/genetics/*metabolism ; Dysbiosis/*metabolism/microbiology/pathology ; Fecal Microbiota Transplantation ; Female ; Gammaproteobacteria/classification/genetics/*metabolism ; Gastrointestinal Microbiome/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Kidney Function Tests ; Male ; Methylamines/*blood ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Renal Insufficiency, Chronic/*metabolism/microbiology/pathology ; }, abstract = {Chronic kidney disease (CKD) patients have an increased risk of cardiovascular diseases (CVDs). The present study aimed to investigate the gut microbiota and blood trimethylamine-N-oxide concentration (TMAO) in Chinese CKD patients and explore the underlying explanations through the animal experiment. The median plasma TMAO level was 30.33 μmol/L in the CKD patients, which was significantly higher than the 2.08 μmol/L concentration measured in the healthy controls. Next-generation sequence revealed obvious dysbiosis of the gut microbiome in CKD patients, with reduced bacterial diversity and biased community constitutions. CKD patients had higher percentages of opportunistic pathogens from gamma-Proteobacteria and reduced percentages of beneficial microbes, such as Roseburia, Coprococcus, and Ruminococcaceae. The PICRUSt analysis demonstrated that eight genes involved in choline, betaine, L-carnitine and trimethylamine (TMA) metabolism were changed in the CKD patients. Moreover, we transferred faecal samples from CKD patients and healthy controls into antibiotic-treated C57BL/6 mice and found that the mice that received gut microbes from the CKD patients had significantly higher plasma TMAO levels and different composition of gut microbiota than did the comparative mouse group. Our present study demonstrated that CKD patients had increased plasma TMAO levels due to contributions from both impaired renal functions and dysbiosis of the gut microbiota.}, }
@article {pmid28465629, year = {2017}, author = {Ierardi, E and Giorgio, F and Iannone, A and Losurdo, G and Principi, M and Barone, M and Pisani, A and Di Leo, A}, title = {Noninvasive molecular analysis of Helicobacter pylori: Is it time for tailored first-line therapy?.}, journal = {World journal of gastroenterology}, volume = {23}, number = {14}, pages = {2453-2458}, pmid = {28465629}, issn = {2219-2840}, mesh = {Anti-Bacterial Agents/*therapeutic use ; *Bacteriological Techniques ; DNA, Bacterial/genetics ; Drug Resistance, Bacterial ; Feces/microbiology ; Genotype ; Helicobacter Infections/diagnosis/*drug therapy/microbiology ; Helicobacter pylori/*drug effects/genetics ; Humans ; Microbial Sensitivity Tests ; *Molecular Diagnostic Techniques ; Mutation ; *Precision Medicine ; Predictive Value of Tests ; }, abstract = {The main problem of Helicobacter pylori (H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction (PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin susceptibility have shown an overall high sensitivity and specificity when compared with culture or PCR on gastric biopsies. On these bases, two commercial tests are now available although they have shown some controversial findings. A novel PCR method showed a full concordance between tissue and stool results in a preliminary experience. In conclusion, despite poor validation, there is increasing evidence of a potential availability of noninvasive investigations able to detect H. pylori resistances to antibiotics. These kinds of analysis are currently at a very early phase of development and caution should be paid about their clinical application. Only further studies aimed to evaluate their sensitivity and specificity will afford novel data for solid considerations. Nevertheless, noninvasive molecular tests may improve patient compliance, time/cost of infection management and therapeutic outcome. Moreover, the potential risk of a future increase of resistance to quadruple regimens as a consequence of their use on large scale and incomplete patient adherence could be avoided.}, }
@article {pmid28465369, year = {2017}, author = {}, title = {Statins: time to rationalise LFTs?.}, journal = {Drug and therapeutics bulletin}, volume = {55}, number = {5}, pages = {50}, doi = {10.1136/dtb.2017.5.0471}, pmid = {28465369}, issn = {1755-5248}, mesh = {Chemical and Drug Induced Liver Injury/*diagnosis/epidemiology/etiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration &amp; dosage/*adverse effects ; Liver Function Tests/*methods ; }, abstract = {Statins: time to rationalise LFTs? ● Limited evidence for low-cost devices to improve adherence ● MHRA safety alert: hyoscine butylbromide (Buscopan) injection ● Faecal microbiota transplantation for ulcerative colitis ● Magnesium for nocturnal leg cramps ● NSAIDs and risk of out-of-hospital cardiac arrest ● Off-label antidepressant prescribing.}, }
@article {pmid28465368, year = {2017}, author = {}, title = {Faecal microbiota transplantation for ulcerative colitis.}, journal = {Drug and therapeutics bulletin}, volume = {55}, number = {5}, pages = {51-52}, doi = {10.1136/dtb.2017.5.0474}, pmid = {28465368}, issn = {1755-5248}, }
@article {pmid28461230, year = {2017}, author = {Mahieu, R and Cassisa, V and Hilliquin, D and Coron, N and Pailhoriès, H and Kempf, M and Joly-Guillou, ML and Eveillard, M}, title = {Impact of faecal microbiota transplantation on mouse digestive colonization with two extensively resistant bacteria.}, journal = {The Journal of infection}, volume = {75}, number = {1}, pages = {75-77}, doi = {10.1016/j.jinf.2017.04.008}, pmid = {28461230}, issn = {1532-2742}, mesh = {Animals ; Anti-Bacterial Agents ; *Enterococcus faecium ; *Fecal Microbiota Transplantation ; Feces ; Gram-Positive Bacterial Infections ; Mice ; }, }
@article {pmid28457354, year = {2017}, author = {Curry, SR}, title = {Clostridium difficile.}, journal = {Clinics in laboratory medicine}, volume = {37}, number = {2}, pages = {341-369}, doi = {10.1016/j.cll.2017.01.007}, pmid = {28457354}, issn = {1557-9832}, support = {K23 AI125607/AI/NIAID NIH HHS/United States ; }, mesh = {Clostridioides difficile/*pathogenicity ; *Clostridium Infections/diagnosis/epidemiology/therapy ; False Positive Reactions ; Fecal Microbiota Transplantation ; *Hospitalization ; Humans ; *Immunocompromised Host ; Microbiota ; }, abstract = {Clostridium difficile infections (CDIs) have emerged as one of the principal threats to the health of hospitalized and immunocompromised patients. The importance of C difficile colonization is increasingly recognized not only as a source for false-positive clinical testing but also as a source of new infections within hospitals and other health care environments. In the last five years, several new treatment strategies that capitalize on the increasing understanding of the altered microbiome and host defenses in patients with CDI have completed clinical trials, including fecal microbiota transplantation. This article highlights the changing epidemiology, laboratory diagnostics, pathogenesis, and treatment of CDI.}, }
@article {pmid28451916, year = {2017}, author = {Meighani, A and Hart, BR and Bourgi, K and Miller, N and John, A and Ramesh, M}, title = {Outcomes of Fecal Microbiota Transplantation for Clostridium difficile Infection in Patients with Inflammatory Bowel Disease.}, journal = {Digestive diseases and sciences}, volume = {62}, number = {10}, pages = {2870-2875}, pmid = {28451916}, issn = {1573-2568}, mesh = {Adult ; Aged ; Clostridioides difficile/immunology/*pathogenicity ; Enterocolitis, Pseudomembranous/diagnosis/immunology/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Humans ; Immunocompromised Host ; Inflammatory Bowel Diseases/*complications/diagnosis/drug therapy/immunology ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) has recently been shown to be a promising therapy for recurrent and refractory Clostridium difficile infections (CDI) despite lack of protocol standardization. Patients with inflammatory bowel disease (IBD) present a particular challenge to CDI therapy as they are reported to have worse clinical outcomes, including higher colectomy rates and increased mortality. We aimed to assess the outcomes of FMT for recurrent CDI in patients with IBD at our healthcare system.<br><br>METHODS: We constructed a retrospective cohort of all patients who underwent FMT at our healthcare system between December 2012 and May 2014. Patients with concurrent IBD were identified. We evaluated the differences in demographic and clinical characteristics, along with the outcomes to FMT between patients with IBD as compared to the general population.<br><br>RESULTS: Over the study period, 201 patients underwent FMT of which 20 patients had concurrent IBD. Patients with IBD were younger but did not differ from the general population in terms of CDI risk factors or disease severity. The response to FMT and rate of CDI relapse in the IBD group were not statistically different compared to the rest of the cohort. The overall response rate in the IBD population was 75% at 12&#xa0;weeks. Of the patients who failed FMT 4 of 5 patients had active or untreated IBD.<br><br>CONCLUSION: Fecal microbiota transplantation provides a good alternative treatment option with high success rates for recurrent or refractory Clostridium difficile infection in patients with well-controlled IBD who fail standard antimicrobial therapy.}, }
@article {pmid28449424, year = {2017}, author = {Bang, BW and Park, JS and Kim, HK and Shin, YW and Kwon, KS and Kwon, HY and Baek, JH and Lee, JS}, title = {Fecal Microbiota Transplantation for Refractory and Recurrent Clostridium difficile Infection: A Case Series of Nine Patients.}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {69}, number = {4}, pages = {226-231}, doi = {10.4166/kjg.2017.69.4.226}, pmid = {28449424}, issn = {2233-6869}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/diagnosis/drug therapy/*therapy ; Colonoscopy ; Duodenoscopy ; Enterocolitis, Pseudomembranous/diagnosis/drug therapy/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Pneumonia, Aspiration/etiology ; Recurrence ; }, abstract = {BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) is a highly effective therapy for refractory and recurrent Clostridium difficile infection (CDI). Despite its excellent efficacy and recent widespread use, FMT has not been widely used in South Korea thus far. We describe our experience with FMT to treat refractory/recurrent CDI.<br><br>METHODS: We conducted a chart review of patients who underwent FMT for refractory/recurrent CDI at Inha University Hospital, between March 2014 and June 2016. The demographic information, treatment data, and adverse events were reviewed. FMT was administered via colonoscopy and/or duodenoscopy. All stool donors were rigorously screened to prevent infectious disease transmission.<br><br>RESULTS: FMT was performed in nine patients with refractory/recurrent CDI. All patients were dramatically cured. Bowel movement was normalized within one week after FMT. There were no procedure-related adverse events, except aspiration pneumonia in one patient. During the follow-up period (mean 11.4 months), recurrence of CDI was observed in one patient at one month after FMT due to antibiotics.<br><br>CONCLUSIONS: FMT is a safe, well-tolerated and highly effective treatment for refractory/recurrent CDI. Although there are many barriers to using FMT, we expect that FMT will be widely used to treat refractory/recurrent CDI in South Korea.}, }
@article {pmid28446519, year = {2017}, author = {Zhu, A and Chen, J and Wu, P and Luo, M and Zeng, Y and Liu, Y and Zheng, H and Zhang, L and Chen, Z and Sun, Q and Li, W and Duan, Y and Su, D and Xiao, Z and Duan, Z and Zheng, S and Bai, L and Zhang, X and Ju, Z and Li, Y and Hu, R and Pandol, SJ and Han, YP}, title = {Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing Endotoxemia.}, journal = {Diabetes}, volume = {66}, number = {8}, pages = {2137-2143}, pmid = {28446519}, issn = {1939-327X}, support = {P01 CA163200/CA/NCI NIH HHS/United States ; P01 DK098108/DK/NIDDK NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Cation Exchange Resins/*administration &amp; dosage ; Diet, High-Fat/adverse effects ; Dysbiosis/drug therapy/microbiology ; Endotoxemia/*drug therapy/microbiology ; Endotoxins/blood ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*drug effects ; Insulin Resistance ; Male ; Metabolic Diseases/microbiology/*therapy ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/*drug therapy/microbiology ; Obesity/*drug therapy/microbiology ; Polystyrenes/*administration &amp; dosage ; Symbiosis/drug effects ; Treatment Outcome ; }, abstract = {A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic fatty liver disease, and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low-cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine, but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to 1) reduced plasma endotoxin levels, 2) resolved systemic inflammation and hepatic steatohepatitis, and 3) improved insulin sensitivity. Gut dysbiosis, characterized as an increase of the phylum Firmicutes and a decrease of Bacteroidetes and Akkermansia muciniphila, was fully corrected by cholestyramine, indicating that the negatively charged components in the gut are critical for the dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine-treated animals, was sufficient to antagonize the metabolic disorders of the recipient mice. These results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis.}, }
@article {pmid28445487, year = {2017}, author = {Katiraei, S and Hoving, LR and van Beek, L and Mohamedhoesein, S and Carlotti, F and van Diepen, JA and Rensen, PCN and Netea, MG and Willems van Dijk, K and Berbée, JFP and van Harmelen, V}, title = {BMT decreases HFD-induced weight gain associated with decreased preadipocyte number and insulin secretion.}, journal = {PloS one}, volume = {12}, number = {4}, pages = {e0175524}, pmid = {28445487}, issn = {1932-6203}, mesh = {Adipocytes/*cytology ; Adipose Tissue, White/cytology/immunology/metabolism ; Animals ; *Bone Marrow Transplantation ; C-Peptide/blood ; Diet, Fat-Restricted ; *Diet, High-Fat ; Eating ; Energy Metabolism ; Fatty Acids, Nonesterified/analysis ; Feces/chemistry ; Glucose Tolerance Test ; Insulin/blood/metabolism ; Insulin Secretion ; Macrophages/cytology/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/etiology/prevention &amp; control ; Pancreas/metabolism/pathology ; Triglycerides/analysis ; Weight Gain ; }, abstract = {Experimental bone marrow transplantation (BMT) in mice is commonly used to assess the role of immune cell-specific genes in various pathophysiological settings. The application of BMT in obesity research is hampered by the significant reduction in high-fat diet (HFD)-induced obesity. We set out to characterize metabolic tissues that may be affected by the BMT procedure and impair the HFD-induced response. Male C57BL/6 mice underwent syngeneic BMT using lethal irradiation. After a recovery period of 8 weeks they were fed a low-fat diet (LFD) or HFD for 16 weeks. HFD-induced obesity was reduced in mice after BMT as compared to HFD-fed control mice, characterized by both a reduced fat (-33%; p<0.01) and lean (-11%; p<0.01) mass, while food intake and energy expenditure were unaffected. As compared to control mice, BMT-treated mice had a reduced mature adipocyte volume (approx. -45%; p<0.05) and reduced numbers of preadipocytes (-38%; p<0.05) and macrophages (-62%; p<0.05) in subcutaneous, gonadal and visceral white adipose tissue. In BMT-treated mice, pancreas weight (-46%; p<0.01) was disproportionally decreased. This was associated with reduced plasma insulin (-68%; p<0.05) and C-peptide (-37%; p<0.01) levels and a delayed glucose clearance in BMT-treated mice on HFD as compared to control mice. In conclusion, the reduction in HFD-induced obesity after BMT in mice is at least partly due to alterations in the adipose tissue cell pool composition as well as to a decreased pancreatic secretion of the anabolic hormone insulin. These effects should be considered when interpreting results of experimental BMT in metabolic studies.}, }
@article {pmid28445246, year = {2017}, author = {Jacob, V and Crawford, C and Cohen-Mekelburg, S and Viladomiu, M and Putzel, GG and Schneider, Y and Chabouni, F and OʼNeil, S and Bosworth, B and Woo, V and Ajami, NJ and Petrosino, JF and Gerardin, Y and Kassam, Z and Smith, M and Iliev, ID and Sonnenberg, GF and Artis, D and Scherl, E and Longman, RS}, title = {Single Delivery of High-Diversity Fecal Microbiota Preparation by Colonoscopy Is Safe and Effective in Increasing Microbial Diversity in Active Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {23}, number = {6}, pages = {903-911}, pmid = {28445246}, issn = {1536-4844}, support = {K08 DK099381/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; CD4-Positive T-Lymphocytes/cytology ; Colitis, Ulcerative/*microbiology/*therapy ; Colonoscopy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; New York ; Pilot Projects ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Rectum/pathology ; Remission Induction ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Recent trials suggest fecal microbiota transplantation (FMT) with repeated enemas and high-diversity FMT donors is a promising treatment to induce remission in ulcerative colitis.<br><br>METHODS: We designed a prospective, open-label pilot study to assess the safety, clinical efficacy, and microbial engraftment of single FMT delivery by colonoscopy for active ulcerative colitis using a 2-donor fecal microbiota preparation (FMP). Safety and clinical endpoints of response, remission, and mucosal healing at week 4 were assessed. Fecal DNA and rectal biopsies were used to characterize the microbiome and mucosal CD4 T cells, respectively, before and after FMT.<br><br>RESULTS: Of the 20 patients enrolled in this study, 7 patients (35%) achieved a clinical response by week 4. Three patients (15%) were in remission at week 4 and 2 of these patients (10%) achieved mucosal healing. Three patients (15%) required escalation of care. No serious adverse events were observed. Microbiome analysis revealed that restricted diversity of recipients pre-FMT was significantly increased by high-diversity 2-donor FMP. The microbiome of recipients post-transplant was more similar to the donor FMP than the pretransplant recipient sample in both responders and nonresponders. Notably, donor composition correlated with clinical response. Mucosal CD4 T-cell analysis revealed a reduction in both Th1 and regulatory T-cells post-FMT.<br><br>CONCLUSIONS: High-diversity, 2-donor FMP delivery by colonoscopy seems safe and effective in increasing fecal microbial diversity in patients with active ulcerative colitis. Donor composition correlated with clinical response and further characterization of immunological parameters may provide insight into factors influencing clinical outcome.}, }
@article {pmid28444508, year = {2017}, author = {Aarnoutse, R and de Vos-Geelen, JMPGM and Penders, J and Boerma, EG and Warmerdam, FARM and Goorts, B and Olde Damink, SWM and Soons, Z and Rensen, SSM and Smidt, ML}, title = {Study protocol on the role of intestinal microbiota in colorectal cancer treatment: a pathway to personalized medicine 2.0.}, journal = {International journal of colorectal disease}, volume = {32}, number = {7}, pages = {1077-1084}, pmid = {28444508}, issn = {1432-1262}, mesh = {Bevacizumab/pharmacology/therapeutic use ; Capecitabine/pharmacology/therapeutic use ; Clinical Trials as Topic ; Colorectal Neoplasms/drug therapy/*microbiology/*therapy ; *Gastrointestinal Microbiome ; Humans ; *Precision Medicine ; }, abstract = {PURPOSE: Investigate in patients with metastatic and/or irresectable colorectal cancer treated with systemic treatment with capecitabine or TAS-102 whether: 1. Intestinal microbiota composition can act as a predictor for response. 2. Intestinal microbiota composition changes during systemic treatment and its relation to chemotoxicity.<br><br>BACKGROUND: Gut microbiota and host determinants evolve in symbiotic and dependent relationships resulting in a personal ecosystem. In vitro studies showed prolonged and increased response to 5-fluorouracil, a fluoropyrimidine, in the presence of a favorable microbiota composition. Capecitabine and TAS-102 are both fluoropyrimidines used for systemic treatment in colorectal cancer patients.<br><br>METHODS: An explorative prospective multicenter cohort study in the Maastricht University Medical Centre+ and Zuyderland Medical Centre will be performed in 66 patients. Before, during, and after three cycles of systemic treatment with capecitabine or TAS-102, fecal samples and questionnaires (concerning compliance and chemotoxicity) will be collected. The response will be measured by CT/MRI using RECIST-criteria. Fecal microbiota composition will be analyzed with 16S rRNA next-generation sequencing. The absolute bacterial abundance will be assessed with quantitative polymerase chain reaction. Multivariate analysis will be used for statistical analysis.<br><br>CONCLUSIONS: We aim to detect a microbiota composition that predicts if patients with metastatic and/or irresectable colorectal cancer will respond to systemic treatment and/or experience zero to limited chemotoxicity. If we are able to identify a favorable microbiota composition, fecal microbiota transplantation might be the low-burden alternative to chemotherapy switch in the future.}, }
@article {pmid28442436, year = {2017}, author = {Ayubi, E and Safiri, S}, title = {"Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a three-year cohort study"; methodological issues.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {23}, number = {11}, pages = {890}, doi = {10.1016/j.cmi.2017.04.017}, pmid = {28442436}, issn = {1469-0691}, mesh = {Clostridioides difficile ; Clostridium Infections/*microbiology ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Recurrence ; }, }
@article {pmid28438965, year = {2018}, author = {Gerassy-Vainberg, S and Blatt, A and Danin-Poleg, Y and Gershovich, K and Sabo, E and Nevelsky, A and Daniel, S and Dahan, A and Ziv, O and Dheer, R and Abreu, MT and Koren, O and Kashi, Y and Chowers, Y}, title = {Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction.}, journal = {Gut}, volume = {67}, number = {1}, pages = {97-107}, doi = {10.1136/gutjnl-2017-313789}, pmid = {28438965}, issn = {1468-3288}, mesh = {Animals ; Coculture Techniques ; Colitis/*etiology/immunology/microbiology ; Cytokines/*biosynthesis ; Disease Susceptibility ; Dysbiosis/*etiology/immunology/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*radiation effects ; Germ-Free Life ; Intestinal Mucosa/immunology/microbiology ; Mice, Inbred C57BL ; Proctitis/etiology/immunology/microbiology ; Radiation Injuries/immunology/*microbiology ; Rectum/immunology/microbiology/radiation effects ; }, abstract = {OBJECTIVE: Radiation proctitis (RP) is a complication of pelvic radiotherapy which affects both the host and microbiota. Herein we assessed the radiation effect on microbiota and its relationship to tissue damage using a rectal radiation mouse model.<br><br>DESIGN: We evaluated luminal and mucosa-associated dysbiosis in irradiated and control mice at two postradiation time points and correlated it with clinical and immunological parameters. Epithelial cytokine response was evaluated using bacterial-epithelial co-cultures. Subsequently, germ-free (GF) mice were colonised with postradiation microbiota and controls and exposed to radiation, or dextran sulfate-sodium (DSS). Interleukin (IL)-1&#x3b2; correlated with tissue damage and was induced by dysbiosis. Therefore, we tested its direct role in radiation-induced damage by IL-1 receptor antagonist administration to irradiated mice.<br><br>RESULTS: A postradiation shift in microbiota was observed. A unique microbial signature correlated with histopathology. Increased colonic tumor necrosis factor (TNF)&#x3b1;, IL-1&#x3b2; and IL-6 expression was observed at two different time points. Adherent microbiota from RP differed from those in uninvolved segments and was associated with tissue damage. Using bacterial-epithelial co-cultures, postradiation microbiota enhanced IL-1&#x3b2; and TNF&#x3b1; expression compared with na&#xef;ve microbiota. GF mice colonisation by irradiated microbiota versus controls predisposed mice to both radiation injury and DSS-induced colitis. IL-1 receptor antagonist administration ameliorated intestinal radiation injury.<br><br>CONCLUSIONS: The results demonstrate that rectal radiation induces dysbiosis, which transmits radiation and inflammatory susceptibility and provide evidence that microbial-induced radiation tissue damage is at least in part mediated by IL-1&#x3b2;. Environmental factors may affect the host via modifications of the microbiome and potentially allow for novel interventional approaches via its manipulation.}, }
@article {pmid28438442, year = {2017}, author = {Tavalla, M and Mardani-Kateki, M and Abdizadeh, R and Nashibi, R and Rafie, A and Khademvatan, S}, title = {Molecular identification of Enterocytozoon bieneusi and Encephalitozoon spp. in immunodeficient patients in Ahvaz, Southwest of Iran.}, journal = {Acta tropica}, volume = {172}, number = {}, pages = {107-112}, doi = {10.1016/j.actatropica.2017.04.015}, pmid = {28438442}, issn = {1873-6254}, mesh = {Animals ; Encephalitozoon/*genetics ; Enterocytozoon/*genetics ; Feces/parasitology ; Genotype ; Humans ; *Immunocompromised Host ; Iran/epidemiology ; Microsporidiosis/epidemiology/*parasitology ; Polymerase Chain Reaction/methods ; Polymorphism, Restriction Fragment Length ; Prevalence ; }, abstract = {Microsporidia are often considered as an opportunistic infection in patients with impaired immune systems such as transplant recipients and patients with acquired immune deficiency syndrome (AIDS). Due to the increasing prevalence of parasitic infections and immunodeficiency diseases; the aim of the study is to evaluate molecular identification of Enterocytozoon bieneusi and Encephalitozoon spp. in immunodeficient patients in Ahvaz, southwest of Iran. At first, 310 stool samples were collected from patients with immunodeficiency. The specimens were stained by modified trichrome (weber) and were examined microscopically. The extracted DNA samples were evaluated by multiplex/nested PCR method. The products of multiplex/nested PCR were explored by RFLP method using the restriction enzyme of Mnl1. Of 310, 93 samples were suspected positive for microsporidia by the staining. Also, of 310, 88 samples were positive by the multiplex/nested-PCR test that 62 samples were positive for E. bieneusi as well as 26 were detected as Encephalitozoon species that including 3 E. cuniculi, 19 E. intestinalis and 4 E. hellem. Of 62 E. bieneusi, 45, 16 and 1 were detected as genotype D, M and WL11, respectively. Also, Of 3 E. cuniculi, 1 and 2 cases were identified as genotype I and II, respectively. All E. hellem samples were included genotype 1A. Our findings revealed a relatively high prevalence of microsporidia species in immunodeficient patients. The highest risk of this infection is at individuals with impaired immune systems that it can be life-threatening in people with immune system dysfunction. It is essential that the high-risk people should be receiving the information about the risk of direct contact with infected individuals and animals.}, }
@article {pmid28438184, year = {2017}, author = {Fleming, C and Cai, Y and Sun, X and Jala, VR and Xue, F and Morrissey, S and Wei, YL and Chien, YH and Zhang, HG and Haribabu, B and Huang, J and Yan, J}, title = {Microbiota-activated CD103[+] DCs stemming from microbiota adaptation specifically drive γδT17 proliferation and activation.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {46}, pmid = {28438184}, issn = {2049-2618}, mesh = {Animals ; Antigens, CD/metabolism ; Bacteria/classification/genetics/*growth &amp; development/isolation &amp; purification ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Dendritic Cells/*immunology ; Gastrointestinal Microbiome ; Integrin alpha Chains/metabolism ; Mice ; Mice, Knockout ; Microbiota ; Mouth/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Receptors, Interleukin-17/genetics ; Sequence Analysis, DNA/methods ; Th17 Cells/*immunology ; }, abstract = {BACKGROUND: IL-17-producing γδT cells (γδT17) promote autoinflammatory diseases and cancers. Yet, γδT17 peripheral regulation has not been thoroughly explored especially in the context of microbiota-host interaction. The potent antigen-presenting CD103[+] dendritic cell (DC) is a key immune player in close contact with both γδT17 cells and microbiota. This study presents a novel cellular network among microbiota, CD103[+] DCs, and γδT17 cells.<br><br>METHODS: Immunophenotyping of IL-17r[-/-] mice and IL-17r[-/-] IRF8[-/-] mice were performed by ex vivo immunostaining and flow cytometric analysis. We observed striking microbiome differences in the oral cavity and gut of IL-17r[-/-] mice by sequencing 16S rRNA gene (v1-v3 region) and analyzed using QIIME 1.9.0 software platform. Principal coordinate analysis of unweighted UniFrac distance matrix showed differential clustering for WT and IL-17r[-/-] mice.<br><br>RESULTS: We found drastic homeostatic expansion of &#x3b3;&#x3b4;T17 in all major tissues, most prominently in cervical lymph nodes (cLNs) with monoclonal expansion of V&#x3b3;6 &#x3b3;&#x3b4;T17 in IL-17r[-/-] mice. Ki-67 staining and in vitro CFSE assays showed cellular proliferation due to cell-to-cell contact stimulation with microbiota-activated CD103[+] DCs. A newly developed double knockout mice model for IL-17r and CD103[+] DCs (IL-17r[-/-]IRF8[-/-]) showed a specific reduction in V&#x3b3;6 &#x3b3;&#x3b4;T17. V&#x3b3;6 &#x3b3;&#x3b4;T17 expansion is inhibited in germ-free mice and antibiotic-treated specific pathogen-free (SPF) mice. Microbiota transfer using cohousing of IL-17r[-/-] mice with wildtype mice induces &#x3b3;&#x3b4;T17 expansion in the wildtype mice with increased activated CD103[+] DCs in cLNs. However, microbiota transfer using fecal transplant through oral gavage to bypass the oral cavity showed no difference in colon or systemic &#x3b3;&#x3b4;T17 expansion.<br><br>CONCLUSIONS: These findings reveal for the first time that &#x3b3;&#x3b4;T17 cells are regulated by microbiota dysbiosis through cell-to-cell contact with activated CD103[+] DCs leading to drastic systemic, monoclonal expansion. Microbiota dysbiosis, as indicated by drastic bacterial population changes at the phylum and genus levels especially in the oral cavity, was discovered in mice lacking IL-17r. This network could be very important in regulating both microbiota and immune players. This critical regulatory pathway for &#x3b3;&#x3b4;T17 could play a major role in IL-17-driven inflammatory diseases and needs further investigation to determine specific targets for future therapeutic intervention.}, }
@article {pmid28434033, year = {2017}, author = {Brunkwall, L and Orho-Melander, M}, title = {The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities.}, journal = {Diabetologia}, volume = {60}, number = {6}, pages = {943-951}, pmid = {28434033}, issn = {1432-0428}, mesh = {Diabetes Mellitus, Type 2/drug therapy/genetics/*metabolism/*microbiology ; Feces/microbiology ; Gastrointestinal Microbiome/genetics/*radiation effects ; Humans ; Metformin/therapeutic use ; }, abstract = {The totality of microbial genomes in the gut exceeds the size of the human genome, having around 500-fold more genes that importantly complement our coding potential. Microbial genes are essential for key metabolic processes, such as the breakdown of indigestible dietary fibres to short-chain fatty acids, biosynthesis of amino acids and vitamins, and production of neurotransmitters and hormones. During the last decade, evidence has accumulated to support a role for gut microbiota (analysed from faecal samples) in glycaemic control and type 2 diabetes. Mechanistic studies in mice support a causal role for gut microbiota in metabolic diseases, although human data favouring causality is insufficient. As it may be challenging to sort the human evidence from the large number of animal studies in the field, there is a need to provide a review of human studies. Thus, the aim of this review is to cover the current and future possibilities and challenges of using the gut microbiota, with its capacity to be modified, in the development of preventive and treatment strategies for hyperglycaemia and type 2 diabetes in humans. We discuss what is known about the composition and functionality of human gut microbiota in type 2 diabetes and summarise recent evidence of current treatment strategies that involve, or are based on, modification of gut microbiota (diet, probiotics, metformin and bariatric surgery). We go on to review some potential future gut-based glucose-lowering approaches involving microbiota, including the development of personalised nutrition and probiotic approaches, identification of therapeutic components of probiotics, targeted delivery of propionate in the proximal colon, targeted delivery of metformin in the lower gut, faecal microbiota transplantation, and the incorporation of genetically modified bacteria that express therapeutic factors into microbiota. Finally, future avenues and challenges for understanding the interplay between human nutrition, genetics and microbial genetics, and the need for integration of human multi-omic data (such as genetics, transcriptomics, epigenetics, proteomics and metabolomics) with microbiome data (such as strain-level variation, transcriptomics, proteomics and metabolomics) to make personalised treatments a successful future reality are discussed.}, }
@article {pmid28433406, year = {2017}, author = {López-Sanromán, A and Rodríguez de Santiago, E and Cobo Reinoso, J and Del Campo Moreno, R and Foruny Olcina, JR and García Fernández, S and García García de Paredes, A and Aguilera Castro, L and Ferre Aracil, C and Albillos Martínez, A}, title = {Results of the implementation of a multidisciplinary programme of faecal microbiota transplantation by colonoscopy for the treatment of recurrent Clostridium difficile infection.}, journal = {Gastroenterologia y hepatologia}, volume = {40}, number = {9}, pages = {605-614}, doi = {10.1016/j.gastrohep.2017.03.004}, pmid = {28433406}, issn = {0210-5705}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; *Colonoscopy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Humans ; Middle Aged ; Program Evaluation ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {INTRODUCTION: Recurrent Clostridium difficile infection (CDI) is common and often difficult to manage. Faecal microbiota transplant (FMT) is an effective therapeutic tool in these cases, although its applicability and effectiveness in Spain is currently unknown.<br><br>AIM: To analyse the technical aspects, safety and effectiveness of the first consolidated FMT programme in Spain.<br><br>METHODS: Retrospective descriptive study of all patients with recurrent CDI treated with FMT performed by colonoscopy in a tertiary centre after the implementation of a multidisciplinary protocol between March 2015 and September 2016.<br><br>RESULTS: A total of 13 FMT were performed in 12 patients (11/12; 91.7% women) with a median age of 84.6 years (range: 38.2-98.2). Recurrence of CDI was the indication for FMT in all cases. Patients had suffered a median of 3 previous episodes of CDI (range: 2-6) and all had failed treatment with fidaxomicin. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 91.7% (11/12; 95% CI: 64.6 to 98.5%). In the non-responder patient, a second FMT was performed 17 days after the first procedure, with disappearance of symptoms. No side effects related to the endoscopic procedure or the FMT were recorded after a median follow-up of 6.5 months (range: 1-16 months). Two patients died during follow-up due to causes unrelated to FMT.<br><br>CONCLUSION: FMT by colonoscopy is an effective and safe therapeutic alternative in recurrent CDI. It is a simple procedure that should be implemented in more centres in Spain.}, }
@article {pmid28430696, year = {2017}, author = {Arulkumaran, N and Sixma, ML and Jentho, E and Ceravola, E and Bass, PS and Kellum, JA and Unwin, RJ and Tam, FWK and Singer, M}, title = {Sequential Analysis of a Panel of Biomarkers and Pathologic Findings in a Resuscitated Rat Model of Sepsis and Recovery.}, journal = {Critical care medicine}, volume = {45}, number = {8}, pages = {e821-e830}, pmid = {28430696}, issn = {1530-0293}, support = {//Wellcome Trust/United Kingdom ; 093969//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biomarkers ; Cell Adhesion Molecules/urine ; Cystatin C/blood ; Disease Models, Animal ; Hemodynamics ; Inflammation Mediators/metabolism ; Kidney Function Tests ; Lipocalin-2/urine ; Lipocalins/urine ; Male ; Prospective Studies ; Rats ; Rats, Wistar ; Sepsis/blood/*physiopathology/urine ; Time Factors ; }, abstract = {OBJECTIVES: To characterize the temporal pattern of a panel of blood and urinary biomarkers in an animal model of fecal peritonitis and recovery.<br><br>DESIGN: Prospective observational animal study.<br><br>SETTING: University research laboratory.<br><br>SUBJECTS: Male Wistar rats.<br><br>INTERVENTIONS: A fluid-resuscitated, long-term (3 d) rat model of sepsis (fecal peritonitis) and recovery was used to understand the temporal association of sepsis biomarkers in relation to systemic hemodynamics, inflammation, and renal function. At predefined time points (3, 6, 12, 24, 48, 72&#x2009;hr), animals (&#x2265; 6 per group) underwent echocardiography, blood and urine sampling, and had kidneys taken for histological analysis. Comparison was made against sham-operated controls and na&#xef;ve animals.<br><br>MEASUREMENTS AND MAIN RESULTS: The systemic proinflammatory response was maximal at 6 hours, corresponding with the nadir of stroke volume. Serum creatinine peaked late (24&#x2009;hr), when clinical recovery was imminent. Histological evidence of tubular injury and cell death was minimal. After a recovery period, all biomarkers returned to levels approaching those observed in sham animals. Apart from urine clusterin and interleukin-18, all other urinary biomarkers were elevated at earlier time points compared with serum creatinine. Urine neutrophil gelatinase-associated lipocalin was the most sensitive marker among those studied, rising from 3 hours. While serum creatinine fell at 12 hours, serum cystatin C increased, suggestive of decreased creatinine production.<br><br>CONCLUSIONS: Novel information is reported on the temporal profile of a panel of renal biomarkers in sepsis in the context of systemic and renal inflammation and recovery. Insight into the pathophysiology of acute kidney injury is gleaned from the temporal change markers of renal injury (urine neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, calbindin), followed by a marker of cell cycle arrest (urine insulin-like growth factor-binding protein 7) and, finally, by functional markers of filtration (serum creatinine and cystatin C). These clinically relevant findings should have significant influence on future clinical testing.}, }
@article {pmid28430073, year = {2017}, author = {Bunnik, EM and Aarts, N and Chen, LA}, title = {Physicians Must Discuss Potential Long-Term Risks of Fecal Microbiota Transplantation to Ensure Informed Consent.}, journal = {The American journal of bioethics : AJOB}, volume = {17}, number = {5}, pages = {61-63}, doi = {10.1080/15265161.2017.1299816}, pmid = {28430073}, issn = {1536-0075}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Informed Consent ; Physicians ; Risk ; }, }
@article {pmid28430066, year = {2017}, author = {Rhodes, R and Sacks, H}, title = {Cautions for Extending Fecal Microbiota Transplantation to Other Therapeutic Uses.}, journal = {The American journal of bioethics : AJOB}, volume = {17}, number = {5}, pages = {46-48}, doi = {10.1080/15265161.2017.1299251}, pmid = {28430066}, issn = {1536-0075}, mesh = {*Fecal Microbiota Transplantation ; Humans ; Treatment Outcome ; }, }
@article {pmid28430065, year = {2017}, author = {Ma, Y and Liu, J and Rhodes, C and Nie, Y and Zhang, F}, title = {Ethical Issues in Fecal Microbiota Transplantation in Practice.}, journal = {The American journal of bioethics : AJOB}, volume = {17}, number = {5}, pages = {34-45}, doi = {10.1080/15265161.2017.1299240}, pmid = {28430065}, issn = {1536-0075}, mesh = {Beneficence ; *Bioethical Issues ; Clostridium Infections/*therapy ; Ethical Analysis ; Fecal Microbiota Transplantation/*ethics ; Health Personnel ; Humans ; Informed Consent ; *Policy ; Public Health ; Risk ; *Social Control, Formal ; Tissue Donors ; }, abstract = {Fecal microbiota transplantation (FMT) has demonstrated efficacy and is increasingly being used in the treatment of patients with recurrent Clostridium difficile infection. Despite a lack of high-quality trials to provide more information on the long-term effects of FMT, there has been great enthusiasm about the potential for expanding its applications. However, FMT presents many serious ethical and social challenges that must be addressed as part of a successful regulatory policy response. In this article, we draw on a sample of the scientific and bioethics literatures to examine clusters of ethical and social issues arising in five main areas: (1) informed consent and the vulnerability of patients; (2) determining what a "suitable healthy donor" is; (3) safety and risk; (4) commercialization and potential exploitation of vulnerable patients; and (5) public health implications. We find that these issues are complex and worthy of careful consideration by health care professionals. Desperation of a patient should not be the basis for selecting treatment with FMT, and the patient's interests should always be of paramount concern. Authorities must prioritize development of appropriate and effective regulation of FMT to safeguard patients and donors, promote further research into safety and efficacy, and avoid abuse of the treatment.}, }
@article {pmid28430064, year = {2017}, author = {Scanlan, C and Kerridge, I}, title = {Aesthetics, Ethics, and Fecal Microbiota Transplantations.}, journal = {The American journal of bioethics : AJOB}, volume = {17}, number = {5}, pages = {51-52}, doi = {10.1080/15265161.2017.1299250}, pmid = {28430064}, issn = {1536-0075}, mesh = {Esthetics ; *Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid28430063, year = {2017}, author = {Haw, J and Chuong, K and O'Doherty, KC}, title = {FMT Regulatory Challenges and the Lived Experiences of People With IBD.}, journal = {The American journal of bioethics : AJOB}, volume = {17}, number = {5}, pages = {59-61}, doi = {10.1080/15265161.2017.1299253}, pmid = {28430063}, issn = {1536-0075}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases ; }, }
@article {pmid28430060, year = {2017}, author = {Bokek-Cohen, Y and Ravitsky, V}, title = {Cultural and Personal Considerations in Informed Consent for Fecal Microbiota Transplantation.}, journal = {The American journal of bioethics : AJOB}, volume = {17}, number = {5}, pages = {55-57}, doi = {10.1080/15265161.2017.1299241}, pmid = {28430060}, issn = {1536-0075}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Informed Consent ; }, }
@article {pmid28430058, year = {2017}, author = {Huss, J}, title = {Fecal Transplant Bioethics: Beyond Chicken Little.}, journal = {The American journal of bioethics : AJOB}, volume = {17}, number = {5}, pages = {48-50}, doi = {10.1080/15265161.2017.1299254}, pmid = {28430058}, issn = {1536-0075}, mesh = {Humans ; Bioethics ; *Fecal Microbiota Transplantation ; }, }
@article {pmid28430054, year = {2017}, author = {Metselaar, S and Widdershoven, G}, title = {Ethical Issues in Fecal Microbiota Transplantion: Taking Into Account Identity and Family Relations.}, journal = {The American journal of bioethics : AJOB}, volume = {17}, number = {5}, pages = {53-55}, doi = {10.1080/15265161.2017.1299245}, pmid = {28430054}, issn = {1536-0075}, mesh = {*Family Relations ; Feces ; Humans ; *Microbiota ; }, }
@article {pmid28429164, year = {2017}, author = {Otto, CC and Chen, LH and He, T and Tang, YW and Babady, NE}, title = {Detection of gastrointestinal pathogens in oncology patients by highly multiplexed molecular panels.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {36}, number = {9}, pages = {1665-1672}, pmid = {28429164}, issn = {1435-4373}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA008748//National Cancer Institute/ ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Feces/microbiology ; Female ; Gastroenteritis/diagnosis/*etiology ; *Gastrointestinal Microbiome ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Male ; Metagenome ; Metagenomics/methods ; Middle Aged ; Neoplasms/*complications/therapy ; Young Adult ; }, abstract = {We compared the frequency of gastrointestinal (GI) pathogen detection in an oncology patient population by two multiplexed molecular assays, the Luminex xTAG® Gastrointestinal Pathogen Panel (GPP, which identifies 14 GI pathogens) and the BioFire Gastrointestinal Panel (BFGP, which identifies 22 GI pathogens). We additionally reviewed the clinical characteristics of patients tested with both panels. A total of 200 prospectively collected and 81 archived stool samples were tested by both panels. In the prospective cohort, the GPP and BFGP identified a pathogen in 33.5% [95% confidence interval (CI): 27.3-40.35%] and 39.6% (95% CI: 33.0%-46.6%) of samples, respectively (p = 0.25). The BFGP detected significantly more pathogens than the GPP (p = 0.038), with 21.3% of samples positive for targets only detected by the BFGP. The concordance between the assays was very good at 91.1% (κ = 0.8, 95% CI: 0.7-0.9) when considering only pathogens detected by both assays. The most frequent pathogens detected were Clostridium difficile, norovirus, Campylobacter, and Salmonella species. On the archived samples, the BFGP was positive in 92.6% of samples but detected more pathogens than the GPP (86 vs. 97, p = 0.033), including both targets unique to the BFGP and targets common to both panels. A pathogen was more frequently detected in patients with hematological malignancies than solid tumors and in ambulatory patients compared to hospitalized patients, but these differences were not statistically significant. Overall, the detection rates were similar for both the GPP and the BFGP, and the latter detected more than one pathogen in additional patients. The impact of increased detection of GI pathogens by multiplexed panels on the clinical care of oncology patients will require further investigation.}, }
@article {pmid28426649, year = {2017}, author = {Walker, WA}, title = {The importance of appropriate initial bacterial colonization of the intestine in newborn, child, and adult health.}, journal = {Pediatric research}, volume = {82}, number = {3}, pages = {387-395}, pmid = {28426649}, issn = {1530-0447}, support = {P01 DK033506/DK/NIDDK NIH HHS/United States ; P30 DK040561/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Bacteria/growth &amp; development/*isolation &amp; purification ; Breast Feeding ; Child ; Dysbiosis/prevention &amp; control ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; }, abstract = {The fetus does not reside in a sterile intrauterine environment and is exposed to commensal bacteria from the maternal gut/blood stream that cross the placenta and enter the amniotic fluid. This intestinal exposure to colonizing bacteria continues at birth and during the first year of life and has a profound influence on lifelong health. Why is this important? Intestinal crosstalk with colonizing bacteria in the developing intestine affects the infant's adaptation to extrauterine life (immune homeostasis) and provides protection against disease expression (allergy, autoimmune disease, obesity, etc.) later in life. Colonizing intestinal bacteria are critical to the normal development of host defense. Disrupted colonization (dysbiosis) due to maternal dysbiosis, cesarean section delivery, use of perinatal antibiotics, or premature delivery may adversely affect the gut development of host defense and predispose to inflammation rather than to homeostasis, leading to increased susceptibility to disease later in life. Babies born by cesarean section have a higher incidence of allergy, type 1 diabetes, and obesity. Infants given repeated antibiotic regimens during the first year of life are more likely to have asthma as adolescents. This research breakthrough helps to explain the shift in disease paradigms from infections to immune-mediated in children from developed countries. This review will develop this research breakthrough.}, }
@article {pmid28426476, year = {2018}, author = {Boyer, O and Bridoux, V and Giverne, C and Bisson, A and Koning, E and Leroi, AM and Chambon, P and Déhayes, J and Le Corre, S and Jacquot, S and Bastit, D and Martinet, J and Houivet, E and Tuech, JJ and Benichou, J and Michot, F and , }, title = {Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS).}, journal = {Annals of surgery}, volume = {267}, number = {3}, pages = {443-450}, pmid = {28426476}, issn = {1528-1140}, mesh = {Adult ; Double-Blind Method ; Fecal Incontinence/diagnosis/physiopathology/*therapy ; Female ; Humans ; Injections ; Middle Aged ; Myoblasts/*transplantation ; Prospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate the efficacy of intrasphincteric injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a controlled study.<br><br>SUMMARY OF BACKGROUND DATA: Adult stem cell therapy is expected to definitively cure FI by regenerating damaged sphincter. Preclinical data and results of open-label trials suggest that myoblast therapy may represent a noninvasive treatment option.<br><br>METHODS: We conducted a phase 2 randomized, double-blind, placebo-controlled study of intrasphincteric injections of AM in 24 patients. The study compared outcome after AM (n = 12) or placebo (n = 12) injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months. Patients in the placebo group were eligible to receive frozen AM after 1 year.<br><br>RESULTS: At 6 months, the median CCI score significantly decreased from baseline in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups. Hence, no significant difference was found between the 2 groups (primary endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12 months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12 months.<br><br>CONCLUSIONS: Intrasphincteric AM injections in FI patients have shown tolerance, safety, and clinical benefit at 12 months despite a transient placebo effect at 6 months.}, }
@article {pmid28425133, year = {2017}, author = {Huang, Y and Guo, F and Li, Y and Wang, J and Li, J}, title = {Fecal microbiota signatures of adult patients with different types of short bowel syndrome.}, journal = {Journal of gastroenterology and hepatology}, volume = {32}, number = {12}, pages = {1949-1957}, doi = {10.1111/jgh.13806}, pmid = {28425133}, issn = {1440-1746}, mesh = {Adult ; Amino Acids, Aromatic/biosynthesis ; Amino Acids, Branched-Chain/biosynthesis ; Case-Control Studies ; Citric Acid Cycle ; Dysbiosis ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/metabolism ; Intestines/microbiology ; Lactobacillus ; Male ; Middle Aged ; Prospective Studies ; Purines/metabolism ; Pyrimidines/metabolism ; Short Bowel Syndrome/classification/metabolism/*microbiology ; }, abstract = {BACKGROUND AND AIM: Short bowel syndrome (SBS) is a common cause of intestinal failure and can be divided into three types depending on intestinal anatomy. Gut dysbiosis has been observed in pediatric SBS patients and is associated with impaired outcome. Little is known about the changes in gut microbiota of adult SBS patients. Therefore, we aim to characterize the fecal microbiota of adult patients with different types of SBS.<br><br>METHODS: Fifteen fecal samples from healthy controls and adult patients with type II or type III SBS were collected (five in each group). Fecal microbial compositions were determined by high-throughput sequencing, and functional potential was predicted by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.<br><br>RESULTS: Bacterial &#x3b1;-diversity significantly decreased in SBS patients and positively correlated to the remaining small bowel length. SBS II patients were enriched with Proteobacteria but deficient in Firmicutes and Bacteroidetes. Whereas Lactobacillus and Prevotella dominated the microbiomes of SBS III patients, commensal bacteria from Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae declined in SBS patients. The parenteral nutrition duration of SBS patients was positively related to the proportion of Enterobacteriaceae but negatively related to Lactobacillus. Functional pathways of citrate cycle and branched-chain and aromatic amino acid biosynthesis were abundant in SBS II patients, while functional profiles of pyrimidine and purine metabolism were dominant in SBS III patients.<br><br>CONCLUSIONS: Short bowel syndrome patients have a marked intestinal dysbiosis with type II SBS characterized by Proteobacteria and type III SBS featured by Lactobacillus, resulting in altered functional profiles of fecal microbiomes.}, }
@article {pmid28422836, year = {2017}, author = {Uygun, A and Ozturk, K and Demirci, H and Oger, C and Avci, IY and Turker, T and Gulsen, M}, title = {Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis.}, journal = {Medicine}, volume = {96}, number = {16}, pages = {e6479}, pmid = {28422836}, issn = {1536-5964}, mesh = {Adult ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Colitis, Ulcerative/diagnostic imaging/*therapy ; Colonoscopy ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Follow-Up Studies ; Humans ; Male ; Mesalamine/therapeutic use ; Middle Aged ; Retreatment ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbial transplantation (FMT) provides to replace beneficial bacteria with more favorable microbiomes in recipient with dysbiosis. The aim of the present study was to prospectively investigate the efficacy of FMT by assessing the clinical and endoscopic response in patients with ulcerative colitis (UC) who had failed anti-inflammatory and immunosuppressive therapy.<br><br>METHODS: In this prospective and uncontrolled study, 30 patients with UC were included. All medications except mesalazine were stopped 4 weeks before FMT. Colonoscopy was performed both before and after FMT. To assess the efficacy of FMT, Mayo scores were calculated at week 0 and week 12. A total of 500&#x200a;mL extracted fresh fecal suspension was administered into the 30 to 40&#x200a;cm proximal of terminal ileum of recipients.<br><br>RESULTS: After FMT, 21 of the (70%) 30 patients showed clinical response, and 13 of the 30 (43.3%) patients achieved clinical and endoscopic remission at the week 12. Nine patients (30%) were accepted as a nonresponder at the end of the week 12. There was no significant difference among donors concerning both the rate of clinical remission and clinical response. No adverse events were observed in the majority of patients during FMT and 12 weeks follow-up. Seven patients (23.3%) experienced mild adverse events such as nausea, vomiting, abdominal pain, diarrhea, and fewer after FMT.<br><br>CONCLUSION: FMT could be considered as a promising rescue treatment modality before surgery in patients with refractory UC. Besides, FMT also appears to be definitely safer and more tolerable than the immunosuppressive therapy in patients with UC (NCT02575040).}, }
@article {pmid28421185, year = {2017}, author = {Flannigan, KL and Rajbar, T and Moffat, A and McKenzie, LS and Dicke, F and Rioux, K and Workentine, ML and Louie, TJ and Hirota, SA and Greenway, SC}, title = {Changes in Composition of the Gut Bacterial Microbiome after Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in a Pediatric Heart Transplant Patient.}, journal = {Frontiers in cardiovascular medicine}, volume = {4}, number = {}, pages = {17}, pmid = {28421185}, issn = {2297-055X}, abstract = {The microbiome is increasingly recognized as an important influence on human health and many of the comorbidities that affect patients after solid organ transplantation (SOT) have been shown to involve changes in gut bacterial populations. Thus, microbiome changes in an individual patient may have important health implications after SOT but this area remains understudied. We describe changes in the composition of the fecal microbiome from a pediatric heart transplant recipient before and >2.5 years after he underwent repeated fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI). With both documented episodes of CDI, there was marked loss of bacterial diversity with overgrowth of Proteobacteria (>98.9% of phyla identified) associated with symptomatic colitis that was corrected after FMT. We hypothesize that a second CDI occurring after FMT was related to incomplete restoration of normal bowel flora post-FMT with relative deficiencies of the phyla Firmicutes and Bacteroidetes and the families Lachnospiraceae and Ruminococcaceae. Following the second FMT, there was a gradual shift in gut bacterial composition coincident with the recipient developing lymphonodular hyperplasia of the colon and painless hematochezia that resolved with discontinuation of mycophenolate mofetil (MMF). This case documents dynamic changes in the bacterial microbiome after FMT and suggests that MMF may influence the gut microbiome with consequences for the patient.}, }
@article {pmid28414794, year = {2017}, author = {von Klitzing, E and Ekmekciu, I and Kühl, AA and Bereswill, S and Heimesaat, MM}, title = {Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota.}, journal = {PloS one}, volume = {12}, number = {4}, pages = {e0176144}, pmid = {28414794}, issn = {1932-6203}, mesh = {Adaptive Immunity/immunology ; Animals ; Bacterial Translocation/immunology/physiology ; Female ; Gastrointestinal Microbiome/immunology/*physiology ; Ileitis/immunology/*microbiology/*parasitology ; Ileum/microbiology/*parasitology ; Immunity, Innate/immunology ; Inflammation/immunology/microbiology/parasitology ; Interferon-gamma/immunology ; Interleukin-12/immunology ; Intestinal Mucosa/*microbiology/*parasitology ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/immunology ; RNA, Ribosomal, 16S/metabolism ; Toxoplasma/immunology/*pathogenicity ; }, abstract = {BACKGROUND: Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction.<br><br>Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-&#x3b3;, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum.<br><br>CONCLUSION/SIGNIFICANCE: With respect to the intestinal microbiota composition "humanized" mice display acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation.}, }
@article {pmid28411380, year = {2017}, author = {Roda, A and Aldini, R and Camborata, C and Spinozzi, S and Franco, P and Cont, M and D'Errico, A and Vasuri, F and Degiovanni, A and Maroni, L and Adorini, L}, title = {Metabolic Profile of Obeticholic Acid and Endogenous Bile Acids in Rats with Decompensated Liver Cirrhosis.}, journal = {Clinical and translational science}, volume = {10}, number = {4}, pages = {292-301}, pmid = {28411380}, issn = {1752-8062}, mesh = {Animals ; Bile Acids and Salts/*metabolism/urine ; Biliary Fistula/metabolism/pathology ; Chenodeoxycholic Acid/*analogs &amp; derivatives/metabolism/urine ; Disease Models, Animal ; Feces/chemistry ; Intestinal Mucosa/metabolism ; Intestines/pathology ; Liver/metabolism/pathology ; Liver Cirrhosis/blood/*metabolism/pathology ; Male ; Metabolome ; *Metabolomics ; Rats, Wistar ; Tissue Distribution ; }, abstract = {Obeticholic acid (OCA) is a semisynthetic bile acid (BA) analog and potent farnesoid X receptor agonist approved to treat cholestasis. We evaluated the biodistribution and metabolism of OCA administered to carbon tetrachloride-induced cirrhotic rats. This was to ascertain if plasma and hepatic concentrations of OCA are potentially more harmful than those of endogenous BAs. After administration of OCA (30 mg/kg), we used liquid chromatography-mass spectrometry to measure OCA, its metabolites, and BAs at different timepoints in various organs and fluids. Plasma and hepatic concentrations of OCA and BAs were higher in cirrhotic rats than in controls. OCA and endogenous BAs had similar metabolic pathways in cirrhotic rats, although OCA hepatic and intestinal clearance were lower than in controls. BAs' qualitative and quantitative compositions were not modified by a single administration of OCA. In all the matrices studied, OCA concentrations were significantly lower than those of endogenous BAs, potentially much more cytotoxic.}, }
@article {pmid28411069, year = {2018}, author = {Dunwoody, R and Steel, A and Landy, J and Simmonds, N}, title = {Clostridium difficile and cystic fibrosis: management strategies and the role of faecal transplantation.}, journal = {Paediatric respiratory reviews}, volume = {26}, number = {}, pages = {16-18}, doi = {10.1016/j.prrv.2017.03.003}, pmid = {28411069}, issn = {1526-0550}, mesh = {Anti-Bacterial Agents/*adverse effects/therapeutic use ; *Clostridium Infections/etiology/therapy ; Cystic Fibrosis/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Patient Care Management/methods ; }, abstract = {Clostridium difficile is a bacterial infection that colonises the gut in susceptible hosts. It is associated with exposure to healthcare settings and antibiotic use. It could be assumed that cystic fibrosis (CF) patients are a high-risk group for C.difficile. However, despite high carriage rates, CF patients have low rates of active disease. There are guidelines for the treatment of C.difficile, however little is published specific to treating C.difficile in CF. This article provides an overview of the current management strategies for C.difficile in CF, including a description of the first faecal transplantation in this patient population.}, }
@article {pmid28406214, year = {2017}, author = {Callaway, E}, title = {'Young poo' makes aged fish live longer.}, journal = {Nature}, volume = {544}, number = {7649}, pages = {147}, doi = {10.1038/nature.2017.21770}, pmid = {28406214}, issn = {1476-4687}, mesh = {*Aging/immunology/physiology ; Animals ; Drosophila melanogaster ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Fundulidae/immunology/*microbiology/*physiology ; Gastrointestinal Tract/immunology/microbiology ; *Longevity/immunology/physiology ; Mice ; Models, Biological ; Rejuvenation ; }, }
@article {pmid28405695, year = {2017}, author = {Salzberger, B and Lehnert, H and Mössner, J}, title = {[The human microbiome].}, journal = {Der Internist}, volume = {58}, number = {5}, pages = {427-428}, doi = {10.1007/s00108-017-0230-3}, pmid = {28405695}, issn = {1432-1289}, mesh = {Autoimmune Diseases/immunology/microbiology/physiopathology ; Biomedical Research ; Clostridium Infections/microbiology/therapy ; Energy Metabolism/immunology/physiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Feeding Behavior ; Humans ; Intestines/immunology/*microbiology ; Metabolic Diseases/microbiology/physiopathology ; Microbiota/genetics/immunology/*physiology ; }, }
@article {pmid28405600, year = {2017}, author = {Kato, K and Nagao, M and Miyamoto, K and Oka, K and Takahashi, M and Yamamoto, M and Matsumura, Y and Kaido, T and Uemoto, S and Ichiyama, S}, title = {Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation.}, journal = {Transplantation direct}, volume = {3}, number = {4}, pages = {e144}, pmid = {28405600}, issn = {2373-8731}, abstract = {BACKGROUND: Increasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown.<br><br>METHODS: We prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively.<br><br>RESULTS: Three hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides, Enterobacteriaceae, Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae, Lactobacillaceae, Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients.<br><br>CONCLUSIONS: The microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes.}, }
@article {pmid28403755, year = {2017}, author = {Morrison, M and Holtmann, G}, title = {Translating our microbiome into medicine.}, journal = {The Medical journal of Australia}, volume = {206}, number = {7}, pages = {287-288}, doi = {10.5694/mja17.00087}, pmid = {28403755}, issn = {1326-5377}, mesh = {Animals ; Disease Models, Animal ; Duodenum/*microbiology ; Dyspepsia/*microbiology ; Fecal Microbiota Transplantation ; Genomics ; Germ-Free Life ; Humans ; Intestinal Mucosa/*microbiology ; Microbiota/*genetics/physiology ; RNA, Ribosomal, 16S/*genetics ; Streptococcus ; Translational Research, Biomedical ; }, }
@article {pmid28400698, year = {2017}, author = {Mehta, A and Afshar, R and Warner, DL and Gardner, A and Ackerman, E and Brandt, J and Sasse, KC}, title = {Laparoscopic Rectopexy with Urinary Bladder Xenograft Reinforcement.}, journal = {JSLS : Journal of the Society of Laparoendoscopic Surgeons}, volume = {21}, number = {1}, pages = {}, pmid = {28400698}, issn = {1938-3797}, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Female ; Follow-Up Studies ; Heterografts/*transplantation ; Humans ; Laparoscopy/*methods ; Male ; Middle Aged ; Rectal Prolapse/*surgery ; Rectum/*surgery ; Recurrence ; Transplantation, Heterologous/*methods ; Treatment Outcome ; Urinary Bladder/*transplantation ; }, abstract = {BACKGROUND AND OBJECTIVES: Rectal prolapse is often repaired laparoscopically, frequently with the use of reinforcement material. Both synthetic and biologically derived materials reduce recurrence rate compared to primary suture repair. Synthetic mesh introduces potential complications such as mesh erosion, fibrosis, and infection. Urinary bladder matrix (UBM) represents a biologically derived material for reinforcement of rectal prolapse repair with the potential to improve durability without risks of synthetic materials. The objective of the study is to evaluate the effectiveness, durability, and functional result of laparoscopic rectopexy using urinary bladder matrix xenograft reinforcement at three years follow up.<br><br>METHODS: The 20 cases presented describe rectal prolapse repair by means of laparoscopic rectopexy with presacral UBM reinforcement. Patients were followed up for an average of 3 years and assessed with interviews, physical examination, manometry, and the fecal incontinence severity index (FISI).<br><br>RESULTS: Each repair was completed laparoscopically. UBM exhibited favorable handling characteristics when sutured to the sacrum and the lateral rectal walls. One patient underwent laparoscopic drainage of a postoperative abscess; no other complications occurred. In 3 years of follow-up, there have been no full-thickness recurrences, erosions, reoperations, or long-term complications. Two patients exhibited a small degree of mucosal prolapse on follow-up physical examination that did not require surgery. Three-year FISI scores averaged 8 (range, 0-33 of a possible 61), indicating low fecal incontinence symptomatology. Follow-up anorectal manometry was performed in 9 patients, showing mixed results.<br><br>CONCLUSION: Surgeons may safely use laparoscopic rectopexy with UBM reinforcement for repair of rectal prolapses. In this series, repairs with UBM grafts have been durable at 3-year follow-up and may be an alternative to synthetic mesh reinforcement of rectal prolapse repairs. Future studies may compare the advantages and cost-effectiveness of reinforcement materials for rectal prolapse repair.}, }
@article {pmid28398347, year = {2017}, author = {Fuentes, S and Rossen, NG and van der Spek, MJ and Hartman, JH and Huuskonen, L and Korpela, K and Salojärvi, J and Aalvink, S and de Vos, WM and D'Haens, GR and Zoetendal, EG and Ponsioen, CY}, title = {Microbial shifts and signatures of long-term remission in ulcerative colitis after faecal microbiota transplantation.}, journal = {The ISME journal}, volume = {11}, number = {8}, pages = {1877-1889}, pmid = {28398347}, issn = {1751-7370}, mesh = {Adult ; Bacteria/genetics ; Chronic Disease ; Colitis, Ulcerative/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Male ; Microbiota ; Middle Aged ; Phylogeny ; }, abstract = {Faecal microbiota transplantation (FMT) may contribute towards disease remission in ulcerative colitis (UC), but it is unknown which factors determine long-term effect of treatment. Here, we aimed to identify bacterial signatures associated with sustained remission. To this end, samples from healthy donors and UC patients-grouped into responders and non-responders at a primary end point (week 12) and further stratified by sustained clinical remission and relapse assessed at ⩾1-year follow-up were analysed, comparing the efficacy of FMT from either a healthy donor or autologous faeces. Microbiota composition was determined with a 16S rRNA gene-based phylogenetic microarray on faecal and mucosal samples, and functional profiles were predicted using PICRUSt with quantitative PCR verification of the butyrate production capacity; short-chain fatty acids were measured in faecal samples. At baseline, UC patients showed reduced amounts of bacterial groups from the Clostridium cluster XIVa, and significantly higher levels of Bacteroidetes as compared with donors. These differences were reduced after FMT mostly in responders. Sustained remission was associated with known butyrate producers and overall increased butyrate production capacity, while relapse was associated with Proteobacteria and Bacteroidetes. Ruminococcus gnavus was found at high levels in donors of failed FMT. A microbial ecosystem rich in Bacteroidetes and Proteobacteria and low in Clostridium clusters IV and XIVa observed in UC patients after FMT was predictive of poor sustained response, unless modified with a donor microbiota rich in specific members from the Clostridium clusters IV and XIVa. Additionally, sustained response was associated with restoration of the butyrate production capacity.}, }
@article {pmid28394706, year = {2017}, author = {Khoruts, A}, title = {Fecal microbiota transplantation-early steps on a long journey ahead.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {199-204}, pmid = {28394706}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Donor Selection ; Drug Resistance, Bacterial ; Dysbiosis/microbiology/*therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; }, }
@article {pmid28391449, year = {2017}, author = {Marti, L and Galata, C and Beutner, U and Hetzer, F and Pipitone, N and Wolff, K and Borovicka, J and Brunner, W and Sulz, MC and Maurus, C}, title = {Percutaneous tibial nerve stimulation (pTNS): success rate and the role of rectal capacity.}, journal = {International journal of colorectal disease}, volume = {32}, number = {6}, pages = {789-796}, pmid = {28391449}, issn = {1432-1262}, mesh = {Anal Canal/physiopathology ; Defecation ; Fecal Incontinence/therapy ; Female ; Humans ; Male ; Middle Aged ; Quality of Life ; Rectum/*physiopathology ; Tibial Nerve/*physiopathology ; *Transcutaneous Electric Nerve Stimulation/adverse effects ; Treatment Outcome ; }, abstract = {PURPOSE: Percutaneous tibial nerve stimulation (pTNS) was originally developed to treat urinary incontinence. Recently, some case series have also documented its success in the treatment of fecal incontinence. Nevertheless, the mechanism underlying this effect remains unknown but may be related to changes in rectal capacity. The aim of this study was to investigate the success of pTNS for the treatment of fecal urge incontinence and assess the influence of rectal capacity on treatment efficacy.<br><br>METHODS: All patients undergoing pTNS for fecal incontinence between July 2009 and March 2014 were enrolled in a prospective, observational study consisting of a therapeutic regimen that lasted 9&#xa0;months. Therapy success was defined as a reduction in the CCI (Cleveland Clinic incontinence) score of &#x2265;50% and patient-reported success. Furthermore, quality of life (Rockwood's scale) and changes in anorectal physiology were recorded.<br><br>RESULTS: Fifty-seven patients with fecal urge incontinence were eligible, nine of whom were excluded. The success rate was 72.5%. Incontinence events and urge symptoms were significantly reduced after 3&#xa0;months and at the end of therapy. The median CCI score decreased from 12 to 4 (P&#xa0;<&#xa0;0.0001), and the quality of life was significantly improved. However, rectal capacity was not significantly related to treatment success before or after therapy. No adverse events were observed.<br><br>CONCLUSIONS: These results demonstrate that pTNS can improve the symptoms and quality of life of patients with fecal urge incontinence. However, the study fails to demonstrate a correlation between treatment success and changes in rectal capacity.}, }
@article {pmid28390576, year = {2017}, author = {Buttó, LF and Haller, D}, title = {Functional relevance of microbiome signatures: The correlation era requires tools for consolidation.}, journal = {The Journal of allergy and clinical immunology}, volume = {139}, number = {4}, pages = {1092-1098}, doi = {10.1016/j.jaci.2017.02.010}, pmid = {28390576}, issn = {1097-6825}, mesh = {Animals ; Gastrointestinal Microbiome/*genetics ; Humans ; Metagenome/*genetics ; Metagenomics/*methods/*standards/trends ; Models, Biological ; }, abstract = {Compelling research over the past decade identified a fundamental role of the intestinal microbiome on human health. Compositional and functional changes of this microbial ecosystem are correlated with a variety of human pathologies. Metagenomic resolution and bioinformatic tools considerably improved, allowing even strain-level analysis. However, the search for microbial risk patterns in human cohorts is often confounded by environmental factors (eg, medication) and host status (eg, disease relapse), questioning the prognostic and therapeutic value of the currently available information. In addition to a better stratification of human phenotypes, the implementation of standardized protocols for sampling and analysis is needed to improve the reproducibility and comparability of microbiome signatures at a meaningful taxonomic resolution. At the level of mechanistic understanding, the molecular integration of pleiotropic signals coming from this complex and dynamically changing ecosystem is one of the biggest challenges in this field. The first successful attempts to apply reverse genetics based on the available metagenomic information yielded identification of small molecules and metabolites with functional relevance for microbe-host interactions. Further expansion on the isolation of bacteria from the "unculturable biomass" will help characterize microbiome signatures in model systems, finally aiming at the development of clinically relevant synthetic consortia with safe and functionally well-defined strains. In conclusion and beyond reasonable enthusiasm, the mechanistic implementation and clinical relevance of microbiome alterations on disease susceptibility is still in its infancy, but the integration of all the above-mentioned strategies will help overcome the correlation era in microbiome research and lead to a rational evaluation of clinical strategies relevant for targeted microbial intervention.}, }
@article {pmid28386472, year = {2017}, author = {von Klitzing, E and Öz, F and Ekmekciu, I and Escher, U and Bereswill, S and Heimesaat, MM}, title = {Comprehensive Survey of Intestinal Microbiota Changes in Offspring of Human Microbiota-Associated Mice.}, journal = {European journal of microbiology &amp; immunology}, volume = {7}, number = {1}, pages = {65-75}, pmid = {28386472}, issn = {2062-509X}, abstract = {Secondary abiotic mice generated by broad-spectrum antibiotic treatment provide a valuable tool for association studies with microbiota derived from different vertebrate hosts. We here generated human microbiota-associated (hma) mice by human fecal microbiota transplantation of secondary abiotic mice and performed a comprehensive survey of the intestinal microbiota dynamics in offspring of hma mice over 18 weeks following weaning as compared to their mothers applying both cultural and molecular methods. Mice were maintained under standard hygienic conditions with open cages, handled under aseptic conditions, and fed autoclaved chow and water. Within 1 week post weaning, fecal loads of commensal enterobacteria and enterococci had decreased, whereas obligate anaerobic bacteria such as Bacteroides/Prevotella species and clostridia were stably colonizing the intestines of hma offspring at high loads. Lactobacilli numbers were successively increasing until 18 weeks post weaning in both hma offspring and mothers, whereas by then, bifidobacteria were virtually undetectable in the former only. Interestingly, fecal lactobacilli and bifidobacteria were higher in mothers as compared to their offspring at 5 and 18 weeks post weaning. We conclude that the intestinal microbiota composition changes in offspring of hma mice, but also their mothers over time particularly affecting aerobic and microaerobic species.}, }
@article {pmid28381525, year = {2018}, author = {Cammarota, G and Ianiro, G and Gasbarrini, A and , }, title = {Faecal microbiota transplantation in clinical practice.}, journal = {Gut}, volume = {67}, number = {1}, pages = {196-197}, doi = {10.1136/gutjnl-2017-314049}, pmid = {28381525}, issn = {1468-3288}, mesh = {Clostridioides difficile ; *Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid28376573, year = {2017}, author = {Sidhu, M and van der Poorten, D}, title = {The gut microbiome.}, journal = {Australian family physician}, volume = {46}, number = {4}, pages = {206-211}, pmid = {28376573}, issn = {0300-8495}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Clostridioides difficile/pathogenicity ; Dysbiosis/*physiopathology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/immunology/*physiology ; Humans ; Inflammatory Bowel Diseases/physiopathology ; Irritable Bowel Syndrome/physiopathology ; Non-alcoholic Fatty Liver Disease/physiopathology ; Probiotics/pharmacology/therapeutic use ; }, abstract = {BACKGROUND: More than a trillion, mostly good, microbes live within our gastrointestinal tract and are responsible for vital metabolic, immune and nutritional functions. Dysbiosis, meaning a maladaptive imbalance of the microbiome, is associated with many common diseases and is a target for therapy.<br><br>OBJECTIVE: This article provides an overview of the gut microbiome in health and disease, highlighting conditions such as Clostridium difficile infection, inflammatory bowel disease, irritable bowel syndrome, obesity and non-alcoholic fatty liver disease, with which dysbiosis is associated. Information about treatments that affect the gut microbiome, including probiotics and faecal microbiota transplant, are discussed.<br><br>DISCUSSION: As our knowledge of the microbiome increases, we are likely to better understand the complex interactions that cause disease, and develop new and more effective treatments for many common conditions.}, }
@article {pmid28372875, year = {2018}, author = {Del Campo-Moreno, R and Alarcón-Cavero, T and D'Auria, G and Delgado-Palacio, S and Ferrer-Martínez, M}, title = {Microbiota and Human Health: characterization techniques and transference.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {36}, number = {4}, pages = {241-245}, doi = {10.1016/j.eimc.2017.02.007}, pmid = {28372875}, issn = {2529-993X}, mesh = {*Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/genetics ; Humans ; Sequence Analysis, DNA ; }, abstract = {The human microbiota comprises all the microorganisms of our body, which can also be categorised as commensals, mutualists and pathogens according to their behaviour. Our knowledge of the human microbiota has considerably increased since the introduction of 16S rRNA next generation sequencing (16S rDNA gene). This technological breakthrough has seen a revolution in the knowledge of the microbiota composition and its implications in human health. This article details the different human bacterial ecosystems and the scientific evidence of their involvement in different diseases. The faecal microbiota transplant procedure, particularly used to treat recurrent diarrhoea caused by Clostridium difficile, and the methodological bases of the new molecular techniques used to characterise microbiota are also described.}, }
@article {pmid28372330, year = {2017}, author = {Jiang, C and Li, G and Huang, P and Liu, Z and Zhao, B}, title = {The Gut Microbiota and Alzheimer's Disease.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {58}, number = {1}, pages = {1-15}, doi = {10.3233/JAD-161141}, pmid = {28372330}, issn = {1875-8908}, mesh = {*Alzheimer Disease/microbiology/pathology/physiopathology ; Brain/*physiopathology ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology/physiopathology ; Humans ; }, abstract = {The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-β peptides (Aβ). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways. Studies in germ-free animals and in animals exposed to pathogenic microbial infections, antibiotics, probiotics, or fecal microbiota transplantation suggest a role for the gut microbiota in host cognition or AD-related pathogenesis. The increased permeability of the gut and blood-brain barrier induced by microbiota dysbiosis may mediate or affect AD pathogenesis and other neurodegenerative disorders, especially those associated with aging. In addition, bacteria populating the gut microbiota can secrete large amounts of amyloids and lipopolysaccharides, which might contribute to the modulation of signaling pathways and the production of proinflammatory cytokines associated with the pathogenesis of AD. Moreover, imbalances in the gut microbiota can induce inflammation that is associated with the pathogenesis of obesity, type 2 diabetes mellitus, and AD. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of the gut microbiota in the development of AD. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for AD.}, }
@article {pmid28371160, year = {2017}, author = {Altomare, DF and Picciariello, A and Ferrara, C and Digennaro, R and Ribas, Y and De Fazio, M}, title = {Short-term outcome of percutaneous tibial nerve stimulation for low anterior resection syndrome: results of a pilot study.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {19}, number = {9}, pages = {851-856}, doi = {10.1111/codi.13669}, pmid = {28371160}, issn = {1463-1318}, mesh = {Aged ; Colectomy/*adverse effects ; Female ; Humans ; Male ; Middle Aged ; Pelvic Floor/innervation/physiopathology ; Pelvic Floor Disorders/etiology/physiopathology/*therapy ; Perineum/physiopathology ; Pilot Projects ; Postoperative Complications/etiology/physiopathology/*therapy ; Severity of Illness Index ; Syndrome ; *Tibial Nerve ; Transcutaneous Electric Nerve Stimulation/*methods ; Treatment Outcome ; }, abstract = {AIM: Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive procedure which has been demonstrated to be effective in faecal/urinary incontinence but has never been tested in low anterior resection syndrome (LARS). The severity of LARS may be evaluated by the LARS score, but rectal cancer treatments may also affect urinary and sexual function, which are not explored by the LARS score. The Three Axial Perineal Evaluation (TAPE) score is a new validated index addressing the overall pelvic floor functions. This study aims to assess the efficacy of PTNS in LARS patients and to evaluate the results by the LARS and TAPE scores.<br><br>METHODS: Twenty-one patients operated on for rectal cancer between 2009 and 2014 complaining of LARS underwent PTNS (12 sessions of 30&#xa0;min each). Six patients reported urinary incontinence and all except two (men) were sexually inactive. The LARS score and the TAPE score questionnaires were administered at baseline and after 6&#xa0;months of follow-up.<br><br>RESULTS: At 6&#xa0;months' follow-up, nine patients reported a significant improvement of faecal incontinence and 3/6 an improvement of urinary incontinence after PTNS. Median LARS score significantly decreased from 32 to 27 (P&#xa0;=&#xa0;0.009), while the median TAPE score improved significantly from 55 to 58 (P&#xa0;=&#xa0;0.004).<br><br>CONCLUSIONS: PTNS may be a further option in the treatment of selected patients with LARS and in addition may improve associated urinary incontinence. The severity of LARS can be detected by the LARS score; however, the adoption of the TAPE score is preferred in the case of concomitant urinary and/or sexual problems not explored by the LARS score.}, }
@article {pmid28369684, year = {2017}, author = {McCoy, KD and Geuking, MB and Ronchi, F}, title = {Gut Microbiome Standardization in Control and Experimental Mice.}, journal = {Current protocols in immunology}, volume = {117}, number = {}, pages = {23.1.1-23.1.13}, doi = {10.1002/cpim.25}, pmid = {28369684}, issn = {1934-368X}, mesh = {Animals ; Fecal Microbiota Transplantation/methods ; Female ; *Gastrointestinal Microbiome ; Genetic Background ; Male ; Mice ; Mice, Transgenic ; Models, Animal ; Phenotype ; *Quality Control ; }, abstract = {Mouse models are used extensively to study human health and to investigate the mechanisms underlying human disease. In the past, most animal studies were performed without taking into consideration the impact of the microbiota. However, the microbiota that colonizes all body surfaces, including the gastrointestinal tract, respiratory tract, genitourinary tract, and skin, heavily impacts nearly every aspect of host physiology. When performing studies utilizing mouse models it is critical to understand that the microbiome is heavily impacted by environmental factors, including (but not limited to) food, bedding, caging, and temperature. In addition, stochastic changes in the microbiota can occur over time that also play a role in shaping microbial composition. These factors lead to massive variability in the composition of the microbiota between animal facilities and research institutions, and even within a single facility. Lack of experimental reproducibility between research groups has highlighted the necessity for rigorously controlled experimental designs in order to standardize the microbiota between control and experimental animals. Well controlled experiments are mandatory in order to reduce variability and allow correct interpretation of experimental results, not just of host-microbiome studies but of all mouse models of human disease. The protocols presented are aimed to design experiments that control the microbiota composition between different genetic strains of experimental mice within an animal unit. © 2017 by John Wiley &amp; Sons, Inc.}, }
@article {pmid28369341, year = {2017}, author = {Bilinski, J and Grzesiowski, P and Sorensen, N and Madry, K and Muszynski, J and Robak, K and Wroblewska, M and Dzieciatkowski, T and Dulny, G and Dwilewicz-Trojaczek, J and Wiktor-Jedrzejczak, W and Basak, GW}, title = {Fecal Microbiota Transplantation in Patients With Blood Disorders Inhibits Gut Colonization With Antibiotic-Resistant Bacteria: Results of a Prospective, Single-Center Study.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {3}, pages = {364-370}, doi = {10.1093/cid/cix252}, pmid = {28369341}, issn = {1537-6591}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Drug Resistance, Bacterial ; *Fecal Microbiota Transplantation/adverse effects/statistics &amp; numerical data ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Hematologic Diseases/*therapy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Patients with blood disorders colonized with antibiotic-resistant bacteria (ARB) are prone to systemic infections that are difficult to treat. Reintroduction of commensal bacteria in a murine model of enterococcal colonization of the gut can lead to eradication of enterococci. We hypothesized that fecal microbiota transplantation (FMT) could be used to eradicate ARB in humans.<br><br>METHODS: Participants colonized with ARB were treated with intraduodenal FMT according to a prospective protocol (NCT02461199). The primary endpoint was complete ARB decolonization at 1 month after FMT. Secondary endpoints included safety assessment and partial ARB decolonization. Microbiome sequencing was performed to investigate the influence of microbial composition of the transplanted material on the outcome of FMT.<br><br>RESULTS: Twenty-five FMTs were performed in 20 participants (including 40% who had neutropenia) who were colonized by a median of 2 (range, 1-4) strains of ARB. The primary endpoint was reached in 15/25 (60%) of the FMTs and more frequently in cases in which there was no periprocedural use of antibiotics (79% vs 36%, P < .05). Among participants, 15/20 (75%) experienced complete ARB decolonization. There were no severe adverse events, and partial ARB decolonization was observed in 20/25 (80%) of the FMTs. The microbiota composition analysis revealed higher abundance of Barnesiella spp., Bacteroides, and Butyricimonas and greater bacterial richness in the fecal material, resulting in eradication of Klebsiella pneumoniae compared with nonresponders.<br><br>CONCLUSIONS: FMT in patients with blood disorders is safe and promotes eradication of ARB from the gastrointestinal tract.<br><br>CLINICAL TRIALS REGISTRATION: NCT02461199.}, }
@article {pmid28362138, year = {2017}, author = {Rasti, S and Hassanzadeh, M and Hooshyar, H and Momen-Heravi, M and Mousavi, SGA and Abdoli, A}, title = {Intestinal parasitic infections in different groups of immunocompromised patients in Kashan and Qom cities, central Iran.}, journal = {Scandinavian journal of gastroenterology}, volume = {52}, number = {6-7}, pages = {738-741}, doi = {10.1080/00365521.2017.1308547}, pmid = {28362138}, issn = {1502-7708}, mesh = {Adult ; Blastocystis hominis/*isolation &amp; purification ; Case-Control Studies ; Cities ; Cross-Sectional Studies ; Feces/parasitology ; Female ; Giardia lamblia/*isolation &amp; purification ; HIV Infections/*complications/parasitology ; Humans ; *Immunocompromised Host ; Intestinal Diseases, Parasitic/*epidemiology ; Iran/epidemiology ; Kidney Transplantation ; Male ; Middle Aged ; Neoplasms/*complications/parasitology ; Renal Dialysis ; Young Adult ; }, abstract = {INTRODUCTION: Intestinal parasitic infections (IPIs) are important causes of morbidity and mortality in patients with immunocompromising conditions.<br><br>OBJECTIVE: The aim of this study was to determine the prevalence of IPIs in different groups of immunocompromised patients, including hemodialysis patients (HD), renal transplant recipients (RTR), cancer and HIV/AIDS patients in comparison with healthy individuals in two central cities of Iran (Kashan and Qom).<br><br>METHODS: In this case-control study, the stool samples of 135&#x2009;HD, 50 RTR, 60 cancer patients, 20 HIV/AIDS patients and 120 healthy subjects were tested using direct-smear, formol-ether concentration, Ziehl-Neelsen staining and Agar plate method.<br><br>RESULTS: The overall infection rate was 11.7% (31/265) in patient groups and 0% (0/120) in the control group. The frequency of parasites was 25% in HIV/AIDS patients, 11.9% (16/135) in HD, 12.0% (6/50) in RTR and 6.7% (4/60) in cancer patients. Blastocystis hominis (4.2%) and Giardia lamblia (3.0%) were the most prevalent parasites in patient groups. The infection rate was significantly higher in male (17.6%) than female (5.4%) patients (p&#x2009;=&#x2009;.002), but no statistically significant association was observed according to the age and educational levels.<br><br>CONCLUSIONS: This study showed a high prevalence of IPIs in immunocompromised patients. The results of this study suggest that periodic stool examinations for screening of IPIs should be included as a part of routine medical care in these patients.}, }
@article {pmid28357349, year = {2016}, author = {Liu, S and Weiner, HL}, title = {Control of the gut microbiome by fecal microRNA.}, journal = {Microbial cell (Graz, Austria)}, volume = {3}, number = {4}, pages = {176-177}, doi = {10.15698/mic2016.04.492}, pmid = {28357349}, issn = {2311-2638}, support = {R01 NS087226/NS/NINDS NIH HHS/United States ; }, abstract = {Since their discovery in the early 90s, microRNAs (miRNAs), small non-coding RNAs, have mainly been associated with posttranscriptional regulation of gene expression on a cell-autonomous level. Recent evidence has extended this role by adding inter-species communication to the manifold functional range. In our latest study [Liu S, et al., 2016, Cell Host &amp; Microbe], we identified miRNAs in gut lumen and feces of both mice and humans. We found that intestinal epithelial cells (IEC) and Hopx+ cells were the two main sources of fecal miRNA. Deficiency of IEC-miRNA resulted in gut dysbiosis and WT fecal miRNA transplantation restored the gut microbiota. We investigated potential mechanisms for this effect and found that miRNAs were able to regulate the gut microbiome. By culturing bacteria with miRNAs, we found that host miRNAs were able to enter bacteria, specifically regulate bacterial gene transcripts and affect bacterial growth. Oral administration of synthetic miRNA mimics affected specific bacteria in the gut. Our findings describe a previously unknown pathway by which the gut microbiome is regulated by the host and raises the possibility that miRNAs may be used therapeutically to manipulate the microbiome for the treatment of disease.}, }
@article {pmid28352104, year = {2018}, author = {Su, C and Su, L and Li, Y and Long, SR and Chang, J and Zhang, W and Walker, WA and Xavier, RJ and Cherayil, BJ and Shi, HN}, title = {Helminth-induced alterations of the gut microbiota exacerbate bacterial colitis.}, journal = {Mucosal immunology}, volume = {11}, number = {1}, pages = {144-157}, pmid = {28352104}, issn = {1935-3456}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 AI089700/AI/NIAID NIH HHS/United States ; R01 DK082427/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacterial Load ; Citrobacter rodentium/*physiology ; Colitis/*immunology/microbiology/parasitology ; Colon/microbiology/parasitology/*pathology ; Disease Progression ; Enterobacteriaceae Infections/*immunology ; Feces/microbiology ; Female ; Immunomodulation ; Interleukin-10/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Microbiota/*immunology ; Nematospiroides dubius/*immunology ; STAT6 Transcription Factor/genetics/metabolism ; Strongylida Infections/*immunology ; T-Lymphocytes, Regulatory/*immunology ; Th2 Cells/*immunology ; }, abstract = {Infection with the intestinal helminth parasite Heligmosomoides polygyrus exacerbates the colitis caused by the bacterial enteropathogen Citrobacter rodentium. To clarify the underlying mechanism, we analyzed fecal microbiota composition of control and helminth-infected mice and evaluated the functional role of compositional differences by microbiota transplantation experiments. Our results showed that infection of Balb/c mice with H. polygyrus resulted in significant changes in the composition of the gut microbiota, characterized by a marked increase in the abundance of Bacteroidetes and decreases in Firmicutes and Lactobacillales. Recipients of the gut microbiota from helminth-infected wide-type, but not STAT6-deficient, Balb/c donors had increased fecal pathogen shedding and significant worsening of Citrobacter-induced colitis compared to recipients of microbiota from control donors. Recipients of helminth-altered microbiota also displayed increased regulatory T cells and IL-10 expression. Depletion of CD4[+]CD25[+] T cells and neutralization of IL-10 in recipients of helminth-altered microbiota led to reduced stool C. rodentium numbers and attenuated colitis. These results indicate that alteration of the gut microbiota is a significant contributor to the H. polygyrus-induced exacerbation of C. rodentium colitis. The helminth-induced alteration of the microbiota is Th2-dependent and acts by promoting regulatory T cells that suppress protective responses to bacterial enteropathogens.}, }
@article {pmid28348415, year = {2017}, author = {Ge, X and Zhao, W and Ding, C and Tian, H and Xu, L and Wang, H and Ni, L and Jiang, J and Gong, J and Zhu, W and Zhu, M and Li, N}, title = {Potential role of fecal microbiota from patients with slow transit constipation in the regulation of gastrointestinal motility.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {441}, pmid = {28348415}, issn = {2045-2322}, mesh = {Animals ; Constipation/*microbiology/*physiopathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Gastrointestinal Motility ; Humans ; Mice ; *Microbiota ; }, abstract = {The gut microbiota is involved in various physiological functions, and disturbances in the host-microbiome have been proven to contribute to the dysfunction of gut; however, whether microbiota participates in the pathogenesis of constipation remains unclear. In this study, we extracted and analyzed microbiota in feces from constipated donors who had undergone effective therapy with fecal microbiota transplantation, transplanted microbiota into pseudo-germ-free mice, and measured gut motility. These mice presented with lower pellet frequency and water percentage, smaller pellet size, delayed gastrointestinal transit time, and weaker spontaneous contractions of colonic smooth muscle. To determine the mechanism underlying delayed gut motility, microbial metabolites were measured. Short chain fatty acids and secondary bile acids were decreased in mice receiving microbiota from constipated donors. Moreover, the compositional changes of gut microbiota in constipated patients were identified, including the operational taxonomic unit, and the species richness and α diversity were much greater than those in healthy volunteers. These findings suggest that alterations of the microbiome might affect gut motility via altered microbial-derived metabolites in the development of constipation, and the restoration of disturbed microbiota might improve the clinical phenotype. This study indicates that regulating the intestinal environment may be a novel therapy strategy for constipation.}, }
@article {pmid28347713, year = {2017}, author = {Srinivasan, I and Tang, SJ and Sones, JQ}, title = {Fecal microbial transplantation.}, journal = {Gastrointestinal endoscopy}, volume = {85}, number = {5}, pages = {1107-1108}, doi = {10.1016/j.gie.2017.03.1520}, pmid = {28347713}, issn = {1097-6779}, mesh = {Endoscopy, Gastrointestinal ; *Fecal Microbiota Transplantation ; Humans ; *Specimen Handling ; }, }
@article {pmid28346928, year = {2017}, author = {Shen, TD}, title = {Diet and Gut Microbiota in Health and Disease.}, journal = {Nestle Nutrition Institute workshop series}, volume = {88}, number = {}, pages = {117-126}, doi = {10.1159/000455220}, pmid = {28346928}, issn = {1664-2155}, mesh = {Animals ; Bacteria/metabolism ; Choline/metabolism ; *Diet ; Dietary Carbohydrates/metabolism ; Dysbiosis/complications/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; *Health Status ; Humans ; Inflammatory Bowel Diseases/microbiology/prevention &amp; control ; Methylamines/metabolism ; Renal Insufficiency, Chronic/microbiology ; }, abstract = {Gut microbiota plays an important role in host health maintenance and disease pathogenesis. The development of a stable and diverse gut microbiota is essential to various host physiologic functions such as immunoregulation, pathogen prevention, energy harvest, and metabolism. At the same time, a dysbiotic gut microbiota associated with disease is altered in structure and function, and often characterized by a decrease in species richness and proliferation of pathogenic bacterial taxa. As a shared substrate between the host and the gut microbiota, diet significantly impacts the health and disease states of the host both directly and through gut microbial metabolite production. This is demonstrated in the examples of short-chain fatty acid and trimethylamine production via bacterial metabolism of dietary complex carbohydrates and choline, respectively. In disorders related to mucosal immune dysregulation such as inflammatory bowel disease, the dysbiotic gut microbiota and diet contribute to its pathogenesis. Reversal of dysbiosis through fecal microbiota transplantation and dietary interventions may thus represent important strategies to modify the gut microbiota and its metabolite production for health maintenance as well as disease prevention and management.}, }
@article {pmid28346923, year = {2017}, author = {Martin, CR and Mayer, EA}, title = {Gut-Brain Axis and Behavior.}, journal = {Nestle Nutrition Institute workshop series}, volume = {88}, number = {}, pages = {45-53}, pmid = {28346923}, issn = {1664-2155}, support = {P50 DK064539/DK/NIDDK NIH HHS/United States ; R01 DK048351/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Autistic Disorder/microbiology ; Behavior/*physiology ; Brain/*physiology ; Depression/microbiology ; Dysbiosis/psychology ; Fecal Microbiota Transplantation ; Feeding Behavior ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*physiology ; Humans ; Irritable Bowel Syndrome/microbiology ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {In the last 5 years, interest in the interactions among the gut microbiome, brain, and behavior has exploded. Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food intake. Limited, but growing, clinical evidence comes primarily from associations of gut microbial composition and function to behavioral and clinical features and brain structure and function. Converging evidence suggests that the brain and the gut microbiota are in bidirectional communication. Observed dysbiotic states in depression, chronic stress, and autism may reflect altered brain signaling to the gut, while altered gut microbial signaling to the brain may play a role in reinforcing brain alterations. On the other hand, primary dysbiotic states due to Western diets may signal to the brain, altering ingestive behavior. While studies performed in patients with depression and rodent models generated by fecal microbial transfer from such patients suggest causation, evidence for an influence of acute gut microbial alterations on human behavioral and clinical parameters is lacking. Only recently has an open-label microbial transfer therapy in children with autism tentatively validated the gut microbiota as a therapeutic target. The translational potential of preclinical findings remains unclear without further clinical investigation.}, }
@article {pmid28345530, year = {2017}, author = {Juszczuk, K and Grudlewska, K and Mikucka, A and Gospodarek, E}, title = {Fecal microbiota transplantation - methods of treatment of recurrent Clostridium difficile infections and other diseases.}, journal = {Postepy higieny i medycyny doswiadczalnej (Online)}, volume = {71}, number = {0}, pages = {220-226}, doi = {10.5604/01.3001.0010.3807}, pmid = {28345530}, issn = {1732-2693}, mesh = {*Clostridioides difficile ; Clostridium Infections/*microbiology/therapy ; Colitis, Ulcerative/therapy ; Crohn Disease/therapy ; Diarrhea/therapy ; Fecal Microbiota Transplantation/methods ; Feces/*microbiology ; Humans ; Intention to Treat Analysis ; Irritable Bowel Syndrome/therapy ; *Microbiota ; Treatment Outcome ; }, abstract = {Clostridium difficile is a serious epidemiological problem and particularly dangerous microorganism causing hospital infections. Currently, the treatment of C. difficile infections is the use of metronidazole or vancomycin. However, in some patients, recurrent infection difficult to treat occurs. Fecal microbiota transplantation (FMT) is a new method used to treat the recurrent CDI. FMT consists in the infusion of the fecal suspension from a healthy donor into the gastrointestinal tract of a patient with CDI to restore the natural intestinal microflora. FMT is safe and effective treatment of recurrent CDI. FMT is extensively described around the world, but to date only two randomized studies confirming the effectiveness of FMT have been conducted. This method was also applied in the treatment of diseases such as pseudomembranous colitis, ulcerative colitis, Crohn's disease and irritable bowel syndrome. The review describes the procedure for FMT and the current state of knowledge about the effectiveness of FMT in the treatment of recurrent CDI.}, }
@article {pmid28339993, year = {2017}, author = {Floege, J and Covic, AC and Ketteler, M and Mann, J and Rastogi, A and Spinowitz, B and Rakov, V and Lisk, LJ and Sprague, SM}, title = {One-year efficacy and safety of the iron-based phosphate binder sucroferric oxyhydroxide in patients on peritoneal dialysis.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {32}, number = {11}, pages = {1918-1926}, doi = {10.1093/ndt/gfw460}, pmid = {28339993}, issn = {1460-2385}, mesh = {Adult ; Aged ; Combined Modality Therapy ; Drug Combinations ; Female ; Ferric Compounds/adverse effects/*therapeutic use ; Humans ; Hyperphosphatemia/blood/*drug therapy/etiology ; Male ; Medication Adherence ; Middle Aged ; Peritoneal Dialysis ; Phosphates/blood ; Sucrose/adverse effects/*therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Sucroferric oxyhydroxide is a noncalcium, iron-based phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with sevelamer carbonate (sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and sevelamer in the peritoneal dialysis (PD) patient population.<br><br>METHODS: The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1.0-3.0&#x2009;g/day) with sevelamer (2.4-14.4&#x2009;g/day) in dialysis patients over 52 weeks in total.<br><br>RESULTS: In the overall study, 84/1055 (8.1%) patients received PD and were eligible for efficacy analysis (sucroferric oxyhydroxide, n&#x2009;=&#x2009;56; sevelamer, n&#x2009;=&#x2009;28). The two groups were broadly comparable to each other and to the overall study population. Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 (mean change from baseline -&#x2009;0.6&#x2009;mmol/L). Over 52 weeks, sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as sevelamer; 62.5% and 64.3% of patients, respectively, were below the Kidney Disease Outcomes Quality Initiative target range (&#x2264;1.78&#x2009;mmol/L). This was achieved with a lower pill burden (3.4&#x2009;&#xb1;&#x2009;1.3 versus 8.1&#x2009;&#xb1;&#x2009;3.7 tablets/day) with sucroferric oxyhydroxide compared with sevelamer. Treatment adherence rates were 91.2% with sucroferric oxyhydroxide and 79.3% with sevelamer. The proportion of patients reporting at least one treatment-emergent adverse event was 86.0% with sucroferric oxyhydroxide and 93.1% with sevelamer. The most common adverse events with both treatments were gastrointestinal: diarrhea and discolored feces with sucroferric oxyhydroxide and nausea, vomiting and constipation with sevelamer.<br><br>CONCLUSIONS: Sucroferric oxyhydroxide is noninferior to sevelamer for controlling serum phosphorus in patients undergoing PD, while providing a relatively low pill burden and a high rate of adherence.}, }
@article {pmid28336719, year = {2017}, author = {Carlos, CA and McCulloch, CE and Hsu, CY and Grimes, B and Pavkov, ME and Burrows, NR and Shahinian, VB and Saran, R and Powe, NR and Johansen, KL and , }, title = {Colon Cancer Screening among Patients Receiving Dialysis in the United States: Are We Choosing Wisely?.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {28}, number = {8}, pages = {2521-2528}, pmid = {28336719}, issn = {1533-3450}, support = {K24 DK092291/DK/NIDDK NIH HHS/United States ; U58 DP003839/DP/NCCDPHP CDC HHS/United States ; UL1 TR000004/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; Cohort Studies ; Colonic Neoplasms/complications/diagnosis ; Colorectal Neoplasms/complications/*diagnosis ; Early Detection of Cancer/*statistics &amp; numerical data ; Female ; Humans ; Kidney Failure, Chronic/complications/therapy ; Kidney Transplantation ; Male ; Middle Aged ; *Renal Dialysis ; United States ; }, abstract = {The American Society of Nephrology recommends against routine cancer screening among asymptomatic patients receiving maintenance dialysis on the basis of limited survival benefit. To determine the frequency of colorectal cancer screening among patients on dialysis and the extent to which screening tests were targeted toward patients at lower risk of death and higher likelihood of receiving a kidney transplant, we performed a cohort study of 469,574 Medicare beneficiaries ages ≥50 years old who received dialysis between January 1, 2007 and September 30, 2012. We examined colorectal cancer screening tests according to quartiles of risk of mortality and kidney transplant on the basis of multivariable Cox modeling. Over a median follow-up of 1.5 years, 11.6% of patients received a colon cancer screening test (57.9 tests per 1000 person-years). Incidence rates of colonoscopy, flexible sigmoidoscopy, and fecal occult blood test were 27.9, 0.6, and 29.5 per 1000 person-years, respectively. Patients in the lowest quartile of mortality risk were more likely to be screened than those in the highest quartile (hazard ratio, 1.53; 95% confidence interval, 1.49 to 1.57; 65.1 versus 46.4 tests per 1000 person-years, respectively), amounting to a 33% higher rate of testing. Additionally, compared with patients least likely to receive a transplant, patients most likely to receive a transplant were more likely to be screened (hazard ratio, 1.68; 95% confidence interval, 1.64 to 1.73). Colon cancer screening is being targeted toward patients on dialysis at lowest risk of mortality and highest likelihood of transplantation, but absolute rates are high, suggesting overscreening.}, }
@article {pmid28333760, year = {2017}, author = {Wurm, P and Spindelboeck, W and Krause, R and Plank, J and Fuchs, G and Bashir, M and Petritsch, W and Halwachs, B and Langner, C and Högenauer, C and Gorkiewicz, G}, title = {Antibiotic-Associated Apoptotic Enterocolitis in the Absence of a Defined Pathogen: The Role of Intestinal Microbiota Depletion.}, journal = {Critical care medicine}, volume = {45}, number = {6}, pages = {e600-e606}, pmid = {28333760}, issn = {1530-0293}, support = {W 1241/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/*adverse effects ; Enterocolitis/*chemically induced/*microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Male ; Middle Aged ; }, abstract = {OBJECTIVE: Antibiotic therapy is a major risk factor for the development of diarrhea and colitis with varying severity. Often the origin of antibiotic-associated gastrointestinal deterioration remains elusive and no specific infectious agents could be discerned.<br><br>PATIENTS: We represent three cases of intractable high-volume diarrhea associated with combined antibiotic and steroid therapy in critically ill patients not fitting into established disease entities. Cases presented with severe apoptotic enterocolitis resembling acute intestinal graft-versus-host-disease. Microbiologic workup precluded known enteropathogens, but microbiota analysis revealed a severely depleted gut microbiota with concomitant opportunistic pathogen overgrowth.<br><br>INTERVENTIONS: Fecal microbiota transplantation, performed in one patient, was associated with correction of dysbiosis, rapid clinical improvement, and healing of enterocolitis.<br><br>CONCLUSIONS: Our series represents a severe form of antibiotic-associated colitis in critically ill patients signified by microbiota depletion, and reestablishment of a physiologic gastrointestinal microbiota might be beneficial for this condition.}, }
@article {pmid28331803, year = {2017}, author = {Coffman, K and Chen, XJ and Okamura, C and Louie, E}, title = {IVIG - A cure to severe refractory NAP-1 Clostridium difficile colitis? A case of successful treatment of severe infection, which failed standard therapy including fecal microbiota transplants and fidaxomicin.}, journal = {IDCases}, volume = {8}, number = {}, pages = {27-28}, pmid = {28331803}, issn = {2214-2509}, abstract = {The mainstay treatment of Clostridium difficile infections (CDI) is antimicrobials with growing support for fecal microbiota transplants. We report the first case of an elderly man with severe refractory NAP-1 pseudomembranous CDI who failed all medical therapy and two fecal transplants with response only seen after administration of intravenous immunoglobulin.}, }
@article {pmid28328941, year = {2017}, author = {Gardinali, NR and Guimarães, JR and Melgaço, JG and Kevorkian, YB and Bottino, FO and Vieira, YR and da Silva, AC and Pinto, DP and da Fonseca, LB and Vilhena, LS and Uiechi, E and da Silva, MC and Moran, J and Marchevsky, RS and Cruz, OG and Otonel, RA and Alfieri, AA and de Oliveira, JM and Gaspar, AM and Pinto, MA}, title = {Cynomolgus monkeys are successfully and persistently infected with hepatitis E virus genotype 3 (HEV-3) after long-term immunosuppressive therapy.}, journal = {PloS one}, volume = {12}, number = {3}, pages = {e0174070}, pmid = {28328941}, issn = {1932-6203}, mesh = {Animals ; Brazil ; Female ; Genotype ; Hepatitis Antibodies/immunology ; Hepatitis E/immunology/virology ; Hepatitis E virus/genetics/immunology/*pathogenicity ; Immunosuppression Therapy/methods ; Immunosuppressive Agents/*immunology ; Liver/immunology/virology ; Liver Cirrhosis/immunology/virology ; Liver Function Tests/methods ; Macaca fascicularis/*immunology/*virology ; Male ; RNA, Viral/genetics ; Virus Shedding/immunology ; }, abstract = {Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs. HEV infected monkeys were followed up during 160 days post infection (dpi) by clinical signs; virological, biochemical and haematological parameters; and liver histopathology. The tacrolimus blood levels were monitored throughout the experiment. Immunosuppression was confirmed by clinical and laboratorial findings, such as: moderate weight loss, alopecia, and herpes virus opportunistic infection. In this study, chronic HEV infection was characterized by the mild increase of liver enzymes serum levels; persistent RNA viremia and viral faecal shedding; and liver histopathology. Three out of four immunosuppressed monkeys showed recurrent HEV RNA detection in liver samples, evident hepatocellular ballooning degeneration, mild to severe macro and microvesicular steatosis (zone 1), scattered hepatocellular apoptosis, and lobular focal inflammation. At 69 dpi, liver biopsies of all infected monkeys revealed evident ballooning degeneration (zone 3), discrete hepatocellular apoptosis, and at most mild portal and intra-acinar focal inflammation. At 160 dpi, the three chronically HEV infected monkeys showed microscopic features (piecemeal necrosis) corresponding to chronic hepatitis in absence of fibrosis and cirrhosis in liver parenchyma. Within 4-months follow up, the tacrolimus-immunosuppressed cynomolgus monkeys infected with a Brazilian swine HEV-3 strain exhibited more severe hepatic lesions progressing to chronic hepatitis without liver fibrosis, similarly as shown in tacrolimus-immunosuppressed solid organ transplant (SOT) recipients. The cause-effect relationship between HEV infection and tacrolimus treatment was confirmed in this experiment.}, }
@article {pmid28323128, year = {2017}, author = {Li, X and Li, X and Shang, Q and Gao, Z and Hao, F and Guo, H and Guo, C}, title = {Fecal microbiota transplantation (FMT) could reverse the severity of experimental necrotizing enterocolitis (NEC) via oxidative stress modulation.}, journal = {Free radical biology &amp; medicine}, volume = {108}, number = {}, pages = {32-43}, doi = {10.1016/j.freeradbiomed.2017.03.011}, pmid = {28323128}, issn = {1873-4596}, mesh = {Animals ; Disease Progression ; Enterocolitis, Necrotizing/immunology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Glutaredoxins/genetics/*metabolism ; Humans ; Inflammation/*immunology ; Intestinal Mucosa/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Animal ; Nitric Oxide Synthase Type III/metabolism ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Toll-Like Receptor 4/metabolism ; Toll-Like Receptor 9/metabolism ; Transcytosis ; }, abstract = {Fecal microbiota transplantation (FMT) has been used successfully to treat a variety of gastroenterological diseases. The alterations of microbiota in mouse models of necrotizing enterocolitis (NEC) as well as in patients suggested the possibility of treating NEC with FMT. Here we show that FMT caused an improvement in the histopathology and symptoms of NEC in WT mice, but not Grx1-/- mice. FMT eliminated O2[•]- production and promoted NO production in experimental NEC mice though the modulation of S-glutathionylation of eNOS (eNOS-SSG). FMT decreased the extent of TLR4-mediated proinflammatory signaling though TLR9 in the intestinal mucosa tissue. FMT also suppressed intestinal apoptosis and bacterial translocation across the intestinal barrier, which was accompanied by decreased inflammatory cytokine levels, altered bacterial microbiota, and regulated lymphocyte proportions. FMT is effective in a mouse model of NEC through the modulation of oxidative stress and reduced colon inflammation.}, }
@article {pmid28322704, year = {2017}, author = {Foster, MA and Weil, LM and Jin, S and Johnson, T and Hayden-Mixson, TR and Khudyakov, Y and Annambhotla, PD and Basavaraju, SV and Kamili, S and Ritter, JM and Nelson, N and Mazariegos, G and Green, M and Himes, RW and Kuhar, DT and Kuehnert, MJ and Miller, JA and Wiseman, R and Moorman, AC}, title = {Transmission of Hepatitis A Virus through Combined Liver-Small Intestine-Pancreas Transplantation.}, journal = {Emerging infectious diseases}, volume = {23}, number = {4}, pages = {590-596}, pmid = {28322704}, issn = {1080-6059}, mesh = {Adult ; Child ; Hepatitis A/*transmission/*virology ; Hepatitis A virus/genetics/*physiology ; Humans ; Infectious Disease Transmission, Patient-to-Professional ; Nurses ; Organ Transplantation/*adverse effects ; Transplant Recipients ; }, abstract = {Although transmission of hepatitis A virus (HAV) through blood transfusion has been documented, transmission through organ transplantation has not been reported. In August 2015, state health officials in Texas, USA, were notified of 2 home health nurses with HAV infection whose only common exposure was a child who had undergone multi-visceral organ transplantation 9 months earlier. Specimens from the nurses, organ donor, and all organ recipients were tested and medical records reviewed to determine a possible infection source. Identical HAV RNA sequences were detected from the serum of both nurses and the organ donor, as well as from the multi-visceral organ recipient's serum and feces; this recipient's posttransplant liver and intestine biopsy specimens also had detectable virus. The other organ recipients tested negative for HAV RNA. Vaccination of the donor might have prevented infection in the recipient and subsequent transmission to the healthcare workers.}, }
@article {pmid28320888, year = {2017}, author = {Touw, K and Ringus, DL and Hubert, N and Wang, Y and Leone, VA and Nadimpalli, A and Theriault, BR and Huang, YE and Tune, JD and Herring, PB and Farrugia, G and Kashyap, PC and Antonopoulos, DA and Chang, EB}, title = {Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models.}, journal = {Physiological reports}, volume = {5}, number = {6}, pages = {}, pmid = {28320888}, issn = {2051-817X}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R03 DK111850/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; K08 DK100638/DK/NIDDK NIH HHS/United States ; R01 DK097268/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Constipation/chemically induced/*microbiology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; *Host-Pathogen Interactions ; Humans ; Irritable Bowel Syndrome/*microbiology ; Loperamide ; Male ; Mice ; }, abstract = {Chronic diseases arise when there is mutual reinforcement of pathophysiological processes that cause an aberrant steady state. Such a sequence of events may underlie chronic constipation, which has been associated with dysbiosis of the gut. In this study we hypothesized that assemblage of microbial communities, directed by slow gastrointestinal transit, affects host function in a way that reinforces constipation and further maintains selection on microbial communities. In our study, we used two models - an opioid-induced constipation model in mice, and a humanized mouse model where germ-free mice were colonized with stool from a patient with constipation-predominant irritable bowel syndrome (IBS-C) in humans. We examined the impact of pharmacologically (loperamide)-induced constipation (PIC) and IBS-C on the structural and functional profile of the gut microbiota. Germ-free (GF) mice were colonized with microbiota from PIC donor mice and IBS-C patients to determine how the microbiota affects the host. PIC and IBS-C promoted changes in the gut microbiota, characterized by increased relative abundance of Bacteroides ovatus and Parabacteroides distasonis in both models. PIC mice exhibited decreased luminal concentrations of butyrate in the cecum and altered metabolic profiles of the gut microbiota. Colonization of GF mice with PIC-associated mice cecal or human IBS-C fecal microbiota significantly increased GI transit time when compared to control microbiota recipients. IBS-C-associated gut microbiota also impacted colonic contractile properties. Our findings support the concept that constipation is characterized by disease-associated steady states caused by reinforcement of pathophysiological factors in host-microbe interactions.}, }
@article {pmid28318396, year = {2017}, author = {Hoffmann, DE and Palumbo, FB and Ravel, J and Rowthorn, V and von Rosenvinge, E}, title = {A proposed definition of microbiota transplantation for regulatory purposes.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {208-213}, pmid = {28318396}, issn = {1949-0984}, support = {R21 AI119633/AI/NIAID NIH HHS/United States ; }, mesh = {Clostridium Infections/therapy ; Fecal Microbiota Transplantation/*methods/*standards ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; United States ; United States Food and Drug Administration ; }, abstract = {The advent of fecal microbiota transplantation (FMT) and the prospect of other types of microbiota transplants (MT), e.g. vaginal, skin, oral and nasal, are challenging regulatory agencies. Although FDA is regulating FMT (as a biologic), there is currently no widely accepted or agreed upon scientific or legal definition of FMT or MT. The authors report on discussions regarding a definition of MT that took place among a working group of stakeholders convened under a National Institutes for Allergies and Infectious Diseases grant to address the regulation of MT. In arriving at a definition, the group considered the 1) nature of the material being transplanted; 2) degree of manipulation of the transferred materials prior to implantation; 3) ability to characterize the transplanted product using external techniques; and 4) origin of the stool product (single vs multiple donors).}, }
@article {pmid28318210, year = {2017}, author = {Shaukat, A and Reinink, AR}, title = {Fecal Microbiota Transplantation in Clostridium difficile Infection: Evidence and Indications.}, journal = {American family physician}, volume = {95}, number = {6}, pages = {351-352}, pmid = {28318210}, issn = {1532-0650}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Humans ; Male ; Microbiota ; United States ; }, }
@article {pmid28315032, year = {2017}, author = {Cohen, NA and Maharshak, N}, title = {Novel Indications for Fecal Microbial Transplantation: Update and Review of the Literature.}, journal = {Digestive diseases and sciences}, volume = {62}, number = {5}, pages = {1131-1145}, pmid = {28315032}, issn = {1573-2568}, mesh = {Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Gastrointestinal Diseases/microbiology/*therapy ; Humans ; }, abstract = {BACKGROUND AND AIMS: Fecal microbial transplantation (FMT) is an established successful treatment modality for recurrent Clostridium difficile infection (CDI). The safety profile and potential therapeutic advantages of FMT for diseases associated with dysbiosis and immune dysfunction have led to many publications, mainly case series, and while many studies and reviews have been published on the use of FMT for inflammatory bowel disease (IBD), its potential use for other disease conditions has not been thoroughly reviewed. The aim of this review was to investigate the evidence surrounding the use of FMT in conditions other than IBD and CDI.<br><br>METHODS: A PubMed search was performed using the terms "Fecal microbiota transplantation" OR "FMT" OR "Bacteriotherapy."<br><br>RESULTS: A total of 26 articles describing the use of FMT in a variety of both intra-and extraintestinal disease conditions including gastrointestinal, hematologic, neurologic, metabolic, infectious, and autoimmune disorders have been included in this review and have demonstrated some positive results. The studies included were case reports, case series, controlled trials, and cohort studies.<br><br>CONCLUSIONS: The findings of these studies demonstrate that FMT, particularly in conditions associated with gastrointestinal dysbiosis, shows promise to provide another effective tool in the therapeutic armament of the practicing physician. FMT was found to be possibly effective in various diseases, mostly associated with enteric dysbiosis or with immune dysfunction. Randomized clinical studies on large populations should be performed to explore the effectiveness of this therapy, and basic research studies should be designed to gain understanding of the mechanisms through which impact these disorders.}, }
@article {pmid28296584, year = {2017}, author = {Peled, JU and Devlin, SM and Staffas, A and Lumish, M and Khanin, R and Littmann, ER and Ling, L and Kosuri, S and Maloy, M and Slingerland, JB and Ahr, KF and Porosnicu Rodriguez, KA and Shono, Y and Slingerland, AE and Docampo, MD and Sung, AD and Weber, D and Alousi, AM and Gyurkocza, B and Ponce, DM and Barker, JN and Perales, MA and Giralt, SA and Taur, Y and Pamer, EG and Jenq, RR and van den Brink, MRM}, title = {Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {35}, number = {15}, pages = {1650-1659}, pmid = {28296584}, issn = {1527-7755}, support = {R01 AI101406/AI/NIAID NIH HHS/United States ; R25 CA020449/CA/NCI NIH HHS/United States ; R01 HL069929/HL/NHLBI NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; T32 CA009207/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; R01 AI080455/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; KL2 TR001115/TR/NCATS NIH HHS/United States ; R01 AI100288/AI/NIAID NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; UL1 TR000457/TR/NCATS NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/metabolism ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Graft vs Host Disease/microbiology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Neoplasms/metabolism/*microbiology/*surgery ; Retrospective Studies ; Transplantation, Homologous ; }, abstract = {Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT. Methods The intestinal microbiota of 541 patients admitted for allo-HCT was profiled by means of 16S ribosomal sequencing of prospectively collected stool samples. We examined the relationship between abundance of microbiota species or groups of related species and relapse/progression of disease during 2 years of follow-up time after allo-HCT by using cause-specific proportional hazards in a retrospective discovery-validation cohort study. Results Higher abundance of a bacterial group composed mostly of Eubacterium limosum in the validation set was associated with a decreased risk of relapse/progression of disease (hazard ratio [HR], 0.82 per 10-fold increase in abundance; 95% CI, 0.71 to 0.95; P = .009). When the patients were categorized according to presence or absence of this bacterial group, presence also was associated with less relapse/progression of disease (HR, 0.52; 95% CI, 0.31 to 0.87; P = .01). The 2-year cumulative incidences of relapse/progression among patients with and without this group of bacteria were 19.8% and 33.8%, respectively. These associations remained significant in multivariable models and were strongest among recipients of T-cell-replete allografts. Conclusion We found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after allo-HCT. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after allo-HCT.}, }
@article {pmid28293937, year = {2017}, author = {Holleran, G and Lopetuso, LR and Ianiro, G and Pecere, S and Pizzoferrato, M and Petito, V and Graziani, C and McNAMARA, D and Gasbarrini, A and Scaldaferri, F}, title = {Gut microbiota and inflammatory bowel disease: so far so gut!.}, journal = {Minerva gastroenterologica e dietologica}, volume = {63}, number = {4}, pages = {373-384}, doi = {10.23736/S1121-421X.17.02386-8}, pmid = {28293937}, issn = {1827-1642}, mesh = {Dysbiosis/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/immunology/*microbiology/*therapy ; Prebiotics/*administration &amp; dosage ; Probiotics/*therapeutic use ; Treatment Outcome ; }, abstract = {Major advances have occurred in the knowledge of the pathogenesis of inflammatory bowel disease (IBD) over the last decade, and perhaps the most major, and clinically advantageous of these advances has been the discovery of the microbiome as a key multifaceted component of inflammation. The gut microbiome is the largest known group of cells in the body, and is now recognized as an organ in its own right. Initial studies looking at a possible role of bacterial manipulation of the immune system in IBD, looked at identifying a specific bacterial species, and were not representative of a feasible model of inflammation in IBD overall. More recently there has been a shift towards the concept of dysbiosis, and the acceptance that a number of bacterial factors interact with the immune system in order for inflammation to occur. In the present review we will focus on past perspective of the role of microbiota in IBD, current evidences about dysbiosis in IBD and also the main therapeutic modalities to affect IBD by affecting gut microbiota: probiotics, prebiotics, fecal microbiota transplantation and emerging dietary intervention.}, }
@article {pmid28293713, year = {2017}, author = {Metafuni, E and Giammarco, S and De Ritis, DG and Rossi, M and De Michele, T and Zuppi, C and Bacigalupo, AP and Sica, S and Chiusolo, P}, title = {Fecal but not serum calprotectin is a potential marker of GVHD after stem cell transplantation.}, journal = {Annals of hematology}, volume = {96}, number = {6}, pages = {929-933}, doi = {10.1007/s00277-017-2974-1}, pmid = {28293713}, issn = {1432-0584}, mesh = {Biomarkers/blood/*metabolism ; Diagnosis, Differential ; Diarrhea/diagnosis/etiology/*metabolism ; Feces/*chemistry ; Graft vs Host Disease/diagnosis/etiology/*metabolism ; Hematopoietic Stem Cell Transplantation/adverse effects/*methods ; Humans ; Leukocyte L1 Antigen Complex/blood/*metabolism ; Retrospective Studies ; Sensitivity and Specificity ; Transplantation, Homologous ; }, abstract = {Gastrointestinal graft-versus-host disease (GvHD) represents a life-threatening complication after stem cell transplantation. Differential diagnosis between gut GvHD and other causes of diarrhea after HSCT is still subjected to endoscopy and histological findings. The research for a reliable biomarker for gut GvHD might allow an early diagnosis of this condition and a consequent prompt treatment that could reduce unfavorable outcomes. Recently, fecal calprotectin was reported as reliable marker of gut involvement. We would evaluate if serum instead of fecal calprotectin could be considered a possible biomarker of gut GvHD. Serum calprotectin was measured in a cohort of 54 patients submitted to allogeneic stem cell transplantation using ELISA assay. For a subset of 21 patients, calprotectin serum levels were compared with fecal calprotectin detection. Contrary to fecal calprotectin, we found only a trend to high level of serum calprotectin for GvHD development and gut involvement, but statistical difference was not reached. Fecal but not serum calprotectin could be considered as possible biomarker for gut GvHD.}, }
@article {pmid28289858, year = {2017}, author = {Barnes, D and Park, KT}, title = {Donor Considerations in Fecal Microbiota Transplantation.}, journal = {Current gastroenterology reports}, volume = {19}, number = {3}, pages = {10}, pmid = {28289858}, issn = {1534-312X}, mesh = {Donor Selection/*methods/trends ; Dysbiosis/therapy ; Enterocolitis, Pseudomembranous/microbiology/therapy ; Fecal Microbiota Transplantation/*methods/trends ; Gastrointestinal Microbiome ; Humans ; Randomized Controlled Trials as Topic ; }, abstract = {PURPOSE OF REVIEW: Tremendous acceleration has been made in understanding the gut microbiota in the past decade and, with it, further understanding of the pathologic role of dysbiosis and the use of fecal microbiota transplantation (FMT) as therapy. FMT has been studied in many disease states including the most common indication of Clostridium difficile infection (CDI), though many questions regarding stool donor selection remain.<br><br>RECENT FINDINGS: Though traditionally, one donor has provided stool for one patient, research is underway to explore many donor selection considerations from the use of pooled donor stool to selection of a high diversity donor. It is well-known that dietary intake shapes the gut microbiota and the potential implications of this on FMT donor selection are being explored. Though further high-quality research is needed, optimizing the fecal microbiota inoculum holds great promise.}, }
@article {pmid28288099, year = {2017}, author = {Chen, L and Wilson, JE and Koenigsknecht, MJ and Chou, WC and Montgomery, SA and Truax, AD and Brickey, WJ and Packey, CD and Maharshak, N and Matsushima, GK and Plevy, SE and Young, VB and Sartor, RB and Ting, JP}, title = {NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth.}, journal = {Nature immunology}, volume = {18}, number = {5}, pages = {541-551}, pmid = {28288099}, issn = {1529-2916}, support = {R01 CA156330/CA/NCI NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; F32 DK088417/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; F32 DK098916/DK/NIDDK NIH HHS/United States ; U19 AI067798/AI/NIAID NIH HHS/United States ; R37 AI029564/AI/NIAID NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; P01 DK094779/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Biodiversity ; Clostridiales/*physiology ; Colitis, Ulcerative/chemically induced/*immunology/microbiology ; Colon/microbiology/*physiology ; Dextran Sulfate ; Feces/microbiology ; Firmicutes/*physiology ; Gene-Environment Interaction ; Humans ; Immunity, Innate/genetics ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Microbiota/genetics/immunology ; RNA, Ribosomal, 16S/*analysis ; Symbiosis ; Twins, Monozygotic ; }, abstract = {Inflammatory bowel diseases involve the dynamic interaction of host genetics, the microbiome and inflammatory responses. Here we found lower expression of NLRP12 (which encodes a negative regulator of innate immunity) in human ulcerative colitis, by comparing monozygotic twins and other patient cohorts. In parallel, Nlrp12 deficiency in mice caused increased basal colonic inflammation, which led to a less-diverse microbiome and loss of protective gut commensal strains (of the family Lachnospiraceae) and a greater abundance of colitogenic strains (of the family Erysipelotrichaceae). Dysbiosis and susceptibility to colitis associated with Nlrp12 deficency were reversed equally by treatment with antibodies targeting inflammatory cytokines and by the administration of beneficial commensal Lachnospiraceae isolates. Fecal transplants from mice reared in specific-pathogen-free conditions into germ-free Nlrp12-deficient mice showed that NLRP12 and the microbiome each contributed to immunological signaling that culminated in colon inflammation. These findings reveal a feed-forward loop in which NLRP12 promotes specific commensals that can reverse gut inflammation, while cytokine blockade during NLRP12 deficiency can reverse dysbiosis.}, }
@article {pmid28286571, year = {2017}, author = {Shivaji, S}, title = {We are not alone: a case for the human microbiome in extra intestinal diseases.}, journal = {Gut pathogens}, volume = {9}, number = {}, pages = {13}, pmid = {28286571}, issn = {1757-4749}, abstract = {BACKGROUND: "Dysbiosis" in the gut microbiome has been implicated in auto-immune diseases, in inflammatory diseases, in some cancers and mental disorders. The challenge is to unravel the cellular and molecular basis of dysbiosis so as to understand the disease manifestation.<br><br>MAIN BODY: Next generation sequencing and genome enabled technologies have led to the establishment of the composition of gut microbiomes and established that "dysbiosis" is the cause of several diseases. In a few cases the cellular and molecular changes accompanying dysbiosis have been investigated and correlated with the disease. Gut microbiome studies have indicated that Christensenella minuta controls obesity in mice, Faecalibacterium prausnitzii protects mice against intestinal inflammation and Akkermansia muciniphila reverses obesity and insulin resistance by secreting endocannabinoids. In mice polysaccharide antigen A on the surface of Bacteroides fragilis, reduces inflammation. Such experiments provide the link between the gut microbiome and human health but implicating dysbiosis with extra-intestinal diseases like arthritis, muscular dystrophy, vaginosis, fibromyalgia, some cancers and mental disorders appears to be more challenging. The relevance of gut microbiome to the eye appears to be very remote. But considering that the eye is the site of inflammatory diseases like uveitis, scleritis, Mooren's corneal ulcer etc. it is possible that these diseases are also influenced by dysbiosis. In mice signals from the gut microbiota activate retina specific T cells that are involved in autoimmune uveitis. Such information would open up new strategies for therapy where the emphasis would be on restoring the diversity in the gut by antibiotic or specific drug use, specific microbe introduction, probiotic use and fecal transplant therapy. The ocular surface microbiome may also be responsible for eye diseases in man but such studies are lacking. Microbiome of the healthy cornea and conjunctiva have been identified. But whether the ocular microbiome exhibits dysbiosis with disease? Whether ocular microbiome is influenced by the gut microbiome? What mediates the cross-talk between the gut and ocular microbiomes? These are questions that need to be addressed to understand idiopathic infections of the eye.<br><br>CONCLUSIONS: Evaluating diseases remote from the gut would unfold the mysteries of the microbiome.}, }
@article {pmid28282270, year = {2017}, author = {Staley, C and Vaughn, BP and Graiziger, CT and Singroy, S and Hamilton, MJ and Yao, D and Chen, C and Khoruts, A and Sadowsky, MJ}, title = {Community dynamics drive punctuated engraftment of the fecal microbiome following transplantation using freeze-dried, encapsulated fecal microbiota.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {276-288}, pmid = {28282270}, issn = {1949-0984}, support = {L30 DK099831/DK/NIDDK NIH HHS/United States ; R21 AI114722/AI/NIAID NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Administration, Oral ; Bacteroidetes/isolation &amp; purification ; Bile Acids and Salts/analysis ; Biodiversity ; Capsules ; Chromatography, Liquid ; Clostridium Infections/therapy ; DNA, Bacterial/genetics ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Firmicutes/isolation &amp; purification ; Follow-Up Studies ; *Freeze Drying ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Mass Spectrometry ; Proteobacteria/isolation &amp; purification ; Recurrence ; Sequence Analysis, DNA ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a highly effective treatment of recurrent and recalcitrant Clostridium difficile infection (rCDI). In a recent study oral-delivery of encapsulated, freeze-dried donor material, resulted in comparable rates of cure to colonoscopic approaches. Here we characterize shifts in the fecal bacterial community structure of patients treated for rCDI using encapsulated donor material. Prior to FMT, patient fecal samples showed declines in diversity and abundance of Firmicutes and Bacteroidetes, with concurrent increases in members of the Proteobacteria, specifically Enterobacteriaceae. Moreover, patients who experienced recurrence of CDI within the 2-month clinical follow-up had greater abundances of Enterobacteriaceae and did not show resolution of dysbioses. Despite resolution of rCDI following oral-administration of encapsulated fecal microbiota, community composition was slow to return to a normal donor-like assemblage. Post-FMT taxa within the Firmicutes showed rapid increases in relative abundance and did not vary significantly over time. Conversely, Bacteroidetes taxa only showed significant increases in abundance after one month post-FMT, corresponding to significant increases in the community attributable to the donors. Changes in the associations among dominant OTUs were observed at days, weeks, and months post-FMT, suggesting shifts in community dynamics may be related to the timing of increases in abundance of specific taxa. Administration of encapsulated, freeze-dried, fecal microbiota to rCDI patients resulted in restoration of bacterial diversity and resolution of dysbiosis. However, shifts in the fecal microbiome were incremental rather than immediate, and may be driven by changes in community dynamics reflecting changes in the host environment.}, }
@article {pmid28280484, year = {2017}, author = {Ericsson, AC and Personett, AR and Turner, G and Dorfmeyer, RA and Franklin, CL}, title = {Variable Colonization after Reciprocal Fecal Microbiota Transfer between Mice with Low and High Richness Microbiota.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {196}, pmid = {28280484}, issn = {1664-302X}, support = {K01 OD019924/OD/NIH HHS/United States ; U42 OD010918/OD/NIH HHS/United States ; }, abstract = {Several associations have been made between characteristics of the resident gut microbiota and human health and disease susceptibility. Animal models provide the means to test these correlations prospectively and evaluate causality. Experimental fecal microbiota transfer (FMT), or the intentional transplantation of gut microbes into recipient mice depleted of their autochthonous microbes with antibiotics, is a commonly used method of testing these relationships. The true completeness of microbial transfer through such procedures is poorly documented in the literature, particularly in the context of reciprocal transfer of microbes between recipient and donor mice harboring microbial populations of differing richness and diversity. Moreover, it is unclear whether the use of frozen fecal contents or cecal contents would confer any difference in the outcomes of transfer. Herein, groups of mice colonized with distinct gut microbiota of differing richness and composition were used in a reciprocal FMT study, with different groups receiving transfer of material prepared from fresh cecal contents, fresh feces, or frozen feces. Targeted 16S rRNA gene amplicon sequencing was used at intervals throughout the study to characterize the microbiota. Notably, despite comparable depletion of the microbiota in recipient mice prior to transfer, donor-specific taxa reliably colonized recipients only when relatively rich donor material was transferred to mice originally colonized with a simpler microbiota. It is unclear whether these differences were due to differences in the endogenous recipient microbiota or host factors induced in early life by microbial factors. These findings are of practical import for researchers using FMT to prospectively assess the influence of the gut microbiota in mouse models, and to those studying host-microbial interactions and their influence on gut barrier function.}, }
@article {pmid28277809, year = {2017}, author = {Garay, RP}, title = {Vaccinating against depression or anxiety: is it plausible?.}, journal = {Expert opinion on biological therapy}, volume = {17}, number = {5}, pages = {525-528}, doi = {10.1080/14712598.2017.1300654}, pmid = {28277809}, issn = {1744-7682}, mesh = {*Anxiety ; *Depression ; Humans ; Microbiota ; }, }
@article {pmid28277472, year = {2017}, author = {Devakumar, H and Chandrasekaran, N and Alas, A and Martin, L and Davila, GW and Hurtado, E}, title = {Transvaginal Repair of Complex Rectovaginal Fistulas Using the Porcine Urinary Bladder Matrix as an Augmenting Graft.}, journal = {Female pelvic medicine &amp; reconstructive surgery}, volume = {23}, number = {3}, pages = {e25-e28}, doi = {10.1097/SPV.0000000000000410}, pmid = {28277472}, issn = {2154-4212}, mesh = {Aged ; Aged, 80 and over ; Animals ; *Bioprosthesis ; Female ; Humans ; Rectovaginal Fistula/etiology/pathology/*surgery ; Rectum/surgery ; Suburethral Slings/*adverse effects ; Surgical Flaps/*transplantation ; Surgical Mesh/*adverse effects ; Swine ; Urinary Bladder/transplantation ; Vagina/surgery ; }, abstract = {BACKGROUND: After the US Food and Drug Administration issued a safety warning concerning vaginal mesh implants in 2008, their use in correction of pelvic floor defects have decreased in the United States (http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm479732.htm). However, we are still treating patients who have had complications associated with their use, rectovaginal fistulas (RVFs) being one of them. Rectovaginal fistulas are considered complex if greater than 2.5 cm, recurrent, associated with inflammatory bowel disease, or if they are proximal in location. Various surgical techniques have been described for treating RVFs. Interposition grafts such as Martius, gracilis, omental J flaps, and rectus abdominis flaps have been used extensively in correcting RVFs (Am J Gastroenterol 2014;109(8):1141-1157). However, these techniques may increase morbidity or have poor cosmesis. Pelvic surgeons have chronicled the use of biologic grafts for fistula repair. Of the various biologic grafts in use, there have been no reports describing the use of porcine urinary bladder matrix (UBM) for fistula repair. We report on 2 cases of large, complex RVFs secondary to mesh erosion, which were effectively treated with transvaginal repair using the UBM.<br><br>CASES: An 80-year-old woman was referred by the colorectal service to our urogynecology service with complaints of rectal bleeding and vaginal spotting secondary to mesh erosion. Surgical history included hysterectomy with mesh augmented posterior repair with synthetic midurethral sling placement in 2002. Examination revealed a 3-cm mesh exposure located in the middle third of the posterior vaginal wall. On rectovaginal examination, a 3-cm full-thickness RVF with through-and-through mesh erosion was noted between the rectum and vagina.A 65-year-old woman presented to our service with complaints of passage of fecal material through the vagina. Surgical history was significant for hysterectomy in 1988 and prolapse repair with anterior and posterior vaginal mesh in 2009. Subsequently in 2011, she had part of the mesh removed because of exposure. Vaginal examination revealed mesh exposure at the right sulcus of the anterior wall consistent with evidence of prior sling and another mesh exposure on the posterior vaginal wall. Rectovaginal examination revealed palpable mesh in the rectovaginal septum with a 3-cm large and complex fistula. Both of our patients underwent transvaginal excision of mesh, RVF repair, and posterior repair with augmentation with UBM. At 6- and 10-month follow-up, they reported complete resolution of their symptoms with no fistula noted on physical examination.<br><br>CONCLUSIONS: Typically, traditional repair with use of muscular advancement flaps is performed for complex RVF closures. Recently, however, various biologic agents have been successfully used to augment RVF repair. In our cases, the use of UBM led to successful follow-up at 6 to 8 months. Despite existing literature, there remains a void in the depth of knowledge regarding the UBM grafts. Larger studies utilizing it for repair of RVFs are warranted to further understand the success and effectiveness of the UBM grafts for RVF repair.}, }
@article {pmid28276816, year = {2017}, author = {Rodriguez, EA and Carey, EJ and Lindor, KD}, title = {Emerging treatments for primary sclerosing cholangitis.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {11}, number = {5}, pages = {451-459}, doi = {10.1080/17474124.2017.1293524}, pmid = {28276816}, issn = {1747-4132}, mesh = {Anti-Bacterial Agents/adverse effects/*therapeutic use ; Cholagogues and Choleretics/adverse effects/*therapeutic use ; Cholangitis, Sclerosing/diagnosis/immunology/microbiology/*therapy ; *Endoscopy, Digestive System/adverse effects ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Liver Transplantation/adverse effects ; Treatment Outcome ; }, abstract = {Primary sclerosing cholangitis (PSC) is a chronic, cholestatic, idiopathic liver disease that can progress to end-stage liver disease, cirrhosis and cholangiocarcinoma. PSC is an uncommon and highly heterogeneous disease, associated with inflammatory bowel disease and a complex pathophysiology. To date, no medical therapies have proved effective. The only available treatment for end-stage PSC is liver transplant, but recurrence is a significant complication. Areas covered: This review will explore previously tested treatments, discuss current treatment strategies and present viewpoints about future emerging therapies in PSC. We searched PubMed using the noted keywords. We included data from full-text articles published in English. Further relevant articles were identified from the reference lists of review articles. Expert commentary: The development of new therapies in PSC has been challenging. However, with greater awareness of the disease nowadays, new insights into the disease may help in the design of future therapeutic agents in PSC and ultimately in effective therapies.}, }
@article {pmid28275312, year = {2017}, author = {Günaltay, S and Rademacher, L and Hultgren Hörnquist, E and Bohr, J}, title = {Clinical and immunologic effects of faecal microbiota transplantation in a patient with collagenous colitis.}, journal = {World journal of gastroenterology}, volume = {23}, number = {7}, pages = {1319-1324}, pmid = {28275312}, issn = {2219-2840}, mesh = {Aged ; Biopsy ; Colitis, Collagenous/immunology/*microbiology/*therapy ; Colitis, Ulcerative/therapy ; Diarrhea ; *Fecal Microbiota Transplantation ; Feces ; Female ; Flow Cytometry ; Humans ; Lymphocytes/*cytology ; Microbiota ; }, abstract = {One to six percent of patients with microscopic colitis are refractory to medical treatment. The effect of faecal microbiota transplantation (FMT) in active collagenous colitis (CC) has, to the best of our knowledge, never been reported before. Here, we report the effect of repeated FMT in a patient with CC. The patient presented with severe symptoms including profuse diarrhea and profound weight loss. Although she responded to budesonide in the beginning, she became gradually refractory to medical treatment, and was therefore treated with FMT. The patient remained in remission for 11 mo after the third faecal transplantation. The immunomodulatory effect of the therapy was evaluated using flow cytometry, which showed alterations in the profile of intraepithelial and lamina propria lymphocyte subsets after the second transplantation. Our observations indicate that FMT can have an effect in CC, which support the hypothesis that luminal factors, influencing the intestinal microbiota, are involved in the pathogenesis of CC.}, }
@article {pmid28274998, year = {2018}, author = {Terveer, EM and van Beurden, YH and Goorhuis, A and Mulder, CJJ and Kuijper, EJ and Keller, JJ and , }, title = {Faecal microbiota transplantation in clinical practice.}, journal = {Gut}, volume = {67}, number = {1}, pages = {196}, doi = {10.1136/gutjnl-2017-313909}, pmid = {28274998}, issn = {1468-3288}, mesh = {*Clostridioides difficile ; Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid28274145, year = {2017}, author = {Péchiné, S and Janoir, C and Collignon, A}, title = {Emerging monoclonal antibodies against Clostridium difficile infection.}, journal = {Expert opinion on biological therapy}, volume = {17}, number = {4}, pages = {415-427}, doi = {10.1080/14712598.2017.1300655}, pmid = {28274145}, issn = {1744-7682}, mesh = {Animals ; Antibodies, Monoclonal/*administration &amp; dosage/immunology ; Bacterial Proteins/administration &amp; dosage/immunology ; *Clostridioides difficile ; Clostridium Infections/diagnosis/*drug therapy/immunology ; Disease Models, Animal ; Drug Delivery Systems/trends ; Humans ; Immunization, Passive/*methods ; Vaccines/administration &amp; dosage/immunology ; }, abstract = {Clostridium difficile infections are characterized by a high recurrence rate despite antibiotic treatments and there is an urgent need to develop new treatments such as fecal transplantation and immonotherapy. Besides active immunotherapy with vaccines, passive immunotherapy has shown promise, especially with monoclonal antibodies. Areas covered: Herein, the authors review the different assays performed with monoclonal antibodies against C. difficile toxins and surface proteins to treat or prevent primary or recurrent episodes of C. difficile infection in animal models and in clinical trials as well. Notably, the authors lay emphasis on the phase III clinical trial (MODIFY II), which allowed bezlotoxumab to be approved by the Food and Drug Administration and the European Medicines Agency. They also review new strategies for producing single domain antibodies and nanobodies against C. difficile and new approaches to deliver them in the digestive tract. Expert opinion: Only two human Mabs against TcdA and TcdB have been tested alone or in combination in clinical trials. However, many animal model studies have provided rationale for the use of Mabs and nanobodies in C. difficile infection and pave the way for further clinical investigation.}, }
@article {pmid28267142, year = {2017}, author = {Moayyedi, P and Jaeschke, R}, title = {Microbiome: fecal transplant in Clostridium difficile and ulcerative colitis. Dr. Paul Moayyedi in an interview with Dr. Roman Jaeschke: part 2.}, journal = {Polish archives of internal medicine}, volume = {127}, number = {2}, pages = {137-138}, doi = {10.20452/pamw.3963}, pmid = {28267142}, issn = {1897-9483}, mesh = {Clostridium Infections/*therapy ; Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Microbiota ; }, }
@article {pmid28267044, year = {2017}, author = {Huang, Z and Peng, K and Li, X and Zhao, R and You, J and Cheng, X and Wang, Z and Wang, Y and Wu, B and Wang, H and Zeng, H and Yu, Z and Zheng, C and Wang, Y and Huang, Y}, title = {Mutations in Interleukin-10 Receptor and Clinical Phenotypes in Patients with Very Early Onset Inflammatory Bowel Disease: A Chinese VEO-IBD Collaboration Group Survey.}, journal = {Inflammatory bowel diseases}, volume = {23}, number = {4}, pages = {578-590}, doi = {10.1097/MIB.0000000000001058}, pmid = {28267044}, issn = {1536-4844}, mesh = {Age of Onset ; Asian People/genetics ; Case-Control Studies ; China ; Female ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Infant, Newborn ; Inflammatory Bowel Diseases/*genetics ; Interleukin-10 Receptor alpha Subunit/*genetics ; Interleukin-10 Receptor beta Subunit/*genetics ; Male ; *Mutation ; *Phenotype ; }, abstract = {BACKGROUND: Interleukin-10 (IL10) signaling plays an important role in the pathogenesis of very early onset inflammatory bowel disease (VEO-IBD) in children. However, little is known about the role of the IL10 axis in children with VEO-IBD in China.<br><br>METHODS: The Chinese VEO-IBD Collaboration Group was created to collect clinical and genetic data from patients deficient in IL10 and the IL10 receptor. High-throughput sequencing was performed to identify mutations in these genes.<br><br>RESULTS: We identified 32 compound heterozygous mutations and 9 homozygous mutations in IL10 receptor subunit alpha and 1 homozygous mutation in IL10 receptor subunit beta. Among these mutations, 10 novel mutations were identified, and 6 pathogenic mutations had been previously described. In patients with IL10 receptor subunit alpha mutations, c.301C>T (p.R101RW) and c.537 G>A (p.T179T) were the most common mutations. For 88.1% of the patients, the initial symptom was diarrhea, with a time of onset of 10.4 &#xb1; 8.0 days. Oral ulcers were the first symptom in 23.8% of the patients, with a time of onset of 9.7 &#xb1; 2.8 days. Extraintestinal manifestations included perianal abscesses (22/42), perianal fistulas (23/42), oral ulcers (20/42), and recurrent eczema (15/42). Twelve patients underwent enterostomy. These patients also had lower average Z scores in height-for-age and weight-for-age. Various treatment strategies were used, including fecal microbiota transplantation; however, only hematopoietic stem cell transplantation was efficacious.<br><br>CONCLUSIONS: This study identified genotypes and phenotypes of Chinese VEO-IBD infants with IL10 receptor mutations. Our study expands the current knowledge on the involvement of the IL10 axis in patients with VEO-IBD.}, }
@article {pmid28267006, year = {2017}, author = {Muñoz-Duyos, A and Navarro-Luna, A and Pardo-Aranda, F and Caballero, JM and Borrat, P and Maristany, C and Pando, JA and Veloso, E}, title = {Gracilis Muscle Interposition for Rectourethral Fistula After Laparoscopic Prostatectomy: A Prospective Evaluation and Long-term Follow-up.}, journal = {Diseases of the colon and rectum}, volume = {60}, number = {4}, pages = {393-398}, doi = {10.1097/DCR.0000000000000763}, pmid = {28267006}, issn = {1530-0358}, mesh = {Aged ; Cohort Studies ; Follow-Up Studies ; Gracilis Muscle/*transplantation ; Humans ; Laparoscopy ; Male ; Middle Aged ; Postoperative Complications/*surgery ; Prospective Studies ; *Prostatectomy ; Prostatic Neoplasms/*surgery ; Rectal Fistula/*surgery ; Retrospective Studies ; *Surgical Flaps ; Treatment Outcome ; Urethral Diseases/*surgery ; Urinary Fistula/*surgery ; }, abstract = {BACKGROUND: Postoperative rectourethral fistula after radical prostatectomy is an infrequent but very serious problem.<br><br>OBJECTIVE: We aimed to describe our experience with transperineal repair and unilateral gracilis muscle interposition in patients with rectourethral fistula after radical prostatectomy in nonradiated prostate cancer.<br><br>DESIGN: This was a cohort study.<br><br>SETTINGS: All of the procedures were performed at the same hospital by the same multidisciplinary team made up of a senior colorectal surgeon and a senior urologist.<br><br>PATIENTS: Patients with postoperative rectourethral fistula after laparoscopic prostatectomy were included.<br><br>INTERVENTION: Transperineal fistula repair and gracilis muscle interposition were included.<br><br>MAIN OUTCOME MEASURES: Fistula healing rate was measured.<br><br>RESULTS: Nine patients with postoperative rectourethral fistula were treated between November 2009 and February 2016. Four of them had received other previous treatments without success, and 5 had previously been treated with this technique. Seven patients had a fecal diverting stoma. After a median follow-up of 54 months (range, 2-72), all of the fistulas had successfully healed, and, to date, the patients remain asymptomatic without urinary diversion. Fecal diversion was closed in all but 1 patient. No intraoperative or infectious complications were detected. With the results of our series, we present specific technical details of our technique and hope to provide additional evidence of the low morbidity profile and excellent healing rate of this treatment. Moreover, we note that, although small, this series corresponds with a homogeneous group of patients with rectourethral fistula after radical prostatectomy in nonradiated prostate cancer.<br><br>LIMITATIONS: This is a small but very homogeneous group of patients.<br><br>CONCLUSIONS: Simple repair with perineal gracilis muscle interposition is a safe and effective technique for the treatment of postoperative rectourethral fistulas after nonradiated prostate cancer surgery.}, }
@article {pmid28261667, year = {2017}, author = {Vlasova, AN and Paim, FC and Kandasamy, S and Alhamo, MA and Fischer, DD and Langel, SN and Deblais, L and Kumar, A and Chepngeno, J and Shao, L and Huang, HC and Candelero-Rueda, RA and Rajashekara, G and Saif, LJ}, title = {Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs.}, journal = {mSphere}, volume = {2}, number = {2}, pages = {}, pmid = {28261667}, issn = {2379-5042}, support = {R01 AI099451/AI/NIAID NIH HHS/United States ; }, abstract = {Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases. Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. In this study, we used neonatal gnotobiotic (Gn) pigs transplanted with the fecal microbiota of a healthy 2-month-old infant (HIFM) and fed protein-deficient or -sufficient bovine milk diets. Protein deficiency induced hypoproteinemia, hypoalbuminemia, hypoglycemia, stunting, and generalized edema in Gn pigs, as observed in protein-malnourished children. Irrespective of the diet, human rotavirus (HRV) infection early, at HIFM posttransplantation day 3 (PTD3), resulted in adverse health effects and higher mortality rates (45 to 75%) than later HRV infection (PTD10). Protein malnutrition exacerbated HRV infection and affected the morphology and function of the small intestinal epithelial barrier. In pigs infected with HRV at PTD10, there was a uniform decrease in the function and/or frequencies of natural killer cells, plasmacytoid dendritic cells, and CD103[+] and apoptotic mononuclear cells and altered gene expression profiles of intestinal epithelial cells (chromogranin A, mucin 2, proliferating cell nuclear antigen, SRY-Box 9, and villin). Thus, we have established the first HIFM-transplanted neonatal pig model that recapitulates major aspects of protein malnutrition in children and can be used to evaluate physiologically relevant interventions. Our findings provide an explanation of why nutrient-rich diets alone may lack efficacy in malnourished children. IMPORTANCE Malnutrition and rotavirus infection, prevalent in developing countries, individually and in combination, affect the health of millions of children, compromising their immunity and increasing the rates of death from infectious diseases. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. We have established the first human infant microbiota-transplanted neonatal pig model of childhood malnutrition that reproduced the impaired immune, intestinal, and other physiological functions seen in malnourished children. This model can be used to evaluate relevant dietary and other health-promoting interventions. Our findings provide an explanation of why adequate nutrition alone may lack efficacy in malnourished children.}, }
@article {pmid28257308, year = {2017}, author = {Cheung, AC and Lazaridis, KN and LaRusso, NF and Gores, GJ}, title = {Emerging pharmacologic therapies for primary sclerosing cholangitis.}, journal = {Current opinion in gastroenterology}, volume = {33}, number = {3}, pages = {149-157}, pmid = {28257308}, issn = {1531-7056}, support = {P30 DK084567/DK/NIDDK NIH HHS/United States ; R01 DK057993/DK/NIDDK NIH HHS/United States ; R01 DK063947/DK/NIDDK NIH HHS/United States ; R01 DK084960/DK/NIDDK NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Chenodeoxycholic Acid/analogs &amp; derivatives/therapeutic use ; Cholangitis, Sclerosing/*drug therapy/microbiology ; Clinical Trials as Topic/methods ; Fecal Microbiota Transplantation ; Fibric Acids/therapeutic use ; Gastrointestinal Microbiome/drug effects ; Humans ; Immunologic Factors/therapeutic use ; Molecular Targeted Therapy/*methods/trends ; Organic Anion Transporters, Sodium-Dependent/antagonists &amp; inhibitors ; Probiotics/therapeutic use ; Symporters/antagonists &amp; inhibitors ; Ursodeoxycholic Acid/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: The only currently approved treatment for primary sclerosing cholangitis (PSC) is liver transplantation, with a median time to transplant of 12-18 years after diagnosis. There are a number of emerging drugs that have the potential to meet this critically unmet need that will be summarized and discussed herein.<br><br>RECENT FINDINGS: Although the cause of PSC is unknown, there are a number of novel therapeutics under development. These drugs target presumed pathogenic mechanisms largely extrapolated from ex-vivo and in-vivo preclinical models, as well as translational observations.<br><br>SUMMARY: Future therapeutic strategies for PSC may include a multitude of complex pathogenic mechanisms encompassing pathways of immunomodulation, the microbiome and inflammation-related fibrosis.}, }
@article {pmid28251905, year = {2017}, author = {De Palma, G and Lynch, MD and Lu, J and Dang, VT and Deng, Y and Jury, J and Umeh, G and Miranda, PM and Pigrau Pastor, M and Sidani, S and Pinto-Sanchez, MI and Philip, V and McLean, PG and Hagelsieb, MG and Surette, MG and Bergonzelli, GE and Verdu, EF and Britz-McKibbin, P and Neufeld, JD and Collins, SM and Bercik, P}, title = {Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice.}, journal = {Science translational medicine}, volume = {9}, number = {379}, pages = {}, doi = {10.1126/scitranslmed.aaf6397}, pmid = {28251905}, issn = {1946-6242}, support = {//CIHR/Canada ; }, mesh = {Adult ; Animals ; Anxiety/blood/metabolism/physiopathology ; *Behavior, Animal ; Case-Control Studies ; Colon/immunology/microbiology ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*physiopathology ; Gastrointestinal Transit ; Germ-Free Life ; Humans ; Irritable Bowel Syndrome/*microbiology ; Male ; Metabolomics ; Mice ; Tissue Donors ; }, abstract = {Irritable bowel syndrome (IBS) is a common disorder characterized by altered gut function and often is accompanied by comorbid anxiety. Although changes in the gut microbiota have been documented, their relevance to the clinical expression of IBS is unknown. To evaluate a functional role for commensal gut bacteria in IBS, we colonized germ-free mice with the fecal microbiota from healthy control individuals or IBS patients with diarrhea (IBS-D), with or without anxiety, and monitored gut function and behavior in the transplanted mice. Microbiota profiles in recipient mice clustered according to the microbiota profiles of the human donors. Mice receiving the IBS-D fecal microbiota showed a taxonomically similar microbial composition to that of mice receiving the healthy control fecal microbiota. However, IBS-D mice showed different serum metabolomic profiles. Mice receiving the IBS-D fecal microbiota, but not the healthy control fecal microbiota, exhibited faster gastrointestinal transit, intestinal barrier dysfunction, innate immune activation, and anxiety-like behavior. These results indicate the potential of the gut microbiota to contribute to both intestinal and behavioral manifestations of IBS-D and suggest the potential value of microbiota-directed therapies in IBS patients.}, }
@article {pmid28250470, year = {2017}, author = {Thomas, H}, title = {IBD: FMT induces clinical remission in ulcerative colitis.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {14}, number = {4}, pages = {196}, pmid = {28250470}, issn = {1759-5053}, mesh = {*Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Remission Induction ; }, }
@article {pmid28250469, year = {2017}, author = {Dickson, I}, title = {Gut microbiota: Diagnosing IBD with the gut microbiome.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {14}, number = {4}, pages = {195}, pmid = {28250469}, issn = {1759-5053}, mesh = {Dysbiosis ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases ; }, }
@article {pmid28249379, year = {2017}, author = {Park, JH}, title = {Clinical Usefulness of Fecal Microbiota Transplantation.}, journal = {Journal of neurogastroenterology and motility}, volume = {23}, number = {2}, pages = {149-150}, pmid = {28249379}, issn = {2093-0879}, }
@article {pmid28247264, year = {2017}, author = {Sidhu, SS and Goyal, O and Kishore, H and Sidhu, S}, title = {New paradigms in management of alcoholic hepatitis: a review.}, journal = {Hepatology international}, volume = {11}, number = {3}, pages = {255-267}, pmid = {28247264}, issn = {1936-0541}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Animals ; Anti-Inflammatory Agents/therapeutic use ; Fecal Microbiota Transplantation/methods ; Female ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Hepatic Encephalopathy/complications/epidemiology/etiology ; Hepatitis, Alcoholic/*epidemiology/mortality/physiopathology/*therapy ; Hepatocytes/*drug effects/pathology ; Humans ; Inflammation/pathology ; Liver/drug effects/*pathology/physiopathology ; Liver Diseases/drug therapy ; Liver Regeneration/*drug effects ; Liver Transplantation/methods ; Male ; Mice ; Models, Animal ; Molecular Targeted Therapy/methods ; Necrosis/pathology ; Pentoxifylline/therapeutic use ; Phosphodiesterase Inhibitors/therapeutic use ; Prednisolone/therapeutic use ; Severity of Illness Index ; }, abstract = {Severe alcoholic hepatitis (SAH) is defined by modified Maddrey discriminant function ≥32 or Model for End-Stage Liver Disease (MELD) >21 and/or hepatic encephalopathy. It has a 3-month mortality rate ≥30-70 %. Patients with severe alcoholic hepatitis need combined, i.e., static (MELD score) and dynamic (Lille's score), prognostication. Systemic inflammation and poor regeneration are hallmarks of SAH, rather than intrahepatic inflammation. SAH is characterized by dysregulated and uncontrolled systemic inflammatory response followed by weak compensatory antiinflammatory response that leads to increased susceptibility to infection and multiple organ failure. Massive necrosis of hepatocytes exceeds the proliferative capacity of hepatocytes. Liver progenitor cells proliferate to form narrow ductules which radiate out into the damaged liver parenchyma. Corticosteroids have been the standard-of-care therapy, albeit controversial. However, the recent Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial revealed that prednisolone was not associated with a significant reduction in 28-day mortality, with no improvement in outcomes at 90 days or 1 year. A paradigm shift from antiinflammatory therapy such as corticosteroids to liver regeneration treatment, e.g., granulocyte-colony stimulating factor, molecular targeted treatments, and fecal microbiota transplantation, for severe alcoholic hepatitis is taking place. Liver transplantation should be offered to select patients with severe alcoholic hepatitis who are nonresponsive to medical treatment.}, }
@article {pmid28246016, year = {2017}, author = {Hong, CP and Park, A and Yang, BG and Yun, CH and Kwak, MJ and Lee, GW and Kim, JH and Jang, MS and Lee, EJ and Jeun, EJ and You, G and Kim, KS and Choi, Y and Park, JH and Hwang, D and Im, SH and Kim, JF and Kim, YK and Seoh, JY and Surh, CD and Kim, YM and Jang, MH}, title = {Gut-Specific Delivery of T-Helper 17 Cells Reduces Obesity and Insulin Resistance in Mice.}, journal = {Gastroenterology}, volume = {152}, number = {8}, pages = {1998-2010}, doi = {10.1053/j.gastro.2017.02.016}, pmid = {28246016}, issn = {1528-0012}, mesh = {*Adoptive Transfer ; Animals ; Cells, Cultured ; Diet, High-Fat ; Disease Models, Animal ; Feces/microbiology ; Gastrointestinal Microbiome/immunology ; Genotype ; Homeodomain Proteins/genetics/metabolism ; Host-Pathogen Interactions ; *Immunity, Mucosal ; *Insulin Resistance ; Integrin beta Chains/genetics/metabolism ; Interleukin-17/deficiency/genetics ; Intestine, Small/*immunology/metabolism/microbiology ; Male ; Metabolic Syndrome/genetics/immunology/microbiology/*prevention &amp; control ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/genetics/immunology/microbiology/*prevention &amp; control ; Phenotype ; Th17 Cells/immunology/microbiology/*transplantation ; Time Factors ; Vitamin A Deficiency/complications ; }, abstract = {BACKGROUND &amp; AIMS: Obesity and metabolic syndrome have been associated with alterations to the intestinal microbiota. However, few studies examined the effects of obesity on the intestinal immune system. We investigated changes in subsets of intestinal CD4[+] T-helper (TH) cells with obesity and the effects of gut-tropic TH17 cells in mice on a high-fat diet (HFD).<br><br>METHODS: We isolated immune cells from small intestine and adipose tissue of C57BL/6 mice fed a normal chow diet or a HFD for 10 weeks and analyzed the cells by flow cytometry. Mice fed a vitamin A-deficient HFD were compared with mice fed a vitamin A-sufficient HFD. Obese RAG1-deficient mice were given injections of only regulatory T cells or a combination of regulatory T cells and TH17 cells (wild type or deficient in integrin &#x3b2;7 subunit or interleukin 17 [IL17]). Mice were examined for weight gain, fat mass, fatty liver, glucose tolerance, and insulin resistance. Fecal samples were collected before and after T cell transfer and analyzed for microbiota composition by metagenomic DNA sequencing and quantitative polymerase chain reaction.<br><br>RESULTS: Mice placed on a HFD became obese, which affected the distribution of small intestinal CD4[+] TH cells. Intestinal tissues from obese mice had significant reductions in the proportion of TH17 cells but increased proportion of TH1 cells, compared with intestinal tissues from nonobese mice. Depletion of vitamin A in obese mice further reduced the proportion of TH17 cells in small intestine; this reduction correlated with more weight gain and worsening of glucose intolerance and insulin resistance. Adoptive transfer of in&#xa0;vitro-differentiated gut-tropic TH17 cells to obese mice reduced these metabolic defects, which required the integrin &#x3b2;7 subunit and IL17. Delivery of TH17 cells to intestines of mice led to expansion of commensal microbes associated with leanness.<br><br>CONCLUSIONS: In mice, intestinal TH17 cells contribute to development of a microbiota that&#xa0;maintains metabolic homeostasis, via IL17. Gut-homing TH17 cells might be used to reduce metabolic disorders in obese individuals.}, }
@article {pmid28245856, year = {2017}, author = {Galloway-Peña, JR and Smith, DP and Sahasrabhojane, P and Wadsworth, WD and Fellman, BM and Ajami, NJ and Shpall, EJ and Daver, N and Guindani, M and Petrosino, JF and Kontoyiannis, DP and Shelburne, SA}, title = {Characterization of oral and gut microbiome temporal variability in hospitalized cancer patients.}, journal = {Genome medicine}, volume = {9}, number = {1}, pages = {21}, pmid = {28245856}, issn = {1756-994X}, support = {L30 CA209245/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; T32 CA096520/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Anti-Bacterial Agents/*pharmacology ; Antineoplastic Agents/*pharmacology/therapeutic use ; Bacteria/genetics/isolation &amp; purification/metabolism ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Leukemia, Myeloid, Acute/drug therapy/*microbiology ; Male ; Middle Aged ; RNA, Ribosomal, 16S ; Saliva/microbiology ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Understanding longitudinal variability of the microbiome in ill patients is critical to moving microbiome-based measurements and therapeutics into clinical practice. However, the vast majority of data regarding microbiome stability are derived from healthy subjects. Herein, we sought to determine intra-patient temporal microbiota variability, the factors driving such variability, and its clinical impact in an extensive longitudinal cohort of hospitalized cancer patients during chemotherapy.<br><br>METHODS: The stool (n&#x2009;=&#x2009;365) and oral (n&#x2009;=&#x2009;483) samples of 59 patients with acute myeloid leukemia (AML) undergoing induction chemotherapy (IC) were sampled from initiation of chemotherapy until neutrophil recovery. Microbiome characterization was performed via analysis of 16S rRNA gene sequencing. Temporal variability was determined using coefficients of variation (CV) of the Shannon diversity index (SDI) and unweighted and weighted UniFrac distances per patient, per site. Measurements of intra-patient temporal variability and patient stability categories were analyzed for their correlations with genera abundances. Groups of patients were analyzed to determine if patients with adverse outcomes had significantly different levels of microbiome temporal variability. Potential clinical drivers of microbiome temporal instability were determined using multivariable regression analyses.<br><br>RESULTS: Our cohort evidenced a high degree of intra-patient temporal instability of stool and oral microbial diversity based on SDI CV. We identified statistically significant differences in the relative abundance of multiple taxa amongst individuals with different levels of microbiota temporal stability. Increased intra-patient temporal variability of the oral SDI was correlated with increased risk of infection during IC (P&#x2009;=&#x2009;0.02), and higher stool SDI CVs were correlated with increased risk of infection 90&#xa0;days post-IC (P&#x2009;=&#x2009;0.04). Total days on antibiotics was significantly associated with increased temporal variability of both oral microbial diversity (P&#x2009;=&#x2009;0.03) and community structure (P&#x2009;=&#x2009;0.002).<br><br>CONCLUSIONS: These data quantify the longitudinal variability of the oral and gut microbiota in AML patients, show that increased variability was correlated with adverse clinical outcomes, and offer the possibility of using stabilizing taxa as a method of focused microbiome repletion. Furthermore, these results support the importance of longitudinal microbiome sampling and analyses, rather than one time measurements, in research and future clinical practice.}, }
@article {pmid28242755, year = {2017}, author = {Cui, M and Xiao, H and Li, Y and Zhou, L and Zhao, S and Luo, D and Zheng, Q and Dong, J and Zhao, Y and Zhang, X and Zhang, J and Lu, L and Wang, H and Fan, S}, title = {Faecal microbiota transplantation protects against radiation-induced toxicity.}, journal = {EMBO molecular medicine}, volume = {9}, number = {4}, pages = {448-461}, pmid = {28242755}, issn = {1757-4684}, support = {R01 AT005076/AT/NCCIH NIH HHS/United States ; R01 GM063075/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; Female ; Intestinal Mucosa/pathology ; Intestine, Small/pathology ; Male ; Mice ; Radiation Injuries, Experimental/pathology/*prevention &amp; control ; Radiation Protection/*methods ; Survival Analysis ; }, abstract = {Severe radiation exposure may cause acute radiation syndrome, a possibly fatal condition requiring effective therapy. Gut microbiota can be manipulated to fight against many diseases. We explored whether intestinal microbe transplantation could alleviate radiation-induced toxicity. High-throughput sequencing showed that gastrointestinal bacterial community composition differed between male and female mice and was associated with susceptibility to radiation toxicity. Faecal microbiota transplantation (FMT) increased the survival rate of irradiated animals, elevated peripheral white blood cell counts and improved gastrointestinal tract function and intestinal epithelial integrity in irradiated male and female mice. FMT preserved the intestinal bacterial composition and retained mRNA and long non-coding RNA expression profiles of host small intestines in a sex-specific fashion. Despite promoting angiogenesis, sex-matched FMT did not accelerate the proliferation of cancer cells in vivo FMT might serve as a therapeutic to mitigate radiation-induced toxicity and improve the prognosis of tumour patients after radiotherapy.}, }
@article {pmid28239315, year = {2017}, author = {Mizuno, S and Nanki, K and Matsuoka, K and Saigusa, K and Ono, K and Arai, M and Sugimoto, S and Kiyohara, H and Nakashima, M and Takeshita, K and Naganuma, M and Suda, W and Hattori, M and Kanai, T}, title = {Single fecal microbiota transplantation failed to change intestinal microbiota and had limited effectiveness against ulcerative colitis in Japanese patients.}, journal = {Intestinal research}, volume = {15}, number = {1}, pages = {68-74}, pmid = {28239315}, issn = {1598-9100}, abstract = {BACKGROUND/AIMS: Recent developments in analytical techniques including next-generation sequencing have clarified the correlation between intestinal microbiota and inflammatory bowel disease. Fecal microbiota transplantation (FMT) for patients with ulcerative colitis (UC) is proposed as a potential approach to resolving their dysbiosis; however, its safety and efficacy have not been confirmed. This single-arm, open-label, non-randomized study aimed to evaluate the safety and efficacy of FMT for Japanese patients with UC as the first registered clinical trial in Japan.<br><br>METHODS: We enrolled 10 patients with active UC despite medical therapy. The donors were the patients' relatives and were carefully screened for infectious diseases. Fecal material was administered via colonoscopy, and the primary endpoint was the presence or absence of serious adverse events related to FMT. The secondary endpoint was a change in partial Mayo score at 12 weeks post-FMT. Scores &#x2264;2 were considered a clinical response. Fecal samples were collected to follow changes in gut microbiota, while extracted complementary DNA were analyzed by a next-generation sequencer. We obtained written informed consent from all patients and donors. This study was approved by our Institutional Review Board and is registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN 000012814).<br><br>RESULTS: Five patients with moderate disease and five with severe disease were enrolled. No severe adverse effects were observed. One patient achieved clinical response; however, none of the patients' microbiota diversity recovered to the donor levels.<br><br>CONCLUSIONS: The use of single FMT for UC was safe; however, we failed to show its clinical efficacy and potential to change the intestinal microbiota.}, }
@article {pmid28237504, year = {2017}, author = {Davido, B and Batista, R and Michelon, H and Lepainteur, M and Bouchand, F and Lepeule, R and Salomon, J and Vittecoq, D and Duran, C and Escaut, L and Sobhani, I and Paul, M and Lawrence, C and Perronne, C and Chast, F and Dinh, A}, title = {Is faecal microbiota transplantation an option to eradicate highly drug-resistant enteric bacteria carriage?.}, journal = {The Journal of hospital infection}, volume = {95}, number = {4}, pages = {433-437}, doi = {10.1016/j.jhin.2017.02.001}, pmid = {28237504}, issn = {1532-2939}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carrier State/*microbiology/*therapy ; *Drug Resistance, Bacterial ; Enterobacteriaceae/*isolation &amp; purification ; Enterobacteriaceae Infections/microbiology/therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Gram-Positive Bacterial Infections/microbiology/therapy ; Humans ; Male ; Middle Aged ; Pilot Projects ; Prospective Studies ; Treatment Outcome ; Vancomycin-Resistant Enterococci/*isolation &amp; purification ; }, abstract = {Carbapenem-resistant Enterobacteriaceae (CRE) or vancomycin-resistant enterococci (VRE) carriage present a major public health challenge. Decolonization strategies are lacking. We aimed to evaluate the impact of faecal microbiota transplantation (FMT) on a cohort of patients with digestive tract colonization by CRE or VRE. Eight patients were included: six carrying CRE and two colonized by VRE. One month after FMT, two patients were free from CRE carriage, and another patient was free from VRE after three months. In our experience, this strategy is safe.}, }
@article {pmid28235986, year = {2017}, author = {Lübbert, C and Salzberger, B and Mössner, J}, title = {[Fecal microbiota transplantation].}, journal = {Der Internist}, volume = {58}, number = {5}, pages = {456-468}, pmid = {28235986}, issn = {1432-1289}, mesh = {Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Germany ; Humans ; }, abstract = {The human intestinal microbiome has important metabolic and immunological functions for the host and is part of the defense against pathogens in the gastrointestinal tract. Antibiotics, probiotics, dietary measures, such as prebiotics, and the relatively newly established method of fecal microbiota transplantation (FMT, also known as fecal microbiome transfer) all influence the intestinal microbiome. The FMT procedure comprises the transmission of fecal microorganisms from a healthy donor into the gastrointestinal tract of a patient. The aim of this intervention is to restore a normal microbiome in patients with diseases associated with dysbiosis. The only indication for FMT is currently multiple recurrence of Clostridium difficile infections. Approximately 85% of affected patients can be successfully treated by FMT compared to only about 30% treated conventionally with vancomycin. Other possible therapeutic applications are chronic inflammatory and functional bowel diseases, insulin resistance and morbid obesity but these have to be evaluated further in clinical trials. Knowledge on the optimal donor, the best dosage and the most appropriate route of administration is still limited. A careful donor selection is necessary. The implementation of FMT in Germany is subject to the Medicines Act (Arzneimittelgesetz, AMG) with a duty of disclosure and personal implementation by the attending physician. By documentation in a central register long-term effects and side effects of FMT have to be evaluated.}, }
@article {pmid28232086, year = {2017}, author = {Weber, D and Jenq, RR and Peled, JU and Taur, Y and Hiergeist, A and Koestler, J and Dettmer, K and Weber, M and Wolff, D and Hahn, J and Pamer, EG and Herr, W and Gessner, A and Oefner, PJ and van den Brink, MRM and Holler, E}, title = {Microbiota Disruption Induced by Early Use of Broad-Spectrum Antibiotics Is an Independent Risk Factor of Outcome after Allogeneic Stem Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {23}, number = {5}, pages = {845-852}, pmid = {28232086}, issn = {1523-6536}, support = {R01 AI101406/AI/NIAID NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; R01 AI100288/AI/NIAID NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; HHSN272200900059C/AI/NIAID NIH HHS/United States ; R01 HL069929/HL/NHLBI NIH HHS/United States ; K23 AI095398/AI/NIAID NIH HHS/United States ; R01 AI080455/AI/NIAID NIH HHS/United States ; P01 CA033049/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/adverse effects/*pharmacology ; Clostridium/drug effects ; Female ; Gastrointestinal Microbiome/*drug effects ; Graft vs Host Disease/etiology/mortality ; Humans ; Infections/etiology/mortality ; Male ; Retrospective Studies ; Risk Factors ; Stem Cell Transplantation/adverse effects/*methods/mortality ; Survival Analysis ; Time-to-Treatment ; Transplantation, Homologous ; Treatment Outcome ; Young Adult ; }, abstract = {In allogeneic stem cell transplantation (ASCT), systemic broad-spectrum antibiotics are frequently used for treatment of infectious complications, but their effect on microbiota composition is still poorly understood. This retrospective analysis of 621 patients who underwent ASCT at the University Medical Center of Regensburg and Memorial Sloan Kettering Cancer Center in New York assessed the impact of timing of peritransplant antibiotic treatment on intestinal microbiota composition as well as transplant-related mortality (TRM) and overall survival. Early exposure to antibiotics was associated with lower urinary 3-indoxyl sulfate levels (P < .001) and a decrease in fecal abundance of commensal Clostridiales (P = .03) compared with late antibiotic treatment, which was particularly significant (P = .005) for Clostridium cluster XIVa in the Regensburg group. Earlier antibiotic treatment before ASCT was further associated with a higher TRM (34%, 79/236) compared with post-ASCT (21%, 62/297, P = .001) or no antibiotics (7%, 6/88, P < .001). Timing of antibiotic treatment was the dominant independent risk factor for TRM (HR, 2.0; P ≤ .001) in multivariate analysis besides increase age (HR, 2.15; P = .004), reduced Karnofsky performance status (HR, 1.47; P = .03), and female donor-male recipient sex combination (HR, 1.56; P = .02) A competing risk analysis revealed the independent effect of early initiation of antibiotics on graft-versus-host disease-related TRM (P = .004) in contrast to infection-related TRM and relapse (not significant). The poor outcome associated with early administration of antibiotic therapy that is active against commensal organisms, and specifically the possibly protective Clostridiales, calls for the use of Clostridiales-sparing antibiotics and rapid restoration of microbiota diversity after cessation of antibiotic treatment.}, }
@article {pmid28231890, year = {2016}, author = {Kessler, L and Abély, M}, title = {[Pancreatic infringement exocrine and endocrine in cystic fibrosis].}, journal = {Archives de pediatrie : organe officiel de la Societe francaise de pediatrie}, volume = {23}, number = {12S}, pages = {12S21-12S32}, doi = {10.1016/S0929-693X(17)30059-3}, pmid = {28231890}, issn = {1769-664X}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; Cystic Fibrosis/*diagnosis/*physiopathology/therapy ; Diabetes Mellitus/*diagnosis/*physiopathology/therapy ; Energy Intake/physiology ; Exocrine Pancreatic Insufficiency/*diagnosis/*physiopathology/therapy ; Glucose Tolerance Test ; Humans ; Infant ; Islets of Langerhans/*physiopathology ; Life Expectancy ; Pancreas, Exocrine/*physiopathology ; Pancreatic Extracts/therapeutic use ; Proton Pump Inhibitors/therapeutic use ; Young Adult ; }, abstract = {The exocrine pancreatic insufficiency affects more than 80% of cystic fibrosis (CF) infants. Pancreatic insufficiency is diagnosed by low levels of fecal elastase. An optimal caloric intake, a pancreatic enzyme treatment are the keys to maintain a good nutritional status. The fat soluble vitamins supplementation will be associated with pancreatic enzymes treatment and will be adapted to plasma levels. Iron and oligo-element deficiency such as zinc is common. The pancreatic enzymes function is not optimal in the proximal bowel: the intraluminal intestinal pH is low because of the absence of bicarbonate release by the pancreas. The use of proton pump inhibitors may improve the functionality of pancreatic enzymes treatment. New therapies such as ivacaftor in patients with a G551D mutation allows a weight gain in particular by restoring intestinal pH similar to controls. Lengthening of the life expectancy of patients with CF is accompanied by the emergence new aspects of the disease, especially diabetes, favored by pancreatic cystic fibrosis resulting in an anatomical destruction of pancreatic islets. Currently, diabetes affects a third of the patients after 20 years, and half after 30 years. Cystic fibrosis-related diabetes is a major factor of morbidity-mortality in all stages of the disease and is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years. Its pathophysiology combines a lack of insulin secretion, an insulin resistance secondary to chronic infection, and a decrease in the production of the GIP and GLP-1. The insulin secretion depending on the channel chlorine (Cystic Fibrosis Transmembrane conductance Regulator [CFTR]) activity at the membrane surface of insulin cell is reduced prior to the occurrence of pancreatic histological lesions. At the stage of diabetes, obtaining a normoglycemia by insulin treatment began very early allows to slow the decline of lung function and nutritional status. Given the silent phase of diabetes, screening it is recommended by the realization of an annual OGTT from 10 years of age, or before in severe forms of CF. New treatments of CF able to target CFTR showed their efficacy in slowing the decline of lung function, and could also contribute to slow or prevent the onset of diabetes.}, }
@article {pmid28231570, year = {2017}, author = {Sakai, Y and Komai, Y and Saito, N and Ito, M and Sakuraba, M}, title = {Analysis of a Surgical Treatment for Persistent Urorectal Fistulas after Radical Cancer Surgery: A Comparison of Prostate Cancer and Rectal Cancer.}, journal = {Urologia internationalis}, volume = {99}, number = {1}, pages = {56-62}, doi = {10.1159/000457835}, pmid = {28231570}, issn = {1423-0399}, mesh = {Aged ; Gracilis Muscle/*transplantation ; Humans ; Male ; Middle Aged ; Prostatectomy/*adverse effects ; Prostatic Neoplasms/pathology/*surgery ; Rectal Fistula/diagnosis/etiology/*surgery ; Rectal Neoplasms/pathology/*surgery ; Rectus Abdominis/*surgery ; Retrospective Studies ; *Surgical Flaps/adverse effects ; Treatment Outcome ; Urinary Fistula/diagnosis/etiology/*surgery ; }, abstract = {INTRODUCTION: The study aimed to present our experience of surgical treatment for urorectal fistulas (URF) that develop after cancer surgery.<br><br>MATERIALS AND METHODS: Fourteen patients with URF who were treated at our institution from 2005 through 2015 were retrospectively analyzed. Among these, 7 patients had previous surgical treatment of prostate cancer (PC) and the other 7 had been treated for rectal cancer (RC). The fistula was resected through a perineal incision, and the urinary and fecal defects were separately closed with the hinge flap method followed by interposition of a muscle flap transfer.<br><br>RESULTS: The overall fistula closure rate was 79%. Although the closure rate of the URF was lower in patients with previous RC surgery compared to the PC patients (57 vs. 100%), it did not reach statistical significance.<br><br>CONCLUSIONS: URF treatment using an interposition muscle flap offers a high success rate of fistula closure. However, complicated fistulas occurring after RC surgery involving the prostate or the seminal vesicle might be difficult to repair by this surgery alone.}, }
@article {pmid28230610, year = {2017}, author = {Wang, J and Gu, J and Wang, Y and Lin, K and Liu, S and Lu, H and Zhang, T and Yu, G}, title = {16S rDNA Gene Sequencing Analysis in Functional Dyspepsia Treated With Fecal Microbiota Transplantation.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {64}, number = {3}, pages = {e80-e82}, doi = {10.1097/MPG.0000000000001476}, pmid = {28230610}, issn = {1536-4801}, mesh = {Child, Preschool ; Dyspepsia/genetics/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces ; Humans ; Male ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, RNA/methods ; }, }
@article {pmid28222801, year = {2017}, author = {Sarveazad, A and Newstead, GL and Mirzaei, R and Joghataei, MT and Bakhtiari, M and Babahajian, A and Mahjoubi, B}, title = {A new method for treating fecal incontinence by implanting stem cells derived from human adipose tissue: preliminary findings of a randomized double-blind clinical trial.}, journal = {Stem cell research &amp; therapy}, volume = {8}, number = {1}, pages = {40}, pmid = {28222801}, issn = {1757-6512}, mesh = {Adipocytes/*cytology/physiology ; Adipose Tissue/cytology/physiology ; Adult ; Aged ; Anal Canal/diagnostic imaging/physiopathology/surgery ; Cell Differentiation ; Double-Blind Method ; Electromyography ; Fecal Incontinence/diagnostic imaging/physiopathology/surgery/*therapy ; Female ; Humans ; Male ; Middle Aged ; Muscle Cells/*cytology/physiology ; Sphincterotomy, Transduodenal/methods ; *Stem Cell Transplantation ; Stem Cells/*cytology/physiology ; Transplantation, Homologous ; Ultrasonography ; }, abstract = {BACKGROUND: Anal sphincter defects are a major cause of fecal incontinence causing negative effects on daily life, social interactions, and mental health. Because human adipose-derived stromal/stem cells (hADSCs) are easier and safer to access, secrete high levels of growth factor, and have the potential to differentiate into muscle cells, we investigated the ability of hADSCs to improve anal sphincter incontinence.<br><br>METHODS: The present randomized double-blind clinical trial was performed on patients with sphincter defects. They were categorized into a cell group (n&#x2009;=&#x2009;9) and a control group (n&#x2009;=&#x2009;9). Either 6&#x2009;&#xd7;&#x2009;10[6] hADSCs per 3 ml suspended in phosphate buffer saline (treatment) or 3 ml phosphate buffer saline (placebo) was injected. Two months after surgery, the Wexner score, endorectal sonography, and electromyography (EMG) results were recorded.<br><br>RESULTS: Comparing Wexner scores in the cell group and the control group showed no significant difference. In our EMG and endorectal sonography analysis using ImageJ/Fiji 1.46 software, the ratio of the area occupied by the muscle to total area of the lesion showed a 7.91% increase in the cell group compared with the control group.<br><br>CONCLUSION: The results of the current study show that injection of hADSCs during repair surgery for fecal incontinence may cause replacement of fibrous tissue, which acts as a mechanical support to muscle tissue with contractile function. This is a key point in treatment of fecal incontinence especially in the long term and may be a major step forward.<br><br>TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT2016022826316N2 . Retrospectively registered 7 May 2016.}, }
@article {pmid28220514, year = {2017}, author = {Jiang, ZD and Ajami, NJ and Petrosino, JF and Jun, G and Hanis, CL and Shah, M and Hochman, L and Ankoma-Sey, V and DuPont, AW and Wong, MC and Alexander, A and Ke, S and DuPont, HL}, title = {Randomised clinical trial: faecal microbiota transplantation for recurrent Clostridum difficile infection - fresh, or frozen, or lyophilised microbiota from a small pool of healthy donors delivered by colonoscopy.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {45}, number = {7}, pages = {899-908}, doi = {10.1111/apt.13969}, pmid = {28220514}, issn = {1365-2036}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile ; Clostridium Infections/*therapy ; Colonoscopy ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Freeze Drying ; Freezing ; Humans ; Male ; Microbiota/genetics ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Recurrence ; Specimen Handling ; Tissue Donors ; Young Adult ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has become routine in managing recurrent C. difficile infection (CDI) refractory to antibiotics.<br><br>AIM: To compare clinical response and improvements in colonic microbiota diversity in subjects with recurrent CDI using different donor product.<br><br>METHODS: Seventy-two subjects with &#x2265;3 bouts of CDI were randomised in a double-blind study to receive fresh, frozen or lyophilised FMT product via colonoscopy from 50 g of stool per treatment from eight healthy donors. Recipients provided stools pre- and 7, 14 and 30 days post-FMT for C. difficile toxin and, in a subset, microbiome composition by 16S rRNA gene profiling.<br><br>RESULTS: Overall resolution of CDI was 87% during 2 months of follow-up after FMT. Stool samples before FMT had significantly decreased bacterial diversity with a high proportion of Proteobacteria compared to donors. Cure rates were highest for the group receiving fresh product seen in 25/25 (100%), lowest for the lyophilised product 16/23 (78%; P = 0.022 vs. fresh and 0.255 vs. frozen) and intermediate for frozen product 20/24 (P = 0.233 vs. fresh). Microbial diversity was reconstituted by day 7 in the subjects receiving fresh or frozen product. Improvement in diversity was seen by day 7 in those randomised to lyophilised material with reconstitution by 30 days.<br><br>CONCLUSIONS: Comparative efficacy in faecal microbiota transplantation was observed in subjects receiving fresh or frozen faecal product from the same donors. The lyophilised product had a slightly lowered efficacy compared with fresh product, but it resembled other treatments in microbial restoration 1 month after faecal microbiota transplantation.}, }
@article {pmid28214091, year = {2017}, author = {Paramsothy, S and Kamm, MA and Kaakoush, NO and Walsh, AJ and van den Bogaerde, J and Samuel, D and Leong, RWL and Connor, S and Ng, W and Paramsothy, R and Xuan, W and Lin, E and Mitchell, HM and Borody, TJ}, title = {Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial.}, journal = {Lancet (London, England)}, volume = {389}, number = {10075}, pages = {1218-1228}, doi = {10.1016/S0140-6736(17)30182-4}, pmid = {28214091}, issn = {1474-547X}, mesh = {Adult ; Colitis, Ulcerative/microbiology/*therapy ; Colonoscopy ; Double-Blind Method ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Remission Induction ; Severity of Illness Index ; Tissue Donors ; }, abstract = {BACKGROUND: The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis.<br><br>METHODS: We conducted a multicentre, double-blind, randomised, placebo-controlled trial at three hospitals in Australia. We randomly allocated patients with active ulcerative colitis (Mayo score 4-10) in a 1:1 ratio, using a pre-established randomisation list, to either faecal microbiota transplantation or placebo colonoscopic infusion, followed by enemas 5 days per week for 8 weeks. Patients, treating clinicians, and other study staff were unaware of the assigned treatment. Faecal microbiota transplantation enemas were each derived from between three and seven unrelated donors. The primary outcome was steroid-free clinical remission with endoscopic remission or response (Mayo score &#x2264;2, all subscores &#x2264;1, and &#x2265;1 point reduction in endoscopy subscore) at week 8. Analysis was by modified intention-to-treat and included all patients receiving one study dose. We performed 16S rRNA stool analysis to assess associated microbial changes. This trial is registered with ClinicalTrials.gov, number NCT01896635. The trial has ended; this report presents the final analysis.<br><br>FINDINGS: From November, 2013, to May, 2015, 85 patients were enrolled to our trial, of whom 42 were randomly assigned faecal microbiota transplantation and 43 were allocated placebo. One patient assigned faecal microbiota transplantation and three allocated placebo did not receive study treatment and were excluded from the analysis. The primary outcome was achieved in 11 (27%) of 41 patients allocated faecal microbiota transplantation versus three (8%) of 40 who were assigned placebo (risk ratio 3&#xb7;6, 95% CI 1&#xb7;1-11&#xb7;9; p=0&#xb7;021). Adverse events were reported by 32 (78%) of 41 patients allocated faecal microbiota transplantation and 33 (83%) of 40 who were assigned placebo; most were self-limiting gastrointestinal complaints, with no significant difference in number or type of adverse events between treatment groups. Serious adverse events occurred in two patients assigned faecal microbiota transplantation and in one allocated placebo. Microbial diversity increased with and persisted after faecal microbiota transplantation. Several bacterial taxa were associated with clinical outcome; in particular, the presence of Fusobacterium spp was associated with lack of remission.<br><br>INTERPRETATION: Intensive-dosing, multidonor, faecal microbiota transplantation induces clinical remission and endoscopic improvement in active ulcerative colitis and is associated with distinct microbial changes that relate to outcome. Faecal microbiota transplantation is, thus, a promising new therapeutic option for ulcerative colitis. Future work should focus on precisely defining the optimum treatment intensity and the role of donor-recipient matching based on microbial profiles.<br><br>FUNDING: Broad Medical Research Program, Gastroenterological Society of Australia, Mount Sinai (New York) SUCCESS fund, University of New South Wales.}, }
@article {pmid28202372, year = {2017}, author = {Parashar, A and Udayabanu, M}, title = {Gut microbiota: Implications in Parkinson's disease.}, journal = {Parkinsonism &amp; related disorders}, volume = {38}, number = {}, pages = {1-7}, pmid = {28202372}, issn = {1873-5126}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Cognition/drug effects ; *Gastrointestinal Microbiome/drug effects ; Humans ; Parkinson Disease/*microbiology/*physiopathology ; Probiotics/therapeutic use ; }, abstract = {Gut microbiota (GM) can influence various neurological outcomes, like cognition, learning, and memory. Commensal GM modulates brain development and behavior and has been implicated in several neurological disorders like Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, anxiety, stress and much more. A recent study has shown that Parkinson's disease patients suffer from GM dysbiosis, but whether it is a cause or an effect is yet to be understood. In this review, we try to connect the dots between GM and PD pathology using direct and indirect evidence.}, }
@article {pmid28196423, year = {2017}, author = {Ponte, A and Pinho, R and Mota, M}, title = {Fecal microbiota transplantation: is there a role in the eradication of carbapenem-resistant Klebsiella pneumoniae intestinal carriage?.}, journal = {Revista espanola de enfermedades digestivas}, volume = {109}, number = {5}, pages = {392}, doi = {10.17235/reed.2017.4425/2016}, pmid = {28196423}, issn = {1130-0108}, mesh = {Aged ; Carbapenem-Resistant Enterobacteriaceae/*isolation &amp; purification ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/complications/diagnosis/therapy ; Coinfection/diagnosis/therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Humans ; Klebsiella Infections/complications/diagnosis/*therapy ; Klebsiella pneumoniae/*isolation &amp; purification ; }, abstract = {The authors present the case of a 66-year-old woman with four hospitalizations due to recurrent Clostridium difficile infection (CDI) non responsive to vancomycin and fidaxomicin. Furthermore, intestinal colonization with carbapenem-resistant Klebsiella pneumoniae (CRKP) was identified after a positive stool culture in a screening routinely performed in our center in patients recently hospitalized.}, }
@article {pmid28195180, year = {2017}, author = {Staley, C and Hamilton, MJ and Vaughn, BP and Graiziger, CT and Newman, KM and Kabage, AJ and Sadowsky, MJ and Khoruts, A}, title = {Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study.}, journal = {The American journal of gastroenterology}, volume = {112}, number = {6}, pages = {940-947}, pmid = {28195180}, issn = {1572-0241}, support = {L30 DK099831/DK/NIDDK NIH HHS/United States ; R21 AI114722/AI/NIAID NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Animals ; Bacteroidetes/isolation &amp; purification ; Capsules ; *Clostridioides difficile ; Cohort Studies ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/chemistry/*microbiology ; Female ; Firmicutes/isolation &amp; purification ; Freeze Drying/methods ; Humans ; Male ; Mice ; *Microbial Viability ; Middle Aged ; Proteobacteria/isolation &amp; purification ; RNA, Ribosomal, 16S/*analysis ; Recurrence ; }, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is increasingly being used for treatment of recurrent Clostridium difficile infection (R-CDI) that cannot be cured with antibiotics alone. In addition, FMT is being investigated for a variety of indications where restoration or restructuring of the gut microbial community is hypothesized to be beneficial. We sought to develop a stable, freeze-dried encapsulated preparation of standardized fecal microbiota that can be used for FMT with ease and convenience in clinical practice and research.<br><br>METHODS: We systematically developed a lyophilization protocol that preserved the viability of bacteria across the taxonomic spectrum found in fecal microbiota and yielded physicochemical properties that enabled consistent encapsulation. We also treated a cohort of R-CDI patients with a range of doses of encapsulated microbiota and analyzed the associated changes in the fecal microbiome of the recipients.<br><br>RESULTS: The optimized lyophilized preparation satisfied all our preset goals for physicochemical properties, encapsulation ease, stability at different temperatures, and microbiota viability in vitro and in vivo (germ-free mice). The capsule treatment was administered to 49 patients. Overall, 43/49 (88%) of patients achieved a clinical success, defined as no recurrence of CDI over 2 months. Analysis of the fecal microbiome demonstrated near normalization of the fecal microbial community by 1 month following FMT treatment. The simplest protocol using the lowest dose (2.1-2.5 &#xd7; 10[11] bacteria in 2-3 capsules) without any colon purgative performed equally well in terms of clinical outcomes and microbiota engraftment.<br><br>CONCLUSIONS: A single administration of encapsulated, freeze-dried fecal microbiota from a healthy donor was highly successful in treating antibiotic-refractory R-CDI syndrome.}, }
@article {pmid28195066, year = {2016}, author = {Konturek, PC and Koziel, J and Dieterich, W and Haziri, D and Wirtz, S and Glowczyk, I and Konturek, K and Neurath, MF and Zopf, Y}, title = {Successful therapy of Clostridium difficile infection with fecal microbiota transplantation.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {67}, number = {6}, pages = {859-866}, pmid = {28195066}, issn = {1899-1505}, mesh = {Aged ; Anti-Bacterial Agents/administration &amp; dosage ; C-Reactive Protein/metabolism ; Clostridioides difficile/*drug effects ; Clostridium Infections/*microbiology/*therapy ; Colonoscopy/methods ; Diarrhea/microbiology/therapy ; Enterocolitis, Pseudomembranous/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/metabolism/microbiology/therapy ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Male ; Treatment Outcome ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea and represents an important burden for healthcare worldwide. Symptoms of severe CDI include watery, foul-smelling diarrhea, peripheral leucocytosis, increased C-reactive protein (CRP), acute renal failure, hypotension and pseudomembranous colitis. Recent studies indicate that the main cause of CDI is dysbiosis, an imbalance in the normal gut microbiota. The restoration of a healthy gut microbiota composition via fecal microbiota transplantation (FMT) recently became more popular. The aim of the present study was to assess the effect of FMT on the healing of CDI and to analyze the changes in the level of pro-inflammatory markers (C-reactive protein, fecal calprotectin) and pro-inflammatory cytokines. Eighteen patients with CDI were included in our study (6 males and 12 females) with recurrent and/or severe CDI. The FMT was performed in 17 patients using colonoscopy, including 16 patients receiving a one-time FMT and 1 patient who needed 2 additional FMTs. One patient was treated with a single round of FMT using push-and-pull enteroscopy. In all CDI patients, before and 3 weeks after FMT, the following parameters were analyzed: C-reactive protein, fecal calprotectin, and plasma interleukin (IL)-6, IL-8 and IL-12, and tumor necrosis factor-alpha (TNF-α). In addition, the plasma level of LL-37, a cathelicidine peptide was assessed by fluorescence-activated cell sorting (FACS) before and 3 months after FMT. Finally, in 7 patients a microbiome analysis was performed by sequencing of 16SrRNA in stool probes obtained before and 3 weeks after FMT. The healing rate of CDI was 94%. In all successfully treated patients no recurrent CDI was observed during follow-up (16 months). The serum level of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8 and IL-12) significantly decreased after FMT. Similarly, CRP and fecal calprotectin normalized after FMT. 3 months after FMT a significant increase of LL-37 in the plasma of successfully treated patients was monitored. The sequencing analysis demonstrated an elevated abundance of beneficial bacterial species such as Lactobacillaceae, Ruminococcaceae, Desulfovibrionaceae, Sutterellaceae and Porphyromonodacea after FMT. No serious side effects were observed. We concluded that FMT represented a very effective and safe treatment of recurrent and/or severe CDI and led to favorable shifts in the composition of gut microbiome.}, }
@article {pmid28192102, year = {2017}, author = {Bouter, KE and van Raalte, DH and Groen, AK and Nieuwdorp, M}, title = {Role of the Gut Microbiome in the Pathogenesis of Obesity and Obesity-Related Metabolic Dysfunction.}, journal = {Gastroenterology}, volume = {152}, number = {7}, pages = {1671-1678}, doi = {10.1053/j.gastro.2016.12.048}, pmid = {28192102}, issn = {1528-0012}, mesh = {Animals ; Bacterial Translocation ; Diabetes Mellitus, Type 2/prevention &amp; control/*therapy ; Diet ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Immunity, Innate ; Obesity/etiology/*physiopathology/prevention &amp; control/*therapy ; }, abstract = {The potential role of intestinal microbiota in the etiology of various human diseases has attracted massive attention in the last decade. As such, the intestinal microbiota has been advanced as an important contributor in the development of obesity and obesity-related metabolic dysfunctions, amongst others. Experiments in animal models have produced evidence for a causal role of intestinal microbiota in the etiology of obesity and insulin resistance. However, with a few exceptions, such causal relation is lacking for humans and most publications merely report associations between intestinal microbial composition and metabolic disorders such as obesity and type 2 diabetes. Thus, the reciprocal relationship between the bacteria and these metabolic disorders remains a matter of debate. The main objective of this review is to critically assess the driving role of intestinal microbe composition in the etiology, prevention, and treatment of obesity and obesity-related metabolic dysfunction, including type 2 diabetes.}, }
@article {pmid28187526, year = {2017}, author = {Cao, H and Xu, M and Dong, W and Deng, B and Wang, S and Zhang, Y and Wang, S and Luo, S and Wang, W and Qi, Y and Gao, J and Cao, X and Yan, F and Wang, B}, title = {Secondary bile acid-induced dysbiosis promotes intestinal carcinogenesis.}, journal = {International journal of cancer}, volume = {140}, number = {11}, pages = {2545-2556}, doi = {10.1002/ijc.30643}, pmid = {28187526}, issn = {1097-0215}, mesh = {Animals ; Bile Acids and Salts/*adverse effects ; Carcinogenesis/*chemically induced/pathology ; Deoxycholic Acid/adverse effects ; Dysbiosis/*chemically induced/microbiology/pathology ; Feces/microbiology ; Inflammation/microbiology/pathology ; Intestines/microbiology/*pathology ; Mice ; Mice, Inbred C57BL ; Microbiota/drug effects ; Wnt Signaling Pathway/drug effects ; beta Catenin/metabolism ; }, abstract = {The gut microbiota plays an important role in maintaining intestinal homeostasis. Dysbiosis is associated with intestinal tumorigenesis. Deoxycholic acid (DCA), a secondary bile acid increased by a western diet, correlates with intestinal carcinogenesis. However, evidence relating bile acids, intestinal microbiota and tumorigenesis are limited. In our study, we investigated the effect of DCA on induction of intestinal dysbiosis and its roles in intestinal carcinogenesis. Alteration of the composition of the intestinal microbiota was induced in DCA-treated APC[min/+] mice, which was accompanied by impaired intestinal barrier, gut low grade inflammation and tumor progression. The transfer of fecal microbiota from DCA-treated mice to another group of Apc[min/+] mice increased tumor multiplicity, induced inflammation and recruited M2 phenotype tumor-associated macrophages. Importantly, the fecal microbiota transplantation activated the tumor-associated Wnt/β-catenin signaling pathway. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block DCA-induced intestinal carcinogenesis, further suggesting the role of dysbiosis in tumor development. Our study demonstrated that alteration of the microbial community induced by DCA promoted intestinal carcinogenesis.}, }
@article {pmid28181378, year = {2017}, author = {Mege, D and Meurette, G and Vitton, V and Leroi, AM and Bridoux, V and Zerbib, P and Sielezneff, I and , }, title = {Sacral nerve stimulation can alleviate symptoms of bowel dysfunction after colorectal resections.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {19}, number = {8}, pages = {756-763}, doi = {10.1111/codi.13624}, pmid = {28181378}, issn = {1463-1318}, mesh = {Adult ; Aged ; Anastomosis, Surgical/adverse effects ; Colectomy/*adverse effects ; Colon/surgery ; Colonic Diseases, Functional/etiology/*therapy ; Female ; Humans ; Intention to Treat Analysis ; *Lumbosacral Plexus ; Male ; Middle Aged ; *Postoperative Complications ; Rectum/surgery ; Transcutaneous Electric Nerve Stimulation/*methods ; Treatment Outcome ; Young Adult ; }, abstract = {AIM: Poor functional results, such as faecal incontinence (FI), low anterior resection syndrome (LARS) or high stool frequency, can occur after colorectal resections, including proctocolectomy with ileal pouch-anal anastomosis (IPAA), rectal resection and left hemicolectomy. Management of such patients is problematic, and some case reports have demonstrated the effectiveness of sacral nerve stimulation (SNS) in these situations. Our aim was to analyse the effectiveness of SNS on poor functional results and on quality of life in patients after treatment with different types of colorectal resection.<br><br>METHOD: At five university hospitals from 2006 to 2014, patients with poor functional results after rectal resection, IPAA or left hemicolectomy underwent a staged SNS implant procedure. Failure was defined by the absence or insufficient improvement (<&#xa0;50%) of FI episodes.<br><br>RESULTS: SNS for bowel dysfunction was performed in 16 patients after rectal resection with coloanal anastomosis, left hemicolectomy with colorectal anastomosis or IPAA. Two (13%) cases of primary failure were observed after the percutaneous stimulation test. Median frequency of stool, FI episodes and urgency were significantly improved in 14 patients. Wexner and LARS scores were also significantly improved for 14 patients. When we compared results according to the type of colorectal surgery (IPAA, rectal resection or left hemicolectomy), median frequencies of stool and urgency, Wexner and LARS scores were still significantly improved. Overall success rate was 75% (12/16 patients) in intention-to-treat analysis and 86% (12/14 patients with permanent electrode) in per-protocol analysis.<br><br>CONCLUSION: SNS seems to improve bowel dysfunction following rectal resection, left hemicolectomy or IPAA.}, }
@article {pmid28181098, year = {2017}, author = {Anand, R and Song, Y and Garg, S and Girotra, M and Sinha, A and Sivaraman, A and Phillips, L and Dutta, SK}, title = {Effect of Aging on the Composition of Fecal Microbiota in Donors for FMT and Its Impact on Clinical Outcomes.}, journal = {Digestive diseases and sciences}, volume = {62}, number = {4}, pages = {1002-1008}, pmid = {28181098}, issn = {1573-2568}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aging/*physiology ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/diagnosis/*therapy ; Fecal Microbiota Transplantation/*trends ; Feces/*microbiology ; Female ; Follow-Up Studies ; Humans ; *Living Donors ; Male ; Microbiota/*physiology ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is emerging as an effective therapy for the treatment of recurrent Clostridium difficile infection (RCDI). Selecting an appropriate donor is vital to the success of FMT. However, the relationship between age of donors and the efficacy of FMT has not been examined to date. The aim of this study was to examine the effect of age of healthy donors on their fecal microbiota and assess the impact of these changes on the clinical efficacy of FMT.<br><br>MATERIALS AND METHODS: This IRB-approved prospective study enrolled donors who were deemed healthy for FMT after careful detailed screening for infectious diseases per institutional protocol. The study was conducted between January 2011 and October 2014. Fecal samples were processed and analyzed using 16S rRNA gene amplicon sequencing. Differences in relative abundance and diversity of the donor fecal microbiota were analyzed in donors above and below 60&#xa0;years of age. Effect of fecal microbiota from donors of different age groups on the efficacy of FMT was also evaluated.<br><br>RESULTS: Twenty-eight healthy human subjects from ages 20-82&#xa0;years were enrolled as donors for FMT. All patients receiving FMT from their respective donors had resolution of RCDI symptoms and had a negative C. difficile toxin test 4-12&#xa0;weeks after FMT. Genomic analysis showed that the relative abundance of phylum Actinobacteria and family Bifidobacteriaceae was reduced in the donors &#x2265;60&#xa0;years of age (p&#xa0;<&#xa0;0.05). However, Bacteroidetes-to-Fermicutes ratio did not demonstrate a significant change between the two groups. Furthermore, microbial diversity did not change significantly with advancing age.<br><br>CONCLUSION: These observations suggest that aging in healthy donors is associated with compositional alterations in the fecal microbiome without change in the overall microbial diversity. These changes do not seem to affect the clinical efficacy of FMT in RCDI patients over 12&#xa0;months.}, }
@article {pmid28178876, year = {2018}, author = {Olesen, SW and Gurry, T and Alm, EJ}, title = {Designing fecal microbiota transplant trials that account for differences in donor stool efficacy.}, journal = {Statistical methods in medical research}, volume = {27}, number = {10}, pages = {2906-2917}, doi = {10.1177/0962280216688502}, pmid = {28178876}, issn = {1477-0334}, mesh = {Bayes Theorem ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*surgery ; *Fecal Microbiota Transplantation ; Humans ; *Research Design ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation is a highly effective intervention for patients suffering from recurrent Clostridium difficile, a common hospital-acquired infection. Fecal microbiota transplantation's success as a therapy for C. difficile has inspired interest in performing clinical trials that experiment with fecal microbiota transplantation as a therapy for other conditions like inflammatory bowel disease, obesity, diabetes, and Parkinson's disease. Results from clinical trials that use fecal microbiota transplantation to treat inflammatory bowel disease suggest that, for at least one condition beyond C. difficile, most fecal microbiota transplantation donors produce stool that is not efficacious. The optimal strategies for identifying and using efficacious donors have not been investigated. We therefore examined the optimal Bayesian response-adaptive strategy for allocating patients to donors and formulated a computationally tractable myopic heuristic. This heuristic computes the probability that a donor is efficacious by updating prior expectations about the efficacy of fecal microbiota transplantation, the placebo rate, and the fraction of donors that produce efficacious stool. In simulations designed to mimic a recent fecal microbiota transplantation clinical trial, for which traditional power calculations predict [Formula: see text] statistical power, we found that accounting for differences in donor stool efficacy reduced the predicted statistical power to [Formula: see text]. For these simulations, using the heuristic Bayesian allocation strategy more than quadrupled the statistical power to [Formula: see text]. We use the results of similar simulations to make recommendations about the number of patients, the number of donors, and the choice of clinical endpoint that clinical trials should use to optimize their ability to detect if fecal microbiota transplantation is effective for treating a condition.}, }
@article {pmid28178052, year = {2017}, author = {Saeedi, BJ and Morison, DG and Kraft, CS and Dhere, T}, title = {Fecal Microbiota Transplant for Clostridium difficile Infection in a Pregnant Patient.}, journal = {Obstetrics and gynecology}, volume = {129}, number = {3}, pages = {507-509}, doi = {10.1097/AOG.0000000000001911}, pmid = {28178052}, issn = {1873-233X}, mesh = {Adult ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Pregnancy ; Pregnancy Complications, Infectious/*therapy ; Recurrence ; }, abstract = {BACKGROUND: Clostridium difficile infection has been associated with negative outcomes in the general population and in pregnant patients. Fecal microbiota transplant has become the standard for treatment of recurrent as well as refractory C difficile infection.<br><br>CASE: We present a case of a 28-year-old pregnant woman who presented with recurrent C difficile infection despite treatment with vancomycin and fidaxomicin and underwent a successful fecal microbiota transplant through colonoscopy at 18 weeks of gestation. She no longer required antibiotics for the remainder of her pregnancy to treat C difficile and had a term vaginal delivery at 39 weeks of gestation.<br><br>CONCLUSION: Our pregnant patient tolerated and responded to a fecal microbiota transplant for treatment of recurrent C difficile infection. Future large-scale studies are needed to determine the efficacy, safety, and long-term effects of manipulating the microbiome in pregnant patients and the neonates.}, }
@article {pmid28176463, year = {2017}, author = {Avery, RK and Lonze, BE and Kraus, ES and Marr, KA and Montgomery, RA}, title = {Severe chronic norovirus diarrheal disease in transplant recipients: Clinical features of an under-recognized syndrome.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {19}, number = {2}, pages = {}, doi = {10.1111/tid.12674}, pmid = {28176463}, issn = {1399-3062}, mesh = {Adult ; Aged ; Caliciviridae Infections/epidemiology/*virology ; Chronic Disease ; Diarrhea/epidemiology/*virology ; Enteritis/epidemiology/*virology ; Feces/virology ; Female ; Humans ; Immunocompromised Host ; Immunosuppression Therapy/*adverse effects ; Incidence ; Male ; Middle Aged ; Norovirus/*isolation &amp; purification ; RNA, Viral/isolation &amp; purification ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Syndrome ; Transplant Recipients ; Transplantation/*adverse effects ; Young Adult ; }, abstract = {BACKGROUND: Norovirus (NV) infection has been reported as a cause of severe chronic diarrhea in transplant recipients, but this entity remains under-recognized in clinical practice, leading to diagnostic delays. Transplant clinicians should become familiar with this syndrome in order to facilitate early detection and management.<br><br>METHODS: Demographic, clinical, and outcomes variables were summarized from a series of transplant recipients with positive stool NV reverse transcription polymerase chain reaction (RT-PCR) assays at Johns Hopkins in 2013-2014. Factors associated with longer duration of symptoms were compared using random forest analysis.<br><br>RESULTS: Thirty-one of 193 (16%) transplant recipients who were tested for NV had positive stool RT-PCRs. Symptoms included diarrhea (100%), nausea/vomiting (58%), abdominal pain (52%), and wasting (35%). Acute kidney injury occurred in 23%, and persisted in 21% after 6&#xa0;months. Median duration of diarrheal symptoms was 4&#xa0;months (range, <1-20) and 11/31 (35.4%) patients had relapses after improvement. Wasting, incompatible kidney transplant status, and plasmapheresis were associated with longer diarrhea durations. Treatments included nitazoxanide (in 74%), reduction of immunosuppression (58%), and intravenous immunoglobulin (32%). Six patients died, but no deaths were attributed to NV.<br><br>CONCLUSIONS: It is important for clinicians to recognize that NV can cause severe chronic diarrhea in transplant recipients. In this series, receipt of a human leukocyte antigen- and/or blood type-incompatible kidney transplant, and plasmapheresis were associated with longer symptom duration.}, }
@article {pmid28174759, year = {2016}, author = {Greenspan, NS}, title = {"Infectious Supercarelessness" in Discussing Antibiotic-Resistant Bacteria.}, journal = {Pathogens &amp; immunity}, volume = {1}, number = {2}, pages = {304-307}, pmid = {28174759}, issn = {2469-2964}, support = {P30 AI036219/AI/NIAID NIH HHS/United States ; }, abstract = {Many bacterial pathogens are exhibiting resistance to increasing numbers of antibiotics making it much more challenging to treat the infections caused by these microbes. In many reports in the media and perhaps even in discussions among physicians and biomedical scientists, these bacteria are frequently referred to as "bugs" with the prefix "super" appended. This terminology has a high potential to elicit unjustified inferences and fails to highlight the broader evolutionary context. Understanding the full range of biological and evolutionary factors that influence the spread and outcomes of infections is critical to formulating effective individual therapies and public health interventions. Therefore, more accurate terminology should be used to refer these multidrug-resistant bacteria.}, }
@article {pmid28170133, year = {2017}, author = {Trinh, SA and Echenique, IA and Penugonda, S and Angarone, MP}, title = {Optimal strategies for the diagnosis of community-onset diarrhea in solid organ transplant recipients: Less is more.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {19}, number = {2}, pages = {}, pmid = {28170133}, issn = {1399-3062}, support = {T32 AI095207/AI/NIAID NIH HHS/United States ; UL1 RR025741/RR/NCRR NIH HHS/United States ; UL1 TR000150/TR/NCATS NIH HHS/United States ; }, mesh = {Clostridioides difficile ; Community-Acquired Infections/complications/*diagnosis/microbiology/virology ; Costs and Cost Analysis ; Cytomegalovirus/isolation &amp; purification ; Diagnostic Techniques, Digestive System/*economics/standards ; Diarrhea/complications/*diagnosis/microbiology/virology ; Endoscopy, Gastrointestinal ; Evidence-Based Medicine/*economics/standards ; Feces/microbiology/parasitology/virology ; Foodborne Diseases/diagnosis/microbiology ; Graft Rejection/*complications/mortality ; Hospitalization/*economics ; Humans ; Immunoenzyme Techniques/economics ; Norovirus/isolation &amp; purification ; Organ Transplantation/*adverse effects/mortality ; Polymerase Chain Reaction/economics ; Practice Guidelines as Topic ; Retrospective Studies ; Transplant Recipients ; Transplantation, Homologous/adverse effects ; }, abstract = {BACKGROUND: Diarrhea, a common complication after solid organ transplant (SOT), is associated with allograft failure and death. No evidence-based guidelines exist for the evaluation of diarrhea in SOT recipients. We performed a cost analysis to derive a testing algorithm for the diagnosis of community-onset diarrhea that minimizes costs without compromising diagnostic yields.<br><br>DESIGN: A cost analysis was performed on a retrospective cohort of 422 SOT admissions for community-onset diarrhea over an 18-month period. A stepwise testing model was applied on a population level to assess test costs relative to diagnostic yields.<br><br>RESULTS: Over an 18-month period, 1564 diagnostic tests were performed and 127 (8.1%) returned positive. Diagnostic testing accounted for $95 625 of hospital costs. The tests with the lowest cost per decrease in the false-omission rate (FOR) were stool Clostridium difficile polymerase chain reaction (PCR) ($156), serum cytomegalovirus quantitative PCR ($1529), stool norovirus (NV) PCR ($4673), and stool culture ($6804). A time-to-event analysis found no significant difference in the length of hospital stay between patients with and without NV testing (P=.520).<br><br>CONCLUSIONS: A stepwise testing strategy can reduce costs without compromising diagnostic yields. In the first-stage testing, we recommend assessment for C.&#xa0;difficile, cytomegalovirus, and food-borne bacterial pathogens. For persistent diarrheal episodes, second-stage evaluation should include stool NV PCR, Giardia/Cryptosporidium enzyme immunoassay, stool ova and parasite, reductions in immunosuppressive therapy, and possibly endoscopy. Although NV testing had a relatively low cost per FOR, we recommend NV testing during second-stage evaluation, as an NV diagnosis may not lead to changes in clinical management or further reductions in length of hospital stay.}, }
@article {pmid28164849, year = {2017}, author = {Vindigni, SM and Surawicz, CM}, title = {Fecal Microbiota Transplantation.}, journal = {Gastroenterology clinics of North America}, volume = {46}, number = {1}, pages = {171-185}, doi = {10.1016/j.gtc.2016.09.012}, pmid = {28164849}, issn = {1558-1942}, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; Donor Selection ; Dysbiosis/*therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Humans ; Inflammatory Bowel Diseases/therapy ; Informed Consent ; *Patient Selection ; }, abstract = {Fecal microbiota transplantation (FMT) is the transfer of stool from a healthy donor into the colon of a patient whose disease is a result of an altered microbiome, with the goal of restoring the normal microbiota and thus curing the disease. The most effective and well-studied indication for FMT is recurrent Clostridium difficile infection. At this time, there is insufficient evidence to recommend FMT for other gastrointestinal diseases, but studies are under way. There is also insufficient evidence to recommend FMT for nongastrointestinal diseases at this time. The field is rapidly emerging.}, }
@article {pmid28164847, year = {2017}, author = {Sheehan, D and Shanahan, F}, title = {The Gut Microbiota in Inflammatory Bowel Disease.}, journal = {Gastroenterology clinics of North America}, volume = {46}, number = {1}, pages = {143-154}, doi = {10.1016/j.gtc.2016.09.011}, pmid = {28164847}, issn = {1558-1942}, mesh = {*Environmental Exposure ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/virology ; Humans ; Inflammatory Bowel Diseases/genetics/immunology/*microbiology/therapy ; }, abstract = {Genes, bacteria, and immunity contribute to the pathogenesis of inflammatory bowel disease. Most genetic risk relates to defective sensing of microbes and their metabolites or defective regulation of the host response to the microbiota. Because the composition of the microbiota shapes the developing immune system and is determined in early life, the prospect of therapeutic manipulation of the microbiota in adulthood after the onset of disease is questionable. However, the microbiota may be a marker of risk and a modifier of disease activity and a contributor to extraintestinal manifestations and associations in some patients with inflammatory bowel disease.}, }
@article {pmid28158664, year = {2017}, author = {Jansen, JW}, title = {Fecal Microbiota Transplant vs Oral Vancomycin Taper: Important Undiscussed Limitations.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {64}, number = {9}, pages = {1292-1293}, doi = {10.1093/cid/cix093}, pmid = {28158664}, issn = {1537-6591}, mesh = {*Clostridioides difficile ; *Fecal Microbiota Transplantation ; Microbiota ; Research Design ; Vancomycin ; }, }
@article {pmid28158498, year = {2017}, author = {Hota, SS and Tomlinson, G and Poutanen, SM}, title = {Reply to Galperine et al and Jansen.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {64}, number = {9}, pages = {1293-1295}, doi = {10.1093/cid/cix094}, pmid = {28158498}, issn = {1537-6591}, mesh = {Administration, Oral ; *Clostridioides difficile ; *Fecal Microbiota Transplantation ; Research Design ; Vancomycin ; }, }
@article {pmid28158478, year = {2017}, author = {Galpérine, T and Sokol, H and Guery, B}, title = {Fecal Microbiota Transplantation: Do We Need Harmonization?.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {64}, number = {9}, pages = {1292}, doi = {10.1093/cid/cix092}, pmid = {28158478}, issn = {1537-6591}, mesh = {Administration, Oral ; *Clostridioides difficile ; *Fecal Microbiota Transplantation ; Research Design ; Vancomycin ; }, }
@article {pmid28158276, year = {2017}, author = {Tian, H and Ge, X and Nie, Y and Yang, L and Ding, C and McFarland, LV and Zhang, X and Chen, Q and Gong, J and Li, N}, title = {Fecal microbiota transplantation in patients with slow-transit constipation: A randomized, clinical trial.}, journal = {PloS one}, volume = {12}, number = {2}, pages = {e0171308}, pmid = {28158276}, issn = {1932-6203}, mesh = {Adult ; Aged ; Constipation/diagnosis/*therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Workflow ; }, abstract = {Fecal microbiota transplantation has been proposed as a therapeutic approach for chronic constipation. This randomized, controlled trial aimed to compare the effects of conventional treatment alone (control) with additional treatment with FMT (intervention) in patients with slow-transit constipation (STC). Adults with STC were randomized to receive intervention or control treatment. The control group received education, behavioral strategies, and oral laxatives. The intervention group was additionally provided 6 days of FMT. The primary endpoint was the clinical cure rate (proportion of patients achieving a mean of ≥ three complete spontaneous bowel movements [CSBMs] per week]. Secondary outcomes and safety parameters were assessed throughout the study. Sixty patients were randomized to either conventional treatment alone (n = 30) or FMT (n = 30) through a nasointestinal tube. There were significant differences between the intervention group and control group in the clinical improvement rate (intention-to-treat [ITT]: 53.3% vs. 20.0%, P = 0.009), clinical cure rate (ITT: 36.7% vs. 13.3%, P = 0.04), mean number of CSBMs per week (ITT: 3.2 ± 1.4 vs. 2.1 ± 1.2, P = 0.001), and the Wexner constipation score (ITT: 8.6 ± 1.5 vs. 12.7 ± 2.5, P < 0.00001). Compared with the control group, the intervention group showed better results in the stool consistency score (ITT: 3.9 vs. 2.4, P < 0.00001) and colonic transit time (ITT: 58.5 vs. 73.6 h, P < 0.00001). The intervention group had more treatment-related adverse events than did the control group (50 vs. 4 cases). FMT was significantly more effective (30% higher cure rate) for treatment of STC than conventional treatment. No serious adverse events were observed.}, }
@article {pmid28157682, year = {2016}, author = {}, title = {Fecal microbiota transplantation for aGVHD of the gut.}, journal = {Blood}, volume = {128}, number = {16}, pages = {2107}, doi = {10.1182/blood-2016-09-738062}, pmid = {28157682}, issn = {1528-0020}, }
@article {pmid28154388, year = {2017}, author = {Bodiwala, V and Skole, K}, title = {Possible Alternative Predictors of Failure of Fecal Microbiota Transplant for Therapy of Recurrent C difficile Infection.}, journal = {The American journal of gastroenterology}, volume = {112}, number = {2}, pages = {390-391}, pmid = {28154388}, issn = {1572-0241}, mesh = {Clostridioides difficile ; Clostridium Infections ; *Enterocolitis, Pseudomembranous ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Microbiota ; Recurrence ; Treatment Outcome ; }, }
@article {pmid28154090, year = {2017}, author = {Spindelboeck, W and Schulz, E and Uhl, B and Kashofer, K and Aigelsreiter, A and Zinke-Cerwenka, W and Mulabecirovic, A and Kump, PK and Halwachs, B and Gorkiewicz, G and Sill, H and Greinix, H and Högenauer, C and Neumeister, P}, title = {Repeated fecal microbiota transplantations attenuate diarrhea and lead to sustained changes in the fecal microbiota in acute, refractory gastrointestinal graft-versus-host-disease.}, journal = {Haematologica}, volume = {102}, number = {5}, pages = {e210-e213}, pmid = {28154090}, issn = {1592-8721}, mesh = {Combined Modality Therapy ; Diarrhea/etiology/therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Gastrointestinal Diseases/diagnosis/*etiology/physiopathology/*therapy ; Graft vs Host Disease/diagnosis/*etiology/physiopathology/*therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Male ; Middle Aged ; Treatment Outcome ; }, }
@article {pmid28154011, year = {2017}, author = {Yang, M and Fukui, H and Eda, H and Xu, X and Kitayama, Y and Hara, K and Kodani, M and Tomita, T and Oshima, T and Watari, J and Miwa, H}, title = {Involvement of gut microbiota in association between GLP-1/GLP-1 receptor expression and gastrointestinal motility.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {312}, number = {4}, pages = {G367-G373}, doi = {10.1152/ajpgi.00232.2016}, pmid = {28154011}, issn = {1522-1547}, mesh = {Animals ; Exenatide ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Gastrointestinal Motility/drug effects/*physiology ; Gastrointestinal Tract/*microbiology ; Gastrointestinal Transit/drug effects/*physiology ; Glucagon-Like Peptide 1/genetics/*metabolism ; Glucagon-Like Peptide-1 Receptor/genetics/*metabolism ; Mice ; Peptides/pharmacology ; Venoms/pharmacology ; }, abstract = {The microbiota in the gut is known to play a pivotal role in host physiology by interacting with the immune and neuroendocrine systems in gastrointestinal (GI) tissues. Glucagon-like peptide 1 (GLP-1), a gut hormone, is involved in metabolism as well as GI motility. We examined how gut microbiota affects the link between GLP-1/GLP-1 receptor (GLP-1R) expression and motility of the GI tract. Germ-free (GF) mice (6 wk old) were orally administered a fecal bacterial suspension prepared from specific pathogen-free (SPF) mice, and then after fecal transplantation (FT) GI tissues were obtained from the GF mice at various time points. The expression of GLP-1 and its receptor was examined by immunohistochemistry, and gastrointestinal transit time (GITT) was measured by administration of carmine red solution. GLP-1 was expressed in endocrine cells in the colonic mucosa, and GLP-1R was expressed in myenteric neural cells throughout the GI wall. GLP-1R-positive cells throughout the GI wall were significantly fewer in GF mice with FT than in GF mice without gut microbiota reconstitution. GITT was significantly shorter in GF mice with FT than in control GF mice without FT and correlated with the number of GLP-1R-positive cells throughout the GI wall. GITT was significantly longer in GF control mice than in SPF mice. When those mice were treated with GLP-1 agonist extendin4, GITT was significantly longer in the GF mice. The gut microbiota may accelerate or at least modify GI motility while suppressing GLP-1R expression in myenteric neural cells throughout the GI tract.NEW &amp; NOTEWORTHY The gut microbiota has been intensively studied, because it plays a pivotal role in various aspects of host physiology. On the other hand, glucagon-like peptide 1 (GLP-1) plays important roles in metabolism as well as gastrointestinal motility. In the present study, we have suggested that the gut microbiota accelerates gastrointestinal motility while suppressing the expression of GLP-1 receptor in myenteric neural cells throughout the gastrointestinal tract. We believe that this article is very timely and suggestive work.}, }
@article {pmid28147375, year = {2017}, author = {Reinisch, W}, title = {Fecal Microbiota Transplantation in Inflammatory Bowel Disease.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {35}, number = {1-2}, pages = {123-126}, doi = {10.1159/000449092}, pmid = {28147375}, issn = {1421-9875}, mesh = {Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Intestines/microbiology ; Randomized Controlled Trials as Topic ; }, abstract = {The etiology of inflammatory bowel disease (IBD) is unknown, but it is thought to arise from an aberrant immune response to a change in colonic environment in a genetically susceptible individual. The intestinal microbiota are located at the complex interface of the epithelial barrier and are sensitive to changes in environmental factors, such as diets, drugs or smoking and signals derived from the intestinal immune system and the gut-brain axis. In patients with IBD, an imbalance in the structural and/or functional configuration of the intestinal microbiota leading to the disruption of the host-microorganism homeostasis (dysbiosis) has been reproducibly reported. As animal models of IBD require gut bacteria to induce inflammation, it is hypothesized that the dysbiosis observed in patients is not only a surrogate of changes at the intestinal barrier but also a potential cause or at least enhancer of the mucosal inflammatory process. That burgeoning notion has stimulated thoughts to modify the intestinal microbiota and rekindled interest in previous work on the efficacy of antibiotics in patients with IBD. The feasibility and tremendous success of fecal microbiota transplantation (FMT) to treat antibiotic resistant Clostridium difficile has finally paved the way to embark into the unchartered territory of IBD using FMT. Different routes and number of administrations, choices of donors, disease status and permitted therapies might have contributed to mixed results, particularly from the so far published randomized controlled trials. However, microbiome analysis suggests that a durable transplantation of donor bacteria to the host appears feasible and might be associated with a higher likelihood of response. On the other hand, this raises the concern of transplanting not only anti-inflammatory active bacteria and their products, but also not-yet-known dispositions for other diseases including cancer. Attempts are being made to better characterize those components of the microbiome of healthy individuals, which might mediate anti-inflammatory functions and assemble 'synthetic stools' for more standardized treatment approaches.}, }
@article {pmid28143773, year = {2017}, author = {Kelly, CR and Kim, AM and Laine, L and Wu, GD}, title = {The AGA's Fecal Microbiota Transplantation National Registry: An Important Step Toward Understanding Risks and Benefits of Microbiota Therapeutics.}, journal = {Gastroenterology}, volume = {152}, number = {4}, pages = {681-684}, doi = {10.1053/j.gastro.2017.01.028}, pmid = {28143773}, issn = {1528-0012}, mesh = {*Fecal Microbiota Transplantation/adverse effects/methods ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Patient Safety ; *Registries ; Risk Assessment ; Risk Factors ; Treatment Outcome ; United States ; }, }
@article {pmid28143587, year = {2017}, author = {Li, J and Zhao, F and Wang, Y and Chen, J and Tao, J and Tian, G and Wu, S and Liu, W and Cui, Q and Geng, B and Zhang, W and Weldon, R and Auguste, K and Yang, L and Liu, X and Chen, L and Yang, X and Zhu, B and Cai, J}, title = {Gut microbiota dysbiosis contributes to the development of hypertension.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {14}, pmid = {28143587}, issn = {2049-2618}, mesh = {Animals ; Blood Pressure/*physiology ; Cohort Studies ; Dysbiosis ; Essential Hypertension ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Germ-Free Life ; Humans ; Hypertension/*microbiology ; Klebsiella/genetics/isolation &amp; purification ; Male ; Mice ; Mice, Inbred C57BL ; Prehypertension/*microbiology ; Prevotella/genetics/isolation &amp; purification ; Prospective Studies ; }, abstract = {BACKGROUND: Recently, the potential role of gut microbiome in metabolic diseases has been revealed, especially in cardiovascular diseases. Hypertension is one of the most prevalent cardiovascular diseases worldwide, yet whether gut microbiota dysbiosis participates in the development of hypertension remains largely unknown. To investigate this issue, we carried out comprehensive metagenomic and metabolomic analyses in a cohort of 41 healthy controls, 56 subjects with pre-hypertension, 99 individuals with primary hypertension, and performed fecal microbiota transplantation from patients to germ-free mice.<br><br>RESULTS: Compared to the healthy controls, we found dramatically decreased microbial richness and diversity, Prevotella-dominated gut enterotype, distinct metagenomic composition with reduced bacteria associated with healthy status and overgrowth of bacteria such as Prevotella and Klebsiella, and disease-linked microbial function in both pre-hypertensive and hypertensive populations. Unexpectedly, the microbiome characteristic in pre-hypertension group was quite similar to that in hypertension. The metabolism changes of host with pre-hypertension or hypertension were identified to be closely linked to gut microbiome dysbiosis. And a disease classifier based on microbiota and metabolites was constructed to discriminate pre-hypertensive and hypertensive individuals from controls accurately. Furthermore, by fecal transplantation from hypertensive human donors to germ-free mice, elevated blood pressure was observed to be transferrable through microbiota, and the direct influence of gut microbiota on blood pressure of the host was demonstrated.<br><br>CONCLUSIONS: Overall, our results describe a novel causal role of aberrant gut microbiota in contributing to the pathogenesis of hypertension. And the significance of early intervention for pre-hypertension was emphasized.}, }
@article {pmid28140325, year = {2016}, author = {de Clercq, NC and Groen, AK and Romijn, JA and Nieuwdorp, M}, title = {Gut Microbiota in Obesity and Undernutrition.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {7}, number = {6}, pages = {1080-1089}, pmid = {28140325}, issn = {2156-5376}, mesh = {Animals ; *Appetite ; *Energy Intake ; *Energy Metabolism ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism/*microbiology ; Humans ; Malnutrition/*etiology/metabolism/microbiology/therapy ; Obesity/*etiology/metabolism/microbiology/therapy ; Prebiotics ; Probiotics ; }, abstract = {Malnutrition is the result of an inadequate balance between energy intake and energy expenditure that ultimately leads to either obesity or undernutrition. Several factors are associated with the onset and preservation of malnutrition. One of these factors is the gut microbiota, which has been recognized as an important pathophysiologic factor in the development and sustainment of malnutrition. However, to our knowledge, the extent to which the microbiota influences malnutrition has yet to be elucidated. In this review, we summarize the mechanisms via which the gut microbiota may influence energy homeostasis in relation to malnutrition. In addition, we discuss potential therapeutic modalities to ameliorate obesity or undernutrition.}, }
@article {pmid28137431, year = {2017}, author = {McClain, C and Barve, S}, title = {A tale of two institutions.}, journal = {Journal of hepatology}, volume = {66}, number = {4}, pages = {682-684}, pmid = {28137431}, issn = {1600-0641}, support = {P20 GM113226/GM/NIGMS NIH HHS/United States ; U01 AA022618/AA/NIAAA NIH HHS/United States ; P50 AA024337/AA/NIAAA NIH HHS/United States ; R01 AA018869/AA/NIAAA NIH HHS/United States ; R01 AA023681/AA/NIAAA NIH HHS/United States ; U01 AA022489/AA/NIAAA NIH HHS/United States ; R01 AA024405/AA/NIAAA NIH HHS/United States ; U01 AA021893/AA/NIAAA NIH HHS/United States ; U01 AA021901/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol Drinking ; Animals ; *Chemical and Drug Induced Liver Injury ; *Dysbiosis ; *Fecal Microbiota Transplantation ; Mice ; }, }
@article {pmid28134688, year = {2017}, author = {Pearson, JS and Whorwell, PJ}, title = {Progress with treating the microbial dysbiosis associated with irritable bowel syndrome.}, journal = {Current opinion in gastroenterology}, volume = {33}, number = {1}, pages = {21-25}, doi = {10.1097/MOG.0000000000000328}, pmid = {28134688}, issn = {1531-7056}, mesh = {Anti-Bacterial Agents/therapeutic use ; Dietary Supplements ; Dysbiosis/diet therapy/microbiology/*physiopathology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Humans ; Irritable Bowel Syndrome/microbiology/*physiopathology/therapy ; }, abstract = {PURPOSE OF REVIEW: Microbial dysbiosis is receiving increasing attention as possibly being important in the pathophysiology of irritable bowel syndrome. This review will summarize the most recent literature addressing attempts to explore and target the microbiome in patients with irritable bowel syndrome.<br><br>RECENT FINDINGS: Manipulation of the intestinal microbiota in irritable bowel syndrome is receiving increasing attention. Traditionally, dietary manipulation has been utilized. There is now evidence that a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet has not only been able to improve symptoms, but may have an effect on the gut microbiota. Probiotics are a safe and attractive option for the manipulation of the microbiota. There have been a number of well-designed trials examining the efficacy of certain strains of bacteria, and even yeasts are receiving attention. The role of antibiotics remains controversial and it seems likely that their use should currently be limited to those individuals with small intestinal bacterial overgrowth. Interest in the role of faecal microbiota transplantation for the treatment of a number of gastrointestinal conditions has intensified and irritable bowel syndrome is no exception.<br><br>SUMMARY: The manipulation of the microbial dysbiosis is gaining momentum. Further research, however, is required in order to identify the most appropriate treatment option for each individual patient.}, }
@article {pmid28134687, year = {2017}, author = {Malikowski, T and Khanna, S and Pardi, DS}, title = {Fecal microbiota transplantation for gastrointestinal disorders.}, journal = {Current opinion in gastroenterology}, volume = {33}, number = {1}, pages = {8-13}, doi = {10.1097/MOG.0000000000000326}, pmid = {28134687}, issn = {1531-7056}, mesh = {*Fecal Microbiota Transplantation ; Gastrointestinal Diseases/*microbiology/physiopathology/therapy ; Gastrointestinal Microbiome/physiology ; Humans ; Inflammatory Bowel Diseases/microbiology/physiopathology/therapy ; Irritable Bowel Syndrome/microbiology/physiopathology/therapy ; Liver Diseases, Alcoholic/microbiology/physiopathology/therapy ; Non-alcoholic Fatty Liver Disease/microbiology/physiopathology/therapy ; }, abstract = {PURPOSE OF REVIEW: The importance of the gut microbiome in human health is being increasingly recognized. The purpose of this review is to examine the existing literature pertaining to alterations in the gut microbiome and the utility of microbiome restoration therapies in gastrointestinal disorders.<br><br>RECENT FINDINGS: Imbalance and maladaptation of the microbiome, termed dysbiosis, has been associated with several disease states such as irritable bowel syndrome, Clostridium difficile infection, inflammatory bowel diseases, nonalcoholic fatty liver disease, and obesity among others. The possibility of restoration of normal microbiota has become an attractive concept for diseases in which the normal microbiome is perturbed. The rationale of using fecal microbiota transplantation to treat disease has been validated by its successful use in treating recurrent Clostridium difficile infection, which occurs as a result of decreased microbial diversity in the gut, most often in the setting of recent antibiotic treatment. Similar strategies may be applicable to other disorders.<br><br>SUMMARY: Alterations in the gut microbiome are associated with several disorders, and microbiome restoration based therapies such as fecal microbiota transplantation may be an adjunct to conventional treatments but more investigation is needed.}, }
@article {pmid28131442, year = {2017}, author = {Doré, J and Multon, MC and Béhier, JM and , }, title = {The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?.}, journal = {Therapie}, volume = {72}, number = {1}, pages = {21-38}, doi = {10.1016/j.therap.2016.12.007}, pmid = {28131442}, issn = {0040-5957}, mesh = {Clostridioides difficile ; Clostridium Infections/therapy ; Diet ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Oxidative Stress/physiology ; Probiotics/therapeutic use ; }, abstract = {From the moment of birth, each human being builds a microbe-host symbiosis which is key for the preservation of its health and well-being. This personal symbiotic coexistence is the result of progressive enrichments in microorganism diversity through external supplies. This diversity is nowadays massively overthrown by drastic changes related to clinical practice in birth management, environmental exposure, nutrition and healthcare behaviors. The last two generations have been the frame of massive modifications in life and food habits, with people being more and more sedentary, overfed and permeated with drugs and pollutants. We are now able to measure the impact of these changes on the gut microbiota diversity. Concomitantly, these modifications of lifestyle were associated with a dramatic increase in incidence of immune-mediated diseases including metabolic, allergic and inflammatory diseases and most likely neurodegenerative and psychiatric disorders. Microbiota is becoming a hot topic in the scientific community and in the mainstream media. The number of scientific publications increased by up to a factor three over the last five years, with gastrointestinal and metabolic diseases being the most productive areas. In the intellectual property landscape, the patent families on microbiota have more than doubled in the meantime. In parallel, funding either from National Institutes (e.g. from NIH which funds research mainly in the field of allergies, infections, cancer and cardiovascular diseases, from the White House which launched the national microbiome initiative) or by pharmaceutical companies follow the same trend, showing a boost and a strong support in the research field on microbiota. All major health players are investing in microbiome research as shown by the number of deals signed and by funding during 2015. The Giens round table addressed how the medicine of tomorrow, considering human beings as a human-microbe symbiotic supraorganism, could leverage microbiome knowledge and tools. The rationale for our working group has been structured around four domains of innovation that could derive from ongoing efforts in deciphering the interactions between human cells and intestinal microbiome as a central component of human health, namely: (1) development of stratification and monitoring tools; (2) identification of new target and drug discovery, as a part of our supra-genome; (4) exploitation of microbiota as a therapeutic target that can be modulated; (4) and finally as a source of live biotherapeutics and adjuvants. These four streams will exemplify how microbiota has changed the way we consider a wide range of chronic and incurable diseases and the consequences of long-lasting dysbiosis. In-depth microbiota analysis is opening one of the broadest fields of investigation for improving human and animal health and will be a source of major therapeutic innovations for tackling today's medical unmet needs. We thus propose a range of recommendations for basic researchers, care givers as well as for health authorities to gain reliability in microbiome analysis and accelerate discovery processes and their translation into applications for the benefits of the people. Finally, les Ateliers de Giens round table on microbiota benefited from the richness of the French ecosystem. France represents a center of excellence in the microbiota research field, with French institutions as Institut national de la recherche agronomique (INRA [Metagenopolis, Micalis]), Centre national de la recherché scientifique (CNRS), Unité de recherche sur les maladies infectieuses et tropicales émergentes (URMITE), Institut of Cardiometabolism and Nutrition (ICAN), Institut des maladies métaboliques et cardiovasculaires (I2MC), Institut national de la santé et de la recherche médicale (Inserm), Pasteur Institute and Gustave-Roussy being top-players for the number of publications.}, }
@article {pmid28131326, year = {2017}, author = {Ong, GK and Reidy, TJ and Huk, MD and Lane, FR}, title = {Clostridium difficile colitis: A clinical review.}, journal = {American journal of surgery}, volume = {213}, number = {3}, pages = {565-571}, doi = {10.1016/j.amjsurg.2016.10.035}, pmid = {28131326}, issn = {1879-1883}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; Clostridium Infections/diagnosis/epidemiology/*therapy ; Colectomy ; Donor Selection ; Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/microbiology ; Severity of Illness Index ; Therapeutic Irrigation ; }, abstract = {BACKGROUND: Clostridium difficile colitis is an important cause of morbidity and mortality in the surgical patient. In recent years, Clostridium difficile infections have shown marked increases in frequency, severity, and resistance to standard treatment. With urgent operative interventions and novel endoscopic approaches, pseudomembranous colitis is being seen more commonly in surgical practices.<br><br>DATA SOURCES: In this paper, we will review a number of papers from the literature. We will discuss the epidemiology, evaluation and treatment of Clostridium difficile infection. Fulminant colitis may require emergency operation. For the surgical endoscopist, fecal microbiota transplantation restores the gastrointestinal flora, and has been shown to be effective in more than 80% of patients.<br><br>CONCLUSION: Clostridium difficile infection is a major cause of healthcare-related diarrhea leading to increased morbidity and mortality in surgical patients. Increases in failure rates and resistance to current treatments are clinical and economic challenges in the healthcare situation.}, }
@article {pmid28129018, year = {2017}, author = {Woodworth, MH and Carpentieri, C and Sitchenko, KL and Kraft, CS}, title = {Challenges in fecal donor selection and screening for fecal microbiota transplantation: A review.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {225-237}, pmid = {28129018}, issn = {1949-0984}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; }, mesh = {Clostridium Infections/therapy ; *Donor Selection ; Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome/drug effects ; Humans ; Metabolic Diseases/diagnosis/microbiology ; Obesity/diagnosis/microbiology ; United States ; United States Food and Drug Administration ; }, abstract = {Fecal microbiota transplantation is best understood as an effective and inexpensive therapy for recurrent Clostridium difficile infection but fecal donor selection and screening should be periodically revised. Here, we review current recommendations for selection and screening of fecal donors for fecal microbiota transplantation. We recommend considering diabetes mellitus, prior cardiovascular events, and clinical healthcare exposure as fecal donor exclusion criteria until more is known about the association of these conditions with the human gut microbiome. We review the non-bacterial members of the human gut microbiome, associations of the gut microbiome with colorectal malignancies, the human gut resistome and how these may impact future donor screening recommendations. Collaboration between clinicians, clinical laboratory scientists, industry and regulatory agencies will be critically important for continued improvement in donor selection and screening.}, }
@article {pmid28126184, year = {2017}, author = {Zamudio-Tiburcio, &#xc1; and Bermúdez-Ruiz, H and Lezama-Guzmán, HR and Guevara-Ortigoza, MDP and Islas-Solares, E and Sosa-López, FA}, title = {[Breaking paradigms. Intestinal microbiota transplantation: Preliminar report].}, journal = {Cirugia y cirujanos}, volume = {85 Suppl 1}, number = {}, pages = {6-12}, doi = {10.1016/j.circir.2016.11.017}, pmid = {28126184}, issn = {2444-054X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anxiety/etiology/*therapy ; Celiac Disease/complications ; Colon/microbiology ; Comorbidity ; Contraindications, Drug ; Diarrhea/etiology/psychology/*therapy ; Diverticulosis, Colonic/complications ; Dysentery, Amebic/drug therapy/therapy ; Esophagitis/complications ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Hernia, Hiatal/complications ; Humans ; Irritable Bowel Syndrome/complications ; Jejunum/microbiology ; Malabsorption Syndromes/complications ; Male ; Metronidazole ; Pilot Projects ; Quinolines/therapeutic use ; }, abstract = {In the fourth century, during the Chinese Dong Jin dynasty, the doctor Ge Hong described good results after the oral administration of a suspension prepared from human faeces in patients with severe diarrhoea or food poisoning. Faecal microbiota transplantation has been used for five years in order to treat different diseases in addition to the severe diarrhoea caused by Clostridium difficile[1]. This paper aims to confirm that intestinal microbiota transplantation succeeds in reducing the negative impact of diseases such as severe diarrhoea, irritable bowel syndrome, anxiety, allergies, metabolic syndrome and others and that it is not only indicated for severe diarrhoea caused by C. difficile. This preliminary study included six patients who underwent faecal microbiota transplantation, aged 83, 76, 66, 37 and 36 years (four men and two women). An improvement in symptoms of 70% was observed. The methodology and criteria to be followed with donors are described and the results are listed in three tables. The methodology followed for the microbiota transplant is the same as that reported by other researchers for the treatment of C. difficile diarrhoea and other diseases. The discussion addresses the issues raised in other parts of the world in handling different pathologic entities, as well as genetic advances. The conclusions show encouraging results.}, }
@article {pmid28125667, year = {2017}, author = {Chu, ND and Smith, MB and Perrotta, AR and Kassam, Z and Alm, EJ}, title = {Profiling Living Bacteria Informs Preparation of Fecal Microbiota Transplantations.}, journal = {PloS one}, volume = {12}, number = {1}, pages = {e0170922}, pmid = {28125667}, issn = {1932-6203}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Gastrointestinal Tract/microbiology ; Humans ; *Microbiota ; }, abstract = {Fecal microbiota transplantation is a compelling treatment for recurrent Clostridium difficile infections, with potential applications against other diseases associated with changes in gut microbiota. But variability in fecal bacterial communities-believed to be the therapeutic agent-can complicate or undermine treatment efficacy. To understand the effects of transplant preparation methods on living fecal microbial communities, we applied a DNA-sequencing method (PMA-seq) that uses propidium monoazide (PMA) to differentiate between living and dead fecal microbes, and we created an analysis pipeline to identify individual bacteria that change in abundance between samples. We found that oxygen exposure degraded fecal bacterial communities, whereas freeze-thaw cycles and lag time between donor defecation and transplant preparation had much smaller effects. Notably, the abundance of Faecalibacterium prausnitzii-an anti-inflammatory commensal bacterium whose absence is linked to inflammatory bowel disease-decreased with oxygen exposure. Our results indicate that some current practices for preparing microbiota transplant material adversely affect living fecal microbial content and highlight PMA-seq as a valuable tool to inform best practices and evaluate the suitability of clinical fecal material.}, }
@article {pmid28122648, year = {2017}, author = {Kang, DW and Adams, JB and Gregory, AC and Borody, T and Chittick, L and Fasano, A and Khoruts, A and Geis, E and Maldonado, J and McDonough-Means, S and Pollard, EL and Roux, S and Sadowsky, MJ and Lipson, KS and Sullivan, MB and Caporaso, JG and Krajmalnik-Brown, R}, title = {Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {10}, pmid = {28122648}, issn = {2049-2618}, support = {T32 AI112542/AI/NIAID NIH HHS/United States ; }, mesh = {Abdominal Pain/drug therapy ; Adolescent ; Anti-Bacterial Agents/therapeutic use ; Autism Spectrum Disorder/diagnosis/microbiology/*therapy ; Bacteriophages/genetics/growth &amp; development ; Bifidobacterium/growth &amp; development ; Child ; Constipation/drug therapy ; DNA, Viral ; Desulfovibrio/growth &amp; development ; Diarrhea/drug therapy/microbiology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Diseases/drug therapy/microbiology/*therapy ; *Gastrointestinal Microbiome/genetics ; Gastrointestinal Tract/microbiology/virology ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Male ; Prevotella/growth &amp; development ; Probiotics/*therapeutic use ; }, abstract = {BACKGROUND: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10[13] bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.<br><br>RESULTS: MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8&#xa0;weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8&#xa0;weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8&#xa0;weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8&#xa0;weeks).<br><br>CONCLUSIONS: This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8&#xa0;weeks after treatment ended, suggesting a long-term impact.<br><br>TRIAL REGISTRATION: This trial was registered on the ClinicalTrials.gov, with the registration number&#xa0; NCT02504554.}, }
@article {pmid28116471, year = {2017}, author = {Lübbert, C and Mutters, R}, title = {[Gastrointestinal infections].}, journal = {Der Internist}, volume = {58}, number = {2}, pages = {149-169}, pmid = {28116471}, issn = {1432-1289}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antiviral Agents/therapeutic use ; Bacterial Infections/diagnosis/*therapy ; Diagnosis, Differential ; Diarrhea/*diagnosis/*therapy ; Evidence-Based Medicine ; Gastrointestinal Diseases/*diagnosis/*therapy ; Humans ; Symptom Assessment/methods ; Treatment Outcome ; Virus Diseases/diagnosis/*therapy ; }, abstract = {Infectious diarrhea is one of the most common diseases. This article summarizes the current state of the diagnostics and treatment and includes the most important pathogens, i.e. Norovirus, Rotavirus, Campylobacter, Salmonella, Shigella and pathogenic Escherichia coli. Infections caused by toxin-producing strains of Clostridium difficile are described in more detail due to the increasing importance. Symptomatic therapy is still the most important component of treatment. Empirical antibiotic therapy is reserved for severely ill patients with a high stool frequency, fever, bloody diarrhea, underlying immune deficiency or significant comorbidities. Increasing bacterial resistance (in particular against fluoroquinolones) has to be considered. Motility inhibitors are not recommended for infections due to Shiga toxin-producing E. coli, C. difficile infections (CDI) and severe enterocolitis caused by other pathogens. The macrocyclic antibiotic fidaxomicin can reduce the recurrence rate of CDI. Fecal microbiota transplantation (FMT) currently provides a reserve treatment option for multiple recurrences of CDI and is subject to the Medicines Act (Arzneimittelgesetz, AMG) in Germany.}, }
@article {pmid28115993, year = {2017}, author = {von Klitzing, E and Ekmekciu, I and Bereswill, S and Heimesaat, MM}, title = {Acute ileitis facilitates infection with multidrug resistant Pseudomonas aeruginosa in human microbiota-associated mice.}, journal = {Gut pathogens}, volume = {9}, number = {}, pages = {4}, pmid = {28115993}, issn = {1757-4749}, abstract = {BACKGROUND: The rising incidence of multidrug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa has become a serious issue in prevention of its spread particularly among hospitalized patients. It is, however, unclear whether distinct conditions such as acute intestinal inflammation facilitate P. aeruginosa infection of vertebrate hosts.<br><br>METHODS AND RESULTS: To address this, we analysed P. aeruginosa infection in human microbiota-associated (hma) mice with acute ileitis induced by peroral Toxoplasma gondii challenge. When perorally infected with P. aeruginosa at day 3 post ileitis induction, hma mice displayed higher intestinal P. aeruginosa loads as compared to hma mice without ileitis. However, the overall intestinal microbiota composition was not disturbed by P. aeruginosa (except for lowered bifidobacterial populations), and the infection did not further enhance ileal immune cell responses. Pro-inflammatory cytokines including IFN-&#x3b3; and IL-12p70 were similarly increased in ileum and mesenteric lymph nodes of P. aeruginosa infected and uninfected hma mice with ileitis. The anti-inflammatory cytokine IL-10 increased multifold upon ileitis induction, but interestingly more distinctly in P. aeruginosa infected as compared to uninfected controls. Immune responses were not restricted to the intestines as indicated by elevated pro-inflammatory cytokine levels in liver and kidney upon ileitis induction. However, except for hepatic TNF-&#x3b1; levels, P. aeruginosa infection did not result in more distinct pro-inflammatory cytokine secretion in liver and kidney of hma mice with ileitis. Whereas viable intestinal bacteria were more frequently detected in systemic compartments such as spleen and cardiac blood of P. aeruginosa infected than uninfected mice at day 7 following ileitis induction, P. aeruginosa infection did not exacerbate systemic pro-inflammatory sequelae, but resulted in lower IL-10 serum levels.<br><br>CONCLUSION: Acute intestinal inflammation facilitates infection of the vertebrate host with MDR bacteria including P. aeruginosa and might also pose particularly hospitalized patients at risk for acquisition. Since acute T. gondii induced inflammation might mask immunopathology caused by P. aeruginosa, a subacute or chronic inflammation model might be better suited to investigate the potential role of P. aeruginosa infection in the aggravation of intestinal disease.}, }
@article {pmid28115022, year = {2017}, author = {Velmurugan, G and Ramprasath, T and Swaminathan, K and Mithieux, G and Rajendhran, J and Dhivakar, M and Parthasarathy, A and Babu, DD and Thumburaj, LJ and Freddy, AJ and Dinakaran, V and Puhari, SS and Rekha, B and Christy, YJ and Anusha, S and Divya, G and Suganya, K and Meganathan, B and Kalyanaraman, N and Vasudevan, V and Kamaraj, R and Karthik, M and Jeyakumar, B and Abhishek, A and Paul, E and Pushpanathan, M and Rajmohan, RK and Velayutham, K and Lyon, AR and Ramasamy, S}, title = {Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis.}, journal = {Genome biology}, volume = {18}, number = {1}, pages = {8}, pmid = {28115022}, issn = {1474-760X}, support = {FS/11/67/28954/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Acetic Acid/metabolism ; Animals ; Biomarkers ; Blood Glucose ; Diabetes Mellitus/etiology/metabolism ; Disease Models, Animal ; Feces/chemistry/enzymology ; *Gastrointestinal Microbiome ; *Gluconeogenesis/drug effects ; *Glucose Intolerance/drug therapy ; Glucose Tolerance Test ; Humans ; Hyperglycemia/blood/etiology/metabolism ; Insecticides/*metabolism/toxicity ; Mice ; Organophosphates/*metabolism/toxicity ; Oxidative Stress ; }, abstract = {BACKGROUND: Organophosphates are the most frequently and largely applied insecticide in the world due to their biodegradable nature. Gut microbes were shown to degrade organophosphates and cause intestinal dysfunction. The diabetogenic nature of organophosphates was recently reported but the underlying molecular mechanism is unclear. We aimed to understand the role of gut microbiota in organophosphate-induced hyperglycemia and to unravel the molecular mechanism behind this process.<br><br>RESULTS: Here we demonstrate a high prevalence of diabetes among people directly exposed to organophosphates in rural India (n&#x2009;=&#x2009;3080). Correlation and linear regression analysis reveal a strong association between plasma organophosphate residues and HbA1c but no association with acetylcholine esterase was noticed. Chronic treatment of mice with organophosphate for 180&#xa0;days confirms the induction of glucose intolerance with no significant change in acetylcholine esterase. Further fecal transplantation and culture transplantation experiments confirm the involvement of gut microbiota in organophosphate-induced glucose intolerance. Intestinal metatranscriptomic and host metabolomic analyses reveal that gut microbial organophosphate degradation produces short chain fatty acids like acetic acid, which induces gluconeogenesis and thereby accounts for glucose intolerance. Plasma organophosphate residues are positively correlated with fecal esterase activity and acetate level of human diabetes.<br><br>CONCLUSION: Collectively, our results implicate gluconeogenesis as the key mechanism behind organophosphate-induced hyperglycemia, mediated by the organophosphate-degrading potential of gut microbiota. This study reveals the gut microbiome-mediated diabetogenic nature of organophosphates and hence that the usage of these insecticides should be reconsidered.}, }
@article {pmid28113162, year = {2016}, author = {Mertz, L}, title = {Omics Tech, Gut-on-a-Chip, and Bacterial Engineering: New Approaches for Treating Inflammatory Bowel Diseases.}, journal = {IEEE pulse}, volume = {7}, number = {5}, pages = {9-12}, doi = {10.1109/MPUL.2016.2592258}, pmid = {28113162}, issn = {2154-2317}, mesh = {Animals ; Biomedical Engineering/trends ; Biomedical Research/*trends ; Computational Biology/trends ; Gastrointestinal Microbiome/physiology ; Humans ; Inflammatory Bowel Diseases/*therapy ; Intestines/physiology ; Mice ; Microarray Analysis/*trends ; *Models, Biological ; }, abstract = {It was six years ago that fecal transplantation first received prominent media attention and the public began to fully appreciate that the bacteria and other microbes in their bodies could have a real impact on health.}, }
@article {pmid28109835, year = {2017}, author = {Vaiserman, AM and Koliada, AK and Marotta, F}, title = {Gut microbiota: A player in aging and a target for anti-aging intervention.}, journal = {Ageing research reviews}, volume = {35}, number = {}, pages = {36-45}, doi = {10.1016/j.arr.2017.01.001}, pmid = {28109835}, issn = {1872-9649}, mesh = {Aging/*immunology ; Diet Therapy/*methods ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; *Inflammation/immunology/physiopathology/therapy ; Multiple Chronic Conditions/*therapy ; }, abstract = {Aging-associated alterations in composition, diversity and functional features of intestinal microbiota are well-described in the modern literature. They are suggested to be caused by an age-related decline in immune system functioning (immunosenescence) and a low-grade chronic inflammation (inflammaging), which accompany many aging-associated pathologies. The microbiota-targeted dietary and probiotic interventions have been shown to favorably affect the host health and aging by an enhancement of antioxidant activity, improving immune homeostasis, suppression of chronic inflammation, regulation of fat deposition and metabolism and prevention of insulin resistance. Recently, a high effectiveness and safety of novel therapeutic application such as fecal microbiota transplantation in the prevention and treatment of age-related pathological conditions including atherosclerosis, type 2 diabetes and Parkinson's disease has been demonstrated. In this review, recent research findings are summarized on the role of gut micribiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in anti-aging medicine.}, }
@article {pmid28105618, year = {2017}, author = {Li, N and Tian, H and Ma, C and Ding, C and Ge, X and Gu, L and Zhang, X and Yang, B and Hua, Y and Zhu, Y and Zhou, Y}, title = {[Efficacy analysis of fecal microbiota transplantation in the treatment of 406 cases with gastrointestinal disorders].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {20}, number = {1}, pages = {40-46}, pmid = {28105618}, issn = {1671-0274}, mesh = {Adult ; Clostridioides difficile/*drug effects ; Clostridium Infections/*drug therapy ; Colitis, Ulcerative/*drug therapy ; Colonoscopy/adverse effects/methods ; Constipation/*drug therapy ; Crohn Disease/*drug therapy ; Diarrhea/chemically induced ; Fecal Microbiota Transplantation/*methods/*statistics &amp; numerical data ; Female ; Flatulence/chemically induced ; Gastrointestinal Diseases/*drug therapy ; Gastroscopy/methods ; Humans ; Intubation, Gastrointestinal/adverse effects/methods ; Irritable Bowel Syndrome/*drug therapy ; Male ; Middle Aged ; Nausea/chemically induced ; Retrospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for gastrointestinal disorders.<br><br>METHODS: Retrospective analysis of the clinical data of 406 patients who underwent FMT from May 2014 to April 2016 in the Intestinal Microenvironment Treatment Centre of Nanjing General Hospital was performed, including patients with constipation(276 cases), recurrent Clostridium Difficile infection (RCDI, 61 cases), ulcerative colitis(44 cases), irritable bowel syndrome (15 cases) and Crohn's disease(10 cases). Donors were completely unrelated, 18- to 50-year-old non-pregnant healthy adult, with healthy lifestyle and habits, without taking antibiotics, probiotics and other probiotics history within 3 months. There were three routes of FMT administration: patients received 6 days of frozen FMT by nasointestinal tube placed in the proximal jejunum under gastroscope (319 cases); patients received capsules FMT per day for 6 consecutive days (46 cases) or once 600 ml of treated fecal liquid infusion into colon and terminal ileum by colonoscopy(41 cases).<br><br>RESULTS: Clinical cure rate and improvement rate of different diseases receiving FMT were respectively as follows: RCDI was 85.2% (52/61) and 95.1%(58/61); constipation was 40.2%(111/276) and 67.4%(186/276); ulcerative colitis was 34.1%(15/44) and 68.2% (30/44); irritable bowel syndrome was 46.7% (7/15) and 73.3% (11/15) and Crohn disease was 30.0%(3/10) and 60.0%(6/10). RCDI had the best efficacy among these diseases(P<0.01). There was no significant difference between the three routes of FMT administration(P=0.829). The clinical cure rate and improvement rate of different routes were 43.3%(138/319) and 58.6% (187/319) respectively in nasogastric transplantation group, 41.5%(17/41) and 61.0%(25/41) in colonoscopy group, 37.0%(17/46) and 63.0% (29/46) in the capsule transplantation group. There was no serious adverse event during the follow-up. The most common side effects were respiratory discomfort (27.3%, 87/319) and increased venting (51.7%, 165/319) in nasogastric transplantation group. Diarrhea was the most common complication in colonoscopy group (36.6%, 15/41). The main symptoms were increased venting (50.0%, 23/46) and nausea(34.8%, 16/46) in oral capsule group. Side effect symptoms disappeared after the withdraw of nasogastric tube, or at the end of treatment, or during hospitalization for 1-3 days.<br><br>CONCLUSIONS: FMT is effective for many gastrointestinal disorders. No significant adverse event is found, while the associated mechanism should be further explored.}, }
@article {pmid28103289, year = {2017}, author = {Baro, E and Galperine, T and Denies, F and Lannoy, D and Lenne, X and Odou, P and Guery, B and Dervaux, B}, title = {Cost-Effectiveness Analysis of Five Competing Strategies for the Management of Multiple Recurrent Community-Onset Clostridium difficile Infection in France.}, journal = {PloS one}, volume = {12}, number = {1}, pages = {e0170258}, pmid = {28103289}, issn = {1932-6203}, mesh = {Aminoglycosides/economics/therapeutic use ; Anti-Bacterial Agents/economics/therapeutic use ; *Clostridioides difficile ; Community-Acquired Infections/*economics/*therapy ; Computer Simulation ; Cost-Benefit Analysis ; Decision Trees ; Enterocolitis, Pseudomembranous/*economics/*therapy ; Fecal Microbiota Transplantation/economics/methods ; Fidaxomicin ; France ; Health Care Costs ; Humans ; Models, Economic ; Quality-Adjusted Life Years ; Recurrence ; Vancomycin/economics/therapeutic use ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is characterized by high rates of recurrence, resulting in substantial health care costs. The aim of this study was to analyze the cost-effectiveness of treatments for the management of second recurrence of community-onset CDI in France.<br><br>METHODS: We developed a decision-analytic simulation model to compare 5 treatments for the management of second recurrence of community-onset CDI: pulsed-tapered vancomycin, fidaxomicin, fecal microbiota transplantation (FMT) via colonoscopy, FMT via duodenal infusion, and FMT via enema. The model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) among the 5 treatments. ICERs were interpreted using a willingness-to-pay threshold of &#x20ac;32,000/QALY. Uncertainty was evaluated through deterministic and probabilistic sensitivity analyses.<br><br>RESULTS: Three strategies were on the efficiency frontier: pulsed-tapered vancomycin, FMT via enema, and FMT via colonoscopy, in order of increasing effectiveness. FMT via duodenal infusion and fidaxomicin were dominated (i.e. less effective and costlier) by FMT via colonoscopy and FMT via enema. FMT via enema compared with pulsed-tapered vancomycin had an ICER of &#x20ac;18,092/QALY. The ICER for FMT via colonoscopy versus FMT via enema was &#x20ac;73,653/QALY. Probabilistic sensitivity analysis with 10,000 Monte Carlo simulations showed that FMT via enema was the most cost-effective strategy in 58% of simulations and FMT via colonoscopy was favored in 19% at a willingness-to-pay threshold of &#x20ac;32,000/QALY.<br><br>CONCLUSIONS: FMT via enema is the most cost-effective initial strategy for the management of second recurrence of community-onset CDI at a willingness-to-pay threshold of &#x20ac;32,000/QALY.}, }
@article {pmid28103145, year = {2017}, author = {Fischer, M and Bittar, M and Papa, E and Kassam, Z and Smith, M}, title = {Can you cause inflammatory bowel disease with fecal transplantation? A 31-patient case-series of fecal transplantation using stool from a donor who later developed Crohn's disease.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {205-207}, pmid = {28103145}, issn = {1949-0984}, mesh = {Adult ; Aged ; Bacteria/*classification/genetics ; Clostridium Infections/*therapy ; Crohn Disease/*etiology/pathology ; Donor Selection/standards ; Fecal Microbiota Transplantation/*adverse effects ; Feces/microbiology ; Female ; Follow-Up Studies ; Humans ; Inflammatory Bowel Diseases/*etiology/pathology ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; *Tissue Donors ; Treatment Outcome ; }, }
@article {pmid28102756, year = {2017}, author = {Newman, KM and Rank, KM and Vaughn, BP and Khoruts, A}, title = {Treatment of recurrent Clostridium difficile infection using fecal microbiota transplantation in patients with inflammatory bowel disease.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {303-309}, pmid = {28102756}, issn = {1949-0984}, support = {L30 DK099831/DK/NIDDK NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Clostridium Infections/*therapy ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*therapy ; Intestines/microbiology ; Male ; Middle Aged ; Recurrence ; Young Adult ; }, abstract = {We recently compared results of fecal microbiota transplantation (FMT) in patients with refractory, recurrent Clostridium difficile infection (rCDI), with and without underlying inflammatory bowel disease (IBD). Here we extend this cohort and analyze outcomes in greater detail by subtype of IBD. We find that FMT is generally effective in breaking the cycle of CDI recurrence, but its effects on overall IBD progression are much less predictable. We discuss several challenges intrinsic to this complex clinical situation and outline the next steps that can address these challenges going forward.}, }
@article {pmid28095292, year = {2016}, author = {Šarmírová, S and Nagyová, V and Štípalová, D and Drastichová, I and Šimonyiová, D and Sirotná, Z and Kissová, R and Pastuchová, K and Tirpáková, J and Kuba, D and Klement, C and Bopegamage, S}, title = {Should Enteroviruses Be Monitored in Natural Recreational Waters?.}, journal = {Central European journal of public health}, volume = {24}, number = {4}, pages = {333-336}, doi = {10.21101/cejph.a4368}, pmid = {28095292}, issn = {1210-7778}, mesh = {Enterovirus/*isolation &amp; purification ; *Environmental Monitoring ; Feces/virology ; Fresh Water/*virology ; Humans ; Polymerase Chain Reaction ; *Recreation ; Slovakia ; *Water Microbiology ; }, abstract = {Enteroviruses (EVs) infections occur worldwide. Although, infections by these viruses are often asymptomatic and go unnoticed, they can be shed in stool for several weeks. The EVs are associated with sporadic outbreaks and a wide range of clinical symptoms, occasionally accompanied with fatal consequences. Presently in the Slovak Republic (SR) recreational waters are tested only for bacterial indicators. Our aim was to monitor EVs in recreational waters. Water samples were collected during the years 2012-2014 from different recreational natural lakes in Central and West regions of SR. The samples were concentrated by centrifugation using the two-phase separation method recommended by the World Health Organization (WHO) used for EVs surveillance in the treated sewage waste water. Each of the two phases collected from the samples was analysed by polymerase chain reaction for detection of EVs and primary sequencing was done. Our study demonstrated presence of EVs in three localities consecutively for three years, indicating a probability of constant local source of faecal contamination. This is the first monitoring report on the occurrence of EVs in the natural recreational waters in SR.}, }
@article {pmid28093134, year = {2017}, author = {Khanna, S and Shin, A and Kelly, CP}, title = {Management of Clostridium difficile Infection in Inflammatory Bowel Disease: Expert Review from the Clinical Practice Updates Committee of the AGA Institute.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {15}, number = {2}, pages = {166-174}, doi = {10.1016/j.cgh.2016.10.024}, pmid = {28093134}, issn = {1542-7714}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/complications/*diagnosis/*drug therapy ; Humans ; Inflammatory Bowel Diseases/*complications ; }, abstract = {The purpose of this expert review is to synthesize the existing evidence on the management of Clostridium difficile infection in patients with underlying inflammatory bowel disease. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence. Best Practice Advice 1: Clinicians should test patients who present with a flare of underlying inflammatory bowel disease for Clostridium difficile infection. Best Practice Advice 2: Clinicians should screen for recurrent C difficile infection if diarrhea or other symptoms of colitis persist or return after antibiotic treatment for C difficile infection. Best Practice Advice 3: Clinicians should consider treating C difficile infection in inflammatory bowel disease patients with vancomycin instead of metronidazole. Best Practice Advice 4: Clinicians strongly should consider hospitalization for close monitoring and aggressive management for inflammatory bowel disease patients with C difficile infection who have profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other evidence of sepsis. Best Practice Advice 5: Clinicians may postpone escalation of steroids and other immunosuppression agents during acute C difficile infection until therapy for C difficile infection has been initiated. However, the decision to withhold or continue immunosuppression in inflammatory bowel disease patients with C difficile infection should be individualized because there is insufficient existing robust literature on which to develop firm recommendations. Best Practice Advice 6: Clinicians should offer a referral for fecal microbiota transplantation to inflammatory bowel disease patients with recurrent C difficile infection.}, }
@article {pmid28092309, year = {2017}, author = {Haak, BW and Levi, M and Wiersinga, WJ}, title = {Microbiota-targeted therapies on the intensive care unit.}, journal = {Current opinion in critical care}, volume = {23}, number = {2}, pages = {167-174}, doi = {10.1097/MCC.0000000000000389}, pmid = {28092309}, issn = {1531-7072}, mesh = {Dysbiosis ; Humans ; *Intensive Care Units ; *Microbiota ; Pneumonia, Ventilator-Associated/microbiology/*therapy ; Probiotics/*therapeutic use ; }, abstract = {PURPOSE OF REVIEW: The composition and diversity of the microbiota of the human gut, skin, and several other sites is severely deranged in critically ill patients on the ICU, and it is likely that these disruptions can negatively affect outcome. We here review new and ongoing studies that investigate the use of microbiota-targeted therapeutics in the ICU, and provide recommendations for future research.<br><br>RECENT FINDINGS: Practically every intervention in the ICU as well as the physiological effects of critical illness itself can have a profound impact on the gut microbiota. Therapeutic modulation of the microbiota, aimed at restoring the balance between 'pathogenic' and 'health-promoting' microbes is therefore of significant interest. Probiotics have shown to be effective in the treatment of ventilator-associated pneumonia, and the first fecal microbiota transplantations have recently been safely and successfully performed in the ICU. However, all-encompassing data in this vulnerable patient group remain sparse, and only a handful of novel studies that study microbiota-targeted therapies in the ICU are currently ongoing.<br><br>SUMMARY: Enormous strides have been made in characterizing the gut microbiome of critically ill patients in the ICU, and an increasing amount of preclinical data reveals the huge potential of microbiota-targeted therapies. Further understanding of the causes and consequences of dysbiosis on ICU-related outcomes are warranted to push the field forward.}, }
@article {pmid28090385, year = {2016}, author = {Moelling, K and Broecker, F}, title = {Fecal microbiota transplantation to fight Clostridium difficile infections and other intestinal diseases.}, journal = {Bacteriophage}, volume = {6}, number = {4}, pages = {e1251380}, pmid = {28090385}, issn = {2159-7073}, abstract = {We have analyzed fecal bacterial and viral communities of a patient with recurrent C. difficile infection (rCDI) who was cured by fecal microbiota transplantation (FMT). The "Zürich Patient" experienced immediate cure and has remained free of symptoms for now over 5 y. Donor-similar bacterial compositions after 4.5 y post-FMT demonstrated sustainable engraftment of donor microbiota predominated by Bacteroidetes and Firmicutes bacteria. Appearance of beneficial species Faecalibacterium prausnitzii and Akkermansia municiphila was detected while disease-related Proteobacteria decreased. Stabilization of the microbiota took longer than expected from the rapidly improving clinical symptoms, suggesting the need for longer-lasting patient observation. The virome was mainly composed of Caudovirales bacteriophages but surprisingly also contained sequences related to a Chlorella giant virus that normally infects green algae not known to inhabitate the human intestine. FMT is highly effective against rCDI and is presently broadening its application to other conditions including inflammatory bowel disease (IBD). Here, we discuss the prospects and challenges of FMT against rCDI and other indications including a focus on bacteriophages.}, }
@article {pmid28087657, year = {2017}, author = {Cammarota, G and Ianiro, G and Tilg, H and Rajilić-Stojanović, M and Kump, P and Satokari, R and Sokol, H and Arkkila, P and Pintus, C and Hart, A and Segal, J and Aloi, M and Masucci, L and Molinaro, A and Scaldaferri, F and Gasbarrini, G and Lopez-Sanroman, A and Link, A and de Groot, P and de Vos, WM and Högenauer, C and Malfertheiner, P and Mattila, E and Milosavljević, T and Nieuwdorp, M and Sanguinetti, M and Simren, M and Gasbarrini, A and , }, title = {European consensus conference on faecal microbiota transplantation in clinical practice.}, journal = {Gut}, volume = {66}, number = {4}, pages = {569-580}, pmid = {28087657}, issn = {1468-3288}, mesh = {*Clostridioides difficile ; Donor Selection ; Enterocolitis, Pseudomembranous/*therapy ; Europe ; Evidence-Based Medicine ; *Fecal Microbiota Transplantation/adverse effects/methods/standards ; Health Facilities ; Hospital Units/organization &amp; administration ; Humans ; *Patient Selection ; Specimen Handling/*methods ; }, abstract = {Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.}, }
@article {pmid28084496, year = {2017}, author = {de Groot, N and Stanbury, K and de Vos-Rouweler, AJ and de Groot, NG and Poirier, N and Blancho, G and de Luna, C and Doxiadis, GG and Bontrop, RE}, title = {A quick and robust MHC typing method for free-ranging and captive primate species.}, journal = {Immunogenetics}, volume = {69}, number = {4}, pages = {231-240}, pmid = {28084496}, issn = {1432-1211}, support = {HHSN272201100013C/AI/NIAID NIH HHS/United States ; HHSN272201100013I/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; DNA Copy Number Variations/*genetics ; Female ; Genotype ; Humans ; Major Histocompatibility Complex/*genetics ; Male ; Microsatellite Repeats/*genetics ; Phylogeny ; Polymorphism, Genetic/*genetics ; Primates/*classification/*genetics ; }, abstract = {Gene products of the major histocompatibility complex (MHC) of human and non-human primates play a crucial role in adaptive immunity, and most of the relevant genes not only show a high degree of variability (polymorphism) but also copy number variation (CNV) is observed. Due to this diversity, MHC proteins influence the capability of individuals to cope with various pathogens. MHC and/or MHC-linked gene products such as odorant receptor genes are thought to influence mate choice and reproductive success. Therefore, MHC typing of wild and captive primate populations is considered to be useful in conservation biology, which is, however, often hampered by the need of invasive and time-consuming methods. All intact Mhc-DRB genes in primates appear to possess a complex and highly divergent microsatellite, DRB-STR. A panel of 154 pedigreed olive baboons (Papio anubis) was examined for their DRB content by DRB-STR analysis of genomic DNA. Using the same methodology on DNA of feces samples, DRB variability of a silvery gibbon population (Hylobates moloch) (N = 24), an endangered species, could successfully be studied. In both species, length determination of the DRB-STR resulted in the definition of unique genotyping patterns that appeared to be specific for a certain chromosome. Moreover, the different STR lengths were shown to segregate with the allelic variation of the respective gene. The results obtained expand data gained previously on DRB-STR typing in macaques, great apes, and humans and strengthen the conclusion that this protocol is applicable in molecular ecology, conservation biology, and colony management, especially of endangered primate species.}, }
@article {pmid28083955, year = {2017}, author = {Bhat, V and Vira, H and Khattry, N and Toshniwal, M}, title = {Cryptococcus laurentii diarrhea post hematopoietic stem cell transplant.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {19}, number = {2}, pages = {}, doi = {10.1111/tid.12663}, pmid = {28083955}, issn = {1399-3062}, mesh = {Administration, Intravenous ; Administration, Oral ; Adult ; Antibiotic Prophylaxis ; Antifungal Agents/administration &amp; dosage/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; C-Reactive Protein/analysis ; Carmustine/adverse effects/therapeutic use ; Cryptococcosis/blood/drug therapy/*microbiology ; Cryptococcus/*isolation &amp; purification ; Cytarabine/adverse effects/therapeutic use ; Diarrhea/blood/drug therapy/*microbiology ; Etoposide/adverse effects/therapeutic use ; Feces/microbiology ; Fluconazole/therapeutic use ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Hodgkin Disease/*surgery ; Humans ; Melphalan/adverse effects/therapeutic use ; Microbial Sensitivity Tests ; Transplantation Conditioning/adverse effects/methods ; Transplantation, Autologous/adverse effects ; Voriconazole/administration &amp; dosage/*therapeutic use ; }, abstract = {We report the recent isolation of Cryptococcus laurentii from the feces of a patient with Hodgkin's lymphoma who underwent autologous hematopoietic stem cell transplant (HSCT). The organism was identified using microscopic morphology, cultural characteristics, and biochemical tests including sugar assimilation. Minimum inhibitory concentration of various antifungals was determined by microbroth dilution method. The recovery of pure culture of C. laurentii from stool culture, and the patient's response to treatment with voriconazole support its potential etiological role. To the best of our knowledge, we report the first case of diarrhea caused by C. laurentii in an HSCT recipient.}, }
@article {pmid28077694, year = {2017}, author = {Woodworth, MH and Neish, EM and Miller, NS and Dhere, T and Burd, EM and Carpentieri, C and Sitchenko, KL and Kraft, CS}, title = {Laboratory Testing of Donors and Stool Samples for Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection.}, journal = {Journal of clinical microbiology}, volume = {55}, number = {4}, pages = {1002-1010}, pmid = {28077694}, issn = {1098-660X}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; }, mesh = {Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods/*standards ; Feces/*microbiology ; Humans ; Mass Screening/*methods ; Secondary Prevention/*methods ; *Tissue Donors ; United States ; United States Food and Drug Administration ; }, abstract = {Fecal microbiota transplantation is an efficacious and inexpensive therapy for recurrent Clostridium difficile infection, yet its safety is thought to depend on appropriate fecal donor screening. FDA guidance for regulation of this procedure is in flux, but screening and manufacture of fecal material from asymptomatic donors present many challenges to clinical laboratories. This minireview summarizes FDA regulatory changes, principles of donor selection, and recommended laboratory screening practices for fecal microbiota transplantation.}, }
@article {pmid28077203, year = {2017}, author = {Marshall, LL and Peasah, S and Stevens, GA}, title = {Clostridium difficile Infection in Older Adults: Systematic Review of Efforts to Reduce Occurrence and Improve Outcomes.}, journal = {The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists}, volume = {32}, number = {1}, pages = {24-41}, doi = {10.4140/TCP.n.2017.24}, pmid = {28077203}, issn = {0888-5109}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/administration &amp; dosage/adverse effects/*therapeutic use ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*epidemiology/*prevention &amp; control ; Homes for the Aged/organization &amp; administration ; Humans ; Infection Control/*organization &amp; administration ; Inservice Training ; Nursing Homes/organization &amp; administration ; Outcome and Process Assessment, Health Care ; Policy ; Practice Guidelines as Topic ; Recurrence ; Risk Factors ; }, abstract = {OBJECTIVE: Provide a systematic review of the primary literature on efforts to reduce Clostridium difficile infection (CDI) occurrence and improve outcomes in older adults.<br><br>PubMed and CINAHL databases were searched for research studies using search terms CDI, CDI prevention, reduction, control, management, geriatric, elderly, adults 65 years of age and older. The MeSH categories Aged and Aged, 80 and older, were used. A second search of PubMed, CINAHL, National Guideline Clearinghouse, and TRIP databases was conducted for primary, secondary, and tertiary literature for CDI epidemiology, burden, and management in adults of all ages, and prevention and management guidelines. Of the 2,263 articles located, 105 were selected for full review: 55 primary and 50 secondary, tertiary. Primary literature selected for full review included studies of interventions to prevent, reduce occurrence, control, manage, or improve outcomes in adults 65 years of age and older. Patient settings included the community, assisted living, nursing facility, subacute care, or hospital.<br><br>DATA SYNTHESIS: The main outcome measures for research studies were whether the studied intervention prevented, reduced occurrence, controlled, managed, or improved outcomes. Studies were conducted in acute or long-term hospitals, with a few in nursing facilities. Interventions that prevented or reduced CDI included antibiotic policy changes, education, procedure changes, infection control, and multi-intervention approaches. There were few management studies for adults 65 years of age and older or for all adults with results stratified by age. Treatments studied included efficacy of fidaxomicin, metronidazole, vancomycin, and fecal microbiota transplant. Though clinical outcomes were slightly less robust in those 65 years of age and older, age was not an independent predictor of success or failure. The current prevention and management guidelines for adults of all ages, as well as special considerations in skilled nursing facilities, extracted from the secondary/tertiary literature selected, are summarized.<br><br>CONCLUSION: There are a limited number of studies designed for older adults. Our findings suggest that guideline recommendations for adults are adequate and appropriate for older adults. Exposure to antibiotics and Clostridium difficile remain the two major risk factors for CDI, reinforcing the importance of antibiotic stewardship and infection control.}, }
@article {pmid28074537, year = {2017}, author = {Castellani, C and Singer, G and Kaiser, M and Kaiser, T and Huang, J and Sperl, D and Kashofer, K and Fauler, G and Guertl-Lackner, B and Höfler, G and Till, H}, title = {Neuroblastoma causes alterations of the intestinal microbiome, gut hormones, inflammatory cytokines, and bile acid composition.}, journal = {Pediatric blood &amp; cancer}, volume = {64}, number = {8}, pages = {}, doi = {10.1002/pbc.26425}, pmid = {28074537}, issn = {1545-5017}, mesh = {Animals ; Bile Acids and Salts/*metabolism ; Cell Line, Tumor ; Chromatography, High Pressure Liquid ; Cytokines/*metabolism ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Heterografts ; Humans ; Inflammation/pathology ; Male ; Mass Spectrometry ; Mice ; Mice, Nude ; Neuroblastoma/*pathology ; }, abstract = {OBJECTIVE: To assess the effect of neuroblastoma (NB) on the intestinal microbiome, metabolism, and inflammatory parameters in a murine model.<br><br>MATERIALS AND METHODS: Athymic Hsd:Fox1nu mice received subperitoneal implantation of human NB cells (MHH-NB11) (tumor group, TG) or culture medium (sham group). Following 10 weeks of tumor growth, all animals were sacrificed to collect total white adipose tissue (WAT). Luminex assays were performed for gut hormone and inflammation marker analysis. Bile acids were measured by high-performance liquid chromatography-mass spectrometry in feces and serum. The microbiome of the ileal content was determined by 16S rDNA next-generation sequencing.<br><br>RESULTS: At 10 weeks, tumors masses in the TG reached a mean weight of 1.10 g (interquartile range 3.45 g) associated with a significant reduction in WAT. Furthermore, in the TG, there was a marked reduction in leptin and an increase in glucagon-like peptide 1 serum levels. Moreover, the TG mice displayed a pro-inflammatory profile, with significant increases in monocyte chemotactic protein 1, tumor necrosis factor alpha, and interleukin-10. Lithocholic acid, deoxycholic acid, and ursodeoxycholic acid were significantly decreased in the stool of TG mice. Significant alterations of the intestinal microbiome were found in the ileal contents of the TG.<br><br>CONCLUSIONS: The present study provides a first glimpse that human NB in a murine model induces tumor cachexia associated with alterations in metabolic and inflammatory parameters, as well as changes in the intestinal microbiota. Since the intestinal microbiome is known to contribute to the host's ability to harvest energy, a favorable modulation of the intestinal microbiome in tumor patients could potentially represent a novel therapeutic target to prevent tumor-associated cachexia.}, }
@article {pmid28074093, year = {2016}, author = {Gong, D and Gong, X and Wang, L and Yu, X and Dong, Q}, title = {Involvement of Reduced Microbial Diversity in Inflammatory Bowel Disease.}, journal = {Gastroenterology research and practice}, volume = {2016}, number = {}, pages = {6951091}, pmid = {28074093}, issn = {1687-6121}, abstract = {A considerable number of studies have been conducted to study the microbial profiles in inflammatory conditions. A common phenomenon in inflammatory bowel disease (IBD) is the reduction of the diversity of microbiota, which demonstrates that microbial diversity negatively correlates with disease severity in IBD. Increased microbial diversity is known to occur in disease remission. Species diversity plays an important role in maintaining the stability of the intestinal ecosystem as well as normal ecological function. A reduction in microbial diversity corresponds to a decrease in the stability of the ecosystem and can impair ecological function. Fecal microbiota transplantation (FMT), probiotics, and prebiotics, which aim to modulate the microbiota and restore its normal diversity, have been shown to be clinically efficacious. In this study, we hypothesized that a reduction in microbial diversity could play a role in the development of IBD.}, }
@article {pmid28068341, year = {2017}, author = {Kazerouni, A and Wein, LM}, title = {Exploring the Efficacy of Pooled Stools in Fecal Microbiota Transplantation for Microbiota-Associated Chronic Diseases.}, journal = {PloS one}, volume = {12}, number = {1}, pages = {e0163956}, pmid = {28068341}, issn = {1932-6203}, mesh = {Algorithms ; Chronic Disease ; *Fecal Microbiota Transplantation/methods ; Gastroenteritis/*microbiology/*therapy ; Humans ; *Microbiota ; *Models, Theoretical ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation is being assessed as a treatment for chronic microbiota-related diseases such as ulcerative colitis. Results from an initial randomized trial suggest that remission rates depend on unobservable features of the fecal donors and observable features of the patients. We use mathematical modeling to assess the efficacy of pooling stools from different donors during multiple rounds of treatment. In the model, there are two types of patients and two types of donors, where the patient type is observable and the donor type (effective or not effective) is not observable. In the model, clinical outcomes from earlier rounds of treatment are used to estimate the current likelihood that each donor is effective, and then each patient in each round is treated by a pool of donors that are currently deemed to be the most effective. Relative to the no-pooling case, pools of size two or three significantly increase the proportion of patients in remission during the first several rounds of treatment. Although based on data from a single randomized trial, our modeling suggests that pooling of stools - via daily cycling of encapsulated stool from several different donors - may be beneficial in fecal microbiota transplantation for chronic microbiota-related diseases.}, }
@article {pmid28067296, year = {2017}, author = {Xiao, X and Nakatsu, G and Jin, Y and Wong, S and Yu, J and Lau, JY}, title = {Gut Microbiota Mediates Protection Against Enteropathy Induced by Indomethacin.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {40317}, pmid = {28067296}, issn = {2045-2322}, mesh = {Animals ; Anti-Bacterial Agents ; *Gastrointestinal Microbiome/drug effects/genetics ; Indomethacin ; Intestinal Diseases/*chemically induced/*microbiology/prevention &amp; control ; Intestinal Mucosa/drug effects/microbiology/pathology ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Non-steroidal anti-inflammatory drugs (NSAIDs) can cause significant small bowel injuries. The role of gut microbiota in this NSAID-induced enteropathy is poorly understood. We studied the dynamic changes in gut microbiota following indomethacin administration in mice, and investigated the effects of these adaptive changes on subsequent NSAID-induced enteropathy. The changes in gut microbiota were studied using 16S rRNA sequencing, and the effects of such changes were investigated using antibiotics and a faecal transplantation model. After indomethacin treatment, significant adaptive changes in gut microbiota were observed, including increased abundance of Firmicutes and decreased abundance in that of Bacteroidetes. Depletion of gut microbiota with antibiotics led to a higher mortality (P = 0.0021) in mice compared to controls. Mice pre-transplanted with adaptively changed microbiota showed less small bowel injury and lower levels of pro-inflammatory cytokines when exposed to indomethacin. In summary, this study identifies adaptive changes in the gut microbiota upon indomethacin administration, which can in turn ameliorate further NSAID-induced injury. The heightened mortality with antibiotic depletion of the adaptively changed microbiota suggests its important role in protecting against such injury. This study provides insight for future efforts to target the microbiota as a therapeutic strategy.}, }
@article {pmid28066039, year = {2016}, author = {Edmond, MB}, title = {THE POWER OF POOP: FECAL MICROBIOTA TRANSPLANTATION FOR CLOSTRIDIUM DIFFICILE INFECTION.}, journal = {Transactions of the American Clinical and Climatological Association}, volume = {127}, number = {}, pages = {71-80}, pmid = {28066039}, issn = {0065-7778}, mesh = {Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; }, abstract = {The human gut is colonized with 200 to 1,000 bacterial species. Administration of antibiotics reduces the diversity of the intestinal microbiota, reduces colonization resistance, and can lead to infection with Clostridium difficile. These infections have become more prevalent and increasingly patients are experiencing multiple recurrences that are incurable with standard treatment. Although fecal microbiota transplantation (FMT) has been used for centuries in human and veterinary medicine, only recently has it be shown to be highly effective for recurrent C. difficile infection. The goal of FMT is to re-introduce a complete, stable community of gut microorganisms to repair or replace the disrupted native microbiota. FMT can be delivered via nasoenteric tube, colonoscopy, or enema. Despite a cure rate approximating 90%, many barriers to FMT have limited its availability to patients. The recent development of a not-for-profit stool bank has helped to make this therapy more accessible. Additional indications for FMT are currently under investigation.}, }
@article {pmid28059612, year = {2017}, author = {Laffin, M and Millan, B and Madsen, KL}, title = {Fecal microbial transplantation as a therapeutic option in patients colonized with antibiotic resistant organisms.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {221-224}, pmid = {28059612}, issn = {1949-0984}, support = {//CIHR/Canada ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/therapy ; *Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation/*trends ; Feces/microbiology ; Gastrointestinal Microbiome ; Hepatic Encephalopathy/therapy ; Humans ; Inflammatory Bowel Diseases/therapy ; Mental Disorders/therapy ; Metabolic Diseases/therapy ; Risk Factors ; }, abstract = {Despite increasing interest in fecal microbiota transplantation (FMT), its full therapeutic potential has yet to be determined. Since its increase in popularity, FMT has been shown to be highly effective in the treatment of both Clostridium difficile infection (CDI) and its recurrent form. Interest in FMT now expands well beyond the treatment of CDI to other processes with known associations to the microbiota such as antibiotic resistant infections, inflammatory bowel disease (IBD), hepatic encephalopathy, neuropsychiatric disorders, and metabolic disease. The rampant use and misuse of antibiotics in both medicine and agriculture has resulted in an increase in antibiotic resistant organisms which pose a significant risk to human health. The purpose of this commentary is to address the general issue of antibiotic resistance in the human microbiota and the restorative potential of FMT in this area.}, }
@article {pmid28058011, year = {2016}, author = {Wang, AY and Popov, J and Pai, N}, title = {Fecal microbial transplant for the treatment of pediatric inflammatory bowel disease.}, journal = {World journal of gastroenterology}, volume = {22}, number = {47}, pages = {10304-10315}, pmid = {28058011}, issn = {2219-2840}, mesh = {Adolescent ; Adult ; Age Factors ; Attitude of Health Personnel ; Child ; Child, Preschool ; Colitis, Ulcerative/diagnosis/microbiology/*surgery ; Crohn Disease/diagnosis/microbiology/*surgery ; *Fecal Microbiota Transplantation/adverse effects/history ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Health Knowledge, Attitudes, Practice ; History, 20th Century ; History, Ancient ; Humans ; Infant ; Patient Acceptance of Health Care ; Treatment Outcome ; Young Adult ; }, abstract = {The role of fecal microbial transplant (FMT) in the treatment of pediatric gastrointestinal disease has become increasingly popular among pediatric practitioners, patients, and parents. The success of FMT for the treatment of recurrent Clostridium difficile infection (RCDI) has bolstered interest in its potential application to other disease states, such as inflammatory bowel disease (IBD). FMT has particular interest in pediatrics, given the concerns of patients and parents about rates of adverse events with existing therapeutic options, and the greater cumulative medication burden associated with childhood-onset disease. Published literature on the use of FMT in pediatrics is sparse. Only 45 pediatric patients treated for RCDI have been reported, and only 27 pediatric patients with pediatric IBD. The pediatric microbiome may uniquely respond to microbial-based therapies. This review will provide a comprehensive overview of fecal microbial transplant and its potential role in the treatment of pediatric inflammatory bowel disease. We will discuss the microbiome in pediatric inflammatory bowel disease, existing adult and pediatric literature on the use of FMT in IBD treatment, and pediatric FMT trials that are currently recruiting patients. This review will also discuss features of the microbiome that may be associated with host response in fecal transplant, and potential challenges and opportunities for the future of FMT in pediatric IBD treatment.}, }
@article {pmid28057560, year = {2017}, author = {Ianiro, G and Valerio, L and Masucci, L and Pecere, S and Bibbò, S and Quaranta, G and Posteraro, B and Currò, D and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year, single-centre cohort study.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {23}, number = {5}, pages = {337.e1-337.e3}, doi = {10.1016/j.cmi.2016.12.025}, pmid = {28057560}, issn = {1469-0691}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile ; Clostridium Infections/*therapy ; Cohort Studies ; Colonoscopy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Treatment Failure ; }, abstract = {OBJECTIVES: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI). Although a single faecal infusion is usually sufficient to eradicate CDI, a considerable number of patients need multiple infusions to be cured. The aim of this study was to identify predictors of failure after single faecal infusion in patients with recurrent CDI.<br><br>METHODS: We included patients with recurrent CDI prospectively treated with FMT by colonoscopy. By means of univariate and multivariate analysis, variables including female gender, age, number of CDI recurrences, severity of CDI, hospitalization, inadequate bowel preparation, unrelated donor, and use of frozen faeces, were assessed to predict failure after single faecal infusion.<br><br>RESULTS: Sixty-four patients (39 women; mean age 74 years) were included. Of them, 44 (69%) were cured by a single faecal infusion, whereas 20 (31%) needed repeat infusions. Overall, FMT cured 62 of 64 (97%) patients. In the subgroup of patients with severe CDI, only eight of 26 (30%) were cured with a single infusion. At multivariate analysis, severe CDI (OR 24.66; 95% CI 4.44-242.08; p 0.001) and inadequate bowel preparation (OR 11.53; 95% CI 1.71-115.51; p 0.019) were found to be independent predictors of failure after single faecal infusion.<br><br>CONCLUSIONS: Severe CDI and inadequate bowel preparation appear to be independent predictors of failure after single faecal infusion in patients treated with FMT by colonoscopy for recurrent CDI. Our results may help to optimize protocols and outcomes of FMT in patients with recurrent CDI.}, }
@article {pmid28056490, year = {2017}, author = {Maroni, L and Hohenester, SD and van de Graaf, SFJ and Tolenaars, D and van Lienden, K and Verheij, J and Marzioni, M and Karlsen, TH and Oude Elferink, RPJ and Beuers, U}, title = {Knockout of the primary sclerosing cholangitis-risk gene Fut2 causes liver disease in mice.}, journal = {Hepatology (Baltimore, Md.)}, volume = {66}, number = {2}, pages = {542-554}, doi = {10.1002/hep.29029}, pmid = {28056490}, issn = {1527-3350}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Biopsy, Needle ; Cholangitis, Sclerosing/*genetics/*pathology ; Disease Models, Animal ; Disease Progression ; Fucosyltransferases/*genetics ; *Gene Expression Regulation ; Genome-Wide Association Study ; Humans ; Immunohistochemistry ; Liver Cirrhosis/genetics/*pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Portacaval Shunt, Surgical ; Portal System/*pathology ; Random Allocation ; Real-Time Polymerase Chain Reaction/methods ; Risk Assessment ; Galactoside 2-alpha-L-fucosyltransferase ; }, abstract = {UNLABELLED: The etiopathogenesis of primary sclerosing cholangitis is unknown. Genetic variants of fucosyltransferase 2 (FUT2) have been identified in genome-wide association studies as risk factors for primary sclerosing cholangitis. We investigated the role of Fut2 in murine liver pathophysiology by studying Fut2[-/-] mice. Fut2[-/-] mice were viable and fertile, had lower body weight than wild-type (wt) littermates and gray fur. Half of the Fut2[-/-] mice showed serum bile salt levels 40 times higher than wt (Fut2[-/-][high]), whereas the remainder were normocholanemic (Fut2[-/-][low]). Fut2[-/-] mice showed normal serum liver tests, bile flow, biliary bile salt secretion, fecal bile salt loss, and expression of major hepatocellular bile salt transporters and cytochrome P450 7a1, the key regulator of bile salt synthesis, indicating that elevated serum bile salts in Fut2[-/-][high] mice were not explained by cholestasis. Fut2[-/-][high] mice, but not Fut2[-/-][low] mice, were sensitive to hydrophobic bile salt feeding (0.3% glycochenodeoxycholate); they rapidly lost weight and showed elevation of serum liver tests (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase) and areas of liver parenchymal necrosis. Histomorphological evaluation revealed the presence of paraportal shunting vessels, increased numbers of portal vascular structures, wall thickening of some portal arteries, and periductal fibrosis in Fut2[-/-][high] mice more than Fut2[-/-][low] mice and not wt mice. Unconjugated bilirubin and ammonia were or tended to be elevated in Fut2[-/-][high] mice only. Portosystemic shunting was demonstrated by portal angiography, which disclosed virtually complete portosystemic shunting in Fut2[-/-][high] mice, discrete portosystemic shunting in Fut2[-/-][low] mice, and no shunting in wt littermates.<br><br>CONCLUSION: Liver pathology in Fut2[-/-] mice is dominated by consequences of portosystemic shunting resulting in microcirculatory disturbances, mild (secondary) periductal fibrosis, and sensitivity toward human bile salt toxicity. (Hepatology 2017;66:542-554).}, }
@article {pmid28052560, year = {2017}, author = {van der Lelie, D and Taghavi, S and Henry, C and Gilbert, JA}, title = {The microbiome as a source of new enterprises and job creation: Considering clinical faecal and synthetic microbiome transplants and therapeutic regulation.}, journal = {Microbial biotechnology}, volume = {10}, number = {1}, pages = {4-5}, pmid = {28052560}, issn = {1751-7915}, mesh = {Fecal Microbiota Transplantation/*methods/*standards ; *Gastrointestinal Microbiome ; *Health Policy ; Humans ; *Microbiota ; Transplants/*standards ; }, }
@article {pmid28051919, year = {2017}, author = {Sadowsky, MJ and Staley, C and Heiner, C and Hall, R and Kelly, CR and Brandt, L and Khoruts, A}, title = {Analysis of gut microbiota - An ever changing landscape.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {268-275}, pmid = {28051919}, issn = {1949-0984}, mesh = {Animals ; Clostridium Infections/therapy ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {In the last two decades, the field of metagenomics has greatly expanded due to improvement in sequencing technologies allowing for a more comprehensive characterization of microbial communities. The use of these technologies has led to an unprecedented understanding of human, animal, and environmental microbiomes and have shown that the gut microbiota are comparable to an organ that is intrinsically linked with a variety of diseases. Characterization of microbial communities using next-generation sequencing-by-synthesis approaches have revealed important shifts in microbiota associated with debilitating diseases such as Clostridium difficile infection. But due to limitations in sequence read length, primer biases, and the quality of databases, genus- and species-level classification have been difficult. Third-generation technologies, such as Pacific Biosciences' single molecule, real-time (SMRT) approach, allow for unbiased, more specific identification of species that are likely clinically relevant. Comparison of Illumina next-generation characterization and SMRT sequencing of samples from patients treated for C. difficile infection revealed similarities in community composition at the phylum and family levels, but SMRT sequencing further allowed for species-level characterization - permitting a better understanding of the microbial ecology of this disease. Thus, as sequencing technologies continue to advance, new species-level insights can be gained in the study of complex and clinically-relevant microbial communities.}, }
@article {pmid28050036, year = {2017}, author = {Chang, BW and Rezaie, A}, title = {Irritable Bowel Syndrome-Like Symptoms Following Fecal Microbiota Transplantation: A Possible Donor-Dependent Complication.}, journal = {The American journal of gastroenterology}, volume = {112}, number = {1}, pages = {186-187}, pmid = {28050036}, issn = {1572-0241}, mesh = {Adult ; Clostridium Infections/*therapy ; Donor Selection/methods ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; *Irritable Bowel Syndrome/etiology/physiopathology/prevention &amp; control/therapy ; Patient Care Management ; }, }
@article {pmid28049862, year = {2017}, author = {Lee, HJ and Choi, JK and Ryu, HS and Choi, CH and Kang, EH and Park, KS and Min, YW and Hong, KS}, title = {Therapeutic Modulation of Gut Microbiota in Functional Bowel Disorders.}, journal = {Journal of neurogastroenterology and motility}, volume = {23}, number = {1}, pages = {9-19}, pmid = {28049862}, issn = {2093-0879}, abstract = {Functional bowel disorders (FBDs) are functional gastrointestinal disorders with symptoms attributable to the middle or lower gastrointestinal tract. These include irritable bowel syndrome, functional bloating, functional constipation, functional diarrhea, and unspecified FBD. Increasing evidence has emerged of late that intestinal microbiota is involved in the pathogenesis of FBDs. In this review, the therapeutic benefits and future perspectives of the currently available strategies for modifying the gut microbiota in FBDs are described, focusing primarily on irritable bowel syndrome and functional constipation.}, }
@article {pmid28045919, year = {2017}, author = {Lindheim, L and Bashir, M and Münzker, J and Trummer, C and Zachhuber, V and Leber, B and Horvath, A and Pieber, TR and Gorkiewicz, G and Stadlbauer, V and Obermayer-Pietsch, B}, title = {Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study.}, journal = {PloS one}, volume = {12}, number = {1}, pages = {e0168390}, pmid = {28045919}, issn = {1932-6203}, support = {W 1241/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Adult ; Anthropometry ; Bacteroidetes/classification/isolation &amp; purification ; Case-Control Studies ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Pilot Projects ; Polycystic Ovary Syndrome/metabolism/*microbiology ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics ; Real-Time Polymerase Chain Reaction ; Surveys and Questionnaires ; Tenericutes/classification/isolation &amp; purification ; }, abstract = {BACKGROUND: Polycystic ovary syndrome (PCOS) is a common female endocrinopathy of unclear origin characterized by hyperandrogenism, oligo-/anovulation, and ovarian cysts. Women with PCOS frequently display overweight, insulin resistance, and systemic low-grade inflammation. We hypothesized that endotoxemia resulting from a leaky gut is associated with inflammation, insulin resistance, fat accumulation, and hyperandrogenemia in PCOS. In this pilot study, we compared the stool microbiome, gut permeability, and inflammatory status of women with PCOS and healthy controls.<br><br>METHODS: 16S rRNA gene amplicon sequencing was performed on stool samples from 24 PCOS patients and 19 healthy controls. Data processing and microbiome analysis were conducted in mothur and QIIME using different relative abundance cut-offs. Gut barrier integrity, endotoxemia, and inflammatory status were evaluated using serum and stool markers and associations with reproductive, metabolic, and anthropometric parameters were investigated.<br><br>RESULTS: The stool microbiome of PCOS patients showed a lower diversity and an altered phylogenetic composition compared to controls. We did not observe significant differences in any taxa with a relative abundance>1%. When looking at rare taxa, the relative abundance of bacteria from the phylum Tenericutes, the order ML615J-28 (phylum Tenericutes) and the family S24-7 (phylum Bacteroidetes) was significantly lower and associated with reproductive parameters in PCOS patients. Patients showed alterations in some, but not all markers of gut barrier function and endotoxemia.<br><br>CONCLUSION: Patients with PCOS have a lower diversity and an altered phylogenetic profile in their stool microbiome, which is associated with clinical parameters. Gut barrier dysfunction and endotoxemia were not driving factors in this patient cohort, but may contribute to the clinical phenotype in certain PCOS patients.}, }
@article {pmid28042926, year = {2016}, author = {Sirisinha, S}, title = {The potential impact of gut microbiota on your health:Current status and future challenges.}, journal = {Asian Pacific journal of allergy and immunology}, volume = {34}, number = {4}, pages = {249-264}, doi = {10.12932/AP0803}, pmid = {28042926}, issn = {0125-877X}, mesh = {*Gastrointestinal Microbiome ; Humans ; }, abstract = {Our health and probably also our behaviors and mood depend not only on what we eat or what we do (lifestyle behaviors), but also on what we host. It is well established for decades that all vertebrates including humans are colonized by a wide array of bacteria, fungi, eukaryotic parasites and viruses, and that, at steady state (homeostasis), this community of microbes establishes a friendly mutual relationship with the host. The term microbiota was originally meant to represent an ecological community of commensals and potentially pathogenic microbes that live within our bodies, but it is now used interchangeably with the term microbiome which was initially meant to represent a collective genome of the microbiota. Although the number of microbes that live in or on our body was previously estimated to outnumber that of their hosts by 10 to 1, the latest estimate put the ratio to be closer to 1:1. On the other hand, their collective genomes (microbiome) outnumber those of the host by 100-200 times. It is not surprising therefore that these microbes not only provide the host with a variety of metabolic impact, but can also modulate tissue integrity and immune defense, all of which lead to a healthy ecosystem (symbiosis) that is unfavorable for colonization and invasion of pathogens. Microbiota is well known for its role in development and education of immune system. However, its link with diseases is less known and it is only recently that there is a surge of interest in the potential impact of microbiota on human health and disease. The diversity and composition of microbiota (healthy microbiota profile) are dynamics, depending not only on the host physical status, genotype and immune phenotype, but also on the environmental factors like diet, antibiotic usage and lifestyle behaviors. These environmental factors may adversely alter gut ecosystem (dysbiosis) that is frequently associated with increased susceptibility to infections as well as to non-communicable diseases like obesity, metabolic syndromes (e.g., diabetes and cardiovascular diseases), allergy and other inflammatory diseases. Emerging evidence from more recent studies also demonstrate the existence of a bidirectional communication route linking gut and microbiota with brain, thus suggesting that these microbes may play a role in neurological disorders as well as in host perception, behavior and emotional response. However, whether the observed alteration of the microbiota profile in these diverse conditions is the cause or the consequence of the disease remains to be established. These observations imply that it may be possible to design new strategies for the management of diseases by manipulating gut microbiota. The common practice now available is the use of probiotics to rehabilitate gut ecosystem. The microbiota-based therapeutics like fecal transplantation for the treatment of recurrent antibiotic-resistant Clostridium difficile infection is now under clinical trial and reported to be highly successful. In the next decade, we will probably see even more exciting approaches, for example, using advanced microbiota engineering technologies to create "intelligent" or "smart" bacteria for use in diagnosis, prevention, prediction and treatment of inflammatory diseases and possibly of some gastrointestinal cancers. The microbiota-based therapeutics together with personalized medicine may be the most accurate and optimal strategy for the future treatment of some difficult-to-manage diseases. However, many challenges remain to be solved before the translational potential of this new knowledge can be implemented clinically. In this review, I highlight some important recent developments and advances that contribute to our understanding in the role of microbiota in human health and disease and on how to best manipulate the microbiome to promote greater human health.}, }
@article {pmid28042242, year = {2017}, author = {Park, L and Mone, A and Price, JC and Tzimas, D and Hirsh, J and Poles, MA and Malter, L and Chen, LA}, title = {Perceptions of fecal microbiota transplantation for Clostridium difficile infection: factors that predict acceptance.}, journal = {Annals of gastroenterology}, volume = {30}, number = {1}, pages = {83-88}, pmid = {28042242}, issn = {1108-7471}, abstract = {BACKGROUND: Despite the effectiveness of fecal microbiota transplantation (FMT) for treating recurrent Clostridium difficile (C. difficile) infection, some patients are reluctant to accept this therapy. Our study examined attitudes towards FMT and factors that contribute to patients' acceptance of this treatment.<br><br>METHODS: We distributed patient surveys at a Veterans Affairs hospital, a public hospital, and an academic faculty practice. Multivariable logistic regression was performed, adjusting for factors associated with FMT acceptance on univariate analysis and prior experience with C. difficile infection.<br><br>RESULTS: Of 267 patients, only 12% knew of FMT prior to the survey, but 77% would undergo the procedure if medically indicated. On multivariable analysis, those with children and with college degrees or higher were more likely to agree to FMT (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.02-4.35; OR 2.27, 95% CI 1.11-4.60 respectively). Sixty-five respondents (71%) chose colonoscopy as the preferred vehicle for FMT, while nasogastric tube was least preferred. Disease transmission was the most common concern (30%, n=242), and FMT success rate was the least selected concern (9.1%).<br><br>CONCLUSIONS: Most patients in a diverse sample of gastroenterology clinics had no prior knowledge of FMT, but were receptive to the procedure. Having children and higher education levels were predictors for FMT acceptance. Our findings suggest that barriers to FMT utilization may be overcome with counseling about safety concerns. More data on the risk of transmitting diseases or clinical characteristics, such as obesity, through FMT are needed and will be important for the acceptance of this procedure.}, }
@article {pmid28041931, year = {2017}, author = {Griffin, NW and Ahern, PP and Cheng, J and Heath, AC and Ilkayeva, O and Newgard, CB and Fontana, L and Gordon, JI}, title = {Prior Dietary Practices and Connections to a Human Gut Microbial Metacommunity Alter Responses to Diet Interventions.}, journal = {Cell host &amp; microbe}, volume = {21}, number = {1}, pages = {84-96}, pmid = {28041931}, issn = {1934-6069}, support = {K05 AA017688/AA/NIAAA NIH HHS/United States ; P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK030292/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; P30 DK056341/DK/NIDDK NIH HHS/United States ; T32 DK007120/DK/NIDDK NIH HHS/United States ; //Wellcome Trust/United Kingdom ; R37 DK030292/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*classification/genetics/*metabolism ; Caloric Restriction ; *Diet ; Feces/microbiology ; *Feeding Behavior ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Germ-Free Life ; Humans ; Male ; Mice ; }, abstract = {Ensuring that gut microbiota respond consistently to prescribed dietary interventions, irrespective of prior dietary practices (DPs), is critical for effective nutritional therapy. To address this, we identified DP-associated gut bacterial taxa in individuals either practicing chronic calorie restriction with adequate nutrition (CRON) or without dietary restrictions (AMER). When transplanted into gnotobiotic mice, AMER and CRON microbiota responded predictably to CRON and AMER diets but with variable response strengths. An individual's microbiota is connected to other individuals' communities ("metacommunity") by microbial exchange. Sequentially cohousing AMER-colonized mice with two different groups of CRON-colonized mice simulated metacommunity effects, resulting in enhanced responses to a CRON diet intervention and changes in several metabolic features in AMER animals. This response was driven by an influx of CRON DP-associated taxa. Certain DPs may impair responses to dietary interventions, necessitating the introduction of diet-responsive bacterial lineages present in other individuals and identified using the strategies described.}, }
@article {pmid28039277, year = {2017}, author = {Mahieu, R and Cassisa, V and Godefroy, A and Joly-Guillou, ML and Eveillard, M}, title = {Effect of faecal microbiota transplantation on mouse gut colonization with carbapenemase-producing Escherichia coli.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {72}, number = {4}, pages = {1260-1262}, doi = {10.1093/jac/dkw540}, pmid = {28039277}, issn = {1460-2091}, mesh = {Animals ; Bacterial Proteins/*metabolism ; Escherichia coli/*growth &amp; development/*metabolism ; Escherichia coli Infections/*microbiology/*therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Mice ; beta-Lactamases/*metabolism ; }, }
@article {pmid28039159, year = {2017}, author = {Knoll, RL and Forslund, K and Kultima, JR and Meyer, CU and Kullmer, U and Sunagawa, S and Bork, P and Gehring, S}, title = {Gut microbiota differs between children with Inflammatory Bowel Disease and healthy siblings in taxonomic and functional composition: a metagenomic analysis.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {312}, number = {4}, pages = {G327-G339}, doi = {10.1152/ajpgi.00293.2016}, pmid = {28039159}, issn = {1522-1547}, mesh = {Adolescent ; Child ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Intestinal Mucosa/*microbiology ; Male ; *Metagenome ; Siblings ; Young Adult ; }, abstract = {Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn's disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U-test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii, were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option.NEW &amp; NOTEWORTHY In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD.}, }
@article {pmid28031550, year = {2016}, author = {Navarrete-Sandoval, RH and Servín-Rojas, M}, title = {Bug Smash, Bug Splash: A Case Report of an Unusual Transmission of American Trypanosomiasis with a Brief Review of the Literature.}, journal = {The American journal of case reports}, volume = {17}, number = {}, pages = {993-996}, pmid = {28031550}, issn = {1941-5923}, mesh = {Adult ; Animals ; Chagas Disease/*diagnosis/parasitology/*transmission ; Edema/parasitology ; Fever/parasitology ; Headache/parasitology ; Humans ; Male ; Neglected Diseases ; Nifurtimox/*therapeutic use ; Treatment Outcome ; Triatominae/parasitology ; Trypanocidal Agents/*therapeutic use ; Trypanosoma cruzi/*parasitology ; }, abstract = {BACKGROUND Chagas disease is a chronic parasitosis transmitted by the inoculation of infected triatomine feces into wounds or conjunctival sac, transfusion, congenitally, organ transplantation, and ingestion of contaminated food. The disease is classified into an acute and chronic phase; the latter is a life-long infection that can be asymptomatic or progress to cardiac or digestive complications. CASE REPORT We report a case of acute-phase Chagas disease, transmitted by the splash of gut content from an infected triatomine into the conjunctival mucosa. CONCLUSIONS The diagnosis of Chagas disease is made by the direct visualization of the parasite in blood smears during the acute phase of the disease; during the chronic phase of the disease the diagnosis is made by the detection of IgG antibodies. Parasitological cure can be achieved in up to 80% of the cases in acute phase of the disease, in contrast with less than 30% during the chronic phase.}, }
@article {pmid28030369, year = {2017}, author = {Hov, JR and Kummen, M}, title = {Intestinal microbiota in primary sclerosing cholangitis.}, journal = {Current opinion in gastroenterology}, volume = {33}, number = {2}, pages = {85-92}, doi = {10.1097/MOG.0000000000000334}, pmid = {28030369}, issn = {1531-7056}, mesh = {Animals ; Case-Control Studies ; Cholangitis, Sclerosing/genetics/metabolism/*microbiology ; Disease Models, Animal ; *Gastrointestinal Microbiome/genetics ; Genetic Predisposition to Disease ; Humans ; Metabolomics ; }, abstract = {PURPOSE OF REVIEW: Alterations of the gut-liver axis have been linked to the pathogenesis of primary sclerosing cholangitis (PSC) since the disease was first described. The purpose of this review is to discuss multiple recent studies on the intestinal microbiota in human PSC and experimental models of this disease.<br><br>RECENT FINDINGS: Data are available from eight cross-sectional studies of human PSC, which include a variable number of patients (n&#x200a;=&#x200a;11-85), material (mucosal or fecal), and microbiota profiling methodology. Despite the heterogeneity of the studies, a pattern of differences is observed that could represent a theme or signature of the PSC gut microbiota, characterized by low diversity and with alterations in multiple bacterial taxa. In experimental models of PSC, re-derivation of animals into germ-free facilities may either aggravate or attenuate the disease, depending on host genetics and putative disease mechanisms (e.g., fibrotic or immune-driven processes, respectively).<br><br>SUMMARY: The present data provide a strong rationale to explore the functional consequences of the observed gut microbial alterations and their influence on the pathogenesis in PSC. Studies of gut microbiota as biomarker and treatment target may potentially also lead to early translation into clinical practice.}, }
@article {pmid28029471, year = {2017}, author = {Prior, AR and Kevans, D and McDowell, L and Cudmore, S and Fitzpatrick, F}, title = {Treatment of Clostridium difficile infection: a national survey of clinician recommendations and the use of faecal microbiota transplantation.}, journal = {The Journal of hospital infection}, volume = {95}, number = {4}, pages = {438-441}, doi = {10.1016/j.jhin.2016.10.004}, pmid = {28029471}, issn = {1532-2939}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Colitis/microbiology/*therapy ; Fecal Microbiota Transplantation/*statistics &amp; numerical data ; Guideline Adherence ; Guidelines as Topic ; Humans ; Ireland ; Surveys and Questionnaires ; }, abstract = {Adherence to Clostridium difficile infection treatment guidelines is associated with lower recurrence rates and mortality as well as cost savings. This survey of Irish clinicians indicates that patients are managed using a variety of approaches. Faecal microbiota transplantation is potentially underused despite its recommendation in national and European guidelines.}, }
@article {pmid28028357, year = {2016}, author = {Navarro, F and Liu, Y and Rhoads, JM}, title = {Can probiotics benefit children with autism spectrum disorders?.}, journal = {World journal of gastroenterology}, volume = {22}, number = {46}, pages = {10093-10102}, pmid = {28028357}, issn = {2219-2840}, mesh = {Abdominal Pain/drug therapy/immunology/microbiology ; Autism Spectrum Disorder/immunology/*microbiology ; Child ; Constipation/*drug therapy/immunology/microbiology ; Diarrhea/*drug therapy/immunology/microbiology ; Gastrointestinal Diseases/*drug therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Humans ; Inflammation ; Probiotics/*therapeutic use ; }, abstract = {Children with autism are commonly affected by gastrointestinal problems such as abdominal pain, constipation and diarrhea. In recent years, there has been a growing interest in the use of probiotics in this population, as it hypothetically may help to improve bowel habits and the behavioral and social functioning of these individuals. The gut microbiome plays an important role in the pathophysiology of organic as well as functional gastrointestinal disorders. Microbial modification with the use of antibiotics, probiotics, and fecal transplantation have been effective in the treatment of conditions such as recurrent Clostridium difficile infection, pouchitis, and irritable bowel syndrome. The present review presents a number of reported clinical, immunological and microbiome-related changes seen in children with autism compared to normally developed children. It also discusses gut inflammation, permeability concerns, and absorption abnormalities that may contribute to these problems. Most importantly, it discusses evidence, from human and animal studies, of a potential role of probiotics in the treatment of gastrointestinal symptoms in children with autism.}, }
@article {pmid28027582, year = {2017}, author = {Ren, YD and Ye, ZS and Yang, LZ and Jin, LX and Wei, WJ and Deng, YY and Chen, XX and Xiao, CX and Yu, XF and Xu, HZ and Xu, LZ and Tang, YN and Zhou, F and Wang, XL and Chen, MY and Chen, LG and Hong, MZ and Ren, JL and Pan, JS}, title = {Fecal microbiota transplantation induces hepatitis B virus e-antigen (HBeAg) clearance in patients with positive HBeAg after long-term antiviral therapy.}, journal = {Hepatology (Baltimore, Md.)}, volume = {65}, number = {5}, pages = {1765-1768}, doi = {10.1002/hep.29008}, pmid = {28027582}, issn = {1527-3350}, mesh = {Adult ; Antiviral Agents/*therapeutic use ; Case-Control Studies ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/immunology ; Hepatitis B e Antigens/*analysis ; Hepatitis B, Chronic/immunology/*therapy/*virology ; Humans ; Male ; }, }
@article {pmid28027214, year = {2017}, author = {Busoni, VB and Lemale, J and Dubern, B and Frangi, F and Bourgeois, P and Orsi, M and Badens, C and Fabre, A}, title = {IBD-Like Features in Syndromic Diarrhea/Trichohepatoenteric Syndrome.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {64}, number = {1}, pages = {37-41}, doi = {10.1097/MPG.0000000000001218}, pmid = {28027214}, issn = {1536-4801}, mesh = {Anti-Inflammatory Agents/therapeutic use ; Biological Therapy ; Colitis/etiology ; Colon/*pathology ; Diarrhea/etiology ; Diarrhea, Infantile/drug therapy/metabolism/*pathology/therapy ; Facies ; Feces/chemistry ; Female ; Fetal Growth Retardation/drug therapy/metabolism/*pathology/therapy ; Gastroenteritis/*etiology ; Hair ; Hair Diseases/drug therapy/metabolism/*pathology/therapy ; Humans ; Ileitis/etiology ; Immunologic Factors/therapeutic use ; Infant ; Infant, Newborn ; Inflammatory Bowel Diseases/drug therapy/metabolism/*pathology ; Intestine, Small/*pathology ; Leukocyte L1 Antigen Complex/*metabolism ; Male ; Mesalamine/therapeutic use ; Syndrome ; }, abstract = {BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) (inflammatory bowel disease [IBD] before 6 years of age) may manifest as a monogenic disease affecting the gastrointestinal tract. Syndromic diarrhea/trichohepatoenteric syndrome (SD/THE), a rare disorder caused by alteration of a complex involved in RNA degradation, has been reported to present with some degree of colitis and in some cases an IBD-like presentation.<br><br>METHODS: We reviewed clinical and biological data of 4 previously published cases and added detailed data of 2 new cases of SD/THE with an IBD-like presentation.<br><br>RESULTS: All the 6 patients presented with typical intractable diarrhea and hair abnormalities. The colon was affected in all of the patients: 1 had ileitis, 2 had panenteritis, and 2 presented with perianal disease. Fecal calprotectin level and erythrosedimentation rate were elevated in 2 cases each. All the therapeutic classes of IBD treatment (mesalazine, steroids, immunomodulators, and biological therapy) were used in the 6 cases. In 2 patients, treatment had no effect. Three showed a partial effect, and 1 patient sustained only a transient effect.<br><br>CONCLUSIONS: SD/THE can have a similar presentation as VEOIBD, often as pancolitis. IBD treatments appear to have little efficacy for SD/THE, suggesting a different pathogenesis for the IBD-like features in SD/THE compared with classical IBD.}, }
@article {pmid28011612, year = {2017}, author = {Hota, SS and Sales, V and Tomlinson, G and Salpeter, MJ and McGeer, A and Coburn, B and Guttman, DS and Low, DE and Poutanen, SM}, title = {Oral Vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection: An Open-Label, Randomized Controlled Trial.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {64}, number = {3}, pages = {265-271}, doi = {10.1093/cid/ciw731}, pmid = {28011612}, issn = {1537-6591}, mesh = {Administration, Oral ; Adult ; Aged ; Anti-Bacterial Agents/*administration &amp; dosage/therapeutic use ; *Clostridioides difficile ; Diarrhea/drug therapy/microbiology/*therapy ; Enterocolitis, Pseudomembranous/drug therapy/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Microbiota ; Middle Aged ; Ontario ; Recurrence ; Vancomycin/*administration &amp; dosage/therapeutic use ; Young Adult ; }, abstract = {BACKGROUND: Fecal transplantation (FT) is a promising treatment for recurrent Clostridium difficile infection (CDI), but its true effectiveness remains unknown. We compared 14 days of oral vancomycin followed by a single FT by enema with oral vancomycin taper (standard of care) in adult patients experiencing acute recurrence of CDI.<br><br>METHODS: In a phase 2/3, single-center, open-label trial, participants from Ontario, Canada, experiencing recurrence of CDI were randomly assigned in a 1:1 ratio to 14 days of oral vancomycin treatment followed by a single 500-mL FT by enema, or a 6-week taper of oral vancomycin. Patients with significant immunocompromise, history of fulminant CDI, or irreversible bleeding disorders were excluded. The primary endpoint was CDI recurrence within 120 days. Microbiota analysis was performed on fecal filtrate from donors and stool samples from FT recipients, as available.<br><br>RESULTS: The study was terminated at the interim analysis after randomizing 30 patients. Nine of 16 (56.2%) patients who received FT and 5 of 12 (41.7%) in the vancomycin taper group experienced recurrence of CDI, corresponding with symptom resolution in 43.8% and 58.3%, respectively. Fecal microbiota analysis of 3 successful FT recipients demonstrated increased diversity. A futility analysis did not support continuing the study. Adverse events were similar in both groups and uncommon.<br><br>CONCLUSIONS: In patients experiencing an acute episode of recurrent CDI, a single FT by enema was not significantly different from oral vancomycin taper in reducing recurrent CDI. Further research is needed to explore optimal donor selection, FT preparation, route, timing, and number of administrations.<br><br>CLINICAL TRIALS REGISTRATION: NCT01226992.}, }
@article {pmid28011611, year = {2017}, author = {Johnson, S and Gerding, DN}, title = {Fecal Fixation: Fecal Microbiota Transplantation for Clostridium difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {64}, number = {3}, pages = {272-274}, doi = {10.1093/cid/ciw735}, pmid = {28011611}, issn = {1537-6591}, support = {I01 BX002449/BX/BLRD VA/United States ; }, mesh = {*Clostridioides difficile ; Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Vancomycin ; }, }
@article {pmid28008843, year = {2016}, author = {Durif-Bruckert, C}, title = {[Intestinal microbiota and emergence of new representations of the body: a psychosocial approach].}, journal = {Medecine sciences : M/S}, volume = {32}, number = {11}, pages = {1009-1015}, doi = {10.1051/medsci/20163211018}, pmid = {28008843}, issn = {1958-5381}, mesh = {Body Image/psychology ; Digestion/*physiology ; Fecal Microbiota Transplantation/psychology ; Gastrointestinal Microbiome/*physiology ; *Human Body ; Humans ; Psychology ; }, abstract = {In view of the growing importance attached to the gut microbiota in preventive medicine and treatment, it would seem essential to identify and analyse the modalities of its representation in a psychosocial approach. In the first part of this article, we will discuss the renewal of representations of the digestive tract brought about by scientific discourse on the gut microbiota, mainly regarding the anthropological status of the intestines and faeces. Then in the second part we will focus on ways of taking advantage of the variable nature of the microbiota by food choices, and we will also focus on therapeutic approaches that use transplantations of faecal matter, and the ensuing loss of privacy entailed (an anthropological notion of defil).}, }
@article {pmid28008842, year = {2016}, author = {Dodet, B}, title = {[Microbiota and representations of the human body].}, journal = {Medecine sciences : M/S}, volume = {32}, number = {11}, pages = {1003-1008}, doi = {10.1051/medsci/20163211017}, pmid = {28008842}, issn = {1958-5381}, mesh = {*Body Image/psychology ; Digestion/physiology ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/*psychology/trends ; Gastrointestinal Microbiome/*physiology ; *Human Body ; Humans ; Intestines/microbiology/physiology ; }, abstract = {Although the presence of an intestinal flora has been known for a long time, the discovery of the role of gut microbiota in human health and disease has been widely recognized as one of the most important advances in the recent years. Chronic diseases may result from dysbiosis, i.e. a disruption of the balance within the bacterial population hosted by the human body. These developments open new prospects in terms of prevention and treatment, including the design of adapted diets, the development of functional foods and fecal transplantation. These discoveries have profoundly altered our view of microbes, of health and disease, of self and non-self, as well as our representations of the body and its relationship with its ecosystem. Gut microbiota is now generally considered as an organ in its own right. A model of the "microbiotic person" thus arises, in which the human organism is defined as an ecosystem, a chimeric superorganism with a double genome, both human and microbial. Thought should be given to the way in which these new paradigms modify lay perceptions of the human body.}, }
@article {pmid28008840, year = {2016}, author = {Lagier, JC and Raoult, D}, title = {[Fecal microbiota transplantation: indications and perspectives].}, journal = {Medecine sciences : M/S}, volume = {32}, number = {11}, pages = {991-997}, doi = {10.1051/medsci/20163211015}, pmid = {28008840}, issn = {1958-5381}, mesh = {Animals ; Antibiosis/physiology ; Clostridioides difficile/pathogenicity ; Clostridium Infections/microbiology/therapy ; Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation/*methods/*statistics &amp; numerical data ; Host-Pathogen Interactions ; Humans ; Recurrence ; }, abstract = {Fecal transplantation demonstrated in a randomized trial its superiority compared to antibiotics in recurrent Clostridium difficile (CD) infections. Used in first-line treatment, it has reduced the mortality of patients suffering of CD infections caused by ribotype 027 and made it possible to cure patients with severe manifestations of CD infections caused by other ribotypes. The use of frozen microbiota, now validated, facilitates fecal microbiota transplantation. In addition, the frozen microbiota capsules have proven their efficiency. Other indications such as the digestive decolonization of multidrug-resistant bacteria are emerging. Finally, a better knowledge of the gastrointestinal microbiota will lead in the future to new targeted therapies in many indications.}, }
@article {pmid28008827, year = {2016}, author = {Gilgenkrantz, H and Teillaud, JL}, title = {[The coordinators' word].}, journal = {Medecine sciences : M/S}, volume = {32}, number = {11}, pages = {921}, doi = {10.1051/medsci/20163211002}, pmid = {28008827}, issn = {1958-5381}, mesh = {Fecal Microbiota Transplantation/trends ; Host-Pathogen Interactions/immunology ; Humans ; Metagenomics ; Microbiota/*physiology ; Prebiotics/microbiology ; Probiotics/therapeutic use ; *Symbiosis/genetics ; }, }
@article {pmid28008784, year = {2017}, author = {Vemuri, RC and Gundamaraju, R and Shinde, T and Eri, R}, title = {Therapeutic interventions for gut dysbiosis and related disorders in the elderly: antibiotics, probiotics or faecal microbiota transplantation?.}, journal = {Beneficial microbes}, volume = {8}, number = {2}, pages = {179-192}, doi = {10.3920/BM2016.0115}, pmid = {28008784}, issn = {1876-2891}, mesh = {Aged ; Aging ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/drug effects ; Cross Infection/epidemiology/microbiology ; Dietary Supplements/microbiology ; Dysbiosis/*therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Gastroenteritis/chemically induced/microbiology/*therapy ; Gastrointestinal Microbiome ; Humans ; Prebiotics/*administration &amp; dosage ; Probiotics/*therapeutic use ; }, abstract = {Ageing and physiological functions of the human body are inversely proportional to each other. The gut microbiota and host immune system co-evolve from infants to the elderly. Ageing is accompanied by a decline in gut microbial diversity, immunity and metabolism, which increases susceptibility to infections. Any compositional change in the gut is directly linked to gastrointestinal disorders, obesity and metabolic diseases. Increase in opportunistic pathogen invasion in the gut like Clostridium difficile leading to C. difficile infection is more common in the elderly population. Frequent hospitalisation and high prevalence of nosocomial infections with the ageing is also well documented. Long-term utilisation of broad-spectrum antibiotic therapy is being followed in order to control these infections. Nosocomial infections and antibiotic therapy in combination or alone is leading to gastroenteritis followed by Clostridium associated diarrhoea or antibiotic associated diarrhoea. Above all, use of broad-spectrum antibiotics is highly debated all over the world due to growing antimicrobial resistance. The use of narrow spectrum antibiotics could be helpful to some extent. Dietary supplementation of probiotics with prebiotics (synbiotics) or without prebiotics has improved gut commensal diversity and regulated the immune system. The recent emergence of faecal microbiota transplantation has played an important role in treating recurrent Clostridium associated diarrhoea. This review focuses on various therapeutic interventions for gut dysbiosis and gastrointestinal diseases in the elderly. The possible mechanism for antimicrobial resistance and mechanism of action of probiotics are also discussed in detail.}, }
@article {pmid28008631, year = {2017}, author = {Segal, JP and Ding, NS and Worley, G and Mclaughlin, S and Preston, S and Faiz, OD and Clark, SK and Hart, AL}, title = {Systematic review with meta-analysis: the management of chronic refractory pouchitis with an evidence-based treatment algorithm.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {45}, number = {5}, pages = {581-592}, doi = {10.1111/apt.13905}, pmid = {28008631}, issn = {1365-2036}, mesh = {Algorithms ; Anal Canal/surgery ; Colitis, Ulcerative/*surgery ; Colonic Pouches ; Humans ; Pouchitis/etiology/*therapy ; Proctocolectomy, Restorative/*adverse effects ; Remission Induction ; Tacrolimus/administration &amp; dosage ; }, abstract = {BACKGROUND: Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) is considered the procedure of choice in patients with ulcerative colitis (UC) refractory to medical therapy. The incidence of pouchitis is 40% at 5 years. Ten to 15% of patients with pouchitis experience chronic pouchitis.<br><br>AIM: To determine the efficacy of medical therapies for the treatment of chronic refractory pouchitis in patients undergoing IPAA for UC.<br><br>METHODS: A systematic computer-assisted search of the on-line bibliographic database MEDLINE and EMBASE was performed between 1966 and February 2016. All original studies reporting remission rates following medical treatment for chronic pouchitis were included. All study designs were considered. Remission was defined according to the individual study. Remission endpoints ranged from 15 days to 10 weeks. Chronic pouchitis was defined by each study.<br><br>RESULTS: Twenty-one papers were considered eligible. Results from all studies combined suggested that overall remission was obtained in 59% of patients (95% CI: 44-73%). Antibiotics significantly induced remission in patients with chronic pouchitis with 74% remission rate (95% CI:56-93%), (P < 0.001). Biologics significantly induced remission in patients with chronic pouchitis with 53% remission rate (95% CI:30-76%), (P < 0.001). Steroids, bismuth, elemental diet and tacrolimus all can induce remission but failed to achieve significance. Faecal microbiota transplantation in a single study was not found to achieve remission.<br><br>CONCLUSIONS: Treatment of chronic refractory pouchitis remains difficult and is largely empirical. Larger randomised controlled trials will help aid the management of chronic pouchitis.}, }
@article {pmid28004036, year = {2016}, author = {Tambo, A and Roshan, MH and Pace, NP}, title = {The Microbial Hypothesis: Contributions of Adenovirus Infection and Metabolic Endotoxaemia to the Pathogenesis of Obesity.}, journal = {International journal of chronic diseases}, volume = {2016}, number = {}, pages = {7030795}, pmid = {28004036}, issn = {2356-6981}, abstract = {The global obesity epidemic, dubbed "globesity" by the World Health Organisation, is a pressing public health issue. The aetiology of obesity is multifactorial incorporating both genetic and environmental factors. Recently, epidemiological studies have observed an association between microbes and obesity. Obesity-promoting microbiome and resultant gut barrier disintegration have been implicated as key factors facilitating metabolic endotoxaemia. This is an influx of bacterial endotoxins into the systemic circulation, believed to underpin obesity pathogenesis. Adipocyte dysfunction and subsequent adipokine secretion characterised by low grade inflammation, were conventionally attributed to persistent hyperlipidaemia. They were thought of as pivotal in perpetuating obesity. It is now debated whether infection and endotoxaemia are also implicated in initiating and perpetuating low grade inflammation. The fact that obesity has a prevalence of over 600 million and serves as a risk factor for chronic diseases including cardiovascular disease and type 2 diabetes mellitus is testament to the importance of exploring the role of microbes in obesity pathobiology. It is on this basis that Massachusetts General Hospital is sponsoring the Faecal Microbiota Transplant for Obesity and Metabolism clinical trial, to study the impact of microbiome composition on weight. The association of microbes with obesity, namely, adenovirus infection and metabolic endotoxaemia, is reviewed.}, }
@article {pmid28003123, year = {2017}, author = {van Beek, J and van der Eijk, AA and Fraaij, PL and Caliskan, K and Cransberg, K and Dalinghaus, M and Hoek, RA and Metselaar, HJ and Roodnat, J and Vennema, H and Koopmans, MP}, title = {Chronic norovirus infection among solid organ recipients in a tertiary care hospital, the Netherlands, 2006-2014.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {23}, number = {4}, pages = {265.e9-265.e13}, doi = {10.1016/j.cmi.2016.12.010}, pmid = {28003123}, issn = {1469-0691}, mesh = {Adolescent ; Adult ; Aged ; Caliciviridae Infections/diagnosis/*epidemiology/*etiology ; Child ; Child, Preschool ; Chronic Disease ; Female ; Genes, Viral ; Humans ; Immunocompromised Host ; Male ; Middle Aged ; Netherlands/epidemiology ; *Norovirus/genetics/isolation &amp; purification ; *Organ Transplantation/adverse effects ; Retrospective Studies ; *Tertiary Care Centers ; *Transplant Recipients ; Virus Shedding ; Young Adult ; }, abstract = {OBJECTIVES: Immunocompromised patients can suffer prolonged norovirus symptoms and virus shedding for many years. Little is known about the prevalence of chronic norovirus infection among solid organ transplant (SOT) recipients. In this study, 2182 SOT recipients were retrospectively tested for chronic norovirus infection.<br><br>METHODS: The first and last norovirus positive faecal samples of SOT recipients were sequenced to distinguish between persisting infection and re-infection. Patient charts were reviewed to obtain data on health status and treatments.<br><br>RESULTS: In all, 101 of 2182 (4.6%) recipients were norovirus infected and 23 (22.8%) of these developed chronic norovirus infection. Chronic norovirus infection was found among allogeneic heart, kidney and lung transplant recipients. The median shedding period at the end of the study period was 218 days (range 32-1164 days).<br><br>CONCLUSIONS: This study shows that chronic norovirus infection is not a rare phenomenon among SOT recipients in a tertiary-care hospital. Further research is needed to study the risk of norovirus transmission to other immunocompromised patients in the hospital and to the general population.}, }
@article {pmid28001467, year = {2017}, author = {Fischer, M and Sipe, B and Cheng, YW and Phelps, E and Rogers, N and Sagi, S and Bohm, M and Xu, H and Kassam, Z}, title = {Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: A promising treatment approach.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {289-302}, pmid = {28001467}, issn = {1949-0984}, support = {//CIHR/Canada ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/*therapy ; Cohort Studies ; Colectomy ; Colonoscopy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Follow-Up Studies ; Freezing ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Risk Factors ; Survival Rate ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {Severe and severe-complicated Clostridium difficile infection (CDI) is associated with high morbidity and mortality. Colectomy is standard of care; however, post-surgical mortality rates approach 50%. Case reports suggest fecal microbiota transplant (FMT) is a promising treatment of severe and severe-complicated disease but there is a paucity of data. Here, we present a single center experience with a novel sequential FMT protocol for patients refractory to maximal medical therapy. This approach consists of at least one FMT delivered via colonoscopy with criteria for repeat FMT and continued vancomycin therapy based on clinical response and pseudomembranes. Our cohort included 57 consecutive inpatients diagnosed with severe or severe-complicated CDI and treated with FMT. Overall, 91% (52/57) experienced clinical cure at 1 month with a 100% cure rate among severe CDI (n = 19) patients and an 87% cure rate for severe-complicated CDI (n = 33) patients. For the cohort, the survival rate was 94.7% at 1 month and 78.6% at 3 months. There were no serious adverse events related to FMT including no procedure-related complications or perforation. There was no difference in outcome between fresh or frozen fecal material. Sequential FMT for inpatients with severe or severe-complicated CDI is promising and may be preferred over colectomy in certain patients.}, }
@article {pmid28000680, year = {2017}, author = {Keshteli, AH and Millan, B and Madsen, KL}, title = {Pretreatment with antibiotics may enhance the efficacy of fecal microbiota transplantation in ulcerative colitis: a meta-analysis.}, journal = {Mucosal immunology}, volume = {10}, number = {2}, pages = {565-566}, doi = {10.1038/mi.2016.123}, pmid = {28000680}, issn = {1935-3456}, mesh = {Anti-Bacterial Agents ; *Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Feces ; Gastrointestinal Microbiome ; Humans ; Treatment Outcome ; }, }
@article {pmid28000190, year = {2016}, author = {Ge, X and Ding, C and Gong, J and Tian, H and Wei, Y and Chen, Q and Gu, L and Li, N}, title = {[Short-term efficacy on fecal microbiota transplantation combined with soluble dietary fiber and probiotics in the treatment of slow transit constipation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {19}, number = {12}, pages = {1355-1359}, pmid = {28000190}, issn = {1671-0274}, mesh = {Adult ; Aged ; *Constipation ; Defecation ; Dietary Fiber ; *Fecal Microbiota Transplantation ; Feces ; Female ; Gastrointestinal Diseases ; Humans ; Male ; Microbiota ; Middle Aged ; Pectins ; Probiotics ; Quality of Life ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) combined with soluble dietary fiber and probiotics for slow transit constipation(STC).<br><br>METHODS: Twenty-three patients with STC from Jinling Hospital, Medical School of Nanjing University were prospectively enrolled between April 2015 and January 2016. STC patients received FMT combined with soluble dietary fiber and probiotics. Fresh stool(100 g) was immediately mixed in a blender with 500 ml of 0.9% sterile saline for several seconds, which was then filtered through a gauze pad and a decreasing number of gauze screen (2.0 to 0.5 mm). The fecal bacteria suspension was stored frozen at -20centi-degree. The preparation time of FMT material was less than 1 hour. Total time of treatment was 9 days. An initial oral antibiotics(vancomycin 500 mg orally twice per day) was given for 3 consecutive days. Then the fecal microbiota(100 ml) was infused slowly(5 min) through nasojejunal tube for 6 consecutive days. After FMT, patients were recommended to receive soluble dietary fiber (pectin, 8 g/d) and probiotics (bifid triple viable capsules, twice per day) for 4 weeks. Rates of clinical improvement and remission, adverse events, constipation-related symptoms (PAC-SYM scores), bowel movements per week and gastrointestinal quality-of-life index (GIQLI) were recorded during the 12-week follow-up. This study was registered in the Clinical Trials.gov (NCT02016469).<br><br>RESULTS: Among 23 patients, 7 were male, 16 were female, the mean age was (49.6&#xb1;14.7) years, the body mass index was (21.2&#xb1;2.2) kg/m[2], the duration of constipation was (8.3&#xb1;5.9) years, and the defecation frequency was 1.8&#xb1;0.7 per week. Compared with pre-treatment, PAC-SYM scores decreased significantly from 2.3&#xb1;0.5 to 1.3&#xb1;0.4 at week 12 (P<0.01), defecation frequency increased from 1.8&#xb1;0.7 per week to 4.8&#xb1;2.0 per week at week 12 (P<0.01), and patients felt satisfied with improved GIQLI score (from 78.5&#xb1;15.5 to 120.8&#xb1;21.3, P<0.01). During the follow-up, the clinical improvement and remission of STC patients reached 69.6%(16/23) and 52.2%(12/23), respectively. No serious adverse events were observed.<br><br>CONCLUSION: FMT combined with soluble dietary fiber and probiotics is safe and effective in treating slow transit constipation, which can improve the symptom and quality of life significantly.}, }
@article {pmid27999312, year = {2016}, author = {Yang, L and Wang, L and Wang, X and Xian, CJ and Lu, H}, title = {A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis.}, journal = {International journal of molecular sciences}, volume = {17}, number = {12}, pages = {}, pmid = {27999312}, issn = {1422-0067}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Prebiotics ; Probiotics/therapeutic use ; Rats ; Sacroiliac Joint/*pathology ; Spine/*pathology ; Spondylitis, Ankylosing/*microbiology/pathology/*therapy ; }, abstract = {Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the sacroiliac joints and the spine, for which the pathogenesis is thought to be a result of the combination of host genetic factors and environmental triggers. However, the precise factors that determine one's susceptibility to AS remain to be unraveled. With 100 trillion bacteria residing in the mammalian gut having established a symbiotic relation with their host influencing many aspects of host metabolism, physiology, and immunity, a growing body of evidence suggests that intestinal microbiota may play an important role in AS. Several mechanisms have been suggested to explain the potential role of the microbiome in the etiology of AS, such as alterations of intestinal permeability, stimulation of immune responses, and molecular mimicry. In this review, the existing evidence for the involvement of the microbiome in AS pathogenesis was discussed and the potential of intestinal microbiome-targeting strategies in the prevention and treatment of AS was evaluated.}, }
@article {pmid27999162, year = {2016}, author = {Staley, C and Kelly, CR and Brandt, LJ and Khoruts, A and Sadowsky, MJ}, title = {Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent Clostridium difficile Infection following Fecal Microbiota Transplantation.}, journal = {mBio}, volume = {7}, number = {6}, pages = {}, pmid = {27999162}, issn = {2150-7511}, support = {R21 AI114722/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteroidetes/isolation &amp; purification ; Bayes Theorem ; Clinical Trials as Topic ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Diarrhea/microbiology ; Fecal Microbiota Transplantation/*methods/standards ; Feces/*microbiology ; Female ; Firmicutes/isolation &amp; purification ; Gastrointestinal Microbiome ; Healthy Volunteers ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Recurrence ; Remission Induction/methods ; }, abstract = {UNLABELLED: Bacterial communities from subjects treated for recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT), using either heterologous donor stool samples or autologous stool samples, were characterized by Illumina next-generation sequencing. As previously reported, the success of heterologous FMT (90%) was superior to that of autologous FMT (43%) (P = 0.019), and post-FMT intestinal bacterial communities differed significantly between treatment arms (P < 0.001). Subjects cured by autologous FMT typically had greater abundances of the Clostridium XIVa clade and Holdemania bacteria prior to treatment, and the relative abundances of these groups increased significantly after FMT compared to heterologous FMT and pre-FMT samples. The typical shift to post-FMT, donor-like assemblages, featuring high relative abundances of genera within the Bacteroidetes and Firmicutes phyla, was not observed in the autologous FMT subjects. Autologous FMT patient bacterial communities were significantly different in composition than those for heterologous FMT patients and donors (P < 0.001). The SourceTracker program, which employs a Bayesian algorithm to determine source contributions to sink communities, showed that patients initially treated by heterologous FMT had significantly higher percentages of engraftment (i.e., similarity to donor communities, mean value of 74%) compared to those who suffered recurrence following autologous FMT (1%) (P ≤ 0.013). The findings of this study suggest that complete donor engraftment may be not necessary if functionally critical taxa are present in subjects following antibiotic therapy.<br><br>IMPORTANCE: This study provides a detailed characterization of fecal bacterial communities in subjects who participated in a previously published randomized clinical trial to treat recurrent C.&#xa0;difficile infection (rCDI). Bacterial communities were characterized to determine differences between subjects who received fecal bacteria either from healthy donor stool samples or their own stool samples as "placebo" in order to determine which groups of bacteria were most important in achieving a cure. The results of this study suggested that bacteria associated with secondary bile acid metabolism could potentially provide resistance to infection and that complete transfer of healthy donor microorganisms was not necessary to resolve CDI following unsuccessful antibiotic treatment.}, }
@article {pmid27999027, year = {2017}, author = {Staley, C and Vaughn, BP and Graiziger, CT and Sadowsky, MJ and Khoruts, A}, title = {Gut-sparing treatment of urinary tract infection in patients at high risk of Clostridium difficile infection.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {72}, number = {2}, pages = {522-528}, pmid = {27999027}, issn = {1460-2091}, support = {L30 DK099831/DK/NIDDK NIH HHS/United States ; R21 AI114722/AI/NIAID NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Amikacin/adverse effects/*therapeutic use ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Clostridioides difficile/drug effects ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Gentamicins/adverse effects/*therapeutic use ; Humans ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Urinary Tract Infections/microbiology/*therapy ; }, abstract = {BACKGROUND: Recipients of faecal microbiota transplantation (FMT) in treatment of recurrent Clostridium difficile infection (RCDI) remain at markedly increased risk of re-infection with C. difficile with new antibiotic provocations. Urinary tract infections (UTIs) are common indications for antibiotics in these patients, often resulting in C. difficile re-infection.<br><br>METHODS: We present a case series of 19 patients treated with parenteral aminoglycosides for UTI following FMT for RCDI. A 3&#x2005;day outpatient regimen of once-daily intramuscular administration of gentamicin was used to treat 18 consecutive FMT recipients with uncomplicated UTI. One other patient was treated for a complicated UTI with intravenous amikacin. Profiling of 16S rRNA genes was used to track changes in faecal microbial community structure during this regimen in three patients.<br><br>RESULTS: The protocol was highly effective in treating UTI symptoms. None of the patients suffered a re-infection with C. difficile The faecal microbial communities remained undisturbed by treatment with intramuscular administration of gentamicin.<br><br>CONCLUSIONS: Despite falling out of favour in recent years, aminoglycoside antibiotics given parenterally have the advantage of minimal penetration into the gut lumen. A brief (3&#x2005;day) course of parenteral gentamicin was safe and effective in curing UTI in patients at high risk of C. difficile infection without perturbing their gut microbiota.}, }
@article {pmid27997976, year = {2016}, author = {Monsour, HP and Quigley, EM}, title = {The Microbiome: What Will the Future Hold?.}, journal = {Seminars in liver disease}, volume = {36}, number = {4}, pages = {354-359}, doi = {10.1055/s-0036-1594009}, pmid = {27997976}, issn = {1098-8971}, mesh = {Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation/trends ; Forecasting ; Gastrointestinal Tract/*microbiology ; Humans ; Liver Diseases/*microbiology ; Meta-Analysis as Topic ; *Microbiota ; Prebiotics ; Probiotics/therapeutic use ; Treatment Outcome ; }, abstract = {Current research on the human microbiome has opened our eyes to the intimate relationship that we have with the bacteria that populate our gastrointestinal tract and its potential relationship to health and disease. To date, clinical research on the microbiome has identified intriguing associations between an altered microbiome and disease states, but proven therapeutic applications have been very limited. The ingestion of prebiotics, probiotics, and/or synbiotics is appealing to the general public and has significant commercial value, but as yet, solid evidence for clinical efficacy in liver disease has been lacking due, in large part, to the paucity of high-quality clinical trials. On the other hand, the resounding success of fecal microbiota transplantation in Clostridium difficile infection has opened our eyes to the real potential of "pharmabiotics" and may well provide an intriguing template for the development of novel approaches to modulate the microbiome and its interactions with the host and thereby treat and/or prevent disease states. We will attempt to examine the current state of microbiome therapeutics and predict how these approaches might fit into the management of liver diseases in the future.}, }
@article {pmid27997974, year = {2016}, author = {Ali, AH and Carey, EJ and Lindor, KD}, title = {The Microbiome and Primary Sclerosing Cholangitis.}, journal = {Seminars in liver disease}, volume = {36}, number = {4}, pages = {340-348}, doi = {10.1055/s-0036-1594007}, pmid = {27997974}, issn = {1098-8971}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Cholangitis, Sclerosing/etiology/genetics/*therapy ; Disease Progression ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Liver/*microbiology ; Probiotics/therapeutic use ; Randomized Controlled Trials as Topic ; Sequence Analysis, RNA ; }, abstract = {Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with detrimental sequela. In many patients, PSC progresses to end-stage liver disease and hepatobiliary cancer. There is no medical therapy that is proven to halt or reverse the progression of PSC. Approximately 70 to 80% of PSC patients have inflammatory bowel disease, usually ulcerative colitis. The etiology of PSC is poorly understood. Several lines of evidence suggest that the intestinal microbiota plays an important role in the etiopathogenesis of PSC. Stemming from this theory, several antibiotics have been tried in PSC, some of which had shown promising results. Fecal microbiota transplantation is a novel therapy, and is currently being investigated as a potential therapeutic strategy in PSC along with probiotics. In this article, the authors discuss the current knowledge of the intestinal microbiota in PSC.}, }
@article {pmid27997854, year = {2017}, author = {Hryckowian, AJ and Pruss, KM and Sonnenburg, JL}, title = {The emerging metabolic view of Clostridium difficile pathogenesis.}, journal = {Current opinion in microbiology}, volume = {35}, number = {}, pages = {42-47}, pmid = {27997854}, issn = {1879-0364}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*pathogenicity/physiology ; Clostridium Infections/*microbiology/physiopathology/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; *Host-Pathogen Interactions ; Humans ; Inflammation ; Intestinal Diseases/metabolism/*microbiology ; Intestinal Mucosa/*metabolism ; Intestines/microbiology ; Mice ; }, abstract = {It is widely accepted that Clostridium difficile exploits dysbiosis and leverages inflammation to thrive in the gut environment, where it can asymptomatically colonize humans or cause a toxin-mediated disease ranging in severity from frequent watery diarrhea to pseudomembranous colitis or toxic megacolon. Here, we synthesize recent findings from the gut microbiota and enteric pathogenesis fields to inform the next steps toward a better understanding of C. difficile infection (CDI). In this review, we present a model in which the lifestyle of C. difficile is dictated by the metabolic state of the distal gut ecosystem. Contributions by C. difficile (specifically the production and action of the large glycosylating toxins TcdA and TcdB), the microbiota, and the host dictate whether the gut environment is supportive to the pathogen. Mechanistic, metabolic pathway-focused approaches encompassing the roles of all of these players are helping to elucidate the molecular ecology of the distal gut underlying a diseased or healthy ecosystem. A new generation of therapeutic strategies that are more targeted (and palatable) than fecal microbiota transplants or broad-spectrum antibiotics will be fueled by insight into the interspecies (host-microbe and microbe-microbe) interactions that differentiate healthy from pathogen-infested microbiotas.}, }
@article {pmid27995486, year = {2017}, author = {Tariq, R and Khanna, S}, title = {Clostridium difficile infection: Updates in management.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {36}, number = {1}, pages = {3-10}, pmid = {27995486}, issn = {0975-0711}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections ; Colitis/*microbiology/*therapy ; Diarrhea/*microbiology/*therapy ; Fecal Microbiota Transplantation ; Humans ; Immunotherapy ; Probiotics/therapeutic use ; Risk Factors ; Vaccination ; }, abstract = {Clostridium difficile was first identified in 1978 as a diarrhea-causing bacterium in humans. In the last three decades, C. difficile infection (CDI) has reached an epidemic state, both in health care and community settings worldwide. There has been substantial progress in the field of CDI, including identification of novel risk factors, presence of CDI in individuals not considered at risk previously, and treatment options including new drugs, monoclonal antibodies, and fecal microbiota transplantation. This review discusses epidemiology, novel and traditional risk factors, and updates in management for CDI.}, }
@article {pmid27989233, year = {2016}, author = {Klingensmith, NJ and Coopersmith, CM}, title = {Fecal microbiota transplantation for multiple organ dysfunction syndrome.}, journal = {Critical care (London, England)}, volume = {20}, number = {1}, pages = {398}, pmid = {27989233}, issn = {1466-609X}, support = {R01 GM113228/GM/NIGMS NIH HHS/United States ; R01 GM072808/GM/NIGMS NIH HHS/United States ; R01 GM104323/GM/NIGMS NIH HHS/United States ; T32 GM095442/GM/NIGMS NIH HHS/United States ; R01 GM109779/GM/NIGMS NIH HHS/United States ; }, mesh = {Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Intensive Care Units/organization &amp; administration ; Multiple Organ Failure/mortality/*therapy ; }, }
@article {pmid27984397, year = {2018}, author = {Tariq, R and Weatherly, R and Kammer, P and Pardi, DS and Khanna, S}, title = {Donor Screening Experience for Fecal Microbiota Transplantation in Patients With Recurrent C. difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {52}, number = {2}, pages = {146-150}, doi = {10.1097/MCG.0000000000000768}, pmid = {27984397}, issn = {1539-2031}, mesh = {Adult ; Aged ; Clostridium Infections/*therapy ; *Donor Selection ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Humans ; Male ; Middle Aged ; Practice Guidelines as Topic ; Recurrence ; Surveys and Questionnaires ; Young Adult ; }, abstract = {GOALS: To evaluate our experience with stool donor recruitment, screening, retention, and donor perception for fecal microbiota transplantation (FMT).<br><br>BACKGROUND: Multiply recurrent Clostridium difficile infection is being increasingly managed with FMT from donor stools. However, donor selection and recruitment is challenging due to lack of standard evidence-based guidelines, donor exclusion criteria, frequency of screening and donor commitment.<br><br>METHODS: Data on donors screened using institutional guidelines with history, blood and stool testing and their perspectives on donation were analyzed.<br><br>RESULTS: Overall 42 potential donors (21 known and 21 standard) were prescreened. Of known donors (median age 34 y, 66.6% female), none failed prescreening, blood or stool tests. Twelve standard donors (57%) failed prescreening based on history (depression, diarrhea, autoimmune disease, recent antibiotic exposure, colon polyps, pregnancy). Nine (median age 35 y, 44.4% female) passed blood and stool testing. On repeat screening, 3 were excluded (2-positive stool shiga toxin (asymptomatic), 1-pregnancy). One donor opted out and 5 became long-term donors; 3 have donated >50 times and 2 have donated >25 times. On the basis of donor perception questionnaire, most standard donors were aware of FMT for C. difficile infection as a treatment option and would not consider 3-monthly blood and stool testing inconvenient.<br><br>CONCLUSIONS: A significant proportion of healthy individuals who volunteered to become a standard donor failed prescreening and were not subjected to blood and stool testing. Repeat testing for asymptomatic donors may be a barrier to donor retention. Universal guidelines are needed to develop strategies to facilitate donor screening.}, }
@article {pmid27981821, year = {2017}, author = {Gaj, F and Biviano, I and Candeloro, L}, title = {Low energy manual anal stretch: an approach in the treatment of chronic anal fissure.}, journal = {Minerva chirurgica}, volume = {72}, number = {2}, pages = {103-107}, doi = {10.23736/S0026-4733.16.07156-X}, pmid = {27981821}, issn = {1827-1626}, mesh = {Adult ; Aged ; Chronic Disease ; Dilatation/adverse effects/*methods ; Fecal Incontinence/etiology/prevention &amp; control ; Female ; Fissure in Ano/*therapy ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Musculoskeletal Manipulations/adverse effects/*methods ; Prospective Studies ; Recurrence ; Treatment Outcome ; Visual Analog Scale ; Young Adult ; }, abstract = {BACKGROUND: Anal fissure is a tear in the epitelial lining of the anal canal. This is a very common anorectal disorder, but the choice of treatment is unclear. Sphincterotomy is effective but it is affected by a high risk of fecal incontinence. Manual anal stretch is aN efficacious, economic and safe maneuver. The aim of this prospective study was to assess the safety and effectiveness of anal stretch in resolving chronic anal fissures.<br><br>METHODS: Twenty-five patients with a clinical diagnosis of chronic anal fissure were submitted to anal stretch. All patients were submitted to anal stretch, after clinical evaluation. All patients were studied at basal time, and at 7 days, 3, 6 and 12 months after the treatment.<br><br>RESULTS: At 3 months and 6 months after the anal stretch, 88% and 94% of patients showed a resolution of anal fissures and only 12% have relapsed at 12 months, without complications, such as faecal incontinence.<br><br>CONCLUSIONS: The anal stretch appears to induce better resolution of chronic anal fissure with a very low risk of fecal incontinence.}, }
@article {pmid27981492, year = {2017}, author = {Klose, J and Tarantino, I and Kulu, Y and Bruckner, T and Trefz, S and Schmidt, T and Schneider, M and Hackert, T and Büchler, MW and Ulrich, A}, title = {Sphincter-Preserving Surgery for Low Rectal Cancer: Do We Overshoot the Mark?.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {21}, number = {5}, pages = {885-891}, pmid = {27981492}, issn = {1873-4626}, mesh = {Abdomen/surgery ; Adult ; Aged ; Aged, 80 and over ; Anal Canal/*surgery ; Digestive System Surgical Procedures/methods ; Fecal Incontinence/etiology ; Female ; Humans ; Male ; Middle Aged ; Quality of Life ; Recovery of Function ; Rectal Neoplasms/*surgery ; Rectum/*surgery ; }, abstract = {PURPOSE: Intersphincteric resection (ISR) is an alternative to abdominoperineal resection (APR) for a selected subset of patients with low rectal cancer, combining equivalent oncological outcome and sphincter preservation. However, functional results are heterogeneous and often imperfect. The aim of the present investigation was to determine the long-term functional results and quality of life after ISR.<br><br>METHODS: One hundred forty-three consecutive patients who underwent surgery for low rectal cancer were analysed. Sixty patients received ISR and 83 patients APR, respectively. Kaplan-Meier estimate was used to analyse patients' survival. The EORTC QLQ-C30, -C29 and the Wexner score were used to determine functional outcome and quality of life.<br><br>RESULTS: ISR and APR were both associated with comparable morbidity and no mortality. Patients' disease- and recurrence-free survival after ISR and APR were similar (p&#x2009;=&#x2009;0.2872 and p&#x2009;=&#x2009;0.4635). Closure of ileostomy was performed in 73% of all patients after ISR. Long-term outcome showed a rate of incontinence (Wexner score &#x2265;10) in 66% of the patients. Despite this, patients' quality of life was significantly better after ISR compared to APR in terms of abdominal complaints and psycho-emotional functioning.<br><br>CONCLUSIONS: ISR is technically feasible with acceptable postoperative morbidity rates. Functional results following ISR are compromised by incontinence as the most important complication. However, long-term quality of life is superior to APR, which should be considered when selecting patients for ISR.}, }
@article {pmid27979825, year = {2017}, author = {Zaborin, A and Krezalek, M and Hyoju, S and Defazio, JR and Setia, N and Belogortseva, N and Bindokas, VP and Guo, Q and Zaborina, O and Alverdy, JC}, title = {Critical role of microbiota within cecal crypts on the regenerative capacity of the intestinal epithelium following surgical stress.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {312}, number = {2}, pages = {G112-G122}, pmid = {27979825}, issn = {1522-1547}, support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cecum/*microbiology/ultrastructure ; Gene Expression Regulation ; Homeostasis ; Intestinal Mucosa/microbiology/*physiology/surgery ; Male ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Receptors, G-Protein-Coupled/genetics/metabolism ; }, abstract = {UNLABELLED: Cecal crypts represent a unique niche that are normally occupied by the commensal microbiota. Due to their density and close proximity to stem cells, microbiota within cecal crypts may modulate epithelial regeneration. Here we demonstrate that surgical stress, a process that invariably involves a short period of starvation, antibiotic exposure, and tissue injury, results in cecal crypt evacuation of their microbiota. Crypts devoid of their microbiota display pathophysiological features characterized by abnormal stem cell activation as judged by leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) staining, expansion of the proliferative zone toward the tips of the crypts, and an increase in apoptosis. In addition, crypts devoid of their microbiota display loss of their regenerative capacity as assessed by their ability to form organoids ex vivo. When a four-member human pathogen community isolated from the stool of a critically ill patient is introduced into the cecum of mice with empty crypts, crypts become occupied by the pathogens and further disruption of crypt homeostasis is observed. Fecal microbiota transplantation restores the cecal crypts' microbiota, normalizes homeostasis within crypts, and reestablishes crypt regenerative capacity. Taken together, these findings define an emerging role for the microbiota within cecal crypts to maintain epithelial cell homeostasis in a manner that may enhance recovery in response to the physiological stress imposed by the process of surgery.<br><br>NEW &amp; NOTEWORTHY: This study provides novel insight into the process by which surgical injury places the intestinal epithelium at risk for colonization by pathogenic microbes and impairment of its regenerative capacity via loss of its microbiota. We show that fecal transplant restores crypt homeostasis in association with repopulation of the microbiota within cecal crypts.}, }
@article {pmid27978522, year = {2017}, author = {Konturek, PC and Haziri, D and Helfritzsch, H and Hess, T and Harsch, IA}, title = {Successful Therapy of Severe Pseudomembranous Clostridium difficile Colitis Using a Combination of Fecal Microbiota Therapy and Fidaxomicin.}, journal = {Medical principles and practice : international journal of the Kuwait University, Health Science Centre}, volume = {26}, number = {2}, pages = {182-184}, pmid = {27978522}, issn = {1423-0151}, mesh = {Aged ; Aminoglycosides/*therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile ; Clostridium Infections/*therapy ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Fidaxomicin ; Humans ; }, abstract = {OBJECTIVE: The aim of this work was to describe the use of a combination of fidaxomicin and fecal microbiota therapy (FMT) in Clostridium difficile infection (CDI).<br><br>A 78-year-old female, who was admitted for surgery due to acute diverticulitis caused by postoperative complications and broad antibiotic therapy, developed CDI-induced colitis. Despite the introduction of metronidazole and vancomycin therapy, her clinical condition continued to deteriorate. She was transferred to the intensive care unit where FMT followed by fidaxomicin were performed because her C-reactive protein and leucocyte levels remained elevated. Further clinical improvement and the resolution of colitis was observed.<br><br>CONCLUSION: In this case, severe CDI colitis was successfully treated with the combination of FMT and fidaxomicin.}, }
@article {pmid27974040, year = {2016}, author = {Lynch, SV and Pedersen, O}, title = {The Human Intestinal Microbiome in Health and Disease.}, journal = {The New England journal of medicine}, volume = {375}, number = {24}, pages = {2369-2379}, doi = {10.1056/NEJMra1600266}, pmid = {27974040}, issn = {1533-4406}, mesh = {Aging/physiology ; Animals ; *Biological Therapy ; Diet ; Disease/*etiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Health ; Humans ; }, }
@article {pmid27965663, year = {2016}, author = {Khan, N and Vidyarthi, A and Nadeem, S and Negi, S and Nair, G and Agrewala, JN}, title = {Alteration in the Gut Microbiota Provokes Susceptibility to Tuberculosis.}, journal = {Frontiers in immunology}, volume = {7}, number = {}, pages = {529}, pmid = {27965663}, issn = {1664-3224}, abstract = {The microbiota that resides in the gastrointestinal tract provides essential health benefits to the host. In particular, they regulate immune homeostasis. Recently, several evidences indicate that alteration in the gut microbial community can cause infectious and non-infectious diseases. Tuberculosis (TB) is the most devastating disease, inflicting mortality and morbidity. It remains unexplored, whether changes in the gut microbiota can provoke or prevent TB. In the current study, we have demonstrated the antibiotics driven changes in the gut microbial composition and their impact on the survival of Mycobacterium tuberculosis (Mtb) in the lungs, liver, and spleen of infected mice, compared to those with intact microbiota. Interestingly, dysbiosis of microbes showed significant increase in the bacterial burden in lungs and dissemination of Mtb to spleen and liver. Furthermore, elevation in the number of Tregs and decline in the pool of IFN-γ- and TNF-α-releasing CD4 T cells was noticed. Interestingly, fecal transplantation in the gut microbiota disrupted animals exhibited improved Th1 immunity and lesser Tregs population. Importantly, these animals displayed reduced severity to Mtb infection. This study for the first time demonstrated the novel role of gut microbes in the susceptibility to TB and its prevention by microbial implants. In future, microbial therapies may help in treating patients suffering from TB.}, }
@article {pmid27959316, year = {2016}, author = {Liubakka, A and Vaughn, BP}, title = {Clostridium difficile Infection and Fecal Microbiota Transplant.}, journal = {AACN advanced critical care}, volume = {27}, number = {3}, pages = {324-337}, pmid = {27959316}, issn = {1559-7776}, support = {L30 DK099831/DK/NIDDK NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*growth &amp; development ; Clostridium Infections/*diagnosis/drug therapy/epidemiology/*therapy ; Education, Medical, Continuing ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; Middle Aged ; Risk Factors ; Treatment Outcome ; United States ; }, abstract = {Clostridium difficile infection (CDI) is a major source of morbidity and mortality for hospitalized patients. Although most patients have a clinical response to existing antimicrobial therapies, recurrent infection develops in up to 30% of patients. Fecal microbiota transplant is a novel approach to this complex problem, with an efficacy rate of nearly 90% in the setting of multiple recurrent CDI. This review covers the current epidemiology of CDI (including toxigenic and nontoxigenic strains, risk factors for infection, and recurrent infection), methods of diagnosis, existing first-line therapies in CDI, the role of fecal microbiota transplant for multiple recurrent CDIs, and the potential use of fecal microbial transplant for patients with severe or refractory infection.}, }
@article {pmid27943520, year = {2017}, author = {Khafagy, WW and El-Said, MM and Thabet, WM and Aref, SE and Omar, W and Emile, SH and Elfeki, H and El-Ghonemy, MS and El-Shobaky, MT}, title = {Evaluation of anatomical and functional results of overlapping anal sphincter repair with or without the injection of bone marrow aspirate concentrate: a case-control study.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {19}, number = {1}, pages = {O66-O74}, doi = {10.1111/codi.13579}, pmid = {27943520}, issn = {1463-1318}, mesh = {Adult ; Anal Canal/diagnostic imaging/*surgery ; Bone Marrow/*surgery ; Bone Marrow Transplantation/*methods ; Case-Control Studies ; Digestive System Surgical Procedures/*methods ; Endosonography/methods ; Fecal Incontinence/diagnostic imaging/*surgery ; Female ; Follow-Up Studies ; Humans ; Injections/methods ; Male ; Middle Aged ; Prospective Studies ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {AIM: Overlapping anal sphincter repair (OASR) is used for treatment of faecal incontinence due to an external anal sphincter (EAS) defect; however, it is not the optimal treatment as its functional results tend to deteriorate significantly with time. The present study aimed to evaluate the effect of local injection of bone marrow aspirate concentrate (BMAC) on the outcome of OASR.<br><br>METHOD: We compared a prospective group of 20 patients with EAS defect who were managed with OASR and BMAC injection (group I) with a historical control group of an equal number of patients managed with OASR alone (group II). Patients were assessed preoperatively and during follow-up by the Wexner continence score and endoanal ultrasound. The primary end-points were the improvement of the continence level measured by the Wexner score and the residual EAS defect size measured by endoanal ultrasound.<br><br>RESULTS: At the end of follow-up, group I had significantly lower mean postoperative Wexner score (5.4&#xa0;&#xb1;&#xa0;7.6 vs 10.6&#xa0;&#xb1;&#xa0;7.4; P&#xa0;=&#xa0;0.03) and smaller EAS defect percentage (12.2&#xa0;&#xb1;&#xa0;17.5 vs 18.3&#xa0;&#xb1;&#xa0;18.9). These findings were statistically significant in patients with a small preoperative EAS defect equal to or less than one-third of the anal circumference. Patients with larger preoperative EAS did not show a significant improvement of the continence level after repair in either group.<br><br>CONCLUSION: Augmenting OASR with local injection of BMAC in patients with faecal incontinence caused by an EAS defect, particularly a smaller defect, can improve both functional and anatomical outcomes of OASR.}, }
@article {pmid27935413, year = {2017}, author = {Broecker, F and Russo, G and Klumpp, J and Moelling, K}, title = {Stable core virome despite variable microbiome after fecal transfer.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {214-220}, pmid = {27935413}, issn = {1949-0984}, mesh = {Clostridium Infections/*therapy ; Dysbiosis ; *Fecal Microbiota Transplantation ; Feces/*microbiology/*virology ; Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; RNA, Ribosomal, 16S/isolation &amp; purification ; Viruses/*isolation &amp; purification ; }, abstract = {We recently described the 4.5-year time course of the enteric bacterial microbiota and virome of a patient cured from recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT). Here, we extended the virome analyses and found the patient's phage population to exhibit highly donor-similar characteristics following FMT, which remained stable for the whole period tested (up to 7 months). Moreover, the detected viral populations of donor and patient exhibited comparable diversity and richness. These findings were unexpected since enteric viromes are normally highly variable, assumed to influence the bacterial host community and change with environmental conditions. In contrast to the virome, the bacterial microbiota varied indeed for more than 7 months with ongoing dysbiosis before it reached donor similarity. Our findings that are based on sequence information and protein domain analysis seem to suggest that stable phage properties correlate with successful FMT better than the changing bacterial communities. We speculate that we here preferentially detected a stable core virome, which dominated over a variable flexible virome that may have been too heterogeneous for experimental detection or was underrepresented in the databases. It will be interesting to analyze whether the enteric virome allows predictions for the clinical outcome of FMT for rCDI and other diseases such as inflammatory bowel disease or obesity.}, }
@article {pmid27934806, year = {2016}, author = {Yadav, P and Khalil, S and Mirdha, BR}, title = {Molecular appraisal of intestinal parasitic infection in transplant recipients.}, journal = {The Indian journal of medical research}, volume = {144}, number = {2}, pages = {258-263}, pmid = {27934806}, issn = {0971-5916}, mesh = {Adult ; Bone Marrow Transplantation/adverse effects ; Child ; Cryptosporidium/*genetics/isolation &amp; purification ; Diarrhea/genetics/*parasitology ; Feces/*parasitology ; Female ; Genotype ; Giardia lamblia/*genetics/isolation &amp; purification ; Humans ; Intestinal Diseases, Parasitic/genetics/*parasitology/transmission ; Kidney Transplantation/adverse effects ; Liver Transplantation/adverse effects ; Male ; Middle Aged ; Protozoan Proteins/genetics/isolation &amp; purification ; Transplant Recipients ; Triose-Phosphate Isomerase/genetics/isolation &amp; purification ; }, abstract = {BACKGROUND &amp; OBJECTIVES: Diarrhoea is the main clinical manifestation caused by intestinal parasitic infections in patients, with special reference to transplant recipients who require careful consideration to reduce morbidity and mortality. Further, molecular characterization of some important parasites is necessary to delineate the different modes of transmission to consider appropriate management strategies. We undertook this study to investigate the intestinal parasitic infections in transplant recipients with or without diarrhoea, and the genotypes of the isolated parasites were also determined.<br><br>METHODS: Stool samples from 38 transplant recipients comprising 29 post-renal, two liver and seven bone marrow transplant (BMT) recipients presenting with diarrhoea and 50 transplant recipients (42 post-renal transplant, eight BMT) without diarrhoea were examined for the presence of intestinal parasites by light microscopy using wet mount, modified Ziehl-Neelsen staining for intestinal coccidia and modified trichrome staining for microsporidia. Genotypes of Cryptosporidium species were determined by multilocus genotyping using small subunit ribosomal (SSUrRNA), Cryptosporidium oocyst wall protein (COWP) and dihydrofolate reductase (DHFR) as the target genes. Assemblage study for Giardia lamblia was performed using triose phosphate isomerase (TPI) as the target gene. Samples were also screened for bacterial, fungal and viral pathogens.<br><br>RESULTS: The parasites that were detected included Cryptosporidium species (21%, 8/38), Cystoisospora (Isospora) belli (8%, 3), Cyclospora cayetanensis (5%, 2), G. lamblia (11%, 4), Hymenolepis nana (11%, 4), Strongyloides stercoralis (3%, 1) and Blastocystis hominis (3%, 1). Multilocus genotyping of Cryptosporidium species at SSUrRNA, COWP and DHFR loci could detect four isolates of C. hominis; two of C. parvum, one of mixed genotype and one could not be genotyped. All the C. hominis isolates were detected in adult post-renal transplant (PRT) recipients, whereas the C. parvum isolates included a child with BMT and an adult with PRT. Clostridium difficle, cytomegalovirus and Candida albicans were found in 2, 3 and 2 patients, respectively.<br><br>In the present study, C. hominis was observed as an important parasite causing intestinal infections in transplant recipients. Multilocus genotyping of Cryptosporidium species could detect four isolates of C. hominis; two of C. parvum, one of mixed genotype and one could not be genotyped. Genotyping of G. lamblia revealed that assemblage B was most common.}, }
@article {pmid27929078, year = {2016}, author = {Lin, YW and Montassier, E and Knights, D and Wei, LN}, title = {Gut microbiota from metabolic disease-resistant, macrophage-specific RIP140 knockdown mice improves metabolic phenotype and gastrointestinal integrity.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {38599}, pmid = {27929078}, issn = {2045-2322}, support = {R01 DK054733/DK/NIDDK NIH HHS/United States ; R01 DK060521/DK/NIDDK NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/*genetics ; Animals ; Diet/adverse effects ; *Disease Resistance ; Energy Metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Genetic Association Studies ; Genotype ; Macrophages/*metabolism ; Male ; Metabolic Diseases/diagnosis/*etiology/*metabolism/therapy ; Mice ; Mice, Knockout ; Nuclear Proteins/*genetics ; Nuclear Receptor Interacting Protein 1 ; *Phenotype ; }, abstract = {While fecal microbiota transplantation (FMT) presents an attractive therapeutic strategy, it remains unclear how to choose the microbiota repertoire that most effectively transfers benefit to recipients. We identified a beneficial taxonomic repertoire in a transgenic mouse model (RIP140mϕKD) which resists the development of high fat diet (HFD)-induced metabolic diseases due to enhanced anti-inflammation engineered by lowering receptor interacting protein (RIP140) expression in macrophage. We confirmed using FMT from HFD-fed RIP140mϕKD to wild type (WT) mice that recipient mice acquired the microbiota repertoire of donor mice. Importantly, FMT from RIP140mϕKD to WT not only effectively transferred the beneficial taxonomic repertoire to WT recipients, but also enabled recipient animals acquiring the anti-inflammatory status of RIP140mϕKD donor animals and avoid HFD-induced insulin resistance, which is associated with significantly improved intestinal integrity. We conclude that FMT can transfer not only microbiota but also the donors' intestinal innate immune status and improved intestinal integrity.}, }
@article {pmid27927779, year = {2017}, author = {Emal, D and Rampanelli, E and Stroo, I and Butter, LM and Teske, GJ and Claessen, N and Stokman, G and Florquin, S and Leemans, JC and Dessing, MC}, title = {Depletion of Gut Microbiota Protects against Renal Ischemia-Reperfusion Injury.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {28}, number = {5}, pages = {1450-1461}, pmid = {27927779}, issn = {1533-3450}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology/*therapeutic use ; CX3C Chemokine Receptor 1 ; Epidermal Growth Factor/physiology ; Gastrointestinal Microbiome/*drug effects ; Kidney/*blood supply ; Macrophages/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Chemokine/physiology ; Reperfusion Injury/*microbiology/*prevention &amp; control ; }, abstract = {An accumulating body of evidence shows that gut microbiota fulfill an important role in health and disease by modulating local and systemic immunity. The importance of the microbiome in the development of kidney disease, however, is largely unknown. To study this concept, we depleted gut microbiota with broad-spectrum antibiotics and performed renal ischemia-reperfusion (I/R) injury in mice. Depletion of the microbiota significantly attenuated renal damage, dysfunction, and remote organ injury and maintained tubular integrity after renal I/R injury. Gut flora-depleted mice expressed lower levels of F4/80 and chemokine receptors CX3CR1 and CCR2 in the F4/80[+] renal resident macrophage population and bone marrow (BM) monocytes than did control mice. Additionally, compared with control BM monocytes, BM monocytes from gut flora-depleted mice had decreased migratory capacity toward CX3CL1 and CCL2 ligands. To study whether these effects were driven by depletion of the microbiota, we performed fecal transplants in antibiotic-treated mice and found that transplant of fecal material from an untreated mouse abolished the protective effect of microbiota depletion upon renal I/R injury. In conclusion, we show that depletion of gut microbiota profoundly protects against renal I/R injury by reducing maturation status of F4/80[+] renal resident macrophages and BM monocytes. Therefore, dampening the inflammatory response by targeting microbiota-derived mediators might be a promising therapy against I/R injury.}, }
@article {pmid27923723, year = {2017}, author = {Chin, SM and Sauk, J and Mahabamunuge, J and Kaplan, JL and Hohmann, EL and Khalili, H}, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in Patients With Inflammatory Bowel Disease: A Single-Center Experience.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {15}, number = {4}, pages = {597-599}, pmid = {27923723}, issn = {1542-7714}, support = {K23 DK099681/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Child ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Humans ; Inflammatory Bowel Diseases/*complications ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Treatment Outcome ; Young Adult ; }, }
@article {pmid27922565, year = {2017}, author = {Aroniadis, OC and Drossman, DA and Simrén, M}, title = {A Perspective on Brain-Gut Communication: The American Gastroenterology Association and American Psychosomatic Society Joint Symposium on Brain-Gut Interactions and the Intestinal Microenvironment.}, journal = {Psychosomatic medicine}, volume = {79}, number = {8}, pages = {847-856}, doi = {10.1097/PSY.0000000000000431}, pmid = {27922565}, issn = {1534-7796}, mesh = {*Brain ; *Congresses as Topic ; *Gastroenterology ; *Gastrointestinal Microbiome ; Humans ; *Psychosomatic Medicine ; *Societies, Medical ; United States ; }, abstract = {BACKGROUND: Alterations in brain-gut communication and the intestinal microenvironment have been implicated in a variety of medical and neuropsychiatric diseases. Three central areas require basic and clinical research: (1) how the intestinal microenvironment interacts with the host immune system, central nervous system, and enteric nervous system; (2) the role of the intestinal microenvironment in the pathogenesis of medical and neuropsychiatric disease; and (3) the effects of diet, prebiotics, probiotics, and fecal microbiota transplantation on the intestinal microenvironment and the treatment of disease.<br><br>METHODS: This review article is based on a symposium convened by the American Gastroenterology Association and the American Psychosomatic Society to foster interest in the role of the intestinal microenvironment in brain-gut communication and pathogenesis of neuropsychiatric and biopsychosocial disorders. The aims were to define the state of the art of the current scientific knowledge base and to identify guidelines and future directions for new research in this area.<br><br>RESULTS: This review provides a characterization of the intestinal microbial composition and function. We also provide evidence for the interactions between the intestinal microbiome, the host, and the environment. The role of the intestinal microbiome in medical and neuropsychiatric diseases is reviewed as well as the treatment effects of manipulation of the intestinal microbiome.<br><br>CONCLUSIONS: Based on this review, opportunities and challenges for conducting research in the field are described, leading to potential avenues for future research.}, }
@article {pmid27917075, year = {2016}, author = {Al-Jashaami, LS and DuPont, HL}, title = {Management of Clostridium difficile Infection.}, journal = {Gastroenterology &amp; hepatology}, volume = {12}, number = {10}, pages = {609-616}, pmid = {27917075}, issn = {1554-7914}, abstract = {Since the discovery of Clostridium difficile infection (CDI) in the 1970s, there has been an increase in the incidence, severity, and recurrence rate of the disease. We reviewed the recent CDI literature in PubMed published before February 28, 2016 that focused on advances in therapy. Despite a large number of studies describing methods for diagnosing the disease, there is currently no definitive test that identifies this infection with certainty, which complicates therapy. Recommended therapy for CDI includes oral metronidazole for mild cases and oral vancomycin or fidaxomicin for moderate to severe cases, each given for 10 to 14 days. For infection with spore-forming C difficile, this length of treatment may be insufficient to lead to cure; however, continuing antibiotics for longer periods of time may unfavorably alter the microbiome, preventing recovery. Treatment with metronidazole has been associated with an increasing failure rate, and the only clear recommended form of metronidazole for treatment of CDI is the intravenous formulation for patients unable to take oral medications. For vancomycin or fidaxomicin treatment of first CDI recurrences, the drug used in the initial bout can be repeated. For second or future recurrences, vancomycin can be given in pulsed or tapered doses. New modalities of treatment, such as bacteriotherapy and immunotherapy, show promise for the treatment of recurrent CDI.}, }
@article {pmid27912759, year = {2016}, author = {Raghunathan, VM and Sheng, I and Lim, SH}, title = {Intestinal dysbiosis and allogeneic hematopoietic progenitor cell transplantation.}, journal = {Journal of translational medicine}, volume = {14}, number = {1}, pages = {335}, pmid = {27912759}, issn = {1479-5876}, mesh = {Dysbiosis/*pathology ; Graft vs Host Disease/etiology/microbiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Intestines/*microbiology ; Transplantation, Homologous/adverse effects ; }, abstract = {The intestinal microbiota is a diverse and dynamic ecosystem that is increasingly understood to play a vital role in human health. Hematopoietic stem cell transplant recipients undergo prolonged exposure to antimicrobials, chemotherapeutic agents, and immunosuppressants, resulting in profound shifts in the gut microbiome. A growing body of research has revealed the ways in which these microbiologic shifts shape immune modulation, affecting susceptibility to infections and graft-versus-host disease, the two major post-transplant complications in this population. As transplant medicine becomes increasingly personalized, the potential for microbiome-modulating treatments holds immense potential. Strategies to preserve the intestinal microbiota, including targeted antibiotics, prebiotics and probiotics, and fecal microbiota transplant could mitigate some of the microbiologic shifts in stem cell transplant recipients, and reduce the incidence of peri-transplant morbidity and mortality.}, }
@article {pmid27908697, year = {2017}, author = {Burke, DG and Harrison, MJ and Fleming, C and McCarthy, M and Shortt, C and Sulaiman, I and Murphy, DM and Eustace, JA and Shanahan, F and Hill, C and Stanton, C and Rea, MC and Ross, RP and Plant, BJ}, title = {Clostridium difficile carriage in adult cystic fibrosis (CF); implications for patients with CF and the potential for transmission of nosocomial infection.}, journal = {Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society}, volume = {16}, number = {2}, pages = {291-298}, doi = {10.1016/j.jcf.2016.09.008}, pmid = {27908697}, issn = {1873-5010}, mesh = {Adult ; Bacterial Typing Techniques/methods ; *Carrier State/diagnosis/epidemiology ; Clostridioides difficile/*isolation &amp; purification ; Cohort Studies ; *Cross Infection/diagnosis/microbiology ; *Cystic Fibrosis/epidemiology/microbiology ; *Enterocolitis, Pseudomembranous/diagnosis/epidemiology ; Female ; Humans ; Ireland/epidemiology ; Male ; Microbial Sensitivity Tests/methods ; Prevalence ; }, abstract = {Clostridium difficile is an anaerobic Gram-positive, spore-forming, toxin-producing bacillus transmitted among humans through the faecal-oral route. Despite increasing carriage rates and the presence of C. difficile toxin in stool, patients with CF rarely appear to develop typical manifestations of C. difficile infection (CDI). In this study, we examined the carriage, toxin production, ribotype distribution and antibiotic susceptibility of C. difficile in a cohort of 60 adult patients with CF who were pre-lung transplant. C. difficile was detected in 50% (30/60) of patients with CF by culturing for the bacteria. C. difficile toxin was detected in 63% (19/30) of C. difficile-positive stool samples. All toxin-positive stool samples contained toxigenic C. difficile strains harbouring toxin genes, tcdA and tcdB. Despite the presence of C. difficile and its toxin in patient stool, no acute gastrointestinal symptoms were reported. Ribotyping of C. difficile strains revealed 16 distinct ribotypes (RT), 11 of which are known to be disease-causing including the hyper-virulent RT078. Additionally, strains RT002, RT014, and RT015, which are common in non-CF nosocomial infection were described. All strains were susceptible to vancomycin, metronidazole, fusidic acid and rifampicin. No correlation was observed between carriage of C. difficile or any characteristics of isolated strains and any recorded clinical parameters or treatment received. We demonstrate a high prevalence of hypervirulent, toxigenic strains of C. difficile in asymptomatic patients with CF. This highlights the potential role of asymptomatic patients with CF in nosocomial transmission of C. difficile.}, }
@article {pmid27903747, year = {2017}, author = {Sung, MM and Kim, TT and Denou, E and Soltys, CM and Hamza, SM and Byrne, NJ and Masson, G and Park, H and Wishart, DS and Madsen, KL and Schertzer, JD and Dyck, JR}, title = {Improved Glucose Homeostasis in Obese Mice Treated With Resveratrol Is Associated With Alterations in the Gut Microbiome.}, journal = {Diabetes}, volume = {66}, number = {2}, pages = {418-425}, doi = {10.2337/db16-0680}, pmid = {27903747}, issn = {1939-327X}, mesh = {Animals ; Bacteroides ; Blood Glucose/*drug effects/metabolism ; Chromatography, Liquid ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects/genetics ; Glucose/metabolism ; Glucose Tolerance Test ; Homeostasis/drug effects ; Male ; Mice ; Mice, Obese ; Obesity/*metabolism/microbiology ; Resveratrol ; Stilbenes/*pharmacology ; Tandem Mass Spectrometry ; }, abstract = {Oral administration of resveratrol is able to improve glucose homeostasis in obese individuals. Herein we show that resveratrol ingestion produces taxonomic and predicted functional changes in the gut microbiome of obese mice. In particular, changes in the gut microbiome were characterized by a decreased relative abundance of Turicibacteraceae, Moryella, Lachnospiraceae, and Akkermansia and an increased relative abundance of Bacteroides and Parabacteroides Moreover, fecal transplantation from healthy resveratrol-fed donor mice is sufficient to improve glucose homeostasis in obese mice, suggesting that the resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol.}, }
@article {pmid27893543, year = {2017}, author = {Ishikawa, D and Sasaki, T and Osada, T and Kuwahara-Arai, K and Haga, K and Shibuya, T and Hiramatsu, K and Watanabe, S}, title = {Changes in Intestinal Microbiota Following Combination Therapy with Fecal Microbial Transplantation and Antibiotics for Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {23}, number = {1}, pages = {116-125}, doi = {10.1097/MIB.0000000000000975}, pmid = {27893543}, issn = {1536-4844}, mesh = {Adult ; Aged ; Amoxicillin/administration &amp; dosage ; Anti-Bacterial Agents/*administration &amp; dosage ; Colitis, Ulcerative/complications/microbiology/*therapy ; Colon/microbiology ; Colonoscopy/methods ; Combined Modality Therapy ; Drug Therapy, Combination ; Dysbiosis/etiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Fosfomycin/administration &amp; dosage ; *Gastrointestinal Microbiome ; Humans ; Male ; Metronidazole/administration &amp; dosage ; Middle Aged ; Pilot Projects ; Prospective Studies ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a potential therapeutic approach to restore normal intestinal microbiota in patients with ulcerative colitis (UC), which is associated with dysbiosis; however, treatment efficacy remains unclear. Hence, we studied the impact of antibiotic pretreatment with amoxicillin, fosfomycin, and metronidazole (AFM therapy) and FMT versus AFM alone.<br><br>METHODS: AFM therapy was administered to patients for 2 weeks until 2 days before FMT. Patients' spouses or relatives were selected as donor candidates. Donor fecal samples were collected on the day of administration and transferred into the patient's colon by colonoscopy within 6 hours. Microbiome analysis was performed by 16S rRNA next-generation sequencing.<br><br>RESULTS: Patients with mild-to-severe active UC (combination-therapy group, n = 21; AFM monotherapy group, n = 20) were included. Thirty-six patients completed this assessment (combination-therapy group, n = 17; AFM monotherapy group, n = 19). A higher clinical response was observed after combination therapy compared with AFM monotherapy at 4 weeks after treatment. After the 2-week AFM therapy, the Bacteroidetes composition was nearly abolished. The Bacteroidetes proportion recovered in clinical responders at 4 weeks after FMT was not observed in the AFM monotherapy group. Persistent antimicrobial-associated dysbiosis found in the AFM monotherapy group was reversed by FMT. The recovery rate of Bacteroidetes at 4 weeks after FMT correlated with endoscopic severity.<br><br>CONCLUSIONS: FMT following antimicrobial bowel cleansing synergistically contributes to the recovery of the Bacteroidetes composition, which is associated with clinical response and UC severity. Thus, this therapeutic protocol may be useful for managing UC.}, }
@article {pmid27891639, year = {2017}, author = {König, J and Siebenhaar, A and Högenauer, C and Arkkila, P and Nieuwdorp, M and Norén, T and Ponsioen, CY and Rosien, U and Rossen, NG and Satokari, R and Stallmach, A and de Vos, W and Keller, J and Brummer, RJ}, title = {Consensus report: faecal microbiota transfer - clinical applications and procedures.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {45}, number = {2}, pages = {222-239}, pmid = {27891639}, issn = {1365-2036}, mesh = {Animals ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*therapy ; Irritable Bowel Syndrome/*therapy ; Metabolic Syndrome/*therapy ; }, abstract = {BACKGROUND: Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication.<br><br>AIM: To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT.<br><br>METHODS: Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors.<br><br>RESULTS: Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings.<br><br>CONCLUSIONS: Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.}, }
@article {pmid27890791, year = {2017}, author = {Ferrere, G and Wrzosek, L and Cailleux, F and Turpin, W and Puchois, V and Spatz, M and Ciocan, D and Rainteau, D and Humbert, L and Hugot, C and Gaudin, F and Noordine, ML and Robert, V and Berrebi, D and Thomas, M and Naveau, S and Perlemuter, G and Cassard, AM}, title = {Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury in mice.}, journal = {Journal of hepatology}, volume = {66}, number = {4}, pages = {806-815}, doi = {10.1016/j.jhep.2016.11.008}, pmid = {27890791}, issn = {1600-0641}, mesh = {Animals ; Bacteroides/genetics/isolation &amp; purification/physiology ; Bile Acids and Salts/metabolism ; Dietary Fiber/administration &amp; dosage ; Disease Models, Animal ; Disease Susceptibility/microbiology ; Dysbiosis/*microbiology/*prevention &amp; control ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Liver Diseases, Alcoholic/*microbiology/*prevention &amp; control ; Mice ; Mice, Inbred C57BL ; Pectins/administration &amp; dosage ; Prebiotics/administration &amp; dosage ; }, abstract = {BACKGROUND &amp; AIMS: Alcoholic liver disease (ALD) is a leading cause of liver failure and mortality. In humans, severe alcoholic hepatitis is associated with key changes to intestinal microbiota (IM), which influences individual sensitivity to develop advanced ALD. We used the different susceptibility to ALD observed in two distinct animal facilities to test the efficiency of two complementary strategies (fecal microbiota transplantation and prebiotic treatment) to reverse dysbiosis and prevent ALD.<br><br>METHODS: Mice were fed alcohol in two distinct animal facilities with a Lieber DeCarli diet. Fecal microbiota transplantation was performed with fresh feces from alcohol-resistant donor mice to alcohol-sensitive receiver mice three times a week. Another group of mice received pectin during the entire alcohol consumption period.<br><br>RESULTS: Ethanol induced steatosis and liver inflammation, which were associated with disruption of gut homeostasis, in alcohol-sensitive, but not alcohol resistant mice. IM analysis showed that the proportion of Bacteroides was specifically lower in alcohol-sensitive mice (p<0.05). Principal coordinate analysis showed that the IM of sensitive and resistant mice clustered differently. We targeted IM using two different strategies to prevent alcohol-induced liver lesions: (1) pectin treatment which induced major modifications of the IM, (2) fecal microbiota transplantation which resulted in an IM very close to that of resistant donor mice in the sensitive recipient mice. Both methods prevented steatosis, liver inflammation, and restored gut homeostasis.<br><br>CONCLUSIONS: Manipulation of IM can prevent alcohol-induced liver injury. The IM should be considered as a new therapeutic target in ALD.<br><br>LAY SUMMARY: Sensitivity to alcoholic liver disease (ALD) is driven by intestinal microbiota in alcohol fed mice. Treatment of mice with alcohol-induced liver lesions by fecal transplant from alcohol fed mice resistant to ALD or with prebiotic (pectin) prevents ALD. These findings open new possibilities for treatment of human ALD through intestinal microbiota manipulation.}, }
@article {pmid27890428, year = {2017}, author = {Ford, CD and Gazdik, MA and Lopansri, BK and Webb, B and Mitchell, B and Coombs, J and Hoda, D and Petersen, FB}, title = {Vancomycin-Resistant Enterococcus Colonization and Bacteremia and Hematopoietic Stem Cell Transplantation Outcomes.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {23}, number = {2}, pages = {340-346}, doi = {10.1016/j.bbmt.2016.11.017}, pmid = {27890428}, issn = {1523-6536}, mesh = {Adolescent ; Adult ; Aged ; Antibiotic Prophylaxis ; Bacteremia/drug therapy/etiology/*microbiology ; Comorbidity ; Costs and Cost Analysis ; Enterococcus/drug effects/*isolation &amp; purification ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome ; Graft vs Host Disease/etiology ; Gram-Positive Bacterial Infections/drug therapy/economics/etiology/*microbiology ; *Hematopoietic Stem Cell Transplantation/adverse effects/economics/mortality ; Humans ; Immunocompromised Host ; Leukemia/therapy ; Male ; Middle Aged ; Treatment Outcome ; *Vancomycin Resistance ; Young Adult ; }, abstract = {The association between pre-hematopoietic stem cell transplantation (HSCT) vancomycin-resistant Enterococcus (VRE) colonization, HSCT-associated VRE bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of whom 109 also received leukemia induction/consolidation on our unit. All inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not associated with increases in HSCT mortality but did identify a subgroup of HSCT recipients with a higher risk for VRE bacteremia and possibly bacteremia from other organisms. The major risk factor for pre-HSCT colonization was the number of hospital inpatient days between initial admission for leukemia and HSCT. One-third of evaluable patients colonized before HSCT were VRE-culture negative on admission for HSCT; these patients had an increased risk for subsequent VRE stool surveillance positivity but not VRE bacteremia. Molecular typing of VRE isolates obtained before and after HSCT showed that VRE strains frequently change. Postengraftment VRE bacteremia was associated with a much higher mortality than pre-engraftment VRE bacteremia. Pre-engraftment bacteremia from any organism was associated with an alternative donor and resulted in an increase in hospital length of stay and cost. Mortality was similar for pre-engraftment VRE bacteremia and pre-engraftment bacteremia due to other organisms, but mortality associated with post-engraftment VRE bacteremia was higher and largely explained by associated severe graft-versus-host disease and relapsed leukemia. These data emphasize the importance of distinguishing between VRE colonization before HSCT and at HSCT, between pre-engraftment and postengraftment VRE bacteremia, and between VRE bacteremia and bacteremia from other organisms.}, }
@article {pmid27888860, year = {2016}, author = {Chaparro, M}, title = {Treatment of inflammatory bowel disease: what's new in Digestive Disease Week 2016.}, journal = {Gastroenterologia y hepatologia}, volume = {39 Suppl 1}, number = {}, pages = {20-28}, doi = {10.1016/S0210-5705(16)30171-6}, pmid = {27888860}, issn = {0210-5705}, mesh = {Humans ; Inflammatory Bowel Diseases/*therapy ; }, abstract = {Inflammatory bowel disease is a chronic disorder of unknown aetiology that results from a pathologic response from both the innate and acquired immune systems, leading to chronic inflammation of the gastrointestinal tract. New drugs have been introduced into the therapeutic armamentarium of inflammatory bowel disease but are not effective in all patients; moreover, among initial responders, there have been reports of loss of response over time. In addition, these drugs sometimes have adverse effects and are often expensive. The present article reviews the studies presented at Digestive Disease Week 2016 that provided new data on the optimisation of currently approved treatments for inflammatory bowel disease, experience with recently approved drugs in clinical practice, and some studies on molecules that are under development for the treatment of these diseases.}, }
@article {pmid27885969, year = {2016}, author = {Bateman, RM and Sharpe, MD and Jagger, JE and Ellis, CG and Solé-Violán, J and López-Rodríguez, M and Herrera-Ramos, E and Ruíz-Hernández, J and Borderías, L and Horcajada, J and González-Quevedo, N and Rajas, O and Briones, M and Rodríguez de Castro, F and Rodríguez Gallego, C and Esen, F and Orhun, G and Ergin Ozcan, P and Senturk, E and Ugur Yilmaz, C and Orhan, N and Arican, N and Kaya, M and Kucukerden, M and Giris, M and Akcan, U and Bilgic Gazioglu, S and Tuzun, E and Riff, R and Naamani, O and Douvdevani, A and Takegawa, R and Yoshida, H and Hirose, T and Yamamoto, N and Hagiya, H and Ojima, M and Akeda, Y and Tasaki, O and Tomono, K and Shimazu, T and Ono, S and Kubo, T and Suda, S and Ueno, T and Ikeda, T and Hirose, T and Ogura, H and Takahashi, H and Ojima, M and Kang, J and Nakamura, Y and Kojima, T and Shimazu, T and Ikeda, T and Suda, S and Izutani, Y and Ueno, T and Ono, S and Taniguchi, T and O, M and Dinter, C and Lotz, J and Eilers, B and Wissmann, C and Lott, R and Meili, MM and Schuetz, PS and Hawa, H and Sharshir, M and Aburageila, M and Salahuddin, N and Chantziara, V and Georgiou, S and Tsimogianni, A and Alexandropoulos, P and Vassi, A and Lagiou, F and Valta, M and Micha, G and Chinou, E and Michaloudis, G and Kodaira, A and Ikeda, T and Ono, S and Ueno, T and Suda, S and Izutani, Y and Imaizumi, H and De la Torre-Prados, MV and Garcia-De la Torre, A and Enguix-Armada, A and Puerto-Morlan, A and Perez-Valero, V and Garcia-Alcantara, A and Bolton, N and Dudziak, J and Bonney, S and Tridente, A and Nee, P and Nicolaes, G and Wiewel, M and Schultz, M and Wildhagen, K and Horn, J and Schrijver, R and Van der Poll, T and Reutelingsperger, C and Pillai, S and Davies, G and Mills, G and Aubrey, R and Morris, K and Williams, P and Evans, P and Gayat, EG and Struck, J and Cariou, A and Deye, N and Guidet, B and Jabert, S and Launay, J and Legrand, M and Léone, M and Resche-Rigon, M and Vicaut, E and Vieillard-Baron, A and Mebazaa, A and Arnold, R and Capan, M and Linder, A and Akesson, P and Popescu, M and Tomescu, D and Sprung, CL and Calderon Morales, R and Munteanu, G and Orenbuch-Harroch, E and Levin, P and Kasdan, H and Reiter, A and Volker, T and Himmel, Y and Cohen, Y and Meissonnier, J and Girard, L and Rebeaud, F and Herrmann, I and Delwarde, B and Peronnet, E and Cerrato, E and Venet, F and Lepape, A and Rimmelé, T and Monneret, G and Textoris, J and Beloborodova, N and Moroz, V and Osipov, A and Bedova, A and Sarshor, Y and Pautova, A and Sergeev, A and Chernevskaya, E and Odermatt, J and Bolliger, R and Hersberger, L and Ottiger, M and Christ-Crain, M and Mueller, B and Schuetz, P and Sharma, NK and Tashima, AK and Brunialti, MK and Machado, FR and Assuncao, M and Rigato, O and Salomao, R and Cajander, SC and Rasmussen, G and Tina, E and Söderquist, B and Källman, J and Strålin, K and Lange, AL and Sundén-Cullberg, JS and Magnuson, AM and Hultgren, OH and Davies, G and Pillai, S and Mills, G and Aubrey, R and Morris, K and Williams, P and Evans, P and Pillai, S and Davies, G and Mills, G and Aubrey, R and Morris, K and Williams, P and Evans, P and Pillai, S and Davies, G and Mills, G and Aubrey, R and Morris, K and Williams, P and Evans, P and Van der Geest, P and Mohseni, M and Linssen, J and De Jonge, R and Duran, S and Groeneveld, J and Miller, R and Lopansri, BK and McHugh, LC and Seldon, A and Burke, JP and Johnston, J and Reece-Anthony, R and Bond, A and Molokhia, A and Mcgrath, C and Nsutebu, E and Bank Pedersen, P and Pilsgaard Henriksen, D and Mikkelsen, S and Touborg Lassen, A and Tincu, R and Cobilinschi, C and Tomescu, D and Ghiorghiu, Z and Macovei, R and Wiewel, MA and Harmon, MB and Van Vught, LA and Scicluna, BP and Hoogendijk, AJ and Horn, J and Zwinderman, AH and Cremer, OL and Bonten, MJ and Schultz, MJ and Van der Poll, T and Juffermans, NP and Wiersinga, WJ and Eren, G and Tekdos, Y and Dogan, M and Acicbe, O and Kaya, E and Hergunsel, O and Alsolamy, S and Ghamdi, G and Alswaidan, L and Alharbi, S and Alenezi, F and Arabi, Y and Heaton, J and Boyce, A and Nolan, L and Johnston, J and Dukoff-Gordon, A and Dean, A and Molokhia, A and Mann Ben Yehudah, T and Fleischmann, C and Thomas-Rueddel, D and Haas, C and Dennler, U and Reinhart, K and Suntornlohanakul, O and Khwannimit, B and Breckenridge, F and Puxty, A and Szturz, P and Folwarzcny, P and Svancara, J and Kula, R and Sevcik, P and Caneva, L and Casazza, A and Bellazzi, E and Marra, S and Pagani, L and Vetere, M and Vanzino, R and Ciprandi, D and Preda, R and Boschi, R and Carnevale, L and Lopez, V and Aguilar Arzapalo, M and Barradas, L and Escalante, A and Gongora, J and Cetina, M and Adamik, B and Jakubczyk, D and Kübler, A and Radford, A and Lee, T and Singer, J and Boyd, J and Fineberg, D and Williams, M and Russell, J and Scarlatescu, E and Tomescu, D and Droc, G and Arama, S and Müller, M and Straat, M and Zeerleder, SS and Juffermans, NP and Fuchs, CF and Scheer, CS and Wauschkuhn, SW and Vollmer, MV and Meissner, KM and Kuhn, SK and Hahnenkamp, KH and Rehberg, SR and Gründling, MG and Yamamoto, N and Ojima, M and Hamaguchi, S and Hirose, T and Akeda, Y and Takegawa, R and Tasaki, O and Shimazu, T and Tomono, K and Gómez-Sánchez, E and Heredia-Rodríguez, M and Álvarez-Fuente, E and Lorenzo-López, M and Gómez-Pesquera, E and Aragón-Camino, M and Liu-Zhu, P and Sánchez-López, A and Hernández-Lozano, A and Peláez-Jareño, MT and Tamayo, E and Thomas-Rüddel, DO and Fleischmann, C and Haas, C and Dennler, U and Reinhart, K and Adora, V and Kar, A and Chakraborty, A and Roy, S and Bandyopadhyay, A and Das, M and Mann Ben Yehudah, T and BenYehudah, G and Salim, M and Kumar, N and Arabi, L and Burger, T and Lephart, P and Toth-martin, E and Valencia, C and Hammami, N and Blot, S and Vincent, JL and Lambert, ML and Brunke, J and Riemann, T and Roschke, I and Tincu, R and Cobilinschi, C and Tomescu, D and Ghiorghiu, Z and Macovei, R and Nimitvilai, S and Jintanapramote, K and Jarupongprapa, S and Adukauskiene, D and Valanciene, D and Bose, G and Lostarakos, V and Carr, B and Khedher, S and Maaoui, A and Ezzamouri, A and Salem, M and Chen, J and Cranendonk, DR and Van Vught, LA and Wiewel, MA and Cremer, OL and Horn, J and Bonten, MJ and Schultz, MJ and Van der Poll, T and Wiersinga, WJ and Day, M and Penrice, G and Roy, K and Robertson, P and Godbole, G and Jones, B and Booth, M and Donaldson, L and Kawano, Y and Ishikura, H and Al-Dorzi, H and Almutairi, M and Alhamadi, B and Crizaldo Toledo, A and Khan, R and Al Raiy, B and Arabi, Y and Talaie, H and Van Oers, JA and Harts, A and Nieuwkoop, E and Vos, P and Boussarsar, Y and Boutouta, F and Kamoun, S and Mezghani, I and Koubaji, S and Ben Souissi, A and Riahi, A and Mebazaa, MS and Giamarellos-Bourboulis, E and Tziolos, N and Routsi, C and Katsenos, C and Tsangaris, I and Pneumatikos, I and Vlachogiannis, G and Theodorou, V and Prekates, A and Antypa, E and Koulouras, V and Kapravelos, N and Gogos, C and Antoniadou, E and Mandragos, K and Armaganidis, A and Robles Caballero, AR and Civantos, B and Figueira, JC and López, J and Silva-Pinto, A and Ceia, F and Sarmento, A and Santos, L and Almekhlafi, G and Sakr, Y and Al-Dorzi, H and Khan, R and Baharoon, S and Aldawood, A and Matroud, A and Alchin, J and Al Johani, S and Balkhy, H and Arabi, Y and Alsolamy, S and Yousif, SY and Alotabi, BO and Alsaawi, AS and Ang, J and Curran, MD and Enoch, D and Navapurkar, V and Morris, A and Sharvill, R and Astin, J and Heredia-Rodríguez, M and Gómez-Sánchez, E and Peláez-Jareño, MT and Gómez-Pesquera, E and Lorenzo-López, M and Liu-Zhu, P and Aragón-Camino, M and Hernández-Lozano, A and Sánchez-López, A and Álvarez-Fuente, E and Tamayo, E and Patel, J and Kruger, C and O’Neal, J and Rhodes, H and Jancik, J and François, B and Laterre, PF and Eggimann, P and Torres, A and Sánchez, M and Dequin, PF and Bassi, GL and Chastre, J and Jafri, HS and Ben Romdhane, M and Douira, Z and Kamoun, S and Bousselmi, M and Ben Souissi, A and Boussarsar, Y and Riahi, A and Mebazaa, MS and Vakalos, A and Avramidis, V and Craven, TH and Wojcik, G and Kefala, K and McCoubrey, J and Reilly, J and Paterson, R and Inverarity, D and Laurenson, I and Walsh, TS and Mongodi, S and Bouhemad, B and Orlando, A and Stella, A and Via, G and Iotti, G and Braschi, A and Mojoli, F and Haliloglu, M and Bilgili, B and Kasapoglu, U and Sayan, I and Süzer Aslan, M and Yalcın, A and Cinel, I and Vakalos, A and Avramidis, V and Ellis, HE and Bauchmuller, K and Miller, D and Temple, A and Chastre, J and François, B and Torres, A and Luyt, CE and Sánchez, M and Singer, M and Jafri, HS and Nassar, Y and Ayad, MS and Trifi, A and Abdellatif, S and Daly, F and Nasri, R and Ben Lakhal, S and Bilgili, B and Haliloglu, M and Gul, F and Cinel, I and Kuzovlev, A and Shabanov, A and Polovnikov, S and Moroz, V and Kadrichu, N and Dang, T and Corkery, K and Challoner, P and Bassi, GL and Aguilera, E and Chiurazzi, C and Travierso, C and Motos, A and Fernandez, L and Amaro, R and Senussi, T and Idone, F and Bobi, J and Rigol, M and Torres, A and Hodiamont, CJ and Juffermans, NP and Janssen, JM and Bouman, CS and Mathôt, RA and De Jong, MD and Van Hest, RM and Payne, L and Fraser, GL and Tudor, B and Lahner, M and Roth, G and Krenn, C and Talaie, H and Jault, P and Gabard, J and Leclerc, T and Jennes, S and Que, Y and Rousseau, A and Ravat, F and Al-Dorzi, H and Eissa, A and Al-Harbi, S and Aldabbagh, T and Khan, R and Arabi, Y and Trifi, A and Abdellatif., S and Daly, F and Nasri, R and Ben Lakhal, S and Paramba, F and Purayil, N and Naushad, V and Mohammad, O and Negi, V and Chandra, P and Kleinsasser, A and Witrz, MR and Buchner-Doeven, JF and Tuip-de Boer, AM and Goslings, JC and Juffermans, NP and Van Hezel, M and Straat, M and Boing, A and Van Bruggen, R and Juffermans, N and Markopoulou, D and Venetsanou, K and Kaldis, V and Koutete, D and Chroni, D and Alamanos, I and Koch, L and Jancik, J and Rhodes, H and Walter, E and Maekawa, K and Hayakawa, M and Kushimoto, S and Shiraishi, A and Kato, H and Sasaki, J and Ogura, H and Matauoka, T and Uejima, T and Morimura, N and Ishikura, H and Hagiwara, A and Takeda, M and Tarabrin, O and Shcherbakow, S and Gavrychenko, D and Mazurenko, G and Ivanova, V and Chystikov, O and Plourde, C and Lessard, J and Chauny, J and Daoust, R and Shcherbakow, S and Tarabrin, O and Gavrychenko, D and Mazurenko, G and Chystikov, O and Vakalos, A and Avramidis, V and Kropman, L and In het Panhuis, L and Konings, J and Huskens, D and Schurgers, E and Roest, M and De Laat, B and Lance, M and Durila, M and Lukas, P and Astraverkhava, M and Jonas, J and Budnik, I and Shenkman, B and Hayami, H and Koide, Y and Goto, T and Iqbal, R and Alhamdi, Y and Venugopal, N and Abrams, S and Downey, C and Toh, CH and Welters, ID and Bombay, VB and Chauny, JM and Daoust, RD and Lessard, JL and Marquis, MM and Paquet, JP and Siemens, K and Sangaran, D and Hunt, BJ and Durward, A and Nyman, A and Murdoch, IA and Tibby, SM and Ampatzidou, F and Moisidou, D and Dalampini, E and Nastou, M and Vasilarou, E and Kalaizi, V and Chatzikostenoglou, H and Drossos, G and Spadaro, S and Fogagnolo, A and Fiore, T and Schiavi, A and Fontana, V and Taccone, F and Volta, C and Chochliourou, E and Volakli, E and Violaki, A and Samkinidou, E and Evlavis, G and Panagiotidou, V and Sdougka, M and Mothukuri, R and Battle, C and Guy, K and Mills, G and Evans, P and Wijesuriya, J and Keogh, S and Docherty, A and O’Donnell, R and Brunskill, S and Trivella, M and Doree, C and Holst, L and Parker, M and Gregersen, M and Almeida, J and Walsh, T and Stanworth, S and Moravcova, S and Mansell, J and Rogers, A and Smith, RA and Hamilton-Davies, C and Omar, A and Allam, M and Bilala, O and Kindawi, A and Ewila, H and Ampatzidou, F and Moisidou, D and Nastou, M and Dalampini, E and Malamas, A and Vasilarou, E and Drossos, G and Ferreira, G and Caldas, J and Fukushima, J and Osawa, EA and Arita, E and Camara, L and Zeferino, S and Jardim, J and Gaioto, F and Dallan, L and Jatene, FB and Kalil Filho, R and Galas, F and Hajjar, LA and Mitaka, C and Ohnuma, T and Murayama, T and Kunimoto, F and Nagashima, M and Takei, T and Tomita, M and Omar, A and Mahmoud, K and Hanoura, S and Sudarsanan, S and Sivadasan, P and Othamn, H and Shouman, Y and Singh, R and Al Khulaifi, A and Mandel, I and Mikheev, S and Suhodolo, I and Kiselev, V and Svirko, Y and Podoksenov, Y and Jenkins, SA and Griffin, R and Tovar Doncel, MS and Lima, A and Aldecoa, C and Ince, C and Taha, A and Shafie, A and Mostafa, M and Syed, N and Hon, H and Righetti, F and Colombaroli, E and Castellano, G and Righetti, F and Colombaroli, E and Hravnak, M and Chen, LC and Dubrawski, AD and Clermont, GC and Pinsky, MR and Gonzalez, S and Macias, D and Acosta, J and Jimenez, P and Loza, A and Lesmes, A and Lucena, F and Leon, C and Tovar Doncel, MS and Ince, C and 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and Takala, J and Berger, D and Bastoni, D and Aya, H and Toscani, L and Pigozzi, L and Rhodes, A and Cecconi, M and Ostrowska, C and Aya, H and Abbas, A and Mellinghoff, J and Ryan, C and Dawson, D and Rhodes, A and Cecconi, M and Cronhjort, M and Wall, O and Nyberg, E and Zeng, R and Svensen, C and Mårtensson, J and Joelsson-Alm, E and Aguilar Arzapalo, M and Barradas, L and Lopez, V and Cetina, M and Parenti, N and Palazzi, C and Amidei, LA and Borrelli, FB and Campanale, SC and Tagliazucchi, FT and Sedoni, GS and Lucchesi, DL and Carella, EC and Luciani, AL and Mackovic, M and Maric, N and Bakula, M and Aya, H and Rhodes, A and Grounds, RM and Fletcher, N and Cecconi, M and Avard, B and Zhang, P and Mezidi, M and Charbit, J and Ould-Chikh, M and Deras, P and Maury, C and Martinez, O and Capdevila, X and Hou, P and Linde-Zwirble, WZ and Douglas, ID and Shapiro, NS and Ben Souissi, A and Mezghani, I and Ben Aicha, Y and Kamoun, S and Laribi, B and Jeribi, B and Riahi, A and Mebazaa, 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Sell, A and Lin, S and Torrence, H and O’Dwyer, M and Kirwan, C and Prowle, J and Kim, T and O’Connor, ME and Hewson, RW and Kirwan, CJ and Pearse, RM and Prowle, J and Hanoura, S and Omar, A and Othamn, H and Sudarsanan, S and Allam, M and Maksoud, M and Singh, R and Al Khulaifi, A and O’Connor, ME and Hewson, RW and Kirwan, CJ and Pearse, RM and Prowle, J and Uzundere, O and Memis, D and Ýnal, M and Gultekin, A and Turan, N and Aydin, MA and Basar, H and Sencan, I and Kapuagasi, A and Ozturk, M and Uzundurukan, Z and Gokmen, D and Ozcan, A and Kaymak, C and Artemenko, VA and Budnyuk, A and Pugh, R and Bhandari, S and Mauri, T and Turrini, C and Langer, T and Taccone, P and Volta, CA and Marenghi, C and Gattinoni, L and Pesenti, A and Sweeney, L and O’Sullivan, A and Kelly, P and Mukeria, E and MacLoughlin, R and Pfeffer, M and Thomas, JT and Bregman, GB and Karp, GK and Kishinevsky, EK and Stavi, DS and Adi, NA and Poropat, T and Knafelj, R and Llopart, E and Batlle, M and De Haro, C and Mesquida, J and Artigas, A and Pavlovic, D and Lewerentz, L and Spassov, A and Schneider, R and De Smet, S and De Raedt, S and Derom, E and Depuydt, P and Oeyen, S and Benoit, D and Decruyenaere, J and Gobatto, A and Besen, B and Tierno, P and Melro, L and Mendes, P and Cadamuro, F and Park, M and Malbouisson, LM and Civantos, BC and Lopez, JL and Robles, A and Figueira, J and Yus, S and Garcia, A and Oglinda, A and Ciobanu, G and Oglinda, C and Schirca, L and Sertinean, T and Lupu, V and Kelly, P and O’Sullivan, A and Sweeney, L and MacLoughlin, R and O’Sullivan, A and Kelly, P and Sweeney, L and Mukeria, E and Wolny, M and MacLoughlin, R and Pagano, A and Numis, F and Visone, G and Saldamarco, L and Russo, T and Porta, G and Paladino, F and Bell, C and Liu, J and Debacker, J and Lee, C and Tamberg, E and Campbell, V and Mehta, S and Silva-Pinto, A and Sarmento, A and Santos, L and Kara, &#xdd; and Yýldýrým, F and Zerman, A and Güllü, Z and Boyacý, N and Basarýk Aydogan, B and 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and Alcorn, S and McNeill, S and Russell, S and Eertmans, W and Genbrugge, C and Meex, I and Dens, J and Jans, F and De Deyne, C and Cholkraisuwat, J and Kongpolprom, N and Avard, B and Burns, R and Patarchi, A and Spina, T and Tanaka, H and Otani, N and Ode, S and Ishimatsu, S and Cho, J and Moon, JB and Park, CW and Ohk, TG and Shin, MC and Won, MH and Dakova, S and Ramsheva, Z and Ramshev, K and Cho, J and Moon, JB and Park, CW and Ohk, TG and Shin, MC and Cho, J and Moon, JB and Park, CW and Ohk, TG and Shin, MC and Marudi, A and Baroni, S and Gaspari, A and Bertellini, E and Orhun, G and Senturk, E and Ozcan, PE and Sencer, S and Ulusoy, C and Tuzun, E and Esen, F and Tincu, R and Cobilinschi, C and Tomescu, D and Ghiorghiu, Z and Macovei, R and Van Assen, M and Admiraal, MM and Van Putten, MJ and Tjepkema-Cloostermans, M and Van Rootselaar, AF and Horn, J and Fallenius, M and Skrifvars, MB and Reinikainen, M and Bendel, S and Raj, R and Abu-Habsa, M and Hymers, C and Borowska, A 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Spatenkova, V and Pokorna, E and Suchomel, P and Ebert, N and Jancik, J and Rhodes, H and Bylinski, T and Hawthorne, C and Shaw, M and Piper, I and Kinsella, J and Kink, AK and Rätsep, IR and Boutin, A and Moore, L and Chasse, M and Zarychanski, R and Lauzier, F and English, S and McIntyre, L and Lacroix, J and Griesdale, D and Lessard-Bonaventure, P and Turgeon, AF and Boutin, A and Moore, L and Green, R and Lessard-Bonaventure, P and Erdogan, M and Butler, M and Lauzier, F and Chasse, M and English, S and McIntyre, L and Zarychanski, R and Lacroix, J and Griesdale, D and Desjardins, P and Fergusson, DA and Turgeon, AF and Goncalves, B and Vidal, B and Valdez, C and Rodrigues, AC and Miguez, L and Moralez, G and Hong, T and Kutz, A and Hausfater, P and Amin, D and Struja, T and Haubitz, S and Huber, A and Mueller, B and Schuetz, P and Brown, T and Collinson, J and Pritchett, C and Slade, T and Le Guen, M and Hellings, S and Ramsaran, R and Alsheikhly, A and Abe, T and Kanapeckaite, L and Abu-Habsa, M and Bahl, R and Russell, MQ and Real, KJ and Abu-Habsa, M and Lyon, RM and Oveland, NP and Penketh, J and Mcdonald, M and Kelly, F and Alfafi, M and Alsolamy, S and Almutairi, W and Alotaibi, B and Van den Berg, AE and Schriel, Y and Dawson, L and Meynaar, IA and Talaie, H and Silva, D and Fernandes, S and Gouveia, J and Santos Silva, J and Foley, J and Kaskovagheorgescu, A and Evoy, D and Cronin, J and Ryan, J and Huck, M and Hoffmann, C and Renner, J and Laitselart, P and Donat, N and Cirodde, A and Schaal, JV and Masson, Y and Nau, A and Leclerc, T and Howarth, O and Davenport, K and Jeanrenaud, P and Raftery, S and MacTavish, P and Devine, H and McPeake, J and Daniel, M and Kinsella, J and Quasim, T and Alrabiee, S and Alrashid, A and Alsolamy, S and Gundogan, O and Bor, C and Akýn Korhan, E and Demirag, K and Uyar, M and Frame, F and Ashton, C and Bergstrom Niska, L and Dilokpattanamongkol, P and Suansanae, T and Suthisisang, C and Morakul, S and Karnjanarachata, C and Tangsujaritvijit, V and Mahmood, S and Al Thani, H and Almenyar, A and Vakalos, A and Avramidis, V and Sharvill, R and Penketh, J and Morton, SE and Chiew, YS and Pretty, C and Chase, JG and Shaw, GM and Knafelj, R and Kordis, P and Patel, S and Grover, V and Kuchyn, I and Bielka, K and Aidoni, Z and Grosomanidis, V and Kotzampassi, K and Stavrou, G and Fyntanidou, B and Patsatzakis, S and Skourtis, C and Lee, SD and Williams, K and Weltes, ID and Berhane, S and Arrowsmith, C and Peters, C and Robert, S and Caldas, J and Panerai, RB and Robinson, TG and Camara, L and Ferreira, G and Borg-Seng-Shu, E and De Lima Oliveira, M and Mian, NC and Santos, L and Nogueira, R and Zeferino, SP and Jacobsen Teixeira, M and Galas, F and Hajjar, LA and Killeen, P and McPhail, M and Bernal, W and Maggs, J and Wendon, J and Hughes, T and Taniguchi, LU and Siqueira, EM and Vieira Jr, JM and Azevedo, LC and Ahmad, AN and Abu-Habsa, M and Bahl, R and Helme, E and Hadfield, S and Loveridge, R and Shak, J and Senver, C and Howard-Griffin, R and Wacharasint, P and Fuengfoo, P and Sukcharoen, N and Rangsin, R and Sbiti-Rohr, D and Schuetz, P and Na, H and Song, S and Lee, S and Jeong, E and Lee, K and Cooper, M and Milinis, K and Williams, G and McCarron, E and Simants, S and Patanwala, I and Welters, ID and Zoumpelouli, E and Volakli, EA and Chrysohoidou, V and Georgiou, S and Charisopoulou, K and Kotzapanagiotou, E and Panagiotidou, V and Manavidou, K and Stathi, Z and Sdougka, M and Salahuddin, N and AlGhamdi, B and Marashly, Q and Zaza, K and Sharshir, M and Khurshid, M and Ali, Z and Malgapo, M and Jamil, M and Shafquat, A and Shoukri, M and Hijazi, M and Abe, T and Uchino, S and Takinami, M and Rangel Neto, NR and Oliveira, S and Reis, FQ and Rocha, FA and Moralez, G and Ebecken, K and Rabello, LS and Lima, MF and Hatum, R and De Marco, FV and Alves, A and Pinto, JE and Godoy, M and Brasil, PE and Bozza, FA and Salluh, JI and Soares, M and Krinsley, J and Kang, G and Perry, J and Hines, H and Wilkinson, KM and Tordoff, C and Sloan, B and Bellamy, MC and Moreira, E and Verga, F and Barbato, M and Burghi, G and Soares, M and Silva, UV and Azevedo, LC and Torelly, AP and Kahn, JM and Angus, DC and Knibel, MF and Brasil, PE and Bozza, FA and Salluh, JI and Velasco, MB and Dalcomune, DM and Marshall, R and Gilpin, T and Tridente, A and Raithatha, A and Mota, D and Loureiro, B and Dias, J and Afonso, O and Coelho, F and Martins, A and Faria, F and Al-Dorzi, H and Al Orainni, H and AlEid, F and Tlaygeh, H and Itani, A and Hejazi, A and Arabi, Y and Gaudry, S and Messika, J and Ricard, JD and Guillo, S and Pasquet, B and Dubief, E and Dreyfuss, D and Tubach, F and Battle, C and James, K and Temblett, P and Davies, L and Battle, C and Lynch, C and Pereira, S and Cavaco, S and Fernandes, J and Moreira, I and Almeida, E and Seabra Pereira, F and Malheiro, M and Cardoso, F and Aragão, I and Cardoso, T and Fister, M and Knafelj, R and Muraray Govind, P and Brahmananda Reddy, N and Pratheema, R and Arul, ED and Devachandran, J and Velasco, MB and Dalcomune, DM and Knafelj, R and Fister, M and Chin-Yee, N and D’Egidio, G and Thavorn, K and Heyland, D and Kyeremanteng, K and Murchison, AG and Swalwell, K and Mandeville, J and Stott, D and Guerreiro, I and Devine, H and MacTavish, P and McPeake, J and Quasim, T and Kinsella, J and Daniel, M and Goossens, C and Marques, MB and Derde, S and Vander Perre, S and Dufour, T and Thiessen, SE and Güiza, F and Janssens, T and Hermans, G and Vanhorebeek, I and De Bock, K and Van den Berghe, G and Langouche, L and Devine, H and MacTavish, P and Quasim, T and Kinsella, J and Daniel, M and McPeake, J and Miles, B and Madden, S and Devine, H and Weiler, M and Marques, P and Rodrigues, C and Boeira, M and Brenner, K and Leães, C and Machado, A and Townsend, R and Andrade, J and MacTavish, P and McPeake, J and Devine, H and Kinsella, J and Daniel, M and Kishore, R and Fenlon, C and Quasim, T and Fiks, T and Ruijter, A and Te Raa, M and Spronk, P and Chiew, YS and Docherty, P and Dickson, J and Moltchanova, E and Scarrot, C and Pretty, C and Shaw, GM and Chase, JG and Hall, T and Ngu, WC and Jack, JM and Morgan, P and Avard, B and Pavli, A and Gee, X and Bor, C and Akin Korhan, E and Demirag, K and Uyar, M and Shirazy, M and Fayed, A and Gupta, S and Kaushal, A and Dewan, S and Varma, A and Ghosh, E and Yang, L and Eshelman, L and Lord, B and Carlson, E and Helme, E and Broderick, R and Hadfield, S and Loveridge, R and Ramos, J and Forte, D and Yang, F and Hou, P and Dudziak, J and Feeney, J and Wilkinson, K and Bauchmuller, K and Shuker, K and Faulds, M and Raithatha, A and Bryden, D and England, L and Bolton, N and Tridente, A and Bauchmuller, K and Shuker, K and Tridente, A and Faulds, M and Matheson, A and Gaynor, J and Bryden, D and ,  and Ramos, J and Peroni, B and Daglius-Dias, R and Miranda, L and Cohen, C and Carvalho, C and Velasco, I and Forte, D and Kelly, JM and Neill, A and Rubenfeld, G and Masson, N and Min, A and Boezeman, E and Hofhuis, J and Hovingh, A and De Vries, R and Spronk, P and Cabral-Campello, G and Aragão, I and Cardoso, T and Van Mol, M and Nijkamp, M and Kompanje, E and Ostrowski, P and Omar, A and Kiss, K and Köves, B and Csernus, V and Molnár, Z and Hoydonckx, Y and Vanwing, S and Stessel, B and Van Assche, A and Jamaer, L and Dubois, J and Medo, V and Galvez, R and Miranda, JP and Stone, C and Wigmore, T and Arunan, Y and Wheeler, A and Bauchmuller, K and Bryden, D and Wong, Y and Poi, C and Gu, C and Molmy, P and Van Grunderbeeck, N and Nigeon, O and Lemyze, M and Thevenin, D and Mallat, J and Ramos, J and Correa, M and Carvalho, RT and Forte, D and Fernandez, A and McBride, C and Koonthalloor, E and Walsh, C and Webber, A and Ashe, M and Smith, K and Jeanrenaud, P and Marudi, A and Baroni, S and Ragusa, F and Bertellini, E and Volakli, EA and Chochliourou, E and Dimitriadou, M and Violaki, A and Mantzafleri, P and Samkinidou, E and Vrani, O and Arbouti, A and Varsami, T and Sdougka, M and Bollen, JA and Van Smaalen, TC and De Jongh, WC and Ten Hoopen, MM and Ysebaert, D and Van Heurn, LW and Van Mook, WN and Sim, K and Fuller, A and Roze des Ordons, A and Couillard, P and Doig, C and Van Keer, RV and Deschepper, RD and Francke, AF and Huyghens, LH and Bilsen, JB and Nyamaizi, B and Dalrymple, C and Molokhia, A and Dobru, A and Marrinan, E and Ankuli, A and Molokhia, A and McPeake, J and Struthers, R and Crawford, R and Devine, H and Mactavish, P and Quasim, T and Morelli, P and Degiovanangelo, M and Lemos, F and MArtinez, V and Verga, F and Cabrera, J and Burghi, G and Rutten, A and Van Ieperen, S and De Geer, S and Van Vugt, M and Der Kinderen, E and Giannini, A and Miccinesi, G and Marchesi, T and Prandi, E}, title = {36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.}, journal = {Critical care (London, England)}, volume = {20}, number = {Suppl 2}, pages = {94}, doi = {10.1186/s13054-016-1208-6}, pmid = {27885969}, issn = {1466-609X}, }
@article {pmid27885481, year = {2017}, author = {Koriche, D and Gower-Rousseau, C and Chater, C and Duhamel, A and Salleron, J and Tavernier, N and Colombel, JF and Pariente, B and Cortot, A and Zerbib, P}, title = {Post-operative recurrence of Crohn's disease after definitive stoma: an underestimated risk.}, journal = {International journal of colorectal disease}, volume = {32}, number = {4}, pages = {453-458}, pmid = {27885481}, issn = {1432-1262}, mesh = {Adolescent ; Adult ; Aged ; Child ; Crohn Disease/*surgery ; Demography ; Female ; Humans ; Male ; Middle Aged ; Postoperative Complications/*etiology ; Recurrence ; Risk Factors ; Surgical Stomas/*adverse effects ; Treatment Outcome ; Young Adult ; }, abstract = {INTRODUCTION: Crohn's disease (CD) is a progressive inflammatory disease affecting the entire gastrointestinal tract. The need for a definitive stoma (DS) is considered as the ultimate phase of damage. It is often believed that the risk of further disease progression is small when a DS has been performed.<br><br>AIMS: The goals of the study were to establish the rate of CD recurrence above the DS and to identify predictive factors of CD recurrence at the time of DS.<br><br>METHODS: We retrospectively reviewed all medical records of consecutive CD patients having undergone DS between 1973 and 2010. We collected clinical data at diagnosis, CD phenotype, treatment, and surgery after DS and mortality. Stoma was considered as definitive when restoration of continuity was not possible due to proctectomy, rectitis, anoperineal lesions (APL), or fecal incontinence. Clinical recurrence (CR) was defined as the need for re-introduction or intensification of medical therapy, and surgical recurrence (SR) was defined as a need for a new intestinal resection.<br><br>RESULTS: Eighty-three patients (20 males, 63 females) with a median age of 34&#xa0;years at CD diagnosis were included. The median time between diagnosis and DS was 9&#xa0;years. The median follow-up after DS was 10&#xa0;years. Thirty-five patients (42%) presented a CR after a median time of 28&#xa0;months (2-211) and 32 patients (38%) presented a SR after a median time of 29&#xa0;months (4-212). In a multivariate analysis, APL (HR&#xa0;=&#xa0;5.1 (1.2-21.1), p&#xa0;=&#xa0;0.03) and colostomy at time of DS (HR&#xa0;=&#xa0;3.8 (1.9-7.3), p&#xa0;=&#xa0;0.0001) were associated factors with the CR.<br><br>CONCLUSION: After DS for CD, the risk of clinical recurrence was high and synonymous with surgical recurrence, especially for patients with APL and colostomy.}, }
@article {pmid27879485, year = {2017}, author = {Zeitz, J and Bissig, M and Barthel, C and Biedermann, L and Scharl, S and Pohl, D and Frei, P and Vavricka, SR and Fried, M and Rogler, G and Scharl, M}, title = {Patients' views on fecal microbiota transplantation: an acceptable therapeutic option in inflammatory bowel disease?.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {29}, number = {3}, pages = {322-330}, doi = {10.1097/MEG.0000000000000783}, pmid = {27879485}, issn = {1473-5687}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Choice Behavior ; Colitis, Ulcerative/microbiology/psychology/*therapy ; Colonoscopy/psychology ; Crohn Disease/microbiology/psychology/*therapy ; Fear/psychology ; Fecal Microbiota Transplantation/adverse effects/methods/*psychology ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; *Patient Acceptance of Health Care ; Patient Preference ; Risk Factors ; Surveys and Questionnaires ; Tissue Donors/supply &amp; distribution ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) represents a new therapeutic option that has been studied in two randomized-controlled trials in ulcerative colitis patients. Our study aimed to identify patients' views on the use of this novel therapeutic approach.<br><br>METHODS: Using an anonymous questionnaire, we obtained data from 574 inflammatory bowel disease (IBD) patients on their knowledge and willingness to undergo FMT.<br><br>RESULTS: A large proportion of IBD patients (53.5%) are unaware that FMT is a therapeutic option in Clostridium difficile infection and potentially IBD. More responders preferred FMT (31.5%) to a study with a new medication (28.9%), although the difference was not significant (P=0.37), and the preferred way of transplantation was colonoscopy (49.7%). In all, 38.3% preferred a family member as a donor, but there was fear about the procedure (41.5% mentioned fear of infectious diseases, 26.5% expressed disgust). The knowledge of successful FMT treatment in other patients was important for 82.2% of responders and for 50.7%, a discussion with a specialist would likely change their opinion about FMT.<br><br>CONCLUSION: FMT represents a therapeutic procedure that is of interest for IBD patients. As FMT has been receiving increasing interest as an alternative treatment in IBD and more studies on FMT in IBD are being carried out, it is important to learn about the knowledge, attitude, and preferences of patients to provide better education to patients on this topic. However, there are reservations because of the fact that data on the benefits of FMT in IBD are controversial and several limitations exist on the use of FMT in IBD.}, }
@article {pmid27879260, year = {2017}, author = {Josefsdottir, KS and Baldridge, MT and Kadmon, CS and King, KY}, title = {Antibiotics impair murine hematopoiesis by depleting the intestinal microbiota.}, journal = {Blood}, volume = {129}, number = {6}, pages = {729-739}, pmid = {27879260}, issn = {1528-0020}, support = {U19 AI109725/AI/NIAID NIH HHS/United States ; R01 AI141716/AI/NIAID NIH HHS/United States ; T32 CA009547/CA/NCI NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; }, mesh = {Anemia/*chemically induced/microbiology/pathology/therapy ; Animals ; Anti-Bacterial Agents/*adverse effects ; B-Lymphocytes/drug effects/metabolism/pathology ; Bone Marrow Cells/drug effects/metabolism/pathology ; CD8-Positive T-Lymphocytes/drug effects/metabolism/pathology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects/physiology ; Gene Expression ; Germ-Free Life/drug effects/genetics ; Granulocytes/drug effects/metabolism/pathology ; Hematopoiesis/*drug effects/genetics ; Hematopoietic Stem Cells/drug effects/metabolism/pathology ; Leukopenia/*chemically induced/microbiology/pathology/therapy ; Macrophages/drug effects/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; STAT1 Transcription Factor/deficiency/*genetics ; Signal Transduction ; Thrombocytosis/*chemically induced/microbiology/pathology/therapy ; }, abstract = {Bone marrow suppression is an adverse effect associated with many antibiotics, especially when administered for prolonged treatment courses. Recent advances in our understanding of steady-state hematopoiesis have allowed us to explore the effects of antibiotics on hematopoietic progenitors in detail using a murine model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia, with pronounced pan-lymphopenia as demonstrated by flow cytometric analysis of peripheral blood. Bone marrow progenitor analysis revealed depletion of hematopoietic stem cells and multipotent progenitors across all subtypes. Granulocytes and B cells were also diminished in the bone marrow, whereas the number of CD8[+] T cells increased. Reductions in progenitor activity were not observed when cells were directly incubated with antibiotics, suggesting that these effects are indirect. Hematopoietic changes were associated with a significant contraction of the fecal microbiome and were partially rescued by fecal microbiota transfer. Further, mice raised in germ-free conditions had hematopoietic abnormalities similar to those seen in antibiotic-treated mice, and antibiotic therapy of germ-free mice caused no additional abnormalities. The effects of antibiotics were phenocopied in Stat1-deficient mice, with no additional suppression by antibiotics in these mice. We conclude that microbiome depletion as a result of broad-spectrum antibiotic treatment disrupts basal Stat1 signaling and alters T-cell homeostasis, leading to impaired progenitor maintenance and granulocyte maturation. Methods to preserve the microbiome may reduce the incidence of antibiotic-associated bone marrow suppression.}, }
@article {pmid27876399, year = {2017}, author = {Quraishi, MN and Segal, J and Mullish, B and McCune, VL and Hawkey, P and Colville, A and Williams, H and Hart, A and Iqbal, TH}, title = {National survey of practice of faecal microbiota transplantation for Clostridium difficile infection in the UK.}, journal = {The Journal of hospital infection}, volume = {95}, number = {4}, pages = {444-445}, doi = {10.1016/j.jhin.2016.10.023}, pmid = {27876399}, issn = {1532-2939}, support = {EME/13/179/01/DH_/Department of Health/United Kingdom ; }, mesh = {*Clostridioides difficile ; Clostridium Infections ; Enterocolitis, Pseudomembranous ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Microbiota ; Surveys and Questionnaires ; }, }
@article {pmid27876339, year = {2017}, author = {Taylor, KN and McHale, MT and Saenz, CC and Plaxe, SC}, title = {Diagnosis and treatment of Clostridium difficile (C. diff) colitis: Review of the literature and a perspective in gynecologic oncology.}, journal = {Gynecologic oncology}, volume = {144}, number = {2}, pages = {428-437}, doi = {10.1016/j.ygyno.2016.11.024}, pmid = {27876339}, issn = {1095-6859}, mesh = {Bacterial Proteins/analysis ; Bacterial Toxins/analysis ; Enterocolitis, Pseudomembranous/*diagnosis/etiology/*therapy ; Enterotoxins/analysis ; Female ; Genital Neoplasms, Female/*complications ; Humans ; Nucleic Acid Amplification Techniques ; Severity of Illness Index ; }, abstract = {Clostridium difficile infection (CDI) is a major cause of nosocomial diarrhea with the potential for significant morbidity and mortality. Colonization in a susceptible individual, with risk factors such as prior antibiotic use, advanced age, or medical comorbidities, may result in symptomatic infection. Although patients with a gynecologic malignancy may be at a higher risk of developing CDI due to an increased likelihood of having one or more risk factors, data do not consistently support the idea that chemotherapy or cancer itself are independently associated with CDI. For diagnosis of CDI, we recommended using a multi-step approach, with a highly sensitive initial rapid test such as the enzyme immunoassay (EIA) for glutamate dehydrogenase (GDH) or nucleic acid amplification testing (NAAT), followed by confirmatory testing with of the above two tests or EIA toxin A/B, which has high specificity. Treatment varies based on the severity of disease. We recommend vancomycin as first-line therapy for an initial episode of mild/moderate or severe CDI, with consideration of fidaxomicin for patients at particularly high risk for recurrence. Rectal vancomycin may play an adjunctive role for some severe cases, while surgical intervention is indicated for fulminant CDI if no improvement six or more days after initiating medical therapy. For non-severe recurrent disease, the initial treatment regimen should be repeated, while subsequent episodes are more appropriately treated with a tapered and pulsed dose of vancomycin, fidaxomicin, or fecal microbiota transplantation.}, }
@article {pmid27866880, year = {2017}, author = {Ott, SJ and Waetzig, GH and Rehman, A and Moltzau-Anderson, J and Bharti, R and Grasis, JA and Cassidy, L and Tholey, A and Fickenscher, H and Seegert, D and Rosenstiel, P and Schreiber, S}, title = {Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection.}, journal = {Gastroenterology}, volume = {152}, number = {4}, pages = {799-811.e7}, doi = {10.1053/j.gastro.2016.11.010}, pmid = {27866880}, issn = {1528-0012}, mesh = {Aged ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Filtration ; Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism/virology ; Humans ; Male ; Middle Aged ; Proteome ; Recurrence ; *Sterilization ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (CDI). However, transferring undefined living bacteria entails uncontrollable risks for infectious and metabolic or malignant diseases, particularly in immunocompromised patients. We investigated whether sterile fecal filtrates (containing bacterial debris, proteins, antimicrobial compounds, metabolic products, and oligonucleotides/DNA), rather than intact microorganisms, are effective in patients with CDI.<br><br>METHODS: We performed a clinical case series to investigate the effects of fecal filtrate transfer (FFT) in 5 patients with symptomatic chronic-relapsing CDI at the Department of Internal Medicine I at the University Hospital Schleswig-Holstein (Kiel, Germany). Patients were followed up for at least 6 months and for up to 33 months. Stool was collected from 5 donors selected by the patients, and fully characterized according to FMT standards. Stool was sterile-filtered to remove small particles and bacteria; the filtrate was transferred to patients in a single administration via nasojejunal tube. Fecal samples were collected from patients before and at 1 week and 6 weeks after FFT. Microbiome, virome, and proteome profiles of donors and patients were compared.<br><br>RESULTS: In all 5 patients, FFT restored normal stool habits and eliminated symptoms of CDI for a minimum period of 6 months. Proteome analyses of selected FFT filtrates showed no obvious protein candidates associated with therapeutic efficacy. 16S ribosomal RNA gene sequencing detected diverse bacterial DNA signatures in the filtrates. Analysis of virus-like particles from a filtrate found to reduce symptoms of CDI showed a complex signature of bacteriophages. Bacterial phylogeny and virome profile analyses of fecal samples from recipients indicated longitudinal changes in microbial and viral community structures after FFT.<br><br>CONCLUSIONS: A preliminary investigation of 5 patients with CDI shows that transfer of sterile filtrates from donor stool (FFT), rather than fecal microbiota, can be sufficient to restore normal stool habits and eliminate symptoms. This finding indicates that bacterial components, metabolites, or bacteriophages mediate many of the effects of FMT, and that&#xa0;FFT might be an alternative approach, particularly for immunocompromised patients.}, }
@article {pmid27861129, year = {2017}, author = {Groen, AK and Nieuwdorp, M}, title = {An evaluation of the therapeutic potential of fecal microbiota transplantation to treat infectious and metabolic diseases.}, journal = {EMBO molecular medicine}, volume = {9}, number = {1}, pages = {1-3}, pmid = {27861129}, issn = {1757-4684}, mesh = {Biomedical Research/trends ; Clinical Trials as Topic ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Metabolic Diseases/*therapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has had a long history in medicine for treating a number of human diseases. As early as during the 4[th] century BC, FMT was used in China to treat patients with food poisoning and diarrhea. Over time, the method became obsolete, particularly after the realization that hygiene plays an important role in preventing infectious diseases. It was not until the late 1950s that FMT garnered interest again when the first reports about its use to treat fulminant enterocolitis appeared in the scientific literature. However, FMT's breakthrough as the method of choice for the treatment of persistent Clostridium difficile infection (CDI) came only after a double‐blind randomized trial (van Nood et al, 2013), which demonstrated 94% efficacy of FMT compared with 31% after conservative treatment with vancomycin.}, }
@article {pmid27861126, year = {2016}, author = {Andriessen, EM and Wilson, AM and Mawambo, G and Dejda, A and Miloudi, K and Sennlaub, F and Sapieha, P}, title = {Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization.}, journal = {EMBO molecular medicine}, volume = {8}, number = {12}, pages = {1366-1379}, pmid = {27861126}, issn = {1757-4684}, support = {324573//CIHR/Canada ; }, mesh = {Animals ; Choroidal Neovascularization/*pathology ; Cytokines/blood ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Dysbiosis/etiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Inflammation/pathology ; Macular Degeneration/epidemiology/*pathology ; Mice ; *Neovascularization, Pathologic ; Obesity/*complications/pathology ; }, abstract = {Age-related macular degeneration in its neovascular form (NV AMD) is the leading cause of vision loss among adults above the age of 60. Epidemiological data suggest that in men, overall abdominal obesity is the second most important environmental risk factor after smoking for progression to late-stage NV AMD To date, the mechanisms that underscore this observation remain ill-defined. Given the impact of high-fat diets on gut microbiota, we investigated whether commensal microbes influence the evolution of AMD Using mouse models of NV AMD, microbiotal transplants, and other paradigms that modify the gut microbiome, we uncoupled weight gain from confounding factors and demonstrate that high-fat diets exacerbate choroidal neovascularization (CNV) by altering gut microbiota. Gut dysbiosis leads to heightened intestinal permeability and chronic low-grade inflammation characteristic of inflammaging with elevated production of IL-6, IL-1β, TNF-α, and VEGF-A that ultimately aggravate pathological angiogenesis.}, }
@article {pmid27859394, year = {2017}, author = {Emilsson, L and Holme, &#xd8; and Bretthauer, M and Cook, NR and Buring, JE and Løberg, M and Adami, HO and Sesso, HD and Gaziano, MJ and Kalager, M}, title = {Systematic review with meta-analysis: the comparative effectiveness of aspirin vs. screening for colorectal cancer prevention.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {45}, number = {2}, pages = {193-204}, doi = {10.1111/apt.13857}, pmid = {27859394}, issn = {1365-2036}, mesh = {Aspirin/*therapeutic use ; Colorectal Neoplasms/diagnosis/epidemiology/*prevention &amp; control ; *Early Detection of Cancer ; Humans ; Incidence ; Mass Screening ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Both aspirin use and screening with flexible sigmoidoscopy or guaiac faecal occult blood testing (FOBT) may reduce mortality from colorectal cancer, but comparative effectiveness of these interventions is unknown.<br><br>AIM: To compare aspirin to guaiac FOBT screening with regard to incidence and mortality of colorectal cancer in a network meta-analysis.<br><br>METHODS: We searched Medline, EMBASE and the COCHRANE central register (CENTRAL) for relevant randomised trials identified until 31 October 2015. Randomised trials in average-risk populations that reported colorectal cancer mortality, colorectal cancer incidence, or both, with a minimum follow-up of 2 years, and more than 100 randomised individuals were included. Three investigators independently extracted data. We calculated relative risks [RR with 95% predictive intervals (PrIs)] for the comparison of the interventions by frequentist network meta-analyses.<br><br>RESULTS: The effect of aspirin on colorectal cancer mortality was similar to FOBT (RR 1.03; 95% PrI 0.76-1.39) and flexible sigmoidoscopy (RR 1.16; 95% PrI 0.84-1.60). Aspirin was more effective than FOBT (RR 0.36; 95% PrI 0.22-0.59) and flexible sigmoidoscopy (RR 0.37; 95% PrI 0.22-0.62) in preventing death from or cancer in the proximal colon. Aspirin was equally effective as screening in reducing colorectal cancer incidence, while flexible sigmoidoscopy was superior to FOBT (RR 0.84; 95% PrI 0.72-0.97).<br><br>CONCLUSIONS: Low-dose aspirin seems to be equally effective as flexible sigmoidoscopy or guaiac FOBT screening to reduce colorectal cancer incidence and mortality, and more effective for cancers in the proximal colon. A randomised comparative effectiveness trial of aspirin vs. screening is warranted.}, }
@article {pmid27858930, year = {2017}, author = {Zhang, L and Bahl, MI and Roager, HM and Fonvig, CE and Hellgren, LI and Frandsen, HL and Pedersen, O and Holm, JC and Hansen, T and Licht, TR}, title = {Environmental spread of microbes impacts the development of metabolic phenotypes in mice transplanted with microbial communities from humans.}, journal = {The ISME journal}, volume = {11}, number = {3}, pages = {676-690}, pmid = {27858930}, issn = {1751-7370}, mesh = {Adolescent ; Animals ; Case-Control Studies ; Child ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Insulin Resistance ; Lipids/blood ; Male ; Mice ; Obesity/blood/*microbiology ; }, abstract = {Microbiota transplantation to germ-free animals is a powerful method to study involvement of gut microbes in the aetiology of metabolic syndrome. Owing to large interpersonal variability in gut microbiota, studies with broad coverage of donors are needed to elucidate the establishment of human-derived microbiotas in mice, factors affecting this process and resulting impact on metabolic health. We thus transplanted faecal microbiotas from humans (16 obese and 16 controls) separately into 64 germ-free Swiss Webster mice caged in pairs within four isolators, with two isolators assigned to each phenotype, thereby allowing us to explore the extent of microbial spread between cages in a well-controlled environment. Despite high group-wise similarity between obese and control human microbiotas, transplanted mice in the four isolators developed distinct gut bacterial composition and activity, body mass gain, and insulin resistance. Spread of microbes between cages within isolators interacted with establishment of the transplanted microbiotas in mice, and contributed to the transmission of metabolic phenotypes. Our findings highlight the impact of donor variability and reveal that inter-individual spread of microbes contributes to the development of metabolic traits. This is of major importance for design of animal studies, and indicates that environmental transfer of microbes between individuals may affect host metabolic traits.}, }
@article {pmid27856521, year = {2017}, author = {Hudson, LE and Anderson, SE and Corbett, AH and Lamb, TJ}, title = {Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies.}, journal = {Clinical microbiology reviews}, volume = {30}, number = {1}, pages = {191-231}, pmid = {27856521}, issn = {1098-6618}, support = {DP2 AI112242/AI/NIAID NIH HHS/United States ; T32 AI106699/AI/NIAID NIH HHS/United States ; T32 GM008169/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Clinical Trials as Topic ; Clostridioides difficile/isolation &amp; purification ; Colitis, Ulcerative/*therapy ; Combined Modality Therapy ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Inflammatory Bowel Diseases/therapy ; Probiotics/*administration &amp; dosage ; Research Design ; Treatment Outcome ; }, abstract = {Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases.}, }
@article {pmid27852539, year = {2016}, author = {Heath, RD and Mir, F and Ibdah, JA and Tahan, V}, title = {Microbiome alterations observed in liver diseases present opportunities for potential fecal transplantation.}, journal = {The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology}, volume = {27}, number = {6}, pages = {495-498}, doi = {10.5152/tjg.2016.160011}, pmid = {27852539}, issn = {2148-5607}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Hyperammonemia/microbiology/therapy ; Liver Diseases/*microbiology/*therapy ; }, abstract = {Many disease processes lead to chronic liver disease, however, progress has been made regarding common findings amongst these disease processes that may suggest a path forward for treatment. In particular, common alterations in the intestinal microflora of patients with different etiologies of liver disease may provide a clue as to the pathogenesis of these disorders as well a potential therapy. Data is still scant at this point, however, what is available suggests a promising opportunity for future studies to expand upon what has been demonstrated.}, }
@article {pmid27849232, year = {2016}, author = {Tannuri, AC and Ferreira, MA and Mathias, AL and Tannuri, U}, title = {Long-term evaluation of fecal continence and quality of life in patients operated for anorectal malformations.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {62}, number = {6}, pages = {544-552}, doi = {10.1590/1806-9282.62.06.544}, pmid = {27849232}, issn = {1806-9282}, mesh = {Adolescent ; Anorectal Malformations/complications/psychology/*surgery ; Case-Control Studies ; Child ; Fecal Incontinence/etiology/psychology/*surgery ; Female ; Humans ; Male ; Quality of Life/*psychology ; Surveys and Questionnaires ; Time Factors ; Young Adult ; }, abstract = {INTRODUCTION:: Patients operated for correction of anorectal malformations (ARM) can develop fecal incontinence, constipation, and soiling, with loss in quality of life.<br><br>OBJECTIVE:: To evaluate, through the use of questionnaires, fecal continence, and quality of life of children in the late postoperative follow-up of ARM correction, both high and low. In addition, the levels of fecal continence and quality of life were compared with those of a control group.<br><br>METHOD:: A Fecal Continence Index Questionnaire (ICF) and a Questionnaire for Assessment of Quality of Life Related to Fecal Continence in Children and Adolescents (QQVCFCA) were administered to 63 patients with ARM, aged from 7 to 19 years, whose surgical treatment had been completed for at least 6 months. The patients were compared to a control group of 59 children.<br><br>RESULTS:: In the control group, 25 (42.4%) patients had good continence and 34 (57.6%), normal continence. We found that the quality of life in children with ARM is compromised globally, in all areas and in the ICF questionnaire, compared to controls (p<0.001). There was no difference between patients with high and low defects. Thirty-two (50.8%) patients had other associated anomalies.<br><br>CONCLUSION:: In patients operated for ARM correction, quality of life and ICF were compromised, and there was no difference between patients with high-type and low-type of the disease. In about half the cases there are other associated malformations.}, }
@article {pmid27840368, year = {2017}, author = {Gu, L and Ding, C and Tian, H and Yang, B and Zhang, X and Hua, Y and Zhu, Y and Gong, J and Zhu, W and Li, J and Li, N}, title = {Serial Frozen Fecal Microbiota Transplantation in the Treatment of Chronic Intestinal Pseudo-obstruction: A Preliminary Study.}, journal = {Journal of neurogastroenterology and motility}, volume = {23}, number = {2}, pages = {289-297}, pmid = {27840368}, issn = {2093-0879}, abstract = {BACKGROUND/AIMS: Chronic intestinal pseudo-obstruction (CIPO) is a serious, life-threatening motility disorder that is often related to bacterial overgrowth. Fecal microbiota transplantation (FMT) results in restoration of the normal intestinal microbial community structure. We investigated the efficacy of FMT in the treatment of CIPO patients.<br><br>METHODS: Nine patients (age 18-53 years) with CIPO were enrolled in this prospective, open-label study. Patients received FMT for 6 consecutive days through nasojejunal (NJ) tubes and were followed up for 8 weeks after treatment. We evaluated the rate of clinical improvement and remission, feeding tolerance of enteral nutrition, and CT imaging scores of intestinal obstructions. Lactulose hydrogen breath tests were performed before FMT and 8 weeks after FMT to evaluate for the presence small intestinal bacterial overgrowth (SIBO).<br><br>RESULTS: FMT significantly alleviated bloating symptoms, and symptoms of pain were relieved 2 weeks after FMT. Enteral nutrition administered through a NJ tube after FMT was well-tolerated by 66.7% (6/9) of patients. CT scores of intestinal obstructions were significantly reduced after FMT (P = 0.014). SIBO was eliminated in 71.0% (5/7) of patients.<br><br>CONCLUSIONS: This pilot study demonstrated the safety of using FMT. FMT may relieve symptoms in selected patients with CIPO. FMT may also improve patient tolerance of enteral nutrition delivered via a NJ tube.}, }
@article {pmid27837783, year = {2016}, author = {Pickett-Blakely, O and Newberry, C}, title = {Future Therapies in Obesity.}, journal = {Gastroenterology clinics of North America}, volume = {45}, number = {4}, pages = {705-714}, doi = {10.1016/j.gtc.2016.07.008}, pmid = {27837783}, issn = {1558-1942}, mesh = {Anti-Obesity Agents/therapeutic use ; Bariatric Surgery/methods ; Bioengineering ; Combined Modality Therapy ; Complementary Therapies/methods ; Electric Stimulation Therapy/methods ; Endoscopy, Gastrointestinal/methods ; Fecal Microbiota Transplantation ; Genetic Therapy/methods ; Humans ; Obesity/microbiology/*therapy ; Prebiotics ; Probiotics/therapeutic use ; *Therapies, Investigational ; }, abstract = {Although diet and exercise have been the cornerstone of therapy for obesity, efficacy is suboptimal and short lived. Surgical procedures are durable but invasive therapy for obesity. Supplemental therapies for obesity that are minimally invasive, low risk, and effective are needed. Several therapeutic options are being developed that offer obese patients and their health care providers alternatives to what is currently available.}, }
@article {pmid27837775, year = {2016}, author = {Martinez, KB and Pierre, JF and Chang, EB}, title = {The Gut Microbiota: The Gateway to Improved Metabolism.}, journal = {Gastroenterology clinics of North America}, volume = {45}, number = {4}, pages = {601-614}, pmid = {27837775}, issn = {1558-1942}, support = {F32 DK105728/DK/NIDDK NIH HHS/United States ; P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DK097268/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; }, mesh = {Bariatric Surgery ; Diet ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Obesity/*metabolism/*microbiology/therapy ; Prebiotics ; Probiotics/therapeutic use ; Risk Factors ; }, abstract = {Obesity is an emerging global epidemic with profound challenges to world health care economies and societies. Traditional approaches to fighting obesity have not shown promise in promoting a decline in obesity prevalence. The gut microbiota is becoming widely appreciated for its role in regulating metabolism and thus represents a target for new therapies to combat obesity and associated comorbidities. This article provides an overview of altered microbial community structure in obesity, dietary impact on the gut microbiota, host-microbe interactions contributing to the disease, and improvements in microbial assemblage after bariatric surgery and with therapies targeting the gut microbiome.}, }
@article {pmid27836370, year = {2017}, author = {Tannuri, AC and Ferreira, MA and Mathias, AL and Tannuri, U}, title = {Long-term results of the Duhamel technique are superior to those of the transanal pullthrough: A study of fecal continence and quality of life.}, journal = {Journal of pediatric surgery}, volume = {52}, number = {3}, pages = {449-453}, doi = {10.1016/j.jpedsurg.2016.10.007}, pmid = {27836370}, issn = {1531-5037}, mesh = {Adolescent ; Anal Canal/*surgery ; Case-Control Studies ; Child ; Digestive System Surgical Procedures/*adverse effects ; Fecal Incontinence/etiology/*psychology ; Female ; Follow-Up Studies ; Hirschsprung Disease/*surgery ; Humans ; Male ; Postoperative Complications/*psychology ; *Quality of Life ; Surveys and Questionnaires ; Treatment Outcome ; }, abstract = {BACKGROUND/PURPOSE: The Duhamel and transanal pull-through (TAPT) techniques have been commonly used for the treatment of children with Hirschsprung disease (HD). However, despite adequate treatment, some patients present with fecal incontinence that severely affects the quality of life (QoL) and lead to psychiatric disorders. The objectives of the present study were to evaluate, through previously adapted questionnaires, the incidence of fecal incontinence and the quality of life (QoL) of children with HD who underwent Duhamel or TAPT techniques. In addition, we compared the incidence of fecal incontinence and QoL indices in these patients with those in healthy children.<br><br>MATERIALS/METHODS: The Fecal Continence Index (FCI) questionnaire and the questionnaire for the Assessment of Quality of Life in Children and Adolescents with Fecal Incontinence (AQLCAFI) were used in this study. A series of 41 patients with HD were divided into 2 groups according to the utilized surgical technique: the Duhamel group (20 patients) and the TAPT group (21 patients). The patients were compared with a control group of 59 healthy children.<br><br>RESULTS: In the control group, 25 (42.4%) children had good continence and 34 (57.6%) had normal continence. In contrast, among patients with HD, 4 (9.8%) had poor fecal continence, 11 (26.8%) had fair continence, 18 (43.9%) had good continence, and 8 (19.5%) had normal continence. The QoL of children with HD was globally impaired in all domains of the AQLCAFI as well as in the FCI, when compared with the QoL of healthy children (P=0.001). The comparison between children who underwent surgery with the Duhamel technique and those who underwent surgery with TAPT technique showed similar outcomes according to the FCI. However, the results were inferior in patients who underwent TAPT technique according to the AQLCAFI questionnaire (P=0.003), lifestyle (P=0.006), behavior (P=0.01), depression (P=0.01), and embarrassment (P=0.003).<br><br>CONCLUSION: The QoL and the FCI were impaired in patients who underwent surgery for correction of HD compared with healthy children; however, the impairment in QoL was greater in patients who underwent TAPT technique.<br><br>LEVEL OF EVIDENCE: 2B.}, }
@article {pmid27832684, year = {2016}, author = {Ruggiero, M}, title = {Fecal Microbiota Transplantation and the Brain Microbiota in Neurological Diseases.}, journal = {Clinical endoscopy}, volume = {49}, number = {6}, pages = {579}, pmid = {27832684}, issn = {2234-2400}, }
@article {pmid27827877, year = {2016}, author = {Hartl, J and Wehmeyer, MH and Pischke, S}, title = {Acute Hepatitis E: Two Sides of the Same Coin.}, journal = {Viruses}, volume = {8}, number = {11}, pages = {}, pmid = {27827877}, issn = {1999-4915}, mesh = {Animals ; Antiviral Agents/therapeutic use ; Disease Transmission, Infectious ; Global Health ; Hepatitis E/drug therapy/*epidemiology/*pathology/transmission ; Humans ; Incidence ; Ribavirin/therapeutic use ; Swine ; Treatment Outcome ; Zoonoses/drug therapy/*epidemiology/*pathology/transmission ; }, abstract = {The relevance of acute hepatitis E virus (HEV) infections has been underestimated for a long time. In the past, HEV infection had been interpreted falsely as a disease limited to the tropics until the relevance of autochthonous HEV infections in the Western world became overt. Due to increased awareness, the incidence of diagnosed autochthonous HEV infections (predominantly genotype 3) in industrialized countries has risen within the last decade. The main source of infections in industrialized countries seems to be infected swine meat, while infections with the tropical HEV genotypes 1 and 2 usually are mainly transmitted fecal-orally by contaminated drinking water. In the vast majority of healthy individuals, acute HEV infection is either clinically silent or takes a benign self-limited course. In patients who develop a symptomatic HEV infection, a short prodromal phase with unspecific symptoms is followed by liver specific symptoms like jaundice, itching, uncoloured stool and darkened urine. Importantly, tropical HEV infections may lead to acute liver failure, especially in pregnant women, while autochthonous HEV infections may lead to acute-on-chronic liver failure in patients with underlying liver diseases. Immunosuppressed individuals, such as transplant recipients or human immunodeficiency virus (HIV)-infected patients, are at risk for developing chronic hepatitis E, which may lead to liver fibrosis and cirrhosis in the long term. Importantly, specific treatment options for hepatitis E are not approved by the regulation authorities, but off-label ribavirin treatment seems to be effective in the treatment of chronic HEV-infection and may reduce the disease severity in patients suffering from acute liver failure.}, }
@article {pmid27822878, year = {2016}, author = {Perbal, B}, title = {To flush or not to flush … that is a question.}, journal = {Journal of cell communication and signaling}, volume = {10}, number = {4}, pages = {337-340}, pmid = {27822878}, issn = {1873-9601}, abstract = {The human gut microflora has drawn a lot of attention as a potent therapeutic tool for many decades. More recently, efforts have been developed to devise efficient ways of complementing or replacing deficient intestinal microflora associated with intestinal diseases that are resistant to conventional medical treatments. Aside from the medical and industrial applications that emerged from the use of gut microbiota, the complex constitution of this ecosystem raises fascinating questions regarding host-cell communication and host response mechanisms to the ever changing environment. This brief comment also points to questions raised by some unexpected applications that have recently emerged from this field.}, }
@article {pmid27822485, year = {2016}, author = {Hecker, MT and Obrenovich, ME and Cadnum, JL and Jencson, AL and Jain, AK and Ho, E and Donskey, CJ}, title = {Fecal Microbiota Transplantation by Freeze-Dried Oral Capsules for Recurrent Clostridium difficile Infection.}, journal = {Open forum infectious diseases}, volume = {3}, number = {2}, pages = {ofw091}, pmid = {27822485}, issn = {2328-8957}, }
@article {pmid27821277, year = {2016}, author = {Kosulin, K and Dworzak, S and Lawitschka, A and Matthes-Leodolter, S and Lion, T}, title = {Comparison of different approaches to quantitative adenovirus detection in stool specimens of hematopoietic stem cell transplant recipients.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {85}, number = {}, pages = {31-36}, doi = {10.1016/j.jcv.2016.10.021}, pmid = {27821277}, issn = {1873-5967}, mesh = {Adenovirus Infections, Human/*virology ; Adenoviruses, Human/*isolation &amp; purification ; DNA, Viral/analysis/isolation &amp; purification ; Feces/*virology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Real-Time Polymerase Chain Reaction ; *Transplant Recipients ; Viral Load/*methods ; }, abstract = {BACKGROUND: Adenoviruses almost invariably proliferate in the gastrointestinal tract prior to dissemination, and critical threshold concentrations in stool correlate with the risk of viremia. Monitoring of adenovirus loads in stool may therefore be important for timely initiation of treatment in order to prevent invasive infection.<br><br>OBJECTIVES: Comparison of a manual DNA extraction kit in combination with a validated in-house PCR assay with automated extraction on the NucliSENS-EasyMAG device coupled with the Adenovirus R-gene kit (bioM&#xe9;rieux) for quantitative adenovirus analysis in stool samples.<br><br>STUDY DESIGN: Stool specimens spiked with adenovirus concentrations in a range from 10E2-10E11 copies/g and 32 adenovirus-positive clinical stool specimens from pediatric stem cell transplant recipients were tested along with appropriate negative controls.<br><br>RESULTS: Quantitative analysis of viral load in adenovirus-positive stool specimens revealed a median difference of 0.5 logs (range 0.1-2.2) between the detection systems tested and a difference of 0.3 logs (range 0.0-1.7) when the comparison was restricted to the PCR assays only. Spiking experiments showed a detection limit of 10[2]-10[3]adenovirus copies/g stool revealing a somewhat higher sensitivity offered by the automated extraction. The dynamic range of accurate quantitative analysis by both systems investigated was between 10[3] and 10[8] virus copies/g.<br><br>CONCLUSIONS: The differences in quantitative analysis of adenovirus copy numbers between the systems tested were primarily attributable to the DNA extraction method used, while the qPCR assays revealed a high level of concordance. Both systems showed adequate performance for detection and monitoring of adenoviral load in stool specimens.}, }
@article {pmid27817758, year = {2017}, author = {Rodrigues, R and Barber, GE and Ananthakrishnan, AN}, title = {A Comprehensive Study of Costs Associated With Recurrent Clostridium difficile Infection.}, journal = {Infection control and hospital epidemiology}, volume = {38}, number = {2}, pages = {196-202}, doi = {10.1017/ice.2016.246}, pmid = {27817758}, issn = {1559-6834}, support = {K23 DK097142/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Boston/epidemiology ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*economics/*epidemiology/therapy ; Colectomy/adverse effects ; Cross Infection/*economics/*epidemiology/therapy ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Health Care Costs/*statistics &amp; numerical data ; Humans ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Recurrence ; Time Factors ; Young Adult ; }, abstract = {BACKGROUND Clostridium difficile infection (CDI) is the most common healthcare-associated infection and is associated with considerable morbidity. Recurrent CDI is a key contributing factor to this morbidity. Despite an estimated 83,000 recurrences annually in the United States, there are few accurate estimates of costs associated with recurrent CDI. OBJECTIVE We performed this study (1) to identify the health consequences of recurrent CDI including need for repeat hospitalization, intensive care unit (ICU) stay, and surgery; (2) to determine costs associated with recurrent CDI and identify determinants of such costs; and (3) to compare the outcomes and costs of recurrent CDI to those who develop reinfection. METHODS We identified all patients with confirmed recurrent CDI between January to December 2013 at a single referral center. Healthcare burden associated with recurrence including diagnostic testing, pharmacologic treatment, and inpatient and outpatient healthcare visits were identified in the 12 months following the first recurrence. Total healthcare costs were calculated, and the predictors of high healthcare utilization were identified. RESULTS Our study population included 98 patients with recurrent CDI. The median interval between the initial infection and recurrence was 37 days. The mean age of the cohort was 67 years, two-thirds were women (62%), and the mean Charlson index was 8.6. During the year following the first recurrence of CDI, each patient underwent a mean of 4.4 stool C. difficile toxin tests and received a mean of 2.5 prescriptions for oral vancomycin (range, 0-6). Most patients (84%) with recurrence had a CDI-related hospitalization, and 6% underwent colectomy. The mean total CDI-associated cost was $34,104 per patient, with hospitalization costs accounting for 68%, surgery 20%, and drug treatment 8% of this cost, respectively. Extrapolating to the United States overall, we estimate an annual cost of $2.8 billion related to recurrent CDI. CONCLUSION Recurrent CDI is associated with considerable morbidity and cost. Infect Control Hosp Epidemiol 2017;38:196-202.}, }
@article {pmid27816755, year = {2017}, author = {Philips, CA and Pande, A and Shasthry, SM and Jamwal, KD and Khillan, V and Chandel, SS and Kumar, G and Sharma, MK and Maiwall, R and Jindal, A and Choudhary, A and Hussain, MS and Sharma, S and Sarin, SK}, title = {Healthy Donor Fecal Microbiota Transplantation in Steroid-Ineligible Severe Alcoholic Hepatitis: A Pilot Study.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {15}, number = {4}, pages = {600-602}, doi = {10.1016/j.cgh.2016.10.029}, pmid = {27816755}, issn = {1542-7714}, mesh = {Dysbiosis/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; *Gastrointestinal Microbiome ; Hepatitis, Alcoholic/*complications ; Humans ; Male ; Pilot Projects ; Treatment Outcome ; }, }
@article {pmid27809778, year = {2016}, author = {Wei, Y and Gong, J and Zhu, W and Tian, H and Ding, C and Gu, L and Li, N and Li, J}, title = {Pectin enhances the effect of fecal microbiota transplantation in ulcerative colitis by delaying the loss of diversity of gut flora.}, journal = {BMC microbiology}, volume = {16}, number = {1}, pages = {255}, pmid = {27809778}, issn = {1471-2180}, mesh = {Adolescent ; Adult ; Aged ; Colitis, Ulcerative/*drug therapy/*therapy ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Male ; Microbiota/drug effects ; Middle Aged ; Pectins/*administration &amp; dosage ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) induces remission in ulcerative colitis (UC). However, the treatment effect of FMT diminishes over time. Maintaining the diversity of the gut flora for long periods may improve the effects of FMT in UC. Pectin, which can be fermented by gut microbiota into short-chain fatty acids, is postulated to shape the composition and maintain the balance of gut microbiota following transplantation. This study investigated whether pectin could enhance the effects of FMT in UC patients.<br><br>RESULTS: Three FMT patients and four FMTP patients achieved the primary outcome. The Mayo scores of the FMTP group were lower than those of the FMT group at weeks 4 and 12 (P&#x2009;=&#x2009;0.042 and P&#x2009;=&#x2009;0.042, respectively). There were no differences in the diversity of the gut flora between the two groups at weeks 4 and 12; however, the composition of the gut flora of the FMTP group was more similar than the FMT group to that of the donor at all-time points post-treatment.<br><br>CONCLUSIONS: Pectin decreased the Mayo score by preserving the diversity of the gut flora following FMT for UC.<br><br>TRIAL REGISTRATION: Current Controlled Trial NCT02016469 . Registered 10 November 2013.}, }
@article {pmid27762148, year = {2017}, author = {Bandera, A and Colella, E and Rizzardini, G and Gori, A and Clerici, M}, title = {Strategies to limit immune-activation in HIV patients.}, journal = {Expert review of anti-infective therapy}, volume = {15}, number = {1}, pages = {43-54}, doi = {10.1080/14787210.2017.1250624}, pmid = {27762148}, issn = {1744-8336}, mesh = {Animals ; Anti-Inflammatory Agents/administration &amp; dosage/therapeutic use ; Anti-Retroviral Agents/administration &amp; dosage/adverse effects/*therapeutic use ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/cytology/immunology ; Fecal Microbiota Transplantation ; HIV Infections/blood/*drug therapy/*immunology/virology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration &amp; dosage/therapeutic use ; Immune System Phenomena/*drug effects ; Lymphocyte Activation/drug effects/immunology ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage/therapeutic use ; Viral Load ; Virus Replication/*drug effects ; }, abstract = {Antiretroviral treatment of HIV infection reduces, but does not eliminate, viral replication and down modulates immune activation. The persistence of low level HIV replication in the host, nevertheless, drives a smouldering degree of immune activation that is observed throughout the natural history of disease and is the main driving force sustaining morbidity and mortality. Areas covered: Early start of antiretroviral therapy (ART) and intensive management of behavioural risk factors are possible but, at best, marginally successful ways to manage immune activation. We review alternative, possible strategies to reduce immune activation in HIV infection including timing of ART initiation and ART intensification to reduce HIV residual viremia; switch of ART to newer molecules with reduced toxicity; use of anti inflammatory/immunomodulatory agents and, finally, interventions aimed at modifying the composition of the microbiota. Expert commentary: Current therapeutic strategies to limit immune activation are only marginally successful. Because HIV eradication is currently impossible, intensive studies are needed to determine if and how immune activation can be silenced in HIV infection.}, }
@article {pmid27712927, year = {2016}, author = {García-Fernández, S and Morosini, MI and Cobo, M and Foruny, JR and López-Sanromán, A and Cobo, J and Romero, J and Cantón, R and Del Campo, R}, title = {Gut eradication of VIM-1 producing ST9 Klebsiella oxytoca after fecal microbiota transplantation for diarrhea caused by a Clostridium difficile hypervirulent R027 strain.}, journal = {Diagnostic microbiology and infectious disease}, volume = {86}, number = {4}, pages = {470-471}, doi = {10.1016/j.diagmicrobio.2016.09.004}, pmid = {27712927}, issn = {1879-0070}, mesh = {Carrier State/*therapy ; Clostridioides difficile/*isolation &amp; purification ; Diarrhea ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Tract/microbiology ; Humans ; Klebsiella Infections/*therapy ; Klebsiella oxytoca/enzymology/*isolation &amp; purification ; beta-Lactamases/metabolism ; }, abstract = {We report the fecal carriage eradication of a VIM-1-producing ST9 Klebsiella oxytoca strain in a pluripathological 84-year-old woman after fecal microbiota transplantation to control relapsing R027 hypervirulent Clostridium difficile infections. The donor was her son, in which the absence of fecal carbapenemase-producing bacteria was corroborated.}, }
@article {pmid27377777, year = {2016}, author = {Zhang, X and Chen, Y and Gu, S and Zheng, B and Lv, T and Lou, Y and Jin, J}, title = {A case of multiple recurrence of Clostridium difficile infection with severe hematochezia in an immunocompromised host.}, journal = {Anaerobe}, volume = {42}, number = {}, pages = {31-32}, doi = {10.1016/j.anaerobe.2016.06.010}, pmid = {27377777}, issn = {1095-8274}, mesh = {Clostridioides difficile/genetics/*isolation &amp; purification ; Clostridium Infections/diagnosis/*immunology/microbiology ; Diarrhea/diagnosis/*immunology/microbiology ; Feces/microbiology ; Gastrointestinal Hemorrhage/diagnosis/*immunology/microbiology ; Hematopoietic Stem Cell Transplantation ; Humans ; *Immunocompromised Host ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology/pathology/therapy ; Recurrence ; Young Adult ; }, abstract = {Clostridium difficile infection (CDI) is increasing in incidence and severity. Clinically, diarrhea frequently occurs, but severe hematochezia is rarely seen with CDI. We describe here a hematopoietic stem cell transplantation (HSCT) recipient who experienced life-threatening gastrointestinal bleeding due to severe CDI. Subsequent stool surveillance and molecular typing observed the patient who had two episodes of recurrence with a new strain of C. difficile distinct from the initial infection. We analyze C. difficile strains obtained from the patient, and also discuss the diagnosis and treatment of this case.}, }
@article {pmid27166127, year = {2016}, author = {Kahn, SA and Rubin, DT}, title = {When Subjects Violate the Research Covenant: Lessons Learned from a Failed Clinical Trial of Fecal Microbiota Transplantation.}, journal = {The American journal of gastroenterology}, volume = {111}, number = {11}, pages = {1508-1510}, pmid = {27166127}, issn = {1572-0241}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; }, mesh = {*Clinical Trials as Topic ; Colitis, Ulcerative/*therapy ; Colonoscopy ; *Deception ; Ethics, Research ; *Fecal Microbiota Transplantation ; Humans ; *Patient Dropouts ; *Research Subjects ; }, }
@article {pmid27800166, year = {2016}, author = {Nwokoro, E and Leach, R and Årdal, C and Baraldi, E and Ryan, K and Plahte, J}, title = {An assessment of the future impact of alternative technologies on antibiotics markets.}, journal = {Journal of pharmaceutical policy and practice}, volume = {9}, number = {}, pages = {34}, pmid = {27800166}, issn = {2052-3211}, abstract = {BACKGROUND: The increasing threat of antimicrobial resistance combined with the paucity of new classes of antibiotics represents a serious public health challenge. New treatment technologies could, in theory, have a significant impact on the future use of traditional antibiotics, be it by facilitating rational and responsible use or by product substitution in the existing antibiotics markets, including by reducing the incidence of bacterial infections through preventative approaches. The aim of this paper is to assess the potential of alternative technologies in reducing clinical use of and demand for antibiotics, and to briefly indicate which segments of the antibiotics market that might be impacted by these technologies.<br><br>METHODS: An initial mapping exercise to identify the alternative technologies was followed by a review of relevant published and grey literature (n&#x2009;=&#x2009;52). We also carried out stakeholder engagement activities by a round-table discussion with infectious disease specialists and a multi-criteria decision analysis exercise with pharmaceutical industry experts.<br><br>RESULTS: Ten alternative technologies were identified and analyzed for their potential impact on the antibiotics market. Of these, rapid point-of-care diagnostics, vaccines, fecal microbiota transplantation, and probiotics were considered to have a "high" or "medium" potential impact over a 10-20 year horizon. Therapeutic antibodies, antibiotic biomaterials, bacteriophages, antimicrobial nanoparticles, antimicrobial peptides, and anti-virulence materials were rated as having "low" potential impact.<br><br>CONCLUSION: Despite the apparent potential of the most promising alternative technologies to reduce demand, that reduction will likely only happen in limited segments of the antibiotics market or, in the case of preventing community acquired streptococcal infections by vaccination, in a low-price generics market segment. Thus, alternative technologies are not expected to represent any disincentive to antibiotics developers. Finally, it is unlikely that alternative technologies will displace the need for new classes, and sub-classes, of antibiotics in the short and medium terms.}, }
@article {pmid27799307, year = {2016}, author = {Selvanantham, T and Lin, Q and Guo, CX and Surendra, A and Fieve, S and Escalante, NK and Guttman, DS and Streutker, CJ and Robertson, SJ and Philpott, DJ and Mallevaey, T}, title = {NKT Cell-Deficient Mice Harbor an Altered Microbiota That Fuels Intestinal Inflammation during Chemically Induced Colitis.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {197}, number = {11}, pages = {4464-4472}, doi = {10.4049/jimmunol.1601410}, pmid = {27799307}, issn = {1550-6606}, support = {//CIHR/Canada ; }, mesh = {Animals ; Colitis/chemically induced/*immunology/*microbiology/pathology ; Dextran Sulfate/toxicity ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Inflammation/chemically induced/immunology/microbiology/pathology ; *Lymphocyte Activation ; Mice ; Mice, Knockout ; Natural Killer T-Cells/*immunology/pathology ; Prevotella/immunology ; Th2 Cells/immunology/pathology ; }, abstract = {NKT cells are unconventional T cells that respond to self and microbe-derived lipid and glycolipid Ags presented by the CD1d molecule. Invariant NKT (iNKT) cells influence immune responses in numerous diseases. Although only a few studies have examined their role during intestinal inflammation, it appears that iNKT cells protect from Th1-mediated inflammation but exacerbate Th2-mediated inflammation. Studies using iNKT cell-deficient mice and chemically induced dextran sodium sulfate (DSS) colitis have led to inconsistent results. In this study, we show that CD1d-deficient mice, which lack all NKT cells, harbor an altered intestinal microbiota that is associated with exacerbated intestinal inflammation at steady-state and following DSS treatment. This altered microbiota, characterized by increased abundance of the bacterial phyla Proteobacteria, Deferribacteres, and TM7, among which the mucin-eating Mucispirillum, as well as members of the genus Prevotella and segmented filamentous bacteria, was transmissible upon fecal transplant, along with the procolitogenic phenotype. Our results also demonstrate that this proinflammatory microbiota influences iNKT cell function upon activation during DSS colitis. Collectively, alterations of the microbiota have a major influence on colitis outcome and therefore have to be accounted for in such experimental settings and in studies focusing on iNKT cells.}, }
@article {pmid27799253, year = {2017}, author = {Santisteban, MM and Qi, Y and Zubcevic, J and Kim, S and Yang, T and Shenoy, V and Cole-Jeffrey, CT and Lobaton, GO and Stewart, DC and Rubiano, A and Simmons, CS and Garcia-Pereira, F and Johnson, RD and Pepine, CJ and Raizada, MK}, title = {Hypertension-Linked Pathophysiological Alterations in the Gut.}, journal = {Circulation research}, volume = {120}, number = {2}, pages = {312-323}, pmid = {27799253}, issn = {1524-4571}, support = {R01 HL033610/HL/NHLBI NIH HHS/United States ; R01 HL132448/HL/NHLBI NIH HHS/United States ; R37 HL033610/HL/NHLBI NIH HHS/United States ; }, mesh = {Angiotensin II/toxicity ; Angiotensin-Converting Enzyme Inhibitors/pharmacology/therapeutic use ; Animals ; Gastrointestinal Microbiome/drug effects/*physiology ; Hypertension/drug therapy/*metabolism/*physiopathology ; Intestinal Mucosa/drug effects/*metabolism/*physiopathology ; Male ; Permeability/drug effects ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Rats, Sprague-Dawley ; Rats, Wistar ; }, abstract = {RATIONALE: Sympathetic nervous system control of inflammation plays a central role in hypertension. The gut receives significant sympathetic innervation, is densely populated with a diverse microbial ecosystem, and contains immune cells that greatly impact overall inflammatory homeostasis. Despite this uniqueness, little is known about the involvement of the gut in hypertension.<br><br>OBJECTIVE: Test the hypothesis that increased sympathetic drive to the gut is associated with increased gut wall permeability, increased inflammatory status, and microbial dysbiosis and that these gut pathological changes are linked to hypertension.<br><br>METHODS AND RESULTS: Gut epithelial integrity and wall pathology were examined in spontaneously hypertensive rat and chronic angiotensin II infusion rat models. The increase in blood pressure in spontaneously hypertensive rat was associated with gut pathology that included increased intestinal permeability and decreased tight junction proteins. These changes in gut pathology in hypertension were associated with alterations in microbial communities relevant in blood pressure control. We also observed enhanced gut-neuronal communication in hypertension originating from paraventricular nucleus of the hypothalamus and presenting as increased sympathetic drive to the gut. Finally, angiotensin-converting enzyme inhibition (captopril) normalized blood pressure and was associated with reversal of gut pathology.<br><br>CONCLUSIONS: A dysfunctional sympathetic-gut communication is associated with gut pathology, dysbiosis, and inflammation and plays a key role in hypertension. Thus, targeting of gut microbiota by innovative probiotics, antibiotics, and fecal transplant, in combination with the current pharmacotherapy, may be a novel strategy for hypertension treatment.}, }
@article {pmid27795585, year = {2016}, author = {Davis, CD}, title = {The Gut Microbiome and Its Role in Obesity.}, journal = {Nutrition today}, volume = {51}, number = {4}, pages = {167-174}, pmid = {27795585}, issn = {0029-666X}, support = {Z99 OD999999//Intramural NIH HHS/United States ; }, abstract = {The human body is host to a vast number of microbes, including bacterial, fungal and protozoal microoganisms, which together constitute our microbiota. Evidence is emerging that the intestinal microbiome is intrinsically linked with overall health, including obesity risk. Obesity and obesity-related metabolic disorders are characterized by specific alterations in the composition and function of the human gut microbiome. Mechanistic studies have indicated that the gastrointestinal microbiota can influence both sides of the energy balance equation; namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Moreover, its composition is not fixed and can be influenced by several dietary components. This fact raises the attractive possibility that manipulating the gut microbiota could facilitate weight loss or prevent obesity in humans. Emerging as possible strategies for obesity prevention and/or treatment are targeting the microbiota, in order to restore or modulate its composition through the consumption of live bacteria (probiotics), nondigestible or limited digestible food constituents such as oligosaccharides (prebiotics), or both (synbiotics), or even fecal transplants.}, }
@article {pmid27548329, year = {2016}, author = {Hohmann, EL}, title = {Are Microbial Politics Local?.}, journal = {Annals of internal medicine}, volume = {165}, number = {9}, pages = {667-668}, doi = {10.7326/M16-1784}, pmid = {27548329}, issn = {1539-3704}, mesh = {Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Reproducibility of Results ; }, }
@article {pmid27547925, year = {2016}, author = {Kelly, CR and Khoruts, A and Staley, C and Sadowsky, MJ and Abd, M and Alani, M and Bakow, B and Curran, P and McKenney, J and Tisch, A and Reinert, SE and Machan, JT and Brandt, LJ}, title = {Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial.}, journal = {Annals of internal medicine}, volume = {165}, number = {9}, pages = {609-616}, pmid = {27547925}, issn = {1539-3704}, support = {R21 AI114722/AI/NIAID NIH HHS/United States ; }, mesh = {*Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Colonoscopy ; Diarrhea/microbiology/*therapy ; Double-Blind Method ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Humans ; Intention to Treat Analysis ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: To date, evidence for the efficacy of fecal microbiota transplantation (FMT) in recurrent Clostridium difficile infection (CDI) has been limited to case series and open-label clinical trials.<br><br>OBJECTIVE: To determine the efficacy and safety of FMT for treatment of recurrent CDI.<br><br>DESIGN: Randomized, controlled, double-blind clinical trial. (ClinicalTrials.gov: NCT01703494).<br><br>SETTING: Two academic medical centers.<br><br>PATIENTS: 46 patients who had 3 or more recurrences of CDI and received a full course of vancomycin for their most recent acute episode.<br><br>INTERVENTION: Fecal microbiota transplantation with donor stool (heterologous) or patient's own stool (autologous) administered by colonoscopy.<br><br>MEASUREMENTS: The primary end point was resolution of diarrhea without the need for further anti-CDI therapy during the 8-week follow-up. Safety data were compared between treatment groups via review of adverse events (AEs), serious AEs (SAEs), and new medical conditions for 6 months after FMT. Fecal microbiota analyses were performed on patients' stool before and after FMT and also on donors' stool.<br><br>RESULTS: In the intention-to-treat analysis, 20 of 22 patients (90.9%) in the donor FMT group achieved clinical cure compared with 15 of 24 (62.5%) in the autologous FMT group (P&#xa0;= 0.042). Resolution after autologous FMT differed by site (9 of 10 vs. 6 of 14 [P&#xa0;= 0.033]). All 9 patients who developed recurrent CDI after autologous FMT were free of further CDI after subsequent donor FMT. There were no SAEs related to FMT. Donor FMT restored gut bacterial community diversity and composition to resemble that of healthy donors.<br><br>LIMITATION: The study included only patients who had 3 or more recurrences and excluded those who were immunocompromised and aged 75 years or older.<br><br>CONCLUSION: Donor stool administered via colonoscopy seemed safe and was more efficacious than autologous FMT in preventing further CDI episodes.<br><br>PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases.}, }
@article {pmid27632248, year = {2016}, author = {Lum, SH and Turner, A and Guiver, M and Bonney, D and Martland, T and Davies, E and Newbould, M and Brown, J and Morfopoulou, S and Breuer, J and Wynn, R}, title = {An emerging opportunistic infection: fatal astrovirus (VA1/HMO-C) encephalitis in a pediatric stem cell transplant recipient.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {18}, number = {6}, pages = {960-964}, doi = {10.1111/tid.12607}, pmid = {27632248}, issn = {1399-3062}, mesh = {Astroviridae Infections/*virology ; Biopsy ; Bone Marrow Transplantation/*adverse effects ; Brain/diagnostic imaging/pathology ; Chromosomes, Human, Pair 10/genetics ; Chromosomes, Human, Pair 11/genetics ; Diarrhea/etiology ; Encephalitis, Viral/cerebrospinal fluid/diagnostic imaging/pathology/*virology ; Enteritis/complications/virology ; Fatal Outcome ; Feces/virology ; Female ; Graft vs Host Disease/drug therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/administration &amp; dosage/*adverse effects/therapeutic use ; Infant ; Leukemia, Myeloid, Acute/drug therapy/genetics/*surgery ; Magnetic Resonance Imaging ; Mamastrovirus/*isolation &amp; purification ; Opportunistic Infections/*virology ; RNA, Viral/isolation &amp; purification ; Sequence Analysis, RNA ; Translocation, Genetic ; Transplantation Conditioning/*adverse effects ; }, abstract = {Neuroinvasive astrovirus (VA1-HMO-C) is an emerging life-threatening infection in immunocompromised hosts. We describe an 8-month-old child who died of VA1/HMO-C encephalitis following bone marrow transplantation. The diagnosis was only made post-mortem using RNA deep sequencing of the brain. Repeat analysis of the post-mortem brain tissue using polymerase chain reaction specific primers for VA1/HMO-C was positive. Astrovirus VA1/HMO-C should be included in the evaluation of patients with similar encephalitis.}, }
@article {pmid27282271, year = {2016}, author = {Ni, X and Fan, S and Zhang, Y and Wang, Z and Ding, L and Li, Y and Li, J}, title = {Coordinated Hospital-Home Fecal Microbiota Transplantation via Percutaneous Endoscopic Cecostomy for Recurrent Steroid-Dependent Ulcerative Colitis.}, journal = {Gut and liver}, volume = {10}, number = {6}, pages = {975-980}, pmid = {27282271}, issn = {2005-1212}, mesh = {Cecostomy/*methods ; Colitis, Ulcerative/drug therapy/*surgery ; Colonoscopy ; Combined Modality Therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Male ; Recurrence ; Steroids/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {Since its introduction as an alternative intestinal microbiota alteration approach, fecal microbiota transplantation (FMT) has been increasingly used as a treatment of choice for patients with ulcerative colitis (UC), but no reports exist regarding FMT via percutaneous endoscopic cecostomy (PEC). This report describes the case of a 24-year-old man with a 7-year history of recurrent, steroid-dependent UC. He received FMT via PEC once per day for 1 month in the hospital. After the remission of gastrointestinal symptoms, he was discharged from the hospital and continued FMT via PEC twice per week for 3 months at home. The frequency of stools decreased, and the characteristics of stools improved soon thereafter. Enteral nutrition was regained after 1 week, and an oral diet was begun 1 month later. Two months after the FMT end point, the patient resumed a normal diet, with formed soft stools once per day. The follow-up colonoscopy showed normal mucus membranes; then, the PEC set was removed. On the subsequent 12 months follow-up, the patient resumed orthobiosis without any gastrointestinal discomfort and returned to work. This case emphasizes that FMT via PEC can not only induce remission but also shorten the duration of hospitalization and reduce the medical costs; therefore, this approach should be considered an alternative option for patients with UC.}, }
@article {pmid27753689, year = {2016}, author = {Martin, J and Wilcox, M}, title = {New and emerging therapies for Clostridium difficile infection.}, journal = {Current opinion in infectious diseases}, volume = {29}, number = {6}, pages = {546-554}, doi = {10.1097/QCO.0000000000000320}, pmid = {27753689}, issn = {1473-6527}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/therapeutic use ; Benzimidazoles/therapeutic use ; Broadly Neutralizing Antibodies ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation ; Humans ; Lipopeptides/therapeutic use ; Oxazolidinones/therapeutic use ; Peptides, Cyclic/therapeutic use ; Pyridines/therapeutic use ; Recurrence ; Secondary Prevention/methods ; }, abstract = {PURPOSE OF REVIEW: Clostridium difficile infection has attained high prominence given its prevalence and impacts on patients and healthcare institutions. Multiple new approaches to the prevention and treatment of C. difficile infection (CDI) are undergoing clinical trials.<br><br>RECENT FINDINGS: Bezlotoxumab is a monoclonal antibody against toxin B that has successfully completed phase III studies, demonstrating a significant reduction in recurrent CDI when given with standard of care antibiotics. Antibiotics under development include cadazolid and ridinilazole, whereas surotomycin has had disappointing phase III results. Multiple live biotherapeutics are being developed, including freeze thawed and encapsulated versions of faecal microbiota transplantation to improve the practicality of treating patients with recurrent CDI. Alternatives to faecal microbiota transplantation, that aim to improve safety, including a microbial suspension, RBX2660, and a complex spore formulation, SER-109, have progressed to phase II studies. A nontoxigenic C. difficile strain has also shown promise to prevent recurrent CDI. In addition, three C. difficile vaccines have progressed to phase II/III clinical trials.<br><br>SUMMARY: The diverse approaches to treating and preventing CDI offer substantial promise that new treatment options will soon emerge, particular ones that reduce the risk of recurrences.}, }
@article {pmid27774001, year = {2016}, author = {Slattery, J and MacFabe, DF and Frye, RE}, title = {The Significance of the Enteric Microbiome on the Development of Childhood Disease: A Review of Prebiotic and Probiotic Therapies in Disorders of Childhood.}, journal = {Clinical medicine insights. Pediatrics}, volume = {10}, number = {}, pages = {91-107}, pmid = {27774001}, issn = {1179-5565}, abstract = {Recent studies have highlighted the fact that the enteric microbiome, the trillions of microbes that inhabit the human digestive tract, has a significant effect on health and disease. Methods for manipulating the enteric microbiome, particularly through probiotics and microbial ecosystem transplantation, have undergone some study in clinical trials. We review some of the evidence for microbiome alteration in relation to childhood disease and discuss the clinical trials that have examined the manipulation of the microbiome in an effort to prevent or treat childhood disease with a primary focus on probiotics, prebiotics, and/or synbiotics (ie, probiotics + prebiotics). Studies show that alterations in the microbiome may be a consequence of events occurring during infancy and/or childhood such as prematurity, C-sections, and nosocomial infections. In addition, certain childhood diseases have been associated with microbiome alterations, namely necrotizing enterocolitis, infantile colic, asthma, atopic disease, gastrointestinal disease, diabetes, malnutrition, mood/anxiety disorders, and autism spectrum disorders. Treatment studies suggest that probiotics are potentially protective against the development of some of these diseases. Timing and duration of treatment, the optimal probiotic strain(s), and factors that may alter the composition and function of the microbiome are still in need of further research. Other treatments such as prebiotics, fecal microbial transplantation, and antibiotics have limited evidence. Future translational work, in vitro models, long-term and follow-up studies, and guidelines for the composition and viability of probiotic and microbial therapies need to be developed. Overall, there is promising evidence that manipulating the microbiome with probiotics early in life can help prevent or reduce the severity of some childhood diseases, but further research is needed to elucidate biological mechanisms and determine optimal treatments.}, }
@article {pmid27575658, year = {2016}, author = {Link, A and Lachmund, T and Schulz, C and Weigt, J and Malfertheiner, P}, title = {Endoscopic peroral jejunal fecal microbiota transplantation.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {48}, number = {11}, pages = {1336-1339}, doi = {10.1016/j.dld.2016.08.110}, pmid = {27575658}, issn = {1878-3562}, mesh = {Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; *Endoscopy ; Fecal Microbiota Transplantation/*methods ; Female ; Germany ; Humans ; Jejunum/*microbiology ; Male ; Prospective Studies ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a valuable treatment modality for recurrent Clostridium difficile (C. difficile) colitis. Multiple questions including the best delivery route and volume remain unanswered. Here, we report a case series of high-volume FMT using endoscopic jejunal application route.<br><br>METHODS: In prospective observational study, FMT was performed using fresh specimen from healthy unrelated donors to the patients with recurrent or refractory C. difficile colitis. Selection of the route was based on the patient's preferences. Specimens of at least 50g were dissolved in 500ml of electrolyte solution and administered using endoscope directly in jejunum.<br><br>RESULTS: All procedures led to cure of C. difficile colitis. With exception of one case the procedure was well tolerated. In two cases, we observed FMT-reflux into the stomach despite deep jejunal application and in single case the FMT-reflux led to tracheal aspiration and severe pneumonia.<br><br>CONCLUSIONS: High-volume FMT via endoscopic jejunal route is an effective treatment option that is well tolerated and easy to perform. Nevertheless, aspiration is potential life-threatening event that needs to be kept in mind during the FMT-procedure.}, }
@article {pmid27769810, year = {2017}, author = {Sartor, RB and Wu, GD}, title = {Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches.}, journal = {Gastroenterology}, volume = {152}, number = {2}, pages = {327-339.e4}, pmid = {27769810}, issn = {1528-0012}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/genetics/metabolism ; Colitis, Ulcerative/metabolism/microbiology ; Crohn Disease/metabolism/microbiology ; Dysbiosis/metabolism/*microbiology ; Fungi/genetics/metabolism ; Gastrointestinal Microbiome/*genetics ; Humans ; Inflammatory Bowel Diseases/metabolism/*microbiology ; Metabolome ; Metagenome ; Pouchitis/metabolism/microbiology ; Viruses/genetics/metabolism ; }, abstract = {Intestinal microbiota are involved in the pathogenesis of Crohn's disease, ulcerative colitis, and pouchitis. We review the mechanisms by which these gut bacteria, fungi, and viruses mediate mucosal homeostasis via their composite genes (metagenome) and metabolic products (metabolome). We explain how alterations to their profiles and functions under conditions of dysbiosis contribute to inflammation and effector immune responses that mediate inflammatory bowel diseases (IBD) in humans and enterocolitis in mice. It could be possible to engineer the intestinal environment by modifying the microbiota community structure or function to treat patients with IBD-either with individual agents, via dietary management, or as adjuncts to immunosuppressive drugs. We summarize the latest information on therapeutic use of fecal microbial transplantation and propose improved strategies to selectively normalize the dysbiotic microbiome in personalized approaches to treatment.}, }
@article {pmid27619640, year = {2016}, author = {Young, VB}, title = {Therapeutic manipulation of the microbiota: past, present, and considerations for the future.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {22}, number = {11}, pages = {905-909}, pmid = {27619640}, issn = {1469-0691}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Clostridioides difficile ; Clostridium Infections/*therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation/history/*methods ; Feces/microbiology ; History, 20th Century ; Humans ; Inflammatory Bowel Diseases/*therapy ; *Microbiota ; }, abstract = {BACKGROUND: The growing appreciation of the potential role of indigenous microbiota in disease has resulted in a concomitant interest in manipulating the microbiome for therapeutic effect. The most successful example of microbiota manipulation for treatment of a disease is in recurrent infection with the bacterial pathogen Clostridium difficile.<br><br>AIMS: This review provides historic perspectives on development of microbiota transplantation and reviews evidence for its use in recurrent C.&#xa0;difficile infection.<br><br>SOURCES: A PubMed search of the terms ([fecal transplant OR fecal transplantation] AND difficile) to 9 June 2016 yielded 415 articles.<br><br>CONTENT: Recent work has pointed to potential mechanisms by which microbiota restoration in the form of faecal transplantation has been efficacious. This includes studies of microorganisms associated with successful faecal transplantation in human and animal studies and a focus on bacterial bile acid metabolism as a mechanism that mediates colonization resistance against the pathogen. The potential use of microbiota manipulation for other diseases such as inflammatory bowel diseases and metabolic disorders will be discussed. The case will be made that the lessons learned from treatment of recurrent C.&#xa0;difficile infection may not necessarily translate to use of faecal transplantation or other methods to alter the microbiome for the treatment of other diseases.<br><br>IMPLICATIONS: A key conclusion that can be drawn is that understanding of the precise role of the microbiota in the pathogenesis of a specific disease is necessary prior to determining if microbiota manipulation represents a novel treatment therapy.}, }
@article {pmid27766987, year = {2017}, author = {Hecker, MT and Ho, E and Donskey, CJ}, title = {Fear of Failure: Engaging Patients in Antimicrobial Stewardship after Fecal Transplantation for Recurrent Clostridium difficile Infection.}, journal = {Infection control and hospital epidemiology}, volume = {38}, number = {1}, pages = {127-129}, doi = {10.1017/ice.2016.236}, pmid = {27766987}, issn = {1559-6834}, mesh = {*Antimicrobial Stewardship ; Clostridioides difficile ; Clostridium Infections/*therapy ; Enterocolitis, Pseudomembranous ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Inappropriate Prescribing/*statistics &amp; numerical data ; Patient Participation ; Recurrence ; Treatment Outcome ; }, }
@article {pmid27760583, year = {2017}, author = {Kuntz, JL and Baker, JM and Kipnis, P and Li, SX and Liu, V and Xie, Y and Marcella, S and Escobar, GJ}, title = {Utilization of Health Services Among Adults With Recurrent Clostridium difficile Infection: A 12-Year Population-Based Study.}, journal = {Infection control and hospital epidemiology}, volume = {38}, number = {1}, pages = {45-52}, pmid = {27760583}, issn = {1559-6834}, support = {K23 GM112018/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Algorithms ; Anti-Bacterial Agents/therapeutic use ; California/epidemiology ; Case-Control Studies ; Clostridioides difficile ; Clostridium Infections/*mortality/*therapy ; Fecal Microbiota Transplantation ; Female ; Health Services/*statistics &amp; numerical data ; Humans ; Male ; Middle Aged ; Recurrence ; Risk Factors ; }, abstract = {BACKGROUND Considerable efforts have been dedicated to developing strategies to prevent and treat recurrent Clostridium difficile infection (rCDI); however, evidence of the impact of rCDI on patient healthcare utilization and outcomes is limited. OBJECTIVE To compare healthcare utilization and 1-year mortality among adults who had rCDI, nonrecurrent CDI, or no CDI. METHODS We performed a nested case-control study among adult Kaiser Foundation Health Plan members from September 1, 2001, through December 31, 2013. We identified CDI through the presence of a positive laboratory test result and divided patients into 3 groups: patients with rCDI, defined as CDI in the 14-57 days after initial CDI; patients with nonrecurrent CDI; and patients who never had CDI. We conducted 3 matched comparisons: (1) rCDI vs no CDI; (2) rCDI vs nonrecurrent CDI; (3) nonrecurrent CDI vs no CDI. We followed patients for 1 year and compared healthcare utilization between groups, after matching patients on age, sex, and comorbidity. RESULTS We found that patients with rCDI consistently have substantially higher levels of healthcare utilization in various settings and greater 1-year mortality risk than both patients who had nonrecurrent CDI and patients who never had CDI. CONCLUSIONS Patients who develop an initial CDI are generally characterized by excess underlying, severe illness and utilization. However, patients with rCDI experience even greater adverse consequences of their disease than patients who do not experience rCDI. Our results further support the need for continued emphasis on identifying and using novel approaches to prevent and treat rCDI. Infect Control Hosp Epidemiol. 2016;1-8.}, }
@article {pmid27757227, year = {2016}, author = {Vieira, AT and Fukumori, C and Ferreira, CM}, title = {New insights into therapeutic strategies for gut microbiota modulation in inflammatory diseases.}, journal = {Clinical &amp; translational immunology}, volume = {5}, number = {6}, pages = {e87}, pmid = {27757227}, issn = {2050-0068}, abstract = {The interaction between the gut microbiota and the host immune system is very important for balancing and resolving inflammation. The human microbiota begins to form during childbirth; the complex interaction between bacteria and host cells becomes critical for the formation of a healthy or a disease-promoting microbiota. C-section delivery, formula feeding, a high-sugar diet, a high-fat diet and excess hygiene negatively affect the health of the microbiota. Considering that the majority of the global population has experienced at least one of these factors that can lead to inflammatory disease, it is important to understand strategies to modulate the gut microbiota. In this review, we will discuss new insights into gut microbiota modulation as potential strategies to prevent and treat inflammatory diseases. Owing to the great advances in tools for microbial analysis, therapeutic strategies such as prebiotic, probiotic and postbiotic treatment and fecal microbiota transplantation have gained popularity.}, }
@article {pmid27755271, year = {2016}, author = {Gianotti, RJ and Moss, AC}, title = {The Use and Efficacy of Fecal Microbiota Transplantation for Refractory Clostridium difficile in Patients with Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {22}, number = {11}, pages = {2704-2710}, doi = {10.1097/MIB.0000000000000950}, pmid = {27755271}, issn = {1536-4844}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridium difficile (CD) is an anaerobic, spore-forming bacillus that is responsible for a spectrum of gastrointestinal illness ranging from asymptomatic carriage to toxic megacolon and death. The prevalence of CD infection is increasing in both hospitalized and community-based inflammatory bowel disease populations. Standard antibiotic therapy fails to cure or prevent recurrence in more than 50% of patients, thus increasing the need for alternative therapies. Recently, fecal microbiota transplantation has received renewed attention as a therapy for refractory or recurrent CD infection. A high success rate combined with a favorable safety profile makes this therapy an attractive option for patients who have failed standard antibiotic therapy. Increasingly, this therapy is used in patients with CD infection and inflammatory bowel disease, as the combination of active inflammation and toxin-producing CD provides a challenging mix for clinicians.}, }
@article {pmid27751177, year = {2016}, author = {Wei, Y and Yang, J and Wang, J and Yang, Y and Huang, J and Gong, H and Cui, H and Chen, D}, title = {Successful treatment with fecal microbiota transplantation in patients with multiple organ dysfunction syndrome and diarrhea following severe sepsis.}, journal = {Critical care (London, England)}, volume = {20}, number = {1}, pages = {332}, pmid = {27751177}, issn = {1466-609X}, mesh = {Aged ; Aged, 80 and over ; Diarrhea/etiology/therapy ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/*methods/standards ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Multiple Organ Failure/etiology/*therapy ; RNA, Ribosomal, 16S/pharmacology/therapeutic use ; Sepsis/*complications ; Treatment Outcome ; }, abstract = {BACKGROUND: The dysbiosis of intestinal microbiota plays an important role in the development of gut-derived infections, making it a potential therapeutic target against multiple organ dysfunction syndrome (MODS) after sepsis. However, the effectiveness of fecal microbiota transplantation (FMT) in treating this disease has been rarely investigated.<br><br>METHODS: Two male patients, a 65-year-old and an 84-year-old, were initially diagnosed with cerebellar hemorrhage and cerebral infarction, respectively, after admission. During the course of hospitalization, both patients developed MODS, septic shock, and severe watery diarrhea. Demographic and clinical data were collected. Intestinal dysbiosis was confirmed by 16S rDNA-based molecular analysis of microbiota composition in fecal samples from the two patients. The two patients each received a single nasogastric infusion of sterile-filtered, pathogen-free feces from a healthy donor. Fecal samples were collected every two days post infusion to monitor changes in microbiota composition in response to treatment.<br><br>RESULTS: Following FMT, MODS and severe diarrhea were alleviated in both patients. Their stool output and body temperature markedly declined and normalized. Significant modification of microbiota composition, characterized by a profound increase of commensals in the Firmicutes phylum and depletion of opportunistic organisms in the Proteobacteria phylum, was observed in both patients. Furthermore, we identified a reconstituted bacterial community enriched in Firmicutes and depleted of Proteobacteria that was associated with a decrease in the patients' fecal output and in the levels of plasma inflammation markers.<br><br>CONCLUSIONS: The outcome of treating two patients with FMT indicates that restoration of the intestinal microbiota barrier can alleviate the infection and modulate the immune response. These findings warrant further investigation of FMT as a putative new therapy for treating microbiota-related diseases such as MODS.}, }
@article {pmid27718119, year = {2016}, author = {Seth, AK and Rawal, P and Bagga, R and Jain, P}, title = {Successful colonoscopic fecal microbiota transplantation for active ulcerative colitis: First report from India.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {35}, number = {5}, pages = {393-395}, pmid = {27718119}, issn = {0975-0711}, mesh = {Adrenal Cortex Hormones ; Adult ; Azathioprine ; Colitis, Ulcerative/*therapy ; *Colonoscopy ; Fecal Microbiota Transplantation/*methods ; Humans ; India ; Male ; Mesalamine ; Remission Induction ; Treatment Failure ; Treatment Outcome ; }, abstract = {Forty-four-year-old male with ulcerative colitis (UC) for 11 years reported frequent relapse despite daily sulfasalazine 4 g, azathioprine 125 mg, and rectal 5-aminosalicylic acid. Repeated use of corticosteroids led to cataract. At enrollment, he was passing eight stools a day with blood with a Mayo score of 9 (3+1+3+2). Stool was negative for ova/cysts/acid fast bacilli and Clostridium difficile toxin assay. Rectal biopsy showed cryptitis, crypt abscess, and crypt distortion with no inclusion bodies, and cytomegalovirus DNA was negative. Following informed consent and approval from IEC, three sessions of fecal microbiota transplant (FMT) were performed at intervals of 2 weeks. The donor was a 34-year-old relative with no history of gastrointestinal illness, no use of antibiotics over 3 months, and free from transmissible disease as per standard protocol. At colonoscopy, 350 mL of blended and filtered donor stool, drawn into seven syringes of 50 cm[3], was instilled from terminal ileum to sigmoid. Follow up sigmoidoscopy and rectal biopsy were done monthly for 6 months. There was symptomatic, colonoscopic, and histopathological improvement with the Mayo scores of 4.1 and 0 at 4.8 and 12 weeks post FMT. Azathioprine and sulfasalazine were tapered sequentially between months 4 and 6 of FMT. He remains in clinical and endoscopic remission 8 months after FMT and 2 months after withdrawal of all medication. Colonoscopic FMT may be effective in inducing drug-free remission in patients with active UC.}, }
@article {pmid27664398, year = {2017}, author = {Deng, YF and Liu, YY and Zhang, YT and Wang, Y and Liang, JB and Tufarelli, V and Laudadio, V and Liao, XD}, title = {Efficacy and role of inulin in mitigation of enteric sulfur-containing odor in pigs.}, journal = {Journal of the science of food and agriculture}, volume = {97}, number = {8}, pages = {2382-2391}, doi = {10.1002/jsfa.8050}, pmid = {27664398}, issn = {1097-0010}, mesh = {Animal Feed/analysis ; Animals ; Carbon-Sulfur Lyases/genetics/metabolism ; Fatty Acids, Volatile/metabolism ; Feces/chemistry/microbiology ; Intestine, Large/drug effects/microbiology ; Inulin/administration &amp; dosage/*pharmacology ; Male ; Metabolome/*drug effects ; Odorants/*analysis ; RNA, Ribosomal, 16S ; Sulfates/metabolism ; Sulfhydryl Compounds/metabolism ; Sulfur-Reducing Bacteria/classification/genetics/*growth &amp; development ; Sus scrofa/*growth &amp; development/metabolism/microbiology ; }, abstract = {BACKGROUND: The efficacy and role of inulin in the mitigation of enteric sulfur-containing odor gases hydrogen sulfide (H2 S) and methyl mercaptan (CH3 SH) in pigs were examined in this study. Twelve Duroc × Landrace × Yorkshire male finisher pigs (60.7 ± 1.9 kg), housed individually in open-circuit respiration chambers, were randomly assigned to two dietary groups, namely basal diet (control) and basal diet supplemented with 1% (w/w) inulin. At the end of the 45 day experiment, pigs were slaughtered and volatile fatty acid (VFA) concentration, sulfate radical (SO4[2][-]) concentration, population of sulfate-reducing bacteria (SRB) and expression of methionine gamma-lyase (MGL) gene were determined in contents from the caecum, colon (two segments) and rectum. Metabonomic analysis was used to compare differences in biochemical composition, and the Illumina MiSeq procedure to investigate differences in bacterial components, in the different parts of the large intestine between inulin-supplemented and inulin-free (control) groups.<br><br>RESULTS: Inulin decreased (P < 0.05) the average daily enteric H2 S and CH3 SH production by 12.4 and 12.1% respectively. The concentrations of acetate, propionate and butyrate in the large intestinal content were significantly increased (P < 0.05) with inulin treatment, whereas valerate concentration and MGL mRNA expression decreased (P < 0.05). The growth of Lactobacillus, Butyrivibrio, Pseudobutyrivibrio, Bifidobacterium and Clostridium butyricum was stimulated, while that of Desulfovibrio, the dominant SRB, was inhibited, and there was an accumulation of SO4[2-] in the large intestinal content of the inulin-supplemented pigs, suggesting that inulin mitigates H2 S generation from the SO4[2-] reduction pathway by reducing the growth of SRB.<br><br>CONCLUSION: The results showed that inulin mitigates CH3 SH generation via three methionine degradation metabolic pathways and H2 S generation from two cysteine degradation metabolic pathways, thus resulting in increased synthesis of these two sulfur-containing amino acids in the pig large intestine. &#xa9; 2016 Society of Chemical Industry.}, }
@article {pmid27592384, year = {2016}, author = {Li, D and Wang, P and Wang, P and Hu, X and Chen, F}, title = {The gut microbiota: A treasure for human health.}, journal = {Biotechnology advances}, volume = {34}, number = {7}, pages = {1210-1224}, doi = {10.1016/j.biotechadv.2016.08.003}, pmid = {27592384}, issn = {1873-1899}, mesh = {Aging/*immunology ; Evidence-Based Medicine ; Gastrointestinal Microbiome/*immunology ; Humans ; Immune System Diseases/immunology/*microbiology ; Metabolic Diseases/immunology/*microbiology ; Nervous System Diseases/*microbiology ; }, abstract = {The interplay between the host and host-associated gut microbiota is an area of increasing interest during the recent decade. From young infants to elderly people, from primitive tribes to modern societies, accumulating evidence has suggested the association of critical physiological roles of gut microbiota in the pathogenesis of a variety of human metabolic, immunological and neurological diseases. Importantly, it appears that the relationship between the gut microbiota and disease is bidirectional, instead of causal or consequential. Personalized nutritional and therapeutic strategies targeting the gut microbiota such as prebiotics, probiotics, drugs and fecal microbiota transplantation may create a new era in the human health.}, }
@article {pmid27517135, year = {2016}, author = {Ahmad, S and Bromberg, JS}, title = {Current status of the microbiome in renal transplantation.}, journal = {Current opinion in nephrology and hypertension}, volume = {25}, number = {6}, pages = {570-576}, pmid = {27517135}, issn = {1473-6543}, support = {R01 AI062765/AI/NIAID NIH HHS/United States ; R01 AI072039/AI/NIAID NIH HHS/United States ; R37 AI062765/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Diet ; Dysbiosis/*immunology/therapy ; Fecal Microbiota Transplantation ; Humans ; *Kidney Transplantation ; Microbiota/*immunology ; Probiotics ; Renal Insufficiency, Chronic/*microbiology ; T-Lymphocytes, Regulatory ; }, abstract = {PURPOSE OF REVIEW: An imbalance between pathogenic and protective microbiota characterizes dysbiosis. Presence of dysbiosis may affect immunity, tolerance, or disease depending on a variety of conditions. In the transplant patient population, the need for immunosuppression and widespread use of prophylactic and therapeutic antimicrobial agents create new posttransplant microbiota communities that remain to be fully defined.<br><br>RECENT FINDINGS: Studies in mice have demonstrated significant bidirectional interactions between microbiota-derived products and host immune cells. The stimulation of regulatory T cell and T helper cell type 17 cells by specific products leads to maintenance of immune homeostasis versus activation of inflammation, respectively. Dysbiosis may lead to development of antigen cross-reactivity, which may affect alloreactivity. Certain immunologic sequelae of microbiota are pronounced in chronic kidney disease, because of uremia and renal metabolism of microbiota metabolites. Dietary modifications, probiotics, and fecal microbiota transplant have been investigated for alteration of microbiota in humans.<br><br>SUMMARY: Researchers have begun to identify dysbioses associated with clinical conditions, including chronic kidney disease, posttransplant infection, and rejection. This information will allow clinicians not only to select at-risk patients for early intervention, but also to develop therapies that restore the microbiota to a state of homeostasis or tolerance.}, }
@article {pmid27743467, year = {2016}, author = {Qiao, YQ and Cai, CW and Ran, ZH}, title = {Therapeutic modulation of gut microbiota in inflammatory bowel disease: More questions to be answered.}, journal = {Journal of digestive diseases}, volume = {17}, number = {12}, pages = {800-810}, doi = {10.1111/1751-2980.12422}, pmid = {27743467}, issn = {1751-2980}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; *Diet ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Humans ; Inflammatory Bowel Diseases/complications/*microbiology/*therapy ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {Patients with inflammatory bowel disease (IBD) exhibit impaired control of the microbiome in the gut, and 'dysbiosis' is commonly observed. Western diet is a risk factor for the development of IBD, but it may have different effects on gut microbiota between IBD and non-IBD individuals. Exclusive enteral nutrition (EEN) can induce remission in pediatric Crohn's disease with a decrease in gut microbial diversity. Although there are some theoretical benefits, actual treatment effects of prebiotics and probiotics in IBD vary. High-quality studies have shown that VSL#3 (a high-potency probiotic medical food containing eight different strains) exhibits benefits in treating ulcerative colitis, and gut microbial diversity is reduced after treated with VSL#3 in animal models. The effect of fecal microbiome transplantation on IBD is controversial. Increasing microbial diversity compared with impaired handling of bacteria presents a dilemma. Antibiotics are the strongest factors in the reduction of microbiome ecological diversity. Some antibiotics may help to induce remission of the disease. Microbiome alteration has been suggested to be an intrinsic property of IBD and a potential predictor in diagnosis and prognosis. However, the effects of therapeutic modulations are variable; thus, more questions remain to be answered.}, }
@article {pmid27741152, year = {2016}, author = {Gasbarrini, G and Bonvicini, F and Gramenzi, A}, title = {Probiotics History.}, journal = {Journal of clinical gastroenterology}, volume = {50 Suppl 2, Proceedings from the 8th Probiotics, Prebiotics &amp; New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13-15, 2015}, number = {}, pages = {S116-S119}, doi = {10.1097/MCG.0000000000000697}, pmid = {27741152}, issn = {1539-2031}, mesh = {Fecal Microbiota Transplantation/*history ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; History, 20th Century ; History, Ancient ; Humans ; Probiotics/*history ; }, abstract = {Gut microbiota promotes healthy effects on the host and prevents diseases. Probiotic (probios, for life) are defined as "live microorganisms which when administered in adequate amounts confer a health benefit on the host." At the beginning of 1900s Louis Pasteur identified the microorganisms responsible for the process of fermentation, whereas E. Metchnikoff associated the enhanced longevity of Bulgarian rural people to the regular consumption of fermented dairy products such as yogurt. He suggested that lactobacilli might counteract the putrefactive effects of gastrointestinal metabolism that contributed to illness and aging. Hippocrates declared, 2000 years earlier, that "death sits in the bowels." Metchnikoff considered the lactobacilli as probiotics ("probios," conducive to life of the host as opposed to antibiotics); probiotics could have a positive influence on health and prevent aging. During the neolitic period of the age of the stone, the domestication of animals occurred and man began to get fermented food. Probably serendipitous contaminations in favorable environments played a major role. Fecal microbiota transplantation dates to a fourth-century Chinese handbook for food poisoning or severe diarrhea. To date fecal transplant cures Clostridium difficile infections with more efficacy than vancomycin, and prevents recurrence.}, }
@article {pmid27738605, year = {2016}, author = {Kumagai, H and Yokoyama, K and Imagawa, T and Inoue, S and Tulyeu, J and Tanaka, M and Yamagata, T}, title = {Failure of Fecal Microbiota Transplantation in a Three-Year-Old Child with Severe Refractory Ulcerative Colitis.}, journal = {Pediatric gastroenterology, hepatology &amp; nutrition}, volume = {19}, number = {3}, pages = {214-220}, pmid = {27738605}, issn = {2234-8646}, abstract = {Fecal microbiota transplantation (FMT) is a treatment designed to correct gut dysbiosis by administration of feces from a healthy volunteer. It is still unclear whether FMT for children with ulcerative colitis (UC) is effective or hazardous. Here we describe a young patient to have received FMT for UC. A three-year-old girl was admitted to our hospital with severe active UC, and treated with aminosalicylates and various immunosuppressive drugs. As remission was not achieved, we decided to try FMT before colectomy. We administered donor fecal material a total of six times by retention enema (×2) and via a nasoduodenal tube (×4) within 10 days. The patient developed abdominal pain and pyrexia after each FMT session. Analyses revealed the transferred donor fecal microbiota had not been retained by the patient, who ultimately underwent colectomy. The severity of the UC and/or timing of FMT may have partly accounted for the poor outcome.}, }
@article {pmid27730312, year = {2017}, author = {Nishida, A and Imaeda, H and Ohno, M and Inatomi, O and Bamba, S and Sugimoto, M and Andoh, A}, title = {Efficacy and safety of single fecal microbiota transplantation for Japanese patients with mild to moderately active ulcerative colitis.}, journal = {Journal of gastroenterology}, volume = {52}, number = {4}, pages = {476-482}, pmid = {27730312}, issn = {1435-5922}, mesh = {Adult ; Colitis, Ulcerative/microbiology/*therapy ; Colonoscopy/methods ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Japan ; Male ; Middle Aged ; Remission Induction ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: The clinical utility of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC) is still controversial. We investigated the efficacy and safety of single FMT for patients with mild to moderately active UC in a Japanese population.<br><br>METHODS: Fifty-seven patients were evaluated for eligibility, and 16 patients were excluded. Forty-one patients with UC refractory to standard medical therapy were treated with single FMT by colonoscopic administration. Changes in the fecal microbiota were assessed by 16S ribosomal DNA based terminal restriction fragment length polymorphism analysis.<br><br>RESULTS: At 8&#xa0;weeks after FMT, no patient achieved clinical remission, and 11 of 41 patients (26.8&#xa0;%) showed clinical response. The full Mayo score and the Mayo clinical score significantly decreased at week 8 [full Mayo score 5.5&#xa0;&#xb1;&#xa0;2.4 (mean&#xa0;&#xb1;&#xa0;standard deviation) at initiation and 4.6&#xa0;&#xb1;&#xa0;2.2 at week 8, P&#xa0;<&#xa0;0.004; Mayo clinical score 4.0&#xa0;&#xb1;&#xa0;2.0 at initiation and 3.0&#xa0;&#xb1;&#xa0;1.9 at week 8, P&#xa0;<&#xa0;0.001], but there were no statistically significant effects on the Mayo endoscopic score. No adverse events occurred after FMT or during the follow-up period of 8&#xa0;weeks. The proportion of Bifidobacterium was significantly higher in the donor feces used for responders than in the donor feces used for nonresponders. The proportion of Lactobacillales and Clostridium cluster IV were significantly higher in the donor feces used for nonresponders.<br><br>CONCLUSIONS: Single FMT by colonoscopy was performed safely in all patients, but sufficient clinical efficacy and microbial restoration were not confirmed in patients with mild to moderately active UC.}, }
@article {pmid27729007, year = {2016}, author = {Diao, H and Yan, HL and Xiao, Y and Yu, B and Yu, J and He, J and Zheng, P and Zeng, BH and Wei, H and Mao, XB and Chen, DW}, title = {Intestinal microbiota could transfer host Gut characteristics from pigs to mice.}, journal = {BMC microbiology}, volume = {16}, number = {1}, pages = {238}, pmid = {27729007}, issn = {1471-2180}, mesh = {Animals ; Animals, Newborn ; CDX2 Transcription Factor/genetics ; Fecal Microbiota Transplantation/methods/*veterinary ; Feces/microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; High-Throughput Nucleotide Sequencing/methods ; Intestinal Mucosa/metabolism/microbiology ; Intestine, Small/metabolism/microbiology ; Intestines/growth &amp; development/*microbiology ; Mice ; Mice, Inbred BALB C ; Phenotype ; RNA, Messenger/biosynthesis ; Swine/*microbiology ; }, abstract = {BACKGROUND: The present study was conducted to compare the differences in gut microbiota composition and gut-phenotypes among pig breeds, and determine whether these differences would transmit to mice colonized with fecal microbiota of different pig breeds. A total of 24 1-day-old germ-free BALB/C mice were divided into 3 groups (TFM, YFM and RFM), which were transplanted with intact fecal microbiota of Tibetan pig (TP), Yorkshire pig (YP) and Rongchang pig (RP), respectively.<br><br>RESULTS: Results showed that different pig breeds exhibited distinct gut microbiota profile based on high-throughput pyrosequencing. YP exhibited a lower Firmicutes/Bacteroidetes ratio and apparent genera differences compared with RP and TP, and higher levels of bacteria from Spirochaetes were observed in TP compared with RP and YP (P&#x2009;<&#x2009;0.05). Transplanted porcine microbiota into GF mice replicated the phenotypes of pig donors. Moreover, the three groups of donor pigs and their mice recipients exhibited different intestinal index and morphology. TP and RP had higher intestinal weight and relative CDX2 mRNA expression in ileum than YP, and longer intestine, higher villus height of duodenum and jejunum were observed in TP compared with YP and RP (P&#x2009;<&#x2009;0.05). TP exhibited higher GLP-2 mRNA expression in duodenum and jejunum than RP (P&#x2009;<&#x2009;0.05). Similarly, YFM had lower intestine weight and CDX2 mRNA expression in ileum than TFM and RFM (P&#x2009;<&#x2009;0.05). The intestine length in TFM was longer than that in RFM, and TFM had higher villus height in duodenum and jejunum and GLP-2 mRNA expression in ileum than the other two groups (P&#x2009;<&#x2009;0.05). Besides, the digestive and absorptive ability was different among the three groups in donor pigs and mice recipients. YP had higher jejunal lactase and maltase activities than TP and RP, while TP had higher activities of jejunal ATPase, &#x3b3;-GT, and relative SGLT1 mRNA expression in duodenum and jejunum than YP and RP (P&#x2009;<&#x2009;0.05). Likewise, YFM had higher jejunal sucrase and maltase activities than TFM and RFM, whereas higher jejunal &#x3b3;-GT activity and relative SGLT1 mRNA expression in duodenum and ileum were observed in TFM compared with YFM and RFM (P&#x2009;<&#x2009;0.05). In addition, Tibetan pigs-derived microbiota improved gut barrier in mice recipients. The concentration of MDA in YP was higher than that in TP and RP (P&#x2009;=&#x2009;0.078), and the relative ZO-1 mRNA expression in ileum in TP was higher than that in YP (P&#x2009;<&#x2009;0.05). Likely, compared with TFM and RFM, YFM exhibited increasing MDA concentration in jejunum (P&#x2009;=&#x2009;0.098), and the relative ZO-1 mRNA expression in duodenum and ileum in TFM were higher than that in YFM (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: There were huge differences in gut microbiota composition and gut characteristics among pig breeds, and gut microbiota could partially convey host gut characteristics from pigs to mice.}, }
@article {pmid27724956, year = {2016}, author = {Jalanka, J and Mattila, E and Jouhten, H and Hartman, J and de Vos, WM and Arkkila, P and Satokari, R}, title = {Long-term effects on luminal and mucosal microbiota and commonly acquired taxa in faecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {BMC medicine}, volume = {14}, number = {1}, pages = {155}, pmid = {27724956}, issn = {1741-7015}, mesh = {*Clostridioides difficile ; Clostridium Infections/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). It restores the disrupted intestinal microbiota and subsequently suppresses C. difficile. The long-term stability of the intestinal microbiota and the recovery of mucosal microbiota, both of which have not been previously studied, are assessed herein. Further, the specific bacteria behind the treatment efficacy are also investigated.<br><br>METHODS: We performed a high-throughput microbiota profiling using a phylogenetic microarray analysis of 131 faecal and mucosal samples from 14 rCDI patients pre- and post-FMT during a 1-year follow-up and 23 samples from the three universal donors over the same period.<br><br>RESULTS: The FMT treatment was successful in all patients. FMT reverted the patients' bacterial community to become dominated by Clostridium clusters IV and XIVa, the major anaerobic bacterial groups of the healthy gut. In the mucosa, the amount of facultative anaerobes decreased, whereas Bacteroidetes increased. Post-FMT, the patients' microbiota profiles were more similar to their own donors than what is generally observed for unrelated subjects and this striking similarity was retained throughout the 1-year follow-up. Furthermore, the universal donor approach allowed us to identify bacteria commonly established in all CDI patients and revealed a commonly acquired core microbiota consisting of 24 bacterial taxa.<br><br>CONCLUSIONS: FMT induces profound microbiota changes, therefore explaining the high clinical efficacy for rCDI. The identification of commonly acquired bacteria could lead to effective bacteriotherapeutic formulations. FMT can affect microbiota in the long-term and offers a means to modify it relatively permanently for the treatment of microbiota-associated diseases.}, }
@article {pmid27722099, year = {2016}, author = {Singh, S}, title = {Congenital toxoplasmosis: Clinical features, outcomes, treatment, and prevention.}, journal = {Tropical parasitology}, volume = {6}, number = {2}, pages = {113-122}, pmid = {27722099}, issn = {2229-5070}, abstract = {Toxoplasmosis is caused by a coccidian parasite, Toxoplasma gondii. The parasite is highly prevalent both in humans and in warm-blooded animals. Cat family animals are definitive host, and these animals excrete the infective oocysts in their feces. Humans, though not definitive host, get infection by consuming water or food contaminated with cat feces. Rarely, infection can also take place through transfusing the infected blood, through transplantation of infected organs, or transplacentally from infected mother to fetus. Transplacental infection can cause congenital infection with varied degree of clinical manifestations, which depend on the age of fetus when infection took place. Diagnosis of congenital toxoplasmosis is difficult to establish until it is suspected and laboratory investigations are carried out. In more than 75% of cases, acute infection is missed due to very mild or unnoticeable clinical symptoms and signs. In India, a prevalence rate of 22.4% (8.8-37.3%) has been reported with an overall IgM positivity of 1.43%. It is estimated that approximately between 56,737 and 176,882 children per year are born in India with a possible risk of congenital toxoplasmosis. The diagnosis of congenital toxoplasmosis can be made by serological methods which are most commonly used. The other methods are parasite isolation by culture and molecular methods. Toxoplasmosis is treatable and transplacental transmission can be prevented by spiramycin, which concentrates in the placenta. However, if infection has done any damage to the fetus or the parasite has passed the placenta, spiramycin cannot reverse the damage. Prevention remains the best remedy.}, }
@article {pmid27720396, year = {2016}, author = {Carlucci, C and Petrof, EO and Allen-Vercoe, E}, title = {Fecal Microbiota-based Therapeutics for Recurrent Clostridium difficile Infection, Ulcerative Colitis and Obesity.}, journal = {EBioMedicine}, volume = {13}, number = {}, pages = {37-45}, pmid = {27720396}, issn = {2352-3964}, support = {R21 AI121575/AI/NIAID NIH HHS/United States ; R33 AI121575/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Colitis, Ulcerative/microbiology/*therapy ; Dysbiosis ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Obesity/microbiology/*therapy ; Recurrence ; Treatment Outcome ; }, abstract = {The human gut microbiome is a complex ecosystem of fundamental importance to human health. Our increased understanding of gut microbial composition and functional interactions in health and disease states has spurred research efforts examining the gut microbiome as a valuable target for therapeutic intervention. This review provides updated insight into the state of the gut microbiome in recurrent Clostridium difficile infection (CDI), ulcerative colitis (UC), and obesity while addressing the rationale for the modulation of the gut microbiome using fecal microbiota transplant (FMT)-based therapies. Current microbiome-based therapeutics in pre-clinical or clinical development are discussed. We end by putting this within the context of the current regulatory framework surrounding FMT and related therapies.}, }
@article {pmid27718300, year = {2017}, author = {Do, T}, title = {Insights into microbial ecosystems using a new computational approach.}, journal = {Oral diseases}, volume = {23}, number = {7}, pages = {817-819}, doi = {10.1111/odi.12591}, pmid = {27718300}, issn = {1601-0825}, mesh = {Clostridioides difficile ; Computational Biology ; Dysbiosis/*complications ; Enterocolitis, Pseudomembranous/therapy ; Fecal Microbiota Transplantation ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; }, }
@article {pmid27703036, year = {2016}, author = {Fenollar, F and Raoult, D}, title = {Does Bacterial Vaginosis Result From Fecal Transplantation?.}, journal = {The Journal of infectious diseases}, volume = {214}, number = {11}, pages = {1784}, doi = {10.1093/infdis/jiw472}, pmid = {27703036}, issn = {1537-6613}, mesh = {Dysbiosis/etiology/microbiology ; *Fecal Microbiota Transplantation/adverse effects/statistics &amp; numerical data ; Female ; Humans ; Vagina/microbiology ; *Vaginosis, Bacterial/etiology/microbiology ; }, }
@article {pmid27698622, year = {2016}, author = {Marotz, CA and Zarrinpar, A}, title = {Treating Obesity and Metabolic Syndrome with Fecal Microbiota Transplantation.}, journal = {The Yale journal of biology and medicine}, volume = {89}, number = {3}, pages = {383-388}, pmid = {27698622}, issn = {1551-4056}, support = {K08 DK102902/DK/NIDDK NIH HHS/United States ; T32 DK007202/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Metabolic Syndrome/*microbiology/*therapy ; Obesity/*microbiology/*therapy ; }, abstract = {The worldwide prevalence of metabolic syndrome, which includes obesity and its associated diseases, is rising rapidly. The human gut microbiome is recognized as an independent environmental modulator of host metabolic health and disease. Research in animal models has demonstrated that the gut microbiome has the functional capacity to induce or relieve metabolic syndrome. One way to modify the human gut microbiome is by transplanting fecal matter, which contains an abundance of live microorganisms, from a healthy individual to a diseased one in the hopes of alleviating illness. Here we review recent evidence suggesting efficacy of fecal microbiota transplant (FMT) in animal models and humans for the treatment of obesity and its associated metabolic disorders.}, }
@article {pmid27691983, year = {2016}, author = {Sohn, KM and Cheon, S and Kim, YS}, title = {Can Fecal Microbiota Transplantation (FMT) Eradicate Fecal Colonization With Vancomycin-Resistant Enterococci (VRE)?.}, journal = {Infection control and hospital epidemiology}, volume = {37}, number = {12}, pages = {1519-1521}, doi = {10.1017/ice.2016.229}, pmid = {27691983}, issn = {1559-6834}, mesh = {Aged ; Enterococcus faecium/*isolation &amp; purification ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Gram-Positive Bacterial Infections/diagnosis/*therapy ; Humans ; Treatment Outcome ; Vancomycin-Resistant Enterococci/*isolation &amp; purification ; }, }
@article {pmid27689204, year = {2016}, author = {van Beurden, YH and van Gils, T and van Gils, NA and Kassam, Z and Mulder, CJ and Aparicio-Pagés, N}, title = {Serendipity in Refractory Celiac Disease: Full Recovery of Duodenal Villi and Clinical Symptoms after Fecal Microbiota Transfer.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {25}, number = {3}, pages = {385-388}, doi = {10.15403/jgld.2014.1121.253.cel}, pmid = {27689204}, issn = {1842-1121}, mesh = {Aged ; Atrophy ; Celiac Disease/diagnosis/microbiology/*surgery ; Clostridioides difficile/*pathogenicity ; Duodenum/*microbiology/pathology ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*surgery ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Microvilli/microbiology/pathology ; Recurrence ; Treatment Outcome ; }, abstract = {Treatment of refractory celiac disease type II (RCD II) and preventing the development of an enteropathy associated T-cell lymphoma in these patients is still difficult. In this case report, we describe a patient with RCD II who received fecal microbiota transfer as treatment for a recurrent Clostridium difficile infection, and remarkably showed a full recovery of duodenal villi and disappearance of celiac symptoms. This case suggests that altering the gut microbiota may hold promise in improving the clinical and histological consequences of celiac disease and/or RCD II.}, }
@article {pmid27687850, year = {2016}, author = {Giorgio, F and Ierardi, E and Sorrentino, C and Principi, M and Barone, M and Losurdo, G and Iannone, A and Giangaspero, A and Monno, R and Di Leo, A}, title = {Helicobacter pylori DNA isolation in the stool: an essential pre-requisite for bacterial noninvasive molecular analysis.}, journal = {Scandinavian journal of gastroenterology}, volume = {51}, number = {12}, pages = {1429-1432}, doi = {10.1080/00365521.2016.1216592}, pmid = {27687850}, issn = {1502-7708}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Biopsy ; Clarithromycin/*therapeutic use ; DNA, Bacterial/*isolation &amp; purification ; Drug Resistance, Bacterial/*genetics ; Feces/microbiology ; Female ; Helicobacter Infections/*diagnosis/drug therapy ; *Helicobacter pylori ; Humans ; Italy ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Point Mutation ; Real-Time Polymerase Chain Reaction ; Young Adult ; }, abstract = {PURPOSE: Real-time polymerase chain reaction (RT-PCR) is a widely used technique for bacterial and viral infection diagnosis. Herein, we report our preliminary experience in retrieving H. pylori genetic sequences in stools and analyzing genotypic clarithromycin resistance by RT-PCR (noninvasive), with the aim of comparing this procedure with that performed on biopsy samples (invasive).<br><br>MATERIALS AND METHODS: After 'in vitro' demonstration of H. pylori DNA detection from pure and stool-mixed bacteria, 52 consecutive patients at the first diagnosis of infection were investigated. DNA was extracted from biopsy tissue and stool samples (THD[&#xae;] Fecal Test, Italy). RT-PCR was performed to detect 23S rRNA encoding bacterial subunit gene and search A2143G, A2142C, A2142G point mutations for clarithromycin resistance assessment.<br><br>RESULTS: RT-PCR showed H. pylori positive DNA in all infected patients with full concordance between tissue and stool detection (100%). We found A2143G mutation in 10 (19.2%), A2142G in 4 (7.7%) and A2142C in 5 (9.6%) patients; there was a full agreement between biopsy and fecal samples. A2143G was found in all the four A2142G positive cases and in three out of the five A2142C positive strains. Overall clarithromycin resistance rate in our series was 23%.<br><br>CONCLUSIONS: Despite the need of confirmation on large sample, stool RT-PCR analysis could represent a feasible tool to detect H. pylori DNA sequences and antibiotic resistance point mutations. As compared to tissue molecular analysis, this technique is noninvasive, with potential advantages such as improvement of patient compliance, reduction of diagnostic procedure time/cost and improvement of therapeutic outcome.}, }
@article {pmid27681266, year = {2017}, author = {Tourret, J and Willing, BP and Dion, S and MacPherson, J and Denamur, E and Finlay, BB}, title = {Immunosuppressive Treatment Alters Secretion of Ileal Antimicrobial Peptides and Gut Microbiota, and Favors Subsequent Colonization by Uropathogenic Escherichia coli.}, journal = {Transplantation}, volume = {101}, number = {1}, pages = {74-82}, doi = {10.1097/TP.0000000000001492}, pmid = {27681266}, issn = {1534-6080}, mesh = {Animals ; Antimicrobial Cationic Peptides/*metabolism ; Drug Therapy, Combination ; Escherichia coli Infections/immunology/microbiology ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Ileum/*drug effects/immunology/metabolism/microbiology ; Immunocompromised Host ; Immunosuppressive Agents/*toxicity ; Lectins, C-Type/genetics/immunology ; Mice, Inbred C57BL ; Models, Animal ; Mycophenolic Acid/*toxicity ; Opportunistic Infections/immunology/microbiology ; Prednisolone/*toxicity ; Reverse Transcriptase Polymerase Chain Reaction ; Ribotyping ; Tacrolimus/*toxicity ; Time Factors ; Urinary Tract Infections/immunology/microbiology ; Uropathogenic Escherichia coli/*growth &amp; development/immunology/pathogenicity ; }, abstract = {BACKGROUND: Transplant recipients are treated with immunosuppressive (IS) therapies, which impact host-microbial interactions. We examined the impact of IS drugs on gut microbiota and on the expression of ileal antimicrobial peptides.<br><br>METHODS: Mice were treated for 14 days with prednisolone, mycophenolate mofetil, tacrolimus, a combination of these 3 drugs, everolimus, or water. Feces were collected before and after treatment initiation. Ileal samples were collected after sacrifice. Fecal and ileal microbiota were analyzed by pyrosequencing of 16S rRNA genes and enumeration of selected bacteria by culture, and C-type lectins were assessed in ileal tissues by reverse transcriptase-quantitative polymerase chain reaction.<br><br>RESULTS: Prednisolone disrupted fecal microbiota community structure, decreased Bacteroidetes, and increased Firmicutes in the feces. Prednisolone, tacrolimus, and mycophenolate mofetil modified fecal microbiota at the family level in each experimental replicate, but changes were not consistent between the replicates. In ileal samples, the genus Clostridium sensu stricto was dramatically reduced in the prednisolone and combined IS drug groups. These modifications corresponded to an altered ileal expression of C-type lectins Reg3&#x3b3; and Reg3&#x3b2;, and of interleukin 22. Interestingly, the combined IS treatment enabled a commensal Escherichia coli to flourish, and dramatically increased colonization by uropathogenic E. coli strain 536.<br><br>CONCLUSIONS: IS treatment alters innate antimicrobial defenses and disrupts the gut microbiota, which leads to overgrowth of indigenous E. coli and facilitates colonization by opportunistic pathogens.}, }
@article {pmid27679719, year = {2016}, author = {Fwu, CW and Kimmel, PL and Eggers, PW and Abbott, KC}, title = {Comparison of trends in colorectal cancer screening in the US end-stage renal disease population and the US Medicare population.}, journal = {Clinical kidney journal}, volume = {9}, number = {5}, pages = {722-728}, pmid = {27679719}, issn = {2048-8505}, abstract = {BACKGROUND: Although patients treated with maintenance hemodialysis are at an increased risk of colorectal cancer compared with the general population, national practices for colorectal cancer screening have not been reported in this population. We assessed the performance of colorectal cancer screening in the US end-stage renal disease program in comparison with the US Medicare population.<br><br>METHODS: We studied the United States Renal Data System for US prevalent hemodialysis patients between 2002 and 2011 who had Medicare as their primary insurer. We assessed procedure codes for performance of common colorectal cancer screening tests, including fecal occult blood testing, sigmoidoscopy and colonoscopy. We assessed screening sigmoidoscopy and screening colonoscopy only and excluded patients who had preexisting colon cancer or gastrointestinal hemorrhage. Because colorectal cancer screening recommendations are established for hemodialysis patients who have been listed for kidney transplantation, but no general recommendations exist for patients who are not wait-listed, we assessed colorectal cancer screening separately for the two groups.<br><br>RESULTS: We found that 1-year performance of colonoscopy in wait-listed hemodialysis patients was similar to or higher than that in general Medicare patients of the same age, while performance of colonoscopy in non-wait-listed patients was significantly lower than among general Medicare patients of the same age.<br><br>CONCLUSIONS: Given improved survival among hemodialysis patients in the last decade, the utility of colorectal cancer screening even among non-wait-listed hemodialysis patients should be reassessed.}, }
@article {pmid27664230, year = {2016}, author = {Oppfeldt, AM and Dahlerup, JF and Christensen, LA and Hvas, CL}, title = {Faecal microbiota transplantation for recurring Clostridium difficile infection in a patient with Crohn's disease and ileorectal anastomosis.}, journal = {BMJ case reports}, volume = {2016}, number = {}, pages = {}, pmid = {27664230}, issn = {1757-790X}, abstract = {Faecal microbiota transplantation (FMT) is increasingly being used to treat refractory and recurring Clostridium difficile infection (CDI). Although FMT appears to be safe and highly effective in patients with a preserved colon and immunocompetence, its use in patients with inflammatory bowel disease (IBD) who are on immunomodulating therapies is controversial. In particular, patients who have undergone colectomy may have different treatment responses to FMT. In this case report, we describe the successful use of FMT in a female patient aged 19 years with Crohn's disease who underwent ileorectal anastomosis following colectomy. She had recurrent CDIs that were refractory to metronidazole, pulse-tapered vancomycin and fidaxomicin treatments. She underwent 2 FMTs, which were performed via sigmoidoscopy; her mother served as a donor. Follow-up was conducted for 12 months and indicated sustained remission of CDI.}, }
@article {pmid27658471, year = {2016}, author = {Hagel, S and Fischer, A and Ehlermann, P and Frank, T and Tueffers, K and Sturm, A and Link, A and Demir, M and Siebenhaar, A and Storr, M and Glueck, T and Siegel, E and Solbach, P and Goeser, F and Koelbel, CB and Lohse, A and Luebbert, C and Kandzi, U and Maier, M and Schuerle, S and Lerch, MM and Tacke, D and Cornely, OA and Stallmach, A and Vehreschild, M and , }, title = {Fecal Microbiota Transplant in Patients With Recurrent Clostridium Difficile Infection.}, journal = {Deutsches Arzteblatt international}, volume = {113}, number = {35-36}, pages = {583-589}, pmid = {27658471}, issn = {1866-0452}, mesh = {Aged ; Aged, 80 and over ; Clostridium Infections/microbiology/*mortality/*therapy ; Fecal Microbiota Transplantation/methods/*mortality/*statistics &amp; numerical data ; Female ; Germany/epidemiology ; Humans ; Male ; Middle Aged ; Prevalence ; Recurrence ; *Registries ; Risk Factors ; Survival Rate ; Treatment Outcome ; }, abstract = {BACKGROUND: The clinical effectiveness of fecal microbiota transplant (FMT) for the treatment of recurrent Clostridium difficile infections (rCDI) has been demonstrated in randomized controlled trials. To assess the current status of FMT in Germany with respect to active centers, local standards, clinical effectiveness and safety, the MicroTrans Registry (NCT02681068) was established.<br><br>METHODS: In a long-term retrospective multicenter observational study by the German Clinical Microbiome Study Group (GCMSG), primary and secondary cure on day 30 and 90, as well as occurrence of treatment-related adverse events were assessed. In addition to patient demographic data, we provide an overview of the FMT procedures and techniques used at different centers.<br><br>RESULTS: Overall, 133 eligible patients from 33 centers were included, of which 64.7% were female (n = 86). The mean age was 75 years (interquartile range: 59.5-81.5). Administration via the duodenal route (n = 59; 44.4%) was the most frequently applied option, followed by colonic (n = 55; 41.1%), capsule (n = 13; 9.8%), and gastric administration (n = 4; 3.0%). Primary cure on day 30 and 90 was achieved in 84.2% (n = 101/120) and 78.3% (n = 72/92) of patients, respectively. Including re-treatment, secondary response was achieved in 87.5% (d 30; n = 105/120) and 85.9% (d 90; n = 79/92), respectively. Treatment- elated adverse events were documented in 16 patients (12.0%).<br><br>CONCLUSION: FMT is a safe and effective treatment option for rCDI. However, FMT is currently available only in few centers in Germany, and treatment options vary from one center to another.}, }
@article {pmid27657145, year = {2016}, author = {Culligan, EP and Sleator, RD}, title = {Advances in the Microbiome: Applications to Clostridium difficile Infection.}, journal = {Journal of clinical medicine}, volume = {5}, number = {9}, pages = {}, pmid = {27657145}, issn = {2077-0383}, abstract = {Clostridium difficile is a major cause of morbidity and mortality worldwide, causing over 400,000 infections and approximately 29,000 deaths in the United States alone each year. C. difficile is the most common cause of nosocomial diarrhoea in the developed world, and, in recent years, the emergence of hyper-virulent (mainly ribotypes 027 and 078, sometimes characterised by increased toxin production), epidemic strains and an increase in the number of community-acquired infections has caused further concern. Antibiotic therapy with metronidazole, vancomycin or fidaxomicin is the primary treatment for C. difficile infection (CDI). However, CDI is unique, in that, antibiotic use is also a major risk factor for acquiring CDI or recurrent CDI due to disruption of the normal gut microbiota. Therefore, there is an urgent need for alternative, non-antibiotic therapeutics to treat or prevent CDI. Here, we review a number of such potential treatments which have emerged from advances in the field of microbiome research.}, }
@article {pmid27650128, year = {2016}, author = {Verwoerd, A and Ter Haar, NM and de Roock, S and Vastert, SJ and Bogaert, D}, title = {The human microbiome and juvenile idiopathic arthritis.}, journal = {Pediatric rheumatology online journal}, volume = {14}, number = {1}, pages = {55}, pmid = {27650128}, issn = {1546-0096}, mesh = {*Arthritis, Juvenile/immunology/microbiology ; *Autoimmunity ; Humans ; Microbiota/*immunology ; }, abstract = {Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. The pathogenesis of JIA is thought to be the result of a combination of host genetic and environmental triggers. However, the precise factors that determine one's susceptibility to JIA remain to be unravelled. The microbiome has received increasing attention as a potential contributing factor to the development of a wide array of immune-mediated diseases, including inflammatory bowel disease, type 1 diabetes and rheumatoid arthritis. Also in JIA, there is accumulating evidence that the composition of the microbiome is different from healthy individuals. A growing body of evidence indeed suggests that, among others, the microbiome may influence the development of the immune system, the integrity of the intestinal mucosal barrier, and the differentiation of T cell subsets. In turn, this might lead to dysregulation of the immune system, thereby possibly playing a role in the development of JIA. The potential to manipulate the microbiome, for example by faecal microbial transplantation, might then offer perspectives for future therapeutic interventions. Before we can think of such interventions, we need to first obtain a deeper understanding of the cause and effect relationship between JIA and the microbiome. In this review, we discuss the existing evidence for the involvement of the microbiome in JIA pathogenesis and explore the potential mechanisms through which the microbiome may influence the development of autoimmunity in general and JIA specifically.}, }
@article {pmid27648810, year = {2017}, author = {Meisel, M and Mayassi, T and Fehlner-Peach, H and Koval, JC and O'Brien, SL and Hinterleitner, R and Lesko, K and Kim, S and Bouziat, R and Chen, L and Weber, CR and Mazmanian, SK and Jabri, B and Antonopoulos, DA}, title = {Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis.}, journal = {The ISME journal}, volume = {11}, number = {1}, pages = {15-30}, pmid = {27648810}, issn = {1751-7370}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DK067180/DK/NIDDK NIH HHS/United States ; R01 DK078938/DK/NIDDK NIH HHS/United States ; T32 AI007090/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/*metabolism ; Butyrates/*metabolism ; Colitis/genetics/*metabolism/microbiology/therapy ; Disease Susceptibility ; Dysbiosis/genetics/metabolism/*microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Interleukin-15/genetics/*metabolism ; Intestinal Mucosa/metabolism/microbiology ; Intestines/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {Dysbiosis resulting in gut-microbiome alterations with reduced butyrate production are thought to disrupt intestinal immune homeostasis and promote complex immune disorders. However, whether and how dysbiosis develops before the onset of overt pathology remains poorly defined. Interleukin-15 (IL-15) is upregulated in distressed tissue and its overexpression is thought to predispose susceptible individuals to and have a role in the pathogenesis of celiac disease and inflammatory bowel disease (IBD). Although the immunological roles of IL-15 have been largely studied, its potential impact on the microbiota remains unexplored. Analysis of 16S ribosomal RNA-based inventories of bacterial communities in mice overexpressing IL-15 in the intestinal epithelium (villin-IL-15 transgenic (v-IL-15tg) mice) shows distinct changes in the composition of the intestinal bacteria. Although some alterations are specific to individual intestinal compartments, others are found across the ileum, cecum and feces. In particular, IL-15 overexpression restructures the composition of the microbiota with a decrease in butyrate-producing bacteria that is associated with a reduction in luminal butyrate levels across all intestinal compartments. Fecal microbiota transplant experiments of wild-type and v-IL-15tg microbiota into germ-free mice further indicate that diminishing butyrate concentration observed in the intestinal lumen of v-IL-15tg mice is the result of intrinsic alterations in the microbiota induced by IL-15. This reconfiguration of the microbiota is associated with increased susceptibility to dextran sodium sulfate-induced colitis. Altogether, this study reveals that IL-15 impacts butyrate-producing bacteria and lowers butyrate levels in the absence of overt pathology, which represent events that precede and promote intestinal inflammatory diseases.}, }
@article {pmid27648772, year = {2016}, author = {Chapman, BC and Moore, HB and Overbey, DM and Morton, AP and Harnke, B and Gerich, ME and Vogel, JD}, title = {Fecal microbiota transplant in patients with Clostridium difficile infection: A systematic review.}, journal = {The journal of trauma and acute care surgery}, volume = {81}, number = {4}, pages = {756-764}, doi = {10.1097/TA.0000000000001195}, pmid = {27648772}, issn = {2163-0763}, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) restores a diverse bacterial profile to the gastrointestinal tract and may effectively treat patients with Clostridium difficile infection (CDI). The objective of this systematic review was to evaluate the effectiveness of FMT in the treatment of CDI.<br><br>METHODS: Ovid MEDLINE, EMBASE, Web of Science, and Cochrane database were used. The authors searched studies with 10 or more patients examining the resolution of symptoms after FMT in patients with CDI. Reviews, letters to the editors, and abstracts were excluded. Participants were patients with CDI. Intervention used was FMT. Quality assessment was performed using the Cochrane risk of bias assessment tool. Results were synthesized using a narrative approach.<br><br>RESULTS: Retrospective and uncontrolled prospective cohort studies suggest that FMT is a highly effective therapy for recurrent/refractory CDI, with clinical success rates ranging from 83% to 100%, which is similar to rates published by two randomized controlled trials. Fecal microbiota transplantation may be effectively administered via antegrade (upper gastrointestinal) or retrograde (lower gastrointestinal) routes of delivery. Fecal microbiota transplantation rarely results in major adverse events. However, diarrhea, cramping, and bloating commonly occur and are typically self-limited. Most studies were uncontrolled retrospective studies.<br><br>CONCLUSION: Fecal microbiota transplantation should be considered in patients with recurrent episodes of mild to moderate CDI who have failed conventional antimicrobial therapy. There is insufficient evidence to recommend FMT for the treatment of severe CDI.<br><br>LEVEL OF EVIDENCE: Systematic review, level III.}, }
@article {pmid27646933, year = {2017}, author = {Rotman, Y and Sanyal, AJ}, title = {Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease.}, journal = {Gut}, volume = {66}, number = {1}, pages = {180-190}, doi = {10.1136/gutjnl-2016-312431}, pmid = {27646933}, issn = {1468-3288}, mesh = {Anti-Obesity Agents/therapeutic use ; Antioxidants/therapeutic use ; Chenodeoxycholic Acid/*analogs &amp; derivatives/therapeutic use ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; Drug Discovery ; Drug Repositioning ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Immunologic Factors/therapeutic use ; Incretins/therapeutic use ; Lipogenesis/drug effects ; Molecular Targeted Therapy ; Non-alcoholic Fatty Liver Disease/*drug therapy ; Peroxisome Proliferator-Activated Receptors/*agonists ; Receptors, Cytoplasmic and Nuclear/*agonists ; Tumor Necrosis Factor-alpha/antagonists &amp; inhibitors ; }, abstract = {Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking. Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy as well. A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents. NAFLD therapies target four main pathways. The dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress. Medications in this group include peroxisome proliferator-activator receptor agonists (eg, pioglitazone, elafibranor, saroglitazar), medications targeting the bile acid-farnesoid X receptor axis (obeticholic acid), inhibitors of de novo lipogenesis (aramchol, NDI-010976), incretins (liraglutide) and fibroblast growth factor (FGF)-21 or FGF-19 analogues. A second approach is targeting the oxidative stress, inflammation and injury that follow the metabolic stress. Medications from this group include antioxidants (vitamin E), medications with a target in the tumour necrosis factor α pathway (emricasan, pentoxifylline) and immune modulators (amlexanox, cenicriviroc). A third group has a target in the gut, including antiobesity agents such as orlistat or gut microbiome modulators (IMM-124e, faecal microbial transplant, solithromycin). Finally, as the ongoing injury leads to fibrosis, the harbinger of liver-related morbidity and mortality, antifibrotics (simtuzumab and GR-MD-02) will be an important element of therapy. It is very likely that in the next few years several medications will be available to clinicians treating patients with NAFLD across the entire spectrum of disease.}, }
@article {pmid27644000, year = {2016}, author = {Goeser, F and Schlabe, S and Ruiner, CE and Kramer, L and Strassburg, CP and Spengler, U}, title = {Non-invasive fecal microbiota transplantation for recurrent Clostridium difficile infection in a patient presenting with hypertensive disorder post interventionem.}, journal = {Zeitschrift fur Gastroenterologie}, volume = {54}, number = {10}, pages = {1143-1146}, doi = {10.1055/s-0042-110795}, pmid = {27644000}, issn = {1439-7803}, mesh = {Aged, 80 and over ; *Clostridioides difficile ; *Enteral Nutrition ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*therapy ; Equipment Design ; Equipment Failure Analysis ; Fecal Microbiota Transplantation/adverse effects/*instrumentation/*methods ; Humans ; Hypertension/diagnosis/*etiology/prevention &amp; control ; Male ; Recurrence ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation has gathered much attention due to its high efficacy in resolving recurrent Clostridium difficile infection. Until today, it is recognized as a safe procedure without any severe side effects. Patients with impaired conscious states suffering from recurrent episodes of aspiration are at increased risk by endoscopic interventions needed during standard approaches for fecal microbiota transplantation application.Here, we illustrate the case of a tetraplegic patient undergoing fecal microbiota transplantation due to his fifth recurrent episode of Clostridium difficile infection using a self-advancing nasal jejunal feeding tube as effective minimal-invasive option of fecal microbiota transplantation application. Persistent aggravation of arterial hypertension, which developed post-intervention in this patient, could be interpreted as a hitherto unknown side effect of fecal microbiota transplantation in this setting. Moreover, this is a further hint for a link between the intestinal microbiome and arterial hypertension in general.}, }
@article {pmid27643493, year = {2016}, author = {Terveer, EM and van Beurden, YH and Kuijper, EJ and Keller, JJ}, title = {[Fecal microbiota transplantation, a novel therapy for recurrent Clostridium difficile infection].}, journal = {Nederlands tijdschrift voor tandheelkunde}, volume = {123}, number = {9}, pages = {406-409}, doi = {10.5177/ntvt.2016.09.16146}, pmid = {27643493}, issn = {0028-2200}, mesh = {Anti-Bacterial Agents ; *Clostridioides difficile ; Clostridium Infections/prevention &amp; control/*therapy ; *Fecal Microbiota Transplantation/methods ; Feces ; Humans ; }, abstract = {Clostridium difficile infection is caused by a disturbance of the gut microbiota, often resulting from the use of antibiotics. Among a sub group of patients with this disorder, treatment with antibiotics is not effective. They develop a chronic, recurrent infection. Such patients can be treated with a fecal microbiota transplantation (FMT), or fecal transplantation. The crucial steps for safe application of fecal transplantation are central donor selection and screening. To optimise safety and to guarantee the availability of donor feces for fecal transplantation, the Nederlandse Donor Feces Bank (Dutch Donor Feces Bank) was established. At this facility, ready-to-use, screened donor feces can be ordered for patients with (recurrent) Clostridium difficile infections, who can then be treated at their own hospital.}, }
@article {pmid27640125, year = {2016}, author = {Crespo-Salgado, J and Vehaskari, VM and Stewart, T and Ferris, M and Zhang, Q and Wang, G and Blanchard, EE and Taylor, CM and Kallash, M and Greenbaum, LA and Aviles, DH}, title = {Intestinal microbiota in pediatric patients with end stage renal disease: a Midwest Pediatric Nephrology Consortium study.}, journal = {Microbiome}, volume = {4}, number = {1}, pages = {50}, pmid = {27640125}, issn = {2049-2618}, support = {G12 MD007595/MD/NIMHD NIH HHS/United States ; }, mesh = {Actinobacteria/isolation &amp; purification ; Adolescent ; Bacterial Load ; Bacteroidetes/isolation &amp; purification ; C-Reactive Protein/metabolism ; Child ; Child, Preschool ; Cresols/*blood ; Feces/microbiology ; Female ; Firmicutes/isolation &amp; purification ; Gastrointestinal Microbiome/*genetics ; Humans ; Indican/*blood ; Intestines/microbiology ; Kidney Failure, Chronic/*microbiology ; Kidney Transplantation ; Lactic Acid/blood ; Male ; Peritoneal Dialysis ; Proteobacteria/isolation &amp; purification ; RNA, Ribosomal, 16S/genetics ; Sulfuric Acid Esters/*blood ; Uremia/*blood ; Verrucomicrobia/isolation &amp; purification ; }, abstract = {BACKGROUND: End-stage renal disease (ESRD) is associated with uremia and increased systemic inflammation. Alteration of the intestinal microbiota may facilitate translocation of endotoxins into the systemic circulation leading to inflammation. We hypothesized that children with ESRD have an altered intestinal microbiota and increased serum levels of bacterially derived uremic toxins.<br><br>METHODS: Four groups of subjects were recruited: peritoneal dialysis (PD), hemodialysis (HD), post-kidney transplant and healthy controls. Stool bacterial composition was assessed by pyrosequencing analysis of 16S rRNA genes. Serum levels of C-reactive protein (CRP), D-lactate, p-cresyl sulfate and indoxyl sulfate were measured.<br><br>RESULTS: Compared to controls, the relative abundance of Firmicutes (P&#x2009;=&#x2009;0.0228) and Actinobacteria (P&#x2009;=&#x2009;0.0040) was decreased in PD patients. The relative abundance of Bacteroidetes was increased in HD patients (P&#x2009;=&#x2009;0.0462). Compared to HD patients the relative abundance of Proteobacteria (P&#x2009;=&#x2009;0.0233) was increased in PD patients. At the family level, Enterobacteriaceae was significantly increased in PD patients (P&#x2009;=&#x2009;0.0020) compared to controls; whereas, Bifidobacteria showed a significant decrease in PD and transplant patients (P&#x2009;=&#x2009;0.0020) compared to control. Alpha diversity was decreased in PD patients and kidney transplant using both phylogenetic and non-phylogenetic diversity measures (P&#x2009;=&#x2009;0.0031 and 0.0003, respectively), while beta diversity showed significant separation (R statistic&#x2009;=&#x2009;0.2656, P&#x2009;=&#x2009;0.010) between PD patients and controls. ESRD patients had increased serum levels of p-cresyl sulfate and indoxyl sulfate (P&#x2009;<&#x2009;0.0001 and P&#x2009;<&#x2009;0.0001, respectively). The data suggests that no significant correlation exists between the alpha diversity of the intestinal microbiota and CRP, D-lactate, or uremic toxins. Oral iron supplementation results in expansion of the phylum Proteobacteria.<br><br>CONCLUSIONS: Children with ESRD have altered intestinal microbiota and increased bacterially derived serum uremic toxins.}, }
@article {pmid27639987, year = {2017}, author = {Ait Said, K and Leroux, Y and Menahem, B and Doerfler, A and Alves, A and Tillou, X}, title = {Effect of bariatric surgery on urinary and fecal incontinence: prospective analysis with 1-year follow-up.}, journal = {Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery}, volume = {13}, number = {2}, pages = {305-312}, doi = {10.1016/j.soard.2016.08.019}, pmid = {27639987}, issn = {1878-7533}, mesh = {Aftercare ; Analysis of Variance ; *Bariatric Surgery ; Body Mass Index ; Dyslipidemias/complications ; Fecal Incontinence/*surgery ; Female ; Humans ; Hypertension/complications ; Male ; Middle Aged ; Obesity, Morbid/complications/surgery ; Postoperative Care ; Prospective Studies ; Quality of Life ; Surveys and Questionnaires ; Treatment Outcome ; Urinary Incontinence/*surgery ; }, abstract = {BACKGROUND: Few studies have established that obesity promotes all types of urinary incontinence and disorders of the pelvic floor. The role of bariatric surgery in urinary incontinence remains poorly studied.<br><br>OBJECTIVE: To determine the effect of bariatric surgery on urinary incontinence, dysuria, and fecal incontinence before and 1 year after bariatric surgery.<br><br>SETTING: University hospital expert in bariatric surgery METHODS: This was an observational cohort study of 140 patients who underwent bariatric surgery between September 2013 and September 2014. Patients prospectively completed 4 questionnaires, 2 for urinary symptoms and 2 for fecal incontinence. Eighty-three women and 33 men completed 4 questionnaires the day before surgery when arriving in the department and 1 year after surgery.<br><br>RESULTS: Of the 140 patients, 116 completely responded to the 4 questionnaires. The rate of urinary incontinence was 50.9% before surgery and 19% at 1-year follow-up (P<.0001). After bariatric surgery, there was improvement in the rate of stress urinary incontinence: 39.7% before surgery versus 15.5% at 1 year (P<.0001). In addition, there was an improvement in urinary urge incontinence: 36.8% versus 7.9% at 1 year (P<.0001). The dysuria rate was 19.8% before surgery versus 3.4% at 1 year (P<.0001). Bariatric surgery improved the quality of life related to urinary symptoms (P<.0001). One year after surgery, there was no significant difference in terms of prevalence and severity of fecal incontinence.<br><br>CONCLUSION: We confirmed with our study that weight loss after bariatric surgery improves stress urinary incontinence, urge incontinence, dysuria, and quality of life. However, we did not find any positive effect on fecal incontinence.}, }
@article {pmid27639802, year = {2017}, author = {Wang, Y and Huang, D and Chen, KY and Cui, M and Wang, W and Huang, X and Awadellah, A and Li, Q and Friedman, A and Xin, WW and Di Martino, L and Cominelli, F and Miron, A and Chan, R and Fox, JG and Xu, Y and Shen, X and Kalady, MF and Markowitz, S and Maillard, I and Lowe, JB and Xin, W and Zhou, L}, title = {Fucosylation Deficiency in Mice Leads to Colitis and Adenocarcinoma.}, journal = {Gastroenterology}, volume = {152}, number = {1}, pages = {193-205.e10}, pmid = {27639802}, issn = {1528-0012}, support = {K08 HL089218/HL/NHLBI NIH HHS/United States ; R01 AI091627/AI/NIAID NIH HHS/United States ; P30 DK097948/DK/NIDDK NIH HHS/United States ; R01 GM114254/GM/NIGMS NIH HHS/United States ; R01 GM095990/GM/NIGMS NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; R01 DK055812/DK/NIDDK NIH HHS/United States ; R01 HL103827/HL/NHLBI NIH HHS/United States ; }, mesh = {Adenocarcinoma/chemistry/*etiology/pathology ; Adult ; Aged ; Aged, 80 and over ; Animals ; Bone Marrow Transplantation ; Carbohydrate Epimerases/*deficiency/genetics ; Carcinogenesis ; Cecum/pathology ; Cell Proliferation ; Colitis/*etiology/*metabolism/pathology/prevention &amp; control ; Colon/*metabolism/pathology ; Colonic Neoplasms/chemistry/*etiology/pathology ; Cytokines/genetics/metabolism ; Feces/microbiology ; Female ; Fucose/administration &amp; dosage ; Gastrointestinal Microbiome ; Guanosine Diphosphate Fucose/biosynthesis/deficiency ; Humans ; Intestinal Mucosa/*metabolism ; Ketone Oxidoreductases/*deficiency/genetics ; Male ; Mice ; Mice, Knockout ; Middle Aged ; Permeability ; RNA, Messenger/metabolism ; Receptor, Notch1/metabolism ; Receptor, Notch2/metabolism ; Signal Transduction ; Transcription Factor HES-1/analysis/metabolism ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: De novo synthesis of guanosine diphosphate (GDP)-fucose, a substrate for fucosylglycans, requires sequential reactions mediated by GDP-mannose 4,6-dehydratase (GMDS) and GDP-4-keto-6-deoxymannose 3,5-epimerase-4-reductase (FX or tissue specific transplantation antigen P35B [TSTA3]). GMDS deletions and mutations are found in 6%-13% of colorectal cancers; these mostly affect the ascending and transverse colon. We investigated whether a lack of fucosylation consequent to loss of GDP-fucose synthesis contributes to colon carcinogenesis.<br><br>METHODS: FX deficiency and GMDS deletion produce the same biochemical phenotype of GDP-fucose deficiency. We studied a mouse model of fucosylation deficiency (Fx-/- mice) and mice with the full-length Fx gene (controls). Mice were placed on standard chow or fucose-containing diet (equivalent to a control fucosylglycan phenotype). Colon tissues were collected and analyzed histologically or by enzyme-linked immunosorbent assays to measure cytokine levels; T cells also were collected and analyzed. Fecal samples were analyzed by 16s ribosomal RNA sequencing. Mucosal barrier function was measured by uptake of fluorescent dextran. We transplanted bone marrow cells from Fx-/- or control mice (Ly5.2) into irradiated 8-week-old Fx-/- or control mice (Ly5.1). We performed immunohistochemical analyses for expression of Notch and the hes family bHLH transcription factor (HES1) in colon tissues from mice and a panel of 60 human colorectal cancer specimens (27 left-sided, 33 right-sided).<br><br>RESULTS: Fx-/- mice developed colitis and serrated-like lesions. The intestinal pathology of Fx-/- mice was reversed by addition of fucose to the diet, which restored fucosylation via a salvage pathway. In the absence of fucosylation, dysplasia appeared and progressed to adenocarcinoma in up to 40% of mice, affecting mainly the right colon and cecum. Notch was not activated in Fx-/- mice fed standard chow, leading to decreased expression of its target Hes1. Fucosylation deficiency altered the composition of the fecal microbiota, reduced mucosal barrier function, and altered epithelial proliferation marked by Ki67. Fx-/- mice receiving control bone marrow cells had intestinal inflammation and dysplasia, and reduced expression of cytokines produced by&#xa0;cytotoxic T cells. Human sessile serrated adenomas and right-sided colorectal tumors with epigenetic loss of MutL homolog 1 (MLH1) had lost or&#xa0;had lower levels of HES1 than other colorectal tumor types or&#xa0;nontumor tissues.<br><br>CONCLUSIONS: In mice, fucosylation deficiency leads to colitis and adenocarcinoma, loss of Notch activation, and down-regulation of Hes1. HES1 loss correlates with the development of human right-sided colorectal tumors with epigenetic loss of MLH1. These findings indicate that carcinogenesis in a subset of colon cancer is consequent to a molecular mechanism driven by fucosylation deficiency and/or HES1-loss.}, }
@article {pmid27634282, year = {2017}, author = {Ba, Q and Li, M and Chen, P and Huang, C and Duan, X and Lu, L and Li, J and Chu, R and Xie, D and Song, H and Wu, Y and Ying, H and Jia, X and Wang, H}, title = {Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice.}, journal = {Environmental health perspectives}, volume = {125}, number = {3}, pages = {437-446}, pmid = {27634282}, issn = {1552-9924}, mesh = {*Adiposity ; Animals ; Cadmium/*toxicity ; Gastrointestinal Microbiome/*drug effects ; Hazardous Substances/*toxicity ; Lipid Metabolism ; Liver/metabolism ; Mice ; Obesity/metabolism ; }, abstract = {BACKGROUND: Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear.<br><br>OBJECTIVES: We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action.<br><br>METHODS: We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms.<br><br>RESULTS: Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice.<br><br>CONCLUSIONS: An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437-446;&#x2002;http://dx.doi.org/10.1289/EHP360.}, }
@article {pmid27633598, year = {2016}, author = {Kerman, DH}, title = {Endoscopic Delivery of Fecal Biotherapy in Inflammatory Bowel Disease.}, journal = {Gastrointestinal endoscopy clinics of North America}, volume = {26}, number = {4}, pages = {707-717}, doi = {10.1016/j.giec.2016.06.006}, pmid = {27633598}, issn = {1558-1950}, mesh = {Dysbiosis/complications/*surgery ; Endoscopy, Gastrointestinal/*methods ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*surgery ; }, abstract = {The intestinal microbiome plays an important role in the pathogenesis of inflammatory bowel disease (IBD). We are able to use the microbiome as a therapeutic target with use of fecal microbiota transplantation (FMT) for cure of recurrent Clostridium difficile infection. Given our ability to target the dysbiotic state with FMT, its use as therapy in IBD has tremendous potential. This overview discusses the practical considerations of FMT therapy with respect to our current understanding of safety and efficacy in IBD, screening for donors and recipients, specimen handling and storage, methods of delivery, and regulatory considerations.}, }
@article {pmid27633134, year = {2016}, author = {Muñoz-Garach, A and Diaz-Perdigones, C and Tinahones, FJ}, title = {Gut microbiota and type 2 diabetes mellitus.}, journal = {Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion}, volume = {63}, number = {10}, pages = {560-568}, doi = {10.1016/j.endonu.2016.07.008}, pmid = {27633134}, issn = {1579-2021}, mesh = {Adipose Tissue, Brown/metabolism ; Bacterial Physiological Phenomena ; Butyrates/metabolism ; Diabetes Mellitus, Type 2/etiology/*microbiology/therapy ; Disease Susceptibility ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Incretins/metabolism ; Insulin Resistance ; Insulin-Secreting Cells/metabolism ; Metabolic Syndrome/metabolism/microbiology ; Microbiota ; Obesity/etiology/microbiology ; Prebiotics ; Probiotics ; Species Specificity ; }, abstract = {In recent years, many studies have related gut microbiome to development of highly prevalent diseases such as type 2 diabetes and obesity. Obesity itself is associated to changes in the composition of gut microbiome, with a trend to an overgrowth of microorganisms more efficiently obtaining energy from diet. There are several mechanisms that relate microbiota to the onset of insulin resistance and diabetes, including changes in bowel permeability, endotoxemia, interaction with bile acids, changes in the proportion of brown adipose tissue, and effects associated to use of drugs like metformin. Currently, use of pro and prebiotics and other new techniques such as gut microbiota transplant, or even antibiotic therapy, has been postulated to be useful tools to modulate the development of obesity and insulin resistance through the diet.}, }
@article {pmid27621567, year = {2016}, author = {Gallo, A and Passaro, G and Gasbarrini, A and Landolfi, R and Montalto, M}, title = {Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate.}, journal = {World journal of gastroenterology}, volume = {22}, number = {32}, pages = {7186-7202}, pmid = {27621567}, issn = {2219-2840}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Diarrhea/etiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology/*therapy ; Irritable Bowel Syndrome/microbiology/therapy ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; Rotavirus Infections/therapy ; }, abstract = {Alterations of intestinal microflora may significantly contribute to the pathogenesis of different inflammatory and autoimmune disorders. There is emerging interest on the role of selective modulation of microflora in inducing benefits in inflammatory intestinal disorders, by as probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). To summarize recent evidences on microflora modulation in main intestinal inflammatory disorders, PubMed was searched using terms microbiota, intestinal flora, probiotics, prebiotics, fecal transplantation. More than three hundred articles published up to 2015 were selected and reviewed. Randomized placebo-controlled trials and meta-analysis were firstly included, mainly for probiotics. A meta-analysis was not performed because of the heterogeneity of these studies. Most of relevant data derived from studies on probiotics, reporting some efficacy in ulcerative colitis and in pouchitis, while disappointing results are available for Crohn's disease. Probiotic supplementation may significantly reduce rates of rotavirus diarrhea. Efficacy of probiotics in NSAID enteropathy and irritable bowel syndrome is still controversial. Finally, FMT has been recently recognized as an efficacious treatment for recurrent Clostridium difficile infection. Modulation of intestinal flora represents a very interesting therapeutic target, although it still deserves some doubts and limitations. Future studies should be encouraged to provide new understanding about its therapeutical role.}, }
@article {pmid27620005, year = {2017}, author = {Ghosh, N and Malik, FA and Daver, RG and Vanichanan, J and Okhuysen, PC}, title = {Viral associated diarrhea in immunocompromised and cancer patients at a large comprehensive cancer center: a 10-year retrospective study.}, journal = {Infectious diseases (London, England)}, volume = {49}, number = {2}, pages = {113-119}, doi = {10.1080/23744235.2016.1224384}, pmid = {27620005}, issn = {2374-4243}, mesh = {Adenoviridae/*isolation &amp; purification ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Diarrhea/*epidemiology/pathology/virology ; Feces/virology ; Female ; Humans ; *Immunocompromised Host ; Male ; Middle Aged ; Neoplasms/*complications ; Norovirus/*isolation &amp; purification ; Retrospective Studies ; Rotavirus/*isolation &amp; purification ; Seasons ; United States/epidemiology ; Virus Diseases/*epidemiology/pathology/virology ; Young Adult ; }, abstract = {BACKGROUND: Viral associated diarrhea (VAD) due to Norovirus (NV), Rotavirus (RV) and Adenovirus (AV) is common in immunocompromised and cancer patients. We sought to determine if the clinical characteristics, morbidity and seasonality of infection differed according to the type of enteric virus identified.<br><br>METHODS: Cases of NV, RV and AV were identified in stool specimens submitted to the clinical microbiology laboratory between November 2005 and February 2015. Clinical characteristics of patients, potential risk factors and outcomes were compared.<br><br>RESULTS: A total of 97 VAD cases were identified: NV (n&#x2009;=&#x2009;49), RV (n&#x2009;=&#x2009;34) and AV (n&#x2009;=&#x2009;14). The majority of cases were in patients with leukemia and lymphoma. NV (59%), RV (74%) and AV (78%) were identified in hematopoietic stem cell transplant (HSCT) recipients; and in patients with graft versus host disease (GVHD): NV (34%), RV (46%) and AV (57%). Nine cases of NV were genotyped; all were due to genotype II. Nine of 49 (18%) cases of NV, 7 of 34 (20%) cases of RV and 2 of 14 (14%) cases of AV were considered to be health care acquired (HCA). In multivariate analysis, immunosuppression (OR 2.8 95% CI 1.26-6.60, p&#x2009;=&#x2009;.01) and neutropenia (OR 4.8 95% CI 1.27-18.5, p&#x2009;=&#x2009;.01) were identified as risk factors for NV diarrhea compared to RV and AV.<br><br>CONCLUSIONS: In our study, agents responsible for VAD occurred year round but predominated in the winter time; caused prolonged illness and were frequently health care associated. Presentations were atypical in many cases without upper gastrointestinal symptoms such as nausea and vomiting.}, }
@article {pmid27609178, year = {2016}, author = {Youngster, I and Mahabamunuge, J and Systrom, HK and Sauk, J and Khalili, H and Levin, J and Kaplan, JL and Hohmann, EL}, title = {Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection.}, journal = {BMC medicine}, volume = {14}, number = {1}, pages = {134}, pmid = {27609178}, issn = {1741-7015}, support = {UL1 TR000170/TR/NCATS NIH HHS/United States ; }, mesh = {Administration, Oral ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Capsules ; Child ; Clostridioides difficile ; Clostridium Infections/*therapy ; Drug Resistance, Bacterial ; Feasibility Studies ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Freezing ; Humans ; Male ; Microbiota ; Middle Aged ; Pilot Projects ; Recurrence ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to be safe and effective in treating refractory or relapsing C. difficile infection (CDI), but its use has been limited by practical barriers. We recently reported a small preliminary feasibility study using orally administered frozen fecal capsules. Following these early results, we now report our clinical experience in a large cohort with structured follow-up.<br><br>METHODS: We prospectively followed a cohort of patients with recurrent or refractory CDI who were treated with frozen, encapsulated FMT at our institution. The primary endpoint was defined as clinical resolution whilst off antibiotics for CDI at 8&#xa0;weeks after last capsule ingestion. Safety was defined as any FMT-related adverse event grade 2 or above.<br><br>RESULTS: Overall, 180 patients aged 7-95 years with a minimal follow-up of 8&#xa0;weeks were included in the analysis. CDI resolved in 82&#xa0;% of patients after a single treatment, rising to a 91&#xa0;% cure rate with two treatments. Three adverse events Grade 2 or above, deemed related or possibly related to FMT, were observed.<br><br>CONCLUSIONS: We confirm the effectiveness and safety of oral administration of frozen encapsulated fecal material, prepared from unrelated donors, in treating recurrent CDI. Randomized studies and FMT registries are still needed to ascertain long-term safety.}, }
@article {pmid27607336, year = {2016}, author = {Ward, NL and Phillips, CD and Nguyen, DD and Shanmugam, NK and Song, Y and Hodin, R and Shi, HN and Cherayil, BJ and Goldstein, AM}, title = {Antibiotic Treatment Induces Long-lasting Changes in the Fecal Microbiota that Protect Against Colitis.}, journal = {Inflammatory bowel diseases}, volume = {22}, number = {10}, pages = {2328-2340}, pmid = {27607336}, issn = {1536-4844}, support = {K08 DK083430/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 AI089700/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Colitis/chemically induced/*microbiology/prevention &amp; control ; Dextran Sulfate ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome/*drug effects ; Intestinal Mucosa/microbiology ; Mice ; Mice, Inbred C57BL ; Mucous Membrane/microbiology ; Severity of Illness Index ; T-Lymphocytes/drug effects/microbiology ; }, abstract = {BACKGROUND: The interplay between host genetics, immunity, and microbiota is central to the pathogenesis of inflammatory bowel disease. Previous population-based studies suggested a link between antibiotic use and increased inflammatory bowel disease risk, but the mechanisms are unknown. The purpose of this study was to determine the long-term effects of antibiotic administration on microbiota composition, innate immunity, and susceptibility to colitis, as well as the mechanism by which antibiotics alter host colitogenicity.<br><br>METHODS: Wild-type mice were given broad-spectrum antibiotics or no antibiotics for 2 weeks, and subsequent immunophenotyping and 16S rRNA gene sequencing-based analysis of the fecal microbiome were performed 6 weeks later. In a separate experiment, control and antibiotic-treated mice were given 7 days of dextran sulfate sodium, 6 weeks after completing antibiotic treatment, and the severity of colitis scored histologically. Fecal transfer was performed from control or antibiotic-treated mice to recipient mice whose endogenous microbiota had been cleared with antibiotics, and the susceptibility of the recipients to dextran sulfate sodium-induced colitis was analyzed. Naive CD4 T cells were transferred from control and antibiotic-treated mice to immunodeficient Rag-1 recipients and the severity of colitis compared.<br><br>RESULTS: Antibiotics led to sustained dysbiosis and changes in T-cell subpopulations, including reductions in colonic lamina propria total T cells and CD4 T cells. Antibiotics conferred protection against dextran sulfate sodium colitis, and this effect was transferable by fecal transplant but not by naive T cells.<br><br>CONCLUSIONS: Antibiotic exposure protects against colitis, and this effect is transferable with fecal microbiota from antibiotic-treated mice, supporting a protective effect of the microbial community.}, }
@article {pmid27606976, year = {2016}, author = {Hebbard, AI and Slavin, MA and Reed, C and Teh, BW and Thursky, KA and Trubiano, JA and Worth, LJ}, title = {The epidemiology of Clostridium difficile infection in patients with cancer.}, journal = {Expert review of anti-infective therapy}, volume = {14}, number = {11}, pages = {1077-1085}, doi = {10.1080/14787210.2016.1234376}, pmid = {27606976}, issn = {1744-8336}, mesh = {Adult ; Aminoglycosides/administration &amp; dosage/therapeutic use ; Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; Bacteriological Techniques ; Clostridioides difficile/drug effects/*isolation &amp; purification ; Drug Utilization/standards ; Enterocolitis, Pseudomembranous/*epidemiology/microbiology/therapy ; Fecal Microbiota Transplantation ; Fidaxomicin ; Humans ; Neoplasms/drug therapy/epidemiology/*microbiology ; Risk Factors ; }, abstract = {Clostridium difficile infection (CDI) is a significant cause of healthcare-associated diarrhoea, and the emergence of endemic strains resulting in poorer outcomes is recognised worldwide. Patients with cancer are a specific high-risk group for development of infection. Areas covered: In this review, modifiable and non-modifiable risk factors for CDI in adult patients with haematological malignancy or solid tumours are evaluated. In particular, the contribution of antimicrobial exposure, hospitalisation and gastric acid suppression to risk of CDI are discussed. Recent advances in CDI treatment are outlined, namely faecal microbiota transplantation and fidaxomicin therapy for severe/refractory infection in cancer populations. Outcomes of CDI, including mortality are presented, together with the need for valid severity rating tools customised for cancer populations. Expert commentary: Future areas for research include the prognostic value of C. difficile colonisation in cancer patients and the potential impact of dedicated antimicrobial stewardship programs in reducing the burden of CDI in cancer units.}, }
@article {pmid27580384, year = {2016}, author = {Fischer, M and Kao, D and Kelly, C and Kuchipudi, A and Jafri, SM and Blumenkehl, M and Rex, D and Mellow, M and Kaur, N and Sokol, H and Cook, G and Hamilton, MJ and Phelps, E and Sipe, B and Xu, H and Allegretti, JR}, title = {Fecal Microbiota Transplantation is Safe and Efficacious for Recurrent or Refractory Clostridium difficile Infection in Patients with Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {22}, number = {10}, pages = {2402-2409}, doi = {10.1097/MIB.0000000000000908}, pmid = {27580384}, issn = {1536-4844}, mesh = {Adult ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: New treatments are needed as Clostridium difficile infection (CDI) is becoming increasingly formidable. Fecal microbiota transplantation (FMT) has a 90% success rate in the treatment of recurrent CDI. However, evidence regarding its safety, efficacy, and effect on disease activity in patients with inflammatory bowel disease (IBD) is lacking.<br><br>METHODS: This cohort study used data from 8 national and international academic centers. Patients with established IBD who underwent FMT for recurrent CDI were followed for a minimum of 3 months. The primary outcome was CDI recurrence at 3 months after FMT. The secondary outcomes were (1) IBD activity and severity at 3 months based on the judgment of the treating physician, endoscopic findings, and clinical disease activity scores; and (2) safety.<br><br>RESULTS: Sixty-seven patients were included in the analysis. Thirty-five (52%) had Crohn's disease, 31 (46%) ulcerative colitis, and one indeterminate colitis with 43 (64%) patients on an immunosuppressive agent at the time of FMT. The initial FMT was successful in 53 (79%) patients. After the FMT, IBD disease activity was reported as improved in 25 (37%), no change in 20 (30%), and worse in 9 (13%) patients. Serious adverse events included colectomy (1.4%), hospitalization for CDI (2.9%), hospitalization for IBD flare (2.9%), small bowel obstruction (1.4%), CMV colitis (1.4%), and pancreatitis (1.4%).<br><br>DISCUSSION: The overall CDI cure rates were high, with a large percentage of patients experiencing clinical improvement of their IBD after FMT. A minority of patients developed an IBD flare. No severe adverse events directly attributable to FMT were found in this largest reported series of recurrent or refractory CDI patients with concurrent IBD.}, }
@article {pmid27577172, year = {2016}, author = {Rabot, S and Membrez, M and Blancher, F and Berger, B and Moine, D and Krause, L and Bibiloni, R and Bruneau, A and Gérard, P and Siddharth, J and Lauber, CL and Chou, CJ}, title = {High fat diet drives obesity regardless the composition of gut microbiota in mice.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {32484}, pmid = {27577172}, issn = {2045-2322}, mesh = {Animals ; Bacteroidetes/classification/growth &amp; development ; *Diet, High-Fat ; Dietary Fats/*adverse effects ; Fecal Microbiota Transplantation ; Firmicutes/classification/growth &amp; development ; Gastrointestinal Microbiome/physiology ; Glucose Intolerance/etiology/*metabolism/microbiology/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/etiology/*metabolism/microbiology/pathology ; Proteobacteria/classification/growth &amp; development ; }, abstract = {The gut microbiota is involved in many aspects of host physiology but its role in body weight and glucose metabolism remains unclear. Here we studied the compositional changes of gut microbiota in diet-induced obesity mice that were conventionally raised or received microbiota transplantation. In conventional mice, the diversity of the faecal microbiota was weakly associated with 1(st) week weight gain but transferring the microbiota of mice with contrasting weight gain to germfree mice did not change obesity development or feed efficiency of recipients regardless whether the microbiota was taken before or after 10 weeks high fat (HF) feeding. Interestingly, HF-induced glucose intolerance was influenced by microbiota inoculation and improved glucose tolerance was associated with a low Firmicutes to Bacteroidetes ratio. Transplantation of Bacteroidetes rich microbiota compared to a control microbiota ameliorated glucose intolerance caused by HF feeding. Altogether, our results demonstrate that gut microbiota is involved in the regulation of glucose metabolism and the abundance of Bacteroidetes significantly modulates HF-induced glucose intolerance but has limited impact on obesity in mice. Our results suggest that gut microbiota is a part of complex aetiology of insulin resistance syndrome, individual microbiota composition may cause phenotypic variation associated with HF feeding in mice.}, }
@article {pmid27573580, year = {2016}, author = {Abt, MC and McKenney, PT and Pamer, EG}, title = {Clostridium difficile colitis: pathogenesis and host defence.}, journal = {Nature reviews. Microbiology}, volume = {14}, number = {10}, pages = {609-620}, pmid = {27573580}, issn = {1740-1534}, support = {K99 AI125786/AI/NIAID NIH HHS/United States ; T32 CA009149/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Bacterial Toxins/metabolism ; Bile Acids and Salts/metabolism ; Clostridioides difficile/genetics/growth &amp; development/*pathogenicity/physiology ; Colitis/immunology/*microbiology/physiopathology/therapy ; Enterocolitis, Pseudomembranous/immunology/*microbiology/physiopathology/therapy ; Fecal Microbiota Transplantation ; *Host-Pathogen Interactions ; Humans ; Microbiota/*physiology ; Spores, Bacterial/chemistry/genetics/physiology ; Virulence Factors/genetics ; }, abstract = {Clostridium difficile is a major cause of intestinal infection and diarrhoea in individuals following antibiotic treatment. Recent studies have begun to elucidate the mechanisms that induce spore formation and germination and have determined the roles of C. difficile toxins in disease pathogenesis. Exciting progress has also been made in defining the role of the microbiome, specific commensal bacterial species and host immunity in defence against infection with C. difficile. This Review will summarize the recent discoveries and developments in our understanding of C. difficile infection and pathogenesis.}, }
@article {pmid27572174, year = {2016}, author = {Sadowsky, MJ and Khoruts, A}, title = {Faecal microbiota transplantation is promising but not a panacea.}, journal = {Nature microbiology}, volume = {1}, number = {}, pages = {16015}, pmid = {27572174}, issn = {2058-5276}, mesh = {Animals ; Clostridioides difficile ; Clostridium Infections/*therapy ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid27567309, year = {2016}, author = {De la Torre, L and Cogley, K and Calisto, JL and Santos, K and Ruiz, A and Zornoza, M}, title = {Vaginal agenesis and rectovestibular fistula. Experience utilizing distal ileum for the vaginal replacement in these patients, preserving the natural fecal reservoir.}, journal = {Journal of pediatric surgery}, volume = {51}, number = {11}, pages = {1871-1876}, doi = {10.1016/j.jpedsurg.2016.08.003}, pmid = {27567309}, issn = {1531-5037}, mesh = {*Abnormalities, Multiple ; Anal Canal/abnormalities/*surgery ; Child ; Child, Preschool ; Congenital Abnormalities/diagnosis/*surgery ; Cross-Sectional Studies ; Defecation ; Female ; Humans ; Ileum/*transplantation ; Infant ; Infant, Newborn ; Plastic Surgery Procedures/*methods ; Rectovaginal Fistula/diagnosis/physiopathology/*surgery ; Retrospective Studies ; Vagina/*abnormalities/*surgery ; }, abstract = {BACKGROUND: The association of rectovestibular fistula (RVF) and vaginal agenesis (VA) presents a diagnostic and management challenge. The vaginal replacement is usually performed with rectum or sigmoid, which are the natural fecal reservoirs; thus, the fecal control could be affected. We present our experience utilizing ileum to preserve the rectum and sigmoid.<br><br>METHODS: We performed a retrospective study of eight patients with RVF and VA treated from May 2011 to June 2015 at two colorectal centers, at Pittsburgh and Mexico. We recorded the age at diagnosis of VA, treatment, presence of other associated malformations and outcome.<br><br>RESULTS: Eight of forty-nine girls with RVF had an associated VA (16.3%). Three patients had a timely diagnosis and five a delayed diagnosis. Six patients were submitted to a vaginal replacement with ileum and achieved fecal control. Two are waiting for surgery.<br><br>CONCLUSIONS: A high index of suspicion of vaginal agenesis helps in a timely diagnosis in girls with RVF. The use of ileum allows for preservation of the fecal reservoirs, thus optimizing the chance for fecal control in patients with anorectal malformations.}, }
@article {pmid27559357, year = {2016}, author = {Kulecka, M and Paziewska, A and Zeber-Lubecka, N and Ambrozkiewicz, F and Kopczynski, M and Kuklinska, U and Pysniak, K and Gajewska, M and Mikula, M and Ostrowski, J}, title = {Prolonged transfer of feces from the lean mice modulates gut microbiota in obese mice.}, journal = {Nutrition &amp; metabolism}, volume = {13}, number = {1}, pages = {57}, pmid = {27559357}, issn = {1743-7075}, abstract = {BACKGROUND: Transplanting a fecal sample from lean, healthy donors to obese recipients has been shown to improve metabolic syndrome symptoms. We therefore examined the gut microbiota in mice after administering a long-term, high-fat diet (HFD) supplemented with feces from lean mice through the fecal-oral route.<br><br>METHODS: C57BL6/W mice were allowed to adapt to a non-specific pathogen free (SFP) environment for 2&#xa0;weeks before being divided into three groups of 16 animals. Animals were fed for 28&#xa0;weeks with a normal diet (ND), HFD or HFD supplemented with feces from ND-fed mice (HFDS). The composition of colonizing bacteria was evaluated in droppings collected under SPF conditions at the beginning of the study and at 12 and 28&#xa0;weeks using an 16S Metagenomics Kit on Ion PGM sequencer.<br><br>RESULTS: HFD and HFDS-fed mice attained (p&#x2009;<&#x2009;0.05) greater body weights by weeks 6 and 5, respectively. HFDS-fed mice gained more weight than HFD-fed mice by week 25. Both species diversity and richness indices increased with time in HFDS mice only.<br><br>CONCLUSIONS: Prolonged HFD-fed mice supplementation with feces from lean mice altered bacteria species diversity and richness, accelerated the onset of obesity, and caused increased weight gain in the later weeks of the HFD regimen.}, }
@article {pmid27558248, year = {2016}, author = {Mayor, S}, title = {Donor faecal transplantation is highly curative in recurrent C difficile infection, trial finds.}, journal = {BMJ (Clinical research ed.)}, volume = {354}, number = {}, pages = {i4638}, doi = {10.1136/bmj.i4638}, pmid = {27558248}, issn = {1756-1833}, mesh = {Clostridioides difficile ; *Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid27556065, year = {2016}, author = {Peng, Z and Xiang, J and He, Z and Zhang, T and Xu, L and Cui, B and Li, P and Huang, G and Ji, G and Nie, Y and Wu, K and Fan, D and Zhang, F}, title = {Colonic transendoscopic enteral tubing: A novel way of transplanting fecal microbiota.}, journal = {Endoscopy international open}, volume = {4}, number = {6}, pages = {E610-3}, pmid = {27556065}, issn = {2364-3722}, abstract = {BACKGROUND AND STUDY AIMS: Placement of a tube through the anus into the cecum has not yet been established as a method of administering whole-colonic treatment. The aim of this study was to evaluate the safety, feasibility, and value of transendoscopic enteral tubing (TET) for fecal microbiota transplantation (FMT) through the colon.<br><br>PATIENTS AND METHODS: A prospective observational study was performed of FMT using a new colonic TET technique. Under endoscopic guidance, a TET tube was affixed to the cecum with clips. The safety, value, and satisfaction with the FMT by TET were evaluated.<br><br>RESULTS: A total of 54 patients underwent TET. The success rate of the TET procedure was 100&#x200a;% (54/54). Duration of the TET procedures was 14.8&#x200a;&#xb1;&#x200a;5.8&#x200a;min. During the TET tube retention period, 98.1&#x200a;% (53/54) of patients were satisfied with TET. The retention time for whole-colon delivery of the fecal microbiota suspension was 12.4&#x200a;&#xb1;&#x200a;2.3 days. In 88.4&#x200a;% (49/54) of cases, no discomfort was reported during injection through the TET tube of the microbiota suspension. No adverse events were see in patients who required tube extubation after FMT.<br><br>CONCLUSIONS: Colonic TET is a novel, safe, convenient, and reliable procedure for FMT that results in a high degree of patient satisfaction.}, }
@article {pmid27548724, year = {2016}, author = {Kump, P and Högenauer, C}, title = {Any Future for Fecal Microbiota Transplantation as Treatment Strategy for Inflammatory Bowel Diseases?.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {34 Suppl 1}, number = {}, pages = {74-81}, doi = {10.1159/000447379}, pmid = {27548724}, issn = {1421-9875}, mesh = {Clostridium Infections/microbiology/therapy ; Colitis, Ulcerative/microbiology/therapy ; Crohn Disease/microbiology/therapy ; Donor Selection ; Fecal Microbiota Transplantation/*trends ; Feces/microbiology ; Female ; *Forecasting ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Male ; Patient Selection ; Pouchitis/microbiology/therapy ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a novel therapeutic procedure aiming at restoring a normal intestinal microbiota by application of fecal microorganisms from a healthy subject into the gastrointestinal tract of a patient. FMT is the most effective treatment for recurrent Clostridium difficile infections (CDI). These infections also occur in patients with inflammatory bowel diseases (IBDs), where case series demonstrated a successful treatment of CDI by FMT in 83-92% of patients. The effect of FMT on the activity of IBD has mainly been investigated in ulcerative colitis (UC) patients, including 3 randomized controlled trials. So far, 2 randomized controlled trials showed a superiority of FMT compared to placebo in inducing remission in UC, while 1 study found no significant difference to placebo. The variation in response to FMT between these studies as well as in the uncontrolled trials might be explained by many differences in the way of FMT application, patient pretreatment and patient and donor selection. The data for the use of FMT in Crohn's disease and pouchitis are sparse; currently, no conclusion can be drawn regarding the effectiveness of FMT in these indications. It needs to be noted that cases of IBD activation after FMT have been reported. So far, FMT can only be recommended to be used for the treatment of concomitant CDI in IBD in clinical practice. For treating IBD irrespective of CDI, FMT should be only used in clinical trials. Current forms of FMT, especially protocols using repeated application, are very time and personnel consuming. Future trends are the use of defined stable microbiota preparations, in particular oral preparations, which will enable better and larger controlled trails for investigating FMT in IBD.}, }
@article {pmid27547010, year = {2016}, author = {Sung, H and Kim, SW and Hong, M and Suk, KT}, title = {Microbiota-based treatments in alcoholic liver disease.}, journal = {World journal of gastroenterology}, volume = {22}, number = {29}, pages = {6673-6682}, pmid = {27547010}, issn = {2219-2840}, mesh = {Animals ; Dysbiosis/etiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Liver Diseases, Alcoholic/immunology/microbiology/*therapy ; Probiotics/therapeutic use ; Toll-Like Receptor 4/physiology ; }, abstract = {Gut microbiota plays a key role in the pathogenesis of alcoholic liver disease (ALD). Consumption of alcohol leads to increased gut permeability, small intestinal bacterial overgrowth, and enteric dysbiosis. These factors contribute to the increased translocation of microbial products to the liver via the portal tract. Subsequently, bacterial endotoxins such as lipopolysaccharide, in association with the Toll-like receptor 4 signaling pathway, induce a gamut of damaging immune responses in the hepatic milieu. Because of the close association between deleterious inflammation and ALD-induced microbiota imbalance, therapeutic approaches that seek to reestablish gut homeostasis should be considered in the treatment of alcoholic patients. To this end, a number of preliminary studies on probiotics have confirmed their effectiveness in suppressing proinflammatory cytokines and improving liver function in the context of ALD. In addition, there have been few studies linking the administration of prebiotics and antibiotics with reduction of alcohol-induced liver damage. Because these preliminary results are promising, large-scale randomized studies are warranted to elucidate the impact of these microbiota-based treatments on the gut flora and associated immune responses, in addition to exploring questions about optimal delivery. Finally, fecal microbiota transplant has been shown to be an effective method of modulating gut microbiota and deserve further investigation as a potential therapeutic option for ALD.}, }
@article {pmid27542133, year = {2016}, author = {Vaughn, BP and Vatanen, T and Allegretti, JR and Bai, A and Xavier, RJ and Korzenik, J and Gevers, D and Ting, A and Robson, SC and Moss, AC}, title = {Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease.}, journal = {Inflammatory bowel diseases}, volume = {22}, number = {9}, pages = {2182-2190}, pmid = {27542133}, issn = {1536-4844}, support = {K23 DK084338/DK/NIDDK NIH HHS/United States ; R03 DK105161/DK/NIDDK NIH HHS/United States ; T32 DK007760/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Crohn Disease/*microbiology/*therapy ; Donor Selection ; Dysbiosis/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/immunology ; Intestines/microbiology ; Male ; Metabolic Networks and Pathways ; Middle Aged ; Prospective Studies ; Remission Induction ; T-Lymphocytes/classification ; United States ; Whole Genome Sequencing ; Young Adult ; }, abstract = {BACKGROUND: The microbiota in the lumen of patients with Crohn's disease (CD) is characterized by reduced diversity, particularly Firmicutes and Bacteroidetes. It is unknown whether the introduction of the intestinal microbiota from healthy individuals could correct this dysbiosis and reverse mucosal inflammation. We investigated the response to fecal microbial transplantation (FMT) from healthy individuals to subjects with active CD.<br><br>METHODS: We performed a prospective open-label study (uncontrolled) of FMT from healthy donors to subjects with active CD. A single FMT was performed by colonoscopy. Recipients' microbial diversity, mucosal T-cell phenotypes, and clinical and inflammatory parameters were measured over 12 weeks, and safety over 26 weeks.<br><br>RESULTS: Nineteen subjects were treated with FMT and completed the study follow-up. Fifty-eight percent (11/19) demonstrated a clinical response (Harvey-Bradshaw Index decrease >3) following FMT. Fifteen subjects had sufficient pre/postfecal samples for analysis. A significant increase in microbial diversity occurred after FMT (P = 0.02). This was greater in clinical responders than nonresponders. Patients who experienced a clinical response demonstrated a significant shift in fecal microbial composition toward their donor's profile as assessed by the Bray-Curtis index at 4 weeks (P = 0.003). An increase in regulatory T cells (CD4CD25CD127lo) was also noted in recipients' lamina propria following FMT. No serious adverse events were noted over the 26-week study period.<br><br>CONCLUSIONS: In this open-label study, FMT led to an expansion in microbial bacterial diversity in patients with active CD. FMT was overall safe, although the clinical response was variable. Determining donor microbial factors that influence clinical response is needed before randomized clinical trials of FMT in CD.}, }
@article {pmid27540307, year = {2016}, author = {Campbell, JP and Vaughn, BP}, title = {Optimal delivery of follow-up care after surgery for Crohn's disease: current perspectives.}, journal = {Clinical and experimental gastroenterology}, volume = {9}, number = {}, pages = {237-248}, pmid = {27540307}, issn = {1178-7023}, support = {UL1 TR000114/TR/NCATS NIH HHS/United States ; }, abstract = {Despite improvements in medical therapies for Crohn's disease (CD), up to 70% of patients require surgery within 10 years of diagnosis. Surgery is not curative, and almost all patients will experience endoscopic recurrence, and many will go on to clinical recurrence. Identifying patients at high-risk of endoscopic recurrence and standardizing postoperative assessments are essential in preventing clinical recurrence of CD. In this review, we discuss the assessment, monitoring, and treatment of postoperative CD patients. We address the various individual risk factors as well as composite risk factors. Medications used for primary CD treatment can be used in the postoperative setting to prevent endoscopic or clinical recurrence with varying efficacy, although the cost-effectiveness of these approaches are not fully understood. Future directions for postoperative CD management include evaluation of newer biologic agents such as anti-integrin therapy and fecal microbiota transplant for prevention of recurrence. Development of a standard preoperative risk assessment tool to clearly stratify those at high-risk of recurrence is necessary to guide empiric therapy. Lastly, the incorporation of noninvasive testing into disease monitoring will likely lead to early detection of endoscopic recurrence that will allow for tailored treatment to prevent clinical recurrence.}, }
@article {pmid27536153, year = {2016}, author = {Hussack, G and Tanha, J}, title = {An update on antibody-based immunotherapies for Clostridium difficile infection.}, journal = {Clinical and experimental gastroenterology}, volume = {9}, number = {}, pages = {209-224}, pmid = {27536153}, issn = {1178-7023}, abstract = {Clostridium difficile continues to be one of the most prevalent hospital-acquired bacterial infections in the developed world, despite the recent introduction of a novel and effective antibiotic agent (fidaxomicin). Alternative approaches under investigation to combat the anaerobic Gram-positive bacteria include fecal transplantation therapy, vaccines, and antibody-based immunotherapies. In this review, we catalog the recent advances in antibody-based approaches under development and in the clinic for the treatment of C. difficile infection. By and large, inhibitory antibodies that recognize the primary C. difficile virulence factors, toxin A and toxin B, are the most popular passive immunotherapies under investigation. We provide a detailed summary of the toxin epitopes recognized by various antitoxin antibodies and discuss general trends on toxin inhibition efficacy. In addition, antibodies to other C. difficile targets, such as surface-layer proteins, binary toxin, motility factors, and adherence and colonization factors, are introduced in this review.}, }
@article {pmid27529553, year = {2016}, author = {Wang, S and Xu, M and Wang, W and Cao, X and Piao, M and Khan, S and Yan, F and Cao, H and Wang, B}, title = {Systematic Review: Adverse Events of Fecal Microbiota Transplantation.}, journal = {PloS one}, volume = {11}, number = {8}, pages = {e0161174}, pmid = {27529553}, issn = {1932-6203}, mesh = {Fecal Microbiota Transplantation/*adverse effects ; Humans ; Safety ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a microbiota-based therapy that shows therapeutic potential in recurrent or refractory Clostridium difficile infections and other intestinal or extra-intestinal disorders. Nonetheless, adverse events (AEs) remain a major challenge in the application of FMT.<br><br>AIM: To review the AEs of FMT and to address the concerns of safety during the procedure.<br><br>METHODS: Publications were retrieved in the databases of Medline, Embase and Cochrane Library. AEs were classified according to their causality with FMT or their severity.<br><br>RESULTS: A total of 7562 original articles about FMT were identified in this study, 50 of them fulfilled the inclusion criteria. Totally 78 kinds of AEs were revealed enrolled in these 50 selected publications. The total incidence rate of AEs was 28.5%. Among the 42 publications, 5 kinds were definitely and 38 kinds were probably related to FMT. The commonest FMT-attributable AE was abdominal discomfort, which was reported in 19 publications. For upper gastrointestinal routes of FMT, 43.6% (89/204) patients were compromised by FMT-attributable AE, while the incidence dropped to 17.7% (76/430) for lower gastrointestinal routes. In contrast, the incidences of serious adverse events (SAEs) were 2.0% (4/196) and 6.1% (40/659) for upper and lower gastrointestinal routes, respectively. A total of 44 kinds of SAEs occurred in 9.2% patients, including death (3.5%, 38/1089), infection (2.5%, 27/1089), relapse of inflammatory bowel diseases (0.6%, 7/1089) and Clostridium difficile infection (0.9%, 10/1089).<br><br>CONCLUSION: Consequently, both AEs and SAEs are not rare and should be carefully monitored throughout FMT. However, high quality randomized controlled trials are still needed for the more definite incidence of AEs of FMT.}, }
@article {pmid27527747, year = {2016}, author = {Jørgensen, SF and Reims, HM and Frydenlund, D and Holm, K and Paulsen, V and Michelsen, AE and Jørgensen, KK and Osnes, LT and Bratlie, J and Eide, TJ and Dahl, CP and Holter, E and Tronstad, RR and Hanevik, K and Brattbakk, HR and Kaveh, F and Fiskerstrand, T and Kran, AB and Ueland, T and Karlsen, TH and Aukrust, P and Lundin, KE and Fevang, B}, title = {A Cross-Sectional Study of the Prevalence of Gastrointestinal Symptoms and Pathology in Patients With Common Variable Immunodeficiency.}, journal = {The American journal of gastroenterology}, volume = {111}, number = {10}, pages = {1467-1475}, pmid = {27527747}, issn = {1572-0241}, mesh = {Abdominal Pain/epidemiology/immunology/pathology ; Adult ; Aged ; Aged, 80 and over ; B-Lymphocytes/immunology ; Celiac Disease/epidemiology/genetics/immunology/pathology ; Colonoscopy ; Common Variable Immunodeficiency/*epidemiology/immunology ; Constipation/epidemiology/immunology/pathology ; Cross-Sectional Studies ; Diarrhea/epidemiology/immunology/pathology ; Duodenum/pathology ; Endoscopy, Digestive System ; Esophageal Mucosa/pathology ; Female ; Gastric Mucosa/pathology ; Gastrointestinal Diseases/*epidemiology/genetics/immunology/pathology ; Gastrointestinal Tract/pathology ; Humans ; Intestinal Mucosa/pathology ; Lymphocytes/pathology ; Male ; Middle Aged ; Plasma Cells/pathology ; Prevalence ; Transcriptome ; Young Adult ; }, abstract = {OBJECTIVES: The objective of this study was to study the prevalence of gastrointestinal (GI) symptoms and histopathology in patients with common variable immunodeficiency (CVID) as well as linking the findings to GI infections and markers of systemic immune activation.<br><br>METHODS: In this cross-sectional study, we addressed GI symptoms in 103 patients and GI histopathological findings in 53 patients who underwent upper and lower endoscopic examination. The most frequent histopathological findings were linked to GI symptoms, B-cell phenotype, and markers of systemic immune activation (soluble (s)CD14, sCD25, and sCD163). Microarray analysis compared "celiac-like disease" in CVID to celiac disease. Screening for selected bacterial and viral infections in fecal samples and gut mucosal biopsies was performed.<br><br>RESULTS: The main findings of this study were as follows: most common GI symptoms were bloating (34%), pain (30%), and diarrhea (26%). The most frequent histopathological findings were increased intraepithelial lymphocytes in the descending part of the duodenum, i.e., "celiac-like disease" (46% of patients), decreased numbers of plasma cells in GI tract mucosa (62%), and lymphoid hyperplasia (38%), none of which were associated with GI symptoms. Reduced plasma cells in GI mucosa were associated with B-cell phenotypic characteristics of CVID, and increased serum levels of sCD14 (P=0.025), sCD25 (P=0.01), and sCD163 (P=0.04). Microarray analyses distinguished between CVID patients with "celiac-like disease" and celiac disease. Positive tests for bacterial and viral infections were scarce both in fecal samples and gut mucosal biopsies, including PCR test for norovirus in biopsy specimens (0 positive tests).<br><br>CONCLUSIONS: In conclusion, GI pathology is common in CVID, but does not necessarily cause symptoms. However, reduced plasma cells in GI mucosa were linked to systemic immune activation, "celiac-like disease" in CVID and true celiac disease appear to be different disease entities, as assessed by gene expression, and infections (including norovirus) are rarely a cause of the CVID enteropathy.}, }
@article {pmid27516814, year = {2016}, author = {, }, title = {Fecal Microbiota Therapy for Clostridium difficile Infection: A Health Technology Assessment.}, journal = {Ontario health technology assessment series}, volume = {16}, number = {17}, pages = {1-69}, pmid = {27516814}, issn = {1915-7398}, mesh = {*Clostridioides difficile ; Diarrhea/*therapy ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/*economics ; Feces/*microbiology ; Humans ; *Microbiota ; Ontario ; Quality of Life ; Quality-Adjusted Life Years ; }, abstract = {BACKGROUND: Fecal microbiota therapy is increasingly being used to treat patients with Clostridium difficile infection. This health technology assessment primarily evaluated the effectiveness and cost-effectiveness of fecal microbiota therapy compared with the usual treatment (antibiotic therapy).<br><br>METHODS: We performed a literature search using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database. For the economic review, we applied economic filters to these search results. We also searched the websites of agencies for other health technology assessments. We conducted a meta-analysis to analyze effectiveness. The quality of the body of evidence for each outcome was examined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Using a step-wise, structural methodology, we determined the overall quality to be high, moderate, low, or very low. We used a survey to examine physicians' perception of patients' lived experience, and a modified grounded theory method to analyze information from the survey.<br><br>RESULTS: For the review of clinical effectiveness, 16 of 1,173 citations met the inclusion criteria. A meta-analysis of two randomized controlled trials found that fecal microbiota therapy significantly improved diarrhea associated with recurrent C. difficile infection versus treatment with vancomycin (relative risk 3.24, 95% confidence interval [CI] 1.85-5.68) (GRADE: moderate). While fecal microbiota therapy is not associated with a significant decrease in mortality compared with antibiotic therapy (relative risk 0.69, 95% CI 0.14-3.39) (GRADE: low), it is associated with a significant increase in adverse events (e.g., short-term diarrhea, relative risk 30.76, 95% CI 4.46-212.44; abdominal cramping, relative risk 14.81, 95% CI 2.07-105.97) (GRADE: low). For the value-for-money component, two of 151 economic evaluations met the inclusion criteria. One reported that fecal microbiota therapy was dominant (more effective and less expensive) compared with vancomycin; the other reported an incremental cost-effectiveness ratio of $17,016 USD per quality-adjusted life-year for fecal microbiota therapy compared with vancomycin. This ratio for the second study indicated that there would be additional cost associated with each recurrent C. difficile infection resolved. In Ontario, if fecal microbiota therapy were adopted to treat recurrent C. difficile infection, considering it from the perspective of the Ministry of Health and Long-Term Care as the payer, an estimated $1.5 million would be saved after the first year of adoption and $2.9 million after 3 years. The contradiction between the second economic evaluation and the savings we estimated may be a result of the lower cost of fecal microbiota therapy and hospitalization in Ontario compared with the cost of therapy used in the US model. Physicians reported that C. difficile infection significantly reduced patients' quality of life. Physicians saw fecal microbiota therapy as improving patients' quality of life because patients could resume daily activities. Physicians reported that their patients were happy with the procedures required to receive fecal microbiota therapy.<br><br>CONCLUSIONS: In patients with recurrent C. difficile infection, fecal microbiota therapy improves outcomes that are important to patients and provides good value for money.}, }
@article {pmid27513403, year = {2016}, author = {Çetinkaya, &#xdc; and Yazar, S and Kuk, S and Sivcan, E and Kaynar, L and Arslan, D and Şahin, &#x130;}, title = {The high prevalence of Encephalitozoon intestinalis in patients receiving chemotherapy and children with growth retardation and the validity of real-time PCR in its diagnosis.}, journal = {Turkish journal of medical sciences}, volume = {46}, number = {4}, pages = {1050-1058}, doi = {10.3906/sag-1504-69}, pmid = {27513403}, issn = {1300-0144}, mesh = {Child ; Encephalitozoon ; Encephalitozoonosis/*epidemiology ; Feces ; Humans ; Prevalence ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; }, abstract = {BACKGROUND/AIM: The aim of this study was to investigate the presence of Encephalitozoon intestinalis in different patient groups consisting of immunocompromised and immunocompetent individuals.<br><br>MATERIALS AND METHODS: The stool samples of 100 patients consisting of 25 patients receiving chemotherapy and with acute gastrointestinal complaints, 25 with bone marrow transplant and acute gastrointestinal complaints, 25 with urticaria, and 25 with growth retardation were included in the study. As control groups, 25 subjects without any chronic disease but with acute gastrointestinal complaints and 25 healthy volunteers, making a total of 50 subjects, were included in the study. E. intestinalis was investigated by IFA-MAbs and molecular methods.<br><br>RESULTS: Forty percent of patients receiving chemotherapy and with acute gastrointestinal complaints, 24% of patients with bone marrow transplant and acute gastrointestinal complaints, 20% of patients with urticaria, 40% of children with growth retardation, and 28% of patients without any chronic disease but with acute gastrointestinal complaints were determined as positive.<br><br>CONCLUSION: To the best of our knowledge, this is the first report to assess the relationship between E. intestinalis and growth retardation. We think that the reliability of the use of molecular methods, especially real-time PCR, should be improved for the diagnosis of E. intestinalis.}, }
@article {pmid27513211, year = {2017}, author = {Khoruts, A and Hippen, KL and Lemire, AM and Holtan, SG and Knights, D and Young, JH}, title = {Toward revision of antimicrobial therapies in hematopoietic stem cell transplantation: target the pathogens, but protect the indigenous microbiota.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {179}, number = {}, pages = {116-125}, pmid = {27513211}, issn = {1878-1810}, support = {UL1 TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Anti-Infective Agents/*pharmacology ; Dysbiosis/immunology/microbiology/therapy ; Gastrointestinal Tract/drug effects/microbiology/pathology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Microbiota/*drug effects ; }, abstract = {Host microbiota plays important roles in providing colonization resistance to pathogens and instructing development and function of the immune system. Antibiotic treatments intended to target pathogens further weaken the host defenses and may paradoxically increase the risk of systemic infections. This consequence is especially problematic in patients undergoing hematopoietic stem cell transplantation, where the mucosal defenses are already weakened by the conditioning regimens. This review discusses the roles that indigenous microbiota plays in protecting the host and maintaining immune homeostasis. In addition, we highlight possible strategies that are being developed to allow targeted antimicrobial therapy against pathogens, while minimizing the harm to indigenous microbiota.}, }
@article {pmid27509341, year = {2016}, author = {von Müller, L}, title = {[New aspects on Clostridium difficile infection].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {141}, number = {16}, pages = {1144-1147}, doi = {10.1055/s-0042-107443}, pmid = {27509341}, issn = {1439-4413}, mesh = {Anti-Bacterial Agents ; *Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; Molecular Epidemiology ; }, abstract = {Clostridium difficile infection (CDI) is a frequent and complex disease which is influenced by the repertoire of bacterial virulence factors, by host immunity and by the intestinal microbiome. These complex interaction opens a number of options which may be used for treatment in the future. One example for new treatment options is fecal microbiota transplantation (FMT). Driven by C. difficile related research activities the knowledge of protective microorganism is increasing and it may be assumed that bacteriotherapy by next-generation probiotics may be used very soon also for other diseases. Very often, CDI reflects to the clinician that antibiotic therapy is associated with side effects. Therefore, C. difficile is the guilty conscience which helps to implement targeted and restrictive antibiotic use in the daily practice.}, }
@article {pmid27507347, year = {2016}, author = {Perez, E and Lee, CH and Petrof, EO}, title = {A Practical Method for Preparation of Fecal Microbiota Transplantation.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1476}, number = {}, pages = {259-267}, doi = {10.1007/978-1-4939-6361-4_19}, pmid = {27507347}, issn = {1940-6029}, mesh = {Clostridioides difficile/*pathogenicity/physiology ; Colon/microbiology/pathology ; Enterocolitis, Pseudomembranous/microbiology/pathology/*therapy ; Fecal Microbiota Transplantation/instrumentation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Humans ; Patient Selection/ethics ; Tissue Donors/ethics ; }, abstract = {Clostridium difficile is a challenging infection that can be difficult to treat with antibiotic therapy. This chapter outlines the processing material for fecal microbiota transplantation (FMT), also known as stool transplant. Fecal transplantations are effective in treating recurrent C. difficile infection (CDI). FMT uses a stool sample collected from a healthy, screened donor to restore healthy microbiota in the colon of a patient with CDI for symptom resolution. Here, we describe a rapid method for FMT preparation that uses inexpensive and disposable materials.}, }
@article {pmid27504814, year = {2016}, author = {Wadhwani, SI and Nakayuenyongsuk, W and Shinn, L and Chase, P and Kharbanda, S and Bass, D and Park, KT}, title = {Predictive Value of Fecal Calprotectin in Pediatric Graft-Versus-Host Disease.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {63}, number = {6}, pages = {e208-e209}, doi = {10.1097/MPG.0000000000001369}, pmid = {27504814}, issn = {1536-4801}, mesh = {Feces/*chemistry ; Graft vs Host Disease/*diagnosis ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Intestinal Diseases/diagnosis/immunology ; Leukocyte L1 Antigen Complex/*analysis ; Risk Factors ; }, }
@article {pmid27502733, year = {2016}, author = {von Moos, S and Cippà, PE and Wüthrich, RP and Mueller, TF}, title = {Intestinal infection at onset of mycophenolic acid-associated chronic diarrhea in kidney transplant recipients.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {18}, number = {5}, pages = {721-729}, doi = {10.1111/tid.12590}, pmid = {27502733}, issn = {1399-3062}, mesh = {Adult ; Area Under Curve ; Chronic Disease ; Colitis/epidemiology/etiology/*physiopathology ; Colon/*microbiology/pathology ; Diarrhea/epidemiology/*etiology/*physiopathology ; Feces/microbiology ; Female ; Follow-Up Studies ; Humans ; Immunosuppressive Agents/administration &amp; dosage/*adverse effects ; Incidence ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Mycophenolic Acid/administration &amp; dosage/*adverse effects/therapeutic use ; Retrospective Studies ; Switzerland/epidemiology ; Transplant Recipients ; Transplantation, Homologous/adverse effects ; Weight Loss ; }, abstract = {BACKGROUND: Chronic diarrhea after kidney transplantation is often attributed to mycophenolic acid (MPA) toxicity. We hypothesize that intestinal infections contribute to the pathogenesis of chronic MPA-associated diarrhea.<br><br>METHODS: In this retrospective study, all patients (n = 726) receiving a kidney transplant between 2000 and 2010 at the University Hospital Zurich were followed until July 2014 for occurrence of chronic diarrhea (&#x2265;4 weeks). Infectious triggers at diarrhea onset were assessed by reviewing medical history, stool microbiology, and histology of colon biopsies.<br><br>RESULTS: In 46 patients (6.3% of the cohort), a total of 51 episodes of chronic diarrhea during MPA treatment were documented. The diarrhea episodes were often severe, as confirmed by significant weight loss. The cumulative incidence of chronic diarrhea was uniformly distributed throughout the post-transplant period, with 2.0%, 5.1%, and 9.6% at 1, 5, and 10 years, respectively. Evidence was found for intestinal infection at diarrhea onset in 38 episodes (74.5%). Occurrence of diarrhea onset showed a seasonal distribution with peaks in April and October/November. Specific antimicrobial treatment alone was associated with a 19% resolution rate only, whereas combination with dose reduction of MPA or switch from mycophenolate mofetil to enteric-coated mycophenolate sodium resulted in a 22.7% and 76.5% resolution rate, respectively. Change to an MPA-free regimen was associated with a 100% resolution rate.<br><br>CONCLUSION: These results provide first evidence for a contribution of intestinal infections in chronic post-transplant diarrhea associated with MPA treatment.}, }
@article {pmid27496525, year = {2016}, author = {Loke, P and Heine, RG and McWilliam, V and Cameron, DJ and Tang, ML and Allen, KJ}, title = {Fecal microbial transplantation in a pediatric case of recurrent Clostridium difficile infection and specific antibody deficiency.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {27}, number = {8}, pages = {872-874}, doi = {10.1111/pai.12619}, pmid = {27496525}, issn = {1399-3038}, mesh = {Child ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Infant ; Male ; Recurrence ; }, }
@article {pmid27496472, year = {2016}, author = {Grąt, M and Wronka, KM and Krasnodębski, M and Masior, &#x141; and Lewandowski, Z and Kosińska, I and Grąt, K and Stypułkowski, J and Rejowski, S and Wasilewicz, M and Gałęcka, M and Szachta, P and Krawczyk, M}, title = {Profile of Gut Microbiota Associated With the Presence of Hepatocellular Cancer in Patients With Liver Cirrhosis.}, journal = {Transplantation proceedings}, volume = {48}, number = {5}, pages = {1687-1691}, doi = {10.1016/j.transproceed.2016.01.077}, pmid = {27496472}, issn = {1873-2623}, mesh = {Adult ; Aged ; Disease Progression ; Escherichia coli ; Female ; *Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis/*complications/*microbiology ; Liver Neoplasms/*microbiology ; Liver Transplantation ; Male ; Middle Aged ; }, abstract = {BACKGROUND: Changes within the gut microbiota contribute to the progression of chronic liver diseases. According to the results of several studies performed in animal models, gut dysbiosis plays an important role in hepatocarcinogenesis. The aim of this study was to explore the characteristics of gut microbiota associated with the presence of hepatocellular cancer (HCC) in patients with cirrhosis of the liver undergoing liver transplantation.<br><br>METHODS: A total of 15 patients with HCC and 15 non-HCC patients matched according to etiology of cirrhosis and Model for End-Stage Liver Disease (MELD) scores who underwent liver transplantations between 2012 and 2014 were included. Analysis of their gut microbial profile was based on prospectively collected stool samples from the pretransplant period.<br><br>RESULTS: Patients with and without HCC were similar with respect to age (P&#xa0;= .506), sex (P&#xa0;= .700), hepatitis C virus (P&#xa0;> .999) and hepatitis B virus (P&#xa0;= .715) infection status, alcoholic liver disease (P&#xa0;> .999), and MELD score (P&#xa0;= .337). Notably, the presence of HCC was associated with significantly increased fecal counts of Escherichia coli (P&#xa0;= .025). Prediction of HCC presence based on E coli counts was associated with the area under the receiver-operating curve of 0.742 (95% confidence interval, 0.564-0.920), with the optimal cutoff on the level of 17.728 (natural logarithm of colony-forming units per 1&#xa0;g of feces). Sensitivity and specificity rates for the established cutoff were 66.7% and 73.3%, respectively.<br><br>CONCLUSIONS: The profile of gut microbiota associated with the presence of HCC in cirrhotic patients is characterized by increased fecal counts of E coli. Therefore, intestinal overgrowth of E coli may contribute to the process of hepatocarcinogenesis.}, }
@article {pmid27496448, year = {2016}, author = {Dobies, A and Renke, M and Wołyniec, W and Palenicek, L and Januszczyk, J and Król, E and Lizakowski, S and Rutkowski, P and Tylicki, L and Dębska-Ślizień, A and Rutkowski, B}, title = {Gastrointestinal Pathologies in Patients After Successful Renal Transplantation-A Pilot Study.}, journal = {Transplantation proceedings}, volume = {48}, number = {5}, pages = {1566-1569}, doi = {10.1016/j.transproceed.2016.02.060}, pmid = {27496448}, issn = {1873-2623}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Gastrointestinal Neoplasms/*epidemiology ; Humans ; Kidney Transplantation/*adverse effects/statistics &amp; numerical data ; Male ; Middle Aged ; Pilot Projects ; Prevalence ; Young Adult ; }, abstract = {BACKGROUND: The beneficial effect of kidney transplantation in patients requiring continuous renal replacement therapy owing to chronic kidney disease is well known and accepted. Kidney transplantation protects the patient from complications that may develop during chronic dialysis. Unfortunately, there is also evidence that kidney transplant patients are more prone to developing cancer than healthy persons. The aim of this study was to evaluate the prevalence of gastrointestinal pathologies in patients after kidney transplantation.<br><br>METHODS: Adult patients after kidney transplantation, who are under the care of the Outpatient Department of Nephrology in Gda&#x144;sk, received alarm symptom questionnaires and referral for testing for the presence of fecal occult blood. Then, in 45 selected patients (29 men and 16 women) endoscopic examination was performed. Mean age was 57.6 &#xb1; 10.1 (range, 35-83) years.<br><br>RESULTS: Out of &#x223c;940 patients after kidney transplantation, resting under supervision of outpatient department, 181 patients completed the questionnaire and 100 gave a stool sample for testing: 32 results were positive. After analyzing the questionnaires and stool results, 88 patients were qualified for further investigation. The endoscopic examination had been performed so far in 45 patients and revealed gastritis and/or duodenitis in 33 patients, diverticular colon disease in 18, esophagitis in 8, colon polyps in 14, stomach polyps in 3, inflammatory bowel disease in 7, and cancers in&#xa0;3.<br><br>CONCLUSIONS: The preliminary results indicate that patients after kidney transplantation have significant risk of gastrointestinal pathologies and require detailed diagnostic endoscopy.}, }
@article {pmid27493597, year = {2016}, author = {Lopez, J and Grinspan, A}, title = {Fecal Microbiota Transplantation for Inflammatory Bowel Disease.}, journal = {Gastroenterology &amp; hepatology}, volume = {12}, number = {6}, pages = {374-379}, pmid = {27493597}, issn = {1554-7914}, abstract = {The gut bacterial microbiome, particularly its role in disease and inflammation, has gained international attention with the successful use of fecal microbiota transplantation (FMT) in the treatment of Clostridium difficile infection. This success has led to studies exploring the role of FMT in other conditions, including inflammatory bowel disease (IBD). Both Crohn's disease and ulcerative colitis are chronic inflammatory conditions of the gastrointestinal system that have multifactorial etiologies. A shift in gut microbial composition in genetically susceptible individuals, an altered immune system, and environmental factors are all hypothesized to have a role in the pathogenesis of IBD. While numerous case reports and cohort studies have described the use of FMT in patients with IBD over the last 2 decades, the development of new sequencing techniques and results from 2 recent randomized, controlled trials have allowed for a better understanding of the relationship between the microbiome and the human host. However, despite these efforts, knowledge remains limited and the role of FMT in the management of IBD remains uncertain. Further investigation is necessary before FMT joins the current armamentarium of treatment options in clinical practice.}, }
@article {pmid27492796, year = {2016}, author = {Ciricillo, J and Haslam, D and Blum, S and Kim, MO and Liu, C and Paulsen, G and Courter, J and Danziger-Isakov, L}, title = {Frequency and risks associated with Clostridium difficile-associated diarrhea after pediatric solid organ transplantation: a single-center retrospective review.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {18}, number = {5}, pages = {706-713}, doi = {10.1111/tid.12584}, pmid = {27492796}, issn = {1399-3062}, mesh = {Adolescent ; Anti-Bacterial Agents/adverse effects/therapeutic use ; Child ; Child, Preschool ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*epidemiology/microbiology ; Diarrhea/*epidemiology/microbiology ; Feces/*microbiology ; Female ; Hospitalization ; Humans ; Immunosuppression Therapy/adverse effects ; Infant ; Infant, Newborn ; Male ; Odds Ratio ; Organ Transplantation/*adverse effects ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Morbidity and mortality related to Clostridium difficile infection (CDI) has increased, but epidemiology and risk factors within pediatric solid organ transplant (SOT) recipients are uncertain.<br><br>METHODS: A retrospective cohort study of SOT recipients age &#x2264;18 years at transplantation from 2010 to 2013 was performed. Patients with CDI were compared with matched CDI-negative controls with diarrhea.<br><br>RESULTS: Of 202 patients, the majority were male (58%) and Caucasian (77%). Kidney (42%) was the most common organ transplanted, followed by liver (38%), heart (17%), and multivisceral/intestine (3%). Age ranged from 3 weeks to 18 years (median 4.7 years, mean 6.6; interquartile range [IQR] 1.5-11.2). In 104 SOT recipients, at least 1 unformed stool was tested; 25 patients were positive for CDI. Most testing occurred by 60 days post transplant (mean 164, median 57, IQR 14-227). First negative tests occurred concurrently (mean 153, median 54, IQR 13-214) to the 25 patients with CDI (mean 199, median 65, IQR 32-238). In univariable analyses, age, gender, ethnicity, obesity, and calcineurin inhibitor choice were not associated with CDI. Liver recipients were more likely to have CDI (18.4% liver, 4.7% kidney, 8.8% heart, P < 0.01). Twenty CDI patients were matched to 35 controls. In multivariable analyses, neither recent hospitalization nor antibiotic duration or intensity was associated with CDI. Acid-blockade appeared protective (risk ratio 0.13, 95% confidence interval 0.02-0.78).<br><br>CONCLUSIONS: CDI occurs in 12% of pediatric SOT recipients, but 24% of those tested with diarrhea were positive. In patients with diarrhea, prior hospitalization and antibiotic duration or intensity were not associated with CDI.}, }
@article {pmid27491067, year = {2016}, author = {Kelly, JR and Borre, Y and O' Brien, C and Patterson, E and El Aidy, S and Deane, J and Kennedy, PJ and Beers, S and Scott, K and Moloney, G and Hoban, AE and Scott, L and Fitzgerald, P and Ross, P and Stanton, C and Clarke, G and Cryan, JF and Dinan, TG}, title = {Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat.}, journal = {Journal of psychiatric research}, volume = {82}, number = {}, pages = {109-118}, doi = {10.1016/j.jpsychires.2016.07.019}, pmid = {27491067}, issn = {1879-1379}, mesh = {Adult ; Aged ; Animals ; C-Reactive Protein/metabolism ; Case-Control Studies ; Corticosterone/blood ; Cytokines/blood ; Depression/*microbiology/*pathology ; Disease Models, Animal ; Feces/microbiology ; Female ; Food Preferences/physiology ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Hydrocortisone/metabolism ; Kynurenine/blood ; Lipopolysaccharides/blood/pharmacology ; Male ; Maze Learning/physiology ; Middle Aged ; RNA, Ribosomal, 16S/metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gut microbiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.}, }
@article {pmid27489376, year = {2016}, author = {Evrensel, A and Ceylan, ME}, title = {Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders.}, journal = {Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology}, volume = {14}, number = {3}, pages = {231-237}, pmid = {27489376}, issn = {1738-1088}, abstract = {Fecal microbiota transplantation has a 1700-year history. This forgotten treatment method has been put into use again during the last 50 years. The interest in microbiota-gut-brain axis and fecal microbiota transplantation is rapidly increasing. New evidence is obtained in the etiopathogenesis of neuropsychiatric disorders. There is a large number of experimental and clinical researches in the field of gut-brain axis. There is limited information on fecal microbiota transplantation. Despite this, initial results are promising. It is commonly used in the treatment of gastrointestinal diseases such as Clostridium difficile infection, Crohn's disease, ulcerative colitis. It is also experimentally used in the treatment of metabolic and autoimmune diseases. There are case reports that it is effective in the treatment of autism, Parkinson's disease, multiple sclerosis, chronic fatigue syndrome and irritable bowel syndrome. Its implementation is easy, and it is a cheap and reliable treatment method. However, the long-term risks are unknown. Additionally, standard application protocols have not yet been established. There are a lot of questions to be answered. A university in Turkey has got official permission this year, and started to apply fecal microbiota transplantation. In this review, neuropsychiatric areas of use of fecal microbiota transplantation have been discussed in the light of the current information.}, }
@article {pmid27488951, year = {2016}, author = {Wang, M and Liang, C and Hu, H and Zhou, L and Xu, B and Wang, X and Han, Y and Nie, Y and Jia, S and Liang, J and Wu, K}, title = {Intraperitoneal injection (IP), Intravenous injection (IV) or anal injection (AI)? Best way for mesenchymal stem cells transplantation for colitis.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {30696}, pmid = {27488951}, issn = {2045-2322}, mesh = {Administration, Rectal ; Animals ; Cell Adhesion Molecules/metabolism ; Cell- and Tissue-Based Therapy/*methods ; Colitis/chemically induced/*therapy ; Colon/pathology ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; Injections, Intraperitoneal ; Injections, Intravenous ; Interleukin-10/metabolism ; Ki-67 Antigen/metabolism ; Lymph Nodes/cytology ; Male ; Mesenchymal Stem Cell Transplantation/*methods ; Mesenchymal Stem Cells ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Occult Blood ; Treatment Outcome ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Stem cell transplantation showed promising results in IBD management. However, the therapeutic impacts of cell delivery route that is critical for clinical translation are currently poorly understood. Here, three different MSCs delivery routes: intraperitoneal (IP), intravenous (IV), and anal injection (AI) were compared on DSS-induced colitic mice model. The overall therapeutic factors, MSCs migration and targeting as well as local immunomodulatory cytokines and FoxP3(+) cells infiltration were analyzed. Colitis showed varying degrees of alleviation after three ways of MSCs transplantation, and the IP injection showed the highest survival rate of 87.5% and displayed the less weight loss and quick weight gain. The fecal occult blood test on the day 3 also showed nearly complete absence of occult blood in IP group. The fluorescence imaging disclosed higher intensity of engrafted cells in inflamed colon and the corresponding mesentery lymph nodes (MLNs) in IP and AI groups than the IV group. Real time-PCR and ELISA also demonstrate lower TNF-α and higher IL-10, TSG-6 levels in IP group. The immunohistochemistry indicated higher repair proliferation (Ki-67) and more FoxP3(+) cells accumulation of IP group. IP showed better colitis recovery and might be the optimum MSCs delivery route for the treatment of DSS-induced colitis.}, }
@article {pmid27488366, year = {2016}, author = {Galvão, FH and Waisberg, DR and Seid, VE and Costa, AC and Chaib, E and Baptista, RR and Capelozzi, VL and Lanchotte, C and Cruz, RJ and Araki, J and D'Albuquerque, LC}, title = {Allogeneic anorectal transplantation in rats: technical considerations and preliminary results.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {30894}, pmid = {27488366}, issn = {2045-2322}, mesh = {Anal Canal/*transplantation ; Anastomosis, Surgical/methods ; Animals ; Aorta/*transplantation ; Colostomy/adverse effects ; Male ; Mesenteric Artery, Inferior/*transplantation ; Portal Vein/*transplantation ; Quality of Life ; Rats ; Rats, Inbred Lew ; Rats, Wistar ; Plastic Surgery Procedures/*methods ; Transplantation, Homologous ; }, abstract = {Fecal incontinence is a challenging condition with numerous available treatment modalities. Success rates vary across these modalities, and permanent colostomy is often indicated when they fail. For these cases, a novel potential therapeutic strategy is anorectal transplantation (ATx). We performed four isogeneic (Lewis-to-Lewis) and seven allogeneic (Wistar-to-Lewis) ATx procedures. The anorectum was retrieved with a vascular pedicle containing the aorta in continuity with the inferior mesenteric artery and portal vein in continuity with the inferior mesenteric vein. In the recipient, the native anorectal segment was removed and the graft was transplanted by end-to-side aorta-aorta and porto-cava anastomoses and end-to-end colorectal anastomosis. Recipients were sacrificed at the experimental endpoint on postoperative day 30. Surviving animals resumed normal body weight gain and clinical performance within 5 days of surgery. Isografts and 42.9% of allografts achieved normal clinical evolution up to the experimental endpoint. In 57.1% of allografts, signs of immunological rejection (abdominal distention, diarrhea, and anal mucosa inflammation) were observed three weeks after transplantation. Histology revealed moderate to severe rejection in allografts and no signs of rejection in isografts. We describe a feasible model of ATx in rats, which may allow further physiological and immunologic studies.}, }
@article {pmid27484187, year = {2016}, author = {Brunet, J and Lemoine, JP and Pesson, B and Valot, S and Sautour, M and Dalle, F and Muller, C and Borni-Duval, C and Caillard, S and Moulin, B and Pfaff, AW and Razakandrainibe, R and Abou-Bacar, A and Favennec, L and Candolfi, E}, title = {Ruling out nosocomial transmission of Cryptosporidium in a renal transplantation unit: case report.}, journal = {BMC infectious diseases}, volume = {16}, number = {}, pages = {363}, pmid = {27484187}, issn = {1471-2334}, mesh = {Acute Kidney Injury/etiology/parasitology ; Adult ; Animals ; Coccidiostats/therapeutic use ; Cross Infection/*parasitology ; Cryptosporidiosis/complications/drug therapy/*transmission ; Cryptosporidium/genetics/*pathogenicity ; Diarrhea/etiology/parasitology ; Feces/parasitology ; Female ; Humans ; Immunocompromised Host ; *Kidney Transplantation ; Male ; Middle Aged ; Nitro Compounds ; Thiazoles/therapeutic use ; }, abstract = {BACKGROUND: Cryptosporidium spp. is a ubiquitous parasite affecting humans as well as domestic and wild vertebrates, causing diarrhea in both immunocompetent and immunocompromised hosts worldwide. Its transmission occurs primarily by the fecal-oral route. In humans, C. parvum and C. hominis are the most prevalent species, whereas immunocompetent and immunocompromised individuals can also be infected by other zoonotic species. Renal transplant patients are prone to develop cryptosporidiosis, which can induce severe and life-threatening diarrhea.<br><br>CASE PRESENTATION: We report here a series of nearly concomitant cases of acute symptomatic cryptosporidiosis in three renal transplant patients attending the Strasbourg University Hospital Nephrology Unit. The clinical presentation was persistent diarrhea and acute renal failure. The diagnosis was confirmed by microscopic stool examination using a modified Ziehl-Neelsen staining method and species identification by molecular tools. All patients were treated with nitazoxanide and recovered from diarrhea after 14&#xa0;days of therapy.<br><br>CONCLUSION: Genotypic species identification was not consistent with an epidemic context, thus underlining the need for genotyping to monitor at risk patients.}, }
@article {pmid27482700, year = {2016}, author = {Evrensel, A and Ceylan, ME}, title = {[The Future of Fecal Microbiota Transplantation Method In Neuropsychiatric Disorders].}, journal = {Turk psikiyatri dergisi = Turkish journal of psychiatry}, volume = {27}, number = {1}, pages = {71-72}, pmid = {27482700}, issn = {2651-3463}, mesh = {*Feces ; Forecasting ; Humans ; Mental Disorders/*therapy ; *Microbiota ; Transplantation ; }, abstract = {Letter to the editor.}, }
@article {pmid27482184, year = {2015}, author = {Rubin, DT}, title = {Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease.}, journal = {Gastroenterology &amp; hepatology}, volume = {11}, number = {9}, pages = {618-620}, pmid = {27482184}, issn = {1554-7914}, }
@article {pmid27474685, year = {2017}, author = {Wolf-Meyer, MJ}, title = {Normal, Regular, and Standard: Scaling the Body through Fecal Microbial Transplants.}, journal = {Medical anthropology quarterly}, volume = {31}, number = {3}, pages = {297-314}, doi = {10.1111/maq.12328}, pmid = {27474685}, issn = {0745-5194}, mesh = {Anthropology, Medical ; *Clostridioides difficile ; *Enterocolitis, Pseudomembranous/ethnology/microbiology/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; United States/ethnology ; }, abstract = {In 2013, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) held a workshop to determine the risks and benefits associated with the experimental use of fecal microbial transplants to treat Clostridium difficile and other gastroenterological disorders. By focusing on the proceedings of the NIH-FDA workshop on the treatment of the human microbiome, the question of how medicine colonizes human bodies through microbial transplants raises questions about what an individual body is, how determinative of human health the microbiome is, and what the limits of molecular biomedicine are when the microbiome is taken into consideration. In the workshop presentations and discussion of this emerging treatment, experts used ideas about the normal, regular, and standard to move between scales of bodily analysis, from the microbial to the body politic, demonstrating how the individual and society are deeply influenced by the unruly community of microbial symbiotes that humans host.}, }
@article {pmid27472679, year = {2016}, author = {Xu, L and Zhang, T and Cui, B and He, Z and Xiang, J and Long, C and Peng, Z and Li, P and Huang, G and Ji, G and Zhang, F}, title = {Clinical efficacy maintains patients' positive attitudes toward fecal microbiota transplantation.}, journal = {Medicine}, volume = {95}, number = {30}, pages = {e4055}, pmid = {27472679}, issn = {1536-5964}, mesh = {Adult ; *Attitude to Health ; China ; Crohn Disease/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; *Patient Satisfaction ; Prospective Studies ; Surveys and Questionnaires ; }, abstract = {Few studies have been conducted on the attitudes of patients seeking fecal microbiota transplantation (FMT). This study aimed to investigate the reasons for patients with Crohn's disease (CD) seeking FMT and their attitude changes after FMT.In this prospective study, all included patients were diagnosed with CD for at least 6 months and intended to receive FMT. A questionnaire was designed to investigate the history of medical visits and patients' attitudes toward FMT. Only refractory patients who failed to clinically respond to previous treatment were selected for undergoing FMT. Three months after the first FMT, patients were required to complete the second questionnaire on attitudes toward the first FMT.A total of 207 patients with CD were included for questionnaire survey. In 118 refractory patients, 94.07% sought FMT because they had no other choice. In 89 nonrefractory patients, 78.65% sought FMT for the reason that they wanted to achieve better clinical results or even a cure, although the current treatment was effective for them. In all, 118 refractory patients received FMT. Three months after the first FMT, 88.98% (105/118) patients completed the questionnaire on patients' attitudes toward FMT. Of these 105 patients, 56.19% reported to have satisfactory clinical efficacy and 74.29% were willing to receive the second FMT. Moreover, 89.52% (94/105) showed their willingness to recommend FMT to other patients.In conclusion, this study at least first time demonstrated that patients with CD were willing to accept FMT due to its efficacy.}, }
@article {pmid27472021, year = {2016}, author = {Souadka, A and Majbar, MA and Amrani, L and Souadka, A}, title = {Perineal pseudocontinent colostomy for ultra-low rectal adenocarcinoma: the muscular graft as a pseudosphincter.}, journal = {Acta chirurgica Belgica}, volume = {116}, number = {5}, pages = {278-281}, doi = {10.1080/00015458.2016.1174020}, pmid = {27472021}, issn = {0001-5458}, mesh = {Adenocarcinoma/pathology/*surgery ; Adult ; Aged ; Anal Canal/physiology ; Cohort Studies ; Colostomy/*methods ; Fecal Incontinence/prevention &amp; control ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Middle Aged ; Myocutaneous Flap/*statistics &amp; numerical data ; Perineum/*surgery ; Quality of Life ; Rectal Neoplasms/pathology/*surgery ; Retrospective Studies ; Risk Assessment ; Tissue Transplantation/methods ; Treatment Outcome ; }, abstract = {BACKGROUND AND STUDY AIM: The aim of this study was to analyze objectively the role of the muscular graft in the continence using manometric study in the patients who underwent pseudocontinent perineal colostomy after abdominoperineal resection for rectal adenocarcinoma.<br><br>PATIENTS AND METHODS: This was a retrospective study including all the patients from January 2002 to December 2009 who underwent an abdominoperineal resection followed by perineal pseudocontinent colostomy for ultra-low rectal adenocarcinoma and agreed to perform the manometric evaluation of the muscular graft.<br><br>RESULTS: Fifteen patients were included, six males and nine females, with a mean age of 50 years. According to Kirwan's classification, 2 (13.3%) patients had normal continence (Stage A) had 10 (66.6%) no soiling (stage B) and 3 (20%) patients had minimal soiling (Stage C). The manometric evaluation was performed after a median period of 12 months post-surgery. The mean maximal resting and squeeze pressures were respectively 41 cmH2O and 59 cmH2O and the mean colonic sensory volume was 12&#x2009;ml.<br><br>CONCLUSION: This study showed that the musculae graft of Pseudocontinent Perineal colostomy acted as a hypotonic sphincter that pressure can increase during the voluntary squeeze. These data may help to clarify the functional outcomes of this technique after APR for ultra-low rectal adenocarcinoma.}, }
@article {pmid27471167, year = {2016}, author = {Brüssow, H}, title = {Biome engineering-2020.}, journal = {Microbial biotechnology}, volume = {9}, number = {5}, pages = {553-563}, pmid = {27471167}, issn = {1751-7915}, mesh = {Bacteriophages ; Dysbiosis/*therapy ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Probiotics ; }, abstract = {The gut microbiome research is going from a descriptive into an intervention phase. To optimize beneficial microbe-host interaction, we need to understand how to steer the system by modulating the nutrient input with which the system is literally fed (e.g. diets, fibres, prebiotics, human milk oligosaccharides), and we must learn how to modulate the composition of the gut microbiota by adding beneficial microbes (e.g. probiotics, faecal transplants) and by eliminating disturbing microbial members using, for example, bacteriophages in this highly complex ecosystem. The current status of the field is reviewed together with an outlook what might be expected until 2020, highlighting obstacles to progress and possible solutions to these problems.}, }
@article {pmid27466067, year = {2016}, author = {Maneu, V and Noailles, A and Gómez-Vicente, V and Carpena, N and Cuenca, N and Gil, ML and Gozalbo, D}, title = {Immunosuppression, peripheral inflammation and invasive infection from endogenous gut microbiota activate retinal microglia in mouse models.}, journal = {Microbiology and immunology}, volume = {60}, number = {9}, pages = {617-625}, doi = {10.1111/1348-0421.12405}, pmid = {27466067}, issn = {1348-0421}, mesh = {Animals ; Biomarkers ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome/immunology ; Immunophenotyping ; Immunosuppression Therapy ; Mice ; Mice, Knockout ; Microglia/*immunology/metabolism ; Retinitis/genetics/*immunology/*microbiology/pathology ; Toll-Like Receptor 2/genetics/metabolism ; }, abstract = {Although its actual role in the progression of degenerative processes is not fully known, the persistent activated state of retinal microglia and the concurrent secretion of inflammatory mediators may contribute to neuronal death and permanent vision loss. Our objective was to determine whether non-ocular conditions (immunosuppression and peripheral inflammation) could lead to activation of retinal microglia. Mouse models of immunosuppression induced by cyclophosphamide and/or peripheral inflammation by chemically induced sublethal colitis in C57BL/6J mice were used. Retinal microglia morphology, spatial distribution and complexity, as well as MHCII and CD11b expression levels were determined by flow cytometry and confocal immunofluorescence analysis with anti-CD11b, anti-IBA1 and anti-MHCIIRT1B antibodies. Retinas of mice with double treatment showed changes in microglial morphology, spatial distribution and expression levels of CD11b and MHCII. These effects were higher than those observed with any treatment separately. In addition, we also observed in these mice: (i) translocation of endogenous bacteria from gut to liver, and (ii) upregulation of TLR2 expression in retinal microglia. Using a mouse model of immunosuppression and gut colonization by Candida albicans, translocation of fungal cells was confirmed to occur in wild type and, to a higher extent, in TLR2 KO mice, which are more susceptible to fungal invasion; interestingly microglial changes were also higher in TLR2 KO mice. Hence, non-ocular injuries (immunosuppression, peripheral inflammation and invasive infection from endogenous gut microbiota) can activate retinal microglia and therefore could affect the progression of neurodegenerative disorders and should be taken into account to improve therapeutic options.}, }
@article {pmid27461930, year = {2016}, author = {Kakihana, K and Fujioka, Y and Suda, W and Najima, Y and Kuwata, G and Sasajima, S and Mimura, I and Morita, H and Sugiyama, D and Nishikawa, H and Hattori, M and Hino, Y and Ikegawa, S and Yamamoto, K and Toya, T and Doki, N and Koizumi, K and Honda, K and Ohashi, K}, title = {Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut.}, journal = {Blood}, volume = {128}, number = {16}, pages = {2083-2088}, pmid = {27461930}, issn = {1528-0020}, mesh = {Acute Disease ; Adult ; Allografts ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Graft vs Host Disease/immunology/microbiology/pathology/*therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunocompromised Host ; Intestinal Diseases/immunology/microbiology/pathology/*therapy ; Leukemia, Myeloid, Acute/immunology/microbiology/pathology/therapy ; Male ; Middle Aged ; Pilot Projects ; T-Lymphocytes, Regulatory/immunology/pathology ; }, abstract = {Increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (aGVHD) in stem cell transplantation (SCT). Fecal microbiota transplantation (FMT) could represent an alternative treatment option for aGVHD. However, FMT for SCT patients carries a potential risk of infection by infused microbiota because of the severely immunosuppressed status. We therefore conducted a pilot study to evaluate the safety of FMT in SCT. A total of 4 patients with steroid-resistant (n = 3) or steroid-dependent gut aGVHD (n = 1) received FMT. No severe adverse events attributed to FMT were observed. All patients responded to FMT, with 3 complete responses and 1 partial response. Temporal dynamics of microbiota seemed to be linked to the gut condition of patients and peripheral effector regulatory T cells also increased during response to FMT. FMT was safely performed in our patients and might offer a novel therapeutic option for aGVHD. This trial was registered at the University Hospital Medical Information Network (https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000017575) as #UMIN000015115.}, }
@article {pmid27461176, year = {2016}, author = {Pigneur, B and Sokol, H}, title = {Fecal microbiota transplantation in inflammatory bowel disease: the quest for the holy grail.}, journal = {Mucosal immunology}, volume = {9}, number = {6}, pages = {1360-1365}, pmid = {27461176}, issn = {1935-3456}, mesh = {Animals ; Colitis, Ulcerative/etiology/therapy ; Crohn Disease/etiology/therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Feces/microbiology ; Humans ; Inflammatory Bowel Diseases/etiology/*therapy ; Microbiota ; Time Factors ; Tissue Donors ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease (IBD) is due to an aberrant immune response toward luminal antigens, probably commensal bacteria, in genetically susceptible subjects and is also influenced by environmental factors. An imbalanced intestinal microbiota known as "dysbiosis," characterized by an increased proportion of pro-inflammatory microorganisms and a decreased proportion of anti-inflammatory microorganisms, has been repeatedly observed in IBD and is now recognized as a key factor in the gut inflammatory process. Fecal microbiota transplantation (FMT) has gained interest as a novel treatment option in IBD. The goal of FMT in IBD is not only to correct the dysbiosis, but also to restore a normal dialog between the host immune system and the microbiota. Data are still scarce, but the results of the first studies suggest that FMT could be a promising therapy in IBD. More studies are needed to define the best indications, optimal timing, frequency, mode of delivery, and the optimal donor for each patient.}, }
@article {pmid27453747, year = {2016}, author = {Oprita, R and Bratu, M and Oprita, B and Diaconescu, B}, title = {Fecal transplantation - the new, inexpensive, safe, and rapidly effective approach in the treatment of gastrointestinal tract diseases.}, journal = {Journal of medicine and life}, volume = {9}, number = {2}, pages = {160-162}, pmid = {27453747}, issn = {1844-3117}, mesh = {Anti-Bacterial Agents/pharmacology ; Clostridioides difficile/drug effects ; Clostridium Infections/*therapy ; Drug Resistance, Bacterial ; *Fecal Microbiota Transplantation ; Gastrointestinal Diseases/*therapy ; Humans ; Prospective Studies ; Treatment Outcome ; }, abstract = {Introduction. Fecal transplantation was shown to effectively reduce the reoccurrence in patients with refractory Clostridium difficile infection. New data suggest that fecal transplantation could also be efficient in other gastrointestinal diseases, for instance in inflammatory bowel disease, irritable bowel syndrome, but, there are also some data that could imply the efficacy outside the gastrointestinal tract. Fecal transplantation should be considered a unique agent, capable of treating severe diseases, with essentially no adverse reactions, presenting a cure rate of over 90%. Materials and methods. This prospective study included 33 patients, of whom 28 patients with recurrent or resistant Clostridium difficile infection, who failed to be treated with conventional therapy, which presupposed vancomycin administration and 5 patients with inflammatory bowel disease, more precisely with ulcerative colitis, refractory on biologic agents (infliximab and adalimumab). In most of the cases, fecal transplant was realized with the infusion of stool through colonoscopy. Results. Most of the patients from both groups (Clostridium difficile infection and Ulcerative Colitis) responded (31 patients) with a total relief of the symptoms, after 1 FMT for Clostridium difficile group and after more than one for the ulcerative colitis group. The so-called primary cure rate was 96.42% for Clostridium group. For ulcerative colitis, group 3 of the patients needed 3 or 4 infusions for symptom relief. One patient was categorized as non-responsive (patient with UC) and needed surgery. Due to non-fecal transplant related causes, one death was reported. Conclusions. Fecal transplant is highly effective, safe, with practically no adverse effects, inexpensive, a procedure easy to be done that could be introduced in Clostridium difficile treatment protocols. As for ulcerative colitis treatment with FMT, future randomized controlled trials are needed to prove its efficiency.}, }
@article {pmid27452730, year = {2016}, author = {Schulz-Stübner, S and Textor, Z and Anetseder, M}, title = {Fecal Microbiota Therapy as Rescue Therapy for Life-Threatening Clostridium difficile Infection in the Critically Ill: A Small Case Series.}, journal = {Infection control and hospital epidemiology}, volume = {37}, number = {9}, pages = {1129-1131}, doi = {10.1017/ice.2016.158}, pmid = {27452730}, issn = {1559-6834}, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; Critical Illness ; *Fecal Microbiota Transplantation ; Humans ; Retrospective Studies ; Treatment Outcome ; }, }
@article {pmid27449598, year = {2016}, author = {Hwang, IY and Koh, E and Kim, HR and Yew, WS and Chang, MW}, title = {Reprogrammable microbial cell-based therapeutics against antibiotic-resistant bacteria.}, journal = {Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy}, volume = {27}, number = {}, pages = {59-71}, doi = {10.1016/j.drup.2016.06.002}, pmid = {27449598}, issn = {1532-2084}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antimicrobial Cationic Peptides/biosynthesis/*therapeutic use ; Bacteria/*drug effects/genetics/pathogenicity ; Bacterial Infections/microbiology/pathology/*therapy ; Bacteriophages/genetics/metabolism ; Cell Engineering/*methods ; Drug Resistance, Bacterial/genetics ; Dysbiosis/microbiology/pathology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics ; Humans ; }, abstract = {The discovery of antimicrobial drugs and their subsequent use has offered an effective treatment option for bacterial infections, reducing morbidity and mortality over the past 60 years. However, the indiscriminate use of antimicrobials in the clinical, community and agricultural settings has resulted in selection for multidrug-resistant bacteria, which has led to the prediction of possible re-entrance to the pre-antibiotic era. The situation is further exacerbated by significantly reduced antimicrobial drug discovery efforts by large pharmaceutical companies, resulting in a steady decline in the number of new antimicrobial agents brought to the market in the past several decades. Consequently, there is a pressing need for new antimicrobial therapies that can be readily designed and implemented. Recently, it has become clear that the administration of broad-spectrum antibiotics can lead to collateral damage to the human commensal microbiota, which plays several key roles in host health. Advances in genetic engineering have opened the possibility of reprogramming commensal bacteria that are in symbiotic existence throughout the human body to implement antimicrobial drugs with high versatility and efficacy against pathogenic bacteria. In this review, we discuss recent advances and potentialities of engineered bacteria in providing a novel antimicrobial strategy against antibiotic resistance.}, }
@article {pmid27447476, year = {2016}, author = {Girotra, M and Garg, S and Anand, R and Song, Y and Dutta, SK}, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in the Elderly: Long-Term Outcomes and Microbiota Changes.}, journal = {Digestive diseases and sciences}, volume = {61}, number = {10}, pages = {3007-3015}, pmid = {27447476}, issn = {1573-2568}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Bacterial Toxins/genetics ; Clostridioides difficile/genetics ; Enterocolitis, Pseudomembranous/*therapy ; Enterotoxins/analysis ; Enzyme-Linked Immunosorbent Assay ; *Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Female ; Firmicutes/genetics ; Gastrointestinal Microbiome/*genetics ; Humans ; Longitudinal Studies ; Male ; Prospective Studies ; Proteobacteria/genetics ; RNA, Ribosomal, 16S/*genetics ; Recurrence ; Sequence Analysis, RNA ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) has become the cornerstone in management of recurrent Clostridium difficile infection (RCDI) in adults. However, data on efficacy, safety, long-term outcomes, and microbiota alterations are limited in elderly patients (>65 years).<br><br>METHODS: Twenty-nine consecutive elderly patients with RCDI underwent FMT with combined jejunal and colonic method and monitored for long-term outcomes. Fecal samples from five elderly RCDI patients (G65) were subjected to genomic analysis before and after FMT, and microbiota changes were compared with matched RCDI patients below 65&#xa0;years (L65).<br><br>RESULTS: FMT resulted in marked improvement in all clinical parameters, including abdominal pain, bloating, and diarrhea in all elderly RCDI patients. Fecal C. difficile toxin was positive in all 29 patients and turned negative in all 27 patients, who agreed to undergo this test after FMT. Statistically significant improvement in leukocytosis was noted (p&#xa0;<&#xa0;0.05). Only adverse events reported were transient mild fever (2/29) and bloating (3/29). Long-term follow-up over 25.4&#xa0;&#xb1;&#xa0;12.8&#xa0;months did not reveal any additional adverse events or RCDI recurrence. Genomic analysis suggested that overall microbiota diversity increased post-FMT in elderly RCDI patients. However, this response was less robust than the younger group. While Firmicutes did not change markedly, Proteobacteria decreased significantly in post-FMT samples in elderly RCDI patients.<br><br>CONCLUSIONS: These observations suggest that FMT in elderly patients with RCDI appears to be highly efficacious with no recurrence of infection over long-term follow-up. Alterations in microbiota in this group of patients are characterized by less robust increase in microbial diversity and marked reduction in phylum Proteobacteria.}, }
@article {pmid27444041, year = {2016}, author = {Kim, D and Yoo, SA and Kim, WU}, title = {Gut microbiota in autoimmunity: potential for clinical applications.}, journal = {Archives of pharmacal research}, volume = {39}, number = {11}, pages = {1565-1576}, doi = {10.1007/s12272-016-0796-7}, pmid = {27444041}, issn = {1976-3786}, mesh = {Animals ; Anti-Infective Agents/administration &amp; dosage/therapeutic use ; Autoimmune Diseases/immunology/*microbiology/prevention &amp; control ; Dysbiosis/diet therapy/drug therapy/*immunology/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*immunology ; Host-Pathogen Interactions/immunology ; Humans ; Intestines/*microbiology ; Probiotics/administration &amp; dosage/therapeutic use ; }, abstract = {Microbial habitation in the human body begins immediately after birth, and adults are colonized by microbes outnumbering human cells by a factor of ten. Especially, intestinal track is a living space for diverse microbial species that have coevolved symbiotically. A principal function of the gut microbiota is to protect the host from harmful bacteria and to provide benefits for the host through several mechanisms, including direct competition for limited nutrients, training of host immune systems to recognize specifically foreign materials and conversion of otherwise indigestible food into energy and absorbable nutrients. Therefore, gut dysbiosis, a bacterial imbalance state, is related with the pathogenesis of various host diseases including autoimmune diseases. In the current review, we highlight the importance of gut microbiota in the normal health and autoimmune diseases. We also discuss regulation of gut dysbiosis and future direction for potential clinical applications, including treatment and diagnostics of autoimmune diseases.}, }
@article {pmid27428728, year = {2016}, author = {Terveer, EM and van Beurden, YH and van Dorp, S and Keller, JJ and Kuijper, EJ}, title = {Is the Lower Gastrointestinal Route Really Preferred Over the Upper Gastrointestinal Route for Fecal Microbiota Transfer?.}, journal = {Journal of clinical gastroenterology}, volume = {50}, number = {10}, pages = {895}, doi = {10.1097/MCG.0000000000000595}, pmid = {27428728}, issn = {1539-2031}, mesh = {Fecal Microbiota Transplantation ; *Feces ; Gastrointestinal Tract ; Humans ; *Microbiota ; }, }
@article {pmid27419166, year = {2016}, author = {Navalkele, BD and Lerner, SA}, title = {Intravenous Tigecycline Facilitates Cure of Severe Clostridium difficile Infection (CDI) After Failure of Standard Therapy: A Case Report and Literature Review of Tigecycline Use in CDI.}, journal = {Open forum infectious diseases}, volume = {3}, number = {2}, pages = {ofw094}, pmid = {27419166}, issn = {2328-8957}, abstract = {Standard treatment for severe Clostridium difficile infection (CDI) is oral vancomycin with metronidazole. After failure of this standard regimen, treatment becomes challenging. A young woman treated for septic shock developed CDI. Standard treatment failed and she was ineligible for fecal transplant. Addition of tigecycline to her regimen resulted in cure.}, }
@article {pmid27418314, year = {2016}, author = {Murakami, M and Tognini, P and Liu, Y and Eckel-Mahan, KL and Baldi, P and Sassone-Corsi, P}, title = {Gut microbiota directs PPARγ-driven reprogramming of the liver circadian clock by nutritional challenge.}, journal = {EMBO reports}, volume = {17}, number = {9}, pages = {1292-1303}, pmid = {27418314}, issn = {1469-3178}, support = {R21 DA036408/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Blood Glucose ; *Circadian Clocks/drug effects/genetics ; Circadian Rhythm ; Cluster Analysis ; *Diet, High-Fat ; Energy Metabolism/genetics ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Gene Expression Profiling ; Humans ; Liver/*metabolism ; Male ; Mice ; PPAR gamma/*metabolism ; Signal Transduction ; }, abstract = {The liver circadian clock is reprogrammed by nutritional challenge through the rewiring of specific transcriptional pathways. As the gut microbiota is tightly connected to host metabolism, whose coordination is governed by the circadian clock, we explored whether gut microbes influence circadian homeostasis and how they distally control the peripheral clock in the liver. Using fecal transplant procedures we reveal that, in response to high-fat diet, the gut microbiota drives PPARγ-mediated activation of newly oscillatory transcriptional programs in the liver. Moreover, antibiotics treatment prevents PPARγ-driven transcription in the liver, underscoring the essential role of gut microbes in clock reprogramming and hepatic circadian homeostasis. Thus, a specific molecular signature characterizes the influence of the gut microbiome in the liver, leading to the transcriptional rewiring of hepatic metabolism.}, }
@article {pmid27415182, year = {2016}, author = {Li, M and Li, Z and Wen, S and Liu, Y and Wang, Y and Tang, L}, title = {Transplantation of a bacterial consortium ameliorates trinitrobenzenesulfonic acid-induced colitis and intestinal dysbiosis in rats.}, journal = {Future microbiology}, volume = {11}, number = {}, pages = {887-902}, doi = {10.2217/fmb-2015-0002}, pmid = {27415182}, issn = {1746-0921}, mesh = {Animals ; Colitis/chemically induced/microbiology/*therapy ; Colon/immunology/microbiology/pathology ; Cytokines/immunology ; Disease Models, Animal ; Dysbiosis/chemically induced/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/therapy ; Intestines/immunology/microbiology/pathology ; Mice ; *Microbial Consortia ; Peroxidase/metabolism ; Rats ; Trinitrobenzenesulfonic Acid/*administration &amp; dosage ; }, abstract = {AIM: To investigate the effects of a defined bacterial consortium on trinitrobenzenesulfonic acid (TNBS)-induced colitis and intestinal dysbiosis in rats.<br><br>MATERIALS &amp; METHODS: Rats with TNBS-induced colitis were treated with ceftriaxone and/or a mixture of ten bacterial strains isolated from mouse feces for continuous 24 days. Macroscopic and histopathological parameters in colonic tissue were compared, as were myeloperoxidase enzyme activity and cytokine levels. Patterns of intestinal microbiota were assessed by PCR-denaturing gradient gel electrophoresis, the abundance of selected microbial groups was evaluated by qPCR.<br><br>RESULTS &amp; CONCLUSION: Transplantation of the bacterial consortium showed anti-inflammatory activity in the intestines of rats with TNBS-induced colitis and contributed to the rapid re-establishment of intestinal microbial equilibrium. A defined bacterial consortium may be a viable therapeutic option for the treatment inflammatory bowel disease.}, }
@article {pmid27413153, year = {2016}, author = {Singh, V and Roth, S and Llovera, G and Sadler, R and Garzetti, D and Stecher, B and Dichgans, M and Liesz, A}, title = {Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {36}, number = {28}, pages = {7428-7440}, pmid = {27413153}, issn = {1529-2401}, mesh = {Animals ; Brain Infarction/etiology ; CD3 Complex/metabolism ; Disease Models, Animal ; Dysbiosis/*etiology/immunology/microbiology ; Encephalitis/*complications/*etiology ; Feces/microbiology ; Female ; Gastrointestinal Diseases/etiology ; Gastrointestinal Motility/physiology ; Homeodomain Proteins/genetics/metabolism ; Ileus/immunology/microbiology/pathology ; Infarction, Middle Cerebral Artery/complications ; Leukocytes/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microbiota/immunology/*physiology ; Stroke/*complications/etiology ; Tertiary Lymphoid Structures/pathology ; }, abstract = {UNLABELLED: Acute brain ischemia induces a local neuroinflammatory reaction and alters peripheral immune homeostasis at the same time. Recent evidence has suggested a key role of the gut microbiota in autoimmune diseases by modulating immune homeostasis. Therefore, we investigated the mechanistic link among acute brain ischemia, microbiota alterations, and the immune response after brain injury. Using two distinct models of acute middle cerebral artery occlusion, we show by next-generation sequencing that large stroke lesions cause gut microbiota dysbiosis, which in turn affects stroke outcome via immune-mediated mechanisms. Reduced species diversity and bacterial overgrowth of bacteroidetes were identified as hallmarks of poststroke dysbiosis, which was associated with intestinal barrier dysfunction and reduced intestinal motility as determined by in vivo intestinal bolus tracking. Recolonizing germ-free mice with dysbiotic poststroke microbiota exacerbates lesion volume and functional deficits after experimental stroke compared with the recolonization with a normal control microbiota. In addition, recolonization of mice with a dysbiotic microbiome induces a proinflammatory T-cell polarization in the intestinal immune compartment and in the ischemic brain. Using in vivo cell-tracking studies, we demonstrate the migration of intestinal lymphocytes to the ischemic brain. Therapeutic transplantation of fecal microbiota normalizes brain lesion-induced dysbiosis and improves stroke outcome. These results support a novel mechanism in which the gut microbiome is a target of stroke-induced systemic alterations and an effector with substantial impact on stroke outcome.<br><br>SIGNIFICANCE STATEMENT: We have identified a bidirectional communication along the brain-gut microbiota-immune axis and show that the gut microbiota is a central regulator of immune homeostasis. Acute brain lesions induced dysbiosis of the microbiome and, in turn, changes in the gut microbiota affected neuroinflammatory and functional outcome after brain injury. The microbiota impact on immunity and stroke outcome was transmissible by microbiota transplantation. Our findings support an emerging concept in which the gut microbiota is a key regulator in priming the neuroinflammatory response to brain injury. These findings highlight the key role of microbiota as a potential therapeutic target to protect brain function after injury.}, }
@article {pmid27411009, year = {2016}, author = {Reijnders, D and Goossens, GH and Hermes, GD and Neis, EP and van der Beek, CM and Most, J and Holst, JJ and Lenaerts, K and Kootte, RS and Nieuwdorp, M and Groen, AK and Olde Damink, SW and Boekschoten, MV and Smidt, H and Zoetendal, EG and Dejong, CH and Blaak, EE}, title = {Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial.}, journal = {Cell metabolism}, volume = {24}, number = {1}, pages = {63-74}, doi = {10.1016/j.cmet.2016.06.016}, pmid = {27411009}, issn = {1932-7420}, mesh = {Adipocytes/drug effects/metabolism/pathology ; Adult ; Aged ; Amoxicillin/pharmacology ; Anti-Bacterial Agents/*pharmacology ; Biomarkers/metabolism ; Butyric Acid/blood ; Cell Shape/drug effects ; Double-Blind Method ; Energy Metabolism/drug effects ; Feces/chemistry ; Gastrointestinal Microbiome/*drug effects ; Gene Expression Regulation/drug effects ; Humans ; Inflammation/pathology ; Insulin/pharmacology ; Male ; Middle Aged ; Obesity/genetics/*metabolism/*microbiology ; Organ Specificity/drug effects ; Permeability ; Placebos ; Substrate Specificity/drug effects ; Vancomycin/pharmacology ; }, abstract = {The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans.}, }
@article {pmid27407273, year = {2016}, author = {Leszczyszyn, JJ and Radomski, M and Leszczyszyn, AM}, title = {Intestinal microbiota transplant - current state of knowledge.}, journal = {Reumatologia}, volume = {54}, number = {1}, pages = {24-28}, pmid = {27407273}, issn = {0034-6233}, abstract = {Faecal microbiota transplantation (FMT) has induced a lot scientific interest and hopes for the last couple of years. FMT has been approved as a treatment of recurrent Clostridium difficile colitis. Highly sophisticated molecular DNA identification methods have been used to assess the healthy human microbiome as well as its disturbances in several diseases. The metabolic and immunologic functions of the microbiome have become more clear and understandable. A lot of pathological changes, such as production of short-chain fatty acids or components of the inflammatory cascade, caused by changes in microbiome diversity, variability and richness have been observed among patients suffering from inflammatory bowel diseases, irritable bowel syndrome, type 2 diabetes or rheumatoid arthritis. The published clinical results are encouraging, but still there is huge demand for FMT controlled clinical trials.}, }
@article {pmid27404502, year = {2016}, author = {Bojanova, DP and Bordenstein, SR}, title = {Fecal Transplants: What Is Being Transferred?.}, journal = {PLoS biology}, volume = {14}, number = {7}, pages = {e1002503}, pmid = {27404502}, issn = {1545-7885}, mesh = {Animals ; Enterocolitis, Pseudomembranous/therapy ; Fatty Acids/metabolism ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; }, abstract = {Fecal transplants are increasingly utilized for treatment of recurrent infections (i.e., Clostridium difficile) in the human gut and as a general research tool for gain-of-function experiments (i.e., gavage of fecal pellets) in animal models. Changes observed in the recipient's biology are routinely attributed to bacterial cells in the donor feces (~1011 per gram of human wet stool). Here, we examine the literature and summarize findings on the composition of fecal matter in order to raise cautiously the profile of its multipart nature. In addition to viable bacteria, which may make up a small fraction of total fecal matter, other components in unprocessed human feces include colonocytes (~107 per gram of wet stool), archaea (~108 per gram of wet stool), viruses (~108 per gram of wet stool), fungi (~106 per gram of wet stool), protists, and metabolites. Thus, while speculative at this point and contingent on the transplant procedure and study system, nonbacterial matter could contribute to changes in the recipient's biology. There is a cautious need for continued reductionism to separate out the effects and interactions of each component.}, }
@article {pmid27393975, year = {2016}, author = {Phan, TG and Dreno, B and da Costa, AC and Li, L and Orlandi, P and Deng, X and Kapusinszky, B and Siqueira, J and Knol, AC and Halary, F and Dantal, J and Alexander, KA and Pesavento, PA and Delwart, E}, title = {A new protoparvovirus in human fecal samples and cutaneous T cell lymphomas (mycosis fungoides).}, journal = {Virology}, volume = {496}, number = {}, pages = {299-305}, doi = {10.1016/j.virol.2016.06.013}, pmid = {27393975}, issn = {1096-0341}, support = {R01 HL105770/HL/NHLBI NIH HHS/United States ; }, mesh = {Biopsy ; DNA, Viral ; Feces/*virology ; Humans ; Metagenome ; Metagenomics ; Mycosis Fungoides/*etiology/pathology ; Open Reading Frames ; Parvoviridae Infections/complications/*virology ; Parvovirus/*classification/*genetics/isolation &amp; purification ; Phylogeny ; RNA Splicing ; }, abstract = {We genetically characterized seven nearly complete genomes in the protoparvovirus genus from the feces of children with diarrhea. The viruses, provisionally named cutaviruses (CutaV), varied by 1-6% nucleotides and shared ~76% and ~82% amino acid identity with the NS1 and VP1 of human bufaviruses, their closest relatives. Using PCR, cutavirus DNA was found in 1.6% (4/245) and 1% (1/100) of diarrhea samples from Brazil and Botswana respectively. In silico analysis of pre-existing metagenomics datasets then revealed closely related parvovirus genomes in skin biopsies from patients with epidermotropic cutaneous T-cell lymphoma (CTCL or mycosis fungoides). PCR of skin biopsies yielded cutavirus DNA in 4/17 CTCL, 0/10 skin carcinoma, and 0/21 normal or noncancerous skin biopsies. In situ hybridization of CTCL skin biopsies detected viral genome within rare individual cells in regions of neoplastic infiltrations. The influence of cutavirus infection on human enteric functions and possible oncolytic role in CTCL progression remain to be determined.}, }
@article {pmid27391011, year = {2016}, author = {Brittnacher, MJ and Heltshe, SL and Hayden, HS and Radey, MC and Weiss, EJ and Damman, CJ and Zisman, TL and Suskind, DL and Miller, SI}, title = {GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota Transplantation Analysis.}, journal = {PloS one}, volume = {11}, number = {7}, pages = {e0158897}, pmid = {27391011}, issn = {1932-6203}, support = {P30 DK089507/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Child ; *Crohn Disease/genetics/microbiology/therapy ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; *Living Donors ; Male ; *Metagenome ; *Metagenomics ; *Sequence Alignment ; }, abstract = {BACKGROUND: Comparative analysis of gut microbiomes in clinical studies of human diseases typically rely on identification and quantification of species or genes. In addition to exploring specific functional characteristics of the microbiome and potential significance of species diversity or expansion, microbiome similarity is also calculated to study change in response to therapies directed at altering the microbiome. Established ecological measures of similarity can be constructed from species abundances, however methods for calculating these commonly used ecological measures of similarity directly from whole genome shotgun (WGS) metagenomic sequence are lacking.<br><br>RESULTS: We present an alignment-free method for calculating similarity of WGS metagenomic sequences that is analogous to the Bray-Curtis index for species, implemented by the General Utility for Testing Sequence Similarity (GUTSS) software application. This method was applied to intestinal microbiomes of healthy young children to measure developmental changes toward an adult microbiome during the first 3 years of life. We also calculate similarity of donor and recipient microbiomes to measure establishment, or engraftment, of donor microbiota in fecal microbiota transplantation (FMT) studies focused on mild to moderate Crohn's disease. We show how a relative index of similarity to donor can be calculated as a measure of change in a patient's microbiome toward that of the donor in response to FMT.<br><br>CONCLUSION: Because clinical efficacy of the transplant procedure cannot be fully evaluated without analysis methods to quantify actual FMT engraftment, we developed a method for detecting change in the gut microbiome that is independent of species identification and database bias, sensitive to changes in relative abundance of the microbial constituents, and can be formulated as an index for correlating engraftment success with clinical measures of disease. More generally, this method may be applied to clinical evaluation of human microbiomes and provide potential diagnostic determination of individuals who may be candidates for specific therapies directed at alteration of the microbiome.}, }
@article {pmid27387020, year = {2016}, author = {Ge, X and Tian, H and Ding, C and Gu, L and Wei, Y and Gong, J and Zhu, W and Li, N and Li, J}, title = {Fecal Microbiota Transplantation in Combination with Soluble Dietary Fiber for Treatment of Slow Transit Constipation: A Pilot Study.}, journal = {Archives of medical research}, volume = {47}, number = {3}, pages = {236-242}, doi = {10.1016/j.arcmed.2016.06.005}, pmid = {27387020}, issn = {1873-5487}, mesh = {Adult ; Aged ; Constipation/physiopathology/*therapy ; Defecation ; Dietary Fiber/*therapeutic use ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Transit ; Humans ; Male ; Middle Aged ; Pilot Projects ; }, abstract = {BACKGROUND AND AIMS: Intestinal microbiota and soluble dietary fiber play an important role in intestinal microecology, which is closely related to gut motility. Regulating intestinal microecology comprised of fecal microbiota transplantation (FMT) or fiber supplementation is becoming a novel therapy for functional gastrointestinal disease. We launched this study to evaluate the efficacy and safety of FMT combined with fiber for slow transit constipation (STC).<br><br>METHODS: We performed a study of 21 patients with STC. Participants received FMT (via&#xa0;nasojejunal tubes) on 3 consecutive days. After FMT, they were recommended to receive soluble dietary fiber for 4&#xa0;weeks (8&#xa0;g, twice daily). Rate of clinical improvement and remission, constipation-related symptoms (PAC-SYM scores), bowel movements per week, colonic transit time (CTT) and gastrointestinal quality-of-life index (GIQLI) were recorded during the 12-week follow-up.<br><br>RESULTS: At the study end, clinical improvement and remission of constipated patients reached 66.7 and 42.9%, respectively. The patients showed an increased stool frequency from 1.7&#xa0;&#xb1;&#xa0;0.5 per week to 4.8&#xa0;&#xb1;&#xa0;2.1 per week (p <0.05) and an improved stool consistency after FMT combined with fiber. When compared to pre-treatment, PAC-SYM scores improved significantly from 2.0&#xa0;&#xb1;&#xa0;0.4 to 1.5&#xa0;&#xb1;&#xa0;0.6 after treatment (p <0.05). Meanwhile, patients showed an acceleration of colonic transit time from 81.9&#xa0;&#xb1;&#xa0;9.5 to 53.5&#xa0;&#xb1;&#xa0;11.2&#xa0;h at week 12. During follow-up, patients felt satisfied with improved GIQLI. No serious adverse events were observed.<br><br>CONCLUSION: This is a pilot study confirming that FMT combined with fiber may improve symptoms experienced by constipated patients by regulating intestinal microecology, without any serious adverse events.}, }
@article {pmid27382953, year = {2016}, author = {Gutiérrez-Delgado, EM and Garza-González, E and Martínez-Vázquez, MA and González-González, JA and Maldonado-Garza, HJ and Mendoza-Olazaran, S and Hernández-Balboa, CL and Camacho-Ortiz, A}, title = {Fecal transplant for Clostridium difficile infection relapses using "pooled" frozen feces from non-related donors.}, journal = {Acta gastro-enterologica Belgica}, volume = {79}, number = {2}, pages = {268-270}, pmid = {27382953}, issn = {1784-3227}, mesh = {Adult ; Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; }, }
@article {pmid27371370, year = {2016}, author = {Eppinga, H and Fuhler, GM and Peppelenbosch, MP and Hecht, GA}, title = {Gut Microbiota Developments With Emphasis on Inflammatory Bowel Disease: Report From the Gut Microbiota for Health World Summit 2016.}, journal = {Gastroenterology}, volume = {151}, number = {2}, pages = {e1-4}, doi = {10.1053/j.gastro.2016.06.024}, pmid = {27371370}, issn = {1528-0012}, mesh = {Diet/adverse effects ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/trends ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Probiotics/therapeutic use ; }, }
@article {pmid27367328, year = {2016}, author = {Atalay, A and Koc, AN and Akyol, G and Cakir, N and Kaynar, L and Ulu-Kilic, A}, title = {Pulmonary infection caused by Talaromyces purpurogenus in a patient with multiple myeloma.}, journal = {Le infezioni in medicina}, volume = {24}, number = {2}, pages = {153-157}, pmid = {27367328}, issn = {2532-8689}, mesh = {Acinetobacter Infections/complications ; Aged ; Antifungal Agents/therapeutic use ; Coinfection ; Fatal Outcome ; Female ; Humans ; Immunocompromised Host ; Lung Diseases, Fungal/complications/drug therapy/*microbiology ; Multiple Myeloma/*complications ; Opportunistic Infections/complications/drug therapy/*microbiology ; Plasmacytoma/complications/diagnosis ; Pulmonary Disease, Chronic Obstructive/complications ; Species Specificity ; Spinal Neoplasms/complications/diagnosis ; Sputum/microbiology ; Talaromyces/*isolation &amp; purification ; Thoracic Vertebrae ; Voriconazole/therapeutic use ; }, abstract = {A 66-year-old female patient with multiple myeloma (MM) was admitted to the emergency service on 29.09.2014 with an inability to walk, and urinary and faecal incontinence. She had previously undergone autologous bone marrow transplantation (ABMT) twice. The patient was hospitalized at the Department of Haematology. Further investigations showed findings suggestive of a spinal mass at the T5-T6-T7 level, and a mass lesion in the iliac fossa. The mass lesion was resected and needle biopsy was performed during a colonoscopy. Examination of the specimens revealed plasmacytoma. The patient also had chronic obstructive pulmonary disease (COPD) and was suffering from respiratory distress. After consultation with an infectious diseases specialist the patient was placed on an intravenous antibiotherapy with piperacillin/tazobactam (4.5g x 3) on 17.10.2014. During piperacillin/tazobactam treatment, the patient suffered from drowsiness, her general condition deteriorated, and she had rales on auscultation of the lungs. The patient underwent thoracic computerized tomography (CT) which showed areas of focal consolidation in the lower lobes of the two lungs (more prominent on the left), and increased medullary density. The radiology report suggested that fungal infection could not be ruled out based on the CT images. The sputum sample was sent to the mycology laboratory and direct microscopic examination performed with Gram and Giemsa staining showed the presence of septate hyphae; therefore voriconazole was added to the treatment. Slow growing (at day 10), grey-greenish colonies and red pigment formation were observed in all culture media except cycloheximide-containing Sabouraud dextrose agar (SDA) medium. The isolate was initially considered to be Talaromyces marneffei. However, it was subsequently identified by DNA sequencing analysis as Talaromyces purpurogenus. The patient was discharged at her own wish, as she was willing to continue treatment in her hometown. Unfortunately, the patient died on December 8, 2014. In conclusion, apart from T. marneffei, less common strains such as T. purpurogenus should be considered when clinical samples obtained from patients with haematologic/oncologic disorders show fungal colonies that form red pigments on the culture media and when microscopic examination suggests a morphological appearance similar to Penicillium species.}, }
@article {pmid27366225, year = {2016}, author = {McCarville, JL and Caminero, A and Verdu, EF}, title = {Novel perspectives on therapeutic modulation of the gut microbiota.}, journal = {Therapeutic advances in gastroenterology}, volume = {9}, number = {4}, pages = {580-593}, pmid = {27366225}, issn = {1756-283X}, abstract = {The gut microbiota contributes to the maintenance of health and, when disrupted, may drive gastrointestinal and extragastrointestinal disease. This can occur through direct pathways such as interaction with the epithelial barrier and mucosal immune system or indirectly via production of metabolites. There is no current curative therapy for chronic inflammatory conditions such as inflammatory bowel disease, which are complex multifactorial disorders involving genetic predisposition, and environmental triggers. Therapies are directed to suppress inflammation rather than the driver, and these approaches are not devoid of adverse effects. Therefore, there is great interest in modulation of the gut microbiota to provide protection from disease. Interventions that modulate the microbiota include diet, probiotics and more recently the emergence of experimental therapies such as fecal microbiota transplant or phage therapy. Emerging data indicate that certain bacteria can induce protective immune responses and enhance intestinal barrier function, which could be potential therapeutic targets. However, mechanistic links and specific therapeutic recommendations are still lacking. Here we provide a pathophysiological overview of potential therapeutic applications of the gut microbiota.}, }
@article {pmid27363238, year = {2016}, author = {Fatima, A and Sylvester, FA}, title = {The Gut Microbiome and Probiotics.}, journal = {Adolescent medicine: state of the art reviews}, volume = {27}, number = {1}, pages = {140-154}, pmid = {27363238}, issn = {1934-4287}, mesh = {Adolescent ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/*microbiology/therapy ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology/therapy ; Obesity/*microbiology/therapy ; Probiotics/*therapeutic use ; }, }
@article {pmid27358976, year = {2016}, author = {Polák, P}, title = {[Fecal microbiota transplantation].}, journal = {Vnitrni lekarstvi}, volume = {62}, number = {2}, pages = {92-94}, pmid = {27358976}, issn = {0042-773X}, }
@article {pmid27358035, year = {2016}, author = {Stöger, JL and Boshuizen, MC and Brufau, G and Gijbels, MJ and Wolfs, IM and van der Velden, S and Pöttgens, CC and Vergouwe, MN and Wijnands, E and Beckers, L and Goossens, P and Kerksiek, A and Havinga, R and Müller, W and Lütjohann, D and Groen, AK and de Winther, MP}, title = {Deleting myeloid IL-10 receptor signalling attenuates atherosclerosis in LDLR-/- mice by altering intestinal cholesterol fluxes.}, journal = {Thrombosis and haemostasis}, volume = {116}, number = {3}, pages = {565-577}, doi = {10.1160/TH16-01-0043}, pmid = {27358035}, issn = {2567-689X}, mesh = {Animals ; Apoptosis ; Atherosclerosis/etiology/*metabolism/prevention &amp; control ; Biological Transport, Active ; Cholesterol/*metabolism ; Cholesterol, Dietary/administration &amp; dosage ; Disease Models, Animal ; Female ; Hypercholesterolemia/prevention &amp; control ; Inflammation/etiology/metabolism/pathology ; Intestinal Mucosa/metabolism ; Macrophages/metabolism/pathology ; Mice ; Mice, Knockout ; Myeloid Cells/metabolism/pathology ; Plaque, Atherosclerotic/etiology/metabolism/pathology ; Receptors, Interleukin-10/*deficiency/genetics ; Receptors, LDL/*deficiency/genetics ; Signal Transduction ; Sterol O-Acyltransferase/metabolism ; Sterol O-Acyltransferase 2 ; }, abstract = {Inflammatory responses and cholesterol homeostasis are interconnected in atherogenesis. Interleukin (IL)-10 is an important anti-inflammatory cytokine, known to suppress atherosclerosis development. However, the specific cell types responsible for the atheroprotective effects of IL-10 remain to be defined and knowledge on the actions of IL-10 in cholesterol homeostasis is scarce. Here we investigated the functional involvement of myeloid IL-10-mediated atheroprotection. To do so, bone marrow from IL-10 receptor 1 (IL-10R1) wild-type and myeloid IL-10R1-deficient mice was transplanted to lethally irradiated female LDLR-/- mice. Hereafter, mice were given a high cholesterol diet for 10 weeks after which atherosclerosis development and cholesterol metabolism were investigated. In vitro, myeloid IL-10R1 deficiency resulted in a pro-inflammatory macrophage phenotype. However, in vivo significantly reduced lesion size and severity was observed. This phenotype was associated with lower myeloid cell accumulation and more apoptosis in the lesions. Additionally, a profound reduction in plasma and liver cholesterol was observed upon myeloid IL-10R1 deficiency, which was reflected in plaque lipid content. This decreased hypercholesterolaemia was associated with lowered very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels, likely as a response to decreased intestinal cholesterol absorption. In addition, IL-10R1 deficient mice demonstrated substantially higher faecal sterol loss caused by increased non-biliary cholesterol efflux. The induction of this process was linked to impaired ACAT2-mediated esterification of liver and plasma cholesterol. Overall, myeloid cells do not contribute to IL-10-mediated atheroprotection. In addition, this study demonstrates a novel connection between IL-10-mediated inflammation and cholesterol homeostasis in atherosclerosis. These findings make us reconsider IL-10 as a beneficial influence on atherosclerosis.}, }
@article {pmid27347881, year = {2016}, author = {Zhang, T and Cui, B and Li, P and He, Z and Long, C and Wei, L and Peng, Z and Ji, G and Zhang, F}, title = {Short-Term Surveillance of Cytokines and C-Reactive Protein Cannot Predict Efficacy of Fecal Microbiota Transplantation for Ulcerative Colitis.}, journal = {PloS one}, volume = {11}, number = {6}, pages = {e0158227}, pmid = {27347881}, issn = {1932-6203}, mesh = {Adult ; Biomarkers ; C-Reactive Protein/*metabolism ; Case-Control Studies ; Colitis, Ulcerative/diagnosis/*metabolism/*therapy ; Cytokines/blood/*metabolism ; *Fecal Microbiota Transplantation/methods ; Female ; Humans ; Inflammation Mediators ; Male ; Middle Aged ; Prognosis ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: There were no reports on predicting long-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). This study aimed to detect short-term changes of cytokines and C-reactive protein (CRP) in patients with UC undergoing FMT, and to evaluate the predictive value of CRP and cytokines for the long-term efficacy of FMT.<br><br>METHODS: Nineteen patients with moderate to severe UC (Mayo score &#x2265; 6) were treated with single fresh FMT through mid-gut. Serum samples were collected before and three days post-FMT. Clinical responses were evaluated by a minimum follow-up of three months. Patients with clinical improvement and remission at the assessment point of three-month were included as response group, while patients without clinical improvement or remission were included as non-response group. Serum concentrations of cytokines (IL-1&#x3b2;, IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, IFN-&#x3b3;, TNF, TNFR-1, TNFR-2, MCP-1, G-CSF, GM-CSF) and CRP were assayed to predict the clinical response of FMT.<br><br>RESULTS: In total, 10.5% (2/19) of patients achieved clinical remission and 47.4% (9/19) achieved clinical improvement (Response group, including clinical remission and clinical improvement), 42.1% (8/19) failed to benefit from FMT (Non-response group). In both Response group and Non-response group, the level of CRP at three days after FMT didn't show significant decrease compared with that before FMT (p>0.05). However, in Response group, CRP level at three months after FMT decreased significantly than that before FMT (p<0.05). Compared with healthy controls (n = 9), patients with UC showed a higher baseline level of serum IL-6, TNFR-2 and G-CSF, and a lower level of IL-2 and IL-4 (p<0.05). In both Response group and Non-response group, none of the eleven detectable cytokines showed a significant difference between the value at three days after FMT and that before FMT (p>0.05).<br><br>CONCLUSIONS: Patients with moderate to severe UC presented a complex disorder of cytokines. However, the efficacy of FMT for UC might not be predicted by the short-term surveillance of cytokines and CRP.}, }
@article {pmid27340191, year = {2017}, author = {Kummen, M and Hov, JR}, title = {Response to 'Faecal microbiota profiles as diagnostic biomarkers in primary sclerosing cholangitis' by Rühlemann et al.}, journal = {Gut}, volume = {66}, number = {4}, pages = {755-756}, doi = {10.1136/gutjnl-2016-312347}, pmid = {27340191}, issn = {1468-3288}, mesh = {Biomarkers ; *Cholangitis, Sclerosing ; Feces ; Humans ; *Microbiota ; }, }
@article {pmid27337475, year = {2016}, author = {Shin, JH and Chaves-Olarte, E and Warren, CA}, title = {Clostridium difficile Infection.}, journal = {Microbiology spectrum}, volume = {4}, number = {3}, pages = {}, pmid = {27337475}, issn = {2165-0497}, support = {T32 AI007046/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins/toxicity ; Bacterial Toxins/toxicity ; Clostridioides difficile/*pathogenicity ; Cross Infection/microbiology ; *Enterocolitis, Pseudomembranous/diagnosis/drug therapy/epidemiology/pathology ; Enterotoxins/toxicity ; Humans ; Probiotics/therapeutic use ; }, abstract = {Clostridium difficile is an anaerobic, Gram-positive, spore-forming, toxin-secreting bacillus that has long been recognized to be the most common etiologic pathogen of antibiotic-associated diarrhea. C. difficile infection (CDI) is now the most common cause of health care-associated infections in the United States and accounts for 12% of these infections (Magill SS et al., N Engl J Med370:1198-1208, 2014). Among emerging pathogens of public health importance in the United States, CDI has the highest population-based incidence, estimated at 147 per 100,000 (Lessa FC et al., N Engl J Med372:825-834, 2015). In a report on antimicrobial resistance, C. difficile has been categorized by the Centers for Disease Control and Prevention as one of three "urgent" threats (http://www.cdc.gov/drugresistance/threat-report-2013/). Although C. difficile was first described in the late 1970s, the past decade has seen the emergence of hypertoxigenic strains that have caused increased morbidity and mortality worldwide. Pathogenic strains, host susceptibility, and other regional factors vary and may influence the clinical manifestation and approach to intervention. In this article, we describe the global epidemiology of CDI featuring the different strains in circulation outside of North America and Europe where strain NAP1/027/BI/III had originally gained prominence. The elderly population in health care settings has been disproportionately affected, but emergence of CDI in children and healthy young adults in community settings has, likewise, been reported. New approaches in management, including fecal microbiota transplantation, are discussed.}, }
@article {pmid27329806, year = {2016}, author = {Khoruts, A and Sadowsky, MJ}, title = {Understanding the mechanisms of faecal microbiota transplantation.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {13}, number = {9}, pages = {508-516}, pmid = {27329806}, issn = {1759-5053}, support = {R21 AI114722/AI/NIAID NIH HHS/United States ; }, mesh = {Bile Acids and Salts/metabolism ; *Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Forecasting ; Gastrointestinal Microbiome/physiology ; Humans ; }, abstract = {This Review summarizes mechanistic investigations in faecal microbiota transplantation (FMT), which has increasingly been adapted into clinical practice as treatment for Clostridium difficile infection (CDI) that cannot be eliminated with antibiotics alone. Administration of healthy donor faecal microbiota in this clinical situation results in its engraftment and restoration of normal gut microbial community structure and functionality. In this Review, we consider several main mechanisms for FMT effectiveness in treatment of CDI, including direct competition of C. difficile with commensal microbiota delivered by FMT, restoration of secondary bile acid metabolism in the colon and repair of the gut barrier by stimulation of the mucosal immune system. Some of these mechanistic insights suggest possibilities for developing novel, next-generation CDI therapeutics. FMT might also have potential applications for non-CDI indications. The gut can become a reservoir of other potential antibiotic-resistant pathogens under pressure of antibiotic treatments, and restoration of normal microbial community structure by FMT might be a promising approach to protect against infections with these pathogens as well. Finally, FMT could be considered for multiple chronic diseases that are associated with some form of dysbiosis. However, considerable research is needed to optimize the FMT protocols for such applications before their therapeutic promise can be evaluated.}, }
@article {pmid27329048, year = {2016}, author = {Stämmler, F and Gläsner, J and Hiergeist, A and Holler, E and Weber, D and Oefner, PJ and Gessner, A and Spang, R}, title = {Adjusting microbiome profiles for differences in microbial load by spike-in bacteria.}, journal = {Microbiome}, volume = {4}, number = {1}, pages = {28}, pmid = {27329048}, issn = {2049-2618}, mesh = {Animals ; Bacteria/*classification/genetics ; Bacteriological Techniques/methods ; DNA, Ribosomal/genetics ; Feces/*microbiology ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Mice ; Microbiota ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Next-generation 16S ribosomal RNA gene sequencing is widely used to determine the relative composition of the mammalian gut microbiomes. However, in the absence of a reference, this does not reveal alterations in absolute abundance of specific operational taxonomic units if microbial loads vary across specimens.<br><br>RESULTS: Here we suggest the spiking of exogenous bacteria into crude specimens to quantify ratios of absolute bacterial abundances. We use the 16S rDNA read counts of the spike-in bacteria to adjust the read counts of endogenous bacteria for changes in total microbial loads. Using a series of dilutions of pooled faecal samples from mice containing defined amounts of the spike-in bacteria Salinibacter ruber, Rhizobium radiobacter and Alicyclobacillus acidiphilus, we demonstrate that spike-in-based calibration to microbial loads allows accurate estimation of ratios of absolute endogenous bacteria abundances. Applied to stool specimens of patients undergoing allogeneic stem cell transplantation, we were able to determine changes in both relative and absolute abundances of various phyla, especially the genus Enterococcus, in response to antibiotic treatment and radio-chemotherapeutic conditioning.<br><br>CONCLUSION: Exogenous spike-in bacteria in gut microbiome studies enable estimation of ratios of absolute OTU abundances, providing novel insights into the structure and the dynamics of intestinal microbiomes.}, }
@article {pmid27328811, year = {2016}, author = {Mazzanti, B and Lorenzi, B and Borghini, A and Boieri, M and Ballerini, L and Saccardi, R and Weber, E and Pessina, F}, title = {Local injection of bone marrow progenitor cells for the treatment of anal sphincter injury: in-vitro expanded versus minimally-manipulated cells.}, journal = {Stem cell research &amp; therapy}, volume = {7}, number = {1}, pages = {85}, pmid = {27328811}, issn = {1757-6512}, mesh = {Anal Canal/injuries/*surgery ; Animals ; Bone Marrow Cells/*cytology/physiology ; Disease Models, Animal ; Fecal Incontinence/physiopathology/*therapy ; Genes, Reporter ; Humans ; Leukocytes, Mononuclear/*cytology/physiology/transplantation ; Male ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*cytology/physiology ; Muscle Contraction/physiology ; Rats ; Rats, Inbred Lew ; Regeneration/physiology ; Sphincterotomy, Endoscopic ; }, abstract = {BACKGROUND: Anal incontinence is a disabling condition that adversely affects the quality of life of a large number of patients, mainly with anal sphincter lesions. In a previous experimental work, in-vitro expanded bone marrow (BM)-derived mesenchymal stem cells (MSC) were demonstrated to enhance sphincter healing after injury and primary repair in a rat preclinical model. In the present article we investigated whether unexpanded BM mononuclear cells (MNC) may also be effective.<br><br>METHODS: Thirty-two rats, divided into groups, underwent sphincterotomy and repair (SR) with primary suture of anal sphincters plus intrasphincteric injection of saline (CTR), or of in-vitro expanded MSC, or of minimally manipulated MNC; moreover, the fourth group underwent sham operation. At day 30, histologic, morphometric, in-vitro contractility, and functional analysis were performed.<br><br>RESULTS: Treatment with both MSC and MNC improved muscle regeneration and increased contractile function of anal sphincters after SR compared with CTR (p < 0.05). No significant difference was observed between the two BM stem cell types used. GFP-positive cells (MSC and MNC) remained in the proximity of the lesion site up to 30 days post injection.<br><br>CONCLUSIONS: In the present study we demonstrated in a preclinical model that minimally manipulated BM-MNC were as effective as in-vitro expanded MSC for the recovery of anal sphincter injury followed by primary sphincter repair. These results may serve as a basis for improving clinical applications of stem cell therapy in human anal incontinence treatment.}, }
@article {pmid27327243, year = {2016}, author = {Wischmeyer, PE and McDonald, D and Knight, R}, title = {Role of the microbiome, probiotics, and 'dysbiosis therapy' in critical illness.}, journal = {Current opinion in critical care}, volume = {22}, number = {4}, pages = {347-353}, pmid = {27327243}, issn = {1531-7072}, mesh = {Critical Illness/*therapy ; Cross Infection ; Dysbiosis/*therapy ; Humans ; Intensive Care Units ; *Microbiota ; Probiotics/*therapeutic use ; }, abstract = {PURPOSE OF REVIEW: Loss of 'health-promoting' microbes and overgrowth of pathogenic bacteria (dysbiosis) in ICU is believed to contribute to nosocomial infections, sepsis, and organ failure (multiple organ dysfunction syndrome). This review discusses new understanding of ICU dysbiosis, new data for probiotics and fecal transplantation in ICU, and new data characterizing the ICU microbiome.<br><br>RECENT FINDINGS: ICU dysbiosis results from many factors, including ubiquitous antibiotic use and overuse. Despite advances in antibiotic therapy, infections and mortality from often multidrug-resistant organisms (i.e., Clostridium difficile) are increasing. This raises the question of whether restoration of a healthy microbiome via probiotics or other 'dysbiosis therapies' would be an optimal alternative, or parallel treatment option, to antibiotics. Recent clinical data demonstrate probiotics can reduce ICU infections and probiotics or fecal microbial transplant (FMT) can treat Clostridium difficile. This contributes to recommendations that probiotics should be considered to prevent infection in ICU. Unfortunately, significant clinical variability limits the strength of current recommendations and further large clinical trials of probiotics and FMT are needed. Before larger trials of 'dysbiosis therapy' can be thoughtfully undertaken, further characterization of ICU dysbiosis is needed. To addressing this, we conducted an initial analysis demonstrating a rapid and marked change from a 'healthy' microbiome to an often pathogen-dominant microbiota (dysbiosis) in a broad ICU population.<br><br>SUMMARY: A growing body of evidence suggests critical illness and ubiquitous antibiotic use leads to ICU dysbiosis that is associated with increased ICU infection, sepsis, and multiple organ dysfunction syndrome. Probiotics and FMT show promise as ICU therapies for infection. We hope future-targeted therapies using microbiome signatures can be developed to correct 'illness-promoting' dysbiosis to restore a healthy microbiome post-ICU to improve patient outcomes.}, }
@article {pmid27324973, year = {2016}, author = {Shimizu, H and Arai, K and Abe, J and Nakabayashi, K and Yoshioka, T and Hosoi, K and Kuroda, M}, title = {Repeated fecal microbiota transplantation in a child with ulcerative colitis.}, journal = {Pediatrics international : official journal of the Japan Pediatric Society}, volume = {58}, number = {8}, pages = {781-785}, doi = {10.1111/ped.12967}, pmid = {27324973}, issn = {1442-200X}, mesh = {Child ; Colitis, Ulcerative/diagnosis/microbiology/*therapy ; Colonoscopy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Humans ; Remission Induction ; }, abstract = {We report the case of an 11-year-old girl with ulcerative colitis refractory to conventional therapy, who was subsequently treated successfully with repeated fecal microbiota transplantation (FMT). The patient was steroid dependent despite several infliximab treatments, and colectomy was proposed to improve quality of life. After repeated FMT, she was able to maintain remission with on minimal dose of steroid. Although her fecal microbiota was dysbiotic before FMT, it was restored to a similar pattern as the donor after repeated FMT.}, }
@article {pmid27322054, year = {2016}, author = {Lei, YM and Chen, L and Wang, Y and Stefka, AT and Molinero, LL and Theriault, B and Aquino-Michaels, K and Sivan, AS and Nagler, CR and Gajewski, TF and Chong, AS and Bartman, C and Alegre, ML}, title = {The composition of the microbiota modulates allograft rejection.}, journal = {The Journal of clinical investigation}, volume = {126}, number = {7}, pages = {2736-2744}, pmid = {27322054}, issn = {1558-8238}, support = {T32 CA009594/CA/NCI NIH HHS/United States ; R01 AI071080/AI/NIAID NIH HHS/United States ; R01 AI115716/AI/NIAID NIH HHS/United States ; R01 AI106302/AI/NIAID NIH HHS/United States ; R01 AI072630/AI/NIAID NIH HHS/United States ; P01 AI097113/AI/NIAID NIH HHS/United States ; }, mesh = {Allografts ; Animals ; Anti-Bacterial Agents/therapeutic use ; Antigen-Presenting Cells ; Female ; Gene Expression Regulation ; *Graft Rejection ; Graft Survival/immunology ; Histocompatibility Antigens Class II/metabolism ; Leukocytes/cytology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; *Microbiota ; Organ Transplantation ; Skin/*microbiology ; *Skin Transplantation ; T-Lymphocytes/metabolism ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {Transplantation is the only cure for end-stage organ failure, but without immunosuppression, T cells rapidly reject allografts. While genetic disparities between donor and recipient are major determinants of the kinetics of transplant rejection, little is known about the contribution of environmental factors. Because colonized organs have worse transplant outcome than sterile organs, we tested the influence of host and donor microbiota on skin transplant rejection. Compared with untreated conventional mice, pretreatment of donors and recipients with broad-spectrum antibiotics (Abx) or use of germ-free (GF) donors and recipients resulted in prolonged survival of minor antigen-mismatched skin grafts. Increased graft survival correlated with reduced type I IFN signaling in antigen-presenting cells (APCs) and decreased priming of alloreactive T cells. Colonization of GF mice with fecal material from untreated conventional mice, but not from Abx-pretreated mice, enhanced the ability of APCs to prime alloreactive T cells and accelerated graft rejection, suggesting that alloimmunity is modulated by the composition of microbiota rather than the quantity of bacteria. Abx pretreatment of conventional mice also delayed rejection of major antigen-mismatched skin and MHC class II-mismatched cardiac allografts. This study demonstrates that Abx pretreatment prolongs graft survival, suggesting that targeting microbial constituents is a potential therapeutic strategy for enhancing graft acceptance.}, }
@article {pmid27319972, year = {2017}, author = {Dinan, TG and Cryan, JF}, title = {Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {42}, number = {1}, pages = {178-192}, pmid = {27319972}, issn = {1740-634X}, mesh = {Animals ; *Brain ; *Gastrointestinal Microbiome ; Humans ; *Immune System ; *Inflammation ; *Mental Disorders ; *Psychoneuroimmunology ; }, abstract = {There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated genomic structure. Bacteria within the gut are estimated to weigh in excess of 1 kg in the adult human and the microbes within not only produce antimicrobial peptides, short chain fatty acids, and vitamins, but also most of the common neurotransmitters found in the human brain. That the microbial content of the gut plays a key role in immune development is now beyond doubt. Early disruption of the host-microbe interplay can have lifelong consequences, not just in terms of intestinal function but in distal organs including the brain. It is clear that the immune system and nervous system are in continuous communication in order to maintain a state of homeostasis. Significant gaps in knowledge remain about the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. However, studies using germ-free animals, infective models, prebiotics, probiotics, and antibiotics have increased our understanding of the interplay. Early life stress can have a lifelong impact on the microbial content of the intestine and permanently alter immune functioning. That early life stress can also impact adult psychopathology has long been appreciated in psychiatry. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, immune, and central nervous systems in a network of communication that impacts behavior patterns and psychopathology, to eventually translate these findings to the human situation both in health and disease. Even at this juncture, there is evidence to pinpoint key sites of communication where gut microbial interventions either with drugs or diet or perhaps fecal microbiota transplantation may positively impact mental health.}, }
@article {pmid27317794, year = {2016}, author = {Jouhten, H and Mattila, E and Arkkila, P and Satokari, R}, title = {Reduction of Antibiotic Resistance Genes in Intestinal Microbiota of Patients With Recurrent Clostridium difficile Infection After Fecal Microbiota Transplantation.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {63}, number = {5}, pages = {710-711}, doi = {10.1093/cid/ciw390}, pmid = {27317794}, issn = {1537-6591}, mesh = {Anti-Bacterial Agents ; Clostridioides difficile ; Clostridium Infections ; Drug Resistance, Microbial ; *Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Microbiota ; }, }
@article {pmid27315076, year = {2016}, author = {Wonderlick, JS and D'Agostino, R}, title = {Fecal microbiota transplantation via fluoroscopy-guided nasojejunal catheter placement: indications, technique, and the role of radiology.}, journal = {Abdominal radiology (New York)}, volume = {41}, number = {10}, pages = {2020-2025}, doi = {10.1007/s00261-016-0801-0}, pmid = {27315076}, issn = {2366-0058}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; *Fluoroscopy ; Humans ; Intubation, Gastrointestinal/methods ; Male ; Patient Selection ; }, abstract = {Clostridium difficile is a well-established cause of nosocomial gastrointestinal disease. Although antibiotics remain an effective first-line treatment for C. difficile colitis (CDC), relapse and recurrence are common. FMT has emerged as one of the safest and most effective known therapies available for recurrent or refractory CDC, which is likely due to restoration of the protective microbiotic barrier of the gastrointestinal tract. FMT varies greatly across institutions by route of delivery, dose, and protocol. We present our experience with FMT via fluoroscopic-guided nasojejunal catheter placement. The discussion will include indications and contraindications, protocol, and procedural technique, and include a case presentation incorporating original CT and fluoroscopic images. Specifically, we will address the advantages and disadvantages of image-guided FMT via the upper GI tract with respect to nasogastric-, colonoscopic-, and enema-based delivery. The efficacy of FMT for the treatment of C. difficile has been widely demonstrated in several prospective and case studies. We feel that nasojejunal FMT is an underutilized radiologic procedure which can benefit selected patients, particularly given the advantages in risk profile, cost, convenience, and lack of routine sedation.}, }
@article {pmid27314511, year = {2016}, author = {Gloor, GB and Reid, G}, title = {Compositional analysis: a valid approach to analyze microbiome high-throughput sequencing data.}, journal = {Canadian journal of microbiology}, volume = {62}, number = {8}, pages = {692-703}, doi = {10.1139/cjm-2015-0821}, pmid = {27314511}, issn = {1480-3275}, mesh = {Canada ; Cluster Analysis ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; Probiotics ; Sequence Analysis, DNA ; }, abstract = {A workshop held at the 2015 annual meeting of the Canadian Society of Microbiologists highlighted compositional data analysis methods and the importance of exploratory data analysis for the analysis of microbiome data sets generated by high-throughput DNA sequencing. A summary of the content of that workshop, a review of new methods of analysis, and information on the importance of careful analyses are presented herein. The workshop focussed on explaining the rationale behind the use of compositional data analysis, and a demonstration of these methods for the examination of 2 microbiome data sets. A clear understanding of bioinformatics methodologies and the type of data being analyzed is essential, given the growing number of studies uncovering the critical role of the microbiome in health and disease and the need to understand alterations to its composition and function following intervention with fecal transplant, probiotics, diet, and pharmaceutical agents.}, }
@article {pmid27312892, year = {2016}, author = {Miller, AW and Oakeson, KF and Dale, C and Dearing, MD}, title = {Microbial Community Transplant Results in Increased and Long-Term Oxalate Degradation.}, journal = {Microbial ecology}, volume = {72}, number = {2}, pages = {470-478}, pmid = {27312892}, issn = {1432-184X}, support = {F32 DK102277/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria, Anaerobic/isolation &amp; purification/*metabolism ; Biomass ; Feces/chemistry/microbiology ; Female ; *Gastrointestinal Microbiome ; Male ; Oxalates/*metabolism ; Oxalobacter formigenes/isolation &amp; purification/*metabolism ; Probiotics ; Rats ; Rats, Sprague-Dawley ; Sigmodontinae/*microbiology ; }, abstract = {Gut microbes are essential for the degradation of dietary oxalate, and this function may play a role in decreasing the incidence of kidney stones. However, many oxalate-degrading bacteria are susceptible to antibiotics and the use of oxalate-degrading probiotics has only led to an ephemeral reduction in urinary oxalate. The objective of the current study was to determine the efficacy of using whole-community microbial transplants from a wild mammalian herbivore, Neotoma albigula, to increase oxalate degradation over the long term in the laboratory rat, Rattus norvegicus. We quantified the change in total oxalate degradation in lab rats immediately after microbial transplants and at 2- and 9-month intervals following microbial transplants. Additionally, we tracked the fecal microbiota of the lab rats, with and without microbial transplants, using high-throughput Illumina sequencing of a hyper-variable region of the 16S rRNA gene. Microbial transplants resulted in a significant increase in oxalate degradation, an effect that persisted 9 months after the initial transplants. Functional persistence was corroborated by the transfer, and persistence of a group of bacteria previously correlated with oxalate consumption in N. albigula, including an anaerobic bacterium from the genus Oxalobacter known for its ability to use oxalate as a sole carbon source. The results of this study indicate that whole-community microbial transplants are an effective means for the persistent colonization of oxalate-degrading bacteria in the mammalian gut.}, }
@article {pmid27312712, year = {2016}, author = {Kuperman, AA and Koren, O}, title = {Antibiotic use during pregnancy: how bad is it?.}, journal = {BMC medicine}, volume = {14}, number = {1}, pages = {91}, pmid = {27312712}, issn = {1741-7015}, mesh = {Anti-Bacterial Agents/*adverse effects/therapeutic use ; Dysbiosis/*chemically induced/diagnosis/drug therapy ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Microbiota/drug effects/physiology ; Pregnancy ; Pregnancy Complications, Infectious/diagnosis/drug therapy ; Prenatal Exposure Delayed Effects/*chemically induced/diagnosis/drug therapy ; Probiotics/therapeutic use ; }, abstract = {BACKGROUND: Our microbial companions (the "microbiota") are extremely important for the preservation of human health. Although changes in bacterial communities (dysbiosis) are commonly associated with disease, such changes have also been described in healthy pregnancies, where the microbiome plays an essential role in maternal and child health outcomes, including normal immune and metabolic function in later life. Nevertheless, this new understanding of the importance of the microbiome has not yet influenced contemporary clinical practice regarding antibiotic use during pregnancy.<br><br>DISCUSSION: Antibiotic treatment during pregnancy is widespread in Western countries, and accounts for 80&#xa0;% of prescribed medications in pregnancy. However, antibiotic treatment, while at times lifesaving, can also have detrimental consequences. A single course of antibiotics perturbs bacterial communities, with evidence that the microbial ecosystem does not return completely to baseline following treatment. Antibiotics in pregnancy should be used only when indicated, choosing those with the narrowest range possible. Bacteria are essential for normal human development and, while antibiotic treatment during pregnancy has an important role in controlling and preventing infections, it may have undesired effects regarding the maternal and fetoplacental microbiomes. We expect that microbiota manipulation in pregnancy, through the use of probiotics and fecal microbiota transplantation, will be the subject of increasing clinical interest.}, }
@article {pmid27311602, year = {2017}, author = {Gräs, S and Tolstrup, CK and Lose, G}, title = {Regenerative medicine provides alternative strategies for the treatment of anal incontinence.}, journal = {International urogynecology journal}, volume = {28}, number = {3}, pages = {341-350}, pmid = {27311602}, issn = {1433-3023}, mesh = {Anal Canal/*injuries/surgery ; Animals ; Dogs ; Electric Stimulation ; Fecal Incontinence/*therapy ; Female ; Humans ; Male ; Mesenchymal Stem Cell Transplantation/*methods ; Mice ; Muscle, Skeletal/pathology ; Rabbits ; Rats ; Regenerative Medicine/*methods ; Tissue Engineering ; }, abstract = {INTRODUCTION AND HYPOTHESIS: Anal incontinence is a common disorder but current treatment modalities are not ideal and the development of new treatments is needed. The aim of this review was to identify the existing knowledge of regenerative medicine strategies in the form of cellular therapies or bioengineering as a treatment for anal incontinence caused by anal sphincter defects.<br><br>METHODS: PubMed was searched for preclinical and clinical studies in English published from January 2005 to January 2016.<br><br>RESULTS: Animal studies have demonstrated that cellular therapy in the form of local injections of culture-expanded skeletal myogenic cells stimulates repair of both acute and 2&#xa0;-&#xa0;4-week-old anal sphincter injuries. The results from a small clinical trial with ten patients and a case report support the preclinical findings. Animal studies have also demonstrated that local injections of mesenchymal stem cells stimulate repair of sphincter injuries, and a complex bioengineering strategy for creation and implantation of an intrinsically innervated internal anal sphincter construct has been successfully developed in a series of animal studies.<br><br>CONCLUSION: Cellular therapies with myogenic cells and mesenchymal stem cells and the use of bioengineering technology to create an anal sphincter are new potential strategies to treat anal incontinence caused by anal sphincter defects, but the clinical evidence is extremely limited. The use of culture-expanded autologous skeletal myogenic cells has been most intensively investigated and several clinical trials were ongoing at the time of this report. The cost-effectiveness of such a therapy is an issue and muscle fragmentation is suggested as a simple alternative.}, }
@article {pmid27301272, year = {2016}, author = {Wang, H and Gao, K and Wen, K and Allen, IC and Li, G and Zhang, W and Kocher, J and Yang, X and Giri-Rachman, E and Li, GH and Clark-Deener, S and Yuan, L}, title = {Lactobacillus rhamnosus GG modulates innate signaling pathway and cytokine responses to rotavirus vaccine in intestinal mononuclear cells of gnotobiotic pigs transplanted with human gut microbiota.}, journal = {BMC microbiology}, volume = {16}, number = {1}, pages = {109}, pmid = {27301272}, issn = {1471-2180}, support = {R01 AT004789/AT/NCCIH NIH HHS/United States ; }, mesh = {Animals ; Biodiversity ; Cytokines/*immunology ; Disease Models, Animal ; Dose-Response Relationship, Immunologic ; Feces/microbiology ; Gastrointestinal Microbiome/*immunology ; Germ-Free Life/*immunology ; Humans ; Intestines/*immunology/microbiology/virology ; Lacticaseibacillus rhamnosus/*immunology ; Probiotics/administration &amp; dosage ; Rotavirus Infections/immunology/prevention &amp; control/virology ; Rotavirus Vaccines/*immunology/*pharmacology ; Signal Transduction/immunology ; Swine ; T-Lymphocytes/immunology ; Vaccines, Attenuated/immunology/pharmacology ; }, abstract = {BACKGROUND: A better understanding of mechanisms underlying dose-effects of probiotics in their applications as treatments of intestinal infectious or inflammatory diseases and as vaccine adjuvant is needed. In this study, we evaluated the modulatory effects of Lactobacillus rhamnosus GG (LGG) on transplanted human gut microbiota (HGM) and on small intestinal immune cell signaling pathways in gnotobiotic pigs vaccinated with an oral attenuated human rotavirus (AttHRV) vaccine.<br><br>RESULTS: Neonatal HGM transplanted pigs were given two doses of AttHRV on 5 and 15&#xa0;days of age and were divided into three groups: none-LGG (AttHRV), 9-doses LGG (AttHRV&#x2009;+&#x2009;LGG9X), and 14-doses LGG (AttHRV&#x2009;+&#x2009;LGG14X) (n&#x2009;=&#x2009;3-4). At post-AttHRV-inoculation day 28, all pigs were euthanized and intestinal contents and ileal tissue and mononuclear cells (MNC) were collected. AttHRV&#x2009;+&#x2009;LGG14X pigs had significantly increased LGG titers in the large intestinal contents and shifted structure of the microbiota as indicated by the formation of a cluster that is separated from the cluster formed by the AttHRV and AttHRV&#x2009;+&#x2009;LGG9X pigs. The increase in LGG titers concurred with significantly increased ileal HRV-specific IFN-&#x3b3; producing T cell responses to the AttHRV vaccine reported in our previous publication, suggesting pro-Th1 adjuvant effects of the LGG. Both 9- and 14-doses LGG fed pig groups had significantly higher IkB&#x3b1; level and p-p38/p38 ratio, while significantly lower p-ERK/ERK ratio than the AttHRV pigs, suggesting activation of regulatory signals during immune activation. However, 9-doses, but not 14-doses LGG fed pigs had enhanced IL-6, IL-10, TNF-&#x3b1;, TLR9 mRNA levels, and p38 MAPK and ERK expressions in ileal MNC. Increased TLR9 mRNA was in parallel with higher mRNA levels of cytokines, p-NF-kB and higher p-p38/p38 ratio in MNC of the AttHRV&#x2009;+&#x2009;LGG9X pigs.<br><br>CONCLUSIONS: The relationship between modulation of gut microbiota and regulation of host immunity by different doses of probiotics is complex. LGG exerted divergent dose-dependent effects on the intestinal immune cell signaling pathway responses, with 9-doses LGG being more effective in activating the innate immunostimulating TLR9 signaling pathway than 14-doses in the HGM pigs vaccinated with AttHRV.}, }
@article {pmid27301110, year = {2016}, author = {Tkachenko, EI and Sitkin, SI and Oreshko, LS and Medvedeva, OI}, title = {[TROPHOLOGY ASPECTS OF NOOCPHEROGENESIS. On the 90th anniversary of A M Ugolev].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental &amp; clinical gastroenterology}, volume = {}, number = {2}, pages = {4-13}, pmid = {27301110}, issn = {1682-8658}, mesh = {*Biomedical Research ; Digestion/physiology ; *Digestive System Diseases/etiology/metabolism/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; *Nutritional Physiological Phenomena ; }, abstract = {This paper presents an analytical review of A. Ugolev's scientific heritage (the theory of adequate nutrition, all-purpose functional blocks, the unity of natural and artificial technologies, the discovery of membrane digestion, new doctrine--trophology) to explain trophological aspects of noospherogenesis. The authors have presented their specific views for the development of these ideas; the theory of therapeutic infections, the holistic theory of nutrition, the endoecological deficiency syndrome, the activation of all-purpose functional blocks, evasion receptors, new principles of treatment with the effects on microbiota, combining the essence of the diseases and their treatment.}, }
@article {pmid27296387, year = {2016}, author = {Luvira, V and Trakulhun, K and Mungthin, M and Naaglor, T and Chantawat, N and Pakdee, W and Phiboonbanakit, D and Dekumyoy, P}, title = {Comparative Diagnosis of Strongyloidiasis in Immunocompromised Patients.}, journal = {The American journal of tropical medicine and hygiene}, volume = {95}, number = {2}, pages = {401-404}, pmid = {27296387}, issn = {1476-1645}, mesh = {Adult ; Aged ; Animals ; Antibodies, Helminth/*blood ; Cross-Sectional Studies ; Enzyme-Linked Immunosorbent Assay ; Feces/parasitology ; Female ; Humans ; *Immunocompromised Host ; Immunoglobulin G/*blood ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Sensitivity and Specificity ; Strongyloides stercoralis/*immunology/isolation &amp; purification ; Strongyloidiasis/*diagnosis/*epidemiology/immunology/parasitology ; Thailand/epidemiology ; }, abstract = {Strongyloides hyperinfection syndrome and disseminated strongyloidiasis frequently occur in immunocompromised persons and can lead to high complication and mortality rates. Thus, detection of Strongyloides stercolaris in those patients is crucial. The present study aimed to determine the prevalence of strongyloidiasis and compare the detection rates of different strongyloidiasis detection methods. We conducted a cross-sectional study of 135 adults with various immunocompromising conditions (corticosteroid usage, chemotherapy, hematologic malignancies, organ transplants, use of immunosuppressive agents, and symptomatic human immunodeficiency virus infection) in Phramongkutklao Hospital, Bangkok, Thailand. All patients were asked to undergo serology testing for Strongyloides IgG by indirect enzyme-linked immunosorbent assay (ELISA), and 3 days of stool collection for use in a simple smear along with formalin-ether concentration and agar plate techniques. Prevalence rates of strongyloidiasis were 5% by stool concentration technique, 5.4% by IgG-ELISA, and 6.7% by agar plate culture. Three of the eight strongyloidiasis cases in this study had hyperinfection syndrome. The tested risk factors of age, sex, occupation, and immunocompromising condition were not associated with Strongyloides infestation. Serology was only 42.9% sensitive (positive predictive value), but it was 96.3% specific (negative predictive value). In conclusion, prevalence rates of strongyloidiasis in this study were 5-7%. Although agar plate culture was the most sensitive technique, the other diagnostic methods might be alternatively used.}, }
@article {pmid27295210, year = {2016}, author = {Shi, Y and Dong, Y and Huang, W and Zhu, D and Mao, H and Su, P}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis.}, journal = {PloS one}, volume = {11}, number = {6}, pages = {e0157259}, pmid = {27295210}, issn = {1932-6203}, mesh = {Colitis, Ulcerative/*microbiology/*therapy ; Fecal Microbiota Transplantation/*adverse effects/*methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear.<br><br>OBJECTIVE: We conducted this systematic review to assess the efficacy and safety of FMT in UC.<br><br>DATA SOURCES: PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes.<br><br>DATA EXTRACTION AND SYNTHESIS: We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies.<br><br>RESULTS: Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition.<br><br>CONCLUSION: FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.}, }
@article {pmid27291426, year = {2016}, author = {Lee, J and Choi, JH and Kim, HJ}, title = {Human gut-on-a-chip technology: will this revolutionize our understanding of IBD and future treatments?.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {10}, number = {8}, pages = {883-885}, doi = {10.1080/17474124.2016.1200466}, pmid = {27291426}, issn = {1747-4132}, mesh = {Biomimetic Materials ; Diffusion of Innovation ; Gastrointestinal Microbiome ; *Gastrointestinal Tract/microbiology/physiopathology ; Humans ; Inflammatory Bowel Diseases/microbiology/physiopathology/*therapy ; *Lab-On-A-Chip Devices ; *Microchip Analytical Procedures ; Micromanipulation ; Translational Research, Biomedical ; }, }
@article {pmid27286042, year = {2016}, author = {Broecker, F and Klumpp, J and Moelling, K}, title = {Long-term microbiota and virome in a Zürich patient after fecal transplantation against Clostridium difficile infection.}, journal = {Annals of the New York Academy of Sciences}, volume = {1372}, number = {1}, pages = {29-41}, doi = {10.1111/nyas.13100}, pmid = {27286042}, issn = {1749-6632}, mesh = {Clostridioides difficile/*physiology ; Clostridium Infections/*microbiology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Middle Aged ; Switzerland ; Time Factors ; Viruses/*metabolism ; }, abstract = {Fecal microbiota transplantation (FMT) is an emerging therapeutic option for Clostridium difficile infections that are refractory to conventional treatment. FMT introduces fecal microbes into the patient's intestine that prevent the recurrence of C. difficile, leading to rapid expansion of bacteria characteristic of healthy microbiota. However, the long-term effects of FMT remain largely unknown. The C. difficile patient described in this paper revealed protracted microbiota adaptation processes from 6 to 42 months post-FMT. Ultimately, bacterial communities were donor similar, suggesting sustainable stool engraftment. Since little is known about the consequences of transmitted viruses during C. difficile infection, we also interrogated virome changes. Our approach allowed identification of about 10 phage types per sample that represented larger viral communities, and phages were found to be equally abundant in the cured patient and donor. The healthy microbiota appears to be characterized by low phage abundance. Although viruses were likely transferred, the patient established a virome distinct from the donor. Surprisingly, the patient had sequences of algal giant viruses (chloroviruses) that have not previously been reported for the human gut. Chloroviruses have not been associated with intestinal disease, but their presence in the oropharynx may influence cognitive abilities. The findings suggest that the virome is an important indicator of health or disease. A better understanding of the role of viruses in the gut ecosystem may uncover novel microbiota-modulating therapeutic strategies.}, }
@article {pmid27284173, year = {2016}, author = {Amirtha, T}, title = {MICROBIOME RESEARCH. Banking on stool despite an uncertain future.}, journal = {Science (New York, N.Y.)}, volume = {352}, number = {6291}, pages = {1261-1262}, doi = {10.1126/science.352.6291.1261}, pmid = {27284173}, issn = {1095-9203}, mesh = {*Biological Specimen Banks ; Clostridioides difficile ; Enterocolitis, Pseudomembranous/prevention &amp; control ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Netherlands ; Recurrence ; Uncertainty ; }, }
@article {pmid27283939, year = {2016}, author = {Bolan, S and Seshadri, B and Talley, NJ and Naidu, R}, title = {Bio-banking gut microbiome samples.}, journal = {EMBO reports}, volume = {17}, number = {7}, pages = {929-930}, pmid = {27283939}, issn = {1469-3178}, mesh = {Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Tissue Banks ; }, abstract = {An increasing number of academic and private biobanks store faecal samples for research and stool transplantation purposes. As stool samples are unique from other biological tissues and materials, stool biobanks require appropriate regulation and additional research on gut microbiota to ensure safe application in the clinic. [Image: see text]}, }
@article {pmid27281075, year = {2016}, author = {Sun, D and Li, W and Li, S and Cen, Y and Xu, Q and Li, Y and Sun, Y and Qi, Y and Lin, Y and Yang, T and Xu, P and Lu, Q}, title = {Fecal Microbiota Transplantation as a Novel Therapy for Ulcerative Colitis: A Systematic Review and Meta-Analysis.}, journal = {Medicine}, volume = {95}, number = {23}, pages = {e3765}, pmid = {27281075}, issn = {1536-5964}, mesh = {Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Microbiota ; Remission Induction ; }, abstract = {Variation in clinical evidence has prevented the adoption of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). We aimed to conduct a systematic review and meta-analysis to determine the efficacy and safety of FMT in UC.A systematic literature search was performed in 5 electronic databases from inception through September 2015. Inclusion criteria were reports of FMT in patients with UC. Studies were excluded if they did not report clinical outcomes or included patients with infections. Clinical remission (CR) was defined as the primary outcome.Eleven studies (2 randomized controlled trials (RCTs), 1 open-label case-control study, and 8 cohort studies) with a total of 133 UC patients were included in the analysis. In 11 studies (including 8 noncontrol cohort studies and the treatment arms of 3 clinical control trials), the pooled proportion of patients who achieved CR was 30.4% (95% CI 22.6-39.4%), with a low risk of heterogeneity (Cochran Q test, P = 0.139; I = 33%). A subgroup analysis suggested that no difference in CR was detected between upper gastrointestinal delivery versus lower gastrointestinal delivery. Furthermore, subgroup analysis revealed that there was no difference in CR between single infusion versus multiple infusions (>1) of FMT. All studies reported mild adverse events.FMT is potentially useful in UC disease management but better-designed RCTs are still required to confirm our findings before wide adoption of FMT is suggested. Additionally, basic guidelines are needed imminently to identify the right patient population and to standardize the process of FMT.}, }
@article {pmid27279225, year = {2016}, author = {Planer, JD and Peng, Y and Kau, AL and Blanton, LV and Ndao, IM and Tarr, PI and Warner, BB and Gordon, JI}, title = {Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice.}, journal = {Nature}, volume = {534}, number = {7606}, pages = {263-266}, pmid = {27279225}, issn = {1476-4687}, support = {GM007200/GM/NIGMS NIH HHS/United States ; R01 DK030292/DK/NIDDK NIH HHS/United States ; DK052574/DK/NIDDK NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; DK30292/DK/NIDDK NIH HHS/United States ; T32 GM007067/GM/NIGMS NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; K08 AI113184/AI/NIAID NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; }, mesh = {Aging/*immunology ; Animals ; Breast Feeding ; Child, Preschool ; Diet ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; *Germ-Free Life ; Healthy Volunteers ; Humans ; Immunity, Mucosal/*immunology ; Immunoglobulin A/*immunology ; Infant ; Intestines/immunology/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; *Models, Animal ; *Twins ; Weaning ; }, abstract = {Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function. The repertoire of IgA bound to gut bacteria reflects both T-cell-dependent and -independent pathways, plus glycans present on the antibody's secretory component. Human gut bacterial taxa targeted by IgA in the setting of barrier dysfunction are capable of producing intestinal pathology when isolated and transferred to gnotobiotic mice. A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA. How IgA responses co-develop with assembly of the microbiota during this period remains poorly understood. Here, we (1) identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly and maturation during the first 2 postnatal years that is shared across 40 healthy twin pairs in the USA; (2) describe a pattern of progression of gut mucosal IgA responses to bacterial members of the microbiota that is highly distinctive for family members (twin pairs) during the first several postnatal months then generalizes across pairs in the second year; and (3) assess the effects of zygosity, birth mode, and breast feeding. Age-associated differences in these IgA responses can be recapitulated in young germ-free mice, colonized with faecal microbiota obtained from two twin pairs at 6 and 18 months of age, and fed a sequence of human diets that simulate the transition from milk feeding to complementary foods. Most of these responses were robust to diet, suggesting that 'intrinsic' properties of community members play a dominant role in dictating IgA responses. The approach described can be used to define gut mucosal immune development in health and disease states and to help discover ways of repairing or preventing perturbations in this facet of host immunity.}, }
@article {pmid27279224, year = {2016}, author = {Bashan, A and Gibson, TE and Friedman, J and Carey, VJ and Weiss, ST and Hohmann, EL and Liu, YY}, title = {Universality of human microbial dynamics.}, journal = {Nature}, volume = {534}, number = {7606}, pages = {259-262}, pmid = {27279224}, issn = {1476-4687}, support = {R01 HL091528/HL/NHLBI NIH HHS/United States ; }, mesh = {Clostridioides difficile/physiology ; Clostridium Infections/microbiology ; Computer Simulation ; Cross-Sectional Studies ; Datasets as Topic ; *Ecosystem ; Environment ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Healthy Volunteers ; Humans ; Intestines/microbiology ; Metagenomics ; Microbiota/*physiology ; Mouth/microbiology ; Organ Specificity ; Skin/microbiology ; Species Specificity ; }, abstract = {Human-associated microbial communities have a crucial role in determining our health and well-being, and this has led to the continuing development of microbiome-based therapies such as faecal microbiota transplantation. These microbial communities are very complex, dynamic and highly personalized ecosystems, exhibiting a high degree of inter-individual variability in both species assemblages and abundance profiles. It is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra- and inter-species interactions in population dynamics models, are largely host-independent (that is, universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle, physiology or genetics, then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species. Here we develop a new computational method to characterize human microbial dynamics. By applying this method to cross-sectional data from two large-scale metagenomic studies--the Human Microbiome Project and the Student Microbiome Project--we show that gut and mouth microbiomes display pronounced universal dynamics, whereas communities associated with certain skin sites are probably shaped by differences in the host environment. Notably, the universality of gut microbial dynamics is not observed in subjects with recurrent Clostridium difficile infection but is observed in the same set of subjects after faecal microbiota transplantation. These results fundamentally improve our understanding of the processes that shape human microbial ecosystems, and pave the way to designing general microbiome-based therapies.}, }
@article {pmid27279212, year = {2016}, author = {Stappenbeck, TS and Virgin, HW}, title = {Accounting for reciprocal host-microbiome interactions in experimental science.}, journal = {Nature}, volume = {534}, number = {7606}, pages = {191-199}, pmid = {27279212}, issn = {1476-4687}, mesh = {Animals ; Biomedical Research/*methods/*standards ; Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Metagenome/*genetics ; Mice ; Microbiota/*genetics ; Models, Animal ; Phenotype ; Reference Standards ; Reproducibility of Results ; *Research Design ; Sequence Analysis, DNA ; }, abstract = {Mammals are defined by their metagenome, a combination of host and microbiome genes. This knowledge presents opportunities to further basic biology with translation to human diseases. However, the now-documented influence of the metagenome on experimental results and the reproducibility of in vivo mammalian models present new challenges. Here we provide the scientific basis for calling on all investigators, editors and funding agencies to embrace changes that will enhance reproducible and interpretable experiments by accounting for metagenomic effects. Implementation of new reporting and experimental design principles will improve experimental work, speed discovery and translation, and properly use substantial investments in biomedical research.}, }
@article {pmid27256713, year = {2016}, author = {Abdollahi-Roodsaz, S and Abramson, SB and Scher, JU}, title = {The metabolic role of the gut microbiota in health and rheumatic disease: mechanisms and interventions.}, journal = {Nature reviews. Rheumatology}, volume = {12}, number = {8}, pages = {446-455}, pmid = {27256713}, issn = {1759-4804}, support = {R03 AR072182/AR/NIAMS NIH HHS/United States ; K23 AR064318/AR/NIAMS NIH HHS/United States ; RC2 AR058986/AR/NIAMS NIH HHS/United States ; }, mesh = {Antirheumatic Agents/metabolism ; Bile Acids and Salts/metabolism ; Diet ; Fatty Acids, Volatile/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Prebiotics ; Probiotics ; Rheumatic Diseases/drug therapy/*metabolism/*microbiology ; }, abstract = {The role of the gut microbiome in animal models of inflammatory and autoimmune disease is now well established. The human gut microbiome is currently being studied as a potential modulator of the immune response in rheumatic disorders. However, the vastness and complexity of this host-microorganism interaction is likely to go well beyond taxonomic, correlative observations. In fact, most advances in the field relate to the functional and metabolic capabilities of these microorganisms and their influence on mucosal immunity and systemic inflammation. An intricate relationship between the microbiome and the diet of the host is now fully recognized, with the microbiota having an important role in the degradation of polysaccharides into active metabolites. This Review summarizes the current knowledge on the metabolic role of the microbiota in health and rheumatic disease, including the advances in pharmacomicrobiomics and its potential use in diagnostics, therapeutics and personalized medicine.}, }
@article {pmid27255389, year = {2016}, author = {John, GK and Mullin, GE}, title = {The Gut Microbiome and Obesity.}, journal = {Current oncology reports}, volume = {18}, number = {7}, pages = {45}, pmid = {27255389}, issn = {1534-6269}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; Obesity/microbiology/*physiopathology/prevention &amp; control ; Probiotics/therapeutic use ; }, abstract = {The gut microbiome consists of trillions of bacteria which play an important role in human metabolism. Animal and human studies have implicated distortion of the normal microbial balance in obesity and metabolic syndrome. Bacteria causing weight gain are thought to induce the expression of genes related to lipid and carbohydrate metabolism thereby leading to greater energy harvest from the diet. There is a large body of evidence demonstrating that alteration in the proportion of Bacteroidetes and Firmicutes leads to the development of obesity, but this has been recently challenged. It is likely that the influence of gut microbiome on obesity is much more complex than simply an imbalance in the proportion of these phyla of bacteria. Modulation of the gut microbiome through diet, pre- and probiotics, antibiotics, surgery, and fecal transplantation has the potential to majorly impact the obesity epidemic.}, }
@article {pmid27250592, year = {2016}, author = {Gundacker, ND and Morrow, CD and Rodriguez, M}, title = {Letter: a simple out-patient faecal microbiota transplant technique.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {44}, number = {1}, pages = {101}, doi = {10.1111/apt.13648}, pmid = {27250592}, issn = {1365-2036}, support = {P30 CA013148/CA/NCI NIH HHS/United States ; }, }
@article {pmid27246640, year = {2016}, author = {Beneš, J and Polívková, S}, title = {[Antibiotic treatment of clostridial colitis].}, journal = {Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne}, volume = {65}, number = {1}, pages = {15-24}, pmid = {27246640}, issn = {1210-7913}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile ; Drug Resistance, Bacterial ; Enterocolitis, Pseudomembranous/*drug therapy ; Fidaxomicin ; Humans ; Metronidazole/therapeutic use ; Recurrence ; Vancomycin/therapeutic use ; }, abstract = {The advantages and disadvantages of various antibiotics used in the treatment of Clostridium difficile infection (CDI) are compared with respect to their pharmacokinetic and pharmacodynamic properties. Recommendations are made for their optimal use in clinical practice. Metronidazole is suitable for the treatment of mild forms of CDI which are essentially self-limiting. Vancomycin kills clostridia reliably but the treatment is encumbered with considerable risk of recurrence. This can be decreased by shortening the treatment to seven days and then switching to a (pulse, taper, chaser) regimen to prevent recurrence or by active restoration of the intestinal ecosystem (fecal transplant). Fidaxomicin works faster than vancomycin and is associated with a lower risk of recurrence. Thus, it can be profitably used in patients with impending ileus and also in those whose medical condition does not allow prolonged treatment. The duration of fidaxomicin treatment could be reduced to as few as five days. Rifaximin does not have a clear place in the treatment of CDI because no compelling data are available on its efficacy in this disease. The risk of resistance is also important. Tigecycline is a promising antibiotic for parenteral use. According to the available data, it should be more effective than intravenous metronidazole which has been considered the drug of choice.Clostridial colitis is associated with intestinal dysmicrobia which is the major cause of recurrence. Severe dysmicrobia cannot be treated by antibiotics but only by gut flora restoration; stool transplant from a healthy donor is the only proven therapy for this condition.}, }
@article {pmid27239328, year = {2016}, author = {Sbahi, H and Di Palma, JA}, title = {Faecal microbiota transplantation: applications and limitations in treating gastrointestinal disorders.}, journal = {BMJ open gastroenterology}, volume = {3}, number = {1}, pages = {e000087}, pmid = {27239328}, issn = {2054-4774}, abstract = {The process of stool transfer from healthy donors to the sick, known as faecal microbiota transplantation (FMT), has an ancient history. However, only recently researchers started investigating its applications in an evidence-based manner. Current knowledge of the microbiome, the concept of dysbiosis and results of preliminary research suggest that there is an association between gastrointestinal bacterial disruption and certain disorders. Researchers have studied the effects of FMT on various gastrointestinal and non-gastrointestinal diseases, but have been unable to precisely pinpoint specific bacterial strains responsible for the observed clinical improvement or futility of the process. The strongest available data support the efficacy of FMT in the treatment of recurrent Clostridium difficile infection with cure rates reported as high as 90% in clinical trials. The use of FMT in other conditions including inflammatory bowel disease, functional gastrointestinal disorders, obesity and metabolic syndrome is still controversial. Results from clinical studies are conflicting, which reflects the gap in our knowledge of the microbiome composition and function, and highlights the need for a more defined and personalised microbial isolation and transfer.}, }
@article {pmid27233894, year = {2016}, author = {Berro, ZZ and Hamdan, RH and Dandache, IH and Saab, MN and Karnib, HH and Younes, MH}, title = {Fecal microbiota transplantation for severe clostridium difficile infection after left ventricular assist device implantation: a case control study and concise review on the local and regional therapies.}, journal = {BMC infectious diseases}, volume = {16}, number = {}, pages = {234}, pmid = {27233894}, issn = {1471-2334}, mesh = {Aged ; Case-Control Studies ; *Clostridioides difficile/growth &amp; development ; Clostridium Infections/microbiology/*therapy ; Diarrhea/microbiology/therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Hemorrhage/microbiology/therapy ; Heart-Assist Devices/adverse effects/*microbiology ; Humans ; Lebanon ; Male ; Prosthesis Implantation/*adverse effects ; Prosthesis-Related Infections/microbiology/therapy ; }, abstract = {BACKGROUND: We report herein a case of fecal microbiota transplantation (FMT) used for severe Clostridium difficile infection for a 65-year-old Lebanese man who underwent left ventricular assist device implantation. To the best of our knowledge this is the first case report from Lebanon and the region presenting such technique.<br><br>CASE PRESENTATION: The patient experienced diarrhea and rectal bleeding and was diagnosed of pseudomembranous colitis (PMC). His condition failed to improve on maximal pharmacological therapy. Protocolectomy, an invasive operation consisting in resection of the entire colon and rectum seemed to be the last resort before the patient responded to FMT given through gastroscopy.<br><br>CONCLUSION: Despite the increasing experience with FMT for C. difficile infection, published evidence in severe related cases from this region is very limited. Hence, we promote adjunctive FMT, an effective noninvasive method, to be considered as a promising early treatment option in severe C. difficile infection.}, }
@article {pmid27221557, year = {2016}, author = {Ramsauer, B and König, C and Sabelhaus, T and Ockenga, J and Otte, JM}, title = {[Fecal microbiota transplantation in relapsing clostridium difficile colitis].}, journal = {MMW Fortschritte der Medizin}, volume = {158 Suppl 4}, number = {}, pages = {17-20}, doi = {10.1007/s15006-016-8305-y}, pmid = {27221557}, issn = {1438-3276}, mesh = {Aged ; Aged, 80 and over ; *Clostridioides difficile ; Colonoscopy ; Conscious Sedation ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Retreatment ; Retrospective Studies ; }, abstract = {BACKGROUND: Since the turn of the millennium there has been an alarming increase in the incidence and severity of clostridium difficile infections. Stopping medication with the triggering antibiotic and switching to a recommended antibiotic leads to healing up in 80%. However, patients who relapse have a 40% risk of an additional relapse and those with 2 or more episodes face a 60% risk. Fecal microbiota transplantation (FMT) is a new therapeutic option. Up to now there only exist two randomized studies (University of Amsterdam and the Massachusetts General Hospital in Boston).<br><br>METHOD: Data from 16 patients with recurrent clostridium difficile infection who had undergone FMT at a local hospital in the city of Bremen, Germany, were reviewed and compared to the results of the 2 randomized studies.<br><br>RESULTS: 11 out of 16 patients got cured after the first FMT (68.75%). The remaining 5 patients received a second FMT, with cure in 3 patients. The overall response rate was 14 from 16 patients (87.5%).<br><br>CONCLUSIONS: In comparison to the response rates of the University of Amsterdam (81.3% after the first and 93.8% after the second FMT) and of the Massachusetts General Hospital in Boston (70% after the first and 90% after the second FMT) we received slightly worse results. But, treatment of notably older patients and intensive care patients in our group explain these findings well. Therefore, we advocate a wide use of FMT for the treatment of recurrent clostridium difficile colitis in non-university hospitals.}, }
@article {pmid27220087, year = {2016}, author = {Yadav, V and Varum, F and Bravo, R and Furrer, E and Bojic, D and Basit, AW}, title = {Inflammatory bowel disease: exploring gut pathophysiology for novel therapeutic targets.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {176}, number = {}, pages = {38-68}, doi = {10.1016/j.trsl.2016.04.009}, pmid = {27220087}, issn = {1878-1810}, mesh = {Animals ; Biological Products/pharmacology/therapeutic use ; Gastrointestinal Tract/drug effects/microbiology/pathology/*physiopathology ; Humans ; Inflammatory Bowel Diseases/drug therapy/genetics/*physiopathology/*therapy ; Microbiota/drug effects ; *Molecular Targeted Therapy ; Signal Transduction/drug effects ; }, abstract = {Ulcerative colitis and Crohn's disease are the 2 major phenotypes of inflammatory bowel disease (IBD), which are influenced by a complex interplay of immunological and genetic elements, though the precise etiology still remains unknown. With IBD developing into a globally prevailing disease, there is a need to explore new targets and a thorough understanding of the pathophysiological differences between the healthy and diseased gut could unearth new therapeutic opportunities. In this review, we provide an overview of the major aspects of IBD pathogenesis and thereafter present a comprehensive analysis of the gut pathophysiology leading to a discussion on some of the most promising targets and biologic therapies currently being explored. These include various gut proteins (CXCL-10, GATA-3, NKG2D, CD98, microRNAs), immune cells recruited to the gut (mast cells, eosinophils, toll-like receptors 2, 4), dysregulated proinflammatory cytokines (interleukin-6, -13, -18, -21), and commensal microbiota (probiotics and fecal microbiota transplantation). We also evaluate some of the emerging nonconventional therapies being explored in IBD treatment focusing on the latest developments in stem cell research, oral targeting of the gut-associated lymphoid tissue, novel anti-inflammatory signaling pathway targeting, adenosine deaminase inhibition, and the beneficial effects of antioxidant and nutraceutical therapies. In addition, we highlight the growth of biologics and their targets in IBD by providing information on the preclinical and clinical development of over 60 biopharmaceuticals representing the state of the art in ulcerative colitis and Crohn's disease drug development.}, }
@article {pmid27217707, year = {2016}, author = {Ren, RR and Sun, G and Yang, YS and Peng, LH and Wang, SF and Shi, XH and Zhao, JQ and Ban, YL and Pan, F and Wang, XH and Lu, W and Ren, JL and Song, Y and Wang, JB and Lu, QM and Bai, WY and Wu, XP and Wang, ZK and Zhang, XM and Chen, Y}, title = {Chinese physicians' perceptions of fecal microbiota transplantation.}, journal = {World journal of gastroenterology}, volume = {22}, number = {19}, pages = {4757-4765}, pmid = {27217707}, issn = {2219-2840}, support = {F31 AA020702/AA/NIAAA NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; *Attitude of Health Personnel ; Awareness ; China ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Diseases/diagnosis/microbiology/*therapy ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; *Perception ; Physicians/*psychology ; Specialization ; Surveys and Questionnaires ; Young Adult ; }, abstract = {AIM: To explore Chinese physicians' perceptions towards fecal microbiota transplantation (FMT) and to provide information and an assessment of FMT development in China.<br><br>METHODS: A self-administered questionnaire was developed according to the FMT practice guidelines and was distributed to physicians in hospitals via Internet Research Electronic Data Capture (REDcap) software and electronic mails to assess their attitudes toward and knowledge of FMT. The questionnaire included a brief introduction of FMT that was followed by 20 questions. The participants were required to respond voluntarily, under the condition of anonymity and without compensation. Except for the fill-in-the-blank questions, all of the other questions were required in the REDcap data collection systems, and the emailed questionnaires were completed based on eligibility.<br><br>RESULTS: Up to December 9, 2014, 844 eligible questionnaires were received out of the 980 distributed questionnaires, with a response rate of 86.1%. Among the participants, 87.3% were from tertiary hospitals, and there were 647 (76.7%) gastroenterologists and 197 (23.3%) physicians in other departments (non-gastroenterologists). Gastroenterologists' awareness of FMT prior to the survey was much higher than non-gastroenterologists' (54.3 vs 16.5%, P < 0.001); however, acceptance of FMT was not statistically different (92.4 vs 87.1%, P = 0.1603). Major concerns of FMT included the following: acceptability to patients (79.2%), absence of guidelines (56.9%), and administration and ethics (46.5%). On the basis of understanding, the FMT indications preferred by physicians were recurrent Clostridium difficile infection (86.7%), inflammatory bowel disease combined with Clostridium difficile infection (78.6%), refractory ulcerative colitis (70.9%), ulcerative colitis (65.4%), Crohn's disease (59.4%), chronic constipation (43.7%), irritable bowel syndrome (39.1%), obesity (28.1%) and type 2 diabetes (23.9%). For donor selection, the majority of physicians preferred individuals with a similar gut flora environment to the recipients. 76.6% of physicians chose lower gastrointestinal tract as the administration approach. 69.2% of physicians considered FMT a safe treatment.<br><br>CONCLUSION: Chinese physicians have awareness and a high acceptance of FMT, especially gastroenterologists, which provides the grounds and conditions for the development of this novel treatment in China. Physicians' greatest concerns were patient acceptability and absence of guidelines.}, }
@article {pmid27214585, year = {2016}, author = {Webb, BJ and Brunner, A and Ford, CD and Gazdik, MA and Petersen, FB and Hoda, D}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {18}, number = {4}, pages = {628-633}, doi = {10.1111/tid.12550}, pmid = {27214585}, issn = {1399-3062}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Diarrhea/microbiology/*therapy ; Dysbiosis/complications/*therapy ; *Fecal Microbiota Transplantation/adverse effects/methods/mortality ; Feces/chemistry/microbiology ; Female ; Gastrointestinal Microbiome/immunology ; Graft vs Host Disease/drug therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunocompromised Host/immunology ; Immunosuppression Therapy/*adverse effects/methods ; Intestines/microbiology ; Male ; Middle Aged ; Treatment Outcome ; }, abstract = {Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor-derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25-75 interquartile range [IQR] 38-791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long-term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso-jejunal route in 6 of the 7 patients. Mean follow-up was 265 days (IQR 51-288). Minor post-FMT adverse effects included self-limited bloating and urgency. One patient was suspected of having post-FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all-cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft-versus-host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects.}, }
@article {pmid27213584, year = {2016}, author = {Brenner, H and Jansen, L and Ulrich, A and Chang-Claude, J and Hoffmeister, M}, title = {Survival of patients with symptom- and screening-detected colorectal cancer.}, journal = {Oncotarget}, volume = {7}, number = {28}, pages = {44695-44704}, pmid = {27213584}, issn = {1949-2553}, mesh = {Aged ; Cohort Studies ; Colonoscopy ; Colorectal Neoplasms/*diagnosis/mortality ; Early Detection of Cancer/*methods/statistics &amp; numerical data ; Female ; Germany ; Humans ; Male ; Mass Screening/*methods/statistics &amp; numerical data ; Middle Aged ; Multivariate Analysis ; Occult Blood ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Survival Rate ; }, abstract = {BACKGROUND: An increasing proportion of colorectal cancer (CRC) patients are diagnosed by screening rather than symptoms.<br><br>AIMS: We aimed to assess and compare prognosis of patients with screen-detected CRC and symptom-detected CRC.<br><br>METHODS: Overall and CRC specific mortality over a median follow-up of 4.8 years was assessed according to mode of diagnosis (symptoms, screening colonoscopy, fecal occult blood test [FOBT], other) in a multi-center cohort of 2,450 CRC patients aged 50-79 years recruited in Germany in 2003-2010.<br><br>RESULTS: 68%, 11% and 10% were detected by symptoms, screening colonoscopy and FOBT, respectively. The screen-detected cancers had a more favorable stage distribution than the symptom-detected cancers (68% versus 50% in stage I or II). Age- and sex adjusted hazard ratios (HRs) of total mortality with 95% confidence intervals (95% CIs) compared to symptom-detected cancers were 0.35 (0.24-0.50) and 0.36 (0.25-0.53) for screening colonoscopy and FOBT detected CRCs, respectively. HRs were only slightly attenuated and remained highly significant after adjustment for stage and multiple other covariates (0.50 (0.34-0.73) and 0.54 (0.37-0.80), respectively). Even stronger associations were seen for CRC specific mortality. Patients with screen-detected stage III CRC had as good CRC specific survival as patients with symptom-detected stage I or II CRC.<br><br>CONCLUSIONS: Patients with screen-detected CRC have a very good prognosis far beyond the level explained by their more favorable stage distribution. Mode of detection is an important, easy-to-obtain proxy indicator for favorable diagnosis beyond earlier stage at diagnosis and as such may be useful for risk stratification in treatment decisions.}, }
@article {pmid27213252, year = {2016}, author = {Romaniszyn, M and Wałęga, P}, title = {Graciloplasty, electrostimulation, electromyography. Clinical implications of electrophysiological phenomena in the neo-sphincter created from the gracilis muscle.}, journal = {Polski przeglad chirurgiczny}, volume = {88}, number = {2}, pages = {68-76}, doi = {10.1515/pjs-2016-0030}, pmid = {27213252}, issn = {2299-2847}, mesh = {Adult ; Aged ; Anal Canal/*surgery ; *Electric Stimulation Therapy ; *Electromyography ; Fecal Incontinence/*surgery ; Female ; Gracilis Muscle/*physiology/*transplantation ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/physiology/*transplantation ; }, abstract = {UNLABELLED: The aim of the study was to compare the electrophysiological phenomena occurring in the gracilis muscle, transposed into the pelvic floor during the graciloplasty procedure, subjected to continuous electrical stimulation by means of implanted stimulator, or regular stimulation by means of an external device, as well as the long-term functional results of the graciloplasty procedure.<br><br>MATERIAL AND METHODS: A total of 27 patients were included in the analysis. The study group consisted of 7 patients after dynamic graciloplasty, 11 patients after graciloplasty followed by transrectal stimulation, 4 patients after graciloplasty with transcutaneous stimulation, and 5 patients after graciloplasty without any stimulation. All patients had a surface electromyographic examination of the transposed gracilis muscle performed, the signal for each patient was compared to the signal acquisited from a non-transposed gracilis in the same patient. In addition, each subject underwent a clinical operation results assessment, as well as an anorectal manometry examination.<br><br>RESULTS: In the electromiographic examination, the mean frequency of motor units action potentials of the gracilis muscle in the thigh was 64 Hz, and in the muscle after transposition and stimulation period mean frequency was 62 Hz. There was no statistically significant difference in the frequency of action potentials before and after treatment in any of the analyzed groups, or between groups with different methods of stimulation (p> 0.05). We found a significant correlation between the clinical outcome of the procedure, and the average amplitude of the EMG signal from the transposed muscle, as well as between the amplitude of the EMG signal and the basal pressure in the anal canal in manometric examination. There were no significant correlations in the remaining manometric parameters.<br><br>CONCLUSIONS: Despite the different methods of postoperative stimulation, including expensive implantable stimulators, there was no difference in the electrical activity between the transposed gracilis muscle, and the gracilis muscle left in situ. There was no signoficant advantage of the dynamic graciloplasty procedure over the graciloplasty with transanal or transcutaneous stimulation.}, }
@article {pmid27212111, year = {2016}, author = {Buonomo, EL and Petri, WA}, title = {The microbiota and immune response during Clostridium difficile infection.}, journal = {Anaerobe}, volume = {41}, number = {}, pages = {79-84}, pmid = {27212111}, issn = {1095-8274}, support = {R21 AI114734/AI/NIAID NIH HHS/United States ; T32 AI007496/AI/NIAID NIH HHS/United States ; R01 AI026649/AI/NIAID NIH HHS/United States ; F31 AI114203/AI/NIAID NIH HHS/United States ; R01 AI124214/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Animals ; Clostridioides difficile/*immunology ; Colitis/immunology/microbiology/therapy ; Disease Susceptibility ; Enterocolitis, Pseudomembranous/immunology/*microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunity, Innate ; }, abstract = {Clostridium difficile is a gram-positive, spore forming anaerobe that infects the gut when the normal microbiota has been disrupted. C. difficile infection (CDI) is the most common cause of hospital acquired infection in the United States, and the leading cause of death due to gastroenteritis. Patients suffering from CDI have varying symptoms which range from mild diarrhea to pseudomembranous colitis and death. The involvement of the immune response to influence disease severity is just beginning to be investigated. There is evidence that the immune response can facilitate either protective or pathogenic phenotypes, suggesting it plays a multifaceted role during CDI. In addition to the immune response, the microbiota is pivotal in dictating the pathogenesis to CDI. A healthy microbiota effectively inhibits infection by restricting the ability of C. difficile to expand in the colon. Thus, understanding which immune mediators and components of the microbiota play beneficial roles during CDI will be important to future therapeutic developments. This review outlines how the microbiota can modulate specific immune mediators, such as IL-23 and others, to influence disease outcome.}, }
@article {pmid27210745, year = {2016}, author = {Möhle, L and Mattei, D and Heimesaat, MM and Bereswill, S and Fischer, A and Alutis, M and French, T and Hambardzumyan, D and Matzinger, P and Dunay, IR and Wolf, SA}, title = {Ly6C(hi) Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis.}, journal = {Cell reports}, volume = {15}, number = {9}, pages = {1945-1956}, doi = {10.1016/j.celrep.2016.04.074}, pmid = {27210745}, issn = {2211-1247}, mesh = {Adoptive Transfer ; Aging/*physiology ; Animals ; Anti-Bacterial Agents/*pharmacology ; Antibiosis/drug effects ; Antigens, Ly/*metabolism ; Brain/drug effects/physiology ; Cell Count ; Cells, Cultured ; Coculture Techniques ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Gastrointestinal Tract/drug effects/physiology ; Hippocampus/drug effects/*physiology ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes/*metabolism ; Neural Stem Cells/cytology/drug effects/metabolism ; Neurogenesis/*drug effects ; Physical Conditioning, Animal ; Probiotics/pharmacology ; Spheroids, Cellular/cytology/drug effects ; }, abstract = {Antibiotics, though remarkably useful, can also cause certain adverse effects. We detected that treatment of adult mice with antibiotics decreases hippocampal neurogenesis and memory retention. Reconstitution with normal gut flora (SPF) did not completely reverse the deficits in neurogenesis unless the mice also had access to a running wheel or received probiotics. In parallel to an increase in neurogenesis and memory retention, both SPF-reconstituted mice that ran and mice supplemented with probiotics exhibited higher numbers of Ly6C(hi) monocytes in the brain than antibiotic-treated mice. Elimination of Ly6C(hi) monocytes by antibody depletion or the use of knockout mice resulted in decreased neurogenesis, whereas adoptive transfer of Ly6C(hi) monocytes rescued neurogenesis after antibiotic treatment. We propose that the rescue of neurogenesis and behavior deficits in antibiotic-treated mice by exercise and probiotics is partially mediated by Ly6C(hi) monocytes.}, }
@article {pmid27209237, year = {2016}, author = {Kauff, DW and Kronfeld, K and Gorbulev, S and Wachtlin, D and Lang, H and Kneist, W}, title = {Continuous intraoperative monitoring of pelvic autonomic nerves during TME to prevent urogenital and anorectal dysfunction in rectal cancer patients (NEUROS): a randomized controlled trial.}, journal = {BMC cancer}, volume = {16}, number = {}, pages = {323}, pmid = {27209237}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anal Canal/innervation ; Autonomic Pathways ; Digestive System Surgical Procedures/*adverse effects ; Fecal Incontinence/prevention &amp; control ; Female ; Humans ; Lower Urinary Tract Symptoms/prevention &amp; control ; Male ; Middle Aged ; Monitoring, Intraoperative/*methods ; Organ Sparing Treatments/*methods ; Pelvis/*innervation ; Peripheral Nerve Injuries/prevention &amp; control ; Prospective Studies ; Quality of Life ; Rectal Neoplasms/*surgery ; Sexual Dysfunction, Physiological/prevention &amp; control ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Urinary, sexual and anorectal sequelae are frequent after rectal cancer surgery and were found to be related to intraoperative neurogenic impairment. Neuromonitoring methods have been developed to identify and preserve the complex pelvic autonomic nervous system in order to maintain patients' quality of life. So far no randomized study has been published dealing with the role of neuromonitoring in rectal cancer surgery.<br><br>METHODS/DESIGN: NEUROS is a prospective two-arm randomized controlled multicenter clinical trial comparing the functional outcome in rectal cancer patients undergoing total mesorectal excision (TME) with and without pelvic intraoperative neuromonitoring (pIONM). A total of 188 patients will be included. Primary endpoint is the urinary function measured by the International Prostate Symptom Score. Secondary endpoints consist of sexual, anorectal functional outcome and safety, especially oncologic safety and quality of TME. Sexual function is assessed in females with the Female Sexual Function Index and in males with the International Index of Erectile Function. For evaluation of anorectal function the Wexner-Vaizey score is used. Functional evaluation is scheduled before radiochemotherapy (if applicable), preoperatively (baseline), before hospital discharge, 3 and 6&#xa0;months after stoma closure and 12&#xa0;months after surgery. For assessment of safety adverse events, the rates of positive resection margins and quality of mesorectum are documented.<br><br>DISCUSSION: This study will provide high quality evidence on the efficacy of pIONM aiming for improvement of functional outcome in rectal cancer patients undergoing TME.<br><br>TRIAL REGISTRATION: Clinicaltrials.gov: NCT01585727 . Registration date is 04/25/2012.}, }
@article {pmid27203841, year = {2016}, author = {Pérez-Gracia, MT and Suay-García, B and García, M and Mateos-Lindemann, ML}, title = {Hepatitis E: latest developments in knowledge.}, journal = {Future microbiology}, volume = {11}, number = {}, pages = {789-808}, doi = {10.2217/fmb-2016-0012}, pmid = {27203841}, issn = {1746-0921}, mesh = {Animals ; Antiviral Agents/therapeutic use ; Hepatitis E/drug therapy/prevention &amp; control/*virology ; Hepatitis E virus/drug effects/genetics/*physiology ; Humans ; }, abstract = {Hepatitis E, caused by Hepatitis E virus (HEV), is a highly prevalent disease in developing countries. In developed nations, autochthonous HEV infections seem to be an emergent disease. Its clinical manifestations and epidemiology are well known for endemic countries. It has been confirmed that hepatitis E is a zoonosis and that parenteral transmission can also occur. The molecular mechanisms of HEV replication are not fully understood, mostly because there are no efficient cell culture systems. HEV can cause chronic hepatitis in organ transplant recipients and immunocompetent patients. Cases with fulminant hepatitis and other extrahepatic manifestations have also been reported. The diagnosis is based on serological studies and detection of HEV RNA in blood and feces. Treatment with ribavirin and/or pegylated-IFN-α have proven to be successful in some cases. The recently approved/marketed vaccine is a good option in order to prevent this infection.}, }
@article {pmid27203411, year = {2016}, author = {Ejtahed, HS and Soroush, AR and Angoorani, P and Larijani, B and Hasani-Ranjbar, S}, title = {Gut Microbiota as a Target in the Pathogenesis of Metabolic Disorders: A New Approach to Novel Therapeutic Agents.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {48}, number = {6}, pages = {349-358}, doi = {10.1055/s-0042-107792}, pmid = {27203411}, issn = {1439-4286}, mesh = {Animals ; Diabetes Mellitus/microbiology ; *Gastrointestinal Microbiome ; Humans ; Metabolic Diseases/*drug therapy/*microbiology ; Obesity/microbiology ; Osteoporosis/microbiology ; }, abstract = {As the prevalence of metabolic disorders increases dramatically, the importance of identifying environmental factors affecting metabolism control becomes greater accordingly. Gut microbiota, a complex ecosystem inhabiting the human gastrointestinal tract, is one of these potential factors. Recently, the evidence has shown the associations between alteration in gut microbiota composition and obesity, diabetes, and osteoporosis. However, the causality of gut microbiota on metabolic health has yet to be explored in intervention studies and the underlying mechanisms need to be investigated more in depth. Gut microbiota plays critical roles in the control of immunity, food intake, lipid accumulation, production of short chain fatty acids, insulin signaling, and regulation of bone mass. The gut microbiota represents a novel potential therapeutic strategy for the treatment of metabolic disorders. In this review, we provide insights into the role of the gut microbiota in metabolic disorders and its modulating interventions such as prebiotics, probiotics, and fecal microbiota transplantation.}, }
@article {pmid27197569, year = {2017}, author = {César Pereira Santos, H and Nunes Vieira Almeida, T and Souza Fiaccadori, F and das Dôres de Paula Cardoso, D and de Moraes Arantes, A and Delleon da Silva, H and Resende Alo Nagib, P and Souza, M}, title = {Adenovirus infection among allogeneic stem cell transplant recipients.}, journal = {Journal of medical virology}, volume = {89}, number = {2}, pages = {298-303}, doi = {10.1002/jmv.24579}, pmid = {27197569}, issn = {1096-9071}, mesh = {Adenovirus Infections, Human/*epidemiology/pathology/virology ; Adenoviruses, Human/classification/isolation &amp; purification ; Adolescent ; Adult ; Blood/virology ; Brazil ; Child ; Child, Preschool ; Diarrhea/virology ; Feces/virology ; Female ; Genotype ; Graft vs Host Disease/virology ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Stem Cell Transplantation/*adverse effects ; *Transplant Recipients ; Transplantation, Homologous/*adverse effects ; Viral Load ; Young Adult ; }, abstract = {The human adenovirus (HAdV) infection can cause severe disease in immunocompromised patients, such as those undergoing allogeneic hematopoietic stem cell transplant (ASCT). The main objective of this study was to prospectively monitor ASCT recipients for HAdV occurrence in a reference center in Brazil, and also to correlate viral positivity, viral load, molecular variant, clinical symptoms, and patients' prognosis. From October/2012 to October/2014, blood and feces of 21 ASCT recipients were screened for HAdV by Nested-PCR. Viral loads were determined by real-time PCR. In total, 57% of the patients had at least one positive sample (serum or feces) for HAdV. Patients presented significantly higher viral load in feces when compared to serum. Positive samples were characterized as HAdVs of species HAdV-C, -D, and -F. The main clinical symptom presented by infected patients was diarrhea, and Graft-versus-host disease (GVHD) was the main intercurrence. An association was observed between HAdV-positivity and diarrhea and also between HAdV-positivity and GVHD. Results from this study may contribute to a better understanding of the HAdV infection pattern in patients submitted to ASCT. Data therein highlight the importance of including HAdV testing during all routine laboratory exams performed on ASCT patients. J. Med. Virol. 89:298-303, 2017. © 2016 Wiley Periodicals, Inc.}, }
@article {pmid27194729, year = {2016}, author = {Shono, Y and Docampo, MD and Peled, JU and Perobelli, SM and Velardi, E and Tsai, JJ and Slingerland, AE and Smith, OM and Young, LF and Gupta, J and Lieberman, SR and Jay, HV and Ahr, KF and Porosnicu Rodriguez, KA and Xu, K and Calarfiore, M and Poeck, H and Caballero, S and Devlin, SM and Rapaport, F and Dudakov, JA and Hanash, AM and Gyurkocza, B and Murphy, GF and Gomes, C and Liu, C and Moss, EL and Falconer, SB and Bhatt, AS and Taur, Y and Pamer, EG and van den Brink, MRM and Jenq, RR}, title = {Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice.}, journal = {Science translational medicine}, volume = {8}, number = {339}, pages = {339ra71}, pmid = {27194729}, issn = {1946-6242}, support = {R01 AI101406/AI/NIAID NIH HHS/United States ; R01 HL069929/HL/NHLBI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; R01 AI080455/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R00 CA176376/CA/NCI NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; R01 AI100288/AI/NIAID NIH HHS/United States ; K08 HL115355/HL/NHLBI NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; K08 CA184420/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents ; CD4-Positive T-Lymphocytes/metabolism ; Cilastatin/therapeutic use ; Cilastatin, Imipenem Drug Combination ; Colon/microbiology ; Drug Combinations ; Feces/microbiology ; Female ; Flow Cytometry ; Gastrointestinal Microbiome/drug effects ; Graft vs Host Disease/etiology/*microbiology/*mortality ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Imipenem/therapeutic use ; Interleukin-23 ; Mice ; Mice, Inbred C57BL ; Penicillanic Acid/analogs &amp; derivatives/therapeutic use ; Phylogeny ; Piperacillin/therapeutic use ; Piperacillin, Tazobactam Drug Combination ; Transplantation, Homologous/*adverse effects ; Verrucomicrobia/classification/drug effects/genetics ; }, abstract = {Intestinal bacteria may modulate the risk of infection and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients often develop neutropenic fever, which is treated with antibiotics that may target anaerobic bacteria in the gut. We retrospectively examined 857 allo-HSCT recipients and found that treatment of neutropenic fever with imipenem-cilastatin and piperacillin-tazobactam antibiotics was associated with increased GVHD-related mortality at 5 years (21.5% for imipenem-cilastatin-treated patients versus 13.1% for untreated patients, P = 0.025; 19.8% for piperacillin-tazobactam-treated patients versus 11.9% for untreated patients, P = 0.007). However, two other antibiotics also used to treat neutropenic fever, aztreonam and cefepime, were not associated with GVHD-related mortality (P = 0.78 and P = 0.98, respectively). Analysis of stool specimens from allo-HSCT recipients showed that piperacillin-tazobactam administration was associated with perturbation of gut microbial composition. Studies in mice demonstrated aggravated GVHD mortality with imipenem-cilastatin or piperacillin-tazobactam compared to aztreonam (P < 0.01 and P < 0.05, respectively). We found pathological evidence for increased GVHD in the colon of imipenem-cilastatin-treated mice (P < 0.05), but no difference in the concentration of short-chain fatty acids or numbers of regulatory T cells. Notably, imipenem-cilastatin treatment of mice with GVHD led to loss of the protective mucus lining of the colon (P < 0.01) and the compromising of intestinal barrier function (P < 0.05). Sequencing of mouse stool specimens showed an increase in Akkermansia muciniphila (P < 0.001), a commensal bacterium with mucus-degrading capabilities, raising the possibility that mucus degradation may contribute to murine GVHD. We demonstrate an underappreciated risk for the treatment of allo-HSCT recipients with antibiotics that may exacerbate GVHD in the colon.}, }
@article {pmid27194400, year = {2016}, author = {Manges, AR and Steiner, TS and Wright, AJ}, title = {Fecal microbiota transplantation for the intestinal decolonization of extensively antimicrobial-resistant opportunistic pathogens: a review.}, journal = {Infectious diseases (London, England)}, volume = {48}, number = {8}, pages = {587-592}, doi = {10.1080/23744235.2016.1177199}, pmid = {27194400}, issn = {2374-4243}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria/drug effects/pathogenicity ; Bacterial Infections/microbiology/*therapy ; *Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Diseases/microbiology/*therapy ; Gastrointestinal Microbiome/physiology ; Humans ; Immunocompromised Host ; Male ; Middle Aged ; Opportunistic Infections/microbiology/*therapy ; }, abstract = {Treatment options for multidrug-resistant (MDR) bacterial infections are limited and often less effective. Non-pharmacologic approaches to preventing or treating MDR infections are currently restricted to improved antimicrobial stewardship and infection control practices. Fecal microbiota transplantation (FMT), a highly effective treatment for recurrent Clostridium difficile infection, has emerged as a promising therapy for intestinal MDR bacterial decolonization. A total of eight case reports have been published showing FMT resulted in intestinal decolonization of extended spectrum β-lactamase (ESBL)-producing and carbapenemase-producing Enterobacteriaceae, vancomycin-resistant Enterococci, or methicillin-resistant Staphylococcus aureus. The procedure has been shown to work even in immunocompromised patients and those experiencing medical crises without any adverse events. Five trials are currently underway to further investigate the use of FMT for MDR bacterial decolonization. FMT is a completely novel way to eradicate drug-resistant bacteria from the intestinal reservoir and should be further investigated to address the global problem of difficult-to-treat, MDR bacterial infections.}, }
@article {pmid27191490, year = {2016}, author = {Pilcher, H}, title = {Q&amp;A: Peter Whorwell.}, journal = {Nature}, volume = {533}, number = {7603}, pages = {S112-3}, pmid = {27191490}, issn = {1476-4687}, mesh = {Amitriptyline/therapeutic use ; Diet/adverse effects ; Fecal Microbiota Transplantation ; Humans ; Hypnosis ; *Irritable Bowel Syndrome/diagnosis/microbiology/physiopathology/psychology/therapy ; United Kingdom ; }, }
@article {pmid27188820, year = {2016}, author = {Ray, K}, title = {Gut microbiota: FMT - enduring strains.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {13}, number = {7}, pages = {376}, pmid = {27188820}, issn = {1759-5053}, mesh = {*Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Microbiota ; }, }
@article {pmid27185076, year = {2016}, author = {Fischer, M and Kao, D and Mehta, SR and Martin, T and Dimitry, J and Keshteli, AH and Cook, GK and Phelps, E and Sipe, BW and Xu, H and Kelly, CR}, title = {Predictors of Early Failure After Fecal Microbiota Transplantation for the Therapy of Clostridium Difficile Infection: A Multicenter Study.}, journal = {The American journal of gastroenterology}, volume = {111}, number = {7}, pages = {1024-1031}, pmid = {27185076}, issn = {1572-0241}, support = {R21 DK093839/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Clostridioides difficile/isolation &amp; purification/pathogenicity ; Diarrhea/diagnosis/microbiology ; *Enterocolitis, Pseudomembranous/microbiology/physiopathology/therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Patient Care Planning ; Prognosis ; Recurrence ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Treatment Failure ; United States ; }, abstract = {OBJECTIVES: Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent or refractory Clostridium difficile infection (CDI); however, 10-20% of patients fail to achieve cure after a single FMT. The aim of this study was to identify risk factors associated with FMT failure and to develop and validate a prediction model for FMT failure.<br><br>METHODS: Patient characteristics, CDI history, FMT characteristics, and outcomes data for patients treated between 2011 and 2015 at three academic tertiary referral centers were prospectively collected. Early FMT failure was defined as non-response or recurrence of diarrhea associated with positive stool C. difficile toxin or PCR within 1 month of FMT. Late FMT failure was defined as recurrence of diarrhea associated with positive stool C. difficile toxin or PCR between 1 and 3 months of the FMT. Patient data from two centers were used to determine independent predictors of FMT failure and to build a prediction model. A risk index was constructed based on coefficients of final predictors. The patient cohort from the third center was used to validate the prediction model.<br><br>RESULTS: Of 328 patients in the developmental cohort, 73.5% (N=241) were females with a mean age of 61.4&#xb1;19.3 years; 19.2% (N=63) had inflammatory bowel disease (IBD), and 23.5% (N=77) were immunocompromised. The indication for FMT was recurrent CDI in 87.2% (N=286) and severe or severe-complicated in 12.8% (N=42). FMT was performed as an inpatient in 16.7% (N=54). The stool source was patient-directed donors in 40% (N=130) of cases. The early FMT failure rate was 18.6%, and the late failure rate was 2.7%. In the multivariable analysis, predictors of early FMT failure included severe or severe-complicated CDI (odds ratio (OR) 5.95, 95% confidence interval (CI): 2.26-15.62), inpatient status during FMT (OR 3.78, 95% CI: 1.55-9.24), and previous CDI-related hospitalization (OR 1.43, 95% CI: 1.18-1.75); with each additional hospitalization, the odds of failure increased by 43%. Risk scores ranged from 0 to 13, with 0 indicating low risk, 1-2 indicating moderate risk, and &#x2265;3 indicating high risk. In the developmental cohort, early FMT failure rates were 5.6% for low risk, 12.7% for moderate risk, and 41% for high-risk patients. Of 134 patients in the validation cohort, 57% (N=77) were females with a mean age of 66&#xb1;18.1 years; 9.7% (N=13) had IBD, and 17.9% (N=24) were immunocompromised. The early FMT failure rate at 1 month was 19.4%, with an additional 3% failing by 3 months. In the validation cohort, FMT failure rates were 2.1% for low risk, 16.1% for moderate risk, and 35.7% for high risk patients. The area under the receiver operating characteristic curve (AUROC) for FMT failure was 0.81 in the developmental cohort and 0.84 in the validation cohort.<br><br>CONCLUSIONS: Severe and severe-complicated indication, inpatient status during FMT, and the number of previous CDI-related hospitalizations are strongly associated with early failure of a single FMT for CDI. The novel prediction model has good discriminative power at identifying individuals who are at high risk of failure after FMT therapy and may assist the treating physician in subsequent management plans.}, }
@article {pmid27183608, year = {2016}, author = {Ihara, S and Hirata, Y and Serizawa, T and Suzuki, N and Sakitani, K and Kinoshita, H and Hayakawa, Y and Nakagawa, H and Ijichi, H and Tateishi, K and Koike, K}, title = {TGF-β Signaling in Dendritic Cells Governs Colonic Homeostasis by Controlling Epithelial Differentiation and the Luminal Microbiota.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {196}, number = {11}, pages = {4603-4613}, doi = {10.4049/jimmunol.1502548}, pmid = {27183608}, issn = {1550-6606}, mesh = {Animals ; Cell Differentiation ; Colitis/chemically induced/immunology/microbiology ; Colon/*cytology/immunology/*microbiology ; Dendritic Cells/immunology/*metabolism ; Dextran Sulfate ; Disease Models, Animal ; Epithelial Cells/*cytology ; *Gastrointestinal Microbiome/immunology ; *Homeostasis ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; *Signal Transduction ; Transforming Growth Factor beta/*immunology ; }, abstract = {Dendritic cells (DCs) mediate host immune responses to gut microbes and play critical roles in inflammatory bowel disease. In this study, we examined the role of TGF-β signaling in DCs in colonic homeostasis. CD11c-cre Tgfbr2(fl/fl) mice developed spontaneous colitis, and CD11c-cre Tgfbr2(fl/+) mice exhibited susceptibility to dextran sulfate sodium-induced colitis. Colitis in these mice was characterized by goblet cell depletion and dysbiosis caused by Enterobacteriaceae enrichment. Wild-type mice gavaged with Enterobacteriaceae from CD11c-cre Tgfbr2(fl/fl) mice feces showed severe colitis after dextran sulfate sodium treatment, whereas those treated with Notch inhibitor exhibited attenuated colonic injury with increased goblet cell numbers, thickened mucus layer, and fewer fecal Enterobacteriaceae Wild-type mice transplanted with CD11c-cre Tgfbr2(fl/fl) bone marrow developed colitis showing increased Jagged1 and Jagged2 in DCs, increased Hes1 levels in epithelium, and goblet cell depletion. These findings suggest that TGF-β signaling in DCs regulates intestinal homeostasis by modulating epithelial cell differentiation and fecal microbiota.}, }
@article {pmid27180657, year = {2016}, author = {Spinler, JK and Ross, CL and Savidge, TC}, title = {Probiotics as adjunctive therapy for preventing Clostridium difficile infection - What are we waiting for?.}, journal = {Anaerobe}, volume = {41}, number = {}, pages = {51-57}, pmid = {27180657}, issn = {1095-8274}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 AI100914/AI/NIAID NIH HHS/United States ; R21 DK096323/DK/NIDDK NIH HHS/United States ; T32 DK007664/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Clinical Trials as Topic ; Clostridioides difficile/*physiology ; Enterocolitis, Pseudomembranous/*prevention &amp; control ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Probiotics/*therapeutic use ; }, abstract = {UNLABELLED: With the end of the golden era of antibiotic discovery, the emergence of a new post-antibiotic age threatens to thrust global health and modern medicine back to the pre-antibiotic era. Antibiotic overuse has resulted in the natural evolution and selection of multi-drug resistant bacteria. One major public health threat, Clostridium difficile, is now the single leading cause of hospital-acquired bacterial infections and is by far the most deadly enteric pathogen for the U.S.<br><br>POPULATION: Due to the high morbidity and mortality and increasing incidence that coincides with antibiotic use, non-traditional therapeutics are ideal alternatives to current treatment methods and also provide an avenue towards prevention. Despite the need for alternative therapies to antibiotics and the safety of most probiotics on the market, researchers are inundated with regulatory issues that hinder the translational science required to push these therapies forward. This review discusses the regulatory challenges of probiotic research, expert opinion regarding the application of probiotics to C.&#xa0;difficile infection and the efficacy of probiotics in preventing this disease.}, }
@article {pmid27180007, year = {2016}, author = {Spinler, JK and Brown, A and Ross, CL and Boonma, P and Conner, ME and Savidge, TC}, title = {Administration of probiotic kefir to mice with Clostridium difficile infection exacerbates disease.}, journal = {Anaerobe}, volume = {40}, number = {}, pages = {54-57}, pmid = {27180007}, issn = {1095-8274}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 AI100914/AI/NIAID NIH HHS/United States ; R21 DK096323/DK/NIDDK NIH HHS/United States ; UL1 RR029876/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Clostridioides difficile/*drug effects/growth &amp; development/pathogenicity ; Colony Count, Microbial ; Disease Models, Animal ; Disease Progression ; Enterocolitis, Pseudomembranous/microbiology/mortality/*pathology ; Female ; Gastrointestinal Microbiome/drug effects ; Kefir/*adverse effects ; Mice ; Mice, Inbred C57BL ; Probiotics/*adverse effects ; Severity of Illness Index ; Survival Analysis ; }, abstract = {Lifeway(®) kefir, a fermented milk product containing 12 probiotic organisms, is reported to show promise as an alternative to fecal microbiota transplantation for recurrent Clostridium difficile infection (CDI). We employed a murine CDI model to study the probiotic protective mechanisms and unexpectedly determined that kefir drastically increased disease severity. Our results emphasize the need for further independent clinical testing of kefir as alternative therapy in recurrent CDI.}, }
@article {pmid27176607, year = {2016}, author = {Shen, TC and Chehoud, C and Ni, J and Hsu, E and Chen, YY and Bailey, A and Laughlin, A and Bittinger, K and Bushman, FD and Wu, GD}, title = {Dietary Regulation of the Gut Microbiota Engineered by a Minimal Defined Bacterial Consortium.}, journal = {PloS one}, volume = {11}, number = {5}, pages = {e0155620}, pmid = {27176607}, issn = {1932-6203}, support = {P30 DK050306/DK/NIDDK NIH HHS/United States ; R01 GM103591/GM/NIGMS NIH HHS/United States ; T32 DK007066/DK/NIDDK NIH HHS/United States ; }, mesh = {Ammonia/metabolism ; Animals ; Colony Count, Microbial ; *Diet ; Diet, Protein-Restricted ; Feces/enzymology/microbiology ; Female ; *Gastrointestinal Microbiome ; Metabolic Engineering/*methods ; Mice, Inbred C57BL ; Mice, SCID ; *Microbial Consortia ; Nitrogen/metabolism ; Time Factors ; Urease/metabolism ; }, abstract = {We have recently reported that Altered Schaedler Flora (ASF) can be used to durably engineer the gut microbiota to reduce ammonia production as an effective modality to reduce morbidity and mortality in the setting of liver injury. Here we investigated the effects of a low protein diet on ASF colonization and its ability to engineer the microbiota. Initially, ASF inoculation was similar between mice fed a normal protein diet or low protein diet, but the outgrowth of gut microbiota differed over the ensuing month. Notable was the inability of the dominant Parabacteroides ASF taxon to exclude other taxa belonging to the Bacteroidetes phylum in the setting of a low protein diet. Instead, a poorly classified yet highly represented Bacteroidetes family, S24-7, returned within 4 weeks of inoculation in mice fed a low protein diet, demonstrating a reduction in ASF resilience in response to dietary stress. Nevertheless, fecal ammonia levels remained significantly lower than those observed in mice on the same low protein diet that received a transplant of normal feces. No deleterious effects were observed in host physiology due to ASF inoculation into mice on a low protein diet. In total, these results demonstrate that low protein diet can have a pronounced effect on engineering the gut microbiota but modulation of ammonia is preserved.}, }
@article {pmid27173141, year = {2016}, author = {Yoon, MY and Min, KB and Lee, KM and Yoon, Y and Kim, Y and Oh, YT and Lee, K and Chun, J and Kim, BY and Yoon, SH and Lee, I and Kim, CY and Yoon, SS}, title = {A single gene of a commensal microbe affects host susceptibility to enteric infection.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {11606}, pmid = {27173141}, issn = {2041-1723}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Catalase/genetics ; Disease Models, Animal ; Disease Susceptibility/*microbiology ; Enterocolitis ; Escherichia coli/*genetics/metabolism ; Fecal Microbiota Transplantation/methods ; Female ; Gastroenteritis/*microbiology ; Gastrointestinal Microbiome/drug effects/*genetics ; Gene Knockout Techniques ; Humans ; Intestinal Mucosa/drug effects/microbiology ; Intestines/microbiology ; Lactose/metabolism ; Mice ; Mice, Inbred BALB C ; Symbiosis/*genetics ; Vibrio cholerae/*pathogenicity ; }, abstract = {Indigenous microbes inside the host intestine maintain a complex self-regulating community. The mechanisms by which gut microbes interact with intestinal pathogens remain largely unknown. Here we identify a commensal Escherichia coli strain whose expansion predisposes mice to infection by Vibrio cholerae, a human pathogen. We refer to this strain as 'atypical' E. coli (atEc) because of its inability to ferment lactose. The atEc strain is resistant to reactive oxygen species (ROS) and proliferates extensively in antibiotic-treated adult mice. V. cholerae infection is more severe in neonatal mice transplanted with atEc compared with those transplanted with a typical E. coli strain. Intestinal ROS levels are decreased in atEc-transplanted mice, favouring proliferation of ROS-sensitive V. cholerae. An atEc mutant defective in ROS degradation fails to facilitate V. cholerae infection when transplanted, suggesting that host infection susceptibility can be regulated by a single gene product of one particular commensal species.}, }
@article {pmid27172442, year = {2016}, author = {Šturdík, I and Hlavatý, T and Payer, J}, title = {[Fecal microbiota transplantation].}, journal = {Vnitrni lekarstvi}, volume = {62}, number = {2}, pages = {147-151}, pmid = {27172442}, issn = {0042-773X}, mesh = {Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapeutic method, in which the fecal microflora from healthy donors is transmitted to the patient to restore the healthy microbial composition of the gut. In the recent years, there is a growing interest in the therapeutic potential of FMT in various diseases. The standard FMT protocols do not exist. Procedures of FMT vary in several aspects such as donor selection, preparation of fecal material, preparation of the recipient and administration way. FMT appears to be the most successful in the treatment of recurrent Clostridium difficile infection (CDI), randomized controlled studies reported 90 % success rate. There is a limited evidence for FMT as a treatment of ulcerative colitis. FMT has been also studied as treatment of diseases with impaired gut microbiota, such as cardiovascular, autoimmune and metabolic diseases. Many unanswered questions with regard to FMT remain and further research is needed.}, }
@article {pmid27169388, year = {2016}, author = {Wagner-Döbler, I}, title = {Biofilm transplantation in the deep sea.}, journal = {Molecular ecology}, volume = {25}, number = {9}, pages = {1905-1907}, doi = {10.1111/mec.13612}, pmid = {27169388}, issn = {1365-294X}, mesh = {Bacteria/genetics ; *Biofilms ; Indian Ocean ; *Metagenome ; Microbiota ; }, abstract = {A gold rush is currently going on in microbial ecology, which is powered by the possibility to determine the full complexity of microbial communities through next-generation sequencing. Accordingly, enormous efforts are underway to describe microbiomes worldwide, in humans, animals, plants, soil, air and the ocean. While much can be learned from these studies, only experiments will finally unravel mechanisms. One of the key questions is how a microbial community is assembled from a pool of bacteria in the environment, and how it responds to change - be it the increase in CO2 concentration in the ocean, or antibiotic treatment of the gut microbiome. The study by Zhang et al. () in this issue is one of the very few that approaches this problem experimentally in the natural environment. The authors selected a habitat which is both extremely interesting and difficult to access. They studied the Thuwal Seep in the Red Sea at 850 m depth and used a remotely operated vehicle (ROV) to place a steel frame carrying substrata for biofilm growth into the brine pool and into the adjacent normal bottom water (NBW). Biofilms were allowed to develop for 3 days, and then those that had been growing in the brine pool were transported to normal bottom water and stayed there for another 3 days, and vice versa. The 'switched' biofilms were then compared with their source communities by metagenome sequencing. Strikingly, both 'switched' biofilms were now dominated by the same two species. These species were able to cope with conditions in both source ecosystems, as shown by assembly of their genomes and detection of expression of key genes. The biofilms had adapted to environmental change, rather than to brine pools or NBW. The study shows both the resilience and adaptability of biofilm communities and has implications for microbial ecology in general and even for therapeutic approaches such as transplantation of faecal microbiomes.}, }
@article {pmid27167101, year = {2016}, author = {Gräs, S and Lose, G}, title = {Does regenerative medicine have a potential role in the treatment of anal incontinence?.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {18}, number = {6}, pages = {625-626}, doi = {10.1111/codi.13379}, pmid = {27167101}, issn = {1463-1318}, mesh = {Anal Canal/physiopathology ; Animals ; Bioengineering ; Fecal Incontinence/*therapy ; Humans ; Mesenchymal Stem Cell Transplantation ; Models, Animal ; Muscle Fibers, Skeletal/physiology ; *Regenerative Medicine ; }, }
@article {pmid27161356, year = {2016}, author = {Fuentes, S and de Vos, WM}, title = {How to Manipulate the Microbiota: Fecal Microbiota Transplantation.}, journal = {Advances in experimental medicine and biology}, volume = {902}, number = {}, pages = {143-153}, doi = {10.1007/978-3-319-31248-4_10}, pmid = {27161356}, issn = {0065-2598}, mesh = {Clostridioides difficile/pathogenicity/physiology ; Dysbiosis/microbiology/pathology/*therapy ; Enterocolitis, Pseudomembranous/microbiology/pathology/*therapy ; Fecal Microbiota Transplantation/ethics/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Gastrointestinal Tract/microbiology ; Humans ; Inflammatory Bowel Diseases/microbiology/pathology/*therapy ; Tissue Donors ; }, abstract = {Fecal microbiota transplantation (FMT) is a rather straightforward therapy that manipulates the human gastrointestinal (GI) microbiota, by which a healthy donor microbiota is transferred into an existing but disturbed microbial ecosystem. This is a natural process that occurs already at birth; infants are rapidly colonized by a specific microbial community, the composition of which strongly depends on the mode of delivery and which therefore most likely originates from the mother (Palmer et al. 2007; Tannock et al. 1990). Since this early life microbial community already contains most, if not all, of the predominantly anaerobic microbes that are only found in the GI tract, it is reasonable to assume that early life colonization is the ultimate natural fecal transplantation.}, }
@article {pmid27160536, year = {2016}, author = {Filipiak, W and Mochalski, P and Filipiak, A and Ager, C and Cumeras, R and Davis, CE and Agapiou, A and Unterkofler, K and Troppmair, J}, title = {A Compendium of Volatile Organic Compounds (VOCs) Released By Human Cell Lines.}, journal = {Current medicinal chemistry}, volume = {23}, number = {20}, pages = {2112-2131}, pmid = {27160536}, issn = {1875-533X}, support = {P 24736/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Aldehyde Dehydrogenase/metabolism ; Biomarkers/analysis/blood/urine ; Cell Line ; Cytochrome P-450 Enzyme System/metabolism ; Gas Chromatography-Mass Spectrometry ; Humans ; Oxidative Stress ; Volatile Organic Compounds/*analysis ; }, abstract = {Volatile organic compounds (VOCs) offer unique insights into ongoing biochemical processes in healthy and diseased humans. Yet, their diagnostic use is hampered by the limited understanding of their biochemical or cellular origin and their frequently unclear link to the underlying diseases. Major advancements are expected from the analyses of human primary cells, cell lines and cultures of microorganisms. In this review, a database of 125 reliably identified VOCs previously reported for human healthy and diseased cells was assembled and their potential origin is discussed. The majority of them have also been observed in studies with other human matrices (breath, urine, saliva, feces, blood, skin emanations). Moreover, continuing improvements of qualitative and quantitative analyses, based on the recommendations of the ISO-11843 guidelines, are suggested for the necessary standardization of analytical procedures and better comparability of results. The data provided contribute to arriving at a more complete human volatilome and suggest potential volatile biomarkers for future validation. Dedication:This review is dedicated to the memory of Prof. Dr. Anton Amann, who sadly passed away on January 6, 2015. He was motivator and motor for the field of breath research.}, }
@article {pmid27158904, year = {2016}, author = {Lamas, B and Richard, ML and Leducq, V and Pham, HP and Michel, ML and Da Costa, G and Bridonneau, C and Jegou, S and Hoffmann, TW and Natividad, JM and Brot, L and Taleb, S and Couturier-Maillard, A and Nion-Larmurier, I and Merabtene, F and Seksik, P and Bourrier, A and Cosnes, J and Ryffel, B and Beaugerie, L and Launay, JM and Langella, P and Xavier, RJ and Sokol, H}, title = {CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands.}, journal = {Nature medicine}, volume = {22}, number = {6}, pages = {598-605}, pmid = {27158904}, issn = {1546-170X}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Animals ; CARD Signaling Adaptor Proteins/genetics/*immunology ; Chromatography, High Pressure Liquid ; Colitis/chemically induced/*immunology/pathology ; Colon/immunology/microbiology/pathology ; Cytokines/immunology ; Dextran Sulfate/toxicity ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/genetics/*immunology ; Gene Expression Profiling ; Humans ; Inflammatory Bowel Diseases/genetics/immunology ; Interleukins/*immunology ; Lactobacillus/*metabolism ; Male ; Mice ; Mice, Knockout ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Receptors, Aryl Hydrocarbon/*immunology ; Reverse Transcriptase Polymerase Chain Reaction ; Tryptophan/immunology/*metabolism ; Young Adult ; Interleukin-22 ; }, abstract = {Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9(-/-) mice are more susceptible to colitis. The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation.}, }
@article {pmid27158839, year = {2016}, author = {Smits, WK and Lyras, D and Lacy, DB and Wilcox, MH and Kuijper, EJ}, title = {Clostridium difficile infection.}, journal = {Nature reviews. Disease primers}, volume = {2}, number = {}, pages = {16020}, pmid = {27158839}, issn = {2056-676X}, support = {I01 BX002943/BX/BLRD VA/United States ; R01 AI095755/AI/NIAID NIH HHS/United States ; R37 AI095755/AI/NIAID NIH HHS/United States ; }, mesh = {Ampicillin/pharmacology/therapeutic use ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Toxins/analysis/blood ; Clindamycin/pharmacology/therapeutic use ; Clostridioides difficile/immunology/*pathogenicity ; Clostridium Infections/*diagnosis/epidemiology/*physiopathology ; Diarrhea/etiology ; Enterotoxins/analysis/blood ; Gastrointestinal Microbiome/drug effects/immunology ; Humans ; Risk Factors ; Sugar Alcohol Dehydrogenases/analysis/blood ; }, abstract = {Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota.}, }
@article {pmid27156262, year = {2016}, author = {Wiedel, N and Gilbert, J and Baloun, B and Nelson, C}, title = {Clostridium difficile Associated Diarrhea.}, journal = {South Dakota medicine : the journal of the South Dakota State Medical Association}, volume = {69}, number = {3}, pages = {124-127}, pmid = {27156262}, issn = {0038-3317}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/physiology ; Diarrhea/*diagnosis/microbiology/prevention &amp; control/*therapy ; Enterocolitis, Pseudomembranous/*diagnosis/microbiology/prevention &amp; control/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Metronidazole/therapeutic use ; Recurrence ; Vancomycin/therapeutic use ; }, abstract = {Clostridium difficile associated diarrhea (CDAD) is increasingly important in primary care, and associated with high cost, significant morbidity and mortality. As the preferred treatment for different groups of patients varies considerably, it is important to stratify CDAD patients into mild versus severe and uncomplicated versus complicated. While treatment with either metronidazole or oral vancomycin cures a majority of patients, and despite improvement in early diagnosis and therapy, recurrence continues to be a significant problem. In appropriately selected patients, fecal bacteriotherapy has emerged as an effective treatment for the patient with multiple recurrences. Addressing CDAD should include antibiotic stewardship, improved hygiene, prompt diagnosis, appropriate treatment, and infection precautions in hospitals and skilled nursing facilities.}, }
@article {pmid27154892, year = {2016}, author = {Olson, DC and Scobey, MW}, title = {The Challenge of Clostridium difficile Infection.}, journal = {North Carolina medical journal}, volume = {77}, number = {3}, pages = {206-210}, doi = {10.18043/ncm.77.3.206}, pmid = {27154892}, issn = {0029-2559}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/diagnosis/epidemiology/*therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; }, abstract = {Clostridium difficile infection is a major problem in the United States, resulting in significant morbidity, mortality, and financial costs to the health care system. This commentary provides an update regarding the epidemiology, diagnosis, current recommended management, and challenges surrounding C. difficile infection.}, }
@article {pmid27153571, year = {2016}, author = {Eng, A and Borenstein, E}, title = {An algorithm for designing minimal microbial communities with desired metabolic capacities.}, journal = {Bioinformatics (Oxford, England)}, volume = {32}, number = {13}, pages = {2008-2016}, pmid = {27153571}, issn = {1367-4811}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; }, mesh = {*Algorithms ; *Metabolic Networks and Pathways ; Microbiota/*physiology ; *Programming, Linear ; }, abstract = {MOTIVATION: Recent efforts to manipulate various microbial communities, such as fecal microbiota transplant and bioreactor systems' optimization, suggest a promising route for microbial community engineering with numerous medical, environmental and industrial applications. However, such applications are currently restricted in scale and often rely on mimicking or enhancing natural communities, calling for the development of tools for designing synthetic communities with specific, tailored, desired metabolic capacities.<br><br>RESULTS: Here, we present a first step toward this goal, introducing a novel algorithm for identifying minimal sets of microbial species that collectively provide the enzymatic capacity required to synthesize a set of desired target product metabolites from a predefined set of available substrates. Our method integrates a graph theoretic representation of network flow with the set cover problem in an integer linear programming (ILP) framework to simultaneously identify possible metabolic paths from substrates to products while minimizing the number of species required to catalyze these metabolic reactions. We apply our algorithm to successfully identify minimal communities both in a set of simple toy problems and in more complex, realistic settings, and to investigate metabolic capacities in the gut microbiome. Our framework adds to the growing toolset for supporting informed microbial community engineering and for ultimately realizing the full potential of such engineering efforts.<br><br>The algorithm source code, compilation, usage instructions and examples are available under a non-commercial research use only license at https://github.com/borenstein-lab/CoMiDA CONTACT: elbo@uw.edu<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid27152872, year = {2016}, author = {Moayyedi, P}, title = {Fecal transplantation: any real hope for inflammatory bowel disease?.}, journal = {Current opinion in gastroenterology}, volume = {32}, number = {4}, pages = {282-286}, doi = {10.1097/MOG.0000000000000285}, pmid = {27152872}, issn = {1531-7056}, mesh = {Colitis, Ulcerative/immunology/*therapy ; Crohn Disease/immunology/*therapy ; *Fecal Microbiota Transplantation/methods/trends ; Gastrointestinal Tract/*immunology ; Humans ; Intestinal Mucosa/*immunology ; Meta-Analysis as Topic ; Microbiota/immunology ; Randomized Controlled Trials as Topic ; Remission Induction/*methods ; }, abstract = {PURPOSE OF REVIEW: Fecal microbiota transplant (FMT) has emerged as an important treatment for antibiotic resistant or recurrent Clostridium difficile infection. There has been a great deal of media coverage of the efficacy of FMT, and patients with inflammatory bowel disease (IBD) understandably wonder if this approach would also work for them. There are also instructions on 'do it yourself' FMT therapy on the web. It is important to understand whether there is evidence that this approach is effective in IBD so that we can advise our patients appropriately.<br><br>RECENT FINDINGS: Systematic reviews have identified four case series involving 27 ulcerative colitis patients with a pooled remission rate of 24% (95% confidence interval (CI)&#x200a;=&#x200a;11-45%). Two randomized controlled trials evaluating a total of 123 active ulcerative colitis patients have given conflicting results but the pooled data do suggest benefit with a number needed to treat of 6 (95% CI&#x200a;=&#x200a;3-33). There are four case series involving 38 patients with Crohn's disease with a clinical response in 60.5% (95% CI&#x200a;=&#x200a;28-86%). There are no randomized trials in Crohn's disease.<br><br>SUMMARY: At present there are insufficient data to recommend FMT in IBD, and patients certainly should not be administering this themselves. This remains an interesting approach to treating IBD and more studies are needed to establish the optimal method of delivery as well as randomized, placebo controlled trials to establish the efficacy of FMT.}, }
@article {pmid27152073, year = {2016}, author = {Laszlo, M and Ciobanu, L and Andreica, V and Pascu, O}, title = {Fecal transplantation indications in ulcerative colitis. Preliminary study.}, journal = {Clujul medical (1957)}, volume = {89}, number = {2}, pages = {224-228}, pmid = {27152073}, issn = {1222-2119}, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation is used with success in persistent (more than two episodes) Clostridium Difficile Infection; it has also gained importance and started to be used in inflammatory bowel disease. There are theoretical arguments that justify its use in ulcerative colitis or Crohn's disease. Based on our clinical cases we tried to evaluate the indications of fecal microbiota transplantation young patients with ulcerative colitis and multiple relapses, in which biological or immunosuppressive treatment were ineffective.<br><br>METHODS: Five patients with moderate-severe ulcerative colitis or Clostridium Difficile infection who ceased to have a therapeutic response to biological therapy, were given fecal microbiota transplant as an alternative to biological therapy and/or immunosuppression. Fecal microbiota transplant was administered via colonoscopy using healthy donors from their family.<br><br>RESULTS: The results were favorable and spectacular in all patients and complete remission was achieved for at least 10 months. Clinical remission was achieved in all patients. Endoscopic appearance of ulcers in patients improved. In 2 patients the effect of the fecal microbiota transplant diminished after 10-12 months and the tendency to relapse appeared (3-4 stools/day, blood streaks present sometimes in the stool). Reintroduction of systemic therapy or immunosuppression demonstrated that patients regained the therapeutic response to these treatments, and remission was maintained.<br><br>CONCLUSION: Fecal microbiota transplantation can be used as salvage therapy in patients refractory to biological therapy, as elective therapy in clostridium difficile infection or as an alternative therapy in young patients with multiple relapses who have reservations regarding biological or immunosuppressive treatment.}, }
@article {pmid27151129, year = {2016}, author = {Tariq, R and Smyrk, T and Pardi, DS and Tremaine, WJ and Khanna, S}, title = {New-Onset Microscopic Colitis in an Ulcerative Colitis Patient After Fecal Microbiota Transplantation.}, journal = {The American journal of gastroenterology}, volume = {111}, number = {5}, pages = {751-752}, pmid = {27151129}, issn = {1572-0241}, mesh = {Aged ; Budesonide/*therapeutic use ; Clostridioides difficile ; Colitis, Microscopic/*drug therapy ; Colitis, Ulcerative/complications/*therapy ; Colonoscopy ; Enterocolitis, Pseudomembranous/complications/*therapy ; *Fecal Microbiota Transplantation ; Glucocorticoids/*therapeutic use ; Humans ; Male ; }, }
@article {pmid27148577, year = {2016}, author = {Broecker, F and Klumpp, J and Schuppler, M and Russo, G and Biedermann, L and Hombach, M and Rogler, G and Moelling, K}, title = {Long-term changes of bacterial and viral compositions in the intestine of a recovered Clostridium difficile patient after fecal microbiota transplantation.}, journal = {Cold Spring Harbor molecular case studies}, volume = {2}, number = {1}, pages = {a000448}, pmid = {27148577}, issn = {2373-2873}, abstract = {Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infections (RCDIs). However, long-term effects on the patients' gut microbiota and the role of viruses remain to be elucidated. Here, we characterized bacterial and viral microbiota in the feces of a cured RCDI patient at various time points until 4.5 yr post-FMT compared with the stool donor. Feces were subjected to DNA sequencing to characterize bacteria and double-stranded DNA (dsDNA) viruses including phages. The patient's microbial communities varied over time and showed little overall similarity to the donor until 7 mo post-FMT, indicating ongoing gut microbiota adaption in this time period. After 4.5 yr, the patient's bacteria attained donor-like compositions at phylum, class, and order levels with similar bacterial diversity. Differences in the bacterial communities between donor and patient after 4.5 yr were seen at lower taxonomic levels. C. difficile remained undetectable throughout the entire timespan. This demonstrated sustainable donor feces engraftment and verified long-term therapeutic success of FMT on the molecular level. Full engraftment apparently required longer than previously acknowledged, suggesting the implementation of year-long patient follow-up periods into clinical practice. The identified dsDNA viruses were mainly Caudovirales phages. Unexpectedly, sequences related to giant algae-infecting Chlorella viruses were also detected. Our findings indicate that intestinal viruses may be implicated in the establishment of gut microbiota. Therefore, virome analyses should be included in gut microbiota studies to determine the roles of phages and other viruses-such as Chlorella viruses-in human health and disease, particularly during RCDI.}, }
@article {pmid27143392, year = {2016}, author = {Antonopoulos, DA and Chang, EB}, title = {Transplanting a Microbial Organ: the Good, the Bad, and the Unknown.}, journal = {mBio}, volume = {7}, number = {3}, pages = {}, pmid = {27143392}, issn = {2150-7511}, support = {R01 DK047722/DK/NIDDK NIH HHS/United States ; R37 DK047722/DK/NIDDK NIH HHS/United States ; P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DK097268/DK/NIDDK NIH HHS/United States ; }, mesh = {Clostridioides difficile ; Clostridium Infections/*microbiology ; Dysbiosis ; Feces/*microbiology ; Humans ; Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) has received increased attention as a therapy for correcting intestinal dysbiosis and restoring a state of health in patients suffering from either recalcitrant infection by Clostridium difficile or more complex disease states, such as inflammatory bowel disease (IBD). The "gut microbial organ" from the donor that is used in these transplants may serve to transfer genetic material between donor and recipient via virus-like particles, specifically bacteriophages, that infect the bacterial component of the microbiota. The recently published study by Chehoud et al. provides evidence for not only the transfer of bacteriophages during FMT but also the transfer of multiple populations of bacteriophages to recipients from the donor microbiota used (C. Chehoud et al., mBio 7:e00322-16, 2016, http://dx.doi.org/10.1128/mBio.00322-16). While the clinical significance of these findings remains unclear, nothing short of a diligent and persistent effort is needed to define the intended and unintended consequences of FMT.}, }
@article {pmid27143316, year = {2016}, author = {Young, VB and Hayden, MK}, title = {Environmental management in the gut: fecal transplantation to restore the intestinal ecosystem.}, journal = {Infectious diseases (London, England)}, volume = {48}, number = {8}, pages = {593-595}, pmid = {27143316}, issn = {2374-4243}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; U54 CK000161/CK/NCEZID CDC HHS/United States ; U54 CK000481/CK/NCEZID CDC HHS/United States ; }, mesh = {Biomedical Research ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid27142181, year = {2016}, author = {Galloway-Peña, JR and Smith, DP and Sahasrabhojane, P and Ajami, NJ and Wadsworth, WD and Daver, NG and Chemaly, RF and Marsh, L and Ghantoji, SS and Pemmaraju, N and Garcia-Manero, G and Rezvani, K and Alousi, AM and Wargo, JA and Shpall, EJ and Futreal, PA and Guindani, M and Petrosino, JF and Kontoyiannis, DP and Shelburne, SA}, title = {The role of the gastrointestinal microbiome in infectious complications during induction chemotherapy for acute myeloid leukemia.}, journal = {Cancer}, volume = {122}, number = {14}, pages = {2186-2196}, pmid = {27142181}, issn = {1097-0142}, support = {L30 CA209245/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; T32 CA096520/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biodiversity ; Female ; *Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Humans ; Induction Chemotherapy/*adverse effects ; Infections/diagnosis/*etiology ; Leukemia, Myeloid, Acute/*complications/drug therapy ; Male ; Metagenome ; Metagenomics/methods ; Middle Aged ; Prognosis ; RNA, Ribosomal, 16S/genetics ; Young Adult ; }, abstract = {BACKGROUND: Despite increasing data on the impact of the microbiome on cancer, the dynamics and role of the microbiome in infection during therapy for acute myelogenous leukemia (AML) are unknown. Therefore, the authors sought to determine correlations between microbiome composition and infectious outcomes in patients with AML who were receiving induction chemotherapy (IC).<br><br>METHODS: Buccal and fecal specimens (478 samples) were collected twice weekly from 34 patients with AML who were undergoing IC. Oral and stool microbiomes were characterized by 16S ribosomal RNA V4 sequencing using an Illumina MiSeq system. Microbial diversity and genera composition were associated with clinical outcomes.<br><br>RESULTS: Baseline stool &#x3b1;-diversity was significantly lower in patients who developed infections during IC compared with those who did not (P = .047). Significant decreases in both oral and stool microbial &#x3b1;-diversity were observed over the course of IC, with a linear correlation between &#x3b1;-diversity change at the 2 sites (P = .02). Loss of both oral and stool &#x3b1;-diversity was associated significantly with the receipt of a carbapenem P&#x2009;<&#x2009;0.001. Domination events by the majority of genera were transient (median duration, 1 sample), whereas the number of domination events by pathogenic genera increased significantly over the course of IC (P = .002). Moreover, patients who lost microbial diversity over the course of IC were significantly more likely to contract a microbiologically documented infection within the 90 days after IC neutrophil recovery (P = .04).<br><br>CONCLUSIONS: The current data present the largest longitudinal analyses to date of oral and stool microbiomes in patients with AML and suggest that microbiome measurements could assist with the mitigation of infectious complications of AML therapy. Cancer 2016;122:2186-96. &#xa9; 2016 American Cancer Society.}, }
@article {pmid27138569, year = {2016}, author = {Pernot, S and Ramtohul, T and Taieb, J}, title = {Checkpoint inhibitors and gastrointestinal immune-related adverse events.}, journal = {Current opinion in oncology}, volume = {28}, number = {4}, pages = {264-268}, doi = {10.1097/CCO.0000000000000292}, pmid = {27138569}, issn = {1531-703X}, mesh = {Animals ; Antibodies, Monoclonal/*adverse effects/therapeutic use ; Antineoplastic Agents/adverse effects/therapeutic use ; CTLA-4 Antigen/*antagonists &amp; inhibitors/immunology ; Colitis/chemically induced/immunology ; Gastrointestinal Diseases/*chemically induced/immunology ; Humans ; Neoplasms/drug therapy/immunology ; }, abstract = {PURPOSE OF REVIEW: Recent development of checkpoint inhibitors is a challenge for oncologists. Indeed, it leads to specific immune adverse events, close to autoimmune disorders, which require a specific management. Colitis is one of the most frequent immune adverse events, in particular with anticytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy.<br><br>RECENT FINDINGS: Severe colitis is frequent with immune checkpoint inhibitors and leads in a few cases to bowel perforation and death. This review focuses on specific pathogenic pathway and recent findings on risk factors and managements of colitis.<br><br>SUMMARY: Anti-CTLA-4 antibodies are the most involved immune checkpoint inhibitors in colitis, and the combinations with anti-programmed death ligand 1 dramatically increase the rate of colitis. The early use of budesonide, and in some cases corticosteroids and/or infliximab should be recommended, as colitis is responsive to infliximab in almost all cases. Immune-related colitis shares some characteristics with inflammatory bowel disease but with little specificity. In particular, it has been recently showed that gut microbiota could interact with anti-CTLA-4 treatment to modulate efficacy but also to induce colitis. This opens the way for preventive or curative treatments capable of inducing modulation of the microbiota or fecal transplantation.}, }
@article {pmid27137897, year = {2016}, author = {Chilloux, J and Neves, AL and Boulangé, CL and Dumas, ME}, title = {The microbial-mammalian metabolic axis: a critical symbiotic relationship.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {19}, number = {4}, pages = {250-256}, pmid = {27137897}, issn = {1473-6519}, support = {MR/M501797/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animal Nutritional Physiological Phenomena ; Animals ; Diet/adverse effects ; *Diet, Healthy/veterinary ; Dysbiosis/etiology/microbiology/*prevention &amp; control/veterinary ; Fermentation ; *Gastrointestinal Microbiome ; Humans ; Mammals ; Metabolic Diseases/etiology/microbiology/*prevention &amp; control/veterinary ; Prebiotics ; Probiotics ; *Symbiosis ; }, abstract = {PURPOSE OF REVIEW: The microbial-mammalian symbiosis plays a critical role in metabolic health. Microbial metabolites emerge as key messengers in the complex communication between the gut microbiota and their host. These chemical signals are mainly derived from nutritional precursors, which in turn are also able to modify gut microbiota population. Recent advances in the characterization of the gut microbiome and the mechanisms involved in this symbiosis allow the development of nutritional interventions. This review covers the latest findings on the microbial-mammalian metabolic axis as a critical symbiotic relationship particularly relevant to clinical nutrition.<br><br>RECENT FINDINGS: The modulation of host metabolism by metabolites derived from the gut microbiota highlights the importance of gut microbiota in disease prevention and causation. The composition of microbial populations in our gut ecosystem is a critical pathophysiological factor, mainly regulated by diet, but also by the host's characteristics (e.g. genetics, circadian clock, immune system, age). Tailored interventions, including dietary changes, the use of antibiotics, prebiotic and probiotic supplementation and faecal transplantation are promising strategies to manipulate microbial ecology.<br><br>SUMMARY: The microbiome is now considered as an easily reachable target to prevent and treat related diseases. Recent findings in both mechanisms of its interactions with host metabolism and in strategies to modify gut microbiota will allow us to develop more effective treatments especially in metabolic diseases.}, }
@article {pmid27137789, year = {2016}, author = {Fu, N and Wong, T}, title = {Clostridium difficile Infection in Patients with Inflammatory Bowel Disease.}, journal = {Current infectious disease reports}, volume = {18}, number = {6}, pages = {19}, pmid = {27137789}, issn = {1523-3847}, abstract = {Clostridium difficile infection (CDI) is now the leading cause of nosocomial infection. There has been an upsurge of CDI in patients with inflammatory bowel disease (IBD). IBD patients with CDI have increased morbidity and mortality. The establishment, proliferation, and recurrence of CDI in IBD patients form a complex interplay of microbial, environmental, and host-susceptibility factors. Different risk factors have been found predisposing IBD patients to CDI. Vancomycin performs better than metronidazole in treating IBD patients with CDI. Fecal microbiota transplantation continues to be a very effective therapy. New therapeutic modalities such as vaccinations and bile salts are currently being investigated.}, }
@article {pmid27134658, year = {2016}, author = {Tauxe, WM and Haydek, JP and Rebolledo, PA and Neish, E and Newman, KL and Ward, A and Dhere, T and Kraft, CS}, title = {Fecal microbiota transplant for Clostridium difficile infection in older adults.}, journal = {Therapeutic advances in gastroenterology}, volume = {9}, number = {3}, pages = {273-281}, pmid = {27134658}, issn = {1756-283X}, support = {F30 DK100097/DK/NIDDK NIH HHS/United States ; T32 AI074492/AI/NIAID NIH HHS/United States ; T32 GM008169/GM/NIGMS NIH HHS/United States ; UL1 TR000454/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: The objective of this study was to describe the safety of fecal microbiota transplant (FMT) for Clostridium difficile infection (CDI) among older adults.<br><br>METHODS: We performed a case review of all FMT recipients aged 65 or older treated at Emory University Hospital, a tertiary care and referral center for Georgia and surrounding states.<br><br>RESULTS: CDI resolved in 27 (87%) of 31 respondents, including three individuals who received multiple FMTs. Among four whose CDI was not resolved at follow up, three respondents did well initially before CDI recurred, and one individual never eradicated his CDI despite repeating FMT. During the study, five deaths and eight serious adverse events requiring hospitalization were reported within the study group during the follow-up period. Fecal transplant was not a causative factor in these events. The most common adverse event reported in 4 (13%) of 31 respondents was subjective worsening of arthritis.<br><br>CONCLUSION: FMT is a generally safe and effective treatment option for older adults with CDI.}, }
@article {pmid27133778, year = {2016}, author = {Grady, NG and Petrof, EO and Claud, EC}, title = {Microbial therapeutic interventions.}, journal = {Seminars in fetal &amp; neonatal medicine}, volume = {21}, number = {6}, pages = {418-423}, pmid = {27133778}, issn = {1878-0946}, support = {R01 HD083481/HD/NICHD NIH HHS/United States ; }, mesh = {*Dietary Supplements ; *Fecal Microbiota Transplantation ; Humans ; *Microbiota ; *Prebiotics ; *Probiotics ; }, abstract = {The microbiome comprises all the microbes living in and on the human body. Human cells are greatly outnumbered by bacterial cells; thus human health depends on the health of the microbial ecosystem. For the immature preterm infant, the microbiome also influences intestinal and immune system development. This has implications for short term morbidities such as neonatal necrotizing enterocolitis and sepsis, but also long term health outcomes. Optimization of the preterm infant microbiome is a growing topic of interest. The microbial world is not one of good versus evil, but rather one of community; thus optimization includes not only minimizing pathogens, but also enhancing beneficial organisms. Options for optimization include judicious antibiotic use, administration of supplements such as prebiotics or probiotics, and transfaunation procedures such as fecal microbial transplant or microbial ecosystem therapeutics. Potential for benefit as well as risk for each of these options will be discussed.}, }
@article {pmid27129691, year = {2017}, author = {Al Khodor, S and Shatat, IF}, title = {Gut microbiome and kidney disease: a bidirectional relationship.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {32}, number = {6}, pages = {921-931}, pmid = {27129691}, issn = {1432-198X}, mesh = {Carbon/therapeutic use ; Child ; Dietary Supplements ; Disease Progression ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Hypertension/*physiopathology ; Indican/toxicity ; Indoles/metabolism ; Oxides/therapeutic use ; Renal Dialysis ; Renal Insufficiency, Chronic/*physiopathology/*therapy ; }, abstract = {Recent technological advances and efforts, including powerful metagenomic and metatranscriptomic analyses, have led to a tremendous growth in our understanding of microbial communities. Changes in microbial abundance or composition of human microbial communities impact human health or disease state. However, explorations into the mechanisms underlying host-microbe interactions in health and disease are still in their infancy. Although changes in the gut microbiota have been described in patients with kidney disease, the relationships between pathogenesis, mechanisms of disease progression, and the gut microbiome are still evolving. Here, we review changes in the host-microbiome symbiotic relationship in an attempt to explore the bidirectional relationship in which alterations in the microbiome affect kidney disease progression and how kidney disease may disrupt a balanced microbiome. We also discuss potential targeted interventions that may help re-establish this symbiosis and propose more effective ways to deploy traditional treatments in patients with kidney disease.}, }
@article {pmid27127501, year = {2016}, author = {Gweon, TG and Kim, J and Lim, CH and Park, JM and Lee, DG and Lee, IS and Cho, YS and Kim, SW and Choi, MG}, title = {Fecal Microbiota Transplantation Using Upper Gastrointestinal Tract for the Treatment of Refractory or Severe Complicated Clostridium difficile Infection in Elderly Patients in Poor Medical Condition: The First Study in an Asian Country.}, journal = {Gastroenterology research and practice}, volume = {2016}, number = {}, pages = {2687605}, pmid = {27127501}, issn = {1687-6121}, abstract = {Background and Aims. Fecal microbiota transplantation (FMT) is a highly effective treatment option for refractory Clostridium difficile infection (CDI). FMT may be challenging in patients with a low performance status, because of their poor medical condition. The aims of this study were to describe our experience treating patients in poor medical condition with refractory or severe complicated CDI using FMT via the upper GI tract route. Methods. This study was a retrospective review of seven elderly patients with refractory or severe complicated CDI and a poor medical condition who were treated with FMT through the upper GI tract route from May 2012 through August 2013. The outcomes studied included the cure rate of CDI and adverse events. Results. Of these seven patients who received FMT via the upper GI tract route, all patients were cured. During the 11-month follow-up period, CDI recurrence was observed in two patients; rescue FMT was performed in these patients, which led to a full cure. Vomiting was observed in two patients. Conclusions. FMT via the upper gastrointestinal tract route may be effective for the treatment of refractory or severe complicated CDI in patients with a low performance status. Physicians should be aware of adverse events, especially vomiting.}, }
@article {pmid27126044, year = {2016}, author = {Li, SS and Zhu, A and Benes, V and Costea, PI and Hercog, R and Hildebrand, F and Huerta-Cepas, J and Nieuwdorp, M and Salojärvi, J and Voigt, AY and Zeller, G and Sunagawa, S and de Vos, WM and Bork, P}, title = {Durable coexistence of donor and recipient strains after fecal microbiota transplantation.}, journal = {Science (New York, N.Y.)}, volume = {352}, number = {6285}, pages = {586-589}, doi = {10.1126/science.aad8852}, pmid = {27126044}, issn = {1095-9203}, mesh = {Bacteria/classification/isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Symbiosis ; Tissue Donors ; Transplantation, Homologous ; }, abstract = {Fecal microbiota transplantation (FMT) has shown efficacy in treating recurrent Clostridium difficile infection and is increasingly being applied to other gastrointestinal disorders, yet the fate of native and introduced microbial strains remains largely unknown. To quantify the extent of donor microbiota colonization, we monitored strain populations in fecal samples from a recent FMT study on metabolic syndrome patients using single-nucleotide variants in metagenomes. We found extensive coexistence of donor and recipient strains, persisting 3 months after treatment. Colonization success was greater for conspecific strains than for new species, the latter falling within fluctuation levels observed in healthy individuals over a similar time frame. Furthermore, same-donor recipients displayed varying degrees of microbiota transfer, indicating individual patterns of microbiome resistance and donor-recipient compatibilities.}, }
@article {pmid27121964, year = {2016}, author = {Montassier, E and Al-Ghalith, GA and Ward, T and Corvec, S and Gastinne, T and Potel, G and Moreau, P and de la Cochetiere, MF and Batard, E and Knights, D}, title = {Pretreatment gut microbiome predicts chemotherapy-related bloodstream infection.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {49}, pmid = {27121964}, issn = {1756-994X}, support = {UL1 TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Antineoplastic Agents/administration &amp; dosage/adverse effects ; Bacteremia/diagnosis/*epidemiology ; Bacteria/*classification/genetics ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Genetic Variation ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Lymphoma, Non-Hodgkin/microbiology/therapy ; Machine Learning ; Male ; Middle Aged ; RNA, Ribosomal, 16S/analysis ; Retrospective Studies ; Risk Factors ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: Bacteremia, or bloodstream infection (BSI), is a leading cause of death among patients with certain types of cancer. A previous study reported that intestinal domination, defined as occupation of at least 30 % of the microbiota by a single bacterial taxon, is associated with BSI in patients undergoing allo-HSCT. However, the impact of the intestinal microbiome before treatment initiation on the risk of subsequent BSI remains unclear. Our objective was to characterize the fecal microbiome collected before treatment to identify microbes that predict the risk of BSI.<br><br>METHODS: We sampled 28 patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic stem cell transplantation (HSCT) prior to administration of chemotherapy and characterized 16S ribosomal RNA genes using high-throughput DNA sequencing. We quantified bacterial taxa and used techniques from machine learning to identify microbial biomarkers that predicted subsequent BSI.<br><br>RESULTS: We found that patients who developed subsequent BSI exhibited decreased overall diversity and decreased abundance of taxa including Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella. Using machine-learning methods, we developed a BSI risk index capable of predicting BSI incidence with a sensitivity of 90 % at a specificity of 90 % based only on the pretreatment fecal microbiome.<br><br>CONCLUSIONS: These results suggest that the gut microbiota can identify high-risk patients before HSCT and that manipulation of the gut microbiota for prevention of BSI in high-risk patients may be a useful direction for future research. This approach may inspire the development of similar microbiome-based diagnostic and prognostic models in other diseases.}, }
@article {pmid27121861, year = {2016}, author = {Seekatz, AM and Rao, K and Santhosh, K and Young, VB}, title = {Dynamics of the fecal microbiome in patients with recurrent and nonrecurrent Clostridium difficile infection.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {47}, pmid = {27121861}, issn = {1756-994X}, support = {P30 AG024824/AG/NIA NIH HHS/United States ; R21 AI120599/AI/NIAID NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; UL1 TR000433/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteria/*classification/genetics/isolation &amp; purification ; Biodiversity ; Clostridium Infections/*diagnosis/*microbiology ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; RNA, Ribosomal, 16S/*genetics ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (CDI) remains problematic, with up to 30 % of individuals diagnosed with primary CDI experiencing at least one episode of recurrence. The success of microbial-based therapeutics, such as fecal microbiota transplantation, for the treatment of recurrent CDI underscores the importance of restoring the microbiota. However, few studies have looked at the microbial factors that contribute to the development of recurrent disease. Here we compare microbial changes over time in patients with or without recurrence to identify microbial signatures associated with the development of recurrence.<br><br>METHODS: We used 16S rRNA-encoding gene sequence analysis to compare the fecal microbiota of 93 patients with recurrent and nonrecurrent CDI, sampled longitudinally. Cross-group and intra-individual differences in microbial community diversity and similarity were compared prior to the development of recurrent disease and over time.<br><br>RESULTS: Samples from these patient groups exhibited variable community profiles, clustering into four distinct community groups. Cross-group comparison of the index sample collected from patients that did or did not develop recurrence revealed differences in diversity and community structure (analysis of molecular variance, p&#x2009;<&#x2009;0.05). Intra-individual comparisons of the microbiota were more informative and samples from recurrent patients were less likely to recover in diversity (Chi-square test, p&#x2009;<&#x2009;0.005), exhibiting less community similarity overall (Kruskal-Wallis test, p&#x2009;<&#x2009;0.05). Interestingly, patients with severe disease harbored a significantly less diverse community, a trend that was observed across both nonrecurrent and recurrent patient groups (Wilcoxon test, p&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: To date, this study represents one of the largest studies focused on the relationship between predictive signals from the gut microbiota and the development of recurrent CDI. Our data demonstrate that specific microbiota-derived characteristics associate with disease severity and recurrence and that future studies could incorporate these characteristics into predictive models.}, }
@article {pmid27120571, year = {2016}, author = {Rao, K and Higgins, PD}, title = {Epidemiology, Diagnosis, and Management of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {22}, number = {7}, pages = {1744-1754}, pmid = {27120571}, issn = {1536-4844}, support = {P30 AG024824/AG/NIA NIH HHS/United States ; R01 GM097117/GM/NIGMS NIH HHS/United States ; R21 AI120599/AI/NIAID NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/complications/*diagnosis/epidemiology/*therapy ; Fecal Microbiota Transplantation/adverse effects ; Humans ; Immunotherapy ; Inflammatory Bowel Diseases/complications/*diagnosis/drug therapy ; Probiotics/therapeutic use ; Recurrence ; Severity of Illness Index ; Symptom Flare Up ; }, abstract = {Clostridium difficile infection (CDI) is a major source of morbidity and mortality for the U.S. health care system and frequently complicates the course of inflammatory bowel disease (IBD). Patients with IBD are more likely to be colonized with C. difficile and develop active infection than the general population. They are also more likely to have severe CDI and develop subsequent complications such as IBD flare, colectomy, or death. Even after successful initial treatment and recovery, recurrent CDI is common. Management of CDI in IBD is fraught with diagnostic and therapeutic challenges because the clinical presentations of CDI and IBD flare have considerable overlap. Fecal microbiota transplantation can be successful in curing recurrent CDI when other treatments have failed, but may also trigger IBD flare and this warrants caution. New experimental treatments including vaccines, monoclonal antibodies, and nontoxigenic strains of C. difficile offer promise but are not yet available for clinicians. A better understanding of the complex relationship between the gut microbiota, CDI, and IBD is needed.}, }
@article {pmid27114103, year = {2016}, author = {Hummel, B and Hardt, J and Bischofberger, S and Hetzer, F and Warschkow, R and Zadnikar, M and Brunner, W and Widmann, B and Schmied, B and Marti, L}, title = {New kid on the block: perineal stapled prolapse resection (PSP) is it worthwhile in the long-term?.}, journal = {Langenbeck's archives of surgery}, volume = {401}, number = {4}, pages = {519-529}, pmid = {27114103}, issn = {1435-2451}, mesh = {Adult ; Aged ; Aged, 80 and over ; Disease-Free Survival ; Female ; Humans ; Length of Stay ; Male ; Middle Aged ; Operative Time ; Perineum/surgery ; Quality of Life ; Rectal Prolapse/*surgery ; Recurrence ; Retrospective Studies ; Risk Factors ; *Surgical Stapling ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE: Perineal stapled prolapse resection (PSP) has been described as a new surgical treatment for external rectal prolapse in 2008. Short-term and midterm results acknowledged PSP as a safe, fast and simple procedure for high-risk patients. This study aims to assess long-term results after PSP.<br><br>METHODS: All patients who underwent PSP from 2007 to 2015 were analyzed retrospectively. Data was gathered from medical records and operative reports and by interviews with the general practitioner or the patient.<br><br>RESULTS: Indication for PSP was provided in 64 cases. One procedure had to be changed to an Altemeier's and another to a laparoscopic rectopexy. The median age was 79.9&#xa0;years (range 25.9-97.5). Spinal anaesthesia was used in 19 patients. The median operation time was 32.5&#xa0;min (range 25-51.2). There was no mortality. One patient had to be reoperated. All other complications were minor. The median hospital stay was 6.0&#xa0;days (range 2-23). Median follow-up of patients alive was 6.0&#xa0;years (range 0.2-8.4). The 5-year recurrence-free survival rate for primary prolapse was 70.1&#xa0;% compared to 34.3&#xa0;% for recurrent prolapses (p&#x2009;=&#x2009;0.048). Further positive prognostic factors were specimen length over 8&#xa0;cm and lack of preoperative obstructed defecation syndrome. Faecal incontinence was remedied in 18, and new onset was recorded in 6 patients (significant incontinence rate reduction (p&#x2009;=&#x2009;0.025)).<br><br>CONCLUSION: Due to low morbidity and the possibility of spinal anaesthesia, PSP is suitable for frail patients. The recurrence rate for primary prolapse is similar to alternative perineal procedures like Delorme's and Altemeier's, but inferior to the laparoscopic techniques.}, }
@article {pmid27109986, year = {2016}, author = {Galvao, FH and Araki, J and Seid, VE and Waisberg, DR and Traldi, MC and Naito, M and Araujo, BC and Lanchotte, C and Chaib, E and D'Albuquerque, LA}, title = {Evidence That Anorectal Transplantation Is the Logical Treatment for Serious Anorectal Dysfunction and Permanent Colostomy.}, journal = {Transplantation proceedings}, volume = {48}, number = {2}, pages = {497-498}, doi = {10.1016/j.transproceed.2015.10.082}, pmid = {27109986}, issn = {1873-2623}, mesh = {Animals ; *Colostomy ; Dogs ; Fecal Incontinence/*surgery ; Humans ; Quality of Life ; Rats ; Recovery of Function ; Rectum/*transplantation ; Swine ; }, abstract = {Anorectal dysfunction resulting in fecal incontinence or permanent colostomy is a current public health concern that strongly impairs patient quality of life. Present treatment options for this complex disease are expensive and usually ineffective. Anorectal transplantation is the logical treatment for fecal incontinence and permanent colostomy. This procedure has been clinically effective in a few cases reported in the medical literature. Furthermore, experiments in rats, pigs, and dogs have shown promising results, with functional recovery of the graft. In this article we describe the scientific evidence that anorectal transplantation may be an important option for treating anorectal dysfunction.}, }
@article {pmid27109966, year = {2016}, author = {Scaldaferri, F and Pecere, S and Petito, V and Zambrano, D and Fiore, L and Lopetuso, LR and Schiavoni, E and Bruno, G and Gerardi, V and Laterza, L and Pizzoferrato, M and Ianiro, G and Stojanovic, J and Poscia, A and Papa, A and Paroni Sterbini, F and Sanguinetti, M and Masucci, L and Cammarota, G and Gasbarrini, A}, title = {Efficacy and Mechanisms of Action of Fecal Microbiota Transplantation in Ulcerative Colitis: Pitfalls and Promises From a First Meta-Analysis.}, journal = {Transplantation proceedings}, volume = {48}, number = {2}, pages = {402-407}, doi = {10.1016/j.transproceed.2015.12.040}, pmid = {27109966}, issn = {1873-2623}, mesh = {Colitis, Ulcerative/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is the results of a chronic inflammatory process deriving from disequilibrium between self-microbiota composition and immune response.<br><br>METHODS: New evidence, coming from Clostridium difficile infection, clearly showed that active and powerful modulation of microbiota composition by fecal microbiota composition (FMT) is safe, easy to perform, and efficacious, opening new frontiers in gastrointestinal and extra-intestinal diseases. FMT has been proposed also for IBD as well as other non-gastrointestinal conditions related to intestinal microbiota dysfunctions, with good preliminary data.<br><br>RESULTS: In this setting, ulcerative colitis (UC) represents one of the most robust potential indications for FMT after C difficile colitis.<br><br>CONCLUSIONS: In the present review, we focus on FMT and its application on ulcerative colitis, clarifying mechanisms of actions and efficacy data, trough completion of a meta-analysis on&#xa0;available randomized, controlled trial data in UC. Because microbiota is so crucially involved in this topic, a short review of microbial alterations in UC will also be performed.}, }
@article {pmid27104515, year = {2016}, author = {Matijašić, M and Meštrović, T and Perić, M and Čipčić Paljetak, H and Panek, M and Vranešić Bender, D and Ljubas Kelečić, D and Krznarić, &#x17d; and Verbanac, D}, title = {Modulating Composition and Metabolic Activity of the Gut Microbiota in IBD Patients.}, journal = {International journal of molecular sciences}, volume = {17}, number = {4}, pages = {}, pmid = {27104515}, issn = {1422-0067}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; *Diet ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Helminths/physiology ; Homeostasis ; Humans ; Inflammatory Bowel Diseases/*microbiology/parasitology/therapy ; Nutritional Physiological Phenomena ; Prebiotics ; Probiotics/therapeutic use ; Synbiotics ; }, abstract = {The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gut microbiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce. In this review we present and discuss currently available and emerging therapeutic options in modulating composition and metabolic activity of gut microbiota in patients affected by IBD. Therapeutic approaches at the microbiota level, such as dietary interventions alone or with probiotics, prebiotics and synbiotics, administration of antibiotics, performing fecal microbiota transplantation (FMT) and the use of nematodes, all represent a promising opportunities towards establishing and maintaining of well-being as well as improving underlying IBD symptoms.}, }
@article {pmid27104013, year = {2016}, author = {Jeon, YD and Hong, N and Kim, JH and Park, SH and Kim, SB and Song, IJ and Ann, HW and Ahn, JY and Kim, SB and Ku, NS and Lee, K and Yong, D and Kim, JM and Choi, JY}, title = {Fecal Transplantation using a Nasoenteric Tube during an Initial Episode of Severe Clostridium difficile Infection.}, journal = {Infection &amp; chemotherapy}, volume = {48}, number = {1}, pages = {31-35}, pmid = {27104013}, issn = {2093-2340}, abstract = {The incidence of Clostridium difficile infection is increasing worldwide, and its severity and resulting mortality are also on the rise. Metronidazole and oral vancomycin remain the treatments of choice, but there are concerns about treatment failure and the appearance of resistant strains. Furthermore, antibiotic therapy results in recurrence rates of at least 20%. Fecal transplantation may be a feasible treatment option for recurrent C. difficile infection; moreover, it may be an early treatment option for severe C. difficile infection. We report a case of severe C. difficile infection treated with fecal transplantation using a nasoenteric tube during an initial episode. This is the first reported case of fecal transplantation using a nasoenteric tube during an initial episode of C. difficile infection in Korea.}, }
@article {pmid27102140, year = {2016}, author = {Raoult, D}, title = {The return of microbes.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {22}, number = {10}, pages = {822-823}, doi = {10.1016/j.cmi.2016.04.006}, pmid = {27102140}, issn = {1469-0691}, mesh = {Animals ; Humans ; *Microbiota ; Neoplasms/prevention &amp; control/therapy ; Preventive Medicine ; Probiotics/adverse effects/*therapeutic use ; Weight Gain ; }, }
@article {pmid27096607, year = {2016}, author = {Tourret, J and Willing, BP and Croxen, MA and Dufour, N and Dion, S and Wachtel, S and Denamur, E and Finlay, BB}, title = {Small Intestine Early Innate Immunity Response during Intestinal Colonization by Escherichia coli Depends on Its Extra-Intestinal Virulence Status.}, journal = {PloS one}, volume = {11}, number = {4}, pages = {e0153034}, pmid = {27096607}, issn = {1932-6203}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Enterobacteriaceae/immunology ; Enterobacteriaceae Infections/immunology/microbiology ; Escherichia coli Infections/*immunology/microbiology ; Humans ; *Immunity, Innate ; Interleukin-10/immunology ; Interleukin-6/immunology ; Intestine, Small/*immunology/*microbiology ; Mice ; Mice, Inbred C57BL ; Tumor Necrosis Factor-alpha/immunology ; Urinary Tract Infections/*immunology/microbiology ; Uropathogenic Escherichia coli/*immunology ; }, abstract = {Uropathogenic Escherichia coli (UPEC) strains live as commensals in the digestive tract of the host, but they can also initiate urinary tract infections. The aim of this work was to determine how a host detects the presence of a new UPEC strain in the digestive tract. Mice were orally challenged with UPEC strains 536 and CFT073, non-pathogenic strain K12 MG1655, and ΔPAI-536, an isogenic mutant of strain 536 lacking all 7 pathogenicity islands whose virulence is drastically attenuated. Intestinal colonization was measured, and cytokine expression was determined in various organs recovered from mice after oral challenge. UPEC strain 536 efficiently colonized the mouse digestive tract, and prior Enterobacteriaceae colonization was found to impact strain 536 colonization efficiency. An innate immune response, detected as the production of TNFα, IL-6 and IL-10 cytokines, was activated in the ileum 48 hours after oral challenge with strain 536, and returned to baseline within 8 days, without a drop in fecal pathogen load. Although inflammation was detected in the ileum, histology was normal at the time of cytokine peak. Comparison of cytokine secretion 48h after oral gavage with E. coli strain 536, CFT073, MG1655 or ΔPAI-536 showed that inflammation was more pronounced with UPECs than with non-pathogenic or attenuated strains. Pathogenicity islands also seemed to be involved in host detection, as IL-6 intestinal secretion was increased after administration of E. coli strain 536, but not after administration of ΔPAI-536. In conclusion, UPEC colonization of the mouse digestive tract activates acute phase inflammatory cytokine secretion but does not trigger any pathological changes, illustrating the opportunistic nature of UPECs. This digestive tract colonization model will be useful for studying the factors controlling the switch from commensalism to pathogenicity.}, }
@article {pmid27093642, year = {2016}, author = {Guo, Y and Qi, Y and Yang, X and Zhao, L and Wen, S and Liu, Y and Tang, L}, title = {Association between Polycystic Ovary Syndrome and Gut Microbiota.}, journal = {PloS one}, volume = {11}, number = {4}, pages = {e0153196}, pmid = {27093642}, issn = {1932-6203}, mesh = {Animals ; Aromatase Inhibitors/pharmacology ; Estrous Cycle/drug effects/physiology ; Female ; Gastrointestinal Microbiome/drug effects/*physiology ; Letrozole ; Microbiota/drug effects ; Nitriles/pharmacology ; Ovary/pathology ; Polycystic Ovary Syndrome/drug therapy/*pathology ; Rats ; Rats, Sprague-Dawley ; Triazoles/pharmacology ; }, abstract = {Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. Here, we characterized the roles of gut microbiota on the pathogenesis and treatments in letrozole (a nonsteroidal aromatase inhibitor) induced PCOS rat model. Changes in estrous cycles, hormonal levels, ovarian morphology and gut microbiota by PCR-DGGE and real-time PCR were determined. The results showed that PCOS rats displayed abnormal estrous cycles with increasing androgen biosynthesis and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Meanwhile, the composition of gut microbiota in letrozole-treated rats was different from that in the controls. Lactobacillus, Ruminococcus and Clostridium were lower while Prevotella was higher in PCOS rats when compared with control rats. After treating PCOS rats with Lactobacillus and fecal microbiota transplantation (FMT) from healthy rats, it was found that the estrous cycles were improved in all 8 rats in FMT group, and in 6 of the 8 rats in Lactobacillus transplantation group with decreasing androgen biosynthesis. Their ovarian morphologies normalized. The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella. These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS. Microbiota interventions through FMT and Lactobacillus transplantation were beneficial for the treatments of PCOS rats.}, }
@article {pmid27090230, year = {2016}, author = {Nettleton, JE and Reimer, RA and Shearer, J}, title = {Reshaping the gut microbiota: Impact of low calorie sweeteners and the link to insulin resistance?.}, journal = {Physiology &amp; behavior}, volume = {164}, number = {Pt B}, pages = {488-493}, doi = {10.1016/j.physbeh.2016.04.029}, pmid = {27090230}, issn = {1873-507X}, mesh = {Animals ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Insulin Resistance/*physiology ; Non-Nutritive Sweeteners/*administration &amp; dosage/adverse effects/analysis/chemistry ; Obesity/epidemiology/metabolism/microbiology ; }, abstract = {Disruption in the gut microbiota is now recognized as an active contributor towards the development of obesity and insulin resistance. This review considers one class of dietary additives known to influence the gut microbiota that may predispose susceptible individuals to insulin resistance - the regular, long-term consumption of low-dose, low calorie sweeteners. While the data are controversial, mounting evidence suggests that low calorie sweeteners should not be dismissed as inert in the gut environment. Sucralose, aspartame and saccharin, all widely used to reduce energy content in foods and beverages to promote satiety and encourage weight loss, have been shown to disrupt the balance and diversity of gut microbiota. Fecal transplant experiments, wherein microbiota from low calorie sweetener consuming hosts are transferred into germ-free mice, show that this disruption is transferable and results in impaired glucose tolerance, a well-known risk factor towards the development of a number of metabolic disease states. As our understanding of the importance of the gut microbiota in metabolic health continues to grow, it will be increasingly important to consider the impact of all dietary components, including low calorie sweeteners, on gut microbiota and metabolic health.}, }
@article {pmid27088842, year = {2016}, author = {Cordey, S and Vu, DL and Schibler, M and L'Huillier, AG and Brito, F and Docquier, M and Posfay-Barbe, KM and Petty, TJ and Turin, L and Zdobnov, EM and Kaiser, L}, title = {Astrovirus MLB2, a New Gastroenteric Virus Associated with Meningitis and Disseminated Infection.}, journal = {Emerging infectious diseases}, volume = {22}, number = {5}, pages = {846-853}, pmid = {27088842}, issn = {1080-6059}, mesh = {Astroviridae Infections/diagnosis/epidemiology/*virology ; High-Throughput Nucleotide Sequencing ; Humans ; Mamastrovirus/*classification/genetics ; Meningitis, Viral/diagnosis/epidemiology/*virology ; Phylogeny ; Prevalence ; RNA, Viral ; Switzerland/epidemiology ; }, abstract = {Next-generation sequencing has identified novel astroviruses for which a pathogenic role is not clearly defined. We identified astrovirus MLB2 infection in an immunocompetent case-patient and an immunocompromised patient who experienced diverse clinical manifestations, notably, meningitis and disseminated infection. The initial case-patient was identified by next-generation sequencing, which revealed astrovirus MLB2 RNA in cerebrospinal fluid, plasma, urine, and anal swab specimens. We then used specific real-time reverse transcription PCR to screen 943 fecal and 424 cerebrospinal fluid samples from hospitalized patients and identified a second case of meningitis, with positive results for the agent in the patient's feces and plasma. This screening revealed 5 additional positive fecal samples: 1 from an infant with acute diarrhea and 4 from children who had received transplants. Our findings demonstrate that astrovirus MLB2, which is highly prevalent in feces, can disseminate outside the digestive tract and is an unrecognized cause of central nervous system infection.}, }
@article {pmid27086820, year = {2016}, author = {Tanaka, T and Kato, H and Fujimoto, T}, title = {Successful Fecal Microbiota Transplantation as an Initial Therapy for Clostridium difficile Infection on an Outpatient Basis.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {55}, number = {8}, pages = {999-1000}, doi = {10.2169/internalmedicine.55.5701}, pmid = {27086820}, issn = {1349-7235}, mesh = {Clostridioides difficile ; Clostridium Infections/*therapy ; Colonoscopy/methods ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome ; Humans ; Middle Aged ; *Outpatients ; Recurrence ; }, abstract = {A 64-year-old woman developed diarrhea after taking clindamycin for a dental infection. We diagnosed her with Clostridium difficile infection (CDI) and performed fecal microbiota transplantation (FMT) as the initial therapy using colonoscopy on an outpatient basis. The frequency of her bowel movements decreased from 10 times per day to two times per day three days after the procedure. The key component of FMT is to restructure the protective microbiome of the natural intestinal flora. We consider that FMT could be used as an effective first-line therapy for CDI if the efficacy and safety of this procedure is established in the future.}, }
@article {pmid27085375, year = {2016}, author = {Pessatti, TB and Lüchmann, KH and Flores-Nunes, F and Mattos, JJ and Sasaki, ST and Taniguchi, S and Bícego, MC and Dias Bainy, AC}, title = {Upregulation of biotransformation genes in gills of oyster Crassostrea brasiliana exposed in situ to urban effluents, Florianópolis Bay, Southern Brazil.}, journal = {Ecotoxicology and environmental safety}, volume = {131}, number = {}, pages = {172-180}, doi = {10.1016/j.ecoenv.2016.04.003}, pmid = {27085375}, issn = {1090-2414}, mesh = {Animals ; Bays ; Biotransformation/drug effects ; Brazil ; Crassostrea/*drug effects ; Cytochrome P-450 Enzyme System/drug effects/genetics ; Environmental Monitoring/methods ; Gills/*drug effects ; Glutathione Transferase/metabolism ; Isoenzymes/metabolism ; Sanitation ; Sewage/chemistry ; Transcription, Genetic/drug effects ; Up-Regulation ; Wastewater/toxicity ; Water Pollutants, Chemical/metabolism/*toxicity ; Xenobiotics/metabolism ; }, abstract = {The release of untreated sanitary sewage, combined with unplanned urban growth, are major factors contributing to degradation of coastal ecosystems in developing countries, including Brazil. Sanitary sewage is a complex mixture of chemicals that can negatively affect aquatic organisms. The use of molecular biomarkers can help to understand and to monitor the biological effects elicited by contaminants. The aim of this study was to evaluate changes in transcript levels of genes related to xenobiotic biotransformation in the gills of oysters Crassostrea brasiliana transplanted and kept for 24h at three areas potentially contaminated by sanitary sewage (Bücheller river, BUC; Biguaçu river, BIG; and Ratones island, RAT), one farming area (Sambaqui beach, SAM) and at one reference site (Forte beach, FOR) in the North Bay of Santa Catarina Island (Florianópolis, Brazil). Transcript levels of four cytochrome P450 isoforms (CYP2AU1, CYP3A-like, CYP356A1-like and CYP20A1-like), three glutathione S-transferase (GST alpha-like, GST pi-like and GST microsomal 3-like) and one sulfotransferase gene (SULT-like) were evaluated by means of quantitative reverse transcription PCR (qRT-PCR). Chemical analysis of the sediment from each site were performed and revealed the presence of aliphatic and polycyclic aromatic hydrocarbons, linear alkylbenzenes and fecal sterols in the contaminated areas (BUC and BIG). Water quality analysis showed that these sites had the highest levels of fecal coliforms and other parameters evidencing the presence of urban sewage discharges. Among the results for gene transcription, CYP2AU1 and SULT-like levels were upregulated by 20 and 50-fold, respectively, in the oysters kept for 24h at the most contaminated site (BUC), suggesting a role of these genes in the detoxification of organic pollutants. These data reinforce that gills possibly have an important role in xenobiotic metabolism and highlight the use of C. brasiliana as a sentinel for monitoring environmental contamination in coastal regions.}, }
@article {pmid27075753, year = {2017}, author = {Yoshikawa, K and Kurihara, C and Furuhashi, H and Takajo, T and Maruta, K and Yasutake, Y and Sato, H and Narimatsu, K and Okada, Y and Higashiyama, M and Watanabe, C and Komoto, S and Tomita, K and Nagao, S and Miura, S and Tajiri, H and Hokari, R}, title = {Psychological stress exacerbates NSAID-induced small bowel injury by inducing changes in intestinal microbiota and permeability via glucocorticoid receptor signaling.}, journal = {Journal of gastroenterology}, volume = {52}, number = {1}, pages = {61-71}, pmid = {27075753}, issn = {1435-5922}, mesh = {Animals ; Anti-Inflammatory Agents, Non-Steroidal/administration &amp; dosage/*adverse effects ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Indomethacin/adverse effects ; Intestinal Diseases/*chemically induced/microbiology/pathology ; Intestine, Small/drug effects/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Permeability ; RNA, Messenger/metabolism ; Receptors, Glucocorticoid/metabolism ; Signal Transduction ; Stress, Psychological/*complications ; Tumor Necrosis Factor-alpha/genetics ; }, abstract = {BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are popular painkillers, but they have serious side effects, not only in the upper gastrointestinal tract but also in the small intestine. It is well known that psychological stress may exacerbate various gastrointestinal diseases. The aim of this study was to determine whether psychological stress exacerbates NSAID enteropathy and to determine the possible underlying mechanisms for this.<br><br>METHODS: Experiment 1: mice were exposed to water avoidance stress (WAS) or sham stress for 1&#xa0;h per day for 8 consecutive days, and then enteropathy was induced by indomethacin. Experiment 2: cecal contents from stress (-) or (+) mice were transplanted into mice that had received antibiotics and in which NSAID enteropathy had been induced without WAS. Experiment 3: mifepristone, a glucocorticoid receptor antagonist, was injected before WAS for 8&#xa0;days. Small intestinal injury, mRNA expression of TNF&#x3b1;, intestinal permeability, and the microbial community were assessed.<br><br>RESULTS: Psychological stress exacerbated NSAID enteropathy and increased intestinal permeability. Psychological stress induced changes in the ileal microbiota that were characterized by increases in the total number of bacteria and the proportion of Gram-negative bacteria. The increased susceptibility to NSAIDs and intestinal permeability due to WAS was transferable via cecal microbiota transplantation. The increased permeability and aggravation of NSAID enteropathy caused by WAS were blocked by the administration of mifepristone.<br><br>CONCLUSIONS: This study demonstrated a relationship between NSAID enteropathy and psychological stress, and showed the utility of studying the intestinal microbiota in order to elucidate the pathophysiology of NSAID enteropathy. It also showed the impact of stress on the intestinal microbiota and the mucosal barrier in gastrointestinal diseases.}, }
@article {pmid27074706, year = {2016}, author = {Langdon, A and Crook, N and Dantas, G}, title = {The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {39}, pmid = {27074706}, issn = {1756-994X}, support = {DP2 DK098089/DK/NIDDK NIH HHS/United States ; R01 GM099538/GM/NIGMS NIH HHS/United States ; T32 DK077653/DK/NIDDK NIH HHS/United States ; DP2-DK-098089/DK/NIDDK NIH HHS/United States ; R01-GM099538/GM/NIGMS NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; TL1 TR000449/TR/NCATS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/adverse effects/*pharmacology/*therapeutic use ; Bacterial Infections/*drug therapy/*microbiology ; Disease Susceptibility ; Host-Pathogen Interactions/drug effects ; Humans ; Metagenome ; Metagenomics ; Microbiota/*drug effects ; Risk Factors ; }, abstract = {The widespread use of antibiotics in the past 80 years has saved millions of human lives, facilitated technological progress and killed incalculable numbers of microbes, both pathogenic and commensal. Human-associated microbes perform an array of important functions, and we are now just beginning to understand the ways in which antibiotics have reshaped their ecology and the functional consequences of these changes. Mounting evidence shows that antibiotics influence the function of the immune system, our ability to resist infection, and our capacity for processing food. Therefore, it is now more important than ever to revisit how we use antibiotics. This review summarizes current research on the short-term and long-term consequences of antibiotic use on the human microbiome, from early life to adulthood, and its effect on diseases such as malnutrition, obesity, diabetes, and Clostridium difficile infection. Motivated by the consequences of inappropriate antibiotic use, we explore recent progress in the development of antivirulence approaches for resisting infection while minimizing resistance to therapy. We close the article by discussing probiotics and fecal microbiota transplants, which promise to restore the microbiota after damage of the microbiome. Together, the results of studies in this field emphasize the importance of developing a mechanistic understanding of gut ecology to enable the development of new therapeutic strategies and to rationally limit the use of antibiotic compounds.}, }
@article {pmid27074695, year = {2016}, author = {Russell, RK and Hansen, R and Turner, D}, title = {New treatments for ulcerative colitis: do we have pediatric data?.}, journal = {Expert review of clinical immunology}, volume = {12}, number = {7}, pages = {701-704}, doi = {10.1080/1744666X.2016.1177459}, pmid = {27074695}, issn = {1744-8409}, mesh = {Algorithms ; Antibodies, Monoclonal/*therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Biosimilar Pharmaceuticals/*therapeutic use ; Child ; Clinical Decision-Making ; Colectomy ; Colitis, Ulcerative/immunology/*therapy ; Humans ; Immunotherapy/*methods ; Practice Guidelines as Topic ; Treatment Outcome ; }, }
@article {pmid27067014, year = {2016}, author = {Zheng, P and Zeng, B and Zhou, C and Liu, M and Fang, Z and Xu, X and Zeng, L and Chen, J and Fan, S and Du, X and Zhang, X and Yang, D and Yang, Y and Meng, H and Li, W and Melgiri, ND and Licinio, J and Wei, H and Xie, P}, title = {Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism.}, journal = {Molecular psychiatry}, volume = {21}, number = {6}, pages = {786-796}, pmid = {27067014}, issn = {1476-5578}, mesh = {Animals ; Depression/*metabolism/microbiology ; Depressive Disorder, Major/metabolism/microbiology ; Dysbiosis/metabolism/psychology ; Gastrointestinal Microbiome/*physiology ; Gene-Environment Interaction ; Humans ; Mice ; Microbiota/physiology ; }, abstract = {Major depressive disorder (MDD) is the result of complex gene-environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiology of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clinical sampling, the gut microbiotic compositions of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with 'depression microbiota' derived from MDD patients resulted in depression-like behaviors compared with colonization with 'healthy microbiota' derived from healthy control individuals. Mice harboring 'depression microbiota' primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host's metabolism.}, }
@article {pmid27065726, year = {2016}, author = {Ofosu, A}, title = {Clostridium difficile infection: a review of current and emerging therapies.}, journal = {Annals of gastroenterology}, volume = {29}, number = {2}, pages = {147-154}, pmid = {27065726}, issn = {1108-7471}, abstract = {Clostridium difficile (C. difficile) infection (CDI) is the most common cause of -healthcare-associated infections in US hospitals. The epidemic strain NAP1/BI/ribotype 027 accounts for outbreaks worldwide, with increasing mortality and severity. CDI is acquired from an endogenous source or from spores in the environment, most easily acquired during the hospital stay. The use of antimicrobials disrupts the intestinal microflora enabling C. difficile to proliferate in the colon and produce toxins. Clinical diagnosis in symptomatic patients requires toxin detection from stool specimens and rarely in combination with stool culture to increase sensitivity. However, stool culture is essential for epidemiological studies. Oral metronidazole is the recommended therapy for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases. Treatment of first recurrence involves the use of the same therapy used in the initial CDI. In the event of a second recurrence oral vancomycin often given in a tapered dose or intermittently, or fidaxomicin may be used. Fecal transplantation is playing an immense role in therapy of recurrent CDI with remarkable results. Fulminant colitis and toxic megacolon warrant surgical intervention. Novel approaches including new antibiotics and immunotherapy against CDI or its toxins appear to be of potential value.}, }
@article {pmid27062204, year = {2016}, author = {Trubiano, JA and Cheng, AC and Korman, TM and Roder, C and Campbell, A and May, ML and Blyth, CC and Ferguson, JK and Blackmore, TK and Riley, TV and Athan, E}, title = {Australasian Society of Infectious Diseases updated guidelines for the management of Clostridium difficile infection in adults and children in Australia and New Zealand.}, journal = {Internal medicine journal}, volume = {46}, number = {4}, pages = {479-493}, doi = {10.1111/imj.13027}, pmid = {27062204}, issn = {1445-5994}, mesh = {Adult ; Australasia/epidemiology ; Australia/epidemiology ; *Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/diagnosis/*epidemiology/*therapy ; Communicable Diseases/diagnosis/epidemiology/therapy ; *Disease Management ; Humans ; New Zealand/epidemiology ; Practice Guidelines as Topic/*standards ; Societies, Medical/*standards/trends ; }, abstract = {The incidence of Clostridium difficile infection (CDI) continues to rise, whilst treatment remains problematic due to recurrent, refractory and potentially severe nature of disease. The treatment of C. difficile is a challenge for community and hospital-based clinicians. With the advent of an expanding therapeutic arsenal against C. difficile since the last published Australasian guidelines, an update on CDI treatment recommendations for Australasian clinicians was required. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children.}, }
@article {pmid27058556, year = {2016}, author = {Woting, A and Blaut, M}, title = {The Intestinal Microbiota in Metabolic Disease.}, journal = {Nutrients}, volume = {8}, number = {4}, pages = {202}, pmid = {27058556}, issn = {2072-6643}, mesh = {Adiposity/*physiology ; Animals ; Bacteria/*classification/metabolism ; Diabetes Mellitus, Type 2/*metabolism ; Dyslipidemias/*metabolism ; Fatty Acids, Volatile/metabolism ; Humans ; Intestines/*microbiology ; }, abstract = {Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions.}, }
@article {pmid27058534, year = {2016}, author = {Fröhlich, EE and Fröhlich, E}, title = {Cytotoxicity of Nanoparticles Contained in Food on Intestinal Cells and the Gut Microbiota.}, journal = {International journal of molecular sciences}, volume = {17}, number = {4}, pages = {509}, pmid = {27058534}, issn = {1422-0067}, mesh = {Animals ; Anti-Infective Agents/adverse effects/chemistry/*toxicity ; Cell Survival/drug effects ; Enterocytes/*drug effects ; Gastrointestinal Microbiome/*drug effects ; Humans ; Nanoparticles/adverse effects/chemistry/*toxicity ; Silver/adverse effects/chemistry/*toxicity ; Zinc Oxide/adverse effects/chemistry/*toxicity ; }, abstract = {Toxicity of nanoparticles (NPs) upon oral exposure has been studied in animals using physiological changes, behavior, histology, and blood analysis for evaluation. The effects recorded include the combination of the action on cells of the exposed animal and the reaction of the microorganisms that populate the external and internal surfaces of the body. The importance of these microorganisms, collectively termed as microbiota, for the health of the host has been widely recognized. They may also influence toxicity of NPs but these effects are difficult to differentiate from toxicity on cells of the gastrointestinal tract. To estimate the likelihood of preferential damage of the microbiota by NPs the relative sensitivity of enterocytes and bacteria was compared. For this comparison NPs with antimicrobial action present in consumer products were chosen. The comparison of cytotoxicity with Escherichia coli as representative for intestinal bacteria and on gastrointestinal cells revealed that silver NPs damaged bacteria at lower concentrations than enterocytes, while the opposite was true for zinc oxide NPs. These results indicate that silver NPs may cause adverse effects by selectively affecting the gut microbiota. Fecal transplantation from NP-exposed animals to unexposed ones offers the possibility to verify this hypothesis.}, }
@article {pmid27057686, year = {2016}, author = {Quezada, SM and Briscoe, J and Cross, RK}, title = {Complementary and Alternative Medicine.}, journal = {Inflammatory bowel diseases}, volume = {22}, number = {6}, pages = {1523-1530}, doi = {10.1097/MIB.0000000000000761}, pmid = {27057686}, issn = {1536-4844}, mesh = {Aloe ; Andrographis ; Animals ; Cannabis ; *Complementary Therapies ; Curcumin/therapeutic use ; Fatty Acids, Omega-3/*therapeutic use ; Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*therapy ; Phytotherapy ; Plant Extracts/*therapeutic use ; Plants, Medicinal ; Trichuris/immunology ; Triticum ; }, abstract = {Inflammatory bowel disease is a complex, chronic, multifactorial inflammatory disorder of the digestive tract. Standard therapies include immunosuppressive and biological treatments, but there is increasing interest in the potential benefit of complementary and alternative medicine for the treatment of inflammatory bowel disease. Given the high prevalence of use of complementary and alternative medicine among inflammatory bowel disease patients, gastroenterologists must remain knowledgeable regarding the risks and benefits of these treatment options. This article reviews the updated scientific data on the use of biologically based complementary and alternative therapies for the treatment of inflammatory bowel disease.}, }
@article {pmid27056946, year = {2016}, author = {Teich, N and Weber, M and Stallmach, A}, title = {First Occurrence of Severe Extraintestinal Manifestations of Crohn's Disease Following Faecal Microbiota Transplantation.}, journal = {Journal of Crohn's &amp; colitis}, volume = {10}, number = {10}, pages = {1254-1255}, doi = {10.1093/ecco-jcc/jjw081}, pmid = {27056946}, issn = {1876-4479}, mesh = {Adult ; *Clostridioides difficile ; Clostridium Infections/complications/*therapy ; Crohn Disease/*complications ; Disease Progression ; Erythema Nodosum/diagnosis/*etiology ; Fecal Microbiota Transplantation/*adverse effects ; Female ; Humans ; Opportunistic Infections/complications/*therapy ; }, }
@article {pmid27054442, year = {2016}, author = {Wang, Z and Koonen, D and Hofker, M and Fu, J}, title = {Gut microbiome and lipid metabolism: from associations to mechanisms.}, journal = {Current opinion in lipidology}, volume = {27}, number = {3}, pages = {216-224}, doi = {10.1097/MOL.0000000000000308}, pmid = {27054442}, issn = {1473-6535}, mesh = {Animals ; Diet ; *Gastrointestinal Microbiome ; Humans ; *Lipid Metabolism ; Lipids/blood ; Precision Medicine ; }, abstract = {PURPOSE OF REVIEW: The gut microbiome has now been convincingly linked to human metabolic health but the underlying causality and mechanisms remain poorly understood. This review focuses on the recent progress in establishing the associations between gut microbiome species and lipid metabolism in humans and discusses how to move from association toward causality and mechanistic understanding, which is essential knowledge to bring the observed associations into clinical use.<br><br>RECENT FINDINGS: Recent population-based association studies have shown that the gut microbiota composition can explain a substantial proportion of the interindividual variation in blood triglycerides and HDL-cholesterol level and predict metabolic response to diet and drug. Faecal transplantation has suggested that this is a causal effect of microbiome on host metabolism, although the underlying mechanism remains largely unexplored.<br><br>SUMMARY: The gut microbiome is transitioning from being a 'missing' organ to a potential target for therapeutic applications. Due to the complex interplay between the gut microbiome, the host genome, and diet, a systematic approach is required to pave the way for therapeutic development.}, }
@article {pmid27048904, year = {2016}, author = {Haque, TR and Barritt, AS}, title = {Intestinal microbiota in liver disease.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {30}, number = {1}, pages = {133-142}, doi = {10.1016/j.bpg.2016.02.004}, pmid = {27048904}, issn = {1532-1916}, mesh = {Dysbiosis/physiopathology ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Immune System ; Liver Diseases/microbiology/*physiopathology/prevention &amp; control ; Probiotics/therapeutic use ; }, abstract = {The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation.}, }
@article {pmid27048199, year = {2016}, author = {Zellmer, C and De Wolfe, TJ and Van Hoof, S and Blakney, R and Safdar, N}, title = {Patient Perspectives on Fecal Microbiota Transplantation for Clostridium Difficile Infection.}, journal = {Infectious diseases and therapy}, volume = {5}, number = {2}, pages = {155-164}, pmid = {27048199}, issn = {2193-8229}, abstract = {INTRODUCTION: Clostridium difficile infection (CDI) is a severe and increasingly frequent healthcare-associated infection that develops after disruption of the gut microbiota. Immunocompromised, hospitalized patients have an increased likelihood of acquiring CDI, leading to lengthened hospital stays, increased medical fees, and higher rates of morbidity and mortality. Treatment of CDI is challenging because of limited treatment options and a 19-20% recurrence rate. Thus, there is a need for effective, affordable and safe treatments for CDI. Fecal microbiota transplantation (FMT) is the transplantation of donor stool into the intestine of a CDI patient to restore the structure and function of the gut microbiota and eradicate CDI. Recently, FMT has become an attractive alternative treatment for CDI due to its overwhelming success rate. However, the patient perspective on the effect of CDI and the role of FMT in that context is lacking.<br><br>METHODS: We undertook a patient survey to gather qualitative and quantitative data on the short-term social, physical, emotional outcomes for patients with CDI who have undergone FMT.<br><br>RESULTS: We found in all patients interviewed that the social implications of CDI were generally more severe than the emotional and physical aspects.<br><br>CONCLUSION: Future studies should consider evaluating these important patient-centered factors as outcomes. Moreover, patients are willing to undergo FMT as treatment for CDI.}, }
@article {pmid27045424, year = {2016}, author = {Steinert, A and Radulovic, K and Niess, J}, title = {Gastro-intestinal tract: The leading role of mucosal immunity.}, journal = {Swiss medical weekly}, volume = {146}, number = {}, pages = {w14293}, doi = {10.4414/smw.2016.14293}, pmid = {27045424}, issn = {1424-3997}, mesh = {Amino Acids/metabolism ; Anti-Bacterial Agents/therapeutic use ; Bile Acids and Salts/metabolism ; Enterocolitis, Pseudomembranous/therapy ; Fatty Acids/metabolism ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*immunology ; Gastrointestinal Tract/*immunology/metabolism ; Humans ; Immunity, Mucosal/*immunology ; Inflammatory Bowel Diseases/therapy ; Probiotics/therapeutic use ; Vitamins/metabolism ; }, abstract = {An understanding of mucosal immunity is essential for the comprehension of intestinal diseases that are often caused by a complex interplay between host factors, environmental influences and the intestinal microbiota. Not only improvements in endoscopic techniques, but also advances in high throughput sequencing technologies, have expanded knowledge of how intestinal diseases develop. This review discusses how the host interacts with intestinal microbiota by the direct contact of host receptors with highly conserved structural motifs or molecules of microbes and also by microbe-derived metabolites (produced by the microbe during adaptation to the gut environment), such as short-chain fatty acids, vitamins, bile acids and amino acids. These metabolites are recognised by metabolite-sensing receptors expressed by immune cells to influence functions of macrophages, dendritic cells and T cells, such as migration, conversion and maintenance of regulatory T cells and regulation of proinflammatory cytokine production, which is essential for the maintenance of intestinal homeostasis and the development of intestinal diseases, such as inflammatory bowel diseases. First interventions in these complex interactions between microbe-derived metabolites and the host immune system for the treatment of gastrointestinal diseases, such as modification of the diet, treatment with antibiotics, application of probiotics and faecal microbiota transplantation, have been introduced into the clinic. Specific targeting of metabolite sensing receptors for the treatment of gastrointestinal diseases is in development. In future, precision medicine approaches that consider individual variability in genes, the microbiota, the environment and lifestyle will become increasingly important for the care of patients with gastrointestinal diseases.}, }
@article {pmid27043494, year = {2016}, author = {Peuker, K and Muff, S and Wang, J and Künzel, S and Bosse, E and Zeissig, Y and Luzzi, G and Basic, M and Strigli, A and Ulbricht, A and Kaser, A and Arlt, A and Chavakis, T and van den Brink, GR and Schafmayer, C and Egberts, JH and Becker, T and Bianchi, ME and Bleich, A and Röcken, C and Hampe, J and Schreiber, S and Baines, JF and Blumberg, RS and Zeissig, S}, title = {Epithelial calcineurin controls microbiota-dependent intestinal tumor development.}, journal = {Nature medicine}, volume = {22}, number = {5}, pages = {506-515}, pmid = {27043494}, issn = {1546-170X}, support = {R37 DK044319/DK/NIDDK NIH HHS/United States ; R01 DK088199/DK/NIDDK NIH HHS/United States ; R01 DK051362/DK/NIDDK NIH HHS/United States ; R01 DK053056/DK/NIDDK NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; R01 DK044319/DK/NIDDK NIH HHS/United States ; R56 DK053056/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Blotting, Western ; Calcineurin/*metabolism ; Cell Proliferation ; Cell Survival ; Colorectal Neoplasms/*metabolism/microbiology/mortality ; Disease Models, Animal ; Electrophoretic Mobility Shift Assay ; Epithelial Cells/*metabolism ; Fecal Microbiota Transplantation ; Flow Cytometry ; Gastrointestinal Microbiome/genetics/*physiology ; Genes, APC ; HCT116 Cells ; HT29 Cells ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Intestinal Mucosa/*metabolism ; Intestinal Neoplasms/*metabolism/microbiology ; Intestines/microbiology ; Mice ; NFATC Transcription Factors/*metabolism ; Neoplastic Stem Cells ; Organoids ; Prognosis ; RNA, Ribosomal, 16S/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Array Analysis ; }, abstract = {Inflammation-associated pathways are active in intestinal epithelial cells (IECs) and contribute to the pathogenesis of colorectal cancer (CRC). Calcineurin, a phosphatase required for the activation of the nuclear factor of activated T cells (NFAT) family of transcription factors, shows increased expression in CRC. We therefore investigated the role of calcineurin in intestinal tumor development. We demonstrate that calcineurin and NFAT factors are constitutively expressed by primary IECs and selectively activated in intestinal tumors as a result of impaired stratification of the tumor-associated microbiota and toll-like receptor signaling. Epithelial calcineurin supports the survival and proliferation of cancer stem cells in an NFAT-dependent manner and promotes the development of intestinal tumors in mice. Moreover, somatic mutations that have been identified in human CRC are associated with constitutive activation of calcineurin, whereas nuclear translocation of NFAT is associated with increased death from CRC. These findings highlight an epithelial cell-intrinsic pathway that integrates signals derived from the commensal microbiota to promote intestinal tumor development.}, }
@article {pmid27043242, year = {2016}, author = {Merlo, G and Graves, N and Brain, D and Connelly, LB}, title = {Economic evaluation of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection in Australia.}, journal = {Journal of gastroenterology and hepatology}, volume = {31}, number = {12}, pages = {1927-1932}, doi = {10.1111/jgh.13402}, pmid = {27043242}, issn = {1440-1746}, mesh = {Anti-Bacterial Agents/economics/therapeutic use ; Australia ; Clostridioides difficile/*pathogenicity ; Cost Savings ; Cost-Benefit Analysis ; Drug Costs ; Enterocolitis, Pseudomembranous/diagnosis/*economics/microbiology/*surgery ; Fecal Microbiota Transplantation/adverse effects/*economics ; *Gastrointestinal Microbiome ; *Health Care Costs ; Humans ; Intestines/*microbiology ; Markov Chains ; Models, Economic ; Quality of Life ; Quality-Adjusted Life Years ; Recurrence ; Time Factors ; Treatment Outcome ; Vancomycin/economics/therapeutic use ; }, abstract = {BACKGROUND AND AIM: Clostridium difficile is the most common cause of hospital-acquired diarrhea in Australia. In 2013, a randomized controlled trial demonstrated the effectiveness of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). The aim of this study is to evaluate the cost-effectiveness of fecal microbiota transplantation-via either nasoduodenal or colorectal delivery-compared with vancomycin for the treatment of recurrent CDI in Australia.<br><br>METHODS: A Markov model was developed to compare the cost-effectiveness of fecal microbiota transplantation compared with standard antibiotic therapy. A literature review of clinical evidence informed the structure of the model and the choice of parameter values. Clinical effectiveness was measured in terms of quality-adjusted life years. Uncertainty in the model was explored using probabilistic sensitivity analysis.<br><br>RESULTS: Both nasoduodenal and colorectal FMT resulted in improved quality of life and reduced cost compared with vancomycin. The incremental effectiveness of either FMT delivery compared with vancomycin was 1.2 (95% CI: 0.1, 2.3) quality-adjusted life years, or 1.4 (95% CI: 0.4, 2.4) life years saved. Treatment with vancomycin resulted in an increased cost of AU$4094 (95% CI: AU$26, AU$8161) compared with nasoduodenal delivery of FMT and AU$4045 (95% CI: -AU$33, AU$8124) compared with colorectal delivery. The mean difference in cost between colorectal and nasoduodenal FMT was not significant.<br><br>CONCLUSIONS: If FMT, rather than vancomycin, became standard care for recurrent CDI in Australia, the estimated national healthcare savings would be over AU$4000 per treated person, with a substantial increase in quality of life.}, }
@article {pmid27028536, year = {2016}, author = {Kyburz, A and Müller, A}, title = {The Gastrointestinal Tract Microbiota and Allergic Diseases.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {34}, number = {3}, pages = {230-243}, doi = {10.1159/000443357}, pmid = {27028536}, issn = {1421-9875}, mesh = {Animals ; Clinical Trials as Topic ; *Gastrointestinal Microbiome/drug effects ; Humans ; Hypersensitivity/immunology/*microbiology ; Immune Tolerance/drug effects ; Immunologic Factors/pharmacology/therapeutic use ; Risk Factors ; }, abstract = {The gastrointestinal (GI) tract microbiota is required for optimal digestion of foods, for the development of resistance against pathogens (termed colonization resistance), for the development of mucosa-associated lymphoid tissue, and for local as well as systemic immune homeostasis. Certain constituents of the GI tract microbiota are widely recognized as critical regulators and modulators of their host's immune response. These include bacterial members of the microbiota as well as parasitic nematodes. Immune regulation by immunomodulatory members of the GI microbiota primarily serves to subvert host antimicrobial immune defenses and promote persistent colonization, but as a side effect may prevent or suppress immunological disorders resulting from inappropriate responses to harmless antigens, such as allergy, colitis or autoimmunity. Many of the best understood GI-resident immunomodulatory species have co-evolved with their mammalian hosts for tens of thousands of years and masterfully manipulate host immune responses. In this review, we discuss the epidemiological evidence for the role of the GI tract microbiota as a whole, and of specific members, in protection against allergic and other immunological disorders. We then focus on the mechanistic basis of microbial immunomodulation, which is presented using several well-understood paradigmatic examples, that is, helminths, Helicobacter pylori, Bifidobacteria and Lactobacilli. In a final chapter, we highlight past and ongoing attempts at harnessing the immunomodulatory properties of GI microbiota species and their secreted products for intervention studies and describe the promises and limitations of these experimental approaches. The effects of pro- and prebiotics, bacterial lysates, as well as of fecal microbiota transplantation are presented and compared.}, }
@article {pmid27027524, year = {2016}, author = {Cammarota, G and Pecere, S and Ianiro, G and Masucci, L and Currò, D}, title = {Principles of DNA-Based Gut Microbiota Assessment and Therapeutic Efficacy of Fecal Microbiota Transplantation in Gastrointestinal Diseases.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {34}, number = {3}, pages = {279-285}, doi = {10.1159/000443362}, pmid = {27027524}, issn = {1421-9875}, mesh = {DNA/*metabolism ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Diseases/*therapy ; *Gastrointestinal Microbiome ; Humans ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT), a process by which the normal gastrointestinal microbiota is restored, has demonstrated extraordinary cure rates for Clostridium difficile infection and low recurrence. The community of microorganisms within the human gut (or microbiota) is critical to health status and functions; therefore, together with the rise of FMT, the gastrointestinal microbiota has emerged as a 'virtual' organ with a level of complexity comparable to that of any other organ system and capable to compete with powerful known antibiotics for the treatment of several disorders. Although treatment protocols, donor selection, stool preparation and delivery methods varied widely, with a few reports following an identical protocol, FMT has diffused to other areas where the alterations of the gut microbiota ecology (or dysbiosis) have been theorized to play a causative role, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), among several other extra-intestinal disorders (i.e. metabolic syndrome and obesity, multiple sclerosis, cardiovascular diseases). FMT can be relatively simple to perform, but a number of challenges need to be overcome before this procedure is widely accepted in clinical practice, and currently, there is no consensus between the various gastrointestinal organizations and societies regarding the FMT procedure. In this article, we describe the modern high-throughput sequencing techniques to characterize the composition of gut microbiota and the potential for therapeutics by manipulating microbiota with FMT in several gastrointestinal disorders (C. difficile-associated diarrhea, IBD and IBS), with a look on the potential future directions of FMT.}, }
@article {pmid27025836, year = {2016}, author = {Millan, B and Park, H and Hotte, N and Mathieu, O and Burguiere, P and Tompkins, TA and Kao, D and Madsen, KL}, title = {Fecal Microbial Transplants Reduce Antibiotic-resistant Genes in Patients With Recurrent Clostridium difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {62}, number = {12}, pages = {1479-1486}, pmid = {27025836}, issn = {1537-6591}, support = {93675//CIHR/Canada ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/pharmacology ; Clostridioides difficile/*drug effects/genetics ; Drug Resistance, Bacterial/*genetics ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Male ; Middle Aged ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (RCDI) is associated with repeated antibiotic treatment and the enhanced growth of antibiotic-resistant microbes. This study tested the hypothesis that patients with RCDI would harbor large numbers of antibiotic-resistant microbes and that fecal microbiota transplantation (FMT) would reduce the number of antibiotic-resistant genes.<br><br>METHODS: In a single center study, patients with RCDI (n = 20) received FMT from universal donors via colonoscopy. Stool samples were collected from donors (n = 3) and patients prior to and following FMT. DNA was extracted and shotgun metagenomics performed. Results as well as assembled libraries from a healthy cohort (n = 87) obtained from the Human Microbiome Project were aligned against the NCBI bacterial taxonomy database and the Comprehensive Antibiotic Resistance Database. Results were corroborated through a DNA microarray containing 354 antibiotic resistance (ABR) genes.<br><br>RESULTS: RCDI patients had a greater number and diversity of ABR genes compared with donors and healthy controls. Beta-lactam, multidrug efflux pumps, fluoroquinolone, and antibiotic inactivation ABR genes were increased in RCDI patients, although donors primarily had tetracycline resistance. RCDI patients were dominated by Proteobacteria with Escherichia coli and Klebsiella most prevalent. FMT resulted in a resolution of symptoms that correlated directly with a decreased number and diversity of ABR genes and increased Bacteroidetes and Firmicutes with reduced Proteobacteria. ABR gene profiles were maintained in recipients for up to a year following FMT.<br><br>CONCLUSIONS: RCDI patients have increased numbers of antibiotic-resistant organisms. FMT is effective in the eradication of pathogenic antibiotic-resistant organisms and elimination of ABR genes.}, }
@article {pmid27025827, year = {2016}, author = {Halpin, AL and McDonald, LC}, title = {Editorial Commentary: The Dawning of Microbiome Remediation for Addressing Antibiotic Resistance.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {62}, number = {12}, pages = {1487-1488}, pmid = {27025827}, issn = {1537-6591}, support = {CC999999//Intramural CDC HHS/United States ; }, mesh = {*Drug Resistance, Microbial ; Humans ; *Microbiota ; }, }
@article {pmid27025573, year = {2016}, author = {Du, J and Lan, Z and Liu, Y and Liu, Y and Yu, Q and Li, Y and Guo, T}, title = {Evaluation of oral Lanzhou lamb rotavirus vaccine via passive transfusion with CD4(+)/CD8(+) T lymphocytes.}, journal = {Virus research}, volume = {217}, number = {}, pages = {101-106}, doi = {10.1016/j.virusres.2016.03.006}, pmid = {27025573}, issn = {1872-7492}, mesh = {*Adoptive Transfer ; Animals ; CD4-Positive T-Lymphocytes/*immunology/transplantation ; CD8-Positive T-Lymphocytes/*immunology/transplantation ; Cell Separation ; Female ; Immunoglobulin A/blood ; Immunoglobulin A, Secretory/blood ; Immunoglobulin G/blood ; Mice ; Mice, Inbred BALB C ; Rotavirus Infections ; Rotavirus Vaccines/*immunology ; Virus Shedding ; }, abstract = {Lanzhou Lamb derived Rotavirus (RV) Vaccine (namely LLR) for children is only used in China. Since there were no reports on evaluation of LLR, even the data of phase IV clinical trial, we proceed the evaluation of LLR through focusing on T-cell to investigate whether LLR could induce the potential function involving in protection as a vaccine. Four groups of nude mice were transfused with CD4(+)/CD8(+) T-cells isolated from LLR-immunized (primed) and LLR-unimmunized (naïve) mice via intraperitonea (i.p.) respectively. Consequently, the adoption mice were challenged with mice-origin wild rotavirus EDIM (Epizootic Diarrhea of Infant Mice) by intragastric administration. Series of fecal/serum samples were collected and viral shedding, then serum IgA/IgG and secreted IgA were assayed. Compared to the mice transfused with T lymphocytes from naïve mice, the nude mice transfused with CD4(+) T lymphocytes from primed mice induce fecal and serum IgA increasing more rapidly, and have a shorter duration of virus shedding too. Whereas, no significant difference in virus clearance was found between the mice transfused with CD8(+) T lymphocytes isolated from primed and naïve mice. Therefore, we cleared the distinct roles of transfused CD4(+)/CD8(+) T lymphocytes for rotavirus clearance in nude mice, that the viral clearance conducted by CD4(+) T lymphocytes. Meanwhile, it has ability to help induction of LLR specific immunogenicity. Comparing with the transfusion of cell from primed and naïve mice, LLR can induce CD4(+) T lymphocytes memory which is a potential index to reflect the immunogenicity and protection, while CD8(+) T lymphocytes remove rotavirus by CTL with little memory ability.}, }
@article {pmid27025251, year = {2016}, author = {Chehoud, C and Dryga, A and Hwang, Y and Nagy-Szakal, D and Hollister, EB and Luna, RA and Versalovic, J and Kellermayer, R and Bushman, FD}, title = {Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation.}, journal = {mBio}, volume = {7}, number = {2}, pages = {e00322}, pmid = {27025251}, issn = {2150-7511}, support = {U01 CA170930/CA/NCI NIH HHS/United States ; T32 AI007632/AI/NIAID NIH HHS/United States ; R01 AI082020/AI/NIAID NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; AI082020/AI/NIAID NIH HHS/United States ; P30DK56338/DK/NIDDK NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; }, mesh = {*Biodiversity ; Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation/*adverse effects ; Humans ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Viruses/*classification/genetics/*isolation &amp; purification ; }, abstract = {UNLABELLED: Fecal microbiota transplantation (FMT) is a highly effective treatment for refractoryClostridium difficileinfections. However, concerns persist about unwanted cotransfer of pathogenic microbes such as viruses. Here we studed FMT from a single healthy human donor to three pediatric ulcerative colitis patients, each of whom received a course of 22 to 30 FMT treatments. Viral particles were purified from donor and recipient stool samples and sequenced; the reads were then assembled into contigs corresponding to viral genomes or partial genomes. Transfer of selected viruses was confirmed by quantitative PCR. Viral contigs present in the donor could be readily detected in recipients, with up to 32 different donor viral contigs appearing in a recipient sample. Reassuringly, none of these were viruses are known to replicate on human cells. Instead, viral contigs either scored as bacteriophage or could not be attributed taxonomically, suggestive of unstudied phage. The two most frequently transferred gene types were associated with temperate-phage replication. In addition, members ofSiphoviridae, the group of typically temperate phages that includes phage lambda, were found to be transferred with significantly greater efficiency than other groups. On the basis of these findings, we propose that the temperate-phage replication style may promote efficient phage transfer between human individuals. In summary, we documented transfer of multiple viral lineages between human individuals through FMT, but in this case series, none were from viral groups known to infect human cells.<br><br>IMPORTANCE: Transfer of whole communities of viruses between humans has rarely been studied but is of likely medical importance. Here we studied fecal microbiota transplantation (FMT), a highly successful treatment for relapsingClostridium difficileinfection and, potentially, other gastrointestinal (GI) diseases. We investigated the transfer of viral communities during FMT and documented transfer of multiple viral lineages between humans. None of these were viruses that replicated on animal cells or that are known to be pathogenic. We found that temperate bacteriophage, which form stable associations with their hosts, were significantly more likely to be transferred during FMT. This supports a model in which the viral temperate replication style may have evolved in part to support efficient viral transmission between environments.}, }
@article {pmid27019327, year = {2016}, author = {Benakis, C and Brea, D and Caballero, S and Faraco, G and Moore, J and Murphy, M and Sita, G and Racchumi, G and Ling, L and Pamer, EG and Iadecola, C and Anrather, J}, title = {Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells.}, journal = {Nature medicine}, volume = {22}, number = {5}, pages = {516-523}, pmid = {27019327}, issn = {1546-170X}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 NS081179/NS/NINDS NIH HHS/United States ; R01 NS034179/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Behavior, Animal ; Blood-Brain Barrier/metabolism ; Brain/*immunology/metabolism/physiopathology ; Brain Ischemia/immunology/microbiology/physiopathology ; Dendritic Cells/*immunology ; Dysbiosis/*immunology/microbiology ; Fecal Microbiota Transplantation ; Flow Cytometry ; Gastrointestinal Microbiome/drug effects/genetics/*immunology ; Immunity, Mucosal/immunology ; Immunohistochemistry ; Infarction, Middle Cerebral Artery/*immunology/microbiology/physiopathology ; Interleukin-10/immunology ; Interleukin-17/immunology ; Intestinal Mucosa/immunology ; Intestine, Small/immunology/microbiology ; Intestines/*immunology/microbiology ; Leukocytes/immunology ; Lymphocytes/immunology ; Mice ; RNA, Messenger/metabolism ; RNA, Ribosomal, 16S/genetics ; Receptors, Antigen, T-Cell, gamma-delta/*immunology ; Stroke/immunology/microbiology/physiopathology ; T-Lymphocytes/*immunology ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Commensal gut bacteria impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the microbiota has an impact on the outcome of acute brain injury. Here we show that antibiotic-induced alterations in the intestinal flora reduce ischemic brain injury in mice, an effect transmissible by fecal transplants. Intestinal dysbiosis alters immune homeostasis in the small intestine, leading to an increase in regulatory T cells and a reduction in interleukin (IL)-17-positive γδ T cells through altered dendritic cell activity. Dysbiosis suppresses trafficking of effector T cells from the gut to the leptomeninges after stroke. Additionally, IL-10 and IL-17 are required for the neuroprotection afforded by intestinal dysbiosis. The findings reveal a previously unrecognized gut-brain axis and an impact of the intestinal flora and meningeal IL-17(+) γδ T cells on ischemic injury.}, }
@article {pmid27018122, year = {2016}, author = {Stallmach, A and Lange, K and Buening, J and Sina, C and Vital, M and Pieper, DH}, title = {Fecal Microbiota Transfer in Patients With Chronic Antibiotic-Refractory Pouchitis.}, journal = {The American journal of gastroenterology}, volume = {111}, number = {3}, pages = {441-443}, pmid = {27018122}, issn = {1572-0241}, mesh = {Adult ; Drug Resistance, Bacterial ; Endoscopy, Gastrointestinal/methods ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; *Pouchitis/diagnosis/microbiology/therapy ; Treatment Outcome ; }, }
@article {pmid27017007, year = {2016}, author = {Woloszynek, S and Pastor, S and Mell, JC and Nandi, N and Sokhansanj, B and Rosen, GL}, title = {Engineering Human Microbiota: Influencing Cellular and Community Dynamics for Therapeutic Applications.}, journal = {International review of cell and molecular biology}, volume = {324}, number = {}, pages = {67-124}, doi = {10.1016/bs.ircmb.2016.01.003}, pmid = {27017007}, issn = {1937-6448}, mesh = {Animals ; Bioethics ; *Genetic Engineering ; Humans ; *Microbiota ; Models, Biological ; Social Control, Formal ; }, abstract = {The complex relationship between microbiota, human physiology, and environmental perturbations has become a major research focus, particularly with the arrival of culture-free and high-throughput approaches for studying the microbiome. Early enthusiasm has come from results that are largely correlative, but the correlative phase of microbiome research has assisted in defining the key questions of how these microbiota interact with their host. An emerging repertoire for engineering the microbiome places current research on a more experimentally grounded footing. We present a detailed look at the interplay between microbiota and host and how these interactions can be exploited. A particular emphasis is placed on unstable microbial communities, or dysbiosis, and strategies to reestablish stability in these microbial ecosystems. These include manipulation of intermicrobial communication, development of designer probiotics, fecal microbiota transplantation, and synthetic biology.}, }
@article {pmid27015203, year = {2016}, author = {Lee, M and Chen, SC and Yang, HY and Huang, JH and Yeung, CY and Lee, HC}, title = {Infant Stool Color Card Screening Helps Reduce the Hospitalization Rate and Mortality of Biliary Atresia: A 14-Year Nationwide Cohort Study in Taiwan.}, journal = {Medicine}, volume = {95}, number = {12}, pages = {e3166}, pmid = {27015203}, issn = {1536-5964}, mesh = {Biliary Atresia/*diagnosis/*mortality/surgery ; Child, Preschool ; *Color ; Early Diagnosis ; Early Medical Intervention ; *Feces ; Female ; *Hospitalization ; Humans ; Infant ; Infant, Newborn ; Male ; *Mass Screening ; Predictive Value of Tests ; Survival Analysis ; Taiwan ; }, abstract = {Biliary atresia (BA) is a significant liver disease in children. Since 2004, Taiwan has implemented a national screening program that uses an infant stool color card (SCC) for the early detection of BA. The purpose of this study was to examine the outcomes of BA cases before and after the launch of this screening program. The objectives of this study were to evaluate the rates of hospitalization, liver transplantation (LT), and mortality of BA cases before and after the program, and to examine the association between the hospitalization rate and survival outcomes.This was a population-based cohort study. BA cases born during 1997 to 2010 were identified from the Taiwan National Health Insurance Research Database. Sex, birth date, hospitalization date, LT, and death data were collected and analyzed. The hospitalization rate by 2 years of age (Hosp/2yr) was calculated to evaluate its association with the outcomes of LT or death.Among 513 total BA cases, 457 (89%) underwent the Kasai procedure. Of these, the Hosp/2yr was significantly reduced from 6.0 to 6.9/case in the earlier cohort (1997-2004) to 4.9 to 5.3/case in the later cohort (2005-2010). This hospitalization rate reduction was followed by a reduction in mortality from 26.2% to 15.9% after 2006. The Cox proportional hazards model showed a significant increase in the risk for both LT (hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 1.10-1.18) and death (HR = 1.05, 95% CI = 1.01-1.08) for each additional hospitalization. A multivariate logistic regression model found that cases with a Hosp/2yr >6 times had a significantly higher risk for both LT (adjusted odds ratio [aOR] = 4.35, 95% CI = 2.82-6.73) and death (aOR = 1.75, 95% CI = 1.17-2.62).The hospitalization and mortality rates of BA cases in Taiwan were significantly and coincidentally reduced after the launch of the SCC screening program. There was a significant association between the hospitalization rate and final outcomes of LT or death. The SCC screening program can help reduce the hospitalization rate and mortality of BA cases and bring great financial benefit.}, }
@article {pmid27012594, year = {2016}, author = {Buttó, LF and Haller, D}, title = {Dysbiosis in intestinal inflammation: Cause or consequence.}, journal = {International journal of medical microbiology : IJMM}, volume = {306}, number = {5}, pages = {302-309}, doi = {10.1016/j.ijmm.2016.02.010}, pmid = {27012594}, issn = {1618-0607}, mesh = {Animals ; Disease Models, Animal ; *Dysbiosis ; Ecosystem ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology/*pathology ; }, abstract = {The intestinal microbiota encompasses hundreds of bacterial species that constitute a relatively stable ecosystem. Alteration in the microbiota composition may arise from infections, immune defects, metabolic alterations, diet or antibiotic treatment. Dysbiosis is considered as an alteration in microbiota community structure and/or function, capable of causing/driving a detrimental distortion of microbe-host homeostasis. A variety of pathologies are associated with changes in the community structure and function of the gut microbiota, suggesting a link between dysbiosis and disease etiology. With an emphasis in this review on inflammatory bowel diseases (IBD), the non-trivial question is whether dysbiosis is the cause or consequence of inflammation. It is important to understand whether changes in microbial ecosystems are causally linked to the pathology and to what extend disease risk is predicable based on characteristic changes in community structure and/or function. Local changes in tissue integrity associated with focal areas of inflammation may result in the selection of a dysbiotic bacterial community associated with the propagation of a disease phenotype. This review outlines the role of dysbiosis in intestinal inflammation with particular focus on IBD-relevant gnotobiotic mouse models, the factors implicated in the development of dysbiosis and the means available to investigate dysbiosis in the context of human diseases.}, }
@article {pmid27011526, year = {2015}, author = {Lalwani, S and Varma, V and Kumaran, V and Mehta, N and Nundy, S}, title = {Complex Rectovaginal Fistula-an Experience at a Tertiary Care Centre.}, journal = {The Indian journal of surgery}, volume = {77}, number = {Suppl 3}, pages = {1142-1147}, pmid = {27011526}, issn = {0972-2068}, abstract = {Complex rectovaginal fistulae are difficult to manage. With an initial failed attempt, a simple fistula becomes complex and the success rate of a subsequent repair decreases. A review of our prospectively maintained records over a period of 16 years revealed 25 patients with rectovaginal fistulae. A variety of procedures was performed in these patients according to their aetiology, site and if there had been a previous attempt at repair. The mean age of the patients was 45 years. The most common cause was operative trauma in 14 cases. Ten patients had previous attempts at repair which had not been successful. The surgical procedures we performed included re-enforcement flaps, resection with diversion, repair with re-enforcement with omentum and simple diversion. Two patients developed recurrence, and one of them healed after a second repair. No recurrence developed in 10 patients who had failed attempts at repair elsewhere. Our experience has shown that most complex rectovaginal fistulae can be successfully repaired but they might require repeated operations. Faecal diversion is usually necessary, and in recurrent fistulae, we found that rather than a local repair, a muscle flap or omental interposition improves the chances of healing.}, }
@article {pmid27003147, year = {2016}, author = {Martins, FS}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis: FoMenTing Change?.}, journal = {Digestive diseases and sciences}, volume = {61}, number = {8}, pages = {2154-2155}, pmid = {27003147}, issn = {1573-2568}, mesh = {*Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Microbiota ; }, }
@article {pmid26995779, year = {2016}, author = {Adam, B and Koldehoff, M and Ditschkowski, M and Gromke, T and Hlinka, M and Trenschel, R and Kordeals, L and Steckel, NK and Beelen, DW and Liebregts, T}, title = {Endoscopic and Histological Findings Are Predicted by Fecal Calprotectin in Acute Intestinal Graft-Versus-Host-Disease.}, journal = {Digestive diseases and sciences}, volume = {61}, number = {7}, pages = {2019-2026}, pmid = {26995779}, issn = {1573-2568}, mesh = {Adult ; Aged ; Biomarkers ; Feces/*chemistry ; Female ; Gastrointestinal Diseases/etiology ; Graft vs Host Disease/*diagnosis/metabolism ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Leukocyte L1 Antigen Complex/*chemistry ; Male ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Gastrointestinal graft-versus-host-disease (GI-GVHD) is a major cause of nonrelapse mortality after hematopoietic stem cell transplantation (HSCT) necessitating endoscopic examinations and biopsies for diagnosis. Fecal calprotectin (CPT) has been widely used in gastrointestinal inflammation, but comprehensive data in GI-GVHD are lacking.<br><br>AIMS: We aimed to identify an association of CPT with endoscopic findings, mucosal damage and symptoms for diagnosing and monitoring acute GI-GVHD.<br><br>METHODS: Symptoms were prospectively evaluated in 110 consecutive HSCT recipients by standardized questionnaires and Bristol Stool Scale (BSS). CPT was assayed by ELISA. Symptom assessment and CPT were performed weekly and with onset of first symptoms. GVHD was diagnosed according to the Glucksberg criteria and by endoscopic biopsies. Patients with GI-GVHD received standard high-dose corticosteroid therapy and follow-up CPT, and symptom evaluation was performed after 28&#xa0;days. Patients not responding to steroid treatment were re-evaluated by colonoscopy.<br><br>RESULTS: GI-GVHD was diagnosed in 40 patients. Twelve patients with GI symptoms and CMV colitis and 24 patients with isolated skin GVHD were included as control subjects. CPT was significantly higher in GI-GVHD compared to skin GVHD and CMV colitis. Endoscopic findings, histological grading, abdominal cramps, diarrhea, urgency and BSS correlated with CPT. At follow-up, CPT correlated with abdominal cramps, diarrhea, urgency and BSS. In steroid refractory patients, CPT level was still significantly associated with severity of mucosal damage.<br><br>CONCLUSION: CPT predicts endoscopic and histological findings in GI-GVHD and correlates with lower GI symptoms. It enables to discriminate GVHD from CMV colitis and to monitor therapeutic success.}, }
@article {pmid26986546, year = {2016}, author = {Ray, A and Jones, C}, title = {Does the donor matter? Donor vs patient effects in the outcome of a next-generation microbiota-based drug trial for recurrent Clostridium difficile infection.}, journal = {Future microbiology}, volume = {11}, number = {}, pages = {611-616}, doi = {10.2217/fmb.16.10}, pmid = {26986546}, issn = {1746-0921}, mesh = {Adult ; Clostridioides difficile/*physiology ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Patients ; Species Specificity ; Tissue Donors ; Treatment Outcome ; }, abstract = {AIM: To evaluate the impact of the donor material versus the patient in outcomes achieved with RBX2660, a microbiota-based drug under study for recurrent Clostridium difficile infection (CDI).<br><br>METHODS: RBX2660 was administered to patients enrolled in the previously reported Phase II PUNCH CD study under Rebiotix's Investigational New Drug submission to the US FDA. Four donors were used to prepare the RBX2660 drug product used in the study. The product was manufactured in individual, donor-specific batches that could be tracked to individual patients and their outcomes. Donor products were randomized to patients for both first and second doses.<br><br>RESULTS: The individual donor or donor dose order did not significantly affect the outcome of RBX2660 treatment in 34 patients (mean age 68.8 years).<br><br>CONCLUSION: The specific donor did not affect the outcomes achieved with administration of RBX2660 for recurrent CDI.}, }
@article {pmid26982451, year = {2016}, author = {Hourigan, SK and Oliva-Hemker, M}, title = {Fecal microbiota transplantation in children: a brief review.}, journal = {Pediatric research}, volume = {80}, number = {1}, pages = {2-6}, pmid = {26982451}, issn = {1530-0447}, mesh = {Adult ; Child ; Child, Preschool ; Clostridium Infections/*therapy ; Dysbiosis ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Humans ; Infant ; Inflammatory Bowel Diseases/*therapy ; Intestines ; Microbiota ; Pediatrics/methods ; Recurrence ; Risk Factors ; Treatment Outcome ; }, abstract = {There has been a growing interest in fecal microbiota transplantation (FMT) over recent years, in part due to the increasing prevalence of Clostridium difficile infection (CDI) and expanding association of intestinal dysbiosis with a wide range of human diseases. Many adult studies have shown that FMT is an effective treatment for recurrent CDI and may possibly have applications in other illnesses such as inflammatory bowel disease (IBD); however, there is a paucity of data available in children who may differ from adults for many reasons including having a dynamic developing microbiome compared to adults who have a relatively stable microbiome. Here, we review published studies looking at FMT in children, for CDI and IBD, and discuss special considerations needed when conducting FMT in children.}, }
@article {pmid26974758, year = {2017}, author = {Furuya-Kanamori, L and Doi, SA and Paterson, DL and Helms, SK and Yakob, L and McKenzie, SJ and Garborg, K and Emanuelsson, F and Stollman, N and Kronman, MP and Clark, J and Huber, CA and Riley, TV and Clements, AC}, title = {Upper Versus Lower Gastrointestinal Delivery for Transplantation of Fecal Microbiota in Recurrent or Refractory Clostridium difficile Infection: A Collaborative Analysis of Individual Patient Data From 14 Studies.}, journal = {Journal of clinical gastroenterology}, volume = {51}, number = {2}, pages = {145-150}, doi = {10.1097/MCG.0000000000000511}, pmid = {26974758}, issn = {1539-2031}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Infant ; Lower Gastrointestinal Tract/*microbiology ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Upper Gastrointestinal Tract/*microbiology ; Young Adult ; }, abstract = {GOALS: The aim of this study was to compare upper gastrointestinal (UGI) versus lower gastrointestinal (LGI) delivery routes of fecal microbiota transplantation (FMT) for refractory or recurrent/relapsing Clostridium difficile infection (CDI).<br><br>BACKGROUND: FMT has been proven to be a safe and highly effective therapeutic option for CDI. Delivery, however, could be via the UGI or LGI routes, and it is unclear as to which route provides better clinical outcome.<br><br>STUDY: A systematic search for studies that reported the use of FMT for CDI treatment was conducted. Individual patient data that included demographic (age and sex) and clinical (route of FMT delivery, CDI outcome after FMT, and follow-up time) information were obtained. Kaplan-Meier cumulative hazard curves and Cox proportional hazard models were used to assess clinical failure after FMT by the route of delivery.<br><br>RESULTS: Data from 305 patients treated with FMT (208 via LGI route and 97 via UGI route) for CDI were analyzed. At 30 and 90 days, the risk of clinical failure was 5.6% and 17.9% in the UGI group compared with 4.9% and 8.5% in the LGI delivery route group, respectively. A time-varying analysis suggested a 3-fold increase in hazard of clinical failure for UGI delivery (hazard ratio, 3.43; 95% confidence interval, 1.32-8.93) in the period after 30 days.<br><br>CONCLUSIONS: FMT delivered via the LGI seems to be the most effective route for the prevention of recurrence/relapse of CDI. A randomized controlled trial is necessary to confirm whether FMT delivered via the LGI is indeed superior to that delivered via the UGI route.}, }
@article {pmid26968595, year = {2016}, author = {Schulberg, J and De Cruz, P}, title = {Characterisation and therapeutic manipulation of the gut microbiome in inflammatory bowel disease.}, journal = {Internal medicine journal}, volume = {46}, number = {3}, pages = {266-273}, doi = {10.1111/imj.13003}, pmid = {26968595}, issn = {1445-5994}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Inflammatory Bowel Diseases/*diagnosis/drug therapy/*microbiology ; Probiotics/administration &amp; dosage ; }, abstract = {Inflammatory bowel diseases are thought to develop as a result of dysregulation of the relationship that exists between the gut microbiota, host genetics and the immune system. The advent of culture-independent techniques has revolutionised the ability to characterise the role of the gut microbiota in health and disease based on the microbiota's genetic make-up. Inflammatory bowel diseases are characterised by dysbiosis which is an imbalance between pro- and anti-inflammatory bacteria and a reduction in bacterial diversity. Emerging data suggest that it is not only the presence of the gut microbiota but the functional activity of the microbiota that appears to play an important role in health and disease. Current strategies to manipulate therapeutically the gut microbiota using dietary modification, prebiotics, probiotics, antibiotics and faecal microbiota transplantation aim to restore the balance to a state of normobiosis. However, the ability of such strategies to correct dysbiosis and thereby achieve therapeutic benefit is yet to be fully characterised.}, }
@article {pmid26965890, year = {2016}, author = {Hernández-Rocha, C and Pidal, P and Ajenjo, MC and Quera, R and Quintanilla, M and Lubascher, J and Jemenao, MI and Ibáñez, P and Álvarez-Lobos, M and Diomedi, A and Marcotti, A and Acuña, M and Arab, JP and Riquelme, A and Candía, R and Carvajal, S}, title = {[Chilean consensus of prevention, diagnosis and treatment of Clostridium difficile-associated diarrhea].}, journal = {Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia}, volume = {33}, number = {1}, pages = {98-118}, doi = {10.4067/S0716-10182016000100020}, pmid = {26965890}, issn = {0717-6341}, mesh = {Chile ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/drug therapy/prevention &amp; control ; Consensus ; Diarrhea/*microbiology ; Humans ; }, abstract = {BACKGROUND: Clostridium dijfficile-associated diarrhea (CDAD) has become very important due to the increase in its incidence, severity, recurrence and the associated economic burden. Having a national consensus guideline is essential to improve its management.<br><br>OBJECTIVE: To build a multidisciplinary and evidence-based consensus in prevention, diagnosis and treatment of CDAD.<br><br>METHODS: We convened a panel of experts in the field of infectious diseases, gastroenterology, evidence-based medicine and consensus methodology. The panel conducted a structured review of published literature in CDAD evaluating evidence levels and recommendation degree according to the methodology proposed by the GRADE working-group. A modified three-round Delphi technique was used to reach a consensus among the experts.<br><br>RESULTS: A group of 16 experts was established, 12 of them answered 18 clinically relevant questions. The levels of agreement achieved by the panel of 16 experts were 79% in the first round and 100% in the second and third round. The main consensus recommendations in prevention are: restricting the use of proton-pump inhibitors, primary prophylaxis with probiotics in antibiotics users, education of health personnel, isolation for patients hospitalized with CDAD, and cleaning the rooms exposed to C. difficile with products based in chlorine or hydrogen peroxide. In the diagnosis: use of biology molecular-based techniques is preferred and if not available, glutamate dehydrogenase-based algorithms may be recommended. With regard to treatment: the use of oral metronidazole in mild-moderate CDAD and oral vancomycin in severe CDAD are recommended. Treat the first recurrence with the same antibiotics according to severity. In the case of second and subsequent recurrences consider prolonged therapy with vancomycin, rifaximin or fecal microbiota transplant.<br><br>CONCLUSION: The first Chilean consensus on prevention, diagnosis and treatment of CDAD is presented, which is a major step in improving national standards in the management of this disease.}, }
@article {pmid26960790, year = {2016}, author = {Biliński, J and Grzesiowski, P and Muszyński, J and Wróblewska, M and Mądry, K and Robak, K and Dzieciątkowski, T and Wiktor-Jedrzejczak, W and Basak, GW}, title = {Fecal Microbiota Transplantation Inhibits Multidrug-Resistant Gut Pathogens: Preliminary Report Performed in an Immunocompromised Host.}, journal = {Archivum immunologiae et therapiae experimentalis}, volume = {64}, number = {3}, pages = {255-258}, pmid = {26960790}, issn = {1661-4917}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Antineoplastic Agents/adverse effects ; Drug Resistance, Bacterial ; Drug Resistance, Multiple ; Dysbiosis/therapy ; Escherichia coli ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; *Immunocompromised Host ; Intestinal Mucosa/*microbiology ; Klebsiella pneumoniae ; Male ; Microbiota ; Middle Aged ; Multiple Myeloma/complications/drug therapy ; Phenotype ; Young Adult ; }, abstract = {Colonization of the gastrointestinal tract with multidrug-resistant (MDR) bacteria is a consequence of gut dysbiosis. We describe the successful utilization of fecal microbiota transplantation to inhibit Klebsiella pneumoniae MBL(+) and Escherichia coli ESBL(+) gut colonization in the immunocompromised host as a novel tool in the battle against MDR microorganisms. ClinicalTrials.gov identifier NCT02461199.}, }
@article {pmid26956193, year = {2016}, author = {Choi, HH and Cho, YS}, title = {Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives.}, journal = {Clinical endoscopy}, volume = {49}, number = {3}, pages = {257-265}, pmid = {26956193}, issn = {2234-2400}, abstract = {Fecal microbiota transplantation (FMT) is the infusion of liquid filtrate feces from a healthy donor into the gut of a recipient to cure a specific disease. A fecal suspension can be administered by nasogastric or nasoduodenal tube, colonoscope, enema, or capsule. The high success rate and safety in the short term reported for recurrent Clostridium difficile infection has elevated FMT as an emerging treatment for a wide range of disorders, including Parkinson's disease, fibromyalgia, chronic fatigue syndrome, myoclonus dystopia, multiple sclerosis, obesity, insulin resistance, metabolic syndrome, and autism. There are many unanswered questions regarding FMT, including donor selection and screening, standardized protocols, long-term safety, and regulatory issues. This article reviews the efficacy and safety of FMT used in treating a variety of diseases, methodology, criteria for donor selection and screening, and various concerns regarding FMT.}, }
@article {pmid26944009, year = {2016}, author = {Pakyz, AL and Moczygemba, LR and VanderWielen, LM and Edmond, MB}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection: The patient experience.}, journal = {American journal of infection control}, volume = {44}, number = {5}, pages = {554-559}, doi = {10.1016/j.ajic.2016.01.018}, pmid = {26944009}, issn = {1527-3296}, support = {K08 HS018578/HS/AHRQ HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*prevention &amp; control ; *Fecal Microbiota Transplantation ; Female ; Humans ; Interviews as Topic ; Male ; Middle Aged ; *Patient Satisfaction ; Quality of Life ; *Secondary Prevention ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Although effectiveness of fecal microbiota transplantation (FMT) has been adequately documented, the patient experience of undergoing FMT has not.<br><br>METHODS: We carried out a qualitative interview study using semistructured questions relating to aspects of health pre-FMT, during FMT, and post-FMT periods with 17 participants. Inductive coding was used to identify core themes during the periods.<br><br>RESULTS: Pre-FMT themes included physical (continuous diarrhea and weight loss), mental (depression, wanting to die, and fear), quality of life (unable to perform normal activities), social support, and financial (medication costs) factors. Provider resistance/limited awareness were barriers to FMT. Participants reached a tipping point, experiencing feelings of hopelessness, which led them to pursue FMT. During FMT, participants commented on lack of a so-called ick factor. During the posttreatment period, participants experienced symptom relief, but had residual fears. Patient activation was present during all phases, including information seeking and empowerment.<br><br>CONCLUSIONS: During the pre-FMT period, participants experienced extreme discomfort and encountered FMT barriers. Undergoing FMT was reported as easy but residual fear remained. There were displays of patient activation at all FMT time periods, including the seeking of FMT. Participants could have benefited from having undergone FMT sooner, demonstrating a need for improvement in provider education and health system barriers regarding FMT.}, }
@article {pmid26939622, year = {2016}, author = {Cui, B and Li, P and Xu, L and Peng, Z and Xiang, J and He, Z and Zhang, T and Ji, G and Nie, Y and Wu, K and Fan, D and Zhang, F}, title = {Step-up fecal microbiota transplantation (FMT) strategy.}, journal = {Gut microbes}, volume = {7}, number = {4}, pages = {323-328}, pmid = {26939622}, issn = {1949-0984}, mesh = {Bacteria/genetics/growth &amp; development/*isolation &amp; purification ; Fecal Microbiota Transplantation/*methods/standards ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; }, abstract = {Gut dysbiosis is a characteristic of inflammatory bowel disease (IBD) and is believed to play a role in the pathogenesis of IBD. Fecal microbiota transplantation (FMT) is an effective strategy to restore intestinal microbial diversity and has been reported to have a potential therapeutic value in IBD. Our recent study reported a holistic integrative therapy called "step-up FMT strategy," which was beneficial in treating steroid-dependent IBD patients. This strategy consists of scheduled FMTs combined with steroids, anti-TNF-α antibody treatment or enteral nutrition. Herein, we will elaborate the strategy thoroughly, introducing the concept, potential indication, methodology, and safety of "step-up FMT strategy" in detail.}, }
@article {pmid26937040, year = {2016}, author = {Hensley-McBain, T and Zevin, AS and Manuzak, J and Smith, E and Gile, J and Miller, C and Agricola, B and Katze, M and Reeves, RK and Kraft, CS and Langevin, S and Klatt, NR}, title = {Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques.}, journal = {Journal of virology}, volume = {90}, number = {10}, pages = {4981-4989}, pmid = {26937040}, issn = {1098-5514}, support = {K22 AI098440/AI/NIAID NIH HHS/United States ; P51 OD010425/OD/NIH HHS/United States ; P51 OD011107/OD/NIH HHS/United States ; R01 AI120712/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; CD4-Positive T-Lymphocytes/drug effects/immunology ; Colon/microbiology/pathology ; Disease Models, Animal ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome/drug effects/immunology ; Genes, rRNA ; HIV Infections/immunology/microbiology/therapy/virology ; Humans ; Intestines/cytology/immunology/microbiology ; Lymphocyte Activation/drug effects ; Macaca mulatta ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; Simian Acquired Immunodeficiency Syndrome/*immunology/microbiology/*therapy ; Simian Immunodeficiency Virus/genetics/*immunology ; Th17 Cells/immunology ; Viral Load/drug effects ; }, abstract = {UNLABELLED: An altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT. The greatest microbiota shift was observed after antibiotic treatment. The bacterial community composition at 2 weeks post-FMT resembled the pre-FMT community structure, although differences in the abundances of minor bacterial populations remained. Immunologically, we observed significant increases in the number of peripheral Th17 and Th22 cells and reduced CD4(+) T cell activation in gastrointestinal tissues post-FMT. Importantly, the transplant was well tolerated with no negative clinical side effects. Although this pilot study did not control for the differential contributions of antibiotic treatment and FMT to the observed results, the data suggest that FMT may have beneficial effects that should be further evaluated in larger studies.<br><br>IMPORTANCE: Due to the immunodeficiency and chronic inflammation that occurs during HIV infection, determination of the safety of FMT is crucial to prevent deleterious consequences if it is to be used as a treatment in the future. Here we used the macaque model of HIV infection and performed FMT on six chronically SIV-infected rhesus macaques on antiretroviral treatment. In addition to providing a preclinical demonstration of the safety of FMT in primates infected with a lentivirus, this study provided a unique opportunity to examine the relationships between alterations to the microbiome and immunological parameters. In this study, we found increased numbers of Th17 and Th22 cells as well as decreased activation of CD4(+) T cells post-FMT, and these changes correlated most strongly across all sampling time points with lower-abundance taxonomic groups and other taxonomic groups in the colon. Overall, these data provide evidence that changes in the microbiome, particularly in terms of diversity and changes in minor populations, can enhance immunity and do not have adverse consequences.}, }
@article {pmid26934528, year = {2016}, author = {Meighani, A and Hart, BR and Mittal, C and Miller, N and John, A and Ramesh, M}, title = {Predictors of fecal transplant failure.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {28}, number = {7}, pages = {826-830}, doi = {10.1097/MEG.0000000000000614}, pmid = {26934528}, issn = {1473-5687}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Cross Infection/therapy ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Recurrence ; Retrospective Studies ; Risk Factors ; Sex Factors ; Survival Rate ; Treatment Failure ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is a significant healthcare burden, with increased morbidity and mortality. Traditional treatment regimens using antibiotics for recurrent CDI are significantly less successful compared with 80-90% with fecal microbiota transplantation (FMT). There is a paucity of data on failure rates and mortality after FMT in CDI. This study aims to identify the rates of failure, relapse, and mortality associated with FMT as well as the risk factors for FMT failure.<br><br>METHODS: A large retrospective cohort study was carried out including all patients who underwent FMT from December 2012 through May 2014. Patient factors (demographics, comorbidities, immune-suppression, transplant history, antibiotics used, hospitalization, and surgeries), disease factors (number of episodes of CDI, treatments, and severity), and transplant factors (route and number of FMT) were examined. Failure of treatment was defined as no resolution of diarrhea in patients who had been treated with one or more fecal microbiota transplantation within 90 days of FMT.<br><br>RESULTS: A total of 201 patients (age 66.6&#xb1;18.3 years, 62.2% women) were included. The overall failure rate was 12.4%. Patients with failed fecal transplant had increased number of FMTs compared with those who responded (mean 1.92&#xb1;0.997 vs. 1.29&#xb1;0.615; P=0.004). No colectomies or death related to CDI were found in our patient population. Significant predictors of failure were female sex (P=0.016), previous hospitalization (P=0.006), and surgery before FMT (P=0.005). The overall mortality rate was 9.0% and failure of FMT was associated with an increased risk of death (odds ratio=5.833, confidence interval 2.01-16.925; P<0.05).<br><br>CONCLUSION: FMT is a suitable alterative to antibiotic use for recurrent CDIs, with a high success rate. The results indicate that hospital-acquired CDI may be a predictor of failure of FMT.}, }
@article {pmid26934513, year = {2016}, author = {McFarland, LV}, title = {Therapies on the horizon for Clostridium difficile infections.}, journal = {Expert opinion on investigational drugs}, volume = {25}, number = {5}, pages = {541-555}, doi = {10.1517/13543784.2016.1161025}, pmid = {26934513}, issn = {1744-7658}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; Clostridium Infections/*drug therapy/prevention &amp; control ; Drugs, Investigational/therapeutic use ; Humans ; }, abstract = {INTRODUCTION: Clostridium difficile infections are a leading cause of healthcare facility outbreaks of gastrointestinal illness that may have serious complications and a high rate of recurrent disease. Despite the availability of standard antibiotic treatments, data from national surveillance programs indicate that the incidence of this disease continues to increase, placing a heavy burden on healthcare systems. New emerging strategies are being tested to replace or augment these standard antibiotics.<br><br>AREAS COVERED: Thirty-two current investigational agents focusing on different strategies for both prevention and treatment of C. difficile infections are reviewed. Data was gathered from a literature search of public databases for published trials from 1999-November 13, 2015 and from the author's compendium of knowledge. Agents reviewed included 13 antibiotics, two antibiotic inactivators, seven bacteria or yeasts acting to enhance the normal microbiome, seven immunizing agents and three toxin binders. Of the 32 investigational treatments reviewed, 8 (25%) showed significant efficacy in phase II or III clinical trials and are actively being developed as new therapies for C. difficile infections.<br><br>EXPERT OPINION: A number of potential treatments have floundered during their development process, while others have shown promising results. The strongest efficacy has been in the areas of newer antibiotics, probiotics, monoclonal antibodies and vaccines. By targeting the pathogenic pathway of C. difficile infections, multiple strategies for prevention and treatment have been developed.}, }
@article {pmid26929784, year = {2016}, author = {Gupta, S and Allen-Vercoe, E and Petrof, EO}, title = {Fecal microbiota transplantation: in perspective.}, journal = {Therapeutic advances in gastroenterology}, volume = {9}, number = {2}, pages = {229-239}, pmid = {26929784}, issn = {1756-283X}, support = {R21 AI121575/AI/NIAID NIH HHS/United States ; }, abstract = {There has been increasing interest in understanding the role of the human gut microbiome to elucidate the therapeutic potential of its manipulation. Fecal microbiota transplantation (FMT) is the administration of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition and confer a health benefit. FMT has been used to successfully treat recurrent Clostridium difficile infection. There are preliminary indications to suggest that it may also carry therapeutic potential for other conditions such as inflammatory bowel disease, obesity, metabolic syndrome, and functional gastrointestinal disorders.}, }
@article {pmid26927355, year = {2016}, author = {Kao, PC and Han, QJ and Liu, S and Li, XJ and Inman, KS and Chia, N}, title = {Letter to the Editor: The Surge of Type 2 Diabetes Mellitus in China - an International Alert: Physical Exercise and Low-Caloric Diet May Reduce the Risks of Type 2 Diabetes Mellitus and Dementia.}, journal = {Annals of clinical and laboratory science}, volume = {46}, number = {1}, pages = {114-118}, pmid = {26927355}, issn = {1550-8080}, mesh = {Bicycling ; China/epidemiology ; Diabetes Mellitus, Type 2/*epidemiology ; *Diet ; *Energy Intake ; *Exercise ; Feces/microbiology ; Female ; Humans ; *Internationality ; Male ; Mental Health ; Microbiota ; Prevalence ; Risk Factors ; }, abstract = {The prevalence of diabetes in China has surged from 0.67% before 1980 to 11.6% currently. It is even higher than the prevalence in the United States. Certainly, China's economic open-ups, improving living standard, and modernization have propagated the surge. From a traditional public-health point of view, increased food intake and decreased exercise were the main contributors. A new knowledge of colon microbiota could be applied to provide a second harvest of food energy; for example, large molecules of carbohydrates, which are undigested by the stomach and small intestine, produce by-products that the body can absorb in the colon. Colon microbiota can ferment these carbohydrates to the short-chain fatty acid butyrate. This is an energy source that may even cause nonalcoholic fatty liver. How these colon microbiota contribute to the surge of diabetes and whether this new knowledge can be used to control diabetes and metabolic syndrome are questions for future scientific studies. Clinically, however, colon microbiota have had immediate applications; fecal microbiota have been transplanted from healthy persons to treat recurrent Clostridium difficile infection at Mayo Clinic. In addition, a stool biobank of healthy persons was established at Mayo Clinic for future clinical applications.}, }
@article {pmid26925392, year = {2016}, author = {Jayasinghe, TN and Chiavaroli, V and Holland, DJ and Cutfield, WS and O'Sullivan, JM}, title = {The New Era of Treatment for Obesity and Metabolic Disorders: Evidence and Expectations for Gut Microbiome Transplantation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {6}, number = {}, pages = {15}, pmid = {26925392}, issn = {2235-2988}, mesh = {Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Metabolic Diseases/*therapy ; Obesity/*therapy ; Probiotics/*therapeutic use ; }, abstract = {Key Points: The microbiome has been implicated in the development of obesity. Conventional therapeutic methods have limited effectiveness for the treatment of obesity and prevention of related complications. Gut microbiome transplantation may represent an alternative and effective therapy for the treatment of obesity. Obesity has reached epidemic proportions. Despite a better understanding of the underlying pathophysiology and growing treatment options, a significant proportion of obese patients do not respond to treatment. Recently, microbes residing in the human gastrointestinal tract have been found to act as an "endocrine" organ, whose composition and functionality may contribute to the development of obesity. Therefore, fecal/gut microbiome transplantation (GMT), which involves the transfer of feces from a healthy donor to a recipient, is increasingly drawing attention as a potential treatment for obesity. Currently the evidence for GMT effectiveness in the treatment of obesity is preliminary. Here, we summarize benefits, procedures, and issues associated with GMT, with a special focus on obesity.}, }
@article {pmid26924753, year = {2016}, author = {Mattner, J and Schmidt, F and Siegmund, B}, title = {Faecal microbiota transplantation-A clinical view.}, journal = {International journal of medical microbiology : IJMM}, volume = {306}, number = {5}, pages = {310-315}, doi = {10.1016/j.ijmm.2016.02.003}, pmid = {26924753}, issn = {1618-0607}, mesh = {Clinical Trials as Topic ; Clostridioides difficile/isolation &amp; purification ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Inflammatory Bowel Diseases/*therapy ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation has gained increasing attention over the last decade as various phenotypes could be transferred from a donor to a recipient in different animal models. Clinically, however, the sole indication with evidence from a randomized placebo controlled trial is refractory Clostridium difficile infection. Despite revealing successful clinical outcomes, questions concerning regulatory affairs, the identification of the best donor, the optimal mixture of the transplant as well as the preferred route of administration remain to be clarified even for this indication. Initiated by the idea that alterations in the composition of the intestinal microbiota are associated with intestinal inflammation in inflammatory bowel disease, several studies investigated whether faecal microbiota transplantation would be an equally suitable approach for these devastating disorders. Indeed, the available data indicate changes in the microbiota composition following faecal microbial transplantation depending on the degree of intestinal inflammation. Furthermore, first data even provide evidence that the transplantation of an "optimized" microbiota induces clinical remission in ulcerative colitis. However, despite these intriguing results it needs to be considered that not only "a cure of inflammation", but also risk factors and phenotypes including obesity can be transferred via faecal microbiota transplantation. Thus, a deeper understanding of the impact of a distinct microbiota composition is required before "designing" the optimal faecal microbiota transplant.}, }
@article {pmid26922358, year = {2016}, author = {Iannone, A and Losurdo, G and Pricci, M and Girardi, B and Massaro, A and Principi, M and Barone, M and Ierardi, E and Di Leo, A}, title = {Stool Investigations for Colorectal Cancer Screening: From Occult Blood Test to DNA Analysis.}, journal = {Journal of gastrointestinal cancer}, volume = {47}, number = {2}, pages = {143-151}, pmid = {26922358}, issn = {1941-6636}, mesh = {Colorectal Neoplasms/*diagnosis ; DNA/*analysis ; Early Detection of Cancer/*methods ; Feces/*cytology ; Humans ; Mass Screening/*methods ; Occult Blood ; }, abstract = {PURPOSE: We report an update of current methods for colorectal cancer (CRC) screening based on fecal sample analysis.<br><br>METHODS: A systematic review of the literature was performed in MEDLINE, EMBASE, and Science Direct electronic databases.<br><br>RESULTS: Blood in the stools is the first and most used strategy. Fecal occult blood test (FOBT) and fecal immunochemical test (FIT) are the main methods. Both are economic, easy to perform with high specificity, and low sensitivity. Based on CRC multi-step process with genetic and epigenetic alterations in large bowel cell DNA, single mutations or panels of alterations have been detected. These tests have the advantage of a marked improvement of the sensitivity when compared to fecal blood. However, high costs, poor availability, and correct choice of marker panel represent the major limits. A specific sDNA panel including aberrantly methylated BMP3 and NDRG4 promoter regions, mutant k-ras and &#x3b2;-actin (a reference gene for human DNA quantity), and an immunochemical assay for human hemoglobin has been recently approved by Food and Drug Administration. Novel promising biomarkers for CRC screening are represented by microRNAs (miRNAs), a group of 18-25 nucleotide non-coding RNA molecules that regulate gene expression. Reports on these fecal biomarkers are case-control studies, and each of them evaluates single miRNAs or multi-target panels. On the other hand, some fecal proteins have been studied as possible CRC screening markers, even though they demonstrated poor results. Finally, alterations of estrogen receptor-beta (i.e., dramatic reduction in the early stage of CRC) have been demonstrated in tissue samples.<br><br>CONCLUSIONS: Specific investigations are warranted in order to add further noninvasive markers to the panel of CRC screening tools.}, }
@article {pmid26921425, year = {2016}, author = {Shaughnessy, MK and Bobr, A and Kuskowski, MA and Johnston, BD and Sadowsky, MJ and Khoruts, A and Johnson, JR}, title = {Environmental Contamination in Households of Patients with Recurrent Clostridium difficile Infection.}, journal = {Applied and environmental microbiology}, volume = {82}, number = {9}, pages = {2686-2692}, pmid = {26921425}, issn = {1098-5336}, support = {T32 AI055433/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Clostridioides difficile/classification/genetics/*isolation &amp; purification ; Clostridium Infections/*epidemiology/*microbiology ; Cross-Sectional Studies ; Environmental Microbiology ; Environmental Pollution/*statistics &amp; numerical data ; *Family Characteristics ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Minnesota/epidemiology ; Pets/microbiology ; Prevalence ; Recurrence ; Young Adult ; }, abstract = {Recurrent Clostridium difficile infection (R-CDI) is common and difficult to treat, potentially necessitating fecal microbiota transplantation (FMT). Although C. difficilespores persist in the hospital environment and cause infection, little is known about their potential presence or importance in the household environment. Households of R-CDI subjects in the peri-FMT period and of geographically matched and age-matched controls were analyzed for the presence ofC. difficile Household environmental surfaces and fecal samples from humans and pets in the household were examined. Households of post-FMT subjects were also examined (environmental surfaces only). Participants were surveyed regarding their personal history and household cleaning habits. Species identity and molecular characteristics of presumptive C. difficile isolates from environmental and fecal samples were determined by using the Pro kit (Remel, USA), Gram staining, PCR, toxinotyping, tcdC gene sequencing, and pulsed-field gel electrophoresis (PFGE). Environmental cultures detected C. difficile on ≥1 surface in 8/8 (100%) peri-FMT households, versus 3/8 (38%) post-FMT households and 3/8 (38%) control households (P= 0.025). The most common C. difficile-positive sites were the vacuum (11/27; 41%), toilet (8/30; 27%), and bathroom sink (5/29; 17%).C. difficile was detected in 3/36 (8%) fecal samples (two R-CDI subjects and one household member). Nine (90%) of 10 households with multiple C. difficile-positive samples had a single genotype present each. In conclusion,C. difficile was found in the household environment of R-CDI patients, but whether it was found as a cause or consequence of R-CDI is unknown. If household contamination leads to R-CDI, effective decontamination may be protective.}, }
@article {pmid26912898, year = {2016}, author = {Blanton, LV and Charbonneau, MR and Salih, T and Barratt, MJ and Venkatesh, S and Ilkaveya, O and Subramanian, S and Manary, MJ and Trehan, I and Jorgensen, JM and Fan, YM and Henrissat, B and Leyn, SA and Rodionov, DA and Osterman, AL and Maleta, KM and Newgard, CB and Ashorn, P and Dewey, KG and Gordon, JI}, title = {Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children.}, journal = {Science (New York, N.Y.)}, volume = {351}, number = {6275}, pages = {}, pmid = {26912898}, issn = {1095-9203}, support = {R01 DK030292/DK/NIDDK NIH HHS/United States ; T32 AI007172/AI/NIAID NIH HHS/United States ; P30 AR057235/AR/NIAMS NIH HHS/United States ; T32 GM007067/GM/NIGMS NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*classification ; Bifidobacterium/physiology ; Body Weight ; Bone Development ; Clostridiales/physiology ; Disease Models, Animal ; Feces/microbiology ; Femur/growth &amp; development ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Humans ; Infant ; Infant Nutrition Disorders/metabolism/*microbiology ; Malawi ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {Undernourished children exhibit impaired development of their gut microbiota. Transplanting microbiota from 6- and 18-month-old healthy or undernourished Malawian donors into young germ-free mice that were fed a Malawian diet revealed that immature microbiota from undernourished infants and children transmit impaired growth phenotypes. The representation of several age-discriminatory taxa in recipient animals correlated with lean body mass gain; liver, muscle, and brain metabolism; and bone morphology. Mice were cohoused shortly after receiving microbiota from healthy or severely stunted and underweight infants; age- and growth-discriminatory taxa from the microbiota of the former were able to invade that of the latter, which prevented growth impairments in recipient animals. Adding two invasive species, Ruminococcus gnavus and Clostridium symbiosum, to the microbiota from undernourished donors also ameliorated growth and metabolic abnormalities in recipient animals. These results provide evidence that microbiota immaturity is causally related to undernutrition and reveal potential therapeutic targets and agents.}, }
@article {pmid26908719, year = {2016}, author = {Vehreschild, MJ and Cornely, OA}, title = {Fecal Microbiota Transfer 2.0.}, journal = {The Journal of infectious diseases}, volume = {214}, number = {2}, pages = {169-170}, pmid = {26908719}, issn = {1537-6613}, support = {UM1 AI104681/AI/NIAID NIH HHS/United States ; }, mesh = {Clostridioides difficile ; Clostridium Infections ; *Feces ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; }, }
@article {pmid26908008, year = {2016}, author = {De Salvo, C and Wang, XM and Pastorelli, L and Mattioli, B and Omenetti, S and Buela, KA and Chowdhry, S and Garg, RR and Goodman, WA and Rodriguez-Palacios, A and Smith, DE and Abbott, DW and Cominelli, F and Bamias, G and Xin, W and Lee, JJ and Vecchi, M and Pizarro, TT}, title = {IL-33 Drives Eosinophil Infiltration and Pathogenic Type 2 Helper T-Cell Immune Responses Leading to Chronic Experimental Ileitis.}, journal = {The American journal of pathology}, volume = {186}, number = {4}, pages = {885-898}, pmid = {26908008}, issn = {1525-2191}, support = {R21 AI102269/AI/NIAID NIH HHS/United States ; DK056762/DK/NIDDK NIH HHS/United States ; DK097948/DK/NIDDK NIH HHS/United States ; P01 DK091222/DK/NIDDK NIH HHS/United States ; R01 DK056762/DK/NIDDK NIH HHS/United States ; R37 DK042191/DK/NIDDK NIH HHS/United States ; DK042191/DK/NIDDK NIH HHS/United States ; K01 DK105138/DK/NIDDK NIH HHS/United States ; DK055812/DK/NIDDK NIH HHS/United States ; DK091222/DK/NIDDK NIH HHS/United States ; P30 DK097948/DK/NIDDK NIH HHS/United States ; AI102269/AI/NIAID NIH HHS/United States ; R01 GM086550/GM/NIGMS NIH HHS/United States ; R56 DK042191/DK/NIDDK NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; R56 DK055812/DK/NIDDK NIH HHS/United States ; R01 DK055812/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cytokines/metabolism ; Disease Models, Animal ; Eosinophils/*cytology ; Ileitis/immunology/*pathology ; Inflammation/immunology/metabolism ; Interleukin-33/*metabolism ; Intestinal Mucosa/metabolism ; Mice ; Th2 Cells/*immunology ; Up-Regulation ; }, abstract = {Although a clear association has been established between IL-33 and inflammatory bowel disease, mechanistic studies to date, primarily using acute murine models of colitis, have yielded contradicting results, demonstrating both pathogenic and protective roles. We used a well-characterized, spontaneous model of inflammatory bowel disease [ie, SAMP1/YitFc (SAMP) mice] to investigate the role of IL-33 during chronic intestinal inflammation. Our results showed marked eosinophil infiltration into the gut mucosa with increased levels of eotaxins and type 2 helper T-cell (Th2) cytokines as disease progressed and became more severe, which could be reversed upon either eosinophil depletion or blockade of IL-33 signaling. Exogenous IL-33 administration recapitulated these effects in ilea of uninflamed (parental) control AKR/J mice. Human data supported these findings, showing colocalization and up-regulation of IL-33 and eosinophils in the colonic mucosa of inflammatory bowel disease patients versus noninflamed controls. Finally, colonization of commensal flora by fecal material transplantation into germ-free SAMP and the presence of the gut microbiome induced IL-33, subsequent eosinophil infiltration, and mounting of Th2 immune responses, leading to exacerbation of chronic intestinal inflammation characteristic of SAMP mice. These data demonstrate a pathogenic role for IL-33-mediated eosinophilia and activation of Th2 immunity in chronic intestinal inflammation that is dependent on the gut microbiome. Targeting IL-33 may represent a novel therapeutic approach to treat patients with inflammatory bowel disease.}, }
@article {pmid26906406, year = {2016}, author = {Banerjee, S and Sindberg, G and Wang, F and Meng, J and Sharma, U and Zhang, L and Dauer, P and Chen, C and Dalluge, J and Johnson, T and Roy, S}, title = {Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation.}, journal = {Mucosal immunology}, volume = {9}, number = {6}, pages = {1418-1428}, pmid = {26906406}, issn = {1935-3456}, support = {R01 DA012104/DA/NIDA NIH HHS/United States ; R01 DA037843/DA/NIDA NIH HHS/United States ; R01 DA034582/DA/NIDA NIH HHS/United States ; R01 DA022935/DA/NIDA NIH HHS/United States ; R01 DA031202/DA/NIDA NIH HHS/United States ; T32 DA007097/DA/NIDA NIH HHS/United States ; P50 DA011806/DA/NIDA NIH HHS/United States ; R21 HL125021/HL/NHLBI NIH HHS/United States ; K05 DA033881/DA/NIDA NIH HHS/United States ; }, mesh = {Analgesics, Opioid/*pharmacology ; Animals ; Bile/*metabolism ; Bile Acids and Salts/metabolism ; Cholesterol/metabolism ; *Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Immune System/immunology/metabolism ; Immunity, Mucosal ; Inflammation/*etiology/*metabolism ; Intestinal Mucosa/*drug effects/immunology/*metabolism/*microbiology ; Liver/drug effects/immunology/metabolism ; Mice ; Mice, Knockout ; Morphine/pharmacology ; Receptors, Opioid, mu/metabolism ; Toll-Like Receptor 2/metabolism ; }, abstract = {Morphine and its pharmacological derivatives are the most prescribed analgesics for moderate to severe pain management. However, chronic use of morphine reduces pathogen clearance and induces bacterial translocation across the gut barrier. The enteric microbiome has been shown to have a critical role in the preservation of the mucosal barrier function and metabolic homeostasis. Here, we show for the first time, using bacterial 16s rDNA sequencing, that chronic morphine treatment significantly alters the gut microbial composition and induces preferential expansion of Gram-positive pathogenic and reduction in bile-deconjugating bacterial strains. A significant reduction in both primary and secondary bile acid levels was seen in the gut, but not in the liver with morphine treatment. Morphine-induced microbial dysbiosis and gut barrier disruption was rescued by transplanting placebo-treated microbiota into morphine-treated animals, indicating that microbiome modulation could be exploited as a therapeutic strategy for patients using morphine for pain management.}, }
@article {pmid26906189, year = {2016}, author = {Petterson, J and York, V and Ward, P and Green, N and She, R}, title = {The value of a multiplexed gastrointestinal pathogen panel in 2 distinct patient populations.}, journal = {Diagnostic microbiology and infectious disease}, volume = {85}, number = {1}, pages = {105-108}, doi = {10.1016/j.diagmicrobio.2015.12.020}, pmid = {26906189}, issn = {1879-0070}, mesh = {Adult ; Aged ; Aged, 80 and over ; Feces/microbiology/virology ; Female ; Gastroenteritis/diagnosis/*microbiology/*virology ; Humans ; Male ; Middle Aged ; Molecular Diagnostic Techniques/*methods ; Sensitivity and Specificity ; Young Adult ; }, abstract = {We assess the value of the Luminex xTAG Gastrointestinal Pathogen Panel (GPP) in 2 different patient populations: an uninsured, indigent population seeking primary care, and a tertiary care hospital specializing in surgical, transplant, and oncology care. Stool specimens collected April to August 2013 for infectious workup were tested on the GPP, and discordant results were further analyzed by alternative methods. Compared to the tertiary care setting, stool pathogen detection was nearly twice as frequent in the primary care setting (25% versus 14%; P<0.05) with a broader array of pathogens detected (15 versus 4). Overall, the greatest value of the GPP was in detection of viral causes of gastroenteritis that were not routinely sought and in detection of Campylobacter spp. when patients presented late in the disease course. Application of a GPP should consider the characteristics of the patient population to maximize its clinical utility in different healthcare settings.}, }
@article {pmid26905904, year = {2016}, author = {Khoruts, A and Rank, KM and Newman, KM and Viskocil, K and Vaughn, BP and Hamilton, MJ and Sadowsky, MJ}, title = {Inflammatory Bowel Disease Affects the Outcome of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {14}, number = {10}, pages = {1433-1438}, pmid = {26905904}, issn = {1542-7714}, support = {L30 DK099831/DK/NIDDK NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*complications/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Hospitals, University ; Humans ; Inflammatory Bowel Diseases/*complications ; Male ; Middle Aged ; Minnesota ; Prospective Studies ; Retrospective Studies ; Secondary Prevention ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: A significant fraction of patients with recurrent Clostridium difficile infections (CDI) have inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) can break the cycle of CDI recurrence and can be performed without evaluation of the colon. We evaluated the efficacy of colonoscopic FMT in patients with and without IBD, and whether we could identify IBD in patients during this procedure.<br><br>METHODS: We collected clinical meta-data and colonoscopy results from 272 consecutive patients that underwent FMT for recurrent CDI at the University of Minnesota from 2008 through 2015. Patients had at least 2 spontaneous relapses of CDI following their initial episode and did not clear the infection after 1 extended antibiotic regimen. We collected random mucosal biopsies from patients' right colons to identify lymphocytic or collagenous colitis during the FMT procedure. Failure or success in clearing CDI was determined within or at 2 months after the FMT.<br><br>RESULTS: Of patients undergoing FMT, 15% had established IBD and 2.6% were found to have IBD during the FMT procedure. A single colonoscopic FMT cleared CDI from 74.4% of patients with IBD and 92.1% of patients without IBD (P&#xa0;= .0018). Patients had similar responses to FMT regardless of immunosuppressive therapy. More than one-quarter of patients with IBD (25.6%) had a clinically significant flare of IBD after FMT. Lymphocytic colitis was documented in 7.4% of patients with endoscopically normal colon mucosa; only 3 of these patients (20%) required additional treatment for colitis after clearance of CDI.<br><br>CONCLUSIONS: Based on an analysis of 272 patients, FMT is somewhat less effective in clearing recurrent CDI from patients with IBD, compared with patients without IBD, regardless of immunosuppressive therapy. More than 25% of patients with IBD have a disease flare following FMT. Lymphocytic colitis did not affect the outcome of FMT, but a small fraction of these patients required pharmacologic treatment after the procedure.}, }
@article {pmid26905790, year = {2016}, author = {Halpin, AL and de Man, TJ and Kraft, CS and Perry, KA and Chan, AW and Lieu, S and Mikell, J and Limbago, BM and McDonald, LC}, title = {Intestinal microbiome disruption in patients in a long-term acute care hospital: A case for development of microbiome disruption indices to improve infection prevention.}, journal = {American journal of infection control}, volume = {44}, number = {7}, pages = {830-836}, pmid = {26905790}, issn = {1527-3296}, support = {CC999999//Intramural CDC HHS/United States ; P30 AI050409/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/*classification/genetics ; Cluster Analysis ; Cross-Sectional Studies ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Diarrhea/microbiology ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Hospitals ; Humans ; Long-Term Care ; Male ; *Microbiota ; Middle Aged ; Phylogeny ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Composition and diversity of intestinal microbial communities (microbiota) are generally accepted as a risk factor for poor outcomes; however, we cannot yet use this information to prevent adverse outcomes.<br><br>METHODS: Stool was collected from 8 long-term acute care hospital patients experiencing diarrhea and 2 fecal microbiota transplant donors; 16S rDNA V1-V2 hypervariable regions were sequenced. Composition and diversity of each sample were described. Stool was also tested for Clostridium difficile, vancomycin-resistant enterococci (VRE), and carbapenem-resistant Enterobacteriaceae. Associations between microbiota diversity and demographic and clinical characteristics, including antibiotic use, were analyzed.<br><br>RESULTS: Antibiotic exposure and Charlson Comorbidity Index were inversely correlated with diversity (Spearman&#x2009;=&#x2009;-0.7). Two patients were positive for VRE; both had microbiomes dominated by Enterococcus faecium, accounting for 67%-84% of their microbiome.<br><br>CONCLUSIONS: Antibiotic exposure correlated with diversity; however, other environmental and host factors not easily obtainable in a clinical setting are also known to impact the microbiota. Therefore, direct measurement of microbiome disruption by sequencing, rather than reliance on surrogate markers, might be most predictive of adverse outcomes. If and when microbiome characterization becomes a standard diagnostic test, improving our understanding of microbiome dynamics will allow for interpretation of results to improve patient outcomes.}, }
@article {pmid26901316, year = {2016}, author = {Lapointe-Shaw, L and Tran, KL and Coyte, PC and Hancock-Howard, RL and Powis, J and Poutanen, SM and Hota, S}, title = {Cost-Effectiveness Analysis of Six Strategies to Treat Recurrent Clostridium difficile Infection.}, journal = {PloS one}, volume = {11}, number = {2}, pages = {e0149521}, pmid = {26901316}, issn = {1932-6203}, mesh = {Anti-Bacterial Agents/administration &amp; dosage/*economics ; Canada ; *Clostridioides difficile ; Costs and Cost Analysis ; Enterocolitis, Pseudomembranous/*economics/therapy ; Fecal Microbiota Transplantation/*economics ; Female ; Humans ; Male ; }, abstract = {OBJECTIVE: To assess the cost-effectiveness of six treatment strategies for patients diagnosed with recurrent Clostridium difficile infection (CDI) in Canada: 1. oral metronidazole; 2. oral vancomycin; 3.oral fidaxomicin; 4. fecal transplantation by enema; 5. fecal transplantation by nasogastric tube; and 6. fecal transplantation by colonoscopy.<br><br>PERSPECTIVE: Public insurer for all hospital and physician services.<br><br>SETTING: Ontario, Canada.<br><br>METHODS: A decision analytic model was used to model costs and lifetime health effects of each strategy for a typical patient experiencing up to three recurrences, over 18 weeks. Recurrence data and utilities were obtained from published sources. Cost data was obtained from published sources and hospitals in Toronto, Canada. The willingness-to-pay threshold was $50,000/QALY gained.<br><br>RESULTS: Fecal transplantation by colonoscopy dominated all other strategies in the base case, as it was less costly and more effective than all alternatives. After accounting for uncertainty in all model parameters, there was an 87% probability that fecal transplantation by colonoscopy was the most beneficial strategy. If colonoscopy was not available, fecal transplantation by enema was cost-effective at $1,708 per QALY gained, compared to metronidazole. In addition, fecal transplantation by enema was the preferred strategy if the probability of recurrence following this strategy was below 8.7%. If fecal transplantation by any means was unavailable, fidaxomicin was cost-effective at an additional cost of $25,968 per QALY gained, compared to metronidazole.<br><br>CONCLUSION: Fecal transplantation by colonoscopy (or enema, if colonoscopy is unavailable) is cost-effective for treating recurrent CDI in Canada. Where fecal transplantation is not available, fidaxomicin is also cost-effective.}, }
@article {pmid26900286, year = {2016}, author = {Distrutti, E and Monaldi, L and Ricci, P and Fiorucci, S}, title = {Gut microbiota role in irritable bowel syndrome: New therapeutic strategies.}, journal = {World journal of gastroenterology}, volume = {22}, number = {7}, pages = {2219-2241}, pmid = {26900286}, issn = {2219-2840}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bacteria/*growth &amp; development ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology ; Irritable Bowel Syndrome/diagnosis/*microbiology/therapy ; Prebiotics ; Probiotics/therapeutic use ; Synbiotics ; Treatment Outcome ; }, abstract = {In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.}, }
@article {pmid29067183, year = {2016}, author = {Craig, JM}, title = {Atopic dermatitis and the intestinal microbiota in humans and dogs.}, journal = {Veterinary medicine and science}, volume = {2}, number = {2}, pages = {95-105}, pmid = {29067183}, issn = {2053-1095}, abstract = {The prevalence of human and canine allergic diseases is commonly perceived to be increasing. Suggested predisposing factors in people and dogs include increased allergen load, increased exposure to pollutants, reduced family size, reduced microbial load and less exposure to infection at a young age, increasingly urbanised environment, and changes in dietary habits. Genetic make-up may provide a template for phenotypic predisposition which is strongly influenced by our diet and environment leading to constant regulation of gene expression. One way in which diet can alter gene expression is via its effects on the gut flora or microbiota, the collection of microbes residing in the gastrointestinal tract. The resident microbiota is important in maintaining structural and functional integrity of the gut and in immune system regulation. It is an important driver of host immunity, helps protect against invading enteropathogens, and provides nutritional benefits to the host. Disruption of the microbiota (dysbiosis) may lead to severe health problems, both in the gastrointestinal tract and extra-intestinal organ systems. The precise mechanisms by which the intestinal microbiota exerts its effects are only beginning to be unravelled but research is demonstrating close links between gut microflora and many factors involved in the pathogenesis of atopic dermatitis (AD). AD and indeed any other 'skin disease', may be seen as a possible manifestation of a more systemic problem involving gut dysbiosis and increased intestinal permeability, which may occur even in the absence of gastrointestinal signs. Manipulation of the canine intestinal microbiota as a method for modifying atopy, may be attempted in many ways including avoidance of certain foods, supplementation with probiotics and prebiotics, optimising nutrient intake, minimising stress, antimicrobial therapy, correction and prevention of low stomach acid, and faecal microbiota transplantation (FMT).}, }
@article {pmid26890327, year = {2016}, author = {Waye, A and Atkins, K and Kao, D}, title = {Cost Averted With Timely Fecal Microbiota Transplantation in the Management of Recurrent Clostridium difficile Infection in Alberta, Canada.}, journal = {Journal of clinical gastroenterology}, volume = {50}, number = {9}, pages = {747-753}, doi = {10.1097/MCG.0000000000000494}, pmid = {26890327}, issn = {1539-2031}, mesh = {Aged ; Alberta/epidemiology ; Clostridium Infections/*epidemiology/microbiology/therapy ; *Cost Savings ; Databases, Factual ; Fecal Microbiota Transplantation/economics/*statistics &amp; numerical data ; Female ; Humans ; Length of Stay ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective in treating recurrent Clostridium difficile infection (RCDI). However, the ideal timing for offering FMT remains to be determined. Furthermore, the direct medical costs averted with timely FMT have not been examined.<br><br>METHODS: A retrospective review of the Edmonton FMT program database included patients who received FMT for RCDI (October 2012 to September 2014). They were divided into 2 groups: those who received FMT after 2 recurrences (the timely FMT group) and those who received FMT after at least 3 recurrences (the delayed FMT group). The primary outcome was the difference in direct medical costs related to hospital admissions and emergency room visits due to CDI between the 2 groups. The secondary outcomes were RCDI cure rate and duration of RCDI in each group.<br><br>RESULTS: A total of 75 patients were included: 30 received timely FMT, whereas 45 received delayed FMT. The mean difference in hospital length of stay and emergency room visits related to CDI were 13.8 days shorter and 1.3 visits fewer with timely FMT, associated with a mean cost saving of $29,842 per patient. Sensitivity analysis was performed to examine the effect of outliers and comorbities on the differential costs, and it was found that the differences in average cost per patient were more pronounced in those with Charlson comorbidity index &#x2265;3 compared with those with scores of 0 to 2. The cure rate was 94% (timely FMT group) and 93% (delayed FMT group). The mean duration of RCDI was 109 days (timely FMT group) and 281 days (delayed FMT group).<br><br>CONCLUSIONS: Timely FMT can provide significant cost savings to health-care systems, especially for patients with multiple comorbidities.}, }
@article {pmid26889028, year = {2016}, author = {van de Garde, MD and Pas, SD and van der Net, G and de Man, RA and Osterhaus, AD and Haagmans, BL and Boonstra, A and Vanwolleghem, T}, title = {Hepatitis E Virus (HEV) Genotype 3 Infection of Human Liver Chimeric Mice as a Model for Chronic HEV Infection.}, journal = {Journal of virology}, volume = {90}, number = {9}, pages = {4394-4401}, pmid = {26889028}, issn = {1098-5514}, mesh = {Animals ; Cell Line ; Chronic Disease ; Disease Models, Animal ; *Genotype ; Hepatitis E/*virology ; Hepatitis E virus/*genetics/metabolism ; Hepatocytes/transplantation/virology ; Host-Pathogen Interactions ; Humans ; Mice ; Viral Load ; Virus Replication ; }, abstract = {UNLABELLED: Genotype 3 (gt3) hepatitis E virus (HEV) infections are emerging in Western countries. Immunosuppressed patients are at risk of chronic HEV infection and progressive liver damage, but no adequate model system currently mimics this disease course. Here we explore the possibilities of in vivo HEV studies in a human liver chimeric mouse model (uPA(+/+)Nod-SCID-IL2Rγ(-/-)) next to the A549 cell culture system, using HEV RNA-positive EDTA-plasma, feces, or liver biopsy specimens from 8 immunocompromised patients with chronic gt3 HEV. HEV from feces- or liver-derived inocula showed clear virus propagation within 2 weeks after inoculation onto A549 cells, compared to slow or no HEV propagation of HEV RNA-positive, EDTA-plasma samples. These in vitro HEV infectivity differences were mirrored in human-liver chimeric mice after intravenous (i.v.) inoculation of selected samples. HEV RNA levels of up to 8 log IU HEV RNA/gram were consistently present in 100% of chimeric mouse livers from week 2 to week 14 after inoculation with human feces- or liver-derived HEV. Feces and bile of infected mice contained moderate to large amounts of HEV RNA, while HEV viremia was low and inconsistently detected. Mouse-passaged HEV could subsequently be propagated for up to 100 days in vitro In contrast, cell culture-derived or seronegative EDTA-plasma-derived HEV was not infectious in inoculated animals. In conclusion, the infectivity of feces-derived human HEV is higher than that of EDTA-plasma-derived HEV both in vitro and in vivo Persistent HEV gt3 infections in chimeric mice show preferential viral shedding toward mouse bile and feces, paralleling the course of infection in humans.<br><br>IMPORTANCE: Hepatitis E virus (HEV) genotype 3 infections are emerging in Western countries and are of great concern for immunosuppressed patients at risk for developing chronic HEV infection. Lack of adequate model systems for chronic HEV infection hampers studies on HEV infectivity and transmission and antiviral drugs. We compared the in vivo infectivity of clinical samples from chronic HEV patients in human liver chimeric mice to an in vitro virus culture system. Efficient in vivo HEV infection is observed after inoculation with feces- and liver-derived HEV but not with HEV RNA-containing plasma or cell culture supernatant. HEV in chimeric mice is preferentially shed toward bile and feces, mimicking the HEV infection course in humans. The observed in vivo infectivity differences may be relevant for the epidemiology of HEV in humans. This novel small-animal model therefore offers new avenues to unravel HEV's pathobiology.}, }
@article {pmid26888731, year = {2016}, author = {Park, EJ and Kang, J and Baik, SH}, title = {Treatment of faecal incontinence using allogeneic-adipose-derived mesenchymal stem cells: a study protocol for a pilot randomised controlled trial.}, journal = {BMJ open}, volume = {6}, number = {2}, pages = {e010450}, pmid = {26888731}, issn = {2044-6055}, mesh = {Adipose Tissue ; Fecal Incontinence/*therapy ; Humans ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Pilot Projects ; Prospective Studies ; *Research Design ; Single-Blind Method ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {INTRODUCTION: Faecal incontinence is a distressing condition with recurrent uncontrolled passage of faecal material. Although faecal incontinence may cause psychological depression and social isolation, previous treatments have been limited. Recently, regenerative treatment has been developed using mesenchymal stem cells. Especially, there are possibilities that adipose-tissue-derived stem cells can be effective to treat a degenerated anal sphincter that is causing faecal incontinence. Therefore, this study aimed to investigate the safety and efficacy of using allogeneic-adipose-derived mesenchymal stem cells in the treatment of the anal sphincter of patients with faecal incontinence.<br><br>METHODS AND ANALYSIS: This study is a randomised, prospective, dose escalation, placebo-controlled, single-blinded, single-centre trial with two parallel groups. The safety test is performed by an injection of allogeneic-adipose-derived mesenchymal stem cells (ALLO-ASCs) into the anal sphincter with dose escalation (3 &#xd7; 10(7), 6 &#xd7; 10(7) and 9 &#xd7; 10(7) cells, sequentially). After confirming the safety of the stem cells, an efficacy test is performed by this dose in the experimental group. The experimental group will receive ALLO-ASCs mixed with fibrin glue into the anal sphincter, and the placebo group will receive 0.9% normal saline injection mixed with fibrin glue. The primary end point is to assess the safety of ALLO-ASCs after the injection into the anal sphincter, and the secondary end point is to compare the efficacy of ALLO-ASC injection with fibrin glue in patients with faecal incontinence.<br><br>ETHICS AND DISSEMINATION: The study protocol was approved by the Ministry of Food and Drug Safety and the Ministry of Health &amp; Welfare, in the Republic of Korea. The informed consent form was approved by the institutional review board of Gangnam Severance Hospital (IRB approval number 3-2014-0271). Dissemination of the results will be presented at a conference and in peer-reviewed publications.<br><br>TRIAL REGISTRATION NUMBER: NCT02384499; Pre-results.}, }
@article {pmid26887816, year = {2017}, author = {Kummen, M and Holm, K and Anmarkrud, JA and Nygård, S and Vesterhus, M and Høivik, ML and Trøseid, M and Marschall, HU and Schrumpf, E and Moum, B and Røsjø, H and Aukrust, P and Karlsen, TH and Hov, JR}, title = {The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls.}, journal = {Gut}, volume = {66}, number = {4}, pages = {611-619}, doi = {10.1136/gutjnl-2015-310500}, pmid = {26887816}, issn = {1468-3288}, mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; Case-Control Studies ; Cholangitis, Sclerosing/complications/drug therapy/*microbiology ; Colitis, Ulcerative/complications/*microbiology ; Cross-Sectional Studies ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; Prospective Studies ; RNA, Ribosomal, 16S/*analysis ; ROC Curve ; Severity of Illness Index ; Veillonella/*isolation &amp; purification ; Young Adult ; }, abstract = {OBJECTIVE: Gut microbiota could influence gut, as well as hepatic and biliary immune responses. We therefore thoroughly characterised the gut microbiota in primary sclerosing cholangitis (PSC) compared with healthy controls (HC) and patients with ulcerative colitis without liver disease.<br><br>DESIGN: We prospectively collected 543 stool samples. After a stringent exclusion process, bacterial DNA was submitted for 16S rRNA gene sequencing. PSC and HC were randomised to an exploration panel or a validation panel, and only significant results (p<0.05, QFDR<0.20) in both panels were reported, followed by a combined comparison of all samples against UC.<br><br>RESULTS: Patients with PSC (N=85) had markedly reduced bacterial diversity compared with HC (N=263, p<0.0001), and a different global microbial composition compared with both HC (p<0.001) and UC (N=36, p<0.01). The microbiota of patients with PSC with and without IBD was similar. Twelve genera separated PSC and HC, out of which 11 were reduced in PSC. However, the Veillonella genus showed a marked increase in PSC compared with both HC (p<0.0001) and UC (p<0.02). Using receiver operating characteristic analysis, Veillonella abundance yielded an area under the curve (AUC) of 0.64 to discriminate PSC from HC, while a combination of PSC-associated genera yielded an AUC of 0.78.<br><br>CONCLUSIONS: Patients with PSC exhibited a gut microbial signature distinct from both HC and UC without liver disease, but similar in PSC with and without IBD. The Veillonella genus, which is also associated with other chronic inflammatory and fibrotic conditions, was enriched in PSC.}, }
@article {pmid26886180, year = {2016}, author = {Harris, B and Morjaria, SM and Littmann, ER and Geyer, AI and Stover, DE and Barker, JN and Giralt, SA and Taur, Y and Pamer, EG}, title = {Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation.}, journal = {American journal of respiratory and critical care medicine}, volume = {194}, number = {4}, pages = {450-463}, pmid = {26886180}, issn = {1535-4970}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; UL1 TR000457/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; K23 AI095398/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Hematologic Neoplasms/complications/mortality/*surgery ; Hematopoietic Stem Cell Transplantation/*adverse effects/mortality ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Diseases/*etiology/microbiology/mortality ; Male ; Middle Aged ; Predictive Value of Tests ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Transplantation, Homologous/adverse effects/mortality ; }, abstract = {RATIONALE: Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown.<br><br>OBJECTIVES: To investigate whether changes in gut microbiota are associated with PCs after HCT.<br><br>METHODS: A single-center observational study was performed on 94 patients who underwent HCT from 2009 to 2011 and who were previously enrolled in a protocol for 16S ribosomal RNA sequencing of fecal microbiota. The primary endpoint, PC, was defined by new abnormal parenchymal findings on chest imaging in the setting of respiratory signs and/or symptoms. Outcomes were collected up to 40 months after transplant. Clinical and microbiota risk factors for PCs and mortality were evaluated using survival analysis.<br><br>MEASUREMENTS AND MAIN RESULTS: One hundred twelve PCs occurred in 66 (70.2%) subjects. A high comorbidity index (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.30-4.00; P&#x2009;=&#x2009;0.004), fluoroquinolones (HR, 2.29, 95% CI, 1.32-3.98; P&#x2009;=&#x2009;0.003), low baseline diversity (HR, 2.63; 95% CI, 1.22-5.32; P&#x2009;=&#x2009;0.015), and &#x3b3;-proteobacteria domination of fecal microbiota (HR, 2.64; 95% CI, 1.10-5.65; P&#x2009;=&#x2009;0.031), which included common respiratory pathogens, predicted PCs. In separate analyses, low baseline diversity was associated with PCs that occurred preengraftment (HR, 6.30; 95% CI, 1.42-31.80; P&#x2009;=&#x2009;0.016), whereas &#x3b3;-proteobacteria domination predicted PCs postengraftment (HR, 3.68; 95% CI, 1.49-8.21; P&#x2009;=&#x2009;0.006) and overall mortality (HR, 3.52; 95% CI, 1.28-9.21; P&#x2009;=&#x2009;0.016). Postengraftment PCs were also independent predictors of death (HR, 2.50; 95% CI, 1.25-5.22; P&#x2009;=&#x2009;0.009).<br><br>CONCLUSIONS: This is the first study to demonstrate prospective changes in gut microbiota associated with PCs after HCT. Postengraftment PCs and &#x3b3;-proteobacteria domination were predictive of mortality. This suggests an adverse relationship between the graft and lung, which is perhaps mediated by bacterial composition in the gut. Further study is warranted.}, }
@article {pmid26884739, year = {2016}, author = {Shin, JY and Ko, EJ and Lee, SH and Shin, JB and Kim, SI and Kwon, KS and Kim, HG and Shin, YW and Bang, BW}, title = {Refractory pseudomembranous colitis that was treated successfully with colonoscopic fecal microbial transplantation.}, journal = {Intestinal research}, volume = {14}, number = {1}, pages = {83-88}, pmid = {26884739}, issn = {1598-9100}, abstract = {Pseudomembranous colitis (PMC) is a nosocomial and opportunistic infection caused by Clostridium difficile. PMC is related to the use of antibiotics leading to intestinal dysbiosis and an overgrowth of C. difficile. Metronidazole or vancomycin is considered to be the standard therapy for the management of PMC. However, PMC has a 15%-30% recurrence rate and can be refractory to standard treatments, resulting in morbidity and mortality. Here we describe a patient who experienced refractory PMC who was treated with fecal microbiota transplantation. A 69-year-old woman was admitted to the hospital with consistent abdominal pain and diarrhea, which had been present for 5 months. She was diagnosed with PMC by colonoscopy and tested positive for C. difficile toxin. Even though she took metronidazole for 10 days, followed by vancomycin for 4 weeks, her symptoms did not improve. Because of her recurrent and refractory symptoms, we decided to perform fecal microbiota transplantation. Fifty grams of fresh feces from a donor were obtained on the day of the procedure, mixed with 500 mL of normal saline, and then filtered. The filtered solution was administered to the patient's colon using a colonoscope. After the procedure, her symptoms rapidly improved and a follow-up colonoscopy showed that the PMC had resolved without recurrence.}, }
@article {pmid26880781, year = {2016}, author = {Gómez-Junyent, J and Paredes-Zapata, D and de las Parras, ER and González-Costello, J and Ruiz-Arranz, &#xc1; and Cañizares, R and Saugar, JM and Muñoz, J}, title = {Real-Time Polymerase Chain Reaction in Stool Detects Transmission of Strongyloides stercoralis from an Infected Donor to Solid Organ Transplant Recipients.}, journal = {The American journal of tropical medicine and hygiene}, volume = {94}, number = {4}, pages = {897-899}, pmid = {26880781}, issn = {1476-1645}, mesh = {Aged ; Animals ; Fatal Outcome ; Feces/*parasitology ; Female ; Heart Transplantation/*adverse effects ; Humans ; Liver Transplantation/*adverse effects ; Male ; Middle Aged ; Real-Time Polymerase Chain Reaction ; *Strongyloides stercoralis ; Strongyloidiasis/*diagnosis/transmission ; Tissue Donors ; }, abstract = {Solid organ transplant recipients can acquire Strongyloides stercoralis from an infected donor. The diagnosis of S. stercoralis in immunocompromised individuals may be challenging due to a lower sensitivity of available parasitological and serological methods, compared with immunocompetent individuals. Recently, a real-time polymerase chain reaction (RT-PCR) in stool has been developed for S. stercoralis diagnosis. We report two cases of S. stercoralis infection transmitted by a donor to two solid organ transplant recipients, who were diagnosed with RT-PCR in stool. This test could play an important role inS. stercoralis diagnosis in immunosuppressed patients, facilitating rapid treatment initiation and reducing the risk of severe strongyloidiasis. Adherence to current recommendations of screening among donors and recipients from endemic areas is also urgently needed.}, }
@article {pmid26876964, year = {2016}, author = {Wright, B and Emmanuel, A and Athanasakos, E and Parmar, N and Parker, G and Green, B and Tailby, E and Chandler, H and Cushnie, J and Pembroke, J and Saruchera, Y and Vashisht, A and Day, R}, title = {Women's views on autologous cell-based therapy for post-obstetric incontinence.}, journal = {Regenerative medicine}, volume = {11}, number = {2}, pages = {169-180}, doi = {10.2217/rme.15.88}, pmid = {26876964}, issn = {1746-076X}, support = {MR/L002752/1//Medical Research Council/United Kingdom ; }, mesh = {Adult ; *Attitude to Health ; Autografts ; *Cell- and Tissue-Based Therapy ; Fecal Incontinence/etiology/*therapy ; Female ; Humans ; *Postpartum Period ; *Surveys and Questionnaires ; Urinary Incontinence/etiology/*therapy ; }, abstract = {AIM: Fecal and urinary incontinence are devastating consequences of obstetric-related perineal injury. The aim of the present study is to determine acceptability to parous women of autologous cell-based therapy for fecal and urinary incontinence that arises due to pelvic diaphragm tearing during vaginal childbirth.<br><br>MATERIALS &amp; METHODS: A multiple choice questionnaire survey was offered to 76 parous women at the Maternity Unit, University College Hospital, London, UK. Seventy completed questionnaires - response rate: 92%.<br><br>RESULTS: In total, 84% of women indicated a willingness to accept autologous cell-based therapy for obstetric injury-induced incontinence rather than surgery.<br><br>CONCLUSION: These observational data provide an indication of likely acceptance of autologous cell-based therapies for birth injury incontinence and will help with designing new therapeutic approaches.}, }
@article {pmid26874932, year = {2016}, author = {Mika, A and Stepnowski, P}, title = {Current methods of the analysis of immunosuppressive agents in clinical materials: A review.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {127}, number = {}, pages = {207-231}, doi = {10.1016/j.jpba.2016.01.059}, pmid = {26874932}, issn = {1873-264X}, mesh = {Chromatography, High Pressure Liquid/*methods ; Drug Monitoring/instrumentation/*methods ; Feces/chemistry ; Gas Chromatography-Mass Spectrometry/*methods ; Humans ; Immunoassay/*methods ; Immunosuppressive Agents/*analysis/blood/urine ; Inactivation, Metabolic ; Organ Specificity ; Tissue Distribution ; }, abstract = {More than 100000 solid organ transplantations are performed every year worldwide. Calcineurin (cyclosporine A, tacrolimus), serine/threonine kinase (sirolimus, everolimus) and inosine monophosphate dehydrogenase inhibitor (mycophenolate mofetil), are the most common drugs used as immunosuppressive agents after solid organ transplantation. Immunosuppressive therapy, although necessary after transplantation, is associated with many adverse consequences, including the formation of secondary metabolites of drugs and the induction of their side effects. Calcineurin inhibitors are associated with nephrotoxicity, cardiotoxicity and neurotoxicity; moreover, they increase the risk of many diseases after transplantation. The review presents a study of the movement of drugs in the body, including the processes of absorption, distribution, localisation in tissues, biotransformation and excretion, and also their accompanying side effects. Therefore, there is a necessity to monitor immunosuppressants, especially because these drugs are characterised by narrow therapeutic ranges. Their incorrect concentrations in a patient's blood could result in transplant rejection or in the accumulation of toxic effects. Immunosuppressive pharmaceuticals are macrolide lactones, peptides, and high molecular weight molecules that can be metabolised to several metabolites. Therefore the two main analytical methods used for their determination are high performance liquid chromatography with various detection methods and immunoassay methods. Despite the rapid development of new analytical methods of analysing immunosuppressive agents, the application of the latest generation of detectors and increasing sensitivity of such methods, there is still a great demand for the development of highly selective, sensitive, specific, rapid and relatively simple methods of immunosuppressive drugs analysis.}, }
@article {pmid26871249, year = {2016}, author = {Huang, Y and Wang, X and Li, X and Peng, N}, title = {Successful Fecal Bacteria Transplantation and Nurse Management for a Patient With Intractable Functional Constipation: A Case Study.}, journal = {Holistic nursing practice}, volume = {30}, number = {2}, pages = {116-121}, doi = {10.1097/HNP.0000000000000134}, pmid = {26871249}, issn = {1550-5138}, mesh = {Constipation/*nursing/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Middle Aged ; }, abstract = {Intractable functional constipation is a common gastrointestinal disorder that features persistent difficult defecation, reduced bowel movements, or a feeling of incomplete defecation. Despite many therapeutic approaches, there has not been an established standard treatment protocol. Fecal microbiota transplantation (FMT), an innovative therapy that was introduced recently, has been preliminarily shown to have good effects and is expected to have good prospects. However, nursing is also of great importance during the process of FMT. An innovative nursing care protocol is combined with FMT, with a view to improving the clinical symptoms and quality of life of patients with intractable functional dyspepsia. This case-based study addresses the effects of nursing interventions used during the treatment of one patient with intractable functional constipation who received FMT.}, }
@article {pmid26870931, year = {2016}, author = {Anand, G and Zarrinpar, A and Loomba, R}, title = {Targeting Dysbiosis for the Treatment of Liver Disease.}, journal = {Seminars in liver disease}, volume = {36}, number = {1}, pages = {37-47}, pmid = {26870931}, issn = {1098-8971}, support = {K08 DK102902/DK/NIDDK NIH HHS/United States ; T32 DK007202/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; *Dietary Supplements/adverse effects ; *Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Host-Pathogen Interactions ; Humans ; Liver/*microbiology ; Liver Diseases/diagnosis/microbiology/*therapy ; Prebiotics ; Probiotics/therapeutic use ; Synbiotics ; Treatment Outcome ; }, abstract = {The gut microbiome is composed of a vast number of microbes in the gastrointestinal tract, which benefit host metabolism, aid in digestion, and contribute to normal immune function. Alterations in microbial composition can result in intestinal dysbiosis, which has been implicated in several diseases including obesity, inflammatory bowel disease, and liver diseases. Over the past several years, significant interactions between the intestinal microbiota and liver have been discovered, with possible mechanisms for the development as well as progression of liver disease and promising therapeutic targets to either prevent or halt the progression of liver disease. In this review the authors examine mechanisms of dysbiosis-induced liver disease; highlight current knowledge regarding the role of dysbiosis in nonalcoholic liver disease, alcoholic liver disease, and cirrhosis; and discuss potential therapeutic targets.}, }
@article {pmid26870928, year = {2016}, author = {Williamson, KD and Chapman, RW}, title = {New Therapeutic Strategies for Primary Sclerosing Cholangitis.}, journal = {Seminars in liver disease}, volume = {36}, number = {1}, pages = {5-14}, doi = {10.1055/s-0035-1571274}, pmid = {26870928}, issn = {1098-8971}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Bile Acids and Salts/metabolism ; Cholagogues and Choleretics/adverse effects/*therapeutic use ; Cholangitis, Sclerosing/etiology/metabolism/microbiology/*therapy ; *Endoscopy, Gastrointestinal/adverse effects ; *Fecal Microbiota Transplantation/adverse effects ; Gastrointestinal Microbiome/drug effects ; Humans ; Liver/*drug effects/metabolism/pathology ; Liver Cirrhosis, Biliary/etiology/metabolism/therapy ; *Molecular Targeted Therapy/adverse effects ; Risk Factors ; Signal Transduction/drug effects ; Treatment Outcome ; }, abstract = {Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, which in the majority of patients progresses to liver transplantation or death. To date, no medical treatment has been proven to be of benefit, although ursodeoxycholic acid is widely used. The etiopathogenesis of PSC is unclear, although it is associated with inflammatory bowel disease. Various hypotheses have been suggested, which have led to different therapeutic strategies. Recent studies have suggested that the microbiome may play a role in PSC, raising the possibility of efficacy of antibiotics and fecal microbiota transplantation. Gut-homing T cells may be important in the pathogenesis of PSC, and several agents are in development, targeting various receptors, integrins, and ligands on this pathway, including VAP-1, MAdCAM-1, α4β7, and CCR9. Nuclear receptor agonists such as obeticholic acid and fibrates hold promise, as do other therapies that alter bile acid composition such as norUDCA. Antifibrotic agents such as Loxl2 inhibitors are also being assessed. In conclusion, it is likely that an effective drug therapy for PSC will become available over the next decade.}, }
@article {pmid26870798, year = {2015}, author = {Bahr, SM and Weidemann, BJ and Castro, AN and Walsh, JW and deLeon, O and Burnett, CM and Pearson, NA and Murry, DJ and Grobe, JL and Kirby, JR}, title = {Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure.}, journal = {EBioMedicine}, volume = {2}, number = {11}, pages = {1725-1734}, pmid = {26870798}, issn = {2352-3964}, support = {HL098276/HL/NHLBI NIH HHS/United States ; U24 DK100469/DK/NIDDK NIH HHS/United States ; HL084207/HL/NHLBI NIH HHS/United States ; R00 HL098276/HL/NHLBI NIH HHS/United States ; R01AI108255/AI/NIAID NIH HHS/United States ; R01 AI108255/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antipsychotic Agents/administration &amp; dosage/*pharmacology ; Energy Metabolism/*drug effects ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects ; Metagenome ; Metagenomics/methods ; Mice ; Risperidone/administration &amp; dosage/*pharmacology ; Weight Gain/*drug effects ; Xenobiotics/pharmacology ; }, abstract = {Risperidone is a second-generation antipsychotic that causes weight gain. We hypothesized that risperidone-induced shifts in the gut microbiome are mechanistically involved in its metabolic consequences. Wild-type female C57BL/6J mice treated with risperidone (80 μg/day) exhibited significant excess weight gain, due to reduced energy expenditure, which correlated with an altered gut microbiome. Fecal transplant from risperidone-treated mice caused a 16% reduction in total resting metabolic rate in naïve recipients, attributable to suppression of non-aerobic metabolism. Risperidone inhibited growth of cultured fecal bacteria grown anaerobically more than those grown aerobically. Finally, transplant of the fecal phage fraction from risperidone-treated mice was sufficient to cause excess weight gain in naïve recipients, again through reduced energy expenditure. Collectively, these data highlight a major role for the gut microbiome in weight gain following chronic use of risperidone, and specifically implicates the modulation of non-aerobic resting metabolism in this mechanism.}, }
@article {pmid26870044, year = {2016}, author = {Mulcahy-O'Grady, H and Workentine, ML}, title = {The Challenge and Potential of Metagenomics in the Clinic.}, journal = {Frontiers in immunology}, volume = {7}, number = {}, pages = {29}, pmid = {26870044}, issn = {1664-3224}, abstract = {The bacteria, fungi, and viruses that live on and in us have a tremendous impact on our day-to-day health and are often linked to many diseases, including autoimmune disorders and infections. Diagnosing and treating these disorders relies on accurate identification and characterization of the microbial community. Current sequencing technologies allow the sequencing of the entire nucleic acid complement of a sample providing an accurate snapshot of the community members present in addition to the full genetic potential of that microbial community. There are a number of clinical applications that stand to benefit from these data sets, such as the rapid identification of pathogens present in a sample. Other applications include the identification of antibiotic-resistance genes, diagnosis and treatment of gastrointestinal disorders, and many other diseases associated with bacterial, viral, and fungal microbiomes. Metagenomics also allows the physician to probe more complex phenotypes such as microbial dysbiosis with intestinal disorders and disruptions of the skin microbiome that may be associated with skin disorders. Many of these disorders are not associated with a single pathogen but emerge as a result of complex ecological interactions within microbiota. Currently, we understand very little about these complex phenotypes, yet clearly they are important and in some cases, as with fecal microbiota transplants in Clostridium difficile infections, treating the microbiome of the patient is effective. Here, we give an overview of metagenomics and discuss a number of areas where metagenomics is applicable in the clinic, and progress being made in these areas. This includes (1) the identification of unknown pathogens, and those pathogens particularly hard to culture, (2) utilizing functional information and gene content to understand complex infections such as Clostridium difficile, and (3) predicting antimicrobial resistance of the community using genetic determinants of resistance identified from the sequencing data. All of these applications rely on sophisticated computational tools, and we also discuss the importance of skilled bioinformatic support for the implementation and use of metagenomics in the clinic.}, }
@article {pmid26860266, year = {2016}, author = {Kociolek, LK and Gerding, DN}, title = {Breakthroughs in the treatment and prevention of Clostridium difficile infection.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {13}, number = {3}, pages = {150-160}, pmid = {26860266}, issn = {1759-5053}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacterial Vaccines ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*drug therapy/etiology/*prevention &amp; control ; Gastrointestinal Microbiome/immunology ; Humans ; Immunologic Factors/therapeutic use ; }, abstract = {This Review summarizes the latest advances in the treatment and prevention of Clostridium difficile infection (CDI), which is now the most common health-care-associated infection in the USA. As traditional, standard CDI antibiotic therapies (metronidazole and vancomycin) are limited by their broad spectrum and further perturbation of the intestinal microbiota, which result in unacceptably high recurrence rates, novel therapeutic strategies for CDI are needed. Emerging CDI therapies are focused on limiting further perturbation of the intestinal microbiota and/or restoring the microbiota to its pre-morbid state, reducing colonization of the intestinal tract by toxigenic strains of C. difficile and bolstering the host immune response against C. difficile toxins. Fidaxomicin is associated with reduced CDI recurrences, and other emerging narrow-spectrum CDI antibiotic therapies might eventually demonstrate a similar benefit. Prevention of intestinal colonization of toxigenic strains of C. difficile can be achieved through restoration of the intestinal microbiota with faecal microbiota transplantation, as well as by colonizing the gut with nontoxigenic C. difficile strains. Finally, emerging immunological therapies, including monoclonal antibodies and vaccines against C. difficile toxins, might protect against CDI and subsequent CDI recurrences. The available clinical data for these emerging therapies, and their relative advantages and disadvantages, are described.}, }
@article {pmid26854221, year = {2016}, author = {Sommer, F and Ståhlman, M and Ilkayeva, O and Arnemo, JM and Kindberg, J and Josefsson, J and Newgard, CB and Fröbert, O and Bäckhed, F}, title = {The Gut Microbiota Modulates Energy Metabolism in the Hibernating Brown Bear Ursus arctos.}, journal = {Cell reports}, volume = {14}, number = {7}, pages = {1655-1661}, doi = {10.1016/j.celrep.2016.01.026}, pmid = {26854221}, issn = {2211-1247}, support = {615362/ERC_/European Research Council/International ; }, mesh = {Actinobacteria/classification/growth &amp; development ; Adaptation, Physiological ; Adiposity/*physiology ; Animals ; Bacteroidetes/classification/growth &amp; development ; Bile Acids and Salts/blood ; Blood Glucose/metabolism ; Carnitine/analogs &amp; derivatives/blood ; Cholesterol/blood ; Energy Metabolism/*physiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Firmicutes/classification/growth &amp; development ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Hibernation/*physiology ; Mice ; Principal Component Analysis ; Seasons ; Triglycerides/blood ; Ursidae/blood/*microbiology ; }, abstract = {Hibernation is an adaptation that helps many animals to conserve energy during food shortage in winter. Brown bears double their fat depots during summer and use these stored lipids during hibernation. Although bears seasonally become obese, they remain metabolically healthy. We analyzed the microbiota of free-ranging brown bears during their active phase and hibernation. Compared to the active phase, hibernation microbiota had reduced diversity, reduced levels of Firmicutes and Actinobacteria, and increased levels of Bacteroidetes. Several metabolites involved in lipid metabolism, including triglycerides, cholesterol, and bile acids, were also affected by hibernation. Transplantation of the bear microbiota from summer and winter to germ-free mice transferred some of the seasonal metabolic features and demonstrated that the summer microbiota promoted adiposity without impairing glucose tolerance, suggesting that seasonal variation in the microbiota may contribute to host energy metabolism in the hibernating brown bear.}, }
@article {pmid26850320, year = {2016}, author = {Chan, KS and Lee, WY and Yu, WL}, title = {Coexisting cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {49}, number = {6}, pages = {829-836}, doi = {10.1016/j.jmii.2015.12.007}, pmid = {26850320}, issn = {1995-9133}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Antiviral Agents/therapeutic use ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; *Coinfection ; Colitis/*therapy/*virology ; Cytomegalovirus/isolation &amp; purification ; Cytomegalovirus Infections/*therapy/virology ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation ; Female ; Ganciclovir/therapeutic use ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; }, abstract = {Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients with human immunodeficiency virus infection, organ transplantation, and malignancy receiving chemotherapy or ulcerative colitis receiving immunosuppressive agents. However, CMV colitis is increasingly recognized in immunocompetent hosts. Notably, CMV colitis coexisting with Clostridium difficile infection (CDI) in apparently healthy individuals has been published in recent years, which could result in high morbidity and mortality. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients with abdominal pain, watery, or especially bloody diarrhea, which could be refractory to standard treatment for CDI. As a characteristic of CDI, however, pseudomembranous colitis may be only caused by CMV infection. Real-time CMV-polymerase chain reaction (PCR) for blood and stool samples may be a useful and noninvasive diagnostic strategy to identify CMV infection when treatment of CDI eventually fails to show significant benefits. Quantitative CMV-PCR in mucosal biopsies may increase the diagnostic yield of traditional histopathology. CMV colitis is potentially life-threatening if severe complications occur, such as sepsis secondary to colitis, massive colorectal bleeding, toxic megacolon, and colonic perforation, so that may necessitate pre-emptive antiviral treatment for those who are positive for CMV-PCR in blood and/or stool samples while pending histological diagnosis.}, }
@article {pmid26846120, year = {2016}, author = {Tian, Z and Liu, J and Liao, M and Li, W and Zou, J and Han, X and Kuang, M and Shen, W and Li, H}, title = {Beneficial Effects of Fecal Microbiota Transplantation on Ulcerative Colitis in Mice.}, journal = {Digestive diseases and sciences}, volume = {61}, number = {8}, pages = {2262-2271}, pmid = {26846120}, issn = {1573-2568}, mesh = {Animals ; B-Lymphocytes, Regulatory/immunology/pathology ; CD4-Positive T-Lymphocytes ; Colitis, Ulcerative/chemically induced/microbiology/pathology/*therapy ; Colon/immunology/microbiology/*pathology ; Cytokines/immunology ; DNA, Bacterial/analysis ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Intestinal Mucosa/immunology/microbiology/*pathology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Spleen/immunology/pathology ; T-Lymphocytes, Regulatory/immunology/pathology ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic condition and the most common form of inflammatory bowel disease. The goal of standard treatment is mainly to induce and maintain remission with anti-inflammatory, immunosuppressive agents, and/or colectomy. Fecal microbiota transplantation (FMT) has been used successfully to treat relapsing or refractory Clostridium difficile infection. The alteration of microbiota in mouse models of UC as well as in patients suggested the possibility of treating UC with FMT.<br><br>AIMS: To study the effects of FMT on dextran sodium sulfate (DSS)-induced UC model in mice.<br><br>METHODS: Littermates of BALB/c and C57BL/6J were randomized into four groups: normal control , treatment with DSS for 7&#xa0;days (DSS&#xa0;-&#xa0;FMT), treatment with DSS followed by FMT for another 8&#xa0;days (DSS&#xa0;+&#xa0;FMT), and treatment with DSS and FMT followed by another 5&#xa0;days for recovery (remission). Body weight, survival rate, and DAI scores of mice in each group were recorded. Changes in distal colon were studied by histopathology. Alterations of spleen and lamina propria regulatory lymphocytes, major bacterial species in feces and inflammatory cytokines in colon were also studied.<br><br>RESULTS: C57BL/6J mice experienced more significant weight loss than BALB/c mice after DSS treatment, regardless of whether the two strains of mice were co-housed or not. FMT caused reversal of DAI scores in BALB/c but not in C57BL/6J mice. In BALB/c mice, FMT also reduced colon inflammation that was paralleled by decreased inflammatory cytokine levels, altered bacterial microbiota, and regulatory lymphocyte proportions.<br><br>CONCLUSIONS: FMT is effective in a mouse model of UC through its modulation on gut microbiota and the host immune system.}, }
@article {pmid26840058, year = {2016}, author = {Aso, K and Tsuruhara, A and Takagaki, K and Oki, K and Ota, M and Nose, Y and Tanemura, H and Urushihata, N and Sasanuma, J and Sano, M and Hirano, A and Aso, R and McGhee, JR and Fujihashi, K}, title = {Adipose-Derived Mesenchymal Stem Cells Restore Impaired Mucosal Immune Responses in Aged Mice.}, journal = {PloS one}, volume = {11}, number = {2}, pages = {e0148185}, pmid = {26840058}, issn = {1932-6203}, mesh = {Adipose Tissue/*immunology ; Aging/*immunology ; Allografts ; Animals ; CD4-Positive T-Lymphocytes/*immunology ; Cholera Toxin/toxicity ; Female ; *Immunity, Mucosal ; Immunoglobulin A, Secretory/immunology ; Interferon-gamma/immunology ; Interleukin-4/immunology ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*immunology ; Mice ; Peyer's Patches/*immunology ; }, abstract = {It has been shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into adipocytes, chondrocytes and osteoblasts. Several clinical trials have shown the ability of AMSCs to regenerate these differentiated cell types. Age-associated dysregulation of the gastrointestinal (GI) immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier during agingthan is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice. Aged (>18 mo old) mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA) plus cholera toxin (CT) three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA- and CT-B-specific ELISA, elevated levels of mucosal secretory IgA (SIgA) and plasma IgG antibody (Ab) responses were noted in aged mouse recipients. Similar results were also seen aged mice which received AMSCs at one year of age. When cytokine production was examined, OVA-stimulated Peyer's patch CD4+ T cells produced increased levels of IL-4. Further, CD4+ T cells from the lamina propria revealed elevated levels of IL-4 and IFN-γ production. In contrast, aged mice without AMSC transfer showed essentially no OVA- or CT-B-specific mucosal SIgA or plasma IgG Ab or cytokine responses. Of importance, fecal extracts from AMSC transferred aged mice showed neutralization activity to CT intoxication. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice.}, }
@article {pmid26832403, year = {2016}, author = {Lichtman, JS and Ferreyra, JA and Ng, KM and Smits, SA and Sonnenburg, JL and Elias, JE}, title = {Host-Microbiota Interactions in the Pathogenesis of Antibiotic-Associated Diseases.}, journal = {Cell reports}, volume = {14}, number = {5}, pages = {1049-1061}, pmid = {26832403}, issn = {2211-1247}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; R01-DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; *Disease ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Host-Pathogen Interactions ; Inflammation/pathology ; Male ; Mice ; *Microbiota ; Proteome ; }, abstract = {Improved understanding of the interplay between host and microbes stands to illuminate new avenues for disease diagnosis, treatment, and prevention. Here, we provide a high-resolution view of the dynamics between host and gut microbiota during antibiotic-induced intestinal microbiota depletion, opportunistic Salmonella typhimurium and Clostridium difficile pathogenesis, and recovery from these perturbed states in a mouse model. Host-centric proteome and microbial community profiles provide a nuanced longitudinal view, revealing the interdependence between host and microbiota in evolving dysbioses. Time- and condition-specific molecular and microbial signatures are evident and clearly distinguished from pathogen-independent inflammatory fingerprints. Our data reveal that mice recovering from antibiotic treatment or C. difficile infection retain lingering signatures of inflammation, despite compositional normalization of the microbiota, and host responses could be rapidly and durably relieved through fecal transplant. These experiments demonstrate insights that emerge from the combination of these orthogonal, untargeted approaches to the gastrointestinal ecosystem.}, }
@article {pmid26827672, year = {2016}, author = {Kicia, M and Wesolowska, M and Kopacz, Z and Jakuszko, K and Sak, B and Květonová, D and Krajewska, M and Kváč, M}, title = {Prevalence and molecular characteristics of urinary and intestinal microsporidia infections in renal transplant recipients.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {22}, number = {5}, pages = {462.e5-9}, doi = {10.1016/j.cmi.2016.01.014}, pmid = {26827672}, issn = {1469-0691}, mesh = {Adolescent ; Adult ; Aged ; Diarrhea/epidemiology/microbiology ; Feces/microbiology ; Female ; Genotyping Techniques ; Humans ; *Kidney Transplantation ; Male ; Microsporidia/*classification/*genetics/isolation &amp; purification ; Microsporidiosis/*epidemiology/*microbiology ; Middle Aged ; Prevalence ; *Transplant Recipients ; Urinary Tract Infections/epidemiology/microbiology ; Urine/microbiology ; Young Adult ; }, abstract = {Transplant recipients have been identified as a new risk group for microsporidia infection. We characterize for the first time the prevalence of microsporidia in intestinal and urinary tracts of renal transplant recipients. Molecular examination of 86 patients showed that 25.5% of them were infected; 86% were confirmed to have pathogens in their urine and 45.5% in stool. Among positive patients, 32% had microsporidia confirmed in both urine and stool. Genotyping revealed Encephalitozoon cuniculi (59%) and Enterocytozoon bieneusi (23%) monoinfections as well as coinfections with both species (18%). Moreover, we found diarrhoea and fever as symptoms significantly associated with microsporidia presence. Our results indicate that microsporidial infection should be considered in the assessment of renal transplant recipients, especially in the urinary tract, even if asymptomatic. Molecular identification of microsporidia species is relevant because of their different susceptibility for treatment.}, }
@article {pmid26826616, year = {2016}, author = {Didesch, MM and Averill, A and Oh-Park, M}, title = {Peripheral Neuropathy After Fecal Microbiota Transplantation for Clostridium difficile Infection: A Case Report.}, journal = {PM &amp; R : the journal of injury, function, and rehabilitation}, volume = {8}, number = {8}, pages = {813-816}, doi = {10.1016/j.pmrj.2016.01.009}, pmid = {26826616}, issn = {1934-1563}, mesh = {Aged ; Clostridioides difficile ; Clostridium Infections ; Fecal Microbiota Transplantation ; Feces ; Humans ; Male ; *Peripheral Nervous System Diseases ; }, abstract = {We present a case of a 71-year-old man with Clostridium difficile infection who underwent fecal transplantation. The patient was found to have a predominantly demyelinating sensorimotor peripheral polyneuropathy upon electrodiagnostic testing. To our knowledge, only one case of peripheral neuropathy after fecal transplantation has previously been reported. Although the exact cause of this patient's neuropathy cannot be confirmed, it has been speculated that the pathophysiology is an immune-mediated process. Given the increasing incidence of C difficile infections and the emergence of fecal transplantation as treatment, it is important to note that peripheral neuropathy is a potential adverse complication.}, }
@article {pmid26825565, year = {2016}, author = {Samuel, BP and Crumb, TL and LaVigne, HD}, title = {NURSING ASSESSMENT FOR "DO IT YOURSELF" FECAL MICROBIOTA TRANSPLANTATION.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {39}, number = {1}, pages = {60-62}, doi = {10.1097/SGA.0000000000000142}, pmid = {26825565}, issn = {1538-9766}, mesh = {Child, Preschool ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/nursing/*therapy ; *Fecal Microbiota Transplantation/methods ; Humans ; Male ; Nursing Assessment ; }, }
@article {pmid26821578, year = {2016}, author = {Gathe, JC and Diejomaoh, EM and Mayberry, CC and Clemmons, JB}, title = {Fecal Transplantation for Clostridium Difficile-"All Stool May Not Be Created Equal".}, journal = {Journal of the International Association of Providers of AIDS Care}, volume = {15}, number = {2}, pages = {107-108}, doi = {10.1177/2325957415627695}, pmid = {26821578}, issn = {2325-9574}, mesh = {Clostridioides difficile/*physiology ; Diarrhea/therapy ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Humans ; Middle Aged ; Treatment Outcome ; }, abstract = {Clostridium difficile is a gram-positive bacterium that is recognized as a causative organism of pseudomembranous enterocolitis. This infection has become a major public health challenge and is a source of considerable morbidity and mortality in those infected. We present a 62-year-old African American female with a long history of HIV infection, who presented with abdominal pain and continuous diarrhea due to pseudomembranous colitis. After failing multiple episodes of conventional therapy, it was decided to treat her with fecal microbiota transplantation. Fecal microbiota transplantation was given on 3 separate occasions from a biological-related donor without success. It was only after a fourth transplant was done with a nonrelated donor that the patient resolved her diarrhea within 48 hours. We suggest that fecal samples from different donors have different abilities to cure Clostridium difficile colitis in at least this immunosuppressed patient.}, }
@article {pmid26817477, year = {2015}, author = {Singh, B and Qin, N and Reid, G}, title = {Microbiome Regulation of Autoimmune, Gut and Liver Associated Diseases.}, journal = {Inflammation &amp; allergy drug targets}, volume = {14}, number = {2}, pages = {84-93}, doi = {10.2174/1871528114666160128150747}, pmid = {26817477}, issn = {2212-4055}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Autoimmune Diseases/epidemiology/immunology/*microbiology/therapy ; Bacteria/drug effects/genetics/*growth &amp; development/immunology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Diseases/epidemiology/immunology/*microbiology/therapy ; *Gastrointestinal Microbiome/drug effects ; Gastrointestinal Tract/drug effects/immunology/*microbiology ; Human Migration ; Humans ; Liver Diseases/epidemiology/immunology/*microbiology/therapy ; Protective Factors ; Risk Factors ; }, abstract = {Extensive analysis of the complexity and diversity of microbiota using metagenomics in the gut and other body sites has provided evidence that dysbiosis occurs in many disease states. With the application of next generation sequencing technology this research is starting to uncover the impact of microbiota on metabolic, physiological and immunological pathways and elucidate the cellular and molecular mechanisms involved. To highlight these advances we have focused on autoimmunity and gut and liver related diseases and discuss the opportunities and challenges of translating microbiome research towards its application in humans. Towards this goal we discuss the application of fecal microbiome transplantation (FMT) for the treatment of multiple chronic gut associated inflammatory diseases such as Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). The potential role of human migration across continents and cultures leading to alteration in their microbiome and its implication in health and disease is also discussed.}, }
@article {pmid26815640, year = {2016}, author = {Boudjellil, R and Elbaz, M and Lairez, O and Lhomme, S and Izopet, J and Kamar, N}, title = {No evidence of genotype-3 hepatitis E virus-induced myocarditis.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {76}, number = {}, pages = {44}, doi = {10.1016/j.jcv.2016.01.011}, pmid = {26815640}, issn = {1873-5967}, mesh = {Adolescent ; Adult ; Feces/virology ; Female ; Genotype ; Hepatitis E virus/genetics/*isolation &amp; purification ; Humans ; Male ; Myocarditis/diagnosis/etiology/*virology ; RNA, Viral/analysis/blood ; Young Adult ; }, }
@article {pmid26810816, year = {2016}, author = {Patel, K and Spector, TD}, title = {Estimating the risks of faecal transplants.}, journal = {The Journal of hospital infection}, volume = {92}, number = {2}, pages = {128-129}, doi = {10.1016/j.jhin.2015.11.017}, pmid = {26810816}, issn = {1532-2939}, mesh = {*Fecal Microbiota Transplantation ; *Feces ; Humans ; }, }
@article {pmid26803556, year = {2016}, author = {Baxter, M and Colville, A}, title = {Adverse events in faecal microbiota transplant: a review of the literature.}, journal = {The Journal of hospital infection}, volume = {92}, number = {2}, pages = {117-127}, doi = {10.1016/j.jhin.2015.10.024}, pmid = {26803556}, issn = {1532-2939}, mesh = {Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/prevention &amp; control ; Diarrhea/microbiology/prevention &amp; control ; Fecal Microbiota Transplantation/*adverse effects/methods ; Humans ; Recurrence ; Secondary Prevention/methods ; }, abstract = {BACKGROUND: Faecal microbiota transplant (FMT) is the infusion of donor faeces into the gut with the aim of improving microbial diversity. The procedure has gained significant interest recently in the treatment of recurrent Clostridium difficile infection (CDI). The literature is currently dominated by small case series and isolated case reports. There is no standardization of methods and recording of outcomes.<br><br>AIM: To present the adverse events that have been associated with the use of FMT, as reported in the English literature to date.<br><br>METHODS: A database search of Medline and Embase identified publications where FMT has been administered. Review articles were excluded. In total, 109 publications were identified that described the use of FMT in 1555 individuals.<br><br>FINDINGS: Other than three small randomized controlled studies, the data consisted of small series and case reports. CDI was the most common indication for FMT (N&#xa0;=&#xa0;1190), with the majority of the remaining cases receiving FMT for inflammatory bowel disease. FMT had also been applied for irritable bowel syndrome, metabolic syndrome and constipation in small numbers. Adverse events appear to be uncommon, often mild and self-limiting; however, serious adverse events including bacteraemia, perforations and death have been reported.<br><br>CONCLUSION: The vast majority of adverse events of FMT appear to be mild, self-limiting and gastrointestinal in nature. In some cases, a credible association was not established due to the lack of controlled data. There is a need for standardized, randomized controlled trials to qualify and quantify the risks associated with FMT.}, }
@article {pmid26799197, year = {2016}, author = {Yan, K and Garcia-Tsao, G}, title = {Novel prevention strategies for bacterial infections in cirrhosis.}, journal = {Expert opinion on pharmacotherapy}, volume = {17}, number = {5}, pages = {689-701}, pmid = {26799197}, issn = {1744-7666}, support = {P30 DK34989/DK/NIDDK NIH HHS/United States ; U01 AA021908/AA/NIAAA NIH HHS/United States ; T35 DK104689/DK/NIDDK NIH HHS/United States ; T35DK104689/DK/NIDDK NIH HHS/United States ; P30 DK034989/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Bacterial Infections/complications/*prevention &amp; control ; Bacterial Translocation ; Gastrointestinal Agents/therapeutic use ; Gastrointestinal Motility ; Humans ; Intestines/microbiology/physiopathology ; Liver Cirrhosis/*complications ; Probiotics/*therapeutic use ; Rifamycins/therapeutic use ; Rifaximin ; }, abstract = {INTRODUCTION: Bacterial infections are a serious complication of cirrhosis, as they can lead to decompensation, multiple organ failure, and/or death. Preventing infections is therefore very relevant. Because gut bacterial translocation is their main pathogenic mechanism, prevention of infections is mostly based on the use of orally administered poorly absorbed antibiotics such as norfloxacin (selective intestinal decontamination). However, antibiotic prophylaxis leads to antibiotic resistance, limiting therapy and increasing morbidity and mortality. Prevention of bacterial infections in cirrhosis should therefore move away from antibiotics.<br><br>AREAS COVERED: This review focuses on various potentially novel methods to prevent infections in cirrhosis focusing on non-antibiotic strategies. The use of probiotics, nonselective intestinal decontamination with rifaximin, prokinetics and beta-blockers or fecal microbiota transplant as means of targeting altered gut microbiota, bile acids and FXR agonists are all potential alternatives to selective intestinal decontamination. Prokinetics and beta-blockers can improve intestinal motility, while bile acids and FXR agonists help by improving the intestinal barrier. Finally, granulocyte colony stimulating factor (G-CSF) and statins are emerging therapeutic strategies that may improve immune dysfunction in cirrhosis.<br><br>EXPERT OPINION: Evidence for these strategies has been restricted to animal studies and proof-of concept studies but we expect this to change in coming years.}, }
@article {pmid26796081, year = {2016}, author = {Garey, KW and Aitken, SL and Gschwind, L and Goddu, S and Xie, Y and Duff, C and Barbut, F and Shah, DN and DuPont, HL}, title = {Development and Validation of a Clostridium difficile Health-related Quality-of-Life Questionnaire.}, journal = {Journal of clinical gastroenterology}, volume = {50}, number = {8}, pages = {631-637}, pmid = {26796081}, issn = {1539-2031}, mesh = {Adult ; Aged ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*physiopathology ; Factor Analysis, Statistical ; Female ; Health Surveys ; Humans ; Male ; Middle Aged ; Psychometrics ; *Quality of Life ; Recurrence ; *Surveys and Questionnaires ; }, abstract = {GOALS AND BACKGROUND: Patients with Clostridium difficile infection (CDI) can experience long-term symptoms and poor quality of life due to the disease. Despite this, a health-related quality of life (HRQOL) instrument specific for patients with CDI does not exist. The aim of this study was to develop and validate a disease-specific instrument to assess HRQOL in patients with CDI.<br><br>STUDY: A systematic literature review was conducted to identify HRQOL instruments and questions related to general health (n=3) or gastrointestinal disease (n=12) potentially related to CDI HRQOL. Removing duplicate questions and using direct patient or clinician interviews, a 36-item survey was developed. The survey was then tested using 98 patients with CDI and compared with the RAND Short-Form 36 (SF-36) Health Survey. Psychometric analysis techniques were used to identify domains and remove redundant items.<br><br>RESULTS: Exploratory factor analysis identified 3 major domains (physical, mental, and social) with 4 associated subdomains. Survey overall and domain scores displayed good internal consistency (Cronbach &#x3b1; coefficient >0.87) and concurrent validity evidenced by significant correlation with SF-36 scores. The C. difficile survey scores were better able than the SF-36 to discriminate quality-of-life score differences in patients with primary versus recurrent CDI and increasing time since last episode of CDI. The final version contained 32 items related to the physical, mental, and social health of CDI patients.<br><br>CONCLUSION: The properties of the newly developed Cdiff32 should make it appropriate to assess changes over time in HRQOL in patients with CDI.}, }
@article {pmid26792682, year = {2016}, author = {Goldenberg, SD}, title = {Faecal microbiota transplantation for recurrent Clostridium difficile infection and beyond: risks and regulation.}, journal = {The Journal of hospital infection}, volume = {92}, number = {2}, pages = {115-116}, doi = {10.1016/j.jhin.2015.12.004}, pmid = {26792682}, issn = {1532-2939}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*prevention &amp; control ; Diarrhea/microbiology/*prevention &amp; control ; Fecal Microbiota Transplantation/*adverse effects/*methods ; Humans ; Recurrence ; Risk ; Secondary Prevention/*methods ; Social Control, Formal ; }, }
@article {pmid26789728, year = {2016}, author = {Weingarden, AR and Dosa, PI and DeWinter, E and Steer, CJ and Shaughnessy, MK and Johnson, JR and Khoruts, A and Sadowsky, MJ}, title = {Changes in Colonic Bile Acid Composition following Fecal Microbiota Transplantation Are Sufficient to Control Clostridium difficile Germination and Growth.}, journal = {PloS one}, volume = {11}, number = {1}, pages = {e0147210}, pmid = {26789728}, issn = {1932-6203}, support = {R21 AI114722/AI/NIAID NIH HHS/United States ; R21 AI091907/AI/NIAID NIH HHS/United States ; UL1TR00114/TR/NCATS NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; 2T32AI055433-06A1/AI/NIAID NIH HHS/United States ; 1R21-AI114722-01/AI/NIAID NIH HHS/United States ; T32 AI055433/AI/NIAID NIH HHS/United States ; R21AI-091907/AI/NIAID NIH HHS/United States ; }, mesh = {Bile Acids and Salts/*metabolism ; Biological Therapy/*methods ; Clostridioides difficile/*growth &amp; development/isolation &amp; purification/pathogenicity ; Colon/*metabolism/microbiology ; Enterocolitis, Pseudomembranous/microbiology/*prevention &amp; control ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; }, abstract = {Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI), but its mechanisms remain poorly understood. Emerging evidence suggests that gut bile acids have significant influence on the physiology of C. difficile, and therefore on patient susceptibility to recurrent infection. We analyzed spore germination of 10 clinical C. difficile isolates exposed to combinations of bile acids present in patient feces before and after FMT. Bile acids at concentrations found in patients' feces prior to FMT induced germination of C. difficile, although with variable potency across different strains. However, bile acids at concentrations found in patients after FMT did not induce germination and inhibited vegetative growth of all C. difficile strains. Sequencing of the newly identified germinant receptor in C. difficile, CspC, revealed a possible correspondence of variation in germination responses across isolates with mutations in this receptor. This may be related to interstrain variability in spore germination and vegetative growth in response to bile acids seen in this and other studies. These results support the idea that intra-colonic bile acids play a key mechanistic role in the success of FMT, and suggests that novel therapeutic alternatives for treatment of R-CDI may be developed by targeted manipulation of bile acid composition in the colon.}, }
@article {pmid26787597, year = {2016}, author = {Aigner, F and Kronberger, I and Oberwalder, M and Loizides, A and Ulmer, H and Gruber, L and Pratschke, J and Peer, S and Gruber, H}, title = {Doppler-guided haemorrhoidal artery ligation with suture mucopexy compared with suture mucopexy alone for the treatment of Grade III haemorrhoids: a prospective randomized controlled trial.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {18}, number = {7}, pages = {710-716}, doi = {10.1111/codi.13280}, pmid = {26787597}, issn = {1463-1318}, mesh = {Adult ; Arteries/*surgery ; Female ; Hemorrhoids/*surgery ; Humans ; Ligation/methods ; Male ; Middle Aged ; Postoperative Complications/etiology ; Prospective Studies ; Rectal Prolapse/*surgery ; *Suture Techniques ; Treatment Outcome ; Ultrasonography, Doppler ; Ultrasonography, Interventional/*methods ; }, abstract = {AIM: Novel minimally invasive techniques aimed to reposition the haemorrhoidal zone have been established for prolapsing haemorrhoids. We present a prospective randomized controlled trial to evaluate the efficacy of additional Doppler-guided ligation of submucosal haemorrhoidal arteries (DG-HAL) in patients with symptomatic Grade III haemorrhoids. The trial was registered as ClinicalTrials.gov identifier NCT02372981.<br><br>METHOD: All consecutive patients with symptomatic Grade III haemorrhoids were randomly allocated to one of the two study arms: (i) Group A, DG-HAL with mucopexy or (ii) Group B, mucopexy alone. End-points were postoperative pain, faecal incontinence, bleeding, residual prolapse and alterations of the vascularization of the anorectal vascular plexus. Vascularization of the anorectal vascular plexus was assessed by transperineal contrast enhanced ultrasound. Patients recorded their symptoms in a diary maintained for a month.<br><br>RESULTS: Forty patients were recruited and randomized to the two study groups. Patients in Group A had less pain in the first two postoperative weeks. At the 12-month follow-up, two patients in Group A (10%) and one in Group B (5%) showed recurrent Grade III haemorrhoids (P&#xa0;=&#xa0;0.274). No significant morphological changes were observed in the transperineal ultrasound findings between the preoperative assessment and the assessment at 1 and 6&#xa0;months in either group (P&#xa0;>&#xa0;0.05).<br><br>CONCLUSION: Mucopexy techniques for treating prolapsing haemorrhoids are effective, but DG-HAL does not add significantly to the results achieved by mucopexy. Repositioning the haemorrhoidal zone is the key to success, and mucopexy should be placed at the sites of the largest visible prolapse.}, }
@article {pmid26781928, year = {2015}, author = {Osseis, M and Lim, C and Lahat, E and Doussot, A and Salloum, C and Azoulay, D}, title = {Hepatic venous outflow block caused by compressive fecaloma in a schizophrenic patient treated with clozapine.}, journal = {Drug discoveries &amp; therapeutics}, volume = {9}, number = {6}, pages = {422-423}, doi = {10.5582/ddt.2015.01067}, pmid = {26781928}, issn = {1881-7831}, mesh = {Antipsychotic Agents/*adverse effects ; Budd-Chiari Syndrome/*etiology ; Clozapine/*adverse effects ; Fecal Impaction/*complications ; Humans ; Male ; Middle Aged ; Schizophrenia/*drug therapy ; }, abstract = {In Clozapine users constipation is among the reported side effects including agranulocytosis and myocarditis with prevalence rates ranging from 14% to 60%. In extreme cases this may lead to bowel obstruction and paralytic ileus which, if not detected and treated early, may lead to mortality up to 30%. We report the first case of hepatic outflow block secondary to compression of the liver by a distended colon upstream an impacted fecaloma in a 47-year old schizophrenic man treated by clozapine. Emergency sub-total colectomy was performed for pan-colonic ischemia. Surgery relieved the liver outflow block and was followed by uneventful outcome. Patients receiving clozapine should undergo routine laxatives and monitoring in order to limit the risk of clozapine-related ileus and bowel ischemia.}, }
@article {pmid26775532, year = {2015}, author = {Leis, S and Borody, TJ and Jiang, C and Campbell, J}, title = {Fecal microbiota transplantation: A 'How-To' guide for nurses.}, journal = {Collegian (Royal College of Nursing, Australia)}, volume = {22}, number = {4}, pages = {445-451}, pmid = {26775532}, issn = {1322-7696}, mesh = {Colonoscopy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Microbiota ; Nursing Staff ; *Practice Guidelines as Topic ; }, abstract = {Fecal microbiota transplantation is emerging as one of the most exciting treatments of this century. Rarely has one treatment provided the opportunity to treat a myriad of diseases, not only within the gastrointestinal tract but also in extra-intestinal organs; such is the power of the gastrointestinal microbiota to modulate the immune system and eradicate infections, even where antibiotics have previously failed. The demand for this therapy, both among patients and physicians, is increasing, and a search of the literature reveals numerous reviews, case reports and discussion on the topic. However, to date, much of the literature addresses the procedure from a physician's point of view, and can therefore be lacking in practical detail. As nurses are often the 'unsung heroes' of the procedure, it is timely to address the subject from a nursing perspective.}, }
@article {pmid26771898, year = {2016}, author = {Waltz, P and Zuckerbraun, B}, title = {Novel therapies for severe Clostridium difficile colitis.}, journal = {Current opinion in critical care}, volume = {22}, number = {2}, pages = {167-173}, doi = {10.1097/MCC.0000000000000282}, pmid = {26771898}, issn = {1531-7072}, mesh = {Anti-Infective Agents/*therapeutic use ; Clostridioides difficile/*drug effects ; Clostridium Infections/microbiology/*therapy ; Colitis/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods/trends ; Fluid Therapy/*methods/trends ; Humans ; Practice Guidelines as Topic ; Recurrence ; Risk Factors ; }, abstract = {PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is becoming a large healthcare burden with increasing incidence, high recurrence rates, and associated morbidity and mortality. Disease severity varies from mild to severe and complicated presentations. Current mainstays of therapy in severe CDI include: fluid resuscitation, support of organ dysfunction, discontinuation of inciting agents, and antibiotic treatment.<br><br>RECENT FINDINGS: Recent focus on the impact of the microbiome and targeted therapies to reconstitute biodiversity may provide alternative therapeutic modalities with higher success and lower recurrence rates. Newer antibiotics are under development, along with targeted immunotherapies that attempt to neutralize pathogenic toxins. Alternative surgical options from traditional subtotal colectomy may provide a less morbid surgical option for those requiring intervention.<br><br>SUMMARY: With further understanding of the pathogenesis and shortcomings of current therapies, the future of management of CDI may include a multimodal approach focusing on microbiota and immunologic therapies that could result in improved cure with reduced recurrence.}, }
@article {pmid26770128, year = {2015}, author = {Bull, MJ and Plummer, NT}, title = {Part 2: Treatments for Chronic Gastrointestinal Disease and Gut Dysbiosis.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {14}, number = {1}, pages = {25-33}, pmid = {26770128}, issn = {1546-993X}, abstract = {Part 1 of this review discussed the connection between the human gut microbiota and health. Manipulation of the intestinal microbiota holds promise as a prospective therapy for gut dysbiosis, ameliorating symptoms of gastrointestinal and systemic diseases and restoring health. The concept of probiotics has existed for more than 100 y, and modern research methods have established sound scientific support for the perceived benefits of probiotic bacteria, which mainly include Lactobacillus and Bifidobacterium genera. On the basis of these evidence-based functional approaches, dietary interventions that supplement the normal diet with probiotics or prebiotics are now considered as potentially viable alternatives or adjuncts to the use of steroids, immunosuppressants, and/or surgical interventions. Studies investigating the impact on gastrointestinal disorders, such as diarrhea, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS); and systemic metabolic diseases, such as type 2 diabetes and obesity, in response to the use of probiotics and prebiotics are reviewed. Further, fecal microbial transplantation (FMT) is discussed as an exciting development in the treatment of gut dysbiosis using microbes.}, }
@article {pmid26764595, year = {2016}, author = {Liu, S and da Cunha, AP and Rezende, RM and Cialic, R and Wei, Z and Bry, L and Comstock, LE and Gandhi, R and Weiner, HL}, title = {The Host Shapes the Gut Microbiota via Fecal MicroRNA.}, journal = {Cell host &amp; microbe}, volume = {19}, number = {1}, pages = {32-43}, pmid = {26764595}, issn = {1934-6069}, support = {P30 DK034854/DK/NIDDK NIH HHS/United States ; R01 AI043458/AI/NIAID NIH HHS/United States ; R01 NS087226/NS/NINDS NIH HHS/United States ; R01 AI43458/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Feces/chemistry/*microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism/*microbiology ; Humans ; Mice ; MicroRNAs/genetics/*metabolism ; }, abstract = {The host gut microbiota varies across species and individuals but is relatively stable over time within an individual. How the host selectively shapes the microbiota is largely unclear. Here, we show that fecal microRNA (miRNA)-mediated inter-species gene regulation facilitates host control of the gut microbiota. miRNAs are abundant in mouse and human fecal samples and present within extracellular vesicles. Cell-specific loss of the miRNA-processing enzyme, Dicer, identified intestinal epithelial cells (IEC) and Hopx-positive cells as predominant fecal miRNA sources. These miRNAs can enter bacteria, such as F. nucleatum and E. coli, specifically regulate bacterial gene transcripts, and affect bacterial growth. IEC-miRNA-deficient (Dicer1(ΔIEC)) mice exhibit uncontrolled gut microbiota and exacerbated colitis, and WT fecal miRNA transplantation restores fecal microbes and ameliorates colitis. These findings identify both a physiologic role by which fecal miRNA shapes the gut microbiota and a potential strategy for manipulating the microbiome.}, }
@article {pmid26763967, year = {2016}, author = {Feghoul, L and Salmona, M and Cherot, J and Fahd, M and Dalle, JH and Vachon, C and Perrod, A and Bourgeois, P and Scieux, C and Baruchel, A and Simon, F and LeGoff, J}, title = {Evaluation of a New Device for Simplifying and Standardizing Stool Sample Preparation for Viral Molecular Testing with Limited Hands-On Time.}, journal = {Journal of clinical microbiology}, volume = {54}, number = {4}, pages = {928-933}, pmid = {26763967}, issn = {1098-660X}, mesh = {Adenoviridae Infections/*diagnosis/virology ; Child, Preschool ; Feces/*virology ; Gastroenteritis/*diagnosis/virology ; Humans ; Infant ; Infant, Newborn ; Molecular Diagnostic Techniques/*methods/standards ; Reproducibility of Results ; Sensitivity and Specificity ; Specimen Handling/*methods/standards ; Viral Load/methods ; }, abstract = {Sensitive molecular assays have greatly improved the diagnosis of viral gastroenteritis. However, the proper preparation of stool samples for clinical testing remains an issue. bioMérieux has developed a stool preprocessing device (SPD) that includes a spoon for calibrated sampling and a vial containing buffer, glass beads, and two filters. The resulting stool filtrate is used for nucleic acid extraction. The purpose of this study was to evaluate the performance of the SPD for the quantification of human adenovirus (HAdV) DNA in stool samples collected from hematopoietic stem cell transplant (HSCT) recipients. HAdV DNA was quantified with the Adenovirus R-gene kit. The suitability of the device to reproducibly quantify HAdV DNA in stools using different extraction platforms (easyMAG and QIAsymphony) was determined using archived HAdV-positive stool samples. Coefficients of variation of HAdV DNA quantifications ranged from 1.79% to 1.83%, and no difference in quantification was observed between the two extraction systems. The HAdV DNA limit of quantification using the SPD was 3.75 log10copies/g of stool. HAdV DNA quantification using the SPD was then compared to that of the routine preprocessing technique on 75 fresh stool samples collected prospectively from pediatric HSCT recipients at risk for HAdV infections. Thirty-eight samples were HAdV DNA positive with both the SPD and routine preprocessing methods. HAdV DNA loads were on average 1.14-log10copies/g of stool higher with the SPD (P< 0.0001) than with routine methods. This new device enabled a standardized preparation of stool samples in <5 min and a reproducible and sensitive quantification of HAdV DNA. The use of the SPD for the detection of other gastrointestinal infections warrants further evaluation.}, }
@article {pmid26762459, year = {2016}, author = {Sonnenburg, ED and Smits, SA and Tikhonov, M and Higginbottom, SK and Wingreen, NS and Sonnenburg, JL}, title = {Diet-induced extinctions in the gut microbiota compound over generations.}, journal = {Nature}, volume = {529}, number = {7585}, pages = {212-215}, pmid = {26762459}, issn = {1476-4687}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; R01-DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Animals ; Bacteroidetes/drug effects ; Diet/*adverse effects ; Dietary Carbohydrates/administration &amp; dosage ; Dietary Fiber/administration &amp; dosage ; *Extinction, Biological ; Fecal Microbiota Transplantation ; Female ; Fermentation/drug effects ; *Gastrointestinal Microbiome/drug effects ; Gastrointestinal Tract/drug effects/microbiology ; Germ-Free Life ; Healthy Volunteers ; Humans ; Male ; Mice ; Pedigree ; }, abstract = {The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including immune function and metabolism. The reduced diversity of the gut microbiota in Western populations compared to that in populations living traditional lifestyles presents the question of which factors have driven microbiota change during modernization. Microbiota-accessible carbohydrates (MACs) found in dietary fibre have a crucial involvement in shaping this microbial ecosystem, and are notably reduced in the Western diet (high in fat and simple carbohydrates, low in fibre) compared with a more traditional diet. Here we show that changes in the microbiota of mice consuming a low-MAC diet and harbouring a human microbiota are largely reversible within a single generation. However, over several generations, a low-MAC diet results in a progressive loss of diversity, which is not recoverable after the reintroduction of dietary MACs. To restore the microbiota to its original state requires the administration of missing taxa in combination with dietary MAC consumption. Our data illustrate that taxa driven to low abundance when dietary MACs are scarce are inefficiently transferred to the next generation, and are at increased risk of becoming extinct within an isolated population. As more diseases are linked to the Western microbiota and the microbiota is targeted therapeutically, microbiota reprogramming may need to involve strategies that incorporate dietary MACs as well as taxa not currently present in the Western gut.}, }
@article {pmid26762142, year = {2016}, author = {Wise, J}, title = {Frozen faecal matter works as well as fresh for transplantation in C difficile patients.}, journal = {BMJ (Clinical research ed.)}, volume = {352}, number = {}, pages = {i138}, doi = {10.1136/bmj.i138}, pmid = {26762142}, issn = {1756-1833}, mesh = {*Clostridioides difficile ; *Cryopreservation ; Diarrhea/*therapy ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; }, }
@article {pmid26758971, year = {2016}, author = {Souza, &#xc9;L and Elian, SD and Paula, LM and Garcia, CC and Vieira, AT and Teixeira, MM and Arantes, RM and Nicoli, JR and Martins, FS}, title = {Escherichia coli strain Nissle 1917 ameliorates experimental colitis by modulating intestinal permeability, the inflammatory response and clinical signs in a faecal transplantation model.}, journal = {Journal of medical microbiology}, volume = {65}, number = {3}, pages = {201-210}, doi = {10.1099/jmm.0.000222}, pmid = {26758971}, issn = {1473-5644}, mesh = {Animals ; Colitis/*chemically induced ; Dextran Sulfate/toxicity ; Escherichia coli/*classification/*physiology ; Feces ; Female ; Germ-Free Life ; Inflammation/metabolism ; Intestines/microbiology/pathology/*physiology ; Mice ; Mice, Inbred BALB C ; Permeability ; *Probiotics ; }, abstract = {Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions of the gut that include ulcerative colitis and Crohn's disease. Probiotics are live micro-organisms that may be used as adjuvant therapy for patients with IBD. The aim of this study was to evaluate the effect of prophylactic ingestion of Escherichia coli strain Nissle 1917 (EcN) in a murine model of colitis. For induction of colitis, mice were given a 3.5% dextran sodium sulfate (DSS) solution for 7 days in drinking water. EcN administration to mice subjected to DSS-induced colitis resulted in significant reduction in clinical and histopathological signs of disease and preservation of intestinal permeability. We observed reduced inflammation, as assessed by reduced levels of neutrophils, eosinophils, chemokines and cytokines. We observed an increase in the number of regulatory T-cells in Peyer's patches. Germ-free mice received faecal content from control or EcN-treated mice and were then subjected to DSS-induced colitis. We observed protection from colitis in animals that were colonized with faecal content from EcN-treated mice. These results suggest that preventative oral administration of EcN or faecal microbiota transplantation with EcN-containing microbiota ameliorates DSS-induced colitis by modifying inflammatory responsiveness to DSS.}, }
@article {pmid26758906, year = {2016}, author = {Kumar, R and Maynard, CL and Eipers, P and Goldsmith, KT and Ptacek, T and Grubbs, JA and Dixon, P and Howard, D and Crossman, DK and Crowley, MR and Benjamin, WH and Lefkowitz, EJ and Weaver, CT and Rodriguez, JM and Morrow, CD}, title = {Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile.}, journal = {BMC microbiology}, volume = {16}, number = {}, pages = {5}, pmid = {26758906}, issn = {1471-2180}, support = {P30 AI027767/AI/NIAID NIH HHS/United States ; UL1TR000165/TR/NCATS NIH HHS/United States ; T32 AI007051/AI/NIAID NIH HHS/United States ; UL1 TR000165/TR/NCATS NIH HHS/United States ; P30 CA013148/CA/NCI NIH HHS/United States ; 5P30AI027767/AI/NIAID NIH HHS/United States ; P30 AR050948/AR/NIAMS NIH HHS/United States ; UL1 TR001417/TR/NCATS NIH HHS/United States ; P30AR050948/AR/NIAMS NIH HHS/United States ; T32 AI052069/AI/NIAID NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Animals ; Bacteria/classification/genetics/*growth &amp; development/isolation &amp; purification ; Clostridioides difficile/*physiology ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Fecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient's gut commensal microbiota, we have analyzed the colonization potential of the donor, recipient and recipient post transplant fecal samples using transplantation in gnotobiotic mice.<br><br>RESULTS: A total of nine samples from three human donors, recipient's pre and post FMT were transplanted into gnotobiotic mice. Microbiome analysis of three donor fecal samples revealed the presence of a high relative abundance of commensal microbes from the family Bacteriodaceae and Lachnospiraceae that were almost absent in the three recipient pre FMT fecal samples (<0.01%). The microbe composition in gnotobiotic mice transplanted with the donor fecal samples was similar to the human samples. The recipient samples contained Enterobacteriaceae, Lactobacillaceae, Enterococcaceae in relative abundance of 43, 11, 8%, respectively. However, gnotobiotic mice transplanted with the recipient fecal samples had an average relative abundance of unclassified Clostridiales of 55%, approximately 7000 times the abundance in the recipient fecal samples prior to transplant. Microbiome analysis of fecal samples from the three patients early (2-4 weeks) after FMT revealed a microbe composition with the relative abundance of both Bacteriodaceae and Lachnospiraceae that was approximately 7% of that of the donor. In contrast, gnotobioitc mice transplanted with the fecal samples obtained from the three at early times post FMT revealed increases in the relative abundance of Bacteriodaceae and Lachnospiraceae microbe compositions to levels similar to the donor fecal samples. Furthermore, the unclassified Clostridiales in the recipient samples post FMT was reduced to an average of 10%.<br><br>CONCLUSION: We have used transplantation into gnotobiotic mice to evaluate the colonization potential of microbiota in FMT patients early after transplant. The commensal microbes present at early times post FMT out competed non-commensal microbes (e.g. such as unclassified Clostridiales) for niche space. The selective advantage of these commensal microbes to occupy niches in the gastrointestinal tract helps to explain the success of FMT to reconstitute the gut microbe community of patients with recurrent C. difficile infections.}, }
@article {pmid26757463, year = {2016}, author = {Lee, CH and Steiner, T and Petrof, EO and Smieja, M and Roscoe, D and Nematallah, A and Weese, JS and Collins, S and Moayyedi, P and Crowther, M and Ropeleski, MJ and Jayaratne, P and Higgins, D and Li, Y and Rau, NV and Kim, PT}, title = {Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.}, journal = {JAMA}, volume = {315}, number = {2}, pages = {142-149}, doi = {10.1001/jama.2015.18098}, pmid = {26757463}, issn = {1538-3598}, mesh = {Aged ; Aged, 80 and over ; *Clostridioides difficile ; *Cryopreservation ; Diarrhea/etiology/*therapy ; Double-Blind Method ; Enterocolitis, Pseudomembranous/complications/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; }, abstract = {IMPORTANCE: Clostridium difficile infection (CDI) is a major burden in health care and community settings. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues. Fecal microbiota transplantation (FMT) is a promising, but not readily available, intervention.<br><br>OBJECTIVE: To determine whether frozen-and-thawed (frozen, experimental) FMT is noninferior to fresh (standard) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT.<br><br>Randomized, double-blind, noninferiority trial enrolling 232 adults with recurrent or refractory CDI, conducted between July 2012 and September 2014 at 6 academic medical centers in Canada.<br><br>INTERVENTIONS: Patients were randomly allocated to receive frozen (n&#x2009;=&#x2009;114) or fresh (n&#x2009;=&#x2009;118) FMT via enema.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events. Noninferiority margin was set at 15%.<br><br>RESULTS: A total of 219 patients (n&#x2009;=&#x2009;108 in the frozen FMT group and n&#x2009;=&#x2009;111 in the fresh FMT group) were included in the modified intention-to-treat (mITT) population and 178 (frozen FMT: n&#x2009;=&#x2009;91, fresh FMT: n&#x2009;=&#x2009;87) in the per-protocol population. In the per-protocol population, the proportion of patients with clinical resolution was 83.5% for the frozen FMT group and 85.1% for the fresh FMT group (difference, -1.6% [95% CI, -10.5% to &#x221e;]; P&#x2009;=&#x2009;.01 for noninferiority). In the mITT population the clinical resolution was 75.0% for the frozen FMT group and 70.3% for the fresh FMT group (difference, 4.7% [95% CI, -5.2% to &#x221e;]; P&#x2009;<&#x2009;.001 for noninferiority). There were no differences in the proportion of adverse or serious adverse events between the treatment groups.<br><br>CONCLUSIONS AND RELEVANCE: Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea. Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting.<br><br>TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01398969.}, }
@article {pmid26757461, year = {2016}, author = {Malani, PN and Rao, K}, title = {Expanded Evidence for Frozen Fecal Microbiota Transplantation for Clostridium difficile Infection: A Fresh Take.}, journal = {JAMA}, volume = {315}, number = {2}, pages = {137-138}, pmid = {26757461}, issn = {1538-3598}, support = {P30 AG024824/AG/NIA NIH HHS/United States ; AG-024824/AG/NIA NIH HHS/United States ; }, mesh = {*Clostridioides difficile ; *Cryopreservation ; Diarrhea/*therapy ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; }, }
@article {pmid26755882, year = {2016}, author = {Mangiola, F and Ianiro, G and Franceschi, F and Fagiuoli, S and Gasbarrini, G and Gasbarrini, A}, title = {Gut microbiota in autism and mood disorders.}, journal = {World journal of gastroenterology}, volume = {22}, number = {1}, pages = {361-368}, pmid = {26755882}, issn = {2219-2840}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/therapeutic use ; Autism Spectrum Disorder/etiology/microbiology/therapy ; Autistic Disorder/etiology/*microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/physiology ; Humans ; Mood Disorders/etiology/*microbiology/therapy ; Probiotics/therapeutic use ; }, abstract = {The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal (GI) system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases. In the last few years, the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism, dementia and mood disorder, has been raised. The evidence of the inflammatory state alteration, highlighted in disorders such as schizophrenia, major depressive disorder and bipolar disorder, strongly recalls the microbiota alteration, highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders. Up to now, available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders. The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date, with few but promising results. A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder (ASD), as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders.}, }
@article {pmid26752703, year = {2016}, author = {Di Lena, M and Porcelli, F and Altomare, DF}, title = {Volatile organic compounds as new biomarkers for colorectal cancer: a review.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {18}, number = {7}, pages = {654-663}, doi = {10.1111/codi.13271}, pmid = {26752703}, issn = {1463-1318}, mesh = {Biomarkers, Tumor/analysis ; Breath Tests/methods ; Colorectal Neoplasms/*diagnosis ; Early Detection of Cancer/*methods ; Feces/chemistry ; Humans ; Reproducibility of Results ; Volatile Organic Compounds/*analysis ; }, abstract = {Analysis of the volatile part of the metabolome (volatile organic compounds, VOC) present in the gas phase of excreted materials is a promising new screening tool for several cancers, including colorectal cancer (CRC). The VOC signature can reflect health status, like a 'fingerprint', and can be modified in several diseases. Technical difficulties still limit the widespread use of VOC analysis in the clinical setting, but this approach has already been applied successfully in the diagnosis of CRC. The present study reviews the available data on VOC present in the headspace (the gaseous constituents of a closed space above a liquid or solid) of blood, urine, faeces and breath as a potential screening tool for CRC. A systematic electronic literature search was conducted in PubMed, Scirus and Google using the following keywords: Metabolomic, Volatile Organic Compounds (VOC), Electronic-nose and Colorectal Cancer. Only articles published in English between 2000 and 2015 were selected and these were independently checked by two of the authors. Ten papers describing the reliability of VOC analysis in breath and faeces, blood and urine were selected; all indicated good reliability in detecting CRC. The use of different substrates and different analytical platforms has led to the identification of different patterns of VOC. The reliability of a metabolomic approach as a noninvasive biomarker for use in CRC screening is supported by this review despite several limitations due to the number of patients included in each study, the different analytical platforms and biological materials used and different VOC identified.}, }
@article {pmid26751143, year = {2016}, author = {Tian, H and Ding, C and Gong, J and Ge, X and McFarland, LV and Gu, L and Wei, Y and Chen, Q and Zhu, W and Li, J and Li, N}, title = {Treatment of Slow Transit Constipation With Fecal Microbiota Transplantation: A Pilot Study.}, journal = {Journal of clinical gastroenterology}, volume = {50}, number = {10}, pages = {865-870}, doi = {10.1097/MCG.0000000000000472}, pmid = {26751143}, issn = {1539-2031}, mesh = {Adult ; Aged ; Constipation/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Pilot Projects ; Prospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been proposed as a therapeutic approach for functional gastrointestinal disease. We launched a clinical study to examine the safety and efficacy of FMT for slow transit constipation (STC).<br><br>MATERIALS AND METHODS: Twenty-four patients with STC, aged from 20 to 74 were enrolled in this prospective open-label study. Patients received FMT on 3 consecutive days through nasojejunal tubes and followed up for 12 weeks after treatment. Rate of clinical improvement and remission, Wexner constipation scale, Bowel movement per week, and gastrointestinal quality-of-life index were evaluated.<br><br>RESULTS: The rate of clinical improvement and remission based on clinical activity at week 12 was 50% (12/24) and 37.5% (9/24), respectively. The patient's stool frequency increased from a mean of 1.8 (SD 1.3) per week pre-FMT to 4.1 (SD 2.6) at week 12 post-FMT without laxative usage (P<0.01). The stool consistency showed a tendency to improve after FMT administration. Comparison of pre-FMT and post-FMT Wexner constipation scores demonstrated a significant reduction between baseline (14.1&#xb1;3.3) and the first week (9.8&#xb1;4.9), which was maintained up to the following 12 weeks (7.5&#xb1;3.2; P<0.01). Compared with baseline, significant overall improvements were also seen in gastrointestinal quality-of-life index score at week 1, week 2, week 4, week 8, and week 12 of follow-up (P<0.01). The improvements were accompanied by the decline of colonic transit time. No severe adverse events during the whole FMT procedure follow-up except for venting (6/24), abdominal pain (3/24), bloating (2/24), and diarrhea (7/24).<br><br>CONCLUSION: This is a pilot study demonstrating that FMT was safe and may have the potential to improve symptoms in patients with STC.}, }
@article {pmid26749902, year = {2015}, author = {Meri, S and de Vos, W}, title = {[Structure and function of intestinal microbiota in health and disease--130 years after Theodor Escherich].}, journal = {Duodecim; laaketieteellinen aikakauskirja}, volume = {131}, number = {22}, pages = {2091-2098}, pmid = {26749902}, issn = {0012-7183}, mesh = {Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/immunology/*physiology ; Humans ; }, abstract = {Since early life we are colonized by developing communities of microbes that dominate our body in great numbers. In the intestinal tract they constitute the largest microbial ecosystem close to our heart: our microbes inside. Recent studies have shown that these microbes, collectively termed microbiota, are essential for our health through interacting with our gut, gut-liver and gut-brain axis, and our immune system. Hence this contribution deals with these aspects and provides an overview of the structure and function of the microbiota as well as the impact on future therapies ranging from fecal transplantations to the use of a synthetic microbiome.}, }
@article {pmid29067182, year = {2016}, author = {Schmitz, S and Suchodolski, J}, title = {Understanding the canine intestinal microbiota and its modification by pro-, pre- and synbiotics - what is the evidence?.}, journal = {Veterinary medicine and science}, volume = {2}, number = {2}, pages = {71-94}, pmid = {29067182}, issn = {2053-1095}, abstract = {Interest in the composition of the intestinal microbiota and possibilities of its therapeutic modifications has soared over the last decade and more detailed knowledge specific to the canine microbiota at different mucosal sites including the gut is available. Probiotics, prebiotics or their combination (synbiotics) are a way of modifying the intestinal microbiota and exert effects on the host immune response. Probiotics are proposed to exert their beneficial effects through various pathways, for example production of antimicrobial peptides, enhancing growth of favourable endogenous microorganisms, competition for epithelial colonisation sites and immune-modulatory functions. Despite widespread use of pro-, pre- and synbiotics, scientific evidence of their beneficial effects in different conditions of the dog is scarce. Specific effects of different strains, their combination or their potential side-effects have not been evaluated sufficiently. In some instances, in vitro results have been promising, but could not be transferred consistently into in vivo situations. Specific canine gastrointestinal (GI) diseases or conditions where probiotics would be beneficial, their most appropriate dosage and application have not been assessed extensively. This review summarises the current knowledge of the intestinal microbiome composition in the dog and evaluates the evidence for probiotic use in canine GI diseases to date. It wishes to provide veterinarians with evidence-based information on when and why these products could be useful in preventing or treating canine GI conditions. It also outlines knowledge about safety and approval of commercial probiotic products, and the potential use of faecal microbial transplantation, as they are related to the topic of probiotic usage.}, }
@article {pmid26749318, year = {2016}, author = {Landman, C and Quévrain, E}, title = {[Gut microbiota: Description, role and pathophysiologic implications].}, journal = {La Revue de medecine interne}, volume = {37}, number = {6}, pages = {418-423}, doi = {10.1016/j.revmed.2015.12.012}, pmid = {26749318}, issn = {1768-3122}, mesh = {Dysbiosis/*complications/metabolism/microbiology/pathology ; Gastrointestinal Microbiome/*physiology ; Humans ; Immune System/microbiology ; Infant, Newborn ; Inflammatory Bowel Diseases/metabolism/microbiology/pathology ; Intestinal Mucosa/metabolism ; Intestines/*microbiology/*pathology ; Obesity/metabolism/microbiology ; }, abstract = {The human gut contains 10(14) bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real "hidden organ". In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads.}, }
@article {pmid26746170, year = {2016}, author = {Sokol, H}, title = {Toward Rational Donor Selection in Faecal Microbiota Transplantation for IBD.}, journal = {Journal of Crohn's &amp; colitis}, volume = {10}, number = {4}, pages = {375-376}, pmid = {26746170}, issn = {1876-4479}, mesh = {Clostridioides difficile ; *Donor Selection ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Microbiota ; }, }
@article {pmid26744774, year = {2016}, author = {Lundberg, R and Toft, MF and August, B and Hansen, AK and Hansen, CH}, title = {Antibiotic-treated versus germ-free rodents for microbiota transplantation studies.}, journal = {Gut microbes}, volume = {7}, number = {1}, pages = {68-74}, pmid = {26744774}, issn = {1949-0984}, mesh = {Animals ; Anti-Bacterial Agents/*administration &amp; dosage ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*drug effects ; Gastrointestinal Tract/*microbiology ; Mice ; Models, Animal ; Reproducibility of Results ; *Specific Pathogen-Free Organisms ; }, abstract = {We recently investigated the applicability of antibiotic-treated recipient mice for transfer of different gut microbiota profiles. With this addendum we elaborate on perspectives and limitations of using antibiotics as an alternative to germ-free (GF) technology in microbial transplantation studies, and we speculate on the housing effect. It is possible to transfer host phenotypes via fecal transplantation to antibiotic-treated animals, but problems with reproducibility, baseline values, and antibiotic resistance genes should be considered. GF animals maintained in isolators still seem to be the best controlled models for long-term microbial transplantation, but antibiotic-treated recipients are also commonly utilized. We identify a need for systematic experiments investigating the stability of microbial transplantations by addressing 1) the recipient status as either GF, antibiotic-treated or specific pathogen free and 2) different levels of protected housing systems. In addition, the developmental effect of microbes on host physiological functions should be evaluated in the different scenarios.}, }
@article {pmid26743554, year = {2016}, author = {Asonuma, K and Kuroki, Y and Ino, S and Hanamura, S and Takano, Y and Yamamura, E and Gomi, K and Nagahama, M and Inoue, K and Takahashi, H}, title = {[Severe refractory Clostridium difficile infection with good response to fecal microbiota transplantation: a case report].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {113}, number = {1}, pages = {55-62}, doi = {10.11405/nisshoshi.113.55}, pmid = {26743554}, issn = {0446-6586}, mesh = {Abdominal Pain/etiology ; *Clostridioides difficile ; Diarrhea/etiology ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Female ; Fever/etiology ; Humans ; Middle Aged ; }, abstract = {A 49-year-old woman diagnosed with pseudomembranous enterocolitis was transferred to our hospital for medical treatment. She responded poorly to treatment with vancomycin hydrochloride and metronidazole, so she underwent fecal microbiota transplantation. Treatment effects were observed the next day, and the diarrhea disappeared within 3 days. Colonoscopy 4 days later revealed the resolution of pseudomembranes, and no recurrences were reported within the first year after discharge.}, }
@article {pmid26742586, year = {2016}, author = {Agus, A and Denizot, J and Thévenot, J and Martinez-Medina, M and Massier, S and Sauvanet, P and Bernalier-Donadille, A and Denis, S and Hofman, P and Bonnet, R and Billard, E and Barnich, N}, title = {Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {19032}, pmid = {26742586}, issn = {2045-2322}, mesh = {Animals ; Bacterial Adhesion/drug effects ; Benzeneacetamides/pharmacology ; Colitis/chemically induced/genetics/*microbiology/prevention &amp; control ; Crohn Disease/etiology/genetics/microbiology/prevention &amp; control ; Diet, High-Fat/adverse effects ; Diet, Western/*adverse effects ; Dietary Sucrose/adverse effects ; *Disease Susceptibility ; Dysbiosis/*etiology/genetics/microbiology/prevention &amp; control ; Escherichia coli/growth &amp; development/metabolism/pathogenicity ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects ; Gene Expression Regulation ; Gene-Environment Interaction ; Humans ; Intestinal Mucosa/drug effects/microbiology/pathology ; Male ; Mice ; Receptors, G-Protein-Coupled/agonists/*genetics/metabolism ; Sodium Dodecyl Sulfate ; }, abstract = {Recent advances have shown that the abnormal inflammatory response observed in CD involves an interplay among intestinal microbiota, host genetics and environmental factors. The escalating consumption of fat and sugar in Western countries parallels an increased incidence of CD during the latter 20(th) century. The impact of a HF/HS diet in mice was evaluated for the gut micro-inflammation, intestinal microbiota composition, function and selection of an E. coli population. The HF/HS diet created a specific inflammatory environment in the gut, correlated with intestinal mucosa dysbiosis characterized by an overgrowth of pro-inflammatory Proteobacteria such as E. coli, a decrease in protective bacteria, and a significantly decreased of SCFA concentrations. The expression of GPR43, a SCFA receptor was reduced in mice treated with a HF/HS diet and reduced in CD patients compared with controls. Interestingly, mice treated with an agonist of GPR43 were protected against DSS-induced colitis. Finally, the transplantation of feces from HF/HS treated mice to GF mice increased susceptibility to AIEC infection. Together, our results demonstrate that a Western diet could aggravate the inflammatory process and that the activation of the GPR43 receptor pathway could be used as a new strategy to treat CD patients.}, }
@article {pmid26741111, year = {2016}, author = {Lauro, A and Marino, IR and Matsumoto, CS}, title = {Advances in allograft monitoring after intestinal transplantation.}, journal = {Current opinion in organ transplantation}, volume = {21}, number = {2}, pages = {165-170}, doi = {10.1097/MOT.0000000000000279}, pmid = {26741111}, issn = {1531-7013}, mesh = {Biomarkers/analysis ; Feces/chemistry ; Graft Rejection/immunology ; Humans ; Intestinal Diseases/*surgery ; Intestines/*transplantation ; Transplantation, Homologous ; }, abstract = {PURPOSE OF REVIEW: The intestinal allograft, with an enormous lymphoid load, is a highly immunogenic organ which elicits a strong alloimmune response. In the early posttransplant period, a robust graft biopsy protocol via a temporary ileostomy is utilized for surveillance to detect rejection. In the later posttransplant period, after enteral continuity is reestablished, graft biopsies via a colonoscopy become more cumbersome. Alternative methods for intestinal allograft monitoring other than graft biopsy are of particular interest.<br><br>RECENT FINDINGS: Biomarkers and diagnostic tools, such as granzyme B, perforin, fecal calprotectin, citrulline, donor-specific antibody, and zoom video endoscopy have all been studied for application as reliable methods of performing intestinal allograft surveillance. Each modality has the capability to monitor a separate and unique process in the host-allograft immune response.<br><br>SUMMARY: The goal to find a reliable, reproducible, and noninvasive method for intestinal graft monitoring remains an elusive one. Many of the current modalities available only serve to act as complementary tests in conjunction with astute clinical observations. Graft biopsy remains the gold standard for monitoring the intestinal allograft.}, }
@article {pmid26740296, year = {2017}, author = {Parséus, A and Sommer, N and Sommer, F and Caesar, R and Molinaro, A and Ståhlman, M and Greiner, TU and Perkins, R and Bäckhed, F}, title = {Microbiota-induced obesity requires farnesoid X receptor.}, journal = {Gut}, volume = {66}, number = {3}, pages = {429-437}, pmid = {26740296}, issn = {1468-3288}, support = {615362/ERC_/European Research Council/International ; }, mesh = {Adipose Tissue/pathology ; Animals ; Bile Acids and Salts/metabolism ; Cecum/microbiology ; Dietary Fats/administration &amp; dosage ; Fatty Liver/*etiology/metabolism ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Gene Expression ; *Germ-Free Life ; Glucose/metabolism ; Inflammation/etiology ; Insulin-Secreting Cells/pathology ; Macrophages ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/complications/*metabolism/*microbiology ; Phenotype ; Receptors, Cytoplasmic and Nuclear/*genetics/*metabolism ; Weight Gain ; }, abstract = {OBJECTIVE: The gut microbiota has been implicated as an environmental factor that modulates obesity, and recent evidence suggests that microbiota-mediated changes in bile acid profiles and signalling through the bile acid nuclear receptor farnesoid X receptor (FXR) contribute to impaired host metabolism. Here we investigated if the gut microbiota modulates obesity and associated phenotypes through FXR.<br><br>DESIGN: We fed germ-free (GF) and conventionally raised (CONV-R) wild-type and Fxr-/- mice a high-fat diet (HFD) for 10&#x2005;weeks. We monitored weight gain and glucose metabolism and analysed the gut microbiota and bile acid composition, beta-cell mass, accumulation of macrophages in adipose tissue, liver steatosis, and expression of target genes in adipose tissue and liver. We also transferred the microbiota of wild-type and Fxr-deficient mice to GF wild-type mice.<br><br>RESULTS: The gut microbiota promoted weight gain and hepatic steatosis in an FXR-dependent manner, and the bile acid profiles and composition of faecal microbiota differed between Fxr-/- and wild-type mice. The obese phenotype in colonised wild-type mice was associated with increased beta-cell mass, increased adipose inflammation, increased steatosis and expression of genes involved in lipid uptake. By transferring the caecal microbiota from HFD-fed Fxr-/- and wild-type mice into GF mice, we showed that the obesity phenotype was transferable.<br><br>CONCLUSIONS: Our results indicate that the gut microbiota promotes diet-induced obesity and associated phenotypes through FXR, and that FXR may contribute to increased adiposity by altering the microbiota composition.}, }
@article {pmid26724298, year = {2016}, author = {Bridges, E and McNeill, M and Munro, N}, title = {Research in Review: Driving Critical Care Practice Change.}, journal = {American journal of critical care : an official publication, American Association of Critical-Care Nurses}, volume = {25}, number = {1}, pages = {76-84}, doi = {10.4037/ajcc2016564}, pmid = {26724298}, issn = {1937-710X}, mesh = {Anti-Infective Agents, Local/therapeutic use ; Baths/*methods ; Burnout, Professional/epidemiology ; Chlorhexidine/therapeutic use ; Clinical Trials as Topic/ethics ; *Clostridioides difficile ; Compassion Fatigue/epidemiology ; Critical Care/*methods ; Cross Infection/prevention &amp; control ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; False Positive Reactions ; Fecal Microbiota Transplantation ; Hemorrhagic Fever, Ebola/drug therapy/prevention &amp; control ; Humans ; Medical Futility/psychology ; Monitoring, Physiologic ; Shock, Septic/therapy ; Signal Detection, Psychological ; Thirst ; Tourniquets ; Vaccines ; Wounds and Injuries/therapy ; }, abstract = {During the past year, studies were published that will lead to practice change, address challenges at the bedside, and introduce new care strategies. This article summarizes some of this important work and considers it in the context of previous research and practice. Examples of research-based practice changes include the performance and assessment of septic shock resuscitation, and the integration of tourniquets and massive transfusions in civilian trauma. Care challenges addressed include ethical considerations in light of the Ebola epidemic, infection prevention associated with chlorhexidine bathing, bedside alarm management, evidence to enhance moral courage, and interventions to mitigate thirst in critically ill patients. Research that portends future care includes a discussion of fecal microbiota transplant for patients with refractory infection with refractory infection with Clostridium difficile.}, }
@article {pmid28635818, year = {2016}, author = {Drapkina, OM and Korneeva, ON}, title = {[Gut microbiota and obesity: Pathogenetic relationships and ways to normalize the intestinal microflora].}, journal = {Terapevticheskii arkhiv}, volume = {88}, number = {9}, pages = {135-142}, doi = {10.17116/terarkh2016889135-142}, pmid = {28635818}, issn = {0040-3660}, mesh = {Diabetes Mellitus ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Humans ; Obesity/*microbiology ; Prebiotics ; Probiotics/*therapeutic use ; }, abstract = {The review demonstrates mechanisms in the relationship of obesity to gut microbiota, as well as possible therapeutic measures to normalize the intestinal microflora. There is evidence that the latter makes a great contribution to the pathogenesis of obesity and related diseases. Investigations have shown the role of the nature of consumed foods (fatty foods) in reducing the amount of bifidobacteria and lactobacilli, as well as the effects of bacterial lipopolysaccharides and metabolites from the intestinal microflora (trimethylamine-N-oxide, bile acids, etc.). The use of prebiotics, probiotics and ursodeoxycholic acid preparations and fecal transplantation are promising in correcting the microflora and in providing their positive effect on metabolic disturbances. Certain probiotic strains are effective in treating dyslipidemia, diabetes mellitus, obesity, and metabolic syndrome. Gut microbiota is impaired in obesity and contributes to the development of cardiovascular diseases. The control of the gut microbiota and the use of drugs altering the composition of the microflora may become a novel approach to reducing the risk of cardiovascular diseases.}, }
@article {pmid28525191, year = {2016}, author = {Haemers, I and Delvallée, M}, title = {[Fecal microbiota transplant in the treatment of recurrent Clostridium difficile infection: A case report].}, journal = {Revue medicale de Bruxelles}, volume = {37}, number = {3}, pages = {174-177}, pmid = {28525191}, issn = {0035-3639}, mesh = {Clostridioides difficile/*growth &amp; development ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridium difficile infection is a major cause of nosocomial diarrhea. Its incidence has increased in the past 20 years and is associated with a significant morbidity and mortality. Relapsing is frequent after treatment and the management of these recurrent Clostridium difficile infections is challenging. Several studies over the years have shown that fecal microbiota transplantion is associated with a high degree of success. Fecal microbiota transplantion is now part of the European recommendations in the treatment of recurrent Clostridium difficile infections. However, standard procedures are needed to define indications, donor's selection criteria, preparation of the stool sample and its administration as well as the patients follow up. Illustration by a case report.}, }
@article {pmid28525185, year = {2016}, author = {Van Laethem, Y}, title = {[Not Available].}, journal = {Revue medicale de Bruxelles}, volume = {37}, number = {3}, pages = {133-134}, pmid = {28525185}, issn = {0035-3639}, mesh = {*Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; }, }
@article {pmid26719306, year = {2016}, author = {Kabeerdoss, J and Sandhya, P and Danda, D}, title = {Gut inflammation and microbiome in spondyloarthritis.}, journal = {Rheumatology international}, volume = {36}, number = {4}, pages = {457-468}, pmid = {26719306}, issn = {1437-160X}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bacteria/immunology/*pathogenicity ; Cytokines/immunology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Inflammation Mediators/immunology ; Inflammatory Bowel Diseases/immunology/microbiology ; Intestines/*microbiology ; Prebiotics ; Probiotics/therapeutic use ; Signal Transduction ; Spondylarthritis/immunology/*microbiology/therapy ; }, abstract = {Spondyloarthritis (SpA) is chronic inflammatory disease involving joints and the spine. Bowel inflammation is common in SpA, which may be classified as acute or chronic. Chronic gut inflammation is most common in SpA patients with axial involvement as compared to those presenting with peripheral involvement alone. The pathogenesis of gut inflammation in SpA could be explained by two factors-over-activation of immunological cells and altered gut microbiome. This is exemplified by SpA animal models, namely HLA-B27-expressing transgenic animals and SKG mice models. Immunological mechanisms include homing of activated T cells from gut into synovium, excess pro-inflammatory cytokines secretion by immune cells such as IL-23 and genetic variations in immunological genes. The evidence for role of gut microbiome in SpA is gradually emerging. Recently, metagenomic study of gut microbiome by sequencing of microbial nucleic acids has enabled identification of new microbial taxa and their functions in gut of patients with SpA. In SpA, the gut microbiome could emerge as diagnostic and prognostic marker of disease. Modulation of gut microbiome is slated to have therapeutic potential as well.}, }
@article {pmid26718401, year = {2016}, author = {Ranjan, R and Rani, A and Metwally, A and McGee, HS and Perkins, DL}, title = {Analysis of the microbiome: Advantages of whole genome shotgun versus 16S amplicon sequencing.}, journal = {Biochemical and biophysical research communications}, volume = {469}, number = {4}, pages = {967-977}, pmid = {26718401}, issn = {1090-2104}, support = {R01 AI053878/AI/NIAID NIH HHS/United States ; R01 HL081663/HL/NHLBI NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/isolation &amp; purification ; Base Sequence ; Chromosome Mapping/*methods ; DNA, Bacterial/*genetics ; Humans ; Metagenome/*genetics ; Microbiota/*genetics ; Molecular Sequence Data ; RNA, Ribosomal, 16S/*genetics ; Reproducibility of Results ; Sensitivity and Specificity ; Sequence Analysis, DNA/*methods ; }, abstract = {The human microbiome has emerged as a major player in regulating human health and disease. Translational studies of the microbiome have the potential to indicate clinical applications such as fecal transplants and probiotics. However, one major issue is accurate identification of microbes constituting the microbiota. Studies of the microbiome have frequently utilized sequencing of the conserved 16S ribosomal RNA (rRNA) gene. We present a comparative study of an alternative approach using whole genome shotgun sequencing (WGS). In the present study, we analyzed the human fecal microbiome compiling a total of 194.1 × 10(6) reads from a single sample using multiple sequencing methods and platforms. Specifically, after establishing the reproducibility of our methods with extensive multiplexing, we compared: 1) The 16S rRNA amplicon versus the WGS method, 2) the Illumina HiSeq versus MiSeq platforms, 3) the analysis of reads versus de novo assembled contigs, and 4) the effect of shorter versus longer reads. Our study demonstrates that whole genome shotgun sequencing has multiple advantages compared with the 16S amplicon method including enhanced detection of bacterial species, increased detection of diversity and increased prediction of genes. In addition, increased length, either due to longer reads or the assembly of contigs, improved the accuracy of species detection.}, }
@article {pmid26717934, year = {2016}, author = {Orduña, P and Lopez, SY and Schmulson, M and Arredondo, R and de Leon, SP and Lopez-Vidal, Y}, title = {Corrigendum: A Survey Using the Social Networks Revealed Poor Knowledge on Fecal Microbiota Transplantation.}, journal = {Journal of neurogastroenterology and motility}, volume = {22}, number = {1}, pages = {161}, doi = {10.5056/jnm22011}, pmid = {26717934}, issn = {2093-0879}, abstract = {This article was initially published on the Journal of Neurogastroenterology and Motility with omission of a funding source. The funding source should be added as the following: "Financial support: This work was supported by DGAPA PAPPIT UNAM (IV200315)."}, }
@article {pmid26711839, year = {2016}, author = {Dalton, HR and Kamar, N and van Eijk, JJ and Mclean, BN and Cintas, P and Bendall, RP and Jacobs, BC}, title = {Hepatitis E virus and neurological injury.}, journal = {Nature reviews. Neurology}, volume = {12}, number = {2}, pages = {77-85}, pmid = {26711839}, issn = {1759-4766}, mesh = {Animals ; Hepatitis E/epidemiology/*physiopathology/*therapy ; *Hepatitis E virus ; Humans ; Peripheral Nervous System Diseases/epidemiology/physiopathology/*therapy/*virology ; }, abstract = {Hepatitis E is hyperendemic in many developing countries in Asia and Africa, and is caused by hepatitis E virus (HEV) genotypes 1 and 2, which are spread via the faecal-oral route by contaminated water. Recent data show that HEV infection is also endemic in developed countries. In such geographical settings, hepatitis E is caused by HEV genotypes 3 and 4, and is mainly a porcine zoonosis. In a minority of cases, HEV causes acute and chronic hepatitis, but infection is commonly asymptomatic or unrecognized. HEV infection is associated with a number of extrahepatic manifestations, including a range of neurological injuries. To date, 91 cases of HEV-associated neurological injury--most commonly, Guillain-Barré syndrome, neuralgic amyotrophy, and encephalitis/myelitis--have been reported. Here, we review the reported cases, discuss possible pathogenic mechanisms, and present our perspectives on future directions and research questions.}, }
@article {pmid26711754, year = {2015}, author = {Rocha-Pereira, J and Van Dycke, J and Neyts, J}, title = {Treatment with a Nucleoside Polymerase Inhibitor Reduces Shedding of Murine Norovirus in Stool to Undetectable Levels without Emergence of Drug-Resistant Variants.}, journal = {Antimicrobial agents and chemotherapy}, volume = {60}, number = {3}, pages = {1907-1911}, pmid = {26711754}, issn = {1098-6596}, mesh = {Amides/therapeutic use ; Animals ; Caliciviridae Infections/*drug therapy/virology ; Cytidine/*analogs &amp; derivatives/therapeutic use ; Disease Models, Animal ; Feces/virology ; Gastroenteritis/*drug therapy/virology ; Mice ; Mice, Knockout ; Norovirus/*drug effects/growth &amp; development ; Pyrazines/therapeutic use ; Receptors, Interferon/genetics ; Transplant Recipients ; Virus Shedding/*drug effects ; }, abstract = {Prolonged norovirus shedding may occur in certain patients, such as organ transplant recipients. We established a mouse model for persistent norovirus infection (using the mouse norovirus MNV.CR6 strain). The nucleoside viral polymerase inhibitor 2'-C-methylcytidine (2CMC), but not favipiravir (T-705), reduced viral shedding to undetectable levels. Viral rebound was observed after stopping treatment, which was again effectively controlled by treatment with 2CMC. No drug-resistant variants emerged.}, }
@article {pmid26711739, year = {2016}, author = {Durgan, DJ and Ganesh, BP and Cope, JL and Ajami, NJ and Phillips, SC and Petrosino, JF and Hollister, EB and Bryan, RM}, title = {Role of the Gut Microbiome in Obstructive Sleep Apnea-Induced Hypertension.}, journal = {Hypertension (Dallas, Tex. : 1979)}, volume = {67}, number = {2}, pages = {469-474}, pmid = {26711739}, issn = {1524-4563}, support = {R21 NS094806/NS/NINDS NIH HHS/United States ; R01 NS080531/NS/NINDS NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; DK56338/DK/NIDDK NIH HHS/United States ; R01NS080531/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Blood Pressure/*physiology ; Disease Models, Animal ; Dysbiosis/*complications/microbiology ; Gastrointestinal Microbiome/*physiology ; Hypertension/*etiology/physiopathology ; Male ; Polysomnography ; Rats ; Rats, Long-Evans ; Sleep/*physiology ; Sleep Apnea Syndromes/*complications/microbiology/physiopathology ; }, abstract = {Individuals suffering from obstructive sleep apnea (OSA) are at increased risk for systemic hypertension. The importance of a healthy gut microbiota, and detriment of a dysbiotic microbiota, on host physiology is becoming increasingly evident. We tested the hypothesis that gut dysbiosis contributes to hypertension observed with OSA. OSA was modeled in rats by inflating a tracheal balloon during the sleep cycle (10-s inflations, 60 per hour). On normal chow diet, OSA had no effect on blood pressure; however, in rats fed a high-fat diet, blood pressure increased 24 and 29 mm Hg after 7 and 14 days of OSA, respectively (P<0.05 each). Bacterial community characterization was performed on fecal pellets isolated before and after 14 days of OSA in chow and high-fat fed rats. High-fat diet and OSA led to significant alterations of the gut microbiota, including decreases in bacterial taxa known to produce the short chain fatty acid butyrate (P<0.05). Finally, transplant of dysbiotic cecal contents from hypertensive OSA rats on high-fat diet into OSA recipient rats on normal chow diet (shown to be normotensive) resulted in hypertension similar to that of the donor (increased 14 and 32 mm Hg after 7 and 14 days of OSA, respectively; P<0.05). These studies demonstrate a causal relationship between gut dysbiosis and hypertension, and suggest that manipulation of the microbiota may be a viable treatment for OSA-induced, and possibly other forms of, hypertension.}, }
@article {pmid26711435, year = {2016}, author = {Kosulin, K and Geiger, E and Vécsei, A and Huber, WD and Rauch, M and Brenner, E and Wrba, F and Hammer, K and Innerhofer, A and Pötschger, U and Lawitschka, A and Matthes-Leodolter, S and Fritsch, G and Lion, T}, title = {Persistence and reactivation of human adenoviruses in the gastrointestinal tract.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {22}, number = {4}, pages = {381.e1-381.e8}, doi = {10.1016/j.cmi.2015.12.013}, pmid = {26711435}, issn = {1469-0691}, mesh = {Adenoviridae Infections ; Adenoviruses, Human/*isolation &amp; purification/*physiology ; Adolescent ; Biopsy ; Child ; Child, Preschool ; Feces/virology ; Female ; Gastrointestinal Tract/*virology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunocompromised Host ; Infant ; Intestinal Mucosa/virology ; Lymphocytes/virology ; Male ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; *Virus Activation ; Young Adult ; }, abstract = {Reactivation of persistent human adenoviruses (HAdVs) is associated with high morbidity and mortality in paediatric haematopoietic stem cell transplant (HSCT) recipients. Although invasive HAdV infections mainly arise from the gastrointestinal (GI) tract, the specific sites of HAdV persistence are not well characterised. We prospectively screened biopsies from 143 non-HSCT paediatric patients undergoing GI endoscopy and monitored serial stool specimens from 148 paediatric HSCT recipients for the presence of HAdV by real-time PCR. Persistence of HAdV in the GI tract was identified in 31% of children, with the highest prevalence in the terminal ileum. In situ hybridisation and immunohistochemistry identified HAdV persistence in lymphoid cells of the lamina propria, whereas biopsies from five transplant recipients revealed high numbers of replicating HAdV in intestinal epithelial cells. The prevalence of HAdV species, the frequencies of persistence in the GI tract and reactivations post transplant indicated a correlation of intestinal HAdV shedding pre-transplant with high risk of invasive infection. HAdV persistence in the GI tract is a likely origin of infectious complications in immunocompromised children. Intestinal lymphocytes represent a reservoir for HAdV persistence and reactivation, whereas the intestinal epithelium is the main site of viral proliferation preceding dissemination. The findings have important implications for assessing the risk of life-threatening invasive HAdV infections.}, }
@article {pmid26708682, year = {2016}, author = {Halmos, T and Suba, I}, title = {[Physiological patterns of intestinal microbiota. The role of dysbacteriosis in obesity, insulin resistance, diabetes and metabolic syndrome].}, journal = {Orvosi hetilap}, volume = {157}, number = {1}, pages = {13-22}, doi = {10.1556/650.2015.30296}, pmid = {26708682}, issn = {0030-6002}, mesh = {Brain/metabolism ; Circadian Rhythm ; Diabetes Mellitus/metabolism/*microbiology ; Dysbiosis/metabolism/microbiology/physiopathology ; Endotoxemia/etiology/metabolism ; Fecal Microbiota Transplantation ; Feeding Behavior ; *Gastrointestinal Microbiome ; Humans ; Inflammation/metabolism/microbiology ; Inflammatory Bowel Diseases/metabolism/microbiology ; *Insulin Resistance ; Intestines/*microbiology ; Metabolic Syndrome/metabolism/*microbiology ; Microbiota ; Obesity/metabolism/*microbiology ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; }, abstract = {The intestinal microbiota is well-known for a long time, but due to newly recognized functions, clinician's attention has turned to it again in the last decade. About 100 000 billion bacteria are present in the human intestines. The composition of bacteriota living in diverse parts of the intestinal tract is variable according to age, body weight, geological site, and diet as well. Normal bacteriota defend the organism against the penetration of harmful microorganisms, and has many other functions in the gut wall integrity, innate immunity, insulin sensitivity, metabolism, and it is in cross-talk with the brain functions as well. It's a recent recognition, that intestinal microbiota has a direct effect on the brain, and the brain also influences the microbiota. This two-way gut-brain axis consists of microbiota, immune and neuroendocrine system, as well as of the autonomic and central nervous system. Emerging from fermentation of carbohydrates, short-chain fatty acids develop into the intestines, which produce butyrates, acetates and propionates, having favorable effects on different metabolic processes. Composition of the intestinal microbiota is affected by the circadian rhythm, such as in shift workers. Dysruption of circadian rhythm may influence intestinal microbiota. The imbalance between the microbiota and host organism leads to dysbacteriosis. From the membrane of Gram-negative bacteria lipopolysacharides penetrate into the blood stream, via impaired permeability of the intestinal mucosa. These processes induce metabolic endotoxaemia, inflammation, impaired glucose metabolism, insulin resistance, obesity, and contribute to the development of metabolic syndrome, type 2 diabetes, inflammarory bowel diseases, autoimmunity and carcinogenesis. Encouraging therapeutic possibility is to restore the normal microbiota either using pro- or prebiotics, fecal transplantation or bariatric surgery. Human investigations seem to prove that fecal transplant from lean healthy individuals into obese diabetic patients improved all the pathological parameters. Wide spread use of bariatric surgery altered gut microbiota and improved metabolic parameters apart from surgery itself. Pathomechanism is not yet completely clarified. Clinicians hope, that deeper understanding of complex functions of intestinal microbiota will contribute to develop more effective therapeutic proceedings against diabetes, metabolic syndrome, and obesity.}, }
@article {pmid26697583, year = {2015}, author = {Popa, D and Laszlo, M and Ciobanu, L and Ucenic, E and Mihalache, M and Pascu, O}, title = {Self-Administered Home Series Fecal "Minitransplants" for Recurrent Clostridium difficile Infection on a Rectal Remnant.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {24}, number = {4}, pages = {531-533}, doi = {10.15403/jgld.2014.1121.244.clo}, pmid = {26697583}, issn = {1842-1121}, mesh = {Aged ; Anti-Infective Agents/administration &amp; dosage ; Clostridioides difficile/drug effects/*pathogenicity ; Colectomy/*adverse effects ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*surgery ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Megacolon, Toxic/diagnosis/microbiology/*surgery ; Metronidazole/administration &amp; dosage ; Proctoscopy ; Recurrence ; *Self Care ; Treatment Outcome ; Vaginal Diseases/microbiology/therapy ; }, abstract = {A fecal microbiota transplant has proved to be an extremely effective method for patients with recurrent infections with Clostridium difficile. We present the case of a 65-year-old female patient with multiple Clostridium difficile infection (CDI) relapses on the rectal remnant, post-colectomy for a CDI-related toxic megacolon. The patient also evidenced associated symptomatic Clostridium difficile vaginal infection. She was successfully treated with serial fecal "minitransplants" (self-administered at home) and metronidazole ovules.}, }
@article {pmid26696614, year = {2016}, author = {Edelstein, C and Daw, JR and Kassam, Z}, title = {Seeking safe stool: Canada needs a universal donor model.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {188}, number = {17-18}, pages = {E431-E432}, pmid = {26696614}, issn = {1488-2329}, mesh = {Biological Specimen Banks ; Canada ; *Directed Tissue Donation ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/*methods ; *Health Policy ; Humans ; *Physician's Role ; Recurrence ; Tissue Donors ; }, }
@article {pmid26695364, year = {2015}, author = {Qian, LL and Li, HT and Zhang, L and Fang, QC and Jia, WP}, title = {Effect of the Gut Microbiota on Obesity and Its Underlying Mechanisms: an Update.}, journal = {Biomedical and environmental sciences : BES}, volume = {28}, number = {11}, pages = {839-847}, doi = {10.3967/bes2015.117}, pmid = {26695364}, issn = {0895-3988}, mesh = {Animals ; Bacterial Translocation ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Insulin Resistance ; Obesity/*microbiology/therapy ; Probiotics/therapeutic use ; }, }
@article {pmid28943629, year = {2015}, author = {Aw, W and Fukuda, S}, title = {An Integrated Outlook on the Metagenome and Metabolome of Intestinal Diseases.}, journal = {Diseases (Basel, Switzerland)}, volume = {3}, number = {4}, pages = {341-359}, pmid = {28943629}, issn = {2079-9721}, abstract = {Recently, metagenomics and metabolomics are the two most rapidly advancing "omics" technologies. Metagenomics seeks to characterize the composition of microbial communities, their operations, and their dynamically co-evolving relationships with the habitats they occupy, whereas metabolomics studies unique chemical endpoints (metabolites) that specific cellular processes leave behind. Remarkable progress in DNA sequencing and mass spectrometry technologies has enabled the comprehensive collection of information on the gut microbiome and its metabolome in order to assess the influence of the gut microbiota on host physiology on a whole-systems level. Our gut microbiota, which consists of prokaryotic cells together with its metabolites, creates a unique gut ecosystem together with the host eukaryotic cells. In this review, we will highlight the detailed relationships between gut microbiota and its metabolites on host health and the pathogenesis of various intestinal diseases such as inflammatory bowel disease and colorectal cancer. Therapeutic interventions such as probiotic and prebiotic administrations and fecal microbiota transplantations will also be discussed. We would like to promote this unique biology-wide approach of incorporating metagenome and metabolome information as we believe that this can help us understand the intricate interplay between gut microbiota and host metabolism to a greater extent. This novel integration of microbiome, metatranscriptome, and metabolome information will help us have an improved holistic understanding of the complex mammalian superorganism, thereby allowing us to gain new and unprecedented insights to providing exciting novel therapeutic approaches for optimal intestinal health.}, }
@article {pmid28868417, year = {2015}, author = {Carmo, J and Marques, S and Chapim, I and Túlio, MA and Rodrigues, JP and Bispo, M and Chagas, C}, title = {Leaping Forward in the Treatment of Clostridium Difficile Infection: Update in 2015.}, journal = {GE Portuguese journal of gastroenterology}, volume = {22}, number = {6}, pages = {259-267}, pmid = {28868417}, issn = {2341-4545}, abstract = {In recent years, significant advances in the treatment of Clostridium difficile infection (CDI) have risen. We review the most relevant updated recommendations in the current standard of care of CDI and discuss emerging therapies, including antibiotic, alternative therapies (probiotics, toxin-binding resins, immunotherapy) and new data on fecal transplantation. Upcoming surgical options and other rescue therapies for severe refractory disease are also addressed. Although oral metronidazole is a first-line therapy for non-severe CDI, emerging data have demonstrated its inferiority relatively to vancomycin, particularly in the setting of recurrent and/or severe infection. After a CDI recurrence for the first time, fidaxomicin has been shown to be associated with lower likelihood of CDI recurrence compared to vancomycin. Fecal transplantation is now strongly recommended for multiple recurrent CDI and may have a role in refractory disease. Oral, frozen stool capsules may simplify fecal transplantation in the future, with preliminary promising results. Diverting loop ileostomy combined with colonic lavage is a potential alternative to colectomy in severe complicated CDI. Potential alternative therapies requiring further investigation include toxin-binding resins and immunotherapy.}, }
@article {pmid27774199, year = {2015}, author = {Sachs, RE and Edelstein, CA}, title = {Ensuring the safe and effective FDA regulation of fecal microbiota transplantation.}, journal = {Journal of law and the biosciences}, volume = {2}, number = {2}, pages = {396-415}, doi = {10.1093/jlb/lsv032}, pmid = {27774199}, issn = {2053-9711}, support = {I01 BX002660/BX/BLRD VA/United States ; }, abstract = {Scientists, policymakers, and medical professionals alike have become increasingly worried about the rise of antibiotic resistance, and the growing number of infections due to bacteria like Clostridium difficile, which cause a significant number of deaths and are imposing increasing costs on our health care system. However, in the last few years, fecal microbiota transplantation (FMT), the transplantation of stool from a healthy donor into the bowel of a patient, has emerged as a startlingly effective means to treat recurrent C. difficile infections. At present, the FDA is proposing to regulate FMT as a biologic drug. However, this proposed classification is both underregulatory and overregulatory. The FDA's primary goal is to ensure that patients have access to safe, effective treatments-and as such they should regulate some aspects of FMT more stringently than they propose to, and others less so. This essay will examine the nature of the regulatory challenges the FDA will face in deciding to regulate FMT as a biologic drug, and will then evaluate available policy alternatives for the FDA to pursue, ultimately concluding that the FDA ought to consider adopting a hybrid regulatory model as it has done in the case of cord blood.}, }
@article {pmid27344870, year = {2015}, author = {Bartnicka, A and Szachta, P and Gałecka, M}, title = {Faecal microbiota transplant - prospects and safety.}, journal = {Pomeranian journal of life sciences}, volume = {61}, number = {3}, pages = {282-286}, pmid = {27344870}, issn = {2450-4637}, mesh = {Clostridioides difficile/*physiology ; Clostridium Infections/*therapy ; Drug-Related Side Effects and Adverse Reactions ; Fecal Microbiota Transplantation/*standards ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; *Practice Guidelines as Topic ; }, abstract = {The intestinal microbiota, either directly or indirectly, plays an important role in maintaining the homeostasis of the body. The intestine microorganisms are significant due to the role they play in stimulating the development of the immune system, protecting against pathogens, and also managing metabolic and nutrient processing. The effectiveness of probiotics and prebiotics in various gastrointestinal diseases has been repeatedly confirmed. However, increasing interest in faecal transplantation has also been observed. Its efficacy in the treatment of pseudomembranous colitis has been repeatedly demonstrated. More often this method is discussed regarding the possibility of using it in other diseases linked with dysbiosis. Faecal microbiota transplantation, because of its rapid efficacy, minimal risk and adverse effects, relatively low cost, and the ability to re-establish the correct intestinal microbiota profile, could be an alternative treatment method in several other diseases. This paper will introduce the latest therapeutic aspects of microbiota transplantation, including its implications in the treatment of gastrointestinal diseases.}, }
@article {pmid27099570, year = {2015}, author = {Jung Lee, W and Lattimer, LD and Stephen, S and Borum, ML and Doman, DB}, title = {Fecal Microbiota Transplantation: A Review of Emerging Indications Beyond Relapsing Clostridium difficile Toxin Colitis.}, journal = {Gastroenterology &amp; hepatology}, volume = {11}, number = {1}, pages = {24-32}, pmid = {27099570}, issn = {1554-7914}, abstract = {The symbiotic relationship between gut microbiota and humans has been forged over many millennia. This relationship has evolved to establish an intimate partnership that we are only beginning to understand. Gut microbiota were once considered pathogenic, but the concept of gut microbiota and their influence in human health is undergoing a major paradigm shift, as there is mounting evidence of their impact in the homeostasis of intestinal development, metabolic activities, and the immune system. The disruption of microbiota has been associated with many gastrointestinal and nongastrointestinal diseases, and the reconstitution of balanced microbiota has been postulated as a potential therapeutic strategy. Fecal microbiota transplantation (FMT), a unique method to reestablish a sustained balance in the disrupted microbiota of diseased intestine, has demonstrated great success in the treatment of recurrent Clostridium difficile infection and has gained increasing acceptance in clinical use. The possibility of dysfunctional micro-biota playing a causative role in other gastrointestinal and nongas-trointestinal diseases, therefore, has also been raised, and there are an increasing number of studies supporting this hypothesis. FMT is emerging as a feasible therapeutic option for several diseases; however, its efficacy remains in question, given the lack of clinical trial data. Altering microbiota with FMT holds great promise, but much research is needed to further define FMT's therapeutic role and optimize the microbiota delivery system.}, }
@article {pmid27099569, year = {2015}, author = {Lichtenstein, GR}, title = {Fecal Microbiota Transplantation.}, journal = {Gastroenterology &amp; hepatology}, volume = {11}, number = {1}, pages = {12}, pmid = {27099569}, issn = {1554-7914}, }
@article {pmid27025632, year = {2015}, author = {Vincent, Y and Manji, A and Gregory-Miller, K and Lee, C}, title = {A Review of Management of Clostridium difficile Infection: Primary and Recurrence.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {4}, number = {4}, pages = {411-423}, pmid = {27025632}, issn = {2079-6382}, abstract = {Clostridium difficile infection (CDI) is a potentially fatal illness, especially in the elderly and hospitalized individuals. The recurrence and rates of CDI are increasing. In addition, some cases of CDI are refractory to the currently available antibiotics. The search for improved modalities for the management of primary and recurrent CDI is underway. This review discusses the current antibiotics, fecal microbiota transplantation (FMT) and other options such as immunotherapy and administration of non-toxigenic Clostridium difficile (CD) for the management of both primary and recurrent CDI.}, }
@article {pmid27025624, year = {2015}, author = {Borody, TJ and Peattie, D and Mitchell, SW}, title = {Fecal Microbiota Transplantation: Expanding Horizons for Clostridium difficile Infections and Beyond.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {4}, number = {3}, pages = {254-266}, pmid = {27025624}, issn = {2079-6382}, abstract = {Fecal Microbiota Transplantation (FMT) methodology has been progressively refined over the past several years. The procedure has an extensive track record of success curing Clostridium difficile infection (CDI) with remarkably few adverse effects. It achieves similar levels of success whether the CDI occurs in the young or elderly, previously normal or profoundly ill patients, or those with CDI in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we learned that using the procedure in other gastrointestinal (GI) diseases, such as IBD without CDI, generally fails to effect cure. To improve results in treating other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs) will be required to address questions about mechanisms operating within particular diseases. Availability of orally deliverable FMT products, such as capsules containing lyophilised fecal microbiota, will simplify CDI treatment and open the door to convenient, prolonged FMT delivery to the GI tract and will likely deliver improved results in both CDI and non-CDI diseases.}, }
@article {pmid27025623, year = {2015}, author = {Vincent, C and Manges, AR}, title = {Antimicrobial Use, Human Gut Microbiota and Clostridium difficile Colonization and Infection.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {4}, number = {3}, pages = {230-253}, pmid = {27025623}, issn = {2079-6382}, abstract = {Clostridium difficile infection (CDI) is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gut microbiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT) is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material.}, }
@article {pmid27019915, year = {2015}, author = {Małopolska, M and Fol, M}, title = {[Intestinal microbiota transplantation for the treatment of Clostridium difficile infection].}, journal = {Medycyna doswiadczalna i mikrobiologia}, volume = {67}, number = {3-4}, pages = {207-219}, pmid = {27019915}, issn = {0025-8601}, mesh = {*Clostridioides difficile ; Diarrhea/microbiology/*therapy ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Humans ; }, abstract = {The infections caused by C. difficile, responsible for the antibiotic-associated diarrhea and pseudomembranous colitis, are the growing health problem. An increasing number of C. difficile infection (CDI) cases and the phenomenon of multidrug-resistance of bacteria forces to find new, effective therapeutic methods. Intestinal microbiota transplantation ("fecal bacteriotherapy") is a promising remedy for patients suffering from recurrent, severe, not susceptible to standard treatments intestinal infection caused by C. difficile. Low cost, easy implementation and high efficiency at a short time treatment cause that it is a method increasingly tested and practiced by physicians. However, it is required to standardize the treatment procedure, as well as better understanding the biological mechanisms on which the treatment is based on.}, }
@article {pmid27356369, year = {2014}, author = {Debré, P and Le Gall, JY and , }, title = {[Intestinal microbiota].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {198}, number = {9}, pages = {1667-1684}, pmid = {27356369}, issn = {0001-4079}, mesh = {Colorectal Neoplasms/microbiology ; *Gastrointestinal Microbiome/physiology ; Humans ; Liver Neoplasms/microbiology ; Obesity/microbiology ; }, abstract = {The human body normally lives in symbiosis with a considerable microscopic environment present on all interfaces with the external environment; it hosts ten times more microbes (microbiota) that it has somatic or germ cells, representing a gene diversity (microbiome) 100-150 times higher than the human genome. These germs are located mainly in the gut, where they represent a mass of about one kilogram. The primary colonization of the gastrointestinal tract depends on the delivery route, the bacterial flora rewarding then depending on the environment, food hygiene, medical treatments. The intestinal microbiota plays an important role in the maturation of the immune system and in different physiological functions: digestion of polysaccharides, glycosaminoglycans and glycoproteins, vitamins biosynthesis, bile salt metabolism of some amino acids and xenobiotics. Quantitative and qualitative changes in the microbiota are observed in a wide range of diseases: obesity, colorectal cancer, liver cancer, inflammatory bowel disease, autoimmune diseases, allergies... pharmacobiotics aim to modify the intestinal microbiota in a therapeutic goal and this by various means: prebiotics, probiotics, antibiotics or fecal transplants. Intestinal flora also plays a direct role in the metabolism of certain drugs and the microbiota should be considered as a predictive parameter of response to some chemotherapies.}, }
@article {pmid27202489, year = {2014}, author = {Zowall, H and Brewer, C and Deutsch, A}, title = {Cost-Effectiveness of Fecal Microbiota Transplant in Treating Clostridium Difficile Infection in Canada.}, journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research}, volume = {17}, number = {7}, pages = {A676}, doi = {10.1016/j.jval.2014.08.2512}, pmid = {27202489}, issn = {1524-4733}, }
@article {pmid27400568, year = {2014}, author = {García, MD}, title = {[IRRITABLE BOWEL SYNDROME. NEW HORIZONS].}, journal = {Anales de la Real Academia Nacional de Medicina}, volume = {131}, number = {2}, pages = {479-492}, pmid = {27400568}, issn = {0034-0634}, mesh = {Dysbiosis ; Humans ; *Irritable Bowel Syndrome/microbiology/therapy ; Microbiota ; }, abstract = {Irritable bowel syndrome is a chronic disorder of complex genesis. Infections, indiscriminate use of antibiotics and bowel cleansing may affect the composition of the microbiota. Knowledge of host-microbiota interaction is important to deepen their pathogenesis and allow therapeutic modulation of the microbiota. The interaction between the microbiota, the immune system and the enteric nervous system is not yet well understood, but could be important in the pathophysiology of the disorder. New therapeutic possibilities found with prebiotics, probiotics, new painkillers and antibiotics such as rifaximin. The modification of the fecal microbiota by transplantation may become a future therapeutic option.}, }
@article {pmid27119092, year = {2014}, author = {Autio, K and Knuuttila, A and Kipar, A and Pesonen, S and Guse, K and Parviainen, S and Rajamäki, M and Laitinen-Vapaavuori, O and Vähä-Koskela, M and Kanerva, A and Hemminki, A}, title = {Safety and biodistribution of a double-deleted oncolytic vaccinia virus encoding CD40 ligand in laboratory Beagles.}, journal = {Molecular therapy oncolytics}, volume = {1}, number = {}, pages = {14002}, pmid = {27119092}, issn = {2372-7705}, abstract = {We evaluated adverse events, biodistribution and shedding of oncolytic vaccinia virus encoding CD40 ligand in two Beagles, in preparation for a phase 1 trial in canine cancer patients. Dog 1 received one dose of vaccinia virus and was euthanized 24 hours afterwards, while dog 2 received virus four times once weekly and was euthanized 7 days after that. Dogs were monitored for adverse events and underwent a detailed postmortem examination. Blood, saliva, urine, feces, and organs were collected for virus detection. Dog 1 had mild fever and lethargy while dog 2 experienced a possible seizure 5.5 hours after first virus administration. Viral DNA declined quickly in the blood after virus administration in both dogs but was still detectable 1 week later by quantitative polymerase chain reaction. Only samples taken directly after virus infusion contained infectious virus. Small amounts of viral DNA, but no infectious virus, were detected in a few saliva and urine samples. Necropsies did not reveal any relevant pathological changes and virus DNA was detected mainly in the spleen. The dogs in the study did not have cancer, and thus adverse events could be more common and viral load higher in dogs with tumors which allow viral amplification.}, }
@article {pmid28466211, year = {2002}, author = {Takada, M and Asada, M and Miyashita, T}, title = {Cross-habitat foraging by sika deer influences plant community structure in a forest-grassland landscape.}, journal = {Oecologia}, volume = {133}, number = {3}, pages = {389-394}, doi = {10.1007/s00442-002-1037-y}, pmid = {28466211}, issn = {1432-1939}, abstract = {We demonstrated the effect of cross-habitat foraging by sika deer (Cervus nippon) on plant communities under the hypothesis that the intensity of herbivory on a plant community is changed by the presence of a preferable habitat for deer nearby. To investigate this landscape-level effect, we examined two types of forest understory; "adjacent site" was located near agricultural fields where deer prefer to forage, and "remote site" was far from fields. We compared plant community structures between adjacent and remote sites in areas with high deer densities, and found that plant species richness and plant coverage were significantly higher in adjacent sites than in remote sites. We hypothesized that this difference was caused by the lower intensity of browsing at adjacent sites due to the higher use of fields by the deer at these sites. The following four results supported this hypothesis. First, in areas with no deer, plant species richness and plant coverage did not differ significantly between adjacent and remote sites. Second, we demonstrated a lower intensity of herbivory at adjacent sites by experimentally transplanting a preferred plant species, Aucuba japonica. Third, we detected no difference in the number of deer fecal pellets found in adjacent and remote sites, indicating that the difference in browsing intensity between the two sites was not due to differences in the frequency of site use by the deer. Fourth, fecal analysis showed that deer at adjacent sites consumed more graminoids, suggesting that deer at these sites used fields to forage because graminoids were abundant in fields. All of these results support the notion that the intensity of herbivory on forest understorys becomes lower in the presence of agricultural fields nearby. This also implies the importance of the indirect effects at the landscape level in that the two ecosystems are linked by the consumers moving between them.}, }
@article {pmid27265592, year = {1999}, author = {Yalçın, A and Avcu, F and Ural, AU and Beyan, C and Omay, SB and Tanyüksel, M and Doğancı, L}, title = {Schistosoma mansoni Infection Following Allogeneic Bone Marrow Transplantation.}, journal = {Turkish journal of haematology : official journal of Turkish Society of Haematology}, volume = {16}, number = {4}, pages = {181-184}, pmid = {27265592}, issn = {1300-7777}, abstract = {A case of Schistosoma mansoni infection in a 28 year old male after allogeneic bone marrow transplantation presenting with portal hypertension and gross hematuria is described. Schistosomiasis was confirmed by the discovery of parasites in the feces, together with the failure the patient to respond to multiple antimicrobial and antifungal treatment. After praziquantel administration, toxic or septic shock syndrome evolved and the patients died of acute renal failure on day 39 post-transplant. In this report, we would like to emphasize the importance of pre-transplant stool and urine cultures, and appropriate serologic tests in patients coming from endemic areas. Patients diagnosed with schistosomiasis must be treated at least 3 to 7 weeks before transplantation.}, }
@article {pmid26687459, year = {2015}, author = {Su, X and Yan, H and Huang, Y and Yun, H and Zeng, B and Wang, E and Liu, Y and Zhang, Y and Liu, F and Che, Y and Zhang, Z and Yang, R}, title = {Expression of FABP4, adipsin and adiponectin in Paneth cells is modulated by gut Lactobacillus.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {18588}, pmid = {26687459}, issn = {2045-2322}, mesh = {Adiponectin/*biosynthesis/genetics ; Animals ; Complement Factor D/*biosynthesis/genetics ; Fatty Acid-Binding Proteins/*biosynthesis/genetics ; Feces ; Gastrointestinal Microbiome/*genetics ; Gene Expression Regulation/genetics ; Humans ; Lactobacillus/*metabolism ; Mice ; NF-kappa B/biosynthesis ; Paneth Cells/metabolism/pathology ; TNF Receptor-Associated Factor 2/genetics ; TNF Receptor-Associated Factor 6/genetics ; }, abstract = {We here found that intestinal epithelial Paneth cells secrete FABP4, adipsin and adiponectin in both mice and human. Deletion of Paneth cell results in the decrease of FABP4, adipsin and adiponectin not only in intestinal crypt cells but also in sera, suggesting that they may influence the state of the whole body. We also demonstrate that expression of FABP4, adipsin and adiponectin may be modulated by specific gut microbiota. In germ-free (GF) mice, the expression of FABP4, adipsin and adiponectin were lower or difficult to be detected. Feces transplantation promoted the expression of FABP4, adipsin and adiponectin in gut epithelial Paneth cells. We have found that Lactobacillus NK6 colony, which has the highest similarity with Lactobacillus taiwanensis strain BCRC 17755, may induce the expression of FABP4, adipsin and adiponectin through TRAF2 and TRAF6 ubiquitination mediated NF-κB signaling. Taken together, our findings set up a novel mechanism for FABP4, adipsin and adiponectin through gut microbiota mediating expression in gut Paneth cells.}, }
@article {pmid26682948, year = {2016}, author = {Kuethe, JW and Armocida, SM and Midura, EF and Rice, TC and Hildeman, DA and Healy, DP and Caldwell, CC}, title = {Fecal Microbiota Transplant Restores Mucosal Integrity in a Murine Model of Burn Injury.}, journal = {Shock (Augusta, Ga.)}, volume = {45}, number = {6}, pages = {647-652}, pmid = {26682948}, issn = {1540-0514}, support = {T32 GM008478/GM/NIGMS NIH HHS/United States ; T35 DK060444/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Burns/*microbiology/pathology/therapy ; Colon/*microbiology ; Disease Models, Animal ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Intestines/microbiology ; Mice ; Microbiota ; Permeability ; }, abstract = {The gut microbiome is a community of commensal organisms that are known to play a role in nutrient production as well as gut homeostasis. The composition of the gut flora can be affected by many factors; however, the impact of burn injury on the microbiome is not fully known. Here, we hypothesized that burn-induced changes to the microbiome would impact overall colon health. After scald-burn injury, cecal samples were analyzed for aerobic and anaerobic colony forming units, bacterial community, and butyrate levels. In addition, colon and total intestinal permeabilities were determined. These parameters were further determined in a germ-reduced murine model. Following both burn injury and germ reduction, we observed decreases in aerobic and anaerobic bacteria, increased colon permeability and no change to small intestinal permeability. After burn injury, we further observed a significant decrease in the butyrate producing bacteria R. Gnavus, C. Eutactus, and Roseburia species as well as decreases in colonic butyrate. Finally, in mice that underwent burn followed by fecal microbiota transplant, bacteria levels and mucosal integrity were restored. Altogether our data demonstrate that burn injury can alter the microbiome leading to decreased butyrate levels and increased colon permeability. Of interest, fecal microbiota transplant treatment was able to ameliorate the burn-induced changes in colon permeability. Thus, fecal transplantation may represent a novel therapy in restoring colon health after burn injury.}, }
@article {pmid26678555, year = {2016}, author = {Verbeken, G and Huys, I and De Vos, D and De Coninck, A and Roseeuw, D and Kets, E and Vanderkelen, A and Draye, JP and Rose, T and Jennes, S and Ceulemans, C and Pirnay, JP}, title = {Access to bacteriophage therapy: discouraging experiences from the human cell and tissue legal framework.}, journal = {FEMS microbiology letters}, volume = {363}, number = {4}, pages = {}, doi = {10.1093/femsle/fnv241}, pmid = {26678555}, issn = {1574-6968}, mesh = {Bacterial Infections/microbiology/*therapy ; *Bacteriophages/growth &amp; development/isolation &amp; purification ; Biological Therapy/history/*standards ; Europe ; Fecal Microbiota Transplantation ; Government Regulation/history ; History, 20th Century ; Humans ; Keratinocytes ; }, abstract = {Cultures of human epithelial cells (keratinocytes) are used as an additional surgical tool to treat critically burnt patients. Initially, the production environment of keratinocyte grafts was regulated exclusively by national regulations. In 2004, the European Tissues and Cells Directive 2004/23/EC (transposed into Belgian Law) imposed requirements that resulted in increased production costs and no significant increase in quality and/or safety. In 2007, Europe published Regulation (EC) No. 1394/2007 on Advanced Therapy Medicinal Products. Overnight, cultured keratinocytes became (arguably) 'Advanced' Therapy Medicinal Products to be produced as human medicinal products. The practical impact of these amendments was (and still is) considerable. A similar development appears imminent in bacteriophage therapy. Bacteriophages are bacterial viruses that can be used for tackling the problem of bacterial resistance development to antibiotics. Therapeutic natural bacteriophages have been in clinical use for almost 100 years. Regulators today are framing the (re-)introduction of (natural) bacteriophage therapy into 'modern western' medicine as biological medicinal products, also subject to stringent regulatory medicinal products requirements. In this paper, we look back on a century of bacteriophage therapy to make the case that therapeutic natural bacteriophages should not be classified under the medicinal product regulatory frames as they exist today. It is our call to authorities to not repeat the mistake of the past.}, }
@article {pmid26675010, year = {2015}, author = {Kazerouni, A and Burgess, J and Burns, LJ and Wein, LM}, title = {Optimal screening and donor management in a public stool bank.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {75}, pmid = {26675010}, issn = {2049-2618}, mesh = {Biological Specimen Banks/*standards ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/therapy ; Disease Management ; Donor Selection/economics/*methods ; *Fecal Microbiota Transplantation/standards ; Feces/*microbiology/virology ; Humans ; Models, Statistical ; Rotavirus/isolation &amp; purification ; }, abstract = {BACKGROUND: Fecal microbiota transplantation is an effective treatment for recurrent Clostridium difficile infection and is being investigated as a treatment for other microbiota-associated diseases. To facilitate these activities, an international public stool bank has been created, which screens donors and processes stools in a standardized manner. The goal of this research is to use mathematical modeling and analysis to optimize screening and donor management at the stool bank.<br><br>RESULTS: Compared to the current policy of screening active donors every 60 days before releasing their quarantined stools for sale, costs can be reduced by 10.3 % by increasing the screening frequency to every 36 days. In addition, the stool production rate varies widely across donors, and using donor-specific screening, where higher producers are screened more frequently, also reduces costs, as does introducing an interim (i.e., between consecutive regular tests) stool test for just rotavirus and C. difficile. We also derive a donor release (i.e., into the system) policy that allows the supply to approximately match an exponentially increasing deterministic demand.<br><br>CONCLUSIONS: More frequent screening, interim screening for rotavirus and C. difficile, and donor-specific screening, where higher stool producers are screened more frequently, are all cost-reducing measures. If screening costs decrease in the future (e.g., as a result of bringing screening in house), a bottleneck for implementing some of these recommendations may be the reluctance of donors to undergo serum screening more frequently than monthly.}, }
@article {pmid26673501, year = {2015}, author = {Jia, N}, title = {A Misleading Reference for Fecal Microbiota Transplant.}, journal = {The American journal of gastroenterology}, volume = {110}, number = {12}, pages = {1731}, pmid = {26673501}, issn = {1572-0241}, mesh = {*Clostridioides difficile ; *Colonoscopy ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; }, }
@article {pmid26662643, year = {2016}, author = {Li, YT and Cai, HF and Wang, ZH and Xu, J and Fang, JY}, title = {Systematic review with meta-analysis: long-term outcomes of faecal microbiota transplantation for Clostridium difficile infection.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {43}, number = {4}, pages = {445-457}, doi = {10.1111/apt.13492}, pmid = {26662643}, issn = {1365-2036}, mesh = {Age Factors ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces ; Humans ; Observational Studies as Topic ; Recurrence ; Risk Factors ; }, abstract = {BACKGROUND: Clostridium difficile infection is a major cause of nosocomial diarrhoea.<br><br>AIM: To evaluate long-term (&#x2265;90 days) efficacy and safety of faecal microbiota transplantation for C. difficile infection and explore the factors affecting the faecal microbiota transplantation outcomes.<br><br>METHODS: MEDLINE, the Cochrane Library and EMBASE were searched and only observational studies that utilised faecal microbiota transplantation for C. difficile infection with long-term follow-up duration (&#x2265;90 days) were included. Primary cure rate, overall recurrence rate and early (<90 days) and late (&#x2265;90 days) recurrence rate were calculated.<br><br>RESULTS: Eighteen observational studies with 611 patients were included. The primary cure rate was 91.2% (95% confidence interval, CI 86.7-94.8%). The overall recurrence rate was 5.5% (95% CI 2.2-10.3%). The early recurrence rate and late recurrence rate were 2.7% (95% CI 0.7-6.0%) and 1.7% (95% CI 0.4-4.2%) respectively. Most adverse events were expected, short-lived, self-limited and manageable. The association between faecal microbiota transplantation therapy and adverse events such as inflammatory bowel disease flare, infectious disease and autoimmune disease was a concern but remained insignificant. Old age (&#x2265;65 years) was identified as a risk factor for after faecal microbiota transplantation therapy. Upper gastrointestinal administration also results in less frequent primary cure.<br><br>CONCLUSIONS: Faecal microbiota transplantation seems to be a highly effective and robust therapy for recurrent C. difficile infection. However, more quality studies, such as randomised controlled trials and cohort studies with control groups, are needed to confirm its long-term efficacy and safety.}, }
@article {pmid26654550, year = {2016}, author = {Sebastián Domingo, JJ}, title = {[Irritable bowel syndrome: the next-to-last that is being investigated].}, journal = {Medicina clinica}, volume = {146}, number = {6}, pages = {260-262}, doi = {10.1016/j.medcli.2015.10.010}, pmid = {26654550}, issn = {1578-8989}, mesh = {Antidepressive Agents, Tricyclic/therapeutic use ; Biomarkers ; Complementary Therapies ; Diet/adverse effects ; Dietary Carbohydrates/adverse effects ; Fecal Microbiota Transplantation ; Fermentation ; Humans ; *Irritable Bowel Syndrome/etiology/immunology/metabolism/therapy ; Melatonin/therapeutic use ; Peptides/therapeutic use ; Probiotics/therapeutic use ; }, }
@article {pmid26651511, year = {2015}, author = {Perkel, J}, title = {THE BACTERIA AMONG US.}, journal = {BioTechniques}, volume = {59}, number = {6}, pages = {324-6, 328}, doi = {10.2144/000114360}, pmid = {26651511}, issn = {1940-9818}, mesh = {Fecal Microbiota Transplantation ; Humans ; Microbiology/*trends ; *Microbiota ; Neoplasms/microbiology ; }, abstract = {A growing number of studies are linking microbes in our bodies with physiology and disease. Jeffrey Perkel speaks to researchers trying to understand this relationship and, possibly, even use it to improve human health.}, }
@article {pmid26645757, year = {2015}, author = {Eliadou, E and Day, AS and Thompson-Fawcett, MW and Gearry, RB and Rowbotham, DS and Walmsley, R and Schultz, M and Inns, SJ and ,  and , }, title = {New Zealand Society of Gastroenterology Guidelines for the Management of Refractory Ulcerative Colitis.}, journal = {The New Zealand medical journal}, volume = {128}, number = {1423}, pages = {63-76}, pmid = {26645757}, issn = {1175-8716}, mesh = {Adalimumab/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Appendectomy ; Azathioprine/therapeutic use ; Colitis, Ulcerative/*therapy ; Cyclosporine/therapeutic use ; Drug Resistance ; Drug Therapy, Combination ; Fecal Microbiota Transplantation ; Gastrointestinal Agents/therapeutic use ; Humans ; Immunosuppressive Agents/therapeutic use ; Infliximab/therapeutic use ; Leukapheresis ; Mercaptopurine/therapeutic use ; Mesalamine/therapeutic use ; Methotrexate/therapeutic use ; New Zealand ; Pediatrics ; Piperidines/therapeutic use ; Proctocolectomy, Restorative ; Protein Kinase Inhibitors/therapeutic use ; Pyrimidines/therapeutic use ; Pyrroles/therapeutic use ; Recurrence ; Severity of Illness Index ; Tacrolimus/therapeutic use ; Tumor Necrosis Factor-alpha/antagonists &amp; inhibitors ; }, abstract = {The management of patients with ulcerative colitis who are dependent on corticosteroid for control of symptoms, or refractory to corticosteroids or standard immunosuppressive therapy, is challenging. The development of newer medical therapies has increased the options for managing patients in this situation, but access and funding remain limited. This guideline summarises the literature regarding this situation and provides guidance as to the management of refractory colitis in the New Zealand setting.}, }
@article {pmid26643655, year = {2016}, author = {Padua, D and Pothoulakis, C}, title = {Novel approaches to treating Clostridium difficile-associated colitis.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {10}, number = {2}, pages = {193-204}, pmid = {26643655}, issn = {1747-4132}, support = {T32 DK007180/DK/NIDDK NIH HHS/United States ; 1P50 DK64539/DK/NIDDK NIH HHS/United States ; R01 DK047343/DK/NIDDK NIH HHS/United States ; R01 DK060729/DK/NIDDK NIH HHS/United States ; P30 DK041301/DK/NIDDK NIH HHS/United States ; P50 DK064539/DK/NIDDK NIH HHS/United States ; T32 DK07180-40/DK/NIDDK NIH HHS/United States ; P30 DK 41301/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Bacterial Vaccines/adverse effects/*therapeutic use ; Clostridioides difficile/immunology/*pathogenicity ; Clostridium Infections/diagnosis/microbiology/*therapy ; Colitis/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Probiotics/adverse effects/*therapeutic use ; Treatment Outcome ; }, abstract = {Clostridium difficile is being recognized as a growing threat to many health-care systems. Epidemiology data shows that infection rates are soaring and the disease burden is increasing. Despite the efficacy of standard treatments, it is becoming evident that novel therapeutics will be required to tackle this disease. These new treatments aim to enhance the intestinal microbial barrier, activate the immune system and neutralize the toxins that mediate this disease. Many of these therapies are still in the beginning stages of investigation, however, in the next few years, more clinical data will become available to help implement many of these exciting new therapeutic approaches.}, }
@article {pmid26641310, year = {2016}, author = {Lübbert, C}, title = {Antimicrobial therapy of acute diarrhoea: a clinical review.}, journal = {Expert review of anti-infective therapy}, volume = {14}, number = {2}, pages = {193-206}, doi = {10.1586/14787210.2016.1128824}, pmid = {26641310}, issn = {1744-8336}, mesh = {Acute Disease ; Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Azithromycin/therapeutic use ; Bacterial Infections/diagnosis/*drug therapy ; Campylobacter Infections/diagnosis/drug therapy ; Cholera/diagnosis/drug therapy ; Ciprofloxacin/therapeutic use ; Diarrhea/*drug therapy ; Dysbiosis/chemically induced ; Dysentery, Bacillary/diagnosis/drug therapy ; Enterocolitis, Pseudomembranous/diagnosis/drug therapy ; Escherichia coli Infections/diagnosis/drug therapy ; Fidaxomicin ; Gastroenteritis/*drug therapy ; Humans ; Rifamycins/therapeutic use ; Rifaximin ; Salmonella Infections/diagnosis/drug therapy ; Shiga-Toxigenic Escherichia coli ; Yersinia Infections/diagnosis/drug therapy ; }, abstract = {Diarrhoea is one of the most commonly occurring diseases. This article presents a review of the current state of the treatment of acute infectious diarrhoea, as well as of the most important pathogens. The general principles of the therapy of diarrhoea are exemplified, followed by a description of the targeted antimicrobial therapy of the most important bacterial gastrointestinal infections, including salmonellosis, shigellosis and Campylobacter infections, as well as infections with pathogenic Escherichia coli strains, yersiniosis and cholera. Diarrhoea caused by toxigenic Clostridium difficile strains has increased in incidence and in severity. These infections will therefore be described in detail, including important new aspects of treatment. Symptomatic therapy is still the most important component of the treatment of infectious diarrhoea. However, empirical antibiotic therapy should be considered for severely ill patients with a high frequency of stools, fever, bloody diarrhoea, underlying immune deficiency, advanced age or significant comorbidities. Increasing resistance, in particular against fluoroquinolones, must be taken into consideration. Therapy with motility inhibitors is not recommended for Shiga toxin-producing Escherichia coli (STEC) infections, Clostridium difficile infections (CDI), and severe colitis. The macrocyclic antibiotic fidaxomicin can reduce the rate of recurrent disease in CDI. Furthermore, evidence for the benefits of faecal microbiota transplantation as a treatment option for multiple recurrences of CDI is increasing. In conclusion, the treatment of acute diarrhoea is still primarily supportive. General empirical antibiotic therapy for acute diarrhoea is not evidence-based.}, }
@article {pmid26628567, year = {2016}, author = {Costello, SP and Tucker, EC and La Brooy, J and Schoeman, MN and Andrews, JM}, title = {Establishing a Fecal Microbiota Transplant Service for the Treatment of Clostridium difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {62}, number = {7}, pages = {908-914}, doi = {10.1093/cid/civ994}, pmid = {26628567}, issn = {1537-6591}, mesh = {Adult ; *Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation/methods/standards ; Feces/microbiology/parasitology/virology ; Humans ; Middle Aged ; *Tissue Banks ; *Tissue Donors ; Young Adult ; }, abstract = {Recurrent or refractory Clostridium difficile infection (CDI) has become an increasing problem in the past decade. Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent CDI; however, a number of technical, logistical, and regulatory issues have hampered the development of an FMT capability at many hospitals. The development of a frozen stool bank of screened donor stool is an important step in the standardization of the procedure. This gives clinicians rapid access to thoroughly screened donor stool when needed, without the ethical and logistical problems associated with patient-selected donors. We describe the practicalities of establishing such a service using a stool bank of prescreened donor stool including detail regarding donor recruitment and screening, stool preparation, and delivery of the FMT.}, }
@article {pmid26621029, year = {2016}, author = {Ratto, C and Buntzen, S and Aigner, F and Altomare, DF and Heydari, A and Donisi, L and Lundby, L and Parello, A}, title = {Multicentre observational study of the Gatekeeper for faecal incontinence.}, journal = {The British journal of surgery}, volume = {103}, number = {3}, pages = {290-299}, pmid = {26621029}, issn = {1365-2168}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anal Canal/physiopathology/*surgery ; Defecation/*physiology ; Feasibility Studies ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; *Prostheses and Implants ; Prosthesis Design ; Prosthesis Implantation/*methods ; *Quality of Life ; Treatment Outcome ; }, abstract = {BACKGROUND: A variety of therapeutic approaches are available for faecal incontinence. Implantation of Gatekeeper prostheses is a new promising option. The primary endpoint of this prospective observational multicentre study was to assess the clinical efficacy of Gatekeeper implantation in patients with faecal incontinence. Secondary endpoints included the assessment of patients' quality of life, and the feasibility and safety of implantation.<br><br>METHODS: Patients with faecal incontinence, with either intact sphincters or internal anal sphincter lesions extending for less than 60&#xb0; of the anal circumference, were selected. Intersphincteric implantation of six prostheses was performed. At baseline, and 1, 3 and 12 months after implantation, the number of faecal incontinence episodes, Cleveland Clinic Faecal Incontinence, Vaizey and American Medical Systems, Faecal Incontinence Quality of Life Scale and Short Form 36 Health Survey scores were recorded. Endoanal ultrasonography was performed at baseline and follow-up.<br><br>RESULTS: Fifty-four patients were implanted. After Gatekeeper implantation, incontinence to gas, liquid and solid stool improved significantly, soiling was reduced, and ability to defer defaecation enhanced. All faecal incontinence severity scores were significantly reduced, and patients' quality of life improved. At 12 months, 30 patients (56 per cent) showed at least 75 per cent improvement in all faecal incontinence parameters, and seven (13 per cent) became fully continent. In three patients a single prosthesis was extruded during surgery, but was replaced immediately. After implantation, prosthesis dislodgement occurred in three patients; no replacement was required.<br><br>CONCLUSION: Anal implantation of the Gatekeeper in patients with faecal incontinence was effective and safe. Clinical benefits were sustained at 1-year follow-up.}, }
@article {pmid26616573, year = {2016}, author = {Cui, B and Xu, F and Zhang, F}, title = {Methodology, Not Concept of Fecal Microbiota Transplantation, Affects Clinical Findings.}, journal = {Gastroenterology}, volume = {150}, number = {1}, pages = {285-286}, doi = {10.1053/j.gastro.2015.05.065}, pmid = {26616573}, issn = {1528-0012}, mesh = {Biological Therapy/*methods ; Colitis, Ulcerative/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; }, }
@article {pmid26616138, year = {2017}, author = {Davidovics, ZH and Vance, K and Etienne, N and Hyams, JS}, title = {Fecal Transplantation Successfully Treats Recurrent D-Lactic Acidosis in a Child With Short Bowel Syndrome.}, journal = {JPEN. Journal of parenteral and enteral nutrition}, volume = {41}, number = {5}, pages = {896-897}, doi = {10.1177/0148607115619931}, pmid = {26616138}, issn = {1941-2444}, mesh = {Acidosis, Lactic/complications/*therapy ; Adolescent ; *Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Humans ; Intestinal Mucosa/metabolism ; Intestines/microbiology ; Lactic Acid/blood ; Male ; Recurrence ; Short Bowel Syndrome/complications/*therapy ; }, abstract = {D-lactic acidosis can occur in patients with short bowel syndrome (SBS) when excessive malabsorbed carbohydrate (CHO) enters the colon and is metabolized by colonic bacteria to D-lactate. D-lactate can be absorbed systemically, and increased serum levels are associated with central nervous system toxicity manifested by confusion, ataxia, and slurred speech. Current therapy, usually directed toward suppressing intestinal bacterial overgrowth and limiting ingested CHO, is not always successful. Fecal transplantation, the infusion of donor feces into a recipient's intestinal tract, has been used for decades to treat recurrent Clostridium difficile infection, and case reports document its use in the successful treatment of constipation, diarrhea, and abdominal pain. The exact mechanism of action is unknown, but it is surmised that the alteration of the intestinal microbiome, as well as the reintroduction of potential beneficial microbes, helps mediate disease. Here we present the case of a child with SBS and recurrent, debilitating D-lactic acidosis, which was successfully treated with fecal transplantation.}, }
@article {pmid26612676, year = {2016}, author = {Henkenberens, C and Merseburger, AS and Bengel, F and Derlin, T and Hueper, K and Grünwald, V and Christiansen, H}, title = {Radiotherapy for isolated lymph node metastases in patients with locally advanced prostate cancer after primary therapy.}, journal = {World journal of urology}, volume = {34}, number = {9}, pages = {1239-1245}, pmid = {26612676}, issn = {1433-8726}, mesh = {Aged ; Aged, 80 and over ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Prostatic Neoplasms, Castration-Resistant/pathology/*radiotherapy ; Retrospective Studies ; }, abstract = {PURPOSE: To evaluate the outcome of radiotherapy for isolated lymph node metastases in patients with progression towards castration-resistant prostate cancer (CRPC) after definitive therapy.<br><br>METHODS: Between 11/2009 and 06/2014, 18 patients with isolated lymph node metastases after definitive prostate cancer therapy received radiotherapy to the affected lymph nodes with a total dose of 50.4 or 54.0&#xa0;Gray (Gy). All patients had continuously rising levels of PSA despite androgen deprivation therapy (ADT). Biochemical progression-free survival (BPFS), clinical failure-free survival (CFFS) and freedom from local failure were assessed, as was the toxicity profile.<br><br>RESULTS: Of the 18 patients, 17 had high-risk prostate cancer. Radiotherapy was performed at a median interval of 64.55 [interquartile range (IQR) 23.2-153.8] months after definitive therapy. ADT was administered for a median (IQR) time of 3.8 (3.2-24.7) months prior to irradiation. The median (IQR) follow-up was 15.59 (5.3-28.5) months with 94.1&#xa0;% freedom from local failure. The median BPFS and CFFS were 5.85 (IQR 3.0-20.3) and 9.60&#xa0;months (IQR 5.9-28.8), respectively. No grade III acute or grade II late toxicity was observed. Only two patients developed local relapse. No patients exhibited deterioration of urinary or faecal continence.<br><br>CONCLUSION: Radiotherapy of isolated lymph node metastases in patients who develop CRPC provides effective local control, is not associated with clinically important acute or long-term side effects, improves PSA kinetics and may delay the necessity of chemotherapy.}, }
@article {pmid26601705, year = {2016}, author = {Dantes, R and Epson, EE and Dominguez, SR and Dolan, S and Wang, F and Hurst, A and Parker, SK and Johnston, H and West, K and Anderson, L and Rasheed, JK and Moulton-Meissner, H and Noble-Wang, J and Limbago, B and Dowell, E and Hilden, JM and Guh, A and Pollack, LA and Gould, CV}, title = {Investigation of a cluster of Clostridium difficile infections in a pediatric oncology setting.}, journal = {American journal of infection control}, volume = {44}, number = {2}, pages = {138-145}, pmid = {26601705}, issn = {1527-3296}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Adolescent ; Anti-Bacterial Agents/*therapeutic use ; Case-Control Studies ; Cefepime ; Cephalosporins/*therapeutic use ; Child ; Child, Preschool ; Clostridioides difficile/classification/drug effects/*isolation &amp; purification ; Clostridium Infections/drug therapy/*epidemiology/microbiology ; Cross Infection/drug therapy/*epidemiology/microbiology ; Feces/microbiology ; Female ; Hospitalization ; Hospitals ; Humans ; Infant ; *Infection Control ; Male ; Medical Oncology ; Pediatrics ; Risk Factors ; Young Adult ; }, abstract = {BACKGROUND: We investigated an increase in Clostridium difficile infection (CDI) among pediatric oncology patients.<br><br>METHODS: CDI cases were defined as first C difficile positive stool tests between December 1, 2010, and September 6, 2012, in pediatric oncology patients receiving inpatient or outpatient care at a single hospital. A case-control study was performed to identify CDI risk factors, infection prevention and antimicrobial prescribing practices were assessed, and environmental sampling was conducted. Available isolates were strain-typed by pulsed-field gel electrophoresis.<br><br>RESULTS: An increase in hospital-onset CDI cases was observed from June-August 2012. Independent risk factors for CDI included hospitalization in the bone marrow transplant ward and exposure to computerized tomography scanning or cefepime in the prior 12&#xa0;weeks. Cefepime use increased beginning in late 2011, reflecting a practice change for patients with neutropenic fever. There were 13 distinct strain types among 22 available isolates. Hospital-onset CDI rates decreased to near-baseline levels with enhanced infection prevention measures, including environmental cleaning and prolonged contact isolation.<br><br>CONCLUSION: C difficile strain diversity associated with a cluster of CDI among pediatric oncology patients suggests a need for greater understanding of modes and sources of transmission and strategies to reduce patient susceptibility to CDI. Further research is needed on the risk of CDI with cefepime and its use as primary empirical treatment for neutropenic fever.}, }
@article {pmid26600975, year = {2015}, author = {Schenck, LP and Beck, PL and MacDonald, JA}, title = {Gastrointestinal dysbiosis and the use of fecal microbial transplantation in Clostridium difficile infection.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {6}, number = {4}, pages = {169-180}, pmid = {26600975}, issn = {2150-5330}, abstract = {The impact of antibiotics on the human gut microbiota is a significant concern. Antibiotic-associated diarrhea has been on the rise for the past few decades with the increasing usage of antibiotics. Clostridium difficile infections (CDI) have become one of the most prominent types of infectious diarrheal disease, with dramatically increased incidence in both the hospital and community setting worldwide. Studies show that variability in the innate host response may in part impact upon CDI severity in patients. That being said, CDI is a disease that shows the most prominent links to alterations to the gut microbiota, in both cause and treatment. With recurrence rates still relatively high, it is important to explore alternative therapies to CDI. Fecal microbiota transplantation (FMT) and other types of bacteriotherapy have become exciting avenues of treatment for CDI. Recent clinical trials have generated excitement for the use of FMT as a therapeutic option for CDI; however, the exact components of the human gut microbiota needed for protection against CDI have remained elusive. Additional investigations on the effects of antibiotics on the human gut microbiota and subsequent CDI will help reduce the socioeconomic burden of CDI and potentially lead to new therapeutic modalities.}, }
@article {pmid26598578, year = {2015}, author = {Scroggie, DL and Al-Whouhayb, M}, title = {Asymptomatic giant appendicolith managed conservatively.}, journal = {Journal of surgical case reports}, volume = {2015}, number = {11}, pages = {}, pmid = {26598578}, issn = {2042-8812}, abstract = {A 67-year-old lady was found to have a giant appendicolith during a colorectal cancer screening colonoscopy, following a positive faecal occult blood test. Computed tomography confirmed the presence of a calcified giant appendicolith within the base of the appendix, which otherwise appeared normal. Appendicoliths are widely believed to be a major cause of acute appendicitis via obstruction of the appendix lumen, although this is disputed due to a lack of strong evidence. They may also cause chronic abdominal pain. All of the few cases of giant appendicoliths reported so far have been managed by extracting the lesions. Our patient was asymptomatic and had bilateral lung transplants, so a conservative watchful waiting approach was adopted. The authors propose expectant management of giant appendicoliths as a reasonable option in patients with significant operative risks.}, }
@article {pmid26598094, year = {2015}, author = {Crow, JR and Davis, SL and Chaykosky, DM and Smith, TT and Smith, JM}, title = {Probiotics and Fecal Microbiota Transplant for Primary and Secondary Prevention of Clostridium difficile Infection.}, journal = {Pharmacotherapy}, volume = {35}, number = {11}, pages = {1016-1025}, doi = {10.1002/phar.1644}, pmid = {26598094}, issn = {1875-9114}, mesh = {Clostridioides difficile/*growth &amp; development ; Cross Infection/diet therapy/prevention &amp; control/*therapy ; Diarrhea/diet therapy/prevention &amp; control/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Practice Guidelines as Topic ; Primary Prevention/*methods ; Probiotics/*therapeutic use ; Recurrence ; Secondary Prevention/*methods ; }, abstract = {Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea and is associated with an increased risk of mortality. The use of probiotics and fecal microbiota transplantation (FMT) has been studied to reduce the incidence and severity of this infection, but variable efficacy and safety data have been reported. Probiotics are hypothesized to be effective in the management of CDI through a number of mechanisms that include maintenance of normal gastrointestinal flora, antimicrobial and antitoxin properties, and immunomodulatory effects. Despite promising results in small trials and meta-analyses, prospective, randomized, controlled trials have not demonstrated probiotics to be effective in the primary prevention of C. difficile-associated diarrhea (CDAD). Probiotics may be effective for secondary prevention in patients with recurrent CDI, but guidelines acknowledge the lack of compelling evidence. Trials are limited by the use of varying types of strains, numbers of strains, and doses of probiotics, as well the definitions of CDI and CDAD. FMT has been proposed as a method for restoring gut microbiota and has been shown to significantly increase the rate of cure in patients with recurrent CDI. Current studies have demonstrated minimal adverse effects, with no reports of transmission of infectious diseases; however, the optimal delivery method, sample preparation, and donor selection remain unclear. In this review, findings from recent literature are highlighted, and guideline recommendations for the use of these agents in the primary and secondary prevention of CDI are summarized.}, }
@article {pmid26594828, year = {2016}, author = {Morinville, V and Ahmed, N and Ibberson, C and Kovacs, L and Kaczorowski, J and Bryan, S and Collet, JP and Schreiber, R}, title = {Home-Based Screening for Biliary Atresia Using Infant Stool Color Cards in Canada: Quebec Feasibility Study.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {62}, number = {4}, pages = {536-541}, doi = {10.1097/MPG.0000000000001042}, pmid = {26594828}, issn = {1536-4801}, support = {HERU1/CSO_/Chief Scientist Office/United Kingdom ; 210874/CAPMC/CIHR/Canada ; }, mesh = {Biliary Atresia/*diagnosis ; Cohort Studies ; Color ; *Family ; Feasibility Studies ; Feces/*chemistry ; Female ; Health Knowledge, Attitudes, Practice ; Hospitals, Teaching ; Humans ; Infant, Newborn ; Male ; Neonatal Screening/*methods ; Patient Compliance ; Patient Education as Topic ; Postal Service ; Quebec ; *Self Care ; Self Report ; *Urban Health ; }, abstract = {OBJECTIVES: Biliary atresia (BA) is a leading cause of liver failure and liver transplantation in pediatrics. BA manifests by 3 weeks of life with jaundice and pale stools. Delayed diagnosis and surgical intervention with Kasai portoenterostomy after 3 months of age is significantly associated with poor prognosis for native liver survival. A national Taiwan infant stool color card (SCC) screening program has entirely eliminated late Kasai portoenterostomy >90 days of age and improved native liver survival. A recent large-scale prospective cohort study in British Columbia, Canada, indicated that distribution of SCC on the maternity ward was feasible, led to high utilization rate, and was cost-effective. The aim of the present study was to assess the generalizability of this screening strategy in another Canadian jurisdiction with a different sociodemographic profile.<br><br>METHODS: An SCC was distributed to families of newborns discharged at St Mary's Hospital Center, Montreal, Quebec. Families were instructed to monitor their infant's stool color for 21 days and then complete and mail the SCC to the study center. Phone surveys to families who did not return cards were used to estimate total card utilization rate.<br><br>RESULTS: Two thousand two hundred forty-six infants were eligible for inclusion; 99.9% were enrolled. Mail SCC return rate was 63.3%. No cases of BA were identified. All of the 118 families who completed the phone survey reported that they had utilized the SCC. Conservative and optimistic estimates for total card utilization rates were 82% and 100%, respectively.<br><br>CONCLUSIONS: The high enrollment and utilization rates in this screening study strongly support the feasibility of implementing a Canadian SCC screening program to improve outcomes of children with BA.}, }
@article {pmid26591033, year = {2015}, author = {Vela-Bahena, LE and Vergara, R and Vite, L and Ramos, C}, title = {[Postpartum treatment without interrupting breastfeeding in a patient with Chagas disease].}, journal = {Ginecologia y obstetricia de Mexico}, volume = {83}, number = {8}, pages = {487-493}, pmid = {26591033}, issn = {0300-9041}, mesh = {*Breast Feeding ; Chagas Disease/*drug therapy ; Female ; Humans ; Nitroimidazoles/*therapeutic use ; Postpartum Period ; Trypanocidal Agents/*therapeutic use ; Young Adult ; }, abstract = {Chagas disease is a problem of global public health. It is caused by the protozoan Trypanosoma cruzi, which is acquired through exposure to infected triatomine feces, blood transfusion, organ transplantation, orally, by laboratory accidents and congenitally (mother-child); the latter is a public health problem in endemic countries and is the most common form in non-endemic countries. In Mexico, there are few studies on congenital transmission of Chagas disease. The majority of pregnant women with Chagas disease are chronic and asymptomatic, and there is a risk of products with low birth weight and abortions, yet most infants are asymptomatic and treatment in pregnancy is contraindicated. Here, we report a case of a 24-year-old who was diagnosed with Chagas disease by donating blood and confirmed by the State Laboratory of Public Health. Before starting treatment, 13 weeks pregnancy was detected and followed up until the birth; mother was seropositive for Chagas disease and child was negative by parasitological studies. Breastfeeding was initiated at birth and one month, after consulting with experts, treating the mother began with benznidazole for 45 days; in general, the treatment was well tolerated, but the patient remained seropositive.}, }
@article {pmid26586410, year = {2015}, author = {Spector, T and Knight, R}, title = {Authors' reply to Mawer and Wilcox and Mullish and Williams.}, journal = {BMJ (Clinical research ed.)}, volume = {351}, number = {}, pages = {h6132}, doi = {10.1136/bmj.h6132}, pmid = {26586410}, issn = {1756-1833}, mesh = {Clostridium/*isolation &amp; purification ; Clostridium Infections/*therapy ; Colon/*microbiology ; *Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid26585376, year = {2015}, author = {Mullish, BH and Williams, HR}, title = {Obstacles to establishing an NHS faecal transplant programme.}, journal = {BMJ (Clinical research ed.)}, volume = {351}, number = {}, pages = {h6043}, doi = {10.1136/bmj.h6043}, pmid = {26585376}, issn = {1756-1833}, mesh = {Clostridium/*isolation &amp; purification ; Clostridium Infections/*therapy ; Colon/*microbiology ; *Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid26584845, year = {2015}, author = {Mawer, DP and Wilcox, MH}, title = {Clarifying the management of Clostridium difficile infection.}, journal = {BMJ (Clinical research ed.)}, volume = {351}, number = {}, pages = {h6130}, doi = {10.1136/bmj.h6130}, pmid = {26584845}, issn = {1756-1833}, mesh = {Clostridium/*isolation &amp; purification ; Clostridium Infections/*therapy ; Colon/*microbiology ; *Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid26582185, year = {2016}, author = {Chaplin, A and Parra, P and Laraichi, S and Serra, F and Palou, A}, title = {Calcium supplementation modulates gut microbiota in a prebiotic manner in dietary obese mice.}, journal = {Molecular nutrition &amp; food research}, volume = {60}, number = {2}, pages = {468-480}, doi = {10.1002/mnfr.201500480}, pmid = {26582185}, issn = {1613-4133}, mesh = {Angiopoietin-Like Protein 4 ; Angiopoietins/genetics ; Animals ; Bifidobacterium/drug effects ; Calcium, Dietary/*pharmacology ; Diet, High-Fat/adverse effects ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/genetics ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism ; Male ; Mice, Inbred C57BL ; Obesity/diet therapy/etiology/*microbiology ; Organ Size/drug effects ; *Prebiotics ; }, abstract = {SCOPE: Dietary calcium has been inversely associated with body fat and energy balance. The main scope of this study has been to assess the potential contribution of gut microbiota on energy regulation mediated by calcium.<br><br>METHODS AND RESULTS: Gut microbiota in C57BL/6J mice receiving calcium supplementation under a high-fat (HF) diet were analysed by PCR and their relationships with host metabolic parameters were determined. Calcium conferred a prebiotic-like effect on gut microbiota, and animals presented lower plasmatic endotoxin levels, increased expression of angiopoietin-like 4 in intestine and lower hepatic lipid content, although increased expression of stress markers in adipose tissue and of inflammation in liver was also found. To determine whether slimming effects could be transferred to obese mice, a faecal microbial transplant (FMT) was carried out, showing that host bacteria grown under a HF diet could not be superseded by those from calcium-fed animals. Therefore, FMT was not able to transfer the beneficial effects of calcium.<br><br>CONCLUSION: In conclusion, calcium modulated gut microbiota in a prebiotic manner, establishing a host cross-talk and promoting a healthier metabolic profile. However, lack of effectiveness of FMT suggests the need of further appropriate dietary factors in addition to the bacteria per se.}, }
@article {pmid26581409, year = {2015}, author = {Hevia, A and Delgado, S and Margolles, A and Sánchez, B}, title = {Application of density gradient for the isolation of the fecal microbial stool component and the potential use thereof.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {16807}, pmid = {26581409}, issn = {2045-2322}, mesh = {Bacteria/*isolation &amp; purification ; Biodiversity ; Centrifugation, Density Gradient/*methods ; Feces/*microbiology ; Humans ; Microbiota ; Multivariate Analysis ; Phylogeny ; }, abstract = {The idea of considering the gut microbiota as a virtual human organ has led to the concept of fecal microbiota transplantation (FMT), which has recently been extremely successful in the treatment of cases of recurrent Clostridium difficile infection. Administration of safe, viable, and representative fecal microbiota is crucial for FMT. To our knowledge, suitable techniques and systematic conditions for separating the fecal microbiota from stool samples have not been thoroughly investigated. In this work we show the potential to separate stool microorganisms from the rest of fecal material using a procedure with a Nycodenz® density gradient, yielding 10(10) viable bacteria per two grams of feces. This procedure did not affect the original microbiota composition in terms of viability, distribution and proportions, as assessed by a phylogenetic metagenomic approach. Obtaining the fecal microbiota by concentration and separation of the microorganisms from the rest of the stool components would allow the standardization of its recovery and its long-term preservation. FMT or similar microbiota restoration therapies could be used for the treatment of several disorders, or even for aesthetic purposes, so the method described in our work may contribute to the setting of the basis for the development of safe and standardized products.}, }
@article {pmid26571773, year = {2015}, author = {Ohkusa, T and Koido, S}, title = {[Gut Microbiota and Internal Diseases: Update Information. Topics: II. Fecal microbiota transplantation and its clinical application].}, journal = {Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine}, volume = {104}, number = {1}, pages = {42-47}, doi = {10.2169/naika.104.42}, pmid = {26571773}, issn = {0021-5384}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Bacterial Infections/diagnosis/drug therapy ; Clostridioides difficile/drug effects/*isolation &amp; purification ; *Feces ; Gastrointestinal Tract/*microbiology ; Humans ; *Microbiota ; }, }
@article {pmid26566371, year = {2015}, author = {Bowman, KA and Broussard, EK and Surawicz, CM}, title = {Fecal microbiota transplantation: current clinical efficacy and future prospects.}, journal = {Clinical and experimental gastroenterology}, volume = {8}, number = {}, pages = {285-291}, pmid = {26566371}, issn = {1178-7023}, abstract = {Fecal microbiota transplantation (FMT) has gained mainstream attention with its remarkable efficacy in treating recurrent Clostridium difficile infection (RCDI) when there are no other effective therapies. Methods of selecting donors and routes of administration vary among studies, but there are now randomized controlled trials showing efficacy of FMT in treating RCDI. Ongoing trials of FMT for other disease such as inflammatory bowel disease are underway; this therapy should not be used for these conditions unless there is strong evidence for efficacy. Long-term safety data are sorely needed, as well as clarification of regulatory concerns.}, }
@article {pmid26565971, year = {2016}, author = {Jackson, M and Olefson, S and Machan, JT and Kelly, CR}, title = {A High Rate of Alternative Diagnoses in Patients Referred for Presumed Clostridium difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {50}, number = {9}, pages = {742-746}, pmid = {26565971}, issn = {1539-2031}, support = {R21 DK093839/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Cohort Studies ; Diagnosis, Differential ; Diarrhea/etiology ; Enterocolitis, Pseudomembranous/complications/diagnosis/*epidemiology/microbiology ; Female ; Humans ; Irritable Bowel Syndrome/complications/diagnosis/epidemiology/microbiology ; Male ; Middle Aged ; Referral and Consultation ; Retrospective Studies ; Rhode Island/epidemiology ; Young Adult ; }, abstract = {GOALS: We evaluated a cohort of patients referred to our center for presumed recurrent Clostridium difficile infection (CDI) to determine final diagnoses and outcomes.<br><br>BACKGROUND: As rates of CDI have increased, more patients are diagnosed with recurrent CDI and other sequelae of the infection. Distinguishing symptomatic patients with CDI from those who are colonized with an alternative etiology of diarrheal symptoms may be challenging.<br><br>MATERIALS AND METHODS: We performed a retrospective review of 117 patients referred to our center for recurrent CDI between January 2013 and June 2014. Data collected included demographics, the referring provider, previous anti-CDI treatment, and significant medical conditions. In addition, we gathered data on atypical features of CDI and investigations obtained to investigate the etiology of symptoms. Outcomes included rates of alternative diagnoses and the accuracy of CDI diagnosis by the referral source.<br><br>RESULTS: The mean age was 61 years, and 70% were female. About 29 patients (25%) were determined to have a non-CDI diagnosis. Most common alternative diagnoses included irritable bowel syndrome (18 patients: 62%) and inflammatory bowel disease (3 patients:10%). The age was inversely correlated with the rate of non-CDI diagnosis (P=0.016). Of the remaining 88 (75%) patients with a confirmed diagnosis of CDI, 25 (28%) received medical therapy alone and 63 (72%) underwent fecal microbiota transplantation.<br><br>CONCLUSIONS: Among patients referred to our center for recurrent CDI, a considerable percentage did not have CDI, but rather an alternative diagnosis, most commonly irritable bowel syndrome. The rate of alternative diagnosis correlated inversely with age. Providers should consider other etiologies of diarrhea in patients presenting with features atypical of recurrent CDI.}, }
@article {pmid26565670, year = {2016}, author = {Ünal, CM and Steinert, M}, title = {Novel therapeutic strategies for Clostridium difficile infections.}, journal = {Expert opinion on therapeutic targets}, volume = {20}, number = {3}, pages = {269-285}, doi = {10.1517/14728222.2016.1090428}, pmid = {26565670}, issn = {1744-7631}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Clostridioides difficile/*drug effects/isolation &amp; purification/pathogenicity ; Clostridium Infections/*drug therapy/microbiology ; Drug Design ; Hospitalization ; Humans ; Length of Stay ; }, abstract = {INTRODUCTION: In recent years, Clostridium difficile has become the primary cause of antibiotic-associated diarrhea and pseudomembranous colitis, resulting in long and complicated hospital stays that represent a serious burden for patients as well as health care systems. Currently, conservative treatment of C. difficile infection (CDI) relies on the antibiotics vancomycin, metronidazole or fidaxomicin, or in case of multiple recurrences, fecal microbiota transplantation (FMT).<br><br>AREAS COVERED: The fast-spreading, epidemic nature of this pathogen urgently necessitates the search for alternative treatment strategies as well as antibiotic targets. Accordingly, in this review, we highlight the recent findings regarding virulence associated traits of C. difficile, evaluate their potential as alternative drug targets, and present current efforts in designing inhibitory compounds, with the aim of pointing out possibilities for future treatment strategies.<br><br>EXPERT OPINION: Increased attention on systematic analysis of the virulence mechanisms of C. difficile has already led to the identification of several alternative drug targets. In the future, applying state of the art 'omics' and the development of novel infection models that mimic the human gut, a highly complex ecological niche, will unveil the genomic and metabolic plasticity of this pathogen and will certainly help dealing with future challenges.}, }
@article {pmid26565008, year = {2016}, author = {Orenstein, R and Dubberke, E and Hardi, R and Ray, A and Mullane, K and Pardi, DS and Ramesh, MS and , }, title = {Safety and Durability of RBX2660 (Microbiota Suspension) for Recurrent Clostridium difficile Infection: Results of the PUNCH CD Study.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {62}, number = {5}, pages = {596-602}, doi = {10.1093/cid/civ938}, pmid = {26565008}, issn = {1537-6591}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Clostridioides difficile ; Diarrhea/therapy ; Enema ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Humans ; Male ; *Microbiota ; Middle Aged ; Prospective Studies ; Recurrence ; }, abstract = {BACKGROUND: Managing recurrent Clostridium difficile infection (CDI) presents a significant challenge for clinicians and patients. Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent CDI, yet availability of a standardized, safe, and effective product has been lacking. Our aim in this study was to assess the safety and effectiveness of RBX2660 (microbiota suspension), a commercially prepared FMT drug manufactured using standardized processes and available in a ready-to-use format.<br><br>METHODS: Patients with at least 2 recurrent CDI episodes or at least 2 severe episodes resulting in hospitalization were enrolled in a prospective, multicenter open-label study of RBX2660 administered via enema. Intensive surveillance for adverse events (AEs) was conducted daily for 7 days following treatment and then at 30 days, 60 days, 3 months, and 6 months. The primary objective was product-related AEs. A secondary objective was CDI-associated diarrhea resolution at 8 weeks.<br><br>RESULTS: Of the 40 patients enrolled at 11 centers in the United States between 15 August 2013 and 16 December 2013, 34 received at least 1 dose of RBX2660 and 31 completed 6-month follow-up. Overall efficacy was 87.1% (16 with 1 dose and 11 with 2 doses). Of 188 reported AEs, diarrhea, flatulence, abdominal pain/cramping, and constipation were most common. The frequency and severity of AEs decreased over time. Twenty serious AEs were reported in 7 patients; none were related to RBX2660 or its administration.<br><br>CONCLUSIONS: Among patients with recurrent or severe CDI, administration of RBX2660 via enema appears to be safe and effective.<br><br>CLINICAL TRIALS REGISTRATION: NCT01925417.}, }
@article {pmid26552345, year = {2015}, author = {Kovatcheva-Datchary, P and Nilsson, A and Akrami, R and Lee, YS and De Vadder, F and Arora, T and Hallen, A and Martens, E and Björck, I and Bäckhed, F}, title = {Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella.}, journal = {Cell metabolism}, volume = {22}, number = {6}, pages = {971-982}, doi = {10.1016/j.cmet.2015.10.001}, pmid = {26552345}, issn = {1932-7420}, mesh = {Aged ; Animals ; Bacteroides/genetics/growth &amp; development/physiology ; Blood Glucose/analysis ; Cross-Over Studies ; Dietary Fiber/*pharmacology ; Feces/microbiology ; Female ; Glucose/*metabolism ; Glycogen/metabolism ; Humans ; Hydrogen/metabolism ; Insulin/blood ; Intestines/microbiology ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota/*drug effects ; Middle Aged ; Prevotella/genetics/*growth &amp; development/physiology ; RNA, Ribosomal, 16S/chemistry/metabolism ; }, abstract = {The gut microbiota plays an important role in human health by interacting with host diet, but there is substantial inter-individual variation in the response to diet. Here we compared the gut microbiota composition of healthy subjects who exhibited improved glucose metabolism following 3-day consumption of barley kernel-based bread (BKB) with those who responded least to this dietary intervention. The Prevotella/Bacteroides ratio was higher in responders than non-responders after BKB. Metagenomic analysis showed that the gut microbiota of responders was enriched in Prevotella copri and had increased potential to ferment complex polysaccharides after BKB. Finally, germ-free mice transplanted with microbiota from responder human donors exhibited improved glucose metabolism and increased abundance of Prevotella and liver glycogen content compared with germ-free mice that received non-responder microbiota. Our findings indicate that Prevotella plays a role in the BKB-induced improvement in glucose metabolism observed in certain individuals, potentially by promoting increased glycogen storage.}, }
@article {pmid26549493, year = {2015}, author = {Rodriguez, C and Taminiau, B and Van Broeck, J and Delmée, M and Daube, G}, title = {Clostridium difficile infection and intestinal microbiota interactions.}, journal = {Microbial pathogenesis}, volume = {89}, number = {}, pages = {201-209}, doi = {10.1016/j.micpath.2015.10.018}, pmid = {26549493}, issn = {1096-1208}, mesh = {Clostridioides difficile/*growth &amp; development ; Clostridium Infections/*microbiology ; *Gastrointestinal Microbiome ; Humans ; *Microbial Interactions ; }, abstract = {Clostridium difficile remains the leading cause of healthcare-associated diarrhoea and outbreaks continue to occur worldwide. Aside from nosocomial C. difficile infection, the bacterium is also increasingly important as a community pathogen. Furthermore, asymptomatic carriage of C. difficile in neonates, adults and animals is also well recognised. The investigation of the gut's microbial communities, in both healthy subjects and patients suffering C. difficile infection (CDI), provides findings and information relevant for developing new successful approaches for its treatment, such as faecal microbiota transplantation, or for the prophylaxis of the infection by modification of the gut microbiota using functional foods and beverages. The analysis of all available data shows new insights into the role of intestinal microbiota in health and disease.}, }
@article {pmid26548336, year = {2015}, author = {Thomas, LV and Suzuki, K and Zhao, J}, title = {Probiotics: a proactive approach to health. A symposium report.}, journal = {The British journal of nutrition}, volume = {114 Suppl 1}, number = {}, pages = {S1-15}, doi = {10.1017/S0007114515004043}, pmid = {26548336}, issn = {1475-2662}, mesh = {Anti-Bacterial Agents/adverse effects ; Bacteria/classification ; Bacterial Infections/prevention &amp; control ; Child ; Diarrhea/chemically induced/prevention &amp; control ; Gastrointestinal Diseases/*prevention &amp; control ; HIV Infections ; Humans ; Integrative Medicine ; Intestinal Mucosa/immunology/microbiology ; Metabolic Diseases/*prevention &amp; control ; Microbiota ; Neoplasms ; Practice Guidelines as Topic ; Probiotics/*administration &amp; dosage/*pharmacology ; }, abstract = {This report summarises talks given at the 8th International Yakult Symposium, held on 23-24 April 2015 in Berlin. Two presentations explored different aspects of probiotic intervention: the small intestine as a probiotic target and inclusion of probiotics into integrative approaches to gastroenterology. Probiotic recommendations in gastroenterology guidelines and current data on probiotic efficacy in paediatric patients were reviewed. Updates were given on probiotic and gut microbiota research in obesity and obesity-related diseases, the gut-brain axis and development of psychobiotics, and the protective effects of equol-producing strains for prostate cancer. Recent studies were presented on probiotic benefit for antibiotic-associated diarrhoea and people with HIV, as well as protection against the adverse effects of a short-term high-fat diet. Aspects of probiotic mechanisms of activity were discussed, including immunomodulatory mechanisms and metabolite effects, the anti-inflammatory properties of Faecalibacterium prausnitzii, the relationship between periodontitis, microbial production of butyrate in the oral cavity and ageing, and the pathogenic mechanisms of Campylobacter. Finally, an insight was given on a recent expert meeting, which re-examined the probiotic definition, advised on the appropriate use and scope of the term and outlined different probiotic categories and the prevalence of different mechanisms of activity.}, }
@article {pmid26544826, year = {2015}, author = {Oh, HK and Hwang, JY and Kang, SB}, title = {The Authors Reply.}, journal = {Diseases of the colon and rectum}, volume = {58}, number = {12}, pages = {e456-7}, doi = {10.1097/DCR.0000000000000481}, pmid = {26544826}, issn = {1530-0358}, mesh = {Anal Canal/*injuries ; Animals ; Biocompatible Materials/*therapeutic use ; Fecal Incontinence/*therapy ; *Muscle Contraction ; Myoblasts, Skeletal/*transplantation ; Polyesters/*therapeutic use ; }, }
@article {pmid26544825, year = {2015}, author = {Sammour, T}, title = {Ethics in Animal Research: Explicit Explanation Is Necessary.}, journal = {Diseases of the colon and rectum}, volume = {58}, number = {12}, pages = {e456}, doi = {10.1097/DCR.0000000000000480}, pmid = {26544825}, issn = {1530-0358}, mesh = {Anal Canal/*injuries ; Animals ; Biocompatible Materials/*therapeutic use ; Fecal Incontinence/*therapy ; *Muscle Contraction ; Myoblasts, Skeletal/*transplantation ; Polyesters/*therapeutic use ; }, }
@article {pmid26541990, year = {2016}, author = {Singh, S and Jing, E and Stollman, N}, title = {Self-Limited Sepsis Syndrome Following Fecal Microbiota Therapy for Refractory C. difficile Infection.}, journal = {Digestive diseases and sciences}, volume = {61}, number = {9}, pages = {2488-2491}, pmid = {26541990}, issn = {1573-2568}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/complications/*diagnostic imaging/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Middle Aged ; Sepsis/complications/*diagnostic imaging/*therapy ; }, }
@article {pmid26541610, year = {2015}, author = {Vétizou, M and Pitt, JM and Daillère, R and Lepage, P and Waldschmitt, N and Flament, C and Rusakiewicz, S and Routy, B and Roberti, MP and Duong, CP and Poirier-Colame, V and Roux, A and Becharef, S and Formenti, S and Golden, E and Cording, S and Eberl, G and Schlitzer, A and Ginhoux, F and Mani, S and Yamazaki, T and Jacquelot, N and Enot, DP and Bérard, M and Nigou, J and Opolon, P and Eggermont, A and Woerther, PL and Chachaty, E and Chaput, N and Robert, C and Mateus, C and Kroemer, G and Raoult, D and Boneca, IG and Carbonnel, F and Chamaillard, M and Zitvogel, L}, title = {Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota.}, journal = {Science (New York, N.Y.)}, volume = {350}, number = {6264}, pages = {1079-1084}, pmid = {26541610}, issn = {1095-9203}, support = {R01 CA161879/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Anti-Bacterial Agents/pharmacology ; Antibodies, Monoclonal/adverse effects/*therapeutic use ; Bacteroides/*immunology ; CTLA-4 Antigen/*antagonists &amp; inhibitors/immunology ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/drug effects/*immunology ; Germ-Free Life/immunology ; Humans ; Immunologic Memory ; Immunotherapy ; Intestines/immunology/microbiology ; Ipilimumab ; Male ; Melanoma/*therapy ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Skin Neoplasms/*therapy ; T-Lymphocytes/immunology ; }, abstract = {Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.}, }
@article {pmid26541606, year = {2015}, author = {Sivan, A and Corrales, L and Hubert, N and Williams, JB and Aquino-Michaels, K and Earley, ZM and Benyamin, FW and Lei, YM and Jabri, B and Alegre, ML and Chang, EB and Gajewski, TF}, title = {Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy.}, journal = {Science (New York, N.Y.)}, volume = {350}, number = {6264}, pages = {1084-1089}, pmid = {26541606}, issn = {1095-9203}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; T32 CA009594/CA/NCI NIH HHS/United States ; T32 AI007090/AI/NIAID NIH HHS/United States ; R01 AI115716/AI/NIAID NIH HHS/United States ; P30 DK42086/DK/NIDDK NIH HHS/United States ; 5T32CA009594-25/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/*therapeutic use ; B7-H1 Antigen/*immunology ; Bifidobacterium/genetics/*immunology ; CD8-Positive T-Lymphocytes/immunology ; Dendritic Cells/immunology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Gene Expression Regulation ; Humans ; Immunity/genetics ; Immunotherapy/methods ; Lymphocyte Activation ; Melanoma/*immunology/*therapy ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Skin Neoplasms/*immunology/*therapy ; Symbiosis ; T-Lymphocytes/immunology ; Tumor Microenvironment/immunology ; }, abstract = {T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)-specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8(+) T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.}, }
@article {pmid26537324, year = {2015}, author = {Osada, T and Ishikawa, D and Watanabe, S}, title = {[Fecal microbiota transplantation therapy for patients with gastrointestinal tract diseases].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {112}, number = {11}, pages = {1973-1981}, doi = {10.11405/nisshoshi.112.1973}, pmid = {26537324}, issn = {0446-6586}, mesh = {Animals ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation/methods ; Humans ; Irritable Bowel Syndrome/*therapy ; Mice ; }, }
@article {pmid26525290, year = {2015}, author = {Babickova, J and Gardlik, R}, title = {Pathological and therapeutic interactions between bacteriophages, microbes and the host in inflammatory bowel disease.}, journal = {World journal of gastroenterology}, volume = {21}, number = {40}, pages = {11321-11330}, pmid = {26525290}, issn = {2219-2840}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacteria/drug effects/*virology ; *Bacteriophages ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Host-Pathogen Interactions ; Humans ; Inflammatory Bowel Diseases/diagnosis/immunology/*microbiology/therapy ; Intestines/drug effects/immunology/*microbiology ; Probiotics/therapeutic use ; }, abstract = {The intestinal microbiome is a dynamic system of interactions between the host and its microbes. Under physiological conditions, a fine balance and mutually beneficial relationship is present. Disruption of this balance is a hallmark of inflammatory bowel disease (IBD). Whether an altered microbiome is the consequence or the cause of IBD is currently not fully understood. The pathogenesis of IBD is believed to be a complex interaction between genetic predisposition, the immune system and environmental factors. In the recent years, metagenomic studies of the human microbiome have provided useful data that are helping to assemble the IBD puzzle. In this review, we summarize and discuss current knowledge on the composition of the intestinal microbiota in IBD, host-microbe interactions and therapeutic possibilities using bacteria in IBD. Moreover, an outlook on the possible contribution of bacteriophages in the pathogenesis and therapy of IBD is provided.}, }
@article {pmid26525055, year = {2016}, author = {Fang, S and Kraft, CS and Dhere, T and Srinivasan, J and Begley, B and Weinstein, D and Shaffer, VO}, title = {Successful treatment of chronic Pouchitis utilizing fecal microbiota transplantation (FMT): a case report.}, journal = {International journal of colorectal disease}, volume = {31}, number = {5}, pages = {1093-1094}, doi = {10.1007/s00384-015-2428-y}, pmid = {26525055}, issn = {1432-1262}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Chronic Disease ; *Fecal Microbiota Transplantation ; Humans ; Male ; Pouchitis/drug therapy/pathology/*therapy ; Treatment Outcome ; }, }
@article {pmid26520192, year = {2015}, author = {Gomollón, F}, title = {[Treatment of inflammatory bowel diseases].}, journal = {Gastroenterologia y hepatologia}, volume = {38 Suppl 1}, number = {}, pages = {13-19}, doi = {10.1016/S0210-5705(15)30015-7}, pmid = {26520192}, issn = {0210-5705}, mesh = {Antibodies, Monoclonal/therapeutic use ; Antirheumatic Agents/therapeutic use ; Clinical Trials as Topic ; Fecal Microbiota Transplantation ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents/therapeutic use ; Inflammatory Bowel Diseases/*drug therapy/microbiology/therapy ; Methotrexate/therapeutic use ; Multicenter Studies as Topic ; Oligonucleotides, Antisense/therapeutic use ; Recurrence ; Therapies, Investigational ; Transplantation, Autologous ; }, abstract = {In addition to immunosuppressive drugs and anti-TNF, there are a number of new options in the treatment of inflammatory bowel diseases. Vedolizumab has been approved by the FDA and EMA and has demonstrated utility both in the treatment of ulcerative colitis (UC) and Crohn's disease (CD), even in anti-TNF refractory patients. Other monoclonal antibodies with different targets such as PF-005447659 (antiMAd-CAM1), ustekinumab (anti-IL23/IL12) or MEDI2070 (anti-IL23) have shown promising results in distinct clinical scenarios. Mongersen (antisense oligonucleotide anti-Smad7) and oznimod (an SP-1 modulator) are new alternatives with proven efficacy in clinical trials in CD and UC, respectively. Some data suggest that faecal microbiota transplantation could be efficacious in individual patients, although controlled data do not show clear differences with placebo. Autologous stem-cell transplantation has shown long-term efficacy in "ultra-refractory" CD. The number of possible treatments is constantly increasing, and future research should focus both on the selection of the most appropriate treatment for any given patient and on comparative trials between options.}, }
@article {pmid26519463, year = {2016}, author = {Vermeire, S and Joossens, M and Verbeke, K and Wang, J and Machiels, K and Sabino, J and Ferrante, M and Van Assche, G and Rutgeerts, P and Raes, J}, title = {Donor Species Richness Determines Faecal Microbiota Transplantation Success in Inflammatory Bowel Disease.}, journal = {Journal of Crohn's &amp; colitis}, volume = {10}, number = {4}, pages = {387-394}, pmid = {26519463}, issn = {1876-4479}, mesh = {Adult ; C-Reactive Protein/analysis ; Colitis, Ulcerative/therapy ; Colonoscopy ; Crohn Disease/therapy ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome/physiology ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Male ; Middle Aged ; Treatment Failure ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Faecal microbiota transplantation is a successful therapy for patients with refractory Clostridium difficile infections. It has also been suggested as a treatment option for inflammatory bowel disease, given the role of the intestinal microbiota in this disease. We assessed the impact of faecal microbiota transplantation in patients with inflammatory bowel disease and studied predictors of clinical (non-)response in microbial profiles of donors and patients.<br><br>METHODS: Fourteen refractory patients (8 with ulcerative colitis and 6 with Crohn's disease) underwent ileocolonoscopy with faecal microbiota transplantation through a nasojejunal (n = 9) or rectal (n = 5) tube. Efficacy was assessed by endoscopic healing at week 8, clinical activity scores and C-reactive protein measurement. Faecal microbiota was analysed by 16S rDNA pyrosequencing.<br><br>RESULTS: There was no significant improvement among the 6 patients with Crohn's disease at week 8 following faecal microbiota transplantation. One patient experienced temporary clinical remission for 6 weeks. In contrast, 2/8 patients with ulcerative colitis had endoscopic remission at week 8, and of the 6 remaining patients with ulcerative colitis, 1 reported temporary remission for 6 weeks. The donor microbiota richness and the number of transferred phylotypes were associated with treatment success. Persistent increased C-reactive protein 2 weeks after transplantation was predictive of failure of response.<br><br>CONCLUSION: Faecal microbiota transplantation led to endoscopic and long-term (>2 years) remission in 2 out of 8 ulcerative colitis patients. Higher donor richness was associated with successful transplant. Therefore, faecal microbiota transplantation with donor prescreening could be a treatment option for selected refractory ulcerative colitis patients.}, }
@article {pmid26515636, year = {2015}, author = {Kimura, H and Usui, F and Karasawa, T and Kawashima, A and Shirasuna, K and Inoue, Y and Komada, T and Kobayashi, M and Mizushina, Y and Kasahara, T and Suzuki, K and Iwasaki, Y and Yada, T and Caturegli, P and Takahashi, M}, title = {Immunoproteasome subunit LMP7 Deficiency Improves Obesity and Metabolic Disorders.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {15883}, pmid = {26515636}, issn = {2045-2322}, mesh = {Adiponectin/blood ; Adipose Tissue/metabolism ; Animals ; Antigens, CD/metabolism ; Bone Marrow Transplantation ; Chemokines/metabolism ; Diet, High-Fat ; Energy Metabolism ; Insulin Resistance ; Lipase/metabolism ; Macrophages/immunology/metabolism ; Male ; Metabolic Diseases/metabolism/*pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity ; Obesity/metabolism/*pathology ; Pancreas/enzymology ; Proteasome Endopeptidase Complex/deficiency/*genetics ; Subcutaneous Fat, Abdominal/diagnostic imaging ; Triglycerides/blood ; X-Ray Microtomography ; }, abstract = {Inflammation plays an important role in the development of obesity and metabolic disorders; however, it has not been fully understood how inflammation occurs and is regulated in their pathogenesis. Low-molecular mass protein-7 (LMP7) is a proteolytic subunit of the immunoproteasome that shapes the repertoire of antigenic peptides on major histocompatibility complex class I molecule. In this study, we investigated the role of LMP7 in the development of obesity and metabolic disorders using LMP7-deficient mice. LMP7 deficiency conveyed resistant to obesity, and improved glucose intolerance and insulin sensitivity in mice fed with high-fat diet (HFD). LMP7 deficiency decreased pancreatic lipase expression, increased fecal lipid contents, and inhibited the increase of plasma triglyceride levels upon oral oil administration or HFD feeding. Using bone marrow-transferred chimeric mice, we found that LMP7 in both bone marrow- and non-bone marrow-derived cells contributes to the development of HFD-induced obesity. LMP7 deficiency decreased inflammatory responses such as macrophage infiltration and chemokine expression while it increased serum adiponection levels. These findings demonstrate a novel role for LMP7 and provide new insights into the mechanisms underlying inflammation in the pathophysiology of obesity and metabolic disorders.}, }
@article {pmid26511795, year = {2016}, author = {Schuijt, TJ and Lankelma, JM and Scicluna, BP and de Sousa e Melo, F and Roelofs, JJ and de Boer, JD and Hoogendijk, AJ and de Beer, R and de Vos, A and Belzer, C and de Vos, WM and van der Poll, T and Wiersinga, WJ}, title = {The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia.}, journal = {Gut}, volume = {65}, number = {4}, pages = {575-583}, pmid = {26511795}, issn = {1468-3288}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacterial Load ; Feces/microbiology ; Gastrointestinal Microbiome/*immunology ; *Immunity, Mucosal ; Interleukin-10/metabolism ; Macrophages, Alveolar/immunology/metabolism ; Mice ; Mice, Inbred C57BL ; Pneumonia, Pneumococcal/*immunology/metabolism/microbiology ; Sepsis/immunology/metabolism/microbiology ; Streptococcus pneumoniae/immunology ; Transcriptome ; Tumor Necrosis Factor-alpha/metabolism ; Up-Regulation ; }, abstract = {OBJECTIVE: Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections.<br><br>DESIGN: We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses.<br><br>RESULTS: We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-&#x3b1; and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae.<br><br>CONCLUSIONS: This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut-lung axis in bacterial infections.}, }
@article {pmid26500463, year = {2015}, author = {Lamprecht, M and Bogner, S and Steinbauer, K and Schuetz, B and Greilberger, JF and Leber, B and Wagner, B and Zinser, E and Petek, T and Wallner-Liebmann, S and Oberwinkler, T and Bachl, N and Schippinger, G}, title = {Effects of zeolite supplementation on parameters of intestinal barrier integrity, inflammation, redoxbiology and performance in aerobically trained subjects.}, journal = {Journal of the International Society of Sports Nutrition}, volume = {12}, number = {}, pages = {40}, pmid = {26500463}, issn = {1550-2783}, mesh = {Adult ; Biomarkers/blood ; Cholera Toxin/metabolism ; DNA Damage ; *Dietary Supplements ; Double-Blind Method ; Feces/chemistry ; Female ; Haptoglobins ; Humans ; Inflammation/blood/*drug therapy ; Interleukin-10/blood ; Interleukin-6/blood ; Interleukin-8/blood ; Interleukins/blood ; Intestines/*drug effects ; Male ; Middle Aged ; Nutrition Assessment ; Oxygen Consumption ; Permeability ; Protein Precursors ; Tight Junctions/drug effects ; Tumor Necrosis Factor-alpha/blood ; Zeolites/*pharmacology ; Interleukin-22 ; }, abstract = {BACKGROUND: Zeolites are crystalline compounds with microporous structures of Si-tetrahedrons. In the gut, these silicates could act as adsorbents, ion-exchangers, catalysts, detergents or anti-diarrheic agents. This study evaluated whether zeolite supplementation affects biomarkers of intestinal wall permeability and parameters of oxidation and inflammation in aerobically trained individuals, and whether it could improve their performance.<br><br>METHODS: In a randomized, double-blinded, placebo controlled trial, 52 endurance trained men and women, similar in body fat, non-smokers, 20-50 years, received 1.85&#xa0;g of zeolite per day for 12&#xa0;weeks. Stool samples for determination of intestinal wall integrity biomarkers were collected. From blood, markers of redox biology, inflammation, and DNA damage were determined at the beginning and the end of the study. In addition, VO2max and maximum performance were evaluated at baseline and after 12&#xa0;weeks of treatment. For statistical analyses a 2-factor ANOVA was used.<br><br>RESULTS: At baseline both groups showed slightly increased stool zonulin concentrations above normal. After 12&#xa0;weeks with zeolite zonulin was significantly (p&#x2009;<&#x2009;0.05) decreased in the supplemented group. IL-10 increased tendentially (p&#x2009;<&#x2009;0.1) in the zeolite group. There were no significant changes observed in the other measured parameters.<br><br>CONCLUSIONS: Twelve&#xa0;weeks of zeolite supplementation exerted beneficial effects on intestinal wall integrity as indicated via decreased concentrations of the tight junction modulator zonulin. This was accompanied by mild anti-inflammatory effects in this cohort of aerobically trained subjects. Further research is needed to explore mechanistic explanations for the observations in this study.}, }
@article {pmid26488817, year = {2015}, author = {Haghikia, A and Jörg, S and Duscha, A and Berg, J and Manzel, A and Waschbisch, A and Hammer, A and Lee, DH and May, C and Wilck, N and Balogh, A and Ostermann, AI and Schebb, NH and Akkad, DA and Grohme, DA and Kleinewietfeld, M and Kempa, S and Thöne, J and Demir, S and Müller, DN and Gold, R and Linker, RA}, title = {Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine.}, journal = {Immunity}, volume = {43}, number = {4}, pages = {817-829}, doi = {10.1016/j.immuni.2015.09.007}, pmid = {26488817}, issn = {1097-4180}, mesh = {Animals ; Autoimmunity/*drug effects ; Central Nervous System/*immunology ; Dietary Fats/*pharmacology/toxicity ; Duodenum/*immunology/metabolism/microbiology ; Encephalomyelitis, Autoimmune, Experimental/*etiology/immunology/metabolism ; Fatty Acids/chemistry/*pharmacology/toxicity ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Gene Expression Regulation/immunology ; Lauric Acids/toxicity ; Liver X Receptors ; Lymphopoiesis/*drug effects ; MAP Kinase Signaling System ; Mice ; Molecular Weight ; Orphan Nuclear Receptors/biosynthesis/genetics ; Receptors, G-Protein-Coupled/biosynthesis/genetics ; Spleen/immunology/pathology ; T-Lymphocyte Subsets/*drug effects/immunology/metabolism ; T-Lymphocytes, Regulatory/immunology ; Th1 Cells/immunology ; Th17 Cells/immunology ; Transcriptome ; }, abstract = {Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and autoimmunity. We report that long-chain fatty acids (LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway. We used experimental autoimmune encephalomyelitis (EAE) as a model of T cell-mediated autoimmunity to show that LCFAs consistently decreased SCFAs in the gut and exacerbated disease by expanding pathogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on lamina-propria-derived Treg cells. These data demonstrate a direct dietary impact on intestinal-specific, and subsequently central nervous system-specific, Th cell responses in autoimmunity, and thus might have therapeutic implications for autoimmune diseases such as multiple sclerosis.}, }
@article {pmid26487671, year = {2015}, author = {Spector, T and Knight, R}, title = {Faecal transplants.}, journal = {BMJ (Clinical research ed.)}, volume = {351}, number = {}, pages = {h5149}, doi = {10.1136/bmj.h5149}, pmid = {26487671}, issn = {1756-1833}, mesh = {Clostridium/*isolation &amp; purification ; Clostridium Infections/*therapy ; Colon/*microbiology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; *Microbiota ; }, }
@article {pmid26486102, year = {2016}, author = {Kamboj, M and Sheahan, A and Sun, J and Taur, Y and Robilotti, E and Babady, E and Papanicolaou, G and Jakubowski, A and Pamer, E and Sepkowitz, K}, title = {Transmission of Clostridium difficile During Hospitalization for Allogeneic Stem Cell Transplant.}, journal = {Infection control and hospital epidemiology}, volume = {37}, number = {1}, pages = {8-15}, pmid = {26486102}, issn = {1559-6834}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Carrier State/diagnosis/microbiology/*transmission ; *Clostridioides difficile/genetics ; Clostridium Infections/diagnosis/microbiology/*transmission ; Cross Infection/diagnosis/microbiology/*transmission ; Feces/microbiology ; Female ; Genotype ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Multilocus Sequence Typing ; Spatio-Temporal Analysis ; Transplantation, Homologous ; }, abstract = {OBJECTIVE To determine the role of unit-based transmission that accounts for cases of early Clostridium difficile infection (CDI) during hospitalization for allogeneic stem cell transplant. SETTING Stem cell transplant unit at a tertiary care cancer center. METHODS Serially collected stool from patients admitted for transplant was screened for toxigenic C. difficile through the hospital stay and genotyping was performed by multilocus sequence typing. In addition, isolates retrieved from cases of CDI that occurred in other patients hospitalized on the same unit were similarly characterized. Transmission links were established by time-space clustering of cases and carriers of shared toxigenic C. difficile strains. RESULTS During the 27-month period, 1,099 samples from 264 patients were screened, 69 of which had evidence of toxigenic C. difficile; 52 patients developed CDI and 17 were nonsymptomatic carriers. For the 52 cases, 41 had evidence of toxigenic C. difficile on the first study sample obtained within a week of admission, among which 22 were positive within the first 48 hours. A total of 24 sequence types were isolated from this group; 1 patient had infection with the NAP1 strain. A total of 11 patients had microbiologic evidence of acquisition; donor source could be established in half of these cases. CONCLUSIONS Most cases of CDI after stem cell transplant represent delayed onset disease in nonsymptomatic carriers. Transmission on stem cell transplant unit was confirmed in 19% of early CDI cases in our cohort with a probable donor source established in half of the cases.}, }
@article {pmid26485102, year = {2016}, author = {Weingarden, AR and Chen, C and Zhang, N and Graiziger, CT and Dosa, PI and Steer, CJ and Shaughnessy, MK and Johnson, JR and Sadowsky, MJ and Khoruts, A}, title = {Ursodeoxycholic Acid Inhibits Clostridium difficile Spore Germination and Vegetative Growth, and Prevents the Recurrence of Ileal Pouchitis Associated With the Infection.}, journal = {Journal of clinical gastroenterology}, volume = {50}, number = {8}, pages = {624-630}, pmid = {26485102}, issn = {1539-2031}, support = {R21 AI114722/AI/NIAID NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Bile Acids and Salts/metabolism ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*drug therapy/pathology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; In Vitro Techniques ; Middle Aged ; Pouchitis/*drug therapy/microbiology ; Recurrence ; Treatment Outcome ; Ursodeoxycholic Acid/*administration &amp; dosage/pharmacology ; }, abstract = {GOALS: To test whether ursodeoxycholic acid (UDCA) is inhibitory to Clostridium difficile and can be used in the treatment of C. difficile-associated ileal pouchitis.<br><br>BACKGROUND: The restoration of secondary bile metabolism may be the key mechanism for fecal microbiota transplantation (FMT) in treating recurrent C. difficile infections (RCDI). Therefore, it is possible that exogenous administration of inhibitory bile acids may be used directly as nonantibiotic therapeutics for this indication. The need for such a treatment alternative is especially significant in patients with refractory C. difficile-associated pouchitis, where the efficacy of FMT may be limited.<br><br>STUDY: We measured the ability of UDCA to suppress the germination and the vegetative growth of 11 clinical isolate strains of C. difficile from patients treated with FMT for RCDI. In addition, we used oral UDCA to treat a patient with RCDI pouchitis that proved refractory to multiple antibiotic treatments and FMT.<br><br>RESULTS: UDCA was found to be inhibitory to the germination and the vegetative growth of all C. difficile strains tested. Fecal concentrations of UDCA from the patient with RCDI pouchitis exceeded levels necessary to inhibit the germination and the growth of C. difficile in vitro. The patient has remained infection free for over 10 months after the initiation of UDCA.<br><br>CONCLUSIONS: UDCA can be considered as a therapeutic option in patients with C. difficile-associated pouchitis. Further studies need to be conducted to define the optimal dose and duration of such a treatment. In addition, bile acid derivatives inhibitory to C. difficile that are able to achieve high intracolonic concentrations may be developed as therapeutics for RCDI colitis.}, }
@article {pmid26478682, year = {2015}, author = {Paramsothy, S and Walsh, AJ and Borody, T and Samuel, D and van den Bogaerde, J and Leong, RW and Connor, S and Ng, W and Mitchell, HM and Kaakoush, NO and Kamm, MA}, title = {Gastroenterologist perceptions of faecal microbiota transplantation.}, journal = {World journal of gastroenterology}, volume = {21}, number = {38}, pages = {10907-10914}, pmid = {26478682}, issn = {2219-2840}, mesh = {*Attitude of Health Personnel ; Australia ; *Clostridioides difficile ; Colitis, Ulcerative/therapy ; Crohn Disease/therapy ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Gastroenterology ; Health Services Accessibility ; Humans ; Irritable Bowel Syndrome/therapy ; Perception ; }, abstract = {AIM: To explore gastroenterologist perceptions towards and experience with faecal microbiota transplantation (FMT).<br><br>METHODS: A questionnaire survey consisting of 17 questions was created to assess gastroenterologists' attitude towards and experience with FMT. This was anonymously distributed in hard copy format amongst attendees at gastroenterology meetings in Australia between October 2013 and April 2014. Basic descriptive statistical analyses were performed.<br><br>RESULTS: Fifty-two clinicians participated. Twenty one percent had previously referred patients for FMT, 8% more than once. Ninety percent would refer patients with Clostridium difficile infection (CDI) for FMT if easily available, 37% for ulcerative colitis, 13% for Crohn's disease and 6% for irritable bowel syndrome. Six percent would not refer any indication, including recurrent CDI. Eighty-six percent would enroll patients in FMT clinical trials. Thirty-seven percent considered the optimal mode of FMT administration transcolonoscopic, 17% nasoduodenal, 13% enema and 8% oral capsule. The greatest concerns regarding FMT were: 42% lack of evidence, 12% infection risk, 10% non infectious adverse effects/lack of safety data, 10% aesthetic, 10% lack of efficacy, 4% disease exacerbation, and 2% inappropriate use; 6% had no concerns. Seventy seven percent believed there is a lack of accessibility while 52% had an interest in learning how to provide FMT. Only 6% offered FMT at their institution.<br><br>CONCLUSION: Despite general enthusiasm, most gastroenterologists have limited experience with, or access to, FMT. The greatest concerns were lack of supportive evidence and safety issues. However a significant proportion would refer indications other than CDI for FMT despite insufficient evidence. These data provide guidance on where education and training are required.}, }
@article {pmid26476344, year = {2016}, author = {Barrios, C and Spector, TD and Menni, C}, title = {Blood, urine and faecal metabolite profiles in the study of adult renal disease.}, journal = {Archives of biochemistry and biophysics}, volume = {589}, number = {}, pages = {81-92}, doi = {10.1016/j.abb.2015.10.006}, pmid = {26476344}, issn = {1096-0384}, support = {MR/M004422/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Animals ; Blood Chemical Analysis/*methods ; Feces/*chemistry ; Humans ; Kidney Diseases/blood/*metabolism/urine ; Metabolomics/*methods ; Urinalysis/*methods ; }, abstract = {Chronic kidney disease (CKD) is a major public health burden and to date traditional biomarkers of renal function (such as serum creatinine and cystatin C) are unable to identify at-risk individuals before the disease process is well under way. To help preventive strategies and maximize the potential for effective interventions, it is important to characterise the molecular changes that take place in the development of renal damage. Metabolomics is a promising tool to identify markers of renal disease since the kidneys are involved in the handling of major biochemical classes of metabolites. These metabolite levels capture a snap-shot of the metabolic profile of the individual, allowing for the potential identification of early biomarkers, and the monitoring of real-time kidney function. In this review, we describe the current status of the identification of blood/urine/faecal metabolic biomarkers in different entities of kidney diseases including: acute kidney injury, chronic kidney disease, renal transplant, diabetic nephropathy and other disorders.}, }
@article {pmid26474235, year = {2015}, author = {Bell, DS}, title = {Changes seen in gut bacteria content and distribution with obesity: causation or association?.}, journal = {Postgraduate medicine}, volume = {127}, number = {8}, pages = {863-868}, doi = {10.1080/00325481.2015.1098519}, pmid = {26474235}, issn = {1941-9260}, mesh = {Animals ; Bacteroidetes/growth &amp; development ; Bile Acids and Salts/metabolism ; *Diet, Western ; Firmicutes/growth &amp; development ; Gastric Bypass ; Gastrointestinal Tract/metabolism/*microbiology ; Humans ; Inflammation/metabolism ; Microbiota/*physiology ; Obesity/metabolism/*microbiology ; Receptors, Cytoplasmic and Nuclear/metabolism ; Weight Loss/physiology ; }, abstract = {OBJECTIVE: In the microbiota of both obese animals and humans there is an increased ratio of the gram positive Firmicutes to the gram negative Bacteroidetes (the obesity pattern). To assess if altering this ratio in animals and humans would prevent obesity or reduce body weight in the obese subject this review was preformed.<br><br>METHODS: A survey of all the available English language literature utilizing Medline on this topic was obtained and critically reviewed. The key words that were utilized were gut microbiota, diet and obesity.<br><br>RESULTS: In both humans and animals changes in diet, particularly the utilization of the high fat, high calorie Western diet, utilization of artificial sweeteners and disruption of the diurnal rhythm will quickly change the microbiota from a thin to an obese pattern. In animals, the transfer of an obese microbiota to germ free animals and thin animals results in obesity and the introduction of a lean microbiota will result in weight loss in obese animals. However, in humans similar changes in the gut microbiota induced with probiotics and prebiotics have not been shown to result in weight loss. In both animals and humans the most dramatic changes in the gut microbiota occur following weight loss resulting from a gastric bypass where there is a restoration to a normal Firmicutes to Bacteroidetes ratio. These changes could either be due to the dramatic change in the composition of the diet which occurs following this surgery or due to down-regulation of the Farnesoid X Receptor which causes a decrease in bile acid production and an elevation of the gut pH which in turn allows the regrowth of bacteria associated with weight loss which were previously unable to grow in the acidic intestinal environment caused by excess production of bile acids.<br><br>CONCLUSION: In both humans and animals there are characteristic changes in the gut microbiota associated with obesity. In animals but not in humans altering the microbiota can result in weight loss and weight gain which does not occur in humans. This suggests that in humans the changes in gut microbiota are an association with rather than the cause of obesity.}, }
@article {pmid26473796, year = {2016}, author = {Mishra, B and Chandra, A and Gejje, S and Noushif, M and Upadhyay, DN and Mishra, N}, title = {Free Antropyloric Valve Flap for End-Stage Fecal Incontinence as a Substitute to Permanent Colostomy.}, journal = {Journal of reconstructive microsurgery}, volume = {32}, number = {3}, pages = {215-221}, doi = {10.1055/s-0035-1565249}, pmid = {26473796}, issn = {1098-8947}, mesh = {Adenocarcinoma/surgery ; Anal Canal/surgery ; Anastomosis, Surgical ; Colostomy ; Fecal Incontinence/etiology/*surgery ; Free Tissue Flaps/*blood supply ; Humans ; Male ; Manometry ; Middle Aged ; Pancreaticoduodenectomy ; Pylorus/blood supply/innervation/*transplantation ; Quality of Life ; Rectal Neoplasms/surgery ; }, abstract = {BACKGROUND: Surgical removal of the anal canal and sphincter for carcinoma results in end-stage fecal incontinence (ESFI) and requires a permanent colostomy resulting in significant impact on quality of life. Presently, there are limited options for EFSI. The successful use of pedicled antropyloric valve (APV) based on left gastroepiploic artery as an alternative to permanent colostomy has previously been described. It is based on a long omental pedicle which at times is risky and is difficult to perform. A free APV flap could be the only solution in such cases. We assessed the vascular anatomy for the technical feasibility of a free APV flap, and report the first ever clinical application of free APV flap.<br><br>METHODS: Bench dissection of 10 pancreaticoduodenectomy specimens was done to delineate the vessels of APV flap. It showed the consistent presence of right gastroepiploic and infrapyloric vessels in all specimens with sufficient diameters. After the technical feasibility, a free APV Flap transposition to perineum was done in a patient, where pedicled transposition was not feasible.<br><br>RESULTS: The free APV flap with vagus nerve branch was harvested without extensive dissection along the greater curvature of stomach. A tension free anastomosis was achieved between the epiploic and left colic vessels. The flap survived well and had a definite tone on digital examination. It was evaluated by radiological and manometric methods.<br><br>CONCLUSIONS: APV flap for EFSI can be done as a free flap with distinct advantages and it has the potential of becoming popular options for EFSI.}, }
@article {pmid26470932, year = {2015}, author = {Çetinkaya, &#xdc; and Dursun, &#x130; and Kuk, S and Şahin, &#x130; and Yazar, S}, title = {[Cryptosporidium parvum Gastroenteritis in a Patient with Renal Transplantation].}, journal = {Turkiye parazitolojii dergisi}, volume = {39}, number = {3}, pages = {231-233}, doi = {10.5152/tpd.2015.3886}, pmid = {26470932}, issn = {2146-3077}, mesh = {Child ; Coloring Agents ; Cryptosporidiosis/*parasitology ; Cryptosporidium parvum/genetics/immunology/*isolation &amp; purification ; Diarrhea/*parasitology ; Enzyme-Linked Immunosorbent Assay/veterinary ; Feces/parasitology ; Gastroenteritis/*parasitology ; Humans ; *Kidney Transplantation ; Male ; Polymerase Chain Reaction ; Rosaniline Dyes ; Sequence Analysis, DNA ; }, abstract = {In this study, a case who starting abundant watery diarrhea on the 14th day of renal transplantation is presented. Stool sample was analyzed for Cryptosporidium spp. by carbol fuchsin staining method, copro-ELISA and nested polimeraze chain reaction (PCR). From sample found positive by Carbol-fuchsin staining method and Copro-ELISA, DNA sequence analysis was performed, gel-purified from amplicon obtained by nested PCR. As a result of DNA sequence analysis was determined to be Cryptosporidium parvum. Although C. parvum is a rare causative agent of gastroenteritis it can be cause serious clinical diarrhea solid organ transplantation patient. As a result, also C.parvum must be considered as a causative agent of diarrhea occurring after organ transplantation.}, }
@article {pmid26468081, year = {2015}, author = {Pozhitkov, AE and Leroux, BG and Randolph, TW and Beikler, T and Flemmig, TF and Noble, PA}, title = {Towards microbiome transplant as a therapy for periodontitis: an exploratory study of periodontitis microbial signature contrasted by oral health, caries and edentulism.}, journal = {BMC oral health}, volume = {15}, number = {}, pages = {125}, pmid = {26468081}, issn = {1472-6831}, support = {T90 DE021984/DE/NIDCR NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification ; Biofilms ; Dental Caries/microbiology/therapy ; Dental Plaque/microbiology ; Gingiva/microbiology ; Humans ; *Microbiota ; Mouth/microbiology ; *Periodontitis/microbiology/therapy ; *Transplantation ; }, abstract = {BACKGROUND: Conventional periodontal therapy aims at controlling supra- and subgingival biofilms. Although periodontal therapy was shown to improve periodontal health, it does not completely arrest the disease. Almost all subjects compliant with periodontal maintenance continue to experience progressive clinical attachment loss and a fraction of them loses teeth. An oral microbial transplant may be a new alternative for treating periodontitis (inspired by fecal transplant). First, it must be established that microbiomes of oral health and periodontitis are distinct. In that case, the health-associated microbiome could be introduced into the oral cavity of periodontitis patients. This relates to the goals of our study: (i) to assess if microbial communities of the entire oral cavity of subjects with periodontitis were different from or oral health contrasted by microbiotas of caries and edentulism patients; (ii) to test in vitro if safe concentration of sodium hypochlorite could be used for initial eradication of the original oral microbiota followed by a safe neutralization of the hypochlorite prior transplantation.<br><br>METHODS: Sixteen systemically healthy white adults with clinical signs of one of the following oral conditions were enrolled: periodontitis, established caries, edentulism, and oral health. Oral biofilm samples were collected from sub- and supra-gingival sites, and oral mucosae. DNA was extracted and 16S rRNA genes were amplified. Amplicons from the same patient were pooled, sequenced and quantified. Volunteer's oral plaque was treated with saline, 16&#xa0;mM NaOCl and NaOCl neutralized by ascorbate buffer followed by plating on blood agar.<br><br>RESULTS: Ordination plots of rRNA gene abundances revealed distinct groupings for the oral microbiomes of subjects with periodontitis, edentulism, or oral health. The oral microbiome in subjects with periodontitis showed the greatest diversity harboring 29 bacterial species at significantly higher abundance compared to subjects with the other assessed conditions. Healthy subjects had significantly higher abundance in 10 microbial species compared to the other conditions. NaOCl showed strong antimicrobial properties; nontoxic ascorbate was capable of neutralizing the hypochlorite.<br><br>CONCLUSIONS: Distinct oral microbial signatures were found in subjects with periodontitis, edentulism, or oral health. This finding opens up a potential for a new therapy, whereby a health-related entire oral microbial community would be transplanted to the diseased patient.}, }
@article {pmid26460906, year = {2016}, author = {Echenique, IA and Stosor, V and Gallon, L and Kaufman, D and Qi, C and Zembower, TR}, title = {Prolonged norovirus infection after pancreas transplantation: a case report and review of chronic norovirus.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {18}, number = {1}, pages = {98-104}, doi = {10.1111/tid.12472}, pmid = {26460906}, issn = {1399-3062}, mesh = {Caliciviridae Infections/complications/*virology ; Chronic Disease ; Female ; Gastroenteritis/complications/*virology ; Graft Rejection ; Humans ; Immunocompromised Host ; Immunosuppression Therapy/adverse effects ; Kidney Failure, Chronic/*complications ; Middle Aged ; Norovirus/genetics/*isolation &amp; purification ; Pancreas Transplantation/*adverse effects ; }, abstract = {Norovirus is a major cause of self-limited gastroenteritis worldwide. Prevention and treatment are thwarted by rapid viral evolution, and thus supportive care remains the mainstay of therapy. Chronic infection in immunocompromised hosts is increasingly described. We report a case of norovirus infection lasting 2543 days in a pancreas transplant recipient. Serial fecal specimens were obtained, from which a map of genetic relatedness was derived. The clinical course was complicated by renal failure that progressed to end-stage renal disease. Minimization of immunosuppression was associated with resolution of the infection. Subsequently, the patient experienced a suspected allograft rejection that did not compromise pancreas function. The patient later underwent living-related renal transplantation without recurrence of enteritis.}, }
@article {pmid26459447, year = {2016}, author = {Gérard, P}, title = {Gut microbiota and obesity.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {73}, number = {1}, pages = {147-162}, pmid = {26459447}, issn = {1420-9071}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/pharmacology ; Appetite Regulation ; Bacteria/drug effects/metabolism ; Dietary Fiber/therapeutic use ; Dietary Supplements/microbiology ; Fermentation ; *Gastrointestinal Microbiome/drug effects ; Humans ; Obesity/metabolism/*microbiology/physiopathology/therapy ; Prebiotics/analysis ; Probiotics/therapeutic use ; }, abstract = {The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity.}, }
@article {pmid26457381, year = {2016}, author = {Ince, MN and Blazar, BR and Edmond, MB and Tricot, G and Wannemuehler, MJ}, title = {Understanding Luminal Microorganisms and Their Potential Effectiveness in Treating Intestinal Inflammation.}, journal = {Inflammatory bowel diseases}, volume = {22}, number = {1}, pages = {194-201}, pmid = {26457381}, issn = {1536-4844}, support = {R01 HL56067/HL/NHLBI NIH HHS/United States ; R01 HL118979/HL/NHLBI NIH HHS/United States ; R01 AI 34495/AI/NIAID NIH HHS/United States ; R01 AI034495/AI/NIAID NIH HHS/United States ; R56 AI116715/AI/NIAID NIH HHS/United States ; R01 HL056067/HL/NHLBI NIH HHS/United States ; R01 AI112613/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; Inflammation/*therapy ; Intestines/immunology/*microbiology ; *Microbiota ; }, abstract = {The human intestine contains 10[14] bacteria, which outnumber the mammalian cells 10-fold. Certain other commensal or infectious agents, like helminthic parasites, become members of this microbial ecosystem, especially in populations living under less hygienic conditions. Intestinal microbes, also called the microbiome or microbiota, shape the host immune reactivity to self and nonself throughout life. Changes in microbiome composition may impair the maturation of immune regulatory pathways and predispose the host to develop various forms of inflammatory disorders, like Crohn's disease or ulcerative colitis. The microbiome is also critical to successful transplantation of organs or grafts. After allogeneic hematopoietic stem cell transplantation, when the new donor cells, such as T lymphocytes learn to discriminate "the new self from nonself" in the transplant recipient, they need healthy microbiota-derived signals to preserve the immune homeostasis. Restoring microbiota through intestinal delivery of bacterial strains, helminths, fecal microbiota transplantation, or stool substitutes have the potential to improve and correct aberrant immune reactivity in various disorders.}, }
@article {pmid26456940, year = {2015}, author = {Runtsch, MC and Hu, R and Alexander, M and Wallace, J and Kagele, D and Petersen, C and Valentine, JF and Welker, NC and Bronner, MP and Chen, X and Smith, DP and Ajami, NJ and Petrosino, JF and Round, JL and O'Connell, RM}, title = {MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis.}, journal = {Oncotarget}, volume = {6}, number = {30}, pages = {28556-28572}, pmid = {26456940}, issn = {1949-2553}, mesh = {Animals ; Colitis/chemically induced/genetics/*immunology/metabolism/microbiology/pathology/prevention &amp; control ; Colon/*immunology/metabolism/microbiology/pathology ; *Dextran Sulfate ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/immunology ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Host-Pathogen Interactions ; *Immunity, Mucosal ; Inflammation Mediators/immunology/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs/genetics/*immunology/metabolism ; Phenotype ; Signal Transduction ; T-Lymphocyte Subsets/immunology/metabolism ; Time Factors ; }, abstract = {Host-microbial interactions within the mammalian intestines must be properly regulated in order to promote host health and limit disease. Because the microbiota provide constant immunological signals to intestinal tissues, a variety of regulatory mechanisms have evolved to ensure proper immune responses to maintain homeostasis. However, many of the genes that comprise these regulatory pathways, including immune-modulating microRNAs (miRNAs), have not yet been identified or studied in the context of intestinal homeostasis. Here, we investigated the role of microRNA-146a (miR-146a) in regulating intestinal immunity and barrier function and found that this miRNA is expressed in a variety of gut tissues in adult mice. By comparing intestinal gene expression in WT and miR-146a-/- mice, we demonstrate that miR-146a represses a subset of gut barrier and inflammatory genes all within a network of immune-related signaling pathways. We also found that miR-146a restricts the expansion of intestinal T cell populations, including Th17, Tregs, and Tfh cells. GC B cells, Tfh ICOS expression, and the production of luminal IgA were also reduced by miR-146a in the gut. Consistent with an enhanced intestinal barrier, we found that miR-146a-/- mice are resistant to DSS-induced colitis, a model of Ulcerative Colitis (UC), and this correlated with elevated colonic miR-146a expression in human UC patients. Taken together, our data describe a role for miR-146a in constraining intestinal barrier function, a process that alters gut homeostasis and enhances at least some forms of intestinal disease in mice.}, }
@article {pmid26455382, year = {2016}, author = {Mills, JP and Talati, NJ and Alby, K and Han, JH}, title = {The Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Colonization and Infection among Long-Term Acute Care Hospital Residents.}, journal = {Infection control and hospital epidemiology}, volume = {37}, number = {1}, pages = {55-60}, pmid = {26455382}, issn = {1559-6834}, support = {K01 AI103028/AI/NIAID NIH HHS/United States ; FOA#CK11-001/CK/NCEZID CDC HHS/United States ; K01-AI103028/AI/NIAID NIH HHS/United States ; }, mesh = {Aged ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Carbapenems/*pharmacology ; Carrier State/*epidemiology/microbiology ; Case-Control Studies ; *Drug Resistance, Bacterial ; Fecal Incontinence/epidemiology ; Female ; Hospitals/*statistics &amp; numerical data ; Humans ; Klebsiella Infections/*epidemiology/microbiology ; Klebsiella pneumoniae/*drug effects ; Male ; Meropenem ; Metronidazole/therapeutic use ; Middle Aged ; Organ Transplantation ; Respiration, Artificial ; Risk Factors ; Stem Cell Transplantation ; Thienamycins/therapeutic use ; Time Factors ; Vancomycin/therapeutic use ; }, abstract = {OBJECTIVE An improved understanding of carbapenem-resistant Klebsiella pneumoniae (CRKP) in long-term acute care hospitals (LTACHs) is needed. The objective of this study was to assess risk factors for colonization or infection with CRKP in LTACH residents. METHODS A case-control study was performed at a university-affiliated LTACH from 2008 to 2013. Cases were defined as all patients with clinical cultures positive for CRKP and controls were those with clinical cultures positive for carbapenem-susceptible K. pneumoniae (CSKP). A multivariate model was developed to identify risk factors for CRKP infection or colonization. RESULTS A total of 222 patients were identified with K. pneumoniae clinical cultures during the study period; 99 (45%) were case patients and 123 (55%) were control patients. Our multivariate analysis identified factors associated with a significant risk for CRKP colonization or infection: solid organ or stem cell transplantation (OR, 5.05; 95% CI, 1.23-20.8; P=.03), mechanical ventilation (OR, 2.56; 95% CI, 1.24-5.28; P=.01), fecal incontinence (OR, 5.78; 95% CI, 1.52-22.0; P=.01), and exposure in the prior 30 days to meropenem (OR, 3.55; 95% CI, 1.04-12.1; P=.04), vancomycin (OR, 2.94; 95% CI, 1.18-7.32; P=.02), and metronidazole (OR, 4.22; 95% CI, 1.28-14.0; P=.02). CONCLUSIONS Rates of colonization and infection with CRKP were high in the LTACH setting, with nearly half of K. pneumoniae cultures demonstrating carbapenem resistance. Further studies are needed on interventions to limit the emergence of CRKP in LTACHs, including targeted surveillance screening of high-risk patients and effective antibiotic stewardship measures. Infect. Control Hosp. Epidemiol. 2015;37(1):55-60.}, }
@article {pmid26454536, year = {2015}, author = {Lellek, H and Franke, GC and Ruckert, C and Wolters, M and Wolschke, C and Christner, M and Büttner, H and Alawi, M and Kröger, N and Rohde, H}, title = {Emergence of daptomycin non-susceptibility in colonizing vancomycin-resistant Enterococcus faecium isolates during daptomycin therapy.}, journal = {International journal of medical microbiology : IJMM}, volume = {305}, number = {8}, pages = {902-909}, doi = {10.1016/j.ijmm.2015.09.005}, pmid = {26454536}, issn = {1618-0607}, mesh = {Anti-Bacterial Agents/*pharmacology/therapeutic use ; DNA, Bacterial/chemistry/genetics ; Daptomycin/*pharmacology/therapeutic use ; *Drug Tolerance ; Enterococcus faecium/*drug effects/isolation &amp; purification ; Feces/microbiology ; Genome, Bacterial ; Gram-Positive Bacterial Infections/microbiology ; Humans ; Microbial Sensitivity Tests ; Polymorphism, Single Nucleotide ; Vancomycin-Resistant Enterococci/*drug effects/isolation &amp; purification ; }, abstract = {Infections due to vancomycin-resistant enterococci (VRE) are of significant importance in high-risk populations, and daptomycin is a bactericidal antibiotic to treat multidrug-resistant VRE in these patients. The emergence of daptomycin non-susceptibility invasive VRE during daptomycin therapy is a major clinical issue. Here the hypothesis was tested that systemic daptomycin therapy also induces the emergence of daptomycin non-susceptible (DNS-) isolates in colonizing VRE populations. 11 vancomycin-resistant Enterococcus faecium strain pairs recovered from rectal swabs were available for analysis. All initial isolates exhibited daptomycin MICs within the wild type MIC distribution of E. faecium (MIC≤4 mg/L). In follow-up isolates from five patients a 4-16-fold daptomycin MIC increase was detected. All patients carrying DNS-VRE received daptomycin (14-28 days) at 4 mg/kg body weight, while two patients in whom no DNS-VRE emerged were only treated with daptomycin for 1 and 4 days, respectively. Comparative whole genome sequencing identified DNS-VRE-specific single nucleotide polymorphisms (SNP), including mutations in cardiolipin synthase (Cls), and additional SNPs in independent genes potentially relevant for the DNS phenotype. Mutations within cls were also identified in three additional, colonizing DNS-VRE. Of these, at least one strain was transmitted within the hospital. In none of the VRE isolates tested, pre-existing or de novo mutations in the liaFSR operon were detected. This is the first report documenting the emergence of DNS-VRE in colonizing strains during daptomycin treatment, putting the patient at risk for subsequent DNS-VRE infections and priming the spread of DNS-VRE within the hospital environment.}, }
@article {pmid26454211, year = {2016}, author = {Harrell, CS and Gillespie, CF and Neigh, GN}, title = {Energetic stress: The reciprocal relationship between energy availability and the stress response.}, journal = {Physiology &amp; behavior}, volume = {166}, number = {}, pages = {43-55}, pmid = {26454211}, issn = {1873-507X}, support = {K18 MH105098/MH/NIMH NIH HHS/United States ; R01 MH099211/MH/NIMH NIH HHS/United States ; R01 MH110364/MH/NIMH NIH HHS/United States ; T32 GM008169/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Energy Metabolism/*physiology ; Glucocorticoids/metabolism ; Humans ; Metabolic Diseases/*complications ; Neurosecretory Systems/*physiopathology ; Stress, Psychological/*complications/physiopathology ; }, abstract = {The worldwide epidemic of metabolic syndromes and the recognized burden of mental health disorders have driven increased research into the relationship between the two. A maladaptive stress response is implicated in both mental health disorders and metabolic disorders, implicating the hypothalamic-pituitary-adrenal (HPA) axis as a key mediator of this relationship. This review explores how an altered energetic state, such as hyper- or hypoglycemia, as may be manifested in obesity or diabetes, affects the stress response and the HPA axis in particular. We propose that changes in energetic state or energetic demands can result in "energetic stress" that can, if prolonged, lead to a dysfunctional stress response. In this review, we summarize the role of the hypothalamus in modulating energy homeostasis and then briefly discuss the relationship between metabolism and stress-induced activation of the HPA axis. Next, we examine seven mechanisms whereby energetic stress interacts with neuroendocrine stress response systems, including by glucocorticoid signaling both within and beyond the HPA axis; by nutrient-induced changes in glucocorticoid signaling; by impacting the sympathetic nervous system; through changes in other neuroendocrine factors; by inducing inflammatory changes; and by altering the gut-brain axis. Recognizing these effects of energetic stress can drive novel therapies and prevention strategies for mental health disorders, including dietary intervention, probiotics, and even fecal transplant.}, }
@article {pmid26452390, year = {2015}, author = {Serban, DE}, title = {Microbiota in Inflammatory Bowel Disease Pathogenesis and Therapy: Is It All About Diet?.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {30}, number = {6}, pages = {760-779}, doi = {10.1177/0884533615606898}, pmid = {26452390}, issn = {1941-2452}, mesh = {*Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology/*therapy ; *Prebiotics ; Probiotics/*therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD), including ulcerative colitis, Crohn's disease, and unclassified IBD, continues to cause significant morbidity. While its incidence is increasing, no clear etiology and no cure have yet been discovered. Recent findings suggest that IBD may have a multifactorial etiology, where complex interactions between genetics, epigenetics, environmental factors (including diet but also infections, antibiotics, and sanitation), and host immune system lead to abnormal immune responses and chronic inflammation. Over the past years, the role of altered gut microbiota (in both composition and function) in IBD pathogenesis has emerged as an outstanding area of interest. According to new findings, gut dysbiosis may appear as a key element in initiation of inflammation in IBD and its complications. Moreover, complex metagenomic studies provide possibilities to distinguish between IBD types and appreciate severity and prognosis of the disease, as well as response to therapy. This review provides an updated knowledge of recent findings linking altered bacterial composition and functions, viruses, and fungi to IBD pathogenesis. It also highlights the complex genetic, epigenetic, immune, and microbial interactions in relation to environmental factors (including diet). We overview the actual options to manipulate the altered microbiota, such as modified diet, probiotics, prebiotics, synbiotics, antibiotics, and fecal transplantation. Future possible therapies are also included. Targeting altered microbiota could be the next therapeutic personalized approach, but more research and well-designed comparative prospective studies are required to formulate adequate directions for prevention and therapy.}, }
@article {pmid26447968, year = {2015}, author = {Brandt, LJ}, title = {Fecal Microbiota Transplant: Respice, Adspice, Prospice.}, journal = {Journal of clinical gastroenterology}, volume = {49 Suppl 1}, number = {}, pages = {S65-8}, doi = {10.1097/MCG.0000000000000346}, pmid = {26447968}, issn = {1539-2031}, mesh = {Clostridioides difficile ; Dysbiosis/microbiology/therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*trends ; Feces/microbiology ; Humans ; }, abstract = {Respice, Adspice, Prospice, look to the past, look to the present, look to the future, is one of life's valuable axioms; for it is only if one knows where one has been can one intelligently prepare for the future. I have used this approach here to review fecal microbiota transplant (FMT). First used in fourth-century China to treat an assortment of gastrointestinal (GI) symptoms, today FMT is primarily used for recurrent Clostridium difficile infection (RCDI). In the future, however, it is likely that microbiotic therapy will be extended beyond treatment of RCDI. Early on, fresh feces from patient-identified donors was used and administered by several routes. FMT cure rates for RCDI remain approximately 82% and 91% when fresh stool is given by the upper GI and lower GI routes, respectively, but now we are moving in the direction of using carefully vetted volunteers whose stool is processed into a variety of formulations including lyophilized material and even capsules. It is very likely that an array of products derived from feces or based on specific microbiotic profiles and commercially prepared in a controlled environment will be available to restore eubiosis to a dysbiotic intestinal microbial community, and thereby correct a variety of GI and non-GI disorders. We are witnessing a paradigm shift in therapeutics. Previously, bacteria were thought of only as potential pathogens, whereas now we appreciate that a diverse community of bacteria is crucial to the health of the host. We are now learning that to restore such diversity once it has been interrupted can result in miraculous cure. The future of microbiotic therapy is bright.}, }
@article {pmid26447957, year = {2015}, author = {Bakker, GJ and Zhao, J and Herrema, H and Nieuwdorp, M}, title = {Gut Microbiota and Energy Expenditure in Health and Obesity.}, journal = {Journal of clinical gastroenterology}, volume = {49 Suppl 1}, number = {}, pages = {S13-9}, doi = {10.1097/MCG.0000000000000363}, pmid = {26447957}, issn = {1539-2031}, mesh = {Animals ; Bacterial Translocation ; Diabetes Mellitus, Type 2/microbiology ; *Energy Metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammation/microbiology ; Insulin Resistance ; Mice ; Obesity/*microbiology ; }, abstract = {The contribution of intestinal bacterial strains (gut microbiota) to the development of obesity and obesity-related disorders is increasingly recognized as a potential diagnostic and pharmacologic target. Alterations in the intestinal bacterial composition have been associated with presence of chronic low-grade inflammation, a known feature of insulin resistance and type 2 diabetes mellitus. However, causality still needs to be proven. Fecal transplantation studies in germ-free mice have provided crucial insight into the causality of gut microbiota in development of obesity and obesity-related disorders. Moreover, fecal transplantation studies in conjunction with fecal sampling in prospectively followed cohorts will help identify causally involved intestinal bacterial strains in human obesity. Results from these studies will lead to characterization of novel diagnostic markers as well as therapeutic strategies that aim to treat obesity and obesity-related disorders.}, }
@article {pmid26439370, year = {2015}, author = {Hirayama, Y and Iinuma, Y and Yokoyama, N and Otani, T and Masui, D and Komatsuzaki, N and Higashidate, N and Tsuruhisa, S and Iida, H and Nakaya, K and Naito, S and Nitta, K and Yagi, M}, title = {Near-infrared fluorescence cholangiography with indocyanine green for biliary atresia. Real-time imaging during the Kasai procedure: a pilot study.}, journal = {Pediatric surgery international}, volume = {31}, number = {12}, pages = {1177-1182}, pmid = {26439370}, issn = {1437-9813}, mesh = {Bile Ducts/surgery ; Biliary Atresia/*surgery ; *Cholangiography ; Coloring Agents ; Female ; Fluorescence ; Humans ; *Indocyanine Green ; Infant ; Male ; Pilot Projects ; Portoenterostomy, Hepatic/*methods ; *Radiology, Interventional ; }, abstract = {INTRODUCTION: Hepatoportoenterostomy (HPE) with the Kasai procedure is the treatment of choice for biliary atresia (BA) as the initial surgery. However, the appropriate level of dissection level of the fibrous cone (FC) of the porta hepatis (PH) is frequently unclear, and the procedure sometimes results in unsuccessful outcomes. Recently, indocyanine green near-infrared fluorescence imaging (ICG-FCG) has been developed as a form of real-time cholangiography.<br><br>METHODS: We applied this technique in five patients with BA to visualize the biliary flow at the PH intraoperatively. ICG was injected intravenously the day before surgery as the liver function test, and the liver was observed with a near-infrared camera system during the operation while the patient's feces was also observed.<br><br>RESULTS: In all patients, the whole liver fluoresced diffusely with ICG-containing stagnant bile, whereas no extrahepatic structures fluoresced. The findings of the ICG fluorescence pattern of the PH after dissection of the FC were classified into three types: spotty fluorescence, one patient; diffuse weak fluorescence, three patients; and diffuse strong fluorescence, one patient. In all five patients, the feces evacuated after HPE showed distinct fluorescent spots, although that obtained before surgery showed no fluorescence. One patient with diffuse strong fluorescence who did not achieve JF underwent living related liver transplantation six months after the initial HPE procedure. Four patients, including three cases involving diffuse weak fluorescence and one case involving spotty fluorescence showed weak fluorescence compared to that of the surrounding liver surface.<br><br>CONCLUSION: We were able to detect the presence of bile excretion at the time of HPE intraoperatively and successfully evaluated the extent of bile excretion using this new technique. Furthermore, the ICG-FCG findings may provide information leading to a new classification and potentially function as an indicator predicting the clinical outcomes after HPE.}, }
@article {pmid26433619, year = {2016}, author = {Sokol, H and Galperine, T and Kapel, N and Bourlioux, P and Seksik, P and Barbut, F and Scanzi, J and Chast, F and Batista, R and Joly, F and Joly, AC and Collignon, A and Guery, B and Beaugerie, L and , }, title = {Faecal microbiota transplantation in recurrent Clostridium difficile infection: Recommendations from the French Group of Faecal microbiota Transplantation.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {48}, number = {3}, pages = {242-247}, doi = {10.1016/j.dld.2015.08.017}, pmid = {26433619}, issn = {1878-3562}, mesh = {*Clostridioides difficile ; Clostridium Infections/therapy ; Donor Selection ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/*methods ; France ; Gastroenterology ; Humans ; Patient Selection ; Recurrence ; }, abstract = {Faecal microbiota transplantation is effective for treating recurrent forms of Clostridium difficile infection and its use in this indication is recommended in the most recent European and North American guidelines. In this context, faecal microbiota transplantation is beginning to be performed in France in clinical practice, while the rules governing this procedure have been defined in France only for clinical trials. To unify, secure, and evaluate practice in this field in France, the French Group of Faecal microbiota Transplantation (FGFT) was created in October 2014 with the support of the French National Society of Gastroenterology, the French Infectious Disease Society, and the National Academy of Pharmacy. We present here the deliberations of this group regarding the use of faecal microbiota transplantation for recurrent Clostridium difficile infection. The issues addressed are the indications, therapeutic sequence, delivery procedures, donor selection, methods and conditions of specimen preparation, and traceability.}, }
@article {pmid26429302, year = {2015}, author = {Saint-Georges-Chaumet, Y and Attaf, D and Pelletier, E and Edeas, M}, title = {Targeting microbiota-mitochondria inter-talk: Microbiota control mitochondria metabolism.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {61}, number = {4}, pages = {121-124}, pmid = {26429302}, issn = {1165-158X}, mesh = {Fatty Acids/metabolism ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Hydrogen Sulfide/metabolism ; Mitochondria/*metabolism ; Nitric Oxide/metabolism ; Oxidation-Reduction ; Oxidative Stress/*physiology ; Reactive Oxygen Species/metabolism ; }, abstract = {Our aim is to highlight the subtle relationship that exists between microbiota and mitochondria. Microbiota targets mitochondria by modulating the Reactive Oxygen Species (ROS) production and the mitochondrial activity through interactions with toxins, proteins or other metabolites released by gut microbiota. The intriguing relationship that exists between mitochondria and microbiota is strengthened by the probable prokaryotic origin of mitochondria. Emerging data implicates a role for ROS, nitric oxide, Short Chain Fatty Acids and hydrogen sulfide in the cross-talk between microbiota - mitochondria and REDOX signaling. Several studies have shown that microbiota act and modulate mitochondrial activity, and use it as a relay to strengthen host-microbiotal interaction. This modulation depends on the gut bacterial strain quality and diversity to increase its pathogenic versus beneficial effects. Furthermore, based on conclusions from new studies, it is possible that microbiota can directly interact with the host cell gene expression by favoring bacterial and mitochondrial DNA insertion in the nuclear genome. The emerging knowledge of mitochondria-microbiota interaction may be of great importance to better understand the mechanism of mitochondrial and metabolic diseases, and the syndromes associated with change in quality and quantity of microbiotal species. We suggest that microbiota via mitochondrial modulation influence cell homeostasis and metabolism. The challenge will be to find strategies to modulate the quality and diversity of microbiota rather than acting on microbiota metabolites and microbiota related factors. The medicine of tomorrow will be completely personalized. Firstly there will be a test to show the quality, quantity and diversity of microbiota, and secondly a preventive or therapeutic strategy will be administrated (probiotics, diet, prodrug or fecal transplantation). The era of digital medicine is here.}, }
@article {pmid26424474, year = {2016}, author = {Kajbafzadeh, AM and Kajbafzadeh, M and Sabetkish, S and Sabetkish, N and Tavangar, SM}, title = {Tissue-Engineered External Anal Sphincter Using Autologous Myogenic Satellite Cells and Extracellular Matrix: Functional and Histological Studies.}, journal = {Annals of biomedical engineering}, volume = {44}, number = {5}, pages = {1773-1784}, doi = {10.1007/s10439-015-1468-3}, pmid = {26424474}, issn = {1573-9686}, mesh = {*Anal Canal/metabolism/pathology/surgery ; Animals ; *Bioprosthesis ; Disease Models, Animal ; *Extracellular Matrix/pathology/transplantation ; *Fecal Incontinence/metabolism/pathology/surgery ; Female ; Male ; Rabbits ; *Satellite Cells, Skeletal Muscle/metabolism/pathology ; Tissue Engineering/*methods ; }, abstract = {The aim of the present study was to demonstrate the regaining histological characteristics of bioengineered external anal sphincters (EAS) in rabbit fecal incontinence model. The EAS of 16 rabbits were resected and decellularized. The decellularized scaffolds were transplanted to the terminal rectum following a period of 6 months of fecal incontinency (5 days after sterilization). The rabbits were divided into two groups: in group 1 (n = 8), myogenic satellite cells were injected into the transplanted sphincters. In group 2 (n = 8), the transplanted scaffolds remained in situ without cellular injection. The histological evaluation was performed with desmin, myosin, smooth muscle actin, CD31, and CD34 at 3-month intervals. The rabbits were followed for 2 years. Electromyography (EMG) with needle and electrical stimulation, pudendal and muscle electrical stimulation were also performed after 2 years of transplantation. At the time of biopsy, no evidence of inflammation or rejection was observed and the transplanted EAS appeared histologically and anatomically normal. The immunohistochemistry staining validated that the histological features of EAS was more satisfactory in group 1 in short-term follow-up. However, no statistically significant difference was detected between two groups in long-term follow-ups (p value > 0.05). In both groups, grafted EAS contracted in response to electrical signals delivered to the muscle and the pudendal nerve. However, more signals were detected in group 1 in EMG evaluation. In conclusion, bioengineered EAS with myogenic satellite cells can gain more satisfactory histological outcomes in short-term follow-ups with better muscle electrical stimulation outcomes.}, }
@article {pmid26423670, year = {2015}, author = {Mirjalali, H and Mirhendi, H and Meamar, AR and Mohebali, M and Askari, Z and Mirsamadi, ES and Rezaeian, M}, title = {Genotyping and molecular analysis of Enterocytozoon bieneusi isolated from immunocompromised patients in Iran.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {36}, number = {}, pages = {244-249}, doi = {10.1016/j.meegid.2015.09.022}, pmid = {26423670}, issn = {1567-7257}, mesh = {AIDS-Related Opportunistic Infections/*microbiology ; Base Sequence ; DNA, Fungal/analysis/genetics ; Enterocytozoon/*genetics ; Feces/microbiology ; Female ; Genotyping Techniques ; Humans ; Immunocompromised Host ; Iran ; Male ; Microsporidiosis/*microbiology ; Molecular Sequence Data ; Molecular Typing ; Sequence Alignment ; }, abstract = {Microsporidia are known as opportunistic unicellular pathogens, particularly so in individuals with congenital or acquired immunodeficiency. Enterocytozoon bieneusi is one of the most common species infecting both immunocompromised and immunocompetent individuals. The aim of this study was to assess the distribution of E. bieneusi genotypes among immunocompromised patients in Iran. From 329 stool samples referred for parasitological analysis during 2011-2014, 14 samples from immunocompromised patients proving positive for E. bieneusi by SSU rDNA analysis were selected. Genotyping was carried out using specific primers targeting the Internal Transcribed Spacer (ITS) region. Subsequently, all samples were sequenced and results queried against the GenBank database. Moreover, sequences were subject to phylogenetic analysis. The expected amplification product was generated for all samples. Genotype D was identified in patients with HIV+/AIDS, transplant recipients, and cancer patients, while Genotype E was identified only in cancer and HIV+/AIDS patients. Phylogenetic analysis revealed that there was no relationship between genotypes and types of immunosuppression, whereas most genotype D isolates grouped with those described previously from cattle, horses, birds, and humans. E. bieneusi genotype D appears to be the most frequent genotype in immunocompromised patients, while Genotype E was observed only in HIV+/AIDS patients and cancer patients, not transplant recipients.}, }
@article {pmid26414494, year = {2015}, author = {Wexner, SD and Bleier, J}, title = {Current surgical strategies to treat fecal incontinence.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {9}, number = {12}, pages = {1577-1589}, doi = {10.1586/17474124.2015.1093417}, pmid = {26414494}, issn = {1747-4132}, mesh = {Anal Canal/*surgery ; Colostomy ; Dextrans/therapeutic use ; Electric Stimulation Therapy ; Fecal Incontinence/etiology/*surgery/therapy ; Humans ; Hyaluronic Acid/therapeutic use ; Ileostomy ; Lumbosacral Plexus ; Muscle, Skeletal/transplantation ; Prostheses and Implants ; Radiofrequency Therapy ; Tibial Nerve ; }, abstract = {Fecal incontinence is a devastating condition, vastly under-reported, and may affect up to 18% of the population. While conservative management may be efficacious in a large portion of patients, those who are refractory will likely benefit from appropriate surgical intervention. There are a wide variety of surgical approaches to fecal incontinence management, and knowledge and experience are crucial to choosing the appropriate procedure and maximizing functional outcome while minimizing risk. In this article, we provide a comprehensive description of surgical options for fecal incontinence to help the clinician identify an appropriate intervention.}, }
@article {pmid26414076, year = {2015}, author = {Borody, T and Fischer, M and Mitchell, S and Campbell, J}, title = {Fecal microbiota transplantation in gastrointestinal disease: 2015 update and the road ahead.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {9}, number = {11}, pages = {1379-1391}, doi = {10.1586/17474124.2015.1086267}, pmid = {26414076}, issn = {1747-4132}, mesh = {Animals ; Diffusion of Innovation ; *Fecal Microbiota Transplantation/adverse effects/trends ; Feces/*microbiology ; Forecasting ; Gastrointestinal Diseases/diagnosis/microbiology/*therapy ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Treatment Outcome ; }, abstract = {At its height, the Clostridium difficile infection epidemic caused approximately 7000 infections and 300 deaths per day in the USA. Fecal microbiota transplantation (FMT) has demonstrated extraordinary clinical resolution, C. difficile infection cure rates of over 90%, and low recurrence. In tandem with the rise of FMT, the gastrointestinal microbiome has emerged as a 'vital' organ armed with a wealth of microbe 'soldiers' more powerful than known antibiotics. FMTs' reputation has diffused into many new 'indications' yet these appear to be merely the tip of the iceberg when considering its potential applications. FMT as a therapeutic tool has evolved from the original format of blended donor stool and moved towards a refined product comprising a myriad of microbial components, presented aesthetically as encapsulated lyophilized powder.}, }
@article {pmid26410257, year = {2016}, author = {Mandalia, A and Ward, A and Tauxe, W and Kraft, CS and Dhere, T}, title = {Fecal transplant is as effective and safe in immunocompromised as non-immunocompromised patients for Clostridium difficile.}, journal = {International journal of colorectal disease}, volume = {31}, number = {5}, pages = {1059-1060}, doi = {10.1007/s00384-015-2396-2}, pmid = {26410257}, issn = {1432-1262}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; }, mesh = {Clostridioides difficile/*physiology ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Follow-Up Studies ; Humans ; *Immunocompromised Host ; }, }
@article {pmid26408803, year = {2016}, author = {Bamias, G and Pizarro, TT and Cominelli, F}, title = {Pathway-based approaches to the treatment of inflammatory bowel disease.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {167}, number = {1}, pages = {104-115}, pmid = {26408803}, issn = {1878-1810}, support = {P01 DK091222/DK/NIDDK NIH HHS/United States ; P30 DK097948/DK/NIDDK NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; R01 DK055812/DK/NIDDK NIH HHS/United States ; }, mesh = {Cytokines/metabolism ; Humans ; Inflammation/*metabolism ; Inflammatory Bowel Diseases/metabolism/*therapy ; Intestinal Mucosa/*metabolism ; }, abstract = {Crohn's disease and ulcerative colitis, collectively termed inflammatory bowel disease (IBD), are immunologic disorders that represent the prototypes of chronic intestinal inflammation. Their pathogenesis involves the dysregulated interaction between the intestinal microbiota and the gut-associated mucosal immune system that takes place when genetically predisposed individuals are exposed to detrimental environmental triggers. In recent years, the therapeutic dogma in IBD has shifted away from the administration of nonspecific immunosuppressives toward a pathway-based approach. In this review, we present an outlook of IBD treatment based on this new conceptual approach. Firstly, we will provide an overview of the major aspects of IBD pathogenesis with emphasis on specific pathway-based defects. Secondly, we will examine in detail the development of novel therapeutic approaches that can be used to target genetics, dysbiosis, the epithelial barrier, proinflammatory cytokines, and leukocyte trafficking. Most of these strategies are still in the developmental phase, but promising approaches include fecal microbiota transplantation as a means to correct IBD-related dysbiosis; administration of modified phosphatidylcholine to enhance the function of the intestinal mucous and tighten the defective epithelial barrier; the reduction of over-reactive proinflammatory pathways through the blockade of novel, nontumor necrosis factor inflammatory mediators via monoclonal antibodies against the common p40 chain of interleukin (IL-12) and IL-23, Janus kinase inhibitors, or antisense oligonucleotides against inhibitors of the immunosuppressive cytokine transforming growth factor-β1; and finally, inhibition of leukocyte trafficking to the gut via neutralization of the gut-specific α4β7 integrin. Availability of such diverse treatment modalities with specific pathway-based targets will increase the therapeutic options for patients with IBD.}, }
@article {pmid26403484, year = {2015}, author = {Nicholson, MR and Osgood, CL and Acra, SA and Edwards, KM}, title = {Clostridium difficile infection in the pediatric transplant patient.}, journal = {Pediatric transplantation}, volume = {19}, number = {7}, pages = {792-798}, doi = {10.1111/petr.12578}, pmid = {26403484}, issn = {1399-3046}, mesh = {Child ; *Clostridioides difficile ; Clostridium Infections/diagnosis/*etiology/therapy ; Humans ; *Organ Transplantation ; *Postoperative Complications/diagnosis/therapy ; Risk Factors ; }, abstract = {CDIs are on the rise in both hospital and community settings in adults and children. Children with cancer or a history of HSCT or SOT appear to be at higher risk for primary disease, recurrent disease, and severe outcomes when compared to children with other comorbidities. The reasons for this are not clear and no studies to date have analyzed risk factors for CDI in pediatric transplant patients. Colonization rates in children with cancer and a transplant history are also high. Determining which children are colonized with Clostridium difficile and symptomatic from another source vs. symptomatic from CDI is difficult and a clinical conundrum for the transplant physician. The use of fecal transplantation for severe or rCDI is likely safe and effective in the immunosuppressed pediatric cancer or transplant patient, but this will need to be more thoroughly studied in this patient population.}, }
@article {pmid26400519, year = {2015}, author = {Daloiso, V and Minacori, R and Refolo, P and Sacchini, D and Craxì, L and Gasbarrini, A and Spagnolo, AG}, title = {Ethical aspects of Fecal Microbiota Transplantation (FMT).}, journal = {European review for medical and pharmacological sciences}, volume = {19}, number = {17}, pages = {3173-3180}, pmid = {26400519}, issn = {2284-0729}, mesh = {Biological Therapy/*methods ; Fecal Microbiota Transplantation/*ethics ; Humans ; Tissue Donors ; }, abstract = {The importance of human microbiota in preserving human organism healthy is nowadays well acknowledged. The alteration of the microbiota can be the consequence of a persistent use of antibiotics or immunosuppressive medications or abdominal irradiation or surgery, wrong diet, or can be caused by surgery or anatomical condition. These alterations can cause many infections and diseases that today can be treated with Fecal Microbiota Transplantation (FMT), also called Bacteriotherapy, that is the administration of a fecal solution from a donor into the intestinal tract of a recipient. Although to date, FMT appears to be safe and without serious adverse effects, there are some ethical issues that are worthy to be investigated. The aim of this article is to highlight these issues in order to give some notes for a better implementation of this particular clinical practice.}, }
@article {pmid26397161, year = {2015}, author = {Borody, TJ and Connelly, N and Mitchell, SW}, title = {Fecal microbiota transplantation in gastrointestinal diseases: what practicing physicians should know.}, journal = {Polskie Archiwum Medycyny Wewnetrznej}, volume = {125}, number = {11}, pages = {852-858}, doi = {10.20452/pamw.3166}, pmid = {26397161}, mesh = {Biological Therapy/*methods ; Clinical Competence ; Clostridium Infections/microbiology/*therapy ; Developed Countries ; Disease Management ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Humans ; Poland ; }, abstract = {Clostridium difficile infection (CDI) is one of the most commonly reported nosocomial pathogens in the United States and Europe, with recent CDI-associated mortality in the United States approaching 30 000 deaths annually. Antibiotics remain the preferred treatment for CDI; however, a minority of patients experience numerous relapses and are treated with restoration of the bowel microbiota, termed fecal microbiota transplantation (FMT). FMT involves the introduction of a fecal suspension from a healthy donor into the gut of the infected patient to cure the CDI and replace depleted components of the gut microbiota. FMT is particularly effective and safe in curing CDI, using a colonoscope or enema to deliver 1 to 2 infusions. Given that 6425 CDIs were reported in Poland in 2014, practicing physicians should understand the benefits and limitations of FMT in CDI as this novel therapy has rapidly advanced to the level of the "standard-of-care" status in Australia, the United States, and many parts of Europe. FMT has been administered either as a suspension in saline, a highly refined liquid product which can be frozen, as lyophilized powder in capsules, and as an encapsulated spore preparation. The ultimate products to reach the market will be shaped by the indications approved by regulatory bodies. At present, the fecal suspension in saline remains the treatment of choice to terminate relapsing and severe CDI, which we will review here. The use of FMT for non-CDI indications, such as inflammatory bowel disease and irritable bowel syndrome, is likely to increase. At present, these indications remain in the domain of research institutions.}, }
@article {pmid26396721, year = {2015}, author = {Moossavi, S and Bishehsari, F and Ansari, R and Vahedi, H and Nasseri-Moghaddam, S and Merat, S and Sobhani, I and Keshavarzian, A and Malekzadeh, R}, title = {Minimum Requirements for Reporting Fecal Microbiota Transplant Trial.}, journal = {Middle East journal of digestive diseases}, volume = {7}, number = {}, pages = {177-180}, pmid = {26396721}, issn = {2008-5230}, }
@article {pmid26396717, year = {2015}, author = {Moossavi, S and Salimzadeh, H and Katoonizadeh, A and Mojarrad, A and Merat, D and Ansari, R and Vahedi, H and Merat, S and Malekzadeh, R}, title = {Physicians' Knowledge and Attitude Towards Fecal Microbiota Transplant in Iran.}, journal = {Middle East journal of digestive diseases}, volume = {7}, number = {}, pages = {155-160}, pmid = {26396717}, issn = {2008-5230}, abstract = {BACKGROUND Fecal microbiota transplant (FMT) is employed to replace the 'unhealthy' microbiota of the patient with the 'healthy' microbiota of a pre-screened healthy donor. Given the growing importance of gut microbiota dysbiosis in the pathogenesis of intestinal or extraintestinal diseases; it is conceivable that FMT becomes integrated in the routine clinical practice. Our objective was to assess the knowledge and attitude of the Iranian physicians towards FMT. METHODS We surveyed the participants of Iranian gastroenterology and hepatology 2014 conference. RESULTS Overall, 146 (68.5%) were familiar with FMT; of whom 132 (94.28%) were willing to accept FMT if scientifically and ethically approved and 115 (88.46%) were willing to refer their patients for FMT if indicated. In total, 42 (30.7%) had identified stool preparation as the most unappealing aspect of FMT, while 17 (11.6%) reported the therapeutic use of fecal material as the most unappealing and 39 (28.5%) indicated that both are equally unappealing. The doctors who had an overall positive opinion toward FMT reported less negative feelings towards FMT. CONCLUSION Iranian physicians are willing to accept FMT as a therapeutic option if it is scientifically justified and ethically approved. Nevertheless, physicians prefer to skip the stool preparation phase; as they are more in favour of synthetic microbiota as opposed to fecal microbiota.}, }
@article {pmid26395507, year = {2016}, author = {Cesaretti, M and Sulpice, L and Farges, O}, title = {Gastrointestinal bleeding from a submucosal duodenal tumor.}, journal = {Surgery}, volume = {159}, number = {2}, pages = {670-671}, doi = {10.1016/j.surg.2014.08.001}, pmid = {26395507}, issn = {1532-7361}, mesh = {Aged ; Duodenal Neoplasms/complications/*diagnosis ; Gastrointestinal Stromal Tumors/complications/*diagnosis ; Humans ; Intestinal Mucosa/*pathology ; Male ; Melena/*etiology ; }, }
@article {pmid26394496, year = {2015}, author = {Kuperman, AA and Koren, O}, title = {The Era of Fecal Microbiota Transplantation.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {17}, number = {8}, pages = {515-516}, pmid = {26394496}, issn = {1565-1088}, mesh = {*Enterocolitis, Pseudomembranous ; Feces/*microbiology ; *Gastrointestinal Tract ; Humans ; *Microbiota ; Transplants/*microbiology ; }, }
@article {pmid26394495, year = {2015}, author = {Cohen, NA and Ben Ami, R and Guzner-Gur, H and Santo, ME and Halpern, Z and Maharshak, N}, title = {Fecal Microbiota Transplantation for Clostridium difficile-Associated Diarrhea.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {17}, number = {8}, pages = {510-514}, pmid = {26394495}, issn = {1565-1088}, mesh = {Anti-Bacterial Agents/adverse effects ; Clostridioides difficile/isolation &amp; purification ; *Enterocolitis, Pseudomembranous/etiology/microbiology/therapy ; Feces/*microbiology ; *Gastrointestinal Tract/microbiology/physiopathology ; Humans ; *Microbiota/drug effects/physiology ; Outcome Assessment, Health Care ; Transplants/*microbiology ; }, abstract = {Clostridium difficile-associated diarrhea is a problem most hospital-based physicians will face in their career. This review aims to refresh current knowledge with regard to Clostridium difficile infection and bring physicians up to date with the latest developments in the growing field of fecal microbiota transplantation, the benefits it offers, and the promise this and other developments hold for the future.}, }
@article {pmid26386056, year = {2015}, author = {De Angelis, M and Montemurno, E and Vannini, L and Cosola, C and Cavallo, N and Gozzi, G and Maranzano, V and Di Cagno, R and Gobbetti, M and Gesualdo, L}, title = {Effect of Whole-Grain Barley on the Human Fecal Microbiota and Metabolome.}, journal = {Applied and environmental microbiology}, volume = {81}, number = {22}, pages = {7945-7956}, pmid = {26386056}, issn = {1098-5336}, mesh = {Adult ; Bacteria/classification/growth &amp; development/*isolation &amp; purification ; Diet ; Feces/microbiology ; Female ; Gas Chromatography-Mass Spectrometry ; Hordeum/chemistry/*metabolism ; Humans ; Italy ; Male ; *Metabolome ; *Microbiota ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Solid Phase Microextraction ; Triticum/chemistry/*metabolism ; }, abstract = {In this study, we compared the fecal microbiota and metabolomes of 26 healthy subjects before (HS) and after (HSB) 2 months of diet intervention based on the administration of durum wheat flour and whole-grain barley pasta containing the minimum recommended daily intake (3 g) of barley β-glucans. Metabolically active bacteria were analyzed through pyrosequencing of the 16S rRNA gene and community-level catabolic profiles. Pyrosequencing data showed that levels of Clostridiaceae (Clostridium orbiscindens and Clostridium sp.), Roseburia hominis, and Ruminococcus sp. increased, while levels of other Firmicutes and Fusobacteria decreased, from the HSB samples to the HS fecal samples. Community-level catabolic profiles were lower in HSB samples. Compared to the results for HS samples, cultivable lactobacilli increased in HSB fecal samples, while the numbers of Enterobacteriaceae, total coliforms, and Bacteroides, Porphyromonas, Prevotella, Pseudomonas, Alcaligenes, and Aeromonas bacteria decreased. Metabolome analyses were performed using an amino acid analyzer and gas chromatography-mass spectrometry solid-phase microextraction. A marked increase in short-chain fatty acids (SCFA), such as 2-methyl-propanoic, acetic, butyric, and propionic acids, was found in HSB samples with respect to the HS fecal samples. Durum wheat flour and whole-grain barley pasta containing 3% barley β-glucans appeared to be effective in modulating the composition and metabolic pathways of the intestinal microbiota, leading to an increased level of SCFA in the HSB samples.}, }
@article {pmid26383014, year = {2016}, author = {Gu, S and Chen, Y and Zhang, X and Lu, H and Lv, T and Shen, P and Lv, L and Zheng, B and Jiang, X and Li, L}, title = {Identification of key taxa that favor intestinal colonization of Clostridium difficile in an adult Chinese population.}, journal = {Microbes and infection}, volume = {18}, number = {1}, pages = {30-38}, doi = {10.1016/j.micinf.2015.09.008}, pmid = {26383014}, issn = {1769-714X}, mesh = {Asian People ; China ; Clostridioides difficile/*growth &amp; development ; Clostridium Infections/*microbiology ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; *Microbial Interactions ; Middle Aged ; Molecular Sequence Data ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Fecal microbial transplantation provides a high curative rate for recurrent Clostridium difficile infection (CDI). However, limitations associated with FMT drive the need to identify key taxa for selective probiotic therapy for prevention, treatment and cure of human CDI. CDI-associated changes in gut microbiota were investigated in adult patients in the Western countries and among infant population in China. However, there has been no such study involving adult patients in China. Therefore, using high throughput sequencing of the 16S ribosomal RNA V3 region and real-time quantitative polymerase chain reaction, we identified CDI-associated key taxa by comparing the fecal microbiota composition of 15 adult patients with CDI with those of 18 individuals with C. difficile-negative nosocomial diarrhea (CDN) and 25 healthy control subjects. Reduced fecal bacterial diversity and dramatic shifts of intestinal microbial composition in CDI and CDN groups were observed compared with healthy controls. Putative butyrate-producing anaerobic bacteria were significantly depleted whereas endotoxin-producing opportunistic pathogens and lactate-producing phylotypes increased dramatically in patients with CDI compared with healthy controls. Further screening of specific microbes causing diarrheal diseases and resistance against CDI is necessary.}, }
@article {pmid26374259, year = {2015}, author = {Fischer, M and Rex, DK and Sipe, BW}, title = {Letter: faecal microbiota transplantation in combination with fidaxomicin to treat severe complicated recurrent Clostridium difficile infection--authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {42}, number = {8}, pages = {1031}, doi = {10.1111/apt.13383}, pmid = {26374259}, issn = {1365-2036}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/*drug therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Vancomycin/*therapeutic use ; }, }
@article {pmid26374258, year = {2015}, author = {Pecere, S and Sabatelli, M and Fantoni, M and Ianiro, G and Gasbarrini, A and Cammarota, G}, title = {Letter: faecal microbiota transplantation in combination with fidaxomicin to treat severe complicated recurrent Clostridium difficile infection.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {42}, number = {8}, pages = {1030}, doi = {10.1111/apt.13362}, pmid = {26374258}, issn = {1365-2036}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/*drug therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Vancomycin/*therapeutic use ; }, }
@article {pmid26372091, year = {2016}, author = {Ojeda, P and Bobe, A and Dolan, K and Leone, V and Martinez, K}, title = {Nutritional modulation of gut microbiota - the impact on metabolic disease pathophysiology.}, journal = {The Journal of nutritional biochemistry}, volume = {28}, number = {}, pages = {191-200}, pmid = {26372091}, issn = {1873-4847}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; 3T32DK007074-39S1/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; DK097268/DK/NIDDK NIH HHS/United States ; R01 DK097268/DK/NIDDK NIH HHS/United States ; P30 DK42086/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Diet ; Diet, Western ; Humans ; Inflammation/complications ; Intestines/*microbiology ; Liver/physiopathology ; Obesity/complications/microbiology ; Prebiotics ; }, abstract = {The obesity epidemic afflicts over one third of the United States population. With few therapies available to combat obesity, a greater understanding of the systemic causes of this and other metabolic disorders is needed to develop new, effective treatments. The mammalian intestinal microbiota contributes to metabolic processes in the host. This review summarizes the research demonstrating the interplay of diet, intestinal microbiota and host metabolism. We detail the effects of diet-induced modifications in microbial activity and resultant impact on (1) sensory perception of macronutrients and total energy intake; (2) nutrient absorption, transport and storage; (3) liver and biliary function; (4) immune-mediated signaling related to adipose inflammation; and (5) circadian rhythm. We also discuss therapeutic strategies aimed to modify host-microbe interactions, including prebiotics, probiotics and postbiotics, as well as fecal microbiota transplantation. Elucidating the role of gut microbes in shaping metabolic homeostasis or dysregulation provides greater insight into disease development and a promising avenue for improved treatment of metabolic dysfunction.}, }
@article {pmid26370022, year = {2015}, author = {Cammarota, G and Ianiro, G and Magalini, S and Gasbarrini, A and Gui, D}, title = {Decrease in Surgery for Clostridium difficile Infection After Starting a Program to Transplant Fecal Microbiota.}, journal = {Annals of internal medicine}, volume = {163}, number = {6}, pages = {487-488}, doi = {10.7326/L15-5139}, pmid = {26370022}, issn = {1539-3704}, mesh = {*Clostridioides difficile ; Clostridium Infections/*epidemiology ; Female ; Humans ; Male ; }, }
@article {pmid26366577, year = {2015}, author = {Bejaoui, M and Sokol, H and Marteau, P}, title = {Targeting the Microbiome in Inflammatory Bowel Disease: Critical Evaluation of Current Concepts and Moving to New Horizons.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {33 Suppl 1}, number = {}, pages = {105-112}, doi = {10.1159/000437104}, pmid = {26366577}, issn = {1421-9875}, abstract = {Microorganisms present in the intestine possess proinflammatory or anti-inflammatory activities which may modulate inflammatory bowel disease (IBD). The concepts followed by researchers in trying to target the microbiota in IBD were to decrease pathogens or pathobionts, or only the microbial load, and more recently, to favor growth and persistence of favorable microorganisms. We review, here, those concepts and critically analyze the clinical data (especially randomized controlled trials) obtained using antibiotics and probiotics. We eventually present and criticize the rational and data obtained so far following new research strategies including the use of new probiotics, genetically modified organisms and fecal transplantation.}, }
@article {pmid26364372, year = {2015}, author = {von Ameln-Mayerhofer, A}, title = {[Clostridium difficile infection - an update].}, journal = {Medizinische Monatsschrift fur Pharmazeuten}, volume = {38}, number = {6}, pages = {211-8; quiz 219-20}, pmid = {26364372}, issn = {0342-9601}, mesh = {Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile ; Clostridium Infections/*drug therapy/epidemiology/microbiology ; Drug Resistance, Bacterial ; Humans ; Recurrence ; Treatment Failure ; }, abstract = {Clostridium difficile infection represents a severe illness which very often results in emergency surgery, intensive care unit stay or death. Although standard treatment procedures are well known and seem to be sufficient at the first glance, there is need for improvement of therapy guidelines due to high rates of recurrences or treatment failures. This article suggests some adjustments so far without claiming to be a complete review of all new development in this area. On the one hand, the recent actualization of the European guideline has been taken as a basis of this report; on the other hand some new highly promising developments in the treatment of CDI are exemplarily reported. Possibly the development with the highest impact in literature is fecal transplantation (or better said microbiome instillation). However, standard therapies need some critical review as well: an upgrading of vancomycin to first-line therapy and with a higher daily dose (250 mg qid) might be beneficial for many patients. For severe CDI, there is a recommendation against the usage of metronidazole, since vancomycin represents a better alternative. The dosage ofvancomycin might be further increased: although some authors are precautious in this point, dosage of vancomycin 500 mg qid should be favored. Last but not least, the pipeline bears some good tools for treatment of recurrent and complicated CDI, first data are promising and we hope for more.}, }
@article {pmid26364187, year = {2015}, author = {Del Coco, VF}, title = {[Microorganisms conferring beneficial health effects].}, journal = {Revista Argentina de microbiologia}, volume = {47}, number = {3}, pages = {171-173}, doi = {10.1016/j.ram.2015.08.001}, pmid = {26364187}, issn = {0325-7541}, mesh = {*Bacterial Physiological Phenomena ; Bacteriocins/pharmacology/therapeutic use ; Biological Therapy/methods ; Fecal Microbiota Transplantation ; Food Preservation/methods ; Fungi/*physiology ; Humans ; Intestines/microbiology ; Microbiota/*physiology ; *Probiotics/administration &amp; dosage/adverse effects ; *Symbiosis ; }, }
@article {pmid26363929, year = {2015}, author = {Cui, B and Li, P and Xu, L and Zhao, Y and Wang, H and Peng, Z and Xu, H and Xiang, J and He, Z and Zhang, T and Nie, Y and Wu, K and Fan, D and Ji, G and Zhang, F}, title = {Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis.}, journal = {Journal of translational medicine}, volume = {13}, number = {}, pages = {298}, pmid = {26363929}, issn = {1479-5876}, mesh = {Adolescent ; Adrenal Cortex Hormones/*therapeutic use ; Adult ; Child ; Colitis, Ulcerative/drug therapy/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Humans ; Male ; Microbiota ; Middle Aged ; Pilot Projects ; Prospective Studies ; Specimen Handling ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: The strategy of using fecal microbiota transplantation (FMT) for refractory ulcerative colitis (UC) remains unclear if single FMT failed to induce remission. This study aimed to evaluate the efficacy and safety of a designed step-up FMT strategy for the steroid-dependent UC.<br><br>METHODS: Fifteen patients with steroid-dependent UC were enrolled, and treated with step-up FMT strategy. Follow-up clinical data was collected for a minimum of 3&#xa0;months. Fecal microbiota composition before and post FMT of patients and related donors were analyzed by 16S rRNA sequencing.<br><br>RESULTS: Eight of fourteen (57.1&#xa0;%) patients achieved clinical improvement and were able to discontinue steroids following step-up FMT. One patient was lost to follow-up. Among the 8 patients who responded, five (35.7&#xa0;%) received one FMT therapy, one (7.1&#xa0;%) received two FMTs, and two (14.2&#xa0;%) received two FMTs plus a scheduled course of steroids. Four (28.6&#xa0;%) of the 8 patients who responded maintained long-term remission during follow-up (3-18&#xa0;months). Six patients (42.9&#xa0;%) failed to meet the criteria of clinical improvement and maintained steroid dependence, though three experienced transient or partial improvement. Microbiota analysis showed that FMT altered the composition greatly, and a microbiota composition highly similar to that of the donor emerged in the patients with successful treatment. No severe adverse events occurred during treatment and follow-up.<br><br>CONCLUSIONS: Step-up FMT strategy shows promise as a therapeutic strategy for patients with steroid-dependent UC, likely due to the successful restructuring of gut microbial composition.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT01790061.}, }
@article {pmid26362739, year = {2015}, author = {Costello, ME and Robinson, PC and Benham, H and Brown, MA}, title = {The intestinal microbiome in human disease and how it relates to arthritis and spondyloarthritis.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {29}, number = {2}, pages = {202-212}, doi = {10.1016/j.berh.2015.08.001}, pmid = {26362739}, issn = {1532-1770}, mesh = {Arthritis/*microbiology ; Dysbiosis/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Spondylarthritis/*microbiology ; }, abstract = {Humans and microbes have developed a symbiotic relationship over time, and alterations in this symbiotic relationship have been linked to several immune mediated diseases such as inflammatory bowel disease, type 1 diabetes and spondyloarthropathies. Improvements in sequencing technologies, coupled with a renaissance in 16S rRNA gene based community profiling, have enabled the characterization of microbiomes throughout the body including the gut. Improved characterization and understanding of the human gut microbiome means the gut flora is progressively being explored as a target for novel therapies including probiotics and faecal microbiota transplants. These innovative therapies are increasingly used for patients with debilitating conditions where conventional treatments have failed. This review discusses the current understanding of the interplay between host genetics and the gut microbiome in the pathogenesis of spondyloarthropathies, and how this may relate to potential therapies for these conditions.}, }
@article {pmid26362264, year = {2015}, author = {Fransen, F and Zagato, E and Mazzini, E and Fosso, B and Manzari, C and El Aidy, S and Chiavelli, A and D'Erchia, AM and Sethi, MK and Pabst, O and Marzano, M and Moretti, S and Romani, L and Penna, G and Pesole, G and Rescigno, M}, title = {BALB/c and C57BL/6 Mice Differ in Polyreactive IgA Abundance, which Impacts the Generation of Antigen-Specific IgA and Microbiota Diversity.}, journal = {Immunity}, volume = {43}, number = {3}, pages = {527-540}, doi = {10.1016/j.immuni.2015.08.011}, pmid = {26362264}, issn = {1097-4180}, mesh = {Animals ; Antigens, Bacterial/*immunology ; Bacteria/classification/genetics/immunology ; DNA, Bacterial/chemistry/genetics ; Feces/microbiology ; Flow Cytometry ; Genetic Variation/*immunology ; Host-Pathogen Interactions/immunology ; Immunization ; Immunoglobulin A/blood/*immunology/metabolism ; Metagenomics/methods ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microbiota/genetics/*immunology ; Peyer's Patches/immunology/metabolism/microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Salmonella typhimurium/genetics/immunology/physiology ; Species Specificity ; }, abstract = {The interrelationship between IgAs and microbiota diversity is still unclear. Here we show that BALB/c mice had higher abundance and diversity of IgAs than C57BL/6 mice and that this correlated with increased microbiota diversity. We show that polyreactive IgAs mediated the entrance of non-invasive bacteria to Peyer's patches, independently of CX3CR1(+) phagocytes. This allowed the induction of bacteria-specific IgA and the establishment of a positive feedback loop of IgA production. Cohousing of mice or fecal transplantation had little or no influence on IgA production and had only partial impact on microbiota composition. Germ-free BALB/c, but not C57BL/6, mice already had polyreactive IgAs that influenced microbiota diversity and selection after colonization. Together, these data suggest that genetic predisposition to produce polyreactive IgAs has a strong impact on the generation of antigen-specific IgAs and the selection and maintenance of microbiota diversity.}, }
@article {pmid26355220, year = {2015}, author = {Pérez-Gracia, MT and García, M and Suay, B and Mateos-Lindemann, ML}, title = {Current Knowledge on Hepatitis E.}, journal = {Journal of clinical and translational hepatology}, volume = {3}, number = {2}, pages = {117-126}, pmid = {26355220}, issn = {2225-0719}, abstract = {Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin(®).}, }
@article {pmid26354525, year = {2015}, author = {Yuille, S and Mackay, WG and Morrison, DJ and Tedford, MC}, title = {Optimising gut colonisation resistance against Clostridium difficile infection.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {34}, number = {11}, pages = {2161-2166}, pmid = {26354525}, issn = {1435-4373}, mesh = {Aged ; Aged, 80 and over ; Carrier State/epidemiology/immunology/*prevention &amp; control ; Clostridioides difficile/*immunology ; Cross Infection/epidemiology/immunology/*prevention &amp; control ; Enterocolitis, Pseudomembranous/epidemiology/microbiology/*prevention &amp; control ; Europe/epidemiology ; Fatty Acids/metabolism ; Gastrointestinal Tract/*immunology ; Humans ; Hydrogen-Ion Concentration ; Oxidation-Reduction ; United States/epidemiology ; }, abstract = {Clostridium difficile is the dominant cause of pseudomembranous colitis in nosocomial environments. C. difficile infection (CDI) generally affects elderly (≥65 years of age) hospital inpatients who have received broad-spectrum antimicrobial treatment. CDI has a 30 % risk of re-infection and a subsequent 60 % risk of relapse thereafter, leading to a high economic burden of over 7 billion pounds sterling and over 900,000 cases in the USA and Europe per annum. With the long-term consequences of faecal transplantation currently unknown, and limited spectrum of effective antibiotics, there is an urgent requirement for alternative means of preventing and treating CDI in high-risk individuals. Metagenomics has recently improved our understanding of the colonisation resistance barrier and how this could be optimised. pH, oxidation-reduction potentials and short-chain fatty acids have been suggested to inhibit C. difficile growth and toxin production in in vitro and in vivo studies. This review aims to pull together the evidence in support of a colonisation resistance barrier against CDI.}, }
@article {pmid26352106, year = {2016}, author = {Agrawal, M and Aroniadis, OC and Brandt, LJ and Kelly, C and Freeman, S and Surawicz, C and Broussard, E and Stollman, N and Giovanelli, A and Smith, B and Yen, E and Trivedi, A and Hubble, L and Kao, D and Borody, T and Finlayson, S and Ray, A and Smith, R}, title = {The Long-term Efficacy and Safety of Fecal Microbiota Transplant for Recurrent, Severe, and Complicated Clostridium difficile Infection in 146 Elderly Individuals.}, journal = {Journal of clinical gastroenterology}, volume = {50}, number = {5}, pages = {403-407}, doi = {10.1097/MCG.0000000000000410}, pmid = {26352106}, issn = {1539-2031}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Humans ; Male ; Recurrence ; Retrospective Studies ; Severity of Illness Index ; Surveys and Questionnaires ; Time Factors ; Treatment Outcome ; }, abstract = {OBJECTIVES: Clostridium difficile infection (CDI) in the elderly has a higher prevalence, greater morbidity and mortality, and lower response to conventional treatment than the general population. Fecal microbiota transplant (FMT) is highly effective therapy for CDI but has not been studied specifically in the elderly. This study aims to determine the long-term efficacy and safety of FMT for recurrent (RCDI), severe (SCDI), and complicated (CCDI) CDI in elderly patients.<br><br>METHODS: A multicenter, long-term follow-up study was performed with demographic, pre-FMT, and post-FMT data collected from elderly patients with RCDI, SCDI, and CCDI, through a 47-item questionnaire. Outcome measures included primary and secondary cure rates, early (<12 wk) and late (&#x2265;12 wk) recurrence rates, and adverse events (AEs), including post-FMT diagnoses.<br><br>RESULTS: Of 168 eligible patients, 146 patients met the inclusion criteria. Of these, 68.5% were women. The mean (range) age was 78.6 (65 to 97) years and the follow-up period was 12.3 (1 to 48) months. FMT was performed for RCDI in 89 (61%), SCDI in 45 (30.8%), and CCDI in 12 (8.2%) patients. The primary and secondary cure rates were 82.9% and 95.9%, respectively. Early and late recurrences occurred in 25 and 6 patients, respectively. AEs included CDI-negative diarrhea in 7 (4.8%) and constipation in 4 (2.7%) patients. Serious AEs, recorded in 6 patients, were hospital admissions for CDI-related diarrhea, one of which culminated in death. New diagnoses post-FMT included microscopic colitis (2), Sjogren syndrome (1), follicular lymphoma (1), contact dermatitis and idiopathic Bence-Jones proteinuria (1), and laryngeal carcinoma (1)-all, however, were associated with predisposing factors.<br><br>CONCLUSIONS: FMT is a safe and effective treatment option for RCDI, SCDI, and CCDI in elderly patients.}, }
@article {pmid26349235, year = {2015}, author = {Rodionova, EI and Kochevalinaa, MY and Kotenkova, EV and Morozova, V and Kogun, GA and Bataeva, EL and Ambaryan, AV}, title = {[Detection of Volatile Organic Compounds Associated with Hepatocellular Carcinoma by Macrosmatic Animals: Approaches to the Search for New Tumor Markers].}, journal = {Izvestiia Akademii nauk. Seriia biologicheskaia}, volume = {}, number = {3}, pages = {293-301}, pmid = {26349235}, issn = {1026-3470}, mesh = {Animals ; Biomarkers, Tumor/*urine ; Carcinoma, Hepatocellular/*urine ; Dogs ; Liver Neoplasms/*urine ; Mice ; Odorants ; *Smell ; Volatile Organic Compounds/urine ; }, abstract = {Macrosmatic animals (dogs and mice) have been proved to be able to distinguish between the urine or feces of mice with transplanted hepatocellular carcinoma and those of healthy mice by odor. The chemical composition of animal excreta was found to change with tumor growth; however, it is not clear yet if this results from tumor growth itself, inflammation, or immune response. We suggested that the use of the ability of macrosmatic animals to compare odor mixtures combined with mouse cancer models is a promising trend in the search for new tumor markers.}, }
@article {pmid26348073, year = {2015}, author = {Konturek, PC and Haziri, D and Brzozowski, T and Hess, T and Heyman, S and Kwiecien, S and Konturek, SJ and Koziel, J}, title = {Emerging role of fecal microbiota therapy in the treatment of gastrointestinal and extra-gastrointestinal diseases.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {66}, number = {4}, pages = {483-491}, pmid = {26348073}, issn = {1899-1505}, mesh = {Animals ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {In the recent decade our understanding of the role of the human gut microbiome has been revolutionized by advances in development of molecular methods. Approximately, up to 100 trillion (10(14)) microorganisms per human body colonize the intestinal tract making an additional acquired organ that provides many vital functions to the host. A healthy gut microbiome can be defined by the presence of the various classes of microbes that enhance metabolism, resistance to infection and inflammation, prevention against cancer and autoimmunity and that positively influence so called braingut axis. Diet represents one of the most important driving forces that besides environmental and genetic factors, can define and influence the microbial composition of the gut. Aging process due to different changes in gut physiology (i.e. gastric hypochlorhydria, motility disorders, use of drugs, degenerative changes in enteric nervous system) has a profound effect on the composition, diversity and functional features of gut microbiota. A perturbed aged gut microbiome has been associated with the increasing number of gastrointestinal (e.g. Clostridium difficile infection - CDI) and non-gastrointestinal diseases (metabolic syndrome, diabetes mellitus, fatty liver disease, atherosclerosis etc.). Fecal microbiota transplantation (FMT) is a highly effective method in the treatment of refractory CDI. FMT is the term used when stool is taken from a healthy individual and instilled during endoscopy (colonoscopy or enteroscopy) into a gut of the sick person to cure certain disease. FMT represents an effective therapy in patient with recurrent CDI and the effectiveness of FMT in the prevention of CDI recurrence had reached approx. 90%. There is also an increasing evidence that the manipulation of gut microbiota by FMT represents a promising therapeutic method in patients with inflammatory bowel disease and irritable bowel syndrome. There is also an increased interest in the role of FMT for the treatment of metabolic syndrome and obesity which collectively present the greatest health challenge in the developed world nowadays. Targeting of gut microbiota by FMT represents an exciting new frontier in the prevention and management of gastrointestinal and non-gastrointestinal diseases that awaits further studies in preclinical and clinical settings.}, }
@article {pmid26346682, year = {2015}, author = {Salzberger, B and Rauscher, C}, title = {[The microbiome of the gut in critically ill patients].}, journal = {Medizinische Klinik, Intensivmedizin und Notfallmedizin}, volume = {110}, number = {7}, pages = {521-525}, pmid = {26346682}, issn = {2193-6226}, mesh = {Critical Care/methods ; *Critical Illness/therapy ; Enterocolitis, Pseudomembranous/microbiology/therapy ; Fecal Microbiota Transplantation ; Host-Pathogen Interactions/physiology ; Humans ; Intestines/*microbiology ; *Microbiota/physiology ; Probiotics/therapeutic use ; Symbiosis/physiology ; }, abstract = {BACKGROUND: The complexity and diversity of the human intestinal microbiome has only recently been characterized. The multiple metabolic and immunologic effects of the bacterial flora have demonstrated the symbiosis between the microbiome and its host. This symbiosis is disturbed in a multitude of diseases, especially in critically ill patients.<br><br>OBJECTIVES: A review of the changes in the intestinal microbiome of critically ill patients and the use of probiotics.<br><br>MATERIAL AND METHODS: Nonsystematic literature search in PubMed on the topics: (1) changes in the intestinal microbiome in critically ill patients, (2) interventions using probiotics in critically ill patients, and (3) use of fecal transplantation in Clostridium difficile colitis.<br><br>RESULTS: Trauma, sepsis, systemic inflammatory response syndrome, and other conditions lead to shifts in the composition of the intestinal microbiome, which are correlated with clinical outcome. The most obvious change is a profound loss of obligate anaerobe bacteria, leading also to metabolic changes. Probiotics have been used in several studies and show efficacy in the reduction of infectious complication but not in overall mortality. C. difficile colitis as the model disease for a disturbed microbiome can be treated effectively by transfer of donor feces, which also restores the diversity of the microbiome.<br><br>CONCLUSION: Taking into account the successful intervention of fecal transplantation on the intestinal microbiome, new products developed using the current knowledge of the intestinal microbiome could be more effective.}, }
@article {pmid26344412, year = {2016}, author = {Rao, K and Safdar, N}, title = {Fecal microbiota transplantation for the treatment of Clostridium difficile infection.}, journal = {Journal of hospital medicine}, volume = {11}, number = {1}, pages = {56-61}, pmid = {26344412}, issn = {1553-5606}, support = {UL1 TR000433/TR/NCATS NIH HHS/United States ; R21 AI120599/AI/NIAID NIH HHS/United States ; R03 AG040669/AG/NIA NIH HHS/United States ; P30 AG024824/AG/NIA NIH HHS/United States ; I01 CX000391/CX/CSRD VA/United States ; 2UL1TR000433/TR/NCATS NIH HHS/United States ; AG-024824/AG/NIA NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/diagnosis/*therapy ; Diarrhea/microbiology ; Enterocolitis, Pseudomembranous/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Gastrointestinal Microbiome ; Humans ; Recurrence ; }, abstract = {Clostridium difficile, a major cause of healthcare-associated diarrhea due to perturbation of the normal gastrointestinal microbiome, is responsible for significant morbidity, mortality, and healthcare expenditures. The incidence and severity of C difficile infection (CDI) is increasing, and recurrent disease is common. Recurrent infection can be difficult to manage with conventional antibiotic therapy. Fecal microbiota transplantation (FMT), which involves instillation of stool from a healthy donor into the gastrointestinal tract of the patient, restores the gut microbiome to a healthy state. FMT has emerged as a promising new treatment for CDI. There are limited data on FMT for treatment of primary CDI, but FMT appears safe and effective for recurrent CDI. The safety and efficacy of FMT in patients with severe primary or severe recurrent CDI has not been established. Patients with inflammatory bowel disease (IBD) who undergo FMT for CDI may be at increased risk of IBD flare, and caution should be exercised with use of FMT in that population. The long-term safety of FMT is unknown; thus, rigorously conducted prospective studies are needed.}, }
@article {pmid26343156, year = {2016}, author = {Múñez, E and Ramos, A and Baños, I and Cuervas-Mons, V}, title = {[Fecal transplantation for the treatment of relapsing diarrhea associated with Clostridium difficile infection in a liver transplantation patient].}, journal = {Medicina clinica}, volume = {146}, number = {1}, pages = {e3-4}, doi = {10.1016/j.medcli.2015.06.017}, pmid = {26343156}, issn = {1578-8989}, mesh = {*Clostridioides difficile ; Clostridium Infections/etiology/*therapy ; Diarrhea/etiology/*therapy ; Fatal Outcome ; *Fecal Microbiota Transplantation ; Humans ; *Liver Transplantation ; Male ; Middle Aged ; Postoperative Complications/*therapy ; Recurrence ; }, }
@article {pmid26338727, year = {2016}, author = {Marchesi, JR and Adams, DH and Fava, F and Hermes, GD and Hirschfield, GM and Hold, G and Quraishi, MN and Kinross, J and Smidt, H and Tuohy, KM and Thomas, LV and Zoetendal, EG and Hart, A}, title = {The gut microbiota and host health: a new clinical frontier.}, journal = {Gut}, volume = {65}, number = {2}, pages = {330-339}, pmid = {26338727}, issn = {1468-3288}, mesh = {Animals ; Autoimmune Diseases/microbiology ; Bacteria/metabolism ; Colitis, Ulcerative/microbiology ; Crohn Disease/microbiology ; Gastrointestinal Microbiome/*physiology ; *Health Status ; Humans ; Inflammatory Bowel Diseases/microbiology ; Liver Diseases/microbiology ; Liver Diseases, Alcoholic/microbiology ; Non-alcoholic Fatty Liver Disease/microbiology ; Obesity/etiology ; Polyphenols/metabolism ; Pouchitis/microbiology ; Prebiotics ; Probiotics ; }, abstract = {Over the last 10-15 years, our understanding of the composition and functions of the human gut microbiota has increased exponentially. To a large extent, this has been due to new 'omic' technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.}, }
@article {pmid26338196, year = {2015}, author = {Boursi, B and Mamtani, R and Haynes, K and Yang, YX}, title = {Recurrent antibiotic exposure may promote cancer formation--Another step in understanding the role of the human microbiota?.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {51}, number = {17}, pages = {2655-2664}, pmid = {26338196}, issn = {1879-0852}, support = {K23 CA187185/CA/NCI NIH HHS/United States ; UL1 TR000003/TR/NCATS NIH HHS/United States ; UL1TR000003/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Bacteria/classification/*drug effects ; Breast Neoplasms/epidemiology ; Case-Control Studies ; Databases, Factual/statistics &amp; numerical data ; Electronic Health Records/statistics &amp; numerical data ; Esophageal Neoplasms/epidemiology ; Female ; Humans ; Incidence ; Lung Neoplasms/epidemiology ; Male ; Microbiota/*drug effects ; Middle Aged ; Neoplasms/*epidemiology ; Pancreatic Neoplasms/epidemiology ; Prostatic Neoplasms/epidemiology ; Risk Factors ; Stomach Neoplasms/epidemiology ; Time Factors ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Bacterial dysbiosis was previously described in human malignancies. In a recent animal model, tumour susceptibility was transmitted using faecal transplantation. Our aim was to evaluate possible association between antibiotic exposure and cancer risk.<br><br>METHODS: We conducted nested case-control studies for 15 common malignancies using a large population-based electronic medical record database. Cases were defined as those with any medical code for the specific malignancy. Individuals with familial cancer syndromes were excluded. For every case, four eligible controls matched on age, sex, practice site and duration of follow-up before index-date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy >1 year before index-date. Adjusted odds-ratios (AORs) and 95% confidence intervals (CIs) were estimated for each antibiotic type using conditional logistic regression.<br><br>RESULTS: 125,441 cases and 490,510 matched controls were analysed. For gastro-intestinal malignancies, the use of penicillin was associated with an elevated risk of oesophageal, gastric and pancreatic cancers. The association increased with the number of antibiotic courses and reached 1.4 for gastric cancers associated with >5 courses of penicillin (95% CI 1.2-1.8). Lung cancer risk increased with the use of penicillin, cephalosporins, or macrolides (AOR for >5 courses of penicillin: 1.4 95% CI 1.3-1.6). The risk of prostate cancer increased modestly with the use of penicillin, quinolones, sulphonamides and tetracyclines. The risk of breast cancer was modestly associated with exposure to sulphonamides. There was no association between the use of anti-virals and anti-fungals and cancer risk.<br><br>CONCLUSION: Recurrent exposure to certain antibiotics may be associated with cancer risk in specific organ sites.}, }
@article {pmid26334306, year = {2015}, author = {Caballero, S and Carter, R and Ke, X and Sušac, B and Leiner, IM and Kim, GJ and Miller, L and Ling, L and Manova, K and Pamer, EG}, title = {Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae.}, journal = {PLoS pathogens}, volume = {11}, number = {9}, pages = {e1005132}, pmid = {26334306}, issn = {1553-7374}, support = {R01 AI42135/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; AI95706/AI/NIAID NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; }, mesh = {Ampicillin/adverse effects ; Animals ; Anti-Bacterial Agents/adverse effects/pharmacology ; Carbapenems/pharmacology ; Colony Count, Microbial ; Drug Resistance, Bacterial ; Enteritis/*microbiology/pathology/prevention &amp; control ; Enterococcus faecium/drug effects/growth &amp; development/isolation &amp; purification/*physiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/drug effects ; Gram-Positive Bacterial Infections/*microbiology/pathology/prevention &amp; control ; Host-Pathogen Interactions ; In Situ Hybridization, Fluorescence ; Intestinal Mucosa/drug effects/*microbiology/pathology ; Klebsiella Infections/*microbiology/pathology/prevention &amp; control ; Klebsiella pneumoniae/drug effects/growth &amp; development/isolation &amp; purification/*physiology ; Mice, Inbred C57BL ; Microbial Interactions ; Specific Pathogen-Free Organisms ; Vancomycin-Resistant Enterococci/drug effects/growth &amp; development/isolation &amp; purification/*physiology ; }, abstract = {Antibiotic resistance among enterococci and γ-proteobacteria is an increasing problem in healthcare settings. Dense colonization of the gut by antibiotic-resistant bacteria facilitates their spread between patients and also leads to bloodstream and other systemic infections. Antibiotic-mediated destruction of the intestinal microbiota and consequent loss of colonization resistance are critical factors leading to persistence and spread of antibiotic-resistant bacteria. The mechanisms underlying microbiota-mediated colonization resistance remain incompletely defined and are likely distinct for different antibiotic-resistant bacterial species. It is unclear whether enterococci or γ-proteobacteria, upon expanding to high density in the gut, confer colonization resistance against competing bacterial species. Herein, we demonstrate that dense intestinal colonization with vancomycin-resistant Enterococcus faecium (VRE) does not reduce in vivo growth of carbapenem-resistant Klebsiella pneumoniae. Reciprocally, K. pneumoniae does not impair intestinal colonization by VRE. In contrast, transplantation of a diverse fecal microbiota eliminates both VRE and K. pneumoniae from the gut. Fluorescence in situ hybridization demonstrates that VRE and K. pneumoniae localize to the same regions in the colon but differ with respect to stimulation and invasion of the colonic mucus layer. While VRE and K. pneumoniae occupy the same three-dimensional space within the gut lumen, their independent growth and persistence in the gut suggests that they reside in distinct niches that satisfy their specific in vivo metabolic needs.}, }
@article {pmid26329908, year = {2015}, author = {Chemaly, RF and Ghantoji, SS and Huber, T and Raad, II and Jinadatha, C and Stibich, M}, title = {Innovative Analysis of the Sequenced Patterns of Vancomycin-Resistant Enterococci Strains to Determine Clonal Transmission in a Hospital Setting.}, journal = {Infection control and hospital epidemiology}, volume = {36}, number = {12}, pages = {1461-1463}, doi = {10.1017/ice.2015.208}, pmid = {26329908}, issn = {1559-6834}, mesh = {Cancer Care Facilities ; Cross Infection/epidemiology/*microbiology ; Enterococcus/isolation &amp; purification ; Feces/microbiology ; Gram-Positive Bacterial Infections/epidemiology/*microbiology/transmission ; Hospitals ; Humans ; Leukemia ; Polymerase Chain Reaction ; Stem Cell Transplantation ; Texas/epidemiology ; Vancomycin-Resistant Enterococci/*genetics ; }, abstract = {Isolates from patients who acquired vancomycin-resistant enterococci (VRE) were examined for the frequency of genetically indistinguishable strains on leukemia and stem cell transplant units at a major cancer center for 1 year. A total of 14 strains recurred, primarily on the same floor and in the same service unit an average of 49 days apart.}, }
@article {pmid26319378, year = {2015}, author = {Rebizak, E and Sierant, K and Łabuzek, K and Okopień, B}, title = {[Fecal transplantation the future therapy?].}, journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego}, volume = {39}, number = {230}, pages = {73-76}, pmid = {26319378}, issn = {1426-9686}, mesh = {Biological Therapy/*methods ; Clostridioides difficile ; Clostridium Infections/therapy ; Diabetes Complications ; Donor Selection/methods ; Drug Resistance, Microbial ; Enterocolitis, Pseudomembranous/*microbiology/therapy ; Feces/*microbiology ; Forecasting ; Gastroenteritis/*microbiology/*therapy ; Humans ; Inflammatory Bowel Diseases/microbiology/therapy ; Irritable Bowel Syndrome/*microbiology/*therapy ; Microbiota ; Obesity/complications ; Probiotics/therapeutic use ; Recurrence ; Transplantation/methods ; }, abstract = {Intestinal bacteria play an important role in human physiology, taking part in the metabolism, absorption of nutrients and regulation of the immune system. In many illnesses the bacterial imbalance in the digestive tract occurs, and fecal transplantation is one method that allows you to restore the balance. The essence of the described method is to replace the pathogenesis, abnormal bacterial flora with the flora occurring in normal healthy individuals. So far, the main use of the method described in the article is resistant to antibiotics Clostridium difficile infection, which gives you a chance to avoid total colectomy. The article presents an accurate description of the same procedure to prepare the material, the selection of donor, recipient preparation and diseases, such as inflammatory bowel diseases, irritable bowel syndrome, diabetes and obesity, in which this method of treatment is currently practised.}, }
@article {pmid26310797, year = {2016}, author = {Benlice, C and Yildiz, M and Baghaki, S and Erguner, I and Olgun, DC and Batur, S and Erdamar, S and Ambarcioglu, P and Hamzaoglu, I and Karahasanoglu, T and Baca, B}, title = {Fistula tract curettage and the use of biological dermal plugs improve high transsphincteric fistula healing in an animal model.}, journal = {International journal of colorectal disease}, volume = {31}, number = {2}, pages = {291-299}, pmid = {26310797}, issn = {1432-1262}, mesh = {*Acellular Dermis ; Animals ; Curettage/*methods ; *Disease Models, Animal ; Female ; Fissure in Ano/pathology/physiopathology/*surgery ; Humans ; Magnetic Resonance Imaging ; Rabbits ; *Skin Transplantation ; Transplantation, Autologous ; *Wound Healing ; }, abstract = {PURPOSE: The treatment of high transsphincteric fistula is a complex procedure, which may be associated with the risk of recurrence and fecal incontinence. In this study, we used an animal model to compare different types of sphincter-preserving treatments for transsphincteric fistula.<br><br>METHODS: Sixteen female New Zealand rabbits, weighing 2.8-4.8 kg underwent a surgical creation of high transsphincteric fistula. After 6 weeks, magnetic resonance imaging (MRI) was performed in order to confirm fistula formation and measure the fistula diameter. The rabbits were divided into three groups. Group 1 received no plug treatment (control). Autologous dermal graft and acellular dermal matrix were used as a plug in groups 2 and 3, respectively. Five weeks after treatment, fistula tract healing was determined by measuring the largest fistula diameter with MRI. All rabbits were euthanized and the anorectum excised en bloc for histopathological examination.<br><br>RESULTS: According to the MRI findings, all groups showed significant healing after the treatment (p&#x2009;<&#x2009;0.05). The healing rate of fistula diameters after treatment was 40, 66, and 29% in the control, dermal graft, and acellular dermal matrix groups, respectively. In terms of negative healing parameters such as neutrophil, eosinophil, lymphocyte, and plasmocyte accumulation, dermal graft and acellular dermal matrix groups showed significantly lower results than those in the control group (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: According to MRI and histopathological results, fistula tract curettage and fistula orifice closure improved transsphincteric anal fistula healing. Additionally, in this study, plug treatment favoring autologous dermal graft resulted in better healing.}, }
@article {pmid26308202, year = {2015}, author = {Cardamone, S and Creighton, S}, title = {A gynaecologic perspective on cloacal malformations.}, journal = {Current opinion in obstetrics &amp; gynecology}, volume = {27}, number = {5}, pages = {345-352}, doi = {10.1097/GCO.0000000000000205}, pmid = {26308202}, issn = {1473-656X}, mesh = {Adolescent ; Adult ; Anal Canal/*abnormalities/physiopathology/surgery ; Child ; Colpotomy ; Family Planning Services ; Fecal Incontinence/etiology ; Female ; Fertility Preservation/*methods ; Humans ; Hydrocolpos/*diagnosis/physiopathology/psychology/surgery ; Kidney/*abnormalities/physiopathology/surgery ; Pregnancy ; Quality of Life ; Plastic Surgery Procedures/*methods ; Rectum/*abnormalities/physiopathology/surgery ; Sexual Dysfunction, Physiological/etiology/psychology/*surgery ; Urinary Incontinence/etiology ; }, abstract = {PURPOSE OF REVIEW: Advances in surgical reconstruction of cloacal malformations have led to better functional outcomes and quality of life. As a result, adolescents and women born with these complex malformations will have the same aspirations as their peers including sexual relationships and fertility.<br><br>RECENT FINDINGS: Currently, there is a paucity of data on gynaecologic outcomes and sexual function, and obstetric data are limited primarily to case reports. Making evidence-based clinical recommendations is difficult for gynaecologic providers. Unique gynaecologic issues can arise in infancy, adolescence or adulthood. Recognition and appropriate management of these complications is imperative to maximize sexual esteem and preserve future fertility. Pregnancy requires adequate prenatal preparation and specialized multidisciplinary care under an experienced obstetrician and urologist.<br><br>SUMMARY: This review highlights the issues that may be encountered in providing gynaecologic care to patients with cloacal malformations, presents the available literature to provide informative evidence and identifies gaps in knowledge in order to suggest potential future research opportunities.}, }
@article {pmid26305138, year = {2015}, author = {Baumgart, DC}, title = {[The human microbiome].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {140}, number = {19}, pages = {1451-1456}, doi = {10.1055/s-0041-103202}, pmid = {26305138}, issn = {1439-4413}, mesh = {Clostridioides difficile ; Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, abstract = {Research into the human microbiome will substantially enhance our understanding of inflammatory, metabolic and malignant diseases. The complexity of this research area can only be addressed by an interdisciplinary translational approach including bioinformatics. Data derived from pure in silico analyses and statistical associations will not automatically translate into sound clinical concepts, as we have learned previously in genetics. Potential targets for future treatment strategies include the proven impact of nutrition and medication on microbial diversity and therapeutic effects of microbial metabolic processes and metabolites. Fecal microbial transplantation (FMT) beyond its indication in refractory Clostridium difficile infection (CDI) should be held against the same standards and regulated by the same procedures that are applied to all investigational compounds and treatments prior to their approval. Donor fidelity, sample processing and recipient safety (including the role of fecal pathogens and toxins) need thorough scientific investigation and evaluation in clinical trials with objective outcome parameters prior to any recommendations for clinical practice.}, }
@article {pmid26302500, year = {2015}, author = {Malnick, SD and Oppenheim, A and Melzer, E}, title = {Immune Thrombocytopenia Caused by Fecal Microbial Transplantation in a Patient With Severe Recurrent Clostridium difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {49}, number = {10}, pages = {888-889}, doi = {10.1097/MCG.0000000000000404}, pmid = {26302500}, issn = {1539-2031}, mesh = {Aged, 80 and over ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*adverse effects ; Female ; Humans ; Purpura, Thrombocytopenic, Idiopathic/*etiology ; Recurrence ; }, }
@article {pmid26301122, year = {2015}, author = {Malnick, S and Melzer, E}, title = {Human microbiome: From the bathroom to the bedside.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {6}, number = {3}, pages = {79-85}, pmid = {26301122}, issn = {2150-5330}, abstract = {The human gut contains trillions of bacteria, the major phylae of which include Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria. Fecal microbial transplantation (FMT) has been known of for many years but only recently has been subjected to rigorous examination. We review the evidence regarding FMT for recurrent Clostridium difficile infection which has resulted in it being an approved treatment. In addition there is some evidence for its use in both irritable bowel syndrome and inflammatory bowel disease. Further research is needed in order to define the indications for FMT and the most appropriate method of administration.}, }
@article {pmid26299453, year = {2015}, author = {Ussar, S and Griffin, NW and Bezy, O and Fujisaka, S and Vienberg, S and Softic, S and Deng, L and Bry, L and Gordon, JI and Kahn, CR}, title = {Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome.}, journal = {Cell metabolism}, volume = {22}, number = {3}, pages = {516-530}, pmid = {26299453}, issn = {1932-7420}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK030292/DK/NIDDK NIH HHS/United States ; P30 DK036836/DK/NIDDK NIH HHS/United States ; DK31036/DK/NIDDK NIH HHS/United States ; T32 DK007120/DK/NIDDK NIH HHS/United States ; P30DK036836/DK/NIDDK NIH HHS/United States ; R01 DK031036/DK/NIDDK NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; R01 DK082659/DK/NIDDK NIH HHS/United States ; DK78669/DK/NIDDK NIH HHS/United States ; DK007120/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; P30DK034854/DK/NIDDK NIH HHS/United States ; K12 HD000850/HD/NICHD NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; DK30292/DK/NIDDK NIH HHS/United States ; R01 DK033201/DK/NIDDK NIH HHS/United States ; DK70977/DK/NIDDK NIH HHS/United States ; DK33201/DK/NIDDK NIH HHS/United States ; DK82659/DK/NIDDK NIH HHS/United States ; R37 DK031036/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Diabetes Mellitus/*genetics/*microbiology/pathology ; Diet ; *Gastrointestinal Microbiome ; Gene-Environment Interaction ; Genotype ; Insulin Resistance ; Male ; Metabolic Syndrome/*genetics/*microbiology/pathology ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Obesity/*genetics/*microbiology/pathology ; Phenotype ; Weight Gain ; }, abstract = {Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice-obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac from Taconic-plus three derivative lines generated by breeding these strains in a new, common environment. Analysis of metabolic parameters and gut microbiota in all strains and their environmentally normalized derivatives revealed strong interactions between microbiota, diet, breeding site, and metabolic phenotype. Strain-dependent and strain-independent correlations were found between specific microbiota and phenotypes, some of which could be transferred to germ-free recipient animals by fecal transplantation. Environmental reprogramming of microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus, development of obesity/metabolic syndrome is the result of interactions between gut microbiota, host genetics, and diet. In permissive genetic backgrounds, environmental reprograming of microbiota can ameliorate development of metabolic syndrome.}, }
@article {pmid26288277, year = {2015}, author = {Damman, CJ and Brittnacher, MJ and Westerhoff, M and Hayden, HS and Radey, M and Hager, KR and Marquis, SR and Miller, SI and Zisman, TL}, title = {Low Level Engraftment and Improvement following a Single Colonoscopic Administration of Fecal Microbiota to Patients with Ulcerative Colitis.}, journal = {PloS one}, volume = {10}, number = {8}, pages = {e0133925}, pmid = {26288277}, issn = {1932-6203}, support = {P30 DK089507/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Colitis, Ulcerative/*microbiology/pathology/*therapy ; Colon/*microbiology/*pathology ; Colonoscopy/methods ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; Middle Aged ; Prospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) is an investigational treatment for diseases thought to involve alterations in the intestinal microbiota including ulcerative colitis (UC). Case reports have described therapeutic benefit of FMT in patients with UC, possibly due to changes in the microbiota. We measured the degree to which the transplanted microbiota engraft following FMT in patients with UC using a donor similarity index (DSI).<br><br>METHODS: Seven patients with mild to moderate UC (UC disease activity index scores 3-10) received a single colonoscopic administration of FMT. Metagenomic sequence data from stool were analyzed using an alignment-free comparison tool, to measure the DSI, and a phylogenetic analysis tool, to characterize taxonomic changes. Clinical, endoscopic, histologic, and fecal calprotectin outcome measures were also collected.<br><br>RESULTS: One of 5 patients from whom sequencing data were available achieved the primary endpoint of 50% donor similarity at week 4; an additional 2 patients achieved 40% donor similarity. One patient with 40% donor similarity achieved clinical and histologic remission 1 month after FMT. However, these were lost by 2-3 months, and loss correlated with a decrease in DSI. The remaining patients did not demonstrate clinical response or remission. Histology scores improved in all but 1 patient. No patients remained in remission at 3 months after FMT.<br><br>CONCLUSIONS: Following a single colonoscopic fecal transplant, a DSI of 40-50% is achieved in about two-thirds of recipients. This level of engraftment correlated with a temporary clinical improvement in only 1/5 patients. Larger sample sizes could further validate this method for measuring engraftment, and changes in transplant frequency or method might improve microbiota engraftment and efficacy.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT01742754.}, }
@article {pmid26288096, year = {2014}, author = {Keller, PM and Weber, MH}, title = {Rational Therapy of Clostridium difficile Infections.}, journal = {Viszeralmedizin}, volume = {30}, number = {5}, pages = {304-309}, pmid = {26288096}, issn = {1662-6664}, abstract = {BACKGROUND: Clostridium difficile infections (CDI) are increasingly important in patients with antibiotic treatments, ranging from mild, self-limiting to severe, life-threatening disease. Currently, diagnostic algorithms and treatment guidelines are being adapted to novel tests and therapeutic options for recurrent CDI.<br><br>METHODS: A systematic literature search using the terms 'Clostridium difficile' and 'treatment' was carried out. Current guidelines are being discussed from a clinical point of view.<br><br>RESULTS: State-of-the-art diagnostics for C. difficile diagnosis rely on the patient's history, clinical symptoms, and laboratory examination of stool. Recommendations are in favour of glutamate dehydrogenase (GDH) screening tests and confirmatory detection of C. difficile toxin genes (polymerase chain reaction (PCR)). Therapeutic strategies depend on disease severity (mild vs. severe) and endorse metronidazole and vancomycin as well as fidaxomycin for recurrent disease. In very severe cases, surgical therapy is recommended. For relapsing diseases, faecal transfer is considered as a therapeutic option if available.<br><br>CONCLUSION: Current guidelines have been adapted to new pathways in diagnosing CDI and have included statements on novel therapeutic options such as fidaxomycin and faecal transplant for recurrent disease. Depending on the severity of the disease, standard therapy with either metronidazole or vancomycin is recommended.}, }
@article {pmid26277232, year = {2015}, author = {Rogler, G}, title = {Where are we heading to in pharmacological IBD therapy?.}, journal = {Pharmacological research}, volume = {100}, number = {}, pages = {220-227}, doi = {10.1016/j.phrs.2015.07.005}, pmid = {26277232}, issn = {1096-1186}, mesh = {Animals ; Cell Adhesion Molecules/metabolism ; Humans ; Inflammatory Bowel Diseases/*drug therapy/metabolism ; Interleukin-10/metabolism ; }, abstract = {After a relatively long time of failed developments and negative clinical trials in pharmacological inflammatory bowel disease (IBD) therapy we now phase a time of a great number of successful studies and new therapy principles that will most likely make it into clinical practice. This will change the landscape of IBD therapy in future markedly. Many new therapeutic principles have been developed and old ones that seemed to have failed such as anti-sense technology suddenly now provide promising results. Some initially promising therapies will need further development or have failed such as Trichuris suis ova therapy (but not helminth therapy in general), CCR9 targeted therapies or recombinant IL-10. In contrast anti-leukocate trafficking therapies appear to be quite promising. Vedolizumab is the first in class anti-integrin antibody that was approved for the therapy of CD and UC recently. Other anti-integrin antibodies and small molecule adhesion inhibitors will most likely be approved in the next years for IBD therapy. Tofacitinib, a small molecule JAK inhibitor, is a promising candidate for the treatment of UC. Phosphatidylcholine may be a future option for patients with 5-ASA refractory UC or 5-ASA intolerance. The preliminary data for Mongersen, a Smad7 antisense oligonucleotide, are promising despite some concerns about long term effect of TGFβ induction. Anti IL6 strategies will hopefully be further evaluated keeping in mind the caveat of a lack of CRP induction in anti-IL6 treated patients. Stem cell transplantation will become an option for patients that have experienced failure of established medications. Fecal microbiota transplantation and also perhaps combined probiotic therapy is a field that will be evaluated in more detail in the near future especially for UC patients. Based on these new developments treatment algorithms need to be updated. This review will reflect these current developments and give a perspective for future IBD therapy.}, }
@article {pmid26275161, year = {2015}, author = {Sun, YQ and Xu, LP and Han, TT and Zhang, XH and Wang, Y and Han, W and Wang, FR and Wang, JZ and Chen, H and Chen, YH and Yan, CH and Chen, Y and Liu, KY and Huang, XJ}, title = {Detection of human cytomegalovirus (CMV) DNA in feces has limited value in predicting CMV enteritis in patients with intestinal graft-versus-host disease after allogeneic stem cell transplantation.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {17}, number = {5}, pages = {655-661}, doi = {10.1111/tid.12420}, pmid = {26275161}, issn = {1399-3062}, mesh = {Adolescent ; Adult ; Child ; Cytomegalovirus/*isolation &amp; purification ; Cytomegalovirus Infections/complications/*diagnosis/immunology ; Enteritis/complications/*diagnosis/immunology/virology ; Feces/*virology ; Female ; Graft vs Host Disease/*complications/immunology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Immunocompromised Host ; Male ; Middle Aged ; Opportunistic Infections/complications/*diagnosis/immunology ; Retrospective Studies ; Sensitivity and Specificity ; Transplantation, Homologous ; Young Adult ; }, abstract = {BACKGROUND: Cytomegalovirus (CMV) enteritis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is difficult to diagnose. We aimed to evaluate the sensitivity and specificity of the detection of CMV DNA in feces for predicting CMV enteritis.<br><br>METHODS: HSCT patients with intestinal graft-versus-host disease (GVHD) were enrolled if they met the following criteria: (i) underwent a colonoscopy and (ii) peripheral blood and feces specimens were available for CMV DNA detection within 24 h of colonoscopy. The colonoscopy histology was used as the gold standard for diagnosing CMV enteritis.<br><br>RESULTS: Fifty-six patients underwent 58 colonoscopy examinations, and 7 were diagnosed as having CMV enteritis. Within 24 h of colonoscopy, 9 patients had detectable CMV in the feces and 19 patients had detectable CMV in the plasma, respectively. In the 7 patients with CMV enteritis, only 2 had detectable CMV in the stool, resulting in a sensitivity of 28.6%. In the 51 patients without CMV enteritis, 44 had no detectable CMV in the stool, with a specificity of 86.3%.<br><br>CONCLUSION: We concluded that CMV detection in the feces was not a good predictor of CMV enteritis in patients with intestinal GVHD after allo-HSCT.}, }
@article {pmid26274050, year = {2016}, author = {Brown, K and Godovannyi, A and Ma, C and Zhang, Y and Ahmadi-Vand, Z and Dai, C and Gorzelak, MA and Chan, Y and Chan, JM and Lochner, A and Dutz, JP and Vallance, BA and Gibson, DL}, title = {Prolonged antibiotic treatment induces a diabetogenic intestinal microbiome that accelerates diabetes in NOD mice.}, journal = {The ISME journal}, volume = {10}, number = {2}, pages = {321-332}, pmid = {26274050}, issn = {1751-7370}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Diabetes Mellitus, Type 1/drug therapy/immunology/*microbiology ; Disease Progression ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intestines/drug effects/immunology/*microbiology ; Male ; Mice ; Mice, Inbred NOD ; Th17 Cells/drug effects/immunology ; }, abstract = {Accumulating evidence supports that the intestinal microbiome is involved in Type 1 diabetes (T1D) pathogenesis through the gut-pancreas nexus. Our aim was to determine whether the intestinal microbiota in the non-obese diabetic (NOD) mouse model played a role in T1D through the gut. To examine the effect of the intestinal microbiota on T1D onset, we manipulated gut microbes by: (1) the fecal transplantation between non-obese diabetic (NOD) and resistant (NOR) mice and (2) the oral antibiotic and probiotic treatment of NOD mice. We monitored diabetes onset, quantified CD4+T cells in the Peyer's patches, profiled the microbiome and measured fecal short-chain fatty acids (SCFA). The gut microbiota from NOD mice harbored more pathobionts and fewer beneficial microbes in comparison with NOR mice. Fecal transplantation of NOD microbes induced insulitis in NOR hosts suggesting that the NOD microbiome is diabetogenic. Moreover, antibiotic exposure accelerated diabetes onset in NOD mice accompanied by increased T-helper type 1 (Th1) and reduced Th17 cells in the intestinal lymphoid tissues. The diabetogenic microbiome was characterized by a metagenome altered in several metabolic gene clusters. Furthermore, diabetes susceptibility correlated with reduced fecal SCFAs. In an attempt to correct the diabetogenic microbiome, we administered VLS#3 probiotics to NOD mice but found that VSL#3 colonized the intestine poorly and did not delay diabetes. We conclude that NOD mice harbor gut microbes that induce diabetes and that their diabetogenic microbiome can be amplified early in life through antibiotic exposure. Protective microbes like VSL#3 are insufficient to overcome the effects of a diabetogenic microbiome.}, }
@article {pmid26266767, year = {2015}, author = {Romaniszyn, M and Rozwadowska, N and Malcher, A and Kolanowski, T and Walega, P and Kurpisz, M}, title = {Implantation of autologous muscle-derived stem cells in treatment of fecal incontinence: results of an experimental pilot study.}, journal = {Techniques in coloproctology}, volume = {19}, number = {11}, pages = {685-696}, pmid = {26266767}, issn = {1128-045X}, mesh = {Adult ; Aged ; *Anal Canal/physiopathology/surgery ; Electromyography ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Middle Aged ; Myoblasts/*transplantation ; Pilot Projects ; Pressure ; Prospective Studies ; Quadriceps Muscle/cytology/surgery ; *Recovery of Function ; Transplantation, Autologous/methods ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: The aim of this study is to present results of the implantation of autologous myoblasts into the external anal sphincter (EAS) in ten patients with fecal incontinence.<br><br>METHODS: After anatomical and functional assessment of the patients' EAS, a vastus lateralis muscle open biopsy was performed. Stem cells were extracted from the biopsy specimens and cultured in vitro. Cell suspensions were then administered to the EAS. Patients were scheduled for follow-up visits in 6-week intervals. Total follow-up was 12 months.<br><br>RESULTS: All biopsy and cell implantation procedures were performed without complications. Nine of the patients completed a full 12-month follow-up. There was subjective improvement in six patients (66.7 %). In manometric examinations 18 weeks after implantation, squeeze anal pressures and high-pressure zone length increased in all patients, with particularly significant sphincter function recovery in five patients (55.6 %). Electromyographic (EMG) examination showed an increase in signal amplitude in all patients, detecting elevated numbers of propagating action potentials. Twelve months after implantation two patients experienced deterioration of continence, which was also reflected in the deterioration of manometric and EMG parameters. The remaining four patients (44.4 %) still described their continence as better than before implantation and retained satisfactory functional examination parameters.<br><br>CONCLUSIONS: Implantation of autologous myoblasts gives good short-term results not only in a subjective assessment, but also in objective functional tests. It seems that this promising technology can improve the quality of life of patients with fecal incontinence, but further study is required to achieve better and more persistent results.}, }
@article {pmid26264819, year = {2015}, author = {Petrincová, A and Valenčáková, A and Luptáková, L and Ondriska, F and Kalinová, J and Halánová, M and Danišová, O and Jarčuška, P}, title = {Molecular characterization and first report of Cryptosporidium genotypes in human population in the Slovak Republic.}, journal = {Electrophoresis}, volume = {36}, number = {23}, pages = {2925-2930}, doi = {10.1002/elps.201500230}, pmid = {26264819}, issn = {1522-2683}, mesh = {Cryptosporidiosis/epidemiology/parasitology ; Cryptosporidium/*genetics/*isolation &amp; purification/pathogenicity ; Cryptosporidium parvum/genetics/isolation &amp; purification/pathogenicity ; Feces/parasitology ; HIV Infections/parasitology ; Humans ; Immunocompromised Host ; *Phylogeny ; Polymerase Chain Reaction ; RNA, Ribosomal/genetics ; Slovakia/epidemiology ; }, abstract = {In our study, we examined 91 fecal samples from five different groups of people containing HIV patients, hemodialysis patients, kidney transplant recipients, immunocompetent humans without clinical signs, and humans with suspected cryptosporidiosis. The purpose of our study was to determine species and genotype composition of representatives of Cryptosporidium spp. using PCR analysis of small subunit ribosomal RNA gene and 60-kDa glycoprotein gene and examine their phylogenetic relationship. In HIV-positive/AIDS-infected group of patients and in hemodialysis patients, no presence of Cryptosporidium species was detected. In two kidney transplant recipients, we detected species/genotypes Cryptosporidium parvum IIaA13G1T1R1 (KT355488) and Cryptosporidium hominis IaA11G2R8 (KT355489) and in two immunocompetent patients with clinical symptoms, we identified Cryptosporidium muris and C. hominis IbA10G2T1 (KT355490). In the group of healthy immunocompetent individuals without clinical signs, we identified species/genotype C. hominis IbA11G2 (KT355491) in one sample.}, }
@article {pmid26264779, year = {2016}, author = {Kao, D and Roach, B and Park, H and Hotte, N and Madsen, K and Bain, V and Tandon, P}, title = {Fecal microbiota transplantation in the management of hepatic encephalopathy.}, journal = {Hepatology (Baltimore, Md.)}, volume = {63}, number = {1}, pages = {339-340}, doi = {10.1002/hep.28121}, pmid = {26264779}, issn = {1527-3350}, mesh = {*Fecal Microbiota Transplantation ; Hepatic Encephalopathy/*therapy ; Humans ; Male ; Middle Aged ; }, }
@article {pmid26264455, year = {2015}, author = {Costello, SP and Conlon, MA and Vuaran, MS and Roberts-Thomson, IC and Andrews, JM}, title = {Faecal microbiota transplant for recurrent Clostridium difficile infection using long-term frozen stool is effective: clinical efficacy and bacterial viability data.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {42}, number = {8}, pages = {1011-1018}, doi = {10.1111/apt.13366}, pmid = {26264455}, issn = {1365-2036}, mesh = {Adult ; Aged ; *Clostridioides difficile/pathogenicity/physiology ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Freezing ; Humans ; Male ; Microbial Viability ; Middle Aged ; Recurrence ; Retrospective Studies ; Secondary Prevention/*methods ; Specimen Handling/*methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbial transplant (FMT) for recurrent Clostridium difficile infection (rCDI) is greatly facilitated by frozen stool banks. However, the effect of frozen storage of stool for greater than 2 months on the viability of stool bacteria is unknown and the efficacy of FMT is not clear.<br><br>AIM: To evaluate the viability of bacteria in stool frozen for up to 6&#xa0;months, and the clinical efficacy of FMT with stool frozen for 2-10&#xa0;months, for the treatment of rCDI.<br><br>METHODS: Viability of six representative groups of faecal bacteria after 2 and 6&#xa0;months of storage at -80&#xa0;&#xb0;C, in normal saline (NS) or 10% glycerol were assessed by culture on plate media. The clinical outcomes of 16 consecutive patients with rCDI treated with aliquots of stool frozen in 10% glycerol and stored for 2-10&#xa0;months were also examined.<br><br>RESULTS: Viability at both 2 and 6&#xa0;months was similar to baseline, in specimens stored in 10% glycerol and at 2&#xa0;months in stool stored in NS, but was reduced by >1 log at 6&#xa0;months for Aerobes (P&#xa0;<&#xa0;0.01), total Coliforms (P&#xa0;<&#xa0;0.01) and Lactobacilli (P&#xa0;<&#xa0;0.01) in NS. Using stool frozen for 2-10&#xa0;months in 10% glycerol, the cure rate for rCDI was 88% with one FMT and 100% after repeat FMT in those who relapsed.<br><br>CONCLUSION: Stool for faecal microbial transplant to treat rCDI can be safely stored frozen in 10% glycerol for at least 6&#xa0;months without loss of clinical efficacy or viability in the six bacterial groups tested.}, }
@article {pmid26264409, year = {2015}, author = {Landy, J and Walker, AW and Li, JV and Al-Hassi, HO and Ronde, E and English, NR and Mann, ER and Bernardo, D and McLaughlin, SD and Parkhill, J and Ciclitira, PJ and Clark, SK and Knight, SC and Hart, AL}, title = {Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {12955}, pmid = {26264409}, issn = {2045-2322}, support = {/WT_/Wellcome Trust/United Kingdom ; WMNIP33458/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; WT098051/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Chronic Disease ; *Fecal Microbiota Transplantation ; Female ; Humans ; Immunity, Innate ; Male ; Metabolomics ; Middle Aged ; Pouchitis/immunology/metabolism/microbiology/*therapy ; Proton Magnetic Resonance Spectroscopy ; }, abstract = {Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and (1)H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a "healthier" pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.}, }
@article {pmid26257300, year = {2015}, author = {Rosenbaum, M and Knight, R and Leibel, RL}, title = {The gut microbiota in human energy homeostasis and obesity.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {26}, number = {9}, pages = {493-501}, pmid = {26257300}, issn = {1879-3061}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; DK64774/DK/NIDDK NIH HHS/United States ; DK30292/DK/NIDDK NIH HHS/United States ; DK078669/DK/NIDDK NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; R01 DK030292/DK/NIDDK NIH HHS/United States ; HG4872/HG/NHGRI NIH HHS/United States ; UL1TR000040/TR/NCATS NIH HHS/United States ; DK70977/DK/NIDDK NIH HHS/United States ; P30 DK026687/DK/NIDDK NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; }, mesh = {Adiposity ; Animals ; *Energy Metabolism ; *Gastrointestinal Microbiome ; Humans ; Obesity/*metabolism/*microbiology ; }, abstract = {Numerous studies of rodents suggest that the gut microbiota populations are sensitive to genetic and environmental influences, and can produce or influence afferent signals that directly or indirectly impinge on energy homeostatic systems affecting both energy balance (weight gain or loss) and energy stores. Fecal transplants from obese and lean human, and from mouse donors to gnotobiotic mice, result in adoption of the donor somatotype by the formerly germ-free rodents. Thus, the microbiota is certainly implicated in the development of obesity, adiposity-related comorbidities, and the response to interventions designed to achieve sustained weight reduction in mice. More studies are needed to determine whether the microbiota plays a similarly potent role in human body-weight regulation and obesity.}, }
@article {pmid26256908, year = {2015}, author = {Kang, DJ and Hylemon, PB and Bajaj, JS}, title = {Fecal transplant to mitigate hyperammonemia and hepatic encephalopathy in animal models.}, journal = {Annals of hepatology}, volume = {14}, number = {5}, pages = {762-763}, pmid = {26256908}, issn = {1665-2681}, mesh = {Animals ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Hepatic Encephalopathy/microbiology/*surgery ; Hyperammonemia/microbiology/*surgery ; Mice ; }, }
@article {pmid26256692, year = {2015}, author = {Ford, CD and Lopansri, BK and Gazdik, MA and Snow, GL and Webb, BJ and Konopa, KL and Petersen, FB}, title = {The clinical impact of vancomycin-resistant Enterococcus colonization and bloodstream infection in patients undergoing autologous transplantation.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {17}, number = {5}, pages = {688-694}, doi = {10.1111/tid.12433}, pmid = {26256692}, issn = {1399-3062}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteremia/diagnosis/epidemiology/*etiology/immunology ; Enterococcus/*isolation &amp; purification ; Feces/microbiology ; Female ; Gram-Positive Bacterial Infections/diagnosis/epidemiology/*etiology/immunology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Transplantation, Autologous ; *Vancomycin Resistance ; Young Adult ; }, abstract = {BACKGROUND: Although several studies have documented adverse outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, data are inadequate for patients undergoing autologous (auto-)HSCT.<br><br>METHODS: We conducted a retrospective cohort study of 300 consecutive patients receiving an auto-HSCT between 2006 and 2014. Patients had stool cultures for VRE on admission and weekly during hospitalization.<br><br>RESULTS: Thirty-six percent of patients had VRE gastrointestinal (GI) colonization and 3% developed a VRE bloodstream infection (BSI), all of whom were colonized. VRE strain typing of BSI isolates showed that some patients shared identical patterns. Rates of colonization and BSI in colonized patients were similar to simultaneous patients undergoing allo-HSCT, except that the latter had a higher rate of colonization at admission. A diagnosis of lymphoma was associated with an increased risk of colonization. VRE BSI was associated with longer lengths of stay and possibly higher costs, but no decrease in overall survival, and colonized patients had no VRE infections during the year following discharge. Repeat stool cultures in patients subsequently undergoing allo-HSCT suggested that most, if not all, VRE-positive auto-HSCT patients lose their detectable GI colonization within a few months of discharge.<br><br>CONCLUSION: VRE colonization is frequent but carries a low risk for infection in patients undergoing auto-HSCT. However, these patients can serve as reservoirs for transmission to higher risk patients. Moreover, patients may remain colonized if proceeding to an allo-HSCT shortly after auto-HSCT, potentially increasing the risk of the allogeneic procedure.}, }
@article {pmid26253555, year = {2015}, author = {Zagari, RM and Romano, M and Ojetti, V and Stockbrugger, R and Gullini, S and Annibale, B and Farinati, F and Ierardi, E and Maconi, G and Rugge, M and Calabrese, C and Di Mario, F and Luzza, F and Pretolani, S and Savio, A and Gasbarrini, G and Caselli, M}, title = {Guidelines for the management of Helicobacter pylori infection in Italy: The III Working Group Consensus Report 2015.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {47}, number = {11}, pages = {903-912}, doi = {10.1016/j.dld.2015.06.010}, pmid = {26253555}, issn = {1878-3562}, mesh = {Amoxicillin/therapeutic use ; Antacids/*therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antigens, Bacterial/analysis ; Barrett Esophagus/complications ; Bismuth/*therapeutic use ; Breath Tests ; Clarithromycin/therapeutic use ; Disease Management ; Drug Therapy, Combination ; Dyspepsia/complications ; Feces ; Gastroesophageal Reflux/complications ; Helicobacter Infections/complications/diagnosis/*drug therapy ; *Helicobacter pylori ; Italy ; Levofloxacin/therapeutic use ; Metronidazole/therapeutic use ; Proton Pump Inhibitors/*therapeutic use ; Stomach Neoplasms/*prevention &amp; control ; Urea ; }, abstract = {Knowledge on the role of Helicobacter pylori (HP) infection is continually evolving, and treatment is becoming more challenging due to increasing bacterial resistance. Since the management of HP infection is changing, an update of the national Italian guidelines delivered in 2007 was needed. In the III Working Group Consensus Report 2015, a panel of 17 experts from several Italian regions reviewed current evidence on different topics relating to HP infection. Four working groups examined the following topics: (1) "open questions" on HP diagnosis and treatment (focusing on dyspepsia, gastro-oesophageal reflux disease, non-steroidal anti-inflammatory drugs or aspirin use and extra-gastric diseases); (2) non-invasive and invasive diagnostic tests; (3) treatment of HP infection; (4) role of HP in the prevention of gastric cancer. Statements and recommendations were discussed and a consensus reached in a final plenary session held in February 2015 in Bologna. Recommendations are based on the best current evidence to help physicians manage HP infection in Italy. The guidelines have been endorsed by the Italian Society of Gastroenterology and the Italian Society of Digestive Endoscopy.}, }
@article {pmid26252119, year = {2015}, author = {Ratner, M}, title = {Microbial cocktails join fecal transplants in IBD treatment trials.}, journal = {Nature biotechnology}, volume = {33}, number = {8}, pages = {787-788}, pmid = {26252119}, issn = {1546-1696}, mesh = {Biomedical Research ; Clinical Trials as Topic ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*therapy ; }, }
@article {pmid26249024, year = {2015}, author = {Bednarska, M and Bajer, A and Welc-Falęciak, R and Pawełas, A}, title = {Cyclospora cayetanensis infection in transplant traveller: a case report of outbreak.}, journal = {Parasites &amp; vectors}, volume = {8}, number = {}, pages = {411}, pmid = {26249024}, issn = {1756-3305}, mesh = {Adult ; Anti-Infective Agents/therapeutic use ; Cyclospora/genetics/*isolation &amp; purification ; Cyclosporiasis/drug therapy/epidemiology/*parasitology ; Diarrhea/parasitology ; Disease Outbreaks ; Humans ; Immunocompromised Host ; Indonesia/epidemiology ; Kidney Transplantation/*adverse effects ; Male ; Molecular Sequence Data ; Poland/epidemiology ; RNA, Ribosomal, 18S/genetics ; *Travel ; }, abstract = {BACKGROUND: Cyclospora cayetanensis is a protozoan parasite causing intestinal infections. A prolonged course of infection is often observed in immunocompromised individuals. In Europe, less than 100 cases of C. cayetanensis infection have been reported to date, almost all of which being diagnosed in individuals after travelling abroad.<br><br>FINDINGS: We described cases of three businessmen who developed acute traveller's diarrhoea after they returned to Poland from Indonesia. One of the travellers was a renal transplant recipient having ongoing immunosuppressive treatment. In each case, acute and prolonged diarrhoea and other intestinal disorders occurred. Oocysts of C. cayetanensis were identified in faecal smears of two of the travellers (one immunosuppressed and one immunocompetent). Diagnosis was confirmed by the successful amplification of parasite DNA (18S rDNA). A co-infection with Blastocystis hominis was identified in the immunocompetent man.<br><br>CONCLUSIONS: Infection of C. cayetanensis shall be considered as the cause of prolonged acute diarrhoea in immunocompromised patients returning from endemic regions.}, }
@article {pmid26244577, year = {2015}, author = {Di Luccia, B and Crescenzo, R and Mazzoli, A and Cigliano, L and Venditti, P and Walser, JC and Widmer, A and Baccigalupi, L and Ricca, E and Iossa, S}, title = {Rescue of Fructose-Induced Metabolic Syndrome by Antibiotics or Faecal Transplantation in a Rat Model of Obesity.}, journal = {PloS one}, volume = {10}, number = {8}, pages = {e0134893}, pmid = {26244577}, issn = {1932-6203}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/classification/genetics ; Blood Glucose/metabolism ; Blotting, Western ; Cecum/drug effects/metabolism/microbiology ; Diet ; Disease Models, Animal ; Fatty Acids, Nonesterified/blood ; Fecal Microbiota Transplantation/*methods ; Fructose/administration &amp; dosage/*adverse effects/metabolism ; Glucose/metabolism ; Lipid Peroxides/metabolism ; Liver/metabolism ; Male ; Metabolic Syndrome/etiology/metabolism/*therapy ; Microbiota/drug effects/genetics ; Muscle, Skeletal/metabolism ; Obesity/etiology/metabolism/*therapy ; Protein Carbonylation ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Ribosomal, 16S/genetics ; Rats, Sprague-Dawley ; }, abstract = {A fructose-rich diet can induce metabolic syndrome, a combination of health disorders that increases the risk of diabetes and cardiovascular diseases. Diet is also known to alter the microbial composition of the gut, although it is not clear whether such alteration contributes to the development of metabolic syndrome. The aim of this work was to assess the possible link between the gut microbiota and the development of diet-induced metabolic syndrome in a rat model of obesity. Rats were fed either a standard or high-fructose diet. Groups of fructose-fed rats were treated with either antibiotics or faecal samples from control rats by oral gavage. Body composition, plasma metabolic parameters and markers of tissue oxidative stress were measured in all groups. A 16S DNA-sequencing approach was used to evaluate the bacterial composition of the gut of animals under different diets. The fructose-rich diet induced markers of metabolic syndrome, inflammation and oxidative stress, that were all significantly reduced when the animals were treated with antibiotic or faecal samples. The number of members of two bacterial genera, Coprococcus and Ruminococcus, was increased by the fructose-rich diet and reduced by both antibiotic and faecal treatments, pointing to a correlation between their abundance and the development of the metabolic syndrome. Our data indicate that in rats fed a fructose-rich diet the development of metabolic syndrome is directly correlated with variations of the gut content of specific bacterial taxa.}, }
@article {pmid26240640, year = {2015}, author = {Cestaro, G and De Rosa, M and Massa, S and Amato, B and Gentile, M}, title = {Intersphincteric anal lipofilling with micro-fragmented fat tissue for the treatment of faecal incontinence: preliminary results of three patients.}, journal = {Wideochirurgia i inne techniki maloinwazyjne = Videosurgery and other miniinvasive techniques}, volume = {10}, number = {2}, pages = {337-341}, pmid = {26240640}, issn = {1895-4588}, abstract = {Faecal incontinence is a very debilitating problem. Many techniques have been proposed to treat this condition, with controversial results. Autologous transplant of fat tissue is an established procedure used for the repair of tissue damage, and recent studies revealed the potentiality of tissue regeneration by human adipose-derived stem cells. We treated this condition with the injection, in the intersphincteric anal groove, of lipoaspirate processed by an innovative technology (Lipogems). The aim of the study was to evaluate the efficacy of Lipogems injection for the treatment of faecal incontinence. In February 2014 we treated 3 patients with faecal incontinence. The surgical procedure required three phases: lipoaspiration, processing of lipoaspirate with the Lipogems system, and injection of the obtained product in the intersphincteric anal groove. An accurate proctological examination followed at 1 week, 1 month and 6 months after treatment. Each patient reported an improved Wexner incontinence score at 1 month after the procedure. We observed an increase of resting pressure (by at least 10 mm Hg) and thickness of the internal anal sphincter respectively at ano-rectal manometry and by ultrasound (US) evaluation at the sixth month of follow-up. Our preliminary results are encouraging, but multicentric studies with longer follow-up are needed to validate this novel technique for treatment of faecal incontinence.}, }
@article {pmid26233437, year = {2015}, author = {Mizusawa, M and Doron, S and Gorbach, S}, title = {Clostridium difficile Diarrhea in the Elderly: Current Issues and Management Options.}, journal = {Drugs &amp; aging}, volume = {32}, number = {8}, pages = {639-647}, pmid = {26233437}, issn = {1179-1969}, mesh = {Aged ; Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; Diarrhea/microbiology/*therapy ; Fidaxomicin ; Humans ; Metronidazole/therapeutic use ; Recurrence ; Risk Factors ; Vancomycin/therapeutic use ; }, abstract = {Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in healthcare settings. Along with antimicrobial exposure, advanced age has been shown to be a significant risk factor for the development and recurrence of, and mortality from, CDI. The substantial burden of CDI in the elderly may be related to frequent healthcare exposure, the necessity for more medications, altered intestinal microbiota, and complicated comorbidities. A diagnosis of CDI is based on evidence of toxin, or the C. difficile organism itself, in a stool sample in the presence of clinical signs and symptoms. Only symptomatic patients should be tested for CDI, and routine surveillance or repeat testing on asymptomatic patients as a test of cure is discouraged. Antibiotic discontinuation alone can improve or resolve CDI in some patients, and concomitant use of antibiotics is associated with decreased response to CDI treatment. Metronidazole, vancomycin, and fidaxomicin are the therapeutic agents currently available for CDI, with the selection of these agents being based on disease severity, history of recurrence, and cost. The recurrence rate after initial treatment is 20-30%. The first recurrence can be treated with the same therapeutic agent and, for subsequent recurrences, vancomycin in a tapered and/or pulsed regimen is recommended. Fecal microbiota transplantation has shown remarkable effectiveness for recurrent anti-refractory CDI, although caution is advised in treating immunocompromised hosts and those with toxic megacolon. C. difficile can be transmitted directly and indirectly via contact with patients or their environment; therefore, isolation precautions should be initiated at the first suspicion of CDI. C. difficile spores can survive for a long time on environmental surfaces, and the patient's room and all equipment used in the room should be disinfected. In order to manage CDI in the elderly, timely diagnosis, appropriate treatment based on severity of illness, and effective infection control are essential.}, }
@article {pmid26230099, year = {2015}, author = {Leber, A and Viladomiu, M and Hontecillas, R and Abedi, V and Philipson, C and Hoops, S and Howard, B and Bassaganya-Riera, J}, title = {Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection.}, journal = {PloS one}, volume = {10}, number = {7}, pages = {e0134849}, pmid = {26230099}, issn = {1932-6203}, support = {HHSN272201000056C/AI/NIAID NIH HHS/United States ; }, mesh = {Clostridioides difficile/*pathogenicity ; Clostridium Infections/*immunology/microbiology ; *Immunity, Mucosal ; *Microbiota ; *Models, Biological ; }, abstract = {Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17) effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg) cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions.}, }
@article {pmid26221192, year = {2015}, author = {Bubnov, RV and Spivak, MY and Lazarenko, LM and Bomba, A and Boyko, NV}, title = {Probiotics and immunity: provisional role for personalized diets and disease prevention.}, journal = {The EPMA journal}, volume = {6}, number = {1}, pages = {14}, pmid = {26221192}, issn = {1878-5077}, abstract = {There is great interest in the interaction between diet and immune system and concomitantly in the potential of probiotic bacteria, especially given recent advances in understanding of gut microbiota effects on health in the context of microbiome research. Following our recent study on bacterial wall elasticity as a predictive measure of phagocytic cellular reactions and related outcomes, a question was raised regarding the scope of the application of these findings in various medical conditions in the context of predictive, preventive, and personalized medicine (PPPM). This summarizing review of the data describes the contributions, both observed and potential, of probiotics to the gut-brain axis and various medical conditions, including immune and atopic states, metabolic and inflammatory diseases-including liver disease and diabetes mellitus-cancer, and more. It also suggests novel insights for a number of beneficial applications of probiotics and advances in development of novel probiotic-based treatments and personalized diets, as well as application of sophisticated imaging techniques and nanobiotechnologies that can be adopted in the near future by innovative medical experts, warranting further research and practical translation.}, }
@article {pmid26217323, year = {2015}, author = {Li, M and Liang, P and Li, Z and Wang, Y and Zhang, G and Gao, H and Wen, S and Tang, L}, title = {Fecal microbiota transplantation and bacterial consortium transplantation have comparable effects on the re-establishment of mucosal barrier function in mice with intestinal dysbiosis.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {692}, pmid = {26217323}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is a promising therapy, despite some reports of adverse side effects. Bacterial consortia transplantation (BCT) for targeted restoration of the intestinal ecosystem is considered a relatively safe and simple procedure. However, no systematic research has assessed the effects of FMT and BCT on immune responses of intestinal mucosal barrier in patients. We conducted complementary studies in animal models on the effects of FMT and BCT, and provide recommendations for improving the clinical outcomes of these treatments. To establish the dysbiosis model, male BALB/c mice were treated with ceftriaxone intra-gastrically for 7 days. After that, FMT and BCT were performed on ceftriaxone-treated mice for 3 consecutive days to rebuild the intestinal ecosystem. Post-FMT and post-BCT changes of the intestinal microbial community and mucosal barrier functions were investigated and compared. Disruption of intestinal microbial homeostasis impacted the integrity of mucosal epithelial layer, resulting in increased intestinal permeability. These outcomes were accompanied by overexpression of Muc2, significant decrease of SIgA secretion, and overproduction of defensins and inflammatory cytokines. After FMT and BCT, the intestinal microbiota recovered quickly, this was associated with better reconstruction of mucosal barriers and re-establishment of immune networks compared with spontaneous recovery (SR). Although based on a short-term study, our results suggest that FMT and BCT promote the re-establishment of intestinal microbial communities in mice with antibiotic-induced dysbiosis, and contribute to the temporal and spatial interactions between microbiota and mucosal barriers. The effects of BCT are comparable to that of FMT, especially in normalizing the intestinal levels of Muc2, SIgA, and defensins.}, }
@article {pmid26215325, year = {2015}, author = {Chen, HM and Liu, XW and Sun, RJ and Fang, JY}, title = {A survey on the developmental intestinal microbiota research in China: The history, funding, and frontiers of gut bacteria.}, journal = {Journal of digestive diseases}, volume = {16}, number = {8}, pages = {421-430}, doi = {10.1111/1751-2980.12274}, pmid = {26215325}, issn = {1751-2980}, mesh = {Biomedical Research/economics/trends ; China ; Colorectal Neoplasms/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology ; Liver Diseases/microbiology ; Metabolic Syndrome/microbiology ; Research Support as Topic/statistics &amp; numerical data/trends ; }, abstract = {Up to 100 trillion bacteria are harbored in the human intestine with a mutualistic and interdependent relationship with the host during a long period of co-evolution. The so-called intestinal microbiota (IM) fulfill important metabolic tasks and the impaired stability may lead to IM-related diseases, including inflammatory bowel disease (IBD), colorectal cancer (CRC), metabolic syndrome (MS), liver diseases, and so on. Here, we review the past and development of IM research in China, including the achievements that Chinese researchers have made both in basic and clinical scientific field. Moreover, we evaluate the contributions of the National Natural Science Foundation of China (NSFC), the 973 National Basic Research Program of China (973 Program), the 863 National High Technology Research and Development Program of China (863 Program), and funds from the public health industry in the field of IM research.}, }
@article {pmid26211780, year = {2015}, author = {Dai, T and Tang, T}, title = {[Research progress of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {18}, number = {7}, pages = {733-737}, pmid = {26211780}, issn = {1671-0274}, mesh = {*Feces ; Humans ; Inflammatory Bowel Diseases ; Intestines ; *Microbiota ; }, abstract = {Intestinal microbial ecosystem is the most complex and the largest micro-ecosystem of the mammals. The use of antibiotics can lead to a lot of major changes of the flora, making the intestinal flora damaged and impacted, even developing Clostridium difficile infection. Fecal microbiota transplantation (FMT) as a special organ transplant therapy, which can rebuild the intestinal flora, has raised the clinical concerns. It has been used in the refractory Clostridium difficile, inflammatory bowel disease, irritable bowel syndrome, chronic fatigue syndrome, and some non-intestinal diseases related to the metabolic disorders. But this method of treatment has not become a normal treatment, and many clinicians and patients can not accept it. This paper reviews relevant literature in terms of origin, indications, mechanism, production process, current situation and future research, and provide a reference for the clinical application of the treatment of fecal microbiota transplantation.}, }
@article {pmid26204547, year = {2015}, author = {Moscoso, F and Simian, D and Rivera, D and Acuña, G and Quera, R}, title = {[Fecal microbiota transplantation in recurrent Clostridium difficile infection. Report of one case].}, journal = {Revista medica de Chile}, volume = {143}, number = {4}, pages = {531-535}, doi = {10.4067/S0034-98872015000400017}, pmid = {26204547}, issn = {0717-6163}, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; Diarrhea/chemically induced/therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Middle Aged ; Recurrence ; Vancomycin/therapeutic use ; }, abstract = {Fecal microbiota transplantation (FMT) has an incomparable efficacy to treat recurrent Clostridium difficile infection, with near 90% of success. We report a 57 years old woman who developed an antibiotic associated diarrhea with a positive polymerase chain reaction test for Clostridium Difficile toxin. She was successfully treated with Vancomycin trice but diarrhea recurred. Therefore a fecal microbiota transplant was performed using solid stools from a relative, diluted in saline and instilled in the distal ileon, with a good clinical response, without recurrence of diarrhea, during a 6-month follow-up.}, }
@article {pmid26203853, year = {2015}, author = {Aggarwal, R and Goel, A}, title = {Hepatitis A: epidemiology in resource-poor countries.}, journal = {Current opinion in infectious diseases}, volume = {28}, number = {5}, pages = {488-496}, doi = {10.1097/QCO.0000000000000188}, pmid = {26203853}, issn = {1473-6527}, mesh = {Cost-Benefit Analysis ; Developing Countries ; *Hepatitis A/economics/epidemiology/mortality/prevention &amp; control ; Hepatitis A Vaccines ; Humans ; Immunization Programs ; }, abstract = {PURPOSE OF REVIEW: Transmission of hepatitis A virus (HAV) infection is primarily fecal-oral. Symptomatic hepatitis, severe disease, and death are more likely to occur when infection occurs at an older age. Improvements in socioeconomic and hygienic conditions have led to a change in its epidemiology worldwide.<br><br>RECENT FINDINGS: In the last two decades, improved hygiene in several resource-poor countries has led to reduced transmission of HAV, an increase in average age at infection, and, consequently, a paradoxical increase in morbidity and mortality because of hepatitis A. In Argentina, introduction of one dose (instead of the conventional two doses, to reduce costs) of inactivated HAV vaccine at 12-month age in a universal childhood immunization program during such 'epidemiologic transition' has markedly reduced the incidence of symptomatic hepatitis A, and of fulminant hepatitis and liver transplantation caused by HAV infection. The monetary value of medical and nonmedical benefits of this strategy outweighed the expenditure on vaccination. These excellent results were possibly contingent upon a high vaccination coverage.<br><br>SUMMARY: Resource-poor countries should closely monitor the epidemiology of HAV infection and periodically undertake cost-effectiveness analyses of HAV immunization strategies. This should allow timely identification of epidemiologic transition and introduction of preventive strategies before HAV infection becomes a public health problem.}, }
@article {pmid26198302, year = {2015}, author = {Eriguchi, Y and Nakamura, K and Hashimoto, D and Shimoda, S and Shimono, N and Akashi, K and Ayabe, T and Teshima, T}, title = {Decreased secretion of Paneth cell α-defensins in graft-versus-host disease.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {17}, number = {5}, pages = {702-706}, doi = {10.1111/tid.12423}, pmid = {26198302}, issn = {1399-3062}, mesh = {Animals ; Biomarkers/metabolism ; Dysbiosis/*metabolism/microbiology ; Enzyme-Linked Immunosorbent Assay ; Feces/*chemistry/microbiology ; Female ; Gastrointestinal Microbiome ; Graft vs Host Disease/*metabolism ; Hematopoietic Stem Cell Transplantation ; Intestinal Mucosa/metabolism ; Intestines/microbiology ; LIM Domain Proteins/*metabolism ; Mice ; Mice, Inbred C57BL ; Nuclear Proteins/*metabolism ; Paneth Cells/*metabolism ; Transplantation, Homologous ; alpha-Defensins/*metabolism ; }, abstract = {BACKGROUND: Intestinal microbial ecology is actively regulated by Paneth cell-derived antimicrobial peptides, α-defensins. Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT). We previously demonstrated that Paneth cells are targeted by GVHD, and their expression of antimicrobial peptide α-defensins is impaired, leading to a loss of physiological diversity among the microflora and development of bloodstream infection. Herein, we evaluated whether fecal levels of α-defensins could be surrogate marker of intestinal dysbiosis.<br><br>METHODS: We directly measured &#x3b1;-defensin cryptdin-1 (Crp1) in fecal pellets of mice with GVHD by using a novel enzyme-linked immunosorbent assay.<br><br>RESULTS: Fecal levels of Crp1 were significantly decreased in mice with GVHD but unchanged in mice without GVHD after SCT. These were correlated with intestinal flora diversity.<br><br>CONCLUSION: We demonstrate a link between reduced secretion of Paneth cell &#x3b1;-defensins and dysbiosis of intestinal flora in GVHD. Fecal levels of &#x3b1;-defensins could be surrogate markers for intestinal microbial homeostasis.}, }
@article {pmid26198180, year = {2015}, author = {Hourigan, SK and Chen, LA and Grigoryan, Z and Laroche, G and Weidner, M and Sears, CL and Oliva-Hemker, M}, title = {Microbiome changes associated with sustained eradication of Clostridium difficile after single faecal microbiota transplantation in children with and without inflammatory bowel disease.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {42}, number = {6}, pages = {741-752}, doi = {10.1111/apt.13326}, pmid = {26198180}, issn = {1365-2036}, mesh = {Adolescent ; Child ; *Clostridioides difficile ; Clostridium Infections/*complications/*therapy ; Colonoscopy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Humans ; Inflammatory Bowel Diseases/*complications/microbiology ; Male ; Microbiota/*physiology ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S ; Recurrence ; }, abstract = {BACKGROUND: Little data are available regarding the effectiveness and associated microbiome changes of faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in children, especially in those with inflammatory bowel disease (IBD) with presumed underlying dysbiosis.<br><br>AIM: To investigate C. difficile eradication and microbiome changes with FMT in children with and without IBD.<br><br>METHODS: Children with a history of recurrent CDI (&#x2265;3 recurrences) underwent FMT via colonoscopy. Stool samples were collected pre-FMT and post-FMT at 2-10 weeks, 10-20 weeks and 6 months. The v4 hypervariable region of the 16S rRNA gene was sequenced. C. difficile toxin B gene polymerase chain reaction was performed.<br><br>RESULTS: Eight children underwent FMT for CDI; five had IBD. All had resolution of CDI symptoms. All tested had eradication of C. difficile at 10-20 weeks and 6 months post-FMT. Pre-FMT patient samples had significantly decreased bacterial richness compared with donors (P = 0.01), in those with IBD (P = 0.02) and without IBD (P = 0.01). Post-FMT, bacterial diversity in patients increased. Six months post-FMT, there was no significant difference between bacterial diversity of donors and patients without IBD; however, bacterial diversity in those with IBD returned to pre-FMT baseline. Microbiome composition at 6 months in IBD-negative patients more closely approximated donor composition compared to IBD-positive patients.<br><br>CONCLUSIONS: FMT gives sustained C. difficile eradication in children with and without IBD. FMT-restored diversity is sustained in children without IBD. In those with IBD, bacterial diversity returns to pre-FMT baseline by 6 months, suggesting IBD host-related mechanisms modify faecal microbiome diversity.}, }
@article {pmid26190060, year = {2016}, author = {Chao, HC and Yu, WL}, title = {Treatment failure of fecal microbiota transplant for pseudomembranous colitis due to coexistent cytomegalovirus colitis.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {49}, number = {4}, pages = {617-618}, doi = {10.1016/j.jmii.2015.05.021}, pmid = {26190060}, issn = {1995-9133}, mesh = {Clostridioides difficile/pathogenicity ; Cytomegalovirus ; Cytomegalovirus Infections/*complications/virology ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Middle Aged ; Treatment Failure ; }, }
@article {pmid26186212, year = {2015}, author = {Sasada, T and Hinoi, T and Saito, Y and Adachi, T and Takakura, Y and Kawaguchi, Y and Sotomaru, Y and Sentani, K and Oue, N and Yasui, W and Ohdan, H}, title = {Chlorinated Water Modulates the Development of Colorectal Tumors with Chromosomal Instability and Gut Microbiota in Apc-Deficient Mice.}, journal = {PloS one}, volume = {10}, number = {7}, pages = {e0132435}, pmid = {26186212}, issn = {1932-6203}, mesh = {Adenomatous Polyposis Coli Protein/*deficiency/genetics ; Animals ; Carcinogenesis/*drug effects/genetics/pathology ; Chlorine/*pharmacology ; Chromosomal Instability ; Clostridioides difficile/drug effects/growth &amp; development ; Clostridium perfringens/drug effects/growth &amp; development ; Colon/drug effects/microbiology/pathology ; Colonic Neoplasms/*chemically induced/genetics/microbiology/pathology ; Disease Models, Animal ; Drinking Water/*chemistry ; Enterobacteriaceae/drug effects/growth &amp; development ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Gene Expression ; Halogenation ; Humans ; Intestine, Small/drug effects/microbiology/pathology ; Male ; Mice ; Mice, Knockout ; Microsatellite Repeats ; Staphylococcus/drug effects/growth &amp; development ; }, abstract = {The gastrointestinal tract is continuously exposed to a variety of chemicals and commensal bacteria. Recent studies have shown that changes in gut microbial populations caused by chlorine or other chemicals in the drinking water influence the development of human colorectal cancer, although the mechanism of tumorigenesis in the gut epithelium is obfuscated by the diversity of microflora and complexity of the tumor microenvironment. In this regard, mouse models that recapitulate human colorectal cancer are an invaluable tool. In this study, we used two conditional adenomatous polyposis coli (Apc) knockout mouse models to investigate the effect of chlorinated water on tumorigenesis in the digestive tract. Mice with colon-specific carcinoma--caused by either chromosomal (CDX2P 9.5-NLS Cre;Apc(+/flox), abbreviated to CPC;Apc) or microsatellite (CDX2P9.5-G19Cre;Apc(flox/flox) and CDX2P9.5-G22Cre;Apc(flox/flox)) instability, respectively--were administered chlorinated (10.0 mg/L chlorine) or tap (0.7 mg/L chlorine) water and evaluated for colon polyp formation. In CPC;Apc mice given chlorinated drinking water, tumors tended to develop in the colon, whereas in those that drank tap water, tumors were mostly observed in the small intestine. There was no difference in the rate of tumor formation of CDX2P9.5-G19Cre;Apc(flox/flox) and CDX2P9.5-G22Cre;Apc(flox/flox) mice consuming chlorinated as compared to tap water, suggesting that microsatellite instability in the Apc gene does not significantly affect tumorigenesis. Chlorinated water altered the enteric environment by reducing the fecal populations of the obligatory anaerobes Clostridium perfringens and C. difficile, as well as species belonging to the Atopobium cluster, including Enterobacteriaceae and Staphylococcus sp., which was associated with colon tumorigenesis in CPC;Apc mice. These results suggest that differences in tumorigenesis among CPC;Apc mice consuming chlorinated versus tap water may be due to differences in gastrointestinal commensal populations.}, }
@article {pmid26180828, year = {2015}, author = {Stripling, J and Kumar, R and Baddley, JW and Nellore, A and Dixon, P and Howard, D and Ptacek, T and Lefkowitz, EJ and Tallaj, JA and Benjamin, WH and Morrow, CD and Rodriguez, JM}, title = {Loss of Vancomycin-Resistant Enterococcus Fecal Dominance in an Organ Transplant Patient With Clostridium difficile Colitis After Fecal Microbiota Transplant.}, journal = {Open forum infectious diseases}, volume = {2}, number = {2}, pages = {ofv078}, pmid = {26180828}, issn = {2328-8957}, support = {P30 AI027767/AI/NIAID NIH HHS/United States ; P30 AR050948/AR/NIAMS NIH HHS/United States ; UL1 TR000165/TR/NCATS NIH HHS/United States ; }, abstract = {We report the use of fecal microbiota transplantation in a single heart-kidney transplant recipient with recurrent Clostridium difficile, vancomycin-resistant Enterococcus (VRE) fecal dominance, and recurrent VRE infections. Fecal microbiota transplantation resulted in the reconstruction of a diverse microbiota with (1) reduced relative abundance of C difficile and VRE and (2) positive clinical outcome.}, }
@article {pmid26177210, year = {2015}, author = {Paik, J and Pershutkina, O and Meeker, S and Yi, JJ and Dowling, S and Hsu, C and Hajjar, AM and Maggio-Price, L and Beck, DA}, title = {Potential for using a hermetically-sealed, positive-pressured isocage system for studies involving germ-free mice outside a flexible-film isolator.}, journal = {Gut microbes}, volume = {6}, number = {4}, pages = {255-265}, pmid = {26177210}, issn = {1949-0984}, mesh = {Air ; *Animal Experimentation ; Animals ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; *Germ-Free Life ; *Housing, Animal ; Hydrostatic Pressure ; *Mice ; }, abstract = {Germ-free mice are used to examine questions about the role of the gut microbiota in development of diseases. Generally these animals are maintained in semi-rigid or flexible-film isolators to ensure their continued sterility or, if colonized with specific microbiota, to ensure that no new species are introduced. Here, we describe the use of a caging system in which individual cages are hermetically sealed and have their own filtered positive airflow. This isopositive caging system requires less space and reduces animal housing costs. By using strict sterile techniques, we kept mice germ-free in this caging system for 12 weeks. We also used this caging system and approach to conduct studies evaluating a) the stability of the microbiome in germ-free mice receiving a fecal transplant and b) the stability of dietary-induced microbiota changes in fecal-transplanted mice. As has been shown in fecal transfer studies in isolators, we found that the transferred microbiota stabilizes as early as 2 weeks post transfer although recipient microbiota did not completely recapitulate those of the donors. Interestingly, we also noted some sex effects in these studies indicating that the sex of recipients or donors may play a role in colonization of microbiota. However, a larger study will be needed to determine what role, if any, sex plays in colonization of microbiota. Based on our studies, an isopositive caging system may be utilized to test multiple donor samples for their effects on phenotypes of mice in both normal and disease states even with limited available space for housing.}, }
@article {pmid26169276, year = {2015}, author = {Seekatz, AM and Theriot, CM and Molloy, CT and Wozniak, KL and Bergin, IL and Young, VB}, title = {Fecal Microbiota Transplantation Eliminates Clostridium difficile in a Murine Model of Relapsing Disease.}, journal = {Infection and immunity}, volume = {83}, number = {10}, pages = {3838-3846}, pmid = {26169276}, issn = {1098-5522}, support = {UL1 TR000043/TR/NCATS NIH HHS/United States ; K01 GM109236/GM/NIGMS NIH HHS/United States ; P30DK034922/DK/NIDDK NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; 2L1TR00043/TR/NCATS NIH HHS/United States ; K01GM109236/GM/NIGMS NIH HHS/United States ; U19A090871//PHS HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification ; Chronic Disease/*therapy ; Clostridioides difficile/*physiology ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; Recurrence ; }, abstract = {Recurrent Clostridium difficile infection (CDI) is of particular concern among health care-associated infections. The role of the microbiota in disease recovery is apparent given the success of fecal microbiota transplantation (FMT) for recurrent CDI. Here, we present a murine model of CDI relapse to further define the microbiota recovery following FMT. Cefoperazone-treated mice were infected with C. difficile 630 spores and treated with vancomycin after development of clinical disease. Vancomycin treatment suppressed both C. difficile colonization and cytotoxin titers. However, C. difficile counts increased within 7 days of completing treatment, accompanied by relapse of clinical signs. The administration of FMT immediately after vancomycin cleared C. difficile and decreased cytotoxicity within 1 week. The effects of FMT on the gut microbiota community were detectable in recipients 1-day posttransplant. Conversely, mice not treated with FMT remained persistently colonized with high levels of C. difficile, and the gut microbiota in these mice persisted at low diversity. These results suggest that full recovery of colonization resistance against C. difficile requires the restoration of a specific community structure.}, }
@article {pmid26168477, year = {2015}, author = {Soma, G and Inagawa, H}, title = {Methods to Prevent or Treat Refractory Diseases by Focusing on Intestinal Microbes Using LPS and Macrophages.}, journal = {Anticancer research}, volume = {35}, number = {8}, pages = {4393-4396}, pmid = {26168477}, issn = {1791-7530}, mesh = {Anti-Bacterial Agents/pharmacology ; Clostridioides difficile/immunology ; Clostridium Infections/immunology/therapy ; Colitis/therapy ; Enterocolitis, Pseudomembranous/therapy ; Gram-Negative Bacteria/*immunology ; Humans ; Intestines/immunology/*microbiology ; Lipopolysaccharides/immunology ; Macrophage Activation/*immunology ; Macrophages/*immunology ; Microbiota/*immunology ; Neoplasms/*drug therapy/*immunology ; Vancomycin-Resistant Enterococci/drug effects/immunology ; }, abstract = {Intestinal microbes are known to influence host homeostasis by producing various substances. Recently, the presence of a diverse range of intestinal microbiota has been shown to play a key role in the maintenance of health, along with influencing the host's innate immunity towards various diseases. For example, fecal microbiota transplantation (FMT) from healthy individuals was remarkably effective in cases of refractory Clostridium difficile colitis. Conversely, decreased number of intestinal microbes resulting from the oral administration of antibiotics reportedly suppressed the antitumor effects of immunotherapy or anticancer drugs. Furthermore, it has been shown that a change in the intestinal environment triggered by oral administration of antibiotics resulted in increased number of drug-resistant microbes causing nosocomial infections. Intestinal microbes are also shown to be effective in cancer treatment as they activate macrophages at the site of cancer. One of the effects of intestinal microbes on hosts that has been gaining increasing attention is the biological regulation caused by the lipopolysaccharides (LPS) produced by Gram-negative bacteria. Among the intestinal microbiota present in the host, Gram-negative bacteria form the most dominant flora. The administration of antibiotics leads to a decreased number of intestinal microbes, as well as to suppression of cancer immunotherapy effects or anticancer drug effects, and this deterioration has been shown to be improved by oral administration of LPS. In this article, we discuss the functions of intestinal microbiota, that is currently undergoing a paradigm shift in relation to maintenance of health and the validity of LPS as a possible target for bio-treatment in the future.}, }
@article {pmid26167092, year = {2015}, author = {Mishima, K and Obara, H and Sugita, K and Shinoda, M and Kitago, M and Abe, Y and Hibi, T and Yagi, H and Matsubara, K and Mori, T and Takano, Y and Fujiwara, H and Itano, O and Hasegawa, N and Iwata, S and Kitagawa, Y}, title = {Helicobacter cinaedi bacteremia with cellulitis after ABO-incompatible living-donor liver transplantation: Case report.}, journal = {World journal of gastroenterology}, volume = {21}, number = {25}, pages = {7911-7915}, pmid = {26167092}, issn = {2219-2840}, mesh = {ABO Blood-Group System/*immunology ; Animals ; Anti-Bacterial Agents/therapeutic use ; Blood Group Incompatibility/*immunology ; Cellulitis/diagnosis/drug therapy/immunology/*microbiology ; Dogs/microbiology ; Feces/microbiology ; Helicobacter Infections/diagnosis/drug therapy/immunology/*microbiology/transmission ; *Histocompatibility ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/adverse effects ; Liver Transplantation/*adverse effects/methods ; *Living Donors ; Male ; Middle Aged ; Opportunistic Infections/diagnosis/drug therapy/immunology/*microbiology/transmission ; Risk Factors ; Treatment Outcome ; Zoonoses ; }, abstract = {Helicobacter cinaedi (H. cinaedi), a Gram-negative spiral-shaped bacterium, is an enterohepatic non-Helicobacter pylori Helicobacter species. We report the first case of H. cinaedi bacteremia with cellulitis after liver transplantation. A 48-year-old male, who had been a dog breeder for 15 years, underwent ABO-incompatible living-donor liver transplantation for hepatitis C virus-induced decompensated cirrhosis using an anti-hepatitis B core antibody-positive graft. The patient was preoperatively administered rituximab and underwent plasma exchange twice to overcome blood type incompatibility. After discharge, he had been doing well with immunosuppression therapy comprising cyclosporine, mycophenolate mofetil, and steroid according to the ABO-incompatible protocol of our institution. However, 7 mo after transplantation, he was admitted to our hospital with a diagnosis of recurrent cellulitis on the left lower extremity, and H. cinaedi was detected by both blood culture and polymerase chain reaction analysis. Antibiotics improved his symptoms, and he was discharged at day 30 after admission. Clinicians should be more aware of H. cinaedi in immunocompromised patients, such as ABO-incompatible transplant recipients.}, }
@article {pmid26165093, year = {2015}, author = {Pariente, A}, title = {[Significant weight gain after fecal transplantation: a disturbing clinical case].}, journal = {La Revue du praticien}, volume = {65}, number = {5}, pages = {623}, pmid = {26165093}, issn = {0035-2640}, }
@article {pmid26164767, year = {2015}, author = {Sheahan, A and Copeland, G and Richardson, L and McKay, S and Chou, A and Babady, NE and Tang, YW and Boulad, F and Eagan, J and Sepkowitz, K and Kamboj, M}, title = {Control of norovirus outbreak on a pediatric oncology unit.}, journal = {American journal of infection control}, volume = {43}, number = {10}, pages = {1066-1069}, pmid = {26164767}, issn = {1527-3296}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Caliciviridae Infections/diagnosis/*epidemiology/prevention &amp; control ; Child ; Child, Preschool ; Cross Infection/diagnosis/*epidemiology/prevention &amp; control ; *Disease Outbreaks ; Disease Transmission, Infectious/*prevention &amp; control ; Feces/virology ; Female ; Hospitals, Pediatric ; Humans ; Infant ; Infection Control/*methods ; Male ; Molecular Diagnostic Techniques ; Norovirus/*isolation &amp; purification ; *Oncology Service, Hospital ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Patients undergoing treatment for cancer with chemotherapy and hematopoietic stem cell recipients are at risk for severe morbidity caused by norovirus (NV).<br><br>METHODS: We describe a NV outbreak on the Memorial Sloan Kettering Cancer Center's pediatric oncology unit. Stool testing for diagnosis of NV was performed by real-time polymerase chain reaction (PCR).<br><br>RESULTS: Twelve NV cases occurred; 7 were hospital acquired. Twenty-five health care workers reported NV compatible illness. Patient-to-patient transmission occurred once. The practices of the Centers for Disease Control and Prevention were supplemented with electronic surveillance, surrogate screening for NV, and heightened cleaning. Two additional cases occurred after implementation of interventions. Long-term shedding was detected in 2 patients.<br><br>CONCLUSION: We describe interventions for controlling NV on a pediatric oncology unit. High-risk chronic shedders pose ongoing transmission risks. PCR is a valuable diagnostic tool but may be overly sensitive. Surrogate markers to assess NV burden in stool and studies on NV screening are needed to develop guidelines for high-risk chronic shedders.}, }
@article {pmid26163107, year = {2015}, author = {Tacke, D and Wisplinghoff, H and Kretzschmar, A and Farowski, F and Koehler, P and Herweg, J and Cornely, OA and Vehreschild, MJ}, title = {First implementation of frozen, capsulized faecal microbiota transplantation for recurrent Clostridium difficile infection into clinical practice in Europe.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {21}, number = {11}, pages = {e82-4}, doi = {10.1016/j.cmi.2015.06.027}, pmid = {26163107}, issn = {1469-0691}, mesh = {Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Enterocolitis/microbiology/*therapy ; Europe ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Middle Aged ; Recurrence ; Treatment Outcome ; }, }
@article {pmid26159166, year = {2015}, author = {Wei, Y and Gong, J and Zhu, W and Guo, D and Gu, L and Li, N and Li, J}, title = {Fecal microbiota transplantation restores dysbiosis in patients with methicillin resistant Staphylococcus aureus enterocolitis.}, journal = {BMC infectious diseases}, volume = {15}, number = {}, pages = {265}, pmid = {26159166}, issn = {1471-2334}, mesh = {Adult ; Child ; Combined Modality Therapy ; Cross Infection/drug therapy ; Dysbiosis/microbiology/*therapy ; Enterocolitis/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Methicillin Resistance/drug effects ; *Methicillin-Resistant Staphylococcus aureus/growth &amp; development ; Middle Aged ; Staphylococcal Infections/microbiology/*therapy ; Vancomycin/therapeutic use ; Young Adult ; }, abstract = {BACKGROUND: Nosocomial Methicillin-resistant Staphylococcus aureus (MRSA) enteritis is rare but can be fatal unless it is detected at an early stage and treated effectively. Dysbiosis of the gut is one of the leading reasons of MRSA enteritis. Fecal microbiota transplantation (FMT) is a burgeoning treatment to rectify this imbalance. But the impact of FMT on MRSA enterocoitis is still unknown yet.<br><br>METHODS: A total of 5 patients diagnosed as MRSA enteritis during the early postoperative period were given vancomycin 2 g/day for 3 days and FMT for three continuous days as a standard treatment.<br><br>RESULT: There was a 100% clinical response rate that all the symptoms resulting from MRSA enterocolitis disappeared and MRSA in the feces eliminated clearly. The microbiota profile in feces of the patients also regained balance.<br><br>CONCLUSION: FMT can be a preferential measure to restore the dysbiosis caused by MSRA enterocolitis.}, }
@article {pmid26154556, year = {2015}, author = {Ganc, AJ and Ganc, RL and Reimão, SM and Frisoli Junior, A and Pasternak, J}, title = {Fecal microbiota transplant by push enteroscopy to treat diarrhea caused by Clostridium difficile.}, journal = {Einstein (Sao Paulo, Brazil)}, volume = {13}, number = {2}, pages = {338-339}, pmid = {26154556}, issn = {2317-6385}, mesh = {Aged, 80 and over ; *Clostridioides difficile ; Diarrhea/microbiology/*therapy ; Endoscopes, Gastrointestinal/*standards ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Humans ; Male ; *Microbiota ; Recurrence ; Transplantation, Homologous/methods ; Treatment Outcome ; }, abstract = {Clostridium difficile is the major etiological agent of pseudomembranous colitis and is found in up to 20% of adult inpatients. The recommended treatment is antibiotic therapy with metronidazole and/or vancomycin. However, the recurrence rate may reach up to 25% and it increases in each episode. The newest alternative to treat diarrhea due to recurrent Clostridium difficile is fecal microbiota transplantation. The procedure was performed in 12 patients, with a 6-month follow-up on 10 of them. Of the ten cases, bacterial recurrence was diagnosed in only one patient, after a course of antibiotic to treat urinary tract infection, without presenting with diarrhea. The particularity of our study, besides being an unprecedented event in South America, is the way to perform the infusion of fecal microbiota by enteroscopy.}, }
@article {pmid26153514, year = {2016}, author = {Almeida, R and Gerbaba, T and Petrof, EO}, title = {Recurrent Clostridium difficile infection and the microbiome.}, journal = {Journal of gastroenterology}, volume = {51}, number = {1}, pages = {1-10}, pmid = {26153514}, issn = {1435-5922}, mesh = {*Clostridioides difficile ; Dysbiosis/complications ; Enterocolitis, Pseudomembranous/*microbiology/therapy ; Fecal Microbiota Transplantation/adverse effects/methods ; *Gastrointestinal Microbiome ; Humans ; Recurrence ; Risk Factors ; }, abstract = {The diverse and densely populated gastrointestinal microbiota is essential for the regulation of host physiology and immune function. As our knowledge of the composition and function of the intestinal microbiota continues to expand, there is new interest in using these developments to tailor fecal microbiota transplantation (FMT) and microbial ecosystem therapeutics (MET) for a variety of diseases. The potential role of FMT and MET in the treatment of Clostridium difficile infection (CDI)-currently the leading nosocomial gastrointestinal infection-has proven highly effective for recurrent CDI, and has emerged as a paradigm shift in the treatment of this disease. The current review will serve as a summary of the key aspects of CDI, and will introduce the essential framework and challenges of FMT, as is currently practiced. MET represents the progression of conventional bacteriotherapy that fundamentally capitalizes on the restorative properties of intestinal bacterial communities and may be viewed as the culmination of a rationally designed therapeutic modality. As our understanding of the composition and function of the intestinal microbiota evolves, it will likely drive next-generation microbiota therapies for a range of medical conditions, such as inflammatory bowel disease, obesity, and metabolic syndrome.}, }
@article {pmid26153295, year = {2015}, author = {Gupta, A and Khanna, S}, title = {Ipilimumab-associated colitis or refractory Clostridium difficile infection?.}, journal = {BMJ case reports}, volume = {2015}, number = {}, pages = {}, pmid = {26153295}, issn = {1757-790X}, mesh = {Aged ; Anti-Inflammatory Agents/*administration &amp; dosage ; Antibodies, Monoclonal/*administration &amp; dosage/adverse effects ; Clostridioides difficile/*drug effects ; Colitis/chemically induced/complications/*drug therapy ; Diarrhea/drug therapy/*etiology ; Enterocolitis, Pseudomembranous/complications/*drug therapy ; Fluid Therapy/methods ; Humans ; Ipilimumab ; Male ; Methylprednisolone/*administration &amp; dosage ; Treatment Outcome ; }, abstract = {We present a case of a patient with a diagnostic dilemma who was referred for possible faecal microbiota transplantation (FMT) for refractory diarrhoea secondary to Clostridium difficile infection (CDI). On detailed history, the patient was exposed to ipilimumab concomitantly while being treated for CDI, and was instead diagnosed with diarrhoea secondary to superimposed ipilimumab-associated colitis. Ipilimumab is an anti-CTLA4 monoclonal antibody approved for use in metastatic melanoma and under trial for other indications. Ipilimumab is associated with several immune-related adverse effects, of which diarrhoea and colitis are the most common. While FMT has shown tremendous efficacy in managing recurrent and refractory CDI, it was not offered in this case due to negative C. difficile testing showing a high degree of suspicion for ipilimumab-associated colitis due to recent drug use. Our patient was successfully managed with fluid resuscitation and steroids, and remains symptom free at last follow-up at 9 months.}, }
@article {pmid26147207, year = {2015}, author = {Montassier, E and Gastinne, T and Vangay, P and Al-Ghalith, GA and Bruley des Varannes, S and Massart, S and Moreau, P and Potel, G and de La Cochetière, MF and Batard, E and Knights, D}, title = {Chemotherapy-driven dysbiosis in the intestinal microbiome.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {42}, number = {5}, pages = {515-528}, doi = {10.1111/apt.13302}, pmid = {26147207}, issn = {1365-2036}, mesh = {Actinobacteria/drug effects ; Adult ; Antineoplastic Agents/*adverse effects/therapeutic use ; Dysbiosis/chemically induced/metabolism/microbiology ; Feces/microbiology ; Female ; Firmicutes/drug effects ; Gastrointestinal Microbiome/drug effects ; Hematopoietic Stem Cell Transplantation/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Lymphoma, Non-Hodgkin/*drug therapy/therapy ; Male ; Middle Aged ; Mucositis/*chemically induced/*metabolism/microbiology ; Proteobacteria/drug effects ; RNA, Ribosomal, 16S/*drug effects/metabolism ; }, abstract = {BACKGROUND: Chemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation (HSCT). Chemotherapy leads to several side effects, with gastrointestinal (GI) mucositis being one of the most frequent. Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome.<br><br>AIM: To identify functional mechanisms by which the intestinal microbiome may play a key role in the pathophysiology of GI mucositis, we applied high-throughput DNA-sequencing analysis to identify microbes and microbial functions that are modulated following chemotherapy.<br><br>METHODS: We amplified and sequenced 16S rRNA genes from faecal samples before and after chemotherapy in 28 patients with non-Hodgkin's lymphoma who received the same myeloablative conditioning regimen and no other concomitant therapy such as antibiotics.<br><br>RESULTS: We found that faecal samples collected after chemotherapy exhibited significant decreases in abundances of Firmicutes (P&#xa0;=&#xa0;0.0002) and Actinobacteria (P&#xa0;=&#xa0;0.002) and significant increases in abundances of Proteobacteria (P&#xa0;= 0.0002) compared to samples collected before chemotherapy. Following chemotherapy, patients had reduced capacity for nucleotide metabolism (P&#xa0;=&#xa0;0.0001), energy metabolism (P&#xa0;=&#xa0;0.001), metabolism of cofactors and vitamins (P&#xa0;=&#xa0;0.006), and increased capacity for glycan metabolism (P&#xa0;= 0.0002), signal transduction (P&#xa0;=&#xa0;0.0002) and xenobiotics biodegradation (P&#xa0;=&#xa0;0.002).<br><br>CONCLUSIONS: Our study identifies a severe compositional and functional imbalance in the gut microbial community associated with chemotherapy-induced GI mucositis. The functional pathways implicated in our analysis suggest potential directions for the development of intestinal microbiome-targeted interventions in cancer patients.}, }
@article {pmid26146498, year = {2015}, author = {Wei, Y and Zhu, W and Gong, J and Guo, D and Gu, L and Li, N and Li, J}, title = {Fecal Microbiota Transplantation Improves the Quality of Life in Patients with Inflammatory Bowel Disease.}, journal = {Gastroenterology research and practice}, volume = {2015}, number = {}, pages = {517597}, pmid = {26146498}, issn = {1687-6121}, abstract = {Introduction. To determine the effect of fecal microbiota transplantation (FMT) on quality of life (QoL) in patients with inflammatory bowel disease (IBD). Methods. Fourteen IBD patients, including 11 Ulcerative colitis (UC) and 3 Crohn's disease (CD), were treated with FMT via colonoscopy or nasojejunal tube infusion. QoL was measured by IBD Questionnaire (IBDQ). Disease activity and IBDQ were evaluated at enrollment and four weeks after treatment. Patients' attitude concerning the treatment was also investigated. Results. One patient was excluded due to intolerance. All the other patients finished the study well. Mean Mayo score in UC patients decreased significantly (5.80 ± 1.87 versus 1.50 ± 1.35, P < 0.01). Mean IBDQ scores of both UC and CD patients increased (135.50 ± 27.18 versus 177.30 ± 20.88, P = 0.00063, and 107.33 ± 9.45 versus 149.00 ± 20.07, P = 0.024) four weeks after fecal microbiota transplantation. There was no correlation between the IBDQ score and Mayo score before and after FMT. Patients refused to take FMT as treatment repeatedly in a short time. Conlusions. Fecal microbiota transplantation improves quality of life significantly in patients with inflammatory bowel disease.}, }
@article {pmid26141116, year = {2016}, author = {Han, S and Shannahan, S and Pellish, R}, title = {Fecal Microbiota Transplant: Treatment Options for Clostridium difficile Infection in the Intensive Care Unit.}, journal = {Journal of intensive care medicine}, volume = {31}, number = {9}, pages = {577-586}, doi = {10.1177/0885066615594344}, pmid = {26141116}, issn = {1525-1489}, mesh = {Aminoglycosides/*therapeutic use ; Anti-Infective Agents/*therapeutic use ; Clostridioides difficile/isolation &amp; purification/*pathogenicity ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Fidaxomicin ; Humans ; *Intensive Care Units ; Practice Guidelines as Topic ; Randomized Controlled Trials as Topic ; Recurrence ; Rifamycins/*therapeutic use ; Rifaximin ; Treatment Outcome ; }, abstract = {Clostridium difficile infection (CDI) has steadily increased in incidence since the 1990s, with an associated increase in recurrence and severity, which has in turn lead to more intensive care unit (ICU) admissions. The development of recurrent CDI, in particular, has been associated with increasing patient morbidity and mortality as well as an immense financial burden on the health care system. Recently, fecal microbiota transplantation (FMT) has received much publicity as an effective means of treatment for recurrent CDI. The goal of this review is to provide evidence-based recommendations for the diagnosis and management of CDI, with a particular focus on FMT and its utilization in the ICU.}, }
@article {pmid26140631, year = {2015}, author = {Ponte, A and Pinho, R and Mota, M and Silva, J and Vieira, N and Oliveira, R and Pinto-Pais, T and Fernandes, C and Ribeiro, I and Rodrigues, J and Lopes, P and Teixeira, T and Carvalho, J}, title = {Initial experience with fecal microbiota transplantation in Clostridium difficile infection - transplant protocol and preliminary results.}, journal = {Revista espanola de enfermedades digestivas}, volume = {107}, number = {7}, pages = {402-407}, doi = {10.17235/reed.2015.3767/2015}, pmid = {26140631}, issn = {1130-0108}, mesh = {Aged ; Aged, 80 and over ; Clinical Protocols ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Colonoscopy ; Endoscopy, Digestive System ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Clostridium difficile infection (CDI) constitutes an important cause of antibiotic-associated diarrhea. Recurrence after first-line treatment with antibiotics is high and fecal microbiota transplantation (FMT) may be effective for refractory and recurrent CDI. This series aims to describe the efficacy of FMT in the treatment of refractory and recurrent CDI.<br><br>METHODS: A prospectively recorded single-centre case series of patients with persistent or recurrent CDI treated with FMT between June 2014 and March 2015 was analyzed. Primary and secondary outcomes were defined as resolution of diarrhea without recurrence of CDI within 2 months after one or more FMT, respectively. A descriptive analysis was performed.<br><br>RESULTS: 8 FMT were performed in 6 patients, 3 with refractory CDI and 3 with recurrent CDI. The median age of recipients was 71 years and 66.7% were women. One FMT was delivered through colonoscopy and the remaining 87.5% through esophagogastroduodenoscopy. One upper FMT was excluded due to recurrence of CDI after antibiotic exposure for a respiratory infection. The overall cure rate of FMT was total with lower route and 83.3% with upper route. Primary cure rate was achieved in 83.3% of patients and secondary cure rate was achieved in all patients. Median time to resolution of diarrhea after FMT was 1 day and no complications were reported during follow-up.<br><br>CONCLUSION: FMT appears to constitute a safe and effective approach in the management of refractory and recurrent CDI. Difference between primary and secondary cure rates may result of insufficient restoration of intestinal microbiota with a single FMT.}, }
@article {pmid26140630, year = {2015}, author = {Ferre-Aracil, C and Aguilera-Castro, L and Rodríguez-de-Santiago, E and García-García-de-Paredes, A and López-Sanromán, A}, title = {Fecal microbiota transplantation - something more than merely a therapeutic curiosity.}, journal = {Revista espanola de enfermedades digestivas}, volume = {107}, number = {7}, pages = {399-401}, doi = {10.17235/reed.2015.3875/2015}, pmid = {26140630}, issn = {1130-0108}, mesh = {Clostridium Infections/microbiology/*therapy ; Crohn Disease/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Obesity/microbiology/*therapy ; Treatment Outcome ; }, }
@article {pmid26133188, year = {2015}, author = {Belmaáti, MS and Claesson, MH}, title = {Depletion of enteroantigen-activated CD4[+] T cells: effects on proliferation and pathogenicity.}, journal = {International immunology}, volume = {27}, number = {9}, pages = {419-424}, doi = {10.1093/intimm/dxv039}, pmid = {26133188}, issn = {1460-2377}, mesh = {Animals ; Antigen-Presenting Cells/immunology ; Antigens, Bacterial/immunology ; CD4-Positive T-Lymphocytes/*immunology ; Cell Proliferation/*physiology ; Colitis/immunology ; Female ; Lymphocyte Activation/*immunology ; Lymphocyte Depletion/methods ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; T-Lymphocytes, Regulatory/immunology ; Virulence/*immunology ; }, abstract = {Naive CD4(+) T cells depleted of natural Treg (CD25(+)) cells proliferate extensively when exposed to a fecal extract [enteroantigen (eAg)] pulsed on antigen-presenting cells (APC). When transplanted into SCID recipient mice, the CD25-depleted T cells induce a chronic colitis with a lethal course. We observed here that if T cells, pre-activated for 48h by eAg from BALB/c or SCID mice, are removed and then reexposed to either of the two sources of antigen, these T cells have completely lost their anti-eAg proliferative capacity in vitro. This observation indicates that eAgs derived from Balb/c and SCID mice are recognized by similar subsets of T cells. However, when transferred into SCID mice, eAg-activation-depleted T cells are still capable of inducing a severe colitis fully comparable with the disease induced by naive CD4(+) T cells.}, }
@article {pmid26125460, year = {2016}, author = {Aroniadis, OC and Brandt, LJ and Greenberg, A and Borody, T and Kelly, CR and Mellow, M and Surawicz, C and Cagle, L and Neshatian, L and Stollman, N and Giovanelli, A and Ray, A and Smith, R}, title = {Long-term Follow-up Study of Fecal Microbiota Transplantation for Severe and/or Complicated Clostridium difficile Infection: A Multicenter Experience.}, journal = {Journal of clinical gastroenterology}, volume = {50}, number = {5}, pages = {398-402}, doi = {10.1097/MCG.0000000000000374}, pmid = {26125460}, issn = {1539-2031}, mesh = {Abdominal Pain/etiology ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Diarrhea/microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Severity of Illness Index ; Surveys and Questionnaires ; Time Factors ; Treatment Outcome ; }, abstract = {GOAL: Our aim was to investigate fecal microbiota transplantation (FMT) efficacy in patients with severe and/or complicated Clostridium difficile infection (CDI).<br><br>BACKGROUND: FMT is successful for recurrent CDI, although its benefit in severe or complicated CDI has not specifically been evaluated.<br><br>STUDY METHODS: A multicenter long-term follow-up study was performed in patients who received FMT for severe and/or complicated CDI (diagnosed using standard criteria). Pre-FMT and post-FMT questionnaires were completed. Study outcomes included cure rates and time to resolution of symptoms.<br><br>RESULTS: A total of 17 patients (82% inpatients, 18% outpatients) were included (76.4% women; mean age, 66.4 y; mean follow-up, 11.4 mo). Patients had severe and complicated (76.4%) or either severe or complicated (23.6%) CDI. Sixteen patients (94.1%) had diarrhea, which resolved in 12 (75%; mean time to resolution, 5.7 d) and improved in 4 (25%) after FMT. Eleven patients (64.7%) had abdominal pain, which resolved in 8 (72.7%; mean time to resolution, 9.6 d) and improved in 3 (27.3%) after FMT. Two of 17 patients experienced early CDI recurrence (&#x2264;90 d) after FMT (primary cure rate, 88.2%); and in 1 patient, a second FMT resulted in cure (secondary cure rate, 94.1%). Late CDI recurrence (&#x2265;90 d) was seen in 1 of 17 patients (5.9%) in association with antibiotics and was successfully treated with a repeat FMT. No adverse effects directly related to FMT occurred.<br><br>CONCLUSIONS: FMT was successful and safe in this cohort of patients with severe or complicated CDI. Primary and secondary cure rates were 88.2% and 94.1%, respectively.}, }
@article {pmid26124989, year = {2015}, author = {Hur, KY and Lee, MS}, title = {Gut Microbiota and Metabolic Disorders.}, journal = {Diabetes &amp; metabolism journal}, volume = {39}, number = {3}, pages = {198-203}, pmid = {26124989}, issn = {2233-6079}, abstract = {Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders.}, }
@article {pmid26123364, year = {2015}, author = {Liang, L and Ai, L and Qian, J and Fang, JY and Xu, J}, title = {Long noncoding RNA expression profiles in gut tissues constitute molecular signatures that reflect the types of microbes.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {11763}, pmid = {26123364}, issn = {2045-2322}, mesh = {Animals ; Binding Sites ; *Gastrointestinal Microbiome ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Molecular Sequence Annotation ; RNA, Long Noncoding/genetics/*metabolism ; *Transcriptome ; Zebrafish ; }, abstract = {The gut microbiota is commonly referred to as a hidden organ due to its pivotal effects on host physiology, metabolism, nutrition and immunity. The gut microbes may be shaped by environmental and host genetic factors, and previous studies have focused on the roles of protein-coding genes. Here we show a link between long non-coding RNA (lncRNA) expression and gut microbes. By repurposing exon microarrays and comparing the lncRNA expression profiles between germ-free, conventional and different gnotobiotic mice, we revealed subgroups of lncRNAs that were specifically enriched in each condition. A nearest shrunken centroid methodology was applied to obtain lncRNA-based signatures to identify mice in different conditions. The lncRNA-based prediction model successfully identified different gnotobiotic mice from conventional and germ-free mice, and also discriminated mice harboring transplanted microbes from fecal samples of mice or zebra fishes. To achieve optimal prediction accuracy, fewer lncRNAs were required in the prediction model than protein-coding genes. Taken together, our study demonstrated the effecacy of lncRNA expression profiles in discriminating the types of microbes in the gut. These results also provide a resource of gut microbe-associated lncRNAs for the development of lncRNA biomarkers and the identification of functional lncRNAs in host-microbes interactions.}, }
@article {pmid26113167, year = {2015}, author = {Marra, F and Ng, K}, title = {Controversies Around Epidemiology, Diagnosis and Treatment of Clostridium difficile Infection.}, journal = {Drugs}, volume = {75}, number = {10}, pages = {1095-1118}, pmid = {26113167}, issn = {1179-1950}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; *Enterocolitis, Pseudomembranous/diagnosis/drug therapy/epidemiology/therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Fidaxomicin ; Humans ; Incidence ; Metronidazole/therapeutic use ; Molecular Diagnostic Techniques ; Polymerase Chain Reaction ; Probiotics/*therapeutic use ; Recurrence ; Risk Factors ; Vancomycin/therapeutic use ; }, abstract = {Clostridium difficile infection is a major public health problem. However, in recent years the epidemiology, risk factors, diagnosis, and treatment of C. difficile infection have undergone a significant change. The incidence of C. difficile has increased, not only in the healthcare sector but also in the community. Hospital-acquired infection and community-acquired disease have different risk factors, with the latter occurring in children and younger individuals without a history of antibiotic use or previous infections. From a clinician's perspective, a quick efficient diagnosis is required for patient treatment; however, the old method of using enzyme immunoassays is insensitive and not very specific. Recent literature around diagnostic testing for C. difficile infection suggests using PCR or a two-step algorithm to improve sensitivity and specificity. More failures and recurrence with metronidazole have led to treatment algorithms suggesting its use for mild infections and switching to vancomycin if there is no clinical improvement. Alternatively, if signs and symptoms suggest severe infection, then oral vancomycin is recommended as a first-line agent. The addition of a new but costly agent, fidaxomicin, has seen some disparity between the European and North American guidelines with regard to when it should be used. Lastly, rapid developments and good results with fecal microbial transplantation have also left clinicians wondering about its place in therapy. This article reviews the literature around some of the recent controversies in the field of C. difficile infection.}, }
@article {pmid26110044, year = {2015}, author = {Мokrozub, VV and Lazarenko, LM and Sichel, LM and Babenko, LP and Lytvyn, PM and Demchenko, OM and Melnichenko, YO and Boyko, NV and Biavati, B and DiGioia, D and Bubnov, RV and Spivak, MY}, title = {The role of beneficial bacteria wall elasticity in regulating innate immune response.}, journal = {The EPMA journal}, volume = {6}, number = {1}, pages = {13}, pmid = {26110044}, issn = {1878-5077}, abstract = {BACKGROUND: Probiotics have great potential to contribute to development of healthy dietary regimes, preventive care, and an integrated approach to immunity-related disease management. The bacterial wall is a dynamic entity, depending on many components and playing an essential role in modulating immune response. The impact of cell wall elasticity on the beneficial effects of probiotic strains has not been sufficiently studied. The aim was to investigate the effect of lactic acid bacteria (LAB) and bifidobacteria strains on phagocytic system cells (macrophages) as related to bacterial wall elasticity, estimated using atomic force microscopy (AFM).<br><br>METHODS: We conducted studies on Balb/c line mice 18-20 g in weight using lyophilized strains of LAB-Lactobacillus acidophilus IMV B-7279, Lactobacillus casei IMV B-7280, Lactobacillus delbrueckii subsp. bulgaricus IMV B-7281, and bifidobacteria-Bifidobacterium animalis VKL and Bifidobacterium animalis VKB. We cultivated the macrophages obtained from the peritoneal cavity of mice individually with the strains of LAB and bifidobacteria and evaluated their effect on macrophages, oxygen-dependent bactericidal activity, nitric oxide production, and immunoregulatory cytokines. We used AFM scanning to estimate bacterial cell wall elasticity.<br><br>RESULTS: All strains had a stimulating effect on the functional activity of macrophages and ability to produce NO/NO2 in vitro. Lactobacilli strains increased the production of IL-12 and IFN-&#x3b3; in vitro. The AFM demonstrated different cell wall elasticity levels in various strains of LAB and bifidobacteria. The rigidity of the cell walls among lactobacilli was distributed as follows: Lactobacillus acidophilus IMV B-7279 > Lactobacillus casei IMV B-7280 > Lactobacillus delbrueckii subsp. bulgaricus IMV B-7281; among the strains of bifidobacteria: B. animalis VKB > B. animalis VKL. Probiotic strain survival in the macrophages depended on the bacterial cell wall elasticity and on the time of their joint cultivation.<br><br>CONCLUSION: LAB and bifidobacteria strains stimulate immune-modulatory cytokines and active oxygen and nitrogen oxide compound production in macrophages. Strains with a more elastic cell wall according to AFM data demonstrated higher resistance to intracellular digestion in macrophages and higher level of their activation. AFM might be considered as a fast and accurate method to assess parameters of probiotic strain cell wall to predict their immune-modulatory properties.}, }
@article {pmid26109619, year = {2015}, author = {Sanches, BF and Morgado, J and Carvalho, N and Anjos, R}, title = {Multiple parasitic infections in a cardiac transplant recipient.}, journal = {BMJ case reports}, volume = {2015}, number = {}, pages = {}, pmid = {26109619}, issn = {1757-790X}, mesh = {Abdominal Pain/*parasitology ; Adolescent ; Albendazole/administration &amp; dosage ; Animals ; Anthelmintics/administration &amp; dosage ; Diarrhea/complications/*parasitology ; Feces/parasitology ; Female ; *Heart Transplantation ; Humans ; Ivermectin/administration &amp; dosage ; Praziquantel/administration &amp; dosage ; Schistosoma/*isolation &amp; purification ; Schistosomiasis/complications/*diagnosis/drug therapy ; Strongyloides stercoralis/*isolation &amp; purification ; Strongyloidiasis/complications/*diagnosis/drug therapy ; *Transplant Recipients ; Treatment Outcome ; Vomiting/parasitology ; }, abstract = {Infectious complications represent an important cause of morbidity and death in patients with transplant. Parasitic infections are less frequent than viral and bacterial agents, and are often overlooked. We describe the case of a 13-year-old adolescent, born in São Tomé Island, who was under immunosuppressive therapy after a cardiac transplant. The patient had an intermittent course of diarrhoea, abdominal pain and vomiting. She was admitted dehydrated, and Strongyloides stercoralis, Schistosoma intercalatum and Cystoisospora belli were isolated in her stools. The patient was treated with ivermectin, albendazole, praziquantel and ciprofloxacin with clinical and microbiological resolution. Her immunosuppressive therapy was reduced during hospitalisation. We believe that the parasitic infection was a result of a recrudescence of dormant infections acquired in her homeland. To the best of our knowledge, there are no reports of cystoisosporiasis or schistosomiasis in heart transplant recipients.}, }
@article {pmid26107390, year = {2015}, author = {Habtezion, A}, title = {Inflammation in acute and chronic pancreatitis.}, journal = {Current opinion in gastroenterology}, volume = {31}, number = {5}, pages = {395-399}, pmid = {26107390}, issn = {1531-7056}, support = {R01 DK092421/DK/NIDDK NIH HHS/United States ; R01 DK105263/DK/NIDDK NIH HHS/United States ; DK092421/DK/NIDDK NIH HHS/United States ; }, mesh = {Acute Disease ; Animals ; Disease Models, Animal ; Disease Progression ; Fecal Microbiota Transplantation/trends ; Humans ; Inflammation/*immunology/metabolism/physiopathology/therapy ; Pancreas/*immunology/physiopathology ; Pancreatitis/*immunology/metabolism/physiopathology/therapy ; Pathogen-Associated Molecular Pattern Molecules/*metabolism ; Risk Assessment ; Sensitivity and Specificity ; Signal Transduction ; Toll-Like Receptors/*metabolism ; }, abstract = {PURPOSE OF REVIEW: This report reviews recent animal model and human studies associated with inflammatory responses in acute and chronic pancreatitis.<br><br>RECENT FINDINGS: Animal model and limited human acute and chronic pancreatitis studies unravel the dynamic nature of the inflammatory processes and the ability of the immune cells to sense danger and environmental signals. In acute pancreatitis, such molecules include pathogen-associated molecular pattern recognition receptors such as toll-like receptors, and the more recently appreciated damage-associated molecular pattern molecules or 'alarmin' high mobility group box 1 and IL-33. In chronic pancreatitis, a recent understanding of a critical role for macrophage-pancreatic stellate cell interaction offers a potential targetable pathway that can alter fibrogenesis. Microbiome research in pancreatitis is a new field gaining interest but will require further investigation.<br><br>SUMMARY: Immune cell contribution to the pathogenesis of acute and chronic pancreatitis is gaining more appreciation and further understanding in immune signaling presents potential therapeutic targets that can alter disease progression.}, }
@article {pmid26102296, year = {2015}, author = {Chang, CJ and Lin, CS and Lu, CC and Martel, J and Ko, YF and Ojcius, DM and Tseng, SF and Wu, TR and Chen, YY and Young, JD and Lai, HC}, title = {Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {7489}, pmid = {26102296}, issn = {2041-1723}, mesh = {Animals ; Bacteroides/drug effects ; Body Weight/drug effects ; Diet, High-Fat ; Drugs, Chinese Herbal/*pharmacology ; Dysbiosis/metabolism/microbiology ; Endotoxemia ; Fecal Microbiota Transplantation ; Firmicutes/drug effects ; Fungal Polysaccharides/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Inflammation/metabolism/microbiology ; *Insulin Resistance ; Intestinal Mucosa/metabolism ; Intestines/drug effects ; Mice ; Obesity/metabolism/*microbiology ; Permeability/drug effects ; Plant Extracts/pharmacology ; Proteobacteria/drug effects ; *Reishi ; }, abstract = {Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis-as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels-but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further show that high molecular weight polysaccharides (>300 kDa) isolated from the WEGL extract produce similar anti-obesity and microbiota-modulating effects. Our results indicate that G. lucidum and its high molecular weight polysaccharides may be used as prebiotic agents to prevent gut dysbiosis and obesity-related metabolic disorders in obese individuals.}, }
@article {pmid26098218, year = {2015}, author = {Shen, TC and Albenberg, L and Bittinger, K and Chehoud, C and Chen, YY and Judge, CA and Chau, L and Ni, J and Sheng, M and Lin, A and Wilkins, BJ and Buza, EL and Lewis, JD and Daikhin, Y and Nissim, I and Yudkoff, M and Bushman, FD and Wu, GD}, title = {Engineering the gut microbiota to treat hyperammonemia.}, journal = {The Journal of clinical investigation}, volume = {125}, number = {7}, pages = {2841-2850}, pmid = {26098218}, issn = {1558-8238}, support = {R01 DK089472/DK/NIDDK NIH HHS/United States ; UH2 DK083981/DK/NIDDK NIH HHS/United States ; UH3 DK083981/DK/NIDDK NIH HHS/United States ; HD26979/HD/NICHD NIH HHS/United States ; P30 HD026979/HD/NICHD NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; R01-DK089472/DK/NIDDK NIH HHS/United States ; P30 CA016520/CA/NCI NIH HHS/United States ; UH2/3-DK083981/DK/NIDDK NIH HHS/United States ; T32 DK007066/DK/NIDDK NIH HHS/United States ; P30DK050306/DK/NIDDK NIH HHS/United States ; }, mesh = {Ammonia/metabolism ; Animals ; Bacteria/enzymology/genetics ; Bacterial Proteins/genetics/metabolism ; Bioengineering ; Biological Therapy/*methods ; Chemical and Drug Induced Liver Injury/therapy ; Digestive System/metabolism/*microbiology ; Disease Models, Animal ; Feces/microbiology ; Female ; Genes, Bacterial ; Hyperammonemia/metabolism/*microbiology/*therapy ; Male ; Mice ; Mice, Inbred C57BL ; Mice, SCID ; *Microbiota/physiology ; Time Factors ; Urease/genetics/metabolism ; }, abstract = {Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gut microbiota to reduce urease activity. Animals were depleted of their preexisting gut microbiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility.}, }
@article {pmid26096558, year = {2015}, author = {Witjes, JJ and van Raalte, DH and Nieuwdorp, M}, title = {About the gut microbiome as a pharmacological target in atherosclerosis.}, journal = {European journal of pharmacology}, volume = {763}, number = {Pt A}, pages = {75-78}, doi = {10.1016/j.ejphar.2015.06.023}, pmid = {26096558}, issn = {1879-0712}, mesh = {Animals ; Atherosclerosis/complications/*drug therapy/metabolism/*microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; }, abstract = {The contribution of intestinal bacterial strains (gut microbiota) in the development of cardiometabolic disease is increasingly recognized as potential diagnostic and pharmacological target. Changes in the intestinal bacterial composition and subsequent altered diversity has been associated with presence of chronic low-grade inflammation of mesenteric visceral adipose tissue, a known feature of malign obesity which can eventually lead to insulin resistance and type 2 diabetes mellitus. However, causality still needs to be proven. In this regard, both fecal transplantation studies as well as multiethnic prospective cohorts can help to identify the causally involved driving intestinal bacterial strains in human cardiometabolism. Ultimately, it is expected that novel diagnostic markers as well as therapeutics (pharmabiotics and vaccine strategies) can be developed.}, }
@article {pmid26096320, year = {2015}, author = {Fischer, M and Sipe, BW and Rogers, NA and Cook, GK and Robb, BW and Vuppalanchi, R and Rex, DK}, title = {Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection: description of a protocol with high success rate.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {42}, number = {4}, pages = {470-476}, doi = {10.1111/apt.13290}, pmid = {26096320}, issn = {1365-2036}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*drug therapy ; Colectomy ; Colonoscopy/methods ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Retrospective Studies ; Sepsis/epidemiology ; Shock, Septic/epidemiology ; Vancomycin/*therapeutic use ; }, abstract = {BACKGROUND: Severe and severe/complicated Clostridium difficile infection (CDI) can result in ICU admission, sepsis, toxic megacolon and death. In this setting, colectomy is the standard of care but it is associated with a 50% mortality.<br><br>AIM: To evaluate safety and efficacy of a sequential faecal microbiota transplantation (FMT) and antibiotic protocol in severe and severe/complicated CDI patients who are at high risk for colectomy.<br><br>METHODS: All patients with severe and severe/complicated CDI refractory to oral vancomycin &#xb1; rectal vancomycin and intravenous metronidazole therapy were offered FMT. Treatment consisted of sequential FMTs via colonoscopy with the need for repeat FMT and continued vancomycin guided by clinical response and pseudomembranes at colonoscopy.<br><br>RESULTS: A total of 29 patients underwent FMT between July 2013 and August 2014. The overall treatment response of endoscopic sequential FMT was 93% (27/29), with 100% (10/10) for severe CDI and 89% (17/19) for severe/complicated CDI. A single FMT was performed in 62%, two FMTs were performed in 31% and three FMTs in 7% of patients. The use of non-CDI antibiotics predicted repeat FMT (odds ratio = 17.5). The 30-day all-cause mortality after FMT was 7%, and the cumulative 3-month survival was 76%. Of the two patients who died within 30 days, one underwent colectomy and succumbed to sepsis; the other died from septic shock related to CDI.<br><br>CONCLUSION: The success of a treatment protocol for severe and severe/complicated involving faecal microbiota transplantation and continued vancomycin in selected patients was high, and it warrants further evaluation.}, }
@article {pmid26092095, year = {2015}, author = {Million, M and Hocquart, M and Seghboyan, JM and Griffiths, K and Halfon, P and Lagier, JC and Brouqui, P and Raoult, D}, title = {Faecal microbiota transplantation as salvage therapy for fulminant Clostridium difficile infections.}, journal = {International journal of antimicrobial agents}, volume = {46}, number = {2}, pages = {227-228}, doi = {10.1016/j.ijantimicag.2015.05.002}, pmid = {26092095}, issn = {1872-7913}, mesh = {Aged ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Radiography, Abdominal ; Salvage Therapy/*methods ; Tomography, X-Ray Computed ; Treatment Outcome ; }, }
@article {pmid26080819, year = {2015}, author = {Ren, R and Sun, G and Yang, Y and Peng, L and Zhang, X and Wang, S and Dou, Y and Zhang, X and Wang, Z and Bo, X and Liu, Q and Li, W and Fan, N and Ma, X}, title = {[A pilot study of treating ulcerative colitis with fecal microbiota transplantation].}, journal = {Zhonghua nei ke za zhi}, volume = {54}, number = {5}, pages = {411-415}, pmid = {26080819}, issn = {0578-1426}, mesh = {Anti-Bacterial Agents ; Biological Therapy/adverse effects ; Colitis, Ulcerative/microbiology/*therapy ; Diarrhea/etiology ; Feces/*microbiology ; Female ; Humans ; Intestines/microbiology ; Male ; *Microbiota ; Pilot Projects ; Transplantation/*methods ; Treatment Outcome ; }, abstract = {OBJECTIVE: To explore the procedure, effectiveness and safety of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC).<br><br>METHODS: Seven patients (6 men and 1 woman, aged 17-66 years) with active UC were treated with FMT through endoscopic duodenal infusion or combined endoscopic duodenal and colonic approaches. The clinical manifestations and laboratory results were recorded before and after FMT respectively. Disease response was evaluated with Mayo scores. Fresh fecal suspension prepared from healthy donors who were strictly screened, was infused into patients' intestinal tracts within 6 hours.<br><br>RESULTS: The average disease duration of 7 patients with UC was (9.1 &#xb1; 8.5) years (range 0.5-24.0 years). One patient underwent FMT for three times and one for twice, while the other five were treated for once. The follow-up time was (98.6 &#xb1; 70.8) days (30-210 days). All patients achieved some extent of improvements with the reduction of Mayo scores 7, 4, 6, 5, 6, 9 and 9, respectively. Transient fever, diarrhea and abdominal distension were observed in some patients after FMT, while alleviated spontaneously 2-3 days after the procedure. One patient had high fever and mild ascites caused by secondary infections, which were controlled by the symptomatic treatment and antibiotics. Severe adverse reactions were not found.<br><br>CONCLUSIONS: FMT is effective to active UC, the short-term side effects and complications are basically acceptable and controllable. The long-term efficacy and risks of FMT need to be verified further.}, }
@article {pmid26078735, year = {2015}, author = {Bilal, M and Khehra, R and Strahotin, C and Mitre, R}, title = {Long-Term Follow-Up of Fecal Microbiota Transplantation for Treatment of Recurrent Clostridium difficile Infection in a Dual Solid Organ Transplant Recipient.}, journal = {Case reports in gastroenterology}, volume = {9}, number = {2}, pages = {156-159}, pmid = {26078735}, issn = {1662-0631}, abstract = {Clostridium difficile infection is one of the most frequent causes of healthcare-associated infections, and its rates are also increasing in the community. Mounting evidence suggests that fecal microbiota transplantation (FMT) may be effective; however, as there is paucity of data regarding the use of FMT in patients with solid organ transplants, we present a case of successful FMT in a patient with dual solid organ transplant.}, }
@article {pmid26078557, year = {2015}, author = {Fujimori, S}, title = {What are the effects of proton pump inhibitors on the small intestine?.}, journal = {World journal of gastroenterology}, volume = {21}, number = {22}, pages = {6817-6819}, pmid = {26078557}, issn = {2219-2840}, mesh = {Animals ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Drug Interactions ; Dysbiosis ; Humans ; Intestine, Small/*drug effects/metabolism/microbiology/pathology ; Proton Pump Inhibitors/*adverse effects ; Risk Factors ; }, abstract = {Generally, proton-pump inhibitors (PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury. Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth (SIBO) compared to patients who lack the aforementioned conditions. Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, non-alcoholic fatty liver disease, and autoimmune diseases. When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.}, }
@article {pmid26070003, year = {2015}, author = {Paramsothy, S and Borody, TJ and Lin, E and Finlayson, S and Walsh, AJ and Samuel, D and van den Bogaerde, J and Leong, RW and Connor, S and Ng, W and Mitchell, HM and Kaakoush, N and Kamm, MA}, title = {Donor Recruitment for Fecal Microbiota Transplantation.}, journal = {Inflammatory bowel diseases}, volume = {21}, number = {7}, pages = {1600-1606}, doi = {10.1097/MIB.0000000000000405}, pmid = {26070003}, issn = {1536-4844}, mesh = {Adolescent ; Adult ; Aged ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Male ; Microbiota ; Middle Aged ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Increasing demand for fecal microbiota transplantation (FMT) has created a need for stool banks sourced from long-term healthy donors. Here, we describe our experience in recruiting and screening fecal donors.<br><br>METHODS: Mailbox, newspaper, and online advertisements were used. Potential donors were required to satisfy a prescreen telephone conversation, pass blood and stool investigations, then undertake a screening interview including medical history, physical examination, and evaluation of donor selection criteria.<br><br>RESULTS: One hundred sixteen potential donors were prescreened of whom 74 failed-47 declined based on study donation requirements (primarily related to frequency and duration of donations), 13 had medical comorbidities, 6 variant Creutzfeldt-Jakob disease risk factors, 8 for other reasons. Thirty-eight completed stool and blood testing-1 failed blood testing (indeterminate hepatitis C serology), whereas 15 failed stool investigations (5 Dientamoeba fragilis, 5 Blastocystis hominis, 1 B. hominis and D. fragilis, 1 Giardia intestinalis plus D. fragilis, 1 Norovirus plus Clostridium difficile toxin positive, and 2 leucocytes or erythrocytes on stool microscopy). Of the 18 potential donors proceeding to screening interview, 6 were excluded (3 body mass index >30, 1 illicit drug use, 1 uncontrolled anxiety and concerns regarding compliance, 1 irregular bowel movements after new medication commencement). In total, only 12 of 116 (10%) potential donors were enrolled as study donors.<br><br>CONCLUSIONS: Recruitment of fecal donors for FMT is challenging with only a small percentage ultimately serving as donors. Many were unable or unwilling to meet the donor commitment requirements. A surprisingly large proportion of healthy asymptomatic donors failed stool testing, primarily due to gastrointestinal parasites.}, }
@article {pmid26070001, year = {2015}, author = {Perry, T and Jovel, J and Patterson, J and Wong, G and Fedorak, RN and Thiesen, A and Dicken, B and Madsen, KL}, title = {Fecal Microbial Transplant After Ileocolic Resection Reduces Ileitis but Restores Colitis in IL-10-/- Mice.}, journal = {Inflammatory bowel diseases}, volume = {21}, number = {7}, pages = {1479-1490}, doi = {10.1097/MIB.0000000000000383}, pmid = {26070001}, issn = {1536-4844}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Anastomosis, Surgical/*methods ; Animals ; *Bacterial Translocation ; Colectomy ; Colitis/genetics/microbiology/*therapy ; Colon/*surgery ; Disease Models, Animal ; Dysbiosis ; Feces/microbiology ; Ileitis/genetics/microbiology/*therapy ; Ileum/*surgery ; In Situ Hybridization, Fluorescence ; Interleukin-10/deficiency/*genetics ; Male ; Mice ; RNA/genetics ; }, abstract = {BACKGROUND: Ileocolic resection (ICR) is frequently performed for Crohn's disease; however, disease commonly recurs early in the neoterminal ileum. The aim of this study was to use the IL-10(-/-) mouse to determine the effects of ICR on gut microbiome and immune function and if postoperative fecal microbial transplant (FMT) would improve disease.<br><br>METHODS: ICR was performed in 129S1/SvlmJ IL10(-/-) mice followed by FMT using stool from wild-type mice. Sham-transplant mice received their own stool. Stool samples were collected on day 0, day 13 (after ICR), and day 27 (after FMT) for whole metagenome shot-gun sequencing. Mucosal-associated bacteria were quantified with quantitative PCR and visualized by fluorescent in situ hybridization. Tissue cytokines were measured with multiplex arrays and mononuclear phagocyte populations by flow cytometry.<br><br>RESULTS: Surgery induced microbial functional and taxonomic shifts, decreased diversity, and depleted Bacteroidia and Clostridia. ICR mice had reduced colitis but worse ileitis with bacterial overgrowth, increased translocation, and reduction in tissue macrophages. FMT prevented ileitis but restored colitis and allowed for a bloom of &#x3b3;-proteobacteria. In the colon, ICR and sham transplant were associated with recruitment of tolerogenic dendritic cells, whereas FMT shifted these immune cell subsets to control profiles along with increasing cytokine levels.<br><br>CONCLUSIONS: This study suggests that surgical-induced immune dysfunction and microbial dysbiosis with impaired clearance may be the underlying cause of the early ulcerations found in the ileum of patients with Crohn's disease after ICR. FMT has an immunostimulatory effect on the postoperative intestine, which was beneficial in preventing ileitis, but detrimental in restoring colonic injury after surgery.}, }
@article {pmid26066984, year = {2015}, author = {de Noya, BA and González, ON}, title = {An ecological overview on the factors that drives to Trypanosoma cruzi oral transmission.}, journal = {Acta tropica}, volume = {151}, number = {}, pages = {94-102}, doi = {10.1016/j.actatropica.2015.06.004}, pmid = {26066984}, issn = {1873-6254}, mesh = {Animals ; Animals, Domestic/parasitology ; Animals, Wild/parasitology ; Chagas Disease/epidemiology/parasitology/*transmission ; Disease Outbreaks ; *Ecology ; Feces/parasitology ; Female ; *Food Contamination ; Fruit and Vegetable Juices/*parasitology ; Humans ; Male ; South America/epidemiology ; Triatoma/*parasitology ; Trypanosoma cruzi/*parasitology ; Zoonoses/*parasitology ; }, abstract = {American trypanosomiasis is one of the few native parasites of this continent. As a zoonosis, Trypanosoma cruzi infects about 180 species out of 25 families of mammals. Its regular transmission is through triatomines, which can easily transmit parasites either by the skin route (contamination of mammals skin with their feces) or by oral route (ingestion of food contaminated with complete triatomines or their feces) and additionally through haematogenous via (congenital and transfusional) and by tissues (transplants). The oral route, which seems to be the ancestral form of transmission to wild and domestic mammals, has recently become more important after the success achieved in the control of domicile vectors using residual pesticides. From its initial diagnosis in 1967, tens of oral outbreaks have been diagnosed mostly in the Brazilian Amazon and subsequently in other four countries in South America. Environmental imbalance caused by man through the invasion and deforestation of woodlands, results in reduction of biodiversity of mammals as food source for triatomines, affecting the "dilution effect" of T. cruzi in the nature increasing the risk of human infection. On the other hand, triatomines invade houses looking for new blood sources. One of the consequences of domiciliated triatomines is the food contamination spread, especially in home-made juices, which has been the source of infection of most oral outbreaks. Other biotic and abiotic factors help to explain the recent increase of oral transmission outbreaks of Chagas disease, distributed in nine eco-regions of America.}, }
@article {pmid26065325, year = {2015}, author = {Vindigni, SM and Surawicz, CM}, title = {The gut microbiome: a clinically significant player in transplantation?.}, journal = {Expert review of clinical immunology}, volume = {11}, number = {7}, pages = {781-783}, doi = {10.1586/1744666X.2015.1043894}, pmid = {26065325}, issn = {1744-8409}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Dysbiosis/*microbiology ; Graft Rejection/*microbiology ; Humans ; Intestines/*microbiology ; *Microbiota ; *Organ Transplantation ; Portraits as Topic ; }, abstract = {The intestinal microbiome is critical to digestion, metabolism and protection from pathogenic organisms. Dysbiosis, or alteration of this microbiome, can result in Clostridium difficile infection and may play a role in other conditions. Patients undergoing solid organ transplantation (e.g., kidney, lung, liver, small bowel) and hematopoietic stem cell transplantation have a shift in the gut microbiome with a decrease in predominant organisms, a loss of bacterial diversity and emergence of a new dominant population. This translates into increased morbidity and mortality with risk of infection and rejection. We discuss the changes seen in the microbiome and its possible consequences. It may be important to develop strategies to restore the normal microbiome in such patients.}, }
@article {pmid26063385, year = {2015}, author = {Borgia, G and Maraolo, AE and Foggia, M and Buonomo, AR and Gentile, I}, title = {Fecal microbiota transplantation for Clostridium difficile infection: back to the future.}, journal = {Expert opinion on biological therapy}, volume = {15}, number = {7}, pages = {1001-1014}, doi = {10.1517/14712598.2015.1045872}, pmid = {26063385}, issn = {1744-7682}, mesh = {Clinical Trials as Topic ; Clostridioides difficile/isolation &amp; purification/physiology ; Clostridium Infections/microbiology/physiopathology/*therapy ; Evidence-Based Practice ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Recurrence ; }, abstract = {INTRODUCTION: Clostridium difficile infection (CDI) is a leading cause of diarrhea in the industrialized world. The estimated costs of this infection are impressive: over 3.2 billion dollars annually in the US. The introduction of fecal microbiota transplantation (FMT) to clinical practice can be considered a Copernican Revolution. The rationale of this approach consists of correcting the imbalance of the organisms dwelling in the gut by reintroducing a normal flora.<br><br>AREAS COVERED: This review focuses on the indication for FMT in CDI; it examines in-depth the most relevant aspects of the techniques used, and the safety and efficacy of this new 'old' therapy.<br><br>EXPERT OPINION: Authoritative guidelines about the management of CDI strongly recommend FMT for multiple recurrent episodes of infection by C. difficile unresponsive to repeated antibiotic treatment. The cure rates are about 90%, with no serious adverse events having been reported. The main concerns are the long-term outcomes, lack of a standardized procedure for the delivery of donor material, and a cultural barrier to the transplantation of fecal microbiota. A promising solution to some of these problems could be the use of a more acceptable administration route of fecal material, namely, oral capsules.}, }
@article {pmid26046241, year = {2015}, author = {Petra, AI and Panagiotidou, S and Hatziagelaki, E and Stewart, JM and Conti, P and Theoharides, TC}, title = {Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation.}, journal = {Clinical therapeutics}, volume = {37}, number = {5}, pages = {984-995}, pmid = {26046241}, issn = {1879-114X}, support = {R01 AR047652/AR/NIAMS NIH HHS/United States ; R01 NS038326/NS/NINDS NIH HHS/United States ; AR47652/AR/NIAMS NIH HHS/United States ; NS38326/NS/NINDS NIH HHS/United States ; }, mesh = {Anxiety/immunology/microbiology ; Attention Deficit Disorder with Hyperactivity/immunology/microbiology ; Brain/*physiopathology ; Cytokines/immunology ; Depression/immunology/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Hypothalamo-Hypophyseal System/physiopathology ; Multiple Sclerosis/immunology/microbiology ; Nervous System Diseases/immunology/*microbiology ; Neuroimmunomodulation/physiology ; Pituitary-Adrenal System/physiopathology ; }, abstract = {PURPOSE: Gut microbiota regulate intestinal function and health. However, mounting evidence indicates that they can also influence the immune and nervous systems and vice versa. This article reviews the bidirectional relationship between the gut microbiota and the brain, termed the microbiota-gut-brain (MGB) axis, and discusses how it contributes to the pathogenesis of certain disorders that may involve brain inflammation.<br><br>METHODS: Articles were identified with a search of Medline (starting in 1980) by using the key words anxiety, attention-deficit hypersensitivity disorder (ADHD), autism, cytokines, depression, gut, hypothalamic-pituitary-adrenal (HPA) axis, inflammation, immune system, microbiota, nervous system, neurologic, neurotransmitters, neuroimmune conditions, psychiatric, and stress.<br><br>FINDINGS: Various afferent or efferent pathways are involved in the MGB axis. Antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and essential metabolites all convey information to the central nervous system about the intestinal state. Conversely, the hypothalamic-pituitary-adrenal axis, the central nervous system regulatory areas of satiety, and neuropeptides released from sensory nerve fibers affect the gut microbiota composition directly or through nutrient availability. Such interactions seem to influence the pathogenesis of a number of disorders in which inflammation is implicated, such as mood disorder, autism-spectrum disorders, attention-deficit hypersensitivity disorder, multiple sclerosis, and obesity.<br><br>IMPLICATIONS: Recognition of the relationship between the MGB axis and the neuroimmune systems provides a novel approach for better understanding and management of these disorders. Appropriate preventive measures early in life or corrective measures such as use of psychobiotics, fecal microbiota transplantation, and flavonoids are discussed.}, }
@article {pmid26040234, year = {2015}, author = {He, B and Nohara, K and Ajami, NJ and Michalek, RD and Tian, X and Wong, M and Losee-Olson, SH and Petrosino, JF and Yoo, SH and Shimomura, K and Chen, Z}, title = {Transmissible microbial and metabolomic remodeling by soluble dietary fiber improves metabolic homeostasis.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {10604}, pmid = {26040234}, issn = {2045-2322}, support = {R01 GM114424/GM/NIGMS NIH HHS/United States ; 2P30-DK056338/DK/NIDDK NIH HHS/United States ; R01 AG045828/AG/NIA NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01, AG045828/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Biomarkers ; Blood Glucose ; Cluster Analysis ; *Dietary Fiber ; Disease Models, Animal ; *Gastrointestinal Microbiome ; *Homeostasis ; Metabolic Diseases/metabolism/microbiology ; *Metabolome ; *Metabolomics ; Mice ; Polysaccharides/metabolism ; }, abstract = {Dietary fibers are increasingly appreciated as beneficial nutritional components. However, a requisite role of gut microbiota in fiber function and the overall impact of fibers on metabolomic flux remain unclear. We herein showed enhancing effects of a soluble resistant maltodextrin (RM) on glucose homeostasis in mouse metabolic disease models. Remarkably, fecal microbiota transplantation (FMT) caused pronounced and time-dependent improvement in glucose tolerance in RM recipient mice, indicating a causal relationship between microbial remodeling and metabolic efficacy. Microbial 16S sequencing revealed transmissible taxonomic changes correlated with improved metabolism, notably enrichment of probiotics and reduction of Alistipes and Bacteroides known to associate with high fat/protein diets. Metabolomic profiling further illustrated broad changes, including enrichment of phenylpropionates and decreases in key intermediates of glucose utilization, cholesterol biosynthesis and amino acid fermentation. These studies elucidate beneficial roles of RM-dependent microbial remodeling in metabolic homeostasis, and showcase prevalent health-promoting potentials of dietary fibers.}, }
@article {pmid26036516, year = {2015}, author = {Pontes, AM and Borborema, J and Correia, CR and de Almeida, WL and Maciel, RF}, title = {A rare paracoccidioidomycosis diagnosis in a kidney transplant receptor: case report.}, journal = {Transplantation proceedings}, volume = {47}, number = {4}, pages = {1048-1050}, doi = {10.1016/j.transproceed.2015.03.006}, pmid = {26036516}, issn = {1873-2623}, mesh = {Biopsy ; Diagnosis, Differential ; Humans ; Kidney/microbiology/*pathology ; *Kidney Transplantation ; Male ; Middle Aged ; Paracoccidioidomycosis/*diagnosis ; Tomography, X-Ray Computed ; *Transplant Recipients ; }, abstract = {INTRODUCTION: Paracoccidioidomycosis (PCM) is a systemic mycosis of chronic presentation more frequent in adults, which may lead to disseminated severe and lethal forms involving the lungs, skin, lymph nodes, spleen, liver, and lymphoid organs of the digestive tract. Common in Latin America, it is rare in transplanted patients, with few cases described in the literature.<br><br>PURPOSE: To report a case of a patient who underwent kidney transplant 3 years ago with a pseudotumoral cervical PCM diagnosis.<br><br>METHODS: A male patient, 45 years old, who underwent kidney transplantation 3 years ago presenting with diarrhea, severe weight loss, and anemia; no breathing complaints. Parasitological stool tests, fecal culture, urine culture, and abdomen USG were performed in order to assess the diarrhea, and were inconclusive. He was treated with antibiotics and antiparasitic drugs with no improvement and continued with weight loss of 15 kg within 3 months. Immunosuppression was changed, with the mycophenolic acid reduced until it was replaced by everolimus. The diarrhea returned to intensify, and there was an increase in the creatinine (from 1.5 to 3.4). He was empirically treated with sulfamethoxazole/trimethoprim, with total remission of the diarrhea. The patient underwent a kidney biopsy, anti-HIV examinations, PCR BK virus, and PCR for Mycobacterium tuberculosis-with no diagnostic conclusion. During his fifth hospitalization (6 months after the beginning of the diagnostic research), presenting a quite compromised general state, loss of 20 kg, anemia, kidney failure, and fever, he developed skin lesions on the legs and a voluminous and hard tumor in the right cervical region. Chest computed tomography was performed, and the tumoral lesions were removed from those regions. He was started on tuberculostatics and underwent a biopsy of the cervical tumoral lesion.<br><br>RESULT: Biopsy of the cervical tumor showed a fungal infection by paracoccidioidomycosis. The BAAR test of the biopsy was negative. The patient died a few weeks after the diagnosis.<br><br>CONCLUSION: The association between the organ transplant and PCM is rare and, in unusual clinical presentations, the diagnosis difficulty may compromise a successful treatment.}, }
@article {pmid26035536, year = {2015}, author = {Benno, P and Befrits, R and Berstad, A and Dahlgren, AL and Norin, E and Midtvedt, T}, title = {[Underlying dysbiosis may be the cause of some forms of IBS. Patients were free of symptoms after the administration of microbiota].}, journal = {Lakartidningen}, volume = {112}, number = {}, pages = {}, pmid = {26035536}, issn = {1652-7518}, mesh = {Adult ; Biological Therapy/methods ; Dysbiosis/*complications ; Feces/microbiology ; Female ; Humans ; Irritable Bowel Syndrome/*microbiology ; Male ; Microbiota ; Transplantation/methods ; }, abstract = {Two cases of post-infectious IBS were successfully treated with transplantation of an anaerobic cultivated human intestinal microbiota. This suggests that a dysbiosis of the intestinal microbiota could be the culprit at least in some cases of IBS. Resetting the gut microbiota might be a possible solution for these patients that otherwise may face a life-long reduction in quality of life. Studies have suggested that conditions as varied as chronic constipation, metabolic syndrome, autoimmunity, asthma, cardiovascular disease and Crohn's disease may be caused by intestinal dysbiosis. If this is the case we would like to suggest a new term: Dysbiotic Bowel Syndrome (DBS).}, }
@article {pmid26034756, year = {2015}, author = {Weil, AA and Hohmann, EL}, title = {Fecal microbiota transplant: benefits and risks.}, journal = {Open forum infectious diseases}, volume = {2}, number = {1}, pages = {ofv005}, pmid = {26034756}, issn = {2328-8957}, support = {T32 AI007061/AI/NIAID NIH HHS/United States ; }, }
@article {pmid26034755, year = {2015}, author = {Alang, N and Kelly, CR}, title = {Weight gain after fecal microbiota transplantation.}, journal = {Open forum infectious diseases}, volume = {2}, number = {1}, pages = {ofv004}, pmid = {26034755}, issn = {2328-8957}, abstract = {Fecal microbiota transplantation (FMT) is a promising treatment for recurrent Clostridium difficile infection. We report a case of a woman successfully treated with FMT who developed new-onset obesity after receiving stool from a healthy but overweight donor. This case may stimulate further studies on the mechanisms of the nutritional-neural-microbiota axis and reports of outcomes in patients who have used nonideal donors for FMT.}, }
@article {pmid26031684, year = {2015}, author = {Norén, T}, title = {Feces transplantation - EU recommendations.}, journal = {Microbial ecology in health and disease}, volume = {26}, number = {}, pages = {28068}, pmid = {26031684}, issn = {0891-060X}, }
@article {pmid26031677, year = {2015}, author = {Bakken, JS}, title = {Feces transplantation for recurrent Clostridium difficile infection: US experience and recommendations.}, journal = {Microbial ecology in health and disease}, volume = {26}, number = {}, pages = {27657}, pmid = {26031677}, issn = {0891-060X}, }
@article {pmid26025991, year = {2015}, author = {Goldberg, EJ and Bhalodia, S and Jacob, S and Patel, H and Trinh, KV and Varghese, B and Yang, J and Young, SR and Raffa, RB}, title = {Clostridium difficile infection: A brief update on emerging therapies.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {72}, number = {12}, pages = {1007-1012}, doi = {10.2146/ajhp140645}, pmid = {26025991}, issn = {1535-2900}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/methods ; Humans ; Probiotics/therapeutic use ; Vaccines/administration &amp; dosage ; }, abstract = {PURPOSE: Established and investigational antibiotic, monoclonal antibody, vaccine, and microbe-based approaches to the prevention and treatment of Clostridium difficile infection (CDI) are reviewed.<br><br>SUMMARY: CDI is increasingly prevalent in the United States and other countries, particularly among hospitalized patients and the elderly, who are at high risk for potentially fatal CDI-related enterotoxic diarrhea. Established therapies for CDI such as vancomycin and metronidazole (an off-label use) are limited by poor efficacy and high recurrence rates. An investigational antibiotic with potent in vitro activity against all C. difficile strains (including the hypervirulent BI/NAP1/027 strain) has yielded encouraging results in early clinical trials. Another promising approach involves the use of monoclonal antibodies with selective activity against toxins responsible for CDI-associated diarrhea; in a small Phase II clinical trial, a single monoclonal antibody infusion in combination with vancomycin or metronidazole therapy was more effective than antibiotic therapy alone in preventing CDI relapse. Other emerging approaches to CDI treatment and prophylaxis include the use of vaccines against C. difficile toxins (several C. difficile-targeted vaccines are under development in Europe and the United States); microbe-based strategies such as fecal microbiota transplants, "microbial ecosystem therapeutics," and probiotic supplements; and an investigational encapsulated form of &#x3b2;-lactamase designed to prevent C. difficile colonization from progressing to CDI.<br><br>CONCLUSION: The current antibiotic therapies for CDI, mainly vancomycin and (off-label) metronidazole and the newer agent fidaxomicin, have limitations with respect to efficacy, recurrence rates, and adverse effects, but a variety of promising approaches are emerging.}, }
@article {pmid26021232, year = {2015}, author = {Grinspan, AM and Kelly, CR}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis: Not Just Yet.}, journal = {Gastroenterology}, volume = {149}, number = {1}, pages = {15-18}, doi = {10.1053/j.gastro.2015.05.030}, pmid = {26021232}, issn = {1528-0012}, mesh = {Biological Therapy/*methods ; Colitis, Ulcerative/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; }, }
@article {pmid26002300, year = {2015}, author = {Hage, E and Gerd Liebert, U and Bergs, S and Ganzenmueller, T and Heim, A}, title = {Human mastadenovirus type 70: a novel, multiple recombinant species D mastadenovirus isolated from diarrhoeal faeces of a haematopoietic stem cell transplantation recipient.}, journal = {The Journal of general virology}, volume = {96}, number = {9}, pages = {2734-2742}, doi = {10.1099/vir.0.000196}, pmid = {26002300}, issn = {1465-2099}, mesh = {Adenoviridae Infections/etiology/*virology ; Diarrhea/*virology ; Feces/*virology ; Genome, Viral ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Mastadenovirus/classification/*genetics/*isolation &amp; purification ; Middle Aged ; Molecular Sequence Data ; Phylogeny ; Postoperative Complications/*virology ; *Recombination, Genetic ; Viral Proteins/genetics ; }, abstract = {A human mastadenovirus D (HAdV-D) isolated from diarrhoeal faeces of an allogeneic haematopoietic stem cell transplant (SCT) recipient was found to be non-typable by sequencing of loops 1 and 2 of the hexon main neutralization epitope ('imputed serology'). In contrast to HAdV-C, HAdV-D infections are rarely observed in SCT patients. Therefore, the whole genome of this isolate was sequenced and phylogenetically analysed. In addition, microneutralization testing with type-specific antisera was performed. A complete genomic sequence of 35.2 kb in length with a GC content of 57 % was obtained and found to be distantly related to HAdV-D27 (96.25 % identity). Imputed serology implicated a new type with a nucleotide sequence identity of only 96.11 % to HAdV-D37 (loop 1) and 95.76 % to HAdV-D30 and HAdV-D37 (loop 2). Microneutralization testing confirmed that this clinical isolate was not neutralized by HAdV-D37- or HAdV-D30-specific antisera. The penton base gene showed a novel sequence, which clustered with HAdV-D38, but bootscan analysis indicated an intra-penton recombination event with HAdV-D60. Another recombination event was detected within the early gene region E3 with the 12.2 kDa and CR1-α genes derived from HAdV-D58. Moreover, the E4 region was derived from HAdV-D13, but all these genes had evolved significantly from their ancestors. By contrast, the recombinant fibre gene was almost 100 % identical to HAdV-D29. In conclusion, the genomics of this novel HAdV, designated the HAdV-D70 [P70H70F29] prototype, supported the significance of multiple recombinations in the phylogeny of HAdV-D.}, }
@article {pmid26002031, year = {2015}, author = {Goto, Y and Kurashima, Y and Kiyono, H}, title = {The gut microbiota and inflammatory bowel disease.}, journal = {Current opinion in rheumatology}, volume = {27}, number = {4}, pages = {388-396}, doi = {10.1097/BOR.0000000000000192}, pmid = {26002031}, issn = {1531-6963}, mesh = {Bacteria/immunology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunity, Mucosal/immunology ; Inflammatory Bowel Diseases/*immunology/therapy ; Intestinal Mucosa/immunology/microbiology ; Symbiosis/immunology ; }, abstract = {PURPOSE OF REVIEW: Inflammatory bowel diseases (IBDs) reflect the cooperative influence of numerous host and environmental factors, including those of elements of the intestinal immune system, the gut microbiota, and dietary habits. This review focuses on features of the gut microbiota and mucosal immune system that are important in the development and control of IBDs.<br><br>RECENT FINDINGS: Gut innate-type immune cells, including dendritic cells, innate lymphoid cells, and mast cells, educate acquired-type immune cells and intestinal epithelial cells to achieve a symbiotic relationship with commensal bacteria. However, perturbation of the number or type of commensal microorganisms and endogenous genetic polymorphisms that affect immune responses and epithelial barrier system can ultimately lead to IBDs. Providing beneficial bacteria or fecal microbiota transplants helps to reestablish the intestinal environment, maintain its homeostasis, and ameliorate IBDs.<br><br>SUMMARY: The gut immune system participates in a symbiotic milieu that includes cohabiting commensal bacteria. However, dysbiotic conditions and aberrations in the epithelial barrier and gut immune system can disrupt the mutualistic relationship between the host and gut microbiota, leading to IBDs. Progress in our molecular and cellular understanding of this relationship has yielded numerous insights regarding clinical applications for the treatment of IBDs.}, }
@article {pmid25998053, year = {2015}, author = {Patel, VC and Shawcross, DL}, title = {Salivary microbiota-immune profiling in cirrhosis: could this be the noninvasive strategy that will revolutionize prognostication in hepatology?.}, journal = {Hepatology (Baltimore, Md.)}, volume = {62}, number = {4}, pages = {1001-1003}, doi = {10.1002/hep.27870}, pmid = {25998053}, issn = {1527-3350}, support = {MR/J006742/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Hepatic Encephalopathy/*microbiology ; Humans ; Intestines/*microbiology ; Liver Cirrhosis/*microbiology ; Male ; Saliva/*microbiology ; }, }
@article {pmid25989926, year = {2015}, author = {Rotelli, MT and Di Lena, M and Cavallini, A and Lippolis, C and Bonfrate, L and Chetta, N and Portincasa, P and Altomare, DF}, title = {Fecal microRNA profile in patients with colorectal carcinoma before and after curative surgery.}, journal = {International journal of colorectal disease}, volume = {30}, number = {7}, pages = {891-898}, pmid = {25989926}, issn = {1432-1262}, mesh = {Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Colorectal Neoplasms/*genetics/*surgery ; *Colorectal Surgery ; Demography ; Feces/*chemistry ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Intestinal Mucosa/metabolism/pathology ; Male ; MicroRNAs/*genetics/metabolism ; Middle Aged ; RNA Stability/genetics ; ROC Curve ; Reproducibility of Results ; }, abstract = {PURPOSE: The purpose of this study was to explore the potential role of deranged fecal microRNA (miRNA) pattern as a reliable warning signal of colorectal cancer (CRC), a subset of fecal CRC-related miRNAs was evaluated in CRC patients, before and after surgery, and in healthy controls.<br><br>METHODS: Twenty CRC patients and 20 age/sex-matched healthy volunteers with negative colonoscopy entered the study. Cancer biopsy, colonic mucosa from the resected specimens, and fecal samples from patients and controls were screened for 13 miRNAs involved in CRC onset and progressions by reverse transcription quantitative PCR (RT-qPCR). Postoperative evaluation of fecal miRNAs was carried out after a median follow-up of 18 months (range 12-30).<br><br>RESULTS: Two out 13 miRNAs (RNU6B, miR-16-3p) were used as internal controls leaving 11 available for analysis. Cancer tissue contained significantly higher expression of all miRNAs, compared to normal mucosa (p&#x2009;<&#x2009;0.05). Expression of preoperative levels of five fecal miRNAs, (miR-19-b-3p, miR-20a-5p, miR-21-3p, miR92a-3p, miR141) was significantly higher in CRC patients compared to controls and significantly decreased after curative surgery. Three out of these five miRNAs (miR20a-5p, miR21-3p, and miR141) returned to values comparable to normal controls.<br><br>CONCLUSIONS: A set of three specific fecal miRNAs is overexpressed before surgery, and return within the normal range after cancer removal could be considered as an appealing opportunity for a new reliable tool for CRC secondary prevention. However, their role needs to be explored in large prospective trials and compared with the existing screening tools.}, }
@article {pmid25982290, year = {2015}, author = {Kelly, CR and Kahn, S and Kashyap, P and Laine, L and Rubin, D and Atreja, A and Moore, T and Wu, G}, title = {Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook.}, journal = {Gastroenterology}, volume = {149}, number = {1}, pages = {223-237}, pmid = {25982290}, issn = {1528-0012}, support = {K08 DK100638/DK/NIDDK NIH HHS/United States ; R01 GM103591/GM/NIGMS NIH HHS/United States ; R21 DK093839/DK/NIDDK NIH HHS/United States ; 1R21DK093839-01A1/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Biological Therapy/*methods ; Clostridioides difficile/isolation &amp; purification/*pathogenicity ; Clostridium Infections/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; Middle Aged ; }, abstract = {The community of microorganisms within the human gut (or microbiota) is critical to health and functions with a level of complexity comparable to that of an organ system. Alterations of this ecology (or dysbiosis) have been implicated in a number of disease states, and the prototypical example is Clostridium difficile infection (CDI). Fecal microbiota transplantation (FMT) has been demonstrated to durably alter the gut microbiota of the recipient and has shown efficacy in the treatment of patients with recurrent CDI. There is hope that FMT may eventually prove beneficial for the treatment of other diseases associated with alterations in gut microbiota, such as inflammatory bowel disease, irritable bowel syndrome, and metabolic syndrome, to name a few. Although the basic principles that underlie the mechanisms by which FMT shows therapeutic efficacy in CDI are becoming apparent, further research is needed to understand the possible role of FMT in these other conditions. Although relatively simple to perform, questions regarding both short-term and long-term safety as well as the complex and rapidly evolving regulatory landscape has limited widespread use. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current "whole-stool" transplants to increase safety and tolerability. Encapsulated formulations, full-spectrum stool-based products, and defined microbial consortia are all in the immediate future.}, }
@article {pmid25977230, year = {2015}, author = {Jenq, RR and Taur, Y and Devlin, SM and Ponce, DM and Goldberg, JD and Ahr, KF and Littmann, ER and Ling, L and Gobourne, AC and Miller, LC and Docampo, MD and Peled, JU and Arpaia, N and Cross, JR and Peets, TK and Lumish, MA and Shono, Y and Dudakov, JA and Poeck, H and Hanash, AM and Barker, JN and Perales, MA and Giralt, SA and Pamer, EG and van den Brink, MR}, title = {Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {21}, number = {8}, pages = {1373-1383}, pmid = {25977230}, issn = {1523-6536}, support = {R01 AI101406/AI/NIAID NIH HHS/United States ; R25 CA020449/CA/NCI NIH HHS/United States ; P01-CA023766/CA/NCI NIH HHS/United States ; T32 CA009207/CA/NCI NIH HHS/United States ; R01-AI095706/AI/NIAID NIH HHS/United States ; R01-HL069929/HL/NHLBI NIH HHS/United States ; R01-AI042135/AI/NIAID NIH HHS/United States ; R01 AI100288/AI/NIAID NIH HHS/United States ; P30-CA008748/CA/NCI NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; R01-AI101406/AI/NIAID NIH HHS/United States ; R01-AI080455/AI/NIAID NIH HHS/United States ; HHSN272200900059C/AI/NIAID NIH HHS/United States ; R01 HL069929/HL/NHLBI NIH HHS/United States ; P30 CA072720/CA/NCI NIH HHS/United States ; K23-AI095398/AI/NIAID NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; K23 AI095398/AI/NIAID NIH HHS/United States ; R01 AI080455/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*metabolism ; Cohort Studies ; Female ; Graft vs Host Disease/*mortality ; Humans ; Intestinal Mucosa/metabolism ; Intestines/*microbiology ; Male ; Risk Factors ; Survival Analysis ; }, abstract = {The relationship between intestinal microbiota composition and acute graft-versus-host disease (GVHD) after allogeneic blood/marrow transplantation (allo-BMT) is not well understood. Intestinal bacteria have long been thought to contribute to GVHD pathophysiology, but recent animal studies in nontransplant settings have found that anti-inflammatory effects are mediated by certain subpopulations of intestinal commensals. Hypothesizing that a more nuanced relationship may exist between the intestinal bacteria and GVHD, we evaluated the fecal bacterial composition of 64 patients 12 days after BMT. We found that increased bacterial diversity was associated with reduced GVHD-related mortality. Furthermore, harboring increased amounts of bacteria belonging to the genus Blautia was associated with reduced GVHD lethality in this cohort and was confirmed in another independent cohort of 51 patients from the same institution. Blautia abundance was also associated with improved overall survival. We evaluated the abundance of Blautia with respect to clinical factors and found that loss of Blautia was associated with treatment with antibiotics that inhibit anaerobic bacteria and receiving total parenteral nutrition for longer durations. We conclude that increased abundance of commensal bacteria belonging to the Blautia genus is associated with reduced lethal GVHD and improved overall survival.}, }
@article {pmid25962241, year = {2015}, author = {Maharshak, N}, title = {[Use of fecal microbial transplantations for disease states in Israel].}, journal = {Harefuah}, volume = {154}, number = {3}, pages = {152-4, 213}, pmid = {25962241}, issn = {0017-7768}, mesh = {Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Diabetes Mellitus/microbiology/therapy ; Feces/*microbiology ; Humans ; Inflammatory Bowel Diseases/microbiology/therapy ; Israel ; Obesity/microbiology/therapy ; }, abstract = {The enteric microbial population (microbiota) has a tremendous impact on our health and multiple disease states are associated with an alteration of the enteric microbial profile. It has been suggested that fecal microbial transplantation (FMT)--a transfer of fecal microbiota from a healthy donor to a sick person, may be beneficial for the treatment of certain diseases such as obesity, diabetes and inflammatory bowel diseases. Currently, this treatment has been approved in Israel, as well as in other countries, for the treatment of recurrent Clostridium difficile infection (RCDI). The establishment of a stool bank from healthy donors makes this therapy available and easy to use. The rationale for using FMT for RCDI, and the methods for its performance and for choosing patients and donors, along with the open questions and the future for this therapy, are presented in the current editorial.}, }
@article {pmid25961766, year = {2015}, author = {O'Meara, A and Kapel, N and Xhaard, A and Sicre de Fontbrune, F and Manéné, D and Dhedin, N and de Latour, RP and Socié, G and Robin, M}, title = {Fecal calprotectin and α1-antitrypsin dynamics in gastrointestinal GvHD.}, journal = {Bone marrow transplantation}, volume = {50}, number = {8}, pages = {1105-1109}, pmid = {25961766}, issn = {1476-5365}, mesh = {Biomarkers/metabolism ; *Feces ; Female ; Gastrointestinal Diseases/drug therapy/*metabolism ; Graft vs Host Disease/drug therapy/*metabolism ; Hematologic Neoplasms/metabolism/therapy ; Humans ; Leukocyte L1 Antigen Complex/*metabolism ; Male ; Middle Aged ; Prospective Studies ; alpha 1-Antitrypsin/*metabolism ; }, abstract = {In a previous study, the fecal biomarkers calprotectin and α1-antitrypsin (α1-AT) at symptom onset were reported to be significantly associated with the response to steroids in gastrointestinal GvHD (GI-GvHD). The purpose of this trial was to evaluate the dynamics of the fecal biomarkers calprotectin and α1-AT throughout the course of GvHD. Patients who were refractory to steroids had initially higher biomarker levels and in the course of GvHD demonstrated a continuous increase in fecal biomarkers. In contrast, the dynamics of calprotectin and α1-AT demonstrated low and decreasing levels in cortico-sensitive GvHD. In steroid-refractory patients who received a second line of treatment, the biomarker levels at the beginning of second-line treatment did not predict the subsequent response. Nevertheless, calprotectin levels progressively decreased in subsequent responders, whereas non-responders demonstrated continuously high levels of calprotectin. α1-AT values correlated to a lesser extent with the response to second-line treatment and remained elevated in both non-responders and responders. In conclusion, calprotectin monitoring can be of use in the management of immunosuppressive treatment in GI-GvHD.}, }
@article {pmid25956237, year = {2015}, author = {Frye, RE and Slattery, J and MacFabe, DF and Allen-Vercoe, E and Parker, W and Rodakis, J and Adams, JB and Krajmalnik-Brown, R and Bolte, E and Kahler, S and Jennings, J and James, J and Cerniglia, CE and Midtvedt, T}, title = {Approaches to studying and manipulating the enteric microbiome to improve autism symptoms.}, journal = {Microbial ecology in health and disease}, volume = {26}, number = {}, pages = {26878}, pmid = {25956237}, issn = {0891-060X}, abstract = {There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing number of research studies have provided evidence that the composition of the gut (enteric) microbiome (GM) in at least a subset of individuals with autism spectrum disorder (ASD) deviates from what is usually observed in typically developing individuals. There are several lines of research that suggest that specific changes in the GM could be causative or highly associated with driving core and associated ASD symptoms, pathology, and comorbidities which include gastrointestinal symptoms, although it is also a possibility that these changes, in whole or in part, could be a consequence of underlying pathophysiological features associated with ASD. However, if the GM truly plays a causative role in ASD, then the manipulation of the GM could potentially be leveraged as a therapeutic approach to improve ASD symptoms and/or comorbidities, including gastrointestinal symptoms. One approach to investigating this possibility in greater detail includes a highly controlled clinical trial in which the GM is systematically manipulated to determine its significance in individuals with ASD. To outline the important issues that would be required to design such a study, a group of clinicians, research scientists, and parents of children with ASD participated in an interdisciplinary daylong workshop as an extension of the 1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism (www.microbiome-autism.com). The group considered several aspects of designing clinical studies, including clinical trial design, treatments that could potentially be used in a clinical trial, appropriate ASD participants for the clinical trial, behavioral and cognitive assessments, important biomarkers, safety concerns, and ethical considerations. Overall, the group not only felt that this was a promising area of research for the ASD population and a promising avenue for potential treatment but also felt that further basic and translational research was needed to clarify the clinical utility of such treatments and to elucidate possible mechanisms responsible for a clinical response, so that new treatments and approaches may be discovered and/or fostered in the future.}, }
@article {pmid25955501, year = {2015}, author = {Tian, H and Ding, C and Gong, J and Wei, Y and McFarland, LV and Li, N}, title = {Freeze-dried, Capsulized Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {49}, number = {6}, pages = {537-538}, doi = {10.1097/MCG.0000000000000330}, pmid = {25955501}, issn = {1539-2031}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; *Freeze Drying ; Humans ; Middle Aged ; Recurrence ; }, }
@article {pmid25954111, year = {2015}, author = {Rossen, NG and MacDonald, JK and de Vries, EM and D'Haens, GR and de Vos, WM and Zoetendal, EG and Ponsioen, CY}, title = {Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review.}, journal = {World journal of gastroenterology}, volume = {21}, number = {17}, pages = {5359-5371}, pmid = {25954111}, issn = {2219-2840}, mesh = {Chi-Square Distribution ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Gastrointestinal Diseases/diagnosis/microbiology/*therapy ; Humans ; Intestines/*microbiology ; *Microbiota ; Risk Factors ; Treatment Outcome ; }, abstract = {AIM: To study the clinical efficacy and safety of Fecal microbiota transplantation (FMT). We systematically reviewed FMT used as clinical therapy.<br><br>METHODS: We searched MEDLINE, EMBASE, the Cochrane Library and Conference proceedings from inception to July, 2013. Treatment effect of FMT was calculated as the percentage of patients who achieved clinical improvement per patient category, on an intention-to-treat basis.<br><br>RESULTS: We included 45 studies; 34 on Clostridium difficile-infection (CDI), 7 on inflammatory bowel disease, 1 on metabolic syndrome, 1 on constipation, 1 on pouchitis and 1 on irritable bowel syndrome (IBS). In CDI 90% resolution of diarrhea in 33 case series (n = 867) was reported, and 94% resolution of diarrhea after repeated FMT in a randomized controlled trial (RCT) (n = 16). In ulcerative colitis (UC) remission rates of 0% to 68% were found (n = 106). In Crohn's disease (CD) (n = 6), no benefit was observed. In IBS, 70% improvement of symptoms was found (n = 13). 100% Reversal of symptoms was observed in constipation (n = 3). In pouchitis, none of the patients (n = 8) achieved remission. One RCT showed significant improvement of insulin sensitivity in metabolic syndrome (n = 10). Serious adverse events were rare.<br><br>CONCLUSION: FMT is highly effective in CDI, and holds promise in UC. As for CD, chronic constipation, pouchitis and IBS data are too limited to draw conclusions. FMT increases insulin sensitivity in metabolic syndrome.}, }
@article {pmid25954097, year = {2015}, author = {Koshino, K and Kanai, N and Yamato, M and Okano, T and Yamamoto, M}, title = {Novel isolated cecal pouch model for endoscopic observation in rats.}, journal = {World journal of gastroenterology}, volume = {21}, number = {17}, pages = {5242-5249}, pmid = {25954097}, issn = {2219-2840}, mesh = {Anastomosis, Surgical ; Anastomotic Leak/etiology/pathology ; Animals ; Cecum/pathology/*surgery ; Cells, Cultured ; Colon/surgery ; Defecation ; *Endoscopy, Gastrointestinal ; Epithelial Cells/transplantation ; Green Fluorescent Proteins/biosynthesis/genetics ; Ileum/surgery ; Intestinal Mucosa/pathology/*surgery ; Intestinal Obstruction/etiology/pathology ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Animal ; Rats, Inbred F344 ; Rats, Nude ; *Surgically-Created Structures/adverse effects ; Suture Techniques ; Ulcer/pathology ; }, abstract = {AIM: To create a new rat model for drug administration, cell transplantation, and endoscopic examination for the treatment of intestinal diseases.<br><br>METHODS: F344/NJc l-rnu/rnu rats (10-wk-old males, 350-400 g) were used in this study. The rats were anesthetized via 2% isoflurane inhalation. The rat's cecum was isolated from the intestines, and a pouch was created. The remainder of the intestines was rejoined to create an anastomosis. The "side-to-side" anastomosis (SSA) technique initially involves the creation of a 2-cm longitudinal incision into each intestinal wall. To create an anastomosis along the ileal and colonic walls, both intestines were cut, and a continuous suture procedure was performed that included all layers of both intestines. The serous membrane was sutured along the edge and on the anterior wall of the anastomosis. The "end-to-end" anastomosis (EEA) technique was compared with the SSA technique. In the EEA technique, the frontal surfaces of both cut intestinal lumens were joined together by continuous sutures. Additional sutures were made at the serosa. After the anastomotic intestine was successfully constructed, the two intestinal lumens that were cut at the isolated cecum were managed. In addition, one luminal side of the pouch remained open to create an artificial anus on the dorsum as a passage for the residual substances in the pouch. Finally, small animal endoscopy was used to observe the inside of the pouch.<br><br>RESULTS: In this animal model, mucus and feces are excreted through the reconstructed passage. Accordingly, the cecal pouch mucosa was not obstructed or contaminated by feces, thus facilitating observations of the luminal surface of the intestine. The endoscopic observation of the cecal pouch provided clear visualization given the absence of feces. The membrane surface of the cecum was clearly observed. Two methods of creating an anastomotic intestine, the "SSA" and "EEA" techniques, were compared with regard to animal survival rate, complication rate, and operation time. The SSA technique resulted in a significantly increased survival rate and a lower incidence of complications in rat models compared with the EEA technique. The complications of stenosis and leakage resulted in death in the EEA technique. Thus, the EEA technique exhibited a lower survival rate compared with the SSA technique. However, the SSA technique required a significantly longer operation time compared with the EEA technique.<br><br>CONCLUSION: Our new rat model is potentially useful for the development of a novel treatment for intestinal diseases.}, }
@article {pmid25947205, year = {2015}, author = {Lagier, JC and Delord, M and Million, M and Parola, P and Stein, A and Brouqui, P and Raoult, D}, title = {Dramatic reduction in Clostridium difficile ribotype 027-associated mortality with early fecal transplantation by the nasogastric route: a preliminary report.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {34}, number = {8}, pages = {1597-1601}, pmid = {25947205}, issn = {1435-4373}, mesh = {Aged ; Aged, 80 and over ; Clostridioides difficile/*classification/genetics/isolation &amp; purification ; Clostridium Infections/epidemiology/microbiology/*mortality/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; France/epidemiology ; Humans ; Incidence ; Male ; Prospective Studies ; *Ribotyping ; *Secondary Prevention ; Survival Analysis ; Treatment Outcome ; }, abstract = {Clostridium difficile ribotype 027 (CD027)-associated diarrhea preferentially affects elderly patients and causes a high mortality rate. Fecal microbiota transplantation has become an alternative treatment for recurrent C. difficile infections. An outbreak of CD027 infections has occurred in Marseille since March 2013. From March to November 2013, we treated patients using only antibiotics or fecal microbiota transplantation after at least three relapses. Beginning in November 2013, we performed early transplantation using a nasogastric tube during the first week of infection, in combination with antibiotic treatment. Sixty-one patients with a mean age of 84 years were hospitalized, including 42 patients treated only with antibiotics, three with tardive transplantation, and 16 with early transplantation. The patients were comparable in clinical involvement. The global mortality rate was 3/16 (18.75 %) among the patients treated by early transplantation and 29/45 (64.4 %) among the patients only treated by antibiotics or by tardive transplantation (p < 0.01). Among these 45 patients, 23 (51 %) died at day 31, including 17 who died at day 7. Early fecal transplantation was associated with a significantly reduced mortality rate, with only one patient dead at day 31 (6.25 %). In a Cox model, early transplantation was the only independent predictor of survival (hazard ratio 0.18, 95 % confidence interval 0.05-0.61, p = 0.006). Six of the 16 patients (37.5 %) needed a second transplantation before symptom resolution. Early fecal microbiota transplantation in combination with antibiotics should be the first-line treatment for CD027 infections.}, }
@article {pmid25946407, year = {2015}, author = {Kelly, CR}, title = {Editorial: a simple faecal preparation protocol for faecal microbiota transplantation.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {41}, number = {3}, pages = {320}, doi = {10.1111/apt.13039}, pmid = {25946407}, issn = {1365-2036}, mesh = {Clostridium Infections/*therapy ; Colon/*microbiology ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; }, }
@article {pmid25945590, year = {2015}, author = {Satokari, R and Mattila, E and Kainulainen, V and Arkkila, PE}, title = {Editorial: a simple faecal preparation for faecal microbiota transplantation--authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {41}, number = {3}, pages = {321}, doi = {10.1111/apt.13045}, pmid = {25945590}, issn = {1365-2036}, mesh = {Clostridium Infections/*therapy ; Colon/*microbiology ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; }, }
@article {pmid25945268, year = {2015}, author = {Jehangir, A and Bennett, K and Fareedy, SB and Rettew, A and Shaikh, B and Qureshi, A and Jehangir, Q and Alweis, R}, title = {Recurrent C. difficile in a Patient with IgG Deficiency.}, journal = {Case reports in gastrointestinal medicine}, volume = {2015}, number = {}, pages = {356293}, pmid = {25945268}, issn = {2090-6528}, abstract = {IgG deficiency can predispose to recurrent pyogenic infections. The association of IgG deficiency with Clostridium difficile infection has been infrequently reported in the literature. We present a case of a middle-age woman with multiple hospitalizations for recurrent C. difficile in a short span of time which prompted consideration of a possible fecal transplant. On evaluation, she was found to have low total IgG, with subclass analysis revealing low IgG1 and IgG3. She was started on monthly infusions of immunoglobulins and one year after her last episode of C. difficile she has not had any recurrence. The role of immunoglobulin infusion in the treatment of recurrent C. difficile is controversial, with some studies revealing no clear evidence of benefit. Our case report suggests that the patients who have underlying IgG deficiency may benefit from immunoglobulin, as this can significantly reduce the incidence of recurrent infections and hence save the healthcare costs.}, }
@article {pmid25942309, year = {2015}, author = {Costello, SP and Chung, A and Andrews, JM and Fraser, RJ}, title = {Fecal Microbiota Transplant for Clostridium difficile Colitis-Induced Toxic Megacolon.}, journal = {The American journal of gastroenterology}, volume = {110}, number = {5}, pages = {775-777}, pmid = {25942309}, issn = {1572-0241}, mesh = {Aged ; Biological Therapy/*methods ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/complications/*therapy ; Feces/*microbiology ; Female ; Humans ; Megacolon, Toxic/microbiology/*therapy ; Microbiota ; }, }
@article {pmid25939043, year = {2015}, author = {Suskind, DL}, title = {Reply to can fecal microbial transplant effectively treat Crohn's disease?.}, journal = {Inflammatory bowel diseases}, volume = {21}, number = {6}, pages = {E8}, doi = {10.1097/MIB.0000000000000410}, pmid = {25939043}, issn = {1536-4844}, mesh = {*Biological Therapy ; Crohn Disease/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; }, abstract = {Article first published online 29 April 2015.}, }
@article {pmid25938997, year = {2015}, author = {Surawicz, CM}, title = {Fecal microbiota transplantation: what we know and what we need to know.}, journal = {Annals of internal medicine}, volume = {162}, number = {9}, pages = {662-663}, doi = {10.7326/M15-0609}, pmid = {25938997}, issn = {1539-3704}, mesh = {Biological Therapy/*methods ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Feces/*microbiology ; Humans ; *Microbiota ; }, }
@article {pmid25938992, year = {2015}, author = {Drekonja, D and Reich, J and Gezahegn, S and Greer, N and Shaukat, A and MacDonald, R and Rutks, I and Wilt, TJ}, title = {Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review.}, journal = {Annals of internal medicine}, volume = {162}, number = {9}, pages = {630-638}, doi = {10.7326/M14-2693}, pmid = {25938992}, issn = {1539-3704}, mesh = {Biological Therapy/*methods ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Feces/*microbiology ; Humans ; *Microbiota ; Recurrence ; }, abstract = {BACKGROUND: The role of fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) is not well-known.<br><br>PURPOSE: To assess the efficacy, comparative effectiveness, and harms of FMT for CDI.<br><br>DATA SOURCES: MEDLINE (1980 to January 2015), Cochrane Library, and ClinicalTrials.gov, followed by hand-searching references from systematic reviews and identified studies.<br><br>STUDY SELECTION: Any study of FMT to treat adult patients with CDI; case reports were only used to report harms.<br><br>DATA EXTRACTION: Data were extracted by 1 author and verified by another; 2 authors independently assessed risk of bias and strength of evidence.<br><br>DATA SYNTHESIS: Two randomized, controlled trials (RCTs); 28 case-series studies; and 5 case reports were included. Two RCTs and 21 case-series studies (516 patients receiving FMT) reported using FMT for patients with recurrent CDI. A high proportion of treated patients had symptom resolution; however, the role of previous antimicrobials is unclear. One RCT comparing FMT with 2 control groups (n = 43) reported resolution of symptoms in 81%, 31%, and 23% of the FMT, vancomycin, or vancomycin-plus-bowel lavage groups, respectively (P < 0.001 for both control groups vs. FMT). An RCT comparing FMT route (n = 20) reported no difference between groups (60% in the nasogastric tube group and 80% in the colonoscopy group; P = 0.63). Across all studies for recurrent CDI, symptom resolution was seen in 85% of cases. In 7 case-series studies of patients with refractory CDI, symptom resolution ranged from 0% to 100%. Among 7 patients treated with FMT for initial CDI, results were mixed.<br><br>LIMITATION: Most studies were uncontrolled case-series studies; only 2 RCTs were available for analysis.<br><br>CONCLUSION: Fecal microbiota transplantation may have a substantial effect with few short-term adverse events for recurrent CDI. Evidence is insufficient on FMT for refractory or initial CDI treatment and on whether effects vary by donor, preparation, or delivery method.<br><br>PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.}, }
@article {pmid25937624, year = {2015}, author = {,  and Pucciani, F and Altomare, DF and Dodi, G and Falletto, E and Frasson, A and Giani, I and Martellucci, J and Naldini, G and Piloni, V and Sciaudone, G and ,  and Bove, A and Bocchini, R and Bellini, M and Alduini, P and Battaglia, E and Galeazzi, F and Rossitti, P and Usai Satta, P}, title = {Diagnosis and treatment of faecal incontinence: Consensus statement of the Italian Society of Colorectal Surgery and the Italian Association of Hospital Gastroenterologists.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {47}, number = {8}, pages = {628-645}, doi = {10.1016/j.dld.2015.03.028}, pmid = {25937624}, issn = {1878-3562}, mesh = {Anal Canal/surgery ; Antidiarrheals/therapeutic use ; Colorectal Surgery ; Electric Stimulation Therapy ; Fecal Incontinence/*diagnosis/etiology/physiopathology/surgery/*therapy ; Humans ; Intussusception/surgery ; Italy ; Laxatives/therapeutic use ; Quality of Life ; Rectal Prolapse/surgery ; Severity of Illness Index ; }, abstract = {Faecal incontinence is a common and disturbing condition, which leads to impaired quality of life and huge social and economic costs. Although recent studies have identified novel diagnostic modalities and therapeutic options, the best diagnostic and therapeutic approach is not yet completely known and shared among experts in this field. The Italian Society of Colorectal Surgery and the Italian Association of Hospital Gastroenterologists selected a pool of experts to constitute a joint committee on the basis of their experience in treating pelvic floor disorders. The aim was to develop a position paper on the diagnostic and therapeutic aspects of faecal incontinence, to provide practical recommendations for a cost-effective diagnostic work-up and a tailored treatment strategy. The recommendations were defined and graded on the basis of levels of evidence in accordance with the criteria of the Oxford Centre for Evidence-Based Medicine, and were based on currently published scientific evidence. Each statement was drafted through constant communication and evaluation conducted both online and during face-to-face working meetings. A brief recommendation at the end of each paragraph allows clinicians to find concise responses to each diagnostic and therapeutic issue.}, }
@article {pmid25937259, year = {2015}, author = {Kabar, I and Hüsing, A and Cicinnati, VR and Heitschmidt, L and Beckebaum, S and Thölking, G and Schmidt, HH and Karch, H and Kipp, F}, title = {Analysis of bile colonization and intestinal flora may improve management in liver transplant recipients undergoing ERCP.}, journal = {Annals of transplantation}, volume = {20}, number = {}, pages = {249-255}, doi = {10.12659/AOT.893549}, pmid = {25937259}, issn = {2329-0358}, mesh = {Adult ; Aged ; Bile/*microbiology ; *Cholangiopancreatography, Endoscopic Retrograde ; Drug Resistance, Bacterial ; Escherichia coli/isolation &amp; purification ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Klebsiella/isolation &amp; purification ; *Liver Transplantation ; Male ; Middle Aged ; Prospective Studies ; }, abstract = {BACKGROUND: Immunosuppression, denervation of biliary tract, and presence of biliary strictures favor colonization of bile with microorganisms after liver transplantation. Little is known about spectrum and antibiotic susceptibility of this colonization.<br><br>MATERIAL AND METHODS: Bile and feces were collected prospectively from 38 patients who underwent endoscopic retrograde cholangiopancreaticography after liver transplantation. Samples were analyzed for colonization and antibiotic susceptibility.<br><br>RESULTS: From the 38 tested bile samples, 86.6% tested positive. Of those, 26 (78.8%) were polymicrobial. Of isolated bile samples, 52 (64.2%) were gram-positive, 22.2% were gram-negative, and 13.6% revealed Candida albicans. Most detectable gram-positive bacteria were Enterococcus faecium. Most detectable gram-negative bacteria were E. coli and Klebsiella pneumonia. Our analyses revealed high resistance rates of the isolates. Only 55.6% of isolates were sensitive to ciprofloxacin, 54% were sensitive to piperacillin/tazobactam, and 60.3% were sensitive to imipenem. High susceptibility rates were found for linezolid and vancomycin (72.9% and 72.6%, respectively). We found a high correlation between microorganisms found in bile and those isolated from stool.<br><br>CONCLUSIONS: Bile of liver transplant recipients is frequently colonized with microorganisms. The starting point of this colonization is usually the intestine. Systematic analysis of bile colonization during endoscopic interventions on biliary tracts of liver transplant recipients might help to select effective prophylactic antibiotic regimes as well as to facilitate the choice of suitable antimicrobial therapy in case of septic complications.}, }
@article {pmid25933394, year = {2015}, author = {Dai, C and Jiang, M and Sun, MJ}, title = {Can fecal microbial transplant effectively treat Crohn's disease?.}, journal = {Inflammatory bowel diseases}, volume = {21}, number = {6}, pages = {E8}, pmid = {25933394}, issn = {1536-4844}, mesh = {*Biological Therapy ; Crohn Disease/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; }, abstract = {Article first published online 29 April 2015.}, }
@article {pmid25922340, year = {2015}, author = {van Olden, C and Groen, AK and Nieuwdorp, M}, title = {Role of Intestinal Microbiome in Lipid and Glucose Metabolism in Diabetes Mellitus.}, journal = {Clinical therapeutics}, volume = {37}, number = {6}, pages = {1172-1177}, doi = {10.1016/j.clinthera.2015.03.008}, pmid = {25922340}, issn = {1879-114X}, mesh = {Animals ; Diabetes Mellitus, Type 2/*metabolism ; Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Glucose/*metabolism ; Humans ; Inflammation/metabolism ; Insulin Resistance ; *Lipid Metabolism ; Obesity/metabolism ; }, abstract = {PURPOSE: The contribution of intestinal bacterial strains (gut microbiota) in human metabolism and obesity is being increasingly recognized. The goal of this article was to provide a commentary on the clinical usefulness of these data.<br><br>METHODS: We performed a review of the currently available articles on PubMed.<br><br>FINDINGS: Because most of the data are based on germ-free animal research, translation to human disease may be difficult. However, changes in the intestinal bacterial composition and subsequent altered diversity have been associated with the presence of chronic low-grade inflammation, a known feature of insulin resistance and type 2 diabetes mellitus.<br><br>IMPLICATIONS: It is still not proven whether intestinal bacteria play a causal role in glucose and lipid metabolism. Intervention studies including fecal transplantation and supplementation of single bacterial strains in humans might provide more insight. Moreover, prospective cohorts of healthy subjects using fecal samples collected at baseline can help to identify causally involved specific intestinal bacterial strains that drive aberrant human metabolism. Ultimately, it would be a great asset if potential diagnostic and therapeutic targets could be derived from this novel player in human cardiometabolism.}, }
@article {pmid25917784, year = {2015}, author = {Powell, N and Lo, JW and Biancheri, P and Vossenkämper, A and Pantazi, E and Walker, AW and Stolarczyk, E and Ammoscato, F and Goldberg, R and Scott, P and Canavan, JB and Perucha, E and Garrido-Mesa, N and Irving, PM and Sanderson, JD and Hayee, B and Howard, JK and Parkhill, J and MacDonald, TT and Lord, GM}, title = {Interleukin 6 Increases Production of Cytokines by Colonic Innate Lymphoid Cells in Mice and Patients With Chronic Intestinal Inflammation.}, journal = {Gastroenterology}, volume = {149}, number = {2}, pages = {456-67.e15}, pmid = {25917784}, issn = {1528-0012}, support = {WT088747MA/WT_/Wellcome Trust/United Kingdom ; MR/K002996/1/MRC_/Medical Research Council/United Kingdom ; MR/J006742/1/MRC_/Medical Research Council/United Kingdom ; G0802068/MRC_/Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; 098051/WT_/Wellcome Trust/United Kingdom ; WT101159AIA/WT_/Wellcome Trust/United Kingdom ; 098051/MRC_/Medical Research Council/United Kingdom ; 091009/WT_/Wellcome Trust/United Kingdom ; G0800746/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; CD3 Complex/metabolism ; CD4 Antigens/*metabolism ; Cell Culture Techniques ; Colon/cytology/immunology ; Cytokines/*metabolism ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Immunity, Innate/*drug effects ; Inflammatory Bowel Diseases/drug therapy/*immunology ; Interferon-gamma/metabolism ; Interleukin-17/metabolism ; Interleukin-1alpha/metabolism ; Interleukin-23/metabolism ; Interleukin-6/administration &amp; dosage/*pharmacology ; Interleukins/metabolism ; Lymphocytes/*drug effects/immunology ; Mice ; Mice, Knockout ; Receptors, Natural Cytotoxicity Triggering/metabolism ; Interleukin-22 ; }, abstract = {BACKGROUND &amp; AIMS: Innate lymphoid cells (ILCs) are a heterogeneous group of mucosal inflammatory cells that participate in chronic intestinal inflammation. We investigated the role of interleukin 6 (IL6) in inducing activation of ILCs in mice and in human beings with chronic intestinal inflammation.<br><br>METHODS: ILCs were isolated from colons of Tbx21(-/-)&#xa0;&#xd7; Rag2(-/-) mice (TRUC), which develop colitis; patients with inflammatory bowel disease (IBD); and patients without colon inflammation (controls). ILCs were characterized by flow cytometry; cytokine production was measured by enzyme-linked immunosorbent assay and cytokine bead arrays. Mice were given intraperitoneal injections of depleting (CD4, CD90), neutralizing (IL6), or control antibodies. Isolated colon tissues were analyzed by histology, explant organ culture, and cell culture. Bacterial DNA was extracted from mouse fecal samples to assess the intestinal microbiota.<br><br>RESULTS: IL17A- and IL22-producing, natural cytotoxicity receptor-negative, ILC3 were the major subset of ILCs detected in colons of TRUC mice. Combinations of IL23 and IL1&#x3b1; induced production of cytokines by these cells, which increased further after administration of IL6. Antibodies against IL6 reduced colitis in TRUC mice without significantly affecting the structure of their intestinal microbiota. Addition of IL6 increased production of IL17A, IL22, and interferon-&#x3b3; by human intestinal CD3-negative, IL7-receptor-positive cells, in a dose-dependent manner.<br><br>CONCLUSIONS: IL6 contributes to activation of colonic natural cytotoxicity receptor-negative, CD4-negative, ILC3s in mice with chronic intestinal inflammation (TRUC mice) by increasing IL23- and IL1&#x3b1;-induced production of IL17A and IL22. This pathway might be targeted to treat patients with IBD because IL6, which is highly produced in colonic tissue by some IBD patients, also increased the production of IL17A, IL22, and interferon-&#x3b3; by cultured human colon CD3-negative, IL7-receptor-positive cells.}, }
@article {pmid25917533, year = {2015}, author = {Kaiser, AM and Hogen, R and Bordeianou, L and Alavi, K and Wise, PE and Sudan, R and , }, title = {Clostridium Difficile Infection from a Surgical Perspective.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {19}, number = {7}, pages = {1363-1377}, pmid = {25917533}, issn = {1873-4626}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacterial Vaccines/therapeutic use ; *Clostridioides difficile ; *Colectomy ; Colitis/drug therapy ; Enterocolitis, Pseudomembranous/complications/*diagnosis/epidemiology/microbiology/*therapy ; Fecal Microbiota Transplantation ; Humans ; Ileostomy ; Immunoglobulins, Intravenous/therapeutic use ; Infection Control/methods ; Inflammatory Bowel Diseases/complications ; Risk Factors ; }, abstract = {BACKGROUND: The incidence and the severity of Clostridium difficile infection (CDI) have increased significantly over the last decade, especially in high-risk populations such as patients with inflammatory bowel disease (IBD). Surgeons must be able to both identify and minimize the risk of CDI in their own surgical patients and determine which CDI patients will benefit from surgery.<br><br>PURPOSE: We sought to define the risk factors, compare the treatment options, define the surgical indications, and identify factors that affect surgical outcomes for CDI based on the currently available literature.<br><br>RESULTS: Antibiotic use, exposure to the C. difficile bacteria, IBD, and higher levels of co-morbidity are all risk factors for CDI. The majority of CDI can be treated with antibiotics. Severe or fulminant colitis, however, has a high potential for poor outcome, but experience and some data suggest a lower mortality rate with colectomy rather than with continued medical treatment. Open total abdominal colectomy with end ileostomy is typically the preferred surgical strategy. It is often difficult to determine which patients will fail medical management as some may not manifest clinical signs of severe infection. Surrogate parameters of failure of medical therapy include respiratory and/or renal insufficiency, age greater than 60 years, peripheral vascular disease, congestive heart failure, and coagulopathy, all of which have been associated with worse surgical outcomes. Evidence suggests that in appropriately selected patients, colectomy performed before the development of shock requiring vasopressors, respiratory failure, renal failure, multi-organ dysfunction, and mental status changes may reduce mortality of the most severe forms of colitis. For less severe or recurrent presentations, creation of a loop ileostomy with intra-operative colonic lavage, fecal microbiota transfer, and C. difficile vaccinations are being discussed but have only been studied in small case-controlled series.<br><br>CONCLUSIONS: Prevention, containment, and non-surgical treatment are the cornerstone of management for CDI. However, the most severe forms with toxic colitis benefit from involvement of a surgical team. Swift open total abdominal colectomy with end ileostomy in patients with severe or fulminant C. difficile colitis has the best chance to reduce mortality if it is not delayed until shock, end organ damage, vasopressor requirement, mental status changes develop. Less aggressive approaches may be appropriate for milder and refractory forms but require further study before their applicability can be determined.}, }
@article {pmid25917520, year = {2015}, author = {Hajela, N and Ramakrishna, BS and Nair, GB and Abraham, P and Gopalan, S and Ganguly, NK}, title = {Gut microbiome, gut function, and probiotics: Implications for health.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {34}, number = {2}, pages = {93-107}, pmid = {25917520}, issn = {0975-0711}, mesh = {Digestive System Diseases/etiology/prevention &amp; control/therapy ; Endocrine System Diseases/etiology/prevention &amp; control/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Immune System Diseases/etiology/prevention &amp; control/therapy ; Metabolic Diseases/etiology/prevention &amp; control/therapy ; Metagenomics ; Nervous System Diseases/etiology/prevention &amp; control/therapy ; Probiotics/*therapeutic use ; }, abstract = {New insights from a rapidly developing field of research have ushered in a new era of understanding of the complexity of host-microbe interactions within the human body. The paradigm shift from culturing to metagenomics has provided an insight into the complex diversity of the microbial species that we harbor, revealing the fact that we are in fact more microbes than human cells. The largest consortium of these microbes resides in the gut and is called the gut microbiota. This new science has expanded the ability to document shifts in microbial populations to an unparalleled degree. It is now understood that signals from the microbiota provide trophic, nutritional, metabolic, and protective effects for the development and maintenance of the host digestive, immune, and neuroendocrine system. Evidence linking changes in the gut microbiota to gastrointestinal and extraintestinal disorders like irritable bowel syndrome, inflammatory bowel disease, obesity, diabetes, and celiac disease have begun to emerge recently. Probiotics act through diverse mechanisms positively affecting the composition and/or function of the commensal microbiota and alter host immunological responses. Well-controlled intervention trials, systematic reviews, and meta-analysis provide convincing evidence for the benefit of probiotics in prevention and treatment of gastrointestinal as well as extraintestinal disorders.}, }
@article {pmid25916464, year = {2015}, author = {Nakajima, K and Sueki, Y and Koshiishi, M and Kawashima, I and Nozaki, Y and Mitsumori, T and Kirito, K}, title = {Gastric invasion of multiple myeloma presenting as gastrointestinal bleeding.}, journal = {International journal of hematology}, volume = {101}, number = {6}, pages = {525-526}, pmid = {25916464}, issn = {1865-3774}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Blood Transfusion ; Dexamethasone/therapeutic use ; Doxorubicin/therapeutic use ; Female ; Humans ; Melena/diagnosis/*etiology/pathology/*therapy ; Melphalan/therapeutic use ; Middle Aged ; Multiple Myeloma/*complications/diagnosis/pathology/*therapy ; Stem Cell Transplantation ; Stomach/drug effects/*pathology ; Vincristine/therapeutic use ; }, }
@article {pmid25913649, year = {2015}, author = {Lagier, JC and Million, M and Fournier, PE and Brouqui, P and Raoult, D}, title = {Faecal microbiota transplantation for stool decolonization of OXA-48 carbapenemase-producing Klebsiella pneumoniae.}, journal = {The Journal of hospital infection}, volume = {90}, number = {2}, pages = {173-174}, doi = {10.1016/j.jhin.2015.02.013}, pmid = {25913649}, issn = {1532-2939}, mesh = {Cross Infection/*epidemiology ; *Disease Outbreaks ; Female ; Humans ; Infection Control/*methods ; Klebsiella Infections/*epidemiology ; Klebsiella pneumoniae/*enzymology ; Male ; beta-Lactamases/*metabolism ; }, }
@article {pmid25912469, year = {2015}, author = {Esposito, S and Umbrello, G and Castellazzi, L and Principi, N}, title = {Treatment of Clostridium difficile infection in pediatric patients.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {9}, number = {6}, pages = {747-755}, doi = {10.1586/17474124.2015.1039988}, pmid = {25912469}, issn = {1747-4132}, mesh = {Adolescent ; Age Factors ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Child ; Child, Preschool ; Clostridioides difficile/*pathogenicity ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Humans ; Infant ; Intestines/*microbiology ; Probiotics/adverse effects/*therapeutic use ; Risk Factors ; Treatment Outcome ; }, abstract = {Clostridium difficile causes infections that can either remain asymptomatic or manifest as clinical disease. In this report, problems, possible solutions, and future perspectives on the treatment of C. difficile infections (CDIs) in pediatric patients are discussed. CDI, despite increasing as a consequence of the overuse and misuse of antibiotics, remains relatively uncommon in pediatrics mainly because younger children are poorly susceptible to the action of C. difficile toxins. In most such cases, C. difficile disease is mild to moderate and discontinuation of the administered antibiotics in patients receiving these drugs when CDI develops, or administration of metronidazole, is sufficient to solve this problem. In severe or frequently relapsing cases, vancomycin is the drug of choice. Probiotics do not seem to add significant advantages. Other treatment options must be reserved for severe cases and be considered as a salvage treatment, although potential advantages in pediatric patients remain unclear.}, }
@article {pmid25905546, year = {2015}, author = {Vandenplas, Y and Pierard, D and De Greef, E}, title = {Fecal Microbiota Transplantation: Just a Fancy Trend?.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {61}, number = {1}, pages = {4-7}, doi = {10.1097/MPG.0000000000000816}, pmid = {25905546}, issn = {1536-4801}, mesh = {Adult ; Child ; *Clostridioides difficile ; Diarrhea/etiology/therapy ; Enterocolitis, Pseudomembranous/complications/microbiology/*therapy ; *Fecal Microbiota Transplantation/methods ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {The risks and advantages of the administration of fecal material of healthy people to patients are heavily debated. In adults, recurrent Clostridium difficile has become an accepted indication. In addition to all of the possible indications, many other questions need to be answered before pediatric indications and recommendations can be established. Optimal donor selection, fresh versus frozen stools versus capsules containing only microbiota, volume, and route of administration are just a few examples of the areas with missing data to allow in formulating recommendations for fecal microbiota or fecal material administration in children. A careful but not-too-complex regulation is the first priority in order to minimize the risk of administration of fecal slurry from unselected donors at home without medical supervision.}, }
@article {pmid25903104, year = {2015}, author = {Nagy-Szakal, D and Mir, SA and Harris, RA and Dowd, SE and Yamada, T and Lacorazza, HD and Tatevian, N and Smith, CW and de Zoeten, EF and Klein, J and Kellermayer, R}, title = {Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {29}, number = {8}, pages = {3151-3159}, pmid = {25903104}, issn = {1530-6860}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; P30 DK56338/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Colitis/*metabolism ; Colon/metabolism ; Diet ; Fatty Acids, Omega-6/*metabolism ; Intestinal Mucosa/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pediatric Obesity/*metabolism ; Prospective Studies ; }, abstract = {Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases (IBDs): Crohn disease (CD) and ulcerative colitis (UC). Dietary n-6 fatty acids have been associated with UC in prospective studies. However, the critical developmental period when (n-6) consumption may induce UC is not known. We examined the effects of transiently increased n-6 consumption during pediatric development on subsequent dextran-sulfate-sodium (DSS)-induced acute murine colitis. The animals transiently became obese then rapidly lost this phenotype. Interestingly, mice were protected against DSS colitis 40 days after n-6 consumption. The transient high n-6-induced protection against colitis was fat type- and dietary reversal-dependent and could be transferred to germ-free mice by fecal microbiota transplantation. We also detected decreased numbers of chemokine receptor (Cxcr)5(+) CD4(+) T cells in the mesenteric lymph nodes (MLNs) of transiently n-6-fed mice. Further experiments revealed that anti-chemokine ligand (Cxcl)13 (the ligand of Cxcr5) antibody treatment decreased DSS colitis severity, implicating the importance of the Cxcr5-Cxcl13 pathway in mammalian colitis. Consecutively, we found elevated CXCL13 concentrations (CD: 1.8-fold, P = 0.0077; UC: 1.9-fold, P = 0.056) in the serum of untreated pediatric IBD patients. The human serologic observations supported the translational relevance of our findings.}, }
@article {pmid25900952, year = {2015}, author = {Kim, YG and Jang, BI}, title = {Current advances related to Clostridium difficile infection.}, journal = {The Indian journal of medical research}, volume = {141}, number = {2}, pages = {172-174}, pmid = {25900952}, issn = {0975-9174}, mesh = {Clostridioides difficile/immunology/pathogenicity ; Clostridium Infections/immunology/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Humans ; *Immunity, Cellular ; Metronidazole/therapeutic use ; Risk Factors ; Vancomycin/therapeutic use ; }, abstract = {Clostridium difficile infection (CDI) can trigger various responses, ranging from asymptomatic carriage to fulminant colitis. Hard-to-cure CDI, such as severe CDI, multiple recurrences of CDI, refractory CDI, and hypervirulent strains of C. difficile, require new treatments, although antibiotics such as metronidazole and vancomycin are the treatment of choice for initial and first relapsing CDI. Active immunization with C. difficile toxins and faecal microbiota transplantation deserve special attention. Here we describe these strategies for difficult-to-treat CDI.}, }
@article {pmid25896342, year = {2015}, author = {Ho, JT and Chan, GC and Li, JC}, title = {Systemic effects of gut microbiota and its relationship with disease and modulation.}, journal = {BMC immunology}, volume = {16}, number = {}, pages = {21}, pmid = {25896342}, issn = {1471-2172}, mesh = {Animals ; Autoimmune Diseases/immunology/*therapy ; Dysbiosis/*immunology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Humans ; Intestinal Mucosa/*immunology/microbiology ; Mental Disorders/immunology/*therapy ; Neoplasms/immunology/*therapy ; Prebiotics ; Probiotics/therapeutic use ; Synbiotics ; }, abstract = {The gut microbiota makes up the majority of the human bacterial population, and although the gut microbiota resides in the intestines, it is able to exert systemic effects. Therefore, many diseases and conditions could be impacted by the gut microbiota when its composition is imbalanced, otherwise known as dysbiosis. However, apart from understanding the illnesses, we must also try to understand the intestinal flora itself to move forward and develop potential treatments.}, }
@article {pmid25895282, year = {2015}, author = {Marcos, LA and Gersh, A and Blanchard, K and Foil, S and Mallini, B and Farrell, SE and Kahler, R}, title = {Fecal transplantation to treat initial severe Clostridium difficile infection with sepsis.}, journal = {Journal of the Mississippi State Medical Association}, volume = {56}, number = {2}, pages = {38-40}, pmid = {25895282}, issn = {0026-6396}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous/epidemiology/*therapy ; Feces/*microbiology ; Humans ; Hypotension ; Intensive Care Units ; Male ; *Microbiota ; Middle Aged ; Sepsis/epidemiology/*therapy ; Transplantation/*methods ; }, }
@article {pmid25894269, year = {2015}, author = {Svačina, &#x160;}, title = {[The microbial flora in the digestive tract and diabetes].}, journal = {Vnitrni lekarstvi}, volume = {61}, number = {4}, pages = {361-364}, pmid = {25894269}, issn = {0042-773X}, mesh = {Diabetes Mellitus/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Microbiota ; }, abstract = {The microbial flora in the digestive tract has been recently studied in relation to metabolic diseases. There are relations to both type 1 diabetes and type 2 diabetes. The intestinal flora is affected by diet, physical exercise and it significantly changes after bariatric surgeries. Giving birth by caesarean section affects the gut flora development and increases the risk of type 1 diabetes in further life of the child. Obese patients with type 2 diabetes may lack protective microbes which improve glucoregulation in the experiment or on the contrary their patogenous microbes may grow which have been proven to even be able to penetrate into abdominal adipose tissue and play a role, inter alia, in the hepatic impairment and systemic inflammation. Also vaccination against these microbes is under consideration. Microbiome can be also positively affected by metformin treatment. The transfer of intestinal flora by means of fecal transplantation can improve glucoregulation. The influencing of intestinal flora is likely to become a new mechanism of diabetes treatment.}, }
@article {pmid25893454, year = {2015}, author = {Mittal, C and Miller, N and Meighani, A and Hart, BR and John, A and Ramesh, M}, title = {Fecal microbiota transplant for recurrent Clostridium difficile infection after peripheral autologous stem cell transplant for diffuse large B-cell lymphoma.}, journal = {Bone marrow transplantation}, volume = {50}, number = {7}, pages = {1010}, pmid = {25893454}, issn = {1476-5365}, mesh = {Clostridioides difficile/*virology ; Fecal Microbiota Transplantation/*methods ; Humans ; Lymphoma, Large B-Cell, Diffuse/*therapy ; Male ; Middle Aged ; Stem Cell Transplantation/*adverse effects/methods ; Transplantation, Autologous/*adverse effects/methods ; }, }
@article {pmid25885020, year = {2015}, author = {Hirsch, BE and Saraiya, N and Poeth, K and Schwartz, RM and Epstein, ME and Honig, G}, title = {Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent Clostridium difficile infection.}, journal = {BMC infectious diseases}, volume = {15}, number = {}, pages = {191}, pmid = {25885020}, issn = {1471-2334}, mesh = {Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Capsules ; Clostridioides difficile/isolation &amp; purification/pathogenicity ; Clostridium Infections/microbiology/pathology/*prevention &amp; control ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Humans ; Intestines/*microbiology ; Male ; Microbiota ; Middle Aged ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI), a complication of antibiotic-induced injury to the gut microbiome, is a prevalent and dangerous cause of infectious diarrhea. Antimicrobial therapy for CDI is typically effective for acute symptoms, but up to one third of patients later experience recurrent CDI. Fecal-derived microbiota transplantation (FMT) can ameliorate the underlying dysbiosis and is highly effective for recurrent CDI. Traditional methods of FMT are limited by patient discomfort, risk and inefficient procedures. Many individuals with recurrent CDI have extensive comorbidities and advanced age. Widespread use of FMT requires strategies that are non-invasive, scalable and applicable across healthcare settings.<br><br>METHODS: A method to facilitate microbiota transfer was developed. Fecal samples were collected and screened for potential pathogens. Bacteria were purified, concentrated, cryopreserved and formulated into multi-layered capsules. Capsules were administered to patients with recurrent CDI, who were then monitored for 90 days.<br><br>RESULTS: Thirteen women and six men with recurrent CDI were provided with microbiota transfer with orally administered capsules. The procedure was well tolerated. Thirteen individuals responded to a single course. Four patients were cured after a second course. There were 2 failures. The cumulative clinical cure rate of 89% is similar to the rates achieved with reported fecal-derived transplantation procedures.<br><br>CONCLUSIONS: Recurrent CDI represents a profound dysbiosis and a debilitating chronic disease. Stable cure can be achieved by restoring the gut microbiome with an effective, well-tolerated oral capsule treatment. This strategy of microbiota transfer can be widely applied and is particularly appropriate for frail patients.}, }
@article {pmid25882354, year = {2015}, author = {Feghoul, L and Chevret, S and Cuinet, A and Dalle, JH and Ouachée, M and Yacouben, K and Fahd, M and Guérin-El Khourouj, V and Roupret-Serzec, J and Sterkers, G and Baruchel, A and Simon, F and LeGoff, J}, title = {Adenovirus infection and disease in paediatric haematopoietic stem cell transplant patients: clues for antiviral pre-emptive treatment.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {21}, number = {7}, pages = {701-709}, doi = {10.1016/j.cmi.2015.03.011}, pmid = {25882354}, issn = {1469-0691}, mesh = {Adenoviridae Infections/diagnosis/*epidemiology/*prevention &amp; control ; Antiviral Agents/*therapeutic use ; Chemoprevention/methods ; Child ; Child, Preschool ; Feces/virology ; Female ; *Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Longitudinal Studies ; Male ; Risk Factors ; *Transplant Recipients ; Viral Load ; Viremia/diagnosis/*epidemiology/*prevention &amp; control ; }, abstract = {Human adenovirus (HAdV) infections constitute a major cause of morbidity in paediatric haematopoietic stem cell transplant (HSCT) patients. New antiviral treatments offer promising perspectives. However, it remains challenging to identify patients at risk for disseminated infection, and who should receive early antiviral intervention. We conducted a longitudinal study of allogeneic HSCT recipients, including weekly HAdV monitoring, to determine the risks factors associated with HAdV infection and dissemination, and to assess whether HAdV loads in stools may be used as surrogate markers for HAdV dissemination. Between September 2010 and December 2011, out of 72 patients, the cumulative incidence rates at day 100 of HAdV digestive infection, systemic infection and related disease were 35.9%, 24.0%, and 18.3%, respectively. In multivariate analysis, the risk factors for HAdV digestive and systemic infection were cord blood and in vitro T-cell depletion. Graft-versus-host disease (GVHD) grade >2 was also associated with systemic infection. In patients with HAdV digestive shedding, GVHD grade >2 and HAdV load in stools were the only risk factors for systemic infection. The median peak levels of HAdV in stool were 7.9 and 4.0 log10 copies/mL, respectively, in patients with HAdV systemic infection and in those without. HAdV monitoring in stools of paediatric HSCT recipients receiving cord blood or in vitro T-cell depleted transplants helps to predict patients at risk for HAdV systemic infection. Our results provide a rationale for randomized controlled trials to evaluate the benefit of anti-HAdV pre-emptive treatments based on HAdV DNA levels in stools.}, }
@article {pmid25881250, year = {2015}, author = {Li, Q and Wang, C and Tang, C and He, Q and Zhao, X and Li, N and Li, J}, title = {Successful treatment of severe sepsis and diarrhea after vagotomy utilizing fecal microbiota transplantation: a case report.}, journal = {Critical care (London, England)}, volume = {19}, number = {1}, pages = {37}, pmid = {25881250}, issn = {1466-609X}, mesh = {Adult ; Diarrhea/etiology/*therapy ; Dysbiosis/diagnosis/microbiology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Intestines/microbiology ; RNA, Ribosomal, 16S/analysis ; Sepsis/microbiology/*therapy ; *Vagotomy ; }, abstract = {INTRODUCTION: Dysbiosis of intestinal microbiota likely plays an important role in the development of gut-derived infections, making it a potential therapeutic target against sepsis. However, experience with fecal microbiota transplantation (FMT) in the treatment of sepsis and knowledge of the underlying mechanisms are extremely lacking. In this article, we describe a case of a patient who developed sepsis after a vagotomy and later received an infusion of donor feces microbiota, and we report our findings.<br><br>METHODS: A 44-year-old woman developed septic shock and severe watery diarrhea 4 days after undergoing a vagotomy. Antibiotics, probiotics and supportive treatment strategies were used for about 30 day after surgery, but the patient's fever, bacteremia and watery diarrhea persisted. Considering the possibility of intestinal dysbiosis, we evaluated the structure and composition of the patient's fecal microbiota using 16S rDNA-based molecular techniques. As expected, the gut microbiota was extensively disrupted; therefore, a donor fecal suspension was delivered into the patient by nasoduodenal tube. The patient's clinical outcomes and shifts of the gut microbiota following the treatment were also determined.<br><br>RESULTS: Dramatically, the patient's septic symptoms and severe diarrhea were successfully controlled following FMT. Her stool output markedly declined after 7 days and normalized 16 days after FMT. A significant modification in her microbiota composition was consistently seen, characterized by a profound enrichment of the commensals in Firmicutes and depletion of opportunistic organisms in Proteobacteria. Furthermore, we identified a reconstituted bacterial community enriched in Firmicutes and depleted of Proteobacteria members that was associated with fecal output, plasma markers of inflammation and T helper cells.<br><br>CONCLUSIONS: In this report, we describe our initial experience with FMT, in which we successfully used it in the treatment of a patient with sepsis and severe diarrhea after a vagotomy. Our data indicate an association between repaired intestinal microbiota barrier and improvement of clinical outcomes. Our patient's surprising clinical benefits from FMT demonstrate the role of intestinal microbiota in modulating immune equilibrium. It represents a breakthrough in the clinical management of sepsis and suggests new therapeutic avenues to pursue for microbiota-related indications.}, }
@article {pmid25878340, year = {2015}, author = {Crum-Cianflone, NF and Sullivan, E and Ballon-Landa, G}, title = {Fecal microbiota transplantation and successful resolution of multidrug-resistant-organism colonization.}, journal = {Journal of clinical microbiology}, volume = {53}, number = {6}, pages = {1986-1989}, pmid = {25878340}, issn = {1098-660X}, mesh = {Aged ; *Clostridioides difficile/drug effects ; *Drug Resistance, Multiple, Bacterial ; *Enterocolitis, Pseudomembranous/microbiology/therapy ; Fatal Outcome ; *Fecal Microbiota Transplantation ; Humans ; Male ; }, abstract = {We report a case in which fecal microbiota transplantation (FMT) utilized for relapsing Clostridium difficile colitis successfully eradicated colonization with several multidrug-resistant organisms (MDROs). FMT may have an additive benefit of reducing MDRO carriage and should be further investigated as a potential measure to eradicate additional potentially virulent organisms beyond C. difficile.}, }
@article {pmid25874537, year = {2015}, author = {Liu, A and Weiss, S and Fang, H and Claus, RA and Rödel, J and Dirsch, O and Dahmen, U}, title = {Lipopolysaccharide-binding protein (LBP) blockade augments the protective effect of granulocyte colony-stimulating factor (G-CSF) in a rat sepsis model.}, journal = {Shock (Augusta, Ga.)}, volume = {43}, number = {5}, pages = {497-503}, doi = {10.1097/SHK.0000000000000338}, pmid = {25874537}, issn = {1540-0514}, mesh = {Acute-Phase Proteins/*chemistry ; Animals ; Carrier Proteins/*chemistry ; Feces ; Granulocyte Colony-Stimulating Factor/administration &amp; dosage/*chemistry ; Humans ; Inflammation ; Male ; Membrane Glycoproteins/*chemistry ; NF-kappa B/metabolism ; Neutrophils/immunology/pathology ; Peptides/administration &amp; dosage ; Rats ; Rats, Inbred Lew ; STAT3 Transcription Factor/metabolism ; Sepsis/immunology/physiopathology ; Time Factors ; Treatment Outcome ; Up-Regulation ; }, abstract = {The effect of granulocyte colony-stimulating factor (G-CSF) on sepsis is discussed controversially in clinical studies. We previously demonstrated that G-CSF treatment induced lipopolysaccharide (LPS) sensitization via up-regulation of LPS-binding protein (LBP). We hypothesized that the futile effect of G-CSF-treatment in sepsis might be due to its ability to up-regulate LBP. Therefore, blockade of LBP may attenuate the G-CSF-induced LPS sensitization and protect animals from polymicrobial sepsis. Endogenous LBP levels were up-regulated by pretreatment with G-CSF, and the LBP protein was blocked by administration of a specific blocking peptide-LBPK95A. Polymicrobial sepsis was induced by intraperitoneal injection of feces slurry. Rats were monitored every 3 up to 72 h to observe the survival rate. Tissue injury, bacterial infiltration, local inflammatory response, and neutrophil infiltration at 0, 2, and 12 h after the septic insult were analyzed. The survival benefit of G-CSF pretreatment was improved when combined with LBPK95A treatment (control vs. G-CSF vs. combi: 36% vs. 56% vs. 93%; P < 0.05). Combined treatment of G-CSF and LBPK95A was associated with the minimal tissue damage. Treatment with LBPK95A significantly inhibited the neutrophil infiltration without interfering with the bacterial clearance. The G-CSF-induced inflammatory sensitization effect was inhibited by LBPK95A, indicated by the decrease of cytokines expression, and the activation of nuclear factor kappa B and signal transducer and activator of transcription 3 signaling pathway. In conclusion, these results suggested that the effect of prophylactic augmentation of the host's response via G-CSF pretreatment was further enhanced by inhibition of the up-regulation of LBP.}, }
@article {pmid25867688, year = {2015}, author = {Adachi, K and Suemizu, H and Murayama, N and Shimizu, M and Yamazaki, H}, title = {Human biofluid concentrations of mono(2-ethylhexyl)phthalate extrapolated from pharmacokinetics in chimeric mice with humanized liver administered with di(2-ethylhexyl)phthalate and physiologically based pharmacokinetic modeling.}, journal = {Environmental toxicology and pharmacology}, volume = {39}, number = {3}, pages = {1067-1073}, doi = {10.1016/j.etap.2015.02.011}, pmid = {25867688}, issn = {1872-7077}, mesh = {Administration, Oral ; Animals ; Diethylhexyl Phthalate/*administration &amp; dosage/*analogs &amp; derivatives/pharmacokinetics/urine ; Feces/chemistry ; Humans ; Liver/*metabolism ; Liver Transplantation ; Mice ; }, abstract = {Di(2-ethylhexyl)phthalate (DEHP) is a reproductive toxicant in male rodents. The aim of the current study was to extrapolate the pharmacokinetics and toxicokinetics of mono(2-ethylhexyl)phthalate (MEHP, a primary metabolite of DEHP) in humans by using data from oral administration of DEHP to chimeric mice transplanted with human hepatocytes. MEHP and its glucuronide were detected in plasma from control mice and chimeric mice after single oral doses of 250mg DEHP/kg body weight. Biphasic plasma concentration-time curves of MEHP and its glucuronide were seen only in control mice. MEHP and its glucuronide were extensively excreted in urine within 24h in mice with humanized liver. In contrast, fecal excretion levels of MEHP glucuronide were high in control mice compared with those with humanized liver. Adjusted animal biomonitoring equivalents from chimeric mice studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Estimated urine MEHP concentrations in humans were consistent with reported concentrations. This research illustrates how chimeric mice transplanted with human hepatocytes in combination with a simple PBPK model can assist evaluations of pharmacokinetics or toxicokinetics of the primary or secondary metabolites of DEHP.}, }
@article {pmid25857665, year = {2015}, author = {Moayyedi, P and Surette, MG and Kim, PT and Libertucci, J and Wolfe, M and Onischi, C and Armstrong, D and Marshall, JK and Kassam, Z and Reinisch, W and Lee, CH}, title = {Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial.}, journal = {Gastroenterology}, volume = {149}, number = {1}, pages = {102-109.e6}, doi = {10.1053/j.gastro.2015.04.001}, pmid = {25857665}, issn = {1528-0012}, mesh = {Adult ; Aged ; Biological Therapy/*methods ; Colitis, Ulcerative/physiopathology/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; Middle Aged ; Remission Induction ; }, abstract = {BACKGROUND &amp; AIMS: Ulcerative colitis (UC) is difficult to treat, and standard therapy does not always induce remission. Fecal microbiota transplantation (FMT) is an alternative approach that induced remission in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled randomized trial.<br><br>METHODS: We performed a parallel study of patients with active UC without infectious diarrhea. Participants were examined by flexible sigmoidoscopy when the study began and then were randomly assigned to groups that received FMT (50 mL, via enema, from healthy anonymous donors; n = 38) or placebo (50 mL water enema; n = 37) once weekly for 6 weeks. Patients, clinicians, and investigators were blinded to the groups. The primary outcome was remission of UC, defined as a Mayo score &#x2264;2 with an endoscopic Mayo score of 0, at week 7. Patients provided stool samples when the study began and during each week of FMT for microbiome analysis. The trial was stopped early for futility by the Data Monitoring and Safety Committee, but all patients already enrolled in the trial were allowed to complete the study.<br><br>RESULTS: Seventy patients completed the trial (3 dropped out from the placebo group and 2 from the FMT group). Nine patients who received FMT (24%) and 2 who received placebo (5%) were in remission at 7 weeks (a statistically significant difference in risk of 17%; 95% confidence interval, 2%-33%). There was no significant difference in adverse events between groups. Seven of the 9 patients in remission after FMT received fecal material from a single donor. Three of the 4 patients with UC &#x2264;1 year entered remission, compared with 6 of 34 of those with UC >1 year (P = .04, Fisher's exact test). Stool from patients receiving FMT had greater microbial diversity, compared with baseline, than that of patients given the placebo (P = .02, Mann-Whitney U test).<br><br>CONCLUSIONS: FMT induces remission in a significantly greater percentage of patients with active UC than placebo, with no difference in adverse events. Fecal donor and time of UC appear to affect outcomes. ClinicalTrials.gov Number: NCT01545908.}, }
@article {pmid25853207, year = {2015}, author = {Kellermayer, R and Nagy-Szakal, D and Harris, RA and Luna, RA and Pitashny, M and Schady, D and Mir, SA and Lopez, ME and Gilger, MA and Belmont, J and Hollister, EB and Versalovic, J}, title = {Serial fecal microbiota transplantation alters mucosal gene expression in pediatric ulcerative colitis.}, journal = {The American journal of gastroenterology}, volume = {110}, number = {4}, pages = {604-606}, pmid = {25853207}, issn = {1572-0241}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; U01 CA170930/CA/NCI NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Biological Therapy/*methods ; Colitis, Ulcerative/metabolism/*surgery ; *Colon ; *Feces/microbiology ; Female ; *Gene Expression Regulation ; Humans ; Intestinal Mucosa/*metabolism ; Male ; *Microbiota ; Transplantation, Homologous ; }, }
@article {pmid25853204, year = {2015}, author = {Stollman, N and Smith, M and Giovanelli, A and Mendolia, G and Burns, L and Didyk, E and Burgess, J and Noh, A and Edelstein, C and Alm, E and Kassam, Z}, title = {Frozen encapsulated stool in recurrent Clostridium difficile: exploring the role of pills in the treatment hierarchy of fecal microbiota transplant nonresponders.}, journal = {The American journal of gastroenterology}, volume = {110}, number = {4}, pages = {600-601}, pmid = {25853204}, issn = {1572-0241}, mesh = {Abdominal Pain/microbiology ; Aged ; Aged, 80 and over ; Aminoglycosides/administration &amp; dosage ; Anti-Bacterial Agents/*therapeutic use ; Biological Therapy/*methods ; Capsules ; Clostridioides difficile/*isolation &amp; purification ; *Colonoscopy ; Diarrhea/microbiology ; Drug Administration Schedule ; Enterocolitis, Pseudomembranous/drug therapy/*surgery ; *Feces/microbiology ; Female ; Fidaxomicin ; Freezing ; Humans ; Irritable Bowel Syndrome/*complications ; Male ; Metronidazole/administration &amp; dosage ; *Microbiota ; Recurrence ; Transplantation, Homologous ; Treatment Outcome ; Vancomycin/administration &amp; dosage ; }, }
@article {pmid25852213, year = {2015}, author = {Rosenfeld, CS}, title = {Microbiome Disturbances and Autism Spectrum Disorders.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {43}, number = {10}, pages = {1557-1571}, doi = {10.1124/dmd.115.063826}, pmid = {25852213}, issn = {1521-009X}, mesh = {Animals ; Autism Spectrum Disorder/diet therapy/immunology/*microbiology ; Dysbiosis/diet therapy/immunology/*microbiology ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/immunology/microbiology ; Humans ; Microbiota/physiology ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; }, abstract = {Autism spectrum disorders (ASDs) are considered a heterogenous set of neurobehavioral diseases, with the rates of diagnosis dramatically increasing in the past few decades. As genetics alone does not explain the underlying cause in many cases, attention has turned to environmental factors as potential etiological agents. Gastrointestinal disorders are a common comorbidity in ASD patients. It was thus hypothesized that a gut-brain link may account for some autistic cases. With the characterization of the human microbiome, this concept has been expanded to include the microbiota-gut-brain axis. There are mounting reports in animal models and human epidemiologic studies linking disruptive alterations in the gut microbiota or dysbiosis and ASD symptomology. In this review, we will explore the current evidence that gut dysbiosis in animal models and ASD patients correlates with disease risk and severity. The studies to date have surveyed how gut microbiome changes may affect these neurobehavioral disorders. However, we harbor other microbiomes in the body that might impact brain function. We will consider microbial colonies residing in the oral cavity, vagina, and the most recently discovered one in the placenta. Based on the premise that gut microbiota alterations may be causative agents in ASD, several therapeutic options have been tested, such as diet modulations, prebiotics, probiotics, synbiotics, postbiotics, antibiotics, fecal transplantation, and activated charcoal. The potential benefits of these therapies will be considered. Finally, the possible mechanisms by which changes in the gut bacterial communities may result in ASD and related neurobehavioral disorders will be examined.}, }
@article {pmid25850839, year = {2015}, author = {Oh, HK and Lee, HS and Lee, JH and Oh, SH and Lim, JY and Ahn, S and Hwang, JY and Kang, SB}, title = {Functional and histological evidence for the targeted therapy using biocompatible polycaprolactone beads and autologous myoblasts in a dog model of fecal incontinence.}, journal = {Diseases of the colon and rectum}, volume = {58}, number = {5}, pages = {517-525}, doi = {10.1097/DCR.0000000000000346}, pmid = {25850839}, issn = {1530-0358}, mesh = {Anal Canal/*injuries ; Animals ; Biocompatible Materials/*therapeutic use ; Cell Differentiation ; Disease Models, Animal ; Dogs ; Fecal Incontinence/*therapy ; Fluorescent Antibody Technique ; Manometry ; *Muscle Contraction ; Myoblasts, Skeletal/metabolism/*transplantation ; Myosin Heavy Chains/metabolism ; Polyesters/*therapeutic use ; Transplantation, Autologous ; Treatment Outcome ; }, abstract = {BACKGROUND: Injection of bulking agents into the anal canal is limited by several factors, including biological resorption, particle migration, and ongoing degradation of the injected bulking agent.<br><br>OBJECTIVE: We investigated whether an injection of polycaprolactone beads containing autologous myoblasts could improve sphincter function in a dog model of fecal incontinence.<br><br>DESIGN: The control sham surgery group underwent skin incision around the anal sphincter (n = 5). Fecal incontinence was induced by resecting 25% of the posterior internal/external anal sphincter in another 10 dogs. After 1 month of sphincter injury, dogs were then treated with (n = 5) or without (n = 5) polycaprolactone beads containing PKH-26-labeled autologous myoblasts.<br><br>SETTING: This study was conducted at the department of surgery in collaboration with the department of advanced materials.<br><br>OUTCOME MEASURES: Three months after injection treatment, the resting and contractile pressure differences of the anal sphincter were compared, and histopathological studies were performed.<br><br>RESULTS: The anal pressures in untreated dogs were significantly lower than those in the sham surgery group (p < 0.05). The resting and contractile pressure differences were higher in treated dogs than in untreated dogs (resting pressure difference: 0.7&#x2009;&#xb1;&#x2009;0.5 vs -0.6&#x2009;&#xb1;&#x2009;0.8 mmHg; coefficient of the difference in recovery rate, 0.38; 95% CI, 0.15-0.61, p = 0.001; contractile pressure difference: 1.1&#x2009;&#xb1;&#x2009;4.2 vs -3.9&#x2009;&#xb1;&#x2009;2.6 mmHg; coefficient, 1.63; 95% CI, 0.55-2.71, p = 0.003). Immunofluorescent staining confirmed that the myoblasts had differentiated and synthesized myosin heavy chain, as observed in vitro.<br><br>LIMITATIONS: This study was limited by the lack of comparison of injecting beads containing autologous myoblasts with injecting myoblasts alone.<br><br>CONCLUSION: This study shows that an injection of polycaprolactone beads containing autologous myoblasts may improve anal sphincter function in an animal model of fecal incontinence.}, }
@article {pmid25850838, year = {2015}, author = {Chandra, A and Mishra, B and Kumar, S and Gupta, V and Noushif, M and Ghoshal, UC and Misra, A and Srivastava, PK}, title = {Dynamic article: composite antropyloric valve and gracilis muscle transposition for total anorectal reconstruction: a preliminary report.}, journal = {Diseases of the colon and rectum}, volume = {58}, number = {5}, pages = {508-516}, doi = {10.1097/DCR.0000000000000319}, pmid = {25850838}, issn = {1530-0358}, mesh = {Adult ; Anal Canal/*abnormalities/injuries/*surgery ; Anorectal Malformations ; Anus, Imperforate/*surgery ; Carcinoma/*surgery ; Electric Stimulation Therapy ; Female ; Humans ; Male ; Manometry ; Middle Aged ; Muscle, Skeletal/*transplantation ; Perineum/injuries/*surgery ; Pylorus/*transplantation ; Plastic Surgery Procedures/*methods ; Rectal Neoplasms/*surgery ; Rectum/*abnormalities/*surgery ; Thigh ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Technique and functional outcomes of anorectal reconstruction using an antropyloric graft have been reported previously. This technique had reasonable initial outcomes but lacked voluntary function.<br><br>OBJECTIVE: We hereby report the initial results of patients who underwent gracilis muscle wrapping around the perineally transposed antropyloric valve in an attempt to improve voluntary fecal control.<br><br>SETTING: This study was conducted at a single tertiary care institution.<br><br>PATIENTS: Eight adult patients (7 men and 1 woman) with a median age of 38 years (range, 19-51 years) underwent this procedure. Seven patients already had anorectal reconstruction with a transposed antropyloric valve, and 1 patient with severely damaged anal sphincter complex underwent single-stage composite antropylorus transposition with a gracilis muscle wrap.<br><br>MAIN OUTCOME MEASURES: The primary outcome measures were anatomical integrity and functional status of the composite graft in the perineum.<br><br>RESULTS: No operative mortality or serious procedure-related morbidity occurred in any patient. The median postoperative resting pressure was 29 mmHg (range, 22-38 mmHg) and squeeze pressure was 72.5 mmHg (range, 45-267 mmHg). There was a significant improvement in the squeeze pressure following surgery (p = 0.039). Also, the St. Mark's incontinence scores significantly improved in all patients and varied between 7 and 9 (p = 0.003). The ability to defer defecation and the reduced frequency of leakage accidents were the prime reasons for improved postgraciloplasty outcomes in these patients. On personal interviews, all patients who underwent this procedure were satisfied with the results of their surgery.<br><br>LIMITATIONS: A longer follow-up with a larger sample size is required. Quality-of-life data have not been evaluated in this study.<br><br>CONCLUSIONS: Gracilis muscle wrapping around a perineally transposed antropyloric valve is possible and improves the voluntary control and overall functional outcomes in a select group of patients with end-stage fecal incontinence requiring anal replacement (Supplemental Digital Content 1, http://links.lww.com/DCR/A173).}, }
@article {pmid25843083, year = {2015}, author = {Orduna, P and Lopez, SY and Schmulson, M and Arredondo, R and Ponce de Leon, S and Lopez-Vidal, Y}, title = {A survey using the social networks revealed poor knowledge on fecal microbiota transplantation.}, journal = {Journal of neurogastroenterology and motility}, volume = {21}, number = {2}, pages = {294-295}, pmid = {25843083}, issn = {2093-0879}, }
@article {pmid25842815, year = {2015}, author = {Sato, T}, title = {[An essay about new therapies for the anorectal dysfunction].}, journal = {Nihon Geka Gakkai zasshi}, volume = {116}, number = {1}, pages = {55}, pmid = {25842815}, issn = {0301-4894}, mesh = {Digestive System Surgical Procedures/methods/trends ; Electric Stimulation Therapy ; Fecal Incontinence/*surgery ; Humans ; Lumbosacral Plexus ; Quality of Life ; Plastic Surgery Procedures/methods/trends ; Rectum/surgery/transplantation ; }, }
@article {pmid25836986, year = {2015}, author = {Rossen, NG and Fuentes, S and van der Spek, MJ and Tijssen, JG and Hartman, JH and Duflou, A and Löwenberg, M and van den Brink, GR and Mathus-Vliegen, EM and de Vos, WM and Zoetendal, EG and D'Haens, GR and Ponsioen, CY}, title = {Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis.}, journal = {Gastroenterology}, volume = {149}, number = {1}, pages = {110-118.e4}, doi = {10.1053/j.gastro.2015.03.045}, pmid = {25836986}, issn = {1528-0012}, mesh = {Adult ; Aged ; Biological Therapy/*methods ; Colitis, Ulcerative/*therapy ; Double-Blind Method ; Feces/*microbiology ; Female ; Humans ; Intubation, Gastrointestinal/statistics &amp; numerical data ; Male ; *Microbiota ; Middle Aged ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Several case series have reported the effects of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). We assessed the efficacy and safety of FMT for patients with UC in a double-blind randomized trial.<br><br>METHODS: Patients with mild to moderately active UC (n = 50) were assigned to groups that underwent FMT with feces from healthy donors or were given autologous fecal microbiota (control); each transplant was administered via nasoduodenal tube at the start of the study and 3 weeks later. The study was performed at the Academic Medical Center in Amsterdam from June 2011 through May 2014. The composite primary end point was clinical remission (simple clinical colitis activity index scores &#x2264;2) combined with &#x2265;1-point decrease in the Mayo endoscopic score at week 12. Secondary end points were safety and microbiota composition by phylogenetic microarray in fecal samples.<br><br>RESULTS: Thirty-seven patients completed the primary end point assessment. In the intention-to-treat analysis, 7 of 23 patients who received fecal transplants from healthy donors (30.4%) and 5 of 25 controls (20.0%) achieved the primary end point (P = .51). In the per-protocol analysis, 7 of 17 patients who received fecal transplants from healthy donors (41.2%) and 5 of 20 controls (25.0%) achieved the primary end point (P = .29). Serious adverse events occurred in 4 patients (2 in the FMT group), but these were not considered to be related to the FMT. At 12 weeks, the microbiota of responders in the FMT group was similar to that of their healthy donors; remission was associated with proportions of Clostridium clusters IV and XIVa.<br><br>CONCLUSIONS: In this phase 2 trial, there was no statistically significant difference in clinical and endoscopic remission between patients with UC who received fecal transplants from healthy donors and those who received their own fecal microbiota, which may be due to limited numbers. However, the microbiota of responders had distinct features from that of nonresponders, warranting further study. ClinicalTrials.gov Number: NCT01650038.}, }
@article {pmid25834446, year = {2015}, author = {Zhou, L and Foster, JA}, title = {Psychobiotics and the gut-brain axis: in the pursuit of happiness.}, journal = {Neuropsychiatric disease and treatment}, volume = {11}, number = {}, pages = {715-723}, pmid = {25834446}, issn = {1176-6328}, abstract = {The human intestine houses an astounding number and species of microorganisms, estimated at more than 10(14) gut microbiota and composed of over a thousand species. An individual's profile of microbiota is continually influenced by a variety of factors including but not limited to genetics, age, sex, diet, and lifestyle. Although each person's microbial profile is distinct, the relative abundance and distribution of bacterial species is similar among healthy individuals, aiding in the maintenance of one's overall health. Consequently, the ability of gut microbiota to bidirectionally communicate with the brain, known as the gut-brain axis, in the modulation of human health is at the forefront of current research. At a basic level, the gut microbiota interacts with the human host in a mutualistic relationship - the host intestine provides the bacteria with an environment to grow and the bacterium aids in governing homeostasis within the host. Therefore, it is reasonable to think that the lack of healthy gut microbiota may also lead to a deterioration of these relationships and ultimately disease. Indeed, a dysfunction in the gut-brain axis has been elucidated by a multitude of studies linked to neuropsychological, metabolic, and gastrointestinal disorders. For instance, altered microbiota has been linked to neuropsychological disorders including depression and autism spectrum disorder, metabolic disorders such as obesity, and gastrointestinal disorders including inflammatory bowel disease and irritable bowel syndrome. Fortunately, studies have also indicated that gut microbiota may be modulated with the use of probiotics, antibiotics, and fecal microbiota transplants as a prospect for therapy in microbiota-associated diseases. This modulation of gut microbiota is currently a growing area of research as it just might hold the key to treatment.}, }
@article {pmid25834343, year = {2015}, author = {Brechmann, T and Swol, J and Knop-Hammad, V and Willert, J and Aach, M and Cruciger, O and Schmiegel, W and Schildhauer, TA and Hamsen, U}, title = {Complicated fecal microbiota transplantation in a tetraplegic patient with severe Clostridium difficile infection.}, journal = {World journal of gastroenterology}, volume = {21}, number = {12}, pages = {3736-3740}, pmid = {25834343}, issn = {2219-2840}, mesh = {Aged ; Clostridioides difficile/*isolation &amp; purification ; Colonoscopy ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Humans ; Intestines/*microbiology ; Male ; *Microbiota ; Quadriplegia/*etiology ; Severity of Illness Index ; Spinal Cord Injuries/*complications ; Treatment Outcome ; }, abstract = {A 65-year-old male suffering from acute spinal cord injury leading to incomplete tetraplegia presented with severe recurrent Clostridium difficile (C. difficile) infection subsequent to antibiotic treatment for pneumonia. After a history of ineffective antimicrobial therapies, including metronidazole, vancomycin, fidaxomicin, rifaximin and tigecycline, leading to several relapses, the patient underwent colonoscopic fecal microbiota transplantation from his healthy son. Four days subsequent to the procedure, the patient showed a systemic inflammation response syndrome. Without detecting an infectious cause, the patient received antimicrobial treatment, including tigecycline, metronidazole, vancomycin via polyethylene glycol and an additional enema for a period of seven days, leading to a prompt recovery and no reported C. difficile infection relapse during a 12 wk follow up.}, }
@article {pmid25834008, year = {2015}, author = {Boyle, ML and Ruth-Sahd, LA and Zhou, Z}, title = {Fecal microbiota transplant to treat recurrent Clostridium difficile infections.}, journal = {Critical care nurse}, volume = {35}, number = {2}, pages = {51-64; quiz 65}, doi = {10.4037/ccn2015356}, pmid = {25834008}, issn = {1940-8250}, mesh = {Aged ; Clostridioides difficile/*isolation &amp; purification ; Emergency Service, Hospital ; Enterocolitis, Pseudomembranous/*diagnosis/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Recurrence ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {The prevalence of recurrent or refractory Clostridium difficile infection has been steadily increasing since 2000. Consequently, alternative treatments to the standard antibiotic therapies are now being considered. One alternative treatment is fecal microbiota transplant. Although fecal microbiota transplant is relatively new--and not appealing to most people--it has been around for many years and has great promise as an inexpensive, safe, and efficient treatment of refractory and recurrent C difficile infection. With a better understanding of the intricacies of the colonic microbiome and its role in colonic physiology and pathophysiology, critical care nurses will recognize that fecal microbiota transplant has the potential to become the standard of care for treatment of recurrent or refractory C difficile infection. The American College of Gastroenterology and the Infectious Diseases Society of America provide the latest treatment guidelines for care of patients with these clostridial infections.}, }
@article {pmid25832456, year = {2015}, author = {Gottardi, M and Paula, FM and Corral, MA and Meisel, DM and Costa, SF and Abdala, E and Pierrotti, LC and Yamashiro, J and Chieffi, PP and Gryschek, RC}, title = {Immunofluorescence assay for diagnosis of strongyloidiasis in immunocompromised patients.}, journal = {Infectious diseases (London, England)}, volume = {47}, number = {8}, pages = {550-554}, doi = {10.3109/23744235.2015.1028096}, pmid = {25832456}, issn = {2374-4243}, mesh = {Adolescent ; Adult ; Animals ; Antigens, Helminth/immunology/isolation &amp; purification ; Child ; Enzyme-Linked Immunosorbent Assay ; Feces/*parasitology ; Fluorescent Antibody Technique/*methods ; Fluorescent Antibody Technique, Indirect/*methods ; Humans ; *Immunocompromised Host ; Larva ; Male ; Middle Aged ; Sensitivity and Specificity ; Strongyloides stercoralis/isolation &amp; purification/pathogenicity ; Strongyloidiasis/*diagnosis ; Young Adult ; }, abstract = {BACKGROUND: Strongyloides stercoralis is a parasite that causes human strongyloidiasis. The disease ranges from asymptomatic to severe forms, which are often fatal in immunocompromised individuals. Laboratory diagnosis is challenging owing to limitations in the use of conventional parasitological techniques. The present study aimed to evaluate the indirect immunofluorescence assay (IFA) using infective larvae of S. venezuelensis as an antigen for the immunodiagnosis of human strongyloidiasis in immunocompromised patients.<br><br>METHODS: Serum and stool samples from 200 immunocompromised patients (HIV-positive, HTLV-1-positive, and renal, liver, and/or bone marrow transplantation candidates) were used. Stool samples were examined using three parasitological methods: Lutz, Rugai, and culture agar plate. IFA was performed using sections of infective larvae of S. venezuelensis as antigens, and showed 95.4% sensitivity and 95.8% and specificity.<br><br>RESULTS: Among the 200 patients, 17 (8.5%) were positive for S. stercoralis by at least one parasitological method, and 43 (21.5%) were positive by IFA.<br><br>CONCLUSIONS: IFA can be used as a screening method for the detection of S. stercoralis in immunocompromised patients.}, }
@article {pmid25829393, year = {2015}, author = {Mell, B and Jala, VR and Mathew, AV and Byun, J and Waghulde, H and Zhang, Y and Haribabu, B and Vijay-Kumar, M and Pennathur, S and Joe, B}, title = {Evidence for a link between gut microbiota and hypertension in the Dahl rat.}, journal = {Physiological genomics}, volume = {47}, number = {6}, pages = {187-197}, pmid = {25829393}, issn = {1531-2267}, support = {HL-020176/HL/NHLBI NIH HHS/United States ; DK-89503/DK/NIDDK NIH HHS/United States ; P30 DK089503/DK/NIDDK NIH HHS/United States ; HL-112641/HL/NHLBI NIH HHS/United States ; P30 DK020572/DK/NIDDK NIH HHS/United States ; DK-08194/DK/NIDDK NIH HHS/United States ; R01 HL112641/HL/NHLBI NIH HHS/United States ; P30 DK081943/DK/NIDDK NIH HHS/United States ; U24 DK097153/DK/NIDDK NIH HHS/United States ; DK-097153/DK/NIDDK NIH HHS/United States ; HL-076709/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Blood Pressure/drug effects ; Cecum/drug effects/microbiology/transplantation ; Fatty Acids/blood ; *Gastrointestinal Microbiome/drug effects ; Genetic Variation ; Genome ; Hypertension/blood/*microbiology/physiopathology ; Kaplan-Meier Estimate ; Longevity ; Metabolomics ; Rats, Inbred Dahl ; Sodium/blood/urine ; Systole/drug effects ; }, abstract = {The gut microbiota plays a critical role in maintaining physiological homeostasis. This study was designed to evaluate whether gut microbial composition affects hypertension. 16S rRNA genes obtained from cecal samples of Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats were sequenced. Bacteria of the phylum Bacteroidetes were higher in the S rats compared with the R rats. Furthermore, the family S24-7 of the phylum Bacteroidetes and the family Veillonellaceae of the phylum Firmicutes were higher in the S rats compared with the R rats. Analyses of the various phylogenetic groups of cecal microbiota revealed significant differences between S and R rats. Both strains were maintained on a high-salt diet, administered antibiotics for ablation of microbiota, transplanted with S or R rat cecal contents, and monitored for blood pressure (BP). Systolic BP of the R rats remained unaltered irrespective of S or R rat cecal transplantation. Surprisingly, compared with the S rats given S rat cecal content, systolic BP of the S rats given a single bolus of cecal content from R rats was consistently and significantly elevated during the rest of their life, and they had a shorter lifespan. A lower level of fecal bacteria of the family Veillonellaceae and increased plasma acetate and heptanoate were features associated with the increased BP observed in the S rats given R rat microbiota compared with the S rats given S rat microbiota. These data demonstrate a link between microbial content and BP regulation and, because the S and R rats differ in their genomic composition, provide the necessary basis to further examine the relationship between the host genome and microbiome in the context of BP regulation in the Dahl rats.}, }
@article {pmid25825673, year = {2015}, author = {Weingarden, A and González, A and Vázquez-Baeza, Y and Weiss, S and Humphry, G and Berg-Lyons, D and Knights, D and Unno, T and Bobr, A and Kang, J and Khoruts, A and Knight, R and Sadowsky, MJ}, title = {Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {10}, pmid = {25825673}, issn = {2049-2618}, support = {R21 AI091907/AI/NIAID NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) that often fails standard antibiotic therapy. Despite its widespread recent use, however, little is known about the stability of the fecal microbiota following FMT.<br><br>RESULTS: Here we report on short- and long-term changes and provide kinetic visualization of fecal microbiota composition in patients with multiply recurrent CDI that were refractory to antibiotic therapy and treated using FMT. Fecal samples were collected from four patients before and up to 151 days after FMT, with daily collections until 28 days and weekly collections until 84 days post-FMT. The composition of fecal bacteria was characterized using high throughput 16S rRNA gene sequence analysis, compared to microbiota across body sites in the Human Microbiome Project (HMP) database, and visualized in a movie-like, kinetic format. FMT resulted in rapid normalization of bacterial fecal sample composition from a markedly dysbiotic state to one representative of normal fecal microbiota. While the microbiome appeared most similar to the donor implant material 1 day post-FMT, the composition diverged variably at later time points. The donor microbiota composition also varied over time. However, both post-FMT and donor samples remained within the larger cloud of fecal microbiota characterized as healthy by the HMP.<br><br>CONCLUSIONS: Dynamic behavior is an intrinsic property of normal fecal microbiota and should be accounted for in comparing microbial communities among normal individuals and those with disease states. This also suggests that more frequent sample analyses are needed in order to properly assess success of FMT procedures.}, }
@article {pmid25825054, year = {2015}, author = {Batista, R and Kapel, N and Megerlin, F and Chaumeil, JC and Barbut, F and Bourlioux, P and Chast, F}, title = {[Fecal microbiota transplantation in recurrent Clostridium difficile infections. Framework and pharmaceutical preparation aspects].}, journal = {Annales pharmaceutiques francaises}, volume = {73}, number = {5}, pages = {323-331}, doi = {10.1016/j.pharma.2015.02.004}, pmid = {25825054}, issn = {0003-4509}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Microbiota ; }, abstract = {The fecal microbiota transplantation consists in introducing a preparation constituted by a dilution of stools of a healthy donor in the digestive tract of a patient recipient, to restore his intestinal physiological balance. This therapeutic approach was the subject of numerous studies showing its efficiency in the treatment of the recurrent infections with Clostridium difficile. The fecal microbiota transplantation has now a high level of clinical evidence, which explains that it appears in various international recommendations. In France, the fecal microbiota transplantation responds to the definition of a medication and can be executed as a pharmaceutical preparation or as an experimental drug for clinical trials under the responsibility of a hospital pharmacy. The objective of this paper is to propose a definition of a framework and to describe the methods of preparation of the fecal microbiota transplantation in the treatment of the recurrent infections with C. difficile and the interactions to consider for hospital pharmacies that do not have technical means to operate this technique.}, }
@article {pmid25823408, year = {2015}, author = {Meijer, RP and Mertens, LS and Meinhardt, W and Verwaal, VJ and Dik, P and Horenblas, S}, title = {The colon shuffle: A modified urinary diversion.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {41}, number = {9}, pages = {1264-1268}, doi = {10.1016/j.ejso.2015.02.007}, pmid = {25823408}, issn = {1532-2157}, mesh = {Adult ; Aged ; Cohort Studies ; Colon/*transplantation ; Colonic Diseases/*surgery ; Colostomy/*methods ; Cystectomy/methods ; Female ; Humans ; Male ; Middle Aged ; Netherlands ; Pelvic Exenteration/methods ; Rectal Diseases/*surgery ; Retrospective Studies ; Urinary Diversion/*methods ; Urologic Diseases/*surgery ; }, abstract = {AIM: To assess the results of a urinary diversion in patients who already have a colostomy or simultaneously require a (rectum) colon resection. The diversion is created from the distal part of the transected colon with a simultaneously created new colostomy contra-laterally (if necessary). This procedure is known in our institute as the 'colon shuffle'.<br><br>MATERIALS AND METHODS: All patients who underwent a colon shuffle in the period of 2003 and 2013 in our institute (Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital) were identified. Comorbidity was scored using the Charlson comorbidity index. Local or systemic treatment prior to surgery was reported (e.g. external beam radiotherapy, systemic chemotherapy). Surgical complications were reported according to the Clavien-Dindo classification.<br><br>RESULTS: Twenty-one patients (14 male; 7 female) underwent a colon shuffle procedure in our institute, with a mean age of 61.5 years. The majority (90.4%) of these patients had been subjected to radiotherapy on the pelvic region in the past. Although short-term complications (<30 days) were seen in 52.4% of these patients, major complications such as anastomotic leakage of the bowel and fecal peritonitis were not seen in this high-risk group of patients.<br><br>CONCLUSION: The colon shuffle offers an elegant solution for patients who require a urinary diversion simultaneously with a colostomy or for patients who already have a colostomy from previous surgery.}, }
@article {pmid25822774, year = {2015}, author = {Agilli, M and Ilga, U}, title = {A methodological approach to fecal microbial transplant via nasogastric tube for active pediatric ulcerative colitis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {60}, number = {4}, pages = {e36}, doi = {10.1097/MPG.0000000000000716}, pmid = {25822774}, issn = {1536-4801}, mesh = {Colitis, Ulcerative/*therapy ; Humans ; Male ; *Microbiota ; *Therapies, Investigational ; }, }
@article {pmid25819745, year = {2015}, author = {Cui, H and Bai, S and Huo, Z and Li, J and Sun, J and An, X}, title = {A cluster of rotavirus enteritis in pediatric liver recipients.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {17}, number = {3}, pages = {477-480}, doi = {10.1111/tid.12378}, pmid = {25819745}, issn = {1399-3062}, mesh = {Base Sequence ; Community-Acquired Infections ; Cross Infection ; Diarrhea ; Feces/virology ; Female ; Genotype ; Humans ; Infant ; Liver Transplantation/*adverse effects ; Male ; Molecular Sequence Data ; Phylogeny ; Rotavirus/genetics/*isolation &amp; purification ; Rotavirus Infections/*epidemiology/virology ; Sequence Analysis, DNA ; }, abstract = {We observed a cluster of 4 pediatric liver recipients who developed diarrhea in a liver transplant unit within 5 days. Feces from these 4 patients were rotavirus positive when tested with Colloidal Gold Diagnostic Kit. Nucleic acid from 3 fecal specimens was extracted and reverse transcribed. Two were amplified positively. The complementary DNAs were sequenced. Alignment and phylogenetic analysis were performed with MEGA 6.06. Although involving only 4 pediatric liver recipients, this cluster was caused by at least 2 distinct G9P[8] rotavirus strains and included community infection and nosocomial infection.}, }
@article {pmid25818484, year = {2015}, author = {He, C and Shan, Y and Song, W}, title = {Targeting gut microbiota as a possible therapy for diabetes.}, journal = {Nutrition research (New York, N.Y.)}, volume = {35}, number = {5}, pages = {361-367}, doi = {10.1016/j.nutres.2015.03.002}, pmid = {25818484}, issn = {1879-0739}, mesh = {Animals ; Diabetes Mellitus, Type 1/etiology/immunology/metabolism/*microbiology ; Diabetes Mellitus, Type 2/etiology/immunology/metabolism/*microbiology ; Dysbiosis/immunology/microbiology/physiopathology/*therapy ; Endotoxemia/etiology/prevention &amp; control ; Energy Metabolism ; *Evidence-Based Medicine ; *Fecal Microbiota Transplantation ; Gastroenteritis/etiology/prevention &amp; control ; *Gastrointestinal Microbiome/immunology ; Gastrointestinal Tract/immunology/metabolism/microbiology/physiopathology ; Humans ; Immunity, Innate ; Insulin Resistance ; *Models, Biological ; Permeability ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The incidence of diabetes has increased rapidly across the entire world in the last 2 decades. Accumulating evidence suggests that gut microbiota contribute to the pathogenesis of diabetes. Several studies have demonstrated that patients with diabetes are characterized by a moderate degree of gut microbial dysbiosis. However, there are still substantial controversies regarding altered composition of the gut microbiota and the underlying mechanisms by which gut microbiota interact with the body's metabolism. The purpose of this review is to define the association between gut microbiota and diabetes. In doing so an electronic search of studies published in English from January 2004 to the November 2014 in the National Library of Medicine, including the original studies that addressed the effects of gut microbiota on diabetes, energy metabolism, inflammation, the immune system, gut permeability and insulin resistance, was performed. Herein, we discuss the possible mechanisms by which the gut microbiota are involved in the development of diabetes, including energy metabolism, inflammation, the innate immune system, and the bowel function of the intestinal barrier. The compositional changes in the gut microbiota in type 2 and type 1 diabetes are also discussed. Moreover, we introduce the new findings of fecal transplantation, and use of probiotics and prebiotics as new treatment strategies for diabetes. Future research should be focused on defining the primary species of the gut microbiota and their exact roles in diabetes, potentially increasing the possibility of fecal transplants as a therapeutic strategy for diabetes.}, }
@article {pmid25815766, year = {2015}, author = {Lee, JR and Muthukumar, T and Dadhania, D and Taur, Y and Jenq, RR and Toussaint, NC and Ling, L and Pamer, E and Suthanthiran, M}, title = {Gut microbiota and tacrolimus dosing in kidney transplantation.}, journal = {PloS one}, volume = {10}, number = {3}, pages = {e0122399}, pmid = {25815766}, issn = {1932-6203}, support = {R37 AI051652/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K08-DK087824/DK/NIDDK NIH HHS/United States ; KL2 TR000458/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; KL2-TR000458/TR/NCATS NIH HHS/United States ; R37AI051652/AI/NIAID NIH HHS/United States ; UL1 TR000457/TR/NCATS NIH HHS/United States ; K08 DK087824/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/drug effects ; Dose-Response Relationship, Drug ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Graft Rejection/*drug therapy/genetics/microbiology ; Humans ; *Kidney Transplantation ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Tacrolimus/*administration &amp; dosage ; Transplant Recipients ; }, abstract = {Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5) or did not require such an increase (Dose Stable Group, n=14). We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2 ± 1.1 mg/day vs. 3.8 ± 0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts) but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6 ± 2.4 mg/day vs. 3.3 ± 1.5 mg/day, respectively, P<0.001). Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses). Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01) and had a coefficient ± standard error of 1.0 ± 0.6 (P=0.08) after multivariable linear regression. Our novel observations may help further explain inter-individual differences in tacrolimus dosing to achieve therapeutic levels.}, }
@article {pmid25808229, year = {2015}, author = {Sheehan, D and Moran, C and Shanahan, F}, title = {The microbiota in inflammatory bowel disease.}, journal = {Journal of gastroenterology}, volume = {50}, number = {5}, pages = {495-507}, pmid = {25808229}, issn = {1435-5922}, mesh = {Anti-Bacterial Agents/therapeutic use ; Body Mass Index ; Evidence-Based Medicine ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Genetic Predisposition to Disease ; Global Health ; Humans ; Incidence ; Inflammatory Bowel Diseases/epidemiology/genetics/*microbiology/*therapy ; Life Style ; *Microbiota ; Prevalence ; Probiotics/therapeutic use ; Risk Factors ; Treatment Outcome ; }, abstract = {This review explores our current understanding of the complex interaction between environmental risk factors, genetic traits and the development of inflammatory bowel disease. The primacy of environmental risk factors is illustrated by the rapid increase in the incidence of the disease worldwide. We discuss how the gut microbiota is the proximate environmental risk factor for subsequent development of inflammatory bowel disease. The evolving fields of virome and mycobiome studies will further our understanding of the full potential of the gut microbiota in disease pathogenesis. Manipulating the gut microbiota is a promising therapeutic avenue.}, }
@article {pmid25805941, year = {2015}, author = {Garcia-Olmo, D and Guadalajara, H and Rubio-Perez, I and Herreros, MD and de-la-Quintana, P and Garcia-Arranz, M}, title = {Recurrent anal fistulae: limited surgery supported by stem cells.}, journal = {World journal of gastroenterology}, volume = {21}, number = {11}, pages = {3330-3336}, pmid = {25805941}, issn = {2219-2840}, mesh = {Adipose Tissue/*cytology ; Adult ; Aged ; Cells, Cultured ; Compassionate Use Trials ; Crohn Disease/complications ; Fecal Incontinence/etiology ; Female ; Humans ; Male ; Middle Aged ; Rectal Fistula/diagnosis/etiology/*surgery ; Recurrence ; Reoperation ; Severity of Illness Index ; *Stem Cell Transplantation/adverse effects/methods ; Time Factors ; Transplantation, Autologous ; Treatment Outcome ; Wound Healing ; }, abstract = {AIM: To study the results of stem-cell therapy under a Compassionate-use Program for patients with recurrent anal fistulae.<br><br>METHODS: Under controlled circumstances, and approved by European and Spanish laws, a Compassionate-use Program allows the use of stem-cell therapy for patients with very complex anal fistulae. Candidates had previously undergone multiple surgical interventions that had failed to resolve the fistulae, and presented symptomatic recurrence. The intervention consisted of limited surgery (with closure of the internal opening), followed by local implant of stem cells in the fistula-tract wall. Autologous expanded adipose-derived stem cells were the main cell type selected for implant. The first evaluation was performed on the 8(th) postoperative week; outcome was classified as response or partial response. Evaluation one year after the intervention confirmed if complete healing of the fistula was achieved.<br><br>RESULTS: Ten patients (8 male) with highly recurrent and complex fistulae were treated (mean age: 49 years, range: 28-76 years). Seven cases were non-Crohn's fistulae, and three were Crohn's-associated fistulae. Previous surgical attempts ranged from 3 to 12. Two patients presented with preoperative incontinence (Wexner scores of 12 and 13 points). After the intervention, six patients showed clinical response on the 8(th) postoperative week, with a complete cessation of suppuration from the fistula. Three patients presented a partial response, with an evident decrease in suppuration. A year later, six patients (60%) remained healed, with complete reepithelization of the external opening. Postoperative Wexner Scores were 0 in six cases. The two patients with previous incontinence improved their scores from 12 to 8 points and from 13 to 5 points. No adverse reactions or complications related to stem-cell therapy were reported during the study period.<br><br>CONCLUSION: Stem cells are safe and useful for treating anal fistulae. Healing can be achieved in severe cases, sparing fecal incontinence risk, and improving previous scoring.}, }
@article {pmid25805532, year = {2015}, author = {Tauxe, WM and Dhere, T and Ward, A and Racsa, LD and Varkey, JB and Kraft, CS}, title = {Fecal microbiota transplant protocol for clostridium difficile infection.}, journal = {Laboratory medicine}, volume = {46}, number = {1}, pages = {e19-23}, pmid = {25805532}, issn = {1943-7730}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; }, mesh = {Clinical Protocols/*standards ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/*surgery ; Fecal Microbiota Transplantation/*methods/*standards ; Humans ; }, abstract = {Fecal microbiota transplant has become more acceptable as a therapeutic for recurrent Clostridium difficile infection. The FDA has an enforcement discretion policy for practitioner's performing this therapy, which includes informed consent for this experimental treatment. This manuscript describes a typical procedure that can be followed that includes the important aspects of this preparation and treatment.}, }
@article {pmid25805303, year = {2015}, author = {Baxter, M and Ahmad, T and Colville, A and Sheridan, R}, title = {Fatal Aspiration Pneumonia as a Complication of Fecal Microbiota Transplant.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {61}, number = {1}, pages = {136-137}, doi = {10.1093/cid/civ247}, pmid = {25805303}, issn = {1537-6591}, mesh = {Aged, 80 and over ; Fatal Outcome ; Fecal Microbiota Transplantation/*adverse effects ; Humans ; Pneumonia, Aspiration/*etiology/*pathology ; }, }
@article {pmid25798243, year = {2015}, author = {Wang, J and Xiao, Y and Lin, K and Song, F and Ge, T and Zhang, T}, title = {Pediatric severe pseudomembranous enteritis treated with fecal microbiota transplantation in a 13-month-old infant.}, journal = {Biomedical reports}, volume = {3}, number = {2}, pages = {173-175}, pmid = {25798243}, issn = {2049-9434}, abstract = {Fecal microbiota transplantation (FMT) is a procedure used to restore the intestinal microbiota of a diseased individual using indigenous intestinal microorganisms from a healthy donor. The current case report presents the first case of a 13-month-old male with severe pseudomembranous enteritis (PME) treated with FMT. The infant was admitted to Shanghai Children's Hospital with a 2-month history of diarrhea, and a 1.5-month history of retractable edema, hypoalbuminemia, electrolyte disturbance and malnutrition. Besides necessary nutritional support, the patient was treated twice with oral metronidazole combined with or without vancomycin. Diarrhea was partially remitted. However, the infant had bloody or dark-green feces, and a distended abdomen. On day 96 from the initiation of the disease, a single FMT via a nasal jejuna feeding tube was performed. From day 2 until 4 months post-FMT, the patient presented with no diarrhea, normal feces and a satisfactory weight. To the best of our knowledge, this is the first pediatric PME treated with FMT. The current data show that FMT is an efficient choice for recurrent clostridium difficile infection and PME in adults and a few pediatric cases. Due to a lack of safety and effectiveness data, treatment should be cautiously applied in the pediatric population.}, }
@article {pmid25798151, year = {2015}, author = {Dennis, M and Salpeter, MJ and Hota, S}, title = {Low awareness but positive attitudes toward fecal transplantation in Ontario physicians.}, journal = {The Canadian journal of infectious diseases &amp; medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale}, volume = {26}, number = {1}, pages = {30-32}, pmid = {25798151}, issn = {1712-9532}, abstract = {BACKGROUND: Despite mounting evidence supporting fecal transplantation (FT) as a treatment for recurrent Clostridium difficile infection (CDI), adoption into clinical practice has been slow.<br><br>OBJECTIVE: To determine the health literacy and attitudes of academic physicians in Toronto and infectious disease physicians in Ontario toward FT as a treatment for recurrent CDI, and to determine whether these are significant barriers to adoption.<br><br>METHODS: Surveys were distributed to 253 general internists, infectious diseases specialists, gastroenterologists and family physicians.<br><br>RESULTS: The response rate was 15%. More than 60% of physicians described themselves as being 'not at all' or 'somewhat' familiar with FT. Of the 76% of physicians who had never referred a patient for FT, the most common reason (50%) was lack of awareness of where to access the treatment. The 'ick factor' accounted for only 13% of reasons for not referring. No respondent believed that the procedure was too risky to consider.<br><br>CONCLUSION: Despite general poor health literacy on FT, most physicians sampled share similar positive attitudes toward the treatment.}, }
@article {pmid25788003, year = {2015}, author = {Ye, X and Van, JN and Munoz, FM and Revell, PA and Kozinetz, CA and Krance, RA and Atmar, RL and Estes, MK and Koo, HL}, title = {Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {15}, number = {7}, pages = {1874-1881}, pmid = {25788003}, issn = {1600-6143}, support = {K23 DK084513/DK/NIDDK NIH HHS/United States ; P01 AI057788/AI/NIAID NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; 1K23DK084513/DK/NIDDK NIH HHS/United States ; }, mesh = {Caliciviridae Infections/immunology/*virology ; Child ; Diarrhea/diagnosis/epidemiology/*virology ; Feces/chemistry/virology ; Female ; Follow-Up Studies ; Graft Rejection/etiology ; Graft Survival ; *Hematopoietic Stem Cell Transplantation ; Humans ; *Immunocompromised Host ; Male ; Norovirus/*isolation &amp; purification ; *Organ Transplantation ; Prognosis ; Prospective Studies ; RNA, Viral/genetics ; Risk Factors ; Texas/epidemiology ; Transplant Recipients ; }, abstract = {Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1-324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.}, }
@article {pmid25783387, year = {2015}, author = {Neuvonen, MI and Kyrklund, K and Lindahl, HG and Koivusalo, AI and Rintala, RJ and Pakarinen, MP}, title = {A population-based, complete follow-up of 146 consecutive patients after transanal mucosectomy for Hirschsprung disease.}, journal = {Journal of pediatric surgery}, volume = {50}, number = {10}, pages = {1653-1658}, doi = {10.1016/j.jpedsurg.2015.02.006}, pmid = {25783387}, issn = {1531-5037}, mesh = {Adolescent ; Adult ; Anal Canal/*surgery ; Child ; Child, Preschool ; Enterocolitis/etiology ; Female ; Follow-Up Studies ; Hirschsprung Disease/*surgery ; Humans ; Infant ; Male ; Postoperative Complications ; *Proctocolectomy, Restorative ; Rectum/*surgery ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: The objective of the study is to define the population-based bowel functional outcomes and enterocolitis following transanal endorectal pull-through (TEPT) in patients with Hirschsprung disease (HD) treated at our institution between 1986 and 2011.<br><br>METHODS: 146 consecutive patients who had undergone primary surgical treatment for HD were included. The median follow-up time was 15 (3-33) years. The clinical details and prevalence of enterocolitis were evaluated in all patients, and bowel function in patients >3 years of age with functional intestino-anal continuity.<br><br>RESULTS: No patients were lost to follow-up. Overall survival was 98%. The level of disease was rectosigmoid in 83%, long segment in 7%, total colonic in 4%, and extending up to the small bowel in 6%. 29% had an associated syndrome. 22% had a preoperative stoma. Operations included TEPT (89%), proctocolectomy with ileoanal anastomosis in 9%, and 3% had a permanent endostomy owing to small intestinal aganglionosis. One patient underwent intestinal transplantation. At the latest follow-up, 42% had occasional soiling, 12% had frequent soiling and 46% had no soiling. Constipation occurred in 9%. An associated syndrome was the only predictor for soiling or constipation (OR 4.3, 95% CI 1.5-12). 44% developed recurrent postoperative enterocolitis, which was predicted by extended aganglionosis (OR 6.9, 95% CI 2.4-20) and syndromatic disease (OR 2.4, 95% CI 1.2-5.0).<br><br>CONCLUSION: The major functional sequelae following TEPT were recurrent enterocolitis and fecal soiling, which was mostly occasional. An associated syndrome was a predictor of a reduced bowel functional outcome, and alongside extended aganglionosis were significant risk factors for recurrent postoperative enterocolitis.}, }
@article {pmid25782899, year = {2015}, author = {Varier, RU and Biltaji, E and Smith, KJ and Roberts, MS and Kyle Jensen, M and LaFleur, J and Nelson, RE}, title = {Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {Infection control and hospital epidemiology}, volume = {36}, number = {4}, pages = {438-444}, doi = {10.1017/ice.2014.80}, pmid = {25782899}, issn = {1559-6834}, mesh = {Adult ; Anti-Bacterial Agents/economics/therapeutic use ; Clostridioides difficile ; Cost Savings ; Cost-Benefit Analysis ; Drug Costs ; Enterocolitis, Pseudomembranous/drug therapy/economics/*therapy ; Fecal Microbiota Transplantation/*economics ; Health Care Costs ; Humans ; Quality-Adjusted Life Years ; Vancomycin/economics/therapeutic use ; }, abstract = {OBJECTIVE: Clostridium difficile infection (CDI) places a high burden on the US healthcare system. Recurrent CDI (RCDI) occurs frequently. Recently proposed guidelines from the American College of Gastroenterology (ACG) and the American Gastroenterology Association (AGA) include fecal microbiota transplantation (FMT) as a therapeutic option for RCDI. The purpose of this study was to estimate the cost-effectiveness of FMT compared with vancomycin for the treatment of RCDI in adults, specifically following guidelines proposed by the ACG and AGA.<br><br>DESIGN: We constructed a decision-analytic computer simulation using inputs from the published literature to compare the standard approach using tapered vancomycin to FMT for RCDI from the third-party payer perspective. Our effectiveness measure was quality-adjusted life years (QALYs). Because simulated patients were followed for 90 days, discounting was not necessary. One-way and probabilistic sensitivity analyses were performed.<br><br>RESULTS: Base-case analysis showed that FMT was less costly ($1,669 vs $3,788) and more effective (0.242 QALYs vs 0.235 QALYs) than vancomycin for RCDI. One-way sensitivity analyses showed that FMT was the dominant strategy (both less expensive and more effective) if cure rates for FMT and vancomycin were &#x2265;70% and <91%, respectively, and if the cost of FMT was <$3,206. Probabilistic sensitivity analysis, varying all parameters simultaneously, showed that FMT was the dominant strategy over 10, 000 second-order Monte Carlo simulations.<br><br>CONCLUSIONS: Our results suggest that FMT may be a cost-saving intervention in managing RCDI. Implementation of FMT for RCDI may help decrease the economic burden to the healthcare system.}, }
@article {pmid25774048, year = {2015}, author = {Otter, JA}, title = {What's trending in the infection prevention and control literature? From HIS 2012 to HIS 2014, and beyond.}, journal = {The Journal of hospital infection}, volume = {89}, number = {4}, pages = {229-236}, pmid = {25774048}, issn = {1532-2939}, mesh = {Communicable Diseases/*epidemiology/*transmission ; Global Health ; Humans ; Infection Control/*methods/*trends ; Internet/statistics &amp; numerical data ; }, abstract = {This is an informal review of some of the trends in the infection prevention and control literature since the last Healthcare Infection Society (HIS) conference in late 2012. Google Trends was used to investigate how the volume of interest in various infection control topics had changed over time. Ebola trumped all the others in Google searches, reflecting a surge of publications in the literature. Aside from Ebola, other trends in the infection prevention and control literature covered in this article include Middle East Respiratory Syndrome (MERS) coronavirus, universal versus targeted interventions, faecal microbiota transplantation, whole genome sequencing, carbapenem-resistant Enterobacteriaceae, and some aspects of environmental science. The review ends with an attempt to predict some of the trends in the infection prevention and control literature between now and the next HIS conference in 2016.}, }
@article {pmid25773013, year = {2015}, author = {Frudinger, A and Pfeifer, J and Paede, J and Kolovetsiou-Kreiner, V and Marksteiner, R and Halligan, S}, title = {Autologous skeletal-muscle-derived cell injection for anal incontinence due to obstetric trauma: a 5-year follow-up of an initial study of 10 patients.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {17}, number = {9}, pages = {794-801}, doi = {10.1111/codi.12947}, pmid = {25773013}, issn = {1463-1318}, mesh = {Adult ; Aged ; Anal Canal/*injuries/*physiopathology ; Defecation ; Delivery, Obstetric/*adverse effects ; Fecal Incontinence/*etiology/*therapy ; Female ; Follow-Up Studies ; Health Surveys ; Humans ; Injections, Intramuscular ; Manometry ; Middle Aged ; Myoblasts, Skeletal/*transplantation ; Quality of Life ; Severity of Illness Index ; Transplantation, Autologous ; }, abstract = {AIM: Our aim was to determine whether the benefits of autologous skeletal-muscle-derived cell injection to treat obstetric anal incontinence are sustained at 5 years.<br><br>METHOD: An observational study was performed of 10 women suffering from obstetric anal incontinence refractory to non-surgical therapy. Autologous skeletal-muscle-derived cells were injected into the external sphincter defect under ultrasound guidance. Incontinence diaries and quality of life questionnaires were obtained pre-implantation and annually after implantation for 5 years. Anal physiology testing was performed before implantation and at 1, 2 and 5 years after implantation. The end-points included were adverse events, Wexner incontinence scores, incontinence episodes, anal squeeze pressures and quality of life over 5 years. An independent statistician used multilevel linear regression to analyse changes in repeated measures over time. Any skewed distributions were log transformed prior to analysis.<br><br>RESULTS: No procedure-related adverse events occurred and haematological and biochemical parameters were normal during the 5-year period. There were sustained significant improvements in the Wexner incontinence score and reduced frequency of defaecation and number of incontinence episodes (all comparisons P < 0.001). Anal resting and squeeze pressures showed sustained improvement (all P < 0.001) and quality of life improved overall (P < 0.001), including all submeasures studied (P < 0.001).<br><br>CONCLUSION: Autologous skeletal-muscle-derived cells to treat obstetric anal incontinence resulted in sustained improvement in incontinence episodes, physiological measurements of anal function and quality of life at 5 years.}, }
@article {pmid25772685, year = {2015}, author = {Digennaro, R and Pecorella, G and La Manna, S and Alderisio, A and Alderisio, A and De Pascalis, B and Pennisi, D and Santangelo, G and Pezzolla, F and Racalbuto, A and Serra, G and Pulvirenti D'Urso, A and Altomare, DF}, title = {Prospective multicenter observational trial on the safety and efficacy of LEVORAG® Emulgel in the treatment of acute and chronic anal fissure.}, journal = {Techniques in coloproctology}, volume = {19}, number = {5}, pages = {287-292}, pmid = {25772685}, issn = {1128-045X}, mesh = {Acute Disease ; Adult ; Chronic Disease ; Drug Administration Schedule ; Emollients/*therapeutic use ; Female ; Fissure in Ano/*drug therapy ; Gels/therapeutic use ; Humans ; Male ; Middle Aged ; Pain Measurement ; Prospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Anal fissure (AF) is a common cause of anal pain with a tendency not to heal spontaneously because of ischemia of the anoderm caused by sphincter spasm. Lateral internal sphincterotomy, while very effective, can cause fecal incontinence and chemical sphincterotomy by application of cream may have discouraging side effects and/or low efficacy. The aim of this prospective multicenter study was to evaluate the safety and effectiveness of a new medical treatment based on Emulgel cream, with emollient, soothing and protective agents, on AF healing.<br><br>METHODS: Consecutive patients with AF treated in nine coloproctology units during 6 months entered the study on topical treatment with Levorag(&#xae;) Emulgel (THD S.p.A Correggio (RE), Italy). Before treatment, they had a proctologic examination and pain was measured using a visual analog scale. THD Levorag(&#xae;) Emulgel was applied every 12 h for 40 days. Monitoring was scheduled at 10, 20 and 40 days. At time 0 and at the end of treatment, patients underwent anorectal manometry, if possible.<br><br>RESULTS: Two hundred eighty-four AF patients were recruited (171 acute fissures). Complete healing was achieved in 47.9 % of the cases, an improvement in 31.0 % (global efficacy 78.9 %). In patients with acute fissure, the rate of efficacy was 89.4 % (complete healing: 64.3 %, improvement: 25.1 %), in those with chronic fissure the rate of efficacy was 62.8 % (complete healing: 23 %, improvement: 39.8 %), p < 0.001. Pain and resting anal pressure decreased significantly after treatment.<br><br>CONCLUSIONS: Treatment with THD Levorag(&#xae;) Emulgel proved to be effective for the reepithelization of AF and the reduction of pain in the short term in about 80 % of patients.}, }
@article {pmid25772664, year = {2015}, author = {Dinh, A and Bouchand, F and Le Monnier, A}, title = {[Current treatment and epidemiology of Clostridium difficile infections].}, journal = {La Revue de medecine interne}, volume = {36}, number = {9}, pages = {596-602}, doi = {10.1016/j.revmed.2015.02.003}, pmid = {25772664}, issn = {1768-3122}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Child ; *Clostridioides difficile/pathogenicity ; Clostridium Infections/*epidemiology/*therapy ; Colectomy/methods ; Fecal Microbiota Transplantation ; Female ; Humans ; Pregnancy ; Probiotics/therapeutic use ; }, abstract = {During the past 10years, Clostridium difficile infections (CDI) have become a major public health challenge. Their epidemiology has changed with a rise in the number of cases and an increase in severe episodes. Recurrence and failure of conventional treatments have become more common. Furthermore, a spread of CDI has been observed in the general population-involving subjects without the usual risk factors (unexposed to antibiotic treatment, young people, pregnant women, etc.). All these change are partially due to the emergence of the hypervirulent and hyperepidemic clone NAP1/B1/027. New therapeutic strategies (antimicrobial treatment, immunoglobulins, toxin chelation, fecal microbiota transplantation) are now available and conventional treatments (metronidazole and vancomycin) have been reevaluated with new recommendations. Recent studies show a better efficacy of vancomycin compared to metronidazole for severe episodes. Fidaxomicin is a novel antibiotic drug with interesting features, including an efficacy not inferior to vancomycin and a lower risk of recurrence. Finally, for multi-recurrent forms, fecal microbiota transplantation seems to be the best option. We present the available data in this review.}, }
@article {pmid25770145, year = {2015}, author = {Lichtenstein, L and Serhan, N and Espinosa-Delgado, S and Fabre, A and Annema, W and Tietge, UJ and Robaye, B and Boeynaems, JM and Laffargue, M and Perret, B and Martinez, LO}, title = {Increased atherosclerosis in P2Y13/apolipoprotein E double-knockout mice: contribution of P2Y13 to reverse cholesterol transport.}, journal = {Cardiovascular research}, volume = {106}, number = {2}, pages = {314-323}, doi = {10.1093/cvr/cvv109}, pmid = {25770145}, issn = {1755-3245}, mesh = {ATP-Binding Cassette Transporters/genetics/metabolism ; Animals ; Apolipoproteins E/deficiency/*metabolism ; Atherosclerosis/genetics/*metabolism ; Biological Transport/genetics ; Disease Models, Animal ; Lipoproteins, HDL/metabolism ; Liver/metabolism ; Macrophages/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Purinergic P2/deficiency/*metabolism ; }, abstract = {AIMS: High-density lipoproteins (HDLs) protect against atherosclerosis mainly due to their function in hepatobiliary reverse cholesterol transport (RCT). This is a process whereby excess cholesterol from peripheral tissues is transported by HDL particles to the liver for further metabolism and biliary excretion. Hepatic uptake of HDL holoparticles involves the P2Y13 receptor, independently of the selective cholesteryl ester uptake mediated by scavenger receptor class B, type I (SR-BI). Accordingly, P2Y13-deficient mice (P2Y13 (-/-)) have impaired RCT. This study assessed whether P2Y13 deficiency would affect atherosclerotic development.<br><br>METHODS AND RESULTS: P2Y13 (-/-) mice were crossbred with atherosclerosis-prone apoE(-/-) mice. When 15 weeks old, P2Y13 (-/-)/apoE(-/-) mice had more aortic sinus lesions than apoE(-/-) mice. Bone marrow transplantation showed that the absence of the P2Y13 receptor in blood cells did not lead to significantly greater atherosclerotic plaque size formation compared with control apoE(-/-) reconstituted animals. Conversely, the absence of the P2Y13 receptor, except in blood cells, resulted in lesion sizes similar to that in P2Y13 (-/-)/apoE(-/-) reconstituted mice, pointing to a role for non-haematopoietic-derived P2Y13. Unexpectedly, P2Y13 (-/-)/apoE(-/-) mice displayed a lower HDL-cholesterol level than apoE(-/-) mice, which might be due to greater SR-BI expression in the liver. However, P2Y13 deficiency in apoE(-/-) mice was translated into reduced biliary and faecal sterol excretion and impaired RCT from macrophage to faeces, suggesting that an alteration in hepatobiliary RCT could be solely responsible for the greater atherosclerosis observed.<br><br>CONCLUSION: The P2Y13 receptor protects against atherosclerosis, primarily through its role in hepatobiliary RCT.}, }
@article {pmid25769913, year = {2015}, author = {Lane, JP and Stewart, CJ and Cummings, SP and Gennery, AR}, title = {Gut microbiome variations during hematopoietic stem cell transplant in severe combined immunodeficiency.}, journal = {The Journal of allergy and clinical immunology}, volume = {135}, number = {6}, pages = {1654-1656}, doi = {10.1016/j.jaci.2015.01.024}, pmid = {25769913}, issn = {1097-6825}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antifungal Agents/therapeutic use ; Antiviral Agents/therapeutic use ; Bacterial Infections/drug therapy/immunology/microbiology ; Dysbiosis/immunology/*microbiology ; Feces/microbiology ; Female ; Gastrointestinal Tract/immunology/*microbiology/virology ; Graft vs Host Disease/immunology/*microbiology/prevention &amp; control/virology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Infant, Newborn ; Longitudinal Studies ; Male ; Microbiota/*immunology ; Mycoses/drug therapy/immunology/microbiology ; Myeloablative Agonists/therapeutic use ; Pilot Projects ; Severe Combined Immunodeficiency/immunology/*microbiology/therapy/virology ; Transplantation Conditioning ; Virus Diseases/drug therapy/immunology/virology ; }, }
@article {pmid25769877, year = {2015}, author = {García-Mazcorro, JF and Garza-González, E and Marroquín-Cardona, AG and Tamayo, JL}, title = {[Characterization, influence and manipulation of the gastrointestinal microbiota in health and disease].}, journal = {Gastroenterologia y hepatologia}, volume = {38}, number = {7}, pages = {445-466}, doi = {10.1016/j.gastrohep.2015.01.004}, pmid = {25769877}, issn = {0210-5705}, mesh = {Bacterial Typing Techniques ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/physiology ; Health Promotion ; Homeostasis ; Humans ; Infections/microbiology ; Inflammation/microbiology ; Intestinal Diseases, Parasitic/microbiology ; Microbiological Techniques ; Models, Biological ; Overweight/microbiology ; Prebiotics ; Probiotics ; Silicates/therapeutic use ; }, abstract = {The gastrointestinal tract harbors trillions of microorganisms that are indispensable for health. The gastrointestinal microbiota can be studied using culture and molecular methods. The applications of massive sequencing are constantly increasing, due to their high yield, increasingly accessible costs, and the availability of free software for data analysis. The present article provides a detailed review of a large number of studies on the gastrointestinal microbiota and its influence on human health; particular emphasis is placed on the evidence suggesting a relationship between the gastrointestinal microbial ecosystem and diverse physiological and immune/inflammatory processes. Discussion of the articles analyzed combines a medical approach and current concepts of microbial molecular ecology. The present revision aims to be useful to those interested in the gastrointestinal microbiota and its possible alteration to maintain, re-establish and enhance health in the human host.}, }
@article {pmid25769665, year = {2015}, author = {Richardson, C and Kim, P and Lee, C and Bersenas, A and Weese, JS}, title = {Comparison of Clostridium difficile isolates from individuals with recurrent and single episode of infection.}, journal = {Anaerobe}, volume = {33}, number = {}, pages = {105-108}, doi = {10.1016/j.anaerobe.2015.03.003}, pmid = {25769665}, issn = {1095-8274}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/pharmacology ; Clostridioides difficile/classification/drug effects/genetics/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/diagnosis/*microbiology ; Feces/microbiology ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Recurrence ; Ribotyping ; Young Adult ; }, abstract = {PURPOSE: Recurrent Clostridium difficile infection (CDI) is an increasing problem, yet reasons for this are poorly understood. Attention has been paid to the role of strain, with conflicting association of ribotype 027 and recurrences.<br><br>METHODS: Stool samples and medical records data were collected from 60 patients: 27 with recurrent CDI and 33 with single episode CDI. C. difficile was isolated and ribotyped, and minimum inhibitory concentrations of metronidazole and vancomycin were determined by Etest.<br><br>RESULTS: Twenty-seven ribotypes were identified, but only four (027, 014 and two internally designated strains) were found in more than one patient. Ribotype 027 predominated and was significantly over-represented in the recurrent CDI group (70%) versus the single episode CDI group (30%) (P&#xa0;=&#xa0;0.004). Female gender and the presence of ribotype 027 were significantly associated with recurrent CDI in the multivariable model. Metronidazole MICs for recurrent isolates were significantly higher compared to single episode isolates (P&#xa0;&#x2264;&#xa0;0.024). A general linear model indicated that the difference in MIC was associated with ribotype 027 (P&#xa0;=&#xa0;0.0023), not whether the isolate was from recurrent or single episode disease (P&#xa0;=&#xa0;0.25).<br><br>CONCLUSIONS: Ribotype 027 was associated with recurrent disease. While there was no difference in the prevalence of metronidazole resistance, isolates from recurrent CDI patients had significantly higher metronidazole MICs, because of higher MICs in ribotype 027. This study provides further support to the clinical importance of ribotype 027 and raises questions about the potential impact of decreased metronidazole susceptibility on the pathophysiology of recurrent CDI.}, }
@article {pmid25765997, year = {2015}, author = {Horesh, N and Zbar, AP and Nevler, A and Haim, N and Gutman, M and Zmora, O}, title = {Early experience with laparoscopic lavage in acute complicated diverticulitis.}, journal = {Digestive surgery}, volume = {32}, number = {2}, pages = {108-111}, doi = {10.1159/000375539}, pmid = {25765997}, issn = {1421-9883}, mesh = {Acute Disease ; Adult ; Aged ; Combined Modality Therapy ; Diverticulitis, Colonic/complications/*surgery ; Drainage/*methods ; Female ; Follow-Up Studies ; Humans ; *Laparoscopy ; Male ; Middle Aged ; Peritoneal Lavage/*methods ; Peritonitis/etiology/*surgery ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Contemporary surgical management of complicated diverticulitis is controversial. Traditionally, the gold standard has been resection and colostomy, but recently peritoneal lavage and drainage without resection in cases of purulent peritonitis have been suggested. This study aims to review our initial experience with laparoscopic peritoneal lavage for complicated diverticulitis.<br><br>METHODS: Retrospective review of all patients who underwent emergent peritoneal lavage and drainage for acute complicated diverticulitis.<br><br>RESULTS: Five-hundred-thirty-eight patients admitted for acute diverticulitis between 2007 and 2012 were recorded in the database. Thirty seven underwent emergent surgery of which 10 had peritoneal lavage and drainage without colonic resection for complicated diverticulitis causing peritonitis. Peritoneal lavage and drainage resulted in the resolution of acute symptoms in all cases. In long-term follow-up, 3 (30%) patients required elective resection owing to symptomatic disease, two of these due to recurrent diverticulitis, and one owing to complicated fistula following the procedure.<br><br>CONCLUSION: Peritoneal lavage is a feasible option for complicated diverticulitis with purulent non-fecal peritonitis, but a significant portion of the patients may require elective resection. Comparative studies with emergent resection are needed to determine the role of peritoneal lavage in complicated diverticulitis.}, }
@article {pmid25760275, year = {2015}, author = {Jarrad, AM and Karoli, T and Blaskovich, MA and Lyras, D and Cooper, MA}, title = {Clostridium difficile drug pipeline: challenges in discovery and development of new agents.}, journal = {Journal of medicinal chemistry}, volume = {58}, number = {13}, pages = {5164-5185}, pmid = {25760275}, issn = {1520-4804}, support = {/WT_/Wellcome Trust/United Kingdom ; 094977/Z/10/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*drug effects ; *Drug Discovery ; Enterocolitis, Pseudomembranous/*drug therapy/microbiology ; Humans ; }, abstract = {In the past decade Clostridium difficile has become a bacterial pathogen of global significance. Epidemic strains have spread throughout hospitals, while community acquired infections and other sources ensure a constant inoculation of spores into hospitals. In response to the increasing medical burden, a new C. difficile antibiotic, fidaxomicin, was approved in 2011 for the treatment of C. difficile-associated diarrhea. Rudimentary fecal transplants are also being trialed as effective treatments. Despite these advances, therapies that are more effective against C. difficile spores and less damaging to the resident gastrointestinal microbiome and that reduce recurrent disease are still desperately needed. However, bringing a new treatment for C. difficile infection to market involves particular challenges. This review covers the current drug discovery pipeline, including both small molecule and biologic therapies, and highlights the challenges associated with in vitro and in vivo models of C. difficile infection for drug screening and lead optimization.}, }
@article {pmid25753070, year = {2015}, author = {Lankelma, JM and Nieuwdorp, M and de Vos, WM and Wiersinga, WJ}, title = {The gut microbiota in internal medicine: implications for health and disease.}, journal = {The Netherlands journal of medicine}, volume = {73}, number = {2}, pages = {61-68}, pmid = {25753070}, issn = {1872-9061}, mesh = {Anti-Bacterial Agents/therapeutic use ; Gastrointestinal Diseases/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Internal Medicine ; }, abstract = {The human gut microbiota may be viewed as an organ, executing numerous functions in metabolism, development of the immune system and host defence against pathogens. It may therefore be involved in the development of a range of diseases such as gastrointestinal infections, inflammatory bowel disease, allergy and diabetes mellitus. Reversely, certain therapies that are often used, such as antibiotics and chemotherapy, may negatively affect the composition and function of the gut microbiota and thereby the wellbeing of patients. As the microbiota research field is currently moving from association studies to intervention studies and even clinical trials, implementation of this new knowledge into clinical practice is coming near. Several therapeutic interventions that target the gut microbiota are being evaluated, ranging from supplementation of food components to transplantation of faecal microbiota. In this review we provide an overview of current literature on the gut microbiota in both a healthy state and a range of diseases that are relevant for internal medicine. In anticipation of gut microbiota-targeted therapies, it is important to realise the key function of the gut microbiota in physiological processes and the collateral damage that may be caused when disrupting this ecosystem within us.}, }
@article {pmid25749935, year = {2015}, author = {Villanueva-Millán, MJ and Pérez-Matute, P and Oteo, JA}, title = {Gut microbiota: a key player in health and disease. A review focused on obesity.}, journal = {Journal of physiology and biochemistry}, volume = {71}, number = {3}, pages = {509-525}, pmid = {25749935}, issn = {1877-8755}, mesh = {Animals ; Bacterial Translocation ; Fatty Acids/physiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; Lipid Metabolism ; Microbiota ; Obesity/immunology/microbiology ; Signal Transduction ; }, abstract = {Gut microbiota, its evolutive dynamics and influence on host through its protective, trophic and metabolic actions, has a key role in health and opens unique opportunities for the identification of new markers of the physiopathological state of each individual. Alterations in gut microbiota composition have been associated with plenty disorders. Of interest, the vast number of studies demonstrates the role of microbiota in obesity, a serious public health problem that has reached epidemic proportions in many developed and middle-income countries. The economic and health costs of this condition and its comorbidities such as fatty liver, insulin resistance/diabetes, or cardiovascular events are considerable. Therefore, every strategy designed to reduce obesity would imply important savings. Targeting microbiota, in order to restore/modulate the microbiota composition with antibiotics, probiotics, prebiotics, or even fecal transplants, is considered as a promising strategy for the development of new solutions for the treatment of obesity. However, there is still lot to do in this field in order to identify the exact composition of microbiota in "health" and the specific mechanisms that regulate the host-microbiotal crosstalk. In addition, it is important to note that changes not only in the gut microbiota profile (abundance) but also in its metabolism and functions need to be taken into account in the context of contribution in the physiopathology of obesity and related disorders.}, }
@article {pmid25747146, year = {2015}, author = {Bourlioux, P and , }, title = {Faecal microbiota transplantation: Key points to consider.}, journal = {Annales pharmaceutiques francaises}, volume = {73}, number = {3}, pages = {163-168}, doi = {10.1016/j.pharma.2015.02.001}, pmid = {25747146}, issn = {0003-4509}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous/therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; *Microbiota ; Recurrence ; }, abstract = {Faecal microbiota transplantation (FMT) from a healthy donor has become the gold standard treatment for patients suffering from recurrent Clostridium difficile infection where antibiotic treatment (with vancomycin, metronidazole or fidaxomicin) has failed. FMT eradicates C. difficile and helps restore the recipient's intestinal flora, but its mechanism of action remains unclear. Since FMT's complex and highly variable composition cannot be easily characterized - nor its quality routinely assessed - FMT as a sui generis biologic drug cannot conform to existing standards for preparation. Clearly, donors must be carefully selected and the raw material prepared under close microbiological control, but FMT should also conform to manufacturing and laboratory practice standards for which international consensus can only be achieved with further experience. The objective should be to engage biomedical research to develop protocols that help elucidate the mechanism of action of FMT and support the production of safe and efficacious products.}, }
@article {pmid25743672, year = {2015}, author = {Konturek, PC and Hess, T}, title = {[Stool transplantation - gut bacteria as a novel therapeutic option].}, journal = {MMW Fortschritte der Medizin}, volume = {157}, number = {3}, pages = {61-63}, doi = {10.1007/s15006-015-2703-4}, pmid = {25743672}, issn = {1438-3276}, mesh = {Enterocolitis, Necrotizing/microbiology/*therapy ; Feces/*microbiology ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Intestines/*microbiology ; Microbiota/*physiology ; Randomized Controlled Trials as Topic ; Transplantation, Homologous/*methods ; }, }
@article {pmid25742243, year = {2015}, author = {Srinivasan, A and Klepper, C and Sunkara, A and Kang, G and Carr, J and Gu, Z and Leung, W and Hayden, RT}, title = {Impact of adenoviral stool load on adenoviremia in pediatric hematopoietic stem cell transplant recipients.}, journal = {The Pediatric infectious disease journal}, volume = {34}, number = {6}, pages = {562-565}, pmid = {25742243}, issn = {1532-0987}, support = {P30 CA021765/CA/NCI NIH HHS/United States ; R25 CA023944/CA/NCI NIH HHS/United States ; 5R25CA02394/CA/NCI NIH HHS/United States ; P30 CA 21765/CA/NCI NIH HHS/United States ; }, mesh = {Adenoviridae/*isolation &amp; purification ; Adenoviridae Infections/*virology ; Adolescent ; Blood/*virology ; Child ; Child, Preschool ; Feces/*virology ; Female ; *Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Male ; Mamastrovirus/isolation &amp; purification ; Norovirus/isolation &amp; purification ; Retrospective Studies ; Sapovirus/isolation &amp; purification ; *Viral Load ; Viremia/*virology ; Young Adult ; }, abstract = {BACKGROUND: Adenoviremia adversely affects prognosis in the post-hematopoietic stem cell transplant setting.<br><br>METHODS: We sought to determine retrospectively the cutoff load of adenovirus in the stool as a predictor of adenoviremia, in children who underwent an allogeneic hematopoietic stem cell transplant. The prevalence of sapovirus, norovirus and astrovirus in the stool was also studied.<br><br>RESULTS: The study cohort consisted of 117 patients, of which 71 (60%) had diarrhea. Adenovirus was detected in the stool in 39 of 71 (55%) patients. Age &#x2264;10 years (P = 0.05; odds ratio: 2.57; 95% confidence interval: 0.98-6.75) and male sex (P = 0.04; odds ratio: 2.67; 95% confidence interval: 1.02-6.99) increased risk for detection of adenovirus in stool on univariate analysis. Coinfections with enteric pathogens were infrequent. Viral load >10 copies/g stool predicted adenoviremia with a sensitivity and specificity of 82%. Sapovirus, norovirus and astrovirus were detected in 3, 4 and 1 patient, respectively.<br><br>CONCLUSIONS: Quantitative detection of adenovirus in stool may have implications for preemptive therapy. Testing for other enteric viruses may have implications for infection control.}, }
@article {pmid25735732, year = {2015}, author = {Yusta, B and Baggio, LL and Koehler, J and Holland, D and Cao, X and Pinnell, LJ and Johnson-Henry, KC and Yeung, W and Surette, MG and Bang, KW and Sherman, PM and Drucker, DJ}, title = {GLP-1R Agonists Modulate Enteric Immune Responses Through the Intestinal Intraepithelial Lymphocyte GLP-1R.}, journal = {Diabetes}, volume = {64}, number = {7}, pages = {2537-2549}, doi = {10.2337/db14-1577}, pmid = {25735732}, issn = {1939-327X}, support = {123391//Canadian Institutes of Health Research/Canada ; IOP-92890//Canadian Institutes of Health Research/Canada ; MOP-89894//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Cytokines/analysis ; Exenatide ; Female ; Glucagon-Like Peptide 1/metabolism/pharmacology ; Glucagon-Like Peptide-1 Receptor ; Immunity, Innate ; Intestinal Mucosa/*immunology ; Lymphocytes/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Peptides/pharmacology ; Receptors, Glucagon/*agonists/*physiology ; Signal Transduction ; Venoms/pharmacology ; }, abstract = {Obesity and diabetes are characterized by increased inflammation reflecting disordered control of innate immunity. We reveal a local intestinal intraepithelial lymphocyte (IEL)-GLP-1 receptor (GLP-1R) signaling network that controls mucosal immune responses. Glp1r expression was enriched in intestinal IEL preparations and copurified with markers of Tαβ and Tγδ IELs, the two main subsets of intestinal IELs. Exendin-4 increased cAMP accumulation in purified IELs and reduced the production of cytokines from activated IELs but not from splenocytes ex vivo. These actions were mimicked by forskolin, absent in IELs from Glp1r(-/-) mice, and attenuated by the GLP-1R agonist exendin (9-39) consistent with a GLP-1R-dependent mechanism of action. Furthermore, Glp1r(-/-) mice exhibited dysregulated intestinal gene expression, an abnormal representation of microbial species in feces, and enhanced sensitivity to intestinal injury following administration of dextran sodium sulfate. Bone marrow transplantation using wild-type C57BL/6 donors normalized expression of multiple genes regulating immune function and epithelial integrity in Glp1r(-/-) recipient mice, whereas acute exendin-4 administration robustly induced the expression of genes encoding cytokines and chemokines in normal and injured intestine. Taken together, these findings define a local enteroendocrine-IEL axis linking energy availability, host microbial responses, and mucosal integrity to the control of innate immunity.}, }
@article {pmid25731162, year = {2015}, author = {Chassaing, B and Koren, O and Goodrich, JK and Poole, AC and Srinivasan, S and Ley, RE and Gewirtz, AT}, title = {Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.}, journal = {Nature}, volume = {519}, number = {7541}, pages = {92-96}, pmid = {25731162}, issn = {1476-4687}, support = {R01 DK099071/DK/NIDDK NIH HHS/United States ; DK083890/DK/NIDDK NIH HHS/United States ; R01 DK083890/DK/NIDDK NIH HHS/United States ; DK099071/DK/NIDDK NIH HHS/United States ; U24 DK097153/DK/NIDDK NIH HHS/United States ; }, mesh = {Adiposity/drug effects ; Animals ; Carboxymethylcellulose Sodium/administration &amp; dosage/adverse effects ; Colitis/*chemically induced/*microbiology/pathology ; Diet/*adverse effects ; Emulsifying Agents/administration &amp; dosage/*adverse effects ; Feces/microbiology ; Female ; Gastrointestinal Tract/*drug effects/*microbiology/pathology ; Germ-Free Life ; Inflammation/chemically induced/microbiology/pathology ; Intestinal Mucosa/drug effects/microbiology/pathology ; Male ; Metabolic Syndrome/*chemically induced/*microbiology/pathology ; Mice ; Microbiota/drug effects ; Obesity/chemically induced/microbiology/pathology ; Polysorbates/administration &amp; dosage/adverse effects ; }, abstract = {The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multi-layered mucus structures that cover the intestinal surface, thereby allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro, might be promoting the increase in inflammatory bowel disease observed since the mid-twentieth century. Here we report that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in wild-type hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition and increased pro-inflammatory potential. Use of germ-free mice and faecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.}, }
@article {pmid25728826, year = {2015}, author = {Jain, A and Humar, A and Lien, D and Weinkauf, J and Kumar, D}, title = {Strategies for safe living among lung transplant recipients: a single-center survey.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {17}, number = {2}, pages = {185-191}, doi = {10.1111/tid.12354}, pmid = {25728826}, issn = {1399-3062}, mesh = {Adolescent ; Adult ; Aged ; Drinking Water ; Female ; Food Safety ; Gardening/statistics &amp; numerical data ; Graft Rejection/*prevention &amp; control ; *Hand Disinfection ; *Health Behavior ; Humans ; *Immunocompromised Host ; Immunosuppressive Agents/*therapeutic use ; *Lung Transplantation ; Male ; Masks/*statistics &amp; numerical data ; Middle Aged ; Occupational Exposure/statistics &amp; numerical data ; *Pets ; Surveys and Questionnaires ; Transplant Recipients ; Travel/statistics &amp; numerical data ; Young Adult ; }, abstract = {BACKGROUND: Lung transplant (LT) recipients are at high risk for infection owing to lifelong immunosuppression and direct communication of the graft with the environment. Guidelines have been established for safe-living strategies after transplantation. We conducted a survey of LT patients to determine compliance with these strategies.<br><br>METHODS: Adult LT outpatients completed a survey consisting of questions on a 5-point Likert scale with the following categories: hand washing, gardening, respiratory infections, food and water safety, animal contact, travel, and occupation.<br><br>RESULTS: A total of 194 LT recipients completed the survey (age 54.4&#xa0;&#xb1;&#xa0;13.3&#xa0;years; time post transplant 4.76&#xa0;&#xb1;&#xa0;3.5&#xa0;years). Regular hand washing was practiced usually or always by 87.6%. Of those who worked with soil/gardened, 70/99 (70.7%) never wore a mask and 15.7% never wore gloves. Pet ownership was common (52%), but most patients used specific precautions during handling. Over one-third of patients continued employment after transplant but, of these, 56% had modified their occupation often because of perceived infectious risks. Most patients were fully compliant with influenza vaccination (92.3%). Patients <40&#xa0;years of age were less likely to wear long-sleeved clothing in mosquito season (P&#xa0;=&#xa0;0.002), more likely to handle pet feces (P&#xa0;=&#xa0;0.005), and less likely to wear a mask with sick contacts (P&#xa0;=&#xa0;0.021).<br><br>CONCLUSIONS: We provide important insight into safe-living practices following lung transplantation and identify specific areas and subgroups of patients that could be targeted for enhanced education, with potential significant clinical benefit.}, }
@article {pmid25728808, year = {2015}, author = {Cammarota, G and Masucci, L and Ianiro, G and Bibbò, S and Dinoi, G and Costamagna, G and Sanguinetti, M and Gasbarrini, A}, title = {Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {41}, number = {9}, pages = {835-843}, doi = {10.1111/apt.13144}, pmid = {25728808}, issn = {1365-2036}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/drug therapy/therapy ; Colonoscopy/*methods ; Diarrhea/drug therapy ; Enterocolitis, Pseudomembranous/drug therapy/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Microbiota ; Middle Aged ; Treatment Outcome ; Vancomycin/*therapeutic use ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) from healthy donors is considered an effective treatment against recurrent Clostridium difficile infection.<br><br>AIM: To study the effect of FMT via colonoscopy in patients with recurrent C. difficile infection compared to the standard vancomycin regimen.<br><br>METHODS: In an open-label, randomised clinical trial, we assigned subjects with recurrent C. difficile infection to receive: FMT, short regimen of vancomycin (125&#xa0;mg four times a day for 3&#xa0;days), followed by one or more infusions of faeces via colonoscopy; or vancomycin, vancomycin 125&#xa0;mg four times daily for 10&#xa0;days, followed by 125-500&#xa0;mg/day every 2-3&#xa0;days for at least 3&#xa0;weeks. The latter treatment did not include performing colonoscopy. The primary end point was the resolution of diarrhoea related to C. difficile infection 10&#xa0;weeks after the end of treatments.<br><br>RESULTS: The study was stopped after a 1-year interim analysis. Eighteen of the 20 patients (90%) treated by FMT exhibited resolution of C. difficile-associated diarrhoea. In FMT, five of the seven patients with pseudomembranous colitis reported a resolution of diarrhoea. Resolution of C. difficile infection occurred in 5 of the 19 (26%) patients in vancomycin (P&#xa0;<&#xa0;0.0001). No significant adverse events were observed in either of the study groups.<br><br>CONCLUSIONS: Faecal microbiota transplantation using colonoscopy to infuse faeces was significantly more effective than vancomycin regimen for the treatment of recurrent C. difficile infection. The delivery of donor faeces via colonoscopy has the potential to optimise the treatment strategy in patients with pseudomembranous colitis.}, }
@article {pmid25728703, year = {2015}, author = {Grąt, M and Hołówko, W and Wronka, KM and Grąt, K and Lewandowski, Z and Kosińska, I and Krasnodębski, M and Wasilewicz, M and Gałęcka, M and Szachta, P and Zborowska, H and Patkowski, W and Krawczyk, M}, title = {The relevance of intestinal dysbiosis in liver transplant candidates.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {17}, number = {2}, pages = {174-184}, doi = {10.1111/tid.12352}, pmid = {25728703}, issn = {1399-3062}, mesh = {Adult ; Aged ; Bifidobacterium/isolation &amp; purification ; Bilirubin/blood ; Cohort Studies ; Creatinine/blood ; Dysbiosis/blood/*microbiology ; End Stage Liver Disease/blood/*microbiology/surgery ; Enterococcus/isolation &amp; purification ; Escherichia coli/isolation &amp; purification ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; International Normalized Ratio ; Lactobacillus/isolation &amp; purification ; Linear Models ; Liver Cirrhosis/blood/*microbiology/surgery ; *Liver Transplantation ; Male ; Middle Aged ; Prospective Studies ; Severity of Illness Index ; Yeasts/isolation &amp; purification ; Young Adult ; }, abstract = {BACKGROUND: The gut microbial ecosystem plays an important role in the pathogenesis of liver diseases. However, the association of microbial community structure with the severity of liver dysfunction is not completely understood.<br><br>METHODS: Fecal microflora was assessed in 40 patients with liver cirrhosis listed for primary liver transplantation (LT). Independent associations between fecal microbial counts and serum bilirubin, serum creatinine, international normalized ratio (INR), and the Model for End-stage Liver Disease (MELD) score were established in multiple linear regression models.<br><br>RESULTS: Bifidobacterium (standardized regression coefficient [s&#x3b2;]&#xa0;=&#xa0;-0.549; P&#xa0;<&#xa0;0.001), Enterococcus (s&#x3b2;&#xa0;=&#xa0;0.369; P&#xa0;=&#xa0;0.004), and yeast (s&#x3b2;&#xa0;=&#xa0;0.315; P&#xa0;=&#xa0;0.018) numbers were independently associated with serum bilirubin, while Escherichia coli counts (s&#x3b2;&#xa0;=&#xa0;0.318; P&#xa0;=&#xa0;0.046) correlated with INR, and Bifidobacterium counts (s&#x3b2;&#xa0;=&#xa0;0.410; P&#xa0;=&#xa0;0.009) with serum creatinine. Only Bifidobacterium (s&#x3b2;&#xa0;=&#xa0;-0.468; P&#xa0;=&#xa0;0.003) and Enterococcus (s&#x3b2;&#xa0;=&#xa0;0.331; P&#xa0;=&#xa0;0.029) counts were independent predictors of the MELD score. Bifidobacterium/Enterococcus ratio, proposed as a measure of pre-LT gut dysbiosis, was significantly related to the MELD score following the adjustment for the absolute Bifidobacterium (s&#x3b2;&#xa0;=&#xa0;-0.333; P&#xa0;=&#xa0;0.029) and Enterococcus (s&#x3b2;&#xa0;=&#xa0;-0.966; P&#xa0;=&#xa0;0.003) numbers. This pre-transplant dysbiosis ratio (PTDR) was significantly correlated with Enterococcus (R&#xa0;=&#xa0;-0.897; P&#xa0;<&#xa0;0.001) but not with Bifidobacterium (R&#xa0;=&#xa0;0.098; P&#xa0;=&#xa0;0.546) counts. Among the other components of gut microflora, only hydrogen peroxide (H2 O2)-producing Lactobacillus strains significantly influenced Enterococcus counts (s&#x3b2;&#xa0;=&#xa0;0.349; P&#xa0;=&#xa0;0.028) and PTDR (s&#x3b2;&#xa0;=&#xa0;-0.318; P&#xa0;=&#xa0;0.046).<br><br>CONCLUSION: While the abundance of both Bifidobacterium and Enterococcus is related to liver dysfunction, the size of the Enterococcus population seems to be the most important determinant of pre-LT gut dysbiosis in cirrhotic patients. The H2 O2 -producing Lactobacillus strains potentially ameliorate this dysbiotic state.}, }
@article {pmid25721003, year = {2015}, author = {Gweon, TG and Lee, KJ and Kang, DH and Park, SS and Kim, KH and Seong, HJ and Ban, TH and Moon, SJ and Kim, JS and Kim, SW}, title = {A case of toxic megacolon caused by clostridium difficile infection and treated with fecal microbiota transplantation.}, journal = {Gut and liver}, volume = {9}, number = {2}, pages = {247-250}, pmid = {25721003}, issn = {2005-1212}, mesh = {Aged ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*complications ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Humans ; Male ; Megacolon, Toxic/*microbiology/*therapy ; }, abstract = {Clostridium difficile infection. The mortality rate of fulminant C. difficile infection is reported to be as high as 50%. Fecal microbiota transplantation is a highly effective treatment in patients with recurrent or refractory C. difficile infection. However, there are few published articles on the use of such transplantation for fulminant C. difficile infection. Here, we report on a patient with toxic megacolon complicated by C. difficile infection who was treated successfully with fecal mi-crobiota transplantation. (Gut Liver, 2015;9:247-250).}, }
@article {pmid25716681, year = {2015}, author = {Poutahidis, T and Varian, BJ and Levkovich, T and Lakritz, JR and Mirabal, S and Kwok, C and Ibrahim, YM and Kearney, SM and Chatzigiagkos, A and Alm, EJ and Erdman, SE}, title = {Dietary microbes modulate transgenerational cancer risk.}, journal = {Cancer research}, volume = {75}, number = {7}, pages = {1197-1204}, pmid = {25716681}, issn = {1538-7445}, support = {U01 CA164337/CA/NCI NIH HHS/United States ; U01CA164337/CA/NCI NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; R01 CA108854/CA/NCI NIH HHS/United States ; R01CA108854/CA/NCI NIH HHS/United States ; P30-ES002109/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Animals, Outbred Strains ; Diet, Western/adverse effects ; Feces/microbiology ; Female ; Gastrointestinal Tract/microbiology ; Male ; Mice ; *Microbiota ; Neoplasms/*microbiology ; Obesity/etiology ; Risk ; }, abstract = {Environmental factors are suspected in the increase of obesity and cancer in industrialized countries but are poorly understood. Here, we used animal models to test how future generations may be affected by Westernized diets. We discover long-term consequences of grandmothers' in utero dietary exposures, leading to high rates of obesity and frequent cancers of lung and liver in two subsequent generations of mice. Transgenerational effects were transplantable using diet-associated bacteria communities alone. Consequently, feeding of beneficial microbes was sufficient to lower transgenerational risk for cancer and obesity regardless of diet history. Targeting microbes may be a highly effective population-based approach to lower risk for cancer.}, }
@article {pmid25710027, year = {2015}, author = {Damms-Machado, A and Mitra, S and Schollenberger, AE and Kramer, KM and Meile, T and Königsrainer, A and Huson, DH and Bischoff, SC}, title = {Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {806248}, pmid = {25710027}, issn = {2314-6141}, mesh = {Bacteria/*isolation &amp; purification ; *Caloric Restriction ; Combined Modality Therapy ; Female ; *Gastrectomy ; Gastrointestinal Microbiome ; Germany ; Humans ; *Intestinal Absorption ; Middle Aged ; Obesity/*microbiology/physiopathology/*therapy ; Treatment Outcome ; }, abstract = {Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction. Laparoscopic sleeve gastrectomy (LSG), a surgical intervention for obesity, is classified as predominantly restrictive procedure. In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects (n = 5 per group) demonstrating identical weight loss during a follow-up period of six months. For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics. The energy-reabsorbing potential of the gut microbiota decreased following LSG, indicated by the Bacteroidetes/Firmicutes ratio, but increased during diet. Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups. No alteration of faecal butyrate was observed, but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention. LSG resulted in enhanced faecal excretion of nonesterified fatty acids and bile acids. LSG, but not dietetic restriction, improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype. Moreover, LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation. This trial is registered with ClinicalTrials.gov NCT01344525.}, }
@article {pmid25709718, year = {2015}, author = {Shanahan, F}, title = {Separating the microbiome from the hyperbolome.}, journal = {Genome medicine}, volume = {7}, number = {1}, pages = {17}, pmid = {25709718}, issn = {1756-994X}, abstract = {Microbiome-based therapies are moving quickly towards the clinic, with successes including fecal microbial transplants for recurring Clostridium difficile, hints of new antibiotics to come, and possible new microbial biomarkers for common complex diseases. Can the microbiome live up to its hype?}, }
@article {pmid25707891, year = {2015}, author = {Matuchansky, C}, title = {Fecal microbiota transplantation: the case of immunocompromised patients.}, journal = {The American journal of medicine}, volume = {128}, number = {3}, pages = {e21}, doi = {10.1016/j.amjmed.2014.06.020}, pmid = {25707891}, issn = {1555-7162}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; *Microbiota ; }, }
@article {pmid25707687, year = {2015}, author = {Karczewski, J and Swora-Cwynar, E and Rzymski, P and Poniedziałek, B and Adamski, Z}, title = {Selected biologic markers of inflammation and activity of Crohn's disease.}, journal = {Autoimmunity}, volume = {48}, number = {5}, pages = {318-327}, doi = {10.3109/08916934.2015.1016221}, pmid = {25707687}, issn = {1607-842X}, mesh = {Adult ; *Biomarkers ; Crohn Disease/blood/*diagnosis/*metabolism ; Cytokines/blood ; Endoscopy, Gastrointestinal ; Female ; Humans ; Inflammation Mediators/blood ; Male ; Middle Aged ; ROC Curve ; Severity of Illness Index ; Young Adult ; }, abstract = {The study aimed to compare the accuracy of selected biologic markers in assessing the disease activity in patients with Crohn's disease (CD). The analysis included serum IL-2, IL-6, IL-17, TNF-α, IFN-γ, hsCRP, peripheral CD4 + CD25 + FOXP3 + regulatory T cells, as well as fecal calprotectin and lactoferrin. A group of 55 adults with CD was enrolled to the study. Disease activity was assessed using Crohn's Disease Endoscopic Index of Severity (CDEIS), which currently represents the gold standard for the evaluation of endoscopic activity. For clinical activity scoring, the Crohn's Disease Activity Index (CDAI) was used. Concentrations of investigated markers were estimated by means of flow cytometry and enzyme-linked immunosorbent assays, and the results were correlated with both indices. The study demonstrated that both fecal markers, i.e. calprotectin (r = 0.827, p < 0.001) and lactoferrin (r = 0.704, p < 0.001), correlate closely with CDEIS score, and might be used to evaluate the severity of CD in clinical setting. The correlation of those markers with CDAI was also significant, with r = 0.742 for calprotectin (p < 0.001) and r = 0.675 for lactoferrin (p < 0.05). As for the other investigated markers, only hsCRP (r = 0.672, p < 0.001) and IL-17 (r = 0.296, p < 0.005) correlated closely with CDEIS. The correlation of the markers with CDAI was also significant, though weaker, with r = 0.518 for hsCRP (p < 0.001) and r = 0.296 for IL-17 (p < 0.05). The study showed that IL-17, despite its vague role in the pathogenesis of CD, might be a useful marker, comparable with hsCRP, in assessing the activity of the disease.}, }
@article {pmid25705630, year = {2014}, author = {Zatorski, H and Fichna, J}, title = {What is the Future of the Gut Microbiota-Related Treatment? Toward Modulation of Microbiota in Preventive and Therapeutic Medicine.}, journal = {Frontiers in medicine}, volume = {1}, number = {}, pages = {19}, pmid = {25705630}, issn = {2296-858X}, }
@article {pmid25703532, year = {2015}, author = {Di Bella, S and Gouliouris, T and Petrosillo, N}, title = {Fecal microbiota transplantation (FMT) for Clostridium difficile infection: focus on immunocompromised patients.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {21}, number = {4}, pages = {230-237}, doi = {10.1016/j.jiac.2015.01.011}, pmid = {25703532}, issn = {1437-7780}, mesh = {Adult ; Aged ; *Clostridioides difficile ; *Clostridium Infections/epidemiology/therapy ; *Fecal Microbiota Transplantation/adverse effects/statistics &amp; numerical data ; Female ; Humans ; *Immunocompromised Host ; Male ; Middle Aged ; Treatment Outcome ; Young Adult ; }, abstract = {Clostridium difficile infection (CDI) is an emerging problem worldwide associated with significant morbidity, mortality, recurrence rates and healthcare costs. Immunosuppressed patients, including HIV-seropositive individuals, solid organ transplant recipients, patients with malignancies, hematopoietic stem cell transplant recipients, and patients with inflammatory bowel disease are increasingly recognized as being at higher risk of developing CDI where it may be associated with significant complications, recurrence, and mortality. Fecal microbiota transplantation (FMT) has proven to be an effective and safe procedure for the treatment of recurrent or refractory CDI in immunocompetent patients by restoring the gut microbiota and resistance to further recurrences. During the last two years the first data on FMT in immunocompromised patients began to appear in the medical literature. Herein we summarize the use of FMT for the treatment of CDI with a focus on immunocompromised patients.}, }
@article {pmid25691847, year = {2015}, author = {Jang, MO and An, JH and Jung, SI and Park, KH}, title = {Refractory Clostridium difficile Infection Cured With Fecal Microbiota Transplantation in Vancomycin-Resistant Enterococcus Colonized Patient.}, journal = {Intestinal research}, volume = {13}, number = {1}, pages = {80-84}, pmid = {25691847}, issn = {1598-9100}, abstract = {The rates and severity of Clostridium difficile infections, including pseudomembranous colitis, have increased markedly. However, there are few effective treatments for refractory or recurrent C. difficile infections and the outcomes are poor. Fecal microbiota transplantation is becoming increasingly accepted as an effective and safe intervention in patients with recurrent disease, likely due to the restoration of a disrupted microbiome. Cure rates of >90% are being consistently reported from multiple centers. We cured a case of severe refractory C. difficile infection with fecal microbiota transplantation in a patient colonized by vancomycin-resistant enterococcus.}, }
@article {pmid25689657, year = {2015}, author = {Blackburn, LM and Bales, A and Caldwell, M and Cordell, L and Hamilton, S and Kreider, H}, title = {Fecal microbiota transplantation in patients with cancer undergoing treatment.}, journal = {Clinical journal of oncology nursing}, volume = {19}, number = {1}, pages = {111-114}, doi = {10.1188/15.CJON.111-114}, pmid = {25689657}, issn = {1538-067X}, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation/methods ; Humans ; Neoplasms/therapy ; Opportunistic Infections/therapy ; }, abstract = {Fecal microbiota transplantation (FMT) is a technique used to restore the normal body flora to the gut in cases of Clostridium difficile infection (CDI). It involves instillation of the stool of a healthy donor through a nasogastric tube or colonoscopy into the gastrointestinal tract of the patient. More research is needed to determine the parameters of FMT use in patients with cancer.}, }
@article {pmid25688788, year = {2015}, author = {Youngster, I and Hohmann, EL}, title = {Fecal microbiota transplantation for Clostridium difficile infection--reply.}, journal = {JAMA}, volume = {313}, number = {7}, pages = {726}, doi = {10.1001/jama.2014.18619}, pmid = {25688788}, issn = {1538-3598}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; Transplantation/*methods ; }, }
@article {pmid25688787, year = {2015}, author = {Armstrong, MJ and Pathmakanthan, S and Iqbal, TH}, title = {Fecal microbiota transplantation for Clostridium difficile infection.}, journal = {JAMA}, volume = {313}, number = {7}, pages = {725-726}, doi = {10.1001/jama.2014.18617}, pmid = {25688787}, issn = {1538-3598}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; Transplantation/*methods ; }, }
@article {pmid25687205, year = {2015}, author = {Aratari, A and Cammarota, G and Papi, C}, title = {Fecal microbiota transplantation for recurrent C. difficile infection in a patient with chronic refractory ulcerative colitis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {9}, number = {4}, pages = {367}, doi = {10.1093/ecco-jcc/jjv034}, pmid = {25687205}, issn = {1876-4479}, mesh = {Adult ; Chronic Disease ; Clostridioides difficile/*isolation &amp; purification ; Colitis, Ulcerative/*complications/microbiology ; Enterocolitis, Pseudomembranous/complications/*microbiology ; Fecal Microbiota Transplantation/*adverse effects ; Feces/microbiology ; Humans ; Male ; }, }
@article {pmid25686606, year = {2015}, author = {Moon, C and Baldridge, MT and Wallace, MA and D, CA and Burnham,  and Virgin, HW and Stappenbeck, TS}, title = {Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation.}, journal = {Nature}, volume = {521}, number = {7550}, pages = {90-93}, pmid = {25686606}, issn = {1476-4687}, support = {R01 DK097079/DK/NIDDK NIH HHS/United States ; P30DK052574/DK/NIDDK NIH HHS/United States ; R01 DK071619/DK/NIDDK NIH HHS/United States ; P30AR048335/AR/NIAMS NIH HHS/United States ; R01 DK101354/DK/NIDDK NIH HHS/United States ; T32AI007163/AI/NIAID NIH HHS/United States ; T32CA009547/CA/NCI NIH HHS/United States ; T32 CA009547/CA/NCI NIH HHS/United States ; DK7161907/DK/NIDDK NIH HHS/United States ; P30 AR048335/AR/NIAMS NIH HHS/United States ; T32 AI007163/AI/NIAID NIH HHS/United States ; AI08488702/AI/NIAID NIH HHS/United States ; R01 OD011170/OD/NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; }, mesh = {Ampicillin/pharmacology ; Anaerobiosis ; Animals ; Biomarkers/analysis ; Chromosomes, Mammalian/genetics ; Feces/*microbiology ; Female ; Immunoglobulin A/*analysis/*immunology/metabolism ; Immunoglobulin A, Secretory/metabolism ; Male ; Mice ; Microbiota/drug effects/immunology ; Mutation ; *Phenotype ; Reproducibility of Results ; Secretory Component/immunology/metabolism ; }, abstract = {The proliferation of genetically modified mouse models has exposed phenotypic variation between investigators and institutions that has been challenging to control. In many cases, the microbiota is the presumed cause of the variation. Current solutions to account for phenotypic variability include littermate and maternal controls or defined microbial consortia in gnotobiotic mice. In conventionally raised mice, the microbiome is transmitted from the dam. Here we show that microbially driven dichotomous faecal immunoglobulin-A (IgA) levels in wild-type mice within the same facility mimic the effects of chromosomal mutations. We observe in multiple facilities that vertically transmissible bacteria in IgA-low mice dominantly lower faecal IgA levels in IgA-high mice after co-housing or faecal transplantation. In response to injury, IgA-low mice show increased damage that is transferable by faecal transplantation and driven by faecal IgA differences. We find that bacteria from IgA-low mice degrade the secretory component of secretory IgA as well as IgA itself. These data indicate that phenotypic comparisons between mice must take into account the non-chromosomal hereditary variation between different breeders. We propose faecal IgA as one marker of microbial variability and conclude that co-housing and/or faecal transplantation enables analysis of progeny from different dams.}, }
@article {pmid25685657, year = {2015}, author = {Jump, RL and Donskey, CJ}, title = {Clostridium difficile in the Long-Term Care Facility: Prevention and Management.}, journal = {Current geriatrics reports}, volume = {4}, number = {1}, pages = {60-69}, pmid = {25685657}, issn = {2196-7865}, support = {KL2 TR000440/TR/NCATS NIH HHS/United States ; R03 AG040722/AG/NIA NIH HHS/United States ; UL1 TR000439/TR/NCATS NIH HHS/United States ; }, abstract = {Residents of long-term care facilities are at high risk for Clostridium difficile infection due to frequent antibiotic exposure in a population already rendered vulnerable to infection due to advanced age, multiple comorbid conditions and communal living conditions. Moreover, asymptomatic carriage of toxigenic C. difficile and recurrent infections are prevalent in this population. Here, we discuss epidemiology and management of C. difficile infection among residents of long-term care facilities. Also, recognizing that both the population and culture differs significantly from that of hospitals, we also address prevention strategies specific to LTCFs.}, }
@article {pmid25681196, year = {2015}, author = {Gu, YH and Yokoyama, K and Mizuta, K and Tsuchioka, T and Kudo, T and Sasaki, H and Nio, M and Tang, J and Ohkubo, T and Matsui, A}, title = {Stool color card screening for early detection of biliary atresia and long-term native liver survival: a 19-year cohort study in Japan.}, journal = {The Journal of pediatrics}, volume = {166}, number = {4}, pages = {897-902.e1}, doi = {10.1016/j.jpeds.2014.12.063}, pmid = {25681196}, issn = {1097-6833}, mesh = {Biliary Atresia/*diagnosis/mortality/surgery ; *Early Diagnosis ; Feces/*chemistry ; Female ; Follow-Up Studies ; *Forecasting ; Humans ; Infant, Newborn ; Japan/epidemiology ; Kaplan-Meier Estimate ; Male ; Mass Screening/*methods ; Portoenterostomy, Hepatic/methods ; Predictive Value of Tests ; Pregnancy ; Retrospective Studies ; Survival Rate/trends ; }, abstract = {OBJECTIVE: To evaluate the sensitivity and specificity of a stool color card used for a mass screening of biliary atresia conducted over 19 years. In addition, the age at Kasai procedure and the long-term probabilities of native liver survival were investigated.<br><br>STUDY DESIGN: From 1994 to 2011, the stool color card was distributed to all pregnant women in Tochigi Prefecture, Japan. Before or during the postnatal 1-month health checkup, the mothers returned the completed stool color card to the attending pediatrician or obstetrician. All suspected cases of biliary atresia were referred for further examination. Diagnosis was confirmed by laparotomy or operative cholangiography for high-risk cases before the Kasai procedure. Patients with biliary atresia were followed from the date of their Kasai procedure until liver transplantation, death, or October 31, 2013, whichever comes sooner.<br><br>RESULTS: A total of 313,230 live born infants were screened; 34 patients with biliary atresia were diagnosed. The sensitivity and specificity of stool color card screening at the 1-month check-up was 76.5% (95% CI 62.2-90.7) and 99.9% (95% CI 99.9-100.0), respectively. Mean age at the time of Kasai procedure was 59.7 days. According to Kaplan-Meier analysis, the native liver survival probability at 5, 10, and 15 years was 87.6%, 76.9%, and 48.5%, respectively.<br><br>CONCLUSIONS: The sensitivity and specificity of the stool color card have been demonstrated by our 19-year cohort study. We found that the timing of Kasai procedure and long-term native liver survival probabilities were improved, suggesting the beneficial effect of stool color card screening.}, }
@article {pmid25680316, year = {2015}, author = {Rossen, NG and Bart, A and Verhaar, N and van Nood, E and Kootte, R and de Groot, PF and D'Haens, GR and Ponsioen, CY and van Gool, T}, title = {Low prevalence of Blastocystis sp. in active ulcerative colitis patients.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {34}, number = {5}, pages = {1039-1044}, pmid = {25680316}, issn = {1435-4373}, mesh = {Adult ; Blastocystis/*isolation &amp; purification ; Blastocystis Infections/*complications/*epidemiology ; Cohort Studies ; Colitis, Ulcerative/*etiology ; Female ; Humans ; Male ; Prevalence ; Randomized Controlled Trials as Topic ; Young Adult ; }, abstract = {Ulcerative colitis (UC) is thought to originate from a disbalance in the interplay between the gut microbiota and the innate and adaptive immune system. Apart from the bacterial microbiota, there might be other organisms, such as parasites or viruses, that could play a role in the aetiology of UC. The primary objective of this study was to compare the prevalence of Blastocystis sp. in a cohort of patients with active UC and compare that to the prevalence in healthy controls. We studied patients with active UC confirmed by endoscopy included in a randomised prospective trial on the faecal transplantation for UC. A cohort of healthy subjects who served as donors in randomised trials on faecal transplantation were controls. Healthy subjects did not have gastrointestinal symptoms and were extensively screened for infectious diseases by a screenings questionnaire, extensive serologic assessment for viruses and stool analysis. Potential parasitic infections such as Blastocystis were diagnosed with the triple faeces test (TFT). The prevalence of Blastocystis sp. were compared between groups by Chi-square testing. A total of 168 subjects were included, of whom 45 had active UC [median age 39.0 years, interquartile range (IQR) 32.5-49.0, 49 % male] and 123 were healthy subjects (median age 27 years, IQR 22.0-37.0, 54 % male). Blastocystis sp. was present in the faeces of 40/123 (32.5 %) healthy subjects and 6/45 (13.3 %) UC patients (p = 0.014). Infection with Blastocystis is significantly less frequent in UC patients as compared to healthy controls.}, }
@article {pmid25677705, year = {2015}, author = {Rao, K and Young, VB}, title = {Fecal microbiota transplantation for the management of Clostridium difficile infection.}, journal = {Infectious disease clinics of North America}, volume = {29}, number = {1}, pages = {109-122}, pmid = {25677705}, issn = {1557-9824}, support = {UL1 TR000433/TR/NCATS NIH HHS/United States ; R01 GM099549/GM/NIGMS NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; P30 AG024824/AG/NIA NIH HHS/United States ; U19-AI090871/AI/NIAID NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; 2UL1TR000433/TR/NCATS NIH HHS/United States ; AG-024824/AG/NIA NIH HHS/United States ; }, mesh = {Biological Therapy/*methods ; *Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Disease Management ; Feces/*microbiology ; Gastrointestinal Tract/microbiology ; Humans ; Intestinal Diseases/*microbiology/therapy ; Microbiota ; }, abstract = {This article discusses the use of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). The disruption of the normal gut microbiota is central to the pathogenesis of CDI, and disruption persists in recurrent disease. The use of FMT for recurrent CDI is characterized by a high response rate and short term safety is excellent, although the long-term effects of FMT are as yet unknown.}, }
@article {pmid25677629, year = {2015}, author = {Porter, RJ and Fogg, C}, title = {Faecal microbiota transplantation for Clostridium difficile infection in the United Kingdom.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {21}, number = {6}, pages = {578-582}, doi = {10.1016/j.cmi.2015.01.020}, pmid = {25677629}, issn = {1469-0691}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*microbiology/*therapy ; Enterocolitis/*microbiology/*therapy ; Fecal Microbiota Transplantation/*methods/statistics &amp; numerical data ; Humans ; Surveys and Questionnaires ; United Kingdom ; }, abstract = {Faecal microbiota transplantation (FMT) has been shown to be highly effective in treating recurrent Clostridium difficile infection, but to date there have been no data from the United Kingdom. An electronic survey was developed at Portsmouth Hospitals' National Health Service (NHS) Trust and sent out to UK hospital specialists utilizing the contact databases of the British Infection Association and the Royal College of Gastroenterologists. A total of 162 responses were received, representing nearly one in every seven of the United Kingdom's infection specialists and a response from one in every two UK NHS acute trusts or boards. Ninety-six per cent believe that the evidence base supports the use of FMT, and 94% reported consulting on at least one patient a year in whom they would recommend FMT. However, only 22% reported FMT use in their institution in the last 10 years, and 6% reported performing more than ten FMTs in the last 10 years. Concerns with patient acceptance, donor selection, availability of screened faecal solution, feasibility of procedure and availability of local expertise were reported as inhibiting the use of FMT. More than 90% of respondents would like access to regional guidelines, prescreened faecal solution and expert advice to facilitate implementation, and more than two thirds of respondents would support a regional FMT referral centre. A large gap exists in the United Kingdom between physicians desire to use FMT and the ability and facilities to provide it as a therapy at the bedside.}, }
@article {pmid25675780, year = {2014}, author = {Degtiarenko, SP}, title = {[Efficacy of application of sphincter-preserving surgeries in the treatment of complex rectal fistulas].}, journal = {Klinichna khirurhiia}, volume = {}, number = {10}, pages = {16-19}, pmid = {25675780}, issn = {0023-2130}, mesh = {Adult ; Anal Canal/pathology/*surgery ; Fecal Incontinence/*physiopathology ; Female ; Hemorrhage/*physiopathology ; Humans ; *Intraoperative Complications ; Ligation/methods ; Male ; Middle Aged ; *Postoperative Complications ; Quality of Life ; Rectal Fistula/pathology/*surgery ; Recurrence ; Surgical Flaps/transplantation ; Treatment Outcome ; }, abstract = {The methods of sphincterpreserving operative interventions, and a principally new algorithm of treatment was elaborated for enhancing of the treatment efficacy in patients, suffering complex rectal fistulas. There were examined 291 patients, ageing 20 - 62 yrs old, all of whom operated on in Odessa Rural Clinical Hospital in 2003 - 2014 yrs for complex transsphincteric and extrasphincteric rectal fistulas. In 120 patients (I clinical group) a ligature method in accordance to standard procedure was applied; in 108 (II group)--a plastic method with transposition of mucosa-submucosal flap in accordance to original procedure; in 63 (III group)--a method of intrasphincteric ligature of complex rectal fistulas. Application of plastic method of intrasphincteric ligature of complex rectal fistulas have permitted to omit the anal incontinence, to reduce the unemployment period in 2 - 2.5 times. But a recurrence rate after sphincterpreserving operations is certainly bigger: while a ligature method application--by 5%, of a plastic one--11.1%, of intrasphincteric ligature--9.2%. Application of elaborated algorithm for the patients treatment for complex rectal fistulas have promoted preservation of high quality of life in 96.3% patients, as well as reduction of rate of their disabling.}, }
@article {pmid25665875, year = {2015}, author = {Berg, D and Clemente, JC and Colombel, JF}, title = {Can inflammatory bowel disease be permanently treated with short-term interventions on the microbiome?.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {9}, number = {6}, pages = {781-795}, doi = {10.1586/17474124.2015.1013031}, pmid = {25665875}, issn = {1747-4132}, mesh = {Anti-Bacterial Agents/adverse effects/*therapeutic use ; Colitis, Ulcerative/diagnosis/diet therapy/microbiology/*therapy ; Crohn Disease/diagnosis/diet therapy/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Intestines/*microbiology ; *Microbiota ; Probiotics/adverse effects/*therapeutic use ; Recurrence ; Remission Induction ; Time Factors ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis, is a chronic, relapsing and remitting set of conditions characterized by an excessive inflammatory response leading to the destruction of the gastrointestinal tract. While the exact etiology of inflammatory bowel disease remains unclear, increasing evidence suggests that the human gastrointestinal microbiome plays a critical role in disease pathogenesis. Manipulation of the gut microbiome has therefore emerged as an attractive alternative for both prophylactic and therapeutic intervention against inflammation. Despite its growing popularity among patients, review of the current literature suggests that the adult microbiome is a highly stable structure resilient to short-term interventions. In fact, most evidence to date demonstrates that therapeutic agents targeting the microflora trigger rapid changes in the microbiome, which then reverts to its pre-treatment state once the therapy is completed. Based on these findings, our ability to treat inflammatory bowel disease through short-term manipulations of the human microbiome may only have a transient effect. Thus, this review is intended to highlight the use of various therapeutic options, including diet, pre- and probiotics, antibiotics and fecal microbiota transplant, to manipulate the microbiome, with specific attention to the alterations made to the microflora along with the duration of impact.}, }
@article {pmid25658573, year = {2015}, author = {Porter, RJ}, title = {Pulsed faecal microbiota transplantation for recalcitrant recurrent Clostridium difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {21}, number = {3}, pages = {e23-4}, doi = {10.1016/j.cmi.2014.10.005}, pmid = {25658573}, issn = {1469-0691}, mesh = {Clostridioides difficile/*physiology ; Clostridium Infections/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Recurrence ; }, }
@article {pmid25651995, year = {2015}, author = {Scott, KP and Antoine, JM and Midtvedt, T and van Hemert, S}, title = {Manipulating the gut microbiota to maintain health and treat disease.}, journal = {Microbial ecology in health and disease}, volume = {26}, number = {}, pages = {25877}, pmid = {25651995}, issn = {0891-060X}, abstract = {BACKGROUND: The intestinal microbiota composition varies between healthy and diseased individuals for numerous diseases. Although any cause or effect relationship between the alterations in the gut microbiota and disease is not always clear, targeting the intestinal microbiota might offer new possibilities for prevention and/or treatment of disease.<br><br>OBJECTIVE: Here we review some examples of manipulating the intestinal microbiota by prebiotics, probiotics, and fecal microbial transplants.<br><br>RESULTS: Prebiotics are best known for their ability to increase the number of bifidobacteria. However, specific prebiotics could potentially also stimulate other species they can also stimulate other species associated with health, like Akkermansia muciniphila, Ruminococcus bromii, the Roseburia/Enterococcus rectale group, and Faecalibacterium prausnitzii. Probiotics have beneficial health effects for different diseases and digestive symptoms. These effects can be due to the direct effect of the probiotic bacterium or its products itself, as well as effects of the probiotic on the resident microbiota. Probiotics can influence the microbiota composition as well as the activity of the resident microbiota. Fecal microbial transplants are a drastic intervention in the gut microbiota, aiming for total replacement of one microbiota by another. With numerous successful studies related to antibiotic-associated diarrhea and Clostridium difficile infection, the potential of fecal microbial transplants to treat other diseases like inflammatory bowel disease, irritable bowel syndrome, and metabolic and cardiovascular disorders is under investigation.<br><br>CONCLUSIONS: Improved knowledge on the specific role of gut microbiota in prevention and treatment of disease will help more targeted manipulation of the intestinal microbiota. Further studies are necessary to see the (long term) effects for health of these interventions.}, }
@article {pmid25647155, year = {2015}, author = {Suskind, DL and Brittnacher, MJ and Wahbeh, G and Shaffer, ML and Hayden, HS and Qin, X and Singh, N and Damman, CJ and Hager, KR and Nielson, H and Miller, SI}, title = {Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn's disease.}, journal = {Inflammatory bowel diseases}, volume = {21}, number = {3}, pages = {556-563}, pmid = {25647155}, issn = {1536-4844}, support = {KL2 TR000421/TR/NCATS NIH HHS/United States ; P30 DK089507/DK/NIDDK NIH HHS/United States ; UL1 TR000423/TR/NCATS NIH HHS/United States ; UL1TR000423/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; *Biological Therapy ; Child ; Computational Biology ; Crohn Disease/microbiology/physiopathology/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Metagenome ; *Microbiota ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: Crohn's disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbial transplant (FMT) is a potential therapeutic option for individuals with CD based on the hypothesis that changing the fecal dysbiosis could promote less intestinal inflammation.<br><br>METHODS: Nine patients, aged 12 to 19 years, with mild-to-moderate symptoms defined by Pediatric Crohn's Disease Activity Index (PCDAI of 10-29) were enrolled into a prospective open-label study of FMT in CD (FDA IND 14942). Patients received FMT by nasogastric tube with follow-up evaluations at 2, 6, and 12 weeks. PCDAI, C-reactive protein, and fecal calprotectin were evaluated at each study visit.<br><br>RESULTS: All reported adverse events were graded as mild except for 1 individual who reported moderate abdominal pain after FMT. All adverse events were self-limiting. Metagenomic evaluation of stool microbiome indicated evidence of FMT engraftment in 7 of 9 patients. The mean PCDAI score improved with patients having a baseline of 19.7 &#xb1; 7.2, with improvement at 2 weeks to 6.4 &#xb1; 6.6 and at 6 weeks to 8.6 &#xb1; 4.9. Based on PCDAI, 7 of 9 patients were in remission at 2 weeks and 5 of 9 patients who did not receive additional medical therapy were in remission at 6 and 12 weeks. No or modest improvement was seen in patients who did not engraft or whose microbiome was most similar to their donor.<br><br>CONCLUSIONS: This is the first study to demonstrate that FMT for CD may be a possible therapeutic option for CD. Further prospective studies are required to fully assess the safety and efficacy of the FMT in patients with CD.}, }
@article {pmid25644687, year = {2015}, author = {Altomare, DF and Giuratrabocchetta, S and Knowles, CH and Muñoz Duyos, A and Robert-Yap, J and Matzel, KE and , }, title = {Long-term outcomes of sacral nerve stimulation for faecal incontinence.}, journal = {The British journal of surgery}, volume = {102}, number = {4}, pages = {407-415}, doi = {10.1002/bjs.9740}, pmid = {25644687}, issn = {1365-2168}, mesh = {Aged ; Electric Stimulation Therapy/*methods ; Electrodes, Implanted ; Fecal Incontinence/etiology/*therapy ; Female ; Humans ; *Lumbosacral Plexus ; Male ; Middle Aged ; Prospective Studies ; ROC Curve ; Treatment Outcome ; }, abstract = {BACKGROUND: Sacral nerve stimulation (SNS) has proven short- to medium-term effectiveness for the treatment of faecal incontinence (FI); fewer long-term outcomes have been presented and usually in small series. Here, the long-term effectiveness of SNS was evaluated in a large European cohort of patients with a minimum of 5 years' follow-up.<br><br>METHODS: Prospectively registered data from patients with FI who had received SNS for at least 5&#x2009;years from ten European centres were collated by survey. Daily stool diaries, and Cleveland Clinic and St Mark's incontinence scores were evaluated at baseline, after implantation and at the last follow-up. SNS was considered successful when at least 50 per cent symptom improvement was maintained at last follow-up.<br><br>RESULTS: A total of 407 patients underwent temporary stimulation, of whom 272 (66&#xb7;8 per cent) had an impulse generator implanted; 228 (56&#xb7;0 per cent) were available for long-term follow-up at a median of 84 (i.q.r. 70-113) months. Significant reductions in the number of FI episodes per week (from median 7 to 0&#xb7;25) and summative symptom scores (median Cleveland Clinic score from 16 to 7, St Mark's score from 19 to 6) were recorded after implantation (all P <&#x2009;0&#xb7;001) and maintained in long-term follow-up. In per-protocol analysis, long-term success was maintained in 71&#xb7;3 per cent of patients and full continence was achieved in 50&#xb7;0 per cent; respective values based on intention-to-treat analysis were 47&#xb7;7 and 33&#xb7;4 per cent. Predictive analyses determined no significant association between pretreatment variables and successful outcomes. Risk of long-term failure correlated with minor symptom score improvement during the temporary test phase.<br><br>CONCLUSION: SNS remains an effective treatment for FI in the long term for approximately half of the patients starting therapy.}, }
@article {pmid25643728, year = {2015}, author = {Barazesh, A and Fouladvand, M and Tahmasebi, R and Heydari, A and Fallahi, J}, title = {The prevalence of intestinal parasites in hemodialysis patients in Bushehr, Iran.}, journal = {Hemodialysis international. International Symposium on Home Hemodialysis}, volume = {19}, number = {3}, pages = {447-451}, doi = {10.1111/hdi.12272}, pmid = {25643728}, issn = {1542-4758}, mesh = {Adult ; Aged ; Animals ; Cross-Sectional Studies ; Female ; Humans ; Intestinal Diseases, Parasitic/*etiology ; Iran/epidemiology ; Male ; Middle Aged ; Parasites/*growth &amp; development ; Prevalence ; Renal Dialysis/*adverse effects ; }, abstract = {Hemodialysis patients, due to a dysfunction of the immune response, are prone to a variety of opportunistic infections. Studies of intestinal parasitic infections in these patients are limited. Therefore, the present study was performed to determine the prevalence of these infections in patients on hemodialysis in Bushehr. In this cross-sectional study, fecal samples have been collected from all hemodialysis patients who were continuously referred from September 2011 to September 2012 to the dialysis center at Bushehr and tested using routine parasitological methods. From a total of 88 patients studied, 25 patients (28.4%) were infected with one or more intestinal parasites. Blastocystis hominis and Entamoeba coli with 13.6% and 6.7% prevalence had the highest prevalence among the patients, respectively. The age group 51-70 years had the highest rates of infection. Statistical analysis showed no relationship between sex and the risk of intestinal parasites. Seventeen percent of infected patients showed up with diarrhea and this relationship was statistically significant. Considering the high prevalence of intestinal parasitic infection among hemodialysis patients in Bushehr and also the high probability of infection in these patients, it is recommended that periodic examinations and screening patients during dialysis and before kidney transplantation should be a part of routine medical care.}, }
@article {pmid25643269, year = {2015}, author = {Korman, TM}, title = {Diagnosis and management of Clostridium difficile infection.}, journal = {Seminars in respiratory and critical care medicine}, volume = {36}, number = {1}, pages = {31-43}, doi = {10.1055/s-0034-1398741}, pmid = {25643269}, issn = {1098-9048}, mesh = {Adult ; Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*drug effects/pathogenicity ; Clostridium Infections/*diagnosis/*drug therapy/microbiology ; Cross Infection ; Humans ; Recurrence ; }, abstract = {There have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease, attributed to the emergence of a fluoroquinolone-resistant "hypervirulent" strain, ribotype 027. C. difficile is now the most common pathogen causing hospital-acquired infection in U.S. hospitals, and community-acquired infections are increasing. The diagnosis of CDI is based on a combination of signs and symptoms, confirmed by laboratory tests. Clinical manifestations of CDI can range from asymptomatic colonization to severe pseudomembranous colitis and death. Many aspects of laboratory diagnosis of CDI remain contentious. Toxin enzyme immunoassays are too insensitive to be used alone, while nucleic acid amplification tests have emerged as an option, either as a stand-alone test or as part of a multitest algorithm. Oral vancomycin and metronidazole have been the recommended antimicrobial therapy options, and fidaxomicin is an effective new alternative. There is ongoing concern regarding the potential inferiority of metronidazole, in particular for severe CDI. Management of severe CDI and recurrent CDI continue to represent major treatment challenges. Biological therapies for the restoration of the intestinal microbiota (e.g., fecal microbiota transplantation) and monoclonal antibody therapy are promising approaches for CDI management, in particular troublesome recurrent CDI. This review will concentrate on the diagnosis and management of CDI in adults.}, }
@article {pmid25636927, year = {2015}, author = {Tvede, M and Tinggaard, M and Helms, M}, title = {Rectal bacteriotherapy for recurrent Clostridium difficile-associated diarrhoea: results from a case series of 55 patients in Denmark 2000-2012.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {21}, number = {1}, pages = {48-53}, doi = {10.1016/j.cmi.2014.07.003}, pmid = {25636927}, issn = {1469-0691}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteria ; Biological Therapy/*methods ; *Clostridioides difficile ; Clostridium Infections/epidemiology/*therapy ; Denmark/epidemiology ; Feces/*microbiology ; Female ; Hospitalization/statistics &amp; numerical data ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Young Adult ; }, abstract = {Clostridium difficile infection is one of the most common nosocomial infections. Among other alternatives to standard treatment with vancomycin for recurrent infection are faecal microbiota transplantation and rectal bacteriotherapy with a fixed mixture of intestinal bacterial strains isolated from faeces of healthy persons to mimic a theoretical normal microflora. Developed by Dr. Tvede and Dr. Rask-Madsen, the latter method has been in use for selected patients during the last 25 years in Denmark. In this study we reviewed the medical records of patients treated with rectal bacteriotherapy for relapsing C. difficile in Denmark, 2000-2012. The primary end point was recurrent diarrhoea within 30 days after treatment. A total of 55 patients were included in this case series. Thirty-five patients (64%) had no recurrence within 30 days of bacteriotherapy. Patients with recurrence tended to be older (75.8 years vs. 61.3 years; p 0.26), and more often have preexisting gastrointestinal illness and longer duration of time from the first CDI to bacteriotherapy (221.6 days vs. 175.3 days; p 0.18). Treatment success was 80% in the subgroup of patients with no known gastrointestinal illness and first C. difficile episode less than 6 months before bacteriotherapy. The most common adverse events were abdominal pain (10.9%) and worsening diarrhoea (4.3%). One patient was hospitalized 10 days after treatment with appendicitis, fever, and Escherichia coli bacteremia. The results from this study indicate that rectal bacteriotherapy is a viable alternative to faecal microbiota transplantation in patients with relapsing C. difficile-associated diarrhoea.}, }
@article {pmid25628851, year = {2015}, author = {Dehghani, SM and Kulouee, N and Honar, N and Imanieh, MH and Haghighat, M and Javaherizadeh, H}, title = {Clinical Manifestations among Children with Chronic Functional Constipation.}, journal = {Middle East journal of digestive diseases}, volume = {7}, number = {1}, pages = {31-35}, pmid = {25628851}, issn = {2008-5230}, abstract = {BACKGROUND Constipation is one of the most frequent cause of patient visits to pediatric gastroenterology clinics. Early diagnosis and treatment is important. There are few studies about clinical manifestations of constipation in children. We aimed to find the relative frequency of gastrointestinal manifestations of constipation among constipated children. METHODS This cross-sectional study was carried out on children aged < 18 years old with chronic functional constipation referred to Imam Reza Clinic of Shiraz University of Medical Sciences. Children with organic causes of chronic constipation were excluded from study. Rome III criteria were used for defining constipation. The duration of study was 1 year starting from September 2010. Abdominal pain, fecal mass, rectal bleeding, anorexia, fecal soiling, retentive posture, withholding behavior, anal fissure, and peri-anal erythema were recorded for each case based on history and physical examination. Data were analyzed using SPSS software, version 13.0 (Chicago, IL, USA). RESULTS Of 222 children with functional constipation, 124(55.9%) were girls and 98 (44.1%) were boys with a mean ± SD age of 5±3.12 years. The mean ± SD duration of constipation was 2.2±1.9 years. Large and hard stool was present in 93.7% of the patients. Painful defecation and withholding behavior were seen in 92.3% and 91.9% of the patients, respectively. Fecal impaction was more frequent among boys compared with girls (p<0.01). Fecal soiling was present in 40.8% of the boys and 28.2% of the girls (p=0.04). CONCLUSION Large and hard stool, painful defecation and withholding behavior were the most frequent signs or symptoms among children with chronic functional constipation. Fresh rectal bleeding and anal fissure were the least frequent signs and symptoms in this group.}, }
@article {pmid25626036, year = {2015}, author = {Bagdasarian, N and Rao, K and Malani, PN}, title = {Diagnosis and treatment of Clostridium difficile in adults: a systematic review.}, journal = {JAMA}, volume = {313}, number = {4}, pages = {398-408}, pmid = {25626036}, issn = {1538-3598}, support = {UL1 TR000433/TR/NCATS NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; P30 AG024824/AG/NIA NIH HHS/United States ; 2UL1TR000433/TR/NCATS NIH HHS/United States ; AG-024824/AG/NIA NIH HHS/United States ; 1U19AI090871-01/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/*diagnosis/*drug therapy ; Humans ; }, abstract = {IMPORTANCE: Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased.<br><br>OBJECTIVE: To review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age &#x2265; 18 years).<br><br>EVIDENCE REVIEW: Ovid MEDLINE and Cochrane databases were searched using keywords relevant to the diagnosis and treatment of CDI in adults. Articles published between January 1978 and October 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a guideline, systematic review, or meta-analysis published within the past 10 years. Of 4682 articles initially identified, 196 were selected for full review. Of these, the most pertinent 116 articles were included. Clinical trials, large observational studies, and more recently published articles were prioritized in the selection process.<br><br>FINDINGS: Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C difficile. Diagnostic approaches are complex due to the availability of multiple testing strategies. Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single-step PCR on liquid stool samples have the best test performance characteristics (for multistep: sensitivity was 0.68-1.00 and specificity was 0.92-1.00; and for single step: sensitivity was 0.86-0.92 and specificity was 0.94-0.97). Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases of CDI. Recent data demonstrate clinical success rates of 66.3% for metronidazole vs 78.5% for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P =&#x2009;.005) and fecal microbiota transplantation (response rates of 83%-94% for recurrent CDI).<br><br>CONCLUSIONS AND RELEVANCE: Diagnostic testing for CDI should be performed only in symptomatic patients. Treatment strategies should be based on disease severity, history of prior CDI, and the individual patient's risk of recurrence. Vancomycin is the treatment of choice for severe or complicated CDI, with or without adjunctive therapies. Metronidazole is appropriate for mild disease. Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence. Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.}, }
@article {pmid25623242, year = {2015}, author = {Vigvári, S and Nemes, Z and Vincze, &#xc1; and Solt, J and Sipos, D and Feiszt, Z and Kovács, B and Bartos, B and Péterfi, Z}, title = {Faecal microbiota transplantation in Clostridium difficile infections.}, journal = {Infectious diseases (London, England)}, volume = {47}, number = {2}, pages = {114-116}, doi = {10.3109/00365548.2014.969305}, pmid = {25623242}, issn = {2374-4243}, mesh = {Biological Therapy/*methods ; Clostridium Infections/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; *Secondary Prevention ; }, }
@article {pmid25605402, year = {2015}, author = {Lorenz, F and Marklund, S and Werner, M and Palmqvist, R and Wahlin, BE and Wahlin, A}, title = {Fecal calprotectin as a biomarker of intestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {7920}, pmid = {25605402}, issn = {2045-2322}, mesh = {Adolescent ; Adult ; Aged ; Allografts ; *Feces ; Female ; Graft vs Host Disease/*metabolism/pathology ; Hematologic Neoplasms/metabolism/pathology/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Intestinal Diseases/*metabolism/pathology ; Leukocyte L1 Antigen Complex/*metabolism ; Male ; Middle Aged ; }, abstract = {The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on clinical symptoms and histological findings. In clinical practice, it is often difficult to decide whether abdominal symptoms in an allogeneic transplant recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful in establishing the diagnosis, but endoscopy is not always possible to perform due to poor general condition of the patients. No biomarkers are routinely used to predict GVHD. The aim of fecal calprotectin and alpha-1 antitrypsin testing in our study was to find out whether determination of the concentrations of these proteins may be used as a screening method for enteric GVHD. We studied prospectively 51 patients, 8 of whom developed GI-GVHD. Our data demonstrate that elevated fecal calprotectin levels were significantly associated with presence of GI-GVHD. We found a positive association between high F-calprotectin and severe gastrointestinal GVHD. In bivariate analysis, only calprotectin but not alpha-1 antitrypsin was independently associated with GI-GVHD. Testing for fecal calprotectin after allogeneic stem cell transplantation may be a useful screening tool.}, }
@article {pmid25598718, year = {2014}, author = {Ray, A and Smith, R and Breaux, J}, title = {Fecal Microbiota Transplantation for Clostridium difficile Infection: The Ochsner Experience.}, journal = {Ochsner journal}, volume = {14}, number = {4}, pages = {538-544}, pmid = {25598718}, issn = {1524-5012}, abstract = {BACKGROUND: Clostridium difficile infection (CDI) accounts for 20%-30% of cases of antibiotic-associated diarrhea and is the most commonly recognized cause of infectious diarrhea in healthcare settings. The incidence of CDI is rising, while the effectiveness of antibiotics for treatment decreases with recurrent episodes. The use of fecal microbiota transplantation (FMT) for cure of CDI has been reported since 1958, and the worldwide cure rate is reported to be 93%. We report our experience with FMT for the treatment of CDI.<br><br>METHODS: We performed a retrospective chart review of patients undergoing FMT for CDI at Ochsner Clinic Foundation from August 2012 to November 2013. FMT was administered via colonoscopy for patients with recurrent or severe CDI. Stool donors were screened for infections in the majority of cases.<br><br>RESULTS: FMT was performed in 20 CDI patients. The 16 female and 4 male patients ranged in age from 27 to 89 years (mean 62 years). The average duration of illness from diagnosis to treatment was 49.6 weeks, based on available data. Only 3 donors were unscreened for infectious pathogens. Nine donors were related to the recipients by blood; most of the other donors were spouses. The average length of follow-up after FMT was 3 months. No recurrences of CDI after treatment have been documented. Adverse events reported after treatment included abdominal cramping, bloating, flatulence, and nausea that resolved.<br><br>CONCLUSION: Although the US Food and Drug Administration currently considers FMT an experimental therapy, we demonstrate that FMT is safe, well tolerated, and effective for recurrent and severe CDI.}, }
@article {pmid25598276, year = {2015}, author = {van Montfrans, J and Schulz, L and Versluys, B and de Wildt, A and Wolfs, T and Bierings, M and Gerhardt, C and Lindemans, C and Wensing, A and Boelens, JJ}, title = {Viral PCR positivity in stool before allogeneic hematopoietic cell transplantation is strongly associated with acute intestinal graft-versus-host disease.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {21}, number = {4}, pages = {772-774}, doi = {10.1016/j.bbmt.2015.01.009}, pmid = {25598276}, issn = {1523-6536}, mesh = {Adolescent ; Adult ; Allografts ; Child ; Child, Preschool ; *DNA Viruses ; *DNA, Viral ; Disease-Free Survival ; Feces/*virology ; Female ; Follow-Up Studies ; *Graft vs Host Disease/mortality/prevention &amp; control/virology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Intestinal Diseases/*virology ; Male ; *Neoplasms/mortality/therapy ; *Polymerase Chain Reaction ; Survival Rate ; }, abstract = {Acute graft-versus-host disease (aGVHD) can be triggered by inflammatory conditions, including infections and mucositis. We investigated the association between PCR positivity for gastrointestinal (GI) viruses in stool before hematopoietic cell transplantation (HCT) and intestinal aGVHD using Cox proportional hazard models. We included 48 consecutive HCT patients (28 with malignancies and 20 with nonmalignancies) without GI symptoms before HCT. Fifteen patients were GI virus positive: 9 adenovirus, 3 norovirus, 2 parechovirus, and 1 astrovirus. Overall survival was 58% ± 8%. The cumulative incidence of aGVHD grade 2 to 4 was 43% ± 8% (n = 18) after a median of 47 days (range, 14 to 140). In univariate analysis, GI virus PCR positivity was the only predictor for aGVHD (P = .008): within the group of GI virus PCR-positive patients, the cumulative incidence of aGVHD 2 to 4 was 70% ± 12% versus 29 ± 8% in the PCR-negative group (P = .004). In conclusion, GI virus PCR positivity before HCT predicted development of intestinal aGVHD. These results may ultimately affect monitoring, aGVHD prophylaxis, and treatment, as well as rescheduling of elective HCTs.}, }
@article {pmid25596117, year = {2015}, author = {Gu, SL and Chen, YB and Lv, T and Zhang, XW and Wei, ZQ and Shen, P and Li, LJ}, title = {Risk factors, outcomes and epidemiology associated with Clostridium difficile infection in patients with haematological malignancies in a tertiary care hospital in China.}, journal = {Journal of medical microbiology}, volume = {64}, number = {Pt 3}, pages = {209-216}, doi = {10.1099/jmm.0.000028}, pmid = {25596117}, issn = {1473-5644}, mesh = {Adolescent ; Adult ; Aged ; Anti-Infective Agents/therapeutic use ; Antineoplastic Agents, Phytogenic/*therapeutic use ; China/epidemiology ; Clostridioides difficile/classification/genetics/*isolation &amp; purification ; Clostridium Infections/blood/drug therapy/*epidemiology/microbiology ; Cross Infection ; Enterocolitis, Pseudomembranous/blood/drug therapy/epidemiology/microbiology ; Etoposide/*therapeutic use ; Feces/microbiology ; Female ; Hematologic Neoplasms/*complications/drug therapy/therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Incidence ; Male ; Middle Aged ; Multilocus Sequence Typing ; Retrospective Studies ; Ribotyping ; Risk Factors ; Tertiary Care Centers ; Young Adult ; }, abstract = {The purpose of this study was to evaluate the risk factors, outcomes and epidemiology associated with Clostridium difficile infection (CDI) in patients with haematological malignancies in a tertiary care hospital in China. C. difficile screening was performed on patients admitted for chemotherapy or haematopoietic stem cell transplantation between 2009 and 2013. C. difficile isolates were analysed by multilocus sequence typing, and a retrospective chart review was performed on all patients with a positive toxin assay. CDI was diagnosed in 21 haematology-oncology ward patients and 14 marrow transplantation service patients for a cumulative incidence of 1.89/1000 and 3.69/1000 patient-days, respectively. Univariate analyses showed that patients who received etoposide had an increased risk of CDI (odds ratio 4.25, 95 % confidence interval 1.32-13.64). There was only one patient death, for which CDI was not the primary cause. Ten sequence types (STs) were identified, of which ST-3 and ST-54 were the most common; the hypervirulent ST-1 (ribotype 027) and ST-11 (ribotype 078) C. difficile strains were not detected in the patients in this study. The incidence of CDI did not differ between patients receiving chemotherapy and those receiving haematopoietic stem cell transplantation. The only risk factor for chemotherapy patients was treatment with etoposide.}, }
@article {pmid25595930, year = {2015}, author = {Hansen, JJ and Sartor, RB}, title = {Therapeutic Manipulation of the Microbiome in IBD: Current Results and Future Approaches.}, journal = {Current treatment options in gastroenterology}, volume = {13}, number = {1}, pages = {105-120}, pmid = {25595930}, issn = {1092-8472}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; }, abstract = {Despite recent major strides in our understanding of the genetic and microbial influences that contribute to the development of the inflammatory bowel diseases (IBDs), their etiology continues to be enigmatic. Results from experiments in animal models of IBDs overwhelmingly support a causal role of the microbiota in these diseases, though whether such a cause-effect relationship exists in human IBDs is still uncertain. Therefore, virtually all currently approved and most often prescribed treatments for IBDs are directed toward the over-active immune response in these diseases rather than the intestinal bacteria. Nevertheless, there is an important need for non-immunosuppressive therapies that may present a more favorable risk-benefit profile such as those that selectively target the disruptions in gut microbiota that accompany IBDs. This need has led to clinical trials of various microbial-directed therapies including fecal microbial transplant, antibiotics, probiotics, and prebiotics. Unfortunately, these published studies, many of which are small, have generally failed to demonstrate a consistent benefit of these agents in IBDs, thus leading to slow acceptance of microbe-focused treatments for these conditions. In this article, we review and summarize the microbial basis for IBDs and the results of the most recent trials of fecal microbial transplant, antibiotics, probiotics, and prebiotics in IBDs. We also comment on possible safety concerns with these agents, speculate on why they have failed to show efficacy in certain clinical settings, and propose strategies to improve their usefulness.}, }
@article {pmid25595150, year = {2015}, author = {Chuong, KH and O'Doherty, KC and Secko, DM}, title = {Media Discourse on the Social Acceptability of Fecal Transplants.}, journal = {Qualitative health research}, volume = {25}, number = {10}, pages = {1359-1371}, doi = {10.1177/1049732314568199}, pmid = {25595150}, issn = {1049-7323}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Canada ; Fecal Microbiota Transplantation/*psychology ; Gastrointestinal Microbiome ; Humans ; Mass Media/*statistics &amp; numerical data ; }, abstract = {Advances in human microbiome research have generated considerable interest in elucidating the role of bacteria in health and the application of microbial ecosystem therapies and probiotics. Fecal transplants involve the introduction of gut microbes from a healthy donor's stool to the patient and have been documented as effective for treating Clostridium difficile infections (CDIs) and some other gastrointestinal disorders. However, the treatment has encountered regulatory hurdles preventing widespread uptake. We examined dominant representations of fecal transplants in Canadian media and found that fecal transplants are often represented as being inherently disgusting or distasteful (the "ick factor"). This "ick factor" is used to construct different messages about the treatment's social acceptability and legitimacy. We conclude that an over-emphasis on the "ick factor" constrains public discourse from a more nuanced discussion of the social challenges, scientific concerns, and regulatory issues surrounding the treatment.}, }
@article {pmid25592048, year = {2015}, author = {Oh, HK and Lee, HS and Lee, JH and Oh, SH and Lim, JY and Ahn, S and Kang, SB}, title = {Coadministration of basic fibroblast growth factor-loaded polycaprolactone beads and autologous myoblasts in a dog model of fecal incontinence.}, journal = {International journal of colorectal disease}, volume = {30}, number = {4}, pages = {549-557}, pmid = {25592048}, issn = {1432-1262}, mesh = {Anal Canal/physiopathology ; Animals ; Disease Models, Animal ; Dogs ; Drug Carriers ; Fecal Incontinence/pathology/physiopathology/*therapy ; Fibroblast Growth Factor 2/*administration &amp; dosage ; Guided Tissue Regeneration/*methods ; Muscle Contraction ; Myoblasts/*transplantation ; Polyesters ; Pressure ; Random Allocation ; Transplantation, Autologous ; }, abstract = {PURPOSE: Basic fibroblastic growth factor (bFGF), a member of the heparin-binding growth factor family, regulates muscle differentiation. We investigated whether coadministration of autologous myoblasts and bFGF-loaded polycaprolactone beads could improve sphincter recovery in a dog model of fecal incontinence (FI).<br><br>METHODS: FI was induced by resecting 25% of the posterior anal sphincter in ten mongrel dogs. One month later, the dogs were randomized to receive either PKH-26-labeled autologous myoblasts alone (M group, five dogs) or autologous myoblasts and bFGF-loaded polycaprolactone beads (MBG group, five dogs). The outcomes included anal manometry, compound muscle action potentials (CMAPs) of the pudendal nerve, and histology.<br><br>RESULTS: The increase in anal contractile pressure over 3 months was significantly greater in the MBG group (from 4.85 to 6.83 mmHg) than that in the M group (from 4.94 to 4.25 mmHg), with a coefficient for the difference in recovery rate of 2.672 (95% confidence interval [CI] 0.962 to 4.373, p&#x2009;=&#x2009;0.002). The change in the CMAP amplitude was also significantly greater in the MBG group (from 0.59 to 1.56 mV) than that in the M group (from 0.81 to 0.67 mV) (coefficient 1.114, 95% CI 0.43 to 1.80, p&#x2009;=&#x2009;0.001). Labeled cells were detected in 2/5 (40%) and 5/5 (100%) dogs in the M and MBG groups, respectively.<br><br>CONCLUSION: Coadministration of bFGF-loaded PCL beads and autologous myoblasts improved the recovery of sphincter function in a dog model of FI and had better outcomes than cell-based therapy alone.}, }
@article {pmid25587656, year = {2015}, author = {Keller, JJ and Kuijper, EJ}, title = {Treatment of recurrent and severe Clostridium difficile infection.}, journal = {Annual review of medicine}, volume = {66}, number = {}, pages = {373-386}, doi = {10.1146/annurev-med-070813-114317}, pmid = {25587656}, issn = {1545-326X}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/chemically induced/microbiology/*therapy ; Feces/*microbiology ; Fidaxomicin ; Humans ; Metronidazole/therapeutic use ; *Microbiota ; Recurrence ; Severity of Illness Index ; Transplantation/*methods ; Vancomycin/therapeutic use ; }, abstract = {Clostridium difficile infection (CDI) is a serious complication of hospitalization and antibiotic use with a high mortality and very high costs. Despite appropriate treatment, a subset of patients develop chronic recurrent CDI. Some other patients develop severe and life-threatening colitis. The risk factors, pathogenesis, and treatment of recurrent CDI and severe CDI are discussed in this review. In particular, fecal microbiota transplantation (FMT) as a treatment strategy is outlined and a treatment algorithm incorporating FMT is described.}, }
@article {pmid25580765, year = {2015}, author = {Wang, XJ and Kraft, CS and Dhere, T}, title = {Use of standard donors in fecal microbiotal transplants.}, journal = {Southern medical journal}, volume = {108}, number = {1}, pages = {68-69}, doi = {10.14423/SMJ.0000000000000227}, pmid = {25580765}, issn = {1541-8243}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; *Microbiota ; Tissue Donors ; Transplantation/*methods ; *Unrelated Donors ; }, }
@article {pmid25577013, year = {2015}, author = {Barbut, F and Collignon, A and Butel, MJ and Bourlioux, P}, title = {[Fecal microbiota transplantation: review].}, journal = {Annales pharmaceutiques francaises}, volume = {73}, number = {1}, pages = {13-21}, doi = {10.1016/j.pharma.2014.05.004}, pmid = {25577013}, issn = {0003-4509}, mesh = {Clostridioides difficile ; Enterocolitis, Necrotizing/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Humans ; Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) has gained an increasing medical interest, since the recognition of the role of disturbed microbiota in the development of various diseases. To date, FMT is an established treatment modality for multiple recurrent Clostridium difficile infection (RCDI), despite lack of standardization of the procedure. Persisting normalization of the disturbed colonic microbiota associated with RCDI seems to be responsible for the therapeutic effect of FMT. For other diseases, FMT should be considered strictly experimental, only offered to patients in an investigational clinical setting. Although the concept of FMT is appealing, current expectations should be damped until future evidence arises.}, }
@article {pmid25574083, year = {2015}, author = {Xu, MQ and Cao, HL and Wang, WQ and Wang, S and Cao, XC and Yan, F and Wang, BM}, title = {Fecal microbiota transplantation broadening its application beyond intestinal disorders.}, journal = {World journal of gastroenterology}, volume = {21}, number = {1}, pages = {102-111}, pmid = {25574083}, issn = {2219-2840}, mesh = {Animals ; Biological Therapy/adverse effects/*methods ; Dysbiosis/microbiology ; Feces/*microbiology ; Host-Pathogen Interactions ; Humans ; Intestinal Diseases/diagnosis/microbiology/*therapy ; Intestines/*microbiology ; *Microbiota ; Treatment Outcome ; }, abstract = {Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson's disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.}, }
@article {pmid25574076, year = {2015}, author = {Vyas, D and Aekka, A and Vyas, A}, title = {Fecal transplant policy and legislation.}, journal = {World journal of gastroenterology}, volume = {21}, number = {1}, pages = {6-11}, pmid = {25574076}, issn = {2219-2840}, mesh = {Animals ; Biological Therapy/adverse effects/*methods ; Clostridioides difficile/*pathogenicity ; Enterocolitis, Pseudomembranous/diagnosis/epidemiology/microbiology/*therapy ; Feces/*microbiology ; *Health Policy ; Humans ; Intestines/*microbiology ; *Microbiota ; Patient Safety ; Risk Assessment ; Risk Factors ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has garnered significant attention in recent years in the face of a reemerging Clostridium difficile (C. difficile) epidemic. Positive results from the first randomized control trial evaluating FMT have encouraged the medical community to explore the process further and expand its application beyond C. difficile infections and even the gastrointestinal domain. However promising and numerous the prospects of FMT appear, the method remains limited in scope today due to several important barriers, most notably a poorly defined federal regulatory policy. The Food and Drug Administration has found it difficult to standardize and regulate the administration of inherently variable, metabolically active, and ubiquitously available fecal material. The current cumbersome policy, which classifies human feces as a drug, has prevented physicians from providing FMT and deserving patients from accessing FMT in a timely fashion, and subsequent modifications seem only to be temporary. The argument for reclassifying fecal material as human tissue is well supported. Essentially, this would allow for a regulatory framework that is sufficiently flexible to expand access to care and facilitate research, but also appropriately restrictive and centralized to ensure patient safety. Such an approach can facilitate the advancement of FMT to a more refined, controlled, and aesthetic process, perhaps in the form of a customized and well-characterized stool substitute therapy.}, }
@article {pmid25572899, year = {2015}, author = {Brown, JR and Morfopoulou, S and Hubb, J and Emmett, WA and Ip, W and Shah, D and Brooks, T and Paine, SM and Anderson, G and Virasami, A and Tong, CY and Clark, DA and Plagnol, V and Jacques, TS and Qasim, W and Hubank, M and Breuer, J}, title = {Astrovirus VA1/HMO-C: an increasingly recognized neurotropic pathogen in immunocompromised patients.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {60}, number = {6}, pages = {881-888}, pmid = {25572899}, issn = {1537-6591}, mesh = {Astroviridae Infections/diagnosis/pathology/*virology ; Base Sequence ; Biopsy ; Brain/*pathology/ultrastructure ; Encephalitis, Viral/*diagnosis/*pathology/virology ; Feces/virology ; Genome, Viral ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; *Immunocompromised Host ; Infant ; Male ; Mamastrovirus/genetics/isolation &amp; purification/*pathogenicity ; Phylogeny ; Prevalence ; RNA, Viral/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Stem Cell Transplantation ; }, abstract = {BACKGROUND: An 18-month-old boy developed encephalopathy, for which extensive investigation failed to identify an etiology, 6 weeks after stem cell transplant. To exclude a potential infectious cause, we performed high-throughput RNA sequencing on brain biopsy.<br><br>METHODS: RNA-Seq was performed on an Illumina Miseq, generating 20 million paired-end reads. Nonhost data were checked for similarity to known organisms using BLASTx. The full viral genome was sequenced by primer walking.<br><br>RESULTS: We identified an astrovirus, HAstV-VA1/HMO-C-UK1(a), which was highly divergent from human astrovirus (HAstV 1-8) genotypes, but closely related to VA1/HMO-C astroviruses, including one recovered from a case of fatal encephalitis in an immunosuppressed child. The virus was detected in stool and serum, with highest levels in brain and cerebrospinal fluid (CSF). Immunohistochemistry of the brain biopsy showed positive neuronal staining. A survey of 680 stool and 349 CSF samples identified a related virus in the stool of another immunosuppressed child.<br><br>CONCLUSIONS: The discovery of HAstV-VA1/HMO-C-UK1(a) as the cause of encephalitis in this case provides further evidence that VA1/HMO-C viruses, unlike HAstV 1-8, are neuropathic, particularly in immunocompromised patients, and should be considered in the differential diagnosis of encephalopathy. With a turnaround from sample receipt to result of <1 week, we confirm that RNA-Seq presents a valuable diagnostic tool in unexplained encephalitis.}, }
@article {pmid25567105, year = {2015}, author = {Surawicz, CM}, title = {Clostridium difficile infection: risk factors, diagnosis and management.}, journal = {Current treatment options in gastroenterology}, volume = {13}, number = {1}, pages = {121-129}, pmid = {25567105}, issn = {1092-8472}, abstract = {Clostridium difficile infection (CDI) is the leading cause of death due to gastrointestinal infections in the US and is the most common cause of nosocomial diarrhea. The emergence of a hypervirulent strain in the early 2000s has been associated with a dramatic increase in the number and severity of cases in the US, Canada, and several other countries. Most cases are related to antibiotic use, but sporadic cases occur in otherwise healthy individuals with no risk factors. Morbidity and mortality are highest in the elderly. Diagnosis is confirmed by detection of C. difficile toxin in the stools. Treatment should be stratified by severity of disease, with metronidazole use for mild disease cases and vancomycin for severe disease. Recurrent CDI occurs in 10-20 % of cases. A first recurrence can be treated with a ten-day regimen of metronidazole or vancomycin; a second recurrence is best treated by a pulsed regimen of vancomycin. In patients with multiple (three or more) recurrences, fecal microbiota transplant has a high rate of success. The most important methods of prevention are wise antibiotic policies, hand hygiene, isolation, and barrier methods in hospital and long-term care facilities (LCTF) settings.}, }
@article {pmid25567038, year = {2015}, author = {West, CE and Renz, H and Jenmalm, MC and Kozyrskyj, AL and Allen, KJ and Vuillermin, P and Prescott, SL and , }, title = {The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.}, journal = {The Journal of allergy and clinical immunology}, volume = {135}, number = {1}, pages = {3-13; quiz 14}, doi = {10.1016/j.jaci.2014.11.012}, pmid = {25567038}, issn = {1097-6825}, mesh = {Animals ; Dietary Fiber/therapeutic use ; Gastrointestinal Tract/*microbiology ; Humans ; Hypersensitivity/drug therapy ; Inflammation/drug therapy/*etiology ; *Microbiota ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention.}, }
@article {pmid25566951, year = {2015}, author = {Cadeddu, F and Salis, F and Lisi, G and Ciangola, I and Milito, G}, title = {Complex anal fistula remains a challenge for colorectal surgeon.}, journal = {International journal of colorectal disease}, volume = {30}, number = {5}, pages = {595-603}, pmid = {25566951}, issn = {1432-1262}, mesh = {Bioprosthesis ; Catheter Ablation/*methods ; Collagen/therapeutic use ; Fecal Incontinence/prevention &amp; control ; Female ; Fibrin Tissue Adhesive/*therapeutic use ; Humans ; Injections, Intralesional ; Male ; Minimally Invasive Surgical Procedures/*methods ; Prognosis ; Rectal Fistula/*pathology/*surgery ; Recurrence ; Risk Assessment ; Severity of Illness Index ; Stem Cell Transplantation/methods ; Surgical Flaps ; Treatment Outcome ; }, abstract = {AIM: Anal fistula is a common proctological problem to both patient and physician throughout surgical history. Several surgical and sphincter-sparing approaches have been described for the management of fistula-in-ano, aimed to minimize the recurrence and to preserve the continence. We aimed to systematically review the available studies relating to the surgical management of anal fistulas.<br><br>MATERIAL AND METHODS: A Medline search was performed using the PubMed, Ovid, Embase, and Cochrane databases to identify articles reporting on fistula-in-ano management, aimed to find out the current techniques available, the new technologies, and their effectiveness in order to delineate a gold standard treatment algorithm.<br><br>RESULTS: The management of low anal fistulas is usually straightforward, given that fistulotomy is quite effective, and if the fistula has been properly evaluated, continence disturbance is minimal. On the contrary, high complex fistulas are challenging, because cure and continence are directly competing priorities.<br><br>CONCLUSIONS: Conventional fistula surgery techniques have their place, but new technologies such as fibrin glues, dermal collagen injection, the anal fistula plugs, and stem cell injection offer alternative approaches whose long-term efficacy needs to be further clarified in large long-term randomized trials.}, }
@article {pmid25564777, year = {2014}, author = {Mathur, H and Rea, MC and Cotter, PD and Ross, RP and Hill, C}, title = {The potential for emerging therapeutic options for Clostridium difficile infection.}, journal = {Gut microbes}, volume = {5}, number = {6}, pages = {696-710}, pmid = {25564777}, issn = {1949-0984}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bacterial Vaccines/therapeutic use ; Clostridioides difficile/drug effects/*physiology ; Clostridium Infections/drug therapy/microbiology/*therapy ; Humans ; }, abstract = {Clostridium difficile is mainly a nosocomial pathogen and is a significant cause of antibiotic-associated diarrhea. It is also implicated in the majority of cases of pseudomembranous colitis. Recently, advancements in next generation sequencing technology (NGS) have highlighted the extent of damage to the gut microbiota caused by broad-spectrum antibiotics, often resulting in C. difficile infection (CDI). Currently the treatment of choice for CDI involves the use of metronidazole and vancomycin. However, recurrence and relapse of CDI, even after rounds of metronidazole/vancomycin administration is a problem that must be addressed. The efficacy of alternative antibiotics such as fidaxomicin, rifaximin, nitazoxanide, ramoplanin and tigecycline, as well as faecal microbiota transplantation has been assessed and some have yielded positive outcomes against C. difficile. Some bacteriocins have also shown promising effects against C. difficile in recent years. In light of this, the potential for emerging treatment options and efficacy of anti-C. difficile vaccines are discussed in this review.}, }
@article {pmid25561790, year = {2014}, author = {Gonçalves, Fda C and Schneider, N and Pinto, FO and Meyer, FS and Visioli, F and Pfaffenseller, B and Lopez, PL and Passos, EP and Cirne-Lima, EO and Meurer, L and Paz, AH}, title = {Intravenous vs intraperitoneal mesenchymal stem cells administration: what is the best route for treating experimental colitis?.}, journal = {World journal of gastroenterology}, volume = {20}, number = {48}, pages = {18228-18239}, pmid = {25561790}, issn = {2219-2840}, mesh = {Acute Disease ; Animals ; Apoptosis ; Biomarkers/blood ; Cells, Cultured ; Colitis/blood/chemically induced/pathology/physiopathology/*surgery ; Colon/metabolism/pathology/*physiopathology ; Cytokines/blood ; Dextran Sulfate ; Disease Models, Animal ; Inflammation Mediators/blood ; Infusions, Intravenous ; Infusions, Parenteral ; Male ; Mesenchymal Stem Cell Transplantation/*methods ; Mesenchymal Stem Cells/metabolism ; Mice, Inbred C57BL ; Phenotype ; *Regeneration ; T-Lymphocytes/metabolism/pathology ; Time Factors ; }, abstract = {AIM: To investigate the therapeutic effects of mesenchymal stem cells (MSCs) transplanted intraperitoneally and intravenously in a murine model of colitis.<br><br>METHODS: MSCs were isolated from C57BL/6 mouse adipose tissue. MSC cultures were analyzed according to morphology, cellular differentiation potential, and surface molecular markers. Experimental acute colitis was induced in C57BL/6 mice by oral administration of 2% dextran sulfate sodium (DSS) in drinking water ad libitum from days 0 to 7. Colitis mice were treated with 1 &#xd7; 10(6) MSCs via intraperitoneal or intravenous injection on days 2 and 5. The disease activity index was determined daily based on the following parameters: weight loss, stool consistency and presence of blood in the feces and anus. To compare morphological and functional differences in tissue regeneration between different MSC injection modalities, mice were euthanized on day 8, and their colons were examined for length, weight, and histopathological changes. Inflammatory responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 kit. Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling assay.<br><br>RESULTS: Intravenous infusion of MSCs was more effective than intraperitoneal treatment (P < 0.001) in reducing the clinical and histopathologic severity of colitis, which includes weight loss, diarrhea and inflammation. An histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory cells. This therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)]; and by the up-regulation of anti-inflammatory cytokines (IL-10 and IL-4). Intravenous transplantation also induced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs, which did not occur with intraperitoneal transplantation (P = 0.006). An increase in apoptotic T cells was observed after intravenous, but not intraperitoneal, MSC infusion, suggesting that MSCs can induce apoptosis in resistant T cells in colonic inflammation (P = 0.027).<br><br>CONCLUSION: Our results demonstrate that intravenous treatment is a superior method for reducing colon inflammation compared with intraperitoneal therapy.}, }
@article {pmid25561343, year = {2015}, author = {Cammarota, G and Ianiro, G and Cianci, R and Bibbò, S and Gasbarrini, A and Currò, D}, title = {The involvement of gut microbiota in inflammatory bowel disease pathogenesis: potential for therapy.}, journal = {Pharmacology &amp; therapeutics}, volume = {149}, number = {}, pages = {191-212}, doi = {10.1016/j.pharmthera.2014.12.006}, pmid = {25561343}, issn = {1879-016X}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; *Dietary Supplements ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects/immunology ; Humans ; Inflammatory Bowel Diseases/*diet therapy/*drug therapy/immunology ; Models, Immunological ; Prebiotics ; Probiotics/pharmacology/therapeutic use ; Synbiotics ; }, abstract = {Over the past recent years, a great number of studies have been directed toward the evaluation of the human host-gut microbiota interaction, with the goal to progress the understanding of the etiology of several complex diseases. Alterations in the intestinal microbiota associated with inflammatory bowel disease are well supported by literature data and have been widely accepted by the research community. The concomitant implementation of high-throughput sequencing techniques to analyze and characterize the composition of the intestinal microbiota has reinforced the view that inflammatory bowel disease results from altered interactions between gut microbes and the mucosal immune system and has raised the possibility that some form of modulation of the intestinal microbiota may constitute a potential therapeutic basis for the disease. The aim of this review is to describe the changes of gut microbiota in inflammatory bowel disease, focusing the attention on its involvement in the pathogenesis of the disease, and to review and discuss the therapeutic potential to modify the intestinal microbial population with antibiotics, probiotics, prebiotics, synbiotics and fecal microbiota transplantation.}, }
@article {pmid25553830, year = {2015}, author = {Xu, X and Zhang, X}, title = {Effects of cyclophosphamide on immune system and gut microbiota in mice.}, journal = {Microbiological research}, volume = {171}, number = {}, pages = {97-106}, doi = {10.1016/j.micres.2014.11.002}, pmid = {25553830}, issn = {1618-0623}, mesh = {Animals ; Biodiversity ; Cluster Analysis ; Cyclophosphamide/*pharmacology ; Cytokines/blood ; Immune System/*drug effects ; Immunity/drug effects ; Immunosuppressive Agents/*pharmacology ; Intestines/*drug effects/*microbiology ; Lymphocyte Activation/drug effects/immunology ; Lymphocyte Subsets/drug effects/immunology/metabolism ; Male ; Mice ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Cyclophosphamide (CP) is the most commonly used drug in autoimmune disease, cancer, blood and marrow transplantation. Recent data revealed that therapy efficacy of CP is gut microbiota-dependent. So, it is very important to understand how CP affects intestinal microbiota and immune function. In this study, the effects of CP on mice immuno-activity were firstly evaluated, then, the fecal microbiota from normal and CP-treated mice was compared, and the characteristic bacterial diversity and compositions were identified, using 454 pyrosequencing technology. The results showed that CP reduced the diversity and shifted the fecal microbiota composition. Specifically, CP treatment decreased the proportion of Bacteroidetes while increased the proportion of Firmictutes in the microbial community. Most importantly, specific microbiota signatures belonging to Bacteroides acidifaciens, Streptococcaceae and Alistipes were also identified, which would provide new insight into the efficacy and side effects in clinical usage of CP. This should be helpful for further demonstration of CP's action mechanism, development of personalized therapy strategies, and prediction of potential side effects related to various treatment regimens of CP.}, }
@article {pmid25550161, year = {2015}, author = {Gregory, JC and Buffa, JA and Org, E and Wang, Z and Levison, BS and Zhu, W and Wagner, MA and Bennett, BJ and Li, L and DiDonato, JA and Lusis, AJ and Hazen, SL}, title = {Transmission of atherosclerosis susceptibility with gut microbial transplantation.}, journal = {The Journal of biological chemistry}, volume = {290}, number = {9}, pages = {5647-5660}, pmid = {25550161}, issn = {1083-351X}, support = {HL28481/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; P01 HL028481/HL/NHLBI NIH HHS/United States ; P20 HL113452/HL/NHLBI NIH HHS/United States ; T32 GM088088/GM/NIGMS NIH HHS/United States ; UL1 TR000439/TR/NCATS NIH HHS/United States ; HL30568/HL/NHLBI NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; P01 HL030568/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Aorta/metabolism/pathology ; Atherosclerosis/blood/etiology/*microbiology ; Cecum/*microbiology ; Choline/administration &amp; dosage ; Diet/adverse effects ; Disease Susceptibility/blood/complications/*microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Host-Pathogen Interactions ; Humans ; Male ; Methylamines/blood/metabolism ; Mice, Inbred AKR ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Inbred DBA ; Mice, Inbred Strains ; Mice, Knockout ; Mice, Transgenic ; Microbiota/*physiology ; Species Specificity ; }, abstract = {Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n = 22 strains, r = 0.38; p = 0.0001). An atherosclerosis-prone and high TMAO-producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO-producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. Trimethylamine (TMA) and TMAO levels were initially higher in recipients on choline diet that received cecal microbes from C57BL/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden as compared with recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients and that tended to show coincident proportions with TMAO levels. Proportions of specific taxa were also identified that correlated with plasma TMAO levels in donors and recipients and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility.}, }
@article {pmid25549239, year = {2014}, author = {Allegretti, JR and Korzenik, JR and Hamilton, MJ}, title = {Fecal microbiota transplantation via colonoscopy for recurrent C. difficile Infection.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {94}, pages = {}, pmid = {25549239}, issn = {1940-087X}, support = {K08 DK094971/DK/NIDDK NIH HHS/United States ; T32 DK007533/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Colonoscopy/*methods ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult ; }, abstract = {Fecal Microbiota Transplantation (FMT) is a safe and highly effective treatment for recurrent and refractory C. difficile infection (CDI). Various methods of FMT administration have been reported in the literature including nasogastric tube, upper endoscopy, enema and colonoscopy. FMT via colonoscopy yields excellent cure rates and is also well tolerated. We have found that patients find this an acceptable and tolerable mode of delivery. At our Center, we have initiated a fecal transplant program for patients with recurrent or refractory CDI. We have developed a protocol using an iterative process of revision and have performed 24 fecal transplants on 22 patients with success rates comparable to the current published literature. A systematic approach to patient and donor screening, preparation of stool, and delivery of the stool maximizes therapeutic success. Here we detail each step of the FMT protocol that can be carried out at any endoscopy center with a high degree of safety and success.}, }
@article {pmid25548572, year = {2014}, author = {Satokari, R and Fuentes, S and Mattila, E and Jalanka, J and de Vos, WM and Arkkila, P}, title = {Fecal transplantation treatment of antibiotic-induced, noninfectious colitis and long-term microbiota follow-up.}, journal = {Case reports in medicine}, volume = {2014}, number = {}, pages = {913867}, pmid = {25548572}, issn = {1687-9627}, abstract = {Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) and is considered as a treatment for other gastrointestinal (GI) diseases. We followed up the relief of symptoms and long-term, over-a-year microbiota stabilization in a 46-year-old man, who underwent FMT for antibiotic-induced, non-CDI colitis nine months after being treated for CDI by FMT. Fecal and mucosal microbiota was analyzed before the second FMT and during 14 months after FMT by using a high-throughput phylogenetic microarray. FMT resolved the symptoms and restored normal GI-function. Microbiota analysis revealed increased bacterial diversity in the rectal mucosa and a stable fecal microbiota up to three months after FMT. A number of mucosa-associated bacteria increased after FMT and some of these bacteria remained increased in feces up to 14 months. Notably, the increased bacteria included Bifidobacterium spp. and various representatives of Clostridium clusters IV and XIVa, such as Clostridium leptum, Oscillospira guillermondii, Sporobacter termitidis, Anaerotruncus colihominis, Ruminococcus callidus, R. bromii, Lachnospira pectinoschiza, and C. colinum, which are presumed to be anti-inflammatory. The presented case suggests a possible role of microbiota in restoring and maintaining normal GI-functionality and improves our knowledge on the etiology of antibiotic-induced, noninfectious colitis.}, }
@article {pmid25548472, year = {2014}, author = {Han, JL and Lin, HL}, title = {Intestinal microbiota and type 2 diabetes: from mechanism insights to therapeutic perspective.}, journal = {World journal of gastroenterology}, volume = {20}, number = {47}, pages = {17737-17745}, pmid = {25548472}, issn = {2219-2840}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bacteria/classification/drug effects/*growth &amp; development ; Bile Acids and Salts/metabolism ; Body Weight ; Diabetes Mellitus, Type 2/metabolism/*microbiology/physiopathology/therapy ; Gastrointestinal Hormones/metabolism ; Host-Pathogen Interactions ; Humans ; Insulin/metabolism ; Insulin Resistance ; Intestinal Mucosa/metabolism ; Intestines/*microbiology/physiopathology ; *Microbiota ; Non-alcoholic Fatty Liver Disease/metabolism/microbiology ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {The incidence of type 2 diabetes (T2DM) is rapidly increasing worldwide. However, the pathogenesis of T2DM has not yet been well explained. Recent evidence suggests that the intestinal microbiota composition is associated with obesity and T2DM. In this review, we provide an overview about the mechanisms underlying the role of intestinal microbiota in the pathogenesis of T2DM. There is clear evidence that the intestinal microbiota influences the host through its effect on body weight, bile acid metabolism, proinflammatory activity and insulin resistance, and modulation of gut hormones. Modulating gut microbiota with the use of probiotics, prebiotics, antibiotics, and fecal microbiota transplantation may have benefits for improvement in glucose metabolism and insulin resistance in the host. Further studies are required to increase our understanding of the complex interplay between intestinal microbiota and the host with T2DM. Further studies may be able to boost the development of new effective therapeutic approaches for T2DM.}, }
@article {pmid25547668, year = {2015}, author = {Fernández Caamaño, B and Quiles Blanco, MJ and Fernández Tomé, L and Burgos Lizáldez, E and Sarría Osés, J and Molina Arias, M and Prieto Bozano, G}, title = {[Intestinal failure and transplantation in microvillous inclusion disease].}, journal = {Anales de pediatria (Barcelona, Spain : 2003)}, volume = {83}, number = {3}, pages = {160-165}, doi = {10.1016/j.anpedi.2014.11.013}, pmid = {25547668}, issn = {1695-9531}, mesh = {Female ; Humans ; Infant, Newborn ; Intestinal Diseases/etiology ; Intestines/*transplantation ; Malabsorption Syndromes/*complications/*surgery ; Male ; Microvilli/*pathology ; Mucolipidoses/*complications/*surgery ; Parenteral Nutrition ; Retrospective Studies ; }, abstract = {INTRODUCTION: Microvillous inclusion disease is a rare autosomal recessive condition, characterized by severe secretory diarrhea that produces a permanent intestinal failure and dependency on parenteral nutrition. It usually begins in the neonatal period, and the only treatment at present is intestinal transplantation.<br><br>PATIENTS AND METHODS: A retrospective review was conducted on 6 patients (three males and three females) diagnosed with microvillous inclusion disease between 1998 and 2013.<br><br>RESULTS: All debuted in the first month of life, with a median age of three days (range, 3-30 days), and had secretory diarrhea dependent on parenteral nutrition, with fasting fecal volume of 150-200ml/kg/day. Light microscopy of duodenal biopsy samples showed varying degrees of villous atrophy without cryptic hyperplasia, accumulation of PAS positive material in the cytoplasm of enterocytes brush border, and anti-CD10 immunostaining was suggestive of intracytoplasmic inclusions. Diagnostic confirmation was performed with electron microscopy. Two of them had a genetic study, and showed mutations in MYO5B gene. Three died and three are alive; two of them with an intestinal transplantation and the third waiting for a multivisceral transplantation.}, }
@article {pmid25546740, year = {2015}, author = {Nesher, L and Rolston, KV and Shah, DP and Tarrand, JT and Mulanovich, V and Ariza-Heredia, EJ and Chemaly, RF}, title = {Fecal colonization and infection with Pseudomonas aeruginosa in recipients of allogeneic hematopoietic stem cell transplantation.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {17}, number = {1}, pages = {33-38}, doi = {10.1111/tid.12323}, pmid = {25546740}, issn = {1399-3062}, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Drug Resistance, Multiple, Bacterial ; Feces/microbiology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Infection Control ; Male ; Middle Aged ; Pseudomonas Infections/*epidemiology/microbiology ; Pseudomonas aeruginosa/*isolation &amp; purification ; Retrospective Studies ; Sentinel Surveillance ; Texas/epidemiology ; Transplantation, Homologous ; Young Adult ; }, abstract = {BACKGROUND: Pseudomonas aeruginosa, especially multidrug-resistant (MDR) isolates, is an important pathogen in allogeneic hematopoietic stem cell transplant (HCT) recipients. The ability to identify patients at risk for these infections and administer appropriate empiric therapy, particularly during episodes of neutropenia, may improve outcomes and also direct infection control and antimicrobial stewardship efforts. Many transplant centers obtain routine surveillance stool cultures (SSCs) from HCT recipients to test for colonization with vancomycin-resistant enterococci, and extended-spectrum beta lactamase-producing Enterobacteriaceae. Our center initiated the performance of SSCs for P. aeruginosa, because of a perceived increase in the frequency of infection with MDR strains. The aim of this study was to determine the utility of this practice.<br><br>METHODS: We conducted a 2-year (2010-2011) retrospective review of the medical records of all patients who underwent allogeneic HCT at our cancer center to (a) determine the frequency of fecal colonization with P.&#xa0;aeruginosa, including MDR strains; (b) to determine the overall frequency of subsequent P.&#xa0;aeruginosa infection, as well as the frequency of infection with MDR strains; (c) to ascertain the proportion of subsequent infections likely arising from the intestinal tract; and (d) to determine risk factors for progression from colonization to infection.<br><br>RESULTS: Of 794 study patients, 58 (7.3%) had at least 1 positive SSC for P.&#xa0;aeruginosa; 19/58 (32.8%) developed a subsequent pseudomonal infection (11 with matching antimicrobial resistance patterns). On the other hand, 37/736 (5%) of the patients who were not colonized, developed a pseudomonal infection. The type of infection observed was pneumonia in 26 (46%) patients, bloodstream infection in 20 (36%), urinary tract infection in 8 (14%), and infections at other sites in 2 (4%). The incidence of MDR P.&#xa0;aeruginosa in the entire cohort was 2.2% (18 of 794): 12 had positive SSCs and 7 of these patients later developed MDR P.&#xa0;aeruginosa infections. Patients with acute myelogenous leukemia were more likely to be colonized and to develop subsequent infection. No infection-related deaths were observed during the first 30&#xa0;days after infection.<br><br>CONCLUSIONS: The incidence of P.&#xa0;aeruginosa colonization and subsequent infection was low. Patients who were not colonized had a low chance of developing P.&#xa0;aeruginosa infection. Most patients who developed infection did not have fecal colonization, suggesting a different source of infection. SSCs for P.&#xa0;aeruginosa provide incomplete information regarding the source of infection.}, }
@article {pmid25546336, year = {2015}, author = {Lynch, SV}, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in Pediatric Patients: Encouragement Wrapped in Caution.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {60}, number = {1}, pages = {1-3}, doi = {10.1097/MPG.0000000000000612}, pmid = {25546336}, issn = {1536-4801}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/*therapy ; Female ; Humans ; Male ; *Microbiota ; *Therapies, Investigational ; }, }
@article {pmid25538312, year = {2015}, author = {Hartstra, AV and Bouter, KE and Bäckhed, F and Nieuwdorp, M}, title = {Insights into the role of the microbiome in obesity and type 2 diabetes.}, journal = {Diabetes care}, volume = {38}, number = {1}, pages = {159-165}, doi = {10.2337/dc14-0769}, pmid = {25538312}, issn = {1935-5548}, mesh = {Diabetes Mellitus, Type 2/*microbiology ; Diet ; Endotoxemia/prevention &amp; control ; Feces/microbiology ; *Feeding Behavior ; Female ; Humans ; Insulin Resistance ; Intestines/microbiology ; Male ; Metabolic Syndrome/metabolism/microbiology ; *Microbiota ; Obesity/metabolism/*microbiology ; Randomized Controlled Trials as Topic ; }, abstract = {The worldwide prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise at an alarming pace. Recently the potential role of the gut microbiome in these metabolic disorders has been identified. Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome seems to be more efficient in harvesting energy from the diet. Lean male donor fecal microbiota transplantation (FMT) in males with metabolic syndrome resulted in a significant improvement in insulin sensitivity in conjunction with an increased intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains. Such differences in gut microbiota composition might function as early diagnostic markers for the development of T2DM in high-risk patients. Products of intestinal microbes such as butyrate may induce beneficial metabolic effects through enhancement of mitochondrial activity, prevention of metabolic endotoxemia, and activation of intestinal gluconeogenesis via different routes of gene expression and hormone regulation. Future research should focus on whether bacterial products (like butyrate) have the same effects as the intestinal bacteria that produce it, in order to ultimately pave the way for more successful interventions for obesity and T2DM. The rapid development of the currently available techniques, including use of fecal transplantations, has already shown promising results, so there is hope for novel therapies based on the microbiota in the future.}, }
@article {pmid25533663, year = {2015}, author = {Song, Y and Xu, C and Shao, S and Liu, J and Xing, W and Xu, J and Qin, C and Li, C and Hu, B and Yi, S and Xia, X and Zhang, H and Zhang, X and Wang, T and Pan, W and Yu, C and Wang, Q and Lin, X and Wang, L and Gao, L and Zhao, J}, title = {Thyroid-stimulating hormone regulates hepatic bile acid homeostasis via SREBP-2/HNF-4α/CYP7A1 axis.}, journal = {Journal of hepatology}, volume = {62}, number = {5}, pages = {1171-1179}, doi = {10.1016/j.jhep.2014.12.006}, pmid = {25533663}, issn = {1600-0641}, mesh = {Animals ; *Bile Acids and Salts/biosynthesis/metabolism ; Cholesterol 7-alpha-Hydroxylase/*metabolism ; Healthy Volunteers ; Hepatocyte Nuclear Factor 4/*metabolism ; Homeostasis/physiology ; Humans ; Liver/*metabolism ; Mice ; Mice, Inbred C57BL ; Models, Theoretical ; Rats ; Signal Transduction/physiology ; Sterol Regulatory Element Binding Protein 2/*metabolism ; Thyrotropin/*metabolism ; }, abstract = {BACKGROUND &amp; AIMS: Bile acids (BAs) play a crucial role in dietary fat digestion and in the regulation of lipid, glucose, and energy metabolism. Thyroid-stimulating hormone (TSH) is a hormone produced by the anterior pituitary gland that directly regulates several metabolic pathways. However, the impact of TSH on BA homeostasis remains largely unknown.<br><br>METHODS: We analyzed serum BA and TSH levels in healthy volunteers under strict control of caloric intake. Thyroidectomized rats were administered thyroxine and injected with different doses of TSH. Tshr(-/-) mice were supplemented with thyroxine, and C57BL/6 mice were injected with Tshr-siRNA via the tail vein. The serum BA levels, BA pool size, and fecal BA excretion rate were measured. The regulation of SREBP-2, HNF-4&#x3b1;, and CYP7A1 by TSH were analyzed using luciferase reporter, RNAi, EMSA, and CHIP assays.<br><br>RESULTS: A negative correlation was observed between the serum levels of TSH and the serum BA levels in healthy volunteers. TSH administration led to a decrease in BA content and CYP7A1 activity in thyroidectomized rats supplemented with thyroxine. When Tshr was silenced in mice, the BA pool size, fecal BA excretion rate, and serum BA levels all increased. Additionally, we found that HNF-4&#x3b1; acts as a critical molecule through which TSH represses CYP7A1 activity. We further confirmed that the accumulation of mature SREBP-2 protein could impair the capacity of nuclear HNF-4&#x3b1; to bind to the CYP7A1 promoter, a mechanism that appears to mediate the effects of TSH.<br><br>CONCLUSIONS: TSH represses hepatic BA synthesis via a SREBP-2/HNF-4&#x3b1;/CYP7A1 signaling pathway. This finding strongly supports the notion that TSH is an important pathophysiological regulator of liver BA homeostasis independently of thyroid hormones.}, }
@article {pmid25531993, year = {2014}, author = {Ierardi, E and Giangaspero, A and Losurdo, G and Giorgio, F and Amoruso, A and De Francesco, V and Di Leo, A and Principi, M}, title = {Quadruple rescue therapy after first and second line failure for Helicobacter pylori treatment: comparison between two tetracycline-based regimens.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {23}, number = {4}, pages = {367-370}, doi = {10.15403/jgld.2014.1121.234.qrth}, pmid = {25531993}, issn = {1842-1121}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*administration &amp; dosage/adverse effects ; Breath Tests ; Drug Resistance, Bacterial ; Drug Therapy, Combination ; Endoscopy, Gastrointestinal ; Feces/microbiology ; Female ; Helicobacter Infections/diagnosis/*drug therapy/microbiology ; Helicobacter pylori/*drug effects/pathogenicity ; Humans ; Italy ; Male ; Middle Aged ; Minocycline/*administration &amp; dosage/adverse effects ; Organometallic Compounds/administration &amp; dosage ; Proton Pump Inhibitors/administration &amp; dosage ; Rabeprazole/administration &amp; dosage ; Rifabutin/administration &amp; dosage ; Time Factors ; Tinidazole/administration &amp; dosage ; Treatment Failure ; Young Adult ; }, abstract = {BACKGROUND AND AIMS: Antibiotic resistance is the main reason for failure of Helicobacter pylori (H. pylori) treatment. Currently, guidelines recommend a treatment guided by antimicrobial susceptibility testing after two failures. However, microbial culture is not feasible everywhere, and the limited number of effective antibiotics against the bacterium narrows the options; thus a rescue therapy combining antibiotics with a low resistance may be fitting.<br><br>METHODS: Patients who have failed a first-line treatment (either prolonged triple or sequential regimens) and, successively, a levofloxacin-based triple therapy were considered for the study. Subjects underwent urea breath test (UBT), stool antigen test (ST) and endoscopy/histology to confirm the diagnosis. Cytopenia and impaired liver and kidney function were exclusion criteria. Fifty-four subjects were randomized 1:1 to two regimens: RMB Rabeprazole/Rifabutin/Minocycline/Bismuth sub-citrate or MTB Rabeprazole/Tinidazole/Minocycline/Bismuth sub-citrate both for 10 days. The results were checked 6 weeks after the end of therapy with ST/UBT plus endoscopy when indicated.<br><br>RESULTS: RMB eradicated the bacterium in 21 patients. Two subjects dropped out. The eradication rate was 77.7% (CI 62.0-93.4%) at intention-to-treat and 84.0% (CI 69.6-98.4%) at per-protocol analysis. MTB was successful in 14 patients (51.9%, CI 33.1-70.7%). No patient withdrew from the treatment for adverse events. Drug-related side effects were reported only in 3 subjects, but in all cases the treatment was carried on.<br><br>CONCLUSIONS: The association minocycline/rifabutin seems to have a synergic effect and a good therapeutic outcome in patients who have failed at least two previous regimens, although a trial on a large population is needed.}, }
@article {pmid25531348, year = {2014}, author = {Sokol, H}, title = {Probiotics and antibiotics in IBD.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {32 Suppl 1}, number = {}, pages = {10-17}, doi = {10.1159/000367820}, pmid = {25531348}, issn = {1421-9875}, mesh = {Anti-Bacterial Agents/pharmacology/*therapeutic use ; Crohn Disease/drug therapy/microbiology ; Gastrointestinal Tract/drug effects/microbiology/pathology ; Humans ; Inflammatory Bowel Diseases/*drug therapy/microbiology ; Microbiota/drug effects ; Probiotics/pharmacology/*therapeutic use ; }, abstract = {The involvement of the gut microbiota in the pathogenesis of IBD is supported by many findings and is thus now commonly acknowledged. The imbalance in the composition of the microbiota (dysbiosis) observed in IBD patients is one of the strongest arguments and provides the rationale for a therapeutic manipulation of the gut microbiota. The tools available to achieve this goal include fecal microbiota transplantation, but antibiotics and probiotics have been the most used one until now. Although antibiotics have shown some efficacy in inducing remission in Crohn's disease (CD) and ulcerative colitis (UC), as well as preventing postoperative relapse in CD, they are not currently recommended for the treatment of IBD except for septic complications, notably because of long-term tolerance and ecological issues. Some probiotics have been shown to be as good as 5-aminosalicylic acid to maintain remission in mild-to-moderate UC, but have been disappointing until now in CD in all tested indications. In pouchitis, antibiotics and probiotics have shown efficacy for inducing and maintaining remission, respectively. Targeting the gut microbiota in IBD is an attractive strategy. Current efforts to better understand the host-microbiota interactions in physiological as well as disease settings might lead to the development of rational-based treatments.}, }
@article {pmid25528828, year = {2014}, author = {Privalov, MA and Sizenko, AK}, title = {[Fecal microbiota transplantation in treatment of inflammatory bowel diseases].}, journal = {Likars'ka sprava}, volume = {}, number = {11}, pages = {15-21}, pmid = {25528828}, issn = {1019-5297}, mesh = {Administration, Rectal ; Enema ; Feces/microbiology ; Gastrointestinal Tract/*microbiology/pathology ; Humans ; Inflammatory Bowel Diseases/*microbiology/pathology/*therapy ; Microbial Consortia/physiology ; Microbiota/*physiology ; Probiotics/*administration &amp; dosage ; Quality of Life ; Symbiosis/physiology ; }, abstract = {Inflammatory bowel diseases (IBD) are chronic, recurrent disease associated with significant morbidity and disability rates and marked reduction of quality of life. The exact aetiology of these conditions is unknown, however, there is increasing data supporting the influence of gut microbiota in the pathogenesis of IBD. Despite of large number of actively exploring approaches to IBD treatment, some patients remain refractory to standard management or have significant adverse side effects. Given the probably role of the gastrointestinal microbiotain development of IBD, treatments that manipulate the microbiota have been investigated with varying degree of efficacy. Faecal microbiota transplantation (FMT) can be considered as alternative regimen for IBD management, but there is currently a lack of evidence supporting this approach in similar conditions. The comprehensive data are necessary to provide understandable and clear conclusion to guide current practice and future research.}, }
@article {pmid25525379, year = {2014}, author = {Ghouri, YA and Richards, DM and Rahimi, EF and Krill, JT and Jelinek, KA and DuPont, AW}, title = {Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease.}, journal = {Clinical and experimental gastroenterology}, volume = {7}, number = {}, pages = {473-487}, pmid = {25525379}, issn = {1178-7023}, abstract = {BACKGROUND: Probiotics are microorganisms that are ingested either in combination or as a single organism in an effort to normalize intestinal microbiota and potentially improve intestinal barrier function. Recent evidence has suggested that inflammatory bowel disease (IBD) may result from an inappropriate immunologic response to intestinal bacteria and a disruption in the balance of the gastrointestinal microbiota in genetically susceptible individuals. Prebiotics, synbiotics, and probiotics have all been studied with growing interest as adjuncts to standard therapies for IBD. In general, probiotics have been shown to be well-tolerated with few side effects, making them a potential attractive treatment option in the management of IBD.<br><br>AIM: To perform a systematic review of randomized controlled trials on the use of probiotics, prebiotics, and synbiotics in IBD.<br><br>RESULTS: In our systematic review we found 14 studies in patients with Crohn's disease (CD), 21 studies in patients with ulcerative colitis (UC), and five studies in patients with pouchitis. These were randomized controlled trials using probiotics, prebiotics, and/or synbiotics. In patients with CD, multiple studies comparing probiotics and placebo showed no significant difference in clinical outcomes. Adding a probiotic to conventional treatment improved the overall induction of remission rates among patients with UC. There was also a similar benefit in maintaining remission in UC. Probiotics have also shown some efficacy in the treatment of pouchitis after antibiotic-induced remission.<br><br>CONCLUSIONS: To date, there is insufficient data to recommend probiotics for use in CD. There is evidence to support the use of probiotics for induction and maintenance of remission in UC and pouchitis. Future quality studies are needed to confirm whether probiotics, prebiotics, and synbiotics have a definite role in induction or maintenance of remission in CD, UC, and pouchitis. Similar to probiotics, fecal microbiota transplantation provides an alternate modality of therapy to treat IBD by influencing the intestinal flora.}, }
@article {pmid25520950, year = {2014}, author = {Urdaneta-Morales, S}, title = {Chagas' disease: an emergent urban zoonosis. The caracas valley (Venezuela) as an epidemiological model.}, journal = {Frontiers in public health}, volume = {2}, number = {}, pages = {265}, pmid = {25520950}, issn = {2296-2565}, abstract = {The unprecedented emergence of important public health and veterinary zoonoses is usually a result of exponential population growth and globalization of human activities. I characterized Chagas' disease as an emergent zoonosis in the Caracas Valley (Venezuela) due to the following findings: the presence of reservoirs (Didelphis marsupialis, Rattus rattus) and vectors (Panstrongylus geniculatus, Panstrongylus rufotuberculatus) infected with Trypanosoma cruzi in urbanized or marginalized areas; the elevated contact between P. geniculatus and human beings detected by parasitological and molecular examinations of triatomine feces demonstrated the possibility of transmission risks; a study of outbreaks of urban Chagas' disease reported the first proven case of oral transmission of T. cruzi to human beings; the risk of transmission of glandular metacyclic stages from marsupials by experimental ocular and oral instillation; mice genitalia infected with T. cruzi contaminated blood resulted in the formation of amastigotes very close to the lumen suggesting that there may be a possibility of infection via their release into the urine and thence to the exterior; the ubiquitous histotropism and histopathology of T. cruzi was demonstrated using a mouse model; the presence of experimental T. cruzi pseudocysts in adipose, bone-cartilage, and eye tissue indicated a potential risk for transplants. Socio-sanitary programs that include improvements in housing, vector control, and access to medical treatment, as well as strategies aimed at combating social inequalities, poverty, and underdevelopment should be undertaken in those areas where zoonoses are most prevalent. Disciplines, such as Ecology, Epidemiology, Medical Entomology, Human and Veterinary Medicine, Environmental Studies, Public Health, Social and Political Studies, Immunology, Microbiology, and Pharmacology could all provide important contributions that aim to reduce the occurrence of factors governing the spread of emergent diseases.}, }
@article {pmid25505015, year = {2014}, author = {}, title = {Faecal microbiota transplantation.}, journal = {Drug and therapeutics bulletin}, volume = {52}, number = {12}, pages = {141-144}, doi = {10.1136/dtb.2014.12.0298}, pmid = {25505015}, issn = {1755-5248}, mesh = {Biological Therapy/adverse effects/*methods ; Clostridium Infections/*therapy ; Feces/*microbiology ; Guidelines as Topic ; Humans ; Inflammatory Bowel Diseases/*therapy ; *Microbiota ; Patient Acceptance of Health Care ; Transplantation/adverse effects/*methods ; }, abstract = {The use of faeces for the treatment of gastrointestinal diseases was described in 4th century Chinese medicine for the treatment of severe diarrhoea.1 More recently there has been renewed interest in this unconventional biological therapy, particularly for the treatment of recurrent Clostridium difficile infection (CDI) and to a lesser extent inflammatory bowel diseases (IBD). Faecal microbiota transplantation† (FMT) involves the introduction of enteric bacteria from the faeces of healthy donors in order to restore a healthy balance of bacteria in the gut.2 In March 2014, the National Institute for Health and Care Excellence (NICE) issued guidance on the use of FMT for the treatment of recurrent CDI that has failed to respond to antibiotics and other treatments.2 Here we review the use of FMT in CDI and IBD.}, }
@article {pmid25500625, year = {2014}, author = {Matsuoka, K and Mizuno, S and Hayashi, A and Hisamatsu, T and Naganuma, M and Kanai, T}, title = {Fecal microbiota transplantation for gastrointestinal diseases.}, journal = {The Keio journal of medicine}, volume = {63}, number = {4}, pages = {69-74}, doi = {10.2302/kjm.2014-0006-RE}, pmid = {25500625}, issn = {1880-1293}, mesh = {Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; *Microbiota ; Randomized Controlled Trials as Topic ; }, abstract = {Fecal microbiota transplantation (FMT) is a treatment to restore the normal microbial composition of the gut by introducing fecal microbiota obtained from a healthy donor into a diseased individual. There has been a growing interest in the use of FMT as a treatment of various diseases including Clostridium difficile infection (CDI), inflammatory bowel disease, and irritable bowel syndrome. Despite the increasing application of FMT, there are no standard protocols. Many aspects of FMT procedures vary regarding donor selection, preparation of fecal materials, recipient preparation, and route of administration. FMT is most successful in treating recurrent CDI. A randomized controlled trial reported a success rate of approximaetly 90%. Ulcerative colitis (UC) is a potentially good indication for FMT, although limited evidence is available on the use of FMT for the treatment of UC. Only several small case series have been reported, and the results in terms of efficacy are inconsistent. FMT can also be used to treat diseases other than gastrointestinal disorders in which the gut microbiota is disturbed, e.g., cardiovascular diseases, autoimmune diseases, and metabolic disorders. There remain many unanswered questions with regard to FMT, and more research is required in this field.}, }
@article {pmid25492317, year = {2014}, author = {Valeur, J and Midtvedt, T}, title = {Faeces transplantation—new wonder medicine?.}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {134}, number = {23-24}, pages = {2233}, doi = {10.4045/tidsskr.14.1261}, pmid = {25492317}, issn = {0807-7096}, mesh = {Biological Therapy/*methods ; Feces/*microbiology ; Humans ; Microbiota ; Transplantation/*methods ; }, }
@article {pmid25489701, year = {2015}, author = {Hikosaka, M and Yazawa, M and Sakuma, H and Uchikawa, Y and Takayama, M and Kishi, K}, title = {Anatomic basis of anorectal reconstruction by dynamic graciloplasty with pudendal nerve anastomosis.}, journal = {Diseases of the colon and rectum}, volume = {58}, number = {1}, pages = {104-108}, doi = {10.1097/DCR.0000000000000268}, pmid = {25489701}, issn = {1530-0358}, mesh = {Anal Canal/anatomy &amp; histology/*innervation/*surgery ; Anastomosis, Surgical ; Cadaver ; Humans ; Lumbosacral Plexus/anatomy &amp; histology/*surgery ; Muscle, Skeletal/anatomy &amp; histology/*innervation/*transplantation ; Pudendal Nerve/anatomy &amp; histology/*surgery ; Retrospective Studies ; Surgical Flaps ; }, abstract = {BACKGROUND: Dynamic graciloplasty has been proposed for anal reconstruction, but this method has 2 major drawbacks. First, an electrical device is required for control of the gracilis. The anastomosis with the pudendal nerve will provide more physiological control. Second, the limitation in the mobility of the muscle flap results in wrapping the anal canal with the muscle's distal portion, which is tendonlike and inelastic. Enhancing the mobility of the muscle flap will enable wrapping with the proximal, muscle-like, and extensible portion, possibly providing better sphincteric function. However, the basis for such an operative method is lacking.<br><br>OBJECTIVE: The aim of this study is to provide the basis for the refined method of anal sphincter reconstruction by dynamic graciloplasty with pudendal nerve anastomosis and to verify the feasibility of lengthening the nerve to the gracilis muscle flap by dissecting into the muscle belly, detaching the gracilis muscle from its origin, and enhancing the mobility of the muscle flap.<br><br>STUDY DESIGN: This is a retrospective, descriptive study.<br><br>METHODS: The results from the anatomical study on 9 cadavers are reported.<br><br>RESULTS: Tension-free anastomosis of the pudendal nerve and nerve to the gracilis was successfully performed in all the 9 cases: in 2 cases, by lengthening the nerve. The detachment of the muscle origin improved the mobility of the muscle flap, and the more proximal portion could be used for wrapping the anal canal, as confirmed in 4 cases.<br><br>LIMITATIONS: The limited number of cases was a shortcoming of this study.<br><br>CONCLUSIONS: By lengthening the nerve to the muscle, the gracilis can be used for anal sphincter reconstruction with pudendal nerve anastomosis, negating the need for an electrical device. By detaching the origin of the gracilis muscle, its proximal portion can be used to wrap the anal canal, possibly enabling a longer functional canal with stronger constricting force and better vascularity. These modifications to past methods may improve fecal continence after the operation.}, }
@article {pmid25487858, year = {2015}, author = {Göttgens, KW and Smeets, RR and Stassen, LP and Beets, G and Breukink, SO}, title = {Systematic review and meta-analysis of surgical interventions for high cryptoglandular perianal fistula.}, journal = {International journal of colorectal disease}, volume = {30}, number = {5}, pages = {583-593}, pmid = {25487858}, issn = {1432-1262}, mesh = {Bioprosthesis ; Case-Control Studies ; Fecal Incontinence/prevention &amp; control ; Female ; Fibrin Tissue Adhesive/*pharmacology ; Humans ; Ligation/methods ; Male ; Prognosis ; Randomized Controlled Trials as Topic ; Rectal Fistula/*pathology/*surgery ; Recurrence ; Risk Assessment ; Stem Cell Transplantation/*methods ; *Surgical Flaps ; Treatment Outcome ; Video-Assisted Surgery ; Wound Healing/physiology ; }, abstract = {PURPOSE: Perianal fistulas, and specifically high perianal fistulas, remain a surgical treatment challenge. Many techniques have, and still are, being developed to improve outcome after surgery. A systematic review and meta-analysis was performed for surgical treatments for high cryptoglandular perianal fistulas.<br><br>METHODS: Medline (Pubmed, Ovid), Embase and The Cochrane Library databases were searched for relevant randomized controlled trials on surgical treatments for high cryptoglandular perianal fistulas. Two independent reviewers selected articles for inclusion based on title, abstract and outcomes described. The main outcome measurement was the recurrence/healing rate. Secondary outcomes were continence status, quality of life and complications.<br><br>RESULTS: The number of randomized trials available was low. Fourteen studies could be included in the review. A meta-analysis could only be performed for the mucosa advancement flap versus the fistula plug, and did not show a result in favour of either technique in recurrence or complication rate. The mucosa advancement flap was the most investigated technique, but did not show an advantage over any other technique. Other techniques identified in randomized studies were seton treatment, medicated seton treatment, fibrin glue, autologous stem cells, island flap anoplasty, rectal wall advancement flap, ligation of intersphincteric fistula tract, sphincter reconstruction, sphincter-preserving seton and techniques combined with antibiotics. None of these techniques seem superior to each other.<br><br>CONCLUSIONS: The best surgical treatment for high cryptoglandular perianal fistulas could not be identified. More randomized controlled trials are needed to find the best treatment. The mucosa advancement flap is the most investigated technique available.}, }
@article {pmid25474284, year = {2014}, author = {Kump, PK and Krause, R and Steininger, C and Gröchenig, HP and Moschen, A and Madl, C and Novacek, G and Allerberger, F and Högenauer, C}, title = {[Recommendations for the use of faecal microbiota transplantation "stool transplantation": consensus of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) in cooperation with the Austrian Society of Infectious Diseases and Tropical Medicine].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {52}, number = {12}, pages = {1485-1492}, doi = {10.1055/s-0034-1385562}, pmid = {25474284}, issn = {1439-7803}, mesh = {Austria ; Biological Therapy/methods ; Feces/*microbiology ; Gastroenterology/*standards ; Humans ; Inflammatory Bowel Diseases/*microbiology/*therapy ; *Microbiota ; *Practice Guidelines as Topic ; Transplantation, Homologous/methods ; }, abstract = {The intestinal microbiota has a pivotal role in the maintenance of health of the human organism, especially in the defense against pathogenic microorganisms. Alterations in the microbiota, also termed dysbiosis, seem to be involved in the pathogenesis of a variety of intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT), also known as stool transplantation, is a therapeutic procedure aiming at restoring an altered intestinal microbiota by administration of stool microorganisms from a healthy donor into the intestinal tract of a patient. FMT is most commonly used for recurrent forms of Clostridium difficile infections (CDI). There are currently many cohort studies in a large number of patients and a randomized controlled trial showing a dramatic effect of FMT for this indication. Therefore FMT is recommended by international medical societies for the treatment of recurrent CDI with high scientific evidence. Other potential indications are the treatment of fulminant CDI or the treatment of inflammatory bowel diseases. In the practical utilization of FMT there are currently several open questions regarding the screening of stool donors, the processing of stool and the mode of FMT application. Different modes of FMT application have been described, the application into the colon has to be preferred due to less reported side effects than the application into the upper gastrointestinal tract. So far only very few side effects due to FMT have been reported, nevertheless the use and risks of FMT are currently intensely debated in the medical community. This consensus report of the Austrian society of gastroenterology and hepatology (ÖGGH) in cooperation with the Austrian society of infectious diseases and tropical medicine provides instructions for physicians who want to use FMT which are based on the current medical literature.}, }
@article {pmid25473198, year = {2014}, author = {Dai, YX and Shi, CB and Cui, BT and Wang, M and Ji, GZ and Zhang, FM}, title = {Fecal microbiota transplantation and prednisone for severe eosinophilic gastroenteritis.}, journal = {World journal of gastroenterology}, volume = {20}, number = {43}, pages = {16368-16371}, pmid = {25473198}, issn = {2219-2840}, mesh = {Adult ; Biological Therapy/*methods ; Biopsy ; Colonoscopy ; Contrast Media ; *Diagnostic Errors ; Enteritis/complications/diagnosis/microbiology/*therapy ; Eosinophilia/complications/diagnosis/microbiology/*therapy ; Feces/*microbiology ; Gastritis/complications/diagnosis/microbiology/*therapy ; Glucocorticoids/*therapeutic use ; Humans ; Male ; Predictive Value of Tests ; Prednisone/*therapeutic use ; Treatment Outcome ; }, abstract = {Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations. We describe a case of severe eosinophilic gastroenteritis presenting as frequent bowel obstruction and diarrhea in a 35-year-old man. The patient was misdiagnosed and underwent surgery because of intestinal obstruction when he was first admitted to a local hospital. Then he was misdiagnosed as having Crohn's disease in another university teaching hospital. Finally, the patient asked for further treatment from our hospital because of the on-going clinical trial for treating refractory Crohn's disease by fecal microbiota transplantation. Physical examination revealed a slight distended abdomen with diffuse tenderness. Laboratory investigation showed the total number of normal leukocytes with neutrophilia as 90.5%, as well as eosinopenia, monocytopenia and lymphocytopenia. Barium radiography and sigmoidoscopy confirmed inflammatory stenosis of the sigmoid colon. We diagnosed the patient as having eosinophilic gastroenteritis by multi-examinations. The patient was treated by fecal microbiota transplantation combined with oral prednisone, and was free from gastrointestinal symptoms at the time when we reported his disease. This case highlights the importance of awareness of manifestations of a rare disease like eosinophilic gastroenteritis.}, }
@article {pmid25470590, year = {2014}, author = {Mandalia, A and Kraft, CS and Dhere, T}, title = {Diverticulitis after fecal microbiota transplant for C. difficile infection.}, journal = {The American journal of gastroenterology}, volume = {109}, number = {12}, pages = {1956-1957}, pmid = {25470590}, issn = {1572-0241}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; Colon, Sigmoid/diagnostic imaging ; Diverticulitis, Colonic/diagnostic imaging/*etiology ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; *Microbiota ; Tomography, X-Ray Computed ; Transplantation/*adverse effects ; }, }
@article {pmid25469019, year = {2014}, author = {de Moreno de LeBlanc, A and LeBlanc, JG}, title = {Effect of probiotic administration on the intestinal microbiota, current knowledge and potential applications.}, journal = {World journal of gastroenterology}, volume = {20}, number = {44}, pages = {16518-16528}, pmid = {25469019}, issn = {2219-2840}, mesh = {Animals ; Biological Therapy ; Feces/microbiology ; Humans ; Intestinal Diseases/diagnosis/microbiology/*therapy ; Intestines/*microbiology ; *Microbiota ; Probiotics/*therapeutic use ; Treatment Outcome ; }, abstract = {Although it is now known that the human body is colonized by a wide variety of microbial populations in different parts (such as the mouth, pharynx and respiratory system, the skin, the gastro- and urogenital tracts), many effects of the complex interactions between the human host and microbial symbionts are still not completely understood. The dysbiosis of the gastrointestinal tract microbiota is considered to be one of the most important contributing factors in the development of many gastrointestinal diseases such as inflammatory bowel disease, irritable bowel syndrome and colorectal cancer, as well as systemic diseases like obesity, diabetes, atherosclerosis and non-alcoholic fatty liver disease. Fecal microbial transplantations appear to be promising therapies for dysbiosis-associated diseases; however, probiotic microorganisms have been growing in popularity due to increasing numbers of studies proving that certain strains present health promoting properties, among them the beneficial balance of the intestinal microbiota. Inflammatory bowel diseases and obesity are the pathologies in which there are more studies showing this beneficial association using animal models and even in human clinical trials. In this review, the association of the human gut microbiota and human health will be discussed along with the benefits that probiotics can confer on this symbiotic activity and on the prevention or treatment of associated diseases.}, }
@article {pmid25462985, year = {2015}, author = {Rulli, F and Kartheuser, A and Amirhassankhani, S and Mourad, M and Stefani, M and de Ferrá Aureli, A and Sileri, P and Valentini, PP}, title = {Concept design and simulation study on a "phantom" anvil for circular stapler.}, journal = {Surgical laparoscopy, endoscopy &amp; percutaneous techniques}, volume = {25}, number = {2}, pages = {e72-5}, doi = {10.1097/SLE.0000000000000113}, pmid = {25462985}, issn = {1534-4908}, mesh = {Anastomosis, Surgical/methods ; Colon/*surgery ; Colonic Diseases/*surgery ; Colorectal Surgery/*methods ; *Computer Simulation ; Equipment Design ; Humans ; Surgical Staplers/*standards ; Suture Techniques/*instrumentation ; }, abstract = {INTRODUCTION: Complications and challenges arising from the intraoperative double-stapling technique are seldom reported in colorectal surgery literature. Partial or full-thickness rectal injuries can occur during the introduction and the advancement of the circular stapler along the upper rectum. The aim of this study is to address some of these issues by designing and optimizing a "phantom" anvil manufactured to overcome difficulties throughout the rectal introduction and advancement of the circular stapler for the treatment of benign and malignant colon disease.<br><br>METHODS: The design of the "phantom" anvil has been performed using computer-aided modeling techniques, finite element investigations, and 2 essential keynotes in mind. The first one is the internal shape of the anvil, which is used for the connection to the gun. The second is the shape of the cap, which makes possible the insertion of the gun through the rectum. The "phantom" anvil has 2 functional requirements, which have been taken into account. The design has been optimized to avoid colorectal injuries, neoplastic dissemination (ie, mechanical seeding) and to reduce the fecal contamination.<br><br>RESULTS: Numerical simulations show that a right combination of both top and bottom fillet radii of the shape of the anvil can reduce the stress for the considered anatomic configuration of >90%. Both the fillet radii at the top and the bottom of the device influence the local stress of the colon rectum.<br><br>CONCLUSIONS: A dismountable device, which is used only for the insertion and advancement of the stapler, allows a dedicated design of its shape, keeping the remainder of the stapler unmodified. Computer-aided simulations are useful to perform numerical investigations to optimize the design of this auxiliary part for both the safety of the patient and the ease of the stapler advancement through the rectum.}, }
@article {pmid25462920, year = {2015}, author = {Di Bartolo, I and Angeloni, G and Ponterio, E and Ostanello, F and Ruggeri, FM}, title = {Detection of hepatitis E virus in pork liver sausages.}, journal = {International journal of food microbiology}, volume = {193}, number = {}, pages = {29-33}, doi = {10.1016/j.ijfoodmicro.2014.10.005}, pmid = {25462920}, issn = {1879-3460}, mesh = {Animals ; Feces/virology ; *Food Microbiology ; Genome, Viral ; Genotype ; Hepatitis E virus/genetics/*isolation &amp; purification ; Italy ; Meat Products/*virology ; Norovirus/genetics/*physiology ; Pilot Projects ; Real-Time Polymerase Chain Reaction ; Swine ; }, abstract = {Hepatitis E infection is regarded as an emerging public-health concern. The disease is normally self-limiting (mortality rate 1%), but chronic infections have recently been observed in transplanted patients. The etiological agent HEV is a small RNA virus infecting both humans and animals. In humans, the disease may be food-borne and pig is a main reservoir for zoonotic strains. In the present study, we evaluated the presence of HEV and swine fecal cross-contamination in pork liver sausages sold at a grocery store in Italy. HEV genome detection was performed by RT-qPCR, using harmonized protocols that included a process control (murine norovirus) and an internal amplification control. Swine fecal cross-contamination was assessed by determination of the ubiquitous porcine adenovirus. Overall, HEV genome belonging to genotype 3 was detected in both raw (10 out of 45 slices, 250 mg each, 22.2%) and dry (1 of 23 slices, 4.3%) liver sausages, but infectivity of the virus was not demonstrated. This pilot study fosters more investigations on HEV presence in pork-derived food, to assess the possible risk for the consumers.}, }
@article {pmid25460566, year = {2015}, author = {Khoruts, A and Sadowsky, MJ and Hamilton, MJ}, title = {Development of fecal microbiota transplantation suitable for mainstream medicine.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {13}, number = {2}, pages = {246-250}, doi = {10.1016/j.cgh.2014.11.014}, pmid = {25460566}, issn = {1542-7714}, mesh = {Biomedical Research/trends ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Diseases/*therapy ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; }, abstract = {Fecal microbiota transplantation has emerged as an increasingly common treatment for patients with refractory Clostridium difficile infection. Although it can be relatively simple to perform, a number of challenges need to be overcome before this procedure is widely accepted in mainstream clinical practice. Most of the solutions to these challenges already exist, but some need further optimization and testing. Standardized fecal microbiota is being developed as a therapeutic agent, although it clearly challenges some of the existing paradigms of drug development, delivery, and regulation.}, }
@article {pmid25454597, year = {2015}, author = {García-García-de-Paredes, A and Rodríguez-de-Santiago, E and Aguilera-Castro, L and Ferre-Aracil, C and López-Sanromán, A}, title = {[Fecal microbiota transplantation].}, journal = {Gastroenterologia y hepatologia}, volume = {38}, number = {3}, pages = {123-134}, doi = {10.1016/j.gastrohep.2014.07.010}, pmid = {25454597}, issn = {0210-5705}, mesh = {Animals ; Clinical Trials as Topic ; Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/therapy ; *Fecal Microbiota Transplantation/adverse effects/methods/standards ; Germ-Free Life ; Humans ; Inflammatory Bowel Diseases/microbiology/therapy ; Intestines/immunology/microbiology ; Metabolic Syndrome/microbiology/therapy ; Microbiota ; }, abstract = {Bacteria can no longer be seen as an enemy. Nowadays, there is enough evidence to place the microbiota as a key element in human homeostasis. Despite initial skepticism, fecal microbiota transplantation (FMT) is a real therapeutic alternative for patients with recurrent Clostridium difficile infection. Moreover, this procedure has shown promising results in ulcerative colitis and other non-gastrointestinal disorders. There is still a lack of knowledge and clinical trials with long- term follow-up. Therefore, the available data should be interpreted with caution. In this document we provide a detailed review of the literature on the intestinal microbiota and FMT.}, }
@article {pmid25449389, year = {2015}, author = {Lee, UJ and Ackerman, AL and Wu, A and Zhang, R and Leung, J and Bradesi, S and Mayer, EA and Rodríguez, LV}, title = {Chronic psychological stress in high-anxiety rats induces sustained bladder hyperalgesia.}, journal = {Physiology &amp; behavior}, volume = {139}, number = {}, pages = {541-548}, doi = {10.1016/j.physbeh.2014.11.045}, pmid = {25449389}, issn = {1873-507X}, mesh = {Animals ; Anxiety Disorders/*physiopathology ; Chronic Disease ; Cold Temperature ; Disease Models, Animal ; Electromyography ; Feces ; Female ; Hindlimb/physiopathology ; Hyperalgesia/*physiopathology ; Pain Measurement ; Pain Threshold/physiology ; Physical Stimulation ; Rats, Inbred WKY ; Stress, Psychological/*physiopathology ; Touch ; Urinary Bladder/*physiopathology ; }, abstract = {OBJECTIVE: To evaluate whether anxiety-prone rats exposed to chronic water avoidance stress (WAS) develop visceral bladder hyperalgesia in addition to increased voiding frequency and anxiety-related behaviors.<br><br>MATERIALS AND METHODS: Female Wistar-Kyoto (WKY) rats were exposed to chronic (10-day) WAS or sham paradigms. Referred hyperalgesia and tactile allodynia were tested using von Frey filaments applied to the suprapubic region and plantar region of the hindpaw, respectively. To confirm that suprapubic nociception represented referred visceral bladder hyperalgesia, we recorded abdominal visceromotor responses (VMR) to slow (100 &#x3bc;l/min) and fast (1 cc/sec) bladder filling with room temperature or ice-cold saline. We assessed the development of hyperalgesia over the 10-day WAS protocol and the durability of increased pain sensations over time.<br><br>RESULTS: Animals exposed to chronic WAS had significantly lower hindpaw withdrawal thresholds post-stress and significant differences in referred hyperalgesia. Rats exposed to chronic WAS demonstrated an increased pain response to suprapubic stimulation and decreased response threshold to mechanical hindpaw stimulation by day 8 of the stress protocol, which persisted for more than one month. Animals exposed to chronic WAS showed increased VMR to fast filling and ice water testing in comparison to sham animals. Cystometry under anesthesia did not show increases in the frequency of non-voiding contractions.<br><br>CONCLUSION: Chronic WAS induces sustained bladder hyperalgesia, lasting over a month after exposure to stress. The urinary frequency demonstrated previously in anxiety-prone rats exposed to chronic WAS seems to be associated with bladder hyperalgesia, suggesting that this is a potential model for future studies of bladder hypersensitivity syndromes such as interstitial cystitis/painful bladder syndrome (IC/PBS).}, }
@article {pmid25449172, year = {2014}, author = {Kajon, AE and Lamson, D and Shudt, M and Oikonomopoulou, Z and Fisher, B and Klieger, S and St George, K and Hodinka, RL}, title = {Identification of a novel intertypic recombinant species D human adenovirus in a pediatric stem cell transplant recipient.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {61}, number = {4}, pages = {496-502}, pmid = {25449172}, issn = {1873-5967}, support = {HHSN272201100004C/AI/NIAID NIH HHS/United States ; HHSN272201100040C/AI/NIAID NIH HHS/United States ; HHSN272201000040I/AI/NIAID NIH HHS/United States ; HHSN272201000040C/AI/NIAID NIH HHS/United States ; HHSN2722011000040C//PHS HHS/United States ; }, mesh = {Adenovirus Infections, Human/*virology ; Adenoviruses, Human/*classification/genetics/*isolation &amp; purification ; Child ; DNA, Viral/chemistry/genetics ; Feces/virology ; Female ; Genome, Viral ; Humans ; Molecular Sequence Data ; Plasma/virology ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Stem Cell Transplantation/*adverse effects ; *Transplant Recipients ; Urine/virology ; }, abstract = {BACKGROUND: Human adenoviruses (HAdV) are known opportunistic pathogens in hematopoietic stem cell transplant (SCT) recipients. The detection of HAdV infection in children after SCT has been implicated as a determinant of poor outcome but specific associations between HAdV species or individual HAdV types and disease are poorly understood.<br><br>OBJECTIVES: Characterization of a HAdV-D strain isolated from multiple clinical specimens of an 11-year-old female recipient of a matched unrelated donor peripheral SCT for T-cell lymphoma and case report.<br><br>STUDY DESIGN: Archived HAdV PCR-positive plasma, urine, and stool specimens were processed for virus isolation and detailed molecular typing. Complete genomic sequencing was carried out on 2 isolates.<br><br>RESULTS: The patient tested positive for HAdV DNA by real-time PCR of a stool specimen at 44 days after initiation of a SCT conditioning regimen. In the subsequent 3 months, HAdV was detected in plasma, urine and stool specimens in association with symptoms of gastroenteritis and hemorrhagic cystitis. A novel HAdV-D with a HAdV20-like hexon gene was isolated from both urine and stool specimens. All isolates yielded identical restriction profiles with endonucleases BamHI, BglII, BstEII, HindIII, PstI and SmaI. Analysis of 2 complete genomic sequences further identified the virus as a novel intertypic recombinant HAdV-D (P20/H20/F42) closely related to HAdV42.<br><br>CONCLUSIONS: This case highlights the identification of a previously unknown HAdV-D from an immunocompromised host. In this patient, the course of adenovirus infection is compatible with reactivation of a latent virus or a primary opportunistic infection. Adenoviremia in this patient resolved without definitive adenovirus-directed antiviral therapy.}, }
@article {pmid25448263, year = {2015}, author = {Liu, C and Xiao, L and Li, F and Zhang, H and Li, Q and Liu, H and Fu, S and Li, C and Zhang, X and Wang, J and Staunstrup, NH and Li, Y and Yang, H}, title = {Generation of outbred Ace2 knockout mice by RNA transfection of TALENs displaying colitis reminiscent pathophysiology and inflammation.}, journal = {Transgenic research}, volume = {24}, number = {3}, pages = {433-446}, pmid = {25448263}, issn = {1573-9368}, mesh = {Angiotensin-Converting Enzyme 2 ; Animals ; Base Sequence ; Colitis/chemically induced/genetics/*physiopathology ; Cytokines/genetics/metabolism ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Endonucleases/genetics ; Female ; Germ-Line Mutation ; Male ; *Mice, Knockout ; Microinjections ; Molecular Sequence Data ; Peptidyl-Dipeptidase A/*genetics ; RNA, Messenger ; Transfection/methods ; }, abstract = {The angiotensin I converting enzyme 2 (ACE2) is a key factor in the maintenance of intestinal homeostasis. Dysregulation of homeostasis can lead to inflammation of the colon (colitis), which can cause life-threatening enfeeblement or even cancer. Animal models are valuable surrogates in deciphering the pathology behind such human conditions and for screening of putative therapeutic targets or treatment paradigms. However, development of disease models can be time-consuming and technical demanding, which might hamper their application-value. In this study, we genetically disrupted the mouse Ace2 gene by direct injection of in vitro transcribed mRNA coding for transcription activator-like effector nucleases (TALENs) into the cytoplasm of outbred Kunming mouse zygotes. Consequently, somatic mutations were induced with an efficiency of 57%, of which 39% were frameshift mutations. Moreover, all modifications were stably transferred during germline transmission. In Ace2-knockout male mice (Ace2(-/y)), we observed severe chemical induced colitis, characterized by considerable weight loss, diarrhea and a shortened colon length. Histologically, Ace2 mutations resulted in the infiltration of leukocytes and the overt damage of the intestinal mucosal barrier. In addition, we detected an increased expression of inflammatory cytokines in the colon tissue of Ace2(-/y) mice. Collectively, the data indicate that high targeting efficiency and heritability can be achieved in an outbred mouse model by zygote injection of TALEN mRNA. Furthermore, the generated Ace2(-/y) mice display phenotypic traits reminiscent of colitis and we anticipate that such mice can be of value in studies of the intestinal microbiome or fecal transplantation.}, }
@article {pmid25439277, year = {2014}, author = {Kassam, Z and Lee, CH and Hunt, RH}, title = {Review of the emerging treatment of Clostridium difficile infection with fecal microbiota transplantation and insights into future challenges.}, journal = {Clinics in laboratory medicine}, volume = {34}, number = {4}, pages = {787-798}, doi = {10.1016/j.cll.2014.08.007}, pmid = {25439277}, issn = {1557-9832}, mesh = {Clinical Trials as Topic ; Clostridioides difficile ; Clostridium Infections/*therapy ; Feces/*microbiology ; Humans ; Treatment Outcome ; }, abstract = {Clostridium difficile infection (CDI) is one of the most common health care-associated infections in the United States. Currently, there are no standardized methods to prepare or deliver the fecal microbiota transplantation (FMT). Various methods are used to prepare the FMT, which is usually administered via nasogastric tube, colonoscopy, or by enema. Several clinical trials are underway to assess the true efficacy and safety of FMT for CDI. These trials include CDI studies assessing FMT via colonoscopy and frozen encapsulation, fresh versus frozen-and-thawed FMT by enema, FMT compared with a vancomycin taper, and FMT in the pediatric population.}, }
@article {pmid25436359, year = {2014}, author = {Grąt, M and Hołówko, W and Gałecka, M and Grąt, K and Szachtaz, P and Lewandowsk, Z and Kosińska, I and Schmidts, M and Olejnik-Schmidt, A and Krawczyk, M}, title = {Gut microbiota in cirrhotic liver transplant candidates.}, journal = {Hepato-gastroenterology}, volume = {61}, number = {134}, pages = {1661-1667}, pmid = {25436359}, issn = {0172-6390}, mesh = {Adult ; Bifidobacterium/isolation &amp; purification ; Case-Control Studies ; Enterococcus/isolation &amp; purification ; Feces/microbiology ; Female ; Humans ; Hydrogen Peroxide/metabolism ; Intestines/*microbiology ; Lactobacillus/isolation &amp; purification/metabolism ; Liver Cirrhosis/diagnosis/*microbiology/*surgery ; *Liver Transplantation ; Male ; *Microbiota ; Middle Aged ; Prospective Studies ; Waiting Lists ; }, abstract = {BACKGROUND/AIMS: The purpose of this study was to evaluate the gut microflora of liver transplant candidates.<br><br>METHODOLOGY: Fecal microflora of 20 cirrhotic liver transplant candidates was analyzed basing on prospectively collected stool samples. The results were compared with those of 20 non-cirrhotic patients with liver disease and/or abnormal liver function tests, 20 patients with Crohn&#x2019;s disease, and 20 patients without any gastrointestinal disease. Moreover, correlations between particular counts of microbiota, as well as between microbial counts and stool pH were examined.<br><br>RESULTS: The pattern of fecal microbiota of liver transplant candidates was characterized by increased counts of lactobacilli (p=0.001), including hydrogen peroxide producing strains (p=0.008). In these patients, lactobacilli were positively correlated to enterococci (p=0.006) and bifidobacteria (p=0.004). No correlations other than those observed for lactobacilli in general were observed between hydrogen peroxide producing lactobacilli and the remaining microbiota. Increased yeast and Escherichia coli counts were associated with a tendency towards lower (p=0.095) and higher (p=0.072) stool pH, respectively.<br><br>CONCLUSIONS: Surprisingly, gut microflora of liver transplant candidates with cirrhosis is particularly enriched with lactobacilli, including hydrogen peroxide producing strains. Thus, the use of other potentially beneficial microorganisms, such as particular yeast strains, might be more appropriate for these patients.}, }
@article {pmid25432777, year = {2014}, author = {Zeller, G and Tap, J and Voigt, AY and Sunagawa, S and Kultima, JR and Costea, PI and Amiot, A and Böhm, J and Brunetti, F and Habermann, N and Hercog, R and Koch, M and Luciani, A and Mende, DR and Schneider, MA and Schrotz-King, P and Tournigand, C and Tran Van Nhieu, J and Yamada, T and Zimmermann, J and Benes, V and Kloor, M and Ulrich, CM and von Knebel Doeberitz, M and Sobhani, I and Bork, P}, title = {Potential of fecal microbiota for early-stage detection of colorectal cancer.}, journal = {Molecular systems biology}, volume = {10}, number = {11}, pages = {766}, pmid = {25432777}, issn = {1744-4292}, support = {268985/ERC_/European Research Council/International ; U01 CA206110/CA/NCI NIH HHS/United States ; }, mesh = {Case-Control Studies ; Colorectal Neoplasms/*diagnosis/*microbiology ; Early Detection of Cancer/*methods ; Feces/*microbiology ; Humans ; Metagenomics/methods ; Microbiota ; Molecular Typing ; Occult Blood ; Sensitivity and Specificity ; }, abstract = {Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host-microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.}, }
@article {pmid25430511, year = {2014}, author = {Duke, PS and Fardy, J}, title = {Recurrent Clostridium difficile infection treated with home fecal transplantation: a case report.}, journal = {Journal of medical case reports}, volume = {8}, number = {}, pages = {393}, pmid = {25430511}, issn = {1752-1947}, mesh = {Aged ; *Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Diarrhea/etiology/microbiology/therapy ; Enema/*methods ; *Feces/microbiology ; Female ; Humans ; Recurrence ; Self Care/methods ; Transplants/microbiology ; Treatment Outcome ; }, abstract = {INTRODUCTION: Clostridium difficile infection causes severe diarrhea, abdominal pain and weight loss. A course of metronidazole is the initial treatment; however up to 40% of patients have at least one recurrence. Some patients have recurrent infections requiring further treatment with vancomycin, others need multiple courses of expensive treatment. Fecal transplantation has been proposed as an effective treatment option for patients with recurrences. We report the case of a patient with recurrent Clostridium difficile infection unresponsive to usual treatment and her experience with home fecal transplantation.<br><br>CASE PRESENTATION: A 66-year-old Canadian Caucasian woman presented to her family doctor in December 2012 with a 10-day history of explosive watery diarrhea. She was diagnosed with Clostridium difficile infection and treated with metronidazole. Diarrhea recurred and despite treatment with vancomycin and finally, fidaxomicin, she continued to have recurrent Clostridium difficile infection over the following four months. A formal fecal transplantation program was not available in her home province; therefore home fecal transplantation was performed under supervision by her family physician. This was the first case of fecal transplantation performed in the province and was done outside of a hospital setting. She recovered immediately and has been well for the past year since the procedure.<br><br>CONCLUSIONS: Home fecal transplantation by rectal enema is a viable, safe and practical option for patients with recurrent Clostridium difficile infection. It is less costly and uses fewer resources than traditional delivery methods through nasogastric tube, upper endoscopy or colonoscopy. Patients and their families and donors need medical supervision through the process of screening, telephone availability during the procedure and medical follow-up. This can be done by family physicians without the need for expensive hospital care and subsequent follow-up.}, }
@article {pmid25424663, year = {2015}, author = {Pinn, DM and Aroniadis, OC and Brandt, LJ}, title = {Is fecal microbiota transplantation (FMT) an effective treatment for patients with functional gastrointestinal disorders (FGID)?.}, journal = {Neurogastroenterology and motility}, volume = {27}, number = {1}, pages = {19-29}, doi = {10.1111/nmo.12479}, pmid = {25424663}, issn = {1365-2982}, mesh = {Clostridioides difficile ; Clostridium Infections/microbiology ; Donor Selection ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; Intestines/microbiology ; Irritable Bowel Syndrome/*therapy ; Microbiota ; Treatment Outcome ; }, abstract = {BACKGROUND: Despite its high prevalence and significant effect on quality of life, the etiology of functional gastrointestinal disorders (FGID), and specifically irritable bowel syndrome (IBS), has yet to be fully elucidated. While alterations in immunity, motility, and the brain-gut axis have been implicated in disease pathogenesis, the intestinal microbiota are increasingly being shown to play a role and numerous studies have demonstrated significant differences from normal in the intestinal flora of patients with FGID, and between types of FGID. Fecal microbiota transplantation (FMT) is a curative therapy for Clostridium difficile infection (CDI), a disease hallmarked by intestinal dysbiosis, and FMT is now being explored as a means to also restore intestinal homeostasis in FGID.<br><br>PURPOSE: This review aims to investigate the role of intestinal microbiota in the pathogenesis of FGID, the implications of FMT for the treatment of FGID, and the challenges encountered in measuring response to a specific intervention in patients with FGID.}, }
@article {pmid25420450, year = {2015}, author = {Matsuoka, K and Kanai, T}, title = {The gut microbiota and inflammatory bowel disease.}, journal = {Seminars in immunopathology}, volume = {37}, number = {1}, pages = {47-55}, pmid = {25420450}, issn = {1863-2300}, mesh = {Humans ; Inflammatory Bowel Diseases/immunology/*microbiology ; Intestines/*microbiology ; Microbiota/*immunology ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut. Although the precise cause of IBD remains unknown, the most accepted hypothesis of IBD pathogenesis to date is that an aberrant immune response against the gut microbiota is triggered by environmental factors in a genetically susceptible host. The advancement of next-generation sequencing technology has enabled identification of various alterations of the gut microbiota composition in IBD. While some results related to dysbiosis in IBD are different between studies owing to variations of sample type, method of investigation, patient profiles, and medication, the most consistent observation in IBD is reduced bacterial diversity, a decrease of Firmicutes, and an increase of Proteobacteria. It has not yet been established how dysbiosis contributes to intestinal inflammation. Many of the known IBD susceptibility genes are associated with recognition and processing of bacteria, which is consistent with a role of the gut microbiota in the pathogenesis of IBD. A number of trials have shown that therapies correcting dysbiosis, including fecal microbiota transplantation and probiotics, are promising in IBD.}, }
@article {pmid25417156, year = {2014}, author = {Goodrich, JK and Waters, JL and Poole, AC and Sutter, JL and Koren, O and Blekhman, R and Beaumont, M and Van Treuren, W and Knight, R and Bell, JT and Spector, TD and Clark, AG and Ley, RE}, title = {Human genetics shape the gut microbiome.}, journal = {Cell}, volume = {159}, number = {4}, pages = {789-799}, pmid = {25417156}, issn = {1097-4172}, support = {/WT_/Wellcome Trust/United Kingdom ; DP2 OD007444/OD/NIH HHS/United States ; R01 DK093595/DK/NIDDK NIH HHS/United States ; T32 GM007617/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*classification/*isolation &amp; purification/metabolism ; Body Mass Index ; Feces/*microbiology ; Female ; Gastrointestinal Tract/microbiology ; Germ-Free Life ; Humans ; Male ; Mice ; *Microbiota ; Obesity/microbiology ; Twins, Dizygotic ; Twins, Monozygotic ; }, abstract = {Host genetics and the gut microbiome can both influence metabolic phenotypes. However, whether host genetic variation shapes the gut microbiome and interacts with it to affect host phenotype is unclear. Here, we compared microbiotas across >1,000 fecal samples obtained from the TwinsUK population, including 416 twin pairs. We identified many microbial taxa whose abundances were influenced by host genetics. The most heritable taxon, the family Christensenellaceae, formed a co-occurrence network with other heritable Bacteria and with methanogenic Archaea. Furthermore, Christensenellaceae and its partners were enriched in individuals with low body mass index (BMI). An obese-associated microbiome was amended with Christensenella minuta, a cultured member of the Christensenellaceae, and transplanted to germ-free mice. C. minuta amendment reduced weight gain and altered the microbiome of recipient mice. Our findings indicate that host genetics influence the composition of the human gut microbiome and can do so in ways that impact host metabolism.}, }
@article {pmid25417104, year = {2014}, author = {Thaiss, CA and Zeevi, D and Levy, M and Zilberman-Schapira, G and Suez, J and Tengeler, AC and Abramson, L and Katz, MN and Korem, T and Zmora, N and Kuperman, Y and Biton, I and Gilad, S and Harmelin, A and Shapiro, H and Halpern, Z and Segal, E and Elinav, E}, title = {Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis.}, journal = {Cell}, volume = {159}, number = {3}, pages = {514-529}, doi = {10.1016/j.cell.2014.09.048}, pmid = {25417104}, issn = {1097-4172}, mesh = {Animals ; *Circadian Clocks ; *Circadian Rhythm ; Dysbiosis/microbiology/physiopathology ; Feeding Behavior ; *Glucose Intolerance ; Homeostasis ; Humans ; Jet Lag Syndrome/physiopathology ; Metabolic Diseases/microbiology/physiopathology ; Mice ; *Microbiota ; Obesity/metabolism ; Sleep ; }, abstract = {All domains of life feature diverse molecular clock machineries that synchronize physiological processes to diurnal environmental fluctuations. However, no mechanisms are known to cross-regulate prokaryotic and eukaryotic circadian rhythms in multikingdom ecosystems. Here, we show that the intestinal microbiota, in both mice and humans, exhibits diurnal oscillations that are influenced by feeding rhythms, leading to time-specific compositional and functional profiles over the course of a day. Ablation of host molecular clock components or induction of jet lag leads to aberrant microbiota diurnal fluctuations and dysbiosis, driven by impaired feeding rhythmicity. Consequently, jet-lag-induced dysbiosis in both mice and humans promotes glucose intolerance and obesity that are transferrable to germ-free mice upon fecal transplantation. Together, these findings provide evidence of coordinated metaorganism diurnal rhythmicity and offer a microbiome-dependent mechanism for common metabolic disturbances in humans with aberrant circadian rhythms, such as those documented in shift workers and frequent flyers.}, }
@article {pmid25407220, year = {2015}, author = {Metan, G and Türe, Z and Kaynar, L and Berk, E and Gürsoy, &#x15e; and Alp, E and Kılıç, H and Çetin, M}, title = {Tigecycline for the treatment of Clostridium difficile infection refractory to metronidazole in haematopoietic stem cell transplant recipients.}, journal = {Journal of chemotherapy (Florence, Italy)}, volume = {27}, number = {6}, pages = {354-357}, doi = {10.1179/1973947814Y.0000000225}, pmid = {25407220}, issn = {1973-9478}, mesh = {Adult ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Clostridioides difficile/*drug effects ; Clostridium Infections/*drug therapy ; Drug Resistance, Bacterial ; Fecal Microbiota Transplantation ; Female ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Metronidazole/pharmacology/therapeutic use ; Middle Aged ; Minocycline/*analogs &amp; derivatives/pharmacology/therapeutic use ; Retrospective Studies ; Tigecycline ; Treatment Outcome ; Young Adult ; }, }
@article {pmid25404529, year = {2014}, author = {Lübbert, C and John, E and von Müller, L}, title = {Clostridium difficile infection: guideline-based diagnosis and treatment.}, journal = {Deutsches Arzteblatt international}, volume = {111}, number = {43}, pages = {723-731}, pmid = {25404529}, issn = {1866-0452}, mesh = {Anti-Bacterial Agents/therapeutic use ; Biological Products/therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/*diagnosis/*therapy ; Feces/microbiology ; Humans ; Infectious Disease Medicine/*standards ; *Practice Guidelines as Topic ; }, abstract = {BACKGROUND: Clostridium difficile (C. difficile) is the pathogen that most commonly causes nosocomial and antibiotic-associated diarrheal disease. Optimized algorithms for diagnosis, treatment, and hygiene can help lower the incidence, morbidity, and mortality of C. difficile infection (CDI).<br><br>METHODS: This review is based on pertinent articles that were retrieved by a selective search in PubMed for recommendations on diagnosis and treatment(up to March 2014), with particular attention to the current epidemiological situation in Germany.<br><br>RESULTS: The incidence of CDI in Germany is 5 to 20 cases per 100,000 persons per year. In recent years, a steady increase in severe, reportable cases of CDI has been observed, and the highly virulent epidemic strain Ribotype 027 has spread across nearly the entire country. For therapeutic and hygiene management, it is important that the diagnosis be made as early as possible with a sensitive screening test, followed by a confirmatory test for the toxigenic infection. Special disinfection measures are needed because of the formation of spores. The treatment of CDI is evidence-based; depending on the severity of the infection, it is treated orally with metronidazole, or else with vancomycin or fidaxomicin. Fulminant infections and recurrences call for specifically adapted treatment modalities. Treatment with fecal bacteria (stool transplantation) is performed in gastroenterological centers that have experience with this form of treatment after multiple failures of drug treatment for recurrent infection. For critically ill patients, treatment is administered by an interdisciplinary team and consists of early surgical intervention in combination with drug treatment. A therapeutic algorithm developed on the basis of current guidelines and recommendations enables risk-adapted, individualized treatment.<br><br>CONCLUSION: The growing clinical and epidemiological significance of CDI compels a robust implementation of multimodal diagnostic, therapeutic, and hygienic standards. In the years to come, anti-toxin antibodies, toxoid vaccines, and focused bacterial therapy will be developed as new treatment strategies for CDI.}, }
@article {pmid25401722, year = {2014}, author = {Seril, DN and Shen, B}, title = {Clostridium difficile infection in the postcolectomy patient.}, journal = {Inflammatory bowel diseases}, volume = {20}, number = {12}, pages = {2450-2469}, doi = {10.1097/MIB.0000000000000164}, pmid = {25401722}, issn = {1536-4844}, mesh = {Clostridioides difficile/*pathogenicity ; Clostridium Infections/*etiology ; Colectomy/*adverse effects ; Female ; Humans ; Male ; *Postoperative Complications ; Prognosis ; }, abstract = {Clostridium difficile infection (CDI) after total colectomy has been increasingly recognized over the past decade. C. difficile enteritis (CDE) is a rare occurrence, whereas C. difficile pouchitis (CDP) has been reported in approximately 10% of symptomatic patients seen at a referral center for pouch dysfunction. Similar to colonic CDI in the general population, antibiotic use and comorbid diseases may be risk factors for CDE. In contrast, the postoperative use of antibiotics does not seem to be associated with CDP, whereas male gender, recent hospitalization, and presurgery antibiotic use were shown to be risk factors for CDP. C. difficile is capable of colonizing all intestinal sites, including the ileal pouch. Similarities with the colon at physiological and cellular levels may contribute to the susceptibility of the ileal pouch to CDI. Postcolectomy CDI likely represents a disease spectrum from asymptomatic colonization to severe symptomatic infection. CDI should be considered in ostomy patients with fever and increased ileostomy output and in ileal pouch patients with a change in "normal" symptom pattern or chronic antibiotic-refractory pouchitis. Sensitive and specific methods for detection of CDI are available, and endoscopy is useful in evaluating the patient with suspected CDE or CDP, although pseudomembranes are typically absent. Vancomycin is used as the first-line therapy for CDP and may be warranted for patients with inflammatory bowel disease with CDE. Fecal microbiota transplantation has found its use in the management of severe or antibiotic refractory CDP, but this approach requires evaluation for the management of refractory CDE.}, }
@article {pmid25400998, year = {2014}, author = {Bringiotti, R and Ierardi, E and Lovero, R and Losurdo, G and Di Leo, A and Principi, M}, title = {Intestinal microbiota: The explosive mixture at the origin of inflammatory bowel disease?.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {5}, number = {4}, pages = {550-559}, pmid = {25400998}, issn = {2150-5330}, abstract = {Inflammatory bowel diseases (IBDs), namely Crohn's disease and ulcerative colitis, are lifelong chronic disorders arising from interactions among genetic, immunological and environmental factors. Although the origin of IBDs is closely linked to immune response alterations, which governs most medical decision-making, recent findings suggest that gut microbiota may be involved in IBD pathogenesis. Epidemiologic evidence and several studies have shown that a dysregulation of gut microbiota (i.e., dysbiosis) may trigger the onset of intestinal disorders such as IBDs. Animal and human investigations focusing on the microbiota-IBD relationship have suggested an altered balance of the intestinal microbial population in the active phase of IBD. Rigorous microbiota typing could, therefore, soon become part of a complete phenotypic analysis of IBD patients. Moreover, individual susceptibility and environmental triggers such as nutrition, medications, age or smoking could modify bacterial strains in the bowel habitat. Pharmacological manipulation of bowel microbiota is somewhat controversial. The employment of antibiotics, probiotics, prebiotics and synbiotics has been widely addressed in the literature worldwide, with the aim of obtaining positive results in a number of IBD patient settings, and determining the appropriate timing and modality of this intervention. Recently, novel treatments for IBDs, such as fecal microbiota transplantation, when accepted by patients, have shown promising results. Controlled studies are being designed. In the near future, new therapeutic strategies can be expected, with non-pathogenic or modified food organisms that can be genetically modified to exert anti-inflammatory properties.}, }
@article {pmid25400449, year = {2014}, author = {Chen, WX and Ren, LH and Shi, RH}, title = {Enteric microbiota leads to new therapeutic strategies for ulcerative colitis.}, journal = {World journal of gastroenterology}, volume = {20}, number = {42}, pages = {15657-15663}, pmid = {25400449}, issn = {2219-2840}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Biological Therapy/methods ; Colitis, Ulcerative/diagnosis/microbiology/*therapy ; Diet ; Dysbiosis ; Feces/microbiology ; Homeostasis ; Host-Pathogen Interactions ; Humans ; Intestines/drug effects/*microbiology ; *Microbiota/drug effects ; Prebiotics ; Probiotics/therapeutic use ; Treatment Outcome ; }, abstract = {Ulcerative colitis (UC) is a leading form of inflammatory bowel disease that involves chronic relapsing or progressive inflammation. As a significant proportion of UC patients treated with conventional therapies do not achieve remission, there is a pressing need for the development of more effective therapies. The human gut contains a large, diverse, and dynamic population of microorganisms, collectively referred to as the enteric microbiota. There is a symbiotic relationship between the human host and the enteric microbiota, which provides nutrition, protection against pathogenic organisms, and promotes immune homeostasis. An imbalance of the normal enteric microbiota composition (termed dysbiosis) underlies the pathogenesis of UC. A reduction of enteric microbiota diversity has been observed in UC patients, mainly affecting the butyrate-producing bacteria, such as Faecalibacterium prausnitzii, which can repress pro-inflammatory cytokines. Many studies have shown that enteric microbiota plays an important role in anti-inflammatory and immunoregulatory activities, which can benefit UC patients. Therefore, manipulation of the dysbiosis is an attractive approach for UC therapy. Various therapies targeting a restoration of the enteric microbiota have shown efficacy in treating patients with active and chronic forms of UC. Such therapies include fecal microbiota transplantation, probiotics, prebiotics, antibiotics, helminth therapy, and dietary polyphenols, all of which can alter the abundance and composition of the enteric microbiota. Although there have been many large, randomized controlled clinical trials assessing these treatments, the effectiveness and safety of these bacteria-driven therapies need further evaluation. This review focuses on the important role that the enteric microbiota plays in maintaining intestinal homeostasis and discusses new therapeutic strategies targeting the enteric microbiota for UC.}, }
@article {pmid25394235, year = {2015}, author = {El Feghaly, RE and Bangar, H and Haslam, DB}, title = {The molecular basis of Clostridium difficile disease and host response.}, journal = {Current opinion in gastroenterology}, volume = {31}, number = {1}, pages = {24-29}, doi = {10.1097/MOG.0000000000000131}, pmid = {25394235}, issn = {1531-7056}, support = {P30 DK078392/DK/NIDDK NIH HHS/United States ; UL1TR000077/TR/NCATS NIH HHS/United States ; }, mesh = {Biomarkers/metabolism ; Clostridioides difficile/*pathogenicity/physiology ; Enterocolitis, Pseudomembranous/diagnosis/*genetics/*microbiology/therapy ; Feces/microbiology ; Host-Pathogen Interactions ; Humans ; Microbiota ; Tissue Transplantation/methods ; }, abstract = {PURPOSE OF REVIEW: Clostridium difficile infection (CDI) ranges from asymptomatic colonization to severe colitis and death. The physiologic and molecular mechanisms determining disease outcome are thus far poorly understood. Here, we review recent advances in the relationship between host response to infection and disease outcome. Furthermore, we review recent studies on the relationship between intestinal microbial ecology and pathogenesis of CDI.<br><br>RECENT FINDINGS: Severe CDI is characterized by toxin-induced epithelial injury and marked intestinal inflammation. Recent studies demonstrate that systemic markers of inflammation correlate with disease outcome. Peripheral neutrophil count, C-reactive protein, and proinflammatory cytokines are elevated in patients with severe disease as compared with asymptomatic controls. Furthermore, fecal inflammatory biomarkers are better predictors of disease severity and diarrhea persistence than C. difficile abundance. A landmark study reported higher than 80% success rate of fecal microbiota transplantation for treatment of recurrent CDI. The commensal microbes responsible for C. difficile protection, and the molecular basis by which microbial ecology impacts disease outcome, are under active investigation.<br><br>SUMMARY: Under conditions of altered microbial ecology, C. difficile incites epithelial injury and marked intestinal inflammation, the primary determinant of disease outcome. Restoration of a diverse intestinal microbial population by fecal microbiota transplantation attenuates disease and prevents recurrence by mechanisms that are yet to be fully elucidated.}, }
@article {pmid25389085, year = {2014}, author = {Liang, J and Sha, SM and Wu, KC}, title = {Role of the intestinal microbiota and fecal transplantation in inflammatory bowel diseases.}, journal = {Journal of digestive diseases}, volume = {15}, number = {12}, pages = {641-646}, doi = {10.1111/1751-2980.12211}, pmid = {25389085}, issn = {1751-2980}, mesh = {Biological Therapy/*methods ; Escherichia coli ; Feces/*microbiology ; Genetic Predisposition to Disease ; Humans ; *Inflammatory Bowel Diseases/genetics/microbiology/pathology/therapy ; Intestines/*microbiology ; *Microbiota ; Mycobacterium avium subsp. paratuberculosis ; }, abstract = {Ulcerative colitis and Crohn's disease are the two major types of inflammatory bowel disease (IBD). Despite intensive study, it is still challenging because the precise etiology and pathogenesis remains unclear. Studies have shown that IBD is associated with changes in the composition of intestinal microbiota, as either a cause or a consequence of abnormal host immune response in genetic susceptible population. Two specific microorganisms (Mycobacterium avium subsp. paratuberculosis and Escherichia coli) get more widely studied, but till now no single microorganism has been identified as the only pathogen. Genetic susceptibility data also suggest impaired handling of bacteria as well as an improper immune response to potential pathogens. The microbiota provides new therapeutic methods, and fecal microbiota transplantation may restore the balance of intestinal flora to supplement or optimize the current therapies.}, }
@article {pmid25373861, year = {2015}, author = {Russell, GH}, title = {Too early to determine whether fecal microbiota transplant has therapeutic promise for Ulcerative Colitis?.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {60}, number = {1}, pages = {3}, doi = {10.1097/MPG.0000000000000619}, pmid = {25373861}, issn = {1536-4801}, mesh = {Attitude of Health Personnel ; Attitude to Health ; Child ; Colitis, Ulcerative/microbiology/*therapy ; Feces/microbiology ; Humans ; *Microbiota ; *Therapies, Investigational ; }, }
@article {pmid25373588, year = {2014}, author = {Li, Q and Wang, C and Tang, C and He, Q and Zhao, X and Li, N and Li, J}, title = {Therapeutic modulation and reestablishment of the intestinal microbiota with fecal microbiota transplantation resolves sepsis and diarrhea in a patient.}, journal = {The American journal of gastroenterology}, volume = {109}, number = {11}, pages = {1832-1834}, doi = {10.1038/ajg.2014.299}, pmid = {25373588}, issn = {1572-0241}, mesh = {Adult ; Biological Therapy/*methods ; Diarrhea/*therapy ; Feces/*microbiology ; Female ; Homeostasis ; Humans ; *Microbiota ; Sepsis/*therapy ; Treatment Outcome ; }, }
@article {pmid25373585, year = {2014}, author = {Pinn, DM and Aroniadis, OC and Brandt, LJ}, title = {Is fecal microbiota transplantation the answer for irritable bowel syndrome? A single-center experience.}, journal = {The American journal of gastroenterology}, volume = {109}, number = {11}, pages = {1831-1832}, doi = {10.1038/ajg.2014.295}, pmid = {25373585}, issn = {1572-0241}, mesh = {Biological Therapy/*methods ; Feces/*microbiology ; Female ; Homeostasis ; Humans ; Irritable Bowel Syndrome/*therapy ; Male ; *Microbiota ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; }, }
@article {pmid25369668, year = {2014}, author = {Storr, M and Starostzik, C}, title = {[Stool transplantation: also an option for irritable bowel syndrome?].}, journal = {MMW Fortschritte der Medizin}, volume = {156}, number = {12}, pages = {16}, pmid = {25369668}, issn = {1438-3276}, mesh = {Allografts ; Colonoscopy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Germany ; Humans ; Irritable Bowel Syndrome/*therapy ; Isografts ; *Microbiota ; Recurrence ; Treatment Outcome ; }, }
@article {pmid25369667, year = {2014}, author = {Starostzik Christine, }, title = {["Will you give me your stool?"].}, journal = {MMW Fortschritte der Medizin}, volume = {156}, number = {12}, pages = {14-15}, pmid = {25369667}, issn = {1438-3276}, mesh = {Allografts ; Colonoscopy ; Enterocolitis, Pseudomembranous/*microbiology/*therapy ; Feces/*microbiology ; Humans ; Intestines/*microbiology ; Intubation, Gastrointestinal ; Isografts ; *Microbiota ; Treatment Outcome ; }, }
@article {pmid25366338, year = {2014}, author = {Varier, RU and Biltaji, E and Smith, KJ and Roberts, MS and Jensen, MK and LaFleur, J and Nelson, RE}, title = {Cost-effectiveness analysis of treatment strategies for initial Clostridium difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {20}, number = {12}, pages = {1343-1351}, doi = {10.1111/1469-0691.12805}, pmid = {25366338}, issn = {1469-0691}, support = {UL1TR001067/TR/NCATS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*economics/*therapeutic use ; Biological Therapy/*economics/*methods ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*economics/microbiology/*therapy ; Computer Simulation ; Cost-Benefit Analysis ; Humans ; Metronidazole/economics/therapeutic use ; Quality-Adjusted Life Years ; Vancomycin/economics/therapeutic use ; }, abstract = {Clostridium difficile infection (CDI) is costly. Current guidelines recommend metronidazole as first-line therapy and vancomycin as an alternative. Recurrence is common. Faecal microbiota transplantation (FMT) is an effective therapy for recurrent CDI (RCDI). This study explores the cost-effectiveness of FMT, vancomycin and metronidazole for initial CDI. We constructed a decision-analytic computer simulation using inputs from published literature to compare FMT with a 10-14-day course of oral metronidazole or vancomycin for initial CDI. Parameters included cure rates (baseline value (range)) for metronidazole (80% (65-85%)), vancomycin (90% (88-92%)) and FMT(91% (83-100%)). Direct costs of metronidazole, vancomycin and FMT, adjusted to 2011 dollars, were $57 ($43-72), $1347 ($1195-1499) and $1086 ($815-1358), respectively. Our effectiveness measure was quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were conducted from the third-party payer perspective. Analysis using baseline values showed that FMT($1669, 0.242 QALYs) dominated (i.e. was less costly and more effective) vancomycin ($1890, 0.241 QALYs). FMT was more costly and more effective than metronidazole ($1167, 0.238 QALYs), yielding an incremental cost-effectiveness ratio (ICER) of $124 964/QALY. One-way sensitivity analyses showed that metronidazole dominated both strategies if its probability of cure were >90%; FMT dominated if it cost <$584. In a probabilistic sensitivity analysis at a willingness-to-pay threshold of $100 000/QALY, metronidazole was favoured in 55% of model iterations; FMT was favoured in 38%. Metronidazole, as the first-line treatment for CDIs, is less costly. FMT and vancomycin are more effective. However, FMT is less likely to be economically favourable, and vancomycin is unlikely to be favourable as first-line therapy when compared with FMT.}, }
@article {pmid25356041, year = {2014}, author = {Wang, ZK and Yang, YS and Chen, Y and Yuan, J and Sun, G and Peng, LH}, title = {Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease.}, journal = {World journal of gastroenterology}, volume = {20}, number = {40}, pages = {14805-14820}, pmid = {25356041}, issn = {2219-2840}, mesh = {Animals ; Biological Therapy/*methods ; Feces/*microbiology ; Host-Pathogen Interactions ; Humans ; Immunity, Mucosal ; Inflammatory Bowel Diseases/diagnosis/immunology/microbiology/*therapy ; Intestines/immunology/*microbiology ; *Microbiota ; Probiotics/therapeutic use ; Treatment Outcome ; }, abstract = {The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models.}, }
@article {pmid25355279, year = {2015}, author = {Satokari, R and Mattila, E and Kainulainen, V and Arkkila, PE}, title = {Simple faecal preparation and efficacy of frozen inoculum in faecal microbiota transplantation for recurrent Clostridium difficile infection--an observational cohort study.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {41}, number = {1}, pages = {46-53}, doi = {10.1111/apt.13009}, pmid = {25355279}, issn = {1365-2036}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; Colon/*microbiology ; Colonoscopy ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; Middle Aged ; Retrospective Studies ; Tissue Donors ; Tissue Transplantation/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The finding of suitable donor, donor screening and preparation of faecal transplants are challenging in clinical work.<br><br>AIM: To develop a practical protocol for preparing frozen transplants and to compare the efficacy of previously frozen and fresh faeces in treating rCDI.<br><br>METHODS: Two healthy volunteers acted as universal donors for the frozen faecal preparations, which were prepared by suspending faeces into physiological saline, adding glycerol to a final concentration of 10% and storing at -80&#xa0;&#xb0;C. We compared the outcomes of patients with rCDI who had undergone FMT at colonoscopy and received infusion of previously prepared, freeze-stored faeces (n&#xa0;=&#xa0;23) or fresh faeces from individual (n&#xa0;=&#xa0;15) or universal donors (n&#xa0;=&#xa0;11) (total n&#xa0;=&#xa0;49). Clinical failure was defined as persistent or recurrent symptoms with a positive C.&#xa0;difficile toxin stool test, and a need for new therapy.<br><br>RESULTS: At 12&#xa0;weeks post-FMT, symptoms were resolved in 22 of 23 patients receiving previously frozen faeces, and in all 11 or 14 of 15 patients receiving fresh faeces from the universal or individual donors respectively (totally 25 of 26; P&#xa0;=&#xa0;ns, success rate 96%). Mild transient fever appeared for two patients receiving frozen faeces, but no other significant side effects were observed. 42 patients were followed up for a year post-FMT and the success rate was 88% in both fresh and frozen faeces groups.<br><br>CONCLUSIONS: Preparation of frozen transplants simplifies the practical aspects of faecal microbiota transplantation without loss of efficacy or safety.}, }
@article {pmid25354973, year = {2015}, author = {Yücesoy, AN and Cifçi, M and Poçan, S}, title = {Anal sphincteroplasty and gracilis muscle transposition using transvaginal access in a patient with fecal incontinence.}, journal = {Techniques in coloproctology}, volume = {19}, number = {1}, pages = {53-56}, doi = {10.1007/s10151-014-1221-1}, pmid = {25354973}, issn = {1128-045X}, mesh = {Adult ; Anal Canal/injuries/*surgery ; Fecal Incontinence/*surgery ; Female ; Humans ; Medical Illustration ; Muscle, Skeletal/*surgery ; Photography ; Thigh ; Transplant Donor Site ; Vagina/*surgery ; }, }
@article {pmid25350805, year = {2014}, author = {Drekonja, DM}, title = {Clostridium difficile infection: current, forgotten and emerging treatment options.}, journal = {Journal of comparative effectiveness research}, volume = {3}, number = {5}, pages = {547-557}, doi = {10.2217/cer.14.36}, pmid = {25350805}, issn = {2042-6313}, mesh = {Anti-Bacterial Agents/economics/therapeutic use ; *Clostridioides difficile ; Clostridium Infections/drug therapy/economics/*therapy ; Cost-Benefit Analysis/economics/methods ; Cross Infection/drug therapy/therapy ; Feces/microbiology ; Humans ; Microbiota ; Vaccination/methods ; }, abstract = {Clostridium difficile infection (CDI) has increased in incidence and severity, and is now among the most common nosocomial infections. Several agents are available for the initial treatment of CDI, some of which are rarely used, and none of which is clearly superior for initial clinical cure. Fidaxomicin appears to offer a benefit in terms of preventing recurrent disease, although the cost-benefit ratio is debated. Recurrent CDI is a major challenge, occurring after 15-30% of initial episodes. The treatment of recurrent CDI is difficult, with sparse evidence available to support any particular agent. Fecal microbiota therapy, also known as 'stool transplantation', appears to be highly effective, although availability is currently limited, and the regulatory environment is in flux. Synthetic stool products and an orally available fecal microbiota therapy product are both under investigation, which may address the problem of availability. As with most infectious diseases, an effective vaccine would be a welcome addition to our armamentarium, but none is currently available.}, }
@article {pmid25345825, year = {2015}, author = {Peterson, CT and Sharma, V and Elmén, L and Peterson, SN}, title = {Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota.}, journal = {Clinical and experimental immunology}, volume = {179}, number = {3}, pages = {363-377}, pmid = {25345825}, issn = {1365-2249}, mesh = {Animals ; *Bacteria ; *Biological Therapy ; Dysbiosis/*immunology/microbiology ; Homeostasis ; Humans ; Immune System ; Immunity, Mucosal ; Immunomodulation ; Intestines/*immunology/microbiology ; Microbiota/immunology ; Probiotics/*therapeutic use ; }, abstract = {The distal gut harbours ∼10(13) bacteria, representing the most densely populated ecosystem known. The functional diversity expressed by these communities is enormous and relatively unexplored. The past decade of research has unveiled the profound influence that the resident microbial populations bestow to host immunity and metabolism. The evolution of these communities from birth generates a highly adapted and highly personalized microbiota that is stable in healthy individuals. Immune homeostasis is achieved and maintained due in part to the extensive interplay between the gut microbiota and host mucosal immune system. Imbalances of gut microbiota may lead to a number of pathologies such as obesity, type I and type II diabetes, inflammatory bowel disease (IBD), colorectal cancer (CRC) and inflammaging/immunosenscence in the elderly. In-depth understanding of the underlying mechanisms that control homeostasis and dysbiosis of the gut microbiota represents an important step in our ability to reliably modulate the gut microbiota with positive clinical outcomes. The potential of microbiome-based therapeutics to treat epidemic human disease is of great interest. New therapeutic paradigms, including second-generation personalized probiotics, prebiotics, narrow spectrum antibiotic treatment and faecal microbiome transplantation, may provide safer and natural alternatives to traditional clinical interventions for chronic diseases. This review discusses host-microbiota homeostasis, consequences of its perturbation and the associated challenges in therapeutic developments that lie ahead.}, }
@article {pmid25344853, year = {2014}, author = {Vigvári, S and Nemes, Z and Vincze, A and Solt, J and Sipos, D and Feiszt, Z and Kappéter, A and Kovács, B and Péterfi, Z}, title = {[Experience with fecal transplantation in the treatment of Clostridium difficile infection].}, journal = {Orvosi hetilap}, volume = {155}, number = {44}, pages = {1758-1762}, doi = {10.1556/OH.2014.30020}, pmid = {25344853}, issn = {0030-6002}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biological Therapy/*methods ; *Clostridioides difficile ; Clostridium Infections/therapy ; Enterocolitis, Pseudomembranous/*therapy ; *Feces/microbiology ; Female ; Humans ; Male ; *Microbiota ; Middle Aged ; Transplantation/methods ; Treatment Outcome ; }, abstract = {INTRODUCTION: During the past years a dramatic change has been observed in the epidemiology of Clostridium difficile infections.<br><br>AIM: The aim of the authors was to investigate the possibility of the fecal microbiota transplantation and study differences, if any, in the success rate of the two different upper gastrointestinal tract method.<br><br>METHOD: 100 ml of fecal microbiota solution was instilled via a nasoduodenal tube in 15 cases and a nasogastric tube in 15 cases. The authors defined the primary cure rate as the percentage of cases in which the symptoms disappeared without recurrence within 6 weeks after the first fecal microbiota transplantation, while secondary cure rate was calculated as the percentage of cases in which the symptoms resolved after the second fecal microbiota transplantation.<br><br>RESULTS: It was found that fecal microbiota transplantation applied via the nasoduodenal tube resulted in a 100% primary cure rate. With the use of the nasogastric tube, the primary and secondary cure rate were 80% and 93.3%, respectively. Fecal microbiota transplantation via the upper gastrointestinal tract was found to have an overall primary cure rate of 90.0% and a secondary cure rate of 96.7%.<br><br>CONCLUSIONS: Fecal microbiota transplantation proved to be very effective, particularly in recurrent infections and cases where conventional treatment failed.}, }
@article {pmid25340496, year = {2014}, author = {Ianiro, G and Bibbò, S and Scaldaferri, F and Gasbarrini, A and Cammarota, G}, title = {Fecal microbiota transplantation in inflammatory bowel disease: beyond the excitement.}, journal = {Medicine}, volume = {93}, number = {19}, pages = {e97}, pmid = {25340496}, issn = {1536-5964}, mesh = {Biological Therapy/*methods ; Clinical Trials as Topic ; Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Microbiota/*physiology ; Outcome Assessment, Health Care ; Transplants/*physiology ; }, abstract = {The purpose of this article is to perform a systematic review of the literature on the use of fecal microbiota transplantation (FMT) in inflammatory bowel disease (IBD).There is an increasing interest of both physicians and patients in assessing the possible role of the FMT in the treatment of IBD.Electronic and manual bibliographic searches were performed to identify original reports in which subjects with IBD were treated with FMT. Because of the scarcity of studies with adequate sample size, case series and case reports were also considered. A critical appraisal of the clinical research evidence on the effectiveness, safety, and other parameters related to FMT was made. Data extraction was independently performed by 2 reviewers.We found a total of 31 publications on the use of FMT in IBD. The majority were case reports or case series, whereas 8 publications reported data from open-label trials including a very less number of patients. A total of 133 patients with IBD were managed with FMT. Of these, 57 subjects (43%) had a Clostridium difficile infection. A resolution or reduction of symptoms was reported in 80 of 113 (71%) patients with evaluable IBD. Moreover, FMT does not seem to provide the same safety profile showed for non-IBD individuals with C difficile infection.The available evidence is limited and weak. FMT has the potential to be somehow of help in managing patients with IBD, but considerable further efforts are necessary to make this procedure a valid option for these subjects.}, }
@article {pmid25339800, year = {2014}, author = {Kennedy, PJ and Cryan, JF and Dinan, TG and Clarke, G}, title = {Irritable bowel syndrome: a microbiome-gut-brain axis disorder?.}, journal = {World journal of gastroenterology}, volume = {20}, number = {39}, pages = {14105-14125}, pmid = {25339800}, issn = {2219-2840}, mesh = {Animals ; Brain/*physiopathology ; Cognition ; Host-Pathogen Interactions ; Humans ; Intestines/*innervation/*microbiology ; Irritable Bowel Syndrome/*microbiology/physiopathology/psychology/therapy ; *Microbiota ; Pain Perception ; Prognosis ; Risk Factors ; Stress, Psychological/microbiology/physiopathology/psychology ; }, abstract = {Irritable bowel syndrome (IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions.}, }
@article {pmid25337874, year = {2015}, author = {Buffie, CG and Bucci, V and Stein, RR and McKenney, PT and Ling, L and Gobourne, A and No, D and Liu, H and Kinnebrew, M and Viale, A and Littmann, E and van den Brink, MR and Jenq, RR and Taur, Y and Sander, C and Cross, JR and Toussaint, NC and Xavier, JB and Pamer, EG}, title = {Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile.}, journal = {Nature}, volume = {517}, number = {7533}, pages = {205-208}, pmid = {25337874}, issn = {1476-4687}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; T32GM07739/GM/NIGMS NIH HHS/United States ; R01 AI42135/AI/NIAID NIH HHS/United States ; DP2 OD008440/OD/NIH HHS/United States ; R37 AI039031/AI/NIAID NIH HHS/United States ; U54 CA148967/CA/NCI NIH HHS/United States ; DP2OD008440/OD/NIH HHS/United States ; K23 AI095398/AI/NIAID NIH HHS/United States ; T32 CA009149/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; AI95706/AI/NIAID NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; T32 GM007739/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bile Acids and Salts/*metabolism ; Biological Evolution ; Clostridioides difficile/drug effects/*physiology ; Clostridium/metabolism ; Colitis/metabolism/microbiology/prevention &amp; control/therapy ; Disease Susceptibility/*microbiology ; Feces/microbiology ; Female ; Humans ; Intestinal Mucosa/*metabolism ; Intestines/drug effects/*microbiology ; Metagenome/genetics ; Mice ; Mice, Inbred C57BL ; Microbiota/drug effects/genetics/*physiology ; Symbiosis ; }, abstract = {The gastrointestinal tracts of mammals are colonized by hundreds of microbial species that contribute to health, including colonization resistance against intestinal pathogens. Many antibiotics destroy intestinal microbial communities and increase susceptibility to intestinal pathogens. Among these, Clostridium difficile, a major cause of antibiotic-induced diarrhoea, greatly increases morbidity and mortality in hospitalized patients. Which intestinal bacteria provide resistance to C. difficile infection and their in vivo inhibitory mechanisms remain unclear. Here we correlate loss of specific bacterial taxa with development of infection, by treating mice with different antibiotics that result in distinct microbiota changes and lead to varied susceptibility to C. difficile. Mathematical modelling augmented by analyses of the microbiota of hospitalized patients identifies resistance-associated bacteria common to mice and humans. Using these platforms, we determine that Clostridium scindens, a bile acid 7α-dehydroxylating intestinal bacterium, is associated with resistance to C. difficile infection and, upon administration, enhances resistance to infection in a secondary bile acid dependent fashion. Using a workflow involving mouse models, clinical studies, metagenomic analyses, and mathematical modelling, we identify a probiotic candidate that corrects a clinically relevant microbiome deficiency. These findings have implications for the rational design of targeted antimicrobials as well as microbiome-based diagnostics and therapeutics for individuals at risk of C. difficile infection.}, }
@article {pmid25333427, year = {2014}, author = {Srigley, JA and Furness, CD and Gardam, M}, title = {Measurement of patient hand hygiene in multiorgan transplant units using a novel technology: an observational study.}, journal = {Infection control and hospital epidemiology}, volume = {35}, number = {11}, pages = {1336-1341}, doi = {10.1086/678419}, pmid = {25333427}, issn = {1559-6834}, mesh = {*Computer Systems ; Cross-Sectional Studies ; Epidemiological Monitoring ; Female ; Hand Hygiene/*statistics &amp; numerical data ; Hand Sanitizers ; *Health Behavior ; Humans ; Inpatients/*statistics &amp; numerical data ; Male ; Meals ; Middle Aged ; Organ Transplantation ; Sex Factors ; Soaps ; Toilet Facilities ; }, abstract = {OBJECTIVE: Healthcare worker hand hygiene is known to prevent healthcare-associated infections, but there are few data on patient hand hygiene despite the fact that nosocomial pathogens may be acquired by patients via their own unclean hands. The purpose of this study was to measure patient hand hygiene behavior in the hospital after visiting a bathroom, before eating, and on entering and leaving their rooms.<br><br>DESIGN: Cross-sectional study.<br><br>SETTING: Acute care teaching hospital in Canada.<br><br>PATIENTS: Convenience sample of 279 adult patients admitted to 3 multiorgan transplant units between July 2012 and March 2013.<br><br>METHODS: Patient use of alcohol-based hand rub and soap dispensers was measured using an ultrasound-based real-time location system during visits to bathrooms, mealtimes, kitchen visits, and on entering and leaving their rooms.<br><br>RESULTS: Overall, patients performed hand hygiene during 29.7% of bathroom visits, 39.1% of mealtimes, 3.3% of kitchen visits, 2.9% of room entries, and 6.7% of room exits.<br><br>CONCLUSIONS: Patients appear to perform hand hygiene infrequently, which may contribute to transmission of pathogens from the hospital environment via indirect contact or fecal-oral routes.}, }
@article {pmid25327204, year = {2014}, author = {Espinoza, R and Quera, R and Meyer, L and Rivera, D}, title = {[Fecal microbiota transplantation: first case report in Chile and review].}, journal = {Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia}, volume = {31}, number = {4}, pages = {477-482}, doi = {10.4067/S0716-10182014000400016}, pmid = {25327204}, issn = {0716-1018}, mesh = {Bacteremia/microbiology ; Biological Therapy/*adverse effects/methods ; Chile ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Crohn Disease/microbiology ; Escherichia coli Infections/*etiology ; Feces/*microbiology ; Humans ; Male ; *Microbiota ; Middle Aged ; Recurrence ; Transplantation ; }, abstract = {Clostridium difficile (CD) infection is increasing in frequency and severity in in-hospital and outpatient clinical settings, with a recurrence that can reach 30% after first episode. The recurrences are usually treated with longer courses of metronidazole or vancomycin. Other treatments have been used, such as probiotics, fidaxomicin, rifaximin, immunoglobulins and monoclonal antibodies against toxins A and B. Fecal microbiota transplantation (FMT) has emerged as a promising strategy in this group of patients, with effectiveness greater than 90%. We present the first case reported in Chile of this therapeutic strategy in a patient with Crohn's disease and recurrent CD infection who presented after the fecal transplantation an Escherichia coli bacteremia, suggesting the need for caution in the use of this strategy. 10 months after the FMT the patient presented a new episode of E. coli bacteremia and two episodes of diarrhea due to CD infection, treated both of them with vancomycin with good clinical response.}, }
@article {pmid25322359, year = {2014}, author = {Youngster, I and Russell, GH and Pindar, C and Ziv-Baran, T and Sauk, J and Hohmann, EL}, title = {Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection.}, journal = {JAMA}, volume = {312}, number = {17}, pages = {1772-1778}, doi = {10.1001/jama.2014.13875}, pmid = {25322359}, issn = {1538-3598}, support = {8UL1TR000170-05/TR/NCATS NIH HHS/United States ; }, mesh = {Administration, Oral ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Capsules ; Child ; *Clostridioides difficile ; Cryopreservation ; Diarrhea/etiology/therapy ; Enterocolitis, Pseudomembranous/complications/*therapy ; Feces/*microbiology ; Female ; Healthy Volunteers ; Humans ; Male ; *Microbiota ; Middle Aged ; Secondary Prevention ; Transplantation/adverse effects/*methods ; Treatment Outcome ; Young Adult ; }, abstract = {IMPORTANCE: Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use.<br><br>OBJECTIVE: To evaluate the safety and rate of resolution of diarrhea following administration of frozen FMT capsules from prescreened unrelated donors to patients with recurrent C. difficile infection.<br><br>Open-label, single-group, preliminary feasibility study conducted from August 2013 through June 2014 at Massachusetts General Hospital, Boston. Twenty patients (median age, 64.5 years; range, 11-89 years) with at least 3 episodes of mild to moderate C. difficile infection and failure of a 6- to 8-week taper with vancomycin or at least 2 episodes of severe C. difficile infection requiring hospitalization were enrolled.<br><br>INTERVENTIONS: Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at -80&#xb0;C (-112&#xb0;F). Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months.<br><br>MAIN OUTCOMES AND MEASURES: The primary end points were safety, assessed by adverse events of grade 2 or above, and clinical resolution of diarrhea with no relapse at 8 weeks. Secondary end points included improvement in subjective well-being per standardized questionnaires and daily number of bowel movements.<br><br>RESULTS: No serious adverse events attributed to FMT were observed. Resolution of diarrhea was achieved in 14 patients (70%; 95% CI, 47%-85%) after a single capsule-based FMT. All 6 nonresponders were re-treated; 4 had resolution of diarrhea, resulting in an overall 90% (95% CI, 68%-98%) rate of clinical resolution of diarrhea (18/20). Daily number of bowel movements decreased from a median of 5 (interquartile range [IQR], 3-6) the day prior to administration to 2 (IQR, 1-3) at day 3 (P&#x2009;=&#x2009;.001) and 1 (IQR, 1-2) at 8 weeks (P&#x2009;<&#x2009;.001). Self-ranked health scores improved significantly on a scale of 1 to 10 from a median of 5 (IQR, 5-7) for overall health and 4.5 (IQR, 3-7) for gastrointestinal-specific health on the day prior to FMT to 8 (IQR, 7-9) after FMT administration for both overall and gastrointestinal health (P&#x2009;=&#x2009;.001). Patients needing a second treatment to obtain resolution of diarrhea had lower pretreatment health scores (median, 6.5 [IQR, 5-7.3] vs 5 [IQR, 2.8-5]; P&#x2009;=&#x2009;.02).<br><br>CONCLUSIONS AND RELEVANCE: This preliminary study among patients with relapsing C. difficile infection provides data on adverse events and rates of resolution of diarrhea following administration of FMT using frozen encapsulated inoculum from unrelated donors. Larger studies are needed to confirm these results and to evaluate long-term safety and effectiveness.<br><br>TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01914731.}, }
@article {pmid25321166, year = {2014}, author = {Ren, Z and Jiang, J and Lu, H and Chen, X and He, Y and Zhang, H and Xie, H and Wang, W and Zheng, S and Zhou, L}, title = {Intestinal microbial variation may predict early acute rejection after liver transplantation in rats.}, journal = {Transplantation}, volume = {98}, number = {8}, pages = {844-852}, pmid = {25321166}, issn = {1534-6080}, mesh = {Acute Disease ; Animals ; Denaturing Gradient Gel Electrophoresis ; Graft Rejection/*etiology/microbiology ; Intestines/*microbiology ; Liver Transplantation/*adverse effects ; Phylogeny ; Rats, Inbred Lew ; Toll-Like Receptors/physiology ; }, abstract = {BACKGROUND: Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT.<br><br>METHODS: The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis.<br><br>RESULTS: Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-&#x3b1;.<br><br>CONCLUSION: We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT.}, }
@article {pmid25320572, year = {2014}, author = {Barker, A and Hurley, J}, title = {Novel treatment options for fecal incontinence.}, journal = {Clinics in colon and rectal surgery}, volume = {27}, number = {3}, pages = {116-120}, pmid = {25320572}, issn = {1531-0043}, abstract = {Fecal incontinence (FI) is a devastating condition affecting a substantial portion of the population. The etiologies of FI are wide ranging, as are the treatment options. When conservative measures fail, often surgical intervention is required. As in any area where a wide range of treatment options exist, there is no one perfect solution. Fortunately, novel treatment options for FI are becoming available, namely, posterior tibial nerve stimulation, magnetic anal sphincter, stem cell transplant, pyloric transplantation, and acupuncture.}, }
@article {pmid25319933, year = {2015}, author = {Kuscher, S and Kronberger, I and Oberwalder, M and Biebl, M and Pratschke, J and Bruder, E and Aigner, F}, title = {Rare morphological disorder in therapy refractory chronic constipation.}, journal = {International journal of colorectal disease}, volume = {30}, number = {4}, pages = {579-580}, pmid = {25319933}, issn = {1432-1262}, mesh = {Adult ; Atrophy ; Chronic Disease ; Colectomy ; Colon/*pathology ; Constipation/*pathology/physiopathology/surgery ; Fecal Incontinence/etiology/surgery ; Female ; Gastrointestinal Transit ; Humans ; Postoperative Complications ; Rectal Prolapse/etiology/surgery ; }, }
@article {pmid25315967, year = {2015}, author = {Chen, J and Waddell, A and Lin, YD and Cantorna, MT}, title = {Dysbiosis caused by vitamin D receptor deficiency confers colonization resistance to Citrobacter rodentium through modulation of innate lymphoid cells.}, journal = {Mucosal immunology}, volume = {8}, number = {3}, pages = {618-626}, pmid = {25315967}, issn = {1935-3456}, support = {R01 AT005378/AT/NCCIH NIH HHS/United States ; R01 NS067563/NS/NINDS NIH HHS/United States ; NS067563/NS/NINDS NIH HHS/United States ; AT005378/AT/NCCIH NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/adverse effects ; Bone Marrow Transplantation ; Citrobacter rodentium/*immunology ; Colony Count, Microbial ; Disease Susceptibility ; Dysbiosis/chemically induced/genetics/*immunology/microbiology ; Enterobacteriaceae Infections/genetics/*immunology/microbiology/pathology ; Fecal Microbiota Transplantation ; Gene Expression ; Germ-Free Life/*immunology ; Interleukins/biosynthesis/immunology ; Lymphocytes/drug effects/immunology/microbiology ; Mice ; Mice, Knockout ; Microbiota/drug effects/immunology ; Receptors, Calcitriol/*deficiency/genetics/immunology ; Interleukin-22 ; }, abstract = {Vitamin D receptor (VDR) knockout (KO) mice had fewer Citrobacter rodentium in the feces than wild-type (WT) mice and the kinetics of clearance was faster in VDR KO than WT mice. VDR KO mice had more interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) and more antibacterial peptides than WT mice. The increased ILCs in the VDR KO mice was a cell-autonomous effect of VDR deficiency on ILC frequencies. Bone marrow (BM) transplantation from VDR KO mice into WT resulted in higher ILCs and colonization resistance of the WT mice. Disruption of the gut microbiota using antibiotics in VDR KO mice reversed colonization resistance to C. rodentium infection. Confirming the role of the microbiota in the colonization resistance of VDR KO mice, transfer of the VDR KO microbiota to WT germ-free mice resulted in colonization resistance. Once colonization resistance was overcome, VDR KO mice had increased susceptibility to C. rodentium. VDR expression is a regulator of ILC frequencies, IL-22, dysbiosis, and C. rodentium susceptibility.}, }
@article {pmid25314344, year = {2014}, author = {To, KB and Napolitano, LM}, title = {Clostridium difficile infection: update on diagnosis, epidemiology, and treatment strategies.}, journal = {Surgical infections}, volume = {15}, number = {5}, pages = {490-502}, doi = {10.1089/sur.2013.186}, pmid = {25314344}, issn = {1557-8674}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*diagnosis/epidemiology/*therapy ; Humans ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) has increased in incidence and severity over the past quarter century, and is now considered a major cause of healthcare-associated infections.<br><br>METHODS: Review of the pertinent English-language medical literature.<br><br>RESULTS: There has been a substantial change in the management of CDI. The emergence of the NAP1/BI/O27 strain in the early to mid-2000s has been associated with more severe forms of CDI. The pathophysiology, epidemiology, clinical manifestations and diagnosis, as well as new strategies for medical and surgical management are discussed in this review.<br><br>CONCLUSIONS: Clostridium difficile infection can range from benign diarrhea to severe disease associated with substantial morbidity and mortality. Treatment modalities vary based on disease severity and timing of onset. The mainstay of medical treatment remains metronidazole and oral/rectal vancomycin. New management strategies are evolving, including adjunctive treatments such as monoclonal antibodies, vaccination, and fecal transplant. In patients with severe disease or clinical deterioration, early surgical consultation for total colectomy or loop ileostomy may be life-saving. Infection control measures are vital to mitigating the spread of CDI.}, }
@article {pmid25300242, year = {2015}, author = {Gundling, F and Tiller, M and Agha, A and Schepp, W and Iesalnieks, I}, title = {Successful autologous fecal transplantation for chronic diversion colitis.}, journal = {Techniques in coloproctology}, volume = {19}, number = {1}, pages = {51-52}, pmid = {25300242}, issn = {1128-045X}, mesh = {Aged ; Biological Therapy/*methods ; Colitis/*etiology/*therapy ; Colostomy/*adverse effects ; Feces/*microbiology ; Female ; Humans ; Microbiota ; Transplantation, Autologous/methods ; }, }
@article {pmid25294262, year = {2014}, author = {Gomollón, F}, title = {[Developments in the treatment of inflammatory bowel disease: 2014 overview].}, journal = {Gastroenterologia y hepatologia}, volume = {37 Suppl 3}, number = {}, pages = {14-21}, doi = {10.1016/S0210-5705(14)70079-2}, pmid = {25294262}, issn = {0210-5705}, mesh = {Humans ; Inflammatory Bowel Diseases/drug therapy/*therapy ; }, abstract = {The way we treat inflammatory bowel disease is rapidly changing. Biologics have accounted for the biggest change in recent years, and they are being used on a more regular basis, on more indications and at earlier stages. However, primary response failure and, above all, secondary response failure and cost represent serious limitations for their use. Combination immunosuppressant therapy, individualization depending on levels and response, increasing compliance and a more suitable choice of cases can all enhance effectiveness. However in many cases, new alternatives will be necessary. Recently, 2 new antibodies have been approved: golimumab is a new option for ulcerative colitis and with another more selective mechanism of action; vedolizumab could be useful for ulcerative colitis as well as Crohn's disease. Ustekinumab is an alternative treatment option for refractory Crohn's disease. In addition to biologics, autologous bone marrow transplants and, anecdotally, the use of immunoglobulins have been suggested as alternatives in some carefully selected cases. Although effective for Clostridium difficile infection, the potential role of fecal transplants in inflammatory bowel disease is still to be determined, without initially observing very promising results. The use of probiotics has not produced significant positive results.}, }
@article {pmid25291136, year = {2014}, author = {Cammarota, G and Ianiro, G and Bibbò, S and Gasbarrini, A}, title = {Fecal microbiota transplantation: a new old kid on the block for the management of gut microbiota-related disease.}, journal = {Journal of clinical gastroenterology}, volume = {48 Suppl 1}, number = {}, pages = {S80-4}, doi = {10.1097/MCG.0000000000000244}, pmid = {25291136}, issn = {1539-2031}, mesh = {Animals ; Biological Therapy/*methods ; Clostridioides difficile/pathogenicity ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/therapy ; Feces/*microbiology ; Humans ; Immune System Diseases/diagnosis/microbiology/therapy ; Inflammatory Bowel Diseases/diagnosis/microbiology/therapy ; Intestines/*microbiology ; Metabolic Diseases/diagnosis/microbiology/therapy ; Nervous System Diseases/diagnosis/microbiology/therapy ; Treatment Outcome ; }, abstract = {Gut microbiota is deeply involved in the regulation of both health and disease within our body. The restoration of a healthy gut microbiota is, therefore, a main clinical target in the management of diseases associated with its disruption. Fecal microbiota transplantation (FMT) is an old therapy that has recently been rediscovered, having proved a clear efficacy against recurrent Clostridium difficile infection. By restoring the altered gut microbiota in a substantial and durable manner, FMT is considered a cutting-edge promising option for the treatment of disease that recognize the alteration of the gut microbiota as having a pathogenic role. FMT has shown interesting (even if uncertain) results in diseases such as metabolic syndrome and inflammatory bowel diseases. Moreover, the definition of a standard procedural protocol for each specific disease, as well as exhaustive studies about the relationship between donor's microbiota composition and clinical results, will certainly improve the therapeutic potential of FMT. Both the application of cutting-edge technologies for the assessment of gut microbiota composition (such as metagenomics) and the development of well-designed, large randomized trials are needed to put such perspectives into practice.}, }
@article {pmid25289916, year = {2014}, author = {Lee, JR and Muthukumar, T and Dadhania, D and Toussaint, NC and Ling, L and Pamer, E and Suthanthiran, M}, title = {Gut microbial community structure and complications after kidney transplantation: a pilot study.}, journal = {Transplantation}, volume = {98}, number = {7}, pages = {697-705}, pmid = {25289916}, issn = {1534-6080}, support = {R37 AI051652/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K08-DK087824/DK/NIDDK NIH HHS/United States ; KL2 TR000458/TR/NCATS NIH HHS/United States ; KL2-TR000458/TR/NCATS NIH HHS/United States ; R37AI051652/AI/NIAID NIH HHS/United States ; K08 DK087824/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Diarrhea ; Enterococcus/isolation &amp; purification ; Feces/microbiology ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Intestines/*microbiology ; Kidney Failure, Chronic/complications/*surgery ; Kidney Transplantation/*adverse effects ; Linear Models ; Male ; *Microbiota ; Middle Aged ; Pilot Projects ; Polymerase Chain Reaction ; Prospective Studies ; Proteobacteria/isolation &amp; purification ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The gut microbiome plays a role in the regulation of the immune system.<br><br>METHODS: We prospectively enrolled 26 kidney transplant recipients and collected serial fecal specimens (N=85) during the first three months of transplantation. We characterized bacterial composition by polymerase chain reaction amplification of the 16S rRNA V4-V5 variable region and deep sequencing using the Illumina MiSeq platform.<br><br>RESULTS: An increase in the relative abundance of Proteobacteria was observed in the posttransplantation specimens compared to pretransplantation specimens (P=0.04, Wilcoxon signed-rank test). In patients with posttransplant diarrhea, the mean(&#xb1;standard deviation [SD]) Shannon diversity index was lower in those with diarrhea (N=6) than those without diarrhea (N=9) (2.5&#xb1;0.3 vs. 3.4&#xb1;0.8; P = 0.02, Wilcoxon rank-sum test). Principal coordinate analysis showed clear separation between the two groups, and linear discriminant analysis effect size (LEfSe) method revealed that Bacteroides, Ruminococcus, Coprococcus, and Dorea were significantly lower in the patients with diarrhea. Principal coordinate analysis also showed clear separation between the acute rejection (AR) group (N=3) and the no AR group (N=23) and the LEfSe method revealed significant differences between the two groups. Fecal abundance of Enterococcus was associated with Enterococcus urinary tract infection (UTI). The median Enterococcus fecal abundance was 24% (range, 8%-95%) in the three patients with Enterococcus UTI compared to 0% in the 23 patients without Enterococcus UTI (interquartile range, 0.00%-0.08%) (P=0.005, Wilcoxon rank-sum test).<br><br>CONCLUSION: Our pilot study identified significant alterations in the gut microbiota after kidney transplantation. Moreover, distinct microbiota structures were observed in allograft recipients with posttransplant diarrhea, AR, and Enterococcus UTI.}, }
@article {pmid25282930, year = {2014}, author = {Storr, M}, title = {[Fecal microbiome transfer helps in clostridium infections].}, journal = {MMW Fortschritte der Medizin}, volume = {156}, number = {15}, pages = {35}, pmid = {25282930}, issn = {1438-3276}, mesh = {Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Inflammatory Bowel Diseases/complications/therapy ; Microbiota/*physiology ; Prognosis ; *Transplantation ; }, }
@article {pmid25275120, year = {2014}, author = {Vega, E and Donaldson, E and Huynh, J and Barclay, L and Lopman, B and Baric, R and Chen, LF and Vinjé, J}, title = {RNA populations in immunocompromised patients as reservoirs for novel norovirus variants.}, journal = {Journal of virology}, volume = {88}, number = {24}, pages = {14184-14196}, pmid = {25275120}, issn = {1098-5514}, support = {R01 AI056351/AI/NIAID NIH HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; AI 056351),/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Aged ; Caliciviridae Infections/*virology ; Diarrhea/*virology ; Evolution, Molecular ; Feces/virology ; Female ; *Genetic Variation ; Genotype ; Humans ; *Immunocompromised Host ; Infant ; Male ; Molecular Sequence Data ; Norovirus/*classification/*genetics/isolation &amp; purification ; RNA, Viral/*genetics ; Sequence Analysis, DNA ; }, abstract = {UNLABELLED: Noroviruses are the leading cause of acute gastroenteritis outbreaks worldwide. The majority of norovirus outbreaks are caused by genogroup II.4 (GII.4). Novel GII.4 strains emerge every 2 to 4 years and replace older variants as the dominant norovirus. Novel variants emerge through a combination of recombination, genetic drift, and selection driven by population immunity, but the exact mechanism of how or where is not known. We detected two previously unknown novel GII.4 variants, termed GII.4 UNK1 and GII.4 UNK2, and a diverse norovirus population in fecal specimens from immunocompromised individuals with diarrhea after they had undergone bone marrow transplantation. We hypothesized that immunocompromised individuals can serve as reservoirs for novel norovirus variants. To test our hypothesis, metagenomic analysis of viral RNA populations was combined with a full-genome bioinformatic analysis of publicly available GII.4 norovirus sequences from 1974 to 2014 to identify converging sites. Variable sites were proportionally more likely to be within two amino acids (P < 0.05) of positively selected sites. Further analysis using a hypergeometric distribution indicated that polymorphic site distribution was random and its proximity to positively selected sites was dependent on the size of the norovirus genome and the number of positively selected sites.In conclusion, random mutations may have a positive impact on driving norovirus evolution, and immunocompromised individuals could serve as potential reservoirs for novel GII.4 strains.<br><br>IMPORTANCE: Norovirus is the most common cause of viral gastroenteritis in the United States. Every 2 to 3 years novel norovirus variants emerge and replace dominant strains. The continual emergence of novel noroviruses is believed to be caused by a combination of genetic drift, population immunity, and recombination, but exactly how this emergence occurs remains unknown. In this study, we identified two novel GII.4 variants in immunocompromised bone marrow transplant patients. Using metagenomic and bioinformatic analysis, we showed that most genetic polymorphisms in the novel variants occur near 0 to 2 amino acids of positively selected sites, but the distribution of mutations was random; clustering of polymorphisms with positively selected sites was a result of genome size and number of mutations and positively selected sites. This study shows that immunocompromised patients can harbor infectious novel norovirus variants, and although mutations in viruses are random, they can have a positive effect on viral evolution.}, }
@article {pmid25274397, year = {2014}, author = {Raoult, D}, title = {Faecal transplantation and infectious diseases practitioners.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {20}, number = {11}, pages = {1097}, doi = {10.1111/1469-0691.12790}, pmid = {25274397}, issn = {1469-0691}, mesh = {Biological Therapy/*methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; Cross Infection/*therapy ; Diarrhea/*therapy ; *Feces ; Humans ; }, }
@article {pmid25274251, year = {2014}, author = {Kump, PK and Krause, R and Allerberger, F and Högenauer, C}, title = {Faecal microbiota transplantation--the Austrian approach.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {20}, number = {11}, pages = {1106-1111}, doi = {10.1111/1469-0691.12801}, pmid = {25274251}, issn = {1469-0691}, mesh = {Austria ; Biological Therapy/*methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Cross Infection/microbiology/*therapy ; Diarrhea/microbiology/*therapy ; *Feces ; Guidelines as Topic ; Health Policy ; Humans ; }, abstract = {The intestinal microbiome is essential for maintaining human health and defending against intestinal pathogens. Alterations of the intestinal microbiota, also termed dysbiosis, play a pivotal role in the pathogenesis of various human diseases. Faecal microbiota transplantation (FMT) is aimed at correcting these alterations by delivering faecal microorganisms from a healthy person to the intestines of a patient. At present, recurrent Clostridium difficile infection is the only indication supported by solid scientific evidence, but many ongoing studies are investigating FMT in other dysbiosis-related diseases, such as inflammatory bowel disease. As there are no systematic methodological investigations, several questions about techniques, donor screening and safety issues remain. This shortage of evidence, especially on long-term safety concerns, is leading to worldwide controversy regarding the use of FMT. Regulations by healthcare authorities vary among different countries. This review reflects the Austrian situation and its FMT guidelines concerning indications, techniques and donor screening, recently developed by local scientific societies.}, }
@article {pmid25274035, year = {2014}, author = {Singh, R and Nieuwdorp, M and ten Berge, IJ and Bemelman, FJ and Geerlings, SE}, title = {The potential beneficial role of faecal microbiota transplantation in diseases other than Clostridium difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {20}, number = {11}, pages = {1119-1125}, doi = {10.1111/1469-0691.12799}, pmid = {25274035}, issn = {1469-0691}, mesh = {Biological Therapy/*methods ; *Feces ; Humans ; Inflammatory Bowel Diseases/*therapy ; Irritable Bowel Syndrome/*therapy ; Metabolic Syndrome/*therapy ; Randomized Controlled Trials as Topic ; }, abstract = {This review gives an outline of the indications for faecal microbiota transplantation (FMT) for diseases other than Clostridium difficile (C. difficile) infection. The remarkable efficacy of FMT against C. difficile infection has already been demonstrated. The use of FMT for other diseases, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and metabolic syndrome, is now being evaluated. The currently available data suggest that FMT might be beneficial for IBD (including ulcerative colitis and, to some extent, Crohn's disease), IBS, and insulin resistance. Several randomized clinical trials are currently being performed, and data are eagerly awaited. A new field of research for the implementation of FMT is the eradication of pathogenic and multiresistant enteric microorganisms. A few animal studies have been performed within this field, but hardly any research data from human studies are available at present.}, }
@article {pmid25273614, year = {2014}, author = {Kapel, N and Thomas, M and Corcos, O and Mayeur, C and Barbot-Trystram, L and Bouhnik, Y and Joly, F}, title = {Practical implementation of faecal transplantation.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {20}, number = {11}, pages = {1098-1105}, doi = {10.1111/1469-0691.12796}, pmid = {25273614}, issn = {1469-0691}, mesh = {Biological Therapy/*methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Cross Infection/microbiology/*therapy ; Diarrhea/microbiology/*therapy ; *Feces ; Humans ; Randomized Controlled Trials as Topic ; }, abstract = {Clostridium difficile infection is a leading cause of antibiotic-related and healthcare-related diarrhoea. In the past decade, faecal microbiota transplantation or transfer has attracted increasing interest as an effective treatment strategy for severe recurrent C. difficile infection, with a global success rate of >80%. However, experience with this procedure is limited by a lack of randomized trials supporting its efficacy and the lack of standardization of the procedure. This review will address the practical aspects of the protocol.}, }
@article {pmid25273480, year = {2014}, author = {Lagier, JC}, title = {Faecal microbiota transplantation: from practice to legislation before considering industrialization.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {20}, number = {11}, pages = {1112-1118}, doi = {10.1111/1469-0691.12795}, pmid = {25273480}, issn = {1469-0691}, mesh = {Biological Therapy/adverse effects/*methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Cross Infection/microbiology/*therapy ; Diarrhea/microbiology/*therapy ; Donor Selection ; *Feces ; France ; Humans ; Industry ; Recurrence ; United States ; }, abstract = {Recurrent Clostridium difficile infections constitute an important medical concern. Evidence has been provided showing that faecal microbiota transplantation is a more efficient treatment than antibiotics. Serious side effects are unusual, and acceptability is not an obstacle. Nevertheless, protocols are heterogeneous with respect to the selection of donors and the methodology used for the faecal transplantation. Regulations by both the Food and Drug Administration and the French authorities consider stool samples to be drugs, and suggest strict supervision in clinical trials. Donor screening by questionnaire or by blood and stool analysis, which is essential in eliminating pathogens or viruses before transplantation, is similar in different countries, with a few exceptions. The traceability of the faecal transplant and long-term follow-up of the patients in clinical trials are issues that may be difficult to organize. The use of frozen microbiota facilitates transplantation, and the nasogastric route seems to be at least as effective as other invasive methods and avoids the risk of anaesthesia. Synthetic microbiota is an approach that selects a mixture of bacteria, thereby eliminating the risk of transmissible disease; however, this approach is not yet evidence-based. The use of pills, which is currently being tested in clinical trials, will certainly be the starting point for the extensive use and wide industrialization of faecal microbiota transplantation.}, }
@article {pmid25267201, year = {2014}, author = {Gallian, P and Piquet, Y and Assal, A and Djoudi, R and Chiaroni, J and Izopet, J and Tiberghien, P}, title = {[Hepatitis E virus: Blood transfusion implications].}, journal = {Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine}, volume = {21}, number = {4-5}, pages = {173-177}, doi = {10.1016/j.tracli.2014.07.007}, pmid = {25267201}, issn = {1953-8022}, mesh = {Blood Donors ; Blood Safety/*standards ; Communicable Diseases, Emerging/epidemiology/prevention &amp; control ; Detergents ; Developing Countries ; *Donor Selection ; France/epidemiology ; Genotype ; Global Health ; Hepatitis Antibodies/*blood ; Hepatitis E/blood/diagnosis/*epidemiology/prevention &amp; control/transmission ; Hepatitis E virus/drug effects/genetics/immunology/isolation &amp; purification ; Humans ; Immunoglobulin G/*blood ; *Nucleic Acid Amplification Techniques ; Plasma/virology ; RNA, Viral/*blood ; Risk ; Seroepidemiologic Studies ; Solvents ; *Transfusion Reaction ; Viremia/diagnosis/epidemiology/transmission ; Virus Inactivation ; }, abstract = {Hepatitis E virus (HEV) is a non-enveloped RNA virus transmitted by the fecal-oral route. Autochthonous hepatitis E occurring in developed countries is caused by genotypes 3 and 4 and is a zoonotic infection. Humans are infected mostly after ingestion of undercooked meat from infected animals. Most HEV 3 and 4 infections are clinically inapparent. However, genotype 3 (HEV 3) can lead to chronic hepatitis in immuno-compromised patients such as organ-transplant recipients and patients with haematological malignancies. In Europe, HEV 3 is implicated in transfusion-transmitted HEV infection. In France, as observed in several European countries, prevalence of HEV RNA and specific IgG antibodies are high indicating that viral circulation is important. The systematic HEV NAT screening of blood donations used for preparation of solvent detergent plasma indicate that 1 to 2218 donation is infected by HEV RNA. The need or implementation's impacts of safety measures to prevent HEV transmission by blood transfusion are under reflexion by French's health authorities. The HEV NAT screening is the only available tool of prevention. Alternative strategies are under investigation including individual or mini pool NAT testing all or part of blood donations.}, }
@article {pmid25265462, year = {2015}, author = {de Castro, CG and Ganc, AJ and Ganc, RL and Petrolli, MS and Hamerschlack, N}, title = {Fecal microbiota transplant after hematopoietic SCT: report of a successful case.}, journal = {Bone marrow transplantation}, volume = {50}, number = {1}, pages = {145}, pmid = {25265462}, issn = {1476-5365}, mesh = {Allografts ; Anti-Bacterial Agents/*administration &amp; dosage ; *Clostridioides difficile ; *Enterocolitis, Pseudomembranous/drug therapy/etiology ; *Feces ; Female ; *Hematopoietic Stem Cell Transplantation ; Humans ; Metronidazole ; *Microbiota ; Middle Aged ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Vancomycin/*administration &amp; dosage ; }, }
@article {pmid25262872, year = {2014}, author = {DePeters, EJ and George, LW}, title = {Rumen transfaunation.}, journal = {Immunology letters}, volume = {162}, number = {2 Pt A}, pages = {69-76}, doi = {10.1016/j.imlet.2014.05.009}, pmid = {25262872}, issn = {1879-0542}, mesh = {Abomasum/surgery ; Animals ; *Catheterization ; Cattle ; Dyspepsia/etiology/*therapy ; Fermentation ; Humans ; Postoperative Complications/*therapy ; Practice Guidelines as Topic ; Plastic Surgery Procedures/veterinary ; Rumen/*microbiology/surgery ; Stomach Diseases/*surgery/veterinary ; }, abstract = {The aim of this invited mini-review is to summarize the rumen transfaunation literature. Rumen transfaunation using the cud from a healthy donor animal to treat a sick recipient animal was practiced long before our understanding of rumen microorganisms. Around the mid-1900 s, scientists began to explore the benefits of rumen transfaunation and the associated microbial populations. Rumen transfaunation has been used clinically to treat indigestion and to enhance the return of normal rumen function following surgical correction of a left-displaced abomasum. Rumen transfaunation was also used to introduce unique rumen microorganisms into animals that were exposed to toxic compounds in plants. Rumen liquor contains chemical constituents that likely contribute to the beneficial effects of re-establishing a normal reticulo-rumen anaerobic fermentation. Recommendations for collecting rumen fluid, storage and volumes transferred are discussed. Rumen transfaunation is a common practice to treat indigestion on dairy and livestock operations. The support of a healthy microbial community in the digestive tract is also used for humans. Fecal microbiota transplantation has been used to treat digestive disorders in humans. Rumen transfaunation, although not widely studied with respect to mode of action, is an effective, practical, and easy method to treat simple indigestion of ruminants.}, }
@article {pmid25261078, year = {2014}, author = {Altomare, DF}, title = {Comments to "perianal injectable bulking agents as treatment for faecal incontinence in adults".}, journal = {Techniques in coloproctology}, volume = {18}, number = {11}, pages = {1139-1140}, pmid = {25261078}, issn = {1128-045X}, mesh = {Biocompatible Materials/*administration &amp; dosage ; Fecal Incontinence/*therapy ; Humans ; }, }
@article {pmid25253977, year = {2014}, author = {Kim, JE and Gweon, TG and Yeo, CD and Cho, YS and Kim, GJ and Kim, JY and Kim, JW and Kim, H and Lee, HW and Lim, T and Ham, H and Oh, HJ and Lee, Y and Byeon, J and Park, SS}, title = {A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation.}, journal = {World journal of gastroenterology}, volume = {20}, number = {35}, pages = {12687-12690}, pmid = {25253977}, issn = {2219-2840}, mesh = {Aged, 80 and over ; Anti-Bacterial Agents/*adverse effects ; Biological Therapy/*methods ; Clostridioides difficile/*pathogenicity ; Colon/*microbiology ; *Duodenoscopy ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*therapy ; Feces/*microbiology ; Humans ; Male ; Pneumonia, Bacterial/diagnosis/microbiology/*therapy ; Respiratory Distress Syndrome/diagnosis/microbiology/*therapy ; Sigmoidoscopy ; Time Factors ; Treatment Outcome ; }, abstract = {Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia. Clostridium difficile infection (CDI) is a common nosocomial diarrheal disease. Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI. The use of broad-spectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome. Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI. Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.}, }
@article {pmid25250608, year = {2014}, author = {Merchant, N and Boudana, D and Willoughby, L and Lin, J and Rehou, S and Shahrokhi, S and Jeschke, MG}, title = {Management of adult patients with buttock and perineal burns: The Ross Tilley Burn Centre experience.}, journal = {The journal of trauma and acute care surgery}, volume = {77}, number = {4}, pages = {640-648}, pmid = {25250608}, issn = {2163-0763}, support = {R01 GM087285/GM/NIGMS NIH HHS/United States ; 123336/CAPMC/CIHR/Canada ; R01GM087285-01/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Algorithms ; Allografts ; Burns/complications/physiopathology/*surgery ; Buttocks/*injuries ; Fecal Incontinence/etiology/therapy ; Female ; Humans ; Male ; Middle Aged ; Perineum/*injuries ; Retrospective Studies ; Skin Diseases, Infectious/prevention &amp; control ; Skin Transplantation ; Treatment Outcome ; *Wound Healing/physiology ; Wound Infection/prevention &amp; control ; }, abstract = {BACKGROUND: Perineal and buttock burns are challenging wounds to heal for several reasons because of the contamination risk and shear stress that is always present. Because of the nature of the wound bed, pathogens can have ready access to create systemic infections and complications. Prolonged healing times also delay the recovery for patients and add to their discomfort and psychological stress from the injury. The ideal treatment approach is not well defined, and the aims of this study were to conduct a literature review of current treatment suggestions and to look at our own patient population to determine how our center treated these challenging patients.<br><br>METHODS: This is a retrospective review of all patients treated between 2010 and 2013 at our center. Patients that received care for burns to the perineum or buttocks were evaluated. Mortalities within 24 hours of admission and transfers before completion of their care were excluded. All patients older than 18 years were included in the study. The primary outcome studied was a cause for graft revision. Secondary outcomes included benefits and risks of fecal management devices, risk of infection, and mortality.<br><br>RESULTS: The literature review did not show consensus on how to best manage this patient population. Our results however demonstrated that patients treated with the fecal management device Flexi-seal (Convatec, Skillman, NJ) were at increased risk of developing an infection involving an enteric pathogen and requiring revision procedures. The patient population that was treated with this device was also older and had larger burns. The patients within this group that were treated initially with allograft required fewer revisions when compared with patients that received autograft in this group (23% vs. 34%, p > 0.05).<br><br>CONCLUSION: After our data and the literature had been reviewed, the lack of evidence-based treatment protocols led us to create recommendations for burn surgeons with regard to the initial management of this complicated area. Certain key features include avoiding autograft at the primary excision if they have an increased revised Baux score and minimizing the amount of liquid stool contaminating the wound bed to increase success.<br><br>LEVEL OF EVIDENCE: Epidemiologic study, level IV. Therapeutic study, level V.}, }
@article {pmid25249523, year = {2015}, author = {Abravanel, F and Lhomme, S and Rostaing, L and Kamar, N and Izopet, J}, title = {Protracted fecal shedding of HEV during ribavirin therapy predicts treatment relapse.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {60}, number = {1}, pages = {96-99}, doi = {10.1093/cid/ciu742}, pmid = {25249523}, issn = {1537-6591}, mesh = {Adult ; Aged ; Antiviral Agents/*therapeutic use ; Feces/*virology ; Female ; Hepatitis E/*drug therapy/*virology ; Hepatitis E virus/*isolation &amp; purification ; Humans ; Male ; Middle Aged ; Organ Transplantation ; Recurrence ; Ribavirin/*therapeutic use ; Treatment Outcome ; *Virus Shedding ; }, abstract = {Twenty-four solid-organ-transplant recipients with chronic hepatitis E virus (HEV) infections were given ribavirin therapy for 3 months. All the patients with protracted fecal HEV shedding during treatment suffered a relapse. Monitoring HEV fecal excretion could be used to determine the optimal duration of ribavirin therapy.}, }
@article {pmid25248287, year = {2014}, author = {Cheng, VC and Chen, JH and Tai, JW and Wong, SC and Poon, RW and Hung, IF and To, KK and Chan, JF and Ho, PL and Lo, CM and Yuen, KY}, title = {Decolonization of gastrointestinal carriage of vancomycin-resistant Enterococcus faecium: case series and review of literature.}, journal = {BMC infectious diseases}, volume = {14}, number = {}, pages = {514}, pmid = {25248287}, issn = {1471-2334}, mesh = {Aged ; Anti-Bacterial Agents/therapeutic use ; Carrier State/microbiology ; Cross Infection/drug therapy/microbiology/*prevention &amp; control ; Enterococcus faecium/drug effects/*growth &amp; development ; Female ; Gastrointestinal Tract/*microbiology ; Gram-Positive Bacterial Infections/drug therapy/microbiology/*prevention &amp; control ; Hospitalization ; Humans ; Male ; Middle Aged ; *Vancomycin Resistance ; }, abstract = {BACKGROUND: Prolonged asymptomatic carriage of vancomycin-resistant enterococci (VRE) in the gastrointestinal tract and the lack of effective decolonization regimen perpetuate the endemicity of VRE in the healthcare settings.<br><br>CASE PRESENTATION: We report a regimen for decolonization of gastrointestinal carriage of VRE by a combination of environmental disinfection, patient isolation, bowel preparation to wash-out the fecal bacterial population using polyethylene glycol, a five-day course of oral absorbable linezolid and non-absorbable daptomycin to suppress any remaining VRE, and subsequent oral Lactobacillus rhamnosus GG to maintain the colonization resistance in four patients, including two patients with end-stage liver cirrhosis, one patient with complication post liver transplant, and one patient with complicated infective endocarditis. All patients had clearance of VRE immediately after decolonization, and 3 of them remained VRE-free for 23 to 137 days of hospitalization, despite subsequent use of intravenous broad-spectrum antibiotics without anti-VRE activity.<br><br>CONCLUSION: This strategy should be further studied in settings of low VRE endemicity with limited isolation facilities.}, }
@article {pmid25239307, year = {2014}, author = {van der Mark, VA and de Waart, DR and Ho-Mok, KS and Tabbers, MM and Voogt, HW and Oude Elferink, RP and Knisely, AS and Paulusma, CC}, title = {The lipid flippase heterodimer ATP8B1-CDC50A is essential for surface expression of the apical sodium-dependent bile acid transporter (SLC10A2/ASBT) in intestinal Caco-2 cells.}, journal = {Biochimica et biophysica acta}, volume = {1842}, number = {12 Pt A}, pages = {2378-2386}, doi = {10.1016/j.bbadis.2014.09.003}, pmid = {25239307}, issn = {0006-3002}, mesh = {Adenosine Triphosphatases/chemistry/genetics/*metabolism ; Bile Acids and Salts/metabolism ; Biological Transport/genetics ; Blotting, Western ; Caco-2 Cells ; Cell Membrane/metabolism ; Cholestasis, Intrahepatic/genetics/metabolism ; Feces/chemistry ; Humans ; Intestinal Mucosa/metabolism ; Membrane Proteins/chemistry/genetics/*metabolism ; Mutation ; Organic Anion Transporters, Sodium-Dependent/*metabolism ; Protein Multimerization ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; Symporters/*metabolism ; Taurocholic Acid/metabolism/pharmacokinetics ; }, abstract = {Deficiency of the phospholipid flippase ATPase, aminophospholipid transporter, class I, type 8B, member 1 (ATP8B1) causes progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis type 1 (BRIC1). Apart from cholestasis, many patients also suffer from diarrhea of yet unknown etiology. Here we have studied the hypothesis that intestinal ATP8B1 deficiency results in bile salt malabsorption as a possible cause of PFIC1/BRIC1 diarrhea. Bile salt transport was studied in ATP8B1-depleted intestinal Caco-2 cells. Apical membrane localization was studied by a biotinylation approach. Fecal bile salt and electrolyte contents were analyzed in stool samples of PFIC1 patients, of whom some had undergone biliary diversion or liver transplantation. Bile salt uptake by the apical sodium-dependent bile salt transporter solute carrier family 10 (sodium/bile acid cotransporter), member 2 (SLC10A2) was strongly impaired in ATP8B1-depleted Caco-2 cells. The reduced SLC10A2 activity coincided with strongly reduced apical membrane localization, which was caused by impaired apical membrane insertion of SLC10A2. Moreover, we show that endogenous ATP8B1 exists in a functional heterodimer with transmembrane protein 30A (CDC50A) in Caco-2 cells. Analyses of stool samples of post-transplant PFIC1 patients demonstrated that bile salt content was not changed, whereas sodium and chloride concentrations were elevated and potassium levels were decreased. The ATP8B1-CDC50A heterodimer is essential for the apical localization of SLC10A2 in Caco-2 cells. Diarrhea in PFIC1/BRIC1 patients has a secretory origin to which SLC10A2 deficiency may contribute. This results in elevated luminal bile salt concentrations and consequent enhanced electrolyte secretion and/or reduced electrolyte resorption.}, }
@article {pmid25232572, year = {2014}, author = {Moayyedi, P and Marshall, JK and Yuan, Y and Hunt, R}, title = {Canadian Association of Gastroenterology position statement: fecal microbiota transplant therapy.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {28}, number = {2}, pages = {66-68}, pmid = {25232572}, issn = {2291-2797}, mesh = {Canada ; Feces/*microbiology ; Gastroenterology/*methods ; Humans ; Microbiota ; Societies, Medical ; Transplantation/*methods ; }, }
@article {pmid25232246, year = {2014}, author = {Carrière, J and Darfeuille-Michaud, A and Nguyen, HT}, title = {Infectious etiopathogenesis of Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {20}, number = {34}, pages = {12102-12117}, pmid = {25232246}, issn = {2219-2840}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacteria/drug effects/*growth &amp; development/immunology ; Crohn Disease/diagnosis/genetics/immunology/*microbiology/therapy ; Dysbiosis ; Host-Pathogen Interactions ; Humans ; Intestines/immunology/*microbiology ; Microbiota ; Probiotics/therapeutic use ; Risk Factors ; Treatment Outcome ; }, abstract = {Important advances during the last decade have been made in understanding the complex etiopathogenesis of Crohn's disease (CD). While many gaps in our knowledge still exist, it has been suggested that the etiology of CD is multifactorial including genetic, environmental and infectious factors. The most widely accepted theory states that CD is caused by an aggressive immune response to infectious agents in genetically predisposed individuals. The rise of genome-wide association studies allowed the identification of loci and genetic variants in several components of host innate and adaptive immune responses to microorganisms in the gut, highlighting an implication of intestinal microbiota in CD etiology. Moreover, numerous independent studies reported a dysbiosis, i.e., a modification of intestinal microbiota composition, with an imbalance between the abundance of beneficial and harmful bacteria. Although microorganisms including viruses, yeasts, fungi and bacteria have been postulated as potential CD pathogens, based on epidemiological, clinicopathological, genetic and experimental evidence, their precise role in this disease is not clearly defined. This review summarizes the current knowledge of the infectious agents associated with an increased risk of developing CD. Therapeutic approaches to modulate the intestinal dysbiosis and to target the putative CD-associated pathogens, as well as their potential mechanisms of action are also discussed.}, }
@article {pmid25231862, year = {2014}, author = {Suez, J and Korem, T and Zeevi, D and Zilberman-Schapira, G and Thaiss, CA and Maza, O and Israeli, D and Zmora, N and Gilad, S and Weinberger, A and Kuperman, Y and Harmelin, A and Kolodkin-Gal, I and Shapiro, H and Halpern, Z and Segal, E and Elinav, E}, title = {Artificial sweeteners induce glucose intolerance by altering the gut microbiota.}, journal = {Nature}, volume = {514}, number = {7521}, pages = {181-186}, pmid = {25231862}, issn = {1476-4687}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Aspartame/adverse effects ; Body Weight/drug effects ; Diet, High-Fat ; Dietary Fats/pharmacology ; Feces/microbiology ; Female ; Gastrointestinal Tract/*drug effects/*microbiology ; Germ-Free Life ; Glucose/metabolism ; Glucose Intolerance/*chemically induced/metabolism/*microbiology ; Humans ; Male ; Metabolic Syndrome/chemically induced/metabolism/microbiology ; Mice ; Mice, Inbred C57BL ; Microbiota/*drug effects ; Saccharin/administration &amp; dosage/adverse effects ; Sucrose/adverse effects/analogs &amp; derivatives ; Sweetening Agents/*adverse effects ; Waist-Hip Ratio ; }, abstract = {Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage.}, }
@article {pmid25231539, year = {2014}, author = {Schoster, A and Weese, JS and Guardabassi, L}, title = {Probiotic use in horses - what is the evidence for their clinical efficacy?.}, journal = {Journal of veterinary internal medicine}, volume = {28}, number = {6}, pages = {1640-1652}, pmid = {25231539}, issn = {1939-1676}, mesh = {Animals ; Gastrointestinal Tract/drug effects/microbiology ; Horse Diseases/drug therapy/microbiology/*prevention &amp; control ; Horses/microbiology ; Microbiota/drug effects ; Probiotics/*therapeutic use ; }, abstract = {The gastrointestinal microbiota is extremely important for human and animal health. Investigations into the composition of the microbiota and its therapeutic modification have received increasing interest in human and veterinary medicine. Probiotics are a way of modifying the microbiota and have been tested to prevent and treat diseases. Probiotics are proposed to exert their beneficial effects through various pathways. Production of antimicrobial compounds targeting intestinal pathogens, general immune stimulation, and colonization resistance are among these mechanisms. Despite widespread availability and use, scientific, peer-reviewed evidence behind commercial probiotic formulations in horses is limited. Additionally, quality control of commercial over-the-counter products is not tightly regulated. Although promising in vitro results have been achieved, in vivo health benefits have been more difficult to prove. Whether the ambiguous results are caused by strain selection, dosage selection or true lack of efficacy remains to be answered. Although these limitations exist, probiotics are increasingly used because of their lack of severe adverse effects, ease of administration, and low cost. This review summarizes the current evidence for probiotic use in equine medicine. It aims to provide veterinarians with evidence-based information on when and why probiotics are indicated for prevention or treatment of gastrointestinal disease in horses. The review also outlines the current state of knowledge on the equine microbiota and the potential of fecal microbial transplantation, as they relate to the topic of probiotics.}, }
@article {pmid25227298, year = {2014}, author = {Kahn, SA and Goeppinger, SR and Rubin, DT}, title = {Fecal microbiota transplantation: an interest in IBD?.}, journal = {Nestle Nutrition Institute workshop series}, volume = {79}, number = {}, pages = {101-114}, doi = {10.1159/000360715}, pmid = {25227298}, issn = {1664-2155}, mesh = {Clostridium Infections/therapy ; Feces/*microbiology ; Humans ; Inflammatory Bowel Diseases/*microbiology/*therapy ; *Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) is a targeted microbiome-based therapy that has garnered a great deal of attention from the scientific, clinical, and lay communities. An increasing number of studies have demonstrated that FMT is a highly effective therapy for recurrent/refractory Clostridium difficile infection and appears safe in the short term. Uncontrolled reports suggest the possibility of benefit in a select group of IBD patients, but there is quite limited information so far. FMT for IBD raises significant issues and concerns that warrant further systematic investigation. In this review, we discuss the background and rationale for this innovative therapy, the current knowledge for FMT in IBD, the logistical issues, and the important issues regarding ethics, social acceptability, and regulation.}, }
@article {pmid25227296, year = {2014}, author = {Wu, GD}, title = {Diet, the gut microbiome and the metabolome in IBD.}, journal = {Nestle Nutrition Institute workshop series}, volume = {79}, number = {}, pages = {73-82}, doi = {10.1159/000360686}, pmid = {25227296}, issn = {1664-2155}, support = {R01 GM103591/GM/NIGMS NIH HHS/United States ; }, mesh = {*Diet ; *Feeding Behavior ; Humans ; Inflammatory Bowel Diseases/*microbiology/therapy ; Intestines/*microbiology ; *Metabolome ; *Microbiota ; }, abstract = {The human gut contains a vast number of microorganisms known collectively as the gut microbiota. Despite its importance in maintaining the health of the host, growing evidence suggests the gut microbiota may also be an important factor in the pathogenesis of various diseases, a number of which have shown a rapid increase in incidence over the past few decades. In some of these diseases, such as inflammatory bowel disease (IBD), the microbiota is dysbiotic with an abnormal community structure and decrease in diversity. If the dysbiotic microbiota plays a role in disease pathogenesis, interventions that modify its composition to make it more similar to the microbiota observed in health, might be a strategy to treat certain disease processes. Indeed, the high-level efficacy of fecal microbiota transplantation in the treatment of refractory Clostridia difficile infection supports this notion as proof-of-principle. The composition of the microbiota can be influenced by many factors including age, genetics, host environment, and diet. With respect to the later, diet has an impact upon both the composition and function of the microbiota. There are epidemiologic data associating diet with the development of IBD as well as evidence that diet can influence both the form and function of the microbiome in a manner that impacts upon the development of intestinal inflammation. Based on this evidence, studies are now underway to examine the effect of defined formula diets, an effective therapeutic modality in Crohn's disease, on both the gut microbiome and its metabolome as a therapeutic probe with the hope of better defining the 'healthy' diet in patients with IBD.}, }
@article {pmid25226597, year = {2014}, author = {Bhadauria, D and Mahapatra, A and Singh, A and Kaul, A and Prasad, N and Sharma, RK and Lal, H and Mohindra, S}, title = {Severe anemia, hemoptysis, and melena with rapidly crescentic glomerulonephritis.}, journal = {The Journal of rheumatology}, volume = {41}, number = {9}, pages = {1893-1894}, doi = {10.3899/jrheum.140217}, pmid = {25226597}, issn = {1499-2752}, mesh = {Anemia/*complications ; Glomerulonephritis/*complications ; Hemoptysis/*complications ; Humans ; Klippel-Trenaunay-Weber Syndrome/*complications ; Male ; Melena/*complications ; Middle Aged ; }, }
@article {pmid25226084, year = {2015}, author = {Fu, G and Wang, D and Qin, B and Xiang, J and Qi, J and Li, P and Zhu, Q and Liu, X and Zhu, J and Gu, LQ}, title = {Modified classification and repair of perineal soft tissue injuries associated with open pelvic fractures.}, journal = {Journal of reconstructive microsurgery}, volume = {31}, number = {1}, pages = {12-19}, doi = {10.1055/s-0034-1386616}, pmid = {25226084}, issn = {1098-8947}, mesh = {China ; Clinical Protocols ; Female ; Follow-Up Studies ; Fracture Fixation/*methods ; Fractures, Open/classification/complications/*surgery ; Humans ; Injury Severity Score ; Male ; Pelvic Bones/*injuries/surgery ; Perineum/*injuries/surgery ; Rectum/*injuries/surgery ; Retrospective Studies ; Soft Tissue Injuries/classification/etiology/*surgery ; Surgical Flaps ; Treatment Outcome ; Wound Healing ; }, abstract = {BACKGROUND: This study describes a modified classification and management protocol for perineal soft tissue injuries associated with pelvic fractures.<br><br>METHODS: A total of 11 patients with perineal soft tissue injuries associated with open pelvic fractures were studied retrospectively. The patients were classified into three types based on the area of defect: type A (urogenital zone), type B (anal zone), and type C (both urogenital and anal zones). Each type included the following subclasses: A1 (without urethra injuries), A2 (with urethra injuries), B1 (without anorectal injuries), B2 (with anorectal injuries), C1 (with types A1 and B1), C2 (with types A2 and B1), C3 (with types A1 and B2), and C4 (with types A2 and B2). The management protocol was planned according to the individual classifications. Protocol A1 (for type A1) involved skin graft or myocutaneous flap transplantation. Protocol A2 (for type A2) involved the same protocol combined with urine diversion. Protocol B1 (for type B1) involved skin graft or myocutaneous flap transplantation. Protocol B2 (for type B2) involved the same management combined with fecal diversion. Protocol C involved the correspondent protocol used for each subtype of type C.<br><br>RESULTS: Out of the 11 patients, there were 5, 3, and 3 cases of types A, B, and C, respectively. One patient died due to sepsis, and the wounds of the remaining patients healed well. No anal incontinence had occurred.<br><br>CONCLUSIONS: Perineal soft tissue injuries associated with pelvic fractures can be classified into three types, and the management protocol can be planned according to the classification.}, }
@article {pmid25223604, year = {2014}, author = {Colman, RJ and Rubin, DT}, title = {Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {8}, number = {12}, pages = {1569-1581}, pmid = {25223604}, issn = {1876-4479}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; UL1 TR000430/TR/NCATS NIH HHS/United States ; P30DK42086/DK/NIDDK NIH HHS/United States ; }, mesh = {Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Intestinal Mucosa ; Microbiota ; Remission Induction ; Transplantation/*methods ; }, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) has gained interest as a novel treatment option for inflammatory bowel diseases (IBD). While publications describing FMT as therapy for IBD have more than doubled since 2012, research that investigates FMT treatment efficacy has been scarce. We conducted a systematic review and meta-analysis to evaluate the efficacy of FMT as treatment for patients with IBD.<br><br>METHODS: A systematic literature search was performed through May 2014. Inclusion criteria required FMT as the primary therapeutic agent. Clinical remission (CR) and/or mucosal healing were defined as primary outcomes. Studies were excluded if they did not report clinical outcomes or included patients with infections.<br><br>RESULTS: Eighteen studies (9 cohort studies, 8 case studies and 1 randomized controlled trial) were included. 122 patients were described (79 ulcerative colitis (UC); 39 Crohn's disease (CD); 4 IBD unclassified). Overall, 45% (54/119) of patients achieved CR during follow-up. Among the cohort studies, the pooled proportion of patients that achieved CR was 36.2% (95% CI 17.4%-60.4%), with a moderate risk of heterogeneity (Cochran's Q, P=0.011; I(2)=37%). Subgroup analyses demonstrated a pooled estimate of clinical remission of 22% (95% CI 10.4%-40.8%) for UC (P=0.37; I(2)=0%) and 60.5% (95% CI 28.4%-85.6%) for CD (P=0.05; I(2)=37%). Six studies performed microbiota analysis.<br><br>CONCLUSIONS: This analysis suggests that FMT is a safe, but variably efficacious treatment for IBD. More randomized controlled trials are needed and should investigate frequency of FMT administration, donor selection and standardization of microbiome analysis.}, }
@article {pmid25222378, year = {2014}, author = {Viswanathan, VK}, title = {The trendy microbes.}, journal = {Gut microbes}, volume = {5}, number = {4}, pages = {439-440}, doi = {10.4161/gmic.36381}, pmid = {25222378}, issn = {1949-0984}, mesh = {Biotechnology/methods/trends ; Drug Industry/methods/trends ; *Health ; Humans ; Microbiology/*trends ; Microbiota/*physiology ; }, abstract = {After dominating the earth in numbers and biomass for a good 3.5 billion years, microbes are now finally in the public consciousness. The vigorous surge in the study of microbes promises to yield novel approaches to treating diseases and maintaining health. In the middle of the deluge of scientific publications and lay articles, we pause to reflect on this trend.}, }
@article {pmid25221934, year = {2015}, author = {Mogul, D and Zhou, M and Intihar, P and Schwarz, K and Frick, K}, title = {Cost-effective analysis of screening for biliary atresia with the stool color card.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {60}, number = {1}, pages = {91-98}, doi = {10.1097/MPG.0000000000000569}, pmid = {25221934}, issn = {1536-4801}, mesh = {Biliary Atresia/*diagnosis/economics/mortality/surgery ; Cohort Studies ; Color ; Early Diagnosis ; False Positive Reactions ; Feasibility Studies ; Feces/*chemistry ; Health Care Costs ; Humans ; Infant, Newborn ; Liver Transplantation/adverse effects/economics ; Markov Chains ; Neonatal Screening/economics/*methods ; Prognosis ; Quality-Adjusted Life Years ; Sensitivity and Specificity ; United States ; }, abstract = {BACKGROUND: Biliary atresia (BA) is the leading cause of pediatric end-stage liver disease and liver transplantation in the United States. Early diagnosis leads to improved outcomes, but diagnosis is often delayed, leading to increased rates of transplantation and mortality.<br><br>METHODS: A Markov model was developed to simulate the natural history and transplant-related outcomes of patients with BA in a US cohort studied for 20 years. Data regarding proportions of individuals in different health states, including transplant and death, were obtained from published literature. Costs were derived from the literature and the Johns Hopkins database of charges using the cost-to-charge ratio. Strategy A represented the status quo and assumed no screening. Strategy B used nationwide screening with the stool color card developed by the Taiwan Health Bureau. The cost associated with both strategies was compared with the number of life-years gained, deaths, and the number of transplants for a 20-year interval. A dominant strategy was one that was associated with lower cost alongside improved outcomes, including increases in life-years gained, reductions in number of deaths, and reductions in number of transplants. One-way and probabilistic sensitivity analyses were performed.<br><br>RESULTS: In strategy A, the 20-year cost was $142,479,725 with 3702 life-years, 74 deaths and 158 liver transplants. For strategy B, the cost was $133,893,563 with 3731.7 life-years, 71 deaths and 147 liver transplants. There was a >97% probability that screening with the stool color card would be cost saving and associated with an increase in life-years gained. Among all parameters, only stool color card specificity was associated with the potential for screening to no longer be cost saving.<br><br>CONCLUSIONS: Compared with no screening, screening with the stool color card is a dominant strategy associated with lower costs and better outcomes. These findings suggest that screening with the stool color card could be an important, economically feasible strategy for improving outcomes in BA in the United States.}, }
@article {pmid25220232, year = {2014}, author = {Megerlin, F and Fouassier, E}, title = {[Faecal microbiota transplantation in France: what applicable law?].}, journal = {Annales pharmaceutiques francaises}, volume = {72}, number = {5}, pages = {363-374}, doi = {10.1016/j.pharma.2014.04.003}, pmid = {25220232}, issn = {0003-4509}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; France ; Gastrointestinal Microbiome ; Humans ; *Legislation, Medical ; }, abstract = {The transplantation of gut microbiota addresses a critical gap in the treatment of recurrent severe Clostridium difficile infection, and clinical trials are ongoing throughout the world for other potential broader clinical indications. As the fecal flora inoculum has currently no legal status under European law, we consider it provisionally a sui generis biological drug rather than a human tissue transplantation, with major implications in terms of legal liability in France. The inoculum obeys a derogation to the pharmaceutical preparation rules, is processed under microbiological control, and therefore should carry a special obligation for informed consent from recipients. Failing industrializable solutions to date, this practice for the modulation of human microbiome suggests that the current legal definition of the biologic drug as well as the rules for donation and use of human-originated substances should be complemented. A new category of therapeutic products could be considered in European law, unless a rapid technological progress (the French Agency ASNM classified FMT as a drug in March 2014).}, }
@article {pmid25220228, year = {2014}, author = {Bourlioux, P and Megerlin, F and Corthier, G and Gobert, JG and Butel, MJ}, title = {[Why could gut microbiota become a medication?].}, journal = {Annales pharmaceutiques francaises}, volume = {72}, number = {5}, pages = {325-329}, doi = {10.1016/j.pharma.2014.03.005}, pmid = {25220228}, issn = {0003-4509}, mesh = {*Fecal Microbiota Transplantation ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; Intestines/microbiology ; }, abstract = {The gut microbiota (or gut flora) is a set of bacteria living in symbiosis with the host. Strictly associated with the intestinal tract and interacting with it, the gut microbiota is not a tissue nor an organ, but a supra-organism. A disruption of dialogue between bacteria and human cells is a risk factor or a possible cause of various diseases. The restoration of this dialogue, thanks to the transfer of the gut microbiota of a healthy individual to a patient whose balance of gut flora has been broken, is a new therapeutic approach. If its exact effect still eludes scientific understanding, its clinical benefit is well established for an indication, and is recently being tested for many others. The proven contribution of gut microbiota in the human physiological balance calls for intensifying research throughout the world about the state of knowledge and technologies, as well as on the legal and ethical dimension of fecal microbiota transfer. This didactic paper updates the questions in relation with this therapeutic act.}, }
@article {pmid25213347, year = {2015}, author = {Uchiyama, R and Chassaing, B and Zhang, B and Gewirtz, AT}, title = {MyD88-mediated TLR signaling protects against acute rotavirus infection while inflammasome cytokines direct Ab response.}, journal = {Innate immunity}, volume = {21}, number = {4}, pages = {416-428}, pmid = {25213347}, issn = {1753-4267}, support = {R01 DK083890/DK/NIDDK NIH HHS/United States ; R21 AI107943/AI/NIAID NIH HHS/United States ; DK083890/DK/NIDDK NIH HHS/United States ; AI107943/AI/NIAID NIH HHS/United States ; }, mesh = {Acute Disease ; Animals ; Antibody Formation/genetics ; Cells, Cultured ; Cytokines/metabolism ; Disease Models, Animal ; Humans ; Immunity, Innate/genetics ; Inflammasomes/*metabolism ; Interleukin-18/metabolism ; Interleukin-1beta/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88/genetics/*metabolism ; Rotavirus/*immunology ; Rotavirus Infections/*immunology ; Signal Transduction/genetics ; Toll-Like Receptors/metabolism ; Transplantation Chimera ; Viral Load/genetics ; }, abstract = {Rotavirus (RV) infects small intestinal epithelial cells, inducing severe diarrhea in children, resulting in over 500,000 deaths annually. Relatively little is known about how innate immunity contains acute infection and drives adaptive immune responses that afford complete clearance of RV and protection against future infection. Hence, we examined the consequence of the absence of MyD88, known to be central to innate immunity, in a mouse model of RV infection. The absence of MyD88, but not combined blockade of IL-1β and IL-18 signaling, resulted in greater infectivity, as reflected by levels of RV in feces, intestinal lysates and viremia. Such increased RV levels correlated with an increase in incidence and duration of diarrhea. Loss of MyD88 also impaired humoral immunity to RV. Specifically, MyD88 knockout generated less RV-specific IgA and exhibited profoundly reduced RV-specific IgG2c/IgG1 ratios suggesting that MyD88 signaling drives RV-induced Th1 responses. A study of MyD88 bone marrow chimeras indicated that MyD88-dependent control of acute RV infection was mediated by both hemopoietic and non-hemopoietic cells, while generation of RV-specific humoral immunity was driven by MyD88 signaling in hemopoietic cells, which reflected the loss of IL-1β and IL-18 expression by these cells. Thus, TLR signaling and inflammasome cytokines drive innate and adaptive immunity to RV.}, }
@article {pmid25195178, year = {2014}, author = {Collier, MG and Khudyakov, YE and Selvage, D and Adams-Cameron, M and Epson, E and Cronquist, A and Jervis, RH and Lamba, K and Kimura, AC and Sowadsky, R and Hassan, R and Park, SY and Garza, E and Elliott, AJ and Rotstein, DS and Beal, J and Kuntz, T and Lance, SE and Dreisch, R and Wise, ME and Nelson, NP and Suryaprasad, A and Drobeniuc, J and Holmberg, SD and Xu, F and , }, title = {Outbreak of hepatitis A in the USA associated with frozen pomegranate arils imported from Turkey: an epidemiological case study.}, journal = {The Lancet. Infectious diseases}, volume = {14}, number = {10}, pages = {976-981}, doi = {10.1016/S1473-3099(14)70883-7}, pmid = {25195178}, issn = {1474-4457}, mesh = {Adult ; Disease Notification ; *Disease Outbreaks ; Epidemiologic Studies ; Feces/virology ; Female ; *Food Contamination ; Fruit/virology ; Genotype ; Hepatitis A/*epidemiology/prevention &amp; control/therapy ; Hepatitis A Virus, Human/genetics/immunology/*isolation &amp; purification ; Humans ; Immunoglobulins/administration &amp; dosage ; Lythraceae/*virology ; Male ; Middle Aged ; Phylogeny ; Product Recalls and Withdrawals ; Sequence Analysis, DNA ; Turkey ; United States/epidemiology ; Viral Vaccines/*administration &amp; dosage ; }, abstract = {BACKGROUND: In May, 2013, an outbreak of symptomatic hepatitis A virus infections occurred in the USA. Federal, state, and local public health officials investigated the cause of the outbreak and instituted actions to control its spread. We investigated the source of the outbreak and assessed the public health measures used.<br><br>METHODS: We interviewed patients, obtained their shopping information, and did genetic analysis of hepatitis A virus recovered from patients' serum and stool samples. We tested products for the virus and traced supply chains.<br><br>FINDINGS: Of 165 patients identified from ten states, 69 (42%) were admitted to hospital, two developed fulminant hepatitis, and one needed a liver transplant; none died. Illness onset occurred from March 31 to Aug 12, 2013. The median age of patients was 47 years (IQR 35-58) and 91 (55%) were women. 153 patients (93%) reported consuming product B from retailer A. 40 patients (24%) had product B in their freezers, and 113 (68%) bought it according to data from retailer A. Hepatitis A virus genotype IB, uncommon in the Americas, was recovered from specimens from 117 people with hepatitis A virus illness. Pomegranate arils that were imported from Turkey--where genotype IB is common--were identified in product B. No hepatitis A virus was detected in product B.<br><br>INTERPRETATION: Imported frozen pomegranate arils were identified as the vehicle early in the investigation by combining epidemiology--with data from several sources--genetic analysis of patient samples, and product tracing. Product B was removed from store shelves, the public were warned not to eat product B, product recalls took place, and postexposure prophylaxis with both hepatitis A virus vaccine and immunoglobulin was provided. Our findings show that modern public health actions can help rapidly detect and control hepatitis A virus illness caused by imported food. Our findings show that postexposure prophylaxis can successfully prevent hepatitis A illness when a specific product is identified. Imported food products combined with waning immunity in some adult populations might make this type of intervention necessary in the future.<br><br>FUNDING: US Centers for Disease Control and Prevention, US Food and Drug Administration, and US state and local public health departments.}, }
@article {pmid25193538, year = {2015}, author = {Mullish, BH and Marchesi, JR and Thursz, MR and Williams, HR}, title = {Microbiome manipulation with faecal microbiome transplantation as a therapeutic strategy in Clostridium difficile infection.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {108}, number = {5}, pages = {355-359}, pmid = {25193538}, issn = {1460-2393}, mesh = {Clostridioides difficile/*pathogenicity ; Clostridium Infections/*therapy ; Donor Selection ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; *Microbiota ; }, abstract = {Faecal microbiome transplantation (FMT) has generated huge recent interest as it presents a potential solution to a significant clinical problem--the increasing incidence of Clostridium difficile infection (CDI). In the short term, however, there remain many practical questions regarding its use, including the optimal selection of donors, material preparation and the mechanics of delivery. In the longer term, enhanced understanding of the mechanisms of action of FMT may potentiate novel therapies, such as targeted manipulation of the microbiome in CDI and beyond.}, }
@article {pmid25179208, year = {2014}, author = {Rizek, C and Fu, L and Dos Santos, LC and Leite, G and Ramos, J and Rossi, F and Guimaraes, T and Levin, AS and Costa, SF}, title = {Characterization of carbapenem-resistant Pseudomonas aeruginosa clinical isolates, carrying multiple genes coding for this antibiotic resistance.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {13}, number = {}, pages = {43}, pmid = {25179208}, issn = {1476-0711}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/*genetics ; Carbapenems/*pharmacology ; Colistin/pharmacology ; DNA, Bacterial/genetics ; Electrophoresis, Gel, Pulsed-Field ; *Genes, Bacterial ; Genotype ; Hospitals ; Humans ; Imipenem/pharmacology ; Meropenem ; Microbial Sensitivity Tests ; Molecular Typing ; Polymerase Chain Reaction ; Pseudomonas Infections/microbiology ; Pseudomonas aeruginosa/classification/*drug effects/*enzymology/isolation &amp; purification ; Thienamycins/pharmacology ; *beta-Lactam Resistance ; beta-Lactamases/*genetics ; }, abstract = {BACKGROUND: Carbapenemase genes are one of the most frequent mechanisms reported in carbapenem-resistant P. aeruginosa; however, description of P. aeruginosa co-harbouring two or more carbapenemases is unusual.<br><br>METHODS: In this study we evaluated the presence of carbapenemase genes and the clonality of P. aeruginosa isolates obtained from a hospital over a 12-year period. A total of 127 isolates of carbapenem-resistant P. aeruginosa recovered from 109 patients feces (four samples), rectal swab (three samples), nasal swab (one sample) and anal abscess (one sample), were evaluated. Minimum inhibitory concentrations of the following antibiotics imipenem, meropenem and polymyxin E were determined by broth microdilution. The molecular profile of isolates was evaluated by pulsed field gel electrophoresis (PFGE). PCR for the following carbapenemase genes blaIMP;blaSPM;blaVIM;blaSIM;blaNDM;blaKPC;blaGES and nucleotide sequencing to confirm the enzyme gene types were performed and compared with the database available on the Internet (BLAST-http://www.ncbi.nlm.nhi.gov/blast/).<br><br>RESULTS: All isolates were carbapenem-resistant, their MIC50 and MIC90 were respectively 64 &#x3bc;g/mL and 256 &#x3bc;g/mL to imipenem and 32 &#x3bc;g/mL and 256 &#x3bc;g/mL to meropenem, all isolates except one (MIC = 8 mg/L) were susceptible to polymyxin E. The most frequent carbapenemase genes identified were blaSPM identified in 41 isolates (32%), followed by 10 with blakpc and 5 with blaVIM (3.9%). All belonged to the class SPM-1 and VIM-2. In 2011, one isolate harbouring three carbapenemase genes (SPM-1, VIM-2 and KPC-2) that belonged to a new clone was identified in a hematopoietic stem cell transplanted patient. Then, 19 carbapenem-resistant P. aeruginosa were identified in an outbreak that occurred in the bone marrow transplant unit, all positive for SPM-1 gene, and 9 (47.3%) harbored both SPM-1 and KPC.<br><br>CONCLUSION: Our findings showed that PCR for KPC gene should be performed to evaluate carbapenem resistance in P. aeruginosa and that this agent can harbor more than one carbapenemase gene. Attention should be focused on the possible rapid spread of KPC in P. aeruginosa isolates and for the fact that P. aeruginosa may become a reservoir of this transmissible resistance mechanism.}, }
@article {pmid25171964, year = {2014}, author = {Lemes, LG and Corrêa, TS and Fiaccadori, FS and Cardoso, Dd and Arantes, Ade M and Souza, KM and Souza, M}, title = {Prospective study on Norovirus infection among allogeneic stem cell transplant recipients: prolonged viral excretion and viral RNA in the blood.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {61}, number = {3}, pages = {329-333}, doi = {10.1016/j.jcv.2014.08.004}, pmid = {25171964}, issn = {1873-5967}, mesh = {Adult ; Caliciviridae Infections/*epidemiology/virology ; Cluster Analysis ; Female ; Genotype ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction ; Norovirus/*isolation &amp; purification ; Phylogeny ; Prospective Studies ; RNA, Viral/*blood/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sapovirus/isolation &amp; purification ; Sequence Analysis, DNA ; Stem Cell Transplantation ; Stem Cells ; *Transplant Recipients ; Transplantation, Homologous ; *Virus Shedding ; Young Adult ; }, abstract = {BACKGROUND: Human caliciviruses (Norovirus and Sapovirus) are important acute gastroenteritis agents. The Norovirus (NoV) disease is usually self-limited; however, prolonged viral excretion and complications have been reported, mainly in immunosuppressed individuals.<br><br>OBJECTIVES: In this prospective study, we have monitored allogeneic stem cell transplant (ASCT) patients for human calicivirus infection.<br><br>STUDY DESIGN: Ten ASCT patients were monitored for NoV and sapoviruses (SaV) infection, for a period of five months to a maximum of one year. Prolonged NoV excretion and long term viral RNA in the blood were assessed by multiplex RT-PCR targeting region C of the viral capsid. Secretor status of the patients was determined by enzyme immunoassay using Ulex Europaeus agglutinin. Partial genomic sequencing and phylogenetic analysis were performed to characterize the viral genotypes.<br><br>RESULTS: NoV was detected in six out of ten patients (60%). Prolonged viral excretion in feces (mean of 61.6 days) and long term presence of NoV RNA in the sera (mean of 33.6 days) of the patients were observed. SaV was not detected in any of the samples. All patients had diarrhea, vomiting and fever during NoV positivity. All NoV-positive samples were characterized as GI.3 NoV. Three Nov-infected patients presented with acute intestinal graft versus host disease.<br><br>CONCLUSIONS: This study brings important information on NoV course of infection in ASCT patients. It also provides evidence for long term viral RNA in the blood highlighting the importance of the inclusion of NoV screening in the routine testing performed before transplantation and during follow-up of these patients.}, }
@article {pmid25168749, year = {2015}, author = {Cui, B and Feng, Q and Wang, H and Wang, M and Peng, Z and Li, P and Huang, G and Liu, Z and Wu, P and Fan, Z and Ji, G and Wang, X and Wu, K and Fan, D and Zhang, F}, title = {Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: safety, feasibility, and efficacy trial results.}, journal = {Journal of gastroenterology and hepatology}, volume = {30}, number = {1}, pages = {51-58}, doi = {10.1111/jgh.12727}, pmid = {25168749}, issn = {1440-1746}, mesh = {Adolescent ; Adult ; Aged ; Biological Therapy/*methods ; Child ; Colon/*microbiology ; Crohn Disease/*microbiology/*therapy ; Feasibility Studies ; Feces/*microbiology ; Female ; Humans ; Male ; Metagenome ; *Microbiota/genetics ; Middle Aged ; Pilot Projects ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND AND AIM: The gut microbiota plays a pivotal role in the intestinal diseases. Fecal microbiota transplantation (FMT) might be a rescue therapy for refractory inflammatory bowel disease. This study aimed to evaluate the safety, feasibility, and efficacy of FMT through mid-gut for refractory Crohn's disease (CD).<br><br>METHODS: We established standardized laboratory protocol and clinical work flow for FMT. Only refractory CD patients with Harvey-Bradshaw Index (HBI) score&#x2009;&#x2265;&#x2009;7 were enrolled for this study. All included patients were treated with single FMT through mid-gut and assessed during follow-up.<br><br>RESULTS: Metagenomics analysis showed a high concordance between feces sample and purified fecal microbiota from same donors. Standardized fecal microbiota preparation and clinical flow significantly simplified the practical aspects of FMT. Totally, 30 patients were qualified for the present analysis. The rate of clinical improvement and remission based on clinical activity at the first month was 86.7% (26/30) and 76.7% (23/30), respectively, which was higher than other assessment points within 15-month follow-up. Patients' body weight increased after FMT, and the lipid profile improved as well. FMT also showed a fast and continuous significant effect in relieving the sustaining abdominal pain associated with sustaining CD.<br><br>CONCLUSION: This is a pilot study with the largest sample of patients with refractory CD who underwent single FMT. The results demonstrated that FMT through mid-gut might be a safe, feasible, and efficient rescue therapy for refractory CD.}, }
@article {pmid25168489, year = {2014}, author = {Peer, X and An, G}, title = {Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection.}, journal = {Journal of pharmacokinetics and pharmacodynamics}, volume = {41}, number = {5}, pages = {493-507}, pmid = {25168489}, issn = {1573-8744}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; P50 GM053789/GM/NIGMS NIH HHS/United States ; P30DK42086/DK/NIDDK NIH HHS/United States ; P50GM53789/GM/NIGMS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Bile Acids and Salts/*metabolism ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/drug therapy/*metabolism/microbiology/*therapy ; Feces/*microbiology ; Humans ; *Models, Biological ; *Transplantation ; }, abstract = {Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the C. difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, fecal microbial transplant. The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of personalized medicine.}, }
@article {pmid25167835, year = {2014}, author = {Yeh, YT and Tsai, HL and Chen, CY and Wang, JB and Chin, TW and Wei, CF and Liu, CS}, title = {Surgical outcomes of total colonic aganglionosis in children: a 26-year experience in a single institute.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {77}, number = {10}, pages = {519-523}, doi = {10.1016/j.jcma.2014.05.012}, pmid = {25167835}, issn = {1728-7731}, mesh = {Female ; Hirschsprung Disease/*surgery ; Humans ; Infant ; Male ; Retrospective Studies ; }, abstract = {BACKGROUND: There is a lack of consensus regarding the treatment of total colonic aganglionosis (TCA) with respect to perioperative morbidity, mortality, complications, and functional outcomes. The aim of this study was to review the results of surgical TCA treatment over a 26-year period and characterize the outcomes.<br><br>METHODS: We retrospectively reviewed the clinical characteristics, surgical courses, and outcomes of TCA patients who underwent definitive pull-through operations from 1986 to 2012. Follow-up data were collected by chart reviews and telephone interviews using a standardized questionnaire.<br><br>RESULTS: We identified nine infants with TCA (8.6%) from among 105 infants with Hirschsprung's disease treated during the 26-year period. Neither sex predominated (male/female ratio = 4:5). All infants underwent laparotomies and simultaneous enterostomies. All patients eventually underwent modified Duhamel pull-through procedures at a mean age of 179 days (range, 47-352 days). Two infants died of complications after surgery including heart failure and sepsis. The remaining infants recovered smoothly with antilaxative medications, and all but one was weaned off these medications. Although the surviving patients did not catch up on growth, they and their families were satisfied with the surgical results.<br><br>CONCLUSION: Infants with TCA had satisfactory outcomes after the modified Duhamel pull-through operation. Based on our experience, we suggest that the pull-through operation could be performed earlier, even when there are loose stools from the enterostomy.}, }
@article {pmid25162366, year = {2015}, author = {Suskind, DL and Singh, N and Nielson, H and Wahbeh, G}, title = {Fecal microbial transplant via nasogastric tube for active pediatric ulcerative colitis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {60}, number = {1}, pages = {27-29}, doi = {10.1097/MPG.0000000000000544}, pmid = {25162366}, issn = {1536-4801}, mesh = {Adolescent ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Colitis, Ulcerative/drug therapy/microbiology/physiopathology/*therapy ; Combined Modality Therapy/adverse effects ; Donor Selection ; Feces/microbiology ; Follow-Up Studies ; Hospitals, Pediatric ; Humans ; Immunosuppressive Agents/therapeutic use ; Intubation, Gastrointestinal ; Male ; *Microbiota ; Outpatient Clinics, Hospital ; Probiotics/therapeutic use ; Severity of Illness Index ; *Therapies, Investigational/adverse effects ; Washington ; }, abstract = {BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory disease of the large intestine, is characterized by a dysregulated immune reaction. UC is associated with fecal dysbiosis. Human and animal studies support the fact that the gastrointestinal microbiome may trigger the intestinal immune response, resulting in UC. Fecal microbial transplantation (FMT), by changing the gastrointestinal microbiome of patients with UC, may be a therapeutic option.<br><br>METHODS: Four patients with moderate symptoms defined by the Pediatric Ulcerative Colitis Activity Index were enrolled in a prospective, open-label study of FMT via nasogastric tube in pediatric UC (US Food and Drug Administration IND 14942). After the donor and patient evaluation, patients received FMT with follow-up evaluations at 2, 6, and 12 weeks after transplantation. Study subjects were maintained on their pretransplant medications. The Pediatric Ulcerative Colitis Activity Index score, C-reactive protein, and stool calprotectin were completed during each study visit.<br><br>RESULTS: Four patients with UC were enrolled (all boys). Ages ranged from 13 to 16 years. Patients tolerated FMT without adverse effects. None of the patients clinically improved with FMT, nor were there any significant changes in stool calprotectin or laboratory values, including C-reactive protein, albumin, and hematocrit. Three individuals received additional standard medical therapies before the end of the study.<br><br>CONCLUSIONS: This study, although showing that single-dose FMT via nasogastric tube is well tolerated in active pediatric UC, did not show any clinical or laboratory benefit.}, }
@article {pmid25162365, year = {2015}, author = {Kronman, MP and Nielson, HJ and Adler, AL and Giefer, MJ and Wahbeh, G and Singh, N and Zerr, DM and Suskind, DL}, title = {Fecal microbiota transplantation via nasogastric tube for recurrent clostridium difficile infection in pediatric patients.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {60}, number = {1}, pages = {23-26}, doi = {10.1097/MPG.0000000000000545}, pmid = {25162365}, issn = {1536-4801}, mesh = {Child ; Child, Preschool ; Clostridioides difficile/growth &amp; development/immunology/*isolation &amp; purification ; Comorbidity ; Donor Selection ; Enterocolitis, Pseudomembranous/epidemiology/immunology/microbiology/*therapy ; Feces/microbiology ; Female ; Follow-Up Studies ; Hospitals, Pediatric ; Humans ; Immunocompromised Host ; Intubation, Gastrointestinal ; Male ; *Microbiota ; Recurrence ; Retrospective Studies ; *Therapies, Investigational/adverse effects ; Washington/epidemiology ; }, abstract = {Fecal microbiota transplantation (FMT) is a safe and effective therapy for adults with recurrent Clostridium difficile colitis, but data regarding FMT in children are limited and focus on colonoscopic administration of FMT. We present 10 consecutive children who received FMT via nasogastric tube for treatment of recurrent C difficile infection. Median age was 5.4 years, and 30% were receiving simultaneous immunosuppression. Median follow-up was 44 days, and 90% of patients resolved their C difficile infection; one patient relapsed 2 months later after receiving antibiotics. FMT via nasogastric tube appears safe, well tolerated, and effective in treating pediatric recurrent C difficile colitis.}, }
@article {pmid25156678, year = {2014}, author = {Le Monnier, A and Zahar, JR and Barbut, F}, title = {Update on Clostridium difficile infections.}, journal = {Medecine et maladies infectieuses}, volume = {44}, number = {8}, pages = {354-365}, doi = {10.1016/j.medmal.2014.04.002}, pmid = {25156678}, issn = {1769-6690}, mesh = {*Clostridioides difficile ; *Clostridium Infections/diagnosis/drug therapy/etiology/microbiology/physiopathology ; Cost of Illness ; Humans ; Risk Factors ; }, abstract = {Clostridium difficile infections (CDI) occur primarily in hospitalized patients with risk factors such as concomitant or recent use of antibiotics. CDI related additional costs are important for the global population and health-care facilities. CDI epidemiology has changed since 2003: they became more frequent boosted by large outbreaks, more severe, more resistant to antibiotic treatment, and spread to new groups of population without any risk factor. This is partly due to the emergence and worldwide dissemination of new and more virulent C. difficile strains such as the epidemic clone 027/NAP1/BI. The host immune response plays a central role in the pathogenesis of CDI and could also be involved in the occurrence of recurrent or severe forms. New guidelines including new molecular tests (NAAT) have recently clarified and simplified the diagnostic strategies for the microbiological diagnosis of CDI. The CDI incidence was proven to be related to the level of clinical suspicion and the frequency of microbiological screening for C. difficile. The current recommendations for the treatment of CDI mention oral metronidazole as the first line treatment for mild to moderate diarrhea. Oral vancomycin use should be restricted to severe cases. In the absence of consensus, the treatment of multiple recurrences remains a major concern. New and more targeted antibiotics and innovative therapeutic strategies (fecal transplantation, monoclonal antibodies, and vaccination) have emerged as new therapies for CDI.}, }
@article {pmid25156371, year = {2014}, author = {Agrawal, G and Borody, TJ and Chamberlin, W}, title = {'Global warming' to Mycobacterium avium subspecies paratuberculosis.}, journal = {Future microbiology}, volume = {9}, number = {7}, pages = {829-832}, doi = {10.2217/fmb.14.52}, pmid = {25156371}, issn = {1746-0921}, mesh = {Anti-Bacterial Agents/therapeutic use ; Crohn Disease/epidemiology/immunology/*microbiology ; Global Health ; Humans ; Macrophages/immunology ; Mycobacterium avium subsp. paratuberculosis/drug effects/genetics/isolation &amp; purification/*physiology ; Phagocytosis ; }, }
@article {pmid25141333, year = {2014}, author = {Karakan, T}, title = {Fecal microbiota transplant in immunocompromised patients: Encouraging results in a vulnarable population.}, journal = {The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology}, volume = {25}, number = {3}, pages = {346}, doi = {10.5152/tjg.2014.0013}, pmid = {25141333}, issn = {2148-5607}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/*microbiology/*therapy ; Feces/*microbiology ; Female ; Humans ; *Immunocompromised Host ; Male ; *Microbiota ; }, }
@article {pmid25136848, year = {2014}, author = {Li, Q and Wang, C and Tang, C and He, Q and Li, J}, title = {Lymphocyte depletion after alemtuzumab induction disrupts intestinal fungal microbiota in cynomolgus monkeys.}, journal = {Transplantation}, volume = {98}, number = {9}, pages = {951-959}, doi = {10.1097/TP.0000000000000373}, pmid = {25136848}, issn = {1534-6080}, mesh = {Alemtuzumab ; Animals ; Antibodies, Monoclonal, Humanized/*pharmacology ; Antigens, CD/metabolism ; Antigens, Neoplasm/metabolism ; Aspergillus/drug effects ; CD52 Antigen ; Candida albicans/drug effects ; DNA, Ribosomal/analysis ; Erythrocytes/immunology ; Feces/microbiology ; Glycoproteins/metabolism ; Immunosuppressive Agents/pharmacology ; Intestinal Mucosa/immunology/microbiology ; Intestines/*microbiology ; Lymphocyte Depletion/*methods ; Lymphocytes/*cytology ; Macaca fascicularis ; Male ; Microbiota/*drug effects ; Saccharomyces cerevisiae/drug effects ; Time Factors ; }, abstract = {BACKGROUND: The interactions of specific fungal phylotypes with immune cells have been recently documented; however, little is known whether gut fungal microbiota is influenced by aberrant immune response in immunosuppressive state. This study aimed to define the biologic impact of lymphocyte depletion on gut fungal microbiota and their relationship.<br><br>METHODS: Fifteen male cynomolgus monkeys with CD52 antigen negative on erythrocytes were administered intravenously with a single dose (3.0 mg kg body weight) of alemtuzumab. Depletion and repopulation of circulating and mucosal lymphocytes were determined. The dynamic variations of intestinal fungal microbiota were characterized using 18S ribosomal DNA-based molecular techniques.<br><br>RESULTS: The fungal microbiota in colonal mucosa was perturbed during lymphocyte depletion, characterized by increased diversity and colonization of Candida albicans, Aspergillus clavatus, and Saccharomyces cerevisiae. The diversity of the fecal fungal population decreased markedly after mucosal lymphocyte depletion, and specific fungal phylotypes, especially Candida albicans, Saccharomyces cerevisiae, and Botryotinia fuckeliana, were expanded (P<0.05). After reconstitution of mucosal lymphocytes, the composition and diversity of the gut fungal microbiota were both recovered. A close association of the community diversity and Candida albicans colonization with T lymphocyte subsets was also identified.<br><br>CONCLUSION: Our findings demonstrate that mucosal lymphocyte depletion leads to the dysbiosis of gut fungal microbiota, suggesting its role in maintaining host-fungus homeostasis. The pathophysiologic consequences of this altered fungal colonization might provide novel clues to uncover the underlying mechanism of enteric fungal infection in immunosuppressive therapies.}, }
@article {pmid25135141, year = {2014}, author = {Beneš, J and Husa, P and Nyč, O and Polívková, S}, title = {[Diagnosis and therapy of Clostridium difficile infection: Czech national guidelines].}, journal = {Klinicka mikrobiologie a infekcni lekarstvi}, volume = {20}, number = {2}, pages = {56-66}, pmid = {25135141}, issn = {1211-264X}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology ; Czech Republic/epidemiology ; Diarrhea/microbiology ; Enterocolitis, Pseudomembranous/*diagnosis/epidemiology/metabolism ; Feces/microbiology ; Health Policy ; Humans ; Practice Guidelines as Topic ; }, abstract = {Clostridium difficile infection (CDI) is a disease of varying severity. Its manifestations range from mild diarrhea to life-threatening paralytic ileus, painful distension of the large bowel, and sepsis. Another possible manifestation of the disease is recurring colitis that can exhaust the patient. For establishing the diagnosis, the patient's stool should be examined with two or three different microbiological methods (testing for clostridial toxins A and B; testing for clostridial glutamate dehydrogenase, anaerobic culture with specific media, or PCR detection of genes for production of clostridial toxins). An alternative way of assessing the etiology is colonoscopic examination; the disease is confirmed if characteristic patchy pseudomembranes are present in the bowel mucosa. Optimal treatment depends on severity of the disease and on the risk of recurrence. Metronidazole, vancomycin and fidaxomicin are used as basic drugs. Fecal transplantation is effective in recurrent disease. In the hospital setting, patients suffering from CDI should be isolated for the entire duration of diarrhea. Surveillance rules also should be applied, together with early treatment of symptomatic patients and prevention of the spread of the infection. Higher incidence of CDI in a ward implies that the local antibiotic prescription habits should be revised.}, }
@article {pmid25119613, year = {2014}, author = {Hohmann, EL and Ananthakrishnan, AN and Deshpande, V}, title = {Case Records of the Massachusetts General Hospital. Case 25-2014. A 37-year-old man with ulcerative colitis and bloody diarrhea.}, journal = {The New England journal of medicine}, volume = {371}, number = {7}, pages = {668-675}, doi = {10.1056/NEJMcpc1400842}, pmid = {25119613}, issn = {1533-4406}, mesh = {Adult ; Colitis, Ulcerative/complications/*pathology ; Colon/*pathology ; Cytomegalovirus Infections/complications/diagnosis/*pathology ; Diagnosis, Differential ; Diarrhea/etiology ; Gastrointestinal Hemorrhage/etiology ; Humans ; Male ; Spasm/etiology ; }, abstract = {A 37-year-old man with ulcerative colitis was admitted to the hospital because of abdominal cramping, diarrhea, hematochezia, fever to a peak temperature of 38.8 °C, and drenching night sweats. Several weeks earlier, he had performed home fecal transplantation.}, }
@article {pmid25117129, year = {2014}, author = {Holme, &#xd8; and Løberg, M and Kalager, M and Bretthauer, M and Hernán, MA and Aas, E and Eide, TJ and Skovlund, E and Schneede, J and Tveit, KM and Hoff, G}, title = {Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial.}, journal = {JAMA}, volume = {312}, number = {6}, pages = {606-615}, pmid = {25117129}, issn = {1538-3598}, support = {P01 CA134294/CA/NCI NIH HHS/United States ; R35 CA197449/CA/NCI NIH HHS/United States ; }, mesh = {Colorectal Neoplasms/diagnosis/*epidemiology/mortality/prevention &amp; control ; *Early Detection of Cancer ; Female ; Humans ; Incidence ; Intention to Treat Analysis ; Male ; Middle Aged ; Norway/epidemiology ; Occult Blood ; *Sigmoidoscopy/instrumentation ; }, abstract = {IMPORTANCE: Colorectal cancer is a major health burden. Screening is recommended in many countries.<br><br>OBJECTIVE: To estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population-based trial.<br><br>Randomized clinical trial of 100,210 individuals aged 50 to 64 years, identified from the population of Oslo city and Telemark County, Norway. Screening was performed in 1999-2000 (55-64-year age group) and in 2001 (50-54-year age group), with follow-up ending December 31, 2011. Of those selected, 1415 were excluded due to prior colorectal cancer, emigration, or death, and 3 could not be traced in the population registry.<br><br>INTERVENTIONS: Participants randomized to the screening group were invited to undergo screening. Within the screening group, participants were randomized 1:1 to receive once-only flexible sigmoidoscopy or combination of once-only flexible sigmoidoscopy and fecal occult blood testing (FOBT). Participants with positive screening test results (cancer, adenoma, polyp &#x2265;10 mm, or positive FOBT) were offered colonoscopy. The control group received no intervention.<br><br>MAIN OUTCOMES AND MEASURES: Colorectal cancer incidence and mortality.<br><br>RESULTS: A total of 98,792 participants were included in the intention-to-screen analyses, of whom 78,220 comprised the control group and 20,572 comprised the screening group (10,283 randomized to receive a flexible sigmoidoscopy and 10,289 to receive flexible sigmoidoscopy and FOBT). Adherence with screening was 63%. After a median of 10.9 years, 71 participants died of colorectal cancer in the screening group vs 330 in the control group (31.4 vs 43.1 deaths per 100,000 person-years; absolute rate difference, 11.7 [95% CI, 3.0-20.4]; hazard ratio [HR], 0.73 [95% CI, 0.56-0.94]). Colorectal cancer was diagnosed in 253 participants in the screening group vs 1086 in the control group (112.6 vs 141.0 cases per 100,000 person-years; absolute rate difference, 28.4 [95% CI, 12.1-44.7]; HR, 0.80 [95% CI, 0.70-0.92]). Colorectal cancer incidence was reduced in both the 50- to 54-year age group (HR, 0.68; 95% CI, 0.49-0.94) and the 55- to 64-year age group (HR, 0.83; 95% CI, 0.71-0.96). There was no difference between the flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening groups.<br><br>CONCLUSIONS AND RELEVANCE: In Norway, once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence and mortality on a population level compared with no screening. Screening was effective both in the 50- to 54-year and the 55- to 64-year age groups.<br><br>TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00119912.}, }
@article {pmid25106113, year = {2014}, author = {Khoruts, A and Weingarden, AR}, title = {Emergence of fecal microbiota transplantation as an approach to repair disrupted microbial gut ecology.}, journal = {Immunology letters}, volume = {162}, number = {2 Pt A}, pages = {77-81}, pmid = {25106113}, issn = {1879-0542}, support = {UL1 TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*physiology ; Drug Resistance ; Dysbiosis/*therapy ; Enterocolitis, Pseudomembranous/*therapy ; Feces/microbiology ; Homeostasis ; Humans ; Intestines/microbiology/*physiology ; Microbiota/*physiology ; *Transplantation ; }, abstract = {In the recent years fecal microbiota transplantation (FMT) has emerged as an effective therapeutic option for patients with refractory Clostridium difficile infection that is not responding to antibiotic therapy. It results in implantation of donor microbiota into recipients and restoration of normal distal gut microbial community structure. We anticipate that this form of therapy represents merely the first entry into a new class of therapeutics. There is great interest in application of FMT or defined microbial consortia to treatment of many diseases associated with dysbiosis. However, many challenges remain in development as our understanding of microbial ecology within the human body and microbiota-host interactions remain limited. Future advances in this field will be critically depending on detailed mechanistic understanding.}, }
@article {pmid25105126, year = {2014}, author = {Daca, A and Jarzembowski, T and Witkowski, JM and Bryl, E and Rutkowski, B and Dębska-Ślizień, A}, title = {Prophages in enterococcal isolates from renal transplant recipients: renal failure etiologies promote selection of strains.}, journal = {BioMed research international}, volume = {2014}, number = {}, pages = {514689}, pmid = {25105126}, issn = {2314-6141}, mesh = {Bacterial Proteins/biosynthesis ; *Enterococcus faecalis/genetics/isolation &amp; purification/metabolism/pathogenicity/virology ; Female ; Gene Expression Regulation, Bacterial/physiology ; *Gram-Positive Bacterial Infections/genetics/metabolism/virology ; Humans ; Kidney Failure, Chronic/etiology/*microbiology ; *Kidney Transplantation ; Male ; *Prophages/genetics/metabolism ; *Transplant Recipients ; }, abstract = {Infections caused by commensal bacteria may be fatal for the patients under immunosuppressive therapy. This results also from difficulty in identification of high risk strains. Enterococcal infections are increasingly frequent but despite many studies on virulence traits, the difference between commensal and pathogenic strains remains unclear. Prophages are newly described as important elements in competition between strains during colonization, as well as pathogenicity of the strains. Here we evaluate a difference in presence of pp4, pp1, and pp7 prophages and ASA (aggregation substance) gene expression in enterococcal isolates from renal transplant recipients (RTx) with different etiology of the end-stage renal failure. Prophages sequence was screened by PCR in strains of Enterococcus faecalis isolated from urine and feces of 19 RTx hospitalized at Medical University of Gdansk and 18 healthy volunteers. FLOW-FISH method with use of linear locked nucleic acid (LNA) probe was used to assess the ASA gene expression. Additionally, ability of biofilm formation was screened by crystal violet staining method. Presence of prophages was more frequent in fecal isolates from immunocompromised patients than in isolates from healthy volunteers. Additionally, both composition of prophages and ASA gene expression were related to the etiology of renal disease.}, }
@article {pmid25103109, year = {2014}, author = {Alcock, J and Maley, CC and Aktipis, CA}, title = {Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {36}, number = {10}, pages = {940-949}, pmid = {25103109}, issn = {1521-1878}, support = {F32 CA132450/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA149566/CA/NCI NIH HHS/United States ; P01 CA91955/CA/NCI NIH HHS/United States ; R01CA170595/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Feeding Behavior ; Gastrointestinal Tract/*microbiology ; Humans ; *Microbiota ; Models, Biological ; Obesity/etiology ; }, abstract = {Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness. Microbes may do this through two potential strategies: (i) generating cravings for foods that they specialize on or foods that suppress their competitors, or (ii) inducing dysphoria until we eat foods that enhance their fitness. We review several potential mechanisms for microbial control over eating behavior including microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review the evidence for alternative explanations for cravings and unhealthy eating behavior. Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating.}, }
@article {pmid25095866, year = {2014}, author = {Fløe, A and Leutscher, P}, title = {[Recurrent Clostridium difficile infection treated with faecal microbiota transplantation].}, journal = {Ugeskrift for laeger}, volume = {176}, number = {4}, pages = {}, pmid = {25095866}, issn = {1603-6824}, mesh = {Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; Clostridium Infections/drug therapy/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Humans ; Male ; Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {Treatment of severe Clostridium difficile infection (CDI) poses a clinical challenge. Emerging evidence supports the use of faecal microbiota transplantation (FMT). An 81-year-old man was admitted with a third recurrent episode of CDI within two months. Because of clinical deterioration with development of pancolitis in spite of two weeks of metronidazole and vanco-mycin treatment, FMT was performed using a duodenal tube. The patient recovered completely without further relapse during follow-up. FMT was shown to be an efficient adjuvant treatment of complicated CDI.}, }
@article {pmid25095865, year = {2014}, author = {Carstensen, JW and Hansen, AK}, title = {[Faecal transplantation as a treatment for Clostridium difficile infection, ulcerative colitis and the metabolic syndrome].}, journal = {Ugeskrift for laeger}, volume = {176}, number = {4}, pages = {}, pmid = {25095865}, issn = {1603-6824}, mesh = {Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Colitis, Ulcerative/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Humans ; Metabolic Syndrome/microbiology/*therapy ; }, abstract = {Faecal transplantation as a therapeutic tool is increasingly reported in the scientific literature. Faecal transplantation is currently becoming a treatment for nosocomial, refractory infections with C. difficile. Furthermore, faecal transplantation has been suggested as a treatment for ulcerative colitis as well as for the metabolic syndrome. In the accumulated literature faecal transplantations appear to be safe, effective and superior to current treatments. Faecal transplantation remains a sparsely investigated treatment, however, especially for other diagnoses than C. difficile infection.}, }
@article {pmid25079328, year = {2014}, author = {Qin, N and Yang, F and Li, A and Prifti, E and Chen, Y and Shao, L and Guo, J and Le Chatelier, E and Yao, J and Wu, L and Zhou, J and Ni, S and Liu, L and Pons, N and Batto, JM and Kennedy, SP and Leonard, P and Yuan, C and Ding, W and Chen, Y and Hu, X and Zheng, B and Qian, G and Xu, W and Ehrlich, SD and Zheng, S and Li, L}, title = {Alterations of the human gut microbiome in liver cirrhosis.}, journal = {Nature}, volume = {513}, number = {7516}, pages = {59-64}, pmid = {25079328}, issn = {1476-4687}, mesh = {Case-Control Studies ; Chronic Disease ; Diabetes Mellitus, Type 2/microbiology ; Feces/microbiology ; Gastrointestinal Tract/*microbiology ; Genetic Markers/genetics ; Health ; Humans ; Inflammatory Bowel Diseases/microbiology ; Liver Cirrhosis/*diagnosis/*microbiology ; *Metagenomics ; Microbiota/*genetics/*physiology ; Mouth/microbiology ; Phylogeny ; Reproducibility of Results ; }, abstract = {Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.}, }
@article {pmid25066028, year = {2014}, author = {Ganswindt, SB and Myburgh, JG and Cameron, EZ and Ganswindt, A}, title = {Non-invasive assessment of adrenocortical function in captive Nile crocodiles (Crocodylus niloticus).}, journal = {Comparative biochemistry and physiology. Part A, Molecular &amp; integrative physiology}, volume = {177}, number = {}, pages = {11-17}, doi = {10.1016/j.cbpa.2014.07.013}, pmid = {25066028}, issn = {1531-4332}, mesh = {Adrenal Cortex/*metabolism/*transplantation ; Adrenocorticotropic Hormone/*metabolism ; Alligators and Crocodiles/blood/*metabolism/*physiology ; Animals ; Corticosterone/blood ; Environment ; Feces/chemistry ; Female ; Glucocorticoids/metabolism ; Male ; Stress, Physiological/physiology ; }, abstract = {The occurrence of stress-inducing factors in captive crocodilians is a concern, since chronic stress can negatively affect animal health and reproduction, and hence production. Monitoring stress in wild crocodiles could also be beneficial for assessing the state of health in populations which are potentially threatened by environmental pollution. In both cases, a non-invasive approach to assess adrenocortical function as a measure of stress would be preferable, as animals are not disturbed during sample collection, and therefore sampling is feedback-free. So far, however, such a non-invasive method has not been established for any crocodilian species. As an initial step, we therefore examined the suitability of two enzyme-immunoassays, detecting faecal glucocorticoid metabolites (FGMs) with a 11β,21-diol-20-one and 5β-3α-ol-11-one structure, respectively, for monitoring stress-related physiological responses in captive Nile crocodiles (Crocodylus niloticus). An adrenocorticotropic hormone (ACTH) challenge was performed on 10 sub-adult crocodiles, resulting in an overall increase in serum corticosterone levels of 272% above the pre-injection levels 5h post-injection. Saline-treated control animals (n=8) showed an overall increase of 156% in serum corticosterone levels 5h post-administration. Faecal samples pre- and post-injection could be obtained from three of the six individually housed crocodiles, resulting in FGM concentrations 136-380% above pre-injection levels, always detected in the first sample collected post-treatment (7-15 days post-injection). FGM concentrations seem comparatively stable at ambient temperatures for up to 72 h post-defaecation. In conclusion, non-invasive hormone monitoring can be used for assessing adrenocortical function in captive Nile crocodiles based on FGM analysis.}, }
@article {pmid25065404, year = {2014}, author = {Chandra, A and Malhotra, HS and M, N and Gupta, V and Singh, SK and Kumar, N and Lalla, RS and Chandra, A and Garg, RK}, title = {Neuromodulation of perineally transposed antropylorus with pudendal nerve anastomosis following total anorectal reconstruction in humans.}, journal = {Neurogastroenterology and motility}, volume = {26}, number = {9}, pages = {1342-1348}, doi = {10.1111/nmo.12398}, pmid = {25065404}, issn = {1365-2982}, mesh = {Adolescent ; Adult ; Anal Canal/innervation/*physiopathology/*surgery ; Anastomosis, Surgical ; Electric Stimulation ; Electromyography ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Middle Aged ; Pudendal Nerve/*physiopathology ; Pylorus/innervation/*physiopathology/*transplantation ; Plastic Surgery Procedures ; Young Adult ; }, abstract = {BACKGROUND: We have reported perineal antropyloric segment transposition with its pudendal innervation as a replacement for anal sphincter. Our aim herein was to neuromodulate this segment by electrical stimulation.<br><br>METHODS: Eight patients with a permanent colostomy underwent perineal antropyloric segment transposition followed by neural anastomosis of its anterior vagus branch to pudendal nerve branch in the perineum. Perineal antropyloric graft was assessed for its functional integrity and electrophysiological effects. Nerve stimulation was done by surface stimulation technique, using a customized stimulation protocol for smooth muscle. Antral pressures were recorded on voluntary attempts and on nerve stimulation with simultaneous concentric needle electromyography of the perineal antropylorus.<br><br>KEY RESULTS: The antral segment showed slow spontaneous contractions (2-3/min) on digital examination, endoscopy, and electrophysiology. Stimulated antropyloric electromyography showed a latency of 2-5 s with a differential rise in amplitude (mean range 58.57-998.75 &#x3bc;V) according to the frequency of stimulation (range 10-150 Hz). An average latency of 10 s in relation to rise in the antral pressure was observed on pudendal nerve stimulation. Triggering of the intrinsic rhythm was observed in patients where it was initially absent. Voluntary attempts at contraction also showed a rise in perineally transposed antral pressure.<br><br>CONCLUSIONS &amp; INFERENCES: Spontaneous rhythm, its generation after electrical stimulation, and response to voluntary contraction demonstrates the viability and functional reinnervation of the perineally transposed antropyloric segment. Rise in pressure on electrical stimulation shows evidence for its neuromodulation.}, }
@article {pmid25064318, year = {2014}, author = {Dickinson, B and Surawicz, CM}, title = {Infectious diarrhea: an overview.}, journal = {Current gastroenterology reports}, volume = {16}, number = {8}, pages = {399}, pmid = {25064318}, issn = {1534-312X}, mesh = {Diarrhea/epidemiology/*microbiology/*therapy ; Enterocolitis, Pseudomembranous/complications/therapy ; Fluid Therapy/methods ; Humans ; Irritable Bowel Syndrome/microbiology ; Probiotics/therapeutic use ; Zinc/therapeutic use ; }, abstract = {Diarrheal disease, which is most often caused by infectious pathogens, is a significant cause of morbidity and mortality worldwide, especially in children. This is particularly true in developing countries. Recent outbreaks of infectious diarrhea in developed countries, including the USA, are often attributed to food handling and distribution practices and highlight the need for continued vigilance in this area. Another common cause of infectious diarrhea, Clostridium difficile infection (CDI), has historically been associated with the use of antibiotics and exposure to a health-care setting but is now increasingly common in the community in persons who lack the typical risk factors. Recent scientific advances have also led to new and proposed new therapies for infectious diarrhea, including fecal microbiota transplant (FMT) for recurrent C. difficile infection (RCDI), probiotics for prevention of antibiotic-associated diarrhea (AAD) and CDI, and the use of zinc supplementation in the treatment of acute diarrhea in children. Other therapies that have been in use for decades, such as the oral rehydration solution (ORS), continue to be the targets of scientific advancement in an effort to improve delivery and efficacy. Finally, post-infectious irritable bowel syndrome (PI-IBS) is an increasingly recognized occurrence. Attempts to understand the mechanism behind this phenomenon are underway and may provide insight into potential treatment options.}, }
@article {pmid25064227, year = {2014}, author = {Ramachandran, P and Shanmugam, NP and Sinani, SA and Shanmugam, V and Srinivas, S and Sathiyasekaran, M and Tamilvanan, V and Rela, M}, title = {Outcome of partial internal biliary diversion for intractable pruritus in children with cholestatic liver disease.}, journal = {Pediatric surgery international}, volume = {30}, number = {10}, pages = {1045-1049}, pmid = {25064227}, issn = {1437-9813}, mesh = {Bile Ducts/*surgery ; Biliary Tract Surgical Procedures/*methods ; Child ; Child, Preschool ; Cholestasis/*complications/*surgery ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Pruritus/*etiology/*surgery ; Treatment Outcome ; }, abstract = {PURPOSE: Children with cholestatic disorders have undergone liver transplantation for intractable pruritus unresponsive to medical therapy even in the absence of liver failure. Biliary diversion procedures interrupt the entero-hepatic circulation of bile acids allowing them to be excreted in the feces thereby lowering the total bile acid pool. We evaluated the outcome of partial internal biliary diversion (PIBD) in children with intractable pruritus from inherited cholestatic disorders.<br><br>METHODS: The records of children who underwent PIBD over a 4-year period were reviewed for etiology of liver disease, demographic data, preoperative and postoperative biochemical profile and improvement of pruritus. Standard statistical methods were used for analysis.<br><br>RESULTS: Of the 12 children, 10 had progressive familial intrahepatic cholestasis (PFIC) and 2 had Alagille syndrome (AS). PIBD was done using an isolated jejunal loop as a conduit from gall bladder to mid ascending colon. Median period of follow up was 30&#xa0;months. Pruritus resolved in nine children with significant reduction of serum bile acids (P&#xa0;<&#xa0;0.02).<br><br>CONCLUSION: To our knowledge, this is the largest reported series of children with PIBD. PIBD is a safe, well-tolerated and effective alternative to liver transplant in children with PFIC and AS who have intractable pruritus in the absence of synthetic liver failure.}, }
@article {pmid25052150, year = {2015}, author = {Zainah, H and Hassan, M and Shiekh-Sroujieh, L and Hassan, S and Alangaden, G and Ramesh, M}, title = {Intestinal microbiota transplantation, a simple and effective treatment for severe and refractory Clostridium difficile infection.}, journal = {Digestive diseases and sciences}, volume = {60}, number = {1}, pages = {181-185}, pmid = {25052150}, issn = {1573-2568}, mesh = {Aged ; Aged, 80 and over ; Biological Therapy/*methods ; *Clostridioides difficile ; Colonoscopy ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Intestines/*microbiology ; Intubation, Gastrointestinal ; Male ; Microbiota ; Recurrence ; Retrospective Studies ; }, abstract = {BACKGROUND: Restoring normal fecal flora through intestinal microbiota transplantation (IMT) was successful in curing recurrent Clostridium difficile infection (CDI). However, only a few cases have been reported of IMT being utilized for the treatment of severe or fulminant CDI.<br><br>AIM: Is IMT a simple and effective treatment for severe and recurrent CDI?<br><br>METHODS: In this retrospective study, we report 14 patients with severe CDI refractory to conventional medical therapy, who underwent IMT. Fresh donor stool specimen was manually homogenized with warm tap water, filtered through gauze and then instilled through nasogastric tube (NGT). The primary outcome was clinical cure, defined as less than 3 loose bowel movements a day on day 7 after IMT and no need for further CDI therapy. The secondary outcomes were recurrence of CDI within 100 days of IMT and 30-day mortality after IMT. Descriptive statistics were done.<br><br>RESULTS: Fourteen patients with severe and refractory CDI received IMT. Mean age was 73.4 &#xb1; 11.9 years (range 52-92). IMT was given via NGT in 13 of the 14 patients. Eleven patients (79 %) achieved cure after IMT. No recurrence was seen in the patients who responded to IMT and were alive within the 100 day follow-up period. IMT was well tolerated. The 30-day all-cause mortality was 29 %, all 4 patients died as a result of their underlying cancer. No patients died as a result of CDI or IMT.<br><br>CONCLUSIONS: IMT performed at the bedside via NGT is effective and safe for the treatment of severe and refractory CDI, and prevents recurrence.}, }
@article {pmid25046331, year = {2014}, author = {Walia, R and Kunde, S and Mahajan, L}, title = {Fecal microbiota transplantation in the treatment of refractory Clostridium difficile infection in children: an update.}, journal = {Current opinion in pediatrics}, volume = {26}, number = {5}, pages = {573-578}, doi = {10.1097/MOP.0000000000000127}, pmid = {25046331}, issn = {1531-698X}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Biological Therapy/*methods ; Child ; Child, Preschool ; Clostridioides difficile/*drug effects ; Clostridium Infections/immunology/microbiology/*therapy ; Enterocolitis, Pseudomembranous/immunology/microbiology/*therapy ; Feces/*microbiology ; Humans ; Immunocompromised Host ; Infant ; Intubation, Gastrointestinal ; Metagenome ; Microbiota/*immunology ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: The use of transplanted fecal material for the treatment of diarrheal illness dates back to the fourth-century China. While fecal microbiota transplant has gained increasing popularity over the past 50 years for the treatment of refractory Clostridium difficile infections (RCDIs) in adults, it has only been recently utilized in children. The purpose of this article is to review the use of fecal microbiota transplant (FMT) in the treatment of pediatric RCDIs.<br><br>RECENT FINDINGS: Minimal pediatric data, including few case reports and series, document the successful use of FMT for treatment of RCDI in the past 2 years. Patients in these reports included otherwise healthy children, those with inflammatory bowel disease as well as significantly immunocompromised children. Donor fecal infusion via nasogastric tube, gastroscope or colonoscope in children aged 16 months and older demonstrated a high rate of symptom resolution and organism eradication. No complications to date have been reported in children who have undergone FMT.<br><br>SUMMARY: FMT is emerging as a well-tolerated and effective treatment for RCDI in not only adults but also children.}, }
@article {pmid25044451, year = {2014}, author = {Dietert, RR}, title = {The microbiome in early life: self-completion and microbiota protection as health priorities.}, journal = {Birth defects research. Part B, Developmental and reproductive toxicology}, volume = {101}, number = {4}, pages = {333-340}, doi = {10.1002/bdrb.21116}, pmid = {25044451}, issn = {1542-9741}, mesh = {Female ; Humans ; Microbial Consortia ; *Microbiota ; Parturition ; Prebiotics ; Pregnancy ; Probiotics/*therapeutic use ; }, abstract = {This minireview considers the benefits of refocusing attention away from treating the patient as a mammalian human to managing the complete patient: a majority microbial superorganism. Under the "completed self" model for formation of the human-microbial superorganism, the single, most pivotal sign in distinguishing a life course of health versus that filled with disease is self-completion (i.e., seeding of the minority mammalian human by the majority microbial portion of the symbiont). From a disease prevention perspective, microbial seeding at birth and subsequent nurturing of the microbiota are significant steps to reduce the risk of both noncommunicable diseases (e.g., type 1 diabetes) and certain infectious diseases. Management of the microbiome during pregnancy, birth, and shortly thereafter appears to be the most significant critical window for healthy superorganism formation. However, the bolus for microbiota seeding at birth and the nurturing process are subject to environmental influences and disruption, such as exposure to toxic chemicals and drugs, infections, and other physical and psychological stressors. Additionally, childhood and adult corrective measures, such as fecal transplantation and administration of prebiotics and probiotics, while potentially useful, may have limitations that are yet to be fully defined. This minireview considers (1) basic features of management of the microbiome to facilitate self-completion, (2) protection of the microbiota from environmental hazards, and (3) the benefits of using a superorganism focus for health management beginning with pregnancy and extending throughout childhood and adult life.}, }
@article {pmid25041704, year = {2014}, author = {Kronman, MP and Zerr, DM and Qin, X and Englund, J and Cornell, C and Sanders, JE and Myers, J and Rayar, J and Berry, JE and Adler, AL and Weissman, SJ}, title = {Intestinal decontamination of multidrug-resistant Klebsiella pneumoniae after recurrent infections in an immunocompromised host.}, journal = {Diagnostic microbiology and infectious disease}, volume = {80}, number = {1}, pages = {87-89}, pmid = {25041704}, issn = {1879-0070}, support = {R01 AI083413/AI/NIAID NIH HHS/United States ; R01AI083413/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacteremia/drug therapy/microbiology ; Drug Resistance, Multiple, Bacterial ; Feces/microbiology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunocompromised Host ; Klebsiella Infections/drug therapy/*microbiology ; Klebsiella pneumoniae/classification/*drug effects/genetics ; Male ; Recurrence ; Skin Diseases, Bacterial/drug therapy/microbiology ; Transplant Recipients ; Young Adult ; }, abstract = {Multidrug-resistant (MDR) Enterobacteriaceae infections are associated with increased morbidity. We describe a 20-year-old hematopoietic cell transplantation recipient with recurrent MDR Klebsiella pneumoniae infection, prolonged intestinal colonization, and subsequent intestinal decontamination. Further study should evaluate stool surveillance, molecular typing, and fecal microbiota transplantation for patients with intestinal MDR Enterobacteriaceae carriage.}, }
@article {pmid25041100, year = {2014}, author = {Bonot, S and Ogorzaly, L and El Moualij, B and Zorzi, W and Cauchie, HM}, title = {Detection of small amounts of human adenoviruses in stools: comparison of a new immuno real-time PCR assay with classical tools.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {20}, number = {12}, pages = {O1010-6}, pmid = {25041100}, issn = {1469-0691}, mesh = {Adenoviridae Infections/*diagnosis ; Adenoviruses, Human/*isolation &amp; purification ; Child, Preschool ; Diagnostic Tests, Routine/*methods ; Feces/*virology ; Humans ; Immunoassay/methods ; Real-Time Polymerase Chain Reaction/*methods ; Sensitivity and Specificity ; }, abstract = {The detection of low virus concentrations in biological matrices, especially stool samples, is facing significant limitations as far as common diagnostic methods (enzyme-linked-immunosorbent assay (ELISA) or quantitative real-time PCR (qPCR)) are considered. Here the development of a new immuno real-time PCR (iPCR) is described and its performance in the detection of human adenoviruses (HAdVs) in spiked stools is compared with those of ELISA and qPCR assays. For the iPCR, detection of the sandwich formed by the complexation of capture antibody-antigen-detection antibody was performed by qPCR thanks to the substitution of peroxydase by a chimeric DNA. This modification increased the detection sensitivity 200-fold compared to ELISA. The direct qPCR results revealed that only 0.3-9.5% of the spiked HAdV were detectable, resulting from important losses of DNA occurring at the extraction step. This step was not necessary in the iPCR workflow, avoiding this drawback. The losses of viral particles occurred at the elution step from the stool only. The recovery rate of the iPCR was thus better and ranged between 21 and 54%. As a result, iPCR enabled the detection of lower virus concentrations in stool samples compared to those detected by ELISA and qPCR. The iPCR could be considered as a 'hyper sensitive ELISA' for early detection of HAdV infections, especially in the case of immunocompromised patients after haematopoietic stem cell transplant.}, }
@article {pmid25036411, year = {2015}, author = {Dai, C and Jiang, M and Sun, MJ}, title = {Fecal microbiota transplantation for treatment of Clostridium difficile infection.}, journal = {Journal of clinical gastroenterology}, volume = {49}, number = {2}, pages = {171-172}, doi = {10.1097/MCG.0000000000000189}, pmid = {25036411}, issn = {1539-2031}, mesh = {Clostridium Infections/*therapy ; Diarrhea/*therapy ; Feces/*microbiology ; Humans ; }, }
@article {pmid25034424, year = {2014}, author = {Högenauer, C and Kump, PK and Krause, R}, title = {Tempered enthusiasm for fecal transplantation?.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {59}, number = {9}, pages = {1348-1349}, doi = {10.1093/cid/ciu567}, pmid = {25034424}, issn = {1537-6591}, mesh = {Biological Therapy/*methods ; Drugs, Investigational/*therapeutic use ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; *Investigational New Drug Application ; }, }
@article {pmid25023578, year = {2014}, author = {Walia, R and Garg, S and Song, Y and Girotra, M and Cuffari, C and Fricke, WF and Dutta, SK}, title = {Efficacy of fecal microbiota transplantation in 2 children with recurrent Clostridium difficile infection and its impact on their growth and gut microbiome.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {59}, number = {5}, pages = {565-570}, doi = {10.1097/MPG.0000000000000495}, pmid = {25023578}, issn = {1536-4801}, mesh = {Bacteroides/growth &amp; development ; *Biological Therapy ; Child, Preschool ; *Clostridioides difficile/growth &amp; development ; Clostridium Infections/microbiology/*therapy ; Feces/*microbiology ; *Growth ; Humans ; Infant ; Intestines/*microbiology ; Male ; *Microbiota ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is recognized as an alternative therapeutic modality for recurrent Clostridium difficile infection (RCDI); however, data on its efficacy in children are lacking, including its effect on their growth and fecal microbiota. We report on 2 young children (<3 years old) who failed available therapeutics for RCDI, but responded remarkably well to FMT. Besides resolution of clinical features of C difficile infection (CDI), FMT administration led to marked improvement in their growth, along with increased microbiota diversity, especially proportion of Bacteroides. Our 2 cases illustrate the efficacy of FMT in children with RCDI and its positive effect on their growth and gut microbiota.}, }
@article {pmid25014180, year = {2014}, author = {Khan, MA and Sofi, AA and Ahmad, U and Alaradi, O and Khan, AR and Hammad, T and Pratt, J and Sodeman, T and Sodeman, W and Kamal, S and Nawras, A}, title = {Efficacy and safety of, and patient satisfaction with, colonoscopic-administered fecal microbiota transplantation in relapsing and refractory community- and hospital-acquired Clostridium difficile infection.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {28}, number = {8}, pages = {434-438}, pmid = {25014180}, issn = {2291-2797}, mesh = {Aged ; Aged, 80 and over ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/*therapy ; Colonoscopy/*methods ; Cross Infection/microbiology/therapy ; Diarrhea/microbiology/*therapy ; Feces/*microbiology ; Female ; Follow-Up Studies ; Humans ; Male ; Microbiota ; Middle Aged ; Patient Satisfaction ; Recurrence ; Retreatment ; Retrospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVE: To report the efficacy and safety of, and patient satisfaction with, colonoscopic fecal microbiota transplantation (FMT) for community- and hospital-acquired Clostridium difficile infection (CDI).<br><br>METHODS: A retrospective medical records review of patients who underwent FMT between July 1, 2012 and August 31, 2013 was conducted. A total of 22 FMTs were performed on 20 patients via colonoscopy. The patients were divided into 'community-acquired' and 'hospital-acquired' CDI. Telephone surveys were conducted to determine procedure outcome and patient satisfaction. Primary cure rate was defined as resolution of diarrhea without recurrence within three months of FMT, whereas secondary cure rate described patients who experienced resolution of diarrhea and return of normal bowel function after a second course of FMT.<br><br>RESULTS: Nine patients met the criteria for community-acquired CDI whereas 11 were categorized as hospital-acquired CDI. A female predominance in the community-acquired group (88.89% [eight of nine]) was found (P=0.048). The primary cure rate was 100% (nine of nine) and 81.8% (nine of 11 patients) in community- and hospital-acquired CDI groups, respectively (P=0.189). Two patients in the hospital-acquired group had to undergo a repeat FMT for persistent symptomatic infection; the secondary cure rate was 100%. During the six-month follow-up, all patients were extremely satisfied with the procedure and no complications or adverse events were reported.<br><br>CONCLUSION: FMT was a highly successful and very acceptable treatment modality for treating both community- and hospital-acquired CDI.}, }
@article {pmid25009198, year = {2014}, author = {Schreiber, RA and Masucci, L and Kaczorowski, J and Collet, JP and Lutley, P and Espinosa, V and Bryan, S}, title = {Home-based screening for biliary atresia using infant stool colour cards: a large-scale prospective cohort study and cost-effectiveness analysis.}, journal = {Journal of medical screening}, volume = {21}, number = {3}, pages = {126-132}, doi = {10.1177/0969141314542115}, pmid = {25009198}, issn = {1475-5793}, support = {HERU1/CSO_/Chief Scientist Office/United Kingdom ; 210874/CAPMC/CIHR/Canada ; }, mesh = {Biliary Atresia/*diagnosis ; Color ; Cost-Benefit Analysis ; Diagnostic Techniques, Digestive System/economics ; Feces ; Humans ; Infant, Newborn ; Prospective Studies ; Self Care ; }, abstract = {OBJECTIVE: Biliary atresia (BA), a leading cause of paediatric liver failure and liver transplantation, manifests by three weeks of life as jaundice with acholic stools. Poor outcomes due to delayed diagnosis remain a problem worldwide. We evaluated and assessed the cost-effectiveness of methods of introducing a BA Infant Stool Colour Card (ISCC) screening programme in Canada.<br><br>SETTING AND METHODS: A prospective study at BC Women's Hospital recruited consecutive healthy newborns through six incrementally more intensive screening approaches. Under the baseline "passive" strategy, families received ISCCs at maternity, with instructions to monitor infant stool colour daily and return the ISCC by mail at age 30 days. Additional strategies were: ISCC mailed to family physician; reminder letters or telephone calls to families or physicians. Random telephone surveys of ISCC non-returners assessed total card utilization. Primary outcome was ISCC utilization rate expressed as a composite outcome of the ISCC return rate and non-returned ISCC use. Markov modelling was used to predict incremental costs and life years gained from screening (passive and reminder), compared with no screening, over a 10-year time horizon.<br><br>RESULTS: 6,187 families were enrolled. Card utilization rates in the passive screening strategy were estimated at 60-94%. For a Canadian population, the increase in cost for passive screening, compared with no screening, is $213,584 and the gain in life years is 9.7 ($22,000 per life-year gained).<br><br>CONCLUSIONS: A BA ISCC screening programme targeting families of newborns is feasible in Canada. Passive distribution of ISCC at maternity is potentially effective and highly cost-effective.}, }
@article {pmid25004996, year = {2014}, author = {Xie, Y and Chen, H and Zhu, B and Qin, N and Chen, Y and Li, Z and Deng, M and Jiang, H and Xu, X and Yang, J and Ruan, B and Li, L}, title = {Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.}, journal = {Microbial ecology}, volume = {68}, number = {4}, pages = {871-880}, pmid = {25004996}, issn = {1432-184X}, mesh = {Animal Feed/analysis ; Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Bacteria/*drug effects/genetics/growth &amp; development ; DNA, Bacterial/genetics/metabolism ; Diet ; Dietary Supplements/analysis ; *Graft Rejection ; Intestines/*microbiology ; Liver/*physiopathology ; *Liver Transplantation ; Male ; Microbiota/genetics/physiology ; Molecular Sequence Data ; Phylogeny ; Probiotics/administration &amp; dosage ; RNA, Ribosomal, 16S/genetics/metabolism ; Rats ; Sequence Analysis, DNA ; }, abstract = {The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-β were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-β and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.}, }
@article {pmid25003516, year = {2014}, author = {Clavel, T and Desmarchelier, C and Haller, D and Gérard, P and Rohn, S and Lepage, P and Daniel, H}, title = {Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance.}, journal = {Gut microbes}, volume = {5}, number = {4}, pages = {544-551}, doi = {10.4161/gmic.29331}, pmid = {25003516}, issn = {1949-0984}, mesh = {Animals ; Bacteria/*classification/*metabolism ; *Biota ; Cholesterol/metabolism ; Gastrointestinal Tract/*microbiology ; Metabolic Diseases/*etiology ; Mice, Obese ; }, abstract = {The trillions of bacterial cells that colonize the mammalian digestive tract influence both host physiology and the fate of dietary compounds. Gnotobionts and fecal transplantation have been instrumental in revealing the causal role of intestinal bacteria in energy homeostasis and metabolic dysfunctions such as type-2 diabetes. However, the exact contribution of gut bacterial metabolism to host energy balance is still unclear and knowledge about underlying molecular mechanisms is scant. We have previously characterized cecal bacterial community functions and host responses in diet-induced obese mice using omics approaches. Based on these studies, we here discuss issues on the relevance of mouse models, give evidence that the metabolism of cholesterol-derived compounds by gut bacteria is of particular importance in the context of metabolic disorders and that dominant species of the family Coriobacteriaceae are good models to study these functions.}, }
@article {pmid24997882, year = {2014}, author = {Megerlin, F and Fouassier, E and Lopert, R and Bourlioux, P}, title = {Faecal microbiota transplantation: a sui generis biological drug, not a tissue.}, journal = {Annales pharmaceutiques francaises}, volume = {72}, number = {4}, pages = {217-220}, doi = {10.1016/j.pharma.2014.04.008}, pmid = {24997882}, issn = {0003-4509}, mesh = {Animals ; Clostridium Infections/*therapy ; Feces/*microbiology ; Humans ; Tissue Transplantation/*legislation &amp; jurisprudence ; }, abstract = {Responding to Smith et al. (Nature, 2014), this paper argues that for medical use, faecal microbiota transplantation (FMT) should be considered a sui generis biological drug, rather than a tissue. Smith and colleagues' thesis is based on possible undesirable economic consequences of this designation--not on its scientific and conceptual basis. The faecal transplant (including gut microbiota, metabolites, mucus, human cells, viruses, fungi, etc.) is not a tissue; it is of topographic--not cellular--human origin. We consider the donor a bioreactor, producing the faecal substrate of therapeutic interest. The debate is of singular importance as the FDA considers FMT a drug and released a new guidance for public consultation in February 2014, whereas to date the European Medicines Agency has not promulgated its position. The UK's National Institute for Heath and Care Excellence does not consider FMT to involve the transplantation of body tissue, and in March 2014 the French regulatory agency ANSM expressly declared it to be a drug. As FM is a complex and highly variable admixture, its components cannot be completely characterized, and to date, compositional quality cannot be assessed. We consider FMT to be a sui generis biologic drug, albeit one prepared with unconventional raw material under microbiologic control. The possibility of associating identified bacterial species with particular diseases and cultivating selected bacteria of therapeutic interest would certainly define a second generation of microbiome therapeutics, but is still speculative.}, }
@article {pmid24991448, year = {2014}, author = {Goudarzi, M and Seyedjavadi, SS and Goudarzi, H and Mehdizadeh Aghdam, E and Nazeri, S}, title = {Clostridium difficile Infection: Epidemiology, Pathogenesis, Risk Factors, and Therapeutic Options.}, journal = {Scientifica}, volume = {2014}, number = {}, pages = {916826}, pmid = {24991448}, issn = {2090-908X}, abstract = {The incidence and mortality rate of Clostridium difficile infection have increased remarkably in both hospital and community settings during the last two decades. The growth of infection may be caused by multiple factors including inappropriate antibiotic usage, poor standards of environmental cleanliness, changes in infection control practices, large outbreaks of C. difficile infection in hospitals, alteration of circulating strains of C. difficile, and spread of hypervirulent strains. Detection of high-risk populations could be helpful for prompt diagnosis and consequent treatment of patients suffering from C. difficile infection. Metronidazole and oral vancomycin are recommended antibiotics for the treatment of initial infection. Current treatments for C. difficile infection consist of supportive care, discontinuing the unnecessary antibiotic, and specific antimicrobial therapy. Moreover, novel approaches include fidaxomicin therapy, monoclonal antibodies, and fecal microbiota transplantation mediated therapy. Fecal microbiota transplantation has shown relevant efficacy to overcome C. difficile infection and reduce its recurrence.}, }
@article {pmid24989088, year = {2014}, author = {Seril, DN and Shen, B}, title = {Clostridium difficile infection in patients with ileal pouches.}, journal = {The American journal of gastroenterology}, volume = {109}, number = {7}, pages = {941-947}, doi = {10.1038/ajg.2014.22}, pmid = {24989088}, issn = {1572-0241}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; Clostridium Infections/*diagnosis/drug therapy/*microbiology ; Colonic Pouches/*microbiology ; Endoscopy ; Humans ; Postoperative Complications/*diagnosis/drug therapy/*microbiology ; Proctocolectomy, Restorative ; Risk Factors ; Sex Factors ; Vancomycin/therapeutic use ; }, abstract = {Clostridium difficile (C. difficile) infection (CDI) following total proctocolectomy and ileal pouch-anal anastomosis has been increasingly recognized over the past 5 years. CDI of the ileal pouch has been recognized in ∼10% of symptomatic patients seen at a tertiary referral center for pouch dysfunction. In contrast to colonic CDI in the general population or in patients with inflammatory bowel disease, postoperative antibiotic exposure and the use of immunosuppressive agents or proton pump inhibitors do not appear to be associated with CDI of the pouch. Male gender, recent hospitalization, and presurgery antibiotic use were shown to be risk factors for ileal pouch CDI. The ileal pouch may be susceptible to CDI owing to similarities with the colon at physiological and structural levels. Postcolectomy CDI likely represents a spectrum of disease processes, varying from asymptomatic colonization to severe symptomatic infection. CDI should be considered in any patient with an ileal pouch presenting with a change in "normal" symptom pattern or treatment-refractory disease. Sensitive and specific methods for the detection of CDI are available, and pouchoscopy is a valuable tool in the evaluation of the patient with symptomatic CDI of the pouch. At a referral center for pouch dysfunction, vancomycin is used as the first-line therapy for ileal pouch CDI. Fecal microbiota transplantation may find use in the management of severe or antibiotic refractory CDI-related pouchitis.}, }
@article {pmid24987314, year = {2014}, author = {}, title = {CRITICAL VIEWS IN GASTROENTEROLOGY &amp; HEPATOLOGY: Fecal Microbiota Transplantation: Where Is It Leading?.}, journal = {Gastroenterology &amp; hepatology}, volume = {10}, number = {5}, pages = {307-309}, pmid = {24987314}, issn = {1554-7914}, }
@article {pmid24983544, year = {2014}, author = {Schünemann, M and Oette, M}, title = {Fecal microbiota transplantation for Clostridium difficile-associated colitis in a severely immunocompromized critically ill AIDS patient: a case report.}, journal = {AIDS (London, England)}, volume = {28}, number = {5}, pages = {798-799}, doi = {10.1097/QAD.0000000000000148}, pmid = {24983544}, issn = {1473-5571}, mesh = {Acquired Immunodeficiency Syndrome/*complications ; Biological Therapy/*methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Colitis/microbiology/*therapy ; Critical Illness ; Feces/*microbiology ; Humans ; Immunocompromised Host ; Male ; Middle Aged ; Treatment Outcome ; }, }
@article {pmid24981019, year = {2014}, author = {Echenique, IA and Angarone, MP and Bolon, MK}, title = {A bridge too far.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {16}, number = {5}, pages = {866-867}, doi = {10.1111/tid.12258}, pmid = {24981019}, issn = {1399-3062}, mesh = {End Stage Liver Disease/*surgery ; Enterobacteriaceae/*isolation &amp; purification ; Enterobacteriaceae Infections/*microbiology ; Feces/*microbiology ; Female ; Humans ; *Liver Transplantation ; Male ; *Preoperative Period ; beta-Lactamases/*metabolism ; *beta-Lactams ; }, }
@article {pmid24976806, year = {2014}, author = {Aroniadis, OC and Brandt, LJ}, title = {Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease.}, journal = {Gastroenterology &amp; hepatology}, volume = {10}, number = {4}, pages = {230-237}, pmid = {24976806}, issn = {1554-7914}, support = {UL1 TR001073/TR/NCATS NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) refers to the infusion of a fecal suspension from a healthy person into the gastrointestinal (GI) tract of another person to cure a specific disease. FMT is by no means a new therapeutic modality, although it was only relatively recently that stool was shown to be a biologically active, complex mixture of living organisms with great therapeutic potential for recurrent Clostridium difficile infection and perhaps other GI and non-GI disorders. The published revelations about the human microbiome are bringing the strength of science to clinical observation and enhancing the understanding of not only disease but also how much of a person's daily function and health depends on the microorganisms living in intimate relationship with each cell in the body.}, }
@article {pmid24973448, year = {2014}, author = {Shanmugam, NK and Trebicka, E and Fu, LL and Shi, HN and Cherayil, BJ}, title = {Intestinal inflammation modulates expression of the iron-regulating hormone hepcidin depending on erythropoietic activity and the commensal microbiota.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {193}, number = {3}, pages = {1398-1407}, pmid = {24973448}, issn = {1550-6606}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; P30DK040561/DK/NIDDK NIH HHS/United States ; R01AI089700/AI/NIAID NIH HHS/United States ; R01 AI089700/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteroides fragilis/immunology ; Colitis/chemically induced/genetics/immunology ; Dextran Sulfate/administration &amp; dosage ; Disease Models, Animal ; Erythropoiesis/genetics/*immunology ; Erythropoietin/blood/*metabolism ; Female ; Hepcidins/biosynthesis/*genetics ; Homeostasis/immunology ; Inflammation Mediators/*blood ; Inflammatory Bowel Diseases/immunology/*microbiology/pathology ; Interleukin-10/deficiency/genetics ; Intestinal Mucosa/*immunology/microbiology/pathology ; Iron/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microbiota/*immunology ; STAT3 Transcription Factor/physiology ; Streptococcaceae/immunology ; }, abstract = {States of chronic inflammation such as inflammatory bowel disease are often associated with dysregulated iron metabolism and the consequent development of an anemia that is caused by maldistribution of iron. Abnormally elevated expression of the hormone hepcidin, the central regulator of systemic iron homeostasis, has been implicated in these abnormalities. However, the mechanisms that regulate hepcidin expression in conditions such as inflammatory bowel disease are not completely understood. To clarify this issue, we studied hepcidin expression in mouse models of colitis. We found that dextran sulfate sodium-induced colitis inhibited hepcidin expression in wild-type mice but upregulated it in IL-10-deficient animals. We identified two mechanisms contributing to this difference. Firstly, erythropoietic activity, as indicated by serum erythropoietin concentrations and splenic erythropoiesis, was higher in the wild-type mice, and pharmacologic inhibition of erythropoiesis prevented colitis-associated hepcidin downregulation in these animals. Secondly, the IL-10 knockout mice had higher expression of multiple inflammatory genes in the liver, including several controlled by STAT3, a key regulator of hepcidin. The results of cohousing and fecal transplantation experiments indicated that the microbiota was involved in modulating the expression of hepcidin and other STAT3-dependent hepatic genes in the context of intestinal inflammation. Our observations thus demonstrate the importance of erythropoietic activity and the microbiota in influencing hepcidin expression during colitis and provide insight into the dysregulated iron homeostasis seen in inflammatory diseases.}, }
@article {pmid24969288, year = {2014}, author = {Wine, E}, title = {Should we be treating the bugs instead of cytokines and T cells?.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {32}, number = {4}, pages = {403-409}, doi = {10.1159/000358146}, pmid = {24969288}, issn = {1421-9875}, mesh = {Animals ; Cytokines/*metabolism ; Humans ; Inflammatory Bowel Diseases/microbiology ; *Microbiota ; Models, Biological ; T-Lymphocytes/*metabolism ; Translational Research, Biomedical ; }, abstract = {BACKGROUND/AIM: It is now clear that intestinal microbes are involved in many aspects of inflammatory bowel diseases (IBD) and that understanding how microbes lead to disease could present novel opportunities for diagnosis and treatment. Microbes are linked to most disease-associated genetic polymorphisms and are critical mediators of environmental effects (through food, hygiene, and infection). This paper reviews recent findings and future implications for targeting microbes in IBD.<br><br>METHODS: A comprehensive review of the literature is presented, with specific focus on how treating microbes could alter patient care in the future.<br><br>RESULTS: Human and animal-based research supports the central role of microbes in IBD pathogenesis at multiple levels. Antibiotics, probiotics, diet, and potentially fecal transplantation are all potential treatments for IBD. Animal models of IBD only develop in the presence of microbes and co-housing mice genetically susceptible to gut inflammation with normal mice can lead to the development of bowel injury. Key papers have used microbial sequencing and metagenomics to study the role of microbes in IBD and we are now on the cusp of expanding into clinically relevant fields, such as diagnosis and therapeutics. However, many challenges still remain in understanding how microbes can be manipulated to prevent or treat disease.<br><br>CONCLUSIONS: In the future, we may be able to predict risk of disease, define biological subtypes, establish tools for prevention, and even cure IBD using microbes or their products. A broad spectrum of therapeutic tools, spanning from fecal transplantation, probiotics, prebiotics, microbial products to microbe-tailored diets, may replace current IBD treatments.}, }
@article {pmid24969143, year = {2014}, author = {Verbeke, KA and Boesmans, L and Boets, E}, title = {Modulating the microbiota in inflammatory bowel diseases: prebiotics, probiotics or faecal transplantation?.}, journal = {The Proceedings of the Nutrition Society}, volume = {73}, number = {4}, pages = {490-497}, doi = {10.1017/S0029665114000639}, pmid = {24969143}, issn = {1475-2719}, mesh = {Animals ; Clostridioides difficile/growth &amp; development/isolation &amp; purification ; Disease Models, Animal ; Escherichia coli/growth &amp; development/isolation &amp; purification ; Humans ; Inflammatory Bowel Diseases/*microbiology/*therapy ; Intestinal Mucosa/microbiology ; Intestines/microbiology ; *Microbiota ; *Prebiotics ; Probiotics/*administration &amp; dosage ; }, abstract = {Crohn's disease (CD) and ulcerative colitis (UC) are the two major phenotypes of inflammatory bowel diseases (IBD) which constitute a spectrum of chronic, debilitating diseases characterised by a relapsing inflammation of the intestinal mucosal lining. Evidence from a variety of disciplines implicates the intestinal microbiota in the pathogenesis of idiopathic IBD and their complications, including pouchitis. Many studies have reported a dysbiosis in IBD, characterised by a decrease in diversity, a decreased abundance of some dominant commensal members (such as Clostridium IV and XIVa) and an increase in detrimental bacteria (such as sulphate reducing bacteria and Escherichia coli). Therapies such as prebiotics and probiotics aim to selectively manipulate the intestinal microbiota and have been evaluated as an attractive therapeutic option with few side effects. The multispecies product VSL#3 was found effective in preventing and maintaining remission in pouchitis, whereas both VSL#3 and E. coli Nissle were effective in maintaining remission in UC. A more drastic approach to restore the composition of the microbiota and correct the underlying imbalance is a faecal microbiota transplantation (FMT). FMT has been successfully applied to treat patients with even recalcitrant Clostridium difficile infection. Particularly in UC, the majority of studies suggest that FMT may be an effective treatment option although the evidence is still limited. It is anticipated that our increasing knowledge on the composition and function of the intestinal microbiota components will allow in the future for a better selection of highly performing bacteria with specific functions required for specific benefits.}, }
@article {pmid24967561, year = {2014}, author = {Bianchi, VA and Rocchetta, I and Luquet, CM}, title = {Biomarker responses to sewage pollution in freshwater mussels (Diplodon chilensis) transplanted to a Patagonian river.}, journal = {Journal of environmental science and health. Part A, Toxic/hazardous substances &amp; environmental engineering}, volume = {49}, number = {11}, pages = {1276-1285}, doi = {10.1080/10934529.2014.910065}, pmid = {24967561}, issn = {1532-4117}, mesh = {Animals ; Argentina ; Biomarkers/analysis/metabolism ; Bivalvia/*chemistry/metabolism ; Catalase/*analysis/metabolism ; Environmental Monitoring ; Glutathione Transferase/*analysis/metabolism ; Lipid Peroxidation ; Rivers/chemistry ; Sewage/adverse effects/*analysis ; Water Pollutants, Chemical/*analysis/metabolism ; Water Pollution, Chemical/adverse effects/analysis ; }, abstract = {Field and laboratory experiments were combined to evaluate biomarker responses of Diplodon chilensis to sewage pollution. Mussels from an unpolluted area in Lacar lake (S0) were caged at a reference site (S1) and at two sites with increasing sewage pollution (S2, S3) in Pocahullo river (all in Argentina). After 1 month, gill (g) glutathione S-transferase (GST) and catalase (CAT) activities, and lipid peroxidation (TBARS) were found to be significantly elevated in S3, gGST being positively correlated with fecal bacteria (FC) concentration. Digestive gland (dg) enzyme activities were depressed and dgTBARS were increased in all transplanted mussels. After 3 mo, most variables returned to control levels in S1 mussels except for dgCAT and dgTBARS. After seven months, GST and CAT activities of S0 and S3 mussels were evaluated in the laboratory, before and after acute exposure (8 h) to high fecal bacteria concentration ([FC] in S3x 2). gGST increased in both groups, while dgGST responded only in S3 mussels. gCAT and dgCAT activities were similarly increased by acute exposure in both groups. Our results suggest that gGST and gCAT are suitable biomarkers for high FC pollution regardless of previous exposure history. In addition, we show that dgCAT is sensitive to the acute increase in FC load, both in naive and long-term exposed individuals, while dgGST becomes responsive after long-term acclimatization.}, }
@article {pmid24967088, year = {2014}, author = {Baxter, NT and Zackular, JP and Chen, GY and Schloss, PD}, title = {Structure of the gut microbiome following colonization with human feces determines colonic tumor burden.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {20}, pmid = {24967088}, issn = {2049-2618}, support = {P50 CA130810/CA/NCI NIH HHS/United States ; R01 CA166879/CA/NCI NIH HHS/United States ; R01 GM099514/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: A growing body of evidence indicates that the gut microbiome plays a role in the development of colorectal cancer (CRC). Patients with CRC harbor gut microbiomes that are structurally distinct from those of healthy individuals; however, without the ability to track individuals during disease progression, it has not been possible to observe changes in the microbiome over the course of tumorigenesis. Mouse models have demonstrated that these changes can further promote colonic tumorigenesis. However, these models have relied upon mouse-adapted bacterial populations and so it remains unclear which human-adapted bacterial populations are responsible for modulating tumorigenesis.<br><br>RESULTS: We transplanted fecal microbiota from three CRC patients and three healthy individuals into germ-free mice, resulting in six structurally distinct microbial communities. Subjecting these mice to a chemically induced model of CRC resulted in different levels of tumorigenesis between mice. Differences in the number of tumors were strongly associated with the baseline microbiome structure in mice, but not with the cancer status of the human donors. Partitioning of baseline communities into enterotypes by Dirichlet multinomial mixture modeling resulted in three enterotypes that corresponded with tumor burden. The taxa most strongly positively correlated with increased tumor burden were members of the Bacteroides, Parabacteroides, Alistipes, and Akkermansia, all of which are Gram-negative. Members of the Gram-positive Clostridiales, including multiple members of Clostridium Group XIVa, were strongly negatively correlated with tumors. Analysis of the inferred metagenome of each community revealed a negative correlation between tumor count and the potential for butyrate production, and a positive correlation between tumor count and the capacity for host glycan degradation. Despite harboring distinct gut communities, all mice underwent conserved structural changes over the course of the model. The extent of these changes was also correlated with tumor incidence.<br><br>CONCLUSION: Our results suggest that the initial structure of the microbiome determines susceptibility to colonic tumorigenesis. There appear to be opposing roles for certain Gram-negative (Bacteroidales and Verrucomicrobia) and Gram-positive (Clostridiales) bacteria in tumor susceptibility. Thus, the impact of community structure is potentially mediated by the balance between protective, butyrate-producing populations and inflammatory, mucin-degrading populations.}, }
@article {pmid24966611, year = {2014}, author = {Zanella Terrier, MC and Simonet, ML and Bichard, P and Frossard, JL}, title = {Recurrent Clostridium difficile infections: the importance of the intestinal microbiota.}, journal = {World journal of gastroenterology}, volume = {20}, number = {23}, pages = {7416-7423}, pmid = {24966611}, issn = {2219-2840}, mesh = {Anti-Bacterial Agents/adverse effects ; Biological Therapy/adverse effects/methods ; Clostridioides difficile/*pathogenicity ; Enterocolitis, Pseudomembranous/diagnosis/*microbiology/therapy ; Feces/microbiology ; Humans ; Intestines/drug effects/*microbiology ; *Microbiota/drug effects ; Recurrence ; Risk Factors ; Treatment Outcome ; Virulence ; }, abstract = {Clostridium difficile infections (CDI) are a leading cause of antibiotic-associated and nosocomial diarrhea. Despite effective antibiotic treatments, recurrent infections are common. With the recent emergence of hypervirulent isolates of C. difficile, CDI is a growing epidemic with higher rates of recurrence, increasing severity and mortality. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach. FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI. Since the first reported use of FMT for recurrent CDI in 1958, systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment. This article focuses on current guidelines for CDI treatment, the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy, adverse effects and acceptability.}, }
@article {pmid24959769, year = {2014}, author = {Bednarska, M and Bajer, A and Siński, E and Wolska-Kuśnierz, B and Samoliński, B and Graczyk, TK}, title = {Occurrence of intestinal microsporidia in immunodeficient patients in Poland.}, journal = {Annals of agricultural and environmental medicine : AAEM}, volume = {21}, number = {2}, pages = {244-248}, doi = {10.5604/1232-1966.1108584}, pmid = {24959769}, issn = {1898-2263}, mesh = {Adult ; Child ; Feces/parasitology ; Female ; Humans ; Immunologic Deficiency Syndromes/*complications/etiology ; Intestines/*parasitology ; Male ; Microsporidia/*isolation &amp; purification ; Microsporidiosis/*epidemiology/*parasitology ; Middle Aged ; Poland/epidemiology ; Polymerase Chain Reaction ; Prevalence ; Transplant Recipients ; Young Adult ; }, abstract = {Microsporidial infections may be asymptomatic in immunocompetent hosts, but can be severe and disseminated in HIV/AIDS patients, children, the elderly, or in immunocompromised individuals, including those with primary or medically-induced immunodeficiencies. 209 faecal samples were collected from 80 clinical patients, with or without abdominal symptoms, and tested for the presence of the parasites. Microsporidia were found in 10 of the 80 patients (12.5%) using trichrom staining of faecal smears and/or PCR. Encephalitozoon intestinalis and 1 unidentified species were identified in 2 of the 32 children with primary immunodeficiencies (6%), presenting with diarrhoea, including one co-infection with Cryptosporidium meleagridis. In the group of patients with medically-induced immunosuppression (transplant recipients), 8 of the 48 patients (17%) were tested positive for microsporidia. Thus, these pathogens should be taken into account when the other etiological agents cannot be found in diarrheic patients with PIDs or undergoing immunosuppressive treatment before or after transplantation. This article presents the results of the first epidemiological study on the occurrence and prevalence of microsporidia in patients with primary and secondary immunodeficiency in Poland.}, }
@article {pmid24953716, year = {2014}, author = {Actis, GC}, title = {The gut microbiome.}, journal = {Inflammation &amp; allergy drug targets}, volume = {13}, number = {4}, pages = {217-223}, doi = {10.2174/1871528113666140623113221}, pmid = {24953716}, issn = {2212-4055}, mesh = {Animals ; Diet ; Escherichia coli/drug effects/growth &amp; development ; Gastrointestinal Tract/drug effects/*microbiology ; Humans ; Inflammation/drug therapy/microbiology ; Intestinal Mucosa/microbiology ; Microbiota/*physiology ; Obesity/microbiology ; Probiotics/pharmacology ; }, abstract = {Since the discovery and use of the microscope in the 17(th) century, we know that we host trillions of micro-organisms mostly in the form of bacteria indwelling the "barrier organs" skin, gut, and airways. They exert regulatory functions, are in a continuous dialogue with the intestinal epithelia, influence energy handling, produce nutrients, and may cause diabetes and obesity. The human microbiome has developed by modulating or avoiding inflammatory responses; the host senses bacterial presence through cell surface sensors (the Toll-like receptors) as well as by refining mucous barriers as passive defense mechanisms. The cell density and composition of the microbiome are variable and multifactored. The way of delivery establishes the type of initial flora; use of antibiotics is another factor; diet composition after weaning will shape the adult's microbiome composition, depending on the subject's life-style. Short-chain fatty acids participate in the favoring action exerted by microbiome in the pathogenesis of type-2 diabetes and obesity. Clinical observation has pinpointed a sharp rise of various dysimmune conditions in the last decades, including IBD and rheumatoid arthritis, changes that outweigh the input of simple heritability. It is nowadays proposed that the microbiome, incapable to keep up with the changes of our life-style and feeding sources in the past few decades might have contributed to these immune imbalances, finding itself inadequate to handle the changed gut environment. Another pathway to pathology is the rise of directly pathogenic phyla within a given microbiome: growth of adherent E. coli, of C. concisus, and of C. jejuni, might be examples of causes of local enteropathy, whereas the genus Prevotella copri is now suspected to be linked to rise of arthritic disorders. Inflammasomes are required to shape a non colitogenic flora. Treatment of IBD and infectious enteritides by the use of fecal transplant is warranted by this knowledge.}, }
@article {pmid24953658, year = {2014}, author = {Ji, Y and Sun, S and Goodrich, JK and Kim, H and Poole, AC and Duhamel, GE and Ley, RE and Qi, L}, title = {Diet-induced alterations in gut microflora contribute to lethal pulmonary damage in TLR2/TLR4-deficient mice.}, journal = {Cell reports}, volume = {8}, number = {1}, pages = {137-149}, pmid = {24953658}, issn = {2211-1247}, support = {T32 GM007617/GM/NIGMS NIH HHS/United States ; R21 AA020351/AA/NIAAA NIH HHS/United States ; R21 AI085332/AI/NIAID NIH HHS/United States ; DP2 OD007444/OD/NIH HHS/United States ; R01DK082582/DK/NIDDK NIH HHS/United States ; R21AI085332/AI/NIAID NIH HHS/United States ; R01 DK082582/DK/NIDDK NIH HHS/United States ; 59107338/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Diet, High-Fat/*adverse effects ; Dysbiosis/*complications/etiology/immunology ; Immunity, Innate ; Intestines/immunology/microbiology ; Lung Diseases/*etiology/pathology ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Toll-Like Receptor 2/*deficiency/genetics ; Toll-Like Receptor 4/*deficiency/genetics ; }, abstract = {Chronic intake of Western diet has driven an epidemic of obesity and metabolic syndrome, but how it induces mortality remains unclear. Here, we show that chronic intake of a high-fat diet (HFD), not a low-fat diet, leads to severe pulmonary damage and mortality in mice deficient in Toll-like receptors 2 and 4 (DKO). Diet-induced pulmonary lesions are blocked by antibiotic treatment and are transmissible to wild-type mice upon either cohousing or fecal transplantation, pointing to the existence of bacterial pathogens. Indeed, diet and innate deficiency exert significant impact on gut microbiota composition. Thus, chronic intake of HFD promotes severe pulmonary damage and mortality in DKO mice in part via gut dysbiosis, a finding that may be important for immunodeficient patients, particularly those on chemotherapy or radiotherapy, where gut-microbiota-caused conditions are often life threatening.}, }
@article {pmid24953233, year = {2014}, author = {Allen, HK and Trachsel, J and Looft, T and Casey, TA}, title = {Finding alternatives to antibiotics.}, journal = {Annals of the New York Academy of Sciences}, volume = {1323}, number = {}, pages = {91-100}, doi = {10.1111/nyas.12468}, pmid = {24953233}, issn = {1749-6632}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Humans ; Intestines/microbiology ; Microbiota ; }, abstract = {The spread of antibiotic-resistant pathogens requires new treatments. As the rate of development of new antibiotics has severely declined, alternatives to antibiotics must be considered in both animal agriculture and human medicine. Products for disease prevention are different from those for disease treatment, and examples of both are discussed here. For example, modulating the gut microbial community, either through feed additives or fecal transplantation, could be a promising way to prevent certain diseases; for disease treatment, non-antibiotic approaches include phage therapy, phage lysins, bacteriocins, and predatory bacteria. Interestingly, several of these methods augment antibiotic efficacy by improving bacterial killing and decreasing antibiotic resistance selection. Because bacteria can ultimately evolve resistance to almost any therapeutic agent, it is important to continue to use both antibiotics and their alternatives judiciously.}, }
@article {pmid24949617, year = {2014}, author = {Dumitru, IM and Dumitru, E and Resul, G and Curtali, L and Paris, S and Rugina, S}, title = {Concomitant CMV and Clostridium difficile colitis in an immunocompetent patient treated with Ganciclovir and fecal transplantation.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {23}, number = {2}, pages = {221-222}, pmid = {24949617}, issn = {1842-1121}, mesh = {Antiviral Agents/*therapeutic use ; *Clostridioides difficile ; Combined Modality Therapy ; Cytomegalovirus Infections/*therapy ; Enterocolitis, Pseudomembranous/*therapy ; Feces/microbiology ; Ganciclovir/*therapeutic use ; Humans ; Immunocompetence ; Male ; Middle Aged ; Tissue Transplantation/methods ; }, }
@article {pmid24943763, year = {2014}, author = {Gautam, N and Khurana, S and Sharma, A and Sehgal, R}, title = {Isosporiasis in a tertiary care center of North India.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {57}, number = {2}, pages = {272-274}, doi = {10.4103/0377-4929.134707}, pmid = {24943763}, issn = {0974-5130}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; Cross Infection/*epidemiology/parasitology ; Feces/parasitology ; Female ; Humans ; Immunocompromised Host ; India ; Isosporiasis/*epidemiology/parasitology ; Male ; Middle Aged ; Prevalence ; Sarcocystidae/*isolation &amp; purification ; Tertiary Care Centers ; Young Adult ; }, abstract = {BACKGROUND: Cystoisospora (Isospora) belli is a coccidian, protozoan parasite that resides in the gastrointestinal tract of humans. It is mainly reported from HIV-positive individuals. However, a few cases have been reported in other immunosuppressed individuals including renal transplant patients, and those with lymphoma and leukemia.<br><br>MATERIALS AND METHODS: During a period of 5 years (2008-2012), approximately 1700 stool samples of immunosuppressed patients were screened for the presence of opportunistic parasitic infections by a modified acid fast staining technique.<br><br>RESULTS: A total of 41 C. belli were reported, out of which 30 were HIV-positive individuals while 11 were HIV negative. The latter individuals were also immunosuppressed due to prolonged use of steroids or other immunosuppressive drugs. Twenty-six out of 30 HIV-positive patients and all the HIV-negative individuals with C. belli infection had diarrhea.<br><br>CONCLUSION: All immunosuppressed individuals should be examined for the presence of opportunistic coccidian parasitic infections and treated accordingly and alternatively, isolation of opportunistic parasites should trigger a hunt for immunocompromised state to reduce the morbidity and mortality in such patients.}, }
@article {pmid24939885, year = {2014}, author = {Seekatz, AM and Aas, J and Gessert, CE and Rubin, TA and Saman, DM and Bakken, JS and Young, VB}, title = {Recovery of the gut microbiome following fecal microbiota transplantation.}, journal = {mBio}, volume = {5}, number = {3}, pages = {e00893-14}, pmid = {24939885}, issn = {2150-7511}, support = {P30 DK034933/DK/NIDDK NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; U19AI090871/AI/NIAID NIH HHS/United States ; P30DK034933/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteria/classification/genetics/*isolation &amp; purification ; *Biological Therapy ; Clostridioides difficile/*physiology ; Clostridium Infections/microbiology/*therapy ; Feces/*microbiology ; Female ; Gastrointestinal Tract/microbiology ; Humans ; Male ; *Microbiota ; Middle Aged ; Molecular Sequence Data ; Phylogeny ; }, abstract = {UNLABELLED: Clostridium difficile infection is one of the most common health care-associated infections, and up to 40% of patients suffer from recurrence of disease following standard antibiotic therapy. Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection. It is hypothesized that FMT aids in recovery of a microbiota capable of colonization resistance to C. difficile. However, it is not fully understood how this occurs. Here we investigated changes in the fecal microbiota structure following FMT in patients with recurrent C. difficile infection, and imputed a hypothetical functional profile based on the 16S rRNA profile using a predictive metagenomic tool. Increased relative abundance of Bacteroidetes and decreased abundance of Proteobacteria were observed following FMT. The fecal microbiota of recipients following transplantation was more diverse and more similar to the donor profile than the microbiota prior to transplantation. Additionally, we observed differences in the imputed metagenomic profile. In particular, amino acid transport systems were overrepresented in samples collected prior to transplantation. These results suggest that functional changes accompany microbial structural changes following this therapy. Further identification of the specific community members and functions that promote colonization resistance may aid in the development of improved treatment methods for C. difficile infection.<br><br>IMPORTANCE: Within the last decade, Clostridium difficile infection has surpassed other bacterial infections to become the leading cause of nosocomial infections. Antibiotic use, which disrupts the gut microbiota and its capability in providing colonization resistance against C. difficile, is a known risk factor in C. difficile infection. In particular, recurrent C. difficile remains difficult to treat with standard antibiotic therapy. Fecal microbiota transplantation (FMT) has provided a successful treatment method for some patients with recurrent C. difficile infection, but its mechanism and long-term effects remain unknown. Our results provide insight into the structural and potential metabolic changes that occur following FMT, which may aid in the development of new treatment methods for C. difficile infection.}, }
@article {pmid24939656, year = {2014}, author = {Taur, Y and Jenq, RR and Perales, MA and Littmann, ER and Morjaria, S and Ling, L and No, D and Gobourne, A and Viale, A and Dahi, PB and Ponce, DM and Barker, JN and Giralt, S and van den Brink, M and Pamer, EG}, title = {The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation.}, journal = {Blood}, volume = {124}, number = {7}, pages = {1174-1182}, pmid = {24939656}, issn = {1528-0020}, support = {1R01 AI42135/AI/NIAID NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; K23 AI095398/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; 1K23AI095398-01/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification/genetics ; Feces/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; *Genetic Variation ; Hematopoietic Stem Cell Transplantation/*methods/mortality ; Humans ; Kaplan-Meier Estimate ; Male ; Microbiota/*genetics ; Middle Aged ; Multivariate Analysis ; Outcome Assessment, Health Care/methods/statistics &amp; numerical data ; Phylogeny ; Prognosis ; Proportional Hazards Models ; RNA, Ribosomal, 16S/genetics ; Survival Rate ; Transplantation, Homologous ; }, abstract = {Highly diverse bacterial populations inhabit the gastrointestinal tract and modulate host inflammation and promote immune tolerance. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal microbiota with reduced diversity. We examined the impact of intestinal diversity on subsequent mortality outcomes following transplantation. Fecal specimens were collected from 80 recipients of allo-HSCT at the time of stem cell engraftment. Bacterial 16S rRNA gene sequences were characterized, and microbial diversity was estimated using the inverse Simpson index. Subjects were classified into high, intermediate, and low diversity groups and assessed for differences in outcomes. Mortality outcomes were significantly worse in patients with lower intestinal diversity; overall survival at 3 years was 36%, 60%, and 67% for low, intermediate, and high diversity groups, respectively (P = .019, log-rank test). Low diversity showed a strong effect on mortality after multivariate adjustment for other clinical predictors (transplant related mortality: adjusted hazard ratio, 5.25; P = .014). In conclusion, the diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HSCT recipients. These results indicate that the intestinal microbiota may be an important factor in the success or failure in allo-HSCT.}, }
@article {pmid24937032, year = {2014}, author = {Kerckhof, FM and Courtens, EN and Geirnaert, A and Hoefman, S and Ho, A and Vilchez-Vargas, R and Pieper, DH and Jauregui, R and Vlaeminck, SE and Van de Wiele, T and Vandamme, P and Heylen, K and Boon, N}, title = {Optimized cryopreservation of mixed microbial communities for conserved functionality and diversity.}, journal = {PloS one}, volume = {9}, number = {6}, pages = {e99517}, pmid = {24937032}, issn = {1932-6203}, mesh = {Autotrophic Processes ; *Biofilms ; *Cryopreservation ; Cryoprotective Agents/*pharmacology ; Euryarchaeota/genetics/growth &amp; development ; Feces/microbiology ; Humans ; Microbial Viability ; *Microbiota ; Phylogeny ; Probiotics ; }, abstract = {The use of mixed microbial communities (microbiomes) for biotechnological applications has steadily increased over the past decades. However, these microbiomes are not readily available from public culture collections, hampering their potential for widespread use. The main reason for this lack of availability is the lack of an effective cryopreservation protocol. Due to this critical need, we evaluated the functionality as well as the community structure of three different types of microbiomes before and after cryopreservation with two cryoprotective agents (CPA). Microbiomes were selected based upon relevance towards applications: (1) a methanotrophic co-culture (MOB), with potential for mitigation of greenhouse gas emissions, environmental pollutants removal and bioplastics production; (2) an oxygen limited autotrophic nitrification/denitrification (OLAND) biofilm, with enhanced economic and ecological benefits for wastewater treatment, and (3) fecal material from a human donor, with potential applications for fecal transplants and pre/probiotics research. After three months of cryopreservation at -80 °C, we found that metabolic activity, in terms of the specific activity recovery of MOB, aerobic ammonium oxidizing bacteria (AerAOB) and anaerobic AOB (AnAOB, anammox) in the OLAND mixed culture, resumes sooner when one of our selected CPA [dimethyl sulfoxide (DMSO) and DMSO plus trehalose and tryptic soy broth (DMSO+TT)] was added. However, the activity of the fecal community was not influenced by the CPA addition, although the preservation of the community structure (as determined by 16S rRNA gene sequencing) was enhanced by addition of CPA. In summary, we have evaluated a cryopreservation protocol that succeeded in preserving both community structure and functionality of value-added microbiomes. This will allow individual laboratories and culture collections to boost the use of microbiomes in biotechnological applications.}, }
@article {pmid24934038, year = {2014}, author = {Oberhofer, E}, title = {[Clostridium associated diarrhea. Feces of healthy probands eliminates the troublesome intestinal pathogen].}, journal = {MMW Fortschritte der Medizin}, volume = {156}, number = {2}, pages = {22}, pmid = {24934038}, issn = {1438-3276}, mesh = {*Clostridioides difficile ; Cross Infection/epidemiology/therapy ; Cross-Sectional Studies ; Diarrhea/epidemiology/*therapy ; Enterocolitis, Pseudomembranous/epidemiology/*therapy ; *Feces ; Germany ; Humans ; Intubation, Gastrointestinal ; Probiotics/administration &amp; dosage ; *Transplants ; }, }
@article {pmid24930164, year = {2014}, author = {Nau, JY}, title = {[Fecal microbiota transplantation: details of the first French tests].}, journal = {Revue medicale suisse}, volume = {10}, number = {430}, pages = {1094-1095}, pmid = {24930164}, issn = {1660-9379}, mesh = {Feces/*microbiology ; France ; Humans ; Intestines/*microbiology ; Transplantation/methods ; }, }
@article {pmid24927151, year = {2014}, author = {Honda, H and Dubberke, ER}, title = {Clostridium difficile infection in solid organ transplant recipients.}, journal = {Current opinion in infectious diseases}, volume = {27}, number = {4}, pages = {336-341}, doi = {10.1097/QCO.0000000000000075}, pmid = {24927151}, issn = {1473-6527}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Humans ; *Transplant Recipients ; }, abstract = {PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections, and the threat associated with CDI continues to grow in all patient populations. There is increasing evidence that CDI has a substantial impact on the morbidity and mortality in solid organ transplant (SOT) recipients. Furthermore, new diagnostic and treatment options and strategies for CDI have emerged over the last decade. The purpose of this review is to provide a general understanding of CDI and its evidence-based diagnosis and management strategies, with a focus on SOT recipients.<br><br>RECENT FINDINGS: The incidence and severity of CDI have significantly increased since the year 2000. Studies have identified novel risk factors for CDI, and a new epidemic strain, the NAP1/BI/027, has emerged. Despite the development of newer testing methods and approaches, including nucleic acid amplification tests and testing algorithms, the optimal method for diagnosing CDI is an area of controversy. New agents for treating CDI are being developed, and the use of fecal microbiota transplantation to treat recurrent CDI in SOT recipients is also evolving.<br><br>SUMMARY: CDI is a significant problem for SOT recipients. Further studies on diagnostic and therapeutic strategies with a focus on SOT recipients are needed to further improve patient outcomes.}, }
@article {pmid24922509, year = {2014}, author = {De Angelis, M and Montemurno, E and Piccolo, M and Vannini, L and Lauriero, G and Maranzano, V and Gozzi, G and Serrazanetti, D and Dalfino, G and Gobbetti, M and Gesualdo, L}, title = {Microbiota and metabolome associated with immunoglobulin A nephropathy (IgAN).}, journal = {PloS one}, volume = {9}, number = {6}, pages = {e99006}, pmid = {24922509}, issn = {1932-6203}, mesh = {Adult ; Case-Control Studies ; Female ; Glomerulonephritis, IGA/*microbiology ; Humans ; Male ; *Metabolome ; *Microbiota ; Middle Aged ; }, abstract = {This study aimed at investigating the fecal microbiota, and the fecal and urinary metabolome of non progressor (NP) and progressor (P) patients with immunoglobulin A nephropathy (IgAN). Three groups of volunteers were included in the study: (i) sixteen IgAN NP patients; (ii) sixteen IgAN P patients; and (iii) sixteen healthy control (HC) subjects, without known diseases. Selective media were used to determine the main cultivable bacterial groups. Bacterial tag-encoded FLX-titanium amplicon pyrosequencing of the 16S rDNA and 16S rRNA was carried out to determine total and metabolically active bacteria, respectively. Biochrom 30 series amino acid analyzer and gas-chromatography mass spectrometry/solid-phase microextraction (GC-MS/SPME) analyses were mainly carried out for metabolomic analyses. As estimated by rarefaction, Chao and Shannon diversity index, the lowest microbial diversity was found in P patients. Firmicutes increased in the fecal samples of NP and, especially, P patients due to the higher percentages of some genera/species of Ruminococcaceae, Lachnospiraceae, Eubacteriaceae and Streptococcaeae. With a few exceptions, species of Clostridium, Enterococcus and Lactobacillus genera were found at the highest levels in HC. Bacteroidaceae, Porphyromonadaceae, Prevotellaceae and Rikenellaceae families differed among NP, P and HC subjects. Sutterellaceae and Enterobacteriaceae species were almost the highest in the fecal samples of NP and/or P patients. Compared to HC subjects, Bifidobacterium species decreased in the fecal samples of NP and P. As shown by multivariate statistical analyses, the levels of metabolites (free amino acids and organic volatile compounds) from fecal and urinary samples markedly differentiated NP and, especially, P patients.}, }
@article {pmid24919374, year = {2013}, author = {Michot, F}, title = {[Surgery for anal incontinence: developments in the past two decades and future directions].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {197}, number = {2}, pages = {457-67; discussion 467-8}, pmid = {24919374}, issn = {0001-4079}, mesh = {Anal Canal/innervation/surgery ; Digestive System Surgical Procedures/methods/*trends ; Electric Stimulation Therapy ; Electrodes, Implanted ; Fecal Incontinence/*therapy ; Humans ; Muscle, Skeletal/transplantation ; }, abstract = {Studies showing the frequency of anal incontinence and its social and economic impact have driven progress in surgical treatment, from muscle repair by myorraphy (mainly posterior myorraphy) or sphincteroplasty by direct suture of the external anal sphincter some 20 years ago, to invasive surgery with implantation of an artificial anal sphincter in 1993, mini-invasive surgery based on sacral nerve stimulation in 1998, failure of mini-invasive procedures with injection of a bulking agent or radiofrequency in 2000-2010, and development in 2012 of cellular therapy based on injection of autologous myoblasts. Progress in functional gut exploration (anorectal manometry, electrophysiological tests, endoanal ultrasonography, MRI, colonic transit time) and better knowledge of colonic and ano-rectal physiology will lead to further surgical advances.}, }
@article {pmid24917658, year = {2014}, author = {Bakken, JS}, title = {Staggered and tapered antibiotic withdrawal with administration of kefir for recurrent Clostridium difficile infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {59}, number = {6}, pages = {858-861}, doi = {10.1093/cid/ciu429}, pmid = {24917658}, issn = {1537-6591}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; Clostridioides difficile ; *Cultured Milk Products ; Drug Administration Schedule ; Enterocolitis, Pseudomembranous/*therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Probiotics/*administration &amp; dosage ; Prospective Studies ; Treatment Outcome ; }, abstract = {Daily administration of the probiotic kefir given in combination with a staggered and tapered antibiotic withdrawal regimen may resolve recurrent Clostridium difficile infection as effectively as fecal microbiota transplantation.}, }
@article {pmid24912733, year = {2014}, author = {Otto, J and Busch, D and Klink, C and Ciritsis, A and Woitok, A and Kuhl, C and Klinge, U and Neumann, UP and Kraemer, NA and Conze, J}, title = {In vivo MRI visualization of parastomal mesh in a porcine model.}, journal = {Hernia : the journal of hernias and abdominal wall surgery}, volume = {18}, number = {5}, pages = {663-670}, pmid = {24912733}, issn = {1248-9204}, mesh = {Animals ; Biocompatible Materials ; Disease Models, Animal ; *Enterostomy ; Feasibility Studies ; Ferric Compounds ; Laparoscopy ; *Magnetic Resonance Imaging ; Male ; Membranes, Artificial ; Polyvinyls ; *Surgical Mesh ; Swine ; }, abstract = {INTRODUCTION: After two-dimensional plane MRI-visible mesh implants could be successfully visualized in phantom and small animal model, the aim of the underlying study was to explore the feasibility of an MRI visualization of complex three-dimensional mesh geometry in close contact to the intestine. We therefore used a MR-visible three-dimensional intra-peritoneal stoma (IPST) mesh in a porcine model.<br><br>MATERIALS AND METHODS: Laparoscopic terminal sigmoid colostomy has been done with implantation of a prophylactic MRI-visible IPST mesh in two animals. MRI investigations were done after 1&#xa0;week, 6&#xa0;months and in case of clinical impairment. These findings were compared to endoscopy and makroscopical and histological investigation of the preparation.<br><br>RESULTS: The first animal has to be killed because of an ileus 4&#xa0;weeks after operation. The second animal has to be killed after 7&#xa0;weeks because of recurrent obstipation. In all cases MRI investigation could identify the IPST mesh and could clearly separate between mesh and intestine. MRI revealed a big bowl ileus due to a funnel dislocation in the first animal. In the second animal, MR diagnostic explored a functional stenosis because of a too small diameter of the central funnel in combination with sticky feces and distension of the terminal sigmoid before discharging into the funnel. Endoscopy, makroscopical and histological investigation of the preparation supported MRI findings.<br><br>CONCLUSION: Although complicate clinical course was a diagnostic challenge exploring 3D implants such as IPST, visualization of this new MRI-visible IPST mesh could be proved and turned out as an effective diagnostic possibility. Further studies are necessary to analyze long-time effects such as shrinkage, mesh migration and tissue integration using MRI scanning.}, }
@article {pmid24909808, year = {2014}, author = {Ianiro, G and Bibbò, S and Gasbarrini, A and Cammarota, G}, title = {Therapeutic modulation of gut microbiota: current clinical applications and future perspectives.}, journal = {Current drug targets}, volume = {15}, number = {8}, pages = {762-770}, doi = {10.2174/1389450115666140606111402}, pmid = {24909808}, issn = {1873-5592}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Autistic Disorder/microbiology/therapy ; Clinical Trials as Topic ; Digestive System Diseases/microbiology/therapy ; Fatigue Syndrome, Chronic/microbiology/therapy ; Feces/*microbiology ; Gastrointestinal Tract/drug effects/*microbiology ; Humans ; Hypersensitivity/microbiology/therapy ; Microbiota/*drug effects ; Obesity/microbiology/therapy ; Probiotics/*therapeutic use ; }, abstract = {Human beings and gut microbiota are in a symbiotic relationship, and the hypothesis of a "super organism" composed of the human organism and microbes has been recently proposed. The gut microbiota fulfills important metabolic and immunological tasks, and the impairment of its composition might alter homeostasis and lead to the development of microbiota-related diseases. The most common illnesses associated with alterations of the gut microbiota include inflammatory bowel disease, gastroenteric infections, irritable bowel syndrome and other gastrointestinal functional diseases, colorectal cancer, metabolic syndrome and obesity, liver diseases, allergic diseases, and neurological diseases such as autism. In theory, every disease associated with the impairment of intestinal microflora might benefit from the therapeutic modulation of the gut microbiota. A number of attempts to manipulate the microbiota have not produced identical results for every disease. Although antibiotics and probiotics have been available for a long time, the so-called fecal microbiota transplantation, which is a very old remedy, was only recently re-evaluated as a promising therapeutic approach for microbiota impairment. A comprehensive understanding of the gut microbiota composition, in states of both health and various diseases, is needed for the development of future approaches for microbiota modulation and for developing targeted therapies. In this review, we describe the role of the microbiota in several diseases and the related treatment options that are currently available.}, }
@article {pmid24908572, year = {2014}, author = {Senore, C and Reggio, D and Musso, A and Bruno, M and De Angelis, C and Giordanino, C and Coppo, C and Tari, R and Pagliarulo, M and Carmagnola, S and Montino, F and Silvani, M and Segnan, N and Rizzetto, M and Saracco, GM}, title = {Narrow band imaging vs. high definition colonoscopy for detection of colorectal adenomas in patients with positive faecal occult blood test: a randomised trial.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {46}, number = {9}, pages = {803-807}, doi = {10.1016/j.dld.2014.05.007}, pmid = {24908572}, issn = {1878-3562}, mesh = {Adenoma/*diagnosis/epidemiology ; Aged ; Colonoscopy/*methods ; Colorectal Neoplasms/*diagnosis/epidemiology ; Female ; Follow-Up Studies ; Humans ; Image Processing, Computer-Assisted ; Incidence ; Italy/epidemiology ; Male ; Mass Screening/*methods ; Narrow Band Imaging/*methods ; *Occult Blood ; Prospective Studies ; }, abstract = {BACKGROUND: The impact of narrow band imaging in improving the adenoma detection rate in a screening scenario is still unclear.<br><br>AIM: To evaluate whether narrow band imaging compared with high definition white light colonoscopy can enhance the adenoma detection rate during screening colonoscopy.<br><br>METHODS: Consecutive patients presenting for screening colonoscopy were included into this study and were randomly assigned to the narrow band imaging group (Group 1) or standard colonoscopy group (Group 2). Primary end point was the adenoma detection rate and secondary aim was the detection rate of advanced adenomas.<br><br>RESULTS: Overall, 117 patients were allocated to Group 1 and 120 to Group 2. Both the adenoma detection rate and the detection rate of advanced adenomas were not significantly different between the two groups (respectively, 52.1% vs. 55%, RR=0.95, 95% CI 0.75-1.20; 32.5% vs. 44.2%, RR=0.74, 95% CI 0.53-1.02). No significant difference between the proportions of polypoid and flat adenomas was found. Male gender, no prior history of screening, and endoscopist's adenoma detection rate were independent predictive factors of higher advanced adenoma detection rate.<br><br>CONCLUSIONS: In a screening scenario, narrow band imaging did not improve the adenoma nor advanced adenoma detection rates compared to high definition white light colonoscopy.}, }
@article {pmid24903435, year = {2014}, author = {Ianiro, G and Gasbarrini, A and Cammarota, G}, title = {Letter: Faecal microbiota transplantation--not a one-size-fits-all approach.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {40}, number = {1}, pages = {119}, doi = {10.1111/apt.12783}, pmid = {24903435}, issn = {1365-2036}, mesh = {Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; Inflammatory Bowel Diseases/*therapy ; }, }
@article {pmid24903434, year = {2014}, author = {Sha, S and Wu, K}, title = {Letter: Faecal microbiota transplantation--not a one-size-fits-all approach; authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {40}, number = {1}, pages = {119-120}, doi = {10.1111/apt.12801}, pmid = {24903434}, issn = {1365-2036}, mesh = {Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; Inflammatory Bowel Diseases/*therapy ; }, }
@article {pmid24902394, year = {2013}, author = {Bookstaver, PB and Ahmed, Y and Millisor, VE and Siddiqui, W and Albrecht, H}, title = {Clostridium difficile: case report and concise review of fecal microbiota transplantation.}, journal = {Journal of the South Carolina Medical Association (1975)}, volume = {109}, number = {2}, pages = {62-66}, pmid = {24902394}, issn = {0038-3139}, mesh = {Anti-Bacterial Agents/therapeutic use ; Biological Therapy/*methods ; Clostridioides difficile/isolation &amp; purification/*pathogenicity ; Enterocolitis, Pseudomembranous/diagnosis/drug therapy/*microbiology ; Feces/*microbiology ; Female ; Humans ; Intestines/*microbiology ; *Microbiota ; Middle Aged ; Patient Isolation ; Transplantation/*methods ; }, }
@article {pmid24893981, year = {2014}, author = {Alonso, CD and Kamboj, M}, title = {Clostridium difficile Infection (CDI) in Solid Organ and Hematopoietic Stem Cell Transplant Recipients.}, journal = {Current infectious disease reports}, volume = {16}, number = {8}, pages = {414}, pmid = {24893981}, issn = {1523-3847}, abstract = {Patients undergoing solid organ and stem cell transplantation are at increased risk of Clostridium difficile infection (CDI) compared with nontransplant patients. CDI may be associated with significant morbidity in this population including prolonged hospitalization, increased hospital charges, and complications in the transplanted organ. A combination of host factors, including both B-cell and T-cell immunosuppression, in addition to traditional risk factors for CDI such as broad-spectrum antibacterial exposure, are likely to contribute to the elevated risk in this population. This article addresses the current epidemiology and risk factors for CDI in transplant recipients, the downstream complications following this infection, and current management strategies, with an emphasis on novel approaches for primary and recurrent disease including fecal microbiota transplantation.}, }
@article {pmid24891996, year = {2014}, author = {LeBeau, S and Khoruts, A}, title = {Fecal microbiota transplantation: an interview with alexander khoruts.}, journal = {Global advances in health and medicine}, volume = {3}, number = {3}, pages = {73-80}, pmid = {24891996}, issn = {2164-957X}, }
@article {pmid24890442, year = {2014}, author = {Kelly, CR and Ihunnah, C and Fischer, M and Khoruts, A and Surawicz, C and Afzali, A and Aroniadis, O and Barto, A and Borody, T and Giovanelli, A and Gordon, S and Gluck, M and Hohmann, EL and Kao, D and Kao, JY and McQuillen, DP and Mellow, M and Rank, KM and Rao, K and Ray, A and Schwartz, MA and Singh, N and Stollman, N and Suskind, DL and Vindigni, SM and Youngster, I and Brandt, L}, title = {Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients.}, journal = {The American journal of gastroenterology}, volume = {109}, number = {7}, pages = {1065-1071}, pmid = {24890442}, issn = {1572-0241}, support = {R21 AI091907/AI/NIAID NIH HHS/United States ; R21 DK093839/DK/NIDDK NIH HHS/United States ; R21AI091907/AI/NIAID NIH HHS/United States ; 1R21DK093839-01A1/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*microbiology/*therapy ; Feces/*microbiology ; Female ; Humans ; *Immunocompromised Host ; Male ; *Microbiota ; Middle Aged ; Retrospective Studies ; Surveys and Questionnaires ; Treatment Outcome ; }, abstract = {OBJECTIVES: Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients.<br><br>METHODS: A multicenter retrospective series was performed on the use of FMT in IC patients with CDI that was recurrent, refractory, or severe. We aimed to describe rates of CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item questionnaire soliciting demographic and pre- and post-FMT data was completed for 99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such as death or hospitalization within 12 weeks of FMT, (iii) infection within 12 weeks of FMT, and (iv) AEs (related and unrelated) to FMT.<br><br>RESULTS: Cases included adult (75) and pediatric (5) patients treated with FMT for recurrent (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean follow-up period between FMT and data collection was 11 months (range 3-46 months). Reasons for IC included: HIV/AIDS (3), solid organ transplant (19), oncologic condition (7), immunosuppressive therapy for inflammatory bowel disease (IBD; 36), and other medical conditions/medications (15). The CDI cure rate after a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI. Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during sedation for FMT administered via colonoscopy; the other was unrelated to FMT. None suffered infections definitely related to FMT, but two patients developed unrelated infections and five had self-limited diarrheal illness in which no causal organism was identified. One patient had a superficial mucosal tear caused by the colonoscopy performed for the FMT, and three patients reported mild, self-limited abdominal discomfort post FMT. Five (14% of IBD patients) experienced disease flare post FMT. Three ulcerative colitis (UC) patients underwent colectomy related to course of UC >100 days after FMT.<br><br>CONCLUSIONS: This series demonstrates the effective use of FMT for CDI in IC patients with few SAEs or related AEs. Importantly, there were no related infectious complications in these high-risk patients.}, }
@article {pmid24875567, year = {2014}, author = {de Sèze, M and Gamé, X}, title = {[Multiple sclerosis and pelviperineology: Urinary and sexual dysfunctions and pregnancy].}, journal = {Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie}, volume = {24}, number = {8}, pages = {483-494}, doi = {10.1016/j.purol.2014.02.006}, pmid = {24875567}, issn = {1166-7087}, mesh = {Adrenergic alpha-Antagonists/therapeutic use ; Botulinum Toxins, Type A/therapeutic use ; Cannabinoids/therapeutic use ; Cystostomy ; Electric Stimulation Therapy ; Exercise Therapy ; Female ; Female Urogenital Diseases/*etiology/therapy ; Humans ; Male ; Male Urogenital Diseases/*etiology/therapy ; Multiple Sclerosis/*complications/therapy ; Neurotoxins/therapeutic use ; Phosphodiesterase 5 Inhibitors/therapeutic use ; Pregnancy ; Pregnancy Complications/*etiology ; Quality of Life ; Risk Factors ; Sensory System Agents/therapeutic use ; Sexual Dysfunctions, Psychological/*etiology/therapy ; Stents ; Urinary Catheterization ; Urodynamics ; }, abstract = {GOAL: The aim was to review the literature on genito-urinary dysfunction in multiple sclerosis (MS).<br><br>MATERIAL: A literature review through the PubMed library until August, 31 2013 was carried out using the following keywords: multiple sclerosis and neurogenic bladder, neuropathic bladder, bladder, management, follow-up, urological complications, urological treatment, sexual dysfunction, female sexual function, male sexual function, erectile dysfunction, anorectal, faecal, constipation, bowel, pregnancy, parturition, delivery, breast-feeding.<br><br>RESULTS: Genito-urinary dysfunction is frequent in MS (35-90%) and may happen soon in the disease. Urinary symptoms (10-90%) are manifold resulting in a quality of life alteration and the onset of complications in 30% of the cases requiring a long-term follow-up. Sexual dysfunctions (35-87%) are also manifold affecting all the sexuality domains in men and women. Except the phosphodiesterase V inhibitors, few treatments have been assessed in this population. Pregnancy is nowadays considered as beneficial resulting in a disease slow-down and the lack of disease worsening despite an increase in disease relapse during the post-partum first quarter. It seems to be better to consider getting pregnant after at least one year without any relapse and to emphasize an exclusive breast-feeding.<br><br>CONCLUSION: Urinary and sexual dysfunctions are frequent in MS. A transdisciplinary approach including the neurologist and pelviperineology specialists facilitates a disability adapted early management.}, }
@article {pmid24868904, year = {2014}, author = {Piekarska, M and Wandałowicz, AD and Miigoć, H}, title = {[Clostridium difficile infecion--diagnostics, prevention and treatment].}, journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego}, volume = {36}, number = {214}, pages = {278-282}, pmid = {24868904}, issn = {1426-9686}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/complications/*diagnosis/*drug therapy/prevention &amp; control ; Diarrhea/microbiology ; Feces/microbiology ; Fidaxomicin ; Humans ; Metronidazole/therapeutic use ; Probiotics/therapeutic use ; Secondary Prevention ; Vancomycin/therapeutic use ; }, abstract = {Clostridium difficile is the most common cause of an antibiotic-associated diarrhoea. Frequency of Clostridium difficile infections (CDI) increased in the last decade. This study presents current preventive measure i.e. hand washing, disposable gloves. Additionally, the article presents diagnostic methods: detection glutamine dehydrogenase (GDH), toxins A and B, cytotoxicity neutralization test, polymerase chain reaction methods (PCR) i.e. nucleic acid amplification test (NAAT) and stool culture. Moreover available methods of treatment were presented depending on severity of CDI e.i. metronidazole, vancomycin, fidaxomicin, rifaximin. Furthermore, the review provides information about alternative methods of treatment in view of new hypervirulent strains of C. difficile and increasing resistance to commonly used antibiotics, including: fuscid acid, bacitracin, probiotics, non-toxigenic strains, immunoglobulins, monoclonal antibodies, vaccines, toxins binders and fecal transplant.}, }
@article {pmid24866958, year = {2014}, author = {Schmelz, R and Hampe, J}, title = {[Fecal microbiota transplantation: when and for whom?].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {139}, number = {23}, pages = {1237-1239}, doi = {10.1055/s-0034-1370032}, pmid = {24866958}, issn = {1439-4413}, mesh = {Bacteria ; Biological Therapy ; Clostridium Infections/*microbiology/*therapy ; Complementary Therapies/methods ; Enterocolitis/*microbiology/*therapy ; *Evidence-Based Medicine ; Feces/*microbiology ; Humans ; Prebiotics ; Probiotics/administration &amp; dosage ; Transplantation/*methods ; }, }
@article {pmid24861460, year = {2014}, author = {Kneist, W and Kauff, DW and Schröder, M and Koch, KP and Lang, H}, title = {Percutaneous nerve evaluation based on electrode placement under control of autonomic innervation.}, journal = {Techniques in coloproctology}, volume = {18}, number = {8}, pages = {725-730}, pmid = {24861460}, issn = {1128-045X}, mesh = {Adult ; Aged ; Anal Canal/*innervation/physiopathology ; Autonomic Nervous System/*physiopathology ; Defecation/*physiology ; *Electrodes, Implanted ; Electromyography ; Fecal Incontinence/physiopathology/*therapy ; Female ; Follow-Up Studies ; Humans ; Lumbosacral Plexus ; Male ; Middle Aged ; Prospective Studies ; Transcutaneous Electric Nerve Stimulation/*methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Foramen needle electrode placement for percutaneous nerve evaluation (PNE) is currently carried out while observing the somatic motor response. This study investigated electrode placement while observing the autonomic as well as the somatic response.<br><br>METHODS: A consecutive series of ten patients (seven women) with a median age of 51.9 (range 30-75) years undergoing PNE for faecal incontinence (n&#xa0;=&#xa0;6) and obstipation (n&#xa0;=&#xa0;4) were investigated prospectively. Electrode placement was carried out under simultaneous electromyography (EMG) of the external anal sphincter (EAS) and internal anal sphincter (IAS) and cystomanometry.<br><br>RESULTS: PNE under control of somatic and autonomic nerve responses was carried out in all patients. In three out of ten patients, initial needle electrode placement showed single evoked EMG signals from the EAS. Final electrode placement resulted in adequate somatic motor and autonomic responses in all patients. Comparison of the increases in IAS EMG amplitude on the right and left stimulation sites for sacral nerves S3 and S4 demonstrated significant differences [S3 right: median 15.3 (interquartile range (IQR) 10.4; 20.1) &#xb5;V vs. S3 left: median 11.6 (IQR 8.6; 16.0) &#xb5;V, p&#xa0;=&#xa0;0.034 and S4 right: median 24.1 (IQR 20.1; 37.2) &#xb5;V vs. S4 left: median 12.0 (IQR 10.7; 13.7) &#xb5;V, p&#xa0;=&#xa0;0.012]. Stimulation-induced bladder activation was achieved in all seven patients with concomitant urinary dysfunction.<br><br>CONCLUSIONS: Control of not just the somatic motor response but also the autonomic nerve response during foramen needle electrode placement may objectify PNE.}, }
@article {pmid24858336, year = {2016}, author = {Yu, S and Abdelkarim, A and Nawras, A and Hinch, BT and Mbaso, C and Valavoor, S and Safi, F and Hammersley, J and Tang, J and Assaly, R}, title = {Fecal Transplant for Treatment of Toxic Megacolon Associated With Clostridium Difficile Colitis in a Patient With Duchenne Muscular Dystrophy.}, journal = {American journal of therapeutics}, volume = {23}, number = {2}, pages = {e609-13}, doi = {10.1097/MJT.0000000000000062}, pmid = {24858336}, issn = {1536-3686}, mesh = {Adult ; Enterocolitis, Pseudomembranous/*complications/drug therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Motility ; Humans ; Male ; Megacolon, Toxic/*therapy ; Muscular Dystrophy, Duchenne/*complications/physiopathology ; }, abstract = {Clostridium difficile (C diff) colitis infection is the most common cause of nosocomial infectious diarrhea and the prevalence is increasing worldwide. Toxic megacolon is a severe complication of C diff colitis associated with high mortality. Gastrointestinal (GI) comorbidity and impaired smooth muscle contraction are risk factors for the development of C diff-associated toxic megacolon. We present a case of fulminant C diff colitis with toxic megacolon in a patient with Duchenne muscular dystrophy (DMD) in the intensive care unit. C diff colitis was diagnosed by clinical presentation and positive C diff DNA amplification test (polymerase chain reaction). The impairment of GI tract due to DMD predisposes these patients to severe C diff infection and toxic megacolon, as observed in this case report. For the same reason, the recovery of GI function in these patients can be prolonged. While surgery was conducted for relieving the pressure from toxic megacolon, fecal microbiota transplantation through colonoscopy resulted in successful resolution of the C diff symptoms, although the recovery is prolonged due to DMD.}, }
@article {pmid24855561, year = {2014}, author = {Shankar, V and Hamilton, MJ and Khoruts, A and Kilburn, A and Unno, T and Paliy, O and Sadowsky, MJ}, title = {Species and genus level resolution analysis of gut microbiota in Clostridium difficile patients following fecal microbiota transplantation.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {13}, pmid = {24855561}, issn = {2049-2618}, abstract = {BACKGROUND: Clostridium difficile is an opportunistic human intestinal pathogen, and C. difficile infection (CDI) is one of the main causes of antibiotic-induced diarrhea and colitis. One successful approach to combat CDI, particularly recurrent form of CDI, is through transplantation of fecal microbiota from a healthy donor to the infected patient. In this study we investigated the distal gut microbial communities of three CDI patients before and after fecal microbiota transplantation, and we compared these communities to the composition of the donor's fecal microbiota. We utilized phylogenetic Microbiota Array, high-throughput Illumina sequencing, and fluorescent in situ hybridization to profile microbiota composition down to the genus and species level resolution.<br><br>RESULTS: The original patients' microbiota had low diversity, was dominated by members of Gammaproteobacteria and Bacilli, and had low numbers of Clostridia and Bacteroidia. At the genus level, fecal samples of CDI patients were rich in members of the Lactobacillus, Streptococcus, and Enterobacter genera. In comparison, the donor community was dominated by Clostridia and had significantly higher diversity and evenness. The patients' distal gut communities were completely transformed within 3 days following fecal transplantation, and these communities remained stable in each patient for at least 4 months. Despite compositional differences among recipients' pre-treatment gut microbiota, the transplanted gut communities were highly similar among recipients post-transplantation, were indistinguishable from that of the donor, and were rich in members of Blautia, Coprococcus, and Faecalibacterium. In each case, the gut microbiota restoration led to a complete patient recovery and symptom alleviation.<br><br>CONCLUSION: We conclude that C. difficile infection can be successfully treated by fecal microbiota transplantation and that this leads to stable transformation of the distal gut microbial community from the one abundant in aerotolerant species to that dominated by members of the Clostridia.}, }
@article {pmid24853539, year = {2014}, author = {Pierog, A and Mencin, A and Reilly, NR}, title = {Fecal microbiota transplantation in children with recurrent Clostridium difficile infection.}, journal = {The Pediatric infectious disease journal}, volume = {33}, number = {11}, pages = {1198-1200}, doi = {10.1097/INF.0000000000000419}, pmid = {24853539}, issn = {1532-0987}, mesh = {*Biological Therapy/methods ; Child ; Child, Preschool ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Infant ; Male ; *Microbiota ; Recurrence ; Retreatment ; Young Adult ; }, abstract = {Clostridium difficile eradication using fecal microbiota transplantation (FMT) has been successful in adults but little information is available in pediatrics. We report 6 pediatric patients with refractory C. difficile cured by FMT with no recurrences to date. Our results demonstrate that FMT can be an effective treatment for refractory C. difficile infection in pediatrics. Long-term safety and efficacy need to be studied.}, }
@article {pmid24846637, year = {2014}, author = {Verghese, VP and Robinson, JL}, title = {A systematic review of hepatitis E virus infection in children.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {59}, number = {5}, pages = {689-697}, doi = {10.1093/cid/ciu371}, pmid = {24846637}, issn = {1537-6591}, mesh = {Adolescent ; Antibodies, Viral/blood ; Child ; Child, Preschool ; Egypt/epidemiology ; Hepatitis A/epidemiology ; Hepatitis E/diagnosis/*epidemiology/therapy/transmission ; Hepatitis E virus/immunology/pathogenicity ; Humans ; India/epidemiology ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Seroepidemiologic Studies ; Transplant Recipients ; Young Adult ; }, abstract = {A systematic review was conducted, seeking all literature relevant to the epidemiology, clinical and laboratory features, and outcome of hepatitis E virus (HEV) infection in children. Transmission is thought to be primarily from fecal-oral transmission, with the role of transmission from animal reservoirs not being clear in children. Worldwide, seroprevalence is <10% up to 10 years of age, with the exception of 1 of 5 studies from India and the sole study from Egypt. Seroprevalence increases with age, but it is not clear if it is increasing over time. The clinical presentation of HEV infection has broad similarities to hepatitis A virus (HAV) infection, with most cases being subclinical. However, HEV differs from HAV in that infectivity is lower, perinatal transmission can result in neonatal morbidity and even mortality, and a chronic carrier state exists, accounting for chronic hepatitis in some pediatric solid organ transplant recipients.}, }
@article {pmid24845223, year = {2014}, author = {Singh, R and van Nood, E and Nieuwdorp, M and van Dam, B and ten Berge, IJ and Geerlings, SE and Bemelman, FJ}, title = {Donor feces infusion for eradication of Extended Spectrum beta-Lactamase producing Escherichia coli in a patient with end stage renal disease.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {20}, number = {11}, pages = {O977-8}, doi = {10.1111/1469-0691.12683}, pmid = {24845223}, issn = {1469-0691}, mesh = {Biological Therapy/*methods ; Escherichia coli/*enzymology/isolation &amp; purification ; Escherichia coli Infections/microbiology/*therapy ; *Feces ; Humans ; Kidney Failure, Chronic/*complications ; Male ; Middle Aged ; Treatment Outcome ; beta-Lactamases/*metabolism ; }, }
@article {pmid24844698, year = {2014}, author = {Nieuwdorp, M}, title = {Faecal microbiota transplantation.}, journal = {The British journal of surgery}, volume = {101}, number = {8}, pages = {887-888}, doi = {10.1002/bjs.9549}, pmid = {24844698}, issn = {1365-2168}, mesh = {Clostridium Infections/*therapy ; Feces/*microbiology ; Humans ; Inflammatory Bowel Diseases/*therapy ; Microbiota/*physiology ; }, }
@article {pmid24843988, year = {2014}, author = {Tissot, F and Maillard, MH}, title = {[Clostridium difficile infections: update on new European recommendations].}, journal = {Revue medicale suisse}, volume = {10}, number = {427}, pages = {913-6, 918-9}, pmid = {24843988}, issn = {1660-9379}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/microbiology ; Humans ; Practice Guidelines as Topic ; Transplantation ; }, abstract = {Clostridium difficile infections: update on new European recommandations While metronidazole and vancomycin have been the only drug options to date for the treatment of C. difficile infection, new therapeutic approaches with promising results have recently emerged for the treatment of the first episode and relapses. Fidaxomicin is a new macrocyclic antibiotic more active against C. difficile and with a narrow spectrum allowing preservation of the intestinal microbiota. While having the same efficacy as vancomycin for the treatment of the first episode, this agent is associated with a lower rate of relapse. The highest relapse-free cure rate is achieved through fecal microbiota transplantation, which should be considered for patients with multiple relapses.}, }
@article {pmid24840543, year = {2014}, author = {Altomare, DF and Rockwood, T}, title = {Reply to Commentary on 'The TAPE score: a new scoring system for comprehensive evaluation of pelvic floor function' by Professor Søren Laurberg.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {16}, number = {8}, pages = {640-641}, doi = {10.1111/codi.12668}, pmid = {24840543}, issn = {1463-1318}, mesh = {Defecation/*physiology ; Fecal Incontinence/*diagnosis ; Female ; Gynecologic Surgical Procedures/*adverse effects ; Humans ; Pelvic Floor/*physiopathology ; Perineum/*physiopathology ; Urinary Incontinence/*diagnosis ; Urination/*physiology ; }, }
@article {pmid24838421, year = {2014}, author = {Hashash, JG and Binion, DG}, title = {Managing Clostridium difficile in inflammatory bowel disease (IBD).}, journal = {Current gastroenterology reports}, volume = {16}, number = {7}, pages = {393}, pmid = {24838421}, issn = {1534-312X}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*complications/diagnosis/*drug therapy/epidemiology ; Feces/microbiology ; Humans ; Inflammatory Bowel Diseases/*complications/epidemiology ; Opportunistic Infections/complications/diagnosis/drug therapy/epidemiology ; Tissue Transplantation ; Vancomycin/therapeutic use ; }, abstract = {Clostridium difficile (C. difficile) infection has emerged as a significant clinical challenge for patients suffering from inflammatory bowel disease (IBD). C. difficile can both precipitate and worsen flares of IBD, contributing to emergent colectomies and mortality. Advances in the management of C. difficile infection in IBD include recommendations for testing for this infection in the setting of clinical flare and hospitalization, improved diagnostic testing, identification of high rates of carriage and infection in pediatric IBD, and new data associating patterns of IBD genetic risk alleles with the development of this infection. Therapeutically, oral vancomycin has emerged as a superior treatment for IBD patients with moderate to severe disease compared with metronidazole. Although highly effective in the general population, fecal microbiome transplantation for recurrent C. difficile infection in IBD patients has been associated with colitis flare in the majority of patients who have received this treatment.}, }
@article {pmid24831911, year = {2013}, author = {Smith, S}, title = {Intestinal microbiota transplantation: a case of Crohn's colitis with superimposed Clostridium difficile infection.}, journal = {The West Indian medical journal}, volume = {62}, number = {7}, pages = {675-677}, doi = {10.7727/wimj.2012.231}, pmid = {24831911}, issn = {0043-3144}, mesh = {Addison Disease/complications ; Adult ; Anti-Infective Agents/therapeutic use ; Clostridioides difficile/pathogenicity ; Crohn Disease/*complications/immunology/therapy ; Enterocolitis, Pseudomembranous/complications/immunology/*therapy ; Fatal Outcome ; Feces/*microbiology ; Female ; Humans ; Intestines/*microbiology ; Metagenome ; Metronidazole/therapeutic use ; Microbiota ; Superinfection ; Vancomycin/therapeutic use ; }, }
@article {pmid24828871, year = {2015}, author = {Trubiano, JA and George, A and Barnett, J and Siwan, M and Heriot, A and Prince, HM and Slavin, MA and Teh, BW}, title = {A different kind of "allogeneic transplant": successful fecal microbiota transplant for recurrent and refractory Clostridium difficile infection in a patient with relapsed aggressive B-cell lymphoma.}, journal = {Leukemia &amp; lymphoma}, volume = {56}, number = {2}, pages = {512-514}, doi = {10.3109/10428194.2014.920503}, pmid = {24828871}, issn = {1029-2403}, mesh = {Aged ; Clostridioides difficile/*isolation &amp; purification/physiology ; Clostridium Infections/complications/microbiology/*therapy ; Drug Resistance, Bacterial ; Fecal Microbiota Transplantation/*methods ; Host-Pathogen Interactions ; Humans ; Lymphoma, B-Cell/*complications/pathology ; Male ; Neoplasm Recurrence, Local ; Recurrence ; Transplantation, Homologous ; Treatment Outcome ; }, }
@article {pmid24828361, year = {2014}, author = {Borody, TJ and Finlayson, S and Paramsothy, S}, title = {Is Crohn's disease ready for fecal microbiota transplantation?.}, journal = {Journal of clinical gastroenterology}, volume = {48}, number = {7}, pages = {582-583}, doi = {10.1097/MCG.0000000000000155}, pmid = {24828361}, issn = {1539-2031}, mesh = {Biological Therapy/*methods ; Crohn Disease/*microbiology/*therapy ; Feces/*microbiology ; Humans ; Male ; *Microbiota ; }, }
@article {pmid24825534, year = {2014}, author = {Brown, WR}, title = {Fecal microbiota transplantation in treating Clostridium difficile infection.}, journal = {Journal of digestive diseases}, volume = {15}, number = {8}, pages = {405-408}, doi = {10.1111/1751-2980.12160}, pmid = {24825534}, issn = {1751-2980}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Humans ; *Microbiota ; Patient Acceptance of Health Care ; Tissue Transplantation/adverse effects/*methods/trends ; }, abstract = {Clostridium difficile infection (CDI) is an increasingly common and severe international health problem. Customary treatment of this infection, usually with antibiotics, is often ineffective and its recurrence is common. In recent years the treatment of recurrent or refractory CDI by the transfer of stool from an uninfected person, so called fecal "microbiota transplantation" has become recognized as effective and generally safe. The effectiveness of this novel treatment is incompletely defined but is likely to be due to its correction of the intestinal dysbiosis that characterizes the disease. Practical methods for the administration of the transplantation have been described. This review summarizes the current reported experiences with fecal microbiota transplantation in the treatment for CDI.}, }
@article {pmid24820468, year = {2014}, author = {Pala, C and Kaynar, L and Buyukoglan, R and Kurnaz, F and Metan, G and Yazar, S and Durmaz, S and Sakioglu, A and Sivgin, S and Eser, B and Unal, A and Cetin, M}, title = {Diarrhea in peripheral stem cell transplant recipients: a developing country's experience.}, journal = {Journal of infection in developing countries}, volume = {8}, number = {5}, pages = {635-641}, doi = {10.3855/jidc.3602}, pmid = {24820468}, issn = {1972-2680}, mesh = {Adult ; Bacterial Infections/epidemiology/microbiology ; Developing Countries ; Diarrhea/*epidemiology/*etiology ; Female ; Humans ; Incidence ; Intestinal Diseases, Parasitic/epidemiology/parasitology ; Male ; *Peripheral Blood Stem Cell Transplantation ; Prevalence ; *Transplant Recipients ; Turkey ; Virus Diseases/epidemiology/virology ; }, abstract = {INTRODUCTION: We aimed to determine the frequency and microbiological causes of diarrhea occurring during the first 100 days in allogeneic (allo-) and autologous (auto-) stem cell transplantation (SCT) patients.<br><br>METHODOLOGY: A total of 452 patients who underwent transplantation due to hematological or solid organ malignancy were included. From the administration of the conditioning regimen up to day 100 post-transplant, diarrhea cases lasting at least three days with a minimum of three episodes per day were evaluated.<br><br>RESULTS: Cases of diarrhea were observed in 94 patients out of 227 subjects who received allo-SCT and in 107 patients out of 225 who received auto-SCT. The incidence rate of diarrhea in both patients undergoing autologous and allogeneic transplant was 47.5% and 41.4%, respectively. The cause of the diarrhea could be detected in 20.5% of auto-SCT patients and in 30.8% of allo-SCT patients. Parasitic infections were frequently observed in both autologous and allogeneic transplant patients in the first 20 days. In the late period, significantly more patients developed diarrhea in the allo-SCT recipient group than in the auto-SCT recipients due to graft versus host disease (GVHD) and cytomegalovirus (CMV) colitis.<br><br>CONCLUSIONS: This study revealed the causes of diarrhea and the prevalence and factors of parasitic infections in transplant patients in Turkey. All causative factors of diarrhea should be considered in detail, feces analyses should be evaluated for each patient, and endoscopic biopsy samples should be obtained when required in immunosuppressive patients undergoing stem cell transplantation.}, }
@article {pmid24811495, year = {2014}, author = {Ratner, M}, title = {Fecal transplantation poses dilemma for FDA.}, journal = {Nature biotechnology}, volume = {32}, number = {5}, pages = {401-402}, pmid = {24811495}, issn = {1546-1696}, mesh = {*Biological Therapy/methods/trends ; *Feces ; Humans ; United States ; United States Food and Drug Administration ; }, }
@article {pmid24810192, year = {2014}, author = {van Dam, L and Bretthauer, M}, title = {Ethical issues in colorectal cancer screening.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {28}, number = {2}, pages = {315-326}, doi = {10.1016/j.bpg.2014.03.002}, pmid = {24810192}, issn = {1532-1916}, mesh = {Colonography, Computed Tomographic ; Colorectal Neoplasms/*diagnosis/prevention &amp; control ; Early Detection of Cancer/*ethics ; Endoscopy, Gastrointestinal ; Humans ; Mass Screening/*ethics ; Occult Blood ; }, abstract = {In many countries, colorectal cancer screening is currently an established population screening program due to the evidence on its reduction of colorectal cancer mortality. There is general consensus that colorectal cancer screening meets the screening criteria as proposed by Wilson and Jungner. However, as for all population screening programs, colorectal cancer screening also has disadvantages and thereby entails ethical issues. There are the general issues concerning the introduction of screening programs (e.g. medicalization, overdiagnosis and overtreatment, information provision to screenees), evaluation of cancer screening programs (e.g. lead time and length bias), chosen screening method (e.g. false-positive and false-negative test results, reduction of all-cause mortality, choice between different screening methods). The different colorectal cancer screening methods and the ethical issues concerning colorectal cancer screening will be discussed in this review.}, }
@article {pmid24809121, year = {2014}, author = {}, title = {Solving a C.difficile problem. If antibiotics fail, a stool transplant can help cure a severe infection.}, journal = {The Johns Hopkins medical letter health after 50}, volume = {25}, number = {13}, pages = {3}, pmid = {24809121}, issn = {1042-1882}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*pathogenicity ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Humans ; Intubation, Gastrointestinal ; }, }
@article {pmid24807468, year = {2014}, author = {Mergenhagen, KA and Wojciechowski, AL and Paladino, JA}, title = {A review of the economics of treating Clostridium difficile infection.}, journal = {PharmacoEconomics}, volume = {32}, number = {7}, pages = {639-650}, pmid = {24807468}, issn = {1179-2027}, mesh = {Anti-Bacterial Agents/administration &amp; dosage/*economics/therapeutic use ; Clostridioides difficile/*drug effects ; Cost-Benefit Analysis ; Enterocolitis, Pseudomembranous/drug therapy/*economics/microbiology/*therapy ; Feces/microbiology ; *Health Care Costs ; Humans ; Microbiota ; Probiotics/administration &amp; dosage/economics/therapeutic use ; }, abstract = {Clostridium difficile infection (CDI) is a costly result of antibiotic use, responsible for an estimated 14,000 deaths annually in the USA according to the Centers for Disease Control and Prevention. Annual costs attributable to CDI are in excess of $US 1 billion. This review summarizes appropriate utilization of prevention and treatment methods for CDI that have the potential to reduce the economic and humanistic costs of the disease. Some cost-effective strategies to prevent CDI include screening and isolation of hospital admissions based on C. difficile carriage to reduce transmission in the inpatient setting, and probiotics, which are potentially efficacious in preventing CDI in the appropriate patient population. The most extensively studied agents for treatment of CDI are metronidazole, vancomycin, and fidaxomicin. Most economic comparisons between metronidazole and vancomycin favor vancomycin, especially with the emergence of metronidazole-resistant C. difficile strains. Metronidazole can only be recommended for mild disease. Moderate to severe CDI should be treated with vancomycin, preferably the compounded oral solution, which provides the most cost-effective therapeutic option. Fidaxomicin offers a clinically effective and potentially cost-effective alternative for treating moderate CDI in patients who do not have the NAP1/BI/027 strain of C. difficile. Probiotics and fecal microbiota transplant have variable efficacy and the US FDA does not currently regulate the content; the potential economic advantages of these treatment modalities are currently unknown.}, }
@article {pmid24802097, year = {2015}, author = {Komura, T and Miura, K and Shirasaka, T and Ohnuma, S and Shimada, M and Kajiwara, T and Fujishima, F and Philchenkov, A and Nakagawa, K and Kudoh, K and Haneda, S and Toshima, M and Kohyama, A and Musha, H and Naitoh, T and Shibata, C and Unno, M}, title = {Usefulness of alternate-day administration of S-1 and leucovorin in a xenograft mouse model of colorectal cancer: a shorter drug-free interval leads to more efficient antitumor effects.}, journal = {International journal of clinical oncology}, volume = {20}, number = {1}, pages = {117-125}, pmid = {24802097}, issn = {1437-7772}, mesh = {Animals ; Antimetabolites, Antineoplastic/administration &amp; dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Apoptosis/drug effects ; Cell Line, Tumor ; Colorectal Neoplasms/*drug therapy ; Drug Administration Schedule ; Drug Combinations ; Drug-Related Side Effects and Adverse Reactions/prevention &amp; control ; HT29 Cells ; Heterografts ; Humans ; Leucovorin/administration &amp; dosage/adverse effects ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Oxonic Acid/administration &amp; dosage/adverse effects ; Tegafur/administration &amp; dosage/adverse effects ; }, abstract = {BACKGROUND: A clinical trial of S-1 with leucovorin (S-1/LV) in metastatic colorectal cancer (CRC) patients demonstrated promising efficacy; however, the gastrointestinal toxicities were so severe that it has not been applied in the clinical setting. On the other hand, alternate-day administration of S-1 has been proposed to attenuate the adverse events without reducing its anticancer activity. Our present study was conducted to confirm the feasibility of alternate-day administration of S-1/LV in in vivo xenograft tumor models.<br><br>METHODS: Mice were treated with S-1/LV in a daily group (2 weeks of administration followed by 2 weeks of withdrawal) or an alternate-day group (administration on alternate days for 4 weeks), then the mice were killed and the xenograft tumors were resected. We compared body weight changes, condition of feces, mucosal injury and myelosuppression and assessed adverse reactions, tumor volume, tumor growth inhibition (TGI) and expression of Ki67, TUNEL, cIAP2 and XIAP to evaluate the antitumor activity and tumor apoptosis.<br><br>RESULTS: Severe weight loss, diarrhea, mucosal injury and myelosuppression were observed only in the daily group; however, some myelosuppression was also observed in the alternate-day group. The TGI in the alternate-day group was better than in the daily group, possibly resulting from apoptosis due to the suppression of cIAP2 but not XIAP.<br><br>CONCLUSION: Our findings suggest that alternate-day administration of S-1/LV for CRC treatment can achieve high antitumor activity without severe adverse reactions, and we propose that clinical trials with this regimen should be conducted in CRC patients.}, }
@article {pmid24797828, year = {2014}, author = {Salcedo, L and Penn, M and Damaser, M and Balog, B and Zutshi, M}, title = {Functional outcome after anal sphincter injury and treatment with mesenchymal stem cells.}, journal = {Stem cells translational medicine}, volume = {3}, number = {6}, pages = {760-767}, pmid = {24797828}, issn = {2157-6564}, mesh = {Anal Canal/injuries/metabolism/pathology/physiopathology/*surgery ; Animals ; Cells, Cultured ; Disease Models, Animal ; Female ; Fibrosis ; Green Fluorescent Proteins/biosynthesis/genetics ; Infusions, Intravenous ; Injections, Intralesional ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/metabolism ; Pressure ; Rats ; Rats, Sprague-Dawley ; Recovery of Function ; *Regeneration ; Time Factors ; Transfection ; }, abstract = {This research demonstrates the regenerative effects of mesenchymal stem cells (MSCs) on the injured anal sphincter by comparing anal sphincter pressures following intramuscular and serial intravascular MSC infusion in a rat model of anal sphincter injury. Fifty rats were divided into injury (n = 35) and no injury (NI; n = 15) groups. Each group was further divided into i.m., serial i.v., or no-treatment (n = 5) groups and followed for 5 weeks. The injury consisted of an excision of 25% of the anal sphincter complex. Twenty-four hours after injury, 5 × 10(5) green fluorescent protein-labeled MSCs in 0.2 ml of phosphate-buffered saline (PBS) or PBS alone (sham) were injected into the anal sphincter for i.m. treatment; i.v. and sham i.v. treatments were delivered daily for 6 consecutive days via the tail vein. Anal pressures were recorded before injury and 10 days and 5 weeks after treatment. Ten days after i.m. MSC treatment, resting and peak pressures were significantly increased compared with those in sham i.m. treatment (p < .001). When compared with the NI group, the injury groups had anal pressures that were not significantly different 5 weeks after i.m./i.v. treatment. Both resting and peak pressures were also significantly increased after i.m./i.v. MSC treatment compared with treatment with PBS (p < .001), suggesting recovery. Statistical analysis was done using paired t test with Bonferroni correction. Marked decrease in fibrosis and scar tissue was seen in both MSC-treated groups. Both i.m. and i.v. MSC treatment after injury caused an increase in anal pressures sustained at 5 weeks, although fewer cells were injected i.m. The MSC-treated groups showed less scarring than the PBS-treated groups, with the i.v. infusion group showing the least scarring.}, }
@article {pmid24797011, year = {2014}, author = {Swaminath, A}, title = {The power of poop: patients getting ahead of their doctors using self-administered fecal transplants.}, journal = {The American journal of gastroenterology}, volume = {109}, number = {5}, pages = {777-778}, doi = {10.1038/ajg.2014.68}, pmid = {24797011}, issn = {1572-0241}, mesh = {Adult ; Crohn Disease/*therapy ; Enema ; *Feces/microbiology ; Humans ; Male ; Self Administration ; *Transplantation ; }, }
@article {pmid24796803, year = {2014}, author = {Merenstein, D and El-Nachef, N and Lynch, SV}, title = {Fecal microbial therapy: promises and pitfalls.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {59}, number = {2}, pages = {157-161}, pmid = {24796803}, issn = {1536-4801}, support = {P01 AI089473/AI/NIAID NIH HHS/United States ; R01 AI097172/AI/NIAID NIH HHS/United States ; R21 AI113916/AI/NIAID NIH HHS/United States ; U01 HL098964/HL/NHLBI NIH HHS/United States ; }, mesh = {*Biological Therapy ; Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Dysbiosis/*therapy ; Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; }, abstract = {A rapidly expanding range of diverse human diseases is now associated with perturbations to the gastrointestinal microbiome. Fecal microbial transplant (FMT) has been used with high rates of efficacy to treat gastrointestinal microbiome perturbation associated with recurrent Clostridium difficile infection, and is now being considered for other indications. Here we discuss the gut microbiome, review published and ongoing studies using FMT as a treatment modality for human disease, consider the regulatory aspects of FMT, and outline some factors that should be considered in patients in whom this therapeutic strategy is being contemplated.}, }
@article {pmid24792627, year = {2014}, author = {Russell, GH and Kaplan, JL and Youngster, I and Baril-Dore, M and Schindelar, L and Hohmann, E and Winter, HS}, title = {Fecal transplant for recurrent Clostridium difficile infection in children with and without inflammatory bowel disease.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {58}, number = {5}, pages = {588-592}, doi = {10.1097/MPG.0000000000000283}, pmid = {24792627}, issn = {1536-4801}, mesh = {Adolescent ; Anti-Bacterial Agents/adverse effects/therapeutic use ; Child ; Child, Preschool ; *Clostridioides difficile ; Clostridium Infections/complications/*therapy ; Colonoscopy ; Feces/*microbiology ; Female ; Humans ; Infant ; Inflammatory Bowel Diseases/*complications ; Intubation, Gastrointestinal ; Male ; Microbiota/drug effects/*physiology ; Recurrence ; Transplantation/*methods ; Treatment Outcome ; Young Adult ; }, abstract = {Ten children at our institution received single-infusion fecal microbiome transplant (FMT) using healthy, related screened donor stool to treat recurrent Clostridium difficile infection (RCDI) via nasogastric tube (2 patients) or colonoscopic delivery. Nine of the 10 (90%) children had resolution of their symptoms after a single-infusion FMT with follow-up of 1 month to 4 years. No concerning related adverse events were recognized during short- or long-term follow-up. Three of these children had concomitant inflammatory bowel disease and 2 of these 3 (66%) patients cleared RCDI with no clinical change in their underlying inflammatory bowel disease clinical activity as assessed by Physician's Global Assessment. All of the patients who had clinical improvement of gastrointestinal symptoms of RCDI while treated with antibiotics had lasting return of baseline health after FMT.}, }
@article {pmid24785235, year = {2014}, author = {Dominguez, SR and Dolan, SA and West, K and Dantes, RB and Epson, E and Friedman, D and Littlehorn, CA and Arms, LE and Walton, K and Servetar, E and Frank, DN and Kotter, CV and Dowell, E and Gould, CV and Hilden, JM and Todd, JK}, title = {High colonization rate and prolonged shedding of Clostridium difficile in pediatric oncology patients.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {59}, number = {3}, pages = {401-403}, pmid = {24785235}, issn = {1537-6591}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Adolescent ; Bacterial Shedding ; Child ; Child, Preschool ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/complications/diagnosis/*epidemiology/microbiology ; Diarrhea ; Feces/microbiology ; Humans ; Infant ; Neoplasms/*complications ; Pediatrics ; Prevalence ; Young Adult ; }, abstract = {Surveillance testing for Clostridium difficile among pediatric oncology patients identified stool colonization in 29% of patients without gastrointestinal symptoms and in 55% of patients with prior C. difficile infection (CDI). A high prevalence of C. difficile colonization and diarrhea complicates the diagnosis of CDI in this population.}, }
@article {pmid24780568, year = {2014}, author = {Lankelma, JM and Nieuwdorp, M and de Vos, WM and Wiersinga, WJ}, title = {[The gut microbiota in sickness and health].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {157}, number = {}, pages = {A5901}, pmid = {24780568}, issn = {1876-8784}, mesh = {Gastrointestinal Tract/*microbiology ; Humans ; Inflammatory Bowel Diseases/immunology/microbiology ; Microbiota/*immunology/*physiology ; Obesity/immunology/microbiology ; Prebiotics ; Probiotics/administration &amp; dosage/therapeutic use ; }, abstract = {The human gut microbiota, formerly known as 'gut flora', may be regarded as an external organ with many physiological functions in metabolism, development of the immune system and defense against pathogens. The adult gut microbiota consist of 1013-1014 micro-organisms. The aggregate genome of these, known as the microbiome, is 100 times larger than the human genome. The gut microbiotica may be involved in the pathogenesis of a range of syndromes, such as inflammatory bowel disease, obesity, diabetes mellitus and atopic disorders. It should be noted that until now most of the studies conducted have been association studies, without proof of causality. This increasing insight has led to identification of new therapeutic strategies, which are currently being investigated in clinical studies. Although the implications of this knowledge for individual patients have yet to become clear, various interventions are conceivable, such as supplementation of nutritional elements, prebiotics or probiotics and feces transplantation.}, }
@article {pmid24764665, year = {2014}, author = {Wang, X and Kuang, YY and Hu, XT}, title = {Advances in epigenetic biomarker research in colorectal cancer.}, journal = {World journal of gastroenterology}, volume = {20}, number = {15}, pages = {4276-4287}, pmid = {24764665}, issn = {2219-2840}, mesh = {Biomarkers, Tumor/blood/*genetics ; Cell Line, Tumor ; Colorectal Neoplasms/blood/*genetics ; DNA Methylation ; *Epigenesis, Genetic ; Feces ; *Gene Expression Regulation, Neoplastic ; Histones/metabolism ; Humans ; MicroRNAs/metabolism ; Neoplasm Recurrence, Local/genetics ; Neoplasm Transplantation ; Prognosis ; Treatment Outcome ; }, abstract = {Colorectal cancer (CRC) causes approximately 600000 deaths annually and is the third leading cause of cancer mortality worldwide. Despite significant advancements in treatment options, CRC patient survival is still poor owing to a lack of effective tools for early diagnosis and a limited capacity for optimal therapeutic decision making. Since there exists a need to find new biomarkers to improve diagnosis of CRC, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to clinical practice. Epigenetic alterations are thought to hold great promise as tumor biomarkers. In this review, we will primarily focus on recent advances in the study of epigenetic biomarkers for colorectal cancer and discuss epigenetic biomarkers, including DNA methylation, microRNA expression and histone modification, in cancer tissue, stool, plasma, serum, cell lines and xenografts. These studies have improved the chances that epigenetic biomarkers will find a place in the clinical practices of screening, early diagnosis, prognosis, therapy choice and recurrence surveillance for CRC patients. However, these studies have typically been small in size, and evaluation at a larger scale of well-controlled randomized clinical trials is the next step that is necessary to increase the quality of epigenetic biomarkers and ensure their widespread clinical use.}, }
@article {pmid24762631, year = {2014}, author = {Youngster, I and Sauk, J and Pindar, C and Wilson, RG and Kaplan, JL and Smith, MB and Alm, EJ and Gevers, D and Russell, GH and Hohmann, EL}, title = {Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {58}, number = {11}, pages = {1515-1522}, pmid = {24762631}, issn = {1537-6591}, support = {HHSN272200900018C/AI/NIAID NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; UL1 TR000170/TR/NCATS NIH HHS/United States ; 8UL1TR000170-05/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biological Therapy/*methods ; Child ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; Colonoscopy/methods ; Diarrhea/microbiology/*therapy ; Female ; Humans ; Intubation, Gastrointestinal/methods ; Male ; Middle Aged ; Pilot Projects ; Recurrence ; Surveys and Questionnaires ; Treatment Outcome ; Unrelated Donors ; Young Adult ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (CDI) with poor response to standard antimicrobial therapy is a growing medical concern. We aimed to investigate the outcomes of fecal microbiota transplant (FMT) for relapsing CDI using a frozen suspension from unrelated donors, comparing colonoscopic and nasogastric tube (NGT) administration.<br><br>METHODS: Healthy volunteer donors were screened and a frozen fecal suspension was generated. Patients with relapsing/refractory CDI were randomized to receive an infusion of donor stools by colonoscopy or NGT. The primary endpoint was clinical resolution of diarrhea without relapse after 8 weeks. The secondary endpoint was self-reported health score using standardized questionnaires.<br><br>RESULTS: A total of 20 patients were enrolled, 10 in each treatment arm. Patients had a median of 4 (range, 2-16) relapses prior to study enrollment, with 5 (range, 3-15) antibiotic treatment failures. Resolution of diarrhea was achieved in 14 patients (70%) after a single FMT (8 of 10 in the colonoscopy group and 6 of 10 in the NGT group). Five patients were retreated, with 4 obtaining cure, resulting in an overall cure rate of 90%. Daily number of bowel movements changed from a median of 7 (interquartile range [IQR], 5-10) the day prior to FMT to 2 (IQR, 1-2) after the infusion. Self-ranked health score improved significantly, from a median of 4 (IQR, 2-6) before transplant to 8 (IQR, 5-9) after transplant. No serious or unexpected adverse events occurred.<br><br>CONCLUSIONS: In our initial feasibility study, FMT using a frozen inoculum from unrelated donors is effective in treating relapsing CDI. NGT administration appears to be as effective as colonoscopic administration.<br><br>CLINICAL TRIALS REGISTRATION: NCT01704937.}, }
@article {pmid24759832, year = {2014}, author = {Solari, PR and Fairchild, PG and Noa, LJ and Wallace, MR}, title = {Tempered enthusiasm for fecal transplant.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {59}, number = {2}, pages = {319}, doi = {10.1093/cid/ciu278}, pmid = {24759832}, issn = {1537-6591}, mesh = {Biological Therapy/*methods ; Drugs, Investigational/*therapeutic use ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; *Investigational New Drug Application ; }, }
@article {pmid24748025, year = {2014}, author = {Vaishnavi, C}, title = {Fecal microbiota transplantation for management of Clostridium difficile infection.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {33}, number = {4}, pages = {301-307}, pmid = {24748025}, issn = {0975-0711}, mesh = {Biological Therapy/*methods ; *Clostridioides difficile ; *Clostridium Infections ; Disease Management ; Enterocolitis/*microbiology/*therapy ; Feces/*microbiology ; Humans ; Intestines/microbiology ; *Microbiota ; }, abstract = {The widespread use of antibiotics has led Clostridium difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the emergence of more resistant strains of C. difficile. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Fecal microbiota transplantation (FMT) is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections. The procedure is not in regular use because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant. However, FMT is gaining popularity because of its success rate as a panacea for recurrent attacks of CDI and is being increasingly used in clinical practice. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota instillation to CDI patients in order to restore the normal gut flora.}, }
@article {pmid24742736, year = {2014}, author = {D'Haens, GR and Sartor, RB and Silverberg, MS and Petersson, J and Rutgeerts, P}, title = {Future directions in inflammatory bowel disease management.}, journal = {Journal of Crohn's &amp; colitis}, volume = {8}, number = {8}, pages = {726-734}, doi = {10.1016/j.crohns.2014.02.025}, pmid = {24742736}, issn = {1876-4479}, mesh = {Biomedical Research ; Biosimilar Pharmaceuticals/therapeutic use ; Colitis, Ulcerative/therapy ; Crohn Disease/therapy ; Forecasting ; Humans ; Inflammatory Bowel Diseases/genetics/*therapy ; }, abstract = {BACKGROUND AND AIMS: Clinical management of inflammatory bowel diseases (IBD), new treatment modalities and the potential impact of personalised medicine remain topics of intense interest as our understanding of the pathophysiology of IBD expands.<br><br>METHODS: Potential future strategies for IBD management are discussed, based on recent preclinical and clinical research.<br><br>RESULTS: A top-down approach to medical therapy is increasingly being adopted for patients with risk factors for severe inflammation or an unfavourable disease course in an attempt to halt the inflammatory process as early as possible, prevent complications and induce mucosal healing. In the future, biological therapies for IBD are likely to be used more selectively based on personalised benefit/risk assessment, determined through reliable biomarkers and tissue signatures, and will probably be optimised throughout the course of treatment. Biologics with different mechanisms of action will be available; when one drug fails, patients will be able to switch to another and even combination biologics may become a reality. The role of biotherapeutic products that are similar to currently licensed biologics in terms of quality, safety and efficacy - i.e. biosimilars - is at an early stage and requires further experience. Other therapeutic strategies may involve manipulation of the microbiome using antibiotics, probiotics, prebiotics, diet and combinations of all these approaches. Faecal microbiota transplantation is also a potential option in IBD although controlled data are lacking.<br><br>CONCLUSIONS: The future of classifying, prognosticating and managing IBD involves an outcomes-based approach to identify biomarkers reflecting various biological processes that can be matched with clinically important endpoints.}, }
@article {pmid24742697, year = {2014}, author = {Ehlermann, P and Dösch, AO and Katus, HA}, title = {Donor fecal transfer for recurrent Clostridium difficile-associated diarrhea in heart transplantation.}, journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, volume = {33}, number = {5}, pages = {551-553}, doi = {10.1016/j.healun.2014.02.002}, pmid = {24742697}, issn = {1557-3117}, mesh = {Adult ; Cardiomyopathy, Dilated/*surgery ; Clostridioides difficile/*isolation &amp; purification ; Diarrhea/*etiology/microbiology ; Enterocolitis, Pseudomembranous/*etiology/microbiology ; Feces/*microbiology ; Female ; Heart Transplantation/*adverse effects ; Humans ; }, }
@article {pmid24729930, year = {2014}, author = {Oldfield, EC and Oldfield, EC and Johnson, DA}, title = {Clinical update for the diagnosis and treatment of Clostridium difficile infection.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {5}, number = {1}, pages = {1-26}, pmid = {24729930}, issn = {2150-5349}, abstract = {Clostridium difficile infection (CDI) presents a rapidly evolving challenge in the battle against hospital-acquired infections. Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests, such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production, which will soon revolutionize the diagnostic approach to CDI. New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents, while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI. Through a comprehensive review of current medical literature, this article aims to offer an intensive review of the current state of CDI diagnosis, discuss the strengths and limitations of available laboratory tests, compare both current and future treatments options and offer recommendations for best practice strategies.}, }
@article {pmid24722168, year = {2014}, author = {Wen, K and Tin, C and Wang, H and Yang, X and Li, G and Giri-Rachman, E and Kocher, J and Bui, T and Clark-Deener, S and Yuan, L}, title = {Probiotic Lactobacillus rhamnosus GG enhanced Th1 cellular immunity but did not affect antibody responses in a human gut microbiota transplanted neonatal gnotobiotic pig model.}, journal = {PloS one}, volume = {9}, number = {4}, pages = {e94504}, pmid = {24722168}, issn = {1932-6203}, support = {R01 AT004789/AT/NCCIH NIH HHS/United States ; R01AT004789/AT/NCCIH NIH HHS/United States ; }, mesh = {Animals ; Diarrhea/immunology/*prevention &amp; control/virology ; Disease Models, Animal ; Dose-Response Relationship, Immunologic ; Gastrointestinal Tract/microbiology ; Germ-Free Life ; Humans ; Immunity, Cellular/*drug effects ; Immunity, Humoral/drug effects ; Infant ; Lacticaseibacillus rhamnosus/*immunology ; Male ; Microbiota/immunology ; Probiotics/*administration &amp; dosage ; Rotavirus/immunology ; Rotavirus Infections/immunology/*prevention &amp; control/virology ; Rotavirus Vaccines/administration &amp; dosage/*immunology ; Swine ; Th1 Cells/drug effects/immunology ; Vaccination ; }, abstract = {This study aims to establish a human gut microbiota (HGM) transplanted gnotobiotic (Gn) pig model of human rotavirus (HRV) infection and diarrhea, and to verify the dose-effects of probiotics on HRV vaccine-induced immune responses. Our previous studies using the Gn pig model found that probiotics dose-dependently regulated both T cell and B cell immune responses induced by rotavirus vaccines. We generated the HGM transplanted neonatal Gn pigs through daily feeding of neonatal human fecal suspension to germ-free pigs for 3 days starting at 12 hours after birth. We found that attenuated HRV (AttHRV) vaccination conferred similar overall protection against rotavirus diarrhea and virus shedding in Gn pigs and HGM transplanted Gn pigs. HGM promoted the development of the neonatal immune system, as evidenced by the significantly enhanced IFN-γ producing T cell responses and reduction of regulatory T cells and their cytokine production in the AttHRV-vaccinated pigs. The higher dose Lactobacillus rhamnosus GG (LGG) feeding (14 doses, up to 109 colony-forming-unit [CFU]/dose) effectively increased the LGG counts in the HGM Gn pig intestinal contents and significantly enhanced HRV-specific IFN-γ producing T cell responses to the AttHRV vaccine. Lower dose LGG (9 doses, up to 106 CFU/dose) was ineffective. Neither doses of LGG significantly improved the protection rate, HRV-specific IgA and IgG antibody titers in serum, or IgA antibody titers in intestinal contents compared to the AttHRV vaccine alone, suggesting that an even higher dose of LGG is needed to overcome the influence of the microbiota to achieve the immunostimulatory effect in the HGM pigs. This study demonstrated that HGM Gn pig is an applicable animal model for studying immune responses to rotavirus vaccines and can be used for studying interventions (i.e., probiotics and prebiotics) that may enhance the immunogenicity and protective efficacy of vaccines through improving the gut microbiota.}, }
@article {pmid24719899, year = {2014}, author = {Zipursky, JS and Sidorsky, TI and Freedman, CA and Sidorsky, MN and Kirkland, KB}, title = {Physician attitudes toward the use of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {28}, number = {6}, pages = {319-324}, pmid = {24719899}, issn = {2291-2797}, mesh = {Adult ; Aged ; Biological Therapy/*statistics &amp; numerical data ; Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Female ; Humans ; Male ; Middle Aged ; New Hampshire ; Patient Acceptance of Health Care/statistics &amp; numerical data ; Practice Patterns, Physicians'/*statistics &amp; numerical data ; Texas ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a safe and effective, yet infrequently used therapy for recurrent Clostridium difficile infection (CDI).<br><br>OBJECTIVE: To characterize barriers to FMT adoption by surveying physicians about their experiences and attitudes toward the use of FMT.<br><br>METHODS: An electronic survey was distributed to physicians to assess their experience with CDI and attitudes toward FMT.<br><br>RESULTS: A total of 139 surveys were sent and 135 were completed, yielding a response rate of 97%. Twenty-five (20%) physicians had treated a patient with FMT, 10 (8%) offered to treat with FMT, nine (7%) referred a patient to receive FMT, and 83 (65%) had neither offered nor referred a patient for FMT. Physicians who had experience with FMT (performed, offered or referred) were more likely to be male, an infectious diseases specialist, >40 years of age, fellowship trained and practicing in an urban setting. The most common reasons for not offering or referring a patient for FMT were: not having 'the right clinical situation' (33%); the belief that patients would find it too unappealing (24%); and institutional or logistical barriers (23%). Only 8% of physicians predicted that the majority of patients would opt for FMT if given the option. Physicians predicted that patients would find all aspects of the FMT process more unappealing than they would as providers.<br><br>CONCLUSIONS: Physicians have limited experience with FMT despite having treated patients with multiple recurrent CDIs. There is a clear discordance between physician beliefs about FMT and patient willingness to accept FMT as a treatment for recurrent CDI.}, }
@article {pmid24716951, year = {2014}, author = {Uysal-Sonmez, O and Tanriverdi, O and Uyeturk, U and Budakoglu, II and Kazancioglu, R and Turker, I and Budakoglu, B and Yalcintas-Arslan, U and Oksuzoglu, B}, title = {Awareness of cancer screening during treatment of patients with renal failure: a physician survey in Turkey.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {5}, pages = {2165-2168}, doi = {10.7314/apjcp.2014.15.5.2165}, pmid = {24716951}, issn = {2476-762X}, mesh = {Adult ; Breast Self-Examination/statistics &amp; numerical data ; Data Collection/statistics &amp; numerical data ; Early Detection of Cancer/*statistics &amp; numerical data ; Female ; Humans ; Male ; Mammography/statistics &amp; numerical data ; Middle Aged ; Neoplasms/*diagnosis ; Physical Examination/statistics &amp; numerical data ; Physicians/statistics &amp; numerical data ; Practice Patterns, Physicians'/*statistics &amp; numerical data ; Renal Insufficiency/*therapy ; Surveys and Questionnaires ; Turkey ; }, abstract = {BACKGROUND: Today, survival rate of patients with chronic renal failure/hemodialysis has increased so that chronic illnesses are more likely to occur. Cancer is the main cause of morbidity and mortality in such patients.<br><br>AIM: In this study, physician attitudes were examined about cancer screening in patients with renal failure.<br><br>MATERIALS AND METHODS: This study was done by face to face questionnaire in the 27th National Nephrology Congress to determine if the physicians dealing with chronic renal failure, hemodialysis or renal transplanted patients, recommend cancer screening or not and the methods of screening for cervix, prostate, breast and colon cancer.<br><br>RESULTS: One hundred and fifty six physicians were included in the survey. A total of 105 (67%) participants were male and the age of responders was 48 &#xb1; 9 years. About 29% were specialists in nephrology, 28% internal medicine, and 5% were other areas of expertise. Some 48% of participants were hemodialysis certified general practitioners. Patients were grouped as compensated chronic renal failure, hemodialysis or renal transplanted. Of the 156 responders, 128 (82%) physicians recommended breast cancer screening and the most recommended subgroup was hemodialysis patients (15%). The most preferred methods of screening were combinations of mammography, self breast examination and physician breast examination. 112 (72%) physicians recommended cervix cancer screening, and the most preferred method of screening was pap-smear. Colon cancer screening was recommended by 102 (65%) physicians and prostate screening by 109 (70%) physicians. The most preferred methods of screening were fecal occult blood test and PSA plus rectal digital test, respectively.<br><br>CONCLUSIONS: It is not obvious whether cancer screening in renal failure patients is different from the rest of society. There is a variety of screening methods. An answer can be found to these questions as a result of studies by a common follow-up protocol and cooperation of nephrologists and oncologists.}, }
@article {pmid24707129, year = {2014}, author = {Allegretti, JR and Hamilton, MJ}, title = {Restoring the gut microbiome for the treatment of inflammatory bowel diseases.}, journal = {World journal of gastroenterology}, volume = {20}, number = {13}, pages = {3468-3474}, pmid = {24707129}, issn = {2219-2840}, support = {K08 DK094971/DK/NIDDK NIH HHS/United States ; T32 DK007533/DK/NIDDK NIH HHS/United States ; }, mesh = {Biological Therapy/methods ; Clostridioides difficile ; Clostridium Infections/microbiology ; Colitis, Ulcerative/microbiology ; Crohn Disease/microbiology ; Dysbiosis/immunology ; Feces/*microbiology ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Intestines/*microbiology ; *Microbiota ; Pouchitis/immunology ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is considered to be a highly successful therapy for recurrent and refractory Clostridium difficile infection (CDI) based on recent clinical trials. The pathogenesis of inflammatory bowel diseases (IBD) is thought to be due in part to perturbations in the gut microflora that disrupt homeostasis. FMT restores essential components of the microflora which could reverse the inflammatory processes observed in IBD. Case reports and series for the treatment of IBD by FMT have shown promise with regards to treatment success and safety despite the limitations of the reporting. Future studies will determine the optimal delivery and preparation of stool as well as the conditions under which the recipient will derive maximal benefit. The long term consequences of FMT with regards to infection, cancer, auto-immune, and metabolic diseases are not known and will require continued regulation and study. Despite these limitations, FMT may be beneficial for the treatment of ulcerative colitis and Crohn's disease, particularly those with concurrent CDI or with pouchitis.}, }
@article {pmid24703718, year = {2014}, author = {An, L and Hu, H and Du, J and Wei, J and Wang, L and Yang, H and Wu, D and Shi, H and Li, F and Yang, S}, title = {Paramagnetic hollow silica nanospheres for in vivo targeted ultrasound and magnetic resonance imaging.}, journal = {Biomaterials}, volume = {35}, number = {20}, pages = {5381-5392}, doi = {10.1016/j.biomaterials.2014.03.030}, pmid = {24703718}, issn = {1878-5905}, mesh = {Administration, Intravenous ; Animals ; Cell Line, Tumor ; Contrast Media ; Disease Models, Animal ; Drug Delivery Systems ; Feces/chemistry ; Gadolinium DTPA/chemistry/pharmacokinetics ; Humans ; Liver/metabolism ; Lung/metabolism ; Magnetic Resonance Imaging/*methods ; Male ; Mice ; Mice, Nude ; Nanospheres/*chemistry ; Neoplasm Transplantation ; Neoplasms/*diagnostic imaging ; Oligopeptides/chemistry/pharmacokinetics ; Polystyrenes/chemistry ; Silicon Dioxide/*chemistry/pharmacokinetics ; Tissue Distribution ; Ultrasonography ; }, abstract = {A series of hollow silica nanospheres (HSNSs) with sizes ranging from 100 to 400 nm were synthesized and used for primary ultrasound imaging (US) efficiency assessment. The 400 nm HSNSs were chosen as platform for conjugation with Gd-DTPA and cyclo-arginine-glycine-aspartic acid c(RGD) peptide to construct US and magnetic resonance imaging (MRI) dual-modal contrast agents (CAs): [HSNSs@(DTPA-Gd)-RGD]. The obtained CAs displayed good physiological stability, low cytotoxicity and negligible hemolytic activity in vitro. Furthermore, the passive accumulation and active-targeting of the HSNSs in the tumor site of mice was demonstrated by US and MR imaging, respectively. The qualitative and quantitative biodistribution of the HSNSs showed that they mainly accumulated in the tissues of liver, lung, tumor after intravenous administration and then be excreted from feces. In addition, histological, hematological, blood and biochemical analysis were used to further study toxicity of the HSNSs, and all results indicated that there were no covert toxicity of HSNSs in mice after long exposure times. Findings from this study indicated that the silica-based paramagnetic HSNSs can be used as a platform for long-term targeted imaging and therapy studies safely in vivo.}, }
@article {pmid24692533, year = {2014}, author = {Konijeti, GG and Sauk, J and Shrime, MG and Gupta, M and Ananthakrishnan, AN}, title = {Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {58}, number = {11}, pages = {1507-1514}, pmid = {24692533}, issn = {1537-6591}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; T32 DK007191/DK/NIDDK NIH HHS/United States ; T32DK007191/DK/NIDDK NIH HHS/United States ; K23 DK091742/DK/NIDDK NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*economics/*therapeutic use ; Biological Therapy/*economics/*methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*prevention &amp; control/*therapy ; Cost-Benefit Analysis ; Decision Support Techniques ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI.<br><br>METHODS: We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year.<br><br>RESULTS: At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin.<br><br>CONCLUSIONS: In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI.}, }
@article {pmid24691086, year = {2014}, author = {Rabe, SM}, title = {Treatment of recurrent Clostridium difficile infection with fecal transplantation.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {37}, number = {2}, pages = {156-63; quiz 164-5}, doi = {10.1097/SGA.0000000000000035}, pmid = {24691086}, issn = {1538-9766}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Feces ; Humans ; Intestines/microbiology ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridium difficile infection is an increasingly common clinical challenge in hospitals and healthcare facilities. The infection often results in severe complications for the infected individual including relentless diarrhea, abdominal pain, dehydration, and mortality. Currently, there is a significant gap between research and practice in the management of recurrent Clostridium difficile infection, and treatment guidelines are limited. Numerous attempts at treating this infection have been made including the practice of fecal transplantation. A comprehensive literature search was conducted and 6 studies were reviewed to evaluate the safety and effectiveness of fecal transplantation as a modality in treating recurrent Clostridium difficile infection refractory to other treatment methodologies. The implementation of fecal transplantation is suggested to restore normal bowel flora in individuals with Clostridium difficile and rid patients of the infection. Additional studies have since revealed perceived barriers toward the implementation of this treatment modality, although it has shown promising results with success rates of 83%-100%. Further efficacy testing validation is needed in larger, prospective controlled trials to guide healthcare providers in the direction of a reliable, standardized treatment protocol for recurrent Clostridium difficile infection.}, }
@article {pmid24691073, year = {2014}, author = {Tyakht, AV and Alexeev, DG and Popenko, AS and Kostryukova, ES and Govorun, VM}, title = {Rural and urban microbiota: To be or not to be?.}, journal = {Gut microbes}, volume = {5}, number = {3}, pages = {351-356}, pmid = {24691073}, issn = {1949-0984}, mesh = {*Biota ; Cohort Studies ; Gastrointestinal Tract/*microbiology ; Humans ; Metagenomics ; *Microbiota ; Rural Population ; Russia ; Urban Population ; }, abstract = {A multitude of metagenomic studies has brought to light an enormous richness of human gut microbiota compositions. In this space of possible configurations, clinical specialists are trying to mine the markers of healthy microbiota via case-control and longitudinal studies. We have discovered potentially beneficial communities while examining the microbial diversity in rural Russians in comparison with the urban dwellers. In this addendum, we further examine the data by elaborating on some of the less common types and suggesting the possible co-metabolism of their drivers. In the light of the first validated clinically effective bacterial transplantation, we discuss the concept of a reference healthy microbiota, outline the problems encountered on the way to its restoration in the developed world, and speculate if rural communities can serve as a source for its prototype.}, }
@article {pmid24690456, year = {2014}, author = {Hu, C and Sunday, R and Bruminhent, J and Bobik, B and Wagner, J and Weiss, M and Flomenberg, P and Wang, ZX}, title = {Investigation of a Clostridium difficile cluster by multilocus sequence typing in a bone marrow transplant unit.}, journal = {American journal of infection control}, volume = {42}, number = {6}, pages = {691-693}, doi = {10.1016/j.ajic.2014.02.008}, pmid = {24690456}, issn = {1527-3296}, mesh = {Adult ; Bacterial Typing Techniques ; Bone Marrow Transplantation ; Carrier State/microbiology ; Clostridioides difficile/*classification/genetics ; Disease Outbreaks ; Enterocolitis, Pseudomembranous/*epidemiology/*microbiology ; Feces/microbiology ; Humans ; Middle Aged ; Multilocus Sequence Typing ; }, }
@article {pmid24685366, year = {2014}, author = {Pareja-Sierra, T}, title = {[Diarrhea associated with Clostridium difficile in the elderly: new perspectives].}, journal = {Revista espanola de geriatria y gerontologia}, volume = {49}, number = {4}, pages = {188-193}, doi = {10.1016/j.regg.2014.02.006}, pmid = {24685366}, issn = {1578-1747}, mesh = {Aged ; *Clostridioides difficile ; Clostridium Infections/*complications/diagnosis/epidemiology/therapy ; Diarrhea/*microbiology ; Humans ; Risk Factors ; }, abstract = {Infection due to Clostridium difficile is currently the main cause of hospital acquired gastrointestinal disease. Its prevalence in the elderly population is higher due to there being many associated risk factors in this age group, such as comorbidity, frequent exposure to the healthcare or residential home setting, immunosenescence, greater consumption of antibiotics, and antiacids. The diagnostic techniques have notably improved in the last few years, which could also account for an increase in its diagnosis. The new expert consensus recommendations propose stratifying the clinical situation of the patient in order to choose the treatment option. Therapeutic options have recently been included in the new Clinical Guidelines, such as flidaxomicin or fecal transplants, with encouraging results, particularly for the control of frequent recurrences.}, }
@article {pmid24684485, year = {2014}, author = {Goldenberg, SU and Erzini, K}, title = {Seagrass feeding choices and digestive strategies of the herbivorous fish Sarpa salpa.}, journal = {Journal of fish biology}, volume = {84}, number = {5}, pages = {1474-1489}, doi = {10.1111/jfb.12371}, pmid = {24684485}, issn = {1095-8649}, mesh = {Animals ; Diet/*veterinary ; Feces/chemistry ; *Gastrointestinal Transit ; *Herbivory ; Nutritive Value ; Perciformes/*physiology ; Portugal ; *Zosteraceae/chemistry ; }, abstract = {This is the first study investigating the plant-herbivore interaction between Sarpa salpa, which has overgrazed seagrass transplants in Portugal, and the seagrasses Cymodocea nodosa, Zostera marina and Zostera noltii, which have been considered for restoration. When offered the choice between the three seagrasses in outdoor tanks, adult S. salpa clearly preferred Z. noltii. Testing the seagrasses separately, mean ± s.d. feeding rates ranged from 21 ± 11 g seagrass fresh mass kg[-1] fish mass day[-1] for Z. marina to 32 ± 9 g seagrass fresh mass kg[-1] fish mass day[-1] for C. nodosa and 40 ± 11 g seagrass fresh mass kg[-1] fish mass day[-1] for Z. noltii (temperature = 16° C). Food-processing rate in S. salpa did not differ between seagrasses, and there was no evidence of a regulation of processing rate according to food intake. Seagrasses differed substantially in nitrogen content and C:N, with C. nodosa containing the highest nitrogen content and lowest C:N (2·5 ± 0·1% and 14·0 ± 1·0), followed by Z. noltii (2·1 ± 0·1% and 17·0 ± 1·0) and Z. marina (1·4 ± 0·1% and 26·0 ± 2·0). Food-processing rate in S. salpa and the nutritional value of the seagrasses were not correlated with the observed feeding preference and rate. The study suggests that C. nodosa and Z. marina are less at risk of overgrazing by S. salpa and might thus be preferable to Z. noltii for seagrass restoration in areas with noticeable abundances of this fish.}, }
@article {pmid24681100, year = {2014}, author = {Walsh, CJ and Guinane, CM and O'Toole, PW and Cotter, PD}, title = {Beneficial modulation of the gut microbiota.}, journal = {FEBS letters}, volume = {588}, number = {22}, pages = {4120-4130}, doi = {10.1016/j.febslet.2014.03.035}, pmid = {24681100}, issn = {1873-3468}, mesh = {Animals ; Anti-Infective Agents/pharmacology/therapeutic use ; Feces/microbiology ; Gastrointestinal Diseases/diet therapy/drug therapy/microbiology ; Gastrointestinal Tract/drug effects/*microbiology ; Humans ; *Microbiota/drug effects ; Probiotics/pharmacology/therapeutic use ; }, abstract = {The human gut microbiota comprises approximately 100 trillion microbial cells and has a significant effect on many aspects of human physiology including metabolism, nutrient absorption and immune function. Disruption of this population has been implicated in many conditions and diseases, including examples such as obesity, inflammatory bowel disease and colorectal cancer that are highlighted in this review. A logical extension of these observations suggests that the manipulation of the gut microbiota can be employed to prevent or treat these conditions. Thus, here we highlight a variety of options, including the use of changes in diet (including the use of prebiotics), antimicrobial-based intervention, probiotics and faecal microbiota transplantation, and discuss their relative merits with respect to modulating the intestinal community in a beneficial way.}, }
@article {pmid24674093, year = {2014}, author = {Seol, CA and Park, JS and Sung, H and Kim, MN}, title = {Co-colonization of vanA and vanB Enterococcus faecium of clonal complex 17 in a patient with bacteremia due to vanA E. faecium.}, journal = {Diagnostic microbiology and infectious disease}, volume = {79}, number = {2}, pages = {141-143}, doi = {10.1016/j.diagmicrobio.2014.02.018}, pmid = {24674093}, issn = {1879-0070}, mesh = {Asian People ; Bacteremia/*microbiology ; Bacterial Proteins/*genetics ; Carbon-Oxygen Ligases/*genetics ; Electrophoresis, Gel, Pulsed-Field ; Enterococcus faecium/classification/*genetics/*isolation &amp; purification ; Feces/microbiology ; Genotype ; Gram-Positive Bacterial Infections/*microbiology ; Humans ; Male ; Middle Aged ; Molecular Typing ; Republic of Korea ; *Vancomycin Resistance ; }, abstract = {A 53-year-old Vietnamese man with liver cirrhosis was transferred from a Vietnamese hospital to our tertiary care hospital in Korea in order to undergo a liver transplantation. Bacteremia due to vanA Enterococcus faecium was diagnosed, and stool surveillance cultures for vancomycin-resistant enterococci (VRE) were positive for both vanA and vanB E. faecium. Pulsed-field gel electrophoresis analysis revealed that the 2 vanA VRE isolates from the blood and stool were clonal, but the vanB VRE was unrelated to the vanA VRE. vanA and vanB VRE were ST64 and ST18, single-allele variations of clonal complex 17, respectively. This is the first case report of vanA VRE bacteremia in a Vietnamese patient and demonstrates the reemergence of vanB VRE since a single outbreak occurred 15years ago in Korea. The reemergence of vanB VRE emphasizes the importance of VRE genotyping to prevent the spread of new VRE strains.}, }
@article {pmid24667590, year = {2014}, author = {Kao, D and Hotte, N and Gillevet, P and Madsen, K}, title = {Fecal microbiota transplantation inducing remission in Crohn's colitis and the associated changes in fecal microbial profile.}, journal = {Journal of clinical gastroenterology}, volume = {48}, number = {7}, pages = {625-628}, doi = {10.1097/MCG.0000000000000131}, pmid = {24667590}, issn = {1539-2031}, mesh = {Adult ; Biological Therapy/*methods ; Crohn Disease/*microbiology/*therapy ; Feces/*microbiology ; Humans ; Male ; *Microbiota ; RNA, Ribosomal, 16S/analysis ; Remission Induction ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine of unclear etiology. Increasing evidence has pointed to intestinal dysbiosis as a potential factor in a genetically susceptible individual. Fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease with variable degrees of success. Herein, we report a patient with Crohn's colitis, previously failing an immunosuppressant, who achieved clinical, endoscopic, and histologic remission after a single fecal microbiota transplantation infusion. We have further characterized the changes in the fecal microbiota associated with this observation.}, }
@article {pmid24664520, year = {2014}, author = {Cammarota, G and Ianiro, G and Bibbò, S and Gasbarrini, A}, title = {Gut microbiota modulation: probiotics, antibiotics or fecal microbiota transplantation?.}, journal = {Internal and emergency medicine}, volume = {9}, number = {4}, pages = {365-373}, pmid = {24664520}, issn = {1970-9366}, mesh = {*Anti-Bacterial Agents/pharmacology ; Feces/*microbiology ; Humans ; Intestines/*microbiology ; *Microbiota/drug effects ; *Probiotics ; }, abstract = {Gut microbiota is known to have a relevant role in our health, and is also related to both gastrointestinal and extradigestive diseases. Therefore, restoring the alteration of gut microbiota represents an outstanding clinical target for the treatment of gut microbiota-related diseases. The modulation of gut microbiota is perhaps an ancestral, innate concept for human beings. At this time, the restoration of gut microbiota impairment is a well-established concept in mainstream medicine, and several therapeutic approaches have been developed in this regard. Antibiotics, prebiotics and probiotics are the best known and commercially available options to overcome gastrointestinal dysbiosis. Fecal microbiota transplantation is an old procedure that has recently become popular again. It has shown a clear effectiveness in the treatment of C. difficile infection, and now represents a cutting-edge option for the restoration of gut microbiota. Nevertheless, such weapons should be used with caution. Antibiotics can indeed harm and alter gut microbiota composition. Probiotics, instead, are not at all the same thing, and thinking in terms of different strains is probably the only way to improve clinical outcomes. Moreover, fecal microbiota transplantation has shown promising results, but stronger proofs are needed. Considerable efforts are needed to increase our knowledge in the field of gut microbiota, especially with regard to the future use in its modulation for therapeutic purposes.}, }
@article {pmid24662889, year = {2014}, author = {Kinnebrew, MA and Lee, YJ and Jenq, RR and Lipuma, L and Littmann, ER and Gobourne, A and No, D and van den Brink, M and Pamer, EG and Taur, Y}, title = {Early Clostridium difficile infection during allogeneic hematopoietic stem cell transplantation.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e90158}, pmid = {24662889}, issn = {1932-6203}, support = {1R01 AI42135/AI/NIAID NIH HHS/United States ; R01 HL069929/HL/NHLBI NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; K23 AI095398/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; T32GM07739/GM/NIGMS NIH HHS/United States ; 1K23 AI095398-01/AI/NIAID NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; T32 GM007739/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Clostridioides difficile/*physiology ; Clostridium Infections/*etiology ; Cohort Studies ; Endpoint Determination ; Feces/microbiology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Intestines/microbiology ; Male ; Middle Aged ; Transplantation, Homologous/adverse effects ; Young Adult ; }, abstract = {Clostridium difficile infection (CDI) is frequently diagnosed in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We characterized early-transplant CDI and its associations, and analyzed serially-collected feces to determine intestinal carriage of toxigenic C. difficile. Fecal specimens were collected longitudinally from 94 patients during allo-HSCT hospitalization, from the start of pre-transplant conditioning until up to 35 days after stem cell infusion. Presence of C. difficile 16S rRNA and tcdB genes was determined. Clinical variables and specimen data were analyzed for association with development of CDI. Historical data from an additional 1144 allo-HSCT patients was also used. Fecal specimens from 37 patients (39%) were found to harbor C. difficile. Early-transplant CDI was diagnosed in 16 of 94 (17%) patients undergoing allo-HSCT; cases were generally mild and resembled non-CDI diarrhea associated with transplant conditioning. CDI was associated with preceding colonization with tcdB-positive C. difficile and conditioning regimen intensity. We found no associations between early-transplant CDI and graft-versus-host disease or CDI later in transplant. CDI occurs with high frequency during the early phase of allo-HSCT, where recipients are pre-colonized with toxigenic C. difficile. During this time, CDI incidence peaks during pre-transplant conditioning, and is correlated to intensity of the treatment. In this unique setting, high rates of CDI may be explained by prior colonization and chemotherapy; however, cases were generally mild and resembled non-infectious diarrhea due to conditioning, raising concerns of misdiagnosis. Further study of this unique population with more discriminating CDI diagnostic tests are warranted.}, }
@article {pmid24651084, year = {2014}, author = {Russello, G and Brovarone, F and Bardaro, M and Carretto, E}, title = {[Treating Clostridium difficile infection with faecal transplantation: donor microbiological testing].}, journal = {Le infezioni in medicina}, volume = {22}, number = {1}, pages = {5-10}, pmid = {24651084}, issn = {2532-8689}, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; *Feces/microbiology ; Humans ; *Microbiota ; }, abstract = {Clostridium difficile associated diseases (CDADs) or C. difficile infections (CDIs) are increasing in incidence, severity and mortality. Among patients with CDIs, those with recurrent disease are less responsive to traditional therapies with commonly used drugs, such as metronidazole and vancomycin. Faecal microbiota transplantation is an old therapeutic procedure that has been recently proposed as a safe and effective treatment for CDI patients non-responsive to antibiotic therapy. In this paper we discuss the microbiological procedures that should be performed on faecal microbiota donors.}, }
@article {pmid24641826, year = {2014}, author = {August, KJ and Chiang, KY and Qayed, M and Dulson, A and Worthington-White, D and Cole, CR and Horan, JT}, title = {Relative defects in mucosal immunity predict acute graft-versus-host disease.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {20}, number = {7}, pages = {1056-1059}, doi = {10.1016/j.bbmt.2014.03.012}, pmid = {24641826}, issn = {1523-6536}, mesh = {Acute Disease ; Adolescent ; Child ; Child, Preschool ; Female ; Graft vs Host Disease/*immunology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunity, Mucosal ; Infant ; Male ; Transplantation, Homologous ; Young Adult ; }, abstract = {Impairment of gut mucosal immunity by the transplant process could facilitate translocation of commensal bacteria and thereby augment the graft-versus-host response. To begin to assess the influence of gut mucosal immunity on the development of acute graft-versus-host disease (GVHD), we conducted a prospective study in 24 pediatric allogeneic hematopoietic cell transplant recipients, assessing 4 fecal markers of mucosal immunity: calprotectin, soluble CD8 (sCD8), soluble intracellular adhesion molecule 1, and β-defensin-2. Stool samples were collected prospectively on transplant days 0, +5, +10, and +15 and analyzed by ELISA. Lower levels on day +5 (calprotectin and β-defensin-2) and day +10 (calprotectin, β-defensin-2, and sCD8) were associated with subsequent acute GVHD. The most striking difference was with calprotectin on day +10. Patients with levels below 424 mg/kg had an incidence of 77.8%, whereas those with levels above this threshold had a cumulative incidence of 0% (P = .002). Relative defects in gut mucosal immunity may be important in the pathogenesis of acute GVHD.}, }
@article {pmid24641570, year = {2014}, author = {Sha, S and Liang, J and Chen, M and Xu, B and Liang, C and Wei, N and Wu, K}, title = {Systematic review: faecal microbiota transplantation therapy for digestive and nondigestive disorders in adults and children.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {39}, number = {10}, pages = {1003-1032}, doi = {10.1111/apt.12699}, pmid = {24641570}, issn = {1365-2036}, mesh = {Adult ; Child ; Clostridium Infections/therapy ; Colitis, Ulcerative/therapy ; Fatigue Syndrome, Chronic/therapy ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; Inflammatory Bowel Diseases/*therapy ; Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: There has been growing interest in the use of faecal microbiota transplantation (FMT) for the treatment of gastrointestinal and nongastrointestinal diseases.<br><br>AIM: To review systematically the reported efficacy and safety of FMT in the management of gastrointestinal and nongastrointestinal disorders in adults and children.<br><br>METHODS: The systematic review followed Cochrane and PRISMA recommendations. Available articles were identified using three electronic databases in addition to hand searching and contacting experts. Inclusion criteria were any reports of FMT therapy written in English.<br><br>RESULTS: A total of 844 patients who had undergone FMT were identified from 67 published studies. The most common indications were refractory/relapsing Clostridium difficile infection (CDI) (76.3%) and inflammatory bowel disease (IBD) (13.2%). There has been only one placebo-controlled trial, a successful trial in 43 patients with recurrent CDI. Seven publications report FMT in paediatric patients with a total of 11 treated, 3 with chronic constipation and the remainder with recurrent CDI or ulcerative colitis (UC). 90.7% of patients with refractory/relapsing CDI were cured and 78.4% of patients with IBD were in remission after FMT. FMT therapy could also be effective in treatment of some nongastrointestinal disorders such as chronic fatigue syndrome. The only reported serious adverse event attributed to the therapy was a case of suspected peritonitis.<br><br>CONCLUSIONS: Although more controlled trials are needed, faecal microbiota transplantation therapy shows promise in both adults and children with gastrointestinal diseases such as CDI and IBD.}, }
@article {pmid24637796, year = {2014}, author = {Hintze, KJ and Cox, JE and Rompato, G and Benninghoff, AD and Ward, RE and Broadbent, J and Lefevre, M}, title = {Broad scope method for creating humanized animal models for animal health and disease research through antibiotic treatment and human fecal transfer.}, journal = {Gut microbes}, volume = {5}, number = {2}, pages = {183-191}, pmid = {24637796}, issn = {1949-0984}, mesh = {Animals ; Anti-Bacterial Agents ; Feces/microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Mice ; Models, Animal ; }, abstract = {Traditionally, mouse humanization studies have used human fecal transfer to germ-free animals. This practice requires gnotobiotic facilities and is restricted to gnotobiotic mouse lines, which limits humanized mouse research. We have developed a generalizable method to humanize non germ-free mice using antibiotic treatment and human fecal transfer. The method involves depleting resident intestinal microbiota with broad-spectrum antibiotics, introducing human microbiota from frozen fecal samples by weekly gavage, and maintaining mice in HEPA-filtered microisolator cages. Pyrosequencing cecal microbiota 16S rRNA genes showed that recipient mice adopt a humanized microbiota profile analogous to their human donors, and distinct from mice treated with only antibiotics (no fecal transfer) or untreated control mice. In the humanized mice, 75% of the sequence mass was observed in their respective human donor and conversely, 68% of the donor sequence mass was recovered in the recipient mice. Principal component analyses of GC- and HPLC-separated cecal metabolites were performed to determine effects of transplanted microbiota on the metabolome. Cecal metabolite profiles of mice treated with only antibiotics (no fecal transfer) and control mice were dissimilar from each other and from humanized mice. Metabolite profiles for mice humanized from different donor samples clustered near each other, yet were sufficiently distinct that separate clusters were apparent for each donor. Also, cecal concentrations of 57 metabolites were significantly different between humanization treatments. These data demonstrate that our protocol can be used to humanize non germ-free mice and is sufficiently robust to generate metabolomic differences between mice humanized from different human donors.}, }
@article {pmid24636428, year = {2014}, author = {McCune, VL and Struthers, JK and Hawkey, PM}, title = {Faecal transplantation for the treatment of Clostridium difficile infection: a review.}, journal = {International journal of antimicrobial agents}, volume = {43}, number = {3}, pages = {201-206}, doi = {10.1016/j.ijantimicag.2013.10.009}, pmid = {24636428}, issn = {1872-7913}, mesh = {Biological Therapy/adverse effects/*methods ; Clinical Trials as Topic ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Gastroenteritis/microbiology/*therapy ; Humans ; Treatment Outcome ; }, abstract = {Clostridium difficile infection (CDI) remains a major healthcare burden despite recent global falls in its prevalence. The risk of recurrence is high when using antibiotics such as vancomycin, particularly in already recurrent disease. In light of this, new therapy options are being perused, including novel antibiotics such as fidaxomicin, probiotics, intravenous immunoglobulin and faecal transplantation. Faecal transplantation, referred to here as human probiotic infusion (HPI), is attracting an increasing amount of interest from physicians and patients. Its use has been documented in ca. 500 cases for the treatment of CDI, with overall efficacy rates reported to be ca. 91%. The first randomised controlled trial (RCT) demonstrated that HPI was superior to a 14-day course of vancomycin (89% vs. 31%; P<0.001) and reported no deaths or serious adverse events. Safety and patient acceptability are often cited as limitations to the widespread use of this technique. However, data suggest that the short-term safety profile is encouraging, and concerns over patient acceptability are not warranted in the majority of cases. It seems appropriate to treat an infection which is caused by a major disturbance in the gut microbiota with a treatment that reverses this disturbance, rather than antibiotics that may exacerbate the problem. However, to fully understand the role of HPI in the management of CDI, further RCTs are needed with comparator antibiotics such as fidaxomicin and to establish the most efficacious HPI protocol for administration and preparation.}, }
@article {pmid24629316, year = {2013}, author = {Hallundbæk Mikkelsen, K and Nielsen, MF and Tvede, M and Hansen, T and Pedersen, OB and Holst, JJ and Vilsbøll, T and Knop, FK}, title = {[Gut microbiota may have influence on glucose and lipid metabolism].}, journal = {Ugeskrift for laeger}, volume = {175}, number = {46}, pages = {2785-2788}, pmid = {24629316}, issn = {1603-6824}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/classification/genetics/*metabolism ; Blood Glucose/*metabolism ; Diabetes Mellitus, Type 2/metabolism/microbiology ; Humans ; Intestinal Mucosa/metabolism ; Intestines/*microbiology ; *Lipid Metabolism ; *Microbiota ; Obesity/metabolism/microbiology ; }, abstract = {New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gut microbiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gut microbiota and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism.}, }
@article {pmid24627239, year = {2014}, author = {Lee, CH and Belanger, JE and Kassam, Z and Smieja, M and Higgins, D and Broukhanski, G and Kim, PT}, title = {The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {33}, number = {8}, pages = {1425-1428}, pmid = {24627239}, issn = {1435-4373}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Clostridioides difficile/*drug effects ; Clostridium Infections/microbiology/*therapy ; Cross Infection/microbiology/*therapy ; Drug Resistance, Bacterial ; Enema ; Feces/microbiology ; Female ; Follow-Up Studies ; Humans ; Male ; *Microbiota ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {Clostridium difficile infection (CDI) is one of the most frequent causes of healthcare-associated infections, and its rates are also increasing in the community. The management of CDI has become a major challenge, given growing rates of recurrences and failures with standard antibiotic therapy. Mounting evidence suggests that fecal microbiota transplantation (FMT) may be effective; however, as there is a paucity of data with regard to repeat FMT for primary non-response to this treatment, this study examined the outcome of multiple FMTs for recurrent CDI. Case records were reviewed for 94 patients who underwent FMT via retention enema for recurrent or refractory CDI during the period 2008-2012. Demographic information, treatment data, and clinical resolution rates were examined for single FMT and cumulative resolution was assessed for multiple FMTs in the context of ongoing symptoms. The cumulative clinical resolution following four or more FMTs was 86%. When antibiotic therapy was used between FMTs, the clinical resolution rate increased to 92%. There were no reported adverse events and no patients who were cured with FMT had further episodes of CDI at 6-24 months follow-up. Multiple FMTs administered through enemas is an effective, safe, and simple therapy for the management of recurrent or refractory CDI.}, }
@article {pmid24612332, year = {2014}, author = {Wang, ZK and Yang, YS and Stefka, AT and Sun, G and Peng, LH}, title = {Review article: fungal microbiota and digestive diseases.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {39}, number = {8}, pages = {751-766}, doi = {10.1111/apt.12665}, pmid = {24612332}, issn = {1365-2036}, mesh = {Bacteria/isolation &amp; purification ; Feces/microbiology ; Fungi/isolation &amp; purification ; Gastrointestinal Diseases/*microbiology/physiopathology ; Humans ; Inflammation/*microbiology/physiopathology ; Inflammatory Bowel Diseases/*microbiology/physiopathology ; Microbiota ; }, abstract = {BACKGROUND: The role of the fungal microbiota in digestive diseases is poorly defined, but is becoming better understood due to advances in metagenomics.<br><br>AIM: To review the gastrointestinal fungal microbiota and its relationship with digestive diseases.<br><br>METHODS: Search of the literature using PubMed and MEDLINE databases. Subject headings including 'fungal-bacterial interactions', 'mycotoxins', 'immunity to fungi', 'fungal infection', 'fungal microbiota', 'mycobiome' and 'digestive diseases' were used.<br><br>RESULTS: The fungal microbiota is an integral part of the gastrointestinal microecosystem with up to 10(6) microorganisms per gram of faeces. Next-generation sequencing of the fungal 18S rRNA gene has allowed better characterisation of the gastrointestinal mycobiome. Numerous interactions between fungi and bacteria and the complex immune response to gastrointestinal commensal or pathogenic fungi all impact on the pathophysiology of inflammatory bowel disease and other gastrointestinal inflammatory entities such as peptic ulcers. Mycotoxins generated as fungal metabolites contribute to disturbances of gastrointestinal barrier and immune functions and are associated with chronic intestinal inflammatory conditions as well as hepatocellular and oesophagogastric cancer. Systemic and gastrointestinal disease can also lead to secondary fungal infections. Fungal genomic databases and methodologies need to be further developed and will allow a much better understanding of the diversity and function of the mycobiome in gastrointestinal inflammation, tumourigenesis, liver cirrhosis and transplantation, and its alteration as a consequence of antibiotic therapy and chemotherapy.<br><br>CONCLUSIONS: The fungal microbiota and its metabolites impact gastrointestinal function and contribute to the pathogenesis of digestive diseases. Further metagenomic analyses of the gastrointestinal mycobiome in health and disease is needed.}, }
@article {pmid24603797, year = {2014}, author = {Ley, RE}, title = {Harnessing microbiota to kill a pathogen: the sweet tooth of Clostridium difficile.}, journal = {Nature medicine}, volume = {20}, number = {3}, pages = {248-249}, pmid = {24603797}, issn = {1546-170X}, mesh = {Anti-Bacterial Agents/*adverse effects ; Clostridioides difficile ; Clostridium Infections/*microbiology/*therapy ; Diarrhea/chemically induced/*therapy ; Feces/microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Microbiota ; Probiotics/therapeutic use ; Sialic Acids/metabolism ; Transplantation/methods ; }, }
@article {pmid24603796, year = {2014}, author = {Taur, Y and Pamer, EG}, title = {Harnessing microbiota to kill a pathogen: Fixing the microbiota to treat Clostridium difficile infections.}, journal = {Nature medicine}, volume = {20}, number = {3}, pages = {246-247}, pmid = {24603796}, issn = {1546-170X}, support = {K23 AI095398/AI/NIAID NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antibiosis ; Bile Acids and Salts/chemistry ; Clostridioides difficile ; Clostridium Infections/*microbiology/*therapy ; Feces/*microbiology ; Humans ; Intestine, Small/*microbiology ; Mice ; Microbial Consortia ; Probiotics/*therapeutic use ; Transplantation/methods ; }, }
@article {pmid24587820, year = {2014}, author = {Khanna, S and Pardi, DS}, title = {Clostridium difficile infection: management strategies for a difficult disease.}, journal = {Therapeutic advances in gastroenterology}, volume = {7}, number = {2}, pages = {72-86}, pmid = {24587820}, issn = {1756-283X}, abstract = {Clostridium difficile was first described as a cause of diarrhea in 1978 and in the last three decades has reached an epidemic state with increasing incidence and severity in both healthcare and community settings. There also has been a rise in severe outcomes from C. difficile infection (CDI). There have been tremendous advancements in the field of CDI with the identification of newer risk factors, recognition of CDI in populations previously thought not at risk and development of better diagnostic modalities. Several treatment options are available for CDI apart from metronidazole and vancomycin, and include new drugs such as fidaxomicin and other options such as fecal microbiota transplantation. This review discusses the epidemiology, risk factors and outcomes from CDI, and focuses primarily on existing and evolving treatment modalities.}, }
@article {pmid24583610, year = {2014}, author = {König, J and Brummer, RJ}, title = {Alteration of the intestinal microbiota as a cause of and a potential therapeutic option in irritable bowel syndrome.}, journal = {Beneficial microbes}, volume = {5}, number = {3}, pages = {247-261}, doi = {10.3920/BM2013.0033}, pmid = {24583610}, issn = {1876-2891}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Feces/microbiology ; Humans ; Intestinal Mucosa/*microbiology ; Irritable Bowel Syndrome/drug therapy/*microbiology/pathology ; Microbiota/*drug effects/*immunology ; Prebiotics ; Probiotics/therapeutic use ; Synbiotics ; }, abstract = {The intestinal microbiota forms a complex ecosystem that is in close contact with its host and has an important impact on health. An increasing number of disorders are associated with disturbances in this ecosystem. Also patients suffering from irritable bowel syndrome (IBS) show an altered composition of their gut microbiota. IBS is a multifactorial chronic disorder characterised by various abdominal complaints and a worldwide prevalence of 10-20%. Even though its aetiology and pathophysiology are complex and not well understood, it is widely accepted that aberrations along the microbe-gut-brain axis are involved. In this review, it will be discussed how exogenous factors, e.g. antibiotics, can cause disbalance in the intestinal microbiota and thereby contribute to the development of IBS. In addition, several new IBS treatment options that aim at re-establishing a healthy, beneficial ecosystem will be described. These include antibiotics, probiotics, prebiotics and faecal transplantation.}, }
@article {pmid24582877, year = {2014}, author = {Austin, M and Mellow, M and Tierney, WM}, title = {Fecal microbiota transplantation in the treatment of Clostridium difficile infections.}, journal = {The American journal of medicine}, volume = {127}, number = {6}, pages = {479-483}, doi = {10.1016/j.amjmed.2014.02.017}, pmid = {24582877}, issn = {1555-7162}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/drug therapy/microbiology/*therapy ; Feces/*microbiology ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {In recent years, Clostridium difficile infections have become more frequent, more severe, more refractory to standard treatment, and more likely to recur. Current antibiotic treatment regimens for Clostridium difficile infection alter the normal gut flora, which provide colonization resistance against Clostridium difficile. Over the past few years, there has been a marked increase in the knowledge of the gut microbiota and its role in health maintenance and disease causation. This has, fortuitously, coincided with the use of a unique microbial replacement therapy, fecal microbiota transplantation, in the treatment of patients with multiple recurrent Clostridium difficile infections. We briefly review current knowledge of the gut microbiota's functions. We then review the indications for use of fecal microbiota transplantation in Clostridium difficile infection, the techniques employed, and results of treatment. Fecal microbiota transplantation has been shown to be efficacious for patients with multiply recurrent Clostridium difficile infections (reported cure rates of 90%), with an excellent short-term safety profile, and has been included in the American College of Gastroenterology treatment guidelines for this troublesome disease.}, }
@article {pmid24582649, year = {2014}, author = {Samuel, BP and Crumb, TL and Duba, MM}, title = {What nurses need to know about fecal microbiota transplantation: education, assessment, and care for children and young adults.}, journal = {Journal of pediatric nursing}, volume = {29}, number = {4}, pages = {354-361}, doi = {10.1016/j.pedn.2014.01.013}, pmid = {24582649}, issn = {1532-8449}, mesh = {Adolescent ; Child ; Child, Preschool ; Clostridium Infections/diagnosis/*therapy ; Education, Nursing, Continuing/methods ; Fecal Microbiota Transplantation/*methods/nursing ; Female ; Humans ; Male ; Nurse's Role ; Nursing Assessment ; *Patient Education as Topic ; Patient Positioning ; Pediatric Nursing/*education ; Quality Control ; Recurrence ; Risk Assessment ; Therapies, Investigational ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is an emerging experimental therapy for treatment of recurrent Clostridium difficile infection. In the future, FMT has the potential to be a treatment modality in other diseases that involve gut dysbiosis. As use of FMT is likely to expand, pediatric nurses need a clear understanding of FMT to provide appropriate education, assessment, and care for these patients. Pediatric research and clinical nurses are a resource to help children and parents understand the procedure. Important topics include donor screening, patient assessment before, during, and after treatment; routes of administration and positioning; preparation for discharge and followup evaluation.}, }
@article {pmid24582493, year = {2014}, author = {Raghavan, S and Miyasaka, EA and Gilmont, RR and Somara, S and Teitelbaum, DH and Bitar, KN}, title = {Perianal implantation of bioengineered human internal anal sphincter constructs intrinsically innervated with human neural progenitor cells.}, journal = {Surgery}, volume = {155}, number = {4}, pages = {668-674}, pmid = {24582493}, issn = {1532-7361}, support = {R01 DK071614/DK/NIDDK NIH HHS/United States ; R01DK071614/DK/NIDDK NIH HHS/United States ; 1RC1DK087151/DK/NIDDK NIH HHS/United States ; T32 HD007505/HD/NICHD NIH HHS/United States ; T32HD007505/HD/NICHD NIH HHS/United States ; RC1 DK087151/DK/NIDDK NIH HHS/United States ; }, mesh = {Anal Canal/*cytology/*innervation/*surgery ; Animals ; *Bioengineering ; Cells, Cultured ; Electric Stimulation ; Feasibility Studies ; Fecal Incontinence/therapy ; Humans ; Male ; Models, Animal ; Nerve Net/metabolism ; Neurons/*cytology ; Rats ; Rats, Nude ; Stem Cells/*cytology ; Tissue Transplantation/methods ; Vasoactive Intestinal Peptide/metabolism ; }, abstract = {BACKGROUND: The internal anal sphincter (IAS) is a major contributing factor to pressure within the anal canal and is required for maintenance of rectoanal continence. IAS damage or weakening results in fecal incontinence. We have demonstrated that bioengineered, intrinsically innervated, human IAS tissue replacements possess key aspects of IAS physiology, such as the generation of spontaneous basal tone and contraction/relaxation in response to neurotransmitters. The objective of this study is to demonstrate the feasibility of implantation of bioengineered IAS constructs in the perianal region of athymic rats.<br><br>METHODS: Human IAS tissue constructs were bioengineered from isolated human IAS circular smooth muscle cells and human enteric neuronal progenitor cells. After maturation of the bioengineered constructs in culture, they were implanted operatively into the perianal region of athymic rats. Platelet-derived growth factor was delivered to the implanted constructs through a microosmotic pump. Implanted constructs were retrieved from the animals 4 weeks postimplantation.<br><br>RESULTS: Animals tolerated the implantation well, and there were no early postoperative complications. Normal stooling was observed during the implantation period. At harvest, implanted constructs were adherent to the perirectal rat tissue and appeared healthy and pink. Immunohistochemical analysis revealed neovascularization. Implanted smooth muscle cells maintained contractile phenotype. Bioengineered constructs responded in vitro in a tissue chamber to neuronally evoked relaxation in response to electrical field stimulation and vasoactive intestinal peptide, indicating the preservation of neuronal networks.<br><br>CONCLUSION: Our results indicate that bioengineered innervated IAS constructs can be used to augment IAS function in an animal model. This is a regenerative medicine based therapy for fecal incontinence that would directly address the dysfunction of the IAS muscle.}, }
@article {pmid26624906, year = {2014}, author = {Sammons, JS and Gerber, JS and Tamma, PD and Sandora, TJ and Beekmann, SE and Polgreen, PM and Hersh, AL}, title = {Diagnosis and Management of Clostridium difficile Infection by Pediatric Infectious Diseases Physicians.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {3}, number = {1}, pages = {43-48}, doi = {10.1093/jpids/pit065}, pmid = {26624906}, issn = {2048-7207}, abstract = {BACKGROUND: The incidence of C difficile infection (CDI) has risen among children; however, optimal management of CDI within a diverse pediatric population remains unclear. Although adult guidelines recommend oral vancomycin for treatment of second recurrence or severe CDI, dedicated pediatric data to support pediatric specific management guidelines are lacking. Our objective was to describe current CDI management practices by pediatric infectious diseases (ID) physicians.<br><br>METHODS: We surveyed pediatric members of the Emerging Infections Network, a network of infectious diseases (ID) physicians across North America, in October 2012. Clinical vignettes were used to determine how physicians modify CDI management based on clinical presentation or presence of comorbidities, including solid organ transplantation, inflammatory bowel disease, and neutropenia.<br><br>RESULTS: Of the 285 physicians surveyed, 167 (59%) responded. There were no significant differences in geography, level of experience, or hospital type between respondents and non-respondents. All respondents (100%) used oral metronidazole for the initial occurrence of mild CDI in a normal host. Management varied substantially for mild CDI in patients with a variety of comorbidities, in whom metronidazole therapy was less frequently preferred (41-79%). For management of severe CDI, 65% preferred oral vancomycin alone or in combination with at least one other agent. For a second recurrence, oral vancomycin alone or in combination was preferred by 92%. Among 125 respondents who reported using alternative therapies for recurrent or severe CDI, 23 (18%) recommend fecal microbiota transplantation, while 20 (16%) reported using fidaxomicin.<br><br>CONCLUSIONS: Pediatric ID physicians prefer metronidazole for treatment of mild CDI in healthy children, but management strategies vary for patients with comorbidities or recurrent or severe disease. These findings highlight the need for pediatric comparative effectiveness studies aimed at determining the optimal treatment for pediatric CDI.}, }
@article {pmid24577353, year = {2014}, author = {Fuentes, S and van Nood, E and Tims, S and Heikamp-de Jong, I and ter Braak, CJ and Keller, JJ and Zoetendal, EG and de Vos, WM}, title = {Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection.}, journal = {The ISME journal}, volume = {8}, number = {8}, pages = {1621-1633}, pmid = {24577353}, issn = {1751-7370}, mesh = {*Clostridioides difficile ; Clostridium Infections/*microbiology/therapy ; Feces/*microbiology ; Humans ; Intestines/microbiology ; *Microbiota ; Phylogeny ; Recurrence ; }, abstract = {Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time. Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies.}, }
@article {pmid24574795, year = {2014}, author = {Hold, GL and Smith, M and Grange, C and Watt, ER and El-Omar, EM and Mukhopadhya, I}, title = {Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years?.}, journal = {World journal of gastroenterology}, volume = {20}, number = {5}, pages = {1192-1210}, pmid = {24574795}, issn = {2219-2840}, mesh = {Animals ; Bacteria/drug effects/growth &amp; development/immunology/*pathogenicity ; Colitis, Ulcerative/genetics/immunology/*microbiology/therapy ; Crohn Disease/genetics/immunology/*microbiology/therapy ; Dysbiosis ; Genetic Predisposition to Disease ; Humans ; Immunity, Innate/genetics ; Immunity, Mucosal/genetics ; Intestines/immunology/*microbiology ; Microbiota ; Phenotype ; Polymorphism, Single Nucleotide ; Risk Factors ; }, abstract = {Our understanding of the microbial involvement in inflammatory bowel disease (IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn's disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or "dysbiosis" is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity (including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.}, }
@article {pmid24560289, year = {2014}, author = {Amarenco, G and Gamé, X and Petit, AC and Fatton, B and Jeandel, C and Robain, G and Scheiber-Nogueira, C and Vetel, JM and Mares, P and , }, title = {[Guidelines concerning urinary incontinence in elderly: construction and validation of GRAPPPA algorithm].}, journal = {Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie}, volume = {24}, number = {4}, pages = {215-221}, doi = {10.1016/j.purol.2013.11.016}, pmid = {24560289}, issn = {1166-7087}, mesh = {Aged ; *Algorithms ; Humans ; Urinary Incontinence/*diagnosis/*therapy ; }, abstract = {OBJECTIVES: Provide guidelines presented as an algorithm for practical evaluation and first line therapy of urinary incontinence in elderly.<br><br>PATIENTS AND METHODS: Guidelines using formalized consensus guidelines method. These guidelines have been validated by a group of 40 experts quoting proposals, subsequently reviewed by an independent group of multidisciplinary experts (urologist, general practitioner, neurologist, gynecologist, geriatrist, specialist in physical medicine and rehabilitation).<br><br>RESULTS: By means of 3 rounds of interrogation of the expert panel, GRAPPPA algorithm was constructed. This algorithm take in account both evaluation and first line therapeutic options in the different type of incontinences observed in this population (urge, stress and mixed incontinence). Initial evaluation consists to track down urinary retention (and subsequently fecal stool impaction, use of anticholinergic or morphinic drugs), urinary tract infection and cognitive impairment. Haematuria, bladder-pelvic pain, history of radiotherapy or recent pelvic surgery, lead to refer the patient to a specialized unit. First line therapy is in all the cases pelvic floor training, use of local oestrogenotherapy and dietetic measures. In urge incontinence, anticholinergic drugs may be used.<br><br>CONCLUSIONS: Implementation of this algorithm may promote best practice in management of urinary incontinence in elderly.}, }
@article {pmid24559593, year = {2014}, author = {Pires, RN and Monteiro, AA and Carneiro, LC and Baethgen, LF and Tavares, R and Lincho, CS and Park, S and Perlin, D and Rodrigues Filho, EM and Pasqualotto, AC}, title = {Clostridium difficile infection in Brazil: a neglected problem?.}, journal = {American journal of infection control}, volume = {42}, number = {4}, pages = {459-460}, doi = {10.1016/j.ajic.2013.10.012}, pmid = {24559593}, issn = {1527-3296}, mesh = {Adult ; Aged ; Aged, 80 and over ; Brazil/epidemiology ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/chemically induced/*epidemiology ; Cross Infection/chemically induced/*epidemiology ; Diarrhea/chemically induced/*epidemiology ; Feces/*microbiology ; Female ; Humans ; Male ; Middle Aged ; Neglected Diseases/chemically induced/*epidemiology ; Prevalence ; Prospective Studies ; Young Adult ; }, abstract = {The epidemiology of Clostridium difficile infection is virtually unknown in Brazil. In this prospective study, 8.3% of patients with nosocomial diarrhea were found to have toxigenic strains of C difficile in their feces. The relevant risk factors for Clostridium difficile infection were receipt of solid organ transplantation and septic shock.}, }
@article {pmid24558901, year = {2014}, author = {Voide, C and Asner, S and Giulieri, S and Cavassini, M and Merz, L and Tissot, F and Orasch, C}, title = {[Infectious diseases].}, journal = {Revue medicale suisse}, volume = {10}, number = {412-413}, pages = {61-65}, pmid = {24558901}, issn = {1660-9379}, mesh = {China/epidemiology ; *Communicable Diseases, Emerging/epidemiology/etiology/therapy ; Drug Contamination ; Drug Resistance, Microbial ; Gonorrhea/drug therapy/microbiology ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza, Human/epidemiology/virology ; Mycoses/etiology ; United States/epidemiology ; }, abstract = {The recommendations for the treatment of gonorrhea have been changed: ceftriaxone 500 mg IM plus azithromycin 1 g PO is recommended. Prophylaxis of recurrent cellulitis with penicillin 250 mg 2 x/d PO may be considered. E. coli ESBL does not require contact isolation anymore. Fecal transplantation seems so far to be the most effective treatment of recurrent C. dificile. Two new respiratory viruses, Middle East Coronavirus (MERS-CoV) and avian-origin Influenza A (H7N9) have been reported. Oral valganciclovir treatment reduces the risk of hearing loss in congenital CMV infection. An outbreak of mould infections of the central nervous system has been described in the United States following injection of contaminated steroids.}, }
@article {pmid24558658, year = {2014}, author = {Smith, MB and Kelly, C and Alm, EJ}, title = {Policy: How to regulate faecal transplants.}, journal = {Nature}, volume = {506}, number = {7488}, pages = {290-291}, doi = {10.1038/506290a}, pmid = {24558658}, issn = {1476-4687}, mesh = {Animals ; Clostridioides difficile/pathogenicity ; Clostridium Infections/microbiology/*therapy ; Compassionate Use Trials/legislation &amp; jurisprudence ; Controlled Clinical Trials as Topic/legislation &amp; jurisprudence ; Feces/*microbiology ; Humans ; Mice ; Microbiota/physiology ; Tissue Transplantation/adverse effects/classification/*legislation &amp; jurisprudence ; United States ; United States Food and Drug Administration/legislation &amp; jurisprudence ; }, }
@article {pmid24555086, year = {2013}, author = {Myers-Morales, T and Bussell, KM and D'Orazio, SE}, title = {Fecal transplantation does not transfer either susceptibility or resistance to food borne listeriosis in C57BL/6 and BALB/c/By mice.}, journal = {F1000Research}, volume = {2}, number = {}, pages = {177}, pmid = {24555086}, issn = {2046-1402}, support = {R01 AI101373/AI/NIAID NIH HHS/United States ; }, abstract = {The composition of the intestinal microbiota has wide reaching effects on the health of an individual, including the development of protective innate immune responses. In this report, a fecal transplantation approach was used to determine whether resistance to food borne listeriosis was dependent on the murine gut microbiota. Transplantation of BALB/c/By feces did not increase the susceptibility of C57BL/6 mice to Listeria monocytogenes infection. Likewise, transplantation of C57BL/6 fecal matter did not enhance the resistance of BALB/c/By mice. Thus, intestinal microbiota composition is not a key factor that confers either susceptibility or resistance to food borne listeriosis in mice.}, }
@article {pmid24529606, year = {2014}, author = {Brace, C and Gloor, GB and Ropeleski, M and Allen-Vercoe, E and Petrof, EO}, title = {Microbial composition analysis of Clostridium difficile infections in an ulcerative colitis patient treated with multiple fecal microbiota transplantations.}, journal = {Journal of Crohn's &amp; colitis}, volume = {8}, number = {9}, pages = {1133-1137}, doi = {10.1016/j.crohns.2014.01.020}, pmid = {24529606}, issn = {1876-4479}, mesh = {Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Colitis, Ulcerative/complications/diagnosis/*microbiology ; Enterocolitis, Pseudomembranous/complications/diagnosis/*microbiology ; Feces/microbiology ; Humans ; Male ; *Microbiota ; Sigmoidoscopy ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising therapy for Clostridium difficile infection (CDI). However, questions remain regarding efficacy and safety in inflammatory bowel disease (IBD) patients, as well as longitudinal stability of donor stool composition. This report describes an IBD patient with two CDIs 18 months apart, each successfully treated with FMT with no IBD flares or complications. Microbiome composition analysis of patient samples during each infection revealed low-diversity microbiota patterns similar to those previously described in non-IBD patients with CDI and active IBD alone. Samples taken after each transplant demonstrated quick remodeling towards the donor's sample composition coinciding with symptom resolution. Of note, samples taken from the same donor 18 months apart reflected marked differences in microbiota abundances, suggesting that the use of single donors in FMT programs offers little benefit in ensuring predictability of donor stool composition over time. This report describes similar microbial composition patterns during CDI in IBD patients to those described previously in non-IBD patients, and supports FMT as safe and effective treatment for recurring CDI in this patient population.}, }
@article {pmid24528224, year = {2014}, author = {Udayappan, SD and Hartstra, AV and Dallinga-Thie, GM and Nieuwdorp, M}, title = {Intestinal microbiota and faecal transplantation as treatment modality for insulin resistance and type 2 diabetes mellitus.}, journal = {Clinical and experimental immunology}, volume = {177}, number = {1}, pages = {24-29}, pmid = {24528224}, issn = {1365-2249}, mesh = {Animals ; Butyrates/*immunology ; Diabetes Mellitus, Type 2/immunology/microbiology/*therapy ; Feces/*microbiology ; Humans ; Insulin Resistance/immunology ; Intestines/*immunology ; Lipid Metabolism ; Microbiota/*immunology ; Transplantation ; }, abstract = {The prevalence of obesity and diabetes mellitus type 2 is increasing rapidly around the globe. Recent insights have generated an entirely new perspective that the intestinal microbiota may play a significant role in the development of these metabolic disorders. Alterations in the intestinal microbiota composition promote systemic inflammation that is a hallmark of obesity and subsequent insulin resistance. Thus, it is important to understand the reciprocal relationship between intestinal microbiota composition and metabolic health in order to eventually prevent disease progression. In this respect, faecal transplantation studies have implicated that butyrate-producing intestinal bacteria are crucial in this process and be considered as key players in regulating diverse signalling cascades associated with human glucose and lipid metabolism.}, }
@article {pmid24510892, year = {2013}, author = {Marsh, JW and Curry, SR}, title = {Therapeutic approaches for Clostridium difficile infections.}, journal = {Current protocols in microbiology}, volume = {30}, number = {}, pages = {9A.3.1-9A.3.9}, doi = {10.1002/9780471729259.mc09a03s30}, pmid = {24510892}, issn = {1934-8533}, mesh = {Aminoglycosides/therapeutic use ; Anti-Infective Agents/therapeutic use ; Antibodies, Bacterial/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antitoxins/therapeutic use ; Bacterial Vaccines/therapeutic use ; Biological Therapy/methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*microbiology/*therapy ; Diarrhea/*drug therapy/*microbiology ; Drug Therapy/methods ; Fidaxomicin ; Humans ; Immunotherapy/methods ; Metronidazole/therapeutic use ; Vancomycin/therapeutic use ; }, abstract = {Metronidazole and vancomycin remain the front-line therapies for most Clostridium difficile infections (CDI). However, recurrent CDI occurs in ∼ 25% of patients, causing significant morbidity and mortality and healthcare costs. For this population, traditional antibiotic therapies fail and new treatment options are greatly needed. The US Food and Drug Administration recently approved fidaxomicin for CDI treatment. This narrow-spectrum antibiotic preserves the normal gut microbiota and shows promise as a treatment for severe and recurrent CDI. Monoclonal antibodies and vaccines directed against toxin are currently in clinical trials and represent alternative, non-antibiotic therapies. Less traditional therapeutic interventions include bacteriotherapy with non-toxigenic C. difficile and fecal transplant. This commentary will provide an overview of current and forthcoming CDI therapies.}, }
@article {pmid24506850, year = {2014}, author = {Huang, W and Wan, X}, title = {[Update of critical care medicine 2013].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {26}, number = {1}, pages = {3-10}, doi = {10.3760/cma.j.issn.2095-4352.2014.01.002}, pmid = {24506850}, issn = {2095-4352}, mesh = {*Critical Care ; Humans ; Treatment Outcome ; }, abstract = {The present review concluded remarkable globe clinical achievements in the field of critical care medicine during 2013. Briefly, new international sepsis management guideline, high frequency oscillatory ventilation, hydroxyethyl starch, immune-nutritional therapy, fecal transplantation and infection controlling became the highlighting topics. Additionally, it is also worthy to note the apparent disparity in the results between meta-analyses suggesting a treatment advantage and following large-scale randomized trials that have failed to detect such differences in treatment outcomes. Nonetheless, we still expect the emerging of ongoing investigations may provide clarity in these area..}, }
@article {pmid24505094, year = {2015}, author = {Garg, M and Burrell, LM and Velkoska, E and Griggs, K and Angus, PW and Gibson, PR and Lubel, JS}, title = {Upregulation of circulating components of the alternative renin-angiotensin system in inflammatory bowel disease: A pilot study.}, journal = {Journal of the renin-angiotensin-aldosterone system : JRAAS}, volume = {16}, number = {3}, pages = {559-569}, doi = {10.1177/1470320314521086}, pmid = {24505094}, issn = {1752-8976}, mesh = {Adult ; Aged ; Angiotensin I/blood ; Angiotensin-Converting Enzyme 2 ; Biomarkers/blood ; Case-Control Studies ; Female ; Humans ; Inflammatory Bowel Diseases/*blood ; Male ; Middle Aged ; Peptide Fragments/blood ; Peptidyl-Dipeptidase A/blood ; Pilot Projects ; *Renin-Angiotensin System ; *Up-Regulation ; Young Adult ; }, abstract = {INTRODUCTION: The relationship between intestinal inflammation and circulating components of the renin-angiotensin system (RAS) is poorly understood.<br><br>MATERIALS AND METHODS: Demographic and clinical data were obtained from healthy controls and patients with inflammatory bowel disease (IBD). Plasma concentrations of the classical RAS components (angiotensin-converting enzyme (ACE) and angiotensin II (Ang II)) and alternative RAS components (ACE2 and angiotensin (1-7) (Ang (1-7))) were analysed by radioimmuno- and enzymatic assays. Systemic inflammation was assessed using serum C-reactive protein (CRP), white cell count, platelet count and albumin, and intestinal inflammation by faecal calprotectin.<br><br>RESULTS: Nineteen healthy controls (11 female; mean age 38 years, range 23-68), 19 patients with Crohn's disease (11 female; aged 45 years, range 23-76) and 15 patients with ulcerative colitis (6 female; aged 42 years, 26-64) were studied. Circulating classical RAS component levels were similar across the three groups, whereas ACE2 activity and Ang (1-7) concentrations were higher in patients with IBD compared to controls (ACE2: 21.5 vs 13.3 pmol/ml/min, p<0.05; Ang (1-7): 22.8 vs 14.1 pg/ml, p<0.001). Ang (1-7) correlated weakly with platelet and white cell counts, but not calprotectin or CRP, in patients with IBD.<br><br>CONCLUSIONS: Circulating components of the alternative RAS are increased in patients with IBD.}, }
@article {pmid24492144, year = {2014}, author = {Holler, E and Butzhammer, P and Schmid, K and Hundsrucker, C and Koestler, J and Peter, K and Zhu, W and Sporrer, D and Hehlgans, T and Kreutz, M and Holler, B and Wolff, D and Edinger, M and Andreesen, R and Levine, JE and Ferrara, JL and Gessner, A and Spang, R and Oefner, PJ}, title = {Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {20}, number = {5}, pages = {640-645}, pmid = {24492144}, issn = {1523-6536}, support = {P01 CA039542/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Biodiversity ; Enterococcus faecalis/drug effects/genetics ; Enterococcus faecium/drug effects/genetics ; Feces/microbiology ; Female ; Gastrointestinal Tract/drug effects/immunology/*microbiology ; Graft vs Host Disease/drug therapy/immunology/*microbiology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Indican/urine ; Male ; *Metagenome ; Microbiota ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Transplantation, Homologous ; }, abstract = {Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 μmol/L to 11.8 ± 2.8 μmol/L in all post-transplant samples and to 3.5 ± 3 μmol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT.}, }
@article {pmid24486051, year = {2014}, author = {Shanahan, F and Quigley, EM}, title = {Manipulation of the microbiota for treatment of IBS and IBD-challenges and controversies.}, journal = {Gastroenterology}, volume = {146}, number = {6}, pages = {1554-1563}, doi = {10.1053/j.gastro.2014.01.050}, pmid = {24486051}, issn = {1528-0012}, mesh = {Animals ; *Biological Therapy/adverse effects ; Dysbiosis ; Feces/microbiology ; Host-Pathogen Interactions ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Intestines/*microbiology ; Irritable Bowel Syndrome/microbiology/*therapy ; *Microbiota ; *Prebiotics/adverse effects ; Probiotics/adverse effects/*therapeutic use ; Treatment Outcome ; }, abstract = {There is compelling rationale for manipulating the microbiota to treat inflammatory bowel diseases (IBDs). Although studies of animal models of intestinal inflammation produced promising results, trials in humans have been disappointing. In contrast to IBD, the role of the microbiota in the development of irritable bowel syndrome (IBS) only recently has been considered, but early stage results have been encouraging. As pharmaceutical companies develop fewer truly novel agents for treatment of these disorders, consumers seek safer, long-term strategies to deal with chronic symptoms. We assess the rationale for modulating the microbiota for treatment of IBD and IBS, and discuss whether current concepts are simplistic and overstated or simply under-researched. Are claims exaggerated and expectations unrealistic? Difficulties with microbiota terminology and technologies, as well as differences among patients and the heterogeneity of these diseases, pose additional challenges in developing microbiota-based therapies for IBD and IBS.}, }
@article {pmid24485251, year = {2014}, author = {Navez, B and Navez, J}, title = {Laparoscopy in the acute abdomen.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {28}, number = {1}, pages = {3-17}, doi = {10.1016/j.bpg.2013.11.006}, pmid = {24485251}, issn = {1532-1916}, mesh = {Abdomen, Acute/diagnosis/etiology/*surgery ; Digestive System Surgical Procedures/adverse effects/*methods ; Emergencies ; Humans ; *Laparoscopy/adverse effects ; Patient Selection ; Postoperative Complications/prevention &amp; control ; Risk Factors ; Treatment Outcome ; }, abstract = {Laparoscopy has become a routine procedure in the management of acute abdominal disease and can be considered both an excellent therapeutic and additional diagnostic tool in selected cases. However, a high level of expertise in laparoscopic and emergency surgery is required. Hemodynamic instability, huge abdominal distension, fecal peritonitis and perforated cancer are relative contraindications for the laparoscopic approach. In recent years, abdominal emergencies have increasingly been managed successfully by laparoscopy. In acute appendicitis, acute cholecystitis and perforated peptic ulcer, randomized controlled trials have proven that the laparoscopic approach is as safe and as effective as open surgery, with fewer complications and a quicker postoperative recovery. Other indications such as blunt and penetrating trauma to the abdomen, small bowel occlusion and perforated diverticular disease are under debate, indicating that more randomized controlled trials comparing laparoscopic and open surgery are still necessary.}, }
@article {pmid24481438, year = {2014}, author = {Halabe Cherem, J and Hoyo Ulloa, I}, title = {[Successful home-made fecal transplant for an elderly woman].}, journal = {Gaceta medica de Mexico}, volume = {150}, number = {1}, pages = {106-107}, pmid = {24481438}, issn = {0016-3813}, mesh = {Aged, 80 and over ; Clostridium Infections/*therapy ; *Feces ; Female ; Humans ; Remission Induction ; }, abstract = {Recurrent clostridium difficile infection (CDI) is a challenge for infectious disease specialists. A third of first recurrences will fail antibiotic therapy. Several mechanisms have been proposed to explain this, such as persistence of spores, inadequate antibody response, and altered gut microbiota. Standard recommendations for CDI treatment include metronidazole and vancomycin. Fecal transplant has proven to be an effective therapy for recurrent CDI. Infusion of stools can be administered to the upper or lower gastrointestinal tract during an endoscopic procedure or using nasogastric/duodenal or rectal tubes. Elderly persons have an increased incidence of recurrent infection and have a higher mortality rate. We propose a home-based delivery method using a 5 ml syringe for intrarectal infusion of stools.}, }
@article {pmid24474632, year = {2014}, author = {Singh, A and Gora, N and Soni, ML and Khandelwal, RG and Vidyarthi, SH and Thounaojam, CK and Sharma, U}, title = {Comparative study of free omental sheet graft and other operative procedures of enteric perforation repair.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {18}, number = {4}, pages = {751-756}, pmid = {24474632}, issn = {1873-4626}, mesh = {Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; India ; Intestinal Fistula/*etiology ; Intestinal Perforation/microbiology/mortality/*surgery ; Male ; Middle Aged ; Omentum/*transplantation ; Peritonitis/*etiology ; Postoperative Complications/*etiology ; Respiratory Tract Diseases/etiology ; Retrospective Studies ; Sepsis/etiology ; Surgical Wound Dehiscence/etiology ; Surgical Wound Infection/etiology ; Typhoid Fever/*complications ; Young Adult ; }, abstract = {BACKGROUND/AIM: In developing countries, enteric perforation due to typhoid continues to have very high morbidity and mortality rates irrespective of the type of operative procedure performed. The aim of the present study was to evaluate the effectiveness of a free omental sheet graft in perforated typhoid enteritis, in comparison to other methods of enteric perforation repair in terms of decreased morbidity, mortality and cost-effectiveness.<br><br>METHOD: A non-randomized study of 114 patients with enteric perforations was carried out over a period of 4.5 years. The study was divided in two groups; group I includes 38 cases in which a free omental sheet graft was used in typhoid enteritis with perforation and group II includes 76 cases in which other surgical procedures for enteric perforation repair were used. The outcomes were measured in relation to postoperative complications and mortality.<br><br>RESULTS: The incidence of complications including faecal fistula was 2.6% in group I (free omental sheet graft group) versus 32.89% in group II. The mortality rate of 2.6% was also lower in group I versus 19.7% in group II.<br><br>CONCLUSION: This study concludes that the use of free omental sheet graft on typhoid enteric perforation site is effective in lowering the repair leak rate and thereby decreases the morbidity and mortality associated with these procedures. By lowering the complication rates, it also entails reduction in financial burden.}, }
@article {pmid24474190, year = {2014}, author = {Eppinga, H and Konstantinov, SR and Peppelenbosch, MP and Thio, HB}, title = {The microbiome and psoriatic arthritis.}, journal = {Current rheumatology reports}, volume = {16}, number = {3}, pages = {407}, pmid = {24474190}, issn = {1534-6307}, mesh = {Anti-Bacterial Agents/therapeutic use ; Arthritis, Psoriatic/drug therapy/immunology/*microbiology ; Autoimmunity ; Feces/microbiology ; Fungi/isolation &amp; purification ; Humans ; Intestines/microbiology ; *Microbiota/immunology ; Probiotics/therapeutic use ; Skin/microbiology ; Symbiosis ; T-Lymphocyte Subsets/immunology ; Tissue Transplantation/methods ; }, abstract = {Psoriatic arthritis is a chronic inflammatory joint disease, seen in combination with the chronic inflammatory skin disease psoriasis and belonging to the family of spondylarthritides (SpA). A link is recognized between psoriatic arthritis and inflammatory bowel disease (IBD). Environmental factors seem to induce inflammatory disease in individuals with underlying genetic susceptibility. The microbiome is a subject of increasing interest in the etiology of these inflammatory immune-mediated diseases. The intestinal microbiome is able to affect extra-intestinal distant sites, including the joints, through immunomodulation. At this point, evidence regarding a relationship between the microbiome and psoriatic arthritis is scarce. However, we hypothesize that common immune-mediated inflammatory pathways seen in the "skin-joint-gut axis" in psoriatic arthritis are induced or at least mediated by the microbiome. Th17 has a crucial function in this mechanism. Further establishment of this connection may lead to novel therapeutic approaches for psoriatic arthritis.}, }
@article {pmid24470963, year = {2013}, author = {Di Bella, S and Drapeau, C and García-Almodóvar, E and Petrosillo, N}, title = {Fecal microbiota transplantation: the state of the art.}, journal = {Infectious disease reports}, volume = {5}, number = {2}, pages = {e13}, pmid = {24470963}, issn = {2036-7430}, abstract = {Clostridium difficile infection (CDI) is an emerging problem in terms of incidence, morbidity and mortality. Currently available treatment options are not always effective, especially in cases of recurrent/refractory or complicated CDI. The gut microbiota transplantation is a technique that has been sporadically practiced since the '50s, but its clinical efficacy has only recently been supported by scientific evidence. In the present article, we report the pathophysiological basis and the clinical indications of this technique that, in light of its low cost, and proven efficacy and safety, is likely to become part of the management guidelines of difficult cases of CDI in the near future.}, }
@article {pmid24467987, year = {2013}, author = {Petrof, EO and Gloor, GB and Vanner, SJ and Weese, SJ and Carter, D and Daigneault, MC and Brown, EM and Schroeter, K and Allen-Vercoe, E}, title = {Stool substitute transplant therapy for the eradication of Clostridium difficile infection: 'RePOOPulating' the gut.}, journal = {Microbiome}, volume = {1}, number = {1}, pages = {3}, pmid = {24467987}, issn = {2049-2618}, abstract = {BACKGROUND: Fecal bacteriotherapy ('stool transplant') can be effective in treating recurrent Clostridium difficile infection, but concerns of donor infection transmission and patient acceptance limit its use. Here we describe the use of a stool substitute preparation, made from purified intestinal bacterial cultures derived from a single healthy donor, to treat recurrent C. difficile infection that had failed repeated standard antibiotics. Thirty-three isolates were recovered from a healthy donor stool sample. Two patients who had failed at least three courses of metronidazole or vancomycin underwent colonoscopy and the mixture was infused throughout the right and mid colon. Pre-treatment and post-treatment stool samples were analyzed by 16 S rRNA gene sequencing using the Ion Torrent platform.<br><br>RESULTS: Both patients were infected with the hyper virulent C. difficile strain, ribotype 078. Following stool substitute treatment, each patient reverted to their normal bowel pattern within 2 to 3&#x2009;days and remained symptom-free at 6&#x2009;months. The analysis demonstrated that rRNA sequences found in the stool substitute were rare in the pre-treatment stool samples but constituted over 25% of the sequences up to 6&#x2009;months after treatment.<br><br>CONCLUSION: This proof-of-principle study demonstrates that a stool substitute mixture comprising a multi-species community of bacteria is capable of curing antibiotic-resistant C. difficile colitis. This benefit correlates with major changes in stool microbial profile and these changes reflect isolates from the synthetic mixture.<br><br>CinicalTrials.gov NCT01372943.}, }
@article {pmid24465506, year = {2014}, author = {Chong, Y and Shimoda, S and Yakushiji, H and Ito, Y and Aoki, T and Miyamoto, T and Kamimura, T and Shimono, N and Akashi, K}, title = {Clinical impact of fluoroquinolone-resistant Escherichia coli in the fecal flora of hematological patients with neutropenia and levofloxacin prophylaxis.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e85210}, pmid = {24465506}, issn = {1932-6203}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Drug Resistance, Bacterial/drug effects ; Escherichia coli/*drug effects/isolation &amp; purification/physiology ; Escherichia coli Infections/complications/microbiology/*prevention &amp; control ; Febrile Neutropenia/*complications ; Feces/*microbiology ; Female ; Hematologic Neoplasms/*complications ; Host-Pathogen Interactions/drug effects ; Humans ; Levofloxacin/*therapeutic use ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Fluoroquinolone prophylaxis in patients with neutropenia and hematological malignancies is said to be effective on febrile netropenia (FN)-related infection and mortality; however, the emergence of antibiotic resistance has become a concern. Ciprofloxacin and levofloxacin prophylaxis are most commonly recommended. A significant increase in the rate of quinolone-resistant Escherichia coli in fecal flora has been reported following ciprofloxacin prophylaxis. The acquisition of quinolone-resistant E. coli after levofloxacin use has not been evaluated.<br><br>METHODS: We prospectively examined the incidence of quinolone-resistant E. coli isolates recovered from stool cultures before and after levofloxacin prophylaxis in patients with neutropenia from August 2011 to May 2013. Some patients received chemotherapy multiple times.<br><br>RESULTS: In this trial, 68 patients were registered. Levofloxacin-resistant E. coli isolates were detected from 11 and 13 of all patients before and after the prophylaxis, respectively. However, this was not statistically significant (P&#x200a;=&#x200a;0.65). Multiple prophylaxis for sequential chemotherapy did not induce additional quinolone resistance among E. coli isolates. Interestingly, quinolone-resistant E. coli, most of which were extended-spectrum &#x3b2;-lactamase (ESBL) producers, were already detected in approximately 20% of all patients before the initiation of prophylaxis. FN-related bacteremia developed in 2 patients, accompanied by a good prognosis.<br><br>CONCLUSIONS: Levofloxacin prophylaxis for neutropenia did not result in a significant acquisition of quinolone-resistant E. coli. However, we detected previous colonization of quinolone-resistant E. coli before prophylaxis, which possibly reflects the spread of ESBL. The epidemic spread of resistant E. coli as a local factor may influence strategies toward the use of quinolone prophylaxis.}, }
@article {pmid24459443, year = {2013}, author = {Paradies, P and Schnyder, M and Capogna, A and Lia, RP and Sasanelli, M}, title = {Canine angiostrongylosis in naturally infected dogs: clinical approach and monitoring of infection after treatment.}, journal = {TheScientificWorldJournal}, volume = {2013}, number = {}, pages = {702056}, pmid = {24459443}, issn = {1537-744X}, mesh = {Animals ; Anthelmintics/*therapeutic use ; Dog Diseases/*diagnosis/*drug therapy ; Dogs ; *Severity of Illness Index ; Strongylida Infections/diagnosis/*drug therapy/*veterinary ; Treatment Outcome ; }, abstract = {Canine angiostrongylosis is an increasingly reported disease in Europe which can be fatal if left untreated. The wide range of clinical presentation along with the absence of pathognomonic alterations can make the diagnosis challenging; thus any additional information that may provide clues to an early diagnosis may be of value, in order to ensure adequate anthelmintic treatment. Aim of the study was to assess a clinicopathological scoring system associated with natural Angiostrongylus vasorum infection diagnosed in canine patients during clinical practice, to clinically and paraclinically monitor infected dogs after treatment, and to monitor the presence of L1 larvae in faecal samples by Baermann's test. Of the total 210 enrolled animals A. vasorum infection was diagnosed in 7 dogs. These dogs were clinically and paraclinically investigated and monitored after specific treatment. Further 3 symptomatic dogs were retrospectively included in the monitoring. Results suggest that the computed scoring system can help to increase the clinical suspicion of infection particularly in asymptomatic dogs before the onset of potentially lethal lesions. Data of faecal monitoring suggested that treatment may control parasite burden but be unable to eradicate infection. Thus, a continued faecal monitoring after treatment is advisable for identification of still infected or reinfected dogs.}, }
@article {pmid24457346, year = {2014}, author = {Zoetendal, EG and de Vos, WM}, title = {Effect of diet on the intestinal microbiota and its activity.}, journal = {Current opinion in gastroenterology}, volume = {30}, number = {2}, pages = {189-195}, doi = {10.1097/MOG.0000000000000048}, pmid = {24457346}, issn = {1531-7056}, mesh = {Animals ; *Diet ; Disease Models, Animal ; Feces/microbiology ; Humans ; Intestines/*microbiology ; Life Style ; Mice ; *Microbiota ; Tissue Transplantation/methods ; Translational Research, Biomedical/methods ; }, abstract = {PURPOSE OF REVIEW: To summarize and discuss recent findings concerning diet-microbiota-health relations.<br><br>RECENT FINDINGS: Mouse and other model animal studies have provided detailed insight into host-microbiota interactions, but cannot be extrapolated easily to humans that have different dietary habits, intestinal architecture, and microbiota composition. In spite of the fact that all humans have a personalized microbiome, the discovery of the high-level clusters, such as enterotypes, offer great potential for stratifying individuals in intervention studies based on their intestinal microbiota. A highly diverse microbiota seems to be key to adult human health. Long-term dietary patterns have been found to be associated with specific microbiota compositions and in some cases enterotypes. Fecal transplantations indicate that homeostasis can be restored and indicate that diet-microbiota-induced disorders can be improved by therapeutic modification of the microbiota. The specificity of complex carbohydrate conversion is the driving ecological force in the colon, while competition for sugars with the host is the driver for the small intestinal ecosystem. At both locations, the microbial fermentation of dietary components occurs in trophic chains and insight into these multispecies conversions is essential to understand the impact of diet on health.<br><br>SUMMARY: There are clear associations between the microbiota, our diet and our health. However, as microbiota correlations with human health and diet are generally based on baseline comparisons between populations, there is a need for dedicated dietary intervention studies in humans to differentiate between correlation and causality.}, }
@article {pmid24457126, year = {2014}, author = {Cammarota, G and Ianiro, G and Gasbarrini, A and Masucci, L and Sanguinetti, M}, title = {Faecal transplantation for Clostridium difficile infection. Three cases treated in Italy.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {46}, number = {5}, pages = {475}, doi = {10.1016/j.dld.2013.12.011}, pmid = {24457126}, issn = {1878-3562}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacterial Toxins/analysis ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/chemistry/*microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Male ; Metagenome ; }, }
@article {pmid24450861, year = {2014}, author = {Altomare, DF and Di Lena, M and Giuratrabocchetta, S and Giannini, I and Falagario, M and Zbar, AP and Rockwood, T}, title = {The Three Axial Perineal Evaluation (TAPE) score: a new scoring system for comprehensive evaluation of pelvic floor function.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {16}, number = {6}, pages = {459-468}, doi = {10.1111/codi.12567}, pmid = {24450861}, issn = {1463-1318}, mesh = {Adult ; Aged ; Defecation/*physiology ; Fecal Incontinence/*diagnosis/etiology/physiopathology ; Female ; Follow-Up Studies ; Gynecologic Surgical Procedures/*adverse effects ; Humans ; Middle Aged ; Pelvic Floor/*physiopathology ; Perineum/*physiopathology ; Prognosis ; ROC Curve ; Retrospective Studies ; Surveys and Questionnaires ; Treatment Outcome ; Urinary Incontinence/*diagnosis/etiology/physiopathology ; Urination/*physiology ; }, abstract = {AIM: Abnormalities of one pelvic floor compartment are usually associated with anomalies in the other compartments. Therapies which specifically address one clinical problem may potentially adversely affect other pelvic floor activities. A new comprehensive holistic scoring system defining global pelvic function is presented.<br><br>METHOD: A novel scoring system with a software program is presented expressing faecal, urinary and gynaecological functions as a geometric polygon based on symptom-specific questionnaires [the three axial pelvic evaluation (TAPE) score] where differences in overall geometric area vary from normal. After validation in healthy volunteers, its clinical performance was tested on patients with obstructed defaecation, genital prolapse and urinary/faecal incontinence treated by the stapled transanal rectal resection (STARR) procedure, colpo-hysterectomy and sacral nerve modulation, respectively. The TAPE score was correlated with the Pelvic Floor Impact Questionnaire 7 quality of life score.<br><br>RESULTS: There was good inter-observer variation and internal consistency between two observers recording the TAPE score in normal volunteers. In the STARR patients, constipation improved but the TAPE score was unchanged because of deterioration in other pelvic floor functions leading to an unchanged overall postoperative recorded quality of life. Conversely, incontinent patients treated with sacral nerve stimulation improved their function showing concomitant improvements in TAPE scores and quality of life indices. Similar correlative improvements were noted in patients undergoing hysterectomy for genital prolapse.<br><br>CONCLUSION: The TAPE score defines the impact of symptom-specific treatments on the pelvic floor and may provide an opportunity for comparison of clinical data between units and in clinical trials of specific medical and surgical pelvic floor management.}, }
@article {pmid24440934, year = {2014}, author = {Cammarota, G and Ianiro, G and Gasbarrini, A}, title = {Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review.}, journal = {Journal of clinical gastroenterology}, volume = {48}, number = {8}, pages = {693-702}, doi = {10.1097/MCG.0000000000000046}, pmid = {24440934}, issn = {1539-2031}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Diarrhea/microbiology/*therapy ; Feces/*microbiology ; Humans ; Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {GOAL: By systematic review, we assessed the impact of fecal microbiota transplantation (FMT) for the treatment of Clostridium difficile (CD)-associated diarrhea.<br><br>BACKGROUND: Fecal microbiota microbiota transplantation from a healthy donor into an individual with CD infection (CDI) can resolve symptoms.<br><br>STUDY: We conducted systematic searches in PubMed, SCOPUS, Web of Science, and Cochrane Library. The last search was run on February 8, 2013. The following Medical Subject Headings terms and keywords were used alone or in combination: Clostridium difficile; Clostridium infection; pseudomembranous colitis; feces; stools; fecal suspension; fecal transplantation; fecal transfer; fecal infusion; microbiota; bacteriotherapy; enema; nasogastric tube; colonoscopy; gastroscopy; fecal donation; donor. A critical appraisal of the clinical research evidence on the effectiveness and safety of FMT for the treatment of patients with CD-associated diarrhea was made.<br><br>RESULTS: Twenty full-text case series, 15 case reports, and 1 randomized controlled study were included for the final analysis. Almost all patients treated with donors' fecal infusion experienced recurrent episodes of CD-associated diarrhea despite standard antibiotic treatment. Of a total of 536 patients treated, 467 (87%) experienced resolution of diarrhea. Diarrhea resolution rates varied according to the site of infusion: 81% in the stomach; 86% in the duodenum/jejunum; 93% in the cecum/ascending colon; and 84% in the distal colon. No severe adverse events were reported with the procedure.<br><br>CONCLUSIONS: FMT seems efficacious and safe for the treatment of recurrent CDI. Hospitals should encourage the development of fecal transplantation programs to improve therapy of local patients.}, }
@article {pmid24440929, year = {2014}, author = {Voigtländer, T and Wlecke, J and Negm, AA and Lenzen, H and Manns, MP and Lankisch, TO}, title = {Calprotectin in bile: a disease severity marker in patients with primary sclerosing cholangitis.}, journal = {Journal of clinical gastroenterology}, volume = {48}, number = {10}, pages = {866-869}, doi = {10.1097/MCG.0000000000000042}, pmid = {24440929}, issn = {1539-2031}, mesh = {Adult ; Aged ; Bile/*chemistry ; Bile Duct Neoplasms/diagnosis/etiology/metabolism ; Bile Ducts, Intrahepatic ; Biomarkers/analysis/blood ; Cholangiocarcinoma/diagnosis/etiology/metabolism ; Cholangitis, Sclerosing/complications/*diagnosis/metabolism ; Cholelithiasis/diagnosis/metabolism ; Cross-Sectional Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Leukocyte L1 Antigen Complex/*analysis/blood ; Male ; Middle Aged ; Predictive Value of Tests ; Severity of Illness Index ; }, abstract = {GOALS: Our aim was to evaluate the diagnostic potential of calprotectin in serum and bile of patients with primary sclerosing cholangitis (PSC).<br><br>BACKGROUND: PSC is a chronic cholestatic liver disease of unknown etiology. It is characterized by progressive inflammation and fibrosis of the bile ducts leading to biliary cirrhosis and eventually liver failure. Reliable markers for disease activity and severity are still lacking. Subunits of calprotectin, a fecal marker of inflammation in inflammatory bowel disease, have been recently identified in bile.<br><br>STUDY: Calprotectin was measured in patients with PSC (n=56), cholangiocarcinoma (CC) complicating PSC (CC/PSC) (n=13), CC (n=30), and bile duct stones in bile (n=38) and serum (n=73) by enzyme-linked immunosorbent assay in a cross-sectional study. PSC patients were categorized by the Mayo risk score (MRS) to characterize the disease severity.<br><br>RESULTS: Calprotectin is present in bile, and the median concentration was significantly higher in PSC patients (P<0.05). Stratification of PSC patients by MRS showed significantly elevated calprotectin levels in bile in the MRS-high group (P<0.05). Calprotectin and MRS correlated significantly (P<0.05). The presence or absence of inflammatory bowel disease in PSC patients did not alter calprotectin levels in bile. Serum AP and calprotectin in bile correlated significantly (P=0.013). No significant correlation was found for other liver-related parameters. In contrast, serum calprotectin levels were significantly higher in patients with CC, but there was no association with PSC or disease activity/severity.<br><br>CONCLUSIONS: Calprotectin in bile is a promising disease marker in patients with PSC with a potential prognostic value.}, }
@article {pmid24440222, year = {2014}, author = {Dutta, SK and Girotra, M and Garg, S and Dutta, A and von Rosenvinge, EC and Maddox, C and Song, Y and Bartlett, JG and Vinayek, R and Fricke, WF}, title = {Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile Infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {12}, number = {9}, pages = {1572-1576}, doi = {10.1016/j.cgh.2013.12.032}, pmid = {24440222}, issn = {1542-7714}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biodiversity ; Biological Therapy/*methods ; Biota ; Clostridium Infections/*therapy ; Diarrhea/*therapy ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Recurrence ; Sequence Analysis, DNA ; Treatment Outcome ; Young Adult ; }, abstract = {The prevalence of recurrent Clostridium difficile infection (RCDI) is increasing; fecal microbiota transplantation (FMT) is an effective therapy. However, there have been no studies of the efficacy of a single session of combined enteral and colonic FMT or characterizations of changes in the microbiota between donors and recipients. We performed a study of 27 patients with RCDI who were given a fixed volume of processed fecal filtrate via enteroscopy and colonoscopy in a single session. Patients were closely monitored, and fecal samples were collected from 2 patient-donor pairs for 16S rRNA analysis. All patients had reduced stool frequency, abdominal pain, white blood cell counts, and elimination of fecal C difficile toxin (P < .05). FMT increased microbial diversity, increasing proportions of Lachnospiraceae (phylum Firmicutes) and reducing proportions of Enterobacteriaceae. FMT was associated with marked changes in the composition of fecal microbiota in 2 patients with RCDI.}, }
@article {pmid24439901, year = {2014}, author = {Kim, YG and Udayanga, KG and Totsuka, N and Weinberg, JB and Núñez, G and Shibuya, A}, title = {Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE2.}, journal = {Cell host &amp; microbe}, volume = {15}, number = {1}, pages = {95-102}, pmid = {24439901}, issn = {1934-6069}, support = {R01 DK091191/DK/NIDDK NIH HHS/United States ; R01 AI083334/AI/NIAID NIH HHS/United States ; R01 DK095782/DK/NIDDK NIH HHS/United States ; R01DK091191/DK/NIDDK NIH HHS/United States ; R01AI083334/AI/NIAID NIH HHS/United States ; }, mesh = {Adoptive Transfer ; Ampicillin/adverse effects ; Animals ; Anti-Bacterial Agents/adverse effects ; Aspirin/pharmacology ; Candida/immunology ; Candidiasis/*immunology/microbiology/pathology ; Cefoperazone/adverse effects ; Celecoxib ; Clindamycin/adverse effects ; Cyclooxygenase Inhibitors/pharmacology ; Dinoprostone/antagonists &amp; inhibitors/*immunology/pharmacology ; Dysbiosis/chemically induced/immunology/microbiology/pathology ; Feces/microbiology ; Gastrointestinal Tract/*immunology/microbiology/pathology ; Inflammation/immunology/microbiology/pathology ; Lung/*immunology/microbiology/pathology ; Macrophage Activation/drug effects ; Macrophages, Alveolar/drug effects/*immunology/transplantation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pyrazoles/pharmacology ; Sulfonamides/pharmacology ; }, abstract = {Although imbalances in gut microbiota composition, or "dysbiosis," are associated with many diseases, the effects of gut dysbiosis on host systemic physiology are less well characterized. We report that gut dysbiosis induced by antibiotic (Abx) treatment promotes allergic airway inflammation by shifting macrophage polarization in the lung toward the alternatively activated M2 phenotype. Adoptive transfer of alveolar macrophages derived from Abx-treated mice was sufficient to increase allergic airway inflammation. Abx treatment resulted in the overgrowth of a commensal fungal Candida species in the gut and increased plasma concentrations of prostaglandin E2 (PGE2), which induced M2 macrophage polarization in the lung. Suppression of PGE2 synthesis by the cyclooxygenase inhibitors aspirin and celecoxib suppressed M2 macrophage polarization and decreased allergic airway inflammatory cell infiltration in Abx-treated mice. Thus, Abx treatment can cause overgrowth of particular fungal species in the gut and promote M2 macrophage activation at distant sites to influence systemic responses including allergic inflammation.}, }
@article {pmid24438664, year = {2014}, author = {Bourlioux, P}, title = {[Current view on gut microbiota].}, journal = {Annales pharmaceutiques francaises}, volume = {72}, number = {1}, pages = {15-21}, doi = {10.1016/j.pharma.2013.09.001}, pmid = {24438664}, issn = {0003-4509}, mesh = {Animals ; Bacterial Translocation ; Complementary Therapies ; Environmental Pollutants/pharmacokinetics ; Feces/microbiology ; Humans ; Inflammation/microbiology/therapy ; Intestines/embryology/growth &amp; development/*microbiology ; Mammals/microbiology ; *Microbiota ; Probiotics/therapeutic use ; Symbiosis ; Xenobiotics/pharmacokinetics ; }, abstract = {Gut microbiota is more and more important since metagenomic research have brought new knowledge on this topic especially for human health. Firstly, gut microbiota is a key element for our organism he lives in symbiosis with. Secondly, it interacts favorably with many physiological functions of our organism. Thirdly, at the opposite, it can be an active participant in intestinal pathologies linked to a dysbiosis mainly in chronic inflammatory bowel diseases like Crohn disease or ulcerative colitis but also in obesity, metabolic syndrome, and more prudently in autism and behavioral disorders. In order to keep a good health, it is essential to protect our gut microbiota as soon as our young age and maintain it healthy. Face to a more and more important number of publications for treating certain digestive diseases with fecal microbial transplantation, it needs to be very careful and recommend further studies in order to assess risks and define standardized protocols. Gut microbiota metabolic capacities towards xenobiotics need to be developed, and we must take an interest in the modifications they induce on medicinal molecules. On the other hand, it is essential to study the potent effects of pesticides and other pollutants on microbiota functions.}, }
@article {pmid24434240, year = {2014}, author = {Pérez-Gracia, MT and Suay, B and Mateos-Lindemann, ML}, title = {Hepatitis E: an emerging disease.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {22}, number = {}, pages = {40-59}, doi = {10.1016/j.meegid.2014.01.002}, pmid = {24434240}, issn = {1567-7257}, mesh = {Animals ; *Communicable Diseases, Emerging ; *Hepatitis E ; *Hepatitis E virus ; Humans ; Swine ; Zoonoses ; }, abstract = {Currently, the infection with the hepatitis E virus represents the most frequent cause for acute hepatitis and jaundice in the world. According to WHO estimations, around two billion people, representing one third of the world's population, live in endemic areas for HEV and, therefore, are at risk of infection. In developed countries, the circulation of the virus in both human and animal (swine, boar, deer) sewage has been confirmed; however, the incidence rate is low compared to that of developing countries where outbreaks of acute hepatitis transmitted via the fecal-oral route are originated, more frequently in the flooding season or after natural disasters, combined with deficient sanitary conditions. There are currently 4 known genotypes of HEV. Genotypes 1 and 2 are isolated in all human epidemic outbreaks in developing countries, while genotypes 3 and 4 are isolated not only in humans but also in animals, in both developing and industrialized countries. These data support genotypes 3 and 4 having zoonotic nature. The diagnosis of this disease is based in the detection of anti-HEV IgG and IgM in blood serum using enzyme-linked immunosorbent methods. However, the method that best confirms the diagnosis is the RT-PCR, which detects HEV RNA in blood serum and also provides the genotype. The clinical course is generally that of an acute hepatitis which in some cases may require hospitalization and that, in transplant patients or HIV infected individuals can become a chronic hepatitis. Furthermore, the virus constitutes an important risk for pregnant women. The hepatitis E can present a wide range of symptoms, from a subclinical case to chronic liver disease with extrahepatic manifestations. For this reason, the diagnostic is challenging if no differential diagnosis is included. There is no specific antiviral drug for hepatitis E, but satisfactory results have been observed in some patients treated with pegylated interferon alfa2a and/or ribavirin. This revision is an update of all the molecular, epidemiological, clinic and preventive knowledge on this emergent disease up to date.}, }
@article {pmid24433460, year = {2014}, author = {Friedman-Moraco, RJ and Mehta, AK and Lyon, GM and Kraft, CS}, title = {Fecal microbiota transplantation for refractory Clostridium difficile colitis in solid organ transplant recipients.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {14}, number = {2}, pages = {477-480}, pmid = {24433460}, issn = {1600-6143}, support = {KL2 TR000455/TR/NCATS NIH HHS/United States ; UL1 TR000454/TR/NCATS NIH HHS/United States ; UL1TR000454/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; Clostridioides difficile/pathogenicity ; Clostridium Infections/etiology/*therapy ; Colitis/etiology/*therapy ; Diarrhea/etiology/therapy ; *Drug Resistance, Multiple, Bacterial ; Feces/*cytology/microbiology ; Female ; Humans ; Kidney Transplantation/*adverse effects ; Lung Transplantation/*adverse effects ; *Microbiota ; Prognosis ; Recurrence ; Transplant Recipients ; }, abstract = {Fecal microbiota transplantation (FMT) has been shown to be safe and efficacious in individuals with refractory Clostridium difficile. It has not been widely studied in individuals with immunosuppression due to concerns about infectious complications. We describe two solid organ transplant recipients, one lung and one renal, in this case report that both had resolution of their diarrhea caused by C. difficile after FMT. Both recipients required two FMTs to achieve resolution of their symptoms and neither had infectious complications. Immunosuppressed individuals are at high risk for acquisition of C. difficile and close monitoring for infectious complications after FMT is necessary, but should not preclude its use in patients with refractory disease due to C. difficile. Sequential FMT may be used to achieve cure in these patients with damaged microbiota from antibiotic use and immunosuppression.}, }
@article {pmid24426364, year = {2013}, author = {Gokce, M and Tuncer, M and Cetin, M and Gumruk, F}, title = {Molecular diagnosis of shwachman-diamond syndrome presenting with pancytopenia at an early age: the first report from Turkey.}, journal = {Indian journal of hematology &amp; blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion}, volume = {29}, number = {3}, pages = {161-163}, pmid = {24426364}, issn = {0971-4502}, abstract = {A three-month-old boy presented with growth failure, skeletal abnormalities, otitis media and pancytopenia. Exocrine pancreatic insufficiency was confirmed by low levels of fecal elastase. He was diagnosed as Shwachman-Diamond syndrome by clinical and laboratory findings. The diagnosis was confirmed by sequence analysis for SBDS gene on chromosome seven revealing compound heterozygous mutation, which are c.258+2T-C and c.183-184TA-CT. Matched unrelated donor screening for hematopoietic stem cell transplantation was initiated. Unfortunately, he died of respiratory difficulty at 5 months of age. Our case is the youngest patient whose presumptive Shwachman-Diamond syndrome diagnosis was confirmed by molecular analysis.}, }
@article {pmid24421790, year = {2013}, author = {Fearon, MA and Scalia, V and Huang, M and Dines, I and Ndao, M and Lagacé-Wiens, P}, title = {A case of vertical transmission of Chagas disease contracted via blood transfusion in Canada.}, journal = {The Canadian journal of infectious diseases &amp; medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale}, volume = {24}, number = {1}, pages = {32-34}, pmid = {24421790}, issn = {1712-9532}, abstract = {Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and is endemic in many countries in Latin America, where infected bugs of the Triatominea subfamily carry the parasite in the gut and transmit it to humans through fecal contamination of a bite. However, vertical transmission and transmission through blood transfusion and organ transplantation is well documented. Increasing immigration from endemic countries to North America has prompted blood operators, including Canadian Blood Services and Hema Quebec, to initiate blood donor testing for Chagas antibody. In the present report, an unusual case of vertical transmission from a mother, most likely infected through blood transfusion, and detected as part of a concurrent seroprevalence study in blood donors is described.}, }
@article {pmid24421645, year = {2013}, author = {Pathak, R and Enuh, HA and Patel, A and Wickremesinghe, P}, title = {Treatment of relapsing Clostridium difficile infection using fecal microbiota transplantation.}, journal = {Clinical and experimental gastroenterology}, volume = {7}, number = {}, pages = {1-6}, pmid = {24421645}, issn = {1178-7023}, abstract = {BACKGROUND: Clostridium difficile infection (CDI) has become a global concern over the last decade. In the United States, CDI escalated in incidence from 1996 to 2005 from 31 to 64/100,000. In 2010, there were 500,000 cases of CDI with an estimated mortality up to 20,000 cases a year. The significance of this problem is evident from the hospital costs of over 3 billion dollars annually. Fecal microbiota transplant (FMT) was first described in 1958 and since then about 500 cases have been published in literature in various small series and case reports. This procedure has been reported mainly from centers outside of the United States and acceptance of the practice has been difficult. Recently the US Food and Drug Administration (FDA) labeled FMT as a biological drug; as a result, guidelines will soon be required to help establish it as a mainstream treatment. More US experience needs to be reported to popularize this procedure here and form guidelines.<br><br>METHOD: We did a retrospective review of our series of patients with relapsing CDI who were treated with FMT over a 3-year period. We present our experience with FMT at a community hospital as a retrospective review and describe our procedure.<br><br>RESULTS: There were a total of 12 patients who underwent FMT for relapsing C. difficile. Only one patient failed to respond and required a second FMT. There were no complications associated with the transplant and all patients had resolution of symptoms within 48 hours of FMT.<br><br>CONCLUSION: FMT is a cheap, easily available, effective therapy for recurrent CDI; it can be safely performed in a community hospital setting with similar results.}, }
@article {pmid24412527, year = {2014}, author = {Petrof, EO and Khoruts, A}, title = {From stool transplants to next-generation microbiota therapeutics.}, journal = {Gastroenterology}, volume = {146}, number = {6}, pages = {1573-1582}, pmid = {24412527}, issn = {1528-0012}, support = {R21 AI091907/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Biological Therapy/*methods ; Clostridioides difficile/*growth &amp; development/pathogenicity ; Dysbiosis ; Enterocolitis, Pseudomembranous/epidemiology/microbiology/*therapy ; Epidemics ; Feces/*microbiology ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology ; *Microbiota ; Recurrence ; Risk Factors ; Treatment Outcome ; }, abstract = {The epidemic of Clostridium difficile infection fueled by new virulent strains of the organism has led to increased use of fecal microbiota transplantation (FMT). The procedure is effective for even the most desperate cases after failure of multiple courses of antibiotics. The approach recognizes microbiota to be integral to normal human physiology, and microbiota being used in FMT represents a new class of therapeutics. Imbalance in the composition and altered activity of the microbiota are associated with many diseases. Consequently, there is growing interest in applying FMT to non-C difficile indications. However, this may succeed only if microbiota therapeutics are developed systematically, based on mechanistic understanding, and applying up-to-date principles of microbial ecology. We discuss 2 pathways in the development of this new therapeutic class: whole microbial communities separated from donor stool and an assembly of specific fecal microorganisms grown in vitro.}, }
@article {pmid24410618, year = {2014}, author = {Rineh, A and Kelso, MJ and Vatansever, F and Tegos, GP and Hamblin, MR}, title = {Clostridium difficile infection: molecular pathogenesis and novel therapeutics.}, journal = {Expert review of anti-infective therapy}, volume = {12}, number = {1}, pages = {131-150}, pmid = {24410618}, issn = {1744-8336}, support = {R01 AI050875/AI/NIAID NIH HHS/United States ; R01AI050875/AI/NIAID NIH HHS/United States ; }, mesh = {Clostridioides difficile/*drug effects/metabolism/pathogenicity ; Drug Resistance, Bacterial ; Enterocolitis, Pseudomembranous/immunology/pathology/*therapy ; Humans ; Spores, Bacterial/physiology ; Virulence ; }, abstract = {The Gram-positive anaerobic bacterium Clostridium difficile produces toxins A and B, which can cause a spectrum of diseases from pseudomembranous colitis to C. difficile-associated diarrhea. A limited number of C. difficile strains also produce a binary toxin that exhibits ADP ribosyltransferase activity. Here, the structure and the mechanism of action of these toxins as well as their role in disease are reviewed. Nosocomial C. difficile infection is often contracted in hospital when patients treated with antibiotics suffer a disturbance in normal gut microflora. C. difficile spores can persist on dry, inanimate surface for months. Metronidazole and oral vancomycin are clinically used for treatment of C. difficile infection but clinical failure and concern about promotion of resistance are motivating the search for novel non-antibiotic therapeutics. Methods for controlling both toxins and spores, replacing gut microflora by probiotics or fecal transplant, and killing bacteria in the anaerobic gut by photodynamic therapy are discussed.}, }
@article {pmid24402367, year = {2014}, author = {Montassier, E and Batard, E and Massart, S and Gastinne, T and Carton, T and Caillon, J and Le Fresne, S and Caroff, N and Hardouin, JB and Moreau, P and Potel, G and Le Vacon, F and de La Cochetière, MF}, title = {16S rRNA gene pyrosequencing reveals shift in patient faecal microbiota during high-dose chemotherapy as conditioning regimen for bone marrow transplantation.}, journal = {Microbial ecology}, volume = {67}, number = {3}, pages = {690-699}, pmid = {24402367}, issn = {1432-184X}, mesh = {Adult ; Antineoplastic Agents/*therapeutic use ; Bacteria/*drug effects/*genetics/isolation &amp; purification ; *Bone Marrow Transplantation ; Chromatography, High Pressure Liquid ; DNA, Bacterial/*genetics/isolation &amp; purification ; Denaturing Gradient Gel Electrophoresis ; Feces/*microbiology ; Female ; France ; High-Throughput Nucleotide Sequencing ; Humans ; Lymphoma, Non-Hodgkin/drug therapy/*therapy ; Male ; Microbiota/*drug effects ; Middle Aged ; Molecular Sequence Data ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, RNA ; }, abstract = {Gastrointestinal disturbances are a side-effect frequently associated with haematological malignancies due to the intensive cytotoxic treatment given in connection with bone marrow transplantation (BMT). However, intestinal microbiota changes during chemotherapy remain poorly described, probably due to the use of culture-based and low-resolution molecular methods in previous studies. The objective of our study was to apply a next generation DNA sequencing technology to analyse chemotherapy-induced changes in faecal microbiota. We included eight patients with non-Hodgkin's lymphoma undergoing one course of BMT conditioning chemotherapy. We collected a prechemotherapy faecal sample, the day before chemotherapy was initiated, and a postchemotherapy sample, collected 1 week after the initiation of chemotherapy. Total DNA was extracted from faecal samples, denaturing high-performance liquid chromatography based on amplification of the V6 to V8 region of the 16S ribosomal RNA (rRNA) gene, and 454-pyrosequencing of the 16 S rRNA gene, using PCR primers targeting the V5 and V6 hypervariable 16S rRNA gene regions were performed. Raw sequence data were screened, trimmed, and filtered using the QIIME pipeline. We observed a steep reduction in alpha diversity and significant differences in the composition of the intestinal microbiota in response to chemotherapy. Chemotherapy was associated with a drastic drop in Faecalibacterium and accompanied by an increase of Escherichia. The chemotherapy-induced shift in the intestinal microbiota could induce severe side effects in immunocompromised cancer patients. Our study is a first step in identifying patients at risk for gastrointestinal disturbances and to promote strategies to prevent this drastic shift in intestinal microbiota.}, }
@article {pmid24399213, year = {2015}, author = {Vandenplas, Y and Veereman, G and van der Werff Ten Bosch, J and Goossens, A and Pierard, D and Samsom, JN and Escher, JC}, title = {Fecal Microbial Transplantation in Early-Onset Colitis: Caution Advised.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {61}, number = {3}, pages = {e12-4}, doi = {10.1097/MPG.0000000000000281}, pmid = {24399213}, issn = {1536-4801}, mesh = {Colitis, Ulcerative/genetics/microbiology/*surgery ; Fecal Microbiota Transplantation/*adverse effects/methods ; Female ; Humans ; Infant ; }, }
@article {pmid24399149, year = {2014}, author = {Pamer, EG}, title = {Fecal microbiota transplantation: effectiveness, complexities, and lingering concerns.}, journal = {Mucosal immunology}, volume = {7}, number = {2}, pages = {210-214}, pmid = {24399149}, issn = {1935-3456}, support = {AI042135/AI/NIAID NIH HHS/United States ; AI095706/AI/NIAID NIH HHS/United States ; CA023766/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Feces/*microbiology ; Gastrointestinal Tract/immunology/*microbiology ; Humans ; Intestinal Diseases/immunology/*microbiology/*therapy ; *Microbiota ; }, abstract = {The mammalian colon is home to a microbial ecosystem that enhances resistance to infection, stimulates mucosal immune defenses, synthesizes essential vitamins, and promotes caloric uptake by hydrolyzing complex carbohydrates. The bacterial populations inhabiting the gut are complex and vary between different individuals. Clinical and experimental studies reveal that the colonic microbiota can enhance or ameliorate intestinal and systemic inflammatory diseases. Because of its potential to enhance resistance to infection and to reduce inflammatory diseases, targeted manipulation of microbial populations is a growing focus of investigation. The most dramatic manipulation of the intestinal microbiota involves fecal microbiota transplantation (FMT) from healthy donors to individuals with specific diseases. Remarkable clinical effectiveness of FMT has been demonstrated for recurrent Clostridium difficile infection and ongoing studies are investigating FMT for other diseases. Transplantation of complex microbial populations to recipients likely triggers mucosal immune responses that, depending on the microbiota composition and the recipient's genotype, could range from pro- to anti-inflammatory. The impact of FMT on the recipient immune system is complex and unpredictable. Ongoing discovery of commensal microbes and investigations of their impact on the host will lead to the development of new probiotic agents and microbial consortia that will eventually replace FMT.}, }
@article {pmid24397146, year = {2013}, author = {Salonen, A}, title = {[Human microbiomes--normal microbiota underlying a growing number of diseases].}, journal = {Duodecim; laaketieteellinen aikakauskirja}, volume = {129}, number = {22}, pages = {2341-2348}, pmid = {24397146}, issn = {0012-7183}, mesh = {Bacterial Infections/*microbiology ; Feces/microbiology ; Humans ; Microbiota/*physiology ; Skin/microbiology ; }, abstract = {Human microbiomes refer to complex bacterial communities colonizing the skin and the mucous membranes of various body cavities. Microbiomes and especially their aberrations have recently been linked to numerous local and systemic diseases. Identification of factors regulating the composition and function of microbiomes is therefore medically highly relevant, but still in its infancy. With the exception of fecal transplantation, microbiome-based medical applications do not yet exist. The active research in the field is expected to provide better understanding on the role of microbiomes in human health, and enable their clinical utilization in the future.}, }
@article {pmid24388329, year = {2014}, author = {Myers, KC and Bolyard, AA and Otto, B and Wong, TE and Jones, AT and Harris, RE and Davies, SM and Dale, DC and Shimamura, A}, title = {Variable clinical presentation of Shwachman-Diamond syndrome: update from the North American Shwachman-Diamond Syndrome Registry.}, journal = {The Journal of pediatrics}, volume = {164}, number = {4}, pages = {866-870}, pmid = {24388329}, issn = {1097-6833}, support = {5 R24 AI049363-09/AI/NIAID NIH HHS/United States ; R24 AI049393/AI/NIAID NIH HHS/United States ; K12 HD028827/HD/NICHD NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; R01 HL079582/HL/NHLBI NIH HHS/United States ; 5 R01 HL079582-11/HL/NHLBI NIH HHS/United States ; R03 AI079734/AI/NIAID NIH HHS/United States ; 1 R03 AI079734-02/AI/NIAID NIH HHS/United States ; P30 DK090971/DK/NIDDK NIH HHS/United States ; UL1 TR000077/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Bone Marrow Diseases/*diagnosis ; Child ; Child, Preschool ; Exocrine Pancreatic Insufficiency/*diagnosis ; Female ; Humans ; Infant ; Lipomatosis/*diagnosis ; Male ; North America ; Registries ; Retrospective Studies ; Shwachman-Diamond Syndrome ; }, abstract = {OBJECTIVES: To investigate the range of clinical presentations for Shwachman-Diamond syndrome (SDS) with the long-term goal of improving diagnosis.<br><br>STUDY DESIGN: We reviewed the North American Shwachman-Diamond Syndrome Registry. Genetic reports of biallelic Shwachman-Bodian-Diamond syndrome mutations confirming the diagnosis of SDS were available for 37 patients.<br><br>RESULTS: Neutropenia was the most common hematologic abnormality at presentation (30/37, 81%); however, only 51% (19/37) of patients presented with the classic combination of neutropenia and steatorrhea. Absence of pancreatic lipomatosis on ultrasound or computed tomography scan, normal fecal elastase levels, and normal skeletal survey do not rule out the diagnosis of SDS. SDS was diagnosed in 2 asymptomatic siblings of SDS probands. Twenty-four of 37 patients (65%) had congenital anomalies.<br><br>CONCLUSION: Our cohort reveals a broad range of clinical presentation for SDS. Clues to the underlying diagnosis of SDS included cytopenias with a hypocellular marrow, congenital anomalies, family history, and myelodysplasia with clonal abnormalities frequently found in SDS. Reliance on classic clinical criteria for SDS would miss or delay diagnosis of a significant subset of patients with SDS.}, }
@article {pmid24388028, year = {2014}, author = {Khanna, S and Tosh, PK}, title = {A clinician's primer on the role of the microbiome in human health and disease.}, journal = {Mayo Clinic proceedings}, volume = {89}, number = {1}, pages = {107-114}, doi = {10.1016/j.mayocp.2013.10.011}, pmid = {24388028}, issn = {1942-5546}, mesh = {Animals ; Autoimmune Diseases/*microbiology ; Causality ; Clinical Medicine/education ; Clostridioides difficile ; Clostridium Infections/*microbiology ; Comorbidity ; Curriculum ; Drug Resistance, Multiple ; Humans ; Hypersensitivity/*microbiology ; Inflammatory Bowel Diseases/*microbiology ; Intestinal Diseases/*microbiology ; *Microbiota ; Neuropsychiatry ; Obesity/*microbiology ; United States ; }, abstract = {The importance of the commensal microbiota that colonizes the skin, gut, and mucosal surfaces of the human body is being increasingly recognized through a rapidly expanding body of science studying the human microbiome. Although, at first glance, these discoveries may seem esoteric, the clinical implications of the microbiome in human health and disease are becoming clear. As such, it will soon be important for practicing clinicians to have an understanding of the basic concepts of the human microbiome and its relation to human health and disease. In this Concise Review, we provide a brief introduction to clinicians of the concepts underlying this burgeoning scientific field and briefly explore specific disease states for which the potential role of the human microbiome is becoming increasingly evident, including Clostridium difficile infection, inflammatory bowel disease, colonization with multidrug-resistant organisms, obesity, allergic diseases, autoimmune diseases, and neuropsychiatric illnesses, and we also discuss current and future roles of microbiome restorative therapies.}, }
@article {pmid24380986, year = {2014}, author = {Altomare, DF and Bonfrate, L and Krawczyk, M and Lammert, F and Caputi-Jambrenghi, O and Rizzi, S and Vacca, M and Portincasa, P}, title = {The inulin hydrogen breath test predicts the quality of colonic preparation.}, journal = {Surgical endoscopy}, volume = {28}, number = {5}, pages = {1579-1587}, pmid = {24380986}, issn = {1432-2218}, mesh = {Breath Tests/methods ; Colon/drug effects/metabolism ; Colonoscopy/*standards ; Colorectal Neoplasms/*diagnosis ; Female ; Follow-Up Studies ; Humans ; Hydrogen/*analysis ; Inulin/*analysis ; Male ; Middle Aged ; Polyethylene Glycols/*pharmacology ; Predictive Value of Tests ; Prospective Studies ; *Respiration ; Surface-Active Agents/pharmacology ; }, abstract = {BACKGROUND: Successful bowel preparation is essential to an adequate performance of colonoscopy. Polyethylene glycol (PEG) with electrolyte solutions induces diarrhea with depletion of substrates fermentable by hydrogen (H2)-producing colonic microbiota. Inulin has recently been suggested as a prebiotic substrate for the H2 breath test because it is resistant to intestinal hydrolysis and is fermented mostly by the colonic bacteria. This study aimed to assess time-dependent changes in H2 breath levels in order to predict the colonic preparation of patients scheduled for colonoscopy with or without oral supplementation of inulin.<br><br>METHODS: In this prospective nonrandomized trial, 127 subjects drank 4 l of PEG 280-mg solution as bowel preparation for colonoscopy. A subgroup of 31 patients also ingested inulin (10 g in 200 ml of water) at breakfast as an additional substrate to increase colonic H2 production. Measurements of H2 breath levels were performed immediately before and after colonic preparation. As the main outcome measure, the quality of the colonic preparation was scored as excellent to fair (i.e., clean bowel allowing successful pan-colonoscopy, including the terminal ileum) or poor (incomplete colonoscopy due to fecal debris).<br><br>RESULTS: The H2 breath levels decreased from 11.0 &#xb1; 1.8 ppm before PEG to 1.8 &#xb1; 0.3 ppm after PEG (n = 18; P < 0.001). The H2 concentrations after PEG ingestion were significantly lower (P < 0.001) in the patients with excellent-to-fair preparation than in the 19 patients with poor preparation. Ingestion of inulin induced an overall increase in H2 breath levels and improved discrimination between the patients with excellent-to-fair colonic preparation and those with poor preparation, leading to the sensitivity and specificity of such a test reaching 100 %.<br><br>CONCLUSIONS: The H2 breath test with inulin ingestion can be a simple, noninvasive, reliable method for predicting successful colonic preparation that leads to cost savings and less patient discomfort/stress or need to repeat colonoscopy.}, }
@article {pmid24372725, year = {2014}, author = {Dodin, M and Katz, DE}, title = {Faecal microbiota transplantation for Clostridium difficile infection.}, journal = {International journal of clinical practice}, volume = {68}, number = {3}, pages = {363-368}, doi = {10.1111/ijcp.12320}, pmid = {24372725}, issn = {1742-1241}, mesh = {Attitude to Health ; Biological Therapy/*methods/psychology ; *Clostridioides difficile ; Clostridium Infections/psychology/*therapy ; Colon/microbiology ; Donor Selection ; Feces/*microbiology ; Humans ; *Microbiota ; }, abstract = {PURPOSE: To review the current clinical literature regarding the use of fecal microbiota transplantation (FMT) for severe and recurrent Clostridium difficile disease (CDAD).<br><br>BACKGROUND: Clostridium difficile (C. difficile) is a gram positive, spore forming bacteria, and an important nosocomial pathogen causing healthcare associated diarrhoea in hospitalized patients in developed and developing countries. During the past several years, CDAD has become more frequent, severe, refractory, and more likely to relapse. It has become apparent that C. difficile is no longer just a nosocomial infection, with a rising rate of infection in populations not previously affected. Standard treatment regimens and new medications exist, but recurrence rates are high.<br><br>METHODS: Using PubMed, we conducted a Boolean search with the following medical subject headings (MeSH): Clostridium difficile infection and fecal transplantation or recurrent C. difficile infection. We restricted the search to human studies, published in English, between 2011 through June 1, 2013.<br><br>RESULTS: There were 104 publications identified. Of those related to FMT, there were 20 clinical reviews, 6 case reports, 3 clinical trials (one, a randomized control trial), and 1 meta-analysis. Since 1958 there have been 36 published reports of FMT for C. difficile infection (CDI) representing 583 patients. Success rates were higher when FMT was administered via colonoscopy (representing the majority of patients, 79.2%). The overall success rate for FMT, regardless of administration method, was 80-98%.<br><br>CONCLUSION: Fecal microbiota transplantation attempts to restore the normal microbiome of the colon, and has achieved a cure rate reaching more than 90%. Mounting evidence supports the utility of FMT for severe and recurrent cases of CDI. Barriers that will need to be addressed are patient perceptions and fears, standard protocol development, and further clinical trials.}, }
@article {pmid24368622, year = {2014}, author = {Moore, T and Rodriguez, A and Bakken, JS}, title = {Fecal microbiota transplantation: a practical update for the infectious disease specialist.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {58}, number = {4}, pages = {541-545}, doi = {10.1093/cid/cit950}, pmid = {24368622}, issn = {1537-6591}, mesh = {Biological Therapy/*methods ; Drugs, Investigational/*therapeutic use ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; *Investigational New Drug Application ; United States ; }, abstract = {Fecal microbiota transplantation (FMT) has been shown to be a superior therapeutic modality for the treatment of recurrent Clostridium difficile infection (RCDI). Recently the US Food and Drug Administration (FDA) determined that human stool should be classified as a biological agent and its use should be regulated to ensure patient safety. Consequently, the FDA determined that prescribers of FMT must possess an approved investigational new drug (IND) permit to administer FMT for the purpose of conducting research or treating any gastrointestinal condition other than RCDI. Although an IND is not required for use of FMT to treat RCDI, an IND is strongly encouraged and may ultimately be required. This article provides step-by-step guidance to infectious disease specialists on how to navigate the regulatory requirements and successfully obtain an IND before they can begin to use FMT as part of their clinical practice.}, }
@article {pmid24354958, year = {2014}, author = {Emanuelsson, F and Claesson, BE and Ljungström, L and Tvede, M and Ung, KA}, title = {Faecal microbiota transplantation and bacteriotherapy for recurrent Clostridium difficile infection: a retrospective evaluation of 31 patients.}, journal = {Scandinavian journal of infectious diseases}, volume = {46}, number = {2}, pages = {89-97}, doi = {10.3109/00365548.2013.858181}, pmid = {24354958}, issn = {1651-1980}, mesh = {Adult ; Aged ; Biological Therapy/*methods ; Clostridium Infections/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; *Secondary Prevention ; Treatment Outcome ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (CDI) is a significant problem due to its increased incidence and severity. Failure rates for standard antibiotic therapies are high. In our hospital, faecal microbiota transplantation (FMT), or instillation of a culture mixture of known enteric bacteria in saline as rectal bacteriotherapy (RBT), has long been used as 'rescue therapy' in patients with recurrent disease, in whom repeated courses of standard antibiotic treatment have failed. We wanted to evaluate the effectiveness of FMT and RBT for recurrent CDI.<br><br>METHODS: The records of 31 patients treated with either FMT or RBT for recurrent CDI were reviewed retrospectively. FMT was based on faecal donation by a close relative and RBT on a defined saline mixture of 10 individually cultured enteric bacterial strains originally isolated from healthy persons. Both types of instillation were carried out through a rectal catheter. FMT (500 ml) was given as 1 installation. RBT (200 ml) was given as 2 or 3 installations with an interval of 2 days between courses. Treatment success was defined as a sustained loss of symptoms and discontinuation of diarrhoea within 3 days.<br><br>RESULTS: Of 31 patients, 23 (74%) responded successfully to the treatment: 16 of 23 (70%) receiving FMT and 7 of 8 (88%) receiving RBT.<br><br>CONCLUSION: We found FMT to be effective in patients with recurrent CDI. RBT based on a predefined bacterial suspension was as effective as or better than FMT based on faecal donation; however, multiple installations may be needed.}, }
@article {pmid24338758, year = {2013}, author = {Gross, M and Meyer, C}, title = {[Stool transplantation for relapsing Cl. difficile colitis].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {51}, number = {12}, pages = {1441-1443}, doi = {10.1055/s-0033-1350583}, pmid = {24338758}, issn = {1439-7803}, mesh = {Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile ; Diarrhea/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Vancomycin/*therapeutic use ; }, }
@article {pmid24337835, year = {2014}, author = {Hirschburger, M and Schwandner, T and Hecker, A and Kierer, W and Weinel, R and Padberg, W}, title = {Fistulectomy with primary sphincter reconstruction in the treatment of high transsphincteric anal fistulas.}, journal = {International journal of colorectal disease}, volume = {29}, number = {2}, pages = {247-252}, pmid = {24337835}, issn = {1432-1262}, mesh = {Adult ; Aged ; Anal Canal/*pathology/*surgery ; Demography ; Fecal Incontinence/etiology ; Female ; Humans ; Male ; Middle Aged ; Postoperative Care ; Postoperative Complications/etiology ; Quality of Life ; Plastic Surgery Procedures/*methods ; Rectal Fistula/complications/*surgery ; }, abstract = {PURPOSE: The treatment of transsphincteric anal fistulas is a challenge between recurrence rate and incontinence. Many surgical and conservative procedures have been described in the treatment of anal fistulas. Fistulectomy and primary sphincter reconstruction (FPSR) has not gained great popularity in this field due to the risk of sphincter damage. The aim of this study is to evaluate FPSR in the treatment of transsphincteric fistulas.<br><br>METHODS: We retrospectively analyzed 50 patients with high transsphincteric fistulas of cryptoglandular origin that were treated with FPSR between 2005 and 2008. Preoperative assessment included physical and proctologic examination. Continence and pain scores were evaluated preoperatively and postoperatively.<br><br>RESULTS: In our 50 patients, 22 patients (44&#xa0;%) had a previous proctologic operation and 11 patients (22&#xa0;%) presented with recurrent fistulas. The fistulas existed for an average of 8&#xa0;months. The operation time was 28&#x2009;&#xb1;&#x2009;16&#xa0;min. Mean follow-up was 22&#xb1; months. The fistula healed in 44 patients (88&#xa0;%) who developed no recurrence. In five patients (10&#xa0;%), the fistula healed, but they developed a recurrence in the observation period. In one patient (2&#xa0;%), the fistula did not heal. Three patients developed low-grade incontinence for flatus, and one patient with 2&#xb0; incontinence improved. Preoperatively and postoperatively calculated continence and pain scores showed a slight but significant elevation in the Clinical Continence Score, the German Society of Coloproctology Score showed no significant difference, and preexisting pain was reduced significantly by surgery.<br><br>CONCLUSIONS: FPSR is a safe surgical procedure for the treatment of high transsphincteric anal fistula. The primary healing rate is high with a low risk of recurrence or incontinence.}, }
@article {pmid24335204, year = {2013}, author = {Broecker, F and Kube, M and Klumpp, J and Schuppler, M and Biedermann, L and Hecht, J and Hombach, M and Keller, PM and Rogler, G and Moelling, K}, title = {Analysis of the intestinal microbiome of a recovered Clostridium difficile patient after fecal transplantation.}, journal = {Digestion}, volume = {88}, number = {4}, pages = {243-251}, doi = {10.1159/000355955}, pmid = {24335204}, issn = {1421-9867}, mesh = {Biological Therapy ; *Clostridioides difficile ; DNA, Bacterial/*analysis ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Intestines/*microbiology ; Metagenomics ; *Microbiota ; Middle Aged ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Clostridium difficile infections upon antibiotic disruption of the gut microbiota are potentially lethal. Fecal microbiota transplantation (FMT) is a promising treatment option for recurrent C. difficile-associated disease (CDAD). Here, we present a patient with recurrent CDAD that received FMT, leading to full recovery for what has now been 3 years. We performed metagenomic sequencing on stool samples to assess if there are indications for recolonization with C. difficile and changes in the gut microbiota after FMT.<br><br>METHODS: DNA from the stool of the donor and recipient was subjected to illumina sequencing. Obtained read sets were assembled to contiguous sequences and open reading frames were predicted. Deduced proteins were taxonomically assigned.<br><br>RESULTS: We detected complex and apparently healthy microbiomes in the donor's and recipient's intestines after FMT, but no indications for C. difficile colonization.<br><br>CONCLUSIONS: Metagenomic analysis proved suitable to analyze the intestinal microbiome after FMT. Discussion of our evaluation procedure and data management may be helpful for future studies. We demonstrated restoration of a healthy and diverse gut microbiome with chimeric composition from donor and recipient, and long-lasting clearance of C. difficile. The procedure is simple, cheap, caused no side effects, and was stable over 3 years.}, }
@article {pmid24334794, year = {2014}, author = {Lofgren, ET and Moehring, RW and Anderson, DJ and Weber, DJ and Fefferman, NH}, title = {A mathematical model to evaluate the routine use of fecal microbiota transplantation to prevent incident and recurrent Clostridium difficile infection.}, journal = {Infection control and hospital epidemiology}, volume = {35}, number = {1}, pages = {18-27}, pmid = {24334794}, issn = {1559-6834}, support = {K23 AI095357/AI/NIAID NIH HHS/United States ; T32 AI070114/AI/NIAID NIH HHS/United States ; UL1 RR025747/RR/NCRR NIH HHS/United States ; UL1RR025747/RR/NCRR NIH HHS/United States ; }, mesh = {*Biological Therapy ; Carrier State/microbiology/transmission ; *Clostridioides difficile ; Computer Simulation ; Enterocolitis, Pseudomembranous/*prevention &amp; control/transmission ; Feces/*microbiology ; Humans ; Intensive Care Units ; Intestines/*microbiology ; Mathematical Concepts ; *Models, Biological ; Prospective Studies ; Secondary Prevention ; Southeastern United States ; }, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) has been suggested as a new treatment to manage Clostridium difficile infection (CDI). With use of a mathematical model of C. difficile within an intensive care unit (ICU), we examined the potential impact of routine FMT.<br><br>DESIGN, SETTING, AND PATIENTS: A mathematical model of C. difficile transmission, supplemented with prospective cohort, surveillance, and billing data from hospitals in the southeastern United States.<br><br>METHODS: Cohort, surveillance, and billing data as well as data from the literature were used to construct a compartmental model of CDI within an ICU. Patients were defined as being in 1 of 6 potential health states: uncolonized and at low risk; uncolonized and at high risk; colonized and at low risk; colonized and at high risk; having CDI; or treated with FMT.<br><br>RESULTS: The use of FMT to treat patients after CDI was associated with a statistically significant reduction in recurrence but not with a reduction in incident cases. Treatment after administration of high-risk medications, such as antibiotics, did not result in a decrease in recurrence but did result in a statistically significant difference in incident cases across treatment groups, although whether this difference was clinically relevant was questionable.<br><br>CONCLUSIONS: Our study is a novel mathematical model that examines the effect of FMT on the prevention of recurrent and incident CDI. The routine use of FMT represents a promising approach to reduce complex recurrent cases, but a reduction in CDI incidence will require the use of other methods to prevent transmission.}, }
@article {pmid24330161, year = {2014}, author = {Bert, F and Larroque, B and Dondero, F and Durand, F and Paugam-Burtz, C and Belghiti, J and Moreau, R and Nicolas-Chanoine, MH}, title = {Risk factors associated with preoperative fecal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae in liver transplant recipients.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {16}, number = {1}, pages = {84-89}, doi = {10.1111/tid.12169}, pmid = {24330161}, issn = {1399-3062}, mesh = {Adult ; Amikacin ; Cefoxitin ; Ciprofloxacin ; Drug Resistance, Bacterial ; End Stage Liver Disease/complications/*surgery ; Enterobacter cloacae/isolation &amp; purification/physiology ; Enterobacteriaceae/*isolation &amp; purification/physiology ; Enterobacteriaceae Infections/complications/*microbiology ; Escherichia coli/isolation &amp; purification/physiology ; Escherichia coli Infections/complications/microbiology ; Feces/*microbiology ; Female ; Humans ; Imipenem ; Klebsiella/isolation &amp; purification/physiology ; Klebsiella Infections/complications/microbiology ; Klebsiella pneumoniae/isolation &amp; purification/physiology ; *Liver Transplantation ; Logistic Models ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Multivariate Analysis ; Penicillanic Acid/analogs &amp; derivatives ; Peritonitis ; Piperacillin ; Piperacillin, Tazobactam Drug Combination ; *Preoperative Period ; Risk Factors ; Severity of Illness Index ; beta-Lactamases/*metabolism ; *beta-Lactams ; }, abstract = {OBJECTIVE: The aim of the study was to identify risk factors associated with pre-transplant fecal carriage of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in liver transplant recipients.<br><br>PATIENTS AND METHODS: Over a 3-year period (January 2009-December 2011), 317 patients who underwent liver transplantation were screened preoperatively for fecal carriage of ESBL-producing Enterobacteriaceae. Risk factors for fecal carriage were investigated by univariate analysis and stepwise logistic regression.<br><br>RESULTS: Of the 317 patients screened, 50 (15.7%) harbored an ESBL-producing isolate. Previous infection with an ESBL-producing organism had developed during the last 6 months in 20% of fecal carriers versus in none of the non-carriers. Other variables associated with fecal carriage were a model for end-stage liver disease score &#x2265;25, pre-transplant stay in the intensive care unit &#x2265;48 h, hospital stay &#x2265;10 days in the last 6 months, a history of spontaneous bacterial peritonitis (SBP), exposure to a &#x3b2;-lactam agent in the last month, and prophylaxis with norfloxacin. Independent predictors of fecal carriage in the multivariate logistic regression model were exposure to a &#x3b2;-lactam agent in the month preceding transplantation (odds ratio [OR] = 7.8, confidence interval [CI] = 4-15.5, P < 0.001), and a history of SBP (OR = 2.4, CI = 1.1-4.9, P = 0.02).<br><br>CONCLUSIONS: Previous infection with an ESBL-producing isolate, recent exposure to a &#x3b2;-lactam agent, and a history of SBP are risk factors for preoperative fecal carriage of ESBL-producing Enterobacteriaceae in liver transplant recipients. Patients at risk of fecal carriage should receive intraoperative prophylaxis and, when necessary, empiric postoperative antimicrobial treatment that includes coverage for these organisms.}, }
@article {pmid24328373, year = {2014}, author = {Borody, TJ and Peattie, D and Kapur, A}, title = {Could fecal microbiota transplantation cure all Clostridium difficile infections?.}, journal = {Future microbiology}, volume = {9}, number = {1}, pages = {1-3}, doi = {10.2217/fmb.13.146}, pmid = {24328373}, issn = {1746-0921}, mesh = {Biological Therapy/adverse effects/*methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Feces/*microbiology ; Treatment Outcome ; }, }
@article {pmid24303043, year = {2013}, author = {Song, Y and Garg, S and Girotra, M and Maddox, C and von Rosenvinge, EC and Dutta, A and Dutta, S and Fricke, WF}, title = {Microbiota dynamics in patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {PloS one}, volume = {8}, number = {11}, pages = {e81330}, pmid = {24303043}, issn = {1932-6203}, mesh = {Aged ; Anti-Bacterial Agents/pharmacology ; Biodiversity ; Biological Therapy/*methods ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*microbiology/*therapy ; Feces/*microbiology ; Female ; Follow-Up Studies ; Humans ; Male ; Metagenome ; *Microbiota ; Middle Aged ; RNA, Ribosomal, 16S ; Treatment Outcome ; }, abstract = {Clostridium difficile causes antibiotic-associated diarrhea and pseudomembraneous colitis and is responsible for a large and increasing fraction of hospital-acquired infections. Fecal microbiota transplantation (FMT) is an alternate treatment option for recurrent C. difficile infection (RCDI) refractory to antibiotic therapy. It has recently been discussed favorably in the clinical and scientific communities and is receiving increasing public attention. However, short- and long-term health consequences of FMT remain a concern, as the effects of the transplanted microbiota on the patient remain unknown. To shed light on microbial events associated with RCDI and treatment by FMT, we performed fecal microbiota analysis by 16S rRNA gene amplicon pyrosequencing of 14 pairs of healthy donors and RCDI patients treated successfully by FMT. Post-FMT patient and healthy donor samples collected up to one year after FMT were studied longitudinally, including one post-FMT patient with antibiotic-associated relapse three months after FMT. This analysis allowed us not only to confirm prior reports that RCDI is associated with reduced diversity and compositional changes in the fecal microbiota, but also to characterize previously undocumented post-FMT microbiota dynamics. Members of the Streptococcaceae, Enterococcaceae, or Enterobacteriaceae were significantly increased and putative butyrate producers, such as Lachnospiraceae and Ruminococcaceae were significantly reduced in samples from RCDI patients before FMT as compared to post-FMT patient and healthy donor samples. RCDI patient samples showed more case-specific variations than post-FMT patient and healthy donor samples. However, none of the bacterial groups were invariably associated with RCDI or successful treatment by FMT. Overall microbiota compositions in post-FMT patients, specifically abundances of the above-mentioned Firmicutes, continued to change for at least 16 weeks after FMT, suggesting that full microbiota recovery from RCDI may take much longer than expected based on the disappearance of diarrheal symptoms immediately after FMT.}, }
@article {pmid24298986, year = {2013}, author = {Desoubeaux, G and Maakaroun-Vermesse, Z and Lier, C and Bailly, E and Morio, F and Labarthe, F and Bernard, L and Chandenier, J}, title = {Successful treatment with fumagillin of the first pediatric case of digestive microsporidiosis in a liver-kidney transplant.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {15}, number = {6}, pages = {E250-9}, doi = {10.1111/tid.12158}, pmid = {24298986}, issn = {1399-3062}, mesh = {Antifungal Agents/*therapeutic use ; Child ; Child, Preschool ; Cyclohexanes/*therapeutic use ; Diarrhea/microbiology ; Enterocytozoon/genetics/*isolation &amp; purification ; Fatty Acids, Unsaturated/*therapeutic use ; Feces/microbiology ; Female ; Humans ; Kidney Transplantation/*adverse effects ; Liver Transplantation/*adverse effects ; Microsporidiosis/*drug therapy/microbiology ; Sesquiterpenes/therapeutic use ; }, abstract = {We report the first successful use, to our knowledge, of fumagillin alone in a pediatric patient to cure intestinal microsporidiosis in a liver-kidney transplanted child. Detection of Enterocytozoon bieneusi in stool became negative from the first post-therapeutic control, while digestive symptoms disappeared in 4 days. During a 9-month follow-up, polymerase chain reaction and direct examinations remained negative for microsporidia in her feces. No major undesirable effects were noted during the anti-microsporidial therapy.}, }
@article {pmid24298714, year = {2013}, author = {Zanella Terrier, MC and Frossard, JL and Simonet, ML}, title = {[Recurrent Clostridium difficile infections: the importance of the intestinal microbiota].}, journal = {Revue medicale suisse}, volume = {9}, number = {402}, pages = {1898, 1900-4}, pmid = {24298714}, issn = {1660-9379}, mesh = {Anti-Bacterial Agents/adverse effects ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/epidemiology/etiology/*therapy ; Diarrhea/microbiology/*therapy ; Feces/microbiology ; Humans ; Intestines/*microbiology ; Recurrence ; }, abstract = {Clostridium difficile infections (CDI) represent 20-30% of diarrhea caused by antibiotics and relapse in more than 25% of cases after treatment with metronidazole or vancomycin. Given the high prevalence of CDI and the significant rate of recurrence despite successful initial treatment, CDI therapy represents a real challenge. A better understanding of the intestinal microbiota and its role in CDI opens the way to promising new therapeutic approaches, such as fecal transplantation. The studies published to date, although few, conclude a certain effectiveness of fecal transplantation in recurrent CDI. Further studies are needed to confirm its effectiveness, determine the long-term consequences as well as good administration practices.}, }
@article {pmid24296579, year = {2014}, author = {Khoruts, A}, title = {Faecal microbiota transplantation in 2013: developing human gut microbiota as a class of therapeutics.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {11}, number = {2}, pages = {79-80}, doi = {10.1038/nrgastro.2013.231}, pmid = {24296579}, issn = {1759-5053}, mesh = {Anti-Bacterial Agents/adverse effects/pharmacology ; Clostridium Infections/*therapy ; Feces/microbiology ; Gastrointestinal Tract/*microbiology ; Host-Pathogen Interactions/physiology ; Humans ; Microbiota/drug effects/*physiology ; Therapeutics/*trends ; Transplantation ; }, abstract = {Although the idea of faecal transplantation dates back many decades, only with advances in scientific technologies can we begin systematic development of this new class of therapeutics. The primary focus remains on treatment of Clostridium difficile infection—new applications are beginning to emerge, but a long journey remains ahead.}, }
@article {pmid24298178, year = {2013}, author = {Landy, J and Hart, A}, title = {The microbiome in inflammatory bowel disease and beyond.}, journal = {Clinical medicine (London, England)}, volume = {13 Suppl 6}, number = {}, pages = {s29-31}, doi = {10.7861/clinmedicine.13-6-s29}, pmid = {24298178}, issn = {1473-4893}, mesh = {Anti-Bacterial Agents ; Colitis, Ulcerative ; Crohn Disease ; Humans ; *Inflammatory Bowel Diseases/immunology ; *Microbiota ; Probiotics ; }, abstract = {The diverse and complex community of microorganisms that has co-evolved with the human gut is vital to intestinal functioning, and disturbances in the microbiota and its relationship with the host immune system have been linked to inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. This has suggested several treatment options, including antibiotics, probiotics and faecal transplantation. The human microbiome project has been established to enable comprehensive characterisation of the human microbiota and in the coming years, knowledge in this area is expected to continue to expand.}, }
@article {pmid24285002, year = {2014}, author = {Honda, H and Dubberke, ER}, title = {The changing epidemiology of Clostridium difficile infection.}, journal = {Current opinion in gastroenterology}, volume = {30}, number = {1}, pages = {54-62}, doi = {10.1097/MOG.0000000000000018}, pmid = {24285002}, issn = {1531-7056}, mesh = {Anti-Bacterial Agents/therapeutic use ; Enterocolitis, Pseudomembranous/diagnosis/drug therapy/*epidemiology ; Evidence-Based Medicine/methods ; Humans ; Incidence ; Risk Factors ; }, abstract = {PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is a growing concern and has a substantial impact on morbidity and mortality. Epidemiology of CDI has dramatically changed over the last decade. Diagnostic and treatment strategies are even more complicated given the wide variety of available diagnostic methods and the emergence of refractory or recurrent CDI. This review is intended to provide information on current CDI epidemiology and guidance for evidence-based diagnosis and management strategies.<br><br>RECENT FINDINGS: Various studies from the United States, Europe, and Canada revealed increased incidence of CDI since 2000. Although CDI has long been associated with healthcare settings, recent studies indicate it is more common in the community than previously recognized. For diagnostic strategies, newer testing methods, including nucleic acid amplification tests, have enhanced sensitivity compared with toxin testing, but at the expense of decreased specificity. New agents for treating CDI are being developed and higher quality data to support fecal microbiota transplantation for treating recurrent CDI are emerging.<br><br>SUMMARY: CDI epidemiology continues to evolve. Prompt recognition and an evidence-based treatment approach is the key to successfully manage CDI. Further, studies on diagnostic and therapeutic strategies are needed to further improve patient outcomes.}, }
@article {pmid24284963, year = {2014}, author = {Weingarden, AR and Chen, C and Bobr, A and Yao, D and Lu, Y and Nelson, VM and Sadowsky, MJ and Khoruts, A}, title = {Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {306}, number = {4}, pages = {G310-9}, pmid = {24284963}, issn = {1522-1547}, support = {UL1 TR000114/TR/NCATS NIH HHS/United States ; R21 AI-091907/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bile Acids and Salts/*metabolism ; Biological Therapy/*methods ; Clostridioides difficile/classification/genetics/isolation &amp; purification/*pathogenicity ; Enterocolitis, Pseudomembranous/diagnosis/metabolism/microbiology/*therapy ; Feces/*chemistry/*microbiology ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Intestines/*microbiology ; Male ; Metabolomics ; *Microbiota ; Middle Aged ; Prospective Studies ; Recurrence ; Ribotyping/methods ; Time Factors ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for refractory, recurrent Clostridium difficile infection (CDI), which develops following antibiotic treatments. Intestinal microbiota play a critical role in the metabolism of bile acids in the colon, which in turn have major effects on the lifecycle of C. difficile bacteria. We hypothesized that fecal bile acid composition is altered in patients with recurrent CDI and that FMT results in its normalization. General metabolomics and targeted bile acid analyses were performed on fecal extracts from patients with recurrent CDI treated with FMT and their donors. In addition, 16S rRNA gene sequencing was used to determine the bacterial composition of pre- and post-FMT fecal samples. Taxonomic bacterial composition of fecal samples from FMT recipients showed rapid change and became similar to the donor after the procedure. Pre-FMT fecal samples contained high concentrations of primary bile acids and bile salts, while secondary bile acids were nearly undetectable. In contrast, post-FMT fecal samples contained mostly secondary bile acids, as did non-CDI donor samples. Therefore, our analysis showed that FMT resulted in normalization of fecal bacterial community structure and metabolic composition. Importantly, metabolism of bile salts and primary bile acids to secondary bile acids is disrupted in patients with recurrent CDI, and FMT corrects this abnormality. Since individual bile salts and bile acids have pro-germinant and inhibitory activities, the changes suggest that correction of bile acid metabolism is likely a major mechanism by which FMT results in a cure and prevents recurrence of CDI.}, }
@article {pmid24282348, year = {2013}, author = {Nitzan, O and Elias, M and Chazan, B and Raz, R and Saliba, W}, title = {Clostridium difficile and inflammatory bowel disease: role in pathogenesis and implications in treatment.}, journal = {World journal of gastroenterology}, volume = {19}, number = {43}, pages = {7577-7585}, pmid = {24282348}, issn = {2219-2840}, mesh = {Anti-Bacterial Agents/therapeutic use ; Biological Therapy ; Clostridioides difficile/drug effects/isolation &amp; purification/*pathogenicity ; Disease Progression ; Enterocolitis, Pseudomembranous/epidemiology/immunology/*microbiology/therapy ; Feces/microbiology ; Humans ; Incidence ; Inflammatory Bowel Diseases/epidemiology/immunology/*microbiology/therapy ; Intestines/immunology/*microbiology ; Prevalence ; Risk Factors ; Treatment Outcome ; Virulence ; }, abstract = {Clostridium difficile (C. difficile) is the leading cause of antibiotic associated colitis and nosocomial diarrhea. Patients with inflammatory bowel disease (IBD) are at increased risk of developing C. difficile infection (CDI), have worse outcomes of CDI-including higher rates of colectomy and death, and experience higher rates of recurrence. However, it is still not clear whether C. difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment. The burden of CDI has increased dramatically over the past decade, with severe outbreaks described in many countries, which have been attributed to a new and more virulent strain. A parallel rise in the incidence of CDI has been noted in patients with IBD. IBD patients with CDI tend be younger, have less prior antibiotic exposure, and most cases of CDI in these patients represent outpatient acquired infections. The clinical presentation of CDI in these patients can be unique-including diversion colitis, enteritis and pouchitis, and typical findings on colonoscopy are often absent. Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation, and the prognostic implications of CDI in these patients, it is recommended to test all IBD patients hospitalized with a disease flare for C. difficile. Treatment includes general measures such as supportive care and infection control measures. Antibiotic therapy with either oral metronidazole, vancomycin, or the novel antibiotic-fidaxomicin, should be initiated as soon as possible. Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI. The aim of this paper is to review recent data on CDI in IBD: role in pathogenesis, diagnostic methods, optional treatments, and outcomes of these patients.}, }
@article {pmid24279951, year = {2013}, author = {van Nood, E and Keller, JJ and Kuijper, EJ and Speelman, P}, title = {[New treatment options for infections with Clostridium difficile].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {157}, number = {48}, pages = {A6580}, pmid = {24279951}, issn = {1876-8784}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile/drug effects/pathogenicity ; Clostridium Infections/drug therapy ; Enterocolitis, Pseudomembranous/*drug therapy ; Feces/microbiology ; Fidaxomicin ; Humans ; Netherlands ; Probiotics/*therapeutic use ; Recurrence ; Treatment Outcome ; }, abstract = {Currently available broad spectrum antibiotics are not sufficiently effective against recurrent Clostridium difficile infections (CDI). Donor faecal microbiota transplantation is a very effective treatment for second and recurrent infection but is time-consuming and requires careful screening of donors. The new narrow spectrum antibiotic fidaxomicin is a good alternative in a first CDI or a first recurrence, but treatment is expensive and there are no data on its effectiveness in a second or later recurrence. Fidaxomicin is less effective against infections caused by the Ribotype 027 strain, a virulent strain that is regularly encountered in the Netherlands. The effectiveness of various other promising narrow spectrum antibiotics is currently being investigated. Medications that support the gut flora or the immune system seem to offer new perspectives. Expectations for the currently available probiotic preparations and toxin binders are not high.}, }
@article {pmid24275671, year = {2014}, author = {Lo Vecchio, A and Cohen, MB}, title = {Fecal microbiota transplantation for Clostridium difficile infection: benefits and barriers.}, journal = {Current opinion in gastroenterology}, volume = {30}, number = {1}, pages = {47-53}, doi = {10.1097/MOG.0000000000000023}, pmid = {24275671}, issn = {1531-7056}, mesh = {Enterocolitis, Pseudomembranous/*therapy ; Evidence-Based Medicine/methods ; Feces/*microbiology ; Humans ; Intestines/microbiology ; *Microbiota ; Recurrence ; Tissue Transplantation/adverse effects/*methods ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: The incidence and severity of Clostridium difficile infection (CDI) have increased worldwide in the past two decades. A principal function of the gut microbiota is to protect the intestine against colonization by exogenous pathogens. Increasingly, the gut microbiota have been shown to influence susceptibility to other genetic and environmentally acquired conditions. Transplantation of healthy donor fecal material in patients with CDI may re-establish the normal composition of the gut microbiota and has been shown to be effective in recurrent CDI. We intend to review the most recent data on fecal microbiota transplantation (FMT) and critically discuss potential advantages and handicaps of this new therapeutic approach.<br><br>RECENT FINDINGS: Evidence from case series and only one randomized clinical trial suggests that FMT is able to restore the wide diversity of microflora, improve C. difficile-related symptoms and prevent CDI recurrence.<br><br>SUMMARY: FMT is a promising treatment option for serious and recurrent CDI, and current evidence (although weak) demonstrates consistent and excellent efficacy in clinical outcomes. However, many questions should be answered before it may be recommended as routine standard treatment. Mechanisms of action need to be better understood. Long-term follow-up studies are needed to determine long-lasting effects (including the association with autoimmune diseases).}, }
@article {pmid24275541, year = {2014}, author = {Koboziev, I and Reinoso Webb, C and Furr, KL and Grisham, MB}, title = {Role of the enteric microbiota in intestinal homeostasis and inflammation.}, journal = {Free radical biology &amp; medicine}, volume = {68}, number = {}, pages = {122-133}, pmid = {24275541}, issn = {1873-4596}, support = {R01 DK091269/DK/NIDDK NIH HHS/United States ; DK091269/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Gastrointestinal Tract/*microbiology/pathology ; Homeostasis ; Humans ; Inflammation/*microbiology/pathology ; Inflammatory Bowel Diseases ; Intestinal Mucosa/*microbiology/pathology ; *Microbiota ; }, abstract = {The mammalian intestine encounters many more microorganisms than any other tissue in the body thus making it the largest and most complex component of the immune system. Indeed, there are greater than 100 trillion (10(14)) microbes within the healthy human intestine, and the total number of genes derived from this diverse microbiome exceeds that of the entire human genome by at least 100-fold. Our coexistence with the gut microbiota represents a dynamic and mutually beneficial relationship that is thought to be a major determinant of health and disease. Because of the potential for intestinal microorganisms to induce local and/or systemic inflammation, the intestinal immune system has developed a number of immune mechanisms to protect the host from pathogenic infections while limiting the inflammatory tissue injury that accompanies these immune responses. Failure to properly regulate intestinal mucosal immunity is thought to be responsible for the inflammatory tissue injury observed in the inflammatory bowel diseases (IBD; Crohn disease, ulcerative colitis). An accumulating body of experimental and clinical evidence strongly suggests that IBD results from a dysregulated immune response to components of the normal gut flora in genetically susceptible individuals. The objective of this review is to present our current understanding of the role that enteric microbiota play in intestinal homeostasis and pathogenesis of chronic intestinal inflammation.}, }
@article {pmid24265942, year = {2013}, author = {Heimesaat, MM and Kupz, A and Fischer, A and Nies, DH and Grass, G and Göbel, UB and Bereswill, S}, title = {Colonization resistance against genetically modified Escherichia coli K12 (W3110) strains is abrogated following broad-spectrum antibiotic treatment and acute ileitis.}, journal = {European journal of microbiology &amp; immunology}, volume = {3}, number = {3}, pages = {222-228}, pmid = {24265942}, issn = {2062-509X}, abstract = {Escherichia coli K12 (EcK12) is commonly used for gene technology purposes and regarded as a security strain due to its inability to adhere to epithelial cells. The conventional intestinal microbiota composition is critical for physiological colonization resistance against most bacterial species including pathogens. We were therefore interested whether intestinal colonization by a genetically modified EcK12 (W3110) strain carrying a chloramphenicol resistance cassette was facilitated following broad-spectrum antibiotic treatment eradicating the intestinal microbiota or induction of small intestinal inflammation accompanied by distinct microbiota shifts. Whereas conventional C57BL/6 and BALB/c mice had virtually expelled the EcK12 (W3110) strain within the first 3 days upon peroral infection, EcK12 (W3110) could establish within the small and large intestines of gnotobiotic mice generated by quintuple antibiotic treatment. Gnotobiotic mice perorally infected with EcK12 (W3110) plus fecal transplant from conventional donors harbored lower intestinal EcK12 (W3110) loads compared to animals challenged with EcK12 (W3110) alone. Furthermore, EcK12 (W3110) infection of conventional mice after but not before induction of ileitis resulted in stable colonization of ileum and colon by EcK12 (W3110). Taken together, broad-spectrum antibiotic treatment and intestinal inflammation compromise colonization resistance and thus facilitate colonization of the intestinal tract with genetically modified EcK12 security strains.}, }
@article {pmid24265916, year = {2013}, author = {Heimesaat, MM and Plickert, R and Fischer, A and Göbel, UB and Bereswill, S}, title = {Can microbiota transplantation abrogate murine colonization resistance against Campylobacter jejuni?.}, journal = {European journal of microbiology &amp; immunology}, volume = {3}, number = {1}, pages = {36-43}, pmid = {24265916}, issn = {2062-509X}, abstract = {Enterocolitis caused by Campylobacter jejuni represents an important socioeconomic burden worldwide. The host-specific intestinal microbiota is essential for maintaining colonization resistance (CR) against C. jejuni in conventional mice. Notably, CR is abrogated by shifts of the intestinal microbiota towards overgrowth with commensal E. coli during acute ileitis. Thus, we investigated whether oral transplantation (TX) of ileal microbiota derived from C. jejuni susceptible mice with acute ileitis overcomes CR of healthy conventional animals. Four days following ileitis microbiota TX or ileitis induction and right before C. jejuni infection, mice displayed comparable loads of main intestinal bacterial groups as shown by culture. Eight days following ileitis induction, but not ileal microbiota TX, however, C. jejuni could readily colonize the gastrointestinal tract of conventional mice and also translocate to extra-intestinal tissue sites such as mesenteric lymph nodes, spleen, liver, and blood within 4 days following oral infection. Of note, C. jejuni did not further deteriorate histopathology following ileitis induction. Lack of C. jejuni colonization in TX mice was accompanied by a decrease of commensal E. coli loads in the feces 4 days following C. jejuni infection. In summary, oral ileal microbiota TX from susceptible donors is not sufficient to abrogate murine CR against C. jejuni.}, }
@article {pmid24258390, year = {2014}, author = {Chandra, A and Kumar, A and Noushif, M and Gupta, V and Kumar, V and Srivastav, PK and Malhotra, HS and Kumar, M and Ghoshal, UC}, title = {Neurovascular antropylorus perineal transposition using inferior rectal nerve anastomosis for total anorectal reconstruction: preliminary report in humans.}, journal = {Techniques in coloproctology}, volume = {18}, number = {6}, pages = {535-542}, pmid = {24258390}, issn = {1128-045X}, mesh = {Adolescent ; Adult ; Anal Canal/physiopathology/*surgery ; Anastomosis, Surgical ; Colostomy ; Electromyography ; Endoscopy, Gastrointestinal ; Fecal Incontinence/etiology/physiopathology/*surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Manometry ; Middle Aged ; Perineum/*innervation/*surgery ; Pylorus/blood supply/innervation/*transplantation ; Plastic Surgery Procedures/*methods ; Rectum/*innervation ; Treatment Outcome ; }, abstract = {BACKGROUND: Technical feasibility of inferior rectal nerve anastomosis to the anterior vagus branch of the perineally transposed antropyloric valve for total anorectal reconstruction has been previously demonstrated in cadavers. To the best of our knowledge, the present study is the first report of using this procedure in humans.<br><br>METHODS: Eight patients [mean age 35.5&#xa0;years (range 15-55&#xa0;years); (male/female&#xa0;=&#xa0;7:1)] underwent the procedure. The antropyloric valve with its anterior vagus branch was mobilized based on the left gastroepiploic arterial pedicle. The antral end was anastomosed to the distal colon. The anterior vagus nerve was anastomosed by epineural technique to the inferior rectal nerve in the perineum. A diverting proximal colostomy was maintained for 6&#xa0;months. Anatomical integrity of the graft (on magnetic resonance imaging scans), its arterial pedicle (on computed tomography angiogram) and neural continuity (on ultrasound and pyloric electromyography) were assessed. Functional assessment was performed using barium retention studies, endoscopy, manometry and fecal incontinence scores.<br><br>RESULTS: Tension-free end-to-end anastomosis of the anterior vagus nerve to the right (n&#xa0;=&#xa0;7) and left (n&#xa0;=&#xa0;1) inferior rectal nerve was achieved. An intact left gastroepiploic pedicle, a healthy graft and neural continuity were visualized on perineal ultrasound. Electromyographic activity was noticed on neural stimulation. Endoscopy and barium studies showed voluntary antral contraction and contrast retention, respectively, in all patients. The mean resting and squeeze pressures were 26.25&#xa0;mmHg (range 16-62&#xa0;mmHg) and 50.25&#xa0;mmHg (range 16-113&#xa0;mmHg), respectively. St. Mark's incontinence scores varied between 7 and 12. There were no major surgical complications.<br><br>CONCLUSIONS: Pudendal (inferior rectal) innervation of the perineally transposed antropylorus in total anorectal reconstruction is feasible and may improve outcomes in selected patients with end-stage fecal incontinence.}, }
@article {pmid24257037, year = {2014}, author = {Borody, TJ and Brandt, LJ and Paramsothy, S}, title = {Therapeutic faecal microbiota transplantation: current status and future developments.}, journal = {Current opinion in gastroenterology}, volume = {30}, number = {1}, pages = {97-105}, pmid = {24257037}, issn = {1531-7056}, mesh = {Autoimmune Diseases/therapy ; Enterocolitis, Pseudomembranous/therapy ; Feces/*microbiology ; Humans ; Inflammatory Bowel Diseases/therapy ; Intestinal Diseases/*therapy ; Intestines/microbiology ; Irritable Bowel Syndrome/therapy ; *Microbiota ; Recurrence ; Tissue Transplantation/methods/*trends ; }, abstract = {PURPOSE OF REVIEW: Faecal microbiota transplantation (FMT) has undergone dramatic progression over the past year and continues to evolve as knowledge of the gastrointestinal microbiota (GiMb) develops. This review summarizes therapeutic advances in FMT, latest FMT therapies and presents the potential of FMT therapeutics in other gastrointestinal and extra-intestinal conditions.<br><br>RECENT FINDINGS: The GiMb is now known to have a central role in the pathogenesis of many diseases. The success of FMT in curing Clostridium difficile infection (CDI) is well established and preliminary findings in other gastrointestinal conditions are promising. Published data from over 500 CDI cases suggest that FMT is generally well tolerated with minimal side effects. The commercial potential of FMT is being explored with several products under development, including frozen GiMb extract, which has been shown highly effective in treating relapsing CDI. Such products will likely become more available in coming years and revolutionize the availability and method of delivery of GiMb.<br><br>SUMMARY: Recent literature unequivocally supports the use of FMT in treating relapsing CDI. Trials are underway to determine the therapeutic potential of FMT in other conditions, particularly inflammatory bowel disease. Therapeutic FMT is a dynamic field with new and emerging indications along with ongoing developments in optimal mode of administration.}, }
@article {pmid24246975, year = {2013}, author = {Mondot, S and de Wouters, T and Doré, J and Lepage, P}, title = {The human gut microbiome and its dysfunctions.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {31}, number = {3-4}, pages = {278-285}, doi = {10.1159/000354678}, pmid = {24246975}, issn = {1421-9875}, mesh = {Biodiversity ; Gastrointestinal Tract/*microbiology/*pathology ; Humans ; Microbiota/*physiology ; Obesity/microbiology/pathology ; }, abstract = {The human gastrointestinal tract hosts more than 100 trillion bacteria and archaea, which together make up the gut microbiota. The amount of bacteria in the human gut outnumbers human cells by a factor of 10, but some finely tuned mechanisms allow these microorganisms to colonize and survive within the host in a mutual relationship. The human gut microbiota co-evolved with humans to achieve a symbiotic relationship leading to physiological homeostasis. The microbiota provides crucial functions that human cannot exert themselves while the human host provides a nutrient-rich environment. Chaotic in the early stages of life, the assembly of the human gut microbiota remains globally stable over time in healthy conditions and absence of perturbation. Following perturbation, such as antibiotic treatment, bacteria will recolonize the niches with a composition and diversity similar to the basal level since the ecosystem is highly resilient. Yet, recurrent perturbations lead to a decrease in resilience capacity of the gut microbiome. Shifts in the bacterial composition and diversity of the human gut microbiota have been associated with intestinal dysfunctions such as inflammatory bowel disease and obesity. More than specific bacteria, a general destructuration of the ecosystem seems to be involved in these pathologies. Application of metagenomics to this environment may help in deciphering key functions and correlation networks specifically involved in health maintenance. In term, fecal transplant and synthetic microbiome transplant might be promising therapies for dysbiosis-associated diseases.}, }
@article {pmid24244876, year = {2013}, author = {Kellermayer, R}, title = {Prospects and challenges for intestinal microbiome therapy in pediatric gastrointestinal disorders.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {4}, number = {4}, pages = {91-93}, pmid = {24244876}, issn = {2150-5330}, abstract = {Fecal microbiome (microbiota) transplantation is an emerging treatment not only for refractory/recurrent Clostridium difficile infections and chronic gastrointestinal diseases, but also for metabolic syndrome, and even possibly for neurological disorders. This non-conventional therapy has been perhaps more appropriately designated as fecal bacteriotherapy (FB) as well. The employment of FB is spreading into pediatric gastroenterology. This focused review highlights the pediatric applications of FB and discusses hypotheses for its mechanism of action. We propose that intestinal microbiome therapy may be a more appropriate term for FB, which integrates its potential future applications.}, }
@article {pmid24241245, year = {2014}, author = {van Nood, E and Speelman, P and Nieuwdorp, M and Keller, J}, title = {Fecal microbiota transplantation: facts and controversies.}, journal = {Current opinion in gastroenterology}, volume = {30}, number = {1}, pages = {34-39}, doi = {10.1097/MOG.0000000000000024}, pmid = {24241245}, issn = {1531-7056}, mesh = {Clinical Protocols ; Donor Selection/methods ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Inflammatory Bowel Diseases/therapy ; Intestines/microbiology ; Metabolic Syndrome/therapy ; *Microbiota ; Recurrence ; Tissue Transplantation/adverse effects/*methods ; }, abstract = {PURPOSE OF REVIEW: To review the current evidence on fecal microbiota transplantations (FMTs) for recurrent Clostridium difficile infections (CDIs), metabolic syndrome and inflammatory bowel disease.<br><br>RECENT FINDINGS: Recently, a randomized trial confirmed the efficacy of this treatment strategy in patients with recurrent CDI. For other disorders, evidence is still limited. To date, studies have been performed to try and influence the course of metabolic syndrome and inflammatory bowel disease.<br><br>SUMMARY: There is increasing interest in the role of altered microbiota in the development of a myriad of diseases. Together with new insights comes an interest in influencing this altered microbiota as a potential target for therapy. FMTs are effective against recurrent CDI, a disorder caused by disruption of the normal microbiota. Restoration of intestinal flora and thereby restoration of colonization resistance is thought to be the mechanism responsible for cure. With the developments in FMT and the extension of this treatment modality to both intestinal and extra-intestinal diseases, a new field of targeted therapy awaits. The ultimate goal is the development of powerful probiotic regimens that can replace FMT. Currently, FMT should only be given in a strict experimental setting for other conditions than CDI.}, }
@article {pmid24239403, year = {2014}, author = {Gordon, H and Harbord, M}, title = {A patient with severe Crohn's colitis responds to Faecal Microbiota Transplantation.}, journal = {Journal of Crohn's &amp; colitis}, volume = {8}, number = {3}, pages = {256-257}, doi = {10.1016/j.crohns.2013.10.007}, pmid = {24239403}, issn = {1876-4479}, mesh = {Adult ; Biological Therapy/*methods ; Crohn Disease/*therapy ; Feces/*microbiology ; Humans ; Male ; *Microbiota ; }, }
@article {pmid24222969, year = {2013}, author = {Zhang, FM and Wang, HG and Wang, M and Cui, BT and Fan, ZN and Ji, GZ}, title = {Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {19}, number = {41}, pages = {7213-7216}, pmid = {24222969}, issn = {2219-2840}, mesh = {Adult ; Biological Therapy/*methods ; Clinical Trials as Topic ; Colon/*microbiology ; Crohn Disease/complications/diagnosis/microbiology/*therapy ; Endoscopy, Gastrointestinal ; Feces/*microbiology ; Humans ; Intestinal Fistula/diagnosis/etiology/microbiology/*therapy ; Male ; Pilot Projects ; Remission Induction ; Severity of Illness Index ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {The concept of fecal microbiota transplantation (FMT) has been used in traditional Chinese medicine at least since the 4(th) century. Evidence from recent human studies strongly supports the link between intestinal bacteria and inflammatory bowel disease. We proposed that standardized FMT might be a promising rescue therapy for refractory inflammatory bowel disease. However, there were no reports of FMT used in patients with severe Crohn's disease (CD). Here, we report the successful treatment of standardized FMT as a rescue therapy for a case of refractory CD complicated with fistula, residual Barium sulfate and formation of intraperitoneal large inflammatory mass. As far as we know, this is the first case of severe CD treated using FMT through mid-gut.}, }
@article {pmid24187630, year = {2013}, author = {Shapira, I and Sultan, K and Lee, A and Taioli, E}, title = {Evolving concepts: how diet and the intestinal microbiome act as modulators of breast malignancy.}, journal = {ISRN oncology}, volume = {2013}, number = {}, pages = {693920}, pmid = {24187630}, issn = {2090-5661}, support = {U10 CA035279/CA/NCI NIH HHS/United States ; }, abstract = {The intestinal microbiome plays an important role in human physiology. Next-generation sequencing technologies, knockout and gnotobiotic mouse models, fecal transplant data and epidemiologic studies have accelerated our understanding of microbiome abnormalities seen in immune diseases and malignancies. Dysbiosis is the disturbed microbiome ecology secondary to external pressures such as host diseases, medications, diet and genetic conditions often leading to abnormalities of the host immune system. Specifically dysbiosis has been shown to lower circulating lymphocytes, and increase neutrophil to lymphocyte ratio, a finding which has been associated with a decreased survival in women with breast cancers. Dysbiosis also plays a role in the recycling of estrogens via the entero-hepatic circulation, increasing estrogenic potency in the host, which is another leading cause of breast malignancy. Non-modifiable factors such as age and genetic mutations disrupt the microbiome, but modifiable factors such as diet may also lead to profound disruptions as well. A better understanding of dietary factors and how they disrupt the microbiome may lead to beneficial nutritional interventions for breast cancer patients.}, }
@article {pmid24184170, year = {2014}, author = {Quera, R and Espinoza, R and Estay, C and Rivera, D}, title = {Bacteremia as an adverse event of fecal microbiota transplantation in a patient with Crohn's disease and recurrent Clostridium difficile infection.}, journal = {Journal of Crohn's &amp; colitis}, volume = {8}, number = {3}, pages = {252-253}, doi = {10.1016/j.crohns.2013.10.002}, pmid = {24184170}, issn = {1876-4479}, mesh = {Bacteremia/*microbiology ; Biological Therapy/*methods ; Clostridioides difficile ; Clostridium Infections/complications/*therapy ; Crohn Disease/complications/*microbiology ; Feces/*microbiology ; Humans ; Male ; Microbiota ; Middle Aged ; Recurrence ; }, }
@article {pmid24176407, year = {2013}, author = {Boissier, R and Karsenty, G}, title = {[Prognosis of neurological bladders].}, journal = {Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie}, volume = {23}, number = {14}, pages = {1181-1185}, doi = {10.1016/j.purol.2013.09.023}, pmid = {24176407}, issn = {1166-7087}, mesh = {Humans ; Kidney/diagnostic imaging/physiology ; Paralysis/physiopathology ; Patient Care Team ; Prognosis ; Quality of Life ; Radiography ; Ultrasonography ; Urinary Bladder, Neurogenic/*physiopathology/therapy ; Urination/physiology ; Urination Disorders/physiopathology/therapy ; Urodynamics/physiology ; }, abstract = {Numerous neurological diseases may hurt the neurological command of the miction and thus provoke the dysfunctions of the bladder and/or the urinary sphincter. These dysfunctions leads to annoying symptoms (incontinence, retention or both) but can also cause grave complications (renal infections, calculations, renal insufficiency, tumor of bladder). The forecast of the neurological bladders consists to prevent the urinary complications and to improve the comfort/quality of life. The initial care must be early and multidisciplinary. The objective of a low-pressure bladder emptied regularly without permanent drainage is common to all the situations. The objective of a dry and autonomous patient for the elimination of the urine is the main goal for the optimization of the quality of life. The restoration of a sexuality, a fertility, a control of the continence and the faecal exemption are also important parameters to improve of the quality of life.}, }
@article {pmid24165451, year = {2013}, author = {Jacobs, SA and Lane, FL and Pham, QA and Nistor, G and Robles, R and Chua, C and Boubion, B and Osann, K and Keirstead, H}, title = {Safety assessment of myogenic stem cell transplantation and resulting tumor formation.}, journal = {Female pelvic medicine &amp; reconstructive surgery}, volume = {19}, number = {6}, pages = {362-368}, doi = {10.1097/SPV.0000000000000035}, pmid = {24165451}, issn = {2151-8378}, mesh = {Anal Canal/pathology ; Animals ; Anus Neoplasms/epidemiology ; Cell Movement ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Fecal Incontinence/*surgery ; Female ; Humans ; Prospective Studies ; Rats ; Rats, Sprague-Dawley ; *Stem Cell Transplantation/adverse effects ; }, abstract = {OBJECTIVES: To assess for stem cell migration to liver and lung after transplantation in injured rat anal sphincters. To evaluate histological findings of unanticipated ectopic foci of growth.<br><br>METHODS: This is a prospective study involving 33 female virginal Sprague-Dawley rats. Anal sphincters were transected and repaired under sterile technique. Animals received injections of 5.0 &#xd7; 10 myogenic stem cells (24 rats) or sham control (9 rats) and were killed on day 30. Liver and lung samples were obtained. Upon encountering abnormal foci of growth, further staining protocols were employed. Enzyme-linked immunosorbent assay studies evaluated stem cell media for in vitro growth factor secretion.<br><br>RESULTS: No evidence of cell migration to liver or lung was found at the time of euthanasia in any study animal. Ectopic foci of growth were noted in 2 transplant rats. Further histological evaluations of these growths were consistent with benign tumors: no nuclear abnormalities and no evidence of proliferation at day 30. Enzyme-linked immunosorbent assay studies demonstrated positive secretion of vascular endothelial growth factor and insulin growth factor into the media of cultured rat myogenic stem cells.<br><br>CONCLUSIONS: Whereas distant migration was not encountered in the liver or lung, 2 transplanted rats developed abnormal foci of growth, that is, tumors, from the external anal sphincter-raising further safety questions. Additional evaluation of these foci seemed benign. Possible explanations include cell trapping, stem cell overgrowth, and/or paracrine factors. The lack of cell migration supports that future investigation of safety parameters could focus locally.}, }
@article {pmid24165333, year = {2013}, author = {Mughal, M and Baker, RJ and Muneer, A and Mosahebi, A}, title = {Reconstruction of perineal defects.}, journal = {Annals of the Royal College of Surgeons of England}, volume = {95}, number = {8}, pages = {539-544}, pmid = {24165333}, issn = {1478-7083}, mesh = {Autografts ; Humans ; Negative-Pressure Wound Therapy/methods ; Perineum/*surgery ; Rectus Abdominis/transplantation ; *Surgical Flaps ; Wound Healing/physiology ; }, abstract = {INTRODUCTION: Perineal defects are commonly encountered in an oncological setting although they may also present as a result of trauma and infection (eg following Fournier's gangrene). Reconstruction of these poses functional as well as aesthetic challenges. Skin coverage and tissue volume may both be required in addition to anogenital preservation or reconstruction. General prerequisites of an adequate reconstruction of perineal defects include provision of skin cover, well vascularised tissue to fill the dead space (reducing fluid collection and infection), vulvovaginal reconstruction and no faecal or urinary contamination.<br><br>METHODS: A literature search was performed using PubMed and MEDLINE &#xae; . The search terms included 'perineal defects', 'perineal reconstruction', 'perforator flaps for perineum', 'vulval flaps', 'secondary healing of wound' and 'vacuum assisted closure'. Backward chaining of reference lists from retrieved papers was also used to expand the search.<br><br>FINDINGS: Modern developments have led to an increased expectation in improved quality of life as the main goal of reconstruction, therefore necessitating surgery with less morbidity and early return to normal activity. Progress in microsurgical procedures has been the main recent advance in perineal reconstruction and, in future, refinements in perforator flap design and tissue engineering techniques will lead to even better reconstructions.}, }
@article {pmid24152015, year = {2014}, author = {Simojoki, ST and Kirjavainen, V and Rahiala, J and Kanerva, J}, title = {Surveillance cultures in pediatric allogeneic hematopoietic stem cell transplantation.}, journal = {Pediatric transplantation}, volume = {18}, number = {1}, pages = {87-93}, doi = {10.1111/petr.12177}, pmid = {24152015}, issn = {1399-3046}, mesh = {Adolescent ; Anemia, Aplastic/complications/therapy ; Anti-Infective Agents/therapeutic use ; Bacteria/isolation &amp; purification ; Bacterial Infections/*diagnosis/drug therapy ; Child ; Child, Preschool ; Feces/*microbiology ; Female ; Fungi/isolation &amp; purification ; Hematologic Neoplasms/complications/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Male ; Mycoses/*diagnosis/drug therapy ; Predictive Value of Tests ; Retrospective Studies ; Transplantation Conditioning ; Transplantation, Homologous ; }, abstract = {The value of surveillance cultures in predicting systemic infections and in guiding antimicrobial treatment is controversial. We investigated 57 pediatric allo-SCTs between 2007 and 2009. ALL (34), AML (5), and severe aplastic anemia (4) were the largest patient groups. Conditioning was TBI-based in 87% and 54% developed GVHD (21% grade III-IV). Of the 2594 weekly colonization samples, 24% were positive (fecal bacteria 86%, fecal fungi 16%, Clostridium difficile 16%; throat bacteria 17% and throat fungi 4%). Enterobacteria and enterococci were the most common fecal findings, staphylococci and streptococci in the throat. Of the bacterial stool samples pretransplant, 74% (mostly enterococci) were resistant to our first-line antibiotics (ceftazidime and cloxacillin). Candida species accounted for the majority of the fungal findings: 62% of the fecal and 78% in the throat. A total of 170 clinical infection episodes were recorded, and in 12 of these, the bacterial blood culture was positive. In 4/12 cases, the pathogen was detected in surveillance culture previously, leading to sensitivity and specificity of 33.3 and 47.4%, respectively. Positive predictive value of bacterial surveillance cultures was 0.9%. The antimicrobial treatment was changed in only five cases based on the surveillance culture results. Weekly surveillance cultures seldom provided clinical benefit and were not cost-effective.}, }
@article {pmid24148361, year = {2014}, author = {Hecht, GA and Blaser, MJ and Gordon, J and Kaplan, LM and Knight, R and Laine, L and Peek, R and Sanders, ME and Sartor, B and Wu, GD and Yang, VW}, title = {What is the value of a food and drug administration investigational new drug application for fecal microbiota transplantation to treat Clostridium difficile Infection?.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {12}, number = {2}, pages = {289-291}, doi = {10.1016/j.cgh.2013.10.009}, pmid = {24148361}, issn = {1542-7714}, mesh = {Biological Therapy/*methods ; Feces/*microbiology ; Humans ; *Investigational New Drug Application ; *Microbiota ; }, }
@article {pmid24143883, year = {2015}, author = {Bisson, A and Fréret, M and Drouot, L and Jean, L and Le Corre, S and Gourcerol, G and Doucet, C and Michot, F and Boyer, O and Lamacz, M}, title = {Restoration of anal sphincter function after myoblast cell therapy in incontinent rats.}, journal = {Cell transplantation}, volume = {24}, number = {2}, pages = {277-286}, doi = {10.3727/096368913X674053}, pmid = {24143883}, issn = {1555-3892}, mesh = {Anal Canal/pathology/*physiology ; Animals ; Cell- and Tissue-Based Therapy ; Cells, Cultured ; Disease Models, Animal ; Electric Stimulation ; Fecal Incontinence/pathology/*therapy ; Female ; Humans ; Muscle Contraction ; Myoblasts/cytology/*transplantation ; Rats ; Recovery of Function ; }, abstract = {Fecal incontinence (FI) remains a socially isolating condition with profound impact on quality of life for which autologous myoblast cell therapy represents an attractive treatment option. We developed an animal model of FI and investigated the possibility of improving sphincter function by intrasphincteric injection of syngeneic myoblasts. Several types of anal cryoinjuries were evaluated on anesthetized Fischer rats receiving analgesics. The minimal lesion yielding sustainable anal sphincter deficiency was a 90° cryoinjury of the sphincter, repeated after a 24-h interval. Anal sphincter pressure was evaluated longitudinally by anorectal manometry under local electrostimulation. Myoblasts were prepared using a protocol mimicking a clinical-grade process and further transduced with a GFP-encoding lentiviral vector before intrasphincteric injection. Experimental groups were uninjured controls, cryoinjured + PBS, and cryoinjured + myoblasts (different doses or injection site). Myoblast injection was well tolerated. Transferred myoblasts expressing GFP integrated into the sphincter and differentiated in situ into dystrophin-positive mature myofibers. Posttreatment sphincter pressures increased over time. At day 60, pressures in the treated group were significantly higher than those of PBS-injected controls and not significantly different from those of normal rats. Longitudinal follow-up showed stability of the therapeutic effect on sphincter function over a period of 6 months. Intrasphincteric myoblast injections at the lesion borders were equally as effective as intralesion administration, but an injection opposite to the lesion was not. These results provide proof of principle for myoblast cell therapy to treat FI in a rat model. This strategy is currently being evaluated in humans in a randomized double-blind placebo-controlled clinical trial.}, }
@article {pmid24136155, year = {2014}, author = {Contin, P and Kulu, Y and Bruckner, T and Sturm, M and Welsch, T and Müller-Stich, BP and Huber, J and Büchler, MW and Ulrich, A}, title = {Comparative analysis of late functional outcome following preoperative radiation therapy or chemoradiotherapy and surgery or surgery alone in rectal cancer.}, journal = {International journal of colorectal disease}, volume = {29}, number = {2}, pages = {165-175}, pmid = {24136155}, issn = {1432-1262}, mesh = {Aged ; *Chemoradiotherapy/adverse effects ; Fecal Incontinence/etiology/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Neoadjuvant Therapy/adverse effects ; Postoperative Care ; *Preoperative Care ; Rectal Neoplasms/*physiopathology/radiotherapy/surgery/*therapy ; Sexual Behavior ; Treatment Outcome ; }, abstract = {PURPOSE: This study evaluates the anorectal and genitourinary function of patients treated by preoperative short-term radiotherapy (RT) or chemoradiotherapy (CRT) followed by surgery and surgery alone for rectal cancer.<br><br>METHODS: For this study, a total of 613 patients, who were identified from a prospective rectal cancer database, underwent anterior resection of the rectum between October 2001 and December 2007. Standardized questionnaires were used to determine fecal incontinence, urinary, and sexual function. Relevant clinical variables were evaluated using univariate and multivariate analyses. Independent predictors of functional outcome were identified by a binary logistic regression analysis.<br><br>RESULTS: The data of 263 (43&#xa0;%) patients were available for analysis. On multivariate analysis, neoadjuvant RT (P&#x2009;<&#x2009;0.01) and low anterior resection (LAR) (P&#x2009;=&#x2009;0.049) were associated with fecal incontinence. In univariate analysis, fecal incontinence was linked to preoperative neoadjuvant treatment (RT and/or CRT vs. LAR) (P&#x2009;<&#x2009;0.01). The hazard ratio for developing fecal incontinence was 3.3 (1.6-6.8) for patients who received RT. One hundred twenty-five patients (51.2&#xa0;%) experienced urinary incontinence following surgery, the majority of whom were female (P&#x2009;<&#x2009;0.01). On univariate analysis, male sexual function was associated with age (P&#x2009;<&#x2009;0.01), ASA class (P&#x2009;=&#x2009;0.01) and LAR (P&#x2009;=&#x2009;0.01).<br><br>CONCLUSION: Multimodal therapy of low rectal cancer increases the incidence of fecal incontinence and negatively affects sexual function. The potential benefits of RT or CRT need to be balanced against the risk of increased bowel dysfunction when determining the appropriate treatment for individual patients with rectal cancer.}, }
@article {pmid24134195, year = {2013}, author = {Quigley, EM and Monsour, HP}, title = {The gut microbiota and the liver: implications for clinical practice.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {7}, number = {8}, pages = {723-732}, doi = {10.1586/17474124.2013.848167}, pmid = {24134195}, issn = {1747-4132}, mesh = {Anti-Bacterial Agents/therapeutic use ; Biological Therapy ; Feces/microbiology ; Hepatic Encephalopathy/microbiology ; Host-Pathogen Interactions ; Humans ; Intestines/drug effects/*microbiology ; Liver/drug effects/*microbiology ; Liver Diseases/diagnosis/*microbiology/therapy ; *Microbiota ; Peritonitis/microbiology ; Probiotics/therapeutic use ; Risk Factors ; Treatment Outcome ; }, abstract = {While a central role for the microbiota in the precipitation of infectious and non-infectious complications of liver disease has been long established, evidence for a more fundamental role in the etiology of several liver diseases continues to accumulate. However, though progress is rapidly occurring in this area, the definitive delineation of the precise relevance of changes in the microbiota to various forms and stages of liver disease is still far from complete. While high quality clinical evidence supports the use of antibiotic therapy, in the management of hepatic encephalopathy, spontaneous bacterial peritonitis and other infectious complications, how these interventions impact on the microbiota and microbiota-host interactions has not been clearly defined. Although probiotics and even, perhaps, fecal transplantation hold promise in the management of liver disease, and the potential impact of probiotics is supported by a considerable amount of laboratory data, high-quality clinical evidence is scanty.}, }
@article {pmid24133730, year = {2013}, author = {}, title = {Fecal microbiota transplantation for treatment of recurrent C. difficile infection.}, journal = {Clinical privilege white paper}, volume = {}, number = {246}, pages = {1-15}, pmid = {24133730}, mesh = {Biological Therapy/methods/*standards ; *Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Colon/*microbiology ; Credentialing/*standards ; Education, Medical, Graduate/*standards ; Feces/*microbiology ; Gastroenterology/*education/standards ; Humans ; Infectious Disease Medicine/*education/standards ; Intestines/*microbiology ; Joint Commission on Accreditation of Healthcare Organizations ; Medical Staff Privileges ; *Metagenome ; Microbiological Techniques/*standards ; Recurrence ; United States ; }, }
@article {pmid24132675, year = {2014}, author = {Weis, S and John, E and Lippmann, N and Mössner, J and Lübbert, C}, title = {[Clostridium difficile infection (CDI) in the course of time - an issue only for the internist?].}, journal = {Zentralblatt fur Chirurgie}, volume = {139}, number = {4}, pages = {460-468}, doi = {10.1055/s-0032-1328623}, pmid = {24132675}, issn = {1438-9592}, mesh = {Aminoglycosides/therapeutic use ; *Clostridioides difficile ; Colectomy ; Colostomy ; Cross-Sectional Studies ; Drug Resistance, Multiple, Bacterial ; Enterocolitis, Pseudomembranous/*epidemiology/*therapy ; Feces/microbiology ; Fidaxomicin ; Germany ; Humans ; Incidence ; Metronidazole/therapeutic use ; Recurrence ; Transplantation ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Toxigenic strains of Clostridium (C.) difficile are the most prevalent pathogens of antibiotic associated intestinal disease and nosocomial diarrhoea. During the last 10 years, incidences of C. difficile infection (CDI) have increased worldwide.<br><br>MATERIALS AND METHODS: With clinical and microbiological original data for 2002-2012 from the University Hospitals Leipzig and Halle (Saale), Germany, the authors illustrate the current situation regarding CDI in the states of Saxony and Saxony-Anhalt and exemplify the latest developments in terms of incidence, prevalence of resistance, diagnosis and treatment strategies regarding CDI with an emphasis on surgical options.<br><br>RESULTS: Following the general trend, at the University Hospitals of Leipzig and Halle (Saale) there was also an increase in incidence of CDI, especially of severe clinical courses. In primary and secondary care facilities, prevention of CDI is based on hygiene management and restricted usage of antibiotics, preferably as "Antibiotic Stewardship" programmes. In 2012, the new macrocyclic antibiotic Fidaxomicin was approved in the European Union for the treatment of CDI. The therapeutic armamentarium, previously based on metronidazole or vancomycin, has now been enriched by a substance that presumably will reduce the rate of recurrence of CDI. Moreover, early data from case series and controlled trials suggest that the re-establishment of eubiosis in the colon of patients with recurrent CDI by stool transplantation from healthy donors is an alternative to antibiotics. Standard surgical intervention for refractory CDI is subtotal colectomy with terminal ileostomy. In patients with adequate life expectancy and without organ dysfunction, a colon-saving surgical technique should be considered.<br><br>CONCLUSION: Taking antibiotics for most remains the main risk factor for suffering from symptomatic CDI. With the introduction of Fidaxomicin there is hope for an improvement in the conservative treatment of CDI. Stool transplants from healthy donors are now considered to be better than giving antibiotics for severe CDI, but this treatment has not found broad acceptance yet. In cases with a lack of early treatment success, the surgeon must be consulted. Here, the evidence for preferably colon-saving surgical procedures is so far unfortunately low.}, }
@article {pmid24132529, year = {2014}, author = {Patel, LN and Schairer, J and Shen, B}, title = {Fecal transplantation therapy for Clostridium difficile-associated pouchitis.}, journal = {International journal of colorectal disease}, volume = {29}, number = {2}, pages = {263-264}, pmid = {24132529}, issn = {1432-1262}, mesh = {Adult ; Aminoglycosides/pharmacology/therapeutic use ; Child ; Clostridioides difficile/*physiology ; Enterocolitis, Pseudomembranous/drug therapy/*microbiology/*therapy ; *Feces ; Fidaxomicin ; Humans ; Male ; Pouchitis/drug therapy/*microbiology/*therapy ; Rifamycins/pharmacology/therapeutic use ; Rifaximin ; Vancomycin/pharmacology/therapeutic use ; }, }
@article {pmid24129852, year = {2013}, author = {Ebigbo, A and Messmann, H}, title = {[Challenges of Clostridium difficile infection].}, journal = {Medizinische Klinik, Intensivmedizin und Notfallmedizin}, volume = {108}, number = {8}, pages = {624-627}, pmid = {24129852}, issn = {2193-6226}, mesh = {Aminoglycosides/therapeutic use ; Biodiversity ; Cause of Death ; Colonoscopy ; Cross Infection/diagnosis/mortality/*therapy ; Disinfection ; Enterocolitis, Pseudomembranous/diagnosis/mortality/*therapy ; Feces/microbiology ; Fidaxomicin ; Hospital Mortality ; Humans ; Metronidazole/therapeutic use ; Patient Readmission ; Prognosis ; Recurrence ; Tomography, X-Ray Computed ; Transplantation ; Vancomycin/therapeutic use ; }, abstract = {Clostridium difficile infections remain a problem especially for patients in the intensive care unit. The fact that C. difficile infections are strongly associated with antibiotic therapy calls for more caution in the use of antibiotics, especially in patients with a high risk of developing C. difficle infections. Severe infections and recurrent episodes are usually difficult to manage and therapeutic options are often limited. The method of stool transplantation, though not new, has received more attention in recent years, with studies showing stool transplantation to be a promising and easy method which has high clinical cure rates even for recurrent C. difficile infections. However, more randomised and controlled trials are needed to further study the efficacy of stool transplantation in patients with C. difficile infection.}, }
@article {pmid24123928, year = {2014}, author = {Unzueta, A and Rakela, J}, title = {Hepatitis E infection in liver transplant recipients.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {20}, number = {1}, pages = {15-24}, doi = {10.1002/lt.23764}, pmid = {24123928}, issn = {1527-6473}, mesh = {Animals ; Chronic Disease ; Disease Progression ; Feces ; Fibrosis/etiology ; Food Microbiology ; Hepatitis E/*complications/*therapy ; Humans ; Immunosuppression Therapy ; Interferons/therapeutic use ; Liver/injuries ; Liver Failure/*complications/virology ; Liver Transplantation/*adverse effects ; RNA, Viral/analysis/blood ; Ribavirin/therapeutic use ; }, abstract = {Hepatitis E virus (HEV) infection (genotype 3) has been described in developed countries as a cause of chronic hepatitis in recipients of solid organ transplantation (SOT), with the first cases reported in 2008. Immunosuppression seems to play a major role in the pathogenesis of chronic infections. The current gold standard for the diagnosis of HEV infection is the detection of HEV RNA in serum, stools, or both. In liver transplant recipients, HEV infection is considered an uncommon disease; however, a high index of suspicion is needed for patients with graft hepatitis of an unclear etiology. Liver transplant recipients seem more likely to develop chronic HEV after an acute infection, and there is accelerated progression to advanced fibrosis and cirrhosis. A decrease in immunosuppression is considered the first line of treatment, and pegylated interferon can be considered the second line of treatment for liver transplant recipients. At the present time, there are not enough data to recommend treatment with ribavirin for adult liver transplant recipients, although this has been tried in other SOT populations.}, }
@article {pmid24119331, year = {2014}, author = {Brown, AC}, title = {Ulcerative colitis, Crohn's disease and irritable bowel syndrome patients need fecal transplant research and treatment.}, journal = {Journal of Crohn's &amp; colitis}, volume = {8}, number = {2}, pages = {179}, doi = {10.1016/j.crohns.2013.09.011}, pmid = {24119331}, issn = {1876-4479}, mesh = {Colitis, Ulcerative/*therapy ; Crohn Disease/*therapy ; *Feces ; Humans ; Irritable Bowel Syndrome/*therapy ; }, }
@article {pmid24118601, year = {2014}, author = {Debast, SB and Bauer, MP and Kuijper, EJ and , }, title = {European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {20 Suppl 2}, number = {}, pages = {1-26}, doi = {10.1111/1469-0691.12418}, pmid = {24118601}, issn = {1469-0691}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*drug therapy/*microbiology ; Diarrhea/*drug therapy/*microbiology ; Enterocolitis, Pseudomembranous/*drug therapy/*microbiology ; Humans ; }, abstract = {In 2009 the first European Society of Clinical Microbiology and Infection (ESCMID) treatment guidance document for Clostridium difficile infection (CDI) was published. The guideline has been applied widely in clinical practice. In this document an update and review on the comparative effectiveness of the currently available treatment modalities of CDI is given, thereby providing evidence-based recommendations on this issue. A computerized literature search was carried out to investigate randomized and non-randomized trials investigating the effect of an intervention on the clinical outcome of CDI. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The ESCMID and an international team of experts from 11 European countries supported the process. To improve clinical guidance in the treatment of CDI, recommendations are specified for various patient groups, e.g. initial non-severe disease, severe CDI, first recurrence or risk for recurrent disease, multiple recurrences and treatment of CDI when oral administration is not possible. Treatment options that are reviewed include: antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, and faecal or bacterial intestinal transplantation. Except for very mild CDI that is clearly induced by antibiotic usage antibiotic treatment is advised. The main antibiotics that are recommended are metronidazole, vancomycin and fidaxomicin. Faecal transplantation is strongly recommended for multiple recurrent CDI. In case of perforation of the colon and/or systemic inflammation and deteriorating clinical condition despite antibiotic therapy, total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended.}, }
@article {pmid24112637, year = {2013}, author = {Di Saverio, S and Coccolini, F and Galati, M and Smerieri, N and Biffl, WL and Ansaloni, L and Tugnoli, G and Velmahos, GC and Sartelli, M and Bendinelli, C and Fraga, GP and Kelly, MD and Moore, FA and Mandalà, V and Mandalà, S and Masetti, M and Jovine, E and Pinna, AD and Peitzman, AB and Leppaniemi, A and Sugarbaker, PH and Goor, HV and Moore, EE and Jeekel, J and Catena, F}, title = {Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO): 2013 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group.}, journal = {World journal of emergency surgery : WJES}, volume = {8}, number = {1}, pages = {42}, pmid = {24112637}, issn = {1749-7922}, abstract = {BACKGROUND: In 2013 Guidelines on diagnosis and management of ASBO have been revised and updated by the WSES Working Group on ASBO to develop current evidence-based algorithms and focus indications and safety of conservative treatment, timing of surgery and indications for laparoscopy.<br><br>RECOMMENDATIONS: In absence of signs of strangulation and history of persistent vomiting or combined CT-scan signs (free fluid, mesenteric edema, small-bowel feces sign, devascularization) patients with partial ASBO can be managed safely with NOM and tube decompression should be attempted. These patients are good candidates for Water-Soluble-Contrast-Medium (WSCM) with both diagnostic and therapeutic purposes. The radiologic appearance of WSCM in the colon within 24 hours from administration predicts resolution. WSCM maybe administered either orally or via NGT both immediately at admission or after failed conservative treatment for 48 hours. The use of WSCM is safe and reduces need for surgery, time to resolution and hospital stay.NOM, in absence of signs of strangulation or peritonitis, can be prolonged up to 72 hours. After 72 hours of NOM without resolution, surgery is recommended.Patients treated non-operatively have shorter hospital stay, but higher recurrence rate and shorter time to re-admission, although the risk of new surgically treated episodes of ASBO is unchanged. Risk factors for recurrences are age <40 years and matted adhesions. WSCM does not decrease recurrence rates or recurrences needing surgery.Open surgery is often used for strangulating ASBO as well as after failed conservative management. In selected patients and with appropriate skills, laparoscopic approach is advisable using open access technique. Access in left upper quadrant or left flank is the safest and only completely obstructing adhesions should be identified and lysed with cold scissors. Laparoscopic adhesiolysis should be attempted preferably if first episode of SBO and/or anticipated single band. A low threshold for open conversion should be maintained.Peritoneal adhesions should be prevented. Hyaluronic acid-carboxycellulose membrane and icodextrin decrease incidence of adhesions. Icodextrin may reduce the risk of re-obstruction. HA cannot reduce need of surgery.Adhesions quantification and scoring maybe useful for achieving standardized assessment of adhesions severity and for further research in diagnosis and treatment of ASBO.}, }
@article {pmid24108617, year = {2013}, author = {Legoff, J and Feghoul, L and Mercier-Delarue, S and Dalle, JH and Scieux, C and Chérot, J and de Fontbrune, FS and Baruchel, A and Socié, G and Simon, F}, title = {Broad-range PCR-electrospray ionization mass spectrometry for detection and typing of adenovirus and other opportunistic viruses in stem cell transplant patients.}, journal = {Journal of clinical microbiology}, volume = {51}, number = {12}, pages = {4186-4192}, pmid = {24108617}, issn = {1098-660X}, mesh = {Adenoviridae Infections/*diagnosis/virology ; Adenoviruses, Human/classification/genetics/*isolation &amp; purification ; Adult ; Child ; Child, Preschool ; Feces/virology ; Genotype ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Molecular Diagnostic Techniques/*methods ; Plasma/virology ; Polymerase Chain Reaction/*methods ; Spectrometry, Mass, Electrospray Ionization/*methods ; *Transplantation ; }, abstract = {Hematopoietic stem cell transplant patients are highly susceptible to viral infections. Follow-up after transplantation includes weekly screening using single, virus-specific real-time PCR tests, mainly for viruses in the families Herpesviridae and Adenoviridae that contribute to a high morbidity, especially in pediatric populations. The Abbott PLEX-ID platform combines broad-range PCR with electrospray ionization mass spectrometry to enable the simultaneous detection of multiple pathogens in a single assay. The Viral IC Spectrum assay detects human adenoviruses, viruses from the family Herpesviridae (herpes simplex virus 1 [HSV-1], HSV-2, cytomegalovirus [CMV], Epstein-Barr virus [EBV], varicella-zoster virus [VZV], and human herpesvirus 8 [HHV-8]), human enterovirus, polyomaviruses (BK and JC), and parvovirus B19. We evaluated the performance of the Viral IC Spectrum assay with samples from 16 adult and 36 pediatric stem cell transplant patients. The sensitivity of the Viral IC Spectrum assay compared to real-time PCR quantification using the adenovirus Rgene kit for the detection of adenovirus was 96.7% from plasma samples (n = 92) and 78% from stool samples (n = 100). No adenovirus was detected in samples from noninfected patients (n = 30). PLEX-ID species identification was perfectly concordant with species-specific real-time PCR assays. In plasma and stool samples, the level of amplified products measured by PLEX-ID and the quantity in copies/ml (r = 0.82 and 0.78, respectively) were correlated up to 6 log10 copies/ml. In 67.4% of adenovirus-positive plasma samples, at least one other viral infection was detected; these included BK virus (n = 41), CMV (n = 30), EBV (n = 26), JC virus (n = 9), and HSV-1 (n = 6). The results of this study suggest that the Viral IC Spectrum assay performed on the PLEX-ID platform is reliable for adenovirus infection diagnosis in immunocompromised patients.}, }
@article {pmid24107393, year = {2014}, author = {Kelly, CR and Kunde, SS and Khoruts, A}, title = {Guidance on preparing an investigational new drug application for fecal microbiota transplantation studies.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {12}, number = {2}, pages = {283-288}, pmid = {24107393}, issn = {1542-7714}, support = {R21 AI091907/AI/NIAID NIH HHS/United States ; R21 DK093839/DK/NIDDK NIH HHS/United States ; R21AI091907/AI/NIAID NIH HHS/United States ; 1R21DK093839-01A1/DK/NIDDK NIH HHS/United States ; }, mesh = {Biological Therapy/*methods ; Clinical Protocols ; Clostridioides difficile ; Enterocolitis, Pseudomembranous ; Feces/*microbiology ; Humans ; Intestines/microbiology ; *Investigational New Drug Application/organization &amp; administration ; *Microbiota ; Recurrence ; Specimen Handling ; Transplantation/methods ; United States ; United States Food and Drug Administration ; }, abstract = {Fecal microbiota transplantation (FMT) is an effective treatment for Clostridium difficile infections that are refractory to antibiotic therapy. Because of the important roles of the microbiota in the function of the gastrointestinal tract and other aspects of human physiology, there is a growing interest in studying FMT for other clinical indications. The US Food and Drug Administration regulates clinical studies to evaluate the safety and efficacy of FMT. Studies of FMT for recurrent Clostridium difficile infection or other indications could require submission of an investigational new drug application. Most academic physicians and investigators do not have the regulatory experience necessary to undertake this process. We provide guidance to researchers on the preparation and submission of investigational new drug applications to study FMT.}, }
@article {pmid24103787, year = {2014}, author = {Bordes, J and Le Floch, R and Bourdais, L and Gamelin, A and Lebreton, F and Perro, G}, title = {Perineal burn care: French working group recommendations.}, journal = {Burns : journal of the International Society for Burn Injuries}, volume = {40}, number = {4}, pages = {655-663}, doi = {10.1016/j.burns.2013.09.007}, pmid = {24103787}, issn = {1879-1409}, mesh = {Burns/*therapy ; *Catheters ; *Colostomy ; Feces ; France ; Graft Survival ; Humans ; Perineum/*injuries ; Skin Transplantation ; Wound Healing ; Wound Infection/*prevention &amp; control ; }, abstract = {OBJECTIVES: Burns to the perineum are frequently exposed to faeces. Diverting colostomy is often described to prevent faecal soiling. Because this technique is invasive with frequent complications, use of non-surgical devices including specifically designed faecal management systems has been reported in perineal burns.<br><br>METHODS: In order to standardise the faecal management strategy in patients with perineal burns, a group of French experts was assembled. This group first evaluated the ongoing practice in France by analysing a questionnaire sent to every French burn centre. Based on the results of this study and on literature data, the experts proposed recommendations on the management of perineal burns in adults.<br><br>RESULTS: Specifically designed faecal management systems are the first-line method to divert faeces in perineal burns. The working group proposed recommendations and an algorithm to assist in decisions in the management of perineal burns in four categories of patients, depending on total burn skin area, depth and extent of the perineal burn.<br><br>CONCLUSION: In France, non-surgical devices are the leading means of faecal diversion in perineal burns. The proposed algorithm may assist in decisions in the management of perineal burns. The expert group emphasises that large clinical studies are needed to better evaluate these devices.}, }
@article {pmid24102954, year = {2013}, author = {Altomare, DF and Giannini, I and Giuratrabocchetta, S and Digennaro, R}, title = {The effects of sacral nerve stimulation on continence are temporarily maintained after turning the stimulator off.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {15}, number = {12}, pages = {e741-8}, doi = {10.1111/codi.12418}, pmid = {24102954}, issn = {1463-1318}, mesh = {Adult ; Aged ; Anal Canal/*innervation/physiopathology ; Cohort Studies ; Electric Stimulation Therapy/*methods ; Electrodes, Implanted ; Fecal Incontinence/complications/*therapy ; Female ; Humans ; *Lumbosacral Plexus ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Urinary Incontinence/complications/*therapy ; }, abstract = {AIM: Sacral nerve stimulation is an effective treatment for urinary and faecal incontinence even though its mechanism of action is uncertain. Central nervous system involvement by 'setting-up' neurological mechanisms appointed to control pelvic function has been hypothesized. The study aimed to evaluate whether the effects of long-term sacral nerve stimulation are memorized and therefore maintained after switching off the stimulator.<br><br>METHOD: Patients having sacral nerve stimulation for faecal and/or urinary incontinence for at least 1&#xa0;year had the stimulator turned off and the results monitored. Data recorded with the stimulator off were compared with post-implant data. If symptoms recurred the stimulator was switched back on. Nineteen patients entered the study. Fourteen had faecal and/or urinary incontinence and five had faecal incontinence alone. The symptoms were assessed by means of a bowel function diary and dedicated questionnaire.<br><br>RESULTS: In 10 patients symptoms recurred at different intervals after a median off period of 3.4&#xa0;months with a probability of symptom relapse of 55%. The Fecal Incontinence Quality of Life (FIQL) score did not show any significant difference in nine patients with the stimulator off for at least 1&#xa0;year. No factors predictive of symptom recurrence were identified although an idiopathic aetiology, severity of disease and urinary incontinence had higher hazard ratios. During the off period, none of the scores and episodes of incontinence showed significant changes compared with the on period.<br><br>CONCLUSION: The effects of sacral nerve stimulation on faecal and urinary incontinence were maintained in about half of patients after switching the stimulator off, but in some symptoms returned after different periods of time. The data shed new light on possible effects of sacral nerve stimulation on brain neuroplasticity in the control of continence.}, }
@article {pmid24100717, year = {2013}, author = {Koenigsknecht, MJ and Young, VB}, title = {Faecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection: current promise and future needs.}, journal = {Current opinion in gastroenterology}, volume = {29}, number = {6}, pages = {628-632}, pmid = {24100717}, issn = {1531-7056}, support = {T32 AI007528/AI/NIAID NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; }, mesh = {Biological Therapy/adverse effects/*methods/standards ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Humans ; Intestines/microbiology ; *Microbiota ; Randomized Controlled Trials as Topic ; Recurrence ; }, abstract = {PURPOSE OF REVIEW: The use of faecal microbiota transplantation (FMT) as treatment for recurrent Clostridium difficile infection (CDI) has increased rapidly over the past few years. In this review, we highlight clinical studies of FMT for treatment of recurrent CDI and discuss the safety, standardization and future of this treatment option. The major risk factor for CDI is prior antibiotic use, which results in an altered state of the gut microbiota characterized by decreased microbial diversity. This altered gut microbiota increases the patient's susceptibility to CDI. In patients with recurrent CDI, the microbiota remains in a state with decreased diversity, and FMT from a healthy individual restores the gut microbiota and subsequently colonization resistance against the pathogen.<br><br>RECENT FINDINGS: Recent studies have shown the success rate for FMT as treatment for recurrent CDI being greater than 90%. Standardized, frozen preparations of faeces can be used, which increases the availability of faeces for FMT and decreases the cost of screening individual donors. In addition, there have been recent advances in identifying a defined microbial community isolated from faeces that can restore colonization resistance against C. difficile.<br><br>SUMMARY: The use of FMT is a successful treatment for recurrent CDI when primary treatment options have failed. However, more work needs to define potential long-term consequences of this treatment and understand how specific members of the gut microbiota can restore colonization resistance against C. difficile.}, }
@article {pmid24098410, year = {2013}, author = {Ren, Z and Cui, G and Lu, H and Chen, X and Jiang, J and Liu, H and He, Y and Ding, S and Hu, Z and Wang, W and Zheng, S}, title = {Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats through 16s rDNA-based analysis of microbial structure shift.}, journal = {PloS one}, volume = {8}, number = {10}, pages = {e75950}, pmid = {24098410}, issn = {1932-6203}, mesh = {Animals ; Cluster Analysis ; DNA, Ribosomal/*genetics ; Feces/microbiology ; Intestines/*microbiology ; *Ischemic Preconditioning ; Liver/*blood supply ; *Liver Transplantation ; *Microbiota ; Phylogeny ; Rats ; }, abstract = {BACKGROUND: Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The "gut-liver axis" closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT).<br><br>METHODS: The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-&#x3b1;. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis.<br><br>PRINCIPAL FINDINGS: Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-&#x3b1; decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum.<br><br>CONCLUSION: Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the "gut-liver axis".}, }
@article {pmid24091517, year = {2013}, author = {Sofi, AA and Georgescu, C and Sodeman, T and Nawras, A}, title = {Physician outlook toward fecal microbiota transplantation in the treatment of Clostridium difficile infection.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {10}, pages = {1661-1662}, doi = {10.1038/ajg.2013.207}, pmid = {24091517}, issn = {1572-0241}, mesh = {*Attitude of Health Personnel ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Gastroenterology/methods ; Humans ; Infectious Disease Medicine/methods ; Male ; *Metagenome ; Surveys and Questionnaires ; *Transplantation ; }, }
@article {pmid24091514, year = {2013}, author = {Brandt, LJ}, title = {Response to Gutman and Kurchin: we are not cisterns made for hoarding.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {10}, pages = {1660}, doi = {10.1038/ajg.2013.225}, pmid = {24091514}, issn = {1572-0241}, mesh = {*Enema ; Enterocolitis/*microbiology/*therapy ; *Feces ; Humans ; Intestines/*microbiology ; *Metagenome ; *Transplantation, Homologous ; }, }
@article {pmid24091513, year = {2013}, author = {Gutman, J and Kurchin, A}, title = {Split donation fecal microbiota transplantation.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {10}, pages = {1659-1660}, doi = {10.1038/ajg.2013.224}, pmid = {24091513}, issn = {1572-0241}, mesh = {*Enema ; Enterocolitis/*microbiology/*therapy ; *Feces ; Humans ; Intestines/*microbiology ; *Metagenome ; *Transplantation, Homologous ; }, }
@article {pmid24091506, year = {2013}, author = {Rubin, DT}, title = {Curbing our enthusiasm for fecal transplantation in ulcerative colitis.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {10}, pages = {1631-1633}, doi = {10.1038/ajg.2013.279}, pmid = {24091506}, issn = {1572-0241}, mesh = {Colitis, Ulcerative/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Metagenome/*genetics ; RNA, Ribosomal, 16S/*analysis ; *Transplantation ; }, abstract = {Given the known dysbiosis of gut microflora in inflammatory bowel disease, there has been great enthusiasm about the potential for fecal microbiota transplantation (FMT) as a treatment. This editorial accompanies a prospective series of five patients with ulcerative colitis who underwent FMT, but did not achieve remission. I discuss the important observations from this study and point out that the lack of clinical efficacy and observed side effects warrant caution in the ongoing pursuit of this treatment option.}, }
@article {pmid24070153, year = {2013}, author = {Vindigni, SM and Broussard, EK and Surawicz, CM}, title = {Alteration of the intestinal microbiome: fecal microbiota transplant and probiotics for Clostridium difficile and beyond.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {7}, number = {7}, pages = {615-628}, doi = {10.1586/17474124.2013.832501}, pmid = {24070153}, issn = {1747-4132}, mesh = {Animals ; Biological Therapy/*methods ; Clostridioides difficile/*pathogenicity ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*therapy ; Feces/*microbiology ; Humans ; Intestines/*microbiology ; Microbiota ; Probiotics/*therapeutic use ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridium difficile infection is increasingly common with a high risk of recurrence despite antibiotic treatment. In cases of recurrent C. difficile infection, fecal microbiota transplant (FMT) is a highly effective treatment option promoting the restoration of normal gut microbiota. Furthermore, preliminary uncontrolled evidence demonstrates possible benefit of FMT in the management of some cases of inflammatory bowel disease and chronic constipation. In addition to presenting an overview of FMT, we discuss the role of probiotics, a more common approach to modifying the intestinal microbiome. Probiotics have been utilized broadly for many disease processes, including gastrointestinal, cardiovascular and allergic disease settings, although with limited and inconsistent results. Multiple potential areas for research are also identified.}, }
@article {pmid24067112, year = {2013}, author = {Habib, SM and Dor, FJ and Korte, MR and Hagen, SM and Betjes, MG}, title = {Post-transplantation encapsulating peritoneal sclerosis without inflammation or radiological abnormalities.}, journal = {BMC nephrology}, volume = {14}, number = {}, pages = {203}, pmid = {24067112}, issn = {1471-2369}, mesh = {Diagnosis, Differential ; Female ; Humans ; Intestinal Obstruction/*diagnosis/*etiology/surgery ; Kidney Transplantation/*adverse effects ; Middle Aged ; Nephritis/diagnostic imaging/etiology ; Peritoneal Fibrosis/*diagnosis/*etiology/surgery ; Radiography ; Treatment Outcome ; }, abstract = {BACKGROUND: Post-transplantation encapsulating peritoneal sclerosis (EPS) causing bowel obstruction has been identified as a serious complication after kidney transplantation in patients previously treated with peritoneal dialysis. Systemic inflammation and abnormalities on an abdominal computed tomography (CT) scan are important hallmarks of EPS. To our knowledge, this is the first report of a case being diagnosed with late-onset post-transplantation EPS without systemic inflammation or abnormalities on a CT scan which could only be diagnosed by laparotomy.<br><br>CASE PRESENTATION: A 59-year old female presented because of symptoms of bowel obstruction 33 months after kidney transplantation. The patient had a 26-month history of peritoneal dialysis before her first kidney transplantation and was treated with peritoneal dialysis for 4 years before undergoing a second kidney transplantation. Physical examination was unremarkable and laboratory tests showed no signs of systemic inflammation (C-reactive protein <1 mg/L). An abdominal CT scan did not reveal any abnormalities fitting the diagnosis of EPS, except a "feces sign". Given the severity of the progressive symptoms, a diagnostic laparotomy was performed, visualizing a classical EPS. Total peritonectomy and enterolysis were performed, leading to restoration of peristalsis.<br><br>CONCLUSION: EPS may occur several years after kidney transplantation in the absence of inflammation and typical radiological abnormalities. Obtaining a diagnosis of post-transplantation EPS is challenging, however, a low threshold for surgical exploration in case of high clinical suspicion and negative findings on the CT scan is mandatory.}, }
@article {pmid24066468, year = {2013}, author = {Hiroz, P and Gouttenoire, J and Dao Thi, VL and Sahli, R and Telenti, A and Moradpour, D and Doerig, C}, title = {[An update on hepatitis E].}, journal = {Revue medicale suisse}, volume = {9}, number = {396}, pages = {1594, 1596-8}, pmid = {24066468}, issn = {1660-9379}, mesh = {Adolescent ; Adult ; Age Factors ; Antiviral Agents/*therapeutic use ; Female ; Genotype ; Hepatitis E/epidemiology/*therapy/virology ; Hepatitis E virus/genetics/*isolation &amp; purification ; Humans ; *Immunocompromised Host ; Male ; Middle Aged ; Risk Factors ; Seroepidemiologic Studies ; Sex Factors ; Switzerland/epidemiology ; Young Adult ; }, abstract = {The hepatitis E virus (HEV) is an RNA virus transmitted via the fecal-oral route or through uncooked animal meat products. Of the 4 known genotypes, genotype 3 is responsible for autochthonous infections in industrialized countries, with a seroprevalence in Switzerland estimated as high as 22%. The majority of infections is asymptomatic but a minority of patients, notably men over 50 or with underlying liver disease, can present with severe acute hepatitis. Chronic hepatitis E with HEV of genotype 3 has been observed in immunosuppressed patients, mostly transplant recipients. Serology is not sufficiently sensitive, especially in immunosuppressed patients, making PCR identification the preferred test for diagnosing active infection. Ribavirin or interferon-alpha can be used to treat chronic hepatitis E if reduction of immunosuppressive treatment does not result in viral elimination.}, }
@article {pmid24060759, year = {2013}, author = {Angelberger, S and Reinisch, W and Makristathis, A and Lichtenberger, C and Dejaco, C and Papay, P and Novacek, G and Trauner, M and Loy, A and Berry, D}, title = {Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {10}, pages = {1620-1630}, doi = {10.1038/ajg.2013.257}, pmid = {24060759}, issn = {1572-0241}, mesh = {Adult ; Bacteroides/genetics ; C-Reactive Protein ; Clostridium/genetics ; Colitis, Ulcerative/microbiology/*therapy ; Enema ; Enterobacteriaceae/genetics ; Feces/*microbiology ; Female ; Humans ; Intubation, Gastrointestinal ; Male ; Metagenome/*genetics ; Middle Aged ; RNA, Ribosomal, 16S/*analysis ; Time Factors ; *Transplantation ; Young Adult ; }, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) from healthy donors, which is an effective alternative for treatment of Clostridium difficile-associated disease, is being considered for several disorders such as inflammatory bowel disease, irritable bowel syndrome, and metabolic syndrome. Disease remission upon FMT is thought to be facilitated by an efficient colonization of healthy donor microbiota, but knowledge of the composition and temporal stability of patient microbiota after FMT is lacking.<br><br>METHODS: Five patients with moderately to severely active ulcerative colitis (Mayo score &#x2265;6) and refractory to standard therapy received FMT via nasojejunal tube and enema. In addition to clinical activity and adverse events, the patients' fecal bacterial communities were monitored at multiple time points for up to 12 weeks using 16S rRNA gene-targeted pyrosequencing.<br><br>RESULTS: FMT elicited fever and a temporary increase of C-reactive protein. Abundant bacteria from donors established in recipients, but the efficiency and stability of donor microbiota colonization varied greatly. A positive clinical response was observed after 12 weeks in one patient whose microbiota had been effectively augmented by FMT. This augmentation was marked by successive colonization of donor-derived phylotypes including the anti-inflammatory and/or short-chain fatty acid-producing Faecalibacterium prausnitzii, Rosebura faecis, and Bacteroides ovatus. Disease severity (as measured by the Mayo score) was associated with an overrepresentation of Enterobacteriaceae and an underrepresentation of Lachnospiraceae.<br><br>CONCLUSIONS: This study highlights the value of characterizing temporally resolved microbiota dynamics for a better understanding of FMT efficacy and provides potentially useful diagnostic indicators for monitoring FMT success in the treatment of ulcerative colitis.}, }
@article {pmid24055638, year = {2013}, author = {Sampath, K and Levy, LC and Gardner, TB}, title = {Fecal transplantation: beyond the aesthetic.}, journal = {Gastroenterology}, volume = {145}, number = {5}, pages = {1151-1153}, doi = {10.1053/j.gastro.2013.09.015}, pmid = {24055638}, issn = {1528-0012}, mesh = {Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile ; Diarrhea/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Vancomycin/*therapeutic use ; }, }
@article {pmid24054811, year = {2013}, author = {Gareau, MG and Barrett, KE}, title = {Fluid and electrolyte secretion in the inflamed gut: novel targets for treatment of inflammation-induced diarrhea.}, journal = {Current opinion in pharmacology}, volume = {13}, number = {6}, pages = {895-899}, doi = {10.1016/j.coph.2013.08.014}, pmid = {24054811}, issn = {1471-4973}, mesh = {Animals ; Bacterial Infections/physiopathology ; Diarrhea/metabolism/microbiology/*physiopathology ; Electrolytes/*metabolism ; Gastrointestinal Tract/metabolism/microbiology/*physiopathology ; Humans ; Inflammation/metabolism/*physiopathology ; Ion Transport/*physiology ; }, abstract = {Diarrheal disease can occur in the context of both inflammatory and infectious challenges. Inflammation can result in changes in ion transporter expression or simply mislocalization of the protein. In addition to development of diarrhea, an altered secretory state can lead to changes in mucus secretion and luminal pH. Bacterial infection can lead to subversion of host cell signaling, leading to transporter mislocalization and hyposecretion, promoting bacterial colonization. Novel therapeutic strategies are currently being developed to ameliorate transporter defects in the setting of inflammation or bacterial infection including, for example, administration of probiotics and fecal microbiota transplantation. This review will highlight recent findings in the literature detailing these aspects of ion transport in the inflamed gut.}, }
@article {pmid24053182, year = {2013}, author = {Tran, MC and Claros, MC and Goldstein, EJ}, title = {Therapy of Clostridium difficile infection: perspectives on a changing paradigm.}, journal = {Expert opinion on pharmacotherapy}, volume = {14}, number = {17}, pages = {2375-2386}, doi = {10.1517/14656566.2013.838218}, pmid = {24053182}, issn = {1744-7666}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile ; Clostridium Infections/*drug therapy ; Humans ; }, abstract = {INTRODUCTION: Clostridium difficile disease (CDI) have increased in frequency and severity over the past decade and are a leading cause of hospital acquired infections, contributing to increased hospital length of stay and costs, as well as associated increased mortality, especially amongst the elderly. Standard therapy has been associated with 20 - 30% relapse rates. Consequently, new CDI therapeutic approaches have emerged.<br><br>AREAS COVERED: The role of metronidazole, vancomycin, fidaxomicin, rifaximin, nitizoxanide, tigecycline, fusidic acid, LFF-571, cardazolid, SMT 19969, CamSA and surotomycin were reviewed.<br><br>EXPERT OPINION: New IDSA/SHEA guidelines are expected within the next year and may impact selection of primary therapy for CDI. Until then, metronidazole will likely remain as first line therapy because of low cost and despite its inferiority compared to vancomycin. Vancomycin will likely see increasing use, especially as generics become available. Fidaxomicin will emerge as an important therapy for relapse patients and perhaps as initial therapy for patients at greatest risk for relapse, with concomitant antibiotics, multiple comorbidities and renal insufficiency, advanced age and hypoalbuminemia. Biotherapeutics such as fecal microbiota transplantation and non-toxogenic C. difficile prevention will emerge as the preferred therapy in multiple relapse patients and the development of an oral formulation will occur within five years.}, }
@article {pmid24049940, year = {2013}, author = {Paasché, S}, title = {Fecal microbiota transplantation: an innovative approach to treating Clostridium difficile disease.}, journal = {JAAPA : official journal of the American Academy of Physician Assistants}, volume = {26}, number = {8}, pages = {46-49}, doi = {10.1097/01.jaa.0000432570.98817.16}, pmid = {24049940}, issn = {1547-1896}, mesh = {Biological Therapy/*methods ; Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; }, abstract = {Normal gut flora or microbiota, which is key to a healthy digestive tract, can be disrupted by antibiotic therapy, potentially leading to Clostridium difficile-associated disease (CDAD). Fecal microbiota transplant has shown promise in quickly and safely eradicating CDAD at low cost.}, }
@article {pmid24047954, year = {2013}, author = {Campanini, G and Rovida, F and Meloni, F and Cascina, A and Ciccocioppo, R and Piralla, A and Baldanti, F}, title = {Persistent human cosavirus infection in lung transplant recipient, Italy.}, journal = {Emerging infectious diseases}, volume = {19}, number = {10}, pages = {1667-1669}, pmid = {24047954}, issn = {1080-6059}, mesh = {Adult ; Diarrhea/*diagnosis/virology ; Feces/virology ; Female ; Humans ; Italy ; *Lung Transplantation ; Molecular Typing ; Picornaviridae/*genetics ; Picornaviridae Infections/*diagnosis/virology ; Sequence Analysis, DNA ; Transplantation ; Viral Structural Proteins/genetics ; }, abstract = {Human cosavirus is a novel picornavirus recently identified in feces from children in southern Asia. We report infection with human cosavirus in a patient in the Mediterranean area. The patient was an adult double lung transplant recipient who had chronic diarrhea associated with persistent infection with human cosavirus.}, }
@article {pmid24018052, year = {2013}, author = {Smits, LP and Bouter, KE and de Vos, WM and Borody, TJ and Nieuwdorp, M}, title = {Therapeutic potential of fecal microbiota transplantation.}, journal = {Gastroenterology}, volume = {145}, number = {5}, pages = {946-953}, doi = {10.1053/j.gastro.2013.08.058}, pmid = {24018052}, issn = {1528-0012}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; Inflammatory Bowel Diseases/*therapy ; *Microbiota ; Transplantation, Homologous ; *Transplants ; Treatment Outcome ; }, abstract = {There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections and inflammatory bowel diseases. Lately, there has also been interest in its therapeutic potential for cardiometabolic, autoimmune, and other extraintestinal conditions that were not previously considered to be associated with the intestinal microbiota. Although it is not clear if changes in the microbiota cause these conditions, we review the most current and best methods for performing fecal microbiota transplantation and summarize clinical observations that have implicated the intestinal microbiota in various diseases. We also discuss case reports of fecal microbiota transplantations for different disorders, including Clostridium difficile infection, irritable bowel syndrome, inflammatory bowel diseases, insulin resistance, multiple sclerosis, and idiopathic thrombocytopenic purpura. There has been increasing focus on the interaction between the intestinal microbiome, obesity, and cardiometabolic diseases, and we explore these relationships and the potential roles of different microbial strains. We might someday be able to mine for intestinal bacterial strains that can be used in the diagnosis or treatment of these diseases.}, }
@article {pmid24012982, year = {2014}, author = {Brenner, H and Chang-Claude, J and Jansen, L and Knebel, P and Stock, C and Hoffmeister, M}, title = {Reduced risk of colorectal cancer up to 10 years after screening, surveillance, or diagnostic colonoscopy.}, journal = {Gastroenterology}, volume = {146}, number = {3}, pages = {709-717}, doi = {10.1053/j.gastro.2013.09.001}, pmid = {24012982}, issn = {1528-0012}, mesh = {Aged ; Aged, 80 and over ; Case-Control Studies ; *Colonoscopy ; Colorectal Neoplasms/*diagnosis/*epidemiology/pathology ; *Early Detection of Cancer ; Educational Status ; *Epidemiological Monitoring ; Female ; Germany ; Humans ; Logistic Models ; Longitudinal Studies ; Male ; Middle Aged ; Risk Factors ; Smoking/adverse effects ; Social Class ; }, abstract = {BACKGROUND &amp; AIMS: Data from randomized controlled trials on the effects of screening colonoscopies on colorectal cancer (CRC) incidence and mortality are not available. Observational studies have suggested that colonoscopies strongly reduce the risk of CRC, but there is little specific evidence on the effects of screening colonoscopies.<br><br>METHODS: We performed a population-based case-control study of 3148 patients with a first diagnosis of CRC (cases) and 3274 subjects without CRC (controls) from the Rhine-Neckar region of Germany from 2003 to 2010. Detailed information on previous colonoscopy and potential confounding factors was collected by standardized personal interviews. Self-reported information on colonoscopies and their indications was validated by medical records. We used multiple logistic regression to assess the association between colonoscopy conducted for specific indications within the past 10 years and risk of CRC.<br><br>RESULTS: A history of colonoscopy was associated with a reduced subsequent risk of CRC, independently of the indication for the examination. However, somewhat stronger associations were found for examinations with screening indications (adjusted odds ratio [OR] 0.09, 95% confidence interval [CI] 0.07-0.13) than for examinations with diagnostic indications, such as positive fecal occult blood test result (OR, 0.33; 95% CI, 0.19-0.57), surveillance after a preceding colonoscopy (OR, 0.33; 95% CI, 0.24-0.45), rectal bleeding (OR, 0.28; 95% CI, 0.20-0.40), abdominal symptoms (OR, 0.15; 95% CI, 0.10-0.21), or other (OR, 0.21; 95% CI, 0.14-0.30). Colonoscopy was also associated with a reduced risk of cancer in the right colon, regardless of the indication, although to a smaller extent than for other areas of the colon (OR for screening colonoscopy, 0.22; 95% CI, 0.14-0.33).<br><br>CONCLUSIONS: In a population-based case-control study, the risk of CRC was strongly reduced up to 10 years after colonoscopy for any indication. Risk was particularly low after screening colonoscopy, even for cancer in the right colon.}, }
@article {pmid24012687, year = {2013}, author = {Bakken, JS and Polgreen, PM and Beekmann, SE and Riedo, FX and Streit, JA}, title = {Treatment approaches including fecal microbiota transplantation for recurrent Clostridium difficile infection (RCDI) among infectious disease physicians.}, journal = {Anaerobe}, volume = {24}, number = {}, pages = {20-24}, doi = {10.1016/j.anaerobe.2013.08.007}, pmid = {24012687}, issn = {1095-8274}, support = {1U50CK000187/CK/NCEZID CDC HHS/United States ; }, mesh = {Biological Therapy/methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Data Collection ; Diarrhea/microbiology/*therapy ; Humans ; Practice Patterns, Physicians'/*statistics &amp; numerical data ; Secondary Prevention ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) was the most common nosocomial infection in the U.S. in 2010. Most cases of CDI respond to a standard course of antibiotics, but recurrent C. difficile infections (RCDI) are increasingly common. Given the lack of randomized clinical trials, it is important to understand how infectious disease physicians are managing RCDI to inform future clinical research.<br><br>METHODS: An electronic survey was conducted among members of the Emerging Infections Network (EIN) in October 2012. Respondents were asked to answer specific questions about their treatment approaches toward patients with CDI, including fecal microbiota transplantation (FMT).<br><br>RESULTS: The overall response rate was 621/1212 (51%). The vast majority of respondents had cared for small to moderate numbers of patients with CDI over the prior 6 months, and reported recurrence rates were consistent with published data. Preferred treatment regimens for RCDI showed significant variance from recommendations published in national guidelines. Eighty percent (424/527) of the respondents would consider FMT for patients with RCDI, and of 149 who had FMT available at their institution, 107 (72%) had actually treated >1 patient with FMT in the preceding year. However, significant barriers to institutional adoption of FMT remain for many respondents, despite very good success rates with its use.<br><br>CONCLUSIONS: Physicians who regularly care for patients with CDI use a variety of treatment approaches for treating severe or recurrent CDI cases. The results of our survey demonstrate that FMT is used by a growing number of infectious disease providers as an effective and safe treatment alternative for patients with multiple recurrences of C. difficile infection.}, }
@article {pmid24012274, year = {2013}, author = {Owens, C and Broussard, E and Surawicz, C}, title = {Fecal microbiota transplantation and donor standardization.}, journal = {Trends in microbiology}, volume = {21}, number = {9}, pages = {443-445}, doi = {10.1016/j.tim.2013.07.003}, pmid = {24012274}, issn = {1878-4380}, mesh = {Biological Therapy/*standards ; Clostridioides difficile/genetics/isolation &amp; purification/*physiology ; Diarrhea/microbiology/*therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Humans ; *Microbiota ; }, abstract = {Clostridium difficile diarrhea is a common and severe infectious disease. Antibiotics, which are standard initial treatment, are less effective for treating refractory or recurrent infection. Fecal microbiota transplantation, where healthy donor stool is transplanted into a patient, is an alternative to antibiotic therapy that requires standardization for donors and patients.}, }
@article {pmid24010110, year = {2013}, author = {Kim, BS and Jeon, YS and Chun, J}, title = {Current status and future promise of the human microbiome.}, journal = {Pediatric gastroenterology, hepatology &amp; nutrition}, volume = {16}, number = {2}, pages = {71-79}, pmid = {24010110}, issn = {2234-8646}, abstract = {The human-associated microbiota is diverse, varies between individuals and body sites, and is important in human health. Microbes in human body play an essential role in immunity, health, and disease. The human microbiome has been studies using the advances of next-generation sequencing and its metagenomic applications. This has allowed investigation of the microbial composition in the human body, and identification of the functional genes expressed by this microbial community. The gut microbes have been found to be the most diverse and constitute the densest cell number in the human microbiota; thus, it has been studied more than other sites. Early results have indicated that the imbalances in gut microbiota are related to numerous disorders, such as inflammatory bowel disease, colorectal cancer, diabetes, and atopy. Clinical therapy involving modulating of the microbiota, such as fecal transplantation, has been applied, and its effects investigated in some diseases. Human microbiome studies form part of human genome projects, and understanding gleaned from studies increase the possibility of various applications including personalized medicine.}, }
@article {pmid24009397, year = {2013}, author = {Ridaura, VK and Faith, JJ and Rey, FE and Cheng, J and Duncan, AE and Kau, AL and Griffin, NW and Lombard, V and Henrissat, B and Bain, JR and Muehlbauer, MJ and Ilkayeva, O and Semenkovich, CF and Funai, K and Hayashi, DK and Lyle, BJ and Martini, MC and Ursell, LK and Clemente, JC and Van Treuren, W and Walters, WA and Knight, R and Newgard, CB and Heath, AC and Gordon, JI}, title = {Gut microbiota from twins discordant for obesity modulate metabolism in mice.}, journal = {Science (New York, N.Y.)}, volume = {341}, number = {6150}, pages = {1241214}, pmid = {24009397}, issn = {1095-9203}, support = {K01 DK095774/DK/NIDDK NIH HHS/United States ; K05 AA017688/AA/NIAAA NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P30-AG028716/AG/NIA NIH HHS/United States ; DK078669/DK/NIDDK NIH HHS/United States ; R01 DK076729/DK/NIDDK NIH HHS/United States ; DK70977/DK/NIDDK NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; F32 DK091044/DK/NIDDK NIH HHS/United States ; P01 DK078669/DK/NIDDK NIH HHS/United States ; DK58398/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; P30 DK056341/DK/NIDDK NIH HHS/United States ; P01 DK058398/DK/NIDDK NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; P30 DK020579/DK/NIDDK NIH HHS/United States ; }, mesh = {*Adiposity ; Adult ; Animals ; Bacteroidetes/genetics/*physiology ; Cecum/metabolism/microbiology ; Diet, Fat-Restricted ; Feces/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Germ-Free Life ; Humans ; Metabolome ; Metagenome/genetics/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/genetics/*metabolism ; Thinness/microbiology ; Twins ; Weight Gain ; Young Adult ; }, abstract = {The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.}, }
@article {pmid24005362, year = {2013}, author = {Baty, V and Mougin, B}, title = {What about public perception of antibiotics in the era of the fecal microbiota transplantation? Between the devil and the deep blue sea.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {9}, pages = {1540}, doi = {10.1038/ajg.2013.193}, pmid = {24005362}, issn = {1572-0241}, mesh = {*Anti-Bacterial Agents ; Feces/*microbiology ; *Health Knowledge, Attitudes, Practice ; Humans ; Metagenome ; *Perception ; }, }
@article {pmid24005359, year = {2013}, author = {Kassam, Z and Lee, CH and Yuan, Y and Hunt, RH}, title = {Navigating long-term safety in fecal microbiota transplantation.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {9}, pages = {1538}, doi = {10.1038/ajg.2013.214}, pmid = {24005359}, issn = {1572-0241}, mesh = {Biological Therapy/*methods ; Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Metagenome/*physiology ; }, }
@article {pmid24005358, year = {2013}, author = {El-Matary, W}, title = {Fecal microbiota transplantation: long-term safety issues.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {9}, pages = {1537-1538}, doi = {10.1038/ajg.2013.208}, pmid = {24005358}, issn = {1572-0241}, mesh = {Biological Therapy/*methods ; Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Metagenome/*physiology ; }, }
@article {pmid23995428, year = {2013}, author = {Davidovics, ZH and Hyams, JS}, title = {Fecal transplantation: re-discovering the value of stool.}, journal = {Current opinion in pediatrics}, volume = {25}, number = {5}, pages = {618-623}, doi = {10.1097/MOP.0b013e328363ed66}, pmid = {23995428}, issn = {1531-698X}, mesh = {Child ; Child, Preschool ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/immunology/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Inflammatory Bowel Diseases/immunology/microbiology/*therapy ; Intubation, Gastrointestinal ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: For over 1000 years, stool in various forms has been used to treat disease. Within the past few decades, fecal infusion either rectally or via a nasogastric tube has become a viable option for the treatment of refractory Clostridium difficile infection (CDI), and, more recently, it has shown promise in treating inflammatory bowel disease (IBD) and metabolic disease. The purpose of this article is to review the use of feces as a treatment option in pediatric disease.<br><br>RECENT FINDINGS: The majority of publications detailing the use of fecal infusion as a medical treatment have been case reports. In the first randomized controlled trial of its kind, fecal infusion via nasogastric tube was shown to be beneficial in treating refractory CDI in adults. In another first of its kind, a pilot study on the use of fecal enemas to treat ulcerative colitis in pediatric patients found it to be well tolerated and effective.<br><br>SUMMARY: The infusion of feces into the intestinal tract shows great promise for treatment and modulation of a variety of intestinal and extraintestinal diseases. Defining the underlying mechanism, microbes, and metabolites that mediate this effect will lead to more directed, safer, and potentially more effective treatments.}, }
@article {pmid23990541, year = {2013}, author = {de Vrieze, J}, title = {Medical research. Regulators grapple with an unorthodox therapy.}, journal = {Science (New York, N.Y.)}, volume = {341}, number = {6149}, pages = {956}, doi = {10.1126/science.341.6149.956}, pmid = {23990541}, issn = {1095-9203}, mesh = {Clostridioides difficile ; Complementary Therapies/*methods ; Enterocolitis, Pseudomembranous/therapy ; Feces/*microbiology ; Female ; Humans ; Transplantation ; United States ; United States Food and Drug Administration ; }, }
@article {pmid23990540, year = {2013}, author = {de Vrieze, J}, title = {Medical research. The promise of poop.}, journal = {Science (New York, N.Y.)}, volume = {341}, number = {6149}, pages = {954-957}, doi = {10.1126/science.341.6149.954}, pmid = {23990540}, issn = {1095-9203}, mesh = {Anti-Bacterial Agents/adverse effects ; *Clostridioides difficile ; Diarrhea/chemically induced/microbiology/therapy ; Enterocolitis, Pseudomembranous/chemically induced/*therapy ; Feces/*microbiology ; Gastrointestinal Diseases/microbiology/therapy ; Humans ; *Metagenome ; Randomized Controlled Trials as Topic ; Transplantation ; Vancomycin/adverse effects ; }, }
@article {pmid23982236, year = {2013}, author = {Martin, J and Mawer, D and Wilcox, MH}, title = {Clostridium difficile: biological therapies.}, journal = {Current opinion in infectious diseases}, volume = {26}, number = {5}, pages = {454-460}, doi = {10.1097/01.qco.0000433319.82618.8f}, pmid = {23982236}, issn = {1473-6527}, mesh = {Biological Therapy/*methods ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/microbiology ; Humans ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: Biological therapies for Clostridium difficile infection (CDI) include probiotics and faecal microbiota transplant (FMT). There is significant interest in their use in treating refractory/recurrent CDI. This review summarizes the latest evidence for these approaches.<br><br>RECENT FINDINGS: The small number of randomized controlled trials (RCTs) using probiotics in CDI have produced variable results; the most recent showed no benefit in preventing disease. However, several meta-analyses published in the last year have suggested benefit in their use, but these conclusions are limited by the poor quality of many of the primary studies, and lack of standardization of the probiotic administered. In contrast, FMT appears highly effective for the treatment of CDI. In the only published RCT, the cure rate was 81%, which is close to the rate shown by meta-analyses of previous case series. The use of artificially produced bacterial mixtures in place of faecal samples is now under investigation.<br><br>SUMMARY: Biological therapies for CDI, especially FMT, will continue to attract attention. Further, large-scale RCTs are required to identify which patients are most likely to benefit from these therapies in the future.}, }
@article {pmid23981941, year = {2013}, author = {Ko, JS}, title = {[The intestinal microbiota and human disease].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {62}, number = {2}, pages = {85-91}, doi = {10.4166/kjg.2013.62.2.85}, pmid = {23981941}, issn = {2233-6869}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/isolation &amp; purification/pathogenicity ; Enterocolitis, Pseudomembranous/drug therapy/microbiology/pathology ; Fatty Liver/etiology/microbiology ; Humans ; Inflammatory Bowel Diseases/etiology/microbiology ; Intestines/*microbiology ; *Microbiota ; Obesity/etiology/microbiology ; }, abstract = {Advances in sequencing technology and the development of metagenomics have opened up new ways to investigate the microorganisms inhabiting the human gut. The intestinal microbiota confer protection against pathogens, contribute to the maturation of the immune system, and regulate host metabolism. The composition of gut microbiota in early life is influenced by mode of birth, diet, and antibiotics. Decreased biodiversity and alterations in the composition of the intestinal microbiota have been observed in many diseases including obesity, neonatal necrotizing enterocolitis, inflammatory bowel disease, and recurrent Clostridium difficile infection. Therapeutic options for the diseases linked to imbalance in the microbiota include modifying the gut microbiota through diet, probiotics, and fecal transplants.}, }
@article {pmid23979974, year = {2013}, author = {Orenstein, R and Griesbach, CL and DiBaise, JK}, title = {Moving fecal microbiota transplantation into the mainstream.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {28}, number = {5}, pages = {589-598}, doi = {10.1177/0884533613497516}, pmid = {23979974}, issn = {1941-2452}, mesh = {Clostridioides difficile ; Clostridium Infections/*therapy ; Feces/*microbiology ; Humans ; *Microbiota ; Probiotics/*administration &amp; dosage ; Recurrence ; Transplantation/*methods ; Treatment Outcome ; United States/epidemiology ; }, abstract = {In recent years, fecal microbiota transplantation (aka fecal transplantation, fecal bacteriotherapy, FMT) has become increasing utilized to treat recurrent and refractory Clostridium difficile infection (CDI). Almost 600,000 cases of CDI occur each year in the United States. Of these, an estimated 15,000 patients have a recurrence. The management of recurrent disease has been challenging for patients and clinicians. Increasingly, FMT has been recognized as an effective option for these patients. This article explores why FMT has reemerged as a practical therapeutic modality. In the process, the logistics by which the procedure is performed and the factors that may affect quality, safety, and patient outcomes will be described.}, }
@article {pmid23969226, year = {2014}, author = {Gollwitzer, ES and Marsland, BJ}, title = {Microbiota abnormalities in inflammatory airway diseases - Potential for therapy.}, journal = {Pharmacology &amp; therapeutics}, volume = {141}, number = {1}, pages = {32-39}, doi = {10.1016/j.pharmthera.2013.08.002}, pmid = {23969226}, issn = {1879-016X}, mesh = {Dysbiosis/complications/*diet therapy ; Humans ; Inflammation/complications/*diet therapy/*microbiology ; Lung Diseases/complications/*diet therapy/*microbiology ; *Prebiotics ; Probiotics/*therapeutic use ; Respiratory System/drug effects/microbiology ; *Synbiotics ; }, abstract = {Increasingly the development of novel therapeutic strategies is taking into consideration the contribution of the intestinal microbiota to health and disease. Dysbiosis of the microbial communities colonizing the human intestinal tract has been described for a variety of chronic diseases, such as inflammatory bowel disease, obesity and asthma. In particular, reduction of several so-called probiotic species including Lactobacilli and Bifidobacteria that are generally considered to be beneficial, as well as an outgrowth of potentially pathogenic bacteria is often reported. Thus a tempting therapeutic approach is to shape the constituents of the microbiota in an attempt to restore the microbial balance towards the growth of 'health-promoting' bacterial species. A twist to this scenario is the recent discovery that the respiratory tract also harbors a microbiota under steady-state conditions. Investigators have shown that the microbial composition of the airway flora is different between healthy lungs and those with chronic lung diseases, such as asthma, chronic obstructive pulmonary disease as well as cystic fibrosis. This is an emerging field, and thus far there is very limited data showing a direct contribution of the airway microbiota to the onset and progression of disease. However, should future studies provide such evidence, the airway microbiota might soon join the intestinal microbiota as a target for therapeutic intervention. In this review, we highlight the major advances that have been made describing the microbiota in chronic lung disease and discuss current and future approaches concerning manipulation of the microbiota for the treatment and prevention of disease.}, }
@article {pmid23967542, year = {2013}, author = {Lofland, D and Josephat, F and Partin, S}, title = {Fecal transplant for recurrent Clostridium difficile infection.}, journal = {Clinical laboratory science : journal of the American Society for Medical Technology}, volume = {26}, number = {3}, pages = {131-135}, pmid = {23967542}, issn = {0894-959X}, mesh = {*Clostridioides difficile ; Colon/microbiology ; Colonoscopy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Female ; Humans ; Middle Aged ; Transplantation/*methods ; Transplants ; }, abstract = {Clostridium difficile infection (CDI) results in clinical manifestations ranging from mild diarrhea to life-threatening pseudomembranous colitis. Infection is most often initiated by antimicrobial therapy which causes an imbalance in normal colonic microflora. The pathogenesis of C. difficile is predominantly controlled by the production of its two cytotoxins, A and B, which damage the intestinal mucosa. In recent years a nationwide increase in the rate of CDI has been noted as well as an increase in mortality, reduced initial response to antimicrobials, extended resolution time, and increased rates of recurrence. Traditional treatment includes administration of antimicrobials. Fecal microbiota transplant (FMT) is an alternative therapy for CDI that is effective and promising in multiple CDI relapse patients. This paper will provide an overview of CDI epidemiology, pathogenesis, diagnosis, and treatment, and explore the case of a 53-year-old woman suffering from her sixth episode of CDI.}, }
@article {pmid23966282, year = {2013}, author = {Gens, KD and Elshaboury, RH and Holt, JS}, title = {Fecal microbiota transplantation and emerging treatments for Clostridium difficile infection.}, journal = {Journal of pharmacy practice}, volume = {26}, number = {5}, pages = {498-505}, doi = {10.1177/0897190013499527}, pmid = {23966282}, issn = {1531-1937}, mesh = {Animals ; Antibodies, Monoclonal/administration &amp; dosage/immunology ; Bacterial Proteins/immunology ; Bacterial Toxins/immunology ; Bacterial Vaccines/administration &amp; dosage/immunology ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/epidemiology/microbiology/*therapy ; Enterotoxins/immunology ; Feces/*microbiology ; Humans ; Incidence ; Secondary Prevention ; }, abstract = {Due to the increased incidence and recurrence of Clostridium difficile infection, health care providers are seeking new and alternative treatments to the standard antibiotic therapy. The objective of this article is to present a review on the background, microbiologic efficacy, clinical efficacy, and safety of fecal microbiota transplantation and to provide an overview of emerging treatment options currently under investigation. Emerging treatment options discussed include the use of monoclonal antibodies directed against toxins A and B, C difficile vaccination, and transplantation of nontoxigenic C difficile strains.}, }
@article {pmid23963839, year = {2014}, author = {Lebas, A and Rogosnitzky, M and Chater, C and Colombel, JF and Nachury, M and Cortot, A and Zerbib, P}, title = {Efficacy of sacral nerve stimulation for poor functional results of J-pouch ileoanal anastomosis.}, journal = {Techniques in coloproctology}, volume = {18}, number = {4}, pages = {355-360}, pmid = {23963839}, issn = {1128-045X}, mesh = {Adult ; Anal Canal/*innervation ; Anastomosis, Surgical ; *Colonic Pouches ; Electric Stimulation Therapy/*methods ; Fecal Incontinence/*therapy ; Female ; Follow-Up Studies ; Humans ; Lumbosacral Plexus/*physiology ; Middle Aged ; Proctocolectomy, Restorative/*methods ; Quality of Life ; Treatment Outcome ; Young Adult ; }, abstract = {PURPOSE: Ileoanal anastomoses (J-pouches) are an alternative to permanent ostomy. The functional outcomes associated with the use of J-pouches are usually good, but continence disorders persist in a significant number of cases and have a negative impact on quality of life. The aim of this study was to assess the efficacy of sacral nerve stimulation (SNS) for poor functional results after J-pouch ileoanal anastomosis.<br><br>METHODS: Patients suffering from severe fecal incontinence (FI) following coloproctectomy underwent a staged implant SNS procedure. Demographic data and functional results for FI episodes, urgencies per week, frequency of stools, ability to defer defecation, and Wexner scores were obtained at specified intervals. Patients also completed quality-of-life assessments.<br><br>RESULTS: Four female patients were included in this analysis. All 4 experienced active and passive FI at baseline and subsequently underwent test stimulation with a 75&#xa0;% success rate. Three received definitive implants. These 3 patients experienced improvement in functional outcomes at 1, 3, and 6&#xa0;month assessments. Improvements in quality of life were also noted.<br><br>CONCLUSIONS: Our preliminary study suggests that SNS is effective for the treatment of poor functional results following J-pouch ileoanal anastomosis; however, larger studies with long-term follow-up are needed for confirmation of our findings.}, }
@article {pmid23951193, year = {2013}, author = {Zanotti, I and Greco, D and Lusardi, G and Zimetti, F and Potì, F and Arnaboldi, L and Corsini, A and Bernini, F}, title = {Cyclosporine A impairs the macrophage reverse cholesterol transport in mice by reducing sterol fecal excretion.}, journal = {PloS one}, volume = {8}, number = {8}, pages = {e71572}, pmid = {23951193}, issn = {1932-6203}, mesh = {ATP-Binding Cassette Transporters/genetics/metabolism ; Animals ; Apolipoproteins E/genetics/metabolism ; Biological Transport/drug effects ; Cholesterol/*metabolism ; Cholesterol 7-alpha-Hydroxylase/antagonists &amp; inhibitors/genetics/*metabolism ; Cyclosporine/*administration &amp; dosage ; Feces/chemistry ; Gene Expression Regulation/drug effects ; Intestinal Mucosa/metabolism ; Intestines/drug effects ; Kinetics ; Liver/drug effects/metabolism ; Macrophages, Peritoneal/cytology/*drug effects/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Sitosterols/blood ; Tritium ; }, abstract = {Despite the efficacy in reducing acute rejection events in organ transplanted subjects, long term therapy with cyclosporine A is associated with increased atherosclerotic cardiovascular morbidity. We studied whether this drug affects the antiatherogenic process of the reverse cholesterol transport from macrophages in vivo. Cyclosporine A 50 mg/kg/d was administered to C57BL/6 mice by subcutaneous injection for 14 days. Macrophage reverse cholesterol transport was assessed by following [(3)H]-cholesterol mobilization from pre-labeled intraperitoneally injected macrophages, expressing or not apolipoprotein E, to plasma, liver and feces. The pharmacological treatment significantly reduced the amount of radioactive sterols in the feces, independently on the expression of apolipoprotein E in the macrophages injected into recipient mice and in absence of changes of plasma levels of high density lipoprotein-cholesterol. Gene expression analysis revealed that cyclosporine A inhibited the hepatic levels of cholesterol 7-alpha-hydroxylase, concomitantly with the increase in hepatic and intestinal expression of ATP Binding Cassette G5. However, the in vivo relevance of the last observation was challenged by the demonstration that mice treated or not with cyclosporine A showed the same levels of circulating beta-sitosterol. These results indicate that treatment of mice with cyclosporine A impaired the macrophage reverse cholesterol transport by reducing fecal sterol excretion, possibly through the inhibition of cholesterol 7-alpha-hydroxylase expression. The current observation may provide a potential mechanism for the high incidence of atherosclerotic coronary artery disease following the immunosuppressant therapy in organ transplanted recipients.}, }
@article {pmid23947094, year = {2013}, author = {McKinney, M}, title = {FDA slaps regs on fecal transplants. Increased steps for C. diff treatment draw mixed reactions from providers.}, journal = {Modern healthcare}, volume = {43}, number = {21}, pages = {10}, pmid = {23947094}, issn = {0160-7480}, mesh = {Biological Products/*standards ; Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Feces/*microbiology ; Humans ; Investigational New Drug Application ; United States ; United States Food and Drug Administration/*standards ; }, }
@article {pmid23945050, year = {2013}, author = {Kononowa, N and Dickenmann, MJ and Kim, MJ}, title = {Severe hyperkalemia following colon diversion surgery in a patient undergoing chronic hemodialysis: a case report.}, journal = {Journal of medical case reports}, volume = {7}, number = {}, pages = {207}, pmid = {23945050}, issn = {1752-1947}, abstract = {INTRODUCTION: Potassium (K+) homeostasis in healthy subjects is maintained mainly by urinary excretion of K+. In patients with end-stage renal disease, the intestinal tract might assume an accessory K+ excretory role in the face of declining renal excretory function. Here, we report the case of a patient with end-stage renal disease who developed severe hyperkalemia following colon diversion surgery.<br><br>CASE PRESENTATION: A 56-year-old Caucasian woman undergoing hemodialysis experienced ischemic colitis, leading to ileocecal resection and a temporary ileostomy. She made a good recovery and her dietary intake improved. However, her pre-dialysis serum K+ level three weeks later was 7.2mmol/L, which was much higher than her previous level (range 4.9 to 6.1mmol/L). Despite dietary restriction of K+ and use of oral cation-exchange resin and low K+ dialysate, her serum K+ level remained high (6.1 to 8.3mmol/L). Six months later, her bowel continuity was restored and her serum K+ decreased to the previous level. Her fecal K+ concentration before and after stoma reversal showed a marked difference: 23mmol/L before and 60mmol/L after.<br><br>CONCLUSIONS: We assume that the severe hyperkalemia seen in our patient was caused by reduced colonic K+ secretion due to the colon diversion. Our patient's case demonstrates the importance of colonic K+ secretion for the maintenance of K+ homeostasis in patients with end-stage renal disease.}, }
@article {pmid23941755, year = {2013}, author = {Price, CE and Cox, S and Rode, H}, title = {The use of diverting colostomies in paediatric peri-anal burns: experience in 45 patients.}, journal = {South African journal of surgery. Suid-Afrikaanse tydskrif vir chirurgie}, volume = {51}, number = {3}, pages = {102-105}, doi = {10.7196/sajs.1398}, pmid = {23941755}, issn = {0038-2361}, mesh = {Adolescent ; Anal Canal/*injuries/microbiology ; Burns/*surgery ; Buttocks/injuries/microbiology ; Child ; Child, Preschool ; *Colostomy/adverse effects ; Graft Survival ; Humans ; Infant ; Infant, Newborn ; Perineum/injuries/microbiology ; Skin Diseases, Bacterial/prevention &amp; control ; Skin Transplantation ; Thigh/injuries/microbiology ; *Wound Healing ; }, abstract = {BACKGROUND: Peri-anal burns are common in children. Continual exposure to enteric organisms may lead to a contaminated burn wound, invasive sepsis, graft loss, scar contracture, anal and urinary malfunction, and delayed discharge from hospital. Use of a temporary diverting colostomy has been advocated to reduce complications.<br><br>OBJECTIVES: To review the incidence, indications, methods, bacteriology, therapeutic effects and outcomes of colostomy for perianal burns.<br><br>METHODS: A prospective study of children with peri-anal burns and stomas over a 17-year period. Prophylactic or therapeutic faecal diversion was achieved by temporary, divided sigmoid end-colostomy with Hartmann's closure of the distal end.<br><br>RESULTS: Between 1995 and 2012, 45 children with peri-anal burns received a colostomy. The mean total body surface area burned was 35% (range 3 - 80%). There were 28 flame burns, 16 fluid burns and 1 contact burn. Prophylactic colostomies were performed in 29 children, on average on day 6 after admission, and therapeutic colostomies to counteract deep wound infection and septicaemia in 16 patients, on average on day 24. In all but 2 cases there was a marked improvement in clinical appearance, graft take and healing. The bacterial profile changed from gut-derived organisms to Pseudomonas aeruginosa or no pathogens. Complications occurred in 5 patients (11.1%). Three stomas required manual reduction. Two children died of established septic shock, compounded by stomal dehiscence in 1 case. Reversal of the colostomy was performed on average at 4 months.<br><br>CONCLUSION: Diverting colostomy has therapeutic advantages in a select group of paediatric burns patients in whom continual faecal soiling poses a threat to both graft and life.}, }
@article {pmid23923106, year = {2013}, author = {Karadsheh, Z and Sule, S}, title = {Fecal transplantation for the treatment of recurrent clostridium difficile infection.}, journal = {North American journal of medical sciences}, volume = {5}, number = {6}, pages = {339-343}, pmid = {23923106}, issn = {2250-1541}, abstract = {Clostridium difficile infection (CDI) is currently a leading cause of antibiotic and health care-related diarrhea. The incidence and the severity of CDI-related diarrhea have increased dramatically in the USA and Europe in the past few decades. The emergence of multidrug-resistant hypervirulent strains of C. difficile has led to an increase in mortality. Fecal microbiota transplantation (FMT) (also known as fecal bacteriotherapy) has been utilized sporadically since the 1950s; and currently, the interest in using FMT has grown again in the past few years for the treatment of CDI and other chronic gastrointestinal diseases. FMT has shown to be effective, cheap, and has very few side effects. It is believed to manipulate and restore the gut microbiota, and therefore enhances the growth of "healthy" bacteria that break the cycle of recurrent CDI. This article focus on the recent case reports on FMT, and general approach to patients undergoing this therapy. Data were obtained through a literature search via PubMed and Google.}, }
@article {pmid23922461, year = {2013}, author = {Vyas, D and L'esperance, HE and Vyas, A}, title = {Stool therapy may become a preferred treatment of recurrent Clostridium difficile?.}, journal = {World journal of gastroenterology}, volume = {19}, number = {29}, pages = {4635-4637}, pmid = {23922461}, issn = {2219-2840}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*pathogenicity ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*therapy ; Feces/*microbiology ; Humans ; Intubation, Gastrointestinal ; Recurrence ; Treatment Outcome ; }, abstract = {Fecal enemas were first reported to successfully treat life threatening enterocolitis in 1958, but fecal therapy to treat Clostridium difficile (C. difficile) infection has remained esoteric and not well investigated until recently. In the past few years, systematic reviews of case series and case reports of fecal microbiota transplant for recurrent C. difficile infection have become available and validate use of fecal transplant for C. difficile enterocolitis. Methods of fecal transplant reported in the literature include: nasogastric tube, gastroscope, duodenal tube, colonoscopy, rectal tube, and fecal enemas administered at home; no method has been shown to be superior. A recent randomized study published in New England Journal of Medicine found fecal transplant to be superior to oral vancomycin alone in treatment of recurrent C. difficile enterocolitis. The significance of this trial cannot be underestimated as it lends credibility to the idea of intentionally using microbes to combat disease, providing an alternative to the older paradigm of disease eradication through use of antimicrobials.}, }
@article {pmid23912409, year = {2013}, author = {Brandt, LJ}, title = {FMT: first step in a long journey.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {8}, pages = {1367-1368}, doi = {10.1038/ajg.2013.165}, pmid = {23912409}, issn = {1572-0241}, mesh = {*Enema ; Enterocolitis/*microbiology/*therapy ; *Feces ; Humans ; Intestines/*microbiology ; *Metagenome ; *Transplantation, Homologous ; }, }
@article {pmid23912408, year = {2013}, author = {Schwartz, M and Gluck, M and Koon, S}, title = {Norovirus gastroenteritis after fecal microbiota transplantation for treatment of Clostridium difficile infection despite asymptomatic donors and lack of sick contacts.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {8}, pages = {1367}, doi = {10.1038/ajg.2013.164}, pmid = {23912408}, issn = {1572-0241}, mesh = {*Enema ; Enterocolitis/*microbiology/*therapy ; *Feces ; Humans ; Intestines/*microbiology ; *Metagenome ; *Transplantation, Homologous ; }, }
@article {pmid23910407, year = {2013}, author = {Patel, NC and Griesbach, CL and DiBaise, JK and Orenstein, R}, title = {Fecal microbiota transplant for recurrent Clostridium difficile infection: Mayo Clinic in Arizona experience.}, journal = {Mayo Clinic proceedings}, volume = {88}, number = {8}, pages = {799-805}, doi = {10.1016/j.mayocp.2013.04.022}, pmid = {23910407}, issn = {1942-5546}, mesh = {Abdominal Pain/physiopathology ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*pathogenicity ; Colonoscopy/methods ; Diarrhea/physiopathology ; Drug Resistance, Multiple, Bacterial ; *Enterocolitis, Pseudomembranous/microbiology/physiopathology/therapy ; Feces/*microbiology ; Female ; Humans ; Intestines/microbiology ; Male ; *Microbiota ; Middle Aged ; Recurrence ; Retrospective Studies ; Transplantation/*methods ; Treatment Outcome ; }, abstract = {OBJECTIVE: To report the initial experience of treating recurrent Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) at Mayo Clinic in Arizona.<br><br>PATIENTS AND METHODS: The study retrospectively reviewed FMTs performed at Mayo Clinic in Arizona between January 1, 2011, and January 31, 2013. All the recipients had multiple recurrent CDIs unresponsive to traditional antibiotic drug therapy. A standardized protocol was developed to identify patients, screen donors, perform FMT, and determine outcomes via telephone surveys.<br><br>RESULTS: Thirty-one patients (mean &#xb1; SD age, 61.26&#xb1;19.34 years) underwent FMT. Median time from index infection to FMT was 340 days. Ninety-seven percent (29 of 30) of patients reported substantial improvement or resolution of diarrhea (median time to improvement, 3 days), 74% (17 of 23) reported improvement or resolution of abdominal pain (median time to improvement, 3 days), and 55% (16 of 29) had improvement or resolution of fatigue (median time to improvement, 6 days). Three patients underwent repeated FMT owing to persistent symptoms; 2 reported improvement in diarrhea with the second therapy. No serious adverse events directly related to FMT were reported.<br><br>CONCLUSION: A standardized regimen of FMT for recurrent CDI is safe, is highly effective, and can be provided using a relatively simple protocol.}, }
@article {pmid23910405, year = {2013}, author = {Baron, TH and Kozarek, RA}, title = {Fecal microbiota transplant: we know its history, but can we predict its future?.}, journal = {Mayo Clinic proceedings}, volume = {88}, number = {8}, pages = {782-785}, doi = {10.1016/j.mayocp.2013.06.007}, pmid = {23910405}, issn = {1942-5546}, mesh = {Clostridioides difficile/*pathogenicity ; *Enterocolitis, Pseudomembranous ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; Transplantation/*methods ; }, }
@article {pmid23910373, year = {2013}, author = {Dinan, TG and Cryan, JF}, title = {Melancholic microbes: a link between gut microbiota and depression?.}, journal = {Neurogastroenterology and motility}, volume = {25}, number = {9}, pages = {713-719}, doi = {10.1111/nmo.12198}, pmid = {23910373}, issn = {1365-2982}, mesh = {Animals ; Depression/*microbiology/physiopathology ; Gastrointestinal Tract/*microbiology/physiopathology ; Humans ; Hypothalamo-Hypophyseal System/physiopathology ; Microbiota ; Pituitary-Adrenal System/physiopathology ; }, abstract = {There is a growing awareness of the potential for microbiota to influence gut-brain communication in health and disease. A variety of strategies have been used to study the impact of the microbiota on brain function and these include antibiotic use, probiotic treatments, fecal microbiota transplantation, gastrointestinal infection studies, and germ-free studies. All of these approaches provide evidence to support the view that the microbiota can influence brain chemistry and consequently behavior. Efforts are now turning to investigate the role of microbiota in animal models of psychopathology. Animal models of depression are thus essential in studying the complex interplay between the microbiota and brain. Recent studies published in this Journal and elsewhere demonstrate that there is a distinct perturbation of the composition of gut microbiota in animal models of depression and chronic stress. This has direct implications for the development of psychobiotic-based therapeutic strategies for psychiatric disorders. Moreover, given that affective co-morbidities, such as major depression and anxiety states, are common in patients presenting with irritable bowel syndrome (IBS), it may have implications for functional bowel disorders also. Further studies require appropriately phenotyped patients with depression and/or IBS using a judicious use of techniques including functional imaging and in depth microbial pyrosequencing.}, }
@article {pmid23899544, year = {2013}, author = {Kump, PK and Gröchenig, HP and Lackner, S and Trajanoski, S and Reicht, G and Hoffmann, KM and Deutschmann, A and Wenzl, HH and Petritsch, W and Krejs, GJ and Gorkiewicz, G and Högenauer, C}, title = {Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis.}, journal = {Inflammatory bowel diseases}, volume = {19}, number = {10}, pages = {2155-2165}, doi = {10.1097/MIB.0b013e31829ea325}, pmid = {23899544}, issn = {1536-4844}, mesh = {Adolescent ; Adult ; *Biological Therapy ; Chronic Disease ; Clostridium Infections/genetics/microbiology/*therapy ; Colitis, Ulcerative/genetics/microbiology/*therapy ; Dysbiosis/genetics/microbiology/*prevention &amp; control ; Feces/*microbiology ; Female ; Follow-Up Studies ; Humans ; Intestines/microbiology ; Male ; Metagenome/*genetics ; *Microbiota ; Middle Aged ; Phylogeny ; Prognosis ; RNA, Ribosomal, 16S/analysis ; Remission Induction ; Transplantation ; }, abstract = {BACKGROUND: In patients with ulcerative colitis (UC), alterations of the intestinal microbiota, termed dysbiosis, have been postulated to contribute to intestinal inflammation. Fecal microbiota transplantation (FMT) has been used as effective therapy for recurrent Clostridium difficile colitis also caused by dysbiosis. The aims of the present study were to investigate if patients with UC benefit from FMT and if dysbiosis can be reversed.<br><br>METHODS: Six patients with chronic active UC nonresponsive to standard medical therapy were treated with FMT by colonoscopic administration. Changes in the colonic microbiota were assessed by 16S rDNA-based microbial community profiling using high-throughput pyrosequencing from mucosal and stool samples.<br><br>RESULTS: All patients experienced short-term clinical improvement within the first 2 weeks after FMT. However, none of the patients achieved clinical remission. Microbiota profiling showed differences in the modification of the intestinal microbiota between individual patients after FMT. In 3 patients, the colonic microbiota changed toward the donor microbiota; however, this did not correlate with clinical response. On phylum level, there was a significant reduction of Proteobacteria and an increase in Bacteroidetes after FMT.<br><br>CONCLUSIONS: FMT by a single colonoscopic donor stool application is not effective in inducing remission in chronic active therapy-refractory UC. Changes in the composition of the intestinal microbiota were significant and resulted in a partial improvement of UC-associated dysbiosis. The results suggest that dysbiosis in UC is at least in part a secondary phenomenon induced by inflammation and diarrhea rather than being causative for inflammation in this disease.}, }
@article {pmid23897227, year = {2013}, author = {Muthiah, K and Robson, D and Macdonald, PS and Keogh, AM and Kotlyar, E and Granger, E and Dhital, K and Spratt, P and Hayward, CS}, title = {Increased incidence of angiodysplasia of the gastrointestinal tract and bleeding in patients with continuous flow left ventricular assist devices (LVADs).}, journal = {The International journal of artificial organs}, volume = {36}, number = {7}, pages = {449-454}, doi = {10.5301/ijao.5000224}, pmid = {23897227}, issn = {1724-6040}, mesh = {Adult ; Aged ; Angiodysplasia/diagnosis/*epidemiology ; Endoscopy, Gastrointestinal ; Female ; Gastrointestinal Hemorrhage/diagnosis/*epidemiology ; Heart Failure/diagnosis/epidemiology/physiopathology/*therapy ; Heart-Assist Devices/*adverse effects ; Humans ; Incidence ; Male ; Middle Aged ; New South Wales/epidemiology ; Occult Blood ; Prosthesis Design ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; *Ventricular Function, Left ; }, abstract = {BACKGROUND: Continuous flow left ventricular assist devices (cfLVADs) are used in clinical practice for the management of end-stage heart failure. Axial flow cfLVADS have been associated with increased rates of adverse gastrointestinal events such as bleeding angiodysplasia. The purpose of this study was to determine the incidence of bleeding gastrointestinal tract angiodysplasia and the profile of patients supported with the centrifugal cfLVAD, referred for endoscopy.<br><br>METHODS: A retrospective analysis of 66 patients implanted with Ventrassist (n = 33) and Heartware (n = 33) centrifugal continuous flow LVADs was performed. All patients were on warfarin, aspirin and/or clopidogrel. Endoscopy was performed in all patients with either active gastrointestinal bleeding (n = 6) or anemia with positive fecal occult blood (n = 6).<br><br>RESULTS: Bleeding gastrointestinal angiodysplasia was demonstrated in 5 out of the 12 (41.6%) patients who underwent endoscopy from the cohort of 66 cfLVAD supported patients (7.6%). The incidence of bleeding angiodysplasia was higher than the age-standardized rate of andiodysplasia from literature (0.8%). Active gastrointestinal bleeding in one other patient was due to diverticulosis. The five patients with bleeding angiodysplasia tended to be older than the remaining 61 patients (58.8 &#xb1; 10.3 vs 49.6 &#xb1; 15.7 years, p = 0.2).<br><br>CONCLUSIONS: We found excess bleeding angiodysplasia in patients on centrifugal cfLVAD support. It may be appropriate to screen for angiodysplasia particularly in older patients prior to support by centrifugal cf LVADs. Reasons for the higher rate of bleeding angiodysplasia in cfLVAD patients warrant further study.}, }
@article {pmid23870000, year = {2013}, author = {, }, title = {ALS Untangled No. 21: Fecal transplants.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {14}, number = {5-6}, pages = {482-485}, doi = {10.3109/21678421.2013.814981}, pmid = {23870000}, issn = {2167-9223}, mesh = {Amyotrophic Lateral Sclerosis/*therapy ; Animals ; Biological Therapy/methods ; Feces/*microbiology ; Humans ; *Metagenome ; *Transplantation ; }, }
@article {pmid23869970, year = {2013}, author = {Burke, KE and Lamont, JT}, title = {Fecal transplantation for recurrent Clostridium difficile infection in older adults: a review.}, journal = {Journal of the American Geriatrics Society}, volume = {61}, number = {8}, pages = {1394-1398}, doi = {10.1111/jgs.12378}, pmid = {23869970}, issn = {1532-5415}, mesh = {Aged ; Aged, 80 and over ; *Clostridioides difficile/genetics/pathogenicity ; Enterocolitis, Necrotizing/microbiology/*therapy ; Feces/*microbiology ; Female ; Follow-Up Studies ; Genotype ; Humans ; Male ; *Metagenome ; Middle Aged ; Randomized Controlled Trials as Topic ; Recurrence ; *Transplants ; Treatment Failure ; Virulence/genetics ; }, abstract = {Recurrent Clostridium difficile infection (CDI) is a common nosocomial infection that has a large effect on morbidity and quality of life in older adults in hospitals and long-term care facilities. Because antibiotics are often unsuccessful in curing this disease, fecal transplantation has emerged as a second-line therapy for treatment of recurrent CDI. A comprehensive literature search of PubMed, Embase, and Web of Science regarding fecal transplantation for CDI was performed to further evaluate the efficacy and side effects of this promising therapy in older adults. Data were extracted from 10 published articles from 1984 to the present that met inclusion criteria, including nine open-label reports and one randomized controlled trial. Baseline characteristics and outcomes of individuals undergoing fecal transplantation and effects of fecal transplantation on the fecal microflora were reviewed. Methods of fecal transplantation and donor selection were reviewed. Fecal transplantation was performed in 115 individuals aged 60 to 101, with a female predominance. CDI cure was achieved in 103 (89.6%) individuals over a follow-up period of 2 months to 5 years (mean 5.9 months). There was no significant difference in cure rate between older and younger participants in included studies. Most failed transplantation occurred in individuals infected with the aggressive NAP1/027 strain of C. difficile. Microbiological studies of fecal biodiversity before and after fecal transplantation demonstrated greater bacterial diversity and shift in flora species to resemble donor flora after transplantation that correlated with clinical remission. Fecal transplantation provides a safe and durable cure for older adults with recurrent CDI.}, }
@article {pmid23867679, year = {2013}, author = {Marathe, A and Parikh, K}, title = {Severe diarrhoea due to Cystoisospora belli in renal transplant patient on immunosuppressive drugs.}, journal = {Indian journal of medical microbiology}, volume = {31}, number = {2}, pages = {185-187}, doi = {10.4103/0255-0857.115227}, pmid = {23867679}, issn = {1998-3646}, mesh = {Antiprotozoal Agents/therapeutic use ; Coccidiosis/*diagnosis/parasitology/pathology ; Diarrhea/*parasitology/pathology ; Feces/parasitology ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/administration &amp; dosage/*adverse effects ; India ; Kidney Transplantation ; Male ; Microscopy ; Middle Aged ; Nitro Compounds ; Sarcocystidae/*isolation &amp; purification ; Thiazoles/therapeutic use ; Transplantation ; Treatment Outcome ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use ; }, abstract = {Cystoisospora belli, formerly known as Isospora belli, protozoal parasite endemic to many regions of the world including the Caribbean, Central and South America, Africa, and South-East Asia. It is frequently encountered in patients with acquired immunodeficiency syndrome (AIDS) and is considered to be an AIDS-defining illness. Chronic severe watery diarrhoea due to C. belli has also been reported in other immunodeficiency states. C. belli infection in immunosuppressed patients has rarely been described. We describe severe diarrhoea due to C. belli in a human immunodeficiency virus-negative renal transplant recipient on immunosuppressive drugs. Oocysts of C. belli were detected in direct smear preparation of the diarrheic stool sample of the patient. The patient responded to combination treatment with Bactrim-double-strength (trimethoprim-sulfamethoxazole) and Nitazoxanide.}, }
@article {pmid23866975, year = {2013}, author = {Adamu, BO and Lawley, TD}, title = {Bacteriotherapy for the treatment of intestinal dysbiosis caused by Clostridium difficile infection.}, journal = {Current opinion in microbiology}, volume = {16}, number = {5}, pages = {596-601}, pmid = {23866975}, issn = {1879-0364}, support = {/WT_/Wellcome Trust/United Kingdom ; 098051/WT_/Wellcome Trust/United Kingdom ; 93614/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biological Therapy/adverse effects/*methods ; Clostridioides difficile/*growth &amp; development ; Clostridium Infections/*therapy ; Dysbiosis/*therapy ; Enteritis/*therapy ; Humans ; }, abstract = {Faecal microbiota transplantation (FMT) has been used for more than five decades to treat a variety of intestinal diseases associated with pathological imbalances within the resident microbiota, termed dysbiosis. FMT has been particularly effective for treating patients with recurrent Clostridium difficile infection who are left with few clinical options other than continued antibiotic therapy. Our increasing knowledge of the structure and function of the human intestinal microbiota and C. difficile pathogenesis has led to the understanding that FMT promotes intestinal ecological restoration and highlights the microbiota as a viable therapeutic target. However, the use of undefined faecal samples creates a barrier for widespread clinical use because of safety and aesthetic issues. An emerging concept of bacteriotherapy, the therapeutic use of a defined mixture of harmless, health-associated bacteria, holds promise for the treatment of patients with severe C. difficile infection, and possibly represents a paradigm shift for the treatment of diseases linked to intestinal dysbiosis.}, }
@article {pmid23852569, year = {2013}, author = {Borody, TJ and Paramsothy, S and Agrawal, G}, title = {Fecal microbiota transplantation: indications, methods, evidence, and future directions.}, journal = {Current gastroenterology reports}, volume = {15}, number = {8}, pages = {337}, pmid = {23852569}, issn = {1534-312X}, mesh = {Biological Therapy/*methods/trends ; Enterocolitis, Pseudomembranous/*therapy ; Evidence-Based Medicine/methods ; Feces/*microbiology ; Gastrointestinal Tract/microbiology ; Humans ; Inflammatory Bowel Diseases/*therapy ; Irritable Bowel Syndrome/therapy ; Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) has attracted great interest in recent years, largely due to the global Clostridium difficile infection (CDI) epidemic and major advances in metagenomic sequencing of the gastrointestinal (GI) microbiota, with growing understanding of its structure and function. FMT is now recommended as the most effective therapy for relapsing CDI and, with further refinement, may even be used in "first-time" CDI. There is interest also in other conditions related to GI dysbiosis--for example, inflammatory bowel disease, irritable bowel syndrome, obesity, and diabetes mellitus--although quality evidence is at present lacking. A few trials are now underway in FMT for ulcerative colitis. Many unanswered questions remain, including FMT methodology--for example, optimal route of administration, what makes a "good donor," safety issues, and long-term effects of FMT.}, }
@article {pmid23846489, year = {2013}, author = {Dasgupta, S and Kasper, DL}, title = {Relevance of commensal microbiota in the treatment and prevention of inflammatory bowel disease.}, journal = {Inflammatory bowel diseases}, volume = {19}, number = {11}, pages = {2478-2489}, doi = {10.1097/MIB.0b013e318297d884}, pmid = {23846489}, issn = {1536-4844}, mesh = {Animals ; Bacteria/growth &amp; development/*immunology ; Humans ; Inflammatory Bowel Diseases/immunology/*microbiology/*prevention &amp; control ; Microbiota/*immunology ; }, abstract = {Commensal microbiota that reside primarily in the gut of mammals influence the hosts' health to a great extent. Shaping of host immunity locally, a vital component of this influence, can have pro-inflammatory, anti-inflammatory, or neutral outcomes, presumably depending on the composition of the microbiota in an individual and type of molecules expressed in the individual members of the microbiota. Thus, these microbial species can be thought of as a reservoir of molecules that can be used to improve or worsen the condition of patients suffering from immunity or inflammation-driven pathologies like inflammatory bowel disease. In the current review, we elaborate, based on the literature available from murine models of disease and clinical case studies, the need to identify individual members of commensal microbiota that can precipitate or resolve inflammatory bowel disease. Therapeutic approaches could entail enrichment of members of microbiota (or molecules from these microbes), which induces expansion or enhancement of function of regulatory T cells or tolerogenic dendritic cells and reduce members that cause inflammation either directly or indirectly by influencing metabolic and other host molecules. Efficiency of bacteria-driven therapy would potentially be enhanced as we refine our approaches from the use of complete feces as done in fecal transplantation to utilization of microbiota-derived molecules as exemplified by the capsular polysaccharide A from the human gut commensal Bacteroides fragilis. We also highlight the advantages and disadvantages of each approach, defining a natural alternative to the current chemical-based immunosuppressive regimen for patients with inflammatory bowel disease.}, }
@article {pmid23845749, year = {2013}, author = {Collins, SM and Kassam, Z and Bercik, P}, title = {The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications.}, journal = {Current opinion in microbiology}, volume = {16}, number = {3}, pages = {240-245}, doi = {10.1016/j.mib.2013.06.004}, pmid = {23845749}, issn = {1879-0364}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Biological Therapy/*methods ; Brain/*physiology ; Central Nervous System Diseases/therapy ; Clostridium Infections/therapy ; Diabetes Mellitus/therapy ; Gastrointestinal Tract/*microbiology ; Inflammatory Bowel Diseases/therapy ; Mice ; *Microbiota ; }, abstract = {There is growing interest in the ability of the intestinal microbiome to influence host function within and beyond the gastrointestinal tract. Here we review evidence of microbiome-brain interactions in mice and focus on the ability to transfer behavioral traits between mouse strains using fecal microbiota transplantation (FMT). Transplantation alters brain chemistry and behavior in recipient ex-germ free mice, raising the possibility of using FMT for disorders of the central nervous system, and prompting caution in the selection of FMT donors for conditions that may include refractory Clostridium difficile infection, diabetes and inflammatory bowel disease in humans.}, }
@article {pmid23844515, year = {2013}, author = {Israeli, E and Shoenfeld, Y}, title = {[Harnessing nature for treating infectious and autoimmune diseases: good and bad bacteria].}, journal = {Harefuah}, volume = {152}, number = {4}, pages = {188-9, 249}, pmid = {23844515}, issn = {0017-7768}, mesh = {Anti-Bacterial Agents/administration &amp; dosage/*adverse effects ; Clostridioides difficile/isolation &amp; purification/pathogenicity ; *Enterocolitis/etiology/therapy ; Enterocolitis, Pseudomembranous/*microbiology ; *Gastrointestinal Contents/drug effects/microbiology ; Humans ; Lactobacillus/drug effects/physiology ; Probiotics/*therapeutic use ; }, abstract = {Clostridium difficile is the etiologic agent of nosocomial and community-acquired diarrhea associated with exposure to antibiotics that disrupt the normal colonic flora. As antibacterials currently used for primary C. difficile infections favor recurrences, new methods able to neutralize the bacterium without affecting the gut microbiota are badly needed. Complementary treatment with probiotic agents to reconstitute the physiologicaL intestinal flora does not yield any consistent benefit. In recent years, fecal transplantation has been used in the English-speaking countries with cure rates of about 87%. Fecal microbiota transplantation (FMT) holds considerable promise as a therapy for recurrent Clostridium difficile infection, but well-designed, randomized-controlled trials and Long-term follow-up registries are stilt required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated. Another aspect of bad/good parasites are the use of helminth or helminth ova for treating autoimmune diseases, especially those affecting the gut.}, }
@article {pmid23841136, year = {2013}, author = {}, title = {Fecal microbiota transplantation for treating recurrent Clostridium difficile infection.}, journal = {Managed care (Langhorne, Pa.)}, volume = {22}, number = {6}, pages = {18-19}, pmid = {23841136}, issn = {1062-3388}, mesh = {Biological Therapy/methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; Evidence-Based Medicine ; *Feces/microbiology ; Humans ; Intestines/*microbiology ; *Metagenome ; }, }
@article {pmid23839135, year = {2013}, author = {Fox, JL}, title = {Fecal transplants to follow FDA rules.}, journal = {Nature biotechnology}, volume = {31}, number = {7}, pages = {583}, doi = {10.1038/nbt0713-583}, pmid = {23839135}, issn = {1546-1696}, mesh = {Feces/*microbiology ; Humans ; Microbiota ; United States ; United States Food and Drug Administration/*legislation &amp; jurisprudence ; }, }
@article {pmid23839064, year = {2014}, author = {Bonnegarde-Bernard, A and Jee, J and Fial, MJ and Aeffner, F and Cormet-Boyaka, E and Davis, IC and Lin, M and Tomé, D and Karin, M and Sun, Y and Boyaka, PN}, title = {IKKβ in intestinal epithelial cells regulates allergen-specific IgA and allergic inflammation at distant mucosal sites.}, journal = {Mucosal immunology}, volume = {7}, number = {2}, pages = {257-267}, pmid = {23839064}, issn = {1935-3456}, support = {R01 AI043197/AI/NIAID NIH HHS/United States ; }, mesh = {Adjuvants, Immunologic ; Allergens/administration &amp; dosage/*immunology ; Animals ; Antibody Specificity/immunology ; CD4-Positive T-Lymphocytes/immunology/metabolism ; Cholera Toxin/immunology ; Dysbiosis/immunology ; Gene Deletion ; I-kappa B Kinase/genetics/*metabolism ; Immunity, Innate/genetics/immunology ; Immunization ; Immunoglobulin A/*immunology ; Inflammation/*immunology/*metabolism ; Interleukin-17/biosynthesis ; Intestinal Mucosa/*immunology/*metabolism/pathology ; Mice ; Respiratory System/immunology/metabolism/pathology ; Signal Transduction ; }, abstract = {Regulation of allergic responses by intestinal epithelial cells (IECs) remains poorly understood. Using a model of oral allergen sensitization in the presence of cholera toxin as adjuvant and mice with cell-specific deletion of inhibitor-κB kinase (IKKβ) in IECs (IKKβ(ΔIEC)), we addressed the contribution of IECs to allergic sensitization to ingested antigens and allergic manifestations at distant mucosal site of the airways. Cholera toxin induced higher pro-inflammatory responses and altered the profile of the gut microbiota in IKKβ(ΔIEC) mice. Antigen-specific immunoglobulin E (IgE) responses were unaltered in IKKβ(ΔIEC) mice, but their IgA antibodies (Abs), T helper type 1 (Th1) and Th17 responses were enhanced. Upon nasal antigen challenge, these mice developed lower levels of allergic lung inflammation, which correlated with higher levels of IgA Abs in the airways. The IKKβ(ΔIEC) mice also recruited a higher number of gut-sensitized T cells in the airways after nasal antigen challenge and developed airway hyper-responsiveness, which were suppressed by treatment with anti-interleukin-17A. Fecal microbiota transplant during allergic sensitization reduced Th17 responses in IKKβ(ΔIEC) mice, but did not affect IgA Ab responses. In summary, we show that IKKβ in IECs shapes the gut microbiota and immune responses to ingested antigens and influences allergic responses in the airways via regulation of IgA Ab responses.}, }
@article {pmid23838941, year = {2013}, author = {Quigley, EM and Monsour, HP}, title = {Targeting the microbiota in the management of gastrointestinal and liver disease.}, journal = {Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru}, volume = {33}, number = {2}, pages = {139-144}, pmid = {23838941}, issn = {1609-722X}, mesh = {Gastrointestinal Diseases/*microbiology/*therapy ; Humans ; Liver Diseases/*microbiology/*therapy ; *Microbiota ; }, abstract = {Thanks to rapid advances in technology the details of the human microbiome and its functions in health and disease are being progressively revealed. Though many reports have linked various disease states with an altered microbiome and while some associations between the microbiome and disease states are well established, many of these studies are largely descriptive and the changes reported in the microbiome have yet to be shown to be causative. A number of strategies are available to modify the microbiota; some such as the use of antibiotics for specific indications, are well established, others such as the use of probiotics and prebiotics in a variety of disease states are supported by more limited data. Fecal transplantation has emerged as an exciting, albeit rather drastic, intervention for intestinal and, perhaps, other disorders. Other approaches, such as the isolation, purification and formulation of small molecules with specific biological actions, derived from the microbiota look very promising.}, }
@article {pmid23836382, year = {2013}, author = {Chen, YC and Chi, CC and Chan, FC and Wen, YW}, title = {Low molecular weight heparin for prevention of microvascular occlusion in digital replantation.}, journal = {The Cochrane database of systematic reviews}, volume = {}, number = {7}, pages = {CD009894}, doi = {10.1002/14651858.CD009894.pub2}, pmid = {23836382}, issn = {1469-493X}, support = {CZB/4/788/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Anticoagulants/adverse effects/*therapeutic use ; Blood Coagulation Disorders/chemically induced ; Fingers/blood supply/*transplantation ; Heparin/therapeutic use ; Heparin, Low-Molecular-Weight/adverse effects/*therapeutic use ; Humans ; Microvessels/*surgery ; Peripheral Arterial Disease/epidemiology ; Postoperative Hemorrhage/chemically induced ; Randomized Controlled Trials as Topic ; Replantation/*adverse effects ; Venous Insufficiency/epidemiology ; }, abstract = {BACKGROUND: The success of digital replantation is highly dependent on the patency of the repaired vessels after microvascular anastomosis. Antithrombotic agents are frequently used for preventing vascular occlusion. Low molecular weight heparin (LMWH) has been reported to be as effective as unfractionated heparin (UFH) in peripheral vascular surgery, but with fewer adverse effects. Its benefit in microvascular surgery such as digital replantation is unclear.<br><br>OBJECTIVES: To assess whether subcutaneous LMWH treatment improves the salvage rate of the digits in patients with digital replantation after traumatic amputation.<br><br>SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (October 2012), CENTRAL (2012, Issue 10) and trials databases. In addition, the authors searched PubMed, CNKI (China National Knowledge Infrastructure) and CEPS (Chinese Electronic Periodical Services), and sought additional trials from reference lists of relevant publications.<br><br>SELECTION CRITERIA: We selected randomised or quasi-randomised controlled trials of LMWH in patients who received digital replantation.<br><br>DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of the included trials. Disagreements were resolved by discussion.<br><br>MAIN RESULTS: Two randomised trials involving 114 patients with at least 122 replanted digits met the inclusion criteria and were included. Both trials compared the efficacy and safety of LMWH with UFH. We found no trials comparing LMWH with placebo or other anticoagulants. The data from the two included studies were insufficient for meta-analysis. The overall success rate of replantation did not differ between the LMWH and UFH groups, 92.3% versus 89.2% in one trial (risk ratio (RR) 1.03; 95% confidence interval (CI) 0.87 to 1.22) and 94.3% versus 94.15% in the other trial (RR 1.00; 95% CI 0.89 to 1.13). The incidence of both postoperative arterial and venous insufficiency were reported in one trial and did not significantly differ between the LMWH and UFH groups (RR 1.08; 95% CI 0.16 to 7.10 and RR 0.81; 95% CI 0.20 to 3.27, respectively). Direct and indirect causes of microvascular insufficiency were not reported in the trials. Different methods were used to monitor the adverse effects related to anticoagulation in the two trials. Bleeding tendency was monitored for the LMWH and UFH groups in one trial and was reported by the incidence of wound haemorrhage (11.5% versus 17.9%; RR 0.65; 95% CI 0.17 to 2.44), ecchymoses (3.8% versus 10.7%; RR 0.36; 95% CI 0.04 to 3.24), haematuria (3.8% versus 7.1%; RR 0.54; 95% CI 0.05 to 5.59), nasal bleeding (0% versus 7.1%; RR 0.21; 95% CI 0.01 to 4.28), gingival bleeding (0% versus 10.7%; RR 0.15, 95% CI 0.01 to 2.83) and faecal occult blood (0% versus 3.6%; RR 0.36; 95% CI 0.02 to 8.42). The bleeding tendency was increased in the UFH group but this was not statistically significant. This trial also monitored coagulability changes using parameters such as antithrombin activity, factor Xa activity, bleeding time, clotting time and activated partial thromboplastin time (aPTT). No comparison was made between the LMWH and UFH groups but all data consistently showed that coagulability was reduced more in the UFH group than in the LMWH group. The other trial reported a postoperative decrease in platelet count in the UFH group (preoperative 278.4 &#xb1; 18.7 x 10(9)/L, postoperative 194.3 &#xb1; 26.5 x 10(9)/L; P < 0.05) but not in the LMWH group (preoperative 260.8 &#xb1; 32.5 x 10(9)/L, postoperative 252.4 &#xb1; 29.1 x 10(9)/L; P > 0.05).<br><br>AUTHORS' CONCLUSIONS: Current limited evidence based on two small-scaled low-to-medium quality randomised trials found no differences in the success rate of replantation between LMWH and UFH, but a lower risk of postoperative bleeding and hypocoagulability after the use of LMWH. Further well-designed and adequately powered clinical trials are warranted.}, }
@article {pmid23810330, year = {2013}, author = {Kneist, W and Kauff, DW and Juhre, V and Hoffmann, KP and Lang, H}, title = {Is intraoperative neuromonitoring associated with better functional outcome in patients undergoing open TME? Results of a case-control study.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {39}, number = {9}, pages = {994-999}, doi = {10.1016/j.ejso.2013.06.004}, pmid = {23810330}, issn = {1532-2157}, mesh = {Aged ; Aged, 80 and over ; Anal Canal/*innervation ; *Autonomic Pathways ; Case-Control Studies ; Cohort Studies ; Fecal Incontinence/prevention &amp; control ; Female ; Humans ; Lower Urinary Tract Symptoms/prevention &amp; control ; Male ; Middle Aged ; Monitoring, Intraoperative ; Organ Sparing Treatments ; Peripheral Nerve Injuries/*prevention &amp; control ; Prospective Studies ; Rectal Neoplasms/*surgery ; Rectum/*surgery ; Sexual Dysfunction, Physiological/prevention &amp; control ; Treatment Outcome ; Urinary Bladder/*innervation ; }, abstract = {AIMS: Intraoperative neuromonitoring (IONM) aims to control nerve-sparing total mesorectal excision (TME) for rectal cancer in order to improve patients' functional outcome. This study was designed to compare the urogenital and anorectal functional outcome of TME with and without IONM of innervation to the bladder and the internal anal sphincter.<br><br>METHODS: A consecutive series of 150 patients with primary rectal cancer were analysed. Fifteen match pairs with open TME and combined urogenital and anorectal functional assessment at follow up were established identical regarding gender, tumour site, tumour stage, neoadjuvant radiotherapy and type of surgery. Urogenital and anorectal function was evaluated prospectively on the basis of self-administered standardized questionnaires, measurement of residual urine volume and longterm-catheterization rate.<br><br>RESULTS: Newly developed urinary dysfunction after surgery was reported by 1 of 15 patients in the IONM group and by 6 of 15 in the control group (p&#xa0;=&#xa0;0.031). Postoperative residual urine volume was significantly higher in the control group. At follow up impaired anorectal function was present in 1 of 15 patients undergoing TME with IONM and in 6 of 15 without IONM (p&#xa0;=&#xa0;0.031). The IONM group showed a trend towards a lower rate of sexual dysfunction after surgery.<br><br>CONCLUSIONS: In this study TME with IONM was associated with significant lower rates of urinary and anorectal dysfunction. Prospective randomized trials are mandatory to evaluate the definite role of IONM in rectal cancer surgery.}, }
@article {pmid23809712, year = {2013}, author = {Knight, CL and Surawicz, CM}, title = {Clostridium difficile Infection.}, journal = {The Medical clinics of North America}, volume = {97}, number = {4}, pages = {523-36, ix}, doi = {10.1016/j.mcna.2013.02.003}, pmid = {23809712}, issn = {1557-9859}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Antidiarrheals/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/drug therapy/etiology/prevention &amp; control ; Cross Infection/prevention &amp; control ; Humans ; Probiotics/therapeutic use ; Recurrence ; Risk Factors ; Severity of Illness Index ; }, abstract = {Clostridium difficile is emerging as a common cause of infectious diarrhea. Incidence has increased dramatically since 2000, associated with a new strain that features both increased toxin production and increased resistance to antibiotics. For patients with mild to moderate disease, oral metronidazole is usually the first choice of treatment, and those with severe disease should be treated with vancomycin, with additional intravenous metronidazole in some cases. Fecal microbiota transplantation is a potentially promising therapy for patients with multiple recurrences of C difficile infection. Prevention of nosocomial transmission is crucial to reducing disease outbreaks in health care settings.}, }
@article {pmid23778641, year = {2013}, author = {Secher, T and Normand, S and Chamaillard, M}, title = {NOD2 prevents emergence of disease-predisposing microbiota.}, journal = {Gut microbes}, volume = {4}, number = {4}, pages = {353-356}, pmid = {23778641}, issn = {1949-0984}, mesh = {Animals ; Colitis/*etiology ; Colorectal Neoplasms/*etiology ; Female ; Humans ; Male ; Nod2 Signaling Adaptor Protein/*deficiency ; Pregnancy ; }, abstract = {The gut flora is composed of a huge number of diverse, well-adapted symbionts that interact with epithelial lining throughout the host's entire life. Not all commensals have the same ability to maintain quiescent, protective inflammation. Importantly, instability in the composition of gut microbial communities (referred to as dysbiosis) has been linked to loss of gut barrier in the context of common human illnesses with increasing socio-economic impacts, such as Crohn disease and colorectal cancer. Our recent findings suggest that disease-predisposing dysbiosis can now be intentionally manipulated by targeting the major Crohn disease-predisposing NOD2 gene. That knowledge will not only add a new dimension to the often overlooked microbiology of Crohn disease and colorectal cancer, but will also have a broad impact on biomedical sciences worldwide.}, }
@article {pmid23772577, year = {2013}, author = {Bednarska, M and Bajer, A and Welc-Faleciak, R and Czubkowski, P and Teisseyre, M and Graczyk, TK and Jankowska, I}, title = {The first case of Enterocytozoon bieneusi infection in Poland.}, journal = {Annals of agricultural and environmental medicine : AAEM}, volume = {20}, number = {2}, pages = {287-288}, pmid = {23772577}, issn = {1898-2263}, mesh = {Adolescent ; Azo Compounds/metabolism ; Coloring Agents/metabolism ; Enterocytozoon/genetics/*isolation &amp; purification/metabolism ; Eosine Yellowish-(YS)/metabolism ; Feces/parasitology ; Female ; Humans ; Liver Transplantation ; Methyl Green/metabolism ; Microsporidiosis/diagnosis/immunology/*parasitology ; Molecular Sequence Data ; Phylogeny ; Poland ; Polymerase Chain Reaction ; }, abstract = {Microsporidia are intracellular parasites that cause opportunistic infections in humans of various immunological status. Only a few case reports exist on microsporidial infection in solid organ transplant recipients worldwide. The presented study demonstrates the first case in Poland of Enterocytozoon bieneusi infection in a liver transplant patient. Parasites were diagnosed in stool samples using both modified trichrome staining and PCR.}, }
@article {pmid23768558, year = {2013}, author = {Vrieze, A and de Groot, PF and Kootte, RS and Knaapen, M and van Nood, E and Nieuwdorp, M}, title = {Fecal transplant: a safe and sustainable clinical therapy for restoring intestinal microbial balance in human disease?.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {27}, number = {1}, pages = {127-137}, doi = {10.1016/j.bpg.2013.03.003}, pmid = {23768558}, issn = {1532-1916}, mesh = {Biological Therapy/*methods ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Gastrointestinal Tract/*microbiology ; Host-Pathogen Interactions/*physiology ; Humans ; Metagenome/*physiology ; Probiotics ; }, abstract = {Recent studies have suggested an association between intestinal microbiota composition and human disease, however causality remains to be proven. With hindsight, the application of fecal transplantation (FMT) does indeed suggest a causal relation between interfering with gut microbiota composition and a resultant cure of several disease states. In this review, we aim to show the available evidence regarding the involvement of intestinal microbiota and human (autoimmune) disease. Moreover, we refer to (mostly case report) studies showing beneficial or adverse effects of fecal transplantation on clinical outcomes in some of these disease states. If these findings can be substantiated in larger randomized controlled double blind trials also implementing gut microbiota composition before and after intervention, fecal transplantation might provide us with novel insights into causally related intestinal microbiota, that might be serve as future diagnostic and treatment targets in human disease.}, }
@article {pmid23765468, year = {2013}, author = {Mole, B}, title = {FDA gets to grips with faeces.}, journal = {Nature}, volume = {498}, number = {7453}, pages = {147-148}, doi = {10.1038/498147a}, pmid = {23765468}, issn = {1476-4687}, mesh = {Clostridioides difficile ; Drug Approval/*legislation &amp; jurisprudence ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Humans ; Intestines/*microbiology ; Transplantation/adverse effects/*legislation &amp; jurisprudence/*methods ; United States ; United States Food and Drug Administration/*legislation &amp; jurisprudence ; }, }
@article {pmid23752359, year = {2012}, author = {}, title = {Fecal Transplant for Clostridium difficile-Reply.}, journal = {Archives of internal medicine}, volume = {172}, number = {10}, pages = {825-826}, doi = {10.1001/archinternmed.2012.1413}, pmid = {23752359}, issn = {1538-3679}, }
@article {pmid23735045, year = {2013}, author = {Rogers, GB and Bruce, KD}, title = {Challenges and opportunities for faecal microbiota transplantation therapy.}, journal = {Epidemiology and infection}, volume = {141}, number = {11}, pages = {2235-2242}, pmid = {23735045}, issn = {1469-4409}, mesh = {Clostridioides difficile/*physiology ; Clostridium Infections/*therapy ; Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; }, abstract = {The incidence, morbidity, and mortality associated with Clostridium difficile gastrointestinal infections has increased greatly over recent years, reaching epidemic proportions; a trend due, in part, to the emergence of hypervirulent and antibiotic-resistant strains. The need to identify alternative, non-antibiotic, treatment strategies is therefore urgent. The ability of bacteria in faecal matter transplanted from healthy individuals to displace pathogen populations is well recognized. Further, there is growing evidence that such faecal microbiota transplantation can be of benefit in a wide range of conditions associated with gut dysbiosis. Recent technical advances have greatly increased our ability to understand the processes that underpin the beneficial changes in bacterial community composition, as well as to characterize their extent and duration. However, while much of the research into faecal microbiota transplantation focuses currently on achieving clinical efficacy, the potential for such therapies to contribute to the transmission of infective agents also requires careful consideration.}, }
@article {pmid23734610, year = {2013}, author = {Bertrand, D and Pallet, N and Sartorius, A and Zahar, JR and Soussan, RS and Lortholary, O and Legendre, C and Mamzer, MF}, title = {Clinical and microbial impact of screening kidney allograft preservative solution for bacterial contamination with high-sensitivity methods.}, journal = {Transplant international : official journal of the European Society for Organ Transplantation}, volume = {26}, number = {8}, pages = {795-799}, doi = {10.1111/tri.12130}, pmid = {23734610}, issn = {1432-2277}, mesh = {Adult ; Aged ; Allografts ; Anti-Bacterial Agents/therapeutic use ; Carrier State/epidemiology ; *Drug Contamination ; Enterobacteriaceae/*isolation &amp; purification ; Female ; Humans ; *Kidney Transplantation ; Male ; Middle Aged ; Organ Preservation Solutions/*standards ; Retrospective Studies ; Surgical Wound Infection/*prevention &amp; control ; beta-Lactamases/biosynthesis ; }, abstract = {The clinical and bacteriological consequences of routinely performing highly sensitive bacterial screening of kidney transplant preservation solution (PS) are not known. To evaluate the clinical and microbiological impacts of this strategy, we retrospectively analyzed 200 consecutive kidney allograft recipients from March 2009 to February 2011 for whom PS samples were routinely screened. PS were inoculated into aerobic and anaerobic blood culture bottles, as well as blood agar plates. A rectal swab for extended-spectrum β-lactamase-producing Enterobacteriaceae (EBSL-PE) faecal carriage was also routinely obtained from each patient at admission and every 7 days until hospital discharge. In addition, a standard culture of drain fluid was collected on the day after kidney transplantation. Complete samples and cultures of PS were performed in 165 cases (82.5%), and 62 (37.6%) had positive blood culture results. The most frequent microbial agent isolated was coagulase-negative staphylococci (51.8%). Of these 62 positive samples, only seven (11.3%) were confirmed to contain the same organism by the standard culture method. Drain fluid and PS culture positivity with the same microorganism occurred in only two patients. Of the 62 patients with positive PS cultures, 26 (41.9%) received pre-emptive antibiotic therapy initiated within 48 h post-transplant. During the hospitalization period, patients with a positive PS culture, regardless of whether they received pre-emptive antibiotic therapy, did not exhibit any invasive infections (urinary, blood, peritoneal or wound) related to the microorganisms isolated in the PS. Patients with positive PS cultures who were treated with antibiotic therapy acquired significantly more colonizing ESBL-PE than patients who did not receive antibiotics (53.8% vs. 16.6%; P = 0.01); these patients also developed more clinical infections related to the ESBL-PE (23.1% vs. 5.2%; P < 0.01). The use of antibiotics for patients with positive PS cultures was an independent risk factor for ESBL-PE acquisition in both univariate and multivariate analyses. In conclusion, the use of more sensitive culture methods increases the rate of bacterial contamination of PS and is associated with an increased prescription of antibiotics and increased ESBL-PE carriage and related infections. Therefore, the systematic use of PS blood bottle cultures in kidney transplantation may have no benefit and might increase the rate of ESBL-PE emergence.}, }
@article {pmid25755486, year = {2013}, author = {Aggarwal, R}, title = {Hepatitis e: epidemiology and natural history.}, journal = {Journal of clinical and experimental hepatology}, volume = {3}, number = {2}, pages = {125-133}, pmid = {25755486}, issn = {0973-6883}, abstract = {Hepatitis E is a disease caused by infection with hepatitis E virus (HEV). The virus has four genotypes, named 1 to 4, with one shared serotype. Genotypes 1 and 2 infect only humans, whereas genotypes 3 and 4 primarily infect several mammalian animals, with occasional transmission to humans. Evidence of infection with HEV has been found in most parts of the world, with two distinct epidemiological patterns. In areas with high disease endemicity, primarily developing countries in Asia and Africa, the disease occurs as outbreaks and as sporadic cases of acute hepatitis, and is caused exclusively by infection with genotypes 1 or 2 HEV, which is acquired through fecal-oral route, usually through contamination of water supplies. The disease in these areas occurs most commonly in young adults, and is particularly severe in pregnant women and persons with pre-existing chronic liver disease; chronic infection has not been reported. In areas with lower endemicity, which are mainly developed areas with robust water supply and sanitation systems, occasional sporadic cases of locally-acquired genotype 3 or 4 HEV infection are observed. The affected persons are often elderly and have other coexisting illnesses. The reservoir of infection in these areas is believed to be in animals, such as pigs, wild boar and deer, with zoonotic transmission to humans, possibly through consumption of undercooked meat. Also, in these areas, persistent HEV infection has been well documented among immunosuppressed persons such as organ transplant recipients, and is believed to lead to chronic liver injury, including liver cirrhosis. Further work is needed to better understand the biological basis underlying these widely-differing epidemiological patterns.}, }
@article {pmid23718644, year = {2014}, author = {Wang, TF and Wen, SH and Yang, KL and Yang, SH and Yang, YF and Chang, CY and Wu, YF and Chen, SH}, title = {Reasons for exclusion of 6820 umbilical cord blood donations in a public cord blood bank.}, journal = {Transfusion}, volume = {54}, number = {1}, pages = {231-237}, doi = {10.1111/trf.12269}, pmid = {23718644}, issn = {1537-2995}, mesh = {Blood Banks/organization &amp; administration/statistics &amp; numerical data ; *Blood Donors/statistics &amp; numerical data ; Efficiency, Organizational ; Female ; *Fetal Blood ; Humans ; Infant, Newborn ; Infant, Premature/blood ; Meconium/physiology ; *Patient Selection ; Pregnancy ; Pregnancy Complications/blood/epidemiology ; Public Sector ; Blood Banking/*methods ; }, abstract = {BACKGROUND: To provide information for umbilical cord blood (UCB) banks to adopt optimal collection strategies and to make UCB banks operate efficiently, we investigated the reasons for exclusion of UCB units in a 3-year recruitment period.<br><br>STUDY DESIGN AND METHODS: We analyzed records of the reasons for exclusion of the potential UCB donation from 2004 to 2006 in the Tzu-Chi Cord Blood Bank and compared the results over 3 years. We grouped these reasons for exclusion into five phases, before collection, during delivery, before processing, during processing, and after freezing according to the time sequence and analyzed the reasons at each phase.<br><br>RESULTS: Between 2004 and 2006, there were 10,685 deliveries with the intention of UCB donation. In total, 41.2% of the UCB units were considered eligible for transplantation. The exclusion rates were 93.1, 48.4, and 54.1% in 2004, 2005, and 2006, respectively. We excluded 612 donations from women before their child birth, 133 UCB units during delivery, 80 units before processing, 5010 units during processing, and 421 units after freezing. There were 24 UCB units with unknown reasons of ineligibility. Low UCB weight and low cell count were the first two leading causes of exclusion (48.6 and 30.9%). The prevalence of artificial errors, holiday or transportation problem, low weight, and infant problems decreased year after year.<br><br>CONCLUSION: The exclusion rate was high at the beginning of our study as in previous studies. Understanding the reasons for UCB exclusion may help to improve the efficiency of UCB banking programs in the future.}, }
@article {pmid23689775, year = {2013}, author = {Elopre, L and Rodriguez, M}, title = {Fecal microbiota therapy for recurrent Clostridium difficile infection in HIV-infected persons.}, journal = {Annals of internal medicine}, volume = {158}, number = {10}, pages = {779-780}, pmid = {23689775}, issn = {1539-3704}, support = {K23 MH112417/MH/NIMH NIH HHS/United States ; }, mesh = {Acquired Immunodeficiency Syndrome/*complications ; *Clostridioides difficile ; Clostridium Infections/complications/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; *Metagenome ; Middle Aged ; Recurrence ; }, abstract = {We report 2 cases of successful use of fecal microbiota therapy (fecal transplant) for recurrent Clostridium difficile infection in HIV-infected individuals. Both patients had many recurrences despite antibiotic therapy and improved after receiving fecal microbiota from healthy donors. Recurrent Clostridium difficile infection (CDI) is a common and difficult to manage problem. The risk of recurrence after a first episode is estimated to be around 20–30%, and is even higher after second or later recurrences[[1]]. A disrupted fecal microbiota from previous use of antibiotics plays a major role in recurrent CDI[[1]]. Because of the high rate of recurrence, many different treatment alternatives have been proposed[[1]]. In recent years several cases of successful use of fecal microbiota therapy (FMT) in the treatment of recurrent CDI have been published, with a reported success rate over 90% [[1]]. Here we present what to our knowledge is the first report of FMT in HIV-infected individuals.}, }
@article {pmid23669309, year = {2013}, author = {De Leon, LM and Watson, JB and Kelly, CR}, title = {Transient flare of ulcerative colitis after fecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {11}, number = {8}, pages = {1036-1038}, doi = {10.1016/j.cgh.2013.04.045}, pmid = {23669309}, issn = {1542-7714}, mesh = {Aged ; Biological Therapy/*adverse effects/*methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; Colitis, Ulcerative/*pathology ; Humans ; Male ; }, abstract = {Clostridium difficile infection (CDI) is a common cause of infectious diarrhea and is usually treated with metronidazole or vancomycin. CDI recurs in 15%-30% of patients after the initial episode and in up to 65% after a second episode. Recurrent infections are a challenge to treat, and patients are usually managed with prolonged pulsed or tapered vancomycin. Fecal microbiota transplantation is an alternative treatment that has a 91% rate of success worldwide, with no reported complications. We describe a patient with ulcerative colitis that had been quiescent for more than 20 years who developed a flare of ulcerative colitis after fecal microbiota transplantation, indicating the need for caution in treating CDI with fecal microbiota transplantation in patients with inflammatory bowel disease.}, }
@article {pmid23652911, year = {2013}, author = {Andromanakos, NP and Filippou, DK and Pinis, SI and Kostakis, AI}, title = {Anorectal incontinence: a challenge in diagnostic and therapeutic approach.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {25}, number = {11}, pages = {1247-1256}, doi = {10.1097/MEG.0b013e328361dcfd}, pmid = {23652911}, issn = {1473-5687}, mesh = {Anal Canal/injuries/*physiopathology/surgery ; Catheter Ablation/methods ; Electric Stimulation Therapy/methods ; Fecal Incontinence/*etiology/physiopathology/therapy ; Humans ; Magnetic Field Therapy/methods ; Muscle, Skeletal/transplantation ; Pelvic Floor/surgery ; Rectal Prolapse/complications/surgery ; }, abstract = {Anorectal incontinence is a symptom of a complex multifactorial disorder involving the pelvic floor and anorectum, which is a severe disability and a major social problem. Various causes may affect the anatomical and functional integrity of the pelvic floor and anorectum, leading to the anorectal continence disorder and incontinence. The most common cause of anorectal incontinence is injury of the sphincter muscles following delivery or anorectal surgeries. Although the exact incidence of anorectal incontinence is unknown, various studies suggest that it affects ~2.2-8.3% of adults, with a significant prevalence in the elderly (>50%). The successful treatment of anorectal incontinence depends on the accurate diagnosis of its cause. This can be achieved by a thorough assessment of patients. The management of incontinent patients involves conservative therapeutic procedures, surgical techniques, and minimally invasive approaches.}, }
@article {pmid23643518, year = {2013}, author = {Carabarin-Lima, A and González-Vázquez, MC and Rodríguez-Morales, O and Baylón-Pacheco, L and Rosales-Encina, JL and Reyes-López, PA and Arce-Fonseca, M}, title = {Chagas disease (American trypanosomiasis) in Mexico: an update.}, journal = {Acta tropica}, volume = {127}, number = {2}, pages = {126-135}, doi = {10.1016/j.actatropica.2013.04.007}, pmid = {23643518}, issn = {1873-6254}, mesh = {Animals ; Chagas Disease/*epidemiology/prevention &amp; control ; Humans ; Mexico/epidemiology ; Neglected Diseases ; Protozoan Vaccines ; }, abstract = {Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi, a flagellated organism that is transmitted mainly to humans through the infected feces of triatomine kissing bugs (vector transmission in endemic areas) or by transfusion of infected blood, donations of infected organ, or transmission from an infected mother to her child at birth. Chagas disease was first described in 1909 by the Brazilian physician Carlos Chagas, and due to the parasite's distribution throughout North, Central and South America, the disease is commonly known as American trypanosomiasis. However, this disease is now present in non-endemic countries such as Canada, the United States of America, and several countries in Europe (principally Spain). Moreover, Chagas disease was recently designated by the World Health Organization as one of the main neglected tropical diseases. The aim of this review is to summarize the research efforts recently described in studies conducted in Mexico on Chagas disease. In this country, there are no existing vector control programs. In addition, there is no consensus on the diagnostic methods for acute and chronic Chagas disease in maternity wards and blood banks, and trypanocidal therapy is not administered to chronic patients. The actual prevalence of the disease is unknown because no official reporting of cases is performed. Therefore, the number of people infected by different routes of transmission (vector, congenital, blood transfusion, organ transplantation, or oral) is unknown. We believe that by promoting education about Chagas disease in schools starting at the basic elementary level and including reinforcement at higher education levels will ensure that the Mexican population would be aware of this health problem and that the control measures adopted will have more acceptance and success. We hope that this review sensitizes the relevant authorities and that the appropriate measures to reduce the risk of infection by T. cruzi are undertaken to provide the Mexican people a better quality of life.}, }
@article {pmid23642791, year = {2013}, author = {Brandt, LJ and Aroniadis, OC}, title = {An overview of fecal microbiota transplantation: techniques, indications, and outcomes.}, journal = {Gastrointestinal endoscopy}, volume = {78}, number = {2}, pages = {240-249}, doi = {10.1016/j.gie.2013.03.1329}, pmid = {23642791}, issn = {1097-6779}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Inflammatory Bowel Diseases/therapy ; Irritable Bowel Syndrome/therapy ; *Microbiota ; Patient Selection ; Recurrence ; Transplantation/*methods ; }, }
@article {pmid23640146, year = {2013}, author = {Wyrick, S and Couloures, KG and Dupuis, GM and Williams, RS}, title = {Hyperkalemia and ventricular tachycardia after outpatient ureteral valve reimplantation: a case report.}, journal = {Pediatric emergency care}, volume = {29}, number = {5}, pages = {650-652}, doi = {10.1097/PEC.0b013e31828ec00a}, pmid = {23640146}, issn = {1535-1815}, mesh = {Abdominal Pain/etiology ; Acute Kidney Injury/blood/*etiology ; Ambulatory Surgical Procedures ; Circumcision, Male ; Emergencies ; Fecal Impaction/etiology ; Humans ; Hydronephrosis/etiology/therapy ; Hyperkalemia/*etiology ; Infant ; Male ; Postoperative Complications/diagnosis/*etiology/therapy ; Postoperative Nausea and Vomiting/etiology ; Reoperation ; Replantation ; Tachycardia, Ventricular/*etiology ; Ureter/*surgery ; Ureteral Obstruction/blood/*etiology ; Urinary Catheterization ; Vesico-Ureteral Reflux/surgery ; }, abstract = {OBJECTIVE: This study aimed to report on a toddler who presented with progressively worsening abdominal pain and obstructive uropathy 1 week after ureteral valve reimplantation. Acute renal failure resulted in critical hyperkalemia.<br><br>METHODS: Chart review of presentation, physical examination, laboratory tests, and treatment.<br><br>RESULTS: Initial potassium level was 10 mEq/L; ventricular tachycardia was observed and treated.<br><br>CONCLUSIONS: More commonly, hyperkalemia results from overuse/overdose of supplementation or in patients with known renal failure. Although less common, obstructive uropathy should be considered in any patient with recent instrumentation of the urinary tract and coincident complications can be significant.}, }
@article {pmid23639085, year = {2013}, author = {Allen-Vercoe, E and Petrof, EO}, title = {Artificial stool transplantation: progress towards a safer, more effective and acceptable alternative.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {7}, number = {4}, pages = {291-293}, doi = {10.1586/egh.13.16}, pmid = {23639085}, issn = {1747-4132}, mesh = {Anti-Bacterial Agents/therapeutic use ; Biological Therapy/*methods ; Clostridioides difficile/*pathogenicity ; *Colonoscopy ; Diarrhea/diagnosis/microbiology/*therapy ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*therapy ; Feces/*microbiology ; Humans ; Recurrence ; Severity of Illness Index ; Treatment Outcome ; }, }
@article {pmid23632358, year = {2013}, author = {Weingarden, AR and Hamilton, MJ and Sadowsky, MJ and Khoruts, A}, title = {Resolution of severe Clostridium difficile infection following sequential fecal microbiota transplantation.}, journal = {Journal of clinical gastroenterology}, volume = {47}, number = {8}, pages = {735-737}, pmid = {23632358}, issn = {1539-2031}, support = {R21 AI091907/AI/NIAID NIH HHS/United States ; }, mesh = {Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Follow-Up Studies ; Humans ; Male ; Severity of Illness Index ; Treatment Outcome ; }, }
@article {pmid23627849, year = {2013}, author = {Borody, TJ and Brandt, LJ and Paramsothy, S and Agrawal, G}, title = {Fecal microbiota transplantation: a new standard treatment option for Clostridium difficile infection.}, journal = {Expert review of anti-infective therapy}, volume = {11}, number = {5}, pages = {447-449}, doi = {10.1586/eri.13.26}, pmid = {23627849}, issn = {1744-8336}, mesh = {Anti-Bacterial Agents/adverse effects ; Biological Therapy/*methods ; Clostridioides difficile/drug effects/pathogenicity/physiology ; Enterocolitis, Pseudomembranous/microbiology/physiopathology/*therapy ; Feces/*microbiology ; Humans ; Metagenome/*physiology ; }, }
@article {pmid23624888, year = {2013}, author = {Kahn, SA and Vachon, A and Rodriquez, D and Goeppinger, SR and Surma, B and Marks, J and Rubin, DT}, title = {Patient perceptions of fecal microbiota transplantation for ulcerative colitis.}, journal = {Inflammatory bowel diseases}, volume = {19}, number = {7}, pages = {1506-1513}, pmid = {23624888}, issn = {1536-4844}, support = {UL1 RR024999/RR/NCRR NIH HHS/United States ; KL2TR000431/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biological Therapy/*methods ; Colitis, Ulcerative/microbiology/psychology/*therapy ; Feces/*microbiology ; Female ; Follow-Up Studies ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; *Microbiota ; Middle Aged ; *Perception ; Prognosis ; *Transplantation ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT), the delivery of stool from a healthy prescreened donor to an individual with disease, is gaining increasing recognition as a potential treatment for inflammatory bowel diseases. Our objective was to describe patient interest in and social concerns around FMT.<br><br>METHODS: We conducted a survey of adults with ulcerative colitis (UC) seen in outpatient clinic at the University of Chicago IBD Center. All English-speaking patients &#x2265;18 years of age were eligible. Subjects completed a written survey in clinic. Ninety-five participants, median age 39 years, 53% female, were enrolled in the study.<br><br>RESULTS: Forty-four percent and 49% reported excellent or good/satisfactory medical management of their UC, respectively. Forty-six percent participants were willing to undergo FMT as a treatment of UC, 43% were unsure, and 11% were unwilling to undergo FMT. Subjects who had been hospitalized were more willing to undergo FMT, 54% versus 34%, P = 0.035. Primary concerns included the following: adequate screening for infections (41%), cleanliness (24%), and potential to worsen UC (18%); 21% reported no specific concerns. For donor selection, an equal number of participants (46%) preferred whomever their doctor recommended or family member/spouse.<br><br>CONCLUSIONS: In our center despite reporting satisfactory to excellent disease control with their treatments, the vast majority of patients with UC are interested in or willing to consider FMT. Proof of safety and effectiveness, and failure of other medical therapies are key issues in considering FMT. Strong interest in this as-yet unproven therapy warrants attention and is a pressing priority for clinical research and education.}, }
@article {pmid23622693, year = {2013}, author = {Bourlioux, P}, title = {[Which alternatives are at our disposal in the anti-infectious therapeutics face to multi-drug resistant bacteria?].}, journal = {Annales pharmaceutiques francaises}, volume = {71}, number = {3}, pages = {150-158}, doi = {10.1016/j.pharma.2013.02.005}, pmid = {23622693}, issn = {0003-4509}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology/*therapeutic use ; Bacterial Infections/*drug therapy/microbiology ; Bacterial Vaccines ; Bacteriophages ; Chemistry, Pharmaceutical ; Drug Delivery Systems ; Drug Resistance, Multiple, Bacterial/*drug effects ; Honey ; Humans ; Larva ; }, abstract = {The development of multi-drug resistance to antibiotics during the last years and the few number of new active molecules launched on the market have limited the treatment of some infectious diseases. Which alternatives are at our disposal in the anti-infectious therapeutics face to multi-drug resistant bacteria? Considering the bibliographic data, we can note different facts: (1) some alternatives already exist, but correspond more to targeted useful and usable therapeutics as phage therapy, honey therapy, or maggot therapy; (2) some "old" antibiotics can find new bacterial targets and reinforce the anti-infectious therapy towards some multi-drug resistant bacteria; (3) new formulations can allow targeted drug delivery via nanoparticles and the association of molecules can reinforce the antibiotic antimicrobial effect; (4) new treatment could be potentially usable as: antimicrobial peptides, probiotics, herbal medicines, statins, phosphonosulfonates, fecal transplants...; (5) at least, we must not forget that "it's better to prevent than cure". So, besides the principles of hygiene that must be respected, it is necessary to promote (if possible) the development of new vaccines against bacteria responsible for nosocomial infections. Facing with this potential, we can say that new orientations are open with very different levels of success and that it is urgent to find new targets ignored or forgotten until now.}, }
@article {pmid23621738, year = {2013}, author = {Us, D}, title = {[New, newer, newest human polyomaviruses: how far?].}, journal = {Mikrobiyoloji bulteni}, volume = {47}, number = {2}, pages = {362-381}, doi = {10.5578/mb.5377}, pmid = {23621738}, issn = {0374-9096}, mesh = {Animals ; Humans ; Polyomavirus/*classification/pathogenicity ; Polyomavirus Infections/epidemiology/*virology ; Tumor Virus Infections/epidemiology/*virology ; Vertebrates ; }, abstract = {Polyomaviruses, classified in Polyomaviridae family, are non-enveloped small (40-45 nm) viruses with icosahedral symmetry and circular double-stranded DNA genome. Polyomaviruses can infect a variety of vertebrates including birds, rodents, cattle, monkeys and humans. The characteristics such as establishment of latent infections, reactivations during immunosuppression and oncogenic potencies render the human polyomaviruses (HPyVs) of considerable importance for public health. The first polyomavirus (Mouse polyomavirus) has been identified in 1953 as filterable tumor-causing agents in mice, followed by Simian vacuolating virus (SV40) isolated from rhesus monkey kidney cells that had been used for poliovirus vaccine preparation in 1960. Due to the known transforming capacity of SV40, it was initially thought that the incidence of cancer could increase following the administration of SV40-contaminated polio vaccines, however advanced studies yielded inconsistent results, without any evidence to conclude whether or not the contaminated polio vaccine caused cancer. Several studies have reported the detection of SV40 genome in some of the human tumors, as well as in the clinical samples of healthy subjects. In addition SV40 seropositivity was reported in human populations although in low rates (2-10%). These data have raised the possibility that SV40 infects humans and circulates in human populations unrelated to being exposed to the vaccine. The discovery of the first human polyomaviruses was in 1971 independently from each other, one was BK virus (BKPyV) isolated from the urine sample of a renal transplant patient, and the other was JC virus (JCPyV) isolated from the brain tissue of a patient with progressive multifocal leukoencephalopathy, and both were named after the patients' initials. BK and JC viruses were the only well-known human polyomaviruses throughout 36 years, however drammatical increase in number of newly identified human polyomaviruses was recorded in the last six years due to the use of sophisticated molecular methods and new-generation sequencing technologies. In 2007, two new HPyVs were identified independently from nasopharyngeal aspirates of children with acute respiratory tract infections; one was KI (Karolinska Institute) and the other was WU (Washington University) polyomaviruses, named after the initials of institutes which they were first described. In 2008, the fifth HPyV namely Merkel cell polyomavirus (MCPyV) was isolated from the skin tumor sample of a patient with Merkel cell carcinoma. In 2010, three other novel human polyomaviruses were discovered, two were from skin samples of healthy subjects (HPyV-6 and HPyV-7), and one (Trichodysplasia Spinulosa-associated virus; TSPyV) from keratotic spicule sample of a heart-transplanted patient. Another new HPyV was identified in 2011 named HPyV-9, from the blood and urine samples of an asymptomatic patient with kidney transplant. Most recently, three new HPyVs have been sequentially discovered during the last quarter of 2012. The 10th HPyV (HPyV10) was identified in condyloma samples of an immunocompromised patient with WHIM syndrome (Wart, Hypogammaglobulinemia, Infections, Myelokathexis), 11th virus was isolated from stool sample of a healthy child from Malawi (Malawi polyomavirus; MWPyV), and 12th was described from fecal sample of a diarrheal child from Mexico (Mexico polyomavirus; MXPyV). The whole genome sequence analysis of HPyV10, MWPyV and MXPyV pointed out that they are closely related viruses. The last novel polyomavirus, namely Saint Louis polyomavirus (STLPyV) has been reported in a study published on February 2013, identified from the stool sample of a healthy child. Seroepidemiological studies indicated that most of the novel HPyVs are highly prevalent (average rate: 40-80%) worldwide and likely acquired asymptomatically during childhood, similar to the old ones, BKPyV and JCPyV. However data about HPyV10, MWPyV, MXPyV and STLPyV are not enough as they have been discovered most recently. Similarly, little is known about the pathogenesis, route of infection and the relationship with clinical diseases of novel HPyVs except MCPyV and TSPyV which are known to be responsible for Merkel cell carcinoma and trichodysplasia spinulosa, respectively. The expanding repertoire of human polyomaviruses made us think that many others will be uncovered in the future thanking to the advances in molecular methods. In this review, recent developments subjecting new human polyomaviruses have been summarized.}, }
@article {pmid23613218, year = {2013}, author = {Tschuor, C and Limani, P and Nocito, A and Dindo, D and Clavien, PA and Hahnloser, D}, title = {Perineal stapled prolapse resection for external rectal prolapse: is it worthwhile in the long-term?.}, journal = {Techniques in coloproctology}, volume = {17}, number = {5}, pages = {537-540}, pmid = {23613218}, issn = {1128-045X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Fecal Incontinence/etiology/*prevention &amp; control ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures/methods ; Patient Safety ; Perineum/surgery ; Proctoscopy/*methods ; Prospective Studies ; Rectal Prolapse/complications/diagnosis/*surgery ; Rectum/*surgery ; Recurrence ; Reoperation ; Risk Assessment ; Severity of Illness Index ; Surgical Stapling/*methods ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Perineal stapled prolapse (PSP) resection is a novel operation for treating external rectal prolapse. However, no long-term results have been reported in the literature. This study analyses the long-term recurrence rate, functional outcome, and morbidity associated with PSP resection.<br><br>METHODS: Nine consecutive patients undergoing PSP resection between 2007 and 2011 were prospectively followed. Surgery was performed by the same surgeons in a standardised technique. Recurrence rate, functional outcome, and complication grade were prospectively assessed.<br><br>RESULTS: All 9 patients undergoing PSP resection were investigated. The median age was 72 years (range 25-88 years). No intraoperative complications occurred. Faecal incontinence, preoperatively present in 2 patients, worsened postoperatively in one patient (Vaizey 18-22). One patient developed new-onset faecal incontinence (Vaizey 18). The median obstructive defecation syndrome score decreased postoperatively significantly from 11 (median; range 8-13) to 5 (median; range 4-8) (p < 0.005). At a median follow-up of 40 months (range 14-58 months), the prolapse recurrence rate was 44 % (4/9 patients).<br><br>CONCLUSIONS: The PSP resection is a fast and safe procedure associated with low morbidity. However, the poor long-term functional outcome and the recurrence rate of 44 % warrant a cautious patient selection.}, }
@article {pmid23608595, year = {2013}, author = {Abravanel, F and Lhomme, S and Dubois, M and Peron, JM and Alric, L and Kamar, N and Izopet, J}, title = {Hepatitis E virus.}, journal = {Medecine et maladies infectieuses}, volume = {43}, number = {7}, pages = {263-270}, doi = {10.1016/j.medmal.2013.03.005}, pmid = {23608595}, issn = {1769-6690}, mesh = {Animals ; Antibodies, Viral/blood ; Antiviral Agents/therapeutic use ; Developing Countries ; Feces/virology ; Female ; Genome, Viral ; Hepatitis E/diagnosis/*epidemiology/prevention &amp; control/therapy/transmission/veterinary/virology ; Hepatitis E virus/classification/genetics/*physiology ; Hepatitis, Viral, Animal/epidemiology/transmission/virology ; Humans ; Immunocompromised Host ; Immunoglobulin M/blood ; Liver Transplantation ; Male ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology/virology ; RNA, Viral/genetics ; Swine ; Swine Diseases/epidemiology/transmission/virology ; Transfusion Reaction ; Viral Hepatitis Vaccines ; Water Microbiology ; Water Pollution ; Zoonoses ; }, abstract = {Hepatitis E virus (HEV) is responsible for major outbreaks of acute hepatitis in developing countries where it was first described as a waterborne disease, transmitted by drinking water contaminated with feces. Attention was focused on HEV in developed countries and its associated diseases in recent years as a result of increasing reports of autochthonous infections. Hepatitis E is the zoonotic cause of these acute infections, and mainly in men over 50 years of age. The clinical manifestations and laboratory abnormalities of hepatitis E infections in immunocompetent patients cannot be distinguished from those caused by other hepatitis viruses. HEV is a major public health concern in immunocompromised patients because their infections can become chronic. The specific etiology of cases of hepatitis E infection can be diagnosed by serological testing and detecting viral RNA. Ribavirin is currently the reference treatment for HEV infections in immunocompromised patients. Several vaccines have proved safe and effective in clinical trials, but none have been approved for use in Europe yet.}, }
@article {pmid23594389, year = {2013}, author = {Van den Abbeele, P and Verstraete, W and El Aidy, S and Geirnaert, A and Van de Wiele, T}, title = {Prebiotics, faecal transplants and microbial network units to stimulate biodiversity of the human gut microbiome.}, journal = {Microbial biotechnology}, volume = {6}, number = {4}, pages = {335-340}, pmid = {23594389}, issn = {1751-7915}, mesh = {*Biodiversity ; Biological Therapy/*methods ; Diet/*methods ; Gastrointestinal Tract/*microbiology ; Humans ; *Microbiota ; *Prebiotics ; }, abstract = {Accumulating evidence demonstrates the intimate association between human hosts and the gut microbiome. Starting at birth, the sterile gut of the newborn acquires a diverse spectrum of microbes, needed for immunological priming. However, current practices (caesarean sections, use of formula milk) deprive newborns from being exposed to this broad spectrum of microbes. Unnecessary use of antibiotics and excessive hygienic precautions (e.g. natural versus chlorinated drinking water) together with the Western diet further contribute to a decreased microbial diversity in the adult gut. This has been correlated with recurrent Clostridium difficile infection, inflammatory bowel diseases and obesity, among others. A healthy gut microbiome is thus characterized by a diverse network of metabolically interacting microbial members. In this context, we review several existing and novel approaches to manage the gut microbiome. First, prebiotic compounds should be re-defined in the sense that they should enhance the ecological biodiversity rather than stimulating single species. Recent studies highlight that structurally different polysaccharides require specific primary degraders but also enhance a similar network of secondary degraders that benefit from cross-feeding. A faecal transplantation is a second approach to restore biodiversity when the microbiota is severely dysbiosed, with promising results regarding C. difficile-associated disease and obesity-related metabolic syndromes. A final strategy is the introduction of key microbial network units, i.e. pre-organized microbial associations, which strengthen the overall microbial network of the gut microbiome that supports human health.}, }
@article {pmid23593356, year = {2013}, author = {Kotkova, M and Sak, B and Kvetonova, D and Kvac, M}, title = {Latent microsporidiosis caused by Encephalitozoon cuniculi in immunocompetent hosts: a murine model demonstrating the ineffectiveness of the immune system and treatment with albendazole.}, journal = {PloS one}, volume = {8}, number = {4}, pages = {e60941}, pmid = {23593356}, issn = {1932-6203}, mesh = {Albendazole/*therapeutic use ; Animals ; Chlorocebus aethiops ; Dexamethasone ; *Disease Models, Animal ; *Encephalitozoon cuniculi ; Encephalitozoonosis/*drug therapy/*immunology ; Feces/microbiology ; Flow Cytometry ; Lymphocyte Count ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Polymerase Chain Reaction ; Vero Cells ; Viscera/microbiology ; }, abstract = {BACKGROUND: Microsporidia are obligate intracellular parasites causing severe infections with lethal outcome in immunocompromised hosts. However, these pathogens are more frequently reported as latent infections in immunocompetent individuals and raises questions about the potential risk of reactivation following induced immunosuppression.<br><br>AIMS: To evaluate the possibility latent microsporidiosis, efficacy or albendazole, and reactivation, the authors monitored the course of E. cuniculi infection in immunocompetent BALB/c mice and immunodeficient SCID mice using molecular methods.<br><br>METHODS: Mice were per orally infected with 10(7) spores of E. cuniculi. Selected groups were treated with albendazole, re-infected or chemically immunosuppressed by dexamethasone. The presence of microsporidia in the host's organs and feces were determined using PCR methods. Changes in numbers of lymphocytes in blood and in spleen after induction of immunosuppression were confirmed using flow cytometry analysis.<br><br>RESULTS: Whereas E. cuniculi caused lethal microsporidiosis in SCID mice, the infection in BABL/c mice remained asymptomatic despite parasite dissemination into many organs during the acute infection phase. Albendazole treatment led to microsporidia elimination from organs in BALB/c mice. In SCID mice, however, only a temporary reduction in number of affected organs was observed and infection re-established post-treatment. Dexamethasone treatment resulted in a chronic microsporidia infection disseminating into most organs in BALB/c mice. Although the presence of E. cuniculi in organs of albendazole- treated mice was undetectable by PCR, it was striking that infection was reactivated by immunosuppression treatment.<br><br>CONCLUSION: Our results demonstrated that microsporidia can successfully survive in organs of immunocompetent hosts and are able to reactivate from undetectable levels and spread within these hosts after induction of immunosuppression. These findings stress the danger of latent microsporidiosis as a life-threatening risk factor especially for individuals undergoing chemotherapy and in transplant recipients of organs originating from infected donors.}, }
@article {pmid23575749, year = {2013}, author = {Ettinger, G and Burton, JP and Reid, G}, title = {If microbial ecosystem therapy can change your life, what's the problem?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {6}, pages = {508-512}, doi = {10.1002/bies.201300015}, pmid = {23575749}, issn = {1521-1878}, mesh = {Administration, Rectal ; Animals ; Drug Resistance, Bacterial ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Metagenome ; Ownership ; Probiotics/administration &amp; dosage ; }, abstract = {The increased incidence of morbidity and mortality due to Clostridium difficile infection, had led to the emergence of fecal microbial transplantation (FMT) as a highly successful treatment. From this, a 32 strain stool substitute has been derived, and successfully tested in a pilot human study. These approaches could revolutionize not only medical care of infectious diseases, but potentially many other conditions linked to the human microbiome. But a second revolution may be needed in order for regulatory agencies, society and medical practitioners to accept and utilize these interventions, monitor their long term effects, have a degree of control over their use, or at a minimum provide guidelines for donors and recipients.}, }
@article {pmid23574632, year = {2013}, author = {de Vos, WM}, title = {Fame and future of faecal transplantations--developing next-generation therapies with synthetic microbiomes.}, journal = {Microbial biotechnology}, volume = {6}, number = {4}, pages = {316-325}, pmid = {23574632}, issn = {1751-7915}, mesh = {Biological Therapy/*methods ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; *Microbiota ; Transplantation/*methods ; }, abstract = {While practised for over thousand years, there is presently a renaissance in the interest of using of faecal transplantations to modify the intestinal microbiota of patients. This clinical practice consists of delivering large amounts of bowel microbes in various forms into the intestinal tract of the recipient that usually has been cleared previously. The major reason for the popularity of faecal transplantations is their effectiveness in treating a variety of diseases. Hence, there is a need to develop this procedure to the next level. While there are various developments to select, standardize and store the donor microbiota, it is more challenging to understand the intestinal microbial communities and develop ways to deliver these via robust biotechnological processes. The various approaches that have been followed to do so are discussed in this contribution that is also addressing the concept of the minimal microbiome as well as the production of the synthetic communities that can be instrumental in new therapeutic avenues to modify the intestinal microbiota.}, }
@article {pmid23573537, year = {2013}, author = {Kovacs, G}, title = {[To the Editors, regarding feces transplantation].}, journal = {Orvosi hetilap}, volume = {154}, number = {11}, pages = {434-435}, pmid = {23573537}, issn = {0030-6002}, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; Diarrhea/*microbiology ; Enterocolitis, Pseudomembranous/*therapy ; *Feces ; *Gastrointestinal Tract ; Humans ; Male ; Transplantation, Homologous/*methods ; }, }
@article {pmid23572128, year = {2013}, author = {Kaneko, J and Sugawara, Y and Tamura, S and Aoki, T and Sakamoto, Y and Hasegawa, K and Yamashiki, N and Kokudo, N}, title = {De novo malignancies after adult-to-adult living-donor liver transplantation with a malignancy surveillance program: comparison with a Japanese population-based study.}, journal = {Transplantation}, volume = {95}, number = {9}, pages = {1142-1147}, doi = {10.1097/TP.0b013e318288ca83}, pmid = {23572128}, issn = {1534-6080}, mesh = {Asian People ; Colorectal Neoplasms/*epidemiology/mortality ; Follow-Up Studies ; Humans ; Incidence ; *Liver Transplantation ; *Living Donors ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Organ transplant recipients have an increased incidence of malignancy. Race differences in a variety of malignancies are observed among the general population, but de novo malignancies after adult-to-adult living-donor liver transplantation (LDLT) have not been compared with those from a Japanese population-based study.<br><br>METHODS: The subjects were 360 adult LDLT recipients who survived more than 1 year after transplantation. An annual medical checkup and screening examinations were performed as follows: abdominal computed tomography or magnetic resonance imaging, upper gastrointestinal endoscopy, and total colonoscopy and immunochemical fecal occult blood test every 1 to 2 years. Complete blood count, liver function tests, and several tumor markers were checked every 1 to 3 months after LDLT.<br><br>RESULTS: Mean follow-up period was 7.5&#xb1;3.4 years. During the follow-up period, 27 de novo malignancies were diagnosed in 26 recipients. Colorectal cancer was the most commonly detected malignancy. The overall mortality of the recipients with de novo malignancies was similar to the findings of the Japanese general population-based study (standardized mortality ratio=0.9). Overall, the incidence of cancer was significantly higher in transplant recipients than in the Japanese general population (standardized incidence ratio=1.8). The 5-year estimated survival rate of recipients with de novo malignancies was 81% and those of recipients without malignancies was 93% (P<0.0001).<br><br>CONCLUSIONS: Colorectal malignancies predominated in Japanese liver transplant recipients. Although de novo malignancies correlated with a poor prognosis, the standardized mortality ratio was 0.9 compared with that of subjects of a Japanese population-based study.}, }
@article {pmid23563757, year = {2013}, author = {Gil, FF and Barros, MJ and Macedo, NA and Júnior, CG and Redoan, R and Busatti, H and Gomes, MA and Santos, JF}, title = {Prevalence of intestinal parasitism and associated symptomatology among hemodialysis patients.}, journal = {Revista do Instituto de Medicina Tropical de Sao Paulo}, volume = {55}, number = {2}, pages = {69-74}, doi = {10.1590/s0036-46652013000200001}, pmid = {23563757}, issn = {1678-9946}, mesh = {Adult ; Aged ; Animals ; Brazil/epidemiology ; Case-Control Studies ; Cross-Sectional Studies ; Feces/*parasitology ; Female ; Humans ; Immunocompromised Host ; Intestinal Diseases, Parasitic/diagnosis/*epidemiology/parasitology ; Kidney Failure, Chronic/parasitology/therapy ; Male ; Middle Aged ; Prevalence ; Renal Dialysis/*statistics &amp; numerical data ; }, abstract = {Intestinal parasites are an important cause of morbidity and mortality. Immunocompromised individuals may develop more severe forms of these infections. Taking into account the immunity impairment in patients suffering from chronic renal failure (CRF), we will determine the prevalence and associated symptoms of intestinal parasites in these patients. Controls without CRF were used for comparison. Stool samples were collected and processed for microscopic identification of parasites using the Formalin-ether concentration method. For Cryptosporidium diagnosis, the ELISA technique was used. One hundred and ten fecal samples from hemodialysis patients were analyzed, as well as 86 from a community group used as control group. A result of 51.6% of intestinal parasites was observed in hemodialysis patients and 61.6% in the control group. Cryptosporidium and Blastocystis were the most common infections in patients with CRF (26.4% and 24.5%, respectively). Blastocystis was the most common infection in the control group (41.9%), however no individual was found positive for Cryptosporidium. Among the CRF patients, 73.6% were symptomatic, 54.3% of these tested positive for at least one parasite, in contrast to 44.8% in asymptomatic patients (p = 0.38). The most common symptoms in this group were flatulence (36.4%), asthenia (30.0%) and weight loss (30.0%). In the control group, 91.9% were symptomatic, 60.8% of these tested positive for at least one parasite, in contrast to 71.4% in asymptomatic patients (p = 0.703). A significant difference between the two groups was observed with regard to symptoms, with bloating, postprandial fullness, and abdominal pain being more frequent in the control group than in the hemodialysis group (all p < 0.05). Comparing symptomatic with asymptomatic, there was no association in either group between symptoms or the prevalence of parasitic infection, nor with the type of parasite or with multiple parasitic infections. Patients with chronic renal failure are frequent targets for renal transplantation, which as well as the inherent immunological impairment of the disease itself, results in immunosuppression by medication. For this reason, carriers of intestinal parasites with pathogenic potential can develop serious clinical complications influencing the success of transplantation. This fact, coupled with the high prevalence of intestinal parasites and the dissociation between symptoms and infection in CRF patients, suggests that the stool test should be incorporated in routine propedeutics. Furthermore, preventive measures for the acquisition of parasites through the fecal-oral contamination route should be introduced.}, }
@article {pmid23554205, year = {2013}, author = {Coste, JF and Vuiblet, V and Moustapha, B and Bouin, A and Lavaud, S and Toupance, O and de Rougemont, A and Benejat, L and Megraud, F and Wolak-Thierry, A and Villena, I and Chemla, C and Le Magrex, E and de Champs, C and Andreoletti, L and Rieu, P and Leveque, N}, title = {Microbiological diagnosis of severe diarrhea in kidney transplant recipients by use of multiplex PCR assays.}, journal = {Journal of clinical microbiology}, volume = {51}, number = {6}, pages = {1841-1849}, pmid = {23554205}, issn = {1098-660X}, mesh = {Adolescent ; Adult ; Aged ; Bacterial Infections/diagnosis/microbiology ; Coinfection/diagnosis/microbiology/virology ; Diarrhea/*diagnosis/microbiology/virology ; Feces/*microbiology/*virology ; Female ; Humans ; Immunocompromised Host ; Kidney Transplantation ; Male ; Microbiological Techniques/*methods ; Middle Aged ; Molecular Diagnostic Techniques/*methods ; Molecular Sequence Data ; Multiplex Polymerase Chain Reaction/*methods ; Sequence Analysis, DNA ; Transplantation ; Virus Diseases/diagnosis/virology ; Young Adult ; }, abstract = {Diarrhea is a frequent complication after kidney transplantation, ascribed to adverse effects of the immunosuppressive therapy in case of negative microbiological examination of the stools. The aim of this study was to improve the microbiological diagnosis by implementing molecular tests. Fifty-four severe diarrhea events that occurred in 49 adult kidney transplant recipients from September 2010 to November 2011 were investigated. One or several enteric pathogens were detected in 13 (23%) stool samples using classical microbiological methods versus 39 (72%) for the seven commercially available multiplex PCR assays used retrospectively (P = 0.006). Interestingly, molecular diagnosis identified 15 multiple infections compared to none using classical techniques. The primary pathogens detected were enteropathogenic Escherichia coli (EPEC) (n = 15; 38%), Campylobacter spp. (n = 15; 38%), and Norovirus (n = 14; 36%). Specificities for Campylobacter and Norovirus infection diagnosis were 75 and 100%, respectively, by comparison to reference methods. Based on molecular findings, a cyclosporine-mycophenolate mofetil combination was identified as a risk factor for developing Norovirus-induced diarrhea. Norovirus infections were also responsible for higher weight loss than all the other causes of diarrhea. In samples from asymptomatic immunocompromised and immunocompetent patients, EPEC but not Norovirus and Campylobacter infections were detected at a frequency similar to that observed in symptomatic kidney transplant recipients. In conclusion, molecular tools significantly improved the detection of single and multiple enteric infections by comparison to classical techniques and could quickly become the key element in the management of severe acute diarrhea in transplant recipients.}, }
@article {pmid23550305, year = {2013}, author = {Senior, K}, title = {Faecal transplantation for recurrent C difficile diarrhoea.}, journal = {The Lancet. Infectious diseases}, volume = {13}, number = {3}, pages = {200-201}, doi = {10.1016/s1473-3099(13)70052-5}, pmid = {23550305}, issn = {1474-4457}, mesh = {Biological Therapy ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Recurrence ; }, }
@article {pmid23549961, year = {2013}, author = {Romaniszyn, M and Rozwadowska, N and Nowak, M and Malcher, A and Kolanowski, T and Walega, P and Richter, P and Kurpisz, M}, title = {Successful implantation of autologous muscle-derived stem cells in treatment of faecal incontinence due to external sphincter rupture.}, journal = {International journal of colorectal disease}, volume = {28}, number = {7}, pages = {1035-1036}, pmid = {23549961}, issn = {1432-1262}, mesh = {Anal Canal/*pathology ; Fecal Incontinence/*therapy ; Follow-Up Studies ; Humans ; Male ; Muscles/*cytology ; Rupture/pathology/therapy ; *Stem Cell Transplantation ; Stem Cells/*cytology ; Transplantation, Autologous ; Young Adult ; }, }
@article {pmid23549617, year = {2013}, author = {Suwantarat, N and Bobak, DA}, title = {Fecal Bacteriotherapy for Recurrent Clostridium difficile Infection: What's Old Is New Again?.}, journal = {Current infectious disease reports}, volume = {15}, number = {2}, pages = {101-103}, pmid = {23549617}, issn = {1523-3847}, abstract = {In recent years, effective management of recurrent Clostridium difficile infection (CDI) has emerged as an important issue for those clinicians who treat patients with CDI. In addition to antibiotic-based therapies, including alternating use, chaser, and tapering protocols, interest has increased in the potential utility of a variety of nonantibiotic forms of adjunctive therapy. Among these alternative forms of treatment, the concept of transferring extracts of a stool from donors to patients with CDI has been met with great interest among researchers, clinicians, and patients alike. Fecal bacteriotherapy, or so-called fecal microbiota transplantation, for therapy of CDI is a procedure that dates back to the 1950s. Recently, however, a variety of studies have garnered attention in the lay press, in addition to the standard scientific-reporting community. Although no well-controlled trials have been published as yet and the details of the procedures used have varied widely between institutions, the available evidence suggests that for selected patients, fecal bacteriotherapy appears to be generally safe and effective. Concerns about true efficacy and the theoretical potential for infectious complications have prevented widespread adoption of this concept as standard therapy, but its use in academic and community practices is on the rise.}, }
@article {pmid23549377, year = {2013}, author = {Zhang, Q and Widmer, G and Tzipori, S}, title = {A pig model of the human gastrointestinal tract.}, journal = {Gut microbes}, volume = {4}, number = {3}, pages = {193-200}, pmid = {23549377}, issn = {1949-0984}, support = {R01 AI088748/AI/NIAID NIH HHS/United States ; R56 AI094459/AI/NIAID NIH HHS/United States ; AI094459/AI/NIAID NIH HHS/United States ; AI088748/AI/NIAID NIH HHS/United States ; }, mesh = {Aged ; Animals ; Biota ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Female ; Gastrointestinal Tract/*microbiology ; Germ-Free Life ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Male ; *Metagenome ; Middle Aged ; *Models, Animal ; RNA, Ribosomal, 16S/genetics ; Swine ; Time Factors ; }, abstract = {Easy access to next generation sequencing has enabled the rapid analysis of complex microbial populations. To take full advantage of these technologies, animal models enabling the manipulation of human microbiomes and the study of the impact of such perturbations on the host are needed. To this aim we are developing experimentally tractable and clinically relevant pig models of the human adult and infant gastro-intestinal tract. The intestine of germ-free piglets was populated with human adult or infant fecal microbial populations, and the piglets were maintained on solid or milk diet, respectively. Amplicons of 16S rRNA V6 region were deep-sequenced to monitor to what extent the transplanted human microbiomes changed in the pig. Within 24 h of transfer of human fecal microbiome to pigs, bacterial microbiomes rich in Proteobacteria emerged. These populations evolved toward a more diverse composition rich in Bacteroidetes and Firmicutes. In the experiment where infant microbiome was used, the phylogenetic composition of the transplanted bacterial population converged toward that of the human inoculum. A majority of sequences belonged to a relatively small number of operational taxonomic units, whereas at the other end of the abundance spectrum, a large number of rare and transient OTUs were detected. Analysis of fecal and colonic microbiomes originating from the same animal indicate that feces closely replicate the colonic microbiome. We conclude that the pig intestine can be colonized with human fecal microbiomes to generate a realistic model of the human GI tract.}, }
@article {pmid23547144, year = {2013}, author = {Mori, K and Yamanishi, H and Ikeda, Y and Kumagi, T and Hiasa, Y and Matsuura, B and Abe, M and Onji, M}, title = {Oral administration of carbonic anhydrase I ameliorates murine experimental colitis induced by Foxp3-CD4+CD25- T cells.}, journal = {Journal of leukocyte biology}, volume = {93}, number = {6}, pages = {963-972}, doi = {10.1189/jlb.1212612}, pmid = {23547144}, issn = {1938-3673}, mesh = {Administration, Oral ; Animals ; CD4-Positive T-Lymphocytes/*immunology/transplantation ; Carbonic Anhydrase I/*administration &amp; dosage/immunology ; Colitis/*immunology/prevention &amp; control ; Desensitization, Immunologic/*methods ; Disease Models, Animal ; Female ; Flow Cytometry ; Immune Tolerance/immunology ; Immunohistochemistry ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Real-Time Polymerase Chain Reaction ; T-Lymphocyte Subsets/*immunology/transplantation ; }, abstract = {IBDs are thought to involve uncontrolled innate and adaptive immunity against intestinal self-antigens and bacterial antigens. Mouse CA I is a major cecal bacterial antigen in fecal extracts and is implicated in the pathogenesis of IBD. We show here that oral tolerization to CA I induced antigen-specific protection from intestinal inflammation in a murine model. Oral administration of CA I but not irrelevant antigen (KLH) ameliorated CD4(+)CD25(-) T cell transfer murine colitis and DSS-induced murine colitis. Next, we investigated the mechanisms involved in the therapeutic effects of oral administration, such as induction of ALDH1a2, transcription factors, cytokines, CD103(+)CD11c(+) DCs, and generation of Tregs. Oral administration of CA I induced ALDH1a2 mRNA expression in the MLN and colon. When compared with PBS-treated mice, CA I-treated mice had higher Foxp3(+)CD4(+)CD25(+) Treg and CD103(+)CD11c(+) DC numbers in the MLN and colon; had higher TGF-β production in the MLN and colon; had lower RORγt mRNA expression in the MLN and colon; and had lower IL-17 mRNA expression and production in the MLN. These results demonstrate that oral administration of CA I induced antigen-specific immune tolerance by generating Foxp3(+)CD4(+)CD25(+) Tregs and inhibiting Th17 cells in a murine colitis model, thus suggesting that oral tolerization with CA I is an effective therapeutic strategy for IBD regulation.}, }
@article {pmid23542823, year = {2013}, author = {Kunde, S and Pham, A and Bonczyk, S and Crumb, T and Duba, M and Conrad, H and Cloney, D and Kugathasan, S}, title = {Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {56}, number = {6}, pages = {597-601}, doi = {10.1097/MPG.0b013e318292fa0d}, pmid = {23542823}, issn = {1536-4801}, mesh = {Administration, Rectal ; Adolescent ; Adult ; *Biological Therapy/adverse effects ; Child ; Colitis, Ulcerative/microbiology/physiopathology/*therapy ; Donor Selection ; Dysbiosis/etiology/*prevention &amp; control ; Family ; Feasibility Studies ; Feces/*microbiology ; Female ; Follow-Up Studies ; Hospitals, Pediatric ; Humans ; Male ; Michigan ; Outpatient Clinics, Hospital ; Pilot Projects ; Remission Induction ; Severity of Illness Index ; *Therapies, Investigational/adverse effects ; Young Adult ; }, abstract = {BACKGROUND AND OBJECTIVE: Colonic dysbiosis contributes to the development of colonic inflammation in ulcerative colitis (UC). Fecal microbial transplantation (FMT) is being proposed as a novel treatment for UC because it can eliminate dysbiosis; however, no prospective data exist. We initiated a pilot study to evaluate feasibility and safety of FMT in children with UC.<br><br>METHODS: Ten children, 7 to 21 years of age, with mild-to-moderate UC (pediatric UC activity index [PUCAI] between 15 and 65) received freshly prepared fecal enemas daily for 5 days. Data on tolerability, adverse events, and disease activity were collected during FMT and weekly for 4 weeks after FMT. Clinical response was defined as decrease in PUCAI by >15, and decrease in PUCAI to <10 was considered clinical remission.<br><br>RESULTS: No serious adverse events were noted. Mild (cramping, fullness, flatulence, bloating, diarrhea, and blood in stool) to moderate (fever) adverse events were self-limiting. One subject could not retain fecal enemas. Average tolerated enema volume by remaining 9 subjects was 165 mL/day. After FMT, 7 of the 9 (78%) subjects showed clinical response within 1 week, 6 of the 9 (67%) subjects maintained clinical response at 1 month, and 3 of the 9 (33%) subjects achieved clinical remission at 1 week after FMT. Median PUCAI significantly improved after FMT (P = 0.03) compared with the baseline.<br><br>CONCLUSIONS: Fecal enemas were feasible and tolerated by children with UC. Adverse events were acceptable, self-limiting, and manageable by subjects. FMT indicated efficacy in the treatment of UC.}, }
@article {pmid23542332, year = {2013}, author = {Dupont, HL}, title = {Diagnosis and management of Clostridium difficile infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {11}, number = {10}, pages = {1216-23; quiz e73}, doi = {10.1016/j.cgh.2013.03.016}, pmid = {23542332}, issn = {1542-7714}, mesh = {Administration, Oral ; Aminoglycosides/therapeutic use ; Anti-Infective Agents/therapeutic use ; Biological Therapy/methods ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*diagnosis/*drug therapy/microbiology ; Colectomy ; False Positive Reactions ; Fidaxomicin ; Humans ; Immunotherapy/methods ; Metronidazole/therapeutic use ; Molecular Diagnostic Techniques/methods ; Vancomycin/therapeutic use ; }, abstract = {Clostridium difficile infection (CDI) is increasing in frequency and severity in and out of the hospital, with a high probability of recurrence after treatment. The recent literature on CDI was reviewed using PubMed to include recent publications dealing with diagnosis and therapy. Real-time polymerase chain reaction is a sensitive and useful diagnostic test for CDI but there are growing concerns of false-positive test results if the rate of CDI is low in the patient population providing samples and/or if the population being studied commonly includes people with C difficile colonization. Recommended therapy of CDI includes oral metronidazole for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases, each given for 10 days. Colectomy is being performed more frequently in patients with fulminant CDI. For treatment of first recurrences the drug used in the first bout can be used again and for second recurrences longer courses of vancomycin often are given in a tapered dose or intermittently to allow gut flora reconstitution, or other treatments including fidaxomicin may be used. Bacteriotherapy with fecal transplantation is playing an increasing role in therapy of recurrent cases. Metagenomic studies of patients with CDI during successful therapy are needed to determine how best to protect the flora from assaults from antibacterial drugs and to develop optimal therapeutic approaches. Immunotherapy and immunoprophylaxis offer opportunities to prevent CDI, to speed up recovery from CDI, and to eliminate recurrent infection. Humanized monoclonal antitoxin antibodies and active immunization with vaccines against C difficile or its toxins are both in development and appear to be of potential value.}, }
@article {pmid23538355, year = {2013}, author = {Gorsane, I and Aloui, S and Letaif, A and Hadhri, R and Haouala, F and Frih, A and Dhia, NB and Elmay, M and Skhiri, H}, title = {Cytomegalovirus ischemic colitis and transverse myelitis in a renal transplant recipient.}, journal = {Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia}, volume = {24}, number = {2}, pages = {309-314}, doi = {10.4103/1319-2442.109588}, pmid = {23538355}, issn = {1319-2442}, mesh = {Abdominal Pain/etiology ; Antiviral Agents/therapeutic use ; Biopsy ; Colitis, Ischemic/diagnosis/drug therapy/*etiology/virology ; Colonoscopy ; Cytomegalovirus/genetics ; Cytomegalovirus Infections/diagnosis/drug therapy/*etiology/virology ; DNA, Viral/analysis ; Ganciclovir/therapeutic use ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Immunologic Factors/therapeutic use ; Kidney Transplantation/*adverse effects ; Magnetic Resonance Imaging ; Male ; Melena/etiology ; Middle Aged ; Myelitis, Transverse/diagnosis/drug therapy/*etiology/virology ; Polymerase Chain Reaction ; Predictive Value of Tests ; Treatment Outcome ; }, abstract = {We report a rare case of cytomegalovirus (CMV)-associated ischemic colitis and transverse myelitis (TM) occurring precociously after renal transplantation. A 57-year-old male was transplanted with a cadaveric kidney on 5 June 2009. The patient was CMV seropositive and the donor was seronegative. Transplantation was followed shortly by TM, which resulted in paraplegia. The results of magnetic resonance imaging of the spinal cord showed abnormalities. Twenty days after transplantation, he developed abdominal pain with melena and was diagnosed as having CMV-associated ischemic colitis confirmed by colonoscopy and biopsy. Serological data and identification of the viral genome by polymerase chain reaction were confirmatory for CMV. Treatment consisted of intravenous ganciclovir, followed by polyvalent immunoglobulin. The outcome was favorable. Symptomatic CMV infection is relatively common among the renal transplant population. Early colonoscopy is beneficial for making a quick diagnosis and therefore helps to institute a prompt management of CMV colitis. Myelitis is less common in transplant recipients and diagnosis, therefore, was more difficult.}, }
@article {pmid23530761, year = {2013}, author = {Toh, MC and Goodyear, M and Daigneault, M and Allen-Vercoe, E and Van Raay, TJ}, title = {Colonizing the embryonic zebrafish gut with anaerobic bacteria derived from the human gastrointestinal tract.}, journal = {Zebrafish}, volume = {10}, number = {2}, pages = {194-198}, doi = {10.1089/zeb.2012.0814}, pmid = {23530761}, issn = {1557-8542}, mesh = {Animals ; Bacteria, Anaerobic/genetics/growth &amp; development/*isolation &amp; purification/metabolism ; Eubacterium/genetics/growth &amp; development/isolation &amp; purification/metabolism ; Feces/microbiology ; Gastrointestinal Tract/*microbiology ; *Germ-Free Life ; Humans ; Immersion ; Lactobacillus/genetics/growth &amp; development/isolation &amp; purification/metabolism ; Larva/growth &amp; development/microbiology ; Microinjections ; *Models, Animal ; Zebrafish/growth &amp; development/*microbiology ; }, abstract = {The zebrafish has become increasingly popular for microbiological research. It has been used as an infection model for a variety of pathogens, and is also emerging as a tool for studying interactions between a host and its resident microbial communities. The mouse microbiota has been transplanted into the zebrafish gut, but to our knowledge, there has been no attempt to introduce a bacterial community derived from the human gut. We explored two methods for colonizing the developing gut of 5-day-old germ-free zebrafish larvae with a defined anaerobic microbial community derived from a single human fecal sample. Both environmental exposure (static immersion) and direct microinjection into the gut resulted in the establishment of two species-Lactobacillus paracasei and Eubacterium limosum-from a community of 30 strains consisting of 22 anaerobic species. Of particular interest is E. limosum, which, as a strict anaerobe, represents a group of bacteria which until now have not been shown to colonize the developing zebrafish gut. Our success here indicates that further investigation of zebrafish as a tool for studying human gut microbial communities is warranted.}, }
@article {pmid23524964, year = {2013}, author = {Martel, C and Li, W and Fulp, B and Platt, AM and Gautier, EL and Westerterp, M and Bittman, R and Tall, AR and Chen, SH and Thomas, MJ and Kreisel, D and Swartz, MA and Sorci-Thomas, MG and Randolph, GJ}, title = {Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice.}, journal = {The Journal of clinical investigation}, volume = {123}, number = {4}, pages = {1571-1579}, pmid = {23524964}, issn = {1558-8238}, support = {R01 HL-096539/HL/NHLBI NIH HHS/United States ; S10 RR027940/RR/NCRR NIH HHS/United States ; P30 DK056341/DK/NIDDK NIH HHS/United States ; R01 HL064163/HL/NHLBI NIH HHS/United States ; P30 CA091842/CA/NCI NIH HHS/United States ; P30 DK020579/DK/NIDDK NIH HHS/United States ; 1S10RR027940MS/RR/NCRR NIH HHS/United States ; UL1RR024992/RR/NCRR NIH HHS/United States ; UL1 RR024992/RR/NCRR NIH HHS/United States ; P30 CA91842/CA/NCI NIH HHS/United States ; R01 CA109322/CA/NCI NIH HHS/United States ; P30 CA012197/CA/NCI NIH HHS/United States ; R01 HL-64163/HL/NHLBI NIH HHS/United States ; 5P30CA12197/CA/NCI NIH HHS/United States ; R01 HL096539/HL/NHLBI NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Aorta, Thoracic/metabolism/transplantation ; Atherosclerosis/metabolism/pathology ; Capillary Permeability ; Carcinoma, Lewis Lung/blood supply/metabolism ; Cholesterol/*blood/metabolism ; Gene Expression ; Kinetics ; Lymphatic Vessels/*metabolism ; Macrophages/*metabolism ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Transgenic ; Sinus of Valsalva/metabolism ; Skin/metabolism ; Vascular Endothelial Growth Factor Receptor-3/antagonists &amp; inhibitors/genetics/metabolism ; }, abstract = {Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin--1 surgical and the other genetic--to quantitatively track RCT following injection of [3H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.}, }
@article {pmid23523165, year = {2013}, author = {Kaoutzanis, C and Pannucci, CJ and Sherick, D}, title = {Use of gracilis muscle as a "walking" flap for repair of a rectovaginal fistula.}, journal = {Journal of plastic, reconstructive &amp; aesthetic surgery : JPRAS}, volume = {66}, number = {7}, pages = {e197-200}, doi = {10.1016/j.bjps.2013.03.002}, pmid = {23523165}, issn = {1878-0539}, mesh = {Female ; Graft Rejection/surgery ; Hemorrhoidectomy/*adverse effects/methods ; Hemorrhoids/surgery ; Humans ; Ileostomy/methods ; Middle Aged ; Muscle, Skeletal/surgery/transplantation ; Postoperative Complications/diagnosis/surgery ; Quality of Life ; Plastic Surgery Procedures/adverse effects/*methods ; Rectovaginal Fistula/*etiology/physiopathology/*surgery ; Reoperation/methods ; Risk Assessment ; Surgical Flaps/*blood supply ; Thigh/surgery ; Treatment Outcome ; }, abstract = {Rectovaginal fistula is a rare but debilitating complication of a variety of pelvic operations. Management remains challenging with high incidence of failure. The majority of patients eventually require surgical intervention. Several surgical procedures have been described including local repair, muscle transposition, or laparotomy. Among the muscles used for rectovaginal fistula repair, the gracilis muscle interposition flap is an excellent option. However, in a small percentage of cases it fails, and alternative techniques should be entertained. We describe the case of a 50-year-old female who underwent stapled hemorrhoidopexy that was complicated by a 30 mm rectovaginal fistula, and required fecal diversion. Four months later, gracilis muscle interposition flap was performed but failed. The right gracilis flap was then re-used successfully as a "walking" flap. At three months the patient underwent closure of the temporary loop ileostomy, and continues to do well with no evidence of rectovaginal fistula recurrence one year later. To our knowledge, this is the first report of the use of a gracilis muscle as a "walking" flap for repair of a rectovaginal fistula, and should be considered as an alternative appropriate treatment for persistent rectovaginal fistulas after failure of initial gracilis muscle interposition flap.}, }
@article {pmid23511459, year = {2013}, author = {Kassam, Z and Lee, CH and Yuan, Y and Hunt, RH}, title = {Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {4}, pages = {500-508}, doi = {10.1038/ajg.2013.59}, pmid = {23511459}, issn = {1572-0241}, mesh = {Biological Therapy/*methods ; Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Metagenome/*physiology ; Treatment Outcome ; }, abstract = {OBJECTIVES: The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI.<br><br>METHODS: An electronic search was conducted using MEDLINE (1946-March 2012), EMBASE (1974-March 2012) and Cochrane Central Register of Controlled Trials (2012). The search strategy was not limited by language. Abstract data were excluded and only completed studies that underwent the full, rigorous peer-review process were included. Studies that used FMT via any delivery modality for laboratory or endoscopically proven CDI with clinical resolution as primary outcome were included. A sample size of 10 or more patients was a further criterion. Elements of the Centre for Reviews and Dissemination checklist and the National Institute of Clinical Excellence quality assessment for case series checklist were employed to determine study quality. Eligibility assessment and data extraction were performed by two independent researchers. Both unweighted pooled resolution rates (UPR) and weighted pooled resolution rates (WPR) were calculated with corresponding 95% confidence intervals (CI) for overall studies, as well as predefined subgroups.<br><br>RESULTS: Eleven studies with a total of 273 CDI patients treated with FMT were identified; no RCTs were found as none have been published. Two-hundred and forty-five out of 273 patients experienced clinical resolution (UPR 89.7%; WPR 89.1% (95% CI 84 to 93%)). There was no statistically significant heterogeneity between studies (Cochran Q test P=0.13, I(2)=33.7%). A priori subgroup analysis suggested that lower gastrointestinal FMT delivery (UPR 91.4%; WPR 91.2% (95% CI 86 to 95%)) led to a trend towards higher clinical resolution rates than the upper gastrointestinal route (UPR 82.3%; WPR 80.6% (95% CI 69-90%)) (proportion difference of WPR was 10.6% (95% CI -0.6 to 22%)). No difference in clinical outcomes was detected between anonymous vs. patient selected donors. There were no reported adverse events associated with FMT and follow-up was variable from weeks to years.<br><br>CONCLUSIONS: FMT holds considerable promise as a therapy for recurrent CDI but well-designed, RCTs and long-term follow-up registries are still required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated.}, }
@article {pmid23504024, year = {2013}, author = {Lu, H and He, J and Wu, Z and Xu, W and Zhang, H and Ye, P and Yang, J and Zhen, S and Li, L}, title = {Assessment of microbiome variation during the perioperative period in liver transplant patients: a retrospective analysis.}, journal = {Microbial ecology}, volume = {65}, number = {3}, pages = {781-791}, pmid = {23504024}, issn = {1432-184X}, mesh = {Adult ; Bacteria/classification/genetics/*isolation &amp; purification ; Cross Infection/microbiology/*prevention &amp; control ; Feces/microbiology ; Humans ; Intestines/*microbiology ; *Liver Transplantation ; Male ; *Metagenome ; Perioperative Period ; Phylogeny ; Postoperative Complications/microbiology/*prevention &amp; control ; Retrospective Studies ; }, abstract = {Understanding the composition of the microbial populations in the intestines of liver transplant patients is important to preventing postoperative infection. We investigated the relationship between the risk of postoperative infection and variation in the predominant fecal microbial composition during the perioperative period. We prospectively analyzed the predominant intestinal microbiome of five asymptomatic adult carriers of hepatitis B virus (as controls without any antibiotics) at four weekly follow-up visits and 12 patients before operation and at three weekly postoperative follow-up visits within the first month. Analysis was by denaturing gradient gel electrophoresis (DGGE) and sequencing with digital processing of DGGE profiles using BioNumerics software. Our results showed that the predominant intestinal microbial diversity decreased substantially in eight patients during the perioperative period. Among these, five patients experienced infection with a postoperative hospital stay of more than 30 days. The rest of the four patients who experienced shorter postoperative hospital stays showed only slight variation in predominant intestinal bacterial composition and temporal stability similar to asymptomatic controls. Postoperative fecal DGGE profiles showed mostly bands assigned to Bacteroides and Firmicutes. We conclude that an empiric prophylaxis strategy that destructs gut microecological balance will not be effective in reducing the risk of postoperative infection. Instead, the destruction of intestinal microbiota might result in the appearance of opportunistic pathogens such as Bifidobacterium dentium which rarely appears in the intestinal DGGE profiles of normal humans. Cognizance of the variation of intestinal microbial profiles during the perioperative period is a critical aspect of caring for liver transplant recipients.}, }
@article {pmid23497650, year = {2013}, author = {Bested, AC and Logan, AC and Selhub, EM}, title = {Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: part III - convergence toward clinical trials.}, journal = {Gut pathogens}, volume = {5}, number = {1}, pages = {4}, pmid = {23497650}, issn = {1757-4749}, abstract = {Rapid scientific and technological advances have allowed for a more detailed understanding of the relevance of intestinal microbiota, and the entire body-wide microbiome, to human health and well-being. Rodent studies have provided suggestive evidence that probiotics (e.g. lactobacillus and bifidobacteria) can influence behavior. More importantly, emerging clinical studies indicate that the administration of beneficial microbes, via supplementation and/or fecal microbial transplant (FMT), can influence end-points related to mood state (glycemic control, oxidative status, uremic toxins), brain function (functional magnetic resonance imaging fMRI), and mental outlook (depression, anxiety). However, despite the advances in the area of gastro-biological psychiatry, it becomes clear that there remains an urgent need to explore the value of beneficial microbes in controlled clinical investigations. With the history explored in this series, it is fair to ask if we are now on the cusp of major clinical breakthroughs, or are we merely in the quicksand of Autointoxication II?}, }
@article {pmid23488112, year = {2013}, author = {McKinney, M}, title = {Despite 'eww' factor... fecal transplants gain ground against C. diff.}, journal = {Modern healthcare}, volume = {43}, number = {4}, pages = {12-13}, pmid = {23488112}, issn = {0160-7480}, mesh = {Biological Therapy/economics/*methods ; *Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Feces/*microbiology ; Humans ; Probiotics/*administration &amp; dosage ; Randomized Controlled Trials as Topic ; Recurrence ; United States ; }, }
@article {pmid23478618, year = {2013}, author = {Ruttenstock, EM and Zani, A and Huber-Zeyringer, A and Höllwarth, ME}, title = {Pre- and postoperative rectal manometric assessment of patients with anorectal malformations: should we preserve the fistula?.}, journal = {Diseases of the colon and rectum}, volume = {56}, number = {4}, pages = {499-504}, doi = {10.1097/DCR.0b013e31826e4a38}, pmid = {23478618}, issn = {1530-0358}, mesh = {Anal Canal/*abnormalities/*surgery ; Child, Preschool ; Defecation ; Digestive System Surgical Procedures ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Manometry ; Postoperative Care ; Preoperative Care ; Prospective Studies ; Rectal Fistula/*surgery ; Rectum/*abnormalities/*surgery ; Reflex ; }, abstract = {BACKGROUND: Surgical correction of congenital anorectal malformations could be complicated by fecal incontinence. Some authors believe that preservation of the fistula is associated with improved outcome. Rectal manometry is a well-established method to evaluate postoperative functional outcome in these patients and can demonstrate successful transplantation of the fistula.<br><br>OBJECTIVE: Herein, we report the results of our series of patients with anorectal malformations and an externally accessible fistula, who underwent pre- and postoperative rectal manometry studies.<br><br>DESIGN: This is a prospective cohort study.<br><br>SETTINGS: This study was conducted at a tertiary neonatal and pediatric surgical center.<br><br>PATIENTS: Patients with anorectal malformations, who underwent preoperative rectal manometry of the fistula and postoperative rectal manometry of the neoanus between January 2002 and December 2011 were included.<br><br>MAIN OUTCOME MEASURES: Pre- and postoperative rectal manometry results were compared by using paired t test or contingency tables (p values <0.05).<br><br>RESULTS: Twelve female patients with rectoperineal (n = 7, 58%) or rectovestibular (n = 5, 42%) fistula were treated by anterior sagittal anorectoplasty or minimal posterior sagittal anorectoplasty. Complete transposition of the fistula was achieved in all patients. Normal presence of rectoanal inhibitory reflex was demonstrated in all pre- and postoperative rectal manometry studies. There were no differences between pre- and postoperative rectal manometry in the length of the high-pressure zone (2.3 &#xb1; 0.6 cm vs 2.5 &#xb1; 0.8 cm (p = 0.5)) and resting pressure (59.4 &#xb1; 18.2 mm Hg vs 62.1 &#xb1; 19.2 mm Hg (p = 0.62)). At a median follow-up of 665 days (range, 290-1165 days), all patients have voluntary bowel movements, with no incontinence or soiling.<br><br>LIMITATIONS: This study is limited by its small sample size and by single-institution bias.<br><br>CONCLUSION: Preoperative rectal manometry of rectoperineal or rectovestibular fistula showed the presence of functional anal structures within the fistula in all patients. We speculate that fistula-preserving surgery in patients with anorectal malformations is associated with improved bowel function outcome.}, }
@article {pmid23468820, year = {2013}, author = {Kleger, A and Schnell, J and Essig, A and Wagner, M and Bommer, M and Seufferlein, T and Härter, G}, title = {Fecal transplant in refractory Clostridium difficile colitis.}, journal = {Deutsches Arzteblatt international}, volume = {110}, number = {7}, pages = {108-115}, pmid = {23468820}, issn = {1866-0452}, mesh = {Aged ; Chronic Disease ; *Clostridioides difficile ; Colitis/*microbiology/*therapy ; Enterocolitis, Pseudomembranous/*microbiology/*therapy ; Feces/*microbiology ; Female ; Humans ; Probiotics/*therapeutic use ; Treatment Failure ; Treatment Outcome ; }, abstract = {BACKGROUND: Clostridium difficile infections are becoming more common, more severe, and more likely to recur. Conventional treatment with antibiotics often fails to eradicate the infection; even when it succeeds, recurrent infection is common. Complementary treatment with probiotic agents to reconstitute the physiological intestinal flora does not yield any consistent benefit. In recent years, fecal transplantation has been used in the English-speaking countries with cure rates of about 87%, but the available evidence is limited to large case series. No randomized controlled trials have been performed. We present the case of a 73-year-old woman with intractable, recurrent enterocolitis due to Clostridium difficile who was successfully treated with fecal transplantation via colonoscopy.<br><br>CASE DESCRIPTION: Upon the completion of antibiotic treatment for a second recurrence of enterocolitis, stool in liquid suspension was introduced into the patient's colon through a colonoscope. Prior testing had shown the stool donor to be free of acute infection or stool pathogens. The patient was given loperamide to prolong contact of the stool transplant with the colonic mucosa. She was also treated with Saccharomyces cerevisiae for four weeks.<br><br>COURSE: There was no clinical or microbiological evidence of a further recurrence of enterocolitis for 6 months after transplantation. Stool transplantation had no adverse effects.<br><br>CONCLUSION: This patient had a lasting remission of enterocolitis due to Clostridium difficile after the treatment described above. Fecal transplantation seems to be a safe and highly effective treatment for recurrent Clostridium difficile infection. It is unclear whether the administration of Saccharomyces cerevisiae confers any additional benefit.}, }
@article {pmid23435617, year = {2013}, author = {Kneist, W and Kauff, DW and Naumann, G and Lang, H}, title = {Resection rectopexy--laparoscopic neuromapping reveals neurogenic pathways to the lower segment of the rectum: preliminary results.}, journal = {Langenbeck's archives of surgery}, volume = {398}, number = {4}, pages = {565-570}, pmid = {23435617}, issn = {1435-2451}, mesh = {Adult ; Aged ; Anal Canal/innervation ; Cystocele/*surgery ; Electric Stimulation ; Electrodes ; Electromyography ; Fecal Incontinence/physiopathology/prevention &amp; control ; Female ; Humans ; Intraoperative Complications/physiopathology/*prevention &amp; control ; Laparoscopy/*methods ; Middle Aged ; Monitoring, Intraoperative ; Pelvic Floor/innervation/surgery ; Postoperative Complications/physiopathology/prevention &amp; control ; Rectal Prolapse/*surgery ; Rectocele/*surgery ; Rectum/*innervation/*surgery ; Splanchnic Nerves/injuries/*physiopathology ; *Suburethral Slings ; Urinary Bladder/innervation ; Urinary Incontinence/physiopathology/prevention &amp; control ; Uterine Prolapse/*surgery ; }, abstract = {PURPOSE: Nerve sparing in functional pelvic floor surgery is strongly recommended as intraoperative damage to the autonomic nerves may predispose to persistent or worsened anorectal and urogenital function. The aim of this study was to investigate the intraoperative neural topography above the pelvic floor in patients undergoing laparoscopic resection rectopexy in combination with electrophysiologic neuromapping.<br><br>METHODS: Ten consecutive female patients underwent laparoscopic resection rectopexy for rectal prolapse. Intraoperative identification of pelvic autonomic nerves was carried out with a novel intraoperative neuromonitoring system based on electric stimulation under simultaneous electromyography of the internal anal sphincter and manometry of the bladder. Neuromonitoring results were compared to patients' preoperative anorectal and urogenital function and their functional results at the 3-month follow-up.<br><br>RESULTS: Laparoscopy in combination with electrophysiologic neuromapping revealed neurogenic pathways to the lower segment of the rectum during surgical mobilization. In all procedures, intraoperative neuromonitoring finally confirmed functional nerve integrity to the internal anal sphincter and the bladder. Patients with preoperatively diagnosed fecal incontinence were continent at the 3-month follow-up. The Wexner score improved in median from preoperative 4 (range 1-18) to 1 (range 0-3) at follow-up (p&#x2009;=&#x2009;0.012). Cleveland Clinical Constipation Score improved in median from 10 (range 5-17) to 3 (range 1-7; p&#x2009;=&#x2009;0.005). In none of the investigated patients a new onset of urinary dysfunction did occur. No change in sexual function was observed.<br><br>CONCLUSIONS: Laparoscopy in combination with electrophysiologic neuromapping during nerve-sparing resection rectopexy identified and preserved neurogenic pathways heading to the lower segment of the rectum above the level of the pelvic floor.}, }
@article {pmid23434948, year = {2013}, author = {Hell, M and Bernhofer, C and Stalzer, P and Kern, JM and Claassen, E}, title = {Probiotics in Clostridium difficile infection: reviewing the need for a multistrain probiotic.}, journal = {Beneficial microbes}, volume = {4}, number = {1}, pages = {39-51}, doi = {10.3920/BM2012.0049}, pmid = {23434948}, issn = {1876-2891}, mesh = {Biological Products/*administration &amp; dosage ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/*microbiology/*therapy ; Humans ; Probiotics/*administration &amp; dosage ; }, abstract = {In the past two years an enormous amount of molecular, genetic, metabolomic and mechanistic data on the host-bacterium interaction, a healthy gut microbiota and a possible role for probiotics in Clostridium difficile infection (CDI) has been accumulated. Also, new hypervirulent strains of C. difficile have emerged. Yet, clinical trials in CDI have been less promising than in antibiotic associated diarrhoea in general, with more meta-analysis than primary papers on CDI-clinical-trials. The fact that C. difficile is a spore former, producing at least three different toxins has not yet been incorporated in the rational design of probiotics for (recurrent) CDI. Here we postulate that the plethora of effects of C. difficile and the vast amount of data on the role of commensal gut residents and probiotics point towards a multistrain mixture of probiotics to reduce CDI, but also to limit (nosocomial) transmission and/or endogenous reinfection. On the basis of a retrospective chart review of a series of ten CDI patients where recurrence was expected, all patients on adjunctive probiotic therapy with multistrain cocktail (Ecologic®AAD/OMNiBiOTiC® 10) showed complete clinical resolution. This result, and recent success in faecal transplants in CDI treatment, are supportive for the rational design of multistrain probiotics for CDI.}, }
@article {pmid23427910, year = {2013}, author = {Zucca, M and Scutera, S and Savoia, D}, title = {Novel avenues for Clostridium difficile infection drug discovery.}, journal = {Expert opinion on drug discovery}, volume = {8}, number = {4}, pages = {459-477}, doi = {10.1517/17460441.2013.770466}, pmid = {23427910}, issn = {1746-045X}, mesh = {Anti-Infective Agents/*therapeutic use ; Bacteriophages/growth &amp; development ; Clostridioides difficile/*drug effects ; Clostridium Infections/*drug therapy ; Drug Discovery/*methods ; Feces/microbiology ; Humans ; Metagenome/drug effects ; }, abstract = {INTRODUCTION: Clostridium difficile is the etiologic agent of nosocomial and community-acquired diarrhea associated with exposure to antibiotics that disrupt the normal colonic flora. As antibacterials currently used for primary C. difficile infections favor recurrences, new agents able to neutralize the bacterium without affecting the gut microbiota are badly needed.<br><br>AREAS COVERED: This article investigates the most promising strategies aimed at developing therapies with minimal or no effect on intestinal flora. These therapies include new narrow-spectrum antibiotics and antimicrobial peptides, bacteriophages and phage lysins, virulence-targeting factors such as riboswitch ligands and quorum sensing-interfering factors. It also reviews bacteriotherapy based on probiotics, fecal transplants, and toxin-targeting molecules.<br><br>EXPERT OPINION: Beyond the development of new antibiotics, virulence-targeting factors or phage cocktails seem promising strategies, which could replace antibiotics avoiding the emergence of resistant strains and the onset of C. difficile infection (CDI). Until broad-spectrum antimicrobials will be in use, C. difficile-specific lytic phages could help to prevent CDI by eliminating C. difficile in patients and in the hospital staff, and for the prevention and treatment of recurrences. Phage therapy is not currently available in Western countries, but, in our opinion, it should have a new chance. Fecal therapy is emerging as a very effective and readily available treatment for recurrences. The shift is from a standardized, drug-based antibacterial therapy toward the forthcoming less expensive and nonpatentable procedures of a more personalized medicine. This will imply profound changes affecting both patient-physician interactions and the current profit-oriented approach to the pharmacologic therapy of infections.}, }
@article {pmid23422477, year = {2013}, author = {Jacobsen, KR and Jørgensen, P and Pipper, CB and Steffensen, AM and Hau, J and Abelson, KS}, title = {The utility of fecal corticosterone metabolites and animal welfare assessment protocols as predictive parameters of tumor development and animal welfare in a murine xenograft model.}, journal = {In vivo (Athens, Greece)}, volume = {27}, number = {2}, pages = {189-196}, pmid = {23422477}, issn = {1791-7549}, mesh = {Animals ; *Behavior, Animal ; Body Weight ; Corticosterone/analysis/*metabolism ; Drinking ; Eating ; Feces/*chemistry ; Male ; Mice ; Mice, SCID ; Neoplasm Transplantation/pathology/psychology ; *Neoplasms, Experimental/metabolism/pathology/psychology ; *Prostatic Neoplasms/metabolism/pathology/psychology ; Stress, Physiological/physiology ; *Xenograft Model Antitumor Assays ; }, abstract = {The aim of the present study was to evaluate the utility of various non-invasive parameters for the prediction of tumor development and animal welfare in a murine xenograft model in male C.B-17 SCID (C.B-Igh-1(b)/IcrTac-Prkdc(scid)) mice. The study showed that body weight, food and water consumption, and an animal welfare assessment (AWA) protocol revealed marked differences between control and cancer lines as the size of the tumor increased. However, only the AWA protocol was effective in predicting the tumor size and the level of fecal corticosterone metabolites (FCM). FCM levels were, however, negatively-correlated to the AWA score, and the tumor size, both when evaluated on a given day and when accumulated over the entire period. In conclusion, the present study demonstrated that body weight and food and water consumption were negatively-affected as tumor developed but only the animal welfare protocol could be used to predict tumor size.}, }
@article {pmid23378145, year = {2013}, author = {Yeoh, N and Burton, JP and Suppiah, P and Reid, G and Stebbings, S}, title = {The role of the microbiome in rheumatic diseases.}, journal = {Current rheumatology reports}, volume = {15}, number = {3}, pages = {314}, pmid = {23378145}, issn = {1534-6307}, mesh = {Anti-Bacterial Agents/pharmacology ; Diet ; Gastrointestinal Tract/immunology/microbiology ; Humans ; Immune Tolerance ; Metagenome/drug effects/*physiology ; Mouth/microbiology ; Obesity ; Probiotics/therapeutic use ; Rheumatic Diseases/drug therapy/genetics/immunology/*microbiology ; }, abstract = {There is a growing understanding of the mechanisms by which the influence of the microbiota projects beyond sites of primary mucosal occupation to other human body systems. Bacteria present in the intestinal tract exert a profound effect on the host immune system, both locally and at distant sites. The oral cavity has its own characteristic microbiota, which concentrates in periodontal tissues and is in close association with a permeable epithelium. In this review we examine evidence which supports a role for the microbiome in the aetiology of rheumatic disease. We also discuss how changes in the composition of the microbiota, particularly within the gastrointestinal tract, may be affected by genetics, diet, and use of antimicrobial agents. Evidence is presented to support the theory that an altered microbiota is a factor in the initiation and perpetuation of inflammatory diseases, including rheumatoid arthritis (RA), spondyloarthritis (SpA), and inflammatory bowel disease (IBD). Mechanisms through which the microbiota may be involved in the pathogenesis of these diseases include altered epithelial and mucosal permeability, loss of immune tolerance to components of the indigenous microbiota, and trafficking of both activated immune cells and antigenic material to the joints. The potential to manipulate the microbiome, by application of probiotics and faecal microbial transplant (FMT), is now being investigated. Both approaches are in their infancy with regard to management of rheumatic disease but their potential is worthy of consideration, given the need for novel therapeutic approaches, and the emerging recognition of the importance of microbial interactions with human hosts.}, }
@article {pmid23376915, year = {2013}, author = {Agito, MD and Atreja, A and Rizk, MK}, title = {Fecal microbiota transplantation for recurrent C difficile infection: ready for prime time?.}, journal = {Cleveland Clinic journal of medicine}, volume = {80}, number = {2}, pages = {101-108}, doi = {10.3949/ccjm.80a.12110}, pmid = {23376915}, issn = {1939-2869}, mesh = {Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; *Microbiota ; Recurrence ; *Transplantation ; Treatment Outcome ; }, abstract = {Recurrent Clostridium difficile infection has been a major challenge for patients and clinicians. Recurrence of infection after treatment with standard antibiotics is becoming more common with the emergence of more-resistant strains of C difficile. Fecal microbiota transplantation is an alternative treatment for recurrent C difficile infection, but it is not yet widely used.}, }
@article {pmid23376908, year = {2013}, author = {Mandell, BF}, title = {A weirder than weird story, and yet..}, journal = {Cleveland Clinic journal of medicine}, volume = {80}, number = {2}, pages = {73}, doi = {10.3949/ccjm.80b.02013}, pmid = {23376908}, issn = {1939-2869}, mesh = {Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; *Microbiota ; *Transplantation ; }, }
@article {pmid23363771, year = {2013}, author = {Smith, MI and Yatsunenko, T and Manary, MJ and Trehan, I and Mkakosya, R and Cheng, J and Kau, AL and Rich, SS and Concannon, P and Mychaleckyj, JC and Liu, J and Houpt, E and Li, JV and Holmes, E and Nicholson, J and Knights, D and Ursell, LK and Knight, R and Gordon, JI}, title = {Gut microbiomes of Malawian twin pairs discordant for kwashiorkor.}, journal = {Science (New York, N.Y.)}, volume = {339}, number = {6119}, pages = {548-554}, pmid = {23363771}, issn = {1095-9203}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK030292/DK/NIDDK NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; T32-HD049338/HD/NICHD NIH HHS/United States ; T32 HD049338/HD/NICHD NIH HHS/United States ; DK30292/DK/NIDDK NIH HHS/United States ; DK078669/DK/NIDDK NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; F32 DK091044/DK/NIDDK NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; T35 DK074375/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acids/metabolism ; Animals ; Arachis ; Carbohydrate Metabolism ; Child, Preschool ; Diseases in Twins/*microbiology ; Feces/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Germ-Free Life ; Humans ; Infant ; Kwashiorkor/diet therapy/epidemiology/*microbiology ; Longitudinal Studies ; Malawi/epidemiology ; Male ; *Metagenome ; Mice ; Mice, Inbred C57BL ; }, abstract = {Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.}, }
@article {pmid23355312, year = {2013}, author = {Bridger, N and Drews, S and Burdz, T and Wiebe, D and Pacheco, AL and Ng, B and Bernard, K}, title = {Isolation and characterization of Pigmentiphaga-like isolates from human clinical material.}, journal = {Journal of medical microbiology}, volume = {62}, number = {Pt 5}, pages = {708-711}, doi = {10.1099/jmm.0.051615-0}, pmid = {23355312}, issn = {1473-5644}, mesh = {Alcaligenaceae/genetics/*isolation &amp; purification ; Child ; Feces/microbiology ; Female ; Gram-Negative Bacterial Infections/complications/*microbiology ; Humans ; Immunocompromised Host ; Liver Transplantation/adverse effects ; Otitis Media, Suppurative/complications/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Young Adult ; }, abstract = {Species in the genus Pigmentiphaga are Gram-negative, catalase- and oxidase-positive rods derived exclusively to date from environmental sources. Features of strains most like Pigmentiphaga daeguensis or Pigmentiphaga kullae from a case of suppurative otitis media in a 6-year-old female post-transplant recipient and in a human stool sample are described.}, }
@article {pmid23339948, year = {2012}, author = {Usluca, S and Inceboz, T and Unek, T and Aksoy, U}, title = {Isospora belli in a patient with liver transplantation.}, journal = {Turkiye parazitolojii dergisi}, volume = {36}, number = {4}, pages = {247-250}, doi = {10.5152/tpd.2012.58}, pmid = {23339948}, issn = {2146-3077}, mesh = {Adult ; Animals ; Anti-Infective Agents/therapeutic use ; Diarrhea/drug therapy/parasitology ; Feces/parasitology ; Humans ; Immunosuppressive Agents/administration &amp; dosage ; Isospora/classification/isolation &amp; purification ; Isosporiasis/*diagnosis/drug therapy ; *Liver Transplantation ; Male ; Occult Blood ; Oocysts ; Recurrence ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use ; }, abstract = {Isospora belli is an opportunistic protozoon which should be monitored in patients with gastrointestinal complaints such as abdominal pain, nausea and diarrhoea, in both immune-compromised and immune-competent patients. Our case was a 35 year-old male patient who had received a liver transplant because of cirrhosis and hepatic fibrosis. A diarrhoeic stool sample of the patient was sent to the laboratory for microbiological and parasitological analyses. Faecal occult blood was positive and bacteriological analysis was negative. Isospora belli infection was diagnosed by detection of the oocysts in stool samples. Per oral trimethoprim-sulphamethoxazole treatment was given in 500 mg bid dose for 10 days. At the end of the treatment, no oocyst of Isospora belli was seen but non-pathogenic cysts of Entamoeba coli and vacuolar forms of Blastocystis hominis were observed. Two months later the patient had abdominal pain, fatigue and diarrhoea again and parasitological re-evaluation showed oocysts of Isospora belli.}, }
@article {pmid23333862, year = {2013}, author = {Hamilton, MJ and Weingarden, AR and Unno, T and Khoruts, A and Sadowsky, MJ}, title = {High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria.}, journal = {Gut microbes}, volume = {4}, number = {2}, pages = {125-135}, pmid = {23333862}, issn = {1949-0984}, support = {R21 AI091907/AI/NIAID NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; R21AI091907/AI/NIAID NIH HHS/United States ; }, mesh = {Aged ; Biological Therapy/*methods ; *Biota ; Clostridium Infections/*therapy ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Feces/*microbiology ; Female ; Freezing ; Gastrointestinal Tract/*microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Fecal microbiota transplantation (FMT) is becoming a more widely used technology for treatment of recurrent Clostridum difficile infection (CDI). While previous treatments used fresh fecal slurries as a source of microbiota for FMT, we recently reported the successful use of standardized, partially purified and frozen fecal microbiota to treat CDI. Here we report that high-throughput 16S rRNA gene sequencing showed stable engraftment of gut microbiota following FMT using frozen fecal bacteria from a healthy donor. Similar bacterial taxa were found in post-transplantation samples obtained from the recipients and donor samples, but the relative abundance varied considerably between patients and time points. Post FMT samples from patients showed an increase in the abundance of Firmicutes and Bacteroidetes, representing 75-80% of the total sequence reads. Proteobacteria and Actinobacteria were less abundant (< 5%) than that found in patients prior to FMT. Post FMT samples from two patients were very similar to donor samples, with the Bacteroidetes phylum represented by a great abundance of members of the families Bacteroidaceae, Rikenellaceae and Porphyromonadaceae, and were largely comprised of Bacteroides, Alistipes and Parabacteroides genera. Members of the phylum Firmicutes were represented by Ruminococcaceae, Lachnospiraceae, Verrucomicrobiaceae and unclassified Clostridiales and members of the Firmicutes. One patient subsequently received antibiotics for an unrelated infection, resulting in an increase in the number of intestinal Proteobacteria, primarily Enterobacteriaceae. Our results demonstrate that frozen fecal microbiota from a healthy donor can be used to effectively treat recurrent CDI resulting in restoration of the structure of gut microbiota and clearing of Clostridum difficile.}, }
@article {pmid23323865, year = {2013}, author = {Kelly, CP}, title = {Fecal microbiota transplantation--an old therapy comes of age.}, journal = {The New England journal of medicine}, volume = {368}, number = {5}, pages = {474-475}, doi = {10.1056/NEJMe1214816}, pmid = {23323865}, issn = {1533-4406}, mesh = {Anti-Bacterial Agents/*therapeutic use ; *Clostridioides difficile ; Diarrhea/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Vancomycin/*therapeutic use ; }, }
@article {pmid23295696, year = {2012}, author = {Kruis, W}, title = {Specific probiotics or 'fecal transplantation'.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {30 Suppl 3}, number = {}, pages = {81-84}, doi = {10.1159/000342611}, pmid = {23295696}, issn = {1421-9875}, mesh = {Animals ; Bacteria/growth &amp; development/metabolism ; Feces/*microbiology ; Humans ; Intestines/microbiology ; Probiotics/adverse effects/*therapeutic use ; Treatment Outcome ; }, abstract = {The intestinal ecosystem consists mainly of the enteric flora and to a large extent determines intestinal but also extraintestinal health and disease. General alterations and specific molecular changes of intestinal bacteria cause local as well as systemic immune reactions. Nonantibiotic treatment of the enteric flora has a long tradition and spans a range of different interventions from nutrition to specific probiotics and complete fecal transplantation. When comparing therapy to specific probiotics and fecal transplantation, several aspects need to be considered, like biological consequences, safety and therapeutic evidence. The introduction of probiotics into therapy occurred more than hundred years ago. In contrast, experiences with fecal transplantation are more recent and more limited. Safety issues have not been definitively clarified. Because of the different biological activities of probiotics and fecal transplantation, it can be hypothesized that they may play different roles in the treatment of various diseases. More research is needed before the details, safety and therapeutic effects of bacteriotherapy for IBD become sufficiently clear.}, }
@article {pmid23319552, year = {2013}, author = {Ubeda, C and Bucci, V and Caballero, S and Djukovic, A and Toussaint, NC and Equinda, M and Lipuma, L and Ling, L and Gobourne, A and No, D and Taur, Y and Jenq, RR and van den Brink, MR and Xavier, JB and Pamer, EG}, title = {Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization.}, journal = {Infection and immunity}, volume = {81}, number = {3}, pages = {965-973}, pmid = {23319552}, issn = {1098-5522}, support = {P01-CA23766/CA/NCI NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01-AI95706/AI/NIAID NIH HHS/United States ; K23 AI095398/AI/NIAID NIH HHS/United States ; R37 AI039031/AI/NIAID NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; R01-AI42135/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteroidaceae/*physiology ; DNA, Bacterial ; Enterococcus faecium/*drug effects ; Female ; Gram-Positive Bacterial Infections/*therapy ; Intestines/*microbiology ; Mice ; Mice, Inbred C57BL ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; *Vancomycin Resistance ; }, abstract = {Bacteria causing infections in hospitalized patients are increasingly antibiotic resistant. Classical infection control practices are only partially effective at preventing spread of antibiotic-resistant bacteria within hospitals. Because the density of intestinal colonization by the highly antibiotic-resistant bacterium vancomycin-resistant Enterococcus (VRE) can exceed 10(9) organisms per gram of feces, even optimally implemented hygiene protocols often fail. Decreasing the density of intestinal colonization, therefore, represents an important approach to limit VRE transmission. We demonstrate that reintroduction of a diverse intestinal microbiota to densely VRE-colonized mice eliminates VRE from the intestinal tract. While oxygen-tolerant members of the microbiota are ineffective at eliminating VRE, administration of obligate anaerobic commensal bacteria to mice results in a billionfold reduction in the density of intestinal VRE colonization. 16S rRNA gene sequence analysis of intestinal bacterial populations isolated from mice that cleared VRE following microbiota reconstitution revealed that recolonization with a microbiota that contains Barnesiella correlates with VRE elimination. Characterization of the fecal microbiota of patients undergoing allogeneic hematopoietic stem cell transplantation demonstrated that intestinal colonization with Barnesiella confers resistance to intestinal domination and bloodstream infection with VRE. Our studies indicate that obligate anaerobic bacteria belonging to the Barnesiella genus enable clearance of intestinal VRE colonization and may provide novel approaches to prevent the spread of highly antibiotic-resistant bacteria.}, }
@article {pmid23318479, year = {2013}, author = {Brandt, LJ}, title = {American Journal of Gastroenterology Lecture: Intestinal microbiota and the role of fecal microbiota transplant (FMT) in treatment of C. difficile infection.}, journal = {The American journal of gastroenterology}, volume = {108}, number = {2}, pages = {177-185}, doi = {10.1038/ajg.2012.450}, pmid = {23318479}, issn = {1572-0241}, mesh = {Anti-Bacterial Agents/administration &amp; dosage ; Clostridioides difficile ; Clostridium Infections/microbiology/therapy ; *Enema ; Enterococcus faecalis ; Enterocolitis/drug therapy/*microbiology/*therapy ; Enterocolitis, Pseudomembranous/microbiology/therapy ; Escherichia coli ; *Feces/microbiology ; Humans ; Intestines/*microbiology ; Klebsiella pneumoniae ; *Metagenome ; Proteus mirabilis ; Staphylococcus aureus ; *Transplantation, Homologous/methods ; }, abstract = {The vital roles that intestinal flora, now called microbiota, have in maintaining our health are being increasingly appreciated. Starting with birth, exposure to the outside world begins the life-long intimate association our microbiota will have with our diet and environment, and initiates determination of the post-natal structural and functional maturation of the gut. Moreover, vital interactions of the microbiota with our metabolic activities, as well as with the immunological apparatus that constitutes our major defense system against foreign antigens continues throughout life. A perturbed intestinal microbiome has been associated with an increasing number of gastrointestinal and non-gastrointestinal diseases including Clostridium difficile infection (CDI). It has become recognized that fecal microbiota transplantation (FMT) can correct the dysbiosis that characterizes chronic CDI, and effect a seemingly safe, relatively inexpensive, and rapidly effective cure in the vast majority of patients so treated. In addition, FMT has been used to treat an array of other gastrointestinal and non-gastrointestinal disorders, although experience in these other non-CDI diseases is in its infancy. More work needs to be done with FMT to ensure its safety and optimal route of administration. There is a conceptual sea change that is developing in our view of bacteria from their role only as pathogens to that of being critical to health maintenance in a changing world. Future studies are certain to narrow the spectrum of organisms that need to be given to patients to cure disease. FMT is but the first step in this journey.}, }
@article {pmid23314803, year = {2013}, author = {Sclair, SN and Schiff, ER}, title = {An update on the hepatitis E virus.}, journal = {Current gastroenterology reports}, volume = {15}, number = {2}, pages = {304}, pmid = {23314803}, issn = {1534-312X}, mesh = {Antiviral Agents/therapeutic use ; Chemical and Drug Induced Liver Injury/diagnosis ; Coinfection/virology ; Diagnosis, Differential ; Female ; Genotype ; HIV Infections/complications ; *Hepatitis E/complications/diagnosis/drug therapy/epidemiology/virology ; Hepatitis E virus/genetics ; Humans ; Immunocompromised Host ; Neoplasms/complications/drug therapy ; Organ Transplantation ; Pregnancy ; Pregnancy Complications, Infectious/virology ; }, abstract = {There have been recent key advances in the understanding of hepatitis E virus infection. Since the early 1980s, when the virus was first discovered, hepatitis E has been described as a disease that is endemic only in the African and Asian subcontinents, a disease that is transmitted via the fecal-oral route, and a disease that causes an acute illness that typically resolves, with the exception of the third trimester of pregnancy, when infection can be deadly. We now know that genotype 3 is likely a porcine zoonotic disease that is quite prevalent in certain industrialized nations. Hepatitis E carries high morbidity and mortality in patients with underlying liver disease and can become a chronic infection that causes fibrosis in immunocompromised hosts. Lastly, two vaccines have been developed and studied in clinical trials, with excellent results.}, }
@article {pmid23313154, year = {2013}, author = {Kumar, S and Subhadra, S and Singh, B and Panda, BK}, title = {Hepatitis E virus: the current scenario.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {17}, number = {4}, pages = {e228-33}, doi = {10.1016/j.ijid.2012.11.026}, pmid = {23313154}, issn = {1878-3511}, mesh = {Animals ; *Hepatitis E/epidemiology/genetics/prevention &amp; control/transmission ; Hepatitis E virus/immunology/*pathogenicity ; Humans ; Viral Vaccines/administration &amp; dosage ; }, abstract = {Hepatitis E infection, caused by the hepatitis E virus (HEV), is a common cause of acute hepatitis in developing countries with poor sanitation and hygiene. The virus is classified into four genotypes (1-4) with one serotype. Genotypes 1 and 2 exclusively infect humans, whereas genotypes 3 and 4 also infect other animals, particularly pigs. In endemic areas, large outbreaks of acute hepatitis caused by viruses of genotype 1 or 2 frequently occur due to fecal-oral transmission, usually through contamination of drinking water. With a high attack rate in young adults (aged 15-45 years), the disease is particularly severe among pregnant women (20-30% mortality). HEV appears to be a zoonotic disease, with transmission from pigs, wild boars, and deer, or foodborne. Chronic infections are rare, except in immunosuppressed persons, such as organ transplant recipients. A subunit vaccine has been shown to be effective in preventing the clinical disease, but is not yet commercially available. Our understanding of HEV has undergone major changes in recent years and in this article we review the currently available information with regard to the molecular biology, pathobiology, and epidemiology of HEV infection. We also review the current therapeutic interventions and strategies being used to control HEV infection, with emphasis on possible approaches that could be used to develop an effective vaccine against HEV.}, }
@article {pmid23281400, year = {2013}, author = {Couturier-Maillard, A and Secher, T and Rehman, A and Normand, S and De Arcangelis, A and Haesler, R and Huot, L and Grandjean, T and Bressenot, A and Delanoye-Crespin, A and Gaillot, O and Schreiber, S and Lemoine, Y and Ryffel, B and Hot, D and Nùñez, G and Chen, G and Rosenstiel, P and Chamaillard, M}, title = {NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer.}, journal = {The Journal of clinical investigation}, volume = {123}, number = {2}, pages = {700-711}, pmid = {23281400}, issn = {1558-8238}, support = {R01 DK061707/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Colitis/*etiology/metabolism/microbiology/pathology ; Colorectal Neoplasms/*etiology/metabolism/microbiology/pathology ; Digestive System/metabolism/microbiology/pathology ; Disease Models, Animal ; Female ; Humans ; Male ; Metagenome ; Mice ; Mice, Knockout ; Nod2 Signaling Adaptor Protein/*deficiency/genetics ; Pregnancy ; Receptor-Interacting Protein Serine-Threonine Kinase 2 ; Receptor-Interacting Protein Serine-Threonine Kinases/deficiency/genetics ; Risk Factors ; }, abstract = {Instability in the composition of gut bacterial communities (dysbiosis) has been linked to common human intestinal disorders, such as Crohn's disease and colorectal cancer. Here, we show that dysbiosis caused by Nod2 deficiency gives rise to a reversible, communicable risk of colitis and colitis-associated carcinogenesis in mice. Loss of either Nod2 or RIP2 resulted in a proinflammatory microenvironment that enhanced epithelial dysplasia following chemically induced injury. The condition could be improved by treatment with antibiotics or an anti-interleukin-6 receptor-neutralizing antibody. Genotype-dependent disease risk was communicable via maternally transmitted microbiota in both Nod2-deficient and WT hosts. Furthermore, reciprocal microbiota transplantation reduced disease risk in Nod2-deficient mice and led to long-term changes in intestinal microbial communities. Conversely, disease risk was enhanced in WT hosts that were recolonized with dysbiotic fecal microbiota from Nod2-deficient mice. Thus, we demonstrated that licensing of dysbiotic microbiota is a critical component of disease risk. Our results demonstrate that NOD2 has an unexpected role in shaping a protective assembly of gut bacterial communities and suggest that manipulation of dysbiosis is a potential therapeutic approach in the treatment of human intestinal disorders.}, }
@article {pmid25525499, year = {2013}, author = {Lewis, SS and Anderson, DJ}, title = {Treatment of Clostridium difficile infection: recent trial results.}, journal = {Clinical investigation}, volume = {3}, number = {9}, pages = {875-886}, pmid = {25525499}, issn = {2041-6792}, support = {K23 AI095357/AI/NIAID NIH HHS/United States ; }, abstract = {Clostridium difficile is a major cause of infection worldwide and is associated with increasing morbidity and mortality in vulnerable patient populations. Metronidazole and oral vancomycin are the currently recommended therapies for the treatment of C. difficile infection (CDI) but are associated with unacceptably high rates of disease recurrence. Novel therapies for the treatment of CDI and prevention of recurrent CDI are urgently needed. Important developments in the treatment of CDI are currently underway and include: novel antibacterial agents with narrower antimicrobial spectra of activity, manipulation of the gut microbiota and enhancement of the host antibody immune response.}, }
@article {pmid23274737, year = {2013}, author = {Digennaro, R and Tondo, M and Cuccia, F and Giannini, I and Pezzolla, F and Rinaldi, M and Scala, D and Romano, G and Altomare, DF}, title = {Coloanal anastomosis or abdominoperineal resection for very low rectal cancer: what will benefit, the surgeon's pride or the patient's quality of life?.}, journal = {International journal of colorectal disease}, volume = {28}, number = {7}, pages = {949-957}, pmid = {23274737}, issn = {1432-1262}, mesh = {Abdomen/*surgery ; Adult ; Aged ; Aged, 80 and over ; Anal Canal/*surgery ; Anastomosis, Surgical ; Colon/*surgery ; Fecal Incontinence/etiology ; Female ; Humans ; Male ; Middle Aged ; Perineum/*surgery ; *Physicians ; *Quality of Life ; Rectal Neoplasms/complications/*surgery ; Surveys and Questionnaires ; Urinary Incontinence/etiology ; }, abstract = {PURPOSES: Sphincter-saving operation with coloanal anastomosis (CAA) has become an established option for very low rectal cancer, but few studies have compared its functional results and quality of life (QoL) with abdominoperineal resection (APR) showing controversial results.<br><br>PATIENTS AND METHODS: Patients treated for low rectal cancer with APR or CAA, disease-free after a median follow-up period of 26.5 (8-84) and 52.5 (12-156) months, respectively, were retrospectively reviewed. General and disease-specific changes in QoL and severity of disease were evaluated by Karnofsky scale, EORTC-C30, EORTC-CR38, SF-36, PGWBI, FIQL, PAC-QoL, ICIQ-SF, Stoma-QoL, AMS, Wexner's score and obstructed defecation syndrome (ODS) score.<br><br>RESULTS: Twenty-six APR patients and 34 CAA patients entered the study. Karnofsky score did not show significant differences. The median Stoma-QoL was 58.2 (45-76.6), indicating a good stoma function in 95% of patients. EORTC-C30, CR38, PGWBI and SF-36 questionnaires did not show significant differences between the two groups except for sexual function (better after CAA, p = 0.01). Eleven patients after APR and eight after CAA had urinary incontinence, and its severity did not differ significantly. Eighteen of 21 CAA patients complained of faecal incontinence [AMS, 80 (15-120); Wexner, 13 (2-19)] with an impact on their QoL [FIQL: lifestyle, 1.75 (0-4); coping/behaviour, 1.3 (0-3.5); depression, 2.1 (0-5.2); embarrassment, 2 (0-4.6)] and 11 complained of obstructed defecation [7.5 (3-16)] with significant consequences on QoL [PAC-QoL, 30.4 (19.2-80.3)].<br><br>CONCLUSIONS: QoL in patients with permanent stoma and in those after CAA did not differ significantly. APR patients had worse sexual function, while most CAA patients had faecal incontinence and sometime obstructed defecation, with important impact on their QoL.}, }
@article {pmid23274229, year = {2013}, author = {Nagy, GG and Várvölgyi, C and Balogh, Z and Orosi, P and Paragh, G}, title = {[Detailed methodological recommendations for the treatment of Clostridium difficile-associated diarrhea with faecal transplantation].}, journal = {Orvosi hetilap}, volume = {154}, number = {1}, pages = {10-19}, doi = {10.1556/OH.2013.29514}, pmid = {23274229}, issn = {0030-6002}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/isolation &amp; purification ; Diarrhea/*microbiology ; Enterocolitis, Pseudomembranous/complications/*therapy ; *Feces ; *Gastrointestinal Tract/microbiology ; Humans ; Sterilization ; Transplantation, Homologous/instrumentation/*methods ; Treatment Outcome ; }, abstract = {The incidence of Clostridium difficile associated enteral disease shows dramatic increase worldwide, with appallingly high treatment costs, mortality figures, recurrence rates and treatment refractoriness. It is not surprising, that there is significant interest in the development and introduction of alternative therapeutic strategies. Among these only stool transplantation (or faecal bacteriotherapy) is gaining international acceptance due to its excellent cure rate (≈92%), low recurrence rate (≈6%), safety and cost-effectiveness. Unfortunately faecal transplantation is not available for most patients, although based on promising international results, its introduction into the routine clinical practice is well justified and widely expected. The authors would like to facilitate this process, by presenting a detailed faecal transplantation protocol prepared in their Institution based on the available literature and clinical rationality. Officially accepted national methodological guidelines will need to be issued in the future, founded on the expert opinion of relevant professional societies and upcoming advances in this field.}, }
@article {pmid23270052, year = {2012}, author = {Stiefelhagen, P}, title = {[Success of microflora therapy: an "offensive" therapy concept not just for intestinal diseases?].}, journal = {MMW Fortschritte der Medizin}, volume = {154}, number = {21}, pages = {26, 28}, doi = {10.1007/s15006-012-1580-3}, pmid = {23270052}, issn = {1438-3276}, mesh = {Colonic Neoplasms/microbiology/therapy ; Diabetes Mellitus, Type 2/therapy ; Diarrhea/therapy ; Enterocolitis, Pseudomembranous/therapy ; Feces/*microbiology ; Humans ; Hypersensitivity/therapy ; Intestinal Diseases/*microbiology/*therapy ; Intestines/*microbiology ; Overweight/therapy ; *Transplants ; }, }
@article {pmid23261996, year = {2012}, author = {Nagy, GG and Várvölgyi, C and Paragh, G}, title = {[Successful treatment of life-threatening, treatment resistant Clostridium difficile infection associated pseudomembranous colitis with faecal transplantation].}, journal = {Orvosi hetilap}, volume = {153}, number = {52}, pages = {2077-2083}, doi = {10.1556/OH.2012.29509}, pmid = {23261996}, issn = {0030-6002}, mesh = {Anti-Infective Agents/therapeutic use ; *Clostridioides difficile ; Clostridium Infections/complications/*therapy ; Drug Resistance, Bacterial ; Enterocolitis, Pseudomembranous/diagnostic imaging/microbiology/*therapy ; *Feces ; Humans ; Hungary ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Tomography, X-Ray Computed ; Treatment Failure ; Treatment Outcome ; }, abstract = {Due to world-wide spread of hypervirulent and antibiotic resistant Clostridium difficile strains, the incidence of these infections are dramatically increasing in Hungary with appalling mortality and recurrence rates. Authors present a case of a 59-year-old patient who developed a severe, relapsing pseudomembranous colitis after antibiotic treatment. Life-threatening symptoms of fulminant colitis were successfully treated with prolonged administration of metronidazole and vancomycin, careful supportive therapy and weeks of intensive care. However, a well-documented, severe relapse developed within a week and this time faecal bacteriotherapy was performed. This treatment resulted in a complete cure without any further antibiotic treatment. In relation to this life-saving faecal transplantation, methodology and indications are briefly discussed. In addition, microbiological issues, epidemiological data and threats associated with antibiotic treatment of Clostridium difficile infections are also covered. Finally, relevant professional societies are urged to prepare a national protocol for faecal transplantation, which could allow introduction of this valuable, cost-effective procedure into the routine clinical practice.}, }
@article {pmid23261994, year = {2012}, author = {Guseo, A}, title = {[The Parkinson puzzle].}, journal = {Orvosi hetilap}, volume = {153}, number = {52}, pages = {2060-2069}, doi = {10.1556/OH.2012.29461}, pmid = {23261994}, issn = {0030-6002}, mesh = {Amino Acids, Diamino/*adverse effects ; Amyotrophic Lateral Sclerosis/epidemiology/*etiology/physiopathology ; Animals ; Chiroptera ; Cyanobacteria Toxins ; Dementia/epidemiology/etiology ; Depression/*complications ; Depressive Disorder/complications ; Duodenal Ulcer/*complications/microbiology ; Encephalitis/*complications/physiopathology ; Excitatory Amino Acid Agonists/adverse effects ; Feces ; Helicobacter Infections/*complications ; Helicobacter pylori ; Humans ; Intestines/*physiopathology ; Lewy Bodies/pathology ; Oxidative Stress ; *Parkinson Disease/epidemiology/etiology/metabolism/pathology/physiopathology ; Sleep Initiation and Maintenance Disorders/complications ; Stomach Ulcer/*complications/microbiology ; alpha-Synuclein/metabolism ; }, abstract = {Parkinson's disease is one of the most frequent progressive degenerative disorders with unknown origin of the nervous system. The commutation of the disease on Guam led to the discovery of a neurotoxin which was also found in other continents. This neurotoxin was identified in the common cyanobacteria (blue-green algae). Early clinical observations suggested some loose correlations with gastric and duodenal ulcer and Parkinson's disease, while recent studies revealed a toxin, almost identical to that found in cyanobacteria in one strain of Helicobacter pylori, which proved to cause Parkinson like symptoms in animals. Therefore, it cannot be ruled out that there is a slowly progressive poisoning in Parkinson's disease. The disease specific alpha-sinuclein inclusions can be found in nerve cells of the intestinal mucosa far before the appearance of clinical symptoms indicating that the disease may start in the intestines. These results are strengthened by the results of Borody's fecal transplants, after which in Parkinson patients showed a symptomatic improvement. Based on these observations the Parkinson puzzle is getting complete. Although these observations are not evidence based, they may indicate a new way for basic clinical research, as well as a new way of thinking for clinicians. These new observations in psycho-neuro-immunology strengthen the fact that immunological factors may also play a critical factor facilitating local cell necrosis which may be influenced easily.}, }
@article {pmid23242561, year = {2013}, author = {Puerta Díaz, JD and Castaño Llano, R and Lombana, LJ and Restrepo, JI and Gómez, G}, title = {Use of the gluteus maximus muscle as the neosphincter for restoration of anal function after abdominoperineal resection.}, journal = {Techniques in coloproctology}, volume = {17}, number = {4}, pages = {425-429}, pmid = {23242561}, issn = {1128-045X}, mesh = {Adult ; Aged ; Anal Canal/pathology/*surgery ; Buttocks/surgery ; Cohort Studies ; Colostomy/methods ; Fecal Incontinence/prevention &amp; control ; Female ; Follow-Up Studies ; Graft Survival ; Humans ; Laparotomy/methods ; Male ; Manometry ; Middle Aged ; Muscle, Skeletal/*transplantation ; Perineum/surgery ; Postoperative Care/methods ; *Quality of Life ; Plastic Surgery Procedures/*methods ; Rectal Neoplasms/pathology/*surgery ; Reoperation/methods ; Retrospective Studies ; Surgical Flaps/*blood supply ; Treatment Outcome ; Wound Healing/physiology ; }, abstract = {BACKGROUND: Our aim was to evaluate complications and long-term functional outcome in patients who had sphincter reconstruction using the gluteus maximus muscle as the neosphincter after abdominoperineal resection for rectal cancer treatment.<br><br>METHODS: Seven patients underwent reconstruction from 2000 to 2010. First, the sigmoid colon was brought down to the perineum as a perineal colostomy, with the procedure protected by a loop ileostomy. Reconstruction of the sphincter mechanism using the gluteus maximus took place 3 months later, and after another 8-12 weeks, the loop ileostomy was closed. We studied the functional outcome of these interventions with follow-up interviews of patients and objectively assessed anorectal function using manometry and the Cleveland Clinic Florida (Jorge-Wexner) fecal incontinence score.<br><br>RESULTS: The mean follow-up was 56 months (median 47; range 10-123 months). One patient had a perianal wound infection and another had fibrotic stricture in the colocutaneous anastomosis that required several digital dilatations. Anorectal manometry at 3-month follow-up showed resting pressures from 10 to 18 mm Hg and voluntary contraction pressures from 68 to 187 mm Hg. Four patients had excellent sphincter function (Jorge-Wexner scores &#x2264;5).<br><br>CONCLUSIONS: Our preliminary results show that sphincter reconstruction by means of gluteus maximus transposition can be effective in restoring gastrointestinal continuity and recovering fecal continence in patients who have undergone APR with permanent colostomy for rectal cancer. Furthermore, the reconstruction procedure can be performed 2-4 years after the APR.}, }
@article {pmid23223589, year = {2013}, author = {Jiang, ZD and Hoang, LN and Lasco, TM and Garey, KW and Dupont, HL}, title = {Physician attitudes toward the use of fecal transplantation for recurrent Clostridium difficile infection in a metropolitan area.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {56}, number = {7}, pages = {1059-1060}, doi = {10.1093/cid/cis1025}, pmid = {23223589}, issn = {1537-6591}, mesh = {*Attitude of Health Personnel ; Biological Therapy/*methods ; Clostridioides difficile/*isolation &amp; purification/pathogenicity ; Clostridium Infections/microbiology/*prevention &amp; control/therapy ; Cross Infection/microbiology/*prevention &amp; control/therapy ; Feces/*microbiology ; Humans ; *Physicians ; Secondary Prevention ; Surveys and Questionnaires ; Texas ; }, }
@article {pmid23221466, year = {2013}, author = {Sim, K and Powell, E and Shaw, AG and McClure, Z and Bangham, M and Kroll, JS}, title = {The neonatal gastrointestinal microbiota: the foundation of future health?.}, journal = {Archives of disease in childhood. Fetal and neonatal edition}, volume = {98}, number = {4}, pages = {F362-4}, doi = {10.1136/archdischild-2012-302872}, pmid = {23221466}, issn = {1468-2052}, mesh = {Gastrointestinal Tract/immunology/*microbiology ; Health Status ; Humans ; Infant, Newborn ; Metagenome/*immunology ; }, }
@article {pmid23211865, year = {2012}, author = {Kahn, SA and Young, S and Rubin, DT}, title = {Colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection in a child.}, journal = {The American journal of gastroenterology}, volume = {107}, number = {12}, pages = {1930-1931}, doi = {10.1038/ajg.2012.351}, pmid = {23211865}, issn = {1572-0241}, mesh = {*Clostridioides difficile ; *Colonoscopy ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; }, }
@article {pmid23207596, year = {2013}, author = {Pacheco, SM and Johnson, S}, title = {Important clinical advances in the understanding of Clostridium difficile infection.}, journal = {Current opinion in gastroenterology}, volume = {29}, number = {1}, pages = {42-48}, doi = {10.1097/MOG.0b013e32835a68d4}, pmid = {23207596}, issn = {1531-7056}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/isolation &amp; purification ; Enterocolitis, Pseudomembranous/*diagnosis/epidemiology/*therapy ; Feces/microbiology ; Fidaxomicin ; Humans ; Polymerase Chain Reaction ; Recurrence ; Risk Factors ; }, abstract = {PURPOSE OF REVIEW: Clostridium difficile remains an important cause of infectious colitis, particularly in healthcare facilities. This review summarizes recent advances in the epidemiology, diagnosis, and treatment of this endemic pathogen.<br><br>RECENT FINDINGS: C. difficile infection (CDI) hospitalizations and mortality rates have increased over the last decade. The BI/NAP1/027 strain has been responsible for epidemics with increased severity and mortality and is now endemic in many settings, particularly North America. Concurrent antibiotics have now been shown to decrease the cure rates for anti-C. difficile therapy and increase the risk of recurrence. Although studies implicate proton pump inhibitors as a risk for CDI, the magnitude of and the biological basis for that risk remain unclear. Molecular diagnostic techniques are rapid and sensitive but highlight the importance of using appropriate clinical testing criteria. Fidaxomicin is a promising new therapy associated with decreased recurrence; infections due to BI strains, however, are associated with inferior outcomes regardless of the treatment agent. Fecal transplantation continues to have impressive success rates for patients with recurrent CDI, and a new colon-sparing surgical procedure presents an intriguing suggested alternative to total colectomy in severe, complicated cases.<br><br>SUMMARY: Elucidating CDI risk factors, identifying rapid, accurate diagnostic tools, and validating new treatment approaches remains an urgent priority.}, }
@article {pmid23198783, year = {2012}, author = {Pondrom, S}, title = {You aren’t who you think you are: microbial cells outnumber human cells 10 to one, and could prove to be new players in transplantation.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {12}, number = {12}, pages = {3167-3168}, doi = {10.1111/ajt.12039}, pmid = {23198783}, issn = {1600-6143}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacteria/*drug effects ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; *Metagenome ; }, }
@article {pmid23182843, year = {2013}, author = {Rubin, TA and Gessert, CE and Aas, J and Bakken, JS}, title = {Fecal microbiome transplantation for recurrent Clostridium difficile infection: report on a case series.}, journal = {Anaerobe}, volume = {19}, number = {}, pages = {22-26}, doi = {10.1016/j.anaerobe.2012.11.004}, pmid = {23182843}, issn = {1095-8274}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biological Therapy/*methods ; Child ; Clostridioides difficile/*pathogenicity ; Clostridium Infections/microbiology/*therapy ; Female ; Humans ; Intubation, Gastrointestinal ; Male ; Metagenome/*physiology ; Middle Aged ; Minnesota ; Retrospective Studies ; Secondary Prevention ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) continues to increase in incidence and severity, and was the most common nosocomial infection in the USA in 2010. Most cases of CDI respond to a standard course of antibiotics, but recurrent C. difficile infection (RCDI) has become increasingly frequent, and alternative treatments are needed. We examined the efficacy of fecal microbiota transplantation (FMT) instilled into the upper gastrointestinal tract for RCDI.<br><br>MATERIALS AND METHODS: The medical records for all patients treated with FMT during a 9-year period at a single institution in northern Minnesota were reviewed retrospectively. Eighty-nine FMT courses were provided by nasogastric tube to 87 patients, and demographic and clinical data were abstracted, including details of treatments prior to FMT, rate of FMT treatment success and clinical course during a 60-day post FMT follow up period. Fourteen FMT courses failed to meet criteria for inclusion.<br><br>RESULTS: Each patient served as his or her own control, having failed standard treatment. After exclusions, the case series included 75 FMT courses administered to 74 patients. Fifty-nine FMT courses resulted in clinical resolution of diarrhea for a primary cure rate of 79%. Diarrhea relapsed following 16 FMT courses; in 9 of these cases diarrhea subsequently resolved after a single course of vancomycin. No adverse events were noted.<br><br>CONCLUSIONS: Our findings parallel findings from other studies when FMT has been provided via the upper GI tract, and suggest that patients with recurrent CDI may resolve diarrhea by introducing stool from healthy donors into the upper GI tract via nasogastric tube.}, }
@article {pmid23182812, year = {2013}, author = {Wong, G and Li, MW and Howard, K and Hua, DK and Chapman, JR and Bourke, M and Turner, R and Tong, A and Craig, JC}, title = {Health benefits and costs of screening for colorectal cancer in people on dialysis or who have received a kidney transplant.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {28}, number = {4}, pages = {917-926}, doi = {10.1093/ndt/gfs490}, pmid = {23182812}, issn = {1460-2385}, mesh = {Aged ; Colorectal Neoplasms/diagnosis/*economics ; Cost-Benefit Analysis ; Female ; Follow-Up Studies ; Humans ; Kidney Function Tests ; Kidney Transplantation/adverse effects/*economics ; Male ; Markov Chains ; Mass Screening/*economics ; Middle Aged ; Prognosis ; Prospective Studies ; Quality-Adjusted Life Years ; Renal Dialysis/*economics ; Renal Insufficiency, Chronic/complications/*economics/therapy ; Survival Rate ; }, abstract = {BACKGROUND: Despite the higher risk of colorectal cancer (CRC) in people with chronic kidney disease, it remains uncertain whether early detection through screening is cost-effective in this setting. We aimed to determine the costs and health benefits of CRC screening in people on dialysis or who have received a kidney transplant.<br><br>METHODS: Using a government health perspective, three probabilistic Markov models were constructed to compare the cost-effectiveness and cost-utility of annual immunochemical faecal occult blood test (iFOBT) screening against no-screening in a cohort of 1000 patients (age 50-70 years) on dialysis and with kidney transplants. A series of one-way, multi-way and probabilistic sensitivity analyses were conducted to assess the robustness of the model structure and the extent in which the model's assumptions were sensitive to the uncertainties within the input variables.<br><br>RESULTS: The incremental cost-effectiveness ratios (ICERs) of CRC screening compared with no-screening were $138 828 per quality-adjusted life year [QALY; $122 977 per life year saved (LYS)], $121 973 per QALY ($ 85 095 per LYS) and $44 790 per QALY ($25 036 per LYS) for dialysis patients not listed on the transplant waiting list, patients on the transplant waiting list and patients with kidney transplants, respectively. The test specificity of iFOBT, the starting age of screening and cancer prevalence were influential factors that determined the overall cost-effectiveness of screening in this setting.<br><br>CONCLUSION: Screening for CRC using iFOBT may reduce cancer-specific mortality in patients on dialysis and with kidney transplants. However, the benefits and costs of screening CRCs in patients on dialysis, especially for those deemed not suitable for transplantation, greatly exceeded the typical thresholds for acceptable cost-effectiveness.}, }
@article {pmid23175663, year = {2012}, author = {Chiusolo, P and Metafuni, E and Giammarco, S and Bellesi, S and Piccirillo, N and Fanali, C and Castagnola, M and Zuppi, C and De Michele, T and Leone, G and Sica, S}, title = {Role of fecal calprotectin as biomarker of gastrointestinal GVHD after allogeneic stem cell transplantation.}, journal = {Blood}, volume = {120}, number = {22}, pages = {4443-4444}, doi = {10.1182/blood-2012-08-447326}, pmid = {23175663}, issn = {1528-0020}, mesh = {Biomarkers/analysis ; Case-Control Studies ; Cohort Studies ; Feces/*chemistry ; Gastrointestinal Diseases/*diagnosis/epidemiology/etiology ; Graft vs Host Disease/complications/*diagnosis/epidemiology ; Hematologic Diseases/epidemiology/therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects/statistics &amp; numerical data ; Humans ; Leukocyte L1 Antigen Complex/*analysis/*physiology ; Predictive Value of Tests ; ROC Curve ; Transplantation, Homologous/adverse effects ; }, }
@article {pmid23172281, year = {2012}, author = {Kim, SY and Kwon, JG and Kim, MH and Oh, JY and Park, JH and Park, KC and Ryoo, JI and Ryoo, HM}, title = {[A case of acute lymphoblastic leukemia presenting with protein-losing enteropathy].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {60}, number = {5}, pages = {320-324}, doi = {10.4166/kjg.2012.60.5.320}, pmid = {23172281}, issn = {2233-6869}, mesh = {Adult ; Bone Marrow Cells/pathology ; Endoscopy, Gastrointestinal ; Humans ; Magnetic Resonance Imaging ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications/*diagnosis/genetics ; Protein-Losing Enteropathies/complications/*diagnosis ; Thoracic Vertebrae/diagnostic imaging ; Tomography, X-Ray Computed ; Translocation, Genetic ; alpha 1-Antitrypsin/analysis ; }, abstract = {Protein-losing enteropathy (PLE) is a syndrome characterized by excessive gastrointestinal protein loss, resulting in hypoproteinemia and edema. A variety of benign and malignant conditions can be associated with PLE and acute leukemia is a very rare cause of PLE. We report a case of PLE associated with acute lymphoblastic leukemia. A 27-year-old man was admitted due to watery diarrhea, epigastric pain and bilateral leg edema. Laboratory findings showed hypoproteinemia and polycythemia. The diagnosis of PLE and acute lymphoblastic leukemia were confirmed on the measurement of fecal a1-antitrypsin clearance and bone marrow examination. After systemic chemotherapy and autologous stem cell transplantation, his clinical symptoms and abnormal laboratory findings were gradually improved.}, }
@article {pmid23163886, year = {2013}, author = {Sofi, AA and Silverman, AL and Khuder, S and Garborg, K and Westerink, JM and Nawras, A}, title = {Relationship of symptom duration and fecal bacteriotherapy in Clostridium difficile infection-pooled data analysis and a systematic review.}, journal = {Scandinavian journal of gastroenterology}, volume = {48}, number = {3}, pages = {266-273}, doi = {10.3109/00365521.2012.743585}, pmid = {23163886}, issn = {1502-7708}, mesh = {*Biological Therapy/adverse effects ; *Clostridioides difficile ; Confidence Intervals ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Odds Ratio ; Time Factors ; }, abstract = {OBJECTIVE: Clostridium difficle-associated infection (CDI) is usually treated with antibiotics; nevertheless, the infection has a high relapse rate. Case series and case reports using fecal microbiota transplant (FMT) for CDI show promising results. However, there are no large studies to provide evidence for the efficacy of this therapy. The aim of this pooled patient data meta-analysis was to determine the efficacy of FMT in CDI.<br><br>METHODS: We performed a literature search for FMT for CDI or pseudomembranous colitis. Individual patient data were obtained from each study. The primary endpoint was to assess the rate of diarrhea resolution. Secondary endpoints were to identify variables associated with treatment failure and side effects of therapy.<br><br>RESULTS: A total of 289 patients from 25 published articles who received FMT for CDI were included in the pooled data analysis. FMT had an overall success rate of 91.2%. On univariate analysis, shorter duration of symptoms before FMT (< 60 days) and gastroduodenal route of fecal instillation were associated with treatment failure. On multivariate regression analysis, shorter duration of symptoms (< 60 days) before the FMT (OR= 11.08; p = 0.0009) was associated with treatment failure. Reported adverse events following FMT were irritable bowel syndrome (n = 1), symptoms of mild enteritis (n = 3), and suspected peritonitis following the procedure (n = 1).<br><br>CONCLUSION: FMT is a safe and effective treatment option for CDI. Shorter duration of symptoms (< 60 days) before administering FMT is associated with treatment failure.}, }
@article {pmid23160295, year = {2012}, author = {Zhang, F and Luo, W and Shi, Y and Fan, Z and Ji, G}, title = {Should we standardize the 1,700-year-old fecal microbiota transplantation?.}, journal = {The American journal of gastroenterology}, volume = {107}, number = {11}, pages = {1755; author reply p.1755-6}, doi = {10.1038/ajg.2012.251}, pmid = {23160295}, issn = {1572-0241}, mesh = {*Clostridioides difficile ; *Colonoscopy ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; }, }
@article {pmid23152734, year = {2012}, author = {Rohlke, F and Stollman, N}, title = {Fecal microbiota transplantation in relapsing Clostridium difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {5}, number = {6}, pages = {403-420}, pmid = {23152734}, issn = {1756-2848}, abstract = {Clostridium difficile infection rates are Climbing in frequency and severity, and the spectrum of susceptible patients is expanding beyond the traditional scope of hospitalized patients receiving antibiotics. Fecal microbiota transplantation is becoming increasingly accepted as an effective and safe intervention in patients with recurrent disease, likely due to the restoration of a disrupted microbiome. Cure rates of > 90% are being consistently reported from multiple centers. Transplantation can be provided through a variety of methodologies, either to the lower proximal, lower distal, or upper gastrointestinal tract. This review summarizes reported results, factors in donor selection, appropriate patient criteria, and the various preparations and mechanisms of fecal microbiota transplant delivery available to clinicians and patients.}, }
@article {pmid23147650, year = {2013}, author = {Salcedo, L and Mayorga, M and Damaser, M and Balog, B and Butler, R and Penn, M and Zutshi, M}, title = {Mesenchymal stem cells can improve anal pressures after anal sphincter injury.}, journal = {Stem cell research}, volume = {10}, number = {1}, pages = {95-102}, pmid = {23147650}, issn = {1876-7753}, support = {UL1 TR000439/TR/NCATS NIH HHS/United States ; }, mesh = {Anal Canal/injuries/*physiopathology ; Animals ; Cells, Cultured ; Disease Models, Animal ; Electromyography ; Fecal Incontinence/physiopathology/therapy ; Female ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*cytology ; Obstetric Labor Complications ; Pregnancy ; Pressure ; Pudendal Nerve/injuries/*physiopathology ; Rats ; Rats, Sprague-Dawley ; Wound Healing ; }, abstract = {OBJECTIVE: Fecal incontinence reduces the quality of life of many women but has no long-term cure. Research on mesenchymal stem cell (MSC)-based therapies has shown promising results. The primary aim of this study was to evaluate functional recovery after treatment with MSCs in two animal models of anal sphincter injury.<br><br>METHODS: Seventy virgin female rats received a sphincterotomy (SP) to model episiotomy, a pudendal nerve crush (PNC) to model the nerve injuries of childbirth, a sham SP, or a sham PNC. Anal sphincter pressures and electromyography (EMG) were recorded after injury but before treatment and 10 days after injury. Twenty-four hours after injury, each animal received either 0.2 ml saline or 2 million MSCs labelled with green fluorescing protein (GFP) suspended in 0.2 ml saline, either intravenously (IV) into the tail vein or intramuscularly (IM) into the anal sphincter.<br><br>RESULTS: MSCs delivered IV after SP resulted in a significant increase in resting anal sphincter pressure and peak pressure, as well as anal sphincter EMG amplitude and frequency 10 days after injury. MSCs delivered IM after SP resulted in a significant increase in resting anal sphincter pressure and anal sphincter EMG frequency but not amplitude. There was no improvement in anal sphincter pressure or EMG with in animals receiving MSCs after PNC. GFP-labelled cells were not found near the external anal sphincter in MSC-treated animals after SP.<br><br>CONCLUSION: MSC treatment resulted in significant improvement in anal pressures after SP but not after PNC, suggesting that MSCs could be utilized to facilitate recovery after anal sphincter injury.}, }
@article {pmid23142084, year = {2013}, author = {Dias, SR and da Costa, AF and Gazzinelli-Guimarães, PH and Roatt, BM and da Silva Fonseca, K and de Paiva, NC and Giunchetti, RC and Carneiro, CM and Fujiwara, RT and Rabelo, &#xc9;M}, title = {Prednisolone and cyclosporine A: effects on an experimental model of ancylostomiasis.}, journal = {Experimental parasitology}, volume = {133}, number = {1}, pages = {80-88}, doi = {10.1016/j.exppara.2012.10.008}, pmid = {23142084}, issn = {1090-2449}, mesh = {Ancylostomiasis/*drug therapy/immunology ; Animals ; Cell Proliferation/drug effects ; Cricetinae ; Cyclosporine/pharmacology/*therapeutic use ; Disease Models, Animal ; Feces/parasitology ; Female ; Glucocorticoids/pharmacology/*therapeutic use ; Immunoglobulin G/blood ; Immunosuppressive Agents/pharmacology/*therapeutic use ; Intestine, Small/parasitology/pathology ; Lymph Nodes/cytology/drug effects/immunology ; Mesentery ; Mesocricetus ; Parasite Egg Count ; Prednisolone/pharmacology/*therapeutic use ; Spleen/pathology ; }, abstract = {Corticosteroids and cyclosporine A (CsA) are important clinical immunosuppressive drugs used in the maintenance of organ transplants and in suppressing undesired autoimmune or allergic immune responses. To study the effect of CsA and prednisolone on the course of an Ancylostoma ceylanicum infection, hamsters were treated with commercially available prednisolone or CsA. For both drugs, half the recommended dose was sufficient to inhibit the proliferation of more than 70% of hamster lymph node cells. There was no difference in the recovery of adult worms; however, animals treated with prednisolone presented with low egg counts in the feces. Infection with A. ceylanicum resulted in an increase in specific antibodies against adult worm antigens, but hamsters treated with either drug presented with lower IgG titers. We observed that A. ceylanicum infection caused peripheral cellular immune suppression, which is characterized by a reduction in the total white cell count, neutropenia and lymphopenia. We also observed a lymphoplasmacytic pattern and few eosinophils in the mucosal inflammatory infiltrate for all the animals. The animals treated with prednisolone showed changes in the architecture of the intestine, including the loss of the mucosa, intense congestion and inflammation. In spleen, we observed hyperplasia of white pulp in all infected animals; in addition, there was a loss of tissue architecture in the animals treated with prednisolone. In conclusion, this work shows that an A. ceylanicum infection leads to acute peripheral cellular immune suppression in hamsters but not humoral immune suppression and that CsA treatment does not interfere with the process of infection. However, prednisolone treatment causes intestinal injury, what could hamper the parasite attachment to the intestinal wall, and as a result affects copulation and, consequently, decreases the number of eggs eliminated in the feces. Moreover, the possibility that the drug can also be exerting an effect on female fertility should be considered.}, }
@article {pmid23127735, year = {2012}, author = {Khanna, S and Pardi, DS}, title = {Clostridium difficile infection: new insights into management.}, journal = {Mayo Clinic proceedings}, volume = {87}, number = {11}, pages = {1106-1117}, pmid = {23127735}, issn = {1942-5546}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Anti-Infective Agents/*therapeutic use ; Clostridium Infections/diagnosis/*drug therapy ; Diarrhea/microbiology ; Humans ; Infection Control/*methods ; *Methicillin-Resistant Staphylococcus aureus ; Metronidazole/therapeutic use ; Vancomycin/therapeutic use ; }, abstract = {Clostridium difficile was first described as a cause of diarrhea in 1978 and is now among the leading 3 hospital-acquired infections in the United States, along with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. In the past 2 decades, there has been an increase in the incidence, severity, and recurrence rates of C difficile infection, all of which are associated with poor outcomes. In addition, several novel risk factors and newer treatment methods are emerging, including fidaxomicin therapy, treatment using monoclonal antibodies, and fecal microbiota transplantation, that have shown promise for the treatment of C difficile infection. This review focuses on the changing epidemiology, risk factors, and newer methods for treatment of C difficile infection.}, }
@article {pmid23121625, year = {2012}, author = {Neemann, K and Eichele, DD and Smith, PW and Bociek, R and Akhtari, M and Freifeld, A}, title = {Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {14}, number = {6}, pages = {E161-5}, doi = {10.1111/tid.12017}, pmid = {23121625}, issn = {1399-3062}, mesh = {Clostridioides difficile ; Enterocolitis, Pseudomembranous/etiology/*therapy ; Feces/*microbiology ; Female ; Humans ; Immunocompromised Host ; Intestines/microbiology ; Stem Cell Transplantation/*adverse effects ; Treatment Outcome ; Young Adult ; }, abstract = {We present a case of severe Clostridium difficile infection (CDI) in a non-neutropenic allogeneic hematopoietic stem cell transplant recipient who was treated successfully with fecal microbiota therapy after standard pharmacologic therapy had failed. Following naso-jejunal instillation of donor stool, the patient's symptoms resolved within 48 h. Bowel resection was averted. This is the first case in the literature, to our knowledge, to describe fecal microbiota therapy in a profoundly immunocompromised host with severe CDI. We propose that fecal microbiota therapy be considered as a therapeutic option in immunosuppressed patients with refractory severe CDI.}, }
@article {pmid23117471, year = {2013}, author = {Trubiano, JA and Gardiner, B and Kwong, JC and Ward, P and Testro, AG and Charles, PG}, title = {Faecal microbiota transplantation for severe Clostridium difficile infection in the intensive care unit.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {25}, number = {2}, pages = {255-257}, doi = {10.1097/MEG.0b013e32835b2da9}, pmid = {23117471}, issn = {1473-5687}, mesh = {Aged ; *Clostridioides difficile ; Combined Modality Therapy ; Critical Care/methods ; Enterocolitis, Pseudomembranous/*therapy ; Fatal Outcome ; Feces/*microbiology ; Female ; Gastroscopy ; Humans ; Metagenome ; }, abstract = {We describe a case of faecal microbiota transplantation (FMT) used for severe binary toxin-positive Clostridium difficile infection in an intensive care setting. The patient was admitted to the ICU of a tertiary hospital and failed traditional maximal pharmacological management. Adjunctive therapy with FMT given through gastroscopy resulted in resolution of the C. difficile-related symptoms. Although there is a growing experience with FMT for recurrent C. difficile infection, published evidence in severe disease is very limited. In a landscape of increasingly severe C. difficile infection, adjunctive FMT may be considered a useful early treatment option.}, }
@article {pmid23111123, year = {2013}, author = {Verma, R and Khanna, P}, title = {Development of Toxoplasma gondii vaccine: A global challenge.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {9}, number = {2}, pages = {291-293}, pmid = {23111123}, issn = {2164-554X}, mesh = {Animals ; Cats ; Disease Transmission, Infectious/prevention &amp; control ; Drug Discovery/trends ; Humans ; Protozoan Vaccines/*immunology/*isolation &amp; purification ; Sheep ; Toxoplasma/*immunology ; Toxoplasmosis, Animal/immunology/*prevention &amp; control ; Vaccination/*methods ; Zoonoses/immunology/*prevention &amp; control ; }, abstract = {Toxoplasmosis is caused by the protozoan parasite T. gondii. Humans and other warm-blooded animals are its hosts. The infection has a worldwide distribution; one-third of the world's population has been exposed to this parasite. There are three primary ways of transmission: ingesting uncooked meat containing tissue cysts, ingesting food and water contaminated with oocysts from infected cat feces and congenitally. Those particularly at risk of developing clinical illness include pregnant women, given that the parasite can pose a serious threat to the unborn child if the mother becomes infected while pregnant, and immunosuppressed individuals such as tissue transplant subjects, AIDS subjects, those with certain types of cancer and those undergoing certain forms of cancer therapy. Maternal infections early in pregnancy are less likely to be transmitted to the fetus than infections later in pregnancy, but early fetal infections are more likely to be severe than later infections. In the absence of an effective human vaccine, prevention of zoonotic transmission might be the best way to approach the problem of toxoplasmosis and must be done by limiting exposure to oocysts or tissue cysts. Vaccine development to prevent feline oocyst shedding is ongoing, mostly with live vaccines. The S48 strain Toxovax is a live vaccine originally developed for use in sheep, but when used in cats inhibits sexual development of T. gondii. This vaccine is used in sheep to reduce tissue cyst development. The T-263 strain of T. gondii is a live mutant strain designed to reduce or prevent oocyst shedding by cats by developing only partial infection in the feline intestinal tract.}, }
@article {pmid23101687, year = {2012}, author = {Borody, TJ and Campbell, J}, title = {Fecal microbiota transplantation: techniques, applications, and issues.}, journal = {Gastroenterology clinics of North America}, volume = {41}, number = {4}, pages = {781-803}, doi = {10.1016/j.gtc.2012.08.008}, pmid = {23101687}, issn = {1558-1942}, mesh = {Biological Therapy/*methods ; *Clostridioides difficile ; Colitis, Ulcerative/microbiology/*therapy ; Diarrhea/microbiology/therapy ; Enema ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Intubation, Gastrointestinal ; Metagenome ; }, abstract = {Fecal microbiota transplantation (FMT) has gained widespread recognition in light of the recent Clostridium difficile infection (CDI) epidemic, responsible for almost 110,000 deaths per year. The procedure's success rate has caused experts to reflect on what other conditions may benefit. This article provides an overview of (1) description and history of FMT, (2) FMT publications in CDI, (3) the concept of the gut microbiota as a virtual organ, (4) rationale for FMT use, (5) FMT use in inflammatory bowel disease, (6) emerging FMT applications, (7) how FMT is currently performed, and (8) how FMT may be performed in the future.}, }
@article {pmid23093385, year = {2012}, author = {Shahinas, D and Silverman, M and Sittler, T and Chiu, C and Kim, P and Allen-Vercoe, E and Weese, S and Wong, A and Low, DE and Pillai, DR}, title = {Toward an understanding of changes in diversity associated with fecal microbiome transplantation based on 16S rRNA gene deep sequencing.}, journal = {mBio}, volume = {3}, number = {5}, pages = {}, pmid = {23093385}, issn = {2150-7511}, mesh = {Clostridioides difficile/pathogenicity ; Clostridium Infections/*therapy ; Feces/*microbiology ; Genes, rRNA/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenome/genetics/*physiology ; }, abstract = {Fecal microbiome transplantation by low-volume enema is an effective, safe, and inexpensive alternative to antibiotic therapy for patients with chronic relapsing Clostridium difficile infection (CDI). We explored the microbial diversity of pre- and posttransplant stool specimens from CDI patients (n = 6) using deep sequencing of the 16S rRNA gene. While interindividual variability in microbiota change occurs with fecal transplantation and vancomycin exposure, in this pilot study we note that clinical cure of CDI is associated with an increase in diversity and richness. Genus- and species-level analysis may reveal a cocktail of microorganisms or products thereof that will ultimately be used as a probiotic to treat CDI. IMPORTANCE Antibiotic-associated diarrhea (AAD) due to Clostridium difficile is a widespread phenomenon in hospitals today. Despite the use of antibiotics, up to 30% of patients are unable to clear the infection and suffer recurrent bouts of diarrheal disease. As a result, clinicians have resorted to fecal microbiome transplantation (FT). Donor stool for this type of therapy is typically obtained from a spouse or close relative and thoroughly tested for various pathogenic microorganisms prior to infusion. Anecdotal reports suggest a very high success rate of FT in patients who fail antibiotic treatment (>90%). We used deep-sequencing technology to explore the human microbial diversity in patients with Clostridium difficile infection (CDI) disease after FT. Genus- and species-level analysis revealed a cocktail of microorganisms in the Bacteroidetes and Firmicutes phyla that may ultimately be used as a probiotic to treat CDI.}, }
@article {pmid23088420, year = {2012}, author = {Izadi, M and Jonaidi-Jafari, N and Saburi, A and Eyni, H and Rezaiemanesh, MR and Ranjbar, R}, title = {Prevalence, molecular characteristics and risk factors for cryptosporidiosis among Iranian immunocompromised patients.}, journal = {Microbiology and immunology}, volume = {56}, number = {12}, pages = {836-842}, doi = {10.1111/j.1348-0421.2012.00513.x}, pmid = {23088420}, issn = {1348-0421}, mesh = {Adult ; CD4 Lymphocyte Count ; Cryptosporidiosis/*epidemiology/*parasitology/pathology ; Cryptosporidium/*classification/genetics/*isolation &amp; purification ; DNA, Protozoan/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Feces/parasitology ; Female ; Genes, rRNA ; Humans ; *Immunocompromised Host ; Iran ; Male ; Middle Aged ; Prevalence ; RNA, Protozoan/genetics ; RNA, Ribosomal, 18S/genetics ; Risk Factors ; Sequence Analysis, DNA ; }, abstract = {Cryptosporidium spp. is a major cause of diarrhea in developing countries, mainly affecting people with compromised immune systems in general and HIV-infected individuals with low CD4 + T-cell counts in particular. This infection is self-limiting in healthy persons; however, it can be severe, progressive and persistent in those who are immunocompromised. There are few published studies concerning cryptosporidiosis and Cryptosporidium genotypes in Iranian immunocompromised patients and none of them describe risk factors. This study was undertaken to identify prevalence, genotypes and risk factors for cryptosporidiosis in immunocompromised patients. Three fecal samples were obtained at two day intervals from each of the 183 patients and processed with modified Ziehl-Neelsen staining methods and 18S rRNA gene amplification and sequencing. The overall infection prevalence was 6%. Cryptosporidium parvum was identified in isolates from five HIV-infected patients, one patient who had undergone bone marrow transplantation and one with chronic lymphocytic leukemia. Cryptosporidium hominis was identified in isolates from two HIV-infected patients and two patients with acute lymphocytic leukemia. According to univariate analysis, the statistically significant factors were diarrhea (OR = 21.7, CI = 2.83-78.4, P= 0.003), CD4 + lymphocytes less than 100 cells/mm(3) (OR = 41.3, CI = 13.45-114.8, P < 0.0001), other microbial infections (OR = 7.1321.7, CI = 1.97-25.73, P = 0.006), weight loss (OR = 73.78, CI = 15.5-350, P < 0.0001), abdominal pain (OR = 10.29, CI = 2.81-37.74.4, P= 0.001), dehydration (OR = 72.1, CI = 17.6-341.5, P < 0.0001), vomiting (OR = 4.87, CI = 1.4-16.9, P= 0.015), nausea (OR = 9.4, CI = 2.38-37.2, P < 0.001), highly active antiretroviral therapy (OR = 0.089, CI = 0.01-0.8, P= 0.015) and diarrhea in household members (OR = 7.37, CI = 2.04-26.66, P= 0.001). After multivariate analysis and a backward deletion process, only < 100 CD4 + T-lymphocytes/mm(3) maintained a significant association with infection. The authors recommend that this infection should be suspected in patients with diarrhea, weight loss and dehydration in general and in diarrheal individuals with < 100 CD4 + T-lymphocytes/mm(3).}, }
@article {pmid23085018, year = {2013}, author = {Chandurvelan, R and Marsden, ID and Gaw, S and Glover, CN}, title = {Field-to-laboratory transport protocol impacts subsequent physiological biomarker response in the marine mussel, Perna canaliculus.}, journal = {Comparative biochemistry and physiology. Part A, Molecular &amp; integrative physiology}, volume = {164}, number = {1}, pages = {84-90}, doi = {10.1016/j.cbpa.2012.10.011}, pmid = {23085018}, issn = {1531-4332}, mesh = {Ammonia/metabolism ; Animals ; Biomarkers/metabolism ; Chlorophyta/metabolism ; Energy Metabolism ; Feces/chemistry ; *Handling, Psychological ; Marine Biology/*methods ; Oxygen/metabolism ; Perna/metabolism/*physiology ; Respiratory Rate ; Salinity ; Seawater ; *Stress, Physiological ; Temperature ; Time Factors ; Transportation ; }, abstract = {The transfer of mussels from field to laboratory, or transplantation between clean and contaminated field settings, is a common protocol in ecotoxicology. However, collection and transport of mussels could lead to stress that may impact biomarker responses, and thus confound interpretation of results. Physiological responses (clearance rate, absorption efficiency, excretion rate, respiration rate and scope-for-growth) of green-lipped mussels (Perna canaliculus) exposed to four different transportation protocols were investigated. These protocols included immersion in site seawater (SSW), immersion in artificial seawater (ASW), and emersion (aerial transport; EMS) at two temperatures (15°C and 5°C). Physiological measurements were conducted after a simulated 24h "transport" phase and a 48h "recovery" phase. Clearance rates were significantly inhibited by the EMS 5°C and ASW protocols relative to SSW treatment, although the clearance rate of the latter recovered after 48h. A similar pattern was observed for excretion and respiration rates for ASW. Decreased excretion rates for EMS 15°C and respiration rates for EMS 5°C were also recorded relative to values for SSW following "recovery". Negative scope-for-growth was observed for all treatments except EMS 15°C. These data suggest transport emersed at ambient air temperatures is the best method to maintain physiological health of green-lipped mussels.}, }
@article {pmid23061709, year = {2012}, author = {Muraji, T}, title = {Early detection of biliary atresia: past, present &amp; future.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {6}, number = {5}, pages = {583-589}, doi = {10.1586/egh.12.37}, pmid = {23061709}, issn = {1747-4132}, mesh = {Age Factors ; Biliary Atresia/*diagnosis/history/surgery ; Diagnostic Techniques, Digestive System/*trends ; Early Diagnosis ; Feces/chemistry ; History, 20th Century ; History, 21st Century ; Humans ; Portoenterostomy, Hepatic ; Prognosis ; }, abstract = {The age threshold at the time of Kasai hepatic portoenterostomy associated with a prognosis of biliary atresia (BA) is becoming clearer as 10-year native liver survival data become more frequent in the recent literature, whereas the age at diagnosis has not dramatically decreased during the last 3 decades. A stool color card screening implemented in 1994 in Japan is now expanding worldwide. However, the contribution of this modality will probably be limited because of the nature of this disease, for example, 'progressive obliterative cholangiopathy'. A cholic stool was actually observed only in 50% before diagnosis according to the Japanese BA Registry data. Thus, color card screening does not appear to be instrumental in detecting patients with BA early enough before 1 month of age. A highly sensitive, adequately specific, noninvasive and quantitative method may be expensive, but the overall cost would be lower than that of liver transplant.}, }
@article {pmid23043783, year = {2012}, author = {Crepeau, R and Matar, A and Spitzer, TR and Robson, S and Pathiraja, V and Sachs, DH and Huang, CA and Duran-Struuck, R}, title = {Edema and tetraparesis in a miniature pig after allogeneic hematopoietic cell transplantation.}, journal = {Comparative medicine}, volume = {62}, number = {4}, pages = {298-302}, pmid = {23043783}, issn = {2769-819X}, support = {R01 AI084657/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Animals, Laboratory ; Anti-Bacterial Agents/therapeutic use ; Cyclosporine/therapeutic use ; Edema/etiology/pathology/*veterinary ; Escherichia coli Infections/complications/drug therapy/pathology/*veterinary ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Leukocyte Count/veterinary ; Male ; Somatosensory Disorders/etiology/pathology/*veterinary ; Swine ; Swine Diseases/drug therapy/*microbiology/pathology ; *Swine, Miniature ; }, abstract = {A 3-mo-old, 12-kg, intact, miniature pig presented with severe neurologic signs on day 8 after hematopoietic cell transplantation. This pig had received an immunosuppressive regimen before transplantation that included an antiCD3 immunotoxin for T-cell depletion, 100 cGy of total-body irradiation, and cyclosporine for 45 d. The pig began exhibiting erythematous lesions on posttransplantation day 7. He also demonstrated increased conscious proprioceptive deficits and recumbency but normal mentation. Neurologic signs worsened over several days; the pig became lethargic but remained afebrile. Conjunctival swelling developed on posttransplantation day 9, which subsequently spread to the animal's head, ears and hocks by day 10. Analgesics were given for pain, and cyclosporine levels were decreased. Despite the measures taken, neurologic signs progressed. Given the worsening subcutaneous edema and neurologic status, Escherichia coli infection was suspected, and treatment with a third-generation cephalosporin was instituted. The clinical signs resolved within 12 h after the start of antibiotics. 'Shiga-like' toxin from E. coli can cause peracute toxemia and induce ataxia, paralysis, and recumbency. Other common and pathognomonic findings include periocular edema and variable edema in other subcutaneous regions. A fecal sample demonstrated an overgrowth of gram-negative, lactose-fermenting colonies. On the basis of the clinical presentation, exclusion of other potential conditions compatible with edema and neurologic diseases, physical exam findings, microbiology and the resolution of signs after therapy, the pig was diagnosed with edema disease.}, }
@article {pmid23041678, year = {2013}, author = {Aroniadis, OC and Brandt, LJ}, title = {Fecal microbiota transplantation: past, present and future.}, journal = {Current opinion in gastroenterology}, volume = {29}, number = {1}, pages = {79-84}, doi = {10.1097/MOG.0b013e32835a4b3e}, pmid = {23041678}, issn = {1531-7056}, mesh = {Autistic Disorder/therapy ; Autoimmune Diseases/therapy ; *Clostridioides difficile ; Constipation/therapy ; Donor Selection ; Enterocolitis, Pseudomembranous/*therapy ; Fatigue Syndrome, Chronic/therapy ; Feces/*microbiology ; Humans ; Inflammatory Bowel Diseases/*therapy ; Irritable Bowel Syndrome/therapy ; Nervous System Diseases/therapy ; Obesity/therapy ; Recurrence ; }, abstract = {PURPOSE OF REVIEW: Fecal microbiota transplantation (FMT) re-establishes a balanced intestinal flora with resultant cure of recurrent Clostridium difficile infection (RCDI). FMT has also been used to treat other gastrointestinal (GI) diseases including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and chronic constipation and a variety of non-GI disorders. The purpose of this review is to discuss the intestinal microbiota and FMT treatment of GI and non-GI diseases.<br><br>RECENT FINDINGS: It is known that an imbalanced intestinal microbiota predisposes to CDI, IBD and IBS. The complex role of intestinal microbiota to maintain health, however, is a newer concept that is being increasingly studied. The microbiome plays an important role in cellular immunity and energy metabolism and has been implicated in the pathogenesis of non-GI autoimmune diseases, chronic fatigue syndrome, obesity and even some neuropsychiatric disorders.<br><br>SUMMARY: FMT is a highly effective cure for RCDI, but increased knowledge of the intestinal microbiota in health maintenance, as well as controlled trials of FMT in a wide range of disorders are needed before FMT can be accepted and applied clinically.}, }
@article {pmid23034604, year = {2012}, author = {Damman, CJ and Miller, SI and Surawicz, CM and Zisman, TL}, title = {The microbiome and inflammatory bowel disease: is there a therapeutic role for fecal microbiota transplantation?.}, journal = {The American journal of gastroenterology}, volume = {107}, number = {10}, pages = {1452-1459}, doi = {10.1038/ajg.2012.93}, pmid = {23034604}, issn = {1572-0241}, mesh = {Animals ; Disease Models, Animal ; Enema ; Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Genetic Predisposition to Disease ; Humans ; Inflammatory Bowel Diseases/*microbiology/*therapy ; Living Donors ; *Metagenome ; Mice ; Probiotics/*therapeutic use ; Transplantation/methods ; Treatment Outcome ; }, abstract = {One hypothesis for the etiology of inflammatory bowel disease is that an altered or pathogenic microbiota causes inflammation in a genetically susceptible individual. Understanding the microbiota's role in the pathogenesis of the disease could lead to new IBD treatments aimed at shifting the bacteria in the gut back to eubiosis. Probiotics have some efficacy in the treatment of ulcerative colitis (UC), but our current repertoire is limited in potency. Fecal microbiota therapy (FMT) is an emerging treatment for several gastrointestinal and metabolic disorders. It has demonstrated efficacy in treating refractory Clostridium difficile infection, and there are case reports of FMT successfully treating UC. Further clinical studies are justified, and could be complemented by mouse models of fecal transplantation, in which variables can be controlled and manipulated.}, }
@article {pmid23019031, year = {2012}, author = {Zhang, FX and Yang, YB and Ke, GB and Chen, Y and Xu, XM and Tan, ZK and Rong, S}, title = {[Mice cope with parabiosis − assessment of their physiological changes of life].}, journal = {Dong wu xue yan jiu = Zoological research}, volume = {33}, number = {5}, pages = {493-497}, doi = {10.3724/SP.J.1141.2012.05493}, pmid = {23019031}, issn = {0254-5853}, mesh = {Animals ; Body Weight ; Corticosterone/metabolism ; Female ; Male ; Mice/*physiology/surgery ; Mice, Inbred C57BL ; *Models, Animal ; Parabiosis ; }, abstract = {The purpose of this study was to establish a parabiotic mice model and assess the physiological changes of the mice under the parabiotic state. Thirteen pairs of isogenic partners were studied. The model was created by preparing a bridge of skin and subcutaneous tissues between the two mice starting distal of the elbow joint along the humerus along the lateral costal region until the end of the waist line. Physiological, social and affective qualities of life were studied in the mice through behavioural observations for 120 days following the parabiotic surgery. During the first 2-3 days following the operation, the animals suffered from severe pain and distress. During the following days and weeks, the physiological system began to recover and the animals displayed behavioral adaptations to the parabiotic condition. All animals survived at day 120. At three days post operation, the body weight began to decrease. Following this, the animals experienced a continual body weight recovery and reached pre-surgical measures at about 30 days post op. Forty-eight h post op., faecal corticosterone-metabolites were extremely elevated, but their levels returned to two to four times of levels in control females within 72 hours post op. The faecal corticosterone-metabolite levels decreased near to control values on day 75. Out of the 13 pairs, the blood exchange rate of three parabiotic partners was tested, with the result being normal post op. After 12 weeks, the total blood exchange between both partners needed 63 or 46 or 107 min, respectively. These results demonstrated that the animals could adapt behaviourally to the parabiotic situation. Therefore, this parabiosis mouse model may provide useful insights in many research areas, such as transplantation immunity, hematological system and metabolism, etc.}, }
@article {pmid23017673, year = {2013}, author = {Walker, AW and Lawley, TD}, title = {Therapeutic modulation of intestinal dysbiosis.}, journal = {Pharmacological research}, volume = {69}, number = {1}, pages = {75-86}, doi = {10.1016/j.phrs.2012.09.008}, pmid = {23017673}, issn = {1096-1186}, support = {G0901743/MRC_/Medical Research Council/United Kingdom ; 076964/WT_/Wellcome Trust/United Kingdom ; 098051/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Gastrointestinal Diseases/*microbiology ; Humans ; Intestines/*microbiology ; Metagenome/genetics/*physiology ; }, abstract = {The human gastrointestinal tract is home to an extremely numerous and diverse collection of microbes, collectively termed the "intestinal microbiota". This microbiota is considered to play a number of key roles in the maintenance of host health, including aiding digestion of otherwise indigestible dietary compounds, synthesis of vitamins and other beneficial metabolites, immune system regulation and enhanced resistance against colonisation by pathogenic microorganisms. Conversely, the intestinal microbiota is also a potent source of antigens and potentially harmful compounds. In health, humans can therefore be considered to exist in a state of natural balance with their microbial inhabitants. A shift in the balance of microbiota composition such that it may become deleterious to host health is termed "dysbiosis". Dysbiosis of the gut microbiota has been implicated in numerous disorders, ranging from intestinal maladies such as inflammatory bowel diseases and colorectal cancer to disorders with more systemic effects such as diabetes, metabolic syndrome and atopy. Given the far reaching influence of the intestinal microbiota on human health a clear future goal must be to develop reliable means to alter the composition of the microbiota and restore a healthy balance of microbial species. While it is clear that much fundamental research remains to be done, potentially important therapeutic options include narrow spectrum antibiotics, novel probiotics, dietary interventions and more radical techniques such as faecal transplantation, all of which aim to suppress clinical dysbiosis, restore intestinal microbiota diversity and improve host health.}, }
@article {pmid22990849, year = {2012}, author = {Zipursky, JS and Sidorsky, TI and Freedman, CA and Sidorsky, MN and Kirkland, KB}, title = {Patient attitudes toward the use of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {55}, number = {12}, pages = {1652-1658}, doi = {10.1093/cid/cis809}, pmid = {22990849}, issn = {1537-6591}, mesh = {Adolescent ; Adult ; Aged ; Clostridioides difficile/*physiology ; Enterocolitis, Pseudomembranous/epidemiology/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Middle Aged ; Patient Acceptance of Health Care ; Secondary Prevention ; Transplantation/*methods/*psychology ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT), a safe, effective alternative therapy for recurrent Clostridium difficile infection (CDI), is infrequently used, in part because of an assumption that patients are unwilling to consider FMT because of its unappealing nature.<br><br>METHODS: Through a structured survey, including hypothetical case scenarios, we assessed patient perceptions of the aesthetics of FMT and their willingness to consider it as a treatment option, when presented with scenarios involving recurrent CDI.<br><br>RESULTS: Four hundred surveys were distributed; 192 (48%) were returned complete. Seventy percent of respondents were female; 59% were >49 years of age. When provided efficacy data only, 162 respondents (85%) chose to receive FMT, and 29 (15%) chose antibiotics alone. When aware of the fecal nature of FMT, 16 respondents changed their choice from FMT to antibiotics alone, but there was no significant change in the total number choosing FMT (154 [81%]; P = .15). More respondents chose FMT if offered as a pill (90%; P = .002) or if their physician recommended it (94%; P < .001). Respondents rated all aspects of FMT at least "somewhat unappealing," selecting "the need to handle stool" and "receiving FMT by nasogastric tube" as most unappealing. Women rated all aspects of FMT more unappealing; older respondents rated all aspects less unappealing. Most respondents preferred to receive FMT in the hospital (48%) or physician's office (39%); 77% were willing to pay out-of-pocket for FMT.<br><br>CONCLUSIONS: Patients recognize the inherently unappealing nature of FMT, but they are nonetheless open to considering it as a treatment alternative for recurrent CDI, especially when recommended by a physician.}, }
@article {pmid22990845, year = {2012}, author = {Brandt, LJ}, title = {Editorial commentary: fecal microbiota transplantation: patient and physician attitudes.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {55}, number = {12}, pages = {1659-1660}, doi = {10.1093/cid/cis812}, pmid = {22990845}, issn = {1537-6591}, mesh = {Clostridioides difficile/*physiology ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Transplantation/*methods/*psychology ; }, }
@article {pmid22988938, year = {2012}, author = {Motamedi, N and Mairhofer, H and Nitschko, H and Jäger, G and Koszinowski, UH}, title = {The polyomaviruses WUPyV and KIPyV: a retrospective quantitative analysis in patients undergoing hematopoietic stem cell transplantation.}, journal = {Virology journal}, volume = {9}, number = {}, pages = {209}, pmid = {22988938}, issn = {1743-422X}, mesh = {Adult ; Feces/virology ; Female ; Gastrointestinal Diseases/virology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Infant ; Longitudinal Studies ; Male ; Polyomavirus/*classification/*isolation &amp; purification ; Polyomavirus Infections/*virology ; Respiratory Tract Infections/virology ; Retrospective Studies ; Sputum/virology ; Urine/virology ; }, abstract = {BACKGROUND: The polyomaviruses WUPyV and KIPyV have been detected in various sample types including feces indicating pathogenicity in the gastrointestinal (GI) system. However, quantitative viral load data from other simultaneously collected sample types are missing. As a consequence, primary replication in the GI system cannot be differentiated from swallowed virus from the respiratory tract. Here we present a retrospective quantitative longitudinal analysis in simultaneously harvested specimens from different organ sites of patients undergoing hematopoietic stem cell transplantation (HSCT). This allows the definition of sample types where deoxyribonucleic acid (DNA) detection can be expected and, as a consequence, the identification of their primary replication site.<br><br>FINDINGS: Viral DNA loads from 37 patients undergoing HSCT were quantified in respiratory tract secretions (RTS), stool and urine samples as well as in leukocytes (n&#x2009;=&#x2009;449). Leukocyte-associated virus could not be found. WUPyV was found in feces, RTS and urine samples of an infant, while KIPyV was repeatedly detected in RTS and stool samples of 4 adult patients.RTS and stool samples were matched to determine the viral load difference showing a mean difference of 2.3 log copies/ml (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: The data collected in this study suggest that virus detection in the GI tract results from swallowed virus from the respiratory tract (RT). We conclude that shedding from the RT should be ruled out before viral DNA detection in the feces can be correlated to GI symptoms.}, }
@article {pmid22982981, year = {2013}, author = {Agholi, M and Hatam, GR and Motazedian, MH}, title = {Microsporidia and coccidia as causes of persistence diarrhea among liver transplant children: incidence rate and species/genotypes.}, journal = {The Pediatric infectious disease journal}, volume = {32}, number = {2}, pages = {185-187}, doi = {10.1097/INF.0b013e318273d95f}, pmid = {22982981}, issn = {1532-0987}, mesh = {Child ; Child, Preschool ; Coccidia/genetics/*isolation &amp; purification ; Coccidiosis/*parasitology ; DNA, Fungal/analysis ; DNA, Protozoan/analysis ; Diarrhea/*etiology/microbiology/parasitology ; Feces/microbiology/parasitology ; Female ; Genotype ; Humans ; Infant ; *Liver Transplantation ; Male ; Microscopy ; Microsporida/genetics/*isolation &amp; purification ; Microsporidiosis/*microbiology ; Polymerase Chain Reaction ; Prospective Studies ; }, abstract = {We determined species/genotype(s) of enteric microsporidia and coccidia causing diarrhea among 44 liver transplant children in Shiraz Nemazee hospital using acid-fast-trichrome staining and polymerase chain reaction-sequencing techniques. Enterocytozoon bieneusi (genotype D), Cryptosporidium (parvum and meleagridis) were detected in 6.81% and 11.36% of the children, respectively.}, }
@article {pmid22937601, year = {2012}, author = {}, title = {Fecal microbiota transplantation for treating recurrent Clostridium difficile infection.}, journal = {OR manager}, volume = {28}, number = {8}, pages = {15-18}, pmid = {22937601}, issn = {8756-8047}, mesh = {Clostridioides difficile/drug effects/*isolation &amp; purification ; Clostridium Infections/microbiology/prevention &amp; control/*therapy ; Colon/*microbiology ; Feces/*microbiology ; Humans ; *Metagenome ; *Transplantation/economics ; }, }
@article {pmid22926117, year = {2012}, author = {Kim, SW}, title = {[Treatment of refractory or recurrent Clostridium difficile infection].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {60}, number = {2}, pages = {71-78}, doi = {10.4166/kjg.2012.60.2.71}, pmid = {22926117}, issn = {2233-6869}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/immunology/therapeutic use ; Clostridioides difficile/drug effects/pathogenicity ; Enterocolitis, Pseudomembranous/*drug therapy ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Probiotics/therapeutic use ; Recurrence ; Vancomycin/therapeutic use ; }, abstract = {The incidence and severity of Clostridium difficile infection (CDI) has increased over the past decades. It is related to the emergence of hypervirulent strains and increased use of antibiotics. The incidence of refractory CDI to standard therapies and the risk for recurrent CDI are also increasing. Current guidelines recommend the first recurrence to be treated with the same agent used for the initial episode. However, data are lacking to support any particular treatment strategy for severe refractory CDI or cases with multiple recurrence. Treatments currently available for CDI are inadequate to prevent recurrence. Widely used method for managing a subsequent recurrence involves tapering followed by pulsed doses of vancomycin. Other potentially effective strategies for recurrent CDI are use of other antibiotics such as fidaxomicin, nitazoxanide, rifaximin, tigecycline, and teicoplanin. There are efforts to recover gut microflora and to optimize immune response to CDI. These include use of probiotics, fecal microbiota transplantation, intravenous immunoglobulin, monoclonal antibodies directed against C. difficile toxins, and active vaccination. However treatment of patients with refractory CDI and those with multiple CDI recurrences is based on limited clinical evidence, and there is an ongoing need for continued research to improve the outcomes these patients.}, }
@article {pmid22907591, year = {2012}, author = {Jarzembowski, T and Daca, A and Bryl, E and Wiśniewska, K and Gołębiewska, J and Dębska-Ślizień, A and Rutkowski, B and Witkowski, J}, title = {Increased pheromone cCF10 expression in Enterococcus faecalis biofilm formed by isolates from renal transplant patients.}, journal = {Current microbiology}, volume = {65}, number = {6}, pages = {656-659}, pmid = {22907591}, issn = {1432-0991}, mesh = {Bacterial Proteins/genetics/metabolism ; Biofilms/*growth &amp; development ; Enterococcus faecalis/isolation &amp; purification/metabolism/*pathogenicity ; Feces/microbiology ; Flow Cytometry ; *Gene Expression Regulation, Bacterial ; Glucose 1-Dehydrogenase/genetics/metabolism ; Gram-Positive Bacterial Infections/*diagnosis/microbiology ; Humans ; In Situ Hybridization, Fluorescence/*methods ; *Kidney Transplantation ; Oligopeptides/genetics/*metabolism ; Pheromones/genetics/*metabolism ; Urine/microbiology ; Virulence ; }, abstract = {Renal transplant recipients are at a high risk of developing infectious complications even caused by commensal bacteria. This is because of various physiological non-immunological, and immunological protective mechanisms are not fully efficient in RTx patients. Therefore, rapid and precise diagnostic tools are essential in this particular group of patients. We aimed to develop simple and sensitive protocol Flow-Fish for the study of gene expression in enterococci and to compare expression of genes involved in virulence regulation in biofilm and planktonic form of Enterococcus faecalis. Proper optimization of the method was demonstrated with analysis of dehydrogenase gene expression. According to expectation reduction of the dehydrogenase gene expression was observed in biofilm. Furthermore, expression of studied gene was higher in clinical than in commensal strains. We have also found that in contrast to dehydrogenase gene, pheromone cCF10 gene expression increasing then clinical strains formed biofilm.}, }
@article {pmid22898758, year = {2013}, author = {Chandra, A and Gupta, V and Kumar, M and Parihar, A and Kumar, A and Jauhari, R and Singh, D and Shrivastav, PK and Kumar, P}, title = {Anatomical basis of antropyloric transposition for fecal incontinence in humans: the infrapyloric approach.}, journal = {Surgical and radiologic anatomy : SRA}, volume = {35}, number = {1}, pages = {67-74}, pmid = {22898758}, issn = {1279-8517}, mesh = {Adult ; Aged ; Angiography/methods ; Fecal Incontinence/physiopathology/*surgery ; Female ; Gastroepiploic Artery/*diagnostic imaging ; Graft Rejection ; Graft Survival ; Humans ; Male ; Middle Aged ; Pancreaticoduodenectomy/methods ; Perineum/*surgery ; Pylorus/blood supply/diagnostic imaging/*transplantation ; Plastic Surgery Procedures/methods ; Tomography, X-Ray Computed/methods ; Treatment Outcome ; }, abstract = {PURPOSE: Antropylorus transposition in the perineum for end-stage anal incontinence has shown to be feasible in humans. Vascular anatomy of the antro-pyloro-duodenal area is critical in preventing complications and increasing pyloric graft survival. This study was undertaken to examine the vascular anatomy of antro-pyloro-duodenal area in an attempt to safeguard the graft blood supply and improve its survival.<br><br>METHODS: After obtaining preoperative CT angiography to delineate the infrapyloric artery (IP a.), bench dissection of resected pancreaticoduodenectomy specimens was performed in 12 patients. Ex vivo angiography of these specimens were also performed. Subsequent to the information obtained from these dissections, the method of antropylorus mobilization during transposition was modified in terms of the site of division of the right gastroepiploic a. (Rt GEA). Perioperative outcomes (graft related complications, fecal incontinence scores, Doppler flow studies, and manometry studies of the graft) were compared between the two groups.<br><br>RESULTS: IP a. originated only from the Rt GEA in 8 cases (66&#xa0;%) and from both the gastroduodenal a. and the Rt GEA in the rest. However, its origin solely from the gastroduodenal a. was not observed. The pyloric graft survival, pyloric valve pressures and Doppler flow velocities were significantly (p&#xa0;<&#xa0;0.05) better when the infrapyloric a. was preserved following this refinement. However, no immediate significant difference in incontinence scores was observed.<br><br>CONCLUSIONS: Careful preservation of the pyloric valve vascularity by preserving the IP a. by dividing the Rt GEA at its origin increases vascularity, survival and contractility of the pyloric graft in perineum.}, }
@article {pmid22897737, year = {2013}, author = {Kessler, DA and Shi, PA and Avecilla, ST and Shaz, BH}, title = {Results of lookback for Chagas disease since the inception of donor screening at New York Blood Center.}, journal = {Transfusion}, volume = {53}, number = {5}, pages = {1083-1087}, doi = {10.1111/j.1537-2995.2012.03856.x}, pmid = {22897737}, issn = {1537-2995}, mesh = {Aged ; Antibodies, Protozoan/*blood ; Blood Banking/*methods ; Blood Safety/*methods ; Chagas Disease/diagnosis/prevention &amp; control/*transmission ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; New York City ; *Platelet Transfusion ; Trypanosoma cruzi/*immunology ; }, abstract = {BACKGROUND: Chagas disease is a parasitic infection by Trypanosoma cruzi, typically transmitted via infected triatomine bug fecal contamination of bite sites. Other routes of infection include congenital, oral, organ transplantation, and blood product transmission.<br><br>STUDY DESIGN AND METHODS: From 2007 until 2011, New York Blood Center screened donations for the presence of T. cruzi antibodies using a Food and Drug Administration-approved test. Confirmatory testing was performed and recipients of units donated by confirmed-positive donors were investigated via lookback.<br><br>RESULTS: A total of 204 donors were T. cruzi antibody positive representing 0.019% of all donors during this time period (1,066,516 unique donors screened). Of the enzyme-linked immunosorbent assay-reactive donors, 77 were confirmed positive by radioimmunoprecipitation assay (0.007%). At least 154 units from 29 of the confirmed-positive donors had been transfused to 141 recipients. At the time of lookback, 48 of the 141 recipients were alive and seven underwent T. cruzi screening. Two recipients were found to be immunofluorescence assay (IFA) positive. Both IFA-positive recipients received a leukoreduced apheresis platelet unit (two separate donations) from the same confirmed positive donor, a 72-year-old immigrant from Argentina.<br><br>CONCLUSIONS: Lookback analysis was able to identify the first two cases of probable transfusion-transmitted T. cruzi infection since implementation of the national screening program, which increases the total number of reported cases in the United States to 8.}, }
@article {pmid22885333, year = {2012}, author = {Desreumaux, P and Foussat, A and Allez, M and Beaugerie, L and Hébuterne, X and Bouhnik, Y and Nachury, M and Brun, V and Bastian, H and Belmonte, N and Ticchioni, M and Duchange, A and Morel-Mandrino, P and Neveu, V and Clerget-Chossat, N and Forte, M and Colombel, JF}, title = {Safety and efficacy of antigen-specific regulatory T-cell therapy for patients with refractory Crohn's disease.}, journal = {Gastroenterology}, volume = {143}, number = {5}, pages = {1207-1217.e2}, doi = {10.1053/j.gastro.2012.07.116}, pmid = {22885333}, issn = {1528-0012}, mesh = {Adult ; Aged ; C-Reactive Protein/metabolism ; Crohn Disease/blood/*therapy ; Feces ; Female ; Humans ; *Immunotherapy/adverse effects ; Leukocyte L1 Antigen Complex/metabolism ; Lymphocyte Count ; Male ; Middle Aged ; Ovalbumin/immunology ; Quality of Life ; Severity of Illness Index ; Surveys and Questionnaires ; T-Lymphocytes, Regulatory/immunology/*transplantation ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: New therapeutic strategies are needed for patients with refractory Crohn's disease (CD). We evaluated data from the Crohn's And Treg Cells Study (CATS1) to determine the safety and efficacy of antigen-specific T-regulatory (Treg) cells for treatment of patients with refractory CD.<br><br>METHODS: We performed a 12-week, open-label, multicenter, single-injection, escalating-dose, phase 1/2a clinical study in 20 patients with refractory CD. Ovalbumin-specific Treg cells (ova-Tregs) were isolated from patients' peripheral blood mononuclear cells (PBMCs), exposed to ovalbumin, and administrated intravenously. Safety and efficacy were assessed using clinical and laboratory parameters. We evaluated proliferation of PBMCs in response to ovalbumin.<br><br>RESULTS: Injections of ova-Tregs were well tolerated, with 54 adverse events (2 related to the test reagent) and 11 serious adverse events (3 related to the test reagent, all recovered). Overall, a response, based on a reduction in Crohn's Disease Activity Index (CDAI) of 100 points, was observed in 40% of patients at weeks 5 and 8. Six of the 8 patients (75%) who received doses of 10(6) cells had a response at weeks 5 and 8, with a statistically significant reduction in CDAI. In this group, remission (based on CDAI &#x2264;150) was observed in 3 of 8 patients (38%) at week 5 and 2 of 8 patients (25%) at week 8.<br><br>CONCLUSIONS: Administration of antigen-specific Tregs to patients with refractory CD (CATS1) was well tolerated and had dose-related efficacy. The ovalbumin-specific immune response correlated with clinical response, supporting immune-suppressive mechanisms of ova-Tregs. The consistency of results among different assessment methods supports the efficacy of ova-Tregs; this immune therapy approach warrants further clinical and mechanistic studies in refractory CD. Eudract, Number: 2006-004712-44.}, }
@article {pmid22882913, year = {2012}, author = {Li, H and Yu, DL and Ren, L and Zhong, L and Peng, ZH and Teng, MJ}, title = {Analysis of Gram-positive bacterial infection in patients following liver transplantation.}, journal = {Chinese medical journal}, volume = {125}, number = {14}, pages = {2417-2421}, pmid = {22882913}, issn = {2542-5641}, mesh = {Adult ; Anti-Bacterial Agents/pharmacology ; Drug Resistance, Multiple, Bacterial/genetics ; Female ; Gram-Positive Bacteria/drug effects/genetics/pathogenicity ; Gram-Positive Bacterial Infections/*epidemiology/etiology/microbiology ; Humans ; Liver Transplantation/*adverse effects ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Molecular Epidemiology ; }, abstract = {BACKGROUND: Liver transplantation is the most effective treatment for patients with end-stage liver failure, however infection after transplantation is a serious clinical complication. The purpose of this research was to investigate the molecular epidemiology and the influence of multidrug-resistant Gram-positive infection in patients, following liver transplantation, to provide reference for clinical treatment and prevention of Gram-positive bacterial infection.<br><br>METHODS: We isolated and detected bacteria from phlegm, throat swabs, urine, wound or wound secretions, blood, and fecal samples from 221 liver transplant patients in our hospital from January 2007 to April 2010. All isolated bacterial strains were identified and tested by minimal inhibitory concentration (MIC) drug-sensitive detection using the BioMerieux ATB bacterial identification instrument and repetitive extragenic palindromic-polymerase chain reaction (REP-PCR) detection of bacterial homology. Risk factors were calculated by multivariate Logistic regression analysis.<br><br>RESULTS: We collected 250 specimens from 221 patients hospitalized following liver transplantation surgery, of which 29 patients developed multiple infections. Sixty-five Gram-positive bacterial strains were isolated from different specimens from 53 infectious patients. We detected 29 multidrug-resistant Gram-positive strains from 29 patients (44.62%), including 20 Staphylococcus aureus (S. aureus) strains (68.97%) and nine Enterococcus strains (31.03%). All 20 S. aureus strains were highly resistant to aminoglycosides (gentamicin), cephalosporins (cefoxitin), quinolones (ciprofloxacin and levofloxacin), lincomycins (clindamycin), penicillin, and erythromycin. The resistance rate reached 100% in some cases. The S. aureus strains were highly sensitive to vancomycin and oxazolidinone (linezolid), with MIC50 < 2 &#xb5;g/ml for both. The nine Enterococci strains were also highly resistant to aminoglycosides, quinolones, and penicillins, and highly sensitive to vancomycin (MIC50 < 2 &#xb5;g/ml) and oxazolidinone (MIC50 < 1 &#xb5;g/ml). Using REP-PCR detection, S. aureus was divided into five genotypes with 14 B-type strains. Enterococcus was divided into 11 genotypes, with two D-type strains, two G-type strains, and two K-type strains. The risk factors for Gram-positive bacterial infection in patients following liver transplantation were preoperative use of antibiotics (OR = 3.949, P = 0.004), high intra-operative blood input (OR = 1.071, P = 0.005), and postoperative renal failure (OR = 5.427, P = 0.043).<br><br>CONCLUSIONS: S. aureus and Enterococcus were the main pathogens causing infection following liver transplantation in patients with drug-resistant Gram-positive bacterial infection. The isolated strains were resistant to multiple antibiotics. B-type S. aureus strains were predominant. Reasonable use of antibiotics, decreasing intra-operative blood input, and preventing post-operative renal failure may reduce Gram-positive bacterial infections and the appearance of drug-resistant strains following liver transplantation.}, }
@article {pmid22874805, year = {2012}, author = {Floch, MH}, title = {The power of poop: probiotics and fecal microbial transplant.}, journal = {Journal of clinical gastroenterology}, volume = {46}, number = {8}, pages = {625-626}, doi = {10.1097/MCG.0b013e3182667a93}, pmid = {22874805}, issn = {1539-2031}, mesh = {*Clostridioides difficile ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Probiotics/*therapeutic use ; Transplantation/*methods ; Treatment Outcome ; }, }
@article {pmid22847629, year = {2012}, author = {Postigo, R and Kim, JH}, title = {Colonoscopic versus nasogastric fecal transplantation for the treatment of Clostridium difficile infection: a review and pooled analysis.}, journal = {Infection}, volume = {40}, number = {6}, pages = {643-648}, pmid = {22847629}, issn = {1439-0973}, mesh = {Clostridioides difficile/*pathogenicity ; Colonoscopy/*methods ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Humans ; Intubation, Gastrointestinal/*methods ; Therapeutic Irrigation/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been demonstrated to be highly effective for the treatment of recurrent Clostridium difficile infection (CDI). However, the best route of administration has not been established. We present a pooled analysis of the reported cases of CDI treated with FMT via colonoscopy or nasogastric tube (NGT) to evaluate treatment efficacy.<br><br>METHODS: PubMed was searched for English-written articles published up to December 2011. Studies that reported cases of FMT for recurrent CDI using either colonoscopy or NGT-guided fecal infusion were reviewed.<br><br>RESULTS: A total of 182 patients from 12 published studies were identified; 148 patients received FMT via colonoscopy (colonoscopy group) and 34 patients received FMT via NGT (NGT group). The median age in the colonoscopy group as compared with the NGT group was 72 and 82 years, respectively. There were differences regarding pre-FMT treatment for CDI; 134 patients (90.5 %, 134/148) received lavage with/without antibiotic in the colonoscopy group and 34 patients (100.0 %, 34/34) received antibiotic without lavage in the NGT group, P < 0.001. A higher stool volume was used for FMT in the colonoscopy group (121 patients, 81.8 %, used 100-400 ml) than in the NGT group (33 patients, 97.0 %, used <100 ml), P < 0.001. The treatment efficacy did not differ significantly; 93.2 % (138/148) success for the colonoscopy group as compared to 85.3 % success (29/34) for the NGT group, P = 0.162. Recurrence of CDI after FMT was also similar in both the colonoscopy group (8/148 5.4 %) versus the NGT group (2/34, 5.9 %), P = 1.000.<br><br>CONCLUSIONS: Despite procedural differences, FMT via colonoscopy or NGT appears to be highly effective and safe for the management of recurrent CDI.}, }
@article {pmid22833618, year = {2012}, author = {Collins, MG and Teo, E and Cole, SR and Chan, CY and McDonald, SP and Russ, GR and Young, GP and Bampton, PA and Coates, PT}, title = {Screening for colorectal cancer and advanced colorectal neoplasia in kidney transplant recipients: cross sectional prevalence and diagnostic accuracy study of faecal immunochemical testing for haemoglobin and colonoscopy.}, journal = {BMJ (Clinical research ed.)}, volume = {345}, number = {}, pages = {e4657}, pmid = {22833618}, issn = {1756-1833}, mesh = {Adenoma/diagnosis/*epidemiology/pathology ; Colonoscopy ; Colorectal Neoplasms/diagnosis/*epidemiology/pathology ; Cross-Sectional Studies ; Feces/chemistry ; Female ; Gastrointestinal Hemorrhage/epidemiology ; Hemoglobins ; Humans ; Kidney Failure, Chronic/*epidemiology/surgery ; Kidney Transplantation/*statistics &amp; numerical data ; Logistic Models ; Male ; Mass Screening/*methods ; Middle Aged ; Neoplasm Staging ; *Occult Blood ; Prevalence ; Rectum ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: To investigate whether screening kidney transplant recipients aged over 50 years for colorectal cancer with a faecal immunochemical test for haemoglobin might be justified, by determining the prevalence of advanced colorectal neoplasia and evaluating the diagnostic accuracy of faecal haemoglobin testing compared with colonoscopy in a population of kidney transplant recipients at otherwise average risk.<br><br>DESIGN: Cross sectional prevalence and diagnostic accuracy study with index test of faecal haemoglobin and reference standard of colonoscopy.<br><br>SETTING: Outpatient clinics in metropolitan and regional hospitals in South Australia.<br><br>PARTICIPANTS: 229 kidney transplant recipients aged 50 years and over, who were at least 6 months (mean 9.0 (SD 8.4) years) post-transplant and otherwise at average risk of colorectal cancer, completed the study between June 2008 and October 2011.<br><br>INTERVENTIONS: Faecal immunochemical testing (Enterix Insure) for human haemoglobin, followed by colonoscopy with histological evaluation of retrieved samples.<br><br>MAIN OUTCOME MEASURES: Prevalence of advanced colorectal neoplasia, defined as an adenoma at least 10 mm in diameter, villous features, high grade dysplasia, or colorectal cancer; sensitivity, specificity, and predictive values of faecal haemoglobin testing for advanced neoplasia compared with colonoscopy.<br><br>RESULTS: Advanced colorectal neoplasia was found in 29 (13%, 95% confidence interval 9% to 18%) participants, including 2% (n=4) with high grade dysplasia and 2% (n=5) with colorectal cancer. Faecal testing for haemoglobin was positive in 12% (n=28); sensitivity, specificity, and positive and negative predictive values for advanced neoplasia were 31.0% (15.3% to 50.8%), 90.5% (85.6% to 94.2%), 32.1% (15.9% to 52.4%), and 90.1% (85.1% to 93.8%). Colonoscopy was well tolerated, with no significant adverse outcomes. To identify one case of advanced neoplasia, 8 (6 to 12) colonoscopies were needed.<br><br>CONCLUSIONS: Kidney transplant recipients aged over 50 years have a high prevalence of advanced colorectal neoplasia. Faecal haemoglobin screening for colorectal neoplasia has similar performance characteristics in transplant recipients to those reported in general population studies, with poor sensitivity but reasonable specificity. Surveillance colonoscopy might be a more appropriate approach in this population.<br><br>TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12608000154303.}, }
@article {pmid22827693, year = {2012}, author = {Anderson, JL and Edney, RJ and Whelan, K}, title = {Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {36}, number = {6}, pages = {503-516}, doi = {10.1111/j.1365-2036.2012.05220.x}, pmid = {22827693}, issn = {1365-2036}, mesh = {Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; *Metagenome ; Microbial Interactions ; Randomized Controlled Trials as Topic ; Transplantation/methods ; }, abstract = {BACKGROUND: The intestinal microbiota is involved in the pathogenesis of inflammatory bowel disease (IBD). Faecal microbiota transplantation (FMT) has been used for the management of IBD as well as infectious diarrhoea.<br><br>AIM: To undertake a systematic review of FMT in patients with IBD.<br><br>METHODS: The systematic review followed Cochrane and PRISMA recommendations. Nine electronic databases were searched in addition to hand searching and contacting experts. Inclusion criteria were reports (RCT, nonrandomised trials, case series and case reports) of FMT in patients with IBD.<br><br>RESULTS: Of the 5320 articles identified, 17 fulfilled the inclusion criteria, none of which were controlled trials. There were nine case series/case reports of patients receiving FMT for management of their IBD, and eight where FMT was for the treatment of infectious diarrhoea in IBD. These 17 articles reported on 41 patients with IBD (27 UC, 12 Crohn's, 2 unclassified) with a follow-up period of between 2 weeks and 13 years. Where reported, FMT was administered via colonoscopy/enema (26/33) or via enteral tube (7/33). In patients treated for their IBD, the majority experienced a reduction of symptoms (19/25), cessation of IBD medications (13/17) and disease remission (15/24). There was resolution of C. difficile infection in all those treated for such (15/15).<br><br>CONCLUSIONS: Whilst the available evidence is limited and weak, it suggests that faecal microbiota transplantation has the potential to be an effective and safe treatment for IBD, at least when standard treatments have failed. Well-designed randomised controlled trials are required to investigate these findings.}, }
@article {pmid22804692, year = {2012}, author = {Campbell, JP and Mackenzie, MJ and Yentis, SM and Sooranna, SR and Johnson, MR}, title = {An evaluation of the ability of leucocyte depletion filters to remove components of amniotic fluid.}, journal = {Anaesthesia}, volume = {67}, number = {10}, pages = {1152-1157}, doi = {10.1111/j.1365-2044.2012.07247.x}, pmid = {22804692}, issn = {1365-2044}, mesh = {Adult ; Amniotic Fluid/chemistry/*cytology ; Cesarean Section ; Cytological Techniques/*economics/*methods ; Developing Countries ; Endothelin-1/analysis ; Female ; Fetomaternal Transfusion/therapy ; Filtration/*methods ; Hair ; Humans ; Infant, Newborn ; Leukocytes/*physiology ; Meconium/chemistry ; Monitoring, Intraoperative ; Operative Blood Salvage/*methods ; Pregnancy ; Thromboplastin/analysis ; Vernix Caseosa/chemistry ; alpha-Fetoproteins/analysis ; }, abstract = {Haemorrhage remains an important cause of maternal mortality worldwide. Cell salvage carries a theoretical risk of amniotic fluid embolus syndrome and is too expensive for use in many parts of the world. To explore cheaper options, we investigated whether a leucocyte depletion filter alone removes components of pure amniotic fluid. Amniotic fluid was collected from 10 women during elective caesarean section and passed through a LeukoGuard® RS filter. Pre- and post-filtration samples were compared in the laboratory. Lamellar bodies and fetal squames were almost completely removed (filtration efficacy 96.6% and 99.9%, respectively; p<0.0001 and <0.0004), and hair was completely removed (p=0.002). Filtration had no effect on concentrations of α-fetoprotein, tissue factor or endothelin-1, or on the presence of meconium or vernix. Additional work is required to evaluate whether cell salvage using filtration alone may be useful in maternal haemorrhage in the developing world.}, }
@article {pmid22738211, year = {2012}, author = {Hoerning, A and Hegen, B and Wingen, AM and Cetiner, M and Lainka, E and Kathemann, S and Fiedler, M and Timm, J and Wenzel, JJ and Hoyer, PF and Gerner, P}, title = {Prevalence of hepatitis E virus infection in pediatric solid organ transplant recipients--a single-center experience.}, journal = {Pediatric transplantation}, volume = {16}, number = {7}, pages = {742-747}, doi = {10.1111/j.1399-3046.2012.01740.x}, pmid = {22738211}, issn = {1399-3046}, mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Hepatitis E/complications/*epidemiology ; Hepatitis E virus/*metabolism ; Humans ; Immunoglobulin G/chemistry ; Immunosuppression Therapy ; Infant ; Kidney Transplantation/*methods ; Liver Transplantation/*methods ; Male ; Prevalence ; RNA, Viral/metabolism ; Seroepidemiologic Studies ; Transplantation/*adverse effects ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {HEV infection appears to be an emerging disease in industrialized countries. The aim of this study was to evaluate the prevalence of HEV infection in pediatric solid organ transplant recipients. One hundred and twenty-four pediatric recipients of liver (n = 41) or kidney (n = 83) transplants aged between one and 18 yr were screened for anti-HEV IgG antibodies. Patients were tested for fecal HEV RNA excretion if they showed anti-HEV seropositivity. As a control group, 108 immunocompetent pediatric patients without liver disease aged between three and 18 yr were screened for anti-HEV IgG. HEV seroprevalence was 2.4% in renal Tx (2/83), 4.9% in liver Tx patients (2/41), and 3.2% overall (4/124). Three of these four patients were HEV RNA-negative. In one renal transplant patient, HEV genotype 3 RNA excretion persisted and liver enzymes were elevated, indicating chronic hepatitis. In the control group, eight patients (7.4%) were HEV IgG-positive without biochemical evidence of hepatitis. The prevalence of HEV infection in pediatric renal or liver transplant recipients is not higher compared with immunocompetent children. Chronic HEV infection with long-term carriage of the virus may develop in pediatric transplant recipients. Autochthonous HEV infection needs to be considered in uncertain cases of hepatitis in immunosuppressed as well as immunocompetent children.}, }
@article {pmid22732575, year = {2012}, author = {El-Matary, W and Simpson, R and Ricketts-Burns, N}, title = {Fecal microbiota transplantation: are we opening a can of worms?.}, journal = {Gastroenterology}, volume = {143}, number = {2}, pages = {e19; author reply e19-20}, doi = {10.1053/j.gastro.2012.04.055}, pmid = {22732575}, issn = {1528-0012}, mesh = {Clostridioides difficile/*pathogenicity ; *Colonoscopy ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; }, }
@article {pmid22718773, year = {2012}, author = {Taur, Y and Xavier, JB and Lipuma, L and Ubeda, C and Goldberg, J and Gobourne, A and Lee, YJ and Dubin, KA and Socci, ND and Viale, A and Perales, MA and Jenq, RR and van den Brink, MR and Pamer, EG}, title = {Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {55}, number = {7}, pages = {905-914}, pmid = {22718773}, issn = {1537-6591}, support = {1R01 AI42135/AI/NIAID NIH HHS/United States ; 1K23 AI095398-01/AI/NIAID NIH HHS/United States ; K23 AI095398/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; DP2 OD008440/OD/NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; T32 GM007739/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteremia/*epidemiology/*microbiology ; Biodiversity ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Feces/microbiology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Bacteremia is a frequent complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unclear whether changes in the intestinal microbiota during allo-HSCT contribute to the development of bacteremia. We examined the microbiota of patients undergoing allo-HSCT, and correlated microbial shifts with the risk of bacteremia.<br><br>METHODS: Fecal specimens were collected longitudinally from 94 patients undergoing allo-HSCT, from before transplant until 35 days after transplant. The intestinal microbiota was characterized by 454 pyrosequencing of the V1-V3 region of bacterial 16S ribosomal RNA genes. Microbial diversity was estimated by grouping sequences into operational taxonomic units and calculating the Shannon diversity index. Phylogenetic classification was obtained using the Ribosomal Database Project classifier. Associations of the microbiota with clinical predictors and outcomes were evaluated.<br><br>RESULTS: During allo-HSCT, patients developed reduced diversity, with marked shifts in bacterial populations inhabiting the gut. Intestinal domination, defined as occupation of at least 30% of the microbiota by a single predominating bacterial taxon, occurred frequently. Commonly encountered dominating organisms included Enterococcus, Streptococcus, and various Proteobacteria. Enterococcal domination was increased 3-fold by metronidazole administration, whereas domination by Proteobacteria was reduced 10-fold by fluoroquinolone administration. As a predictor of outcomes, enterococcal domination increased the risk of Vancomycin-resistant Enterococcus bacteremia 9-fold, and proteobacterial domination increased the risk of gram-negative rod bacteremia 5-fold.<br><br>CONCLUSIONS: During allo-HSCT, the diversity and stability of the intestinal flora are disrupted, resulting in domination by bacteria associated with subsequent bacteremia. Assessment of fecal microbiota identifies patients at highest risk for bloodstream infection during allo-HCST.}, }
@article {pmid22702052, year = {2012}, author = {Kong, F and Li, F and Liu, J and Chen, Y and Wu, Y and Yang, X and Xiang, B}, title = {[Gluteus maximus transplantation for fecal incontinence after surgery of high anal atresia].}, journal = {Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery}, volume = {26}, number = {5}, pages = {571-575}, pmid = {22702052}, issn = {1002-1892}, mesh = {Adolescent ; Anal Canal/physiopathology/*surgery ; Anus, Imperforate/physiopathology/*surgery ; Buttocks/surgery ; Child ; Child, Preschool ; Fecal Incontinence/etiology/physiopathology/*surgery ; Female ; Humans ; Male ; Muscle Contraction/physiology ; Quality of Life ; Plastic Surgery Procedures/*methods ; Rectum/physiopathology/surgery ; *Surgical Flaps ; Surveys and Questionnaires ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: To investigate the application of gluteus maximus transplantation for fecal incontinence after surgery of high anal atresia.<br><br>METHODS: Between December 2002 and November 2010, 25 patients with fecal incontinence were treated with gluteus maximus transplantation, which was caused by surgery of high anal atresia. There were 11 males and 14 females with an average age of 10.2 years (range, 3-22 years). Preoperative radiography, anorectal manometer, and electromyogram showed abnormality or deficiency of anal sphincter function. Wexner score, Fecal Incontinence Quality of Life (FIQL) questionnaire, and Self-rated Health Measurement Scale Version 1.0 (SRHMS) score were used to evaluate life quality of the patients. The anorectal manometer, intra-rectal ultrasound examination, and defecation radiography were performed.<br><br>RESULTS: Healing of incision by first intention was achieved in 23 cases and rectal-wound fistula occurred in 2 cases. The follow-up time was 1 to 9 years (mean, 6.3 years). Defecation frequency was decreased from more than 10 times to 4-6 times every day. Wexner score and SRHMS were significantly improved at 1 or 2 years after surgery when compared with preoperative socres (P < 0.05). FIQL was also significantly improved after 2 years (P < 0.05). At 2 years after surgery, the anal maximum systolic pressure, contraction duration, and maximum systolic volume were improved, showing significant differences when compared with those at preoperation and 1 year after surgery (P < 0.05).<br><br>CONCLUSION: Gluteus maximus transplantation can improve defecation controls in the patients with fecal incontinence after surgery of high anal atresia.}, }
@article {pmid22675283, year = {2012}, author = {Brandt, LJ}, title = {Fecal transplantation for the treatment of Clostridium difficile infection.}, journal = {Gastroenterology &amp; hepatology}, volume = {8}, number = {3}, pages = {191-194}, pmid = {22675283}, issn = {1554-7914}, }
@article {pmid22674556, year = {2012}, author = {Holmes, E and Kinross, J and Gibson, GR and Burcelin, R and Jia, W and Pettersson, S and Nicholson, JK}, title = {Therapeutic modulation of microbiota-host metabolic interactions.}, journal = {Science translational medicine}, volume = {4}, number = {137}, pages = {137rv6}, doi = {10.1126/scitranslmed.3004244}, pmid = {22674556}, issn = {1946-6242}, support = {R01AA020212/AA/NIAAA NIH HHS/United States ; //Biotechnology and Biological Sciences Research Council/United Kingdom ; //Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {The complex metabolic relationships between the host and its microbiota change throughout life and vary extensively between individuals, affecting disease risk factors and therapeutic responses through drug metabolism. Elucidating the biochemical mechanisms underlying this human supraorganism symbiosis is yielding new therapeutic insights to improve human health, treat disease, and potentially modify human disease risk factors. Therapeutic options include targeting drugs to microbial genes or co-regulated host pathways and modifying the gut microbiota through diet, probiotic and prebiotic interventions, bariatric surgery, fecal transplants, or ecological engineering. The age-associated co-development of the host and its microbiota provides a series of windows for therapeutic intervention from early life through old age.}, }
@article {pmid22674555, year = {2012}, author = {Lemon, KP and Armitage, GC and Relman, DA and Fischbach, MA}, title = {Microbiota-targeted therapies: an ecological perspective.}, journal = {Science translational medicine}, volume = {4}, number = {137}, pages = {137rv5}, pmid = {22674555}, issn = {1946-6242}, support = {DP2 OD007290/OD/NIH HHS/United States ; DP1 OD000964/OD/NIH HHS/United States ; DE020751/DE/NIDCR NIH HHS/United States ; DP1OD000964/OD/NIH HHS/United States ; P30 DE020751/DE/NIDCR NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Humans ; Metagenome/drug effects/*physiology ; Probiotics/therapeutic use ; }, abstract = {The connection between disease and the disruption of homeostatic interactions between the host and its microbiota is now well established. Drug developers and clinicians are starting to rely more heavily on therapies that directly target the microbiota and on the ecology of the microbiota to understand the outcomes of these treatments. The effects of those microbiota-targeted therapies that alter community composition range in scale from eliminating individual strains of a single species (for example, with antibacterial conjugate vaccines) to replacing the entire community with a new intact microbiota (for example, by fecal transplantation). Secondary infections linked to antibiotic use provide a cautionary tale of the unintended consequences of perturbing a microbial species network and highlight the need for new narrow-spectrum antibiotics with rapid companion diagnostics. Insights into microbial ecology will also benefit the development of probiotics, whose therapeutic prospects will depend on rigorous clinical testing. Future probiotics may take the form of a consortium of long-term community residents: "a fecal transplant in a capsule." The efficacy of microbiota-targeted therapies will need to be assessed using new diagnostic tools that measure community function rather than composition, including the temporal response of a microbial community to a defined perturbation such as an antibiotic or probiotic.}, }
@article {pmid22649279, year = {2012}, author = {Neri, F and Cavallari, G and Tsivian, M and Bianchi, E and Aldini, R and Cevenini, M and Guidetti, E and Piras, GL and Pariali, M and Nardo, B}, title = {Effect of colic vein ligature in rats with loperamide-induced constipation.}, journal = {Journal of biomedicine &amp; biotechnology}, volume = {2012}, number = {}, pages = {896162}, pmid = {22649279}, issn = {1110-7251}, mesh = {Animals ; Colon/*blood supply/cytology/surgery ; Constipation/chemically induced/*surgery ; Disease Models, Animal ; Histocytochemistry ; Intestinal Mucosa/chemistry/cytology ; Ligation/*methods ; *Loperamide ; Male ; Rats ; Rats, Sprague-Dawley ; Veins/surgery ; }, abstract = {INTRODUCTION: Medical treatment in chronic constipation is not always successful. Surgery is indicated in unresponsive selected severe cases. This study presents the distal venous colic ligation in rat as a novel surgical approach.<br><br>MATERIALS AND METHODS: 16 rats (study group) were evaluated in 3 phases of 6 days each: A (normal conditions), B (loperamide-induced constipation), and C (colic vein legation) and compared with rats treated in phase C with PEG 4,000 (control group). Blood biochemical and physiological parameters, daily fecal water content (FWC), and histological analysis were performed in all study phases.<br><br>RESULTS: No biochemical and physiological parameters changes were observed. FWC decreased in phase B and increased in phase C in both groups with a grow up to 2.3-fold in study group compared to control (P < 0.0001). Moreover, in study group, a high number of colonic goblet cells were detected (phase C versus phase B: P < 0.001) while no differences were registered in control.<br><br>CONCLUSION: By ligature of the colic vein in constipated rats, an increase in FWC and goblet cells higher than in PEG treated rats was detected. The described surgical procedure appeared effective, simple, and safe; further studies in animal models, however, are necessary to assess its clinical applicability.}, }
@article {pmid22636832, year = {2012}, author = {Stollman, N and Surawicz, C}, title = {Fecal transplant for Clostridium difficile.}, journal = {Archives of internal medicine}, volume = {172}, number = {10}, pages = {825; author reply 825-6}, doi = {10.1001/archinternmed.2012.1055}, pmid = {22636832}, issn = {1538-3679}, mesh = {*Clostridioides difficile ; Enema/*methods ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; }, }
@article {pmid22608365, year = {2012}, author = {Berciaud, S and Rayne, F and Kassab, S and Jubert, C and Faure-Della Corte, M and Salin, F and Wodrich, H and Lafon, ME and , }, title = {Adenovirus infections in Bordeaux University Hospital 2008-2010: clinical and virological features.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {54}, number = {4}, pages = {302-307}, doi = {10.1016/j.jcv.2012.04.009}, pmid = {22608365}, issn = {1873-5967}, mesh = {Adenovirus Infections, Human/*epidemiology/*physiopathology/virology ; Adenoviruses, Human/classification/*genetics/pathogenicity ; Adult ; Child ; Coinfection/epidemiology/microbiology/virology ; DNA, Viral/analysis/genetics ; Disease Outbreaks ; Feces/virology ; Female ; France/epidemiology ; Genotype ; Hospitals, University/*statistics &amp; numerical data ; Humans ; Immunocompetence ; Immunocompromised Host ; Male ; *Molecular Epidemiology ; Molecular Sequence Data ; Polymerase Chain Reaction ; Seasons ; Sequence Analysis, DNA ; Viral Load ; }, abstract = {BACKGROUND: Transversal epidemiological data on adenovirus infections in a hospital setting, including both immuno-competent and transplanted patients, are limited and rarely contain the application of molecular virology.<br><br>OBJECTIVES: To describe the clinical characteristics and molecular epidemiology of adenovirus infections in Bordeaux University Hospital from 2008 to 2010 (clinical data, viral load and adenovirus species distribution).<br><br>STUDY DESIGN: Adenovirus DNA quantification (qPCR) and typing (sequencing of hexon and protein VI genes and protein VI polymerase chain reaction (PCR) product analysis) were applied retrospectively to 215 clinical samples from 105 adenovirus-infected patients (2008-2010, Bordeaux University Hospital). Clinical data were recovered and analysed for 73 children and 25 adults.<br><br>RESULTS: Viral loads were measured in stools, upper and lower respiratory fluids, blood, urine and digestive tract biopsies; the highest values were observed in stools and respiratory samples. Stool viral loads were comparable whatever the immune status. Adenovirus was typed in 57 patients: species Human adenovirus (HAdV) C dominated (n=36), followed by B (n=15), F (n=5) and D (n=1). We could demonstrate no association between HAdV species and load or clinical severity (observed in most patients). In the immuno-compromised, in contrast to immuno-competent patients, adenovirus infections presented no seasonal variation. Co-infections were frequent: mostly bacterial in immuno-competent children (33%) and viral in immuno-compromised people (34%).<br><br>CONCLUSIONS: The species HAdV C dominates the local ecology, in both respiratory and digestive tract infections, independently of the patient's immune status. Adenovirus infections, often associated with co-infection of bacterial or viral agents, frequently lead to severe clinical consequences in hospital patients.}, }
@article {pmid22607885, year = {2012}, author = {Bert, F and Larroque, B and Paugam-Burtz, C and Dondero, F and Durand, F and Marcon, E and Belghiti, J and Moreau, R and Nicolas-Chanoine, MH}, title = {Pretransplant fecal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae and infection after liver transplant, France.}, journal = {Emerging infectious diseases}, volume = {18}, number = {6}, pages = {908-916}, pmid = {22607885}, issn = {1080-6059}, mesh = {Adult ; Carrier State/*epidemiology/microbiology ; Enterobacteriaceae/enzymology/genetics ; Escherichia coli/enzymology/*genetics ; Escherichia coli Infections/*epidemiology/etiology/microbiology ; Feces/microbiology ; Female ; Humans ; Incidence ; Intraabdominal Infections/*epidemiology/etiology/microbiology ; Liver Diseases/surgery ; Liver Transplantation/*adverse effects ; Male ; Middle Aged ; Molecular Typing ; Risk Factors ; Urinary Tract Infections/*epidemiology/etiology/microbiology ; *beta-Lactam Resistance ; beta-Lactamases/genetics/metabolism ; }, abstract = {Extended-spectrum β-lactamase-producing Enterobacteriaceae isolates (ESBLE) are emerging pathogens that confer resistance to antimicrobial drugs. We conducted a 10-year study in France (January 2001-April 2010) to investigate the incidence of and risk factors for ESBLE infections after liver transplant. Of 710 transplant patients screened preoperatively for ESBLE fecal carriage, 5.5% had ESBLE infection develop within 4 months after surgery; patients with pretransplant ESBLE fecal carriage were more likely to have infection develop than were noncarriers. Typing showed extensive genetic diversity, with a large predominance of CTX-M enzymes. Independent predictors of ESBLE infection were pretransplant fecal carriage, Model for End Stage Liver Disease score >25, and return to surgery. Our results indicate that the influx of preoperatively acquired ESBLE isolates into the hospital outweighs cross-transmission in the epidemiology of ESBLE infections after liver transplant. Transplant candidates should be systematically screened for carriage, and posttransplant infection in carriers should be treated with carbapenems.}, }
@article {pmid22593832, year = {2012}, author = {Zainah, H and Silverman, A}, title = {Fecal Bacteriotherapy: A Case Report in an Immunosuppressed Patient with Ulcerative Colitis and Recurrent Clostridium difficile Infection.}, journal = {Case reports in infectious diseases}, volume = {2012}, number = {}, pages = {810943}, pmid = {22593832}, issn = {2090-6633}, abstract = {We report a case of ulcerative colitis (UC) and recurrent Clostridium difficile infection (CDI) where the patient was on immunomodulatory therapy and had successful CDI eradication after fecal transplantation. This is the first case report in the literature documenting successful C. difficile eradication in an immunosuppressed patient. We feel that fecal transplantation should be studied as a treatment option in these patients.}, }
@article {pmid22585070, year = {2012}, author = {Weissman, JS and Coyle, W}, title = {Stool transplants: ready for prime time?.}, journal = {Current gastroenterology reports}, volume = {14}, number = {4}, pages = {313-316}, pmid = {22585070}, issn = {1534-312X}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Donor Selection ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Humans ; Intestines/microbiology ; Metagenome ; Secondary Prevention ; }, abstract = {Clostridium difficile infection (CDI) is a leading cause of antibiotic- and healthcare-related diarrhea. Predisposing factors for infection include antimicrobial use, exposure to healthcare settings, inflammatory bowel disease, chemotherapy and advanced age, although CDI is now seen in patients without traditional risk factors. The gut microbiome may hold clues to the pathophysiology of CDI and promoting a 'healthy' microbiome has become a focus for CDI therapy. Stool transplant or fecal microbiota transplantation has been shown to be safe and effective for management of recurrent CDI. We offer a protocol for stool transplantation.}, }
@article {pmid22577120, year = {2012}, author = {Badger, VO and Ledeboer, NA and Graham, MB and Edmiston, CE}, title = {Clostridium difficile: epidemiology, pathogenesis, management, and prevention of a recalcitrant healthcare-associated pathogen.}, journal = {JPEN. Journal of parenteral and enteral nutrition}, volume = {36}, number = {6}, pages = {645-662}, doi = {10.1177/0148607112446703}, pmid = {22577120}, issn = {1941-2444}, mesh = {*Clostridioides difficile ; *Clostridium Infections/epidemiology/microbiology/pathology/therapy ; Humans ; *Infection Control ; }, abstract = {Clostridium difficile is the leading cause of healthcare-associated infectious diarrhea. Although C difficile is part of normal flora in some healthy individuals, patients with selective risk factors are often vulnerable to the toxigenic potential of this virulent healthcare pathogen. The spectrum of C difficile infection (CDI) is highly variable, ranging from mild to severe illness, presenting with single to multiple disease recurrences. Current approaches to treatment are based on severity of illness, number of recurrences, and clinical presentation. Oral vancomycin and metronidazole have formed the foundation for treatment of CDI, but therapeutic failures are commonly reported, especially involving hypervirulent clones. Alternative therapies, including newer antimicrobials, probiotics, immunotherapy, and fecal transplantation, have all met with varying degrees of efficacy. Although toxigenic culture (TC) testing from anaerobic culture remains the gold standard, newer technologies, including enzyme immunoassay, common antigen (glutamate dehydrogenase) testing, and real-time polymerase chain reaction (PCR) are less time-consuming and rapid. However, TC and PCR have reported high specificity and sensitivity when compared with other laboratory tests. Because of the significant morbidity and mortality associated with CDI, a high index of suspicion is warranted. Prevention and eradication of CDI require a multidisciplinary approach, including early disease recognition through appropriate surveillance, implementation of effective contact isolation strategies, adherence to environmental controls, judicious hand hygiene, evidence-based treatment, and management that includes antibiotic stewardship, continuous education of healthcare workers, and administrative support.}, }
@article {pmid22555971, year = {2012}, author = {Rodriguez-Otero, P and Porcher, R and Peffault de Latour, R and Contreras, M and Bouhnik, Y and Xhaard, A and Andreoli, A and Ribaud, P and Kapel, N and Janin, A and Socié, G and Robin, M}, title = {Fecal calprotectin and alpha-1 antitrypsin predict severity and response to corticosteroids in gastrointestinal graft-versus-host disease.}, journal = {Blood}, volume = {119}, number = {24}, pages = {5909-5917}, doi = {10.1182/blood-2011-12-397968}, pmid = {22555971}, issn = {1528-0020}, mesh = {Adolescent ; Adrenal Cortex Hormones/pharmacology/*therapeutic use ; Adult ; Aged ; Biomarkers/metabolism ; Child ; Drug Resistance ; Feces/*chemistry ; Female ; Gastrointestinal Tract/drug effects/*pathology ; Graft vs Host Disease/diagnosis/*drug therapy/*metabolism/pathology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Leukocyte L1 Antigen Complex/*metabolism ; Male ; Middle Aged ; Pancreatic Elastase/metabolism ; Regression Analysis ; Sensitivity and Specificity ; Survival Analysis ; Treatment Outcome ; Young Adult ; alpha 1-Antitrypsin/*metabolism ; }, abstract = {Diagnosis of gastrointestinal GVHD (GI-GVHD) is based on clinical symptoms and histologic findings. No biomarkers predicting responses to treatment are routinely available even though 30% to 50% of patients will not respond to corticosteroids. In this study, we aimed to evaluate fecal calprotectin, α-1-antitrypsin (α(1)-AT), and elastase at the time of first symptoms as diagnostic and prognostic tools for GI-GVHD in 72 consecutive patients, of whom 51 developed GI-GVHD. The prognostic value of markers was evaluated by their association with complete response (CR) and steroid-resistant (SR) GVHD. Calprotectin and α(1)-AT concentrations increased with GI-GVHD initial stages but patients with initial stage 1 GI-GVHD had similar marker levels to patients without GI-GVHD, so sensitivity to diagnose GI-GVHD was weak. In contrast, calprotectin and α(1)-AT were predictors for SR-GVHD and CR. Multiple regression modeling identified calprotectin and α(1)-AT concentration as independently predicting SR-GVHD together with initial stage > 2 GI-GVHD. Our results showed that fecal calprotectin and α(1)-AT levels at the time of diagnosis are predictive for responses to treatment but are not diagnostic markers for initial stage 1 to 3 GI-GVHD.}, }
@article {pmid22554078, year = {2012}, author = {Keogh, SJ and McKee, S and Smithson, SF and Grier, D and Steward, CG}, title = {Shwachman-Diamond syndrome: a complex case demonstrating the potential for misdiagnosis as asphyxiating thoracic dystrophy (Jeune syndrome).}, journal = {BMC pediatrics}, volume = {12}, number = {}, pages = {48}, pmid = {22554078}, issn = {1471-2431}, mesh = {Bone Marrow Diseases/*diagnosis ; Child ; Delayed Diagnosis ; Diagnosis, Differential ; *Diagnostic Errors ; Ellis-Van Creveld Syndrome/*diagnosis ; Exocrine Pancreatic Insufficiency/*diagnosis ; Female ; Humans ; Infant, Newborn ; Lipomatosis/*diagnosis ; Shwachman-Diamond Syndrome ; }, abstract = {BACKGROUND: The differential diagnosis of a neonate or fetus presenting with a bell-shaped or long narrow thorax includes a wide range of bony dysplasia syndromes. Where this is accompanied by respiratory distress, asphyxiating thoracic dystrophy (ATD, Jeune syndrome) is an important potential diagnosis. Shwachman-Diamond syndrome (SDS) is widely recognised as a cause of exocrine pancreatic dysfunction, short stature and bone marrow failure. It is not so well appreciated that rib and/or thoracic cage abnormalities occur in 30-50% of patients and that, in severe cases, these abnormalities may lead to thoracic dystrophy and respiratory failure in the newborn. There are, however, at least three previous case reports of children who were initially diagnosed with ATD who were subsequently shown to have SDS.<br><br>CASE PRESENTATION: This report details the case history of a patient misdiagnosed as having ATD as a neonate following the neonatal asphyxial death of her brother. She subsequently developed progressive pancytopenia but was only diagnosed with SDS at 11 years of age after referral for haematopoietic stem cell transplantation for bone marrow failure accompanied by trilineage dysplasia and clonal cytogenetic abnormalities on bone marrow examination. Subsequent testing revealed the presence of fat globules in stools, reduced faecal chymotrypsin, fat-soluble vitamin deficiency, metaphyseal dysplasia on skeletal survey and heterozygous mutations of the SBDS gene.<br><br>CONCLUSION: This report highlights the potential for diagnostic confusion between ATD and SDS. It is important to include SDS in the differential diagnosis of newborns with thoracic dystrophy and to seek expert clinical and radiological assessment of such children.}, }
@article {pmid22552243, year = {2012}, author = {McFarland, LV}, title = {The role of compassion in the practice of evidence-based medicine.}, journal = {The American journal of gastroenterology}, volume = {107}, number = {5}, pages = {768-769}, doi = {10.1038/ajg.2011.489}, pmid = {22552243}, issn = {1572-0241}, mesh = {*Clostridioides difficile ; Colon/*microbiology ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; }, abstract = {Patients with diseases having a high failure rate with standard treatments typically enroll in randomized clinical trials of new investigational treatments. Not all potential therapies are amenable to these types of designs and thus may be offered compassionately; however, claims of efficacy are thus viewed with caution. In a paper in this issue, 43 patients with recurrent Clostridium difficile infections were treated with fecal microbiota transplants using a compassionate use protocol. By using standardized healthy donor stool preparations and following standardized protocols, the 92% response rate can be viewed with more confidence than other case series reports.}, }
@article {pmid22549046, year = {2012}, author = {Kamar, N and Bendall, R and Legrand-Abravanel, F and Xia, NS and Ijaz, S and Izopet, J and Dalton, HR}, title = {Hepatitis E.}, journal = {Lancet (London, England)}, volume = {379}, number = {9835}, pages = {2477-2488}, doi = {10.1016/S0140-6736(11)61849-7}, pmid = {22549046}, issn = {1474-547X}, mesh = {Hepatitis E/*diagnosis/epidemiology/immunology/*therapy ; *Hepatitis E virus ; Humans ; }, abstract = {Hepatitis E virus (HEV) was discovered during the Soviet occupation of Afghanistan in the 1980s, after an outbreak of unexplained hepatitis at a military camp. A pooled faecal extract from affected soldiers was ingested by a member of the research team. He became sick, and the new virus (named HEV), was detected in his stool by electron microscopy. Subsequently, endemic HEV has been identified in many resource-poor countries. Globally, HEV is the most common cause of acute viral hepatitis. The virus was not initially thought to occur in developed countries, but recent reports have shown this notion to be mistaken. The aim of this Seminar is to describe recent discoveries regarding HEV, and how they have changed our understanding of its effect on human health worldwide.}, }
@article {pmid22547653, year = {2012}, author = {Jenq, RR and Ubeda, C and Taur, Y and Menezes, CC and Khanin, R and Dudakov, JA and Liu, C and West, ML and Singer, NV and Equinda, MJ and Gobourne, A and Lipuma, L and Young, LF and Smith, OM and Ghosh, A and Hanash, AM and Goldberg, JD and Aoyama, K and Blazar, BR and Pamer, EG and van den Brink, MR}, title = {Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation.}, journal = {The Journal of experimental medicine}, volume = {209}, number = {5}, pages = {903-911}, pmid = {22547653}, issn = {1540-9538}, support = {R01 HL069929/HL/NHLBI NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01-AI34495/AI/NIAID NIH HHS/United States ; R01 AI034495/AI/NIAID NIH HHS/United States ; R01-HL069929/HL/NHLBI NIH HHS/United States ; R01-AI042135/AI/NIAID NIH HHS/United States ; R01-CA107096/CA/NCI NIH HHS/United States ; R01 HL056067/HL/NHLBI NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; P01 CA142106/CA/NCI NIH HHS/United States ; P01-CA023766/CA/NCI NIH HHS/United States ; UL1 TR000064/TR/NCATS NIH HHS/United States ; P01 AI056299/AI/NIAID NIH HHS/United States ; R01 CA107096/CA/NCI NIH HHS/United States ; K23 AI095398/AI/NIAID NIH HHS/United States ; R01 AI080455/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01-HL56067/HL/NHLBI NIH HHS/United States ; R01 AI100288/AI/NIAID NIH HHS/United States ; R37 AI039031/AI/NIAID NIH HHS/United States ; R01-AI080455/AI/NIAID NIH HHS/United States ; R37-AI039031/AI/NIAID NIH HHS/United States ; }, mesh = {Ampicillin ; Animals ; Base Sequence ; *Biodiversity ; Bone Marrow Transplantation/*adverse effects ; Dextran Sulfate ; Enterocolitis/etiology/*microbiology/pathology ; Feces/microbiology ; Graft vs Host Disease/*complications/microbiology ; Gram-Positive Bacteria/isolation &amp; purification ; Humans ; Metagenome/*genetics ; Mice ; Molecular Sequence Data ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Species Specificity ; Transplantation, Homologous ; }, abstract = {Despite a growing understanding of the link between intestinal inflammation and resident gut microbes, longitudinal studies of human flora before initial onset of intestinal inflammation have not been reported. Here, we demonstrate in murine and human recipients of allogeneic bone marrow transplantation (BMT) that intestinal inflammation secondary to graft-versus-host disease (GVHD) is associated with major shifts in the composition of the intestinal microbiota. The microbiota, in turn, can modulate the severity of intestinal inflammation. In mouse models of GVHD, we observed loss of overall diversity and expansion of Lactobacillales and loss of Clostridiales. Eliminating Lactobacillales from the flora of mice before BMT aggravated GVHD, whereas reintroducing the predominant species of Lactobacillus mediated significant protection against GVHD. We then characterized gut flora of patients during onset of intestinal inflammation caused by GVHD and found patterns mirroring those in mice. We also identified increased microbial chaos early after allogeneic BMT as a potential risk factor for subsequent GVHD. Together, these data demonstrate regulation of flora by intestinal inflammation and suggest that flora manipulation may reduce intestinal inflammation and improve outcomes for allogeneic BMT recipients.}, }
@article {pmid22538059, year = {2012}, author = {Pérez-Gracia, MT and Mateos-Lindemann, ML}, title = {[Hepatitis E. Current perspectives].}, journal = {Medicina clinica}, volume = {139}, number = {9}, pages = {404-411}, doi = {10.1016/j.medcli.2012.02.013}, pmid = {22538059}, issn = {1578-8989}, mesh = {Acute Disease ; Chronic Disease ; Global Health ; *Hepatitis E/diagnosis/epidemiology/therapy/virology ; Hepatitis E virus/classification/genetics ; Humans ; }, abstract = {Infection with hepatitis E virus (HEV) is highly prevalent in developing countries and the WHO estimates one third of the world population has had contact with the virus. Its diagnosis and epidemiology are well known in endemic countries but, recently, there have been sporadic cases in developed countries in patients with no history of travel. Currently in these countries, hepatitis E is considered a zoonosis yet there remain to be known other routes of transmission. Another interesting aspect is that HEV can cause chronic hepatitis in transplanted patients, other immunocompromised patients and even in immunocompetent people. There have also been reported cases of fulminant hepatitis and other extrahepatic manifestations. The diagnosis is based on serological studies and detection of viral RNA in blood and feces. The vaccine is a good option to prevent this infection that affects a large number of people in deprived geographical areas but unfortunately it is not available yet.}, }
@article {pmid22508484, year = {2013}, author = {Berg, AM and Kelly, CP and Farraye, FA}, title = {Clostridium difficile infection in the inflammatory bowel disease patient.}, journal = {Inflammatory bowel diseases}, volume = {19}, number = {1}, pages = {194-204}, doi = {10.1002/ibd.22964}, pmid = {22508484}, issn = {1536-4844}, mesh = {Clostridioides difficile/*pathogenicity ; Clostridium Infections/*complications ; Humans ; Inflammatory Bowel Diseases/*etiology/therapy ; }, abstract = {Clostridium difficile infection (CDI) has been increasing in frequency and severity in patients with inflammatory bowel disease (IBD). Population based and single center studies have shown worse clinical outcomes in concomitant CDI and IBD, with several reporting longer length of hospital stay, higher colectomy rates and increased mortality. Clinically, CDI may be difficult to distinguish from an IBD flare and may range from an asymptomatic carrier state to severe life threatening colitis. The traditional risk factors for CDI have included hospitalization, antibiotic use, older age and severe co-morbid disease but IBD patients have several distinct characteristics including younger age, community acquisition, lack of antibiotic exposure, colonic IBD and steroid use. CDI can occur in the small bowel and specifically in ulcerative colitis patients who have had a colectomy and an ileal pouch anal anastomosis. PCR based assays and combination Elisa algorithms have improved the sensitivity and specificity of testing, though in IBD patients have raised clinical questions about how to best manage diarrhea in the setting of possible C. difficile colonization. Treatment modalities for CDI have not been examined in randomized clinical trials in the IBD population. Newer antibiotics, immunotherapy and fecal microbiota transplantation may alter current treatment strategies. This review will focus on the unique epidemiology of CDI in IBD patients, detail clinical disease states, and provide updated diagnostic strategies, prevention and treatment options.}, }
@article {pmid22499011, year = {2012}, author = {Henke-Gendo, C and Ganzenmueller, T and Kluba, J and Harste, G and Raggub, L and Heim, A}, title = {Improved quantitative PCR protocols for adenovirus and CMV with an internal inhibition control system and automated nucleic acid isolation.}, journal = {Journal of medical virology}, volume = {84}, number = {6}, pages = {890-896}, doi = {10.1002/jmv.23285}, pmid = {22499011}, issn = {1096-9071}, mesh = {Adenoviruses, Human/genetics/*isolation &amp; purification ; Automation/*methods ; Blood/virology ; Bronchoalveolar Lavage Fluid/virology ; Cytomegalovirus/genetics/*isolation &amp; purification ; DNA, Viral/isolation &amp; purification ; Feces/virology ; Humans ; Real-Time Polymerase Chain Reaction/*methods/*standards ; Reference Standards ; Sensitivity and Specificity ; Specimen Handling/methods ; Viral Load/*methods/*standards ; }, abstract = {With the establishment of routine virus load (DNAemia) screening for Human adenovirus (HAdV) and Cytomegalovirus (CMV) in post-transplant care quality standards for quantitative PCR-assays are increasing. Established real-time PCR assays were improved with a fully automated DNA-extraction and with a competitive internal control DNA packaged into a lambda phage which serves as an extraction and amplification control in each sample. HAdV and CMV DNA were detected and quantified simultaneously in various types of diagnostic samples like blood, feces or respiratory tract materials. Inhibition was observed in 0.33-0.66% of over 14,000 diagnostic samples, an infrequent but nevertheless not negligible event, which is observed mainly in stool samples. CMV viral load in broncho-alveolar lavage fluid (BALF) ranged between positive but below the quantitation limit of 1,000 copies/ml up to 1.8 × 10(7) copies/ml with a median of 6.0 × 10(3) copies/ml. Forty-one (4.7%) BALF samples had a viral load above 5.0 × 10(5) copies/ml, which was proposed as a threshold for the diagnosis of pneumonia. HAdV viral loads ranged between positive but below the quantitation limit of 1,000 copies/ml to a very high concentration of 1.3 × 10(11) copies/ml in stool and BALF samples. A HAdV-DNAemia of >10(4) copies/ml was found only in patients with stool viral load of above 10(5) copies/ml. These data support the hypothesis that quantitation in diagnostic materials other than blood may give valuable diagnostic information and that further evaluation of this approach is reasonable.}, }
@article {pmid22493792, year = {2012}, author = {Parnaby, CN and Barrow, EJ and Edirimanne, SB and Parrott, NR and Frizelle, FA and Watson, AJ}, title = {Colorectal complications of end-stage renal failure and renal transplantation: a review.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {14}, number = {4}, pages = {403-415}, doi = {10.1111/j.1463-1318.2010.02491.x}, pmid = {22493792}, issn = {1463-1318}, mesh = {Colonic Diseases/diagnosis/epidemiology/*etiology/therapy ; Humans ; Kidney Failure, Chronic/*complications/surgery ; *Kidney Transplantation ; *Postoperative Complications/diagnosis/epidemiology/therapy ; Prevalence ; Rectal Diseases/diagnosis/epidemiology/*etiology/therapy ; Treatment Outcome ; }, abstract = {AIM: End-stage renal failure (ESRF) and renal transplant recipients are thought to be associated with an increased risk of colorectal complications.<br><br>METHOD: A review of the literature was performed to assess the prevalence and outcome in both benign and malignant colorectal disease.<br><br>RESULTS: No prospective randomized studies assessing colorectal complications in ESRF or renal transplant were identified. Case series and case reports have described the incidence and management of benign colorectal complications. Complications included diverticulitis,infective colitis, colonic bleeding and colonic perforation. There was insufficient evidence to associated iverticular disease with adult polycystic kidney disease.Three population-based studies have shown up to a twofold increased incidence of colonic cancer but not rectal cancer for renal transplant recipients. Bowel cancer screening (as per the general population) by faecal occult blood testing appears justified for renal transplant patients; however, evidence suggests that consideration of starting screening at a younger age may be worthwhile because of an increased risk of developing colonic cancer.Two population-based studies have shown a threefold and 10-fold increased incidence of anal cancer for renal transplant recipients. A single case&#x2013;control study demonstrated significant increased prevalence of anal human papilloma virus (HPV) and intraepithelial neoplasia (AIN)in patients with established renal transplants.<br><br>CONCLUSIONS: Despite the lack of high-level evidence,ESRF and renal transplantation were associated with colorectal complications that could result in major morbidity and mortality. Bowel cancer screening in this patient group appears justified. The effectiveness of screening for HPV, AIN and anal cancer in renal transplant recipients remains unclear.}, }
@article {pmid22489846, year = {2012}, author = {Hourigan, SK and Anders, RA and Mitchell, SE and Schwarz, KB and Lau, H and Karnsakul, W}, title = {Chronic diarrhea, ascites, and protein-losing enteropathy in an infant with hepatic venous outflow obstruction after liver transplantation.}, journal = {Pediatric transplantation}, volume = {16}, number = {7}, pages = {E328-31}, pmid = {22489846}, issn = {1399-3046}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; }, mesh = {Anastomosis, Surgical ; Ascites/*complications/etiology ; Budd-Chiari Syndrome/complications/*etiology ; Constriction, Pathologic ; Diarrhea/*complications/etiology ; Female ; Humans ; Infant ; Liver/diagnostic imaging/pathology ; Liver Failure/*complications/therapy ; Liver Transplantation/*adverse effects ; Postoperative Complications ; Protein-Losing Enteropathies/*complications/etiology ; Recurrence ; Serum Albumin/metabolism ; Ultrasonography/methods ; Vascular Surgical Procedures/methods ; }, abstract = {An 18-month-old female status post-orthotopic liver transplant for biliary atresia presented nine months after transplant with severe diarrhea and intolerance of feeds. She was found to have a PLE as evidenced by a low serum albumin and a persistent elevation of fecal A1AT. Investigation eventually revealed that the cause of the PLE was a stricture at the anastomosis site between the hepatic vein and inferior cava, supported by resolution of the PLE after venoplasty of the stricture. The patient has subsequently required several repeat venoplasties for recurrence of her symptoms correlating with recurrence of the stricture. This is a very rare presentation of hepatic venous outflow obstruction. Moreover, normal duplex ultrasound imaging of liver vasculature and her unusual presentation led to a delay in her diagnosis highlighting the need for an increased index of suspicion.}, }
@article {pmid22468996, year = {2012}, author = {Jorup-Rönström, C and Håkanson, A and Sandell, S and Edvinsson, O and Midtvedt, T and Persson, AK and Norin, E}, title = {Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients.}, journal = {Scandinavian journal of gastroenterology}, volume = {47}, number = {5}, pages = {548-552}, doi = {10.3109/00365521.2012.672587}, pmid = {22468996}, issn = {1502-7708}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/adverse effects/therapeutic use ; Bacteria, Anaerobic ; Biological Therapy ; *Clostridioides difficile ; Clostridium Infections/complications/drug therapy ; Colon/microbiology ; Colonoscopy ; Diarrhea/*microbiology/*therapy ; Enema ; Feces/*microbiology ; Female ; Humans ; Male ; Metagenome/drug effects ; Middle Aged ; Rectum/microbiology ; Recurrence ; }, abstract = {Clostridium difficile-associated disease (CDAD) with frequent watery stools, sometimes with painful bowel movements, fever and sickness, is probably the major known cause of antibiotic-associated diarrhea and colitis, most probably depending on a disruption of the normal intestinal balance in the microbiome. In this study, we have inoculated a mixture of fecal microbes--as an enema--originating from a healthy Scandinavian middle-aged donor, regularly re-cultivated under strict anaerobic conditions for more than 10 years, to 32 patients. Twenty-two patients (69%) were durably cured. In those patients receiving the transplant by colonoscopy, four out of five were cured. To the best of our knowledge, this is the first time a fecal culture of microbes has retained the possibility for years to cure a substantial number of patients with CDAD.}, }
@article {pmid22464833, year = {2011}, author = {Yang, CT and Chen, HL and Ho, MC and Shinn-Forng Peng, S}, title = {Computed tomography indices and criteria for the prediction of esophageal variceal bleeding in survivors of biliary atresia awaiting liver transplantation.}, journal = {Asian journal of surgery}, volume = {34}, number = {4}, pages = {168-174}, doi = {10.1016/j.asjsur.2011.11.006}, pmid = {22464833}, issn = {0219-3108}, mesh = {Adolescent ; Biliary Atresia/*complications/surgery ; Child ; Child, Preschool ; Decision Support Techniques ; Endoscopy, Digestive System ; Esophageal and Gastric Varices/diagnosis/*diagnostic imaging/etiology ; Female ; Gastrointestinal Hemorrhage/diagnosis/*diagnostic imaging/etiology ; Humans ; Infant ; Liver/*diagnostic imaging ; Liver Transplantation ; Male ; *Multidetector Computed Tomography ; Occult Blood ; ROC Curve ; Retrospective Studies ; Risk Assessment ; Spleen/*diagnostic imaging ; }, abstract = {BACKGROUND/OBJECTIVE: About 20% of biliary atresia (BA) survivors have attacks of esophageal variceal bleeding. We propose a method to evaluate the risk of esophageal variceal bleeding (EVB) using noninvasive indices by multislice computed tomography (CT).<br><br>METHODS: We reviewed 31 potential living-related liver recipients aged 99-5314 days (mean, 1474 days) who underwent CT examinations using a 64-slice multislice CT scanner. Of the 31 patients, 19 patients (Group A) with fecal occult blood had EVB on esophagogastroduodenoscopy; the rest belonged to Group B. Splenic diameters (mm) were divided by body heights (m) and platelet counts (1000/mm(3)) to produce standardized ratios of transverse splenic length/body height/platelet count (SLHPR). The transverse diameters of paraesophageal veins (PVs) and perigastric veins (PGVs) were measured adjacent to the lower thoracic esophagus and within the lesser sac, respectively.<br><br>RESULTS: According to a receiver operating characteristic curve analysis, the SLHPRs (r=0.833), transverse PV (r=0.957), and PGV (r=0.987) diameters were better predictors of EVB than demographic and laboratory variables. However, the transverse diameters of PGVs and PVs were the most accurate predictors of the EVB.<br><br>CONCLUSION: For candidates awaiting liver transplantation, screening by noninvasive SLHPR and the transverse diameters of PGVs and PVs by CT may help to identify BA patients with a high risk of EVB.}, }
@article {pmid22450732, year = {2012}, author = {Brandt, LJ and Aroniadis, OC and Mellow, M and Kanatzar, A and Kelly, C and Park, T and Stollman, N and Rohlke, F and Surawicz, C}, title = {Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection.}, journal = {The American journal of gastroenterology}, volume = {107}, number = {7}, pages = {1079-1087}, doi = {10.1038/ajg.2012.60}, pmid = {22450732}, issn = {1572-0241}, mesh = {Aged ; Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Colonoscopy ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Male ; Metagenome ; Recurrence ; Surveys and Questionnaires ; United States ; Vancomycin/therapeutic use ; }, abstract = {OBJECTIVES: Clostridium difficile infection (CDI) has increased to epidemic proportions over the past 15 years, and recurrence rates of 30-65% with failure to respond to multiple courses of antimicrobials are common. The aim of this study was to report the efficacy of fecal microbiota transplantation (FMT) in patients with recurrent CDI in five geographically disparate medical centers across the United States.<br><br>METHODS: A multicenter long-term follow-up study was performed on the use of FMT for recurrent CDI. We were able to contact 77 of 94 eligible patients who had colonoscopic FMT for recurrent CDI &#x2265; 3 months before. Respondents completed a 36-item questionnaire via mail and/or phone that solicited pre-FMT, post-FMT, and donor data. Study outcomes included primary cure rate (resolution of symptoms without recurrence within 90 days of FMT) and secondary cure rate (resolution of symptoms after one further course of vancomycin with or without repeat FMT).<br><br>RESULTS: Seventy-three percent of patients were women and the average age was 65 years. The long-term follow-up period ranged from 3 to 68 months between FMT and data collection (mean: 17 months). The majority of patients were living independently at the time of FMT; however, 40% were ill enough to be hospitalized, homebound, or living in a skilled nursing facility. Spouses and partners accounted for 60% of donors and 27% were either first-degree relatives or otherwise related to the patient. The average symptom duration before FMT was 11 months and patients had failed an average of five conventional antimicrobial regimens; nonetheless, 74% of patients had resolution of their diarrhea in &#x2264; 3 days. Diarrhea resolved in 82% and improved in 17% of patients within an average of 5 days after FMT. The primary cure rate was 91%. Seven patients either failed to respond or experienced early CDI recurrence (&#x2264; 90 days) after FMT. Four of these patients were successfully treated with vancomycin with or without probiotics; two patients were treated unsuccessfully with vancomycin, but subsequent FMT was successful; one patient was not treated and died in hospice care of unclear cause. The secondary cure rate was 98%. All late recurrences of CDI occurred in the setting of antimicrobial therapy for treatment of infections unrelated to C. difficile. In all, 53% of patients stated they would have FMT as their preferred first treatment option if CDI were to recur. While no definite adverse effects of FMT were noted, two patients had improvement in a pre-existing medical condition and four patients developed diseases of potential interest after FMT.<br><br>CONCLUSIONS: FMT is a rational, durable, safe, and acceptable treatment option for patients with recurrent CDI.}, }
@article {pmid22450020, year = {2012}, author = {Gallegos-Orozco, JF and Paskvan-Gawryletz, CD and Gurudu, SR and Orenstein, R}, title = {Successful colonoscopic fecal transplant for severe acute Clostridium difficile pseudomembranous colitis.}, journal = {Revista de gastroenterologia de Mexico}, volume = {77}, number = {1}, pages = {40-42}, pmid = {22450020}, issn = {0375-0906}, mesh = {Acute Disease ; Aged ; *Colonoscopy ; Enterocolitis, Pseudomembranous/*therapy ; *Feces ; Humans ; Male ; Remission Induction ; Severity of Illness Index ; }, abstract = {Clostridium difficile-associated diarrhea has become one of the most common healthcare-associated infections, with significant morbidity and mortality, especially among the elderly in the inpatient setting. The standard approach with metronidazole and vancomycin is not very effective in treating patients with severe colitis and hence other alternatives have been explored. We herein describe the first successful experience of colonoscopic fecal transplant in a case of severe refractory C. difficile pseudomembranous colitis.}, }
@article {pmid22430504, year = {2012}, author = {Xie, Y and Luo, Z and Li, Z and Deng, M and Liu, H and Zhu, B and Ruan, B and Li, L}, title = {Structural shifts of fecal microbial communities in rats with acute rejection after liver transplantation.}, journal = {Microbial ecology}, volume = {64}, number = {2}, pages = {546-554}, pmid = {22430504}, issn = {1432-184X}, mesh = {Animals ; Bacteria/*classification/*genetics/growth &amp; development ; Bacteroides/genetics/growth &amp; development ; Bifidobacterium/genetics ; Denaturing Gradient Gel Electrophoresis/methods ; Feces/*microbiology ; *Graft Rejection ; Intestinal Mucosa/microbiology ; Liver/metabolism/pathology ; *Liver Transplantation ; Male ; Metagenome ; Polymerase Chain Reaction/methods ; Rats ; Rats, Inbred Lew ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Ruminococcus/genetics/growth &amp; development ; }, abstract = {Bacterial translocation and the development of sepsis after orthotopic liver transplantation (OLT) may be promoted by immunological damage to the intestinal mucosa or by quantitative and qualitative changes in intestinal microbiota. This study monitored structural shifts of gut microbiota in rats with OLT using PCR-denaturing gradient gel electrophoresis (DGGE) and real-time quantitative PCR (RT-qPCR). RT-qPCR targets six major microorganisms (Domain Bacteria, Bacteroides, Bifidobacteria, Enterobacteriaceae, Lactobacillus and Clostridium leptum subgroup). Isograft, Allograft and Sham model were studied. Bacterial translocation to host organs and plasma endotoxin were determined. Alteration in gut microbiota was associated with the elevation of plasma endotoxin and a higher rate of bacterial translocation (BT) to liver in rats with acute rejection. Dynamic analysis of DGGE fingerprints showed that the gut microbiota structure of animals in the three groups was similar before the operation. But significant alterations in the composition of fecal microbiota in Allograft group were observed at 1 and 2 weeks after the OLT. The acute rejection was accompanied by the shifts of gut microbiota towards members of Bacteroides and Ruminococcus. Results from RT-qPCR indicated that Bacteroides significantly increased at 2 weeks after the OLT, whereas numbers of Bifidobacterium spp. decreased at 1 week and recovered at 2 weeks after the OLT. In summary, our data showed that rats with acute rejection after OLT exhibited significant structure shifts in the gut microbiota which dominant by overgrowth of Bacteroides and Ruminococcus, and these were associated with elevation of plasma endotoxin and higher rate of BT.}, }
@article {pmid22388862, year = {2012}, author = {Hemann, M and Shen, HG and Beach, NM and Meng, XJ and Halbur, PG and Opriessnig, T}, title = {Expression of human CD46 has no effect on porcine circovirus type 2 infection and shedding in the experimental pig model.}, journal = {Veterinary research communications}, volume = {36}, number = {3}, pages = {187-193}, pmid = {22388862}, issn = {1573-7446}, mesh = {Animals ; Animals, Genetically Modified/genetics/*immunology ; Antibodies, Viral/blood/genetics ; Circoviridae Infections/immunology/veterinary/virology ; Circovirus/*classification/genetics ; DNA, Viral/blood/genetics ; Enzyme-Linked Immunosorbent Assay/veterinary ; Humans ; Membrane Cofactor Protein/blood/*metabolism ; Random Allocation ; Real-Time Polymerase Chain Reaction/veterinary ; Swine/genetics/*immunology ; Swine Diseases/immunology/virology ; Transgenes ; Transplantation, Heterologous ; Viremia/veterinary ; Virus Shedding ; }, abstract = {Xenotransplantation of tissues from transgenic pigs with desired genetic modifications such as CD46 expression help minimize xenograft rejections. However, CD46 is a known receptor for some viruses. In this study, pigs transgenic for human CD46 (CD46-TG) and appropriate non-transgenic (non-TG) control pigs were utilized to determine possible differences in the level of replication and shedding of porcine circovirus type 2 (PCV2). Non-TG and CD46-TG were blocked by transgenic status and randomly divided into three groups: Non-TG negative controls (n = 3), non-TG-PCV2 (n = 10; PCV2a = 5, PCV2b = 5), and CD46-TG-PCV2 (n = 6; PCV2a = 3, PCV2b = 3). Blood, oral, nasal and fecal swabs were collected at regular intervals from the day of arrival until 70 days post inoculation (DPI). All samples were tested by quantitative real-time PCR for the presence of PCV2 DNA and serum was tested for presence of PCV2 antibodies by ELISA. Overall, the main effects "transgenic status" and "PCV2 subtype" had no influence on degree of PCV2 viremia and shedding or the anti-PCV2 humoral immune response in CD46-TG-PCV2 pigs compared to non-TG-PCV2 pigs. Differences in PCV2 concentrations between non-TG-PCV2 and CD46-TG-PCV2 pigs were minimal and limited to DPI 35 in sera, DPI 7 in fecal swabs and DPI 5 in nasal swabs when CD46-TG-PCV2 pigs had significantly higher concentrations of PCV2 DNA. At DPI 1, CD46-TG-PCV2 pigs had significantly lower concentrations of PCV2 DNA in oral swabs. Under the study conditions, the presence of human CD46 in transgenic pigs had no effect on PCV2 infection in otherwise healthy pigs capable of a normal immune response.}, }
@article {pmid22386306, year = {2012}, author = {Rodríguez-Frias, F and Jardi, R and Buti, M}, title = {[Hepatitis E: molecular virology, epidemiology and pathogenesis].}, journal = {Enfermedades infecciosas y microbiologia clinica}, volume = {30}, number = {10}, pages = {624-634}, doi = {10.1016/j.eimc.2012.01.014}, pmid = {22386306}, issn = {1578-1852}, mesh = {Animals ; Antiviral Agents/therapeutic use ; Base Sequence ; Female ; Food Contamination ; Genes, Viral ; Genotype ; *Hepatitis E/diagnosis/drug therapy/epidemiology/transmission/veterinary/virology ; Hepatitis E virus/classification/genetics/physiology ; Humans ; Liver Cirrhosis/epidemiology/etiology ; Male ; Mammals/virology ; Molecular Sequence Data ; Organ Transplantation/adverse effects ; Postoperative Complications/virology ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology/virology ; RNA, Viral/genetics ; Serotyping ; Swine ; Swine Diseases/epidemiology/virology ; Transfusion Reaction ; Viral Hepatitis Vaccines ; Virus Replication ; Zoonoses ; }, abstract = {Hepatitis E represents a significant proportion of enteric transmitted liver diseases and poses a major public health problem, mainly associated with epidemics due to contamination of water supplies, especially in developing countries. Hepatitis E virus (HEV) is responsible for self-limiting acute liver oral-faecal infections. In industrialised countries, acute hepatitis E is sporadic, detected in travellers from endemic areas but also in sporadic cases with no risk factors. HEV is a non-enveloped virus with a single-stranded RNA genome classified into 4 genotypes and a single serotype. Genotypes 1 and 2 only infect humans, and are predominant in the developing countries, while 3 and 4 are predominant in industrialised countries, and also infect other species of mammals, especially pigs, and multiple evidence classifies HEV as a zoonotic agent. Some HEV chronic infections have recently been reported in kidney and liver transplant patients. The mortality rate of HEV infection is greater than hepatitis A. In addition to faecal-oral transmission, parenteral transmission of HEV has also been reported. Several vaccines are currently in development. The severity of this infection in some groups of patients, especially pregnant women, and the occurrence of chronic hepatitis, even with progression to cirrhosis, have raised interest in the application of interferon and/or ribavirin therapy.}, }
@article {pmid22360412, year = {2012}, author = {Guo, B and Harstall, C and Louie, T and Veldhuyzen van Zanten, S and Dieleman, LA}, title = {Systematic review: faecal transplantation for the treatment of Clostridium difficile-associated disease.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {35}, number = {8}, pages = {865-875}, doi = {10.1111/j.1365-2036.2012.05033.x}, pmid = {22360412}, issn = {1365-2036}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Metagenome/*physiology ; Microbial Interactions ; }, abstract = {BACKGROUND: Management of recurrent Clostridium difficile-associated disease (CDAD), particularly in elderly patients, remains clinically challenging. Faecal transplantation (FT) may restore normal microbiota and break the cycle of recurrent CDAD.<br><br>AIM: To critically appraise the clinical research evidence on the safety and effectiveness of FT compared with standard care in the treatment of patients with CDAD.<br><br>METHODS: A comprehensive literature search was conducted by a research librarian to identify relevant studies published between 2000 and 2011. The Cochrane Library, PubMed, EMBASE, CINAHL, Biological Abstracts, BIOSIS Previews and Web of Science were searched using the following Medical Subject Headings (MeSH) terms and keywords, alone or in combination: Clostridium infections/Clostridium difficile/pseudomembranous/colitis/faeces/rectal/colon flora/gastrointestinal/nasogastric tube/enema/donor/transplant/infusion/bacteriotherapy/human probiotic infusion. Methodological quality of the included case series studies was assessed in terms of patient selection criteria, consecutive recruitment, prospective data collection, reporting of lost to follow-up, and follow-up rates.<br><br>RESULTS: No controlled studies were found. Based on the weak evidence from seven full-text case series studies of 124 patients with recurrent/refractory CDAD, FT appears to be a safe and effective procedure. In most cases (83%) symptoms improved immediately after the first FT procedure, and some patients stayed diarrhoea free for several months or years.<br><br>CONCLUSIONS: Although these results appear to be promising, the treatment effects of faecal transplantation cannot be determined definitively in the absence of a control group. Results from randomised controlled trials that compare faecal transplantation to oral vancomycin without or with a taper regimen will help to better define the role of faecal transplantation in the management of recurrent CDAD.}, }
@article {pmid22317949, year = {2012}, author = {Goldsmith, HS}, title = {Author's reply: To PMID 21943947.}, journal = {American journal of surgery}, volume = {204}, number = {5}, pages = {805-806}, doi = {10.1016/j.amjsurg.2011.11.004}, pmid = {22317949}, issn = {1879-1883}, mesh = {Anal Canal/*injuries ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Pylorus/*blood supply/*transplantation ; Wounds and Injuries/*surgery ; }, }
@article {pmid22307017, year = {2012}, author = {Bastos Oreiro, M and Castilla-Llorente, C and de la Guía, AL and de Paz, R and Van Domselaar, M and Nieto, J and Rodriguez, A and Gallardo, D and Canales, M and , }, title = {Fecal calprotectin in allogeneic stem cell transplantation for the diagnosis of acute intestinal graft versus host disease.}, journal = {Bone marrow transplantation}, volume = {47}, number = {9}, pages = {1241-1242}, doi = {10.1038/bmt.2011.241}, pmid = {22307017}, issn = {1476-5365}, mesh = {Adult ; Feces/*chemistry ; Graft vs Host Disease/*diagnosis/etiology/metabolism ; Hematopoietic Stem Cell Transplantation/adverse effects/*methods ; Humans ; Leukocyte L1 Antigen Complex/*analysis/metabolism ; Middle Aged ; Prospective Studies ; Transplantation, Homologous ; }, }
@article {pmid22306636, year = {2012}, author = {Woodward, S}, title = {Management of faecal incontinence in graft-versus-host disease.}, journal = {British journal of nursing (Mark Allen Publishing)}, volume = {21}, number = {2}, pages = {84, 86-8}, doi = {10.12968/bjon.2012.21.2.84}, pmid = {22306636}, issn = {0966-0461}, mesh = {Adult ; Dermatitis/etiology/nursing ; Diarrhea/etiology/nursing ; Fatal Outcome ; Fecal Incontinence/*etiology/*nursing ; Female ; Graft vs Host Disease/*complications/*nursing ; Hematopoietic Stem Cell Transplantation/*adverse effects/*nursing ; Humans ; Male ; Middle Aged ; Terminal Care/methods ; }, abstract = {Graft-versus-host disease (GvHD), a common yet serious complication of allogeneic haemopoietic stem cell transplantation, can cause significant morbidity and negatively impact on patients' quality of life. The gastrointestinal tract is frequently affected resulting in nausea and vomiting, abdominal pain and profuse diarrhoea (Washington and Jagasia, 2009) which can be both distressing and humiliating for patients. The volume of watery, green diarrhoea produced can be greater than 2 litres per day (Ferrara et al, 2009) and is one indicator of the severity of GvHD. It may, in some cases, lead to faecal incontinence. Management of GvHD-associated diarrhoea involves the use of high-dose steroids to control the exaggerated immune response, anti-diarrhoeal medication, management of fluid and electrolytes, and nutritional management. It may also require management of faecal incontinence and prevention of incontinence-associated dermatitis. This paper describes the pathology of GvHD, the management of GvHD-associated diarrhoea and faecal incontinence and discusses the potential use of a faecal management system inappropriately selected individuals with uncontrolled diarrhoea and limited mobility.}, }
@article {pmid22306431, year = {2012}, author = {Chandra, A}, title = {Reply to: Should we, not could we? A commentary on "Pyloric valve transposition as substitute for a colostomy in humans: a preliminary report".}, journal = {American journal of surgery}, volume = {204}, number = {5}, pages = {806-807}, doi = {10.1016/j.amjsurg.2011.11.003}, pmid = {22306431}, issn = {1879-1883}, mesh = {Anal Canal/*injuries ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Pylorus/*blood supply/*transplantation ; Wounds and Injuries/*surgery ; }, }
@article {pmid22305239, year = {2012}, author = {Li, Q and Wang, C and Zhang, Q and Tang, C and Li, N and Ruan, B and Li, J}, title = {Use of 18S ribosomal DNA polymerase chain reaction-denaturing gradient gel electrophoresis to study composition of fungal community in 2 patients with intestinal transplants.}, journal = {Human pathology}, volume = {43}, number = {8}, pages = {1273-1281}, doi = {10.1016/j.humpath.2011.09.017}, pmid = {22305239}, issn = {1532-8392}, mesh = {Adolescent ; Adult ; DNA, Fungal/*genetics ; Denaturing Gradient Gel Electrophoresis ; Feces/*microbiology ; Fungi/classification/*genetics ; Humans ; Intestines/*microbiology/*transplantation ; Male ; RNA, Ribosomal, 18S/*genetics ; }, abstract = {Fungi form a diverse microbial community in the human intestine. Little is known about the succession of species after intestinal transplantation. We investigated the alterations of the gut fungal population in 2 patients with intestinal allografts. The ileal effluent and feces were fingerprinted using denaturing gradient gel electrophoresis, with confirmation by DNA sequencing. Analysis of 18S ribosomal DNA indicated that the phylogenetic diversity of the fungal communities was higher soon after transplantation; less diversity was observed at the later time points in patient 1. The shifts in the denaturing gradient gel electrophoresis banding patterns over time were similar in the effluent and feces in this patient. Similar changes in the fungi in the effluent and feces also were observed in patient 2. Sequence analysis of denaturing gradient gel electrophoresis bands showed that Saccharomyces cerevisiae and Kluyveromyces waltii dominated the fungal microbiota in both patients. Some species, including Candida spp, Cryptococcus neoformans, Fusarium oxysporum, Aspergillus clavatus, and Trichophyton verrucosum, were present early. We report for the first time the temporal alterations in fungal communities in patients with an intestinal allograft. This information may provide novel insight into the roles of the fungal microbiota in the pathophysiology of the transplanted intestine.}, }
@article {pmid22300955, year = {2012}, author = {Naseer, U and Eriksen, BO and Sundsfjord, A and Samuelsen, &#xd8;}, title = {Fecal colonization of VIM-1-producing Klebsiella pneumoniae and in vivo transfer of multidrug-resistant IncN plasmid in a renal transplant patient.}, journal = {Diagnostic microbiology and infectious disease}, volume = {72}, number = {4}, pages = {363-366}, doi = {10.1016/j.diagmicrobio.2011.12.010}, pmid = {22300955}, issn = {1879-0070}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; DNA, Bacterial/genetics ; Drug Resistance, Multiple, Bacterial/*genetics ; Escherichia coli/drug effects/genetics ; Feces/*microbiology ; *Gene Transfer, Horizontal ; Humans ; Kidney Transplantation/*adverse effects ; Klebsiella Infections/microbiology ; Klebsiella pneumoniae/drug effects/enzymology/*growth &amp; development/isolation &amp; purification ; Plasmids/*genetics ; Polymerase Chain Reaction ; beta-Lactamases/biosynthesis/genetics ; }, abstract = {We report a case of long-term colonization of a carbapenemase (VIM)-producing Klebsiella pneumoniae clone in a renal transplant patient and demonstrate the in vivo transmission of a broad-host-range multidrug-resistant IncN plasmid containing bla(VIM), bla(SHV-12), and qnrS to Escherichia coli.}, }
@article {pmid22294413, year = {2012}, author = {Dons, EM and Echeverri, GJ and Rigatti, LH and Klein, E and Montoya, C and Wolf, RF and Ijzermans, JN and Cooper, DK and Wagner, R}, title = {Collagenous colitis-like condition in immunosuppressed infant baboons.}, journal = {Inflammatory bowel diseases}, volume = {18}, number = {7}, pages = {1325-1332}, pmid = {22294413}, issn = {1536-4844}, support = {R21 AI074844/AI/NIAID NIH HHS/United States ; U01 AI068642-04/AI/NIAID NIH HHS/United States ; U01 AI068642/AI/NIAID NIH HHS/United States ; P40 RR012317-09/RR/NCRR NIH HHS/United States ; P40 RR012317/RR/NCRR NIH HHS/United States ; R21 AI074844-02/AI/NIAID NIH HHS/United States ; R21 A1074844//PHS HHS/United States ; R24 RR016556/RR/NCRR NIH HHS/United States ; U19 AI090959-03/AI/NIAID NIH HHS/United States ; U19 AI090959/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn ; Anti-Inflammatory Agents/therapeutic use ; Budesonide/therapeutic use ; Colitis, Collagenous/*etiology/immunology/*pathology ; Diarrhea/drug therapy/etiology/*pathology ; Female ; Humans ; Immunosuppression Therapy ; Immunosuppressive Agents/*adverse effects ; Male ; Papio ; Weight Loss ; }, abstract = {BACKGROUND: Collagenous colitis is a chronic inflammatory bowel disease of unknown etiology. It is fairly common in adult humans, but rare in infants, and has been associated with autoimmune disorders.<br><br>METHODS: We report four infant baboons (age 7-12 months) that had received a transplant at 3 months of age and subsequent immunosuppressive therapy for periods of 4-10 months. All presented identical symptoms within a period of 4 weeks, including weight loss associated with chronic watery diarrhea that was unresponsive to standard antimicrobial treatment.<br><br>RESULTS: Clinical chemistry evaluations were within normal ranges, viral causes were ruled out, and fecal and blood cultures were repeatedly negative. At necropsy, two infant baboons were found to have a form of collagenous colitis. In the remaining two baboons that had identical clinical features, immunosuppressive therapy was discontinued and treatment with budesonide was initiated. Both baboons recovered and remained well on no medication until the end of follow-up (24 months).<br><br>CONCLUSIONS: Collagenous colitis has occasionally been reported in patients with organ transplants. It has been reported only once previously in baboons. The four cases reported here strongly suggest that 1) clinical features as well as histopathological findings of collagenous colitis in baboons are very similar to those in human patients; 2) it was associated with the immunocompromised state of the baboons, as two nonimmunosuppressed age-matched baboons in close proximity did not develop the condition; and 3) it may have had an infectious origin, as all four cases developed within a 4-week period of time.}, }
@article {pmid22291189, year = {2012}, author = {Yamanishi, H and Murakami, H and Ikeda, Y and Abe, M and Kumagi, T and Hiasa, Y and Matsuura, B and Onji, M}, title = {Regulatory dendritic cells pulsed with carbonic anhydrase I protect mice from colitis induced by CD4+CD25- T cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {188}, number = {5}, pages = {2164-2172}, doi = {10.4049/jimmunol.1100559}, pmid = {22291189}, issn = {1550-6606}, mesh = {Animals ; CD4-Positive T-Lymphocytes/enzymology/immunology/*transplantation ; Carbonic Anhydrase I/*metabolism/therapeutic use ; Cells, Cultured ; Coculture Techniques ; Colitis/enzymology/*immunology/*prevention &amp; control ; Dendritic Cells/*enzymology/*immunology/metabolism ; Disease Models, Animal ; Epitopes, T-Lymphocyte/administration &amp; dosage/immunology ; Female ; Forkhead Transcription Factors/biosynthesis/metabolism ; Immunophenotyping ; Interleukin-2 Receptor alpha Subunit/biosynthesis/deficiency ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; T-Lymphocytes, Regulatory/cytology/enzymology/immunology ; }, abstract = {Inflammatory bowel disease (IBD), which is characterized by a dysregulated intestinal immune response, is postulated to be controlled by intestinal self-antigens and bacterial Ags. Fecal extracts called cecal bacterial Ag (CBA) have been implicated in the pathogenesis of IBD. In this study, we identified a major protein of CBA related to the pathogenesis of IBD and established a therapeutic approach using Ag-pulsed regulatory dendritic cells (Reg-DCs). Using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry, carbonic anhydrase I (CA I) was identified as a major protein of CBA. Next, we induced colitis by transfer of CD4(+)CD25(-) T cells obtained from BALB/c mice into SCID mice. Mice were treated with CBA- or CA I-pulsed Reg-DCs (Reg-DCs(CBA) or Reg-DCs(CA1)), which expressed CD200 receptor 3 and produced high levels of IL-10. Treatment with Reg-DCs(CBA) and Reg-DCs(CA1) ameliorated colitis. This effect was shown to be Ag-specific based on no clinical response of irrelevant Ag (keyhole limpet hemocyanin)-pulsed Reg-DCs. Foxp3 mRNA expression was higher but RORγt mRNA expression was lower in the mesenteric lymph nodes (MLNs) of the Reg-DCs(CA1)-treated mice compared with those in the MLNs of control mice. In the MLNs, Reg-DCs(CA1)-treated mice had higher mRNA expression of IL-10 and TGF-β1 and lower IL-17 mRNA expression and protein production compared with those of control mice. In addition, Reg-DCs(CBA)-treated mice had higher Foxp3(+)CD4(+)CD25(+) and IL-10-producing regulatory T cell frequencies in MLNs. In conclusion, Reg-DCs(CA1) protected progression of colitis induced by CD4(+)CD25(-) T cell transfer in an Ag-specific manner by inducing the differentiation of regulatory T cells.}, }
@article {pmid22290405, year = {2012}, author = {Hamilton, MJ and Weingarden, AR and Sadowsky, MJ and Khoruts, A}, title = {Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection.}, journal = {The American journal of gastroenterology}, volume = {107}, number = {5}, pages = {761-767}, doi = {10.1038/ajg.2011.482}, pmid = {22290405}, issn = {1572-0241}, support = {R21AI091907/AI/NIAID NIH HHS/United States ; }, mesh = {*Clostridioides difficile ; Colon/*microbiology ; Enterocolitis, Pseudomembranous/complications/*therapy ; Feces/*microbiology ; Female ; Freezing ; Humans ; Inflammatory Bowel Diseases/complications ; Male ; Middle Aged ; Recurrence ; Tissue Donors ; }, abstract = {OBJECTIVES: While fecal microbiota transplantation (FMT) is historically known to be an effective means to treat recurrent Clostridium difficile infection (CDI) refractory to standard antibiotic therapies, the procedure is rarely performed. At least some of the reasons for limited availability are those of practicality, including aesthetic concerns and costs of donor screening. The objective of this study was to overcome these barriers in our clinical FMT program.<br><br>METHODS: We report clinical experience with 43 consecutive patients who were treated with FMT for recurrent CDI since inception of this program at the University of Minnesota. During this time, we simplified donor identification and screening by moving from patient-identified individual donors to standard volunteer donors. Material preparation shifted from the endoscopy suite to a standardized process in the laboratory, and ultimately to banking frozen processed fecal material that is ready to use when needed.<br><br>RESULTS: Standardization of material preparation significantly simplified the practical aspects of FMT without loss of apparent efficacy in clearing recurrent CDI. Approximately 30% of the patients had underlying inflammatory bowel disease, and FMT was equally effective in this group.<br><br>CONCLUSIONS: Several key steps in the standardization of donor material preparation significantly simplified the clinical practice of FMT for recurrent CDI in patients failing antibiotic therapy.}, }
@article {pmid22271132, year = {2012}, author = {Kassam, Z and Hundal, R and Marshall, JK and Lee, CH}, title = {Fecal transplant via retention enema for refractory or recurrent Clostridium difficile infection.}, journal = {Archives of internal medicine}, volume = {172}, number = {2}, pages = {191-193}, doi = {10.1001/archinte.172.2.191}, pmid = {22271132}, issn = {1538-3679}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Clostridioides difficile ; Diarrhea/microbiology/therapy ; Drug Resistance, Multiple, Bacterial ; Enema/*methods ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Middle Aged ; Secondary Prevention ; }, }
@article {pmid22260856, year = {2012}, author = {Kee, VR}, title = {Clostridium difficile infection in older adults: a review and update on its management.}, journal = {The American journal of geriatric pharmacotherapy}, volume = {10}, number = {1}, pages = {14-24}, doi = {10.1016/j.amjopharm.2011.12.004}, pmid = {22260856}, issn = {1876-7761}, mesh = {Aged ; Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/*adverse effects ; Anti-Infective Agents/*therapeutic use ; *Clostridioides difficile ; Clostridium Infections/chemically induced/diagnosis/*drug therapy ; Diarrhea/*microbiology ; Enterocolitis, Pseudomembranous/*drug therapy ; Fidaxomicin ; Humans ; Infection Control/methods ; Metronidazole/therapeutic use ; Risk Factors ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Clostridium difficile is a main cause of health care-associated infections. The incidence and severity have been increasing. Elderly persons are at an increased risk of morbidity and mortality from C. difficile infection (CDI). Relatively few advances have been made in the treatment of CDI since it was first identified as a cause of antibiotic-associated diarrhea more than 30 years ago.<br><br>OBJECTIVE: This article reviews CDI and provides an update on its treatment, including recently published clinical practice guidelines and the recently approved drug, fidaxomicin.<br><br>METHODS: English-language literature was identified through a search of PubMed (1966-October 2011), Iowa Drug Information Service (1966-October 2011), and International Pharmaceutical Abstracts (1970-October 2011). Key search terms included Clostridium difficile, Clostridium infections, pseudomembranous colitis, antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, elderly, geriatric, epidemiology, microbiology, diagnosis, risk factors, treatment, drug therapy, vancomycin, metronidazole, and fidaxomicin.<br><br>RESULTS: Metronidazole and vancomycin remain the mainstays of CDI treatment. Current guidelines recommend oral metronidazole for initial mild to moderate episodes or first recurrence. Oral vancomycin is recommended for initial severe episodes, or first or second recurrence. Fidaxomicin was approved in 2011 for treatment of CDI, but its place in therapy has yet to be determined. Other antibiotics have been used with variable success. Saccharomyces boulardii is the only probiotic that has shown efficacy in CDI. Fecal transplants have been used successfully in some patients, but randomized studies are needed. Immune therapy with a vaccine and monoclonal antibodies is being studied in clinical trials.<br><br>CONCLUSIONS: Treatment of CDI is challenging due to the limited number of drugs that have proven to be effective, concerns about antibiotic resistance, and recurring disease. The recent approval of fidaxomicin provides a new alternative. Immune therapy will likely play a greater role in the future.}, }
@article {pmid22251469, year = {2012}, author = {Wu, ZW and Ling, ZX and Lu, HF and Zuo, J and Sheng, JF and Zheng, SS and Li, LJ}, title = {Changes of gut bacteria and immune parameters in liver transplant recipients.}, journal = {Hepatobiliary &amp; pancreatic diseases international : HBPD INT}, volume = {11}, number = {1}, pages = {40-50}, doi = {10.1016/s1499-3872(11)60124-0}, pmid = {22251469}, issn = {1499-3872}, mesh = {Adult ; Analysis of Variance ; Bacteria/genetics/growth &amp; development/immunology/*isolation &amp; purification ; Biomarkers/blood ; Case-Control Studies ; China ; Endotoxins/blood ; Feces/chemistry/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Immunoglobulin A, Secretory/metabolism ; Inflammation Mediators/*blood ; Interleukin-6/blood ; Liver Transplantation/*immunology ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha/blood ; Young Adult ; }, abstract = {BACKGROUND: Liver transplantation is one of the most effective therapeutic options for patients with end-stage liver diseases, and gut microbiota is actively involved in potential infections in pretransplant and posttransplant patients. However, the diversity of gut microbiota and its relationship with the immune parameter of liver transplantation recipients are not well understood.<br><br>METHODS: We collected fresh feces and blood samples from 190 participants in China from November 2004 to May 2008, including 28 healthy volunteers, 51 cirrhotic patients and 111 liver-transplanted patients. Six interesting gut bacteria, plasma endotoxin, serum cytokines (i.e., tumor necrosis factor alpha and interleukin-6) and fecal secretory IgA (SIgA) were investigated by real-time quantitative PCR, chromogenic limulus amoebocyte assay, sandwich-type enzyme-linked immunosorbent assay and radioimmunoassay, respectively.<br><br>RESULTS: All Eubacteria, Bifidobacterium spp., Faecalibacterium prausnitzii and Lactobacillus spp. were significantly lower in the liver transplantation recipients while Enterobacteriaceae and Enterococcus spp. were significantly higher (P<0.05). Except for Enterococcus spp., other bacteria showed a tendency to restore to normal level along with the time after liver transplantation. Plasma endotoxin, interleukin-6 and fecal SIgA in cirrhotic patients increased significantly, but not in liver transplantation recipients. Plasma endotoxin and interleukin-6 were negatively correlated with all Eubacteria and the Bacteroides-Prevotella group, while tumor necrosis factor alpha was not significantly correlated with these six gut bacteria in cirrhotic patients.<br><br>CONCLUSIONS: Our study demonstrates that abundant gut bacteria were altered significantly in both cirrhotic and liver transplantation patients, while plasma endotoxin and interleukin-6 increased remarkably in cirrhotic patients, showing significant correlations with gut microbiota. Interestingly, our data show a tendency for these gut bacteria to restore to normal levels in liver transplantation recipients.}, }
@article {pmid22247151, year = {2012}, author = {Certad, G and Benamrouz, S and Guyot, K and Mouray, A and Chassat, T and Flament, N and Delhaes, L and Coiteux, V and Delaire, B and Praet, M and Cuvelier, C and Gosset, P and Dei-Cas, E and Creusy, C}, title = {Fulminant cryptosporidiosis after near-drowning: a human Cryptosporidium parvum strain implicated in invasive gastrointestinal adenocarcinoma and cholangiocarcinoma in an experimental model.}, journal = {Applied and environmental microbiology}, volume = {78}, number = {6}, pages = {1746-1751}, pmid = {22247151}, issn = {1098-5336}, mesh = {Adenocarcinoma/*parasitology ; Animals ; Cholangiocarcinoma/*parasitology ; Cryptosporidiosis/*diagnosis/pathology ; Cryptosporidium parvum/*isolation &amp; purification/*pathogenicity ; Disease Models, Animal ; Feces/parasitology ; France ; Humans ; Intestinal Neoplasms/*parasitology ; Mice ; Mice, SCID ; Near Drowning/*complications ; }, abstract = {In the present work, we report the characterization of a Cryptosporidium parvum strain isolated from a patient who nearly drowned in the Deule River (Lille, France) after being discharged from the hospital where he had undergone allogeneic stem cell transplantation. After being rescued and readmitted to the hospital, he developed fulminant cryptosporidiosis. The strain isolated from the patient's stools was identified as C. parvum II2A15G2R1 (subtype linked to zoonotic exposure) and inoculated into SCID mice. In this host, this virulent C. parvum isolate induced not only severe infection but also invasive gastrointestinal and biliary adenocarcinoma. The observation of adenocarcinomas that progressed through all layers of the digestive tract to the subserosa and spread via blood vessels confirmed the invasive nature of the neoplastic process. These results indicate for the first time that a human-derived C. parvum isolate is able to induce digestive cancer. This study is of special interest considering the exposure of a large number of humans and animals to this waterborne protozoan, which is highly tumorigenic when inoculated in a rodent model.}, }
@article {pmid24834192, year = {2012}, author = {Tahaei, SM and Mohebbi, SR and Zali, MR}, title = {Enteric hepatitis viruses.}, journal = {Gastroenterology and hepatology from bed to bench}, volume = {5}, number = {1}, pages = {7-15}, pmid = {24834192}, issn = {2008-2258}, abstract = {Hepatitis viruses are infectious agents that can infect liver and cause inflammation. The infection triggers immune response against infected cells that leads to the destruction of hepatic cells. This destruction has two consequences: leaking ALT and AST liver enzymes which increases during the course of disease and accumulation of bilirubin- a red pigmented compound released from dead red cells- which causes the yellow coloration of eyes and skin. These viruses transmit through diverse routes i.e. blood transfusion, sexual contacts and consuming water or food contaminated by feces. Enteric hepatitis viruses use the latter route for transmission; hence their outbreaks are more common in underdeveloped countries. There are currently two distinguished enteric hepatitis viruses, hepatitis A and hepatitis E. These viruses belong to different family of viruses and their epidemiological characteristics are different. These infections can be diagnosed by an ELISA for IgM antibody. A vaccine has been developed in last decade of twentieth century for hepatitis A virus, which is administered mostly in the developed world i.e. U.S and Japan. Treatment for these infections is mostly supportive; however, in the case of fulminant hepatitis the liver transplantation might be necessary.}, }
@article {pmid22183182, year = {2011}, author = {Borody, TJ and Khoruts, A}, title = {Fecal microbiota transplantation and emerging applications.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {9}, number = {2}, pages = {88-96}, pmid = {22183182}, issn = {1759-5053}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/*drug effects ; Clostridium Infections/drug therapy/*microbiology ; Colon/*microbiology ; Feces/*microbiology ; Humans ; *Metagenome ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has been utilized sporadically for over 50 years. In the past few years, Clostridium difficile infection (CDI) epidemics in the USA and Europe have resulted in the increased use of FMT, given its high efficacy in eradicating CDI and associated symptoms. As more patients request treatment and more clinics incorporate FMT into their treatment repertoire, reports of applications outside of CDI are emerging, paving the way for the use of FMT in several idiopathic conditions. Interest in this therapy has largely been driven by new research into the gut microbiota, which is now beginning to be appreciated as a microbial human organ with important roles in immunity and energy metabolism. This new paradigm raises the possibility that many diseases result, at least partially, from microbiota-related dysfunction. This understanding invites the investigation of FMT for several disorders, including IBD, IBS, the metabolic syndrome, neurodevelopmental disorders, autoimmune diseases and allergic diseases, among others. The field of microbiota-related disorders is currently in its infancy; it certainly is an exciting time in the burgeoning science of FMT and we expect to see new and previously unexpected applications in the near future. Well-designed and well-executed randomized trials are now needed to further define these microbiota-related conditions.}, }
@article {pmid22157239, year = {2012}, author = {Kelly, CR and de Leon, L and Jasutkar, N}, title = {Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results.}, journal = {Journal of clinical gastroenterology}, volume = {46}, number = {2}, pages = {145-149}, doi = {10.1097/MCG.0b013e318234570b}, pmid = {22157239}, issn = {1539-2031}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Clostridioides difficile ; Clostridium Infections/*prevention &amp; control/therapy ; *Colonoscopy/adverse effects ; Diarrhea/microbiology/prevention &amp; control/therapy ; Enterocolitis, Pseudomembranous/microbiology/*prevention &amp; control/therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Metagenome/*physiology ; Middle Aged ; Secondary Prevention ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {GOALS: We aim to present a data detailing our success with fecal microbiota transplantation (FMT) and to provide a simple treatment protocol.<br><br>BACKGROUND: Relapse is a common problem in patients treated for Clostridium difficile infection, often requiring prolonged courses of oral vancomycin with limited alternative treatment options. Administration of the entire fecal flora from a healthy individual to restore beneficial physiological species is referred to as FMT (also termed fecal bacteriotherapy or stool transplant). Although introduced over 50 years ago with high cure rates in published case series, FMT is neither routine practice nor widely available to patients.<br><br>STUDY: Twenty-six patients with relapsing C. difficile infection underwent FMT over a 28-month period. FMT was performed during colonoscopy by direct infusion of minimally processed donor stool.<br><br>RESULTS: Twenty-four female and 2 male patients underwent FMT. The mean duration of CDI was 12.6 months (range, 4 to 84 mo) before FMT. These patients have been followed for a mean duration of 10.7 months (range, 2 to 30 mo). Twenty-four patients have remained free of significant diarrhea or CDI. One experienced loose stool and resumed vancomycin despite remaining C. difficile negative; she developed CDI recurrence 11 months post-FMT after taking cephalexin. Another had diarrhea 2 months post-FMT. Stool was not tested for C. difficile; she received 1 week of vancomycin and CDI did not recur after this.<br><br>CONCLUSIONS: FMT through colonoscopy was simple, safe, and 92% effective in preventing further diarrhea or CDI relapse in this group of 26 patients with recurrent CDI.}, }
@article {pmid22156875, year = {2012}, author = {Zbar, AP and Khaikin, M}, title = {Should we care about the internal anal sphincter?.}, journal = {Diseases of the colon and rectum}, volume = {55}, number = {1}, pages = {105-108}, doi = {10.1097/DCR.0b013e318235b645}, pmid = {22156875}, issn = {1530-0358}, mesh = {Anal Canal/anatomy &amp; histology/physiology/*surgery ; Digestive System Surgical Procedures/*methods ; Fecal Incontinence/etiology/*prevention &amp; control ; Humans ; Postoperative Complications/*prevention &amp; control ; Rectal Fistula/surgery ; Rectum/*surgery ; }, abstract = {The internal anal sphincter is currently regarded as a significant contributor to continence function. Four physiological and morphological aspects of the internal anal sphincter are presented as part of the current evidence base for its preservation in anal surgery. 1) The incidence of continence disturbance following deliberate internal anal sphincterotomy is underestimated, although there is presently no prospective imaging or physiologic data supporting the selective use of sphincter-sparing surgical alternatives. 2) Given that the resting pressure is a measure of internal anal sphincter function, its physiologic representation (the rectoanal inhibitory reflex) shows inherent differences between incontinent and normal cohorts which suggest that internal anal sphincter properties act as a continence defense mechanism. 3) Anatomical differences in distal external anal sphincter overlap at the point of internal anal sphincter termination may preclude internal anal sphincter division in some patients where the distal anal canal will be unsupported following deliberate internal anal sphincterotomy. 4) internal anal sphincter-preservation techniques in fistula surgery may potentially safeguard postoperative function. Prospective, randomized trials using preoperative sphincter imaging and physiologic parameters of the rectoanal inhibitory reflex are required to shape surgical decision making in minor anorectal surgery in an effort to define whether alternatives to internal anal sphincter division lead to better functional outcomes.}, }
@article {pmid22155369, year = {2012}, author = {Mattila, E and Uusitalo-Seppälä, R and Wuorela, M and Lehtola, L and Nurmi, H and Ristikankare, M and Moilanen, V and Salminen, K and Seppälä, M and Mattila, PS and Anttila, VJ and Arkkila, P}, title = {Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection.}, journal = {Gastroenterology}, volume = {142}, number = {3}, pages = {490-496}, doi = {10.1053/j.gastro.2011.11.037}, pmid = {22155369}, issn = {1528-0012}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*pathogenicity ; *Colonoscopy/adverse effects/mortality ; Enterocolitis, Pseudomembranous/microbiology/mortality/*therapy ; Feces/*microbiology ; Female ; Finland ; Humans ; Male ; Middle Aged ; Polyethylene Glycols/administration &amp; dosage ; Recurrence ; Retrospective Studies ; Therapeutic Irrigation ; Time Factors ; Treatment Outcome ; Virulence ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: Treatment of recurrent Clostridium difficile infection (CDI) with antibiotics leads to recurrences in up to 50% of patients. We investigated the efficacy of fecal transplantation in treatment of recurrent CDI.<br><br>METHODS: We reviewed records from 70 patients with recurrent CDI who had undergone fecal transplantation. Fecal transplantation was performed at colonoscopy by infusing fresh donor feces into cecum. Before transplantation, the patients had whole-bowel lavage with polyethylene glycol solution. Clinical failure was defined as persistent or recurrent symptoms and signs, and a need for new therapy.<br><br>RESULTS: During the first 12 weeks after fecal transplantation, symptoms resolved in all patients who did not have strain 027 C difficile infections. Of 36 patients with 027 C difficile infection, 32 (89%) had a favorable response; all 4 nonresponders had a pre-existing serious condition, caused by a long-lasting diarrheal disease or comorbidity and subsequently died of colitis. During the first year after transplantation, 4 patients with an initial favorable response had a relapse after receiving antibiotics for unrelated causes; 2 were treated successfully with another fecal transplantation and 2 with antibiotics for CDI. Ten patients died of unrelated illnesses within 1 year after transplantation. No immediate complications of fecal transplantation were observed.<br><br>CONCLUSIONS: Fecal transplantation through colonoscopy seems to be an effective treatment for recurrent CDI and also for recurrent CDI caused by the virulent C difficile 027 strain.}, }
@article {pmid22150996, year = {2012}, author = {Ris, F and Colin, JF and Chilcott, M and Remue, C and Jamart, J and Kartheuser, A}, title = {Altemeier's procedure for rectal prolapse: analysis of long-term outcome in 60 patients.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {14}, number = {9}, pages = {1106-1111}, doi = {10.1111/j.1463-1318.2011.02904.x}, pmid = {22150996}, issn = {1463-1318}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anal Canal/surgery ; Cohort Studies ; Colon, Sigmoid/*surgery ; Digestive System Surgical Procedures/adverse effects/*methods ; Fecal Incontinence/etiology ; Female ; Humans ; Male ; Manometry ; Middle Aged ; Prospective Studies ; Rectal Prolapse/*surgery ; Rectum/*surgery ; Recurrence ; Treatment Outcome ; }, abstract = {AIM: Altemeier's procedure (perineal rectosigmoidectomy) is the operation of choice for rectal prolapse in the elderly. The aims of this prospective observational study were to evaluate its long-term actuarial recurrence risk and the influence of the length of rectosigmoid resection and associated levatorplasty on recurrence rate and continence.<br><br>METHOD: The perioperative and long-term data for all patients undergoing Altemeier's procedure since 1992 were analysed with regard to mortality, morbidity, continence, anorectal function and recurrence rate.<br><br>RESULTS: Sixty patients [median age 77 years (35-98)] underwent rectosigmoid resection [median length of bowel 14 (6-60) cm] with associated levatorplasty in 21 (35%). Overall mortality and morbidity were 1.6 and 11.6%, respectively. Manometry showed increased anal sphincter basal pressure and maximal squeeze pressure. We observed a decrease in postoperative rectal compliance (P=0.002). Age, gender, prolapse duration before surgery, levatorplasty and length of resection had no statistically significant relationship with recurrence. Continence improved in 62% and was stable over a median follow-up of 48 (1-186) months. Continence was positively related to a short length of bowel resection, but not to decreased rectal compliance. Actuarial recurrence was 14% at 4 years.<br><br>CONCLUSION: The long-term recurrence rate after the Altemeier procedure was low and not linked to resection length or to levatorplasty. Improvement in continence was stable over time.}, }
@article {pmid22138845, year = {2012}, author = {Takenaka, H and Ohmiya, N and Hirooka, Y and Nakamura, M and Ohno, E and Miyahara, R and Kawashima, H and Itoh, A and Watanabe, O and Ando, T and Goto, H}, title = {Endoscopic and imaging findings in protein-losing enteropathy.}, journal = {Journal of clinical gastroenterology}, volume = {46}, number = {7}, pages = {575-580}, doi = {10.1097/MCG.0b013e31823832ac}, pmid = {22138845}, issn = {1539-2031}, mesh = {Adolescent ; Adult ; Aged ; Capsule Endoscopes ; Capsule Endoscopy/*methods ; Colonoscopy/methods ; Double-Balloon Enteroscopy/*methods ; Endoscopy, Digestive System/methods ; Endoscopy, Gastrointestinal/methods ; Female ; Fluoroscopy/*methods ; Humans ; Intestine, Small/pathology ; Male ; Middle Aged ; Prognosis ; Protein-Losing Enteropathies/*diagnosis/*pathology ; Young Adult ; }, abstract = {OBJECTIVES: Protein-losing enteropathy (PLE) is often difficult to diagnose. We evaluated the diagnostic yields of underlying diseases of PLE among esophagogastroduodenoscopy, colonoscopy, fluoroscopic conventional enteroclysis (FCE), videocapsule endoscopy (VCE), and double-balloon enteroscopy (DBE) and prognosis after treatment.<br><br>METHODS: Between June 2003 and August 2010, 25 consecutive patients with PLE confirmed by fecal &#x3b1;1-antitrypsin clearance (n=18) and technetium 99m human serum albumin scintigraphy (n=19) were enrolled, investigated, and treated.<br><br>RESULTS: Of 25 patients, 4 (16%) with intestinal lymphangiectasia secondary to macroglobulinemia (n=1), amyloidosis (n=2), and strongyloidiasis (n=1) were diagnosed at preceding esophagogastroduodenoscopy or colonoscopy, and 7 (32%) with primary intestinal lymphangiectasia and chronic nonspecific multiple ulcers unrelated to nonsteroidal anti-inflammatory drugs of the small intestine were newly diagnosed at FCE or VCE. Other 11 (44%) patients with primary intestinal lymphangiectasia, small-bowel tumors, amyloidosis, chronic nonspecific multiple ulcers unrelated to nonsteroidal anti-inflammatory drugs of the small intestine, Crohn's disease, and small-bowel ulcers due to polyarteritis nodosa were diagnosed only at DBE with biopsy. Three patients with primary intestinal lymphangiectasia, cirrhosis after living donor liver transplantation, and congestive heart failure were not diagnosed at any small-bowel examination. The overall diagnostic yield of FCE, VCE, and DBE was 62% (8/13), 83% (14/17), and 88% (22/25), respectively. Eight patients (32%) died of underlying disorders regardless of medical treatment over the follow-up period.<br><br>CONCLUSIONS: DBE with pathologic findings of biopsy specimens was useful for the differential diagnosis of PLE. Noninvasive VCE might be preferable and useful for screening and follow up of PLE without stricture. Prognosis of a subgroup of PLE was poor regardless of treatment.}, }
@article {pmid22134217, year = {2012}, author = {Lo Vecchio, A and Zacur, GM}, title = {Clostridium difficile infection: an update on epidemiology, risk factors, and therapeutic options.}, journal = {Current opinion in gastroenterology}, volume = {28}, number = {1}, pages = {1-9}, doi = {10.1097/MOG.0b013e32834bc9a9}, pmid = {22134217}, issn = {1531-7056}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridioides difficile/isolation &amp; purification/*pathogenicity ; *Clostridium Infections/drug therapy/epidemiology/microbiology ; *Enterocolitis, Pseudomembranous/drug therapy/epidemiology/microbiology ; Humans ; Incidence ; Intestines/*microbiology ; Risk Factors ; United States/epidemiology ; }, abstract = {PURPOSE OF REVIEW: The incidence and severity of Clostridium difficile infection (CDI) around the world has increased over the past 20 years due to the emergence of hypervirulent strains, increased use and misuse of antibiotics, and the increase of susceptible at-risk populations. Treatments currently available for CDI are inadequate to impede the increasing spread and virulence of the infection, avoid recurrence in chronic patients or prevent infection in at-risk populations.<br><br>RECENT FINDINGS: New and promising evidence has been presented during the past year, focusing on two major points: preservation of gut microflora and optimization of immune response to CDI and toxins.<br><br>SUMMARY: The review aims to summarize the most recent evidence available on the epidemiology, risk factors and treatment of CDI. New antibiotics with selected action on C. difficile and limited effect on microflora (fidaxomicin) and donor fecal transplantation seem to have a relevant efficacy in treating CDI and reducing its recurrence. The use of selected monoclonal antibodies directed against C. difficile toxins in addition to standard therapy is a new, promising approach for the treatment of recurrent cases. Vaccination could be an additional weapon against CDI. New robust data are needed before recommendations can be made to abandon current treatment based on vancomycin and metronidazole and move toward new frontiers.}, }
@article {pmid22122559, year = {2012}, author = {Hunter, JP and Saratzis, A and Froggatt, P and Harmston, C}, title = {Effect of season and ambient temperature on outcome of guaiac-based faecal occult blood tests performed for colorectal cancer screening.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {14}, number = {9}, pages = {1084-1089}, doi = {10.1111/j.1463-1318.2011.02900.x}, pmid = {22122559}, issn = {1463-1318}, mesh = {Colorectal Neoplasms/*diagnosis ; Early Detection of Cancer/methods ; Female ; Guaiac ; Humans ; *Indicators and Reagents ; Male ; Middle Aged ; *Occult Blood ; Reproducibility of Results ; *Seasons ; *Temperature ; Weather ; }, abstract = {AIM: Guaiac-based faecal occult blood tests (gFOBTs) are used in the colorectal cancer screening programme. Recent data suggested that the immunological faecal occult blood test illustrated a variation in positivity according to season and ambient temperature. Our aim was to assess the effect of season and ambient temperature on the positivity rates of the gFOBT during pilot screening for colorectal cancer.<br><br>METHOD: Data from the first year of round 1 of the pilot screening programme in Coventry and Warwickshire were analysed. Patients with positive and negative gFOBT samples were included. Patients with spoilt samples or incomplete data were excluded. Of the total of 59513 patients, 30311 were men and 29202 women. Mean age was 56 years. Daily temperature data were provided by the meteorological office.<br><br>RESULTS: Median exposure of the gFOBT test card was 6 days (range 1-17). Median daily maximum temperature was 14&#xb0;C. Spring and summer illustrated significantly decreased positivity rates compared with autumn and winter (Pearson's chi-squared test, P<0.001). Mean daily maximum temperature for the test card exposure showed no significant difference in positivity rates (P=0.53). Subgroup analysis revealed a significant reduction in positive samples in the >25&#xb0;C subgroup (P=0.045).<br><br>CONCLUSIONS: There is a seasonal variation in positivity rates of gFOBTs with increased positivity in spring and summer months. There is no difference in positivity rates in relation to ambient temperature except in subgroup analysis where there is a significant reduction in positivity rates above 25&#xb0;C.}, }
@article {pmid22096580, year = {2011}, author = {Wunderli, W and Meerbach, A and Güngör, T and Berger, C and Greiner, O and Caduff, R and Trkola, A and Bossart, W and Gerlach, D and Schibler, M and Cordey, S and McKee, TA and Van Belle, S and Kaiser, L and Tapparel, C}, title = {Astrovirus infection in hospitalized infants with severe combined immunodeficiency after allogeneic hematopoietic stem cell transplantation.}, journal = {PloS one}, volume = {6}, number = {11}, pages = {e27483}, pmid = {22096580}, issn = {1932-6203}, mesh = {Astroviridae Infections/*diagnosis/mortality/*virology ; Caco-2 Cells ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Infant ; Male ; RNA, Viral/genetics ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Severe Combined Immunodeficiency/mortality/therapy/*virology ; Transplantation, Homologous/*adverse effects ; }, abstract = {Infants with severe primary combined immunodeficiency (SCID) and children post-allogeneic hematopoietic stem cell transplantation (HSCT) are extremely susceptible to unusual infections. The lack of generic tools to detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period. Analysis was undertaken by combining cell culture, electron microscopy and sequence-independent single primer amplification (SISPA) techniques. Caco-2 cells inoculated with fecal samples developed a cytopathic effect and non-enveloped viral particles in infected cells were detected by electron microscopy. SISPA led to the identification of astrovirus as the pathogen. Both sequencing of the capsid gene and the pattern of infection suggested nosocomial transmission from a chronically excreting index case to 2 other patients leading to fatal infection in 1 and to transient disease in the others. Virus-specific, real-time reverse transcription polymerase chain reaction was then performed on different stored samples to assess the extent of infection. Infection was associated with viremia in 2 cases and contributed to death in 1. At autopsy, viral RNA was detected in the brain and different other organs, while immunochemistry confirmed infection of gastrointestinal tissues. This report illustrates the usefulness of the combined use of classical virology procedures and modern molecular tools for the diagnosis of unexpected infections. It illustrates that astrovirus has the potential to cause severe disseminated lethal infection in highly immunocompromised pediatric patients.}, }
@article {pmid22090724, year = {2011}, author = {Gucev, Z and Slavevska, N and Tasic, V and Laban, N and Pop-Jordanova, N and Danilovski, D and Woolf, J and Cole, D}, title = {Congenital erythropoietic porphyria with two mutations of the uroporphyrinogen III synthase gene (Cys73Arg, Thr228Met).}, journal = {Indian journal of human genetics}, volume = {17}, number = {2}, pages = {104-107}, pmid = {22090724}, issn = {0971-6866}, abstract = {Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of uroporphyrinogen III synthase (UROS). We describe a 14-year-old girl with red urine since infancy, progressive blistering and scarring of the skin, and moderate hemolytic anemia. After years of skin damage, her face is mutilated; she has a bald patch on the scalp, hypertrichosis of the neck, areas of skin darkening, and limited joint movements of the hands. Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. Sequencing of the UROS gene identified two mutations causing CEP (Cys73Arg, Thr228Met). The patient lesions are progressing. Bone marrow transplantation and/or gene therapy are proposed as the next steps in her treatment. In brief, we describe a CEP with confirmed two pathogenic mutations, severe phenotype and discuss the various treatment options available.}, }
@article {pmid22054124, year = {2011}, author = {Emmanouilidis, N and Jäger, MD and Winkler, M and Klempnauer, J}, title = {Boerhaave syndrome as a complication of colonoscopy preparation: a case report.}, journal = {Journal of medical case reports}, volume = {5}, number = {}, pages = {544}, pmid = {22054124}, issn = {1752-1947}, abstract = {INTRODUCTION: Colonoscopy is one of the most frequently performed elective and invasive diagnostic interventions. For every colonoscopy, complete colon preparation is mandatory to provide the best possible endoluminal visibility; for example, the patient has to drink a great volume of a non-resorbable solution to flush out all feces. Despite the known possible nauseating side effects of colonoscopy preparation and despite the knowledge that excessive vomiting can cause rupture of the distal esophagus (Boerhaave syndrome), which is a rare but severe complication with high morbidity and mortality, it is not yet a standard procedure to provide a patient with an anti-emetic medication during a colon preparation process. This is the first report of Boerhaave syndrome induced by colonoscopy preparation, and this case strongly suggests that the prospect of being at risk of a severe complication connected with an elective colonoscopy justifies a non-invasive, inexpensive yet effective precaution such as an anti-emetic co-medication during the colonoscopy preparation process.<br><br>CASE PRESENTATION: A 73-year-old Caucasian woman was scheduled to undergo elective colonoscopy. For the colonoscopy preparation at home she received commercially available bags containing soluble polyethylene glycol powder. No anti-emetic medication was prescribed. After drinking the prepared solution she had to vomit excessively and experienced a sudden and intense pain in her back. An immediate computed tomography (CT) scan revealed a rupture of the distal esophagus (Boerhaave syndrome). After initial conservative treatment by endoluminal sponge vacuum therapy, she was taken to the operating theatre and the longitudinal esophageal rupture was closed by direct suture and gastric fundoplication (Nissen procedure). She recovered completely and was discharged three weeks after the initial event.<br><br>CONCLUSIONS: To the best of our knowledge, this is the first report of a case of Boerhaave syndrome as a complication of excessive vomiting caused by colonoscopy preparation. The case suggests that patients who are prepared for a colonoscopy by drinking large volumes of fluid should routinely receive an anti-emetic medication during the preparation process, especially when they have a tendency to nausea and vomiting.}, }
@article {pmid22029421, year = {2012}, author = {Rodriguez, B and Prioult, G and Hacini-Rachinel, F and Moine, D and Bruttin, A and Ngom-Bru, C and Labellie, C and Nicolis, I and Berger, B and Mercenier, A and Butel, MJ and Waligora-Dupriet, AJ}, title = {Infant gut microbiota is protective against cow's milk allergy in mice despite immature ileal T-cell response.}, journal = {FEMS microbiology ecology}, volume = {79}, number = {1}, pages = {192-202}, doi = {10.1111/j.1574-6941.2011.01207.x}, pmid = {22029421}, issn = {1574-6941}, mesh = {Animals ; Bacteroides/physiology ; Bifidobacterium/physiology ; Disease Models, Animal ; Feces/microbiology ; Gastrointestinal Tract ; Germ-Free Life ; Humans ; Ileum/immunology/*microbiology ; *Immunity, Cellular ; Immunoglobulin G/blood ; Infant ; Metagenome/*physiology ; Mice ; Mice, Inbred C3H ; Milk/*adverse effects ; Milk Hypersensitivity/immunology/*microbiology/prevention &amp; control ; T-Lymphocytes/immunology ; T-Lymphocytes, Regulatory ; }, abstract = {Faecal microbiota of healthy infant displays a large abundance of Bifidobacterium spp. and Bacteroides spp. Although some studies have reported an association between these two genera and allergy, these findings remain a subject of debate. Using a gnotobiotic mouse model of cow's milk allergy, we investigated the impact of an infant gut microbiota – mainly composed of Bifidobacterium and Bacteroides spp. – on immune activation and allergic manifestations. The transplanted microbiota failed to restore an ileal T-cell response similar to the one observed in conventional mice. This may be due to the low bacterial translocation into Peyer's patches in gnotobiotic mice. The allergic response was then monitored in germ-free, gnotobiotic, and conventional mice after repeated oral sensitization with whey proteins and cholera toxin. Colonized mice displayed a lower drop of rectal temperature upon oral challenge with b-lactoglobulin, lower plasma mMCP-1, and lower anti-BLG IgG1 than germ-free mice. The foxp3 gene was highly expressed in the ileum of both colonized mice that were protected against allergy. This study is the first demonstration that a transplanted healthy infant microbiota mainly composed of Bifidobacterium and Bacteroides had a protective impact on sensitization and food allergy in mice despite altered T-cell response in the ileum.}, }
@article {pmid22025588, year = {2011}, author = {Tseng, JJ and Lai, MS and Lin, MC and Fu, YC}, title = {Stool color card screening for biliary atresia.}, journal = {Pediatrics}, volume = {128}, number = {5}, pages = {e1209-15}, doi = {10.1542/peds.2010-3495}, pmid = {22025588}, issn = {1098-4275}, mesh = {Biliary Atresia/complications/*diagnosis/surgery ; Cohort Studies ; Color ; Databases, Factual ; *Feces ; Female ; Humans ; Infant, Newborn ; Jaundice, Neonatal/*diagnosis/etiology/surgery ; Male ; Neonatal Screening/*methods ; *Reagent Kits, Diagnostic ; Retrospective Studies ; Sensitivity and Specificity ; Taiwan ; }, abstract = {INTRODUCTION: Biliary atresia is a major cause of extrahepatic obstructive jaundice in neonates. Early Kasai operation is the gold standard of treatment. In this study, we evaluated the effectiveness of stool color card screening by using claims data from the National Health Insurance Research Database.<br><br>METHODS: This was a retrospective cohort study. Data from medical charts of all inpatients who were diagnosed with biliary atresia from 1996 to 2008 were collected from Taiwan's National Health Insurance Research Database. Patients who received a Kasai operation or liver transplant were identified by the Operation code. The patients' gender, age at admission, and type of operation were collected and analyzed.<br><br>RESULTS: From 1996 to 2008, the overall incidence of biliary atresia was 1.48 per 10,000 live births. The median age at first admission for patients with suspected biliary atresia decreased after the implementation of stool color card screening (47 vs 43 days). The proportion of very late referral decreased from 9.5% to 4.9%. The median age of Kasai operation advanced from 51 to 48 days. The proportions of Kasai operation within 60 days of age were 68.9% before and 73.6% after screening program.<br><br>CONCLUSION: Stool color card screening seemed to increase parents' and physicians' awareness of biliary atresia. It also was associated with a decline in the proportion of late referral. Thus, screening might be especially effective in areas with high a proportion of late referral. Improvements in the speed of workup and the operation room should be the focus of education and training in the future.}, }
@article {pmid22018255, year = {2011}, author = {Mongardini, M and Lisi, A and Giofrè, M and Ledda, M and Grimaldi, S and Scarnò, M and Trucchia, A and Kyriacou, KA and Badiali, D and Custureri, F}, title = {Human muscle-derived stem cells. Effectiveness in animal models of faecal incontinence. Research scheduling.}, journal = {Il Giornale di chirurgia}, volume = {32}, number = {8-9}, pages = {357-360}, pmid = {22018255}, issn = {0391-9005}, mesh = {Anal Canal/physiopathology/surgery ; Animals ; Cell Differentiation/drug effects ; Cells, Cultured/drug effects ; *Cord Blood Stem Cell Transplantation ; Dexamethasone/pharmacology ; Fecal Incontinence/*surgery ; Humans ; Hydrocortisone/pharmacology ; *Mesenchymal Stem Cell Transplantation ; Models, Animal ; Muscle Development/drug effects ; Muscle, Skeletal/cytology ; Rats ; Rats, Mutant Strains ; Rats, Wistar ; Regeneration ; Satellite Cells, Skeletal Muscle/physiology ; Severe Combined Immunodeficiency ; Transplantation, Heterologous ; }, abstract = {Researchers believe that human muscle-derived cells are able to restore leak-point pressure to normal levels by differentiating into new muscle fibres that prevent anal sphincter muscle atrophy. Laboratory data are needed to identify exactly how these cells work to regenerate muscle. The objective of this study is to test whether stem cells can be employed to treat internal anal sphincter (IAS) injuries in humans; to this end, this work will use a two-step process to study: first, the effectiveness of the treatment in a sample of animals with artificial injuries to the IAS and then to verify the results in a population of selected humans affected by pathology.}, }
@article {pmid22017691, year = {2011}, author = {Borody, TJ and Campbell, J}, title = {Fecal microbiota transplantation: current status and future directions.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {5}, number = {6}, pages = {653-655}, doi = {10.1586/egh.11.71}, pmid = {22017691}, issn = {1747-4132}, mesh = {Clostridioides difficile/isolation &amp; purification ; Colitis, Ulcerative/microbiology/*therapy ; Feces/*microbiology ; Humans ; *Metagenome ; Probiotics/therapeutic use ; Quality of Life ; Treatment Outcome ; }, }
@article {pmid22002980, year = {2011}, author = {Gough, E and Shaikh, H and Manges, AR}, title = {Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {53}, number = {10}, pages = {994-1002}, doi = {10.1093/cid/cir632}, pmid = {22002980}, issn = {1537-6591}, support = {CHM-94228//Canadian Institutes of Health Research/Canada ; }, mesh = {*Clostridioides difficile ; Clostridium Infections/*therapy ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Intestines/*microbiology ; Metagenome ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridium difficile infection (CDI) is a gastrointestinal disease believed to be causally related to perturbations to the intestinal microbiota. When standard treatment has failed, intestinal microbiota transplantation (IMT) is an alternative therapy for patients with CDI. IMT involves infusing intestinal microorganisms (in a suspension of healthy donor stool) into the intestine of a sick patient to restore the microbiota. However, protocols and reported efficacy for IMT vary. We conducted a systematic literature review of IMT treatment for recurrent CDI and pseudomembranous colitis. In 317 patients treated across 27 case series and reports, IMT was highly effective, showing disease resolution in 92% of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of IMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better designed studies are conducted to confirm best practices.}, }
@article {pmid21992958, year = {2011}, author = {Floch, MH and Walker, WA and Madsen, K and Sanders, ME and Macfarlane, GT and Flint, HJ and Dieleman, LA and Ringel, Y and Guandalini, S and Kelly, CP and Brandt, LJ}, title = {Recommendations for probiotic use-2011 update.}, journal = {Journal of clinical gastroenterology}, volume = {45 Suppl}, number = {}, pages = {S168-71}, doi = {10.1097/MCG.0b013e318230928b}, pmid = {21992958}, issn = {1539-2031}, support = {93675-1//Canadian Institutes of Health Research/Canada ; }, mesh = {Diarrhea/therapy ; Enema ; Enterocolitis, Necrotizing/therapy ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; Inflammatory Bowel Diseases/therapy ; Probiotics/*therapeutic use ; }, abstract = {This study describes the consensus opinion of the participants of the third Yale Workshop on probiotic use. There were 10 experts participating. The recommendations update those of the first 2 meetings that were published in 2005 and 2008. The workshop presentations and papers in this supplement relate to the involvement of normal microbiota involved in intestinal microecology, how the microbes interact with the intestine to affect our immunologic responses, the stability and natural history of probiotic organisms, and the role of the intestinal microbatome with regard to affecting cardiac risk factors and obesity. Recommendations for the use of probiotics in necrotizing enterocolitis, childhood diarrhea, inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile diarrhea are reviewed. As in previous publications, the recommendations are given as A, B, or C ratings. The recent positive experiences with bacteriotherapy (fecal microbiome transplant) are also discussed in detail and a positive recommendation is made for use in severe resistant C. difficile diarrhea.}, }
@article {pmid21992957, year = {2011}, author = {Brandt, LJ and Reddy, SS}, title = {Fecal microbiota transplantation for recurrent clostridium difficile infection.}, journal = {Journal of clinical gastroenterology}, volume = {45 Suppl}, number = {}, pages = {S159-67}, doi = {10.1097/MCG.0b013e318222e603}, pmid = {21992957}, issn = {1539-2031}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/therapeutic use ; Child, Preschool ; Clostridioides difficile/*drug effects ; Clostridium Infections/microbiology/*therapy ; Colon/microbiology ; Enema/*methods ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Metagenome/*physiology ; Middle Aged ; Secondary Prevention ; Treatment Outcome ; }, abstract = {With the increasing prevalence of recurrent/refractory Clostridium difficile infection (CDI), alternative treatments to the standard antibiotic therapies are being sought. One of the more controversial of such alternative treatments is fecal microbiota transplantation (FMT). Although the notion of FMT is foreign-even startling-and not esthetic to most people, the concept has been around for many decades. Its benefit and efficacy dates back >50 years to its use for staphylococcal pseudomembranous colitis, and now FMT is showing a great promise as an inexpensive, safe, and highly efficient treatment for recurrent and refractory CDI. Moreover, with a better understanding of the intricacies of the colonic microbiome and its role in colonic pathophysiology, FMT has the potential to become the standard of care for CDI treatment, and a potential answer to other intestinal disorders in years to come.}, }
@article {pmid21984595, year = {2012}, author = {Sanoh, S and Nozaki, K and Murai, H and Terashita, S and Teramura, T and Ohta, S}, title = {Prediction of human metabolism of FK3453 by aldehyde oxidase using chimeric mice transplanted with human or rat hepatocytes.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {40}, number = {1}, pages = {76-82}, doi = {10.1124/dmd.111.041954}, pmid = {21984595}, issn = {1521-009X}, mesh = {Aldehyde Oxidase/*metabolism ; Animals ; Child, Preschool ; Hepatocytes/*metabolism/*transplantation ; Humans ; Male ; Mice ; Predictive Value of Tests ; Protein Binding/genetics ; Pyridazines/*metabolism ; Pyrimidines/*metabolism ; Radiation Chimera ; Rats ; Rats, Sprague-Dawley ; Species Specificity ; }, abstract = {During drug development, it is important to predict the activities of multiple metabolic enzymes, not only cytochrome P450 (P450) but also non-P450 enzymes, such as conjugative enzymes and aldehyde oxidase (AO). In this study, we focused on prediction of AO-mediated human metabolism and pharmacokinetics (PK) of 6-(2-amino-4-phenylpyrimidine-5-yl)-2-isopropylpyridazin-3(2H)-one (FK3453) (Astellas Pharma Inc.), the development of which was suspended due to extremely low exposure in human, despite good oral bioavailability in rat and dog. We examined species difference in oxidative metabolism of the aminopyrimidine moiety of FK3453, catalyzed by AO, using human-chimeric mice with humanized liver (h-PXB mice) and rat-chimeric mice (r-PXB mice) transplanted with rat hepatocytes. AO activity of h-PXB mouse hepatocytes was higher than that of r-PXB mouse hepatocytes. Moreover, higher concentrations of human-specific AO-generated FK3453 metabolite A-M were detected in urine and feces after administration of FK3453 to h-PXB mice versus r-PXB mice. The total clearance of h-PXB mice was 2-fold higher than that of r-PXB mice. These results agreed reasonably well with the metabolism and PK profiles of FK3453 in human and rat. Our results indicated that h-PXB mice should be helpful for predicting the metabolic profile of drugs in humans, and the use of both h-PXB and r-PXB mice should be helpful for evaluation of species differences of AO metabolic activity.}, }
@article {pmid21965156, year = {2012}, author = {Wu, ZW and Lu, HF and Wu, J and Zuo, J and Chen, P and Sheng, JF and Zheng, SS and Li, LJ}, title = {Assessment of the fecal lactobacilli population in patients with hepatitis B virus-related decompensated cirrhosis and hepatitis B cirrhosis treated with liver transplant.}, journal = {Microbial ecology}, volume = {63}, number = {4}, pages = {929-937}, pmid = {21965156}, issn = {1432-184X}, mesh = {DNA, Bacterial/analysis/genetics/isolation &amp; purification ; Feces/*microbiology ; Hepatitis B/*complications/virology ; Hepatitis B virus ; Humans ; Lactobacillus/classification/genetics/*isolation &amp; purification ; Liver Cirrhosis/*therapy/virology ; *Liver Transplantation ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics ; }, abstract = {This study aims to provide an overview of the diversity of intestinal Lactobacillus among Chinese patients with hepatitis B virus (HBV)-related decompensated cirrhosis and who received liver transplant for hepatitis B cirrhosis. Fecal samples were collected from 38 healthy volunteers, 61 patients with HBV-related decompensated cirrhosis (group LC) and 74 patients who had liver transplant for hepatitis B cirrhosis (group LT). Quantitative polymerase chain reaction technology with species-specific primers was applied to investigate lactobacilli 16S rDNA in crude DNA, extracted from fecal samples. Software package Statistical Package for the Social Sciences and Palaeontological Statistics for Windows was used to analyze the data. Lactobacilli population of the two patient groups was different from the healthy control subjects, principal differences being marked decrease in the population of Lactobacillus rhamnosus (p < 0.001 for both patient groups) and reduction in the frequency of Lactobacillus fermentus (p < 0.001 for group LC and p < 0.01 for group LT). Our findings on the frequency of lactobacilli population suggested decreased diversity in groups LC and LT (compared with the healthy controls (p < 0.001 and p < 0.01, respectively)). Patients tended to have less complex fecal lactobacilli composition than the healthy controls, especially in the group LC.}, }
@article {pmid21943947, year = {2011}, author = {Fleshman, JW}, title = {Should we, not could we? A commentary on "Pyloric valve transposition as substitute for a colostomy in humans: a preliminary report".}, journal = {American journal of surgery}, volume = {202}, number = {4}, pages = {417-418}, doi = {10.1016/j.amjsurg.2011.07.003}, pmid = {21943947}, issn = {1879-1883}, mesh = {Anal Canal/*injuries ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Pylorus/*blood supply/*transplantation ; Wounds and Injuries/*surgery ; }, }
@article {pmid21943653, year = {2011}, author = {Lacarriere, E and Suaud, L and Caremel, R and Rouache, L and Tuech, JJ and Pfister, C}, title = {[Rectourethral fistulae: diagnosis and management. Review of the literature].}, journal = {Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie}, volume = {21}, number = {9}, pages = {585-594}, doi = {10.1016/j.purol.2011.06.008}, pmid = {21943653}, issn = {1166-7087}, mesh = {Algorithms ; Humans ; Rectal Fistula/*diagnosis/*surgery ; Risk Factors ; Urethral Diseases/*diagnosis/*surgery ; Urinary Fistula/*diagnosis/*surgery ; }, abstract = {INTRODUCTION: Rectourethral fistulae are predominantly of iatrogenous origin. They alter the patient's quality of life and are difficult to manage from a medical standpoint.<br><br>PATIENTS AND METHODS: The major series of patients of the last 20 years have been analyzed, in order to define the best management of rectourethral fistulae.<br><br>RESULTS: Many surgical techniques have been tried, as well as several protocols, ranging from simple urinary and fecal diversion to diversion followed by reconstruction and regional flap in case of tissue damage.<br><br>CONCLUSION: The fistula's cause and the use of radiotherapy had a major impact on its prognosis. The best-suited protocol was the 3-step protocol, which has been described within. The flap, which seemed to have the best results, was the gracilis muscle flap.}, }
@article {pmid21895924, year = {2012}, author = {de Zeeuw, S and Heikens, JT and Gooszen, HG and van Laarhoven, CJ}, title = {The ileo neo-rectal anastomosis in patients with familial adenomatous polyposis: a prospective case series with long-term follow up.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {14}, number = {7}, pages = {861-865}, doi = {10.1111/j.1463-1318.2011.02806.x}, pmid = {21895924}, issn = {1463-1318}, mesh = {Adenomatous Polyposis Coli/*surgery ; Adult ; Anal Canal/physiopathology ; Anastomosis, Surgical/methods ; Colectomy ; Defecation ; Fecal Incontinence/etiology ; Female ; Follow-Up Studies ; Humans ; Ileum/*surgery/transplantation ; Intestinal Mucosa/*transplantation ; Male ; Manometry ; Postoperative Complications/*etiology ; Prospective Studies ; *Quality of Life ; Rectum/physiopathology/*surgery ; Time Factors ; }, abstract = {AIM: In patients with familial adenomatous polyposis (FAP), removal of the colonic mucosa is essential to reduce the lifetime risk of developing cancer). For this purpose, ileo-pouch anal anastomosis (IPAA) has been the gold standard, but morbidity related to the dissection of the pelvis remains substantial. In an attempt to reduce the procedure-related complications of pelvic dissection, ileoneo-rectal anastomosis (INRA) has been developed. In this case series of FAP patients, the long-term functional results, morbidity and quality of life (QoL) of the INRA procedure were evaluated and compared with its early outcome.<br><br>METHOD: Long-term follow up of a consecutive group of eight FAP patients with an INRA procedure (between 1998 and 2005) was undertaken. Data on functional results, complications, manometry and endoscopy were recorded prospectively.<br><br>RESULTS: Eight patients with FAP underwent the INRA procedure. The median number of defaecations over 24 h was five. No pelvic sepsis or bladder dysfunction occurred. One patient, in whom concomitant Crohn's disease was diagnosed in retrospect, was converted to IPAA. In the INRA patients, no sexual dysfunction occurred. Endoscopic examination showed normal mucosa without any evidence of polyp formation.<br><br>CONCLUSION: Restorative surgery by means of the INRA procedure yields good functional results in FAP patients, without any pelvic dissection-related morbidity or regrowth of polyps in the neo-rectum.}, }
@article {pmid21892601, year = {2012}, author = {Chen, Z and Liu, G and Ye, Z and Kong, D and Yao, L and Guo, H and Yang, W and Yu, X}, title = {The construction of an oxalate-degrading intestinal stem cell population in mice: a potential new treatment option for patients with calcium oxalate calculus.}, journal = {Urological research}, volume = {40}, number = {2}, pages = {131-141}, pmid = {21892601}, issn = {1434-0879}, mesh = {Animals ; Calcium Oxalate/*metabolism ; *Cell- and Tissue-Based Therapy ; Cells, Cultured ; Embryonic Stem Cells/cytology/*metabolism/*transplantation ; Feces/microbiology ; Female ; Genes, Bacterial/genetics ; Humans ; Hyperoxaluria/complications/metabolism ; Intestinal Mucosa/*metabolism ; Intestines/cytology/embryology ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Models, Animal ; Oxalobacter formigenes/genetics/isolation &amp; purification ; Plasmids/genetics ; Pregnancy ; Transfection ; Urinary Calculi/etiology/metabolism/*therapy ; }, abstract = {About 80% of all urological stones are calcium oxalate, mainly caused by idiopathic hyperoxaluria (IH). The increased absorption of oxalate from the intestine is the major factor underlying IH. The continuous self-renewal of the intestinal epithelium is due to the vigorous proliferation and differentiation of intestinal stem cells. If the intestinal stem cell population can acquire the ability to metabolize calcium oxalate by means of oxc and frc transgenes, this will prove a promising new therapy option for IH. In our research, the oxalate-degrading genes of Oxalobacter formigenes (Oxf)-the frc gene and oxc gene-were cloned and transfected into a cultured mouse-derived intestinal SC population to give the latter an oxalate-degrading function. Oxf was isolated and cultivated and the oxalate-degrading genes-frc and oxc-were cloned. The dicistronic eukaryotic expression vector pIRES-oxc-frc was constructed and transferred into the mouse stem cell population. After selection with G418, the expression of the genes was identified. The oxalate-degrading function of transfected cells was determined by transfection into the intestinal stem cell population of the mouse. The change in oxalate concentration was determined with an ion chromatograph. The recombinant plasmid containing oxc and frc genes was transfected into the stem cell population of the mouse and the expression of the genes found normal. The cell population had acquired an oxalate-degrading function. The oxc and frc genes could be transfected into the intestinal stem cell population of the mouse and the cells acquired an oxalate-degrading function.}, }
@article {pmid21873913, year = {2011}, author = {Colwell, JC and Ratliff, CR and Goldberg, M and Baharestani, MM and Bliss, DZ and Gray, M and Kennedy-Evans, KL and Logan, S and Black, JM}, title = {MASD part 3: peristomal moisture- associated dermatitis and periwound moisture-associated dermatitis: a consensus.}, journal = {Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society}, volume = {38}, number = {5}, pages = {541-53; quiz 554-5}, doi = {10.1097/WON.0b013e31822acd95}, pmid = {21873913}, issn = {1528-3976}, mesh = {Bandages ; Consensus ; Dermatitis, Irritant/*etiology/physiopathology/therapy ; Evidence-Based Medicine ; Fecal Incontinence/complications ; Female ; Follow-Up Studies ; Humans ; Humidity/*adverse effects ; Male ; Practice Guidelines as Topic ; Risk Assessment ; Skin Care/*methods ; Skin Transplantation/methods ; Surgical Stomas/*adverse effects ; Treatment Outcome ; Wound Healing/physiology ; Wound Infection/*etiology/physiopathology/therapy ; }, abstract = {Moisture-associated skin damage (MASD) occurs when excessive moisture in urine, stool, and wound exudate leads to inflammation of the skin, with or without erosion or secondary cutaneous infection. This article, produced by a panel of clinical experts who met to discuss moisture as an etiologic factor in skin damage, focuses on peristomal moisture-associated dermatitis and periwound moisture-associated dermatitis. The principles outlined here address assessment, prevention, and treatment of MASD affecting the peristomal or periwound skin.}, }
@article {pmid21871249, year = {2011}, author = {Bakken, JS and Borody, T and Brandt, LJ and Brill, JV and Demarco, DC and Franzos, MA and Kelly, C and Khoruts, A and Louie, T and Martinelli, LP and Moore, TA and Russell, G and Surawicz, C and , }, title = {Treating Clostridium difficile infection with fecal microbiota transplantation.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {9}, number = {12}, pages = {1044-1049}, pmid = {21871249}, issn = {1542-7714}, support = {R21 AI091907/AI/NIAID NIH HHS/United States ; R21 AI091907-01/AI/NIAID NIH HHS/United States ; R21 AI091907-02/AI/NIAID NIH HHS/United States ; 1R21AI091907/AI/NIAID NIH HHS/United States ; }, mesh = {Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*therapy ; Feces/*microbiology ; Humans ; Probiotics/*administration &amp; dosage ; Treatment Outcome ; }, abstract = {Clostridium difficile infection is increasing in incidence, severity, and mortality. Treatment options are limited and appear to be losing efficacy. Recurrent disease is especially challenging; extended treatment with oral vancomycin is becoming increasingly common but is expensive. Fecal microbiota transplantation is safe, inexpensive, and effective; according to case and small series reports, about 90% of patients are cured. We discuss the rationale, methods, and use of fecal microbiota transplantation.}, }
@article {pmid21857820, year = {2011}, author = {Frederick, RT}, title = {Current concepts in the pathophysiology and management of hepatic encephalopathy.}, journal = {Gastroenterology &amp; hepatology}, volume = {7}, number = {4}, pages = {222-233}, pmid = {21857820}, issn = {1554-7914}, abstract = {Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or portosystemic shunting of blood flow. The pathophysiology of this disease is quite complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Recent hypotheses implicate low-grade cerebral edema as a final common pathway for the pathophysiology of HE. Management of this condition is multifaceted and requires several steps: elimination of precipitating factors; removal of toxins, both by reducing them at their source and by augmenting scavenging pathways; modulation of resident fecal flora; proper nutritional support; and downregulation of systemic and gut-derived inflammation.}, }
@article {pmid21844802, year = {2011}, author = {Didier, ES and Weiss, LM}, title = {Microsporidiosis: not just in AIDS patients.}, journal = {Current opinion in infectious diseases}, volume = {24}, number = {5}, pages = {490-495}, pmid = {21844802}, issn = {1473-6527}, support = {AI071778/AI/NIAID NIH HHS/United States ; R01 AI031788-20/AI/NIAID NIH HHS/United States ; P51 RR000164/RR/NCRR NIH HHS/United States ; R21 AI093315-01/AI/NIAID NIH HHS/United States ; RR00164/RR/NCRR NIH HHS/United States ; R01 AI031788/AI/NIAID NIH HHS/United States ; R01 AI071778/AI/NIAID NIH HHS/United States ; R21 AI093315/AI/NIAID NIH HHS/United States ; }, mesh = {AIDS-Related Opportunistic Infections/*microbiology ; Antiprotozoal Agents/therapeutic use ; Humans ; Immunocompromised Host ; Microsporidiosis/diagnosis/*epidemiology/therapy ; }, abstract = {PURPOSE OF REVIEW: Microsporidia have emerged as causes of opportunistic infections associated with diarrhea and wasting in AIDS patients. This review describes recent reports of microsporidiosis in HIV-infected individuals and the growing awareness of microsporidiosis in non-HIV-infected populations.<br><br>RECENT FINDINGS: Microsporidia were only rarely recognized as causes of disease in humans until the AIDS pandemic. Implementation of combination antiretroviral therapy (cART) to curtail HIV replication and restore immune status drastically reduced the occurrence of opportunistic infections, including those due to microsporidia, in HIV-infected individuals. In developing countries where cART is not always accessible, microsporidiosis continues to be problematic. Improvement of diagnostic methods over the previous 25 years led to identification of several new species of microsporidia, many of which disseminate from enteric to systemic sites of infection and contribute to some unexpected lesions. Among non-HIV-infected but immune-suppressed individuals, microsporidia have infected organ transplant recipients, children, the elderly, and patients with malignant disease and diabetes. In otherwise healthy immune-competent HIV seronegative populations, self-limiting diarrhea occurred in travelers and as a result of a foodborne outbreak associated with contaminated cucumbers. Keratitis due to microsporidiosis has become problematic and a recent longitudinal evaluation demonstrated that non-HIV-infected individuals seropositive for microsporidia who had no clinical signs continued to intermittently shed organisms in feces and urine.<br><br>SUMMARY: Greater awareness and implementation of better diagnostic methods are demonstrating that microsporidia contribute to a wide range of clinical syndromes in HIV-infected and non-HIV-infected people. As such, microsporidia should be considered in differential diagnoses if no other cause can be defined.}, }
@article {pmid21839773, year = {2011}, author = {Siddiq, DM and Koo, HL and Adachi, JA and Viola, GM}, title = {Norovirus gastroenteritis successfully treated with nitazoxanide.}, journal = {The Journal of infection}, volume = {63}, number = {5}, pages = {394-397}, pmid = {21839773}, issn = {1532-2742}, support = {K23 DK084513/DK/NIDDK NIH HHS/United States ; R01 DK084512/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Anti-Infective Agents/*therapeutic use ; Caliciviridae Infections/*drug therapy/virology ; Diagnosis, Differential ; Feces/virology ; Gastroenteritis/*drug therapy/virology ; Graft vs Host Disease/complications ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Immunosuppression Therapy ; Leukemia, Myeloid, Acute/*complications/therapy ; Male ; Nitro Compounds ; Norovirus/drug effects/genetics/*isolation &amp; purification ; Reverse Transcriptase Polymerase Chain Reaction ; Thiazoles/*therapeutic use ; }, abstract = {Infectious diarrhea is a common occurrence in the immunosuppressed population. We present a 43-year-old individual with large-volume stool output Norovirus acute gastroenteritis in the setting of relapsed refractory acute myelogenous leukemia, hematopoietic stem cell transplantation, and biopsy-proven cutaneous and pulmonary graft-versus-host disease. Therapeutic options such as intravenous immunoglobulin or reduction of immunosuppressants were not a feasible choice. A prompt clinical cure was achieved with nitazoxanide, a broad-spectrum antimicrobial agent. Nitazoxanide may be a safe therapeutic alternative, in which a reduction in immunosuppression may not be a viable option.}, }
@article {pmid21801071, year = {2011}, author = {Nishida, H and Nakayama, M and Tanaka, H and Kitamura, M and Hatoya, S and Sugiura, K and Suzuki, Y and Ide, C and Inaba, T}, title = {Evaluation of transplantation of autologous bone marrow stromal cells into the cerebrospinal fluid for treatment of chronic spinal cord injury in dogs.}, journal = {American journal of veterinary research}, volume = {72}, number = {8}, pages = {1118-1123}, doi = {10.2460/ajvr.72.8.1118}, pmid = {21801071}, issn = {1943-5681}, mesh = {Animals ; Bone Marrow Transplantation/methods/*veterinary ; Cerebrospinal Fluid/*cytology/physiology ; Dogs ; Female ; Locomotion ; Male ; Recovery of Function ; Spinal Cord/cytology/pathology/*transplantation ; Spinal Cord Injuries/pathology/physiopathology/therapy/*veterinary ; Stromal Cells/*transplantation ; Transplantation, Autologous/methods/veterinary ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate effects of transplantation of bone marrow stromal cells (BMSCs) into the CSF for the treatment of chronic spinal cord injury in dogs that had not responded by 1 month after decompressive surgery.<br><br>ANIMALS: 23 dogs.<br><br>PROCEDURES: Dogs with paraplegia and loss of nociception in the pelvic limbs for at least 1 month after decompressive surgery were assigned to transplantation or control groups. Dogs in the transplantation group received BMSCs injected into the CSF 1 to 3 months after decompressive surgery. Dogs in the control group did not receive additional treatments. Improvements in gait, proprioceptive positioning, and nociception were evaluated by use of the Texas Spinal Cord Injury Scale for &#x2265; 6 months after BMSC transplantation.<br><br>RESULTS: 6 of 10 dogs in the transplantation group regained the ability to walk, whereas only 2 of 13 dogs in the control group regained the ability to walk. Scores for the Texas Spinal Cord Injury Scale in the transplantation group were significantly higher than scores in the control group at the endpoint of the study (6 months after BMSC transplantation or after decompressive surgery for the transplantation and control groups, respectively). Only 1 dog (transplantation group) recovered nociception. All dogs from both groups had fecal and urinary incontinence. No complications were observed in relation to BMSC transplantation.<br><br>Injection of BMSCs into the CSF caused no complications and could have beneficial effects on pelvic limb locomotion in dogs with chronic spinal cord injuries.}, }
@article {pmid21792556, year = {2012}, author = {Ohkubo, T and Sugawara, Y and Takayama, T and Kokudo, N and Makuuchi, M}, title = {The risk factors of fungal infection in living-donor liver transplantations.}, journal = {Journal of hepato-biliary-pancreatic sciences}, volume = {19}, number = {4}, pages = {382-388}, doi = {10.1007/s00534-011-0423-4}, pmid = {21792556}, issn = {1868-6982}, mesh = {Adolescent ; Adult ; Aspergillosis/epidemiology ; Biliary Atresia/surgery ; Candidiasis/epidemiology ; Child ; Child, Preschool ; Cholangitis, Sclerosing/surgery ; Female ; Humans ; Infant ; Kaplan-Meier Estimate ; Liver Cirrhosis/surgery ; Liver Transplantation/*adverse effects/*mortality ; Living Donors ; Male ; Middle Aged ; Multivariate Analysis ; Mycoses/*epidemiology/mortality ; Pneumocystis Infections/epidemiology ; Pneumocystis carinii ; Retrospective Studies ; Risk Factors ; Young Adult ; }, abstract = {PURPOSE: The aim of the study was to retrospectively assess in a Japanese university hospital the risk factors for fungal infections and mortality in living-donor liver transplantations (LDLTs). Although fungal infections are an important complication associated with high mortality in liver transplantation, the risk factors for fungal infections developing after LDLT remain poorly understood.<br><br>METHODS: Patient records for a total of 156 patients undergoing LDLT over a 6-year period in our institution were retrospectively evaluated. All transplant recipients were routinely observed for fungal infections with close monitoring for febrile episodes and collection and culture of saliva, pharynx, sputum, urine, feces, and drain discharge specimens undertaken. Fungal infection was defined as proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group. Patients with definite or probable infection were diagnosed as having specific invasive fungal infection in this study. Data were reviewed and collated from these patients' records, and multivariate analyses were performed to identify possible risk factors for mortality and the development of fungal infections.<br><br>RESULTS: Nineteen of 156 patients (12.2%) developed invasive fungal infections, involving Candida spp. (n = 13), Pneumocystis jiroveci (n = 4), and Aspergillus spp. (n = 2). Eight of these 19 patients died, 4 from pneumonia, and 1 each from cerebral hemorrhage, chronic rejection, virus-associated hemophagocytic syndrome, and cancer recurrence. The 5-year survival rate was significantly lower in patients with fungal infections than in those without (53 vs. 90%; p < 0.001). Fungal infection was independently associated with reoperation (odds ratio 6.92, 1.82-26.27, p = 0.004), posttransplant dialysis (5.62, 1.51-20.88, p = 0.009), and bacterial infection (3.94, 1.02-15.26, p = 0.04).<br><br>CONCLUSION: Independent risk factors of fungal infection after LDLT are reoperation, posttransplant dialysis, and bacterial infection.}, }
@article {pmid21773665, year = {2011}, author = {Toso M, A and Vial U, F and Galanti, N}, title = {[Oral transmission of Chagas' disease].}, journal = {Revista medica de Chile}, volume = {139}, number = {2}, pages = {258-266}, pmid = {21773665}, issn = {0717-6163}, mesh = {Animals ; Chagas Disease/*transmission ; *Food Contamination ; Food Parasitology ; Humans ; Latin America ; Trypanosoma cruzi/parasitology ; }, abstract = {The traditional transmission pathways of Chagas' disease are vectorial, transfusional, transplacental and organ transplantation. However, oral transmission is gaining importance. The first evidence of oral transmission was reported in Brazil in 1965. Nowadays the oral route is the transmission mode in 50% of cases in the Amazon river zone. Oral infection is produced by the ingestion of infected triatomine bugs or their feces, undercooked meat from infested host animals and food contaminated with urine or anal secretion of infected marsupials. Therefore travelers to those zones should be advised about care to be taken with ingested food. In Chile, this new mode of transmission should be considered in public health policies.}, }
@article {pmid21744097, year = {2011}, author = {Abbas, MA}, title = {Wide local excision for Buschke-Löwenstein tumor or circumferential carcinoma in situ.}, journal = {Techniques in coloproctology}, volume = {15}, number = {3}, pages = {313-318}, pmid = {21744097}, issn = {1128-045X}, mesh = {Adolescent ; Adult ; Aged ; Anus Neoplasms/complications/pathology/*surgery ; Carcinoma in Situ/complications/pathology/*surgery ; Child ; Child, Preschool ; Condylomata Acuminata/complications/pathology/*surgery ; Fecal Incontinence/*etiology ; Female ; HIV Seropositivity/complications ; Humans ; Length of Stay ; Male ; Middle Aged ; Postoperative Complications/*etiology ; Recurrence ; Retrospective Studies ; Skin Transplantation ; Surgical Flaps ; Young Adult ; }, abstract = {PURPOSE: This study aimed to evaluate the outcome of patients with Buschke-Löwenstein tumor or circumferential anal carcinoma in situ who underwent wide local excision with flap or skin graft coverage of the wound.<br><br>METHODS: A retrospective review was conducted of all patients operated at Kaiser Permanente Los Angeles Medical Center during a 6-year period. Outcome measures included postoperative complications, functional results, recurrence rate, and re-intervention rate.<br><br>RESULTS: Of 152 patients operated for dysplastic anal lesions or tumors, 10 (7%) underwent wide local excision for Buschke-L&#xf6;wenstein tumor or circumferential anal carcinoma in situ [men 70%, mean age 36 years]. Median duration of symptoms was 5 years. Eighty percent of patients had prior operations and 50% were positive for the human immunodeficiency virus. Mean size of the lesion was 41 cm(2). Microscopic margin positivity was noted in 60%. Wound was closed with house advancement flap in majority of patients. Only one patient had fecal diversion. Median length of stay was 2 days. Postoperative complications were noted in 50% of patients. Rate of transient postoperative incontinence was 30%. Recurrent disease was noted in 3 patients with the human immunodeficiency virus [median follow-up: 18 months]. All recurrences were treated with local fulguration or medication.<br><br>CONCLUSION: Wide local excision with flap or skin graft coverage is an option for patients with Buschke-L&#xf6;wenstein tumor or circumferential anal carcinoma in situ. Close postoperative surveillance is advised due to the risk of recurrent disease, especially in patients with the human immunodeficiency virus.}, }
@article {pmid21716124, year = {2011}, author = {Brandt, LJ and Borody, TJ and Campbell, J}, title = {Endoscopic fecal microbiota transplantation: "first-line" treatment for severe clostridium difficile infection?.}, journal = {Journal of clinical gastroenterology}, volume = {45}, number = {8}, pages = {655-657}, doi = {10.1097/MCG.0b013e3182257d4f}, pmid = {21716124}, issn = {1539-2031}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/*pathogenicity ; Colectomy ; *Colonoscopy ; Drug Resistance, Bacterial ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*therapy ; Feces/*microbiology ; Humans ; *Metagenome ; Patient Selection ; Recurrence ; Severity of Illness Index ; Treatment Outcome ; }, }
@article {pmid21705122, year = {2011}, author = {Hoppe, B and Dittlich, K and Fehrenbach, H and Plum, G and Beck, BB}, title = {Reduction of plasma oxalate levels by oral application of Oxalobacter formigenes in 2 patients with infantile oxalosis.}, journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation}, volume = {58}, number = {3}, pages = {453-455}, doi = {10.1053/j.ajkd.2011.05.012}, pmid = {21705122}, issn = {1523-6838}, mesh = {Administration, Oral ; Feces/microbiology ; Female ; Humans ; Hyperoxaluria/*blood/complications/genetics/*therapy ; Hyperoxaluria, Primary ; Infant ; Kidney Transplantation ; Mutation, Missense ; Nephrocalcinosis/etiology ; Oxalates/*blood ; *Oxalobacter formigenes/isolation &amp; purification ; Renal Insufficiency ; Transaminases/blood/deficiency/genetics ; }, abstract = {The spectrum of primary hyperoxaluria type I is extremely heterogeneous, ranging from singular to recurrent urolithiasis and early end-stage renal disease (ESRD). In infantile oxalosis, the most devastating form, ESRD occurs as early as within the first weeks of life. No kidney replacement therapy sufficiently removes endogenously overproduced oxalate. However, curative combined liver-kidney transplant often is impracticable in small infants. Oxalobacter formigenes (O formigenes), an anaerobic oxalate-degrading bacterium, is a colonizer of the healthy human colon. Oral administration of O formigenes has been shown to significantly decrease urine and plasma oxalate levels in patients with primary hyperoxaluria. We report compassionate use of O formigenes in two 11-month-old girls with infantile oxalosis and ESRD. They received O formigenes twice a day for 4 weeks (or until transplant). Dialysis regimens were unchanged. Plasma oxalate levels decreased from >110 μmol/L before to 71.53 μmol/L under treatment in patient 1 and from >90 to 68.56 μmol/L (first treatment period) and 50.05 μmol/L (second treatment period) in patient 2. O formigenes was well tolerated. No serious side effects were reported. Extremely increased plasma oxalate levels in patients with infantile oxalosis may enable intestinal elimination of endogenous oxalate in the presence of O formigenes. Therefore, O formigenes therapy may be helpful as a bridging procedure until transplant in such patients.}, }
@article {pmid21682755, year = {2011}, author = {Landy, J and Al-Hassi, HO and McLaughlin, SD and Walker, AW and Ciclitira, PJ and Nicholls, RJ and Clark, SK and Hart, AL}, title = {Review article: faecal transplantation therapy for gastrointestinal disease.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {34}, number = {4}, pages = {409-415}, doi = {10.1111/j.1365-2036.2011.04737.x}, pmid = {21682755}, issn = {1365-2036}, mesh = {Bacterial Physiological Phenomena ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Gastrointestinal Tract/*microbiology ; Humans ; *Microbial Interactions ; }, abstract = {BACKGROUND: Evidence is emerging regarding the relationship between a dysbiosis of the human gut microbiota and a number of gastrointestinal diseases as well as diseases beyond the gut. Probiotics have been investigated in many gastrointestinal disease states, with variable and often modest outcomes. Faecal transplantation is an alternative approach to manipulate the gut microbiota.<br><br>AIM: To review the use of faecal transplantation therapy for the management of gastrointestinal disorders.<br><br>METHODS: Available articles on faecal transplantation in the management of gastrointestinal disorders were identified using a Pubmed search and bibliographies of review articles on the subject were collated.<br><br>RESULTS: A total of 239 patients who had undergone faecal transplantation were reported. Seventeen of 22 studies of faecal transplantation were in fulminant or refractory Clostridium difficile. Studies of faecal transplantation are heterogeneous regarding the patients, donors, screening, methods of administration and definition of response. Faecal transplantation for C. difficile has been demonstrated to be effective in 145/166 (87%) patients. Small numbers of patients are reported to have undergone successful faecal transplantation for irritable bowel syndrome and inflammatory bowel disease.<br><br>CONCLUSIONS: Faecal transplantation has been reported with good outcomes for fulminant and refractory C. difficile. No adverse effects of faecal transplantation have been reported. However, there are no level 1 data of faecal transplantation and reports to date may suffer from reporting bias of positive outcomes and under-reporting of adverse effects. This therapy holds great promise, where a dysbiosis of the gut microbiota is responsible for disease and further studies are necessary to explore this potential.}, }
@article {pmid21658638, year = {2011}, author = {Colombo, C and Ellemunter, H and Houwen, R and Munck, A and Taylor, C and Wilschanski, M and , }, title = {Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients.}, journal = {Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society}, volume = {10 Suppl 2}, number = {}, pages = {S24-8}, doi = {10.1016/S1569-1993(11)60005-2}, pmid = {21658638}, issn = {1873-5010}, mesh = {Colon ; *Constipation/diagnosis/epidemiology/therapy ; Cystic Fibrosis/*epidemiology ; Humans ; Ileum ; *Intestinal Obstruction/diagnosis/epidemiology/therapy ; Medicine/*standards ; *Practice Guidelines as Topic ; Risk Factors ; }, abstract = {Complete or incomplete intestinal obstruction by viscid faecal material in the terminal ileum and proximal colon - distal intestinal obstruction syndrome (DIOS) - is a common complication in cystic fibrosis. Estimates of prevalence range from 5 to 12 episodes per 1000 patients per year in children, with higher rates reported in adults. DIOS is mainly seen in patients with pancreatic insufficiency, positive history of meconium ileus and previous episodes of DIOS. DIOS is being described with increasing frequency following organ transplantation. Diagnosis is based on suggestive symptoms with a right lower quadrant mass confirmed on X-ray. The main differential is chronic constipation. Treatment consists of rehydration combined with stool softening laxatives or gut lavage with balanced electrolyte solutions. Rapid fluid shifts have been described following osmotic agents. Avoiding dehydration and optimizing pancreatic enzyme dosage may reduce the chance of further episodes. Prophylactic laxative therapy is widely used, but is not evidence-based.}, }
@article {pmid21676279, year = {2011}, author = {Shintoku, Y and Takagi, H and Kadosaka, T and Nagaoka, F and Kondo, S and Itoh, M and Honda, S and Kimura, E}, title = {Strongyloides ratti: transplantation of adults recovered from the small intestine at different days after infection into the colon of naive and infection-primed Wistar rats, and the effect of antioxidant treatment on large intestinal parasitism.}, journal = {Parasitology}, volume = {138}, number = {8}, pages = {1053-1060}, doi = {10.1017/S0031182011000631}, pmid = {21676279}, issn = {1469-8161}, mesh = {Animals ; Antioxidants/*pharmacology ; Body Size ; Butylated Hydroxyanisole/*pharmacology ; Colon/*parasitology ; Feces/parasitology ; Host-Parasite Interactions ; Intestine, Small/*parasitology ; Male ; Parasite Egg Count ; Rats ; Rats, Wistar ; Strongyloides ratti/drug effects/*pathogenicity ; Strongyloidiasis/*parasitology ; Time Factors ; }, abstract = {Strongyloides ratti (Nagoya strain) is unique in that a portion of adults parasitizing the small intestine withstands 'worm expulsion', which starts at around day 8 post-infection (p.i.) by host immunity, and establishes in the large intestine after day 19 p.i. To investigate the mechanism, adults obtained from the small intestine at day 7 or 19 p.i. were transplanted into the colon of infection-primed immune rats. Adults obtained at day 7 p.i. were rejected quickly, whereas those obtained at day 19 p.i. could establish infection. Moreover, the body length and the number of intrauterine eggs increased in the large intestine. In a separate experiment, large intestinal parasitism was abolished by the treatment of host rats with an anti-oxidant, butylated hydroxyanisole. These results indicate that small intestinal adults between days 7 and 19 p.i. acquired the ability to parasitize the large intestine of immune rats, and that free radicals produced by the host may have played a significant role in the process.}, }
@article {pmid21654242, year = {2011}, author = {Wong, MT and Meurette, G and Stangherlin, P and Lehur, PA}, title = {The magnetic anal sphincter versus the artificial bowel sphincter: a comparison of 2 treatments for fecal incontinence.}, journal = {Diseases of the colon and rectum}, volume = {54}, number = {7}, pages = {773-779}, doi = {10.1007/DCR.0b013e3182182689}, pmid = {21654242}, issn = {1530-0358}, mesh = {Adult ; Aged ; Anal Canal/*surgery ; Defecation ; Feasibility Studies ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Intestines/*transplantation ; Magnetics/*instrumentation ; Middle Aged ; Patient Satisfaction ; Prosthesis Design ; Prosthesis Implantation/*methods ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal incontinence is a debilitating ailment, and surgery offers the only recourse for the patients in whom conservative treatment fails.<br><br>OBJECTIVE: This study aims to report the first matched comparison between patients implanted with the magnetic anal sphincter and the artificial bowel sphincter.<br><br>PATIENTS AND INTERVENTIONS: From December 2008 to June 2010, 10 female patients, median age 64.5 years (range, 42-76), with severe fecal incontinence for a median of 7.5 years (range, 1-40), were implanted with the magnetic anal sphincter. Ten female patients implanted with the artificial bowel sphincter were identified. Both groups were matched for age, etiology, duration of incontinence, and preoperative functional scores.<br><br>MAIN OUTCOME MEASURES: Outcomes measures included length of hospitalization, complications, and changes in functional scores (anorectal physiology, incontinence, and quality of life).<br><br>RESULTS: Patients with the magnetic anal sphincter had a shorter median operative time (62 vs 97.5 min, P = .0273), length of hospitalization(4.5 vs 10 days, P < .001), and follow-up duration (8 vs 22.5 mo, P = .0068), without a statistically significant difference in 30-day complications (4 vs 2, P = .628) and revision/explantation (1 vs 4, P = .830). Both groups achieved significant improvements in preoperative incontinence (P < .0002) and quality-of-life scores (P < .009). In a comparison of baseline resting anal pressures, patients with the artificial bowel sphincter had significantly higher pressures with the cuff inflated (P = .0082), and those with the magnetic anal sphincter had a significant increase as well (P = .0469). At the latest review, both groups had similar quality-of-life scores (P = .374); patients with the artificial bowel sphincter had higher (median) closed-cuff anal pressures compared with the anal resting pressure of those with a magnetic anal sphincter (89 vs 58.5 cmH2O, P = .0147), together with more constipation (4 vs 1, P = .830) and a trend toward better incontinence scores (P = .0625).<br><br>LIMITATIONS: This was a nonrandomized study with small patient numbers.<br><br>CONCLUSION: In the short term, the magnetic anal sphincter is as effective as the artificial bowel sphincter in restoring continence and quality of life.}, }
@article {pmid21645246, year = {2011}, author = {Pruett, T}, title = {Feces in our food, viruses in our organs: donor surveillance, organ transplantation and the risk for disease transmission.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {11}, number = {6}, pages = {1115-1116}, doi = {10.1111/j.1600-6143.2011.03600.x}, pmid = {21645246}, issn = {1600-6143}, mesh = {*Disease Transmission, Infectious ; *Feces ; *Food Contamination ; Humans ; *Tissue Donors ; Viruses/*isolation &amp; purification ; }, }
@article {pmid21644089, year = {2011}, author = {Kement, M and Acar, HA and Barlas, IS and Aksakal, N and Gezen, C and Düzci, U and Oncel, M}, title = {Clinical evaluation of a temporary fecal containment device for non-surgical fecal diversion in perineal burns.}, journal = {Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma &amp; emergency surgery : TJTES}, volume = {17}, number = {2}, pages = {123-127}, doi = {10.5505/tjtes.2011.66563}, pmid = {21644089}, issn = {1306-696X}, mesh = {Adult ; Aged ; Body Surface Area ; Burns/complications/pathology/*therapy ; Burns, Electric/complications/therapy ; Catheterization/instrumentation ; Fecal Incontinence/etiology/*therapy ; Female ; Humans ; Length of Stay ; Male ; Middle Aged ; Perineum/*injuries ; Retrospective Studies ; Risk Factors ; Safety ; Skin Diseases, Infectious/prevention &amp; control ; Skin Transplantation/standards ; Time Factors ; Transplantation, Autologous ; Young Adult ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the clinical results of a temporary fecal containment device (Flexi-Seal® FMS) in our burn center.<br><br>METHODS: All patients in whom temporary fecal containment devices were applied for perineal burns between August 2008 and August 2009 in our institution were reviewed. Demographics, etiology of burns, total body surface area (TBSA) burned, intensive care unit (ICU) need, early mortality, and post-application data were obtained from a prospectively designed database. In addition, some variables were investigated as potential risks factors for fecal leakage.<br><br>RESULTS: The mean age of patients (n=15) was 43.1&#xb1;22.1 years, and 66.7% of the patients were male. The mean %TBSA burned was 40.7&#xb1;16.6. Fecal leakage was seen in 6 patients. Local infection in the perineum was observed in 6 patients, including 4 of the 6 patients with fecal leakage. The mortality rate was 33% (5 deaths). All exitus patients had 50% or more TBSA burned. Electrical burn injury was found as a significant risk factor for fecal leakage in surviving patients (p<0.05). Autologous split-thickness grafting was performed in 8 patients without complication. The mean duration of catheterization was 22.5&#xb1;5.7 days. Except for superficial mucosal erosion in the distal rectum in 2 cases, no complication was observed. The mean hospitalization time was 46.7&#xb1;12.7 days.<br><br>CONCLUSION: If the safety of these devices is proven in further prospective, high-volume studies, they may reduce the necessity of diverting stoma operation in burn patients.}, }
@article {pmid21633181, year = {2011}, author = {Tilg, H and Kaser, A}, title = {Gut microbiome, obesity, and metabolic dysfunction.}, journal = {The Journal of clinical investigation}, volume = {121}, number = {6}, pages = {2126-2132}, pmid = {21633181}, issn = {1558-8238}, support = {260961/ERC_/European Research Council/International ; }, mesh = {Animals ; Bacteria/drug effects/metabolism ; Bacterial Translocation ; Dietary Carbohydrates/pharmacokinetics/pharmacology ; Dietary Fats/pharmacokinetics/pharmacology ; Digestion ; Disease Models, Animal ; Energy Metabolism ; Gastrointestinal Tract/*microbiology ; Genetic Predisposition to Disease ; Germ-Free Life ; Humans ; Inflammation ; Metabolic Diseases/etiology/immunology/*microbiology/physiopathology ; Metabolic Networks and Pathways ; Metagenome/drug effects/*physiology ; Mice ; Mice, Mutant Strains ; Obesity/etiology/genetics/immunology/*microbiology/physiopathology ; Species Specificity ; }, abstract = {The prevalence of obesity and related disorders such as metabolic syndrome has vastly increased throughout the world. Recent insights have generated an entirely new perspective suggesting that our microbiota might be involved in the development of these disorders. Studies have demonstrated that obesity and metabolic syndrome may be associated with profound microbiotal changes, and the induction of a metabolic syndrome phenotype through fecal transplants corroborates the important role of the microbiota in this disease. Dietary composition and caloric intake appear to swiftly regulate intestinal microbial composition and function. As most findings in this field of research are based on mouse studies, the relevance to human biology requires further investigation.}, }
@article {pmid21602110, year = {2011}, author = {Wang, CH and Lee, SC and Huang, SS and Chang, LC}, title = {Hookworm infection in a healthy adult that manifested as severe eosinphilia and diarrhea.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {44}, number = {6}, pages = {484-487}, doi = {10.1016/j.jmii.2011.04.010}, pmid = {21602110}, issn = {1995-9133}, mesh = {Ancylostoma/isolation &amp; purification ; Ancylostomiasis/*diagnosis/drug therapy/parasitology ; Animals ; Antinematodal Agents/therapeutic use ; Colon/parasitology ; Diarrhea/*parasitology ; Eosinophilia/*parasitology ; Feces/parasitology ; Humans ; Male ; Mebendazole/therapeutic use ; Middle Aged ; Sigmoidoscopy ; }, abstract = {A 54-year-old male was admitted because of having suffered from progressive watery diarrhea for 12 days. He had no history of diabetes mellitus, hypertension, heart disease, organ transplantation, or malignancy. After admission, he still complained of diarrhea despite medical treatment. The laboratory examination showed leukocytosis with eosinophilia and a stool examination by the concentration method was negative four times. When a sigmoidoscopy was performed as a part of an explorative survey, a single protruding mass consisting if a moving adult hookworm was found. The fifth stool examination by the concentration method identified hookworm ova. The patient was treated with oral mebendazole 100 mg twice a day for 3 days. The diarrhea and eosinophilia subsided after this treatment.}, }
@article {pmid21592502, year = {2011}, author = {Barron, MA and Makhija, M and Hagen, LE and Pencharz, P and Grunebaum, E and Roifman, CM}, title = {Increased resting energy expenditure is associated with failure to thrive in infants with severe combined immunodeficiency.}, journal = {The Journal of pediatrics}, volume = {159}, number = {4}, pages = {628-32.e1}, doi = {10.1016/j.jpeds.2011.03.041}, pmid = {21592502}, issn = {1097-6833}, mesh = {Calorimetry, Indirect ; Diarrhea/epidemiology ; Energy Metabolism/*physiology ; Failure to Thrive/*physiopathology/therapy ; Feces/virology ; Humans ; Infant ; Infant Formula ; Infant, Newborn ; Infections/epidemiology ; Intubation, Gastrointestinal ; Logistic Models ; Mutation ; Parenteral Nutrition ; Pneumonia/epidemiology ; Receptors, Interleukin-2/genetics ; Rest/*physiology ; Retrospective Studies ; Severe Combined Immunodeficiency/*physiopathology ; }, abstract = {OBJECTIVES: To measure resting energy expenditure (REE) and determine whether increased REE (hypermetabolism) is associated with failure to thrive (FTT) in patients with severe combined immunodeficiency (SCID) at diagnosis.<br><br>STUDY DESIGN: REE was measured in 26 patients with SCID in a single transplant center. Predicted REE was determined with World Health Organization standards. Measured REE >110% of predicted REE was classified as hypermetabolism. Other data collected included FTT status, infections, genotype, phenotype, and the feeding methods used.<br><br>RESULTS: Fifteen of 26 patients (57.7%) had FTT, and 18 of 26 patients (69.2%) were hypermetabolic. Hypermetabolism occured in 14 of 15 patients (93%) with FTT, and only 4 of 11 patients (36%) without FTT had hypermetabolism (P = .003). There was a significant difference between the measured REE (71.75 &#xb1; 16.6 kcal/kg) and the predicted REE (52.85 &#xb1; 2.8 kcal/kg; P < .0001). Eleven of 17 patients (65%) required nasogastric feeding, parenteral nutrition, or both to meet their energy needs.<br><br>CONCLUSIONS: Hypermetabolism is common in patients with SCID and may contribute to the development of FTT. The hypermetabolism in these patients may necessitate intensive nutrition support.}, }
@article {pmid21568363, year = {2011}, author = {van Nispen tot Pannerden, CM and Verbon, A and Kuipers, EJ}, title = {Recurrent Clostridium difficile infection: what are the treatment options?.}, journal = {Drugs}, volume = {71}, number = {7}, pages = {853-868}, pmid = {21568363}, issn = {1179-1950}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Clostridioides difficile/*drug effects ; Clostridium Infections/*drug therapy/microbiology ; Humans ; }, abstract = {Clostridium difficile infection (CDI) is an increasing problem in hospitalized patients. Recurrences of disease, despite the recommended treatments with metronidazole or vancomycin, are frequently seen and pose major problems for the clinical management of patients with CDI. Evidence for efficient clinical cure and low recurrence rates with primary use of alternative antibacterial treatment, such as fidaxomicin and rifaximin, is growing and these treatment strategies need further exploration. The use of probiotics (e.g. Saccharomyces boulardii) may be considered, as well as combination therapy with vancomycin. Other promising therapies are the use of (monoclonal) antibodies and faecal transplantation, the efficacy of which has been suggested in smaller studies. Large studies evaluating faecal transplantation and other microbial products are underway. This article focuses on recurrent CDI and the possibilities for treatment and reduction of recurrence rates. Furthermore, general concepts of CDI and the primary treatment strategies are discussed. In summary, recurrent CDI remains a challenging clinical entity for which more treatment options will be forthcoming in the next few years.}, }
@article {pmid21555954, year = {2011}, author = {Martin, L}, title = {Modified fecal transplantation.}, journal = {Journal of clinical gastroenterology}, volume = {45}, number = {8}, pages = {742}, doi = {10.1097/MCG.0b013e3182166c8b}, pmid = {21555954}, issn = {1539-2031}, mesh = {Clostridioides difficile/*pathogenicity ; Clostridium Infections/*drug therapy/microbiology ; Feces/*microbiology ; Gastroenteritis/microbiology/*therapy ; Humans ; Intestines/*microbiology ; }, }
@article {pmid21555950, year = {2011}, author = {Ho, N and Prasad, V}, title = {Clostridium difficile diarrhea and fecal transplantation.}, journal = {Journal of clinical gastroenterology}, volume = {45}, number = {8}, pages = {742-743}, doi = {10.1097/MCG.0b013e31821b1094}, pmid = {21555950}, issn = {1539-2031}, mesh = {Clostridioides difficile/*pathogenicity ; Clostridium Infections/*drug therapy ; Feces/*microbiology ; Gastroenteritis/*therapy ; Humans ; Intestines/*microbiology ; }, }
@article {pmid21546726, year = {2011}, author = {Husain, M and Khan, RN and Rehmani, B and Haris, H}, title = {Omental patch technique for the ileal perforation secondary to typhoid fever.}, journal = {Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association}, volume = {17}, number = {3}, pages = {208-211}, pmid = {21546726}, issn = {1998-4049}, mesh = {Adolescent ; Adult ; Child ; Female ; Humans ; Ileal Diseases/*etiology/*surgery ; Intestinal Perforation/*etiology/*surgery ; Laparotomy/methods ; Male ; Omentum/*transplantation ; Peritonitis/etiology/*surgery ; Typhoid Fever/*complications ; Young Adult ; }, abstract = {BACKGROUND/AIM: Enteric perforation is a grave complication of typhoid fever. Laparotomy with primary closure is the treatment of choice depending upon the bowel condition. Fecal fistula formation is the main concern in primary closure and the incidence of this complication dramatically decreases when omentum is used as a patch over primary closure.<br><br>MATERIALS AND METHODS: A total of 176 patients underwent laparotomy for enteric perforation and they were divided into two groups randomly; Group I--Primary closure with omental patch and Group II--Only primary closure. The outcomes were measured in relation to hospital stay, wound infection, septicemia, fecal fistula, and mortality.<br><br>RESULTS: The incidence of complications including fecal fistula and mortality is significantly lower in the group I patients. Fecal fistula occurs in 7.7% in group II, while in only 1.1% in group I. The mortality is also lower 3.3% in group II, while 1.1% in group I.<br><br>CONCLUSION: Primary closure with omental patch is a better option as compared with only primary closure in enteric perforation patients. It can be recommended as an alternative method to primary closure only in enteric perforation patients.}, }
@article {pmid21545998, year = {2011}, author = {Goldsmith, HS and Chandra, A}, title = {Pyloric valve transposition as substitute for a colostomy in humans: a preliminary report.}, journal = {American journal of surgery}, volume = {202}, number = {4}, pages = {409-416}, doi = {10.1016/j.amjsurg.2010.11.012}, pmid = {21545998}, issn = {1879-1883}, mesh = {Adolescent ; Adult ; Anal Canal/abnormalities/*injuries/surgery ; Child ; Fecal Incontinence/etiology/*surgery ; Female ; Humans ; Male ; Omentum/blood supply ; Pylorus/*blood supply/*transplantation ; Wounds and Injuries/complications/*surgery ; Young Adult ; }, abstract = {BACKGROUND: The purpose of this article was to show that a transposed pyloric valve (PV) can be mobilized to the perianal region and can function as a replacement for an excised rectal sphincter. Surgical research on animals has shown that a vascularized PV can be taken out of gastroduodenal continuity, transposed to the pelvic region with maintenance of fecal control when positioned in the anal area.<br><br>METHODS: The surgical procedure has recently proved successful in humans in which the distal end of the left colon was anastomosed to the proximal end of the transposed PV with the distal end of the PV sutured to the skin in the perianal area as the replacement for an excised rectal sphincter. Fecal control was established after the operation.<br><br>RESULTS: The PV healed in an anal position in humans with no apparent anatomic or physiological reasons to suggest that the operation might not be successful in the future as a substitute for a surgically excised or a severely damaged rectal sphincter.<br><br>CONCLUSIONS: A vascularized PV supplied by the gastroepiploic artery within an omental pedicle can serve as a replacement for an excised rectal sphincter, thus eliminating the need for a permanent colostomy.}, }
@article {pmid21515980, year = {2011}, author = {Almyroudis, NG and Lesse, AJ and Hahn, T and Samonis, G and Hazamy, PA and Wongkittiroch, K and Wang, ES and McCarthy, PL and Wetzler, M and Segal, BH}, title = {Molecular epidemiology and risk factors for colonization by vancomycin-resistant Enterococcus in patients with hematologic malignancies.}, journal = {Infection control and hospital epidemiology}, volume = {32}, number = {5}, pages = {490-496}, doi = {10.1086/659408}, pmid = {21515980}, issn = {1559-6834}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Case-Control Studies ; Child ; Child, Preschool ; Cross Infection/*complications/*epidemiology/transmission ; DNA, Bacterial/analysis ; Electrophoresis, Gel, Pulsed-Field ; Enterococcus/*genetics/isolation &amp; purification ; Female ; Genotype ; Gram-Positive Bacterial Infections/complications/*epidemiology/microbiology/transmission ; Hematologic Neoplasms/*complications ; Humans ; Length of Stay ; Male ; Middle Aged ; Molecular Epidemiology ; Retrospective Studies ; Risk Factors ; *Vancomycin Resistance ; Young Adult ; }, abstract = {OBJECTIVE: To study the molecular epidemiology of vancomycin-resistant Enterococcus (VRE) colonization and to identify modifiable risk factors among patients with hematologic malignancies.<br><br>SETTING: A hematology-oncology unit with high prevalence of VRE colonization.<br><br>PARTICIPANTS: Patients with hematologic malignancies and hematopoietic stem cell transplantation recipients admitted to the hospital.<br><br>METHODS: Patients underwent weekly surveillance by means of perianal swabs for VRE colonization and, if colonized, were placed in contact isolation. We studied the molecular epidemiology in fecal and blood isolates by pulsed-field gel electrophoresis over a 1-year period. We performed a retrospective case-control study over a 3-year period. Cases were defined as patients colonized by VRE, and controls were defined as patients negative for VRE colonization. Case patients and control patients were matched by admitting service and length of observation time.<br><br>RESULTS: Molecular genotyping demonstrated the primarily polyclonal nature of VRE isolates. Colonization occurred at a median of 14 days. Colonized patients were characterized by longer hospital admissions. Previous use of ceftazidime was associated with VRE colonization (P < .001), while use of intravenous vancomycin and antibiotics with anaerobic activity did not emerge as a risk factor. There was no association with neutropenia or presence of colonic mucosal disruption, and severity of illness was similar in both groups.<br><br>CONCLUSION: Molecular studies showed that in the majority of VRE-colonized patients the strains were unique, arguing that VRE acquisition was sporadic rather than resulting from a common source of transmission. Patient-specific factors, including prior antibiotic exposure, rather than breaches in infection control likely predict for risk of fecal VRE colonization.}, }
@article {pmid21505339, year = {2011}, author = {Mercer, DF}, title = {Hot topics in postsmall bowel transplantation: noninvasive graft monitoring including stool calprotectin and plasma citrulline.}, journal = {Current opinion in organ transplantation}, volume = {16}, number = {3}, pages = {316-322}, doi = {10.1097/MOT.0b013e3283467115}, pmid = {21505339}, issn = {1531-7013}, mesh = {Biomarkers/metabolism ; Biopsy ; Citrulline/*blood ; Early Diagnosis ; Feces/*chemistry ; Graft Rejection/*diagnosis/etiology/metabolism ; *Graft Survival ; Humans ; Intestine, Small/metabolism/*transplantation ; Leukocyte L1 Antigen Complex/*metabolism ; *Organ Transplantation/adverse effects ; Predictive Value of Tests ; Reproducibility of Results ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Long-term success in intestinal transplantation could be significantly improved by the development of a reliable noninvasive marker of rejection, allowing early diagnosis and treatment without the need for repeated biopsy procedures.<br><br>RECENT FINDINGS: At present, no single test appears sufficiently reliable to replace the need for invasive testing. Falling plasma citrulline levels may correlate with mucosal damage already done, but do not appear to be specific for rejection or provide clinically useful prediction of an event in advance of its occurrence. Similarly, rising stool calprotectin levels are correlated with pathologic diagnosis of rejection, but do not appear to have sufficient predictive value. Both tests appear to be best described as exclusionary, in that if their values are 'normal', rejection is less likely, but each is hampered by wide variability within and between patients.<br><br>SUMMARY: These approaches and others are reviewed in an outline of the current progress towards developing a clinically useful noninvasive tool for graft monitoring.}, }
@article {pmid21504523, year = {2011}, author = {Saif, MA and Bonney, DK and Bigger, B and Forsythe, L and Williams, N and Page, J and Babiker, ZO and Guiver, M and Turner, AJ and Hughes, S and Wynn, RF}, title = {Chronic norovirus infection in pediatric hematopoietic stem cell transplant recipients: a cause of prolonged intestinal failure requiring intensive nutritional support.}, journal = {Pediatric transplantation}, volume = {15}, number = {5}, pages = {505-509}, doi = {10.1111/j.1399-3046.2011.01500.x}, pmid = {21504523}, issn = {1399-3046}, mesh = {Caliciviridae Infections/*complications/*diagnosis ; Child ; Child, Preschool ; Diarrhea/pathology ; Feces ; Female ; Flow Cytometry/methods ; Gastroenteritis/virology ; Hematopoietic Stem Cell Transplantation/*methods ; Humans ; Immunosuppressive Agents/therapeutic use ; Infant ; Male ; Norovirus/*genetics ; Nutritional Sciences ; Nutritional Support ; RNA, Viral/metabolism ; T-Lymphocytes/cytology ; Transplantation Conditioning/methods ; }, abstract = {Norovirus infection is a major cause of nonbacterial gastroenteritis. In immunocompetent individuals the illness caused by norovirus is mostly self limiting. Excretion of norovirus has been reported to be prolonged in the immunocompromised including adult HSCT recipients. We report a case series of 13 children who received HSCT and required prolonged parenteral and enteral nutrition due to severe gut dysfunction accompanying protracted norovirus excretion that was monitored by RT-PCR. The median duration of viral excretion was 150 days (range 60-380) and the eventual clearance of norovirus from feces was closely associated with donor T cell recovery in the peripheral blood. There was no disease manifestation beyond the gut but the severity and length of norovirus associated illness suggests that HSCT should be delayed where possible in patients excreting the virus prior to conditioning therapy.}, }
@article {pmid21504049, year = {2011}, author = {Vincenzi, R and Neto, JS and Fonseca, EA and Pugliese, V and Leite, KR and Benavides, MR and Cândido, HL and Porta, G and Miura, IK and Pugliese, R and Danesi, VB and Guimarães, TC and Porta, A and Kondo, M and Carone, E and Chapchap, P}, title = {Schistosoma mansoni infection in the liver graft: The impact on donor and recipient outcomes after transplantation.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {17}, number = {11}, pages = {1299-1303}, doi = {10.1002/lt.22316}, pmid = {21504049}, issn = {1527-6473}, mesh = {Biopsy ; Brazil ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Liver/parasitology/pathology/surgery ; Liver Failure/*parasitology/pathology/*surgery ; *Liver Transplantation ; Male ; Retrospective Studies ; Schistosomiasis mansoni/pathology/*surgery ; Tissue Donors ; Treatment Outcome ; }, abstract = {The increasing number of transplants performed each year has led to the identification of unusual diseases in liver grafts from asymptomatic donors that were unrecognized before liver transplantation. Here we report our experience with patients who received liver grafts infected with schistosomiasis. From September 1991 to August 2010, 482 pediatric liver transplants were performed at A. C. Camargo Hospital/Sírio-Libanês Hospital (São Paulo, Brazil). For the identification of Schistosoma mansoni infections, pathology slides for the recipients were reviewed; these included postreperfusion and follow-up liver biopsy samples. We were able to identify 6 cases of schistosomiasis transmitted through infected grafts (5 of these grafts were from living donors). All living donors were confirmed to have normal liver chemistries, negative fecal tests for parasitic diseases, and normal abdominal ultrasound findings. Liver biopsy was not performed before transplantation. In all cases, features of schistosomiasis were absent in the liver explants. The living donors were treated with praziquantel and were taught to avoid risk factors for reinfection. No specific treatment for schistosomiasis was given to the recipients. There were no perioperative deaths, but 2 recipients died after living donor liver transplantation (LDLT) because of Kaposi's sarcoma and non-Hodgkin's lymphoma. In conclusion, using liver grafts infected with S. mansoni eggs did not compromise the results of LDLT in this pediatric cohort. Because of the parasite's life cycle and the therapeutic target of praziquantel, only donors should be treated for the infection. Three years of follow-up showed an uneventful recovery for the living donors.}, }
@article {pmid21502971, year = {2011}, author = {Surawicz, CM and Alexander, J}, title = {Treatment of refractory and recurrent Clostridium difficile infection.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {8}, number = {6}, pages = {330-339}, pmid = {21502971}, issn = {1759-5053}, mesh = {*Clostridioides difficile ; Colectomy ; Enterocolitis, Pseudomembranous/*epidemiology/*therapy ; Humans ; Metronidazole/therapeutic use ; Recurrence ; Severity of Illness Index ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {The incidence of Clostridium difficile infection (CDI) has increased since 2000, with greater numbers of severe cases reported, in part due to the emergence of a hypervirulent strain. Initial therapy with metronidazole is still recommended for mild to moderate CDI, but vancomycin is recommended for first-line therapy of severe CDI. Colectomy could be life-saving for some patients with severe disease that does not respond to maximal medical therapy. Recurrent CDI is a challenge to treat; no single effective therapy currently exists. Treatments include antibiotics, adjunct probiotics, fecal microbiota transplant and immune approaches. This Review discusses the various therapeutic approaches used for the treatment of refractory and recurrent CDI.}, }
@article {pmid21487110, year = {2011}, author = {Schwartz, S and Vergoulidou, M and Schreier, E and Loddenkemper, C and Reinwald, M and Schmidt-Hieber, M and Flegel, WA and Thiel, E and Schneider, T}, title = {Norovirus gastroenteritis causes severe and lethal complications after chemotherapy and hematopoietic stem cell transplantation.}, journal = {Blood}, volume = {117}, number = {22}, pages = {5850-5856}, pmid = {21487110}, issn = {1528-0020}, support = {Z99 CL999999//Intramural NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Caliciviridae Infections/diagnosis/*etiology/prevention &amp; control ; Combined Modality Therapy ; DNA, Viral/genetics ; Disease Outbreaks ; Feces/virology ; Female ; Gastroenteritis/diagnosis/*etiology/prevention &amp; control ; Hematologic Diseases/*complications/therapy/virology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Norovirus/genetics/*isolation &amp; purification ; Polymerase Chain Reaction ; Survival Rate ; Treatment Outcome ; Young Adult ; }, abstract = {Norovirus (NV) infections are a frequent cause of gastroenteritis (GE), but data on this disease in immunocompromised patients are limited. We analyzed an NV outbreak, which affected immunosuppressed patients in the context of chemotherapy or HSCT. On recognition, 7 days after admission of the index patient, preventive measures were implemented. Attack rates were only 3% (11/334) and 10% (11/105) among patients and staff members, respectively. The median duration of symptoms was 7 days in patients compared with only 3 days in staff members (P = .02). Three patients died of the NV infection. Commonly used clinical diagnostic criteria (Kaplan-criteria) were unsuitable because they applied to 11 patients with proven NV-GE but also to 15 patients without NV-GE. With respect to the therapeutic management, it is important to differentiate intestinal GVHD from NV-GE. Therefore, we analyzed the histopathologic patterns in duodenal biopsies, which were distinctive in both conditions. Stool specimens in patients remained positive for NV-RNA for a median of 30 days, but no transmission was observed beyond an asymptomatic interval of 48 hours. NV-GE is a major threat to patients with chemotherapy or HSCT, and meticulous measures are warranted to prevent transmission of NV to these patients.}, }
@article {pmid21481083, year = {2011}, author = {Jeulin, H and Salmon, A and Bordigoni, P and Venard, V}, title = {Diagnostic value of quantitative PCR for adenovirus detection in stool samples as compared with antigen detection and cell culture in haematopoietic stem cell transplant recipients.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {17}, number = {11}, pages = {1674-1680}, doi = {10.1111/j.1469-0691.2011.03488.x}, pmid = {21481083}, issn = {1469-0691}, mesh = {Adenoviridae Infections/*diagnosis/virology ; Adenoviruses, Human/genetics/*isolation &amp; purification ; Adolescent ; Adult ; Antigens, Viral/analysis ; Child, Preschool ; Clinical Laboratory Techniques/*methods ; DNA, Viral/genetics/isolation &amp; purification ; Feces/*virology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Infant ; Male ; Mass Screening/methods ; Middle Aged ; Real-Time Polymerase Chain Reaction/*methods ; Retrospective Studies ; Sensitivity and Specificity ; Transplantation ; Viral Load/methods ; Virology/*methods ; Virus Cultivation ; Young Adult ; }, abstract = {Adenovirus (AdV) infections constitute a significant cause of morbidity and mortality during haematopoietic stem cell transplantation. Recent guidelines recommend repeated screening for AdV in whole blood (WB), with quantitative PCR (qPCR) as the reference standard. Despite pre-emptive antiviral treatment based on qPCR in WB, the mortality rate after disseminated AdV infection remains very high. The aim of our study was to advance early screening for AdV, using a standardized method, so as to enable the earlier initiation of antiviral treatment or adoptive immunotherapy. The diagnostic value of AdV DNA quantification in stool samples was investigated retrospectively and compared with antigen detection and cell culture in 21 patients with AdV infection, from 182 patients followed in the Transplant Unit of Nancy University Hospital Centre, including 18 patients with systemic infection. In 16/18 patients with positive AdV viraemia, AdV DNA was present in stool samples earlier than in WB (median, 42 days; range, 3-199 days), whereas both antigen detection and cell culture were still negative for 11/18 patients with systemic AdV infection. The course of AdV viral loads in stool samples was predictive of adenoviraemia (sensitivity, 89%). Very late and lethal AdV infections were observed in cord blood transplant recipients, and would have been detected much earlier with the use of qPCR on stool samples. This study confirmed that quantification of AdV in stool samples by qPCR is beneficial for the management of transplant recipients, with or without antigen detection.}, }
@article {pmid21467934, year = {2011}, author = {Matsumoto, CS and Kaufman, SS and Fishbein, TM}, title = {Inclusion of the colon in intestinal transplantation.}, journal = {Current opinion in organ transplantation}, volume = {16}, number = {3}, pages = {312-315}, doi = {10.1097/MOT.0b013e3283467102}, pmid = {21467934}, issn = {1531-7013}, mesh = {Colon/metabolism/physiopathology/*transplantation ; Defecation ; Graft Survival ; Humans ; Intestinal Absorption ; Intestinal Diseases/metabolism/physiopathology/*surgery ; *Organ Transplantation/adverse effects ; Parenteral Nutrition ; Quality of Life ; Risk Assessment ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Inclusion of the colon as a component of an intestinal graft has evolved over the past two decades. Initially thought to be hazardous and abandoned by many centers, colon inclusion has now proven to be an integral component of the intestinal transplant graft.The purpose of this review is to summarize the history of colon inclusion, the physiology of the colon, surgical techniques of colon inclusion, and outcome data.<br><br>RECENT FINDINGS: Recent studies at centers of excellence report the efficacy and safety of colon inclusion in intestinal transplantation. Quality-of-life indicators, stool patterns, fecal continence, and parenteral nutrition weaning were noted to be improved in recipients of colonic inclusion. Complex intestinal transplant case series were reported with no adverse effects of colon inclusion.<br><br>SUMMARY: Colon inclusion provides a necessary function in intestinal transplantation by taking advantages of its physiologic functions of water absorption, residue breakdown, and storage. Current clinical evidence supports the efficacy of selective and cautious use of the colon in intestinal transplantation.}, }
@article {pmid21463628, year = {2011}, author = {Raghavan, S and Gilmont, RR and Miyasaka, EA and Somara, S and Srinivasan, S and Teitelbaum, DH and Bitar, KN}, title = {Successful implantation of bioengineered, intrinsically innervated, human internal anal sphincter.}, journal = {Gastroenterology}, volume = {141}, number = {1}, pages = {310-319}, pmid = {21463628}, issn = {1528-0012}, support = {R01DK071614/DK/NIDDK NIH HHS/United States ; T32 HD007505-13/HD/NICHD NIH HHS/United States ; 1RC1DK087151/DK/NIDDK NIH HHS/United States ; R01 DK080684-03/DK/NIDDK NIH HHS/United States ; T32HD007505/HD/NICHD NIH HHS/United States ; RC1 DK087151/DK/NIDDK NIH HHS/United States ; R01 DK080684/DK/NIDDK NIH HHS/United States ; R01 DK071614-05/DK/NIDDK NIH HHS/United States ; R01DK080684/DK/NIDDK NIH HHS/United States ; R01 DK071614/DK/NIDDK NIH HHS/United States ; T32 HD007505/HD/NICHD NIH HHS/United States ; RC1 DK087151-02/DK/NIDDK NIH HHS/United States ; }, mesh = {Anal Canal/blood supply/drug effects/*innervation/*transplantation ; Animals ; *Bioartificial Organs ; Cells, Cultured ; Cholinergic Agonists/pharmacology ; Coculture Techniques ; Electric Stimulation ; Enzyme Inhibitors/pharmacology ; Gastrointestinal Motility ; *Graft Survival ; Homeodomain Proteins/genetics/metabolism ; Hormone Antagonists/pharmacology ; Humans ; Mice ; Mice, Knockout ; Muscle Contraction ; Muscle Relaxation ; Muscle, Smooth/blood supply/drug effects/*innervation/*transplantation ; Neovascularization, Physiologic ; Nitric Oxide Synthase/antagonists &amp; inhibitors/metabolism ; Receptors, Vasoactive Intestinal Peptide/antagonists &amp; inhibitors/metabolism ; Time Factors ; Tissue Engineering/*methods ; Transplantation, Heterologous ; Vasoactive Intestinal Peptide/metabolism ; }, abstract = {BACKGROUND &amp; AIMS: To restore fecal continence, the weakened pressure of the internal anal sphincter (IAS) must be increased. We bioengineered intrinsically innervated human IAS to emulate sphincteric physiology in vitro.<br><br>METHODS: We cocultured human IAS circular smooth muscle with immortomouse fetal enteric neurons. We investigated the ability of bioengineered innervated human IAS, implanted in RAG1-/- mice, to undergo neovascularization and preserve the physiology of the constituent myogenic and neuronal components.<br><br>RESULTS: The implanted IAS was neovascularized in vivo; numerous blood vessels were observed with no signs of inflammation or infection. Real-time force acquisition from implanted and preimplant IAS showed distinct characteristics of IAS physiology. Features included the development of spontaneous myogenic basal tone; relaxation of 100% of basal tone in response to inhibitory neurotransmitter vasoactive intestinal peptide (VIP) and direct electrical field stimulation of the intrinsic innervation; inhibition of nitrergic and VIPergic electrical field-induced relaxation (by antagonizing nitric oxide synthesis or receptor interaction); contraction in response to cholinergic stimulation with acetylcholine; and intact electromechanical coupling (evidenced by direct response to potassium chloride). Implanted, intrinsically innervated bioengineered human IAS tissue preserved the integrity and physiology of myogenic and neuronal components.<br><br>CONCLUSIONS: Intrinsically innervated human IAS bioengineered tissue can be successfully implanted in mice. This approach might be used to treat patients with fecal incontinence.}, }
@article {pmid21460762, year = {2011}, author = {Mercer, DF and Vargas, L and Sun, Y and Moreno, AM and Grant, WJ and Botha, JF and Langnas, AN and Sudan, DL}, title = {Stool calprotectin monitoring after small intestine transplantation.}, journal = {Transplantation}, volume = {91}, number = {10}, pages = {1166-1171}, doi = {10.1097/TP.0b013e318215e709}, pmid = {21460762}, issn = {1534-6080}, mesh = {Adolescent ; Analysis of Variance ; Biopsy ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Feces/*chemistry ; Female ; Graft Rejection/*diagnosis/etiology/metabolism ; Humans ; Infant ; Intestine, Small/*transplantation ; Leukocyte L1 Antigen Complex/*metabolism ; Male ; Nebraska ; Organ Transplantation/adverse effects ; Predictive Value of Tests ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Small intestine transplantation is the only life-saving therapy available for patients with intestinal failure and life-threatening complications of parenteral nutrition, but it is still plagued by high levels of early acute rejection. The ability to diagnose rejection noninvasively, ideally before pathologic manifestations, would be a major advance in the care of intestinal transplant patients.<br><br>METHODS: We measured calprotectin levels in 732 stool samples collected, analyzed over from 72 patients having undergone 74 total transplants, and correlated them with clinical indications, ostomy output, and pathologic findings.<br><br>RESULTS: We found that overall patients with rejection have higher mean levels of stool calprotectin than those without, but because of significant interpatient variability, defining an effective general "cutoff" for the test is difficult. Each patient, in effect, has to act as their own control. Patients experiencing rejection episodes have greater fluctuations in calprotectin levels than those without, suggesting increased "reactivity" within the graft. Our most frequent clinical indicator for biopsy, an increase in ostomy output, had no real relationship to the discovery of rejection.<br><br>CONCLUSION: Although more frequent prospective sampling could perhaps demonstrate an advantage in early indication of rejection, based on these data, routine stool calprotectin monitoring is not strongly supported.}, }
@article {pmid21458513, year = {2011}, author = {Aggarwal, R}, title = {Clinical presentation of hepatitis E.}, journal = {Virus research}, volume = {161}, number = {1}, pages = {15-22}, doi = {10.1016/j.virusres.2011.03.017}, pmid = {21458513}, issn = {1872-7492}, mesh = {Female ; Global Health ; Hepatitis E/complications/*epidemiology/transmission/virology ; Hepatitis E virus/genetics/*physiology ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Male ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology/virology ; }, abstract = {Hepatitis E is a form of acute hepatitis, which is caused by infection with hepatitis E virus. The infection is transmitted primarily through fecal-oral route and the disease is highly endemic in several developing countries with opportunities for contamination of drinking water. In these areas with high endemicity, it occurs as outbreaks and as sporadic cases of acute hepatitis. The illness often resembles that associated with other hepatotropic viruses and is usually self-limiting; in some cases, the disease progresses to acute liver failure. The infection is particularly severe in pregnant women. Patients with chronic liver disease and superimposed HEV infection can present with severe liver injury, the so-called acute-on-chronic liver failure. In recent years, occasional sporadic cases with locally acquired hepatitis E have been reported from several developed countries in Europe, United States, and Asia. In these areas, in addition to acute hepatitis similar to that seen in highly endemic areas, chronic hepatitis E has been reported among immunosuppressed persons, in particular solid organ transplant recipients. HEV-infected mothers can transmit the infection to foetus, leading to premature birth, increased fetal loss and hypoglycaemia, hypothermia, and anicteric or icteric acute hepatitis in the newborns. Occasional cases with atypical non-hepatic manifestations, such as acute pancreatitis, hematological abnormalities, autoimmune phenomena, and neurological syndromes have been reported from both hyperendemic and non-endemic regions. The pathogenesis of these manifestations remains unclear.}, }
@article {pmid21453182, year = {2011}, author = {Briscoe, JA and Bennett, RA}, title = {Use of a duodenal serosal patch in the repair of a colon rupture in a female Solomon Island eclectus parrot.}, journal = {Journal of the American Veterinary Medical Association}, volume = {238}, number = {7}, pages = {922-926}, doi = {10.2460/javma.238.7.922}, pmid = {21453182}, issn = {0003-1488}, mesh = {Animals ; Bird Diseases/*surgery ; Colon/*injuries/surgery ; Digestive System Surgical Procedures/methods/*veterinary ; Female ; Parrots ; Rupture/surgery/*veterinary ; Serous Membrane/*transplantation ; Surgical Flaps/veterinary ; Wound Healing ; }, abstract = {Case Description-A 444-g (0.98-lb) 4-year-old sexually intact female Solomon Island eclectus parrot (Eclectus roratus solomonensis) was referred and evaluated for a suspected colonic obstruction. Clinical Findings-The parrot had a 3-day history of not passing feces and lack of appetite following treatment of dystocia that included percutaneous collapse of the egg and manual removal of egg fragments via the cloaca. During this procedure, a tear in the cloacal mucosa developed. The tear was repaired via a midline cloacotomy. Although clinically stable at the time of referral, the parrot became lethargic and bradycardic and had delayed crop emptying. Treatment and Outcome-A midline celiotomy and cloacotomy were performed to relieve the colonic obstruction, during which the severely distended colon ruptured. The colonic defects were closed in a simple interrupted pattern, and a serosal patch was applied by use of the adjacent duodenum. The bird recovered uneventfully from anesthesia and was passing voluminous feces with mildly increased effort within 1 hour after surgery. At 3 weeks after surgery, the parrot was passing feces with no increase in effort and had a normal appetite. Clinical Relevance-Application of a duodenal serosal patch for repair of a colon rupture was successful in this parrot. Gastrointestinal obstruction is rare in birds, but should be considered in birds that have regurgitation, decreased fecal production, and gastrointestinal dilation. Because birds lack an omentum, serosal patching with adjacent duodenum should be considered as a viable option in avian surgery.}, }
@article {pmid21436049, year = {2011}, author = {Goodman, AL and Kallstrom, G and Faith, JJ and Reyes, A and Moore, A and Dantas, G and Gordon, JI}, title = {Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108}, number = {15}, pages = {6252-6257}, pmid = {21436049}, issn = {1091-6490}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK030292/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; K01DK089121/DK/NIDDK NIH HHS/United States ; DK30292/DK/NIDDK NIH HHS/United States ; F32AI078628/AI/NIAID NIH HHS/United States ; F32 AI078628/AI/NIAID NIH HHS/United States ; DK70977/DK/NIDDK NIH HHS/United States ; T32-HD043010/HD/NICHD NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; K01 DK089121/DK/NIDDK NIH HHS/United States ; T32 HD043010/HD/NICHD NIH HHS/United States ; DK78669/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*classification/isolation &amp; purification ; Cell Culture Techniques ; Feces/microbiology ; Gastrointestinal Tract/*microbiology ; *Germ-Free Life ; Humans ; *Metagenome ; Mice ; Phylogeny ; }, abstract = {The proportion of the human gut bacterial community that is recalcitrant to culture remains poorly defined. In this report, we combine high-throughput anaerobic culturing techniques with gnotobiotic animal husbandry and metagenomics to show that the human fecal microbiota consists largely of taxa and predicted functions that are represented in its readily cultured members. When transplanted into gnotobiotic mice, complete and cultured communities exhibit similar colonization dynamics, biogeographical distribution, and responses to dietary perturbations. Moreover, gnotobiotic mice can be used to shape these personalized culture collections to enrich for taxa suited to specific diets. We also demonstrate that thousands of isolates from a single donor can be clonally archived and taxonomically mapped in multiwell format to create personalized microbiota collections. Retrieving components of a microbiota that have coexisted in single donors who have physiologic or disease phenotypes of interest and reuniting them in various combinations in gnotobiotic mice should facilitate preclinical studies designed to determine the degree to which tractable bacterial taxa are able to transmit donor traits or influence host biology.}, }
@article {pmid21398226, year = {2011}, author = {Glauser, W}, title = {Risk and rewards of fecal transplants.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {183}, number = {5}, pages = {541-542}, doi = {10.1503/cmaj.109-3806}, pmid = {21398226}, issn = {1488-2329}, mesh = {Chronic Disease ; Clostridioides difficile/isolation &amp; purification ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Feces ; Humans ; Risk Assessment ; Transplants ; Treatment Outcome ; }, }
@article {pmid21390141, year = {2011}, author = {Motoki, T and Naomoto, Y and Hoshiba, J and Shirakawa, Y and Yamatsuji, T and Matsuoka, J and Takaoka, M and Tomono, Y and Fujiwara, Y and Tsuchita, H and Gunduz, M and Nagatsuka, H and Tanaka, N and Fujiwara, T}, title = {Glutamine depletion induces murine neonatal melena with increased apoptosis of the intestinal epithelium.}, journal = {World journal of gastroenterology}, volume = {17}, number = {6}, pages = {717-726}, pmid = {21390141}, issn = {2219-2840}, mesh = {Animals ; *Animals, Newborn ; Apoptosis/*physiology ; Cell Line ; Cell Proliferation ; Colon/pathology ; *Diet ; Epithelial Cells/metabolism/ultrastructure ; Female ; Glutamine/administration &amp; dosage/*deficiency ; Hemorrhage ; Humans ; Intestinal Mucosa/cytology/*pathology ; Melena/*metabolism ; Mice ; Pregnancy ; Rats ; }, abstract = {AIM: To investigate the possible biological outcome and effect of glutamine depletion in neonatal mice and rodent intestinal epithelial cells.<br><br>METHODS: We developed three kinds of artificial milk with different amounts of glutamine; Complete amino acid milk (CAM), which is based on maternal mouse milk, glutamine-depleted milk (GDM), and glutamine-rich milk (GRM). GRM contains three-fold more glutamine than CAM. Eighty-seven newborn mice were divided into three groups and were fed with either of CAM, GDM, or GRM via a recently improved nipple-bottle system for seven days. After the feeding period, the mice were subjected to macroscopic and microscopic observations by immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU) and Ki-67 as markers of cell proliferation, and for cleaved-caspase-3 as a marker of apoptosis. Moreover, IEC6 rat intestinal epithelial cells were cultured in different concentrations of glutamine and were subject to a 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate cell proliferation assay, flow cytometry, and western blotting to examine the biological effect of glutamine on cell growth and apoptosis.<br><br>RESULTS: During the feeding period, we found colonic hemorrhage in six of 28 GDM-fed mice (21.4%), but not in the GRM-fed mice, with no differences in body weight gain between each group. Microscopic examination showed destruction of microvilli and the disappearance of glycocalyx of the intestinal wall in the colon epithelial tissues taken from GDM-fed mice. Intake of GDM reduced BrdU incorporation (the average percentage of BrdU-positive staining; GRM: 13.8%, CAM: 10.7%, GDM: 1.14%, GRM vs GDM: P < 0.001, CAM vs GDM: P < 0.001) and Ki-67 labeling index (the average percentage of Ki-67-positive staining; GRM: 24.5%, CAM: 22.4% GDM: 19.4%, GRM vs GDM: P = 0.001, CAM vs GDM: P = 0.049), suggesting that glutamine depletion inhibited cell proliferation of intestinal epithelial cells. Glutamine deprivation further caused the deformation of the nuclear membrane and the plasma membrane, accompanied by chromatin degeneration and an absence of fat droplets from the colonic epithelia, indicating that the cells underwent apoptosis. Moreover, immunohistochemical analysis revealed the appearance of cleaved caspase-3 in colonic epithelial cells of GDM-fed mice. Finally, when IEC6 rat intestinal epithelial cells were cultured without glutamine, cell proliferation was significantly suppressed after 24 h (relative cell growth; 4 mmol/L: 100.0% &#xb1; 36.1%, 0 mmol/L: 25.3% &#xb1; 25.0%, P < 0.05), with severe cellular damage. The cells underwent apoptosis, accompanied by increased cell population in sub-G0 phase (4 mmol/L: 1.68%, 0.4 mmol/L: 1.35%, 0 mmol/L: 5.21%), where dying cells are supposed to accumulate.<br><br>CONCLUSION: Glutamine is an important alimentary component for the maintenance of intestinal mucosa. Glutamine deprivation can cause instability of the intestinal epithelial alignment by increased apoptosis.}, }
@article {pmid21385859, year = {2011}, author = {Struijk, GH and Gijsen, AF and Yong, SL and Zwinderman, AH and Geerlings, SE and Lettinga, KD and van Donselaar-van der Pant, KA and ten Berge, IJ and Bemelman, FJ}, title = {Risk of Pneumocystis jiroveci pneumonia in patients long after renal transplantation.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {26}, number = {10}, pages = {3391-3398}, doi = {10.1093/ndt/gfr048}, pmid = {21385859}, issn = {1460-2385}, mesh = {Adult ; Aged ; Anti-Infective Agents/therapeutic use ; Case-Control Studies ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Immunosuppressive Agents/therapeutic use ; Kidney Failure, Chronic/*complications/therapy ; Kidney Function Tests ; Kidney Transplantation/*adverse effects ; Lymphocyte Count ; Lymphopenia/diagnosis/*etiology ; Male ; Middle Aged ; Pneumocystis Infections/*etiology ; Pneumocystis carinii/*isolation &amp; purification ; Prognosis ; Retrospective Studies ; Risk Factors ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use ; }, abstract = {BACKGROUND: Pneumocystis jiroveci pneumonia (PCP) is an important cause of morbidity and mortality in renal transplant recipients (RTRs). Chemoprophylaxis with trimethoprim/sulphamethoxazole is recommended during the early post-transplantation period, but the optimal duration has not been determined and a main drawback of chemoprophylaxis is the development of resistance of the commensal faecal flora. A cluster outbreak of PCP occurred in our outpatient Renal Transplant Unit. We aimed to investigate risk factors for PCP in RTRs to determine who should receive long-term chemoprophylaxis.<br><br>METHODS: In a case-control study, we investigated common demographic variables and immunological parameters. Nine PCP cases diagnosed between August 2006 and April 2007 were matched with 18 control patients, who did not develop PCP, received their transplant in the same time-period and had a similar follow-up period with a comparable immunosuppressive drug regimen.<br><br>RESULTS: The median time from transplantation to PCP was 19 months. We observed no significant differences in gender, age, donor type or number of rejections. In PCP cases, the median lymphocyte count just before PCP diagnosis was 0.49 (0.26-0.68), which was significantly reduced compared to the control patients after a similar follow-up period (median 1.36, 0.59-3.04, P = 0.002). This lymphocytopaenia was chronic and existed in most patients already for many months. CD4(+) T-cell counts were also significantly reduced in the PCP cases. We found no difference in the Th1, Th2 and Th17 subsets between PCP cases and control patients.<br><br>CONCLUSION: Long-term prophylactic therapy for PCP may be indicated for RTR with persistent severe lymphocytopaenia.}, }
@article {pmid21377021, year = {2011}, author = {Samplaski, MK and Wood, HM and Lane, BR and Remzi, FH and Lucas, A and Angermeier, KW}, title = {Functional and quality-of-life outcomes in patients undergoing transperineal repair with gracilis muscle interposition for complex rectourethral fistula.}, journal = {Urology}, volume = {77}, number = {3}, pages = {736-741}, doi = {10.1016/j.urology.2010.08.009}, pmid = {21377021}, issn = {1527-9995}, mesh = {Adult ; Aged ; Fecal Incontinence/etiology ; Humans ; Middle Aged ; Muscle, Skeletal/*transplantation ; Postoperative Complications ; *Quality of Life ; Plastic Surgery Procedures/adverse effects/methods ; Rectal Fistula/etiology/*surgery ; Urethral Diseases/etiology/*surgery ; Urinary Fistula/etiology/*surgery ; Urinary Incontinence/etiology ; Urologic Surgical Procedures/adverse effects/methods ; }, abstract = {OBJECTIVE: To evaluate the results and quality of life outcomes of transperineal repair using gracilis muscle interposition in patients who were candidates for attempted preservation of bowel and bladder function. There is currently no widely accepted procedure for the treatment of complex RUF, such as those complicated by radiotherapy, previous attempts at repair, or large in size.<br><br>METHODS: Thirteen patients who underwent transperineal repair with gracilis muscle interposition for complex RUF were identified. Records were reviewed for fistula etiology, prior repair, intraoperative findings, hospital course, complications, diversion reversal, and outcome. Follow-up data were gathered from clinic visits and questionnaires.<br><br>RESULTS: Preoperative diagnoses included: prostate cancer (PCA) (12) and imperforate anus (1). Treatment for PCA included radical prostatectomy (4); brachytherapy (BT) (3); external beam radiation therapy (EBRT) + BT (3); cryoablation (1); and EBRT + cryoablation (1). Five patients underwent prior unsuccessful repair. There were no intraoperative complications. Postoperative complications included fecal incontinence (3) and bladder neck contracture (1). Nine patients (75%) reported some degree of urinary incontinence, with 2 patients reporting this as significant, defined as incontinence "most of the time." Suprapubic catheters were removed after 6 weeks, and median stomal reversal was at 17.5 weeks (12-28). One patient developed a recurrent RUF. All patients completed quality-of-life questionnaires assessing urinary and fecal outcome. Fecal outcome measures were generally better than urinary, but both were reasonable given the complexity of the situation.<br><br>CONCLUSIONS: Transperineal repair with gracilis muscle interposition is an effective treatment for selected patients with complex RUF. Our experience demonstrates low morbidity, high success rates, and reasonable bowel and bladder function postoperatively.}, }
@article {pmid21297602, year = {2011}, author = {Palmer, R}, title = {Fecal matters.}, journal = {Nature medicine}, volume = {17}, number = {2}, pages = {150-152}, pmid = {21297602}, issn = {1546-170X}, mesh = {Clostridioides difficile ; Colon/microbiology ; Enterocolitis, Pseudomembranous/therapy ; *Feces ; Gastrointestinal Diseases/*therapy ; Humans ; Intestines/microbiology ; Transplantation, Homologous ; }, }
@article {pmid21287220, year = {2011}, author = {Abbes Orabi, N and Paterson, HM and Goncette, L and Danse, E and Saey, JP and Kartheuser, A}, title = {Malone appendicostomy: an unexpected complication.}, journal = {Techniques in coloproctology}, volume = {15}, number = {1}, pages = {81-83}, pmid = {21287220}, issn = {1128-045X}, mesh = {Fecal Impaction/*surgery ; Fecal Incontinence/therapy ; Female ; Humans ; Middle Aged ; Surgical Stomas/*adverse effects ; }, abstract = {The Malone appendicostomy is a novel option for surgical management of faecal incontinence and chronic constipation, by permitting the administration of antegrade colonic enemas for colonic evacuation. We report the case of a 54-year-old female who had undergone abdomino perineal resection for low rectal cancer followed by total perineal reconstruction with perineal colostomy, dynamic double graciloplasty and Malone appendicostomy. After 7-year follow-up, functional results and quality of life scores were satisfactory. Suddenly the patient described increasing difficulty with intubation of her appendicostomy and complete reflux of the enema liquid, which radiology referred to a calcified body of 35 mm within the Malone appendicostomy causing nearly complete obstruction of the conduit. A surgical exploration was necessary to extract the fecolith allowing full recovery with return to satisfactory Malone appendicostomy function. To our knowledge, this is the first report of a fecolith causing obstruction within a Malone appendicostomy.}, }
@article {pmid21278582, year = {2011}, author = {Ho, N and Prasad, V}, title = {Lacking the incentive to cure? Recurring Clostridium difficile diarrhea and our reluctance to use fecal transplantation.}, journal = {Journal of clinical gastroenterology}, volume = {45}, number = {4}, pages = {379-380}, doi = {10.1097/MCG.0b013e318202ad8e}, pmid = {21278582}, issn = {1539-2031}, mesh = {Antibodies, Monoclonal/immunology/therapeutic use ; Bacterial Toxins/immunology ; *Clostridioides difficile/immunology ; Diarrhea/therapy ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; *Secondary Prevention ; Tissue Donors ; Transplantation/*methods/*statistics &amp; numerical data ; }, }
@article {pmid21268362, year = {2010}, author = {Kulikov, DA and Mashkov, AE and Kulikov, AV and Shumskiĭ, VI}, title = {[Compensation of the rectum muscle dysfunction].}, journal = {Biofizika}, volume = {55}, number = {6}, pages = {1147-1148}, pmid = {21268362}, issn = {0006-3029}, mesh = {Anal Canal/physiopathology/surgery ; Animals ; *Bone Marrow Transplantation ; Disease Models, Animal ; Fecal Incontinence/pathology/physiopathology/*surgery ; Muscle, Smooth/pathology/physiopathology/*surgery ; Rats ; Rats, Wistar ; Rectum/pathology/physiopathology/*surgery ; }, abstract = {The possibility of compensating for the inborn pathology of the obturative apparatus of the rectum has been examined. An adequate experimental model of encopresis and a method of transplantological compensation of this pathological state have been developed.}, }
@article {pmid21265253, year = {2010}, author = {Zailani, MH and Azmi, MN and Deen, KI}, title = {Gracilis muscle as neoanal sphincter for faecal incontinence.}, journal = {The Medical journal of Malaysia}, volume = {65}, number = {1}, pages = {66-67}, pmid = {21265253}, issn = {0300-5283}, mesh = {Adult ; Electric Stimulation Therapy/*methods ; Fecal Incontinence/*surgery ; Humans ; Male ; Muscle, Skeletal/innervation/*transplantation ; }, abstract = {Faecal incontinence is a debilitating chronic clinical condition which may affect the patient and care givers. Modality of treatment is based on severity of the symptoms as well as the anatomical defect itself, availability of resources and expertise. We describe a modified technique of dynamic graciloplasty as neoanal sphincter for the treatment severe faecal incontinence who has failed previous over lapping sphincteroplasty. In our modified version, instead of using implanted intramuscular electrodes and subcutaneous neurostimulator to provide continuous stimulation, the patient will undergo an external stimulation on the nerve of transplanted gracilis periodically and concurrent biofeedback therapy. We believe the technique is relatively easy to learn and very cost effective without any electrodes or neurostimulator related complications.}, }
@article {pmid21212401, year = {2011}, author = {Lee-Rueckert, M and Silvennoinen, R and Rotllan, N and Judström, I and Blanco-Vaca, F and Metso, J and Jauhiainen, M and Kovanen, PT and Escola-Gil, JC}, title = {Mast cell activation in vivo impairs the macrophage reverse cholesterol transport pathway in the mouse.}, journal = {Arteriosclerosis, thrombosis, and vascular biology}, volume = {31}, number = {3}, pages = {520-527}, doi = {10.1161/ATVBAHA.110.221069}, pmid = {21212401}, issn = {1524-4636}, mesh = {Animals ; Apolipoprotein A-I/administration &amp; dosage/metabolism ; Biological Transport ; *Cell Communication/drug effects ; *Cell Degranulation/drug effects ; Cell Line ; Cholesterol/*metabolism ; Chymases/*metabolism ; Feces/chemistry ; Foam Cells/metabolism ; Humans ; Injections, Intraperitoneal ; Macrophages/*metabolism/transplantation ; Mast Cells/drug effects/*enzymology ; Mice ; Mice, Inbred C57BL ; Mutation ; Phospholipids/administration &amp; dosage ; Protein Denaturation ; Proto-Oncogene Proteins c-kit/genetics ; Time Factors ; Tritium ; p-Methoxy-N-methylphenethylamine/administration &amp; dosage ; }, abstract = {OBJECTIVE: Chymase released by activated mast cells degrades high-density lipoproteins. We evaluated whether local activation of mast cells would attenuate cholesterol efflux from neighboring macrophage foam cells, thereby disrupting the entire in vivo pathway of macrophage-specific reverse cholesterol transport (RCT).<br><br>METHODS AND RESULTS: C57Bl/6J mice received intraperitoneal injections of the mast cell-degranulating compound 48/80 to induce peritoneal mast cell activation, human apolipoprotein A-I (apoA-I) to stimulate RCT, and [(3)H]cholesterol-labeled J774 macrophages for measurement of the rate of RCT. After 3 hours, (3)H-radioactivity was measured in the intestinal lumen contents. Activation of mast cells in the peritoneal cavity depleted human apoA-I pre-&#x3b2;-migrating species, impairing the ability of the peritoneal fluid to efficiently promote cholesterol efflux from cultured macrophages. Moreover, intact but not chymase-treated (proteolyzed) apoA-I accelerated the transfer of macrophage-derived (3)H- radioactivity to the intestinal contents. Importantly, stimulation of RCT by human apoA-I was fully blocked by 48/80 in mast cell-competent wild-type C57Bl/6J mice but not in mast cell-deficient W-sash c-kit mutant mice. The ability of intraperitoneally administered phospholipid vesicles to promote RCT in wild-type mice was not blocked by 48/80, supporting the notion that mast cell-dependent proteolysis of the intraperitoneally administered apoA-I was responsible for RCT inhibition.<br><br>CONCLUSIONS: Overall, our results suggest that tissue-specific activation of mast cells with ensuing release of chymase is able to proteolytically inactivate apoA-I in the microenvironment of the activated mast cells, thus locally impairing the initiation of macrophage RCT in vivo.}, }
@article {pmid24968601, year = {2011}, author = {Khainga, SO and Tenge, RK and Kituyi, PW}, title = {Restoration of anal sphincter tone by graciloplasty: a report of five cases.}, journal = {East African medical journal}, volume = {88}, number = {1}, pages = {33-36}, pmid = {24968601}, issn = {0012-835X}, mesh = {Adolescent ; Anal Canal/physiopathology/*surgery ; Child ; Exercise Therapy ; Fecal Incontinence/etiology/rehabilitation/*surgery ; Female ; Humans ; Male ; Muscle Tonus ; Muscle, Skeletal/*transplantation ; Surgically-Created Structures/*physiology ; }, abstract = {Stool incontinence can be as a result of congenital or acquired anal sphincter problems. It is a devastating state for a patient not to be able to control stools resulting into continued feacal soiling. It reduces an individual to a dejected and depressed person who becomes a social misfit. Hence any procedure that can alleviate this state is normally highly appreciated. Various techniques have been quoted in literature and use of gracilis muscle to form a neosphincter is one of them. Dynamic graciloplasty, is a technique whereby electrodes have been implanted into gracilis muscle and is connected to an implantable pulse generator which provides progressive levels of stimulation to convert the fast twitch, fatigue prone muscle fibres to a slow twitch, fatigue resistant firbres over eight week training period (1,2,3). This has shown improved efficacy over the static graciloplasty (3). In this case report, five patients with stool incontinence from different aetiologies are presented, all having been managed by static graciloplasty and intense physiotherapy with good outcomes reported.}, }
@article {pmid21187173, year = {2011}, author = {Ahmadi, R and Mordan, N and Forbes, A and Day, RM}, title = {Enhanced attachment, growth and migration of smooth muscle cells on microcarriers produced using thermally induced phase separation.}, journal = {Acta biomaterialia}, volume = {7}, number = {4}, pages = {1542-1549}, doi = {10.1016/j.actbio.2010.12.022}, pmid = {21187173}, issn = {1878-7568}, support = {//Department of Health/United Kingdom ; }, mesh = {Animals ; Cell Adhesion/drug effects ; Cell Culture Techniques/*methods ; Cell Death/drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Implants, Experimental ; Kinetics ; Lactic Acid/*pharmacology ; Microscopy, Electron, Scanning ; *Microspheres ; Myocytes, Smooth Muscle/*cytology/drug effects ; Particle Size ; Phase Transition/*drug effects ; Polyglycolic Acid/*pharmacology ; Polylactic Acid-Polyglycolic Acid Copolymer ; Sus scrofa ; *Temperature ; }, abstract = {Microcarriers are widely used for the expansion of cells in vitro, but also offer an approach for combining cell transplantation and tissue bulking for regenerative medicine in a minimally invasive manner. This could be beneficial in conditions associated with muscle damage or atrophy, such as faecal incontinence, where the use of bulking materials or cell transplantation alone has proven to be ineffective. Microcarriers currently available have not been designed for this purpose and are likely to be suboptimal due to their physical and biochemical properties. The aim of this study was to investigate macroporous microspheres of polylactide-co-glycolide (PLGA), prepared using a thermally induced phase separation technique, for their suitability as cell microcarriers for the transplantation of smooth muscle cells. Cell attachment, growth and migration were studied and compared with commercially available porcine gelatin microcarriers (Cultispher-S) in suspension culture. Smooth muscle cells attached more rapidly to the PLGA microcarriers, which also significantly enhanced the rate of cell growth compared with Cultispher-S microcarriers. The majority of smooth muscle cells attached to the PLGA microcarriers in suspension culture were able to migrate away over a 15 day period of static culture, unlike Cultispher-S microcarriers which retained the majority of cells. The ability of PLGA microcarriers to enhance cell growth combined with their capacity to release cells at the sites of delivery are features that make them ideally suited for use as a cell transplantation delivery device in tissue engineering and regenerative medicine.}, }
@article {pmid21167429, year = {2010}, author = {Selves, J and Kamar, N and Mansuy, JM and Péron, JM}, title = {[Hepatitis E virus: A new entity].}, journal = {Annales de pathologie}, volume = {30}, number = {6}, pages = {432-438}, doi = {10.1016/j.annpat.2010.10.003}, pmid = {21167429}, issn = {0242-6498}, mesh = {Antibodies, Viral/blood ; Cholangitis/pathology/virology ; Communicable Diseases, Emerging/epidemiology/*virology ; Developing Countries ; Endemic Diseases ; Feces/microbiology ; France/epidemiology ; Genotype ; Hepatitis E/complications/diagnosis/epidemiology/pathology/physiopathology/transmission/*virology ; Hepatitis E virus/genetics/immunology/*isolation &amp; purification ; Hepatitis, Chronic/complications/pathology/virology ; Humans ; Immunocompetence ; Immunocompromised Host ; Liver Cirrhosis/etiology ; Liver Transplantation ; Postoperative Complications/pathology/virology ; Species Specificity ; Water Pollution ; }, abstract = {Hepatitis E virus (HEV) is a RNA enterically transmitted virus that causes large waterborne epidemics of acute hepatitis E in endemic regions (Asia and Africa). Sporadic hepatitis E is an emerging disease in developed countries such as France. The majority of acute hepatitis E in France is indigenous (non travel-associated) and is due to infection with HEV genotype 3. Diagnosis is made on the presence of specific serum antibodies and on viral RNA detection in serum or stools. Characteristic pathological signs of acute hepatitis E are severe intralobular necrosis, polymorph inflammation and acute cholangitis in portal tract with numerous neutrophils. Severe forms of hepatitis are associated with underlying chronic liver disease such alcoholic disease. In immunocompetent patients, HEV causes acute resolutive hepatitis and there is no chronic evolution. Conversely, chronic hepatitis E is frequent in immunocompromised patients with a risk of rapid evolution to cirrhosis. Histologic lesions of chronic hepatitis E are similar to those observed in patients chronically infected with hepatitis C virus with dense lymphocytic portal infiltrate, constant peacemeal necrosis and fibrosis.}, }
@article {pmid21162633, year = {2011}, author = {Goel, A and Aggarwal, R}, title = {Prevention of hepatitis E: another step forward.}, journal = {Future microbiology}, volume = {6}, number = {1}, pages = {23-27}, doi = {10.2217/fmb.10.151}, pmid = {21162633}, issn = {1746-0921}, abstract = {Hepatitis E virus (HEV) is frequently implicated in cases with acute viral hepatitis, particularly in developing countries. The infection, transmitted mainly by the fecal-oral route, is generally self-limited. A few affected individuals develop fulminant hepatic failure, a serious condition that is frequently fatal without liver transplantation. This outcome is particularly common when the infection occurs in pregnant women. A vaccine that contains a recombinant truncated capsid protein of HEV produced in an insect cell system has already been shown to be effective in preventing hepatitis E, at least in young men. However, it is not yet available on the market. In the evaluated article, Zhu et al. report the results of a large field trial of another vaccine against hepatitis E that contains a shorter part of the viral capsid protein, produced in Escherichia coli and adsorbed on alum. This trial, which included a large number of subjects of either gender aged 18-65 years, found this newer vaccine as safe and highly effective in preventing clinical disease caused by infection with HEV belonging to the genotype from which the vaccine was derived as well as another genotype. This study should prove to be a major stepping stone in our fight against this important disease pathogen.}, }
@article {pmid21150894, year = {2011}, author = {Khoruts, A and Sadowsky, MJ}, title = {Therapeutic transplantation of the distal gut microbiota.}, journal = {Mucosal immunology}, volume = {4}, number = {1}, pages = {4-7}, doi = {10.1038/mi.2010.79}, pmid = {21150894}, issn = {1935-3456}, mesh = {Anti-Bacterial Agents/adverse effects ; Biomass ; *Clostridioides difficile ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Humans ; Intestine, Large/*microbiology ; Metagenome ; }, abstract = {Although it is generally accepted that the distal gut microbiota are relatively stable in healthy adult individuals, a collapse of the microbial community structure resulting from antibiotic therapy or pathogen presence can lead to gut dysfunction. However, recent findings demonstrate that it is possible to engraft new microbiota from a donor source, resulting in the restoration of gut functionality and improvement in health. This builds upon decades of case reports and series in which fecal transfers were used to successfully treat refractory and recurrent Clostridium difficile infection. As fecal transplantation becomes part of mainstream medicine, it will likely provide a unique opportunity to study the interactions of humans with their attendant microbiota and allow greater insights into their synergistic functionality.}, }
@article {pmid21134376, year = {2011}, author = {Nijstad, N and Gautier, T and Briand, F and Rader, DJ and Tietge, UJ}, title = {Biliary sterol secretion is required for functional in vivo reverse cholesterol transport in mice.}, journal = {Gastroenterology}, volume = {140}, number = {3}, pages = {1043-1051}, doi = {10.1053/j.gastro.2010.11.055}, pmid = {21134376}, issn = {1528-0012}, mesh = {ATP Binding Cassette Transporter, Subfamily B/deficiency/genetics/*metabolism ; Animals ; Bile/*metabolism ; Bile Acids and Salts/metabolism ; Biological Transport ; Cholesterol/*metabolism ; Cholesterol Esters/metabolism ; Common Bile Duct/*metabolism/surgery ; Feces/chemistry ; Foam Cells/*metabolism/transplantation ; Hydrocarbons, Fluorinated/pharmacology ; Intestinal Mucosa/metabolism ; Kinetics ; Ligation ; Lipoproteins, HDL/metabolism ; Liver X Receptors ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Orphan Nuclear Receptors/agonists/metabolism ; Sulfonamides/pharmacology ; ATP-Binding Cassette Sub-Family B Member 4 ; }, abstract = {BACKGROUND &amp; AIMS: High-density lipoproteins (HDLs) protect against atherosclerotic cardiovascular disease, mainly by promoting reverse cholesterol transport (RCT). Biliary sterol secretion supposedly represents the final step in RCT, but the relevance of this pathway has not been explored. We tested the dependency of RCT on functional biliary sterol secretion.<br><br>METHODS: Macrophage-to-feces RCT was studied in mice with abolished (bile duct ligation) or decreased biliary sterol secretion (adenosine triphosphate binding cassette transporter B4 (Abcb4)-/- mice, with and without administration of a liver X receptor [LXR] agonist) after intraperitoneal injection of (3)H-cholesterol-loaded primary macrophage foam cells from mice. Fecal tracer excretion and also fecal mass sterol excretion were measured. Metabolism and tissue uptake of HDL cholesteryl ester was assessed with HDL kinetic studies.<br><br>RESULTS: Bile-duct ligation completely abolished RCT from (3)H-cholesterol-loaded macrophages to feces (P < .001). In Abcb4-/- mice lacking biliary cholesterol secretion, RCT was decreased markedly; fecal (3)H-tracer excretion was almost absent within neutral sterols (P < .001) and reduced within bile acids (P < .05). LXR activation stimulated RCT in wild-type (5.5-fold; P < .001) but not Abcb4-/- mice, whereas mass fecal sterol excretion increased similarly in both models (P < .05). Kinetic studies revealed minimal uptake of HDL cholesteryl ester by the intestine, which decreased on LXR activation (P < .05).<br><br>CONCLUSIONS: Functional RCT depends on biliary sterol secretion; there is no compensatory increase in RCT via bile acids. The stimulating effect of LXR agonists on RCT requires biliary cholesterol secretion. These results have implications for therapies against atherosclerotic cardiovascular disease targeting the RCT pathway.}, }
@article {pmid21119560, year = {2011}, author = {Briasoulis, A and Psevdos, G}, title = {Prompt diagnosis and treatment of strongyloidiasis in a renal transplant patient.}, journal = {Southern medical journal}, volume = {104}, number = {1}, pages = {72-73}, doi = {10.1097/SMJ.0b013e3181f61647}, pmid = {21119560}, issn = {1541-8243}, mesh = {Adult ; Animals ; Antiparasitic Agents/*administration &amp; dosage ; Diagnosis, Differential ; *Early Diagnosis ; Feces/parasitology ; Female ; Humans ; Ivermectin/*administration &amp; dosage ; Kidney Failure, Chronic/surgery ; *Kidney Transplantation ; Strongyloides stercoralis/isolation &amp; purification ; Strongyloidiasis/*diagnosis/*drug therapy/parasitology ; Tomography, X-Ray Computed ; }, }
@article {pmid22347265, year = {2010}, author = {Dehkordy, AB and Rafiei, A and Alavi, S and Latifi, S}, title = {Prevalence of cryptosporidium infection in immunocompromised patients, in South-west of iran, 2009-10.}, journal = {Iranian journal of parasitology}, volume = {5}, number = {4}, pages = {42-47}, pmid = {22347265}, issn = {2008-238X}, abstract = {BACKGROUND: Cryptosporidium is a protozoan parasite with worldwide distribution. The aim of this study was to estimate the prevalence of Cryptosporidium infection by antigen detection in faeces among immunocompromised patients referred to educational hospitals of Ahvaz City, South-West of Iran, 2009-2010.<br><br>METHODS: Fecal samples from 176 immunocompromised patients were collected and Cryptosporidium coproantigen test was performed using ELISA method (DRG kit, Germany). A questionnaire was completed for each case and the results were analyzed using descriptive and Chi-Square tests, by SPSS statistical software (15(th) version).<br><br>RESULTS: Our study indicated 5.1% Cryptosporidium infection prevalence in the immunocompromised participated population. Furthermore, 4.2 %, 4 %, 4.5 % and 9.1 % infection rates were identified in children suffered from hematopoietic malignancy, adult cancer patients, renal transplant recipients, and HIV(+) cases, respectively. There was not significant correlation between the infection and age and gender (P>0.05). Infection was most frequent among HIV(+) patients.<br><br>CONCLUSION: The present study confirmed the high prevalence of Cryptosporidium antigen in fecal samples of immunocompromised patients in the region. As no chemotherapeutic agents have yet proven, especially in immunosuppressed patients, therefore our results highlight the importance of preventive intervention in these groups.}, }
@article {pmid21117256, year = {2010}, author = {Zhu, ZJ and Shen, ZY and Gao, W and Zheng, H and Deng, YL and Pan, C and Sun, LY and Zeng, ZG and Sun, JS}, title = {Feasibility of using a liver infected with Clonorchis sinensis for liver transplantation: fourteen cases.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {16}, number = {12}, pages = {1440-1442}, doi = {10.1002/lt.22147}, pmid = {21117256}, issn = {1527-6473}, mesh = {Adult ; Animals ; Anthelmintics/therapeutic use ; Clonorchiasis/complications/drug therapy ; Clonorchis sinensis/*isolation &amp; purification ; Feasibility Studies ; Female ; Follow-Up Studies ; Graft Rejection/epidemiology ; Humans ; Liver/*parasitology ; Liver Diseases/*surgery ; Liver Transplantation/*mortality ; Male ; Middle Aged ; Praziquantel/therapeutic use ; Risk Factors ; Survival Rate ; Treatment Outcome ; }, abstract = {Use of livers infected with Clonorchis sinensis as donor organs for transplantation is controversial because of the potential associated risks. The low availability of donor livers at Tianjin First Center Hospital since 2003 prompted us to undertake cadaveric liver transplantation in 14 patients using donor livers infected with C. sinensis. None of the donors had been diagnosed with liver fluke infection before organ procurement, and in none of them was there laboratory evidence of abnormal liver function. After livers had been harvested and preserved, dead liver flukes were found in the bile of each donor; subsequent pathological examination of the flukes confirmed the diagnosis of clonorchiasis. Conventional orthotopic liver transplantation, with insertion of a T- tube, was undertaken in all 14 patients. Praziquantel, 25 mg/kg three times daily for two days, was administrated to the recipients starting on postoperative day 2. Results of tests of liver function improved rapidly after the operation in all of the patients. The median duration of follow-up was 31 months. The 1- and 3-year survival rates of the grafts were 85.7% and 78.6%, respectively. Postoperative biliary complications occurred in 2 patients (14.3%). No ova were detected in the bile or feces of any of the patients postoperatively. These findings suggest that livers infested with C. sinensis can be used as donor organs for liver transplantation. Further studies are required to establish definitive criteria for determining whether such donor organs may be used in a liver transplantation program.}, }
@article {pmid21052757, year = {2011}, author = {Arnan, M and Gudiol, C and Calatayud, L and Liñares, J and Dominguez, M&#xc1; and Batlle, M and Ribera, JM and Carratalà, J and Gudiol, F}, title = {Risk factors for, and clinical relevance of, faecal extended-spectrum β-lactamase producing Escherichia coli (ESBL-EC) carriage in neutropenic patients with haematological malignancies.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {30}, number = {3}, pages = {355-360}, pmid = {21052757}, issn = {1435-4373}, mesh = {Bacteremia/complications/microbiology ; Carrier State/*microbiology ; Cohort Studies ; Drug Resistance, Bacterial ; Escherichia coli/classification/*drug effects/enzymology/*isolation &amp; purification ; Escherichia coli Infections/complications/*microbiology ; Feces/*microbiology ; Female ; Hematologic Neoplasms/complications/*microbiology ; Humans ; Leukemia/complications/microbiology ; Male ; Middle Aged ; Molecular Typing ; Neutropenia/complications ; Risk Factors ; beta-Lactamases/genetics/*metabolism ; }, abstract = {The purpose of this study was to assess the risk factors for, and the clinical relevance of, faecal carriage by extended-spectrum β-lactamase producing Escherichia coli (ESBL-EC) in neutropenic cancer patients (NCP). An observational prospective multicentre cohort study was conducted over 2 years at two teaching hospitals. Patients with acute leukaemia or undergoing stem cell transplantation were included during neutropenia episodes. Rectal swabs were obtained at hospital admission and weekly thereafter until discharge or death. ESBL-EC colonized episodes were compared with non-colonized episodes. ESBL-EC strains were studied by PCR and isoelectric focusing, and molecular typing was performed by pulsed field gel electrophoresis (PFGE). Among 217 episodes of neutropenia, the prevalence of ESBL-EC faecal carriage was 29% (14% at hospital admission). Multivariate analysis identified previous antibiotics as the only independent risk factor for ESBL-EC faecal colonization (OR 5.38; 95% CI 2.79-10.39). Analysis of ESBL-EC isolates revealed a polyclonal distribution with CTX-M predominance (81.3%). E. coli bacteraemia was mainly caused by non-ESBL producing strains and its rate was similar in both groups (13% vs. 11%). We found no association between ESBL-EC carriage and an increased risk of ESBL-EC bacteremia or a negative influence on other clinical outcomes, including length of hospitalisation, early and overall mortality rates. ESBL-EC faecal colonization is frequent in NCP but difficult to identify by epidemiological or clinical features on presentation. Prior antibiotic therapy is the major associated risk factor. In this setting colonization does not appear to have a significant clinical relevance. Thus, routine testing for ESBL-EC faecal carriage does not seem to be beneficial.}, }
@article {pmid21046117, year = {2011}, author = {Miyasaka, EA and Raghavan, S and Gilmont, RR and Mittal, K and Somara, S and Bitar, KN and Teitelbaum, DH}, title = {In vivo growth of a bioengineered internal anal sphincter: comparison of growth factors for optimization of growth and survival.}, journal = {Pediatric surgery international}, volume = {27}, number = {2}, pages = {137-143}, pmid = {21046117}, issn = {1437-9813}, support = {R01 DK071614/DK/NIDDK NIH HHS/United States ; T32 HD007505/HD/NICHD NIH HHS/United States ; T32HD007505/HD/NICHD NIH HHS/United States ; DK071614/DK/NIDDK NIH HHS/United States ; R01 DK071614-04/DK/NIDDK NIH HHS/United States ; 1RC1DK08715/DK/NIDDK NIH HHS/United States ; RC1 DK087151/DK/NIDDK NIH HHS/United States ; }, mesh = {Anal Canal/*growth &amp; development/transplantation ; Animals ; Bioengineering/*methods ; Disease Models, Animal ; Fecal Incontinence/drug therapy/*surgery ; Fibroblast Growth Factor 2/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Smooth/drug effects/growth &amp; development ; Platelet-Derived Growth Factor/*pharmacology ; Tissue Engineering/methods ; Vascular Endothelial Growth Factor A/*pharmacology ; }, abstract = {PURPOSE: Our laboratory has developed and implanted a novel bioengineered internal anal sphincter (IAS) to treat anal incontinence. Fibroblast growth factor-2 (FGF-2) has been used in mice; however, the optimal growth factor for successful IAS implantation is unclear. This study compares several growth factors in order to optimize IAS viability and functionality.<br><br>METHODS: Bioengineered IAS rings were implanted subcutaneously into the dorsum of wildtype C57Bl/6 mice, with an osmotic pump dispensing FGF-2, vascular endothelial growth factor (VEGF), or platelet-derived growth factor (PDGF) (n&#xa0;=&#xa0;4 per group). Control mice received IAS implants but no growth factor. The IAS was harvested approximately 25&#xa0;days post-implantation. Tissue was subjected to physiologic testing, then histologically analyzed. Muscle phenotype was confirmed by immunofluorescence.<br><br>RESULTS: All implants supplemented with growth factors maintained smooth muscle phenotype. Histological scores, blood vessel density and muscle fiber thickness were all markedly better with growth factors. Neovascularization was comparable between the three growth factors. Basal tonic force of the constructs was highest with VEGF or PDGF.<br><br>CONCLUSION: All growth factors demonstrated excellent performance. As our ultimate goal is clinical implantation, our strong results with PDGF, a drug approved for use in the United States and the European Union, pave the way for translating bioengineered IAS implantation to the clinical realm.}, }
@article {pmid21045476, year = {2010}, author = {Oberoi, A and Varghese, SR and John, MJ}, title = {Strongyloides stercoralis infection in a patient undergoing allogeneic stem cell transplantation.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {53}, number = {4}, pages = {895-896}, doi = {10.4103/0377-4929.72050}, pmid = {21045476}, issn = {0974-5130}, mesh = {Adult ; Animals ; Feces/parasitology ; Humans ; *Immunocompromised Host ; Larva ; Male ; Microscopy ; Stem Cell Transplantation/*adverse effects ; Strongyloides stercoralis/*isolation &amp; purification ; Strongyloidiasis/*diagnosis ; }, }
@article {pmid20952036, year = {2010}, author = {Vanni, AJ and Buckley, JC and Zinman, LN}, title = {Management of surgical and radiation induced rectourethral fistulas with an interposition muscle flap and selective buccal mucosal onlay graft.}, journal = {The Journal of urology}, volume = {184}, number = {6}, pages = {2400-2404}, doi = {10.1016/j.juro.2010.08.004}, pmid = {20952036}, issn = {1527-3792}, mesh = {Humans ; Mouth Mucosa/*transplantation ; Postoperative Complications/etiology/*surgery ; Radiation Injuries/complications/*surgery ; Rectal Fistula/etiology/*surgery ; Retrospective Studies ; *Surgical Flaps ; Urethral Diseases/etiology/*surgery ; Urinary Fistula/etiology/*surgery ; }, abstract = {PURPOSE: Rectourethral fistulas are a rare but devastating complication of pelvic surgery and radiation. We review, analyze and describe the management and outcomes of nonradiated and radiation/ablation induced rectourethral fistulas during a consecutive 12-year period.<br><br>MATERIALS AND METHODS: We performed a retrospective review of patients undergoing rectourethral fistula repair between January 1, 1998 and December 31, 2009. Patient demographics as well as preoperative, operative and postoperative data were obtained. All rectourethral fistulas were repaired using an anterior transperineal approach with a muscle interposition flap and selective use of a buccal mucosal graft urethral patch onlay.<br><br>RESULTS: A total of 74 patients with rectourethral fistulas underwent repair with an anterior perineal approach and muscle interposition flap (68 gracilis muscle interposition flaps, 6 other muscle interposition flaps). We compared 35 nonradiated and 39 radiated/ablation induced rectourethral fistulas. Concurrent urethral strictures were present in 11% of nonradiated and 28% of radiated/ablation rectourethral fistulas. At a mean followup of 20 months 100% of nonradiated rectourethral fistulas were closed with 1 procedure while 84% of radiated/ablation rectourethral fistulas were closed in a single stage. Of the patients with nonradiated rectourethral fistulas 97% had the bowel undiverted. Of those undiverted cases 100% were without bowel complication. Of the patients with radiated/ablation rectourethral fistulas 31% required permanent fecal diversion.<br><br>CONCLUSIONS: Successful rectourethral fistula closure can be achieved for nonradiated (100%) and radiation/ablation (84%) rectourethral fistulas using a standard anterior perineal approach with an interposition muscle flap and selective use of buccal mucosal graft, providing a standard for rectourethral fistula repair. Even the most complex radiation/ablation rectourethral fistula can be repaired avoiding permanent urinary and fecal diversion.}, }
@article {pmid20940607, year = {2010}, author = {Hancke, E and Rikas, E and Suchan, K and Völke, K}, title = {Dermal flap coverage for chronic anal fissure: lower incidence of anal incontinence compared to lateral internal sphincterotomy after long-term follow-up.}, journal = {Diseases of the colon and rectum}, volume = {53}, number = {11}, pages = {1563-1568}, doi = {10.1007/DCR.0b013e3181f0869f}, pmid = {20940607}, issn = {1530-0358}, mesh = {Adult ; Aged ; Aged, 80 and over ; Chronic Disease ; Digestive System Surgical Procedures/*methods ; Fecal Incontinence/epidemiology ; Female ; Fissure in Ano/*surgery ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Postoperative Complications/epidemiology ; Skin Transplantation ; Statistics, Nonparametric ; *Surgical Flaps ; Surveys and Questionnaires ; Treatment Outcome ; }, abstract = {PURPOSE: Internal sphincterotomy is considered the standard for treating anal fissure, but it is associated with a risk of impaired anal continence. This study aimed to conduct a long-term follow-up to compare postoperative anal continence using dermal flap coverage or lateral internal sphincterotomy for treatment of chronic anal fissure.<br><br>PATIENTS AND METHODS: Sixty patients with chronic anal fissure (male/female, 30:30; age range, 22-79 y) were treated by open lateral internal sphincterotomy (n = 30) or dermal flap coverage (n = 30) from 1997 to 2002. The postoperative course was evaluated using the clinical charts. A standardized questionnaire assessing complaints and anal continence was sent to the patients 70 to 94 months postoperatively and phone interviews were conducted.<br><br>RESULTS: Operations were performed with general anesthesia as short-stay hospital procedures. The chronic fissure wounds healed in both groups regardless of surgical technique. Symptoms of mild anal incontinence (ie, soiling, flatus) were present 3 months after operation in 6 of 30 (20.0%) patients with lateral internal sphincterotomy and in no patient with dermal flap coverage (P < .05); 70 to 94 months postoperatively, mild anal incontinence was present in 10 of 21 (47.6%) patients with lateral internal sphincterotomy and in 1 of 17 (5.8%) patients with dermal flap coverage (P < .05).<br><br>CONCLUSION: Long-term follow-up shows a very low incidence of mild anal incontinence after dermal flap coverage. We conclude from this study that the dermal flap procedure appears to be efficacious without an increased risk of incontinence and with results comparable to lateral internal sphincterotomy. The dermal flap procedure can be recommended for patients following failed conservative fissure treatment without the potential risk of anal incontinence.}, }
@article {pmid20920725, year = {2010}, author = {Danielson, J and Karlbom, U and Graf, W and Wester, T}, title = {Long-term outcome after free autogenous muscle transplantation for anal incontinence in children with anorectal malformations.}, journal = {Journal of pediatric surgery}, volume = {45}, number = {10}, pages = {2036-2040}, doi = {10.1016/j.jpedsurg.2010.06.009}, pmid = {20920725}, issn = {1531-5037}, mesh = {Adolescent ; Adult ; Anal Canal/abnormalities/surgery ; Anorectal Malformations ; Anus, Imperforate/psychology/surgery ; Attitude to Health ; Child ; Defecation/physiology ; Fecal Incontinence/*surgery ; Female ; Flatulence ; Follow-Up Studies ; Health Status ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; *Outcome Assessment, Health Care ; Quality of Life ; Rectum/abnormalities/physiology/surgery ; Surveys and Questionnaires ; Transplantation, Autologous/*methods ; }, abstract = {PURPOSE: Patients with high anorectal anomalies are often incontinent after reconstruction, particularly with the older forms of surgical treatment, that is, anorectal pull-through or Stephen's operations. In 1974, a new treatment for anal incontinence in children was introduced at the Akademiska Hospital: free autogenous muscle transplantation (FAMT) to the perirectal area. All the patients receiving FAMT were totally incontinent before the procedure and had no rectal sensitivity. The aim of this study was to evaluate the long-term functional outcome of this procedure.<br><br>METHODS: Twenty-two patients (17 males) operated on with FAMT below the age of 15 years were identified through records. One of the patients had died, and 2 were not available for follow-up. The remaining 19 were sent a validated bowel function questionnaire, and 15 (78.9%) of 19 patients responded (12 males). These 15 patients were compared with 15 patients with the same sex, age, and a similar malformation from our patient database.<br><br>RESULTS: At follow-up, after an average of 30 years postoperatively, 2 of 15 patients with FAMT had a stoma compared with 3 of 15 in the control group. The Miller incontinence score had a mean of 6.2 (median, 6; range, 0-15) in the FAMT group and 3.7 (median, 4; range, 0-12) in the control group. All patients in both groups could sense stool, and 11 of 13 patients in the FAMT group could distinguish between feces and flatus.<br><br>CONCLUSIONS: The patients with FAMT had a slightly inferior anorectal function compared with the controls. Considering they were all totally incontinent before FAMT, we conclude that FAMT has an acceptable effect 30 years postoperatively. Therefore, we find that FAMT could be an alternative for anorectal malformation patients who are totally incontinent.}, }
@article {pmid20888858, year = {2011}, author = {Giordano, MO and Martinez, LC and Masachessi, G and Barril, PA and Ferreyra, LJ and Isa, MB and Valle, MC and Massari, PU and Nates, SV}, title = {Evidence of closely related picobirnavirus strains circulating in humans and pigs in Argentina.}, journal = {The Journal of infection}, volume = {62}, number = {1}, pages = {45-51}, doi = {10.1016/j.jinf.2010.09.031}, pmid = {20888858}, issn = {1532-2742}, mesh = {Animals ; Argentina/epidemiology ; Base Sequence ; Diarrhea/virology ; Host Specificity/genetics ; Humans ; Molecular Sequence Data ; Nucleotide Mapping ; Phylogeny ; Picobirnavirus/*classification/*genetics/isolation &amp; purification ; RNA Virus Infections/*epidemiology/*virology ; RNA-Dependent RNA Polymerase/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, RNA ; Swine ; }, abstract = {BACKGROUND: On the basis of the published literature, it is still difficult to draw conclusions as to whether picobirnavirus (PBV) circulation is influenced by host species restriction.<br><br>OBJECTIVE: To provide data regarding the genetic relatedness between porcine and human PBV strains present in Argentina as a means of defining the host range and epidemiology of these viruses.<br><br>METHODS: Fecal specimens (n&#xa0;=&#xa0;74) collected from kidney transplant patients (n&#xa0;=&#xa0;55) and piglets (n&#xa0;=&#xa0;19) were analyzed by RT-PCR using primers designed to amplify the porcine PBV genomic segment 2. Amplified sequences were further examined phylogenetically.<br><br>RESULTS: By RT-PCR amplification 14 of 74 samples rendered amplicons of the expected 282 base pair size (8 detected from humans and 6 from pigs). Eleven amplicons (5 from humans and 6 from pigs) were selected for sequencing and subjected to phylogenetic analysis. The eleven amplicons revealed similarities between human and porcine viral sequences that ranged between 94.7 and 100% in identity. Phylogenetic analysis identified these 11 strains as PBV genogroup I-related strains and showed that they grouped as a single separate clade distinct from other PBV strains detected in humans and porcine from other countries.<br><br>CONCLUSIONS: The present study suggests that closely related PBV strains infect both pigs and humans in Argentina and that the epidemiology of PBVs is not species restricted.}, }
@article {pmid20848295, year = {2010}, author = {Bil-Lula, I and Ussowicz, M and Rybka, B and Wendycz-Domalewska, D and Ryczan, R and Gorczyńska, E and Kałwak, K and Woźniak, M}, title = {PCR diagnostics and monitoring of adenoviral infections in hematopoietic stem cell transplantation recipients.}, journal = {Archives of virology}, volume = {155}, number = {12}, pages = {2007-2015}, pmid = {20848295}, issn = {1432-8798}, mesh = {Adenoviridae Infections/*diagnosis/*epidemiology/mortality/virology ; Adenoviruses, Human/*isolation &amp; purification ; Adolescent ; Adult ; Blood/virology ; Child ; Child, Preschool ; Feces/virology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Infant ; Male ; Polymerase Chain Reaction/methods ; Prevalence ; Retrospective Studies ; Risk Factors ; Urine/virology ; Virology/methods ; }, abstract = {After stem cell transplantation, human patients are prone to life-threatening opportunistic infections with a plethora of microorganisms. We report a retrospective study on 116 patients (98 children, 18 adults) who were transplanted in a pediatric bone marrow transplantation unit. Blood, urine and stool samples were collected and monitored for adenovirus (AdV) DNA using polymerase chain reaction (PCR) and real-time PCR (RT-PCR) on a regular basis. AdV DNA was detected in 52 (44.8%) patients, with mortality reaching 19% in this subgroup. Variables associated with adenovirus infection were transplantations from matched unrelated donors and older age of the recipient. An increased seasonal occurrence of adenoviral infections was observed in autumn and winter. Analysis of immune reconstitution showed a higher incidence of AdV infections during periods of low T-lymphocyte count. This study also showed a strong interaction between co-infections of AdV and BK polyomavirus in patients undergoing hematopoietic stem cell transplantations.}, }
@article {pmid20847624, year = {2010}, author = {Kajbafzadeh, AM and Elmi, A and Talab, SS and Esfahani, SA and Tourchi, A}, title = {Functional external anal sphincter reconstruction for treatment of anal incontinence using muscle progenitor cell auto grafting.}, journal = {Diseases of the colon and rectum}, volume = {53}, number = {10}, pages = {1415-1421}, doi = {10.1007/DCR.0b013e3181e53088}, pmid = {20847624}, issn = {1530-0358}, mesh = {Anal Canal/pathology/physiopathology/*surgery ; Animals ; Disease Models, Animal ; Electromyography ; Feasibility Studies ; Fecal Incontinence/pathology/physiopathology/*surgery ; Guided Tissue Regeneration/*methods ; Male ; Manometry ; Muscle, Skeletal/*pathology/physiopathology ; Rabbits ; *Stem Cell Transplantation ; }, abstract = {PURPOSE: This study aimed to investigate the feasibility of autologous muscle progenitor cell transplantation for anal sphincter regeneration in a rabbit model of anal incontinence. We examined the serial changes in structure, with particular emphasis on histology and functional properties of the anal sphincter.<br><br>METHODS: External anal sphincterotomy was performed in 21 rabbits; these rabbits were randomly assigned to 2 groups. In group I (n = 9), autologous muscle progenitor cells were isolated from quadriceps myofiber explants, labeled with PKH-26, and injected into sphincter 3 weeks after sphincterotomy. In group II (n = 12), saline buffer was injected at the site of damage. Sphincter electromyography and manometry were performed immediately before sphincterotomy and 14, 28, and 60 days after injection in 3 animals in each group at every interval and the findings were correlated with histomorphological studies. In addition, electromyography and manometry were performed in the remaining 3 rabbits in group II after 6 months.<br><br>RESULTS: In group II, a flaccid sphincter persisted during the 6 months of follow-up. In group I, muscle progenitor autografting accelerated sphincter myofiber repair and improvement in functional capacity of the damaged sphincter. Fluorescently labeled cells were detected in all of the grafted sphincters; regenerated myotubes were detectable at the injection site as evidenced by the presence of desmin. We also observed a significant decrease in interstitial fibrosis in the 4th week and strikingly higher amounts of Ki-67-positive cells in group I. Manometry and electromyography showed a significant improvement in the mean resting anal canal pressure and sphincteric electrical activity 4 weeks after cell injection, respectively.<br><br>CONCLUSION: Transplanting muscle progenitor cells showed the potential for recapitulation of a myogenic program when injected into deficient rabbit anal sphincter. Objective anal measures of resting and stimulated pressures and electromyographic profile improved. Stem cell-mediated anal myoplasty warrants additional investigation as a new method to treat anal incontinence before attempting this modality in the clinical setting.}, }
@article {pmid20740157, year = {2010}, author = {Rossetto, A and Cerato, F and Cedolini, C and Arena, MC and Bresadola, V and Terrosu, G}, title = {Post-Traumatic Right Lumbar Abscess as First Manifestation of Perforated Right Colon Cancer - A Case Report.}, journal = {Case reports in oncology}, volume = {3}, number = {1}, pages = {40-44}, pmid = {20740157}, issn = {1662-6575}, abstract = {Besides most common signs and symptoms suggesting a colic cancer, sometimes the clinical presentation can be difficult. Extra-abdominal abscess as a first sign of perforated colon carcinoma is a very unusual finding. We report a case of an old male patient, in bad general condition, with a post-traumatic finding of right lumbar abscess. After the percutaneous drainage with discharge of fecal material and a postponed explorative laparotomy, we discovered a perforated right colon carcinoma with a covered perforation affecting the duodenum wall and spreading to the hepatic bedand over to the back lumbar muscular wall. Because of the diffusion of the tumor, the patient was treated with palliative surgery with duodenum suture, right colon segment resection and subsequent ileocolic anastomosis with an uneventful postoperative course. The patient died 2 months later because of neoplastic cachexia.}, }
@article {pmid20733481, year = {2010}, author = {Montes, M and Sawhney, C and Barros, N}, title = {Strongyloides stercoralis: there but not seen.}, journal = {Current opinion in infectious diseases}, volume = {23}, number = {5}, pages = {500-504}, pmid = {20733481}, issn = {1473-6527}, support = {R01 TW007642/TW/FIC NIH HHS/United States ; R01 TW007642-04/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Helminth/blood ; Clinical Laboratory Techniques/*methods ; DNA, Helminth/genetics/isolation &amp; purification ; Feces/parasitology ; Humans ; Immunoprecipitation ; Parasitology/*methods ; Polymerase Chain Reaction/methods ; Sensitivity and Specificity ; Strongyloides stercoralis/*isolation &amp; purification ; Strongyloidiasis/*diagnosis/parasitology ; }, abstract = {PURPOSE OF REVIEW: Diagnosis of Strongyloides stercoralis is often delayed owing to patients presenting with nonspecific gastrointestinal complaints, a low parasite load and irregular larval output. Although several diagnostic methods exist to detect the presence of S. stercoralis there is no gold standard. In immunocompromised hosts (patients with malignancy, organ transplantation or concurrent human T-cell-lymphocytic virus 1 infection or those on corticosteroid therapy), autoinfection can go unchecked with large numbers of invasive Strongyloides larvae disseminating widely and causing hyperinfection with dissemination, which can be fatal. This review will highlight current published research on improved diagnostic methods for S. stercoralis and the immune mechanisms thought to be responsible for hyperinfection syndrome.<br><br>RECENT FINDINGS: Recent advances in diagnosis of S. stercoralis include a luciferase immunoprecipitation system that shows increased sensitivity and specificity to detect S. stercoralis-specific antibodies and a real-time quantitative PCR method to detect S. stercoralis in fecal samples. The severe clinical manifestations of S. stercoralis observed in human T-cell-lymphocytic virus 1 coinfected patients has been associated with an increased proportion of regulatory T cells that may be responsible for blunting otherwise effective granulocyte responses.<br><br>SUMMARY: Strongyloidiasis is a major global health challenge that is underestimated in many countries. Novel diagnostic methods are expected to improve epidemiological studies and control efforts for prevention and treatment of strongyloidiasis. More studies are needed to unveil the mechanisms of severe clinical manifestations of human strongyloidiasis.}, }
@article {pmid20706005, year = {2010}, author = {Roslev, P and Bukh, AS and Iversen, L and Sønderbo, H and Iversen, N}, title = {Application of mussels as biosamplers for characterization of faecal pollution in coastal recreational waters.}, journal = {Water science and technology : a journal of the International Association on Water Pollution Research}, volume = {62}, number = {3}, pages = {586-593}, doi = {10.2166/wst.2010.910}, pmid = {20706005}, issn = {0273-1223}, mesh = {Agriculture ; Animals ; Bivalvia/*microbiology ; Denmark ; Environmental Monitoring/*methods ; Escherichia coli/genetics/isolation &amp; purification ; Genetic Markers ; Humans ; Phylogeny ; Recreation ; Sewage ; Time Factors ; Water Microbiology/*standards ; Water Pollutants/*analysis ; Water Pollution/*prevention &amp; control ; }, abstract = {Sources of faecal pollution in coastal recreational waters may be identified by analysing different host associated microorganisms or molecular markers. However, the microbial targets are often present at low numbers in moderately impacted waters, and often exhibit significant temporal and spatial variability in waters with fluctuating faecal loads. This patchy occurrence can limit successful detection of relevant targets in microbial source tracking studies. In this study, we explored the possibility for using the blue mussel (Mytilus edulis) as a biosampler for accumulation of faecal bacteria relevant for microbial source tracking. Non-contaminated blue mussels were transferred to three coastal recreational waters affected by faecal pollution of unknown origin. Molecular markers associated with animal and human waste were targeted by PCR and compared in seawater and mussel samples. The results demonstrated that transplanted mussels in simple enclosures accumulated and retained elevated levels of molecular markers associated with different types of faecal pollution. The targets included a novel putative human associated E. coli subgroup B2 VIII clone, and animal and human associated markers in enterococci (esp, M19, M66, M90, and M91). Human (sewage) associated markers including esp and M66 were sometimes not detectable in seawater samples despite known wastewater contamination, whereas the markers were detectable in mussels. We suggest that transplanted mussels should be considered as potential biosamplers in studies focusing on identifying source of faecal pollution in low or moderately impacted recreational waters. Bioaccumulation of molecular markers in mussels for several days may represent the water quality better than traditional grab samples from the water column.}, }
@article {pmid20687839, year = {2010}, author = {Tschudin Sutter, S and Frei, R and Dangel, M and Gratwohl, A and Bonten, M and Widmer, AF}, title = {Not all patients with vancomycin-resistant enterococci need to be isolated.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {51}, number = {6}, pages = {678-683}, doi = {10.1086/655824}, pmid = {20687839}, issn = {1537-6591}, mesh = {Bacteremia/epidemiology/microbiology/prevention &amp; control ; Bacterial Proteins/genetics ; Bone Marrow Transplantation/adverse effects ; Carbon-Oxygen Ligases/genetics ; Cross Infection/*epidemiology/microbiology/*prevention &amp; control ; DNA, Bacterial/genetics ; Enterococcus/*drug effects/genetics/isolation &amp; purification ; Feces/microbiology ; Female ; Gram-Positive Bacterial Infections/*epidemiology/microbiology/*prevention &amp; control ; Humans ; Immunocompromised Host ; Leukemia/complications/therapy ; Male ; Middle Aged ; *Patient Isolation ; Peptide Synthases/genetics ; Risk Factors ; *Vancomycin Resistance ; }, abstract = {BACKGROUND: Vancomycin-resistant enterococci (VRE) have triggered multiple outbreaks. However, VRE of genotype vanC appear not to be associated with outbreaks. The goal of this study was to estimate the risk of bloodstream infections in patients colonized with VRE of genotype vanC who received care from a bone marrow transplant unit for patients with leukemia, where only standard precautions were implemented for VRE of genotype vanC during the last 9 years.<br><br>METHODS: Since 2000, all patients in the bone marrow transplant unit underwent routine VRE rectal screening, data were prospectively entered in a database, and isolates were molecularly characterized. Infection control policy required contact isolation for patients infected with VRE of genotype vanA or vanB but only standard precautions for patients infected with VRE of genotype vanC.<br><br>RESULTS: From January 2000 to July 2008, 290 isolates of VRE of genotype vanC obtained from 273 different patients were identified, with an incidence of 25-43 isolates/year. Of 290 isolates, 285 (98%) were identified in rectal screening swabs, 5 were from other body sites, and none required specific treatment. During the entire study period, only 1 case of bloodstream infection was detected, reflecting an incidence of 1 (0.4%) of the 273 patients, or <0.2 cases per 1000 patient-days. No outbreaks were recorded.<br><br>CONCLUSIONS: These data provide strong evidence that carriers of VRE of genotype vanC do not require contact isolation, thereby saving resources and potentially improving patient care. The genotype should be routinely determined in areas with a high prevalence of VRE of genotype vanC.}, }
@article {pmid20678959, year = {2010}, author = {Tavitian, S and Péron, JM and Huynh, A and Mansuy, JM and Ysebaert, L and Huguet, F and Vinel, JP and Attal, M and Izopet, J and Récher, C}, title = {Hepatitis E virus excretion can be prolonged in patients with hematological malignancies.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {49}, number = {2}, pages = {141-144}, doi = {10.1016/j.jcv.2010.06.016}, pmid = {20678959}, issn = {1873-5967}, mesh = {Adult ; Aged ; Feces/virology ; Female ; France ; Genotype ; Hematologic Neoplasms/*complications/drug therapy ; Hepatitis Antibodies/blood ; Hepatitis E/*epidemiology/transmission/*virology ; Hepatitis E virus/*isolation &amp; purification ; Humans ; Immunocompromised Host ; Immunoglobulin G/blood ; Male ; Middle Aged ; Molecular Sequence Data ; Prevalence ; RNA, Viral/blood/genetics ; Sequence Analysis, DNA ; Time Factors ; Transaminases/blood ; *Virus Shedding ; }, abstract = {BACKGROUND: Hepatitis E virus (HEV) is transmitted via the fecal-oral route and locally acquired sporadic hepatitis E can occur in Western countries. Chronic hepatitis E virus infections have been recently described in solid organ transplant recipients. There is little data on the evolution of hepatitis E in patients immunocompromised for other reasons.<br><br>OBJECTIVES: The aim of this study was to evaluate the clinical course of hepatitis E in patients immunocompromised because of hematological malignancies.<br><br>STUDY DESIGN: Starting on November 2003, all patients in the Toulouse University Hospital Hematology Department with unexplained elevated transaminases were tested for hepatitis E using viral RNA detection in serum or stools and serology.<br><br>RESULTS: Acute hepatitis E was diagnosed in six middle-aged hematology patients. All cases were autochthonous. HEV strains were genotype 3. All patients had a significant increase of transaminases (6-95 upper limit normal) and only two had HEV IgG. Five patients were asymptomatic and one had jaundice. Transmission of HEV occurred between two patients who had overlapping stays in the hematology ward. All five evaluable patients ultimately cleared their HEV but viremia was prolonged over 6 months in three patients and specific treatment had to be postponed in two patients.<br><br>CONCLUSION: Screening for HEV should be carried out routinely in hematology patients with elevated transaminases, and patient-to-patient transmission is a concern. Further studies are required to determine whether management of malignancy, particularly stem-cell transplantation should be adapted to HEV status.}, }
@article {pmid20662620, year = {2010}, author = {Garborg, K and Waagsbø, B and Stallemo, A and Matre, J and Sundøy, A}, title = {Results of faecal donor instillation therapy for recurrent Clostridium difficile-associated diarrhoea.}, journal = {Scandinavian journal of infectious diseases}, volume = {42}, number = {11-12}, pages = {857-861}, doi = {10.3109/00365548.2010.499541}, pmid = {20662620}, issn = {1651-1980}, mesh = {Administration, Rectal ; Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {We report a success rate of 83% with faecal donor instillation therapy (FDIT) in this retrospective study of 40 patients with recurrent Clostridium difficile-associated diarrhoea (CDAD), treated at a medium sized Norwegian hospital from 1994 through 2008. The stool transplant was instilled either in the duodenum through a gastroscope or in the colon through a colonoscope with next of kin or other household member as donor. In 29 cases (73%) the first treatment was successful, with no documented recurrence of diarrhoeal disease within 80 days. Of the 11 patients failing to respond to the first instillation treatment, 6 patients received a second instillation, 4 of which were successful. A total of 33 patients (83%) were successfully treated with FDIT. Of the 7 non-responders, 5 were seriously ill due to long lasting diarrhoeal disease and co-morbidity and died within 80 days after the procedure, and 2 were believed to have inflammatory bowel disease with response to corticosteroid treatment. No adverse effects of FDIT were observed. In our experience the procedure is easy to perform, well tolerated, effective, and may be a valuable treatment option in selected cases.}, }
@article {pmid20635145, year = {2010}, author = {Lee, M and Shelton, AA and Concepcion, WL and Bonham, CA and Daugherty, TJ}, title = {Fulminant Clostridium difficile colitis in a post-liver transplant patient.}, journal = {Digestive diseases and sciences}, volume = {55}, number = {9}, pages = {2459-2462}, pmid = {20635145}, issn = {1573-2568}, mesh = {Adult ; Anti-Bacterial Agents/adverse effects ; Bacterial Proteins/genetics ; Bacterial Toxins/genetics ; Clostridioides difficile/genetics/*isolation &amp; purification ; Colectomy ; Colon/diagnostic imaging/*microbiology/pathology/surgery ; Compartment Syndromes/microbiology ; Enterocolitis, Pseudomembranous/diagnostic imaging/*microbiology/pathology/surgery ; Feces/microbiology ; Female ; Humans ; Ileostomy ; Immunosuppressive Agents/adverse effects ; Liver Transplantation/*adverse effects ; Multiple Organ Failure/microbiology ; Polymerase Chain Reaction ; Radiography, Abdominal ; Treatment Outcome ; }, }
@article {pmid20631100, year = {2010}, author = {Jeulin, H and Salmon, A and Bordigoni, P and Venard, V}, title = {Comparison of in-house real-time quantitative PCR to the Adenovirus R-Gene kit for determination of adenovirus load in clinical samples.}, journal = {Journal of clinical microbiology}, volume = {48}, number = {9}, pages = {3132-3137}, pmid = {20631100}, issn = {1098-660X}, mesh = {Adenoviridae Infections/*virology ; Adenoviruses, Human/*isolation &amp; purification ; Automation/methods ; Blood/virology ; Cerebrospinal Fluid/virology ; DNA, Viral/genetics/isolation &amp; purification ; Feces/virology ; Humans ; Polymerase Chain Reaction/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; Viral Load/*methods ; }, abstract = {In the context of hematopoietic stem cell transplantation, adenovirus infections are associated with relevant mortality and morbidity. Detection of adenovirus DNA by quantitative PCR is the "gold standard" for these patients. A total of 150 samples, namely, 78 whole-blood, 22 cerebrospinal fluid, 24 digestive biopsy, and 26 stool samples, from 29 patients, including 24 hematopoietic stem cell transplant recipients, were tested for the detection of adenovirus using an in-house real-time quantitative PCR assay (A. Heim, C. Ebnet, G. Harste, and P. Pring-Akerblom, J. Med. Virol. 70:228-239, 2003) and the commercially available Adenovirus R-Gene kit. Adenovirus DNA was automatically isolated from whole-blood samples (Magna Pure LC system; Roche) or was manually extracted from other specimens (QIAamp; Qiagen) using the appropriate kit. The intra- and interassay reproducibilities and sensitivities were evaluated with cell culture supernatant dilutions. Of the 150 samples tested, 86 were found to be positive and 55 were found to be negative using both techniques. Nine (6%) discordant results were obtained. In most cases, discrepant results concerned samples with low viral loads. Quantitative results for all concordant positive samples were analyzed using the Spearman correlation test. A good correlation between the results of the in-house assay and those of the kit assay was obtained (r = 0.95; P < 0.001). Regarding the threshold cycle value for internal control spiked samples, none of the 150 samples tested contained a PCR inhibitor. In conclusion, a relevant correlation of results between the in-house assay and the kit assay, as well as the high-quality reproducibility and sensitivity of the kit assay, warranted its use for follow-up of hematopoietic stem cell transplantation recipients.}, }
@article {pmid20619394, year = {2011}, author = {Eguchi, S and Takatsuki, M and Hidaka, M and Soyama, A and Ichikawa, T and Kanematsu, T}, title = {Perioperative synbiotic treatment to prevent infectious complications in patients after elective living donor liver transplantation: a prospective randomized study.}, journal = {American journal of surgery}, volume = {201}, number = {4}, pages = {498-502}, doi = {10.1016/j.amjsurg.2010.02.013}, pmid = {20619394}, issn = {1879-1883}, mesh = {Adult ; Aged ; Bacterial Infections/*prevention &amp; control ; Elective Surgical Procedures/adverse effects ; Feces/microbiology ; Female ; Humans ; Liver Transplantation/*methods ; *Living Donors ; Male ; Middle Aged ; Perioperative Care/*methods ; Postoperative Complications/*prevention &amp; control ; Prospective Studies ; *Synbiotics ; Treatment Outcome ; }, abstract = {BACKGROUND: Although the effect of synbiotic therapy using prebiotics and probiotics has been reported in hepatobiliary surgery, there are no reports of the effect on elective living-donor liver transplantation (LDLT).<br><br>METHODS: Fifty adult patients undergoing LDLT between September 2005 and June 2009 were randomized into a group receiving 2 days of preoperative and 2 weeks of postoperative synbiotic therapy (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides [the BLO group]) and a group without synbiotic therapy (the control group). Postoperative infectious complications were recorded as well as fecal microflora before and after LDLT in each group.<br><br>RESULTS: Only 1 systemic infection occurred in the BLO group (4%), whereas the control group showed 6 infectious complications (24%), with 3 cases of sepsis and 3 urinary tract infections with Enterococcus spp (P = .033 vs BLO group). No other type of complication showed any difference between the groups.<br><br>CONCLUSIONS: Infectious complications after elective LDLT significantly decreased with the perioperative administration of synbiotic therapy.}, }
@article {pmid20601895, year = {2010}, author = {Floch, MH}, title = {Fecal bacteriotherapy, fecal transplant, and the microbiome.}, journal = {Journal of clinical gastroenterology}, volume = {44}, number = {8}, pages = {529-530}, doi = {10.1097/MCG.0b013e3181e1d6e2}, pmid = {20601895}, issn = {1539-2031}, mesh = {Clostridioides difficile/isolation &amp; purification ; Clostridium Infections/microbiology/therapy ; Diarrhea/microbiology/therapy ; Feces/*microbiology ; Humans ; *Metagenome ; Treatment Outcome ; }, }
@article {pmid20567111, year = {2010}, author = {Hagiwara, S and Hagiwara, S and Asahara, T and Nomoto, K and Morotomi, M and Ishizuka, N and Miwa, A and O Yoshida, T}, title = {[Altered gut bacterial flora and organic acids in feces of patients undergoing autologous stem cell transplantation with quinolone-based antibacterial prophylaxis].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {37}, number = {6}, pages = {1075-1079}, pmid = {20567111}, issn = {0385-0684}, mesh = {Acids/analysis ; *Antibiotic Prophylaxis ; Fatty Acids, Volatile/analysis ; Feces/*chemistry/*microbiology ; Female ; Gastrointestinal Tract/microbiology ; Gram-Negative Bacterial Infections/*prevention &amp; control ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Male ; Middle Aged ; Organic Chemicals/*analysis ; Quinolones/*therapeutic use ; Transplantation, Homologous/adverse effects ; Treatment Outcome ; }, abstract = {Gastrointestinal toxicity and various infections are serious problems associated with high-dose chemotherapy. Antibacterial chemoprophylaxis reduces the incidence of gram-negative bacterial infection; however, it may affect the normal intestinal flora and induce drug resistance in organisms. We evaluated the chronological changes in fecal bacteria and organic acids in 6 patients undergoing autologous stem cell transplantation with quinolone-based chemoprophylaxis. All patients developed grade 2-3 diarrhea. Four patients developed grade 3 febrile neutropenia. The total count of obligatory anaerobic bacteria was significantly decreased on Day 7, but total facultative anaerobic bacterial count did not change throughout transplantation. However, Enterobacteriaceae and Lactobacillus were decreased on Day 7 and Staphylococcus was increased after transplantation. Total organic acid concentration and short-chain fatty acids were decreased on Day 7. The bacterial flora and organic acids in the gut were significantly altered in patients who underwent autologous stem cell transplantation with quinolonebased chemoprophylaxis. These changes may contribute to gastrointestinal toxicity and infections.}, }
@article {pmid20565365, year = {2010}, author = {Badiee, P and Alborzi, A and Vojdani, R and Shakiba, E and Rasouli, M and Ravanfar, P and Haddadi, P}, title = {Early diagnosis of systemic candidiasis in bone marrow transplant recipients.}, journal = {Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation}, volume = {8}, number = {2}, pages = {98-103}, pmid = {20565365}, issn = {2146-8427}, mesh = {Adolescent ; Adult ; Anti-Infective Agents/therapeutic use ; Bone Marrow Transplantation/*adverse effects ; Candida/classification/genetics/*isolation &amp; purification ; Candidiasis/*diagnosis/diagnostic imaging/etiology/microbiology ; Child ; Child, Preschool ; Cross-Sectional Studies ; DNA, Fungal/blood ; DNA, Ribosomal/blood ; Early Diagnosis ; Female ; Humans ; Immunosuppressive Agents/adverse effects ; Iran ; Male ; Middle Aged ; *Polymerase Chain Reaction ; Predictive Value of Tests ; Prospective Studies ; Ribotyping/*methods ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVES: Systemic candidiasis, are common infections during the neutropenic phase. The aim of this study was to identify quantitative Candida species ribosomal DNA using TaqMan technology for diagnosing candidiasis and monitoring them during hospitalization.<br><br>MATERIALS AND METHODS: During the prospective, cross-sectional study, from September 2006 to September 2007, a total of 375 clinical blood specimens were collected from 35 patients with hematologic disorders once a week pretransplant and posttransplant. Patients were evaluated for systemic candidiasis during hospitalization. Cultures from the throat, urine, feces, and sputum, along with sonography and computerized tomographic scans, were done when patients were febrile and not having a response to antibiotics. All samples were cultured on Sabouraud dextrose agar with chloramphenicol, and direct, microscopic examination was performed. Blood samples were cultured by bedside inoculation into BACTEC medium at 35 degrees C for 7 days. Clinical blood specimens were evaluated for Candida infections using the TaqMan-based PCR assay.<br><br>RESULTS: Of the 35 recipients, 6 had multiple samples that were TaqMan-positive with Candida species probe, 3 had 1 PCR positive-result in their blood samples, and the 26 recipients showed negative results. Fungal rDNA was found in 2 patients before and after transplant. All 6 patients with systemic candidiasis had microbiologic and/or radiologic evidence of Candida infections.<br><br>CONCLUSIONS: It seems that TaqMan-based PCR assay can serve as an accurate method for diagnosing and monitoring Candida infections. This is the first report of its kind that shows Candida infections can be present in the blood of the bone marrow transplant candidates, so closer observation of the recipients who are neutropenic and receive immunosuppressive drugs seems warranted to improve their chances for survival.}, }
@article {pmid20551752, year = {2010}, author = {Schwandner, T and König, IR and Heimerl, T and Kierer, W and Roblick, M and Bouchard, R and Unglaube, T and Holch, P and Ziegler, A and Kolbert, G}, title = {Triple target treatment (3T) is more effective than biofeedback alone for anal incontinence: the 3T-AI study.}, journal = {Diseases of the colon and rectum}, volume = {53}, number = {7}, pages = {1007-1016}, doi = {10.1007/DCR.0b013e3181db7738}, pmid = {20551752}, issn = {1530-0358}, mesh = {Anal Canal/*physiopathology ; Biofeedback, Psychology/*methods ; Defecation ; Electric Stimulation Therapy/*methods ; Electromyography/methods ; Fecal Incontinence/diagnosis/physiopathology/*therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Patient Compliance ; Quality of Life ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE: The efficacy of EMG-biofeedback and low-frequency electrical stimulation for the treatment of anal incontinence has not been proven. Our purpose was to evaluate a novel therapeutic concept, termed triple target treatment, which combines amplitude-modulated medium-frequency stimulation and EMG-biofeedback.<br><br>METHODS: Patients with anal incontinence were randomly assigned to the triple target regimen or EMG-biofeedback alone for a 9-month treatment period in a multicenter randomized clinical trial with blinded observers (ClincialTrials.gov registration number NCT00525291). Primary end points were changes in the Cleveland Clinic score and the adapted St. Mark's (Vaizey) score at 9 months compared with baseline. Secondary end points included therapy acceptance and proportion of patients achieving continence or improvement in grade or frequency of incontinence.<br><br>RESULTS: We enrolled 158 patients with anal incontinence. The median decrease in the Cleveland Clinic score from baseline to 9 months was 3 points greater for the triple target regimen than for EMG-biofeedback (95% CI, 1-4; P = .0024). The improvement was 8 points for the triple target regimen (95% CI, 7-9) and 5 points for EMG-biofeedback (95% CI, 4-7). Results were similar for the Vaizey score. Of patients treated for at least 3 months, continence was achieved by 50% of patients with the triple target regimen and 25.8% of those with EMG-biofeedback.<br><br>CONCLUSIONS: The combination of amplitude-modulated medium-frequency electrostimulation with EMG-biofeedback in the triple target regimen is superior to EMG-biofeedback alone in the treatment of anal incontinence. Therapy programs for fecal incontinence are most effective if patients participate for longer than 2 to 3 months.}, }
@article {pmid20547640, year = {2010}, author = {Russell, G and Kaplan, J and Ferraro, M and Michelow, IC}, title = {Fecal bacteriotherapy for relapsing Clostridium difficile infection in a child: a proposed treatment protocol.}, journal = {Pediatrics}, volume = {126}, number = {1}, pages = {e239-42}, doi = {10.1542/peds.2009-3363}, pmid = {20547640}, issn = {1098-4275}, mesh = {Anti-Bacterial Agents/administration &amp; dosage ; Child, Preschool ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/*therapy ; Combined Modality Therapy ; Diarrhea/*microbiology/*therapy ; *Drug Resistance, Multiple, Bacterial ; Drug Therapy, Combination ; Feces/*microbiology ; Female ; Follow-Up Studies ; Humans ; Naturopathy/*methods ; Probiotics/administration &amp; dosage ; Recurrence ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {Clostridium difficile infection (CDI) is a potentially serious emerging infectious disease. The incidences of CDI in childhood and CDI cases complicated by relapses have increased by 50% or more in North America during the past 2 decades. We report here the case of a 2-year-old child with relapsing CDI caused by the epidemic strain BI/NAP1/O27 that was refractory to Saccharomyces boulardii and Lactobacillus rhamnosus GG probiotics and to intensive therapy with traditional (metronidazole, vancomycin) and experimental (rifaximin, nitazoxanide) antibiotics despite its apparent antimicrobial-susceptible phenotype. After excluding other infectious causes of diarrhea and inflammatory bowel disease, we designed a protocol to safely administer fecal bacteriotherapy via a temporary nasogastric tube. We demonstrated for the first time that fecal transplantation is practical and effective for treating relapsing CDI in a young child. We recommend that this strategy be reserved for complicated cases of CDI that fail conventional therapy until randomized studies can confirm the safety and effectiveness of fecal bacteriotherapy in children.}, }
@article {pmid20517294, year = {2010}, author = {Liang, J and Gu, F and Wang, H and Hua, B and Hou, Y and Shi, S and Lu, L and Sun, L}, title = {Mesenchymal stem cell transplantation for diffuse alveolar hemorrhage in SLE.}, journal = {Nature reviews. Rheumatology}, volume = {6}, number = {8}, pages = {486-489}, pmid = {20517294}, issn = {1759-4804}, mesh = {Female ; Hemoptysis/etiology/*therapy ; Humans ; Lupus Erythematosus, Systemic/complications/*therapy ; *Mesenchymal Stem Cell Transplantation ; Pulmonary Alveoli/pathology ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: A 19-year-old girl was diagnosed with systemic lupus erythematosus, based on findings of arthritis, malar rash, positive antinuclear antibody test and high levels of antibodies to double-stranded DNA. Two months after diagnosis, the patient presented with a sudden drop in blood hemoglobin level. Several days later, she developed bloody sputum, rapidly progressive dyspnea and hypoxemia. High-resolution CT showed diffuse alveolar infiltrates in both lung fields.<br><br>INVESTIGATIONS: Physical examination, complete blood count, erythrocyte sedimentation rate, urinalysis, 24-h urine protein excretion, fecal occult blood test, d-dimer test, acid hemolysis test, activated partial thromboplastin time and prothrombin time, direct and indirect Coombs tests, bone marrow smear, arterial blood gas, sputum smear and culture, and high-resolution CT scan of the chest.<br><br>DIAGNOSIS: Diffuse alveolar hemorrhage associated with systemic lupus erythematosus.<br><br>MANAGEMENT: The patient did not respond to pulsed intravenous methylprednisolone (two courses of 500 mg per day for 3 days) and intravenous immunoglobulin (20 g per day for 5 days). The patient was referred to a specialist treatment center for allogenic transplantation using umbilical-cord-derived mesenchymal stem cells. She underwent transplantation with an infusion of 8 x 10(7) mesenchymal stem cells. After showing dramatic improvements in her clinical condition, oxygenation level, radiographic and hematological status, the patient was discharged from hospital approximately 5 weeks after undergoing transplantation.}, }
@article {pmid20501001, year = {2010}, author = {Hardwicke, J and Wright, TC and Hargest, R and Dickson, W}, title = {The use of the Flexi-Seal Faecal Management System in laparostomy wounds involving enterocutaneous fistula.}, journal = {Annals of the Royal College of Surgeons of England}, volume = {92}, number = {4}, pages = {W12-4}, pmid = {20501001}, issn = {1478-7083}, mesh = {Abdomen/surgery ; Aged ; Catheters, Indwelling ; Enterostomy/*instrumentation/methods ; Humans ; Intestinal Fistula/etiology/*surgery ; Male ; Skin Transplantation/methods ; Wound Healing ; }, abstract = {We present an innovative application of the Flexi-Seal Faecal Management System (FMS) for the diversion of upper and lower gastrointestinal secretions from enterocutaneous fistulae associated with complex wounds. Fistula is a common complication after the formation of a laparostomy, secondary to cases of severe intra-abdominal sepsis, acute mesenteric ischaemia, necrotising infection of the abdominal wall, or intra-abdominal hypertension. A significant mortality rate is associated with such fistula. With the successful continent diversion of gastrointestinal secretions by the Flexi-Seal FMS, abdominal wounds can be successfully skin-grafted, and wound healing expedited.}, }
@article {pmid20498923, year = {2010}, author = {Guimarães, VA and Atik, E and Castelli, JB and Ikari, NM and Thomaz, AM and Lopes, AA}, title = {[Association of plastic bronchitis to protein-losing enteropathy after fontan operation].}, journal = {Arquivos brasileiros de cardiologia}, volume = {94}, number = {4}, pages = {e109-12}, doi = {10.1590/s0066-782x2010000400024}, pmid = {20498923}, issn = {1678-4170}, mesh = {Bronchitis/*etiology ; Child, Preschool ; Female ; Fontan Procedure/*adverse effects ; Heart Ventricles/abnormalities ; Humans ; Protein-Losing Enteropathies/*etiology ; }, abstract = {We report an unusual case of association of plastic bronchitis (PB) to protein-losing enteropathy (PLE) in a girl of 4 years and 9 months of age with double inlet single left ventricle and ventriculoarterial concordance. submitted to total cavopulmonary surgery. with an intracardiac lateral tunnel at the age of three. The elimination of the 10 cm fibrin bronchial mold (PB) and the alpha-1-antitrypsin elevation of 52 mg/g in feces had both become outstanding. Using sildenafil. the thoracic duct ligature and the cardiac transplant were programmed in case of continuity of the process.}, }
@article {pmid20497144, year = {2010}, author = {Zerbib, P and Koriche, D and Truant, S and Bouras, AF and Vernier-Massouille, G and Seguy, D and Pruvot, FR and Cortot, A and Colombel, JF}, title = {Pre-operative management is associated with low rate of post-operative morbidity in penetrating Crohn's disease.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {32}, number = {3}, pages = {459-465}, doi = {10.1111/j.1365-2036.2010.04369.x}, pmid = {20497144}, issn = {1365-2036}, mesh = {Abscess/surgery ; Adolescent ; Adult ; Aged ; Antibiotic Prophylaxis ; Crohn Disease/*surgery ; Enteral Nutrition ; Female ; Humans ; Male ; Middle Aged ; Postoperative Complications/*surgery ; Preoperative Care/*adverse effects ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Ileocaecal resection for penetrating Crohn's disease is still challenging with a high rate of post-operative morbidity and faecal diversion.<br><br>AIM: To report retrospectively the results of pre-operative management for penetrating Crohn's disease focusing on the rate of post-operative major morbidities and need for faecal diversion.<br><br>METHODS: Between 1997 and 2007, 78 patients with penetrating Crohn's disease underwent a first ileocaecal resection after a pre-operative management consisting in bowel rest, nutritional therapy, intravenous antibiotics, weaning off steroids and immunosuppressors, and drainage of abscesses when appropriate.<br><br>RESULTS: Resection was performed for terminal ileitis associated with (n = 41), abscesses (n = 37) or both (n = 5). A pre-operative nutritional therapy was performed in 50 patients (68%) for 23 days (range, 7-69 days) along with a weaning off steroids and immunosuppressors. A diverting stoma was performed for six patients (7.7%). There was no post-operative death. Post-operative complications were classified as minor in 10 patients (12.8%), and major in four patients (5%). Overall, the post-operative course was uneventful in 58 patients (74%).<br><br>CONCLUSION: Pre-operative management for penetrating Crohn's disease allowed ileocaecal resection with low rates of post-operative morbidity and faecal diversion.}, }
@article {pmid20489630, year = {2010}, author = {Sindhi, R and AshokKumar, C and Mazariegos, G and Nayyar, N and Ningappa, M and Soltys, K and Bond, G and Sun, Q and Humar, A and Abu-Elmagd, K and Zeevi, A}, title = {Immune monitoring in small bowel transplantation.}, journal = {Current opinion in organ transplantation}, volume = {15}, number = {3}, pages = {349-356}, doi = {10.1097/MOT.0b013e328339489c}, pmid = {20489630}, issn = {1531-7013}, mesh = {Biological Assay ; Cytotoxicity Tests, Immunologic ; Drug Monitoring ; Genetic Markers ; Graft Rejection/genetics/immunology/*prevention &amp; control ; *Graft Survival ; Histocompatibility Testing ; Humans ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Inflammation Mediators/metabolism ; Intestine, Small/immunology/*transplantation ; Lymphocyte Activation ; Lymphocyte Count ; *Monitoring, Immunologic/methods ; Polymorphism, Single Nucleotide ; Predictive Value of Tests ; Short Bowel Syndrome/*surgery ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Immune monitoring is needed in small bowel transplantation (SBTx) because of a high incidence of rejection and graft loss, and life-threatening complications of high-dose prophylactic immunosuppression.<br><br>RECENT FINDINGS: Clinical tests relevant to SBTx include methods to detect antidonor human leukocyte antigen antibodies, among which those which use known purified human leukocyte antigen peptides as substrates correlate best with graft loss; enumerate peripheral lymphocyte subsets to determine the efficacy of lymphocyte-depleting antibodies; estimate general immune function based on ATP production by mitogen-stimulated T-helper cells. Research tests that show clinical utility in SBTx recipients include following markers. First, flow cytometric mixed leukocyte responses, which detect donor-induced proliferation of recipient T-cytotoxic cells by dilution of the intravital dye carboxyfluorescein succinimidyl ester, or donor-induced CD154 expression in recipient T-cytotoxic memory cells. Among such tests, CD154 T-cytotoxic memory cells achieve the highest known sensitivity and specificity of at least 90% for the detection of acute cellular rejection. Second, elevated fecal calprotectin, an early screening marker for intestinal inflammation, which can indicate the need for a SBTx biopsy, especially after ileostomy stoma closure. Third, single-nucleotide polymorphisms associated with inflammatory bowel diseases, for example, nucleotide-binding oligomerization protein, macrophage stimulating 1, and so on. These single-nucleotide polymorphisms may be used to select the rejection-prone SBTx recipient for more potent immunosuppression, if additional studies confirm their associations with outcomes.<br><br>SUMMARY: The final approach to monitor the SBTx recipient will likely involve using the method(s) with the best sensitivity and specificity for detecting acute cellular rejection or graft loss during time periods when such events are most likely.}, }
@article {pmid20485184, year = {2010}, author = {Rohlke, F and Surawicz, CM and Stollman, N}, title = {Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology.}, journal = {Journal of clinical gastroenterology}, volume = {44}, number = {8}, pages = {567-570}, doi = {10.1097/MCG.0b013e3181dadb10}, pmid = {20485184}, issn = {1539-2031}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {GOALS: Recurrent Clostridium difficile infection (RCDI) is an increasingly common clinical problem without ideal treatment options. Our aim was to evaluate our results using Fecal Flora Reconstitution (FFR), and promulgate our methodology to the GI community to foster its more widespread use in appropriate candidates.<br><br>BACKGROUND: FFR, sometimes termed "fecal transplantion" has been shown in numerous reports to be an effective treatment of RCDI, however, most of these studies have small sample sizes and few focus specifically on the methodology used in colonoscopic preparation and delivery of donated stool.<br><br>STUDY: Nineteen patients with confirmed multiply recurrent CDI were treated by infusing donor stool through a colonoscope.<br><br>RESULTS: Out of 19 patients, 18 initially responded to treatment with a single FFR treatment, 1 patient responded after a second FFR infusion. All 19 patients maintained prolonged cured status followed until submission, ranging from 6 months to 5 years. Three patients were presumed reinfected after remaining symptom free for a period spanning from 6 months to 4 years. These patients tested positive for C. difficile after prescription of additional antibiotics for unrelated infections.<br><br>CONCLUSIONS: Fecal Flora Reconstitution is an effective, viable, and simple method of treatment for the difficult to treat patients with RCDI who fail standard therapy.}, }
@article {pmid20483789, year = {2010}, author = {Herbert, DR and Orekov, T and Roloson, A and Ilies, M and Perkins, C and O'Brien, W and Cederbaum, S and Christianson, DW and Zimmermann, N and Rothenberg, ME and Finkelman, FD}, title = {Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {184}, number = {11}, pages = {6438-6446}, pmid = {20483789}, issn = {1550-6606}, support = {R01 GM083204/GM/NIGMS NIH HHS/United States ; R01 GM083204-03/GM/NIGMS NIH HHS/United States ; R01GM083204/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Arginase/*immunology/metabolism ; Cell Differentiation ; Cell Separation ; Coculture Techniques ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Immunohistochemistry ; Inflammation/*immunology/metabolism ; Interleukin-12/*immunology/metabolism ; Interleukin-23/*immunology/metabolism ; Intestinal Mucosa/immunology/metabolism/pathology ; Lymphocyte Activation/immunology ; Macrophage Activation/immunology ; Macrophages/immunology/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Receptors, Interleukin-4/immunology/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Schistosomiasis mansoni/*immunology/metabolism ; T-Lymphocytes/cytology/immunology/metabolism ; Transplantation Chimera ; }, abstract = {Alternatively activated macrophages prevent lethal intestinal pathology caused by worm ova in mice infected with the human parasite Schistosoma mansoni through mechanisms that are currently unclear. This study demonstrates that arginase I (Arg I), a major product of IL-4- and IL-13-induced alternatively activated macrophages, prevents cachexia, neutrophilia, and endotoxemia during acute schistosomiasis. Specifically, Arg I-positive macrophages promote TGF-beta production and Foxp3 expression, suppress Ag-specific T cell proliferation, and limit Th17 differentiation. S. mansoni-infected Arg I-deficient bone marrow chimeras develop a marked accumulation of worm ova within the ileum but impaired fecal egg excretion compared with infected wild-type bone marrow chimeras. Worm ova accumulation in the intestines of Arg I-deficient bone marrow chimeras was associated with intestinal hemorrhage and production of molecules associated with classical macrophage activation (increased production of IL-6, NO, and IL-12/IL-23p40), but whereas inhibition of NO synthase-2 has marginal effects, IL-12/IL-23p40 neutralization abrogates both cachexia and intestinal inflammation and reduces the number of ova within the gut. Thus, macrophage-derived Arg I protects hosts against excessive tissue injury caused by worm eggs during acute schistosomiasis by suppressing IL-12/IL-23p40 production and maintaining the Treg/Th17 balance within the intestinal mucosa.}, }
@article {pmid20463588, year = {2010}, author = {Yoon, SS and Brandt, LJ}, title = {Treatment of refractory/recurrent C. difficile-associated disease by donated stool transplanted via colonoscopy: a case series of 12 patients.}, journal = {Journal of clinical gastroenterology}, volume = {44}, number = {8}, pages = {562-566}, doi = {10.1097/MCG.0b013e3181dac035}, pmid = {20463588}, issn = {1539-2031}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Colonoscopy/*methods ; Diarrhea/microbiology/therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {PURPOSE AND OBJECTIVE: Over the past 20 years, Clostridium difficile has emerged as an important microbial cause of nosocomial diarrhea. Recurrence is common and management of recurrent disease is not standardized. In this case series, we describe 12 patients with refractory/recurrent C. difficile-associated disease (CDAD) treated at our institution by transplantation of donated stool via colonoscopy.<br><br>METHODS: This is a retrospective study of 12 consecutive patients with refractory/recurrent C. difficile infection evidenced by recurrent symptoms and a history of a positive fecal C. difficile toxin assay that were treated by transplantation of donated stool administered during colonoscopy.<br><br>RESULTS: Our cohort comprised 9 women and 3 men with a mean age of 66 years (range 30 to 86 y). Nine of the 12 patients had diverticulosis. Patients were symptomatically ill for 79 to 1532 days (mean 351 d, median 209 d) before fecal transplantation. The index infection for which antibiotics was prescribed varied widely along with the inciting antibiotic. All 12 patients (100%) experienced an immediate and durable clinical response to fecal transplantation. There were no adverse side effects from fecal transplantation.<br><br>CONCLUSIONS: Fecal transplantation via colonoscopy is a safe, effective treatment regimen for refractory/recurrent CDAD. Our 12 patients had an immediate and durable response rate of 100%. Fecal transplantation is a promising treatment for refractory/recurrent C. difficile infection. Its use and efficacy should be pursued in prospective controlled trials.}, }
@article {pmid20428648, year = {2010}, author = {Azami, M and Sharifi, M and Hejazi, SH and Tazhibi, M}, title = {Intestinal parasitic infections in renal transplant recipients.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {14}, number = {1}, pages = {15-18}, doi = {10.1590/s1413-86702010000100004}, pmid = {20428648}, issn = {1678-4391}, mesh = {Adult ; Aged ; Case-Control Studies ; Cross-Sectional Studies ; Feces/*parasitology ; Female ; Humans ; Immunocompromised Host ; Intestinal Diseases, Parasitic/*epidemiology/immunology/parasitology ; Iran/epidemiology ; *Kidney Transplantation ; Male ; Middle Aged ; Prevalence ; Young Adult ; }, abstract = {The impact of intestinal parasitic infection in renal transplant recipients requires careful consideration in the developing world. However, there have been very few studies addressing this issue in Iran. This study was conducted to determine the prevalence of intestinal parasitic infections in renal transplant recipients in Iran. Stool specimens from renal transplant recipients and control groups were obtained between June 2006 and January 2007. The samples screened for intestinal parasitic infections using direct smear, formalin-ether sedimentation, Sheather's flotation and modified Ziehl-Neelsen staining methods. Out of 150 renal transplant recipients, 33.3% (50), and out of 225 control group, 20% (45) were infected with one or more type of intestinal parasites. The parasites detected among patients included Entamoeba coli (10.6%), Endolimax nana (8.7%), Giardia lamblia (7.4%), Blastocystis spp. (4.7%), Iodamoeba butschlii (0.7%), Chilomastix mesnili (0.7%) and Ascaris lumbricoides (0.7%). Multiple infections were more common among renal transplant recipients group (p < 0.05). This study highlights the importance of testing for intestinal parasites among Iranian renal transplant recipients. Routine examinations of stool samples for parasites would significantly benefit the renal transplant recipients by contributing to reduce severe infections.}, }
@article {pmid20368178, year = {2009}, author = {Turnbaugh, PJ and Ridaura, VK and Faith, JJ and Rey, FE and Knight, R and Gordon, JI}, title = {The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice.}, journal = {Science translational medicine}, volume = {1}, number = {6}, pages = {6ra14}, pmid = {20368178}, issn = {1946-6242}, support = {R01 DK070977/DK/NIDDK NIH HHS/United States ; R01 DK070977-06/DK/NIDDK NIH HHS/United States ; DK70977/DK/NIDDK NIH HHS/United States ; }, mesh = {Adiposity ; Animals ; Bacteria/genetics ; *Diet ; Energy Metabolism ; *Genomics ; Germ-Free Life ; Humans ; Intestines/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Diet and nutritional status are among the most important modifiable determinants of human health. The nutritional value of food is influenced in part by a person's gut microbial community (microbiota) and its component genes (microbiome). Unraveling the interrelations among diet, the structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by variations in human environmental exposures, microbial ecology, and genotype. To help overcome these problems, we created a well-defined, representative animal model of the human gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into germ-free C57BL/6J mice. Culture-independent metagenomic analysis of the temporal, spatial, and intergenerational patterns of bacterial colonization showed that these humanized mice were stably and heritably colonized and reproduced much of the bacterial diversity of the donor's microbiota. Switching from a low-fat, plant polysaccharide-rich diet to a high-fat, high-sugar "Western" diet shifted the structure of the microbiota within a single day, changed the representation of metabolic pathways in the microbiome, and altered microbiome gene expression. Reciprocal transplants involving various combinations of donor and recipient diets revealed that colonization history influences the initial structure of the microbial community but that these effects can be rapidly altered by diet. Humanized mice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobiotic mice will be useful for conducting proof-of-principle "clinical trials" that test the effects of environmental and genetic factors on the gut microbiota and host physiology. Nearly full-length 16S rRNA gene sequences are deposited in GenBank under the accession numbers GQ491120 to GQ493997.}, }
@article {pmid20368177, year = {2009}, author = {Flier, JS and Mekalanos, JJ}, title = {Gut check: testing a role for the intestinal microbiome in human obesity.}, journal = {Science translational medicine}, volume = {1}, number = {6}, pages = {6ps7}, doi = {10.1126/scitranslmed.3000483}, pmid = {20368177}, issn = {1946-6242}, mesh = {Animals ; Germ-Free Life ; Humans ; Intestines/*microbiology ; Mice ; Obesity/*microbiology ; }, abstract = {By using germ-free mice transplanted with human fecal microbiota, scientists show that a high-fat, high-sugar diet durably changes the transplanted microbiome and that this diet-altered microbiome promotes obesity. This model should encourage investigation of the gut microbiome as a contributor to human metabolic disease and permit discovery of targets for the prevention and treatment of these disorders.}, }
@article {pmid20361153, year = {2010}, author = {Heine T, C and Parada C, MT and Gil D, R and López K, F and Lizana S, C and Fernández A, M and Quera P, R}, title = {[Distal intestinal obstruction syndrome: report of two cases with cystic fibrosis].}, journal = {Revista medica de Chile}, volume = {138}, number = {1}, pages = {68-72}, pmid = {20361153}, issn = {0034-9887}, mesh = {Adolescent ; Adult ; Cystic Fibrosis/*surgery ; Female ; Humans ; Ileal Diseases/*etiology ; Intestinal Obstruction/*etiology ; Lung Transplantation/*adverse effects ; Male ; Syndrome ; }, abstract = {Distal Intestinal Obstruction Syndrome (DIOS) has a 16% incidence among patients with Cystic Fibrosis (CF). It is characterized by an intestinal obstruction secondary to fecal impaction in distal ileum or cecum. We report two adult patients with DIOS. A female with CF and subjected to lung transplantation at the age of 13 years old. Five years later, she consulted for an intestinal obstruction. She was treated conservatively with a good clinical evolution. She had a new episode of DIOS eight months later that was also treated conservatively. A 31 year-old mole, subjected to bilateral lung transplantation nine years before, that was admitted to the hospital for a bronchiolitis. Three days after admission he started with an intestinal obstruction that was diagnosed as a DIOS. He was managed conservatively with a good clinical response.}, }
@article {pmid20357431, year = {2010}, author = {Hosseini-Moghaddam, SM and Zarei, A and Alavian, SM and Mansouri, M}, title = {Hepatitis E virus infection: a general review with a focus on hemodialysis and kidney transplant patients.}, journal = {American journal of nephrology}, volume = {31}, number = {5}, pages = {398-407}, doi = {10.1159/000294505}, pmid = {20357431}, issn = {1421-9670}, mesh = {Antibodies, Viral/chemistry ; Global Health ; Hepatitis E/*epidemiology/*transmission/virology ; Hepatitis E virus/*metabolism ; Humans ; Kidney Transplantation/*methods ; Liver/enzymology/virology ; Renal Dialysis/*adverse effects ; Renal Insufficiency/complications ; Risk Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Hepatitis E virus (HEV) infection is a self-limited viral disease that causes acute hepatitis epidemics in developing countries. The common route of transmission for HEV is supposedly fecal-oral. Serological evidence may be unexpectedly found in hemodialysis (HD) patients and kidney transplant recipients. Although the route of HEV transmission is not usually determined in HD subjects, this virus seems to be transmitted either directly through HD or nosocomially. In this study, we gathered the published information on HEV infection in HD patients and kidney transplant recipients.<br><br>METHODS: For this review, we collected the relevant articles by searching through Medline and Google Scholar from January 1980 up to September 2009.<br><br>RESULTS: Some variables including older age, low education, living in rural versus urban areas and the duration of HD seem to be risk factors for HEV infection in HD patients. Compared with non-HD subjects, HEV infection may be specifically associated with poor outcome in HD patients. Specific considerations seem to be required to prevent transmission of HEV to HD patients.<br><br>CONCLUSION: More extensive investigations are required to determine the disease burden of HEV infection in HD subjects in countries which experience outbreaks of HEV infection.}, }
@article {pmid20345613, year = {2010}, author = {Haveman, LM and de Jager, W and van Loon, AM and Claas, EC and Prakken, BJ and Bierings, M}, title = {Different cytokine signatures in children with localized and invasive adenovirus infection after stem cell transplantation.}, journal = {Pediatric transplantation}, volume = {14}, number = {4}, pages = {520-528}, doi = {10.1111/j.1399-3046.2009.01263.x}, pmid = {20345613}, issn = {1399-3046}, mesh = {Adenovirus Infections, Human/*blood/immunology ; Adolescent ; Biomarkers/blood ; Child ; Child, Preschool ; Cytokines/*blood/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Male ; Polymerase Chain Reaction ; Postoperative Complications/*blood/immunology ; Prospective Studies ; Statistics, Nonparametric ; *Stem Cell Transplantation ; Viremia/immunology ; }, abstract = {HAdV infection is a dangerous complication after pediatric SCT. In this study, we aimed at determining the cytokine profile in plasma samples in case of HAdV infection after SCT to gain more knowledge about the HAdV-specific immune response. In this prospective study, 47 pediatric SCT recipients were included in three yr. By using particle-based MIA, 17 different cytokines were analyzed in 41 plasma samples of patients with a localized HAdV infection (presence of HAdV in feces, urine or throat detected by culture) and patients with invasive HAdV infection (HAdV viremia in blood, detected by PCR). In patients with invasive HAdV infection, but not in patients with localized HAdV infection, the pro-inflammatory cytokines IL1beta, IL6, IL8, IL12, IFNgamma, TNFalpha, and also IL17, MIP1alpha, OSM, and IP10 were produced. The simultaneous release of the cytokines IL1beta, IL17, IL18, OSM, MIP1alpha, and IP10 was related to invasive HAdV infections. We also show that cytokine signatures can be helpful to differentiate invasive HAdV infection from GvHD and EBV infections. In conclusion, after SCT, children with invasive HAdV infection have a different cytokine profile compared with patients with a localized HAdV infection.}, }
@article {pmid20222891, year = {2010}, author = {Reddy, S and Taori, S and Poxton, IR}, title = {Changes in laboratory and clinical workload for Clostridium difficile infection from 2003 to 2007 in hospitals in Edinburgh.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {16}, number = {4}, pages = {340-346}, doi = {10.1111/j.1469-0691.2010.03141.x}, pmid = {20222891}, issn = {1469-0691}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/diagnosis/*epidemiology ; Feces/microbiology ; Hospitalization/statistics &amp; numerical data ; Humans ; Incidence ; Infant ; Infant, Newborn ; Laboratories, Hospital/statistics &amp; numerical data ; Middle Aged ; Retrospective Studies ; Scotland/epidemiology ; Young Adult ; }, abstract = {Clostridium difficile infection (CDI) is a growing concern with regard to increases in incidence and its associated financial burden. A retrospective analysis of patients admitted to Hospitals in Edinburgh from 2003 to 2007 and tested for C. difficile toxins was performed. A total of 45 412 faecal samples were tested and 6286 (13.8%) were positive. Overall CDI was identified in 1.7 cases/1000 in-patient occupied bed days (OBD). The incidence of CDI fell from 1.98 cases/1000 OBD in 2006 to 1.48 cases/1000 OBD in 2007. Renal Medicine, including Transplant Surgery, and Intensive Care had the highest incidence, with >6.2 cases/1000 OBD each, followed by Infectious Diseases and Gastrointestinal Medicine, with rates of 5.5 and 4.42 cases/1000 OBD, respectively. Medicine of the Elderly had an incidence of 1.69 cases/1000 OBD. Incidence increased with age, from 0.45 cases/1000 OBD in the 0-20-year-old age group to 2.02 cases/1000 OBD in the 61-80-year-old age group. Twelve percent of all toxin-positive patients were transferred through a minimum of two specialties when they remained positive for C. difficile toxins. Estimated costs over the study period for toxin testing were approximately pound126 500 and the minimal potential hospitalization costs for patients with CDI was pound20 000 000. The overall incidence of patients identified with CDI fell in 2007 compared to 2006. The incidence has increased with age; however, patients in Medicine of the Elderly had a much lower incidence than in several other specialties and therefore risk assessment of CDI should also be targeted within other specialties. Judicious application of infection control measures remains important for preventing CDI.}, }
@article {pmid20220559, year = {2010}, author = {Friedman, JD and Reece, GR and Eldor, L}, title = {The utility of the posterior thigh flap for complex pelvic and perineal reconstruction.}, journal = {Plastic and reconstructive surgery}, volume = {126}, number = {1}, pages = {146-155}, doi = {10.1097/PRS.0b013e3181da8769}, pmid = {20220559}, issn = {1529-4242}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Pelvis/*surgery ; Perineum/*surgery ; Plastic Surgery Procedures/*methods ; Retrospective Studies ; Surgical Flaps/*statistics &amp; numerical data ; Thigh/*surgery ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Complex wounds of the pelvis and perineum commonly occur as a result of primary and secondary ablative procedures for colorectal and gynecologic malignancies, particularly following previous radiation therapy to these regions. In certain instances, the more traditional flaps such as the vertical rectus abdominis and gracilis flaps are either unavailable or unsuitable for the reconstruction of particular defects. The posterior thigh flap has been described previously for pelvic defects but has not become as widely accepted as other regional flaps.<br><br>METHODS: This study sought to retrospectively review the authors' experience with the posterior thigh flap as an alternative to these more commonly performed transfers for difficult wounds of the perineum and pelvic structures. A total of 27 posterior thigh flaps were used in 19 patients for complex perineal wound closure.<br><br>RESULTS: Successful transfer of the posterior thigh flap was noted in 26 of 27 flaps (11 unilateral and eight bilateral), with only one flap failure (3.7 percent). Primary wound healing was ultimately achieved in all patients; however, early wound-healing complications were common (53 percent). Secondary procedures were necessary in seven patients (37 percent), with only one patient requiring a secondary flap procedure.<br><br>CONCLUSIONS: The authors found the posterior thigh flap to be a useful and reliable flap for coverage of complex perineal wounds. This was particularly true for those patients in whom a laparotomy was best avoided and those who have had both urinary and fecal diversion.}, }
@article {pmid20172281, year = {2010}, author = {Cagnola, H and Scaravonati, R and Cabanne, A and Bianchi, C and Gruz, F and Errea, A and Zambernardi, A and Meier, D and Chirdo, F and Docena, G and Gondolesi, G and Rumbo, M}, title = {Evaluation of calprotectin level in intestinal content as an early marker for graft rejection.}, journal = {Transplantation proceedings}, volume = {42}, number = {1}, pages = {57-61}, doi = {10.1016/j.transproceed.2009.12.013}, pmid = {20172281}, issn = {1873-2623}, mesh = {Adolescent ; Adult ; Biomarkers/analysis/metabolism ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay/methods ; Feces/chemistry ; Graft Rejection/*diagnosis ; Humans ; Infant ; Leukocyte L1 Antigen Complex/*analysis ; Middle Aged ; ROC Curve ; Retrospective Studies ; Transplantation, Homologous ; }, abstract = {INTRODUCTION: The diagnosis of rejection after intestinal transplantation is still performed by endoscopic biopsy monitoring. Less invasive diagnostic procedures are desirable, although they are not available so far. Calprotectin, a stable cytosolic granulocyte protein, which previously was used as a marker of inflammatory processes, has been proposed to be a biochemical marker for rejection. The aim of the present work was to analyze the concordance between calprotectin levels in intestinal content and the presence of graft rejection after small bowel transplantation.<br><br>METHODS: Calprotectin level was measured using a commercial ELISA kit on 137 samples of intestinal content randomly collected during endoscopies performed on 11 intestinal transplantation patients during 2 years' follow-up. Calprotectin determinations were correlated with histological and clinical findings. The cut-off level was determined retrospectively by receiver-operator curve analysis.<br><br>RESULTS: Based on histological findings and clinical records, samples were discerned as rejection positive (37 of 137), versus negative (35 of 137) samples or those with no clinical, endoscopic, or histological findings (65 of 137 samples). A cut-off value of 65 microg of calprotectin/g of intestinal content provided the best assay parameter according to the clinical findings: a 76% sensitivity and a 47% specificity. False positive results corresponded to patients with gastrointestinal infections (13%), systemic infections (13%), ulcers (10%), or nonspecific histological alterations of the mucosa (15%). The other false positive cases corresponded to postsurgical samples (4%), or patients with concomitant gastrointestinal symptoms (2%). Most false negative results (78%) were observed during recovery from severe acute rejection episodes, among successfully treated patients. In these cases, epithelial reconstitution and no mucosal infiltration was observed. If the latter group were discarded, sensitivity rose to 93%, and specificity, to 50% with a 96% negative predictive value. Furthermore, a weak correlation was observed between calprotectin levels and the severity of rejection.<br><br>CONCLUSIONS: This study confirmed the results obtained by other groups: fecal calprotectin dosage showed a good sensitivity but low specificity for the diagnosis of intestinal rejection because high calprotectin levels can also be observed in other clinical conditions. Nevertheless, it might be used as a first line for continuous evaluation of intestinal transplantation status, like other biochemical parameters that are used in kidney or liver transplantation, before considering the need for a biopsy.}, }
@article {pmid20172013, year = {2010}, author = {Joly, F and Mayeur, C and Bruneau, A and Noordine, ML and Meylheuc, T and Langella, P and Messing, B and Duée, PH and Cherbuy, C and Thomas, M}, title = {Drastic changes in fecal and mucosa-associated microbiota in adult patients with short bowel syndrome.}, journal = {Biochimie}, volume = {92}, number = {7}, pages = {753-761}, doi = {10.1016/j.biochi.2010.02.015}, pmid = {20172013}, issn = {1638-6183}, mesh = {Adult ; Case-Control Studies ; Clostridium/genetics/isolation &amp; purification ; Cohort Studies ; Feces/*microbiology ; Humans ; Intestinal Mucosa/*microbiology ; Lactobacillus/genetics/isolation &amp; purification ; *Metagenome ; Middle Aged ; Nutritional Status ; Short Bowel Syndrome/*microbiology/pathology/physiopathology ; }, abstract = {Short bowel syndrome (SBS) is observed in Humans after a large resection of gut. Since the remnant colon and its associated microbiota play a major role in the outcome of patients with SBS, we studied the overall qualitative and quantitative microbiota composition of SBS adult patients compared to controls. The population was composed of 11 SBS type II patients (with a jejuno-colonic anastomosis) and 8 controls without intestinal pathology. SBS patients had 38 +/- 30 cm remnant small bowel length and 66 +/- 19% of residual colon. The repartition of proteins, lipids, carbohydrates and fibres was expressed as % of total oral intake in patients and controls. The microbiota was profiled from stool and biopsy samples with temporal temperature gradient gel electrophoresis and quantitative PCR. We show here that microbiota of SBS patients is unbalanced with a high prevalence of Lactobacillus along with a sub-dominant presence and poor diversity of Clostridium leptum, Clostridium coccoides and Bacteroidetes. In addition, Lactobacillus mucosae was detected within the fecal and mucosa-associated microbiota of SBS patients, whereas it remained undetectable in controls. Thus, in SBS the microbial composition was deeply altered in fecal and mucosal samples, with a shift between dominant and sub-dominant microbial groups and the prevalence of L. mucosae.}, }
@article {pmid20147979, year = {2010}, author = {Lion, T and Kosulin, K and Landlinger, C and Rauch, M and Preuner, S and Jugovic, D and Pötschger, U and Lawitschka, A and Peters, C and Fritsch, G and Matthes-Martin, S}, title = {Monitoring of adenovirus load in stool by real-time PCR permits early detection of impending invasive infection in patients after allogeneic stem cell transplantation.}, journal = {Leukemia}, volume = {24}, number = {4}, pages = {706-714}, doi = {10.1038/leu.2010.4}, pmid = {20147979}, issn = {1476-5551}, mesh = {Adenoviridae/genetics/*isolation &amp; purification ; Adenovirus Infections, Human/*diagnosis/etiology ; Adolescent ; Adult ; Child ; Child, Preschool ; DNA, Viral/genetics ; Feces/*virology ; Graft Rejection/diagnosis/mortality ; Graft Survival/genetics ; Humans ; Incidence ; Infant ; Leukemia/genetics/*therapy/virology ; Lymphoma/genetics/*therapy/virology ; *Polymerase Chain Reaction ; Prospective Studies ; Sensitivity and Specificity ; *Stem Cell Transplantation ; Survival Rate ; Transplantation, Homologous ; Treatment Outcome ; Viral Load ; Viremia/diagnosis/etiology ; Young Adult ; }, abstract = {Invasive adenovirus (AdV) infections are associated with high morbidity and mortality in allogeneic stem cell transplant recipients. We observed that molecular detection of the virus in stool specimens commonly precedes AdV viremia, suggesting that intestinal infections may represent a common source of virus dissemination. To address this notion, we have investigated 153 consecutive allogeneic transplantations in 138 pediatric patients by quantitative monitoring of AdV in stool specimens and peripheral blood by a pan-adenovirus real-time (RQ)-PCR approach. AdV was detectable in serial stool specimens in all cases of AdV viremia during the post-transplant course (P<0.0001). The incidence of AdV viremia in individuals with peak virus levels in stool specimens above 1 x 10E6 copies per gram (n=22) was 73% vs 0% in patients with AdV levels in stool specimens below this threshold (n=29; P<0.0001). Serial measurement of AdV levels in stool specimens by RQ-PCR permitted early diagnosis of impending invasive infection with a sensitivity and specificity of 100% (95% confidence interval (CI) 96-100%) and 83% (95% CI 67-92%), respectively. The median time span between detection of AdV loads in stool specimens above 1 x 10E6 copies per gram and first observation of viremia was 11 days (range 0-192). Quantitative monitoring of the AdV load in stool specimens therefore provides a rationale for early initiation of antiviral treatment with the aim of preventing progression to life-threatening invasive infection.}, }
@article {pmid20122011, year = {2009}, author = {Rubin, TA and Gessert, CE and Aas, J}, title = {Stool transplantation for older patients with Clostridium difficile infection.}, journal = {Journal of the American Geriatrics Society}, volume = {57}, number = {12}, pages = {2386}, doi = {10.1111/j.1532-5415.2009.02600.x}, pmid = {20122011}, issn = {1532-5415}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*administration &amp; dosage ; *Clostridioides difficile/drug effects ; Clostridium Infections/*therapy ; Drug Administration Schedule ; Feces/*microbiology ; Humans ; Omeprazole/*administration &amp; dosage ; *Probiotics ; Recurrence ; Vancomycin/*administration &amp; dosage ; }, }
@article {pmid20117243, year = {2010}, author = {Silverman, MS and Davis, I and Pillai, DR}, title = {Success of self-administered home fecal transplantation for chronic Clostridium difficile infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {8}, number = {5}, pages = {471-473}, doi = {10.1016/j.cgh.2010.01.007}, pmid = {20117243}, issn = {1542-7714}, mesh = {Administration, Rectal ; Adult ; Aged ; Aged, 80 and over ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; *Feces ; Female ; Humans ; Male ; Middle Aged ; Self Administration/*methods ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Clostridium difficile infection (CDI) can relapse in patients with significant comorbidities. A subset of these patients becomes dependent on oral vancomycin therapy for prolonged periods with only temporary clinical improvement. These patients incur significant morbidity from recurrent diarrhea and financial costs from chronic antibiotic therapy.<br><br>METHODS: We sought to investigate whether self- or family-administered fecal transplantation by low volume enema could be used to definitively treat refractory CDI.<br><br>RESULTS: We report a case series (n = 7) where 100% clinical success was achieved in treating these individuals with up to 14 months of follow-up.<br><br>CONCLUSIONS: Fecal transplantation by low volume enema is an effective and safe option for patients with chronic relapsing CDI, refractory to other therapies. Making this approach available in health care settings has the potential to dramatically increase the number of patients who could benefit from this therapy.}, }
@article {pmid20107217, year = {2010}, author = {Patel, NC and Hertel, PM and Estes, MK and de la Morena, M and Petru, AM and Noroski, LM and Revell, PA and Hanson, IC and Paul, ME and Rosenblatt, HM and Abramson, SL}, title = {Vaccine-acquired rotavirus in infants with severe combined immunodeficiency.}, journal = {The New England journal of medicine}, volume = {362}, number = {4}, pages = {314-319}, pmid = {20107217}, issn = {1533-4406}, support = {M01 RR000188/RR/NCRR NIH HHS/United States ; M01 RR-00188/RR/NCRR NIH HHS/United States ; R01 AI080656/AI/NIAID NIH HHS/United States ; K12 HD041648/HD/NICHD NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; K12 HD41648/HD/NICHD NIH HHS/United States ; }, mesh = {DNA, Viral/analysis ; Dehydration/etiology ; Diarrhea, Infantile/etiology ; Failure to Thrive/etiology ; Feces/virology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; RNA, Viral/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Rotavirus/genetics/*isolation &amp; purification ; Rotavirus Infections/*etiology/virology ; Rotavirus Vaccines/*adverse effects ; Sequence Alignment ; Sequence Analysis, DNA ; Severe Combined Immunodeficiency/*complications/therapy ; Stem Cell Transplantation ; Virus Shedding ; }, abstract = {Live pentavalent human-bovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and diarrhea within 1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, in stool specimens obtained from all three infants, and gene-sequence analysis revealed the presence of vaccine rotavirus. These infections raise concerns regarding the safety of rotavirus vaccine in severely immunocompromised patients.}, }
@article {pmid20101195, year = {2010}, author = {Sasbón, JS and Buamscha, D and Gianivelli, S and Imventarza, O and Devictor, D and Moreiro, R and Cambaceres, C and Salip, G and Ciocca, M and Cuarterolo, M and Vladimirsky, S and Otegui, L and Castro, R and Brajterman, L and Soto, S and González, J and Munné, MS}, title = {Clinical implications of hepatitis A virus ribonucleic acid detection and genotyping in acute liver failure in children in Argentina.}, journal = {Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies}, volume = {11}, number = {3}, pages = {385-389}, doi = {10.1097/PCC.0b013e3181ceadca}, pmid = {20101195}, issn = {1529-7535}, mesh = {Adolescent ; Argentina/epidemiology ; Child ; Child, Preschool ; Feces/virology ; Female ; *Genotype ; Hepatitis A/*diagnosis/epidemiology ; Hepatitis A virus/*genetics/*isolation &amp; purification ; Humans ; Infant ; Intensive Care Units, Pediatric ; Liver Failure, Acute/*etiology/virology ; Male ; Observation ; RNA/*blood ; }, abstract = {OBJECTIVES: To investigate the detection of hepatitis A virus ribonucleic acid in patients with acute liver failure and to assess if the results have any clinical implications for the evolution of acute liver failure in children. Hepatitis A infection, a vaccine-preventable disease, is an important cause of acute liver failure in children in Argentina. Universal vaccination in 1-yr-old children was implemented in June 2005.<br><br>DESIGN: Observational study in which patients were divided into Group 1 consisting of positive hepatitis A virus ribonucleic acid and Group 2 consisting of negative hepatitis A virus ribonucleic acid.<br><br>SETTING: Pediatric intensive care unit in National Pediatric Hospital "Dr. J. P. Garrahan," Buenos Aires, Argentina.<br><br>PATIENTS: Thirty-three patients with the diagnosis of acute liver failure secondary to hepatitis A virus infection and admitted to the Garrahan Pediatric Hospital between September 2003 and September 2005 were enrolled in the study. Twenty of these children were admitted to the pediatric intensive care unit.<br><br>INTERVENTIONS: None.<br><br>MEASUREMENTS AND MAIN RESULTS: Samples for total ribonucleic acid detection and genotyping were obtained from serum and/or stools on admission. We found positive hepatitis A virus ribonucleic acid in 13 patients and negative hepatitis A virus ribonucleic acid in 20 patients. The following clinical variables were evaluated: time of evolution, hospital stay, admission to the pediatric intensive care unit, pediatric intensive care unit stay, time on mechanical ventilation, criteria for orthotopic liver transplantation, and mortality. Characterization of the isolates did not reveal differences related to genotype; all cases were IA. No statistical significance was found as to the variables. However, positive hepatitis A virus ribonucleic acid showed lower percentages of pediatric intensive care unit admissions, criteria for orthotopic liver transplantation, number of orthotopic liver transplantation, and mortality than the group of patients with negative hepatitis A virus ribonucleic acid.<br><br>CONCLUSIONS: Hepatitis A virus genotyping studies did not show any particularities, all cases were IA and, thus, apparent associations between genotype and the clinical presentation of acute liver failure could not be found.}, }
@article {pmid20096660, year = {2010}, author = {Kamar, N and Abravanel, F and Mansuy, JM and Peron, JM and Izopet, J and Rostaing, L}, title = {[Hepatitis E infection in dialysis and after transplantation].}, journal = {Nephrologie &amp; therapeutique}, volume = {6}, number = {2}, pages = {83-87}, doi = {10.1016/j.nephro.2009.10.005}, pmid = {20096660}, issn = {1872-9177}, mesh = {Developed Countries ; Developing Countries ; France/epidemiology ; Hepatitis E/*diagnosis/*epidemiology/transmission/virology ; *Hepatitis E virus/isolation &amp; purification ; Humans ; *Immunocompromised Host ; Immunosuppressive Agents/administration &amp; dosage/*adverse effects ; Incidence ; *Kidney Transplantation ; Liver Cirrhosis/virology ; Prevalence ; *Renal Dialysis ; }, abstract = {Hepatitis E virus (HEV) causes epidemics of acute hepatitis in developing countries, and also appears to be an emerging agent in industrialized countries. HEV infection is transmitted via the fecal-oral route, and may be a zoonosis in industrialized countries. HEV infection was thought to be responsible for acute hepatitis that does not become chronic. However, it has been recently reported that HEV infection can evolve to chronic hepatitis and to cirrhosis, at least in solid-organ transplant patients. The reduction of immunosuppressive drugs could be considered as a first-line therapeutic option.}, }
@article {pmid20048681, year = {2010}, author = {Khoruts, A and Dicksved, J and Jansson, JK and Sadowsky, MJ}, title = {Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea.}, journal = {Journal of clinical gastroenterology}, volume = {44}, number = {5}, pages = {354-360}, doi = {10.1097/MCG.0b013e3181c87e02}, pmid = {20048681}, issn = {1539-2031}, mesh = {Clostridioides difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/chemically induced/microbiology/*therapy ; Feces/*microbiology ; Female ; Follow-Up Studies ; Humans ; *Metagenome ; Middle Aged ; Polymorphism, Restriction Fragment Length ; RNA, Ribosomal, 16S ; Sequence Analysis, RNA ; }, abstract = {Clostridium difficile-associated disease (CDAD) is the major known cause of antibiotic-induced diarrhea and colitis, and the disease is thought to result from persistent disruption of commensal gut microbiota. Bacteriotherapy by way of fecal transplantation can be used to treat recurrent CDAD, which is thought to reestablish the normal colonic microflora. However, limitations of conventional microbiologic techniques have, until recently, precluded testing of this idea. In this study, we used terminal-restriction fragment length polymorphism and 16S rRNA gene sequencing approaches to characterize the bacterial composition of the colonic microflora in a patient suffering from recurrent CDAD before and after treatment by fecal transplantation from a healthy donor. Although the patient's residual colonic microbiota, prior to therapy was deficient in members of the bacterial divisions-Firmicutes and Bacteriodetes, transplantation had a dramatic impact on the composition of the patient's gut microbiota. By 14 days posttransplantation, the fecal bacterial composition of the recipient was highly similar to that of the donor and was dominated by Bacteroides spp. strains and an uncharacterized butyrate producing bacterium. The change in bacterial composition was accompanied by resolution of the patient's symptoms. The striking similarity of the recipient's and donor's intestinal microbiota following after bacteriotherapy suggests that the donor's bacteria quickly occupied their requisite niches resulting in restoration of both the structure and function of the microbial communities present.}, }
@article {pmid20042046, year = {2009}, author = {Bakri, MM and Sutherland, AD and Brown, DJ and Vesely, P and Crossan, C and Scobie, L}, title = {Assessment of the potential risk of infection associated with Clostridium difficile from porcine xenografts.}, journal = {Xenotransplantation}, volume = {16}, number = {6}, pages = {472-476}, doi = {10.1111/j.1399-3089.2009.00538.x}, pmid = {20042046}, issn = {1399-3089}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Clostridioides difficile/drug effects/*pathogenicity ; Enterocolitis, Pseudomembranous/*etiology/microbiology ; Feces/microbiology ; Humans ; Microbial Sensitivity Tests ; Risk Assessment ; Risk Factors ; Skin/microbiology ; Swine ; Transplantation, Heterologous/*adverse effects ; Zoonoses ; }, abstract = {There are numerous concerns over the potential for transfer of pathogens between species during clinical xenotransplantation, and although current clinical application is limited, porcine xenografts have been previously used to treat patients with severe burns. Donor animals providing the xenografts are sourced from a healthy commercial herd, however, as pigs are a known source of zoonotic agents, a number of diseases are required to be excluded from pigs used for xenotransplantation purposes. Many studies have indicated the relevance of viral zoonoses, however, little has been done with regard to the potential for transfer of pathogens related to health care associated infections. Clostridium difficile is a major cause of neonatal enteritis in pigs and an important feature of this organism is that pigs can be asymptomatic carriers. This study has examined the incidence of C. difficile PCR ribotypes present in healthy donor pigs to determine if pig faeces, and in particular, contamination of skin with faecal matter, is a potential route for the transfer of C. difficile. Animals were found to have human ribotype 017 present in the faecal matter, however, no C. difficile was isolated from skin samples taken from the same animals. In addition, due to the risk factors associated with C. difficile infection, the antimicrobial susceptibility of the C. difficile isolates has been determined.}, }
@article {pmid20041927, year = {2011}, author = {Abbes Orabi, N and Vanwymersch, T and Paterson, HM and Mauel, E and Jamart, J and Crispin, B and Kartheuser, A}, title = {Total perineal reconstruction after abdominoperineal excision for rectal cancer: long-term results of dynamic graciloplasty with Malone appendicostomy.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {13}, number = {4}, pages = {406-413}, doi = {10.1111/j.1463-1318.2009.02168.x}, pmid = {20041927}, issn = {1463-1318}, mesh = {Adenocarcinoma/psychology/*surgery ; Adult ; Enterostomy/adverse effects/*methods ; Fecal Incontinence/etiology/surgery ; Female ; Humans ; Male ; Middle Aged ; Perineum/*surgery ; Prospective Studies ; Quality of Life ; Plastic Surgery Procedures/adverse effects/*methods ; Rectal Neoplasms/psychology/*surgery ; Surveys and Questionnaires ; Treatment Outcome ; }, abstract = {AIM: This study aimed to assess long-term function after total perineal reconstruction (TPR) with dynamic graciloplasty (DG) and systematic Malone appendicostomy (MA) adjunction after abdominoperineal excision (APR) for rectal cancer.<br><br>METHOD: From 1999 to 2004, TPR using DG and MA was performed in 10 patients [seven women; median age 40 (range 28-55) years] after APR for rectal cancer (cT2 in one patient, cT3 in six patients and cT4 in three patients). We prospectively recorded early and late morbidity, mortality, oncological outcome, functional results (using the modified Working Party on Anal Sphincter Replacement 'WPASR' scoring system) and quality of life (QoL; using the European Organisation for Research and Treatment of Cancer 'EORTC' QLQ-C30 and QLQ-CR38 questionnaires).<br><br>RESULTS: There was no procedure-related mortality. One patient required intra-abdominal re-operation. Nine patients required local and multiple revisions [there was one coloperineal anastomosis (CPA) stenosis, five CPA mucosal prolapse, three stenosis related to graciloplasty, two MA stenosis and one MA reflux]. After a median follow up of 78 months, there was no local recurrence and six patients were alive and disease-free. Regarding the functional results, the median modified WPASR score, of 8, after a follow up of 78 months, was good. The overall QoL scores remained stable over time.<br><br>CONCLUSION: In carefully selected patients who want to avoid definitive abdominal colostomy after APR for rectal cancer, reconstruction involving MA and DG after APR for low rectal cancer is followed by good long-term function and QoL.}, }
@article {pmid20025828, year = {2010}, author = {Hashimoto, K and Uchikawa, R and Tegoshi, T and Takeda, K and Yamada, M and Arizono, N}, title = {Immunity-mediated regulation of fecundity in the nematode Heligmosomoides polygyrus--the potential role of mast cells.}, journal = {Parasitology}, volume = {137}, number = {5}, pages = {881-887}, doi = {10.1017/S0031182009991673}, pmid = {20025828}, issn = {1469-8161}, mesh = {Animals ; Chemokine CCL2/blood ; Feces/parasitology ; Female ; Fertility/*immunology ; Male ; Mast Cells/cytology/*immunology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mice, SCID ; Nematospiroides dubius/cytology/*immunology ; Parasite Egg Count ; Specific Pathogen-Free Organisms ; Strongylida Infections/*immunology ; }, abstract = {Previous studies have shown that host immunity regulates the fecundity of nematodes. The present study was aimed at clarifying the reversible nature of fecundity in response to changes of immunological status and to determine which effector cells are responsible for compromising fecundity in Heligmosomoides polygyrus. Enhanced fecundity was observed in immunocompromised SCID and nu/nu mice compared to those in the corresponding wild-type mice, with significantly fewer numbers of intrauterine eggs produced in the wild-type than in the immunodeficient mice. When 14-day-old adult worms from BALB/c mice were transplanted into naïve BALB/c mice, their fecundity increased significantly as early as 24 h post-transplantation, but not when they were transferred into immune mice, suggesting the plastic and reversible nature of fecundity in response to changes in host immunological status. In mast cell-deficient W/W(v) mice, nematode fecundity was significantly higher than in mast cell-reconstituted W/W(v) or +/+ mice. The serum levels of the mast-cell protease mMCP1 were markedly increased in the wild-type as well as the mast cell-reconstituted W/W(v), but not in the W/W(v), SCID, or nu/nu mice during infection. These findings raise the interesting possibility that certain activities of mast cells, either directly or indirectly, regulate parasite fecundity during infection.}, }
@article {pmid19967262, year = {2010}, author = {Fram, D and Castrucci, FM and Taminato, M and Godoy-Martinez, P and Freitas, MC and Belasco, A and Sesso, R and Pacheco-Silva, A and Pignatari, AC and Barbosa, D}, title = {Cross-transmission of vancomycin-resistant Enterococcus in patients undergoing dialysis and kidney transplant.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {43}, number = {1}, pages = {115-119}, doi = {10.1590/s0100-879x2009007500023}, pmid = {19967262}, issn = {1414-431X}, mesh = {Cross Infection/*microbiology ; Cross-Sectional Studies ; Enterococcus/classification/*drug effects/isolation &amp; purification ; Feces/microbiology ; Humans ; Kidney Transplantation/*adverse effects ; Renal Dialysis/*adverse effects ; Ribotyping ; *Vancomycin Resistance ; }, abstract = {The objective of this study was to investigate the occurrence of vancomycin-resistant Enterococcus (VRE) cross-transmission between two patient groups (long-term dialysis and kidney transplant patients). Molecular typing, by automated ribotyping with the RiboPrinter Microbial Characterization System (Qualicon, USA), was used to analyze VRE isolates from 31 fecal samples of 320 dialysis patients and 38 fecal samples of 280 kidney transplant patients. Clonal spread of E. faecalis and E. casseliflavus was observed intragroup, but not between the two groups of patients. In turn, transmission of E. gallinarum and E. faecium between the groups was suggested by the finding of vancomycin-resistant isolates belonging to the same ribogroup in both dialysis and transplant patients. The fact that these patients were colonized by VRE from the same ribogroup in the same health care facility provides evidence for cross-transmission and supports the adoption of stringent infection control measures to prevent dissemination of these bacteria.}, }
@article {pmid19966609, year = {2009}, author = {Aghaee-Afshar, M and Rezazadehkermani, M and Asadi, A and Malekpour-Afshar, R and Shahesmaeili, A and Nematollahi-mahani, SN}, title = {Potential of human umbilical cord matrix and rabbit bone marrow-derived mesenchymal stem cells in repair of surgically incised rabbit external anal sphincter.}, journal = {Diseases of the colon and rectum}, volume = {52}, number = {10}, pages = {1753-1761}, doi = {10.1007/DCR.0b013e3181b55112}, pmid = {19966609}, issn = {1530-0358}, mesh = {Anal Canal/*injuries/physiopathology ; Animals ; Bone Marrow Cells/*cytology ; Disease Models, Animal ; Electromyography ; Fecal Incontinence/physiopathology/*therapy ; Humans ; Male ; Mesenchymal Stem Cell Transplantation/*methods ; Muscle Contraction ; Rabbits ; Random Allocation ; Statistics, Nonparametric ; Umbilical Cord/*cytology ; }, abstract = {PURPOSE: Anal sphincter defects and fecal incontinence are complicated surgical problems. We investigated the ability of human umbilical cord matrix (hUCM) and rabbit bone marrow (rBM) stem cells to improve anal sphincter incontinence due to induced sphincter defects without surgical repair.<br><br>METHODS: We harvested hUCM cells from human Wharton's jelly and rBM stem cells from rabbit femurs and tibias. To induce sphincter defects, we made an incision in the external anal sphincter. Rabbits were randomly allocated to 5 groups to receive either no intervention (n = 3) or injections of 10 hUCM cells in medium (10 microL RPMI-1640), rBM cells in medium, medium only, or normal saline (n = 7 per group), 2 weeks after sphincterotomy. Transplanted cells were tracked in the injured sphincters by prelabeling with bromodeoxyuridine. Electromyography was performed before and 2 weeks after the external anal sphincterotomy, and 2 weeks after cell transplantation. We also evaluated the proliferation and differentiation of injected cells with histopathologic techniques.<br><br>RESULTS: Electromyography showed significant improvement in sphincter function 2 weeks after local injection of rBM stem cells compared with pretreatment values and controls. Moderate, nonsignificant improvement was observed with hUCM cell injection. Cells with incorporated bromodeoxyuridine were detected at the site of injury after transplantation of hUCM and rBM. Histopathologic evaluation showed normal or muscle-dominant sphincter structure in all animals receiving rBM and fibrous-dominant sphincter structure in most animals receiving hUCM.<br><br>CONCLUSIONS: Stem cell injection at the site of injury can enhance contractile function of the anal sphincter without surgical repair. Transplantation of stem cells, particularly bone marrow mesenchymal cells, may provide an effective tool for treating anal sphincter injuries in humans.}, }
@article {pmid19910774, year = {2009}, author = {Schwab, JH and Healey, JH and Rose, P and Casas-Ganem, J and Boland, PJ}, title = {The surgical management of sacral chordomas.}, journal = {Spine}, volume = {34}, number = {24}, pages = {2700-2704}, doi = {10.1097/BRS.0b013e3181bad11d}, pmid = {19910774}, issn = {1528-1159}, mesh = {Chordoma/complications/pathology/*surgery ; Cryotherapy/statistics &amp; numerical data ; Disease-Free Survival ; Fecal Incontinence/epidemiology ; Female ; Humans ; Male ; Neoplasm Metastasis/pathology/physiopathology ; Neoplasm Recurrence, Local ; Neurosurgical Procedures/*methods/*statistics &amp; numerical data ; Polyradiculopathy/epidemiology ; Postoperative Complications/etiology/prevention &amp; control ; Radiography ; Radiotherapy/statistics &amp; numerical data ; Rectus Abdominis/transplantation ; Reoperation/statistics &amp; numerical data ; Retrospective Studies ; Sacrum/diagnostic imaging/pathology/*surgery ; Spinal Neoplasms/complications/pathology/*surgery ; Surgical Flaps/statistics &amp; numerical data ; Survival Rate ; Treatment Outcome ; Urinary Bladder, Neurogenic/epidemiology ; }, abstract = {STUDY DESIGN: Retrospective case series.<br><br>OBJECTIVE: The purpose of this study was to evaluate factors that contribute to improved local control and survival. In addition, we sought to define the expected morbidity associated with treatment.<br><br>SUMMARY OF BACKGROUND DATA: Sacral chordomas are rare tumors presumed to arise from notochordal cells. Local recurrence presents a major problem in the management of these tumors and it has been correlated with survival. Resection of sacral tumors is associated with significant morbidity.<br><br>METHODS: Forty-two patients underwent resection for sacral chordoma between 1990 and 2005. Twelve patients had their initial surgery elsewhere. There were 12 female and 30 male patients. The proximal extent of the sacrectomy was at least S2 in 32 patients.<br><br>RESULTS: Median survival was 84 months, and 5-year disease-free (DFS) and disease-specific survival (DSF) were 56% and 77%, respectively. Local recurrence (LR) and metastasis occurred in 17 (40%) and 13 (31%) patients, respectively. Local recurrence (P=0.0001), metastasis (P=0.0001), prior resection (P=0.046), and higher grade (P=0.05) were associated with a worse DSF. Prior resections (P=0.0001) and intralesional resections (P=0.01) were associated with a higher rate of LR. Intralesional resections were associated with a lower DSF (P=0.0001). Wide contaminated margins treated with cryosurgery and/or radiation were not associated with a higher LR rate. Rectus abdominus flaps were associated with decreased wound complications (P=0.01). Thirty-one (74%) patients reported that they self catheterize; and 16 (38%) patients required bowel training, while an additional twelve (29%) patients had a colostomy. Twenty-eight (67%) patients reported sexual dysfunction. Two (5%) patients died due to sepsis.<br><br>CONCLUSIONS: Intralesional resection should be avoided as it is associated with a higher LR rate and worse survival. Rectus abdominus flaps ought to be considered as they lower the wound complication rate. Sacral resection is associated with significant morbidity.}, }
@article {pmid19902263, year = {2010}, author = {Gonzalez-Granado, LI}, title = {Polymerase chain reaction for Cryptosporidium in the immunocompromised host.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {25}, number = {3}, pages = {569; author reply 571-2}, pmid = {19902263}, issn = {1432-198X}, mesh = {Antiparasitic Agents/therapeutic use ; Child ; Cryptosporidiosis/*diagnosis/drug therapy/parasitology ; Cryptosporidium parvum/*genetics ; Feces/parasitology ; Humans ; Immunocompromised Host/*physiology ; Kidney Transplantation/*immunology/physiology ; Reverse Transcriptase Polymerase Chain Reaction ; }, }
@article {pmid19875391, year = {2010}, author = {Frudinger, A and Kölle, D and Schwaiger, W and Pfeifer, J and Paede, J and Halligan, S}, title = {Muscle-derived cell injection to treat anal incontinence due to obstetric trauma: pilot study with 1 year follow-up.}, journal = {Gut}, volume = {59}, number = {1}, pages = {55-61}, doi = {10.1136/gut.2009.181347}, pmid = {19875391}, issn = {1468-3288}, support = {//Department of Health/United Kingdom ; }, mesh = {Adult ; Aged ; Anal Canal/diagnostic imaging/*injuries/physiopathology ; Cell Culture Techniques ; Endosonography ; Epidemiologic Methods ; Fecal Incontinence/diagnostic imaging/etiology/physiopathology/*therapy ; Female ; Humans ; Myoblasts, Skeletal/*transplantation ; *Obstetric Labor Complications ; Pregnancy ; Pressure ; Psychometrics ; Quality of Life ; Treatment Outcome ; Ultrasonography, Interventional ; }, abstract = {OBJECTIVE: To treat anal incontinence due to obstetric external anal sphincter disruption via injection of autologous myoblast cells.<br><br>DESIGN: Observational pilot study.<br><br>SETTING: University hospital and district hospital<br><br>PATIENTS: 10 women suffering from anal incontinence due to obstetric anal sphincter injury, refractory to conventional non-surgical therapy.<br><br>INTERVENTIONS: Autologous myoblasts were cultured from a pectoralis muscle biopsy, harvested, and injected into the external anal sphincter defect using direct ultrasound guidance.<br><br>MAIN OUTCOME MEASURES: Wexner incontinence score, anal squeeze pressures, and quality of life 12 months after injection. Safety and technical feasibility.<br><br>RESULTS: The procedure was well tolerated and no adverse events were observed. At 12 months the Wexner incontince score had decreased by a mean of 13.7 units (95% CI, -16.3 to -11.2), anal squeeze pressures were unchanged, and overall quality of life scores improved by a median of 30 points (95% CI, 25 to 42). Anal squeeze pressures did rise significantly at 1 month and 6 months post-injection (p = 0.03).<br><br>CONCLUSIONS: Injection of autologous myoblasts is safe, well tolerated, and significantly improves symptoms of anal incontinence due to obstetric anal sphincter trauma.}, }
@article {pmid19863601, year = {2011}, author = {Altomare, DF and Rinaldi, M and Lobascio, P and Marino, F and Giuliani, RT and Cuccia, F}, title = {Factors affecting the outcome of temporary sacral nerve stimulation for faecal incontinence. The value of the new tined lead electrode.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {13}, number = {2}, pages = {198-202}, doi = {10.1111/j.1463-1318.2009.02088.x}, pmid = {19863601}, issn = {1463-1318}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/physiology ; Electric Stimulation Therapy/*instrumentation ; *Electrodes, Implanted ; Equipment Design ; Fecal Incontinence/etiology/*therapy ; Female ; Humans ; Lumbosacral Plexus/*physiology ; Male ; Manometry ; Middle Aged ; }, abstract = {AIM: Sacral nerve stimulation (SNS) is an effective but expensive treatment for faecal incontinence. About 50% of the patients are unresponsive for unknown reasons, hence knowledge of any factors predictive of success would be highly desirable. The aim of this study was to analyse the potential factors associated with a successful outcome of the temporary test of electrostimulation.<br><br>METHOD: Eighty-five patients with faecal incontinence were tested for SNS. The cause was idiopathic in 45, iatrogenic or obstetric in 28, spinal lesion or neurological diseases in nine and anal malformation in three patients; 43 were tested with a unipolar electrode and 42 with a quadripolar electrode. The severity of faecal incontinence was evaluated using the American Medical System (AMS) score and Wexner's score.<br><br>RESULTS: A positive response was obtained in 45 patients (53%); 40 (47%) were implanted with a permanent pulse generator. Responders and nonresponders were comparable in age, duration of incontinence, anal manometry, pudendal nerve terminal motor latency and diabetes. Unipolar electrode test (PNE test) was able to elicit positive responses in 18 of 43 (42%) and the quadripolar in 27 of 42 patients (P < 0.001). Type of incontinence and gender did not affect the success rate. Patients with idiopathic incontinence had a significantly higher response rate (P =0.022). Multivariate regression analysis indicated use of a quadripolar electrode as the only independent variable predicting the success of SNS (OR = 5.58, P = 0.009).<br><br>CONCLUSION: Use of the quadripolar electrode is the only factor significantly related to the success of SNS.}, }
@article {pmid19857727, year = {2009}, author = {Swoboda-Kopec, E and Netsvyetayeva, I and Paczek, L and Dabkowska, M and Kwiatkowski, A and Jaworska-Zaremba, M and Mierzwinska-Nastalska, E and Sikora, M and Blachnio, S and Mlynarczyk, G and Fiedor, P}, title = {Algorithm of clinical protocol lowering the risk of systemic Mycosis infections in allografts recipients.}, journal = {Transplantation proceedings}, volume = {41}, number = {8}, pages = {3264-3266}, doi = {10.1016/j.transproceed.2009.07.074}, pmid = {19857727}, issn = {1873-2623}, mesh = {*Algorithms ; Humans ; Kidney Transplantation/adverse effects ; Mycoses/blood/diagnosis/*epidemiology/*prevention &amp; control ; Pancreas Transplantation/adverse effects ; Shock, Septic/microbiology ; Transplantation, Homologous/*adverse effects ; }, abstract = {The aim of the study was to describe a diagnostic protocol to lower the risk of a mycotic invasive infection among allotransplant recipients and to suggest the use of preoperative prophylaxis and/or empiric therapy. We chose a group of 268 allograft recipients with transient or constant yeast colonization or confirmed yeast infection. Among 7744 clinical samples, 475 were positive for fungi. We used conventional fungal laboratory diagnosis, enzymatic activity tests, serologic tests, molecular diagnosis of samples from sterile body sites, and histopathologic examinations. The following clinical samples were examined: blood samples; swabs from mouth lesions, throat, and rectum; and sputum, urine, and fecal samples from kidney transplant recipients and simultaneous pancreas-kidney transplantation recipients who are highly predisposed to mycotic infections. We established microbiologic criteria of a systemic mycosis and principles to distinguish colonization from infection.}, }
@article {pmid19846336, year = {2010}, author = {Patel, S and Slatter, M and Valappil, M and Waugh, S}, title = {Persistent adenoviraemia in an infant following haematopoietic stem cell transplantation.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {47}, number = {1}, pages = {1-3}, doi = {10.1016/j.jcv.2009.09.022}, pmid = {19846336}, issn = {1873-5967}, mesh = {Adenoviridae/isolation &amp; purification ; Adenoviridae Infections/drug therapy/*immunology ; Antiviral Agents/therapeutic use ; Cidofovir ; Cytosine/analogs &amp; derivatives/therapeutic use ; Feces/virology ; Female ; *Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Lymphocyte Count ; Male ; Mothers ; Organophosphonates/therapeutic use ; Severe Combined Immunodeficiency/therapy/*virology ; Viral Load ; Viremia/drug therapy/*virology ; }, }
@article {pmid19832873, year = {2011}, author = {Altomare, DF and Greco, VJ and Tricomi, N and Arcanà, F and Mancini, S and Rinaldi, M and Pulvirenti d'Urso, A and La Torre, F}, title = {Seton or glue for trans-sphincteric anal fistulae: a prospective randomized crossover clinical trial.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {13}, number = {1}, pages = {82-86}, doi = {10.1111/j.1463-1318.2009.02056.x}, pmid = {19832873}, issn = {1463-1318}, mesh = {Anal Canal/surgery ; Chi-Square Distribution ; Cross-Over Studies ; Curettage ; Female ; Fibrin Tissue Adhesive/*therapeutic use ; Humans ; Length of Stay/statistics &amp; numerical data ; Male ; Middle Aged ; Pain Measurement ; Prospective Studies ; Rectal Fistula/surgery/*therapy ; Statistics, Nonparametric ; Treatment Outcome ; Wound Healing ; }, abstract = {OBJECTIVE: Fibrin glue treatment of anal fistulae has been proposed to minimize the risk of faecal incontinence but its acceptance by coloproctologists is still poor because the published data is controversial. Therefore, we carried out a prospective randomized crossover trial comparing treatment with a commercial fibrin glue to classical seton treatment, with healing rate, hospital stay, healing time, faecal incontinence and postoperative pain as study outcomes.<br><br>METHOD: Sixty-four homogeneous patients with trans-sphincteric anal fistulae referred to seven colorectal units were randomized to undergo fibrin glue (39 patients) or seton (25 patients) treatment. Patients failing to heal after treatment with fibrin glue were re-randomized to undergo a second injection with glue or seton treatment.<br><br>RESULTS: Sixty-two of the 64 patients completed the minimum 1-year follow-up period. Twenty-one of 24 patients healed in the seton group compared with 15/38 in the fibrin glue group (P = 0.0007). The 23 failures after glue treatment were re-randomized to have a second glue injection (eight patients) or a seton treatment (15 patients). Four of the eight (50%) patients treated with a second injection of glue, and nine out of the 15 (60%) patients in the seton group, healed. Patients treated with fibrin glue reported less postoperative pain and had a shorter hospital stay than patients treated with a seton; furthermore, faecal continence and anal manometry significantly worsened after seton treatment.<br><br>CONCLUSION: Seton treatment has a significantly higher probability of success compared with fibrin glue treatment but poses a higher risk of faecal incontinence. Fibrin glue could be considered as a first line of treatment for patients at risk of faecal incontinence or other comorbidities.}, }
@article {pmid19829289, year = {2009}, author = {Altomare, DF and Rinaldi, M and Cuccia, F and Lemma, M and Giuratrabocchetta, S and Giuliani, RT and De Fazio, M}, title = {Fecal incontinence: up to date on pathophysiology and treatment.}, journal = {Minerva gastroenterologica e dietologica}, volume = {55}, number = {3}, pages = {379-384}, pmid = {19829289}, issn = {1121-421X}, mesh = {Fecal Incontinence/etiology/*physiopathology/*therapy ; Humans ; }, abstract = {This study analyzes the most recent insight into the pathophysiology of fecal incontinence considering each of the factors contributing to the mechanism of fecal continence both during urgency to defecate and in resting state. In fact different types of incontinence are caused by different damage to one or more of these physiologic factors. The second part of the study focuses on the therapeutic choices of fecal incontinence. The recent introduction of sacral nerve electrostimulation and the progressive broadening of its clinical indications is progressively replacing and challenging other traditional surgical techniques because of their disappointing long-term results and because they are much more invasive. An emerging new treatment based on the injection of anal bulking agents is nowadays even more preferred for the less severe cases of fecal incontinence. An increasing number of materials is now proposed by the industry in order to identify the best biocompatible material to be injected trans-anally. Traditional surgery could be reserved for patients non-responding to these new treatments.}, }
@article {pmid19827425, year = {2009}, author = {Baumgartner, U}, title = {[Surgical options in fecal incontinence].}, journal = {MMW Fortschritte der Medizin}, volume = {151}, number = {37}, pages = {35-7; quiz 38}, doi = {10.1007/BF03365814}, pmid = {19827425}, issn = {1438-3276}, mesh = {Anal Canal/innervation/surgery ; Electric Stimulation Therapy/instrumentation ; Fecal Incontinence/etiology/*surgery ; Humans ; Lumbosacral Plexus/physiopathology ; Muscle, Skeletal/transplantation ; Prosthesis Design ; Prosthesis Implantation ; }, }
@article {pmid19784839, year = {2010}, author = {O'Reilly, T and McSheehy, PM and Kawai, R and Kretz, O and McMahon, L and Brueggen, J and Bruelisauer, A and Gschwind, HP and Allegrini, PR and Lane, HA}, title = {Comparative pharmacokinetics of RAD001 (everolimus) in normal and tumor-bearing rodents.}, journal = {Cancer chemotherapy and pharmacology}, volume = {65}, number = {4}, pages = {625-639}, doi = {10.1007/s00280-009-1068-8}, pmid = {19784839}, issn = {1432-0843}, mesh = {Animals ; Area Under Curve ; Cell Line, Tumor ; Everolimus ; Feces/chemistry ; Female ; Humans ; Immunosuppressive Agents/blood/*pharmacokinetics/urine ; Male ; Metabolic Clearance Rate ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasms, Experimental/blood/*metabolism/urine ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; Sirolimus/*analogs &amp; derivatives/pharmacokinetics ; Species Specificity ; Time Factors ; Tissue Distribution ; Transplantation, Heterologous ; }, abstract = {PURPOSE: Comparative pharmacokinetic (PK) analysis of the mTOR inhibitor RAD001 (everolimus) in rats and mice.<br><br>METHODS: Blood cell partitioning, plasma protein binding and PK parameters of RAD001 in blood and tissues (including brain) of both mice and rats were determined. PK modeling predicted plasma/blood and tumor levels from a variety of regimens and these were compared with the known human PK profile. DCE-MRI was used to compare tumor vascularity between mice and rats. Estimation of IC50 values in vitro and ED50 values in vivo were used to provide an indication of anti-tumor activity.<br><br>RESULTS: The PK properties of RAD001 differed between mice and rats, including erythrocyte partitioning, plasma protein binding, plasma/blood t(1/2), oral bioavailability, volume of distribution, tissue/tumor penetration and elimination. Modeling of tumor and blood/plasma PK suggested that in mice, multiple daily administrations result in a 2-fold increase in tumor levels of RAD001 at steady state, whereas in rats, a 7.9-fold increase would occur. Weekly high-dose regimens were predicted not to facilitate tumor accumulation in either species. Total tumor levels of RAD001 were four- to eight-fold greater in rats than in mice. Rat tumors had a >2-fold greater plasma content and permeability compared to mouse tumors, which could contribute to differences in tumor drug uptake. Maximal antitumor effects (T/C of 0.04-0.35) were observed in both species after daily administration with similar C(max) and AUC values of unbound (free) RAD001. These free levels of RAD001 are exceeded in serum from cancer patients receiving clinically beneficial daily regimens. In rodents, brain penetration of RAD001 was poor, but was dose-dependent and showed over-proportional uptake in rats with a longer t(1/2) compared to the systemic circulation.<br><br>CONCLUSIONS: The PK of RAD001 differed between mice and rats, with rats having a PK profile closer to that of humans. High intermittent doses of RAD001 may be more appropriate for treatment of brain tumors.}, }
@article {pmid19726581, year = {2009}, author = {MacConnachie, AA and Fox, R and Kennedy, DR and Seaton, RA}, title = {Faecal transplant for recurrent Clostridium difficile-associated diarrhoea: a UK case series.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {102}, number = {11}, pages = {781-784}, doi = {10.1093/qjmed/hcp118}, pmid = {19726581}, issn = {1460-2393}, mesh = {Aged ; Aged, 80 and over ; *Clostridioides difficile ; Diarrhea/epidemiology/microbiology/*therapy ; Enterocolitis, Pseudomembranous/epidemiology/microbiology/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Recurrence ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Clostridium difficile-associated diarrhoea (CDAD) is an increasingly common and life threatening consequence of modern medical practice. Recurrent disease is seen in up to one-third of patients and there is no consensus on optimal therapy. Restoration of normal colonic flora addresses the underlying pathogenic mechanism in CDAD.<br><br>METHODS: We describe the use of nasogastrically administered faecal transplant in the treatment of 15 patients with recurrent CDAD. Retrospective case note review was used to review the success and safety of therapy.<br><br>RESULTS: Of 15 patients treated using this technique, 11 were cured of CDAD. Two patients required a further course of metronidazole after transplantation and one patient required a second treatment. One patient had recurrence of CDAD 4 weeks after treatment following a course of broad-spectrum antibiotics. No adverse events were noted.<br><br>CONCLUSION: In our experience, this technique is an effective and safe treatment for recurrent CDAD. Faecal transplantation via a nasogastric tube could be considered in patients with refractory relapsing CDAD.}, }
@article {pmid19708892, year = {2010}, author = {Gruz, F and Fuxman, C and Errea, A and Tokumoto, M and Fernandez, A and Velasquez, J and Nagel, C and Ruf, A and Mauriño, E and Nachman, F and Rumbo, M and Gondolesi, G}, title = {Isospora belli infection after isolated intestinal transplant.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {12}, number = {1}, pages = {69-72}, doi = {10.1111/j.1399-3062.2009.00439.x}, pmid = {19708892}, issn = {1399-3062}, mesh = {Adult ; Animals ; Feces/parasitology ; Humans ; Intestine, Small/*transplantation ; Isospora/classification/*isolation &amp; purification ; Isosporiasis/diagnosis/*parasitology ; Male ; Young Adult ; }, abstract = {Isospora belli is a protozoan that only affects humans, after ingestion of Isospora's oocysts. Immunocompetent patients usually do not develop the infection. Immunocompromised hosts may have profuse diarrhea with other gastrointestinal symptoms. Treatment is based on trimethoprim-sulfamethoxazole. In 2006 we performed an isolated intestinal transplantation in a patient with ultra-short bowel syndrome. Neither rejection nor clinical problems occurred after transplant, but signs of intestinal inflammation were seen in every protocol biopsy starting at the first month post transplant. Almost 3 months after the procedure, the patient was re-admitted with diarrhea. I. belli infection was diagnosed by detection of the oocysts in stool samples. Antibiotic treatment with trimethoprim-sulfamethoxazole was initiated with excellent outcome and without relapses. To the best of our knowledge, this is the first case of isosporosis in a small bowel recipient.}, }
@article {pmid19705974, year = {2009}, author = {Roddie, C and Paul, JP and Benjamin, R and Gallimore, CI and Xerry, J and Gray, JJ and Peggs, KS and Morris, EC and Thomson, KJ and Ward, KN}, title = {Allogeneic hematopoietic stem cell transplantation and norovirus gastroenteritis: a previously unrecognized cause of morbidity.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {49}, number = {7}, pages = {1061-1068}, doi = {10.1086/605557}, pmid = {19705974}, issn = {1537-6591}, mesh = {Adolescent ; Adult ; Caliciviridae Infections/*epidemiology/virology ; Feces/virology ; Female ; Gastroenteritis/*epidemiology/virology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Norovirus/classification/genetics/*isolation &amp; purification ; RNA, Viral/genetics ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Sequence Analysis, DNA ; Transplantation, Homologous/*adverse effects ; Young Adult ; }, abstract = {BACKGROUND: A retrospective study of the clinical, epidemiologic, and virologic features of norovirus gastroenteritis in 12 adult allogeneic hematopoietic stem cell transplant (HSCT) recipients.<br><br>METHODS: Norovirus infection was diagnosed by reverse-transcriptase polymerase chain reaction. Strains were genotyped by nucleic acid sequence of the most highly conserved region of the norovirus gene encoding the capsid S (shell) domain.<br><br>RESULTS: Ten of 12 patients presented with vomiting of short duration, but diarrhea was present in all. The median time from onset to norovirus diagnosis was 1 month (range, 0.25-6.0 months). Eleven patients were receiving immunosuppression when norovirus infection was diagnosed: 8 for graft-versus-host disease (GVHD) in an organ other than gut, 1 for previous gut GVHD, and 2 for presumed gut GVHD that proved to be norovirus gastroenteritis. Six patients required enteral or parenteral nutrition for severe weight loss. In 10 patients, diarrhea lasted a median of 3 months (range, 0.5-14 months) and virus was shed at a high level throughout. The remaining 2 patients died after 4 months of diarrhea (one died of unrelated complications, and the other died of malnutrition). The noroviruses found were GII (untyped), GII-3, GII-4, and GII-7 in 1, 1, 9, and 1 patients, respectively. Eleven of the 12 patients had acquired their infection in the community. Phylogenetic analysis of the GII-4 strains demonstrated that all differed.<br><br>CONCLUSIONS: Noroviruses are a hitherto unsuspected cause of prolonged morbidity and mortality in adults after allogeneic HSCT. The use of reverse-transcriptase polymerase chain reaction to detect high viral load levels in feces distinguishes norovirus gastroenteritis from gut GVHD.}, }
@article {pmid19693296, year = {2009}, author = {Parera, VE and Koole, RH and Minderman, G and Edixhoven, A and Rossetti, MV and Batlle, A and de Rooij, FW}, title = {Novel null-allele mutations and genotype-phenotype correlation in Argentinean patients with erythropoietic protoporphyria.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {15}, number = {11-12}, pages = {425-431}, pmid = {19693296}, issn = {1528-3658}, mesh = {Adolescent ; Adult ; Alleles ; Argentina ; Child ; Child, Preschool ; DNA Mutational Analysis/*methods ; Family ; Female ; Ferrochelatase/*genetics ; Humans ; Male ; Middle Aged ; *Mutation ; Protoporphyria, Erythropoietic/*genetics ; }, abstract = {Erythropoietic protoporphyria (EPP) is an inherited disorder of porphyrin metabolism in which decreased activity of ferrochelatase (FECH) leads to accumulation of protoporphyrin IX (PP IX) in red blood cells, plasma, liver, and bile, and increased PP IX excretion in feces. Clinically, EPP is characterized by photosensitivity that begins in early childhood and includes burning, swelling, itching, and painful erythema in sun-exposed areas. Chronic liver disease is an important complication in a minority of EPP patients, and in some cases liver transplantation has been performed. So far, about 110 different mutations and several polymorphisms have been characterized in the human FECH gene. The relationship between mutations, polymorphisms, and porphyria development in Argentinean patients was investigated. This is the first genetic study carried out in the Argentinean population. In five Argentinean EPP families we detected three novel mutations: a deletion (451delT) producing a stop codon located 18 codons downstream from the mutation and two splicing mutations: IVS1-2A>G leading to exon 2 skipping and IVS4-2A>G, which causes the loss of the first 48 bp of exon 5. We also found two previously described mutations: C343T and 400delA, which produce stop codons. All patients had an FECH activity 25% of normal and also had the polymorphisms -251A>G in the promoter region and IVS1-23 C>T and IVS3-48 T>C. Our findings provide supporting evidence for the concept that the inheritance of the low expression allele IVS3-48C in trans with a mutation in the FECH gene is necessary for EPP to become clinically manifest.}, }
@article {pmid19690871, year = {2009}, author = {Saihara, R and Komuro, H and Urita, Y and Hagiwara, K and Kaneko, M}, title = {Myoblast transplantation to defecation muscles in a rat model: a possible treatment strategy for fecal incontinence after the repair of imperforate anus.}, journal = {Pediatric surgery international}, volume = {25}, number = {11}, pages = {981-986}, pmid = {19690871}, issn = {1437-9813}, mesh = {Animals ; Anus, Imperforate/*surgery ; Cells, Cultured ; Fecal Incontinence/*surgery ; Female ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Muscle, Skeletal/*surgery ; Myoblasts/*transplantation ; Rats ; Rats, Inbred F344 ; Rats, Sprague-Dawley ; }, abstract = {PURPOSE: Infants with higher anorectal anomalies often develop fecal incontinence after surgical reconstruction mainly due to the incomplete development of defecation muscles. We investigated the possibility of defecation muscle regeneration by myoblast transplantation to improve fecal continence.<br><br>METHODS: Myoblasts from F344 female rats at ages of 1 day, 1, 2, 3, 4, 8, and 12 weeks were prepared by a preplating method. In vivo muscle differentiation of myoblasts was evaluated using immunofluorescence after transplantation of GFP-positive myoblasts into nude mice, the damaged thigh muscles, and the levator ani muscle of GFP-negative rats.<br><br>RESULTS: The ratios of myoblasts obtained from 1 day, 1, 2, 3, 4, 8, and 12-week-old rats were 35, 71, 65, 61, 52, 44, and 23%, respectively. Myotube formation by transplanted myoblasts was observed in the back of nude mice. Myoblasts transplanted into damaged thigh muscles were integrated into recipient muscles with myofiber formation. Transferred myoblasts formed myotubes surrounding the levator ani muscle, although myofiber formation was not observed.<br><br>CONCLUSION: Myoblasts were most efficiently obtained from juvenile rats. Myoblast transplantation may provide a novel treatment strategy for improving fecal continence after repair of anorectal anomalies in infants.}, }
@article {pmid19667940, year = {2009}, author = {Rice, JP and Spier, BJ and Cornett, DD and Walker, AJ and Richie, K and Pfau, PR}, title = {Utility of colonoscopy in the evaluation of diarrhea in solid organ transplant recipients.}, journal = {Transplantation}, volume = {88}, number = {3}, pages = {374-379}, doi = {10.1097/TP.0b013e3181ae98ab}, pmid = {19667940}, issn = {1534-6080}, mesh = {Adolescent ; Adult ; Aged ; Algorithms ; Antiviral Agents/therapeutic use ; Biopsy ; Child ; Colon/*pathology ; *Colonoscopy ; Cytomegalovirus Infections/etiology/prevention &amp; control ; Diarrhea/*diagnosis/etiology/therapy ; Feces/microbiology/parasitology/virology ; Female ; Humans ; Male ; Middle Aged ; Organ Transplantation/*adverse effects ; Predictive Value of Tests ; Risk Factors ; Sensitivity and Specificity ; Young Adult ; }, abstract = {BACKGROUND: Diarrhea is common in solid organ transplant recipients. Colonoscopy with random biopsies is performed frequently in the diagnostic evaluation of the posttransplant population with diarrhea. The purpose of this study was to determine the sensitivity of colonoscopy with random biopsy in determining a specific diagnosis and changing management in solid organ transplant recipients with diarrhea.<br><br>METHODS: From October 1996 to June 2008, 88 patients were identified who had undergone solid organ transplantation and subsequently underwent colonoscopy for an indication of "diarrhea." These patient's electronic medical records were reviewed to determine patient demographics, laboratory results, findings on colonoscopy and histopathology, and any subsequent diagnoses made and management changes in relation to the diarrhea.<br><br>RESULTS: Eighty-eight patients (mean age 54 years, 65% male) underwent colonoscopy a mean of 69 months after transplantation. Abnormal colonoscopic findings were seen in 16 (18.2%) patients. Histopathology was abnormal in 17/80 (21.3%). However, only eight (9.1%) had findings on colonoscopy or pathologic condition that led to specific diagnosis being made. In addition, only nine (10.2%) patients had a change in medical management as a direct result of colonoscopy with biopsy.<br><br>CONCLUSION: Although colonoscopic or histopathologic abnormalities are common in the solid organ transplant recipient with diarrhea, the findings rarely lead to a specific diagnosis or management change. Colonoscopy with biopsy should be performed only after noninvasive testing for infectious diarrhea and a thorough review and adjustment of medications. In many patients, a trial of antidiarrheal medication is warranted before colonoscopy.}, }
@article {pmid19663233, year = {2009}, author = {Kuroda, T}, title = {[Continuing problems in patients who undergo repair for anorectal malformation].}, journal = {Nihon Geka Gakkai zasshi}, volume = {110}, number = {4}, pages = {191-194}, pmid = {19663233}, issn = {0301-4894}, mesh = {Adult ; Anal Canal/*abnormalities/surgery ; Female ; Humans ; Male ; Postoperative Complications ; Pregnancy ; Rectum/*abnormalities/surgery ; Sexual Dysfunction, Physiological/etiology ; Urologic Diseases/etiology ; }, abstract = {As the number of long-term survivors after the repair of anorectal malformations increases, continuing problems affecting the quality of adult life are receiving greater attention in the field of pediatric surgery. Many studies concluded that completely normal defecation could not be achieved after surgical repair of high-type anomalies, even though function improved with age. Reports of the long-term outcomes of surgical procedures to restore anal sphincter function, such as gracilis muscle transplantation, remained limited. Urinary complications such as neurogenic bladder are frequently observed in adulthood among patients born with anorectal malformations. Urinary and fecal incontinence disrupt job performance and other social activities in most patients. In addition, a fairly high incidence of retrograde ejaculation and abnormal penile erection causing female infertility has been reported recently, although successful management of pregnancy and delivery was reported in selected cases. Interdisciplinary medical support is necessary to treat these problems in adulthood after the repair of anorectal malformations and should be established as a future goal.}, }
@article {pmid19647239, year = {2009}, author = {Pasricha, PJ and Ahmed, I and Jankowski, RJ and Micci, MA}, title = {Endoscopic injection of skeletal muscle-derived cells augments gut smooth muscle sphincter function: implications for a novel therapeutic approach.}, journal = {Gastrointestinal endoscopy}, volume = {70}, number = {6}, pages = {1231-1237}, doi = {10.1016/j.gie.2009.05.014}, pmid = {19647239}, issn = {1097-6779}, mesh = {Animals ; Cell Differentiation ; Cell Transplantation/*methods ; Dogs ; Endoscopy, Gastrointestinal ; Fluorescent Antibody Technique ; Male ; Muscle, Skeletal/*cytology ; Pylorus/*physiology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {INTRODUCTION: Sphincter function is a common problem in gastroenterology and leads to disorders such as GERD and fecal incontinence.<br><br>OBJECTIVE: We hypothesized that transplantation of skeletal muscle-derived cells (MDCs) into GI sphincters may improve their function, leading to a more physiological approach to treating these disorders.<br><br>DESIGN: We performed experiments to test the potential of MDCs to survive and differentiate within the GI smooth muscle in order to gain further knowledge on the biology of skeletal muscle transplantation in GI smooth muscle sphincters as well as to test the safety and feasibility of endoscopic injection of MDCs in a large animal model.<br><br>SETTING: Animal laboratory.<br><br>INTERVENTIONS: Adult male Sprague-Dawley rats and adult male beagle dogs were used. Rat-derived and dog-derived MDCs were prepared in vitro and labeled with DiI. DiI-labeled, rat-derived MDCs (200,000/4 muL phosphate buffered saline solution) were injected bilaterally in the pyloric wall of rats, and survival, differentiation, and in vitro contractility were assessed 1 month after transplantation. Dog-derived MDCs (4.0 x 10(6) cells) were also injected into the lower esophageal sphincter of 3 beagle dogs by using a standard variceal sclerotherapy needle after baseline esophageal manometry and pH monitoring. The dogs were treated with daily cyclosporine, and 2 weeks later esophageal manometry was repeated and the esophagus was examined histologically. Differentiation of grafted cells was assessed by immunofluorescence, using specific antibodies to markers of the smooth muscle phenotype (smooth muscle actin) and of the skeletal muscle phenotype (skeletal muscle myosin).<br><br>RESULTS: In rats, grafted MDCs were visualized based on DiI fluorescence and were found to be localized within the muscle wall and in the muscularis mucosa. In vitro organ bath studies showed a significant increase in the contractile response of the pyloric sphincter to exogenous acetylcholine. In dogs, MDC injection resulted in a significant increase in baseline lower esophageal sphincter pressure. Further, in 1 dog with significant baseline acid reflux, MDC injection resulted in a reduction of acid reflux, with the fraction of time with pH <4 decreasing from 26.5% to 1.5%. Transplanted MDCs were seen adding bulk to the lower esophageal area and were well-integrated into the surrounding tissue. Immunofluorescence analysis revealed weak expression of skeletal muscle myosin in grafted MDCs and no expression of smooth muscle actin in either rats or dogs.<br><br>LIMITATIONS: Animal study.<br><br>CONCLUSION: MDCs can survive and integrate into GI smooth muscle and augment their contractile response. Thus, they may have potential for the treatment of a variety of conditions.}, }
@article {pmid19644323, year = {2009}, author = {Verhelst, L and Ackerman, P and Van Meirhaeghe, J}, title = {Traumatic posterior lumbosacral spondyloptosis in a six-year-old: a case report and review of the literature.}, journal = {Spine}, volume = {34}, number = {17}, pages = {E629-34}, doi = {10.1097/BRS.0b013e3181aa2e1a}, pmid = {19644323}, issn = {1528-1159}, mesh = {Accidents, Traffic ; Bone Transplantation ; Child ; Decompression, Surgical ; Fecal Incontinence/etiology/physiopathology ; Humans ; Internal Fixators ; Joint Dislocations/*complications/diagnostic imaging/pathology ; Lumbar Vertebrae/diagnostic imaging/*injuries/pathology ; Male ; Paraplegia/etiology/pathology/physiopathology ; Polyradiculopathy/diagnostic imaging/*etiology/pathology ; Radiography ; Plastic Surgery Procedures ; Sacrum/diagnostic imaging/*injuries/pathology ; Spinal Canal/diagnostic imaging/injuries/pathology ; Spinal Fractures/*complications/diagnostic imaging/pathology ; Spinal Fusion ; Spinal Nerve Roots/injuries/pathology/physiopathology ; Treatment Outcome ; Urinary Bladder, Neurogenic/etiology/physiopathology ; Wounds and Injuries/*complications/diagnostic imaging/pathology ; }, abstract = {STUDY DESIGN: Report of a traumatic posterior lumbosacral spondyloptosis in a 6-year-old.<br><br>OBJECTIVES: To describe this type of fracture-dislocation in children. To evaluate a possible trauma mechanism. To evaluate specific characteristics of this type of lesion in children.<br><br>SUMMARY OF BACKGROUND DATA: Fractures of the lumbar spine in children are rare. They are without exception caused by high-energy trauma. Fracture-dislocations mostly occur in the anterior direction. There are several reports of traumatic retrolisthesis in adults. To our knowledge, this is the first report of a retrolisthesis at the lumbosacral junction in a child.<br><br>METHODS: While sitting, a 6-year-old boy was hit by a truck. He presented with a flaccid paraparesis below L3. Radiologic investigations showed a posterior spondyloptosis at L5-S1. He was treated by open reduction with a pediatric posterior spinal instrumentation and posterolateral grafting.<br><br>RESULTS: After 1 year, the patient showed good radiologic fracture reduction and graft incorporation. There was no pain in the lumbar area. There was still a complete neurologic deficit beneath the L3 level, with loss of bladder and anal sphincter function. The patient was entered into a children's rehabilitation program 5 weeks after surgery and is continuously improving his overall functional level.<br><br>CONCLUSION: Traumatic retrolisthesis of the lumbosacral spine is extremely rare, especially in children. We believe shear force while sitting is the key traumatic factor. We believe a simple posterior fusion with posterolateral grafting is sufficient to stabilize the spine in children. Extensive soft tissue damage causes an elevated risk of infection. Because of root avulsion, the level of paralysis can be several levels higher than the level of dislocation.}, }
@article {pmid19639018, year = {2009}, author = {Zuber, J and Bellanné-Chantelot, C and Carette, C and Canaud, G and Gobrecht, S and Gaha, K and Mallet, V and Martinez, F and Thervet, E and Timsit, J and Legendre, C and Dubois-Laforgue, D}, title = {HNF1B-related diabetes triggered by renal transplantation.}, journal = {Nature reviews. Nephrology}, volume = {5}, number = {8}, pages = {480-484}, pmid = {19639018}, issn = {1759-507X}, mesh = {Adult ; Cholestasis/immunology ; Diabetes Mellitus, Type 2/diagnosis/*genetics/immunology ; Diagnosis, Differential ; Frameshift Mutation ; Hepatocyte Nuclear Factor 1-beta/*genetics ; Humans ; Immunosuppressive Agents/therapeutic use ; *Kidney Transplantation/immunology ; Male ; Pruritus/immunology ; }, abstract = {BACKGROUND: A 37-year-old man developed cholestasis-associated pruritus followed by overt hyperglycemia (blood glucose level 23 mmol/l), necessitating insulin treatment, within weeks of undergoing renal transplantation. He had a history of gout, but his fasting blood glucose and glycated hemoglobin concentrations had been normal before transplantation.<br><br>INVESTIGATIONS: Physical examination; laboratory tests, including assessment of glycated hemoglobin, anti-glutamic-acid-decarboxylase and anti-islet-antigen-2 antibodies, liver enzymes, renal function, tacrolimus blood trough level, exocrine (fecal elastase) and endocrine (C-peptide) pancreatic function; abdominal CT scan; liver biopsy; and screening of the hepatocyte nuclear factor 1 homeobox B (transcription factor 2) gene, HNF1B.<br><br>DIAGNOSIS: New-onset diabetes after transplantation associated with a newly described deletion in HNF1B.<br><br>MANAGEMENT: Minimization of tacrolimus exposure and withdrawal of steroids considerably reduced the patient's insulin requirement, and cholestasis-related pruritus was dramatically improved by administration of ursodeoxycholic acid. Renal ultrasonography and screening for the HNF1B molecular abnormality were offered to the patient's relatives.}, }
@article {pmid19637789, year = {2009}, author = {Hellemans, R and Naegels, S and Holvoet, J}, title = {Fecal transplantation for recurrent Clostridium difficile colitis, an underused treatment modality.}, journal = {Acta gastro-enterologica Belgica}, volume = {72}, number = {2}, pages = {269-270}, pmid = {19637789}, issn = {1784-3227}, mesh = {*Clostridioides difficile ; Colitis/*therapy ; Feces/*microbiology ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Transplantation, Homologous/methods ; }, }
@article {pmid19626610, year = {2009}, author = {Babakir-Mina, M and Ciccozzi, M and Alteri, C and Polchi, P and Picardi, A and Greco, F and Lucarelli, G and Arcese, W and Perno, CF and Ciotti, M}, title = {Excretion of the novel polyomaviruses KI and WU in the stool of patients with hematological disorders.}, journal = {Journal of medical virology}, volume = {81}, number = {9}, pages = {1668-1673}, doi = {10.1002/jmv.21559}, pmid = {19626610}, issn = {1096-9071}, mesh = {Adenoviridae/isolation &amp; purification ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Cluster Analysis ; Cytomegalovirus/isolation &amp; purification ; DNA, Viral/chemistry/genetics ; Feces/*virology ; Female ; Hematologic Neoplasms/*complications/*drug therapy ; Humans ; Immunocompromised Host ; Infant ; Male ; Middle Aged ; Molecular Sequence Data ; Phylogeny ; Polyomavirus/classification/genetics/*isolation &amp; purification ; Polyomavirus Infections/*virology ; Sequence Analysis, DNA ; Young Adult ; }, abstract = {Infection with human polyomaviruses BKV and JCV is asymptomatic, and lifelong and widespread, among the general population. However, in the setting of immunosuppression, secondary to medications or viral infection, for example, with HIV, reactivation can occur and result in severe disease. In this study, stool specimens from 31 patients with hematological disorders (25 transplanted and 6 non-transplanted) were examined prospectively to determine whether the novel polyomaviruses KIV and WUV reactivated and were excreted in the gastrointestinal tract. Reactivation was correlated with the appearance of gastrointestinal and respiratory symptoms. Of the 31 patients examined, KIV and WUV were detected in 13 transplanted patients as single infection or in combination with BKV, cytomegalovirus (CMV), and adenovirus (Adv). Because of frequent co-infections, a clear correlation between novel polyomaviruses and clinical symptoms could not be established. There was no correlation between demographic variables and detection of KIV and WUV. Phylogenetic analysis of the small t-antigen gene of KIV and WUV isolates showed that the novel polyomaviruses identified in feces clustered with those identified in the respiratory tract suggesting an oral-fecal transmission of these viruses. The novel polyomaviruses KI and WU may have a pathogenic role in immunocompromised patients.}, }
@article {pmid19625473, year = {2009}, author = {Henke-Gendo, C and Harste, G and Juergens-Saathoff, B and Mattner, F and Deppe, H and Heim, A}, title = {New real-time PCR detects prolonged norovirus excretion in highly immunosuppressed patients and children.}, journal = {Journal of clinical microbiology}, volume = {47}, number = {9}, pages = {2855-2862}, pmid = {19625473}, issn = {1098-660X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Base Sequence ; Caliciviridae Infections/*diagnosis/virology ; Child ; Child, Preschool ; DNA Primers ; Feces/virology ; Female ; Humans ; Immunocompromised Host ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Molecular Sequence Data ; Norovirus/genetics/*isolation &amp; purification ; Phylogeny ; Polymerase Chain Reaction/*methods ; RNA, Viral/genetics ; Retrospective Studies ; Sensitivity and Specificity ; Sequence Alignment ; Sequence Analysis, DNA ; Virus Shedding ; Young Adult ; }, abstract = {Noroviruses (NoV) are a major cause of epidemic nonbacterial gastroenteritis and affect all age groups worldwide. Three of five NoV genogroups, namely, genogroup I (GI), GII, and GIV, are associated with human disease. Unfortunately, these genogroups demonstrate a high degree of sequence diversity, complicating the design of pan-NoV diagnostic PCR tests. To decrease the risk of false-negative test results, we have developed a new one-step real-time TaqMan reverse transcription-PCR protocol. This protocol detects all human NoV genogroups in one reaction with a sensitivity of 400 virus genome equivalents/reaction for both GI and GII. The use of in vitro-transcribed NoV RNA as an external standard allows (semi)quantification of viral loads in samples. In a retrospective analysis of 206 stool samples from 77 patient episodes, the duration of NoV excretion and the amount of virus excreted were determined. Twenty (26.0%) of these episodes lasted longer than 10 days. Univariate risk factor analysis revealed the patient status after organ transplantation (odds ratio [OR], 7.49 [95% confidence interval, 2.06 to 28.32]; P < 0.001), immunosuppression (OR, 9.19 [95% confidence interval, 2.50 to 35.39]; P < 0.001), and age of less than 10 years (OR, 4.58 [95% confidence interval, 1.36 to 15.77]; P = 0.004) as risk factors for a NoV excretion period of more than 10 days. These findings were confirmed by time-dependent Kaplan-Meier analyses, whereas multivariate Cox regression analyses identified immunosuppression as the sole risk factor. Surprisingly, in contrast to the excretion periods, the viral loads in stools did not increase in connection with age or immunosuppressive status. This fact may be one important piece in the pattern of high-level NoV transmissibility and may have an impact on the development of transmission prevention strategies.}, }
@article {pmid19622969, year = {2009}, author = {Shobeiri, SA and Chimpiri, AR and Allen, A and Nihira, MA and Quiroz, LH}, title = {Surgical reconstitution of a unilaterally avulsed symptomatic puborectalis muscle using autologous fascia lata.}, journal = {Obstetrics and gynecology}, volume = {114}, number = {2 Pt 2}, pages = {480-482}, doi = {10.1097/AOG.0b013e3181ae6ad6}, pmid = {19622969}, issn = {0029-7844}, mesh = {Dyspareunia/diagnosis/etiology/*surgery ; Fascia Lata/*transplantation ; Fecal Incontinence/diagnosis/etiology/*surgery ; Female ; Humans ; Muscle, Skeletal/pathology/*surgery ; Obstetric Labor Complications/diagnosis/etiology/surgery ; Pelvic Floor/pathology/*surgery ; Pregnancy ; Puerperal Disorders/diagnosis/etiology/*surgery ; }, abstract = {BACKGROUND: The puborectalis muscle is an important muscle for the maintenance of fecal continence. We present a novel surgical technique for repair of symptomatic avulsed puborectalis muscle.<br><br>CASE: This woman presented with dyspareunia and fecal incontinence since the vaginal birth of her child 2 years before. The diagnosis of an avulsed right puborectalis was made by physical examination and confirmed by magnetic resonance imaging and three-dimensional ultrasonography. Fascia lata was harvested from the patient's thigh and used to reconstitute the missing portion of the puborectalis muscle. At 12 months postoperatively, the patient was continent of stool and relieved of dyspareunia.<br><br>CONCLUSION: The patient's dyspareunia and fecal incontinence were alleviated by restoring normal anatomy.}, }
@article {pmid19303571, year = {2009}, author = {Bauer, MP and van Dissel, JT}, title = {Alternative strategies for Clostridium difficile infection.}, journal = {International journal of antimicrobial agents}, volume = {33 Suppl 1}, number = {}, pages = {S51-6}, doi = {10.1016/S0924-8579(09)70018-4}, pmid = {19303571}, issn = {1872-7913}, mesh = {*Antibiosis ; Clostridioides difficile/*growth &amp; development/immunology ; Enterocolitis, Pseudomembranous/*prevention &amp; control/*therapy ; Humans ; Immunotherapy/methods ; Probiotics/therapeutic use ; Randomized Controlled Trials as Topic ; }, abstract = {Although antibiotics are generally effective in achieving symptomatic recovery from Clostridium difficile infection, the disease frequently relapses, partly because antibiotics not only kill C. difficile, but also disrupt colonisation resistance of the gut microflora. Non-antibiotic strategies for the prevention and treatment of the infection include probiotics, deliberate colonisation by non-toxigenic C. difficile strains, toxin-binding agents, active immunisation, passive immunotherapy with intravenous immunoglobulin, monoclonal antibodies or bovine anti-C. difficile whey concentrate, and faecal transplantation. None of these alternative therapies has proven benefit in therapy or prevention, and prospective randomised trials are urgently needed.}, }
@article {pmid19586515, year = {2009}, author = {Vassallo, C and Brazzelli, V and Zecca, M and Locatelli, F and Alessandrino, PE and Borroni, G}, title = {Isomorphic cutaneous graft-versus-host disease reaction after ultraviolet exposure: clinical, histological and direct immunofluorescence studies of four allo-transplanted patients.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {23}, number = {8}, pages = {913-918}, doi = {10.1111/j.1468-3083.2009.03220.x}, pmid = {19586515}, issn = {1468-3083}, mesh = {Child ; Child, Preschool ; Disease Progression ; Female ; Fluorescent Antibody Technique, Direct ; Graft vs Host Disease/*etiology/immunology/*pathology ; Hematologic Diseases/surgery ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Keratinocytes/immunology/pathology ; Lymphocytes/immunology/pathology ; Male ; Middle Aged ; Radiodermatitis/*etiology/immunology/*pathology ; Transplantation, Homologous ; Ultraviolet Rays/*adverse effects ; }, abstract = {BACKGROUND: Acute and chronic graft-versus-host disease (GVHD) continues to be a major limitation to successful haematopoietic stem cell transplantation. If experimental studies and clinical observations could partially elucidate the pathophysiology of acute GVHD, the biology of chronic GVHD is still much less well understood.<br><br>OBJECTIVES: The aim of this study is to describe a peculiar photoinduced rash which triggered acute and then chronic lesions of GVHD in four allogenic haematopoietic-transplanted patients and discuss the possible aetiology and treatment.<br><br>PATIENTS/METHODS: Four patients, two children and two adults affected by either mild or severe chronic GVHD, developed an erythematous rash on sun- or narrow-band ultraviolet B-exposed area, which triggered the onset of acute lesions of GVHD. Any of the patients presented neither a history of photosensitivity nor circulating autoantibodies nor urinary/fecal porphyrine.<br><br>RESULTS: The histopathologic findings were characterized by an interface dermatitis with sparse perivascular infiltrate of lymphocytes and scattered necrotic keratinocytes, especially in the upper part of epidermis. Direct immunofluorescence studies excluded lupus-like pattern, revealing nests of fluorescent bodies at the dermal-epidermal junction and in papillary dermis.<br><br>CONCLUSIONS: This peculiar isomorphic reaction of cutaneous GVHD after sun or narrow-band ultraviolet B exposures is described, and the possible mechanism involved is discussed. It may represent an interesting model of progression of chronic GVHD, starting with an acute stage and ending up with chronic clinical and histological findings, especially considering that there is no animal model that fully replicates all of the features of chronic GVHD in humans.}, }
@article {pmid19585093, year = {2009}, author = {Schanz, J and Weiss, B and Henrich, D and Bohrer, MH and Uppenkamp, M}, title = {[30 year-old patient with multiple pelvic lesions and fecal incontinence].}, journal = {Der Internist}, volume = {50}, number = {9}, pages = {1155, 1157-60}, pmid = {19585093}, issn = {1432-1289}, mesh = {Adult ; Fecal Incontinence/diagnosis/etiology/*prevention &amp; control ; Humans ; Leukemia, Myeloid, Acute/complications/*diagnosis/*surgery ; Male ; Pelvic Neoplasms/complications/*diagnosis/*surgery ; *Stem Cell Transplantation ; Treatment Outcome ; }, abstract = {In a 30 year-old patient with subacute loss of bowel control and perianal anesthesia radiologic examination showed multiple bone lesions. The results of a bone marrow aspiration showed acute myeloid leukemia M2 with translocation t(8,21) associated with granulocytic sarcoma. The patient was treated with high dose chemotherapy and had a complete remission after autologous stem cell transplantation.}, }
@article {pmid19558344, year = {2009}, author = {Ranganathan, N and Friedman, EA and Tam, P and Rao, V and Ranganathan, P and Dheer, R}, title = {Probiotic dietary supplementation in patients with stage 3 and 4 chronic kidney disease: a 6-month pilot scale trial in Canada.}, journal = {Current medical research and opinion}, volume = {25}, number = {8}, pages = {1919-1930}, doi = {10.1185/03007990903069249}, pmid = {19558344}, issn = {1473-4877}, mesh = {Adult ; Aged ; Double-Blind Method ; Female ; Humans ; Kidney Failure, Chronic/classification/*therapy ; Male ; Middle Aged ; Ontario ; Outcome Assessment, Health Care/methods ; Pilot Projects ; Probiotics/administration &amp; dosage/*therapeutic use ; Prospective Studies ; }, abstract = {AIM: This was a pilot clinical trial to assess biochemical and clinical effects of an oral probiotic dietary supplement in chronic kidney disease (CKD) patients (stages 3 and 4).<br><br>METHODS: A prospective, randomized, double-blind, crossover, placebo-controlled, 6-month trial of probiotic bacteria was conducted in 16 outpatients in Ontario, Canada. Primary endpoints included effect on hematologic, biochemical, and fecal variables, and on general well-being as assessed by quality of life (QOL). These outcomes were evaluated from biochemical parameters, mainly blood urea nitrogen (BUN), creatinine, uric acid, and C-reactive protein (CRP) as a general inflammatory marker. QOL was assessed on a subjective scale of 1 to 10 as the secondary parameter.<br><br>TRIAL REGISTRATION: This pilot study forms part of registered trial NCT00760162.<br><br>RESULTS: A total of 13 patients completed the study. Three patients dropped out: one was the receiver of a transplant. The second dropped out for unknown reasons and the third died of myocardial infarction (unrelated to probiotic bacteria or the protocol). Among the 13 patients who completed the trial, the mean change in BUN concentration during the probiotic treatment period (-2.93 mmol/L) differed significantly (p = 0.002) from the mean change in BUN concentration during the placebo period (4.52 mmol/L). In addition, the mean changes in uric acid concentration were moderate during the KB period (24.70 micromol/L) versus during the placebo period (50.62 micromol/L, p = 0.050), and the changes in serum creatinine concentration were insignificant. Neither gastrointestinal nor infectious complications were noted in any subject with improved QOL.<br><br>CONCLUSION: Orally administered probiotic bacteria selected to metabolize nitrogenous wastes may be tolerated for as long as 6 months. A major limitation of this trial is its small size that may have precluded detection of changes in other biochemical or hematologic parameters that would be evident in larger cohorts. Extension of the evaluation of this probiotic bacterial mixture will include a dose escalation trial in a similar prospective, placebo-controlled, and double-blind study site.}, }
@article {pmid19536987, year = {2009}, author = {Privitera, AC and Oliveri, CE and Randazzo, G and Ohazuruike, NL and Prumeri, S and Politi, A and Succi, L}, title = {Biofeedback therapy for faecal incontinence: our experience.}, journal = {Chirurgia italiana}, volume = {61}, number = {2}, pages = {149-154}, pmid = {19536987}, issn = {0009-4773}, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Biofeedback, Psychology/*methods ; Electric Stimulation Therapy/*methods ; Electromyography ; Fecal Incontinence/*therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Patient Satisfaction ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {Biofeedback combined with electrical stimulation is an appealing conservative therapeutic option in patients with faecal incontinence. A total of 51 patients with faecal incontinence referred to our proctological division from March 2004 to June 2008 were studied. All patients were treated with biofeedback plus electrical stimulation. All patients underwent, on average, twice-weekly 15-minute electromyography-biofeedback training sessions followed by 5 minutes of electrical stimulation. Patients satisfaction, physiological data, clinical symptoms and a modified Wexner score were used to assess improvement. At 6 months' follow-up, nearly all physiological parameters showed a significant improvement (p < 0.05) and there was a reduction in the loss of solid stool (from 78.4 to 27.5 percent), in the loss of liquid stool (from 100 to 29.4 percent), and in pad usage (from 74.5 to 17.6 percent). At 1-year follow-up, an improvement in satisfaction was reported by 41/51 of patients (80.4%). This study suggests that biofeedback plus electrical stimulation leads to a substantial improvement in faecal incontinence symptoms and underlines the importance of anorectal functional tests to examine and guide the management of patients with faecal incontinence.}, }
@article {pmid19508489, year = {2009}, author = {Dobrowolski, S and Hać, S and Kobiela, J and Sledziński, Z}, title = {Should we preserve the inferior mesenteric artery during sigmoid colectomy?.}, journal = {Neurogastroenterology and motility}, volume = {21}, number = {12}, pages = {1288-e123}, doi = {10.1111/j.1365-2982.2009.01331.x}, pmid = {19508489}, issn = {1365-2982}, mesh = {Adult ; Aged ; *Colectomy ; Colon, Sigmoid/*surgery ; Constipation/epidemiology ; Defecation/physiology ; Fecal Incontinence/etiology ; Female ; Follow-Up Studies ; Humans ; Ligation ; Male ; Mesenteric Artery, Inferior/*surgery ; Middle Aged ; Prospective Studies ; Rectum/surgery ; Surgical Procedures, Operative ; Surveys and Questionnaires ; }, abstract = {Ligation of the inferior mesenteric artery (IMA) during sigmoid colectomy may cause sympathetic denervation of the rectal stump. The purpose of our study was to investigate the functional results after sigmoid resection following ligation or preservation of the IMA. We prospectively analysed 44 patients (21 female and 23 male, mean age 60.6 +/- 11.79 years) with sigmoid tumour. Sigmoid colectomy with preservation of the IMA was performed in 21 patients, and ligation of the IMA with sigmoidectomy was carried out in 23 patients. Bowel function follow-up was performed by use of questionnaires: standardized functional questionnaire, constipation-specific, and incontinence scales before, 6 and 12 months after surgery. The quality of life was measured by means of the Fecal Incontinence Quality of Life (FIQL) scale. After sigmoid colectomy with division of the IMA, patients presented with a higher rate of fecal incontinence and increased stool frequency compared with patients after sigmoid resection with preservation of the IMA. Deterioration of FIQL was also observed in patients with ligated IMA. Preservation of the IMA during sigmoid colectomy in selected patients lowers the frequency of postoperative impaired anorectal function.}, }
@article {pmid19486428, year = {2009}, author = {Roslev, P and Iversen, L and Sønderbo, HL and Iversen, N and Bastholm, S}, title = {Uptake and persistence of human associated Enterococcus in the mussel Mytilus edulis: relevance for faecal pollution source tracking.}, journal = {Journal of applied microbiology}, volume = {107}, number = {3}, pages = {944-953}, doi = {10.1111/j.1365-2672.2009.04272.x}, pmid = {19486428}, issn = {1365-2672}, mesh = {Animals ; Carrier Proteins/genetics ; Colony Count, Microbial ; Enterococcus ; Enterococcus faecalis/genetics/growth &amp; development/*isolation &amp; purification ; Enterococcus faecium/genetics/growth &amp; development/*isolation &amp; purification ; Environmental Monitoring/*methods ; Feces/*microbiology ; Genetic Markers ; Humans ; Mytilus edulis/*microbiology ; Polymerase Chain Reaction ; Seawater/*microbiology ; Seminal Plasma Proteins/genetics ; Water Microbiology ; }, abstract = {AIMS: Micro-organisms and molecular markers for microbial source tracking (MST) in coastal waters are often present at low numbers, and often exhibit significant variability in time and space. In this study, we investigated the uptake, accumulation, and persistence of human associated Enterococcus in the mussel Mytilus edulis.<br><br>METHODS AND RESULTS: The human associated molecular markers esp in Enterococcus faecium, and M66 in Enterococcus faecalis were targetted by PCR in seawater and mussel samples from coastal sites affected by sewage contamination. Both native mussels and mussels transplanted from pristine to polluted sites were included. The results showed that the esp and M66 markers were often not detectable in seawater whereas mussels were enriched in the markers. Human associated E. faecalis accumulated rapidly in M. edulis, and reached maximum levels after 4-6 h with concentration 30-300 times greater than in the surrounding seawater. Enterococcus faecalis retained in M. edulis showed a survival comparable to planktonic E. faecalis in seawater with half lives of 30 and 22 h, respectively. Human associated markers remained detectable for 120 h in M. edulis after faecal contamination.<br><br>CONCLUSIONS: The study demonstrated that native and transplanted M. edulis can accumulate and retain human associated molecular markers relevant for MST.<br><br>Mussels should be considered as additional targets in MST studies in coastal waters.}, }
@article {pmid19462212, year = {2009}, author = {Morton, JR and Ansari, N and Glanville, AR and Meagher, AP and Lord, RV}, title = {Distal intestinal obstruction syndrome (DIOS) in patients with cystic fibrosis after lung transplantation.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {13}, number = {8}, pages = {1448-1453}, pmid = {19462212}, issn = {1873-4626}, mesh = {Adolescent ; Adult ; Cystic Fibrosis/*surgery ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Ileal Diseases/diagnostic imaging/*etiology/surgery ; *Ileocecal Valve ; Intestinal Obstruction/diagnostic imaging/*etiology/surgery ; Laparotomy ; Lung Transplantation/*adverse effects ; Male ; Middle Aged ; Prognosis ; Radiography, Abdominal ; Retrospective Studies ; Syndrome ; Time Factors ; Tomography, X-Ray Computed ; Young Adult ; }, abstract = {BACKGROUND: Cystic fibrosis (CF) is the commonest inherited life-threatening disease in Caucasians. With increased longevity, more patients with CF are developing gastrointestinal complications including the distal intestinal obstruction syndrome (DIOS), in which ileocecal obstruction is caused by viscid mucofeculent material. The optimal management of DIOS is uncertain.<br><br>METHODS: The medical records of all patients with CF who underwent lung transplantation at this institution during a 15-year period were reviewed. The definition of DIOS required the presence of both clinical and radiological features of ileocecal obstruction.<br><br>RESULTS: One hundred twenty-one patients with CF underwent lung transplantation during the study period. During a minimum 2-year follow-up, there were 17 episodes of DIOS in 13 (10.7%) patients. The development of DIOS was significantly associated with a past history of meconium ileus (odds ratio 20.7, 95% C.I. 5.09-83.9) or previous laparotomy (odds ratio 4.93, 95% C.I. 1.47-16.6). All six patients who developed DIOS during the transplantation admission had meconium ileus during infancy, and five had undergone pretransplant laparotomy for CF complications. First-line treatment for all patients was a combination of medication (laxatives, stool softeners, and bowel preparation formulas). This was successful in 14 of the 17 DIOS but needed to be given for up to 14 days. The other three patients required laparotomy with enterotomy and fecal disimpaction. This provided definitive resolution of DIOS except in one patient who presented late and died despite ileal decompression and ileostomy.<br><br>CONCLUSIONS: DIOS occurred in approximately 10% of CF patients after lung transplantation. Patients with a history of meconium ileus or previous laparotomy are at high risk of developing DIOS. Patients with DIOS require early aggressive management with timely laparotomy with enterotomy and possible stoma formation when non-operative therapy is unsuccessful.}, }
@article {pmid19454652, year = {2009}, author = {Davé, SH and Tilstra, JS and Matsuoka, K and Li, F and DeMarco, RA and Beer-Stolz, D and Sepulveda, AR and Fink, MP and Lotze, MT and Plevy, SE}, title = {Ethyl pyruvate decreases HMGB1 release and ameliorates murine colitis.}, journal = {Journal of leukocyte biology}, volume = {86}, number = {3}, pages = {633-643}, pmid = {19454652}, issn = {1938-3673}, support = {R01 DK054452-09/DK/NIDDK NIH HHS/United States ; F30 ES013617/ES/NIEHS NIH HHS/United States ; 1 P01 CA 101944/CA/NCI NIH HHS/United States ; R01 DK054452/DK/NIDDK NIH HHS/United States ; P30 DK34987/DK/NIDDK NIH HHS/United States ; 2 R01 DK54452/DK/NIDDK NIH HHS/United States ; }, mesh = {Adenocarcinoma/metabolism/pathology/secondary ; Animals ; Annexin A5/metabolism ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Colitis/chemically induced/*metabolism/pathology ; Colonic Neoplasms/metabolism/pathology/secondary ; Cytokines/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Fluorescein-5-isothiocyanate/metabolism ; HMGB1 Protein/*metabolism ; In Situ Nick-End Labeling ; Interleukin-10/deficiency/genetics ; Interleukin-12 Subunit p40/metabolism ; Intestinal Mucosa/metabolism ; Liver Neoplasms/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microtubule-Associated Proteins/metabolism ; Neoplasm Metastasis ; Neoplasm Transplantation ; Nitric Oxide/metabolism ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases/metabolism ; Pyruvates/*metabolism/pharmacology ; Random Allocation ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic/metabolism ; Transfection ; }, abstract = {Signals from stressed cells and the enteric microbiota activate macrophages and dendritic cells and mediate intestinal inflammation. HMGB1 serves as an immunogenic stimuli causing release of inflammatory cytokines by myeloid cells. Ethyl pyruvate inhibits secretion of HMGB1 and improves survival in models of endotoxemia and hemorrhagic shock. We reasoned that ethyl pyruvate may be protective in colitis, which involves similar inflammatory pathways. In IL-10(-/-) mice with established chronic colitis, ethyl pyruvate administration ameliorated colitis and reduced intestinal cytokine production. IL-10(-/-) mice demonstrated increased intestinal HMGB1 expression and decreased expression of RAGE compared with wild-type mice. Fecal HMGB1 levels were decreased in ethyl pyruvate-treated mice. Furthermore, ethyl pyruvate induced HO-1 expression in intestinal tissue. In TNBS-induced colitis, intrarectal administration of ethyl pyruvate resulted in amelioration of colitis and reduced intestinal cytokine production. In LPS-activated murine macrophages, ethyl pyruvate decreased expression of IL-12 p40 and NO production but did not affect IL-10 levels. Ethyl pyruvate did not inhibit nuclear translocation of NF-kappaB family members but attenuated NF-kappaB DNA binding. Additionally, ethyl pyruvate induced HO-1 mRNA and protein expression and HO-1 promoter activation. Moreover, ethyl pyruvate prevented nuclear-to-cytoplasmic translocation of HMGB1. In conclusion, the HMGB1/RAGE pathway has pathophysiologic and diagnostic significance in experimental colitis. Ethyl pyruvate and other strategies to inhibit HMGB1 release and function represent promising interventions in chronic inflammatory diseases.}, }
@article {pmid19432824, year = {2009}, author = {Huttunen, P and Lappalainen, M and Salo, E and Lönnqvist, T and Jokela, P and Hyypiä, T and Peltola, H}, title = {Differential diagnosis of acute central nervous system infections in children using modern microbiological methods.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {98}, number = {8}, pages = {1300-1306}, doi = {10.1111/j.1651-2227.2009.01336.x}, pmid = {19432824}, issn = {1651-2227}, mesh = {Acute Disease ; Adolescent ; Antibodies, Bacterial/blood/cerebrospinal fluid ; Antibodies, Viral/blood/cerebrospinal fluid ; Candidiasis/diagnosis/microbiology ; Central Nervous System Infections/*diagnosis/microbiology ; Child ; Child, Preschool ; Diagnosis, Differential ; Encephalitis, Viral/diagnosis/virology ; Facial Paralysis/etiology ; Feces/microbiology ; Humans ; Infant ; Lyme Neuroborreliosis/complications/diagnosis/microbiology ; Meningitis, Bacterial/diagnosis/microbiology ; Meningitis, Viral/diagnosis/virology ; Microbiological Techniques/*methods ; Polymerase Chain Reaction ; Prospective Studies ; }, abstract = {AIM: Except bacterial meningitis, the agents causing acute central nervous system (CNS) infections in children are disclosed in only approximately half of the cases, and even less in encephalitis. We studied the potential of modern microbiological assays to improve this poor situation.<br><br>METHODS: In a prospective study during 3 years, all children attending hospital with suspected CNS infection were examined using a wide collection of microbiological tests using samples from the cerebrospinal fluid, serum, nasal swabs and stool.<br><br>RESULTS: Among 213 patients, 66 (31%) cases suggested CNS infection and specific aetiology was identified in 56 patients. Of these microbiologically confirmed cases, viral meningitis/encephalitis was diagnosed in 25 (45%), bacterial meningitis in 21 (38%) and neuroborreliosis in 9 (16%) cases while 1 child had fungal infection. In meningitis patients, the causative agent was identified in 85% (35/41) cases and in encephalitis in 75% (12/16). The most common bacteria were Streptococcus agalactiae, Streptococcous pneumonie and Neisseria meningitidis, while the most frequently detected viruses were enteroviruses and varicella zoster virus.<br><br>CONCLUSION: In 75% to 85% of paediatric CNS infections, specific microbiological diagnosis was obtained with modern laboratory techniques. The results pose a basis for prudent approach to these potentially serious diseases.}, }
@article {pmid19423275, year = {2010}, author = {Vuitton, DA and Bresson-Hadni, S and Giraudoux, P and Bartholomot, B and Laplante, JJ and Delabrousse, E and Blagosklonov, O and Mantion, G}, title = {[Alveolar echinococcosis: from an incurable rural disease to a controlled urban infection].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {39}, number = {2}, pages = {216-230}, doi = {10.1016/j.lpm.2008.10.028}, pmid = {19423275}, issn = {2213-0276}, mesh = {Aftercare ; Albendazole/therapeutic use ; Animals ; Anticestodal Agents/therapeutic use ; China/epidemiology ; Early Diagnosis ; *Echinococcosis, Hepatic/diagnosis/epidemiology/parasitology/therapy ; Echinococcus multilocularis/growth &amp; development ; Endemic Diseases/prevention &amp; control/statistics &amp; numerical data ; Europe/epidemiology ; France/epidemiology ; Humans ; Magnetic Resonance Imaging ; Mass Screening ; Positron-Emission Tomography ; Risk Factors ; Rural Health/*trends ; Tomography, X-Ray Computed ; Urban Health/*trends ; Zoonoses ; }, abstract = {Human alveolar echinococcosis is a parasitic zoonosis with intermediate (rodents and small lagomorphs) and final (carnivores) hosts. The latter can transmit the parasite to humans, by their feces, which are contaminated by the oncospheres of Echinococcus multilocularis, the larvae of which develop in the liver like a slow cancer. Political, socioeconomic, and ecological factors can affect the intermediate and final hosts and thus influence the long-term emergence and stability of endemic areas. The past 20 years have been marked by: Epidemiologic changes: discovery of an endemic area in China, the largest in the world; extension of the European endemic range to the east and north; extension of the French endemic range to the west and south; and the settlement of contaminated foxes in urban centers, which will modify the populations at risk over time. Progress in diagnosis: initial use of liver ultrasound to screen for asymptomatic disease; value of magnetic resonance imaging to confirm diagnosis and assess extension of disease before beginning treatment; mastery of immunological and genetic diagnosis; and the introduction of positron emission tomography combined with computed tomography to assess the functional activity of the lesions and monitor treatment. Consensus has defined the main directions of a multidisciplinary treatment approach: radical liver resection when possible; avoidance of palliative surgical procedures; use of interventional radiology or endoscopy to treat biliary and vascular complications, whenever possible; consideration of liver transplantation only when all other treatment possibilities have been exhausted; and treatment of all patients, without exception, by albendazole for at least two years after radical surgery and long term (at least several years) in other cases. In France, survival and quality of life have improved very substantially, due to earlier diagnosis, clinical classification of cases, and rigorous follow-up as part of the FrancEchino network. Better understanding of the immunological and immunogenetic mechanisms that underlie the course of disease may open up the possibility of immunomodulation that could replace or round out the current treatments. These are far from satisfactory, in view of the constraints of prolonged, most often life-long treatment by benzimidazoles and their side effects.}, }
@article {pmid19404077, year = {2009}, author = {Altomare, DF and Binda, G and Ganio, E and De Nardi, P and Giamundo, P and Pescatori, M and , }, title = {Long-term outcome of Altemeier's procedure for rectal prolapse.}, journal = {Diseases of the colon and rectum}, volume = {52}, number = {4}, pages = {698-703}, doi = {10.1007/DCR.0b013e31819ecffe}, pmid = {19404077}, issn = {1530-0358}, mesh = {Aged ; Blood Loss, Surgical/statistics &amp; numerical data ; Colon, Sigmoid/surgery ; Comorbidity ; Constipation/etiology ; Digestive System Surgical Procedures/*methods ; Fecal Incontinence/etiology ; Female ; Humans ; Length of Stay ; Male ; Manometry ; Rectal Prolapse/complications/epidemiology/*surgery ; Rectum/surgery ; Recurrence ; Reoperation ; Treatment Outcome ; }, abstract = {INTRODUCTION: Altemeier's procedure is infrequently applied in European countries and because of the small number of patients treated in each center, its long-term reliability is uncertain.<br><br>METHODS: Medical records of 93 patients (median age, 77 years) undergoing perineal rectosigmoidectomy associated with levatorplasty in 72 patients (78 percent) were reviewed; 65 patients (70 percent) suffered from major fecal incontinence.<br><br>RESULTS: There was no postoperative mortality. Eight (8.6 percent) major complications were observed (3 pelvic hematomas, 1 anastomotic dehiscence, 1 sigmoid perforation, 1 pararectal abscess, and 2 late anal strictures), and 13 (14 percent) minor complications. At a mean follow-up of 41 (range, 12-112) months the complete recurrence rate was 18 percent (17 patients); these patients were treated with a repeat Altemeier's procedure (6 patients), Delorme's operation (1 patient), Wells' rectopexy (1 patient), postanal repair (1 patient), anal bulking agents (2 patients), and sacral nerve stimulation (2 patients). Anal manometry significantly improved postoperatively. Incontinence improved postoperatively in 30 cases (28 percent), deteriorated in 2 patients, while 4 patients developed minor incontinence.<br><br>CONCLUSIONS: Perineal rectosigmoidectomy for rectal prolapse is a relatively safe and effective treatment, in particular, for frail, older patients, with a low postoperative morbidity, but the recurrence rate is not negligible and restoration of continence is unpredictable.}, }
@article {pmid19394704, year = {2009}, author = {Johnson, S}, title = {Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes.}, journal = {The Journal of infection}, volume = {58}, number = {6}, pages = {403-410}, doi = {10.1016/j.jinf.2009.03.010}, pmid = {19394704}, issn = {1532-2742}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacterial Toxins ; *Clostridioides difficile/pathogenicity ; Cross Infection ; Diarrhea/microbiology ; Enterocolitis, Pseudomembranous/*epidemiology/etiology/*therapy ; Humans ; Metronidazole/therapeutic use ; Recurrence ; Risk Factors ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {Episodes of recurrent Clostridium difficile infection (CDI) are difficult to treat for several reasons. Foremost, data are lacking to support any particular treatment strategy. In addition, treatment of recurrent episodes is not always successful, and repeated, prolonged treatment is often necessary. Identification of subgroups at risk for recurrent CDI may aid in diagnosing and treating these patients. Two likely mechanistic factors increasing the risk of recurrent CDI are an inadequate immune response to C. difficile toxins and persistent disruption of the normal colonic flora. Important epidemiologic risk factors include advanced age, continuation of other antibiotics, and prolonged hospital stays. Current guidelines recommend that the first recurrent episode be treated with the same agent (i.e., metronidazole or vancomycin) used for the index episode. However, if the first recurrence is characterized as severe, vancomycin should be used. A reasonable strategy for managing a subsequent episode involves tapering followed by pulsed doses of vancomycin. Other potentially effective strategies for recurrent CDI include vancomycin with adjunctive treatments, such as Saccharomyces boulardii, rifaximin "chaser" therapy after vancomycin, nitazoxanide, fecal transplantation, and intravenous immunoglobulin. New treatment agents that are active against C. difficile, but spare critical components of the normal flora, may decrease the incidence of recurrent CDI.}, }
@article {pmid19384040, year = {2009}, author = {Prabha, S and Verghese, S}, title = {Detection of porcine rotavirus from tissue and faecal specimens.}, journal = {Indian journal of medical microbiology}, volume = {27}, number = {2}, pages = {149-152}, doi = {10.4103/0255-0857.49430}, pmid = {19384040}, issn = {1998-3646}, mesh = {Animals ; Feces/*virology ; Intestinal Mucosa/*virology ; Molecular Sequence Data ; RNA, Viral/genetics ; Rotavirus/*isolation &amp; purification ; Rotavirus Infections/*veterinary/virology ; Sequence Analysis, DNA ; Swine ; Swine Diseases/*virology ; }, abstract = {Porcine small intestinal sub-mucosa is a cell-free collagen matrix that has demonstrated its ability as a scaffold material. Transplantation poses special hazards because grafted tissues and organs transmit pathogens efficiently, especially viruses. Rotavirus is thought to be confined to the intestine, causing acute diarrhoea. The purpose of this study was to evaluate the porcine intestinal tissue scaffold for Rotavirus and to study the incidence of this virus among pig herds. Only one isolate was successfully adapted to grow in cell line MA 104 from faecal samples. This isolate was further confirmed by reverse transcriptase polymerase chain reaction and sequence analysis.}, }
@article {pmid19333059, year = {2009}, author = {Altomare, DF and Rinaldi, M and Sallustio, PL and Armenise, N}, title = {Giant fecaloma in an adult with severe anal stricture caused by anal imperforation treated by proctocolectomy and ileostomy: report of a case.}, journal = {Diseases of the colon and rectum}, volume = {52}, number = {3}, pages = {534-537}, doi = {10.1007/DCR.0b013e318199db36}, pmid = {19333059}, issn = {1530-0358}, mesh = {Anus Diseases/*etiology ; Anus, Imperforate/*surgery ; Colectomy ; Constriction, Pathologic/*etiology ; Digestive System Surgical Procedures/adverse effects ; Fecal Impaction/etiology/*surgery ; Humans ; Ileostomy ; Male ; Megacolon/etiology/*surgery ; Middle Aged ; Rectum ; Recurrence ; }, abstract = {Although fecalomas are relatively common in patients who are elderly, constipated, or who have spinal injuries, a giant fecaloma formation unresponsive to conservative treatment is a rare condition that sometimes requires surgery for complications. Herein we report a case of a long-lasting (46 years) giant fecaloma associated with severe anal stricture after surgery for anal atresia and resulting in severe malnutrition, bone structural changes, and severe impairment of quality of life. Eight months after treatment by total proctocolectomy and ileostomy, the patient was on a free diet and had gained more than 10 percent of his postoperative body weight; improvements were observed in the tone of the abdominal muscles and in his quality of life.}, }
@article {pmid19325142, year = {2009}, author = {Weibel, GL and Joshi, MR and Alexander, ET and Zhu, P and Blair, IA and Rothblat, GH}, title = {Overexpression of human 15(S)-lipoxygenase-1 in RAW macrophages leads to increased cholesterol mobilization and reverse cholesterol transport.}, journal = {Arteriosclerosis, thrombosis, and vascular biology}, volume = {29}, number = {6}, pages = {837-842}, pmid = {19325142}, issn = {1524-4636}, support = {P30 ES013508-049001/ES/NIEHS NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; R01CA091016/CA/NCI NIH HHS/United States ; P01 HL022633-32A1/HL/NHLBI NIH HHS/United States ; R01 CA091016-08/CA/NCI NIH HHS/United States ; P01 HL022633/HL/NHLBI NIH HHS/United States ; HL-22633/HL/NHLBI NIH HHS/United States ; P30ES013508/ES/NIEHS NIH HHS/United States ; R01 CA091016/CA/NCI NIH HHS/United States ; }, mesh = {ATP Binding Cassette Transporter 1 ; ATP Binding Cassette Transporter, Subfamily G, Member 1 ; ATP-Binding Cassette Transporters/metabolism ; Animals ; Apolipoprotein A-I/metabolism ; Arachidonate 15-Lipoxygenase/genetics/*metabolism ; Biological Transport ; Cell Line ; Cholesterol/*metabolism ; Cholesterol Ester Transfer Proteins/*metabolism ; Cholesterol Esters/metabolism ; Cholesterol, HDL/metabolism ; Feces/chemistry ; Humans ; Hydrolysis ; Hydroxyeicosatetraenoic Acids/metabolism ; Lipoproteins/metabolism ; Lipoproteins, LDL/metabolism ; Macrophages/*enzymology/transplantation ; Mice ; RNA, Messenger/metabolism ; Time Factors ; Transfection ; Tritium ; Up-Regulation ; }, abstract = {OBJECTIVE: The purpose of this study was to determine the effect of 15-lipoxygenase-1 (15-LO-1) on cholesterol mobilization from macrophages.<br><br>METHODS AND RESULTS: Overexpression of human 15-LO-1 in RAW mouse macrophages led to enhanced cholesterol efflux, increased cholesteryl ester (CE) hydrolysis, and increased reverse cholesterol transport (RCT). Efflux studies comparing 15-LO-1 overexpressing cells to mock-transfected RAW macrophages resulted in a 3- to 7-fold increase in cholesterol efflux to apolipoprotein A-I and a modest increase in efflux to HDL. Additional experiments revealed an increase in mRNA and protein levels of ABCA1 and ABCG1 in the RAW expressing 15-LO-1 compared to controls. Efforts to examine whether the arachidonic acid metabolite of 15-LO-1, (15S)-hydroxyeicosatetraenoic acid (HETE), was responsible for the enhanced efflux revealed this eicosanoid metabolite did not play a role. Enhanced steryl ester hydrolysis was observed in 15-LO-1 overexpressing cells suggesting that the CE produced in the 15-LO-1 expressing cells was readily mobilized. To measure RCT, RAW macrophages overexpressing 15-LO-1 or mock-transfected cells were cholesterol enriched by exposure to acetylated low-density lipoprotein and [(3)H]-cholesterol. These macrophages were injected into wild-type animals and RCT was measured as a percent of injected dose of (3)H appearing in the feces at 48 hours. We found 7% of the injected (3)H in the feces of mice that received macrophages overexpressing 15-LO-1 and 4% in the feces of mice that received mock-transfected cells.<br><br>CONCLUSIONS: These data are consistent with a model in which overexpression of human 15-LO-1 in RAW macrophages promotes RCT through increased CE hydrolysis and ABCA1-mediated cholesterol efflux.}, }
@article {pmid19288244, year = {2009}, author = {Galvão, FH and Seid, VE and Nunes dos Santos, RM and Kitamura, M and de Castro Galvão, R and Ambar Pinto, R and Miyashiro Nunes dos Santos, R}, title = {Anorectal transplantation.}, journal = {Techniques in coloproctology}, volume = {13}, number = {1}, pages = {55-59}, pmid = {19288244}, issn = {1128-045X}, mesh = {Anal Canal/*transplantation ; Animals ; Colostomy/*methods ; Defecation ; Disease Models, Animal ; Fecal Incontinence/physiopathology/*surgery ; Male ; Rats ; Rats, Wistar ; Rectum/*transplantation ; Treatment Outcome ; }, abstract = {BACKGROUND: Anorectal transplantation is a valid procedure for the treatment of anorectal dysfunction; however, the lack of a suitable animal model has hampered the development of this method. We describe a simple technique for anorectal transplantation in the rat and compare this procedure with colostomy.<br><br>METHODS: The anorectal segment including the skin surrounding the anus were freed by abdominal and perineal dissection. In a heterotopically transplanted group the segment was exteriorized by the formation of an anus through an abdominal incision. In an orthotopically transplanted group the segment was replaced in its original position and reimplanted by suturing. In another group a distal colostomy was performed. A sham-treated control group (simulated surgical procedure) was also included. Changes in behavior, characteristics of the stool, body weight and survival rate were assessed by daily clinical examination. Moribund animals, those with a weight loss of more than 30%, and those surviving at 1 month were killed by an overdose of anesthetic. The results were analyzed using the Mann Whitney, Student's t and chi-squared tests, and p<0.05 was considered significant.<br><br>RESULTS: Within 4 days after the operation, animals submitted to orthotopic or heterotopic transplantation had achieved normal defecation, body weight gain and clinical evolution similar to the sham-treated group. The overall mortality in these groups was 4.16%. In contrast, colostomized animals showed a high incidence of diarrhea, intestinal obstruction, stress posture and violent behavior (p</=0.05), and a mortality rate of 58.33%.<br><br>CONCLUSION: Autotransplantation in the rat is a simple technique, achieves a high rate of success and better clinical evolution than colostomy. This model may ultimately lead to research into anorectal transplantation.}, }
@article {pmid19279426, year = {2009}, author = {Aigner, F and Conrad, F and Margreiter, R and Oberwalder, M and , }, title = {Anal submucosal carbon bead injection for treatment of idiopathic fecal incontinence: a preliminary report.}, journal = {Diseases of the colon and rectum}, volume = {52}, number = {2}, pages = {293-298}, doi = {10.1007/DCR.0b013e318197d755}, pmid = {19279426}, issn = {1530-0358}, mesh = {Aged ; Anal Canal/physiopathology ; Carbon/*administration &amp; dosage ; Coated Materials, Biocompatible/*administration &amp; dosage ; Fecal Incontinence/physiopathology/*therapy ; Female ; Glucans/*administration &amp; dosage ; Humans ; Injections ; Manometry ; Microspheres ; Middle Aged ; Quality of Life ; Zirconium/*administration &amp; dosage ; }, abstract = {PURPOSE: Submucosal injection of bulking agents is a treatment option for idiopathic fecal incontinence. This study sought to assess whether the injection of carbon beads can significantly improve anal continence.<br><br>METHODS: Consecutive patients presenting with fecal incontinence were evaluated with standardized incontinence grading and quality-of-life grading scores, by anoproctoscopy, endoanal ultrasound, and anomanometry before, 3, 6, 12, and 24 months after injection. Injection therapy was performed in patients with anatomically intact anal sphincters. Patients kept a two-week incontinence diary. Data were obtained from a two-year follow-up period.<br><br>RESULTS: Eleven women with a mean age of 66 (range, 56 to 74) years met the inclusion criteria. Mean incontinence score was 12.27 +/- 0.97 at baseline, 6.82+/-1.64 at three-month, 6.73 +/- 1.47 at six-month, 5.91 +/- 0.95 at one-year, and 4.91 +/- 0.87 at two-year follow-up (P = 0.003). Quality-of-life items like coping and embarrassment improved significantly from baseline 2.3 to 3 at three months and 2.8 at six months (P < 0.05). Anomanometry showed a trend toward increase in measured pressures. No major complications occurred.<br><br>CONCLUSIONS: The injection of carbon beads via an intersphincteric approach is a promising new treatment option for old patients with idiopathic fecal incontinence.}, }
@article {pmid19273965, year = {2009}, author = {Ardelean, MA and Bauer, J and Schimke, C and Ludwikowski, B and Schimpl, G}, title = {Improvement of continence with reoperation in selected patients after surgery for anorectal malformation.}, journal = {Diseases of the colon and rectum}, volume = {52}, number = {1}, pages = {112-118}, doi = {10.1007/DCR.0b013e3181972333}, pmid = {19273965}, issn = {1530-0358}, mesh = {Anal Canal/*abnormalities/surgery ; Child ; Child, Preschool ; Fecal Incontinence/etiology/physiopathology/*surgery ; Female ; Humans ; Male ; Postoperative Complications ; Rectum/*abnormalities/surgery ; Reoperation ; Urinary Tract/abnormalities/surgery ; }, abstract = {PURPOSE: Fecal incontinence is a serious complication after repair of anorectal malformations. We investigated whether reoperation can improve fecal continence.<br><br>METHODS: Medical records of 41 patients (40 children and one adult; 26 male and 15 female) who underwent reoperation after previous reconstruction of an anorectal malformation were reviewed for outcomes of bowel function. Type of primary corrective surgery performed, therapeutic measures, results of physical examination and barium enema, and reoperation procedures were evaluated. A questionnaire was administered to assess stool behaviour and level of continence at follow-up three or more years after secondary operation.<br><br>RESULTS: Secondary operations in males comprised posterior sagittal anorectoplasty (PSARP) in 16 patients, PSARP with antegrade continent enema in one patient, antegrade continent enema alone in 6, anoplasty in one, rectosigmoid resection in 1, and definitive colostomy in 1 patient. Secondary operations in females included PSARP alone in 4 patients, PSARP with total urogenital mobilization in 4, PSARP with vaginoplasty in 2, PSARP with vaginoplasty and antegrade continent enema in 2, and PSARP with vaginourethroplasty in 3. Of 41 patients 18 (44 percent) were continent at follow-up, 21 (51 percent) were clean with use of enemas, diet, or drug therapy. One patient had a definitive colostomy. One died after kidney transplantation.<br><br>CONCLUSIONS: Surgery is a good option for improving incontinence in selected patients previously operated for anorectal malformations. Posterior sagittal anorectoplasty is advocated to improve bowel control. Antegrade continent enema is a reliable therapeutic option to maintain clean patients with fecal incontinence.}, }
@article {pmid19273950, year = {2009}, author = {Altomare, DF and Ratto, C and Ganio, E and Lolli, P and Masin, A and Villani, RD}, title = {Long-term outcome of sacral nerve stimulation for fecal incontinence.}, journal = {Diseases of the colon and rectum}, volume = {52}, number = {1}, pages = {11-17}, doi = {10.1007/DCR.0b013e3181974444}, pmid = {19273950}, issn = {1530-0358}, mesh = {*Electric Stimulation Therapy/adverse effects ; Electrodes, Implanted/adverse effects ; Fecal Incontinence/etiology/*therapy ; Female ; Humans ; *Lumbosacral Plexus ; Male ; Middle Aged ; Quality of Life ; }, abstract = {PURPOSE: Sacral nerve stimulation is a safe and effective procedure for fecal incontinence. We investigated whether its efficacy is maintained long term.<br><br>PATIENTS AND METHODS: Sixty patients with fecal incontinence underwent permanent sacral nerve stimulation. Patients' data were prospectively recorded in the national registry of the Italian Group of sacral nerve stimulation. The severity of fecal incontinence was evaluated by the Wexner score, and data were collected in a bowel function diary. Quality of life was evaluated by the Italian version of the Medical Outcomes Survey Short Form (SF-36) questionnaire.<br><br>RESULTS: Fifty-two patients were available for long-term follow-up lasting at least 5 years. Compared with baseline, the Wexner score decreased significantly after definitive implantation (from 15 +/- 4 to 5 +/- 5, P < 0.001). At least 50 percent improvement in continence was achieved in 74 percent of the patients, and at least 70 percent improvement (median value) was achieved in 50 percent. The mean number of solid/liquid incontinence episodes decreased significantly from 0.5 (+/-0.5) to 0.1 (+/-0.3) per day (P = 0.004). Quality of life improved in all domains. The overall mean improvement in SF-36 scores was 39.8 percent. Both mean resting and squeeze anal pressures increased significantly, and maximum volume tolerated decreased significantly.<br><br>CONCLUSIONS: Sacral nerve stimulation maintains its efficacy long term, not only in regard to control of symptoms but also regarding quality of life.}, }
@article {pmid19237460, year = {2009}, author = {Kalippke, K and Werwitzke, S and von Hornung, M and Mischke, R and Ganser, A and Tiede, A}, title = {DNA analysis from stool samples: a fast and reliable method avoiding invasive sampling methods in mouse models of bleeding disorders.}, journal = {Laboratory animals}, volume = {43}, number = {4}, pages = {390-393}, doi = {10.1258/la.2008.008057}, pmid = {19237460}, issn = {0023-6772}, mesh = {Animals ; DNA/genetics/*isolation &amp; purification ; Disease Models, Animal ; Factor VIII/genetics ; Feces/*chemistry ; Female ; Genotype ; Hemophilia A/*diagnosis/genetics ; Male ; Mice ; Mice, Knockout ; Polymerase Chain Reaction/*methods ; Receptors, IgG/genetics ; }, abstract = {Mouse models with targeted disruptions of coagulation factor genes are used to study disorders of haemostasis such as haemophilia. Standard protocols to obtain biopsies for genotyping in breeding programmes are based on invasive sampling methods such as tail clipping. These procedures imply a high risk of fatal bleeding, especially in haemophilic mouse models. Here we used a non-invasive sampling method obtaining stool samples for DNA isolation in a breeding programme, aiming to introduce targeted disruptions of Fc receptor genes (Fc gamma receptor IIB and III) into the haemophilia A mouse model (factor VIII deficiency). Faecal pellets were reliably obtained from individual mice and high-quality DNA was extracted with a mean yield of 7.1 microg/pellet. Polymerase chain reaction amplification of wild-type and knockout alleles for Fc receptor and factor VIII genes was similar, comparing stool and peripheral blood as the source of genomic DNA. Definite genotype identification was achieved in a first attempt in 336 of 352 analyses (95%). Repeated analysis of homozygous knockout animals confirmed the first result in all cases. No animal was lost due to bleeding from the procedure. In conclusion, DNA isolation from stool is a preferable method for genotyping in laboratory animals, especially in models of bleeding disorders. Avoiding loss of animals due to bleeding implies a substantial improvement in animal welfare by reducing the number of animals used and may also advance the effectiveness of breeding programmes in these disease models.}, }
@article {pmid19207221, year = {2010}, author = {Siahi-Benlarbi, R and Nies, SM and Sziegoleit, A and Bauer, J and Schranz, D and Wetzel, WE}, title = {Caries-, Candida- and Candida antigen/antibody frequency in children after heart transplantation and children with congenital heart disease.}, journal = {Pediatric transplantation}, volume = {14}, number = {6}, pages = {715-721}, doi = {10.1111/j.1399-3046.2008.01115.x}, pmid = {19207221}, issn = {1399-3046}, mesh = {Adolescent ; Antibodies, Bacterial/*analysis ; Antigens, Bacterial/*analysis ; Candida/*isolation &amp; purification ; Candidiasis/prevention &amp; control ; Candidiasis, Oral/epidemiology ; Child ; Child, Preschool ; Dental Caries/*microbiology ; Dental Plaque/microbiology ; Feces/*microbiology ; Female ; Health Status ; Heart Defects, Congenital/*microbiology ; Heart Transplantation/*immunology ; Humans ; Immunocompromised Host ; Male ; Mannans/immunology ; Saliva/microbiology ; }, abstract = {The aim of this study was to determine the incidence of oral/intestinal Candida colonization and Candida-antigen/antibody in immunosuppressed children after HTx (group III, n = 31), in children with CHD (group II, n = 24) and in children with healthy hearts (comparison group, group I, n = 23) aged 2-16 yr according to their dental status between 2004 and 2007. Candida species in saliva, dental plaque, carious lesions and stool were detected with Sabouraud-/CHROMagar and Auxacolor system. Candida-specific-antigen/antibody assays were used for serological diagnosis. Dental status was determined on the basis of the DMF/dmf(T/t)-index. We found significant group differences in fecal Candida colonization (p = 0.027). In relation to dental status, oral Candida colonization increased within group III from 28.5% [DMF/dmf(T/t) = 0] to 66.7% [DMF/dmf(T/t) > or = 1] up to 100.0% [D/d(T/t) > or = 1], similar in groups I and II. Candida-mannan-antigen was determined to be positive in 16.1% (HTx), 5.5% (CHD) and 13.0% (comparison group). We show correlation between oral Candida colonization and (carious) dental status. We assume that high oral Candida and their descending/resorption through the gastrointestinal tract may lead to serologic Candida accumulation or rather candidiasis. Therefore, healthy oral cavity (especially before/after HTx) is an important precondition to prevent Candida infections.}, }
@article {pmid19188339, year = {2009}, author = {Wong, G and Webster, AC and Chapman, JR and Craig, JC}, title = {Reported cancer screening practices of nephrologists: results from a national survey.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {24}, number = {7}, pages = {2136-2143}, doi = {10.1093/ndt/gfp009}, pmid = {19188339}, issn = {1460-2385}, mesh = {Adult ; Aged ; Chronic Disease ; Female ; Humans ; Kidney Diseases/complications ; Male ; Mass Screening ; Middle Aged ; Neoplasms/complications/*diagnosis ; *Nephrology ; *Practice Patterns, Physicians' ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Cancer is becoming increasingly recognized as a complication of chronic kidney disease (CKD), and screening is a widely used strategy to reduce cancer risk and improve outcomes. This study aimed to describe cancer screening practices by nephrologists in Australia and New Zealand, and to identify reasons for a positive recommendation to screen.<br><br>METHODS: Questionnaires were posted electronically to all nephrologists who were in adult clinical practice in 2007 using the Australia-New Zealand Society of Nephrology register. The survey instrument assessed nephrologists' reported practice towards colorectal, breast and cervical cancer screening across all stages of CKD (CKD 1-5, dialysis and transplantation).<br><br>RESULTS: Of the 250 eligible members, 131 (52%) participated, with over 75% recommending breast cancer screening (usually 1-2 yearly using combined mammography and breast-self examination), 48% recommending colorectal cancer screening (1-2 yearly faecal occult blood test) and 86% recommending cervical cancer screening (1-2 yearly conventional cytology). Recommendations to screen did not vary appreciably with CKD status. Recommended screening strategies were more frequent, included more invasive tests, and were targeted at a broader age range than national cancer screening programmes in the general population. Increased cancer prevalence and cancer-specific mortality benefits for screening were the most commonly reported and influential criteria for making a positive recommendation.<br><br>CONCLUSIONS: Most nephrologists recommend breast and cervical, but not colorectal cancer screening in people with CKD. Despite the lack of trial-based evidence of benefits of screening in this setting, recommended screening practices by nephrologists are more intense than for the general population. Increased disease prevalence appears to be the most influential factor for making a positive recommendation to screen in the CKD population even though this is not an internationally accepted criterion for a screening programme, and is not relevant for breast cancer, which is not increased in the CKD population.}, }
@article {pmid19137878, year = {2008}, author = {Ma, Y and Bi, H and Xia, Y and Yang, X and Li, J}, title = {[Vaginal reconstruction with modified pudendal-thigh flap].}, journal = {Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery}, volume = {22}, number = {12}, pages = {1415-1417}, pmid = {19137878}, issn = {1002-1892}, mesh = {Adult ; Circumcision, Female/*methods ; Female ; Humans ; Male ; Skin Transplantation ; Surgical Flaps ; Transsexualism/*surgery ; Vagina/*surgery ; }, abstract = {OBJECTIVE: To increase the success rate of vaginal reconstruction with pudendal-thigh flap, reduce the chance of hemocirculatory disorder and relieve the deformity of greater lip of pudendum and vaginal orifice.<br><br>METHODS: From June 1998 to May 2004, 15 patients, 2 males with transsexualism and 13 females with vaginal absence, aged 23-31 years old (26.2 on average), received vaginal reconstruction. Arterial perforator was detected at 3 cm laterally away from the mid-point between the vaginal orifice and the anus. The flap of 12.0 cm x 5.5 cm was designed at the lateral of the greater lip of pudendum, with the groin as the axis. After the flap was elevated beneath the deep fascia, the fascial pedicle was partially severed from lateral to medium, keeping the perforator intact into the flap. Then the flap was transferred through the tunnel to the socket. The inner layer and the orifice were formed.<br><br>RESULTS: All flaps survived, and the contour of the vulva was satisfactory. Among the 15 patients, 14 patients' incisions obtained healing by first intention, and only 1 male with transsexualism was discovered to suffer from rectovaginal fistula at the remote juncture of the two flaps at 7 days after the operation. By taking out all the gauze and cleaning the feces, the fistula healed automatically. All patients were followed up for 6 months-3 years. The reconstructed vagina was about 10 cm deep and 2 fingers wide. One female's vagina was found pilous at 20 months after the operation, and no special treatment was given. The other patients' vaginal inner walls were smooth and complete. Two female patients had the experience of sexual intercourse and felt satisfied after using lubricant.<br><br>CONCLUSION: The modified pudendal-thigh flap has reliable blood supply and makes the transferring during vaginal reconstruction more convenient and the contour of the vulva more satisfactory.}, }
@article {pmid19116886, year = {2009}, author = {Huang, KY and Chia, JH and Chiang, CY and Wu, TL and Su, LH and Jaing, TH and Lin, TY and Chiu, CH}, title = {Prolonged fecal shedding of CTX-M-15-producing Escherichia coli and recurrent sepsis in a patient after cord blood stem-cell transplantation.}, journal = {Scandinavian journal of infectious diseases}, volume = {41}, number = {3}, pages = {224-227}, doi = {10.1080/00365540802680391}, pmid = {19116886}, issn = {0036-5548}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Cord Blood Stem Cell Transplantation/*adverse effects ; Escherichia coli/drug effects/genetics/*isolation &amp; purification/metabolism ; Escherichia coli Infections/complications/drug therapy/*microbiology ; Feces/*microbiology ; Female ; Graft vs Host Disease/complications/drug therapy ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/therapeutic use ; Infant ; Polymerase Chain Reaction ; Recurrence ; Sepsis/complications/drug therapy/*microbiology ; beta-Lactam Resistance/genetics ; beta-Lactamases/*genetics ; }, abstract = {An extended-spectrum beta-lactamase (CTX-M-15 type)-producing Escherichia coli persisted in the intestinal tract for >5 months in a pediatric patient after cord blood stem-cell transplantation and caused 2 episodes of sepsis. The bla(CTX-M-15) is carried by a large plasmid of approximately 130 kb in size. The prolonged shedding of the highly resistant E. coli posed a great challenge to infection control and public health.}, }
@article {pmid19100548, year = {2009}, author = {Samyn, H and Moerland, M and van Gent, T and van Haperen, R and Grosveld, F and van Tol, A and de Crom, R}, title = {Elevation of systemic PLTP, but not macrophage-PLTP, impairs macrophage reverse cholesterol transport in transgenic mice.}, journal = {Atherosclerosis}, volume = {204}, number = {2}, pages = {429-434}, doi = {10.1016/j.atherosclerosis.2008.10.020}, pmid = {19100548}, issn = {1879-1484}, mesh = {Animals ; Apolipoprotein A-I/genetics/metabolism ; Atherosclerosis/blood/*enzymology ; Biological Transport ; Cells, Cultured ; Cholesterol/*metabolism ; Feces/chemistry ; High-Density Lipoproteins, Pre-beta/metabolism ; Humans ; Liver/metabolism ; Macrophages, Peritoneal/*enzymology/transplantation ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Phospholipid Transfer Proteins/blood/genetics/*metabolism ; }, abstract = {Phospholipid transfer protein (PLTP) is a multifunctional protein synthesized by various cell types and secreted into the plasma. Plasma PLTP is able to transfer phospholipids between lipoproteins and modulate HDL particles. Mice with overexpression of human PLTP have an increased ability to generate pre beta-HDL, reduced total HDL levels and an increased susceptibility to atherosclerosis. As the macrophage is a key component of the atherosclerotic lesion and an important site of PLTP expression, we investigated the role of systemic and peripheral PLTP in macrophage cholesterol efflux and reverse cholesterol transport (RCT) in vivo. We used an assay in which (3)H-labelled cholesterol-loaded macrophages were injected intraperitoneally into recipient mice, and radioactivity was quantified in plasma, liver and faeces. Firstly, wild type macrophages were injected into wild type, PLTP transgenic (PLTPtg) and apoAI transgenic (apoAItg) mice. While plasma (3)H-tracer levels in apoAItg mice were increased compared with wild type mice, they were reduced in PLTPtg mice. Moreover, overexpression of PLTP significantly decreased faecal (3)H-tracer levels compared with wild type and apoAItg mice. Secondly, wild type mice were injected with peritoneal macrophages derived from PLTPtg or wild type mice. No significant difference in the amount of (3)H-tracer in plasma, liver or faeces was found between the two groups of mice. Our findings demonstrate that macrophage cholesterol efflux and RCT to faeces is impaired in PLTP transgenic mice, and that elevation of macrophage-PLTP does not affect RCT, indicating that higher systemic PLTP levels may promote atherosclerosis development by decreasing the rate of macrophage RCT.}, }
@article {pmid19100483, year = {2008}, author = {Wu, SW and Chang, HR and Tsao, SM and Wu, YL and Yao, CC and Lian, JD}, title = {A Salmonella infection complicated with suppurative thyroiditis and ruptured aortic mycotic aneurysm in a renal transplant recipient.}, journal = {Transplantation proceedings}, volume = {40}, number = {10}, pages = {3759-3763}, doi = {10.1016/j.transproceed.2008.06.057}, pmid = {19100483}, issn = {0041-1345}, mesh = {Aged ; Anti-Bacterial Agents/therapeutic use ; Aorta, Thoracic/surgery ; Aortic Aneurysm, Thoracic/drug therapy/*microbiology/surgery ; Aortic Rupture/drug therapy/*microbiology/surgery ; Blood/microbiology ; C-Reactive Protein/metabolism ; Creatinine/blood ; Drug Therapy, Combination ; Feces/microbiology ; Humans ; Hypertension/etiology ; Immunosuppressive Agents/therapeutic use ; Kidney Failure, Chronic/surgery ; *Kidney Transplantation ; Male ; Salmonella Infections/*diagnosis/drug therapy ; *Salmonella enteritidis/isolation &amp; purification ; Treatment Outcome ; }, abstract = {We report a renal transplant recipient who presented with fever and chills for 2 days. The blood and stool cultures revealed the growth of Salmonella enteriditis. A whole-body gallium scan played an important role in the subsequent diagnosis of suppurative thyroiditis. To our knowledge, this is the first report of acute S. enteriditis thyroiditis in a renal transplant recipient. Despite vigorous antibiotic use and a partial thyroidectomy, he experienced recurrent S. enteriditis infection, resulting in a ruptured thoracic mycotic aneurysm 1 month later. Finally the patient was successfully cured with aneurysm resection, in situ reconstruction of the thoracic aorta, and prolonged antibiotics.}, }
@article {pmid19094674, year = {2008}, author = {Yu, MH and Yu, XL and Chen, CL and Gao, LH and Mao, WL and Yan, D and Chen, Y and Sheng, JF and Li, LJ and Zheng, SS}, title = {[The change of intestinal microecology in rats after orthotopic liver transplantation].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {46}, number = {15}, pages = {1139-1142}, pmid = {19094674}, issn = {0529-5815}, mesh = {Animals ; Bacterial Translocation ; Endotoxins/blood ; Intestines/*microbiology/ultrastructure ; *Liver Transplantation ; Male ; Random Allocation ; Rats ; }, abstract = {OBJECTIVE: To investigate the intestinal microflora status and bacterial translocation in rats after liver transplantation.<br><br>METHODS: Male Brown-Norway (BN) rats were randomly divided into 4 groups: group I (n = 8) for liver transplantation; group II (n = 8) for simulated liver transplantation; group III (n = 8) for sham operation and group IV (n = 8) for normal group. Caecal bacterial counts, plasma endotoxin, intestinal mucosal ultrastructure and bacterial translocation to liver, spleen, kidney, and mesenteric lymph node were studied 24 h after surgery.<br><br>RESULTS: The numbers of Bifidobacterium and Lactobacillus per gram of wet feces were significantly decreased in group I compare with those in the group III and group IV, while Enterobacteriaceae and Enterococcus counts were increased markedly compare with those in the group III and group IV, but no different was found between group I and group II. Impaired intestinal mucosa integrity were found in the group I and group II. In group I, the levels of plasma endotoxin increased after the transplantation when compare with group III and group IV. Increased incidence of bacterial translocation to liver, spleen and mesenteric lymph node were also observed after the transplantation (compare with those in the group IV, P < 0.01; compare with those in the group III, P < 0.01, P < 0.01, P < 0.05, separately). The increased rate of the bacterial translocation in liver was also found in transplantation group as compare with group II (P < 0.05).<br><br>CONCLUSIONS: Liver transplantation may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function, and this dysfunction might be caused by the process of intestinal ischemia-reperfusion injury in transplantation.}, }
@article {pmid19090774, year = {2009}, author = {Alexander, JP and Ehresmann, K and Seward, J and Wax, G and Harriman, K and Fuller, S and Cebelinski, EA and Chen, Q and Jorba, J and Kew, OM and Pallansch, MA and Oberste, MS and Schleiss, M and Davis, JP and Warshawsky, B and Squires, S and Hull, HF and , }, title = {Transmission of imported vaccine-derived poliovirus in an undervaccinated community in Minnesota.}, journal = {The Journal of infectious diseases}, volume = {199}, number = {3}, pages = {391-397}, doi = {10.1086/596052}, pmid = {19090774}, issn = {0022-1899}, mesh = {Adolescent ; Amino Acid Sequence ; Antigens, Viral/chemistry/genetics ; Bone Marrow Transplantation ; Child, Preschool ; Feces/virology ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Infant ; Minnesota ; Phylogeny ; Poliomyelitis/prevention &amp; control/*transmission/virology ; Poliovirus/*classification/genetics/*isolation &amp; purification ; Poliovirus Vaccines/*administration &amp; dosage/immunology ; Severe Combined Immunodeficiency/*complications/therapy ; Time Factors ; }, abstract = {BACKGROUND: Oral poliovirus vaccine (OPV) has not been used in the United States since 2000. Type 1 vaccine-derived poliovirus (VDPV) was identified in September 2005, from an unvaccinated Amish infant hospitalized in Minnesota with severe combined immunodeficiency. An investigation was conducted to determine the source of the virus and its means of transmission.<br><br>METHODS: The infant was tested serially for poliovirus excretion. Investigations were conducted to detect poliovirus infections or paralytic poliomyelitis in Amish communities in Minnesota, neighboring states, and Ontario, Canada. Genomic sequences of poliovirus isolates were determined for phylogenetic analysis.<br><br>RESULTS: No source for the VDPV could be identified. In the index community, 8 (35%) of 23 children tested, including the infant, had evidence of type 1 poliovirus or VDPV infection. Phylogenetic analysis suggested that the VDPV circulated in the community for approximately 2 months before the infant's infection was detected and that the initiating OPV dose had been given before her birth. No paralytic disease was found in the community, and no poliovirus infections were found in other Amish communities investigated.<br><br>CONCLUSIONS: This is the first demonstrated transmission of VDPV in an undervaccinated community in a developed country. Continued vigilance is needed in all countries to identify poliovirus infections in communities at high risk of poliovirus transmission.}, }
@article {pmid19034367, year = {2008}, author = {Bedoya, K and Montoya, MN and Botero, J and Galván, AL}, title = {[First isolate of Encephalitozoon intestinalis from stools of a Colombian patient with AIDS].}, journal = {Biomedica : revista del Instituto Nacional de Salud}, volume = {28}, number = {3}, pages = {441-447}, pmid = {19034367}, issn = {0120-4157}, mesh = {Acquired Immunodeficiency Syndrome/*parasitology ; Animals ; Cattle ; Cell Line ; Colombia ; Encephalitozoon/*isolation &amp; purification ; Feces/*parasitology ; Humans ; Microsporidia/*isolation &amp; purification ; Middle Aged ; }, abstract = {INTRODUCTION: Microsporidia are obligate intracellular parasites that are recognized as important opportunistic pathogens of immunocompromised and transplanted patients. Enterocytozoon bieneusi and, less frequently, Encephalitozoon intestinalis are the most prevalent species in humans; both of them are associated with enteric infections. Cell cultures have been useful in the study of microsporidia biology. In Colombia, however, no isolates of microsporidia from patients with AIDS have been obtained.<br><br>OBJECTIVE: A cell culture of intestinal microsporidia was established from stools of positive patients in order to isolate a native strain.<br><br>MATERIALS AND METHODS: Stool from a single AIDS patient was concentrated with the water-ether technique, and the sediment was treated with a mixture of antibiotics and antifungal agents for 18 hours at 37 degrees C. Vero cells were cultivated in 24-well plates with Gibco RPMI medium supplemented with 10% bovine fetal serum and antibiotics. The culture was subsequently inoculated with previously concentrated spores. The medium was changed every second day and the presence of spores was evaluated with the Quick Hot Gram chromotrope stain.<br><br>RESULTS: Two weeks post-infection, microsporidial spores were identified with characteristic morphology and staining properties. PCR results showed that Encephalitozoon intestinalis was the isolated species.<br><br>CONCLUSIONS: A cell culture of microsporidia was established from a stool sample. This protocol is important to isolate and maintain additional native Colombian strains and it will contribute to biochemical, immunological and epidemiological studies of the currently established strain.}, }
@article {pmid18926216, year = {2008}, author = {Sauvat, F and Grimaldi, C and Lacaille, F and Ruemmele, F and Dupic, L and Bourdaud, N and Fusaro, F and Colomb, V and Jan, D and Cezard, JP and Aigrain, Y and Revillon, Y and Goulet, O}, title = {Intestinal transplantation for total intestinal aganglionosis: a series of 12 consecutive children.}, journal = {Journal of pediatric surgery}, volume = {43}, number = {10}, pages = {1833-1838}, doi = {10.1016/j.jpedsurg.2008.03.028}, pmid = {18926216}, issn = {1531-5037}, mesh = {Adult ; Child ; Child, Preschool ; Diarrhea/drug therapy/epidemiology/etiology ; Enterostomy ; Feeding Methods ; Female ; Gastric Bypass ; Graft Rejection/drug therapy/epidemiology/prevention &amp; control ; Hirschsprung Disease/complications/*surgery ; Humans ; Infant ; Intestines/*transplantation ; Jaundice, Obstructive/etiology/surgery ; Liver Cirrhosis/etiology/surgery ; *Liver Transplantation ; Male ; Postoperative Care ; Postoperative Complications/epidemiology/etiology ; Reoperation ; Sepsis/epidemiology/etiology ; Survival Rate ; Tissue Donors/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Management of patients with total intestinal aganglionosis (TIA) is a medical challenge because of their dependency on parenteral nutrition (PN). Intestinal transplantation (ITx) represents the only alternative treatment for patients with irreversible intestinal failure for achieving intestinal autonomy.<br><br>METHODS: Among 66 patients who underwent ITx in our center, 12 had TIA. They received either isolated ITx (n = 4) or liver-ITx (LITx, n = 8) after 10 to 144 months of total PN. All grafts included the right colon.<br><br>RESULTS: After a median follow-up of 57 months, the survival rate was 62.5% in the LITx group and 100% in the ITx patients. The graft survival rate was 62.5% in the LITx group and 75% in the ITx group. All the surviving patients were fully weaned from total PN, after a median of 57 days. Pull through of the colon allograft was carried out in all patients. Fecal continence is normal in all but one of the surviving children.<br><br>CONCLUSION: These results suggest that ITx with colon grafting should be the preferred therapeutic option in TIA. Early referral to a transplantation center after diagnosis of TIA is critical to prevent PN-related cirrhosis and thereby to permit ITx, which is associated with a good survival rate.}, }
@article {pmid18836489, year = {2009}, author = {Wong, AS and Cheng, VC and Yuen, KY and Kwong, YL and Leung, AY}, title = {High frequency of polyoma BK virus shedding in the gastrointestinal tract after hematopoietic stem cell transplantation: a prospective and quantitative analysis.}, journal = {Bone marrow transplantation}, volume = {43}, number = {1}, pages = {43-47}, pmid = {18836489}, issn = {1476-5365}, mesh = {BK Virus/genetics/isolation &amp; purification/*physiology ; Feces/virology ; Gastrointestinal Tract/chemistry/*virology ; Graft vs Host Disease/immunology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Polymerase Chain Reaction ; Polyomavirus Infections/immunology/urine/*virology ; Prospective Studies ; Tumor Virus Infections/immunology/urine/*virology ; Virus Latency ; Virus Shedding ; }, abstract = {The polyoma BK virus (BKV) remains latent after primary infection and may reactivate during immunosuppression. The uroepithelium is the main latency site defined. This study addressed whether the gastrointestinal tract might be another latency site. To test this hypothesis, we prospectively quantified fecal BKV by quantitative PCR reaction in 40 patients undergoing hematopoietic SCT (HSCT). Urinary BKV was similarly quantified. Fecal BKV excretion was positive in 16/40 patients, of whom 10 were transient (<3 consecutively positive samples), six were persistent (> or =3 consecutively positive samples) and three were persistent with peaking (> or =10(3)-fold increase in viral load over baseline, reaching 5.11 x 10(6), 4.68 x 10(7) and 2.75 x 10(8) copies/sample at 14, 14 and 21 days post-HSCT, respectively). Urinary BKV excretion was positive in 25/40 patients. Fecal BKV excretion was significantly correlated with that of the urine (P=0.036) and was significantly associated with allogeneic HSCT (P=0.037) and persistent and peaking of urinary BKV excretion (P<0.001). Binary logistic regression showed that BKV viruria was the only significant risk factor for fecal BKV excretion (P=0.021). Fecal BKV excretion occurred in 40% patients undergoing HSCT, implicating the gastrointestinal tract as a BKV latency site.}, }
@article {pmid18814482, year = {2008}, author = {Nomoto, K}, title = {Prevention of postoperative microbial infection by synbiotics.}, journal = {Indian journal of experimental biology}, volume = {46}, number = {8}, pages = {557-561}, pmid = {18814482}, issn = {0019-5189}, mesh = {Animals ; Feces/microbiology ; Humans ; Infections/complications/*diet therapy/*microbiology ; Postoperative Complications/diet therapy/*microbiology/*prevention &amp; control ; Probiotics/*pharmacology/*therapeutic use ; }, abstract = {Prevention of infectious complications after major surgeries including those for cancer has been a major concern in the clinical field. To overcome this problem, probiotics and synbiotics (combination of probiotics and prebiotics have recently been introduced for post-operative treatment. Clinical application of synbiotics in severe cases, such as severe pediatric surgical cases, acute pancreatitis, liver transplantation, and biliary cancer, has been reported. The present article deals with the clinical effect of such synbiotic therapies for the patients under emergency medical care, and discusses the possible mechanism of action and prospect of synbiotic therapy.}, }
@article {pmid18781540, year = {2009}, author = {Nomura, K and Fujimoto, Y and Yamashita, M and Morimoto, Y and Ohshiro, M and Sato, K and Oyake, T and Kowata, S and Konishi, H and Yoshikawa, T and Ishida, Y and Taniwaki, M and , }, title = {Absence of pseudomembranes in Clostridium difficile-associated diarrhea in patients using immunosuppression agents.}, journal = {Scandinavian journal of gastroenterology}, volume = {44}, number = {1}, pages = {74-78}, doi = {10.1080/00365520802321238}, pmid = {18781540}, issn = {1502-7708}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/therapeutic use ; Anti-Infective Agents/therapeutic use ; Bacterial Toxins/analysis ; *Clostridioides difficile/isolation &amp; purification ; Colitis, Ulcerative/drug therapy/microbiology/*pathology ; Colonoscopy ; Diarrhea/*microbiology ; Drug Therapy, Combination ; Enterocolitis, Pseudomembranous/drug therapy/microbiology/*pathology ; Enterotoxins/analysis ; Feces/chemistry/microbiology ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/*administration &amp; dosage ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {OBJECTIVE: Clostridium difficile is a major cause of diarrhea in hospitalized patients. Although pseudomembranes are crucial evidence for diagnosis of C. difficile-associated diarrhea (CDAD), some cases do not show any pseudomembranes. The aim of this study was to verify the hypothesis that pseudomembranes are not generated in immunosuppressed patients because of the absence of immunoreactions.<br><br>MATERIAL AND METHODS: We investigated the endoscopic findings of patients with ulcerative colitis (UC) or who had received hematopoietic stem cell transplantation, and who presented with C. difficile toxin A and had undergone colonoscopy between April 2002 and July 2007 at our institutes. Results. In 4 patients the diagnosis was UC and C. difficile infection, and in another 4 patients the diagnosis was CDAD after hematopoietic stem cell transplantation. None of these cases showed pseudomembranes. Shallow ulcers were found in all four cases with UC. Only non-specific findings were obtained for the CDAD patients after hematopoietic stem cell transplantation.<br><br>CONCLUSIONS: Pseudomembranes, the typical evidence for CDAD, were not detected in any patients using immunosuppressive agents. Additional bacterial examination is therefore essential when UC becomes exacerbated and when patients present with diarrhea after hematopoietic stem cell transplantation, even in the absence of pseudomembranes.}, }
@article {pmid18756332, year = {2008}, author = {Shelat, VG and Diddapur, RK}, title = {Duodenal carcinoid: a rare cause of melaena in a cirrhotic patient.}, journal = {Singapore medical journal}, volume = {49}, number = {8}, pages = {e198-201}, pmid = {18756332}, issn = {2737-5935}, mesh = {Adult ; Carcinoid Tumor/*complications/diagnosis ; Duodenal Neoplasms/*complications/diagnosis ; Duodenum/pathology ; Endoscopy/methods ; Humans ; Liver Cirrhosis/*diagnosis/*therapy ; Male ; Melena/*diagnosis/*etiology ; Neoplasm Metastasis ; Neuroendocrine Tumors/*complications/diagnosis ; Prognosis ; Tomography, X-Ray Computed/methods ; Treatment Outcome ; }, abstract = {Small intestinal neuroendocrine tumours are relatively rare. Laboratory tests and diagnostic imaging are of help in diagnosis. Surgical resection is the standard approach. Metastatic disease has a poor prognosis. These are indolent tumours and hence role of chemotherapy is limited. Radionuclide and biological therapies are emerging. We report a 29-year-old man presenting with melaena and diagnosed as having a neuroendocrine tumour of the duodenum together with liver cirrhosis. Standard Whipple's procedure was done and he is doing well at follow-up.}, }
@article {pmid18719190, year = {2008}, author = {Savini, V and Di Bartolomeo, E and Catavitello, C and Talia, M and Manna, A and Febbo, F and Balbinot, A and Di Bonaventura, G and Di Bartolomeo, P and Piccolomini, R and D'Antonio, D}, title = {Graft versus host disease-related Hafnia alvei colonization and probable infection.}, journal = {Journal of medical microbiology}, volume = {57}, number = {Pt 9}, pages = {1167-1169}, doi = {10.1099/jmm.0.2008/001164-0}, pmid = {18719190}, issn = {0022-2615}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Carrier State/drug therapy/*microbiology ; Child ; Enterobacteriaceae Infections/complications/drug therapy/*microbiology ; Fanconi Anemia/complications/therapy ; Feces/microbiology ; Female ; Gastroenteritis/complications/drug therapy/*microbiology ; Graft vs Host Disease/*complications ; Hafnia alvei/drug effects/*isolation &amp; purification ; Humans ; Immunocompromised Host ; Stem Cell Transplantation ; }, abstract = {We describe the case of a graft versus host disease (GvHD) patient, in whom Hafnia alvei was cultured as a single organism, and at high bacterial counts from stool samples, from the onset of the disease until its resolution. This case is a further example of the contentious role of this species in causing human intestinal disease. Furthermore, it focuses on enteric damage by GvHD as a risk factor for acquiring H. alvei colonization, and probably infection.}, }
@article {pmid18698248, year = {2008}, author = {Sabbagh, F and El Tawil, Z and Lecerf, F and Hulin, A and Maurois, P and Dartevelle, P and Bac, P and German-Fattal, M}, title = {Impact of cyclosporine A on magnesium homeostasis: clinical observation in lung transplant recipients and experimental study in mice.}, journal = {Transplantation}, volume = {86}, number = {3}, pages = {436-444}, doi = {10.1097/TP.0b013e31817fe069}, pmid = {18698248}, issn = {0041-1337}, mesh = {Administration, Oral ; Adolescent ; Adult ; Animals ; Creatinine/blood ; Cyclosporine/*adverse effects ; *Dietary Supplements ; Disease Models, Animal ; Female ; Homeostasis ; Humans ; Immunosuppressive Agents/*adverse effects ; Kidney Diseases/blood/*chemically induced ; *Lung Transplantation ; Magnesium/*blood ; Magnesium Deficiency/blood/*chemically induced/prevention &amp; control ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Pyrrolidonecarboxylic Acid/administration &amp; dosage/*therapeutic use ; Retrospective Studies ; Time Factors ; Treatment Failure ; }, abstract = {BACKGROUND: Hypomagnesemia is a common finding in patients receiving cyclosporine A (CsA) therapy. The relationship between CsA-induced hypomagnesemia and nephrotoxicity and the effects of oral magnesium (Mg) supplementation remain unclear. After a retrospective analysis of the time-course of plasma Mg and creatinine levels in lung allograft recipients treated with both CsA and oral Mg supplementation, we investigated the effects of CsA treatment on Mg homeostasis in mice with normal or Mg-deficient diet and the effects of oral Mg supplementation on plasma Mg levels.<br><br>METHODS: Thirty lung-allograft recipients entered the retrospective study. One thousand two hundred twenty-eight blood samples were analyzed for blood and creatinine levels. Cyclosporine A (50 mg/kg/day by intraperitoneal injection) was administered to mice maintained on normal diet (1400 ppm) or Mg-deficient (50 ppm) diet. Magnesium levels were determined in plasma, urine, feces and femur, and creatinine levels were determined in plasma and urine.<br><br>RESULTS: Plasma Mg concentration declines from the day of transplantation in 36.7% of the patients despite Mg supplementation, without correlation with creatinine changes. In mice, CsA induced an early moderate hypomagnesemia, which could not be ameliorated by oral Mg supplementation and was aggravated by low-Mg dietary, late increase in plasma creatinine and decrease in urine creatinine without histological signs of renal injury, decrease in intestinal Mg absorption and Mg mobilization from bone.<br><br>CONCLUSION: Cyclosporine A treatment may induce moderate hypomagnesemia that is aggravated by inadequate Mg intake and is not ameliorated by Mg supplementation. Because of the clinical complications of hypomagnesemia, Mg should be monitored regularly in allograft recipients receiving CsA.}, }
@article {pmid18684006, year = {2009}, author = {Eisengart, LJ and Chou, PM and Iyer, K and Cohran, V and Rajaram, V}, title = {Rotavirus infection in small bowel transplant: a histologic comparison with acute cellular rejection.}, journal = {Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society}, volume = {12}, number = {2}, pages = {85-88}, doi = {10.2350/08-05-0473.1}, pmid = {18684006}, issn = {1093-5266}, mesh = {Adolescent ; Biopsy ; Child ; Child, Preschool ; Diagnosis, Differential ; Diarrhea/diagnosis/etiology ; Endoscopy, Gastrointestinal ; Enteritis/*diagnosis/virology ; Feces/virology ; Female ; Graft Rejection/*diagnosis/immunology ; Humans ; Infant ; Intestine, Small/*transplantation/*virology ; Male ; Postoperative Complications ; Rotavirus/*isolation &amp; purification ; Rotavirus Infections/*pathology ; }, abstract = {Pediatric small bowel transplant recipients are susceptible to diarrhea due to rejection or infectious enteritis, particularly of viral etiology. The most common causes of viral enteritis in this setting are rotavirus, adenovirus, cytomegalovirus, and Epstein-Barr virus. This study is the first to compare the histologic findings of rotavirus infection with acute cellular rejection in small bowel transplant biopsies. Three patients with small bowel transplants had rapid stool antigen test-proven rotavirus infection. Endoscopic biopsies during infection were examined, including material from the allograft, native small bowel, stomach, and colon. Biopsies from 2 of the patients during unrelated episodes of mild acute cellular rejection were also evaluated. Blunting of villi was the most common finding in rotavirus infection. Additionally, there was a mononuclear infiltrate that was "top heavy," or denser towards the lumen. There were surface apoptoses but no increase in crypt apoptotic figures. In contrast, during mild acute cellular rejection, there was no villous blunting, the mononuclear infiltrate was diffuse, and there were increased crypt apoptosis. As expected, the changes of acute cellular rejection were confined to the graft, in contrast to rotavirus infection, in which case native bowel often had more pronounced changes. Although the small number of patients limits this study, several histologic features were helpful in identifying rotavirus infection. These were blunting of villi, distribution of the inflammatory infiltrate, number and location of apoptotic bodies, and anatomic location of the effect. A larger follow-up study would be valuable to confirm these findings.}, }
@article {pmid18585877, year = {2009}, author = {Leon-Quinto, T and Simon, MA and Cadenas, R and Jones, J and Martinez-Hernandez, FJ and Moreno, JM and Vargas, A and Martinez, F and Soria, B}, title = {Developing biological resource banks as a supporting tool for wildlife reproduction and conservation The Iberian lynx bank as a model for other endangered species.}, journal = {Animal reproduction science}, volume = {112}, number = {3-4}, pages = {347-361}, doi = {10.1016/j.anireprosci.2008.05.070}, pmid = {18585877}, issn = {1873-2232}, mesh = {Animals ; *Animals, Wild/physiology ; *Biological Specimen Banks/supply &amp; distribution ; Conservation of Natural Resources/*methods ; *Extinction, Biological ; Female ; Germ Cells/cytology/physiology ; Lynx/*physiology ; Male ; Nuclear Transfer Techniques/veterinary ; Reproduction/physiology ; *Reproductive Techniques, Assisted ; Tissue and Organ Harvesting/methods/veterinary ; }, abstract = {This work presents a Biological Resource Bank generated as a complementary supporting tool for the reproduction and the in situ and ex situ conservation of the Iberian lynx. In its design we prioritized the preservation of a maximum of the current genetic and biological diversity of the population, and the harmless collection of the samples. To provide future reproductive opportunities through any possible technique, we processed and cryopreserved germinal cells and tissues from dead animals, 7 males and 6 females, as well as somatic cells and tissues from 69 different individuals. This somatic cell reserve reflects a very important fraction of the population biodiversity which, furthermore, will allow the development of a wide variety of studies that can be easily extrapolated to the majority of the population. We have developed a new non-destructive method to isolate cells with stem-cell-like properties. If considered convenient in the future, and after proper research, such cells could permit therapeutic applications and perhaps be a good source to be used in somatic cell nuclear transfer. Samples of whole blood and its derivatives, hairs, urine and feces from many different individuals were also preserved. Proper storage of such samples is required to allow epidemiological studies to be performed for the testing of different etiological hypotheses or, in general, to develop any bio-sanitary study to improve conservation strategies within the natural habitat. This work describes the main aspects involved in the practical implementation of the Iberian lynx Biological Resource Bank, as a model that could be useful for the development of similar banks for other endangered species.}, }
@article {pmid18555639, year = {2008}, author = {Faucheron, JL}, title = {[Anal incontinence].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {37}, number = {10}, pages = {1447-1462}, doi = {10.1016/j.lpm.2008.04.004}, pmid = {18555639}, issn = {2213-0276}, mesh = {Anal Canal/embryology/injuries/innervation/surgery ; Artificial Organs ; Electric Stimulation Therapy/methods ; Fecal Incontinence/classification/epidemiology/etiology/*therapy ; France/epidemiology ; Humans ; Muscle, Skeletal/transplantation ; Prevalence ; Rupture/complications ; Severity of Illness Index ; }, abstract = {Anal incontinence today is more frequent than current estimates indicate. When a patient seeks care for this condition, its cause and severity are assessed by a careful history and clinical examination. Two essential atraumatic examinations are decision-support tools: transrectal ultrasound and anal manometry. Treatment should always be proposed. Surgery is necessary in some cases: obvious rupture of the external sphincter, if possible confirmed by transrectal ultrasound, should be directly repaired. Should this treatment fail, a repeated repair or a sphincter replacement (graciloplasty or artificial sphincter) is called for. Neuromodulation therapy is often indicated in the absence of obvious rupture, especially in cases of pudendal neuropathy.}, }
@article {pmid18536965, year = {2008}, author = {Kang, SB and Lee, HN and Lee, JY and Park, JS and Lee, HS and Lee, JY}, title = {Sphincter contractility after muscle-derived stem cells autograft into the cryoinjured anal sphincters of rats.}, journal = {Diseases of the colon and rectum}, volume = {51}, number = {9}, pages = {1367-1373}, pmid = {18536965}, issn = {1530-0358}, mesh = {Acetylcholine/pharmacology ; Anal Canal/*injuries/pathology/*physiopathology ; Animals ; Cells, Cultured ; Cholinergic Agents/pharmacology ; Cold Temperature/adverse effects ; Fecal Incontinence/etiology/*therapy ; Female ; Models, Animal ; Muscle Contraction/*physiology ; Muscle, Skeletal/*cytology ; Rats ; Rats, Sprague-Dawley ; *Stem Cell Transplantation ; Transplantation, Autologous ; }, abstract = {PURPOSE: This study was designed to determine whether the injection of muscle-derived stem cells into the anal sphincter can improve functional properties in a fecal incontinence rat model.<br><br>METHODS: Cryoinjured rats were utilized as a fecal incontinence model. The gastrocnemius muscles of normal three-week-old female Sprague-Dawley rats were used for the purification of the muscle-derived stem cells. The experimental group was divided into three subgroups: normal control; cryoinjured; and muscle-derived stem cells (3 x 10(6) cells) injection group of cryoinjured rats. All groups were subsequently employed in contractility experiments using muscle strips from the anal sphincter, one week after preparation.<br><br>RESULTS: Contractility in the cryoinjured group was significantly lower than in the control after treatment with acetylcholine and KCl. In the muscle-derived stem cells injection group, contraction amplitude was higher than in the cryoinjured group but not significantly (20.5 +/- 21.3 vs. 17.3 +/- 3.4 g per gram tissue, with acetylcholine (10(-4) mol/l); 31 +/- 14.2 vs. 18.4 +/- 7.9 g per gram tissue, with KCl (10(-4) mol/l)). PKH-26-labeled transplanted cells were detected in all of the grafted sphincters. Differentiated muscle masses stained positively for alpha smooth muscle actin and myosin heavy chain at the muscle-derived stem cells injection sites.<br><br>CONCLUSIONS: This is the first study reporting that autologous muscle-derived stem cell grafts may be a tool for improving anal sphincter function.}, }
@article {pmid18509413, year = {2008}, author = {Mandavilli, A}, title = {Microbiology: straight from the gut.}, journal = {Nature}, volume = {453}, number = {7195}, pages = {581-582}, doi = {10.1038/453581a}, pmid = {18509413}, issn = {1476-4687}, mesh = {Adult ; Defensins/metabolism ; *Ecosystem ; Feces/*microbiology ; Female ; Humans ; Infant, Newborn ; Intestines/*microbiology/*transplantation ; Models, Biological ; Nod2 Signaling Adaptor Protein/genetics/metabolism ; }, }
@article {pmid18506922, year = {2008}, author = {Sgourakis, G and Sotiropoulos, GC and Molmenti, EP and Eibl, C and Bonticous, S and Moege, J and Berchtold, C}, title = {Are acute exacerbations of chronic inflammatory appendicitis triggered by coprostasis and/or coproliths?.}, journal = {World journal of gastroenterology}, volume = {14}, number = {20}, pages = {3179-3182}, pmid = {18506922}, issn = {1007-9327}, mesh = {Acute Disease ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Appendectomy ; Appendicitis/classification/*etiology/pathology/surgery ; Appendix/pathology/surgery ; Child ; Child, Preschool ; Chronic Disease ; Fecal Impaction/*complications ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Risk Factors ; Terminology as Topic ; }, abstract = {AIM: To examine the role of coprostasis and coproliths in recurrent appendicitis.<br><br>METHODS: We evaluated four hundred and twenty seven consecutive pathology reports of all appendectomy specimens from January 2003 to December 2004. Findings were categorised as showing acute appendicitis, acute recurrent appendicitis, subacute recurrent appendicitis, chronic appendicitis, or appendices without inflammation. All patients had presented with acute right lower quadrant pain. In 94 instances, there was a history of recurrent similar episodes in the past.<br><br>RESULTS: Of the 427 histology reports, 294 were inter-preted as showing acute appendicitis, 56 acute recurrent appendicitis, 34 subacute recurrent appen-dicitis, 28 chronic appendicitis, and 15 non-inflamed appendices. Coprostasis was observed in 58 patients (13.58%) and the presence of coprolith in 6 (1.4%). Coprostasis, and age, were among the predictors in the final model.<br><br>CONCLUSION: Coprostasis but not coproliths seems to be a contributing factor to acute exacerbations of chronic inflammatory appendicitis.}, }
@article {pmid18475184, year = {2008}, author = {Akpinar, E and Vargas, J and Kato, T and Smith, L and Hernandez, E and Selvaggi, G and Nishida, S and Moon, J and Island, E and Levi, D and Ruiz, P and Tzakis, AG}, title = {Fecal calprotectin level measurements in small bowel allograft monitoring: a pilot study.}, journal = {Transplantation}, volume = {85}, number = {9}, pages = {1281-1286}, doi = {10.1097/TP.0b013e31816dcea2}, pmid = {18475184}, issn = {0041-1337}, mesh = {Feces/*chemistry ; Follow-Up Studies ; Graft Survival ; Humans ; Ileostomy ; Intestine, Small/*transplantation ; Leukocyte L1 Antigen Complex/*analysis ; Monitoring, Physiologic/methods ; Pilot Projects ; Retrospective Studies ; Transplantation, Homologous/mortality/physiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Protocol endoscopy with biopsy is currently the gold standard of small bowel transplantation (SBTx) monitoring, however it is invasive, costly, needs skilled operator, may require anesthesia and may cause complications. We investigated fecal calprotectin level (FCL) as a candidate noninvasive marker for monitoring patients after SBTx.<br><br>METHODS: A pilot study was performed to test the use of FCL measurement in following up SBTx patients. Ileostomy effluents were collected at various postoperative days before endoscopy and biopsy. FCLs were measured by enzyme-linked immunosorbent assay and a cut-off level of 100 ng/mg was considered positive. The results were retrospectively evaluated in combination with clinical, endoscopic, and histopathological findings. FCLs are presented as median nanogram per milligram.<br><br>RESULTS: FCLs were measured in 122 samples that were obtained from 29 patients after SBTx. Only 1 of 69 positive FCL did not accompany abnormal findings. Retrospective evaluation showed that 11 samples from six patients (FCL: 217) coincided with rejection episodes, six samples from three patients (FCL: 125) coincided with viral enteritis, 51 samples from 21 patients (FCL: 207) coincided with nonspecific inflammation, 11 samples from two patients (FCL: 998) coincided with chronic intestinal ulceration, and finally 50 samples from 19 patients (FCL: 43) coincided with normal findings. No significant FCL difference was found between rejection, infection, and inflammation. FCL evolution in individuals showed that FCL can predict rejection days before histopathological diagnosis.<br><br>CONCLUSION: FCL is a sensitive test for ongoing organic intestinal allograft pathologies. It might be useful as prescreening marker to avoid unnecessary endoscopies.}, }
@article {pmid18473503, year = {2008}, author = {Catalán González, M and Montejo González, JC}, title = {[Anidulafungin: a new therapeutic approach in antifungal therapy. Pharmacology of anidulafungin].}, journal = {Revista iberoamericana de micologia}, volume = {25}, number = {2}, pages = {92-100}, doi = {10.1016/s1130-1406(08)70026-3}, pmid = {18473503}, issn = {1130-1406}, mesh = {Anidulafungin ; Antifungal Agents/*pharmacology/*therapeutic use ; Echinocandins/*pharmacology/*therapeutic use ; Humans ; Mycoses/*drug therapy ; }, abstract = {Anidulafungin is a new echinocandin antifungal agent which inhibits beta-1,3-D-glucan synthase and disrupts fungal cell-wall synthesis. It has marked antifungal activity against Candida spp. and Aspergillus spp., including amphotericin B and triazole resistant strains. Due to the limited oral availability, anidulafungin in clinical use is available for parenteral administration only. Elimination of anidulafungin takes place via slow non-enzymatic degradation to inactive metabolites. Less than 10% and 1% of the initially administered drug is excreted unchanged into feces and urine, respectively. It does not require dosage adjustment in subjects with hepatic or renal impairment established. Anidulafungin is generally well tolerated. Adverse events appear not to be dose or infusion related. The most common treatment related adverse events are phlebitis, headache, nausea, vomiting and pyrexia. The lack of interactions with tacrolimus, cyclosporine and corticosteroids and its limited toxicity profile places anidulafungin as an attractive new option for the treatment of invasive fungal infections especially in transplant patients.}, }
@article {pmid18449613, year = {2008}, author = {Cho, CS and Dayton, MT and Thompson, JS and Koltun, WA and Heise, CP and Harms, BA}, title = {Proctocolectomy-ileal pouch-anal anastomosis for ulcerative colitis after liver transplantation for primary sclerosing cholangitis: a multi-institutional analysis.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {12}, number = {7}, pages = {1221-1226}, pmid = {18449613}, issn = {1873-4626}, mesh = {Adult ; Aged ; Anal Canal/*surgery ; Anastomosis, Surgical/methods ; Cholangitis, Sclerosing/*surgery ; Colitis, Ulcerative/etiology/*surgery ; *Colonic Pouches ; Female ; Humans ; Liver Transplantation/*adverse effects ; Male ; Middle Aged ; Proctocolectomy, Restorative/*methods ; Treatment Outcome ; }, abstract = {BACKGROUND: The association between primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) often mandates their contemporaneous management. Orthotopic liver transplantation (OLTX) has emerged as the only curative therapy for PSC, and total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the definitive treatment for refractory UC. The published experience to date describing IPAA after OLTX has been limited; we sought to examine outcomes associated with proctocolectomy-IPAA after OLTX.<br><br>MATERIALS AND METHODS: We reviewed our multi-institutional experience performing proctocolectomy-IPAA for UC after OLTX for PSC.<br><br>RESULTS: Twenty-two patients underwent proctocolectomy-IPAA for UC after OLTX for PSC at four academic medical centers between 1989 and 2006. No perioperative complications or allograft dysfunction were observed. During a median follow-up of 52 months, complications have included transient dehydration (n = 6), chronic pouchitis (n = 2), recurrent PSC (n = 2), small bowel obstruction (n = 2), and pouch-anal anastomotic stricture (n = 1). Median 24-h stool frequency was 5, and fecal continence was reported as satisfactory by all patients.<br><br>CONCLUSIONS: This multi-institutional experience suggests that proctocolectomy-IPAA can be performed safely after OLTX. Management strategies should include optimization of small bowel length during pouch and ileostomy construction, vigorous postoperative hydration, early ileostomy closure, and careful monitoring for pouchitis.}, }
@article {pmid18420997, year = {2008}, author = {Sehayek, E and Hazen, SL}, title = {Cholesterol absorption from the intestine is a major determinant of reverse cholesterol transport from peripheral tissue macrophages.}, journal = {Arteriosclerosis, thrombosis, and vascular biology}, volume = {28}, number = {7}, pages = {1296-1297}, pmid = {18420997}, issn = {1524-4636}, support = {P01 HL087018/HL/NHLBI NIH HHS/United States ; P01 HL076491/HL/NHLBI NIH HHS/United States ; P01HL077107/HL/NHLBI NIH HHS/United States ; P01 HL076491-04/HL/NHLBI NIH HHS/United States ; P50 HL077107-040004/HL/NHLBI NIH HHS/United States ; P50 HL077107/HL/NHLBI NIH HHS/United States ; P01HL087018/HL/NHLBI NIH HHS/United States ; P01HL076491/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Anticholesteremic Agents/*pharmacology ; Azetidines/*pharmacology ; Cell Line ; Cell Transplantation ; Cholesterol, Dietary/blood/*metabolism ; Ezetimibe ; Feces/chemistry ; Female ; Intestinal Absorption/*drug effects/genetics ; Intestines/*drug effects ; Kinetics ; Lipid Metabolism/drug effects/genetics ; Macrophages/*drug effects/metabolism/transplantation ; Mice ; Mice, Congenic ; Mice, Inbred C57BL ; Sitosterols/metabolism ; }, abstract = {OBJECTIVE: We examined the effect of ezetimibe, a cholesterol absorption (CA) inhibitor, and genetic determinants of CA on reverse cholesterol transport (RCT) from subcutaneously injected macrophages using a new dual isotope label technique.<br><br>METHODS AND RESULTS: Treatment of C57BL/6J mice with ezetimibe decreased dietary CA by 86% and increased RCT from peripheral tissue macrophages (PTM) by 6-fold (P<0.0001). Moreover, congenic 14DKK mice with a modest 41% decrease in dietary CA displayed a 67% increase in RCT from PTM (P<0.007).<br><br>CONCLUSIONS: These findings indicate that pharmacological and genetic modifiers of cholesterol absorption are major determinants of reverse cholesterol transport from peripheral tissue macrophages.}, }
@article {pmid18394823, year = {2009}, author = {Abbassi, MS and Achour, W and Touati, A and Ben Hassen, A}, title = {Enterococcus faecium isolated from bone marrow transplant patients in Tunisia: high prevalence of antimicrobial resistance and low pathogenic power.}, journal = {Pathologie-biologie}, volume = {57}, number = {3}, pages = {268-271}, doi = {10.1016/j.patbio.2008.02.008}, pmid = {18394823}, issn = {1768-3114}, mesh = {Ampicillin Resistance ; Anti-Bacterial Agents/pharmacology ; Bacterial Infections/*drug therapy/epidemiology ; Bone Marrow Transplantation/*adverse effects ; Drug Resistance, Microbial ; Drug Resistance, Multiple ; Enterococcus faecium/drug effects/*isolation &amp; purification ; Feces/microbiology ; Glycopeptides/pharmacology ; Gram-Positive Bacterial Infections/*epidemiology/*transmission ; Humans ; Postoperative Complications/microbiology ; Tunisia/epidemiology ; }, abstract = {OBJECTIVES: Investigation of the occurrence and antibiotic susceptibility of Enterococcus faecium isolates, collected during four years from neutropenic patients at the Tunisian bone marrow transplantation centre.<br><br>MATERIALS AND METHODS: E. faecium strains were identified by conventional methods and by the Api20 Strep (Bio-M&#xe9;rieux, France). Antibiotic susceptibility was determined by the disk diffusion method on Mueller-Hinton agar and interpreted as recommended by CA-SFM. MICs of ampicillin, vancomycin, and teicoplanin were determined by E-test method.<br><br>RESULTS: Two hundred and thirty five E. faecium isolates were recovered from stool cultures or rectal swabs (229), throat (three), urine (two), and pus of wound (one). None was responsible for bacteraemia. Ampicillin resistance, without production of beta-lactamase, was observed in 43.8% of isolates. All the isolates were susceptible to glycopeptides. High rates of resistance were observed: high-level resistance (HLR) to gentamicin (33.6%), HLR to kanamycin (55.7%), HLR to streptomycin (47.6%), erythromycin (86.4%), ciprofloxacin (78.7%), rifampicin (85%), and tetracycline (43%). Strains with HLR to gentamicin were significantly more resistant to ampicillin and streptomycin. Multiple drug resistance was observed in most isolates.<br><br>CONCLUSION: These findings demonstrated the low pathogenic power of E. faecium in our patients, and the high frequencies of resistance to ampicillin and aminoglycosides. In the absence of glycopeptide-resistance, vancomycin remains an alternative treatment against multidrug resistant strains.}, }
@article {pmid18382384, year = {2008}, author = {Mattner, F and Sykora, KW and Meissner, B and Heim, A}, title = {An adenovirus type F41 outbreak in a pediatric bone marrow transplant unit: analysis of clinical impact and preventive strategies.}, journal = {The Pediatric infectious disease journal}, volume = {27}, number = {5}, pages = {419-424}, doi = {10.1097/INF.0b013e3181658c46}, pmid = {18382384}, issn = {0891-3668}, mesh = {Adenoviridae/classification/genetics/*isolation &amp; purification ; Adenoviridae Infections/*epidemiology/physiopathology/prevention &amp; control/*virology ; Adolescent ; Antiviral Agents/therapeutic use ; Blood/virology ; Bone Marrow Transplantation/adverse effects ; Capsid Proteins/genetics ; Child ; Child, Preschool ; Cidofovir ; Cross Infection/*epidemiology/physiopathology/prevention &amp; control/*virology ; Cytosine/analogs &amp; derivatives/therapeutic use ; DNA, Viral/chemistry/genetics ; *Disease Outbreaks ; Feces/virology ; Gastroenteritis/virology ; Genotype ; Germany/epidemiology ; Hepatitis, Viral, Human/virology ; Humans ; Infant ; Organophosphonates/therapeutic use ; Sequence Analysis, DNA ; Viral Load ; Viremia ; Virus Shedding ; }, abstract = {BACKGROUND: Adenovirus (HAdV) was identified in blood and stool specimens from 6 children on a pediatric bone marrow transplant (BMT) unit within 2 weeks. Two further adenovirus positive patients were identified in other areas of the childrens' hospital. The study aimed to determine the clinical course of different HAdV subtypes and to investigate whether the cluster was caused by nosocomial transmission or by endogenous reactivation.<br><br>METHODS: Descriptive epidemiologic investigation was performed reviewing patients' charts. Molecular typing of identified adenovirus-DNA was performed by partial sequencing of the hexon gene.<br><br>RESULTS: In 6 of 8 patients, HAdV-F41 was detected in feces. All but 1 patient presented with vomiting or diarrhea and all were treated with cidofovir. In 4 patients transmissions of HAdV-F41 within the hematological department were probable whereas 2 children on the BMT ward reactivated HAdV-C1 and -C2, respectively. HAdV-F41 was shed in feces for up to 64 days after onset of clinical symptoms. HAdV-F41 DNA in blood reached a maximum of 2 x 10(5) copies/mL. One patient harbored two HAdV types simultaneously, HAdV-F41 in feces and HAdV-C2 in blood samples. HAdV-C2 reached high virus concentrations in blood (4 x 10(9) copies/mL) and led to the only fatal case. Although the HAdV-F41 outbreak involving 6 children led to gastroenteritis and may also have been associated with mild hepatitis, coincidental, endogeneous reactivations of other HAdV types (C1 and C2) led to a more severe course.<br><br>CONCLUSIONS: HAdV typing is essential both for the prognosis and for distinguishing between transmission or endogenous reactivation. Applying HAdV-specific infection control measures is crucial to prevent transmission.}, }
@article {pmid18362402, year = {2008}, author = {Ağirbasli, H and Bilgen, H and Ozcan, SK and Otlu, B and Sinik, G and Cerikçioğlu, N and Durmaz, R and Can, E and Yalman, N and Gedikoğlu, G and Sugita, T}, title = {Two possible cases of Trichosporon infections in bone-marrow-transplanted children: the first case of T. japonicum isolated from clinical specimens.}, journal = {Japanese journal of infectious diseases}, volume = {61}, number = {2}, pages = {130-132}, pmid = {18362402}, issn = {1344-6304}, mesh = {Antibiotics, Antineoplastic/therapeutic use ; Antifungal Agents/therapeutic use ; Bone Marrow Transplantation/*immunology ; Child ; Fatal Outcome ; Female ; Humans ; Idarubicin/therapeutic use ; Immunocompromised Host ; Infant ; Itraconazole/therapeutic use ; Leukemia, Myeloid, Acute/*therapy ; Male ; Mycoses/*complications/drug therapy ; Neutropenia/complications ; Opportunistic Infections/complications/*microbiology ; Polymerase Chain Reaction ; Trichosporon/classification/genetics/*isolation &amp; purification ; }, abstract = {Trichosporon spp. are emerging as opportunistic agents that cause systemic diseases in immunocompromised hosts. Trichosporonosis carries a poor prognosis in neutropenic patients. Trichosporon japonicum was isolated from the air and named by Sugita et al. Here we present the first case of T. japonicum isolated from a clinical specimen. Two cases of acute myeloid leukemia who had Trichosporon isolates are discussed because of their rarity and growing importance. T. asahii was isolated from the throat, feces and urine of the first patient. T. japonicum was isolated from the sputum of the second patient. Both cases produced high MICs to itraconazole, and low MICs to fluconazole and voriconazole. In virulance factor investigations there was (++) biofilm formation in T. japonicum but not in T. asahii. Conventional mycological studies were not adequate for the identification of the isolate at the species level. In our second case as in the first one, the isolate was identified as T. asahii with 99.9% accuracy by API 20C AUX. Although two T. asahii isolates from the same patient yielded identical typing profiles by arbitrary primed-PCR, the isolates of the two different patients showed different arbitrary primed-PCR typing profiles. However, the genetic identification of the other patient's strain gave the result of T. japonicum.}, }
@article {pmid18309007, year = {2008}, author = {Wong, G and Chapman, JR and Craig, JC}, title = {Cancer screening in renal transplant recipients: what is the evidence?.}, journal = {Clinical journal of the American Society of Nephrology : CJASN}, volume = {3 Suppl 2}, number = {Suppl 2}, pages = {S87-S100}, pmid = {18309007}, issn = {1555-905X}, mesh = {Cost-Benefit Analysis ; Evidence-Based Medicine ; Humans ; *Kidney Transplantation ; Mass Screening/economics ; Neoplasms/*diagnosis/economics/*epidemiology ; Postoperative Complications/*diagnosis/*epidemiology ; Risk Factors ; }, abstract = {Increased cancer risk is well established in the renal transplant population. Little, however, is known about the benefits and harms of cancer screening, treatment effectiveness, and the overall cancer prognosis in renal transplant recipients. In this study, we critically appraised guidelines for cancer screening in the renal transplant and general populations using standard criteria for an evidence-based screening program. Guidelines were included when they were applied to adult participants, had objectives specific to cancer screening, and were written in English. Recommendations for breast and colorectal cancer screening in the general population were supported by evidence of cancer-specific mortality benefits from randomized, controlled trials of cancer screening. Convincing evidence from observational studies had demonstrated population cervical cancer screening was effective, also, test performance of mammography, faecal occult blood testing, and Pap smear were accurate. Population breast, colorectal, and cervical cancer screening also appeared to be good value for money in the general population. On the contrary, recommendations for cancer screening in renal transplant recipients were entirely extrapolated from data in the general population. Studies in the general population have led to the development of cancer screening guidelines in transplant recipients. Because of increased cancer risk, differences in diagnostic test performance, competing risks for deaths from causes such as cardiovascular disease and reduced overall life expectancies, validity of their recommendations are uncertain. Future studies are needed to address these issues to provide the necessary evidence for informed decision-making.}, }
@article {pmid18347531, year = {2008}, author = {Wong, G and Howard, K and Craig, JC and Chapman, JR}, title = {Cost-effectiveness of colorectal cancer screening in renal transplant recipients.}, journal = {Transplantation}, volume = {85}, number = {4}, pages = {532-541}, doi = {10.1097/TP.0b013e3181639d35}, pmid = {18347531}, issn = {0041-1337}, mesh = {Colorectal Neoplasms/economics/*epidemiology ; Cost-Benefit Analysis ; Humans ; *Kidney Transplantation/mortality/physiology ; Markov Chains ; Reproducibility of Results ; Sensitivity and Specificity ; Survival Analysis ; Survivors ; }, abstract = {BACKGROUND: Colorectal cancer screening is now standard practice in most developed countries. The aim of this study was to determine the cost-effectiveness of colorectal cancer screening, with annual fecal occult blood testing, in renal transplant recipients.<br><br>METHOD: A Markov model was developed to compare the effects of annual fecal occult blood testing (FOBT) as screening for colorectal cancer in a cohort of renal transplant recipients ages 50-70 years, versus no screening. Data on cancer risk and survival were obtained from the ANZDATA Registry. Accuracy of FOBT, cancer stage distribution of the screened and unscreened arms, and adverse effects of colonoscopy were extrapolated from general population data because of unavailability of equivalent data in renal transplant recipients.<br><br>RESULTS: When the participation rate was 50%, the average cost for annual FOBT was $5076. The estimated incremental cost-effectiveness ratio was $22,309 per life year saved. Using a series of sensitivity analyses, the choice of screening strategy was most sensitive to the prevalence of disease, test specificities, and participation rate. When the base-case analyses were tested over the worst and best-case scenarios, the incremental cost-effectiveness ratio varied from $32,863 to $95,668 per life year saved.<br><br>CONCLUSION: Under the most favorable conditions, immunochemical FOBT screening in renal transplant recipients appears good value for money. Uncertainties, however, exist in the model's influential estimates. Primary research into these uncertainties is necessary to confirm whether population colorectal cancer screening is cost-effective in renal transplant population.}, }
@article {pmid18316991, year = {2008}, author = {Lee, BE and Pang, XL and Robinson, JL and Bigam, D and Monroe, SS and Preiksaitis, JK}, title = {Chronic norovirus and adenovirus infection in a solid organ transplant recipient.}, journal = {The Pediatric infectious disease journal}, volume = {27}, number = {4}, pages = {360-362}, doi = {10.1097/INF.0b013e31815f5b5a}, pmid = {18316991}, issn = {0891-3668}, mesh = {Adenoviridae/*isolation &amp; purification ; Adenoviridae Infections/*virology ; Caliciviridae Infections/*virology ; Diarrhea/virology ; Feces/virology ; Humans ; Infant ; Liver Failure/*complications ; Male ; Norovirus/*isolation &amp; purification ; Transplants/*adverse effects ; }, abstract = {A 10-month-old boy developed chronic diarrhea 2 months after a combined liver, pancreas, and small bowel transplant. Norovirus and adenovirus were detected in multiple stool specimens during a 114-day period. Enteric viral infectious should be considered in solid organ transplant recipients with chronic diarrhea.}, }
@article {pmid18315917, year = {2008}, author = {Jia, JS and Huang, XJ and Liu, DH and Xiu, LP and Zhang, YC and Wu, T and Wang, JB and Su, H and Lu, QY and Lu, DP}, title = {[Relationship between Clostridium difficile associated diarrhea and intestinal microecosystem disorder in patients received allogeneic hematopoietic stem cell transplantation].}, journal = {Zhongguo shi yan xue ye xue za zhi}, volume = {16}, number = {1}, pages = {135-139}, pmid = {18315917}, issn = {1009-2137}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/*adverse effects/therapeutic use ; Child ; Clostridioides difficile/*growth &amp; development ; Clostridium Infections/*microbiology ; Diarrhea/*microbiology ; Female ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Young Adult ; }, abstract = {This study was to investigate the relationship between Clostridium difficile associated diarrhea (CDAD) and intestinal microecosystem in patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to clarify clinical characteristics of intestinal microecosystem disorder. Clostridium difficile (CD) was isolated and identified by enzyme-linked-immunosorbent assay using clostridium difficile Premier toxins A&amp;B Kit and anaerobic culture in 44 cases with diarrhea. Fecal flora (bifidobacteria, lactobacillus, bacteroides, peptostreptococcus, Clostridium perfringens, enterobacteriaceae, enterococcus, and yeasts) of patients were quantitatively and qualitatively analyzed by Mitsuoka's methods. The results showed that CDAD occurred after using antibiotic or chemotherapy. Clostridium difficile was detected in 12 patients with diarrhea (positive rate was 27.27%). There was marked changes of intestinal microecosystem when patients suffered from CDAD. The number of lactobacillus, bifidobacteria, bacteroides, enterobacteriaceae and so on decreased significantly. It was effective to treat CDAD with vancomycin, metronidazole and probiotic, but the recurrence rate was 16.67%. In conclusion, CDAD complicated by allo-HSCT is related to change of intestinal microecosystem. While treating CDAD with the sensitive antibiotic, the intestinal flora of patients should be supported actively. This treatment contributes to improving disease status and reducing diarrhea recurrence.}, }
@article {pmid18282236, year = {2008}, author = {Nicolasora, NP and Reddy, P and Kaul, DR}, title = {Biopsy-proven adenoviral diarrhea responding to low-dose cidofovir.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {10}, number = {5}, pages = {346-350}, doi = {10.1111/j.1399-3062.2008.00303.x}, pmid = {18282236}, issn = {1399-3062}, mesh = {Adenoviridae/immunology/isolation &amp; purification ; Adenovirus Infections, Human/*drug therapy/etiology/pathology ; Aged ; Antigens, Viral/isolation &amp; purification ; Antiviral Agents/*therapeutic use ; Biopsy ; Cidofovir ; Cytosine/administration &amp; dosage/*analogs &amp; derivatives/therapeutic use ; Dexamethasone/administration &amp; dosage/adverse effects ; Diarrhea/*drug therapy/pathology/virology ; Drug Administration Schedule ; Feces/virology ; Gastric Mucosa/pathology/virology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunosuppressive Agents/administration &amp; dosage/adverse effects ; Inclusion Bodies, Viral ; Intranuclear Inclusion Bodies ; Male ; Multiple Myeloma/surgery ; Organophosphonates/administration &amp; dosage/*therapeutic use ; Thalidomide/administration &amp; dosage/adverse effects ; Treatment Outcome ; }, abstract = {We present a case of diarrhea secondary to biopsy-proven adenovirus (ADV) infection after autologous peripheral hematopoietic stem cell transplant for multiple myeloma. The patient had a negative plasma polymerase chain reaction for ADV and a dramatic clinical response to low-dose cidofovir. To our knowledge, this is the first report in an adult hematopoietic stem cell recipient of the use of low-dose cidofovir to treat proven ADV gastrointestinal infection.}, }
@article {pmid18279100, year = {2008}, author = {Gai, JJ and Marks, SL}, title = {Salmon poisoning disease in two Malayan sun bears.}, journal = {Journal of the American Veterinary Medical Association}, volume = {232}, number = {4}, pages = {586-588}, doi = {10.2460/javma.232.4.586}, pmid = {18279100}, issn = {0003-1488}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Antiplatyhelmintic Agents/therapeutic use ; Doxycycline/therapeutic use ; Famotidine/therapeutic use ; Feces/parasitology ; Female ; Food Contamination ; Foodborne Diseases/diagnosis/drug therapy/*veterinary ; Malaysia ; Male ; Neorickettsia/*isolation &amp; purification ; Oxytetracycline/therapeutic use ; Parasite Egg Count/veterinary ; Praziquantel/therapeutic use ; Treatment Outcome ; Trematoda/isolation &amp; purification/*microbiology ; Trout/*microbiology/*parasitology ; *Ursidae ; }, abstract = {CASE DESCRIPTION: 2 captive sun bears (Helarctos malayanus) were evaluated because of acute onset of vomiting, mucoid diarrhea, lethargy, and anorexia 1 week after eating live trout from a northern California reservoir.<br><br>CLINICAL FINDINGS: In 1 of the bears, a CBC and serum biochemical analyses revealed mild anemia, mild eosinophilia, moderate lymphopenia, moderate hypoalbuminemia, and high serum G-glutamyltransferase activity. Ultrasonographic examination of the same bear revealed ascites and mesenteric lymphadenopathy. Histologic examination of gastrointestinal tract biopsy specimens revealed moderate to severe lymphoplasmacytic and eosinophilic gastritis, enteritis, and colitis. Ova of Nanophyetus salmincola, the trematode vector of Neorickettsia helminthoeca (a rickettsial organism that causes salmon poisoning disease), were detected in fecal samples from both bears.<br><br>TREATMENT AND OUTCOME: The bears were treated with oxytetracycline, doxycycline, praziquantel, and famotidine. Within 1 week after initiation of treatment, the appetite and fecal consistency of each bear were considered normal. Fecal ova shedding began 4 days after onset of clinical signs and ceased 9 days later.<br><br>CLINICAL RELEVANCE: Salmon poisoning disease can be rapidly fatal in untreated animals, but if diagnosed early and treated appropriately, full recovery can be achieved. Domestic dogs and captive exotic bears are highly susceptible to clinical disease after ingestion of trematode-infected fish. Salmon poisoning disease may develop outside the geographic range in which the causative organism is endemic as a result of the transplantation of infected fish for sport fishing; veterinarians practicing in areas where infected fish may be transplanted should be aware of appropriate diagnostic and treatment protocols.}, }
@article {pmid18261038, year = {2008}, author = {Spahn, TW and Ross, M and von Eiff, C and Maaser, C and Spieker, T and Kannengiesser, K and Domschke, W and Kucharzik, T}, title = {CD4+ T cells transfer resistance against Citrobacter rodentium-induced infectious colitis by induction of Th 1 immunity.}, journal = {Scandinavian journal of immunology}, volume = {67}, number = {3}, pages = {238-244}, doi = {10.1111/j.1365-3083.2007.02063.x}, pmid = {18261038}, issn = {1365-3083}, mesh = {*Adoptive Transfer ; Animals ; Antibodies, Bacterial/blood ; CD4-Positive T-Lymphocytes/immunology/*transplantation ; Citrobacter rodentium/immunology ; Colitis/immunology/microbiology/*prevention &amp; control ; Enterobacteriaceae Infections/immunology/pathology/*prevention &amp; control ; Female ; Flow Cytometry ; Immunoglobulin A/analysis/immunology ; Interferon-gamma/metabolism ; Interleukin-10/metabolism ; Interleukin-17/metabolism ; Interleukin-2/metabolism ; Mice ; Mice, Inbred BALB C ; Th1 Cells/*immunology ; }, abstract = {Citrobacter rodentium induces an acute, self-limited colitis in mice which is histologically associated with crypt hyperplasia. The infection serves as a model for human infectious colitis induced by enteropathogenic Escherichia coli. We investigated if Balb/c mice, which had spontaneously cleared C. rodentium infection, were protected against re-infection and if resistance against intestinal infection can be systemically transferred using spleen cells. The course of infection was monitored by faecal excretion. Spleen cells, splenic CD3+ and CD4+ cells were transferred from resistant mice to non-infected recipients prior to infection. Cytokine secretion, serum and faecal antibody titres and histological disease severity were assessed. Balb/c mice were resistant against re-infection. The course of infection was shorter in mice receiving primed spleen cells, CD3+ and CD4+ cells. Transfer of CD4+ T cells from resistant mice induced gamma-interferon, interleukin (IL)-2 and IL-17 secretion and suppressed IL-10 secretion. Anti-Citrobacter serum IgG1 and IgG2a enzyme-linked immunosorbent assay OD levels were increased. Faecal IgA secretion was increased while serum IgA was suppressed in recipients of CD4+ cells. Large bowel histology showed protection from colitis in recipients of primed cells as indicated by normal colonic epithelium. In Balb/c mice, C. rodentium infection is followed by resistance, which can be transferred by CD4+ cells. Transfer of protection is associated with IL-17 secretion, enhanced serum IgG and faecal IgA secretion. This is the first study to demonstrate the mechanisms by which systemic resistance from previously C. rodentium-infected mice can be transferred to non-infected animals.}, }
@article {pmid18248870, year = {2008}, author = {Katoh, M and Tateno, C and Yoshizato, K and Yokoi, T}, title = {Chimeric mice with humanized liver.}, journal = {Toxicology}, volume = {246}, number = {1}, pages = {9-17}, doi = {10.1016/j.tox.2007.11.012}, pmid = {18248870}, issn = {0300-483X}, mesh = {Adrenergic Agents/blood/*pharmacokinetics ; Animals ; Anti-Bacterial Agents/*pharmacokinetics ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases/genetics ; Cefmetazole/*pharmacokinetics ; Cytochrome P-450 CYP2A6 ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System/*metabolism/physiology ; Debrisoquin/analogs &amp; derivatives/blood/metabolism/*pharmacokinetics ; Drug Interactions ; Enzyme Induction ; Hepatocytes/cytology/*metabolism/transplantation ; Humans ; *Liver/drug effects/enzymology/metabolism ; Male ; Mice ; Mixed Function Oxygenases/genetics ; Models, Biological ; Polymorphism, Genetic ; Species Specificity ; Transplantation Chimera/*metabolism ; }, abstract = {Recently, chimeric mice with humanized liver were established by transplanting human hepatocytes into an urokinase-type plasminogen activator(+/+)/severe combined immunodeficient transgenic mouse line. The replacement with human hepatocytes is more than 80-90% and is higher than any other chimeric mouse reported previously. In drug development, the liver is one of the most important organs because it is mainly involved in the pharmacokinetics of drugs and is frequently damaged by many drugs due to the accumulation of drugs and/or metabolites. The pharmacokinetics could affect the efficacy and toxicity of a drug, and thus prediction of the human pharmacokinetics is important for developing new drugs without adverse reactions and toxicity. Extrapolation from experimental animals or in vitro studies to the human in vivo pharmacokinetics is still difficult. To date, human hepatocytes and liver microsomes are recognized as better tools and are frequently used to estimate the human pharmacokinetics. We thought that chimeric mice with humanized liver could become a new tool for estimating the human toxicity and pharmacokinetics. At first, metabolism, which plays an essential role in pharmacokinetics, was investigated in the chimeric mice. In the liver of the chimeric mice, human drug metabolizing enzymes were found to be expressed and to reflect the capacities and genetic polymorphism of the donor. In an in vivo study on metabolism, human specific metabolites could be detected in the serum of the chimeric mice indicating that the chimeric mice could be used as an in vivo model to address human metabolism. These results suggested that the chimeric mice could overcome the species differences in drug metabolism and be used to evaluate drug toxicity due to genetic polymorphism. The reasons for drug interaction are often enzyme induction and inhibition. By the treatment with a typical inducer of cytochrome P450 (P450), which is the central drug-metabolizing enzyme, P450s expressed in the liver of the chimeric mice were found to possess induction potencies. After the treatment with a specific inhibitor of human P450, the area under the curve of the P450 metabolite was significantly decreased in the chimeric mice but not in the control mice. Therefore, it was indicated that the chimeric mice could be useful for assessing drug interactions in vivo. Moreover, drug excretion was determined to be humanized because cefmetazole was mainly excreted in urine both in the chimeric mice and humans but in the feces in control uPA(-/-)/SCID mice. Drug transporters expressed in the liver of the chimeric mice were also humanized. In this review, studies of the chimeric mice with humanized liver, particularly on metabolism and excretion, are summarized and the possibility of using the chimeric mice is proposed for the advanced prediction of human pharmacokinetics and toxicity.}, }
@article {pmid18236387, year = {2008}, author = {Cooper, SC and Olliff, SP and McCafferty, I and Wigmore, SJ and Mirza, DF}, title = {Polyarteritis nodosa, presenting as life-threatening gastrointestinal hemorrhage in a liver transplant recipient.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {14}, number = {2}, pages = {151-154}, doi = {10.1002/lt.21283}, pmid = {18236387}, issn = {1527-6465}, mesh = {Autoimmune Diseases/complications/diagnostic imaging/*surgery ; Carcinoma, Hepatocellular/complications/surgery ; Endoscopy, Gastrointestinal ; Female ; Gastrointestinal Hemorrhage/complications/diagnostic imaging/drug therapy/*etiology ; Hematemesis/etiology ; *Hepatic Artery/diagnostic imaging/surgery ; Humans ; Liver Cirrhosis/complications/diagnostic imaging/*surgery ; Liver Neoplasms/complications/surgery ; Liver Transplantation/*adverse effects ; Melena/etiology ; Middle Aged ; Polyarteritis Nodosa/complications/*diagnosis/drug therapy/etiology ; Portal Vein/surgery ; Radiography ; Rectum ; Reoperation ; Steroids/therapeutic use ; Treatment Outcome ; Venous Thrombosis/complications/surgery ; }, abstract = {This unique case reports the first recorded episode in the medical literature of vasculitis post-liver transplantation, presenting as life-threatening gastrointestinal hemorrhage. A 52-year-old Caucasian woman underwent orthotopic liver transplantation (OLT) for autoimmune cirrhosis complicated by hepatoma and portal vein thrombosis. Late hepatic artery thrombosis led to a second liver graft. Following recovery from an episode of acute rejection, the patient presented with large volume hematemesis, melena, and hemochezia (passage of fresh blood from the rectum). Following upper and lower gastrointestinal endoscopy and surgery, angiography illustrated the presence of polyarteritis nodosa (PAN), which was successfully treated with high-dose steroid therapy. Gastrointestinal hemorrhage is an unusual presentation of vasculitis, especially PAN. The occurrence of this phenomenon post-OLT, in the presence of immunosuppression is previously unreported.}, }
@article {pmid18204878, year = {2008}, author = {Altomare, DF and La Torre, F and Rinaldi, M and Binda, GA and Pescatori, M}, title = {Carbon-coated microbeads anal injection in outpatient treatment of minor fecal incontinence.}, journal = {Diseases of the colon and rectum}, volume = {51}, number = {4}, pages = {432-435}, doi = {10.1007/s10350-007-9170-7}, pmid = {18204878}, issn = {0012-3706}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Carbon ; *Coated Materials, Biocompatible ; Defecation ; Fecal Incontinence/physiopathology/psychology/*therapy ; Female ; Follow-Up Studies ; Glucans/administration &amp; dosage ; Humans ; Injections ; Male ; *Microspheres ; Middle Aged ; Patient Satisfaction ; Quality of Life ; Time Factors ; Treatment Outcome ; Zirconium/administration &amp; dosage ; }, abstract = {PURPOSE: Anal bulking agents are injected to pose a stronger obstacle to the involuntary passage of feces and gas. This prospective, multicenter study was designed to evaluate the safety and efficacy of Durasphere anal injection for the treatment of fecal incontinence.<br><br>PATIENTS AND METHODS: Thirty-three unselected patients with incontinence (24 females; mean age, 61.5 +/- 14 (range, 22-83) years) underwent anal bulking agent submucosal injection with carbon-coated microbeads (Durasphere) in the outpatient regimen. The causes of incontinence were obstetric lesions in 18.2 percent, iatrogenic in 36.4 percent, rectal surgery in 12.1 percent, and idiopathic in 33.3 percent. Previous unsuccessful treatments for fecal incontinence included diet and drugs in 16 patients, biofeedback training in 7 patients, sacral nerve modulation in 6 patients, sphincteroplasty in 2 patients, artificial bowel sphincter in 1 patient, and PTQ macroplastique bulking agent in 1 patient. Under local anesthesia and antibiotic prophylaxis, a mean of 8.8 (range, 2-19) ml of Durasphere were injected into the submucosa by using a 1.5-inch, angled, 18-gauge needle.<br><br>RESULTS: After a median follow-up of 20.8 (range, 10-22) months, the median Cleveland Clinic continence score decreased significantly from 12 to 8 (P < 0.001) and the median American Medical System score from 89 to 73 (P = 0.0074), but the Fecal Incontinence Quality of Life did not change significantly (74 to 76, P = not significant). Anal manometry significantly improved (resting pressure increasing from 34 to 42 mmHg; P = 0.008) and squeezing pressure from 66 to 79 mmHg (P = 0.04). Two patients complained of moderate anal pain for a few days after the implant, one patient had asymptomatic leakage of the injected material through a mucosa perforation, and two had distal migration of the Durasphere along the dentate line.<br><br>CONCLUSIONS: Anal bulking agent injection is a safe treatment and can mitigate the severity of fecal incontinence by increasing anal pressure but does not significantly improve the quality of life.}, }
@article {pmid18190324, year = {2007}, author = {Nagappan, V and Deresinski, S}, title = {Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {45}, number = {12}, pages = {1610-1617}, doi = {10.1086/523576}, pmid = {18190324}, issn = {1537-6591}, mesh = {Animals ; Antifungal Agents/chemistry/*pharmacology/therapeutic use ; Candidiasis/drug therapy ; Controlled Clinical Trials as Topic ; Disease Models, Animal ; Fungi/drug effects ; Humans ; Microbial Sensitivity Tests ; Mycoses/prevention &amp; control ; Triazoles/chemistry/*pharmacology/therapeutic use ; }, abstract = {Posaconazole is a triazole antifungal agent with a spectrum of activity that includes Candida and Cryptococcus species, many molds, and some endemic fungi. Posaconazole has received US Food and Drug Administration approval for the treatment of oropharyngeal candidiasis, including infections refractory to itraconazole and/or fluconazole. It is also approved as prophylaxis for invasive Aspergillus and Candida infections in patients aged >or=13 years who are at high risk of developing these infections, in adult and adolescent hematopoietic stem cell transplant recipients with graft-versus-host disease, and in persons with hematologic malignancies and prolonged neutropenia due to chemotherapy, who are at high risk of developing these infections. Approval for additional indications is being sought. Limited clinical experience suggests efficacy for the treatment of infections due to Zygomycetes and as salvage therapy for patients with invasive aspergillosis and coccidioidomycosis. Currently available only as an oral suspension, posaconazole, which has been well tolerated, requires administration with food or a nutritional supplement to assure adequate bioavailability. Posaconazole is predominantly eliminated in the feces, where it appears as unchanged drug. Metabolism, mostly glucuronidation, plays only a minor role in its elimination, as does renal clearance; as a consequence, dose adjustment is not required in the presence of renal or hepatic insufficiency. Although not a substrate of hepatic CYP450 3A4, posaconazole inhibits this enzyme and thus has the potential for significant pharmacokinetic interactions with drugs metabolized by this isoform. Its use in combination with CYP450 substrates that prolong the QTc interval is contraindicated, as is its use with ergot alkaloids; administration of posaconazole with other substrates and/or inducers of this enzyme system requires caution. Posaconazole is both a substrate and inhibitor of P-glycoprotein. Currently, the major roles for posaconazole in clinical practice are as prophylaxis for neutropenic patients with significant risk of infection with filamentous fungi and as therapy for zygomycoses. It may also have a role in the treatment of other filamentous fungal and some yeast infections, but assessment of its overall place in antifungal therapy awaits the availability of further clinical experience.}, }
@article {pmid18161771, year = {2008}, author = {Kruszyna, T and Walsh, M and Peltekian, K and Molinari, M}, title = {Early invasive Listeria monocytogenes infection after orthotopic liver transplantation: case report and review of the literature.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {14}, number = {1}, pages = {88-91}, doi = {10.1002/lt.21428}, pmid = {18161771}, issn = {1527-6465}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Cholangitis, Sclerosing/*surgery ; Follow-Up Studies ; Humans ; Laparotomy ; Listeria monocytogenes/*isolation &amp; purification ; Listeriosis/drug therapy/*microbiology/surgery ; *Liver Transplantation ; Male ; Peritonitis/drug therapy/*microbiology/surgery ; Postoperative Complications ; }, abstract = {Infection with Listeria monocytogenes is rare, with a reported annual incidence of 4.4 cases per million individuals. It is caused by a gram-positive rod-shaped bacterium (Listeria monocytogenes) that can be found in soil, vegetation, water, sewage, and silage and in feces of humans and animals. It is a facultative intracellular pathogen with the ability to survive and multiply in phagocytic host cells, even in adverse environmental circumstances. Listeriosis has rarely been reported after orthotopic liver transplantation, and transplant physicians are often unfamiliar with the clinical presentation of this rare but virulent infection, which accounts for 20%-30% mortality in affected individuals. We present a case of invasive Listeria infection causing bacteremia and peritonitis in the early postoperative period after cadaveric liver transplantation in a previously asymptomatic patient.}, }
@article {pmid18158950, year = {2008}, author = {Liu, S and Kim, YS and Hsieh, WY and Gupta Sreerama, S}, title = {Coligand effects on the solution stability, biodistribution and metabolism of the (99m)Tc-labeled cyclic RGDfK tetramer.}, journal = {Nuclear medicine and biology}, volume = {35}, number = {1}, pages = {111-121}, pmid = {18158950}, issn = {0969-8051}, support = {R21 HL083961/HL/NHLBI NIH HHS/United States ; R01 CA115883/CA/NCI NIH HHS/United States ; R21 EB003419/EB/NIBIB NIH HHS/United States ; 1R01 CA115883-01A2/CA/NCI NIH HHS/United States ; R21 HL083961-02/HL/NHLBI NIH HHS/United States ; R21 EB003419-02/EB/NIBIB NIH HHS/United States ; R01 CA115883-01A2/CA/NCI NIH HHS/United States ; R21 HL083961-01/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Chromatography, High Pressure Liquid ; Female ; Humans ; Ligands ; Mice ; Neoplasm Transplantation ; Neoplasms, Experimental/diagnostic imaging/*metabolism ; *Organotechnetium Compounds ; Peptides, Cyclic/*metabolism ; Radionuclide Imaging ; Radiopharmaceuticals/*metabolism ; Tissue Distribution ; Transplantation, Heterologous ; }, abstract = {In this study, we present the evaluation of two new ternary ligand (99m)Tc complexes [(99m)Tc(HYNIC tetramer)(tricine)(L)] [L=isonicotinic acid (ISONIC) and 2,5-pyridinedicarboxylic acid (PDA)] as potential radiotracers for tumor imaging. Athymic nude mice bearing MDA-MB-435 human breast cancer xenografts were used to evaluate their biodistribution and metabolic properties. Solution stability data showed that [(99m)Tc(HYNIC tetramer)(tricine)(L)] (L=ISONIC and PDA) had significant decomposition (14% and 35%, respectively) at 6 h in the absence of excess ISONIC or PDA coligand. Biodistribution data clearly showed that [(99m)Tc(HYNIC tetramer)(tricine)(PDA)] had a much lower uptake in most organs of interest than [(99m)Tc(HYNIC tetramer)(tricine)(ISONIC)] during the 2-h study period. Results from metabolism studies revealed that approximately 50% of [(99m)Tc(HYNIC tetramer)(tricine)(ISONIC)] remained intact in fecal samples at 120 min postinjection, whereas only 10% of [(99m)Tc(HYNIC tetramer)(tricine)(PDA)] remained intact in fecal samples. The extent of metabolism correlated well with radiotracer solution stability. The results from this and our previous studies clearly demonstrated that coligands [trisodium triphenylphosphine-3,3',3''-trisulfonate (TPPTS), ISONIC and PDA] have a significant impact on the tumor uptake, excretion kinetics and metabolism of the (99m)Tc-labeled cyclic RGDfK tetramer. Among the three radiotracers evaluated in this tumor-bearing animal model, [(99m)Tc(HYNIC tetramer)(tricine)(TPPTS)] remained the best with respect to blood clearance, tumor uptake and target/background ratios.}, }
@article {pmid18089357, year = {2007}, author = {Pawłowska, J and Klewicka, E and Czubkowski, P and Motyl, I and Jankowska, I and Libudzisz, Z and Teisseyre, M and Gliwicz, D and Cukrowska, B}, title = {Effect of Lactobacillus casei DN-114001 application on the activity of fecal enzymes in children after liver transplantation.}, journal = {Transplantation proceedings}, volume = {39}, number = {10}, pages = {3219-3221}, doi = {10.1016/j.transproceed.2007.03.101}, pmid = {18089357}, issn = {0041-1345}, mesh = {Adolescent ; Cellulases/metabolism ; Child ; Child, Preschool ; Feces/*enzymology/*microbiology ; Female ; Glucuronidase/metabolism ; Humans ; *Lacticaseibacillus casei ; Liver Transplantation/*physiology ; Male ; Placebos ; Urease/metabolism ; }, abstract = {Immunosuppressive and antibacterial regimens in children after liver transplantation create a gut microflora imbalance that can be indirectly measured by the activity of fecal enzymes. The aim of this study was to specify the influence of diet supplementation with probiotic Lactobacillus casei DN on the activity of beta-glucuronidase, beta-glucosidase, and urease. Twenty-five children after liver transplantation (13 girls, 12 boys) ages 3 to 17 years were enrolled in the study. Two months after bacteria application the levels of all 3 enzymes decreased, reaching statistical significance for beta-glucuronidase and beta-glucosidase. Complete rebound in enzyme activity was observed months after the end of probiotic supplementation. We concluded that Lactobacillus casei DN-114001 consumption decreased fecal enzyme activity, a beneficial effect limited to the period of bacteria intake.}, }
@article {pmid18084771, year = {2008}, author = {Fürst, A and Schmidbauer, C and Swol-Ben, J and Iesalnieks, I and Schwandner, O and Agha, A}, title = {Gracilis transposition for repair of recurrent anovaginal and rectovaginal fistulas in Crohn's disease.}, journal = {International journal of colorectal disease}, volume = {23}, number = {4}, pages = {349-353}, pmid = {18084771}, issn = {0179-1958}, mesh = {Adult ; Crohn Disease/*complications/surgery ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Muscle, Skeletal/*transplantation ; Prospective Studies ; Plastic Surgery Procedures/*methods ; Rectovaginal Fistula/etiology/*surgery ; Recurrence ; Treatment Outcome ; }, abstract = {OBJECTIVE: Local surgical procedures in the presence of Crohn's disease have a markedly reduced success rate, especially in the treatment of recurrent anovaginal and distant rectovaginal fistulas. In these patients, local surgery (e.g., flap closure) has unsatisfactory results if the anal canal is destroyed by ulceration and indurations or in patients with extensive defects of the perineum.<br><br>MATERIALS AND METHODS: Over a period of 6 years (2000 to 2006), 12 patients with recurrent rectovaginal fistulas were treated with graciloplasty. The age of the female patients ranged from 24 to 47 years, the mean age being 38 years. The presence of Crohn's disease in all patients had a mean duration of 12 years. Corticosteroids, mesalazin, or azathioprin were administered preoperatively. All patients were diverted by a temporary ileostomy before graciloplasty. RESULTS Rectovaginal fistula was closed in 11 of 12 patients after graciloplasty with a mean follow-up of 3.4 years. One rerecurrence of a rectovaginal fistula was documented. One of 12 ileostomies was not closed due to persistence of the fistula tract. One patient had a pouch-anal and, additionally, a pouch-vaginal fistula. In this patient, the first transposition of the gracilis muscle was unsuccessful. After a few months, she underwent renewed graciloplasty. There was no recurrence of a fistula within the follow-up period. Reconstruction of the perineum constituted an additional positive effect of the graciloplasty. In one patient, the preexisting fecal incontinence persisted, even after secondary implantation of a pacemaker. Due to diarrhea and persistent fecal incontinence, the patient opted for a renewed ileostomy.<br><br>CONCLUSIONS: In our series, gracilis transposition in the treatment of recurrent anovaginal and rectovaginal fistulas in patients with Crohn's disease has excellent short-term results. In addition, graciloplasty can reconstruct the perineal defect.}, }
@article {pmid18063537, year = {2007}, author = {Hooker, M}, title = {Clostridium difficile.}, journal = {Clinical journal of oncology nursing}, volume = {11}, number = {6}, pages = {801-804}, doi = {10.1188/07.CJON.801-804}, pmid = {18063537}, issn = {1092-1095}, mesh = {Anti-Infective Agents/therapeutic use ; Anti-Inflammatory Agents/adverse effects ; Beclomethasone/adverse effects ; Biopsy ; Budesonide/adverse effects ; *Clostridioides difficile/physiology/ultrastructure ; Colonoscopy ; *Enterocolitis, Pseudomembranous/diagnosis/etiology/therapy ; Feces/microbiology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunosuppressive Agents/*adverse effects ; Infection Control/methods ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Oncology Nursing ; Primary Myelofibrosis/therapy ; Risk Factors ; Tacrolimus/adverse effects ; Vancomycin/therapeutic use ; }, abstract = {George, a 55-year-old retired businessman with a diagnosis of myelofibrosis, underwent an allogeneic stem cell transplantation from his human leukocyte antigen-matched brother in June 2006. He was admitted to the hospital for a possible flare of graft-versus-host disease (GVHD) of the gut. His medications included tacrolimus, budesonide, and bechlamethasone for immunosuppression and pantoprazole. A stool sample was positive for Clostridium difficile toxin A on October 31, 2006, and he was started on oral metronidazole.}, }
@article {pmid18056760, year = {2008}, author = {Tchoua, U and D'Souza, W and Mukhamedova, N and Blum, D and Niesor, E and Mizrahi, J and Maugeais, C and Sviridov, D}, title = {The effect of cholesteryl ester transfer protein overexpression and inhibition on reverse cholesterol transport.}, journal = {Cardiovascular research}, volume = {77}, number = {4}, pages = {732-739}, doi = {10.1093/cvr/cvm087}, pmid = {18056760}, issn = {0008-6363}, mesh = {ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters/genetics/metabolism ; Animals ; Anticholesteremic Agents/*pharmacology ; Cell Line ; Cholesterol/blood/*metabolism ; Cholesterol Ester Transfer Proteins/*antagonists &amp; inhibitors/genetics/*metabolism ; Cholesterol Esters/metabolism ; Cholesterol, HDL/metabolism ; Cholesterol, LDL/metabolism ; Cholesterol, VLDL/metabolism ; Cricetinae ; Dose-Response Relationship, Drug ; Feces/chemistry ; Humans ; Liver/drug effects/metabolism ; Macrophages/*drug effects/*metabolism/transplantation ; Mice ; Quinolines/*pharmacology ; Time Factors ; Transfection ; Triglycerides/metabolism ; Up-Regulation ; }, abstract = {AIMS: Cholesteryl ester transfer protein (CETP) has a well-established role in lipoprotein metabolism, but the effect of its overexpression or inhibition on the efficiency of reverse cholesterol transport (RCT) is unclear.<br><br>METHODS AND RESULTS: Neither overexpression of CETP nor treatment with CETP inhibitor Torcetrapib of RAW 264.7 macrophages or HepG2 hepatocytes affected cholesterol efflux in vitro. Overexpression of CETP or treatment with Torcetrapib, respectively, stimulated or inhibited HDL cholesteryl ester uptake by HepG2 but not by RAW 264.7 cells. When RAW 264.7 cells transfected with CETP or ATP binding cassette transporter A1 (ABCA1) were injected intraperitoneally into mice, cholesterol egress from macrophages was elevated for ABCA1- but not for CETP-transfected macrophages. Systemic expression of CETP in mice by adenoviral infection stimulated egress of cholesterol to plasma and liver without affecting HDL levels. Treatment with Torcetrapib did not affect appearance of macrophage cholesterol in plasma and liver, but inhibited its excretion into feces. Treatment of hamsters with Torcetrapib led to elevation of HDL cholesterol, an increase in the capacity of plasma to support cholesterol efflux, and increased egress of cholesterol from macrophages to plasma and feces in vivo.<br><br>CONCLUSION: Both increased (mice study) and decreased (hamster study) CETP activity could result in enhanced RCT.}, }
@article {pmid18047566, year = {2008}, author = {Siu, YP and Tong, MK and Kwok, YL and Leung, KT and Kwan, TH and Lam, CS and Au, TC}, title = {An unusual case of both upper and lower gastrointestinal bleeding in a kidney transplant recipient.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {10}, number = {4}, pages = {276-279}, doi = {10.1111/j.1399-3062.2007.00286.x}, pmid = {18047566}, issn = {1399-3062}, mesh = {Fatal Outcome ; Gastrointestinal Hemorrhage/*microbiology ; Humans ; *Ileal Diseases/diagnosis/microbiology/physiopathology ; Ileum/microbiology/physiopathology/surgery ; Kidney Transplantation/*adverse effects ; Laparotomy ; Male ; Melena/microbiology ; Middle Aged ; *Tuberculosis, Gastrointestinal/diagnosis/microbiology/physiopathology ; }, abstract = {BACKGROUND: Tuberculosis (TB) is an uncommon opportunistic infection in immunocompromised patients. Extrapulmonary infection involving the intestine is rare and poses diagnostic difficulties.<br><br>CASE REPORT: A 49-year-old man with IgA nephropathy underwent a kidney transplantation in 1996 and was put on cyclosporine, azathioprine, and steroid. He suffered from a recurrence of his primary kidney disease and had a gradual deterioration of renal function since 1998. By 2005, he presented with an unusual gastrointestinal (GI) symptom with alternating signs of upper GI bleeding - melena - as well as lower GI bleeding with fresh rectal bleeding, resulting in severe anemia with hemoglobin level down to 5.0 g/dL. At the same time, his renal function further deteriorated and necessitated the initiation of dialysis while he was maintained on low-dose immunosuppressive drugs. Repeated upper and lower GI endoscopies were either unremarkable or revealed non-specific lesions. Symptoms persisted and exploratory laparotomy finally showed a 1 cm submucosal mass at the proximal jejunum and multiple inflammatory lesions at the terminal ileum. Segmental resection of the lesions was performed and confirmed TB infection. However, despite the initiation of anti-tuberculous treatment, the patient eventually died of complications.<br><br>CONCLUSION: Diagnosing TB intestinal infection is a clinical challenge. A high index of suspicion in susceptible subjects is necessary, and early surgical intervention should always be considered when facing diagnostic uncertainties.}, }
@article {pmid18043625, year = {2007}, author = {Pang, X and Hua, X and Yang, Q and Ding, D and Che, C and Cui, L and Jia, W and Bucheli, P and Zhao, L}, title = {Inter-species transplantation of gut microbiota from human to pigs.}, journal = {The ISME journal}, volume = {1}, number = {2}, pages = {156-162}, doi = {10.1038/ismej.2007.23}, pmid = {18043625}, issn = {1751-7362}, mesh = {Animals ; Animals, Newborn ; Bacteria/classification/genetics/isolation &amp; purification ; Bacteroides/classification/genetics/isolation &amp; purification ; Bifidobacterium/classification/genetics/isolation &amp; purification ; Child ; DNA Fingerprinting/methods ; Electrophoresis, Polyacrylamide Gel ; Gastrointestinal Tract/*microbiology ; Germ-Free Life ; Humans ; Male ; *Models, Animal ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Species Specificity ; Swine ; }, abstract = {Direct research on gut microbiota for understanding its role as 'an important organ' in human individuals is difficult owing to its vast diversity and host specificity as well as ethical concerns. Transplantation of human gut microbiota into surrogate hosts can significantly facilitate the research of human gut ecology, metabolism and immunity but rodents-based model provides results with low relevance to humans. A new human flora-associated (HFA) piglet model was hereby established taking advantage of the high similarity between pigs and humans with respect to the anatomy, physiology and metabolism of the digestive system. Piglets were delivered via cesarean section into a SPF-level barrier system and were inoculated orally with a whole fecal suspension from one healthy 10-year-old boy. The establishment and composition of the intestinal microbiota of the HFA piglets were analyzed and compared with that of the human donor using enterobacterial repetitive intergenic consensus sequence-PCR fingerprinting-based community DNA hybridization, group-specific PCR-temperature gradient gel electrophoresis and real-time PCR. Molecular profiling demonstrated that transplantation of gut microbiota from a human to germfree piglets produced a donor-like microbial community with minimal individual variation. And the microbial succession with aging of those ex-germfree piglets was also similar to that observed in humans. This HFA model provides a significantly improved system for research on gut ecology in human metabolism, nutrition and drug discovery.}, }
@article {pmid18035188, year = {2007}, author = {Schiller, DS and Fung, HB}, title = {Posaconazole: an extended-spectrum triazole antifungal agent.}, journal = {Clinical therapeutics}, volume = {29}, number = {9}, pages = {1862-1886}, doi = {10.1016/j.clinthera.2007.09.015}, pmid = {18035188}, issn = {0149-2918}, mesh = {AIDS-Related Opportunistic Infections/drug therapy ; Administration, Oral ; Antifungal Agents/administration &amp; dosage/adverse effects/pharmacology/therapeutic use ; Aspergillosis/drug therapy ; Candidiasis/drug therapy ; Drug Resistance, Fungal ; Graft vs Host Disease/drug therapy ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Mycoses/*drug therapy ; Tissue Distribution ; Triazoles/administration &amp; dosage/adverse effects/pharmacology/*therapeutic use ; }, abstract = {BACKGROUND: The incidence of invasive fungal infections (IFIs) caused by opportunistic filamentous molds is increasing, along with emerging fungal resistance. Posaconazole, a structural analogue of itraconazole that was approved for marketing in the United States in 2006, appears to be a promising antifungal agent.<br><br>OBJECTIVE: This article provides an overview of the pharmacology, efficacy, and tolerability of posaconazole when used for the prophylaxis and treatment of various common and rare fungal infections.<br><br>METHODS: Relevant information was identified through a search of MEDLINE (1966-April 2007), International Pharmaceutical Abstracts (1970-April 2007), and abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy using the terms posaconazole and SCH 56592. Additional resources were found by searching the reference lists of the identified articles and the US Food and Drug Administration Web site.<br><br>RESULTS: Posaconazole is available as an oral suspension. It is highly distributed to various sites, including bone, the central nervous system, and eye tissue. Its Vd is 2447 L when administered in multiple daily doses (up to 800 mg/d) in the presence of a high-fat meal. Because it is excreted mostly as unchanged drug in the feces (77%), posaconazole can be administered to patients with poor renal function without any dose adjustment. Posaconazole has shown in vitro and in vivo activity against a wide variety of fungi, including those that are rare and relatively resistant. Two clinical trials have compared posaconazole with fluconazole or itraconazole for the prophylaxis of IFIs in immunocompromised patients. The first, a randomized, double-blind trial in 600 recipients of hematopoietic stem cell transplants, found that overall rates of IFI did not differ significantly between posaconazole and fluconazole (5% vs 9%, respectively). The other, a randomized, open-label trial in 602 neutropenic patients, reported significantly fewer IFIs in patients receiving posaconazole compared with those receiving fluconazole or itraconazole (>2% vs >8%, respectively; P = 0.001). An additional 2 trials have investigated posaconazole for the treatment of oropharyngeal candidiasis (OPC) in patients with HIV infection. A randomized, controlled, evaluator-blinded study in 350 HIV-infected patients with OPC found similar 14-day clinical success rates with posaconazole and fluconazole (91.7% and 92.5%, respectively; 95% CI, -6.6l to 5.04), whereas an open-label study in 176 HIV-infected patients with a history of refractory OPC reported a 28-day clinical success rate of 75%. Numerous small studies and case reports have described successful posaconazole treatment of zygomycosis, aspergillosis, fusariosis, endemic dimorphic fungal infection, and superficial and subcutaneous fungal infections that were refractory to conventional antifungal agents or in patients who were unable to tolerate these agents. Posaconazole has been well tolerated. The most common complaints have been gastrointestinal in nature, including nausea (7%-8%) and diarrhea (3%-11%), although these have rarely led to permanent discontinuation of therapy. Other common adverse effects have included vomiting (4%-7%), headache (2%-8%), and liver enzyme elevations (2%-3%).<br><br>CONCLUSIONS: Posaconazole suspension administered at up to 800 mg/d is a reasonable alternative to conventional antifungal agents for the prevention and treatment of IFIs in high-risk populations. It may also be suitable in patients with infections caused by rare or relatively resistant fungi, and those who are unable to tolerate long-term therapy with other antifungal agents.}, }
@article {pmid18022427, year = {2007}, author = {Wales, PW and de Silva, N and Langer, JC and Fecteau, A}, title = {Intermediate outcomes after serial transverse enteroplasty in children with short bowel syndrome.}, journal = {Journal of pediatric surgery}, volume = {42}, number = {11}, pages = {1804-1810}, doi = {10.1016/j.jpedsurg.2007.07.029}, pmid = {18022427}, issn = {1531-5037}, mesh = {Adolescent ; Child, Preschool ; Digestive System Surgical Procedures/*methods ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Intestinal Absorption/physiology ; Intestine, Small/physiopathology/surgery ; Male ; Probability ; Retrospective Studies ; Risk Assessment ; Severity of Illness Index ; Short Bowel Syndrome/*diagnosis/*surgery ; Surgical Stapling ; Treatment Outcome ; }, abstract = {BACKGROUND: Serial transverse enteroplasty (STEP) is a novel intestinal lengthening procedure introduced in 2003. To date, no human studies exist that report objective assessment of intestinal absorptive capacity. The aim of this study was to report intermediate outcomes in patients who have received the STEP at our institution using clinical and biochemical assessment of intestinal function.<br><br>METHODS: All 14 patients who received the STEP since May 2003 were reviewed. Clinical (weight gain, enteral tolerance, stool frequency) and biochemical (citrulline levels, D-xylose absorption, alpha-1 antitrypsin clearance, and fecal fat content) outcomes were performed pre-STEP and post-STEP at 1, 6, and 12 months, respectively. Data are presented as means with standard deviation. Paired t tests were used to compare post-STEP outcomes with pre-STEP values (P < .05 was significant). Three patients had a STEP as a newborn and are analyzed separately.<br><br>MAIN RESULTS: There were 14 patients (3 females; mean age, 24.8 months; range, 1 day-14 years). Serial transverse enteroplasty resulted in a mean increase in length of dilated bowel segment of 94% +/- 30% and increase in total small bowel length of 49% +/- 42% with mean application of 16 +/- 9 cartridges and cost of Can$2878.51 +/- 1406.22. Patients demonstrated improvement in both clinical parameters, as well as intestinal absorptive function. Complications included 2 patients with staple line leak and 1 patient with gastrointestinal bleeding from staple line ulcers. Three patients died (2 from liver failure and 1 from sepsis and congenital heart disease). Two patients received liver-intestinal transplants at 4 and 5 months post-STEP. Mean follow-up was 23 +/- 9 months, with 7 patients followed more than 2 years. Of 8 patients with post-STEP follow-up of more than 1 year, 7 have weaned from parenteral nutrition.<br><br>CONCLUSION: Clinical and objective biochemical outcomes of intestinal function after the STEP procedure show promise after intermediate follow-up.}, }
@article {pmid18021993, year = {2007}, author = {Kawecki, D and Chmura, A and Pacholczyk, M and Lagiewska, B and Adadynski, L and Wasiak, D and Malkowski, P and Sawicka-Grzelak, A and Rokosz, A and Szymanowska, A and Swoboda-Kopec, E and Wroblewska, M and Rowinski, W and Durlik, M and Paczek, L and Luczak, M}, title = {Detection of Clostridium difficile in stool samples from patients in the early period after liver transplantation.}, journal = {Transplantation proceedings}, volume = {39}, number = {9}, pages = {2812-2815}, doi = {10.1016/j.transproceed.2007.08.047}, pmid = {18021993}, issn = {0041-1345}, mesh = {Adult ; Aged ; Bacterial Toxins/analysis ; Clostridioides difficile/*isolation &amp; purification ; Cross Infection/epidemiology/microbiology ; Enterocolitis, Pseudomembranous/*epidemiology ; Enterotoxins/analysis ; Feces/*microbiology ; Female ; Humans ; Liver Transplantation/*adverse effects ; Male ; Middle Aged ; Postoperative Complications/*microbiology ; Postoperative Period ; Retrospective Studies ; }, abstract = {OBJECTIVE: We examined the frequency of detection of Clostridium difficile (CD) toxins compared with the recovery of C. difficile in stool specimen cultures among orthotopic liver transplant (OLT) patients with nosocomial diarrhea in the early period.<br><br>MATERIALS AND METHODS: The study included stool samples obtained during the first 30 days after OLT in adults who were suspected of CD-associated diseases. The identification of cultured CD strains was performed by standard microbiological methods. The presence of CD toxins was assayed using a commercial immunoassay.<br><br>RESULTS: All patients were followed prospectively for CD infections from the date of OLT for the first 4 weeks after surgery. Among 54 samples, 16.7% were culture-positive for CD. CD toxins were tested on 54 samples, yielding 63% toxin-positive samples and 30% toxin- and culture-negative results. In the first week after OLT, samples from 19 patients were subjected to CD investigation. Among 19 samples positive for toxin, 52.6% of all samples were culture-negative. We analyzed 35 samples from the second to the fourth week after OLT in 31 recipients. Among 35 samples, 68.6% and 25.7% were positive for CD toxin and for culture, while 20% of samples were negative for toxin and culture.<br><br>CONCLUSION: In our study, 63% of samples were toxin-positive with 16.7% yielding growth of CD and 30% being negative for toxins and cultures.}, }
@article {pmid18000690, year = {2008}, author = {Sapkas, GS and Mavrogenis, AF and Papagelopoulos, PJ}, title = {Transverse sacral fractures with anterior displacement.}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {17}, number = {3}, pages = {342-347}, pmid = {18000690}, issn = {1432-0932}, mesh = {Accidental Falls ; Adolescent ; Adult ; Bone Transplantation ; Decompression, Surgical/instrumentation/methods ; Fecal Incontinence/etiology/physiopathology/surgery ; Female ; Humans ; Internal Fixators/standards ; Laminectomy/instrumentation/methods ; Male ; Paraparesis/etiology/physiopathology/surgery ; Polyradiculopathy/*etiology/physiopathology/*surgery ; Sacrum/*injuries/pathology/*surgery ; Sensation Disorders/etiology/physiopathology/surgery ; Spinal Canal/injuries/pathology/surgery ; Spinal Cord Compression/etiology/physiopathology/surgery ; Spinal Fractures/*complications/physiopathology/*surgery ; Spinal Fusion/instrumentation/methods ; Spinal Nerve Roots/injuries/pathology/surgery ; Suicide, Attempted ; Treatment Outcome ; Urinary Incontinence/etiology/physiopathology/surgery ; }, abstract = {Transverse fractures of the sacrum with anterior displacement are the rarest type of transverse sacral fractures. They usually occur at the S1-S2 region in suicide jumpers. A clinical study was performed to evaluate the diagnosis, treatment and outcome of transverse sacral fractures with anterior displacement. We present six patients with a transverse fracture of the sacrum with anterior displacement. All patients presented with bowel and bladder dysfunction, perineal anesthesia, sensory and motor deficits at the lower extremities. Prompt diagnosis of the sacral fracture was obtained in five of the six patients. Operative treatment including lumbosacral laminectomies, spine instrumentation and fusion was done in all patients. Neurological recovery was almost complete in one patient, incomplete in four patients, and none in one patient. Although reduction of the fracture was not ideal in many of these patients, long-term clinical and radiographic follow-up, and neurological improvement were rewarding.}, }
@article {pmid17990393, year = {2007}, author = {Zmora, O and Tulchinsky, H and Ron, Y}, title = {[New horizons in the treatment of fecal incontinence].}, journal = {Harefuah}, volume = {146}, number = {10}, pages = {776-80, 813}, pmid = {17990393}, issn = {0017-7768}, mesh = {Fecal Incontinence/psychology/radiotherapy/*therapy ; Humans ; Quality of Life ; Radiofrequency Therapy ; }, abstract = {Fecal incontinence affects the quality of life, and causes significant embarrassment. Incontinence mostly affects elderly females. The majority of affected individuals do not seek medical attention because of embarrassment and unawareness of treatment options. Assessment of the severity of incontinence and its effect on the quality of life and evaluation of the anatomy and function of the pelvic floor, rectum and anus, are essential for the proper selection of treatment options. In mild to moderate incontinence, non-invasive treatment with diet and biofeedback may be worthwhile. Invasive treatments include minor procedures, such as "bulking" of the internal sphincter, using injectable agents or radiofrequency energy, and major surgical procedures such as neosphincter operations using the gracilis muscle or artificial bowel sphincter. This review focuses on the new treatment modalities of fecal incontinence.}, }
@article {pmid17970549, year = {2007}, author = {Leyva-Martínez, S and Fernández-Lloret, S and Martín-Ruiz, JL}, title = {[Massive intestinal resection. Nutritional adaptation process].}, journal = {Nutricion hospitalaria}, volume = {22}, number = {5}, pages = {616-620}, pmid = {17970549}, issn = {0212-1611}, mesh = {Abdominal Injuries/rehabilitation/*surgery ; Adult ; Anastomosis, Surgical ; Cholecystectomy ; Colon/*surgery ; Combined Modality Therapy ; Diuresis ; Enteral Nutrition ; Fluid Therapy ; Food, Formulated ; Humans ; Jejunostomy ; Jejunum/*surgery ; Male ; Mesenteric Artery, Superior/*injuries ; Nutritional Support/*methods ; Parenteral Nutrition ; Short Bowel Syndrome/blood/etiology/rehabilitation/*therapy ; Splenectomy ; }, abstract = {INTRODUCTION: Massive small bowel resection (MSBR) with a remnant jejunum shorter than 60 cm produces severe water, electrolytes, vitamins and protein-caloric depletion. While waiting for a viable intestinal transplantation, most of MSBR patients depend on total parenteral nutrition (TPN).<br><br>CLINICAL CASE: 32 years old male, with MSBR due to sectioning trauma of the superior mesenteric artery root. First surgical intervention: jejunostomy with small bowel, right colon, and spleen resection. Six months later: jejunocolic anastomosis with 12-cm long jejunum remnant and prophylactic cholecystectomy.<br><br>NUTRITIONAL INTERVENTION: 1st phase. Hemodynamic stabilization and enteral stimulation (6 months): TPN + enteral nutrition with elemental formula + oral glucohydroelectrolitic solution (OGHS) + 15 g/d of oral glutamine + omeprazol. Clinical course indicators: biochemistry, I/L balance. 2a phase. Digestive adaptation with colonic integration (8 months): replacement of TPN by part-time peripheral PN. Progressive cooked diet complemented with pancreatic poly-enzyme preparation, omeprazol, OGHS, glutamine, elemental formula. Clinical course indicators: biochemistry, diuresis, weight and feces. 3a phase. Auto-sufficiency without parenteral dependence: fragmented free oral diet supplemented with pancreatic poly-enzyme preparation, mineralized beverages, enteral formula supplement, Ca and Mg oral supplements, oral multivitamin and mineral preparation, monthly IM vitamin B12. Current situation actual (52 months): slight ponderal gain, diuresis > liter/day, 2-3 normal feces, no clinical signs of any deficiency and normal blood levels of micronutrients.<br><br>CONCLUSION: It may be possible to withdraw from PN in MSBR considering, as in this case, favorable age and etiology and early implementation of an appropriate protocol of remnant adaptation.}, }
@article {pmid17963518, year = {2007}, author = {Rezaï, K and Lokiec, F and Grandjean, I and Weill, S and de Cremoux, P and Bordier, V and Ekue, R and Garcia, M and Poupon, MF and Decaudin, D}, title = {Impact of imatinib on the pharmacokinetics and in vivo efficacy of etoposide and/or ifosfamide.}, journal = {BMC pharmacology}, volume = {7}, number = {}, pages = {13}, pmid = {17963518}, issn = {1471-2210}, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Antineoplastic Agents, Phytogenic/metabolism/*pharmacokinetics/therapeutic use ; Benzamides ; Carcinoma, Non-Small-Cell Lung/drug therapy/*metabolism ; Chromatography, High Pressure Liquid ; Drug Synergism ; Etoposide/metabolism/*pharmacokinetics/therapeutic use ; Female ; Humans ; Ifosfamide/metabolism/*pharmacokinetics/therapeutic use ; Imatinib Mesylate ; Lung Neoplasms/drug therapy/*metabolism ; Mice ; Mice, Nude ; Piperazines/*pharmacology ; Pyrimidines/*pharmacology ; Transplantation, Heterologous ; }, abstract = {BACKGROUND: Using a human small cell lung cancer (SCLC) xenografted in nude mice, we have previously reported enhanced tumor growth inhibition following chemotherapy in combination with imatinib (STI571). We therefore investigated the in vivo impact of imatinib on the pharmacokinetics and efficacy of chemotherapy.<br><br>METHODS: Two different human tumors were used: SCLC6 small cell lung cancer xenografted in nude mice, and LY-3 EBV-associated human B-cell lymphoma xenografted in SCID mice. Plasma, urine, and fecal concentrations of etoposide (VP16) were determined by a validated high performance liquid chromatography method. Plasma concentrations of ifosfamidewere determined by a validated gas chromatography assay with nitrogen-phosphorus detection.<br><br>RESULTS: Slight tumor growth inhibition was induced by imatinib administered alone in one in vivo EBV-associated B-cell lymphomatous xenograft. In contrast, an increase of the chemotherapy-induced antitumor effect was observed in the lymphoma model but not in a small cell lung cancer model when mice bearing human xenografted tumors were treated concomitantly by imatinib and chemotherapy. This antitumor effect was not influenced by concomitant administration of fluconazole. The AUC0-3 h (Area Under the concentration-time Curve) of etoposide was increased when mice were treated with etoposide + imatinib due to decreased fecal excretion. In contrast, imatinib did not appear to influence the urinary excretion of etoposide, and concomitant administration of the CYP3A4 inhibitor, fluconazole, with imatinib did not modify the pharmacokinetics of etoposide plus imatinib alone.<br><br>CONCLUSION: Altogether, these results therefore justify further prospective phase I and II clinical trials with combinations of etoposide-based chemotherapy and imatinib in patients with certain cancers, such as malignant lymphoma, with careful toxicologic monitoring.}, }
@article {pmid17926813, year = {2007}, author = {Sanad, MM and Al-Malki, JS}, title = {Cryptosporidiosis among immunocompromised patients in Saudi Arabia.}, journal = {Journal of the Egyptian Society of Parasitology}, volume = {37}, number = {2 Suppl}, pages = {765-774}, pmid = {17926813}, issn = {1110-0583}, mesh = {Adolescent ; Adult ; Age Factors ; Animals ; Child ; Child, Preschool ; Cryptosporidiosis/*epidemiology ; Cryptosporidium parvum/immunology/*isolation &amp; purification ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay/methods ; Feces/parasitology ; Female ; Humans ; *Immunocompromised Host ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Prevalence ; Saudi Arabia/epidemiology ; Sensitivity and Specificity ; Sex Factors ; }, abstract = {A total of (408) immunocompromised Saudi patients (<2 - >60 years) checked for Cryptosporidium infection showed 69.7% and 64.2% infection rates by Kinyoun's acid fast staining for oocysts and a monoclonal ELISA kit for C. parvum coproantigen detection respectively (P > 0.05). Microscopic examination of stained faecal smears was more sensitive than ELISA (P > 0.05) &amp; showed 84.4% sensitivity, 81.7% specificity &amp; 83.8% diagnostic accuracy. Infection rates of 47.6%, 78.2% &amp; 82.3% were obtained by microscopic examination for children with chronic diarrhea and malnutrition, patients receiving immunosuppressive (I.S.) drugs for organ transplantation or cancers and patients with HIV and chronic diarrhoea respectively. Infection rates of 84% &amp; 74.3% were in patients receiving I.S. drugs for organ transplantation and malignancy respectively. In all patients, the highest infection rate (84%) was among age group 16-40 years while the least (35.3%) was among infants <2 years (P<0.001). Infections in males (73.9%) was significantly (P < 0.05) higher than females (62.6%). This high prevalence rate revealed the first reported for cryptosporidiosis among immunocompromised Saudis, indicating the presence of infection source(s) (nosocomial), and thus, transmission in Saudi Arabia.}, }
@article {pmid17926002, year = {2007}, author = {Terletskaia-Ladwig, E and Leinmüller, M and Schneider, F and Meier, S and Enders, M}, title = {Laboratory approaches to the diagnosis of adenovirus infection depending on clinical manifestations.}, journal = {Infection}, volume = {35}, number = {6}, pages = {438-443}, doi = {10.1007/s15010-007-6340-4}, pmid = {17926002}, issn = {0300-8126}, mesh = {Adenoids/virology ; Adenovirus Infections, Human/*diagnosis ; Adenoviruses, Human/genetics/*isolation &amp; purification ; Bone Marrow Transplantation/adverse effects ; Cell Line ; Child ; Child, Preschool ; Conjunctiva/virology ; DNA, Viral/genetics ; Enzyme-Linked Immunosorbent Assay/*methods ; Feces/virology ; Gastroenteritis/diagnosis/virology ; Humans ; Pharynx/virology ; Polymerase Chain Reaction/methods ; Respiratory Tract Infections/virology ; Retrospective Studies ; Sensitivity and Specificity ; Viral Plaque Assay ; }, abstract = {BACKGROUND: While commercial enzyme immunoassays (EIA) intended for the detection of adenovirus in fecal specimens are widely used, there are no rapid, convenient, and sensitive commercial tests available for the detection of adenoviruses in respiratory and conjunctival specimens. The applicability of EIA for the detection of adenovirus in stool and throat samples was investigated. One-day rapid culture assay (RCA) for the detection of adenovirus in respiratory and conjunctival specimens was developed and evaluated.<br><br>PATIENTS AND METHODS: Stool samples from patients with gastroenteritis were tested by adenovirus EIA and by cell culture using human embryonic lung cells (HEL) and Graham 293 cells. Blood and stool samples from two BMT patients were also tested for adenovirus by PCR for at least 6 months. Throat specimens from patients with respiratory infections and conjunctival specimens were used for the evaluation of 1-day RCA compared with conventional adenovirus isolation in Graham 293 cells.<br><br>RESULTS: A total of 3,860 stool samples were tested by EIA Ridascreen, 8,169 by Novitec, and 2,218 by ProSpectT yielding 135 (3.5%), 308 (3.7%), and 77 (3.5%) positive results, respectively. From 305 Ridascreen- and 340 Novitec-negative stool samples, adenoviruses were isolated in three (0.9%) and eight (2.4%) cases, respectively, including two patients undergoing BMT. Multiple sequential stool samples from one BMT patient were repeatedly negative by EIA, but positive by PCR and cell culture. Graham 293 cells were better suited for isolation of adenovirus than HEL. EIA proved unreliable for detecting adenovirus in throat swabs. The sensitivity and specificity of RCA in throat swabs were 90% (37/41) and 100% (64/64), respectively, and 76% (16/21) and 100% (132/132) in conjunctival specimens, respectively.<br><br>CONCLUSIONS: Generally, EIA is sufficiently sensitive for the diagnosis of adenovirus-associated diarrhea. However, it may not be sensitive enough to detect adenovirus in immunocompromised patients undergoing BMT and shedding very few viral particles in stools. Thus, in such cases, a more sensitive assay, such as PCR, is recommended. Furthermore, EIA is not sufficiently sensitive for the reliable detection of adenoviruses in throat swabs. One-day RCA may be useful for the detection of adenoviruses in respiratory and conjunctival specimens.}, }
@article {pmid17899300, year = {2008}, author = {Li Destri, G and Scilletta, B and Tomaselli, TG and Zarbo, G}, title = {Rectovaginal fistula: a new approach by stapled transanal rectal resection.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {12}, number = {3}, pages = {601-603}, pmid = {17899300}, issn = {1091-255X}, mesh = {Adult ; Delivery, Obstetric/adverse effects ; Digestive System Surgical Procedures/*methods ; Female ; Humans ; Rectovaginal Fistula/etiology/*surgery ; *Surgical Stapling ; Suture Techniques ; }, abstract = {Many surgical procedures have been developed to repair rectovaginal fistulas even if no "procedure of choice" is reported. The authors report a case of relatively uncommon, complex, medium-high post-obstetric rectovaginal fistula without sphincteral lesions and treated with a novel tailored technique. Our innovative surgical management consisted of preparing the neck of the fistula inside the vagina and folding it into the rectum so as to enclose the fistula within two semicontinuous sutures (stapled transanal rectal resection); no fecal diversion was performed. Postoperative follow-up at 9 months showed no recurrence of the fistula.}, }
@article {pmid17895849, year = {2007}, author = {Reszetow, J and Hać, S and Dobrowolski, S and Stefaniak, T and Wajda, Z and Gruca, Z and Sledziński, Z and Studniarek, M}, title = {Biliary versus alcohol-related infected pancreatic necrosis: similarities and differences in the follow-up.}, journal = {Pancreas}, volume = {35}, number = {3}, pages = {267-272}, doi = {10.1097/MPA.0b013e31805b8319}, pmid = {17895849}, issn = {1536-4828}, mesh = {Acute Disease ; Adult ; Aged ; Biliary Tract Diseases/complications/surgery ; Blood Glucose/analysis ; Calcinosis/epidemiology/etiology ; Exocrine Pancreatic Insufficiency/epidemiology/etiology ; Feces/enzymology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Necrosis ; Pancreas/diagnostic imaging/physiopathology ; Pancreatectomy/methods/statistics &amp; numerical data ; Pancreatic Elastase/analysis ; Pancreatitis, Acute Necrotizing/*complications/diagnostic imaging/surgery ; Pancreatitis, Alcoholic/*complications/diagnostic imaging/surgery ; Quality of Life ; Radiography ; Severity of Illness Index ; Sphincterotomy, Endoscopic/statistics &amp; numerical data ; Survivors/psychology/statistics &amp; numerical data ; }, abstract = {OBJECTIVES: Infected pancreatic necrosis (IPN) is a serious complication of acute pancreatitis. Data concerning survivors' quality of life and pancreatic functions are scarce. Follow-up of the patients with alcohol and biliary etiology of IPN treated with open necrosectomy was performed.<br><br>METHODS: Twenty-eight survivors after operative treatment (Bradley procedure) of IPN were followed up 24 to 96 months after discharge from the hospital (10 biliary and 18 alcohol patients). Their exocrine and endocrine pancreatic functions and quality of life (Functional Assessment of Chronic Illness Therapy scale) were evaluated. Pancreatic tissue remaining after necrosectomy was visualized by use of contrast-enhanced computed tomography (CT).<br><br>RESULTS: In 44.4% of alcohol-induced IPN patients, the presence of the whole pancreas was shown on the follow-up CT, contrary to the biliary group, where the partial lack of the pancreas was observed in all cases. Pancreatic tissue calcifications were present on CT in 8 patients of alcohol-induced acute pancreatitis group only. Median stool elastase 1 concentrations were 318.1 U/mL in the biliary group and 238.3 U/mL in the alcohol-induced group (not significant). The Functional Assessment of Chronic Illness Therapy scale showed significantly higher social/family and emotional well-being in patients with biliary acute necrotizing pancreatitis.<br><br>CONCLUSIONS: Patients after alcohol-induced IPN had lower quality of life compared with biliary etiology. Biliary and alcohol-induced IPN patients after surgical treatment have nonsignificant differences of endocrine and exocrine pancreatic functions.}, }
@article {pmid17879031, year = {2007}, author = {Dobrowolski, S and Wojciechowski, J and Dobosz, M and Hać, S and Sledziński, Z}, title = {Prospective evaluation of the defecatory functional results in patients following aorto-aortic reconstruction surgery for an abdominal aortic aneurysm.}, journal = {Surgery today}, volume = {37}, number = {10}, pages = {831-836}, pmid = {17879031}, issn = {0941-1291}, mesh = {Aged ; Aorta/physiopathology/*surgery ; Aortic Aneurysm, Abdominal/physiopathology/*surgery ; *Defecation ; Female ; Health Status Indicators ; Humans ; Hypogastric Plexus/*injuries ; Male ; Middle Aged ; *Postoperative Complications ; Prospective Studies ; *Plastic Surgery Procedures ; Rectum/innervation ; Risk Factors ; Surveys and Questionnaires ; Time Factors ; Trauma, Nervous System/etiology ; }, abstract = {PURPOSE: Anterior rectal resections have been associated with postoperative bowel function abnormalities, a condition defined as anterior resection syndrome. Autonomic denervation could be one of the possible mechanisms underlying this complication. Damage to the preaortic tissue containing autonomic nervous plexus during abdominal aortic reconstruction surgery may affect the anorectal defecation function.<br><br>METHODS: The anorectal function was prospectively studied in 22 patients undergoing abdominal aortic reconstruction surgery. The patients were examined preoperatively and 6 months postoperatively by symptom-specific questionnaires.<br><br>RESULTS: Postoperatively, the patients showed no significant impairment of the anorectal functions in both constipation- and fecal incontinence-specific questionnaires. Self-estimation of the defecatory function was slightly lower compared with preoperative scores.<br><br>CONCLUSION: An injury to the intermesenteric, inferior mesenteric, and superior hypogastric plexuses does not significantly influence the defecatory functions in patients following abdominal reconstruction surgery for an abdominal aortic aneurysm.}, }
@article {pmid17828141, year = {2007}, author = {Shelygin, IuA and Poletov, NN and Nekhrikova, SV and Fomenko, OIu and Podmarenkov, VA}, title = {[Results of graciloplasty at the patients with complete insufficiency of anal sphincter].}, journal = {Khirurgiia}, volume = {}, number = {7}, pages = {45-50}, pmid = {17828141}, issn = {0023-1207}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/physiopathology/*surgery ; Electric Stimulation Therapy ; Electromyography ; Fecal Incontinence/physiopathology/rehabilitation/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Preoperative Care ; Time Factors ; Treatment Outcome ; }, abstract = {Graciloplasty was performed at 43 patients with III stage of anal sphincter insufficiency. Program of preoperative preparation including therapeutic physical training and electrostimulation of gracilis muscle permitted to improve muscle's functional activity on 19.1%. Functional postoperative rehabilitation permitted to prevent the degenerative processes on displaced muscle and to improve the function of fecal continence. The good results after graciloplasty with functional rehabilitation has been achieved at 80%, satisfactory results at 8.6% patients.}, }
@article {pmid17824984, year = {2007}, author = {Songne, K and Scotté, M and Lubrano, J and Huet, E and Lefébure, B and Surlemont, Y and Leroy, S and Michot, F and Ténière, P}, title = {Treatment of anovaginal or rectovaginal fistulas with modified Martius graft.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {9}, number = {7}, pages = {653-656}, doi = {10.1111/j.1463-1318.2007.01232.x}, pmid = {17824984}, issn = {1462-8910}, mesh = {Adolescent ; Adult ; Crohn Disease/surgery/therapy ; Fecal Incontinence/therapy ; Female ; General Surgery/*methods ; Humans ; Middle Aged ; Models, Anatomic ; Rectovaginal Fistula/surgery/*therapy ; Retrospective Studies ; Time Factors ; *Transplants ; Vaginal Fistula/surgery/*therapy ; }, abstract = {OBJECTIVE: The treatment of ano- or rectovaginal fistula is still difficult. The use of the Martius flap is well described as an adjunctive technique in their repair. We report our experience of a modified Martius flap in the management of ano- or rectovaginal fistula.<br><br>METHOD: This is a retrospective study of 14 women presenting with an anovaginal (n = 9) or rectovaginal fistula (n = 5). All were treated by a modified Martius graft. The aetiology included Crohn's disease (n = 7), ulcerative colitis (n = 4), radio-induced (n = 1), obstetric (n = 1) and villous tumour (n = 1).<br><br>RESULTS: All 14 fistulas healed within the 3 months after surgery. Subsequently, two patients with Crohn's disease required an abdominoperineal resection owing to progressive anal lesions. Two other patients experienced faecal incontinence which improved with functional rehabilitation treatment.<br><br>CONCLUSION: A modified Martius flap is a valuable option in the treatment of ano- or rectovaginal fistula. In the case of Crohn's disease, however, the prognosis depends primarily on subsequent clinical evolution of the condition.}, }
@article {pmid17676262, year = {2007}, author = {Altomare, DF and Rinaldi, M and Bucaria, V and Marino, F and Lobascio, P and Sallustio, PL}, title = {Overlapping sphincteroplasty and modified lotus petal flap for delayed repair of traumatic cloaca.}, journal = {Techniques in coloproctology}, volume = {11}, number = {3}, pages = {268-270}, pmid = {17676262}, issn = {1123-6337}, mesh = {Cloaca/*injuries/*surgery ; Female ; Humans ; Manometry ; Middle Aged ; Obstetric Labor Complications/*surgery ; Pregnancy ; *Surgical Flaps ; Urinary Incontinence/etiology/surgery ; }, abstract = {Traumatic cloaca is a disabling condition characterized by disruption of the perineal body, anterior sphincter tears and loss of the distal rectovaginal septum. Anterior overlapping sphincteroplasty is the method of choice to treat faecal incontinence caused by obstetric injury. However, reconstruction of large perineal body defects may be a challenging task for surgeons. Herein we describe the successful use of a modified lotus petal flap following overlapping sphincteroplasty to repair a traumatic cloaca that had occurred during vaginal delivery 20 years earlier. After 3 months of follow-up and ileostomy closure, the patient had a good aesthetic result and only minor faecal incontinence episodes not requiring pads, fully recovered urinary continence and a significant improvement in her quality of life.}, }
@article {pmid17667511, year = {2007}, author = {Sudan, D and Vargas, L and Sun, Y and Bok, L and Dijkstra, G and Langnas, A}, title = {Calprotectin: a novel noninvasive marker for intestinal allograft monitoring.}, journal = {Annals of surgery}, volume = {246}, number = {2}, pages = {311-315}, pmid = {17667511}, issn = {0003-4932}, mesh = {Adolescent ; Adult ; Biomarkers/metabolism ; Biopsy ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Feces/chemistry ; Follow-Up Studies ; Graft Rejection/*metabolism/pathology ; Humans ; Infant ; Intestine, Small/metabolism/pathology/*transplantation ; Leukocyte L1 Antigen Complex/*metabolism ; Middle Aged ; Pilot Projects ; Predictive Value of Tests ; ROC Curve ; Retrospective Studies ; Transplantation, Homologous ; }, abstract = {OBJECTIVE: To identify a noninvasive screening test for intestinal allograft monitoring.<br><br>SUMMARY BACKGROUND DATA: Intestinal allograft rejection is difficult to distinguish from other causes of diarrhea and can rapidly lead to severe exfoliation or death. Protocol biopsies are standard for allograft monitoring but may cause serious complications. No noninvasive test has shown clinical utility for monitoring of the intestinal allograft.<br><br>METHODS: Calprotectin levels (n = 68) were measured in this pilot study from ileostomy effluent in patients with histologic evidence of acute rejection (n = 12), viral enteritis (n = 5), and nonspecific inflammation (n = 16) and compared with those with normal allograft histology (n = 35).<br><br>RESULTS: Median stool calprotectin levels from patients with rejection were significantly higher than those from patients with viral enteritis or normal biopsies [198 mg/kg compared with 7 and 19 mg/kg, respectively (P = 0.0002)]. Receiver operator characteristics suggest the optimal cut-off level to distinguish rejection from other diagnoses is 92 mg/kg with specificity of 77% and sensitivity of 83%. Although false-positive results occurred in 26% of patients with normal biopsies and 30% with nonspecific changes, no treated episode of acute rejection was below the cutoff. In addition, in 2 patients with serial levels, elevations in the calprotectin levels preceded histologic changes by 6 to 18 days.<br><br>CONCLUSIONS: Low stool calprotectin levels correlate well with a low risk for intestinal allograft rejection. If confirmed, biopsies may be reserved in the future for confirmation of rejection, eliminating protocol biopsies, and immunosuppressive changes could potentially be made before allograft injury.}, }
@article {pmid17639423, year = {2008}, author = {Oberwalder, M and Zitt, M and Wöntner, C and Fiegl, H and Goebel, G and Zitt, M and Köhle, O and Mühlmann, G and Ofner, D and Margreiter, R and Müller, HM}, title = {SFRP2 methylation in fecal DNA--a marker for colorectal polyps.}, journal = {International journal of colorectal disease}, volume = {23}, number = {1}, pages = {15-19}, pmid = {17639423}, issn = {0179-1958}, mesh = {Adenomatous Polyps/*genetics/pathology ; Adult ; Aged ; Biomarkers, Tumor/*genetics ; Case-Control Studies ; Colonic Polyps/*genetics/pathology ; Colonoscopy ; Colorectal Neoplasms/*genetics/pathology ; DNA/analysis ; *DNA Methylation ; Feces/chemistry ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Hyperplasia ; Male ; Membrane Proteins/*genetics ; Middle Aged ; Precancerous Conditions/*genetics/pathology ; Young Adult ; }, abstract = {INTRODUCTION: DNA methylation of secreted frizzled-related proteins (SFRPs) can be detected in colorectal cancer (CRC) tissue, in tissue of adenomas, and in aberrant crypt foci, whereas in normal colorectal mucosa tissue, SFRP genes are unmethylated. Recently, our study group was able to demonstrate SFRP2 methylation as the most sensitive single DNA-based marker in stool for identification of CRC. The purpose of this study was to clarify whether SFRP2 methylation in fecal DNA can be found in stool of individuals with hyperplastic and adenomatous colorectal polyps.<br><br>MATERIALS AND METHODS: Patients who were diagnosed with colorectal polyps or showed negative colonoscopy were included in this study. DNA from stool samples was isolated. SFRP2 methylation was assessed by means of MethyLight.<br><br>RESULTS: Stool samples from 68 individuals were checked for DNA content; 23% of the samples (6 of 26) from healthy controls, 46% of the samples (6 of 13) from patients with hyperplastic polyps, and 45% of the samples (13 of 29) from patients with adenomas were positive for human DNA. SFRP2 methylation in stool samples was found in none of the healthy controls, in 33% (2 of 6) patients with hyperplastic polyps, and in 46% (6 of 13) patients with adenomas. Statistical analysis revealed that the frequency of SFRP2 methylation increased significantly (P=0.028) from healthy controls to patients with hyperplastic polyps and to patients with adenomas.<br><br>CONCLUSIONS: In the current study, we report for the first time that SFRP2 methylation in fecal DNA increases significantly from healthy controls to patients with hyperplastic polyps and to patients with adenomas. SFRP2 methylation may serve as a marker for molecular stool-based adenoma and CRC screening.}, }
@article {pmid17615029, year = {2007}, author = {Santacroce, L and Bottalico, L and Mangini, F}, title = {Dental hygiene procedure in a patient with Giardia lamblia infection.}, journal = {International journal of dental hygiene}, volume = {5}, number = {3}, pages = {187-189}, doi = {10.1111/j.1601-5037.2007.00240.x}, pmid = {17615029}, issn = {1601-5037}, mesh = {Adult ; *Dental Care for Chronically Ill ; *Dental Prophylaxis ; Giardiasis/*complications ; Heart Failure/*complications ; *Heart Transplantation ; Humans ; Male ; }, abstract = {INTRODUCTION: Giardiasis, or Giardia lamblia infection, is the most common parasitosis of the human digestive tract. It is highly contagious and mostly occurs in warm climates. Children are especially susceptible to infection. MICROBIOLOGICAL FEATURES: The infection can sporadically occur anywhere and waterborne outbreaks have been reported in some countries. Hence, the prevention of giardiasis depends on proper sanitation. Once ingested through contaminated water, Giardia cysts adhere to the intestinal surface. The parasite feeds on the mucous secretions of the intestine and may produce severe infections which can interfere with nutrient absorption. Symptoms in affected individuals usually include diarrhoea, dehydration, stomach cramps, gas, and weight loss.<br><br>DIAGNOSIS: Diagnosis is based on the detection of cysts in fecal samples. Treatment includes the use of metronidazole and other drugs that are effective in clearing the infection within a few days.<br><br>CASE REPORT: We report the recent case of a patient with Giardiasis who received dental hygiene procedures and discuss the interventions required in consideration of the patient's concomitant heart condition.}, }
@article {pmid17605739, year = {2007}, author = {Stelzmueller, I and Wiesmayr, S and Swenson, BR and Biebl, M and Goegele, H and Margreiter, R and Bonatti, H}, title = {Rotavirus enteritis in solid organ transplant recipients: an underestimated problem?.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {9}, number = {4}, pages = {281-285}, doi = {10.1111/j.1399-3062.2007.00251.x}, pmid = {17605739}, issn = {1398-2273}, mesh = {Adult ; Aged ; Austria ; Child ; Child, Preschool ; Diarrhea/*epidemiology/therapy/virology ; Feces/virology ; Female ; Hospitalization/statistics &amp; numerical data ; Hospitals, University ; Humans ; Liver Transplantation/adverse effects ; Male ; Middle Aged ; Organ Transplantation/*adverse effects ; Prevalence ; *Rotavirus ; Rotavirus Infections/*epidemiology/therapy/virology ; }, abstract = {BACKGROUND: Diarrhea in solid organ transplantation can be a complication with a high morbidity and mortality. Rotavirus (RV) infection normally occurs in children up to 3 years of age and often presents with severe diarrhea; however, it can also affect adults. We investigated the prevalence and outcome of RV infections in both adult and pediatric patients after solid organ transplantation.<br><br>PATIENTS AND METHODS: Retrospective analysis of RV-related enteritis in solid organ transplant recipients with a minimum of a 1-year follow-up from a single center between 2000 and 2004.<br><br>RESULTS: Within our cohort of 1303 solid organ transplants, RV infection was observed in 19 patients (1.5%); 14 of these were liver recipients. Infection was most prevalent among pediatric liver recipients, with 52% (11/21) of the children affected. Five adults acquired the infection during their initial hospitalization. Two adult patients had to be readmitted following late-onset RV infection. In all cases, infection was self-limiting, but led to prolonged hospitalization because of significant loss of fluids and electrolytes.<br><br>CONCLUSIONS: RV enteritis is a common infection in pediatric solid organ recipients but may also affect adult patients.}, }
@article {pmid17594646, year = {2007}, author = {Koru, O and Araz, RE and Yilmaz, YA and Ergüven, S and Yenicesu, M and Pektaş, B and Tanyüksel, M}, title = {Case report: Isospora belli infection in a renal transplant recipent.}, journal = {Turkiye parazitolojii dergisi}, volume = {31}, number = {2}, pages = {98-100}, pmid = {17594646}, issn = {1300-6320}, mesh = {Adult ; Animals ; Diarrhea/*parasitology ; Humans ; *Immunocompromised Host ; Isospora/*isolation &amp; purification ; Isosporiasis/*etiology/immunology ; *Kidney Transplantation ; Male ; }, abstract = {Isospora belli, an opportunistic protozoon, is one of the most commonly recognized causes of diarrhea in patients with acquired immunodeficiency syndrome (AIDS). Infection is acquired through fecal contaminated food or water, and generally diagnosed by examination of stool and/or duodenum biopsy specimens with acid-fast staining. Here, we present an uncommon case, chronic diarrhea caused by I. belli infection in a patient who is a renal transplant recipient.}, }
@article {pmid17520710, year = {2007}, author = {Ganio, E and Altomare, DF and Milito, G and Gabrielli, F and Canuti, S}, title = {Long-term outcome of a multicentre randomized clinical trial of stapled haemorrhoidopexy versus Milligan-Morgan haemorrhoidectomy.}, journal = {The British journal of surgery}, volume = {94}, number = {8}, pages = {1033-1037}, doi = {10.1002/bjs.5677}, pmid = {17520710}, issn = {0007-1323}, mesh = {Adult ; Aged ; Aged, 80 and over ; Defecation/physiology ; Fecal Incontinence/*etiology ; Female ; Hemorrhoids/physiopathology/*surgery ; Humans ; Male ; Manometry ; Middle Aged ; Patient Satisfaction ; Postoperative Complications/*etiology ; Recurrence ; *Surgical Stapling ; Treatment Outcome ; }, abstract = {INTRODUCTION: Stapled haemorrhoidopexy is less painful than Milligan-Morgan haemorrhoidectomy, allowing an earlier return to working activities, but its long-term efficacy is not fully established. This study reports the long-term follow-up of a randomized clinical trial comparing the two techniques in 100 patients affected by third- and fourth-degree haemorrhoids.<br><br>METHODS: All patients were contacted and invited to attend the clinic to assess long-term functional outcome. The degree of continence and satisfaction were assessed by questionnaire. Anal manometry and anoscopy were performed.<br><br>RESULTS: Eighty patients were available after a median follow-up of 87 months. No statistically significant differences were found between the two groups in terms of incontinence, stenosis, pain, bleeding, residual skin tags or recurrent prolapse. A tendency towards a higher recurrence rate was reported in patients with fourth-degree haemorrhoids, irrespective of the technique used. No significant changes in anal manometric values were found after surgery in either group.<br><br>CONCLUSION: Both techniques are effective in the long term.}, }
@article {pmid17511822, year = {2007}, author = {Kamboj, M and Mihu, CN and Sepkowitz, K and Kernan, NA and Papanicolaou, GA}, title = {Work-up for infectious diarrhea after allogeneic hematopoietic stem cell transplantation: single specimen testing results in cost savings without compromising diagnostic yield.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {9}, number = {4}, pages = {265-269}, doi = {10.1111/j.1399-3062.2007.00230.x}, pmid = {17511822}, issn = {1398-2273}, mesh = {Adult ; Child ; Child, Preschool ; Cost-Benefit Analysis ; Diarrhea/*diagnosis/microbiology/parasitology/virology ; *Feces/microbiology/parasitology/virology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Microbiological Techniques/*economics/methods/*standards ; Transplantation, Homologous/*adverse effects ; }, abstract = {BACKGROUND: Diarrhea is a common complication of allogeneic bone marrow transplantation. Microbiologic stool studies are frequently ordered to rule out infectious etiology. The utility of examining multiple stool specimens per diarrheal episode has not been examined.<br><br>METHODS: . We performed a retrospective review of 169 adult and pediatric patients who underwent hematopoietic stem cell transplantation at Memorial Sloan-Kettering Cancer Center from January 1, 2000 though December 31, 2001, who had at least 1 microbiologic stool study. We report on the incidence of enteric pathogens in our population and diagnostic yield of stool studies. A diarrheal episode was defined as a 14-day period from the date of the first stool study. Cost savings analysis was based on projected savings from implementation of proposed guidelines to the study population.<br><br>RESULTS: A total of 1649 stool tests were performed (mean 10.6 tests per patient). An infectious cause of diarrhea was found in 45 (28.8%) patients. Diagnostic yield was 6.2% for Clostridum difficile toxin assay, 12.9% for viral cultures, and 1.3% for rotavirus enzyme immunoassay. Bacterial cultures for enteric pathogens, examination for parasites, and rotavirus antigen assay combined had 0.5% positive yield.<br><br>CONCLUSIONS: Testing of multiple specimens per diarrheal episode did not increase diagnostic yield. The estimated cost savings by implementing single testing for each type of stool study per diarrheal episode was $49,764 annually (in 2001 US dollars). Judicious use of stool tests to evaluate diarrhea results in significant cost savings without compromising diagnostic yield.}, }
@article {pmid17511817, year = {2007}, author = {Arslan, H and Inci, EK and Azap, OK and Karakayali, H and Torgay, A and Haberal, M}, title = {Etiologic agents of diarrhea in solid organ recipients.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {9}, number = {4}, pages = {270-275}, doi = {10.1111/j.1399-3062.2007.00237.x}, pmid = {17511817}, issn = {1398-2273}, mesh = {Adult ; Anti-Bacterial Agents/adverse effects ; Colchicine/adverse effects ; Diarrhea/chemically induced/*etiology/microbiology/parasitology/virology ; Feces/microbiology/parasitology/virology ; Humans ; Immunosuppressive Agents/adverse effects ; Kidney Transplantation/*adverse effects ; Laxatives/adverse effects ; Liver Transplantation/*adverse effects ; Mycophenolic Acid/adverse effects/analogs &amp; derivatives ; }, abstract = {After transplantation, diarrhea may be caused by infectious agents, drug-specific effects, metabolic conditions, or mechanical complications of surgery. Determining the cause helps to determine whether to initiate antimicrobial therapy and the duration of treatment. In this study we aimed to determine the causes of diarrhea in kidney or liver recipients. Fifty-two diarrhea episodes among 43 solid organ recipients were evaluated. The cause of diarrhea was detected in 43 patients (82.6%). Infectious etiologies accounted for 33 out of the 43 episodes (76.7%) in which a specific cause was determined: Giardia lamblia in 9, Cryptosporidium parvum in 7, cytomegalovirus (CMV) in 6, Clostridium difficile in 3, Campylobacter jejuni in 2, Shigella sonnei in 2, Salmonella enteritidis in 1, rotavirus in 1, Entamoeba histolytica in 1, and Blastocystis hominis in 1. Non-infectious etiologies were found for 10 episodes (23.3%): mycophenolate mofetil-associated diarrhea in 5, antibiotic-associated diarrhea in 2, colchicine-associated diarrhea in 2, and laxative drug-associated in 1. Non-infectious etiologies seem to be relatively common causes of diarrhea among transplant recipients. Therapy was adjusted in 5 patients because of mycophenolate mofetil-associated diarrhea. CMV and C. parvum, which are seldom seen in the normal population, were frequent causes of diarrhea in this group. Evaluating the transplant recipients for non-infectious causes of diarrhea is important in prompt diagnosis and treatment.}, }
@article {pmid17448922, year = {2007}, author = {Weinstock, DM and Conlon, M and Iovino, C and Aubrey, T and Gudiol, C and Riedel, E and Young, JW and Kiehn, TE and Zuccotti, G}, title = {Colonization, bloodstream infection, and mortality caused by vancomycin-resistant enterococcus early after allogeneic hematopoietic stem cell transplant.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {13}, number = {5}, pages = {615-621}, doi = {10.1016/j.bbmt.2007.01.078}, pmid = {17448922}, issn = {1083-8791}, mesh = {Adult ; Aged ; Bacteremia/etiology/*microbiology/mortality ; Cross Infection/etiology/*microbiology/mortality ; Enterococcus/classification/*drug effects/pathogenicity ; Feces/microbiology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Male ; Mass Screening/methods ; Middle Aged ; New York/epidemiology ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Analysis ; Transplantation, Homologous/*adverse effects ; Vancomycin Resistance/*drug effects ; }, abstract = {Bloodstream infection caused by vancomycin-resistant enterococcus (VRE) is associated with very high mortality among allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. However, it remains unclear whether VRE bloodstream infection directly causes mortality in the early posttransplant period or is simply a marker of poor outcome. To determine the risk factors for VRE bloodstream infection and its effect on outcome, we followed 92 patients screened for stool colonization by VRE upon admission for alloHSCT. Patient records were reviewed to determine outcomes, including mortality and microbiologic failure. Colonization by VRE was extremely common, occurring in 40.2% of patients. VRE bloodstream infection developed in 34.2% of colonized patients by day +35, compared to 1.8% without VRE colonization (P < .01). VRE bloodstream infection was associated with a significant decrement in survival and frequent microbiologic failure, despite treatment with linezolid and/or daptomycin. Five (35.7%) of 14 patients with VRE bloodstream infection had attributable mortality or contributing mortality from the infection. Strain typing by pulsed-field gel electrophoresis identified 9 different VRE strains among the 37 colonized patients and 5 patients with different strains recovered from the stool and the blood. In conclusion, stool screening effectively identified patients at extremely high risk for VRE bloodstream infection. The high mortality of VRE in the early posttransplant period supports the use of empiric antibiotics with activity against VRE during periods of fever and neutropenia in colonized patients.}, }
@article {pmid17446957, year = {2007}, author = {Kheradpezhouh, M and Taremi, M and Gachkar, L and Aghabozorgi, S and Khoshbaten, M}, title = {Presence and significance of transfusion-transmitted virus infection in Iranian patients on maintenance hemodialysis.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {40}, number = {2}, pages = {106-111}, pmid = {17446957}, issn = {1684-1182}, mesh = {Adult ; Age Factors ; Aged ; Alanine Transaminase/blood ; Antibodies, Viral/blood ; Aspartate Aminotransferases/blood ; Blood Transfusion ; Cross-Sectional Studies ; DNA Virus Infections/*epidemiology/*virology ; DNA, Viral/blood ; Female ; HIV Antibodies/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis C Antibodies/blood ; Hepatitis E virus/immunology ; Humans ; Iran/epidemiology ; Kidney Transplantation ; Male ; Middle Aged ; Polymerase Chain Reaction/methods ; Prevalence ; *Renal Dialysis ; Seroepidemiologic Studies ; Sex Factors ; Torque teno virus/*isolation &amp; purification ; }, abstract = {BACKGROUND AND PURPOSE: Transfusion-transmitted virus (TTV), a recently discovered DNA virus, was first identified in patients with non-A to -G hepatitis following blood transfusion. Transmission is generally via the parenteral route but recent data suggest that TTV can also be transmitted by the fecal-oral route.<br><br>METHODS: This cross-sectional study was conducted in March 2005 and included 324 patients on maintenance hemodialysis (HD) at 3 different centers in Tabriz, Iran. Demographic and clinical data were recorded. Blood samples for virological and biochemical tests were drawn simultaneously. TTV DNA was detected using semi-nested polymerase chain reaction. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase were also measured.<br><br>RESULTS: Overall seroprevalence of TTV was 9.3% (95% confidence interval, 6.1-12.5%). Prevalence rates of hepatitis B surface antigen, hepatitis C virus antibody, and hepatitis E virus antibody were 4.6% (15/324), 20.4% (66/324), and 7.4% (24/324), respectively. Patients were negative for human immunodeficiency virus antibody. There was no association between TTV infection and elevated ALT levels. TTV-positive patients were significantly younger than TTV-negative patients (p=0.018). There was no significant association between TTV positivity and age, gender, duration of HD, positivity for hepatitis B, C, or E virus infection markers, and history of transfusion and transplantation.<br><br>CONCLUSION: We observed low TTV prevalence and no association between TTV and blood-borne infections in our HD patients. TTV infection was not related to elevated levels of liver enzymes; however, the clinical impact of this virus need further investigations.}, }
@article {pmid17446156, year = {2006}, author = {Péron, JM and Mansuy, JM and Izopet, J and Vinel, JP}, title = {[Hepatitis E virus: an emerging disease].}, journal = {Sante (Montrouge, France)}, volume = {16}, number = {4}, pages = {239-243}, pmid = {17446156}, issn = {1157-5999}, mesh = {Adult ; Africa/epidemiology ; Age Factors ; Animals ; Asia/epidemiology ; Child ; Communicable Diseases, Emerging/*epidemiology ; Disease Outbreaks ; Endemic Diseases ; France/epidemiology ; Hepatitis E/*epidemiology/mortality/transmission ; Hepatitis E virus/classification ; Humans ; Immunocompromised Host ; Mexico/epidemiology ; Organ Transplantation ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Factors ; Zoonoses ; }, abstract = {Hepatitis E virus (HEV) is a spherical, non-enveloped, single stranded RNA virus. Four genotypes (1-4) have so far been distinguished. HEV infection can occur either in large epidemics (in endemic regions only: southeast Asia, India, central Asia central, Africa, and Mexico) or in sporadic forms. HEV is transmitted principally by the fecal-oral pathway, that is, hand-to-mouth. There is a risk of transmission from animals to humans. Nearly half of all cases have no or few symptoms. Symptomatic forms can be severe. The mortality rate can reach 20% in pregnant women. Recent reports indicate that autochthonous cases have been contracted in France. Several aspects differentiate sporadic autochthonous hepatitis from that contracted in endemic areas: 1) mean age of onset is older in the former; 2) prognosis is more severe; and 3) prolonged even chronic forms can affect some immunocompromised patients, in particular, those with organ transplants. The diagnosis of hepatitis E must now be considered in any cases of acute hepatitis of unexplained origin in France. Diagnosis relies on RT-PCR testing of blood or stool.}, }
@article {pmid17441968, year = {2008}, author = {Altomare, DF and Spazzafumo, L and Rinaldi, M and Dodi, G and Ghiselli, R and Piloni, V}, title = {Set-up and statistical validation of a new scoring system for obstructed defaecation syndrome.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {10}, number = {1}, pages = {84-88}, doi = {10.1111/j.1463-1318.2007.01262.x}, pmid = {17441968}, issn = {1463-1318}, mesh = {Adult ; Aged ; Case-Control Studies ; Cluster Analysis ; Constipation/*diagnosis/epidemiology/therapy ; Defecography ; Fecal Impaction/*diagnosis/epidemiology/therapy ; Female ; Follow-Up Studies ; Humans ; Incidence ; Intestinal Obstruction/diagnosis/epidemiology/surgery ; Male ; Middle Aged ; Probability ; Reference Values ; Risk Assessment ; *Severity of Illness Index ; Sickness Impact Profile ; Statistics, Nonparametric ; *Surveys and Questionnaires ; Syndrome ; Treatment Outcome ; }, abstract = {OBJECTIVE: There is no objective means to assess the obstructed defaecation syndrome (ODS), to allow evaluation of outcome or to compare the efficacy of treatment including surgery. The study aimed to validate a disease-specific index to quantify severity to allow assessment of the results of treatment in clinical trials, to permit comparison between them.<br><br>METHOD: Seventy-six patients with ODS and 30 healthy controls entered the study after proctologic and ano-rectal physiological investigation. Hirschsprung's disease and slow transit constipation were excluded. An eight-item questionnaire with four or five possible answers was administered by two independent researchers at two different times. The ODS score was the sum of all points with a maximum possible of 31 points. Agreement between the two operators was evaluated by the Kappa coefficient for each single item. The coefficient of repeatability (CR) was assessed by the Bland and Altman plot. The internal consistency was evaluated by the Crohnbach-alpha test. A cluster analysis was carried out on each clinical finding. The Mann-Whitney U-test was used to compare median ODS score between patients and controls.<br><br>RESULTS: The ODS score of the two operators was normally distributed and strongly correlated (r = 0.89). The correlation coefficient between the score assigned to each item by two operators ranged from 0.79 to 0.98. The degree of agreement between the operators was good and the two methods were reproducible (CR = 3.13). There was a significant difference between the mean ODS score for patients and controls (t = 20.70, P < 0.001). The Crohnbach alpha value for internal reliability was +0.513. Cluster analysis showed a different profile between cluster 1 (a nonhomogenous group including rectocoele, intussusception or perineal descent), and cluster 2 (pelvic dysynergia).<br><br>CONCLUSION: The ODS score offers a validated severity of disease index in grading the severity of disease and monitoring the efficacy of therapy.}, }
@article {pmid17436140, year = {2007}, author = {Mueller, MH and Geis, M and Glatzle, J and Kasparek, M and Meile, T and Jehle, EC and Kreis, ME and Zittel, TT}, title = {Risk of fecal diversion in complicated perianal Crohn's disease.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {11}, number = {4}, pages = {529-537}, pmid = {17436140}, issn = {1091-255X}, mesh = {Abscess/complications/surgery ; Adolescent ; Adult ; Anus Diseases/complications/surgery ; Child ; Crohn Disease/complications/*surgery ; *Enterostomy ; Female ; Humans ; Male ; Middle Aged ; Rectovaginal Fistula/complications/surgery ; Risk Factors ; }, abstract = {The purpose of the study was to determine the overall risk of a permanent stoma in patients with complicated perianal Crohn's disease, and to identify risk factors predicting stoma carriage. A total of 102 consecutive patients presented with the first manifestation of complicated perianal Crohn's disease in our outpatient department between 1992 and 1995. Ninety-seven patients (95%) could be followed up at a median of 16 years after first diagnosis of Crohn's disease. Patients were sent a standardized questionnaire and patient charts were reviewed with respect to the recurrence of perianal abscesses or fistulas and surgical treatment, including fecal diversion. Factors predictive of permanent stoma carriage were determined by univariate and multivariate analysis. Thirty of 97 patients (31%) with complicated perianal Crohn's disease eventually required a permanent stoma. The median time from first diagnosis of Crohn's disease to permanent fecal diversion was 8.5 years (range 0-23 years). Temporary fecal diversion became necessary in 51 of 97 patients (53%), but could be successfully removed in 24 of 51 patients (47%). Increased rates of permanent fecal diversion were observed in 54% of patients with complex perianal fistulas and in 54% of patients with rectovaginal fistulas, as well as in patients that had undergone subtotal colon resection (60%), left-sided colon resection (83%), or rectal resection (92%). An increased risk for permanent stoma carriage was identified by multivariate analysis for complex perianal fistulas (odds ratio [OR] 5; 95% confidence interval [CI] 2-18), temporary fecal diversion (OR 8; 95% CI 2-35), fecal incontinence (OR 21, 95% CI 3-165), or rectal resection (OR 30; 95% CI 3-179). Local drainage, setons, and temporary stoma for deep and complicated fistulas in Crohn's disease, followed by a rectal advancement flap, may result in closing of the stoma in 47% of the time. The risk of permanent fecal diversion was substantial in patients with complicated perianal Crohn's disease, with patients requiring a colorectal resection or suffering from fecal incontinence carrying a particularly high risk for permanent fecal diversion. In contrast, patients with perianal Crohn's disease who required surgery for small bowel disease or a segmental colon resection carried no risk of a permanent stoma.}, }
@article {pmid17434363, year = {2007}, author = {McNevin, MS and Lee, PY and Bax, TW}, title = {Martius flap: an adjunct for repair of complex, low rectovaginal fistula.}, journal = {American journal of surgery}, volume = {193}, number = {5}, pages = {597-9; discussion 599}, doi = {10.1016/j.amjsurg.2007.01.009}, pmid = {17434363}, issn = {1879-1883}, mesh = {Adolescent ; Adult ; Digestive System Surgical Procedures/methods ; Female ; Gynecologic Surgical Procedures/methods ; Humans ; Middle Aged ; Rectovaginal Fistula/*surgery ; Retrospective Studies ; *Surgical Flaps ; }, abstract = {BACKGROUND: Complex, rectovaginal fistula (RVF) are uncommon but difficult therapeutic problems. Local repair and flap advancement techniques have a high incidence of recurrence with poor functional outcomes. Transperineal repair with anal sphincter reconstruction, when indicated, and placement of a Martius flap (bulbocavernosus pedicled transplant) result in improved rates of repair and better functional outcomes.<br><br>METHODS: A consecutive series of patients were retrospectively reviewed from a prospective database between 2002 and 2006. Data were gathered from 2 colon- and rectal-specialty practices. Patient demographics and operative and functional outcomes were documented.<br><br>RESULTS: Sixteen patients with a mean age of 39.5 years (17-62) were treated. Etiology of the fistula was obstetric (9), cryptoglandular (5), and Crohn's disease (2). They had undergone a mean of 1.5 (0-4) prior repairs, and 6 had a preexisting diverting stoma before repair. Preoperatively, anal sphincter disruption was identified in 11 patients, and fecal incontinence was identified in 5 patients all with anal sphincter disruption. Dyspareunia was identified in 1 of 13 sexually active patients preoperatively. At a mean follow-up of 75 weeks (24-190), 1 recurrent fistula was identified (6.2%). Stomas were reversed in all patients. Two patients complained of fecal incontinence postoperatively. Five patients had dyspareunia postoperatively (5/16, 31%). One patient had a labial wound complication requiring local wound care.<br><br>CONCLUSION: Selected complex RVF can be reliably repaired with good functional outcomes using the Martius flap with anal sphincter reconstruction. Persistent or recurrent fecal incontinence and dyspareunia are common sequela of the underlying perineal injury and repair. No acute or delayed morbidity related to the Martius flap was identified.}, }
@article {pmid17434285, year = {2007}, author = {Jacquemin, E}, title = {[Screening for biliary atresia and stool color: method of colorimetric scale].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {36}, number = {6 Pt 2}, pages = {945-948}, doi = {10.1016/j.lpm.2007.03.018}, pmid = {17434285}, issn = {0755-4982}, mesh = {Biliary Atresia/*diagnosis ; *Colorimetry ; Feces/*chemistry ; Humans ; *Mass Screening ; }, abstract = {Biliary atresia is a rare disease, but it is the major cause of neonatal cholestasis and the major indication for liver transplantation in children. Kasaï procedure can restore bile flow and prevent or slow progression of disease in a proportion of patients. Data show that the earlier the Kasaï procedure is performed, the better is the outcome. Therefore, rapid referral to an experienced center, for prompt diagnosis and surgery, is strongly recommended. Unfortunately, the disease is often detected late and Kasaï procedure is performed after 60 days of age. In an attempt to achieve earlier diagnosis and better outcome of Kasaï procedure, we propose to institute routine screening for biliary atresia using a stool colorometric scale. This should help to identify earlier children who have acholic stools and may have biliary atresia. We postulate that this screening method will allow to improve the results of the Kasaï procedure and provide children with the best chance of survival with their native liver.}, }
@article {pmid17427562, year = {2007}, author = {Aksoy, U and Tuncay, S}, title = {[Short communication: investigation of intestinal coccidia in patients with diarrhea].}, journal = {Mikrobiyoloji bulteni}, volume = {41}, number = {1}, pages = {127-131}, pmid = {17427562}, issn = {0374-9096}, mesh = {Animals ; Coccidiosis/epidemiology/*parasitology ; Cryptosporidium/isolation &amp; purification ; Cyclospora/isolation &amp; purification ; Diarrhea/epidemiology/*parasitology ; Feces/parasitology ; Female ; Humans ; Immunocompetence ; Immunocompromised Host ; Intestinal Diseases, Parasitic/epidemiology/*parasitology ; Isospora/isolation &amp; purification ; Male ; Prevalence ; Turkey/epidemiology ; }, abstract = {The intestinal protozoa have been increasingly identified in immunocompromised patients. In this study, stool samples of 554 patients [288 male, 266 female; 11 (2%) of them were immunocompromised] with diarrhea were examined between June 2004 and June 2005 in the Parasitology Laboratory of Dokuz Eylul University Hospital, Izmir, Turkey, in order to investigate the prevalence of intestinal coccidia. After formalin-ethyl acetate sedimentation procedure, the samples were examined by both native lugol and Kinyoun acid-fast staining methods for the detection of Cryptosporidium, Cyclospora and Isospora spp. As a result, Isospora belli oocysts were detected in the stool samples of two patients (0.4%) of which one was HIV positive and the other had experienced liver transplantation. Seven (1.3%) and two (0.4%) of the immunocompetent subjects were found positive for Cryptosporidium spp. and for Cyclospora cayetanensis, respectively. In conclusion, Isospora is one of the important protozoa which should be taken into consideration by clinicians in the immunocompromised patients with diarrhea.}, }
@article {pmid17426063, year = {2007}, author = {David, S and Kirchhoff, T and Haller, H and Meier, M}, title = {Heavy metal--rely on gut feelings: novel diagnostic approach to test drug compliance in patients with lanthanum intake.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {22}, number = {7}, pages = {2091-2092}, doi = {10.1093/ndt/gfm208}, pmid = {17426063}, issn = {0931-0509}, mesh = {Colon/*diagnostic imaging ; Feces/chemistry ; Female ; Humans ; Kidney Failure, Chronic/therapy ; Lanthanum/*therapeutic use ; Middle Aged ; *Patient Compliance ; Phosphates/*blood ; *Radiography, Abdominal ; Renal Dialysis/adverse effects ; *Tomography, X-Ray Computed ; }, }
@article {pmid17417664, year = {2007}, author = {Myers, GD and Bollard, CM and Wu, MF and Weiss, H and Rooney, CM and Heslop, HE and Leen, AM}, title = {Reconstitution of adenovirus-specific cell-mediated immunity in pediatric patients after hematopoietic stem cell transplantation.}, journal = {Bone marrow transplantation}, volume = {39}, number = {11}, pages = {677-686}, doi = {10.1038/sj.bmt.1705645}, pmid = {17417664}, issn = {0268-3369}, mesh = {Adenoviridae/genetics/*isolation &amp; purification ; Adenovirus Infections, Human/*immunology/prevention &amp; control ; Adolescent ; Adult ; Child ; Child, Preschool ; DNA, Viral/*analysis/blood ; Feces/virology ; Graft vs Host Disease/prevention &amp; control ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Immunity, Cellular/*immunology ; Infant ; Polymerase Chain Reaction ; Prospective Studies ; T-Lymphocytes/immunology ; Transplantation, Homologous ; }, abstract = {Adenovirus (adv) is a significant cause of morbidity and mortality in pediatric hematopoietic stem cell transplant recipients, and control of infection seems to require antigen-specific T cells. We evaluated the recovery of adv-specific cellular immunity in this patient population related to degree of T-cell immunosuppressive therapy and compared this to adv cellular immunity of normal donors. Over 12 months, we monitored for adv DNA in stool and blood of patients and in the blood of a normal donor group. Twenty-two pediatric hematopoietic stem cell transplant (HSCT) patients (14 months-20 years) who received matched-related (MRD n=6), mismatched related (Haplo n=6) or matched unrelated donor (MUD n=10) grafts, were followed and results compared to healthy controls (n=8). Adv was detected by polymerase chain reaction in blood and/or stool from 81.8% of patients on at least one occasion post-HSCT, but only 68% of patients developed symptomatic adv infections. Recovery of adv-specific T cells was significantly delayed in the MUD and Haplo recipients, whereas recovery in the MRD group was similar to levels detected in healthy donors within 30 days post-transplant. In conclusion, recipients of alternative donor transplants at our institution have significantly delayed adv-specific cellular immune recovery, which correlates to an increased risk of adv-associated morbidity and mortality.}, }
@article {pmid17364883, year = {2007}, author = {Katoh, M and Yokoi, T}, title = {Application of chimeric mice with humanized liver for predictive ADME.}, journal = {Drug metabolism reviews}, volume = {39}, number = {1}, pages = {145-157}, doi = {10.1080/03602530601021340}, pmid = {17364883}, issn = {0360-2532}, mesh = {Animals ; Hepatocytes/enzymology/transplantation ; Humans ; Liver/cytology/drug effects/*metabolism ; Metabolic Detoxication, Phase I ; Metabolic Detoxication, Phase II ; Mice ; Pharmaceutical Preparations/*metabolism ; Transplantation Chimera/*metabolism ; Xenobiotics/metabolism/*pharmacokinetics ; }, abstract = {Much effort to extrapolate the in vivo pharmacokinetics of drugs in human from experimental animals or in vitro studies has been made by many researchers. A urokinase-type plasminogen activator+/+/severe combined immunodeficient transgenic mouse line, in which the liver could be replaced by more than 80% with human hepatocytes, was established recently in Japan. This chimeric mouse line is remarkable because the replacement is higher than any other chimeric mouse reported previously. Since the liver is the critical organ involved in the pharmacokinetics of drugs, human liver is essential for the development of new drugs. To predict the human drug metabolism and pharmacokinetics, human hepatocytes and liver microsomes are recognized as better tools and are frequently used. Thus, chimeric mice with humanized liver would have great advantages in studies on drug metabolism and pharmacokinetics. We have evaluated chimeric mice for studies on absorption, distribution, metabolism, and excretion (ADME). In the liver of the chimeric mice, human phase I and phase II enzymes were clarified to be expressed and to have a similar drug metabolizing capacity as the donor. Human specific metabolites could be detected in the serum, suggesting that the chimeric mice might be used as a human ADME model for both in vitro and in vivo studies. For predicting human drug interactions, enzyme induction and inhibition are serious problems. By the treatment with typical inducers, human CYP1A2 and CYP3A4 expressed in the liver of the chimeric mice had induction potencies. After the treatment with quinidine, a specific inhibitor of human CYP2D6, the area under the curve (AUC) of a CYP2D6 metabolite, 4'-hydroxydebrisoquin, was significantly decreased in the chimeric mice but not in the control mice. Therefore, it was indicated that the chimeric mice could be used for assessing the drug interactions via enzyme induction and inhibition. As well as drug metabolism, the drug excretion was demonstrated to be humanized because cefmetazole was mainly excreted in urine both in the chimeric mice and human but in feces in control uPA-/-/SCID mice. In this review, basic researches on ADME in the chimeric mice with humanized liver are summarized and the application of the chimeric mice for predictive ADME is proposed.}, }
@article {pmid17351646, year = {2007}, author = {Rolston, KV and Jiang, Y and Matar, M}, title = {VRE fecal colonization/infection in cancer patients.}, journal = {Bone marrow transplantation}, volume = {39}, number = {9}, pages = {567-568}, doi = {10.1038/sj.bmt.1705639}, pmid = {17351646}, issn = {0268-3369}, mesh = {APACHE ; Adult ; Aged ; *Enterococcus ; Female ; Graft vs Host Disease/etiology/microbiology/mortality ; Gram-Positive Bacterial Infections/drug therapy/etiology/*mortality ; Hematologic Neoplasms/complications/microbiology/*mortality/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Transplantation, Autologous ; Transplantation, Homologous ; *Vancomycin Resistance ; }, }
@article {pmid17332112, year = {2007}, author = {Gilbert, TW and Stewart-Akers, AM and Simmons-Byrd, A and Badylak, SF}, title = {Degradation and remodeling of small intestinal submucosa in canine Achilles tendon repair.}, journal = {The Journal of bone and joint surgery. American volume}, volume = {89}, number = {3}, pages = {621-630}, doi = {10.2106/JBJS.E.00742}, pmid = {17332112}, issn = {0021-9355}, support = {EB000506/EB/NIBIB NIH HHS/United States ; }, mesh = {Achilles Tendon/cytology/injuries/*physiology ; Animals ; Carbon Radioisotopes ; Dogs ; Extracellular Matrix/physiology/*transplantation ; Intestinal Mucosa/cytology/*transplantation ; Intestine, Small/cytology ; Models, Animal ; Swine ; Transplantation, Heterologous ; }, abstract = {BACKGROUND: Extracellular matrix derived from porcine small intestinal submucosa is used for the repair of musculotendinous tissues. Preclinical evaluation and clinical use have suggested that small intestinal submucosa extracellular matrix degrades rapidly after implantation and can be replaced by host tissue that is functionally and histologically similar to the normal tissue.<br><br>METHODS: The present study analyzed the temporal degradation of a ten-layer multilaminate device of small intestinal submucosa extracellular matrix used for the repair of canine Achilles tendon and examined the corresponding histological appearance of the remodeled tissue during the course of scaffold degradation. Devices were fabricated from small intestinal submucosa extracellular matrix labeled with 14C. The amount of 14C remaining in the remodeled graft was measured by liquid scintillation counting at three, seven, fourteen, twenty-eight, sixty, and ninety days after surgery. Blood, urine, feces, and other parenchymal tissues were also harvested to determine the fate of scaffold degradation products. Tissue specimens were prepared for routine histological analysis to examine the morphology of the remodeled graft at each time-point.<br><br>RESULTS: The small intestinal submucosa extracellular matrix graft degraded rapidly, with approximately 60% of the mass lost by one month after surgery, and the graft was completely resorbed by three months after surgery. The graft supported rapid cellular infiltration and host tissue ingrowth. By ninety days after surgery, the remodeled small intestinal submucosa extracellular matrix consisted of a dense collagenous tissue with organization, cellularity, and vascularity similar to that of normal tendon.<br><br>CONCLUSIONS: Small intestinal submucosa extracellular matrix is rapidly degraded after implantation for the repair of a musculotendinous tissue in this canine Achilles tendon repair model and is replaced by the deposition and organization of host tissue that is histologically similar to that of normal tissue.}, }
@article {pmid17330203, year = {2007}, author = {Schwabegger, AH and Kronberger, P and Obrist, P and Brath, E and Miko, I}, title = {Functional sphincter ani externus reconstruction for treatment of fecal stress incontinence using free latissimus dorsi muscle transfer with coaptation to the pudendal nerve: preliminary experimental study in dogs.}, journal = {Journal of reconstructive microsurgery}, volume = {23}, number = {2}, pages = {79-85}, doi = {10.1055/s-2007-970187}, pmid = {17330203}, issn = {0743-684X}, mesh = {Anal Canal/pathology/*surgery ; Animals ; Disease Models, Animal ; Dogs ; Feasibility Studies ; Fecal Incontinence/*surgery ; Female ; Muscle, Skeletal/*transplantation ; Peripheral Nerves ; *Plastic Surgery Procedures ; *Surgical Flaps ; }, abstract = {The external anal sphincter (EAS) is a skeletal muscle capable of voluntary contraction to prevent accidental defecation. Current reconstructive options for a severely damaged EAS using local muscle flaps are not always adequate for functional repair. The present preliminary experimental model was designed to assess the feasibility of a neuromicrovascular latissimus dorsi muscle transfer for functional external spincter muscle reconstruction. In nine mongrel dogs, the anal sphincter muscles were totally resected, leaving a mucosal canal in place. A segmental latissimus dorsi muscle was shaped around the anal canal in a circular fashion, with coaptation to the pudendal nerve, and vessel anastomosis at the ischiorectal fossa. Functional evaluation was performed using electromyogram, sphincter manometry, video documentation, and histologic examination with standard and immunohistochemical staining. After 8 months, the remaining three eligible dogs were continent. Muscle function was verified by means of electromyogram, sphincter manometry, and a video record. Histologic and immunohistochemical examination confirmed the functional results, showing only minor zones of fatty and fibrous degeneration. Transplantation of a segmental latissimus dorsi muscle with vascular anastomosis and coaptation to the pudendal nerve has proved to be successful in restoring (voluntary) anal continence experimentally in dogs. Its feasibility for perfect orientation as a neosphincter seems to be superior to any pedicled muscle flap. However, these preliminary results deserve further investigation prior to considering application in humans.}, }
@article {pmid17317293, year = {2007}, author = {Kroes, AC and de Klerk, EP and Lankester, AC and Malipaard, C and de Brouwer, CS and Claas, EC and Jol-van der Zijde, EC and van Tol, MJ}, title = {Sequential emergence of multiple adenovirus serotypes after pediatric stem cell transplantation.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {38}, number = {4}, pages = {341-347}, doi = {10.1016/j.jcv.2007.01.001}, pmid = {17317293}, issn = {1386-6532}, mesh = {Adenoviridae/*classification/*isolation &amp; purification ; Adenoviridae Infections/mortality/*virology ; Adolescent ; Adult ; Child ; Child, Preschool ; DNA, Viral/chemistry/genetics ; Feces/virology ; Female ; Hematologic Diseases/*complications ; Humans ; Infant ; Male ; Neutralization Tests ; Sequence Analysis, DNA ; Serotyping ; *Stem Cell Transplantation ; Survival Analysis ; Virus Cultivation ; }, abstract = {BACKGROUND: Adenovirus infections after allogeneic stem cell transplantation (SCT), particularly in children, may be severe and protracted. Up to 51 different serotypes of adenovirus are presently recognized but serotyping is usually limited to initial viral isolates.<br><br>OBJECTIVES: A systematic and sustained analysis of adenovirus serotypes in a cohort of adenovirus-infected pediatric SCT recipients, correlated to transplant-associated variables.<br><br>STUDY DESIGN: Eighty-three consecutive pediatric SCT recipients were studied by culture of feces and adenoviruses isolated were serotyped by neutralization. Upon persistent viral excretion, serotyping was repeated for at least two isolates of any infectious episode, including initial and final isolates, and patients with single and multiple serotypes were compared. In a subset of cases, serotyping of fecal isolates was compared to genotypic analysis.<br><br>RESULTS: In 33 patients, adenovirus was isolated at least once after SCT. Serotyping uncovered 49 different adenoviruses, including three isolates without an assigned serotype. In 16 patients, a single serotype was present for a sustained period, whereas 12 patients (36%) showed multiple serotypes. Comparison of these groups demonstrated more frequent non-malignant primary disease with multiple infections (p<0.01), but otherwise no significant differences were observed, although single serotype infections had a lower survival rate. Remarkably, serotype 31 appeared initially in 7 out of 12 patients with multiple infections. Genotyping by sequencing confirmed neutralization assays at least at the species level in 14 of 18 isolates.<br><br>CONCLUSION: In 36% of adenovirus infections after SCT more than one serotype could be detected by sequential analysis. Multiple serotypes occurred more often with non-malignant disorders. Adenovirus serotype 31 was often included. This finding is relevant for diagnostic purposes and immunotherapeutic interventions and provides insight into the pathogenesis of this problem.}, }
@article {pmid17309003, year = {2007}, author = {Altomare, DF and Rinaldi, M and Rubini, D and Rubini, G and Portincasa, P and Vacca, M and Artor, NA and Romano, G and Memeo, V}, title = {Long-term functional assessment of antegrade colonic enema for combined incontinence and constipation using a modified Marsh and Kiff technique.}, journal = {Diseases of the colon and rectum}, volume = {50}, number = {7}, pages = {1023-1031}, doi = {10.1007/s10350-006-0863-0}, pmid = {17309003}, issn = {0012-3706}, mesh = {Adult ; Aged ; Colon ; Colostomy ; *Constipation/complications/physiopathology/therapy ; Defecation/*physiology ; Enema/*methods ; *Fecal Incontinence/complications/physiopathology/therapy ; Female ; Follow-Up Studies ; Gallbladder Emptying/*physiology ; Gastric Emptying/*physiology ; Gastrointestinal Transit/*physiology ; Humans ; Male ; Middle Aged ; Pressure ; Recovery of Function ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE: Constipation and fecal incontinence can severely affect quality of life for patients, particularly when simultaneously present. Malone antegrade colonic enema enables periodic colonic emptying, thus preventing uncontrolled passage of feces and constipation.<br><br>METHODS: Eleven patients with fecal incontinence and severe constipation or perineal colostomy after Miles' operation underwent a modified Marsh and Kiff ileostomy for antegrade colonic enema. Before and after surgery, the patients were fully evaluated for gastrointestinal functions, including gallbladder and stomach emptying time, H(2)-breath test, colonic transit time, dynamic defecography, and anorectal manometry. The severity of incontinence and constipation was scored preoperatively and postoperatively by using the American Medical System score and Cleveland Clinic Constipation scale, respectively, whereas the quality of life was measured by the Gastrointestinal Quality of Life Index. The surgical technique involved division of the terminal ileum 10 to 15 cm from the ileocecal valve, anastomosis and intussusception of the ileum with the cecum, narrowing of the ileal conduit with a linear stapler, and a small, introflexed ileostomy with an advanced skin flap.<br><br>RESULTS: During the postoperative period, the mean American Medical System score decreased significantly from 77 to 11 (P<0.01) and the mean Cleveland Clinic Constipation score from 23 to 8.5 (P<0.01) with a significant improvement of quality of life. Antegrade colonic enema did not affect gallbladder, gastric, or orocecal transit time, which remained comparable with baseline. Colonic scintigraphy showed that antegrade colonic enema was efficient to clean the whole colon and rectum, leaving only 24 (range, 6-40) percent of the initial radioactivity after 30 minutes. Ileal manometry confirmed the presence of a high-pressure zone, preventing accidental reflux.<br><br>CONCLUSIONS: Modified Marsh and Kiff technique is a safe and effective surgical option to treat patients with combined fecal incontinence and severe constipation and those with perineal colostomy after Miles. It should be recommended as a last option before colostomy.}, }
@article {pmid17279003, year = {2007}, author = {Sivaprakasam, P and Carr, TF and Coussons, M and Khalid, T and Bailey, AS and Guiver, M and Mutton, KJ and Turner, AJ and Grainger, JD and Wynn, RF}, title = {Improved outcome from invasive adenovirus infection in pediatric patients after hemopoietic stem cell transplantation using intensive clinical surveillance and early intervention.}, journal = {Journal of pediatric hematology/oncology}, volume = {29}, number = {2}, pages = {81-85}, doi = {10.1097/MPH.0b013e318030875e}, pmid = {17279003}, issn = {1077-4114}, mesh = {Adenovirus Infections, Human/drug therapy/*etiology/*immunology ; Adolescent ; Antiviral Agents/therapeutic use ; Blood/virology ; Bronchoalveolar Lavage Fluid/virology ; Child ; Cidofovir ; Cytosine/analogs &amp; derivatives/therapeutic use ; Feces/virology ; Female ; Fluorescent Antibody Technique ; Graft vs Host Disease/etiology/prevention &amp; control ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Immunocompromised Host ; Immunosuppression Therapy/adverse effects ; Infant ; Male ; Microscopy, Electron, Transmission ; Organophosphonates/therapeutic use ; Reverse Transcriptase Polymerase Chain Reaction ; Ribavirin/therapeutic use ; }, abstract = {Adenovirus is a common cause of morbidity and mortality after hemopoietic stem cell transplantation in children. Recently the incidence, risk factors, and outcome of such infections have been better defined using improved virologic detection methods, in particular polymerase chain reaction. We have introduced intensive virologic surveillance for adenovirus in our institution including at least weekly polymerase chain reaction testing of blood and stool samples. We report on 71 prospectively monitored transplants, including 40 from unrelated donors. In total, there were 8 cases of invasive adenovirus infection, 3 of whom died. Mortality was less than in previous studies as cases were managed with antiviral chemotherapy and reduction of immune suppression. In fatal cases, there was concurrent difficult graft versus host disease making withdrawal of immune suppression therapy impossible. We describe 2 cases of graft failure in association with adenovirus viremia and its treatment that were successfully managed with further donor cell infusion.}, }
@article {pmid17276661, year = {2007}, author = {Jacquemin, E}, title = {[Screening for biliary atresia and stool colour: Method of colorimetric scale].}, journal = {Archives de pediatrie : organe officiel de la Societe francaise de pediatrie}, volume = {14}, number = {3}, pages = {303-305}, doi = {10.1016/j.arcped.2006.12.015}, pmid = {17276661}, issn = {0929-693X}, mesh = {Biliary Atresia/*diagnosis ; Color ; *Feces ; Humans ; Infant, Newborn ; }, abstract = {Biliary atresia is a rare disease, but it is the major cause of neonatal cholestasis and the major indication for liver transplantation in children. Kasaï procedure can restore bile flow and prevent or slow progression of disease in a proportion of patients. Data show that the earlier the Kasaï procedure is performed, the better is the outcome. Therefore, rapid referral to an experienced centre, for prompt diagnosis and surgery, is strongly recommended. Unfortunately, the disease is often detected late, and Kasaï procedure is performed after 60 days of age. In an attempt to achieve earlier diagnosis and better outcome of Kasaï procedure, we propose to institute routine screening for biliary atresia using a stool colorimetric scale. This should help to identify earlier children who have acholic stools and may have biliary atresia. We postulate that this screening method will allow improving the results of the Kasaï procedure and providing children with the best chance of survival with their native liver.}, }
@article {pmid17245720, year = {2007}, author = {Takayama, R and Hatakeyama, N and Suzuki, N and Yamamoto, M and Hayashi, T and Ikeda, Y and Ikeda, H and Nagano, H and Ishida, T and Tsutsumi, H}, title = {Quantification of adenovirus species B and C viremia by real-time PCR in adults and children undergoing stem cell transplantation.}, journal = {Journal of medical virology}, volume = {79}, number = {3}, pages = {278-284}, doi = {10.1002/jmv.20796}, pmid = {17245720}, issn = {0146-6615}, mesh = {Adenoviridae/classification/*isolation &amp; purification ; Adenoviridae Infections/epidemiology/physiopathology/*virology ; Adolescent ; Adult ; Child ; Child, Preschool ; DNA, Viral/analysis ; Feces/virology ; Female ; Hematologic Diseases/*complications/therapy ; Humans ; Infant ; Male ; Middle Aged ; Molecular Epidemiology ; Polymerase Chain Reaction/*methods ; *Stem Cell Transplantation ; Urine/virology ; *Viral Load ; *Viremia ; }, abstract = {Adenovirus infection during stem cell transplantation is associated with high morbidity and mortality. Adenovirus species B and C have been the main causes for these infections; however, epidemiological details about the species are still unclear. To clarify the contributions of species B and C adenovirus, the DNA was tested serially by quantitative real-time PCR in peripheral blood, stool and urine of 32 patients (16 adults and 16 children) undergoing stem cell transplantation. Adenovirus species B viremia was detected in 10 of 16 adult and 6 of 16 pediatric transplant recipients. Adenovirus species C viremia was also detected simultaneously in five adult and three pediatric recipients. The stool and urine of patients with adenovirus viremia were also positive for the same adenovirus species as in blood. In contrast, in none of 50 healthy adult controls was adenovirus species B or C viremia detected. Among patients who developed adenovirus viremia, one adult recipient developed disseminated disease and died from multiple organ failure. The remaining patients experienced fever of several degrees and/or diarrhea during the period of adenovirus viremia; however, they all recovered without antiviral therapy. The results indicated that stem cell transplantation was frequently associated with adenovirus species B or C viremia, although it did not always cause serious infectious complications.}, }
@article {pmid17237431, year = {2007}, author = {Bamias, G and Okazawa, A and Rivera-Nieves, J and Arseneau, KO and De La Rue, SA and Pizarro, TT and Cominelli, F}, title = {Commensal bacteria exacerbate intestinal inflammation but are not essential for the development of murine ileitis.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {178}, number = {3}, pages = {1809-1818}, doi = {10.4049/jimmunol.178.3.1809}, pmid = {17237431}, issn = {0022-1767}, support = {DK-42191/DK/NIDDK NIH HHS/United States ; DK-44540/DK/NIDDK NIH HHS/United States ; DK-55812/DK/NIDDK NIH HHS/United States ; DK-67629/DK/NIDDK NIH HHS/United States ; }, mesh = {Adoptive Transfer ; Animals ; Bacteria/*pathogenicity ; CD4-Positive T-Lymphocytes/transplantation ; Chemotaxis, Leukocyte ; Crohn Disease ; Cytokines ; Forkhead Transcription Factors/genetics ; Ileitis/*etiology/pathology ; Inflammation/*microbiology ; Intestines/microbiology/*pathology ; Lymph Nodes ; Mice ; Mice, SCID ; Mucous Membrane/immunology ; T-Lymphocytes, Regulatory/cytology ; Th2 Cells ; }, abstract = {The pathogenesis of Crohn's disease has been associated with a dysregulated response of the mucosal immune system against intraluminal Ags of bacterial origin. In this study, we have investigated the effects of germfree (GF) conditions in the SAMP1/YitFc murine model of Crohn's disease-like ileitis. We show that the bacterial flora is not essential for ileitis induction, because GF SAMP1/YitFc mice develop chronic ileitis. However, compared with disease in specific pathogen-free (SPF) mice, ileitis in GF mice is significantly attenuated, and is associated with delayed lymphocytic infiltration and defective mucosal expression of Th2 cytokines. In addition, we demonstrate that stimulation with purified fecal Ags from SPF, but not GF mice leads to the generation of IL-4-secreting effector lymphocytes. This result suggests that commensal bacteria drive Th2 responses characteristic of the chronic phase of SAMP1/YitFc ileitis. Finally, adoptive transfer of CD4-positive cells from GF, but not SPF mice induces severe colitis in SCID recipients. These effects were associated with a decreased frequency of CD4(+)CD25(+)Foxp3(+) T cells in the mesenteric lymph nodes of GF mice compared with SPF mice, as well as lower relative gene expression of Foxp3 in CD4(+)CD25(+) T cells in GF mice. It is therefore apparent that, in the absence of live intraluminal bacteria, the regulatory component of the mucosal immune system is compromised. All together, our results indicate that in SAMP1/YitFc mice, bacterial flora exacerbates intestinal inflammation, but is not essential for the generation of the chronic ileitis that is characteristic of these mice.}, }
@article {pmid17227244, year = {2006}, author = {López, T and Almirall, J and Calvet, X and Quesada, M and Sanfeliú, I and Segura, F and García, M}, title = {[Helicobacter pylori does not contribute to iron deficiency in hemodialysis patients].}, journal = {Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia}, volume = {26}, number = {6}, pages = {673-678}, pmid = {17227244}, issn = {0211-6995}, mesh = {Aged ; Anemia, Iron-Deficiency/drug therapy/*etiology ; Comorbidity ; Dyspepsia/etiology ; Erythropoietin/therapeutic use ; Female ; Ferritins/blood ; Helicobacter Infections/*complications/diagnosis/epidemiology ; Helicobacter pylori/*pathogenicity ; Hematocrit ; Humans ; Iron/blood ; Kidney Failure, Chronic/*complications/therapy ; Male ; Middle Aged ; Prevalence ; Renal Dialysis/*adverse effects ; Transferrin/analysis ; }, abstract = {BACKGROUND: Many studies in the general population have shown a link between Helicobacter pylori infection and iron-deficiency, often resulting in iron-deficient anaemia. Despite the high prevalence of iron deficiency in hemodialysis patients, no studies have been performed in this population.<br><br>OBJECTIVE: To evaluate the role of Helicobacter pylori infection in the appearance of anemia and the iron requirements in our hemodialysis population.<br><br>MATERIAL AND METHODS: After excluding patients with severe pathology and short life expectancy and those with blood losses secondary to other causes, 79 patients were included.Iron requirements and anaemia were determined by iron serum, ferritin, and hematocrit values; and by transfusion, eritropoietin and iron requirements. The diagnosis of Helicobacter pylori status was established by the concordance of at least two of the three non invasive diagnostic methods performed (breath test, serology and fecal antigen of Helicobacter pylori).<br><br>RESULTS: Prevalence of Helicobacter pylori infection was 43%. No significant differences between patients infected or not by Helicobacter pylori were found in any of the variables analysed: hematocrit (33.5% versus 34.1%), serum iron (58.9 versus 63.7 pg/dl), ferritin(340.3 versus 264.2 ng/ml), transferrin saturation index (22.5% versus 25.2%), dose of eritropoietin administered (96.6 versus 93.5 U/kg/weekly), and parenteral iron (1,389 versus 1,538 mg/year). A noteworthy finding was that patients with Helicobacter pylori infection had been on hemodialysis for a shorter period than those without (37.4 versus 63.7 months,p = 0.04).<br><br>CONCLUSION: Helicobacter pylori infection has no effect on anaemia (hematocrit, Eritropoietin dose or iron needs) in our hemodialysis patients. Prevalence of Helicobacter pylori is lower in patients with longer time on dialysis. We consider that the diagnosis of Helicobacter pylori infection must be reserved for clinical peptic ulcer suspicion or patients on transplant waiting list.}, }
@article {pmid17225210, year = {2007}, author = {Hahnloser, D and Pemberton, JH and Wolff, BG and Larson, DR and Crownhart, BS and Dozois, RR}, title = {Results at up to 20 years after ileal pouch-anal anastomosis for chronic ulcerative colitis.}, journal = {The British journal of surgery}, volume = {94}, number = {3}, pages = {333-340}, doi = {10.1002/bjs.5464}, pmid = {17225210}, issn = {0007-1323}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anal Canal/*physiopathology/surgery ; Analysis of Variance ; Anastomosis, Surgical ; Child ; Colitis, Ulcerative/physiopathology/*surgery ; Colonic Pouches/*physiology/standards ; Fecal Incontinence/etiology/physiopathology ; Female ; Follow-Up Studies ; Humans ; Ileum/*surgery ; Male ; Middle Aged ; Postoperative Complications/etiology/physiopathology ; Proctocolectomy, Restorative/*standards ; Prospective Studies ; *Quality of Life ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is performed routinely for chronic ulcerative colitis.<br><br>METHODS: Using data from a prospective database and annual standardized questionnaires, functional outcome, complications and quality of life (QoL) after IPAA were assessed.<br><br>RESULTS: Some 1885 IPAA operations were performed for chronic ulcerative colitis over a 20-year period (mean follow-up 11 years). The mean age at the time of IPAA was 34.1 years, increasing from 31.2 years (1981-1985) to 36.3 years (1996-2000). The overall rate of pouch success at 5, 10, 15 and 20 years was 96.3, 93.3, 92.4 and 92.1 per cent respectively. Mean daytime stool frequency increased from 5.7 at 1 year to 6.4 at 20 years (P < 0.001), and also increased at night (from 1.5 to 2.0; P < 0.001). The incidence of frequent daytime faecal incontinence increased from 5 to 11 per cent during the day (P < 0.001) and from 12 to 21 per cent at night (P < 0.001). QoL remained unchanged and 92 per cent remained in the same employment. Seventy-six patients were eventually diagnosed with indeterminate colitis and 47 with Crohn's disease.<br><br>CONCLUSION: IPAA is a reliable surgical procedure for patients requiring proctocolectomy for chronic ulcerative colitis and indeterminate colitis. The clinical and functional outcomes are excellent and stable for 20 years after operation.}, }
@article {pmid17224495, year = {2007}, author = {Hetzer, FH and Hahnloser, D and Clavien, PA and Demartines, N}, title = {Quality of life and morbidity after permanent sacral nerve stimulation for fecal incontinence.}, journal = {Archives of surgery (Chicago, Ill. : 1960)}, volume = {142}, number = {1}, pages = {8-13}, doi = {10.1001/archsurg.142.1.8}, pmid = {17224495}, issn = {0004-0010}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Fecal Incontinence/*surgery ; Female ; Health Status Indicators ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; Morbidity ; Postoperative Period ; *Prostheses and Implants ; *Quality of Life ; Treatment Outcome ; }, abstract = {HYPOTHESIS: Permanent sacral nerve stimulation (SNS) is a promising emerging treatment for fecal incontinence. However, there is little data on morbidity and quality of life (QOL) during long-term stimulation.<br><br>DESIGN: Prospective trial to assess morbidity and QOL in patients treated with SNS. Median follow-up was 13 months (range, 1-42 months).<br><br>SETTING: University hospital providing primary, secondary, and tertiary care.<br><br>PATIENTS: Between December 2001 and July 2005, SNS was tested in 44 patients (30 women), with a median age of 65 years (range, 15-88 years).<br><br>INTERVENTIONS: Percutaneous nerve evaluation and permanent insertion of an implantable pulse generator.<br><br>MAIN OUTCOME MEASURES: Morbidity, stool diary, and Wexner Score for fecal incontinence; Hanley Score for urinary incontinence; and Gastrointestinal Quality of Life Index, the 36-item short form health survey, and the Royal London Hospital questionnaire for QOL.<br><br>RESULTS: A permanent stimulator was implanted in 37 patients (84%). Eight patients (22%) experienced complications that required surgical intervention. (A successful restimulation was possible for 5 of those patients.) Adverse effects of SNS were remedied in 5 patients by reprogramming the stimulator. Wexner Scores decreased from a median of 16 points preoperatively (range, 6-20), to a median of 5 points postoperatively (range, 0-13; P<.001). The median number of involuntary stool losses and for urge defecations also decreased significantly. Significant improvement in QOL was found in both generic and incontinence-specific questionnaires (P<.05). The success rate of SNS was 77% (34 of 44 patients) and 92% (34 of 37) in patients with permanent implantation.<br><br>CONCLUSIONS: The minimally invasive technique of SNS is safe and effective. Most adverse effects can be easily remedied. Our data demonstrate that SNS significantly improves patients' QOL, including their physical and psychological well-being.}, }
@article {pmid17224110, year = {2006}, author = {Rosales-Olivares, LM and Baena-Ocampo, Ldel C and Miramontes-Martínez, VP and Alpízar-Aguirre, A and Reyes-Sánchez, A}, title = {[Aneurysmal bone cyst of the spine. Case report].}, journal = {Cirugia y cirujanos}, volume = {74}, number = {5}, pages = {377-380}, pmid = {17224110}, issn = {0009-7411}, mesh = {Adolescent ; Back Pain/etiology ; Bone Cysts, Aneurysmal/complications/pathology/*surgery ; Bone Transplantation ; Decompression, Surgical/instrumentation/*methods ; Diagnosis, Differential ; Disease Progression ; Fecal Incontinence/etiology ; Female ; Humans ; Internal Fixators ; Kyphosis/etiology ; Osteolysis/etiology ; Paraplegia/etiology ; Paresthesia/etiology ; Spinal Cord Compression/*etiology ; Spinal Diseases/complications/pathology/*surgery ; Spinal Fusion/*methods ; Thoracic Vertebrae/pathology/*surgery ; Urinary Incontinence/etiology ; }, abstract = {The aneurysmal bone cyst (ABC) is a fast-growing tumor of undefined neoplastic nature. It is occasionally an aggressive benign lesion whose treatment of choice is a complete resection, even though the risk of profuse transoperative bleeding exists. We present a female patient with thoracic spine deformity, with progressive paresthesias and muscle weakness of lower extremities that evolved to paralysis of both lower extremities and sphincter incontinence. Based on radiographic films, lytic lesions were identified at T7 to T9 vertebrae as well as medullary space invasion. In electrophysiologic tests, a complete somatosensorial pathway block was reported. Prior to resection of the neoplastic lesion and thoracolumbar stabilization, an incisional biopsy was performed. There was no postoperative medullary functional improvement. Morphological findings corresponded to an aneurysmal bone cyst at T8. This lesion is mainly located in the long bones and less frequently of the spine, where instability and medullary compression may occur. It is possible to confuse this neoplasia with other lesions. Hence, definite diagnosis with biopsy is necessary for determining an adequate therapeutic plan to eradicate recurrence risk or associated neurologic sequelae, as well as to gain proper stability at the involved vertebral segments.}, }
@article {pmid17177057, year = {2007}, author = {Herrera, L and Martínez, C and Carrasco, H and Jansen, AM and Urdaneta-Morales, S}, title = {Cornea as a tissue reservoir of Trypanosoma cruzi.}, journal = {Parasitology research}, volume = {100}, number = {6}, pages = {1395-1399}, pmid = {17177057}, issn = {0932-0113}, mesh = {Animals ; Cornea/*parasitology ; Disease Reservoirs/parasitology/*veterinary ; Mice ; Rodentia/parasitology ; Trypanosoma cruzi/*isolation &amp; purification ; }, abstract = {Trypanosoma cruzi causal agent of Chagas' disease is a paninfective parasite of mammals transmitted through skin fecal contamination by Triatominae vectors. Studies of alternative routes for infection are scarce; therefore, eye infection should be important, because of the eye's high blood irrigation and brain proximity, as port of entry of the parasite. Trypanosoma cruzi parasites and/or their genetic material in ocular and adjacent muscle tissues were studied in batches of six NMRI mice (15 g) and Trichomys apereoides, an ancient caviomorph (250 g) inoculated with T. cruzi metacyclics from Brazilian (2) and Venezuelan (3) isolates genetically typified as T. cruzi I and II. Two animals/batch in the acute or chronic phase were killed and necropsies of cardiac and skeletal muscles, eyeball, and surrounding ocular muscle were processed for hematoxylin-eosine staining. Tissue parasitism was determined. DNA of the digested sections of the eyeball (5-10 mum) was extracted for T. cruzi k-DNA amplification by PCR, with S35 and S36 primers. The PCR products were analyzed. The average of maximum values of parasitemia of all infected animals was of 10(5) trypomastigotes/ml blood. Skeletal muscle and heart were colonized in patent infection for all isolates. Amastigote nests were found in corneal tissue of 2/3 of the used isolates and adjacent ocular muscle and connective tissue were parasitized. Trypanosoma cruzi k-DNA (330-bp band) was observed in ocular tissue of 4/6 of the isolates studied in both animal models. Investigations concerning infection of the eye globe tissues by T. cruzi are extremely scarce. The presence of stages of T. cruzi and/or its genetic products in ocular tissues indicate a broad colonization from a systemic infection. The results show the ocular environment as a possible appropriate microniche for T. cruzi and emphasize the risk of transmitting T. cruzi by ocular fluids and by parasitized cornea through transplants.}, }
@article {pmid17175262, year = {2006}, author = {Watanabe, M and Yuzawa, K and Homma, M and Ohkohchi, N}, title = {Establishment of an animal model with side effects induced by mycophenolate mofetil and pharmacohistological analysis of them.}, journal = {Transplantation proceedings}, volume = {38}, number = {10}, pages = {3323-3326}, doi = {10.1016/j.transproceed.2006.10.162}, pmid = {17175262}, issn = {0041-1345}, mesh = {Animals ; Body Weight/drug effects ; Diarrhea/*chemically induced ; Energy Intake ; Feeding Behavior/drug effects ; Immunosuppressive Agents/adverse effects ; Levofloxacin ; Male ; Mice ; Mice, Inbred BALB C ; Models, Animal ; Mycophenolic Acid/adverse effects/*analogs &amp; derivatives ; Ofloxacin/pharmacology ; Weight Loss/*drug effects ; }, abstract = {UNLABELLED: Mycophenolate mofetil (MMF) is used for immunosuppression after organ transplantation, but gastrointestinal side effects including diarrhea are sometimes observed with this drug. We sought to construct on animal model of diarrhea with MMF in rodents.<br><br>MATERIALS AND METHODS: BALB/Cj mice, weighing 25 g received 500 mg /kg of MMF, 60 mg/kg of levofloxacin (LVFX), 1000 mg/kg of Hangeshashin-to (HST), which is traditional Kampo medicine. This cocktail was administered orally to MMF, LVFX, HST, MMF+LVFX, and MMF+LVFX+HST groups for 21 days. We measured the water content fecal collected on days 1, 4, 8, 11, 14, 18, and 21. Feces on day 21 were cultured for identification of fecal flora. Mice were sacrificed on day 21, with blood samples collected to measure mycophenolic acid (MPA) concentrations by HPLC. Jejunum, cecum, and colon were taken for histological evaluation.<br><br>RESULTS: Significant weight loss of mice and increased fecal water content of were observed in MMF and MMF+LVFX but not in MMF+LVFX+HST groups. Serum MPA levels didn't differ in MMF-administered groups. Inflammatory changes in intestinal villi were observed in the cecum in MMF and MMF+LVFX groups. A change in fecal flora was observed in LVFX-administered groups.<br><br>CONCLUSION: Diarrhea induced by MMF in a rodent model produced inflammatory changes in the cecum. LVFX seemed to change the activity of beta-glucuronidase in the fecal flora. HST suppressed fecal softening induced by MMF in this animal model.}, }
@article {pmid17106849, year = {2006}, author = {Yazar, S and Tokgöz, B and Yaman, O and Sahin, I}, title = {[Isospora belli infection in a patient with a renal transplant].}, journal = {Turkiye parazitolojii dergisi}, volume = {30}, number = {1}, pages = {22-24}, pmid = {17106849}, issn = {1300-6320}, mesh = {Adult ; Animals ; Anti-Infective Agents/therapeutic use ; Feces/parasitology ; Humans ; *Immunocompromised Host ; Immunosuppressive Agents/therapeutic use ; Isospora/*isolation &amp; purification ; Isosporiasis/*diagnosis/drug therapy/parasitology ; Kidney Failure, Chronic/surgery ; Kidney Transplantation/*immunology ; Male ; Oocysts ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use ; }, abstract = {Isospora belli infection is frequent in immunosuppressed patients and can cause wasting diarrhea. We present the first isosporiosis case in a renal transplant recipient from Turkey. The 25-year old male patient who had had a renal transplantation due to renal failure and had received immunosuppressive therapy presented at the hospital complaining of weakness, nausea, vomiting and diarrhea that had lasted for 15 days. Isospora belli oocysts were detected in stool samples by direct microscopy, modified Ziehl-Neelsen staining methods and autofluorescence technique. Oocysts in the stool samples were also sporulated in 2.5% potassium dichromate and the sporulated oocysts were seen microscopically. The patient was treated with co-trimoxazole (trimethoprim 160 mg, sulphamethoxazole 800 mg) every 12 hours for seven days, with elimination of the symptoms at this time. After this, Isospora belli oocysts were no longer seen in stool samples.}, }
@article {pmid17101580, year = {2006}, author = {Walkowiak, J and Jankowska, I and Pawlowska, J and Bull, L and Herzig, KH and Socha, J}, title = {Normal pancreatic secretion in children with progressive familial intrahepatic cholestasis type 1.}, journal = {Scandinavian journal of gastroenterology}, volume = {41}, number = {12}, pages = {1480-1483}, doi = {10.1080/00365520600842344}, pmid = {17101580}, issn = {0036-5521}, mesh = {Adenosine Triphosphatases/genetics ; Adolescent ; Adult ; Child, Preschool ; Cholestasis, Intrahepatic/genetics/*physiopathology ; Chymotrypsin/analysis ; Feces/enzymology ; Female ; Humans ; Lipase/analysis ; Male ; Pancreas, Exocrine/*metabolism ; Pancreatic Elastase/analysis ; }, abstract = {OBJECTIVE: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is a rare, autosomal, recessive, inherited disease resulting from mutations in the ATP8B1 gene which is expressed at high levels in the small intestine and pancreas and at lower levels in the liver. Given this expression pattern, patients might be expected to have a pancreatic phenotype. Although pancreatitis and steatorrhea have been reported in patients with PFIC1, the available data on pancreatic function are not fully convincing. Therefore, the objective of this study was to assess exocrine pancreatic function in patients with PFIC1.<br><br>MATERIAL AND METHODS: Three subjects with a diagnosis of PFIC1 were included in the study. The diagnosis was confirmed by molecular analysis of ATP8B1. Prior to surgical treatment (biliary diversion), two patients had steatorrhea and in the third patient, a borderline value for fecal fat excretion was documented. In one patient, liver transplantation also was subsequently performed. Exocrine pancreatic secretion was assessed by the use of fecal elastase-1 and chymotrypsin tests. Fecal lipase concentrations were determined in order to exclude isolated lipase deficiency. Other typical diagnostic procedures were performed annually.<br><br>RESULTS: The results of the fecal tests were within the normal range. None of the three patients experienced any episodes that could be related to acute or chronic pancreatitis. Laboratory tests including serum amylase and lipase tests were always normal. Abdominal ultrasonography findings did not show any pancreatic pathology.<br><br>CONCLUSIONS: Pancreatic secretion in the study patients with progressive familial intrahepatic cholestasis type 1 was normal. The observed steatorrhea was not related to pancreatic insufficiency.}, }
@article {pmid17086319, year = {2006}, author = {Cardoso, AV and Lescano, SA and Amato Neto, V and Gakiya, E and Santos, SV}, title = {Survival of Trypanosoma cruzi in sugar cane used to prepare juice.}, journal = {Revista do Instituto de Medicina Tropical de Sao Paulo}, volume = {48}, number = {5}, pages = {287-289}, doi = {10.1590/s0036-46652006000500009}, pmid = {17086319}, issn = {0036-4665}, mesh = {Animals ; Chagas Disease/*transmission ; Feces/parasitology ; *Food Parasitology ; Male ; Mice ; Mice, Inbred BALB C ; Saccharum/*parasitology ; Time Factors ; Triatoma/*parasitology ; Trypanosoma cruzi/pathogenicity/*physiology ; }, abstract = {Chagas disease can be transmitted to man by many different means, including contact with infected triatomine feces, blood transfusion, laboratory accidents, organ transplants, and congenital or oral routes. The latter mode has received considerable attention recently. In this assay, we evaluate the survival of Trypanosoma cruzi contaminating sugar cane used to prepare juice, as well as the viability and capacity for infection by the parasite after recovery. Thirty triatomines were contaminated with T. cruzi Y strain and 45 days later pieces of sugar cane were contaminated with the intestinal contents of the insects. The pieces were ground at different intervals after contamination (time=0, 1, 4, 6, 12 and 24 hours) and the juice extracted and analyzed. Different methods were used to show T. cruzi in the juice: direct analysis, hematocrit tube centrifugation and QBC, and experimental inoculation in 47 female BALB/c mice (five control mice and seven mice for each interval examined (five inoculated orally and two intraperitoneally). Positive results were found using the direct analysis and QBC methods for juice prepared up to 12 hours after initial contamination. However, by the centrifugation technique, positivity was found only up to four hours after contamination of the sugar cane. Inoculated animals showed parasitemia during a 14 day observation period, demonstrating the high survival rate of T. cruzi in sugar cane.}, }
@article {pmid17072371, year = {2006}, author = {Nagasaka, T and Goel, A and Matsubara, N and Tanaka, N}, title = {Detection of fecal DNA methylation for colorectal neoplasia: does it lead to an optimal screening test?.}, journal = {Acta medica Okayama}, volume = {60}, number = {5}, pages = {249-256}, doi = {10.18926/AMO/30741}, pmid = {17072371}, issn = {0386-300X}, mesh = {Colorectal Neoplasms/*diagnosis/*genetics ; DNA/*analysis/genetics ; *DNA Methylation ; Feces/*chemistry ; Humans ; Mass Screening/*methods/standards ; }, abstract = {Aberrant promoter methylation, an 'epigenetic' form of genomic instability that leads to transcriptional silencing of tumor suppressor genes, is increasingly being recognized as a crucial component in the evolution of human cancers. With our limited knowledge of the molecular basis and timing of the initiation of altered methylation events in the stepwise progression of cancers, the biggest challenge we currently face is to identify novel biomarkers and technologies for the timely screening of patients carrying such alterations. One such strategy would be to develop tests for the detection of fecal DNA methylation patterns that will improve the sensitivity of noninvasive screening tests for colorectal neoplasia, and moreover, will decrease both mortality and the incremental costs of treating colorectal cancers.}, }
@article {pmid17022014, year = {2006}, author = {Hetzer, FH and Bieler, A and Hahnloser, D and Löhlein, F and Clavien, PA and Demartines, N}, title = {Outcome and cost analysis of sacral nerve stimulation for faecal incontinence.}, journal = {The British journal of surgery}, volume = {93}, number = {11}, pages = {1411-1417}, doi = {10.1002/bjs.5491}, pmid = {17022014}, issn = {0007-1323}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cost-Benefit Analysis ; Electric Stimulation Therapy/*economics/methods ; Electrodes, Implanted ; Fecal Incontinence/economics/*therapy ; Female ; Humans ; *Lumbosacral Plexus ; Male ; Middle Aged ; Transcutaneous Electric Nerve Stimulation/economics/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Sacral nerve stimulation (SNS) may be successful in treating incapacitating faecal incontinence. The technique is expensive, and no cost analysis is currently available. The aim of this study was to assess clinical outcome and analyse cost-effectiveness.<br><br>METHODS: Thirty-six consecutive patients underwent a two-stage SNS procedure. Outcome parameters and real costs were assessed prospectively.<br><br>RESULTS: SNS was tested successfully in 33 of 36 patients, and 31 patients were stimulated permanently. In the first stage, eight of 36 patients reported minor complications (pain, infection or electrode dislocation), resulting in a cost of euro 4053 (range euro 2838-7273) per patient. For the second stage (permanent stimulation), eight of 33 patients had an infection, pain or loss of effectiveness, resulting in a cost of euro 11,292 (range euro 7406-20,274) per patient. Estimated costs for further follow-up were euro 997 per year. The 5-year cumulative cost for SNS was euro 22,150 per patient, compared with euro 33,996 for colostomy, euro 31,590 for dynamic graciloplasty and euro 3234 for conservative treatment.<br><br>CONCLUSION: SNS is a highly cost-effective treatment for faecal incontinence. Options for further reduction of SNS costs include strict patient selection, treatment in an outpatient setting and using cheaper devices.}, }
@article {pmid17015161, year = {2006}, author = {Matar, MJ and Tarrand, J and Raad, I and Rolston, KV}, title = {Colonization and infection with vancomycin-resistant Enterococcus among patients with cancer.}, journal = {American journal of infection control}, volume = {34}, number = {8}, pages = {534-536}, doi = {10.1016/j.ajic.2006.04.205}, pmid = {17015161}, issn = {0196-6553}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteremia/microbiology ; Enterococcus/*drug effects ; Feces/microbiology ; Gram-Positive Bacterial Infections/*microbiology ; Humans ; Leukemia/complications ; Lymphoma/complications ; Neoplasms/*complications ; Predictive Value of Tests ; Retrospective Studies ; Statistics as Topic ; Vancomycin/pharmacology ; *Vancomycin Resistance ; }, abstract = {Vancomycin-resistant enterococci (VRE) cause substantial morbidity and mortality in immune-suppressed patients. In a retrospective review, VRE fecal colonization was documented in 4.7% (99 of 2115) of patients screened, with 5.4% of patients with leukemia, 4.9% of hematopoietic stem cell transplantation recipients, and 2.2% of patients with lymphoma being colonized. Among the 99 patients with VRE colonization, 29 (29.29%) developed bacteremia, and there were 32 episodes of VRE infection at other sites. The rate of VRE bacteremia in solid tumor patients (0.12%) was significantly lower (P <or= .0001). VRE colonization had a negative predictive value of 99.9% and a positive predictive value of 29.3% for the development of VRE bacteremia and might help identify a high-risk subset of patients that might benefit from preemptive VRE therapy during episodes of neutropenic fever.}, }
@article {pmid16999758, year = {2006}, author = {Picardi, A and Tamburini, A and Caravita, T and De Angelis, C and Ballatore, G and Spagnoli, A and Malerba, C and Calugi, A and de Fabritiis, P and Amadori, S}, title = {Diagnosis of acute foetal distress does not preclude banking of umbilical cord blood units.}, journal = {Transfusion medicine (Oxford, England)}, volume = {16}, number = {5}, pages = {349-354}, doi = {10.1111/j.1365-3148.2006.00677.x}, pmid = {16999758}, issn = {0958-7578}, mesh = {Apgar Score ; Asphyxia Neonatorum ; Blood Donors ; *Blood Preservation/adverse effects/methods ; *Blood Specimen Collection/adverse effects/methods ; Contraindications ; Cryopreservation/methods ; Donor Selection/*methods/standards ; Female ; *Fetal Blood ; Fetal Distress/*blood ; Humans ; Infant, Newborn ; Meconium ; Pregnancy ; Pregnancy Outcome ; }, abstract = {Clinical diagnosis of acute foetal distress (AFD) is based on several parameters such as abnormal foetal heart rate (FHR) pattern and/or meconium liquid staining (MLS). Standards for cord blood (CB) banking indicate that AFD should be considered as exclusion criteria for CB collection, but precise guidelines on how to proceed with CB collection in the presence of AFD signs during labour are not available. We evaluated whether the presence of FHR abnormality and/or MLS during labour 1) reduced the CB collection activity; 2) were associated with the infant's acidaemia or asphyxia and 3) deteriorated the biological characteristics of CB units. Thirty-three units of CB were evaluated for biological parameters, gas values and newborn's Apgar score. The results were compared with a control group of 33 consecutive units previously banked. No differences were observed between the two groups and all but one newborn showed normal Apgar score and absence of metabolic acidaemia. The results showed that 1) AFD reduced the CB collection activity by 10% each year; 2) the majority of CB units collected in the presence of abnormal FHR and/or meconium have biological characteristics eligible for banking; 3) FHR alterations or meconium in the presence of normal gas analysis do not represent certain diagnosis of AFD.}, }
@article {pmid16951270, year = {2006}, author = {Kim, H and Kim, Y and Yoon, S and Lim, J and Kim, M and Lee, S and Kang, S and Lee, EJ and Kang, CS and Han, K}, title = {Rapid fecal cytokeratin-19 test and fecal occult blood test in screening for gastrointestinal diseases.}, journal = {Annals of clinical and laboratory science}, volume = {36}, number = {3}, pages = {294-298}, pmid = {16951270}, issn = {0091-7370}, mesh = {Adult ; Biomarkers, Tumor/*analysis ; Child ; Feces/*chemistry ; Gastrointestinal Diseases/*diagnosis ; Humans ; Keratin-19/*analysis ; Mass Screening/*methods ; *Occult Blood ; }, abstract = {To evaluate the screening power of the fecal cytokeratin-19 test (CK-19) and the fecal occult blood test (FOBT), we performed rapid fecal CK-19 and FOBT tests on 515 stool samples from patients with various GI diseases and 814 stool samples from control patients. The rapid fecal CK-19 test (developed by DiNonA Research Institute, Seoul, Korea) is based on gold immunochromatography and has a sensitivity of 1 ng/ml. The positive rate of the FOBT was 2.1% in controls, 14.0% in GI cancer patients, 3.5% in GI inflammation patients, 11.7% in bone marrow transplant (BMT) patients, and 6.0% in childhood diarrhea patients. Except for the GI inflammation patients, the patients' positive rates for FOBT were all higher than the controls (p <0.05). The positive rate of the fecal CK-19 test was 8.2% in controls, 42.1% in GI cancer patients, 66.0% in GI inflammation patients, 84.8% in BMT patients, and 19.9% in childhood diarrhea patients. In all of the patient groups, positive rates for the CK-19 test were higher than in the controls (p <0.05). The fecal CK-19 test was more frequently positive (42.1%) in GI cancer patients than the FOBT; if both tests were used, the sensitivity was 49.1%. The fecal CK-19 test (but not the FOBT) gave a higher positive rate in GI inflammation patients than the controls, suggesting that the CK-19 test could serve as a screening test for GI inflammation. The highest positive rate of the fecal CK-19 test was found in the BMT group, indicating that significant GI epithelial desquamation had occurred. Although the positive rate of the fecal CK-19 test in childhood diarrhea patients was higher than in the controls, it was much lower than in adults with GI inflammatory disease. Evidently, children with GI inflammation do not desquamate as much intestinal epithelium as adult patients with GI inflammation. This study shows that the rapid fecal GK-19 test, used in conjunction with the FOBT, may be a valuable screening technique for GI diseases and can assist physicians in the differential diagnosis of GI diseases.}, }
@article {pmid16923193, year = {2006}, author = {Freitas, MC and Pacheco-Silva, A and Barbosa, D and Silbert, S and Sader, H and Sesso, R and Camargo, LF}, title = {Prevalence of vancomycin-resistant Enterococcus fecal colonization among kidney transplant patients.}, journal = {BMC infectious diseases}, volume = {6}, number = {}, pages = {133}, pmid = {16923193}, issn = {1471-2334}, mesh = {Adult ; Enterococcus/*growth &amp; development ; Feces/microbiology ; Female ; Gram-Positive Bacterial Infections/*epidemiology/microbiology ; Humans ; *Kidney Transplantation ; Male ; Middle Aged ; Prevalence ; *Vancomycin Resistance ; }, abstract = {BACKGROUND: End stage renal disease patients are at risk of Vancomycin-Resistant Enterococcus (VRE) infections. The first reports of VRE isolation were from hemodialysis patients. However, to date, VRE fecal colonization rates as well as associated risk factors in kidney transplant patients have not yet been established in prospective studies.<br><br>METHODS: We collected one or two stool samples from 280 kidney transplant patients and analysed the prevalence of VRE and its associated risk factors. Patients were evaluated according to the post-transplant period: group 1, less than 30 days after transplantation (102 patients), group 2, one to 6 months after transplantation (73 patients) and group 3, more than 6 months after transplantation (105 patients).<br><br>RESULTS: The overall prevalence rate of fecal VRE colonization was 13.6% (38/280), respectively 13.7% for Group 1, 15.1% for group 2 and 12.4% for group 3. E. faecium and E. faecalis comprised 50% of all VRE isolates. No immunologic variables were clearly correlated with VRE colonization and no infections related to VRE colonization were reported.<br><br>CONCLUSION: Fecal VRE colonization rates in kidney transplant patients were as high as those reported for other high-risk groups, such as critical care and hemodialysis patients. This high rate of VRE colonization observed in kidney transplant recipients may have clinical relevance in infectious complications.}, }
@article {pmid16919115, year = {2006}, author = {Hübner, M and Hetzer, F and Weishaupt, D and Hahnloser, D and Clavien, PA and Demartines, N}, title = {A prospective comparison between clinical outcome and open-configuration magnetic resonance defecography findings before and after surgery for symptomatic rectocele.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {8}, number = {7}, pages = {605-611}, doi = {10.1111/j.1463-1318.2006.01026.x}, pmid = {16919115}, issn = {1462-8910}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anal Canal/diagnostic imaging/physiopathology ; Defecography ; Digestive System Surgical Procedures/methods ; Electromyography ; Female ; Humans ; Middle Aged ; Postoperative Complications/diagnostic imaging/*physiopathology ; Preoperative Care/methods ; Prospective Studies ; Quality of Life ; Rectocele/*diagnostic imaging/physiopathology/*surgery ; }, abstract = {BACKGROUND: The correlation between clinical symptoms and anatomical findings by conventional imaging is poor in patients with rectoceles. The aim of this prospective study was to assess and to correlate symptomatic changes after anterior levatorplasty with morphologic changes visualized by magnetic resonance defecography (MRD).<br><br>METHOD: Fourteen women with a median age of 57 (range 37-83) accepted to participate. Seven of 14 had previous hysterectomy. Patients underwent MRD before surgery and again 6 months postsurgery. Pre- and postoperative symptoms and quality of life (QoL) (Eypasch) were assessed. Faecal and urinary incontinence were graded (Wexner- / Hanley-score).<br><br>RESULTS: The median Eypasch-score improved from 90 (range 38-106) to 106 (range 29-133) after surgery (P = 0.016). Similarly, the Wexner-score ameliorated from 8 (range 0-20) to 4.5 (range 0-18; P = 0.02). Seven patients described new dyspareunia postoperatively. The median follow up was 16.5 months (range 9-45). The median rectocele size decreased from 37 mm (range 30-48) preoperatively to 12 mm (range 0-42) postoperatively (P = 0.004). Furthermore, enteroceles were corrected and pelvic floor descent was significantly reduced after surgery. Only the clinical symptom of incomplete evacuation strongly correlated with the respective radiological finding of contrast dye trapping (Rho = 0.822; P = 0.001).<br><br>CONCLUSION: Anterior levatorplasty improved QoL in patients with symptomatic rectocele. Postsurgical correction of rectocele is accurately documented by MRD. Only moderate correlation between morphologic and clinical improvements was observed.}, }
@article {pmid16896900, year = {2006}, author = {Ruthmann, O and Fischer, A and Hopt, UT and Schrag, HJ}, title = {[Dynamic graciloplasty vs artificial bowel sphincter in the management of severe fecal incontinence].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {77}, number = {10}, pages = {926-938}, pmid = {16896900}, issn = {0009-4722}, mesh = {Anal Canal/*surgery ; Electric Stimulation Therapy ; Equipment Failure Analysis ; Evidence-Based Medicine ; Fecal Incontinence/etiology/*surgery ; Follow-Up Studies ; Humans ; Muscle, Skeletal/*transplantation ; Outcome and Process Assessment, Health Care ; Postoperative Complications/etiology ; *Prostheses and Implants ; Prosthesis Design ; }, abstract = {Dynamic graciloplasty (DGP) and the Acticon Neosphincter (artificial bowel sphincter, ABS) are well-established therapeutic instruments in patients with severe fecal incontinence. However, the success rates in the literature must be interpreted with caution. The report presented here presents firstly a critical analysis of 1510 patients in 52 studies (29 DGP vs 23 ABS). The evidence of these studies was assessed using the Oxford EBM criteria. All data were statistically analysed. Up to 94% of the studies analysed show EBM levels of only >3b. Both procedures show significant improvements in postoperative continence scores (p<0.001) and a significant advantage of ABS over DGP. Nevertheless, they are associated with a high incidence of morbidity in the long term (infection rate ABS vs DGP 21.74% vs 35.1%, revision rate ABS vs DGP 37.53% vs 40.64%, and ABS explantation rates of 30%). Presently no therapeutic recommendation can be expressed based on the few data available. Furthermore, therapy should be performed in specialized centers and patients should be given a realistic picture of the critical outcome of both surgical techniques.}, }
@article {pmid16874295, year = {2006}, author = {, }, title = {Chagas disease after organ transplantation--Los Angeles, California, 2006.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {55}, number = {29}, pages = {798-800}, pmid = {16874295}, issn = {1545-861X}, mesh = {Aged ; Animals ; Chagas Disease/*transmission ; Fluorescent Antibody Technique ; Heart Transplantation/*adverse effects ; Humans ; Los Angeles ; Male ; Middle Aged ; Radioimmunoprecipitation Assay ; *Tissue Donors ; Trypanosoma cruzi/*isolation &amp; purification ; }, abstract = {Chagas disease is an infection caused by the parasite Trypanosoma cruzi. Reduviids (i.e., "kissing bugs") transmit the parasite through infected feces. T. cruzi also can be transmitted congenitally and through blood transfusion or organ transplantation. The infection is lifelong if left untreated; the majority of infected persons are asymptomatic, and their disease remains undiagnosed. Although routine serologic testing of organ and blood donors is performed in areas of Latin America where Chagas disease is endemic, no T. cruzi screening test is licensed in the United States. However, seroprevalence studies using research tests have documented the presence of T. cruzi antibodies in U.S. blood and organ donor populations. This report describes two cases of acute Chagas disease in heart transplant recipients reported by two Los Angeles County hospitals in February 2006. In the United States, one previous report documented T. cruzi transmission through solid organ transplantation, in which three organ recipients were infected.}, }
@article {pmid16850020, year = {2006}, author = {Hoppe, B and Beck, B and Gatter, N and von Unruh, G and Tischer, A and Hesse, A and Laube, N and Kaul, P and Sidhu, H}, title = {Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1.}, journal = {Kidney international}, volume = {70}, number = {7}, pages = {1305-1311}, doi = {10.1038/sj.ki.5001707}, pmid = {16850020}, issn = {0085-2538}, mesh = {Administration, Oral ; Adolescent ; Adult ; Capsules ; Child ; Child, Preschool ; Chromatography, Gas ; Creatinine/urine ; Feces/microbiology ; Female ; Flame Ionization ; Follow-Up Studies ; Humans ; Hyperoxaluria, Primary/blood/classification/complications/*therapy/urine ; Kidney/physiology ; Kidney Diseases/complications/diagnostic imaging ; Kidney Failure, Chronic/complications ; Kidney Function Tests ; Kidney Transplantation ; Male ; Middle Aged ; Oxalates/blood/urine ; *Oxalobacter formigenes/isolation &amp; purification ; Time Factors ; Treatment Outcome ; Ultrasonography ; }, abstract = {Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC-2) or as enteric-coated capsules (IxOC-3). Nine patients (five with normal renal function, one after liver-kidney transplantation, and three with renal failure) completed the IxOC-2 study. Seven patients (six with normal renal function and one after liver-kidney transplantation) completed the IxOC-3 study. Urinary oxalate or plasma oxalate in renal failure was determined at baseline, weekly during treatment and for a 2-week follow-up. The patients who showed >20% reduction both at the end of weeks 3 and 4 were considered as responders. Under IxOC-2, three out of five patients with normal renal function showed a 22-48% reduction of urinary oxalate. In addition, two renal failure patients experienced a significant reduction in plasma oxalate and amelioration of clinical symptoms. Under IxOC-3 treatment, four out of six patients with normal renal function responded with a reduction of urinary oxalate ranging from 38.5 to 92%. Although all subjects under IxOC-2 and 4 patients under IxOC-3 showed detectable levels of O. formigenes in stool during treatment, fecal recovery dropped directly at follow up, indicating only transient gastrointestinal-tract colonization. The preliminary data indicate that O. formigenes is safe, leads to a significant reduction of either urinary or plasma oxalate, and is a potential new treatment option for primary hyperoxaluria.}, }
@article {pmid16848078, year = {2006}, author = {Brundage, SC and Fitzpatrick, AN}, title = {Hepatitis A.}, journal = {American family physician}, volume = {73}, number = {12}, pages = {2162-2168}, pmid = {16848078}, issn = {0002-838X}, mesh = {Diagnosis, Differential ; Hand Disinfection ; Hepatitis A/complications/*diagnosis/epidemiology/*therapy ; Hepatitis A Vaccines/administration &amp; dosage ; Hepatovirus/immunology ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Liver Failure, Acute/virology ; Refuse Disposal ; Vaccination/standards ; }, abstract = {The introduction of hepatitis A vaccines in 1995 led to a drop in the number of reported cases of hepatitis A and a shift to a higher percentage of cases occurring in older age groups. The hepatitis A virus survives for extended periods in the environment. Transmission primarily is fecal-oral, although there have been rare instances of transmission through blood products. The virus appears sporadically and is spread by close personal contact, with occasional food-borne outbreaks. Older persons infected by the virus usually develop a symptomatic infection with abrupt onset, fever, and jaundice lasting two months. Children usually have an asymptomatic infection and rarely develop jaundice. Laboratory diagnosis is made by detection of antihepatitis A virus immunoglobulin M in serum. Ten to 20 percent of symptomatic patients experience a prolonged or relapsing course of illness, but chronic infection has not been reported. Fulminant infection occurs in less than 1 percent of patients and can result in emergent liver transplant or death. Prevention starts with thorough handwashing and careful food handling. Prompt disease reporting, the identification of exposed persons, and expeditious administration of immune globulin prevent secondary transmission of the disease. Physicians should consider routine vaccination of children 12 to 23 months of age based on recommendations from the Centers for Disease Control and Prevention. Vaccination for children two years or older and adults should be included in routine preventive care for those at increased risk of contracting the disease (e.g., travelers to certain countries, men who have sex with men, drug abusers, recipients of clotting factor replacement) and for persons with chronic liver disease.}, }
@article {pmid16841591, year = {2006}, author = {Rendering, H and Zijlstra, JG and van Son, WJ and de Maar, EF and Manson, WL and van der Werf, TS}, title = {[Intestinal perforation caused by tuberculosis in a kidney transplant patient who was extensively evaluated for tuberculosis prior to transplant].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {150}, number = {25}, pages = {1407-1412}, pmid = {16841591}, issn = {0028-2162}, mesh = {Antitubercular Agents/therapeutic use ; Fatal Outcome ; Humans ; Immunocompromised Host ; Intestinal Perforation/*diagnosis/etiology ; Kidney Transplantation/*immunology ; Male ; Middle Aged ; Mycobacterium tuberculosis/isolation &amp; purification ; Peritonitis/*diagnosis/etiology ; Tuberculosis/complications/*diagnosis ; }, abstract = {A 47-year-old man from Armenia presented at the emergency department with abdominal pain. He had had a kidney transplant 2 years earlier for renal failure caused by amyloidosis that was secondary to familial Mediterranean fever. He was also known to have chronic hepatitis B with persistent viraemia. He had not received any prophylactic anti-tuberculosis treatment due to impaired liver function, but an extensive work-up was performed prior to transplant, including chest radiography, a Mantoux tuberculin skin test and cultures from 3 consecutive fasting gastric lavage samples, which were all negative for active or latent tuberculosis infection. The patient had presented at the emergency department repeatedly with abdominal pain that was attributed to the familial Mediterranean fever. During his last visit his complaints were accompanied by vomiting, coughing, night sweats and weight loss. He was diagnosed with an intestinal perforation with faecal peritonitis and underwent several laparotomies to treat the faecal peritonitis. Histopathological examination of resected bowel tissue revealed granulomatous inflammation, and acid-fast bacilli were seen with appropriate staining. Later, cultures appeared to be positive for normally sensitive Mycobacterium tuberculosis. The patient died as a result of the disseminated tuberculosis. In immunocompromised patients, tuberculosis often has an atypical course and an increased chance of dissemination that may be difficult to recognize.}, }
@article {pmid16801366, year = {2006}, author = {Hetzer, FH and Andreisek, G and Tsagari, C and Sahrbacher, U and Weishaupt, D}, title = {MR defecography in patients with fecal incontinence: imaging findings and their effect on surgical management.}, journal = {Radiology}, volume = {240}, number = {2}, pages = {449-457}, doi = {10.1148/radiol.2401050648}, pmid = {16801366}, issn = {0033-8419}, mesh = {Defecation/*physiology ; Fecal Incontinence/*physiopathology/surgery ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Observer Variation ; Prospective Studies ; Rectal Prolapse/diagnosis ; Rectocele/diagnosis ; Retrospective Studies ; }, abstract = {PURPOSE: To retrospectively evaluate magnetic resonance (MR) defecography findings in patients with fecal incontinence who were evaluated for surgical treatment and to assess the influence of MR defecography on surgical therapy.<br><br>MATERIALS AND METHODS: Institutional review board approval was obtained. Informed consent was waived; however, written informed consent for imaging was obtained. Fifty patients (44 women, six men; mean age, 61 years) with fecal incontinence were placed in a sitting position and underwent MR defecography performed with an open-configuration MR system. Midsagittal T1-weighted MR images were obtained at rest, at maximal contraction of the sphincter, and at defecation. Images were prospectively and retrospectively reviewed by two independent observers for a variety of findings. Interobserver agreement was analyzed by calculating kappa statistics. Prospective interpretation of MR defecography findings was used to influence surgical therapy, and retrospective interpretation was used for concomitant pelvic floor disorders.<br><br>RESULTS: MR defecography revealed rectal descent of more than 6 cm (relative to the pubococcygeal line) in 47 (94%) of 50 patients. A bladder descent of more than 3 cm was present in 20 (40%) of 50 patients, and a vaginal vault descent of more than 3 cm was present in 19 (43%) of 44 women. Moreover, 17 (34%) anterior proctoceles, 16 (32%) enteroceles, and 10 (20%) rectal prolapses were noted. Interobserver agreement was good to excellent (kappa = 0.6-0.91) for image analysis results. MR defecography findings led to changes in the surgical approach in 22 (67%) of 33 patients who underwent surgery.<br><br>CONCLUSION: MR defecography may demonstrate a variety of abnormal findings in patients who are considered candidates for surgical therapy for fecal incontinence, and the findings may influence the surgical treatment that is subsequently chosen.<br><br>SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2402050648/DC1}, }
@article {pmid16782548, year = {2006}, author = {Kjellev, S and Lundsgaard, D and Poulsen, SS and Markholst, H}, title = {Reconstitution of Scid mice with CD4+CD25- T cells leads to rapid colitis: an improved model for pharmacologic testing.}, journal = {International immunopharmacology}, volume = {6}, number = {8}, pages = {1341-1354}, doi = {10.1016/j.intimp.2006.04.017}, pmid = {16782548}, issn = {1567-5769}, mesh = {Adoptive Transfer/adverse effects/methods ; Animals ; CD11c Antigen/analysis ; CD4 Antigens/analysis ; CD4-Positive T-Lymphocytes/cytology/*immunology/transplantation ; Colitis/etiology/*immunology/pathology ; Colon/metabolism/pathology ; Cytokines/blood ; Disease Models, Animal ; Epithelium/immunology/pathology ; Female ; Goblet Cells/metabolism ; Immunohistochemistry ; In Situ Hybridization ; Inflammation/etiology/immunology/pathology ; Inflammation Mediators/metabolism ; Intestinal Mucosa/immunology/pathology ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Occult Blood ; Peptides/genetics/metabolism ; Receptors, Interleukin-2/analysis ; Trefoil Factor-2 ; }, abstract = {Improved experimental colitis models are needed for evaluation of treatment strategies for IBD. Most current models either lack resemblance to IBD, are complicated to establish, or the colitis occurs slowly and inconsistently. Our aim was to characterize the course of colitis in C.B-17 Scid mice reconstituted with syngeneic CD25-depleted CD4+ cells, including the identification of useful biomarkers, and assessment of the similarities to IBD with focus on the relationship between colonic epithelial proliferation and inflammatory parameters. Groups of reconstituted and un-reconstituted mice were sacrificed weekly from week 1 to 4. Clinical signs of colitis occurred approximately 2 weeks after reconstitution. Disease onset and severity based on histopathology correlated well with the colonic weight:length ratio, fecal consistency score, presence of occult blood in feces, and fecal IL-1beta content. Loss in body weight was not apparent until colitis was well established and exhibited lower coefficient of correlation to the histologic score. Early colonic histopathology was dominated by epithelial hyperproliferation, loss of mucus and mild lymphoid infiltration. Epithelial hyperproliferation was paralleled by increased fecal soluble tumor necrosis factor receptor II content. Cytokines in colonic tissue homogenates exhibited a Th1-like profile. We conclude that adoptive transfer of CD4+CD25- T cells results in colitis resembling IBD with a rapid onset and limited variability between individuals. Purification of CD4+CD25- T cells is a simple procedure, and does not require flow-cytometric sorting. Fecal consistency score and colonic weight:length ratio are readily measurable and consistent disease parameters. This model is thus highly suitable for pharmacological testing of intervention strategies.}, }
@article {pmid16773288, year = {2006}, author = {Hetzer, FH and Hahnloser, D and Clavien, PA and Demartines, N}, title = {Video-assisted sacral nerve stimulation.}, journal = {Techniques in coloproctology}, volume = {10}, number = {2}, pages = {121-3; discussion 123-4}, doi = {10.1007/s10151-006-0264-3}, pmid = {16773288}, issn = {1123-6337}, mesh = {Aged ; Constipation/*therapy ; Electric Stimulation Therapy/*instrumentation ; Electrodes, Implanted ; Fecal Incontinence/*therapy ; Female ; Follow-Up Studies ; Humans ; *Lumbosacral Plexus ; Middle Aged ; Prosthesis Implantation/*methods ; *Video-Assisted Surgery ; }, abstract = {BACKGROUND: Sacral nerve simulation (SNS) is an accepted therapy for patients with urinary or bowel dysfunction. However, infection rates are as high as 20% and can result in removal of the expensive device. We present a new video-assisted technique minimizing the risk of infection.<br><br>METHODS: Between April and July 2005, six consecutive women of median age 68 years (range, 60-74), with faecal incontinence (4 patients) and idiopathic constipation (2 patients) underwent video-assisted electrode implantation for SNS. The motor response of the pelvic floor during percutaneous nerve evaluation and implantation of the permanent lead was monitored by a video optic (same as that normally used for laparoscopic or endoscopic procedures) placed between the legs of the patients. The video optic and the perianal area were completely covered with drapes, separating them from the operating field.<br><br>RESULTS: All but one screening was successful, and no wound infections at the electrode or at the pocket of the stimulator were noted (mean postoperative follow-up, 8 weeks).<br><br>CONCLUSIONS: With the use of a video optic, the anus and the implantation site can be completely separated and contamination during the operation becomes unlikely. Furthermore, the response of the pelvic floor to the stimulation is better visualized. We routinely recommend the use of video equipment for SNS electrode implantation.}, }
@article {pmid16753375, year = {2006}, author = {Dall'Era, MA and Hampson, NB and Hsi, RA and Madsen, B and Corman, JM}, title = {Hyperbaric oxygen therapy for radiation induced proctopathy in men treated for prostate cancer.}, journal = {The Journal of urology}, volume = {176}, number = {1}, pages = {87-90}, doi = {10.1016/S0022-5347(06)00491-5}, pmid = {16753375}, issn = {0022-5347}, mesh = {Aged ; Aged, 80 and over ; Brachytherapy/adverse effects ; Humans ; *Hyperbaric Oxygenation/adverse effects ; Male ; Middle Aged ; Proctitis/etiology/*therapy ; Prostatic Neoplasms/*radiotherapy ; Radiation Injuries/etiology/*therapy ; Treatment Outcome ; }, abstract = {PURPOSE: Radiation proctitis is a common complication following external beam radiation therapy and brachytherapy for prostate cancer. While 95% percent of radiation induced proctitis is temporary and self-limiting, up to 5% of patients experience toxicities that are refractory to conservative management. Hyperbaric oxygen has a well-defined role in treating chronic wounds, osteomyelitis, hemorrhagic cystitis and necrotizing fasciitis. We reviewed our experience with hyperbaric oxygen therapy for radiation induced proctitis in patients undergoing radiation treatment for prostate cancer.<br><br>MATERIALS AND METHODS: From October 1998 to December 2003, 27 patients with radiation induced proctitis secondary to brachytherapy (4), external beam radiation therapy (16) or combined modality (7) for prostate cancer were treated with hyperbaric oxygen therapy at Virginia Mason Medical Center in Seattle, Washington. In all patients primary medical or endoscopic management had failed. Patients received 100% oxygen in a multiplace hyperbaric chamber at a pressure of 2.4 atmospheres absolute for 90 minutes 5 to 7 days weekly for an average of 36 sessions (range 29 to 60). Data were collected from a retrospective review of medical records following approval by the Institutional Review Board at Virginia Mason Medical Center.<br><br>RESULTS: All 27 men completed the planned course of therapy. Of patients with bleeding 48% showed complete resolution after therapy, while 28% reported significantly fewer bleeding episodes. Of patients 50% noted complete resolution of fecal urgency. Six of the 8 patients (75%) with pain noticed some improvement after therapy, although no patients reported complete resolution of rectal pain. Of patients with rectal ulceration 21% showed complete resolution of the ulcer on posttreatment endoscopy, while 29% showed evidence of improvement. Six patients (43%) had no change or worsening of rectal ulcers. Overall 67% of patients had a partial to good response, while 33% showed no response or disease progression.<br><br>CONCLUSIONS: This series of patients showed a good overall response rate to hyperbaric oxygen for radiation induced proctopathy after other attempts at management had failed. Hyperbaric oxygen is generally well tolerated and it remains an important treatment option for managing this common and difficult disease.}, }
@article {pmid16752191, year = {2006}, author = {Zmora, O and Tulchinsky, H and Gur, E and Goldman, G and Klausner, JM and Rabau, M}, title = {Gracilis muscle transposition for fistulas between the rectum and urethra or vagina.}, journal = {Diseases of the colon and rectum}, volume = {49}, number = {9}, pages = {1316-1321}, doi = {10.1007/s10350-006-0585-3}, pmid = {16752191}, issn = {0012-3706}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Postoperative Complications ; Rectal Fistula/*surgery ; Rectovaginal Fistula/*surgery ; *Surgical Flaps ; Urethral Diseases/*surgery ; Urinary Fistula/*surgery ; }, abstract = {PURPOSE: This study was designed to assess the efficacy of gracilis muscle transposition in repairing rectovaginal and rectourethral fistulas.<br><br>METHODS: Data were retrieved from a retrospective chart review of patients who underwent gracilis muscle transposition for fistulas between the rectum and urethra/vagina. All patients had fecal diversion as a preliminary or concurrent step to fistula repair. Follow-up data were gathered from outpatient clinic visits. Success was defined as a healed fistula after stoma closure.<br><br>RESULTS: Six females and three males, aged 30 to 64 years, underwent gracilis muscle transpositions from 1999 to 2005. One pouch-vaginal, three rectourethral, and five rectovaginal fistulas were repaired. The etiologies were Crohn's disease (n = 2), iatrogenic injury to the rectum during radical prostatectomy (n = 2), previous pelvic irradiation for rectal cancer (n = 2) or for cervical cancer (n = 1), recurrent perianal abscesses with fistulas (n = 1), and obstetric tear (n = 1). Seven patients underwent previous medical and surgical repair attempts. There were no intraoperative complications. Postoperative complications included perineal wound infection (n = 1) and at the colostomy closure (n = 2). There were no long-term sequelae. At a median follow-up period of 14 (range, 1-66) months since stoma closure, the fistula healed in seven patients. One patient refused ileostomy closure. One patient with severe Crohn's proctitis has a persistent rectovaginal fistula.<br><br>CONCLUSIONS: Gracilis muscle transposition is a viable option for repairing fistulas between the urethra, vagina, and the rectum, especially after failed perineal or transanal repairs. It is associated with low morbidity and a good success rate. Underlying Crohn's disease and previous radiation are associated with poor prognosis.}, }
@article {pmid16736617, year = {2006}, author = {Wang, XC and Qiao, Q and Liu, ZF and Zhao, R and Zhao, YM and Wang, CF and Zeng, A and Qi, KM}, title = {[The application of pedicled anterolateral thigh fasciocutaneous flaps for reconstruction of perineal and inguinal defects].}, journal = {Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery}, volume = {22}, number = {2}, pages = {127-129}, pmid = {16736617}, issn = {1009-4598}, mesh = {Adult ; Female ; Femur/surgery ; Groin/*surgery ; Humans ; Middle Aged ; Perineum/*surgery ; Plastic Surgery Procedures/methods ; *Skin Transplantation ; *Surgical Flaps ; Wound Healing ; }, abstract = {OBJECTIVE: To evaluate a method for the reconstruction of defects of perineum and groin with pedicled anterolateral thigh fasciocutaneous flaps.<br><br>METHODS: From July 2003 to February 2005, 12 pedicled anterolateral thigh fasciocutaneous flap based on the perforators of lateral circumflex femoral artery had been designed and transferred to the defects of perineum and groin.<br><br>RESULTS: Anterolateral thigh fasciocutaneous island flaps were performed in twelve patients. The size of the transferred flap ranged from 8 cm x 11 cm to 18 cm x 20 cm. Only one patient developed superficial cutaneous necrosis in the posterior aspect of the flap because of fecal contamination and infection. The wounds healed secondarily.<br><br>CONCLUSIONS: Despite variable vascular anatomy and technical difficulties in elevating the anterolateral thigh flap, the anterolateral thigh flap is a good choice for perineum and groin reconstruction.}, }
@article {pmid16644900, year = {2006}, author = {Gustafson, DL and Bradshaw-Pierce, EL and Merz, AL and Zirrolli, JA}, title = {Tissue distribution and metabolism of the tyrosine kinase inhibitor ZD6474 (Zactima) in tumor-bearing nude mice following oral dosing.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {318}, number = {2}, pages = {872-880}, doi = {10.1124/jpet.106.102376}, pmid = {16644900}, issn = {0022-3565}, support = {CA101988/CA/NCI NIH HHS/United States ; }, mesh = {Angiogenesis Inhibitors/*pharmacokinetics ; Animals ; Antineoplastic Agents/*pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; Dose-Response Relationship, Drug ; Drug Delivery Systems ; Estradiol/administration &amp; dosage/pharmacology ; Feces/chemistry ; Female ; Liver/drug effects/metabolism ; Mass Spectrometry ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Piperidines/*pharmacokinetics ; Protein-Tyrosine Kinases/*antagonists &amp; inhibitors ; Quinazolines/*pharmacokinetics ; Reproducibility of Results ; Tissue Distribution ; Transplantation, Heterologous ; }, abstract = {ZD6474 [N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-quinazolin-4-amine; Zactima] is a tyrosine kinase inhibitor with antiangiogenic and antitumor activity currently undergoing human trials for cancer treatment. Pharmacokinetic studies in animal models are an important component in the clinical development of this agent to relate preclinical studies to patient treatment. In the studies presented here, the pharmacokinetics of ZD6474 was determined in plasma and tissues of MCF-7 tumor-bearing nude mice following single p.o. doses at 10, 25, and 50 mg/kg. Plasma area under the curve and Cmax were linear, increasing proportionally with dose. Tissue analysis showed that ZD6474 is extensively distributed to tissues, with liver and lung accumulating concentrations of 212 microg/g (approximately 450 microM) and 161 microg/g (approximately 340 microM), respectively. Tumor levels ranged from 27 to 71 microg/g at Cmax levels across the three dose ranges, and ZD6474 was distributed to all of the tissues in a dose-dependent manner. Analysis of putative ZD6474 metabolites in feces found four, with the N-demethyl-piperidinyl-ZD6474 metabolite being the most prominent but still accounting for less than 2% of the total amount of ZD6474 present. The lack of significant metabolism of ZD6474 is consistent with the relatively long half-life in mice (approximately 30 h), as well as that seen in humans (approximately 120 h), and the primary method of drug elimination appears to be unchanged in the feces (approximately 25%). The incorporation of an empirical approach to dosing in mouse models of cancer in preclinical studies may allow for better prediction of clinical efficacy for ZD6474 alone and in combination with other therapeutic modalities based on equivalent drug exposure.}, }
@article {pmid16623822, year = {2006}, author = {Rosario, RF and Kimbrough, RC and Van Buren, DH and Laski, ME}, title = {Fatal adenovirus serotype-5 in a deceased-donor renal transplant recipient.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {8}, number = {1}, pages = {54-57}, doi = {10.1111/j.1399-3062.2006.00137.x}, pmid = {16623822}, issn = {1398-2273}, mesh = {Adenoviridae/*isolation &amp; purification ; Adenovirus Infections, Human/*diagnosis/mortality ; Colitis/virology ; Fatal Outcome ; Feces/virology ; Fluorescent Antibody Technique, Direct/methods ; Humans ; *Immunocompromised Host ; Immunosuppressive Agents/adverse effects ; *Kidney Transplantation ; Male ; Middle Aged ; Viremia ; }, }
@article {pmid16617288, year = {2006}, author = {, }, title = {Survey of lymphocytic choriomeningitis virus diagnosis and testing--Connecticut, 2005.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {55}, number = {14}, pages = {398-399}, pmid = {16617288}, issn = {1545-861X}, mesh = {Clinical Laboratory Techniques/statistics &amp; numerical data ; Connecticut/epidemiology ; Data Collection ; Humans ; Lymphocytic Choriomeningitis/*diagnosis/*epidemiology ; Lymphocytic choriomeningitis virus/*isolation &amp; purification ; }, abstract = {Lymphocytic choriomeningitis virus (LCMV) is a rodent borne virus that can be transmitted to humans through exposure to rodent urine, feces, saliva, or blood. LCMV infection is often asymptomatic or mild but can cause aseptic meningitis, encephalitis, life-threatening infections in immunosuppressed persons, and severe congenital defects . In May 2005, LCMV was implicated in the deaths of three organ transplant recipients who had received organs from a common donor who had likely been infected from a pet rodent. In August 2005, the Connecticut Department of Public Health conducted surveys of hospital laboratories and infectious disease (ID) physicians in Connecticut to determine recent incidence of confirmed LCMV infection, the level of awareness of LCMV, and the frequency of LCMV testing. This report summarizes the results of those surveys, which indicate that awareness of LCMV is high among ID physicians; however, testing for LCMV is infrequent, and ID physicians might not be aware of the need to consider LCMV among the most susceptible populations even when a history of rodent contact is not initially evident. In part because of these findings, LCMV infection is now a physician- and laboratory-reportable disease in Connecticut. More systematic efforts are needed to determine the frequency of LCMV infection and to monitor for pet rodent infection.}, }
@article {pmid16608391, year = {2006}, author = {Stelzner, M and Chen, DC}, title = {To make a new intestinal mucosa.}, journal = {Rejuvenation research}, volume = {9}, number = {1}, pages = {20-25}, doi = {10.1089/rej.2006.9.20}, pmid = {16608391}, issn = {1549-1684}, mesh = {Animals ; Ileum/cytology/surgery ; Intestinal Mucosa/*cytology/*transplantation ; Jejunum/cytology/surgery ; Malabsorption Syndromes/surgery ; Rats ; Stem Cells/cytology ; *Tissue Engineering ; }, abstract = {A number of clinical conditions are caused by disorders affecting the mucosal lining of the gastrointestinal tract. Some patients suffer from a loss of mucosal surface area due to congenital defects or due to surgical resections ("short bowel syndrome"). Other patients have inborn or acquired defects of certain mucosal functions (e.g., glucose-galactose malabsorption, bile acid malabsorption). Many patients with these mucosal disorders could be more effectively treated if healthy mucosa were available in larger quantities as a replacement or functional supplement. We therefore developed methods to transplant mucosal stem cells from one part of the intestine to another and to make bioengineered intestinal mucosa. We generated an animal model of bile acid malabsorption using rats that underwent resection of the distal 25% of their small intestine (ileum). This resulted in significant losses of bile acids with the fecal excretions in these animals. We subsequently harvested ileal stem cell clusters from neonatal donors, removed the mucosa from a segment of proximal intestine (jejunum), and implanted the stem cell clusters into the debrided segment of jejunum. After four weeks, the animals had developed a functional "neomucosa." We inserted the "neo-ileal" segment into continuity as a substitute ileum. Postoperative measurements of fecal bile acid excretion showed that we were able to reverse the malabsorption syndrome in this model. This was the first reported neo-mucosa-based treatment of a malabsorption syndrome in vivo. We subsequently studied different biodegradable PGA and PLLA scaffoldings to generate bioengineered intestinal mucosa. We implanted these materials into omentum of rats and were able to identify a PGA/PLLA hybrid material on which engraftment rates of 36% of the available surface area could be achieved. Most recently, we developed a novel technique that permits direct observation of cell-biomaterial interactions after implantation into omentum or intestine in vivo. This method will help to optimize engraftment conditions for stem cell clusters on biomaterials.}, }
@article {pmid16607790, year = {2005}, author = {Tăranu, T and Covic, A and Târcoveanu, E and Florea, L}, title = {[Anatomical and clinical evaluation regarding the removal of the peritoneal dialysis catheter].}, journal = {Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi}, volume = {109}, number = {2}, pages = {300-304}, pmid = {16607790}, issn = {0048-7848}, mesh = {Catheters, Indwelling/*adverse effects ; *Device Removal ; Evaluation Studies as Topic ; Female ; Humans ; Kidney Failure, Chronic/mortality/*pathology/therapy ; Male ; Peritoneal Dialysis, Continuous Ambulatory/*adverse effects/instrumentation/mortality ; Peritonitis/etiology/prevention &amp; control ; Retrospective Studies ; Risk Factors ; Romania/epidemiology ; Survival Analysis ; }, abstract = {To describe CAPD technique survival and causes for catheter removal. The study included 320 end stage renal disease (ESRD) patients, initiated on CAPD between 1995-2003. Definitive catheter removal was required in 44 cases (15.1%), 11 of these (3.79%) receiving renal transplant. Causes for catheter removal were: mechanical obstruction by fibrin (8 cases/2.75%), obstruction by tub bower (1 case/0.34%), by omental muff (6 cases/2%); abdominal wall sepsis (30 cases/ 10.3%); non-responsive bacterial peritonitis (13 cases/4.05%), fungal peritonitis (7 cases/ 2.4%), fecal peritonitis (2 cases/0.68%); transfer to hemodialysis program (31 cases/10.6%); renal transplant (11 cases/3.79%); emergency surgical pathology for: necrotic-hemorrhagic pancreatitis (two cases), intestinal occlusions (six cases), locked hernias (three cases) and locked eventrations(three cases), appendicular peritonitis (two cases). Mortality associated with these procedures and underlying pathology was 1.73%.}, }
@article {pmid16596146, year = {2006}, author = {Dawson, MA and Polizzotto, MN and Gordon, A and Roberts, SK and Spencer, A}, title = {Extramedullary relapse of multiple myeloma presenting as hematemesis and melena.}, journal = {Nature clinical practice. Oncology}, volume = {3}, number = {4}, pages = {223-6; quiz 227}, doi = {10.1038/ncponc0454}, pmid = {16596146}, issn = {1743-4254}, mesh = {Diagnosis, Differential ; Female ; Hematemesis/*diagnosis/pathology ; Humans ; Melena/*diagnosis/pathology ; Middle Aged ; Multiple Myeloma/*diagnosis/pathology/therapy ; Recurrence ; Stem Cell Transplantation ; }, abstract = {BACKGROUND: A 60-year-old woman with multiple myeloma relapsed after a good partial response to high-dose chemotherapy (melphalan 200 mg/m(2)) and autologous stem-cell transplantation, followed by thalidomide and prednisolone maintenance therapy. She presented with hematemesis and melena following salvage chemotherapy with dexamethasone, cyclophosphamide, etoposide, cisplatin, and rescue therapy with single-agent bortezomib.<br><br>INVESTIGATIONS: Physical examination, laboratory investigations, gastroscopy, 2-[(18)F]fluoro-2-deoxyglucose-PET (FDG-PET), breast biopsy and histology.<br><br>DIAGNOSIS: Multifocal extramedullary relapse of multiple myeloma involving the stomach and duodenum.<br><br>MANAGEMENT: High-dose infusion of omeprazole, blood product support, palliative analgesics and anxiolytic agents.}, }
@article {pmid16573607, year = {2006}, author = {John, M and Gondolesi, G and Herold, BC and Kaufman, S and Fishbein, T and Posada, R}, title = {Impact of surveillance stool culture guided selection of antibiotics in the management of pediatric small bowel transplant recipients.}, journal = {Pediatric transplantation}, volume = {10}, number = {2}, pages = {198-204}, doi = {10.1111/j.1399-3046.2005.00424.x}, pmid = {16573607}, issn = {1397-3142}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Child ; Child, Preschool ; Cross Infection/microbiology ; Feces/*microbiology ; Female ; Humans ; Immunocompromised Host ; Infant ; Intestine, Small/*transplantation ; Male ; Microbial Sensitivity Tests ; Population Surveillance ; Postoperative Complications/*drug therapy/*microbiology ; Retrospective Studies ; }, abstract = {Surveillance stool cultures (SSC) have been used in immunocompromised populations to predict the organisms associated with invasive infections and aid in the selection of empiric antibiotic regimens. To evaluate the utility of this approach in pediatric small bowel transplant (SBT) recipients, we conducted a retrospective review of 33 patients who underwent SBT, 16 of whom had SSC done. In no case was the same organism isolated from SSC and subsequent blood, peritoneal fluid or wound cultures. In the first month post-transplantation, blood cultures were positive in 44% and 35% of patients that had and did not have SSC done, respectively (p = 0.73); peritoneal fluid cultures in 44% and 65% (p = 0.30); and wound cultures in 44% and 24% (p = 0.28). There were no significant differences among both groups in time to first infection, duration of ICU stay following SBT, graft survival or long-term patient survival. We conclude that SSC-guided antibiotic selection does not have a significant impact on the incidence of invasive infections in the first month following SBT or on specific indicators of patient outcome. This suggests that empiric antibiotic regimens should be selected based on clinical presentation and hospital flora and susceptibility patterns.}, }
@article {pmid16573593, year = {2006}, author = {Nolt, DL and Green, M}, title = {Surveillance stool cultures: to collect or not collect, that is the question.}, journal = {Pediatric transplantation}, volume = {10}, number = {2}, pages = {133-135}, doi = {10.1111/j.1399-3046.2005.00479.x}, pmid = {16573593}, issn = {1397-3142}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Child ; Cross Infection/microbiology ; Feces/*microbiology ; Humans ; Intestine, Small/*transplantation ; Microbial Sensitivity Tests ; Postoperative Complications/drug therapy/*microbiology ; }, }
@article {pmid16563562, year = {2006}, author = {Pearman, JW}, title = {2004 Lowbury Lecture: the Western Australian experience with vancomycin-resistant enterococci - from disaster to ongoing control.}, journal = {The Journal of hospital infection}, volume = {63}, number = {1}, pages = {14-26}, doi = {10.1016/j.jhin.2005.10.017}, pmid = {16563562}, issn = {0195-6701}, mesh = {Bacterial Proteins/*drug effects/isolation &amp; purification ; Carrier State/diagnosis ; Cross Infection/*epidemiology/microbiology ; *Disease Outbreaks ; Electrophoresis, Gel, Pulsed-Field ; Enterococcus faecium/*pathogenicity ; Gram-Positive Bacterial Infections/*epidemiology/transmission ; Humans ; Infection Control/economics/*methods ; *Vancomycin Resistance ; Western Australia/epidemiology ; }, abstract = {The first hospital outbreak of a vancomycin-resistant enterococcus (VRE) in Western Australia (WA) started in the Royal Perth Hospital in July 2001 and initially involved the Intensive Care Unit (ICU) and the Nephrology and Dialysis Units. The outbreak was caused by vancomycin-resistant Enterococcus faecium (VREF) of the vanB genotype. Pulsed-field gel electrophoresis and plasmid analysis of the isolates demonstrated a single-strain outbreak. Despite the isolation of carriers and implementation of all the additional precautions recommended to control VRE, VREF spread rapidly. Two months after the index patient was detected, the epidemic strain had spread to 22 wards and units and one outpatient unit (Satellite Dialysis). Four patients were infected and 64 were colonized. A Hospital VRE Executive Group, which included the Chief Executive and Directors of Clinical Services and Nursing, was formed to eradicate the outbreak and to prevent the epidemic strain from becoming endemic in the hospital. The WA Department of Health agreed to provide substantial extra funding to enable the hospital to use expensive enhanced infection control practices, as follows. Control was handicapped by the slowness of conventional laboratory methods, which took four to five days to identify VRE and allowed environmental contamination and nosocomial transmission to occur before carriers were detected and isolated. A laboratory procedure to make rapid provisional identification of VRE within 30-48h was developed by performing multiplex polymerase chain reaction (PCR) for vanA and vanB genes directly on 24-h selective enrichment broth cultures. On average, four rectal swabs, each collected on separate days, were needed to detect >90% of carriers. In total, 1977 ward contacts were screened after discharge from hospital and 54 (2.73%) were found to be carrying VREF. The electronic labelling and active follow-up of ward contacts resulted in a significant number of carriers being detected who otherwise posed a risk of initiating further outbreaks in hospital if they were re-admitted. The outbreak was terminated after five months and the cost of the enhanced infection control practices was 2,700 000 Australian dollars (1,000,000 pounds sterlings). Ongoing control has been facilitated by targeted active surveillance cultures: on admission to high-risk units (ICU, Burns, Nephrology, Haematology, Bone Marrow Transplant Unit), on transfer out of the ICU to other hospital units, by monthly screening of patients regularly attending Dialysis Units, and by opportunistic laboratory screening of inpatient faecal specimens submitted for Clostridium difficile culture and toxin. Vigilance needs to be maintained as the epidemic strain of VREF remains in the Perth community. Ward contacts of the first outbreak have caused small outbreaks in two hospitals, and seven to 19 sporadic new carriers have been detected annually since the first outbreak. The key elements of the VRE control programme are as follows: To date, this programme has prevented VRE from becoming established in any WA hospital.}, }
@article {pmid16554983, year = {2006}, author = {Belyaev, O and Müller, C and Uhl, W}, title = {Neosphincter surgery for fecal incontinence: a critical and unbiased review of the relevant literature.}, journal = {Surgery today}, volume = {36}, number = {4}, pages = {295-303}, pmid = {16554983}, issn = {0941-1291}, mesh = {Anal Canal/innervation/*surgery ; Anastomosis, Surgical/*methods ; Biliary Tract Surgical Procedures/*methods ; Electric Stimulation ; Fecal Incontinence/*surgery ; Humans ; Muscle, Smooth/*transplantation ; Nerve Transfer ; Postoperative Complications ; Plastic Surgery Procedures/methods ; }, abstract = {Up until about 15 years ago the only realistic option for end-stage fecal incontinence was the creation of a permanent stoma. There have since been several developments. Dynamic graciloplasty (DGP) and artificial bowel sphincter (ABS) are well-established surgical techniques, which offer the patient a chance for continence restoration and improved quality of life; however, they are unfortunately associated with high morbidity and low success rates. Several trials have been done in an attempt to clarify the advantages and disadvantages of these methods and define their place in the second-line treatment of severe, refractory fecal incontinence. This review presents a critical and unbiased overview of the current status of neosphincter surgery according to the available data in the world literature.}, }
@article {pmid16483042, year = {2005}, author = {Elbarrany, WG and Al-Hayani, A and Softa, S}, title = {The blood and nerve supply of the long head of the biceps femoris muscle; its possible use in dynamic neoanal sphincter.}, journal = {West African journal of medicine}, volume = {24}, number = {4}, pages = {287-294}, doi = {10.4314/wajm.v24i4.28196}, pmid = {16483042}, issn = {0189-160X}, mesh = {Anal Canal/physiology/*surgery ; Cadaver ; Fecal Incontinence/*surgery ; Humans ; Muscle Contraction/physiology ; Muscle, Skeletal/physiology/*transplantation ; Pilot Projects ; Plastic Surgery Procedures/*methods ; Thigh/*surgery ; }, abstract = {OBJECTIVES: Dynamic graciloplasty is used commonly as a neoanal sphincter to reconstruct the damaged anal sphincter. However, infection of the transposed gracilis and consequent failure of anal reconstruction has been recorded in some cases. An alternative to gracilis muscle should be searched for to reconstruct and replace the anal sphincter.<br><br>STUDY DESIGN: 30 fresh cadavers (20 adult, 10 stillborns) had been used in this study.<br><br>MATERIALS AND METHODS: The external and common iliac arteries were injected with a mixture of 50% lead oxide and 50% red latex. The long head of biceps femoris was exposed to identify its neurovascular bundle and estimate the whole length of the thigh, the whole length of the long head of biceps and the dominant neurovascular pedicles of the long head of biceps muscle. The functional length of the biceps muscle that is used during the muscle rotation was also calculated. The diameter of the arteries supplying the muscle was measured at their proximal and distal ends using a Swiss mechanic caliber. The thighs of both sides of each cadaver were X-rayed in order to study the vascular architecture of the muscle, and then the biceps muscle was dissected and removed then X-rayed to study the internal vasculature and anastomosis.<br><br>RESULTS: The study showed that there were four dominant arterial pedicles to the long head of biceps femoris muscle in addition to several minor arterial branches in 90% of the studied cases. In all cases, the inferior gluteal artery gave one major arterial pedicle to the proximal end of the muscle. The radiological study of the vasculature of the long head of biceps muscle during the current study showed the presence of anastomosing arterial loops between the internal iliac, external iliac, femoral and profunda femoris arteries. It also showed the presence of extensive intramuscular anastomosis between the intramuscular branches of the major arterial pedicles inside the long head of biceps femoris muscle. During the present study, it was found that the muscle received a single nerve supply in 97% of the dissected cadavers. This means that about in 58% of the cases, the muscle is available for transposition to wrap the anal canal. The available length of the muscle for rotation was about 57% of the length of the thigh.<br><br>CONCLUSION: It can be concluded that, the long head of the biceps muscle can be safely rotated to wrap around the anal canal without serious effect on the main vascular pedicles and its nerve supply.}, }
@article {pmid16464476, year = {2006}, author = {Miura, D and Ito, Y and Mizukuchi, A and Kise, M and Aoto, H and Yagasaki, K}, title = {Hypocholesterolemic action of pre-germinated brown rice in hepatoma-bearing rats.}, journal = {Life sciences}, volume = {79}, number = {3}, pages = {259-264}, doi = {10.1016/j.lfs.2006.01.001}, pmid = {16464476}, issn = {0024-3205}, mesh = {Animals ; Bile Acids and Salts/analysis/metabolism ; Carcinoma, Hepatocellular/complications/*metabolism ; Cholesterol/*metabolism ; Cholesterol 7-alpha-Hydroxylase/analysis/metabolism ; Feces/chemistry ; Germination ; Hypercholesterolemia/*diet therapy/enzymology/etiology ; Liver Neoplasms, Experimental/complications/*metabolism ; Neoplasm Transplantation ; *Oryza/growth &amp; development ; Rats ; Rats, Inbred Strains ; }, abstract = {The effect of pre-germinated brown rice (PGBR) on cholesterol metabolism was studied in Donryu rats subcutaneously implanted with the ascites hepatoma cell line AH109A and compared with that of white rice (WR). The effect of brown rice (BR), the source of PGBR, was also studied. Hepatoma-bearing rats fed a WR diet exhibited hypercholesterolemia compared with normal rats fed the same diet. Feeding hepatoma-bearing rats a PGBR or BR diet suppressed hepatoma-induced hypercholesterolemia, and enhanced fecal bile acid excretion and the activity of cholesterol 7alpha-hydroxylase, the rate-limiting enzyme of bile acid biosynthesis, in the microsomal fraction of the liver without affecting cholesterol synthesis in the host liver of hepatoma-bearing rats. These results suggest that PGBR as well as BR suppresses hypercholesterolemia induced by hepatoma growth by up-regulating cholesterol catabolism.}, }
@article {pmid16436893, year = {2006}, author = {Ranganathan, N and Patel, BG and Ranganathan, P and Marczely, J and Dheer, R and Pechenyak, B and Dunn, SR and Verstraete, W and Decroos, K and Mehta, R and Friedman, EA}, title = {In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease.}, journal = {ASAIO journal (American Society for Artificial Internal Organs : 1992)}, volume = {52}, number = {1}, pages = {70-79}, doi = {10.1097/01.mat.0000191345.45735.00}, pmid = {16436893}, issn = {1058-2916}, support = {1R44 DK 55403/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bioreactors/microbiology ; Blood Urea Nitrogen ; Body Weight ; Evaluation Studies as Topic ; Female ; Humans ; In Vitro Techniques ; Intestines/*microbiology ; Kidney Failure, Chronic/*therapy ; Male ; Nephrectomy ; Pilot Projects ; Probiotics/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Survival ; Urea/metabolism ; Uremia/metabolism/microbiology ; }, abstract = {Chronic kidney disease may progress to end-stage renal disease, which requires dialysis or kidney transplantation. No generally applicable therapies to slow progression of renal disease are available. Bacteriotherapy affords a promising approach to mitigate uremic intoxication by ingestion of live microbes able to catabolize uremic solutes in the gut. The present study evaluates the nonpathogenic soil-borne alkalophilic urease-positive bacterium Sporosarcina pasteurii (Sp) as a potential urea-targeted component for such "enteric dialysis" formulation. Data presented herein suggest that Sp survives through exposure to gastric juice retaining the ability to hydrolyze urea. In vitro, 10 cfu (colony forming units) of Sp removed from 21 +/- 4.7 mg to 228 +/- 6.7 mg urea per hour, depending on pH, urea concentration, and nutrient availability. Beneficial effects of Sp on fermentation parameters in the intestine were demonstrated in vitro in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) inoculated with fecal microbiota. Enumeration of marker organisms suggested that presence of Sp does not disturb microbial community of the SHIME. Additionally, a pilot study in 5/6th nephrectomized rats fed 10 cfu of live Sp daily throughout the study demonstrated that the tested regimen reduced blood urea-nitrogen levels and significantly prolonged the lifespan of uremic animals.}, }
@article {pmid16421440, year = {2006}, author = {Koornstra, JJ and Peeters, PM and van den Berg, AP and van der Jagt, EJ}, title = {Photo quiz. Melaena in a liver transplant recipient.}, journal = {The Netherlands journal of medicine}, volume = {64}, number = {1}, pages = {28,30}, pmid = {16421440}, issn = {0300-2977}, mesh = {Adult ; Anastomosis, Roux-en-Y/*adverse effects ; Female ; Humans ; Hypertension, Portal/*diagnostic imaging ; Liver Transplantation/*adverse effects ; Melena/*etiology ; Portal Vein/diagnostic imaging ; Radiography, Abdominal ; Tomography, X-Ray Computed ; }, }
@article {pmid16418694, year = {2006}, author = {Leung, LY and Lim, HK and Abell, MW and Zimmerman, JJ}, title = {Pharmacokinetics and metabolic disposition of sirolimus in healthy male volunteers after a single oral dose.}, journal = {Therapeutic drug monitoring}, volume = {28}, number = {1}, pages = {51-61}, doi = {10.1097/01.ftd.0000179838.33020.34}, pmid = {16418694}, issn = {0163-4356}, mesh = {Administration, Oral ; Adult ; Area Under Curve ; Chromatography, High Pressure Liquid ; Humans ; Immunosuppressive Agents/blood/metabolism/*pharmacokinetics ; Male ; Sirolimus/blood/metabolism/*pharmacokinetics ; Tissue Distribution ; }, abstract = {The pharmacokinetics and metabolic disposition of sirolimus (rapamycin, Rapamune), a macrocyclic immunosuppressive agent for the prevention of allograft rejection in organ transplantation, were investigated in 6 healthy male volunteers after a single nominal 40-mg oral dose of the C-radiolabeled drug, with the added aim of assessing the potential role of sirolimus metabolites in the clinical pharmacology of the parent drug. The absorption of parent drug and derived materials was rapid (tmax 1.3 +/- 0.5 hours, mean +/- SD), and the elimination of sirolimus was slow (t(1/2) 60 +/- 10 hours, mean +/- SD) in whole blood. The high whole blood to plasma (B/P) concentration ratio of sirolimus (142 +/- 39) was consistent with its extensive partitioning into formed blood elements. The markedly lower B/P value based on radioactivity (2.7 +/- 0.4) suggested that drug-derived products partitioned into formed blood elements to a much lesser extent. Based on AUC0-144h values, unchanged sirolimus represented an average 35% of total radioactivity in whole blood. Drug-derived products in whole blood were characterized by HPLC, LC/MS, and LC/MS/MS as 41-O-demethyl, 7-O-demethyl, and several hydroxy, dihydroxy, hydroxy-demethyl and didemethyl sirolimus metabolites. The percentage distribution of sirolimus metabolites in whole blood ranged from 3%-10% at 1 hour to 6%-17% at 24 hours after drug administration. Based on their low immunosuppressive activities and relative abundance in whole blood of humans after sirolimus administration, metabolites of sirolimus do not appear to play a major role in the clinical pharmacology of the parent drug. A majority of the administered radioactivity (91.0 +/- 8.0%) was recovered from feces, and only 2.2% +/- 0.9% was renally excreted.}, }
@article {pmid16370303, year = {2005}, author = {Mavinkurve, G and Pradilla, G and Legnani, FG and Tyler, BM and Bagley, CA and Brem, H and Jallo, G}, title = {A novel intramedullary spinal cord tumor model: functional, radiological, and histopathological characterization.}, journal = {Journal of neurosurgery. Spine}, volume = {3}, number = {2}, pages = {142-148}, doi = {10.3171/spi.2005.3.2.0142}, pmid = {16370303}, issn = {1547-5654}, mesh = {Animals ; *Disease Models, Animal ; Disease Progression ; Fecal Incontinence/etiology ; Magnetic Resonance Imaging ; Male ; Neoplasm Transplantation ; Paraparesis/etiology ; *Rabbits ; Spinal Cord Neoplasms/complications/*diagnosis/pathology/*physiopathology ; Urinary Incontinence/etiology ; }, abstract = {OBJECT: Survival rates for high-grade intramedullary spinal cord tumors (IMSCTs) are approximately 30%, and optimal therapy has yet to be determined. Development of a satisfactory intramedullary tumor model is necessary for testing new therapeutic paradigms that may prolong survival. The authors report the technique, functional progression, radiological appearance, and histopathological features of a novel intramedullary model in rabbits.<br><br>METHODS: Ten New Zealand white rabbits were randomized to receive an intramedullary injection of either 25 microl of VX2 carcinoma cells (500,000 cells; six rabbits) or 25 microl of medium (Dulbecco modified Eagle medium; four rabbits) into the midthoracic spinal cord. Postoperatively the rabbits were evaluated twice daily for neurological deficits. High-resolution magnetic resonance (MR) images were acquired preoperatively and weekly postoperatively until onset of paraparesis, at which point the animals were killed, and the midthoracic spines were processed for histopathological examination. The VX2-carcinoma cells grew in 100% of animals injected and resulted in a statistically significant mean onset of paraparesis of 16.8 +/- 1.7 days (p = 0.0035, log-rank test), compared with animals in the control group in which neurological deficits were absent by Day 45. Contrast-enhanced T1-weighted MR imaging best demonstrated space-occupying intramedullary lesions and histopathological findings confirmed the intramedullary location of the tumor. Animals in the control group exhibited no functional, radiographic, or pathological signs of tumor.<br><br>CONCLUSIONS: Progression to paraparesis was consistent in all the VX2-injected animals, with predictable onset of paraparesis occurring approximately 17 days postinjection. Histopathological and radiological characteristics of the VX2 intramedullary tumor are comparable with those of aggressive primary human IMSCTs. Establishment of this novel animal tumor model will facilitate the testing of new therapeutic paradigms for the treatment of IMSCTs.}, }
@article {pmid16333075, year = {2005}, author = {Goldenberg, O and Herrmann, S and Adam, T and Marjoram, G and Hong, G and Göbel, UB and Graf, B}, title = {Use of denaturing high-performance liquid chromatography for rapid detection and identification of seven Candida species.}, journal = {Journal of clinical microbiology}, volume = {43}, number = {12}, pages = {5912-5915}, pmid = {16333075}, issn = {0095-1137}, mesh = {Blood/microbiology ; Candida/*classification/genetics/*isolation &amp; purification ; Candidiasis/diagnosis/microbiology ; Chromatography, High Pressure Liquid/methods ; Culture Media ; DNA, Fungal/analysis/isolation &amp; purification ; DNA, Ribosomal Spacer/analysis ; Feces/microbiology ; Fungemia/diagnosis/microbiology ; Humans ; *Mycological Typing Techniques ; Polymerase Chain Reaction/*methods ; Species Specificity ; Time Factors ; }, abstract = {A novel denaturing high-performance liquid chromatography (DHPLC)-based technique allows rapid high-resolution analysis of PCR products. We used this technique for unequivocal molecular identification of seven Candida species. We show the application of this PCR/DHPLC approach for direct detection and identification of yeast species from blood cultures and for detection of Candida colonization in the gastrointestinal tract of allogeneic transplant patients.}, }
@article {pmid16314073, year = {2006}, author = {Ged, C and Mendez, M and Robert, E and Lalanne, M and Lamrissi-Garcia, I and Costet, P and Daniel, JY and Dubus, P and Mazurier, F and Moreau-Gaudry, F and de Verneuil, H}, title = {A knock-in mouse model of congenital erythropoietic porphyria.}, journal = {Genomics}, volume = {87}, number = {1}, pages = {84-92}, doi = {10.1016/j.ygeno.2005.08.018}, pmid = {16314073}, issn = {0888-7543}, mesh = {*Amino Acid Substitution ; Animals ; Bone Marrow Transplantation ; Disease Models, Animal ; Genetic Therapy ; Mice ; Mice, Transgenic ; *Mutation, Missense ; Porphyria, Erythropoietic/*enzymology/pathology/therapy ; Uroporphyrinogen III Synthetase/*genetics/metabolism ; Uroporphyrins/metabolism ; }, abstract = {Congenital erythropoietic porphyria (CEP) is a recessive autosomal disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthetic pathway. The severity of the disease, the lack of specific treatment except for allogeneic bone marrow transplantation, and the knowledge of the molecular lesions are strong arguments for gene therapy. An animal model of CEP has been designed to evaluate the feasibility of retroviral gene transfer in hematopoietic stem cells. We have previously demonstrated that the knockout of the Uros gene is lethal in mice (Uros(del) model). This work describes the achievement of a knock-in model, which reproduces a mutation of the UROS gene responsible for a severe UROS deficiency in humans (P248Q missense mutant). Homozygous mice display erythrodontia, moderate photosensitivity, hepatosplenomegaly, and hemolytic anemia. Uroporphyrin (99% type I isomer) accumulates in urine. Total porphyrins are increased in erythrocytes and feces, while Uros enzymatic activity is below 1% of the normal level in the different tissues analyzed. These pathological findings closely mimic the CEP disease in humans and demonstrate that the Uros(mut248) mouse represents a suitable model of the human disease for pathophysiological, pharmaceutical, and therapeutic purposes.}, }
@article {pmid16302085, year = {2005}, author = {Kestering, Dde M and d'Acampora, AJ and Farias, DC and Brum, SP and Ely, JB}, title = {[Rats resistance to fecal peritonitis when subjected to total splenectomy and auto-implant of the spleen in the retroperitoneum].}, journal = {Acta cirurgica brasileira}, volume = {20}, number = {6}, pages = {473-477}, doi = {10.1590/s0102-86502005000600014}, pmid = {16302085}, issn = {0102-8650}, mesh = {Age Factors ; Animals ; Feces/microbiology ; Peritonitis/*prevention &amp; control ; Rats ; Rats, Wistar ; Retroperitoneal Space/*surgery ; Spleen/*transplantation ; *Splenectomy ; Time Factors ; Transplantation, Autologous ; }, abstract = {PURPOSE: This study was developed to evaluated the effects of spleen transplants in the protection against abdominal sepsis in young and old Wistar rats.<br><br>METHODS: Fifty-four young and old Wistar rats were utilized (90 and 180 days respectively) being distributed in three groups as follows: Sham Group, where the animal were submitted to laparotomy with manipulation of only intestine (n=12 young and adult animals), Splenectomy Group, in which the animals were subjected to total splenectomy (n=20 young and adult animals) and an Auto-implant Group, where the animals were subjected to total splenectomy and a third of the spleen was implanted in a bag in the retroperitoneum (n=22 young and adult animals). After three months the animals were subjected to a new laparotomy with binding and caecum perforation to stimulate abdominal sepsis and were accompanied until the moment of death to establish a mortality curve.<br><br>RESULTS: There was recuperation of the spleen implanted in all animals. There was no significant difference in the time of death among the groups. The young animals apparently had a better response, however it was not statistically significant.<br><br>CONCLUSION: This study demonstrated that spleen implant in the retroperitoneum do not prove to be an effective protection against abdominal sepsis in comparison with the splenectomized rats.}, }
@article {pmid16269283, year = {2005}, author = {Escobar, MA and Grosfeld, JL and Burdick, JJ and Powell, RL and Jay, CL and Wait, AD and West, KW and Billmire, DF and Scherer, LR and Engum, SA and Rouse, TM and Ladd, AP and Rescorla, FJ}, title = {Surgical considerations in cystic fibrosis: a 32-year evaluation of outcomes.}, journal = {Surgery}, volume = {138}, number = {4}, pages = {560-71; discussion 571-2}, doi = {10.1016/j.surg.2005.06.049}, pmid = {16269283}, issn = {0039-6060}, mesh = {Abdomen/surgery ; Adolescent ; Adult ; Bile Duct Diseases/etiology/*surgery ; Child ; Child, Preschool ; Cystic Fibrosis/*complications/metabolism/mortality ; Female ; Humans ; Ileus/etiology/*surgery ; Infant ; Infant, Newborn ; Intestinal Diseases/etiology/*surgery ; Intussusception/etiology/surgery ; Liver Diseases/etiology/*surgery ; Male ; Meconium/metabolism ; Pneumothorax/etiology/*surgery ; Postoperative Complications ; Retrospective Studies ; Survival Analysis ; Thoracic Surgical Procedures/adverse effects ; Treatment Outcome ; }, abstract = {BACKGROUND: Information concerning long-term operative outcomes in patients with cystic fibrosis (CF) is relatively sparse in the operative literature.<br><br>METHODS: A retrospective review of CF patients with operative conditions was performed (1972-2004) at a tertiary children's hospital to analyze outcomes including long-term morbidity and survival.<br><br>RESULTS: A total of 226 patients with CF presented with an operative diagnosis (113 men, 113 women). A total of 422 operations were performed in 213 patients (94%). The mean age at operation was 4.1 +/- 6.2 years (range, 1 d to 26 y) and 109 were neonates. Fifteen of 42 (36%) babies with simple meconium ileus (MI) were treated nonoperatively with hypertonic enemas, 27 of 42 and all 45 patients with complicated MI required operation, including 15 with jejunoileal atresia (17%). Seventeen of 27 (63%) patients with meconium ileus equivalent had MI as neonates; 7 of 27 (26%) required operation. Eight of 9 (89%) with fibrosing colonopathy required operation. Organ transplantation was required in 21 patients. Follow-up evaluation was possible in 204 of 213 (96%) patients. The duration of follow-up evaluation was 14.9 +/- 8.5 years (range, 2 mo to 35 y). Operative morbidity was 11% at 1 year, 2% at 2 to 4 years, 1% at 5 to 10 years, and less than 1% at more than 10 years. There were 24 deaths (11%); 22 followed CF-related pulmonary complications and included 8 of 16 (50%) children with pneumothorax.<br><br>CONCLUSIONS: Long-term survival in CF patients has improved significantly (89%), with many surviving into the fourth decade. MI may predispose to late complications including meconium ileus equivalent and fibrosing colonopathy. Pneumothorax in CF patients is an ominous predictor of mortality. Children with CF are living longer and are good candidates for operation, but require long-term follow-up evaluation because of ongoing exocrine dysfunction.}, }
@article {pmid16252141, year = {2005}, author = {Neri, E and Vagli, P and Picchietti, S and Vannozzi, F and Linsalata, S and Bardine, A and Bartolozzi, C}, title = {CT colonography: contrast enhancement of benign and malignant colorectal lesions versus fecal residuals.}, journal = {Abdominal imaging}, volume = {30}, number = {6}, pages = {694-697}, doi = {10.1007/s00261-005-0340-6}, pmid = {16252141}, issn = {0942-8925}, mesh = {Colonic Polyps/diagnostic imaging ; Colonography, Computed Tomographic/*methods ; Colorectal Neoplasms/*diagnostic imaging ; Contrast Media ; Diagnosis, Differential ; *Feces ; Humans ; Image Enhancement/methods ; Retrospective Studies ; }, abstract = {We retrospectively reviewed the computed tomographic colonographic datasets of 22 patients. Mean attenuation values of benign polyps before and after contrast administration were 30 +/- 15 HU and 90 +/- 18 HU, respectively. Mean attenuation values of colorectal cancer before and after contrast administration were 43 +/- 15 HU and 124 +/- 18 HU, respectively. The mean attenuation value of solid fecal residuals was 43 +/- 15 HU. The difference in attenuation value between precontrast and postcontrast studies of polyps was statistically significant (mean 60 HU, p < 0.01); the same was true for colorectal cancer (mean 81 HU, p < 0.01). The difference between postcontrast density of polyps and cancer with respect to density of solid fecal residuals was statistically significant (p < 0.01). The use of contrast medium could be of help in computed tomographic colonography for discriminating polypoid benign lesions and colorectal cancer from fecal residuals.}, }
@article {pmid16246412, year = {2006}, author = {Stabili, L and Licciano, M and Giangrande, A and Fanelli, G and Cavallo, RA}, title = {Sabella spallanzanii filter-feeding on bacterial community: ecological implications and applications.}, journal = {Marine environmental research}, volume = {61}, number = {1}, pages = {74-92}, doi = {10.1016/j.marenvres.2005.06.001}, pmid = {16246412}, issn = {0141-1136}, mesh = {Analysis of Variance ; Animals ; Bacteria/*growth &amp; development/isolation &amp; purification ; Colony Count, Microbial ; *Ecosystem ; Enterobacteriaceae/growth &amp; development/isolation &amp; purification ; Linear Models ; Oxygen/analysis ; Polychaeta/*microbiology ; Population Dynamics ; Random Allocation ; Seasons ; Seawater/analysis/*microbiology ; Sodium Chloride/analysis ; Starvation ; Streptococcus/growth &amp; development/isolation &amp; purification ; Temperature ; *Water Microbiology ; }, abstract = {The filtration process of Sabella spallanzanii Gmelin on bacterial community was studied in a coastal area of the Northern Ionian Sea (Mediterranean Sea) at three sites, S. Vito, Lido Gandoli and Lido Silvana, where some specimens of S. spallanzanii were transplanted. Analyses were performed both on water and worm samples. A total of six microbial groups were examined: culturable heterotrophic bacteria, total culturable bacteria at 37 degrees C, culturable vibrios, total and fecal coliforms and fecal streptococci. The bacterial densities were usually orders of magnitude higher in the worm homogenates than in the corresponding seawater and the highest values were observed in August. The ability of S. spallanzanii to accumulate the microbial pollution indicators suggests this species can be employed as a bioindicator for monitoring water quality. Moreover, the accumulation capability of S. spallanzanii for specific micro-organisms provides a potential role in sewage bioremediation.}, }
@article {pmid16207968, year = {2005}, author = {Aabenhus, R and On, SL and Siemer, BL and Permin, H and Andersen, LP}, title = {Delineation of Campylobacter concisus genomospecies by amplified fragment length polymorphism analysis and correlation of results with clinical data.}, journal = {Journal of clinical microbiology}, volume = {43}, number = {10}, pages = {5091-5096}, pmid = {16207968}, issn = {0095-1137}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacterial Typing Techniques ; Campylobacter/*classification/*genetics/isolation &amp; purification/pathogenicity ; Campylobacter Infections/immunology/microbiology/*physiopathology ; Child ; Child, Preschool ; Diarrhea/immunology/microbiology/*physiopathology ; Female ; Humans ; Immunocompetence ; Immunocompromised Host ; Infant ; Male ; Middle Aged ; *Polymorphism, Restriction Fragment Length ; Species Specificity ; Virulence ; }, abstract = {Campylobacter concisus has been as frequently isolated from human diarrhea as the important enteropathogen Campylobacter jejuni, but it also occurs in the feces of healthy individuals. The role of C. concisus in human disease has been difficult to determine, since the species comprises at least two phenotypically indistinguishable but genetically distinct taxa (i.e., genomospecies) that may vary in pathogenicity. We examined 62 C. concisus strains by amplified fragment length polymorphism (AFLP) profiling and correlated the results with clinical data. All C. concisus strains gave unique AFLP profiles, and numerical analysis of these data distributed the strains among four clusters. The clustering was of taxonomic significance: two clusters contained, respectively, the type strain (of oral origin) and a reference strain (from diarrhea) of each of the known genomospecies. Genomospecies 2 strains were more frequently isolated from immunocompetent patients and/or patients without concomitant infections that presented with fever, chronic diarrhea, and gut inflammation than was genomospecies 1, clustering with the type strain of oral origin. Bloody diarrhea was recorded only with C. concisus genomospecies 2 infections. We identified two additional C. concisus genomospecies: genomospecies 3 comprised a single strain from an immunocompetent patient, and genomospecies 4 contained five isolates from severely immunodeficient patients, i.e., organ transplantation recipients or those with hematological malignancies. All genomospecies 4 strains were of the same protein profile group and failed to react with a C. concisus species-specific PCR assay based on 23S rRNA gene sequences: the taxonomic position of this group requires closer investigation. Campylobacter concisus is genetically and taxonomically diverse and contains at least four distinct genomospecies that may exhibit differences in their spectra of virulence potential.}, }
@article {pmid16107193, year = {2005}, author = {Groll, AH and Walsh, TJ}, title = {Posaconazole: clinical pharmacology and potential for management of fungal infections.}, journal = {Expert review of anti-infective therapy}, volume = {3}, number = {4}, pages = {467-487}, doi = {10.1586/14787210.3.4.467}, pmid = {16107193}, issn = {1744-8336}, mesh = {Animals ; Antifungal Agents/chemistry/*pharmacology/*therapeutic use ; Drug Resistance, Fungal ; Fungi/drug effects ; Humans ; Molecular Structure ; Mycoses/*drug therapy ; Triazoles/chemistry/*pharmacology/*therapeutic use ; }, abstract = {Posaconazole is a novel lipophilic antifungal triazole that inhibits cytochrome P450-dependent 14-alpha demethylase in the biosynthetic pathway of ergosterol. Inhibition of this enzyme leads to an accumulation of toxic 14-alpha methylsterols and a depletion of ergosterol, resulting in a perturbation of the function of the fungal cell membrane and blockage of cell growth and division. In vitro, posaconazole has potent and broad-spectrum activity against opportunistic, endemic and dermatophytic fungi. This activity extends to organisms that are often refractory to existing triazoles, amphotericin B or echinocandins, such as Candida glabrata, Candida krusei, Aspergillus terreus, Fusarium spp. and the Zygomycetes. A large variety of animal models of invasive fungal infections have provided consistent evidence of efficacy against these organisms in vivo, both in normal and immunocompromised animals. Posaconazole is available as an oral suspension and optimal exposure is achieved when the drug is administered in two to four divided doses along with food or a nutritional supplement. The compound has a large volume of distribution, in the order of 5 l/kg, and a half-life of approximately 20 h. Posaconazole is not metabolized to a significant extent through the cytochrome P450 enzyme system and is primarily excreted in an unchanged form in the feces. Although it is inhibitory, cytochrome P3A4 has no effect on 1A2, 2C8, 2C9, 2D6 and 2E1 isoenzymes, and therefore, a limited spectrum of drug-drug interactions can be expected. Pharmacokinetic studies in special populations revealed no necessity for dosage adjustment based on differences in age, gender, race, renal or hepatic function. Posaconazole has demonstrated strong antifungal efficacy in Phase II and III clinical trials in immunocompromised patients with oropharyngeal and esophageal candidiasis. Posaconazole also showed promising efficacy as salvage therapy in a large Phase II study including 330 patients with invasive fungal infections intolerant to or refractory to standard therapies. Posaconazole appears to be well tolerated in a manner comparable with that of fluconazole and it is currently under regulatory review in the USA and Europe for the treatment of refractory invasive fungal infections. This drug profile reviews the preclinical and clinical pharmacology of posaconazole and its potential role for prevention and treatment of invasive fungal infections.}, }
@article {pmid16098075, year = {2005}, author = {Kampmann, B and Cubitt, D and Walls, T and Naik, P and Depala, M and Samarasinghe, S and Robson, D and Hassan, A and Rao, K and Gaspar, H and Davies, G and Jones, A and Cale, C and Gilmour, K and Real, M and Foo, M and Bennett-Rees, N and Hewitt, A and Amrolia, P and Veys, P}, title = {Improved outcome for children with disseminated adenoviral infection following allogeneic stem cell transplantation.}, journal = {British journal of haematology}, volume = {130}, number = {4}, pages = {595-603}, doi = {10.1111/j.1365-2141.2005.05649.x}, pmid = {16098075}, issn = {0007-1048}, mesh = {*Adenoviridae/genetics ; Adenoviridae Infections/*complications ; Adolescent ; Antiviral Agents/therapeutic use ; Child ; Child, Preschool ; DNA, Viral/analysis/blood ; Feces/virology ; Ganciclovir/therapeutic use ; Hematologic Diseases/*surgery/virology ; Humans ; Immunosuppressive Agents/therapeutic use ; Infant ; Logistic Models ; Nasopharynx/virology ; Nose/virology ; Polymerase Chain Reaction/methods ; Prognosis ; Prospective Studies ; Risk Factors ; Stem Cell Transplantation/*adverse effects ; Transplantation Conditioning/methods ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {Adenovirus (AdV) infections are a frequent cause of morbidity and mortality following allogeneic stem cell transplantation (SCT), and disseminated infection is associated with high mortality, particularly in paediatric SCT. Here, we describe an approach to reduce mortality from adenoviraemia by combining prospective monitoring for the occurrence of adenoviraemia using a sensitive polymerase chain reaction method, early antiviral therapy and prompt withdrawal of immunosuppression. A total of 155 consecutive paediatric SCT procedures were prospectively monitored, of which 113 (73%) transplants involved donors other than matched siblings and 126 (83%) employed T-cell depletion. Adenoviraemia was detected in 26/155 (17%) transplants and developed exclusively in patients who had received T-cell-depleted grafts. Withdrawal of immunosuppression coupled with early antiviral therapy led to resolution of adenoviraemia in 19/26 (81%) patients with only five patients succumbing to disseminate AdV infection. Survival from adenoviraemia was associated with lymphocyte recovery to above 0.3x10(9)/l. Mortality was closely linked with the absence of lymphocyte recovery because of profound T-cell depletion of the graft with CD34+ magnetic-activated cell sorting. Mortality from disseminated AdV infection was 5/26 (19%) in this study, which is significantly lower than previously reported.}, }
@article {pmid16084458, year = {2005}, author = {Scott, RS and Sutton, DA and Jagirdar, J}, title = {Lung infection due to opportunistic fungus, Phialemonium obovatum, in a bone marrow transplant recipient: an emerging infection with fungemia and Crohn disease-like involvement of the gastrointestinal tract.}, journal = {Annals of diagnostic pathology}, volume = {9}, number = {4}, pages = {227-230}, doi = {10.1016/j.anndiagpath.2005.04.010}, pmid = {16084458}, issn = {1092-9134}, mesh = {Amphotericin B/therapeutic use ; Antifungal Agents/therapeutic use ; *Ascomycota ; Bone Marrow Transplantation ; Drug Resistance, Fungal ; Fungemia/drug therapy ; Gastrointestinal Diseases/*microbiology ; Graft vs Host Disease ; Granuloma/pathology ; Humans ; *Immunocompromised Host ; Itraconazole/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy ; Lung Diseases, Fungal/*complications/drug therapy/pathology ; Male ; Middle Aged ; Opportunistic Infections/*complications/drug therapy/pathology ; Pyrimidines/therapeutic use ; Triazoles/therapeutic use ; Voriconazole ; }, abstract = {We report the first case of Phialemonium obovatum fungemia with subsequent caseating granulomatas in the lung and Crohn disease-like involvement of the gastrointestinal tract in a bone marrow transplant recipient. This phaeoid fungus has been rarely described as an opportunistic infection in immunosuppressed patients. The patient was diagnosed with chronic myelogenous leukemia and underwent subsequent peripheral bone marrow transplant. After 6 months, he developed graft-versus-host disease of the skin and liver with fever and severe diarrhea. Fecal bacterial cultures and cytomegalovirus serologies were negative. Computed tomographic scan showed a peripheral pulmonary mass. A lung wedge biopsy of the lesion showed septate branching hyphae (4-5 microm in diameter) with terminal globular structures (10 microm in diameter). The hyphae were similar in width to that of an Aspergillus species but had a more moniliform appearance. Blood cultures grew a pure culture of P. obovatum. He was treated with amphotericin B and itraconazole for 6 months without remission of the diarrhea. Biopsies of the stomach, colon, and rectum showed granulomatous inflammation with marked crypt distortion simulating Crohn disease. In retrospect, the fungus was found to be resistant to both of the aforementioned drugs and susceptible to voriconazole and posaconazole. The gastrointestinal findings raise the possibility of further dissemination of a partially treated Phialemonium infection.}, }
@article {pmid16033769, year = {2005}, author = {Burdese, M and Veglio, V and Consiglio, V and Soragna, G and Mezza, E and Bergamo, D and Tattoli, F and Rossetti, M and Jeantet, A and Segoloni, GP and Piccoli, GB}, title = {A dance teacher with kidney-pancreas transplant and diarrhoea: what is the cause?.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {20}, number = {8}, pages = {1759-1761}, doi = {10.1093/ndt/gfh881}, pmid = {16033769}, issn = {0931-0509}, mesh = {Adult ; Animals ; Cryptosporidiosis/drug therapy/*parasitology ; Cryptosporidium parvum/*isolation &amp; purification ; Diarrhea/drug therapy/*parasitology ; Drug Therapy, Combination/therapeutic use ; Feces/parasitology ; Female ; Humans ; *Kidney Transplantation ; Mycophenolic Acid/analogs &amp; derivatives/therapeutic use ; *Pancreas Transplantation ; Parasite Egg Count ; Rifamycins/therapeutic use ; Rifaximin ; }, }
@article {pmid16022803, year = {2005}, author = {Tillin, T and Chambers, M and Feldman, R}, title = {Outcomes of electrically stimulated gracilis neosphincter surgery.}, journal = {Health technology assessment (Winchester, England)}, volume = {9}, number = {28}, pages = {iii, ix-xi, 1-102}, doi = {10.3310/hta9280}, pmid = {16022803}, issn = {1366-5278}, mesh = {Anal Canal/*surgery ; Cross-Sectional Studies ; *Electric Stimulation Therapy ; Fecal Incontinence/*surgery ; Humans ; Longitudinal Studies ; Muscle, Skeletal/*transplantation ; *Outcome Assessment, Health Care ; Prospective Studies ; Quality of Life ; Plastic Surgery Procedures ; Surgical Flaps ; Surgical Stomas ; Surveys and Questionnaires ; United Kingdom ; }, abstract = {OBJECTIVES: To examine patient quality of life (QoL) and long-term costs of electrically stimulated gracilis neosphincter surgery (ESGNS).<br><br>DESIGN: Independently conducted prospective case-comparison study of patients at the Royal London Hospital (RLH), plus a cross-sectional study of outcomes of ESGNS performed at three other UK centres.<br><br>PARTICIPANTS: Cases were patients who underwent ESGNS at the participating hospitals during a 5-year period from 1977. Comparisons were made with two groups of people with similar bowel disorders who did not undergo ESGNS.<br><br>INTERVENTION: ESGNS is a procedure designed to improve bowel function for people living with severe faecal incontinence or stomas. It involves transposition of the gracilis muscle to form a neo-anal sphincter. The transposed muscle is electrically stimulated via an electronic pulse generator implanted beneath the skin of the abdomen.<br><br>MAIN OUTCOME MEASURES: Clinical success and symptomatic outcomes of surgery. Generic, domain and condition specific measures of QoL. Comparative costs to the NHS of ESGNS and conventional alternatives.<br><br>RESULTS: At 3 years after surgery approximately three-quarters of patients still had functioning neosphincters. At this stage, bowel-related QoL and continence improved by more than 20% for nearly two-thirds of RLH patients. However, ongoing bowel evacuation difficulties occurred in half of those with good continence outcomes. QoL improvements were maintained in the smaller group of RLH patients who had reached 4 and 5 years of follow-up, although at this stage the proportion with failed neosphincters had increased. The RLH findings were supported by those from the three other UK centres. No significant changes in QoL were observed in the comparison groups during the follow-up period. The mean cost of patient care at RLH, was 23,253 pounds. In the other three centres, the estimated mean cost of the intervention per patient was 11,731 pounds, reflecting fewer planned operations and repeat admissions. Costs of patient care for those with stomas who did not undergo ESGNS were estimated at 2125 pounds per patient-year and for those who remained with severe faecal incontinence, 442 pounds per patient-year. For patients with prior faecal incontinence, a decision to refer to ESGNS resulted in a cost-effectiveness ratio, estimated over 25 years of follow-up, of between 30,000 pounds and 40,000 pounds per quality-adjusted life-year (QALY) gained, depending on centre. The choice of stoma for these patients resulted in a slightly higher cost than ESGNS. For those with prior stoma, referral to ESGNS resulted in a cost-effectiveness ratio of between 5000 pounds and 15,000 pounds per QALY gained, depending on the centre. Cost-effectiveness ratios of around 30,000 pounds per QALY gained are generally regarded to be reasonably attractive in the UK NHS context.<br><br>CONCLUSIONS: Although ESGNS is a major procedure associated with a high rate of long-term failure and bowel evacuation difficulty, it could be considered as an option at the extreme end of the treatment spectrum for refractory faecal incontinence. A strategy to refer patients for ESGNS would be regarded as cost-effective for patients already with stoma, whilst on the margin of cost-effectiveness for patients initially being managed conservatively.}, }
@article {pmid16007605, year = {2006}, author = {Castagnola, E and Calvillo, M and Gigliotti, AR and Fioredda, F and Hanau, G and Caviglia, I and Lanino, E and Dufour, C}, title = {Helicobacter pylori as cause of gastrointestinal disease in children with hemato-oncologic diseases.}, journal = {Pediatric blood &amp; cancer}, volume = {47}, number = {1}, pages = {89-91}, doi = {10.1002/pbc.20459}, pmid = {16007605}, issn = {1545-5009}, mesh = {Abdominal Pain/complications/microbiology ; Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Gastrointestinal Diseases/complications/*microbiology ; Helicobacter Infections/*complications ; *Helicobacter pylori ; Hematologic Diseases/*complications ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Immunocompromised Host ; Male ; Neoplasms/*complications ; }, abstract = {After documentation of a case of life threatening Helicobacter pylori (H. pylori) gastric ulcer in an adolescent girl on treatment for acute lymphoblastic leukaemia, we started to systematically look for gastro-intestinal symptoms due to H. pylori infection in our cancer patients at G. Gaslini Children's Hospital. During a period of 46 months, we observed 13 further cases of severe dyspepsia syndrome or gastro intestinal bleeding associated with presence of H. pylori faecal antigen. All patients recovered with appropriate therapy. H. pylori may represent a cause of severe gastrointestinal complications in children with cancer or following bone marrow transplant.}, }
@article {pmid15983737, year = {2005}, author = {Agirbasli, H and Ozcan, SA and Gedikoğlu, G}, title = {Fecal fungal flora of pediatric healthy volunteers and immunosuppressed patients.}, journal = {Mycopathologia}, volume = {159}, number = {4}, pages = {515-520}, pmid = {15983737}, issn = {0301-486X}, mesh = {Adolescent ; Adult ; Bone Marrow Transplantation ; Candida/*isolation &amp; purification ; Candidiasis/immunology/*microbiology ; Child ; Child, Preschool ; Feces/microbiology ; Female ; Hematologic Diseases/immunology/*microbiology ; Humans ; Immunocompromised Host ; Infant ; Male ; Retrospective Studies ; Statistics, Nonparametric ; }, abstract = {Most hematogenous candidiasis originates from endogeneous host flora. Fungal flora of gastrointestinal system are important source of infection especially in immunosupressed patients. The purpose of this study was to investigate the fecal fungal flora of pediatric patients with hematologic malignancy or disorders and to compare the results with healthy volunteers. For this purpose, fungal etiological agents were investigated retrospectively in stool samples of 80 patients followed in Bone marrow transplantation and Hematology-Oncology units. The diagnosis of patients were as follows: 26 acute myelogeneous leukemia, 19 acute lymphocytic leukemia, 5 lymphoma, 3 chronic myelogeneous leukemia, 2 solid tumor, 4 neuroblastoma and 21 hematologic disorders. In patients, totally 102 fungal growth was detected and 42 (41.2%) C. albicans and 51 (50%) non-albicans Candida species and 9 (8.8%) yeast other than Candida and mould was isolated. The results were compared prospectively with growth in stool samples of 61 healthy children. C. albicans was detected in 16 (43.2%) and non-albicans Candida species in 15 (40.5%) and yeasts other than Candida and mould in 6 (16.2%) of 37 fungal growth in controls. Non-albicans Candida species growth was found significantly higher and C. glabrata was more prevelant in patients than in controls (p < 0.001).}, }
@article {pmid15960282, year = {2005}, author = {Aziz, S and Anjum, S and Rehman, AU and Akram, DS and Naqvi, SA and Rizvi, SA}, title = {Bilirubin pigments in the first meconium of newborn infants.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {55}, number = {5}, pages = {188-192}, pmid = {15960282}, issn = {0030-9982}, mesh = {Bile Acids and Salts ; Bile Pigments/*analysis ; Bilirubin/analysis/*metabolism ; Biomarkers ; Chromatography, High Pressure Liquid ; Feces/*chemistry ; Gestational Age ; Humans ; Infant, Newborn/*metabolism ; Infant, Premature/metabolism ; Meconium/chemistry/*metabolism ; }, abstract = {OBJECTIVE: To determine the pattern of excretion of total bilirubin IXa and IXb in the first meconium of newborn infants.<br><br>METHODS: First two newborns of varying gestational age were selected every week through random sampling from the neonatal unit. Of the 41 newborn infants selected 8 expired before meconium passage, hence the results are from 33 newborns. Meconium was collected and stored at -20 degrees C, protected by aluminium foil. Samples were defrosted, vortex mixed with equal amount of dimethyl-sulfoxide, centrifuged, and analyzed by HPLC.<br><br>RESULTS: Unconjugated Bilirubin-IXalpha and -IXbeta were identified and quantitative estimation of Bilirubin-IXa done. Bilirubin-IXb was greater than 50% of the total, in the first meconium of the newborn. Amount of bilirubin excreted in meconium was 29.2 - 90.8 mg [0.051 - 0.155 mmol] per sample of meconium passed. Amount was 9.7 mg/ Kg of body weight in term newborn and 12 mg/kg in preterm.<br><br>CONCLUSION: The amount of bilirubin -IXb decreases and bilirubin-IXa increases with increasing gestational age. Newborns with birth asphyxia (BA) had significantly greater quantity of bilirubin in meconium, compared to infants without BA.}, }
@article {pmid15940181, year = {2005}, author = {Zakharash, MP and Poĭda, AI and Mel'nik, VM}, title = {[Abdomino-anal resection in the treatment of low-ampullar cancer of the rectum].}, journal = {Khirurgiia}, volume = {}, number = {4}, pages = {52-56}, pmid = {15940181}, issn = {0023-1207}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anal Canal/physiology/*surgery ; Anastomosis, Surgical ; Colon/surgery ; Fecal Incontinence/prevention &amp; control ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Postoperative Complications/prevention &amp; control ; Quality of Life ; Recovery of Function ; Rectal Neoplasms/*surgery ; Risk Factors ; Surveys and Questionnaires ; Time Factors ; Treatment Outcome ; }, abstract = {Surgical policy was developed for improvement of functional results and quality of life in patients operated on for low rectal cancer. This policy includes choice of the method of sphincter-saving operation depending on the stage of the tumor, grade of malignancy, distance from a low edge of the tumor to dentate line. Methods of prevention of ischemia and necrosis of brought down colonic transplant and anal incontinence were used. This increased the number of sphincter-saving operations in low location of rectal cancer by 35%, reduced the rate of necrosis of intestinal transplant from 7 to 4.4%, saved continent function and improved significantly quality of life in 89.8% operated patients.}, }
@article {pmid15888045, year = {2005}, author = {Lemahieu, W and Maes, B and Verbeke, K and Rutgeerts, P and Geboes, K and Vanrenterghem, Y}, title = {Cytochrome P450 3A4 and P-glycoprotein activity and assimilation of tacrolimus in transplant patients with persistent diarrhea.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {5}, number = {6}, pages = {1383-1391}, doi = {10.1111/j.1600-6143.2005.00844.x}, pmid = {15888045}, issn = {1600-6135}, mesh = {ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism ; Biological Availability ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System/*metabolism ; Diarrhea/*enzymology ; Feces/chemistry ; Female ; Humans ; Immunosuppressive Agents/*pharmacokinetics/therapeutic use ; Intestines/*enzymology ; *Kidney Transplantation ; Liver/*enzymology ; Male ; Middle Aged ; Postoperative Period ; Prospective Studies ; Tacrolimus/*pharmacokinetics/therapeutic use ; }, abstract = {Renal transplant recipients suffering from persistent diarrhea have been repeatedly reported to have increased tacrolimus (Tac) trough levels. This study aimed to explore this phenomenon in detail in 15 renal transplant recipients with diarrhea, whose immunosuppression consisted of corticosteroids, mofetil mycophenolate and Tac. Both hepatic and intestinal CYP3A4 and PGP activity, important determinants of Tac bioavailability, were assessed, together with global CYP activity and investigations for gastrointestinal infection, function and morphology. Global CYP, CYP3A4, PGP and trough/dose levels of Tac were compared with diarrhea-free controls. In addition, a pharmacokinetic study of Tac was performed in 11 patients affected by diarrhea versus 9 controls. As expected, diarrhea was associated with increased Tac trough levels. An even stronger, significant increase of dose-normalized Tac levels was observed between 90 and 360 min after Tac intake. Time to peak concentration and drug half-life, however, were not altered. In addition, a concomitant decrease (+/-50%) of intestinal PGP activity was noticed in patients with diarrhea. For global CYP, CYP3A4 and hepatic PGP activity no such differences were noted. This pattern was not influenced by the specific cause of diarrhea. These data strongly suggest that persistent diarrhea is associated with an increased oral bioavailability of Tac.}, }
@article {pmid15870303, year = {2005}, author = {Johannessen, GS and Bengtsson, GB and Heier, BT and Bredholt, S and Wasteson, Y and Rørvik, LM}, title = {Potential uptake of Escherichia coli O157:H7 from organic manure into crisphead lettuce.}, journal = {Applied and environmental microbiology}, volume = {71}, number = {5}, pages = {2221-2225}, pmid = {15870303}, issn = {0099-2240}, mesh = {Animals ; Cattle ; Escherichia coli O157/*isolation &amp; purification ; Feces/microbiology ; Lactuca/*microbiology ; Manure/*microbiology ; }, abstract = {To investigate the potential transfer of Escherichia coli O157:H7 from contaminated manure to fresh produce, lettuce seedlings were transplanted into soil fertilized with bovine manure which had been inoculated with approximately 10(4) CFU g(-1) E. coli O157:H7. The lettuce was grown for approximately 50 days in beds in climate-controlled rooms in a greenhouse. As the bacterium was not detected in the edible parts of the lettuce, the outer leaves of the lettuce, or the lettuce roots at harvest it was concluded that transmission of E. coli O157:H7 from contaminated soil to lettuce did not occur. The pathogen persisted in the soil for at least 8 weeks after fertilizing but was not detected after 12 weeks. Indigenous E. coli was detected only sporadically on the lettuce at harvest, and enterococci were not detected at all. The numbers of enterococci declined more rapidly than those of E. coli in the soil. Pseudomonas fluorescens, which inhibited growth of E. coli O157:H7 in vitro, was isolated from the rhizosphere.}, }
@article {pmid15868586, year = {2005}, author = {Wildhaber, BE and Teitelbaum, DH and Coran, AG}, title = {Total colonic Hirschsprung's disease: a 28-year experience.}, journal = {Journal of pediatric surgery}, volume = {40}, number = {1}, pages = {203-6; discussion 206-7}, doi = {10.1016/j.jpedsurg.2004.09.033}, pmid = {15868586}, issn = {1531-5037}, mesh = {Anastomosis, Surgical ; Anus Diseases/etiology ; Constriction, Pathologic ; Digestive System Surgical Procedures/*adverse effects ; Enterocolitis/etiology ; Fecal Incontinence/etiology ; Female ; Follow-Up Studies ; Hirschsprung Disease/*surgery ; Humans ; Infant ; Infant, Newborn ; Male ; Perineum ; Postoperative Complications ; Recovery of Function ; Retrospective Studies ; Skin Diseases/etiology ; Treatment Outcome ; }, abstract = {PURPOSE: The aim of this study was to review outcomes after surgical treatment of total colonic Hirschsprung's disease (TCH).<br><br>METHODS: Twenty-five records of patients with TCH treated between 1974 and 2002 were reviewed. Follow-up data were collected using a standardized questionnaire. Objective functional outcome was assessed using a scoring system.<br><br>RESULTS: Twenty patients had aganglionosis of the colon and distal ileum, 5 of whom had a more extensive condition. One of these 5 patients underwent an endorectal pull-through (ERPT), 1 underwent intestinal transplantation, and 3 died. Four of the remaining 20 patients underwent a primary ERPT, 16 received a stoma as neonates followed by ERPT in 12, and a Martin-Duhamel procedure or Swenson's operation in 3 (median age, 10.5 months); 1 remains with an ostomy. Postoperative complications included enterocolitis (55%), anal stricture (25%), and perineal excoriation (20%). Mean follow-up were 17.5 years (+/-11.1 years). Eighty-nine percent were free of recurrent enterocolitis. Frequency of bowel movements is 1 to 5 per day in 82% of the patients, 18% have 6 or more bowel movements per day. Occasional soiling is noted in 40% (one third of those requiring nighttime diapers). Overall functional outcome was good in 83%. Those patients with the longest follow-up periods had the best stooling scores (P = .04).<br><br>CONCLUSIONS: Surgical treatment of TCH is associated with a number of complications including recurrent enterocolitis and anal strictures. Long-term outcome is quite favorable.}, }
@article {pmid15868495, year = {2005}, author = {Hetzer, FH and Hahnloser, D and Knoblauch, Y and Löhlein, F and Demartines, N}, title = {New screening technique for sacral nerve stimulation under local anaesthesia.}, journal = {Techniques in coloproctology}, volume = {9}, number = {1}, pages = {25-28}, doi = {10.1007/s10151-005-0188-3}, pmid = {15868495}, issn = {1123-6337}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anesthesia, Local ; Electric Stimulation Therapy/*methods ; Electrodes, Implanted ; Fecal Incontinence/therapy ; Female ; Humans ; Male ; Manometry ; Middle Aged ; Rectum/innervation ; Sacrum/innervation ; Transcutaneous Electric Nerve Stimulation/*methods ; Urinary Incontinence/therapy ; }, abstract = {BACKGROUND: The purpose of this study was to assess the influence of the type of anaesthesia (local vs. general) and of the electrode used (test electrode vs. tined lead) on a successful screening period.<br><br>METHODS: Between May 2001 and January 2004, we performed 25 percutaneous nerve evaluation (PNE) tests in 20 patients (11 women). The first 15 PNE tests were followed by introducing a conventional electrode, and since 2003 by a tined lead electrode. Success was defined as reduction of symptoms by more than 50%.<br><br>RESULTS: A stimulator was implanted in 13 (68%) patients, including 4 of 14 screened with the conventional electrode and 9 of 10 screened with tined lead electrode (p=0.005). Eleven (44%) of the PNE tests were done under local anaesthesia, but the success rate was not influenced by the type of anaesthesia (local 46% vs. general 61%, p=0.682).<br><br>CONCLUSIONS: PNE testing and implantation of the tined lead electrode can be easily performed at the same time under local anaesthesia. The use of the new tined lead electrode significantly increased the success rate for the screening phase.}, }
@article {pmid15847259, year = {2005}, author = {Tran, MQ and Gohh, RY and Morrissey, PE and Dworkin, LD and Gautam, A and Monaco, AP and Yango, AF}, title = {Cryptosporidium infection in renal transplant patients.}, journal = {Clinical nephrology}, volume = {63}, number = {4}, pages = {305-309}, doi = {10.5414/cnp63305}, pmid = {15847259}, issn = {0301-0430}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Colon/microbiology ; Cryptosporidiosis/complications/drug therapy/*parasitology ; Cryptosporidium parvum/isolation &amp; purification ; Female ; Follow-Up Studies ; Humans ; Immunocompromised Host ; Kidney Failure, Chronic/complications/surgery ; *Kidney Transplantation ; Middle Aged ; }, abstract = {Cryptosporidium parvum, an intracellular protozoan parasite, is a significant cause of gastrointestinal disease worldwide. Transmission can occur from an infected person, animal or fecally contaminated environment. The clinical manifestations of cryptosporidiosis are dependent on the immunologic state of the host. Infection among immunocompetent hosts results in diarrhea that is typically self-limited. In immunocompromised hosts, however, the infection may be protracted and life-threatening with no reliable antimicrobial therapy. In transplant patients, a course of antimicrobial therapy along with concurrent reduction in immunosuppression optimize immunologic status and may potentially lead to resolution of the infection.}, }
@article {pmid15846442, year = {2005}, author = {Person, B and Wexner, SD}, title = {Advances in the surgical treatment of fecal incontinence.}, journal = {Surgical innovation}, volume = {12}, number = {1}, pages = {7-21}, doi = {10.1177/155335060501200103}, pmid = {15846442}, issn = {1553-3506}, mesh = {Anal Canal/physiopathology/surgery ; Electric Stimulation Therapy ; Electrocoagulation ; Fecal Incontinence/*therapy ; Glucans/therapeutic use ; Humans ; Lumbosacral Plexus/physiopathology ; Muscle, Skeletal/transplantation ; Prosthesis Implantation ; Radiofrequency Therapy ; Zirconium/therapeutic use ; }, abstract = {Although surgery for fecal incontinence has been shown to be effective, it is still very challenging and sometimes frustrating. Overlapping sphincteroplasty, by far the most common procedure, is effective in patients with sphincter defects; however, recent data suggest that success rates tend to deteriorate over time. A thorough preoperative evaluation incorporates numerous factors, including patient characteristics, severity of incontinence, type and size of the sphincter defect as assessed by physical examination, anal ultrasound, and anorectal physiology studies including anal manometry, electromyography, and pudendal nerve terminal motor latency assessment. The use of these evaluation methods has allowed better patient assignment for a variety of new alternative treatment options. Innovations in the surgical treatment of fecal incontinence range from simple, office-based sphincter augmentation techniques to surgical implantation of mechanical devices. This article reviews 5 alternative surgical treatment options for fecal incontinence: injection of carbon-coated beads in the submucosa of the anal canal, radiofrequency energy delivery, stimulated graciloplasty, artificial bowel sphincter, and sacral nerve stimulation.}, }
@article {pmid15825025, year = {2005}, author = {Walls, T and Hawrami, K and Ushiro-Lumb, I and Shingadia, D and Saha, V and Shankar, AG}, title = {Adenovirus infection after pediatric bone marrow transplantation: is treatment always necessary?.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {40}, number = {9}, pages = {1244-1249}, doi = {10.1086/429235}, pmid = {15825025}, issn = {1537-6591}, mesh = {Adenoviridae/isolation &amp; purification ; Adenoviridae Infections/blood/*drug therapy/*etiology ; Adolescent ; Antiviral Agents/therapeutic use ; Bone Marrow Transplantation/*adverse effects ; Child ; Child, Preschool ; Feces/virology ; Humans ; Retrospective Studies ; }, abstract = {BACKGROUND: Adenovirus infections are associated with significant rates of morbidity and mortality among children after bone marrow transplantation (BMT). Many transplantation units use molecular virological methods, such as polymerase chain reaction (PCR), for surveillance for adenovirus infection and give preemptive antiviral therapy to children with evidence of disseminated adenovirus infection. This treatment strategy has never been evaluated in clinical trials.<br><br>METHODS: We retrospectively tested blood samples obtained from a cohort of children who had undergone BMT before the introduction of regular weekly surveillance for adenovirus infection. A total of 273 samples collected from 26 patients between May 1998 and June 2002 were tested for adenovirus infection by quantitative PCR. Virus load was quantified for each sample yielding positive test results, and the clinical notes and virological records of each child were reviewed.<br><br>RESULTS: Evidence of adenovirus infection was found in 11 children (42%), 7 of whom had not previously had positive test results. Receipt of T cell-depleted transplants was associated with a significantly higher incidence of adenovirus infection during the posttransplantation period. The 2 children who died from adenovirus disease developed infection within 2 weeks after transplantation, and both had very low absolute lymphocyte counts at the time of diagnosis. Seven of 11 children with blood samples that were found to be positive for adenovirus by PCR cleared the virus without antiviral therapy.<br><br>CONCLUSIONS: Surveillance for adenovirus by PCR is better than symptomatic testing for detecting adenovirus infection. Antiviral therapy may not be necessary for all children who develop adenovirus viremia after BMT.}, }
@article {pmid15740563, year = {2005}, author = {Smith, AD and Bai, D and Marroquin, CE and Tuttle-Newhall, JE and Desai, DM and Collins, BH and Muir, A and Kuo, PC and McHutchison, J and Rockey, DC}, title = {Gastrointestinal hemorrhage due to complicated gastroduodenal ulcer disease in liver transplant patients taking sirolimus.}, journal = {Clinical transplantation}, volume = {19}, number = {2}, pages = {250-254}, doi = {10.1111/j.1399-0012.2005.00332.x}, pmid = {15740563}, issn = {0902-0063}, mesh = {Adult ; Drug Monitoring ; Duodenal Ulcer/*chemically induced ; Female ; Follow-Up Studies ; Hematemesis/chemically induced ; Humans ; Immunosuppressive Agents/*adverse effects ; *Liver Transplantation ; Male ; Melena/chemically induced ; Middle Aged ; Peptic Ulcer Hemorrhage/*chemically induced ; Sirolimus/*adverse effects ; Stomach Ulcer/*chemically induced ; Wound Healing/drug effects ; }, abstract = {Sirolimus is emerging as a popular immunosuppressive agent for patients undergoing solid organ and pancreatic cell transplantation. Here, we report the clinical courses of three patients receiving sirolimus who developed aggressive gastroduodenal ulcer disease. One patient died from massive gastrointestinal bleeding, and ulcers in the other two patients healed only after discontinuation of sirolimus. We propose that the mechanism underlying this severe ulcer diathesis, and poor ulcer healing, was linked to the well-known inhibitory effects of sirolimus on wound healing. We propose that sirolimus should be used carefully (or even withheld) in patients with known or previous ulcer disease, and further that it should be used prudently and/or in conjunction with aggressive prophylaxis therapy in those at risk for ulcer disease.}, }
@article {pmid15720361, year = {2005}, author = {Hossack, T and Solomon, MJ and Young, JM}, title = {Ano-cutaneous flap repair for complex and recurrent supra-sphincteric anal fistula.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {7}, number = {2}, pages = {187-192}, doi = {10.1111/j.1463-1318.2004.00745.x}, pmid = {15720361}, issn = {1462-8910}, mesh = {Adult ; Aged ; Anal Canal/*surgery ; Fecal Incontinence/etiology ; Female ; Humans ; Male ; Middle Aged ; Quality of Life ; Rectal Fistula/*surgery ; Recurrence ; Skin Transplantation ; *Surgical Flaps ; Treatment Outcome ; Wound Healing ; }, abstract = {BACKGROUND: Suprasphincteric fistulae remain the most difficult to cure.<br><br>OBJECTIVES: The purpose of this study was to evaluate the healing rate of suprasphincteric anal fistula treated by ano-cutaneous advancement flap repair, and the impact of this procedure on continence and quality of life.<br><br>METHOD: Sixteen patients with complex, recurrent or chronic suprasphincteric fistulae associated with significant tissue damage (necrotizing fasciitis, keyhole deformity and anal stenosis) or who had failed previous surgical procedures were treated by ano-cutaneous flap closure. They were assessed pre and postoperatively by the treating surgeon for wound healing and fistula recurrence and later followed up by phone interview using the St Mark's Hospital incontinence score and the Perianal Disease Activity Index (PDAI) as indicators of treatment outcome.<br><br>RESULTS: Fifteen patients had successful healing of their fistula with the cutaneous flap, with recurrence in only one. The most common short-term complications were minor graft site wound separation, which healed in all cases without intervention, and wound pain, which settled over time and was not associated with recurrence. Continence improved for almost 70% of the patients, with a significant reduction in St Mark's incontinence scores (t = 2.62, 15 d.f., P = 0.02). PDAI also decreased significantly (t = 7.55, 15 d.f., P < 0.001), demonstrating improvement in quality of life for most patients.<br><br>CONCLUSION: Ano-cutaneous flap can achieve healing of complex and recurrent suprasphincteric anal fistula in patients who had previously failed at other forms of treatment thus improving their quality of life and continence.}, }
@article {pmid19521522, year = {2005}, author = {Luo, Y and Higa, M and Amae, S and Yambe, T and Okuyama, T and Takagi, T and Matsuki, H}, title = {The possibility of muscle tissue reconstruction using shape memory alloys.}, journal = {Organogenesis}, volume = {2}, number = {1}, pages = {2-5}, pmid = {19521522}, issn = {1547-6278}, abstract = {Severe dysfunction of muscle tissues can be treated by transplantation but the success rate is still not high enough. One possibility instead is to replace the dysfunctional muscle with artificial muscles. This article introduces a unique approach using shape memory alloys (SMAs) to replace the anal sphincter muscle for solving the problem of fecal incontinence. The use of SMAs that exhibit a two-way shape memory effect allows the device to function like a sphincter muscle and facilitates simple design. In this article, we will give a brief introduction to the functional material-SMA-together with its medical applications, and will follow this with a description of the recent progress in research and development of an SMA-based artificial sphincter. The possibility of its commercialization will also be discussed.}, }
@article {pmid15616352, year = {2004}, author = {Knott, NA and Davis, AR and Buttemer, WA}, title = {Passive flow through an unstalked intertidal ascidian: orientation and morphology enhance suspension feeding in Pyura stolonifera.}, journal = {The Biological bulletin}, volume = {207}, number = {3}, pages = {217-224}, doi = {10.2307/1543210}, pmid = {15616352}, issn = {0006-3185}, mesh = {Analysis of Variance ; Animals ; Environment ; Feces ; Feeding Behavior/*physiology ; New South Wales ; Orientation/*physiology ; Urochordata/*anatomy &amp; histology/*physiology ; *Water Movements ; }, abstract = {Passive flow is believed to increase the gains and reduce the costs of active suspension feeding. We used a mixture of field and laboratory experiments to evaluate whether the unstalked intertidal ascidian Pyura stolonifera exploits passive flow. We predicted that its orientation to prevailing currents and the arrangement of its siphons would induce passive flow due to dynamic pressure at the inhalant siphon, as well as by the Bernoulli effect or viscous entrainment associated with different fluid velocities at each siphon, or by both mechanisms. The orientation of P. stolonifera at several locations along the Sydney-Illawarra coast (Australia) covering a wide range of wave exposures was nonrandom and revealed that the ascidians were consistently oriented with their inhalant siphons directed into the waves or backwash. Flume experiments using wax models demonstrated that the arrangement of the siphons could induce passive flow and that passive flow was greatest when the inhalant siphon was oriented into the flow. Field experiments using transplanted animals confirmed that such an orientation resulted in ascidians gaining food at greater rates, as measured by fecal production, than when oriented perpendicular to the wave direction. We conclude that P. stolonifera enhances suspension feeding by inducing passive flow and is, therefore, a facultatively active suspension feeder. Furthermore, we argue that it is likely that many other active suspension feeders utilize passive flow and, therefore, measurements of their clearance rates should be made under appropriate conditions of flow to gain ecologically relevant results.}, }
@article {pmid15610083, year = {2004}, author = {López, T and Quesada, M and Almirall, J and Sanfeliu, I and Segura, F and Calvet, X}, title = {Usefulness of non-invasive tests for diagnosing Helicobacter pylori infection in patients undergoing dialysis for chronic renal failure.}, journal = {Helicobacter}, volume = {9}, number = {6}, pages = {674-680}, doi = {10.1111/j.1083-4389.2004.00282.x}, pmid = {15610083}, issn = {1083-4389}, mesh = {Aged ; Antigens, Bacterial/analysis ; Breath Tests ; Enzyme-Linked Immunosorbent Assay ; Feces/microbiology ; Female ; Helicobacter Infections/complications/*diagnosis ; *Helicobacter pylori ; Humans ; Kidney Failure, Chronic/*complications ; Male ; Middle Aged ; Predictive Value of Tests ; Reference Standards ; Reproducibility of Results ; Sensitivity and Specificity ; Urease/analysis ; }, abstract = {BACKGROUND: Helicobacter pylori infection in chronic renal failure patients has been linked to peptic ulcer and gastric neoplasia after kidney transplantation. It may also contribute to the accelerated arteriosclerosis that is usual in this population. Few data are available on the usefulness of noninvasive diagnostic tests for H. pylori infection in dialyzed patients, especially regarding the new fecal antigen detection tests. The objective of this study was to determine the efficacy of a noninvasive test for H. pylori infection in patients with chronic renal failure.<br><br>METHODS: Eighty-six patients were included in a cross-sectional study. Urea breath test, serology and three fecal tests--FemtoLab H. pylori (Connex, Germany), Premier Platinum HpSA (Meridian, USA) and Simple H. pylori (Operon SA, Spain) were performed. Helicobacter pylori status was determined by concordance of the tests. Sensitivity, specificity and positive and negative predictive values were calculated for each test.<br><br>RESULTS: Sensitivity, specificity, positive and negative predictive values were 94%, 96%, 94% and 96% for the urea breath test; 97%, 64%, 66% and 97% for serology; 86%, 100%, 100% and 91%, for FemtoLab H. pylori; 58%, 96%, 91% and 76% for Premier Platinum HpSA and 61%, 78%, 74% and 67% for Simple H. pylori.<br><br>CONCLUSIONS: The urea breath test seems to be the most reliable diagnostic method for H. pylori infection in patients with chronic renal failure. Serology has a low specificity, and the results of the fecal tests vary widely.}, }
@article {pmid15582124, year = {2004}, author = {Lamireau, T and Monnereau, S and Martin, S and Marcotte, JE and Winnock, M and Alvarez, F}, title = {Epidemiology of liver disease in cystic fibrosis: a longitudinal study.}, journal = {Journal of hepatology}, volume = {41}, number = {6}, pages = {920-925}, doi = {10.1016/j.jhep.2004.08.006}, pmid = {15582124}, issn = {0168-8278}, mesh = {Adolescent ; Age Distribution ; Child ; Child, Preschool ; Cohort Studies ; Cystic Fibrosis/*complications ; Disease Progression ; Exocrine Pancreatic Insufficiency/complications ; Female ; Humans ; Ileus/complications ; Incidence ; Infant ; Liver Diseases/*epidemiology/*etiology/physiopathology ; Longitudinal Studies ; Male ; Meconium ; Prevalence ; Prognosis ; Survival Analysis ; }, abstract = {BACKGROUND/AIMS: To describe the prevalence of liver disease in a cohort of 241 cystic fibrosis (CF) patients.<br><br>METHODS: 241 CF patients were followed-up every 3 months with clinical and biological assessment, and every year with ultrasonography of the liver. The presence of liver disease was studied using a multivariate Cox's regression analysis including variables such as history of meconium ileus, pulmonary function, pancreatic insufficiency and CFTR gene mutations.<br><br>RESULTS: The prevalence of liver disease was 18, 29, and 41% after 2, 5 and 12 years, respectively, and did not increase thereafter. In multivariate analysis, the probability of liver disease was independently associated with history of meconium ileus (P = 0.001) and pancreatic insufficiency (P = 0.004). CFTR mutations and severity of pulmonary disease were not associated with liver disease. Cirrhosis occurred in 19 (7.8%) patients at a median age of 10 years, and liver transplantation was required in five patients.<br><br>CONCLUSIONS: This study shows that CF related-liver disease occurs mainly in the first decade of life with a prevalence of 41% of patients at 12 years of age. A history of meconium ileus and pancreatic insufficiency are predictive of liver disease. Preventive treatment with ursodesoxycholic acid could be considered in patients with meconium ileus.}, }
@article {pmid15553438, year = {2004}, author = {Romano, G and Cocchiara, G and Calderone, F and Luna, E and Virzì, C and Agrusa, A and Romano, G and Buscemi, S and Di Bernardo, C and Buscemi, G and Maresi, E and Gioe', FP and Diana, G}, title = {[Endoscopic treatment of colorectal polyps in a digestive endoscopy outpatient department].}, journal = {Chirurgia italiana}, volume = {56}, number = {5}, pages = {669-673}, pmid = {15553438}, issn = {0009-4773}, mesh = {*Ambulatory Surgical Procedures ; Colonic Polyps/*surgery ; *Colonoscopy ; Colorectal Neoplasms/*surgery ; Female ; Humans ; Intestinal Polyps/surgery ; Male ; Middle Aged ; }, abstract = {The aim of this report was to evaluate the effectiveness of the endoscopic treatment of colonic polyps to allow secondary prophylaxis in order to prevent the onset of cancer arising from adenomas. From October 2002 to January 2004 we performed 487 colonoscopies on a patient group with the following indications: screening prior to kidney transplant; screening for colorectal cancer (patients positive at faecal occult blood testing); follow-up of patients who had undergone colonic resections for colorectal cancer; patients with other diseases. Colorectal polyps were diagnosed in 15 males and 15 females, with a mean age of 63 years. All the neoplasms were resected during colonoscopy and specimens sent for histological study. The histological examinations yielded the following results: 4 hyperplastic polyps; 9 tubular adenomas (6 with mild, 2 with mild-to-moderate, and 1 with severe dysplasia); 8 tubulo-villous adenomas (3 with mild, 1 with mild-to-moderate, and 4 with moderate dysplasia); 4 villous adenomas (3 with mild and 1 with severe dysplasia); 1 adenocarcinoma; 1 inflammatory polyp; in 3 cases we were unable to retrieve the polyps after polypectomy. Colonoscopic detection of a neoplasm allows us to remove it and send to the pathology laboratory for definitive histological diagnosis. Moreover, snare polypectomy can be a radical treatment for dysplastic polyps without stromal axis and basal membrane infiltration. We therefore conclude that colonoscopy allows not only early diagnosis of colonic neoplasms, but also radical curative treatment in the early stages.}, }
@article {pmid15527710, year = {2004}, author = {Arguedas, MR and Fallon, MB}, title = {Hepatitis A.}, journal = {Current treatment options in gastroenterology}, volume = {7}, number = {6}, pages = {443-450}, pmid = {15527710}, issn = {1092-8472}, abstract = {Hepatitis A infection is typically transmitted by the fecal-oral route. Symptomatic infection is highly dependent on the age of the patient and usually follows a self-limited course. Once diagnosed, clinical and biochemical follow-up in the outpatient setting is generally appropriate. Treatment aims are to achieve symptomatic relief and to maintain adequate hydration and caloric intake. In patients with more severe disease, hospitalization may be needed to accomplish aggressive symptomatic therapy and close monitoring of liver function tests and mental status. Prompt evaluation for liver transplantation is appropriate in the rare case where fulminant liver failure develops. Given the absence of specific therapy for hepatitis A virus infection, the most important health care intervention is prevention of infection and/or transmission, which can be accomplished with the safe and effective use of immune globulin and commercially available vaccines.}, }
@article {pmid15521938, year = {2004}, author = {Thornton, MJ and Kennedy, ML and Lubowski, DZ and King, DW}, title = {Long-term follow-up of dynamic graciloplasty for faecal incontinence.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {6}, number = {6}, pages = {470-476}, doi = {10.1111/j.1463-1318.2004.00714.x}, pmid = {15521938}, issn = {1462-8910}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/*surgery ; Electric Stimulation ; Electrodes, Implanted ; Fecal Incontinence/diagnosis/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Middle Aged ; Muscle, Smooth/*transplantation ; Patient Satisfaction ; Postoperative Complications ; *Quality of Life ; Plastic Surgery Procedures/methods ; Retrospective Studies ; Risk Assessment ; Severity of Illness Index ; Time Factors ; Treatment Outcome ; }, abstract = {OBJECTIVE: This paper presents the long-term morbidity, function and quality of life data for patients who have undergone dynamic graciloplasty (DGP) for faecal incontinence.<br><br>PATIENTS AND METHODS: All patients (n = 38) who had undergone DGP at one institution between 1993 and 2003 are presented. Thirty-three were available for long-term follow-up (median 60 months) and completed a telephone questionnaire assessing quality of life (QOL), bowel and sexual function and patient satisfaction. All patients had interval anorectal physiology studies.<br><br>RESULTS: At a median follow-up of 5 years, 72% had pain, swelling or paraesthesia in the donor leg and 27% had sexual dysfunction. Sixteen percent of patients had been converted to an end-colostomy for persisting incontinence and 11% for obstructed defaecation. All other patients have a normally functioning graciloplasty. Sixteen percent of patients reported a faecal continence score < 12. Of those patients with a functioning graciloplasty, 50% had obstructed defaecation and 64% reported that their bowel dysfunction had a negative impacted on their QOL. Age, medical comorbidity and anal manometry did not correlate with functional outcome. Quality of life scores and patient satisfaction scores correlated significantly with continence scores. There was a trend toward higher QOL and satisfaction scores with conversion to colostomy compared with a continence score > 12. Sixty percent of patients rated their satisfaction with DGP as 50% or better on a visual analogue scale, and this correlated strongly with the continence score at the time of the assessment (P < 0.001).<br><br>CONCLUSION: Dynamic graciloplasty significantly improves patient quality of life and anal continence for some patients. Despite increased experience, morbidity remains high and long-term continence scores are poor in a majority of cases. Obstructed defaecation is a significant problem after graciloplasty and antegrade colonic enemas may be needed. Significant prognostic factors for obstructed defaecation remain to be identified. The mechanism of both continence failure and surgical morbidity remains poorly defined in many patients and requires further investigation. The individual patient can expect a 16% chance of normal faecal continence at 5 years, with at least one surgical morbidity as a result of the procedure.}, }
@article {pmid15516438, year = {2004}, author = {Moore, RD and Miklos, JR and Kohli, N}, title = {Rectovaginal fistula repair using a porcine dermal graft.}, journal = {Obstetrics and gynecology}, volume = {104}, number = {5 Pt 2}, pages = {1165-1167}, doi = {10.1097/01.AOG.0000128116.52051.10}, pmid = {15516438}, issn = {0029-7844}, mesh = {Adult ; Animals ; Fecal Incontinence/diagnosis/etiology ; Female ; Follow-Up Studies ; Humans ; Patient Satisfaction ; Plastic Surgery Procedures/*methods ; Rectovaginal Fistula/*diagnosis/*surgery ; Risk Assessment ; Severity of Illness Index ; Skin Transplantation/*methods ; Swine ; Transplantation, Heterologous ; Treatment Outcome ; }, abstract = {BACKGROUND: Rectovaginal fistula repair is commonly performed through a vaginal route. In many cases, healthy tissue such as an autologous fat pad may be interposed between the suture lines and the vaginal epithelium to facilitate healing and prevent recurrence. We present a simple alternative to autologous flaps with the use of porcine dermal grafts in the repair of rectovaginal fistulae.<br><br>CASES: Two patients are presented with rectovaginal fistulae. In both cases the patients were found to have insufficient native tissue to achieve an adequate traditional multilayered closure, and therefore an acellular collagen porcine dermal graft was used as an interposition graft between the rectum and the vaginal epithelium in the repair.<br><br>CONCLUSION: Porcine dermal grafts may be a viable alternative to traditional autologous flaps or human dermal grafts for the repair of rectovaginal fistula.}, }
@article {pmid15492991, year = {2004}, author = {Morotti, RA and Kaufman, SS and Fishbein, TM and Chatterjee, NK and Fuschino, ME and Morse, DL and Magid, MS}, title = {Calicivirus infection in pediatric small intestine transplant recipients: pathological considerations.}, journal = {Human pathology}, volume = {35}, number = {10}, pages = {1236-1240}, doi = {10.1016/j.humpath.2004.06.013}, pmid = {15492991}, issn = {0046-8177}, mesh = {Apoptosis ; Biopsy ; Caliciviridae Infections/*diagnosis/pathology ; Child, Preschool ; DNA-Directed RNA Polymerases/genetics ; Diagnosis, Differential ; Diarrhea/virology ; Enteritis/*virology ; Feces/virology ; Graft Rejection/diagnosis ; Humans ; Infant ; Intestine, Small/*transplantation ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Human calicivirus (HuCV), a common cause of mild gastroenteritis in the general population, produces a prolonged diarrheal illness in pediatric recipients of small intestinal transplant (IT). By use of reverse-transcription polymerase chain reaction to detect the viral RNA polymerase gene in stool and tissue from gastrointestinal biopsies, 5 pediatric IT recipients with high-volume diarrhea were diagnosed with HuCV enteritis. Histopathologic findings of biopsies obtained at different gastrointestinal sites were studied retrospectively to identify characteristic features of HuCV enteritis and to distinguish these changes from rejection. Controls were 8 pediatric IT recipients with high-volume diarrhea but negative HuCV reverse-transcription polymerase chain reaction assays during the same time period. All HuCV biopsies showed increased mononuclear infiltrates in the lamina propria and villous blunting. Reactive disarray of surface epithelial cells and increased apoptosis in the surface epithelium and superficial lamina propria were characteristic features (in 4/5 patients). Increased glandular apoptosis was also present in 3/5 patients. Findings were more pronounced in jejunal allograft than ileal allograft, and were present in both graft and native bowel. In comparison with the control group, the architectural changes, surface epithelial reactive changes, and superficial apoptosis were characteristic of HuCV enteritis, while the presence of glandular apoptosis was a feature shared with cases of mild acute cellular rejection HuCV may cause severe allograft dysfunction after pediatric IT. Calicivirus infection has clinical and histological features that overlap with allograft rejection. Knowledge of the characteristic histologic features of HuCV enteritis aids in differential diagnosis.}, }
@article {pmid15455363, year = {2004}, author = {Vorobiev, GI and Odaryuk, TS and Tsarkov, PV and Talalakin, AI and Rybakov, EG}, title = {Resection of the rectum and total excision of the internal anal sphincter with smooth muscle plasty and colonic pouch for treatment of ultralow rectal carcinoma.}, journal = {The British journal of surgery}, volume = {91}, number = {11}, pages = {1506-1512}, doi = {10.1002/bjs.4330}, pmid = {15455363}, issn = {0007-1323}, mesh = {Adult ; Aged ; *Artificial Organs ; *Colonic Pouches ; Fecal Incontinence/*etiology/physiopathology ; Female ; Follow-Up Studies ; Humans ; Length of Stay ; Male ; Middle Aged ; Muscle, Smooth/*transplantation ; Postoperative Complications/*etiology/physiopathology ; Pressure ; Rectal Neoplasms/physiopathology/*surgery ; *Surgical Flaps ; Treatment Outcome ; }, abstract = {BACKGROUND: Intersphincteric resection can provide tumour-free margins for rectal tumours located 0-1 cm above the dentate line. However, the internal anal sphincter (IAS) is partially or totally resected and some degree of anal incontinence may develop. A novel technique of smooth muscle plasty of the IAS and colonic pouch construction is described, along with an assessment of morbidity, oncological results and functional outcome.<br><br>PATIENTS AND METHODS: Between 1997 and 2002, 27 patients (16 men; median age 55 (range 26-75) years) were operated on for T2-3 N0-1 M0 rectal carcinoma located a median of 1.0 (range 0.5-1.5) cm from the dentate line. Resection of the IAS was performed transanally. A smooth muscle cuff, fashioned from the muscular layer of colon, and a colonic pouch were used for anorectal reconstruction.<br><br>RESULTS: There were no perioperative deaths. Anastomotic leakage developed in two patients. After a median follow-up of 38 (range 14-66) months no local recurrence was detected. Distant metastases occurred in three patients, two of whom died. Perfect functional outcome was achieved in 22 of 26 patients. At 6 months after surgery the mean(s.d.) resting anal pressure was 49(8) mmHg.<br><br>CONCLUSION: In selected patients intersphincteric resection does not compromise the oncological result. The suggested anorectal reconstruction may improve the functional outcome.}, }
@article {pmid15376181, year = {2004}, author = {Altomare, DF and Binda, GA and Dodi, G and La Torre, F and Romano, G and Rinaldi, M and Melega, E}, title = {Disappointing long-term results of the artificial anal sphincter for faecal incontinence.}, journal = {The British journal of surgery}, volume = {91}, number = {10}, pages = {1352-1353}, doi = {10.1002/bjs.4600}, pmid = {15376181}, issn = {0007-1323}, mesh = {Device Removal ; Fecal Incontinence/*surgery ; Humans ; Manometry ; Patient Satisfaction ; *Prostheses and Implants/*standards ; Treatment Failure ; }, }
@article {pmid15373636, year = {1999}, author = {Gustavsson, ML and Oriol, R and Samuelsson, BE and Henry, SM}, title = {Leb glycolipids present in the lumen of the gastrointestinal tract of rats do not enter the plasma compartment.}, journal = {Immunohematology}, volume = {15}, number = {4}, pages = {150-158}, pmid = {15373636}, issn = {0894-203X}, abstract = {We orally administered to rats several times more Leb glycolipids than is proportionally found in the gastrointestinal tract of humans. This was done in an effort to study two potential phenomena: the possibility that glycolipids in plasma may originate from glycolipids derived from the lumen of the gastrointestinal tract, and to investigate the potential to secondarily modify in vivo the glycolipid profile of gastrointestinal tract epithelial cells, a phenomenon clearly established for human erythrocytes, leukocytes, and platelets. We were able to establish that some of the orally administered glycolipids can be detected at the surface of the upper region mucosa of the gastrointestinal tract for more than 24 hours and are essentially excreted intact in stools in less than 72 hours. Some fecal degradation of the Leb glycolipids into Lea and H type 1 did occur. Although we clearly established that the glycolipids were present in the mucus layer adherent to the cell surface, we could not conclusively establish if the glycolipids had inserted into the epithelial cell membrane. This, however, could not be excluded. The fact that the fed glycolipids remained in the mucus layer of the upper region of the gastrointestinal tract for at least 24 hours may have some pharmacological value. Using sensitive techniques, including red cell serology, immunohistology, and immunochemistry of glycolipids isolated from plasma and red cells, there was no evidence that the fed Leb glycolipids reached the plasma compartment, thus suggesting that glycolipids present in the lumen of the gastrointestinal tract cannot reach the circulation.}, }
@article {pmid15322839, year = {2004}, author = {Pakarinen, MP and Lauronen, J and Pirinen, P and Kuusanmäki, P and Raivio, P and Halttunen, J}, title = {Octreotide in the treatment of small intestinal dysfunction after a model of jejunoileal autotransplantation in the pig.}, journal = {Pediatric surgery international}, volume = {20}, number = {10}, pages = {791-796}, pmid = {15322839}, issn = {0179-0358}, mesh = {Animals ; Autonomic Denervation ; Bile Acids and Salts/pharmacokinetics ; Cell Proliferation ; Cholesterol/analogs &amp; derivatives/blood/pharmacokinetics ; Disease Models, Animal ; Feces/chemistry ; Female ; Gastrointestinal Agents/*therapeutic use ; Gastrointestinal Transit/drug effects ; Ileum/pathology/*transplantation ; Intestinal Absorption/drug effects ; Intestinal Mucosa/pathology ; Ischemia ; Jejunum/pathology/*transplantation ; Lymph Nodes/surgery ; Mesenteric Artery, Superior/surgery ; Octreotide/*therapeutic use ; Random Allocation ; Swine ; Time Factors ; Transplantation, Autologous ; Weight Gain ; }, abstract = {Enteric denervation and ischemic injury contribute to dysmotility and malabsorption following intestinal transplantation. We hypothesized that, by prolonging bowel transit and by ameliorating dysmotility, octreotide (OT) may improve cholesterol and bile acid absorption after jejunoileal autotransplantation. Seventeen pigs with fixed food intake underwent either jejunal transection (n = 6), or jejunoileal autotransplantation, which includes extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia (n = 11). Five randomly chosen autotransplanted animals received intramuscular long-acting OT (10 mg) once a month. After 8 weeks, weight gain, intestinal transit time, fecal excretion of bile acids and cholesterol, and fractional cholesterol absorption were determined. Jejunal and ileal specimens were collected for histochemical analyses. Plasma cholestenol and campesterol, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks. Following jejunoileal autotransplantation, octreotide treatment significantly increased the median intestinal transit time from 22.8 to 24.8 h and the median body weight gain from 166 to 187%. Jejunoileal autotransplantation significantly increased fecal bile acid excretion, plasma cholestenol, and bacterially modified fecal neutral sterols, and decreased absorption of cholesterol, plasma campesterol, and biliary cholesterol secretion. These changes were not significantly modified by OT treatment. Bowel wall and mucosal structure, mucosal proliferation, and weight or microvilli showed no statistically significant differences between autotransplanted animals with or without OT treatment. Findings of the present study suggest that octreotide prolongs intestinal transit time and improves weight gain after jejunoileal autotransplantation, but has no effect on malabsorption of cholesterol and bile acids.}, }
@article {pmid15300531, year = {2004}, author = {Pakarinen, MP and Pirinen, P and Lauronen, J and Raivio, P and Kuusanmäki, P and Halttunen, J}, title = {Growth hormone selectively improves intestinal cholesterol absorption after jejunoileal autotransplantation in pigs.}, journal = {Journal of pediatric surgery}, volume = {39}, number = {8}, pages = {1220-1225}, doi = {10.1016/j.jpedsurg.2004.04.017}, pmid = {15300531}, issn = {1531-5037}, mesh = {Animals ; Autonomic Denervation ; Bile Acids and Salts/metabolism ; Cholesterol/*analogs &amp; derivatives/biosynthesis/*pharmacokinetics ; Cholesterol, Dietary/*pharmacokinetics ; Drug Evaluation, Preclinical ; Feces/chemistry ; Female ; Human Growth Hormone/pharmacology/*therapeutic use ; Ileum/*transplantation ; Intestinal Absorption/*drug effects ; Intestinal Mucosa/enzymology/ultrastructure ; Jejunum/*transplantation ; Laparotomy ; Lipids/blood ; Malabsorption Syndromes/blood/*drug therapy/etiology ; Phytosterols/*pharmacokinetics ; Postoperative Complications/blood/*drug therapy ; Recombinant Proteins/pharmacology/therapeutic use ; Sitosterols/*pharmacokinetics ; Sus scrofa ; Transplantation, Autologous ; }, abstract = {BACKGROUND/PURPOSE: Small bowel transplantation impairs enteric function and causes malabsorption of cholesterol and bile acids. Growth hormone stimulates intestinal absorptive function. The authors hypothesized that long-term growth hormone therapy could improve absorption of bile acids and cholesterol after autotransplantation of the jejunoileum.<br><br>METHODS: Sixteen pigs with similar food, cholesterol, and fat intake underwent either sham laparotomy or a model of jejunoileal autotransplantation, including extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia. Five randomly chosen autotransplanted animals received daily growth hormone treatment for 8 weeks. Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Mucosal morphometrics, proliferation, and enzyme activities were determined. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks.<br><br>RESULTS: After jejunoileal autotransplantation, growth hormone treatment significantly increased body weight gain, cholesterol absorption efficiency from 45.1% to 62.1%, plasma campesterol to cholesterol proportions, and biliary secretion of cholesterol. With or without growth hormone treatment, autotransplantation significantly increased fecal bile acid excretion, plasma cholesterol precursors, fecal bacterially modified neutral sterols, mucosal thickness of the ileum (but not jejunum), and intestinal transit time when compared with sham-operated animals. Crypt cell proliferation, mucosal enzyme activities, and microvilli showed no differences between the groups.<br><br>CONCLUSIONS: These findings suggest that growth hormone treatment selectively improves cholesterol, but not bile acid absorption, after autotransplantation of the jejunoileum.}, }
@article {pmid15293901, year = {2004}, author = {Ercis, S and Ergin, A and Hasçelik, G}, title = {[Six years evaluation of Clostridium difficile associated diarrhea].}, journal = {Mikrobiyoloji bulteni}, volume = {38}, number = {1-2}, pages = {45-50}, pmid = {15293901}, issn = {0374-9096}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/adverse effects ; Bacterial Proteins/*analysis ; Bacterial Toxins/*analysis ; Child ; Child, Preschool ; Clostridioides difficile/*pathogenicity ; Diarrhea/diagnosis/*microbiology ; Enterocolitis, Pseudomembranous/complications/diagnosis/*microbiology ; Enterotoxins/*analysis ; Feces/chemistry ; Female ; Humans ; Immunoenzyme Techniques ; Infant ; Kidney Failure, Chronic/complications ; Male ; Middle Aged ; Neoplasms/complications ; Pulmonary Disease, Chronic Obstructive/complications ; Risk Factors ; }, abstract = {This study was aimed to detect the presence of Clostridium difficile toxin in the stool samples of patients with antibiotic-associated diarrhea or pseudomembranous colitis, and to relate its presence with the clinical findings of the patients. Between January 1997-April 2003, a total of 726 stool samples were investigated for C. difficile toxin A and/or B by enzyme immunoassay. Of them, 68 (9.4%) were found positive for C. difficile toxin (62 were toxin A, 6 were toxin B). C. difficile associated diarrhea were found to be related mostly with the use of beta-lactam/beta-lactamase inhibitor combinations (32/68), followed by aminoglycosides (12/68), and cephalosporins (8/68). The ages of the patients were between 1-86 years old (mean: 43.3 years), and 36 (52.9%) of them had an underlying conditions. Chronic obstructive pulmonary disease and chronic renal failure were the underlying disease in 18, malignancy in 11, and others (diabetes, hepatitis, transplantation, multiple sclerosis) in 7 of the patients. In conclusion, toxin detection and knowledge of the risk factors are the beneficial guidelines for the diagnosis of C. difficile associated diarrhea in the routine setting.}, }
@article {pmid15261189, year = {2004}, author = {Schaeffer, MW and Buell, JF and Gupta, M and Conway, GD and Akhter, SA and Wagoner, LE}, title = {Strongyloides hyperinfection syndrome after heart transplantation: case report and review of the literature.}, journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, volume = {23}, number = {7}, pages = {905-911}, doi = {10.1016/j.healun.2003.06.008}, pmid = {15261189}, issn = {1053-2498}, mesh = {Bronchoalveolar Lavage Fluid/parasitology ; Fatal Outcome ; Feces/parasitology ; Graft Rejection/prevention &amp; control ; *Heart Transplantation/immunology ; Humans ; *Immunocompromised Host ; Male ; Middle Aged ; Postoperative Complications/*immunology ; Strongyloidiasis/*etiology/immunology/physiopathology ; Syndrome ; }, abstract = {Stronglyoides hyperinfection syndrome (SHS) is an augmentation of the infective life cycle of S stercoralis. Immunosuppressed patients, especially those taking corticosteroid therapy, are at risk. We present a case of fatal SHS with disseminated infection following orthotopic heart transplantation. The patient was treated with increased doses of immunosuppressive medications for graft rejection, including corticosteroids. A review of the literature describing the pathophysiology, host defenses and treatment of SHS is also presented. Diagnostic tests for S stercoralis are reviewed. SHS should be part of the differential diagnosis in immunosuppressed patients presenting with sepsis or gastrointestinal or pulmonary complaints. Pretransplant evaluation for parasitic infections, including strongyloidiasis, should occur in endemic areas or in patients at risk for occult infestation.}, }
@article {pmid15255347, year = {2004}, author = {Abbassi, MS and Achour, W and Ben Hassen, A}, title = {[Characteristics of Enterococcus strains isolated from neutropenic patients at the National Bone-Marrow Transplantation Center of Tunis].}, journal = {Bulletin de la Societe de pathologie exotique (1990)}, volume = {97}, number = {2}, pages = {91-94}, pmid = {15255347}, issn = {0037-9085}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/therapeutic use ; Bone Marrow Transplantation/*adverse effects ; Colony Count, Microbial ; DNA, Bacterial/analysis/genetics ; Drug Resistance, Multiple, Bacterial ; *Enterococcus/classification/genetics/immunology ; Feces/microbiology ; Female ; Gastrointestinal Diseases/drug therapy/epidemiology/*etiology ; Gram-Positive Bacterial Infections/drug therapy/epidemiology/*etiology ; Humans ; Leukemia, Myeloid, Acute/complications/therapy ; Male ; Microbial Sensitivity Tests/methods ; Neutropenia/*complications ; Phenotype ; Population Surveillance ; Serotyping ; Time Factors ; Tunisia/epidemiology ; Urban Health/statistics &amp; numerical data ; }, abstract = {The frequency of digestive colonization of neutropenic patients by Enterococci during the phase of pre-transplant and post-transplant of bone marrow is important indeed as 441 Enterococcus spp strains have been isolated from stool-cultures and other specimens whithin a period of 35 months in 80 patients. A quantitative stool culture was done on appropriate media. Simple bile-esculine agar (BE) and bile esculine-agar additionned with 6 mg/l of vancomycine (BEV) were used for detecting Enterococci. These organisms were taken into account, when then numeration was > 10(3) UFC/g of fecal sample on BE and in all cases on BEV. Species isolated were essentially Enterococcus faecalis (39.4%), Enterococcus faecium (34.4%) and Enterococcus casseliflavus (17%). These strains were characterized by a high frequency of high-level resistance to gentamicin (40.8%). Resistance to amoxicillin concerns 40% of E. faecium strains. Seventeen multiresistant strains of E. faecium isolated from 7 patients (colonized during a long period and receiving a gut decontamination treatment) were the subject of a phenotypic analysis (biotyping, antibiotyping and determination of MICs to beta-lactam, aminoglycosides and glycopeptides). This analysis showed that these strains are distinguishable, endogenic and specific for each patient, the common multiresistance trait resulted from the selective pressure of decontamination treatment used for our patient.}, }
@article {pmid15253275, year = {2004}, author = {Wagner, AM and Loganbill, JK and Besselsen, DG}, title = {Detection of lactate dehydrogenase-elevating virus by use of a fluorogenic nuclease reverse transcriptase-polymerase chain reaction assay.}, journal = {Comparative medicine}, volume = {54}, number = {3}, pages = {288-292}, pmid = {15253275}, issn = {1532-0820}, support = {R01 RR14072/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Biological Assay ; Cloning, Molecular ; DNA Primers ; L Cells ; Lactate dehydrogenase-elevating virus/genetics/*isolation &amp; purification ; Mice ; Reverse Transcriptase Polymerase Chain Reaction/methods ; }, abstract = {Lactate dehydrogenase-elevating virus (LDEV) induces persistent infections in laboratory mice, alters in vivo physiology, and is a common contaminant of biological materials such as transplantable tumor cell lines. The fluorogenic nuclease reverse transcriptase polymerase chain reaction (fnRT-PCR) assay combines RT-PCR analysis with an internal fluorogenic hybridization probe, thereby eliminating post-PCR processing and potentially enhancing specificity. An fnRT-PCR assay specific for LDEV was therefore developed by targeting primer and probe sequences to a unique region of the LDEV nucleocapsid (VP1) gene. Using the LDEV fnRT-PCR assay, we detected only LDEV and did not detect other RNA viruses that are capable of naturally infecting rodents. Using this assay, we detected as little as 10 fg of LDEV RNA; the assay was 10-fold less sensitive when directly compared with the mouse bioassay (measurement of serum LD after inoculation), without the problematic false-positive serum LD enzyme elevations associated with the mouse bioassay. Using the fnRT-PCR assay, we also were able to detect viral RNA in numerous tissues and in feces collected from experimentally inoculated C3H/HeN mice, but we did not detect any viral RNA in similar samples collected from age- and strain-matched mock-infected mice. Finally, using the fnRT-PCR assay, we were able to detect LDEV RNA in biological samples that had previously been determined to be contaminated with LDEV by use of the mouse bioassay and an RT-PCR assay at another laboratory. In conclusion, the LDEV fnRT-PCR assay is a potentially high-throughput diagnostic assay for detection of LDEV in mice and contaminated biological materials.}, }
@article {pmid15227973, year = {2003}, author = {Erko, B and Medhin, G and Balcha, F and Raje, S}, title = {Evaluation of pilot control trial of intestinal schistosomiasis in the Finchaa Sugar Estate, Ethiopia.}, journal = {Ethiopian medical journal}, volume = {41}, number = {2}, pages = {141-150}, pmid = {15227973}, issn = {0014-1755}, mesh = {Adolescent ; Adult ; *Agriculture ; Animals ; Biomphalaria/drug effects/*parasitology ; Child ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Fresh Water/*parasitology ; Health Surveys ; Humans ; Male ; Middle Aged ; Pest Control/*methods ; Phytolacca dodecandra/*poisoning ; Pilot Projects ; Prevalence ; Schistosomiasis mansoni/epidemiology/*prevention &amp; control ; }, abstract = {Intestinal schistosomiasis is undergoing a rapid increase in magnitude in Finchaa Sugar Estate in Ethiopia. A pilot control trial of intestinal schistosomiasis was instituted in 1995 to reduce the magnitude of the disease and introduce sustainable schistosomiasis control approaches in the Sugar Estate. Following initial parasitological survey of all the camps in the Sugar Project area in 1995 using Kato method, mass chemotherapy of the heavily infected residents of Camp 7 and selective treatment of lightly infected residents of other camps were made using praziquantel. Endod (type 44) was applied to transmission sites along Fekerie stream in Camp 7 on quarterly basis whenever Biomphalaria pfeifferi was detected. Other inputs to the project as parts of capacity building included transplantation of Endod cuttings (type 44), training and health education. Cross sectional parasitological surveys were made in 1998 to assess the impact of the pilot control trial. The results of stool examination showed that the prevalence of schistosomiasis was reduced from 30% in 1995 to 26% in 1998 among residents of Camp 7 and the intensity of infection from 198 eggs per gram of feces (EPG) in 1995 to 85 EPG in 1998. Similarly, the prevalence of infection among children in Finchaa Valley Elementary School was reduced from 78% in 1994 to 56% in 1998 and the reduction in respective intensity of infection was from 283 EPG to 114 EPG. Although significant reduction in the magnitude of the disease was not achieved, the control activities were taken over by the Sugar Project Polyclinic to ensure sustainability. In addition to chemotherapy and snail control using Endod, other disease non-specific methods such as health education should be used to get maximum benefit from such facilities as latrines, and ensure participation of the community in order to sustain the control activities.}, }
@article {pmid15182775, year = {2004}, author = {Conraads, VM and Jorens, PG and De Clerck, LS and Van Saene, HK and Ieven, MM and Bosmans, JM and Schuerwegh, A and Bridts, CH and Wuyts, F and Stevens, WJ and Anker, SD and Rauchhaus, M and Vrints, CJ}, title = {Selective intestinal decontamination in advanced chronic heart failure: a pilot trial.}, journal = {European journal of heart failure}, volume = {6}, number = {4}, pages = {483-491}, doi = {10.1016/j.ejheart.2003.12.004}, pmid = {15182775}, issn = {1388-9842}, mesh = {Adult ; Aged ; Bacteriological Techniques ; Biomarkers/blood ; Chronic Disease ; Cytokines/metabolism ; *Decontamination ; Endothelium, Vascular/metabolism/microbiology ; Endotoxins/metabolism ; Feces/chemistry/microbiology ; Female ; Gram-Negative Aerobic Bacteria/metabolism ; Heart Failure/*metabolism ; Humans ; Intestinal Mucosa/*metabolism ; Intestines/blood supply/microbiology ; Lipopolysaccharide Receptors/biosynthesis ; Male ; Middle Aged ; Monocytes/metabolism ; Pilot Projects ; Prospective Studies ; Regional Blood Flow/physiology ; Severity of Illness Index ; Vasodilation/physiology ; }, abstract = {BACKGROUND AND AIMS: Endotoxin, derived from intestinal aerobic Gram-negative bacilli (AGNB), could be an important monocyte activator in chronic heart failure (CHF). The effect of selective decontamination of the digestive tract (SDD) on intracellular monocyte cytokine production, monocyte CD14 expression, circulating endotoxin and cytokines, and flow-mediated dilation (FMD) was studied in patients with severe CHF.<br><br>METHODS AND RESULTS: Ten patients with CHF (NYHA class III-IV) were enrolled in a non-placebo controlled pilot trial involving the administration of SDD (polymyxin B, tobramycin) for 8 weeks. One patient was later excluded due to cardiac transplantation. Before treatment, after 4 and 8 weeks therapy, and 6 weeks post-treatment, monocyte CD14 expression, intracellular monocyte production of interleukin-1beta [IL-1beta], interleukin-6 [IL-6], tumour necrosis factor (TNF)-alpha with and without lipopolysaccharide (LPS) stimulation were measured. Concentrations of endotoxin and cytokines (IL-1beta, IL-6, TNF-alpha) were also determined. AGNB in faeces, intestinal endotoxin and FMD were assessed at baseline, after 4 weeks of treatment and 6 weeks post-treatment. SDD eradicated intestinal AGNB (P<0.00001) and decreased faecal endotoxin concentrations (P<0.00001). There was a significant decline in monocyte CD14 expression (P=0.03) and in IL-1beta (P=0.0001), IL-6 (P=0.02) and TNF-alpha (P=0.0002) production after 4 and 8 weeks of treatment in the basal state and for IL-1beta (P=0.008) and IL-6 (P=0.005) after LPS stimulation. FMD significantly improved at 4 weeks and returned to baseline after treatment discontinuation (P=0.002). Circulating concentrations of endotoxin and cytokines remained unchanged.<br><br>CONCLUSION: Reduction of the intestinal endotoxin pool led to a decrease in monocyte CD14 expression and intracellular cytokine production in patients with severe CHF. The improvement of peripheral endothelial function could be a marker of the anti-inflammatory effect of SDD.}, }
@article {pmid15137961, year = {2004}, author = {Dev, VR and Gupta, A}, title = {Plastic and reconstructive surgery approaches in the management of anal cancer.}, journal = {Surgical oncology clinics of North America}, volume = {13}, number = {2}, pages = {339-353}, doi = {10.1016/j.soc.2003.12.008}, pmid = {15137961}, issn = {1055-3207}, mesh = {Anus Neoplasms/*surgery ; Electric Stimulation Therapy/instrumentation ; Humans ; Muscle, Skeletal/transplantation ; Quality of Life ; *Plastic Surgery Procedures ; Rectum/surgery ; Skin Transplantation/methods ; Surgical Flaps ; Treatment Outcome ; }, abstract = {Various reliable reconstructive options are available for treatment of perineal and perianal skin and soft tissue defects resulting from tumor ablation. Indications for TAR include the following: very low rectal cancers, in which low anterior resection or resection with coloanal anastomosis is not possible: persistent or recurrent anal cancer that has failed to respond to chemoradiation therapy; and previous rectal excision with either recurring colostomy complications or an unacceptable quality of life with a stoma. Of course, adequate surgical oncologic principles must not be compromised to enhance sphincter reconstruction. Either primary reconstruction at the time of cancer excision or secondary reconstruction at a later date is an acceptable alternative. Most investigators believe that primary reconstruction is technically easier and associated with fewer complications. Secondary reconstruction provides the advantage of oncologic certainty. Double dynamic graciloplasty after APR has proved to be anoncologically sound procedure with a good chance of continence and a life without a stoma in most patients. Finally, the preliminary experience with new techniques of electrode implants encourages further application. In most patients who have rectal cancer, a sphincter-saving resection can avoid the need for a permanent stoma. Very low rectal tumors, however, still require an APR as the treatment of choice when a safe coloanal anastomosisis not possible. In recent years, several authors have reported their experience on sphincteric reconstruction after APR. Most of these authors used gracilis muscles transposed from the thigh to the perineum (graciloplasty) to surround a coloperineal anastomosis after pull-through of the distal colon. The best way to achieve fecal continence is to obtain a mechanically sufficient contraction of the sphincter. Electrostimulation of the transposed gracilis muscles creates an essential framework for their postoperative muscular growth and contractility. In particular, adoption of continuous low-frequency stimulation has proved to be effective in increasing fatigue resistance of the transposed muscles, allowing their continuous "pseudotonic" contraction. Despite the general acceptance of the efficacy of this scheme, there are significant variations in various authors' experiences pertaining to graciloplasty configuration, surgical timing of resection and transposition, and electrostimulation device use and implantation.}, }
@article {pmid15108091, year = {2004}, author = {Shatari, T and Fujita, M and Kodaira, S}, title = {Dynamic graciloplasty resulting fecal continence without electrical stimulation: report of a case.}, journal = {Surgery today}, volume = {34}, number = {5}, pages = {463-465}, doi = {10.1007/s00595-003-2700-6}, pmid = {15108091}, issn = {0941-1291}, mesh = {Adult ; Anal Canal/physiopathology/*surgery ; Defecation/physiology ; Electric Stimulation Therapy ; Fecal Incontinence/physiopathology/*surgery ; Humans ; Male ; Muscle Contraction/physiology ; Muscle, Skeletal/physiology/*transplantation ; }, abstract = {A 32 year-old man received dynamic graciloplasty for fecal incontinence due to a pelvic fracture. The perception of stool was obtained soon after the colostomy closure. Defecography and a manometric study showed that the patient could contract the transposed gracilis muscle independently. While the resting anal canal pressure remained low (52 cmH(2)O), he maintained excellent continence without stimulation. When stimulated, the anal canal pressure rose to 112 cmH(2)O. Electrical stimulation is therefore not always necessary for a good function after dynamic graciloplasty.}, }
@article {pmid15105900, year = {2004}, author = {Tímár, J}, title = {[Report of the National Oncology Research and Developement Consortium, 2003].}, journal = {Magyar onkologia}, volume = {48}, number = {1}, pages = {75-79}, pmid = {15105900}, issn = {0025-0244}, mesh = {2-Methoxyestradiol ; Adult ; Animals ; *Antineoplastic Agents/pharmacology ; *Biomarkers, Tumor/analysis ; *Biomedical Research ; Bone Neoplasms/epidemiology/genetics/secondary ; *Breast Neoplasms/diagnosis/epidemiology/genetics/therapy ; Child ; *Colorectal Neoplasms/diagnosis/epidemiology/genetics/therapy ; DNA Methylation ; Disease Models, Animal ; Disease Progression ; Epoetin Alfa ; Erythropoietin/pharmacology ; Estradiol/*analogs &amp; derivatives/pharmacology ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Genetic Markers ; *Head and Neck Neoplasms/diagnosis/epidemiology/genetics/therapy ; Heparin, Low-Molecular-Weight/pharmacology ; Humans ; Hungary/epidemiology ; Incidence ; Male ; *Melanoma/diagnosis/epidemiology/genetics/therapy ; Microsatellite Repeats ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Predictive Value of Tests ; Recombinant Proteins ; Transplantation, Heterologous ; }, abstract = {Consorcial projects focused on 5 cancer types, breast-, colorectal-, head and neck- and pediatric cancers, and malignant melanoma. Breast cancer studies revealed unique splicing mechanisms concerning BRCA1. In sporadic breast cancers the involvement of DNA-repair genes was proved to be dependent on the histological type. Bone-metastatic tumors have been characterized by decreased NM23 and increased c-met and p53 expressions. C-erbB2 genotype of the primary tumor was not maintained frequently in bone metastases. Application of DNA-microarray and quantitative PCR technologies improved the prediction of therapeutic sensitivity of breast cancers. Colorectal cancer studies revealed regional inhomogenities (clusters) in various geographical regions of Hungary, which were distinct in the case of colonic and rectal cancers. To increase the sensitivity of fecal blood test of colorectal cancer screening, a new double-antibody test was developed and tested in a large cohort of patients. Genetic analysis revealed that hypermethylation is a significant factor in microsatellite instability which, and plays a role in silencing of APC and E-cadherin genes as well. The Hungarian pattern of TS polymorphism was also determined and was correlated not only with the efficacy of 5-FU treatment but with the progression of the disease as well. Population-based studies have been carried out in head and neck cancer patients (HNC) and smokers as well to reveal the genetic background of increasing tumor incidence. These studies revealed polymorphism in XRCC1/3 methylation enzyme gene which has preventive role. Other studies found frequent local immunosuppression in HNC patients. Studies indicated that the success of irradiation in this cancer type is dependent on the anti-vascular effects. Pediatric cancer studies determined the parameters of neuroblastoma screening based on VMA measurements. New splice variants of the WT1 gene involved in the monitoring of MRD of ALL patients was also described this year. We also obtained positive experimental data for the retinoic acid therapy of ALL. Melanoma studies extensively used DNA-microarray technology which identified 4 melanoma-specific and 2 melanoma progression-specific genes. In experimental human melanoma xenograft models we have identified 3 anti-metastatic agents: low molecular weight heparin, 2-methoxyestradiol and erythropoietin-alpha, where the later was characterized by specific effects on tumor vasculature.}, }
@article {pmid15097858, year = {2004}, author = {Saruc, M and Standop, S and Standop, J and Nozawa, F and Itami, A and Pandey, KK and Batra, SK and Gonzalez, NJ and Guesry, P and Pour, PM}, title = {Pancreatic enzyme extract improves survival in murine pancreatic cancer.}, journal = {Pancreas}, volume = {28}, number = {4}, pages = {401-412}, doi = {10.1097/00006676-200405000-00009}, pmid = {15097858}, issn = {1536-4828}, mesh = {Amylases/blood ; Animals ; Cell Division ; Cell Line, Tumor ; Enzyme Stability ; Fats/analysis ; Feces/chemistry ; Growth Substances/biosynthesis/genetics ; Humans ; Immunohistochemistry ; Lipase/blood ; Male ; Mice ; Mice, Nude ; Pancreatic Neoplasms/metabolism/pathology/*therapy ; Pancreatin/*therapeutic use ; RNA, Messenger/metabolism ; Survival Analysis ; Swine ; Urinalysis ; Xenograft Model Antitumor Assays ; }, abstract = {OBJECTIVES: The disappointing current therapeutic approaches for pancreatic cancer (PC) represent an urgent need for the development of novel methods to control the disease. Based on a recent report on the effectiveness of pancreatic enzyme therapy, we examined the effect of porcine pancreatic enzyme extracts (PPE) on human PC xenografts in nude mice.<br><br>METHODS: The malignant human PC cell line AsPC1 was transplanted into the pancreas of male beige XID nude mice that were treated or not with PPE in drinking water. The survival, size, and volume of tumors, plasma pancreatic enzyme levels, fecal fat, and urine were examined as were the expression of transforming growth factor alpha, insulinlike growth factor-I, epidermal growth factor, epidermal growth factor receptor, apoptosis, and proliferation rate of tumor cells.<br><br>RESULTS: PPE-treated mice survived significantly longer than the control group (P < 0.002). Tumors in the PPE-treated group were significantly smaller than in the control group. All mice in the control group showed steatorrhea, hyperglucosuria, hyperbilirubinuria, and ketonuria at early stages of tumor growth, whereas only a few in the treated group showed some of these abnormalities at the final stage. There were no differences in the expression of growth factors, epidermal growth factor receptor, or the apoptotic rate between the tumors of treated and control mice.<br><br>CONCLUSIONS: The treatment with PPE significantly prolongs the survival of mice with human PC xenografts and slows the tumor growth. The data indicate that the beneficial effect of PPE on survival is primarily related to the nutritional advantage of the treated mice.}, }
@article {pmid15094274, year = {2004}, author = {Müller, HM and Oberwalder, M and Fiegl, H and Morandell, M and Goebel, G and Zitt, M and Mühlthaler, M and Ofner, D and Margreiter, R and Widschwendter, M}, title = {Methylation changes in faecal DNA: a marker for colorectal cancer screening?.}, journal = {Lancet (London, England)}, volume = {363}, number = {9417}, pages = {1283-1285}, doi = {10.1016/S0140-6736(04)16002-9}, pmid = {15094274}, issn = {1474-547X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Colorectal Neoplasms/*diagnosis/genetics ; *DNA Methylation ; Feces/*chemistry ; Female ; Genetic Markers ; Humans ; Male ; *Membrane Proteins ; Middle Aged ; Proteins/*genetics ; Sensitivity and Specificity ; }, abstract = {DNA methylation is a common molecular alteration in colorectal cancer cells. We report an assessment of faecal DNA from patients with colorectal cancer and controls to determine the feasibility, sensitivity, and specificity of this approach. By use of MethyLight analysis of faecal DNA from three independent sets of patients, we identified SFRP2 methylation as a sensitive single DNA-based marker for identification of colorectal cancer in stool samples (sensitivity 90% [CI 56-100] and specificity 77% [46-95] in the training set [n=23]; sensitivity 77% [46-95] and specificity 77% [46-95] in an independent test set [n=26]). Whether a combination of genetic and epigenetic markers will identify colorectal cancer at an early stage remains to be shown.}, }
@article {pmid15085439, year = {2004}, author = {Altomare, DF and Rinaldi, M and Petrolino, M and Ripetti, V and Masin, A and Ratto, C and Trerotoli, P and Monitillo, V and Lobascio, P and De Fazio, M and Guglielmi, A and Memeo, V}, title = {Reliability of electrophysiologic anal tests in predicting the outcome of sacral nerve modulation for fecal incontinence.}, journal = {Diseases of the colon and rectum}, volume = {47}, number = {6}, pages = {853-857}, doi = {10.1007/s10350-004-0524-0}, pmid = {15085439}, issn = {0012-3706}, mesh = {Aged ; Anal Canal/*physiopathology/surgery ; Electrodes, Implanted ; Electromyography/*methods ; Fecal Incontinence/*physiopathology/*surgery ; Female ; Humans ; Lumbosacral Plexus/*physiopathology/surgery ; Male ; Middle Aged ; Predictive Value of Tests ; Prosthesis Implantation/methods ; Reproducibility of Results ; Retrospective Studies ; Treatment Outcome ; }, abstract = {INTRODUCTION: Sacral nerve modulation has been demonstrated to be a new efficacious treatment for fecal incontinence. The effectiveness of the procedure is preliminarily tested by means of a peripheral nerve evaluation. Integrity of the sacral neural pathway is generally believed to be a necessary condition for a good response, but no data are available to confirm whether electrophysiologic anal tests are predictive of the clinical outcome of the peripheral nerve evaluation.<br><br>METHODS: Eighty-two incontinent patients underwent the peripheral nerve evaluation after full evaluation of the anorectal physiology. Univariate analysis was performed, and the positive predictive value, sensitivity, and specificity were calculated for each of the tests.<br><br>RESULTS: Forty-six patients had successful results to the peripheral nerve evaluation and were subjected to permanent implant of a sacral electrostimulator. Anal sphincter electromyography had been performed in 60 patients, whereas pudendal nerve terminal motor latency had been assessed in 68 and evoked sacral potentials in 29 patients. Anal electromyography was statistically related to the outcome of the peripheral nerve evaluation (P = 0.0004) with a positive predictive value of 81 percent, a sensitivity of 44 percent, and a specificity of 81 percent. Pudendal nerve terminal motor latency on the right side did not correlate with the outcome, but left pudendal nerve terminal motor latency was weakly correlated (P = 0.02), although both tests had a low positive predicting value and sensitivity vs. good specificity. Evoked sacral potentials did not correlate with the outcome and had a low positive predictive value, sensitivity, and specificity.<br><br>CONCLUSIONS: Simple anal sphincter electromyography can predict the outcome of the peripheral nerve evaluation with good positive predictive value and specificity in patients with fecal incontinence. Other, more expensive, electrophysiologic anal tests do not add further prognostic information.}, }
@article {pmid15050144, year = {2004}, author = {Berney, T and Genton, L and Buhler, LH and Raguso, CA and Charbonnet, P and Pichard, C and Morel, P}, title = {Five-year follow-up after pediatric living related small bowel transplantation between two monozygotic twins.}, journal = {Transplantation proceedings}, volume = {36}, number = {2}, pages = {316-318}, doi = {10.1016/j.transproceed.2004.01.103}, pmid = {15050144}, issn = {0041-1345}, mesh = {Adolescent ; Body Composition ; Failure to Thrive/surgery ; Growth ; Humans ; Infant, Newborn ; Intestinal Absorption ; Intestine, Small/*transplantation ; Living Donors ; Male ; Skin Transplantation ; Time Factors ; Treatment Outcome ; Twins, Monozygotic ; }, abstract = {Two 13-year-old monozygotic twins were used for living related small bowel transplantation (SBTx). The recipient presented with short gut syndrome secondary to complicated abdominal surgery. The indication for SBTx was based on a failure to thrive and a poor tolerance of TPN. The donor was an identical twin, as demonstrated by skin graft acceptance, which allowed performance of SBTx without immunosuppression. Growth charts were used to follow intestinal absorption functions and body composition. The donor was used as a control for the recipient. The recipient, who was transplanted with 160 cm of donor ileum, was discharged on postoperative day 62 on a regular diet. Before SBTx the recipient was 10 kg lighter in body weight than the donor, a gap that was progressively reduced over the follow-up period. A height deficit of 3 cm reversed within 1 year after SBTx. A 10-kg deficit in fat-free body mass was completely extinguished within 18 months. By 18 months posttransplant, recipient serum albumin and prealbumin were normal and comparable to donor values. d-Xylose absorption in the recipient remained lower than that in the donor. Within 6 months fecal fat excretion normalized in the recipient. d-Xylose absorption and fecal fat excretion were always within a normal range in the donor.}, }
@article {pmid15042689, year = {2004}, author = {Safdar, A and Malathum, K and Rodriguez, SJ and Husni, R and Rolston, KV}, title = {Strongyloidiasis in patients at a comprehensive cancer center in the United States.}, journal = {Cancer}, volume = {100}, number = {7}, pages = {1531-1536}, doi = {10.1002/cncr.20120}, pmid = {15042689}, issn = {0008-543X}, mesh = {Adolescent ; Adult ; Aged ; Antinematodal Agents/therapeutic use ; Bronchoalveolar Lavage ; Child ; Feces/parasitology ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*complications/parasitology ; Retrospective Studies ; Strongyloidiasis/complications/drug therapy/*epidemiology ; Thiabendazole/therapeutic use ; Treatment Outcome ; United States ; }, abstract = {BACKGROUND: The frequency of Strongyloides stercoralis infestation and complication in patients with cancer in the United States is unknown.<br><br>METHODS: The authors performed a retrospective analysis of S. stercoralis infection in patients who were undergoing cancer treatment at The University of Texas M. D. Anderson Cancer Center (Houston, TX).<br><br>RESULTS: The overall S. stercoralis infection frequency was approximately 1.0 per 10,000 new cancer cases between 1971 and 2003. Twenty-two of 25 patients (88%) were U.S. residents (19 from Texas; 1 each from Mississippi, Tennessee, and Puerto Rico), and the remaining 3 (13%) were from Latin America. Thirteen (52%) had solid-organ malignancies, whereas 12 (48%) had hematologic malignancies (lymphoma or multiple myeloma, n=8; leukemia, n=3; aplastic anemia, n=1). Twelve patients (48%) received systemic corticosteroids, 9 (36%) received antineoplastic therapy, and 2 underwent hematopoietic stem cell transplantation (HSCT). Diarrhea was reported in 13 patients (57%), and eosinophilia was observed in 11 patients (48%); 4 patients (16%) had probable hyperinfection syndrome (in 3 cases of polymicrobial gram-negative bacteremia, 1 patient had Klebsiella pneumoniae pneumonia, whereas 1 patient presented with K. pneumoniae lung infection alone). Evidence of definite pulmonary hyperinfection syndrome was observed in 2 HSCT recipients (8%). Fourteen (74%) of 19 patients responded to thiabendazole therapy. Two patients with definite pulmonary hyperinfection syndrome developed fatal S. stercoralis hemorrhagic alveolitis despite receiving high-dose thiabendazole plus ivermectin therapy.<br><br>CONCLUSIONS: In the current study, strongyloidiasis was uncommon in patients with cancer and remained localized in individuals with solid-organ malignancies. Definite pulmonary accelerated autoinfections were observed only in HSCT recipients. Therefore, pre-HSCT S. stercoralis screening in individuals from endemic regions of the United States warrants further study.}, }
@article {pmid14994111, year = {2004}, author = {Kostov, DV and Temelkov, TD and Dragnev, NA and Kobakov, GL and Ivanov, KD}, title = {Smooth muscle sphincteroplasty in colostomy.}, journal = {Diseases of the colon and rectum}, volume = {47}, number = {4}, pages = {486-493}, doi = {10.1007/s10350-003-0082-x}, pmid = {14994111}, issn = {0012-3706}, mesh = {Adult ; Anal Canal/pathology/*surgery ; Colostomy/*adverse effects ; Fecal Incontinence/etiology/*surgery ; Female ; Humans ; Male ; Middle Aged ; Muscle, Smooth/*surgery ; Therapeutic Irrigation ; Treatment Outcome ; }, abstract = {PURPOSE: The present work elaborated on Schmidt's idea of an effective smooth muscle sphincteroplasty. The aim of the study was to analyze the effects on the patients with a lower quadrant colostomy constructed after abdominoperineal extirpation of a modified smooth muscle sphincteroplasty combined with colon irrigations.<br><br>METHODS: Seventy-two rectal cancer patients (39 men and 33 women, median age, 54.5 years) with smooth muscle sphincteroplasty and 20 controls with conventional colostomy using colon irrigations (11 men and 9 women, median age, 63.2 years) were examined. A modified smooth muscle wrap of the colostomy with a free graft of a 4-cm-long colon segment without mucosa was applied. In this precolostomy segment a high intraluminal pressure was achieved. The functional capacity and anatomic integrity of the transplanted smooth muscle graft were examined manometrically, electromyographically, and histomorphologically. The functional activity of the colostomy was assessed by periodic recording of the number of "spontaneous" and "directed" defecations.RESULTS. In the patients with smooth muscle sphincteroplasty, the basal intraluminal pressure of the precolostomy segment two years after operation measured 29.7 mmHg. After dilatation of the transplant, these pressures reached up to 43 mmHg (P < 0.001). The weekly "spontaneous" stools were 3 to 5 times less frequent than in the controls (P < 0.001).<br><br>CONCLUSIONS: The modified smooth muscle sphincteroplasty offers operative-technical opportunities for increasing intraluminal pressure in the precolostomy colon segment. Its combination with colonic irrigations facilitates control of the evacuatory rhythm and "spontaneous" stools in colostomy patients, thus improving their quality of life.}, }
@article {pmid14991498, year = {2004}, author = {Saunders, JR and Williams, NS and Eccersley, AJ}, title = {The combination of electrically stimulated gracilis neoanal sphincter and continent colonic conduit: a step forward for total anorectal reconstruction?.}, journal = {Diseases of the colon and rectum}, volume = {47}, number = {3}, pages = {354-63; discussion 363-6}, doi = {10.1007/s10350-003-0061-2}, pmid = {14991498}, issn = {0012-3706}, mesh = {Abdomen/surgery ; Adolescent ; Adult ; Aged ; Anal Canal/*physiopathology ; Anus, Imperforate/complications/*surgery ; Combined Modality Therapy ; *Electric Stimulation Therapy/adverse effects ; Enema/adverse effects/*methods ; Fecal Incontinence/etiology/*therapy ; Female ; Humans ; Infections/etiology ; Male ; Middle Aged ; Muscle Contraction/physiology ; Muscle, Skeletal/*physiopathology/transplantation ; Perineum/surgery ; Retrospective Studies ; Treatment Outcome ; }, abstract = {PURPOSE: Patients undergoing total anorectal reconstruction for anorectal atresia or following abdominoperineal resection of the rectum do not fare as well after an electrically stimulated gracilis neoanal sphincter as patients with incontinence alone. This retrospective study reports the outcome for the combination of a continent colonic conduit or antegrade continence enema procedure with an electrically stimulated gracilis neoanal sphincter in patients with atresia or following an abdominoperineal resection of the rectum as part of total anorectal reconstruction to overcome combined incontinence and evacuatory dysfunction.<br><br>METHODS: Between September 1994 and September 1999, 11 continent colonic conduits were fashioned in 11 patients with an electrically stimulated gracilis neoanal sphincter as part of total anorectal reconstruction for end-stage fecal incontinence. In addition, three patients had an antegrade continence enema procedure in situ, one of which was converted to a colonic conduit at a later stage. Five patients had a colonic conduit fashioned subsequent to an electrically stimulated gracilis neoanal sphincter, four had both procedures in a combined operation, and five had a conduit formed before an electrically stimulated gracilis neoanal sphincter (including the three with an antegrade continence enema procedure).<br><br>RESULTS: Median follow-up was 53 (range, 7-98) months until July 2002 or until exit from this study group because of end stoma formation (n = 6). Seven patients (50 percent) had a successful outcome, defined as continent to solid and liquid stool. Overall, eight patients (57 percent) reported some degree of improvement in their bowel function and were successfully managed by this combination of procedures. An end stoma was formed in six patients (43 percent).<br><br>CONCLUSIONS: The combination of antegrade irrigation via a colonic conduit or an antegrade continence enema procedure provides a successful outcome for some patients when incorporated into total anorectal reconstruction, provided that sepsis does not occur, thus avoiding permanent stoma formation. The combination of these procedures may represent an improvement in total anorectal reconstruction and warrants further clinical trial.}, }
@article {pmid14991162, year = {2004}, author = {Diepolder, HM}, title = {[Prevention and therapy of viral hepatitis].}, journal = {Der Internist}, volume = {45}, number = {2}, pages = {197-209}, pmid = {14991162}, issn = {0020-9554}, mesh = {Antiviral Agents/administration &amp; dosage/adverse effects ; Drug Therapy, Combination ; Germany ; Hepatitis A/diagnosis/drug therapy/prevention &amp; control/transmission ; Hepatitis A Vaccines/administration &amp; dosage ; Hepatitis B/diagnosis/drug therapy/prevention &amp; control/transmission ; Hepatitis B Vaccines/administration &amp; dosage ; Hepatitis B, Chronic/diagnosis/drug therapy/prevention &amp; control ; Hepatitis C, Chronic/drug therapy/prevention &amp; control ; Hepatitis D/drug therapy/prevention &amp; control ; Hepatitis, Viral, Human/diagnosis/drug therapy/*prevention &amp; control/transmission ; Humans ; Interferons/administration &amp; dosage/adverse effects ; Prognosis ; Reverse Transcriptase Inhibitors/administration &amp; dosage/adverse effects ; Risk Factors ; Treatment Outcome ; }, abstract = {The hepatitis viruses A to E are biologically and clinically heterogeneous: hepatitis A and E are transmitted faecal-orally and never lead to chronic infection. In contrast, the other viruses-B, C, D-are transmitted parenterally and are the leading causes of chronic viral infections in humans worldwide. Highly efficient vaccines are available against hepatitis A and B. The therapeutic armamentarium for chronic hepatitis B and C has significantly expanded during the last several years. Two nucleoside analogues, lamivudine and adefovir, have been licensed for the treatment of chronic hepatitis B and can be used for patients in whom interferon would be contra-indicated such as decompensated cirrhotics. Standard therapy for chronic hepatitis C is a combination of a pegylated interferon-alpha and ribavirin, which can lead to sustained viral clearance in more than 50% of treatable patients. Patients with decompensated cirrhosis can be treated by liver transplantation which offers a 5-year-survival of greater than 80%.}, }
@article {pmid14870558, year = {2000}, author = {Georgescu, A and Ivan, O and Oancea, A}, title = {[Anal sphincter restoration with gracilis muscular flap].}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {95}, number = {5}, pages = {469-475}, pmid = {14870558}, issn = {1221-9118}, mesh = {Adolescent ; Adult ; Anal Canal/*surgery ; Child ; Electric Stimulation Therapy ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Plastic Surgery Procedures ; *Surgical Flaps ; }, abstract = {One of the efficient possibilities for regaining the anal continence consists of using the pediculated gracilis muscular flap. The electrostimulation of the anal neosphincter and the functional rehabilitation are of major importance in obtaining a good result. The present paper is based on 5 cases in which this method was applied.}, }
@article {pmid14740123, year = {2004}, author = {Baeten, CG}, title = {[Anal sphincter replacement].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {75}, number = {1}, pages = {21-25}, pmid = {14740123}, issn = {0009-4722}, mesh = {Anal Canal/*surgery ; Defecation ; Electric Stimulation Therapy ; Electrodes, Implanted ; Fecal Incontinence/prevention &amp; control ; Humans ; Muscle, Skeletal/*transplantation ; Patient Selection ; Rectal Neoplasms/*surgery ; }, abstract = {Presently, deep rectal carcinoma is usually treated by deep anterior rectal resection and colonal anastomosis. Abdominoperineal resection is needed only for the very few patients whose tumors infiltrate the pelvic base or sphincter musculature. This means the loss of normal anal function and thus of normal defecation. Many patients find the idea of a stoma unacceptable. In our experience, the construction of a functional neoanus after abdominoperineal rectal resection is a suitable option for patients in good general health and who are highly motivated.}, }
@article {pmid14655202, year = {2003}, author = {Marx, M and Marx, C and Luft, FC}, title = {Dysarthria in a patient with probable acquired chloridorrhea.}, journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation}, volume = {42}, number = {6}, pages = {1283-1286}, doi = {10.1053/j.ajkd.2003.08.031}, pmid = {14655202}, issn = {1523-6838}, mesh = {Adult ; Alkalosis/etiology ; *Antiporters ; Bicarbonates/metabolism ; Carrier Proteins/physiology ; Chloride-Bicarbonate Antiporters ; Chlorides/*metabolism ; Consciousness Disorders/*etiology ; Crohn Disease/surgery ; Diarrhea/*complications ; Dysarthria/*etiology ; Feces/chemistry ; Female ; Graft Rejection/*complications ; Humans ; Ileostomy ; Intestinal Pseudo-Obstruction/etiology ; Intestine, Small/*transplantation ; Membrane Proteins/physiology ; Parenteral Nutrition ; Postoperative Complications/*etiology ; Reoperation ; Short Bowel Syndrome/surgery ; Sulfate Transporters ; }, abstract = {The authors encountered a patient who had profound hypochloremic metabolic alkalosis after developing profuse diarrhea related to rejection of her small bowel transplant. Her ileostomy fluid showed massive electrolyte losses and was exceptionally high in chloride content. She improved with volume substitution and a proton pump inhibitor, although she subsequently required repeat small bowel transplant. The authors speculate that an impaired "downregulated in adenoma" gene (DRA) that enclodes an apical Cl(-)/HO(-)(HCO(3)) exchanger may have contributed to an acquired chloridorrhea in this patient.}, }
@article {pmid14655200, year = {2003}, author = {Asif, A and Byers, P and Vieira, CF and Merrill, D and Gadalean, F and Bourgoignie, JJ and Leclercq, B and Roth, D and Gadallah, MF}, title = {Peritoneoscopic placement of peritoneal dialysis catheter and bowel perforation: experience of an interventional nephrology program.}, journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation}, volume = {42}, number = {6}, pages = {1270-1274}, doi = {10.1053/j.ajkd.2003.08.029}, pmid = {14655200}, issn = {1523-6838}, mesh = {Abdomen, Acute/etiology ; Adult ; Aged ; Anti-Bacterial Agents ; Catheterization/*adverse effects ; Combined Modality Therapy ; Diabetic Nephropathies/complications ; Drug Therapy, Combination/therapeutic use ; Feces ; Female ; Gases ; Humans ; Immunosuppressive Agents/adverse effects ; Intestinal Perforation/diagnosis/*etiology/surgery/therapy ; Kidney Failure, Chronic/chemically induced/therapy ; Laparoscopy/*adverse effects ; Lung Transplantation ; Male ; Middle Aged ; Peritoneal Dialysis/*instrumentation ; Peritonitis/drug therapy/etiology/surgery ; Postoperative Complications/etiology ; Retrospective Studies ; Surgical Instruments ; Tacrolimus/adverse effects ; }, abstract = {BACKGROUND: Bowel perforation is an uncommon but serious complication of peritoneoscopic peritoneal dialysis (PD) catheter insertion. The approach to diagnosis of bowel perforation utilizing this technique has not been previously published. The authors report their experience with the diagnosis and management of bowel perforation in the context of peritoneoscopic placement of PD catheters.<br><br>METHODS: The authors retrospectively reviewed the records of 750 PD catheters inserted over a 12-year period (January 1991 to May 2003) utilizing peritoneoscopic technique.<br><br>RESULTS: Six (0.8%) patients experienced bowel perforation during the procedure. The diagnosis was made immediately during the procedure in 5 (83%) of the 6 patients. Of these 5, peritoneoscopy confirmed intrabowel position of the cannula by visualizing bowel mucosa (n = 3) and hard stool (n = 1). The fifth patient showed extrusion of fecal matter upon trocar withdrawal before peritoneoscopy. All 5 had emanation of foul-smelling gas through the cannula. Bowel rest and broad-spectrum intravenous antibiotics were initiated. Of the 5, 1 required surgery, whereas the others were discharged home after 3 days. The sixth patient had fever, severe peritoneal irritation, and polymicrobial peritonitis the morning after the procedure. In this patient, no evidence of bowel injury was noted during the procedure except for brief emanation of foul-smelling gas. He required surgical intervention.<br><br>CONCLUSION: Bowel perforation can be diagnosed immediately in most patients undergoing peritoneoscopic PD catheter insertion. A majority of these patients can be treated medically. The surgical team should be consulted if the patient shows clinical deterioration or has signs of peritoneal irritation.}, }
@article {pmid14621046, year = {2003}, author = {Rao, K and Sekar, U and Iraivan, KT and Abraham, G and Soundararajan, P}, title = {Blastocystis hominis--an emerging cause of diarrhoea in renal transplant recipients.}, journal = {The Journal of the Association of Physicians of India}, volume = {51}, number = {}, pages = {719-721}, pmid = {14621046}, issn = {0004-5772}, mesh = {Adult ; Animals ; Anti-Infective Agents/therapeutic use ; Blastocystis Infections/drug therapy/*parasitology/pathology ; Blastocystis hominis/*isolation &amp; purification ; Diarrhea/*parasitology ; Feces/parasitology ; Humans ; *Kidney Transplantation ; Male ; Metronidazole/therapeutic use ; Middle Aged ; *Postoperative Complications ; }, abstract = {Blastocystis hominis is an intestinal protozoan that is emerging as an important cause of diarrhea in the immunosuppressed population. We report two cases of diarrhea caused by this organism in renal transplant recipients. The infection was diagnosed promptly by careful stool examination and treated successfully with metronidazole. These case report highlights the fact that unusual parasites like Blastocystis hominis should be looked for and treated in cases of diarrhea occurring in renal transplant recipients. This reduces the rate of post-transplant morbidity and mortality.}, }
@article {pmid14614705, year = {2003}, author = {Pakarinen, MP and Pirinen, P and Lauronen, J and Raivio, P and Kuusanmäki, P and Halttunen, J}, title = {Effects of transection and extrinsic denervation and a model of autotransplantation of the porcine jejunoileum on cholesterol biodynamics.}, journal = {Journal of pediatric surgery}, volume = {38}, number = {11}, pages = {1585-1590}, doi = {10.1016/s0022-3468(03)00569-4}, pmid = {14614705}, issn = {1531-5037}, mesh = {Anastomosis, Surgical ; Animals ; *Autonomic Denervation ; Bile Acids and Salts/metabolism ; Cholesterol/analogs &amp; derivatives/*biosynthesis/blood ; Cholesterol, Dietary/*pharmacokinetics ; Feces/chemistry ; Female ; Ileum/blood supply/innervation/metabolism/*transplantation ; Intestinal Absorption ; Ischemia/metabolism ; Jejunum/blood supply/innervation/metabolism/*transplantation ; Malabsorption Syndromes/*etiology/metabolism ; Models, Animal ; Phytosterols/pharmacokinetics ; Reperfusion Injury/metabolism ; Swine ; Transplantation, Autologous/adverse effects ; Weight Gain ; }, abstract = {BACKGROUND/PURPOSE: Small bowel transplantation impairs enteric function, necessitating transection, extrinsic denervation, and ischemia-reperfusion of the small intestine. The authors investigated how each of these nonimmunologic insides of the transplantation procedure modulates biodynamics of cholesterol and absorption of lipids.<br><br>METHODS: Twenty-three pigs with similar food, cholesterol, and fat intake underwent sham laparotomy (group 1), transection (group 2), extrinsic jejunoileal denervation (group 3), or a model of autotransplantation, including extrinsic jejunoileal denervation with in situ ischemia-reperfusion (group 4). Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis, and absorption, were measured after 2 and 8 weeks.<br><br>RESULTS: When compared with sham laparotomy and transection groups, denervation and autotransplantation significantly decreased weight gain and increased plasma cholesterol precursors and fecal excretion of bile acids. In relation to sham operated animals, transection alone modestly increased plasma plant sterols at 2 weeks and biliary secretion and mass absorption of cholesterol. The latter changes were not observed after denervation or autotransplantation, ie, fractional and total absorption of cholesterol were significantly decreased in autotransplanted pigs when compared with transected controls. As compared with all the other groups, autotransplantation significantly increased bacterial metabolites of neutral sterols in feces and net fecal elimination of cholesterol, mainly as bile acids.<br><br>CONCLUSIONS: Extrinsic autonomic denervation of the jejunoileum, with or without synchronous ischemia-reperfusion, results in increased cholesterol synthesis, bile acid malabsorption, and decreased weight gain. Cholesterol malabsorption may develop gradually after intestinal autotransplantation, and even a short period of ischemia further impairs absorptive function of the denervated jejunoileum, resulting in increased fecal elimination of cholesterol mainly as bile acids.}, }
@article {pmid14605928, year = {2003}, author = {Goldsmith, HS}, title = {Fecal control following pyloric valve transposition after abdominoperineal resection.}, journal = {Techniques in coloproctology}, volume = {7}, number = {2}, pages = {95-101; comment 100-1}, doi = {10.1007/s10151-003-0017-5}, pmid = {14605928}, issn = {1123-6337}, mesh = {Anal Canal/*surgery ; Anastomosis, Surgical ; Animals ; Cats ; Defecation/physiology ; Digestive System Surgical Procedures/methods ; Disease Models, Animal ; Fecal Incontinence/*surgery ; Perineum/*surgery ; Pylorus/*transplantation ; Recovery of Function ; Risk Assessment ; Treatment Outcome ; }, abstract = {BACKGROUND: The objective of this study was to learn if a transposed pyloric valve could be mobilized to the perianal area following an abdominoperineal resection and function as a replacement for the excised anal sphincter.<br><br>METHODS: The study was performed in a surgical research laboratory. Eleven cats were used in the study: 9 served as experimental animals and 2 were controls. The operation involved mobilization of the pyloric valve based on an intact omental pedicle; the proximal side of the pyloric valve was anastomosed to the divided end of the left colon and the distal end of the pyloric valve was sutured to the perianal area.<br><br>RESULTS: The excellent healing of the pyloric valve in its ectopic position was confirmed anatomically and histologically following the sacrifice of the animals. The pyloric valve was effective in maintaining complete fecal control in 4 cats and almost complete fecal continence in 2 other cats. Three other cats developed fecal incontinence due to a perianal fistula, and 2 control cats had complete fecal incontinence.<br><br>CONCLUSION: There appears to be no anatomical or technical reason why the pyloric valve cannot be applied in the human as a replacement for an excised anal sphincter.}, }
@article {pmid14605834, year = {2004}, author = {Racalbuto, A and Aliotta, I and Corsaro, G and Lanteri, R and Di Cataldo, A and Licata, A}, title = {Hemorrhoidal stapler prolapsectomy vs. Milligan-Morgan hemorrhoidectomy: a long-term randomized trial.}, journal = {International journal of colorectal disease}, volume = {19}, number = {3}, pages = {239-244}, pmid = {14605834}, issn = {0179-1958}, mesh = {Activities of Daily Living ; Adult ; Aged ; Anal Canal/physiopathology/surgery ; Fecal Incontinence/etiology ; Female ; Fissure in Ano/etiology/surgery ; Follow-Up Studies ; Hemorrhoids/*surgery ; Humans ; Male ; Manometry ; Middle Aged ; Pain Measurement ; Patient Satisfaction ; Postoperative Complications ; Recovery of Function/physiology ; Rectal Prolapse/*surgery ; *Surgical Staplers ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: The notable success of stapled prolapsectomy in recent years led us to compare this technique with Milligan-Morgan hemorrhoidectomy in terms of the results obtained both in the immediate postoperative period and in the long term.<br><br>PATIENTS AND METHODS: We performed conventional hemorrhoidectomy on 50 randomly selected patients and operated on a further 50 using the stapler technique. The patients were monitored over the immediate postoperative period (e.g., type of anesthesia, mean duration of operation, mean hospitalization time, analgesic administration, time before returning to work) and over a long-term follow-up period of 48 months (later complications such as prolapse relapse, bleeding, stenosis, incontinence).<br><br>RESULTS: The stapled group experienced significantly less pain (mean number of analgesic tablets 2.60 vs. 15.9) and returned to normal activity sooner (8.04 vs. 16.9 days), as reported by other authors. In the long-term follow-up at 48 months, stapled hemorrhoidectomy was found to control prolapse, discharge, and bleeding, with no stenosis or significant incontinence, in 94% of cases.<br><br>CONCLUSION: Our conclusions confirm the excellent advantages of stapled hemorrhoidectomy which allows the rapid recovery of patients and also promises the complete resolution of hemorrhoidal prolapse in the long term.}, }
@article {pmid14586631, year = {2004}, author = {Violi, V and Boselli, AS and De Bernardinis, M and Costi, R and Nervi, G and Bertelè, A and Franzè, A and Roncoroni, L}, title = {Surgical results and functional outcome after total anorectal reconstruction by double graciloplasty supported by external-source electrostimulation and/or implantable pulse generators: an 8-year experience.}, journal = {International journal of colorectal disease}, volume = {19}, number = {3}, pages = {219-227}, pmid = {14586631}, issn = {0179-1958}, mesh = {Aged ; Anal Canal/physiopathology ; *Electric Stimulation Therapy ; Electrodes, Implanted ; Fecal Incontinence/*therapy ; Female ; Humans ; Male ; Manometry ; Middle Aged ; Muscle, Skeletal/physiopathology/*transplantation ; Patient Satisfaction ; Postoperative Complications ; Prospective Studies ; Rectal Neoplasms/surgery ; *Surgical Flaps ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Surgical and functional results after abdominoperineal resection and total anorectal reconstruction by electrostimulated gracilis muscle transposition are still poorly documented. This study prospectively evaluated surgical and functional outcome over time in our patients.<br><br>PATIENTS AND METHODS: Twenty-three patients underwent abdominoperineal resection, coloperineal pullthrough, double graciloplasty, and loop abdominal stoma. Temporary external-source intermittent electrostimulation, biofeedback training, and selective delayed stimulator implantation to improve unsatisfactory results were carried out in the first 13 patients (1st series); thereafter (2nd series) the stimulator was implanted during graciloplasty. Surgical and oncological results were followed up in all patients. Functional results were evaluated in 16 patients who underwent abdominal stoma takedown, eight in each of the two series, by anomanometry (up to 1 year) and our own 0-20 scoring system (up to 8 years from initial surgery).<br><br>RESULTS: The rate of major and minor postoperative complications was 21.7% and 65%, respectively. Continuous electrostimulation proved effective on resting anal pressure. Early clinical assessments showed satisfactory functional results (considered as having a score < or =8) in all first-group patients, including five who had stimulator support, and in one-half of second-group patients. After impairment (at least 2 points) at 1 year in five patients, four of whom were from the first group, all functional results improved and became satisfactory from 5 years on (1st series) and from 4 years on (2nd series).<br><br>CONCLUSION: Despite marked morbidity the high rate of good results, which improved over time, suggests that total anorectal reconstruction is worth being performed as part of abdominoperineal resection in well-selected patients with a strong motivation to avoid a permanent colostomy.}, }
@article {pmid14515299, year = {2003}, author = {Hetzer, FH and Schwizer, W and Kuenzi, W and Demartines, N}, title = {Experimental model of continent colostomy using rectus abdominis neosphincteroplasty.}, journal = {The British journal of surgery}, volume = {90}, number = {10}, pages = {1273-1279}, doi = {10.1002/bjs.4270}, pmid = {14515299}, issn = {0007-1323}, mesh = {Animals ; Biopsy/methods ; Colostomy/*methods ; Electric Stimulation ; Fecal Incontinence/pathology/physiopathology/*surgery ; Female ; Manometry ; Pressure ; Rectus Abdominis/*transplantation ; *Surgical Flaps ; Swine ; }, abstract = {BACKGROUND: Use of dynamic myoplasty to create a continent stoma has produced promising results, but long-term stoma continence has not been achieved. The aim of the study was to establish and test a new model.<br><br>METHODS: Three types of dynamic rectus abdominis sphincteroplasty around a colostomy and two conditioning protocols were tested in ten domestic pigs. Continence was assessed by means of conventional defaecography and neosphincter manometry after 8 and 12 weeks. The neosphincter muscle was studied histologically to assess the transformation of muscle type.<br><br>RESULTS: Use of a distal rectus muscle sling surrounding the stoma by 270 degrees with a low-frequency conditioning protocol achieved a continent colostomy for more than 12 h on each of 5 consecutive days. The neosphincter had a 40-mm high-pressure segment with mean pressure of 74 (range 67-82) mmHg. The proportion of type I muscle fibres increased from 38 (range 32-42) to 74 (range 66-78) per cent after 12 weeks of conditioning.<br><br>CONCLUSION: This pilot study demonstrated the feasibility of a continent stoma in an animal model with a dynamic rectus neosphincter. Long-term results should be confirmed in a larger series before use in humans can be considered.}, }
@article {pmid13680281, year = {2004}, author = {Altomare, DF and Rinaldi, M and Petrolino, M and Monitillo, V and Sallustio, P and Veglia, A and De Fazio, M and Guglielmi, A and Memeo, V}, title = {Permanent sacral nerve modulation for fecal incontinence and associated urinary disturbances.}, journal = {International journal of colorectal disease}, volume = {19}, number = {3}, pages = {203-209}, pmid = {13680281}, issn = {0179-1958}, mesh = {Adult ; Aged ; Anal Canal/physiopathology ; *Electric Stimulation Therapy ; Electrodes, Implanted ; Fecal Incontinence/physiopathology/*therapy ; Female ; Humans ; Lumbosacral Plexus/*physiopathology ; Male ; Manometry ; Middle Aged ; Quality of Life ; Reflex/physiology ; Treatment Outcome ; Urinary Incontinence/physiopathology/*therapy ; Urinary Retention/physiopathology/*therapy ; }, abstract = {BACKGROUND AND AIMS: Sacral nerve modulation (SNM) using an implantable pulse generator is gaining increasing acceptance in the treatment of several functional disturbances of the urinary and intestinal tract. This new therapeutic approach offers new possibilities in the treatment of fecal incontinence (FI) by means of its possible effects on anorectal physiology.<br><br>PATIENTS AND METHODS: Fourteen patients with FI, six of whom had associated urinary disturbances, underwent permanent SNM after successful peripheral nerve evaluation tests. All had a clinical evaluation including FI grading systems (American Medical systems, AMS; Continence Grading System, CGS) and quality of life questionnaires (Fecal Incontinence Quality of Life, FIQL), and anorectal physiology tests performed before and during electrostimulation. Two patients had a lead displacement which was repositioned. Median follow-up was 14 months (range 6-48 months).<br><br>RESULTS: AMS scores decreased significantly from 101 to 67 after 24 months CGS scores from 15 to 2 after 2 months. The median number of episodes of major incontinence per 2 weeks decreased from 14 to 1 after 24 months. FIQL scores improved significantly in the nine patients tested from an overall score of 1.59 to 3.3, with improvement in all areas of the FIQL. Four of the six patients with associated urinary disturbances had a significant improvement in their symptoms. Anal resting and squeezing tone did not change significantly, nor did rectal volumetry, compliance, rectoanal inhibitory reflex, or length of the anal high-pressure zone, while 24-h rectal manometry showed inhibition of the spontaneous rectal motility complexes after meal and on awakening in the only two patients undergoing this investigation.<br><br>CONCLUSION: Although the mechanism of action of SMN is still unclear and requires further investigations, clinical results are very encouraging, confirming the role of this new and safe procedure in the treatment of FI and associated urinary disturbances.}, }
@article {pmid13677093, year = {2003}, author = {Hernández, F and Rivas, S and Avila, LF and Díaz, M and Leal, N and Martínez, L and Murcia, J and Olivares, P and Mariño, JM and López, M and Lassaletta, L and Tovar, JA}, title = {[Extensive aganglionosis. Treatment and long term results].}, journal = {Cirugia pediatrica : organo oficial de la Sociedad Espanola de Cirugia Pediatrica}, volume = {16}, number = {2}, pages = {54-57}, pmid = {13677093}, issn = {0214-1221}, mesh = {Child, Preschool ; Female ; Hirschsprung Disease/physiopathology/*therapy ; Humans ; Infant ; Infant, Newborn ; Male ; Treatment Outcome ; }, abstract = {INTRODUCTION: Extensive aganglionosis (EA) that affects the total colon (including or not part of the small intestine), shows more diagnostic problems and it is associated to higher morbidity and mortality rates than the classic cases of Hirschsprung disease (ED). This study takes into account last years cases and their results in the medium and long term.<br><br>MATERIAL AND METHODS: Between 1983 and 2000, 232 patients suffering ED have been treated. 15 out of those 232 patients showed EA. We took into consideration the diagnosis, surgical procedures, enterocolitis before and after the treatment, the surgical technique and the complications. We analyze the nutritional state and the long term result according to clinical bowel function scoring system continency Scale, considering the surgical possibilities depending on each case.<br><br>RESULTS: Two patients died due to septics complications, one of them during the neonatal period and the other one at the age of 3. Two other cases became possible candidates to an intestinal transplantation due to the extension of their disease. Five out of the 11 left patients had more than 30 cm of small intestine involved, and another five had involved less than 30 cm from ileocecal valve. The last case showed a total colonic aganglionosis with associated intestinal neuronal displasia. One case was associated with S. Ondine and another one with a 21 triosomia. Two of the patients were brothers and another patient has got a brother suffering from rectosigmoid HD. The surgical techniques used with 13 were: 8 cases using Lester Martin modification (one of them needed redo procedure because of anastomosis leak and perineal fistula), 4 Swenson procedure and one patient was treated by Ziegler's miectomy with prolongated miotomy. Nine of the patients mentioned before, lead a quite life (five L, Martin, 4 Swenson); 2 patients suffering frequent fecal retention crisis. 5 out of the 11 reviewed cases, show a weight and height p > or = 50, 2 below p50, 2 below p25, and 2 under p3.<br><br>CONCLUSION: EA represents a small percentage of Hirschsprung disease. Although Martin modification is the most widely employed technique in cases of distal ileal involvement, Swenson procedure has provided good results in the long term follow-up with few complications. Intestinal transplantation may be the only choice for long term survival in patients with near total intestinal aganglionosis. Continence improves in the follow-up but few times is normal. Nutritional state should be-controlled by a specialized team.}, }
@article {pmid12958221, year = {2003}, author = {Svenungsson, B and Burman, LG and Jalakas-Pörnull, K and Lagergren, A and Struwe, J and Akerlund, T}, title = {Epidemiology and molecular characterization of Clostridium difficile strains from patients with diarrhea: low disease incidence and evidence of limited cross-infection in a Swedish teaching hospital.}, journal = {Journal of clinical microbiology}, volume = {41}, number = {9}, pages = {4031-4037}, pmid = {12958221}, issn = {0095-1137}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Clostridioides difficile/*classification/genetics/isolation &amp; purification ; Cross Infection/epidemiology ; Diarrhea/epidemiology/*microbiology ; Female ; Hospitals, Teaching ; Humans ; Incidence ; Infant ; Male ; Middle Aged ; Polymerase Chain Reaction ; Prospective Studies ; Ribotyping ; Sweden/epidemiology ; }, abstract = {We prospectively studied the epidemiology of Clostridium difficile-associated diarrhea (CDAD) in a 900-bed hospital over the course of 12 months by PCR-ribotyping of C. difficile isolates. A total of 304 cases were diagnosed, corresponding to an overall incidence of 7/1,000 admissions, with higher rates in nephrology, hematology, and organ transplantation wards (37, 30, and 21/1,000), and 72% were classified as hospital associated (onset in hospital or onset at home but after a hospital stay within 2 months). All 382 isolates from 227 of 304 (75%) patients available for PCR-ribotyping were typeable, yielding 70 PCR-ribotypes. The three most common types comprised 30% of hospital-associated and 34% of community-associated cases, indicating import via admitted patients as a major source of C. difficile strains occurring in the hospital. Of the 227 patients studied, 38% each contributed 2 to 13 fecal samples positive for C. difficile over the course of the study period. Repeat isolates of the same PCR-ribotype as the first isolate were found in 79% of these patients and in 95% of specimens delivered within 30 days, compared to 63% of those obtained at 31 to 204 days. Nosocomial acquisition of CDAD, defined as the proportion of cases sharing C. difficile type and admitted to the same ward within 2 or 12 months, was 20% and 32% of hospital-associated cases and 14% and 23% of all cases, respectively. Thus, most CDAD cases diagnosed over the course of the study period, including those associated with hospitalization, appeared to be caused by endogenous C. difficile strains rather than by strains truly being acquired in the hospital.}, }
@article {pmid12947888, year = {2003}, author = {Macedo, G and Lopes, S and Barroso, S and Ribeiro, A and Costa-Maia, J and de Matos, N}, title = {The role of endoscopy in the management of liver transplant patients.}, journal = {Transplantation proceedings}, volume = {35}, number = {3}, pages = {1133}, doi = {10.1016/s0041-1345(03)00338-5}, pmid = {12947888}, issn = {0041-1345}, mesh = {Anemia ; Cholestasis ; Deglutition Disorders ; Dyspepsia ; Endoscopy, Digestive System/*methods ; Hematemesis ; Humans ; Liver Transplantation/*physiology ; Melena ; Postoperative Complications/classification ; Retrospective Studies ; Vomiting ; }, }
@article {pmid12909563, year = {2003}, author = {Lemahieu, WP and Maes, BD and Ghoos, Y and Rutgeerts, P and Verbeke, K and Vanrenterghem, Y}, title = {Measurement of hepatic and intestinal CYP3A4 and PGP activity by combined po + iv [14C]erythromycin breath and urine test.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {285}, number = {3}, pages = {G470-82}, doi = {10.1152/ajpgi.00028.2003}, pmid = {12909563}, issn = {0193-1857}, mesh = {ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism/urine ; Administration, Oral ; *Breath Tests ; Carbon Radioisotopes/analysis ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System/*metabolism/urine ; Erythromycin/*administration &amp; dosage ; Feces/chemistry ; Female ; Gastric Acid/metabolism ; Gastric Emptying ; Humans ; Injections, Intravenous ; Intestinal Mucosa/*metabolism ; Itraconazole/pharmacology ; Kidney Transplantation ; Liver/*metabolism ; Male ; Postoperative Period ; Reference Values ; }, abstract = {The aim of the present study was to develop a test for measuring hepatic and intestinal removal of cytochrome p-450 3A4 (CYP3A4)- and P-glycoprotein (PGP)-dependent xenobiotics that would be applicable for clinical use in humans. Orally and intravenously administered [N-methyl-14C]erythromycin was used for evaluation of 14C-labeled excretion dynamics in breath and urine. Simultaneous breath and urine test measurements were performed in 32 healthy volunteers and in 23 renal transplant recipients. Mathematical analysis of the excretion rate of labeled CO2 in breath and labeled carbon in urine resulted in 1). separation of both CYP3A4 and PGP activity in the liver and the intestinal mucosa and 2). numerical calculation of the dynamics of the different processes. The test was sufficiently sensitive to detect theoretically predicted process-specific pharmacological modulations by different drugs in healthy volunteers and after recent renal transplantation. It is concluded that the combined oral and intravenous erythromycin breath and urine test is a reliable and noninvasive test to measure phenotypic intestinal and hepatic CYP3A4 and PGP activity and may be a promising tool for prediction of drug interactions and dose adjustment of many pharmacotherapeutics in clinical practice, e.g., immunosuppressive agents after renal transplantation.}, }
@article {pmid12903888, year = {2003}, author = {Rovera, GM and Schoen, RE and Goldbach, B and Janson, D and Bond, G and Rakela, J and Graham, TO and O'Keefe, S and Abu-Elmagd, K}, title = {Intestinal and multivisceral transplantation: dynamics of nutritional management and functional autonomy.}, journal = {JPEN. Journal of parenteral and enteral nutrition}, volume = {27}, number = {4}, pages = {252-259}, doi = {10.1177/0148607103027004252}, pmid = {12903888}, issn = {0148-6071}, mesh = {Adult ; Anthropometry ; Body Weight ; Energy Intake ; Enteral Nutrition ; Female ; Humans ; Intestinal Absorption ; Intestinal Diseases/*surgery ; Intestines/*transplantation ; Liver Transplantation ; Male ; Middle Aged ; Nutritional Status ; *Nutritional Support ; Pancreas Transplantation ; Parenteral Nutrition, Total ; Postoperative Care ; Serum Albumin/analysis ; Stomach/transplantation ; Time Factors ; Transplantation, Homologous ; }, abstract = {OBJECTIVE: The objective of this study was to describe the dynamics of nutrition management of intestinal transplant recipients and allograft functional autonomy.<br><br>METHODS: Intestinal absorptive functions and recipient nutritional status were monitored during the 12-month study period. Absorption was evaluated with D-xylose absorption and fecal fat excretion. Indices for nutrition were body weight, anthropometric measures, and serum albumin.<br><br>RESULTS: Before transplant, all patients were total parenteral nutrition (TPN) dependent and well nourished. By the first postoperative month, all 22 recipients were tolerating enteral feeding. By 3 months, all recipients had begun oral feeding, with 13 off TPN and 7 off enteral feeds. By 6 months, 16 recipients were off TPN, and by the end of the 12th month, 17 (77%) were free of TPN. Although all 22 recipients were completely weaned off TPN during the first posttransplant year, 10 required temporary reinstitution of therapy at different points. Full nutritional autonomy was achieved at 3 months by 3 recipients, at 6 months by 8 recipients, and at 12 months by 12 (55%) recipients.<br><br>CONCLUSIONS: These results reflect our early experience that led to surgical refinement of the operation and evolution of the recipient postoperative management. Nonetheless, even in this initial cohort, most of the engrafted intestines restored the recipient nutritional autonomy, and all survivors remained well nourished.}, }
@article {pmid12900335, year = {2003}, author = {Zhang, Y and Zanotti, I and Reilly, MP and Glick, JM and Rothblat, GH and Rader, DJ}, title = {Overexpression of apolipoprotein A-I promotes reverse transport of cholesterol from macrophages to feces in vivo.}, journal = {Circulation}, volume = {108}, number = {6}, pages = {661-663}, doi = {10.1161/01.CIR.0000086981.09834.E0}, pmid = {12900335}, issn = {1524-4539}, support = {P01-HL22633/HL/NHLBI NIH HHS/United States ; P01-HL59407/HL/NHLBI NIH HHS/United States ; P50-HL70128/HL/NHLBI NIH HHS/United States ; R01-HL55323/HL/NHLBI NIH HHS/United States ; R01-HL63768/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Apolipoprotein A-I/*biosynthesis/genetics ; Bile Acids and Salts/analysis ; Biological Transport/*physiology ; Cell Line ; Cholesterol/analysis/*metabolism/pharmacokinetics ; Feasibility Studies ; *Feces/chemistry ; Foam Cells/cytology/metabolism/transplantation ; Gene Transfer Techniques ; Lipoproteins, LDL/metabolism ; Liver/chemistry/metabolism ; Macrophages/cytology/*metabolism/transplantation ; Male ; Mice ; Mice, Inbred C57BL ; Tritium ; }, abstract = {BACKGROUND: Abundant data indicate that overexpression of apolipoprotein A-I (apoA-I) in mice inhibits atherosclerosis. One mechanism is believed to be promotion of reverse cholesterol transport, but no direct proof of this concept exists. We developed a novel approach to trace reverse transport of labeled cholesterol specifically from macrophages to the liver and feces in vivo and have applied this approach to investigate the ability of apoA-I overexpression to promote macrophage-specific reverse cholesterol transport.<br><br>METHOD AND RESULTS: J774 macrophages were loaded with cholesterol by incubation with acetylated LDL, labeled with 3H-cholesterol, and then injected intraperitoneally into mice. Plasma and feces were collected at 24 hours and 48 hours, when mice were exsanguinated, tissues were harvested, and all were analyzed for tracer counts. 3H-cholesterol was found in the plasma, liver, and feces. For apoA-I overexpression, mice were injected intravenously with apoA-I adenovirus (1011 particles per animal) 3 days before labeled macrophages were injected. ApoA-I overexpression led to significantly higher 3H-cholesterol in plasma, liver, and feces. The amount of 3H-tracer in the liver was 35% higher (P<0.05) and the 3H-tracer excreted into feces over 48 hours was 63% higher (P<0.05) in apoA-I-expressing mice than in control mice.<br><br>CONCLUSIONS: Injection of 3H-cholesterol-labeled macrophage foam cells is a method of measuring reverse cholesterol transport specifically from macrophages to feces in vivo, and apoA-I overexpression promotes macrophage-specific reverse cholesterol transport.}, }
@article {pmid12874583, year = {2003}, author = {Witzigmann, H and Max, D and Uhlmann, D and Geissler, F and Schwarz, R and Ludwig, S and Lohmann, T and Caca, K and Keim, V and Tannapfel, A and Hauss, J}, title = {Outcome after duodenum-preserving pancreatic head resection is improved compared with classic Whipple procedure in the treatment of chronic pancreatitis.}, journal = {Surgery}, volume = {134}, number = {1}, pages = {53-62}, doi = {10.1067/msy.2003.170}, pmid = {12874583}, issn = {0039-6060}, mesh = {Adult ; Chronic Disease ; Female ; Humans ; Male ; Middle Aged ; Pain Measurement ; Pancreas/physiopathology ; Pancreatectomy/*methods ; *Pancreaticoduodenectomy ; Pancreatitis/physiopathology/*surgery ; Postoperative Complications ; Prospective Studies ; Quality of Life ; }, abstract = {BACKGROUND: There is no consensus in the surgical management of chronic pancreatitis (cP) as to whether techniques preserving the duodenum are superior to pancreatoduodenectomy. This prospective study compared the outcome of standard pancreatoduodenectomy (PD) and duodenum-preserving pancreatic head resection (DPPHR) in treatment of selected patients with cP.<br><br>METHODS: Inclusion criteria for this prospective controlled, nonrandomized study were patients suffering from cP centered in the head and with severe pain. Seventy consecutive patients underwent DPPHR (n = 38) or, if there was suspicion of malignancy, classic PD (n = 32). A multidimensional, psychometric questionnaire was used to measure the quality of life (QoL). QoL was compared with that of the general German population. Pain intensity was evaluated on the basis of the frequency of pain attacks, analgesic medication, and self-assessed pain score. Assessment of endocrine and exocrine function as well as nutritional status included oral glucose tolerance test, fecal elastase, stool frequency, and body mass index. The median follow-up was 34 months.<br><br>RESULTS: Multiple clinical characteristics did not differ between the two groups except for age (P =.04), the tumor marker carbohydrate antigen 19-9 (P =.02), and the parameter suspicion of malignancy. There was no hospital mortality. Surgical morbidity was 19% in the PD group and 8% in the DPPHR group (P =.60). PD resulted in a longer median hospital stay than DPPHR (19 vs 15 days, P =.04). Complications of adjacent organs were definitively treated in 100% after PD and in 97% after DPPHR. Postoperative pain intensity as self-assessed by the patients was significantly less in the DPPHR group (P <.001), whereas the frequency of acute episodes (P =.27) and analgesic medication (P =.43) did not differ between the two groups. After surgery, symptom and functional scales of the DPPHR group were significantly better than those in the PD group and were similar to those of the overall German population. No significant difference was found between the two groups with regard to endocrine and exocrine function. Postoperative increase of body mass index was significantly higher in the DPPHR group (P <.001).<br><br>CONCLUSIONS: DPPHR provides better results in the treatment of cP than PD in terms of QoL, pain intensity as self-assessed by the patients, nutritional status, and length of hospital stay.}, }
@article {pmid12850500, year = {2003}, author = {Miura, D and Miura, Y and Yagasaki, K}, title = {Hypolipidemic action of dietary resveratrol, a phytoalexin in grapes and red wine, in hepatoma-bearing rats.}, journal = {Life sciences}, volume = {73}, number = {11}, pages = {1393-1400}, doi = {10.1016/s0024-3205(03)00469-7}, pmid = {12850500}, issn = {0024-3205}, mesh = {Animals ; Antioxidants/pharmacology ; Cell Division/drug effects ; Cholesterol/blood ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Cholesterol, VLDL/blood ; Dose-Response Relationship, Drug ; Fruit/*chemistry ; Hypolipidemic Agents/*pharmacology ; Lipid Peroxides/blood ; Lipids/analysis ; Liver/chemistry ; Liver Neoplasms, Experimental/*blood/drug therapy/pathology ; Male ; Neoplasm Metastasis/prevention &amp; control ; Neoplasm Transplantation ; Rats ; Resveratrol ; Stilbenes/*pharmacology/therapeutic use ; Thiobarbituric Acid Reactive Substances/analysis ; Triglycerides/blood ; Tumor Cells, Cultured ; Vitis/*chemistry ; Wine/*analysis ; }, abstract = {Resveratrol is an antioxidant present in grapes and their related products. We investigated whether dietary resveratrol could inhibit the proliferation and metastasis of tumors and hyperlipidemia in Donryu rats subcutaneously implanted with an ascites hepatoma cell line of AH109A. By feeding 10 or 50 ppm resveratrol in the diet to hepatoma-bearing rats for 20 days, solid tumor growth and metastasis tended to be suppressed dose-dependently. Resveratrol (50 ppm) significantly suppressed the serum lipid peroxide level, indicating its antioxidative properties or those of its metabolite(s) in vivo. Resveratrol dose-dependently suppressed both the serum triglyceride and very-low-density lipoprotein + low-density lipoprotein (VLDL + LDL)-cholesterol levels. The hypocholesterolemic action of resveratrol is attributed, at least in part, to an increased excretion of neutral sterols and bile acids into feces. These results suggest that dietary resveratrol is hypolipidemic with a tendency for anti-tumor-growth and anti-metastasis effects in hepatoma-bearing rats.}, }
@article {pmid12848727, year = {2003}, author = {Queipo, JA and Broseta, E and Santos, M and Sánchez-Plumed, J and Budía, A and Jiménez-Cruz, F}, title = {Mycobacterial infection in a series of 1261 renal transplant recipients.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {9}, number = {6}, pages = {518-525}, doi = {10.1046/j.1469-0691.2003.00532.x}, pmid = {12848727}, issn = {1198-743X}, mesh = {Adult ; Female ; Follow-Up Studies ; Graft Rejection/etiology ; Humans ; Immunosuppression Therapy/*adverse effects ; Kidney/microbiology/physiopathology ; *Kidney Transplantation ; Male ; Middle Aged ; *Mycobacterium ; Mycobacterium Infections/*etiology/physiopathology ; Retrospective Studies ; }, abstract = {OBJECTIVE: To describe the incidence and clinical characteristics of mycobacterial infection in renal transplant recipients.<br><br>METHODS: We retrospectively analyzed the cases of mycobacterial infection in a series of 1261 renal transplants carried out in our Unit of Renal Transplantation from 1980 to 2000. Demographic parameters and clinical antecedents such as age, cause of end-stage renal disease, time of follow-up of the graft, previous renal function and type of immunosuppression were considered. Moreover, the clinical onset, diagnostic tools, treatment policy and evolution were studied. The pathogenesis of the different types of mycobacteria isolated was also analyzed. Diagnosis was made with the Ziehl-Neelsen staining method. Culture was performed by the conventional L&#xf6;wenstein-Jensen method and the Bactec-460 radiometric method.<br><br>RESULTS: We found mycobacterial infection in 27 patients (2.1%), due to Mycobacterium tuberculosis in 20 cases, M. kansasii in five patients, and M. fortuitum in two patients. The mean elapsed time from the renal transplant was 20.5 months; the infection appeared in 18 patients during the first eight months after transplantation. The clinical onset was pulmonary infection in 17 cases (12 M. tuberculosis and five M. kansasii); five had urinary symptoms (three M. tuberculosis and two M. fortuitum); three cases of M. tuberculosis infection had abdominal symptoms; another one began with a perineal tuberculous abscess; the rest of the patients were asymptomatic. The types of specimen on which microbiological identification was carried out were, in decreasing order: sputum and/or bronchial washing/pleural aspiration, urine, feces, gastric and peritoneal fluids, bone marrow and blood. The first-line drug isoniazid had the highest resistance index in the susceptibility test. Clinical dissemination was observed in eight patients, four of whom died. Another three patients had a significant impairment in renal function, and in one of these patients an allograft nephrectomy was necessary due to a severe septic syndrome.<br><br>CONCLUSIONS: Mycobacterial infection, mainly by M. tuberculosis, has an important impact on kidney transplant recipients, particularly during the first year after surgery. Diagnosis often presents some difficulties, and a delay in treatment represents a determinant factor for the evolution, with a risk of death or permanent damage in renal function. Therefore, early diagnosis is mandatory. When the Mantoux reaction is positive, antituberculous prophylaxis seems advisable.}, }
@article {pmid12826224, year = {2003}, author = {Straub, B and Müller, M and Heicappell, R and Schrader, M and Goessl, C and Miller, K}, title = {Hyperphosphaturia after kidney transplantation in syngeneic rats: effects on nephrocalcinosis and bone metabolism?.}, journal = {Transplantation proceedings}, volume = {35}, number = {4}, pages = {1575-1580}, doi = {10.1016/s0041-1345(03)00526-8}, pmid = {12826224}, issn = {0041-1345}, mesh = {Adenosine ; Allopurinol ; Animals ; Bone and Bones/*metabolism ; Calcinosis/*etiology ; Disease Models, Animal ; Glutathione ; Insulin ; Kidney Diseases/*etiology ; Kidney Transplantation/*adverse effects/physiology ; Male ; Nephrectomy ; Organ Preservation ; Organ Preservation Solutions ; Phosphates/*urine ; Raffinose ; Rats ; Rats, Inbred Lew ; Tissue and Organ Harvesting ; Transplantation, Isogeneic ; Urinalysis ; }, abstract = {BACKGROUND: Studies on kidney transplantation have thus far mainly dealt with surgical techniques, immunology, and transplant tolerance. Disturbed mineral metabolism after renal denervation has not received much attention. Basic physiological research in short-term experiments has shown that experimental renal denervation in rats leads to parathormone (PTH)-independent hyperphosphaturia (HPU). HPU and other metabolic complications also have been described after clinical kidney transplantation. Furthermore, there is an unexpected increase in the risk of bone fracture. However, these studies have examined an organism pre-damaged with regard to the parathyroid and immunosuppression. Experimental investigations in syngeneic rats were performed to see whether HPU also occurs after transplantation and thus after denervation and which target organs are involved.<br><br>METHODS: Thirty-six male Lewis rats subjected to laparotomy (n = 12), unilateral nephrectomy (n = 12), or unilateral transplantation and bilateral nephrectomy (n = 12) were observed for 18 weeks.<br><br>RESULTS: Animals that underwent transplantation had a significant loss of phosphate in the urine not associated with decreased calcium, phosphate, or magnesium in bone. Stability test showed no deterioration, despite a slight increase in the bone parameters of alkaline phosphatase, cyclic AMP, and hydroxyproline with unchanged calciotropic hormones. Nephrocalcinosis was not observed. Parallel to HPU, there was a compensatory reduction in fecal phosphate excretion.<br><br>CONCLUSIONS: The loss of phosphate after clinical kidney transplantation in the predamaged parathyroid hormone control system as well as immunosuppression and a surprising increase in the incidence of bone fractures may be explained by the denervation-related loss of phosphate. The lack of intestinal counter-regulation could be an important pathomechanism.}, }
@article {pmid12794571, year = {2003}, author = {Rongen, MJ and Uludag, O and El Naggar, K and Geerdes, BP and Konsten, J and Baeten, CG}, title = {Long-term follow-up of dynamic graciloplasty for fecal incontinence.}, journal = {Diseases of the colon and rectum}, volume = {46}, number = {6}, pages = {716-721}, doi = {10.1007/s10350-004-6645-7}, pmid = {12794571}, issn = {0012-3706}, mesh = {Adolescent ; Adult ; Aged ; *Electric Stimulation Therapy ; Electrodes, Implanted ; Fecal Incontinence/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle Contraction ; Muscle, Skeletal/*transplantation ; }, abstract = {PURPOSE: Graciloplasty has been used as a treatment for end-stage fecal incontinence since 1946. Electric stimulation with an implantable pulse generator has existed for 15 years. The gracilis muscle is wrapped around the anal canal and stimulated by intramuscular electrodes connected with an implantable pulse generator. Initial reports have been promising, but long-term results have not been presented to date.<br><br>METHODS: Data of 200 consecutive patients with a follow-up of at least two years were analyzed in a prospective manner from 1986 until 1999.<br><br>RESULTS: The overall success rate was 72 percent. In patients with fecal incontinence caused by trauma, the rate was 82 percent. Once continent, patients remained continent after a median follow-up of 261 (standard deviation, 132) weeks. Median survival of the implantable pulse generator until battery expiration was 405 weeks. Disturbed evacuation remained a problem in 16 percent of all patients. Complications were frequent but treatable.<br><br>CONCLUSION: Dynamic graciloplasty is a good, cost-effective treatment for fecal incontinence with results lasting for a median of more than five years.}, }
@article {pmid12791022, year = {2001}, author = {Rongen, MJ and Adang, EM and van der Hoop, AG and Baeten, CG}, title = {One-step vs two-step procedure in dynamic graciloplasty.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {3}, number = {1}, pages = {51-57}, doi = {10.1046/j.1463-1318.2001.00161.x}, pmid = {12791022}, issn = {1462-8910}, abstract = {OBJECTIVE: Dynamic graciloplasty, a proven treatment for end-stage faecal incontinence, requires transposition of the gracilis muscle around the anal canal and implantation of a pulse generator and intramuscular electrodes. In view of the risk of infection around the implanted material the implantation was initially not performed in combination with the perineal procedure but 6 weeks later. Sparing the patients an extra operation, however, might be justified if morbidity is not increased. This study aimed to compare the combined single-stage with the two-stage procedures.<br><br>PATIENTS AND METHODS: Two groups of 13 patients were admitted to this prospective, matched control study according to waiting list ranking. They were matched for age, gender and aetiology. Group I had transposition and transplantation combined, group II underwent these procedures separately with a 6-week interval. Continence, manometry, stimulation parameters, quality of life results and adverse events were recorded.<br><br>RESULTS: After a mean 521-day follow up infection rates were comparable in both groups, as were continence rates, morbidity, anal manometry, stimulation parameters and quality of life.<br><br>CONCLUSION: Outcome, morbidity and quality of life seem to be comparable. A single procedure avoids the need for an extra admission and operation, so the one-stage approach should be the standard procedure in dynamic graciloplasty.}, }
@article {pmid12756590, year = {2003}, author = {García-Olmo, D and García-Arranz, M and García, LG and Cuellar, ES and Blanco, IF and Prianes, LA and Montes, JA and Pinto, FL and Marcos, DH and García-Sancho, L}, title = {Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn's disease: a new cell-based therapy.}, journal = {International journal of colorectal disease}, volume = {18}, number = {5}, pages = {451-454}, pmid = {12756590}, issn = {0179-1958}, mesh = {Adult ; Crohn Disease/*complications ; Female ; Humans ; *Lipectomy ; Rectovaginal Fistula/etiology/*therapy ; Secondary Prevention ; Stem Cell Transplantation/*methods ; Transplantation, Autologous ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Rectovaginal fistulas in patients with Crohn's disease are difficult to resolve, and surgical failure is very frequent. Recent studies have shown that adult stem cells extracted from certain tissues, such as adipose tissue, can develop into different tissues, such as muscle.<br><br>PATIENT AND METHODS: We report here the case of a young patient with Crohn's disease who had a recurrent rectovaginal fistula that was treated by autologous stem-cell transplantation with a lipoaspirate as the source of stem cells.<br><br>RESULTS: Although Crohn's disease is the worst condition for a surgical approach in cases of rectovaginal fistula, we observed good closure. Since the surgical procedure 3 month ago the patient has not experienced vaginal flatus or fecal incontinence through her vagina. Thus our treatment seems to be effective.<br><br>CONCLUSION: Cell transplantation to overcome healing problems is a new surgical tool, and careful evaluation of this new modality may provide an opportunity to define a new era in the treatment of surgical challenges associated with healing disorders. Ethical and safety items do not seem to be critical problems using autologous stem cells.}, }
@article {pmid12756051, year = {2003}, author = {Fridell, JA and Mazariegos, GV and Orenstein, D and Sindhi, R and Reyes, J}, title = {Liver and intestinal transplantation in a child with cystic fibrosis: a case report.}, journal = {Pediatric transplantation}, volume = {7}, number = {3}, pages = {240-242}, doi = {10.1034/j.1399-3046.2003.00064.x}, pmid = {12756051}, issn = {1397-3142}, mesh = {Cystic Fibrosis/*complications ; Humans ; Infant ; Intestinal Obstruction/surgery ; Intestine, Small/*transplantation ; Liver Failure/etiology/surgery ; *Liver Transplantation ; Male ; Meconium ; Short Bowel Syndrome/etiology/surgery ; }, abstract = {Cystic fibrosis (CF) is an inherited disorder that presents as a multisystem disease with meconium ileus being the presenting symptom in 20% of patients. Approximately half of these patients present with complicated meconium ileus mandating early surgical intervention, potentially resulting in short gut syndrome. Although liver transplantation in children with CF has been described, this is the first report of a combined liver and small bowel transplant in a recipient with CF. A 7-month-old boy with CF presented with short bowel syndrome following extensive small bowel resection for meconium ileus and progressive cholestatic liver failure from intravenous hyperalimentation. He underwent combined liver and small intestinal transplant. He was discharged home three weeks post-transplant on enteral feeds with supplemental intravenous fluid. He has had routine protocol small bowel allograft biopsies with no documented rejection episodes. He has been treated for minor respiratory infections without major sequelae. Improvements in pulmonary therapy have impacted on the survival in the CF population to the point where the need for multiorgan transplantation will be increased in the future. Extrapolating from the excellent experience of liver transplantation in children with CF, early liver and small intestinal multivisceral transplantation, if indicated, can be performed safely in children with CF.}, }
@article {pmid12750951, year = {2003}, author = {Farid, M and Moneim, HA and Mahdy, T and Omar, W}, title = {Augmented unilateral gluteoplasty with fascia lata graft in fecal incontinence.}, journal = {Techniques in coloproctology}, volume = {7}, number = {1}, pages = {23-8; discussion 28}, doi = {10.1007/s101510300004}, pmid = {12750951}, issn = {1123-6337}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; *Digestive System Surgical Procedures ; Fascia Lata/*transplantation ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Manometry ; }, abstract = {BACKGROUND: This study was undertaken to evaluate the results of augmented unilateral gluteoplasty with fascia lata graft in patients with fecal incontinence due to congenital or neurologic disorders.<br><br>METHODS: Between January 2000 and January 2001, we performed a prospective study of 11 patients with longstanding fecal incontinence (stage C3 according to Pescatori scoring system for fecal incontinence). The patients included one girl and 10 boys aged 5-19 years who had already undergone Swenson's operation for congenital megacolon (7 patients) or abdominoperineal pull-through for high imperforate anus (4 patients). Preoperative anorectal manometric studies (maximum resting pressure, maximum squeeze pressure, rectoanal inhibitory reflex and functional anal canal length), saline enema test and magnetic resonance imaging (MRI) studies were done. Unilateral gluteoplasty augmented with fascia lata graft was wrapped around the anal canal. Biofeedback retraining was started at the beginning of the fourth postoperative week. Patients were followed both objectively and subjectively for about 6-18 months.<br><br>RESULTS: Eight of 11 patients (72.7%) were clinically improved, as shown by the change in incontinence score (p=0.01). this was confirmed by the significant changes in manometric studies, functional anal canal length, rectoanal inhibitory reflex and saline enema test. MRI done one month postoperatively showed disruption in one patient.<br><br>CONCLUSIONS: Unilateral gluteoplasty augmented with fascia lata graft leads to encouraging results in patients with end-stage anal incontinence due to irreversible damage to anal sphincter with less incidence of morbidity that could be related to tension on either the muscle flap or its neurovascular bundle.}, }
@article {pmid12748274, year = {2003}, author = {Murono, K and Hirano, Y and Koyano, S and Ito, K and Fujieda, K}, title = {Molecular comparison of bacterial isolates from blood with strains colonizing pharynx and intestine in immunocompromised patients with sepsis.}, journal = {Journal of medical microbiology}, volume = {52}, number = {Pt 6}, pages = {527-530}, doi = {10.1099/jmm.0.05076-0}, pmid = {12748274}, issn = {0022-2615}, mesh = {Adolescent ; Bacteremia/*microbiology ; Bacteria/classification/*genetics/isolation &amp; purification ; Child ; Child, Preschool ; Electrophoresis, Gel, Pulsed-Field ; Feces/microbiology ; Female ; Genotype ; Humans ; *Immunocompromised Host ; Infant ; Intestines/*microbiology ; Male ; Pharynx/*microbiology ; }, abstract = {Most causative organisms of sepsis in immunocompromised patients are the same species as those that colonize their own nasopharynx or intestinal tract. To determine whether the strains recovered from blood originate mainly from patients' own flora, isolates from blood and throat and/or stool were investigated by genomic analyses. Surveillance cultures of throat and stool were taken prospectively from cancer patients being treated with intensive chemotherapy followed by haematopoietic stem-cell transplantation. In those cases of sepsis in which the isolate from blood was the same species as that from the throat and/or stool, the genomic profiles of the isolates were compared by PFGE. Ten cases of blood culture-positive sepsis were documented in six of 14 subjects during a 2 year period; isolates of Pseudomonas aeruginosa, Staphylococcus epidermidis, Enterococcus sp., viridans streptococci and Fusobacterium sp. were recovered from blood. In five of seven cases in which the blood isolate was the same species as that from the throat or stool, the genotypes of the isolates from both sites were identical. In the majority of immunocompromised patients, the causative organisms of bloodstream infections originated mainly from their own flora.}, }
@article {pmid12708176, year = {2003}, author = {Ben Salah, D and Besbes, M and Boutiba, I and Greco, A and Ghozzi, R and Mahjoubi, F and Ben Rejeb, S and Hammami, A and Ben Hassen, A}, title = {[Enterococcus faecalis: a multicenter study on antibiotic resistance].}, journal = {La Tunisie medicale}, volume = {81}, number = {2}, pages = {109-112}, pmid = {12708176}, issn = {0041-4131}, mesh = {Amoxicillin/pharmacology ; Anti-Bacterial Agents/*pharmacology ; Blood/microbiology ; Chloramphenicol Resistance ; Data Interpretation, Statistical ; *Drug Resistance, Bacterial ; Enterococcus faecalis/*drug effects/isolation &amp; purification ; Erythromycin/pharmacology ; Feces/microbiology ; Gentamicins/pharmacology ; Humans ; Microbial Sensitivity Tests ; Penicillin Resistance ; Penicillins/pharmacology ; Tetracycline Resistance ; Urine/microbiology ; Vancomycin/pharmacology ; Vancomycin Resistance ; }, abstract = {676 E. faecalis strains were listed over a period of 2 years from the Charles Nicolle hospital of Tunis (167 strains), the Habib Bourguiba hospital of Sfax (350 strains) and the National Centre of Bone marrow Transplantation of Tunis (159 strains). Antibiotic sensibility study was realized by the method of the antibiogram, E-test method and the search of penicillinase by cefinase. E. faecalis resulted essentially from services of onco-haematology (24%), external consultations (23%), surgery (18%) and medicine (15%). These strains were isolated especially from urines (54%), coprocultures (15%), bloodcultures (11%) and from pus (9%). Resistance acquired with these strains is raised for erythromycin, tetracyclin and chloramphenicol (81% to 86%), followed by high level resistance to gentamicine (37%). 0.1% of E. faecalis strains have a low level resistance to amoxicillin without production of penicillinase. No resistance to vancomycin was observed.}, }
@article {pmid12704920, year = {2002}, author = {Drücke, D and Lehnhardt, M and Steinsträsser, L and Langer, S and Homann, HH and Steinau, HU}, title = {[Secondary reconstruction after burns of the anogenital area].}, journal = {Kongressband. Deutsche Gesellschaft fur Chirurgie. Kongress}, volume = {119}, number = {}, pages = {733-735}, pmid = {12704920}, issn = {1868-1050}, mesh = {Anal Canal/*injuries/surgery ; Burns/*surgery ; Cicatrix/surgery ; Fecal Incontinence/surgery ; Female ; Genitalia/*injuries/surgery ; Humans ; Male ; Postoperative Complications/*surgery ; Reoperation ; Skin Transplantation ; Surgical Flaps ; }, abstract = {The incidence of burns of the genitalia and peri-anal region which may cause a reconstructive intervention is very low. In the most cases the use of split thickness skin grafts yields a sufficient permanent wound closure. Upcoming problems such as painful scare formation require a reconstructive intervention (Z-plasty, full thickness skin grafting, pedicled flaps etc.). In case that the anal sphincter is involved with the consequence of incontinence or major damage of the genitalia occurred, sophisticated operative solutions are necessary.}, }
@article {pmid12696109, year = {2003}, author = {Heim, A and Ebnet, C and Harste, G and Pring-Akerblom, P}, title = {Rapid and quantitative detection of human adenovirus DNA by real-time PCR.}, journal = {Journal of medical virology}, volume = {70}, number = {2}, pages = {228-239}, doi = {10.1002/jmv.10382}, pmid = {12696109}, issn = {0146-6615}, mesh = {Adenovirus Infections, Human/*diagnosis/virology ; Adenoviruses, Human/classification/genetics/*isolation &amp; purification ; Adult ; Base Sequence ; Bone Marrow Transplantation/adverse effects ; Capsid Proteins/genetics ; Child ; DNA Primers ; DNA, Viral/*analysis ; Humans ; Molecular Sequence Data ; Polymerase Chain Reaction/*methods ; Sensitivity and Specificity ; *Taq Polymerase ; Time Factors ; Viral Load ; Viremia/virology ; }, abstract = {Rapid diagnosis of human adenovirus (HAdV) infections was achieved by PCR in the recent years. However, conventional PCR has the risk of carry-over contamination due to open handling with its products, and results are only qualitative. Therefore, a quantitative "real-time" PCR with consensus primer and probe (dual fluorescence labelled, "TaqMan") sequences for a conserved region of the hexon gene was designed and evaluated. Real-time PCR detected all 51 HAdV prototypes. Sensitivity of the assay was <or=15 copies/run and the linear range of quantitation 1.5 x 10(1) to 1.5 x 10(8) copies/run. TaqMan PCR gave identical results compared to an established conventional one-step PCR protocol in 218 (38 positive and 180 negative) of 234 clinical samples including blood, serum, eye swabs, and feces, and had divergent results in 16 samples (15 positive only in TaqMan PCR, all with low copy numbers, and one positive only in conventional PCR), indicating a higher sensitivity of TaqMan PCR. Adenovirus viremia was detected by TaqMan PCR in 4 of 27 (14.8%) paediatric and 8 of 93 (8.6%) adult stem cell transplant recipients but only in 5 of 306 healthy controls (blood donors, 1.6%). Virus loads of pediatric patients (median 1.7 x 10(5)) were significantly higher than in adult patients (median 2.3 x 10(3)) and than in controls (all samples <or=1.7 x 10(3) copies/ml). A few immunosuppressed children had very high virus loads (up to 1.1 x 10(10) copies/ml), which were associated with symptoms of disseminated disease. In conclusion, real-time PCR is a sensitive and quantitative procedure for the detection of adenovirus infections.}, }
@article {pmid12692049, year = {2003}, author = {Genton, L and Raguso, CA and Berney, T and Hans, DB and Morel, P and Pichard, C}, title = {Four year nutritional follow up after living related small bowel transplantation between monozygotic twins.}, journal = {Gut}, volume = {52}, number = {5}, pages = {659-662}, pmid = {12692049}, issn = {0017-5749}, mesh = {Adolescent ; Body Composition/physiology ; Body Height/physiology ; Bone Density/physiology ; Calorimetry ; Energy Metabolism/physiology ; Follow-Up Studies ; Humans ; Intestinal Absorption/physiology ; Intestine, Small/*transplantation ; Male ; Minerals/blood ; Nutritional Status/*physiology ; Parenteral Nutrition/methods ; *Twins, Monozygotic ; Vitamins/blood ; Weight Gain/physiology ; }, abstract = {While small bowel transplantation (SBTX) may allow parenteral nutrition independence in the case of short bowel syndrome, its effects on body composition and growth are unclear. For the first time, a paediatric living related SBTX was performed between monozygotic twins. This case report describes their four year nutritional follow up. The 13 year old recipient and his healthy brother underwent measurements of body composition by 50 kHz bioimpedance analysis and bone mineral density of the femoral neck and total femur by dual energy x ray absorptiometry. Xylose tests and measurements of faecal fat evaluated gut absorption. All tests were performed before and after SBTX. Body weight increased from 34.7 to 51.9 kg in the recipient and from 45.0 to 53.2 kg in the donor within four years. The recipient caught up with the height and fat free mass of his brother within two years. Fat mass, and total femur and femoral neck densities are still lower in the recipient than in the donor four years after SBTX (-1.2 kg, -0.087 g/cm(2), -0.035 g/cm(2)). The xylose test of the recipient was still abnormally low after four years (1.37 mmol/l) and faecal fat was high until two years after SBTX (March 2001: 12 g/24 h). The donor always showed normal xylose tests and faecal fat, except for one episode of high faecal fatty acids about 10 months after SBTX. SBTX improved the nutritional state and growth of the graft recipient although body composition, femoral bone mineral densities, and intestinal absorption had not completely normalised after four years.}, }
@article {pmid12681116, year = {2003}, author = {Casanovas Taltavull, T and Vallejo Blanxart, G and Herdman, M and Verge Monedero, JM and Tremosa Llurba, G and Rodríguez Fariña, E and Ramos Rubio, E and Baliellas Comellas, C and Figueras Felip, J and Menchón Magriñá, JM and Casais Alvarez, LA}, title = {[Transcultural adaptation of the Liver Disease Quality of Life instrument (LDQOL 1.0) for its use in the Spanish population].}, journal = {Gastroenterologia y hepatologia}, volume = {26}, number = {4}, pages = {234-244}, pmid = {12681116}, issn = {0210-5705}, mesh = {Cross-Cultural Comparison ; Cultural Characteristics ; Humans ; Language ; Latin America ; Liver Diseases/*psychology ; Patient Acceptance of Health Care ; Pilot Projects ; *Quality of Life ; Reproducibility of Results ; Sensitivity and Specificity ; *Severity of Illness Index ; Spain ; *Surveys and Questionnaires ; }, abstract = {Instruments of health-related quality of life (HRQOL) help us to interpret the results of treatments and health interventions. In Spain there is no HRQOL instrument specifically designed for use in patients with liver disease or to measure the effect of interventions such as liver transplantation. The Liver Disease Quality of Life (LDQOL 1.0) questionnaire is an American instrument developed for use in these patients. The aim of this study was to produce an appropriate version of this questionnaire for use in Spain. Cultural adaptation was performed in 3 phases: a) modification for use in Spain of a Hispanic version of this questionnaire supplied by the original authors; b) back-translation to English of a new version of the questionnaire and comparison with the original version in English, and c) a pilot test in a small sample of patients. In the first phase consisting of revision of the Hispanic version, the changes were mainly linguistic due to cultural and idiomatic differences. The validated Spanish version of the SF-36 was directly incorporated and items that could be of interest to local investigators were added. Few changes were made in the second phase of the process: changes involved an item on the appearance of feces and another item on taking naps. In the final phase, various changes suggested by the patients were introduced. Before applying the new version of the LDQOL 1.0 in clinical studies in Spain, its psychometric properties (its reliability, validity and sensitivity to change) must be verified in a subsequent validation study.}, }
@article {pmid12677143, year = {2003}, author = {Zmora, O and Potenti, FM and Wexner, SD and Pikarsky, AJ and Efron, JE and Nogueras, JJ and Pricolo, VE and Weiss, EG}, title = {Gracilis muscle transposition for iatrogenic rectourethral fistula.}, journal = {Annals of surgery}, volume = {237}, number = {4}, pages = {483-487}, pmid = {12677143}, issn = {0003-4932}, mesh = {Aged ; Humans ; Intraoperative Complications/*surgery ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Rectal Fistula/*surgery ; Retrospective Studies ; Thigh ; Urethral Diseases/*surgery ; Urinary Fistula/*surgery ; }, abstract = {OBJECTIVE: To assess the utility of gracilis muscle transposition in the treatment of iatrogenic rectourethral fistula.<br><br>SUMMARY BACKGROUND DATA: Iatrogenic rectourethral fistula poses a rare but challenging complication of treatment for prostate cancer. A variety of procedures have been described to treat this condition, none of which has gained acceptance as the procedure of choice. The aim of this study was to review the authors' experience with gracilis muscle transposition in the treatment of iatrogenic rectourethral fistula.<br><br>METHODS: A retrospective chart review of all patients who underwent gracilis muscle transposition for iatrogenic rectourethral fistula was performed, and follow-up was established by telephone interview. Successful repair was defined as absence of a fistula after reversal of fecal and urinary diversions.<br><br>RESULTS: Eleven men, mean age of 62 years, underwent 12 gracilis muscle transpositions for rectourethral fistula between 1996 and 2001. Six patients had a history of pelvic radiotherapy, and five patients had previous failed attempts to repair the fistula. In nine patients, the fistula healed following gracilis muscle transposition. One patient developed a rectocutaneous fistula that healed with fibrin glue injection, and one developed perineal sepsis requiring debridement of the transposed gracilis. This patient underwent a second gracilis transposition, which uneventfully healed. Overall, all of the patients had closure of their diverting stomas and maintained healed rectourethral fistulas. There were no intraoperative complications, and the only long-term complication of this procedure was mild medial thigh numbness in two patients.<br><br>CONCLUSIONS: Gracilis muscle transposition is an effective surgical treatment for iatrogenic rectourethral fistula. It is associated with low morbidity and a high success rate.}, }
@article {pmid12658825, year = {2002}, author = {Sielezneff, I and Pirro, N and Ouaissi, M and Cesari, J and Consentino, B and Sastre, B}, title = {[Surgical treatment of anal incontinence].}, journal = {Annales de chirurgie}, volume = {127}, number = {9}, pages = {670-679}, doi = {10.1016/s0003-3944(02)00881-7}, pmid = {12658825}, issn = {0003-3944}, mesh = {Adult ; Age Factors ; Aged ; Anal Canal/innervation/*surgery ; Child ; Cohort Studies ; Electric Stimulation Therapy ; Fecal Incontinence/epidemiology/etiology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Muscle, Skeletal/transplantation ; Postoperative Complications ; Prostheses and Implants ; Quality of Life ; Suture Techniques ; Time Factors ; }, abstract = {Surgery is mandatory for fecal incontinence when medical treatments and reeducation by biofeedback are ineffective. Sphincter disruption is the most frequent cause. Sphincter repair with or without overlapping is indicated in the large majority of cases. Short-term results are good but result is not ever maintained with time. In case of failure, or when the defect concerns more than 180 degrees, it is necessary to use a substitutive technique. Artificial anal sphincter is often first proposed because of its apparent technical simplicity and because it is cheaper than dynamic graciloplasty. Results are excellent. Failures are due to local infection or device disfunction. Dynamic graciloplastie may be proposed in patients with severe perineal lesions, or failure of the other methods. Its results are also excellent, except for the patients having disordered rectal perception. Sacral nerve stimulation is limited to patients with idiopathic or neurologic incontinence. Because definitive implantation is done only following positive preoperative stimulation test, short-term results are very good.}, }
@article {pmid12640307, year = {2003}, author = {Maes, BD and Dalle, I and Geboes, K and Oellerich, M and Armstrong, VW and Evenepoel, P and Geypens, B and Kuypers, D and Shipkova, M and Geboes, K and Vanrenterghem, YF}, title = {Erosive enterocolitis in mycophenolate mofetil-treated renal-transplant recipients with persistent afebrile diarrhea.}, journal = {Transplantation}, volume = {75}, number = {5}, pages = {665-672}, doi = {10.1097/01.TP.0000053753.43268.F0}, pmid = {12640307}, issn = {0041-1337}, mesh = {Adult ; Aged ; Campylobacter Infections ; Diarrhea/*chemically induced ; Enterocolitis/*chemically induced/microbiology/*pathology/therapy ; Female ; Gastric Emptying ; Humans ; Immunosuppressive Agents/*adverse effects ; Kidney Transplantation ; Malabsorption Syndromes/chemically induced ; Male ; Middle Aged ; Mycophenolic Acid/*adverse effects/analogs &amp; derivatives ; }, abstract = {BACKGROUND: Diarrhea is the most frequently reported adverse event in mycophenolate mofetil (MMF)-treated transplant patients. The aim of this study was to explore the gastrointestinal tract in MMF-treated renal transplant recipients with persistent afebrile diarrhea to characterize its nature and etiology.<br><br>METHODS: Renal transplant recipients with persistent afebrile diarrhea (daily fecal output >200 g) were prospectively investigated for infections, morphologic, and functional (gastrointestinal motility and intestinal absorptive capacity) integrity of the gastrointestinal tract; 26 patients met the inclusion criteria.<br><br>RESULTS: All but one patient had an erosive enterocolitis. Seventy percent of the patients had malabsorption of nutrients, contributing to the diarrhea. In +/-60%, an infectious origin was demonstrated and successfully treated with antimicrobial agents without changes in immunosuppressive regimen. In +/-40%, no infection occurred, but a Crohn's disease-like pattern of inflammation was noted. These patients also had a less pronounced bile-acid malabsorption but a significant faster colonic transit time, correlating with the trough level of mycophenolic acid (MPA). Cessation of MMF, however, was associated with allograft rejection in one third of these patients.<br><br>CONCLUSIONS: Persistent afebrile diarrhea in renal transplant recipients is characterized by erosive enterocolitis, which is of infectious origin in +/-60%. In +/-40%, a Crohn's disease-like (entero-)colitis was present. Because reduction or cessation of MMF was the only effective therapy, MPA or one of its metabolites may be suggested as a possible cause. However, reduction or cessation of MMF was associated with an increased risk for rejection.}, }
@article {pmid12625508, year = {2003}, author = {Besselsen, DG and Wagner, AM and Loganbill, JK}, title = {Detection of lymphocytic choriomeningitis virus by use of fluorogenic nuclease reverse transcriptase-polymerase chain reaction analysis.}, journal = {Comparative medicine}, volume = {53}, number = {1}, pages = {65-69}, pmid = {12625508}, issn = {1532-0820}, support = {R01 RR14072/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Cricetinae ; DNA Primers ; Female ; Fluorescent Dyes ; Lymphocytic choriomeningitis virus/genetics/*isolation &amp; purification ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Pregnancy ; RNA, Viral/analysis ; Reverse Transcriptase Polymerase Chain Reaction/*methods ; Sensitivity and Specificity ; }, abstract = {Lymphocytic choriomeningitis virus (LCMV) induces persistent infections in laboratory mice; is a known contaminant of biological materials, such as transplantable tumor cell lines; and is of great concern in animal facilities due to its zoonotic potential. Fluorogenic nuclease reverse transcriptase-polymerase chain reaction (fnRT-PCR) assays combine RT-PCR with an internal fluorogenic hybridization probe, thereby potentially enhancing specificity and eliminating post-PCR processing. An fnRT-PCR assay specific for LCMV was, therefore, developed by targeting primer and probe sequences to a unique region of the LCMV nucleocapsid (NP) gene. The LCMV fnRT-PCR assay detected only LCMV and did not detect other RNA viruses that naturally infect rodents. The fnRT-PCR assay detected as little as one picogram of LCMV RNA, but was 100-fold less sensitive when directly compared with the mouse antibody production test. The fnRT-PCR assay was also able to detect viral RNA in numerous tissues and in feces and cage swipe specimens collected from experimentally inoculated BALB/c mice, but did not detect any viral RNA in similar samples collected from age- and strain-matched mock-infected mice. In conclusion, the LCMV fnRT-PCR assay offers a potentially high-throughput diagnostic assay to detect LCMV in mice and contaminated biological materials.}, }
@article {pmid12621493, year = {2003}, author = {Ansorg, R and Rath, PM and Runde, V and Beelen, DW}, title = {Influence of intestinal decontamination using metronidazole on the detection of methanogenic Archaea in bone marrow transplant recipients.}, journal = {Bone marrow transplantation}, volume = {31}, number = {2}, pages = {117-119}, doi = {10.1038/sj.bmt.1703797}, pmid = {12621493}, issn = {0268-3369}, mesh = {Adult ; Anti-Bacterial Agents/*therapeutic use ; Archaea/drug effects/*isolation &amp; purification ; Bacteria, Anaerobic/drug effects/isolation &amp; purification ; Bone Marrow Transplantation/*physiology ; Decontamination/methods ; Euryarchaeota/drug effects/isolation &amp; purification ; Feces/*microbiology ; Female ; Humans ; Intestines/*microbiology ; Male ; Methane/*analysis ; Metronidazole/*therapeutic use ; Middle Aged ; }, abstract = {Methane-forming microbes of the phylogenetic domain Archaea are part of the strictly anaerobic microflora of the human intestine. In bone marrow transplant (BMT) recipients, the regimen of intestinal decontamination with metronidazole is targeted to anaerobic bacteria. The effect on the anaerobic methanoarchaea, however, is unknown. Therefore, the faeces of patients undergoing BMT were investigated for methane production. The anoxic Hungate technique and an archaeal growth medium were used to culture faecal specimens. Methane production was measured in the head space of the culture bottles by gas chromatography using a thermal conductivity detector. In a testing serial specimen of 100 patients, 13 patients were found to bear methanogens, and 11 of these patients received metronidazole. The methane-producing faecal specimens occurred before metronidazole use in three patients, during the first week in five patients, and after cessation in three patients. No specimen of the 11 patients that was obtained during the 2nd-5th week of gut decontamination showed methane production. It is concluded that use of metronidazole directed against faecal anaerobic bacteria also suppresses or eliminates faecal methanogenic Archaea.}, }
@article {pmid12576256, year = {2003}, author = {Singh, K and Cortes, E and Reid, WM}, title = {Evaluation of the fascial technique for surgical repair of isolated posterior vaginal wall prolapse.}, journal = {Obstetrics and gynecology}, volume = {101}, number = {2}, pages = {320-324}, doi = {10.1016/s0029-7844(02)02616-9}, pmid = {12576256}, issn = {0029-7844}, mesh = {Adult ; Fascia/*transplantation ; Female ; Follow-Up Studies ; Gynecologic Surgical Procedures/*methods ; Humans ; Longitudinal Studies ; Middle Aged ; Patient Satisfaction ; Postmenopause ; Premenopause ; Prospective Studies ; Plastic Surgery Procedures/methods ; Recovery of Function ; Severity of Illness Index ; Treatment Outcome ; Uterine Prolapse/diagnosis/*surgery ; Vagina/physiopathology/surgery ; }, abstract = {OBJECTIVE: To study the anatomic and functional efficacy and assess long-term success of the fascial technique in the repair of rectocele.<br><br>METHODS: Forty-two women with symptomatic posterior vaginal wall prolapse of at least stage II underwent a surgical repair using the technique of reconstruction of the rectovaginal septum. These women were evaluated at 6 weeks and 18 months postoperatively for anatomic improvement in the grade of their rectocele and a functional improvement in their vaginal, bowel, and sexual symptoms.<br><br>RESULTS: Ninety-five percent (40 of 42) were assessed at 6 weeks and 78.5% (33 of 42) attended follow-up at 18 months. Preoperative symptoms included 1) vaginal protrusion (78%); 2) defecation symptoms (76%), which included fecal incontinence alone in 9.5%, evacuation difficulties in 57%, and both fecal incontinence and evacuation difficulties in 9.5%; and 3) sexual dysfunction (33%). At 6-week follow-up there was resolution of vaginal protrusion in 87.5%, and bowel symptoms in 87%. At 18 months there was anatomic cure in 92%, improvement in defecation in 81%, and improvement of sexual dysfunction in 35%. No major complications were seen.<br><br>CONCLUSION: This technique is effective in providing relatively long anatomic cure of the rectocele and resolution of its symptoms.}, }
@article {pmid12574264, year = {2003}, author = {Turgeon, DK and Novicki, TJ and Quick, J and Carlson, L and Miller, P and Ulness, B and Cent, A and Ashley, R and Larson, A and Coyle, M and Limaye, AP and Cookson, BT and Fritsche, TR}, title = {Six rapid tests for direct detection of Clostridium difficile and its toxins in fecal samples compared with the fibroblast cytotoxicity assay.}, journal = {Journal of clinical microbiology}, volume = {41}, number = {2}, pages = {667-670}, pmid = {12574264}, issn = {0095-1137}, mesh = {Bacterial Toxins/*analysis ; Clostridioides difficile/genetics/*isolation &amp; purification ; Feces/chemistry/*microbiology ; Fibroblasts/*drug effects ; Humans ; Immunoassay ; }, abstract = {Clostridium difficile is one of the most frequent causes of nosocomial gastrointestinal disease. Risk factors include prior antibiotic therapy, bowel surgery, and the immunocompromised state. Direct fecal analysis for C. difficile toxin B by tissue culture cytotoxin B assay (CBA), while only 60 to 85% sensitive overall, is a common laboratory method. We have used 1,003 consecutive, nonduplicate fecal samples to compare six commercially available immunoassays (IA) for C. difficile detection with CBA: Prima System Clostridium difficile Tox A and VIDAS Clostridium difficile Tox A II, which detect C. difficile toxin A; Premier Cytoclone A/B and Techlab Clostridium difficile Tox A/B, which detect toxins A and B; and ImmunoCard Clostridium difficile and Triage Micro C. difficile panels, which detect toxin A and a species-specific antigen. For all tests, Triage antigen was most sensitive (89.1%; negative predictive value [NPV] = 98.7%) while ImmunoCard was most specific (99.7%; positive predictive value [PPV] = 95.0%). For toxin tests only, Prima System had the highest sensitivity (82.2%; NPV = 98.0%) while ImmunoCard had the highest specificity (99.7%; PPV = 95.0%). Hematopoietic stem cell transplant (HSCT) patients contributed 44.7% of all samples tested, and no significant differences in sensitivity or specificity were noted between HSCT and non-HSCT patients. IAs, while not as sensitive as direct fecal CBA, produce reasonable predictive values, especially when both antigen and toxin are detected. They also offer significant advantages over CBA in terms of turnaround time and ease of use.}, }
@article {pmid12552400, year = {2003}, author = {Koch, SM and Baeten, CG}, title = {[Sphincter replacement grafts].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {74}, number = {1}, pages = {15-19}, doi = {10.1007/s00104-002-0563-9}, pmid = {12552400}, issn = {0009-4722}, mesh = {Anal Canal/injuries/*surgery ; Electric Stimulation Therapy/instrumentation ; Fecal Incontinence/etiology/*surgery ; Follow-Up Studies ; Humans ; Muscle, Skeletal/innervation/transplantation ; Postoperative Complications/etiology/surgery ; Prostheses and Implants ; Prosthesis Implantation ; }, abstract = {An anal sphincter replacement graft can be carried out when sphincter lesions occur after unsuccessful conservative or other treatment. Today, two different techniques are used to take over the function of the sphincter. The dynamic gracilis graft can be carried out if a non-atrophied,well innervated m. gracilis is present. This technique is carried out on patients whose incontinence is the result of a trauma,pudendopathy or imperforate anus. It can be extended to the construction of a neo-anus after abdominal resection. The artificial anal sphincter is used whenever the previous method fails or can not be used due to a non-vital, denervated or the lack of the m. gracilis. Older methods such as non-stimulated gracilis, glureus or Thiersch grafts are not commonly used.}, }
@article {pmid12521120, year = {2002}, author = {Horta, JA and Staats, CC and Casali, AK and Ribeiro, AM and Schrank, IS and Schrank, A and Vainstein, MH}, title = {Epidemiological aspects of clinical and environmental Cryptococcus neoformans isolates in the Brazilian state Rio Grande do Sul.}, journal = {Medical mycology}, volume = {40}, number = {6}, pages = {565-571}, doi = {10.1080/mmy.40.6.565.571}, pmid = {12521120}, issn = {1369-3786}, mesh = {AIDS-Related Opportunistic Infections/*epidemiology/microbiology ; Animals ; Bird Diseases/*epidemiology/microbiology ; Brazil/epidemiology ; Cerebrospinal Fluid/microbiology ; Columbidae ; Cryptococcosis/*epidemiology/microbiology/veterinary ; Cryptococcus neoformans/*classification/*genetics/isolation &amp; purification ; DNA, Fungal/analysis ; Feces/microbiology ; *Genetic Variation ; Humans ; Meningitis, Cryptococcal/epidemiology/microbiology ; Polymerase Chain Reaction ; Random Amplified Polymorphic DNA Technique ; Serotyping ; }, abstract = {Cryptococcus neoformans is a pathogenic fungus that causes life-threatening meningoencephalitis in immunocompromised patients (HIV-positive patients), and lymphoproliferative disorders in patients subjected to organ transplantation and other immunosuppressive therapies. This fungus is commonly found in soil and avian excreta, mainly from pigeon and turkey. We describe the isolation and characterization of 17 clinical and 10 environmental (pigeon excreta) isolates from the Brazilian state Rio Grande do Sul. We analyzed capsule formation, carbon assimilation pattern, canavanine-glycine-bromothymol blue (CGB) reaction, and nitrate and urease tests, as well as susceptibility to antifungal drugs. The genetic variability among C. neoformans isolates was studied using randomly amplified polymorphic DNA (RAPD) analysis. Eight of 22 arbitrary polymerase chain reaction primers used confirmed genetic polymorphism among the environmental isolates tested, suggesting that it remains feasible to use RAPD analysis as a typing method. Three of the selected primers yielded 10 molecular subclasses. The majority of the clinical isolates were assigned to the molecular subclass F. The RAPD data obtained reinforce the developing consensus about the population structure of this fungus.}, }
@article {pmid12512044, year = {2003}, author = {Setchell, KD and Heubi, JE and Bove, KE and O'Connell, NC and Brewsaugh, T and Steinberg, SJ and Moser, A and Squires, RH}, title = {Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy.}, journal = {Gastroenterology}, volume = {124}, number = {1}, pages = {217-232}, doi = {10.1053/gast.2003.50017}, pmid = {12512044}, issn = {0016-5085}, support = {FD R-000995/FD/FDA HHS/United States ; M01 RR 08084/RR/NCRR NIH HHS/United States ; P01 DK 46405/DK/NIDDK NIH HHS/United States ; }, mesh = {Bile/chemistry ; Bile Acids and Salts/analysis/*biosynthesis/therapeutic use/urine ; Biomarkers/analysis ; Blood/metabolism ; Cholestanols/*metabolism ; DNA Mutational Analysis ; Female ; Gas Chromatography-Mass Spectrometry ; Humans ; Infant, Newborn ; Liver Diseases/*etiology/surgery ; Liver Transplantation ; Metabolism, Inborn Errors/*complications/drug therapy ; Mutation/physiology ; Peroxisomes/enzymology ; Racemases and Epimerases/genetics ; Spectrometry, Mass, Fast Atom Bombardment ; Urine/chemistry ; }, abstract = {BACKGROUND &amp; AIMS: Inborn errors of bile acid metabolism may present as neonatal cholestasis and fat-soluble vitamin malabsorption or as late onset chronic liver disease. Our aim was to fully characterize a defect in bile acid synthesis in a 2-week-old African-American girl presenting with coagulopathy, vitamin D and E deficiencies, and mild cholestasis and in her sibling, whose liver had been used for orthotopic liver transplantation (OLT).<br><br>METHODS: Bile acids were measured by mass spectrometry in urine, bile, serum, and feces of the patient and in urine from the unrelated recipient.<br><br>RESULTS: Liver biopsy specimens showed neonatal hepatitis with giant cell transformation and hepatocyte necrosis; peroxisomes were reduced in number. High concentrations of (25R)3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid in the urine, bile, and serum established a pattern similar to that of Zellweger syndrome and identical to the Alligator mississippiensis. Serum phytanic acid was normal, whereas pristanic acid was markedly elevated. Biochemical, MRI, and neurologic findings were inconsistent with a generalized defect of peroxisomal function and were unique. Analysis of the urine from the recipient of the deceased sibling's liver confirmed the same bile acid synthetic defect. A deficiency in 2-methylacyl-CoA racemase, which is essential for conversion of (25R)THCA to its 25S-isomer, the substrate to initiate peroxisomal beta-oxidation to primary bile acids, was confirmed by DNA analysis revealing a missense mutation (S52P) in the gene encoding this enzyme. Long-term treatment with cholic acid normalized liver enzymes and prevented progression of symptoms.<br><br>CONCLUSIONS: This genetic defect further highlights bile acid synthetic defects as a cause of neonatal cholestasis.}, }
@article {pmid12473471, year = {2002}, author = {Olver, WJ and James, SA and Lennard, A and Galloway, A and Roberts, IN and Boswell, TC and Russell, NH}, title = {Nosocomial transmission of Saccharomyces cerevisiae in bone marrow transplant patients.}, journal = {The Journal of hospital infection}, volume = {52}, number = {4}, pages = {268-272}, doi = {10.1053/jhin.2002.1314}, pmid = {12473471}, issn = {0195-6701}, mesh = {Adult ; Amphotericin B/therapeutic use ; Antifungal Agents/therapeutic use ; Bone Marrow Transplantation/*adverse effects ; Carrier State/*transmission ; Cross Infection/drug therapy/*etiology/*transmission ; DNA, Fungal/analysis ; Drug Therapy, Combination ; Fatal Outcome ; Feces/microbiology ; Female ; Flucytosine/therapeutic use ; Genotype ; Humans ; *Immunocompromised Host ; Infection Control ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy ; Male ; Mass Screening ; Multiple Organ Failure/microbiology ; Mycoses/drug therapy/*etiology/*transmission ; Pharynx/microbiology ; *Saccharomyces cerevisiae/genetics ; }, abstract = {Saccharomyces cerevisiae is an unusual cause of clinical infection. We describe three bone marrow transplant patients on a haematology unit who developed possible invasive disease with the organism. Two patients died and both these patients appeared to have a related strain of S. cerevisiae. Screening for S. cerevisiae from throat and stool samples revealed four further patients who were carriers. Genotyping of the invasive and carriage strains demonstrated an indistinguishable strain from patients who had been on the unit at the same time, suggesting cross-infection.}, }
@article {pmid12425879, year = {2002}, author = {Ayats-Ardite, J and Cisneros-Herreros, JM and Pérez-Sáenz, JL and de la Torre-Cisneros, J}, title = {[Infectious disease assessment in solid organ transplant candidates].}, journal = {Enfermedades infecciosas y microbiologia clinica}, volume = {20}, number = {9}, pages = {448-461}, doi = {10.1016/s0213-005x(02)72841-3}, pmid = {12425879}, issn = {0213-005X}, mesh = {Biomarkers ; Body Fluids/microbiology/virology ; Contraindications ; Drug Resistance, Multiple, Bacterial ; Feces/parasitology ; HIV Infections/diagnosis ; Hepatitis, Viral, Human/diagnosis ; Humans ; *Infection Control ; Infections/*diagnosis/diagnostic imaging/therapy ; Medical Records ; Patient Education as Topic ; Patient Selection ; Physical Examination ; Postoperative Complications/*prevention &amp; control ; *Preoperative Care ; Radiography ; Risk Factors ; *Transplantation ; Tuberculin Test ; Vaccination ; Virus Latency ; }, abstract = {BACKGROUND: Infections are one of the leading causes of morbidity and mortality in solid organ transplant recipients. Many of these infections can be prevented or their effects reduced by accurate preoperative evaluation of risk in the transplantation candidate. The elaboration of guidelines using a multidisciplinary approach can help to establish more rational diagnostic, therapeutic, and preventive measures in this setting.<br><br>OBJECTIVE: To elaborate guidelines for the assessment of infectious diseases in transplant candidates, based on consensus among professionals in this field and under the auspices of Spanish scientific societies.<br><br>MATERIAL AND METHODS: The Infections in Transplant Patients Group (GESITRA), within the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), appointed a panel of four microbiologists and infectious disease specialists to elaborate a draft of the guidelines, which was subsequently approved by all the members of this Group. With the support of the National Transplant Organization, the GESITRA document was then presented to various professionals in this field so they could provide their comments and suggestions.<br><br>RESULTS: The final document, after incorporation of all appropriate modifications and suggestions, is presented herein. The guidelines focus on the following: a) diagnosis of active and latent infections, and identification of risk factors in the candidate; b) recommended approach for infections diagnosed during the evaluation process and their corresponding treatment; c) definition of infections contraindicating transplantation; and d) prevention of post-transplantation infectious complications by systematic vaccination and instruction on preventive measures provided to patients, their relatives, and persons living with them.<br><br>DISCUSSION: Using a multidisciplinary approach that included the efforts of experts in the field and the collaboration of scientific societies, a comprehensive document containing specific recommendations was elaborated. Systematic review of the guidelines in the future is considered worthwhile by both the authors and supporters of this document.}, }
@article {pmid12392303, year = {2002}, author = {Shiga, S and Fujimoto, H and Mori, Y and Sakata, T and Hamaguchi, Y and Wang, FS and Inomata, Y and Tohyama, K and Ichiyama, S}, title = {Immature granulocyte count after liver transplantation.}, journal = {Clinical chemistry and laboratory medicine}, volume = {40}, number = {8}, pages = {775-780}, doi = {10.1515/CCLM.2002.133}, pmid = {12392303}, issn = {1434-6621}, mesh = {Biomarkers/blood ; Flow Cytometry ; Graft Rejection/blood ; Granulocytes/*cytology/immunology ; Humans ; Immunophenotyping ; Infections/blood/etiology ; Inflammation/blood ; Leukocyte Count ; Liver Transplantation/*adverse effects ; Melena/blood/etiology ; Prognosis ; Time Factors ; }, abstract = {We evaluated the significance of immature granulocyte (IG) count during the clinical course after liver transplantation. We counted IG using the flow cytometric method with CD16, CD11b, and CD45 antibodies. Samples were obtained from 31 patients in the Department of Transplantation and Immunology, and we determined (i) the distribution of IG peak value, (ii) the distribution of IG peak time-points, (iii) the clinical background of patients with high IG, and (iv) the clinical course of high IG cases. We observed the appearance of IG (100/microl or higher) in the majority of the patients (23 out of 31 patients; 74.2%). The IG peak was detected on the 19th day after transplantation. We observed serious complications, such as melena, rejection, or severe infection, in high IG (500/microl or higher) cases. We observed instances of inflammation with low C-reactive protein (CRP) value in the presence of IG. We believe that IG is a useful marker to monitor inflammation.}, }
@article {pmid12378698, year = {2002}, author = {Mugnani, G and Bergami, M and Lazzarotto, T and Bedani, PL}, title = {[Intestinal infection by cytomegalovirus in kidney transplantation: diagnostic difficulty in the course of mycophenolate mofetil therapy].}, journal = {Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia}, volume = {19}, number = {4}, pages = {483-484}, pmid = {12378698}, issn = {0393-5590}, mesh = {Biomarkers ; Colitis/chemically induced/complications/diagnosis/*virology ; Cytomegalovirus/isolation &amp; purification ; Cytomegalovirus Infections/complications/*diagnosis ; Diagnosis, Differential ; Diarrhea/*etiology/virology ; Feces/virology ; Fever/etiology ; Graft vs Host Disease/prevention &amp; control ; Humans ; Immunosuppressive Agents/*adverse effects ; *Kidney Transplantation ; Male ; Middle Aged ; Mycophenolic Acid/*adverse effects/analogs &amp; derivatives ; Phosphoproteins/blood ; Postoperative Complications/*diagnosis/virology ; Viral Matrix Proteins/blood ; Virus Cultivation ; }, }
@article {pmid12352382, year = {2002}, author = {Yerkes, EB and Rink, RC and Cain, MP and Casale, AJ}, title = {Use of a Monti channel for administration of antegrade continence enemas.}, journal = {The Journal of urology}, volume = {168}, number = {4 Pt 2}, pages = {1883-5; discussion 1885}, doi = {10.1097/01.ju.0000028005.04404.a1}, pmid = {12352382}, issn = {0022-5347}, mesh = {Adolescent ; Adult ; Catheterization ; Child ; Colostomy/*methods ; Enema/*methods ; Fecal Incontinence/*congenital/therapy ; Female ; Follow-Up Studies ; Humans ; Ileum/transplantation ; Male ; Outcome and Process Assessment, Health Care ; }, abstract = {PURPOSE: Success with Malone antegrade continence enemas (MACE) requires reliable access to the colon and a customized enema regimen. Use of the appendix in situ provides a natural and well-vascularized conduit. When the appendix is absent or inadequate, alternative techniques are required. We report our experience using Monti channels to administer antegrade continence enemas.<br><br>MATERIALS AND METHODS: Of the 106 MACE procedures performed in 53 months a Monti-MACE was created in 13. Indications for use of ileum, technique, ease of catheterization and incidence of complications were reviewed.<br><br>RESULTS: Mean followup was 21.7 months. Two patients had transient difficulty advancing the catheter into the cecum. Stoma revisions were required for critical stenosis in 2 patients (15.4%). Stoma leakage occurred in 1 patient after multiple stoma revisions.<br><br>CONCLUSIONS: The Monti-MACE provides continent access to the colon for antegrade enemas. The rate of stomal revision is only slightly higher than that reported for appendicocecostomy. While use of the appendix in situ remains our preference, reconfigured ileum is a reliable substitute in patients without a suitable appendix.}, }
@article {pmid12149765, year = {2002}, author = {Egawa, H and Yorifuji, T and Sumazaki, R and Kimura, A and Hasegawa, M and Tanaka, K}, title = {Intractable diarrhea after liver transplantation for Byler's disease: successful treatment with bile adsorptive resin.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {8}, number = {8}, pages = {714-716}, doi = {10.1053/jlts.2002.34384}, pmid = {12149765}, issn = {1527-6465}, mesh = {Adolescent ; Bile/*metabolism ; Bile Acids and Salts/*metabolism ; Body Height ; Child ; Child, Preschool ; Cholestasis, Intrahepatic/*surgery ; Composite Resins/*therapeutic use ; Diarrhea/*etiology/therapy ; Feces/chemistry ; Female ; Growth ; Humans ; *Liver Transplantation ; Male ; *Postoperative Complications ; Retrospective Studies ; }, abstract = {Intractable diarrhea and prolonged growth retardation after liver transplantation for Byler's disease are serious complications limiting the ultimate outcome of liver transplantation for this disease. However, details of these complications have not been documented thoroughly. Six patients with Byler's disease developed intractable diarrhea after living donor liver transplantation. Because of high bile acid concentrations in stool, four patients were treated with bile acid adsorptive resin for bile acid diarrhea, and all showed improved bowel movements. Four of these patients who were followed up for 1 year registered a significant height gain. Also, the cause of postoperative diarrhea and growth retardation in patients with Byler's disease after liver transplantation is discussed.}, }
@article {pmid12142812, year = {2002}, author = {Rodriguez-Baez, N and O'Brien, R and Qiu, SQ and Bass, DM}, title = {Astrovirus, adenovirus, and rotavirus in hospitalized children: prevalence and association with gastroenteritis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {35}, number = {1}, pages = {64-68}, doi = {10.1097/00005176-200207000-00014}, pmid = {12142812}, issn = {0277-2116}, support = {DK52389/DK/NIDDK NIH HHS/United States ; DK7762/DK/NIDDK NIH HHS/United States ; }, mesh = {Adenoviridae/*isolation &amp; purification ; Adenoviridae Infections/diagnosis/epidemiology ; Astroviridae Infections/diagnosis/epidemiology ; *Child, Hospitalized ; Child, Preschool ; Feces/virology ; Gastroenteritis/*virology ; Humans ; Immunocompromised Host ; Infant ; Mamastrovirus/*isolation &amp; purification ; Organ Transplantation ; Rotavirus/*isolation &amp; purification ; Rotavirus Infections/diagnosis/epidemiology ; Seasons ; }, abstract = {BACKGROUND: Agents of viral gastroenteritis such as astrovirus, rotavirus, and adenovirus are common pediatric pathogens accounting for many physician visits, hospital admissions, and nosocomial infections. Previous hospital-based prevalence studies have examined mainly symptomatic children.<br><br>PURPOSE: To evaluate the prevalence of astrovirus, rotavirus, and adenovirus infections among hospitalized children less than 6 years of age, regardless of symptoms, and determine association with gastroenteritis.<br><br>METHODS: From September 1998 to June 2000, stool specimens were collected twice weekly from children less than five years of age admitted to two wards in a tertiary-care children's hospital. A total of 480 samples were obtained from 309 hospitalizations. Stools were examined using antibody-based ELISA for astrovirus, rotavirus, and adenovirus. Clinical data was abstracted from patient records.<br><br>RESULTS: Twenty one percent of the children had gastroenteritis symptoms at some point during their hospitalizations (43% were hospital acquired). Astrovirus was detected in 5.2% of all children compared to 6.8% with rotavirus and 0.8% with adenovirus serotypes 40 or 41. Nosocomial acquisition was common. Seventy five percent of astrovirus infections and 90% rotavirus infections were symptomatic. Astrovirus infections were significantly more likely to occur in younger infants and in children with compromised immunity. Rotavirus infections were significantly more likely to cause dehydration. In a three-year passive surveillance of gastroenteritis at the hospital, astrovirus and rotavirus infections peaked simultaneously in winter months.<br><br>CONCLUSIONS: Rotavirus and astrovirus are common symptomatic infections on pediatric wards and contribute greatly to inpatient morbidity. Adenoviruses played a limited role in gastroenteritis in hospitalized children in this study.}, }
@article {pmid12131685, year = {2002}, author = {Hellinger, WC and Yao, JD and Alvarez, S and Blair, JE and Cawley, JJ and Paya, CV and O'Brien, PC and Spivey, JR and Dickson, RC and Harnois, DM and Douglas, DD and Hughes, CB and Nguyen, JH and Mulligan, DC and Steers, JL}, title = {A randomized, prospective, double-blinded evaluation of selective bowel decontamination in liver transplantation.}, journal = {Transplantation}, volume = {73}, number = {12}, pages = {1904-1909}, doi = {10.1097/00007890-200206270-00009}, pmid = {12131685}, issn = {0041-1337}, mesh = {Colistin/*therapeutic use ; Double-Blind Method ; Drug Therapy, Combination/*therapeutic use ; Female ; Gentamicins/*therapeutic use ; Gram-Negative Aerobic Bacteria/drug effects/*isolation &amp; purification ; Humans ; Intestines/*microbiology ; Liver Transplantation/*methods ; Male ; Middle Aged ; Nystatin/*therapeutic use ; Prospective Studies ; Yeasts/drug effects/*isolation &amp; purification ; }, abstract = {BACKGROUND: Bacterial infection is a frequent, morbid, and mortal complication of liver transplantation. Selective bowel decontamination (SBD) has been reported to reduce the rate of bacterial infection after liver transplantation in uncontrolled trials, but benefits of this intervention have been less clear in controlled studies.<br><br>METHODS: Eighty candidates for liver transplantation were randomly assigned in a double-blinded fashion to an SBD regimen consisting of gentamicin 80 mg+polymyxin E 100 mg+nystatin 2 million units (37 patients) or to nystatin alone (43 patients). Both treatments were administered orally in 10 ml (increasing to 20 ml, according to predefined criteria), four times daily, through day 21 after transplantation. Anal fecal swab cultures were performed on days 0, 4, 7, and 21. Rates of infection, death, and charges for medical care were assessed from day 0 through day 60.<br><br>RESULTS: More than 85% of patients in both treatment groups began study treatment more than 3 days before transplantation. Rates of infection (32.4 vs. 27.9%), death (5.4 vs. 4.7%), or charges for medical care (median $194,000 vs. $163,000) were not reduced in patients assigned to SBD. On days 0, 4, 7, and 21, growth of aerobic gram-negative flora in fecal cultures of patients assigned to SBD was significantly less than that of patients taking nystatin alone; growth of aerobic gram-positive flora, anaerobes, and yeast was not significantly different.<br><br>CONCLUSION: Routine use of SBD in patients undergoing liver transplantation is not associated with significant benefit.}, }
@article {pmid12114937, year = {2002}, author = {Grogan, TA and Kramer, DJ}, title = {The rectal trumpet: use of a nasopharyngeal airway to contain fecal incontinence in critically ill patients.}, journal = {Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society}, volume = {29}, number = {4}, pages = {193-201}, doi = {10.1067/mjw.2002.125456}, pmid = {12114937}, issn = {1071-5754}, mesh = {Adult ; Aged ; Catheterization/*instrumentation ; Critical Illness ; Fecal Incontinence/nursing/*therapy ; Female ; Humans ; Intensive Care Units ; Intubation, Gastrointestinal/*instrumentation ; Male ; Middle Aged ; Risk Assessment ; Sampling Studies ; Sensitivity and Specificity ; Treatment Outcome ; }, abstract = {OBJECTIVE: Our objective was to determine if a nasopharyngeal airway (rectal trumpet) could be used as a fecal containment device with less trauma than traditional devices, such as a fecal incontinence pouch or balloon rectal catheter.<br><br>DESIGN: A single-subject clinical series was used.<br><br>SETTING AND SUBJECTS: A nonrandom sample of critically ill adult and geriatric patients (n = 22) with ongoing fecal incontinence who were receiving care in an intensive care and intermediate care unit in a university teaching hospital was used.<br><br>INSTRUMENTS: Direct observation, medical record review, a questionnaire, and interviews were used.<br><br>METHODS: The bedside nurses identified patients as study candidates. Clinical findings were documented in the medical record. The nurses providing patient care completed questionnaires.<br><br>MAIN OUTCOME MEASURES: Main outcome measures were parameters related to efficacy, practicality, and complications of use of the rectal trumpet: stool containment, skin and anal sphincter integrity, patient comfort, and ease of insertion.<br><br>RESULTS: All 22 patients (100%) had containment or improved containment of stool. Observable healing or restoration of skin integrity occurred in 90% of the patients with acquired skin injury (n = 20). None of the patients suffered any change in tone or damage to the anal sphincter. Although 41% of the patients experienced discomfort with insertion of the rectal trumpet, 86% had no discomfort while it was maintained in position. Insertion of the rectal trumpet was rated as easy by 84% of the responding nurses (n = 63).<br><br>CONCLUSIONS: Use of a rectal trumpet was well tolerated by patients and practical for nurses. Incontinence was contained and no untoward effects were noted. Benefits to the patient included wound healing and improved comfort.}, }
@article {pmid12091641, year = {2002}, author = {, }, title = {European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.6.3. Cancer risk after renal transplantation. Solid organ cancers: prevention and treatment.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {17 Suppl 4}, number = {}, pages = {32, 34-6}, pmid = {12091641}, issn = {0931-0509}, mesh = {Female ; Humans ; Kidney Neoplasms/therapy ; Kidney Transplantation/*adverse effects ; Male ; Neoplasms/etiology/prevention &amp; control/*therapy ; Prostatic Neoplasms/therapy ; }, abstract = {J. All renal transplant recipients should have regular ultrasonography of their native kidneys (when applicable) for screening of renal cell carcinomas, which are observed at much higher incidence in both dialysed and transplant patients. K. Guidelines published for screening and prevention of solid organ cancers in the general population should be strictly applied to transplant recipients, who are in general at higher cancer risk, but would benefit equally or even greater. L. All male renal transplant recipients aged 50 and over should have a yearly prostate specific antigen (PSA) test prior to a regular digital rectal examination. M. All female renal transplant recipients should have a yearly cervical (PAP) smear together with regular pelvic examination and regular mammography, according to national recommendations where available. N. All renal transplant recipients should undergo a faecal occult-blood testing as a screening for colorectal cancer and other (pre-malignant) lesions, according to national recommendations where available. O. In all these conditions, it is recommended to reduce immunosuppression whenever possible.}, }
@article {pmid12085426, year = {2002}, author = {Alarcón, MC and Fernández Lucas, M and Teruel, JL and Ortuño, J}, title = {[Hormone therapy with estrogen patches for the treatment of recurrent digestive hemorrhages in uremic patients].}, journal = {Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia}, volume = {22}, number = {2}, pages = {208-209}, pmid = {12085426}, issn = {0211-6995}, mesh = {Administration, Cutaneous ; Aged ; Angiodysplasia/complications/*drug therapy ; Erythropoietin/therapeutic use ; Estradiol/administration &amp; dosage/*therapeutic use ; Estrogen Replacement Therapy ; Female ; Gastrointestinal Hemorrhage/*drug therapy/etiology ; Hepatitis C, Chronic/complications ; Humans ; Kidney Transplantation ; Melena/drug therapy/etiology ; Recombinant Proteins ; Recurrence ; Renal Dialysis ; Uremia/*complications/therapy ; }, }
@article {pmid12077471, year = {2002}, author = {Zareba, G and Gelein, R and Morrow, PE and Utell, MJ}, title = {Percutaneous absorption studies of octamethylcyclotetrasiloxane using the human skin/nude mouse model.}, journal = {Skin pharmacology and applied skin physiology}, volume = {15}, number = {3}, pages = {184-194}, doi = {10.1159/000063547}, pmid = {12077471}, issn = {1422-2868}, mesh = {Administration, Cutaneous ; Animals ; Estrogens, Non-Steroidal/chemistry/*pharmacokinetics ; Female ; Fetus ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Siloxanes/chemistry/*pharmacokinetics ; Skin Absorption/*drug effects ; Skin Transplantation/methods ; Tissue Distribution/drug effects ; Transplantation, Heterologous/methods ; }, abstract = {Octamethylcyclotetrasiloxane (D(4)) has been used for more than 40 years in industrial applications and consumer products, including the personal care industry. D(4) possesses many properties suitable for personal care products, such as low surface tension, water repellency, and thermal and chemical stability. The skin is a major route of exposure to D(4)for humans. The main objective of this study was to evaluate the percutaneous absorption of neat D(4) in human skin using the human skin/nude mouse model. This information is needed to aid in assessing potential risks associated with the intended use of D(4). To determine whether D(4) accumulates in adipose tissue of the skin, the distribution of D(4) in human skin layers following application of neat D(4) was also evaluated. In this study, a mean of 1.09 +/- 0.46% of the applied dose was absorbed by the animal under semioccluded conditions. Only about 0.02% of the applied dose remained in the skin after 24 h of exposure (or 72 h after application). The majority (94.59 +/- 12.28%) of the dose evaporated from the site. Excretion in the volatile trap (or expired volatiles) accounted for 42% of the radioactivity that was absorbed, while 49% were excreted in the urine and feces. Despite the lipophilic properties of D(4), a significant accumulation of D(4) in adipose tissue of the skin was not observed 24 h following application to the surface of the skin. The small amount of D(4) detected in the skin was distributed mainly in the epidermis (61%), with lower amounts in the dermis (29%) and subcutaneous adipose tissue (10%). Dermal absorption studies using human skin transplanted onto nude mice showed that this model could be successfully applied for in vivo percutaneous absorption studies of D(4), and presumably of other cyclic siloxanes. The fraction of the percutaneous dose of D(4) absorbed in this model was found to be consistent with results reported by others using different experimental approaches.}, }
@article {pmid12075057, year = {2002}, author = {Molina, JM and Tourneur, M and Sarfati, C and Chevret, S and de Gouvello, A and Gobert, JG and Balkan, S and Derouin, F and , }, title = {Fumagillin treatment of intestinal microsporidiosis.}, journal = {The New England journal of medicine}, volume = {346}, number = {25}, pages = {1963-1969}, doi = {10.1056/NEJMoa012924}, pmid = {12075057}, issn = {1533-4406}, mesh = {Adult ; Antiprotozoal Agents/adverse effects/*therapeutic use ; Chronic Disease ; Cyclohexanes ; Double-Blind Method ; *Enterocytozoon/isolation &amp; purification ; Fatty Acids, Unsaturated/adverse effects/*therapeutic use ; Feces/parasitology ; Humans ; Immunocompromised Host ; Intestinal Diseases, Parasitic/diagnosis/*drug therapy ; Male ; Microsporidiosis/diagnosis/*drug therapy ; Opportunistic Infections/*drug therapy ; Sesquiterpenes ; }, abstract = {BACKGROUND: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a cause of chronic diarrhea, malabsorption, and wasting in immunocompromised patients. Currently, there is no effective treatment.<br><br>METHODS: We conducted a randomized, double-blind, placebo-controlled trial of fumagillin (60 mg per day orally for two weeks) in patients with chronic E. bieneusi infection. Efficacy was assessed primarily by the clearance of microsporidia, as evidenced by analysis of stool specimens. Patients in whom microsporidia were not cleared received treatment for two weeks with open-label fumagillin. After clearance of the parasite, follow-up stool examinations were performed monthly to detect relapses.<br><br>RESULTS: Twelve patients were enrolled in this study, 10 with the acquired immunodeficiency syndrome and 2 who had received organ transplants. Clearance of microsporidia occurred in all six of the patients in the fumagillin group, as compared with none of the six in the placebo group (P=0.002). Treatment with fumagillin was also associated with increases in absorption of D-xylose (P=0.003) and in Karnofsky performance scores (P<0.001) and with decreases in loperamide use (P=0.01) and total stool weight (P=0.04). There were serious adverse events (neutropenia and thrombocytopenia) in three patients in the fumagillin group; one patient in the placebo group had severe diarrhea. All six controls subsequently had clearance of microsporidia after open-label treatment with fumagillin. Relapses of the infection were identified in two patients during follow-up (median follow-up, 10 months).<br><br>CONCLUSIONS: Fumagillin is an effective treatment for chronic E. bieneusi infection in immunocompromised patients.}, }
@article {pmid12072635, year = {2002}, author = {Wexner, SD and Baeten, C and Bailey, R and Bakka, A and Belin, B and Belliveau, P and Berg, E and Buie, WD and Burnstein, M and Christiansen, J and Coller, J and Galandiuk, S and Lange, J and Madoff, R and Matzel, KE and Påhlman, L and Parc, R and Reilly, J and Seccia, M and Thorson, AG and Vernava, AM}, title = {Long-term efficacy of dynamic graciloplasty for fecal incontinence.}, journal = {Diseases of the colon and rectum}, volume = {45}, number = {6}, pages = {809-818}, doi = {10.1007/s10350-004-6302-1}, pmid = {12072635}, issn = {0012-3706}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/surgery ; Data Collection ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Mental Health ; Middle Aged ; Muscle, Smooth/*transplantation ; Quality of Life ; Retrospective Studies ; Surgical Stomas ; Treatment Outcome ; }, abstract = {PURPOSE: Patients with end-stage fecal incontinence in whom all standard medical and surgical treatment has failed or is not expected to be effective can be treated by dynamic graciloplasty. The aim of this study was to review the long-term efficacy data.<br><br>METHODS: Success was defined as a greater than 50 percent decrease in the frequency of incontinent episodes. Measured physiologic parameters included enema retention time and the difference in resting and squeezing pressures with and without stimulation. Measured quality-of-life parameters included the Medical Outcomes Study Short Form 36 Health Status Questionnaire, a Fecal Incontinence TyPE Specification, the Zung Self-Rating Depression Scale, the "state" portion of the State-Trait Anxiety Inventory, and the Visual Analog Scale, which were administered at baseline and through follow-up. Independent monitors collected data as part of a multicenter trial for patients who underwent dynamic graciloplasty from May 1993 to November 1999.<br><br>RESULTS: There were 129 patients entered in the study, 115 of whom met eligibility criteria and were included in the efficacy outcome analysis. Twenty-seven patients entered the study with a preexisting functioning stoma; the remaining 88 patients did not have a functioning stoma at the time of enrollment. Success was achieved in 62 percent of nonstoma patients at 12 months; these results were sustained at 18-month and 24-month follow-up assessments (55 and 56 percent, respectively). The success rate in the stoma patients increased from 37.5 percent (9 of 24 patients) at 12 months to 62 percent (13 of 21 patients) at 18 months and was 43 percent at 24 months (9 of 21 patients), which reflects the increased number of patients whose stomas were closed. Although the measured physiologic continence parameters generally improved, these changes did not correlate with continence outcome. The group of patients (stoma and nonstoma) who underwent dynamic graciloplasty showed statistically significant improvements in quality of life as measured by Medical Outcomes Study Short Form 36 physical function (P = 0.006) and social functioning (P = 0.02) assessment.<br><br>CONCLUSIONS: Dynamic graciloplasty was successful in the majority of patients with end-stage fecal incontinence. This result was usually achieved by 12 months after surgery in patients who did not have stomas and by 18 months in patients who had stomas at the time of dynamic graciloplasty surgery. These various improvements conferred by dynamic graciloplasty persisted during the two-year follow-up.}, }
@article {pmid12063482, year = {2002}, author = {Poh-Fitzpatrick, MB and Wang, X and Anderson, KE and Bloomer, JR and Bolwell, B and Lichtin, AE}, title = {Erythropoietic protoporphyria: altered phenotype after bone marrow transplantation for myelogenous leukemia in a patient heteroallelic for ferrochelatase gene mutations.}, journal = {Journal of the American Academy of Dermatology}, volume = {46}, number = {6}, pages = {861-866}, doi = {10.1067/mjd.2002.120460}, pmid = {12063482}, issn = {0190-9622}, support = {FD-R-001459/FD/FDA HHS/United States ; M01RR00073/RR/NCRR NIH HHS/United States ; P01AR44535/AR/NIAMS NIH HHS/United States ; R01AR18549/AR/NIAMS NIH HHS/United States ; R01DK26446/DK/NIDDK NIH HHS/United States ; }, mesh = {*Bone Marrow Transplantation ; DNA Primers ; Female ; Ferrochelatase/*genetics ; Humans ; Leukemia, Myelomonocytic, Acute/complications/*therapy ; Middle Aged ; Mutation ; Pedigree ; Phenotype ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Porphyria, Hepatoerythropoietic/complications/*diagnosis/genetics/pathology/*therapy ; Porphyrins/blood/metabolism/urine ; Protoporphyrins/blood/metabolism/urine ; }, abstract = {Acute myelogenous leukemia occurred in a 47-year-old woman whose 25-year history of cutaneous photosensitivity had been undiagnosed until abnormally high erythrocyte, plasma, and fecal protoporphyrin levels were discovered during evaluation for her hematologic disorder. She was found to be heteroallelic for ferrochelatase gene mutations, bearing a novel missense mutation caused by a C185-->G (Pro62-->Arg) transversion in exon 2 of one allele, and a previously described g-->a transition at the +5 position of the exon 1 donor site of the other allele, confirming a diagnosis of erythropoietic protoporphyria. Successful bone marrow transplantation from her brother, who is a mildly affected bearer of the second mutation, resulted in remission of the leukemia and in conversion of the protoporphyria phenotype of the recipient to one resembling that of the donor.}, }
@article {pmid12041019, year = {2001}, author = {Herman, RM and Wałega, P and Richter, P and Gryglewski, A and Popiela, T}, title = {[Preliminary results of dynamic gracilloplasty in the treatment of fecal incontinence].}, journal = {Przeglad lekarski}, volume = {58}, number = {12}, pages = {1047-1051}, pmid = {12041019}, issn = {0033-2240}, mesh = {Adult ; Anal Canal/physiopathology/*surgery ; *Electric Stimulation Therapy ; Fecal Incontinence/physiopathology/*surgery/therapy ; Female ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Prospective Studies ; Surgical Procedures, Operative/methods ; Treatment Outcome ; }, abstract = {UNLABELLED: Transposition of the gracilis muscle and its continuous electrical stimulation became a widely accepted method for treatment of patients with severe fecal incontinence. This method introduced to clinical practice by Baeten, Williams and Cavina has also been applied in total anorectal reconstruction following abdominoperineal rectum resection due to rectal cancer. This paper describes our (limited so far) experience with dynamic gracilloplasty procedure in the treatment of fecal incontinence in six patients with injury of anal sphincters. Complete preoperative work up was based on the clinical symptoms of fecal incontinence evaluated in detail according to Jorge and Wexner Incontinence Scoring System and the clinicomanometric continence criteria according to Holscheider scale. Anorectal manometry, transanal endosono-graphy, defecography and barostat study were performed in each patient before and following surgery. Dynamic gracilloplasty procedure was performed according to the modified Baeten procedure--as a one stage procedure. Medtronic equipment (IPG Pulse Generator 3023) was applied for gracilis stimulation. Short term program of fast-to-slow muscle conversion was applied starting from the second week following surgery. Patients were prospectively evaluated after surgery in terms of clinical symptoms and anorectal physiology. Complete fecal continence was achieved in all patients during the first month following surgery. There were no serious postoperative complications. It was shown during anorectal manometry that dynamic gracilloplsty could increase the anal sphincter pressure up to the range of healthy subjects, thus to prevent fecal leakage. The overall clinical and manometic results confirm the feasibility of anal dynamic gracilloplasty to restore fecal continence in patients with complete lost of sphincter function due to its traumatic injury or atresia. This technique deserves wider application also in Poland, since our initial results are encouraging.<br><br>CONCLUSION: According to our limited experience dynamic gracilloplasty proved safe and effective procedure for the treatment end-stage fecal incontinence. Complete preoperative diagnostic work-up is essential for proper patients selection and surgical procedure should be performed in a specialised surgical center.}, }
@article {pmid12032205, year = {2002}, author = {Koroshi, A and Babameto, A}, title = {Acute renal failure during acute fatty liver of pregnancy.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {17}, number = {6}, pages = {1110-1112}, doi = {10.1093/ndt/17.6.1110}, pmid = {12032205}, issn = {0931-0509}, mesh = {Acute Kidney Injury/*etiology ; Adult ; Fatal Outcome ; Fatty Liver/*complications ; Female ; Humans ; Jaundice/etiology ; Melena ; Pregnancy ; Pregnancy Complications/*physiopathology ; }, }
@article {pmid12024668, year = {2001}, author = {Kostov, D and Temelkov, T and Ivanov, K and Kiriazov, E and Ignatov, V and Kobakov, G}, title = {[Pseudocontinent colostomy - a manometric study].}, journal = {Khirurgiia}, volume = {57}, number = {3-4}, pages = {25-28}, pmid = {12024668}, issn = {0450-2167}, mesh = {Adult ; Aged ; Anal Canal/*surgery ; Bulgaria ; Colostomy/*methods/rehabilitation ; Defecation ; Fecal Incontinence/*prevention &amp; control ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry/instrumentation/*methods ; Middle Aged ; Muscle, Smooth/physiology/transplantation ; Postoperative Period ; Pressure ; Rectum/physiology/surgery ; Time Factors ; }, abstract = {The intraluminal pressure in terminal segment of colon has been studied at 42 patients undergone an exterpation of rectum and taken out pseudocontinent colostomy onto a front part of the abdomen. Schmidt's pattern smooth muscle muff, modified in the Clinic Surgery and Coloproctology at MU--Varna, has been transplanted around the colon, taken out as continent colostomy. The intraluminal pressure in the terminal segment of colon has been identified with an index of resistance on the side the smooth muscle muff against the spontaneous evacuation of the colon content. The pressure has been registrated at rest and after the mechanical dillatation of muscle muff. The pressure at the check group of 20 patients with taken out continent colostomy has been investigated manometrically. The basal intraluminal pressure at the patients with a transplanted smooth muscle muff has been 30 +/- 2.9 mmHg at the end of the first postoperative month, as it has been sustained permanent (29.7 +/- 3.0 mmHg) up to the second postoperative jear (0.001). The pressure has been increased up to the mean value of 42 +/- 2.5 mmHg, as it has been sustained at this level for a period of 120 sec. The basal intraluminal pressure at the patients with transplanted smooth muscle muff has been more then four times higher in comparison with the pressure in c. sigmoideum, which has been a prerequisite for stopping of the spontaneous evacuation. A conclusion has been done that the index of resistance in the terminal segment of colon has been depended on a functional potential of the smooth muscle muff directly. The transplanted muff has been an anatomic structure manifested a functional activity in terms of isolation.}, }
@article {pmid12004227, year = {2002}, author = {Kaiser, AM and Corman, ML}, title = {Modified perianal incisions in graciloplasty for fecal incontinence.}, journal = {Diseases of the colon and rectum}, volume = {45}, number = {5}, pages = {703-704}, doi = {10.1007/s10350-004-6274-1}, pmid = {12004227}, issn = {0012-3706}, mesh = {Fecal Incontinence/*surgery ; Humans ; Muscle, Skeletal/*transplantation ; Postoperative Complications ; }, }
@article {pmid11987097, year = {2002}, author = {Otaibi, AA and Barker, C and Anderson, R and Sigalet, DL}, title = {Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant.}, journal = {Journal of pediatric surgery}, volume = {37}, number = {5}, pages = {770-772}, doi = {10.1053/jpsu.2002.32274}, pmid = {11987097}, issn = {1531-5037}, mesh = {Abdominal Pain/diagnosis/etiology ; Bone Marrow Transplantation/*adverse effects ; Child ; Clostridioides difficile/isolation &amp; purification ; Diagnosis, Differential ; Enterocolitis/*diagnosis/*etiology ; Feces/microbiology ; Female ; Humans ; Leukocyte Count ; Male ; Neutropenia/diagnosis/*etiology ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND/PURPOSE: Neutropenic enterocolitis (typhlitis) is a common consideration after bone marrow transplantation. This study reviews the authors' experience with abdominal pain and typhlitis in an active pediatric bone marrow transplant program.<br><br>METHODS: The Pediatric Bone Marrow Transplant Program Database was reviewed for patients presenting with abdominal pain or typhlitis.<br><br>RESULTS: From 1993 to 2000 a total of 142 transplants have been performed. Of these, 97 patients had abdominal pain, and 5 had radiologically proven typhlitis. Nonspecific abdominal pain developed on the 12 +/- 11th day posttransplant, whereas patients in whom typhlitis developed were diagnosed on day 15.5 +/- 7. All patients were treated with prophylactic antibiotics consisting of acyclovir, fluconazole, and septra. With the onset of abdominal pain, 73 of 97 patients were placed on therapeutic antibiotics; patients identified with typhlitis had amphotericin plus GCSF added. No clinical features differentiated abdominal pain patients from typhlitis. Oral feeding and time of discharge was similar in both groups. Surgical intervention was not required, and no patients died with typhlitis.<br><br>CONCLUSIONS: Abdominal pain is a common symptom after bone marrow transplant; however, typhlitis is relatively rare, and surgical intervention was not required in this series. Broad-spectrum (including fungal) antibiotic therapy appears to be an effective treatment for typhlitis in this patient population.}, }
@article {pmid11985803, year = {2002}, author = {González Argenté, FX}, title = {[Anal neosphincters in the treatment of fecal incontinence].}, journal = {Gastroenterologia y hepatologia}, volume = {25}, number = {5}, pages = {316-318}, doi = {10.1016/s0210-5705(02)79027-4}, pmid = {11985803}, issn = {0210-5705}, mesh = {*Anal Canal ; Fecal Incontinence/*surgery ; Humans ; Muscle, Skeletal/*transplantation ; *Prostheses and Implants ; }, }
@article {pmid11930322, year = {2002}, author = {Waar, K and Muscholl-Silberhorn, AB and Willems, RJ and Slooff, MJ and Harmsen, HJ and Degener, JE}, title = {Genogrouping and incidence of virulence factors of Enterococcus faecalis in liver transplant patients differ from blood culture and fecal isolates.}, journal = {The Journal of infectious diseases}, volume = {185}, number = {8}, pages = {1121-1127}, doi = {10.1086/339682}, pmid = {11930322}, issn = {0022-1899}, mesh = {Bacteremia/*microbiology ; Enterococcus faecalis/*classification/genetics/pathogenicity ; Feces/*microbiology ; Genotype ; Humans ; Incidence ; Liver Transplantation/*adverse effects ; Microbial Sensitivity Tests ; Virulence ; }, abstract = {Enterococcus faecalis is a leading cause of infections in liver transplant patients. This study reviewed the incidence of virulence factors such as hemolysin, gelatinase, aggregation substances (asa1 and asa373), or the enterococcal surface protein (Esp) in isolates from liver transplant patients. In total, 133 isolates from liver transplant patients were compared with 47 isolates from feces of healthy volunteers and 66 isolates from blood cultures. Amplified fragment length polymorphism (AFLP) analysis indicates that the isolates from different clinical subgroups can be divided into genogroups with an AFLP similarity of >80% and different virulence factors. Hemolysin and asa1 might be associated with infection, as they are more frequent in isolates from blood cultures and transplant patients. Esp might be associated with colonization and spread, because it is more frequent in isolates from feces of healthy volunteers and transplant patients. An epidemic esp gene-positive strain among liver transplant patients supports this hypothesis.}, }
@article {pmid11899045, year = {2002}, author = {Wachtel, MR and Whitehand, LC and Mandrell, RE}, title = {Prevalence of Escherichia coli associated with a cabbage crop inadvertently irrigated with partially treated sewage wastewater.}, journal = {Journal of food protection}, volume = {65}, number = {3}, pages = {471-475}, doi = {10.4315/0362-028x-65.3.471}, pmid = {11899045}, issn = {0362-028X}, mesh = {Bacterial Adhesion ; Brassica/*microbiology ; Escherichia coli/classification/*isolation &amp; purification ; Food Contamination ; Food Handling/methods ; Food Microbiology ; Plant Roots/microbiology ; Prevalence ; Serotyping ; Sewage/microbiology ; Water Microbiology ; }, abstract = {Preharvest contamination of field crops may have many sources, including feces, soil, and irrigation water. In March 2000, a sewage spill released unchlorinated tertiary-treated effluent into a creek used to irrigate commercial produce. A field of young cabbage transplants was irrigated with creek water as the contaminated water flowed past this land. Cabbage samples were taken from plots within this field, and Escherichia coli was isolated from the roots of these plants but not from the edible portion of the cabbage. No E. coli was isolated from water samples or from control samples taken from a nearby cabbage field watered with chlorinated municipal water. The cabbage field under study had not been fertilized with manure for at least 2 years prior to the contamination incident. Six different E. coli serotypes were identified, although none of them proved to be pathogenic. These serotypes were separated into five groups by a RiboPrinter; the resulting groups correlated well with the serotypes and the locations in the field from which these strains were isolated. We previously found that certain nonpathogenic E. coli strains displayed lower levels of adherence to lettuce seedling roots in a hydroponic adherence assay. The E. coli field strains displayed variable patterns of adherence to lettuce seedlings: strain MW421 showed significantly lower root and shoot adherence levels than did the other field strains, while strains MW423 and MW425 showed significantly higher root and shoot adherence levels. These data suggest that water quality is of paramount importance for the food safety of growing crops.}, }
@article {pmid11888463, year = {2002}, author = {Hetzer, FH and Demartines, N and Handschin, AE and Clavien, PA}, title = {Stapled vs excision hemorrhoidectomy: long-term results of a prospective randomized trial.}, journal = {Archives of surgery (Chicago, Ill. : 1960)}, volume = {137}, number = {3}, pages = {337-340}, doi = {10.1001/archsurg.137.3.337}, pmid = {11888463}, issn = {0004-0010}, mesh = {Adult ; Aged ; Digestive System Surgical Procedures/*methods ; Fecal Incontinence/etiology/prevention &amp; control ; Female ; Hemorrhoids/*surgery ; Humans ; Length of Stay ; Male ; Middle Aged ; Pain Measurement ; Pain, Postoperative/etiology/prevention &amp; control ; Prospective Studies ; Recurrence ; Severity of Illness Index ; Single-Blind Method ; *Surgical Stapling ; *Sutures ; Treatment Outcome ; }, abstract = {HYPOTHESIS: Stapled hemorrhoidectomy offers several advantages over excision hemorrhoidectomy, including reduced postoperative pain, a reduced hospital stay, and an earlier recovery time. Furthermore, stapled hemorrhoidectomy is associated with lower hemorrhoidal recurrence on long-term follow-up.<br><br>DESIGN: A randomized prospective trial. Patients were blinded to the operation technique used. Follow-up occurred at 1 and 3 weeks and 12 months postoperatively.<br><br>SETTING: A university hospital providing primary, secondary, and tertiary care.<br><br>PATIENTS: Forty patients with second- and third-degree hemorrhoid disease were randomized to undergo either stapled or excision hemorrhoidectomy. Two patients were excluded. All patients were subject to a follow-up examination.<br><br>INTERVENTIONS: Stapled hemorrhoidectomy (Longo technique) vs excision hemorrhoidectomy (Ferguson technique).<br><br>MAIN OUTCOME MEASURES: Operating time, postoperative pain (measured by the visual analog scale), hospital stay, histologic features, morbidity, defecation habit, continence, recovery time (return to work), and hemorrhoid recurrence at 1 year.<br><br>RESULTS: Stapled vs excision hemorrhoidectomy was associated with a significantly reduced operating time (30 vs 43.25 minutes; P<.001), reduced postoperative pain scores (visual analog score) on the first 4 postoperative days (day 1: 2.7 vs 6.3; day 2: 1.7 vs 6.3; day 3: 0.8 vs 5.4; and day 4: 0.5 vs 4.8, where 0 indicates no pain, and 10, maximum pain; P < or = .001), and an earlier return to work (6.7 vs 20.7 days;P =.001). There were no differences for stapled vs excision hemorrhoidectomy in length of hospital stay (2.4 vs 2.1 days), complications (3 [15%] of 20 patients vs 5 [25%] of 20 patients), and recurrence rate (1 [5%] of 20 patients vs 1 [5%] of 20 patients).<br><br>CONCLUSIONS: Stapled hemorrhoidectomy is associated with reduced postoperative pain, earlier recovery time and return to work, and a similar recurrence rate compared with the excision technique. Provided further clinical trials confirm these findings, stapled hemorrhoidectomy may become a future gold standard.}, }
@article {pmid11871824, year = {2002}, author = {Akimaru, K and Onda, M and Tajiri, T and Yoshida, H and Yokomuro, S and Mamada, Y and Taniai, N and Yoshioka, M and Mineta, S}, title = {Middle hepatic vein reconstruction using a peritoneal patch: report of a case.}, journal = {Surgery today}, volume = {32}, number = {1}, pages = {75-77}, doi = {10.1007/s595-002-8119-5}, pmid = {11871824}, issn = {0941-1291}, mesh = {Aged ; Hepatic Veins/*surgery ; Humans ; Liver Neoplasms/secondary/surgery ; Male ; Peritoneum/*transplantation ; Plastic Surgery Procedures/methods ; Sigmoid Neoplasms/pathology ; }, abstract = {A 67-year-old male complaining of constipation with a change in stool caliber for several months visited our hospital in June 1999. A positive test for occult blood in the feces led to the disclosure of a type II carcinoma of the sigmoid colon with multiple liver metastases. A lymph node dissection with a sigmoidectomy disclosed no metastases histologically, so a left hepatectomy and enucleations of the metastases were performed. In addition, the invaded middle hepatic vein (MHV) was resected and repaired using a peritoneal patch. The patient's postoperative course was uneventful until July 2000, when computed tomography of the liver showed a single nodule measuring 3 cm in diameter in segment 6. The metastasis was excised in August. Since then, the patient has shown normal tumor marker values. The MHV has remained patent for 24 months after its reconstruction. A resection of the liver metastases including venous reconstruction is beneficial for patients since it results in a longer survival and allows for venous drainage of the residual liver. The peritoneum is also accessible, enabling the fitting of a patch graft for hepatic vein repair.}, }
@article {pmid11867957, year = {2002}, author = {Turkcapar, N and Kutlay, S and Nergizoglu, G and Atli, T and Duman, N}, title = {Prevalence of Cryptosporidium infection in hemodialysis patients.}, journal = {Nephron}, volume = {90}, number = {3}, pages = {344-346}, doi = {10.1159/000049072}, pmid = {11867957}, issn = {1660-8151}, mesh = {Adult ; Animals ; Cryptosporidiosis/complications/*epidemiology ; Cryptosporidium/cytology ; Feces/parasitology ; Female ; Humans ; Kidney Failure, Chronic/*complications ; Male ; *Renal Dialysis ; }, abstract = {The prevalence of Cryptosporidium infection in patients who are on chronic hemodialysis due to end-stage renal failure is investigated and compared with the incidence in the healthy population. Stool specimens of 74 adult hemodialysis patients treated on an outpatient basis and 50 healthy individuals are examined for Cryptosporidium oocysts by using the modified acid-fast method. While 20.27% (15/74) of patients in the dialysis group had Cryptosporidium oocysts in their stools, none (0/50) of the controls had such an infection (p < 0.001). Ten of 15 patients who had Cryptosporidium oocysts in their stool specimens were asymptomatic and the remaining 5 had diarrhea. Four of these 5 diarrheic patients had Cryptosporidium oocysts in their stools and 1 had both Cryptosporidium oocysts and Giardia trophozoites. Since hemodialysis patients with chronic renal failure are candidates for renal transplantation, general preventive measures against infection must be taken and these patients must be screened for their carrier state before transplantation.}, }
@article {pmid11858156, year = {2001}, author = {Bresson-Hadni, S and Vuitton, DA}, title = {[Echinococcoses].}, journal = {La Revue du praticien}, volume = {51}, number = {19}, pages = {2091-2098}, pmid = {11858156}, issn = {0035-2640}, mesh = {Abdominal Pain/parasitology ; Albendazole/therapeutic use ; Anticestodal Agents/therapeutic use ; Biopsy, Needle ; Combined Modality Therapy ; *Echinococcosis/complications/diagnosis/epidemiology/therapy ; Food Microbiology ; Hepatectomy ; Hepatomegaly/parasitology ; Humans ; Hygiene ; Jaundice/parasitology ; Liver Transplantation ; Pneumonectomy ; Prognosis ; Radiology, Interventional ; Tomography, X-Ray Computed ; Zoonoses ; }, abstract = {Human echinococcoses, cystic echinococcosis and alveolar echinococcosis are due to infections with the cestodes Echinococcus granulosus and E. multilocularis, respectively. Both zoonoses share a prolonged latency period before clinical presentation. However their evolution is fairly different: that of a begin tumor of the liver or lung for cystic echinoccocosis, and that of a slowly developing malignant tumor of the liver for alveolar echinoccocosis, with subsequent invasion of liver vessels and bile ducts and metastatic dissemination. Ultrasonography, CT-scan and specific serology are the key-exams for diagnosis. In both forms, surgery is the treatment of choice when a complete resection is possible. Liver transplantation may be an ultimate treatment option in very advanced cases of alveolar echinoccocosis. However, alternative treatment procedures have been proposed in the past 15 years and, combined with an earlier diagnosis, they have markedly improved patients survival and quality of life. Interventional radiology (puncture, aspiration, injection, reaspiration) has become a fully validated treatment of cystic echinoccocosis, and may be used in alveolar echinoccocosis for alleviating some of the complications of the disease such as biliary obstruction or bacterial superinfection. Albendazole, at high dosage, is a necessary complementary treatment after any intervention procedure, and for life when radical resection is not possible. Prevention relies on personal measures of hygiene and heating of contaminated food, and on collective measures aimed at reducing cestode egg shedding by the feces of infected canivores.}, }
@article {pmid11856125, year = {2002}, author = {Chapman, AE and Geerdes, B and Hewett, P and Young, J and Eyers, T and Kiroff, G and Maddern, GJ}, title = {Systematic review of dynamic graciloplasty in the treatment of faecal incontinence.}, journal = {The British journal of surgery}, volume = {89}, number = {2}, pages = {138-153}, doi = {10.1046/j.0007-1323.2001.02018.x}, pmid = {11856125}, issn = {0007-1323}, mesh = {Anal Canal/*surgery ; Animals ; Cost-Benefit Analysis ; Fecal Incontinence/*surgery ; Humans ; Muscle, Skeletal/*transplantation ; Muscle, Smooth/*transplantation ; Postoperative Complications/*etiology ; Reoperation ; Treatment Outcome ; }, abstract = {BACKGROUND: The aim of this systematic review was to compare the safety and efficacy of dynamic graciloplasty with colostomy for the treatment of faecal incontinence.<br><br>METHODS: Two search strategies were devised to retrieve literature from the Medline, Current Contents, Embase and Cochrane Library databases up until November 1999. Inclusion of papers depended on a predetermined protocol, independent assessments by two reviewers and a final consensus decision. English language papers were selected. Acceptable study designs included randomized controlled trials, controlled clinical trials and case series. Forty papers met the inclusion criteria. They were tabulated and critically appraised in terms of methodology and design, outcomes, and the possible influence of bias, confounding and chance.<br><br>RESULTS: No high-level evidence was available and there were no comparative studies. Mortality rates were around 2 per cent for both graciloplasty and colostomy. Morbidity rates reported for graciloplasty appear to be higher than those for colostomy. Dynamic graciloplasty was clearly effective at restoring continence in between 42 and 85 per cent of patients, whereas colostomy is, by its design, incapable of restoring continence. However, dynamic graciloplasty is associated with a significant risk of reoperation.<br><br>CONCLUSION: While dynamic graciloplasty appears to be associated with a higher rate of complications than colostomy, it is clearly a superior intervention for restoring continence in some patients. It is recommended that a comparative, but non-randomized, study be undertaken to evaluate the safety of dynamic graciloplasty in comparison to colostomy, and that the procedure should be performed only in centres where it is carried out routinely.}, }
@article {pmid11843370, year = {2002}, author = {Rathor, AM and Singh, R and Ramji, S and Tripathi, R}, title = {Randomised trial of amnioinfusion during labour with meconium stained amniotic fluid.}, journal = {BJOG : an international journal of obstetrics and gynaecology}, volume = {109}, number = {1}, pages = {17-20}, doi = {10.1111/j.1471-0528.2002.01140.x}, pmid = {11843370}, issn = {1470-0328}, mesh = {Adult ; Amnion/*transplantation ; Cesarean Section/statistics &amp; numerical data ; Extraction, Obstetrical/statistics &amp; numerical data ; Female ; Fetal Distress/prevention &amp; control ; Fever/etiology ; Humans ; Infant, Newborn ; Meconium/*chemistry ; Meconium Aspiration Syndrome/prevention &amp; control ; Pregnancy ; Pregnancy Outcome ; Prospective Studies ; Puerperal Disorders/etiology ; Risk Factors ; }, abstract = {OBJECTIVE: To assess the effect of amnioinfusion during labour with meconium stained amniotic fluid on caesarean section rate and perinatal outcome.<br><br>DESIGN: Prospective randomised controlled study.<br><br>SETTING: A tertiary care teaching hospital in India.<br><br>POPULATION: Women in labour at term with meconium stained amniotic fluid.<br><br>METHODS: Two hundred women in labour with > or = 37 weeks gestation, single cephalic presentation with moderate or thick meconium were randomised to control and amnioinfusion groups at a 1:1 ratio. Amnioinfusion was performed using 500 mL of normal saline over a period of 30 minutes in a study group. The control group received routine care. Both groups had intermittent auscultation of fetal heart rate during labour.<br><br>MAIN OUTCOME MEASURES: The primary outcome measure was caesarean section rate. Secondary outcome measures were meconium aspiration syndrome, 1 minute and 5 minute apgar < 7, hypoxic ischaemic encephalopathy, neonatal intensive care unit admission, meconium at the level of vocal cords.<br><br>RESULTS: The caesarean section rate in the amnioinfusion group was less than the control group (RR 0.47; 95% CI 0.24-0.93). Amnioinfusion was associated with a significant decrease in the incidence of meconium at the vocal cords (P = 0.001); improvement in 1 minute apgar scores (P < 0.05), respiratory distress (P = 0.002) and fewer admissions to nursery compared with the controls. This sample size was inadequate to study the impact on meconium aspiration syndrome.<br><br>CONCLUSION: Amnioinfusion in an under resourced labour ward decreases caesarean section rates and fetal morbidity.}, }
@article {pmid11843042, year = {2002}, author = {Barone, M and Berloco, P and Ladisa, R and Ierardi, E and Caruso, ML and Valentini, AM and Notarnicola, M and Di, LA and Francavilla, A}, title = {Demonstration of a direct stimulatory effect of bile salts on rat colonic epithelial cell proliferation.}, journal = {Scandinavian journal of gastroenterology}, volume = {37}, number = {1}, pages = {88-94}, doi = {10.1080/003655202753387419}, pmid = {11843042}, issn = {0036-5521}, mesh = {Animals ; Apoptosis/drug effects/physiology ; Bile Acids and Salts/analysis/*pharmacology ; Colon/*drug effects/pathology/*physiopathology ; Colonic Neoplasms/etiology/pathology/*physiopathology ; Disease Models, Animal ; Epithelial Cells/*drug effects/pathology/*physiology ; Intestinal Mucosa/drug effects/pathology/physiopathology ; Male ; Rats ; Risk Factors ; Stimulation, Chemical ; }, abstract = {BACKGROUND: Despite the clear demonstration that an increase in faecal bile salt concentration can augment colonocyte proliferation, it is still controversial whether bile salts act on these cells as direct mitogens or by inducing a damage-related proliferative response. The goal of this study was to define the mechanism mediating the proliferative effect of bile salts on rat colonocytes.<br><br>METHODS: Faecal bile salt concentration was increased by feeding rats on diets enriched with either bile salts or fats. Colonic mucosa proliferating cell nuclear antigen (PCNA) expression, histology and apoptosis, and faecal water cytolytic activity were evaluated to assess proliferation and direct or indirect signs of mucosal damage.<br><br>RESULTS: Compared to standard diet, chenodeoxycholate-, deoxycholate- and fat-enriched diets produced a significant increase in both faecal water total bile salt concentration (46.0 versus 124.1, 145.9 and 498.5 micromol/L, respectively) and percentage of PCNA-positive nuclei (30.5, versus 37.7, 33.9 and 47.1, respectively) that appeared significantly correlated (r = 0.8; P < 0.001). Chenodeoxycholate and deoxycholate fed animals showed colonic mucosa histology and faecal water cytolytic activity similar to controls, with a significantly reduced apoptotic index. Rats fed on high fat diet, however, showed a mild inflammatory infiltrate associated with an increased apoptosis and faecal water cytolytic activity, all conditions not apparently determined by the increased faecal water total bile salt concentration.<br><br>CONCLUSIONS: The results obtained in this study demonstrate that bile salts act as direct mitogens on colonic epithelial cells.}, }
@article {pmid11810497, year = {1999}, author = {Hirakata, Y and Ishii, Y and Nakano, M and Matsuda, J and Ozaki, Y and Mochida, C and Iori, F and Ma, L and Izumikawa, K and Yamaguchi, T and Miyazaki, Y and Maesaki, S and Tomono, K and Yamada, Y and Yamaguchi, K and Kamihira, S and Kohno, S}, title = {Two sporadic cases of infections due to Klebsiella pneumoniae resistant to expanded-spectrum cephalosporins in Japan.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {5}, number = {2}, pages = {91-96}, doi = {10.1007/s101560050015}, pmid = {11810497}, issn = {1437-7780}, abstract = {TEM- or SHV-type extended-spectrum beta-lactamases (ESBLs) are of clinical concern in Europe and the United States, whereas bacterial strains producing such types of ESBLs have not been reported in Japan. We report here two cases of infection due to Klebsiella pneumoniae resistant to extended-spectrum cephalosporins in Japan. A ceftadizime-resistant K. pneumoniae strain (minimum inhibitory concentration; 32 &amp;mgr;g/ml) was isolated transiently from the sputum of an 87-year-old woman with acute myocardial infarction and pneumonia (patient 1). Ceftadizime-susceptible and -resistant (minimum inhibitory concentration; >/=8 &amp;mgr;g/ml) K. pneumoniae strains were isolated over a month from the blood, ascites, and feces of a 44-year-old man after bone marrow transplantation for acute lymphoblastic leukemia (patient 2); this patient died of K. pneumoniae sepsis and peritonitis followed by multiple organ failure. These isolates produced penicillinase, which was inhibited by clavulanic acid. A polymerase chain reaction (PCR) study showed that both isolates carried the SHV or LEN genes, but not the TEM, Toho-1, and IMP-1 genes. The pulsed-field gel electrophoresis profile of the strain isolated from patient 1 was genetically distinguishable from the profiles of the strains isolated from patient 2. It appeared that mutation of the beta-lactamase gene may have occurred in the body of patient 2, since the genotypes of the ceftadizime-susceptible and -resistant isolates from this patient were identical. Another 12 strains of K. pneumoniae, isolated from other patients in the same wards during the period in which the K. pneumoniae strains were isolated from patients 1 and 2, did not produce ESBLs and showed different genotypes. The results suggest that these isolates of resistant K. pneumoniae did not spread by cross transmission in the hospital and that the two cases were sporadic. Surveillance of these types of resistant bacteria is necessary, since they may well be present in other hospitals in Japan. Although the organisms are suspected to produce SHV-type ESBLs or LEN-1 variant beta-lactamases, further studies are necessary to specify the resistance genes.}, }
@article {pmid11760901, year = {2001}, author = {Seccia, M and Banti, P and Zocco, G and Viacava, P}, title = {Restoration of fecal continence with chronic electrostimulation of gracilis muscle 17 years after a Pickrell's operation.}, journal = {International journal of colorectal disease}, volume = {16}, number = {6}, pages = {391-394}, doi = {10.1007/s003840100330}, pmid = {11760901}, issn = {0179-1958}, mesh = {Adult ; Anus, Imperforate/complications/diagnosis/*surgery ; Electric Stimulation Therapy/*instrumentation/methods ; Electrodes, Implanted ; Fecal Incontinence/complications/diagnosis/*surgery ; Female ; Follow-Up Studies ; Humans ; Long-Term Care ; Muscle, Skeletal/*transplantation ; Postoperative Complications/*therapy ; Recovery of Function ; Surgical Procedures, Operative/adverse effects/methods ; Time Factors ; Treatment Outcome ; }, abstract = {A 27-year-old woman who had undergone a Pickrell's operation at the age of 10 years, was observed for severe incontinence to solid and liquid stools. Physical examination and physiological tests revealed poor resting anal tone but a very good response of the transposed gracilis to percutaneous electrostimulation, which showed that the gracilis ability to contract was maintained in spite of 17 years of only occasional and unplanned muscular activity. Examination also demonstrated that the muscle had followed body growth during the patient's development. Restoration of continence by continuous electrostimulation of the gracilis muscle was then planned. To allow muscular resistance to this stimulation a fast-to-slow twitch fiber conversion was first obtained by low-frequency electrostimulation. A subcutaneous abdominal implant of a pulse generator connected to the gracilis by intramuscular platinum-iridium electrodes was carried out. After a period of muscular training, fiber conversion was achieved, and continuous electrostimulation led to complete restoration of continence with stable results at the 36 month follow-up evaluation. This case demonstrates that even such a long period of muscular inactivity does not affect the possibility of recovering a failed Pickrell's operation using electrostimulation. This easy and safe procedure can be applied to all previously failed graciloplasties provided that muscle contractility is maintained.}, }
@article {pmid11746556, year = {2001}, author = {Stadelmann, WK and Bardoel, JW and Perez-Abadia, G and Majzoub, RK and Maldonado, C and Tobin, GR and Kon, M and Barker, JH}, title = {Dynamic rectus abdominis muscle flap for intestinal stomal continence: a systematic approach.}, journal = {Microsurgery}, volume = {21}, number = {6}, pages = {248-255}, doi = {10.1002/micr.1048}, pmid = {11746556}, issn = {0738-1085}, mesh = {Abdominal Muscles/*transplantation ; Animals ; Cadaver ; Disease Models, Animal ; Dogs ; Electric Stimulation/methods ; Feasibility Studies ; Fecal Incontinence/*prevention &amp; control ; Female ; Follow-Up Studies ; Humans ; Ileum/*surgery ; Male ; Plastic Surgery Procedures/*methods ; Sensitivity and Specificity ; *Surgical Flaps ; Surgical Stomas/*adverse effects ; Swine ; Treatment Outcome ; }, abstract = {Several attempts to create a continent stomal sphincter using dynamic myoplasty with limited success have been reported. Denervation atrophy and early muscle fatigue have plagued all reported attempts to make a continent stoma a reality. To address this problem in a series of experiments, we designed a stomal sphincter using the most caudal segment of the rectus abdominis muscle. Then, we performed a study to determine whether a sphincter created with a rectus abdominis muscle island flap could maintain stomal continence in the short term. We found that when stimulated using two different electrical stimulation protocols, in all cases the rectus abdominis muscle sphincter generated peak pressures well above those needed to maintain stomal continence (60 mm Hg). All sphincters were able to maintain stomal continence at all intraluminal bowel pressures tested. We found one of these protocols to be far superior and reached 4 hours of stomal continence after 8 to 10 weeks of electrical stimulation.}, }
@article {pmid11746553, year = {2001}, author = {Baeten, CG and Uludag O, O and Rongen, MJ}, title = {Dynamic graciloplasty for fecal incontinence.}, journal = {Microsurgery}, volume = {21}, number = {6}, pages = {230-234}, doi = {10.1002/micr.1045}, pmid = {11746553}, issn = {0738-1085}, mesh = {Adolescent ; Adult ; Aged ; Combined Modality Therapy ; Electric Stimulation/instrumentation/methods ; Electrodes ; Fecal Incontinence/*diagnosis/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Microsurgery/*methods ; Middle Aged ; Muscle, Skeletal/*transplantation ; Patient Satisfaction ; Plastic Surgery Procedures/methods ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {Fecal incontinence is a socially incapacitating condition with associated high treatment costs. The most common cause of fecal incontinence is trauma during childbirth followed by surgical interventions. After unsuccessful conventional treatment, muscle transposition is the next treatment option. Two local muscles are used for this purpose: the gluteus and the gracilis muscles. With both muscles, long-term muscle contractions are difficult to maintain due to muscle fatigue. The gracilis muscle, however, is technically much easier to transfer and most activities of daily living and even sports are still possible. Experimental studies have shown that electrical stimulation of skeletal muscles can transform fatigue-prone muscles into fatigue-resistant muscles. In 1986, we started to perform graciloplasty procedures with intramuscular electrodes connected to an electrical stimulator. To date, 200 patients have been treated in our institution using dynamic graciloplasty. All patients had severe incontinence without control of liquid or solid feces, most of them had previously received unsuccessful treatment using other techniques. The mean age was 48 years, the average time that patients had been incontinent was 12.4 years, and the cause of incontinence were trauma (n = 99), congenital (n = 28), pudendopathy (n = 58), and low motor neurological lesions (n = 15). Of these patients, 76% were considered to have successful outcomes. Patients whose cause of incontinence was trauma or pudendopathy tended to respond better to this treatment than patients with anal atresia.}, }
@article {pmid11732132, year = {2001}, author = {Churchill, BM and Abramson, RP and Wahl, EF}, title = {Dysfunction of the lower urinary and distal gastrointestinal tracts in pediatric patients with known spinal cord problems.}, journal = {Pediatric clinics of North America}, volume = {48}, number = {6}, pages = {1587-1630}, doi = {10.1016/s0031-3955(05)70393-x}, pmid = {11732132}, issn = {0031-3955}, mesh = {Biophysical Phenomena ; Biophysics ; Child ; Colon/innervation/physiology ; Colonic Diseases/*etiology/physiopathology/therapy ; Humans ; Rectal Diseases/*etiology/physiopathology/therapy ; Rectum/innervation/physiology ; Spinal Cord Diseases/*complications/therapy ; Urethra/innervation/physiology ; Urethral Diseases/diagnosis/*etiology/physiopathology/therapy ; Urinary Bladder/innervation/physiology ; Urinary Bladder Diseases/diagnosis/*etiology/physiopathology/therapy ; }, abstract = {Destruction of the urinary tract in children with elimination, storage, and holding dysfunction of the lower urinary and the distal GI tracts is caused primarily by high intravesical pressure. UTI accelerates this process. The LPP and the status of the urethral control mechanism and its relationship to the detrusor are the primary determinants of intravesical pressure. Intravesical pressures of more than 40 cm H2O are dangerous because they cause a pressure gradient that is transmitted proximally to the renal papillae, which results in the cessation of renal blood flow and a loss of renal function over time. Hydroureteronephrosis, VUR, UTI, urinary incontinence, and calculi formation also may occur. If these dangerously high intravesical pressures remain untreated, renal failure is likely to occur over time. These children then require dialysis or renal transplantation to survive, which is tragic and represents an enormous economic cost to society. Renal failure and upper urinary tract damage is nearly 100% preventable with early and appropriate evaluation and treatment. CIC is a crucial part of the management of these children and has been shown to be safe and effective, even in newborn boys. The use of the Credé maneuver (i.e., manual compression) to empty the bladder is obsolete and should be abandoned. The distal GI tract is inseparable from the lower urinary tract and must be treated simultaneously. Failure to treat the distal GI tract yields poor clinical results and much patient dissatisfaction and makes it difficult or impossible to treat the child's urinary tract problem successfully. Bowel-management programs must include daily high water and fiber intake, together with digital perianal stimulation or fecal extraction. Neuropathic bladder and bowel problems that are intractable to conservative medical and mechanical (i.e., CIC and digital perianal stimulation or fecal extraction, respectively) management almost always can be corrected surgically with high success rates in cooperative patients. Finally, neuropathic bladder and bowel problems can be extremely isolating and debilitating problems. Psychologic counseling and emotional support must be provided as needed. The care that these patients receive must be organized, comprehensive, and correlated with these patients' lifestyles. If these children are evaluated and treated early, they have the potential to live long, healthy, and productive lives.}, }
@article {pmid11729384, year = {2001}, author = {Z'graggen, K and Maurer, CA and Birrer, S and Giachino, D and Kern, B and Büchler, MW}, title = {A new surgical concept for rectal replacement after low anterior resection: the transverse coloplasty pouch.}, journal = {Annals of surgery}, volume = {234}, number = {6}, pages = {780-5; discussion 785-7}, pmid = {11729384}, issn = {0003-4932}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anal Canal/*surgery ; Anastomosis, Surgical/methods ; Colon/*surgery ; Digestive System Surgical Procedures/methods ; Fecal Incontinence/etiology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Postoperative Complications ; Prospective Studies ; Rectal Neoplasms/surgery ; Rectum/*surgery ; Surgical Staplers ; }, abstract = {OBJECTIVE: To analyze the feasibility, safety, complication and death rates, and early functional results of the transverse coloplasty pouch procedure after low anterior rectal resection and total mesorectal excision.<br><br>SUMMARY BACKGROUND DATA: The authors previously developed a novel neorectal reservoir, the transverse coloplasty pouch, in an animal model; they report the first clinical data of a prospective phase 1 study.<br><br>METHODS: Forty-one patients underwent low anterior rectal resection with total mesorectal excision for rectal cancer (n = 37) or benign pathology (n = 4). The continuity was restored with a transverse coloplasty pouch anastomosis, and the colon was defunctionalized for 3 months. Patients were followed up at 2-month intervals for functional outcome.<br><br>RESULTS: Intraoperative complications occurred in three patients (7%), none related to the transverse coloplasty pouch. There were no hospital deaths and the total complication rate was 27% (11/41); an anastomotic leakage rate of 7% was recorded. The stool frequency was 3.4 per 24 hours at 2 months follow-up and gradually decreased to 2.1 per 24 hours at 8 months. Stool dysfunctions such as stool urgency, fragmentation, and incontinence grade 1 and 2 were regularly observed until 6 months; the incidence significantly decreased thereafter. None of the patients had difficulties in pouch evacuation.<br><br>CONCLUSIONS: The transverse coloplasty pouch is a small-volume reservoir that can safely be used for reconstruction after sphincter-preserving rectal resection. The early functional outcome is favorable and can be compared to other colonic reservoirs. The concept of reducing early dysfunction seen after straight coloanal anastomosis and avoiding long-term problems of pouch evacuation is supported by this study. Future trials will compare the transverse coloplasty pouch with other techniques of restorative resections of the rectum.}, }
@article {pmid11711735, year = {2001}, author = {Majzoub, RK and Bardoel, JW and Ackermann, D and Maldonado, C and Barker, J and Stadelmann, WK}, title = {Analysis of chronic morphologic changes of small bowel in electrically stimulated canine island-flap rectus abdominis muscle stomal sphincters.}, journal = {Diseases of the colon and rectum}, volume = {44}, number = {11}, pages = {1630-1639}, doi = {10.1007/BF02234383}, pmid = {11711735}, issn = {0012-3706}, mesh = {Animals ; Disease Models, Animal ; Dogs ; Electric Stimulation ; Electrodes ; Fecal Incontinence/pathology/*surgery/veterinary ; Fibrosis ; Ischemia/*pathology ; Muscle Contraction/physiology ; Muscle, Skeletal/*transplantation ; Rectum/blood supply/surgery ; Surgical Flaps ; }, abstract = {PURPOSE: Dynamic myoplasty to achieve fecal continence has been used in humans with varying results. A potential complication of the use of dynamic skeletal sphincters to attain fecal continence is the development of ischemic strictures within the bowel encircled by the functional sphincter. This study examines the histologic changes present in the bowel wall used to create a functional dynamic island-flap stomal sphincter in a chronic canine model.<br><br>METHODS: The rectus abdominis muscles of canines were used to create island-flap stomal sphincters. Eight dynamic island-flap stomal sphincters were created from the rectus abdominis muscles in mongrel dogs by wrapping them around a blind loop of distal ileum that was no longer in continuity with the terminal small bowel. Temporary pacing electrodes were secured intramuscularly near the intercostal nerve entry point and connected to a subcutaneously placed pulse stimulator. Two different training protocols resulting in different contractile properties were used: Program A (n = 4) and Program B (n = 4). The island-flap sphincters were trained over 3 months to generate stomal intraluminal pressures of more than 60 mmHg in all animals. The intact sphincters, normal bowel, and contralateral stomal bowel were obtained when the animals were killed. Specimens were processed with paraffin embedding, sectioned, and stained with trichrome and hematoxylin-and-eosin stains. Measurements of the different bowel layers were made with a micrometer. The muscular sphincters were biopsied before and after training. Fiber-type histochemistry was performed with a monoclonal antibody to the fast isoforms of myosin. Pretrained and posttrained skeletal muscle specimens were examined histologically.<br><br>RESULTS: The bowel wall within the functional dynamic stomal sphincter did not exhibit any significant architectural changes related to ischemic fibrosis or mucosal damage. A significant fiber-type conversion was achieved in both training groups with Programs A and B, with a >50 percent conversion from fatigue-prone (type II) muscle fibers to fatigue-resistant (type I) muscle fibers. Biopsy specimens revealed that fiber-type transformation was uniform throughout the sphincters. Skeletal muscle fibers within both groups demonstrated a reduction in their fiber diameter. There was no evidence of significant fibrosis or deposition of fat within the skeletal muscle of the sphincters.<br><br>CONCLUSION: Results of our experiment suggest that our anterior abdominal wall dynamic island-flap stomal sphincter, which generates a contractile force over the bowel wall capable of producing enough stomal pressure to achieve fecal continence, is not intrinsically harmful to the bowel that it encircles. The transformation of skeletal muscle to fatigue-resistant (type I) fibers occurred uniformly throughout the skeletal muscle sphincters without evidence of muscle fiber damage or significant fibrosis.}, }
@article {pmid11692941, year = {2000}, author = {Kostov, D and Temelkov, T and Kiriazov, E and Ivanov, K and Ignatov, V and Kobakov, G}, title = {[Pseudocontinent colostomy - comparative experimental study].}, journal = {Khirurgiia}, volume = {56}, number = {5-6}, pages = {71-74}, pmid = {11692941}, issn = {0450-2167}, mesh = {Anal Canal/*surgery ; Animals ; Colostomy/*methods ; Dogs ; Fecal Incontinence/*prevention &amp; control ; Muscle, Smooth/*transplantation ; }, abstract = {The possibilities of smoothmuscle sphincteroplastic have been researched experimentally at 29 mongrel dogs. Six types smoothmuscle plastics have been studied--a method of Feodorov and Odariuc, a method of Musiani, a pylor as a sphincter, an own operative method in three versions. A comparatively research upon a functional fitness of the offered plastics and Schmidt's method has been done. The level of intraluminal pressure into the precolostomy segment of colon and a functional status of the taken out colostomy have been compared. The reliable lower level of intraluminal compression has been established (p < 0.05), using longitudinal muscle as a plastic material. The intraluminal pressure into the end segment of colon has been sustained raised, permanently, due to the tonus of circular muscle in to the transplant's wall. The degree of intraluminal compression seems to be directly proportional to the volume of stretching of smoothmuscle transplant (p < 0.001). There has been done a conclusion, that the smoothmuscle plastic gives operative-technical possibilities for raising of intraluminal pressure by changing the volume of stretching of the transplant.}, }
@article {pmid11692926, year = {2000}, author = {Kostov, D and Temelkov, T and Kiriazov, E and Ivanov, K and Kobakov, G and Ignatov, V}, title = {[A modified autotransplantation method providing for continence in preternatural anus].}, journal = {Khirurgiia}, volume = {56}, number = {5-6}, pages = {17-20}, pmid = {11692926}, issn = {0450-2167}, mesh = {Abdominal Muscles/surgery ; Anal Canal/*abnormalities/*surgery ; Colon/surgery ; Fecal Incontinence/*surgery/therapy ; Female ; Follow-Up Studies ; Humans ; Ileum/surgery ; Male ; Muscle, Smooth/transplantation ; Neoplasms/surgery ; Rectum/surgery ; Retrospective Studies ; }, abstract = {Over the period 1996 through 1998, a series of 58 patients undergo operation in the clinic of coloproctology--Medical University, Varna and in the clinic of surgery at the Naval Hospital--Varna, for continent preternatural anus formation on the anterior abdominal wall. A personal modification of Schmidt's (1978) method is used where a smooth-muscle cuff exerting pressure on the terminal segment of the large bowel, brought out as an artificial anus, is created. The operative procedure is combined with periodic colon irrigations in the postoperative period for the purpose of stimulating controlled intestinal content evacuation. The degree of continence is evaluated clinically and manometrically in all cases at termination of the first postoperative month, and in 31 of them--at the end of the second postoperative year. The early and late results are good.}, }
@article {pmid11687465, year = {2001}, author = {Yoo, D and Willson, P and Pei, Y and Hayes, MA and Deckert, A and Dewey, CE and Friendship, RM and Yoon, Y and Gottschalk, M and Yason, C and Giulivi, A}, title = {Prevalence of hepatitis E virus antibodies in Canadian swine herds and identification of a novel variant of swine hepatitis E virus.}, journal = {Clinical and diagnostic laboratory immunology}, volume = {8}, number = {6}, pages = {1213-1219}, pmid = {11687465}, issn = {1071-412X}, mesh = {Animals ; Antibodies, Viral/blood ; Base Sequence ; Canada/epidemiology ; Cross Reactions ; Gene Expression Regulation, Viral ; Genotype ; Hepatitis E/*epidemiology/immunology ; Hepatitis E virus/classification/genetics/*immunology ; Humans ; Molecular Sequence Data ; Phylogeny ; Seroepidemiologic Studies ; Swine ; Swine Diseases/*epidemiology/immunology/virology ; Viral Proteins/genetics/immunology ; Zoonoses ; }, abstract = {Swine hepatitis E virus is a newly identified potentially zoonotic virus from pigs of particular concern for possible direct transmission to a human xenotransplant recipient by organ transplantation. In the present study, prevalence of serum antibodies to hepatitis E virus was examined in Canadian swine herds. A total of 998 serum samples collected from 6-month-old healthy slaughter hogs were examined by enzyme immunoassay and Western blot analysis for antibodies to the recombinant open reading frame 3 (ORF3) protein of hepatitis E virus expressed in Escherichia coli. These samples represented more than 80 different swine production units from five major swine-producing provinces across Canada. From this study, 594 samples (59.4%) were found to be positive for hepatitis E virus antibody. The seroprevalence was higher in Quebec (88.8%) and Ontario (80.1%) than in Alberta and Saskatchewan (38.3%). By PCR using a pair of oligonucleotide primers deduced from the ORF2 sequence of human hepatitis E virus, a specific hepatitis E virus sequence was recovered from feces of pigs. The nucleotide sequence identity between the U.S. swine hepatitis E virus and the Canadian isolate (SK3) was only 85.8%, suggesting that genotypic variations may exist in swine hepatitis E virus in North America. Among 165 serum samples collected from humans in Saskatchewan, 2.4% were found to be positive for antibodies to the hepatitis E virus ORF3 protein. Our data indicate that hepatitis E virus is highly prevalent in commercial swine populations in Canada and support the suggestion that the swine hepatitis E virus may be an important zoonotic agent for humans.}, }
@article {pmid11683746, year = {2001}, author = {Altomare, DF and Rinaldi, M and Sallustio, PL and Martino, P and De Fazio, M and Memeo, V}, title = {Long-term effects of stapled haemorrhoidectomy on internal anal function and sensitivity.}, journal = {The British journal of surgery}, volume = {88}, number = {11}, pages = {1487-1491}, doi = {10.1046/j.0007-1323.2001.01898.x}, pmid = {11683746}, issn = {0007-1323}, mesh = {Adult ; Aged ; Air ; Anus Diseases/diagnostic imaging/*physiopathology ; Fecal Incontinence/etiology/physiopathology ; Female ; Hemorrhoids/*surgery ; Humans ; Male ; Manometry ; Middle Aged ; Pressure ; Prospective Studies ; Sensation/physiology ; Surgical Stapling/*methods ; Ultrasonography ; Water ; }, abstract = {BACKGROUND: Stapled haemorrhoidectomy is gaining wide acceptance but there is still some concern about the risk of injury to the internal anal sphincter (IAS). IAS function and morphology, and anal canal sensitivity were studied prospectively in patients undergoing this operation.<br><br>METHODS: Twenty patients (11 women; mean age 43 years) with stage III haemorrhoids entered the study. All underwent preoperative anorectal manometry, rectoanal inhibitory reflex (RAIR) testing and three-dimensional transanal ultrasonography. A test of anal sensation was administered to evaluate ability to discriminate between air and warm water. All the investigations were repeated 6 months after the operation.<br><br>RESULTS: The mean(s.d.) maximal resting pressure was 87(30) mmHg before surgery and 81(20) mmHg afterwards (P not significant). The maximal squeeze pressure did not change after operation (178(43) versus 174(60) mmHg). The RAIR showed the same features in 19 of 20 patients before and 18 of 20 after operation. Three-dimensional ultrasonography demonstrated no changes in the width of the IAS (mean(s.d.) 2.1(4) mm before and 2.1(3) mm after surgery). The ability of the anal mucosa to discriminate air from warm water improved in five patients. Continence scores did not differ significantly after 6 months.<br><br>CONCLUSION: Stapled haemorrhoidectomy does not affect the function and morphology of the IAS in the long term. The sensitivity of the anal canal can improve in patients with preoperative sensory impairment.}, }
@article {pmid11683745, year = {2001}, author = {Altomare, DF and Dodi, G and La Torre, F and Romano, G and Melega, E and Rinaldi, M}, title = {Multicentre retrospective analysis of the outcome of artificial anal sphincter implantation for severe faecal incontinence.}, journal = {The British journal of surgery}, volume = {88}, number = {11}, pages = {1481-1486}, doi = {10.1046/j.0007-1323.2001.01895.x}, pmid = {11683745}, issn = {0007-1323}, mesh = {Adult ; Aged ; *Anal Canal ; Artificial Organs/*standards ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Manometry ; Middle Aged ; Pressure ; Prosthesis Implantation/methods/standards ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: A new prosthetic device, the Action artificial anal sphincter, has recently been introduced for treating severe faecal incontinence. The results of this procedure in 28 patients are presented.<br><br>METHODS: The patients underwent operation for severe faecal incontinence in four Italian university hospitals and patients were reviewed after a median follow-up of 19 (range 7-41) months.<br><br>RESULTS: Early infections occurred in four patients, requiring removal of the device in three. Dehiscence of the perineal wound occurred in nine patients. After activation of the device, the cuff had to be removed in a further four patients (for rectal erosion in two, anal pain in one and late infection in one). The cuff was accidentally broken in one patient. A new anal cuff was repositioned successfully in two patients. Overall, five patients had complete removal of the device and two removal of the cuff only. Twenty-one patients available for long-term evaluation had a major improvement in faecal continence. Median resting anal pressure increased from 27 mmHg before surgery to 32 mmHg after operation. Preoperative squeeze pressure was 42 mmHg while maximum postoperative anal pressure with the activated device was 67 mmHg. The median American Medical System incontinence score decreased significantly from 98.5 to 5.5 (P < 0.001). Similar figures were observed using the Continence Grading Scale (from 14.9 to 2.6; P < 0.001). Twelve patients developed symptoms of obstructed defaecation while two patients complained of anal pain.<br><br>CONCLUSION: Improved continence was achieved after neosphincter implantation in three-quarters of the patients. Early infection and rectal erosion, together with difficulty in evacuating, are still major concerns with this technique.}, }
@article {pmid11598470, year = {2001}, author = {Matzel, KE and Madoff, RD and LaFontaine, LJ and Baeten, CG and Buie, WD and Christiansen, J and Wexner, S and , }, title = {Complications of dynamic graciloplasty: incidence, management, and impact on outcome.}, journal = {Diseases of the colon and rectum}, volume = {44}, number = {10}, pages = {1427-1435}, doi = {10.1007/BF02234593}, pmid = {11598470}, issn = {0012-3706}, mesh = {Anal Canal/surgery ; Constipation ; *Digestive System Surgical Procedures/adverse effects/methods ; Electrodes, Implanted ; Equipment Failure ; Fecal Incontinence/*surgery ; Humans ; Muscle, Skeletal/transplantation ; Pain ; *Postoperative Complications/epidemiology ; Prospective Studies ; Reoperation ; Surgical Wound Infection ; Thromboembolism/etiology ; Wound Healing ; }, abstract = {PURPOSE: Dynamic graciloplasty can improve continence in patients with severe refractory fecal incontinence, but associated morbidity is high. The purpose of this study was to identify complications associated with dynamic graciloplasty and to characterize their treatment and impact on patient outcome.<br><br>METHODS: In 121 patients enrolled in a prospective trial of 20 centers and eligible for safety analysis, all complications of dynamic graciloplasty were recorded at the time of their occurrence and followed up until resolution. Severe treatment-related complications were defined as those requiring hospitalization or surgical intervention.<br><br>RESULTS: In 93 patients, 211 complications occurred. Of these, 89 (42 percent) in 61 patients were classified as severe treatment-related complications and resulted from the following: major infection, 19; minor infection, 10; thromboembolic events, 3; device performance and use, 13; pain, 16; noninfectious gracilis problems, 8; noninfectious wound-healing problems, 3; other surgery-related complications, 3. In addition, severe treatment-related complications resulted from constipation in ten and stoma creation or closure in ten. The recovery rate (full or partial) was 87 percent overall, and for severe treatment-related complications, was 92 percent. Of the types of complications, only major infections had an adverse effect on outcome.<br><br>CONCLUSION: Severe complications occur frequently after dynamic graciloplasty, but are usually treatable. They often require one or more reoperations and can lead to significant delays in completion of therapy. In most cases therapy can be salvaged.}, }
@article {pmid11594120, year = {2001}, author = {Hetzer, FH and Künzi, W and Demartines, N and Clavien, PA}, title = {[Fecal incontinence: therapy of congenital sphincter dysplasia in adulthood--a case report].}, journal = {Praxis}, volume = {90}, number = {35}, pages = {1471-1474}, pmid = {11594120}, issn = {1661-8157}, mesh = {Adult ; Anus, Imperforate/diagnosis/*surgery ; Electric Stimulation Therapy ; Fecal Incontinence/*congenital/surgery ; Female ; Humans ; Male ; Muscle, Skeletal/transplantation ; Postoperative Care ; Rectal Prolapse/congenital/surgery ; }, abstract = {The dynamic graciloplasty has gained acceptance in the therapy of intractable fecal incontinence. With a success-rate of 60 to 80%, the dynamic graciloplasty is a good alternative towards a permanent colostomy for individual cases. Furthermore, adults suffering from congenital anal atresia may be well treated by this therapy as described in this case. Following surgery, an accurate follow-up is inevitable in these patients, including training of neosphincter control. After 8 to 12 weeks the training-process of the neosphincter-control should be finished. At this point of time the patient will have obtained defecation-control and should be able to execute voluntary defecations.}, }
@article {pmid11591211, year = {2001}, author = {Muñòz, P and Palomo, J and Yáñèz, J and Bouza, E}, title = {Clinical microbiological case: a heart transplant recipient with diarrhea and abdominal pain. Recurring C. difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {7}, number = {8}, pages = {451-2, 458-9}, doi = {10.1046/j.1198-743x.2001.00315.x}, pmid = {11591211}, issn = {1198-743X}, mesh = {Abdominal Pain/etiology ; Adult ; *Clostridioides difficile ; Diarrhea/drug therapy/*microbiology ; Enterocolitis, Pseudomembranous/drug therapy/*microbiology ; Feces/chemistry/microbiology ; Graft Rejection/drug therapy/immunology ; Heart Transplantation/*adverse effects/immunology ; Humans ; Immunocompromised Host ; Male ; Metronidazole/therapeutic use ; Vancomycin/therapeutic use ; }, }
@article {pmid11584612, year = {2001}, author = {Francombe, J and Carter, PS and Hershman, MJ}, title = {The surgical management of faecal incontinence.}, journal = {Hospital medicine (London, England : 1998)}, volume = {62}, number = {9}, pages = {542-545}, doi = {10.12968/hosp.2001.62.9.1644}, pmid = {11584612}, issn = {1462-3935}, mesh = {Anal Canal/*surgery ; Fecal Incontinence/*surgery ; Humans ; Muscles/transplantation ; Pelvic Floor/*surgery ; Proctoscopy/methods ; Surgical Flaps ; }, abstract = {The surgical management of faecal incontinence is complex and technically demanding. Surgery should only be offered once the aetiology has been correctly identified and the patient has been counselled regarding outcomes of success. This may only approach 80%, with long-term results declining with time.}, }
@article {pmid11579296, year = {2001}, author = {Bakir, M and Bova, JL and Newell, KA and Millis, JM and Buell, JF and Arnow, PM}, title = {Epidemiology and clinical consequences of vancomycin-resistant enterococci in liver transplant patients.}, journal = {Transplantation}, volume = {72}, number = {6}, pages = {1032-1037}, doi = {10.1097/00007890-200109270-00009}, pmid = {11579296}, issn = {0041-1337}, mesh = {Adult ; Bacterial Infections/*epidemiology/microbiology/*physiopathology ; Bile/microbiology ; DNA, Bacterial/isolation &amp; purification ; Enterococcus/genetics/isolation &amp; purification/*physiology ; Environmental Microbiology ; Feces/microbiology ; Female ; Humans ; Incidence ; *Liver Transplantation ; Male ; Middle Aged ; Population Surveillance/methods ; *Vancomycin Resistance ; }, abstract = {BACKGROUND: Vancomycin-resistant enterococci (VRE) are increasingly important as pathogens in liver transplant patients. To guide control efforts, we conducted an epidemiological study of the frequency, source, and modes of transmission of VRE at our center.<br><br>METHODS: During September 1998 through August 1999, we obtained weekly surveillance cultures from consenting liver transplant patients and surfaces in their rooms. Pooled handwash specimens from personnel also were obtained. Specimens were processed on selective media to detect VRE, and isolates were typed by pulsed field gel electrophoresis. Information was collected from patient records concerning in-hospital treatment and clinical course.<br><br>RESULTS: Serial cultures were obtained during 33 admissions of 29 patients. VRE were detected in initial specimens from 6 admissions, and nosocomial acquisition of VRE occurred in 12 (44%) of the remaining 27 admissions. Seven different strain types of VRE were detected. The initial site of acquisition was stool in all cases; bile became culture-positive in only two patients. Overall, 16 (55%) of the 29 patients became colonized, usually after transplantation. VRE were detected in environmental cultures during 10 admissions and in 2 of 21 pooled handwashes. No statistically significant differences in clinical status or treatment were found when colonized patients were compared to noncolonized controls. The only VRE infection resulted from a choledochojejunostomy anastomotic leak.<br><br>CONCLUSION: Alimentary tract colonization by VRE occurred commonly in liver transplant patients, probably by cross-transmission. The clinical consequences were modest in the patients studied, but colonized transplant patients provide a substantial reservoir for continued VRE transmission in hospitals.}, }
@article {pmid11574596, year = {2001}, author = {Goto, K and Ishihara, KI and Kuzuoka, A and Ohnishi, Y and Itoh, T}, title = {Contamination of transplantable human tumor-bearing lines by Helicobacter hepaticus and its elimination.}, journal = {Journal of clinical microbiology}, volume = {39}, number = {10}, pages = {3703-3704}, pmid = {11574596}, issn = {0095-1137}, mesh = {Animals ; *Cryopreservation ; Feces/virology ; Helicobacter/genetics/*growth &amp; development/isolation &amp; purification ; Helicobacter Infections/*microbiology/transmission ; Humans ; Mice ; Mice, SCID ; *Neoplasm Transplantation ; Neoplasms, Experimental/*virology ; Polymerase Chain Reaction ; *Transplantation, Heterologous ; }, abstract = {Helicobacter hepaticus contaminating nonfrozen tumors was transmissible to severe combined immunodeficient (SCID) mice, but the organism in cryopreserved samples was not. This suggests that H. hepaticus has the ability to spread via biomaterials and that freezing-thawing is able to reduce the numbers of organisms to levels insufficient for subcutaneous infection of SCID mice.}, }
@article {pmid11560789, year = {2001}, author = {Kocoshis, S}, title = {Small Intestinal Failure in Children.}, journal = {Current treatment options in gastroenterology}, volume = {4}, number = {5}, pages = {423-432}, doi = {10.1007/s11938-001-0007-5}, pmid = {11560789}, issn = {1092-8472}, abstract = {The treatment of children with intestinal failure should be predicated upon three overriding goals: 1) to keep the patient well nourished by parenteral nutrition (TPN), 2) to minimize the fecal loss of fluid, electrolytes, and nutrients, and 3) to enhance the natural process of intestinal adaptation whenever possible. The first goal is relatively easy to accomplish in the short- or intermediate-term, but difficult to accomplish for more than a few years because of recurrent septicemia, loss of venous access, and cholestatic liver disease. The risks of sepsis and loss of venous access can be minimized through meticulous central line care and the use of appropriate antibiotics when indicated. Cycling TPN and limiting parenteral protein intake sometimes ameliorates cholestasis. The second goal is only partially achievable regardless of the cause of intestinal failure. Fluid and electrolyte secretion often can be reduced but not normalized with antisecretory drugs. Bacterial overgrowth can be treated with the judicious use of antibiotics. The third goal generally can be accomplished only in a subpopulation of patients with surgically created short bowel. In these children, a satisfactory increase in surface area can occur only if nutrients are delivered directly into the bowel lumen. The trophic effects of glutamine, growth hormone, and other hormones remain to be universally accepted. Surgical bowel lengthening or bowel tapering can sometimes enhance intestinal function among patients with short bowel syndrome. If medical or nontransplantation surgical management of intestinal failure is unsuccessful, and the patient develops irreversible TPN-associated complications, transplantation of the intestine should be strongly considered.}, }
@article {pmid11548548, year = {2001}, author = {Jevtović, D and Novaković, M and Gacević, M and Stepić, N and Prcović, M}, title = {[Transposition of the gracilis muscle in reconstruction of the anal sphincter].}, journal = {Vojnosanitetski pregled}, volume = {58}, number = {3}, pages = {243-248}, pmid = {11548548}, issn = {0042-8450}, mesh = {Adolescent ; Adult ; Anal Canal/*surgery ; Child ; Fecal Incontinence/etiology/*surgery ; Female ; Humans ; Leg ; Male ; Muscle, Skeletal/*transplantation ; Postoperative Complications ; }, abstract = {UNLABELLED: Fecal incontinence is a serious psychological and social problem for the patient, frequently leading to social isolation, loss of working potential and depression. Different static and dynamic methods for the reconstruction of anal sphincter are used in the surgical treatment of the incontinence. At the Clinic for Plastic Surgery and Burns, at the Military Medical Academy, we have been using the method of transposition of the gracilis muscle, previously described by Pickerill-Broadbent (1952) since 1970. The aim of this paper was to describe our results in the treatment of fecal incontinence with the gracilis muscle. We have operated on 14 patients: 5 with congenital absence of the anus, 2 with myelomeningocele, 2 with the teratoma in the sacral region, 2 with the injury after the surgical procedure in the anal region and 3 with war injuries in the perineal area. After the detailed clinical and neurological examinations and pre-surgical preparations, we have performed the operation using the already mentioned technique (Pickerill). The following postoperative complications were identified: one hematoma and two minor dehiscences of the perianal wounds that healed per secundam. The electrostimulations of the transposed gracilis muscle were performed postoperatively. All the operated patients have been followed up for three years after the operation. In 9 patients the result was estimated as the excellent, in 3 as affordable and in 2 as the poor (occasionally, they could not contain the liquid fecal incontinence)?<br><br>CONCLUSION: Due to its anatomical characteristics, the gracilis muscle is the most suitable for the reconstruction of the anal sphincter. If the correct indication is made, and if the surgery is well prepared and technically performed, with the maximal protection of neurovascular pedicle, an excellent postoperative result can be expected in over 60% cases.}, }
@article {pmid11528612, year = {2001}, author = {Han, SJ and Han, A and Choi, SH and Oh, JT and Hwang, EH}, title = {Biliary atresia associated with meconium peritonitis caused by perforation of small bowel atresia.}, journal = {Journal of pediatric surgery}, volume = {36}, number = {9}, pages = {1390-1393}, doi = {10.1053/jpsu.2001.26378}, pmid = {11528612}, issn = {0022-3468}, mesh = {Biliary Atresia/diagnosis/*etiology/therapy ; Female ; Humans ; Infant ; Infant, Newborn ; Intestinal Atresia/*complications/diagnosis/therapy ; Intestinal Perforation/*complications/diagnosis/therapy ; Intestine, Small/*abnormalities ; Male ; Meconium ; Peritonitis/diagnosis/*etiology/therapy ; Prognosis ; Retrospective Studies ; Risk Assessment ; Severity of Illness Index ; Survival Rate ; }, abstract = {BACKGROUND/PURPOSE: This report describes our experiences with 5 cases of biliary atresia associated with meconium peritonitis caused by perforation of small bowel atresia.<br><br>METHODS: A review of medical records was undertaken in an effort to recognize cases of biliary atresia associated with meconium peritonitis.<br><br>RESULTS: Five patients of 171 with biliary atresia (2.9%) were detected to have meconium peritonitis caused by perforation of small bowel atresia. The biliary atresia was not suspected during the initial operation for meconium peritonitis. Total parenteral nutrition (TPN) made it difficult to make an early differential diagnosis of biliary atresia because of the presence of TPN-associated cholestatic jaundice, and the Roux-en-Y limb used for hepatic portoenterostomy could not be made long enough to prevent cholangitis caused by preexisting short bowel. The main complications were severe, intractable cholangitis, short bowel syndrome with malnutrition; TPN-associated liver injury; and wound problems. Two patients died of ascending cholangitis, 1 patient of liver failure that was exacerbated by TPN-associated liver injury, and 1 patient is awaiting a liver transplant. Only 1 patient is in good health, being anicteric and showing normal growth and development.<br><br>CONCLUSIONS: Biliary atresia is evidently closely associated with meconium peritonitis caused by perforation of small bowel atresia. The management of these patients is more difficult than that of patients with the usual form of biliary atresia, because of the necessity for a long period of TPN and the combined short bowel syndrome. The ideal management of these conditions has yet to be determined.}, }
@article {pmid11525859, year = {2001}, author = {Potokar, T and Ramaswamy, R and Dickson, WA}, title = {Isolated buttock burns: epidemiology and management.}, journal = {Burns : journal of the International Society for Burn Injuries}, volume = {27}, number = {6}, pages = {629-634}, doi = {10.1016/s0305-4179(01)00024-9}, pmid = {11525859}, issn = {0305-4179}, mesh = {Accidents, Home ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Burns/epidemiology/etiology/pathology/*therapy ; Buttocks/*injuries ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Skin Transplantation ; Wales/epidemiology ; }, abstract = {This is a retrospective study of the epidemiology and management of isolated buttock burns presenting to the Welsh Regional Burns Centre from January 1996 to December 1999. A total of 36 cases have been treated of which 31 are included in this study. Approximately, 50% are in the paediatric age group and the sex distribution is equal for both adults and children. Contact burns form the largest group, and in children resulted in superficial burns requiring dressings only. The adult population is more likely to sustain deeper burns that require skin grafting, and approximately 50% will have a contributing premorbid condition. Despite difficulties in dressing and positioning of the patients, grafting of full thickness burns is appropriate without recourse to faecal diversion.}, }
@article {pmid11512055, year = {2001}, author = {Hochleitner, BW and Bösmüller, C and Nehoda, H and Frühwirt, M and Simma, B and Ellemunter, H and Steurer, W and Hochleitner, EO and Königsrainer, A and Margreiter, R}, title = {Increased tacrolimus levels during diarrhea.}, journal = {Transplant international : official journal of the European Society for Organ Transplantation}, volume = {14}, number = {4}, pages = {230-233}, doi = {10.1007/s001470100331}, pmid = {11512055}, issn = {0934-0874}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; Diarrhea/*metabolism ; Female ; Humans ; Immunosuppressive Agents/*pharmacokinetics ; Infant ; Kidney Transplantation ; Liver Transplantation ; Male ; Middle Aged ; Pancreas Transplantation ; Tacrolimus/*pharmacokinetics ; }, abstract = {While it is well known that diarrhea results in decreased trough levels of cyclosporin A, experience with levels of tacrolimus (FK506) and diarrhea is limited. We have therefore measured the tacrolimus trough levels of four male and two female recipients of solid organs before, during, and after gastroenteritis. The average age of these six patients was 31 (1-60) years. Four patients had received a kidney transplant, one patient had undergone simultaneous kidney-pancreas transplantation, and another patient had received a liver transplant. Rotavirus was identified in the feces specimen of a 1-year-old child that had undergone liver transplantation. All patients showed an elevated tacrolimus trough level (peak 20-60 ng/ml) after onset of gastroenteritis. Under symptomatic therapy and adequate adjustment of tacrolimus dose, the gastroenteritis stopped and tacrolimus levels returned to the therapeutic range. We recommend that FK506 levels be carefully monitored during diarrhea in order to prevent intoxication.}, }
@article {pmid11484264, year = {2000}, author = {Kostov, D and Temelkov, T and Kiriazov, E and Ivanov, K and Kobakov, G and Ignatov, V}, title = {[Continent preternatural anus--histomorphological and functional aspects].}, journal = {Khirurgiia}, volume = {56}, number = {1}, pages = {31-34}, pmid = {11484264}, issn = {0450-2167}, mesh = {Anal Canal/physiopathology/*surgery ; Electromyography ; Fecal Incontinence/*surgery ; Humans ; Intestine, Large/surgery ; Muscle, Smooth/*transplantation ; }, abstract = {Transplantation of a free smooth-muscular cuff around a terminal large-intestinal segment, brought out as preternatural anus, secures high-degree continence and controlled evacuatory rhythm of the intestinal content. The preserved structure of the muscular layers in the cuff wall and the myogenic nature of smooth muscle tone are preconditions for functional activity manifestation in conditions of denervation, isolation and even after block of neurons and intramural ganglia. Five preparations comprising the smooth muscle cuff and recipient large-intestinal segment undergo histomorphologic and electromyographic study within a year of transplantation. In a series of 31 patients with drawn out continent preternatural anus the thickness of the abdominal wall together with the smooth muscle cuff graft is echographically registered at the end of the first postoperative year. The echographically documented abdominal wall thickness is compared with the histomorphologically established values of the indicator under study. Analysis of the functional activity of the smooth-muscle-cuff transplant is also done.}, }
@article {pmid11445106, year = {2001}, author = {de Jong, MD and Weel, JF and van Oers, MH and Boom, R and Wertheim-van Dillen, PM}, title = {Molecular diagnosis of visceral herpes zoster.}, journal = {Lancet (London, England)}, volume = {357}, number = {9274}, pages = {2101-2102}, doi = {10.1016/s0140-6736(00)05199-0}, pmid = {11445106}, issn = {0140-6736}, mesh = {Abdominal Pain/*etiology/virology ; Adult ; Aged ; DNA, Viral/blood ; Feces/virology ; Female ; Hematopoietic Stem Cell Transplantation ; Herpes Zoster/*diagnosis ; Herpesvirus 3, Human/genetics/*isolation &amp; purification ; Humans ; *Immunocompromised Host ; Lymphoma, Non-Hodgkin/therapy ; Male ; Middle Aged ; Polymerase Chain Reaction ; }, abstract = {Patients with disseminated herpes zoster may present with severe abdominal pain that results from visceral involvement of varicella-zoster-virus infection. In the absence of cutaneous eruptions of herpes zoster, visceral herpes zoster is extremely difficult to diagnose. This diagnostic difficulty has the potential to cause devastating delays in treatment. We report a case series of four patients with visceral herpes zoster in whom large concentrations of DNA from varicella zoster virus were detectable in blood by PCR before signs of infection appeared on the skin, thus enabling early diagnosis and treatment.}, }
@article {pmid11431771, year = {2001}, author = {Rückauer, KD}, title = {Dynamic graciloplasty in children with fecal incontinence: a preliminary report.}, journal = {Journal of pediatric surgery}, volume = {36}, number = {7}, pages = {1036-1039}, doi = {10.1053/jpsu.2001.24733}, pmid = {11431771}, issn = {0022-3468}, mesh = {Child ; *Electric Stimulation Therapy ; Electrodes, Implanted ; Fecal Incontinence/etiology/*surgery ; Humans ; Male ; Muscle, Skeletal/*transplantation ; }, abstract = {BACKGROUND: Various therapeutic methods have been developed for anal incontinence. A reconstruction of the sphincter system with functional adaptation can be achieved by stimulation of the transposed gracilis muscle with an implanted stimulator.<br><br>METHODS: The authors performed a dynamic graciloplasty in 4 boys, aged between 6 and 10 years. Causes for the incontinence were polytrauma with pelvic rupture, VACTERL syndrome with rectal urethral fistula, anal atresia with primary reconstruction and 6 consecutive operations, and coccygeal teratoma in a premature infant with surgical treatment of the recurrent tumour. All children had grade III incontinence. Postoperatively, the duration of stimulation was increased successively by telemetric programming of the pulse generator up to a continuous mode.<br><br>RESULTS: One child is now almost continent, 2 show grade I incontinence, 1 is incontinent with frequent soiling (the programming has not been completed yet).<br><br>CONCLUSION: An evaluation of this method for children will not be possible until more operations have been performed, under the conditions of a prospective study, which appears indicated in view of the preliminary but encouraging results presented.}, }
@article {pmid11414415, year = {2000}, author = {Goh, YL and Puthucheary, SD and Thong, KL}, title = {Application of ribosomal RNA gene restriction patterns analysis and pulsed-field gel electrophoresis in distinguishing Salmonella weltevreden isolates in Malaysia.}, journal = {The Southeast Asian journal of tropical medicine and public health}, volume = {31}, number = {4}, pages = {697-701}, pmid = {11414415}, issn = {0125-1562}, mesh = {Base Sequence ; DNA Primers ; Electrophoresis, Gel, Pulsed-Field ; Feces/microbiology ; Gastroenteritis/microbiology ; Humans ; Malaysia ; Microbial Sensitivity Tests ; RNA, Ribosomal/*genetics ; Restriction Mapping ; Salmonella/drug effects/genetics/*isolation &amp; purification ; }, abstract = {A representative sample of 20 isolates of Salmonella weltevreden strains from stool cultures of patients admitted at the University Hospital, Kuala Lumpur, Malaysia were analyzed. All the strains were susceptible to ampicillin, ceftriaxone, ciprofloxacin, chloramphenicol, tetracycline, trimethoprim, gentamicin and co-trimoxazole. Ribosomal RNA gene restriction pattern analysis of PstI-digested DNA gave three ribotypes while pulsed-field gel electrophoresis (PFGE) analysis of XbaI-digested DNA gave ten distinct profiles. PFGE was more discriminative than ribotyping in distinguishing the strains. The majority of the strains analyzed were very closely related with similarity coefficient values ranging from 0.8 to 1.0. Both PFGE and ribotyping could distinguish one of the strains which was obtained from a patient following a bone marrow transplant for beta-thalassemia major, indicating that this particular strain was unrelated to the rest of the strains from patients with acute gastroenteritis.}, }
@article {pmid11331480, year = {2001}, author = {Cicalese, L and Rastellini, C and Sileri, P and Abcarian, H and Benedetti, E}, title = {Segmental living related small bowel transplantation in adults.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {5}, number = {2}, pages = {168-72; discussion 173}, pmid = {11331480}, issn = {1091-255X}, mesh = {Adult ; Female ; Graft Rejection ; Humans ; Ileum/*transplantation ; Immunosuppressive Agents/therapeutic use ; *Living Donors ; Male ; Middle Aged ; Parenteral Nutrition, Total ; Short Bowel Syndrome/*surgery ; }, abstract = {The advent of small bowel transplantation has provided selected patients with chronic intestinal irreversible failure with a physiologic alternative to total parenteral nutrition. Recently a standardized technique for living related small bowel transplantation (LR-SBTx) has been developed. Three patients with short bowel syndrome underwent LR-SBTx at our institution. All donors were ABO compatible with a good human leukocyte antigen match. A segment of 180 to 200 cm of ileum was harvested and transplanted with its vascular pedicle constituted by the ileocolic artery and vein. The grafts were transplanted with a short cold and warm ischemia time. The immunosuppression regimen consisted of oral FK-506, prednisone, and intravenous induction with atgam. Serial biopsies of the intestinal grafts were performed to evaluate rejection or viral infections. The postoperative course was uneventful for all donors. All of the recipients are currently alive and well. Two of three patients are off total parenteral nutrition and tolerating an oral diet with no limitations on daily activity. In the third patient, the graft was removed 6 weeks after transplantation. At the time of enterectomy, no technical or immunologic complications were documented. Absorption tests for D-xylose and fecal fat studies were performed showing functional adaptation of the segmental graft. All biopsies were negative for acute rejection. A well-matched segmental ileal graft from a living donor can provide complete rehabilitation for patients with short bowel syndrome. Our initial experience suggests that the risk of acute rejection and infection is greatly reduced compared to cadaveric bowel transplantation. Further clinical application of this procedure is warranted.}, }
@article {pmid11330587, year = {2001}, author = {Konsten, J and Rongen, MJ and Ogunbiyi, OA and Darakhshan, A and Baeten, CG and Williams, NS}, title = {Comparison of epineural or intramuscular nerve electrodes for stimulated graciloplasty.}, journal = {Diseases of the colon and rectum}, volume = {44}, number = {4}, pages = {581-586}, doi = {10.1007/BF02234333}, pmid = {11330587}, issn = {0012-3706}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/innervation/*surgery ; *Electric Stimulation ; *Electrodes, Implanted ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Middle Aged ; Muscle Fibers, Skeletal ; Muscles/innervation/transplantation ; Prospective Studies ; Retrospective Studies ; }, abstract = {OBJECTIVE: Two different techniques have been developed to stimulate the gracilis muscle when it is used in anal neosphincter reconstruction. These are direct neural stimulation and intramuscular electrode stimulation. The aim of this study was to compare these techniques.<br><br>METHODS: Comparison was made of gracilis anal neosphincter reconstruction using neural stimulation (Royal London Hospital in the United Kingdom) with the intramuscular muscular method (University Hospital Maastricht in the Netherlands). The United Kingdom data were obtained from a retrospective database, whereas the Netherlands data were gathered prospectively.<br><br>RESULTS: A successful outcome was achieved in 46 of 81 patients (57 percent) in London and 148 of 200 cases (74 percent) in the Maastricht study (chi-squared = 7.2; P < 0.01). There was no significant difference between the two techniques in voltage required for stimulation of the neosphincter muscle during a ten-year period. Reoperative surgery for electrode failure or dislocation was required in 21 (26 percent) patients in the London study, whereas only four (2.7 percent) of the Maastricht cases required such procedures (chi-squared = 37.8; P < 0.05). The high electrode plate failure rate in the London study was related to the source of manufacture.<br><br>CONCLUSIONS: Both neural and intramuscular nerve techniques provide effective long-term stimulation of the gracilis anal neosphincter.}, }
@article {pmid11328545, year = {2001}, author = {Frühwirth, M and Fischer, H and Simma, B and Hochleitner, B and Königsrainer, A and Margreiter, R and Ellemunter, H}, title = {Rotavirus infection as cause of tacrolimus elevation in solid-organ-transplanted children.}, journal = {Pediatric transplantation}, volume = {5}, number = {2}, pages = {88-92}, doi = {10.1034/j.1399-3046.2001.005002088.x}, pmid = {11328545}, issn = {1397-3142}, mesh = {Adult ; Child ; Diarrhea/*blood/*virology ; Drug Monitoring ; Feces/virology ; Female ; Gastroenteritis/blood/virology ; Humans ; Immunosuppressive Agents/administration &amp; dosage/*blood ; Infant ; Kidney Transplantation ; Liver Transplantation ; Lung Transplantation ; Male ; Postoperative Complications/*blood ; Rotavirus Infections/*blood ; Tacrolimus/administration &amp; dosage/*blood ; *Transplantation ; }, abstract = {Rotavirus (RV) is the most common cause of diarrheal illness in children. We report three solid-organ-transplanted patients in whom RV infection caused increased trough levels of the immunosuppressive macrolide tacrolimus (TAC) by mechanisms that are still under investigation. The virus was detected for longer in the feces of these patients than in infants not receiving immunosuppressive therapy. In association with short-term monitoring of blood trough levels of TAC, the dosage should be reduced early if symptoms of an acute gastroenteritis are present.}, }
@article {pmid11317698, year = {2001}, author = {Altomare, DF and Rinaldi, M and Veglia, A and Guglielmi, A and Sallustio, PL and Tripoli, G}, title = {Contribution of posture to the maintenance of anal continence.}, journal = {International journal of colorectal disease}, volume = {16}, number = {1}, pages = {51-54}, doi = {10.1007/s003840000274}, pmid = {11317698}, issn = {0179-1958}, mesh = {Adult ; Aged ; Anal Canal/*anatomy &amp; histology/*diagnostic imaging ; Confidence Intervals ; Constipation/diagnosis/*diagnostic imaging ; Defecation/physiology ; Defecography/*methods ; Fecal Incontinence/prevention &amp; control ; Female ; Humans ; Male ; Middle Aged ; *Posture ; Probability ; Sensitivity and Specificity ; }, abstract = {The anorectal angle (ARA) is believed to provide one of the most important contributions to anal continence. The normal resting angle is approx. 90 degrees, but the erect position may modify the ARA and other parameters usually considered in a proctometrogram. We compared the proctometrogram in different postures to elucidate the role of changes in the ARA in maintaining fecal continence. Sixty-three patients with constipation underwent static proctography. Variations in the ARA, perineal descent, puborectalis muscle length, and pubococcygeal distance were determined during resting, squeezing, and pushing with the patient in the Sims' position (SP); further evaluations used radiographs in resting position but with straight legs, in erect and sitting positions. The resting mean ARA was 95.3 +/- 15 degrees in SP and 79.8 +/- 14 degrees standing erect; the latter value was also significantly less during squeezing (84 +/- 11 degrees). The mean ARA during pushing was 118 +/- 16 degrees. A systematic and statistically significant difference in the mean resting ARA was demonstrated using the baseline of the rectal shape instead of the major rectal axis when measuring the anorectal angle. When sitting on a toilet, the mean resting ARA was significantly wider than in SP. The length of the puborectalis sling at rest did not change but was significantly reduced during squeezing and increased during pushing. The descent of the perineum at rest was near to 0 (-0.089 +/- 1.76 cm) in SP and significantly less when standing (-0.65 +/- 1.9 cm) and during squeezing (-0.97 +/- 1.7 cm). Perineal descent during pushing was +2.94 +/- 2.2 cm. The mean pubococcygeal distance did not change significantly in SP and in the erect position. The erect position thus contributes significantly to the maintenance of fecal continence by sharpening the ARA. This effect is stronger than any active contraction of the puborectalis muscle and is not related to shortening of the puborectalis sling but is secondary to lifting of the pelvic floor.}, }
@article {pmid11258438, year = {2001}, author = {Benedetti, E and Baum, C and Cicalese, L and Brown, M and Raofi, V and Massad, MG and Abcarian, H}, title = {Progressive functional adaptation of segmental bowel graft from living related donor.}, journal = {Transplantation}, volume = {71}, number = {4}, pages = {569-571}, doi = {10.1097/00007890-200102270-00014}, pmid = {11258438}, issn = {0041-1337}, mesh = {Adult ; Humans ; Ileum/*transplantation ; Living Donors ; Male ; Parenteral Nutrition ; Postoperative Period ; Short Bowel Syndrome/rehabilitation/surgery ; Transplantation, Homologous/physiology ; }, abstract = {We report a patient with short gut syndrome successfully treated with living related bowel transplantation. A 27-year-old Caucasian man was referred after traumatic loss of almost the entire bowel from the third portion of duodenum to the sigmoid colon. His HLA-identical sister volunteered as a donor. A 200-cm segment of ileum was successfully transplanted under tacrolimus-based immunosuppression. The posttransplant course was uneventful, without rejection or infectious complication. Total parenteral nutrition was discontinued 1 week posttransplant. At 6 months the patient had returned to his preinjury weight. Water and D-xylose absorption as well as fecal fat studies were markedly abnormal 1 month posttransplant but normalized by 6 months. The donor recovery was uneventful. A well-matched segmental ileal graft from living donor can provide complete rehabilitation for patients with short gut syndrome. We documented a progressive functional adaptation of the ileal graft, resulting in normal absorption by 5 months posttransplantation.}, }
@article {pmid11256256, year = {2001}, author = {Treviño, M and Prieto, E and Peñalver, D and Aguilera, A and García-Zabarte, A and García-Riestra, C and Regueiro, BJ}, title = {[Diarrhea caused by adenovirus and astrovirus in hospitalized immunodeficient patients].}, journal = {Enfermedades infecciosas y microbiologia clinica}, volume = {19}, number = {1}, pages = {7-10}, doi = {10.1016/s0213-005x(01)72540-2}, pmid = {11256256}, issn = {0213-005X}, mesh = {Adenoviridae Infections/diagnosis/*epidemiology/etiology/immunology ; Adenoviruses, Human/immunology/*isolation &amp; purification ; Adult ; Aged ; Antibodies, Viral/blood ; Astroviridae Infections/diagnosis/*epidemiology/etiology/immunology ; Child ; Comorbidity ; Cross Infection/diagnosis/epidemiology/immunology/*virology ; Diagnosis, Differential ; Diarrhea/diagnosis/epidemiology/etiology/immunology/microbiology/*virology ; Diarrhea, Infantile/epidemiology/immunology/*virology ; Enterocolitis, Pseudomembranous/epidemiology ; Feces/virology ; Female ; Graft Rejection/diagnosis ; HIV Infections/complications ; Humans ; Immunocompromised Host ; Immunologic Deficiency Syndromes/*complications ; Incidence ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology/immunology/*virology ; Inpatients ; Male ; Mamastrovirus/immunology/*isolation &amp; purification ; Middle Aged ; Neoplasms/epidemiology/immunology ; Postoperative Complications/diagnosis/epidemiology/immunology/virology ; Retrospective Studies ; Spain/epidemiology ; Superinfection ; Transplantation ; }, abstract = {BACKGROUND: Acute or chronic diarrheal illness are common complications in immunosuppressed patients such as human immunodeficiency virus (HIV)-infected, bone marrow or solid organ transplanted patients and those with leukaemias or other immune deficiency disorders. Due to the importance of recognizing the feasible etiologies of diarrhea in order to give the proper antimicrobial chemotherapy or to avoid a misdiagnosis of rejection in the case of transplanted patients, we have investigated adenovirus and astrovirus antigen in faeces from different immunosuppressed patients.<br><br>PATIENTS AND METHODS: Stool samples from 258 immunodeficient patients hospitalized at University Hospital Complex of Santiago of Compostela with acute or persistent diarrhea were collected between 1997-99 and assayed for astrovirus and adenovirus antigen. Viral antigen was detected by EIA. Other common enteric pathogens were also assayed.<br><br>RESULTS: Adenovirus antigen was positive in 5 cases (2%) and astrovirus antigen in 12 cases (5%). The most commonly patients infected was those with haematologic disorders and premature infants. HIV-infected patients were positive for astrovirus antigen in 3 cases. The majority of the cases were related with intestinal bacterial diseases or other circumstances, such as Clostridium difficile infection, both associated with prolonged antimicrobial therapy.<br><br>CONCLUSIONS: Astrovirus and adenovirus have to be considered as enteropathogens specially in immunocompromised hospitalized patients. An accurate diagnosis about diarrhea etiology is advisable in order to give a specific antimicrobial therapy, when it be necessary, or to avoid a misdiagnosis of rejection, in transplanted patients.}, }
@article {pmid11213083, year = {2001}, author = {Goetz, M and Eichenlaub, S and Pape, GR and Hoffmann, RM}, title = {Chronic diarrhea as a result of intestinal microsposidiosis in a liver transplant recipient.}, journal = {Transplantation}, volume = {71}, number = {2}, pages = {334-337}, doi = {10.1097/00007890-200101270-00029}, pmid = {11213083}, issn = {0041-1337}, mesh = {Adult ; Albendazole/therapeutic use ; Animals ; Chronic Disease ; Diarrhea/*etiology ; Feces/parasitology ; Female ; Humans ; Intestines/*parasitology ; Liver Transplantation/*adverse effects ; *Microsporida ; Microsporidiosis/*complications/drug therapy ; }, abstract = {BACKGROUND: Microsporidia are common pathogens among patients infected with human immunodeficiency virus. They account for a substantial proportion of chronic diarrhea and malabsorption in acquired immune deficiency syndrome, but their appearance after solid organ transplantation has only rarely been reported. Methods. We report what we believe is the first case of documented Enterocytozoon bieneusi infection in a liver transplant recipient. Results. Our patient presented with chronic diarrhea and colicky abdominal pain. Although symptoms were severe, only mild microscopical mucosal changes were found in the intestinal tract. A modified trichrome stain of stool specimens revealed microsporidial spores, and species differentiation by restriction fragment length polymorphism polymerase chain reaction identified Enterocytozoon bieneusi. Albendazole therapy brought symptomatic relief but no microbiological clearance.<br><br>CONCLUSIONS: Enterocytozoon bieneusi may cause chronic diarrhea not only in immunosuppression as a result of human immunodeficiency virus infection but also among patients with therapeutic immunosuppression after organ transplantation. Therefore, microsporidial infection should be considered in immunosuppressed patients with otherwise unexplained diarrhea.}, }
@article {pmid11208187, year = {2001}, author = {Mañez, R and Blanco, FJ and Díaz, I and Centeno, A and Lopez-Pelaez, E and Hermida, M and Davies, HF and Katopodis, A}, title = {Removal of bowel aerobic gram-negative bacteria is more effective than immunosuppression with cyclophosphamide and steroids to decrease natural alpha-galactosyl IgG antibodies.}, journal = {Xenotransplantation}, volume = {8}, number = {1}, pages = {15-23}, doi = {10.1034/j.1399-3089.2001.00082.x}, pmid = {11208187}, issn = {0908-665X}, mesh = {Animals ; Cyclophosphamide/administration &amp; dosage/immunology ; Disaccharides/*immunology ; Graft Rejection/immunology ; Gram-Negative Aerobic Bacteria/*immunology ; Haplorhini ; Humans ; Immunoglobulin G/immunology ; *Immunosuppression Therapy ; Immunosuppressive Agents/administration &amp; dosage/immunology ; Steroids/administration &amp; dosage/immunology ; Swine ; Transplantation, Heterologous/*immunology ; }, abstract = {Natural alpha-Galactosyl (Gal) antibodies play an important role in the rejection of pig xenografts by humans and Old World monkeys. In this study we investigate the efficacy of two different strategies to reduce the serum level of natural anti-Gal antibodies. On the one hand, removal of aerobic gram-negative bacteria from the intestinal flora, because anti-Gal antibodies appear to be produced as a result of the continuous sensitization by these microorganisms. On the other hand, we studied the effect on these antibodies of an immunosuppressive regimen of cyclophosphamide and steroids. Ten baboons were treated for three months with norfloxacin (Nor Group; n=6) or cyclophosphamide and steroids (CyP Group; n=4). A further four baboons did not receive any treatment (Control Group). Aerobic gram-negative bacteria became negative in stools of the Nor Group after two weeks of treatment, and remained undetectable until week 7. Thereafter, a gradual increase on the fecal concentration of aerobic gram-negative bacteria was observed despite the norfloxacin treatment. The mean anti-Gal IgG in the Nor Group gradually declined from week 4 to 9 to a mean of 62.7 +/- 18% of the baseline level, and during this period were significantly lower than in the CyP (P<0.02) and the Control (P<0.05) groups. No differences were observed between the three groups during the 16 weeks of follow-up in serum levels of anti-Gal IgM, hemolytic anti-pig antibodies, total IgG, IgM and IgA. In conclusion, removal of normal aerobic gram-negative bacteria from the intestinal flora is more effective than immunosuppression with CyP and steroids in reducing the level of natural anti-Gal antibodies, although there is no discernible effect on IgM antibodies.}, }
@article {pmid11169434, year = {2001}, author = {Brimnes, J and Reimann, J and Nissen, M and Claesson, M}, title = {Enteric bacterial antigens activate CD4(+) T cells from scid mice with inflammatory bowel disease.}, journal = {European journal of immunology}, volume = {31}, number = {1}, pages = {23-31}, doi = {10.1002/1521-4141(200101)31:1&lt;23::aid-immu23&gt;3.0.co;2-2}, pmid = {11169434}, issn = {0014-2980}, mesh = {Animals ; Antigen-Presenting Cells/physiology ; Antigens, Bacterial/*immunology ; CD4-Positive T-Lymphocytes/*immunology ; Germ-Free Life ; Histocompatibility Antigens Class II/physiology ; Inflammatory Bowel Diseases/*immunology ; Interferon-gamma/biosynthesis ; Interleukin-2/biosynthesis ; Intestines/*microbiology ; *Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, SCID ; Th1 Cells/immunology ; }, abstract = {Scid mice transplanted with CD4(+) T cells from congenic donor mice develop a chronic and lethal inflammatory bowel disease (IBD) 2-3 months post-transplantation. In the present study we have investigated the response of CD4(+) T cells from scid mice with colitis against fecal extracts. Our results show that in contrast to CD4(+) T cells from normal BALB/c mice, CD4(+) T cells from scid mice with colitis proliferate strongly in response to antigen-presenting cells (APC) pulsed with fecal extracts. The IBD-associated T cells did not respond to either extracts from food antigens or fecal extracts from germ-free mice, which indicates that they recognize bacterial antigens in the fecal extracts. CD4(+) T cells isolated from the colonic lamina propria of scid mice 3 weeks post transplantation also responded vigorously to fecal extracts, demonstrating that reactive CD4(+) T cells are present in the gut mucosa of transplanted scid mice prior to clinical manifestations of IBD. CD4(+) T cells activated by fecal extracts produced high amounts of IL-2 and IFN-gamma, intermediate amounts of IL-4 and low amounts of IL-10, consistent with a Th1 profile. The proliferative reactivity towards fecal extracts was restricted by MHC class II molecules and dependent on antigen processing, as the response could be blocked by anti-MHC class II antibodies or a short fixation of the APC. This study demonstrates that class II-restricted CD4(+) Th1 cells, which recognize enteric bacterial antigens, infiltrate the gut mucosa and spleen of transplanted scid mice prior to and during the course of colitis.}, }
@article {pmid11122175, year = {2000}, author = {Niriella, DA and Deen, KI}, title = {Neosphincters in the management of faecal incontinence.}, journal = {The British journal of surgery}, volume = {87}, number = {12}, pages = {1617-1628}, doi = {10.1046/j.1365-2168.2000.01605.x}, pmid = {11122175}, issn = {0007-1323}, mesh = {Anal Canal/physiology/*surgery ; *Artificial Organs ; Electric Stimulation ; Fecal Incontinence/*surgery ; Humans ; Muscle Contraction ; Muscle, Skeletal/blood supply/metabolism/transplantation ; Treatment Outcome ; }, abstract = {BACKGROUND: Surgical treatment of end-stage faecal incontinence has its origin in the early 1950s. Interest has been revived as a result of technical advances achieved in the recent past. The purpose of this article is to review the principles that underlie the use of skeletal muscle transposition around the anal canal and of electrical stimulation in the treatment of incontinence, and to explore new methods of treatment of this condition.<br><br>METHODS: A literature search was performed using Pubmed and Medline, employing keywords related to treatment of faecal incontinence by neosphincter reconstruction. Basic science and clinical aspects of neosphincter reconstruction were gathered from relevant texts, original articles and recently published abstracts.<br><br>RESULTS: The electrically stimulated gracilis neoanal sphincter seems to be the popular choice of biological neosphincter. It is more likely to produce higher resting anal canal pressures than the unstimulated neosphincter, and hence improved continence. However, electrostimulator failure may result in explantation in a proportion of patients. Impairment of evacuation is a functional setback in approximately one-third of patients with the gracilis neosphincter. Overall, improvement of continence may be expected in up to 90 per cent of patients according to some reports. By contrast, experience with the artificial neosphincter, which is less expensive, has been limited to a few tertiary centres across the world. Reported continence of stool is 100 per cent, and that of gas and stool 50 per cent, following implantation of the artificial sphincter. Both of the above operations have been associated with implant-related infection and impaired evacuation.<br><br>CONCLUSION: Neoanal sphincter operations are technically demanding, require a considerable learning experience and should be confined to specialist colorectal centres. Patients are likely to benefit from a plan that incorporates preoperative counselling and a selective approach.}, }
@article {pmid11120761, year = {2000}, author = {Kuklin, NA and Rott, L and Darling, J and Campbell, JJ and Franco, M and Feng, N and Müller, W and Wagner, N and Altman, J and Butcher, EC and Greenberg, HB}, title = {alpha(4)beta(7) independent pathway for CD8(+) T cell-mediated intestinal immunity to rotavirus.}, journal = {The Journal of clinical investigation}, volume = {106}, number = {12}, pages = {1541-1552}, pmid = {11120761}, issn = {0021-9738}, support = {R37 AI021362/AI/NIAID NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; 5T32AI07328-12/AI/NIAID NIH HHS/United States ; R37AI21362/AI/NIAID NIH HHS/United States ; }, mesh = {Adoptive Transfer ; Animals ; Antibodies, Monoclonal/immunology ; CD8-Positive T-Lymphocytes/*immunology/transplantation ; Chemotaxis, Leukocyte ; DNA-Binding Proteins/genetics/physiology ; Feces/virology ; Flow Cytometry ; Gene Deletion ; Immunoglobulin A/immunology ; Immunohistochemistry ; Integrins/genetics/*physiology ; Interferon-gamma/metabolism ; Intestine, Small/*immunology/*virology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Rotavirus/*immunology/physiology ; Rotavirus Infections/*immunology/virology ; Spleen/cytology/immunology ; Virus Shedding ; }, abstract = {Rotavirus (RV), which replicates exclusively in cells of the small intestine, is the most important cause of severe diarrhea in young children worldwide. Using a mouse model, we show that expression of the intestinal homing integrin alpha(4)ss(7) is not essential for CD8(+) T cells to migrate to the intestine or provide immunity to RV. Mice deficient in ss7 expression (ss7(-/-)) and unable to express alpha(4)ss(7) integrin were found to clear RV as quickly as wild-type (wt) animals. Depletion of CD8(+) T cells in ss7(-/-) animals prolonged viral shedding, and transfer of immune ss7(-/-) CD8(+) T cells into chronically infected Rag-2-deficient mice resolved RV infection as efficiently as wt CD8(+) T cells. Paradoxically, alpha(4)ss(7)(hi) memory CD8(+) T cells purified from wt mice that had been orally immunized cleared RV more efficiently than alpha(4)ss(7)(low) CD8(+) T cells. We explained this apparent contradiction by demonstrating that expression of alpha(4)ss(7) on effector CD8(+) T cells depends upon the site of initial antigen exposure: oral immunization generates RV-specific CD8(+) T cells primarily of an alpha(4)ss(7)(hi) phenotype, but subcutaneous immunization yields both alpha(4)ss(7)(hi) and alpha(4)ss(7)(low) immune CD8(+) T cells with anti-RV effector capabilities. Thus, alpha(4)ss(7) facilitates normal intestinal immune trafficking to the gut, but it is not required for effective CD8(+) T cell immunity.}, }
@article {pmid11119982, year = {2000}, author = {Matsuno, T and Inagaki, M and Oishi, M and Sadamori, H and Fujisawa, K and Endo, A and Okada, Y and Matsukawa, H and Nakao, A and Saito, S and Yagi, T and Tanaka, N}, title = {Ileocolonic complications after kidney transplantation.}, journal = {Transplantation proceedings}, volume = {32}, number = {7}, pages = {1880-1881}, doi = {10.1016/s0041-1345(00)01474-3}, pmid = {11119982}, issn = {0041-1345}, mesh = {Adult ; Aged ; Colonic Diseases/*diagnosis/therapy ; Drug Therapy, Combination ; Humans ; Ileal Diseases/*diagnosis/therapy ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation/immunology/*statistics &amp; numerical data ; Male ; Melena/diagnosis/therapy ; Middle Aged ; Postoperative Complications/*classification ; Retrospective Studies ; }, }
@article {pmid11106565, year = {2000}, author = {Tarlton, JF and Whiting, CV and Tunmore, D and Bregenholt, S and Reimann, J and Claesson, MH and Bland, PW}, title = {The role of up-regulated serine proteases and matrix metalloproteinases in the pathogenesis of a murine model of colitis.}, journal = {The American journal of pathology}, volume = {157}, number = {6}, pages = {1927-1935}, pmid = {11106565}, issn = {0002-9440}, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology/transplantation ; Cell Movement/physiology ; Colitis/enzymology/*etiology/immunology/physiopathology ; Colon/enzymology ; Disease Models, Animal ; Endopeptidases/physiology ; Enzyme Activation/physiology ; Epithelium/metabolism ; Extracellular Matrix/metabolism ; Feces/enzymology ; Intestinal Mucosa/metabolism ; Leukocytes/physiology ; Matrix Metalloproteinases/*metabolism ; Mice ; Mice, Inbred Strains ; Mice, SCID ; Serine Endopeptidases/*metabolism ; Severity of Illness Index ; Up-Regulation ; }, abstract = {Proteinases are important at several phases of physiological and pathological inflammation, mediating cellular infiltration, cytokine activation, tissue damage, remodeling, and repair. However, little is known of their role in the pathogenesis of inflammatory bowel disease. The aim of this study was to assess the role of tissue proteases in a mouse model of colitis. Proteolytic activity was analyzed, using gel and in situ zymography, in colonic tissues from severe combined immunodeficient mice with colitis induced by transfer of CD4(+) T lymphocytes. Serine proteinase levels increased in colitic tissue, with major species of 23 kd, 30 kd, and 45 kd. Co-migration and inhibition studies indicated that the 23-kd proteinase was pancreatic trypsin and that the 30-kd species was neutrophil elastase. Matrix metalloproteinase (MMP)-9 expression, and MMP-2 and MMP-9 activation, was elevated in colitic tissues. Proteinase levels followed a decreasing concentration gradient from proximal to distal colon. Proteolysis was localized to infiltrating leukocytes in diseased severe combined immunodeficient mice. Transmural inflammation was associated with serine proteinase and MMP activity in overlying epithelium and with marked subepithelial proteolytic activity. The results demonstrate a clear elevation in the levels and activation of proteases in colitis, potentially contributing to disease progression through loss of epithelial barrier function.}, }
@article {pmid11095356, year = {2000}, author = {Nyberg, SL and Sutherland, DE}, title = {Fecalith impaction of the terminal ileum in a diabetic transplant recipient.}, journal = {The American journal of gastroenterology}, volume = {95}, number = {11}, pages = {3286-3287}, doi = {10.1111/j.1572-0241.2000.03304.x}, pmid = {11095356}, issn = {0002-9270}, mesh = {Adult ; Diabetes Mellitus, Type 1/complications/*surgery ; Fecal Impaction/*complications ; Female ; Humans ; Ileal Diseases/*therapy ; Intestinal Obstruction/*etiology ; Kidney Transplantation ; Pancreas Transplantation ; }, }
@article {pmid11086793, year = {2000}, author = {Saad, GA and Taha, AM}, title = {Restoration of continence after shotgun injury to the anus.}, journal = {The Journal of trauma}, volume = {49}, number = {5}, pages = {954-957}, doi = {10.1097/00005373-200011000-00028}, pmid = {11086793}, issn = {0022-5282}, mesh = {Adolescent ; Anal Canal/*injuries ; Fecal Incontinence/*etiology/*prevention &amp; control ; Follow-Up Studies ; Humans ; Male ; Manometry ; Muscle, Skeletal/*transplantation ; Physical Examination ; Radiography ; Treatment Outcome ; Wounds, Gunshot/*complications/diagnostic imaging/*surgery ; }, }
@article {pmid11063162, year = {2000}, author = {Lång, K and Wikström, L and Danielsson, A and Tashima, K and Suhr, OB}, title = {Outcome of gastrointestinal complications after liver transplantation for familial amyloidotic polyneuropathy.}, journal = {Scandinavian journal of gastroenterology}, volume = {35}, number = {9}, pages = {985-989}, doi = {10.1080/003655200750023084}, pmid = {11063162}, issn = {0036-5521}, mesh = {Adult ; Amyloid Neuropathies/complications/genetics/*surgery ; Bacterial Infections/*epidemiology ; Female ; Follow-Up Studies ; Humans ; Intestine, Small/microbiology ; *Liver Transplantation ; Malabsorption Syndromes/*epidemiology ; Male ; Postoperative Complications/*epidemiology ; Time Factors ; }, abstract = {BACKGROUND: Gastrointestinal disturbances are important prognostic factors for mortality and morbidity after liver transplantation for familial amyloidotic polyneuropathy (FAP). However, the impact of liver transplantation on malabsorption and bacterial small-bowel contamination has not been evaluated.<br><br>METHODS: Twenty-three FAP patients were available for the study. They were examined for gastrointestinal disturbances as a part of the evaluation for liver transplantation for FAP. Bile acid malabsorption was diagnosed with the [75Se]-homocholic acid taurate (SeHCAT) test; fat malabsorption by measuring faecal fat excretion; and bacterial small-bowel contamination with the hydrogen breath test (HBT).<br><br>RESULTS: No significant improvement of malabsorption test results were noted from the pre-transplant evaluation 8 months (range, 2-20 months) before transplantation to the post-transplant evaluation performed a median of 20 months (range, 9-62 months) after the procedure. The SeHCAT test result became abnormal in two patients and normal in one, and changes in the test correlated with the time the patients were waiting for transplantation. Faecal fat excretion after transplantation correlated with duration of the disease and with fat excretion before transplantation. A significantly increased fat excretion was noted at the post-transplant evaluation. A change in HBT result was noted in only one patient, in whom the test result became normal; pre-transplant values correlated with those obtained after transplantation.<br><br>CONCLUSION: For most FAP patients no improvement in gastrointestinal function was found after transplantation. The finding underlines the importance of an early transplantation before the patients have developed gastrointestinal dysfunction.}, }
@article {pmid11058863, year = {2000}, author = {Thompson, JS and Ferguson, DC}, title = {Effect of the distal remnant on ileal adaptation.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {4}, number = {4}, pages = {430-434}, pmid = {11058863}, issn = {1091-255X}, mesh = {Adaptation, Physiological ; Analysis of Variance ; Animals ; Cell Division ; Eating ; Feces ; Ileum/anatomy &amp; histology/physiology/*surgery/transplantation ; Intestinal Mucosa/cytology/ultrastructure ; Jejunum/surgery ; Nutritional Status ; Organ Size ; Rats ; Rats, Inbred Lew ; Serum Albumin/analysis ; Transplantation, Isogeneic ; Weight Gain ; Weight Loss ; }, abstract = {The ileum has a greater adaptive capacity than the jejunum after intestinal resection, which may be, in part, related to increased exposure to luminal contents and intrinsic properties of the ileum However, the intestinal remnant might contribute to this adaptive response as well. Our aim was to determine the effect of the distal intestinal remnant on ileal adaptation when the ileum is proximal in the intestinal tract. Twenty-one Lewis rats were included in the study. One group (n = 7) served as unoperated control subjects, the second group (n = 7) underwent transposition of the jejunum and ileum, and the third group (n = 7) underwent 50% proximal resection with syngeneic transplantation of the ileum Nutritional status and structural adaptation were studied at 14 days. Animals in both the transposition and transplant groups initially lost weight but weights returned to above preoperative levels at 14 days. Food intake, stool weight, and serum albumin levels were similar in these two groups. Intestinal weight and diameter were similar in the proximal end of the ileal segment in the two study groups and were significantly increased compared to control values (0.26 +/- 0.04 and 0.31 +/- 0.02 vs. 0.10 +/- 0.0 g/cm and 8.4 +/- 0.5 and 9.1 +/- 0.8 vs. 4.9 +/- 0.3 mm; P < 0.05) Intestinal weight and diameter of the distal end of the ileal segment were greater than those values in unoperated control animals but were greatest in the ileal transplant group (0.15 +/- 0.1 and 0.24 +/- 0.03 vs. 0.07 +/- 0.01 g/cm and 5.6 +/- 1.1 and 8.7 +/- 0.6 vs. 4.3 +/- 0.2 mm; P < 0.05). Villus height and crypt depth were similar in both the proximal and distal ends of the ileal segments in the two study groups and were significantly increased compared to control values (642 +/- 75 and 720 +/- 15 vs. 411 +/- 24 proximal and 443 +/- 49 and 500 +/- 46 vs. 343 +/- 22 microm distal, P < 0.05; 223 +/- 34 and 244 +/- 33 vs. 173 +/- 20 proximal and 192 +/- 28 and 209 +/- 18 vs. 144 +/- 26 microm distal, P < 0.05). Proximal placement of the ileum by either transposition or transplantation results in structural adaptation. This occurs to a similar extent whether the distal remnant is jejunum or ileum. Thus increased exposure to luminal contents and intrinsic properties appear to be the important factors in the adaptive capability of the ileum when the ileum is the proximal portion of the intestinal tract.}, }
@article {pmid11044155, year = {2000}, author = {Baig, MK and Wexner, SD}, title = {Factors predictive of outcome after surgery for faecal incontinence.}, journal = {The British journal of surgery}, volume = {87}, number = {10}, pages = {1316-1330}, doi = {10.1046/j.1365-2168.2000.01592.x}, pmid = {11044155}, issn = {0007-1323}, mesh = {Anal Canal/injuries/innervation/surgery ; Anus Diseases/*surgery ; Colorectal Surgery/instrumentation/methods ; Fecal Incontinence/*surgery ; Female ; Humans ; Muscle, Skeletal/transplantation ; Obstetric Labor Complications/surgery ; Pelvic Floor ; Pregnancy ; Treatment Outcome ; }, abstract = {BACKGROUND: Surgical treatment of faecal incontinence may be categorized into procedures that either repair or augment the native sphincter mechanism or, alternatively, require construction of a neosphincter using either autologous tissue or an artificial device.<br><br>METHODS: This article reviews the currently available surgical options for the treatment of faecal incontinence, discusses factors predictive of outcome, and includes an algorithm for treatment.<br><br>RESULTS AND CONCLUSION: Procedures such as postanal repair, direct sphincter repair and reefing are seldom used. Overlapping repair has become the operation of choice in incontinent patients with isolated anterior defects in the external anal sphincter muscle, particularly in postobstetric trauma. Pudendal neuropathy seems to be a predictive factor of success, although this is not universally accepted. Total pelvic floor repair has been offered as a recent alternative. Neosphincter procedures include a gluteoplasty, non-stimulated and stimulated unilateral or bilateral graciloplasty and artificial bowel sphincter. The success and morbidity rates with the stimulated graciloplasty and artificial bowel sphincter appear similar. The newest alternative, sacral nerve stimulation, seems promising. In the final analysis, case selection and surgical judgement are probably the most important factors influencing the success of surgery for faecal incontinence. Presented as the Edinburgh Royal College of Surgeons invited lecture to the Association of Coloproctology of Great Britain and Ireland, Southport, UK, June 1999}, }
@article {pmid11040945, year = {2000}, author = {Woo, PC and Leung, PK and Leung, KW and Yuen, KY}, title = {Identification by 16S ribosomal RNA gene sequencing of an Enterobacteriaceae species from a bone marrow transplant recipient.}, journal = {Molecular pathology : MP}, volume = {53}, number = {4}, pages = {211-215}, pmid = {11040945}, issn = {1366-8714}, mesh = {Adult ; *Bacterial Typing Techniques ; Base Sequence ; *Bone Marrow Transplantation ; Diarrhea/immunology/microbiology ; Enterobacteriaceae/*classification/genetics/isolation &amp; purification ; Enterobacteriaceae Infections/*diagnosis/immunology ; Feces/microbiology ; Female ; Humans ; Immunocompromised Host ; Molecular Sequence Data ; Polymerase Chain Reaction ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {AIMS: To ascertain the clinical relevance of a strain of Enterobacteriaceae isolated from the stool of a bone marrow transplant recipient with diarrhoea. The isolate could not be identified to the genus level by conventional phenotypic methods and required 16S ribosomal RNA (rRNA) gene sequencing for full identification.<br><br>METHODS: The isolate was investigated phenotypically by standard biochemical methods using conventional biochemical tests and two commercially available systems, the Vitek (GNI+) and API (20E) systems. Genotypically, the 16S bacterial rRNA gene was amplified by the polymerase chain reaction (PCR) and sequenced. The sequence of the PCR product was compared with known 16S rRNA gene sequences in the GenBank database by multiple sequence alignment.<br><br>RESULTS: Conventional biochemical tests did not reveal a pattern resembling any known member of the Enterobacteriaceae family. The isolate was identified as Salmonella arizonae (73%) and Escherichia coli (76%) by the Vitek (GNI+) and API (20E) systems, respectively. 16S rRNA sequencing showed that there was only one base difference between the isolate and E coli K-12, but 48 and 47 base differences between the isolate and S typhimurium (NCTC 8391) and S typhi (St111), respectively, showing that it was an E coli strain. The patient did not require any specific treatment and the diarrhoea subsided spontaneously.<br><br>CONCLUSIONS: 16S rRNA gene sequencing was useful in ascertaining the clinical relevance of the strain of Enterobacteriaceae isolated from the stool of the bone marrow transplant recipient with diarrhoea.}, }
@article {pmid11030872, year = {2000}, author = {Bouamrirène, D and Micallef, JP and Rouanet, P and Bacou, F}, title = {Electrical stimulation-induced changes in double-wrapped muscles for dynamic graciloplasty.}, journal = {Archives of surgery (Chicago, Ill. : 1960)}, volume = {135}, number = {10}, pages = {1161-1167}, doi = {10.1001/archsurg.135.10.1161}, pmid = {11030872}, issn = {0004-0010}, mesh = {Animals ; Disease Models, Animal ; Electric Stimulation ; Fecal Incontinence/*surgery ; Female ; Fructose-Bisphosphate Aldolase/*metabolism ; Immunohistochemistry ; Muscle Contraction/physiology ; Muscle Fibers, Skeletal/*enzymology/pathology ; Muscle, Skeletal/pathology/*physiopathology/transplantation ; Myosin Heavy Chains/*analysis ; Probability ; Rabbits ; Reference Values ; Sensitivity and Specificity ; Statistics, Nonparametric ; }, abstract = {HYPOTHESIS: Treatment of fecal incontinence has been greatly improved by electrical stimulation of gracilis muscle transposed around the anal canal. Various configurations of the muscle have been used: single alpha, gamma, epsilon muscle loops, split sling, or double wrap. We report herein experimental data on muscle transformation and damage induced by the latter surgical approach.<br><br>This study was conducted on 4 groups of New Zealand white rabbits. Group 1 had unstimulated transposed gracilis muscles. Group 2 had left transposed gracilis muscles stimulated only. Group 3 had both right and left transposed gracilis muscles stimulated. Group 4 were the controls (not operated on). Muscle properties were studied by electrophysiological,immunohistochemical,and biochemical techniques.<br><br>RESULTS: Transformation from fast-contractile glycolytic muscle fibers into fast-intermediate to slow-contractile oxidative muscle fiber types induced a fatigue resistance of the transposed muscle that has undergone long-term stimulation and muscle alterations characterized by fiber atrophy and fibrosis.<br><br>CONCLUSIONS: Whatever technique of dynamic graciloplasty is used, muscle degeneration associated with mobilization might result primarily from the surgical dissection, whereby collateral blood supply to the gracilis is interrupted and exacerbated by long-term stimulation.}, }
@article {pmid11029139, year = {2000}, author = {Rogers, M and Weinstock, DM and Eagan, J and Kiehn, T and Armstrong, D and Sepkowitz, KA}, title = {Rotavirus outbreak on a pediatric oncology floor: possible association with toys.}, journal = {American journal of infection control}, volume = {28}, number = {5}, pages = {378-380}, doi = {10.1067/mic.2000.109908}, pmid = {11029139}, issn = {0196-6553}, mesh = {Cancer Care Facilities ; Child ; Cross Infection/*epidemiology/transmission ; *Disease Outbreaks ; Feces/virology ; Female ; Gastroenteritis/*epidemiology/virology ; Humans ; Infant ; Infection Control ; Intensive Care Units, Pediatric ; Male ; New York City/epidemiology ; *Play and Playthings ; Rotavirus Infections/*epidemiology/transmission ; }, abstract = {BACKGROUND: Several outbreaks of rotavirus gastroenteritis have occurred in hospitals and day care centers. In the spring of 1997, an outbreak of rotavirus occurred on our pediatric unit. Aggressive infection control measures were instituted, and potential lapses in infection control were assessed.<br><br>METHODS: Memorial Sloan-Kettering Cancer Center is a 434-bed cancer hospital in New York City. The pediatric unit is a 42-bed ward with both bone marrow transplant patients and non-bone marrow transplant oncology patients. Nosocomially acquired rotavirus was defined as diarrhea, vomiting, or gastrointestinal upset with onset 48 hours or more after hospital admission, accompanied by a positive enzyme immunoassay for rotavirus antigen.<br><br>RESULTS: Between February 24 and April 4, 1997, 8 patients on the pediatric unit had nosocomial rotavirus. Aggressive infection control measures were instituted. Patients with rotavirus were cohorted and placed on contact precautions (strict handwashing, gloves, and gown). Investigation by the infection control team revealed that communal toys in the playroom were not being cleaned according to the weekly protocol.<br><br>CONCLUSIONS: An outbreak of nosocomial rotavirus occurred on our pediatric oncology unit. Shared toys may have served as fomites in the transmission of rotavirus.}, }
@article {pmid11007826, year = {2000}, author = {Kim, YO and Yang, CW and Yoon, SA and Song, HC and Kim, YS and Kim, SY and Choi, EJ and Chang, YS and Bang, BK}, title = {Intestinal protein loss in patients with haemorrhagic fever with renal syndrome.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {15}, number = {10}, pages = {1588-1592}, doi = {10.1093/ndt/15.10.1588}, pmid = {11007826}, issn = {0931-0509}, mesh = {Adult ; Feces/chemistry ; Female ; Hemorrhagic Fever with Renal Syndrome/diagnostic imaging/*metabolism ; Humans ; Intestinal Mucosa/*metabolism ; Male ; Middle Aged ; Radionuclide Imaging ; Radiopharmaceuticals ; Reference Values ; Serum Albumin/*metabolism ; Technetium Tc 99m Aggregated Albumin ; alpha 1-Antitrypsin/analysis ; }, abstract = {BACKGROUND: In haemorrhagic fever with renal syndrome (HFRS) vascular dysfunction has been observed in various organs, but the involvement of the intestine has not yet been reported. This study was performed to evaluate the association of intestinal protein loss in this disease with other clinical parameters reflecting vascular permeability or disease severity.<br><br>METHODS: Twenty patients with HFRS were included in this study. Intestinal protein loss was measured by (99m)Tc-human serum albumin ((99m)Tc-HSA) scintigraphy in the acute stage, and quantitative analysis of protein loss was measured by the faecal clearance of alpha 1-antitrypsin (C(AT)) in the acute and the recovery stages. C(AT) was then compared with clinical parameters reflecting disease activity and vascular permeability.<br><br>RESULTS: (99m)Tc-HSA scintigraphy was positive in 13 (65%) patients, and C(AT) in the acute stage was significantly increased as compared with C(AT) in the recovery stage (40.5+/-24.1 vs 9.2+/-4.2 ml/day, P<0.001). C(AT) was associated with serum albumin levels, frequency of hypotensive episodes, severity of acute renal failure, and degree of thrombocytopenia.<br><br>CONCLUSIONS: Our data suggest that the increased vascular permeability of HFRS is associated with the increased intestinal loss of plasma proteins, which might represent one of the parameters of disease severity in HFRS.}, }
@article {pmid11003351, year = {2000}, author = {Kissler, HJ and Gepp, H and Schwille, PO}, title = {Metabolic consequences of orthotopic pancreaticoduodenal transplantation with preservation of near normal physiology.}, journal = {Transplantation}, volume = {70}, number = {5}, pages = {747-754}, doi = {10.1097/00007890-200009150-00006}, pmid = {11003351}, issn = {0041-1337}, mesh = {Animals ; Body Weight ; Duodenum/*transplantation ; Glucose Tolerance Test ; Immune Tolerance/physiology ; Insulin/analysis/blood ; Islets of Langerhans/chemistry/physiology ; Male ; Models, Biological ; Neurotransmitter Agents/analysis ; Pancreas/chemistry ; Pancreas Transplantation/*physiology ; Rats ; Rats, Inbred Lew ; Rats, Wistar ; }, abstract = {BACKGROUND: Several case reports suggested the use of pancreaticoduodenal allotransplantation alone or in combination with multivisceral transplants to treat exocrine and endocrine deficiency after pancreatectomy for chronic pancreatitis, upper abdominal malignancies, and cystic fibrosis. Our objective was to establish the metabolic consequences of this technique.<br><br>METHODS: Inbred rats, which either underwent pancreaticoduodenectomy before receiving an orthotopic duodenopancreas transplant (Tx, n= 18) or laparotomy (sham, n=18), were subjected 3 months postoperatively to oral and "isoglycemic" i.v. glucose tolerance tests with arterial blood sampling (n=12) or oral glucose tolerance test with additional portal blood sampling (n=6). Fecal fat and chymotrypsin were evaluated in the 11th postoperative week as indicators of pancreatic exocrine function in eight animals of each group.<br><br>RESULTS: The incremental arterial plasma glucose integrated over a 90-min period was similar after oral and i.v. glucose in the respective groups, but was significantly lower in Tx versus sham rats after oral glucose. Incremental portal glucose was also lower after oral glucose, while hepatic glucose extraction remained unchanged. The incremental response of arterial glucose-dependent insulinotropic peptide, and of arterial and portal insulin, was comparable in Tx and sham rats; also in both groups the arterial response was significantly greater with oral versus i.v. glucose, and the incretin effect for insulin was intact after transplantation. Fecal fat and chymotrypsin levels did not differ between the two groups.<br><br>CONCLUSIONS: 1) In the Tx rat lower incremental plasma glucose after oral glucose intake likely results from decreased intestinal glucose uptake; 2) preservation of a normal entero-insular axis of insulin together with the absence of intestinal malabsorption of lipids suggest that orthotopic transplantation of a duodeno-pancreas preserved endocrine and exocrine pancreatic function and therefore qualifies as treatment modality for the above named indications.}, }
@article {pmid10987532, year = {2000}, author = {Zonnevijlle, ED and Somia, NN and Abadia, GP and Stremel, RW and Maldonado, CJ and Werker, PM and Kon, M and Barker, JH}, title = {Sequential segmental neuromuscular stimulation reduces fatigue and improves perfusion in dynamic graciloplasty.}, journal = {Annals of plastic surgery}, volume = {45}, number = {3}, pages = {292-297}, doi = {10.1097/00000637-200045030-00012}, pmid = {10987532}, issn = {0148-7043}, mesh = {Animals ; Dogs ; Electric Stimulation ; *Muscle Fatigue ; Muscle, Skeletal/blood supply/*physiology/*transplantation ; *Neuromuscular Junction ; Pressure ; Regional Blood Flow ; }, abstract = {Dynamic graciloplasty is used as a treatment modality for total urinary incontinence caused by a paralyzed sphincter. A problem with this application is undesirable fatigue of the muscle caused by continuous electrical stimulation. Therefore, the neosphincter must be trained via a rigorous regimen to transform it from a fatigue-prone state to a fatigue-resistant state. To avoid or shorten this training period, the application of sequential segmental neuromuscular stimulation (SSNS) was examined. This form of stimulation proved previously to be highly effective in acutely reducing fatigue caused by electrical stimulation. The contractile function and perfusion of gracilis muscles employed as neosphincters were compared between conventional, single-channel, continuous stimulation, and multichannel sequential stimulation in 8 dogs. The sequentially stimulated neosphincter proved to have an endurance 2.9 times longer (as measured by halftime to fatigue) than continuous stimulation and a better blood perfusion during stimulation (both of which were significant changes, p < 0.05). Clinically, this will not antiquate training of the muscle, but SSNS could reduce the need for long and rigorous training protocols, making dynamic graciloplasty more attractive as a method of treating urinary or fecal incontinence.}, }
@article {pmid10967569, year = {2000}, author = {van Kraaij, MG and Dekker, AW and Verdonck, LF and van Loon, AM and Vinjé, J and Koopmans, MP and Rozenberg-Arska, M}, title = {Infectious gastro-enteritis: an uncommon cause of diarrhoea in adult allogeneic and autologous stem cell transplant recipients.}, journal = {Bone marrow transplantation}, volume = {26}, number = {3}, pages = {299-303}, pmid = {10967569}, issn = {0268-3369}, mesh = {Adult ; Clostridioides difficile ; Diarrhea/*etiology/microbiology ; Enterocolitis, Pseudomembranous/complications/etiology/microbiology ; Feces/microbiology ; Female ; Gastroenteritis/*complications/etiology/microbiology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Prospective Studies ; }, abstract = {The incidence and aetiology of acute diarrhoea in 60 adult allogeneic or autologous stem cell transplant (SCT) recipients was determined in a prospective study. Stool specimens were obtained prior to SCT and on days +20, +40, +60 and +100 post transplant. Microbiological evaluation was performed for pathogenic bacteria, fungi, parasites and viruses. Forty-seven patients were evaluable of whom 31 had a total of 48 acute diarrhoeal episodes. Diarrhoea occurred in 79% of allogeneic and 47% of autologous SCT recipients (P < 0.05). Intestinal infections were found in three of 48 (6%) diarrhoeal episodes. Clostridium difficile with positive toxin was cultured twice and one stool specimen was positive for cryptosporidium. Intestinal pathogens were identified in 13 out of 172 stool specimens from asymptomatic patients and included: rotavirus (4), adenovirus (3), C. difficile, toxin positive (2), and others (4). Graft-versus-host disease was confirmed by biopsy in two of 36 episodes of diarrhoea in allogeneic patients, and in three patients a relationship between reactivation of cytomegalovirus and diarrhoea was suspected. In 40 of 48 (83%) episodes of diarrhoea no clear aetiology could be found.}, }
@article {pmid10964540, year = {2000}, author = {Brimnes, J and Reimann, J and Claesson, MH}, title = {Immunoglobulin leakiness in scid mice with CD4(+) T-cell-induced chronic colitis.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {96}, number = {3}, pages = {222-229}, doi = {10.1006/clim.2000.4891}, pmid = {10964540}, issn = {1521-6616}, mesh = {Animals ; CD4-Positive T-Lymphocytes/physiology/transplantation ; Colitis/*etiology/*immunology/metabolism ; Colon/cytology/immunology ; Feces/*chemistry ; Immunoglobulin Isotypes/metabolism ; Immunoglobulins/*analysis ; Lymph Nodes/immunology ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Spleen/chemistry/cytology/immunology ; alpha 1-Antitrypsin/metabolism ; }, abstract = {Inflammatory bowel disease in scid mice is initiated by transplantation of CD4(+) T-cells from immunocompetent syngenic donor mice. As the disease progresses, immunoglobulin (Ig)-containing cells appear in the gut lamina propria, suggesting that locally accumulating Ig may play a role in disease development. In the present work we have investigated the relationship between disease progression and patterns or levels of Ig isotypes in the feces of scid mice suffering from an ongoing colitis. The data clearly showed that the severity or progression of the disease did not influence the levels of IgA, IgG1, IgG2a, IgG2b, and IgG3, whereas the level of fecal IgM increased during the course of colitis. The presence of the serum protein alpha-1-antitrypsin in fecal extracts from diseased mice suggests that some of the fecal Ig has leaked through the inflamed epithelial membrane into the gut lumen. Finally, Ig-containing cells were observed in mesenteric lymph nodes and in the spleen, suggesting that the fecal Ig is produced both systemically and locally in the gut wall. In conclusion, the present results demonstrate that the level of IgM increases as colitis progresses. Also, the five remaining major Ig isotypes are increased in the gut lumen of scid mice with colitis, but the individual Ig types vary randomly during the course of the disease. Thus, it is unlikely that immunoglobulins are involved in the immunopathogenesis of this model of colitis.}, }
@article {pmid10951792, year = {1998}, author = {Barisić, G and Krivokapić, Z and Marsavelska, A and Popović, M and Saranović, D}, title = {[Dynamic graciloplasty in the treatment of severe fecal incontinence--2 case reports].}, journal = {Acta chirurgica Iugoslavica}, volume = {45}, number = {2 Suppl}, pages = {73-77}, pmid = {10951792}, issn = {0354-950X}, mesh = {Adult ; Anal Canal/*surgery ; Electric Stimulation Therapy ; Fecal Incontinence/*surgery ; Humans ; Male ; Muscle, Skeletal/*transplantation ; }, abstract = {Severe fecal incontinence is a serious problem not only for the patient whose quality of life is diminished, but also for the surgeon, who sometimes has difficulties how to manage all the aspects of this complicated condition. Conservative treatment is often ineffective, while operative sphincter repair is feasible only when anal sphincter is relatively functional and conserved. Dynamic graciloplasty is a method where functional anal neosphincter is constructed by transposing m. gracilis and wrapping it around the anal canal with subsequent implantation of electric neurostimulator and electrodes. Relatively good continence can be achieved with this technique, especially in-patients where all other therapeutic options failed. We present two patients, 25 and 21 years old, operated on our department, both suffered from severe fecal incontinence from the time they were born. They were interviewed, underwent a physical examination and evaluated by anal manometry, defecography and electromyography. Severe fecal incontinence was revealed (18 and 20, according to the Continence grading scale). In both cases, Gamma graciloplasty was performed. At first patient, implantation of the neurostimulator was performed 8 months after graciloplasty, while in second case, both graciloplasty and implantation of the electrodes with neurostimulator were performed at the same time. Postoperative recovery was uneventful in both cases. There was minor infection of the perineal wound in one patient. Electrostimulation training program was started on 9th postoperative day in both cases. Functional results were revealed by questionnaire and anal manometry. The quality of life was significantly improved in both cases, with good continence and psychological recovery. Anal manometry revealed increased anal contraction pressure comparing with preoperative basal and squeeze pressures. Dynamic graciloplasty is a relatively new; high specialized method in treatment of intractable, fecal incontinence. It is safe and reliable procedure in hands of an well-experienced surgeon, if well indicated and performed.}, }
@article {pmid10897048, year = {2000}, author = {Rutgers, M and Buitenhuis, CK and Hoefnagel, CA and Voûte, PA and Smets, LA}, title = {Targeting of meta-iodobenzylguanidine to SK-N-SH human neuroblastoma xenografts: tissue distribution, metabolism and therapeutic efficacy.}, journal = {International journal of cancer}, volume = {87}, number = {3}, pages = {412-422}, doi = {10.1002/1097-0215(20000801)87:3&lt;412::aid-ijc16&gt;3.0.co;2-x}, pmid = {10897048}, issn = {0020-7136}, mesh = {3-Iodobenzylguanidine/administration &amp; dosage/*pharmacokinetics/therapeutic use/toxicity ; Animals ; Biotransformation ; Dose Fractionation, Radiation ; Drug Administration Schedule ; Humans ; Iodine Radioisotopes/administration &amp; dosage/*pharmacokinetics/therapeutic use/toxicity ; Mice ; Mice, Inbred C3H ; Mice, Nude ; Neoplasm Transplantation ; Neuroblastoma/diagnostic imaging/metabolism/pathology/*radiotherapy ; Radioisotope Teletherapy ; Radiometry/methods ; Radionuclide Imaging ; Radiopharmaceuticals/*pharmacokinetics/therapeutic use/toxicity ; Species Specificity ; Tissue Distribution ; Transplantation, Heterologous ; Tumor Cells, Cultured/transplantation ; }, abstract = {The clinical results of [(131)I]meta-iodobenzylguanidine (MIBG)-targeted radiotherapy in neuroblastoma patients is highly variable. To assess the therapeutic potential of [(131)I]MIBG, we used the SK-N-SH human neuroblastoma, xenografted in nude mice. The model was first characterized for basic parameters of MIBG handling in the host species. This demonstrated the presence of both strain- and nu/nu mutation-related differences in [(131)I]MIBG biodistribution. Fecal and urinary clearance rates of [(131)I]MIBG in mice roughly resemble those in humans, but mice metabolize MIBG more extensively. In both species, enzymatic deiodination in vivo was not an important metabolic route. Therapy with increasing [(131)I]MIBG doses (25-92 MBq) given as single i.v. injections resulted in proportionally increasing specific growth delay values (tumor regrowth delay/doubling time) of 1 to 5. Using gamma-camera scintigraphy for non-invasive dosimetry, the corresponding calculated absorbed tumor radiation doses ranged from 2 to 11 Gy. We also compared the therapeutic effects of a single [(131)I]MIBG administration with those resulting from a more protracted exposure by fractionating the dose in 2 to 6 injections or with high dose rate external-beam irradiation. No therapeutic advantage of a fractionated schedule was observed, and 5.5 Gy delivered by low dose-rate [(131)I]MIBG endo-irradiation was equi-effective with 5.0 Gy X-rays. The SK-N-SH neuroblastoma xenograft model thus appears suitable to evaluate possible treatment improvements to reach full potential of MIBG radiotherapy.}, }
@article {pmid10885489, year = {2000}, author = {Kissler, HJ and Hofmann, G and Gepp, H and Erben, RG and Schwille, PO}, title = {High insulin and low IGF-I plasma levels following pancreas transplantation in rats. Implications for bone and mineral metabolism.}, journal = {Scandinavian journal of clinical and laboratory investigation}, volume = {60}, number = {3}, pages = {175-187}, doi = {10.1080/003655100750044820}, pmid = {10885489}, issn = {0036-5513}, mesh = {Animals ; Bone and Bones/anatomy &amp; histology/chemistry/*metabolism ; Calcium/metabolism/urine ; Feces ; Glucose/administration &amp; dosage ; Hyperinsulinism/metabolism ; Insulin/*blood ; Insulin-Like Growth Factor I/analysis ; Intestinal Absorption ; Islets of Langerhans/physiology ; Magnesium/metabolism/urine ; Male ; Minerals/*metabolism ; *Pancreas Transplantation ; Phosphorus/metabolism/urine ; Rats ; Rats, Inbred Strains ; }, abstract = {Primary disturbances in mineral metabolism and deficiencies in insulin and insulin-like growth factor-I (IGF-I) have been implicated in the pathogenesis of diabetic osteopenia. This prompted us to investigate whether normal bone minerals and bone morphology are preserved after pancreas transplantation. To this end, 8 inbred rats (transplants) were compared with 9 sham-operated rats (controls) 20 months after orthotopic pancreas transplantation. While basal levels of insulin remained unaffected by transplantation, an oral glucose load elicited hyperinsulinemia (integrated incremental response: mean +/- SEM, 62+/-8 nmol l(-1) 60 min in transplants vs. 32+/-6 nmol l(-1) 60 min in controls; p<0.01) in the presence of normal glucose levels. Fecal and urinary excretion and fractional intestinal absorption of calcium, magnesium and phosphorus, net calcium absorption and the respective serum mineral levels were unchanged after transplantation, as were those of the calciotropic hormones. Serum osteocalcin and bone alkaline phosphatase remained unaffected, and urinary excretion of pyridinium and deoxypyridinium were unchanged. Fasting plasma IGF-I concentration was significantly decreased in transplants (930+/-42 ng ml(-1)) vs. control rats (1074+/-49 ng ml(-1); p < 0.05). Despite similar physical and chemical properties of bone in both groups, histomorphometry revealed slight osteopenia in transplant rats, as reflected by a 38% reduction in the cancellous bone area of the proximal tibial metaphysis. Plasma IGF-I levels were significantly correlated with bone mineral apposition rate (r=0.70, p<0.02), osteoblast perimeter (r=0.60, p<0.05) and osteoid perimeter (r=0.60, p<0.05). In conclusion, pancreas transplantation preserves physical and chemical properties of bone, but bone metabolism is not completely normal after transplantation, as evidenced by decreased cancellous bone. This might have resulted from the insulin resistance associated with the lowering of the plasma IGF-I level, which was correlated with the mineral apposition rate.}, }
@article {pmid10869291, year = {2000}, author = {Fontanellas, A and Mazurier, F and Landry, M and Taine, L and Morel, C and Larou, M and Daniel, JY and Montagutelli, X and de Salamanca, RE and de Verneuil, H}, title = {Reversion of hepatobiliary alterations By bone marrow transplantation in a murine model of erythropoietic protoporphyria.}, journal = {Hepatology (Baltimore, Md.)}, volume = {32}, number = {1}, pages = {73-81}, doi = {10.1053/jhep.2000.8531}, pmid = {10869291}, issn = {0270-9139}, mesh = {Animals ; *Bone Marrow Transplantation ; Female ; Liver/metabolism/*pathology ; Male ; Mice ; Mice, Inbred BALB C ; Porphyria, Erythropoietic/metabolism/pathology/*therapy ; Protoporphyrins/biosynthesis ; }, abstract = {Erythropoietic protoporphyria (EPP) is characterized clinically by cutaneous photosensitivity and biochemically by the accumulation of excessive amounts of protoporphyrin in erythrocytes, plasma, feces, and other tissues, such as the liver. The condition is inherited as an autosomal dominant or recessive trait, with a deficiency of ferrochelatase activity. A major concern in EPP patients is the development of cholestasis with accumulation of protoporphyrin in hepatobiliary structures and progressive cellular damage, which can rapidly lead to fatal hepatic failure. The availability of a mouse model for the disease, the Fech(m1Pas)/Fech(m1Pas) mutant mouse, allowed us to test a cellular therapy protocol to correct the porphyric phenotype. When Fech/Fech mice received bone marrow cells from normal animals, the accumulation of protoporphyrin in red blood cells and plasma was reduced 10-fold but still remained 2.5 times above normal levels. Interestingly, in very young animals, bone marrow transplantation can prevent hepatobiliary complications as well as hepatocyte alterations and partially reverse protoporphyrin accumulation in the liver. Bone marrow transplantation may be an option for EPP patients who are at risk of developing hepatic complications.}, }
@article {pmid10835843, year = {2000}, author = {Ashida, T and Tsubaki, K and Hasegawa, H and Kanamaru, A}, title = {A comparative study of changes in fecal flora in patients preconditioned with either amphotericin B or fluconazole for allogeneic bone marrow transplantation.}, journal = {Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases}, volume = {74}, number = {4}, pages = {365-371}, doi = {10.11150/kansenshogakuzasshi1970.74.365}, pmid = {10835843}, issn = {0387-5911}, mesh = {Adolescent ; Adult ; Amphotericin B/administration &amp; dosage/*pharmacology ; Anti-Bacterial Agents/administration &amp; dosage ; Antifungal Agents/administration &amp; dosage/*pharmacology ; *Bone Marrow Transplantation ; Feces/microbiology ; Fluconazole/administration &amp; dosage/*pharmacology ; Humans ; Middle Aged ; Tobramycin/administration &amp; dosage ; Transplantation Conditioning/*methods ; Transplantation, Homologous ; Vancomycin/administration &amp; dosage ; }, abstract = {The present study investigated fecal flora changes in 20 patients who received either the nonabsorbable antifungal agent amphotericin B, or the absorbable antifungal agent fluconazole, with tobramycin and vancomycin as preparation for undergoing allogeneic bone marrow transplantation (BMT). The oral antibiotic regimen consisted of tobramycin (540 mg/day, three times a day), vancomycin (1,500 mg/day, three times a day) and either amphotericin B (2,400 mg/day, twice a day) (AMPH group) or fluconazole (400 mg/day, twice a day) (FLCZ group) and was designed to prevent infections from microorganisms in the gut. Aerobic bacterial colonies were not detected on the day of BMT or 1 week after BMT, except in 1 case unable to take the full antibiotic regimen due to nausea and vomiting. Anaerobic bacterial colonies were not detected on the day of BMT except in this single case. Furthermore, there were no episodes of bacterial infection. In both groups, Candida colonies were detected in some case. Candida colonies were also detected in the pharynx and urine. However, there were no fungal infections. The present report suggests that amphotericin B and fluconazole administrations, with tobramycin and vancomycin, are equally effective for protection against bacterial and fungal infections in BMT recipients.}, }
@article {pmid10808209, year = {2000}, author = {Knowles, S and Herra, C and Devitt, E and O'Brien, A and Mulvihill, E and McCann, SR and Browne, P and Kennedy, MJ and Keane, CT}, title = {An outbreak of multiply resistant Serratia marcescens: the importance of persistent carriage.}, journal = {Bone marrow transplantation}, volume = {25}, number = {8}, pages = {873-877}, doi = {10.1038/sj.bmt.1702218}, pmid = {10808209}, issn = {0268-3369}, mesh = {Adult ; Aged ; Carrier State/transmission ; Cross Infection ; *Disease Outbreaks ; Disease Reservoirs ; *Drug Resistance, Multiple ; Equipment Contamination ; Feces/microbiology ; Female ; Hospital Units ; Humans ; Male ; Middle Aged ; Neutropenia/complications ; Sanitation ; Serotyping ; *Serratia Infections/drug therapy/etiology/transmission ; *Serratia marcescens ; Time Factors ; }, abstract = {An outbreak of multi-resistant Serratia marcescens involving 24 patients occurred in a bone marrow transplant and oncology unit, from September 1998 to June 1999, of whom 14 developed serious infection. This is the first such outbreak described in a BMT unit. All isolates demonstrated the same antimicrobial susceptibility pattern and were the same unusual serotype O21:K14. The antimicrobial susceptibility profile showed reduced susceptibility to ciprofloxacin, gentamicin and piperacillin-tazobactam. As the latter two antimicrobials are part of our empiric therapy for febrile neutropenia, they were substituted with meropenem and amikacin during the outbreak. Investigation revealed breaches in infection control practices. Subsequently, the outbreak was contained following implementation of strict infection control measures. A prominent feature of the outbreak was prolonged carriage in some patients. These patients may have acted as reservoirs for cross-infection. This report also indicates that patients who become colonised with Serratia marcescens may subsequently develop invasive infection during neutropenic periods.}, }
@article {pmid10795597, year = {2000}, author = {Metge, S and Van Nhieu, JT and Dahmane, D and Grimbert, P and Foulet, F and Sarfati, C and Bretagne, S}, title = {A case of Enterocytozoon bieneusi infection in an HIV-negative renal transplant recipient.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {19}, number = {3}, pages = {221-223}, doi = {10.1007/s100960050463}, pmid = {10795597}, issn = {0934-9723}, mesh = {Adult ; Animals ; Diarrhea/parasitology ; Feces/parasitology ; Female ; *HIV Seronegativity ; Humans ; *Kidney Transplantation ; Microsporida/*isolation &amp; purification ; Microsporidiosis/*diagnosis/parasitology ; }, abstract = {Reported here is a case of microsporidiosis that occurred in an HIV-negative renal transplant recipient. The patient developed protracted diarrhea 18 months following transplant surgery. Many spores of Enterocytozoon bieneusi were detected in stool smears using a modified trichrome staining method. Identification was confirmed using the polymerase chain reaction. Histological examination of duodenal biopsies revealed numerous spores in the cytoplasm of enterocytes. Tacrolimus and steroid regimens were decreased, treatment with mycophenolate mofetil was discontinued, and the patient was given albendazole and metronidazole for 2 weeks. The diarrhea resolved after 15 days of treatment; 2 months later the patient had recovered completely. A more systematic search for microsporidia using specific staining procedures should be performed in transplant recipients who develop severe diarrhea.}, }
@article {pmid10706041, year = {2000}, author = {Wolff, C and Diekmann, A and Boomgaarden, M and Körner, MM and Kleesiek, K}, title = {Viremia and excretion of TT virus in immunosuppressed heart transplant recipients and in immunocompetent individuals.}, journal = {Transplantation}, volume = {69}, number = {3}, pages = {351-356}, doi = {10.1097/00007890-200002150-00007}, pmid = {10706041}, issn = {0041-1337}, mesh = {Adolescent ; Adult ; Aged ; Base Sequence ; Carrier State ; DNA Viruses/genetics/*isolation &amp; purification ; DNA, Viral/analysis ; Female ; Heart Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Polymerase Chain Reaction ; Tissue Donors ; Viremia/*etiology/virology ; }, abstract = {BACKGROUND: The TT virus (TTV) was discovered in patients with symptomatic posttransfusion hepatitis, but many viremic individuals are asymptomatic. Inadvertent transfusion-associated transmission must therefore be anticipated. We screened blood donors and heart transplant recipients for TTV infections.<br><br>METHODS: Nested polymerase chain reaction was used to detect TTV DNA in plasma, serum, urine, and fecal samples from 600 blood donors, from 100 healthy individuals, and from 495 heart transplant recipients.<br><br>RESULTS: A total of 3.2% of the blood donors, but 25% of the heart transplant recipients were viremic. TTV subtypes G1a/b and G2a/b were observed in both groups, but the subtype distributions were discrepant. A severe, acute infection with TTV subtype 3 was observed in one blood donor. The prevalence of TTV infections in heart transplant recipients was not correlated to transfusion frequency. Nine viremic heart transplant recipients and their 75 blood donors were studied in detail. Seven blood donors were viremic, but only two "pairs" of viremic blood donors and transfusion recipients had identical TTV isolates. TTV DNA was detected in the feces of 5% (5/100) of immunocompetent individuals (staff), in 46% (52/112) of viremic heart transplant recipients, and in the urine of 55% (20/36). TTV DNA was detected in six of six batches of pooled "virus-inactivated" plasma (solvent/detergent treated), and in none of eight batches of commercial immunoglobulins.<br><br>CONCLUSION: Although TTV is transfusion-transmissible, the parenteral transmission rate may have been overestimated. Many TTV infections are apparently acquired by nonparenteral routes. Immunoglobulins are safe but pooled plasma is not safe regarding TTV transmission.}, }
@article {pmid10697165, year = {2000}, author = {Bardoel, JW and Stadelmann, WK and Tobin, GR and Werker, PM and Stremel, RW and Kon, M and Barker, JH}, title = {Use of the rectus abdominis muscle for abdominal stoma sphincter construction: an anatomical feasibility study.}, journal = {Plastic and reconstructive surgery}, volume = {105}, number = {2}, pages = {589-595}, doi = {10.1097/00006534-200002000-00017}, pmid = {10697165}, issn = {0032-1052}, mesh = {Abdomen/*surgery ; Cadaver ; Feasibility Studies ; Humans ; Rectus Abdominis/*transplantation ; *Surgical Flaps/innervation ; *Surgical Stomas ; }, abstract = {Permanent fecal abdominal stomas significantly decrease quality of life. Previous attempts to create continent stomas by using dynamic myoplasty procedures have resulted in disappointing outcomes, primarily owing to denervation atrophy of the muscle flap that was used in the creation of the sphincter and because of muscle fatigue resulting from continuous electrical stimulation that is received by the flap to force contraction. On the basis of these problems, we designed two separate studies: an anatomical study addressing flap denervation and a functional study addressing muscle fatigue. The present study addresses the first topic and was designed to develop a rectus abdominis muscle flap into a sphincter that was anatomically situated to create a stoma while preserving as much innervation as possible. In 24 rectus abdominis muscles of human cadavers, the neurovascular anatomy was defined, then the anatomical feasibility of two different muscle flap configurations was considered. The flaps investigated were the peninsula flap and island flap designs, with both using the most caudal segment of the rectus abdominis muscle in construction of the sphincter. Neither flap design required the killing of a nerve for stoma sphincter creation, resulting in minimal muscle denervation. The conclusion of our comparison was that the above, in conjunction with other features of the island flap design, such as muscle overlap after sphincter formation and abdominal wall positioning of the sphincter, made the island flap design better suited to stoma sphincter construction.}, }
@article {pmid10696884, year = {2000}, author = {Madoff, RD and Baeten, CG and Christiansen, J and Rosen, HR and Williams, NS and Heine, JA and Lehur, PA and Lowry, AC and Lubowski, DZ and Matzel, KE and Nicholls, RJ and Seccia, M and Thorson, AG and Wexner, SD and Wong, WD}, title = {Standards for anal sphincter replacement.}, journal = {Diseases of the colon and rectum}, volume = {43}, number = {2}, pages = {135-141}, doi = {10.1007/BF02236969}, pmid = {10696884}, issn = {0012-3706}, mesh = {Anal Canal/*surgery ; Artificial Organs ; Digestive System Surgical Procedures/methods/*standards ; Electric Stimulation ; Fecal Incontinence/*surgery ; Humans ; Lumbosacral Plexus/physiology ; Muscle, Skeletal/innervation/physiology/transplantation ; Patient Selection ; Practice Guidelines as Topic ; Quality of Life ; Plastic Surgery Procedures/*standards ; }, abstract = {PURPOSE: Anal sphincter replacement offers a new treatment option for patients with severe refractory fecal incontinence or for those who require abdominoperineal resection for localized malignancy. The purpose of this study was to review the current status of anal sphincter replacement, formulate a consensus statement regarding its current use, and outline suggestions for future development.<br><br>METHODS: Four areas of interests were selected: indications for sphincter replacement, continence scoring and quality of life, choice of therapy, and dissemination of new technology. A questionnaire regarding these issues was developed and circulated to working party members; its results served as the basis for this consensus document.<br><br>RESULTS: Both electrically stimulated skeletal muscle neosphincter and artificial anal sphincter are options for patients with end-stage fecal incontinence. Electrically stimulated skeletal muscle neosphincter is also appropriate for reconstruction after surgical excision of the anorectum in selected cases. Avoidance of complications requires strict attention to sterile technique, prophylactic antibiotics, and deep venous thrombus prophylaxis. A standardized scoring system is proposed that evaluates both continence and evacuation. Quality of life is a critical endpoint for assessing sphincter replacement, and use of The American Society of Colon and Rectal Surgeons incontinence-specific quality-of-life instrument is recommended. As the efficacy of sphincter replacement becomes proven, dissemination of the technique should occur in a controlled manner to ensure adequate surgeon training, minimization of complications, and optimization of results.<br><br>CONCLUSIONS: Sphincter replacement by electrically stimulated skeletal muscle neosphincter and artificial anal sphincter provide a continent option for patients with end-stage fecal incontinence and those requiring abdominoperineal resection. The guidelines offered in this document are intended to facilitate the controlled and safe development and acceptance of these new techniques.}, }
@article {pmid10683554, year = {2000}, author = {Ciocca, M}, title = {Clinical course and consequences of hepatitis A infection.}, journal = {Vaccine}, volume = {18 Suppl 1}, number = {}, pages = {S71-4}, doi = {10.1016/s0264-410x(99)00470-3}, pmid = {10683554}, issn = {0264-410X}, mesh = {Adolescent ; Argentina/epidemiology ; Child ; Child, Preschool ; Hepatitis A/epidemiology/*etiology/surgery ; Humans ; Infant ; Liver Failure/etiology/surgery ; Liver Transplantation ; Prognosis ; Risk Factors ; }, abstract = {Hepatitis A virus (HAV) is a small, non-enveloped RNA virus belonging to the Picornaviridae, for which only one serotype has been identified. Transmission is usually through the faecal-oral route by person-to-person contact. The most common risk factors are household or sexual contact with a sufferer, attendance or working at a day-care centre, international travel, and association with food or waterborne outbreaks; 55% of cases have no identifiable risk factors. HAV infection may be symptomatic or asymptomatic, and shows three phases. Virus is shed during the incubation phase, anti-HAV IgM appears during the symptomatic phase and can be used for diagnosis, and anti-HAV IgG appears at the same time but persists lifelong. Unusual clinical manifestations of hepatitis A include cholestatic, relapsing and fulminant hepatitis. Hepatitis A accounts for 93% of cases of acute hepatitis in Argentina, including 7% of atypical clinical cases. Hepatitis A is the major cause of fulminant hepatitis, and has been reported to account for 10% of liver transplants in children in France and 20% in Argentina. One-year survival after liver transplantation is 64%. Prevention must be considered as the main means of averting this severe illness.}, }
@article {pmid10673699, year = {2000}, author = {Chakrabarti, S and Collingham, KE and Stevens, RH and Pillay, D and Fegan, CD and Milligan, DW}, title = {Isolation of viruses from stools in stem cell transplant recipients: a prospective surveillance study.}, journal = {Bone marrow transplantation}, volume = {25}, number = {3}, pages = {277-282}, doi = {10.1038/sj.bmt.1702164}, pmid = {10673699}, issn = {0268-3369}, mesh = {Adenoviridae/isolation &amp; purification ; Adolescent ; Adult ; Combined Modality Therapy ; Cytomegalovirus Infections/blood ; Enterovirus/isolation &amp; purification ; Enterovirus B, Human/isolation &amp; purification ; Feces/*virology ; Female ; Gastroenteritis/virology ; Graft vs Host Disease/virology ; Hematologic Neoplasms/complications/therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Time Factors ; Transplantation Conditioning ; Transplantation, Autologous/adverse effects ; Transplantation, Homologous/adverse effects ; Viruses/*isolation &amp; purification ; Whole-Body Irradiation ; }, abstract = {We prospectively examined stool specimens for enteric viruses in 75 stem cell transplant recipients (autologous 48, allogeneic 27) to determine the frequency and significance of these infections. Only six patients (8%) had a positive isolate. Five of these were allograft recipients (18%) compared to one autograft recipient (2%) (P = 0.02). Unrelated donor BMT recipients were at the highest risk for a viral isolate (OR = 10.5). Adenovirus was the commonest isolate (four patients). One patient each had an echovirus, enterovirus and small round structured virus identified. No correlation was found between the severity of gastro-intestinal symptoms and detection of a viral pathogen. There was no correlation with GVHD or CMV status. The only risk factor identified for isolation of an enterovirus was allogeneic BMT from an unrelated donor. There was a negative correlation with PBSC grafts. All the patients infected with an enteric virus had concomitant infection with other pathogens, compared to only 18% of uninfected patients (P = 0.001). The non-relapse mortality of the infected patients was 50% and only 7% in the uninfected patients (P = 0.01, OR = 12.5), although the isolated virus was the direct cause of death in one patient only. This study indicates a low rate of enteric virus isolation in recipients of PBSC grafts, both autologous and allogeneic. However, unrelated donor BMT is associated with a higher risk of enteric virus infection and an adverse outcome. Bone Marrow Transplantation (2000) 25, 277-282.}, }
@article {pmid10673672, year = {2000}, author = {Kapur, D and Dorsky, D and Feingold, JM and Bona, RD and Edwards, RL and Aslanzadeh, J and Tutschka, PJ and Bilgrami, S}, title = {Incidence and outcome of vancomycin-resistant enterococcal bacteremia following autologous peripheral blood stem cell transplantation.}, journal = {Bone marrow transplantation}, volume = {25}, number = {2}, pages = {147-152}, doi = {10.1038/sj.bmt.1702123}, pmid = {10673672}, issn = {0268-3369}, mesh = {Adolescent ; Adult ; Aged ; Anti-Bacterial Agents/therapeutic use ; Bacteremia/complications/*drug therapy/epidemiology/microbiology ; Blood Transfusion, Autologous/adverse effects ; Child ; Child, Preschool ; Combined Modality Therapy/adverse effects ; Enterococcus/*drug effects/isolation &amp; purification ; Feces/microbiology ; Female ; Gram-Positive Bacterial Infections/complications/*drug therapy/epidemiology/microbiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Incidence ; Infant ; Male ; Middle Aged ; Neoplasms/complications/drug therapy/microbiology/therapy ; Recurrence ; Retrospective Studies ; Treatment Outcome ; *Vancomycin Resistance ; }, abstract = {A retrospective evaluation of 321 consecutive recipients of high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of vancomycin-resistant enterococcal (VRE) bacteremia. Ten patients developed VRE bacteremia at a median of 6 days following PBSCT. Nine isolates were Enterococcus faecium and one was E. faecalis. The median duration of bacteremia was 5 days. The central venous catheter was removed in seven individuals. Nine patients were treated with a variety of antimicrobial agents including quinupristin-dalfopristin, chloramphenicol, doxycycline, oral bacitracin, co-trimoxazole, and nitrofurantoin. Bacteremia resolved without adverse sequelae in seven patients. Two individuals who died of other causes had persistent or relapsed bacteremia at the time of death. An additional patient suffered multiple relapses of VRE bacteremia and died as a result of VRE endocarditis 605 days following PBSCT. Mortality as a direct result of VRE bacteremia was 10% in this series. The optimal type and duration of treatment of VRE bacteremia has not been clearly defined. Therefore, we perform weekly stool surveillance cultures for VRE in our hospitalized transplant population and apply strict barrier precautions in those individuals in whom stool colonization has been identified. Furthermore, the empiric use of vancomycin has been restricted. Bone Marrow Transplantation (2000) 25, 147-152.}, }
@article {pmid10651601, year = {2000}, author = {Nosanchuk, JD and Shoham, S and Fries, BC and Shapiro, DS and Levitz, SM and Casadevall, A}, title = {Evidence of zoonotic transmission of Cryptococcus neoformans from a pet cockatoo to an immunocompromised patient.}, journal = {Annals of internal medicine}, volume = {132}, number = {3}, pages = {205-208}, doi = {10.7326/0003-4819-132-3-200002010-00006}, pmid = {10651601}, issn = {0003-4819}, mesh = {Aged ; Animals ; *Animals, Domestic ; *Birds ; Cryptococcosis/*transmission/veterinary ; Cryptococcus neoformans/classification/isolation &amp; purification ; Female ; Humans ; *Immunocompromised Host ; Kidney Transplantation/immunology ; Serotyping ; *Zoonoses ; }, abstract = {BACKGROUND: Although cryptococcosis has been associated with birds for almost 50 years, point sources for infection have not been identified.<br><br>OBJECTIVE: To document zoonotic transmission of Cryptococcus neoformans.<br><br>DESIGN: Case report.<br><br>SETTING: A home in Boston, Massachusetts.<br><br>PATIENT: A 72-year-old woman who received a diagnosis of cryptococcal meningitis in November 1998. The patient, who had been taking immunosuppressant drugs since undergoing renal transplantation in 1989, owned a pet cockatoo.<br><br>MEASUREMENTS: Cryptococcus neoformans was isolated from the feces of the cockatoo. Isolates from excreta and from the patient were compared by using biochemical profiles, monoclonal antibody binding patterns, restriction fragment length polymorphism analysis, and karyotyping.<br><br>RESULTS: The isolates from the patient and the cockatoo had identical biochemical profiles, the same monoclonal antibody immunofluorescence patterns, and indistinguishable patterns on restriction fragment length polymorphism analysis and karyotyping.<br><br>CONCLUSIONS: The indistinguishable patient and cockatoo isolates strongly suggest that the patient's infection resulted from exposure to aerosolized cockatoo excreta. Although the incidence of cryptococcal infection due to such exposure is unknown, it may be prudent to advise immunocompromised patients to avoid pet birds and avian excreta.}, }
@article {pmid10649835, year = {1999}, author = {Mitchell, WG}, title = {Neurocysticercosis and acquired cerebral toxoplasmosis in children.}, journal = {Seminars in pediatric neurology}, volume = {6}, number = {4}, pages = {267-277}, doi = {10.1016/s1071-9091(99)80025-4}, pmid = {10649835}, issn = {1071-9091}, mesh = {Anti-Inflammatory Agents/therapeutic use ; Anticonvulsants/therapeutic use ; Antiparasitic Agents/therapeutic use ; Child ; Diagnosis, Differential ; Epilepsy/parasitology/prevention &amp; control ; Humans ; *Neurocysticercosis/diagnosis/epidemiology/parasitology/therapy ; Neurosurgical Procedures ; Steroids ; Tomography, X-Ray Computed ; *Toxoplasmosis, Cerebral/diagnosis/epidemiology/parasitology/therapy ; United States/epidemiology ; }, abstract = {Neurocysticercosis, prevalent wherever pigs are raised in the presence of poor sanitation, is the most common identifiable cause of new-onset epilepsy throughout the developing world. As immigration patterns have changed, children with neurocysticercosis are seen throughout the United States. Acute cysticercosis, the most common manifestation in children, reflects the host response to the dying parasite. Children typically present with seizures and have an excellent prognosis. Neuroimaging demonstrates a single ring or nodular enhancing lesion surrounded by edema. Short-term anticonvulsant therapy is indicated, but treatment with antiparasitic agents is not required. Other forms, such as active cysts (intact organism), intraventricular or subarachnoid racemous cysticercosis, and cysticercal meningoencephalitis, are less common manifestations of parasitic infection. Toxoplasmosis, caused by the parasite Toxoplasma gondii, can be acquired by ingestion of infected undercooked meat or from oocytes shed in cat feces. Acquired cerebral toxoplasmosis, due to primary or reactivated infections, rarely occurs in immunocompetent children. In children who are immunodeficient as the result of AIDS, chemotherapy, tissue transplantation, or congenital immunodeficiency, toxoplasmosis may be difficult to distinguish from cerebral lymphoma. A variety of techniques, including neuroimaging, Thallium-201 SPECT, polymerase chain reaction analysis of CSF, and special histological methods, may be used to diagnose acquired toxoplasmosis. Antiparasitic therapy, using pyrimethamine and sulfadiazine, and serial neuroimaging often enable clinicians to differentiate toxoplasmosis from other central nervous system lesions. Toxoplasmosis may respond to other antimicrobials, including macrolide antibiotics, dapsone, clinidamycin, and atovaquone. Suppressive treatment is generally required for life in immunodeficient patients. Immunodeficient children with acquired toxoplasmosis have high rates of mortality and neurological sequelae.}, }
@article {pmid11104588, year = {2000}, author = {Pencharz, PB and Durie, PR}, title = {Pathogenesis of malnutrition in cystic fibrosis, and its treatment.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {19}, number = {6}, pages = {387-394}, doi = {10.1054/clnu.1999.0079}, pmid = {11104588}, issn = {0261-5614}, mesh = {Basal Metabolism/physiology ; Cystic Fibrosis/*complications/metabolism/therapy ; Diet ; Dietary Fats/administration &amp; dosage ; Energy Metabolism ; Feces/chemistry ; Gastroesophageal Reflux/complications/drug therapy ; Glycosuria ; Humans ; Lung Diseases/metabolism ; Malabsorption Syndromes/complications/therapy ; Nutrition Assessment ; Nutrition Disorders/*etiology/*therapy ; Nutritional Requirements ; Nutritional Support ; }, abstract = {PATHOGENESIS: We have developed a model of the pathogenesis of malnutrition in cystic fibrosis. It consists of the relationship between nutrient balance and nutrient requirement. The validation has been conducted with respect to energy, but the same general principals can be applied to any nutrient. A patient with CF either loses weight or fails to grow normally if their absorbed energy intake is less than their total daily energy expenditure. Multiple factors have the potential to contribute to reduced energy intake including, anorexia, gastroeosophageal (GE) reflux leading to vomiting and hence food loss, as well as maldigestion. Another more recently recognized source of energy loss, is glucosuria as a result of CF related diabetes (CFRD). Conversely, lung inflammation appears to be related to increases in resting metabolic rate (RMR). Acute exacerbations of the chronic lung disease increases RMR which returns to a basal level some weeks after the inflammation is treated. In clinically stable patients with CF, RMR rises in a quadratic fashion as lung function falls. When FEV(1)is >85% predicted RMR is not different from controls, but it rises in a curvilinear fashion as FEV(1)falls. Initially it appears that patients adapt to their increased RMR by reducing their activity so their total daily energy expenditure (TDEE) is often no higher than controls. But this is by no means always the case. Furthermore good lung care requires CF patients to be involved in aerobic activities, hence their TDEE would rise. Although there has been considerable interest as to whether the genetic defect has an energy wasting effect, it appears genetic factors have little or no effect on RMR.<br><br>TREATMENT: This starts with making an energy diagnosis. First, a 3 day faecal fat balance study is conducted. This provides information with regard to intake as well as to maldigestion. In addition a history of GE reflux is sought, since it can readily be treated with H(2)-blockers. If significant fat malabsorption exists, efforts are made to improve pancreatic enzyme dose and function. The possibility of CFRD also needs to be considered. We measure the RMR of the patient using open circuit indirect calorimetry. Recommendations for diet therapy are based on estimated TDEE, which is determined from RMR taking into account faecal losses. Diet therapy places the emphasis on increasing the fat content of the diet. We have conducted a study to determine whether or not oral supplements help increase TDEE and they did not; they merely replaced food energy. Conversely, nocturnal gastrostomy supplemental feeding, while reducing voluntary food energy intake by about 20%, does result in a significant increase in total daily energy intake. Our target is to achieve a completely normal nutritional status. Long term follow-up of these patients has shown significantly better survival in patients who achieve normal nutritional status. The advent of lung transplantation has added another dimension. In our experience, following a successful lung transplant, most patients no longer need their supplemental gastrostomy feeding.<br><br>SUMMARY: Our clinic policy is to encourage a high fat diet (35-40% total energy) and our patients grow normally in height and weight until their lung disease deteriorates significantly. Patients who develop a negative energy balance seldom if ever respond to diet therapy and hence are candidates for supplemental nocturnal gastrostomy feeds. Gastrostomy fed patients constitute 3 to 5% of our total CF population of approximately 590 patients.}, }
@article {pmid10594503, year = {1999}, author = {Mander, BJ and Wexner, SD and Williams, NS and Bartolo, DC and Lubowski, DZ and Oresland, T and Romano, G and Keighley, MR}, title = {Preliminary results of a multicentre trial of the electrically stimulated gracilis neoanal sphincter.}, journal = {The British journal of surgery}, volume = {86}, number = {12}, pages = {1543-1548}, doi = {10.1046/j.1365-2168.1999.01285.x}, pmid = {10594503}, issn = {0007-1323}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/*physiopathology ; Electric Stimulation Therapy/*methods ; Fecal Incontinence/physiopathology/*surgery ; Female ; Humans ; Male ; Manometry ; Middle Aged ; *Muscle Contraction ; Muscle, Skeletal/*transplantation ; Prospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: The electrically stimulated gracilis neoanal sphincter was initially developed to treat refractory incontinence. Good early results were reported from the two centres that pioneered the technique. The aim of this study was to assess the operation in a prospective multicentre setting.<br><br>METHODS: The procedure was performed on 64 patients from seven centres worldwide and was performed in stages. All patients were evaluated clinically and manometrically before and after operation.<br><br>RESULTS: There was a high incidence of infective and hardware-related complications. At a median of 10 months following closure of the defunctioning stoma 56 per cent had experienced a good functional result. The major functional problems comprised evacuatory difficulties experienced by 25 per cent.<br><br>CONCLUSION: The technique is effective in treating otherwise refractory incontinence. It is, however, a complex procedure and the morbidity rate may be high, particularly during the learning curve, factors that necessitate careful patient selection. Presented to the Association of Surgeons of Great Britain and Ireland in Bournemouth, UK, April 1997 and the European Council of Coloproctology in Edinburgh, UK, June 1997; and published in abstract form as Br J Surg 1997; 88(Suppl): 39 and Int J Colorectal Dis 1997; 12: 144}, }
@article {pmid10592937, year = {1999}, author = {Saïd, S and Nevez, G and Morinière, P and Fournier, A and Raccurt, CP}, title = {[Hemodialysis and strongyloidiasis: a presumed cause of eosinophilia able to mask the other].}, journal = {Nephrologie}, volume = {20}, number = {6}, pages = {343-346}, pmid = {10592937}, issn = {0250-4960}, mesh = {Aged ; Animals ; Antinematodal Agents/therapeutic use ; Eosinophilia/*etiology/parasitology ; Feces/parasitology ; Humans ; Ivermectin/therapeutic use ; Kidney Failure, Chronic/complications/parasitology ; Male ; *Renal Dialysis ; Strongyloides stercoralis/isolation &amp; purification ; Strongyloidiasis/*complications/*diagnosis/drug therapy ; Thiabendazole/therapeutic use ; }, abstract = {The authors report a case of recurrent strongyloidiasis in a former French soldier of the Indochina colonial war (1946-54). Strongyloidiasis was associated with inaugural renal failure (acute steroid-resistant interstitial-type), requiring permanent hemodialysis. Despite antiparasitic treatment, relapse with digestive and pulmonary symptoms occurred 10 years later, following chronic eosinophilia. This observation emphasises that in dialysed subjects, eosinophilia should always stimulate a search for parasitic etiologies before incriminating dialysis-material allergy. Strongyloidiasis is a self-perpetuating helminthiasis whose distribution area is far greater than the intertropical zone. It can be completely asymptomatic, appear as late digestive complications and be responsible for bacteraemic peaks with septic visceral localizations. It causes a chronic oscillating eosinophilia. Diagnosis is usually performed by iterative stool examinations by Baermann technique in order to detect Strongyloides stercoralis rhabditoid larvae. In dialysed patients with unexplained eosinophilia awaiting renal transplant, the options of systematic thiabendazole (50 mg/kg) or ivermectine (0.2 mg/kg) single-dose to overcame the risk of disseminated strongyloidiasis induced by immunosuppressive post-transplantation therapy could be debated.}, }
@article {pmid10583295, year = {1999}, author = {Maurer, CA and Z'graggen, K and Zimmermann, W and Häni, HJ and Mettler, D and Büchler, MW}, title = {Experimental study of neorectal physiology after formation of a transverse coloplasty pouch.}, journal = {The British journal of surgery}, volume = {86}, number = {11}, pages = {1451-1458}, doi = {10.1046/j.1365-2168.1999.01256.x}, pmid = {10583295}, issn = {0007-1323}, mesh = {Animals ; Colon/blood supply/surgery ; Gastrointestinal Transit/physiology ; Laser-Doppler Flowmetry/methods ; Manometry/methods ; Proctocolectomy, Restorative/*methods ; Radiography ; Rectum/diagnostic imaging/pathology/*physiology ; Swine ; }, abstract = {BACKGROUND: A novel transverse coloplasty pouch (TCP) with a larger neorectal volume than a straight coloanal anastomosis (CAA) but a smaller volume than a short colonic J pouch (CJP) may improve short-term function after rectal excision.<br><br>METHODS: Twelve pigs were investigated 6 weeks after complete rectal excision followed by reconstruction with a CAA, CJP or TCP. The results were compared with findings in the normal pig rectum.<br><br>RESULTS: The colonic transit times assessed by radio-opaque marker transit were 24 h for CAA, 60 h for CJP and 32 h for TCP. Non-operated control pigs had a mean transit time of 46 h. Pigs that had a CJP developed colonic dilatation and substantial faecal impaction. Colonic electrostimulation induced an adaptive relaxation in the normal rectum but a pressure increase in all neorecta, particularly after CAA. The neorectal longitudinal smooth muscle layer in pigs with a TCP was significantly thicker than that in pigs with a CAA or CJP; its thickness was closest to that of the normal pig rectum. Colonic smooth muscle layers 10 cm proximal to the coloanal anastomosis, above the neorecta, were significantly thicker after CJP than after CAA or TCP formation. No significant difference in microcirculation was observed between the three restorative procedures.<br><br>CONCLUSION: Accelerated colonic transit and a lack of adequate relaxation upon endoluminal pressure increase was associated with urgency and incontinence after CAA. Delayed colonic transit, faecal impaction and ineffective muscular hypertrophy due to pouch dilatation and constipation indicated evacuation problems after CJP construction. Functional and morphometric data for TCPs suggested almost normal defaecation. Of the three restorative procedures, the data for TCPs were most similar to those obtained in the normal pig rectum at short-term follow-up.}, }
@article {pmid10582746, year = {1999}, author = {Chauvet, AE and Hogge, GS and Sandin, JA and Lipsitz, D}, title = {Vertebrectomy, bone allograft fusion, and antitumor vaccination for the treatment of vertebral fibrosarcoma in a dog.}, journal = {Veterinary surgery : VS}, volume = {28}, number = {6}, pages = {480-488}, doi = {10.1111/j.1532-950x.1999.00480.x}, pmid = {10582746}, issn = {0161-3499}, mesh = {Animals ; Bone Transplantation/*veterinary ; Cancer Vaccines/*therapeutic use ; Dog Diseases/diagnostic imaging/etiology/*therapy ; Dogs ; Female ; Fibrosarcoma/complications/diagnostic imaging/therapy/*veterinary ; Follow-Up Studies ; Laminectomy/veterinary ; Myelography/veterinary ; Postoperative Care/veterinary ; Spinal Cord Compression/diagnostic imaging/etiology/veterinary ; Spinal Neoplasms/complications/diagnostic imaging/therapy/*veterinary ; }, abstract = {OBJECTIVE: To describe the surgical technique of vertebrectomy with bone allograft fusion and the use of antitumor vaccine for the treatment of a primary vertebral neoplasm in a dog.<br><br>STUDY DESIGN: Case Report.<br><br>ANIMALS OR SAMPLE POPULATION: A 3 year old 32 kg female spayed mixed breed dog with progressive paraplegia.<br><br>METHODS: Myelography was performed to identify an L5 lytic lesion with spinal cord compression. A dorsal laminectomy was performed to decompress the spinal cord and obtain biopsies. Pathologic fracture of the vertebral body two days later was treated with L5 vertebrectomy, cortical allograft implantation, and bilateral plating from L4 to L6. Tumor samples were used to create an autologous cytokine-gene-engineered tumor cell vaccine. Recheck radiographs and neurologic examinations were obtained 1, 2, 7, and 13 months after surgery.<br><br>RESULTS: The histopathologic diagnosis was fibrosarcoma. Although slight osteopenia of the allograft was noted thirteen months after surgery, the allograft and plate fixation remained stable. The patient tolerated the antitumor vaccination protocol well. Two years after the procedures the dog was able to ambulate normally but remained urinary and fecal incontinent.<br><br>Vertebrectomy and cortical allograft implantation with plating permitted this patient to return to a functional lifestyle with its owners.}, }
@article {pmid10560360, year = {1999}, author = {Huijgens, PC and Simoons-Smit, AM and van Loenen, AC and Prooy, E and van Tinteren, H and Ossenkoppele, GJ and Jonkhoff, AR}, title = {Fluconazole versus itraconazole for the prevention of fungal infections in haemato-oncology.}, journal = {Journal of clinical pathology}, volume = {52}, number = {5}, pages = {376-380}, pmid = {10560360}, issn = {0021-9746}, mesh = {Adult ; Aged ; Antifungal Agents/*therapeutic use ; Double-Blind Method ; Female ; Fluconazole/*therapeutic use ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Itraconazole/*therapeutic use ; Male ; Middle Aged ; Mycoses/complications/*prevention &amp; control ; Neutropenia/complications ; Opportunistic Infections/complications/*prevention &amp; control ; Patient Compliance ; Survival Rate ; }, abstract = {AIMS: To compare the efficacy of and tolerance to oral fluconazole and intraconazole in preventing fungal infection in neutropenic patients with haematological malignancies.<br><br>PATIENTS: 213 consecutive, afebrile adult patients treated with or without autologous stem cell transplantation for haematological malignancies.<br><br>METHODS: A randomised, double blind, single centre study. Patients were randomly assigned to receive fluconazole 50 mg or itraconazole 100 mg, both twice daily in identical capsules. An intention to treat analysis was performed on 202 patients, 101 in each group.<br><br>RESULTS: Microbiologically documented systemic fungal infections occurred in four patients in each group. Clinical fungal infection was thought to be present in seven recipients of fluconazole and four of itraconazole. In all 202 patients, 29 proceeded to intravenous amphotericin (amphotericin B), 16 in the fluconazole group and 13 in the itraconazole group. Superficial fungal infection was seen only in three non-compliant patients in the fluconazole group. All these infections were oral. No major differences were noted in the isolates of fungi in mouth washes and fecal samples. Overall mortality was 8.9% (18 deaths; seven in the fluconazole group, 11 in the itraconazole group). Mortality from microbiologically and clinically documented fungal infection was 4.5% (nine deaths; three in the fluconazole group, six in the itraconazole group). Median time to suspected or proven fungal infection was 16 days in both groups. None of these comparisons reached statistical significance (p < 0.05). No major clinical toxicity was noted and compliance was excellent.<br><br>CONCLUSIONS: In neutropenic patients treated for haematological malignancies with or without autologous stem cell transplantation, fluconazole and itraconazole in low doses result in a similar low frequency of fungal disease. Fluconazole may be the preferable drug because of the smaller number of capsules and lack of need for timing relative to meals.}, }
@article {pmid10558958, year = {1999}, author = {Cotte, L and Rabodonirina, M and Chapuis, F and Bailly, F and Bissuel, F and Raynal, C and Gelas, P and Persat, F and Piens, MA and Trepo, C}, title = {Waterborne outbreak of intestinal microsporidiosis in persons with and without human immunodeficiency virus infection.}, journal = {The Journal of infectious diseases}, volume = {180}, number = {6}, pages = {2003-2008}, doi = {10.1086/315112}, pmid = {10558958}, issn = {0022-1899}, mesh = {Adult ; Animals ; *Disease Outbreaks ; Feces/parasitology ; Female ; HIV Infections/*complications ; Humans ; Incidence ; Intestinal Diseases, Parasitic/*epidemiology/parasitology ; Male ; Microsporidia/isolation &amp; purification ; Microsporidiosis/*complications/*epidemiology/parasitology ; Middle Aged ; Organ Transplantation/adverse effects ; Prevalence ; *Water Supply ; }, abstract = {Among 1454 persons whose stool samples (n=5692) were submitted to a reference laboratory for microsporidia assessment from 1993 to 1996, microsporidia were identified in 338 persons: 261 persons infected with human immunodeficiency virus (HIV), 16 transplant patients, and 61 others. Intestinal microsporidiosis appears to be an endemic disease in HIV-positive persons (prevalence, 0.1%) and a sporadic disease in HIV-negative persons (prevalence, <1/1 million). A waterborne outbreak in 200 persons (attack rate, 1% in HIV-positive patients/month) occurred in the 1995 summer, without evidence of fecal contamination of water. No explanation was found before the outbreak ended, several months before the antiprotease era. Factors associated with microsporidiosis diagnosis were HIV infection, male homosexuality, low CD4 cell counts, and diarrhea. The major factor associated with a diagnosis of microsporidiosis during the outbreak was living in an area corresponding to one of the three water distribution subsystems of the town. Lake contamination was suspected.}, }
@article {pmid10550640, year = {1999}, author = {Kissler, HJ and Gepp, H and Schwille, PO}, title = {Orthotopic pancreas transplantation with portal venous drainage in rats. Surgical technique and metabolic effects(*).}, journal = {Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie}, volume = {199}, number = {2}, pages = {73-85}, doi = {10.1007/s004330050134}, pmid = {10550640}, issn = {0300-9130}, mesh = {Animals ; Body Weight ; Drainage ; Fats/metabolism ; Glucose/metabolism ; Glucose Tolerance Test ; Male ; *Pancreas Transplantation ; Portal Vein/surgery ; Rats ; Rats, Inbred Lew ; Rats, Wistar ; }, abstract = {Heterotopic pancreas transplantation in type I diabetic patients does not correct hyperglucagonemia, which is thought to be due to insufficiently suppressed glucagon release by the host pancreas. The diabetogenic effects of glucagon then have to be corrected by higher than normal insulin secretion from the transplant, with the attendant risk of earlier loss of islet cell function, and development of atherosclerosis. To establish whether this situation can be prevented, we investigated glucose homeostasis and blood lipids, as well as fecal fat and chymotrypsin as indicators for pancreatic exocrine function 14 weeks after orthotopic pancreas transplantation in inbred rats. The pancreas was resected before orthotopic transplantation of the donor pancreas with portal venous drainage (n=8). Laparotomized animals served as controls (n=8). Basal plasma glucagon, basal plasma insulin to glucagon molar ratio, and basal and integrated incremental responses of plasma glucose, insulin, and C-peptide after an oral glucose load (2 g/kg body weight) were similar in both groups. However, hepatic insulin clearance was slightly but significantly lower in the transplanted group (1.1+/- 0.1 vs 1.6+/-0.2; P<0.05). Basal plasma levels of free fatty acids, phospholipids, triglycerides, cholesterol, low-density lipoproteins, and high-density lipoproteins were unchanged after transplantation. Also unchanged were fecal fat and chymotrypsin levels, thus indicating preserved pancreatic exocrine function. We concluded that orthotopic pancreas transplantation with portal venous drainage achieves almost optimal metabolic control with respect to endocrine and exocrine pancreatic function as well as blood lipids. This technique could therefore be used to treat combined endocrine and exocrine insufficiency in chronic pancreatitis and thus enlarges the spectrum of indications for pancreas transplantation.}, }
@article {pmid10507491, year = {1999}, author = {Guerard, A and Rabodonirina, M and Cotte, L and Liguory, O and Piens, MA and Daoud, S and Picot, S and Touraine, JL}, title = {Intestinal microsporidiosis occurring in two renal transplant recipients treated with mycophenolate mofetil.}, journal = {Transplantation}, volume = {68}, number = {5}, pages = {699-707}, doi = {10.1097/00007890-199909150-00017}, pmid = {10507491}, issn = {0041-1337}, mesh = {Adult ; Animals ; Feces/parasitology ; Humans ; Immunosuppressive Agents/*adverse effects/therapeutic use ; Intestines/*parasitology ; *Kidney Transplantation ; Male ; Microsporida/*isolation &amp; purification ; Middle Aged ; Mycophenolic Acid/adverse effects/*analogs &amp; derivatives/therapeutic use ; Opportunistic Infections/*chemically induced ; *Postoperative Complications ; Protozoan Infections/*chemically induced ; }, abstract = {BACKGROUND: Intestinal microsporidiosis is a major cause of chronic diarrhea and malabsorption in patients with human immunodeficiency virus. Its occurrence in transplant recipients has exceptionally been reported to date.<br><br>METHODS: We report what we believe are the first two cases of intestinal microsporidiosis in renal transplant recipients. The patients were treated with mycophenolate mofetil.<br><br>RESULTS: The clinical presentation was chronic diarrhea with massive weight loss. Stool analysis revealed microsporidian spores, identified as Enterocytozoon bieneusi spores by polymerase chain reaction. The onset of this opportunistic infection in these two patients is believed to be secondary to an increase in immunosuppression after azathioprine replacement by mycophenolate mofetil. The withdrawal of mycophenolate mofetil led to clinical recovery.<br><br>CONCLUSION: The incidence of microsporidiosis will probably increase in transplant recipients treated with powerful immunosuppressants. Therefore, we recommend a systematic search for microsporidian spores in stool specimens in cases of unexplained diarrhea in these patients.}, }
@article {pmid10459819, year = {1999}, author = {Perea, S and Hidalgo, M and Arcediano, A and Ramos, MJ and Gomez, C and Hornedo, J and Lumbreras, C and Folgueira, D and Cortes-Funes, H and Rodriguez-Noriega, A}, title = {Incidence and clinical impact of fluoroquinolone-resistant Escherichia coli in the faecal flora of cancer patients treated with high dose chemotherapy and ciprofloxacin prophylaxis.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {44}, number = {1}, pages = {117-120}, doi = {10.1093/jac/44.1.117}, pmid = {10459819}, issn = {0305-7453}, mesh = {Adult ; Anti-Infective Agents/*pharmacology/therapeutic use ; *Antibiotic Prophylaxis ; Antineoplastic Agents/therapeutic use ; Bacteremia/microbiology ; Ciprofloxacin/pharmacology/*therapeutic use ; Combined Modality Therapy ; Drug Resistance, Microbial ; Escherichia coli/*drug effects/isolation &amp; purification ; Feces/*microbiology ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Neoplasms/drug therapy/*microbiology/therapy ; }, abstract = {This study evaluated the susceptibility of Escherichia coli to quinolones in 72 stool samples collected from 31 patients with solid tumours who had undergone high dose chemotherapy (HDC) and peripheral blood stem-cell (PBSC) rescue with ciprofloxacin prophylaxis. Samples were obtained at admission, after completing prophylaxis and three months later. All E. coli strains isolated from baseline samples were susceptible to quinolones. Fluoroquinolone-resistant E. coli strains were isolated in 10 (32%) patients in the second sample. In eight of these patients isolates were susceptible 3 months later. No patient developed infection due to fluorquinolone-resistant E. coli. No differences were observed in outcome between patients with susceptible and resistant flora.}, }
@article {pmid10411280, year = {1999}, author = {Mocchegiani, E and Perissin, L and Santarelli, L and Tibaldi, A and Zorzet, S and Rapozzi, V and Giacconi, R and Bulian, D and Giraldi, T}, title = {Melatonin administration in tumor-bearing mice (intact and pinealectomized) in relation to stress, zinc, thymulin and IL-2.}, journal = {International journal of immunopharmacology}, volume = {21}, number = {1}, pages = {27-46}, doi = {10.1016/s0192-0561(98)00067-8}, pmid = {10411280}, issn = {0192-0561}, mesh = {Animal Feed/analysis ; Animals ; Corticosterone/blood ; Disease Progression ; Feces/chemistry ; Female ; Interleukin-2/*metabolism ; Lung Neoplasms/secondary ; Melatonin/*pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Neoplasm Transplantation ; Neoplasms, Experimental/*metabolism/pathology ; Pineal Gland/*physiology ; Stress, Psychological/*metabolism ; Thymic Factor, Circulating/*metabolism ; Water/analysis ; Zinc/blood/*metabolism/urine ; }, abstract = {Melatonin (MEL) may counteract tumors through a direct oncostatic role. MEL is also an antistress agent with immunoenhancing properties against tumors due to a suppressive role of MEL on corticosterone release. Rotational stress (RS) (spatial disorientation) facilitates metastasis progression in mice. Also, MEL counteracts tumors because of its influence on immune responses via the metabolic zinc pool, which, is reduced in tumors and stress. Zinc is required for normal thymic endocrine activity (i.e. thymulin) and interleukin-2 (IL-2) production. Because in vivo data is still controversial, exogenous MEL treatment (22 days in drinking water) in both intact and pinealectomized (px) mice bearing Lewis lung carcinoma leads to significant decrements of metastasis volume, restoration of the negative crude zinc balance, recovery of thymulin activity and increment of IL-2 exclusively in intact and px tumor bearing mice subjected to RS. Significant inverse correlations are found in both stressed intact and px tumor bearing mice after MEL treatment between zinc and corticosterone (r = 0.78, P < 0.01; r = 0.80, P < 0.01, respectively). Positive correlations between zinc and IL-2 (r = 0.75, P < 0.01; r = 0.73, P < 0.01, respectively) or thymulin (r = 0.75, P < 0.01; r = 0.82, P < 0.01, respectively) are observed in same models of mice. These findings suggest a MEL action to decrease metastasis mediated by a possible interplay between zinc and MEL, via corticosterone, with consequent restoration of thymic efficiency and IL-2 production. MEL as an antistress agent with immunoenhancing properties in cancer deserves further consideration.nuclear factor-kb; POMC, proopiomelanocortin; Px, pinealectomized mice; RIA, radioimmunoassay; RS, rotational stress; SDI, stressed intact mice; SDPx, stressed pinealectomized mice; TNF-alpha, tumor necrosis factor-alpha; ZnFTS, active zinc-bound thymulin; ZnFTS + FTS, total thymulin.}, }
@article {pmid10392924, year = {1999}, author = {Uchida, H and Yoshida, T and Kobayashi, E and Mizuta, K and Fujimura, A and Miyata, M and Kawarasaki, H and Hashizume, K}, title = {Experimental small bowel transplantation using newborn intestine in rats: I. Lipid absorption restored after transplantation of nonvascularized graft.}, journal = {Journal of pediatric surgery}, volume = {34}, number = {6}, pages = {1007-1011}, doi = {10.1016/s0022-3468(99)90779-0}, pmid = {10392924}, issn = {0022-3468}, mesh = {Animals ; Animals, Newborn ; Electromyography ; Female ; *Intestinal Absorption ; Intestine, Small/*metabolism/*transplantation ; *Lipid Metabolism ; Male ; Omentum/surgery ; Rats ; Rats, Inbred Lew ; }, abstract = {BACKGROUND/PURPOSE: Utilizing the characters of neovascularized activity of newborn organs, the authors developed a rat model of small bowel transplantation with a free graft of newborn intestine into the recipient's omentum.<br><br>METHODS: Segmental intestine from newborn rats were grafted into the omentum without vascular anastomosis in a syngeneic combination (n = 19). The transplanted intestine was examined morphologically and electrophysiologically 4 weeks after grafting. Then, recipients' small intestine was totally substituted by the transplanted newborn intestine, and recipients' survival was recorded after orthotopical reconstruction. During the experimental periods, feces of these rats were collected, and total lipid excretion was measured. The short-gut rats, whose small bowel was totally resected, served as a control (n = 12).<br><br>RESULTS: Thirteen of 19 grafts (68.4%) were judged as a histologically mature intestine. They showed typical slow waves that were identical to those of native small intestine. After all of the mature grafts were interposed, six recipients (46.2%) survived longer than 15 weeks. Control short gut animals severely lost weight and died except for one.<br><br>CONCLUSION: Newborn intestinal transplantation could restore severe weight loss in the short-gut rats and save them.}, }
@article {pmid10378928, year = {1999}, author = {Lanmüller, H and Sauermann, S and Unger, E and Schnetz, G and Mayr, W and Bijak, M and Rafolt, D and Girsch, W}, title = {Battery-powered implantable nerve stimulator for chronic activation of two skeletal muscles using multichannel techniques.}, journal = {Artificial organs}, volume = {23}, number = {5}, pages = {399-402}, doi = {10.1046/j.1525-1594.1999.06359.x}, pmid = {10378928}, issn = {0160-564X}, mesh = {Diaphragm/innervation/physiology ; *Electric Power Supplies ; Electric Stimulation Therapy/*instrumentation ; Electronics, Medical/instrumentation ; Equipment Design ; Fecal Incontinence/surgery ; Humans ; Motor Neurons/physiology ; Muscle Contraction/physiology ; Muscle, Skeletal/innervation/*physiology/transplantation ; Phrenic Nerve/physiology ; *Prostheses and Implants ; Respiration ; Time Factors ; Titanium ; }, abstract = {Chronic activation of skeletal muscle is used clinically in representative numbers for diaphragm pacing to restore breathing and for dynamic graciloplasty to achieve fecal continence. The 3 different stimulation techniques currently used for electrophrenic respiration (EPR) all apply high frequency powered implants. It was our goal to make these stimulation methods applicable for EPR by a battery-powered nerve stimulator that would maximize the patient's freedom of movement. Additionally, the system should allow the implementation of multichannel techniques and alternating stimulation of 2 skeletal muscles as a further improvement in graciloplasty. Generally, the developed implantable nerve stimulator can be used for simultaneous and alternating activation of 2 skeletal muscles. Stimulation of the motor nerve is achieved by either single channel or multichannel methods. Carousel stimulation and sequential stimulation can be used for graciloplasty as well as for EPR. For EPR we calculated an operating time of the implant battery of 4.1 years based on the clinically used stimulation parameters with carousel stimulation. The multichannel pulse generator is hermetically sealed in a titanium case sized 65 x 17 mm (diameter x height) and weighs 88 g.}, }
@article {pmid10348790, year = {1999}, author = {Möller, A and Iwasaki, K and Kawamura, A and Teramura, Y and Shiraga, T and Hata, T and Schäfer, A and Undre, NA}, title = {The disposition of 14C-labeled tacrolimus after intravenous and oral administration in healthy human subjects.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {27}, number = {6}, pages = {633-636}, pmid = {10348790}, issn = {0090-9556}, mesh = {Administration, Oral ; Aged ; Area Under Curve ; Biological Availability ; Carbon Radioisotopes ; Cross-Over Studies ; Enzyme-Linked Immunosorbent Assay ; Feces/chemistry ; Humans ; Immunosuppressive Agents/administration &amp; dosage/blood/*pharmacokinetics/urine ; Injections, Intravenous ; Male ; Middle Aged ; Tacrolimus/administration &amp; dosage/blood/*pharmacokinetics/urine ; }, abstract = {Tacrolimus is a macrolide lactone with potent immunosuppressive properties. It has been shown in clinical studies to prevent allograft rejection. The pharmacokinetics of tacrolimus in healthy subjects and transplant patients has been described in earlier studies using immunoassay methods; however, detailed information on the absorption, distribution, metabolism, and excretion of tacrolimus using a radiolabeled drug is lacking. The objective of the present study was to characterize the disposition of tacrolimus after single i.v. (0.01 mg/kg) and oral (0.05 mg/kg) administration of 14C-labeled drug in six healthy subjects. Tacrolimus was absorbed rapidly after oral dosing with a mean Cmax and Tmax of 42 ng/ml and 1 h, respectively. The oral bioavailability was about 20%. After i.v. and oral dosing, most of the administered dose was recovered in feces, suggesting that bile is the principal route of elimination. Urinary excretion accounted for less than 3% of total administered dose. In systemic circulation, unchanged parent compound accounted for nearly all the radioactivity; however, less than 0.5% of unchanged drug was detectable in feces and urine. The excretion of the metabolites was formation-rate-limited. The mean total body clearance at 37.5 ml/min was equivalent to about 3% of the liver blood flow. Renal clearance was less than 1% of the total body clearance. The mean elimination half-life was 44 h.}, }
@article {pmid10344361, year = {1999}, author = {Katai, K and Tanaka, H and Tatsumi, S and Fukunaga, Y and Genjida, K and Morita, K and Kuboyama, N and Suzuki, T and Akiba, T and Miyamoto, K and Takeda, E}, title = {Nicotinamide inhibits sodium-dependent phosphate cotransport activity in rat small intestine.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {14}, number = {5}, pages = {1195-1201}, doi = {10.1093/ndt/14.5.1195}, pmid = {10344361}, issn = {0931-0509}, mesh = {Animals ; Carrier Proteins/genetics/*metabolism ; Female ; Gene Expression/drug effects ; Humans ; In Vitro Techniques ; Ion Transport/drug effects ; Jejunum/*drug effects/*metabolism ; Microvilli/metabolism ; Niacinamide/*pharmacology ; Oocytes/drug effects/metabolism ; Phosphates/*metabolism ; Rats ; Rats, Wistar ; Sodium/*metabolism ; Sodium-Phosphate Cotransporter Proteins ; *Symporters ; Xenopus laevis ; }, abstract = {BACKGROUND: We recently reported that the administration of niceritorol (a nicotinic acid derivative which improves lipid metabolism and peripheral circulation, and is used for the treatment of hyperlipidaemia and impaired peripheral circulation) to patients with hyperphosphataemia undergoing dialysis decreased the serum phosphate (Pi) concentration. We found that this was due to an acceleration of faecal Pi excretion by niceritrol.<br><br>METHODS: Intestinal brush border membrane vesicles (BBMVs) were prepared from rat jejunum, and the Na+-dependent and Na+-independent Pi transport activities in these vesicles were measured. In addition, the functional Pi transporter from rat small intestine was injected in Xenopus oocytes, and the effect of nicotinamide on the levels of its expression were measured by northern blotting.<br><br>RESULTS: The Na+-dependent component was significantly decreased in the BBMVs isolated from rats treated with nicotinamide, while the Na+-independent component was not changed. Kinetic studies demonstrated that the decreased activity was due to reduction of the Vmax value and not an elevation of the Km values. When poly(A)+RNA from rats treated with nicotinamide was microinjected into Xenopus oocytes, the Pi transport activity was significantly decreased compared with that in the control animals. In addition, there were no significant changes in Na/Pi cotransporters and activators, but the vitamin D receptor mRNA level was reduced to 80% of the control level.<br><br>CONCLUSIONS: These observations suggest that nicotinamide may regulate the expression of a major functional Na/Pi cotransporter in the rat small intestine.}, }
@article {pmid10343205, year = {1998}, author = {Fritsch, C and Lang, K and Bolsen, K and Lehmann, P and Ruzicka, T}, title = {Congenital erythropoietic porphyria.}, journal = {Skin pharmacology and applied skin physiology}, volume = {11}, number = {6}, pages = {347-357}, doi = {10.1159/000029857}, pmid = {10343205}, issn = {1422-2868}, mesh = {Adolescent ; Adult ; Bone and Bones/pathology ; Feces/chemistry ; Female ; Humans ; Male ; Middle Aged ; *Porphyria, Erythropoietic/genetics/pathology/therapy ; Porphyrins/*metabolism ; }, abstract = {Congenital erythropoietic porphyria (CEP) is one of the rarest autosomal-recessive disorders of the porphyrin metabolism caused by the homozygous defect of uroporphyrinogen III cosynthase. High amounts of uroporphyrin I accumulate in all cells and tissues, reflected by an increased erythrocyte porphyrin concentration and excretion of high porphyrin amounts in urine and feces. Dermal deposits of uroporphyrin frequently induce a dramatic phototoxic oxygen-dependent skin damage with extensive ulcerations and mutilations. Splenomegaly and hemolytic anemia are typical internal symptoms. Skeletal changes such as osteolysis and calcifications are frequent. Up to date 130 cases of CEP have been published. Splenectomy and erythrocyte transfusions showed some beneficial effect. Bone marrow transplantation was performed in 3 patients and stem cell transplantation in 1. The best therapy is the avoidance of sunlight. We give a report on our latest cases of CEP.}, }
@article {pmid10332442, year = {1999}, author = {Bruce, RG and el-Galley, RE and Wells, J and Galloway, NT}, title = {Antegrade continence enema for the treatment of fecal incontinence in adults: use of gastric tube for catheterizable access to the descending colon.}, journal = {The Journal of urology}, volume = {161}, number = {6}, pages = {1813-1816}, pmid = {10332442}, issn = {0022-5347}, mesh = {Adult ; Colon/*surgery ; Digestive System Surgical Procedures/methods ; Enema/*methods ; Fecal Incontinence/*therapy ; Female ; Humans ; Male ; Middle Aged ; Stomach/*transplantation ; }, abstract = {PURPOSE: We describe the use of a gastric segment in performing the antegrade continence enema procedure in patients with refractory fecal incontinence.<br><br>MATERIALS AND METHODS: The antegrade continence enema procedure was performed in 4 women and 3 men with refractory neurogenic fecal incontinence. Preoperative evaluation included defecography and anorectal manometry. Operative technique involves tunneling a 10 cm. segment of tubularized stomach isolated along the greater curve with preservation of the right gastroepiploic vessels through the anterior tenia of the colon just distal to the splenic flexure. After the stoma is mature the patient passes a catheter and runs 1 to 2 l. warm tap water through it while seated on the toilet. Digital stimulation may be required to initiate bowel emptying and irrigation is continued until clear.<br><br>RESULTS: Creation of a nonrefluxing catheterizable gastric tube to the descending colon was successful in all 7 patients. At a mean postoperative followup of 22.4 months all patients are continent and use antegrade continence enema irrigation every other day on average. One patient required early revision because of stomal stenosis. Special measures include application of a generic antacid tablet to the stoma and use of a skin barrier.<br><br>CONCLUSIONS: Catheterizable access to the descending colon for the antegrade continence enema procedure more closely approximates normal defecation patterns by emptying ("unloading") the left side of the colon. The stomach is a suitable option in close proximity for this purpose and is especially advantageous when the appendix is not available. The antegrade continence enema procedure using a gastric segment can be safely and effectively performed, and is well suited for use by reconstructive surgeons who are familiar with the Mitrofanoff principle.}, }
@article {pmid10213116, year = {1999}, author = {Saito, T and Kobayashi, E and Ogino, Y and Kaneko, K and Fujimura, A and Miyata, M}, title = {Changes in fecal fat excretion from allo-intestine transplanted rats after discontinuance of immunosuppressive agents.}, journal = {Journal of gastroenterology}, volume = {34}, number = {2}, pages = {182-188}, doi = {10.1007/s005350050241}, pmid = {10213116}, issn = {0944-1174}, mesh = {Animals ; Fats/analysis/*metabolism ; Feces/*chemistry ; Graft Rejection/pathology ; Graft Survival/drug effects ; Guanidines/*pharmacology ; Ileum/drug effects/*metabolism/transplantation ; Immunosuppressive Agents/*pharmacology ; Male ; Rats ; Rats, Inbred Lew ; Rats, Inbred Strains ; Survival Rate ; Time Factors ; Transplantation, Homologous/mortality/pathology/*physiology ; }, abstract = {We have previously shown in a rat model of segmental small bowel transplantation, that an ileal graft was more favorable for lipid absorption than a jejunal graft. In the present study, we investigated changes in the lipid absorption of allo-ileal grafts after the withdrawal of an immunosuppressant (methyldeoxyspergualin; given for 1 or 2 weeks at 2.5mg/kg per day) and compared the findings with the results of histological examinations. Heterotopic segmental small bowel transplantation (SBT) was performed using cuff anastomoses in the inbred rat strain combination DA (RT1a) and LEW (RT1). Orthotopic SBT was performed as reconstruction SBT. Reconstruction after resection of the original intestinal tract of the recipient was performed on the seventh day after heterotopic segmental ileal grafting. For the histological evaluation of graft rejection, we performed biopsies in the heterotopic model and autopsies in the orthotopic model. Fecal fat excretion from the orthotopically reconstructed recipients was measured by Folch's method. One- and 2-week use of methyldeoxyspergualin allowed the heterotopic allografts to remain intact histologically for 16.8+/-5.6 and 25.3+/-3.3 (mean+/-SD) days, respectively, whereas the grafts were rejected at 7.3+/-1.1 days when the immunosuppressive drug was not used. All the recipients in the orthotopic group had died by 19 days after reconstruction. After discontinuance of the immunosuppressive agent, fat excretion in feces in the surviving orthotopic grafted rats had increased markedly prior to histologically assessed heterotopic graft rejection. Evaluation of fecal lipid excretion may be a useful parameter for detecting graft rejection in rats.}, }
@article {pmid10209458, year = {1998}, author = {Ramakrishnan, V and Southern, S and Hart, NB and Tzafetta, K}, title = {Endoscopically assisted gracilis harvest for use as a free and pedicled flap.}, journal = {British journal of plastic surgery}, volume = {51}, number = {8}, pages = {580-583}, doi = {10.1054/bjps.1998.0179}, pmid = {10209458}, issn = {0007-1226}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/surgery ; Endoscopy/*methods ; Fecal Incontinence/*surgery ; Female ; Foot Injuries/surgery ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Plastic Surgery Procedures/*methods ; *Surgical Flaps ; }, abstract = {Endoscopic assistance in soft tissue surgery may prove to greatly aid in the improvement of cosmesis and reduction of morbidity in certain procedures. The scar produced from open gracilis harvest is the most common complaint following surgery. We present five cases of endoscopically assisted gracilis harvest for use as a neosphincter and in foot reconstruction. The operative technique is described.}, }
@article {pmid10193807, year = {1999}, author = {Kuboyama, N and Watanabe, Y and Yamaguchi, M and Sato, K and Suzuki, T and Akiba, T}, title = {Effects of niceritrol on faecal and urinary phosphate excretion in normal rats.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {14}, number = {3}, pages = {610-614}, doi = {10.1093/ndt/14.3.610}, pmid = {10193807}, issn = {0931-0509}, mesh = {Animals ; Body Weight/drug effects ; Calcium/blood ; Eating/drug effects ; Feces/*chemistry ; Hypolipidemic Agents/*pharmacology ; Male ; Niceritrol/*pharmacology ; Phosphates/*metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: Phosphate binders such as aluminium hydroxide and calcium carbonate have several side-effects so that they are not ideal for clinical use. Recently we reported that administration of niceritrol at 750 mg/day to patients with HDL hypocholesterolaemia undergoing dialysis decreased the serum phosphate concentration. To clarify the mechanism of reduction of the serum phosphate concentration by niceritrol in patients undergoing dialysis, the effects of niceritrol on faecal and urinary phosphate excretion were examined in normal rats.<br><br>METHODS: Niceritrol suspension in 5% gum arabic was administered for 4 days in normal rats. Faeces and urine were collected in metabolic cage and analysed for phosphate content.<br><br>RESULTS AND CONCLUSIONS: Faecal phosphate excretion significantly increased in the groups with administration of 100 and 500 mg/kg niceritrol, but not in the group with 20 mg/kg. On the other hand, urinary phosphate excretion was not significantly changed in the groups on 20-500 mg/kg. Retention of phosphate was significantly suppressed in the groups on 100 and 500 mg/kg. A increased faecal phosphate excretion by niceritrol is presumably the mechanism by which serum phosphate concentration is reduced in dialysis patients.}, }
@article {pmid10084747, year = {1998}, author = {Green, M and Barbadora, K}, title = {Recovery of ceftazidime-resistant Klebsiella pneumoniae from pediatric liver and intestinal transplant recipients.}, journal = {Pediatric transplantation}, volume = {2}, number = {3}, pages = {224-230}, pmid = {10084747}, issn = {1397-3142}, support = {5M01 RR00084/RR/NCRR NIH HHS/United States ; }, mesh = {Adolescent ; Ceftazidime/*pharmacology ; *Cephalosporin Resistance ; Child ; Child, Preschool ; Electrophoresis, Gel, Pulsed-Field ; Feces/microbiology ; Humans ; Infant ; Intestine, Small/*transplantation ; *Kidney Transplantation ; Klebsiella Infections/*drug therapy ; Klebsiella pneumoniae/*drug effects/isolation &amp; purification ; Microbial Sensitivity Tests ; Postoperative Complications/*drug therapy ; }, abstract = {The purpose of this report was to determine the frequency of colonization and bacteremia with ceftazidime-resistant Klebsiella pneumoniae among pediatric candidates for and recipients of liver (LTx) and/or intestinal (ITx) transplantation. Between January and December 1994, surveillance stool cultures obtained from 51 children on the abdominal transplant service were planted on a selective medium containing 2 microg/ml of ceftazidime. Isolates of K. pneumoniae which grew on the selective medium were screened for extended-spectrum beta-lactamase (ESBL) production by the double-disk synergy test and underwent microdilutional susceptibility testing. Strain relatedness of ceftazidime-resistant K. pneumoniae was analyzed by field inversion gel electrophoresis (FIGE). Sixteen of 51 patients had > or = 1 positive stool cultures for ceftazidime-resistant K. pneumoniae; 9 out of 16 on the first culture obtained 1-23 days (median = 5) after admission. All 9 had been in hospital prior to this admission. Four others were positive on their first culture but were in our hospital for > 1 month at the onset of the study. Three patients became colonized after admission. Colonization with ceftazidime-resistant K. pneumoniae was more frequent among recipients of ITx (including combined LTx-ITx) compared to LTx alone (7/13 vs. 7/32, p<0.05). All of the ceftazidime-resistant isolates recovered from surveillance stool cultures had positive double-disk diffusion tests suggesting the presence of ESBL production as the mechanism of resistance. Ceftazidime resistance was identified in 7/8 episodes of bacteremia due to K. pneumoniae in patients on the abdominal transplant service compared with 0/17 episodes in other children in the Children's Hospital of Pittsburgh during the study. During this same time period, 69/312 clinical isolates of K. pneumoniae evaluated in the hospital laboratory were ceftazidime-resistant; 67/69 came from patients on this service. In none of the 312 isolates was resistance to cefotaxime found in the absence of ceftazidime resistance. Unique clones were identified for 10/19 isolates of ceftazidime-resistant strains of K. pneumoniae analyzed by FIGE. Colonization and bacteremia with ceftazidime-resistant K. pneumoniae were commonly identified among recipients of LTx &amp; ITx at the Children's Hospital of Pittsburgh. The mechanism of resistance appeared to be due to the presence of ESBL production by resistant strains. Although resistant strains were frequently recovered from patients on the abdominal transplant service, recovery of ceftazidime-resistant strains from patients outside of this service was rare even in the intensive care setting.}, }
@article {pmid10074541, year = {1999}, author = {Richter, S and Cormican, MG and Pfaller, MA and Lee, CK and Gingrich, R and Rinaldi, MG and Sutton, DA}, title = {Fatal disseminated Trichoderma longibrachiatum infection in an adult bone marrow transplant patient: species identification and review of the literature.}, journal = {Journal of clinical microbiology}, volume = {37}, number = {4}, pages = {1154-1160}, pmid = {10074541}, issn = {0095-1137}, mesh = {Adult ; Antifungal Agents/pharmacology ; Bone Marrow Transplantation/*adverse effects ; Drug Resistance, Microbial ; Fatal Outcome ; Feces/microbiology ; Humans ; Immunocompromised Host ; Leukemia-Lymphoma, Adult T-Cell/therapy ; Male ; Mycoses/*etiology/*microbiology ; Opportunistic Infections/etiology/microbiology ; Trichoderma/drug effects/*isolation &amp; purification/*pathogenicity ; }, abstract = {Trichoderma longibrachiatum was recovered from stool surveillance cultures and a perirectal ulcer biopsy specimen from a 29-year-old male who had received an allogeneic bone marrow transplant for acute lymphoblastic leukemia. The amphotericin B (2.0 microgram/ml) and itraconazole (1.0 microgram/ml) MICs for the organism were elevated. Therapy with these agents was unsuccessful, and the patient died on day 58 posttransplantation. At autopsy, histologic sections from the lungs, liver, brain, and intestinal wall showed infiltration by branching septate hyphae. Cultures were positive for Trichoderma longibrachiatum. While Trichoderma species have been recognized to be pathogenic in profoundly immunosuppressed hosts with increasing frequency, this is the first report of probable acquisition through the gastrointestinal tract. Salient features regarding the identification of molds in the Trichoderma longibrachiatum species aggregate are presented.}, }
@article {pmid10071980, year = {1999}, author = {Tatsuta, N and Suzuki, N and Mochizuki, T and Koya, K and Kawakami, M and Shishido, T and Motoji, N and Kuroiwa, H and Shigematsu, A and Chen, LB}, title = {Pharmacokinetic analysis and antitumor efficacy of MKT-077, a novel antitumor agent.}, journal = {Cancer chemotherapy and pharmacology}, volume = {43}, number = {4}, pages = {295-301}, doi = {10.1007/s002800050898}, pmid = {10071980}, issn = {0344-5704}, mesh = {Animals ; Antineoplastic Agents/blood/*pharmacokinetics/*therapeutic use ; Autoradiography ; Carbon Radioisotopes ; Chromatography, High Pressure Liquid ; Colonic Neoplasms/blood/*drug therapy ; Female ; Half-Life ; Humans ; Male ; Metabolic Clearance Rate ; Mice ; Mice, Nude ; Pyridines/blood/*pharmacokinetics/*therapeutic use ; Thiazoles/blood/*pharmacokinetics/*therapeutic use ; Tissue Distribution ; Transplantation, Heterologous ; }, abstract = {MKT-077 (1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4- oxothiazolidin-2-ylidenemethyl] pyridinium chloride), a novel rhodacyanine dye in phase I/II clinical trials, may provide a new approach to cancer therapy based on the accumulation in the mitochondria of the cells of certain carcinomas, for example, those of the colon, breast and pancreas. To support the development of MKT-077 for clinical application as an intravenous (i.v.) therapy, we investigated the metabolic fate of [14C]MKT-077 in BDF1 mice as well as the distribution of MKT-077 in experimental LS174T tumor-bearing mice using a high-performance liquid chromatography (HPLC) method. The plasma levels of 14C after i.v. administration of [14C]MKT-077 declined in a triphasic manner. In the first distribution phase, the levels of 14C decreased with a T1/2 of approximately 5 min. In the second and terminal phase, the T1/2 of 14C was 2.8-4.6 h and 16.2 h, respectively. Cmax (1 min after injection) increased from 0.3 to 1.5 microg/ml linearly, but less than proportionately between the doses. The AUC(0-infinity) at 0.3, 1 and 3 mg/kg were 0.030 +/- 0.002, 0.60 +/- 0.12 and 1.73 +/- 0.25 microg x h/ml, respectively. Plasma clearance was approximately 1.8 l/h per kg (at doses of 1 and 3 mg/kg). The steady state volume of distribution (6.8 and 25.1 l/kg) indicated that MKT-077 distributed as a lipid-soluble molecule. The mean residence time (MRT) was 4.1 (at a dose of 1 mg/kg) and 14.1 h (at a dose of 3 mg/kg). In the first rapid phase (5 min after dosing), 14C radioactivity was detected in most of the tissues and organs, most strongly in the kidney cortex, and not in the central nervous system and testes. In the terminal phase (24 h after dosing), 14C contents increased in the intestinal tract, and in the kidney and liver were nearly to the background level. After i.v. bolus administration at a dose of 3 mg/kg of [14C]MKT-077, the predominant route of elimination of the radioactivity was via the feces, and recoveries of total radioactivity in urine and feces corresponded to 33.5% and 61.1%, respectively. More than 60% was recovered within 24 h and 95% within 1 week. MKT-077 was primarily excreted in unmetabolized form with five unidentified metabolites found in the urine and plasma. Intact MKT-077 was retained in the tumor tissue longer than in plasma and kidney in LS174T tumor-bearing mice receiving MKT-077 at an i.v. therapeutic dose (10 mg/kg). This accumulation decreased very slowly, suggesting that the high membrane potentials of tumor cell mitochondria may help retain the drug in tumors.}, }
@article {pmid10050944, year = {1998}, author = {Cavallaro, A and Fellner, F and Matzel, KE and Stadelmaier, U and Rupprecht, T and Böwing, B and Hohenberger, W and Bautz, W}, title = {Low-field magnetic resonance imaging of the pelvis in patients with anal dynamic graciloplasty: initial experience.}, journal = {Magma (New York, N.Y.)}, volume = {7}, number = {3}, pages = {179-183}, pmid = {10050944}, issn = {0968-5243}, mesh = {Adult ; Anal Canal/*surgery ; Echo-Planar Imaging/*methods ; Electric Stimulation ; Electrodes, Implanted ; Fecal Incontinence/diagnosis/*surgery ; Female ; Humans ; Muscle, Skeletal/transplantation ; Pelvis/anatomy &amp; histology ; Postoperative Complications/*diagnosis ; Surgical Flaps ; }, abstract = {The aim of this study was to determine whether low-field magnetic resonance (MR) imaging can safely and accurately depict inflammatory changes in patients with anal dynamic graciloplasty, in whom high-field MR imaging is contraindicated and ultrasonography and computed tomography are inadequate. A 0.2-T field-strength MR examination was performed in six patients with anal dynamic graciloplasty malfunction in whom reoperation was contemplated. The following sequences were applied: T2-weighted turbo spinecho with fat saturation, T1-weighted conventional spin-echo, and contrast-enhanced T1-weighted conventional spin-echo with fat saturation. Results indicated that none of the patients experienced relevant discomfort, pacemaker malfunction, or electrode dislocation with low-field MR imaging. Inflammatory pelvic changes were visualized in four patients and atrophy of the transposed gracilis muscle in another. Surgery was thus avoided in the four, who underwent conservative treatment for their pelvic inflammation. It was concluded that these preliminary results demonstrate the feasibility of MR imaging with a low field strength in patients with anal dynamic graciloplasty. In such patients, in whom diagnostic imaging had been problematic, the potential for safe and accurate visualization will be a boon to treatment planning.}, }
@article {pmid10030299, year = {1999}, author = {Gumbo, T and Hobbs, RE and Carlyn, C and Hall, G and Isada, CM}, title = {Microsporidia infection in transplant patients.}, journal = {Transplantation}, volume = {67}, number = {3}, pages = {482-484}, doi = {10.1097/00007890-199902150-00024}, pmid = {10030299}, issn = {0041-1337}, mesh = {Animals ; Anti-Infective Agents/therapeutic use ; Cyclosporine/therapeutic use ; Diarrhea/etiology/parasitology ; Feces/parasitology ; Graft Rejection/drug therapy ; *Heart Transplantation/immunology ; Humans ; Immunosuppressive Agents/therapeutic use ; MEDLINE ; Male ; Metronidazole/therapeutic use ; *Microsporida/isolation &amp; purification ; Microsporidiosis/*diagnosis/drug therapy ; Middle Aged ; Postoperative Complications ; }, abstract = {BACKGROUND: Microsporidia are the most common cause of chronic diarrhea in patients infected with human immunodeficiency virus. Patients who have undergone organ transplantation may also be infected. The precise immune defect and the clinical picture in transplant patients have not been studied.<br><br>METHODS: We report a case of microsporidia infection in a heart transplant patient and review three other cases reported in the literature.<br><br>RESULTS: Infection in three solid organ transplant patients occurred when the patients were receiving immunosuppressive therapy for rejection 1.5-3 years after transplantation. Patients had chronic diarrhea, vomiting, dyspepsia, and weight loss for 1 month to 3 years.<br><br>CONCLUSIONS: Microsporidia may be the cause of chronic unexplained diarrhea and gastrointestinal disturbances in transplant patients. Defects in cell-mediated immunity probably play a role in maintaining the chronicity of this infection. Specific screening requests should be made to the microbiology laboratory when microsporidia infection is suspected.}, }
@article {pmid10029613, year = {1999}, author = {Madoff, RD and Rosen, HR and Baeten, CG and LaFontaine, LJ and Cavina, E and Devesa, M and Rouanet, P and Christiansen, J and Faucheron, JL and Isbister, W and Köhler, L and Guelinckx, PJ and Påhlman, L}, title = {Safety and efficacy of dynamic muscle plasty for anal incontinence: lessons from a prospective, multicenter trial.}, journal = {Gastroenterology}, volume = {116}, number = {3}, pages = {549-556}, doi = {10.1016/s0016-5085(99)70176-9}, pmid = {10029613}, issn = {0016-5085}, mesh = {Adolescent ; Adult ; Aged ; Electric Stimulation ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/physiopathology/surgery/*transplantation ; Pain, Postoperative ; Postoperative Complications/epidemiology ; Prospective Studies ; *Surgical Flaps/adverse effects ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Dynamic muscle plasty has been advocated as therapy for refractory fecal incontinence and for anorectal reconstruction to avoid colostomy after abdominoperineal resection. This study evaluates the results of a multicenter experience with dynamic muscle plasty in the treatment of fecal incontinence and total anal reconstruction.<br><br>METHODS: One hundred thirty-nine patients were enrolled at 12 centers between June 1992 and November 1994 and followed up through June 1996. Intramuscular leads and neurostimulators were implanted to stimulate transposed gracilis or gluteus muscle. Success was defined as 70% reduction in solid stool incontinence for patients with baseline incontinence and zero incontinence to solid stool for patients with baseline stomas and for patients undergoing total anal reconstruction.<br><br>RESULTS: Overall, 85 of 128 graciloplasty patients (66%) achieved and maintained a successful outcome over the follow-up period. By etiology, these proportions were 71%, 50%, and 66% for patients with acquired fecal incontinence, congenital incontinence, and total anal reconstruction, respectively. One third of graciloplasty patients experienced a major wound complication, with therapy failing in 41%. Experienced centers had better outcomes and lower complication rates than inexperienced centers. Of the 11 gluteoplasty patients, 5 (45%) achieved and maintained a successful outcome.<br><br>CONCLUSIONS: Dynamic graciloplasty may be an effective procedure for patients with refractory, end-stage fecal incontinence as well as for patients who require anorectal excision for low-lying malignancy. However, the procedure has significant morbidity that can lead to functional failure. Outcome after dynamic graciloplasty appears to correlate with surgical experience. In contrast to graciloplasty, the use of dynamic gluteoplasty should be limited to investigational purposes.}, }
@article {pmid10027361, year = {1999}, author = {Sielezneff, I and Malouf, AJ and Bartolo, DC and Pryde, A and Douglas, S}, title = {Dynamic graciloplasty in the treatment of patients with faecal incontinence.}, journal = {The British journal of surgery}, volume = {86}, number = {1}, pages = {61-65}, doi = {10.1046/j.1365-2168.1999.00936.x}, pmid = {10027361}, issn = {0007-1323}, mesh = {Adult ; Electric Stimulation/instrumentation ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Intraoperative Complications/etiology ; Male ; Middle Aged ; Muscle, Smooth/*transplantation ; Postoperative Complications/etiology ; Pressure ; Prospective Studies ; Prostheses and Implants ; }, abstract = {BACKGROUND: Dynamic graciloplasty is a recent innovation in the surgical management of faecal incontinence. This study reports further experience with this procedure in a series of consecutive patients.<br><br>METHODS: Between July 1994 and February 1998, 21 dynamic graciloplasties were performed in 18 patients with total faecal incontinence. The two most recent patients were excluded because of follow-up less than 6 months. Continence scores and manometric data were collected before operation and 6 months afterwards. Subsequent clinical data were obtained at regular outpatient review. Seven patients had a three-stage procedure (vascular delay and stoma creation; gracilis transposition and implantation of stimulator and leads; stoma closure), four patients had a two-stage procedure (stoma, with transposition and implantation; stoma closure) and five underwent a one-stage procedure without defunctioning stoma.<br><br>RESULTS: Mean(s.d.) follow-up was 20(10.2) months, and was complete in all patients. Eight of the 16 patients had postoperative morbidity. Thirty-three subsequent admissions and 23 reoperations were required to treat complications, to correct technical problems or to manage outcome failures. A defunctioning stoma did not protect wounds from infection (P = 0.6) or reduce the postoperative morbidity rate (P = 0.14). Continence scores were improved by the procedure (P < 0.001) and anal canal pressure increased with stimulation (mean increase 35.9 cmHO, P < 0.001). Two patients required revisional surgery for perielectrode fibrosis. Five patients had revisional surgery for electrical device failure. Thirteen of the 16 patients were either improved or fully continent after operation, and satisfied with the result of the procedure. Ultimate failure (n = 3) occurred in patients with chronic preoperative constipation or diarrhoea, or abnormal rectal sensitivity.<br><br>CONCLUSION: Dynamic graciloplasty is an effective procedure in selected cases of end-stage faecal incontinence. Patient motivation is essential given the necessity for close follow-up.}, }
@article {pmid10075604, year = {1999}, author = {Kaplan, B and Lown, K and Craig, R and Abecassis, M and Kaufman, D and Leventhal, J and Stuart, F and Meier-Kriesche, HU and Fryer, J}, title = {Low bioavailability of cyclosporine microemulsion and tacrolimus in a small bowel transplant recipient: possible relationship to intestinal P-glycoprotein activity.}, journal = {Transplantation}, volume = {67}, number = {2}, pages = {333-335}, doi = {10.1097/00007890-199901270-00026}, pmid = {10075604}, issn = {0041-1337}, mesh = {Biological Availability ; Chemistry, Pharmaceutical ; Cyclosporine/*pharmacokinetics/therapeutic use ; Emulsions ; Female ; Humans ; Immunosuppressive Agents/*pharmacokinetics/therapeutic use ; *Intestinal Absorption ; Intestinal Pseudo-Obstruction/surgery ; Intestine, Small/physiology/*surgery ; Middle Aged ; Tacrolimus/*pharmacokinetics/therapeutic use ; Transplantation, Homologous/immunology/*physiology ; }, abstract = {With intestine transplants the allograft is dependent on itself for maintenance of adequate immunosuppression. We evaluated an intestinal transplant recipient who required very large doses of either tacrolimus or cyclosporine emulsion to achieve acceptable blood concentrations. Pharmacokinetic studies revealed bioavailabilities of 2% and 6% respectively, while D-xylose and B12 absorption were found to be within normal limits and fecal fat was only slightly increased, suggesting that there was a selective absorptive defect for these drugs. Biopsies of the allograft ileum revealed a high P-glycoprotein activity compared to the jejunum or to intestinal biopsies from other normal subjects. This may be a contributing factor to poor immunosuppressive drug absorption in this patient and others.}, }
@article {pmid9931665, year = {1998}, author = {Köhler, A and Ommer, A and Athanasiadis, S}, title = {[Dynamic gracilis-plasty as final therapeutic possibility in anorectal incontinence].}, journal = {Langenbecks Archiv fur Chirurgie. Supplement. Kongressband. Deutsche Gesellschaft fur Chirurgie. Kongress}, volume = {115}, number = {}, pages = {488-493}, pmid = {9931665}, issn = {0942-2854}, mesh = {Adult ; Aged ; Anal Canal/surgery ; Fecal Incontinence/etiology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Postoperative Complications/etiology ; Reoperation ; Treatment Outcome ; }, abstract = {UNLABELLED: Six patients (five women, one man with an average age of 63 years) underwent a dynamic graciloplasty. Three patients had a three- or two-stage procedure; the past three patients were treated by a one-stage procedure without any negative consequences. None of the patients received a protective stoma.<br><br>COMPLICATIONS: COMPLICATIONS, needing surgical intervention occurred in two patients. In one of these patients a positive final result may still fail.<br><br>RESULTS: Five patients are subjectively continent and satisfied. Four are able to retain a clysma without any problem. As a result of stimulation, three patients developed optimal anal pressures. In two patients the pressure values are satisfactory. Three patients developed evacuation problems, which up to now have been managed by laxatives.<br><br>CONCLUSION: The dynamic graciloplasty is a new hope for carefully chosen patients, in whom other methods have failed.}, }
@article {pmid9931664, year = {1998}, author = {Bruch, HP and Roblick, UJ}, title = {[Insufficiency of the anal sphincter--attempt at anorectal reconstruction].}, journal = {Langenbecks Archiv fur Chirurgie. Supplement. Kongressband. Deutsche Gesellschaft fur Chirurgie. Kongress}, volume = {115}, number = {}, pages = {482-487}, pmid = {9931664}, issn = {0942-2854}, mesh = {Anal Canal/surgery ; Fecal Incontinence/etiology/*surgery ; Female ; Humans ; Male ; Muscles/*transplantation ; *Prosthesis Implantation/instrumentation ; Treatment Outcome ; }, abstract = {Continence is highly appreciated in society and is a precondition for human socialization. Thus, in the history of surgery there have been numerous attempts to develop repair techniques for incontinence. They can roughly be divided into three groups: actively inflatable implants (plastic prosthesis), transfer of smooth muscles or transfer of striated, conditioned muscles. In the majority of cases these techniques may well prevent the strains associated with colostomy; however, the patients will remain incapable of recognizing and discriminating the cue of rectal distension. Consequently, repair of sphincter defects will continue to be of major concern in surgery.}, }
@article {pmid9922503, year = {1998}, author = {Sobrado, CW and Nahas, SC and da Silva e Souza Júnior, AH and Habr-Gama, A}, title = {[Muscle-aponeurotic transposition for treatment of anal incontinence].}, journal = {Revista do Hospital das Clinicas}, volume = {53}, number = {4}, pages = {205-213}, pmid = {9922503}, issn = {0041-8781}, mesh = {Anal Canal/injuries/surgery ; Digestive System Surgical Procedures/methods ; Fecal Incontinence/*surgery ; Humans ; Muscle, Skeletal/*transplantation ; *Surgical Flaps ; Suture Techniques/standards ; }, abstract = {The management of anal incontinence varies. It can be treated either clinically or surgically depending on its etiology and the intensity of the signs and symptoms. The variety of procedures and techniques employed in its treatment is proof of the incomprehension of the pathophysiological mechanisms involved as well as their diversity. Sphincteroplasties are indicated for those patients with well-defined muscle injury, usually resulting from obstetrical trauma, iatrogenic surgery or vehicular accidents. In cases of persistent anal incontinence after previous sphincteroplasty or those in which extensive destruction of the sphincteric musculature is confirmed, muscle-aponeurotic transpositions are an attractive option. A detailed survey of the literature of the chief techniques utilized and their results is presented.}, }
@article {pmid9877276, year = {1998}, author = {Ghosh, K and Ayyaril, M and Nirmala, V}, title = {Acute GVHD involving the gastrointestinal tract and infestation with Blastocystis hominis in a patient with chronic myeloid leukaemia following allogeneic bone marrow transplantation.}, journal = {Bone marrow transplantation}, volume = {22}, number = {11}, pages = {1115-1117}, doi = {10.1038/sj.bmt.1701488}, pmid = {9877276}, issn = {0268-3369}, mesh = {Acute Disease ; Adult ; Animals ; Antiprotozoal Agents/therapeutic use ; Blastocystis Infections/drug therapy/*etiology ; *Blastocystis hominis/isolation &amp; purification/pathogenicity ; Bone Marrow Transplantation/*adverse effects ; Feces/parasitology ; Female ; Gastrointestinal Diseases/*etiology/pathology ; Graft vs Host Disease/*etiology/pathology ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*therapy ; Metronidazole/therapeutic use ; Rectum/pathology ; Transplantation, Homologous ; }, abstract = {A 21-year-old female underwent allogeneic bone marrow transplantation (ABMT) from her HLA matched brother for chronic myeloid leukaemia in the chronic phase. Four weeks post transplant she developed tenesmus, mucoid stool mixed with blood and lower abdominal pain. This rapidly progressed to greenish watery diarrhoea with flakes of mucous membrane floating in it, conforming to the classical clinical description of acute GVHD of the bowel. Stool microscopy showed profuse numbers of Blastocystis hominis, a parasite with doubtful pathogenicity in an immunocompetent host. In the present case the parasite played a pathogenic role as evidenced by the profuse number in the stool sample, focal neutrophil infiltration of the rectal mucosa, initial presentation of the patient with dysentery, and requirement for prolonged metronidazole therapy to eradicate the parasite and cure the diarrhoea. She also had grade I GVHD of the liver and skin. In developing tropical countries, hitherto unreported parasitic infestations may complicate the picture of acute GVHD.}, }
@article {pmid9867162, year = {1998}, author = {Suzuki, YS and Momose, Y and Higashi, N and Shigematsu, A and Park, KB and Kim, YM and Kim, JR and Ryu, JM}, title = {Biodistribution and kinetics of holmium-166-chitosan complex (DW-166HC) in rats and mice.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {39}, number = {12}, pages = {2161-2166}, pmid = {9867162}, issn = {0161-5505}, mesh = {Animals ; Autoradiography ; Chitin/*analogs &amp; derivatives/blood/pharmacokinetics/urine ; Feces ; Holmium/blood/*pharmacokinetics/urine ; Kinetics ; Male ; Metabolic Clearance Rate ; Mice ; Mice, Inbred ICR ; Mice, Nude ; Organometallic Compounds/blood/*pharmacokinetics/urine ; Radioisotopes/*pharmacokinetics ; Radiopharmaceuticals/blood/*pharmacokinetics/urine ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution ; }, abstract = {UNLABELLED: The fate of 166Ho-chitosan complex, a radiopharmaceutical drug for cancer therapy, was determined by studying its absorption, distribution and excretion in rats and mice.<br><br>METHODS: Holmium-166-chitosan complex [0.75 mg of Ho(NO3)3 x 5H2O and 1 mg chitosan/ head] was administered intrahepatically to male rats. Radioactive concentrations in blood, urinary and fecal excretion and radioactive distribution in tissues were examined. To determine the effects of chitosan in 166Ho-chitosan complex, 166Ho alone [0.75 mg of Ho(NO3)3 x 5H2O/head] was intrahepatically administered to male rats, and radioactive concentrations in blood, urinary and fecal excretion and radioactive distribution were examined. In B16 melanoma-transplanted nude mice, radioactive distribution after intratumoral administration of 166Ho-chitosan complex [0.075 mg of Ho(NO3)3 x 5H2O and 0.10 mg chitosan/head] was investigated also.<br><br>RESULTS: After administration of 166Ho-chitosan complex, the radioactive concentrations in blood were low, and cumulative urinary and fecal excretions over a period of 0-72 hr were 0.53% and 0.54%, respectively. The radioactive concentrations in tissues and the whole-body autoradiography images showed that most of the administered radioactivity was localized at the administration site, and only slight radioactivity was detected from the liver, spleen, lungs and bones. On the other hand, results of intrahepatic administration of 166Ho alone showed high radioactive concentrations in the blood, and the whole-body autoradiographs showed that the administered radioactivity was distributed in many organs and tissues. These results strongly suggest that 166Ho is retained at the administration site only when it forms a chelate complex with chitosan. Autoradiographs after intratumoral administration of 166Ho-chitosan complex showed that radioactivity was localized at the site of administration without distribution to the other organs and tissues.<br><br>CONCLUSION: Administered 166Ho-chitosan complex is retained at the administration site after either intrahepatic or intratumoral administration to rats or tumor-transplanted nude mice.}, }
@article {pmid9856254, year = {1998}, author = {Dösoğlu, M and Orakdöğen, M and Tevrüz, M and Göğüsgeren, MA and Mutlu, F}, title = {Enterocutaneous fistula: a complication of posterior iliac bone graft harvesting not previously described.}, journal = {Acta neurochirurgica}, volume = {140}, number = {10}, pages = {1089-1092}, doi = {10.1007/s007010050219}, pmid = {9856254}, issn = {0001-6268}, mesh = {Aged ; *Bone Transplantation ; Cervical Vertebrae/surgery ; Colonic Diseases/*diagnostic imaging ; Cutaneous Fistula/*diagnostic imaging ; Humans ; Ilium/*surgery ; Intestinal Fistula/*diagnostic imaging ; Male ; Postoperative Complications/*diagnostic imaging ; Radiography ; *Spinal Fusion ; Spondylolisthesis/surgery ; Transplantation, Autologous ; }, abstract = {A case of enterocutaneous fistula at the donor site is presented. A patient underwent posterior C5-C6 wire fusion with autologous bone graft taken from the posterior superior iliac crest for degenerative C5-C6 spondylolisthesis. The tip of the osteotome slipped anteriorly during the procurement but neither neurovascular nor peritoneal injury were observed. Spillage of formed faecal material was observed from the donor site on the 12th postoperative day. Fistulogram showed an enterocutaneous fistula to descending colon. The fistula closed spontaneously in a week. Enterocutaneous fistula after bone harvesting has never been reported in the literature as far as we know. Congenital malformations and acquired causes may create a vulnerable peritoneal area. Small bowel or descending colon may show a close relationship or even an adhesion to peritoneum in the presence of local peritonitis. A small lesion in this area may play a role in the occurrence of a fistula, and a low flow pseudofistulous tract may appear. The thermal injury and possible ischaemic necrosis due to cauterisation may be predisposing factors in the aetiology of this kind of fistula. The lack of foreign material and spontaneous closure were against an infectious origin. The aims of this report are to present and analyse the reasons of this complication, not previously described.}, }
@article {pmid9854103, year = {1999}, author = {Möller, LV and Arends, JP and Harmsen, HJ and Talens, A and Terpstra, P and Slooff, MJ}, title = {Ochrobactrum intermedium infection after liver transplantation.}, journal = {Journal of clinical microbiology}, volume = {37}, number = {1}, pages = {241-244}, pmid = {9854103}, issn = {0095-1137}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteremia/complications/drug therapy/microbiology ; DNA, Bacterial/analysis ; Female ; Gram-Negative Bacterial Infections/*etiology/microbiology ; Humans ; Immunocompromised Host ; Liver Abscess/complications ; Liver Transplantation/*adverse effects ; Microbial Sensitivity Tests ; Middle Aged ; Opportunistic Infections/microbiology ; Phylogeny ; RNA, Ribosomal, 16S/analysis ; *Rhizobiaceae/classification/drug effects/genetics/isolation &amp; purification ; }, abstract = {A case of bacteremia due to Ochrobactrum intermedium, with concomitant liver abscesses, in an orthotopic liver transplant recipient is presented. Identical microorganisms were isolated from fecal specimens and from an aspirate of a liver abscess that was indicative of invasion of the graft by gastrointestinal spread. 16S DNA sequence analysis of the blood isolate revealed the recovery of the recently proposed new species O. intermedium, closely related to Ochrobactrum anthropi and Brucella spp.}, }
@article {pmid9845639, year = {1998}, author = {Demetriades, C and Botsios, D and Tsalis, K and Manafis, K and Zisiadis, A and Dadoukis, J}, title = {Management of large rectal wall defects with open pedicle grafts of small intestine. An experimental study.}, journal = {Digestive surgery}, volume = {15}, number = {6}, pages = {693-696}, doi = {10.1159/000018680}, pmid = {9845639}, issn = {0253-4886}, mesh = {Animals ; Disease Models, Animal ; Dogs ; Female ; Follow-Up Studies ; Graft Survival ; Intestinal Mucosa/pathology ; Intestine, Small/*transplantation ; Male ; Rectum/injuries/*surgery ; Suture Techniques ; Tissue Transplantation/*methods ; Wound Healing/physiology ; }, abstract = {The aim of this study was to evaluate the possible repair of large rectal wall defects using an open pedicle ileal graft as a mucosal patch. This experiment was carried out in 14 adult mongrel dogs. By excision of a portion of the antimesenteric wall comprising 50-70% of the circumference and measuring 5-6 cm in length, a suitable full thickness defect was created in the lower part of the rectum. A segment of the distal ileum was then isolated on a mesenteric pedicle and opened from its antimesenteric border. This was sutured over the defect in two layers. The animals were observed for a period of 15 days to 12 months. All the animals survived the operation apart from 1 dog that died of fecal peritonitis. Function of the rectum generally remained normal. Barium X-ray did not show any obstruction, shrinkage of the patch, lumen dilatation or extravasation. At the time of autopsy pedicles of ileal grafts appeared intact and pulsating. On gross examination there was no evidence of focal hemorrhage, ulceration or any cicatricial thickening of the grafts. Healing was good and the ileal mucosa retained its villi and general characteristics without any major inflammatory reactions. There was an increase in the number of goblet cells which returned to normal in 6 months.}, }
@article {pmid9815598, year = {1997}, author = {Raynaud, FI and Boxall, FE and Goddard, PM and Valenti, M and Jones, M and Murrer, BA and Abrams, M and Kelland, LR}, title = {cis-Amminedichloro(2-methylpyridine) platinum(II) (AMD473), a novel sterically hindered platinum complex: in vivo activity, toxicology, and pharmacokinetics in mice.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {3}, number = {11}, pages = {2063-2074}, pmid = {9815598}, issn = {1078-0432}, mesh = {Animals ; Antineoplastic Agents/pharmacokinetics/*therapeutic use/toxicity ; Carboplatin/toxicity ; Cisplatin/toxicity ; Drug Resistance, Neoplasm ; Female ; Half-Life ; Humans ; Kinetics ; Leukemia L1210/*drug therapy ; Metabolic Clearance Rate ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Organoplatinum Compounds/pharmacokinetics/*therapeutic use/toxicity ; Ovarian Neoplasms/*drug therapy ; Plasmacytoma/*drug therapy ; Tissue Distribution ; Transplantation, Heterologous ; Tumor Cells, Cultured ; }, abstract = {A novel sterically hindered platinum complex, AMD473 [cis-amminedichloro(2-methylpyridine) platinum(II)], designed primarily to be less susceptible to inactivation by thiols, has shown in vitro activity against several ovarian carcinoma cell lines. Notably, AMD473 has shown activity in vitro in human carcinoma cells that have acquired cisplatin resistance due to reduced drug transport (41M/41McisR) or enhanced DNA repair/increased tolerance of platinum-DNA adducts (CH1/CH1cisR). In this study, we show that AMD473, at its maximum tolerated dose of 35-40 mg/kg i.p. administration, produced marked in vivo antitumor activity against a variety of murine (ADJ/PC6 plasmacytoma, L1210 leukemia) and human ovarian carcinoma xenograft models, including several possessing acquired resistance to cisplatin [ADJ/PC6cisR, L1210cisR, CH1cisR, and HX110 (carboplatin-resistant)]. In the ADJ/PC6 model, an increased therapeutic index was noted following oral as opposed to i. p. administration. In a head-to-head comparison using CH1cisR xenografts and equitoxic doses (q7dx4 schedule), comparative growth delays were as follows: AMD473, 34 days; cisplatin, 10.4 days; carboplatin, 6.4 days; and JM216 (p.o. administration), 3.5 days (in a previous experiment, the trans-platinum complex JM335 induced a growth delay of 5.4 days against this model). In this model, oral activity was also noted with a growth delay of 34 days at 400 mg/kg every 7 days (total of four doses). In addition, AMD473 showed promising activity against CH1 xenografts that had regrown following initial treatment with cisplatin (additional growth delay of 30 days over that observed for retreatment with cisplatin). Across the whole panel of cisplatin-sensitive to cisplatin-resistant human ovarian carcinoma xenografts, AMD473 showed improved or at least comparable activity to that observed for an equitoxic dose (4 mg/kg) and schedule of cisplatin. Platinum pharmacokinetics showed that following i.v. administration of 20 mg/kg AMD473 in saline to Balb/c- mice bearing murine plasmacytoma (ADJ/PC6), a biexponential decay was observed in the plasma with a rapid distribution t1/2alpha of 24 min followed by a slow elimination t1/2beta of 44 h. Platinum accumulated in various organs with platinum tissue to plasma area under the curve ratios of 8.6 for liver and kidney, 5.7 for spleen, 3.7 for heart, 5.2 for lung, and 5 for tumor. The plasma and tissue concentration time curve following i.p. administration was similar to that observed following i.v. administration, with a bioavailability of 89%. When AMD473 was given p.o., the platinum absorption was rapid (K01 of 30 min) and the bioavailability was 40%. A less than proportional increase in area under the curve and Cmax was noted in tissue, plasma, and plasma ultrafiltrate following increasing oral doses of AMD473. In vitro, with AMD473, the rate of binding to different plasma proteins was approximately half of that of cisplatin. Following administration of 45 mg/kg i.p. in oil, 33% of the administered platinum was eliminated in the urine after 24 h, and 40% was eliminated after 72 h. Fecal recovery represented 13% of the administered dose after 3 days. Similar results were observed following oral and i.v. administration of 20 mg/kg, but significantly more was excreted in the feces (over 50% of the administered dose) following oral administration of 400 mg/kg, showing that absorption might be a limiting factor by this route of administration. The dose-limiting toxicity for AMD473 in mice was myelosuppression, and no renal toxicity was observed. The promising antitumor activity of AMD473, together with its lack of nephrotoxicity and favorable pharmacokinetic profile, suggests that AMD473 is a good candidate for clinical development. AMD473 is entering Phase I clinical trials under the auspices of the United Kingdom Cancer Research Campaign in 1997.}, }
@article {pmid9778138, year = {1998}, author = {Kawasaki, M and Funabiki, R and Yagasaki, K}, title = {Effects of dietary methionine and cystine on lipid metabolism in hepatoma-bearing rats with hyperlipidemia.}, journal = {Lipids}, volume = {33}, number = {9}, pages = {905-911}, pmid = {9778138}, issn = {0024-4201}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Body Weight/drug effects ; Carcinoma, Hepatocellular/complications/drug therapy/*metabolism ; Cholesterol/blood ; Cystine/*pharmacology ; Diet ; Eating ; Feces ; Hyperlipidemias/drug therapy/*metabolism ; Lipase/drug effects/metabolism ; *Lipid Metabolism ; Lipids/blood ; Lipoprotein Lipase/drug effects/metabolism ; Liver/drug effects/metabolism ; Male ; Methionine/*pharmacology ; Neoplasm Transplantation ; Rats ; Sterol Esterase/drug effects/metabolism ; Triglycerides/blood ; }, abstract = {Abnormal lipid metabolism and its restoration by dietary methionine (Met) and cystine (Cys) were studied in Donryu rats subcutaneously implanted with an ascites hepatoma cell line of AH109A. The hepatoma-bearing rats exhibited hyperlipidemia characterized by rises in serum triglyceride and cholesterol levels. Decreased lipoprotein lipase (LPL) activities in epididymal adipose tissue, cardiac muscle, and gastrocnemius as well as increased fatty acid mobilization from adipose tissue were considered to be responsible for the hepatoma-induced hypertriglyceridemia, while increased hepatic cholesterogenesis and decreased steroid excretion into feces were thought to be responsible for the hepatoma-induced hypercholesterolemia. Dietary-supplemented Met or Cys reduced the AH109A-induced hypertriglyceridemia with suppression of fatty acid synthesis in the host liver. Met restored the fall of LPL activities, while Cys did not. Dietary Met or Cys also reduced the hypercholesterolemia with restoration of decreased bile acid excretion into feces. These results suggest that dietary Met or Cys is hypolipidemic in the hepatoma-bearing rats with slight differences in their modes of action.}, }
@article {pmid9774022, year = {1998}, author = {Bernardi, C and Favetta, U and Pescatori, M}, title = {Autologous fat injection for treatment of fecal incontinence: manometric and echographic assessment.}, journal = {Plastic and reconstructive surgery}, volume = {102}, number = {5}, pages = {1626-1628}, doi = {10.1097/00006534-199810000-00046}, pmid = {9774022}, issn = {0032-1052}, mesh = {Adipose Tissue/*transplantation ; Adult ; Fecal Incontinence/diagnostic imaging/*surgery ; Female ; Humans ; Manometry ; Transplantation, Autologous ; Ultrasonography ; }, }
@article {pmid9769870, year = {1998}, author = {Barbé, G and Ploton, C and Pondarré, C and Bertrand, Y and Souillet, G and Philippe, N}, title = {[Vancomycin-resistant enterococci in pediatric hematology: don't panic!].}, journal = {Pathologie-biologie}, volume = {46}, number = {6}, pages = {408-411}, pmid = {9769870}, issn = {0369-8114}, mesh = {Amikacin/therapeutic use ; Anemia, Aplastic/complications/therapy ; Antineoplastic Agents/therapeutic use ; Bone Marrow Transplantation ; Carrier State ; Catheterization, Central Venous/adverse effects ; Child ; Decontamination ; *Drug Resistance, Microbial ; Drug Therapy, Combination/therapeutic use ; Enterococcus/*drug effects/isolation &amp; purification ; Equipment Contamination ; Feces/microbiology ; France/epidemiology ; Gram-Positive Bacterial Infections/epidemiology/*microbiology ; Hematologic Neoplasms/complications/therapy ; Home Nursing ; Hospitalization ; Humans ; Hygiene ; Imipenem/therapeutic use ; Immunocompromised Host ; Mouth/microbiology ; Mouthwashes/administration &amp; dosage ; Piperacillin/therapeutic use ; Premedication ; Prospective Studies ; Transplantation Conditioning/adverse effects ; Vancomycin/administration &amp; dosage/*pharmacology/therapeutic use ; }, abstract = {Do immunocompromised children, carrying vancomycin-resistant enterococci (VRE) need to be treated? For 3 years, 230 children with chemotherapy and/or bone-marrow transplantation (BMT) received amikacin for gut decontamination and rinsed their mouth with solutions including vancomycin or not, according to the duration and severity of neutropenia. Some patients were isolated, others were at home with ambulatory treatment. The first-line antibio-therapy was piperacillin-amikacin-vancomycin in the chemotherapy unit, imipenem-vancomycin in the BMT unit. Once-a-week, the laboratory used to check the efficiency of decontamination procedures and look for emerging resistant bacteria. Four patients were identified as VRE carriers in their gut flora. The fecal carriage was long-lasting in a single patient, for whom attempts of eradication failed. No patient underwent VRE bacteremia. From our experience, it seems reasonable to neglect enterococcal eradication, provided that hygienic measures are strictly applied.}, }
@article {pmid9769867, year = {1998}, author = {Honderlick, P and Cahen, P}, title = {[Systematic detection of toxigenic strains of Clostridium difficile--is it useful?].}, journal = {Pathologie-biologie}, volume = {46}, number = {6}, pages = {395-397}, pmid = {9769867}, issn = {0369-8114}, mesh = {*Bacterial Proteins ; Bacterial Toxins/*analysis ; Clostridioides difficile/classification/drug effects/*isolation &amp; purification/metabolism ; Comorbidity ; Cross Infection/epidemiology/*microbiology ; Drug Resistance, Microbial ; Enterocolitis, Pseudomembranous/epidemiology/*microbiology ; Feces/microbiology ; HIV Infections/epidemiology ; Humans ; Immunocompromised Host ; Incidence ; Neoplasms/epidemiology ; Postoperative Complications/epidemiology/microbiology ; Risk Factors ; Transplantation ; }, abstract = {The incidence of Clostridium difficile (Cd) infection is rising and Cd in fact is now endemic in many hospitals. During the past 4 years we analyzed our data concerning diarrhea caused by Cd in our 700 beds hospital. A positive case was defined as a Cd cytotoxine positive with or without positive culture for Cd. In the present study 120 episodes of Cd associated diarrhea occurred in 102 patients. 1101 stools were cultured from 921 patients. Since 1995 we choose to systematically evaluate Cd in diarrheal stools from hospitalized patients. 120 stool were positives (102 patients), we observed a significant difference between the 2 study periods: Cd was recovered from 16.9% of stool specimen during 1993-1994 and from 9.6% since 1995. This study clearly confirm the common role of Cd in our hospitalized patients as in all positive case, Cd was the only enteropathogen isolated. We suggest the systematic investigation of Cd in hospitalized patients.}, }
@article {pmid9764598, year = {1998}, author = {Bregenholt, S and Brimnes, J and Reimann, J and Claesson, MH}, title = {Accumulation of immunoglobulin-containing cells in the gut mucosa and presence of faecal immunoglobulin in severe combined immunodeficient (scid) mice with T cell-induced inflammatory bowel disease (IBD).}, journal = {Clinical and experimental immunology}, volume = {114}, number = {1}, pages = {19-25}, pmid = {9764598}, issn = {0009-9104}, mesh = {Animals ; Colon/cytology ; Feces ; *Immunity, Mucosal ; Immunoglobulins/*metabolism ; Inflammatory Bowel Diseases/*immunology ; Intestinal Mucosa/*immunology ; Mice ; Mice, SCID ; Severe Combined Immunodeficiency/*immunology ; T-Lymphocytes/*immunology ; }, abstract = {Scid mice transplanted either with a gut wall graft or with low numbers of purified CD4+ T cells from immunocompetent syngeneic donor mice show clinical signs of IBD 3-4 months post-transplantation. The disease is mediated by mucosa-infiltrating CD4+ TCR alphabeta+ T cells. The pathology of 52 individual colon segments obtained from 20 gut wall- or CD4+ T cell-transplanted diseased scid mice was evaluated by histology and the numbers of infiltrating immunoglobulin-containing cells were determined. In particular, cells positive for IgM, IgA and non-inflammatory immunoglobulin isotypes such as IgG1 and IgG2b were found to accumulate in colon segments displaying the most severe histopathology, including inflammatory cellular infiltration, epithelial hyperplasia and ulcerative lesions. Compared with colon segments of normal C.B-17 mice, the lesional scid colon shows increased levels of cells positive for the IgG classes. Faecal extracts of the CD4+ T cell-transplanted scid mice revealed the presence of all six murine immunoglobulin isotypes. Disease progression was accompanied by an increased level of excreted IgM and IgG3 and decreased levels of IgA. It is concluded that locally secreted immunoglobulins may play an immunomodulating role in the pathological changes observed in the present model of T cell-induced inflammatory bowel disease.}, }
@article {pmid9744775, year = {1998}, author = {Wright, JE and Pardo, M and Tretyakov, A and Alperin, WL and Trites, D and Rosowsky, A}, title = {Pharmacokinetics, antifolate activity and tissue distribution of PT523 in SCC VII tumor-bearing mice.}, journal = {Cancer chemotherapy and pharmacology}, volume = {42}, number = {4}, pages = {300-306}, doi = {10.1007/s002800050821}, pmid = {9744775}, issn = {0344-5704}, support = {CA25394/CA/NCI NIH HHS/United States ; R01-CA19589/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacokinetics/pharmacology ; Area Under Curve ; Carbon Radioisotopes ; Carcinoma, Squamous Cell/*metabolism ; Folic Acid Antagonists/*pharmacokinetics/pharmacology ; Injections, Intravenous ; Isotope Labeling ; Male ; Methotrexate/pharmacokinetics/pharmacology ; Mice ; Mice, Inbred C3H ; Neoplasms, Experimental/*metabolism ; Ornithine/*analogs &amp; derivatives/chemical synthesis/pharmacokinetics/pharmacology ; Pterins/chemical synthesis/*pharmacokinetics/pharmacology ; Tetrahydrofolates/metabolism ; Tissue Distribution ; }, abstract = {PURPOSE: To monitor the pharmacokinetics of PT523 and methotrexate in C3H mice with transplanted SCC VII tumors; to compare the impact of PT523 and methotrexate on tumor and normal host 5,10-methylenetetrahydrofolate levels; and to synthesize [14C]PT523 and determine its time-dependent tissue distribution in tumor and host tissues.<br><br>METHODS: C3H mice bearing SCC VII tumors were given i.p. PT523 or methotrexate. Plasma drug levels and tumor, gut and marrow 5,10-methylenetetrahydrofolate were assayed. [14C]PT523 was synthesized and administered i.v. to tumor-bearing mice for tissue distribution analysis.<br><br>RESULTS: Areas under the curve, mean residence times, whole body clearances, apparent distribution volumes, and plasma protein binding of PT523 vs methotrexate were, respectively, 4311 vs 6472 microM x min(-1); 20 vs 16 min; 0.56 vs 0.36 ml min(-1); 532 vs 325 ml x kg(-1); and 70% vs 30%. Both PT523 and methotrexate caused time-dependent declines in 5,10-methylenetetrahydrofolate in tumor and marrow, but not in gut mucosa [corrected]. Gut levels began to recover within 4 h in the PT523-treated group only. [14C]PT523 distributed mainly into the liver, duodenum, kidneys, lungs, tumor, pancreas and muscle; less into the spleen, blood cells, heart, brain and testicles; and very little into gut [corrected. Only 35% of the dose was excreted, and 2.9-fold more in feces than urine.<br><br>CONCLUSIONS: Despite its more rapid clearance, accumulation of PT523 in extravascular tissues was greater than that of methotrexate. Consequently, less PT523 was recovered in feces and urine and its apparent volume of distribution was greater. PT523 selectively depleted 5,10-methylenetetrahydrofolate pools in tumor and, less persistently, in marrow, but spared the gut mucosa [corrected]. [14C]PT523 tissue distribution correlated with organ mass and blood supply.}, }
@article {pmid9719202, year = {1998}, author = {Redaelli, B and Bonoldi, G and Di Filippo, G and Viganò, MR and Malnati, A}, title = {Behaviour of potassium removal in different dialytic schedules.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {13 Suppl 6}, number = {}, pages = {35-38}, doi = {10.1093/ndt/13.suppl_6.35}, pmid = {9719202}, issn = {0931-0509}, mesh = {Feces/chemistry ; Hemofiltration ; Humans ; *Peritoneal Dialysis ; Potassium/analysis/blood/*metabolism/urine ; *Renal Dialysis ; Retrospective Studies ; Water/analysis ; }, }
@article {pmid9718024, year = {1998}, author = {Eccersley, AJ and Williams, NS}, title = {Dynamic graciloplasty for severe anal incontinence.}, journal = {The British journal of surgery}, volume = {85}, number = {8}, pages = {1158-1159}, pmid = {9718024}, issn = {0007-1323}, mesh = {Anal Canal ; Electric Stimulation ; Fecal Incontinence/*surgery ; Humans ; Muscle, Skeletal/*transplantation ; Patient Satisfaction ; Surgical Flaps ; Treatment Outcome ; }, }
@article {pmid9677013, year = {1998}, author = {Christiansen, J}, title = {Modern surgical treatment of anal incontinence.}, journal = {Annals of medicine}, volume = {30}, number = {3}, pages = {273-277}, doi = {10.3109/07853899809005855}, pmid = {9677013}, issn = {0785-3890}, mesh = {Anal Canal/*surgery ; Electric Stimulation Therapy ; Fecal Incontinence/*surgery/therapy ; Female ; Humans ; Male ; Muscle, Skeletal/transplantation ; Prostheses and Implants ; }, abstract = {New surgical treatment modalities have been developed for patients with anal incontinence resulting from extensive sphincter destruction and in whom standard sphincter repair has failed. These new modalities include the transposition of striated skeletal muscles combined with implantation of neurostimulators, artificial sphincters based on the same principle as artificial urinary sphincters, and direct sacral nerve stimulation. In a few reported series muscle transposition in combination with neurostimulation has given a satisfactory continence in 50-70% of the patients. The same is true for the smaller series published on artificial anal sphincters, whereas the results of sacral nerve stimulation have thus far been reported in only a few patients. The selection of patients and the performance of these procedures should be limited to few specialist centres.}, }
@article {pmid9667713, year = {1998}, author = {Duffy, MM and Regan, MC and Harrington, MG and Fitzpatrick, JM and O'Connell, PR}, title = {Metabolic substrate utilization differs in ileal faecal and urinary reservoirs.}, journal = {The British journal of surgery}, volume = {85}, number = {6}, pages = {804-808}, doi = {10.1046/j.1365-2168.1998.00719.x}, pmid = {9667713}, issn = {0007-1323}, mesh = {Butyrates/*metabolism ; Carbon Dioxide/metabolism ; Colitis, Ulcerative/metabolism/*surgery ; Colonic Neoplasms/metabolism/*surgery ; Glutamine/*metabolism ; Humans ; Ileum/metabolism/*transplantation ; Intestinal Mucosa/metabolism ; *Proctocolectomy, Restorative ; *Urinary Reservoirs, Continent ; }, abstract = {BACKGROUND: Construction of an ileal faecal or urinary reservoir profoundly alters ileal luminal ecology and availability of mucosal metabolic substrates. The aims of this study were to measure mucosal metabolic flux of butyrate and glutamine in histologically normal (control) ileum and to determine the effect of reservoir construction on metabolic fluxes in patients with ileal pouch-anal anastomosis and ileocystoplasty.<br><br>METHODS: Endoscopic biopsy samples were obtained from normal ileum (n = 10), ileum of patients with ulcerative colitis (n = 10), ileal pouch-anal anastomosis (n = 7), ileocystoplasty (n = 7) and ileal conduit (n = 7). Using a closed microculture technique, biopsy utilization of 14C-labelled butyrate and glutamine was measured as [14C]carbon dioxide production. Biopsy DNA content was measured and [14C]carbon dioxide evolution expressed as picomoles [14C]carbon dioxide per microgram DNA per hour.<br><br>RESULTS: The metabolic flux of both butyrate and glutamine was reduced in ileal pouch mucosa compared with that of ileal mucosa in patients with ulcerative colitis. In contrast, the metabolic flux of buyrate alone was reduced in ileal mucosa from ileocystoplasty and ileal conduit compared with that in normal ileal mucosa, while the metabolic flux of glutamine remained unchanged.<br><br>CONCLUSION: Ileal mucosal metabolic fluxes measured in vitro are altered by changing luminal ecology in vivo. These changes may affect the health and mucosal integrity of ileum used to construct these reservoirs.}, }
@article {pmid9666771, year = {1998}, author = {Denewer, A}, title = {A low-pressure rectosigmoid pouch created by side-to-side anastomosis with a stapling technique and sigmoid colon intussusception as an antireflux procedure.}, journal = {British journal of urology}, volume = {81}, number = {6}, pages = {856-861}, doi = {10.1046/j.1464-410x.1998.00649.x}, pmid = {9666771}, issn = {0007-1331}, mesh = {Adult ; Aged ; Anastomosis, Surgical/methods ; Colon, Sigmoid/transplantation ; Cystectomy/*methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Rectum/transplantation ; Stents ; Surgical Stapling/*methods ; Urinary Bladder Neoplasms/physiopathology/*surgery ; Urinary Diversion/*methods ; Urinary Incontinence/prevention &amp; control ; Urodynamics ; Vesico-Ureteral Reflux/prevention &amp; control ; }, abstract = {OBJECTIVE: To assess a new procedure of urinary diversion after cystectomy for bladder cancer.<br><br>PATIENTS AND METHODS: Thirty-two patients (14 women and 18 men, mean age 54 years, range 35-70) treated by radical cystectomy for bladder cancer underwent urinary diversion using a new technique. After mobilization of the sigmoid colon, the splenic flexure and the upper rectum, two adjacent colotomies were made to complete a stapled side-to-side anastomosis, with intussusception and implantation of the ureters between the layers of the intussusceptum. Two ureteric stents (8F) were brought out through the iliac fossa, and a rectal tube introduced through the anus and the intussusception to the proximal colon. The reservoir was assessed by urodynamic studies, using the anorectal perfusion catheter.<br><br>RESULTS: Twenty-eight patients were continent day and night, with mild soiling in the remaining four at night. Complications included a urinary fistula in three patients and a fecal fistula in one; all were treated conservatively. Metabolic complications occurred in only two patients.<br><br>CONCLUSION: The pouch created has a low pressure, a high capacity and provides effective continence. Surgery remains adequately radical, by removing the prostate and the membranous urethra. The implanted ureters between the layers of the intussusceptum provided an effective antireflux mechanism and markedly improved kidney function. The intussusception prevents reflux of the pouch contents into the proximal colon and minimizes metabolic complications. The technique needs neither colostomy nor small intestinal manipulations.}, }
@article {pmid9662959, year = {1998}, author = {Chieffi, PP and Sens, YA and Paschoalotti, MA and Miorin, LA and Silva, HG and Jabur, P}, title = {Infection by Cryptosporidium parvum in renal patients submitted to renal transplant or hemodialysis.}, journal = {Revista da Sociedade Brasileira de Medicina Tropical}, volume = {31}, number = {4}, pages = {333-337}, doi = {10.1590/s0037-86821998000400001}, pmid = {9662959}, issn = {0037-8682}, mesh = {Animals ; Cryptosporidiosis/epidemiology/*parasitology ; *Cryptosporidium parvum/isolation &amp; purification ; Feces/parasitology ; Female ; Humans ; Hypertension/parasitology ; Immunosuppression Therapy ; Incidence ; Kidney Failure, Chronic/*parasitology/therapy ; *Kidney Transplantation ; Male ; *Renal Dialysis ; }, abstract = {The frequency of infection by Cryptosporidium parvum was determined in two groups of renal patients submitted to immunosuppression. One group consisted of 23 renal transplanted individuals, and the other consisted of 32 patients with chronic renal insufficiency, periodically submitted to hemodialysis. A third group of 27 patients with systemic arterial hypertension, not immunosuppressed, was used as control. During a period of 18 months all the patients were submitted to faecal examination to detect C. parvum oocysts, for a total of 1 to 6 tests per patient. The results showed frequencies of C. parvum infection of 34.8%, 25% and 17.4%, respectively, for the renal transplanted group, the patients submitted to hemodialysis and the control group. Statistical analysis showed no significant differences among the three groups even though the frequency of C. parvum infection was higher in the transplanted group. However, when the number of fecal samples containing C. parvum oocysts was taken in account, a significantly higher frequency was found in the renal transplanted group.}, }
@article {pmid9654394, year = {1997}, author = {Keller, MS and Vane, DW}, title = {Graft length affects outcome in fetal small bowel transplants.}, journal = {Journal of investigative surgery : the official journal of the Academy of Surgical Research}, volume = {10}, number = {6}, pages = {375-378}, doi = {10.3109/08941939709099601}, pmid = {9654394}, issn = {0894-1939}, mesh = {Animals ; Female ; *Fetal Tissue Transplantation ; *Graft Survival ; Intestine, Small/*transplantation ; Omentum/*surgery ; Pregnancy ; *Pregnancy Outcome ; Rats ; Rats, Inbred F344 ; }, abstract = {Multiple studies have demonstrated the ability of the fetal rat small intestine to be transplanted successfully as a free graft, devoid of its mesentery. While maintaining normal histologic architecture, portal circulation, and digestive and absorptive properties, the initial myeloelectric activity is delayed. The purpose of this study was to investigate how abnormal early motility affects functional outcome and survival. Using a syngeneic model, fetal rat small intestine segments were transplanted into adolescent rat recipients as free grafts into the omentum. After a maturation period, viable segments measuring 1 or 2 cm were placed into continuity with the native intestine after a standardized resection of either jejunum-ileum, ileum-cecum, or cecum. Control animals had native intestinal resection without graft interposition. Survival, daily weight gain, oral intake, and fecal output were monitored. In this model, overall survival was improved with the use of the shorter 1-cm graft segment compared with the 2-cm and more distal interpositions. No animals survived with proximal graft placement after jejunal-ileal resection. Nutrient use was improved in the transplant recipients compared with nontransplant controls but did not differ between the two graft lengths. These data suggest that outcome in this model is improved using shorter fetal intestine graft lengths. The use of multiple segments in multistaged procedures and early defunctionalization may improve results.}, }
@article {pmid9645740, year = {1998}, author = {Adang, EM and Engel, GL and Rutten, FF and Geerdes, BP and Baeten, CG}, title = {Cost-effectiveness of dynamic graciloplasty in patients with fecal incontinence.}, journal = {Diseases of the colon and rectum}, volume = {41}, number = {6}, pages = {725-33; discussion 733-4}, doi = {10.1007/BF02236259}, pmid = {9645740}, issn = {0012-3706}, mesh = {Adult ; Aged ; Anal Canal/surgery ; Colostomy/economics ; Cost-Benefit Analysis ; Costs and Cost Analysis ; Digestive System Surgical Procedures/*economics ; Fecal Incontinence/economics/*surgery ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Prospective Studies ; Quality of Life ; Reoperation ; Sensitivity and Specificity ; }, abstract = {PURPOSE: This study evaluates the cost-effectiveness of dynamic graciloplasty for intractable fecal incontinence.<br><br>PATIENTS AND METHODS: The costs and effects of dynamic graciloplasty were measured in a prospective, longitudinal study and in a clinical trial. Forty-three patients with intractable fecal incontinence were evaluated before and after dynamic graciloplasty. Costs were obtained from the hospital information system and from patient-oriented questionnaires. We compared the costs of a dynamic graciloplasty with the costs of a colostomy. Colostomy costs were evaluated using a group of seven patients who had a stoma in place for incontinence for several years. Sensitivity analyses were included.<br><br>RESULTS: Total direct costs of lifelong dynamic graciloplasty were $31,733 (United States dollars), costs of lifelong conventional treatment were $12,180 (United States), and costs of colostomy, including lifelong stoma care, were $71,576 (United States). The clinical success rate of dynamic graciloplasty was 74 percent. Quality of life after successful dynamic graciloplasty was better than with conventional treatment.<br><br>CONCLUSION: We found that dynamic graciloplasty was more expensive than conventional treatment but resulted in a significantly higher quality of life. Stoma treatment was the least attractive alternative regarding both costs and effects. The Dutch Health Insurance Executive Board recommended reimbursement for the dynamic graciloplasty procedure.}, }
@article {pmid9638724, year = {1998}, author = {Gross, U and Frank, M and Doss, MO}, title = {Hepatic complications of erythropoietic protoporphyria.}, journal = {Photodermatology, photoimmunology &amp; photomedicine}, volume = {14}, number = {2}, pages = {52-57}, doi = {10.1111/j.1600-0781.1998.tb00011.x}, pmid = {9638724}, issn = {0905-4383}, mesh = {Adolescent ; Adult ; Cholestasis, Intrahepatic/etiology/therapy ; Coproporphyrins/metabolism ; Female ; Humans ; Liver Diseases/*etiology/surgery ; Liver Transplantation ; Male ; Middle Aged ; Porphyria, Hepatoerythropoietic/*complications/metabolism/therapy ; Protoporphyrins/metabolism ; Ursodeoxycholic Acid/therapeutic use ; }, abstract = {A quarter of patients with erythropoietic protoporphyria develop mild to severe cholestatic liver disease. The determination of early indicators of hepatobiliary involvement are of pivotal importance to select patients for choleretic therapy. Porphyrin parameters were studied during ursodeoxycholic acid treatment in eight patients with protoporphyrin-associated liver disease and eight patients with liver failure before and after liver transplantation. The patients with intrahepatic cholestasis exhibited excessive protoporphyrinemia (27 mumol/l) compared with controls (normal < 0.64 mumol/l). Fecal protoporphyrin excretion decreased in patients with deterioration of liver function, whereas urinary coproporphyrin increased up to 2290 nmol/24 h (normal < 119 nmol/24 h). Coproporphyrin isomer I proportion increased to 71 +/- 10% (mean +/- SD, n = 8) in patients with terminal liver failure (normal < 31%). During therapy with ursodeoxycholic acid biochemical improvement occurred but without clinical remission in most cases. Eight patients underwent liver transplantation between 1987 and 1997. One patient died of liver failure. Two transplant recipients are in a good condition since 8 and 9 years, respectively. All explanted livers revealed micronodular cirrhosis and high protoporphyrin levels of about 25,000-fold (mean, n = 3). Immediately after liver transplantation protoporphyrin in erythrocytes decreased to 46-96% of pre-operative values. Coproporphyrin remained moderately elevated due to post-operative cholestasis. A post-operative rise in fecal protoporphyrin elimination reflected sufficient biliary clearence of protoporphyrin by the transplant. In conclusion, moderate coproporphyrinuria with isomer I is the earliest sign of liver complications in erythropoietic protoporphyria. Progression of protoporphyrin induced toxic liver injury is indicated by excessive protoporphyrinemia and coproporphyrinuria with an isomer I proportion > 71 +/- 10%, and reduction of fecal protoporphyrin excretion. Results suggest that therapy of intrahepatic cholestasis with ursodeoxycholic acid is only effective in the initial stages of liver disease in erythropoietic protoporphyria. In patients with severe cholestatic hepatic failure, liver transplantation is the treatment of choice.}, }
@article {pmid9619864, year = {1998}, author = {Sadzuka, Y and Hirotsu, S and Hirota, S}, title = {Effect of liposomalization on the antitumor activity, side-effects and tissue distribution of CPT-11.}, journal = {Cancer letters}, volume = {127}, number = {1-2}, pages = {99-106}, doi = {10.1016/s0304-3835(98)00031-7}, pmid = {9619864}, issn = {0304-3835}, mesh = {Animals ; Antineoplastic Agents, Phytogenic/*administration &amp; dosage/metabolism/pharmacology ; Bile/chemistry ; Body Weight/drug effects ; Camptothecin/administration &amp; dosage/adverse effects/*analogs &amp; derivatives/analysis/metabolism/pharmacology ; Carcinoma, Ehrlich Tumor/metabolism ; *Drug Carriers ; Feces/chemistry ; Irinotecan ; *Liposomes ; Liver/chemistry ; Male ; Mice ; Neoplasm Transplantation ; Water/analysis ; }, abstract = {We have examined the efficacy of liposomalization and polyethyleneglycol (PEG) modification of liposomes on the antitumor activity, side-effects and tissue distribution of irinotecan hydrochloride (CPT-11). PEG-liposome was confirmed to elevate the plasma circulation of CPT-11 and SN-38 (active metabolite) concentrations. The tumor accumulation of CPT-11 and SN-38 was increased by the PEG-modified liposomes. The antitumor activity of CPT-11 increased due to the elevated tumor distribution of CPT-11 and SN-38 levels by the PEG-modified liposomes. In the tumor, CPT-11 was converted to SN-38. Thus, it is considered that passive targeting to the tumor by liposomalization elevated the SN-38 level in the tumor especially and increased the antitumor activity of CPT-11. Furthermore, intestinal disorder, a side toxicity of CPT-11, decreased dependent on the CPT-11 and SN-38 concentrations in the bile by liposomalization. Although the liposomes induce improved tissue distribution of the prodrug, the tissue distribution of active metabolites does not always improve. However, CPT-11-entrapped liposome was useful, as CPT-11 is converted to SN-38 in the tumor. These results suggested that the usefulness of CPT-11 could be extended.}, }
@article {pmid9568856, year = {1998}, author = {Arvanitidou, M and Spaia, S and Katsinas, C and Pangidis, P and Constantinidis, T and Katsouyannopoulos, V and Vayonas, G}, title = {Microbiological quality of water and dialysate in all haemodialysis centres of Greece.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {13}, number = {4}, pages = {949-954}, doi = {10.1093/ndt/13.4.949}, pmid = {9568856}, issn = {0931-0509}, mesh = {Bacteria/*isolation &amp; purification ; Humans ; *Renal Dialysis ; *Water Microbiology ; }, abstract = {BACKGROUND: Bacterial contamination of treated water and dialysate comprises an important problem for patients undergoing haemodialysis. Both the progressive reduction of the thickness of cellulose membranes and the expanding use of high-flux membranes probably enhance the risk of pyrogenic reactions, therefore increasing the need for atoxic water and non-pyrogenic dialysis fluid.<br><br>METHODS: Samples of tap water, treated water, and effluent dialysate in all 85 haemodialysis centres in Greece were examined for total heterotrophic bacteria counts employing the pour plate method, total and faecal coliforms, faecal streptococci and pseudomonas spp. using the membrane filter technique, and sulphite-reducing clostridia applying the most probable number method. Overall 255 paired samples were tested from January to March 1997.<br><br>RESULTS: For total heterotrophic bacteria, the overall compliance of treated water and dialysate to the American Association of Medical Instrumentation standards (<200 c.f.u./ml for water and <2000 c.f.u./ml for dialysate) was 92.6 and 63.7% respectively, whereas the compliance of tap water samples to our national standards (total heterotrophic bacteria < 10 c.f.u./ml and absence of the other indicator bacteria) was 80.7%. The most commonly isolated bacteria were pseudomonas spp., found in 22.2% of treated water and 59.5% of dialysate samples, whereas the respective frequencies were 12.3 and 36.2% for total coliforms, 8.6 and 30.0% for faecal coliforms, 14.8 and 28.7% for faecal streptococci, and sulphite-reducing clostridia were isolated in 5.8% of dialysate samples only. Haemodialysis centres equipped with storage tanks for treated water experienced lower levels of total heterotrophic bacteria, but higher counts of total and faecal coliforms, faecal streptococci, and pseudomonas spp., although the difference was statistically significant only for faecal streptococci counts, (P<0.05). Sixty-seven haemodialysis centres were equipped with bacterial filters, but mean values of all the examined microorganisms were not statistically different from those of the other centres. Faecal streptococci counts in treated water samples were positively correlated with ageing of both haemodialysis centres (P<0.005) and purification system (P<0.05), whereas pseudomonas counts were significantly correlated with ageing of the purification system (P<0.05).}, }
@article {pmid9560801, year = {1998}, author = {Pakarinen, MP and Halttunen, J and Kuusanmäki, P and Lauronen, J and Miettinen, TA}, title = {Absorption, excretion, and distribution of plant sterols after proximal gut resection and autotransplantation of porcine ileum.}, journal = {Lipids}, volume = {33}, number = {3}, pages = {267-276}, pmid = {9560801}, issn = {0024-4201}, mesh = {Animals ; Bile/metabolism ; Cholesterol/analogs &amp; derivatives/metabolism ; Denervation/adverse effects ; Feces/chemistry ; Ileum/*metabolism/surgery ; Intestinal Absorption/*physiology ; Phytosterols/*metabolism ; Sitosterols/metabolism ; Swine ; Transplantation, Autologous/physiology ; }, abstract = {Contribution of different gut segments to plant sterol absorption, adaptation of plant sterol absorption after partial small bowel resection, and effects of gut transplantation (necessitates extrinsic autonomic denervation and lymphatic disruption) on plant sterol biodynamics are unclear. We studied the consequences of massive proximal small bowel resection and autotransplantation of the remaining ileum on the adaptive absorption and biodynamics of plant sterols. Dietary, fecal, biliary, hepatic and plasma plant sterols, fecal elimination and absorption of cholesterol, small bowel morphology, and intestinal transit were determined before (n = 5) and at 4, 8, and 14 wk after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum (n = 15) or transection (n = 5). Proximal gut resection significantly reduced cholesterol absorption efficiency; percentage absorption and biliary secretion of plant sterols; plasma, biliary and hepatic campesterol-to-cholesterol proportions; and sitosterol proportions in plasma and bile. Autotransplantation of the remaining ileum further significantly decreased cholesterol absorption efficiency; percentage absorption and biliary secretion of campesterol; campesterol proportions in plasma, bile and liver; and plasma proportions of sitosterol while increasing fecal excretion of neutral and acidic steroids. Plasma proportions of the two plant sterols, but absorption of just campesterol, were gradually improved with increasing cholesterol absorption and villus height after proximal gut resection; the same result was observed to a lesser degree after ileal autotransplantation. In addition, significant positive correlations were found between percentage cholesterol and campesterol absorption and the plasma plant sterol proportions in both proximal resection groups, between campesterol absorption and ileal villus height in the resection group, and between campesterol absorption and intestinal transit time in the autotransplantation group. In conclusion, plasma campesterol and sitosterol closely reflect absorption of cholesterol and plant sterols from intact and autotransplanted ileum during adaptation to proximal gut resection. A loss of proximal gut absorptive surface impairs cholesterol and campesterol absorption more than sitosterol absorption, the latter being apparently less dependent on available jejunal villus surface area.}, }
@article {pmid9560117, year = {1998}, author = {Rosen, HR and Novi, G and Zoech, G and Feil, W and Urbarz, C and Schiessel, R}, title = {Restoration of anal sphincter function by single-stage dynamic graciloplasty with a modified (split sling) technique.}, journal = {American journal of surgery}, volume = {175}, number = {3}, pages = {187-193}, doi = {10.1016/s0002-9610(97)00289-4}, pmid = {9560117}, issn = {0002-9610}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/*physiopathology/*surgery ; *Electric Stimulation Therapy ; Fecal Incontinence/etiology/physiopathology/*therapy ; Female ; Humans ; Male ; Manometry ; Middle Aged ; Muscle, Skeletal/*transplantation ; Postoperative Complications ; Rectal Neoplasms/complications/physiopathology/*surgery ; Surgical Procedures, Operative/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Controlled muscle fiber conversion by electrostimulation makes transformation of fast twitching type II muscle fibers to slow twitching type I fibers possible, which gives skeletal muscles the capacity for tetanic contraction. This phenomenon has been recently applied in the so-called "dynamic graciloplasty" to restore function of an insufficient or excised anal sphincter. This paper describes our results with this method in patients with fecal incontinence or following an abdomino-perineal resection (APR) of the anorectum.<br><br>METHODS: From April 1992 through April 1997, 28 patients (12 women and 16 men) were treated by dynamic graciloplasty. The median age was 53.5 years (range 16 to 79). Indications were as follows: APR + synchronous restoration of the excised sphincter by graciloplasty (n = 12); total anorectal reconstruction (TAR) following APR in the past (n = 6); Patients with acquired fecal incontinence (n = 4); and Congenital atresia (n = 6). Muscle transposition, implantation of stimulation electrodes and pulse generator were done as a single-stage procedure, the "neosphincter" was wrapped in a modified technique (split-sling technique). Muscle transformation was performed by controlled neuromuscular stimulation during 8 weeks (from 1992 to 1995) and 4 weeks (since 1996), respectively.<br><br>RESULTS: No postoperative mortality (90 days) was observed in either group. In our early experience, rectal injury occurred in 4 patients as the most prominent complication. Evaluation of the functional outcome showed the best results in patients operated either for congenital of acquired incontinence who achieved a continence for solids and liquids or solids alone, respectively (1 or 2 according to Williams' score) in 90%, while patients following APR showed a satisfying outcome (continence for solids and liquids, solids alone or with occasional episodes for liquids) in only 55.5%. In patients following APR, defecation disorders turned out to be the most prominent functional problem and had to be treated by enemas.<br><br>CONCLUSION: In this series, we have been able to perform dynamic graciloplasty as a one-stage procedure using a modified muscle wrap (split-sling-technique) thus reducing the time period until continence could be achieved to 7 weeks. We found the appropriate tension of the muscle wrap essential to prevent direct injury to the rectum as it was seen in our early experience. For this reason, we have introduced a modified device to perform intraoperative anal manometry and to measure pressures created by the neosphincter objectively.}, }
@article {pmid9548628, year = {1998}, author = {Pakarinen, MP and Halttunen, J and Kuusanmäki, P and Miettinen, TA}, title = {Increased plasma, biliary, and hepatic cholesterol precursors in pigs with ileal autotransplantation-induced malabsorption of cholesterol and bile acids.}, journal = {Scandinavian journal of gastroenterology}, volume = {33}, number = {3}, pages = {319-326}, doi = {10.1080/00365529850170937}, pmid = {9548628}, issn = {0036-5521}, mesh = {Animals ; Bile Acids and Salts/*metabolism ; Biliary Tract/metabolism ; Cholesterol/blood/*metabolism ; Chromatography, Gas ; Feces/chemistry ; Female ; Ileum/transplantation ; Intestinal Absorption ; Liver/metabolism ; Malabsorption Syndromes/*metabolism ; Swine ; }, abstract = {BACKGROUND: Small-bowel transplantation impairs intestinal absorptive function for unknown reasons.<br><br>METHODS: The proportions of plasma, biliary, and hepatic cholesterol precursors to cholesterol were determined by gas-liquid chromatography after resection of the proximal 75% of the porcine jejunoileum (n = 15) and autotransplantation of the remaining ileum (n = 15) and were related to in vivo absorption and fecal excretion of cholesterol.<br><br>RESULTS: Ileal autotransplantation significantly decreased serum (18%; P < 0.05) and liver (7.6%; P < 0.05) cholesterol content, the esterification percentage of serum cholesterol (5.1%; P < 0.0001), and the total amount of cholesterol absorbed (48%; P < 0.05) and increased fecal excretion of bile acids (108%; P < 0.0001), net cholesterol elimination (53%; P < 0.001), and the proportions of plasma (207%; P < 0.0001), biliary (183%; P < 0.0001), and hepatic (114%; P < 0.0001) cholesterol precursors. The increases were most striking for the side-chain-saturated demethylated sterols, cholesterol and lathosterol, and monomethyl sterols, whose bile/liver and plasma/liver ratios were increased in the autotransplantation group. Plasma, biliary, and hepatic precursor proportions were positively related to each other and similarly correlated with fecal bile acids and the net elimination of cholesterol in feces.<br><br>CONCLUSIONS: These findings suggest that ileal autotransplantation in pigs with proximal gut resection increased the levels of cholesterol precursor sterols in plasma, bile, and liver mainly due to a bile-acid-malabsorption-induced increase in hepatic synthesis of cholesterol. Enhanced secretion of cholesterol precursors from the liver into the plasma and bile may have contributed to their increased values during the increased rate of cholesterogenesis.}, }
@article {pmid9514319, year = {1998}, author = {Girsch, W and Rab, M and Mader, N and Kamolz, LP and Hausner, T and Schima, W and Gruber, H}, title = {Considerations on stimulated anal neosphincter formation: an anatomic investigation in search of alternatives to the gracilis muscle.}, journal = {Plastic and reconstructive surgery}, volume = {101}, number = {4}, pages = {889-95; discussion 896-8}, doi = {10.1097/00006534-199804040-00001}, pmid = {9514319}, issn = {0032-1052}, mesh = {Anal Canal/innervation/*surgery ; Electric Stimulation ; Fecal Incontinence/surgery ; Female ; Humans ; Male ; Muscle, Skeletal/blood supply/innervation/*transplantation ; Thigh ; }, abstract = {Electrically stimulated anal neosphincter formation with transposed gracilis is performed clinically in an increasing number of patients. The use of a stimulated gluteus maximus in this application has been reported also. The question arises whether or not an optimal design for such a procedure has already been ascertained. An anatomic study was performed on 30 human cadavers to evaluate the semitendinosus muscle and its suitability for construction of a stimulated anal neosphincter. Semitendinosus fulfilled requirements for transposition around the anal canal in all cases. The muscle length was found adequate for transposition; nerve and vascular supply provided a suitable arc of rotation. The pattern of innervation might allow selective stimulation of that particular part of the muscle, which is intended to restore sphincter function. For clinical application, a vascular delay procedure is strongly recommended.}, }
@article {pmid9501717, year = {1998}, author = {Kamm, MA}, title = {Faecal incontinence.}, journal = {BMJ (Clinical research ed.)}, volume = {316}, number = {7130}, pages = {528-532}, doi = {10.1136/bmj.316.7130.528}, pmid = {9501717}, issn = {0959-8138}, mesh = {Behavior Therapy ; Biofeedback, Psychology ; *Fecal Incontinence/etiology/surgery/therapy ; Humans ; Muscle, Skeletal/transplantation ; Transcutaneous Electric Nerve Stimulation ; }, }
@article {pmid9491418, year = {1998}, author = {Christensen, CM and Nansen, P and Bjørn, H and Hansen, NP}, title = {Experimental hybridization between Oesophagostomum dentatum and O. quadrispinulatum in pigs.}, journal = {Parasitology research}, volume = {84}, number = {1}, pages = {1-6}, doi = {10.1007/s004360050347}, pmid = {9491418}, issn = {0932-0113}, mesh = {Animals ; Crosses, Genetic ; Feces/parasitology ; Female ; *Hybridization, Genetic ; Male ; Oesophagostomiasis/parasitology/*veterinary ; Oesophagostomum/anatomy &amp; histology/*genetics/growth &amp; development/physiology ; Swine/parasitology ; Swine Diseases/*parasitology ; }, abstract = {To investigate eventual hybridization between two nodular worm species of pigs, Oesophagostomum dentatum and O. quadrispinulatum, we used either mature, adult worms or 10-day-old fourth-stage larvae (L4) as starting material, employing a nonsurgical transplantation technique. Following the transfer of adult worms the ensuing first generation of larvae gave rise to adult worms that were found by morphological examination to be purely O. dentatum. Therefore, we decided to use the immature L4 as starting material. After the transfer of L4 to recipient pigs, fecal cultures were established and the L3 derived from the O. dentatum male O. quadrispinulatum female cross gave rise to adult but infertile worms, which morphologically had the sexual characters of their parent generation, whereas other characteristics were intermediate between the two species. Attempts to reproduce the hybrid worms or the reciprocal cross were unsuccessful, indicating that hybridization between the two species is a rarely occurring phenomenon.}, }
@article {pmid9470421, year = {1997}, author = {Ansorg, R and van den Boom, R and Rath, PM}, title = {Detection of Aspergillus galactomannan antigen in foods and antibiotics.}, journal = {Mycoses}, volume = {40}, number = {9-10}, pages = {353-357}, doi = {10.1111/j.1439-0507.1997.tb00249.x}, pmid = {9470421}, issn = {0933-7407}, mesh = {Air Microbiology ; Anti-Bacterial Agents/*analysis/immunology ; Antigens, Fungal/*analysis ; Aspergillosis/diagnosis ; Aspergillus/*immunology ; *Drug Contamination ; False Positive Reactions ; Feces/microbiology ; *Food Microbiology ; Galactose/analogs &amp; derivatives ; Humans ; Latex Fixation Tests ; Mannans/*analysis/immunology ; }, abstract = {The specificity of the Pastorex Aspergillus latex agglutination test for the diagnosis of manifest aspergillosis is hampered by the occurrence of false-positive results. In order to prove whether or not the false-positive reactions may be caused by the uptake of the soluble galactomannan antigen from the environment, the presence of the antigen was tested in foods, air samples, antibiotics for therapeutic use and faeces. Reactions of the Aspergillus latex agglutination test were found in 15 (79%) out of 19 samples of meals prepared in a hospital kitchen, in five out of six canned vegetables from a supermarket, in all of six samples of pasta and rice bought in health shops, in the faeces of four bone marrow transplant (BMT) recipients and of four healthy subjects and in one and two batches of the antibiotics co-amoxyclav and piperacillin respectively. The concentration of the antigen in faecal material was calculated to be in the range of 1.2-38.4 micrograms g-1. It is concluded that the faecal galactomannan antigen may reach the circulation in patients with dysfunction of the intestinal mucosal barrier, e.g. BMT recipients, thus leading to diagnostically false-positive antigenaemia.}, }
@article {pmid9466537, year = {1998}, author = {McGrath, D and Falagas, ME and Freeman, R and Rohrer, R and Fairchild, R and Colbach, C and Snydman, DR}, title = {Adenovirus infection in adult orthotopic liver transplant recipients: incidence and clinical significance.}, journal = {The Journal of infectious diseases}, volume = {177}, number = {2}, pages = {459-462}, doi = {10.1086/517375}, pmid = {9466537}, issn = {0022-1899}, support = {AI-07329/AI/NIAID NIH HHS/United States ; }, mesh = {Adenoviridae/growth &amp; development/isolation &amp; purification ; Adenovirus Infections, Human/blood/*epidemiology/urine ; Adolescent ; Adult ; Biopsy ; Cells, Cultured ; Colon/virology ; Feces/virology ; Humans ; Incidence ; Liver/virology ; Liver Transplantation/*adverse effects ; Lung/virology ; Middle Aged ; Pneumonia, Viral/diagnosis/mortality ; Retrospective Studies ; }, abstract = {Adenovirus infection occurs in 10% of pediatric orthotopic liver transplant recipients; however, no cases have been described in adult liver transplant recipients. A retrospective review of 191 adults who underwent liver transplantation from January 1988 through October 1995 was done to describe the incidence and clinical significance of adenovirus infection in this population. There were 11 (5.8%) patients with 16 cultures positive for adenovirus. Sites of isolation were urine (9), blood (2), liver biopsy (2), colonic biopsy (1), lung biopsy (1), and stool (1). Adenovirus infection was classified as either disease or asymptomatic infection. There were 7 cases of adenovirus disease (2 definite, 1 probable, and 4 possible). Disease was disseminated in 3 patients: All had pneumonia and 2 died. Of the 3 patients with pneumonia, 2 had evidence of multiorgan involvement. Adenovirus disease occurs in adult orthotopic liver transplant recipients and may be associated with significant morbidity and occasional mortality.}, }
@article {pmid9462392, year = {1998}, author = {Christiansen, J and Rasmussen, OO and Lindorff-Larsen, K}, title = {Dynamic graciloplasty for severe anal incontinence.}, journal = {The British journal of surgery}, volume = {85}, number = {1}, pages = {88-91}, doi = {10.1046/j.1365-2168.1998.00506.x}, pmid = {9462392}, issn = {0007-1323}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/*surgery ; Electric Stimulation ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Patient Satisfaction ; Surgical Flaps ; Treatment Outcome ; }, abstract = {BACKGROUND: The surgical options for the treatment of anal incontinence where standard procedures have failed include transposition of striated muscles, primarily gracilis and gluteus maximus, and implantation of artificial sphincters. Due to a high proportion of fatigue-prone fibres in striated muscles, the results of transposition without stimulation have been disappointing. This study presents the results of stimulated graciloplasty in 13 patients with severe anal incontinence in whom other surgical procedures had failed.<br><br>METHODS: The gracilis muscle was transposed around the anal canal according to a previously described technique. Eight weeks later the intramuscular electrodes were implanted into the gracilis at the site of the nerve entry and a neurostimulator was placed in a subcutaneous pocket in the abdominal wall. The patients were followed from 7 to 27 months.<br><br>RESULTS: Six patients obtained satisfactory continence and five showed marked improvement. Two patients were considered failures. Rectal evacuation problems occurred in three patients, in one so severe that the patient, in spite of satisfactory continence, considered the treatment a failure.<br><br>CONCLUSION: Dynamic graciloplasty is a viable option in carefully selected patients with severe anal incontinence where other methods have failed.}, }
@article {pmid9430887, year = {1997}, author = {Peraldi, MN and Akposso, K and Haymann, JP and Lahlou, A and Sraer, JD}, title = {Haemolytic-uraemic syndrome in patients with Crohn's disease.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {12}, number = {12}, pages = {2744-2745}, doi = {10.1093/ndt/12.12.2744}, pmid = {9430887}, issn = {0931-0509}, mesh = {Adult ; Bacterial Toxins/analysis ; Crohn Disease/*complications ; Feces/chemistry ; Hemolytic-Uremic Syndrome/*etiology/physiopathology ; Humans ; Male ; Shiga Toxin 2 ; }, }
@article {pmid9407995, year = {1997}, author = {Shatari, T and Kawahara, H and Kodaira, S}, title = {New pathway for leads in dynamic graciloplasty.}, journal = {Diseases of the colon and rectum}, volume = {40}, number = {12}, pages = {1511-1512}, doi = {10.1007/BF02070722}, pmid = {9407995}, issn = {0012-3706}, mesh = {Anal Canal/physiopathology ; Electric Stimulation/*methods ; Electrodes ; Fecal Incontinence/physiopathology/*surgery ; Humans ; Muscle, Skeletal/physiopathology/*transplantation ; Safety ; Surgical Flaps ; Thigh/surgery ; }, abstract = {Dynamic graciloplasty is one of the methods now used to re-establish anal function. Among complications, pain in the local tissue and skin irritation have been reported, both caused by lead wires. By passing the leads posterior to the adductor longus muscle, the wires do not irritate the local skin and are fixed well without sutures. We performed this procedure in three patients, with good results. The technique is easy, and complications involving the lead wires were minimized.}, }
@article {pmid9373296, year = {1997}, author = {Cavina, E and Seccia, M and Chiarugi, M and Banti, P and Zocco, G}, title = {Laparoscopically assisted abdominoperineal resection and simultaneous total anorectal reconstruction with electrostimulated static-dynamic graciloplasty.}, journal = {Surgical endoscopy}, volume = {11}, number = {12}, pages = {1209-1212}, doi = {10.1007/s004649900571}, pmid = {9373296}, issn = {0930-2794}, mesh = {Abdomen/*surgery ; Adult ; Anal Canal/*surgery ; Anus Neoplasms/surgery ; Blood Transfusion ; Body Image ; Colostomy ; Electric Stimulation ; Electrodes, Implanted ; Fecal Incontinence/surgery ; Female ; Humans ; *Laparoscopy ; Minimally Invasive Surgical Procedures ; Muscle, Skeletal/*transplantation ; Peritoneum/*surgery ; Postoperative Hemorrhage/etiology ; Quality of Life ; *Plastic Surgery Procedures ; Rectal Neoplasms/surgery ; Rectum/*surgery ; Reproducibility of Results ; Surgically-Created Structures ; Treatment Outcome ; }, abstract = {Bilateral electrostimulated graciloplasty, performed in a "static-dynamic" configuration around a perineal colostomy (total anorectal reconstruction-TAR), has been proven a reliable way to restore continence in patients who undergo to abdomino perineal resection (A.Pe.R.) of the anorectum for lower rectal cancer. In selected cases, laparoscopically assisted TAR can significantly improve body-image preservation and aesthetic results. A 33-year-old woman affected by lower rectal cancer was submitted to laparoscopic-assisted A.Pe.R and TAR with simultaneous bilateral graciloplasty; a suprapubic median mini-access was adopted to fully mobilize the mesorectum in absence of pneumoperitoneum. A subcutaneous pulse generator and special electrodes were also implanted to chronically electrostimulate the graciloplasty. In spite of postoperative bleeding which required a blood transfusion, postoperative outcome was satisfactory; electrostimulation was started on the 10th postoperative (p.o.) day and the patient was discharged on the 17th p.o. day. Two months after TAR, level II continence (N.S. Williams Scale) was achieved. In selected cases, laparoscopically assisted A.Pe.R. and TAR can be safely adopted to preserve body image and quality of life, avoiding at the same time a large abdominal approach and a "permanent" abdominal colostomy.}, }
@article {pmid9369896, year = {1997}, author = {Pakarinen, MP and Miettinen, TA and Kuusanmäki, P and Lauronen, J and Vento, P and Raivio, P and Halttunen, J}, title = {Adaptive lipid metabolism after ileal autotransplantation in pigs with proximal gut resection.}, journal = {Surgery}, volume = {122}, number = {5}, pages = {950-961}, doi = {10.1016/s0039-6060(97)90337-8}, pmid = {9369896}, issn = {0039-6060}, mesh = {Animals ; Body Weight ; Cholesterol/blood ; *Cholesterol, Dietary ; *Dietary Fats ; Female ; Gastrointestinal Transit ; Ileum/*physiology/surgery/*transplantation ; *Intestinal Absorption ; *Lipid Metabolism ; Lipoproteins/blood ; Phospholipids/blood ; Regression Analysis ; Sterols/blood ; Swine ; Time Factors ; Transplantation, Autologous/*physiology ; Triglycerides/blood ; Vitamin E/blood ; }, abstract = {BACKGROUND: Transplantation of the small intestine impairs intestinal absorptive function, but the adaptive response of a segmental graft is unknown. The aim of this study was to investigate the effects of ileal autotransplantation on the adaptive absorption and metabolism of lipids in pigs that had undergone proximal gut resection.<br><br>METHODS: Serum lipids, plasma vitamins A and E, absorption and excretion of cholesterol, bile acids and fat, plasma cholesterol precursor and plant sterol proportions to cholesterol (respective markers of cholesterol synthesis and absorption), enteric structure, and transit were determined 4, 8, and 14 weeks after 75% proximal resection with (n = 15) or without (n = 15) autotransplantation of the remaining ileum.<br><br>RESULTS: As compared with pigs that underwent proximal gut resection, the additional autotransplantation reduced the adaptive increase in total serum and high-density lipoprotein cholesterol, plasma plant sterol proportions and vitamin E concentrations, cholesterol and fat absorption efficiency, and villus height (p < 0.05 for all) during the 14 postoperative weeks and resulted in increases of up to 4.6, 2.7, 1.3, and 2.1 times the plasma cholesterol precursors (p < 0.005), fecal excretion of bile acids (p < 0.0005), neutral steroids (p < 0.005), and net elimination of cholesterol (p < 0.0005), respectively. Cholesterol and fat absorption and plasma plant sterols were significantly enhanced between 8 and 14 weeks after autotransplantation (p < 0.05, p < 0.005, and p < 0.05, respectively), whereas fecal elimination of cholesterol remained increased until the end of the follow-up.<br><br>CONCLUSIONS: Autotransplantation of the ileum in pigs that have undergone proximal small bowel resection disturbs the adaptive absorption of cholesterol, bile acids, fat, and fat-soluble vitamins, resulting, through increased fecal elimination of cholesterol, in decreased serum cholesterol despite a marked compensatory increase in cholesterol synthesis.}, }
@article {pmid9365684, year = {1997}, author = {Hjortrup, A and Rasmussen, A and Hansen, BA and Høiby, N and Heslet, L and Moesgaard, F and Kirkegaard, P}, title = {Early bacterial and fungal infections in liver transplantation after oral selective bowel decontamination.}, journal = {Transplantation proceedings}, volume = {29}, number = {7}, pages = {3106-3110}, doi = {10.1016/s0041-1345(97)81730-7}, pmid = {9365684}, issn = {0041-1345}, mesh = {Adolescent ; Adult ; Ampicillin/therapeutic use ; Analysis of Variance ; Anti-Bacterial Agents/*therapeutic use ; *Antibiotic Prophylaxis ; Antifungal Agents/*therapeutic use ; Bacterial Infections/classification/*epidemiology/prevention &amp; control ; Ceftriaxone/therapeutic use ; Cefuroxime/therapeutic use ; Child ; Child, Preschool ; Feces/microbiology ; Graft Rejection/epidemiology ; Humans ; Infant ; *Liver Transplantation ; Middle Aged ; Mycoses/*epidemiology/prevention &amp; control ; Nystatin/*therapeutic use ; Postoperative Complications/*epidemiology ; Regression Analysis ; Retrospective Studies ; Risk Factors ; Tobramycin/therapeutic use ; }, }
@article {pmid9379279, year = {1997}, author = {Schad, GA and Thompson, F and Talham, G and Holt, D and Nolan, TJ and Ashton, FT and Lange, AM and Bhopale, VM}, title = {Barren female Strongyloides stercoralis from occult chronic infections are rejuvenated by transfer to parasite-naive recipient hosts and give rise to an autoinfective burst.}, journal = {The Journal of parasitology}, volume = {83}, number = {5}, pages = {785-791}, pmid = {9379279}, issn = {0022-3395}, support = {R01 AI22662/AI/NIAID NIH HHS/United States ; RR 02483/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Chronic Disease ; Dogs ; Feces/parasitology ; Female ; Fertility ; Intestinal Diseases, Parasitic/immunology/*parasitology ; Intestines/parasitology/pathology/ultrastructure ; Larva/physiology ; Male ; Ovary/pathology/ultrastructure ; Strongyloides stercoralis/immunology/*physiology/ultrastructure ; Strongyloidiasis/immunology/*parasitology ; }, abstract = {It is widely assumed that barren Strongyloides stercoralis occurring in chronically infected carriers can become fecund when immunity wanes. Evidence for this involves corticosteroid treatment of hosts harboring occult infections that subsequently return to patency. However, nematodes have ecdysteroid receptors, and it has been suggested that corticosteroids act directly on the parasite, inducing autoinfective development, rather than indirectly by suppressing host immunity. To test these competing concepts, barren females were recovered from donor dogs when the dogs' fecal examinations turned negative. Groups of 100 active barren worms were surgically transplanted into the small intestines of each of 6 naive canine recipients. Three were examined at necropsy at 4-5 days postinfection (PI), before autoinfection could amplify the number of successfully transferred parasites. The remaining recipients were examined 21-22 days PI when, if autoinfection had occurred, the worm populations should have increased. At 4-5 days, gravid worms occurred in each of the recipients (19 +/- 6 worms/dog). By 21-22 days, a remarkable population increase had occurred (522.6 +/- 296 worms/dog). Worms from chronically infected donors were stunted, and electron microscopy revealed damage to the intestine and ovaries. Successfully transplanted worms recovered at days 4-5 PI were ovigerous and less stunted and showed repair of intestinal and ovarian tissues.}, }
@article {pmid9291891, year = {1997}, author = {Czirók, E and Prinz, GY and Dénes, R and Reményi, P and Herendi, A}, title = {Value of surveillance cultures in a bone marrow transplantation unit.}, journal = {Journal of medical microbiology}, volume = {46}, number = {9}, pages = {785-791}, doi = {10.1099/00222615-46-9-785}, pmid = {9291891}, issn = {0022-2615}, mesh = {Antibiotic Prophylaxis ; Bacteria/*isolation &amp; purification ; Bacterial Infections/*diagnosis ; Blood/microbiology ; *Bone Marrow Transplantation ; Candida/isolation &amp; purification ; Digestive System/microbiology ; Feces/microbiology ; Female ; Hospital Units ; Humans ; Infection Control ; Male ; Nose/microbiology ; Penis/microbiology ; Pharynx/microbiology ; Predictive Value of Tests ; Skin/microbiology ; Sputum/microbiology ; Urine/microbiology ; Vagina/microbiology ; }, abstract = {Because of the increased risk of infection with the associated diagnostic and therapeutic problems in bone marrow transplantation (BMT) patients, the usefulness of surveillance cultures (SC) at the BMT department of the National Institute of Haematology, Blood Transfusion, Transplantation and Immunology, Budapest, was reviewed. Between January 1992 and May 1995, 26 BMT operations were performed; 13 patients had 23 febrile espisodes. In 12 of these episodes infection was clinically documented; however, SC of these patients yielded bacteria identical with those in the blood culture in only two episodes (1 and 6 days before their blood cultures became positive, respectively). Out of a total of 1187 samples from these patients, potentially pathogenic bacteria were isolated from 145 SC and 43 blood cultures (drawn on 31 different days). Suppression of the gastrointestinal flora could be achieved by the department's decontamination regimen; however, overgrowth by gram-positive organisms (mainly coagulase-negative staphylococci) occurred in the intestine and at other body sites. On the basis of these results, SC are of limited value in predicting infection or identifying the causative organisms of fever. On the other hand, SC are useful in confirming the efficiency of suppression of the body flora by antimicrobial agents. Specific treatment was based on suitably sampled materials, and close contact between physicians, infectious disease specialists and microbiologists was essential.}, }
@article {pmid9278660, year = {1997}, author = {Geerdes, BP and Kurvers, HA and Konsten, J and Heineman, E and Baeten, CG}, title = {Assessment of ischaemia of the distal part of the gracilis muscle during transposition for anal dynamic graciloplasty.}, journal = {The British journal of surgery}, volume = {84}, number = {8}, pages = {1127-1129}, pmid = {9278660}, issn = {0007-1323}, mesh = {Adolescent ; Adult ; Anal Canal/surgery ; Blood Flow Velocity ; Cadaver ; Colostomy/*methods ; Constriction ; Fecal Incontinence/*surgery ; Humans ; Ischemia/*physiopathology ; Laser-Doppler Flowmetry ; Middle Aged ; Muscle, Skeletal/*blood supply/*transplantation ; Surgical Flaps ; }, abstract = {BACKGROUND: Dynamic graciloplasty is used to create a neosphincter in patients with intractable faecal incontinence. When mobilizing the distal gracilis muscle from the upper leg, the minor vascular pedicles have to be ligated. This can interfere with the vascular supply in this part of the muscle.<br><br>METHODS: The arterial anatomy within the muscle was visualized by means of angiography of 11 postmortem specimens. To quantify potential acute ischaemia, blood flow in the distal gracilis muscle was measured in ten patients with laser Doppler flowmetry during mobilization of the muscle.<br><br>RESULTS: Angiography showed that the main vascular pedicle and all minor pedicles drain into one and the same arterial system. After clamping of the minor vascular pedicles, blood flow (mean 25.8 (range 6.5-74.3) perfusion units) did not differ from values obtained before clamping (mean 25.4 (range 7.5-68.7) perfusion units). After a mean of 1.8 years, all muscles were vital. No correlation existed between the change in muscle blood flow and either squeeze pressure (r = -0.2) or functional outcome (r = 0.31).<br><br>CONCLUSION: This study provides direct anatomical and physiological evidence of one arterial system within the gracilis muscle. It is therefore questionable whether ligation of the minor vascular pedicles is the bottleneck in human dynamic graciloplasty. An additional operation for vascular delay may be redundant. A prospective randomized clinical study should be performed to compare the functional outcome in patients with and without a delay procedure.}, }
@article {pmid9269642, year = {1997}, author = {Burke, SK and Slatopolsky, EA and Goldberg, DI}, title = {RenaGel, a novel calcium- and aluminium-free phosphate binder, inhibits phosphate absorption in normal volunteers.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {12}, number = {8}, pages = {1640-1644}, doi = {10.1093/ndt/12.8.1640}, pmid = {9269642}, issn = {0931-0509}, mesh = {Absorption/drug effects ; Adolescent ; Adult ; Aluminum/analysis ; Calcium/analysis ; Carrier Proteins/adverse effects/chemistry/*pharmacology ; Feces/chemistry ; Female ; Humans ; Male ; Phosphate-Binding Proteins ; Phosphates/*antagonists &amp; inhibitors/pharmacokinetics ; Phosphorus/analysis/urine ; Polyamines/adverse effects/chemistry/*pharmacology ; Reference Values ; Sevelamer ; }, abstract = {BACKGROUND: Available phosphate binders contain aluminium or calcium which can be associated with undesirable effects. RenaGel, cross-linked poly (allylamine hydrochloride), is a non-absorbed phosphate-binding polymer, free of calcium and aluminium. We conducted this study to examine the safety and phosphate binding efficacy of RenaGel in volunteers.<br><br>METHODS: During 18 days (days 0-17) at the clinical study unit, 24 subjects consumed a phosphate-controlled diet designed to provide 37.5 mmol (1200 mg) elemental phosphorus per day. From the morning of day 5 to the morning of day 9, urine and faeces were collected. Average baseline urine and faecal phosphorus contents were determined. On days 9-16, the subjects received either RenaGel 1 g, 2.5 g, or 5 g or placebo three times per day immediately prior to the meals. From the morning of day 13 to the morning of day 17, urine and faeces were again collected and phosphorus contents on treatment were determined.<br><br>RESULTS: RenaGel inhibited dietary phosphate absorption as measured by a decline in average daily urinary phosphorus excretion and an increase in average daily fecal phosphorus excretion. Average urine phosphorus contents on treatment were 27.2 mmol (870 mg) per day in the placebo group vs 23.8 mmol (762 mg), 19.5 mmol (625 mg), and 16.6 mmol (530 mg) per day in the RenaGel 1-g, 2.5-g, and 5-g groups. Average daily faecal phosphorus content on treatment was markedly higher in the RenaGel 5-g group, 19.1 mmol (611 mg) per day vs 10.7 mmol (342 mg) per day for the placebo group. RenaGel also decreased total serum cholesterol by 0.71 mmol/L (27.5 mg/dl), 0.55 mmol/l (21.3 mg/dl), and 1.08 mmol/l (41.8 mg/dl) for the RenaGel 1-g, 2.5-g, and 5-g groups. RenaGel was well tolerated with adverse events similar to placebo.<br><br>CONCLUSIONS: RenaGel is a safe, effective, and well tolerated phosphate binder in normal volunteers. The degree of phosphate binding consistent with its potential use as a phosphate binder in renal failure patients.}, }
@article {pmid9267404, year = {1997}, author = {Christensen, CM}, title = {The effect of three distinct sex ratios at two Oesophagostomum dentatum worm population densities.}, journal = {The Journal of parasitology}, volume = {83}, number = {4}, pages = {636-640}, pmid = {9267404}, issn = {0022-3395}, mesh = {Animals ; Feces/parasitology ; Female ; Fertility ; Intestine, Large/*parasitology ; Male ; Oesophagostomiasis/parasitology/*veterinary ; Oesophagostomum/growth &amp; development/*physiology ; Parasite Egg Count/veterinary ; *Sex Ratio ; Specific Pathogen-Free Organisms ; Swine ; Swine Diseases/*parasitology ; }, abstract = {Helminth-free donor pigs were inoculated with infective larvae of Oesophagostomum dentatum. Five weeks later, the donor pigs were killed to recover the adult worms. By nonsurgical rectal transplantation, 6 groups of helminth-free recipient pigs were then given different female-to-male ratios (FMR) of O. dentatum worms (10% females [F], 50% F, 90% F) at either high (300 worms) or low (30 worms) doses. Fecal egg excretions were measured once weekly following transplantation until the pigs were killed 4 wk posttransplantation to assess the worm burdens and their location. There was a strong and significant correlation between numbers of male and female worms located in the different sections of the large intestine, suggesting that the worm sex as well as physiological factors in the pig intestine may govern the location of the worms. There were no significant differences in fecal egg counts or female worm fecundity between any of the groups. However at the low dose level, the female worm fecundity was markedly lower in the L10% F group than in the 2 other groups, thus suggesting for low worm densities an upper threshold for the FMR above which O. dentatum females produce fewer eggs.}, }
@article {pmid9224315, year = {1997}, author = {al-Ali, M and Kashmoula, D and Saoud, IJ}, title = {Experience with 30 posttraumatic rectourethral fistulas: presentation of posterior transsphincteric anterior rectal wall advancement.}, journal = {The Journal of urology}, volume = {158}, number = {2}, pages = {421-424}, doi = {10.1016/s0022-5347(01)64493-8}, pmid = {9224315}, issn = {0022-5347}, mesh = {Adolescent ; Adult ; Humans ; Male ; Middle Aged ; Rectal Fistula/etiology/*surgery ; Rectum/*injuries ; Surgical Procedures, Operative/methods ; Urethra/*injuries ; Urethral Diseases/etiology/*surgery ; Urinary Diversion/methods ; Urinary Fistula/etiology/*surgery ; }, abstract = {PURPOSE: We present the challenging problems involving the treatment of rectourethral fistulas, especially those caused by war wounds. Various existing techniques used by a single surgeon are compared in this study. The method of posterior transsphincteric anterior rectal wall advancement is described as the treatment of choice. We emphasize the importance of fecal and urinary diversion. To our knowledge this series is the largest in the literature.<br><br>MATERIALS AND METHODS: From 1981 to 1994 we treated 30 men 18 to 50 years old (mean age 34) with posttraumatic rectourethral fistulas, including 23 (76.5%) caused by missiles. Urethroscopy with digital examination under anesthesia was the most reliable diagnostic study. End sigmoid colostomy and suprapubic cystostomy were performed in all patients.<br><br>RESULTS: In 14 patients (46.5%) the fistula healed after double diversion but 16 (53.5%) required reconstruction for repair. Of the 6 procedures using established techniques in 5 patients 3 (50%) failed and 3 were successful but a urethral stricture developed after 2 (66%). On the other hand, in all patients (100%) who underwent repair via posterior transsphincteric anterior rectal wall advancement the fistula resolved and a stricture developed in 3 (27%). Fistula size and extent of fibrosis affected treatment, while etiology did not. Urethral obstruction complicated only the missile wounds.<br><br>CONCLUSIONS: Double diversion has resulted in resolution of approximately half of the small, less fibrous fistulas. Early repair is recommended for large fibrous fistulas. Anterior rectal wall advancement through a posterior transsphincteric incision offers a new option that has proved to be successful and safe, and causes fewer urethral complications. It also provided good visualization with minimal bleeding and was less painful. Double diversion is a prerequisite to reconstruction.}, }
@article {pmid9185745, year = {1997}, author = {Pakarinen, M and Miettinen, TA and Kuusanmäki, P and Vento, P and Kivistö, T and Halttunen, J}, title = {Effect of ileal autotransplantation on cholesterol, bile acids, and biliary lipids in pigs with proximal small bowel resection.}, journal = {Hepatology (Baltimore, Md.)}, volume = {25}, number = {6}, pages = {1315-1322}, doi = {10.1002/hep.510250602}, pmid = {9185745}, issn = {0270-9139}, mesh = {Absorption ; Animals ; Bile/*metabolism ; Bile Acids and Salts/analysis/blood/*metabolism ; Cholesterol/blood/*metabolism ; Feces/chemistry ; Female ; Ileum/*transplantation ; Intestine, Small/*surgery ; *Lipid Metabolism ; Swine ; Transplantation, Autologous ; }, abstract = {Our major aim was to investigate the consequences of ileal autotransplantation in pigs with proximal small intestinal resection on biliary lipids and metabolism of bile acids. Biliary lipid secretion rates and bile acid absorption were assessed by measuring dietary and biliary lipids, fractional cholesterol absorption, and fecal excretion of cholesterol and bile acids. In addition, serum bile acids and cholesterol, biliary and fecal bile acid species, and ileal villus height were determined after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum with systemic venous drainage (n = 15) or transection (n = 5). Autotransplantation further increased fecal excretion of neutral and acidic steroids and serum concentration of bile acids after proximal resection (P < .05 for all); autotransplantation significantly decreased serum cholesterol, ileal villus height, fractional bile acid and cholesterol absorption, and biliary molar percentage of total and primary bile acids, whereas biliary secretion of bile acids, enriched by secondary bile acids, and cholesterol remained unchanged. At 14 weeks, ileal villus height, fractional bile acid and cholesterol absorption, biliary molar percentage of bile acids, and proportion of secondary biliary bile acids were altered by transplantation from the respective postresection values of 864 +/- 22 microm, 97.9 +/- 0.6%, 26.9 +/- 3.9%, 91.8 +/- 1.2% and 9.2 +/- 1.3% to 428 +/- 21 microm, 91.1 +/- 1.5%, 9.5 +/- 1.1%, 83.9 +/- 1.4% and 52.5 +/- 3.5% (P < .005 for all). Posttransplantation biliary bile acid secretion correlated positively with fractional reabsorption (r = .70) and biliary molar percentage (r = .73) of bile acids and ileal villus height (r = .65; P < .01 for all). Decreased absorption efficiency and biliary molar percentage of bile acids, increased biliary secondary bile acids, and short ileal villi point to bacterial overgrowth-induced bile acid malabsorption, which with decreased absorptive area may contribute to malabsorption of other lipids after ileal autotransplantation. Compensatory increase in cholesterol synthesis in the pigs with autotransplanted ileum appeared sufficient for constant biliary secretion of cholesterol and bile acids.}, }
@article {pmid9425691, year = {1997}, author = {Gibson, GE and McGinnity, E and McGrath, P and Carmody, M and Walshe, J and Donohoe, J and O'Moore, R and Murphy, GM}, title = {Cutaneous abnormalities and metabolic disturbance of porphyrins in patients on maintenance haemodialysis.}, journal = {Clinical and experimental dermatology}, volume = {22}, number = {3}, pages = {124-127}, pmid = {9425691}, issn = {0307-6938}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Porphyria Cutanea Tarda/etiology ; Porphyrins/*blood ; Reference Values ; Renal Dialysis/*adverse effects ; Skin Diseases/blood/*etiology ; }, abstract = {Blistering disorders may occur in patients with chronic renal failure. Photoactive medication may account for some, and others may be attributable to porphyria cutanea tarda (PCT), but most appear idiopathic. Seventy haemodialysis patients at the National Renal Transplant Centre were therefore screened to determine the prevalence of cutaneous disease and to establish a reference range for plasma porphyrins in this population. The possible contribution of hepatitis C virus (HCV) infection to increased porphyrin levels in this group was also investigated. Ninety four percent of patients on haemodialysis had dermatoses associated with chronic uraemia, and the plasma porphyrin levels in those patients (mean +/- 2 S.D.: 19.1 +/- 13.5 nmol/L) were significantly higher than those of a normal population (n = 40; mean +/- 2 S.D.: 5.5 +/- 3.2 nmol/L) (p < 0.05). Only 2 patients (2.9%), however, had antibodies to HCV and although three others had blistering on light-exposed skin, none of these had PCT or was on photoactive medication, nor did they differ from the rest of the haemodialysis population with regard to erythropoietin or alcohol ingestion. For patients on haemodialysis, therefore, in whom urinary porphyrin estimation is impossible or unreliable, it is recommended that plasma porphyrin profiles be checked where necessary with reference to the range for a haemodialysis population, in addition to assessment of the faecal porphyrin profile. Abnormal porphyrin levels in this group may not, however, be explained by HCV infection, but the occurrence of blistering on the sun-exposed sites of 3 patients suggests that ultraviolet radiation may be implicated in those instances.}, }
@article {pmid9175050, year = {1997}, author = {Rosenbaum, DP and Holmes-Farley, SR and Mandeville, WH and Pitruzzello, M and Goldberg, DI}, title = {Effect of RenaGel, a non-absorbable, cross-linked, polymeric phosphate binder, on urinary phosphorus excretion in rats.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {12}, number = {5}, pages = {961-964}, doi = {10.1093/ndt/12.5.961}, pmid = {9175050}, issn = {0931-0509}, mesh = {Absorption ; Animals ; Female ; Gels ; Humans ; In Vitro Techniques ; Kidney Failure, Chronic/drug therapy/metabolism ; Phosphates/metabolism ; Phosphorus/blood/*urine ; Phosphorus, Dietary/administration &amp; dosage/pharmacokinetics ; Polyamines/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Sevelamer ; }, abstract = {BACKGROUND: Normalization of serum phosphorus is critical in the treatment of End Stage Renal Failure patients. Aluminum or calcium based phosphate binders, while efficacious, are associated with potential adverse side effects and toxicities. We have developed RenaGel, a novel, non-absorbed hydrogel which binds dietary phosphate leading to increased fecal excretion, decreased absorption and decreased serum phosphorus levels. In this paper, we present results from both in vitro and in vivo studies in which we examined the efficacy of this novel phosphate binder.<br><br>METHODS: In vitro, RenaGel was suspended in the test solution, and the mixture was stirred for 1 hour at room temperature. The solid was then filtered off, and the residual liquid analyzed for phosphate. In vivo, RenaGel was mixed in rodent feed at different concentrations and fed to normal rats for up to 4 days. Urine was collected and analysed for phosphate content.<br><br>RESULTS AND CONCLUSIONS: In vitro binding studies demonstrate that RenaGel has an extremely high phosphate binding capacity. At an estimated physiological concentration of 5 mM phosphate, RenaGel binds 2.6 mmole phosphate/g of phosphate binder. The in vivo binding study shows that RenaGel mixed into the diet decreased urinary phosphorus excretion in a dose dependent manner. RenaGel particles with a 23 microns mean diameter are more efficacious than the larger ones. In conclusion, the above studies indicate that RenaGel is a potent phosphate binder. RenaGel contains no calcium or aluminum and offers an alternative to existing phosphate binder treatments.}, }
@article {pmid9180383, year = {1997}, author = {Thompson, J and Zamboni, WC and Cheshire, PJ and Richmond, L and Luo, X and Houghton, JA and Stewart, CF and Houghton, PJ}, title = {Efficacy of oral irinotecan against neuroblastoma xenografts.}, journal = {Anti-cancer drugs}, volume = {8}, number = {4}, pages = {313-322}, doi = {10.1097/00001813-199704000-00002}, pmid = {9180383}, issn = {0959-4973}, support = {CA21675/CA/NCI NIH HHS/United States ; CA23099/CA/NCI NIH HHS/United States ; CA32613/CA/NCI NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Antineoplastic Agents, Phytogenic/*pharmacology ; Camptothecin/*analogs &amp; derivatives/pharmacology ; Child, Preschool ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Enzyme Inhibitors/*pharmacology ; Female ; Humans ; Infant ; Irinotecan ; Mice ; Mice, Inbred CBA ; Neuroblastoma/*drug therapy/enzymology ; Topoisomerase I Inhibitors ; Transplantation, Heterologous ; }, abstract = {The efficacy of the topoisomerase I inhibitor, 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptotheci n (irinotecan, CPT-11), administered by oral gavage has been examined against a panel of six independently derived neuroblastoma xenografts. Irinotecan was administered either daily for 5 days on 12 consecutive weeks ¿(d x 5)12¿ or for 5 days on two consecutive weeks repeated every 21 days for 4 cycles ¿[(d x 5)2]4¿. Given on the (d x 5)12 schedule the maximum tolerated dose (MTD) was 50 mg/kg. For intermittent scheduling ¿[(d x 5)2]4¿, the MTD was 75 mg/kg, resulting in the same total dose being administered (3 g/kg) over the period of treatment. At the MTD for the 12 consecutive week schedule there were two of 42 toxicity related deaths, whereas intermittent scheduling at the MTD resulted in none of 42 deaths. The intermittent schedule ¿[(d x 5)2]4¿ was less toxic than therapy given (d x 5)12, as at the end of treatment mice weighed 92 +/- 4% (SD; n = 6 experiments) and 81 +/- 4% (SD; n = 6 experiments) of their body weight at the start of therapy, respectively. The latter schedule was associated with loose feces starting around week 8 of therapy, broken teeth and a high incidence of swelling of the orbital conjunctiva that developed late in the course of therapy. Given (d x 5)12, irinotecan caused complete regressions of all six neuroblastoma xenograft lines. Because mice tolerate significantly greater systemic exposure to SN-38 lactone than do patients (as determined by plasma AUC at the respective MTD), we evaluated the intermittent schedule of administration, reducing the dose/administration to determine the lowest dose levels that produced objective regressions of these neuroblastoma xenografts and determined the daily systemic exposure associated with these dose levels. In four lines examined objective responses were obtained at dose levels of 12.5 or 6.25 mg/kg. The daily plasma AUC exposures associated with minimum dose achieving response in NB1691 (12.5 mg/kg), NB1643 (6.25 mg/kg) and NBEB (12.5 mg/kg) for irinotecan lactone were 219, 152 and 653 ng-h/ml, respectively; and for SN-38 lactone were 704, 418 and 987 ng-h/ml, respectively. These results indicate that childhood neuroblastoma xenografts are highly sensitive to irinotecan given by oral administration and therapeutic activity is similar to i.v. irinotecan administered on similar schedules.}, }
@article {pmid9092747, year = {1997}, author = {Fritsch, C and Bolsen, K and Ruzicka, T and Goerz, G}, title = {Congenital erythropoietic porphyria.}, journal = {Journal of the American Academy of Dermatology}, volume = {36}, number = {4}, pages = {594-610}, doi = {10.1016/s0190-9622(97)70249-4}, pmid = {9092747}, issn = {0190-9622}, mesh = {Adult ; Coproporphyrins/analysis ; Erythrocytes/chemistry ; Female ; Humans ; Male ; Middle Aged ; *Porphyria, Erythropoietic/complications/metabolism/pathology/therapy ; Uroporphyrinogen Decarboxylase/metabolism ; Uroporphyrinogen III Synthetase/genetics ; Uroporphyrins/analysis ; }, abstract = {Congenital erythropoietic porphyria is a rare autosomal-recessive disorder of the porphyrin metabolism caused by the homozygous defect of uroporphyrinogen III cosynthase. High amounts of uroporphyrin I accumulate in all cells and tissues, reflected by an increased erythrocyte porphyrin concentration and excretion of high porphyrin amounts in urine and feces. Dermal deposits of uroporphyrin frequently induce a dramatic phototoxic oxygen-dependent skin damage with extensive ulcerations and mutilations. Splenomegaly and hemolytic anemia are typical internal symptoms. Skeletal changes such as osteolysis and calcifications are frequent. To date 130 cases of congenital erythropoietic porphyria have been published and are summarized here. Splenectomy, erythrocyte transfusions, and bone marrow transplantation have shown some beneficial effect. The best therapy is the avoidance of sunlight. In the two patients with congenital erythropoietic porphyria described here, oral administration of the oxygen quenchers ascorbic acid and alpha-tocopherol resulted in an improvement in the reduced hemoglobin and erythrocyte concentrations.}, }
@article {pmid9117209, year = {1997}, author = {Singh, G and Thomas, DG}, title = {Bowel problems after enterocystoplasty.}, journal = {British journal of urology}, volume = {79}, number = {3}, pages = {328-332}, doi = {10.1046/j.1464-410x.1997.03274.x}, pmid = {9117209}, issn = {0007-1331}, mesh = {Adolescent ; Adult ; Cecum/transplantation ; Colon, Sigmoid/transplantation ; Constipation/*etiology/therapy ; Diarrhea/*etiology/therapy ; Fecal Incontinence/*etiology/therapy ; Humans ; Ileum/transplantation ; Middle Aged ; Postoperative Complications/*etiology ; Time Factors ; Urinary Bladder/*surgery ; Urinary Bladder Diseases/*surgery ; Urinary Bladder, Neurogenic/surgery ; }, abstract = {OBJECTIVES: To document the changes in bowel habit in patients who have undergone enterocystoplasty.<br><br>PATIENTS AND METHODS: Sixty-nine patients with neuropathic (NP) and 44 with non-neuropathic (NNP) bladder dysfunction (mean age 26 years, range 13-61, 93.6% socially continent), followed for at least 36 months after cystoplasty, were assessed using a questionnaire addressing faecal frequency, consistency, method of evacuation and incontinence episodes before and after surgery.<br><br>RESULTS: Of the patients with NP bladder dysfunction, 26 (38%) had more and seven (10%) less frequent bowel action after surgery, with 36 (52%) unchanged; 38 (55%) of patients had unchanged consistency, 26 (38%) were looser and five (7%) more constipated; 41 (59%) opened their bowels as before, 16 (23%) needed more help and 12 (17%) less help to evacuate; 16 (23%) patients had more and 17 (25%) less episodes of incontinence; 21 (30%) patients felt their bowels had not become normal after their operation and only 24 (35%) that they had returned to normal within 3 months of their operation. The bowel segment used was ileum in 44 patients, ileocaecal in 11 and sigmoid cystoplasty in 14. Patients with intact ileum did not have the same degree of diarrhoea, with only three of the 14 patients with a sigmoid cystoplasty being adversely affected. Of the patients with NNP bladder dysfunction, 18 patients (41%) had a more and five (11%) a less frequent bowel action; 20 (46%) had more loose and five (11%) less loose bowel action; similar numbers (five and four) needed either an increase or a decrease in laxatives or enemata: surprisingly, 12 patients (27%) felt they had an increase in the episodes of incontinence; 17 (39%) patients felt their bowels returned to normal within 3 months of surgery and 30% felt their bowels had not become normal after surgery. Only one patient in this group had a sigmoid cystoplasty and she did not find that the operation interfered with her bowel function.<br><br>CONCLUSIONS: Ileal resection results in malabsorption of bile acids, maldigestion of fat and an imbalance of water and electrolytes. Patients with neurogenic bladders are finely balanced between acceptable bowel function and choas, and surgery often tips this balance the wrong way. In 30% of the present patients, bowel problems persisted after surgery, with 38% having increased frequency. 38% having looser consistency and 23% more incontinence episodes following surgery. More surprisingly, a high percentage of NNP patients had bowel problems after cystoplasty.}, }
@article {pmid9612750, year = {1997}, author = {Delmont, J and Igo-Kemenes, A and Peyron, F and Ruiz, JM and Moreau, J and Bourgeade, A}, title = {[Immunocompromised travelers].}, journal = {Medecine tropicale : revue du Corps de sante colonial}, volume = {57}, number = {4 Bis}, pages = {452-456}, pmid = {9612750}, issn = {0025-682X}, mesh = {*Counseling ; Humans ; Hygiene ; *Immunocompromised Host ; Malaria/prevention &amp; control ; *Patient Education as Topic ; Risk Factors ; *Travel ; Vaccination ; }, abstract = {More and more immunocompromised people travel abroad especially in tropical countries where infectious risks are high. Before leaving, these subjects must consult their general practitioner who will determine their fitness in function of type of immunodeficiency, travel destination, availability of medical care at the destination, and possibility of medical evacuation. Counseling should also be provided concerning the precautions necessary to avoid the hazards of exposure to fecal material, venereal disease, insect bites, and sun. Antimalarial drug prophylaxis is the same as for uncompromised subjects. Advising immunocompromised subjects about vaccinations is difficult since there is no consensus on the subject. Administration of inert vaccines is usually recommended but their effectiveness is often diminished and harmful effects have been observed in HIV-infected subjects. Administration of live vaccines is always contraindicated in severely immunocompromised subjects but some live vaccines can be used in moderately immunocompromised subjects. The guidelines for vaccination differ depending on the underlying cause of immunodeficiency: congenital defects, cancer, hemopathy, treatment with immunosuppressors or corticosteroids (transplant patients and patients with systemic disease), HIV-infection, or spleen dysfunction. If there is a high risk of contracting a disease for which vaccination is contraindicated, drug prophylaxis or administration of immunoglobulins can be an alternative. If not, travel should either be postponed or the destination should be changed.}, }
@article {pmid9443611, year = {1997}, author = {Ahmed, AE and Jacob, S and Giovanella, BC and Kozielski, AJ and Liehr, JG and Stehlin, JS}, title = {Comparative disposition of the antineoplastic agent 9-nitrocampotothecin and the inactive isomer 12-nitro camptothecin in CASE-bearing nude mice: effect of route of administration on tissue distribution.}, journal = {Cancer chemotherapy and pharmacology}, volume = {41}, number = {1}, pages = {29-36}, doi = {10.1007/s002800050704}, pmid = {9443611}, issn = {0344-5704}, mesh = {Animals ; Antineoplastic Agents, Phytogenic/administration &amp; dosage/*pharmacokinetics ; Autoradiography ; Camptothecin/administration &amp; dosage/*analogs &amp; derivatives/pharmacokinetics ; Infusions, Intravenous ; Injections, Intramuscular ; Isomerism ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms/*metabolism/pathology ; Tissue Distribution ; Tritium/administration &amp; dosage ; }, abstract = {PURPOSE: 9-Nitrocamptothecin (9-NC) and 12-nitrocamptothecin (12-NC) are synthetic structural analogues of camptothecin (CPT) which have been prepared to explore the structure/activity relationship of this group of compounds against a wide variety of experimental tumors. As part of our investigation of the pharmacology and the mechanism of tumor inhibition of these compounds, we examined the effect of route of administration on the distribution of tritium-labeled 9-NC and 12-NC, an active and a poor chemotherapeutic agent, respectively.<br><br>METHODS: Quantitative whole-body autoradiography was used and our results were compared with previous results obtained with the parent compound CPT.<br><br>RESULTS: These studies revealed that, independent of the route of administration, both CPT derivatives were rapidly distributed to gall bladder, gastrointestinal tract and kidney. The excretion from these organs was indicated by the high levels of radioactivity in urine (urinary bladder) and feces (large intestines). The studies also indicated that the distributions of 9-NC and 12-NC were qualitatively similar, but quantitatively higher uptake of radioactivity was observed in animals treated with 12-NC than in those treated with 9-NC at 30 min following treatment. With the exception of the late sampling time (12 h after administration), the accumulation of radioactivity in the lungs (bronchioles) of animals that received an intravenous (i.v.) dose of 9-NC or 12-NC was higher than those treated with an intramuscular (i.m.) dose. However, the retention of drug-derived radioactivity in the tumors of mice treated with an i.m. dose of 9-NC was higher than that in the tumors of i.v.-treated animals and was also higher than that in tumors of animals treated with 12-NC.<br><br>CONCLUSIONS: These results suggest that higher accumulation of 9-NC in tumor tissues than of 12-NC may contribute to the more potent chemotherapeutic activity of the former agent. Our results also suggest that i.m. injection is a more effective route of administration than i.v. administration.}, }
@article {pmid9428116, year = {1997}, author = {Barkholt, LM and Andersson, J and Ericzon, BG and Palmgren, AC and Broomé, U and Duraj, F and Bergquist, A and Herlenius, G and Nord, CE}, title = {Stool cultures obtained before liver transplantation are useful for choice of perioperative antibiotic prophylaxis.}, journal = {Transplant international : official journal of the European Society for Organ Transplantation}, volume = {10}, number = {6}, pages = {432-438}, doi = {10.1007/s001470050082}, pmid = {9428116}, issn = {0934-0874}, mesh = {Adult ; Ampicillin/*therapeutic use ; Ampicillin Resistance ; *Antibiotic Prophylaxis ; Bacterial Infections/blood/prevention &amp; control/urine ; Cholangitis/etiology/microbiology ; Disease Susceptibility/etiology/microbiology/therapy ; Drug Resistance, Multiple ; Enterobacteriaceae/drug effects/isolation &amp; purification ; Feces/*microbiology ; Female ; Fever/drug therapy/etiology/microbiology ; Gentamicins/*therapeutic use ; Humans ; Liver Transplantation/*adverse effects ; Male ; Postoperative Complications/drug therapy/etiology/microbiology ; Prospective Studies ; Risk Factors ; Time Factors ; }, abstract = {Bacterial infections, especially cholangitis, are still common complications after liver transplantation (LTx). During recent years, multiresistant enterococci have become a nosocomial problem in transplant units. The present prospective study on 26 patients, including 24 patients with chronic liver disease, demonstrated that enterococci were the predominant micro-organism involved in post-LTx bacterial infections. They were cultured in the feces and in other sites of 10 out of 13 (77%) patients who underwent extensive examinations. Ampicillin-resistant Enterococcus faecium strains were isolated in urine or feces of 2 of the 13 patients prior to LTx. Similarly, resistance to ampicillin and gentamicin, the empirically used antibiotics for patients with fever of unknown origin, was found in E. faecium strains in 3 and 2 patients, respectively. Moreover, multiresistant E. faecium and E. faecalis strains were demonstrated in 46% of the patients in the postoperative period (3 months). However, no vancomycin-resistant enterococci were isolated. The use of antibiotics within 4 months prior to LTx significantly increased the risk of developing ampicillin-resistant bacteria at the time of LTx and of infections with bacteria of enteric origin after LTx (P = 0.03 and 0.01, respectively). We conclude that stool and urine cultures performed prior to LTX may be useful for selecting prophylactic antibiotic regimens.}, }
@article {pmid9413073, year = {1997}, author = {Rab, M and Mader, N and Kamolz, LP and Hausner, T and Gruber, H and Girsch, W}, title = {Basic anatomical investigation of semitendinosus and the long head of biceps femoris muscle for their possible use in electrically stimulated neosphincter formation.}, journal = {Surgical and radiologic anatomy : SRA}, volume = {19}, number = {5}, pages = {287-291}, doi = {10.1007/BF01637592}, pmid = {9413073}, issn = {0930-1038}, mesh = {Anal Canal/surgery ; Cadaver ; Fecal Incontinence/surgery ; Female ; Humans ; Leg/*anatomy &amp; histology/blood supply/innervation ; Male ; Muscle, Skeletal/*anatomy &amp; histology/blood supply/innervation/transplantation ; }, abstract = {Anal neosphincter formation with electrically stimulated gracilis muscle is used increasingly for the surgical treatment of fecal incontinence. An alternative to gracilis might be of interest if this muscle is not available. 30 semitendinosus muscles and 15 long heads of biceps femoris were investigated on human cadavers. In particular, the nerve and vascular supply of these muscles was studied, both representing basic factors for muscle transposition. The long head of biceps femoris m. was found to receive its dominant vascular supply from the first and second perforating artery and its nerve supply from one motor branch out of the sciatic nerve, both as described in literature. The examination of semitendinosus m., however, revealed new anatomical aspects in its vascular supply. In all cases semitendinosus m. was found to receive dominant vascular pedicles from the medial circumflex femoral artery close to the ischial tuberosity and the second perforating artery. The nerve supply consisted of two motor branches out of the sciatic nerve. Both muscles fulfilled several basic criterias for transposition to the anus. However, regarding these requirements, semitendinosus offered distinct advantages in comparison with the long head of biceps femoris. Due to its vascular and nerve topography, semitendinosus seems suitable to serve as an alternative to gracilis.}, }
@article {pmid9401848, year = {1997}, author = {Altomare, DF and Rinaldi, M and Pannarale, OC and Memeo, V}, title = {Electrostimulated gracilis neosphincter for faecal incontinence and in total anorectal reconstruction: still an experimental procedure?.}, journal = {International journal of colorectal disease}, volume = {12}, number = {5}, pages = {308-312}, doi = {10.1007/s003840050112}, pmid = {9401848}, issn = {0179-1958}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/physiopathology/surgery ; Electric Stimulation ; Fecal Incontinence/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Middle Aged ; Muscle, Skeletal/*transplantation ; Postoperative Complications ; Pressure ; Plastic Surgery Procedures/*methods ; Rectum/physiopathology/surgery ; *Thigh ; Treatment Outcome ; }, abstract = {The possibility of converting an easily fatiguable muscle like the gracilis muscle into a fatigue-resistant one using chronic electrostimulation has renewed interest in Pickrell's procedure. Between July 1991 and June 1996, 9 patients (2 M; 7 F) mean age = 45 y (range 14-72) underwent dynamic graciloplasty using Medtronic electrostimulators. Five patients had faecal incontinence (2 congenitally anomaly, 1 neurological, 2 post-operative) and 4 had a perineal colostomy performed either simultaneously (two cases) or at 3 to 4 years after abdominoperineal excision of the rectum. Early post-operative complications included distal tendon necrosis [1], perineal colostomy breakdown [1], detachment of the gracilis tendon [2] and seroma in the thigh [1]. Long-term complications included rectocele with faecal impaction in one patient with imperforate anus, anal stricture in one patient who had refashioning of a perineal colostomy, and displacement of the lead from the main nerve in 3 with external expulsion in 2. The patient with anal stricture was successfully treated with anoplasty but subsequently returned to an abdominal colostomy due to stricture recurrence 2 years later. The rectocele was successfully treated using a transvaginal approach. Electrical conversion of the muscle was completed in all patients but long term functional results are available for only 5 cases. Manometry revealed a significant improvement in anal pressure under electro-stimulation and the continence grading scale score significantly improved in 4 patients. The technique is applicable to a very selected group of patients with no other options but is still in the experimental phase and should not be performed outside controlled trials. Repeated hospitalisation and reoperations are often required although the complication rate may diminish and improve with experience.}, }
@article {pmid9204849, year = {1997}, author = {Woolner, B}, title = {Biofeedback reeducation in gracilis muscle transposition after rectal trauma: a case presentation.}, journal = {Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society}, volume = {24}, number = {1}, pages = {38-50}, doi = {10.1016/s1071-5754(97)90047-4}, pmid = {9204849}, issn = {1071-5754}, mesh = {Adult ; Biofeedback, Psychology/*methods ; Electromyography ; Exercise Therapy/*methods ; Fecal Incontinence/etiology/*rehabilitation ; Humans ; Male ; Rectum/*injuries/*surgery ; Surgical Flaps/*rehabilitation ; }, abstract = {A 20-year-old male patient had a significant rectal trauma and underwent colostomy and subsequent creation of a neosphincter through gracilis muscle transposition. The patient was referred for biofeedback training to learn to use the transplanted gracilis muscle as a substitute for the external anal sphincter, Through a period of 10 weeks, the patient became able to identify this transplanted muscle and to increase the amplitude and duration of contraction as measured by surface electromyography. Further, resting tone of the neosphincter was increased. The patient gained continence with respect to liquid, gaseous, and solid stool within 26 weeks of the first biofeedback muscle training session.}, }
@article {pmid9041537, year = {1997}, author = {Ok, UZ and Cirit, M and Uner, A and Ok, E and Akçiçek, F and Başçi, A and Ozcel, MA}, title = {Cryptosporidiosis and blastocystosis in renal transplant recipients.}, journal = {Nephron}, volume = {75}, number = {2}, pages = {171-174}, doi = {10.1159/000189527}, pmid = {9041537}, issn = {1660-8151}, mesh = {Adolescent ; Adult ; Animals ; Blastocystis Infections/epidemiology/*etiology ; *Blastocystis hominis ; Cryptosporidiosis/epidemiology/*etiology ; *Cryptosporidium ; Feces/parasitology ; Humans ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Prevalence ; }, abstract = {Some intestinal parasitic infections are frequently seen in renal transplant recipients. Parasites such as Cryptosporidium spp. and Blastocystis hominis are often asymptomatic or responsible for limited infections in normals, but may cause prolonged and heavy infections with gastrointestinal complaints, mainly diarrhea, in immunocompromised patients. Such infections can often not be detected by routine diagnostic procedures, but special concentration and staining methods are needed. We investigated 115 fecal specimens from 69 renal transplant recipients and 42 fecal specimens from 42 control cases. Of the 69 recipients, 27 (39.1%) had B. hominis and 13 (18.8%) had Cryptosporidium spp. in at least one fecal specimen. Prevalence of symptomatic Cryptosporidium infections was significantly higher in the renal transplant recipients, when compared with the control group (p < 0.05). Special parasitological procedures must be performed in immunocompromised patients with chronic gastrointestinal complaints. Disappearance of symptoms after antiparastic drugs in some of 16 symptomatic patients are described, suggesting that these infections are more pathogenic in transplant recipients.}, }
@article {pmid9039691, year = {1997}, author = {García-Llamazares, JL and Alvarez-de-Felipe, AI and Redondo-Cardeña, P and Voces-Alonso, JA and Prieto-Fernández, JG}, title = {In vivo inhibition of the regenerative capacity of hydatid material after treatment with netobimin.}, journal = {Parasitology research}, volume = {83}, number = {2}, pages = {105-108}, doi = {10.1007/s004360050219}, pmid = {9039691}, issn = {0932-0113}, mesh = {Animals ; Anthelmintics/*pharmacology ; Echinococcosis/pathology/*prevention &amp; control/transmission ; Echinococcus/drug effects/*growth &amp; development ; Feces/parasitology ; Fenbendazole/*pharmacology ; Gerbillinae ; Guanidines/*pharmacology ; Mice ; Recurrence ; Sheep ; }, abstract = {The effect of netobimin and netobimin plus fenbendazole administration on secondary hydatid disease was studied. Secondary hydatid disease in gerbils (Meriones unguiculatus) was produced by intraperitoneal inoculation of protoscolices of Echinococcus granulosus. The experimental animals received doses of 20 and 50 mg/kg of netobimin or a mixture of netobimin and 1.7 mg/kg of fenbendazole. The results showed that after a single dose of netobimin at the studied concentrations, the cystic material transplanted into the mouse produced a significant recurrence of the disease, but the most remarkable finding was that the hydatid-cyst recurrence never took place when netobimin was given together with fenbendazole.}, }
@article {pmid9027808, year = {1997}, author = {Korzets, A and Gepstein, R and Ori, Y and Chagnac, A and Weinstein, T and Herman, M and Zevin, D and Gafter, U}, title = {Quadriparesis and faecal incontinence in a long-term haemodialysis patient.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {12}, number = {1}, pages = {224-225}, doi = {10.1093/ndt/12.1.224}, pmid = {9027808}, issn = {0931-0509}, mesh = {Amyloidosis/etiology/metabolism ; Fecal Incontinence/*etiology ; Humans ; Male ; Middle Aged ; Paresis/*etiology ; Renal Dialysis/*adverse effects ; Spinal Diseases/diagnostic imaging/etiology ; Tomography, X-Ray Computed ; beta 2-Microglobulin/metabolism ; }, }
@article {pmid9027787, year = {1997}, author = {Fabrizi, F and Lunghi, G and Bacchini, G and Corti, M and Pagano, A and Locatelli, F}, title = {Hepatitis E virus infection in haemodialysis patients: a seroepidemiological survey.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {12}, number = {1}, pages = {133-136}, doi = {10.1093/ndt/12.1.133}, pmid = {9027787}, issn = {0931-0509}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Epidemiologic Factors ; Female ; Hepatitis Antibodies/blood ; Hepatitis E/*epidemiology/immunology/transmission ; Hepatitis E virus/immunology ; Humans ; Immunoglobulin G/blood ; Italy/epidemiology ; Male ; Middle Aged ; Renal Dialysis/*adverse effects ; Risk Factors ; Seroepidemiologic Studies ; }, abstract = {BACKGROUND: Hepatitis E virus (HEV) is the causative agent for enteric non-A, non-B hepatitis. Transmission is via the faecal route but the possibility of transmission by blood has been raised. Data concerning anti-HEV prevalence among chronic haemodialysis (HD) patients are few and give conflicting results.<br><br>METHODS: We tested for anti-HEV antibody 204 chronic HD patients attending a single dialysis unit. A specific solid-phase enzyme-linked immunoassay (Abbott HEV EIA) was used.<br><br>RESULTS: We found six anti-HEV-positive patients, the anti-HEV prevalence was 3% (95% CI 0-6%). The prevalence rates of HBV and HCV infections were 39% (31-45%) and 22% (16-28%) respectively. No anti-HEV-positive patient showed past or current biochemical signs of liver damage. One of six (17%) anti-HEV-positive patients was an immigrant; no risk factor for anti-HEV antibody was identified in the other anti-HEV-positive individuals.<br><br>CONCLUSIONS: We observed a low anti-HEV prevalence: there was no association between HEV and blood-borne infections (HBV, HCV, and HIV) in our HD patients; most anti-HEV-positive patients we found were probably related to a local infection by HEV. This is one of the first reports concerning seroepidemiology of HEV infection in a large cohort of chronic HD individuals.}, }
@article {pmid8968225, year = {1996}, author = {Mander, BJ and Abercrombie, JF and George, BD and Williams, NS}, title = {The electrically stimulated gracilis neosphincter incorporated as part of total anorectal reconstruction after abdominoperineal excision of the rectum.}, journal = {Annals of surgery}, volume = {224}, number = {6}, pages = {702-9; discussion 709-11}, pmid = {8968225}, issn = {0003-4932}, mesh = {Aged ; Anal Canal/*physiopathology ; *Electric Stimulation Therapy ; Feasibility Studies ; Fecal Incontinence/physiopathology/*therapy ; Female ; Humans ; Male ; Middle Aged ; Muscles/transplantation ; Rectum/*surgery ; Treatment Outcome ; }, abstract = {OBJECTIVE: The authors investigated the feasibility and effectiveness of combining electrically stimulated gracilis neoanal (ESGN) sphincter and a coloperineal anastomosis in selected patients after abdominoperineal excision of the rectum (APER).<br><br>SUMMARY BACKGROUND DATA: The ESGN is effective in the treatment of idiopathic fecal incontinence.<br><br>METHODS: Between March 1989 and September 1993, 12 patients (9 men, 3 women) with a median age of 59.25 years (range, 45-70) underwent the procedure. The underlying disease was adenocarcinoma in 10, anal malignant melanoma in 1, and a sweat gland tumor in the other. In all patients, a sphincter saving resection was contraindicated. The procedure was performed in stages. Stage 1 involved a conventional APER with the formation of a perineal stoma. Eleven patients underwent a vascular delay procedure. All patients were defunctioned. In stage 2, the gracilis was mobilized, transposed around the anal canal, and the electrodes and hardware needed for electrical stimulation were implanted. Once muscle conversion was complete, the defunctioning stoma was closed.<br><br>RESULTS: Eight patients were closed successfully. In seven of the eight patients, complete physiologic measurements were taken. Median basal and maximum neosphincter pressures were 30 and 122 cm H2O, respectively, at the start of electrical stimulation and 22.5 and 76.2 cm H2O, respectively, after 1 year. Median functioning neosphincter pressure was 36 cm H2O at 1 year. All of the patients whose stomas were closed experienced episodes of incontinence to solid stool and wore pads for persistent fecal soiling. They all reported difficulty in evacuation. Despite imperfect continence, no patient wished to go back to life with a stoma.<br><br>CONCLUSIONS: The incorporation of ESGN as part of total anorectal reconstruction is technically feasible. The majority of patients are satisfied with their function and pleased to avoid a permanent stoma.}, }
@article {pmid8943114, year = {1996}, author = {Shafik, A}, title = {Pectinatoplasty: a technique for treatment of sensory fecal incontinence.}, journal = {Journal of pediatric surgery}, volume = {31}, number = {11}, pages = {1520-1523}, doi = {10.1016/s0022-3468(96)90169-4}, pmid = {8943114}, issn = {0022-3468}, mesh = {Child ; Child, Preschool ; Fecal Incontinence/*surgery ; Female ; Humans ; Intestinal Mucosa/*transplantation ; Male ; Patient Selection ; Rectum/abnormalities/*innervation/surgery ; Sensation Disorders/physiopathology/*surgery ; Surgical Flaps/*methods ; Wound Healing ; }, abstract = {Nineteen patients (12 boys, 7 girls; mean age, 6.2 +/- 1.6 SD years) had fecal incontinence owing to absence of the ectodermal lining of the lower rectal neck. Physical examination findings were normal. The anal mucosa extended to the anal verge and was insensitive; there was no ectodermal lining or pectinate line in the lower rectal neck. The 19 patients were selected from a group of 62 patients with anorectal agenesis who had undergone an abdominoanal pull-through operation. The criterion for inclusion in the study was normal anorectal physiology. "Pectinatoplasty" was carried out with the patient under local anesthesia. Two 1.5- x 1.5-cm cutaneous flaps from each of the 5 and 12 o'clock positions of the perianal skin were advanced into the lower rectal neck at the site of an excised mucosal patch of similar size. The patients were discharged on the day of operation. Sixteen patients became continent. Two patients did not improve because of dislocation of the cutaneous flaps outside the anal orifice, as a result of suturing under tension; they became continent after regrafting, using two lateral flaps placed at the 3 and 9 o'clock positions. One patient had anal stenosis and was subjected to dilatation. Pectinatoplasty proved successful in restoring fecal continence in patients who lacked ectodermal anal lining. The procedure is simple, easy, and can be performed on an outpatient basis.}, }
@article {pmid8916408, year = {1996}, author = {Christensen, CM and Grøndahl-Nielsen, C and Nansen, P}, title = {Non-surgical transplantation of Oesophagostomum dentatum to recipient pigs via rectal intubation.}, journal = {Veterinary parasitology}, volume = {65}, number = {1-2}, pages = {139-145}, doi = {10.1016/0304-4017(95)00935-3}, pmid = {8916408}, issn = {0304-4017}, mesh = {Animals ; Female ; Intestine, Large/parasitology ; Male ; Parasite Egg Count ; Rectum/parasitology ; Sheep ; *Sheep Diseases ; Strongylida Infections/transmission/*veterinary ; *Strongyloidea/isolation &amp; purification ; }, abstract = {This experimental was designed to evaluate a new transplantation method, which employs a non-invasive rather than a surgical technique for transplanting Oesophagostomum dentatum worms to recipient pigs. Four groups of pigs were used. Group A (four pigs) served as a donor group, and these pigs were each inoculated with 6000 L3 of O. dentatum. Groups B, C, and D (five pigs each) served as helminth naive recipient pigs. On Day 28 post inoculation, the donor pigs were slaughtered, and the worms recovered by an agar-gel technique. Within 3-4 h after slaughter of the donor animals, a mean of 357 worms (male/female = 1.0) were transferred to each of the sedated recipient pigs via a PVC tube inserted approximately 50 cm up into the rectum and colon descendens. The infection was then monitored by weekly faecal egg counts and by killing the recipient pigs at Week 1 (group B), Week 2 (group C), and Week 3 (group D) post transplantation. The majority of the recovered worms were found in the proximal third of the colon, i.e., the normal predilection site of O. dentatum. The mean worm recovery for groups B and D was 85%, whereas from group C it was only 23%. The faecal egg counts were positive throughout the experiment, although low in group C at the time of slaughter 2 weeks post transplantation. The male/female ratios changed from an initial 1.0 to 1.5 group C, whereas there was little or no change in groups B and D. The reason for the deviating results in group C are obscure. This method is less traumatic to animals when compared with surgical transfer techniques, is rapid to perform, and will allow studies on a larger scale.}, }
@article {pmid8955737, year = {1996}, author = {Cariem, AK and Arendse, M and Cruse, P and Rayner, B}, title = {A 34-year-old man with recurrent melaena after renal transplantation.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {86}, number = {10}, pages = {1284-1288}, pmid = {8955737}, issn = {0256-9574}, mesh = {Adult ; Azathioprine/therapeutic use ; Diagnosis, Differential ; *Gastrointestinal Hemorrhage/diagnosis/drug therapy/etiology/physiopathology/surgery ; Humans ; Immunosuppressive Agents/therapeutic use ; Kidney Failure, Chronic/complications/physiopathology ; *Kidney Transplantation ; *Melena/drug therapy/etiology ; Recurrence ; Renal Dialysis ; Steroids/therapeutic use ; Tuberculosis, Gastrointestinal/complications/drug therapy/physiopathology ; Uremia/complications/physiopathology ; }, }
@article {pmid8907953, year = {1996}, author = {Pakarinen, M and Halttunen, J and Kuusanmäki, P and Raivio, P and Kivistö, T and Miettinen, TA}, title = {Increased fecal excretion of bile acids after ileal transplantation in the pig.}, journal = {Transplantation proceedings}, volume = {28}, number = {5}, pages = {2564-2565}, pmid = {8907953}, issn = {0041-1345}, mesh = {Animals ; Bile Acids and Salts/analysis/*metabolism ; Cholesterol/blood ; Feces ; Female ; Gastrointestinal Transit ; Ileum/physiology/*transplantation ; Intestinal Absorption ; Sterols/analysis ; Swine ; Transplantation, Autologous/*physiology ; }, }
@article {pmid8976659, year = {1996}, author = {Papadopoulou, A and Lloyd, DR and Williams, MD and Darbyshire, PJ and Booth, IW}, title = {Gastrointestinal and nutritional sequelae of bone marrow transplantation.}, journal = {Archives of disease in childhood}, volume = {75}, number = {3}, pages = {208-213}, pmid = {8976659}, issn = {1468-2044}, mesh = {Bone Marrow Transplantation/*adverse effects ; Celiac Disease/complications/etiology ; Child ; Diarrhea/complications/etiology ; Exocrine Pancreatic Insufficiency/complications ; Female ; Gastrointestinal Diseases/*etiology ; Graft vs Host Disease/complications ; Humans ; Male ; Nutritional Status ; Parenteral Nutrition/adverse effects ; Prospective Studies ; Protein-Losing Enteropathies/complications ; Serum Albumin/analysis ; }, abstract = {The nature of the gastrointestinal injury following bone marrow transplantation and its clinical and nutritional sequelae are poorly defined. Prospective assessments of gastrointestinal function, nutritional status, and wellbeing were therefore carried out in 47 consecutive patients (28 males, 19 females; mean age 8.4 years) undergoing bone marrow transplant. 31 diarrhoeal episodes (median duration 9.5 days) occurred in 27 patients at a median of 10 days after transplantation. Ninety one per cent of episodes were associated with protein losing enteropathy. Protein losing enteropathy was more severe in graft-versus-host disease (GVHD) comparing with other causes. It led to a substantial fall in serum albumin and there was a negative correlation between faecal alpha 1-antitrypsin concentrations and serum albumin. Transient pancreatic insufficiency developed in 18 patients, and pancreatitis in one. Intestinal permeability was normal in 12 patients who had no diarrhoea during the conditioning treatments. Diarrhoeal patients had a significantly greater decrease in nutritional status and wellbeing than patients without diarrhoea. Gastrointestinal injury following bone marrow transplantation is thus complex. Severe protein losing enteropathy in this context suggests the presence of GVHD.}, }
@article {pmid8797641, year = {1996}, author = {Wexner, SD and Gonzalez-Padron, A and Rius, J and Teoh, TA and Cheong, DM and Nogueras, JJ and Billotti, VL and Weiss, EG and Moon, HK}, title = {Stimulated gracilis neosphincter operation. Initial experience, pitfalls, and complications.}, journal = {Diseases of the colon and rectum}, volume = {39}, number = {9}, pages = {957-964}, doi = {10.1007/BF02054681}, pmid = {8797641}, issn = {0012-3706}, mesh = {Adult ; Aged ; *Electric Stimulation ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Postoperative Complications ; Prospective Studies ; *Prostheses and Implants ; Treatment Outcome ; }, abstract = {PURPOSE: The stimulated gracilis neosphincter is accepted as a viable option in select patients with fecal incontinence. The aim of this study was to review the initial problems and complications.<br><br>METHODS: A prospective analysis of all patients who underwent this procedure was undertaken. Stage I consisted of the distal vascular delay of the muscle and creation of a temporary stoma. Stage II was the transposition of the muscle and implantation of the stimulator and electrodes. Low frequency electrical stimulation was applied to the muscle for 12 weeks, after which Stage III (stoma closure) was undertaken.<br><br>RESULTS: From March 1993 to December 1995, 17 patients (9 females and 8 males) with a mean age of 42.2 (range, 19-72) years underwent the procedure. One patient died from pancreatitis and another from small-bowel adenocarcinoma, three and six months after the procedure, respectively. Two patients (one with Crohn's disease) required permanent stomas. One additional patient required a permanent stoma because of lead fibrosis. Other complications noted during ascent of the learning curve included seroma of the thigh incision, excoriation of the skin above the stimulator, fecal impaction, anal fissure, parastomal hernia, rotation of the stimulator, premature battery discharge, fracture of the lead, perineal skin irritation, perineal sepsis, rupture of the tendon, tendon erosion, muscle fatigue during programming sessions, and electrode displacement from the nerve or fibrosis around the nerve. However, ultimately after rectification of these problems, 13 of the 15 eligible patients had stoma reversal. Manometric results showed an average basal pressure of 43 mmHg and an average maximum squeeze pressure that increased from 36 mmHg before surgery to 145 mmHg by stimulation (P < 0.01). Based on objective functional questionnaires, 9 of 15 (60 percent) evaluable patients reported improvement in continence, social interactions, and quality of life. Three of these nine patients require daily use of enemas.<br><br>CONCLUSION: Although the stimulated gracilis operation is a feasible procedure for selected patients with severe incontinence, the learning curve is steep. Although the ultimate outcome in a selected group of patients can be very gratifying, major technical modifications are required before use beyond a research protocol setting. Furthermore, patients must have the psychological strength, emotional commitment, and financial resources that may be necessary for multiple revisional surgeries or ultimate device failure.}, }
@article {pmid8764718, year = {1996}, author = {Guelinckx, PJ and Sinsel, NK and Gruwez, JA}, title = {Anal sphincter reconstruction with the gluteus maximus muscle: anatomic and physiologic considerations concerning conventional and dynamic gluteoplasty.}, journal = {Plastic and reconstructive surgery}, volume = {98}, number = {2}, pages = {293-302; discussion 303-4}, doi = {10.1097/00006534-199608000-00013}, pmid = {8764718}, issn = {0032-1052}, mesh = {Adult ; Aged ; Anal Canal/physiopathology/*surgery ; Child ; Electric Stimulation Therapy ; Electrodes, Implanted ; Fecal Incontinence/physiopathology/*surgery ; Female ; Humans ; Male ; Manometry ; Middle Aged ; Muscle Contraction/physiology ; Muscle, Skeletal/*transplantation ; Postoperative Complications/epidemiology ; Pressure ; }, abstract = {Myoplasties have acquired an important place in anal sphincter repair. The use of the gluteus maximus muscle for sphincterplasty was reported initially in 1902. However, in 1952, the gracilis sphincterplasty became more popular because of the accessibility of this muscle. Unfortunately, continence rates, especially after graciloplasty, remained unpredictable because of inability to maintain muscle contraction despite training programs. Training should induce a shift in muscle fiber type distribution toward a more fatigue-resistant composition, with predominance of type I fibers. In order to obtain a more pronounced adaptation in the contractile, histochemical, and metabolic properties of muscle fibers, postoperative intermittent long-term stimulation of the graciloplasty was performed. As these results and the results of dynamic cardiomyoplasty with an implantable myostimulator proved to be successful, implantable pulse generators were used after graciloplasty. Subsequently, continence rates after graciloplasties improved significantly. These data encouraged us to perform dynamic gluteoplasties for anal sphincter repair. This paper presents the results in 7 patients treated by conventional and 4 patients treated by dynamic gluteoplasty. Advantages and disadvantages of gluteoplasty were compared with those of graciloplasty. The neurovascular pedicle of the gluteoplasty underwent less traction after transposition compared with the graciloplasty based on cadaver studies. Gluteus muscle transfer far exceeded the amount of muscle tissue of a normal anal sphincter despite muscle atrophy after transposition. This guaranteed a contractile muscle cuff around the anal canal in contrast to the tendinous sling after graciloplasty. Because of the excellent vascularization of the muscle, microperforations of the rectal mucosa caused by submucosal dissection were sealed, and implantation of electrodes and a pulse generator in one surgical intervention was well tolerated. The myoplasty induced a double curvation of the anal canal in contrast to the graciloplasty, which enhanced the natural anorectal angle. Patient evaluation revealed continence for stool in 9 of the 11 patients; 7 of the 11 patients also were continent for liquids, among them all of the patients who had undergone dynamic gluteoplasties. Mean basal pressure after dynamic gluteoplasty was 49 mmHg, which is lower than the reported mean basal pressure (62 mmHg) during stimulation after dynamic graciloplasty. Squeeze pressure after gluteoplasty, with or without stimulation, proved to be similar to or higher than that obtained in dynamic graciloplasty. Comparing our results of conventional gluteoplasty with the results of graciloplasty prior to stimulation, higher pressures were obtained by the gluteoplasty, especially in squeeze pressures. In the last 5 patients intraoperative pressure measurements were used to restore the optimal resting length of the muscle after transposition. An intraluminal pressure of at least 40 mmHg during rest and 80 to 120 mmHg during stimulation should be obtained to guarantee a future continent sphincter.}, }
@article {pmid8756853, year = {1996}, author = {Geerdes, BP and Konsten, J and Baeten, CG}, title = {Constipation after dynamic graciloplasty.}, journal = {Diseases of the colon and rectum}, volume = {39}, number = {8}, pages = {943}, doi = {10.1007/BF02053996}, pmid = {8756853}, issn = {0012-3706}, mesh = {Anal Canal/surgery ; Constipation/*etiology ; *Electric Stimulation Therapy ; Fecal Incontinence/*surgery ; Humans ; Muscle, Skeletal/*transplantation ; Patient Selection ; Postoperative Complications/*etiology ; }, }
@article {pmid8756848, year = {1996}, author = {Geerdes, BP and Heineman, E and Konsten, J and Soeters, PB and Baeten, CG}, title = {Dynamic graciloplasty. Complications and management.}, journal = {Diseases of the colon and rectum}, volume = {39}, number = {8}, pages = {912-917}, doi = {10.1007/BF02053991}, pmid = {8756848}, issn = {0012-3706}, mesh = {Adult ; Anal Canal/surgery ; Case-Control Studies ; *Electric Stimulation Therapy ; Fecal Incontinence/etiology/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Muscle Contraction/physiology ; Muscle, Skeletal/*transplantation ; Postoperative Complications/*epidemiology/therapy ; Time Factors ; Treatment Failure ; }, abstract = {PURPOSE: Patients with intractable fecal incontinence, in whom all other treatment failed, can be treated by dynamic graciloplasty. Good results have been reported, but this technique involves specific problems. All problems that occurred over an eight-year period are presented, and management is discussed.<br><br>METHODS: Dynamic graciloplasty was performed in 67 patients with a mean follow-up of 2.7 years. All patients were monitored by physical examination, anal manometry, defecography, and electromyography at fixed intervals. All complications were noted and treated. Continence was defined as being continent to solid and liquid stools.<br><br>RESULTS: The technique was successful in 52 patients (78 percent), whereas failures occurred in 15 patients (22 percent). Complications resulted from technical problems, problems with infection, and problems attributable to an abnormal physiology of the muscle or an anorectal functional imbalance. In total, 53 complications were identified in 36 patients. Most technical problems, concerning the transposition and stimulation of the gracilis muscle, could be treated. Failures were attributable to a bad contraction of the distal part of the muscle (n = 4) and perforation of the anal canal during stimulation (n = 1). In eight patients, infection of the stimulator and leads required explantation. Three patients did not regain continence after reimplantation. Apart from moderate constipation, physiologic complications were very hard to treat and resulted in failures in five patients because of overflow incontinence, soiling, a nondistending rectum, strong peristalsis, and strong constipation. In two patients, the technique failed despite a well-contracting graciloplasty; no clear reason for the failure was found.<br><br>CONCLUSION: Complications associated with the technique of dynamic graciloplasty such as loss of contraction, infection, bad contraction in the distal part of the muscle, and constipation can often be prevented or treated. Difficulties related to an impaired sensation and/or motility, attributable to a congenital cause or degeneration, are impossible to treat, and this signifies that a good selection of patients is essential to prevent disappointment.}, }
@article {pmid8819219, year = {1996}, author = {Hove, H and Tvede, M and Mortensen, PB}, title = {Antibiotic-associated diarrhoea, Clostridium difficile, and short-chain fatty acids.}, journal = {Scandinavian journal of gastroenterology}, volume = {31}, number = {7}, pages = {688-693}, doi = {10.3109/00365529609009151}, pmid = {8819219}, issn = {0036-5521}, mesh = {Adult ; Anti-Bacterial Agents/administration &amp; dosage/*adverse effects ; Cefuroxime/administration &amp; dosage/adverse effects ; Cephalosporins/administration &amp; dosage/adverse effects ; Clostridioides difficile/*isolation &amp; purification ; Colon/metabolism/microbiology ; Diarrhea/*chemically induced/metabolism/microbiology ; Fatty Acids, Volatile/*biosynthesis ; Female ; Humans ; Liver Transplantation ; Longitudinal Studies ; Male ; Middle Aged ; Nystatin/administration &amp; dosage/adverse effects ; Tobramycin/administration &amp; dosage/adverse effects ; }, abstract = {BACKGROUND: It has been hypothesized that Clostridium difficile and decreased colonic production of short-chain fatty acids (SCFAs) cause the development of antibiotic-associated diarrhoea. We therefore wanted to investigate the effects of an intensive and uniform antibiotic therapy on faecal SCFAs concentrations. C. difficile, and extent of diarrhoea.<br><br>METHODS: Fifteen liver-transplanted patients who received oral bowel flora suppression therapy (6.3 g cefuroxime, 0.6 g tobramycin, and 0.5 g nystatin three times daily) were studied for 12 days before and 12 days after discontinuation of therapy.<br><br>RESULTS: Thirteen of the 15 patients (87%) developed diarrhoea. Colonic fermentation was negligible in all patients, judged by very low levels of faecal SCFAs (< 10 mmol/l). Diarrhoea lessened as suppression therapy proceeded despite continuous low levels of SCFAs. Initial stool frequency of 4.1 +/- 0.6 and viscosity of 2.5 +/- 0.2 per day (on a scale of 1-3; mean +/- SE) decreased to 2.2 +/- 0.5 (p = 0.0009) and 1.6 +/- 0.2 (p = 0.003) per day, respectively, just before cessation of suppression therapy. Both SCFAs and stool habits normalized within days after discontinuation of antibiotics. Only a few samples from 2 patients were culture-positive for C. difficile during therapy, whereas 9 of the 15 patients (60%) became culture-positive (6 cytotoxin-positive) after cessation of suppression therapy at a time when none had diarrhoea.<br><br>CONCLUSIONS: Intensive treatment with antibiotics directed against the colonic flora resulted in diarrhoea in the vast majority of patients, but the diarrhoea was self-limiting despite continual antibiotic treatment and very low faecal concentrations of SCFAs. C. difficile was not associated with antibiotic-associated diarrhoea but was a common finding after treatment with antibiotics was stopped at the time when diarrhoea had ceased.}, }
@article {pmid8765564, year = {1996}, author = {Givel, JC and Vuilleumier, H and Constanda, MT}, title = {[Dynamic graciloplasty, an effective approach to anal incontinence].}, journal = {Revue medicale de la Suisse romande}, volume = {116}, number = {7}, pages = {521-524}, pmid = {8765564}, issn = {0035-3655}, mesh = {Anal Canal/*surgery ; Electric Stimulation ; Fecal Incontinence/*surgery ; Humans ; Muscle Contraction ; Muscle, Skeletal/innervation/*transplantation ; }, }
@article {pmid8661582, year = {1996}, author = {Marano, I and Grassi, R and Donnianni, T and Gargano, V and Fanucci, A and Romano, G and Pellecchia, L and Rotondano, G}, title = {CT and anal endosonography in the evaluation of electrically stimulated neoanal sphincter: a preliminary report.}, journal = {Abdominal imaging}, volume = {21}, number = {4}, pages = {353-356}, doi = {10.1007/s002619900080}, pmid = {8661582}, issn = {0942-8925}, mesh = {Adult ; Anal Canal/*diagnostic imaging/surgery ; Catheterization/instrumentation ; Defecation ; *Electric Stimulation Therapy ; Fecal Incontinence/*surgery ; Humans ; Male ; Manometry ; Muscle Fibers, Slow-Twitch/physiology ; Muscle Spindles/physiology ; Muscle, Skeletal/diagnostic imaging/innervation/*transplantation ; Pressure ; *Tomography, X-Ray Computed ; Transducers, Pressure ; Ultrasonography ; }, abstract = {We report a preliminary experience concerning the postoperative assessment of three patients who underwent gracilis neosphincter operation for severe fecal incontinence and were studied by computed tomography and anal endosonography soon after gracilis transposition and later after 6-8 weeks of neuromuscular training. Morphologic assessment was correlated with physiologic testing (manometry). Continence was satisfactorily improved in all patients. Both imaging techniques demonstrated the anatomy of the transposed muscle. Computed tomography also assessed lead placement onto the gracilis nerve root and the completeness of muscle transposition around the anal canal. Anal endosonography provided a more accurate assessment of the relation between the neosphincter and residual external sphincter.}, }
@article {pmid8799704, year = {1996}, author = {Camilleri, M}, title = {Gastrointestinal problems in diabetes.}, journal = {Endocrinology and metabolism clinics of North America}, volume = {25}, number = {2}, pages = {361-378}, doi = {10.1016/s0889-8529(05)70328-5}, pmid = {8799704}, issn = {0889-8529}, mesh = {Cholelithiasis/etiology ; Constipation/etiology/therapy ; *Diabetes Complications ; Diabetes Mellitus/physiopathology ; Diarrhea/etiology/therapy ; Esophageal Motility Disorders/etiology ; Gastrointestinal Diseases/diagnosis/*etiology/physiopathology/therapy ; Gastrointestinal Motility ; Gastroparesis/drug therapy/etiology ; Heartburn/etiology ; Humans ; Intestinal Absorption ; Mucous Membrane/physiopathology ; Nausea/etiology ; Vomiting/etiology ; }, abstract = {Gastrointestinal symptoms are often encountered in patients with diabetes mellitus. Symptoms may arise in any region of the alimentary tract; common symptoms are heartburn, nausea, vomiting, diarrhea, constipation, fecal incontinence, and abdominal pain. This article reviews practical approaches to the identification of the pathophysiologic mechanisms involved in diabetic enteropathies and their complications and briefly outlines strategies to treat these symptoms. Particular emphasis is placed on applied physiologic tests and the choice of pharmacotherapy (e.g., cisapride, erythromycin, or octeotide). The current role of pancreatic transplantations also is briefly reviewed.}, }
@article {pmid8783700, year = {1996}, author = {Arnow, PM and Carandang, GC and Zabner, R and Irwin, ME}, title = {Randomized controlled trial of selective bowel decontamination for prevention of infections following liver transplantation.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {22}, number = {6}, pages = {997-1003}, doi = {10.1093/clinids/22.6.997}, pmid = {8783700}, issn = {1058-4838}, mesh = {Ampicillin/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Antibiotic Prophylaxis/*methods ; Bacterial Infections/*prevention &amp; control ; Cefotaxime/therapeutic use ; Colistin/therapeutic use ; Drug Administration Schedule ; Evaluation Studies as Topic ; Feces/microbiology ; Female ; Gentamicins/therapeutic use ; Humans ; Intestines/*microbiology ; Liver Transplantation/adverse effects ; Male ; Mycoses/*prevention &amp; control ; Nystatin/therapeutic use ; Risk Factors ; Treatment Outcome ; }, abstract = {Nonabsorbable antibiotics for selective bowel decontamination (SBD) sometimes are administered to liver transplant patients to prevent postoperative infections, but the efficacy of SBD is not known. Accordingly, we prospectively studied 69 patients randomly assigned to receive conventional prophylaxis with systemic antibiotics (control patients) or conventional prophylaxis plus oral nonabsorbable antibiotics for SBD (SBD patients). Overall rates of bacterial and/or yeast infections were nearly equal among control patients (42%) and SBD patients (39%). However, the infection rate at SBD key sites (abdomen, bloodstream, surgical wound, and lungs) was lower among patients who received the SBD regimen > or = 3 days before transplantation (23%) than among control patients (36%). Administration of the SBD regimen was complicated by gastrointestinal intolerance and noncompliance but not by increased stool colonization with antibiotic-resistant gram-negative bacilli. Practical problems associated with administering an SBD regimen to patients awaiting cadaver liver transplants limit the regimen's usefulness, but we found a trend toward reduced key site infection when the regimen was given > or = 3 days before transplantation.}, }
@article {pmid8842833, year = {1996}, author = {Clerici, C and Setchell, KD and O'Connell, N and Gentili, G and Rusticali, G and Aversa, F and Balo', S and Modesto, R and Morselli-Labate, AM and Martelli, M and Morelli, A}, title = {Effect of ursodeoxycholic acid on hypertransaminasaemia and bile acid composition in patients undergoing bone marrow transplantation--a double-blind randomized control study.}, journal = {The Italian journal of gastroenterology}, volume = {28}, number = {4}, pages = {191-198}, pmid = {8842833}, issn = {0392-0623}, mesh = {Administration, Oral ; Adult ; Alanine Transaminase/*blood ; Alkaline Phosphatase/blood ; Aspartate Aminotransferases/*blood ; Bile Acids and Salts/*metabolism ; *Bone Marrow Transplantation/adverse effects ; Double-Blind Method ; Feces/chemistry ; Female ; Humans ; Liver Diseases/prevention &amp; control ; Lymphocyte Depletion ; Male ; Ursodeoxycholic Acid/*administration &amp; dosage ; }, abstract = {A double-blind randomized placebo controlled trial of ursodeoxycholic acid was performed in 31 patients undergoing T-cell depleted allogeneic or autologous bone marrow transplantation to determine the effectiveness of this hydrophilic bile acid in improving the increase in serum liver enzymes that generally accompanies this procedure. Neither group showed any significant difference in magnitude of the increases in serum transaminases and gamma-glutamyltranspeptidase following the conditioning regimen that included chemotherapy and total body irradiation. In the 6 months after transplantation, serum enzymes decreased in both groups, but were consistently higher in the placebo treated patients, indicating that ursodeoxycholic enhances normalization of liver. Faecal bile acid showed that following chemotherapy and irradiation in which intestinal bacteria are ablated, secondary bile acid formation was practically abolished and faeces contained mainly cholic and chenodeoxycholic acids. During bile acid treatment, ursodeoxycholic acid accounted for 31.3 +/- 10.9% of faecal bile acids compared with 4.0 +/- 2.1% in the basal period. Serum and urinary ursodeoxycholic acid concentrations (mean +/- SD, 13.3 +/- 6.9 mumol/L and 2.65 +/- 0.84 mumol/L, respectively) were significantly higher in patients receiving bile acid than in thos on placebo (mean +/- SD, 0.15 +/- 0.12 mumol/L and 0.29 +/- 0.35 mumol/L, respectively) thus confirming compliance.}, }
@article {pmid8777878, year = {1996}, author = {Buchmann, P and De Lorenzi, D and Müller, A}, title = {[Reinterventions in secondary incontinence].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {67}, number = {5}, pages = {491-497}, pmid = {8777878}, issn = {0009-4722}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Fecal Incontinence/diagnostic imaging/etiology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/transplantation ; Postoperative Complications/diagnostic imaging/etiology/surgery ; Reoperation ; Surgical Flaps/methods ; Suture Techniques ; Treatment Outcome ; Ultrasonography ; }, abstract = {Overlapping sphincter reconstruction for fecal incontinence due to perineal tears, trauma or iatrogenic injuries is the therapy of choice. If this technique fails repeatedly or more than half of the sphincter is destroyed, a gracilis muscle plasty is indicated. Incontinence caused by an ectropion must be treated by a skin flap procedure (Ferguson or VY-plasty). These techniques are described in detail. Results of 54 overlapping procedures carried out in 47 patients (30 females, 17 males, age 15-84, median 47 years) during the last 3.5 years are presented. The most frequent cause of incontinence was fistulectomy followed by perineal tears. Thirty-day success rate with excellent or good results (difficulty in controlling flatus) was 82%, decreasing to 70% at the end of follow-up. Complications were rare (7/54) and did not influence outcome except for wound healing by second intention, which resulted in a high failure rate. Superior results were achieved when the reason for incontinence was a perineal tear (81%, compared with fistulectomy (64%). In conclusion, overlapping sphincter reconstruction results in a high success rate, especially when fecal incontinence was caused by a perineal tear.}, }
@article {pmid8732903, year = {1996}, author = {Ramos, AG and Mitchell, SE and Fair, JH and Colombani, PM and Schwarz, KB}, title = {Severe gastrointestinal bleeding following liver transplantation in young children.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {22}, number = {4}, pages = {389-394}, doi = {10.1097/00005176-199605000-00009}, pmid = {8732903}, issn = {0277-2116}, mesh = {Age Factors ; Biliary Atresia/surgery ; Child ; Child, Preschool ; Female ; Gastrointestinal Hemorrhage/*etiology ; Hepatic Artery ; Humans ; Immunosuppression Therapy ; Infant ; Liver Transplantation/*adverse effects ; Male ; Melena/etiology ; Portal Vein ; Risk Factors ; Thrombosis/etiology ; }, }
@article {pmid8600516, year = {1996}, author = {Burns, JW and Siadat-Pajouh, M and Krishnaney, AA and Greenberg, HB}, title = {Protective effect of rotavirus VP6-specific IgA monoclonal antibodies that lack neutralizing activity.}, journal = {Science (New York, N.Y.)}, volume = {272}, number = {5258}, pages = {104-107}, doi = {10.1126/science.272.5258.104}, pmid = {8600516}, issn = {0036-8075}, support = {DK38707/DK/NIDDK NIH HHS/United States ; R37AI21362/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/administration &amp; dosage/*immunology/metabolism ; Antibodies, Viral/administration &amp; dosage/*immunology/metabolism ; *Antigens, Viral ; Capsid/*immunology ; *Capsid Proteins ; Feces/chemistry/virology ; Hybridomas ; Ileum/immunology/virology ; Immunization, Passive ; Immunoglobulin A, Secretory/administration &amp; dosage/*immunology/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Neutralization Tests ; Rotavirus/*immunology/physiology ; Rotavirus Infections/*immunology/prevention &amp; control/virology ; Virus Replication ; Virus Shedding ; }, abstract = {Rotaviruses are the leading cause of severe gastroenteritis and dehydrating diarrhea in young children and animals worldwide. A murine model and "backpack tumor" transplantation were used to determine the protective effect of antibodies against VP4(an outer capsid viral protein) and VP6(a major inner capsid viral protein). Only two non-neutralizing immunoglobulin A (IgA) antibodies to VP6 were capable of preventing primary and resolving chronic murine rotavirus infections. These antibodies were not active, however, when presented directly to the luminal side of the intestinal tract. These findings support the hypothesis that in vivo intracellular viral inactivation by secretory IgA during transcytosis is a mechanism of host defense against rotavirus infection.}, }
@article {pmid8724169, year = {1996}, author = {Grandjean, P and Acker, M and Madoff, R and Williams, NS and Woloszko, J and Kantor, C}, title = {Dynamic myoplasty: surgical transfer and stimulation of skeletal muscle for functional substitution or enhancement.}, journal = {Journal of rehabilitation research and development}, volume = {33}, number = {2}, pages = {133-144}, pmid = {8724169}, issn = {0748-7711}, mesh = {*Cardiomyoplasty/instrumentation/methods ; *Electric Stimulation Therapy ; Equipment Design ; Fecal Incontinence/*surgery ; Heart Diseases/physiopathology/*surgery ; Humans ; Muscle, Skeletal/*transplantation ; Prognosis ; Urinary Incontinence/*surgery ; }, abstract = {Dynamic myoplasty combines muscle transfer with electrical stimulation to provide contractile function that augments or replaces impaired organ function. Dynamic cardiomyoplasty was the first clinical application in which a skeletal muscle, latissimus dorsi, was transferred and stimulated to provide cardiac assistance, a function different from its original one. The problem of early muscle fatigue that was encountered in the initial implementation of the method was solved by training the muscle with electrical stimulation and thus changing its fiber composition. With intramuscular electrodes, the conditioned latissimus dorsi is stimulated in synchrony with the heart muscle. Safeguards are built into the two-channel implanted stimulator to avoid excessively high pulse rates. Clinicians report that 80% of patients with moderate to severe heart failure prior to operation showed a clinical improvement of 1.6 New York Heart Association classes. Alternative methods of providing cardiac assistance that are also being investigated include wrapping the muscle around the aorta, creating a skeletal muscle ventricle, and using the muscle to power an implantable pump. These latter techniques are still under preclinical investigation. Compared with heart transplant, cardiomyoplasty has the great advantage of not being subject to tissue rejection. The second principal application of dynamic myoplasty is treatment of fecal incontinence through creation of an electrically stimulated skeletal muscle neosphincter (ESMNS). The gracilis muscle of the leg is mobilized, wrapped around the anal canal, and conditioned with electrical stimulation to become more fatigue resistant. To achieve continence, the muscle is continuously stimulated except when the patient wishes to defecate. Overall success rates in achieving continence are 60-65%. Both cardiomyoplasty and the ESMNS technique, and their associated devices, are being refined through ongoing clinical trials.}, }
@article {pmid8663910, year = {1996}, author = {Aboagye, EO and Lewis, AD and Graham, MA and Tracy, M and Kelson, AB and Ryan, KJ and Workman, P}, title = {The pharmacokinetics, bioavailability and biodistribution in mice of a rationally designed 2-nitroimidazole hypoxia probe SR-4554.}, journal = {Anti-cancer drug design}, volume = {11}, number = {3}, pages = {231-242}, pmid = {8663910}, issn = {0266-9536}, mesh = {Animals ; Biological Availability ; Brain/metabolism ; *Cell Hypoxia ; Female ; Liver/metabolism ; Mammary Neoplasms, Experimental/*metabolism ; Mice ; Mice, Inbred BALB C ; *Molecular Probes ; Neoplasm Transplantation ; Nitroimidazoles/*pharmacokinetics/urine ; Tissue Distribution ; }, abstract = {N-(2-Hydroxy-3,3,3-trifluoropropyl)-2-(2-nitro-1-imidazolyl) acetamide (SR-4554) is a fluorinated 2-nitroimidazole which has been rationally designed as a non-invasive probe for tumor hypoxia. The key selection criteria for this molecule were low central nervous system penetration and toxicity, high metabolic stability other than nitroreduction, good tumor uptake and high sensitivity for detection by magnetic resonance spectroscopy. As part of the pre-clinical development strategy, pharmacokinetic, bioavailability and biodistribution studies were performed in mice. Pharmacokinetic studies in mice demonstrated that SR-4554 was rapidly absorbed into plasma following i.p. administration and eliminated with a half-life of 42 min, similar to other 2-nitroimidazoles. By comparing the areas under the concentration-time curve (AUC), the tumor exposure towards SR-4554 was on average 84% of the value obtained for the plasma exposure. SR-4554 penetrated tumor tissue extremely well but, in contrast to misonidazole and certain other fluorinated analogues, its distribution into brain tissue was poor (AUCbrain/AUCplasma = 0.07), suggesting potentially lower toxicity in spite of its higher lipophilicity (P = 0.43 versus 0.63, respectively). The bioavailability of SR-4554 from i.p. and p.o. routes was 100 and 96% respectively. In non-tumor-bearing mice, SR-4554 was excreted mainly as unchanged drug. The percentage of the injected i.p. dose of SR-4554 excreted unchanged in the urine over 24 h was 68 +/- 8%. Neither SR-4554 nor its metabolites were detected in mouse feces. We propose that these favorable pharmacokinetic properties of SR-4554 are due to the hydrophilic character and hydrogen-bonding capability of the amide and hydroxyl functions in the compound.}, }
@article {pmid8620785, year = {1996}, author = {Cavina, E}, title = {Outcome of restorative perineal graciloplasty with simultaneous excision of the anus and rectum for cancer. A ten-year experience with 81 patients.}, journal = {Diseases of the colon and rectum}, volume = {39}, number = {2}, pages = {182-190}, doi = {10.1007/BF02068073}, pmid = {8620785}, issn = {0012-3706}, mesh = {Adenocarcinoma/surgery ; Adult ; Aged ; Aged, 80 and over ; Anus Neoplasms/pathology/*surgery/therapy ; Biofeedback, Psychology ; Carcinoma, Squamous Cell/surgery ; Disease-Free Survival ; Electric Stimulation Therapy ; Fecal Incontinence/etiology/*prevention &amp; control ; Female ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Perineum/innervation/*surgery ; Postoperative Complications ; Rectal Neoplasms/pathology/*surgery/therapy ; Survival Analysis ; Thigh/surgery ; Treatment Outcome ; }, abstract = {PURPOSE: To review the complications, survival, and long-term functional outcome of patients with anorectal cancer who had restorative perineal graciloplasty (RPG) simultaneously with abdominoperineal resection (APR).<br><br>METHODS: Between 1985 and 1994, 81 patients underwent APR plus RPG. Gracilis muscles were then conditioned by electrostimulation, either intermittently or chronically. Thirtyseven surviving patients were followed for a mean of 78.6 months and were analyzed for long-term functional outcome of RPG.<br><br>RESULTS: Postoperative complications occurred in 30 patients (37 percent). Crude five-year survival rate was 58 percent, and five-year estimated cumulative probability of survival was 65 percent. There was no statistically significant difference for probability of survival and for probability of disease-free interval between uncomplicated and complicated patients. Fecal continence was obtained in 90 percent of patients.<br><br>CONCLUSION: RPG does not reduce the effectiveness of APR in the cure of cancer. Postoperative complications, though frequent, were not serious and resolved without sequelae. There was no statistically significant impact on the probability of survival and of disease-free interval by graciloplasty. Continence was achieved by most patients (90 percent) who underwent RPG simultaneously with APR.}, }
@article {pmid10021696, year = {1996}, author = {Violi, V and Roncoroni, L and Boselli, AS and De Cesare, C and Livrini, M and Peracchia, A}, title = {Continent perineal colostomy by electrostimulated graciloplasty in abdominoperineal resection. A preliminary report.}, journal = {Acta bio-medica de L'Ateneo parmense : organo della Societa di medicina e scienze naturali di Parma}, volume = {67}, number = {3-4}, pages = {131-142}, pmid = {10021696}, mesh = {Abdomen/*surgery ; Aged ; Colostomy/*methods ; *Electric Stimulation Therapy/methods ; Fecal Incontinence/*prevention &amp; control ; Female ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/physiology/*transplantation ; Perineum/*surgery ; Postoperative Complications/*prevention &amp; control ; Rectal Neoplasms/surgery ; }, abstract = {Despite the tendency toward sphincter-saving surgical procedures, a small proportion of rectal cancers must still be treated by abdominoperineal resection (APR). The physical, psychological and social consequences of a permanent abdominal stoma are a challenge to perform a continent perineal colostomy. Most of the attempts originate from experiences with gracilis muscle transposition in the treatment of fecal incontinence, in particular Pickrell's operation. Functional results are however conditioned by the fact that the transposed muscle takes up a different function and its natural evolution, if not adequately stimulated, consists of atrophy and fibrosis. The most important series of graciloplasty in APR is reported by Cavina and coworkers (75 cases from 1985 to 1993), who at first obtained good functional results by external electromyostimulation (EMS) and biofeedback, then registered a further improvement using internal, continuous low-frequency EMS by implantable pulse generators (IPG). The surgical technique involves, after APR: bilateral dissection of the gracilis up to the proximal neurovascular pedicle and detachment of the distal tendon; mobilization of the muscles, through the subcutaneous tissue, into the perineum, where the colonic stump is drawn out; positioning the right gracilis behind the colonic stump, as a puborectalis sling, and the left gracilis around it, in a sort of "alpha" configuration; suturing the colonic stump to the perineal skin; optionally, temporary diverting loop colostomy. The operation is completed by the insertion of two electrodes near the nerve, for external or internal EMS (in the last case: implantation of IPG). The external EMS may be carried out by current cardiac temporary electrodes, drawn up through the skin of the iliac area. It is aimed at preserving the trophism and the contractility of the muscle and enabling the patient to learn a new function of continence (actually, it is a "pseudocontinence"), thanks to a program of intermittent stimulation and biofeedback. Electrodes and other devices are not expensive. The internal EMS requires specific electrodes, connected to an IPG, implanted in a subcutaneous abdominal pocket. The continuous stimulation gives rise to a tonic activity of the gracilis, resulting in higher resting anal pressure and "true" continence. The IPG is programmed under telemetry control, step by step until the most suitable EMS parameters are reached. A magnet allows the patient to turn the IPG "off" of "on", according to the necessity to void the bowel. A complete set of 1 IPG and 2 electrodes costs about $10,000. Cavina reports good continence in 71% of the cases treated by external EMS and 100% of the patients with IPG. Our first graciloplasty in APR was performed in April 1994. Since then we have carried out 6 operations. Because of its high cost, we decided that, at least at a first phase, the IPG should be implanted, from the 7th month on, only in disease-free patients, when functional results suggested a possible clinical improvement. Until today, 3 patients have had the abdominal stoma closed and can be evaluated from a functional viewpoint. We recorded 1 "excellent" and 2 "fair" results. In the two patients with a "fair" result we implanted a pulse generator about a month after the closure of the abdominal colostomy. A good manometric and clinical improvement was registered. The patient with "excellent" functional result had a recurrence one month after the closure of the stoma. Though limited, our experience is absolutely favourable as to graciloplasty, but an evaluation from us whether external or internal EMS is better, is too early at the moment. In absolute functional terms, the internal, continuous EMS is preferable, but problems of cost and oncologic prognosis restrict the use of IPG.}, }
@article {pmid8966911, year = {1996}, author = {Komissarov, IA}, title = {[The surgical treatment of fecal incontinence in children].}, journal = {Vestnik khirurgii imeni I. I. Grekova}, volume = {155}, number = {2}, pages = {60-62}, pmid = {8966911}, issn = {0042-4625}, mesh = {Anal Canal/surgery ; Child ; Fecal Incontinence/diagnosis/etiology/*surgery ; Female ; Humans ; Male ; Methods ; Muscle Denervation ; Muscle, Skeletal/transplantation ; Polyethylene Terephthalates ; Surgical Flaps/methods ; Surgical Mesh ; }, abstract = {Based on his experience with treatment of 112 children the author considers that severe and various disturbances of the rectum abturative apparatus function arising from surgical interventions in the anorectal area require the differentiated approach to choice of the method of surgical correction of the incontinence. The transplantation of the denervated muscle, transplantation of the vascular-nervous thoraco-dorsal flap, a lavsan band were used to make a pubo-rectal loop, plasty of the outer and inner sphincters being performed mainly with local tissues.}, }
@article {pmid8951515, year = {1996}, author = {Altomare, DF and Rinaldi, M and Pannarale, O and Martinelli, E and Palasciano, N and Memeo, V}, title = {Vaginal repair of rectocele after dynamic graciloplasty for fecal incontinence due to imperforate anus.}, journal = {International journal of colorectal disease}, volume = {11}, number = {5}, pages = {243-245}, doi = {10.1007/s003840050054}, pmid = {8951515}, issn = {0179-1958}, mesh = {Adult ; Anal Canal/*surgery ; Anus, Imperforate/complications/physiopathology/*surgery ; Defecation ; Electric Stimulation Therapy ; Fecal Incontinence/complications/etiology/physiopathology/*surgery ; Female ; Humans ; Methods ; Muscle, Skeletal/*transplantation ; Postoperative Complications/etiology/physiopathology/*surgery ; Rectal Prolapse/etiology/physiopathology/*surgery ; Vagina/*surgery ; }, abstract = {A 35-years-old woman developed obstructed defecation due to a large (6 cm) non-emptying rectocele one year after successful electrostimulated gracilis neosphincter operation for correction of fecal incontinence after surgery for imperforate anus. Surgical correction of the rectocele was performed by a trans-vaginal approach due to the poor elasticity of the neoanus and avoidance of possible damage to the neosphincter. After physiological investigations, including defecography, the patient had a resection of the posterior vaginal mucosal wall, a double layer plication of the muscular wall with non-absorbable suture and a longitudinal mucosal suture. The postoperative course was uneventful. Defecography, performed 3 and 6 months later, showed a marked reduction of the rectocele (2 cm) which corresponded to clinical improvement. Occurrence of disabling rectocele can be considered a possible long term complication after successful electrostimulated neosphincter procedure in patients at risk for developing a rectocele; a successful repair can be obtained using trans-vaginal approach without the risk of neosphincter damage. Transvaginal repair of rectocele in similar clinical situations may be recommended.}, }
@article {pmid8919335, year = {1996}, author = {Sielezneff, I and Bauer, S and Bulgare, JC and Sarles, JC}, title = {Gracilis muscle transposition in the treatment of faecal incontinence.}, journal = {International journal of colorectal disease}, volume = {11}, number = {1}, pages = {15-18}, pmid = {8919335}, issn = {0179-1958}, mesh = {Adult ; Aged ; Anal Canal/physiopathology ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Middle Aged ; Muscle, Skeletal/*transplantation ; Pressure ; *Thigh ; }, abstract = {Between 1965 and 1994 eight selected patients with faecal incontinence for solid stool (Grade 4) were operated on by the original procedure described by Pickrell (1952), combined with biofeedback training postoperatively. No postoperative complication occurred. All patients were improved by this procedure. Five had normal continence and there were 3 incontinence for flatus. Anal manometry showed an increase in postoperative squeeze pressure (p < 0.05). Long term results (48.5 months) remained the same in five cases. One patient became incontinent following an anal dilatation at 108 months, and two required excision of mucosal ectropion at 7 and 78 months with restoration of continence. One patient died of unrelated disease at 31 months.}, }
@article {pmid8893154, year = {1996}, author = {Hida, M and Aiba, Y and Sawamura, S and Suzuki, N and Satoh, T and Koga, Y}, title = {Inhibition of the accumulation of uremic toxins in the blood and their precursors in the feces after oral administration of Lebenin, a lactic acid bacteria preparation, to uremic patients undergoing hemodialysis.}, journal = {Nephron}, volume = {74}, number = {2}, pages = {349-355}, doi = {10.1159/000189334}, pmid = {8893154}, issn = {1660-8151}, mesh = {Administration, Oral ; Adult ; Bacteria, Aerobic/isolation &amp; purification ; Bacteria, Anaerobic/isolation &amp; purification ; *Bifidobacterium ; Capsules ; Cresols/*blood ; *Enterococcus faecalis ; Feces/microbiology ; Female ; Humans ; Indican/*blood ; *Lactobacillus acidophilus ; Male ; Middle Aged ; Phenol ; Phenols/*blood ; *Renal Dialysis ; Uremia/*blood/*therapy ; }, abstract = {The plasma levels of phenol, p-cresol, and indican are markedly increased in uremic patients, and cannot be efficiently reduced by hemodialysis. Such uremic toxins, which are produced in the intestine as bacterial putrefactive metabolites, accumulate to a great degree in the feces of hemodialysis patients. Oral administration of Lebenin, a preparation consisting of antibiotic-resistant lactic acid bacteria, reduced the levels of fecal putrefactive metabolites to levels comparable with those of healthy subjects. Moreover, the plasma level of indican also significantly decreased in these Lebenin-treated patients. An analysis of the fecal microflora revealed that a disturbed composition of the microflora characterized by an overgrowth of aerobic bacteria is restored to normal by oral administration of Lebenin in hemodialysis patients. These results thus demonstrate that oral administration of lactic acid bacteria in uremic patients is effective in reducing the levels of uremic toxins, especially that of indican, in the blood by inhibiting bacterial production by means of correcting the intestinal microflora.}, }
@article {pmid8788266, year = {1996}, author = {Kiyozaki, H and Kobayashi, E and Toyama, N and Miyata, M}, title = {Segmental small bowel transplantation in the rat: comparison of lipid absorption between jejunal and ileal grafts.}, journal = {JPEN. Journal of parenteral and enteral nutrition}, volume = {20}, number = {1}, pages = {67-70}, doi = {10.1177/014860719602000167}, pmid = {8788266}, issn = {0148-6071}, mesh = {Animals ; Bile/chemistry/metabolism ; Bile Acids and Salts/analysis ; Body Weight ; Feces/chemistry ; Ileum/*transplantation ; *Intestinal Absorption ; Jejunum/*transplantation ; Lipase/blood ; Lipids/analysis ; Lymphography ; Male ; Oleic Acid ; Oleic Acids/pharmacology ; Rats ; Rats, Inbred Lew ; }, abstract = {BACKGROUND: From the immunological point of view, it is very important to evaluate the efficacy of segmental small bowel transplantation and to determine which part of the intestine, jejunum, or ileum should be used. In the present study, we investigated the absorptive function of the transplanted jejunum and ileum in the rat.<br><br>METHODS: Syngeneic segmental small bowel transplantation (jejunal or ileal grafting) was performed. After surgery, body weight and fecal fat excretions were measured. In addition, bile acid concentration in bile juice was measured, and the response of both serum lipase and bile flow rate after oleic acid stimulation was evaluated. Recanalization of the lymphatic vessels was investigated by lymphangiography.<br><br>RESULTS: There was no significant difference in body weight change between normal controls, jejunum-transplanted rats, and ileum-transplanted rats. In short gut rats, however, body weight was significantly impaired. Fecal fat excretion in short gut rats was the highest in the four groups, and it was significantly lower in ileal grafts than in jejunal grafts. Ileum-transplanted rats also showed a significantly higher bile acid concentration in bile juice than jejunum-transplanted rats. After oleic acid stimulation, serum lipase responded better in ileal transplants than in jejunal transplants, but the bile flow rate did not show significant change in either group. Recanalization of the lymphatic vessels was established on the 28th postoperative day.<br><br>CONCLUSIONS: These results clearly show that ileal transplantation is more conducive to lipid absorption than jejunal transplantation.}, }
@article {pmid8785623, year = {1996}, author = {Romano, G and Rotondano, G and Esposito, P and Pellecchia, L and Novi, A}, title = {External anal sphincter defects: correlation between pre-operative anal endosonography and intraoperative findings.}, journal = {The British journal of radiology}, volume = {69}, number = {817}, pages = {6-9}, doi = {10.1259/0007-1285-69-817-6}, pmid = {8785623}, issn = {0007-1285}, mesh = {Adult ; Aged ; Anal Canal/*diagnostic imaging/*injuries/surgery ; Fecal Incontinence/diagnostic imaging/etiology/surgery ; Female ; Humans ; Intraoperative Period ; Male ; Middle Aged ; Muscle, Skeletal/transplantation ; Preoperative Care ; Sensitivity and Specificity ; Ultrasonography ; }, abstract = {In order to correlate operative findings with external anal sphincter (EAS) defects identified on anal endosonography (AES), 30 faecally incontinent patients undergoing overlapping sphincteroplasty or total pelvic floor repair were investigated by AES before and after surgery. Endosonic findings were correlated with the appearance of EAS at operation. 21 out of 22 defects seen at surgery had been pre-operatively detected by AES (one false negative). Post-operatively the sphincteroplasty was clearly evident on AES. In three cases of failure it showed an extensive hypoechoic area and these patients underwent dynamic graciloplasty. Endosonography is the method of choice for pre-operative imaging of EAS, having an established role in identifying sphincter defects and correlating well with intraoperative findings. Post-operatively, it has the potential to identify breakdown of the previous repair, allowing prompt surgical intervention. Endosonography is helpful in planning the best type of operation following sphincter injury and is useful in auditing the results of surgery.}, }
@article {pmid8753964, year = {1996}, author = {Komissarov, IA and Ul'rikh, EV}, title = {[The possibilities for the surgical treatment of neurogenic fecal incontinence in children].}, journal = {Vestnik khirurgii imeni I. I. Grekova}, volume = {}, number = {1}, pages = {63-65}, pmid = {8753964}, issn = {0042-4625}, mesh = {Anal Canal/surgery ; Child ; Child, Preschool ; Combined Modality Therapy ; Fecal Incontinence/diagnosis/etiology/*surgery ; Follow-Up Studies ; Humans ; Muscle Denervation ; Muscles/transplantation ; }, abstract = {Treatment of anal incontinence in children with a pathology of the distal portion of the spine is a serious problem. We observed 36 children aged from 3 to 6 years with the 3rd degree of fecal incontinence. Twenty patients had spina bifida, 12 had meningocele, 4 children had the following symptoms: disturbed formation of the arches, sacrum agenesia, deformity of the distal portion of the spine. The conservative treatment was effective but in children without concomitant neurological disorders (motor disorders of the lower extremities, disturbance of the perineum sensitivity). Great increase of the ano-rectal angle and decreased pressure in the anal canal were found in 12 patients with meningocele and in 4 children with severe defects of the vertebral column. They were subjected to operation of free transplantation of the preliminarily denervated muscle by the Hakelius method. Good effects were obtained in 10 cases of 12 operations.}, }
@article {pmid8740554, year = {1996}, author = {Christensen, CM and Barnes, EH and Nansen, P and Grøndahl-Nielsen, C}, title = {Growth and fecundity of Oesophagostomum dentatum in high-level infections and after transplantation into naive pigs.}, journal = {Parasitology research}, volume = {82}, number = {4}, pages = {364-368}, doi = {10.1007/s004360050127}, pmid = {8740554}, issn = {0932-0113}, mesh = {Animals ; Feces/parasitology ; Female ; Fertility ; Male ; Oesophagostomiasis/physiopathology/*veterinary ; Oesophagostomum/growth &amp; development/isolation &amp; purification/*physiology ; Parasite Egg Count ; Swine ; *Swine Diseases ; }, abstract = {This experiment was designed to examine the growth, proportion of stages, and fecundity of an Oesophagostomum dentatum population by transplantation of a known small number of worms from a high-density population into helminth-naive recipient pigs. Approximately 1,500 4-week-old worms [69% fourth-stage larvae (L4), 31% adult worms] were transplanted into each of 5 recipient pigs (group B), and these pigs, along with a group of 5 high-level-infection control pigs (group C), were killed at 4 weeks after transplantation to determine and compare the worm burdens. By 2 weeks after transplantation and throughout the experiment, fecal egg counts of group B exceeded those of group C and the fecundity of the worms was higher, though not statistically significantly so, in the transplanted worms. In the recipient pigs, all worms (approx. 70% establishment) had developed to the adult stage and were significantly longer than worms recovered from the group C pigs.}, }
@article {pmid8583123, year = {1995}, author = {Bjørn, H and Roepstorff, A and Grøndahl, C and Eriksen, L and Bjerregaard, J and Nansen, P}, title = {Experimental transfer of adult Oesophagostomum dentatum from donor to helminth naive recipient pigs: a methodological study.}, journal = {Journal of helminthology}, volume = {69}, number = {4}, pages = {279-283}, doi = {10.1017/s0022149x0001484x}, pmid = {8583123}, issn = {0022-149X}, mesh = {Animals ; Cecum/parasitology ; Digestive System/*parasitology ; Digestive System Surgical Procedures ; Feces/parasitology ; Female ; Male ; Oesophagostomiasis/*veterinary ; Oesophagostomum/*growth &amp; development ; Parasite Egg Count ; Stomach/parasitology ; Swine ; Swine Diseases/*parasitology ; }, abstract = {This study was carried out to compare potential methods of transplanting adult Oesophagostomum dentatum from experimentally infected donor pigs to helminth naive recipient pigs. The following methods were each tested in five pigs: A. Transfer of worms by stomach tube to the gastric ventricle of pigs per os pretreated with 0.5 mg/kg cisapride to increase gastrointestinal peristalsis; B. Transfer by stomach tube to the gastric ventricle of pigs per os pre-treated with cisapride (0.5 mg/kg) and omeprazol 20 mg which blocks hydrochloric acid secretion; C. Surgical transfer of worms to caecum of pigs. Worms for transplantation to pigs were obtained after slaughter of experimentally infected donor pigs and following isolation from the contents of the large intestine, using an agar gel migration technique. A mean of 1054 nematodes were transferred into each recipient pig within 2 hours. Procedures A and B resulted in establishment rates corresponding to only 0.5% and 7.6% of the transferred worms. In contrast, surgical transfer allowed 74.2% of the transplanted worms to be established. In all groups the transplanted worms migrated to the normal predilection site, i.e. the middle part of the large intestine. More female than male worms established in all groups. It was concluded from this study that surgical transfer was the most reliable of the methods tested for experimental establishment of adult O. dentatum in helminth naive pigs.}, }
@article {pmid8548229, year = {1995}, author = {Kumar, D and Hutchinson, R and Grant, E}, title = {Bilateral gracilis neosphincter construction for treatment of faecal incontinence.}, journal = {The British journal of surgery}, volume = {82}, number = {12}, pages = {1645-1647}, doi = {10.1002/bjs.1800821219}, pmid = {8548229}, issn = {0007-1323}, mesh = {Adult ; Aged ; Colostomy ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Pressure ; Treatment Outcome ; }, abstract = {Neosphincter formation with gracilis muscle is used for faecal incontinence refractory to conservative measures and after failed sphincter repair. In this study both gracilis muscles were used to create a neosphincter to determine whether this provides superior physiological and clinical results. Ten patients of median age 39 (range 18-73) years were treated. The mean resting and squeeze pressures before operation were 16 (range 0-40) and 44 (range 0-68) cmH2O respectively. The operation was covered by a defunctioning loop left iliac fossa colostomy. Nine of the ten patients have had the stoma closed and are fully continent after a mean follow-up of 24 (range 6-40) months. One patient who had an ileoanal pouch and bilateral graciloplasty has urgency of defaecation. None of the patients has to wear a pad or is taking constipating agents. All nine patients have satisfactory evacuation on isotope defaecography and are continent to artificial stool. After operation the mean resting and squeeze pressures were 78 (range 70-112) and 121 (range 90-188) cmH2O respectively. Bilateral graciloplasty provides satisfactory results for grade 4 faecal incontinence refractory to other operative and non-operative measures, and may be an alternative to stimulated dynamic graciloplasty.}, }
@article {pmid7497849, year = {1995}, author = {Korsgen, S and Keighley, MR}, title = {Stimulated gracilis neosphincter--not as good as previously thought. Report of four cases.}, journal = {Diseases of the colon and rectum}, volume = {38}, number = {12}, pages = {1331-1333}, doi = {10.1007/BF02049162}, pmid = {7497849}, issn = {0012-3706}, mesh = {Administration, Rectal ; Adult ; Anal Canal/physiopathology/*surgery ; Bisacodyl/administration &amp; dosage/therapeutic use ; Cathartics/administration &amp; dosage/therapeutic use ; Colectomy/rehabilitation ; Colostomy ; Constipation/surgery ; Defecation ; Electric Stimulation ; Fecal Incontinence/physiopathology/*surgery ; Female ; Humans ; Middle Aged ; Muscle, Skeletal/*transplantation ; Rectum/physiopathology ; Suppositories ; Treatment Failure ; Treatment Outcome ; }, abstract = {PURPOSE: We report the outcome of four patients who had stimulated gracilis neosphincter for fecal incontinence to highlight functional problems, particularly in patients with impaired rectal evacuation.<br><br>METHODS: The gracilis neosphincter operation consisted of a three-stage procedure in four patients with intractable incontinence, three of whom had had a pelvic floor repair.<br><br>RESULTS: Despite successful muscle transposition and nerve stimulation, only one of four patients has a functioning neosphincter. One patient could not tolerate stimulation, and two were unable to evacuate the rectum. All three now have stomas, and even the functioning neosphincter patient requires regular bisacodyl (Dulcolax; CIBA Consumer Pharmaceuticals, Woodbridge, NJ) suppositories to achieve evacuation.<br><br>CONCLUSION: The neosphincter is a successful sphincter but has no role for patients who cannot evacuate from the rectum.}, }
@article {pmid8668835, year = {1995}, author = {Lanura, PN and Matsubara, L and Amato Neto, V and Okumura, M and Bocchi, EA}, title = {[The characteristics of Trypanosoma cruzi strains isolated from patients who have undergone a heart transplant].}, journal = {Revista da Sociedade Brasileira de Medicina Tropical}, volume = {28}, number = {4}, pages = {351-356}, doi = {10.1590/s0037-86821995000400008}, pmid = {8668835}, issn = {0037-8682}, mesh = {Adolescent ; Adult ; Animals ; Chagas Cardiomyopathy/parasitology/pathology/surgery ; Disease Models, Animal ; Feces/parasitology ; Female ; *Heart Transplantation ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Parasitemia/parasitology/pathology ; Postoperative Period ; Time Factors ; Trypanosoma cruzi/*isolation &amp; purification/pathogenicity ; }, abstract = {Three strains of Trypanosoma cruzi were isolated from Chagas' disease patients transplanted for heart failure, after cardiac transplantation, and were studied in an experimental model of Chagas' disease, in mice, with evaluation of parasitic load, mortality and extension of inflammatory infiltrates in the heart. These parameters were compared with the standard strain Y. The strains had differences in the studied parameters, but there was no clear relationship between those and post-transplant evolution of the patients. Probably the clinical response is multifactorial and derives only in part from biological characteristics of the infecting T. cruzi strain, as measured in our model.}, }
@article {pmid7483681, year = {1995}, author = {Han, SJ and Park, HJ and Kim, CB and Hwang, EH}, title = {Long-term follow-up of gracilis muscle transposition in children.}, journal = {Yonsei medical journal}, volume = {36}, number = {4}, pages = {372-377}, doi = {10.3349/ymj.1995.36.4.372}, pmid = {7483681}, issn = {0513-5796}, mesh = {Adolescent ; Adult ; Anal Canal/physiopathology ; Child ; Child, Preschool ; Colostomy ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Infant ; Longitudinal Studies ; Male ; Manometry ; Muscles/*transplantation ; Postoperative Period ; Reoperation ; Thigh ; Treatment Outcome ; }, abstract = {Sixteen children of uncontrollable fecal incontinence have been treated with Pickrell's gracilis muscle transposition since 1983: 12 had an imperforate anuses with multiple corrective operative procedures and 4 had traumatic destructions of anal sphincters. We report a series of 11 cases whom we followed-up over a period of 0.8 to 10.5 years (mean; 5.6 years). Seven patients were evaluated by anorectal manometry. All patients except one who had left hemipelvectomy and permanent colostomy showed nearly normal continence during the follow-up period. There was no evidence of fibrosis in the transposed muscles and the tensions of the transposed muscles were well maintained. The voluntary contractions of the transposed muscles were well maintained and efficient in all cases. The general manometric parameters did not correlate well with the functional results; however, there was a strong correlation in the S/R ratio (maximum squeeze pressure/resting pressure) with the functional results. We believe that the good functional outcome of this procedure need not only the meticulous surgical technique but also the personal motivation and the compliance with physiotherapy. In conclusion, although the gracilis muscle transposition never results in normal continence, acceptable continence can be achieved in the selected patients.}, }
@article {pmid7648103, year = {1995}, author = {Christiansen, J and Hansen, CR and Rasmussen, O}, title = {Bilateral gluteus maximus transposition for anal incontinence.}, journal = {The British journal of surgery}, volume = {82}, number = {7}, pages = {903-905}, doi = {10.1002/bjs.1800820715}, pmid = {7648103}, issn = {0007-1323}, mesh = {Adult ; Anal Canal/physiopathology/*surgery ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/*transplantation ; Postoperative Care ; Preoperative Care ; Pressure ; Surgical Wound Infection/etiology ; }, abstract = {Seven patients (five women and two men) with anal incontinence in whom previous surgery had failed, were treated by bilateral gluteus maximus transposition. All patients were incontinent to solid stool. Previous surgery was postanal repair in four women and secondary overlapping suture for obstetric tear in one. The two men were treated in childhood for anal atresia. No covering stoma was used. Wound infection occurred in three patients, requiring surgical drainage in two. After follow-up of more than 1 year three patients experienced improved continence but in four continence was unchanged. Anorectal physiology studies showed moderately increased resting and squeeze pressures in patients who were improved by the operation, but none could retain more than 200 ml of viscous fluid instilled into the rectum. No change in rectal sensitivity or volume tolerance was found. This preliminary series does not indicate that better results are obtained by gluteus maximus transposition than by unstimulated graciloplasty.}, }
@article {pmid7548456, year = {1995}, author = {Beukeveld, GJ and Bijleveld, CM and Kuipers, F and Kreeftenberg, HG and Huizenga, JR and te Velde, K and Wolthers, BG}, title = {Evaluation and clinical application of the Enterotest for the determination of human biliary porphyrin composition.}, journal = {European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies}, volume = {33}, number = {7}, pages = {453-462}, pmid = {7548456}, issn = {0939-4974}, mesh = {Adult ; Aged ; Bile/*chemistry/metabolism ; Bile Acids and Salts/*analysis ; Cholecystokinin/pharmacology ; Chromatography, High Pressure Liquid/methods ; Duodenum/microbiology/physiology/physiopathology ; Feasibility Studies ; Feces/chemistry ; Female ; Gallbladder/drug effects/physiology ; Humans ; Intestinal Mucosa/chemistry/microbiology ; Liver Transplantation ; Longitudinal Studies ; Male ; Middle Aged ; Porphyria, Erythropoietic/*physiopathology/surgery ; Porphyrias, Hepatic/diagnosis/*physiopathology ; Porphyrins/*analysis/urine ; Reagent Kits, Diagnostic ; Reference Values ; }, abstract = {The Enterotest string test is an easy and non-invasive method for sampling duodenal fluid, which has been successfully used for the analysis of duodenal microflora, as well as biliary bile acid and lipid composition. The method was evaluated for determination of porphyrins in duodenal bile in normal subjects and subjects with porphyria, following cholecystokinin induced gall bladder contraction; it is known that analysis of biliary porphyrins is more discriminatory for the diagnosis of asymptomatic porphyria than their analysis in faeces or urine. Moreover, serial analysis of bile from patients with erythropoietic protoporphyria may help in establishing their ability to secrete protoporphyrin in bile and to assess effects of treatment. The binding of various porphyrins to Enterotest strings was investigated by incubating pieces of the string in different human bile samples with low to very high porphyrin concentrations, followed by HPLC analysis of porphyrins both in the native bile and in extracts obtained from the strings. No differences between porphyrin composition in native bile and extracts were observed. Duodenal fluid obtained by means of the Enterotest from volunteers not receiving cholecystokinin showed large variations in porphyrin patterns not resembling those of native bile. Mesoporphyrin, a secondary porphyrin derived from protoporphyrin by bacteria, was often detectable. These data indicate that the duodenal content without cholecystokinin injection does not reflect biliary porphyrin composition. The presence of mesoporphyrin in the whole intestinal tract, but not in serum and bile, suggests that there is no enterohepatic circulation of secondary porphyrins. There was close agreement between the porphyrin ratios found with the standard duodenal intubation technique and the Enterotest, performed simultaneously in one healthy volunteer after induction of gall bladder contraction by cholecystokinin. From these experiments, it was concluded that fluid adsorbed to the Enterotest string after gall-bladder contraction can be used to determine biliary porphyrin composition. Since duodenal bile is diluted gall bladder bile, variable porphyrin concentrations were found when applying the Enterotest in combination with cholecystokinin in the same subject on successive days. However, porphyrin ratios, such as the protoporphyrin to coproporphyrin I ratio, were relatively constant. In subjects with symptomatic variegate porphyria, the Enterotest showed highly aberrant porphyrin patterns, with increased protoporphyrin to coproporphyrin I ratios and, in addition, the presence of some unknown porphyrins. A deviating biliary protoporphyrin/coproporphyrin I ratio in one patient appeared to be a useful diagnostic index for the presence of latent variegate porphyria (or variegate porphyria in remission).(ABSTRACT TRUNCATED AT 400 WORDS)}, }
@article {pmid7753138, year = {1995}, author = {Baeten, CG and Geerdes, BP and Adang, EM and Heineman, E and Konsten, J and Engel, GL and Kester, AD and Spaans, F and Soeters, PB}, title = {Anal dynamic graciloplasty in the treatment of intractable fecal incontinence.}, journal = {The New England journal of medicine}, volume = {332}, number = {24}, pages = {1600-1605}, doi = {10.1056/NEJM199506153322403}, pmid = {7753138}, issn = {0028-4793}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/physiopathology/*surgery ; Electrodes, Implanted ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Male ; Manometry ; Middle Aged ; Muscle, Skeletal/*transplantation ; Prospective Studies ; Quality of Life ; }, abstract = {BACKGROUND: In patients with intractable fecal incontinence, conventional treatment is not always successful. Dynamic graciloplasty (transposition of the gracilis muscle to the anus with the implantation of stimulating electrodes) was developed to provide such patients with functional neosphincters. We evaluated the clinical results of this new surgical approach and the effects on quality of life.<br><br>METHODS: We treated 52 patients with dynamic graciloplasty. The clinical results of treatment were evaluated in an interview, by anal manometry, and by enema testing. The degree of continence was scored. To assess quality of life, four questionnaires were administered (parts 1 and 2 of the Nottingham Health Profile, the State-Trait Anxiety Inventory, and the Self-rating Depression scale).<br><br>RESULTS: Among the 52 patients, 38 (73 percent) were continent after a median follow-up of 2.1 years. At 52 weeks the patients' condition had improved with respect to the median frequency of defecation (from five to two times per 24 hours, P < 0.001), the median time defecation could be postponed (from 9 seconds to 19 minutes, P = 0.012), and the median time an enema could be retained (from 0 to 180 seconds, P = 0.005). Patients in whom the technique was successful became less anxious than those in whom it failed (P = 0.002) and improved with regard to effectiveness in their occupations, ability to perform tasks around the home, personal relationships, sexual function, and social life (P = 0.01). They also became less isolated socially (P = 0.05).<br><br>CONCLUSIONS: Dynamic graciloplasty is a safe and reliable technique in patients with severe incontinence and may result in a better quality of life.}, }
@article {pmid7774467, year = {1995}, author = {Shafik, A}, title = {Perianal injection of autologous fat for treatment of sphincteric incontinence.}, journal = {Diseases of the colon and rectum}, volume = {38}, number = {6}, pages = {583-587}, doi = {10.1007/BF02054115}, pmid = {7774467}, issn = {0012-3706}, mesh = {Adipose Tissue/*transplantation ; Adult ; *Anal Canal ; Fecal Incontinence/*therapy ; Female ; Humans ; Injections ; Male ; Middle Aged ; Transplantation, Autologous/adverse effects ; }, abstract = {PURPOSE: The aim of this study was to evaluate the results of treatment of partial fecal incontinence with perianal injection of autologous fat.<br><br>METHODS: The study comprised 14 patients with partial fecal incontinence (9 women and 5 men). Ages ranged from 38 to 62 years. Fifty to 60 ml of fat were harvested from the abdominal wall and injected submucosally into the rectal neck at 3 and 9 o'clock positions. Mean follow-up was 18.6 months.<br><br>RESULTS: All patients were continent during the first two to three postinjection months. At the sixth month, patients were divided into three scores. Score 1 (complete continence) comprised three patients who are now continent for 9, 11, and 14 months postinjection, with normalization of their rectal neck pressure. Seven patients with Score 2 were incontinent to flatus and were reinjected; they are now continent (Score 1) for a mean of 13.8 months and have normal rectal neck pressure. Four patients had Score 3 (no improvement), of whom two became continent after the second injection and two after the third. They are now continent (Score 1) 6 to 16 months postinjection. Factors that contributed to failure comprised injection of unwashed fat or wrong positioning of the needle. There was no fat migration or embolism.<br><br>CONCLUSION: Perianal fat injection is effective in treatment of partial fecal incontinence. The technique is simple, easy, cost-effective, and performed on an outpatient basis.}, }
@article {pmid7666309, year = {1995}, author = {Erdogan, E and Rode, H and Hickman, R and Cywes, S}, title = {Transposition of the antropylorus for anal incontinence--an experimental model in the pig.}, journal = {Journal of pediatric surgery}, volume = {30}, number = {6}, pages = {795-800}, doi = {10.1016/0022-3468(95)90750-5}, pmid = {7666309}, issn = {0022-3468}, mesh = {Animals ; Defecation ; Fecal Incontinence/physiopathology/*surgery ; Male ; Pressure ; Pylorus/*transplantation ; Swine ; Treatment Outcome ; }, abstract = {An experimental model in the pig rendered incontinent of feces was developed to assess the sphincteric activity of the transposed antropylorus. In the control group, normal defecation was studied clinically, radiologically, and manometrically. Nineteen 7- to 10-week-old pigs were rendered incontinent by resection of 20 cm of colon and rectum to below the dentate line. The antropylorus was prepared on its own blood supply and transposed to the anus, initially with a colostomy, which was closed 15 to 21 days later. Clinically these pigs passed semisolid stool in a piecemeal fashion. Contrast defecography showed hold-up at the pylorus, reflux of contrast into the colon, with pyloric contraction independent of antral stimulation. Manometry showed pyloric contraction with rise in antral pressure and independence. The authors conclude that transposition of an antropyloric segment to the anus provides a sphincter-like mechanism and could have application in fecal incontinence.}, }
@article {pmid7587942, year = {1995}, author = {Mangold, JB and Rodriguez, LC and Wang, YK}, title = {Metabolism of cyclosporin G in the mouse, rat, and dog.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {23}, number = {6}, pages = {615-621}, pmid = {7587942}, issn = {0090-9556}, mesh = {Amino Acid Sequence ; Animals ; Chromatography ; Cyclosporine/blood/*metabolism/urine ; Dogs ; Feces/chemistry ; Immunosuppressive Agents/blood/*metabolism/urine ; Mass Spectrometry ; Mice ; Mice, Inbred Strains ; Molecular Sequence Data ; Rats ; Rats, Sprague-Dawley ; Species Specificity ; }, abstract = {Cyclosporin G (CsG; Sandoz compound OG 37-325) is a cyclic undecapeptide with potent, immunosuppressive activity and is currently in clinical testing for prevention of transplanted solid organ rejection. Although structurally similar to cyclosporin A (CsA), results in animals suggest that CsG has a reduced potential for nephrotoxicity when compared with CsA, while retaining equivalent therapeutic efficacy. In the present study, the major metabolic pathways of CsG in the mouse, rat, and dog were investigated using radiolabeled drug substance to determine if interspecies differences in metabolism exist. The results indicated that the major metabolic pathways in these animal species are similar to those previously reported for CsA, including oxidative modifications at amino acids 1, 4, and 9, and concomitant cyclization of amino acid 1 in two of these metabolites. Moreover, the seven major CsG metabolites (designated GM19, GM1c9, GM4N9, GM1, GM9, GM1c, and GM4N) observed in animal excreta and/or blood were identical to those identified in humans. The major circulating metabolite in blood was GM9 (9-hydroxylated CsG) in all species. In addition, numerous unidentified minor metabolites were observed. Renal excretion was a minor elimination pathway, with the majority of drug-related material excreted via the fecal route. In conclusion, CsG was found to proceed through the same metabolic pathways in three animal species and humans, and that species differences in metabolism were primarily because of differences in the relative importance of the pathways observed.}, }
@article {pmid7736876, year = {1995}, author = {Versluis, PJ and Konsten, J and Geerdes, B and Baeten, CG and Oei, KT}, title = {Defecographic evaluation of dynamic graciloplasty for fecal incontinence.}, journal = {Diseases of the colon and rectum}, volume = {38}, number = {5}, pages = {468-473}, doi = {10.1007/BF02148845}, pmid = {7736876}, issn = {0012-3706}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/pathology/physiopathology ; Case-Control Studies ; *Defecation ; *Electric Stimulation Therapy ; Evaluation Studies as Topic ; Fecal Incontinence/pathology/physiopathology/*surgery ; Female ; Gastrointestinal Motility ; Humans ; Male ; Manometry ; Middle Aged ; Muscle Contraction ; Muscle, Skeletal/physiology/*transplantation ; Postoperative Complications ; Prospective Studies ; Rectum/pathology/physiopathology ; Treatment Outcome ; }, abstract = {PURPOSE: A prospective defecographic study was performed to evaluate the anorectal physiology of dynamic graciloplasty (gracilis muscle transposition and subsequent implantation of an electric stimulator) for treatment of fecal incontinence.<br><br>METHODS: From November 1986 until May 1993, 38 consecutive patients with incapacitating fecal incontinence were treated with "anal dynamic graciloplasty." Defecography was performed before and after surgical procedures. Defecographic data (anorectal angle, perineal descent, anal canal length, anal canal width, and anal leakage) were correlated with respect to clinical outcome and anal manometry.<br><br>RESULTS: Fecal continence was achieved in 24 patients, which correlated significantly with no leakage of barium contrast during defecography (P < 0.01, Kruskal-Wallis one-way analysis of variance). In addition, minimum anal canal width decreased from 7 mm before surgery to 1 mm after dynamic graciloplasty (P < 0.01, paired Student's t-test).<br><br>CONCLUSION: Defecography is an efficient method to evaluate dynamic graciloplasty for fecal incontinence.}, }
@article {pmid7610750, year = {1995}, author = {Soravia, C and Baldi, A and Kartheuser, A and Mourad, M and Kestens, PJ and Detry, R and Squifflet, JP}, title = {Acute colonic complications after kidney transplantation.}, journal = {Acta chirurgica Belgica}, volume = {95}, number = {3}, pages = {157-161}, pmid = {7610750}, issn = {0001-5458}, mesh = {Abdomen, Acute/etiology ; Adult ; Child ; Colonic Diseases/*etiology/surgery ; Diverticulitis, Colonic/etiology ; Female ; Humans ; Intestinal Perforation/etiology ; *Kidney Transplantation ; Male ; Middle Aged ; Peritonitis/etiology ; Postoperative Complications/*etiology ; }, abstract = {Over a 30-year period (1963-1993), 12 patients out of 2091 renal allograft recipients (0.5%) were identified for an acute colonic complication. They were 7 males and 5 females with a mean age of 43 years. The mean elapsed time from transplantation to symptoms was 55 months. Peritonitis was diagnosed in all cases, requiring an emergency laparotomy in 6 patients (50%); delayed surgery was possible in 4 patients (33%) after failure of conservative treatment. One patient (9%) was operated electively later on while the last patient died before any surgery from sepsis after diffuse bowel ischaemia. Aetiology included complicated diverticulitis in 9 instances (75%), one colon perforation caused by faecal impaction, one cytomegalovirus colitis and one bowel ischaemia. Another patient died postoperatively after colon resection for perforated diverticulitis. The use of cyclosporine since 1985 did not reduce the incidence of colonic complication. In conclusion aggressive medical support and early surgical exploration are mandatory for renal recipients presenting with an acute colonic complication.}, }
@article {pmid7607017, year = {1995}, author = {Köhler, L and Mennigen, R and Troidl, H}, title = {[Dynamic gracilis muscle-plasty--a case report].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {66}, number = {5}, pages = {522-525}, pmid = {7607017}, issn = {0009-4722}, mesh = {Adenoma, Villous/physiopathology/*surgery ; Aged ; Anal Canal/physiopathology/*surgery ; Electric Stimulation Therapy/instrumentation ; Fecal Incontinence/physiopathology/*surgery ; Humans ; Male ; Manometry ; Muscle Tonus/physiology ; Muscle, Skeletal/physiopathology/*transplantation ; Prostheses and Implants ; Rectal Neoplasms/physiopathology/*surgery ; }, abstract = {The feasibility of anal dynamic graciloplasty (transposition of the gracilis muscle and subsequent implantation of a stimulation device) to restore continence, was assessed in a 71 year old patient. Anal dynamic graciloplasty was capable to achieve continence by increasing the sphincter tone from 35 mm Hg without stimulation to 110 mm Hg with stimulation. The clinical results and anal manometry data are described and the pros and cons of the procedure are discussed.}, }
@article {pmid7633783, year = {1995}, author = {Abercrombie, JF and Williams, NS}, title = {Development of an electrically-stimulated skeletal muscle neoanal sphincter.}, journal = {Bailliere's clinical neurology}, volume = {4}, number = {1}, pages = {21-34}, pmid = {7633783}, issn = {0961-0421}, mesh = {Anal Canal/*innervation ; Animals ; Electric Stimulation Therapy/*instrumentation ; Equipment Design ; Equipment Failure ; Fecal Incontinence/*rehabilitation ; Humans ; Microsurgery/methods ; Muscle, Skeletal/*innervation/*transplantation ; Postoperative Complications/rehabilitation ; Rectal Neoplasms/surgery ; }, }
@article {pmid7760228, year = {1995}, author = {Wolvekamp, MC and Heineman, E and Marquet, RL and Meijssen, MA and de Bruin, RW and Molenaar, JC}, title = {Segmental intestinal transplantation can be an adequate therapy for short bowel syndrome in growing dogs.}, journal = {Journal of pediatric surgery}, volume = {30}, number = {3}, pages = {396-401}, doi = {10.1016/0022-3468(95)90040-3}, pmid = {7760228}, issn = {0022-3468}, mesh = {Anastomosis, Roux-en-Y ; Animals ; Cyclosporine/therapeutic use ; Dogs ; Female ; Growth Disorders/etiology ; Histocompatibility Testing ; Ileum/*transplantation ; Intestinal Absorption/physiology ; Jejunum/*transplantation ; Male ; Short Bowel Syndrome/physiopathology/*surgery ; Transplantation, Homologous ; }, abstract = {This study was undertaken to investigate whether two-stage segmental small bowel allotransplantation can maintain growth and development of young dogs (16 weeks, 5 to 6 kg) with surgically created short bowel syndrome (SBS). After near-total small bowel resection (group 1; n = 3), irreversible weight loss was noted. After a sham operation (group 2; n = 3), no growth disturbances were found. Major histocompatibility matched small bowel transplantation (SBT) with cyclosporine A as immunosuppressant, was performed in two stages (group 3; n = 7). During the first stage, one meter of jejunoileum from an adult donor was placed as a Roux loop. Four weeks later, the native small bowel was removed and replaced by the graft. Only one dog survived long-term; the dogs died from infectious complications. The addition of selective decontamination of the digestive tract and early gastrostomy feeding (group 4; n = 10) resulted in long-term survival in 60%. Follow-up at 4 months showed that their growth was about 20% compromised compared with that of the sham-operated animals. Functional analysis showed that electrolytes, urea, and D-xylose were normal, but there was an increase in the lactulose:mannitol ratio, fecal fat excretion, and postheparin diamine oxidase release. These results show that under the conditions described, segmental SBT functions sufficiently to treat SBS but does not maintain normal growth.}, }
@article {pmid7618044, year = {1995}, author = {Shokeir, AA}, title = {Bladder cancer following ileal ureter. Case report.}, journal = {Scandinavian journal of urology and nephrology}, volume = {29}, number = {1}, pages = {113-115}, doi = {10.3109/00365599509180549}, pmid = {7618044}, issn = {0036-5599}, mesh = {Carcinoma, Squamous Cell/*etiology ; Humans ; Ileum/*transplantation ; Male ; Middle Aged ; Postoperative Complications/*etiology ; Ureter/*surgery ; Urinary Bladder Neoplasms/*etiology ; }, abstract = {We report a case of squamous cell carcinoma of the ileovesical junction 12 years following total replacement of the ureter with ileum. The uroenteric junctions, which are not exposed to the fecal stream, may be associated with cancer as in ureterosigmoidostomy. The urine infected with fecal bacterial flora combined with a healing uroenteric suture line may be responsible for the tumorigenesis. Urine cytology should be performed at least yearly beginning 10 years after ileal ureter. If any abnormality was suspected cystoscopy must be performed.}, }
@article {pmid8554298, year = {1995}, author = {Jung, JL and Abouelfadel, Z}, title = {[Simplified urinary diversion in colostomized patients].}, journal = {Annales d'urologie}, volume = {29}, number = {4}, pages = {255-257}, pmid = {8554298}, issn = {0003-4401}, mesh = {Aged ; Aged, 80 and over ; Colon/transplantation ; Colostomy/*methods ; Female ; Follow-Up Studies ; Humans ; Ureter/surgery ; Urinary Diversion/*methods ; Urinary Reservoirs, Continent/methods ; }, abstract = {The authors report 3 cases of urinary diversion in patients with preexisting colostomy and operated by technique of Noble and Davis. The previous colostomy is used for urinary diversion and new colostomy is created for fecal diversion. This method is simple, time-saving and very beneficial for high risk patients. We found it very useful and had gave us satisfactory results.}, }
@article {pmid8554297, year = {1995}, author = {Bruezière, J}, title = {[Uretero-colonic implantation in children. Late results].}, journal = {Annales d'urologie}, volume = {29}, number = {4}, pages = {250-254}, pmid = {8554297}, issn = {0003-4401}, mesh = {Acid-Base Imbalance/etiology ; Adenocarcinoma/etiology ; Anastomosis, Surgical/methods ; Bladder Exstrophy/surgery ; Child ; Colon/*surgery/transplantation ; Colon, Sigmoid/surgery ; Fecal Incontinence/etiology ; Female ; Humans ; Kidney Neoplasms/etiology ; Male ; Pyelonephritis/surgery ; Renal Insufficiency/etiology ; Ureter/surgery ; Ureteral Calculi/etiology ; Ureterostomy/adverse effects/methods ; Urinary Bladder/surgery ; Urinary Diversion/adverse effects/*methods ; Vesico-Ureteral Reflux/surgery ; }, abstract = {An uretereo-colic anastomosis in children is performed in three occasions: 1) The trans-intestinal cutaneous ureterostomy (Bricker) has a low rate of complications concerning ureterocolic anastomosis. Nevertheless, occurrence of pyelonephrites may oblige to perform an anti-reflux procedure. 2) Implantation of ureters in the intestinal segment of an augmentation colocystoplastys in unusual; when necessary, this type of implantation is safe because colon is appropriate for an antireflux procedure. 3) Ureterocolic diversion (Coffey) is quite comfortable for patients. Risks of renal failure and of adenocarcinoma are minimal thanks to an annual control. Concerning exstrophy of bladder, it seems now that risk of infertility is lower for patients with an ureterocolic diversion than those with a genito-urinary reconstruction.}, }
@article {pmid7745639, year = {1995}, author = {Konsten, J and Geerdes, B and Versluis, P and Heineman, E and Baeten, GM}, title = {Dynamic graciloplasty for restoration of continence after traumatic destruction of the rectum and sphincters: report of a case.}, journal = {The Journal of trauma}, volume = {38}, number = {1}, pages = {11-13}, doi = {10.1097/00005373-199501000-00005}, pmid = {7745639}, issn = {0022-5282}, mesh = {Adolescent ; Anal Canal/*injuries ; Electric Stimulation ; Fecal Incontinence/etiology/*surgery ; Female ; Humans ; Muscle, Skeletal/*transplantation ; Rectum/*injuries ; Treatment Outcome ; }, abstract = {A thirteen-year-old girl was run down by a speedboat, which resulted in traumatic destruction of the rectum and anal sphincters. She was treated by using a modified Duhamel procedure for rectal reconstruction and a double gracilis muscle transposition as the sphincter replacement procedure. Eight weeks after the first operation, intramuscular electrodes were implanted in both gracilis muscles and connected with an implanted electrical stimulator. This electrically stimulated gracilis muscle neosphincter restored sphincter function while anorectal sensation was preserved as a result of an intact rectovaginal septum. After closure of the temporary colostomy, the patient has good continence.}, }
@article {pmid7742757, year = {1995}, author = {Liu, KL and Herbrecht, R and Lioure, B and Jaulhac, B and Maloisel, F and Dufour, P and Bergerat, JP and Oberling, F}, title = {Effects of bacterial naso-oropharyngeal colonisation on acute graft-versus-host disease in patients undergoing allogeneic bone marrow transplantation.}, journal = {Bone marrow transplantation}, volume = {15}, number = {1}, pages = {65-69}, pmid = {7742757}, issn = {0268-3369}, mesh = {Acute Disease ; Adolescent ; Adult ; Bacterial Infections/*etiology/prevention &amp; control ; *Bone Marrow Transplantation ; Child ; Child, Preschool ; Feces/microbiology ; Female ; Graft vs Host Disease/*microbiology/therapy ; HLA Antigens ; Humans ; Male ; Middle Aged ; Mycoses/*etiology/prevention &amp; control ; Nasopharynx/*microbiology ; Retrospective Studies ; Survival Rate ; }, abstract = {The efficacy of gastrointestinal decontamination in reducing the incidence of severe bacterial or fungal infections and of moderate to severe acute graft-versus-host disease (GVHD) has been suggested. We report here a retrospective study of 71 patients grafted consecutively in our institution with bone marrow from HLA genotypically identical siblings. Complete decontamination (plastic isolator or laminar airflow room, sterile nursing and oral antimicrobial drugs) was carried out in all patients. Sixty eight patients were evaluable. Only six patients had aerobic Gram negative rods or anaerobic bacteria in their faeces and 44 of 68 (65%) had yeasts in their faeces. Most patients had oropharyngeal and/or nasal colonisation with bacteria (Gram positive cocci: 39 patients (57%); Gram negative rods: 13 patients (19%)) or yeasts (29 patients (43%)). Thirty nine patients (57%) experienced severe grade > or = II acute GVHD (grade II-IV). A significant relation was found between bacterial oropharyngeal or nasal colonisation and GVHD (P < 0.01) but not between gastrointestinal microflora and GVHD, whatever microorganisms were considered (bacteria, yeasts).}, }
@article {pmid7674604, year = {1995}, author = {Komissarov, IA}, title = {[Treatment of anal incompetence in children by free graft of denervated muscle].}, journal = {Khirurgiia}, volume = {}, number = {4}, pages = {28-29}, pmid = {7674604}, issn = {0023-1207}, mesh = {Adolescent ; Age Factors ; Child ; Child, Preschool ; Fecal Incontinence/rehabilitation/*surgery ; Female ; Humans ; Male ; *Surgical Flaps ; }, abstract = {Transplantation of a denervated muscle imitating a levator loop allows pathogenetic correction of anal incompetence. Its results depend on the patient's participation in the rehabilitation process to a lesser extent than the results of plastics of the external sphincter ani by the traditional methods. This is of certain significance in pediatric practice and makes it possible to operate on younger children. This method produces satisfactory results in the so-called hopeless patients suffering from meningocele and concomitant developmental anomalies of the spine. This makes it possible to widen significantly the indications for surgical treatment of children with fecal incontinence.}, }
@article {pmid7640452, year = {1995}, author = {Shatari, T and Teramoto, T and Kitajima, M and Minamitani, H}, title = {Conversion of the rabbit gracilis muscle for transposition as a neoanal sphincter by electrical stimulation.}, journal = {Surgery today}, volume = {25}, number = {3}, pages = {233-236}, pmid = {7640452}, issn = {0941-1291}, mesh = {Anal Canal/*surgery ; Animals ; Electric Stimulation/*methods ; In Vitro Techniques ; Male ; Muscle Contraction/physiology ; Muscles/*physiology/*transplantation ; Rabbits ; }, abstract = {To re-establish anal function in fecally incontinent patients it may be feasible to transpose the gracilis muscle around the anal canal, using electrical stimulation to trigger contraction. However, because the fast-twitching gracilis muscle is incapable of prolonged contraction without fatigue, it is necessary to convert it to a slow-twitching, fatigue-resistant muscle. We demonstrated this conversion by longterm electrical stimulation at low frequencies using a rabbit model. The nerve to the gracilis muscle was continuously stimulated at 2 Hz, 5 Hz, and 10 Hz for 2, 4, or 6 weeks. In the 6-week conditioning group, the percentage of type I fibers, identified by ATPase staining, increased as the conditioning frequency became higher, but the twitch contraction speed reduced with conditioning at a frequency of more than 5 Hz. The fatigue resistance improved by conditioning at 10 Hz, and conversion occurred in 6 weeks. Thus, we concluded that conditioning at 10 Hz for 6 weeks can convert rabbit gracilis muscle to a slow-twitching, fatigue-resistant muscle suitable for use as a neoanal sphincter.}, }
@article {pmid7637682, year = {1995}, author = {Hoppe, JE and Klingebiel, T and Niethammer, D}, title = {Orointestinal yeast colonization of paediatric bone marrow transplant recipients: surveillance by quantitative culture and serology.}, journal = {Mycoses}, volume = {38}, number = {1-2}, pages = {51-57}, doi = {10.1111/j.1439-0507.1995.tb00008.x}, pmid = {7637682}, issn = {0933-7407}, mesh = {Adolescent ; Adult ; Antibodies, Fungal/blood ; *Bone Marrow Transplantation ; Candida/immunology/*isolation &amp; purification ; Child ; Child, Preschool ; Feces/*microbiology ; Female ; Fluconazole/therapeutic use ; Humans ; Infant ; Longitudinal Studies ; Male ; Mouth/*microbiology ; Premedication ; Prospective Studies ; }, abstract = {We quantitatively studied the orointestinal yeast colonization of 15 consecutive paediatric patients who underwent 16 bone marrow transplantations (BMT). Cultures were performed initially, longitudinally weekly during the period of aplasia (in-patient treatment) and, if possible, also during out-patient follow-up. With one exception, all patients received fluconazole as antifungal prophylaxis. Patients remained free of yeasts during the complete observation period only in six out of 16 cases (38%). Non-albicans species of Candida were isolated in six out of 16 cases (38%), mainly C. glabrata (five out of 16; 31%). All of these patients had undergone allogeneic BMT. In one case, there was indirect evidence of systemic invasion by C. glabrata. Even combined prophylaxis with fluconazole and and amphotericin B suspension could not reliably prevent yeast colonization but this combination at present appears to be the optimal regime. Regular concomitant Candida serology (determination of specific antibodies by three methods) proved to be a valuable additional surveillance method.}, }
@article {pmid7616708, year = {1995}, author = {Tat'ianchenko, VK and Ovsiannikov, AV}, title = {[Ways of raising viability of the intestinal obturator made of the gracilis muscle].}, journal = {Khirurgiia}, volume = {}, number = {2}, pages = {49-51}, pmid = {7616708}, issn = {0023-1207}, mesh = {Anal Canal/abnormalities/surgery ; Child ; Fecal Incontinence/rehabilitation/*surgery ; Female ; Follow-Up Studies ; Humans ; Muscle, Skeletal/*transplantation ; Polarography ; Rehabilitation/instrumentation ; Time Factors ; }, abstract = {Polarographic examination was conducted in 10 patients with incompetence of the sphincter ani to study the effect of biological preparation of the gracilis muscle for creation of intestinal obturator apparatus. It was established that in initial 20% reduction of pO2, in response to compression of additional vessels and training of 30 to 60 minutes not only a sufficient arterial flow of blood to the muscle through its main supplying vessel develops but also the previously nonfunctioning network of anastomoses. Stabilization of pO2 is an objective criterion of the preparedness of the muscle for transplantation. The method for preoperative training of the transplant is quite simple and reliable, which allows it to be applied in clinical practice.}, }
@article {pmid7774419, year = {1994}, author = {Chen, YL and Cui, XH and Li, JL}, title = {[A transposition of iliopsoas in replacement of pelvic floor for incontinence of urination and/or defecation in children].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {32}, number = {12}, pages = {724-726}, pmid = {7774419}, issn = {0529-5815}, mesh = {Child ; Child, Preschool ; Fecal Incontinence/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Pelvic Floor/*surgery ; Psoas Muscles/*transplantation ; Urinary Incontinence/*surgery ; }, abstract = {Fourteen patients, the age ranged from 2 to 12 years, with fecal and/or urinary incontinence were treated between 1991 and 1993 using a transposition of iliopsoas in replacement or strengthening of pelvic floor. The results were encouraging. The evaluation of the function of pelvic floor was described. Levator plays an important role in normal mechanism of defecation as well as urination. Several types of incontinence develop while the disfunction of pelvic floor occur and some function of continence could be restored by an operation of transposition of iliopsoas.}, }
@article {pmid7924718, year = {1994}, author = {Faucheron, JL and Hannoun, L and Thome, C and Parc, R}, title = {Is fecal continence improved by nonstimulated gracilis muscle transposition?.}, journal = {Diseases of the colon and rectum}, volume = {37}, number = {10}, pages = {979-983}, doi = {10.1007/BF02049308}, pmid = {7924718}, issn = {0012-3706}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/physiopathology/*surgery ; Child ; Colostomy ; Combined Modality Therapy ; Defecation ; *Electric Stimulation Therapy ; Electrodes, Implanted ; Fecal Incontinence/physiopathology/*therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle Contraction ; Muscles/*transplantation ; Postoperative Complications/etiology/physiopathology/*therapy ; Reoperation ; Time Factors ; }, abstract = {PURPOSE: Gracilis muscle transposition for treatment of fecal incontinence gives variable results. Electric stimulation of transposed muscle recently brought this technique to the surface.<br><br>METHODS: We reviewed patients who had gracilis muscle transposition for fecal incontinence to determine who might benefit from electrostimulation.<br><br>RESULTS: Between 1979 and 1991, 22 patients underwent gracilis muscle transposition. At six months, 18 patients had improved continence, but 12 of the 18 were stable with time, and only 1 was fully continent. Six patients were candidates for electrostimulation; four had a contractile but fatigable transposed muscle, and two had ineffective transposed muscle with a gaping nonfibrotic anus.<br><br>CONCLUSION: Gracilis muscle transposition should be used first for severe incontinent patients, and electrostimulation should be used if there are unsatisfactory results.}, }
@article {pmid7819014, year = {1994}, author = {Gregorio, GV and Mowat, AP}, title = {Viral hepatitis in children with renal disease.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {8}, number = {5}, pages = {610-619}, pmid = {7819014}, issn = {0931-041X}, mesh = {Child ; Hepatitis/*complications/diagnosis/therapy ; Hepatitis B/diagnosis/therapy ; Hepatitis C/diagnosis/therapy ; Hepatitis D/diagnosis/therapy ; Humans ; Kidney Diseases/*complications ; Kidney Transplantation/adverse effects ; Risk Factors ; Transfusion Reaction ; }, abstract = {Specific and sensitive diagnostic tests are now available to identify type A, B, C, D and E hepatitis. Hepatitis A and E which cause only acute, very rarely fulminant, hepatitis are spread largely by the faecal-oral route, having a brief viraemic phase. Hepatitis B, C and D which are transmitted parenterally and via secretions are often associated with chronic viraemia. Patients with chronic renal disease are at particular risk. Impaired immunity due to disease or drugs increases the propensity to develop a chronic carrier state which may progress to cirrhosis and hepatocellular carcinoma. Limited reports indicate that hepatitis C infection may cause cirrhosis more rapidly than hepatitis B. The emergence of mutants to both hepatitis B and C is a cause for concern. Treatment with interferon is of limited efficacy. Screening of blood products for viral markers and prudent handling of potentially infected materials to avoid contamination of damaged skin or mucous membrane are the best strategies to prevent infection. Hepatitis B vaccination of all newborns, young adolescents and those at risk is the most effective means of reducing the carrier frequency.}, }
@article {pmid8076489, year = {1994}, author = {Seccia, M and Menconi, C and Balestri, R and Cavina, E}, title = {Study protocols and functional results in 86 electrostimulated graciloplasties.}, journal = {Diseases of the colon and rectum}, volume = {37}, number = {9}, pages = {897-904}, doi = {10.1007/BF02052595}, pmid = {8076489}, issn = {0012-3706}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma/mortality/physiopathology/*therapy ; Clinical Protocols ; Combined Modality Therapy ; Defecation ; Electric Stimulation Therapy/instrumentation/*methods ; Electrodes, Implanted ; Fecal Incontinence/classification/epidemiology/physiopathology/*therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Middle Aged ; Muscles/*transplantation ; Proctocolectomy, Restorative/*methods ; Rectal Neoplasms/mortality/physiopathology/*therapy ; Reproducibility of Results ; Severity of Illness Index ; Survival Rate ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE: This study analyzes different protocols adopted in 86 electrostimulated graciloplasties performed during the last eight years, comparing functional and manometry results in 63 patients.<br><br>METHODS: Electrostimulated graciloplasties were performed to construct a neosphincter after surgical removal of the anorectum for cancer in 75 patients and to substitute the anal sphincter in 11 fully incontinent patients. An intermittent stimulation protocol, using external devices, was applied in the first 68 patients, while long-term stimulation was carried out with implantable stimulators and intramuscular electrodes in the last 18 patients. Sixty-three patients remaining under study were evaluated by questionnaires, continence scores, and manometry.<br><br>RESULTS: In patients submitted to intermittent stimulation, continence was achieved in 71 percent of 42 "neosphincters" after rectal resection and in 33 percent of 3 incontinent patients. Adopting chronic stimulation, implantable stimulators and intramuscular electrodes, continence reached 100 percent and 83 percent, respectively. Significant differences were also observed in resting and voluntary pressure values between the intermittently and chronically stimulated patients. Incontinent patients showed after chronic stimulation significant increases in mean resting and maximum voluntary pressures: from 13.3 to 60.5 mmHg and from 32 to 103 mmHg, respectively (P < 0.01).<br><br>CONCLUSIONS: This study confirms the efficacy of chronic stimulation and the validity of a bilateral, "one-time" graciloplasty to reconstruct or substitute the anal sphincter.}, }
@article {pmid8062591, year = {1994}, author = {Ziegler, MM}, title = {Meconium ileus.}, journal = {Current problems in surgery}, volume = {31}, number = {9}, pages = {731-777}, doi = {10.1016/0011-3840(94)90040-x}, pmid = {8062591}, issn = {0011-3840}, mesh = {Cystic Fibrosis/complications/genetics ; Diagnosis, Differential ; Humans ; Infant, Newborn ; *Intestinal Obstruction/diagnosis/etiology/surgery/therapy ; *Meconium ; }, abstract = {Meconium ileus is a manifestation of intestinal and pancreatic dysfunction that results in the accumulation of a sticky and inspissated intraluminal meconium, which in most cases results from the autosomal recessive disease cystic fibrosis. Both nonoperative and operative therapies are effective in relieving this small-bowel obstruction; in the past, although less so today, a successful nonoperative treatment was associated with a more favorable outcome. Once the meconium ileus is relieved successfully, and the diagnosis of cystic fibrosis is established, the treatment for the intestinal manifestations of the disease focuses on enzyme replacement to augment patient nutritional status. Simultaneously, the treatment of the life-threatening pulmonary disease focuses on mucous retention and chronic infection in the lungs. Future therapies for patients with cystic fibrosis include lung transplantation, pharmacologic manipulation of the epithelial cell abnormality, and gene transfer therapy into the respiratory epithelium.}, }
@article {pmid7531053, year = {1994}, author = {Munechika, K and Sogame, Y and Kishi, N and Kawabata, Y and Ueda, Y and Yuamanouchi, K and Yokoyama, K}, title = {Tissue distribution of macromolecular conjugate, adriamycin linked to oxidized dextran, in rat and mouse bearing tumor cells.}, journal = {Biological &amp; pharmaceutical bulletin}, volume = {17}, number = {9}, pages = {1193-1198}, doi = {10.1248/bpb.17.1193}, pmid = {7531053}, issn = {0918-6158}, mesh = {Animals ; Carcinoma 256, Walker/metabolism ; Cell Transplantation ; Chromatography, Gel ; Dextrans/pharmacokinetics ; Doxorubicin/*analogs &amp; derivatives/*pharmacokinetics ; Feces/chemistry ; Lung Neoplasms/metabolism ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Rats ; Rats, Wistar ; Tissue Distribution ; }, abstract = {Tissue distribution of the radioactivities after intravenous administration of [14C]adriamycin ([14C]ADM) or [14C]ADM linked to oxidized dextran ([14C]ADM-OXD) in mouse bearing Lewis lung carcinoma (LLC) and rat bearing Walker 256 carcinosarcoma was studied. ADM conjugated with OXD increased plasma half-life and gave high area under the plasma concentration-time curve (AUC). The AUC values were 13.0 and 5.8 times higher than those of the [14C]ADM group in mice and rats, respectively. In the tumor tissues, AUC values of the [14C]ADM-OXD group were also respectively 1.6 and 1.9 times higher than those of the [14C]ADM group. However, the AUC values in the heart of the [14C]ADM-OXD group were about half those of [14C]ADM group in both animals. Thus the distribution of ADM was changed by the conjugation with OXD. The excretion profile of ADM was also changed by the conjugation. During 6 h after administration, [14C]ADM-OXD was mainly excreted into rat urine at 45.2% of the original dose, but in the [14C]ADM group recovery in urinary excretion was 4.2%. Using [14C]ADM-OXD and ADM-[14C]OXD, the respective tissue distribution of ADM and OXD portions in the ADM-OXD was studied in rats bearing Walker 256. The radioactivities of both [14C]ADM-OXD and ADM-[14C]OXD groups increased in tumor and liver within 1 h after administration. In the liver, both radioactivities were retained for 24 h, which suggested that ADM and OXD were retained as conjugated form, however, different behavior was observed between the two groups in tumor tissues.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid7993569, year = {1994}, author = {Price, BA and Cumberland, NS and Ingham Clark, CL and Pockley, AG and Lear, PA and Wood, RF}, title = {Effect of small bowel transplantation, denervation and ischaemia on rat intestinal microflora.}, journal = {Transplant international : official journal of the European Society for Organ Transplantation}, volume = {7}, number = {5}, pages = {334-339}, doi = {10.1007/BF00336708}, pmid = {7993569}, issn = {0934-0874}, mesh = {Animals ; *Autonomic Denervation ; Bacteria, Aerobic/isolation &amp; purification ; Colony Count, Microbial ; Intestinal Mucosa/microbiology ; Intestine, Small/blood supply/microbiology/*transplantation ; Ischemia/*microbiology/physiopathology ; Male ; Mesenteric Artery, Superior/*innervation ; Rats ; Rats, Inbred Strains ; Transplantation, Heterotopic ; Transplantation, Isogeneic ; }, abstract = {The effects of denervation and warm ischaemia on quantitative and qualitative changes in small intestinal microflora following rat heterotopic small-bowel isotransplantation were assessed. Animals with Thiry-Vella fistula, but without transplants, acted as controls. Thirty and 40-fold increases in bacterial colony counts were seen in the isografts compared to controls at 2 and 7 days, respectively (P < 0.05). Aerobic faecal organisms predominated at 2 and 7 days, but an overgrowth of Flavobacterium meningosepticum occurred at 28 days in the transplanted and host bowels. The effect of warm ischaemia on intestinal microflora was assessed by the application of a microvascular clamp to the superior mesenteric artery for 90 min. The effect of denervation was assessed following microsurgical division of all nervous tissue around the superior mesenteric artery. After 7 days, lengths of jejunum and ileum were removed and intraluminal microflora assessed. The number of bacterial colonies isolated from the ileum in the warm ischaemia group was six times greater than the number in the control group, whereas no significant changes were seen in the upper bowel. In contrast, denervation led to a slight, but consistent, decrease in colony counts. These findings suggest that the increase in bacterial numbers in an isografted small bowel primarily results from warm ischaemia rather than from mesenteric denervation, and that physical aspects of the procedure may affect the development of sepsis following small-bowel transplantation.}, }
@article {pmid7956741, year = {1994}, author = {Cussac, C and Mounetou, E and Rapp, M and Madelmont, JC and Maurizis, JC and Labarre, P and Chollet, P and Chabard, JL and Godeneche, D and Baudry, JP}, title = {Disposition and metabolism of O6-alkylguanine-DNA alkyltransferase inhibitor in nude mice bearing human melanoma.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {22}, number = {4}, pages = {637-642}, pmid = {7956741}, issn = {0090-9556}, mesh = {Animals ; Autoradiography ; Carbon Radioisotopes ; Chromatography, High Pressure Liquid ; Feces/chemistry ; Female ; Guanosine/*analogs &amp; derivatives/metabolism/pharmacokinetics/urine ; Humans ; Melanoma/*drug therapy/*enzymology ; Methyltransferases/*antagonists &amp; inhibitors ; Mice ; Mice, Nude ; Neoplasm Transplantation ; O(6)-Methylguanine-DNA Methyltransferase ; Tissue Distribution ; }, abstract = {Tumor resistances to chloroethylnitrosourea (CENU) are mainly due to O6-alkylguanine-DNA alkyltransferase (AGT). Our laboratory has synthesized a new water-soluble AGT inhibitor. O6-benzyl-N-acetylguanosine (BNAG). We have shown that this compound is able to deplete AGT activity on M4Beu human melanoma cells and to enhance the antitumor power of CENU N'-[2-chloroethyl]-N-[2-(methylsulfonyl)ethyl]-N'-nitrosourea (cystemustine) towards the M4Beu melanoma grafted on nude mice. With a view to determining the best combination BNAG/CENUs conditions, we have studied the distribution and metabolism of BNAG in nude mice bearing M4Beu human melanoma. BNAG, labelled with carbon-14 on the benzyl group, was administered by single i.v. dose of 40 mg/kg. Blood analysis showed that the main radioactive compound was unchanged molecule, and only a small part was found as hippuric acid resulting from the metabolic cleavage of the benzyl group. BNAG and hippuric acid were mainly eliminated in the urine. Unchanged BNAG blood kinetics showed three phases: blood epuration (t1/2 (1) = 13 min), reabsorption and elimination (t1/2 (2) = 1.7 hr). This kinetic profile is probably due to an enterohepatic cycle. BNAG is distributed in several tissues (kidney, liver, skin, duodenum, colon, tumor) but not in the central nervous system, suggesting a poor blood-brain crossing. Because an important part of the administered dose is not metabolized, high unchanged BNAG level remains in most tissues, including M4Beu tumor, and AGT depletion can occur several hours after dosing.}, }
@article {pmid7931971, year = {1994}, author = {Baeten, CG and Konsten, J and Heineman, E and Soeters, PB}, title = {Dynamic graciloplasty for anal atresia.}, journal = {Journal of pediatric surgery}, volume = {29}, number = {7}, pages = {922-4; discussion 925}, doi = {10.1016/0022-3468(94)90016-7}, pmid = {7931971}, issn = {0022-3468}, mesh = {Adult ; Anal Canal/*surgery ; Anus, Imperforate/complications/*surgery ; Defecation/physiology ; *Electric Stimulation Therapy ; Electrodes, Implanted ; Fecal Incontinence/etiology/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Muscle Contraction/physiology ; Muscle, Skeletal/*transplantation ; }, abstract = {The aim of this study was to assess whether an electrically stimulated graciloplasty (dynamic graciloplasty) can achieve continence in nine patients with anal atresia (median age, 28 years; range, 18 to 40). As the first procedure, a gracilis muscle was transposed. Six weeks later, intramuscular electrodes were implanted and connected to a pulse generator. Eventually, the muscle was gradually trained, by electrical stimulation, to achieve fecal continence. Continence was obtained in five patients (55%). Manometry demonstrated an increase in mean anal pressure, from 36 mm Hg (without stimulation) to 52 mm Hg (with stimulation), after 8 weeks (mean increase, 16 mm Hg, [95% confidence interval, 8, 24 mm Hg; n = 9; P < .01). Failures resulted from a noncontracting distal part of the gracilis muscle (in three patients) and a nondistending rectum (in one patient). We conclude that dynamic graciloplasty can achieve continence in a substantial number of patients with thus-far untreatable incontinence after surgical correction for anal atresia.}, }
@article {pmid8086390, year = {1994}, author = {Ottolenghi, A and Sulpasso, M and Bianchi, S and Bettili, G and Salloum, A and Liber, H}, title = {Ectopic anus in childhood.}, journal = {European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie}, volume = {4}, number = {3}, pages = {145-150}, doi = {10.1055/s-2008-1066089}, pmid = {8086390}, issn = {0939-7248}, mesh = {Adolescent ; Anal Canal/*abnormalities/physiopathology/surgery ; Child ; Child, Preschool ; Congenital Abnormalities/epidemiology/surgery ; Constipation/etiology ; Fecal Incontinence/etiology ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Perineum/abnormalities ; Time Factors ; Vulva/abnormalities ; }, abstract = {The treatment of ten cases of ectopic anus is presented in this paper. The association of constipation with perineal anus due to alignment disturbance of the external sphincter triple loop system during evacuation has been described by Hendren (1978), Leape and Ramenofsky (1978), Upadhyaya (1984) et al. Hendren, Leape and Ramenofsky described two valid surgical techniques for this association. In this paper we describe the effect of non-invasive treatment in patients affected by symptomatic "primary" perineal anus. We also describe the effect of posterior anal transplant via the perineum in six infants and children with vulvar anus. This approach gave good results within three months without having to perform more complex operative techniques (Peña for example). Posterior anal transplant leads not only to an esthetic improvement but also to an improvement in fecal continence, which is sometimes deficient due to reduced anorectal angulation. It appears to us that an adequate perineal spur plays an important complementary role in the complex mechanism which controls fecal continence.}, }
@article {pmid8030086, year = {1994}, author = {Van Camp, JM and Drongowski, R and Gorman, R and Altabba, M and Hirschl, RB and Coran, AG}, title = {Colonization of intestinal bacteria in the normal neonate: comparison between mouth and rectal swabs and small and large bowel specimens.}, journal = {Transplantation proceedings}, volume = {26}, number = {3}, pages = {1681}, pmid = {8030086}, issn = {0041-1345}, mesh = {Aging/*physiology ; Animals ; Animals, Newborn ; Feces/microbiology ; Intestinal Mucosa/*microbiology ; Intestine, Large ; Intestine, Small ; Mouth Mucosa/*microbiology ; Organ Specificity ; Rabbits ; Rectum ; Reference Values ; }, }
@article {pmid8030078, year = {1994}, author = {Kiyozaki, H and Kobayashi, E and Toyama, N and Mori, Y and Miyata, M}, title = {Graft physiology after segmental small bowel transplantation in the rat.}, journal = {Transplantation proceedings}, volume = {26}, number = {3}, pages = {1662}, pmid = {8030078}, issn = {0041-1345}, mesh = {Animals ; Bile Acids and Salts/analysis ; Feces/chemistry ; Ileum/physiology/transplantation ; Intestine, Small/*physiology/*transplantation ; Jejunum/physiology/transplantation ; Lipids/analysis ; Male ; Muscle, Smooth/physiology/transplantation ; Rats ; Rats, Inbred Lew ; Transplantation, Isogeneic ; Weight Gain ; }, }
@article {pmid8029920, year = {1994}, author = {Ye, Y and Niekrasz, M and Welsh, R and Kosanke, S and Maxwell, C and Zuhdi, N and Cooper, DK}, title = {A practical study of zoonoses that could complicate pig-to-man organ transplantation.}, journal = {Transplantation proceedings}, volume = {26}, number = {3}, pages = {1312}, pmid = {8029920}, issn = {0041-1345}, mesh = {Animals ; Feces/parasitology ; Helminthiasis/*transmission ; *Helminthiasis, Animal ; Helminths/isolation &amp; purification ; Humans ; Swine ; *Swine Diseases ; *Transplantation, Heterologous ; *Zoonoses ; }, }
@article {pmid8020819, year = {1994}, author = {Sallie, R and Chiyende, J and Tan, KC and Bradley, D and Portmann, B and Williams, R and Mowat, AP and Mieli-Vergani, G}, title = {Fulminant hepatic failure resulting from coexistent Wilson's disease and hepatitis E.}, journal = {Gut}, volume = {35}, number = {6}, pages = {849-853}, pmid = {8020819}, issn = {0017-5749}, mesh = {Base Sequence ; Child ; DNA, Viral/analysis ; Feces/microbiology ; Female ; Hepatic Encephalopathy/*etiology/surgery ; Hepatitis E/*complications ; Hepatitis E virus/isolation &amp; purification ; Hepatolenticular Degeneration/*complications ; Humans ; Liver/pathology ; Liver Transplantation ; Molecular Sequence Data ; Polymerase Chain Reaction ; RNA, Viral/analysis ; }, abstract = {Fulminant hepatic failure resulting from hepatitis E and coexistent Wilson's disease was diagnosed in a six year old girl six weeks after returning from a holiday in India. Wilson's disease was diagnosed on the basis of histological evidence of hepatocellular copper deposition, confirmed by biochemical estimation of liver copper concentration. Although severely damaged, the liver was non-cirrhotic. Hepatitis E virus (HEV) was diagnosed by nested polymerase chain reaction, the specificity of which was confirmed by direct sequencing of amplified DNA. Replication of HEV within the liver at the time of diagnosis was confirmed by selective amplification of the antigenomic strand of the virus obtained from total liver RNA. The patient had an orthotopic liver transplantation without recurrence of hepatitis and remains well at 19 months. Viral excretion, recorded by serial amplification of HEV RNA extracted from stool samples, persisted for 30 days after liver grafting. Severe vitiligo, present preoperatively, dramatically improved after liver grafting and institution of immunosuppressive treatment. This case suggests that viral infection may play a part in the acute decompensation seen in some cases of Wilson's disease.}, }
@article {pmid8070947, year = {1994}, author = {Shatari, T and Sugiyama, Y and Teramoto, T and Kitajima, M and Minamitani, H}, title = {Reconstruction of anal function by transposed gracilis muscle with electrical stimulation: rabbit model.}, journal = {The International journal of artificial organs}, volume = {17}, number = {4}, pages = {240-244}, pmid = {8070947}, issn = {0391-3988}, mesh = {Anal Canal/physiology/*surgery ; Animals ; Defecation/physiology ; Electric Stimulation ; Male ; Muscle Contraction ; Muscles/*transplantation ; Pressure ; Rabbits ; }, abstract = {For the reconstruction of anal function for fecally incontinent patients, it could be practicable to transpose the gracilis muscle around the anal canal, with electrical stimulation to maintain contraction. It is necessary to keep continuous tonus, so tetanic contraction or "summation" would be essential for fecal continence, with a stimulation which permits prolonged contraction. Transposition of the gracilis muscle around the rectum was performed in thirteen Japanese white male rabbits. The muscles of the conditioning group (n = 8) were stimulated at 10 Hz for 6 weeks before the procedure. By stimulation at 15 Hz, a low frequency to permit prolonged contraction, the neoanal pressure increased maximally to 134.2 +/- 55.6 cmH2O (mean +/- s.d.) in the conditioning group, and to 115.0 +/- 37.1 cmH2O in the non-conditioning group (n = 5) (N.S.). But, the basal pressure with stimulation rose 82.3 +/- 12.4% (mean +/- s.d.) of the increase in the conditioning group, while that of the non-conditioning group remained at resting pressure (p < 0.001). The conditioning made it possible for the rabbit's gracilis muscle to create anal pressure with a sufficient rise in the basal pressure at a frequency permitting prolonged contraction.}, }
@article {pmid8140633, year = {1994}, author = {Ye, Y and Niekrasz, M and Kosanke, S and Welsh, R and Jordan, HE and Fox, JC and Edwards, WC and Maxwell, C and Cooper, DK}, title = {The pig as a potential organ donor for man. A study of potentially transferable disease from donor pig to recipient man.}, journal = {Transplantation}, volume = {57}, number = {5}, pages = {694-703}, doi = {10.1097/00007890-199403150-00011}, pmid = {8140633}, issn = {0041-1337}, mesh = {Animal Feed/toxicity ; Animals ; Biopsy ; Feces/microbiology/parasitology ; Female ; Heart ; Humans ; Kidney/blood supply ; Liver ; Male ; Swine/microbiology/parasitology/*physiology ; *Tissue Donors ; Transplantation, Heterologous/pathology/*physiology ; Vasculitis/pathology ; Zoonoses/microbiology/parasitology/*transmission ; }, abstract = {Ten pigs, reared in an unmodified laboratory animal house environment, have been investigated to ascertain the incidence of diseases or disorders, including infection, neoplasia, or metabolic abnormalities, that might preclude the transplantation of major organs from the pig to man. Noninvasive studies were performed in the second month of life (study 1) and repeated after an interval that varied between 3 and 5 1/2 months (study 2). Necropsy was then performed as a means of assessing the accuracy of the 2 screening examinations. A total of 150 tests were performed on each pig. At both studies the feces contained cysts and/or trophozoites of several parasites, all of which were considered commensals. No other organisms potentially infective for man were identified either at study or at necropsy. Neither congenital anomalies nor malignant neoplasia was found at necropsy. However, in 2 pigs a vasculitis of uncertain etiology was present in the kidneys on microscopic examination, and in one of these the same condition affected the heart. This pathology was suspected neither from the screening examinations nor from the macroscopic appearance of these organs. Biopsy and microscopic examination would therefore appear to be essential before any organ is transplanted into a human.}, }
@article {pmid8204447, year = {1994}, author = {Hoppe, JE and Klingebiel, T and Niethammer, D}, title = {Selection of Candida glabrata in pediatric bone marrow transplant recipients receiving fluconazole.}, journal = {Pediatric hematology and oncology}, volume = {11}, number = {2}, pages = {207-210}, doi = {10.3109/08880019409141658}, pmid = {8204447}, issn = {0888-0018}, mesh = {Adolescent ; Bone Marrow Transplantation/*adverse effects ; Candida/*drug effects ; Child ; Feces/microbiology ; Female ; Fluconazole/*therapeutic use ; Humans ; Infant ; Longitudinal Studies ; Male ; Mouth/microbiology ; }, abstract = {We observed an alarmingly high rate (5/16 patients; 31.3%) of orointestinal colonization with Candida glabrata--often in high numbers--in pediatric bone marrow transplant recipients receiving fluconazole as antifungal prophylaxis. This selection is probably due to the intrinsically low susceptibility of C. glabrata to fluconazole.}, }
@article {pmid8161624, year = {1994}, author = {Samore, MH and DeGirolami, PC and Tlucko, A and Lichtenberg, DA and Melvin, ZA and Karchmer, AW}, title = {Clostridium difficile colonization and diarrhea at a tertiary care hospital.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {18}, number = {2}, pages = {181-187}, doi = {10.1093/clinids/18.2.181}, pmid = {8161624}, issn = {1058-4838}, mesh = {Aged ; Anti-Bacterial Agents/adverse effects ; Boston/epidemiology ; Clostridioides difficile/*isolation &amp; purification ; Clostridium Infections/*epidemiology/etiology ; Cross Infection/*epidemiology/etiology/*microbiology ; Diarrhea/*epidemiology/etiology/*microbiology ; Feces/microbiology ; Female ; Hospitals, Teaching ; Humans ; Male ; Middle Aged ; Patient Transfer ; Prospective Studies ; Rectum/microbiology ; Risk Factors ; }, abstract = {Clostridium difficile is the major identifiable infectious cause of nosocomial diarrhea. A prospective study was conducted at New England Deaconess Hospital (Boston) to examine risk factors for C. difficile carriage at both admission and follow-up. Specimens from patients admitted to two wards (one medical, one surgical) and three intensive care units (two surgical, one medical) were cultured weekly until discharge. For 89 (18%) of 496 patient admissions, at least one culture was positive. The prevalence of culture positivity within 72 hours of admission was 11%. Risk factors for culture positivity at admission were prior C. difficile diarrhea (adjusted odds ratio [OR] = 9.5), renal insufficiency (OR = 6.7), and recent hospitalization elsewhere (OR = 3.1). Fifteen percent of patients for whom initial cultures were negative and for whom follow-up cultures were performed acquired C. difficile. Admission to the vascular surgery service (relative risk [RR] = 2.3) and liver transplantation (RR = 4.2) were significant risk factors for C. difficile acquisition. Patients asymptomatically colonized on admission had very low risk (1 in 44) for subsequent development of C. difficile diarrhea. In contrast, nine (47%) of 19 patients who acquired toxigenic strains developed C. difficile diarrhea, a finding suggesting that progression to diarrhea occurs early after acquisition or does not occur at all. The relatively high prevalence of culture positivity at admission may be characteristic of tertiary care hospitals and adds to the difficulty of controlling this nosocomial pathogen.}, }
@article {pmid8155502, year = {1994}, author = {Avril, M and Hartmann, O and Valteau-Couanet, D and Brugieres, L and Kalifa, C and Lemerle, J}, title = {Antiinfective prophylaxis with ceftazidime and teicoplanin in children undergoing high-dose chemotherapy and bone marrow transplantation.}, journal = {Pediatric hematology and oncology}, volume = {11}, number = {1}, pages = {63-73}, doi = {10.3109/08880019409141902}, pmid = {8155502}, issn = {0888-0018}, mesh = {Adolescent ; Antifungal Agents/therapeutic use ; Bacteremia/etiology/*prevention &amp; control ; *Bone Marrow Transplantation ; Ceftazidime/*administration &amp; dosage/adverse effects ; Child ; Child, Preschool ; Combined Modality Therapy ; Feces/microbiology ; Female ; Fever of Unknown Origin/etiology ; Humans ; Male ; Teicoplanin/*administration &amp; dosage/adverse effects ; }, abstract = {Sixty children treated for solid tumors with high-dose chemotherapy followed by bone marrow transplantation were randomly assigned to one of two antibiotic protocols. Group A received prophylaxis consisting of ceftazidime plus teicoplanin beginning before the onset of aplasia and fever; group B received exactly the same antibiotic regimen but beginning at the onset of fever. The two groups were compared in terms of the rate of septicemia, fever of unknown origin, the time-lapse before the appearance of septicemia, the sensitivity of the causative organisms to the antibiotics, the effect of the latter on the intestinal flora, and the rate of fungal infections. The incidence of septicemia was significantly lower in group A (6.6%) than in group B (24.0%), mainly due to the prevention of episodes of early onset. Similarly, the appearance of the first episode of fever was delayed in group A, and the overall duration was reduced. Amphotericin B was prescribed empirically with the same rule in both groups, but three children in group A did not require amphotericin B. The effect on the intestinal flora was similar in the two groups; it must, however, be closely monitored so that the presence of potential pathogens can be dealt with appropriately.}, }
@article {pmid8128716, year = {1994}, author = {Kennedy, HL}, title = {Stimulated gracilis neosphincter clinical trial.}, journal = {The Western journal of medicine}, volume = {160}, number = {1}, pages = {77}, pmid = {8128716}, issn = {0093-0415}, mesh = {Anal Canal/*surgery ; Clinical Trials as Topic ; Electric Stimulation ; Fecal Incontinence/*surgery ; Humans ; Muscles/*transplantation ; Prostheses and Implants ; }, }
@article {pmid8127942, year = {1994}, author = {Zuk, MM and Rihter, BD and Kenney, ME and Rodgers, MA and Kreimer-Birnbaum, M}, title = {Pharmacokinetic and tissue distribution studies of the photosensitizer bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) in normal and tumor-bearing rats.}, journal = {Photochemistry and photobiology}, volume = {59}, number = {1}, pages = {66-72}, doi = {10.1111/j.1751-1097.1994.tb05002.x}, pmid = {8127942}, issn = {0031-8655}, support = {CA 46281/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Male ; Metalloporphyrins/*pharmacokinetics ; Muscles/metabolism ; Neoplasms, Experimental/*metabolism ; Organosilicon Compounds/*pharmacokinetics ; Radiation-Sensitizing Agents/*pharmacokinetics ; Rats ; Rats, Inbred F344 ; Skin/metabolism ; Tissue Distribution ; }, abstract = {Bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) is a representative of a group of naphthalocyanine derivatives with spectral and photophysical properties that make them attractive candidates for photodynamic therapy (PDT). Tissue distributions were studied in normal and in tumor-bearing rats as a function of time following intravenous injection of isoBOSINC as a suspension in 10% Tween 80 in saline. The dose studied was 0.25 mg/kg of body weight. The compound isoBOSINC was isolated from several tissues and organs, as well as tumors and peritumoral muscles and skin, and quantitated by a high-performance liquid chromatographic technique. The tumor model, an N-(4-[5-nitro-2-furyl]-2-thiazolyl)formamide (FANFT)-induced urothelial cell carcinoma, was transplanted into the hind legs of Fischer 344 rats. The dye was retained in tumors at higher concentrations than in all tissues and organs examined, except for spleen and liver. The highest concentration ratio of dye in tumor versus peritumoral muscle (24.5) occurred 9 h after injection. Serum clearance of isoBOSINC showed similar kinetic behavior for both groups of rats, with a t 1/2 of elimination of approximately 10 h. At 7 and 14 days postinjection, the levels of dye found in testes were generally higher than in most other tissues, except spleen and liver. Concentrations of isoBOSINC were either very low or not detectable in rat brain. Trace amounts of the dye were excreted in the urine, and by day 14 approximately 17% of the dose was accounted for in the feces. The significant levels of the drug in tumors, as well as the excellent ratios of tumor-to-muscle concentration observed, have promising implications for PDT of tumors.}, }
@article {pmid8124972, year = {1994}, author = {Bion, JF and Badger, I and Crosby, HA and Hutchings, P and Kong, KL and Baker, J and Hutton, P and McMaster, P and Buckels, JA and Elliott, TS}, title = {Selective decontamination of the digestive tract reduces gram-negative pulmonary colonization but not systemic endotoxemia in patients undergoing elective liver transplantation.}, journal = {Critical care medicine}, volume = {22}, number = {1}, pages = {40-49}, doi = {10.1097/00003246-199401000-00011}, pmid = {8124972}, issn = {0090-3493}, mesh = {Adult ; Anti-Bacterial Agents/*therapeutic use ; Critical Care ; Digestive System Diseases/*microbiology/physiopathology/*prevention &amp; control ; Endotoxins/blood ; Feces/microbiology ; Female ; Gram-Negative Bacterial Infections/mortality/physiopathology/*prevention &amp; control ; Humans ; *Liver Transplantation ; Lung Diseases/*microbiology/*prevention &amp; control ; Male ; Middle Aged ; Postoperative Complications/*microbiology/physiopathology/*prevention &amp; control ; Prospective Studies ; Severity of Illness Index ; }, abstract = {OBJECTIVE: To examine the effect of selective antibiotic decontamination of the digestive tract in patients undergoing elective orthotopic liver transplantation.<br><br>DESIGN: Prospective, randomized, concurrent allocation to either selective decontamination or standard antibiotic prophylaxis.<br><br>SETTING: Operating theater and intensive care unit at a tertiary referral, university teaching hospital.<br><br>PATIENTS: Fifty-nine adult patients were recruited into the study and underwent liver transplantation.<br><br>INTERVENTIONS: Thirty-two patients were randomized to standard treatment (control group) and 27 patients were randomized to receive selective decontamination. After early deaths and exclusions, 31 controls and 21 decontamination patients were available for analysis.<br><br>MEASUREMENTS AND MAIN RESULTS: Portal and systemic endotoxemia, colonization and infection rates, severity of illness (organ system failures, Acute Physiology and Chronic Health Evaluation II score, Therapeutic Intervention Scoring System score), antibiotic costs, and hospital survival rates were measured. Selective decontamination significantly reduced pulmonary infections and enteric, aerobic, and Gram-negative bacillary colonization without facilitating the emergence of resistant organisms, but selective decontamination had no effect on endotoxemia or the development of organ system failures. The financial costs of the selective decontamination regimen outweighed the advantages gained from an associated reduction in antibiotic usage.<br><br>CONCLUSION: The failure of selective decontamination to enhance survival rates in many studies of the regimen in critically ill patients may, in part, be related to the inability of selective decontamination to abolish endotoxemia.}, }
@article {pmid8031021, year = {1994}, author = {el Moussaoui, A and Aboutaieb, R and Joual, A and el Mrini, M and Meziane, F and Benjelloun, S}, title = {[Perineo-scrotal gangrene. Analysis of 49 cases].}, journal = {Annales d'urologie}, volume = {28}, number = {3}, pages = {142-6; discussion 147}, pmid = {8031021}, issn = {0003-4401}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Combined Modality Therapy ; Comorbidity ; Gangrene/drug therapy/*epidemiology/etiology/surgery ; Genital Diseases, Male/drug therapy/epidemiology/etiology/surgery ; Humans ; Male ; Middle Aged ; Morocco/epidemiology ; Perineum/*pathology ; Scrotum/*pathology ; Skin Transplantation ; Surgical Flaps ; Survival Rate ; Time Factors ; }, abstract = {Perineo-scrotal gangrene is a necrotizing infection of the tissues of the perineum and scrotum. It accounts for 0.6% of our hospitalizations. The commonest etiology is urologic (86% of our cases). A proctologic origin was found in 6%, while the condition appeared to be primary in 8%. Concomitant diseases were found in 37% with diabetes the commonest. The diagnosis is clinically evident. The majority of patients are seen late (5 to 10 days) and the necrotizing process spreads rapidly. This is a multidisciplinary emergency, requiring intensive care, antibiotics, surgical excision of all necrotic tissues and possible urinary and/or fecal diversion. Extensive skin loss requires surgical cutaneous reconstruction procedures. The prognosis is severe, with a 12% mortality rate in our series.}, }
@article {pmid7876720, year = {1994}, author = {Rosen, HR and Feil, W and Novi, G and Zöch, G and Dahlberg, S and Schiessel, R}, title = {The electrically stimulated (dynamic) graciloplasty for faecal incontinence--first experiences with a modified muscle sling.}, journal = {International journal of colorectal disease}, volume = {9}, number = {4}, pages = {184-186}, pmid = {7876720}, issn = {0179-1958}, mesh = {*Electric Stimulation Therapy ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Muscle, Skeletal/*transplantation ; Rectum/*surgery ; Reoperation ; Thigh/surgery ; Treatment Outcome ; }, abstract = {Continence following the gracilis stimulated neosphincter reconstruction after total rectal excision is inferior to that obtained in the presence of an intact anal canal. We describe a modification of the alpha loop in which the tendon is brought through the belly of the gracilis muscle. The results in three patients are presented.}, }
@article {pmid7710854, year = {1994}, author = {Wei, YY and Chung, C}, title = {Analysis of elemental absorption and excretion in mice bearing malignant ascites.}, journal = {Biological trace element research}, volume = {43-45}, number = {}, pages = {397-403}, pmid = {7710854}, issn = {0163-4984}, mesh = {Animals ; Ascites/*metabolism ; Diet ; Feces/chemistry ; Intestinal Absorption ; Intestine, Small/chemistry ; Kidney/chemistry ; Male ; Mice ; Mice, Inbred ICR ; Neoplasm Transplantation ; Neutron Activation Analysis ; Sarcoma 180/*metabolism/pathology ; Trace Elements/*metabolism/pharmacokinetics/urine ; }, abstract = {Feces, kidney, and small intestine were sampled from the mice bearing malignant ascites at different stages of tumor growth to investigate the kinetics of elemental distribution in the body. The contents of 14 elements in samples were determined by instrumental neutron activation analysis (INAA). The elements Br, Cl, Cu, Na, Se, and Zn increased, whereas Mn and Rb decreased in kidney with the growth of the tumor. The elements Cl, Na, and Fe, however, appeared to have significantly different behavior in the small intestine.}, }
@article {pmid7709833, year = {1994}, author = {Bos, NA and Bun, JC and Bijma, H and Cebra, ER and Cebra, JJ and Deenen, GJ and van der Cammen, MJ and Kroese, FG}, title = {Analysis of IgA-producing hybridomas derived from peritoneal B1 cells.}, journal = {Advances in experimental medicine and biology}, volume = {355}, number = {}, pages = {265-269}, doi = {10.1007/978-1-4615-2492-2_45}, pmid = {7709833}, issn = {0065-2598}, mesh = {Animals ; Antibodies, Bacterial/immunology ; Antibody Specificity ; B-Lymphocyte Subsets/cytology/*immunology/transplantation ; Cell Differentiation ; Cell Survival ; Chimera ; Feces/microbiology ; Humans ; Hybridomas/*immunology ; Immunoglobulin A/*biosynthesis ; Lymph Nodes/cytology ; Mesentery ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Peritoneal Cavity/cytology ; Plasma Cells/immunology ; Spleen/cytology/immunology ; }, }
@article {pmid7517256, year = {1994}, author = {Copelan, EA and Bechtel, TP and Klein, JP and Klein, JL and Tutschka, P and Kapoor, N and Featheringham, NC and Avalos, BR}, title = {Controlled trial of orally administered immunoglobulin following bone marrow transplantation.}, journal = {Bone marrow transplantation}, volume = {13}, number = {1}, pages = {87-91}, pmid = {7517256}, issn = {0268-3369}, support = {2 P30 CA 16058-61A1/CA/NCI NIH HHS/United States ; }, mesh = {Administration, Oral ; Anemia, Aplastic/surgery ; Bone Marrow Transplantation/*adverse effects/immunology ; Double-Blind Method ; Feces/chemistry ; Gastrointestinal Diseases/prevention &amp; control ; Graft vs Host Disease/prevention &amp; control ; Humans ; Immunoglobulin G/analysis ; Infection Control ; Leukemia/surgery ; Lymphoma/surgery ; gamma-Globulins/*administration &amp; dosage ; }, abstract = {Between May 1987 and September 1989, 72 patients undergoing marrow transplantation at a single institution were randomized to receive 50 mg/kg of a commercial gammaglobulin preparation or placebo daily in four divided doses for 28 days following transplantation. Patients receiving oral gammaglobulin had significantly increased concentrations of stool IgG (p = 0.01) compared with the placebo group. There was no difference in the amount of diarrhea, frequency of GVHD, duration of hospitalization or survival in the two groups. The present study demonstrates that orally administered IgG can survive passage through the gastrointestinal tract of bone marrow transplantation recipients but there was no effect of oral administration of immunoglobulin on morbidity or mortality following bone marrow transplantation.}, }
@article {pmid8136740, year = {1993}, author = {Troussard, X and Bauduer, F and Gallet, E and Freymuth, F and Boutard, P and Ballet, JJ and Reman, O and Leporrier, M}, title = {Virus recovery from stools of patients undergoing bone marrow transplantation.}, journal = {Bone marrow transplantation}, volume = {12}, number = {6}, pages = {573-576}, pmid = {8136740}, issn = {0268-3369}, mesh = {Adenovirus Infections, Human/etiology ; Adenoviruses, Human/*isolation &amp; purification ; Adult ; Bone Marrow Transplantation/*adverse effects ; Feces/microbiology ; Female ; Gastroenteritis/etiology ; Graft vs Host Disease/etiology ; Humans ; Male ; Risk Factors ; Rotavirus/*isolation &amp; purification ; Rotavirus Infections/etiology ; Transplantation, Autologous ; Transplantation, Homologous ; }, abstract = {Diarrhea in marrow transplant recipients is a frequent complication attributable to non-infectious events such as acute GVHD or infectious events such as viral gastroenteritis. Rotavirus and enteric adenovirus are the most frequent viral pathogens. To determine the frequency of these infections, we prospectively examined the stool specimens of 94 patients who underwent autologous BMT (34 cases) or allogeneic BMT (60 cases). Stool specimens were examined from patients twice weekly. Nineteen of the 94 patients were infected with viral pathogens. This study showed: (1) an incidence of viral gastroenteritis identical in autologous and allogeneic BMT (20%), (2) a persistent risk despite treatment in laminar air flow rooms, (3) a significant association with severe acute GVHD, and (4) a significant risk of multiple viral infections in autologous BMT recipients. Rotavirus and adenovirus are a cause of enteritis involvement in patients undergoing BMT and they may be underdiagnosed and confused with GVHD. Screening of stool specimens after BMT should be directed to prevention and treatment of these viral infections to decrease the morbidity and mortality associated with BMT.}, }
@article {pmid8249100, year = {1993}, author = {Meijssen, MA and Heineman, E and de Bruin, RW and Wolvekamp, MC and Marquet, RL and Molenaar, JC}, title = {Long-term survival of DLA-matched segmental small-bowel allografts in dogs.}, journal = {Transplantation}, volume = {56}, number = {5}, pages = {1062-1066}, doi = {10.1097/00007890-199311000-00002}, pmid = {8249100}, issn = {0041-1337}, mesh = {Animals ; Cyclosporine/blood ; Dogs ; Fats/metabolism ; *Graft Survival ; Histocompatibility Antigens/*immunology ; *Histocompatibility Antigens Class I ; Ileum/*transplantation ; Serum Albumin/analysis ; Survival Rate ; Transplantation, Homologous ; }, abstract = {The aim of this study was to investigate the combined effect of DLA matching and immunosuppressive therapy on the survival of segmental small-bowel allografts in dogs. Orthotopic segmental small-bowel transplantations (25 to 30% of total small bowel length) were performed in two stages: first a heterotopic segmental small bowel transplantation, followed after 5 to 8 weeks by a second-stage operation during which the heterotopic graft was placed in an orthotopic position and the native small bowel was resected. All dogs received cyclosporine immunosuppression. Control dogs (n = 4), subjected to total enterectomy, survived 37.3 +/- 7.1 days (mean +/- SEM). Recipients of DLA-mismatched small bowel grafts (n = 6) survived 113.2 +/- 37.0 days, which was a significantly shorter time than dogs with a DLA-matched graft (n = 6, 211.5 +/- 38.8 days, P < 0.05). None of the matched allografts was rejected during CsA treatment, whereas four of six mismatched grafts were (P < 0.05). The control dogs uniformly showed progressive weight loss, steatorrhea, and hypoalbuminemia. The dogs with DLA-mismatched grafts did not regain initial body weight, whereas animals with DLA-matched grafts recovered preoperative weight after 20 weeks. Both transplanted groups showed near-normal fecal fat excretions and constant serum albumin, cholesterol, and triglyceride levels, whereas serum total protein levels increased during follow-up. We conclude that segmental small bowel transplantation between DLA-matched donor-recipient pairs results in long-term survivors with an adequate nutritional status. This may have important implications for future living-related small-bowel transplantation.}, }
@article {pmid8239711, year = {1993}, author = {Robinson, WE and Ryan, DK and Wallace, GT}, title = {Gut contents: a significant contaminant of Mytilus edulis whole body metal concentrations.}, journal = {Archives of environmental contamination and toxicology}, volume = {25}, number = {4}, pages = {415-421}, doi = {10.1007/BF00214329}, pmid = {8239711}, issn = {0090-4341}, mesh = {Animals ; Artifacts ; Bivalvia/*chemistry ; Body Burden ; Intestines/*chemistry ; Metals/*analysis ; }, abstract = {Ingested matter can have a significant effect on whole body metal concentration measurements in Mytilus edulis. Depuration of mussels in clean seawater for 36 h prior to dissection eliminates most of these contaminating gut contents. Depuration followed by metal analyses is the most direct method of determining mussel tissue metal bioburdens. After being transplanted into a plume of primary treated sewage effluent in Salem Harbor, Massachusetts for 32 days, Al, Cr, and Fe concentrations in depurated mussels were significantly lower than those determined for either non-depurated mussels or for depurated mussels to which fecal concentrations of Al, Cr, and Fe were added back in. Although mathematical methods developed by both Ouellette (1978) and Boehm et al. (1988) could be applied to non-depurated mussels in order to correct for errors associated with gut metal contamination, these indirect methods were not as reliable as depuration prior to analysis.}, }
@article {pmid8242319, year = {1993}, author = {George, BD and Williams, NS and Patel, J and Swash, M and Watkins, ES}, title = {Physiological and histochemical adaptation of the electrically stimulated gracilis muscle to neoanal sphincter function.}, journal = {The British journal of surgery}, volume = {80}, number = {10}, pages = {1342-1346}, doi = {10.1002/bjs.1800801042}, pmid = {8242319}, issn = {0007-1323}, mesh = {Adaptation, Physiological ; Adolescent ; Adult ; Aged ; Anal Canal/abnormalities/*physiopathology/surgery ; Electric Stimulation ; Fecal Incontinence/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Muscle Contraction/physiology ; Muscles/*transplantation ; Pressure ; }, abstract = {The physiological and histochemical characteristics of the gracilis muscle were studied in 19 patients undergoing electrically stimulated gracilis neosphincter construction. Indications for surgery were faecal incontinence (n = 11) and reconstruction following sphincter excision or congenital absence (n = 8). Transposition of the gracilis muscle around the anal canal followed by chronic low-frequency electrical stimulation was associated with a shift in the frequency-response curve and a prolongation of the time-course of individual muscle twitches suggestive of transformation to a slow-twitch fatigue-resistant type. Temporary cessation of electrical stimulation resulted in a reversal of the frequency-response changes. Muscle biopsies taken before and a median of 80 (range 49-137) days after transposition and low-frequency electrical stimulation indicated a significant increase in the proportion of type 1 fibres and a significant decrease in their diameter. These results show that the human gracilis muscle is capable of physiological and histochemical adaptation to long-term neosphincter function.}, }
@article {pmid8225756, year = {1993}, author = {Khan, AI and Horii, Y and Tiuria, R and Sato, Y and Nawa, Y}, title = {Mucosal mast cells and the expulsive mechanisms of mice against Strongyloides venezuelensis.}, journal = {International journal for parasitology}, volume = {23}, number = {5}, pages = {551-555}, doi = {10.1016/0020-7519(93)90159-v}, pmid = {8225756}, issn = {0020-7519}, mesh = {Animals ; Bone Marrow Transplantation ; Disease Models, Animal ; Feces/parasitology ; Female ; Immunity, Innate/genetics ; Intestinal Mucosa/*immunology/parasitology ; Male ; Mastocytosis/*parasitology ; Mice ; Mice, Inbred C57BL/parasitology ; Mice, Inbred Strains/genetics/parasitology ; Mutation ; Strongyloidiasis/*complications/*immunology ; }, abstract = {The possible importance of mucosal mast cells in the expulsive mechanisms of mice against Strongyloides venezuelensis was examined. After a primary infection by subcutaneous inoculation with various doses into C57BL/6 mice, about 50% of the initial dose of infective larvae (L3) became adult worms and, regardless of the dose of infection, they were completely expelled by Day 12 with similar kinetics. Intestinal mastocytosis at the time of expulsion was comparable among groups given different doses of infection. A kinetic study after infection with 2000 L3 in C57BL/6 mice revealed that mastocytosis started from Day 8, rapidly reached a peak on Day 12, and then gradually decreased. The strongest mastocytosis was observed in the upper one sixth of the small intestine where the majority of adult worms parasitized. Over 80% of mast cells induced by the infection were located in the intestinal epithelial layer. When mast cell-deficient W/Wv and their normal littermate +/+ mice were infected with 1000 L3, expulsion was significantly delayed in W/Wv mice, though adult worms were eventually expelled by Day 18 in W/Wv mice. Delayed expulsion as well as defective mast cell responses of W/Wv mice were completely restored by bone marrow grafting 10 weeks prior to infection. These results show that, like S. ratti infection, intestinal mucosal mast cells are important in causing expulsion of S. venezuelensis.}, }
@article {pmid8358347, year = {1993}, author = {Sakahara, H and Saga, T and Endo, K and Hattori, N and Hosono, M and Kobayashi, H and Shirato, M and Yamamuro, T and Toyama, S and Arano, Y}, title = {In vivo instability of reduction-mediated 99mTc-labeled monoclonal antibody.}, journal = {Nuclear medicine and biology}, volume = {20}, number = {5}, pages = {617-623}, doi = {10.1016/0969-8051(93)90030-x}, pmid = {8358347}, issn = {0969-8051}, mesh = {Animals ; Antibodies, Monoclonal/chemistry/immunology/*metabolism ; Bone Neoplasms/immunology/metabolism ; Humans ; Indium Radioisotopes ; Iodine Radioisotopes ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Osteosarcoma/immunology/metabolism ; Oxidation-Reduction ; Radioimmunotherapy ; Technetium/chemistry/*pharmacokinetics ; Tissue Distribution ; }, abstract = {A murine monoclonal antibody that reacts with human osteogenic sarcoma (OST7) was reduced and directly labeled with 99mTc without any loss of immunoreactivity. No fragmentation of the antibody was detected by high performance liquid chromatography after the labeling. However, SDS-PAGE analysis of the labeled antibody demonstrated the presence of low molecular weight species. Although more than 95% of the radioactivity remained bound at the antibody after incubation with human serum for 24 h, 99mTc-labeled OST7 was cleared faster from the circulation than 125I-labeled OST7 or 111In-labeled OST7 in mice. Urinary and fecal excretion of 99mTc were higher than those of 125I. When the 125I-labeled antibody was dual-labeled with 99mTc, the blood clearance of 99mTc was faster than that of 125I, suggesting release of 99mTc from the antibody in vivo. 99mTc-labeled OST7, however, gave a higher tumor-to-blood ratio than 125I- or 111In-labeled OST7 in mice bearing human osteogenic sarcoma. The 99mTc-labeled antibody prepared by the direct method was unstable in vivo, but retained a good tumor targeting ability.}, }
@article {pmid8268584, year = {1993}, author = {Shatari, T and Teramoto, T and Watanabe, M and Kitajima, M and Minamitani, H}, title = {How to convert the rabbit gracilis muscle into a neoanal sphincter.}, journal = {ASAIO journal (American Society for Artificial Internal Organs : 1992)}, volume = {39}, number = {3}, pages = {M486-8}, pmid = {8268584}, issn = {1058-2916}, mesh = {Anal Canal/physiopathology/*surgery ; Animals ; Electric Stimulation/methods ; Humans ; Infant, Newborn ; Male ; Muscle Contraction/*physiology ; Muscle Tonus/physiology ; Muscles/physiopathology/*transplantation ; Rabbits ; }, abstract = {For reconstruction of anal function in fecally incontinent patients, transposition of the gracilis muscle around the anal canal, with electrical stimulation to maintain contraction, seems practical. But the fast-twitch gracilis muscle is incapable of prolonged contraction without fatigue. Furthermore, the muscle must keep some tension between each stimulus. When the pressure decreases even transiently between stimuli, the neoanus cannot maintain continence. To fulfill these criteria, the neoanal sphincter must be stimulated at a frequency that can induce sufficient summation. We demonstrated that conditioning with long-term electrical stimulation will induce such summation at low frequency. The nerve to the gracilis muscle of rabbits was continuously stimulated at 5 Hz and 10 Hz for 4 to 8 weeks. This conditioning reduced the frequency necessary for summation, and conditioning at 10 Hz for 6 or 8 weeks induced sufficient summation (fusion index [FI] > 90%) at 20 Hz. The muscles conditioned at 10 Hz for 8 weeks showed sufficient summation (FI = 81%) at 15 Hz, a frequency that produced muscle contraction without fatigue, since even unconditioned muscle will remain contracted at 10 Hz without fatigue for 8 weeks. It is concluded that conditioning at 10 Hz for longer than 6 weeks produces enough summation at a low frequency stimulation to permit prolonged contraction.}, }
@article {pmid8507064, year = {1993}, author = {Renz, BM and Sherman, R}, title = {Exposure of buttock burn wounds to stool in scald-abused infants and children: stool-staining of eschar and burn wound sepsis.}, journal = {The American surgeon}, volume = {59}, number = {6}, pages = {379-383}, pmid = {8507064}, issn = {0003-1348}, mesh = {Bacteremia/microbiology ; Burns/*microbiology/*pathology/surgery ; Buttocks/*injuries/microbiology/pathology/surgery ; Catheterization ; Cause of Death ; *Child Abuse ; Child, Preschool ; Dermatologic Surgical Procedures ; Diarrhea/microbiology/pathology ; *Feces/microbiology ; Humans ; Infant ; Perineum/injuries/microbiology ; Prospective Studies ; Rectum ; Skin/*microbiology/*pathology ; Skin Transplantation/pathology ; Survival Rate ; Wound Healing ; *Wound Infection ; }, abstract = {Between July 1, 1987 and June 30, 1990, 30 consecutive deliberately scalded children with buttock involvement were prospectively studied. Mean age was 22.5 months. Mean burn size was 18.1 per cent TBSA (total body surface area). Thirty per cent (n = 9) had diarrhea complicate their wound or autograft care. For those requiring surgery for their buttock/perineal burns, various combinations of preoperative mechanical bowel prep, oral antibiotics, postoperative occlusive intrarectal catheter, nothing-by-mouth, and rigid postoperative positioning did not protect buttock wounds and autografts from stool. Four patients had stool staining of the superficial burn wound exudate, none of whom developed burn wound sepsis or died. Four (13.3%) patients with a mean burn size of 32.3 per cent TBSA, diarrhea, and burns involving the buttock, perineum, and external genitalia died of burn wound sepsis, three of whom had deep stool staining of their burn wound and Gram-positive bacteremia. Buttock burn wounds should be examined carefully and frequently for the presence of deep stool staining, an ominous predictor of burn wound sepsis and death. Such wounds, if present, should be emergently excised.}, }
@article {pmid8489105, year = {1993}, author = {Renz, BM and Sherman, R}, title = {Abusive scald burns in infants and children: a prospective study.}, journal = {The American surgeon}, volume = {59}, number = {5}, pages = {329-334}, pmid = {8489105}, issn = {0003-1348}, mesh = {Burns/complications/*surgery ; Buttocks/injuries/surgery ; *Child Abuse ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Nutrition Disorders/complications ; Prospective Studies ; Skin Transplantation ; Staphylococcal Infections/etiology ; Wound Infection/microbiology ; }, abstract = {Between July 1, 1987 and June 30, 1990, 30 consecutive deliberately scalded children were studied prospectively. Purposes of the study were to characterize the scald-abused child and address the management problems specific to this group. Mean age was 22.5 months. Many had preburn growth retardation. Mean burn size was 18.1 per cent of the total body surface area and 37 per cent required a surgical procedure for their scald. All 30 children had burns on the buttocks. Four (13.3%) had other injuries. Eighty per cent of patients had at least one complication. In 30 per cent, diarrhea complicated nutrition support, wound, or autograft care. Four (13.3%) patients with a mean burn size of 32.3 per cent of the total body surface area, diarrhea, and burns involving the buttocks, perineum, and external genitalia died of burn wound sepsis; three of these had Gram-positive bacteremia (Staphylococcus aureus and enterococcus). Burn wounds exposed to the fecal stream (buttocks) should be examined carefully and frequently for signs of infection, particularly in those patients with diarrhea.}, }
@article {pmid8337888, year = {1993}, author = {Konsten, J and Baeten, CG and Spaans, F and Havenith, MG and Soeters, PB}, title = {Follow-up of anal dynamic graciloplasty for fecal continence.}, journal = {World journal of surgery}, volume = {17}, number = {3}, pages = {404-8; discussion 408-9}, pmid = {8337888}, issn = {0364-2313}, mesh = {Adult ; Aged ; Anal Canal/physiopathology/*surgery ; Case-Control Studies ; Electric Stimulation/instrumentation ; Electrodes, Implanted ; Electromyography ; Feasibility Studies ; Fecal Incontinence/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Middle Aged ; Muscle Contraction/physiology ; Muscles/physiopathology/*transplantation/ultrastructure ; Myofibrils/ultrastructure ; Pressure ; Surgical Flaps/adverse effects/*methods ; }, abstract = {The feasibility of anal dynamic graciloplasty (transposition of the gracilis muscle and subsequent implantation of a stimulation device) to restore continence, was assessed in a case-control study of 26 patients with severe fecal incontinence. It was shown that anal dynamic graciloplasty is capable of achieving the sphincter tone of healthy persons, as stimulated graciloplasty increased anal pressure from 46 mmHg without stimulation to 65 mmHg with stimulation (mean increase 19 mmHg; 95% confidence interval 13, 25; n = 25; p < 0.01). Time to retain a 250-ml phosphate enema increased from 52 seconds before to 204 seconds after 8 weeks of electrical stimulation (mean increase 151 seconds; 95% confidence interval 61, 241; n = 25; p < 0.01). Complete fecal continence was achieved in 17 patients (65%); two of these patients developed a wound infection, but one of the two realized continence without stimulation and the other patient became continent after reimplantation. Three other patients improved after anal dynamic graciloplasty, but infection necessitated removal of the stimulation device. One patient developed a fistula. Failures were encountered in five patients. Although our long-term follow-up results suggest a learning curve, it is concluded that electrical stimulation improves the results of conventional graciloplasty and avoids construction of a colostomy.}, }
@article {pmid8490811, year = {1993}, author = {Abrams-Ogg, AC and Kruth, SA and Carter, RF and Dick, JE and Valli, VE and Kamel-Reid, S and Dubé, ID}, title = {Clinical and pathological findings in dogs following supralethal total body irradiation with and without infusion of autologous long-term marrow culture cells.}, journal = {Canadian journal of veterinary research = Revue canadienne de recherche veterinaire}, volume = {57}, number = {2}, pages = {79-88}, pmid = {8490811}, issn = {0830-9000}, mesh = {Animals ; Bacterial Infections/drug therapy/etiology ; Bone Marrow Diseases/*surgery ; *Bone Marrow Transplantation/adverse effects ; Cell Count ; Cells, Cultured ; *Disease Models, Animal ; *Dogs ; Follow-Up Studies ; *Hematopoiesis/radiation effects ; Hemorrhage/etiology/therapy ; Lymphoma/surgery ; Platelet Transfusion ; Whole-Body Irradiation ; }, abstract = {We developed a canine model for autologous bone marrow transplantation (AuBMT) with long-term marrow culture (LTMC) cells. Marrow was harvested from nine normal dogs. Harvests from dogs 2-7 were placed into 21 day LTMC. Cells in LTMC from dogs 4-7 were labelled with the neomycin phosphotransferase gene neo. Dogs were given 60Co total body irradiation (TBI) and then infused with LTMC cells: dog 1 received 500 cGy TBI and 2.08 x 10(8)/kg uncultured marrow cells. Dogs 2-7 received 600-800 cGy TBI and 0.07-0.45 x 10(8)/kg LTMC cells. Dogs 8 and 9 received 600 and 800 cGy TBI, respectively, but no infusion of marrow or LTMC cells. For all dogs, profound myelosuppression developed during week 1 and pyrexia developed during week 2. Enrofloxacin was given from one day before TBI until a peripheral neutrophil count > 1.0 x 10(9)/L was achieved, which eliminated Escherichia coli from feces. Dogs 1, 2 and 5-9 also received gentamicin and/or combination beta-lactam antibiotics. Numerous platelet transfusions were needed to control hemorrhages in all dogs except dog 1. Dog 1 achieved neutrophils > 1.0 x 10(9)/L on day 15, while dogs 2 and 5-9 achieved this count on days 33-48. Dogs 3 and 4 died on days 17 and 18, respectively, of beta-hemolytic streptococcal sepsis and hemorrhage, with no evidence of hematopoiesis at necropsy. The marker gene, neo, was documented in lymphoid and myeloid cells of dogs 5-7 up to 21 months post-AuBMT. Our studies indicate that dogs can recover following supralethal TBI and can survive the delayed engraftment associated with AuBMT using LTMC cells, if they receive intensive platelet and antimicrobial therapy. Used prophylactically for such therapy, enrofloxacin achieved selective intestinal decontamination, but did not prevent sepsis when used as the sole antimicrobial agent during myelosuppression. Furthermore, our studies indicate that infused LTMC cells, at the above doses, can contribute to hematopoietic recovery, but are not essential for recovery following TBI, and do not shorten the period of prolonged profound myelosuppression induced by TBI.}, }
@article {pmid8446638, year = {1993}, author = {Stuchfield, B}, title = {An alternative to the colostomy. Electrically stimulated neoanal sphincter for the treatment of faecal incontinence.}, journal = {Professional nurse (London, England)}, volume = {8}, number = {6}, pages = {354-358}, pmid = {8446638}, issn = {0266-8130}, mesh = {Electric Stimulation/*methods ; Fecal Incontinence/nursing/surgery/*therapy ; Humans ; Muscles/transplantation ; }, abstract = {Faecal incontinence is a disabling disorder which profoundly undermines self-esteem. ESNS is a new operation which may be an alternative to colostomy. Good communication, knowledge and expertise are vital in caring for patients undergoing ESNS. All treatment options should be considered for patients with faecal incontinence.}, }
@article {pmid7483727, year = {1993}, author = {Doss, MO and Frank, M and Sieg, I}, title = {[Cholestatic erythrohepatic protoporphyria: porphyrin metabolism before and after liver transplantation].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {31 Suppl 2}, number = {}, pages = {85-89}, pmid = {7483727}, issn = {0044-2771}, mesh = {Adult ; Child, Preschool ; Cholestasis, Intrahepatic/genetics/*physiopathology/surgery ; Erythropoiesis/physiology ; Female ; Follow-Up Studies ; Humans ; Liver/physiopathology ; Liver Function Tests ; Liver Transplantation/*physiology ; Male ; Middle Aged ; Porphyria, Hepatoerythropoietic/genetics/*physiopathology/surgery ; Postoperative Complications/*physiopathology ; Protoporphyria, Erythropoietic ; Protoporphyrins/blood ; }, abstract = {The ferrochelatase deficiency in protoporphyria leads to accumulation of protoporphyrin in erythrocytes and liver. Consequences are protoporphyrinemia with photosensitivity and liver damage (fibrosis, cirrhosis) with cholestasis. The latter are unpredictable and can be observed in about 10% of the patients. Protoporphyrin, the physiological main component of hepatocellular porphyrins, has a hepatotoxic effect in the high-concentrated crystalline storage form. The obligatory hepatobiliary excretion of the lipophil, erythropoietic increased accumulating protoporphyrin in protoporphyria strains the excretory function of the liver. Its restriction is followed by an exzessive protoporphyrin accumulation, which leads to protoporphyrin-induced, progressive cholestatic cirrhosis, icterus, and aggravation of the extrahepatic protoporphyrinemic cutaneous manifestation. In case of hepatobiliary complications a coproporphyria of diagnostic relevance develops with inversion of isomers. Simultaneously, the fecal protoporphyrin excretion decreases. After liver transplantation hyperbilirubinemia, protoporphyrinemia and coproporphyrinuria significantly went down. A protoporphyrinemia of about 20% of preoperative values reflects the persisting hereditary enzyme defect and the continuity of the metabolic disease.}, }
@article {pmid8433416, year = {1993}, author = {Jaeger, A and Jehl, F and Flesch, F and Sauder, P and Kopferschmitt, J}, title = {Kinetics of amatoxins in human poisoning: therapeutic implications.}, journal = {Journal of toxicology. Clinical toxicology}, volume = {31}, number = {1}, pages = {63-80}, doi = {10.3109/15563659309000374}, pmid = {8433416}, issn = {0731-3810}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Amanita ; Amanitins/*blood/pharmacokinetics/urine ; Child ; Child, Preschool ; Chromatography, High Pressure Liquid ; Female ; Humans ; Liver Function Tests ; Liver Transplantation ; Male ; Metabolic Clearance Rate ; Middle Aged ; Mushroom Poisoning/mortality/*physiopathology/therapy ; Prognosis ; Time Factors ; Tissue Distribution ; }, abstract = {The kinetics of alpha and beta amanitin were studied in 45 patients intoxicated with Amanita Phalloides. The amatoxins were analyzed by high performance liquid chromatography in plasma (43 cases), urine (35 cases), gastroduodenal fluid (12 cases), feces (12 cases) and tissues (4 cases). All patients had gastrointestinal symptoms and 43 developed an acute hepatitis. Two patients underwent successful liver transplantation. Eight patients, of whom three were children, died. The detection of amatoxins in the biological fluids was time dependent. The first sample was obtained at an average of 37.9 h post ingestion in the patients with positive results and at 70.6 h in the samples without detectable amatoxins. Plasma amatoxins were detected in 11 cases at 8 to 190 ng/mL for alpha and between 23.5 to 162 ng/mL for beta. In 23 cases amatoxins were detected in urine with a mean excretion per hour of 32.18 micrograms for alpha and 80.15 micrograms for beta. In 10 patients the total amounts eliminated in the feces (time variable) ranged between 8.4 and 152 micrograms for alpha amanitin and between 4.2 and 6270 micrograms for beta amanitin. In three of four cases amatoxins were still present in the liver and the kidney after day 5. Amatoxins were usually detectable in plasma before 36 h but were present in the urine until day 4. The rapid clearance indicates that enhanced elimination of amatoxins requires early treatment. Clearance of circulating amatoxins by day 4 spares the transplanted liver.}, }
@article {pmid8416775, year = {1993}, author = {Pezim, ME and Johnson, HW and Gillespie, KD and Willard, P and Owen, DA}, title = {Creation of a pedicle valve unit (PVU) for establishment of enteric continence. Experimental observations.}, journal = {Diseases of the colon and rectum}, volume = {36}, number = {1}, pages = {16-22}, doi = {10.1007/BF02050296}, pmid = {8416775}, issn = {0012-3706}, mesh = {Anastomosis, Surgical/methods ; Animals ; Atrophy ; Cecum/pathology/physiology/*surgery ; Fecal Incontinence/pathology/physiopathology/*surgery ; Ileum/pathology/physiology/*transplantation ; Inflammation ; Intestinal Mucosa/pathology ; Pressure ; Rabbits ; Reoperation ; Transplantation, Autologous ; }, abstract = {The aim of this study was to develop a natural tissue valve that could be anastomosed into any area of the gastrointestinal (GI) tract to act as a fecal "brake" and so establish enteric continence at that site. A 4-cm-long valve created from an intussuscepted small bowel pedicle was anastomosed into the cecum and brought out through the abdominal wall as a stoma in 11 rabbits. The animals were re-explored five weeks later for assessment of valve viability and continence and microscopic appearance. In all cases, the valve was fully continent in vivo. All valves were viable, and there was no anastomotic leakage. Pressure testing of the valve at reoperation revealed that 7 of 10 valves tested withstood pressures of 30 mmHg before and after catheterization and 6 of 10 were fully continent to cecal "blanching" pressure (50 mmHg). Valve failure was due to deintussusception in three cases. In four cases, valves were continent over 50 mmHg and showed no tendency to incontinence to bursting pressure of the cecum. We conclude that a continent pedicle valve unit (PVU) for placement in a variety of locations in the GI tract is feasible. The PVU has implications in the management of short-gut syndrome, incontinent ileostomy, continent cecostomy, and as a continent valve placed in the perineum for restoration of perineal defecation following proctectomy.}, }
@article {pmid8412434, year = {1993}, author = {Schlemminger, R and Lottermoser, S and Sostmann, H and Köhler, H and Nustede, R and Schafmayer, A}, title = {[Metabolic parameters and neurotensin liberation after resection of the small intestine, syngeneic and allogeneic segment transplantation the rat].}, journal = {Langenbecks Archiv fur Chirurgie}, volume = {378}, number = {5}, pages = {265-272}, pmid = {8412434}, issn = {0023-8236}, mesh = {Animals ; Blood Glucose/metabolism ; Body Weight/physiology ; Energy Metabolism/physiology ; Feces/chemistry ; Intestinal Absorption/*physiology ; Intestine, Small/physiopathology/surgery/*transplantation ; Male ; Neurotensin/*metabolism ; Postoperative Complications/physiopathology ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; Short Bowel Syndrome/physiopathology/*surgery ; Transplantation, Homologous/physiology ; Transplantation, Isogeneic/physiology ; Triglycerides/blood ; }, abstract = {The aim of the following study was to gain some insight into the functional characteristics of different portions of the small intestine after either partial resection or syngeneic and allogeneic transplantation 3 months postoperatively. Nutritional parameters (serum albumin levels, serum triglyceride levels, maltose absorption, excretion of fecal fat) and fat-stimulated neurotensin release were determined in Lewis rats that underwent small-bowel resection (n = 21), syngeneic (Lewis-->Lewis, n = 21), or allogeneic transplantation (Brown Norway-->Lewis, n = 24). The length of the remnant, isograft, or allograft was 27 cm (i.e., one-third of the rat small intestine) and consisted of the proximal (n = 7), middle (n = 7), or distal (n = 7) portion. Three postoperative deaths were due to ileus or pneumonia. After allotransplantation cyclosporine (15 mg/kg body wt. s.c.) was administered for graft acceptance. The control group was not operated upon, but was composed of weight- and age-matched Lewis rats (n = 7). We found that resection of two-thirds of the small intestine led to significantly lower levels of albumin and triglycerides in all three portions investigated (P < 0.01), but did not affect maltose absorption. Excretion of fecal fat was elevated significantly only after distal resection (P < 0.05). When compared to resected animals, syngeneic transplantation did not affect the nutritional parameters, but caused a significantly higher hormone release (P < 0.05) in all three different intestinal grafts. Allogeneic transplantation was successful when the middle or distal portion was grafted. All recipients of proximal allografts showed a severe loss of body weight and died between day 8 and 10 after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid8365428, year = {1993}, author = {Borzi, P and Gough, DC}, title = {Pedicled gastric tube as a catheterising conduit.}, journal = {European urology}, volume = {24}, number = {1}, pages = {103-105}, doi = {10.1159/000474273}, pmid = {8365428}, issn = {0302-2838}, mesh = {Child ; Colon/*surgery ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Stomach/*transplantation ; *Surgical Flaps ; Urinary Bladder/*surgery ; Urinary Diversion/*methods ; Urinary Incontinence/*surgery ; }, abstract = {Treatment of urinary and faecal incontinence using the Mitrofanoff principle or the antegrade continence enema technique requires the creation of a catheterisable stoma. Although the appendix is by far the most satisfactory structure for the creation of this channel, its removal or use in previous surgical reconstruction may force the use of alternatives. We describe the use of the pedicled gastric tube for this purpose.}, }
@article {pmid8330692, year = {1993}, author = {Elias, D and Lasser, P and Leroux, A and Rougier, P and Comandella, MG and Deraco, M}, title = {[Pseudo-continent perineal colostomies after amputation of the rectum for cancer].}, journal = {Gastroenterologie clinique et biologique}, volume = {17}, number = {3}, pages = {181-186}, pmid = {8330692}, issn = {0399-8320}, mesh = {Adenocarcinoma/pathology/*surgery ; Adult ; Aged ; Carcinoma, Squamous Cell/*surgery ; Colostomy/*methods ; Fecal Incontinence/etiology ; Female ; Humans ; Liver Neoplasms/secondary ; Male ; Melanoma/surgery ; Middle Aged ; Neoplasm Recurrence, Local ; *Perineum ; Postoperative Complications ; Rectal Neoplasms/pathology/*surgery ; }, abstract = {From February 1989 to February 1982, 23 pseudocontinent perineal colostomies (PC), performed after abdominoperineal excision for rectal carcinoma, were evaluated. Perineal colostomy was performed using a free autotransplant of smooth muscle, according to Schmidt, associated with colonic irrigations. This procedure was proposed to the younger and more alert patients without advanced rectal carcinoma. These 23 cases represented 35% of the rectal extirpations performed during the same period. Four patients did not accept a PC and preferred, after being fully informed about both types of colostomies, to have a classical iliac colostomy which they thought to be safer. The advantages of this procedure were mainly psychological, as the body scheme and corporeal image were not disturbed. Continence was evaluated in only 21 cases, because two patients had non-specific complications (necrosis of the colonic extremity, and colonic perforation due to enema material). Ten patients were incontinent to flatus, but did not have to wear a sanitary towel, while 11 patients had occasional, minor soiling, requiring the use of a sanitary towel. None of the patients had major incontinence requiring a secondary iliac colostomy. When asked what they thought of results, none said that they were dissatisfied. The degree of satisfaction was subjective and was not correlated with the quality of functional results as seven patients declared themselves satisfied although they had minor soiling, and conversely, two patients were not completely satisfied, even though they had no soiling. Six months after operation, the muscular transplanted ring had disappeared in half of the patients, but this did not seem to have any repercussion of the quality of functional results.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid8292968, year = {1993}, author = {Siler, K and Eggensperger, D and Hand, PH and Milenic, DE and Miller, LS and Houchens, DP and Hinkle, G and Schlom, J}, title = {Therapeutic efficacy of a high-affinity anticarcinoembryonic antigen monoclonal antibody (COL-1).}, journal = {Biotechnology therapeutics}, volume = {4}, number = {3-4}, pages = {163-181}, pmid = {8292968}, issn = {0898-2848}, mesh = {Adenocarcinoma, Mucinous/pathology/radiotherapy ; Animals ; Antibodies, Monoclonal/administration &amp; dosage/*therapeutic use ; Carcinoembryonic Antigen/*immunology ; Colonic Neoplasms/pathology/*radiotherapy ; Female ; Humans ; Immunotoxins/administration &amp; dosage/*therapeutic use ; Iodine Radioisotopes/administration &amp; dosage/*therapeutic use ; Mice ; Mice, Nude ; Neoplasm Transplantation ; *Radioimmunotherapy ; Transplantation, Heterologous ; Tumor Cells, Cultured ; }, abstract = {COL-1 is a murine IgG2a monoclonal antibody (MAb) with a high affinity (1.4 x 10(9) M-1) for carcinoembryonic antigen (CEA) and no detectable reactivity for CEA-related antigens, such as nonspecific cross-reacting antigen (NCA) and normal fecal antigen (NFA). 125I-labeled COL-1 IgG was shown to efficiently and specifically target the LS-174T human colon carcinoma xenograft in athymic mice. Dose titration studies in this same model with 131I-labeled COL-1 demonstrated reduction of tumor growth rate when 300 microCi of the immunoconjugate was used (0.005 > p > 0.001). Administration of higher levels as a single dose led to increased toxicity. Dose fractionation experiments with 131I-COL-1 demonstrated the ability to administer much higher levels of the immunoconjugate with little or no toxicity, which resulted in a greater therapeutic efficacy. For example, three fractions of 200 microCi of 131I-COL-1 given at weekly intervals (for a total of 600 microCi) resulted in the substantial reduction (p < 0.0005) of the growth of established tumors in 100% (7/7) of mice, and in no evidence of tumor growth in 71% (5/7) of mice, at the end of the 63-day observation period. These results thus demonstrate the potential therapeutic efficacy for radiolabeled COL-1 in clinical trials and demonstrate the principle of the advantage of dose fractionation protocols for this immunoconjugate.}, }
@article {pmid8235074, year = {1993}, author = {Schlemminger, R and Lottermoser, S and Gieseler, RK and Sostmann, H and Nustede, R and Köhler, H and Schafmayer, A}, title = {The adaptive response of the rat small intestine after resection and segmental transplantation during the early postoperative phase.}, journal = {Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie}, volume = {193}, number = {4}, pages = {213-224}, doi = {10.1007/BF02576229}, pmid = {8235074}, issn = {0300-9130}, mesh = {*Adaptation, Physiological ; Animals ; Graft Rejection/prevention &amp; control ; Immunosuppression Therapy ; Intestine, Small/*physiology/surgery/*transplantation ; Male ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; Transplantation, Homologous ; Transplantation, Isogeneic ; }, abstract = {Organ harvesting from a living donor or spatial constraints in the recipient's abdominal cavity are the main factors to be considered in the segmental transplantation of the small intestine. It was the aim of the following study to gain insight into the functional characteristics of different portions of the small intestine either after partial resection or syngeneic and allogeneic transplantation during the early postoperative period. Nutritional parameters (serum albumin levels, serum triglyceride levels, maltose absorption, excretion of fecal fat) and fat-stimulated neurotensin release were determined in Lewis rats that underwent small bowel resection (n = 21), syngeneic (Lewis-->Lewis, n = 21), or allogeneic transplantation (Brown Norway-->Lewis, n = 24). The length of the remnant, isograft, or allograft was 27 cm (i.e. one third of the rat small intestine) and consisted of the proximal (n = 7), middle (n = 7), or distal (n = 7) portion. Three postoperative deaths were due to ileus or pneumonia. After allotransplantation, cyclosporine (15 mg/kg BW s.c.) was administered for graft acceptance. Controls were unoperated, weight- and age-matched Lewis rats (n = 7). We found that resection of two-thirds of the small intestine led to significantly lower levels of albumin and triglycerides in all the three portions investigated (P < 0.01) but did not affect maltose absorption. Excretion of fecal fat was elevated after distal resection (P < 0.05). When compared to resected animals, syngeneic transplantation did not affect the nutritional parameters, but caused a significantly higher hormone release (P < 0.05) in all three different intestinal grafts. Allogeneic transplantation was successful when the middle or distal portion was grafted. All recipients of proximal allografts showed a severe loss of body weight and died between day 8 and 10 after transplantation. Postmortem examination revealed no signs of acute rejection. When transplantation of short intestinal segments is considered, it is of vital importance to take into account the functional differences and the influence of immunosuppressive drug therapy in the regulatory bowel function.}, }
@article {pmid7689443, year = {1993}, author = {Korten, V and Murray, BE}, title = {Impact of the fluoroquinolones on gastrointestinal flora.}, journal = {Drugs}, volume = {45 Suppl 3}, number = {}, pages = {125-133}, pmid = {7689443}, issn = {0012-6667}, mesh = {Anti-Infective Agents/*pharmacology ; Bacteria, Anaerobic/drug effects ; Digestive System/*drug effects/*microbiology ; Drug Resistance, Microbial ; Feces/microbiology ; Fluoroquinolones ; Gram-Negative Bacteria/drug effects ; Gram-Positive Bacteria/drug effects ; Humans ; }, abstract = {A number of studies have been performed to evaluate the effect of the fluoroquinolones on gastrointestinal flora. The fluoroquinolones have only slight or no effect on the oropharyngeal flora, except when Neisseria, Haemophilus or Branhamella spp. are present. Studies have consistently shown that Gram-negative facultative bacteria of the lower intestinal flora are strongly suppressed during administration of these agents. Total faecal anaerobes are generally unchanged. The effect of the fluoroquinolones on Gram-positive bacteria is more variable with mild to moderate suppression reported with some agents. In view of the high faecal concentrations of the fluoroquinolones, the general lack of effect on anaerobes is surprising; it may be attributable to the large number of microorganisms found in faeces and faecal binding of the fluoroquinolones. Several recent studies suggest that the effects of some fluoroquinolones on faecal anaerobes and Gram-positive cocci may be more profound in certain patient populations such as bone marrow transplant recipients and patients undergoing gastrointestinal surgery. Colonisation with yeasts and the emergence of resistant bacterial strains have been reported during or after fluoroquinolone administration in some studies. Future studies will need to investigate the effect of the newer agents with greater activity against anaerobes and Gram-positive cocci on the gastrointestinal flora and to continue surveillance for resistant organisms.}, }
@article {pmid1480242, year = {1992}, author = {Rademaker, CM and Rozenberg-Arska, M and Fluit, AC and Wolfhagen, MJ and Glerum, JH and Verhoef, J}, title = {[Detection of diarrhea-causing Escherichia coli using DNA-probes].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {136}, number = {52}, pages = {2581-2584}, pmid = {1480242}, issn = {0028-2162}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; *DNA Probes ; Diarrhea/*microbiology ; Escherichia coli/classification/*isolation &amp; purification ; Feces/microbiology ; Humans ; Infant ; Middle Aged ; Netherlands ; Serotyping ; Spain ; Travel ; Tunisia ; }, abstract = {To assess the role of enterovirulent Escherichia coli at home and abroad, faeces samples of patients with diarrhoea and of healthy controls in Tunisia, Seville (southern Spain) and the Netherlands were investigated. Enterovirulent E. coli were identified by hybridization with five different non-radioactively labelled DNA probes specific for enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC) and verocytotoxin producing E. coli (VTEC). ETEC was the main causative agent of travellers' diarrhoea in Tunisia. The isolation of ETEC in the Netherlands was shown to be related to travel in endemic areas. EPEC probe positive strains were isolated in children and in adults, but were not in all cases associated with intestinal disease. During this study no VTEC were detected. From an immunocompromised kidney transplantation patient with sepsis and diarrhoea ETEC were isolated from blood.}, }
@article {pmid1460507, year = {1992}, author = {Tarburton, JP and Halpern, SE}, title = {Chromatofocusing studies involving a monoclonal Fab'.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {33}, number = {12}, pages = {2148-2153}, pmid = {1460507}, issn = {0161-5505}, mesh = {Animals ; *Antibodies, Monoclonal ; Colonic Neoplasms/diagnostic imaging ; Disease Models, Animal ; Electrophoresis ; Humans ; *Immunoglobulin Fab Fragments ; Iodine Radioisotopes ; Isoelectric Focusing ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Radioimmunodetection/*methods ; Transplantation, Heterologous ; }, abstract = {Isoelectric focusing (IEF) of the Fab' derivative of murine monoclonal antibody ZCE-025 is known to detect at least six bands having isoelectric points (pI) ranging from 5.4 to 7.8. Chromatofocusing was employed to separate these bands. Electrophoresis of the starting materials under nonreducing conditions indicated all of the materials to migrate as Fab'. The electrophoresis of urine samples obtained from Balb/c and nude mice 8 hr after the i.v. injection of the various 125I bands revealed the low pI bands to migrate approximately as a 125I-Fab'. The higher pI band activity was located in lower molecular weight regions. Serum samples taken at 8 hr postinjection from the above mice revealed a series of what appeared to be high molecular weight complexes and some low molecular weight species. Biodistribution studies in comparison Balb/c mice and nude mice revealed that the low pI 125I-Fab' bands gave an organ and tumor uptake at 8 hr very similar to Fab', while the high pI 125I-Fab' bands were rapidly excreted into the urine and feces and did not concentrate in the tumor. The data suggest that the population of molecules making up the Fab' of this antibody is heterogeneous and variably stable. Theoretically, some of the entities observed could be counter productive to successful radioimmunoimaging. It is also possible that some of the labeled molecules are associating in vivo with endogenous proteins that might, in some Mabs, affect the biodistribution of the radiopharmaceutical.}, }
@article {pmid1493152, year = {1992}, author = {Thunell, S and Henrichson, A and Floderus, Y and Groth, CG and Eriksson, BG and Barkholt, L and Nemeth, A and Strandvik, B and Eleborg, L and Holmberg, L}, title = {Liver transplantation in a boy with acute porphyria due to aminolaevulinate dehydratase deficiency.}, journal = {European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies}, volume = {30}, number = {10}, pages = {599-606}, doi = {10.1515/cclm.1992.30.10.599}, pmid = {1493152}, issn = {0939-4974}, mesh = {Acute Disease ; Child ; Erythrocytes/enzymology ; Feces/chemistry ; Humans ; Liver/physiology ; *Liver Transplantation ; Male ; Porphobilinogen Synthase/*deficiency ; Porphyrias, Hepatic/enzymology/metabolism/*surgery ; Porphyrins/blood/urine ; }, abstract = {The clinical and biochemical outcome of a liver transplantation in a seven-year-old boy with acute porphyria due to aminolaevulinate dehydratase deficiency is described. Before transplantation standard liver function tests were normal and the rationale for transplantation was that the new liver would reduce the metabolic disturbance and thus avert the porphyric symptoms. During the year after the transplantation, the functioning of the new liver has been excellent. Basal excretion of porphyrin and porphyrin precursors has remained unchanged but, with the new liver transplant the patient has been able to withstand several porphyrinogenic challenges without increasing the excretion. Episodes of neurological and respiratory crises may have been due to persistent porphyric vulnerability. Alternatively, two early attacks may have been caused by neurotoxic effects of cyclosporin in combination with the existing damage to nervous tissue.}, }
@article {pmid1461226, year = {1992}, author = {Vöhringer, HF and Arasteh, K and Link, H and Ehninger, G and Hardtmann, I}, title = {[Determinants of serum pentamidine concentration in the human].}, journal = {Medizinische Klinik (Munich, Germany : 1983)}, volume = {87 Suppl 1}, number = {}, pages = {24-29}, pmid = {1461226}, issn = {0723-5003}, mesh = {AIDS-Related Opportunistic Infections/*blood/drug therapy ; Administration, Inhalation ; *Bone Marrow Transplantation ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Humans ; Metabolic Clearance Rate/physiology ; Opportunistic Infections/*blood/drug therapy ; Pentamidine/administration &amp; dosage/*pharmacokinetics ; Pneumonia, Pneumocystis/*blood/drug therapy ; Prospective Studies ; }, abstract = {By means of serial measurements of pentamidine in plasma, urine and feces the significance of biologically available dose, volume of distribution, elimination and dose interval for serum concentration is investigated in patients with AIDS and bone marrow transplantation after inhaled and intravenous application. Aerosolisation of the drug yields to serum concentration mostly below the detection limit (HPLC). In urine only 0.15 to 0.8% of the substance biologically available in the lung are measured as unaltered pentamidine-base. After i.v. infusion the dose dependent low serum concentrations of 30 to 100 ng/ml indicate a fast distribution in peripheral compartments from which a very slow deliberation is seen. The half-life of the drug is also dose dependent and amounts under clinical conditions at minimum four days. The fecal excretion is found to be only one third of that measured in urine. A difference in the kinetic of elimination between bone marrow transplantated and AIDS-patients could not be evaluated. For clinical therapy the most important pharmacokinetic variable seems to be the terminal elimination constant which would implicate a prolongation of the common dose interval.}, }
@article {pmid1401996, year = {1992}, author = {Darmstadt, GL and Donnenberg, AD and Vogelsang, GB and Farmer, ER and Horn, TD}, title = {Clinical, laboratory, and histopathologic indicators of the development of progressive acute graft-versus-host disease.}, journal = {The Journal of investigative dermatology}, volume = {99}, number = {4}, pages = {397-402}, doi = {10.1111/1523-1747.ep12616112}, pmid = {1401996}, issn = {0022-202X}, support = {CA44887/CA/NCI NIH HHS/United States ; }, mesh = {Acute Disease ; Adolescent ; Adult ; Bilirubin/blood ; Biopsy ; Bone Marrow Transplantation/immunology ; Child ; Child, Preschool ; Cyclosporine/therapeutic use ; Feces/chemistry ; Graft vs Host Disease/*diagnosis ; Humans ; Middle Aged ; Skin/pathology ; Whole-Body Irradiation ; }, abstract = {Graft-versus-host disease (GvHD) is the major cause of morbidity and mortality following bone marrow transplantation (BMT). The goal of this study of 69 cyclosporin-treated, allogeneic BMT patients was to identify early clinical, laboratory, or histopathologic indicators of the development of progressive, fatal GvHD. Peak values within 100 d of allogeneic BMT for total bilirubin, stool volume in a day, clinical stage of cutaneous GvHD (based on extent of rash), and overall clinical stage of GvHD (based on a combination of graft-versus-host reactions in the skin, liver, and gastrointestinal tract) were most useful (p less than 0.05, by logistic regression) in identifying those patients with clinically progressive and fatal GvHD. Peak values for each of these parameters were reached an average of 40 d or less after BMT. Each unit increase in peak clinical stage of rash (e.g., stage 2 versus stage 3) was associated with an odds ratio incremental risk of 5.8 for clinical progression of GvHD, and each tenfold increase in peak total bilirubin (e.g., 2 mg/dl versus 20 mg/dl) or stool output in a day (e.g., 100 cm3/d versus 1000 cm3/d) was associated with an incremental risk of 8.4 and 10.6, respectively, for a fatal outcome from GvHD. Number of exocytosed lymphocytes and dyskeratotic epidermal keratinocytes (DEK) per linear millimeter of epidermis, the presence of follicular involvement, and the degree of dermal perivascular lymphocytic infiltration in 121 skin biopsy specimens were not associated with the development of progressive or fatal GvHD. Pretransplant total body irradiation was associated (p = 0.03, by Mann-Whitney U testing) with an increased number of DEK in skin biopsy specimens taken less than 20 d after BMT. This study demonstrates that monitoring of total bilirubin, stool output, extent of rash, and overall clinical stage of GvHD is most useful during the first 40 d after BMT in formulating the prognosis of early acute GvHD in allogeneic BMT patients receiving cyclosporin.}, }
@article {pmid1484154, year = {1992}, author = {Mion, FB and Faure, JL and Berger, F and McGregor, B and Perrot, H and Paliard, P}, title = {Liver transplantation for erythropoietic protoporphyria. Report of a new case with subsequent medium-term follow-up.}, journal = {Journal of hepatology}, volume = {16}, number = {1-2}, pages = {203-207}, doi = {10.1016/s0168-8278(05)80116-3}, pmid = {1484154}, issn = {0168-8278}, mesh = {Adult ; Dermatitis, Photoallergic/etiology ; Follow-Up Studies ; Humans ; Liver/metabolism ; *Liver Transplantation ; Male ; Porphyria, Hepatoerythropoietic/complications/metabolism/*surgery ; Protoporphyrins/biosynthesis ; Recurrence ; }, abstract = {We report a new case of successful liver transplantation in a 36-year-old patient with terminal hepatic failure due to erythropoietic protoporphyria. Data regarding protoporphyrin levels in erythrocytes and feces, before and after transplantation, seem to indicate that in this case protoporphyrin overproduction was in part due to liver synthesis. Four years after surgery, the patient is completely free of skin photosensitivity. His liver function tests are normal; there are no visible protoporphyrin deposits or ultrastructural abnormalities in his new liver. However, recurrence of the disease in the long term cannot be excluded, since erythrocyte protoporphyrin levels remained elevated after liver transplantation.}, }
@article {pmid1631494, year = {1992}, author = {de Bruin, RW and Heineman, E and Jeekel, J and Meijssen, MA and Lindemans, J and Bonthuis, F and Marquet, RL}, title = {Functional aspects of small-bowel transplantation in rats.}, journal = {Scandinavian journal of gastroenterology}, volume = {27}, number = {6}, pages = {483-488}, doi = {10.3109/00365529209000109}, pmid = {1631494}, issn = {0036-5521}, mesh = {Absorption ; Animals ; Blood Proteins/analysis ; Cyclosporine/administration &amp; dosage/pharmacokinetics ; Graft Survival ; Growth ; Intestine, Small/*transplantation ; Rats ; Rats, Inbred Strains ; Serum Albumin/analysis ; Transplantation, Isogeneic ; }, abstract = {Although clinical small-bowel transplantation is still severely hindered by rejection of the graft, prolonged graft survival can be achieved by using cyclosporin A in several experimental models of small-bowel transplantation. In an immunologically quiescent phase after transplantation, the important question arises whether a small-bowel allograft has enough functional capacity to maintain a normal nutritional status. We investigated the functional capacity of orthotopic small-bowel transplants and evaluated the ability of the total small-bowel transplant to absorb orally given cyclosporin in the early postoperative period and the effect of this oral cyclosporin treatment on allograft survival as compared with intramuscular administration. Between 3 and 7 months postoperatively, recipients of syngeneic and allogeneic total small-bowel transplants and syngeneic jejunal segmental grafts had significantly decreased serum triglyceride levels. Total serum protein and albumin concentrations, serum cholesterol values, fecal fat excretion, and percentage of split fatty acids were normal. One year after transplantation the weight in the groups transplanted with a total small-bowel graft was not different from age-matched untreated controls. Animals grafted with a segmental graft, however, showed a significantly impaired growth and had not reached a normal weight 1 year after transplantation. Growth was also significantly impaired after near-total small-bowel resection. These animals had to be killed because of their poor condition. Cyclosporin absorption after small-bowel transplantation equalled that in normal controls. Graft survival after intramuscular treatment, however, was significantly better than after oral treatment.}, }
@article {pmid1603163, year = {1992}, author = {van Leusen, R and Roldaan, B and Dennesen, PJ and Bosch, FH}, title = {[9-year experience with continuous ambulatory peritoneal dialysis in one center].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {136}, number = {22}, pages = {1068-1073}, pmid = {1603163}, issn = {0028-2162}, mesh = {Actuarial Analysis ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Peritoneal Dialysis, Continuous Ambulatory/adverse effects/mortality ; Peritonitis/etiology/microbiology ; Survival Analysis ; }, abstract = {The experience gained with CAPD in a group of 101 patients with terminal renal failure and a subgroup of 19 patients with diabetes mellitus was analysed. The actuarial patient survival was 81% after two years and 50% after five years. The combined patient-technique survival after two years was 48.8%. The most important reasons for drop-out were transplantation (25%) and death (24%). Death was method-related in 4 patients and caused by peritonitis in 2 of them. More often peritonitis was the cause of morbidity and temporary interruption (10 x) or of permanent abandoning of the method (11 x). The peritonitis frequency during the whole period of nine years was 1 : 11.3 months. Use of the Y-connector Twinbag system and a U.V.-light system reduced the incidence substantially. However, faecal peritonitis remains a dangerous situation which cannot be prevented in this way. The mortality in patients with diabetes mellitus is high but not method-related. The incidence of peritonitis is not significantly different from that among patients without diabetes mellitus.}, }
@article {pmid1629029, year = {1992}, author = {Vora, MM and Dhalla, M}, title = {In vivo studies of unlabeled and radioiodinated rhodamine-123.}, journal = {International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology}, volume = {19}, number = {3}, pages = {405-410}, doi = {10.1016/0883-2897(92)90126-j}, pmid = {1629029}, issn = {0883-2897}, mesh = {Animals ; Chromatography, High Pressure Liquid ; Female ; Iodine Radioisotopes/metabolism/*pharmacokinetics ; Mammary Neoplasms, Experimental/metabolism/pathology ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism ; Neoplasm Transplantation ; Rhodamine 123 ; Rhodamines/metabolism/*pharmacokinetics ; Tissue Distribution ; Tumor Cells, Cultured ; }, abstract = {Radioiodinated rhodamine-123 (Rh123), potential tumor imaging agent, was injected in mice bearing experimentally-induced tumors to investigate its tissue distribution. Some accumulation of radioactivity was found in tumors; most of it cleared rapidly from the blood after injection. Also, the radioiodinated Rh123 had metabolized to water-soluble species which was excreted in urine and feces. Unlabeled Rh123, on the other hand, accumulated only marginally in the tumors. However, it was found to accumulate significantly in the heart; as much as seventy times the level in blood at 4 h post-injection. Accumulation of unlabeled Rh123 increased steadily even at 24 h post-injection; whereas, it cleared rapidly from the blood via the kidney. This finding of selective accumulation of Rh123 in heart could be exploited in synthesizing 11C- and 18F-labeled Rh123 for use in PET studies of the myocardium.}, }
@article {pmid1537495, year = {1992}, author = {Schleiffenbaum, BE and Minder, EI and Möhr, P and Decurtins, M and Schaffner, A}, title = {Cytofluorometry as a diagnosis of protoporphyria.}, journal = {Gastroenterology}, volume = {102}, number = {3}, pages = {1044-1048}, doi = {10.1016/0016-5085(92)90195-5}, pmid = {1537495}, issn = {0016-5085}, mesh = {Adult ; Chromatography, High Pressure Liquid ; Erythrocytes/metabolism ; Feces/chemistry ; Female ; Flow Cytometry ; Humans ; Liver Diseases/*diagnosis ; Liver Transplantation ; Photosensitivity Disorders/diagnosis ; Porphyrias/*diagnosis ; Protoporphyrins/*analysis/urine ; }, abstract = {Protoporphyria is a disorder that usually has cutaneous symptoms. Only in a few cases liver disease develops, invariably progressing to cirrhosis and liver failure. A case of a patient who suffered from photosensitivity as a result of protoporphyria since the age of 2 is described. At age 33, she first presented with cholestatic hepatitis. At age 40, liver failure developed requiring liver transplantation. Quantitative cytofluorometry proved to be a quick and simple method in the follow-up of her erythrocyte protoporphyrin levels before, during, and after transplantation. Fluorescence correlated well with the protoporphyrin levels obtained by high-performance liquid chromatography (r = 0.98), a comparably cumbersome and complicated method for the determination of protoporphyrin. In addition, single cell analysis enabled us to follow the effects of transfusion therapy on protoporphyrin levels of the patient's own erythrocytes, which has not been possible by previous methods. Thus, cytofluorometry might prove to be elegant and useful for screening and future studies on therapy and pathophysiology of protoporphyria.}, }
@article {pmid1403068, year = {1992}, author = {Bosi, A and Fanci, R and Pecile, P and Guidi, S and Saccardi, R and Vannucchi, AM and Longo, G and Donnini, E and Orsi, A and Rossi-Ferrini, P}, title = {Aztreonam versus colistin-neomycin for selective decontamination of the digestive tract in patients undergoing bone marrow transplantation: a randomized study.}, journal = {Journal of chemotherapy (Florence, Italy)}, volume = {4}, number = {1}, pages = {30-34}, doi = {10.1080/1120009x.1992.11739135}, pmid = {1403068}, issn = {1120-009X}, mesh = {Aztreonam/*pharmacology ; *Bone Marrow Transplantation ; Colistin/*pharmacology ; Digestive System Diseases/*microbiology/prevention &amp; control ; Drug Therapy, Combination/pharmacology ; Feces/microbiology ; Fever ; Gram-Negative Bacterial Infections/*microbiology/prevention &amp; control ; Humans ; Immunocompromised Host ; Neomycin/*pharmacology ; Risk Factors ; Time Factors ; }, abstract = {Aztreonam (Az), a minimally absorbable monobactam antibiotic, was compared to colistin plus neomycin (CN), for intestinal decontamination during Bone Marrow Transplantation (BMT) in a controlled study. Thirty-four consecutive patients were randomized in two groups and evaluated for number of febrile episodes, days of fever, fecal cultures and clinical symptoms related to infections or colonizations. No significant differences were observed suggesting that Az is at least as effective as the CN regimen and may be considered as an alternative approach for intestinal decontamination in BMT patients.}, }
@article {pmid1728076, year = {1992}, author = {Thompson, JS and Rose, SG and Spanta, AD and Quigley, EM}, title = {The long-term effect of jejunoileal autotransplantation on intestinal function.}, journal = {Surgery}, volume = {111}, number = {1}, pages = {62-68}, pmid = {1728076}, issn = {0039-6060}, mesh = {Animals ; Dogs ; Ileum/*transplantation ; In Vitro Techniques ; Intestinal Absorption/*physiology ; Intestinal Mucosa/physiology ; Intestinal Secretions/microbiology ; Jejunum/*transplantation ; Nutritional Status ; }, abstract = {Disturbed intestinal absorption has been demonstrated almost uniformly early after intestinal autotransplantation. Our aim was to study the long-term effects of autotransplantation on intestinal absorptive function. Studies of nutritional status and absorptive function were performed on groups of dogs at three intervals after autotransplantation: I (less than 6 months; n = 4), II (6 to 12 months; n = 4), and III (12 to 18 months; n = 4). At death samples of intestinal fluid were obtained for bacteriologic analysis, and studies of morphology and in vitro absorption were performed on intact and autotransplanted intestine. Similar studies were performed on a group of five control animals. Although body weight and serum albumin levels remained stable in dogs that had undergone autotransplantation and initial diarrhea improved, stool moisture was persistently elevated and late defects in fat and D-xylose absorption developed (4.8% +/- 3.2% stool fat at 12 months vs 2.1% +/- 0.6% before surgery and 3.4 +/- 2.0 x 10(-2) mmol/L xylose/hr at 12 months vs 8.8 +/- 5.4 x 10(-2) mmol/L xylose/hr before surgery; p less than 0.05). In vitro glucose uptake and villus height were similar in autotransplanted and adjacent intact intestine at death. Compared with control animals, animals that had undergone autotransplantation demonstrated significant overgrowth of fecal flora in jejunum and ileum (14/18 segments greater than 10(5) bacteria vs 6/15 segments; p less than 0.05). Thus delayed defects in intestinal absorption of fat and D-xylose occurred more than 12 months after autotransplantation. Because intestinal structure and function of the autotransplanted intestine were similar to those of adjacent intact intestine, this malabsorption may be related to bacterial overgrowth or other in vivo factors.}, }
@article {pmid1727887, year = {1992}, author = {Michaels, MG and Green, M and Wald, ER and Starzl, TE}, title = {Adenovirus infection in pediatric liver transplant recipients.}, journal = {The Journal of infectious diseases}, volume = {165}, number = {1}, pages = {170-174}, pmid = {1727887}, issn = {0022-1899}, support = {R01 DK029961-19/DK/NIDDK NIH HHS/United States ; }, mesh = {Adenovirus Infections, Human/epidemiology/*etiology ; Adenoviruses, Human/isolation &amp; purification ; Adolescent ; Child ; Child, Preschool ; Cross Infection/epidemiology/*etiology ; Feces/microbiology ; Female ; Hepatitis, Viral, Human/epidemiology/etiology ; Humans ; Incidence ; Infant ; *Liver Transplantation ; Male ; Pennsylvania/epidemiology ; Pneumonia, Viral/epidemiology/etiology ; Respiratory System/microbiology ; Retrospective Studies ; Urine/microbiology ; }, abstract = {A retrospective review of adenoviral infection in pediatric liver transplant recipients was done at Children's Hospital of Pittsburgh to define its epidemiology and clinical importance. Medical records of patients with adenovirus were reviewed and data collected regarding clinical course, microbiologic studies, biopsy results, immunosuppression, concurrent infections, and outcome. Of 484 liver transplant recipients, 49 had 53 episodes of adenoviral infection. The most common sites of adenoviral infection were the liver, lung, and gastrointestinal tract. Serotypes 1, 2, and 5 were recovered most often; type 5 was commonly associated with hepatitis. Invasive adenoviral infection occurred in 20 children, leading to death in 9. Median time from transplantation until isolation of adenovirus was 25.5 days. This timing suggests either reactivation or donor-associated transmission. Prospective studies using molecular epidemiologic techniques will be helpful in evaluating transmission patterns of adenovirus in this population.}, }
@article {pmid1564856, year = {1992}, author = {Tat'ianchenko, VK}, title = {[A method of creating the sphincter apparatus of the rectum].}, journal = {Klinicheskaia khirurgiia}, volume = {}, number = {1}, pages = {19-21}, pmid = {1564856}, mesh = {Adolescent ; Adult ; Animals ; Child ; Child, Preschool ; Colostomy/*methods ; Disease Models, Animal ; Dogs ; Exercise Therapy ; Fecal Incontinence/physiopathology/rehabilitation/*surgery ; Graft Survival/physiology ; Humans ; Muscles/physiopathology/*transplantation ; Postoperative Care ; Preoperative Care ; *Surgical Flaps ; Thigh ; }, abstract = {The data on surgical anatomy of the musculus gracilis, which is used for sphincteroplasty, is presented. In the experiment on 25 dogs with modelled incompetence of the anal sphincter, a technique for cutting the non-free flaps out of the musculus gracilis and creation of obturator apparatus of the rectum has been developed. The advantages of a developed method over the existing ones, efficacy and possibility for its use in the clinic are shown.}, }
@article {pmid1413301, year = {1992}, author = {Allerberger, FJ and Dierich, MP and Ebner, A and Keating, MR and Steckelberg, JM and Yu, PK and Anhalt, JP}, title = {Urinary tract infection caused by nontyphoidal Salmonella: report of 30 cases.}, journal = {Urologia internationalis}, volume = {48}, number = {4}, pages = {395-400}, doi = {10.1159/000282362}, pmid = {1413301}, issn = {0042-1138}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Salmonella Infections/*complications/microbiology/urine ; Urinalysis ; Urinary Tract Infections/*etiology/microbiology/urine ; Urine/microbiology ; }, abstract = {Thirty cases of nontyphoidal Salmonella bacteriuria were identified by review of cultures performed at the Mayo Clinic (Minn.) from 1985 to 1989 and at the Federal Public Health Laboratory Innsbruck (Austria) from 1979 to 1989. All patients had symptoms of an acute urinary tract infection (UTI). In 24 cases nontyphoidal Salmonella was the sole pathogen isolated. Only 1 patient presented with concomitant gastroenteritis and 2 had experienced episodes of diarrhea during the weeks before the UTI, but 15 patients had positive stool cultures in the absence of a gastrointestinal illness. Among all positive urine cultures at the Mayo Microbiology Laboratory, 0.015% were positive for nontyphoidal Salmonella; at the Federal Public Health Laboratory Innsbruck, 0.024% of organisms cultured from urine were nontyphoidal salmonellae. In the majority of our patients, Salmonella UTI did not differ clinically from UTI caused by other members of the Enterobacteriaceae; only in renal transplant recipients was the course of genitourinary salmonellosis more serious. While some urinary isolates of nontyphoidal Salmonella may be fecal contaminants, all 30 isolates recovered from urine during this study were considered to be the cause of symptomatic UTI.}, }
@article {pmid1341282, year = {1992}, author = {Christiansen, J}, title = {Advances in the surgical management of anal incontinence.}, journal = {Chirurgie; memoires de l'Academie de chirurgie}, volume = {118}, number = {5}, pages = {277-82; discussion 282-3}, pmid = {1341282}, issn = {0001-4001}, mesh = {Adult ; Anal Canal/*surgery ; Fecal Incontinence/etiology/*surgery ; Female ; Humans ; Male ; Meningomyelocele/complications ; Muscles/transplantation ; Obstetric Labor Complications ; Pregnancy ; Prostheses and Implants ; Thigh ; }, abstract = {Standard procedures for anal incontinence due to trauma (obstetric lesions, iatrogenic lesions in connection with anal surgery) have been overlapping suture of the external anal sphincter and, for idiopathic incontinence, postnatal repair according to Parks. In cases where these operations fail, or if a pronounced sphincter destruction is found, transposition of striated muscles (primarily the gracilis and the gluteus maximus) may be performed. In patients where the incontinence is due to a primary neurological disease, implantation of an artificial sphincter or a neurostimulator may be the only alternatives. The technique and the results of these newer operations for anal incontinence are presented.}, }
@article {pmid1328948, year = {1992}, author = {Greaves, I and Kane, K and Richards, NT and Elliott, TS and Adu, D and Michael, J}, title = {Pigeons and peritonitis?.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {7}, number = {9}, pages = {967-969}, doi = {10.1093/ndt/7.9.967}, pmid = {1328948}, issn = {0931-0509}, mesh = {Adult ; Aged ; Animals ; Candida/*isolation &amp; purification ; Candidiasis/epidemiology/*etiology/therapy ; Columbidae/*microbiology ; Disease Outbreaks ; *Disease Vectors ; Female ; Humans ; Male ; Middle Aged ; Peritoneal Dialysis, Continuous Ambulatory/*adverse effects ; Peritonitis/epidemiology/*etiology/therapy ; }, abstract = {We report an outbreak of fungal peritonitis due to Candida parapsilosis in 12 patients undergoing chronic ambulatory peritoneal dialysis (CAPD). All 12 patients were treated by removal of the CAPD catheter together with systemic antifungal therapy. There were no peritonitis-related deaths. Four patients were successfully returned to CAPD at a later date. Microbiological investigation during the outbreak demonstrated colonization of various areas of the CAPD Unit and medical ward with the organism. C. parapsilosis was also isolated from pigeon guano obtained from window-sills. The number of cases of peritonitis due to this organism decreased markedly after bird-proof netting was installed. We believe that this is the first report of an outbreak of CAPD peritonitis due to faecal carriage of C. parapsilosis by pigeons.}, }
@article {pmid1777490, year = {1991}, author = {Hakelius, L and Olsen, L}, title = {Free autogenous muscle transplantation in children. Long-term results.}, journal = {European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie}, volume = {1}, number = {6}, pages = {353-357}, doi = {10.1055/s-2008-1042519}, pmid = {1777490}, issn = {0939-7248}, mesh = {Adolescent ; Child ; Fecal Incontinence/*surgery ; Female ; Follow-Up Studies ; Humans ; Humerus ; Male ; Muscles/*transplantation ; Patient Satisfaction ; Transplantation, Autologous ; }, abstract = {For more than 15 years we have been using free muscle transplantation in the treatment of anal incontinence in children. This method implies transposition of a striated muscle, usually the palmaris longus, two weeks after denervation, to the perirectal area as a U-sling around the rectum corresponding to the location of the so-called puborectalis muscle. We have now evaluated the long-term results in all 26 children operated on by this method. Before the operation all children were totally incontinent after a primary repair. At follow-up after an average of 11 years and 4 months, 60% of the cases were regarded as good, 16% as fair, 8% as improved and 16% as failures. In our opinion, free muscle transplantation offers a good chance of achieving acceptable continence in a majority of incontinent children.}, }
@article {pmid1773637, year = {1991}, author = {Lechner, P}, title = {[The mucosal sliding flap in the treatment of supra and high trans-sphincteric anal fistula].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {62}, number = {12}, pages = {891-894}, pmid = {1773637}, issn = {0009-4722}, mesh = {Adult ; Anal Canal/*surgery ; Colorectal Surgery/methods ; Female ; Follow-Up Studies ; Humans ; Intestinal Mucosa/*transplantation ; Male ; Rectal Fistula/*surgery ; *Surgical Flaps ; }, abstract = {Since 1989 we have operated upon 28 patients for trans- or suprasphincteric fistula, using the mucosal sliding flap: After injection of a vasoconstrictory agent into the submucosal tissue we sparingly excise the inner opening of the fistula just beyond the dentate line. A mucosal flap is then meticulously dissected and used to cover the lesion in the rectum. The flap prevents fecal bacteria from invading the intrasphincteric portion of the fistula. This portion remains intact, and so does the sphincter apparatus. Then we excise the fistulous tract, proceeding from its external opening towards the sphincter muscle. After a mean follow-up of 8.1 months all 28 patients are free of symptoms. Proctoscopy did not reveal persistent or recurrent fistula in any of them.}, }
@article {pmid1725271, year = {1991}, author = {Fichtner, I and Arndt, D and Reszka, R and Gens, J}, title = {Pharmacokinetic behavior of [57Co]bleomycin liposomes in mice: comparison with the unencapsulated substance.}, journal = {Anti-cancer drugs}, volume = {2}, number = {6}, pages = {555-563}, doi = {10.1097/00001813-199112000-00006}, pmid = {1725271}, issn = {0959-4973}, mesh = {Animals ; Bleomycin/*administration &amp; dosage/blood/pharmacology ; Cobalt ; Drug Carriers ; Female ; Leukemia P388/drug therapy/metabolism ; Liposomes ; Lymphoma, Large B-Cell, Diffuse/drug therapy/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Tissue Distribution ; }, abstract = {The distribution and excretion of [57Co]Bleomycin, dissolved in saline or encapsulated in liposomes, was studied in normal or tumor-bearing [P388 leukemia, reticulum cell sarcoma (RS)] mice. The free substance is cleared relatively quickly from the organism both after intravenous and intraperitoneal administration (t1/2 0.17 and 2.41 h, respectively), and is excreted predominantly via the urinary tract. In contrast, following entrapment in small unilamellar vesicles (SUV) or multilamellar vesicles (MLV), the 57Co radioactivity remains 7- to 30-fold longer in the blood stream and is detectable in considerable amounts in liver, spleen, lung and tumor of the RS model even after 48 h. Concomitantly, the renal excretion is diminished to about 50% of the free drug and the feces excretion is slightly increased, possibly due to the higher concentrations in the liver. Whereas the renal levels of radioactivity were similar with all application forms of [57Co]Bleomycin, there were marked differences in all the other tissues studied. After administration of SUV there was a higher activity in liver, brain and tumor, whereas MLV were more concentrated in spleen and lung. Therapeutic experiments confirmed the favorable results obtained with liposomes. While the free Bleomycin in the P388 leukemia had only a moderate influence on the lifetime of the animals with a treated/control value of 111%, encapsulation of the drug in SUV or MLV improved the results to 194 and 167%, respectively. In the intramuscular transplanted RS model, the SUV in a day 1 schedule had the same effect on tumor growth as the free drug in a day 1-4 schedule.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid1721268, year = {1991}, author = {Iwasaki, K and Shiraga, T and Nagase, K and Hirano, K and Nozaki, K and Noda, K}, title = {Pharmacokinetic study of FK 506 in the rat.}, journal = {Transplantation proceedings}, volume = {23}, number = {6}, pages = {2757-2759}, pmid = {1721268}, issn = {0041-1345}, mesh = {Administration, Oral ; Animals ; Bile/chemistry/metabolism ; Feces/chemistry ; Immunoenzyme Techniques ; Intestinal Absorption ; Male ; Microsomes, Liver/metabolism ; Rats ; Rats, Inbred Strains ; Tacrolimus/administration &amp; dosage/blood/*pharmacokinetics ; }, }
@article {pmid1682591, year = {1991}, author = {Williams, NS and Patel, J and George, BD and Hallan, RI and Watkins, ES}, title = {Development of an electrically stimulated neoanal sphincter.}, journal = {Lancet (London, England)}, volume = {338}, number = {8776}, pages = {1166-1169}, doi = {10.1016/0140-6736(91)92031-v}, pmid = {1682591}, issn = {0140-6736}, mesh = {Adolescent ; Adult ; Aged ; Algorithms ; Anal Canal/physiopathology/*surgery ; Combined Modality Therapy ; Electric Stimulation Therapy/*instrumentation/methods ; Electrodes, Implanted ; Equipment Design ; Evaluation Studies as Topic ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle Contraction/physiology ; Muscles/physiopathology/*transplantation ; }, abstract = {In early surgical attempts to create a neoanal sphincter for patients who are faecally incontinent, skeletal muscle (usually the gracilis) has been transposed around the anal canal. Despite modifications, such as intermittent electrical stimulation, this procedure is likely to fail because the fast-twitch gracilis muscle is incapable of prolonged contraction without fatigue. Long-term electrical stimulation to convert such a muscle to a slow-twitch, fatigue-resistant muscle, though practicable, has yielded inconsistent results. We describe further modifications of this technique. A neoanal sphincter was constructed with an electrically stimulated transposed gracilis muscle in 20 incontinent patients with a deficient anal sphincter, and as part of a reconstruction in 12 patients in whom the anorectum had been excised or was congenitally absent. A totally implanted stimulator was used to convert the muscle from a fast-twitch to a slow-twitch muscle. Other modifications included vascular delay 4-6 weeks before transposition of the muscle, stimulation of the main nerve to the gracilis rather than its peripheral branches, and intermittent higher frequency stimulation. 2-4 of these modifications gave significantly fewer failures than did 0-1. With the new technique, continence has been restored in patients whose only other treatment option was a permanent stoma.}, }
@article {pmid1682590, year = {1991}, author = {Baeten, CG and Konsten, J and Spaans, F and Visser, R and Habets, AM and Bourgeois, IM and Wagenmakers, AJ and Soeters, PB}, title = {Dynamic graciloplasty for treatment of faecal incontinence.}, journal = {Lancet (London, England)}, volume = {338}, number = {8776}, pages = {1163-1165}, doi = {10.1016/0140-6736(91)92030-6}, pmid = {1682590}, issn = {0140-6736}, mesh = {Adult ; Aged ; Anal Canal/physiopathology/*surgery ; Combined Modality Therapy ; Electric Stimulation Therapy/*methods ; Electrodes, Implanted ; Electromyography ; Evaluation Studies as Topic ; Fecal Incontinence/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Middle Aged ; Muscle Contraction/physiology ; Muscles/physiopathology/*transplantation ; }, abstract = {Serious faecal incontinence due to anal sphincter damage should be treated by surgery. Graciloplasty has had limited success because the gracilis is a fast-twitch muscle and fatigues quickly. A favourable outcome in a patient who had dynamic (electrically stimulated) graciloplasty encouraged us to further assess this procedure. Gracilis muscle transposition was done in ten patients with complete anal incontinence due to anal atresia, sphincter damage, or neurogenic causes, and who had had several other unsuccessful treatments. 6 weeks after muscle transposition, intramuscular leads were implanted and connected to an implantable electric stimulator. Eight patients became continent, one patient still has a diverting colostomy, and a fistula developed in the other patient. Anal sphincter pressure improved from 35 mm Hg without stimulation to 62 mm Hg with stimulation at 8 weeks (mean increase 28 mm Hg [95% confidence interval 18, 36], p less than 0.01). Retention time of a phosphate enema increased from 22 to 281 s (mean increase 259 s [82, 436], p less than 0.01). Defaecography showed that the new sphincter was functioning. Defaecation was possible when the stimulator was turned "off" with a magnet. Dynamic graciloplasty can restore continence and it improves quality of life in faecally incontinent patients for whom other treatments have been unsuccessful.}, }
@article {pmid1774255, year = {1991}, author = {Green, M and Barbadora, K and Michaels, M}, title = {Recovery of vancomycin-resistant gram-positive cocci from pediatric liver transplant recipients.}, journal = {Journal of clinical microbiology}, volume = {29}, number = {11}, pages = {2503-2506}, pmid = {1774255}, issn = {0095-1137}, support = {RR00084/RR/NCRR NIH HHS/United States ; }, mesh = {Adolescent ; Bacteremia/etiology/microbiology ; Child ; Child, Preschool ; Drug Resistance, Microbial ; Enterococcus/drug effects/isolation &amp; purification ; Feces/microbiology ; Gram-Positive Bacterial Infections/*etiology/microbiology ; Gram-Positive Cocci/*drug effects/*isolation &amp; purification ; Humans ; Infant ; Liver Transplantation/*adverse effects ; Time Factors ; Vancomycin/*pharmacology ; }, abstract = {Between November 1988 and October 1989, 49 first-time pediatric liver transplant recipients at the Children's Hospital of Pittsburgh were prospectively monitored for the presence of stool colonization and the development of disease caused by vancomycin-resistant gram-positive cocci (VRGPC). Quantitative stool culturing was done on a weekly basis, and cultures were planted onto a selective medium for VRGPC. Isolates for which the MIC was greater than or equal to 8 were considered resistant to vancomycin. Patients were monitored clinically for the development of infection, and their charts were systematically reviewed for the use of antibiotics. Eighty-six isolates were recovered from 36 of the 49 patients. Enterococcal species were isolated from 31 patients and included Enterococcus gallinarum (n = 28), E. casseliflavus (n = 14), E. faecium (n = 9), E. faecalis (n = 2), E. mundtii (n = 2), and E. durans (n = 1). Stool colonization with vancomycin-resistant enterococci was noted to increase steadily during the first month after transplantation. Only 9 of 31 patients demonstrated clearance of these organisms in serial repeat cultures. Additional isolates of VRGPC included Lactobacillus confusus (n = 13), Lactobacillus spp. (n = 12), and Pediococcus pentosaceus (n = 4). Infection due to VRGPC developed in three patients: a urinary tract infection in two and peritonitis in one. E. faecium was the pathogen in each of these cases. The ranges of MICs of vancomycin were 8 to 32 micrograms/ml for all enterococcal isolates and greater than 128 micrograms/ml for Lactobacillus and Pediococcus isolates. All Lactobacillus and Pediococcus isolates were resistant to teicoplanin, although they were susceptible to daptomycin. All other isolates were susceptible to both teicoplanin and daptomycin. This study demonstrates that stool colonization with VRGPC may be a common and early finding among pediatric liver transplant recipients. However, infection appears to be uncommon.}, }
@article {pmid1952998, year = {1991}, author = {Hussein, M and Howard, ER and Mieli-Vergani, G and Mowat, AP}, title = {Jaundice at 14 days of age: exclude biliary atresia.}, journal = {Archives of disease in childhood}, volume = {66}, number = {10}, pages = {1177-1179}, pmid = {1952998}, issn = {1468-2044}, mesh = {Age Factors ; Biliary Atresia/complications/diagnosis/*surgery ; Bilirubin/urine ; Feces/chemistry ; Humans ; Infant ; Infant Care ; Infant, Newborn ; Jaundice, Neonatal/*etiology ; Liver Transplantation ; Portoenterostomy, Hepatic ; Referral and Consultation ; }, }
@article {pmid1914720, year = {1991}, author = {Centeno Neto, AA and Veyrac, M and Briand, D and Spiliotis, J and Saint-Aubert, B and Joyeux, H}, title = {Autotransplantation of the pylorus sphincter at the terminal abdominal colostomy. Experimental study in dogs.}, journal = {Diseases of the colon and rectum}, volume = {34}, number = {10}, pages = {874-879}, doi = {10.1007/BF02049700}, pmid = {1914720}, issn = {0012-3706}, mesh = {Animals ; Colon/diagnostic imaging/pathology/physiology ; Colostomy/*methods ; Defecation ; Dogs ; Manometry ; Pressure ; Pylorus/blood supply/pathology/*transplantation ; Radiography ; Transplantation, Autologous ; }, abstract = {A method for constructing a continent colostomy has been tried in dogs. The pylorus sphincter with blood supply by the left gastroepiploic vessels was transposed around or anastomosed to the terminal abdominal colostomy in five dogs. One dog had a colostomy without pylorus transplantation. Evaluation was by clinical (consistency and weight of fecal material and number of defecations per day), radiologic, and manometry studies. There was no difference in the clinical data. In all the dogs, the radiologic study demonstrated emptying of the contrast medium to the peristomal skin. By manometry one high-pressure zone was demonstrated, and, in all dogs with a transposed or anastomosed pyloric segment, the average resting pressure was superior to that of the control dog. However, the transposed pylorus sphincter alone was not sufficient to control continence.}, }
@article {pmid1779332, year = {1991}, author = {Sonnino, RE and Reinberg, O and Bensoussan, AL and Laberge, JM and Blanchard, H}, title = {Gracilis muscle transposition for anal incontinence in children: long-term follow-up.}, journal = {Journal of pediatric surgery}, volume = {26}, number = {10}, pages = {1219-1223}, doi = {10.1016/0022-3468(91)90338-t}, pmid = {1779332}, issn = {0022-3468}, mesh = {Adolescent ; Adult ; Age Factors ; Anal Canal/physiology/*surgery ; Anus, Imperforate/complications/surgery ; Child ; Fecal Incontinence/etiology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Meningomyelocele/complications ; Muscles/*transplantation ; Postoperative Complications ; Rectum/physiology ; Surgical Procedures, Operative/methods ; *Thigh ; Time Factors ; Wounds and Injuries/complications ; }, abstract = {We report a series of 7 patients, aged 6.5 to 19 years (mean, 12.9), who have been treated for uncontrollable fecal incontinence since 1976: 5 had imperforate anus and multiple subsequent operative procedures, 1 had a low myelomeningocele with bi-sphincteric incontinence, and 1 had a traumatic destruction of the sphincter apparatus. A modified Pickrell procedure was performed, with the gracilis muscle transposed subcutaneously, without constructing a pulley through the median raphe as originally described. All patients were evaluated by anorectal manometry preoperatively and post-operatively. They were followed-up for a period of 0.5 to 12.5 years (mean, 4.4). All patients were continent at follow-up, with a normal defecation pattern and no enemas required. None of the patients had evidence of fibrosis of the muscle or anal canal, and tension in the transposed muscle was maintained. Voluntary contractions remain efficient in all cases. Age was thought to be an important factor: personal motivation and compliance with physiotherapy, essential for a good outcome, is unlikely to be present in the younger child. We conclude that the gracilis sling procedure is an excellent long-term alternative for total fecal incontinence when time and other therapeutic measures have failed.}, }
@article {pmid1887944, year = {1991}, author = {Adler, RA and Krieg, RJ}, title = {Normal food intake and growth in hyperprolactinemic rats.}, journal = {The American journal of physiology}, volume = {261}, number = {3 Pt 2}, pages = {R548-52}, doi = {10.1152/ajpregu.1991.261.3.R548}, pmid = {1887944}, issn = {0002-9513}, mesh = {Animals ; Body Weight ; Estradiol/pharmacology ; Feces ; *Feeding Behavior/drug effects ; Female ; Growth/*physiology ; Hyperprolactinemia/*physiopathology ; Hypophysectomy ; Muscles/transplantation ; Ovariectomy ; Pituitary Gland, Anterior/*physiology ; Prolactin/blood ; Rats ; Rats, Inbred F344 ; Transplantation, Heterotopic ; Weight Gain ; }, abstract = {Normal lactation, a state of chronic hyperprolactinemia, is often accompanied by increased food intake. Two recent reports suggested that, in rats, prolactin (PRL) administration or chronic endogenous PRL excess led to increased food intake and growth. Similar methods of achieving augmented circulating levels of PRL in rats have been employed in our laboratory. Rats with extra anterior pituitary (AP) grafts under the kidney capsule have chronically elevated circulating PRL levels. However, in several experiments, weight gain, food intake, and fecal weight were the same in AP-grafted rats and in control muscle-grafted rats. In addition, the AP-grafted rat model was modified to demonstrate that PRL-induced increases in adrenal glucocorticoids and decreases in estrogens did not provoke alterations in eating behavior. Injection of homologous PRL for 8 days did not increase weight gain in normal or hypophysectomized rats. These data suggest that neither the chronic PRL excess caused by AP grafts nor the acute PRL excess caused by rat PRL injections increases food intake or weight gain.}, }
@article {pmid1941487, year = {1991}, author = {Kitagawa, H and Ford, EG and Sinatra, F and Thomas, D and Atkinson, JB}, title = {Fecal fat, cyclosporine, and alpha 1-antitrypsin for assessment of small bowel function following transplantation.}, journal = {Journal of pediatric surgery}, volume = {26}, number = {9}, pages = {1091-5; discussion 1095-6}, doi = {10.1016/0022-3468(91)90680-r}, pmid = {1941487}, issn = {0022-3468}, mesh = {Animals ; Cyclosporine/*pharmacokinetics ; Dietary Fats/administration &amp; dosage ; Fats/*analysis ; Feces/*chemistry ; Intestinal Absorption ; Intestine, Small/*transplantation ; Male ; Maltose/pharmacokinetics ; Rats ; Rats, Inbred Lew ; alpha 1-Antitrypsin/*analysis ; }, abstract = {Many factors affect the integrity of transplanted small bowel. These include ischemic preservation and immunologic injury as well as the division of intestinal lymphatics during transplantation. This study was undertaken to evaluate the recovery of fat absorption in transplanted small bowel in syngeneic rats. Orthotopic transplantation of the total small bowel with resection of the native intestine was performed. The experimental (n = 11) and a pair-fed, sham-operated control (n = 8) groups were fed a 50% kcal corn oil semipurified diet. Studies of cyclosporine (CSA) absorption, maltose absorption, dietary fat, and fecal alpha 1-antitrypsin (FA1AT) excretion in transplanted animals were performed preoperatively and at 15, 30, and 50 days postoperatively. There was no significant difference in the weight change or fat and maltose absorption in experimental animals compared with control animals at any time point. Peak serum CSA levels were lower at day 15 in transplanted animals than in controls (P = 0.006) and improved but remained lower than those in controls at days 30 and 50 (P = 0.017). FA1AT excretion was increased on postoperative day 15 (accompanied by a decrease in body weight) and returned to control levels at days 30 and 50. Transplanted isogeneic rats had weight recovery and fat and carbohydrate absorption similar to those of controls. Transplanted animals had a protein-losing enteropathy measured by FA1AT at day 15 that resolved by 30 and 50 days, respectively. CSA absorption showed a much more gradual return to control levels and remained abnormal at 50 days.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid1881137, year = {1991}, author = {Sarr, MG and Duenes, JA and Walters, AM}, title = {Jejunal and ileal absorptive function after a model of canine jejunoileal autotransplantation.}, journal = {The Journal of surgical research}, volume = {51}, number = {3}, pages = {233-239}, doi = {10.1016/0022-4804(91)90100-z}, pmid = {1881137}, issn = {0022-4804}, support = {R01 DK39337/DK/NIDDK NIH HHS/United States ; }, mesh = {Absorption ; Animals ; Dietary Fats/pharmacokinetics ; Dogs ; Folic Acid/pharmacokinetics ; Ileum/metabolism/*transplantation ; Jejunum/metabolism/*transplantation ; Time Factors ; Transplantation, Autologous ; Vitamin B 12/pharmacokinetics ; Xylose/pharmacokinetics ; }, abstract = {The effects of intestinal transplantation on the physiologic functions of the gut are not well understood. Our aim was to determine the effect of a large animal model of small intestinal transplantation (disruption of all neural and lymphatic continuity) on selected absorptive functions of the jejunoileum. Seven dogs were studied before and at 1, 4, and 12 weeks after a model of jejunoileal autotransplantation, which avoids confounding factors of immune rejection, immunosuppression, and harvest ischemia. Jejunal function was assessed by quantitative [3H]-folate and D-xylose absorption and ileal function by quantitative 57Co-vitamin B12 absorption. The role of lymphatic continuity was assessed by fecal fat recovery following 5 days of a controlled, high fat diet (75 g/day). All dogs developed a profuse, watery diarrhea that persisted for 6 to 12 weeks and lost about 15% body weight; however, absorption of D-xylose, folate, and vitamin B12 was unaffected at any time point. Fat absorption postoperatively was only mildly abnormal (less than or equal to 8 g/day) at all time points in five of seven dogs despite complete lymphatic disruption. We concluded that jejunoileal autotransplantation does not markedly affect these specific jejunoileal absorptive functions. Fat absorption in most dogs surprisingly remains almost normal. Anatomic and physiologic consequences of intestinal transplantation do not appear to induce global abnormalities in all absorptive functions in the nonrejecting jejunoileum.}, }
@article {pmid1744967, year = {1991}, author = {Hafiz, S and Syed, Y and Rauf, U and Qadr, B and Shahabuddin, M}, title = {Etiology and management of diarrhoeal diseases in Karachi.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {41}, number = {9}, pages = {211-213}, pmid = {1744967}, issn = {0030-9982}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Bacteria/isolation &amp; purification ; Bacterial Infections/drug therapy/*etiology/microbiology ; Bacteriological Techniques ; Diagnosis, Differential ; Diarrhea/drug therapy/*etiology/microbiology ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; }, abstract = {The incidence of diarrhoeal disease are very high in our population and bacterial etiology amounts to 43.55% of all cases. Pathogen such as Aeromonas hydrophila, Plesiomonas shigelloides, Yersinia enterocolitica and Campylobacter are also present in significant numbers, they make up 50% of bacterial causes. All enteric pathogens can be easily isolated on commonly used media and could be precisely identified by simple biochemical tests.}, }
@article {pmid1684194, year = {1991}, author = {van Saene, HK and Percival, A}, title = {Bowel microorganisms--a target for selective antimicrobial control.}, journal = {The Journal of hospital infection}, volume = {19 Suppl C}, number = {}, pages = {19-41}, doi = {10.1016/0195-6701(91)90166-6}, pmid = {1684194}, issn = {0195-6701}, mesh = {4-Quinolones ; Anti-Bacterial Agents/administration &amp; dosage/*therapeutic use ; Anti-Infective Agents/therapeutic use ; Carrier State/prevention &amp; control ; Dose-Response Relationship, Drug ; Gram-Negative Bacteria/*drug effects ; Humans ; Intestine, Large/*microbiology ; Patient Compliance ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use ; }, abstract = {This article reviews the eight factors that determine the outcome of selective antimicrobial control (SAC) a technique aimed at the clearance of intestinal Gram-negative bacillary carriage by means of lethal faecal anti-microbial concentrations. They are as follows: (i) the carrier state; (ii) compliance; (iii) SAC aiming at prophylaxis vs treatment; (iv) minimum bactericidal concentration (MBC) of the antimicrobial; (v) dosage; (vi) pharmacokinetics; (vii) faecal inactivation; and (viii) microorganisms to be controlled. In the second part, non-absorbable SAC regimens are compared with absorbable trimethoprim/sulphamethoxazole (TMP/SMZ) and the fluoroquinolones in different clinical settings including neutropenia, intensive care, hepatic encephalopathy, liver transplantation and the salmonella carrier state. Ablation of gut carriage and superinfections are the main endpoints reviewed in this article. The newer fluoroquinolones are potent SAC agents to deal with enterobacteria. Pseudomonads are the major gap in their SAC spectrum. TMP/SMZ emerges as a SAC agent of limited value, whilst the newer non-absorbable combination of polymyxin/tobramycin seems to be the most potent SAC programme since it has activity against pseudomonads. In a third part, three current issues--the emergence of resistance, the selectivity and the tissue effect are discussed. Finally, a potent fluoroquinolone combined with oral polymyxin/tobramycin seems to be the most effective SAC programme currently available to control enterobacteria and pseudomonads in patients in whom bacterial translocation is a risk with minimal risk of resistance emerging.}, }
@article {pmid1865267, year = {1991}, author = {Yamada, M and Matsuda, S and Nakazawa, M and Arizono, N}, title = {Species-specific differences in heterogonic development of serially transferred free-living generations of Strongyloides planiceps and Strongyloides stercoralis.}, journal = {The Journal of parasitology}, volume = {77}, number = {4}, pages = {592-594}, pmid = {1865267}, issn = {0022-3395}, mesh = {Animals ; Feces/parasitology ; Female ; Species Specificity ; Strongyloidea/*growth &amp; development ; }, abstract = {The direction of free-living development (homogonic vs. heterogonic) in Strongyloides stercoralis and Strongyloides planiceps was examined by successive transplantation of the uterine eggs of free-living females into a test tube culture system containing fresh feces. The eggs from the first-generation free-living females of S. stercoralis did not develop into second-generation free-living adult worms, but all developed into filariform larvae. However, the majority of S. planiceps eggs from the first-generation free-living females developed into second-generation free-living adults. By successive transfer of uterine eggs of each generation, 9 generations developed, and in every cycle more adult worms developed than filariform larvae. However, the number of free-living generations was not infinite; in experiments repeated twice, the number of worms developing from the eggs of eighth or ninth generations was too small to continue further culture. These findings indicate that the pattern of free-living development is different between the 2 species.}, }
@article {pmid1682365, year = {1991}, author = {van Saene, HK and Stoutenbeek, CP and Hart, CA}, title = {Selective decontamination of the digestive tract (SDD) in intensive care patients: a critical evaluation of the clinical, bacteriological and epidemiological benefits.}, journal = {The Journal of hospital infection}, volume = {18}, number = {4}, pages = {261-277}, doi = {10.1016/0195-6701(91)90184-a}, pmid = {1682365}, issn = {0195-6701}, mesh = {Carrier State/*drug therapy/epidemiology/prevention &amp; control ; Clinical Trials as Topic ; Cohort Studies ; Critical Care/*methods ; Cross Infection/*drug therapy/epidemiology/prevention &amp; control ; Disease Outbreaks/*prevention &amp; control/statistics &amp; numerical data ; Drug Resistance, Microbial ; Gastrointestinal Diseases/*drug therapy/epidemiology/prevention &amp; control ; Humans ; Infection Control/methods ; Infections/*drug therapy/epidemiology ; Meta-Analysis as Topic ; Morbidity ; Mortality ; }, abstract = {Twenty trials (17 controlled and three observational cohort studies) on selective decontamination of the digestive tract (SDD) have been undertaken to date. SDD is defined as a technique which aims to eradicate carriage of disease-causing microorganisms by means of lethal oropharyngeal and faecal antimicrobial concentrations. The SDD concept and the criteria for the choice of the antimicrobials used in the SDD programme are explained. Abolition of the carrier state is thought to provide clinical, bacteriological and epidemiological benefits. Infection-specific morbidity and mortality, emergence of antibiotic resistance and outbreaks are the main endpoints evaluated in this review. Of the 15 controlled studies that considered carriage, 14 demonstrated a significant reduction of Gram-negative bacillary (GNB) carriage. Severe infections, including pneumonia and septicaemia, caused by enterobacteria and pseudomonads have been virtually eliminated in these trials. Five of the 12 centres that evaluated mortality showed a significant decrease among patients who received SDD. Two recent trials describe the control of an outbreak with a multiresistant Klebsiella by SDD. There are three indications for the use of SDD so far: (i) in trauma patients; (ii) in certain elective surgical procedures including liver transplantation and oesophageal resection; and (iii) in control of outbreaks of ICU infection. Future lines of research may include a properly designed trial with mortality as endpoint and studies on the transfer of SDD from the ICU into the ward as part of prophylaxis in major surgery.}, }
@article {pmid2019380, year = {1991}, author = {Herbert, A and Corbin, D and Williams, A and Thompson, D and Buckels, J and Elias, E}, title = {Erythropoietic protoporphyria: unusual skin and neurological problems after liver transplantation.}, journal = {Gastroenterology}, volume = {100}, number = {6}, pages = {1753-1757}, doi = {10.1016/0016-5085(91)90680-j}, pmid = {2019380}, issn = {0016-5085}, mesh = {Adult ; Burns/etiology ; Female ; Humans ; Intraoperative Period ; Lighting/adverse effects ; Liver Diseases/*surgery ; Liver Transplantation/*pathology ; Operating Rooms ; Photosensitivity Disorders/*etiology ; Polyneuropathies/*etiology ; Porphyrias/*surgery ; Postoperative Complications/*etiology ; }, abstract = {The case of a woman with protoporphyria who developed liver failure and underwent liver transplantation is described. During the pretransplant episode of liver failure she developed quadriparesis that rapidly progressed after transplantation to a severe polyneuropathy. Following transplantation she also developed a second-degree burn of the light-exposed abdominal wall. The neuropathy resembled that observed in other forms of porphyria, and it is proposed that the extreme disturbance of protoporphyrin levels associated with protoporphyrin-induced liver failure caused this neuropathy. Such a neuropathy has not previously been described in protoporphyria. Erythrocyte protoporphyrin levels remain high and fecal levels normal, although results of liver tests are normal. She remains photosensitive, which emphasizes that although liver transplantation may be lifesaving in this disorder, it is not curative, and care must be taken to prevent photosensitive damage to skin and light-exposed internal organs.}, }
@article {pmid1826901, year = {1991}, author = {Peng, Q and Moan, J and Kongshaug, M and Evensen, JF and Anholt, H and Rimington, C}, title = {Sensitizer for photodynamic therapy of cancer: a comparison of the tissue distribution of Photofrin II and aluminum phthalocyanine tetrasulfonate in nude mice bearing a human malignant tumor.}, journal = {International journal of cancer}, volume = {48}, number = {2}, pages = {258-264}, doi = {10.1002/ijc.2910480218}, pmid = {1826901}, issn = {0020-7136}, mesh = {Animals ; Dihematoporphyrin Ether ; Female ; Hematoporphyrin Photoradiation ; Hematoporphyrins/*pharmacokinetics/therapeutic use ; Humans ; Indoles/*pharmacokinetics/therapeutic use ; Laser Therapy ; Melanoma, Experimental/*drug therapy/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Organometallic Compounds/*pharmacokinetics/therapeutic use ; Photochemotherapy/*methods ; Tissue Distribution ; }, abstract = {The distribution of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AIPCS4) in tissues of BALB/c nu/nu nude mice bearing the LOX human melanoma was measured fluorimetrically at different times after intraperitoneal injection of the drugs, 20 mg/kg body weight. The plasma levels of the drugs as well as the excretion in feces and urine were also determined. The plasma concentrations of both drugs were found to build up in a similar manner during the first 30 min after injection. Thereafter, the plasma level of AIPCS4 decreased exponentially with an elimination half-life of 1.5 hr. The kinetics of elimination of P-II from the plasma were consistent with a 2-compartment model, with 90% of sensitizer lost with a half-life of about 5 hr, and the remaining fraction with a half-life of 30 hr. About 80% of the injected dose of P-II was excreted in the feces during the 7-days following injection, while 77% of AIPCS4 was excreted in the urine during the same period. After injection of a dose of 20 mg/kg, the concentrations of P-II in the LOX tumor as well as in the skin, muscle, brain, heart, lung, kidney and liver increased for about 24 hr, then remained constant or decreased slowly for the next 48 hr, after which they decreased slightly faster. On the other hand, the concentrations of APICS4 in most tissues as well as in the tumor peaked at about 30 min, then decreased with a half-life of between 1.5 and 3 hr. The tumor/skin concentration ratio was about 1 for both drugs (1-24 hr after injection). The tumor/muscle concentration ratio was about 2 for P-II at all sampling times, and maximally 10 (at 18 hr after injection) for AIPCS4. In the present tumor model, the tumor/tissue concentration ratio for all tissues at 1 hr and at 24 hr after the injection was equal for the 2 drugs or higher for AIPCS4.}, }
@article {pmid1679075, year = {1991}, author = {Peigue-Lafeuille, H and Henquell, C and Chambon, M and Gazuy, N and De Champs, C and Cluzel, R}, title = {Nosocomial rotavirus infections in adult renal transplant recipients.}, journal = {The Journal of hospital infection}, volume = {18}, number = {1}, pages = {67-70}, doi = {10.1016/0195-6701(91)90095-p}, pmid = {1679075}, issn = {0195-6701}, mesh = {Adult ; Cross Infection/*epidemiology/microbiology ; Feces/microbiology ; Humans ; *Kidney Transplantation ; Rotavirus Infections/*epidemiology/microbiology ; }, abstract = {We conducted a 24-month survey of hospital-acquired rotavirus infections in 20 renal transplant recipients who received their graft during 1988. Four cases of nosocomial rotavirus infection were diagnosed (20% of patients), 3-34 days after graft. Two patients presented with severe diarrhoea and two with fever alone. The cases occurred mainly during the winter months and remained sporadic. None of our patients was found to have chronic excretion of rotaviruses. Contacts from paediatric cases can be ruled out. We concluded that rotavirus nosocomial infections were frequent in adult renal transplant recipients and suggest that screening for rotavirus is regularly performed in these immunodeficient patients who are very susceptible to hypovolaemia.}, }
@article {pmid2014547, year = {1991}, author = {Gregory, CR and Gourley, IM and Cain, GR and Patz, JD and Imondi, KA and Martin, JA}, title = {Mizoribine serum levels associated with enterotoxicity in the dog.}, journal = {Transplantation}, volume = {51}, number = {4}, pages = {877-881}, doi = {10.1097/00007890-199104000-00027}, pmid = {2014547}, issn = {0041-1337}, mesh = {Animals ; Cyclosporins/administration &amp; dosage/pharmacology ; Dogs ; Drug Synergism ; Enteritis/*chemically induced ; Female ; Graft Survival ; Immunosuppressive Agents/*toxicity ; Intestines/*drug effects ; Kidney Transplantation/immunology/*physiology ; Ribonucleosides/blood/*toxicity ; Transplantation, Homologous ; }, abstract = {To prevent or minimize mizoribine enterotoxicity in organ transplant recipients and to differentiate mizoribine enterotoxicity from other causes of enteritis, serum levels of mizoribine that produced subclinical and clinical signs of enterotoxicity were determined in the dog. When mizoribine was administered orally at 12-hr intervals, half the dogs studied showed clinical evidence of gastrointestinal disturbances (vomiting, diarrhea, and anorexia) without histopathologic signs of enterotoxicity. Using a 24-hr oral-dose schedule, clinical signs of gastrointestinal disturbances and histopathologic evidence (mucosal degeneration, crypt degeneration, and necrosis) of enterotoxicity were encountered when the mean 12-hr mizoribine serum level was 0.97 +/- 0.4 microgram/ml or greater. Histopathologic signs of enterotoxicity with repeated positive fecal occult blood assays and without clinical signs of gastrointestinal disturbances occurred when the mean 12-hr serum level was 0.53 +/- 0.17 microgram/ml or greater. Oral administration of cyclosporine did not exacerbate mizoribine enterotoxicity in the dog when administered with mizoribine at a dose that produced histopathologic signs of enterotoxicity.}, }
@article {pmid1993449, year = {1991}, author = {MacGowan, AP and Marshall, RJ and MacKay, IM and Reeves, DS}, title = {Listeria faecal carriage by renal transplant recipients, haemodialysis patients and patients in general practice: its relation to season, drug therapy, foreign travel, animal exposure and diet.}, journal = {Epidemiology and infection}, volume = {106}, number = {1}, pages = {157-166}, pmid = {1993449}, issn = {0950-2688}, mesh = {Animals ; Animals, Domestic ; Carrier State/*epidemiology ; Cats ; Cheese ; Feces/microbiology ; Food ; Gastroenteritis/*epidemiology ; Humans ; Immunosuppression Therapy ; *Kidney Transplantation ; Listeria/isolation &amp; purification ; Listeriosis/*epidemiology ; Ranitidine/therapeutic use ; *Renal Dialysis ; Risk Factors ; Seasons ; Surveys and Questionnaires ; Travel ; }, abstract = {About 2.3% (16/700) of faecal specimens from renal transplant recipients and patients having home haemodialysis as well as patients attending their general practitioners with symptoms of gastroenteritis yielded Listeria species 40% of positive faeces contained more than one Listeria species or serovar. The proportion of positive specimens was similar in all three patient groups. Listeria were isolated from 5.6% (10/177) of renal transplant recipients on one or more occasions over the period of a year. The commonest species was L. monocytogenes and type 4b the commonest serovar. Carriage was more common in July and August than other times of year, and less than 28 weeks in duration. In renal transplant recipients carriage was positively related to treatment with ranitidine, consumption of more than three types of cheese in the previous 20 months, and consumption of English cheddar cheese more than once per week.}, }
@article {pmid1989265, year = {1991}, author = {Badger, IL and Crosby, HA and Kong, KL and Baker, JP and Hutchings, P and Elliott, TS and McMaster, P and Bion, JF and Buckels, JA}, title = {Is selective decontamination of the digestive tract beneficial in liver transplant patients? Interim results of a prospective, randomized trial.}, journal = {Transplantation proceedings}, volume = {23}, number = {1 Pt 2}, pages = {1460-1461}, pmid = {1989265}, issn = {0041-1345}, mesh = {Adult ; Anti-Bacterial Agents/administration &amp; dosage ; Bacterial Infections/complications ; Digestive System/*microbiology ; Endotoxins/blood ; Feces/microbiology ; Humans ; Liver Transplantation/*methods ; Prospective Studies ; }, }
@article {pmid2061770, year = {1991}, author = {Vajro, P and di Martino, L and Scotti, S and Barbati, C and Fontanella, A and Pettoello Mantovani, M}, title = {Intestinal Cryptosporidium carriage in two liver-transplanted children.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {12}, number = {1}, pages = {139}, doi = {10.1097/00005176-199101000-00026}, pmid = {2061770}, issn = {0277-2116}, mesh = {Carrier State ; Child ; Cryptosporidiosis/*diagnosis ; Feces/microbiology ; Female ; Humans ; Infant ; *Liver Transplantation ; Male ; }, }
@article {pmid2043517, year = {1991}, author = {Seiler, C and Fielding, G and Blumgart, LH and Triller, J and Schultheiss, HR}, title = {Rectal bleeding associated with chronic pancreatitis.}, journal = {HPB surgery : a world journal of hepatic, pancreatic and biliary surgery}, volume = {3}, number = {3}, pages = {199-203}, doi = {10.1155/1991/85468}, pmid = {2043517}, issn = {0894-8569}, mesh = {Adult ; Chronic Disease ; Colonic Diseases/complications ; Humans ; Intestinal Fistula/complications ; Male ; Melena/*etiology ; Middle Aged ; Pancreatic Fistula/complications ; Pancreatic Pseudocyst/complications ; Pancreatitis/*complications ; }, abstract = {Pseudocyst formation, with its attendant complications of compression, rupture, bleeding and fistula formation, is a well known complication of chronic pancreatitis. In 1966 Berne and Edmondson drew attention to the often fatal outcome of pancreatico-colonic fistula complicated by hemorrhage. We present two cases of this rare complication of chronic pancreatitis as defined by the Marseille classification.}, }
@article {pmid2004346, year = {1991}, author = {Prescott, JF}, title = {Rhodococcus equi: an animal and human pathogen.}, journal = {Clinical microbiology reviews}, volume = {4}, number = {1}, pages = {20-34}, pmid = {2004346}, issn = {0893-8512}, mesh = {Acquired Immunodeficiency Syndrome/*complications ; Actinomycetales Infections/complications/*microbiology/veterinary ; Animals ; Horse Diseases/*microbiology ; Horses ; Humans ; Immune Tolerance ; Pneumonia/complications/*microbiology/veterinary ; Rhodococcus/*pathogenicity ; }, abstract = {Recent isolations of Rhodococcus equi from cavitatory pulmonary disease in patients with AIDS have aroused interest among medical microbiologists in this unusual organism. Earlier isolations from humans had also been in immunosuppressed patients following hemolymphatic tumors or renal transplantation. This organism has been recognized for many years as a cause of a serious pyogranulomatous pneumonia of young foals and is occasionally isolated from granulomatous lesions in several other species, in some cases following immunosuppression. The last decade has seen many advances in understanding of the epidemiology, pathogenesis, diagnosis, treatment, and immunity to infection in foals. The particular susceptibility of the foal is not understood but can be explained in part by a combination of heavy challenge through the respiratory route coinciding with declining maternally derived antibody in the absence of fully competent foal cellular immune mechanisms. R. equi is largely a soil organism but is widespread in the feces of herbivores. Its growth in soil is considerably improved by simple nutrients it obtains from herbivore manure. About one-third of human patients who have developed R. equi infections had contact in some way with herbivores or their manure. Others may have acquired infection from contact with soil or wild bird manure. R. equi is an intracellular parasite, which explains the typical pyogranulomatous nature of R. equi infections, the predisposition to infection in human patients with defective cell-mediated immune mechanisms, and the efficacy of antimicrobial drugs that penetrate phagocytic cells.}, }
@article {pmid1952507, year = {1991}, author = {Ruggiero, R and Trerè, M and Ciliberti, M and Iovino, G}, title = {[The smooth muscle autograft in continent colostomies. Experimental research on rabbits].}, journal = {Annali italiani di chirurgia}, volume = {62}, number = {1}, pages = {75-9; discussion 79-80}, pmid = {1952507}, issn = {0003-469X}, mesh = {Animals ; Colon/diagnostic imaging ; Colostomy/*methods ; Fecal Incontinence/prevention &amp; control ; Muscle, Smooth/*transplantation ; Rabbits ; Radiography ; Suture Techniques ; Transplantation, Autologous ; }, abstract = {The authors stop onto make use of the colon smooth musculature to resolve the question of medical and surgical methods used until now to improve the continence of colostomies. Owing to the experiences and co-operating with some other research centers, the authors refer about the experiment performed on the rabbit, where a small leaf of intestine serous-muscular tissue was employed to perform a continence system on colostomy. The analysis of manometric results obtained from check animals in different post-operatory periods (3-7-14-21 days) pointed out a moderate reaction of neosphincterial function, while the histological results prove a favorable histological development without to change the muscular tunica fibrous tissue. The easy application, harmless of employed methods and undoubted comfort for the patient stand for valid indications in the development to come of this method.}, }
@article {pmid1825238, year = {1991}, author = {Ditrich, O and Palkovic, L and Stĕrba, J and Prokopic, J and Loudová, J and Giboda, M}, title = {The first finding of Cryptosporidium baileyi in man.}, journal = {Parasitology research}, volume = {77}, number = {1}, pages = {44-47}, pmid = {1825238}, issn = {0932-0113}, mesh = {Animals ; Animals, Suckling ; Chickens ; Cryptosporidiosis/complications/*parasitology ; Cryptosporidium/*isolation &amp; purification/ultrastructure ; Esophagus/parasitology ; Feces/parasitology ; Gallbladder/parasitology ; HIV Infections/*complications ; Humans ; Intestines/parasitology ; Male ; Mice ; Mice, Inbred ICR ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Opportunistic Infections/*complications ; Respiratory System/parasitology ; Specific Pathogen-Free Organisms ; Urinary Bladder/parasitology ; }, abstract = {Oocysts of cryptosporidia whose morphology and measurements corresponded with those of the species Cryptosporidium baileyi were found in the stool of an immunodeficient patient. In autopsy material, cryptosporidia were found in the esophagus, whole intestine, trachea, larynx, lungs, and gall and urinary bladders. None of the 69 suckling mice inoculated with this isolate developed cryptosporidial infection. Infection was successful in 26 chickens inoculated perorally and 6 others subjected to intratracheal inoculation; it was localized in the duodenum, jejunum, bursa Fabricii, and respiratory tract. From day 12 after infection, oocysts of cryptosporidia were found in the excrement. Human infection with C. baileyi may have occurred due to disruption of the immune system by human immunodeficiency virus (HIV) and to immunosuppressive therapy undertaken after allogeneic kidney transplantation.}, }
@article {pmid2278127, year = {1990}, author = {Rosol, TJ and Stromberg, PC}, title = {Effects of large granular lymphocyte leukemia on bone in F344 rats.}, journal = {Veterinary pathology}, volume = {27}, number = {6}, pages = {391-396}, doi = {10.1177/030098589902700602}, pmid = {2278127}, issn = {0300-9858}, mesh = {Animals ; Body Weight ; *Bone Development ; Bone and Bones/*pathology ; Calcium/blood/urine ; Disease Models, Animal ; Eating ; Feces ; Lumbar Vertebrae/pathology ; Male ; Neoplasm Transplantation ; Organ Size ; Osteoclasts ; Phosphorus/blood/urine ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*pathology ; Rats ; Rats, Inbred F344 ; Spleen/pathology ; Urine ; }, abstract = {Large granular lymphocyte (LGL) leukemia was induced in 40 F344 rats by inoculating them with neoplastic cells to evaluate the effect of acute leukemia on bone remodeling and calcium balance. The rats developed leukemia and splenomegaly by 9 days after inoculation. The rats had reduced body weight (day 12), food intake (days 4, 8, 12), urine production (day 12), and fecal output (day 12). Serum calcium and phosphorus and urinary excretion of calcium and phosphorus were decreased on days 8 and 12 in leukemic rats. Static bone histomorphometry of trabecular bone in lumbar vertebrae demonstrated reduced bone area, no change in the number of osteoclasts, and reduced osteoclast perimeter at day 12. Dynamic bone histomorphometry revealed reduced double labeled perimeter, mineralizing perimeter, trabecular mineral appositional rate, and bone formation rate in rats with LGL leukemia at days 9 and 12. There was no change in periosteal mineral appositional rate. Rats with leukemia and intramedullary neoplastic cells had a reduction in bone formation rate that resulted in a loss of trabecular bone.}, }
@article {pmid2393864, year = {1990}, author = {Longley, C and Furmanski, P and Dienhart, DG and Lear, J and Bloedow, D and Kasliwal, R and Bunn, PA}, title = {Pharmacokinetics, biodistribution, and gamma camera imaging of 111In-KC-4G3 murine monoclonal antibody in athymic nude mice with or without human tumor xenografts.}, journal = {Cancer research}, volume = {50}, number = {18}, pages = {5954-5961}, pmid = {2393864}, issn = {0008-5472}, support = {CA46088/CA/NCI NIH HHS/United States ; CA46934/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Antibodies, Monoclonal/pharmacokinetics ; Antigens, Neoplasm/*analysis/immunology ; Humans ; *Indium Radioisotopes ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mucins/*analysis/immunology ; Neoplasm Transplantation ; Neoplasms, Experimental/diagnostic imaging/*immunology ; Radionuclide Imaging ; Tissue Distribution ; Transplantation, Heterologous ; }, abstract = {The pharmacokinetics and tissue distribution of the monoclonal antibody radioconjugate 111In-diethylenetriaminepentaacetic acid-KC-4G3, which is directed against a high molecular weight mucin(s) antigen expressed on the human milk fat globule and many epithelial cell membranes, were examined in BALB/c nude mice with and without xenografts of the human tumor lines ZR-75 (mammary adenocarcinoma, KC-4G3 antigen positive) and BALL-1 (B-cell lymphoma, KC-4G3 antigen negative). Plasma of ZR-75 and BALL-1 tumor-bearing nude mice inoculated with 111In-KC-4G3 had a higher initial volume of distribution (V1), steady state volume of distribution (Vss), and plasma clearance and a lower initial half-life (t1/2 alpha) than non-tumor-bearing nude mice. There were no significant differences in biological half-life (t1/2 beta) in tumor- and non-tumor-bearing nude mice. Urinary and fecal excretion of radioactivity by ZR-75 tumor-bearing mice was greater than that of BALL-1 and non-tumor-bearing mice. Localization of 111In-KC-4G3 in mice bearing xenografts of ZR-75 was significantly greater than in mice with BALL-1 tumors. Uptake of 111In-KC-4G3 by ZR-75 tumors averaged 14% of injected dose/g at 72 h after inoculation and was unaffected by antibody dose. Significantly, the radioconjugate concentration in ZR-75 tumors remained relatively constant from 72 to 336 h post-inoculation, while that in normal tissues declined considerably over this period. Nonspecific reticuloendothelial tissue uptake of 111In-KC-4G3 was only moderately affected by pretreatment with a large excess of unlabeled normal mouse immunoglobulin and was not changed by treatment with asialofetuin. Further enhancement of specific localization of 111In-KC-4G3 was obtained by subtraction of the blood pool identified by co-inoculation of 131I-labeled, isotype-identical, normal mouse immunoglobulin. Gamma camera images of 111In-KC-4G3-inoculated ZR-75 tumor-bearing mice showed enhanced tumor localization compared to mice with BALL-1 tumors. The results of this study suggest that 111In-KC-4G3 may prove useful for imaging and possibly therapy of human malignancies expressing the high molecular weight epithelial mucin(s).}, }
@article {pmid2228830, year = {1990}, author = {Murdoch, DA and Gibbs, S and Price, CG and Easmon, S and Franklin, J and Lister, TA and Tabaqchali, S}, title = {Effect of ceftazidime and gentamicin on the oropharyngeal and faecal flora of patients with haematological malignancies.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {26}, number = {3}, pages = {419-428}, doi = {10.1093/jac/26.3.419}, pmid = {2228830}, issn = {0305-7453}, mesh = {Ceftazidime/*pharmacology ; Colistin/therapeutic use ; Enterobacter/drug effects/isolation &amp; purification ; Feces/*microbiology ; Gentamicins/*pharmacology ; Humans ; Leukemia, Myeloid, Acute/drug therapy/*microbiology ; Lymphoma, Non-Hodgkin/drug therapy/*microbiology ; Neutropenia/drug therapy/*microbiology ; Nystatin/therapeutic use ; Oropharynx/*microbiology ; Risk Factors ; Staphylococcus/drug effects/enzymology/isolation &amp; purification ; Streptococcus/drug effects/isolation &amp; purification ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use ; }, abstract = {Thirty-four patients with haematological malignancies were studied to investigate the effect of empirical broad-spectrum antibiotic therapy (ceftazidime and gentamicin) on the gastro-intestinal flora. Twenty-five patients with acute myeloid leukaemia or post-autologous bone-marrow transplantation were given framycetin, nystatin and colistin (Fracon), and two patients with non-Hodgkin's Lymphoma were on co-trimoxazole, as long-term gut prophylaxis. Semi-quantitative microbiology was carried out on oropharyngeal swabs and quantitative microbiology on faecal specimens. The oropharyngeal flora consisted mainly of streptococci, coagulase-negative staphylococci and coryneforms, and was little affected by ceftazidime/gentamicin. A strain of Enterobacter cloacae resistant to ceftazidime and gentamicin colonized one patient, who later developed septicaemia. The faecal flora of patients on Fracon was dominated by enterococci; the few enterobacteria present were eliminated by ceftazidime/gentamicin. The anaerobic flora was absent in 15% of patients; in the remainder, it consisted mainly of Bacteroides spp., and was little affected by ceftazidime/gentamicin. The faecal flora of patients not on Fracon always contained anaerobes, and some strains of enterobacteria persisted throughout antibiotic treatment. None of the patients was colonized by Clostridium difficile or Pseudomonas aeruginosa. Broad-spectrum therapy with ceftazidime and gentamicin appeared to have little effect on the gastro-intestinal flora, except to encourage the overgrowth of enterococci and reduce the numbers of enterobacteria.}, }
@article {pmid2207570, year = {1990}, author = {Christiansen, J and Sørensen, M and Rasmussen, OO}, title = {Gracilis muscle transposition for faecal incontinence.}, journal = {The British journal of surgery}, volume = {77}, number = {9}, pages = {1039-1040}, doi = {10.1002/bjs.1800770928}, pmid = {2207570}, issn = {0007-1323}, mesh = {Adolescent ; Adult ; Anal Canal/physiopathology ; Fecal Incontinence/physiopathology/*surgery ; Female ; Humans ; Male ; Middle Aged ; Muscles/*transplantation ; Physical Therapy Modalities ; Postoperative Care ; Pressure ; Thigh ; }, abstract = {Transposition of the gracilis muscle for faecal incontinence was performed in 13 patients. Six gained satisfactory continence, four were improved, two did not benefit from the operation and one patient died from intercurrent disease before closure of a pre-existing colostomy. Anal manometry compared with a control group showed no alteration in resting and pressure at a median of 35 mmHg (range 5-63 mmHg), whereas maximum squeeze pressure increased from a median of 38 mmHg (range 5-79 mmHg) to 59 mmHg (range 10-143 mmHg) (P = 0.041) which was, however, significantly lower than 130 mmHg (range 81-236 mmHg) in the control group. All patients who benefited from the operation had an increase in maximum squeeze pressure. The ability to retain a viscous fluid in the rectum was measured in seven patients, four of whom had gained satisfactory continence and three of whom had improved continence. They were able to retain a median volume of 200 ml (range 50-225 ml) without leakage compared with 325 ml (range 250-400 ml) in the control group. These patients could retain the maximum amount of viscous fluid for 5-8 min, whereas all control subjects could do so for more than 15 min. It is concluded that, although gracilis transposition never results in normal continence, acceptable continence may be achieved in selected patients provided careful attention is paid to the technical details of the procedure and provided that systematic postoperative exercises are performed.}, }
@article {pmid1974652, year = {1990}, author = {Dharakul, T and Rott, L and Greenberg, HB}, title = {Recovery from chronic rotavirus infection in mice with severe combined immunodeficiency: virus clearance mediated by adoptive transfer of immune CD8+ T lymphocytes.}, journal = {Journal of virology}, volume = {64}, number = {9}, pages = {4375-4382}, pmid = {1974652}, issn = {0022-538X}, support = {DK38707-01/DK/NIDDK NIH HHS/United States ; R22 AI121362-06/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigens, Differentiation, T-Lymphocyte/*immunology ; Antigens, Surface/analysis/immunology ; Antigens, Viral/analysis ; CD8 Antigens ; Enzyme-Linked Immunosorbent Assay ; Feces/microbiology ; Female ; *Immunization, Passive ; Immunoenzyme Techniques ; Immunologic Deficiency Syndromes/*complications/immunology ; Major Histocompatibility Complex ; Mice ; Mice, Inbred BALB C ; Mice, Mutant Strains ; Rotavirus/isolation &amp; purification ; Rotavirus Infections/complications/*immunology ; Spleen/immunology ; T-Lymphocytes/*immunology/transplantation ; Thy-1 Antigens ; }, abstract = {Severe combined immunodeficient (SCID) mice lack both functional T and B cells. These mice develop chronic rotavirus infection following an oral inoculation with the epizootic diarrhea of infant mice (EDIM) rotavirus. Reconstitution of rotavirus-infected SCID mice with T lymphocytes from immunocompetent mice allows an evaluation of a role of T-cell-mediated immunity in clearing chronic rotavirus infection. Complete rotavirus clearance was demonstrated in C.B-17/scid mice 7 to 9 days after the transfer of immune CD8+ splenic T lymphocytes from histocompatible BALB/c mice previously immunized intraperitoneally with the EDIM-w strain of murine rotavirus. The virus clearance mediated by T-cell transfer was restricted to H-2d-bearing T cells and occurred in the absence of rotavirus-specific antibody as determined by enzyme-linked immunosorbent assay, neutralization, immunohistochemistry, and radioimmunoprecipitation. Temporary clearance of rotavirus was observed after the transfer of immune CD8+ T cells isolated from the intestinal mucosa (intraepithelial lymphocytes [IELs]) or the spleens of BALB/c mice previously infected with EDIM by the oral route. Chronic virus shedding was transiently eliminated 7 to 11 days after spleen cell transfer and 11 to 12 days after IEL transfer. However, recurrence of rotavirus infection was detected 1 to 8 days later in all but one SCID recipient receiving cells from orally immunized donors. The viral clearance was mediated by IELs that were both Thy1+ and CD8+. These data demonstrated that the clearance of chronic rotavirus infection in SCID mice can be mediated by immune CD8+ T lymphocytes and that this clearance can occur in the absence of virus-specific antibodies.}, }
@article {pmid2401686, year = {1990}, author = {Alghanem, AA and McCauley, RL and Robson, MC and Rutan, RL and Herndon, DN}, title = {Management of pediatric perineal and genital burns: twenty-year review.}, journal = {The Journal of burn care &amp; rehabilitation}, volume = {11}, number = {4}, pages = {308-311}, doi = {10.1097/00004630-199007000-00007}, pmid = {2401686}, issn = {0273-8481}, mesh = {Burns/epidemiology/*surgery ; Child ; Child, Preschool ; Contracture/surgery ; Female ; Follow-Up Studies ; Genitalia/*injuries ; Humans ; Male ; Perineum/*injuries ; Retrospective Studies ; Skin Transplantation ; Surgery, Plastic ; Surgical Flaps ; Time Factors ; }, abstract = {Between 1966 and 1986, fifty-seven pediatric patients with partial and/or full-thickness perineal and genital burns with a minimum of 1-year follow-up were identified. Fifty percent of the patients with genital burns and 20% of the patients with perineal and/or buttock burns required skin grafting in the acute stage. No patient required suprapubic cystostomies, diverting colostomies, or local flap coverage of exposed testicles. Burn scar contractures were the most frequent complications. Thirty-two patients (56%) required contracture release of the perineum and coverage with either skin grafts or local skin flaps. In three patients (6%) contracture required release of the penis and scrotum. One patient lost a testicle. Three patients developed rectal prolapse and were treated without surgery. Four patients developed rectal stenosis with fecal incontinence because of burn scar contracture and were treated by anal dilatation, local transposition flaps, and/or excision of the scar and primary closure. Acute management of pediatric patients with such injuries can be conservative. Delayed complications of contractures of the perineum and genitals can be easily corrected with scar excisions, skin grafts, or the use of local skin flaps.}, }
@article {pmid2190375, year = {1990}, author = {Lemaire, M and Fahr, A and Maurer, G}, title = {Pharmacokinetics of cyclosporine: inter- and intra-individual variations and metabolic pathways.}, journal = {Transplantation proceedings}, volume = {22}, number = {3}, pages = {1110-1112}, pmid = {2190375}, issn = {0041-1345}, mesh = {Bile/metabolism ; Cyclosporins/*pharmacokinetics ; Drug Interactions ; Feces/analysis ; Female ; Humans ; Intestinal Absorption/physiology ; Male ; Metabolic Clearance Rate/physiology ; Tissue Distribution/physiology ; }, }
@article {pmid2378152, year = {1990}, author = {Knöll, R and Reinel, D and Bothe, C and Tsolkas, P}, title = {[Fungal involvement of the tongue and feces in dialysis-dependent patients].}, journal = {Zeitschrift fur Hautkrankheiten}, volume = {65}, number = {5}, pages = {476-480}, pmid = {2378152}, issn = {0301-0481}, mesh = {Adult ; Aged ; Aged, 80 and over ; Candidiasis, Oral/microbiology ; Feces/*microbiology ; Female ; Fungi/isolation &amp; purification ; Glossitis/*microbiology ; Humans ; Kidney Failure, Chronic/*therapy ; Kidney Transplantation/*immunology ; Male ; Middle Aged ; Mycoses/*microbiology ; Opportunistic Infections/*microbiology ; *Renal Dialysis ; Risk Factors ; Tongue/microbiology ; }, abstract = {38 patients regularly receiving dialysis and 3 patients with a renal transplant were investigated with regard to possible colonization of yeasts. The tongue and stool were directly examined with Kimmig agar, the resulting yeasts were then differentiated by means of rice agar and an auxanogram. Candida albicans was the germ most frequently found both on the tongue (47.5%) and in the stool (50%). We discuss the significance of our results.}, }
@article {pmid2363327, year = {1990}, author = {Stoye, M and Ising, S and Reisewitz, K}, title = {[Transplanted infections with Toxocara canis as a model for the effectiveness testing of anthelmintics].}, journal = {Zentralblatt fur Veterinarmedizin. Reihe B. Journal of veterinary medicine. Series B}, volume = {37}, number = {2}, pages = {81-90}, pmid = {2363327}, issn = {0514-7166}, mesh = {Animals ; Anthelmintics/*therapeutic use ; Disease Models, Animal ; Dog Diseases/*drug therapy ; Dogs ; Feces/parasitology ; Male ; Toxocara/growth &amp; development ; Toxocariasis/drug therapy/*veterinary ; }, abstract = {Patent infections of adult dogs with Toxocara canis induced by transplantation of immature, intestinal stages were examined for their suitability for testing of anthelmintics. Each of 5 dogs were infected four times by transplantation of 80 immature, intestinal stages of Toxocara canis. The dogs were treated with various anthelmintics of well established efficacy (pyrantel, nitroscanate, mebendazole, piperazine) 20 dpi. All anthelmintics tested showed the same efficacy as had been assessed earlier by treatment of dogs infected prenatally with Toxocara canis.}, }
@article {pmid2343206, year = {1990}, author = {Stone, WJ and Schaffner, W}, title = {Strongyloides infections in transplant recipients.}, journal = {Seminars in respiratory infections}, volume = {5}, number = {1}, pages = {58-64}, pmid = {2343206}, issn = {0882-0546}, mesh = {Adult ; Animals ; Humans ; Immunosuppression Therapy ; Kidney Transplantation/*adverse effects ; Male ; Pneumonia/drug therapy/etiology/parasitology ; Strongyloides/isolation &amp; purification ; *Strongyloidiasis/drug therapy/parasitology ; Thiabendazole/administration &amp; dosage/therapeutic use ; }, abstract = {Solid organ transplant recipients can experience serious disease and death from infection due to the parasitic roundworm Strongyloides stercoralis. This parasite lives in soil contaminated with human feces. Domestic dogs and cats may be another reservoir. Larvae can penetrate the skin, are carried hematogenously to the lungs, migrate up the bronchial tree, and then can be passed to the upper small intestine. Autoinfection occurs in the setting of immunosuppression when invasive larvae penetrate the gut wall and cause disseminated infection. Polymicrobial sepsis is sometimes seen due to enteric organisms adhering to the parasite. Transplant recipients are at highest risk during the first 3 months posttransplant. Many organ systems may be affected. Pulmonary symptoms include cough, wheezing, sputum production, dyspnea, hemoptysis, tachypneas, and pleuritic pain. Hyperinfection, an augmentation of the normal skin-lung-intestine life cycle, occurs in roughly two-thirds of infected transplant recipients, with dissemination in the remainder. Diagnosis is made primarily by examination of the stool or intestinal secretions for ova and parasites. Occasionally, parasites are noted in the sputum. New serologic tests show promise. The parasite may remain in the host for over 25 years before immunosuppression causes either dissemination or hyperinfection. Thiabendazole given for 3 to 7 days is the treatment of choice for organ transplant recipients. Repeat courses may be needed to eradicate infection.}, }
@article {pmid2334092, year = {1990}, author = {Willams, NS and Hallan, RI and Koeze, TH and Pilot, MA and Watkins, ES}, title = {Construction of a neoanal sphincter by transposition of the gracilis muscle and prolonged neuromuscular stimulation for the treatment of faecal incontinence.}, journal = {Annals of the Royal College of Surgeons of England}, volume = {72}, number = {2}, pages = {108-113}, pmid = {2334092}, issn = {0035-8843}, mesh = {Adult ; Aged ; Anal Canal/physiopathology/*surgery ; Electric Stimulation Therapy/instrumentation/*methods ; Fecal Incontinence/physiopathology/*surgery ; Female ; Humans ; Male ; Middle Aged ; Muscles/*transplantation ; Pressure ; Thigh ; }, abstract = {Six patients incapacitating faecal incontinence, in whom conventional treatment had either failed or was contraindicated, were treated by a new technique. A neonanal sphincter was constructed by transposing the gracilis muscle around the anal canal. Chronic neuromuscular stimulation via an implanted electrical stimulator was then used in an attempt to convert the muscle to a slow twitch fatigue resistant muscle. Physiological measurements suggested that this conversion had begun, enabling the neosphincter to mount a sustained contraction. Five patients had their covering stomas closed, and continence was improved in all of them. However, one patient could not cope psychologically with the stimulator, and another patient was continent for long periods only when the neosphincter was used in conjunction with a silastic plug. This new technique may benefit selected patients with incontinence whose only alternative would be a permanent stoma.}, }
@article {pmid2156006, year = {1990}, author = {Fagan, E and Yousef, G and Brahm, J and Garelick, H and Mann, G and Wolstenholme, A and Portmann, B and Harrison, T and Mowbray, JF and Mowat, A}, title = {Persistence of hepatitis A virus in fulminant hepatitis and after liver transplantation.}, journal = {Journal of medical virology}, volume = {30}, number = {2}, pages = {131-136}, doi = {10.1002/jmv.1890300210}, pmid = {2156006}, issn = {0146-6615}, mesh = {Adult ; *Carrier State/immunology ; Child ; DNA, Viral/*analysis ; Feces/microbiology ; Female ; Hepatitis A/complications/*immunology/surgery ; Hepatitis Antibodies/*analysis ; Hepatovirus/analysis/*immunology ; Humans ; Liver/microbiology ; Liver Diseases/etiology/immunology/surgery ; *Liver Transplantation ; Male ; }, abstract = {A peroxidase-labelled, specific mouse monoclonal antibody to hepatitis A virus (HAV) and an in situ hybridization technique (streptavidin-biotin-horseradish peroxidase reaction) with an HAV-specific cDNA probe (recombinant plasmid pAWHA comprising 1.8 kb of the HAV-specific cDNA, located toward the 3' end of the genome) were used to detect HAV in liver tissues in two patients with fulminant viral hepatitis type A treated by liver transplantation after a protracted (day 40: case 1) and relapsing (day 60: case 2) clinical course. HAV antigens and HAV-specific genomic sequences were detected in the hepatectomy tissues and in serial biopsies of the liver grafts through to final follow-up at 2 months (case 2) or death at 7 months after re-grafting for chronic rejection (case 1). In the fulminant liver parenchyma, numerous degenerating and some surviving hepatocytes were positive and randomly scattered. The immunoperoxidase staining was predominantly cytoplasmic and often granular. The localization of the cDNA probe was predominantly nuclear/perinuclear but was occasionally cytoplasmic. High-titre IgM-anti-HAV antibodies persisted until death (case 1) or resolution (5 months) of an acute hepatitis (case 2), which occurred at 2 months, accompanied by HAV antigen (ELISA), in stool. Intact replicating virus particles must have been present in one or more sites in each case, including extrahepatic locations, with a viraemia as the most likely explanation for subsequent reinfection of the grafts.}, }
@article {pmid1967664, year = {1990}, author = {Grant, D and Wall, W and Mimeault, R and Zhong, R and Ghent, C and Garcia, B and Stiller, C and Duff, J}, title = {Successful small-bowel/liver transplantation.}, journal = {Lancet (London, England)}, volume = {335}, number = {8683}, pages = {181-184}, doi = {10.1016/0140-6736(90)90275-a}, pmid = {1967664}, issn = {0140-6736}, mesh = {Adult ; Fats/analysis ; Feces/analysis ; Female ; Humans ; Intestine, Small/*transplantation ; Liver/metabolism ; *Liver Transplantation/adverse effects ; Malabsorption Syndromes/*surgery ; Monitoring, Immunologic ; Prognosis ; Reoperation ; Short Bowel Syndrome/*surgery ; Thoracotomy/adverse effects ; Xylose/urine ; }, abstract = {A patient with the short-gut syndrome and antithrombin III deficiency underwent small bowel and liver grafting a year ago. Transient, mild graft-versus-host disease and intestinal rejection occurred within 2 months of grafting and were easily managed. Parenteral nutrition was discontinued 8 weeks after surgery. The patient has maintained normal nutritional indices while on an unrestricted oral diet. Small-bowel/liver grafting is feasible for patients with the short-gut syndrome and associated liver disorders. Further experience is needed to determine the specific risks, benefits, and general applicability of this procedure.}, }
@article {pmid2281198, year = {1990}, author = {Kreuzer, M and Kirchgessner, M and Ascherl, R and Heinz, S and Meier, J and Maderholz, H}, title = {Quantitative effects of allogeneic small-bowel transplantation on nutrient digestion and on body protein balance as determined in vivo in rats.}, journal = {Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie}, volume = {190}, number = {5}, pages = {323-335}, doi = {10.1007/BF00000039}, pmid = {2281198}, issn = {0300-9130}, mesh = {Animals ; Cyclosporins/pharmacology ; Dietary Fats/metabolism ; Dietary Proteins/*metabolism ; *Digestion ; Female ; Graft Rejection ; *Intestinal Absorption ; Intestine, Small/*transplantation ; Male ; Minerals/metabolism ; Rats ; Rats, Inbred Strains ; Short Bowel Syndrome/*metabolism ; Transplantation, Heterotopic ; Transplantation, Homologous ; }, abstract = {Heterotopic and orthotopic small-bowel allotransplantation was carried out in Wistar rats using grafts reduced to one-half of the original length. Portocaval venous anastomoses and intestinal end-to-end anastomoses were performed. Animals either with complete or with partially reduced native small-bowel served as control. In a total of 51 rats, 88 quantitative in vivo measurements of apparent digestion and absorption of dietary dry matter, organic matter, energy, protein, fat, total ash, and glucose were carried out. Body protein retention was calculated from intake and losses with feces and urine. The digestion trials comprised 8 days of adaptation and 10 days of continual recording of nutrient balance data. In experiments 1 and 2, digestibility coefficients were obtained before and after transplantation within the same animals, untreated or initially treated with cyclosporine A after surgery. Similar groups of rats untreated, with partial resection and with transplantation of the small-bowel, followed by temporary cyclosporine treatment, were used in experiment 3. In experiment 4, rats with transplanted intestines from experiments 1 and 2 were subjected to a further digestion trial 4 to 6 months after the respective first trial. With transplantation of the small intestine, apparent digestion and absorption of nutrients, as well as protein retention, tended to be lower. Significant depression occurred in the digestion of fat and ash. In long-term survivors all parameters decreased further. The adverse effects on fat and ash digestion seemed to be pronounced when rejection occurred. Fecal fat excretion might therefore be an indication of dysfunction of small-bowel grafts. Digestion was less imparied if cyclosporine was applied, and part of the effects on digestion and protein balance could be attributed to the shortened bowel.}, }
@article {pmid2192225, year = {1990}, author = {De Macedo, A and Lee, S}, title = {Metabolic effect of pancreas transplantation on long-term diabetic rats.}, journal = {Microsurgery}, volume = {11}, number = {2}, pages = {140-144}, doi = {10.1002/micr.1920110211}, pmid = {2192225}, issn = {0738-1085}, mesh = {Animals ; Blood Glucose/analysis ; Body Weight ; Diabetes Mellitus, Experimental/*metabolism/surgery ; Drinking ; Eating ; Insulin/blood ; Male ; *Pancreas Transplantation ; Polyuria/metabolism ; Proteinuria/metabolism ; Rats ; Rats, Inbred Lew ; }, abstract = {Thirty-six male Lewis rats rendered diabetic using alloxan received syngeneic pancreaticoduodenal grafts. Seven days prior to and 7, 30, and 90 days posttransplantation, the animals were housed in metabolic cages for periods of 48 hours. During this time, body weight, water intake, food intake, urine output, and fecal output were recorded every 24 hours. Blood sugar, plasma insulin, glucosuria, and proteinuria were determined at 3-month intervals prior to the transplant and at monthly intervals posttransplantation. These parameters were also concurrently recorded for diabetic control rats. Pancreaticoduodenal transplantation produces immediate relief of hyperglycemia, glucosuria, polyuria, polyphasia, and polydypsia, resulting in good health of the animals until the time of sacrifice. A significantly increased insulin level was also recorded. The transplanted animals showed a weight gain reflecting that of a normal growth curve.}, }
@article {pmid2128381, year = {1990}, author = {Ittel, TH and Köppe, BK and Sieberth, HG}, title = {Differential effect of steroids and chloroquine on the intestinal absorption of aluminium and calcium.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {5}, number = {10}, pages = {860-867}, doi = {10.1093/ndt/5.10.860}, pmid = {2128381}, issn = {0931-0509}, mesh = {Aluminum/*pharmacokinetics ; Animals ; Calcium/*pharmacokinetics ; Chloroquine/pharmacology ; *Intestinal Absorption/drug effects ; Male ; Prednisolone/pharmacology ; Rats ; Rats, Inbred Strains ; Vitamin D/metabolism/pharmacology ; }, abstract = {In rats with normal renal function the intestinal absorption of aluminium appears to be partly vitamin D dependent. To further characterise the similarities between the absorption of aluminium and calcium we investigated the effects of dihydroxylated vitamin D metabolites, prednisolone, and chloroquine (CQ) in Sprague-Dawley rats with normal or reduced renal function. The latter agents interfere with lysosomal functions and have been reported to reduce the intestinal absorption of calcium, whereas vitamin D metabolites may stimulate the absorption of both aluminium and calcium. To assess the intestinal absorption of aluminium we monitored urinary aluminium excretion and serum aluminium concentrations following an oral load of 410 mumol aluminium. Calcium absorption was calculated from the differences between an orally administered dose of 45calcium and faecal excretion. In vitamin-D-deficient rats cholecalciferol and calcitriol augmented urinary aluminium excretion to a similar degree subsequent to an oral load whereas 24R,25(OH)2D3 was without an apparent effect. In vitamin-D-replete rats with normal renal function CQ (225 mg/kg i.p.; 3 days) as well as prednisolone (25 mg/kg; 7 days) significantly reduced calcium absorption (% dose) (CQ: 39 +/- 5%, prednisolone: 42 +/- 3%, control: 58 +/- 11%). In contrast neither drug reduced urinary aluminium excretion (CQ: 519 +/- 92, prednisolone: 494 +/- 137, control: 469 +/- 187 nmol/5 days) or the postload increase in serum aluminium following oral exposure. When aluminium was administered intravenously recovery of aluminium was comparable between treatment groups and controls.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid2102504, year = {1990}, author = {Dimitrov, V and Dudunkov, Z and Ralchev, K}, title = {[The results of the formation of a new anal sphincter by using the mm. graciles in acquired anal incontinence].}, journal = {Khirurgiia}, volume = {43}, number = {6}, pages = {11-16}, pmid = {2102504}, issn = {0450-2167}, mesh = {Anal Canal/*surgery ; Caprolactam/analogs &amp; derivatives ; Fecal Incontinence/*surgery ; Humans ; Methods ; Muscles/*transplantation ; Perineum/surgery ; Polymers ; Surgical Mesh ; Suture Techniques ; Tendons/surgery ; }, abstract = {The operative method of Pickrell for shaping a new anal sphincter from mm.graciles is described, emphasizing the refinements which the authors have introduced in it. In mobilizing the muscle, fascial fibers are left on both sides of the vascular-nervous bundle. They prevent the latter from overdistension when the muscle turns around the anal canal. Two arcuate lateral sections are made in the perianal area; this is followed by driving a subcutaneous tunnel, but under the perineal raphe and the anococcygeal ligaments. The two muscles are perianally wound each on 360 degrees, whereby m.gracilis dex. is fixed to tub. ossis ischii sin. and m.gracilis sin. is fixed to tub. ossis ischii dex. Before being fixed, the tendon end is inserted in the subperiosteal bone tunnel. When the tendon of the muscle is shorter, it may successfully be elongated by the explantoplast Ampoxen (applied in 3 patients). A total of 16 patients were treated. The result was good in 15 (93.8 per cent) and unsatisfactory in 1 (6.2 per cent).}, }
@article {pmid2696275, year = {1989}, author = {Shono, T and Nagasaki, A and Goto, S and Ikeda, K}, title = {Experimental free muscle transplantation to the anus using microsurgical technique--a new treatment for anal incontinence.}, journal = {Zeitschrift fur Kinderchirurgie : organ der Deutschen, der Schweizerischen und der Osterreichischen Gesellschaft fur Kinderchirurgie = Surgery in infancy and childhood}, volume = {44}, number = {6}, pages = {352-356}, doi = {10.1055/s-2008-1043272}, pmid = {2696275}, issn = {0174-3082}, mesh = {Anal Canal/physiopathology/*surgery ; Animals ; Dogs ; Electromyography ; Fecal Incontinence/physiopathology/*surgery ; Manometry ; Microsurgery/*methods ; Muscles/*transplantation ; Postoperative Complications/physiopathology ; Suture Techniques ; }, abstract = {Experimental free muscle transplantations to the anus with microneurovascular anastomoses were performed in twenty-one dogs as a model of new treatment for anal incontinence. After undergoing subtotal external sphincterectomy, gracilis muscles were transferred to the anus with microneurovascular anastomoses in Group I (n = 9), without microneurovascular anastomoses in Group II (n = 6), and the muscle transfers were not performed in Group III (n = 6). The mean anal canal pressures decreased to 24.4% of preoperative pressure at one month after subtotal external sphincterectomy. But at six months after muscle transplantation they restored up to 80.7% of preoperative pressure in Group I, 54.7% in Group II and the pressure did not restore in Group III (p less than 0.001 Group I vs Group II and III). Electromyographic study of the graft showed the electrical activity in six of seven dogs (85.7%) in Group I and electrical activity of the graft were not recognized in Group II at six months after transplantation. Histologic study of the graft showed the normal pattern of the muscle fibers in 75-80% of the graft in Group I, and fibrotic degeneration in most areas of the graft in Group II at six months after gracilis muscle transplantation.}, }
@article {pmid2693492, year = {1989}, author = {Odds, FC and Kibbler, CC and Walker, E and Bhamra, A and Prentice, HG and Noone, P}, title = {Carriage of Candida species and C albicans biotypes in patients undergoing chemotherapy or bone marrow transplantation for haematological disease.}, journal = {Journal of clinical pathology}, volume = {42}, number = {12}, pages = {1259-1266}, pmid = {2693492}, issn = {0021-9746}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Antifungal Agents/therapeutic use ; *Bone Marrow Transplantation ; Candida/*isolation &amp; purification ; Candida albicans/isolation &amp; purification ; Feces/microbiology ; Humans ; Leukemia/microbiology/*therapy ; Mouth/microbiology ; }, abstract = {Six hundred and seventy four yeast isolates obtained from routine microbiological screening of 153 patients with haematological disease were identified and Candida albicans isolates biotyped over nine months to determine longitudinal and cross sectional patterns of yeast colonisation. A yeast microflora persisted in many patients despite the routine prophylactic use of oral antifungal agents. Analysis of the yeast species isolated on a cross sectional basis showed that C albicans accounted for 65% of yeasts isolated from the oral cavity but only 45% of the faecal yeast flora. Longitudinal changes in yeast flora occurred significantly more often in faecal samples than in oral samples and significantly less often in sites colonised with C albicans than in sites colonised with other species. No associations were found between the yeasts isolated and the nature of antifungal prophylaxis used, or the extent of a patient's stay in hospital.}, }
@article {pmid2620548, year = {1989}, author = {Imhof, M and Bruch, HP and Pfaff, L and Müller, J}, title = {[A new concept in surgical treatment of anal incontinence].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {60}, number = {12}, pages = {862-5; discussion 865-6}, pmid = {2620548}, issn = {0009-4722}, mesh = {Anal Canal/pathology/*surgery ; Anastomosis, Surgical/methods ; Animals ; Dogs ; Fecal Incontinence/pathology/*surgery ; Ileostomy/methods ; Manometry ; Muscle, Smooth, Vascular/pathology ; Postoperative Complications/pathology ; Saphenous Vein/*transplantation ; Wound Healing ; }, abstract = {A new treatment of anal incontinence has been presented. This method combines the postanal repair of Parks with a sphincteroplasty by autologous large saphenous vein. The vein has no trophic requirements and has a high containing economy. Manometrically, a highly active high pressure zone has been proven. Histologic examinations have shown flubless healing in the intestinal wall of the free vein transplant when prestretched accordingly.}, }
@article {pmid2583017, year = {1989}, author = {Wagner, S and Doss, MO and Wittekind, C and Bäcker, U and Meessen, D and Schmidt, FW}, title = {[Erythrohepatic protoporphyria with rapidly progressing liver cirrhosis].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {114}, number = {47}, pages = {1837-1841}, doi = {10.1055/s-2008-1066836}, pmid = {2583017}, issn = {0012-0472}, mesh = {Cholestyramine Resin/therapeutic use ; Humans ; Liver Cirrhosis/complications/drug therapy/*etiology/surgery ; Liver Diseases/*complications ; Liver Transplantation ; Male ; Middle Aged ; Multiple Organ Failure/etiology ; Porphyrias/blood/*complications ; Porphyrins/*analysis ; Protoporphyrins/*analysis/blood ; Sepsis/etiology ; Ursodeoxycholic Acid/therapeutic use ; }, abstract = {A 49-year-old man, known to have had an increased light sensitivity since childhood, was admitted to hospital because of jaundice. Biochemical and morphological examination revealed cirrhosis of the liver with cholestasis. There was a 70-fold increase of protoporphyrin content in the erythrocytes, increased fecal protoporphyrin excretion as well as secondary coproporphyrinuria. Despite symptomatic treatment with ursodeoxycholic acid and cholestyramine hepatic failure ensued for which orthotopic liver transplantation was performed five months after the diagnosis had been made. The patient died two months later of treatment-resistant septicaemia and multiorgan failure. This case demonstrates the need for annual monitoring of liver functions and porphyrin parameters to ensure earliest possible diagnosis of hepatic involvement in erythrohepatic protoporphyria.}, }
@article {pmid2510515, year = {1989}, author = {Wolf, JE and Liu, HH and Rabinowitz, LG}, title = {Ecthyma gangrenosum in the absence of Pseudomonas bacteremia in a bone marrow transplant recipient.}, journal = {The American journal of medicine}, volume = {87}, number = {5}, pages = {595-597}, doi = {10.1016/s0002-9343(89)80624-2}, pmid = {2510515}, issn = {0002-9343}, mesh = {Adult ; *Bone Marrow Transplantation ; Clostridium/isolation &amp; purification ; Ecthyma/*microbiology/pathology ; Feces/microbiology ; Gangrene ; Humans ; Male ; Pseudomonas aeruginosa/isolation &amp; purification ; Staphylococcus aureus/isolation &amp; purification ; }, }
@article {pmid2686547, year = {1989}, author = {Giuliano, M and Pantosti, A and Gentile, G and Venditti, M and Arcese, W and Martino, P}, title = {Effects on oral and intestinal microfloras of norfloxacin and pefloxacin for selective decontamination in bone marrow transplant patients.}, journal = {Antimicrobial agents and chemotherapy}, volume = {33}, number = {10}, pages = {1709-1713}, pmid = {2686547}, issn = {0066-4804}, mesh = {Adult ; *Bone Marrow Transplantation ; Drug Resistance, Microbial ; Feces/microbiology ; Female ; Humans ; Immunosuppression Therapy ; Intestines/drug effects/*microbiology ; Leukemia/therapy ; Male ; Mouth/drug effects/*microbiology ; Norfloxacin/*pharmacology ; Pefloxacin/*pharmacology ; Staphylococcus/drug effects ; Whole-Body Irradiation ; }, abstract = {We monitored the modifications of oral and intestinal microfloras of 10 allogeneic bone marrow recipients who received randomly either norfloxacin or pefloxacin (400 mg three times a day) as selective decontamination for infection prevention. After 1 week of treatment, in all patients members of the family Enterobacteriaceae were no longer detectable and in all but one pefloxacin-treated patient enterococci were also eliminated in the intestine. The anaerobic flora was not affected, with the exception of Bacteroides spp., markedly reduced after treatment with pefloxacin. In most patients the most striking effect was the increase in staphylococcal counts. These strains were found to be resistant to both quinolones in the study. Less consistent changes were observed in oral flora. No relevant difference could be demonstrated between the two regimens on bacterial counts either in feces or in saliva. This study shows the efficacy of both quinolones in eradicating gram-negative bacilli in the alimentary tract of bone marrow transplant patients; however, the finding of the overgrowth of resistant gram-positive organisms during treatment with these agents deserves further evaluation.}, }
@article {pmid2799076, year = {1989}, author = {Mostofa, M and McKellar, QA}, title = {Effect of an antimuscarinic drug on the plasma pepsinogen activity of sheep infected with Ostertagia circumcincta.}, journal = {Research in veterinary science}, volume = {47}, number = {2}, pages = {208-211}, pmid = {2799076}, issn = {0034-5288}, mesh = {Animals ; Atropine/administration &amp; dosage/*pharmacology ; Feces/parasitology ; Injections, Subcutaneous/veterinary ; Ivermectin/therapeutic use ; Ostertagiasis/blood/drug therapy/*veterinary ; Parasite Egg Count/veterinary ; Pepsinogens/*blood ; Sheep ; Sheep Diseases/*blood/drug therapy ; Trichostrongyloidiasis/*veterinary ; }, abstract = {The antimuscarinic drug atropine caused a marked fall in plasma pepsinogen values of sheep with burdens of Ostertagia circumcincta and this response was greater in animals which had higher plasma pepsinogen values before administration of the drug. The response was shown to occur whether the elevated plasma pepsinogen values were a consequence of a larval infection in previously naive or exposed animals or of adult parasites directly transplanted into the abomasum of naive lambs.}, }
@article {pmid2769016, year = {1989}, author = {Barton, CH and Vaziri, ND and Mina-Araghi, S and Crosby, S and Seo, MI}, title = {Effects of cyclosporine on magnesium metabolism in rats.}, journal = {The Journal of laboratory and clinical medicine}, volume = {114}, number = {3}, pages = {232-236}, pmid = {2769016}, issn = {0022-2143}, mesh = {Animals ; Creatinine/blood ; Cyclosporins/*pharmacology ; Diuresis/drug effects ; Intestinal Absorption/drug effects ; Kidney/drug effects/metabolism ; Magnesium/blood/*metabolism/urine ; Rats ; Rats, Inbred Strains ; Reference Values ; }, abstract = {Earlier studies have revealed hypomagnesemia with cyclosporine treatment in renal and bone marrow transplant recipients. The present study was designed to investigate the possible effect of cyclosporine on Mg metabolism in normal rats. Sprague-Dawley rats were randomized into the cyclosporine group, which was given 15 mg/kg/day cyclosporine by gastric gavage, and the control group, which received the vehicle alone. Food intake, body weight, serum concentration, urinary excretion, fecal excretion, and tissue content of Mg were determined weekly for 3 weeks. In addition, intestinal absorption of Mg was determined by using in vivo perfusion. Serum Mg concentration fell significantly after 1 week of cyclosporine treatment and remained low throughout the observation period. This was associated with reduced food intake and renal Mg conservation during the first week but normal food intake and severe renal Mg wasting thereafter. In vivo perfusion studies performed at 1 and 3 weeks showed no significant difference in intestinal absorption of Mg between the two groups, thereby excluding intestinal malabsorption as a possible culprit. Likewise, fecal Mg excretion showed no significant difference in the two groups. It was surprising that tissue Mg content (in muscle, liver, and kidney) was increased in the cyclosporine-treated group at 3 weeks. We conclude that cyclosporine administration in rats leads to a fall in serum Mg concentration primarily as a result of renal Mg wasting and possibly as a result of a shift of Mg to the tissue compartments with no discernible effect on gastrointestinal handling of Mg.}, }
@article {pmid2668434, year = {1989}, author = {Roncoroni, AJ and Gomez, MA and Mera, J and Cagnoni, P and Michel, MD}, title = {Cryptosporidium infection in renal transplant patients.}, journal = {The Journal of infectious diseases}, volume = {160}, number = {3}, pages = {559}, doi = {10.1093/infdis/160.3.559}, pmid = {2668434}, issn = {0022-1899}, mesh = {Animals ; Coccidia/*isolation &amp; purification ; Cryptosporidiosis/complications/*diagnosis ; Cryptosporidium/*isolation &amp; purification ; Diarrhea/etiology ; Feces/microbiology ; Humans ; *Kidney Transplantation ; }, }
@article {pmid2673459, year = {1989}, author = {Chastagner, P and Hartmann, O and Tancrede, C and Kalifa, C and Patte, C and Flamant, F and Lemerle, J}, title = {Role of parenteral antibiotherapy in gastrointestinal tract flora suppression. A study in children treated with high-dose chemotherapy and autologous bone marrow transplantation.}, journal = {Bone marrow transplantation}, volume = {4}, number = {4}, pages = {393-398}, pmid = {2673459}, issn = {0268-3369}, mesh = {Adolescent ; Agranulocytosis/drug therapy/*therapy ; *Bone Marrow Transplantation ; Cefotaxime/administration &amp; dosage/therapeutic use ; Child ; Child, Preschool ; Digestive System/*immunology ; Dose-Response Relationship, Drug ; Drug Combinations/administration &amp; dosage/therapeutic use ; Feces/microbiology ; Female ; Gentamicins/administration &amp; dosage/therapeutic use ; Gram-Positive Bacteria/isolation &amp; purification ; Humans ; Infusions, Parenteral/*standards ; Male ; Mezlocillin/administration &amp; dosage/therapeutic use ; Moxalactam/administration &amp; dosage/therapeutic use ; Sulfamethizole/administration &amp; dosage/therapeutic use ; Suppression, Genetic ; Tobramycin/administration &amp; dosage/therapeutic use ; Transplantation, Autologous ; Trimethoprim/administration &amp; dosage/therapeutic use ; }, abstract = {In order to determine the effect of parenteral antibiotherapy on the fecal flora in patients with profound and prolonged granulocytopenia, we initiated a prospective study of 62 cases of autologous bone marrow transplantation following high-dose chemotherapy. All patients were children from 2 to 18 years old, isolated in a protective environment, receiving a diet low in viable microbial content but no oral non-absorbable prophylactic antibiotics to decontaminate the gastrointestinal tract. Bacteriological analysis of fecal flora was conducted at least once a week before and during parenteral antibiotherapy, administered at the first greater than 38 degrees C febrile episode in these granulocytopenic patients (granulocyte count less than 0.5 X 10(9)/l). The 58 evaluable patients fell into three groups with regard to the systemic antibiotherapy: group A (n = 16): moxalactam + mezlocillin; group B (n = 15): moxalactam + tobramycin; and group C (n = 27): cefotaxime plus gentamicin. Fecal flora suppression was observed in 51/58 cases (88%) (group A: 15/16, group B: 13/15, group C: 23/27). It always occurred within 5 days of initiating parenteral antibiotherapy and persisted in 88% of the 51 patients over the whole period of systemic antibiotherapy. During the latter, fecal recolonization was observed in seven cases (12%), always by Enterobacteriaceae sensitive to the prescribed systemic antibiotherapy, never responsible for septicemia. Since parenteral antibiotherapy alone was able to suppress the gastrointestinal tract flora, the effects of this treatment should be considered in all trials of digestive tract decontamination.}, }
@article {pmid2656363, year = {1989}, author = {Bloomer, JR and Weimer, MK and Bossenmaier, IC and Snover, DC and Payne, WD and Ascher, NL}, title = {Liver transplantation in a patient with protoporphyria.}, journal = {Gastroenterology}, volume = {97}, number = {1}, pages = {188-194}, doi = {10.1016/0016-5085(89)91434-0}, pmid = {2656363}, issn = {0016-5085}, support = {DK 26466/DK/NIDDK NIH HHS/United States ; DK 34931/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Biopsy ; Exchange Transfusion, Whole Blood ; Female ; Follow-Up Studies ; Humans ; Liver/analysis/pathology ; Liver Diseases/*surgery ; *Liver Transplantation ; Porphyrias/*surgery ; Protoporphyrins/blood ; }, abstract = {A 38-yr-old woman with liver disease due to protoporphyria underwent orthotopic liver transplantation. The resected liver was cirrhotic and contained a massive amount of protoporphyrin, with numerous birefringent pigment deposits. Transplantation was accomplished without difficulty following blood volume exchange to reduce the blood protoporphyrin level. Sequential biopsy specimens obtained through the 13th month after transplantation showed no accumulation of protoporphyrin pigment deposits in the new liver. Portal inflammation observed in the liver biopsy specimen at 6 mo after transplantation resolved spontaneously. Erythrocyte and serum protoporphyrin levels returned to values similar to those in the pretransplantation period when the patient had normal hepatic function; the fecal level was lower. Thus orthotopic liver transplantation can be successfully done in patients with protoporphyria who have severe liver disease. Prolonged follow-up is needed to determine the ultimate outcome, however, as the new liver remains susceptible to protoporphyrin-induced damage.}, }
@article {pmid2598735, year = {1989}, author = {Ge, LZ}, title = {[Anal sphincter reconstruction by interposition of an ileo-colonic segment and transposition of musculi glutaeus maximus bundles after resection of anorectal carcinoma].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {27}, number = {7}, pages = {387-9, 443}, pmid = {2598735}, issn = {0529-5815}, mesh = {Adult ; Anal Canal/*surgery ; Anus Neoplasms/surgery ; Colostomy/*methods ; Humans ; Ileum/*transplantation ; Middle Aged ; Rectal Neoplasms/surgery ; *Surgical Flaps ; }, abstract = {From April 1983 to July 1987, 33 anorectal cancer patients were treated with segmental ileocolonic interposition and transposition of muscular bundles of musculi glutaeus maximus to reconstruct of anal sphincters after abdominoperineal resection of the carcinoma (Miles' operation). All patients were followed up for a half up to 3.5 years. The function of reconstructed anal sphincters was evaluated by fecal evacuating ability, by pressure measurement of the reconstructed internal and external sphincters, and by X-ray observation. The function was rated as good to perfect in all of the patients.}, }
@article {pmid2532026, year = {1989}, author = {Rosenberg, PH and Geiss, AC and Nelson, RL and Tortolani, AJ}, title = {Model of intestinal continence using an implantable pulse generator and a myoprosthetic sphincter.}, journal = {ASAIO transactions}, volume = {35}, number = {3}, pages = {222-225}, doi = {10.1097/00002480-198907000-00014}, pmid = {2532026}, issn = {0889-7190}, mesh = {Abdominal Muscles/*transplantation ; Animals ; Dogs ; Electric Stimulation Therapy/*instrumentation ; Electrodes, Implanted ; Fecal Incontinence/physiopathology/*prevention &amp; control ; Gastrointestinal Motility/physiology ; Ileostomy/*instrumentation ; *Polytetrafluoroethylene ; }, abstract = {Past attempts at artificial continence using a wide range of surgical procedures and devices have met with only limited success because of excessive rates of infection, rejection, incomplete continence, and technical difficulty. Presented here is a model of artificial continence using a lumen-occluding Teflon loop powered by the rectus abdominus muscle and activated by an implantable pulse generator. Eight female mongrel dogs underwent laparotomy with creation of a Brooke ileostomy and insertion of a hand-tooled Teflon band around the ileum. The free ends of the loop were sutured, under tension, to the posterior rectus sheath creating extrinsic compression of the bowel by the tightened loop. After denervation of the rectus, stimulating electrodes were implanted and connected to a transcutaneously activated pulse generator (Medtronic SE-4). Stimulation caused contraction of the muscle segment. As the free ends of the prosthetic sling approach each other, the occlusive band loosens, resulting in free drainage of intestinal contents and reduction in intraluminal pressure of the proximal ileum. Withdrawal of current allows for relaxation and return of the muscle to its resting length; this reoccludes the bowel. At 2 weeks, all dogs were continent to solid matter and all but two were continent to liquids. Two dogs developed wound infections requiring drainage. Signal attenuation across the skin resulted in total uncontrollable continence in two dogs because of an inability to transfer sufficient current to the muscle. Direct probe stimulation by an external pulse generator resulted in drainage in these dogs. Necropsy showed no evidence of bowel ischemia in any of the specimens examined at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid2668743, year = {1989}, author = {Mühlbauer, B and Huber, S and Hoppe, JE and Stier, B and Dopfer, R and Niethammer, D}, title = {[Systemic salmonella infections in chemotherapy in 2 children with acute lymphoblastic leukemia].}, journal = {Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde}, volume = {137}, number = {6}, pages = {337-340}, pmid = {2668743}, issn = {0026-9298}, mesh = {Adolescent ; Antineoplastic Agents/*therapeutic use ; *Bone Marrow Transplantation ; Carrier State/diagnosis ; Child, Preschool ; Combined Modality Therapy ; Feces/microbiology ; Femoral Fractures/diagnosis ; Fractures, Spontaneous/diagnosis ; Humans ; Male ; Opportunistic Infections/*diagnosis ; Osteomyelitis/diagnosis ; Postoperative Complications/*diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy ; Salmonella Infections/*diagnosis ; Salmonella typhimurium/isolation &amp; purification ; Sepsis/*diagnosis ; }, abstract = {A 15 year old patient with acute lymphoblastic leukemia, previously diagnosed as being a salmonella carrier, developed S. typhimurium sepsis after allogeneic bone marrow transplantation, in spite of pretreatment with chloramphenicol. Clinical improvement and termination of salmonella excretion were achieved by treatment with multiple antibiotics. Another patient with acute lymphoblastic leukemia, a 3 year old boy not previously identified as a salmonella carrier, also developed sepsis and osteomyelitis, together with pathological fractures during chemotherapy. Chloramphenicol, administered after isolation of S. typhimurium from blood cultures, led to resolution of the bony defects, complete recovery, and cessation of salmonella excretion. Selective cultures for salmonellae seem indicated in patients with malignant diseases, prior to chemotherapy.}, }
@article {pmid2728007, year = {1989}, author = {Marchok, AC and Fleming, GS and Tomkins, BA and Griest, WH}, title = {[3H]benzo[a]pyrene utilization in rats following tracheal implant exposure.}, journal = {Toxicology}, volume = {56}, number = {1}, pages = {63-77}, doi = {10.1016/0300-483x(89)90212-6}, pmid = {2728007}, issn = {0300-483X}, support = {CA 543857/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Autoradiography ; Benzo(a)pyrene/administration &amp; dosage/pharmacokinetics/*toxicity ; Female ; Gels ; Germ-Free Life ; Rats ; Rats, Inbred F344 ; Tissue Distribution ; Trachea/*drug effects/transplantation ; Tritium ; }, abstract = {Open-ended rat tracheal implants (OETI) were exposed to 40 micrograms [3H]benzo[a]pyrene (B[a]P)-gelatin pellets and the 3H activity in the OETI, the host's tissues and excretia was determined 3-96 h after insertion of the pellets. The radioactivity in the OETI reached near peak activity by 3 h, and decreased almost 10-fold by 24 h. Most of the activity was associated with parent B[a]P throughout the 95 h. The 3H activity in the surrounding tissue also was mostly associated with B[a]P, but the 3H activity in the liver, kidney, blood and urine was mostly associated with water-soluble plus conjugated metabolites. In the feces, 68% of the 3H activity was in B[a]P at 3 h, but mostly organic as well as water-soluble plus conjugated metabolites were extracted from it throughout the remaining 96 h. Forty-eight hours after insertion of the B[a]P pellets, the feces contained almost 16% of the total 3H activity. Pre-exposure of the OETI to B[a]P for 4 days before insertion of the [3H]B[a]P pellets stimulated metabolism of B[a]P in the tracheas approximately 2-fold, but had no significant effect on the host tissues.}, }
@article {pmid2526329, year = {1989}, author = {Au, JL and Gunnarsson, LC}, title = {Absorption of 5'-deoxy-5-fluorouridine from colon.}, journal = {Pharmaceutical research}, volume = {6}, number = {4}, pages = {323-327}, pmid = {2526329}, issn = {0724-8741}, support = {CA-37110/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacokinetics ; Biological Availability ; Colon/*metabolism ; Feces/analysis ; Female ; Floxuridine/*pharmacokinetics ; *Intestinal Absorption ; Rats ; Tissue Distribution ; }, abstract = {Rectally administered 5'-deoxy-5-fluorouridine (dFUR) is active against transplanted dimethylhydrazine-induced colon tumor in rats. This study investigated the disposition of dFUR in normal non-tumor-bearing rats after rectal administration (350 or 700 mg/kg). An intravenous (iv) bolus injection of [5'-3H]dFUR (28.2 muCi, 0.43 micrograms) was given 5 min after the rectal dose (700 mg/kg) to determine the dFUR clearance (CL). Blood and fecal samples were analyzed by high-pressure liquid chromatography and liquid scintillation. After the iv tracer dose, the CL was 19 ml/min/kg and the terminal half-life was 50 min. After a 700-mg/kg rectal dose, the terminal half-life was 430 min, the bioavailability was 30%, and the fraction of the dose recovered in 24-hr feces was 34%. After a 350-mg/kg dose, absorption was apparently not completed at 12 hr, as indicated by a lack of decline in blood concentration. The bioavailability of the 350-mg/kg dose exceeded 16%. The absorption of dFUR (700 mg/kg) from the colon was analyzed by the Loo-Riegelman method: the absorption half-life was 550 min. The terminal half-life after the rectal dose was much slower than that after the iv tracer dose but similar to the absorption half-life. These data indicate that dFUR was absorbed from the colon, that the absorption process was the rate-limiting step of its disposition after rectal administration, and that the slow absorption gave a sustained drug concentration in blood.}, }
@article {pmid2669709, year = {1989}, author = {Blakey, JL and Barnes, GL and Bishop, RF and Ekert, H}, title = {Infectious diarrhea in children undergoing bone-marrow transplantation.}, journal = {Australian and New Zealand journal of medicine}, volume = {19}, number = {1}, pages = {31-36}, doi = {10.1111/j.1445-5994.1989.tb01670.x}, pmid = {2669709}, issn = {0004-8291}, mesh = {Adolescent ; *Bone Marrow Transplantation ; Child ; Child, Preschool ; Diarrhea/*etiology ; *Enterobacteriaceae Infections/diagnosis ; Feces/analysis ; Female ; Humans ; Infant ; Male ; Prospective Studies ; }, abstract = {Fecal flora of 12 children undergoing bone-marrow transplantation was monitored prospectively using comprehensive microbiological techniques. Diarrhea developed at least once in ten of the 12 children (83%), and a total of 24 episodes were recorded. Recognised gut pathogens were isolated from 11/21 (52%) diarrheal episodes where fecal specimens were obtained. Enteric pathogens identified included viral pathogens in 19% (rotaviruses, 'enteric' adenoviruses), parasites in 19% (cryptosporidium, Giardia lamblia) and cytotoxic C. difficile (14%). Excretion of clostridial species (including cytotoxin negative C. difficile, C. innocuum) occurred in 90% of diarrheal episodes when no enteric pathogen was identified. These results suggest that infection is often responsible for diarrhea associated with bone-marrow transplantation. Prophylaxis against enteric infection might reduce the morbidity and mortality associated with severe diarrhea in bone-marrow transplanted children.}, }
@article {pmid2763603, year = {1989}, author = {Gögler, H and Meckes, P}, title = {[Peritonitis, septic shock and endotoxin--an animal experiment study].}, journal = {Zeitschrift fur experimentelle Chirurgie, Transplantation, und kunstliche Organe : Organ der Sektion Experimentelle Chirurgie der Gesellschaft fur Chirurgie der DDR}, volume = {22}, number = {3}, pages = {159-167}, pmid = {2763603}, issn = {0232-7295}, mesh = {Animals ; Ascitic Fluid/microbiology ; Bacteria/isolation &amp; purification ; Bacterial Infections/*microbiology ; Dogs ; Endotoxins/*blood ; Feces/microbiology ; Intestinal Perforation/microbiology ; Limulus Test ; Peritonitis/*microbiology ; Shock, Septic/*microbiology ; }, abstract = {Fecal peritonitis was produced by a sphincter-system leading to intestinal perforation. In 10 beagle dogs endotoxin was measured with the Limulus test. There was a correlation between endotoxin appearance and microbiological findings in the peritoneal cavity and in the blood. Endotoxinaemia correlated with the clinical severity of peritonitis.}, }
@article {pmid2711722, year = {1989}, author = {Wesslau, C and Jung, K and Fritsch, W and Kreuschner, H}, title = {[A model of a rat cage for the collection of urine free of fecal matter].}, journal = {Zeitschrift fur experimentelle Chirurgie, Transplantation, und kunstliche Organe : Organ der Sektion Experimentelle Chirurgie der Gesellschaft fur Chirurgie der DDR}, volume = {22}, number = {1}, pages = {59-61}, pmid = {2711722}, issn = {0232-7295}, mesh = {Animals ; Feces ; *Housing, Animal ; Rats/*urine ; Specimen Handling/methods/standards/*veterinary ; }, abstract = {A cage for total separation of feces and urine in the awake rat is presented. Construction and function are described in detail. Two important indications (investigation of the urinary enzyme activity, and determination of the endogenous creatinine clearance) are denominated.}, }
@article {pmid2577628, year = {1989}, author = {Bruch, HP}, title = {[The continent stoma].}, journal = {Langenbecks Archiv fur Chirurgie. Supplement II, Verhandlungen der Deutschen Gesellschaft fur Chirurgie. Deutsche Gesellschaft fur Chirurgie. Kongress}, volume = {}, number = {}, pages = {729-733}, pmid = {2577628}, issn = {0173-0541}, mesh = {Colostomy/*instrumentation ; Fecal Incontinence/*prevention &amp; control ; Humans ; Muscles/*transplantation ; Postoperative Complications/*prevention &amp; control ; *Prostheses and Implants ; Rectal Neoplasms/*surgery ; Suture Techniques ; }, abstract = {Stomatic continence is not comparable to the complicated system of the anorectal organ. Therefore, the definition of continence is ability to arbitrarily determine defecation but with some restriction. It further means the nonreliance on a stoma bag for the intervals between defecation. Continence is achieved by special diet, irrigation, laxatives and clysters. It can be supported by passive and active implants as well as surgical techniques which use smooth and striated muscle functions to imitate, to a certain extent, the muscular components of the anorectal organ.}, }
@article {pmid2480310, year = {1989}, author = {Wonitzki, C and Hoffmann, FA}, title = {Bacteriological findings in patients with bone marrow transplantation (Karl Marx University Leipzig, 1985-1987).}, journal = {Folia haematologica (Leipzig, Germany : 1928)}, volume = {116}, number = {3-4}, pages = {569-576}, pmid = {2480310}, issn = {0323-4347}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacteria/*isolation &amp; purification ; Bacterial Infections/etiology/*microbiology/prevention &amp; control ; Blood/microbiology ; Bone Marrow Transplantation/*adverse effects ; Decontamination ; Feces/microbiology ; Humans ; Intestines/microbiology ; Microbial Sensitivity Tests ; Mucous Membrane/microbiology ; Pharynx/microbiology ; Pseudomonas aeruginosa/isolation &amp; purification ; Staphylococcus/isolation &amp; purification ; }, abstract = {The results of the bacteriological surveillance cultures for 26 patients with bone marrow transplantation (Karl Marx University Leipzig, G.D.R., 1985-1987) are presented. 5.9% of all surveillance cultures contained facultatively pathogenic germs (with Pseudomonas aeruginosa as the most frequent representative, which was the reason of a sepsis in two patients). Coagulasenegative Staphylococci and other germs with an obscure pathogenicity were isolated upon a large scale, especially from the mucous membrane regions. There are hints, that above all special strains of coagulasenegative Staphylococci "colonize" the patient's body (also for longer periods) and turn into the blood too. During the total decontamination intestinal anaerobic flora is absent. After closing of total decontamination Clostridium perfringens is the first detectable anaerobic species. During the selective decontamination systemic applications of antibiotics are able to obliterate anaerobic findings for certain periods. Recommendations for an effective arrangement of the surveillance cultures of bone marrow transplantation patients are given.}, }
@article {pmid2474913, year = {1989}, author = {Fortýn, K and Hruban, V and Hradecký, J and Tichý, J and Dvorák, P and Horák, V}, title = {Experimental devascularization (devitalization) of the rectum and sigmoideum.}, journal = {Zeitschrift fur experimentelle Chirurgie, Transplantation, und kunstliche Organe : Organ der Sektion Experimentelle Chirurgie der Gesellschaft fur Chirurgie der DDR}, volume = {22}, number = {3}, pages = {173-179}, pmid = {2474913}, issn = {0232-7295}, mesh = {Anal Canal/surgery ; Anastomosis, Surgical/methods ; Animals ; Arteries/surgery ; Colon, Sigmoid/*blood supply/pathology ; Colostomy/*methods ; Fecal Incontinence/*prevention &amp; control ; Male ; Necrosis ; Palliative Care ; Postoperative Complications/*prevention &amp; control ; Rectal Neoplasms/surgery ; Rectum/*blood supply/pathology ; Swine ; }, abstract = {In 6 laboratory pigs, devascularization (devitalization) of the rectum and the adjacent part of the sigmoideum was carried out by the vasa rectalia cranialia et media ligatures with simultaneous aboral closure of the rectum at the base of the lesser pelvis and oral closure at the borderline between the rectum and the sigmoideum. The devascularized rectum was not removed but left in situ. Terminal colostomy was established. Laparotomic revision was carried out after 12 weeks, colostomy was removed and continuity of the intestine was reestablished by insertion anastomosis, by suture of the end of the colon to the anal mucosa and skin. In further two pigs, devascularization of the rectosigmoideum was carried out with colostomy and reconstruction was carried out after 12 weeks by procto-sigmoideo-anastomosis. In another 2 animals, devascularization was carried out on the lower part of the sigmoideum and continuity was immediately renewed by end-to-side sigmoideo-sigmo-ideoanastomosis. All revisions indicated that the devascularized necrotic segment shrank to form a minute fibrous tissue residue, anastomosis was patent and continence was retained for colo-proctoanastomosis. The described techniques are technically simple and could be employed as palliative surgical methods for inoperable tumours in the region of the rectum and lower part of the sigmoideum.}, }
@article {pmid3193521, year = {1988}, author = {Kim, KS and Susskind, MR and King, LR}, title = {Ileocecal ureterosigmoidostomy: an alternative to conventional ureterosigmoidostomy.}, journal = {The Journal of urology}, volume = {140}, number = {6}, pages = {1494-1498}, doi = {10.1016/s0022-5347(17)42083-0}, pmid = {3193521}, issn = {0022-5347}, mesh = {Adolescent ; Bladder Exstrophy/surgery ; Child ; Colon, Sigmoid/*surgery ; Enterostomy/methods ; Epispadias/surgery ; Female ; Humans ; Ileocecal Valve/*transplantation ; Infant ; Male ; Postoperative Complications/etiology ; Urinary Diversion/*methods ; Urinary Tract Infections/etiology ; }, abstract = {We describe a 1-stage procedure that involves use of the ileocecal segment as an intervening urine conduit to the large bowel to achieve a continent diversion. The ureters are anastomosed end to end to the terminal ileum that is intussuscepted into the cecum. The cecum then is joined to the lower sigmoid by an end-to-side anastomosis. Mixed urine and feces are eliminated through the rectum. The results in 5 patients with exstrophy and 1 with epispadias between 5 months and 13 years old are reported. Ureteral reflux was not observed. Urinary tract infection developed in 2 patients. Ileocecal ureterosigmoidostomy is a reasonable alternative to intact ureterosigmoidostomy that may reduce the risk of development of cancer.}, }
@article {pmid3145855, year = {1988}, author = {Daw, MA and Munnelly, P and McCann, SR and Daly, PA and Falkiner, FR and Keane, CT}, title = {Value of surveillance cultures in the management of neutropenic patients.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {7}, number = {6}, pages = {742-747}, pmid = {3145855}, issn = {0934-9723}, mesh = {Adolescent ; Adult ; Agranulocytosis/*microbiology ; Bacterial Infections/etiology ; Bone Marrow Transplantation ; Enterobacteriaceae/*isolation &amp; purification ; Feces/microbiology ; Humans ; Middle Aged ; Neutropenia/complications/*microbiology ; Pseudomonas aeruginosa/*isolation &amp; purification ; }, abstract = {To assess whether bacteriological surveillance cultures can be used to predict infection in neutropenic patients, cultures were performed during the period of neutropenia of nose, throat and urine specimens collected once weekly and faeces specimens collected twice weekly. Seventy-six consecutively observed patients undergoing chemotherapy for haematological or non-haematological diseases were investigated. Severe infection including septicaemia, lower respiratory tract infection, anorectal lesion and urinary tract infection occurred in 32 patients. Enterobacter cloacae, Escherichia coli and Pseudomonas aeruginosa were the organisms most commonly involved. In the majority of cases of septicaemia the organisms were isolated from the faeces, often in pure culture, prior to the onset of septicaemia. Most of the isolates of Enterobacter cloacae were resistant to the empiric antibiotic therapy used in the unit and were able to colonise multiple sites, presumably increasing the risk of subsequent infection. Faecal culture is the most useful approach in bacteriological surveillance in neutropenic patients.}, }
@article {pmid3054334, year = {1988}, author = {Rotstein, C and Higby, D and Killion, K and Powell, E}, title = {Relationship of surveillance cultures to bacteremia and fungemia in bone marrow transplant recipients with Hickman or Broviac catheters.}, journal = {Journal of surgical oncology}, volume = {39}, number = {3}, pages = {154-158}, doi = {10.1002/jso.2930390304}, pmid = {3054334}, issn = {0022-4790}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/therapeutic use ; *Bone Marrow Transplantation ; Catheters, Indwelling/*adverse effects ; Child ; Child, Preschool ; False Positive Reactions ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Mycoses/*prevention &amp; control ; Pharynx/microbiology ; Sepsis/*prevention &amp; control ; Skin/microbiology ; Staphylococcus/isolation &amp; purification ; }, abstract = {A total of 64 episodes of bacteremia and fungemia were documented in 25 allogeneic bone marrow transplant recipients. Coagulase-negative staphylococci were the most common pathogens recovered, with 34 of the 39 isolated being methicillin resistant. Streptococcus viridans (11 episodes), diphtheroids (5 episodes), and Pseudomonas aeruginosa (4 episodes) accounted for the majority of the other pathogens causing bacteremia. Six episodes of fungemia were also seen. Coagulase-negative staphylococci were demonstrated in 31 of 36 (86%) throat cultures, 25 of 35 (71%) stool cultures, and 6 of 7 (86%) Hickman or Broviac catheter exit site surveillance cultures prior to the development of bacteremia caused by these organisms. Throat surveillance cultures positive for S. viridans also showed a correlation (88%) with subsequent S. viridans bacteremia. However, surveillance cultures for aerobic gram-negative bacilli, diphtheroids, and fungi did not correlate with subsequent septicemia. Organisms isolated in throat surveillance cultures correlated with subsequent bacteremia caused by these organisms in only 15% of all the cultures taken, while only 14% of stool cultures predicted bacteremia. The utility of surveillance cultures is limited because of low cost-effectiveness and a high rate of false-positive results.}, }
@article {pmid3168662, year = {1988}, author = {Yoshioka, K and Keighley, MR}, title = {Clinical and manometric assessment of gracilis muscle transplant for fecal incontinence.}, journal = {Diseases of the colon and rectum}, volume = {31}, number = {10}, pages = {767-769}, doi = {10.1007/BF02560102}, pmid = {3168662}, issn = {0012-3706}, mesh = {Adult ; Anal Canal/physiopathology ; Fecal Incontinence/physiopathology/*surgery ; Female ; Humans ; Male ; Manometry ; Methods ; Middle Aged ; Muscles/*transplantation ; Surgical Wound Infection/etiology ; Thigh ; }, abstract = {Six cases of gracilis muscle transplant for fecal incontinence are reported. The causes of fecal incontinence included previous anal operation, idiopathic incontinence, and rectal prolapse. All patients had had a previous operation for fecal incontinence. Postoperative sepsis developed at the operative site in five patients despite a defunctioning colostomy in two. Functional results of the operation were poor in all patients and a colostomy has now been raised in all cases. The operation was not associated with any objective improvement in resting or voluntary component pressure.}, }
@article {pmid3294082, year = {1988}, author = {Samuel, D and Boboc, B and Bernuau, J and Bismuth, H and Benhamou, JP}, title = {Liver transplantation for protoporphyria. Evidence for the predominant role of the erythropoietic tissue in protoporphyrin overproduction.}, journal = {Gastroenterology}, volume = {95}, number = {3}, pages = {816-819}, pmid = {3294082}, issn = {0016-5085}, mesh = {Adult ; Erythrocytes/*metabolism ; Feces/analysis ; Female ; Humans ; Liver/metabolism ; Liver Cirrhosis/etiology/*surgery ; *Liver Transplantation ; Porphyrias/blood/genetics/metabolism/*surgery ; Porphyrins/*biosynthesis ; Protoporphyrins/analysis/*biosynthesis/blood ; }, abstract = {Protoporphyria is an inherited disorder of heme biosynthesis characterized by an overproduction of protoporphyrin in the erythropoietic and hepatic tissues, the relative contribution of which in the metabolic disorder has not been directly quantitated. Excess protoporphyrin is eliminated solely by the liver into the bile and feces. We describe the case of a patient with protoporphyria complicated by severe cirrhosis in whom liver transplantation was performed and resulted in almost complete disappearance of skin photosensitivity manifestations and reduction in the level of protoporphyrin in erythrocytes. However, the level of protoporphyrin in feces was not markedly different before and after liver transplantation, which suggests that overproduction of protoporphyrin was unchanged. These findings are consistent with the view that the diseased liver and ensuing low hepatic clearance of protoporphyrin contributed to accumulation of protoporphyrin in the body and that, at least in this patient, the role of the hepatic tissue in the overproduction of protoporphyrin was small in comparison with that of the erythropoietic tissue.}, }
@article {pmid3047929, year = {1988}, author = {Polson, RJ and Lim, CK and Rolles, K and Calne, RY and Williams, R}, title = {The effect of liver transplantation in a 13-year-old boy with erythropoietic protoporphyria.}, journal = {Transplantation}, volume = {46}, number = {3}, pages = {386-389}, doi = {10.1097/00007890-198809000-00010}, pmid = {3047929}, issn = {0041-1337}, mesh = {Adolescent ; Erythropoiesis ; Female ; Humans ; Liver Diseases/*therapy ; *Liver Transplantation ; Male ; Photosensitivity Disorders/therapy ; Porphyrias/*therapy ; Protoporphyrins/blood ; }, abstract = {A 13-year-old boy who had had recurrent photosensitive skin reactions due to erythropoietic protoporphyria from 18 months of age, suddenly developed rapidly progressive hepatic failure with increasing cholestatic jaundice and variceal bleeding. Liver biopsy confirmed extensive protoporphyrin deposition with cirrhosis, and so orthotopic liver transplantation was performed. Postoperatively his skin rash settled within 72 hr, and in spite of subsequent exposure to the sun he has had no further skin reaction or blistering, although he does still have some itching. He made a good recovery and was able to return to school within six months of operation. Prior to liver transplantation, the hepatic ferrochelatase activity was reduced to only 0.81 nmol zinc-protoporphyrin formed/mg protein/hr (controls 3.30 +/- 1.00 nmol zinc-protoporphyrin formed/mg protein/hr, while the red cell protoporphyrin level was markedly elevated at 188 mumol/L red cells (normal less than 1.6 mumol/L red cells). The free plasma porphyrin level of 0.95 mumol/L (normal less than 0.02 mumol/L), and the urinary and fecal porphyrin levels were also raised. Following liver grafting these elevated porphyrin levels fell rapidly, with the red cell protoporphyrin level dropping to 10% of its preoperative value, and the rest returning to virtually normal within three months of operation.}, }
@article {pmid3053555, year = {1988}, author = {Sage, R and Hann, I and Prentice, HG and Devereux, S and Corringham, R and Hoffbrand, AV and Blacklock, H and Stirling, L and Guimaraes, M and Trikka, E}, title = {A randomized trial of empirical antibiotic therapy with one of four beta-lactam antibiotics in combination with netilmicin in febrile neutropenic patients.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {22}, number = {2}, pages = {237-247}, doi = {10.1093/jac/22.2.237}, pmid = {3053555}, issn = {0305-7453}, mesh = {Agranulocytosis/*drug therapy ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Cefoperazone/therapeutic use ; Clinical Trials as Topic ; Drug Therapy, Combination/adverse effects/therapeutic use ; Feces/microbiology ; Fever/*drug therapy ; Gram-Negative Bacteria/drug effects ; Humans ; Mezlocillin/therapeutic use ; Microbial Sensitivity Tests ; Netilmicin/adverse effects/*therapeutic use ; Neutropenia/*drug therapy ; Piperacillin/therapeutic use ; Random Allocation ; Respiratory System/microbiology ; Superinfection/drug therapy ; Ticarcillin/therapeutic use ; }, abstract = {Over a two year period 174 evaluable episodes of fever in neutropenic patients were treated in a randomized study comparing four beta-lactam antibiotics, each given in combination with netilmicin. Exclusions included episodes due to viral or fungal infection, and trial violations. Most patients were receiving treatment for leukaemia, including 18% undergoing bone marrow transplantation. The overall response rate (EORTC criteria) was 66%, ranging from 56% for cefoperazone to 76% for mezlocillin. Microbial documentation was obtained in 31% of episodes; Gram-positive isolates were most frequent but Pseudomonas aeruginosa was found in 18 patients. In patients with microbiologically documented infection 70% improved, overall--from 40% with cefoperazone to 80% with piperacillin (P less than 0.05). Nephrotoxicity was seen in 6.7% and was associated with severe documented sepsis. Hypokalaemia was seen in 29% and was most marked in patients receiving ticarcillin. Rashes occurred in 6.6% overall, with no difference between the groups. Ototoxicity, shown by serial audiograms, was seen in 4.7% of patients. No evidence of vestibular dysfunction was seen in 62 patients studied. Of thirteen deaths due to the primary infection, seven were caused by Ps. aeruginosa and five by fungi.}, }
@article {pmid3043358, year = {1988}, author = {Couturier, C and Storme, B and Demeocq, F and Sirot, J and Malpuech, G and Allouche, G}, title = {[Use of ceftazidime combined with netilmicin in the treatment of febrile episodes occurring after bone marrow transplantation in children].}, journal = {Pathologie-biologie}, volume = {36}, number = {5}, pages = {562-566}, pmid = {3043358}, issn = {0369-8114}, mesh = {Bacteria/drug effects ; Bacterial Infections/*drug therapy ; *Bone Marrow Transplantation ; Ceftazidime/*administration &amp; dosage/pharmacology ; Child ; Child, Preschool ; Drug Evaluation ; Drug Therapy, Combination ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Netilmicin/*administration &amp; dosage/pharmacology ; Postoperative Complications/*drug therapy ; Sepsis/*drug therapy ; Time Factors ; Vancomycin/administration &amp; dosage/pharmacology ; }, abstract = {Thirteen episodes of fever in bone marrow transplantation recipients (23 months to 11 years old children) were treated by ceftazidime (100-200 mg/kg/j) and netilmicin (7 mg/kg/j). Vancomycin was added at the 24th hour in 10 cases of persistent fever. 6 presumed agents of infection were isolated before antibiotic treatment: blood cultures (streptococci 2, staphylococcus 1, proteus 1), fecal sample (E. coli 1), urine (E. coli 1). Modifications of aerobic fecal flora were studied under this treatment. E. coli, staphylococci and enterococci were the mainly strains isolated. There were no third generation cephalosporins resistant Gram-negative bacteria. High level resistance to aminoglycosides was observed in enterococcal strains, isolated during and after treatment. Ceftazidime-netilmicin (+/- vancomycin) was an effective and safe combination for the management of febrile neutropenic episodes.}, }
@article {pmid3287281, year = {1988}, author = {Nawa, Y and Abe, T and Imai, J and Maruyama, H}, title = {Impaired natural defence of beige (Chediak-Higashi syndrome) mice against tissue-migrating larvae of Strongyloides ratti and its reconstitution by bone marrow cells.}, journal = {Parasite immunology}, volume = {10}, number = {2}, pages = {117-126}, doi = {10.1111/j.1365-3024.1988.tb00208.x}, pmid = {3287281}, issn = {0141-9838}, mesh = {Animals ; Bone Marrow/*immunology ; Bone Marrow Transplantation ; Chediak-Higashi Syndrome/complications/*immunology ; Disease Susceptibility ; Feces/parasitology ; Immunity, Innate ; Kinetics ; Larva/growth &amp; development ; Male ; Mice ; Mice, Inbred C57BL ; Strongyloides/growth &amp; development ; Strongyloidiasis/etiology/*immunology ; }, abstract = {The susceptibility of C57BL/6-bgJ/bgJ mice, which exhibit a murine counterpart of the Chediak-Higashi syndrome, to infection with Strongyloides ratti was examined. After a primary infection, the peak of the daily larval output in faeces (LPG) of bgJ/bgJ mice was approximately twice as high as that of their littermate bgJ/+mice. The total number of tissue migrating larvae recovered from bgJ/bgJ mice at 36 h after infection was also approximately twice as high as that from bgJ/+mice. However, after a primary infection, bgJ/bgJ mice could completely expel adult worms in the intestine by day 14. When an equal number of tissue migrating larvae obtained from the head of +/+ mice were implanted into bgJ/bgJ and bgJ/+mice, the magnitude and the kinetics of LPG were comparable between them, indicating that in both groups implanted larvae established in the intestine to become adult worms and then they were expelled by day 13. Thus, immune mechanisms involved in worm expulsion of bgJ/bgJ mice were comparable to those of bgJ/+mice. The higher susceptibility of bgJ/bgJ mice could be reduced to the level of bgJ/+mice by bone marrow grafting from bgJ/+mice 6 weeks prior to infection. Furthermore, when lethally irradiated bgJ/bgJ mice or bgJ/+mice were reconstituted with either type of bone marrow cells, the mice given bgJ/bgJ bone marrow cells showed higher susceptibility to infection with S. ratti regardless of the genotype of the recipients. These results indicate that the impaired natural defence of bgJ/bgJ mice is predetermined at the level of haemopoietic stem cells.}, }
@article {pmid3278130, year = {1988}, author = {Flanigan, RC and Reckard, CR and Lucas, BA}, title = {Colonic complications of renal transplantation.}, journal = {The Journal of urology}, volume = {139}, number = {3}, pages = {503-506}, doi = {10.1016/s0022-5347(17)42504-3}, pmid = {3278130}, issn = {0022-5347}, mesh = {Adult ; Colitis/etiology ; Colonic Diseases/*etiology ; Enterocolitis, Pseudomembranous/etiology ; Female ; Humans ; Ischemia/etiology ; *Kidney Transplantation ; Male ; Middle Aged ; Necrosis ; *Postoperative Complications ; }, abstract = {Colonic complications of renal transplantation occur in 1.9 per cent of the cases. In our series of 587 consecutive renal transplants recipients 3 (0.51 per cent) had colonic complications, including 2 with ischemic colitis and 1 with pseudomembranous colitis. A review of 8 large series describing 2,539 additional renal transplant patients revealed 55 with significant colonic complications. The most common complication was ischemic colitis, which occurred in 29 patients, followed by diverticulitis in 17, pseudomembranous colitis in 5, appendicitis in 3, hemorrhagic proctitis in 1, a disrupted appendiceal stump in 1 and fecal impaction in 1. Etiological factors that may be important in the development of these colonic complications are uremia, blood volume redistribution, immunosuppressive therapy, antibiotic therapy, irradiation and previous retroperitoneal surgery.}, }
@article {pmid3338345, year = {1988}, author = {Baeten, C and Spaans, F and Fluks, A}, title = {An implanted neuromuscular stimulator for fecal continence following previously implanted gracilis muscle. Report of a case.}, journal = {Diseases of the colon and rectum}, volume = {31}, number = {2}, pages = {134-137}, doi = {10.1007/BF02562646}, pmid = {3338345}, issn = {0012-3706}, mesh = {Adult ; Electric Stimulation ; *Electrodes, Implanted ; Fecal Incontinence/complications/*surgery ; Female ; Humans ; Manometry ; Muscle Contraction ; Muscles/physiology/*transplantation ; Rectovaginal Fistula/complications ; }, abstract = {A young woman had been treated previously with a gracilis muscle transposition because of anal atresia thus enabling her to maintain continence by active muscle contraction, which, however, she could sustain for only a few minutes. Implantation of a neuromuscular stimulator resulted in perfectly controllable sphincter function.}, }
@article {pmid3375583, year = {1988}, author = {McKellar, QA and Eckersall, PD and Duncan, JL and Armour, J}, title = {Forms of bovine pepsinogen in plasma from cattle with three different 'syndromes' of Ostertagia ostertagi infection.}, journal = {Research in veterinary science}, volume = {44}, number = {1}, pages = {29-32}, pmid = {3375583}, issn = {0034-5288}, mesh = {Animals ; Cattle ; Cattle Diseases/blood/*parasitology ; Feces/parasitology ; Ostertagiasis/blood/*veterinary ; Parasite Egg Count/veterinary ; Pepsinogens/*blood ; Trichostrongyloidiasis/*veterinary ; }, abstract = {Calves infected orally with third stage larvae of Ostertagia ostertagi or infected with adult O ostertagi by direct transplantation into the abomasum had raised plasma pepsinogen activity, as did four-year-old dairy cattle challenged with O ostertagi third stage larvae on five occasions. Using fast protein liquid chromatography two forms of pepsinogen; pepsinogen 1 (PG1) and pepsinogen 2 (PG2) were identified in each of the parasitic infection regimes.}, }
@article {pmid3292884, year = {1988}, author = {Veenendaal, D and de Boer, F and Van der Waaij, D}, title = {Effect of selective decontamination of the digestive tract of donor and recipient on the occurrence of murine delayed-type graft-versus-host disease.}, journal = {Medical microbiology and immunology}, volume = {177}, number = {3}, pages = {133-144}, pmid = {3292884}, issn = {0300-8584}, mesh = {Animals ; Aztreonam/pharmacology ; *Bone Marrow Transplantation ; Enterobacteriaceae/drug effects/growth &amp; development ; Feces/microbiology ; Female ; *Graft vs Host Disease ; H-2 Antigens/immunology ; *Hypersensitivity, Delayed ; Intestines/*microbiology ; Male ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Transplantation, Homologous ; }, abstract = {In the present study we investigated the occurrence of delayed-type graft-versus-host disease (DT-GvHD) after allogeneic bone marrow transplantation (BMT) between two H-2 incompatible mouse strains. BMT was performed on mice with a conventional intestinal microflora as well as on mice in which the Enterobacteriaceae were selectively eliminated from the intestinal microflora by oral antibiotic treatment. None of the conventional or the selectively decontaminated (SD) chimaeric mice suffering from DT-GvHD died of bacteraemia. While DT-GvHD was mitigated when C3H/He recipient mice were SD-treated, this was not the case when C57B1/6J recipient mice were SD-treated. SD-treatment of the digestive tract of donor mice only mitigated DT-GvHD when the recipients were also SD-treated. We conclude that Enterobacteriaceae in the digestive tract may only play a minor role, if any, in the occurrence of DT-GvHD. Instead, we postulate that in this study DT-GvHD was determined by differences in the composition of the resident intestinal microflora (IM) of both mouse strains together with the cellular composition of the bone marrow graft. The interaction between antigenic components of the recipient's IM and the developing donor immune system in the recipient as a possible cause for DT-GvHD is discussed.}, }
@article {pmid3067772, year = {1988}, author = {Smith, ED and Stephens, FD and Holschneider, AM and Nixon, HH and Peña, A}, title = {Operations to improve continence after previous surgery.}, journal = {Birth defects original article series}, volume = {24}, number = {4}, pages = {447-479}, pmid = {3067772}, issn = {0547-6844}, mesh = {Child ; Child, Preschool ; Fecal Incontinence/*surgery ; Humans ; Muscle, Smooth/transplantation ; Muscles/surgery/transplantation ; *Postoperative Complications ; Surgical Flaps ; }, }
@article {pmid3696779, year = {1987}, author = {Behnke, JM and Williams, DJ and Hannah, J and Pritchard, DI}, title = {Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): the capacity of adult worms to survive following transplantation to recipient mice.}, journal = {Parasitology}, volume = {95 (Pt 3)}, number = {}, pages = {569-581}, doi = {10.1017/s0031182000057991}, pmid = {3696779}, issn = {0031-1820}, mesh = {Animals ; Antibodies, Helminth/immunology ; Antibody Specificity ; Feces/parasitology ; Female ; Gerbillinae ; Heligmosomatoidea/immunology/isolation &amp; purification/*physiology ; Host-Parasite Interactions ; Immunoglobulin G/analysis ; Male ; Mice ; Nematode Infections/*immunology/parasitology ; Parasite Egg Count ; Time Factors ; }, abstract = {Chronic primary infections with Heligmosomoides polygyrus (Nematospiroides dubius) are still relatively poorly documented, particularly in relation to the role of host resistance in limiting worm survival. In the present work the duration of infection with H. polygyrus was studied in CFLP mice given doses of infective larvae ranging from 50 to 500 L3. The least heavily infected (50 L3) group ceased egg production earliest (week 36) whereas eggs were still detected in the faeces of mice given 500 larvae in week 42. At autopsy (week 42) mice given 50 larvae had virtually lost their entire worm burden with 5 out of 11 mice still harbouring a single worm each. However, all the mice in the group given 500 larvae were still infected, the highest worm burden being 93. The concentration of serum IgG1 and specific antibody was highest in mice given 500 larvae, but sera taken from mice with declining worm burdens 19-38 weeks post-infection did not contain detectable host-protective antibody. During the course of infection in CFLP mice, H. polygyrus sustained irreversible changes in its capacity for subsequent survival. Thus, adult worms transferred to naive mice 2, 7, 14, 30 or 36 weeks post-infection did not live longer than worms of a comparable age in the respective donor group. In contrast, primary infection worms taken from jirds in which expulsion is usually completed by 6 weeks post-infection, re-established in mice and survived considerably longer than in the group of donor jirds. These results were discussed in relation to the possible interactions between parasite senility and immunomodulation, and host resistance in limiting primary infections with H. polygyrus in mice and jirds.}, }
@article {pmid3424438, year = {1987}, author = {Larson, G and Falk, P and Andersson, L and Hoskins, LC}, title = {Shedding of epithelial blood group active glycosphingolipids and their degradation by bacterial glycosidases.}, journal = {Transplantation proceedings}, volume = {19}, number = {6}, pages = {4433-4434}, pmid = {3424438}, issn = {0041-1345}, mesh = {ABO Blood-Group System/*immunology ; Bacteria/enzymology ; Epithelium/immunology ; Feces/immunology ; Glycoside Hydrolases/*metabolism ; Glycosphingolipids/immunology/*metabolism ; Humans ; Intestines/*immunology ; Lewis Blood Group Antigens/*immunology ; Meconium/*immunology ; }, }
@article {pmid3326742, year = {1987}, author = {Pfaller, M and Cabezudo, I and Koontz, F and Bale, M and Gingrich, R}, title = {Predictive value of surveillance cultures for systemic infection due to Candida species.}, journal = {European journal of clinical microbiology}, volume = {6}, number = {6}, pages = {628-633}, pmid = {3326742}, issn = {0722-2211}, mesh = {Bone Marrow Transplantation ; Candida/*isolation &amp; purification ; Candidiasis/complications/*diagnosis ; Feces/*microbiology ; Humans ; Leukemia/complications ; Oropharynx/*microbiology ; Predictive Value of Tests ; Urine/*microbiology ; }, abstract = {Weekly fungal surveillance cultures (1,542 cultures) of urine (475), stool (520) and oropharyngeal (547) specimens from 111 patients on the bone marrow transplant and hematologic malignancy services were analyzed. Forty-three percent of the patients were colonized by Candida albicans and 10.8% by Candida tropicalis. There were 22 proven systemic fungal infections, ten due to Candida albicans, eight to Candida tropicalis, one each to Candida pseudotropicalis and Torulopsis glabrata, and two to Aspergillus species. Positive surveillance cultures for Candida tropicalis were highly predictive of systemic infection. The finding of two or more positive cultures yielded high positive predictive values (100%) as a function of body site. Positive surveillance cultures for Candida albicans were not predictive of disease but negative cultures for Candida albicans and Candida tropicalis had a high negative predictive value (95-99%). Surveillance culture data for specific Candida species may aid in diagnostic and therapeutic decision making.}, }
@article {pmid3312287, year = {1987}, author = {Hamilton, DJ and Ulness, BK and Baugher, LK and Counts, GW}, title = {Comparison of a novel trimethoprim-sulfamethoxazole-containing medium (XT80) with kanamycin agar for isolation of antibiotic-resistant organisms from stool and rectal cultures of marrow transplant patients.}, journal = {Journal of clinical microbiology}, volume = {25}, number = {10}, pages = {1886-1890}, pmid = {3312287}, issn = {0095-1137}, support = {CA18029/CA/NCI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/drug effects/growth &amp; development/*isolation &amp; purification ; *Bone Marrow Transplantation ; Corynebacterium/drug effects/growth &amp; development/isolation &amp; purification ; Culture Media ; Drug Combinations/pharmacology ; Drug Resistance, Microbial ; Enterobacteriaceae/drug effects/growth &amp; development/isolation &amp; purification ; Feces/microbiology ; Humans ; Kanamycin/*pharmacology ; Rectum/microbiology ; Sepsis/microbiology ; Staphylococcus epidermidis/drug effects/growth &amp; development/isolation &amp; purification ; Sulfamethoxazole/*pharmacology ; Trimethoprim/*pharmacology ; Trimethoprim, Sulfamethoxazole Drug Combination ; }, abstract = {A new medium (XT80) containing trimethoprim-sulfamethoxazole (TMP-SMZ) was characterized and compared with kanamycin-containing tryptic soy agar (KA) for the recovery of multiply resistant organisms (MRO) in rectal and stool cultures. Cultures from 151 patients hospitalized for bone marrow transplantation were screened for MRO. A total of 366 MRO were recovered from 702 cultures on 94 patients during a 6-month period. XT80 detected more gram-negative bacilli and Corynebacterium spp. than KA. Detection of Staphylococcus spp. was equivalent for the two media. Multiple-antibiotic resistance, defined as resistance to three or more classes of antibiotics, was confirmed by standard agar disk diffusion susceptibility testing. Growth on XT80 correctly identified heteroresistant strains of methicillin-resistant Staphylococcus spp. XT80 more rapidly detected thymidine-dependent mutants of Staphylococcus spp. and members of the family Enterobacteriaceae. Lipophilic Corynebacterium spp., including Corynebacterium group JK, also were more readily detected with XT80. TMP-SMZ given as prophylaxis against Pneumocystis carinii infection exerts a selective pressure on organisms that colonize immunocompromised patients and appears to select for colonization with MRO. Colonization with MRO preceded infection for 94% of 36 patients who developed bacteremia. XT80 is a useful screening tool; growth on this medium correlates closely with resistance to TMP-SMZ and is as accurate a predictor as KA for the carriage of MRO.}, }
@article {pmid3441986, year = {1987}, author = {Kaplan, VM and Sitkovskii, NB and Dan'shin, TI}, title = {[Smooth muscle plasty in pediatric proctology].}, journal = {Vestnik khirurgii imeni I. I. Grekova}, volume = {139}, number = {9}, pages = {84-87}, pmid = {3441986}, issn = {0042-4625}, mesh = {Adolescent ; Anal Canal/surgery ; Child ; Fecal Incontinence/etiology/*surgery ; Humans ; Muscle, Smooth/*transplantation ; Rectal Prolapse/etiology/*surgery ; Rectum/abnormalities/*surgery ; *Surgical Flaps ; }, }
@article {pmid3658407, year = {1987}, author = {Hévizi, M}, title = {[Continent colostomy created by transplantation of a pedicled colon muscle].}, journal = {Orvosi hetilap}, volume = {128}, number = {36}, pages = {1889-1891}, pmid = {3658407}, issn = {0030-6002}, mesh = {Colostomy/*methods ; Fecal Incontinence/prevention &amp; control ; Female ; Humans ; Middle Aged ; Muscle, Smooth/transplantation ; Rectal Neoplasms/*surgery ; Surgical Flaps ; }, }
@article {pmid3656017, year = {1987}, author = {Schärli, AF}, title = {Anorectal incontinence: diagnosis and treatment.}, journal = {Journal of pediatric surgery}, volume = {22}, number = {8}, pages = {693-701}, doi = {10.1016/s0022-3468(87)80607-3}, pmid = {3656017}, issn = {0022-3468}, mesh = {Anal Canal/physiopathology/surgery ; Child ; Fecal Incontinence/diagnosis/physiopathology/*therapy ; Humans ; Manometry ; Muscles/transplantation ; Rectum/physiopathology/surgery ; }, abstract = {In correcting anorectal incontinence, the analysis of all known factors responsible for a lack of function is mandatory. Besides anamnestic and clinical data, manometric investigation is especially helpful. Continence may be improved by conservative measures (biofeedback training, muscle training, and drugs). The indication for surgical procedures depends on clinical and manometric findings: missed portions of the sphincteric muscle complex are reintegrated with a repull-through procedure. In some cases, Kottmeier's levatorplasty or a modification of it has led to some improvement of continence. Whenever a call to stool was present, gracilis transposition has markedly improved anorectal function in 22 of 27 operated patients. Free transplantation of palmaris longus muscle has not proven to be of functional advantage. Doubling the circular colonic musculature and an S-shaped anoplasty at the time of the primary pull-through procedure may lead to continence in the future.}, }
@article {pmid3308740, year = {1987}, author = {Wells, CL and Ferrieri, P and Weisdorf, DJ and Rhame, FS}, title = {The importance of surveillance stool cultures during periods of severe neutropenia.}, journal = {Infection control : IC}, volume = {8}, number = {8}, pages = {317-319}, doi = {10.1017/s0195941700066406}, pmid = {3308740}, issn = {0195-9417}, support = {AI 23484/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Agranulocytosis/*complications ; Anti-Bacterial Agents/pharmacology/therapeutic use ; *Bone Marrow Transplantation ; Child ; Drug Combinations/pharmacology/therapeutic use ; Drug Resistance, Microbial ; Feces/*microbiology ; Gram-Negative Bacteria/drug effects/*isolation &amp; purification ; Humans ; Immune Tolerance ; Neutropenia/*complications ; Prospective Studies ; Sepsis/drug therapy/*etiology/microbiology ; Sulfamethoxazole/pharmacology/therapeutic use ; Ticarcillin/pharmacology/therapeutic use ; Tobramycin/pharmacology/therapeutic use ; Trimethoprim/pharmacology/therapeutic use ; Trimethoprim, Sulfamethoxazole Drug Combination ; }, abstract = {The correlation of fecal gram-negative bacilli (GNB), neutropenia, and bacteremia was studied in 45 bone marrow transplant recipients. Weekly stool cultures were prospectively monitored for GNB resistant to routine prophylactic and empiric antimicrobial agents. Seven cases of GNB bacteremia occurred in 45 patients described as follows. Twenty-three patients had no fecal or blood GNB. Fifteen patients had fecal GNB and no blood GNB; three of these latter patients had less than or equal to 50/mm3 circulating white blood cells (WBC) at the time of isolation of fecal GNB but two of the three were concurrently receiving appropriate empiric antibiotics. Two patients had blood GNB but no fecal GNB: one patient had a trimethoprim/sulfamethoxazole (TMP-SMZ)-sensitive isolate that would not be detectable in the feces by our methodology and one patient had feces analyzed only after the bacteremic event. Five patients had fecal GNB and blood GNB: one of these patients did not have a fecal sample analyzed prior to bacteremia but the remaining four patients had the same species/antibiogram of GNB isolated from the feces two to three days prior to the detection of bacteremia. Thus, the fecal GNB could have been used to predict the antibiogram of the subsequent blood GNB. In addition, all four of these latter bacteremic patients had less than or equal to 50/mm3 circulating WBC at the time of documented fecal GNB. Thus, bone marrow transplant recipients with fecal GNB coupled with severe neutropenia (less than or equal to 50/mm3 circulating WBC) were more likely to develop bacteremia (P less than 0.02) than were those with fecal GNB and greater than 50/mm3 circulating WBC.}, }
@article {pmid3622056, year = {1987}, author = {Gögler, H and Kaminski, M}, title = {[Therapy of anal incontinence with a Schmidt free-muscle transplant].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {58}, number = {7}, pages = {492-495}, pmid = {3622056}, issn = {0009-4722}, mesh = {Adult ; Fecal Incontinence/diagnosis/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Middle Aged ; Postoperative Complications/diagnosis ; *Surgical Flaps ; }, abstract = {Between 1980 to 1985 in ten patients with complete anal incontinence the autologous muscle graft introduced by Schmidt has been used. The operative results obtained were good for satisfactory in nine patients whereas in one patient the operation failed.}, }
@article {pmid3496494, year = {1987}, author = {Schraut, WH and Lee, KK and Sitrin, M}, title = {Recipient growth and nutritional status following transplantation of segmental small-bowel allografts.}, journal = {The Journal of surgical research}, volume = {43}, number = {1}, pages = {1-9}, doi = {10.1016/0022-4804(87)90039-4}, pmid = {3496494}, issn = {0022-4804}, mesh = {Age Factors ; Animals ; Cyclosporins/therapeutic use ; Graft Survival/drug effects ; *Growth ; Ileum/transplantation ; Intestine, Small/physiology/*transplantation ; Jejunum/transplantation ; *Nutritional Status ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; Serum Albumin/metabolism ; Triglycerides/blood ; Vitamins/blood ; }, abstract = {Concerning small-bowel transplantation in children, the question arises whether a segmental small-bowel graft from an adult donor would permit normal growth of the young recipient. Orthotopic small-bowel transplantation was performed in 4- to 6-week-old Lewis rats weighing 100-135 g. The entire small bowel of the recipient was replaced with an intestinal allograft consisting of the entire small bowel (N = 6), the jejunum (N = 6), or the ileum (N = 6) from adult Brown Norway rats. Immunosuppression with cyclosporine (15 mg/kg im) on alternate days for 4 weeks achieved graft acceptance of indefinite duration. Six and twelve months after transplantation, all recipients demonstrated normal global nutritional parameters (hematocrit, serum albumin) and gained weight at a rate comparable to that for age-matched controls. Nutritional deficiencies did not become apparent clinically. By 10 to 12 months, the levels of fat-soluble vitamins (A and E) were reduced significantly in recipients of segmental grafts. Vitamin B12 levels were also reduced but not significantly. Fecal fat was significantly elevated in all rats with grafts (3.2 +/- 1.0 to 4.8 +/- 0.9 g fat/100 g stool; controls, 1.8 +/- 0.4), but the increase was most pronounced in those with jejunal grafts (4.7 +/- 0.9). This was paralleled by a reduction in serum triglyceride levels in all transplanted rats, a reduction which reverted to normal by 10 to 12 months for rats with entire small-bowel grafts but not for those with segmental grafts. Graft biopsy demonstrated normal intestinal architecture with villus hyperplasia of segmental grafts.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid3312020, year = {1987}, author = {Vlaspolder, F and de Zeeuw, G and Rozenberg-Arska, M and Egyedi, P and Verhoef, J}, title = {The influence of flucloxacillin and amoxicillin with clavulanic acid on the aerobic flora of the alimentary tract.}, journal = {Infection}, volume = {15}, number = {4}, pages = {241-244}, pmid = {3312020}, issn = {0300-8126}, mesh = {Adolescent ; Adult ; Amoxicillin/pharmacology/*therapeutic use ; Amoxicillin-Potassium Clavulanate Combination ; Bacteria, Aerobic/*drug effects/growth &amp; development ; Bone Transplantation ; Child ; Clavulanic Acids/pharmacology/*therapeutic use ; Cloxacillin/*analogs &amp; derivatives ; Digestive System/*microbiology ; Drug Combinations/pharmacology/therapeutic use ; Enterobacteriaceae/drug effects/growth &amp; development ; Feces/microbiology ; Female ; Floxacillin/pharmacology/*therapeutic use ; Humans ; Male ; Middle Aged ; Nasopharynx/microbiology ; Orthognathic Surgical Procedures ; Premedication ; Random Allocation ; Yeasts/growth &amp; development ; }, abstract = {In a randomized study, 42 patients undergoing extensive maxillo-facial surgery (correction of the position of the mandible or maxilla by using autologous bone transplants) received prophylactically ten-day courses of either flucloxacillin or amoxicillin with clavulanic acid. Patients were comparable with regard to age and type of surgery. During the prophylactic treatment the effect of antibiotics used on the microbial flora of the alimentary tract was studied. Patients receiving flucloxacillin showed increased numbers of Klebsiella spp. isolated from the faeces (59% of the patients versus 19% of the patients receiving amoxicillin with clavulanic acid). Patients receiving amoxicillin with clavulanic acid showed higher colonization rates of oropharynx with Enterobacteriaceae than patients receiving flucloxacillin (ten patients versus five patients). 60% of those strains isolated from patients receiving amoxicillin with clavulanic acid were resistant to this combination, as compared to 20% of gram-negative bacilli isolated from patients receiving flucloxacillin. In 50% of patients receiving amoxicillin with clavulanic acid, colonization of the gut with yeast occurred, as compared to 18% of patients receiving flucloxacillin. Only one infection leading to a partial loss of the graft was seen in the group of patients receiving flucloxacillin.}, }
@article {pmid3603230, year = {1987}, author = {Skácel, V and Laichman, S}, title = {[An anal neosphincter from the internal obturator muscle].}, journal = {Rozhledy v chirurgii : mesicnik Ceskoslovenske chirurgicke spolecnosti}, volume = {66}, number = {6}, pages = {394-399}, pmid = {3603230}, issn = {0035-9351}, mesh = {Adolescent ; Adult ; Anal Canal/*surgery ; Child ; Fecal Incontinence/*surgery ; Humans ; Male ; Methods ; Middle Aged ; Muscles/*transplantation ; }, }
@article {pmid3151580, year = {1987}, author = {Ji, ZL and Guo, ET}, title = {[Gracilis muscle transplantation for the treatment of incontinence of the sphincter ani].}, journal = {Zhonghua zheng xing shao shang wai ke za zhi = Zhonghua zheng xing shao shang waikf [i.e. waike] zazhi = Chinese journal of plastic surgery and burns}, volume = {3}, number = {2}, pages = {116-7, 157}, pmid = {3151580}, issn = {1000-7806}, mesh = {Adolescent ; Anal Canal/*surgery ; Child ; Fecal Incontinence/*surgery ; Humans ; Male ; Middle Aged ; Muscles/*transplantation ; }, }
@article {pmid3593674, year = {1987}, author = {Ivan, M}, title = {Absorption and secretion of 65Zn in the stomach and intestinal tract of sheep exchanging digesta via duodenal re-entrant cannulas.}, journal = {The British journal of nutrition}, volume = {57}, number = {3}, pages = {479-488}, doi = {10.1079/bjn19870055}, pmid = {3593674}, issn = {0007-1145}, mesh = {Animals ; Digestive System/*metabolism ; Feces/analysis ; Gastrointestinal Contents/*metabolism/transplantation ; *Intestinal Absorption ; Male ; Sheep/*metabolism ; Zinc/*metabolism ; }, abstract = {The absorption and secretion of 65Zn in the stomach and intestinal tract regions was studied in sets of two and three sheep which were exchanging digesta via re-entrant cannulas in the proximal duodenum. One sheep from each of the three three-sheep sets was dosed intraruminally with the radioisotope. One sheep from the three two-sheep sets received an intravenous dose. Measurements of 65Zn in blood plasma from intraruminally dosed sheep showed that there was no apparent absorption from the stomach region. Measurements from sheep receiving radioactive digesta intraduodenally showed that mean apparent absorption of 65Zn was 0.07 and mean true absorption was 0.103. There was a large variation in endogenous recycling of 65Zn into the stomach region. Secretion of 65Zn into the stomach and intestinal regions in the intravenously dosed sheep of the two-sheep sets was calculated on the basis of total recovery over 10 d in the digesta and faeces. The present study showed that for every 1 molecule Zn secreted into the stomach region, 2.1 molecules were secreted into the intestinal tract region.}, }
@article {pmid3319373, year = {1987}, author = {Sherlock, CH and Burdge, DR and Smith, JA}, title = {Does Aeromonas hydrophila preferentially colonize the bowels of patients with hematologic malignancies?.}, journal = {Diagnostic microbiology and infectious disease}, volume = {7}, number = {1}, pages = {63-68}, doi = {10.1016/0732-8893(87)90072-1}, pmid = {3319373}, issn = {0732-8893}, mesh = {Adult ; Aeromonas/*isolation &amp; purification ; Anti-Bacterial Agents/therapeutic use ; Bacterial Infections/*complications/drug therapy ; Bone Marrow Transplantation ; Feces/microbiology ; Female ; Humans ; Leukemia, Myeloid, Acute/*complications ; Lymphoproliferative Disorders/*complications ; Male ; Middle Aged ; Neutropenia/etiology ; }, abstract = {Weekly cultures of stools from neutropenic patients and bone marrow transplant recipients yielded Aeromonas hydrophila from 8% of 88 patients over a 2-yr period. During this time stools in the routine enteric laboratory yielded A. hydrophila in 0.24% of 1632 patients. Although the patient groups and culture methods were not directly comparable, this significant difference in isolation rate (p less than 0.001) may reflect a higher colonization rate in the immunocompromised patient.}, }
@article {pmid2436760, year = {1987}, author = {Fanucchi, MP and Kinahan, JJ and Samuels, LL and Hancock, C and Chou, TC and Niedzwiecki, D and Farag, F and Vidal, PM and DeGraw, JI and Sternberg, SS}, title = {Toxicity, elimination, and metabolism of 10-ethyl-10-deazaaminopterin in rats and dogs.}, journal = {Cancer research}, volume = {47}, number = {9}, pages = {2334-2339}, pmid = {2436760}, issn = {0008-5472}, support = {CA-05826/CA/NCI NIH HHS/United States ; CA-18856/CA/NCI NIH HHS/United States ; CA-22764/CA/NCI NIH HHS/United States ; }, mesh = {Aminopterin/*analogs &amp; derivatives/metabolism/toxicity ; Animals ; Dogs ; Mathematics ; Polyglutamic Acid/metabolism ; Rats ; Tissue Distribution ; }, abstract = {10-Ethyl-10-deazaaminopterin (10-EdAM) is an antifolate compound with greater therapeutic activity than methotrexate against transplanted tumors in mice. When given weekly for 3 weeks, the 10% lethal dose in rats was 125 mg/kg (i.p.) and in dogs it was 2.5 mg/kg (i.v.). The major histopathological findings in intoxicated animals were damage to the mucosa of the gastrointestinal tract in rats and dogs and hypocellularity of the marrow in rats. The elimination of 50 mg/kg of 10-EdAM from the plasma of rats was triexponential with a terminal phase t1/2 of 18.5 h but a mean residence time of 0.7 h. The primary route of elimination in rats was biliary secretion of parent compound and eventual excretion of the parent compound and the deglutamate metabolite in the feces; the 7-hydroxy metabolite was also present in plasma, bile, and feces. Biliary elimination was independent of dose over a 5-fold range. The elimination of 10-EdAM from the plasma of dogs was also triexponential with a mean terminal phase t1/2 of 9.1 h and a mean residence time of 2.5 h; nonrenal clearance was the primary route of elimination. The pharmacokinetic parameters were independent of dose over the range of 0.25 to 5.0 mg/kg. High tissue concentrations of 10-EdAM were observed initially in liver, kidney, and small intestine of rats, while concentrations in bone marrow were low. Some polyglutamate formation was observed in these tissues as early as 0.5 h after drug administration but declined over 72 h.}, }
@article {pmid3297772, year = {1987}, author = {Guiot, HF and Biemond, J and Klasen, E and Gratama, JW and Kramps, JA and Zwaan, FE}, title = {Protein loss during acute graft-versus-host disease: diagnostic and clinical significance.}, journal = {European journal of haematology}, volume = {38}, number = {2}, pages = {187-196}, doi = {10.1111/j.1600-0609.1987.tb01160.x}, pmid = {3297772}, issn = {0902-4441}, mesh = {Acute Disease ; Adolescent ; Adult ; Bone Marrow Transplantation ; Capillary Permeability ; Graft vs Host Disease/*physiopathology ; Humans ; Lung/blood supply ; Middle Aged ; Prognosis ; Protease Inhibitors/blood ; Proteinase Inhibitory Proteins, Secretory ; *Proteins ; Serum Albumin/*metabolism ; }, abstract = {In 31 consecutive patients who received an allogeneic bone marrow transplantation the loss of proteins during the period at risk for acute graft-versus-host disease (aGVHD) was studied in order to determine whether the quantity of protein loss could be used for grading the severity of aGVHD. It was shown that the grade classified on the basis of the severity of skin rash, the quantity of diarrhea and the seriousness of cholestasis, correlated with serum albumin loss, intestinal plasma loss (expressed by the intestinal alpha 1-antitrypsin clearance) and the occurrence of inflammatory cells (leukocytes) in feces. The quantity of albumin lost by intestinal route accounted for only one third of the total albumin loss. To investigate whether the remaining part of it could be explained by capillary leakage elsewhere in the body, leakage of antileukoprotease from the tissue of the respiratory tract into the blood was measured. It was shown that the serum concentration of this proteinase inhibitor correlated with albumin loss. This means that capillary leakage also occurs in the lung during aGVHD. In conclusion, the loss of proteins can be used as a parameter of the severity of aGVHD once the proper diagnosis has been established. It appears that a combination of the current 'familiar' grading system and SAL yields a more objective classification system with a greater prognostic value.}, }
@article {pmid2879147, year = {1987}, author = {Cohen, J and Moore, RH and Al Hashimi, S and Jones, L and Apperley, JF and Aber, VR}, title = {Antibody titres to a rough-mutant strain of Escherichia coli in patients undergoing allogeneic bone-marrow transplantation. Evidence of a protective effect against graft-versus-host disease.}, journal = {Lancet (London, England)}, volume = {1}, number = {8523}, pages = {8-11}, doi = {10.1016/s0140-6736(87)90700-8}, pmid = {2879147}, issn = {0140-6736}, mesh = {Acute Disease ; Adolescent ; Adult ; Aged ; Antibodies, Bacterial/*analysis ; *Bone Marrow Transplantation ; Child ; Cholestasis/immunology ; Escherichia coli/*immunology ; Female ; Graft vs Host Disease/immunology/*prevention &amp; control ; Humans ; Immunoglobulin M/analysis ; Leukemia, Myeloid/therapy ; Male ; Middle Aged ; Sex Factors ; Transplantation, Homologous ; }, abstract = {Much clinical and experimental evidence suggests that infection and graft-versus-host disease (GvHD) are commonly associated as complications of bone-marrow transplantation (BMT). A likely basis for this association is the gram-negative faecal flora,the origin of many septicaemias and a source of bacterial endotoxin, which has potent immunostimulatory effects. A rough-mutant strain, Escherichia coli J5, has only core determinants in its endotoxin,and antibodies to E coli J5 protect animals and human beings from the consequences of septic shock. Naturally occurring antibodies to E coli J5 ("anti-endotoxin") were assayed in serum from patients undergoing BMT, healthy controls, and patients with obstructive jaundice. BMT recipients had significantly lower titres than the other two groups. Furthermore, the titre of IgM class anti-J5 antibody was significantly associated with protection from GvHD.}, }
@article {pmid3562059, year = {1987}, author = {Abe, T and Nawa, Y}, title = {Reconstitution of mucosal mast cells in W/WV mice by adoptive transfer of bone marrow-derived cultured mast cells and its effects on the protective capacity to Strongyloides ratti-infection.}, journal = {Parasite immunology}, volume = {9}, number = {1}, pages = {31-38}, doi = {10.1111/j.1365-3024.1987.tb00486.x}, pmid = {3562059}, issn = {0141-9838}, mesh = {Animals ; Immunization, Passive ; Intestinal Mucosa/*immunology ; Kinetics ; Male ; Mast Cells/*immunology/transplantation ; Mice ; Mice, Inbred C57BL ; Strongyloides/immunology ; Strongyloidiasis/*immunology ; }, abstract = {Bone marrow-derived cultured mast cells (BMMC) were transferred intravenously into W/WV mice to examine if they could reconstitute defective mucosal mast cell response or defective protective capacity against infection with Strongyloides ratti. When mast cell growth factor-producing activity of W/WV mice were examined, mesenteric lymph node cells obtained at 7 to 14 days after infection could produce this factor in vitro by stimulation with S. ratti-adult worm antigen. A single injection of BMMC (1 X 10(7] on day 7 post-infection (p.i.) neither caused an increase in number of intestinal mucosal mast cells not altered the kinetics of faecal larval output (LPG). On the other hand, serial injections of BMMC (5 X 10(6] from day 5 to 10 p.i. (total 3 X 10(7) cells) resulted in the significant increase in number of intestinal mucosal mast cells. However, this treatment too could not alter the kinetics of LPG. Therefore, adoptive transfer of BMMC could cause the increase in number of histologically detectable-mucosal mast cells, but these cells are, by themselves, not sufficient to cause the expulsion of S. ratti adult worms from the intestine.}, }
@article {pmid3467122, year = {1987}, author = {Reiss, B and Weiss, CJ and Tanaka, T and Reddy, B and Williams, GM}, title = {Effects of bile acids on carcinogen-exposed rat colon in organ culture and as subsequent long-term transplants.}, journal = {Journal of the National Cancer Institute}, volume = {78}, number = {1}, pages = {107-113}, doi = {10.1093/jnci/78.1.107}, pmid = {3467122}, issn = {0027-8874}, support = {CA-29602/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bile Acids and Salts/isolation &amp; purification/*pharmacology ; Colon/*drug effects/metabolism/pathology/transplantation ; DNA Replication/drug effects ; Deoxycholic Acid/pharmacology ; Dietary Fats/administration &amp; dosage ; Feces/analysis ; Female ; Intestinal Mucosa/drug effects/ultrastructure ; Male ; Methylnitronitrosoguanidine/*toxicity ; Methylnitrosourea/*toxicity ; Organ Culture Techniques ; Rats ; Rats, Inbred F344 ; }, abstract = {Rat (F344) colon fragments in organ culture were exposed for 4 to 6 hours to carcinogens and then for 4 days to deoxycholic acid or fecal extracts containing a mixture of in vivo-produced bile acids from animals fed low- or high-fat diets. Following exposures during culture, the fragments were transplanted into the mammary fat pads of syngeneic rats. The transplanted fragments survived for at least 1 year with preservation of crypt architecture and with continued DNA and mucin synthesis. Exposure in culture to N-methyl-N'-nitro-N-nitrosoguanidine (CAS: 70-25-7) or N-methyl-N-nitrosourea (CAS: 684-93-5) resulted in hypercellularity, hyperplasia, and cellular atypia in the transplants; but, in contrast to transplants from colon adenocarcinomas, no tumors formed. Exposure in culture to deoxycholic acid subsequent to N-methyl-N-nitrosourea or N-methyl-N'-nitro-N-nitrosoguanidine resulted in greater cellular abnormalities in transplants. Exposure after N-methyl-N-nitrosourea to fecal extracts from rats on a high-fat diet also enhanced the pathologic changes, whereas similar extracts from rats on a low-fat diet did not alter the pathology resulting from N-methyl-N-nitrosourea or N-methyl-N'-nitro-N-nitrosoguanidine exposures. It is concluded that bile acids, including those formed in vivo, facilitate the expression of carcinogen-induced abnormalities in the colon mucosa.}, }
@article {pmid3121516, year = {1987}, author = {Heizmann, W and Ehninger, G and Vallbracht, A and Botzenhart, K}, title = {Surveillance cultures and benefit of laminar airflow units in patients undergoing bone marrow transplantation.}, journal = {Infection}, volume = {15}, number = {5}, pages = {337-343}, pmid = {3121516}, issn = {0300-8126}, mesh = {Adolescent ; Adult ; Bacteria, Aerobic/*growth &amp; development ; *Bone Marrow Transplantation ; Candida/isolation &amp; purification ; Child ; Child, Preschool ; Digestive System/microbiology ; *Environment, Controlled ; Feces/microbiology ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Pharynx/microbiology ; Pseudomonas aeruginosa/isolation &amp; purification ; Skin/microbiology ; Staphylococcus aureus/isolation &amp; purification ; }, abstract = {The effectiveness of gastrointestinal and topical decontamination, as well as isolation in laminar airflow (LAF) units were investigated in 20 patients. On a weekly basis, surveillance cultures were taken. Environmental controls were taken on the medical ward outside the two LAF units and from the LAF unit itself when being used by a patient. The use of LAF units seems to be of benefit in preventing exogenous infections, but there are two weak points in the isolation techniques: the opening of the tent (with a free entry into the tent itself) and the water delivery system. By using appropriate decontamination measures, it was possible to greatly reduce the number of bacteria and species of the normal flora in all regions with the exception of the oropharynx. Individual patients with oxacillin resistant coagulase-negative staphylococci and/or Candida albicans continued to show the presence of these organisms during this time. The detection of Clostridium difficile and/or its toxin B in eight patients at the beginning of the individual observation period was significant. Four out of 15 fever episodes were attributable to endogenous bacterial infections. Each of the causative organisms had been previously isolated in the surveillance cultures, thus the clinician was able to initiate a calculated antimicrobial therapy. As evident from the low incidence of infectious complications, gastrointestinal and topical decontamination of the skin as well as reverse isolation in LAF units are efficient protective measures for bone marrow transplant patients.}, }
@article {pmid3543199, year = {1986}, author = {Koopman, BJ and van der Molen, JC and Haagsma, EB and Huizenga, JR and Krom, RA and Nagel, GT and Gips, CH and Wolthers, BG}, title = {Measurements of prednisolone and some of its metabolites, in urine of patients after orthotopic liver transplantation, as a means of monitoring prednisolone absorption.}, journal = {Journal of clinical chemistry and clinical biochemistry. Zeitschrift fur klinische Chemie und klinische Biochemie}, volume = {24}, number = {11}, pages = {831-839}, doi = {10.1515/cclm.1986.24.11.831}, pmid = {3543199}, issn = {0340-076X}, mesh = {Adolescent ; Adult ; Biotransformation ; Child, Preschool ; Chromatography, Gas ; Fats/analysis ; Feces/analysis ; Female ; Humans ; Intestinal Absorption ; *Liver Transplantation ; Male ; Middle Aged ; Prednisolone/analogs &amp; derivatives/metabolism/*urine ; Prednisone/urine ; }, abstract = {In patients who had undergone orthotopic liver transplantation, malabsorption of prednisolone or increased metabolism of prednisolone was suspected. In order to rule out this possibility, urinary prednisolone, and some of its metabolites, viz prednisone and 6 beta-hydroxyprednisolone, were determined by means of a gas chromatographic assay. To evaluate this assay aliquots of a pooled urine from several of our patients were analysed in multiplicate (n = 10). Mean prednisone, prednisolone and 6 beta-hydroxyprednisolone concentrations of 1.9 mg/l, 6.3 mg/l and 4.1 mg/l, respectively, were found with the following respective day-to-day coefficients of variation: 12.3%, 5.2% and 5.3%. Amounts of prednisolone metabolites excreted in the urine of these patients were correlated with the ingested daily dose of prednisolone. It was concluded that overall absorption of prednisolone in these patients was adequate and not influenced by shortage of bile acids in the gastro-intestinal tract, or by steatorrhoea, both caused by external bile drainage. In addition there was no evidence for increased metabolism of prednisolone.}, }
@article {pmid3640591, year = {1986}, author = {Wingard, JR and Dick, J and Charache, P and Saral, R}, title = {Antibiotic-resistant bacteria in surveillance stool cultures of patients with prolonged neutropenia.}, journal = {Antimicrobial agents and chemotherapy}, volume = {30}, number = {3}, pages = {435-439}, pmid = {3640591}, issn = {0066-4804}, support = {CA-15396/CA/NCI NIH HHS/United States ; CAO-6973/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Agranulocytosis/*microbiology ; Aminoglycosides/pharmacology ; Anti-Bacterial Agents/*pharmacology ; Carbenicillin/pharmacology ; Child ; Child, Preschool ; Feces/*microbiology ; Humans ; Leukemia/complications ; Neutropenia/*microbiology ; Penicillin Resistance ; }, abstract = {The value of stool surveillance for antibiotic-resistant gram-negative bacteria was analyzed in 86 neutropenic bone marrow transplant patients. Twice-weekly specimens were inoculated onto culture medium containing gentamicin plus carbenicillin. The recovered organisms were identified to the species level and tested for antibiotic susceptibility. Forty-eight resistant organisms were recovered from 35 patients. Thirteen isolates persistently colonized patients. Escherichia coli (29%) and Pseudomonas aeruginosa (19%) were the most frequently recovered organisms. Although most organisms were recovered while patients were on antibiotics, 15 isolates, including eight of nine resistant P. aeruginosa, were detected before antibiotics were initiated. The duration of antibiotic use was longer for patients persistently colonized than for those not colonized (P = 0.03). Of the 15 resistant organisms which caused infection, 12 were detected in the surveillance cultures. Infections by antibiotic-resistant organisms occurred more frequently in patients colonized than in those not colonized (P = 0.006) and more frequently in patients persistently colonized than in those colonized only once (P = 0.01). The absence of colonization or persistent colonization correlated well with the absence of infection (negative predictive values of 94 and 91%, respectively).}, }
@article {pmid3765888, year = {1986}, author = {Holschneider, AM and Donhauser, G and Amano, S and Urban, R}, title = {[Animal experiment studies of free transplantation of striated muscles].}, journal = {Zeitschrift fur Kinderchirurgie : organ der Deutschen, der Schweizerischen und der Osterreichischen Gesellschaft fur Kinderchirurgie = Surgery in infancy and childhood}, volume = {41}, number = {4}, pages = {230-238}, doi = {10.1055/s-2008-1043349}, pmid = {3765888}, issn = {0174-3082}, mesh = {Animals ; Fecal Incontinence/*surgery ; Graft Survival ; Microsurgery/*methods ; Muscle Denervation ; Muscles/blood supply/innervation ; Rats ; Rats, Inbred Strains ; *Surgical Flaps ; Urinary Incontinence/*surgery ; }, abstract = {Heterotopic autologous muscle transplants of the left soleus muscle were performed in 39 Wistar rats. In analogy to the method described by Hakelius, the muscle was implanted into the bed of the contralateral superficial flexor muscle of the fingers with a varying prestretch of 0, 25 and 50% of its original length at rest. The animals were sacrificed postoperatively after 5, 10, 20, 40 and 60 days and their musculature examined. It was found that revascularisation and reneurotisation depended on the degree of prestretching applied. If prestretching amounted to 25 and 50%, complete degeneration of the connective tissue of the transplanted muscle occurred. However, even if prestretching was only low, i.e. between 0 and 5%, only one-third of the muscle mass regenerated and was interspersed with connective tissue of low cellular and vascular content with cicatrisation. These findings were also seen--to a lesser degree--if the soleus muscle was only denervated. We can conclude from this that restretching plays a decisive role even in the transplantation of striated muscle, as far as revascularisation and reneurotisation are concerned, and that even under the most favourable conditions only part of the transplanted muscle retains its full functional capacity. Furthermore, direct nerve anastomoses between the pudendal nerve and a branch of the femoral nerve supplying the transplanted semitendinous muscle, were performed in four Syrian goats. It was found that neurotisation of the muscle via microanastomosis is preferable to diffuse reneurotisation via the transplant bed. However, problems arose in respect of the blood supply of the transplanted semitendinous muscle, when using the technique after Holle and Freilinger.}, }
@article {pmid3738234, year = {1986}, author = {McKellar, Q and Duncan, JL and Armour, J and McWilliam, P}, title = {Response to transplanted adult Ostertagia ostertagi in calves.}, journal = {Research in veterinary science}, volume = {40}, number = {3}, pages = {367-371}, pmid = {3738234}, issn = {0034-5288}, mesh = {Animals ; Cattle ; Cattle Diseases/enzymology/*parasitology ; Feces/parasitology ; Ostertagiasis/enzymology/*veterinary ; Parasite Egg Count/veterinary ; Pepsinogens/*blood ; Trichostrongyloidiasis/*veterinary ; }, abstract = {Plasma pepsinogen levels became elevated in groups of recipient calves immediately after transplant with adult Ostertagia ostertagi. These rises occurred in both previously parasite-naive calves and in calves which had experienced prior infection terminated with an anthelmintic either seven or 21 days before transplant. From the results it appears that adult O ostertagi play a significant role in the elevated plasma pepsinogen levels associated with bovine ostertagiasis.}, }
@article {pmid3515722, year = {1986}, author = {Gittes, RF}, title = {Carcinogenesis in ureterosigmoidostomy.}, journal = {The Urologic clinics of North America}, volume = {13}, number = {2}, pages = {201-205}, pmid = {3515722}, issn = {0094-0143}, mesh = {Adenocarcinoma/*etiology ; Adult ; Animals ; Bladder Exstrophy/*surgery ; Child ; Colon, Sigmoid/surgery ; Colostomy ; Disease Models, Animal ; Female ; Humans ; Ileum/transplantation ; Intestinal Polyps/etiology ; Neoplasm Metastasis ; *Postoperative Complications ; Rats ; Rats, Inbred Strains ; Retrospective Studies ; Sigmoid Neoplasms/*etiology ; Time Factors ; Ureter/surgery ; Ureteral Neoplasms/*etiology ; *Urinary Diversion ; }, abstract = {Both clinical and experimental observations establish that an adenocarcinoma of the colon is likely to occur at the suture line of ureterosigmoidostomy. The carcinogenesis depends on the initial presence of urine, feces, urothelium, and colonic epithelium in close apposition at a healing suture line. It does not occur in isolated colon loops used for urinary diversion. In our rat model, tumors were completely prevented by interposing ileum between the urothelium and colon. Clinical prevention requires that accurate hospital registries of patients at risk be established and that repeated annual colonoscopy be carried out on all of them.}, }
@article {pmid3963715, year = {1986}, author = {Prochiantz, A}, title = {[A double operation for the repair of anal incontinence].}, journal = {Annales de pediatrie}, volume = {33}, number = {2}, pages = {141-145}, pmid = {3963715}, issn = {0066-2097}, mesh = {Anal Canal/*surgery ; Buttocks ; Fecal Incontinence/*surgery ; Humans ; Muscles/*transplantation ; }, }
@article {pmid3731367, year = {1986}, author = {Basset, D and Gaumerais, H and Basset-Pougnet, A}, title = {[Intestinal parasitoses in children of an Indian community of Bolivian altiplano].}, journal = {Bulletin de la Societe de pathologie exotique et de ses filiales}, volume = {79}, number = {2}, pages = {237-246}, pmid = {3731367}, mesh = {Adolescent ; Amebiasis/epidemiology ; Ascariasis/epidemiology ; Balantidiasis/epidemiology ; Bolivia ; Child ; Child, Preschool ; Dysentery, Amebic/epidemiology ; Endolimax ; Eukaryota ; Female ; Giardiasis/epidemiology ; Humans ; *Indians, South American ; Infant ; Intestinal Diseases, Parasitic/*epidemiology ; Male ; Oxyuriasis/epidemiology ; Protozoan Infections/epidemiology ; Taeniasis/epidemiology ; Trichuriasis/epidemiology ; }, abstract = {A survey about motion parasitosis has been carried out on one hundred Indians (Quechua ethnic group) living in a hamlet called Amarete located in the Bolivian Altiplano. This community is living in a place difficult to reach (11,100 feet) where many pre-Colombian traditions are still alive. All children were parasitized, 75% of them were carrier of 3 to 5 parasites. Infestation with ascaris (91%) is the most frequent and the risks of getting amebic dysentery (Entamoeba histolytica 41%) and balantidial (Balantidium coli 8%) are high. Many other parasites (8 kinds of protozoa , 5 kinds of helminths) can be observed; more especially, we noticed that 20% of the pupils used to be carrier operculated eggs. Tenia embryophores (more probably Taenia solium found in 2 children) made us aware of possibilities of cysticercosis. An other problem lays on general hygiene and hygiene of the water since feces danger is responsible of important parasitologic loads. Results are compared with a fecal study carried out on a population from the Altiplano region but living now in the plain. Amazonian Indian population in previous or recent contact with occidental civilization show the same variations of parasitologic repartition between Amarete hamlet and the transplanted population of Altiplano region. The role played by the acculturation could be discussed.}, }
@article {pmid3702238, year = {1986}, author = {Mal'tsev, VN and Kharishin, OM}, title = {[Surgical treatment of insufficiency of the anal sphincter].}, journal = {Klinicheskaia khirurgiia}, volume = {}, number = {2}, pages = {24-25}, pmid = {3702238}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/*surgery ; Buttocks ; Fecal Incontinence/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscles/transplantation ; Surgical Flaps ; }, }
@article {pmid3699065, year = {1986}, author = {Ogihara, I and Kojima, S and Jay, M}, title = {Tumor uptake of 67Ga-carrying liposomes.}, journal = {European journal of nuclear medicine}, volume = {11}, number = {10}, pages = {405-411}, pmid = {3699065}, issn = {0340-6997}, mesh = {Animals ; Carcinoma, Ehrlich Tumor/*diagnostic imaging ; *Gallium Radioisotopes ; Liposomes/*administration &amp; dosage ; Male ; Mice ; Neoplasm Transplantation ; Radionuclide Imaging ; Tissue Distribution ; }, abstract = {The in vivo distribution, excretion, and tumor localization of liposome-encapsulated 67Ga in normal and Ehrlich tumor (solid form)-bearing mice were studied. In normal mice, multilamellar vesicles (MLVs) were taken up mainly by the liver and spleen, whereas small unilamellar vesicles (SUVs) exhibited a broader tissue distribution. When 67Ga was encapsulated in MLVs or SUVs, the excretion of the radiotracer in the urine and feces was less than that observed for free tracer at 72 h after i.v. administration. In tumor-bearing mice, SUVs were found to accumulate preferentially in tumors. The tumor uptake of neutral, positive, and negative SUVs was 10%-13% of the administered dose per gram of tumor tissue at 24 h after their injection. These values were about three times higher than those found for free 67Ga-nitrilotriacetic acid (67Ga-NTA) or 67Ga-citrate. Significant differences in tumor uptake due to different surface charges of liposomes were not observed. Enhanced tumor-to-blood and tumor-to-muscle ratios were also observed at 24 h after injection. These results suggest that 67Ga-carrying liposomes may be a useful for tumor imaging.}, }
@article {pmid3545520, year = {1986}, author = {Gil-Vernet, HJ and Sanchis, SL}, title = {[Anorectal malformations. Striated muscle plasty].}, journal = {Chirurgie pediatrique}, volume = {27}, number = {5}, pages = {296-304}, pmid = {3545520}, issn = {0180-5738}, mesh = {Anus, Imperforate/surgery ; Fecal Incontinence/etiology/*surgery ; Humans ; Muscles/*transplantation ; Postoperative Complications/surgery ; }, }
@article {pmid3079996, year = {1986}, author = {Church, JM and Fazio, VW and Braun, WE and Novick, AC and Steinmuller, DR}, title = {Perforation of the colon in renal homograft recipients. A report of 11 cases and a review of the literature.}, journal = {Annals of surgery}, volume = {203}, number = {1}, pages = {69-76}, pmid = {3079996}, issn = {0003-4932}, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Diverticulum/complications ; Fecal Impaction/complications ; Female ; Humans ; Immunosuppression Therapy/adverse effects ; Intestinal Perforation/diagnosis/*etiology/mortality/prevention &amp; control/surgery ; Kidney Failure, Chronic/complications ; *Kidney Transplantation ; Male ; Middle Aged ; Mortality ; Transplantation, Homologous/adverse effects ; }, abstract = {Colon perforation in renal transplant recipients is a potentially lethal condition that is amenable to appropriate medical and surgical treatment. The 11 cases seen at the Cleveland Clinic (incidence 1.1% of all renal transplant patients) and previous reports in the literature have been reviewed. The pathogenesis is related to a high incidence of diverticular disease in patients with polycystic kidneys and/or chronic renal failure, the effects of long-term immunosuppression, and the transplant procedure itself. The high mortality of this condition (61% overall) is related to the effects of immunosuppression on the response to sepsis and the surgical procedure used. Mortality has fallen from 88% (1970-1974) to 53% (1975-1979), and there are indications that it is continuing to fall. All four cases operated on here since 1980 have survived, giving a total operative mortality of 2/6, and all have maintained excellent allograft function. A high clinical index of suspicion, prompt exteriorization of the perforated colon, reduction of immunosuppression to minimal levels, and effective antibiotic coverage have all contributed to the declining mortality.}, }
@article {pmid2941994, year = {1986}, author = {Skácel, V and Laichman, S}, title = {The internal obturator muscles functioning as the neosphincter of the anus (V). Neosphincter in short-term and long-term clinical evaluation.}, journal = {Acta Universitatis Palackianae Olomucensis Facultatis Medicae}, volume = {113}, number = {}, pages = {317-324}, pmid = {2941994}, issn = {0301-2514}, mesh = {Adolescent ; Adult ; Anal Canal/physiopathology/*surgery ; Child ; Fecal Incontinence/therapy ; Humans ; Male ; Muscles/physiopathology/*surgery/transplantation ; }, }
@article {pmid4064862, year = {1985}, author = {Iwai, N and Kaneda, H and Tsuto, T and Yanagihara, J and Takahashi, T}, title = {Objective assessment of anorectal function after sphincter reconstruction using the gluteus maximus muscle. Report of a case.}, journal = {Diseases of the colon and rectum}, volume = {28}, number = {12}, pages = {973-977}, doi = {10.1007/BF02554320}, pmid = {4064862}, issn = {0012-3706}, mesh = {Anal Canal/physiopathology/*surgery ; Child ; Electromyography ; Fecal Incontinence/physiopathology/*surgery ; Follow-Up Studies ; Humans ; Male ; Manometry ; Muscles/physiopathology/transplantation ; }, abstract = {Sphincter reconstruction using the gluteus maximus muscle was attempted in a 9-year-old boy who had been incontinent following surgery for the high type of anorectal malformation. Anorectal function following this procedure was assessed by anorectal manometry, defecogram, and electromyography. Postoperative function improved from Kelly 1 (poor) to Kelly 3 (fair). Adequate anorectal pressure difference and good voluntary contraction were documented one year after surgery. A defecogram one month postoperatively showed the presence of an empty segment which had not been noted before. Tonic activity at rest, which had not been present before, was found both one month and one year after surgery. These results indicate that the gluteus maximus muscle maintains some function as a newly created anorectal sphincter. In the present study, the patient was examined periodically for one year after surgery. Further follow-up studies are necessary.}, }
@article {pmid4041755, year = {1985}, author = {Corman, ML}, title = {Gracilis muscle transposition for anal incontinence: late results.}, journal = {The British journal of surgery}, volume = {72 Suppl}, number = {}, pages = {S21-2}, doi = {10.1002/bjs.1800721314}, pmid = {4041755}, issn = {0007-1323}, mesh = {Adult ; Anal Canal/*surgery ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Middle Aged ; Muscles/*transplantation ; Transplantation, Autologous ; }, }
@article {pmid3837237, year = {1985}, author = {Gil-Vernet Huguet, JM and Bardji Pascual, C and Odone, M and Boix Ochoa, J}, title = {[Biofeedback technic in incontinence in high ano-rectal atresia].}, journal = {La Pediatria medica e chirurgica : Medical and surgical pediatrics}, volume = {7}, number = {5}, pages = {709-713}, pmid = {3837237}, issn = {0391-5387}, mesh = {Adolescent ; Adult ; Anus, Imperforate/*rehabilitation/surgery ; *Biofeedback, Psychology ; Child ; Child, Preschool ; Defecation ; Fecal Incontinence/etiology/*rehabilitation ; Humans ; Time Factors ; }, abstract = {Authors have employed biofeedback in functional rehabilitation of fecal incontinence after surgical treatment of high anorectal atresia. 34 patients have treated with that technique, of whom 27 underwent an levator plasty and 7 a muscular transplant procedure using a gracilis sling. A four channels Recording connected with a Arhan catheter and a TV-monitor visible to the patient have been employed. After a period of time variable from case to case, all patients of the "levator plasty" group prolonged the "alert-time" to a socially acceptable value, and all the patients of the "gracilis transplant" group obtained a complete fecal continence.}, }
@article {pmid4073822, year = {1985}, author = {Liavåg, I and Aanestad, O}, title = {Fecal incontinence. Diagnosis and treatment.}, journal = {Annales de gastroenterologie et d'hepatologie}, volume = {21}, number = {4}, pages = {247-250}, pmid = {4073822}, issn = {0066-2070}, mesh = {Fecal Incontinence/*diagnosis/surgery/therapy ; Female ; Humans ; Male ; }, abstract = {This is a survey of fecal incontinence. The etiology is multifactorial. It may develop after traumatic lesion of the anal sphincters, neurological disorders, rectal prolapse or idiopathic. The treatment may be conservative including diet, drugs and sphincter exercise or consisting of suture of the sphincter, post anal repair, free autogenous muscle transplantation. In some cases colostomy is the only way of choice.}, }
@article {pmid3897955, year = {1985}, author = {Nawa, Y and Kiyota, M and Korenaga, M and Kotani, M}, title = {Defective protective capacity of W/Wv mice against Strongyloides ratti infection and its reconstitution with bone marrow cells.}, journal = {Parasite immunology}, volume = {7}, number = {4}, pages = {429-438}, doi = {10.1111/j.1365-3024.1985.tb00088.x}, pmid = {3897955}, issn = {0141-9838}, mesh = {Animals ; Bone Marrow Cells ; Bone Marrow Transplantation ; Feces/parasitology ; Mast Cells/*immunology ; Mice ; Mice, Mutant Strains/*immunology/parasitology ; Strongyloides ; Strongyloidiasis/*immunology ; }, abstract = {The susceptibility of congenitally anemic, and mast cell deficient W/Wv mice to infection with Strongyloides ratti was examined. After a primary infection, W/Wv mice showed greater and more persistent peak larval counts than did normal littermates. Worm expulsion was also slower in W/Wv mice than in +/+ mice. Furthermore, difference in susceptibility was expressed as early as 24 h after infection, suggesting not only that protective mechanisms of the gut but also of the connective tissue were defective in W/Wv mice. Reconstitution with bone marrow or spleen cells from +/+ mice was effective in restoring the protective response in W/Wv mice, whereas thymocytes or mesenteric lymph nodes had no effect. Both connective tissue and mucosal mast cells were repaired in W/Wv mice after marrow reconstitution and infection. Since relatively long incubation period was required for the expression of such reconstituting activities, bone marrow cells seem to contain precursor cells of the effector and/or regulator cells.}, }
@article {pmid4006578, year = {1985}, author = {Schmidt, E}, title = {[Late results following smooth muscle sphincter replacement].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {56}, number = {5}, pages = {305-310}, pmid = {4006578}, issn = {0009-4722}, mesh = {Adult ; Anal Canal/surgery ; Colostomy/*methods ; Fecal Incontinence/*surgery ; Female ; Follow-Up Studies ; Humans ; Muscle, Smooth/*transplantation ; Postoperative Care/methods ; Rectal Prolapse/*surgery ; Rectum/surgery ; }, }
@article {pmid3987480, year = {1985}, author = {Sidhu, GS and Narasimharao, KL and Usha Rani, V and Sarkar, AK and Mitra, SK}, title = {Absorption studies after massive small bowel resection and antiperistaltic colon interposition in rhesus monkeys.}, journal = {Digestive diseases and sciences}, volume = {30}, number = {5}, pages = {483-488}, pmid = {3987480}, issn = {0163-2116}, mesh = {Animals ; Barium Sulfate ; Carbohydrate Metabolism ; Colon/diagnostic imaging/*transplantation ; Fats/metabolism ; Feces/analysis ; *Gastrointestinal Motility ; *Intestinal Absorption ; Intestine, Small/diagnostic imaging/*surgery ; Macaca mulatta ; *Peristalsis ; Radiography ; Schilling Test ; Stomach/diagnostic imaging ; Time Factors ; Vitamin B 12/metabolism/urine ; Xylose/metabolism ; }, abstract = {An experimental model of massive (80%) small bowel resection and antiperistaltic colon interposition in between the remnant jejunum and ileum was created in rhesus monkeys. The gastrointestinal functions were assessed preoperatively and at different periods after the operation. Progressive increase in the transit time and enhanced absorption of D-xylose and vitamin B12 was observed in these animals. The transit time marginally increased till three months postoperatively, and a significant increase was observed later (4-12 months) in the colon autografted monkeys. After three months, the D-xylose absorption in the colon interpositioned animals was nearly equal to that of normal monkeys. There was no significant difference in the vitamin B12 absorption in the normal and operated animals up to three months, but a significant rise was observed in the latter group after this period. The fecal fat excretion was 33-44% initially, and it gradually decreased to near normal values after nine months. The antiperistaltic colon interposition was effective in improving the early postoperative survival in animals after massive small bowel resection and enhanced the bowel absorption considerably.}, }
@article {pmid4009359, year = {1985}, author = {Hofmann-von Kap-herr, S and Koltai, IL and Tennant, LJ}, title = {Anal sphincter substitute using autologous smooth muscle in a fold-over, half-cylinder, double plasty (SMFD-plasty): a new method of treatment of anorectal incontinence.}, journal = {Journal of pediatric surgery}, volume = {20}, number = {2}, pages = {134-137}, doi = {10.1016/s0022-3468(85)80285-2}, pmid = {4009359}, issn = {0022-3468}, mesh = {Anal Canal/abnormalities/physiology/*surgery ; Child ; Child, Preschool ; Fecal Incontinence/*surgery ; Humans ; Infant ; Infant, Newborn ; Manometry ; Methods ; Muscle, Smooth/*transplantation ; Rectum/abnormalities ; }, abstract = {A new operative procedure for improving continence is presented. It is used in patients with intermediate and high types of anorectal anomalies. A smooth muscle fold-over half-cylinder double plasty (SMFD-Plasty) is performed in infants immediately following the pull-through which must be done exactly through the puborectal sling. Results in six neonates and 4 older children so far are excellent. This method is a suitable replacement, particularly for the function of the internal sphincter. Further modifications of this new method are presented. They are recommended for secondary surgery (second pull-through, levator plasty, secondary megacolon, and post pull-through anal prolapse) as well as a primary procedure for continence improvement in patients treated according to the posterior method of Pena and de Vries.}, }
@article {pmid3996099, year = {1985}, author = {Köle, W and Ornig, H and Zmugg, P}, title = {[Transabdominal circumrectal use of Schmidt-plasty with free transplanted autologous intestinal musculature in complete anal sphincter incontinence].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {56}, number = {4}, pages = {276-279}, pmid = {3996099}, issn = {0009-4722}, mesh = {Adult ; Anal Canal/injuries/*surgery ; Anus, Imperforate/surgery ; Colon, Sigmoid/transplantation ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Manometry ; Muscle Contraction ; Muscle, Smooth/*transplantation ; Postoperative Complications/diagnostic imaging/surgery ; Radiography ; Rectum/injuries ; }, }
@article {pmid3885487, year = {1985}, author = {Moffat, FL and Falk, RE and Teodorczyk-Injeyan, J and Clark, AG and Gilas, T and Falk, M and Dalfen, R and Rotstein, LE and McDonell, M and Makowka, L}, title = {Reversal of cyclosporine-induced mortality with a synthetic polymeric immunostimulant in a murine model of fecal peritonitis.}, journal = {Transplantation}, volume = {39}, number = {4}, pages = {369-374}, doi = {10.1097/00007890-198504000-00006}, pmid = {3885487}, issn = {0041-1337}, mesh = {Animals ; Carbamates/*pharmacology ; Cyclosporins/administration &amp; dosage/*adverse effects ; Graft Survival/drug effects ; Ligation ; Male ; Mice ; Mice, Inbred CBA ; Peritonitis/*chemically induced ; Povidone/*pharmacology ; Skin Transplantation ; Time Factors ; }, abstract = {We have been investigating the effects of a synthetic immunostimulative polymer known as copovithane (Cpv). This agent appears to enhance humoral immunity in untreated and cyclosporine-immunosuppressed mice and is nontoxic in rodents and man. The purpose of this study was to determine whether cyclosporine (CsA) is deleterious to survival in a murine cecal ligation, puncture, and excision (CLPE) model of fecal peritonitis, and--if so--whether this effect could be ameliorated by Cpv without interfering with skin allograft acceptance. Cpv significantly prolongs survival in the CLPE model; the optimal dose for this effect was found to be 100 mg/kg. CsA was found to have a significant and deleterious effect on survival at several dosage levels when administrated 48 and 24 hr before cecal ligation, and immediately before and 16 hr after cecal ligation. Using a dose of CsA sufficient for skin allograft acceptance and the same schedule of administration outlined above, Cpv 100 mg/kg was administered 48 hr prior to cecal ligation. Mice treated with CsA plus Cpv had significantly longer survival than mice treated with CsA alone; furthermore, the survival of CsA-plus-Cpv-treated animals was not significantly different from that of saline-treated controls. Acceptance and survival of H-2 incompatible skin allografts in mice treated with CsA were not affected by Cpv 100 mg/kg/week. We conclude that CsA-induced mortality in the CLPE model can be abrogated by Cpv without adversely affecting skin allograft survival. It may eventually be possible to reduce the incidence of septic complications in clinical allotransplantation by prophylactically administering Cpv to patients on CsA immunosuppression.}, }
@article {pmid3883760, year = {1985}, author = {Hoy, WE and Sargent, JA and Hall, D and McKenna, BA and Pabico, RC and Freeman, RB and Yarger, JM and Byer, BM}, title = {Protein catabolism during the postoperative course after renal transplantation.}, journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation}, volume = {5}, number = {3}, pages = {186-190}, doi = {10.1016/s0272-6386(85)80049-4}, pmid = {3883760}, issn = {0272-6386}, mesh = {Adolescent ; Adult ; Aged ; Dietary Proteins/metabolism ; Feces/analysis ; Female ; Glucocorticoids/therapeutic use ; Graft Rejection ; Humans ; *Kidney Transplantation ; Male ; Middle Aged ; Postoperative Period ; Proteins/*metabolism ; Time Factors ; }, abstract = {Protein catabolic rate (PCR) was measured daily by computerized mass balance studies in 50 subjects during hospitalization after renal transplant. All subjects received 60 mg prednisone per day. PCR rose over the first 3 to 4 postoperative days and then stabilized at an accelerated level, which was sustained through the third posttransplant week. Rejection therapy with either 3 mg/kg/d prednisone or 15 mg/kg/d of methylprednisolone for 3 days further increased PCR, but there was no difference in PCR between these two regimens. Protein restriction did not decrease PCR and subjects offered a higher protein diet did not have further acceleration of PCR. We conclude that 60 mg/kg/d prednisone produces an obligatory acceleration of PCR that is further accentuated by higher steroid doses. The use of minimal maintenance doses of prednisone consistent with adequate immunosuppression seems wise. Protein balance may be improved if protein intake is increased to match individual rates of accelerated protein catabolism.}, }
@article {pmid3887619, year = {1985}, author = {Schoetz, DJ}, title = {Operative therapy for anal incontinence.}, journal = {The Surgical clinics of North America}, volume = {65}, number = {1}, pages = {35-46}, doi = {10.1016/s0039-6109(16)43531-0}, pmid = {3887619}, issn = {0039-6109}, mesh = {Anal Canal/physiopathology/*surgery ; Fecal Incontinence/diagnosis/physiopathology/*surgery/therapy ; Female ; Humans ; Manometry ; Muscles/transplantation ; Postoperative Care ; Suture Techniques ; }, abstract = {Operative therapy for fecal incontinence requires exact understanding of the anatomic and physiologic principles involved and of the potential pathophysiologic mechanisms. Many injuries of the external sphincter can be treated by direct sphincter repair. Extensive obstetric injuries with loss of the perineal body require not only reconstitution of the perineal musculature but also plastic surgical reconstruction of the perineal skin. Patients with descending perineum syndrome and resultant idiopathic fecal incontinence or rectal prolapse with associated incontinence should be treated with postanal plication of the puborectalis sling. Patients who have complex neurologic disorders or who have undergone previous unsuccessful attempts at repair of the puborectalis itself should be considered for placement of a Silastic sling. Diverting colostomy is rarely necessary; it should be performed only after thorough investigation and failure of all reasonable alternative operative procedures.}, }
@article {pmid4072469, year = {1985}, author = {Kirchner, H and Kiene, S and Festge, OA}, title = {[Manometry studies of continence performance in patients following gracilisplasty].}, journal = {Zentralblatt fur Chirurgie}, volume = {110}, number = {20}, pages = {1258-1262}, pmid = {4072469}, issn = {0044-409X}, mesh = {Adolescent ; Adult ; Aged ; Fecal Incontinence/diagnosis/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Manometry ; Middle Aged ; Muscle Tonus ; Muscles/*transplantation ; Postoperative Complications/diagnosis ; }, abstract = {Out of a total of 10 patients who had undergone a Pickrell-procedure of the gracilis muscle from 1970-1980, 6 were now followed-up by clinical examination and perfusion manometry of the anal canal. The manometric parameters were compared with an anamnestic score. For anal continence the degree of resting activity of the transposed gracilis muscle is in our opinion not decisive. For that reason, there is no necessity for a permanent contraction.}, }
@article {pmid3984649, year = {1985}, author = {Schrøder, HM and Hovendal, C}, title = {Salmonella sepsis following posttraumatic splenectomy and implantation of autologous splenic tissue.}, journal = {Acta chirurgica Scandinavica}, volume = {151}, number = {1}, pages = {11-12}, pmid = {3984649}, issn = {0001-5482}, mesh = {Humans ; Male ; Middle Aged ; Postoperative Complications ; Reoperation ; Salmonella Infections/*etiology/therapy ; Sepsis/*etiology/therapy ; Spleen/*transplantation ; Splenectomy/*adverse effects ; Splenic Artery/injuries ; Transplantation, Autologous/*adverse effects ; }, abstract = {A severe complication following implantation of autologous splenic tissue occurred in a 51-year-old man. Indirect injury to abdomen resulted in a lesion of the splenic artery. Following splenectomy and reimplantation of splenic tissue into three pouches, a severe Salmonella sepsis developed within 24 hours. At second look laparotomy two pouches were infected. Recently there had been moderate signs of gastroenteritis and the same bacteria was cultivated from feces. Modifications of the implantation procedure are discussed.}, }
@article {pmid3971793, year = {1985}, author = {Leguit, P and van Baal, JG and Brummelkamp, WH}, title = {Gracilis muscle transposition in the treatment of fecal incontinence. Long-term follow-up and evaluation of anal pressure recordings.}, journal = {Diseases of the colon and rectum}, volume = {28}, number = {1}, pages = {1-4}, doi = {10.1007/BF02553893}, pmid = {3971793}, issn = {0012-3706}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/physiopathology ; Child ; Fecal Incontinence/etiology/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscles/*transplantation ; Postoperative Complications ; Pressure ; Time Factors ; }, abstract = {The results after gracilis muscle transposition were studied in ten patients with a follow-up of six months to 17 years. Nine patients were continent for formed feces and the condition of one patient worsened after operation. Anorectal manometry was performed in eight of the ten patients. Evaluation of pressure recordings showed a normal image, both at rest and at maximal squeeze, in five patients. Low-pressure recordings at rest and at maximal squeeze were seen in two continent patients, in whom the tissue scarring resulted in narrowing of the anal canal. One patient with low-pressure recordings was completely incontinent. An attempt was made to explain the continence and low-pressure recordings. The results suggest gracilis muscle transposition to be a method of choice in patients with total incontinence who have no functional and sphincter.}, }
@article {pmid3840552, year = {1985}, author = {Hansen, H}, title = {[Replacement of the rectal ampulla].}, journal = {Langenbecks Archiv fur Chirurgie}, volume = {366}, number = {}, pages = {273-277}, pmid = {3840552}, issn = {0023-8236}, mesh = {Colectomy ; Colon/surgery ; Fecal Incontinence/surgery ; Female ; Hirschsprung Disease/surgery ; Humans ; Ileum/transplantation ; Intestinal Polyps/surgery ; Postoperative Complications/surgery ; Rectal Diseases/*surgery ; Rectal Neoplasms/surgery ; Rectovaginal Fistula/surgery ; Rectum/surgery ; }, abstract = {In ulcerative colitis, polyposis coli, deep seated cancer and other diseases of the rectum the bowel continuity can be restored without loss of continence, despite the removal of the entire ampulla recti. After proctocolectomy and ileoanostomy the loss of the natural receptaculum is compensated through the positioning of an ileal pouch. After total resection of the rectum and coloanal anostomosis the excised ampulla is replaced with acceptable functional results by the mobilised left colon.}, }
@article {pmid6394620, year = {1984}, author = {Smith, JA and Sherlock, CH and Burdge, DR}, title = {Feasible method for routine surveillance culturing of stools from neutropenic patients.}, journal = {Journal of clinical microbiology}, volume = {20}, number = {6}, pages = {1174-1176}, pmid = {6394620}, issn = {0095-1137}, mesh = {Agranulocytosis/*microbiology ; Bacteria/*isolation &amp; purification ; *Bacteriological Techniques ; Drug Resistance, Microbial ; Feces/*microbiology ; Humans ; Microbial Sensitivity Tests ; Neutropenia/*microbiology ; }, abstract = {This study was undertaken to develop an accurate, yet inexpensive, method for determining whether the bowel of a neutropenic patient is colonized with bacteria resistant to the antimicrobial agents used in empiric therapy. Selective agar media were prepared in which Mueller-Hinton agar or MacConkey agar were supplemented with one of the following antimicrobial agents: carbenicillin (16 micrograms/ml), gentamicin (4 micrograms/ml), or tobramycin (4 micrograms/ml). Moxalactam was incorporated initially at 16 micrograms/ml and subsequently at 8 micrograms/ml. Stools from neutropenic patients and bone marrow transplant recipients were inoculated on these media and on unsupplemented MacConkey agar. All bacteria that grew on the antibiotic-containing media were categorized as resistant to the supplementing drug; failure to detect an organism that did grow on the antibiotic-free MacConkey agar indicated susceptibility. These results were compared with those obtained for all isolates on all media by agar disk diffusion. There were 512 gram-negative enteric isolates from 320 stools obtained from 98 patients. The antibiotic-containing media suppressed the growth of 95% of bacteria that were identified as susceptible by agar disk diffusion. In detecting resistant organisms, the correlation between agar disk diffusion and direct stool screening with Mueller-Hinton agar ranged from 73 to 83%, and on MacConkey agar it ranged from 87 to 97%. The predictive value of a resistant result was 80 to 97% for the four antimicrobial agents when MacConkey agar was used. MacConkey agar performed better than Mueller-Hinton agar because of the greater ease of detecting different bacterial morphotypes. The cost of direct stool screening with antibiotic-supplemented MacConkey agar is approximately half the cost of routine methods of surveillance. Its cost and accuracy make the method a useful adjunct to the routine management of neutropenic patients.}, }
@article {pmid6387000, year = {1984}, author = {Wells, CL and Podzorski, RP and Peterson, PK and Ramsay, NK and Simmons, RL and Rhame, FS}, title = {Incidence of trimethoprim-sulfamethoxazole-resistant enterobacteriaceae among transplant recipients.}, journal = {The Journal of infectious diseases}, volume = {150}, number = {5}, pages = {699-706}, doi = {10.1093/infdis/150.5.699}, pmid = {6387000}, issn = {0022-1899}, mesh = {*Bone Marrow Transplantation ; Citrobacter/drug effects/isolation &amp; purification ; Drug Combinations/pharmacology/therapeutic use ; Drug Resistance, Microbial ; Enterobacteriaceae/*drug effects/isolation &amp; purification ; Escherichia coli/drug effects/isolation &amp; purification/metabolism ; Escherichia coli Infections/microbiology ; Feces/*microbiology ; Humans ; *Kidney Transplantation ; *Pancreas Transplantation ; Sepsis/microbiology ; Sulfamethoxazole/*pharmacology/therapeutic use ; Thymidine/pharmacology ; Trimethoprim/*pharmacology/therapeutic use ; Trimethoprim, Sulfamethoxazole Drug Combination ; }, abstract = {Of 114 recipients of pancreatic, renal, and bone marrow transplants who were given trimethoprim-sulfamethoxazole (TMP-SMZ) for antimicrobial prophylaxis, 44 (39%) had a total of 52 fecal isolates of TMP-SMZ-resistant gram-negative bacilli. In most of these 44 patients, the resistant isolate was found at a concentration of greater than or equal to 10(6) organisms/ml of feces. Escherichia coli was the most frequent of the isolates, and Citrobacter freundii was the next most frequent. Eight of the 114 transplant recipients had gram-negative bacteremia; in six of these eight patients, a TMP-SMZ-resistant gram-negative bacillus was the etiologic agent of bacteremia. Four of the latter six patients had stool cultures analyzed prior to the detection of bacteremia; all four had high concentrations (greater than or equal to 10(8)/ml) of fecal TMP-SMZ-resistant E. coli one to 20 days before they were found to have E. coli bacteremia. In each of these instances, the E. coli isolates from the stool and the blood had similar antibiograms. These findings indicated that resistance to TMP-SMZ is becoming more prevalent and that the screening of patients for the presence of fecal TMP-SMZ-resistant Enterobacteriaceae prior to initiation of long-term therapy with this antimicrobial agent may be worthwhile.}, }
@article {pmid6099088, year = {1984}, author = {Dufourmentel, C and Petoin, DS}, title = {[Reconstructive surgery of the anoperineal region].}, journal = {Annales de gastroenterologie et d'hepatologie}, volume = {20}, number = {5}, pages = {249-257}, pmid = {6099088}, issn = {0066-2070}, mesh = {Anal Canal/*surgery ; Anus Diseases/surgery ; Bowen's Disease/surgery ; Burns/surgery ; Fecal Incontinence/surgery ; Humans ; Inflammation ; Paget Disease, Extramammary/surgery ; Perineum/injuries/*surgery ; Radiodermatitis/surgery ; Skin Neoplasms/surgery ; Skin Transplantation ; *Surgery, Plastic ; Surgical Flaps ; Sweat Gland Diseases/surgery ; }, abstract = {The embryology and anatomy of the ano-perineal region explain the complex pathology which is difficult to treat. Six types of lesions are discussed. Congenital skin lesions: naevus or angiomas, requiring the same procedures of local autoplasty and graft as those of other regions, whenever they are extensive. Infectious lesions are dominated by Verneuil's disease, chronic hidradenitis or acne conglobata. Treatment involves wide excision which is sufficiently deep, followed by skin graft. Cancerous or pre-cancerous lesions. A distinction must be made between Bowen's disease and Paget's disease: the first is a precancerous lesion and the second is a sign of underlying carcinoma. The treatment is very different for the two conditions. Radiation dermatitis is not exceptional. Surgical treatment is required, but it is difficult. Radio-necroses can be repaired with epiplooplasty and a musculo-cutaneous flap from gluteus maximus. Post-traumatic and surgical sequelae sometimes need to be repaired by a plastic operation. Anal continence can be treated by surgical repair.}, }
@article {pmid6532709, year = {1984}, author = {Liu, GL}, title = {[Free autogenous skeletal muscle transplantation for anal incontinence in children--animal experiment and clinical application].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {22}, number = {9}, pages = {519-21, 572}, pmid = {6532709}, issn = {0529-5815}, mesh = {Animals ; Child ; Child, Preschool ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Muscles/*transplantation ; Rabbits ; }, }
@article {pmid6378005, year = {1984}, author = {Collier, AC and Miller, RA and Meyers, JD}, title = {Cryptosporidiosis after marrow transplantation: person-to-person transmission and treatment with spiramycin.}, journal = {Annals of internal medicine}, volume = {101}, number = {2}, pages = {205-206}, doi = {10.7326/0003-4819-101-2-205}, pmid = {6378005}, issn = {0003-4819}, support = {AI 07044/AI/NIAID NIH HHS/United States ; CA 18029/CA/NCI NIH HHS/United States ; CA 30924/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; *Bone Marrow Transplantation ; Child, Preschool ; Coccidiosis/drug therapy/genetics/*transmission ; Feces/parasitology ; Female ; Humans ; Infant ; Intestinal Diseases, Parasitic/drug therapy/genetics/transmission ; Leucomycins/*therapeutic use ; Leukemia, Myeloid, Acute/therapy ; Postoperative Complications ; }, }
@article {pmid6378004, year = {1984}, author = {Portnoy, D and Whiteside, ME and Buckley, E and MacLeod, CL}, title = {Treatment of intestinal cryptosporidiosis with spiramycin.}, journal = {Annals of internal medicine}, volume = {101}, number = {2}, pages = {202-204}, doi = {10.7326/0003-4819-101-2-202}, pmid = {6378004}, issn = {0003-4819}, mesh = {Acquired Immunodeficiency Syndrome/complications ; Adult ; Bone Marrow Transplantation ; Child, Preschool ; Coccidiosis/*drug therapy/etiology ; Diarrhea/etiology/therapy ; Feces/parasitology ; Female ; Humans ; Intestinal Diseases, Parasitic/*drug therapy/etiology/parasitology ; Jejunum/parasitology ; Leucomycins/*therapeutic use ; Male ; Middle Aged ; Postoperative Complications ; }, abstract = {Nine male patients with the acquired immunodeficiency syndrome and one female patient who had an allogeneic bone marrow transplant for acute myeloblastic leukemia in relapse developed severe debilitating diarrhea. Cryptosporidium species were found in the stools of all patients. After receiving treatment with spiramycin for 1 week, five patients had complete resolution of the diarrhea and four patients had symptomatic improvement. One patient responded gradually and the diarrhea resolved after 30 days of treatment with spiramycin.}, }
@article {pmid6464563, year = {1984}, author = {Holschneider, AM and Amano, S and Urban, A and Donhauser, G}, title = {[Animal experimental studies on the free transplantation of smooth colon muscles as an artificial sphincter in the rat].}, journal = {Zeitschrift fur Kinderchirurgie : organ der Deutschen, der Schweizerischen und der Osterreichischen Gesellschaft fur Kinderchirurgie = Surgery in infancy and childhood}, volume = {39}, number = {3}, pages = {182-190}, doi = {10.1055/s-2008-1044206}, pmid = {6464563}, issn = {0174-3082}, mesh = {Anal Canal/physiopathology/*surgery ; Animals ; *Colon/pathology ; Constipation/epidemiology ; Fecal Incontinence/*surgery ; Intestinal Obstruction/epidemiology ; Manometry ; Muscle, Smooth/pathology/*transplantation ; Necrosis ; Postoperative Complications/epidemiology ; Rats ; Rats, Inbred Strains ; Transplantation, Autologous ; }, abstract = {Free autologous muscle transplants were performed on 59 Wistar rats of 70 to 90 days of age according to the method described by Schmidt (1978). The free smooth muscular transplant was prestretched by 0%, 100%, 120%, 150% and 200% and the animals were sacrificed on the 5th, 10th, 20th, 40th and 60th postoperative day, respectively. Five animals died postoperatively, of these three during ileus and stenosis after more than 150% prestretching of the transplant. Complications occurred in eleven further animals, which included again ileus phenomena nine times due to stenosing or disturbance of defecation, also as a result of obstruction phenomena. Complications always occurred in animals with more than 150% transplant prestretching. No relaxation reflex was observed manometrically in any of the transplants. Budding of nerve fibres also did not occur in any of the cases, neither from the plexus myentericus of the inner intestinal wall nor from outside. Histology revealed already after five days' survival leucocytous infiltration and connective tissue multiplication which increased with increasing prestretching of the transplant and longer survival time of the animals until complete metaplasia of the connective tissue. In preparations with 100 up to 120% prestretch not more than 20% of the original muscular mass was preserved. With prestretching of 150% and more the transplant underwent complete fibrosis. On the basis of these studies we must discourage performance of free transplants of smooth-muscle colon segments in newborn and young infants.}, }
@article {pmid6370635, year = {1984}, author = {Freeman, NV}, title = {The foreskin anoplasty.}, journal = {Diseases of the colon and rectum}, volume = {27}, number = {5}, pages = {309-313}, doi = {10.1007/BF02555638}, pmid = {6370635}, issn = {0012-3706}, mesh = {Anal Canal/*surgery ; Anus, Imperforate/surgery ; Child ; Child, Preschool ; Circumcision, Male ; Colon/surgery ; Humans ; Infant ; Male ; Methods ; Penis/*surgery ; Rectal Prolapse/surgery ; *Skin Transplantation ; }, abstract = {The role of anal sensation in fecal control is well established. A new operative method of creating a skin-lined anal canal using the patient's foreskin, as a secondary procedure, in patients with anal (colonic) prolapse following surgery for high anorectal anomalies, is described. The results in five patients treated between 1967 and 1979 are presented. A sixth patient, treated in 1983, is not included due to the short follow-up period.}, }
@article {pmid6373468, year = {1984}, author = {Reifenrath, WG and Chellquist, EM and Shipwash, EA and Jederberg, WW}, title = {Evaluation of animal models for predicting skin penetration in man.}, journal = {Fundamental and applied toxicology : official journal of the Society of Toxicology}, volume = {4}, number = {2 Pt 2}, pages = {S224-30}, doi = {10.1016/0272-0590(84)90156-8}, pmid = {6373468}, issn = {0272-0590}, mesh = {Animals ; Dogs ; Female ; Humans ; In Vitro Techniques ; Isoflurophate/metabolism ; Male ; Malonates/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Models, Biological ; *Skin Absorption ; Skin Transplantation ; Species Specificity ; Swine ; Thymus Gland/physiology ; }, abstract = {The human skin grafted athymic nude mouse, pig skin grafted athymic nude mouse, hairless dog, and weanling Yorkshire pig were evaluated as models for predicting skin penetration in man. Nine radiolabeled compounds previously tested on man were applied topically (4 micrograms/cm2) to each animal. These compounds included caffeine, benzoic acid, N,N-diethyl-m-toluamide, three steroids, and three insecticides. To correct for incomplete excretion of the label following topical absorption, percentage penetration was calculated by dividing the percentage of the topically applied radioactive dose recovered in the excreta by the corresponding percentage after parenteral administration and multiplication by 100. In the case of the grafted athymic nude mouse, calculated values of percentage penetration were confirmed because significant correlations (r = 0.78 for the human skin grafted athymic nude mouse and r = 0.97 for the pig skin grafted athymic nude mouse) were found between the calculated values and percentage penetration determined by summing radioactivity recovered in the urine, feces, tissues, and carcass. The results revealed a significant correlation between human skin grafted athymic nude mouse values and human values (r = 0.74, p = 0.05), and between weanling Yorkshire pig values and human values (r = 0.83, p = 0.05). In contrast, no significant correlation existed between human values and those of the hairless dog and pig skin grafted athymic nude mouse. The disposition of radioactivity following topical application of the radiolabeled nerve agent analog (diisopropylfluorophosphonate) and simulant (diethyl malonate) was determined in the weanling pig and the human skin grafted athymic nude mouse.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid6727890, year = {1984}, author = {Hecker, WC and Holschneider, AM and Schimmel, K}, title = {[Treatment results following the pull-through operation and continence-improving operations in high anal and rectum atresia].}, journal = {Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde}, volume = {132}, number = {3}, pages = {173-179}, pmid = {6727890}, issn = {0026-9298}, mesh = {Adolescent ; Adult ; Anus, Imperforate/*surgery ; Child ; Child, Preschool ; Fecal Incontinence/*prevention &amp; control ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Intestinal Atresia/*surgery ; Male ; Postoperative Complications/prevention &amp; control/surgery ; Rectum/*abnormalities ; Surgical Flaps ; }, abstract = {Of 174 patients with anorectal malformations, among them 71 children with high atresia, 59 patients could be followed-up. 57% were entirely incontinent according to electromanometrical findings. These patients necessarily needed sphincter-replacement operations to improve the function of the sphincter-apparatus. Eighty-one sphincter-replacement operations were performed in 68 patients, among them 56 gracilis transplantations, 12 palmaris-longus transplantations, and 4 stalked smooth muscle transplantations. All sphincter replacement operations improved continence considerably.}, }
@article {pmid6711814, year = {1984}, author = {Køppen, B and Dalgaard, L}, title = {Assay for beta-glucuronidase utilizing headspace gas chromatography.}, journal = {Analytical biochemistry}, volume = {136}, number = {1}, pages = {272-275}, doi = {10.1016/0003-2697(84)90335-x}, pmid = {6711814}, issn = {0003-2697}, mesh = {Animals ; Chromatography, Gas/methods ; Feces/analysis ; Glucuronidase/*analysis ; Humans ; Male ; Mammary Neoplasms, Experimental/enzymology ; Mice ; Mice, Nude ; Muscles/enzymology ; Neoplasm Transplantation ; Rats ; Rats, Inbred Strains ; }, abstract = {An assay for beta-glucuronidase is described. The assay uses 1-(beta-D-glucopyranuronosyl)pyridinium hydroxide, inner salt, as substrate and the quantitative determination is performed with headspace gas chromatography, measuring one of the products, pyridine, in the gas phase. The assay has been developed utilizing commercially available beta-glucuronidase (EC 3.2.1.31.) from Escherichia coli, and has been applied to various sources of beta-glucuronidase. Crude homogenates can be assayed directly with a minimum of manipulative steps and the method is suited for automation.}, }
@article {pmid6711169, year = {1984}, author = {Tischer, W and Festge, OA}, title = {[Clinical course and therapy of fecal incontinence in children].}, journal = {Zentralblatt fur Chirurgie}, volume = {109}, number = {4}, pages = {236-244}, pmid = {6711169}, issn = {0044-409X}, mesh = {Age Factors ; Biofeedback, Psychology ; Child ; *Fecal Incontinence/diagnosis/surgery ; Humans ; Muscles/transplantation ; }, abstract = {Among the operative techniques for correction of anal incontinence the transplantation of small striated muscles, which has to be denervated before, is hopeful. In the conservative treatment biofeedback techniques are of great interest. New diagnostic procedures (combined manometric and electromyographic readings of the anal sphincter pressure) allow a better understanding of the individual type of anal incontinence. There are a lot of technical proposals aimed at overcoming anal incontinence. Among them the free transplantation of autogenous muscle can be regarded as a step in the forward direction. As far as conservative treatment is concerned the biofeedback treatment seems to be of interest.}, }
@article {pmid6518612, year = {1984}, author = {Mollard, P}, title = {[Upper anal imperforation, treatment and results].}, journal = {Chirurgie pediatrique}, volume = {25}, number = {6}, pages = {305-310}, pmid = {6518612}, issn = {0180-5738}, mesh = {Abnormalities, Multiple/surgery ; Adult ; Anus, Imperforate/*surgery ; Colostomy ; Fecal Incontinence/surgery ; Female ; Humans ; Infant, Newborn ; Male ; Methods ; Postoperative Complications ; Reoperation ; }, abstract = {As shown by Stephens the only element of the sphincteric mechanism which persists in case of high imperforate anus is the pubo rectalis sling of the levator. It is essential that the néo rectum be brought down to the perineum throught the sling which must be meticulously dissected and preserved. An operative technique with definition of the sling by an anterior perineal approach was described by the author. Results of the procedure in 43 patients are reported: early post operative complications (1 death, 4 occlusions, 2 ischemia of the neo rectum), anal complications (stricture, prolapses and ectropion) and urinary complications. Concerning the continence the author studied 19 patients: 16 children operated over 10 years ago and 3 adults. Of these 19: 2 are failures with stool incontinence, 10 are excellent and 7 fair. A "perfect" result was never obtained but many are compatible with a normal social life. Age is of great importance (our 3 adults became continent within several months), morning evacuations, diet, cleanliners, some drugs such a imodium are helpful adjuncts. Then the paper discusses 16 patients with desastrous results after previous surgery in another hospital. In 10 patients the new ano-rectum has been placed some that it missed a portion or all of the pubo-rectalis muscule. A further operation with re-routing resulted in marked improvement in 7 patients. A poor result with the neo-rectum in a good position means that the incontinence is related to a hypoplastic or denervated sling. A free autogenous muscle transplantation (Hakelius and Grotte) gave 4 excellent, 2 fair and 2 poor results.}, }
@article {pmid6475357, year = {1984}, author = {Kiene, S and Festge, OA and Maskow, G and Kirchner, H}, title = {[Clinical course and therapy of acquired anal incontinence].}, journal = {Zentralblatt fur Chirurgie}, volume = {109}, number = {12}, pages = {809-818}, pmid = {6475357}, issn = {0044-409X}, mesh = {Adult ; Anal Canal/*surgery ; Fecal Incontinence/etiology/*surgery ; Female ; Gastrointestinal Motility ; Humans ; Male ; Manometry ; Middle Aged ; Rectal Fistula/complications/surgery ; }, abstract = {43 patients suffering from anal incontinence underwent surgical correction. The late results up to 14 years after surgery are described. Continence was evaluated by inquiries and by manometric readings of the recto-anal stress profile. Prevailing surgical procedures were reconstruction of the anal sphincter (n = 23) and pedicled transplantation of the M. gracilis (n = 10). Both methods yielded satisfactory late results.}, }
@article {pmid6471993, year = {1984}, author = {Braun, J and Raguse, T and Hartung, R}, title = {[An elastic ileostomy sphincter using an autologous small intestine muscle flap].}, journal = {Langenbecks Archiv fur Chirurgie}, volume = {362}, number = {3}, pages = {193-204}, pmid = {6471993}, issn = {0023-8236}, mesh = {Animals ; Dogs ; Electromyography ; Fecal Incontinence/prevention &amp; control ; Ileostomy/*methods ; Intestine, Small ; Manometry ; Muscle, Smooth/blood supply/innervation/transplantation ; *Surgical Flaps ; }, abstract = {To achieve continence in ileostomies by free transplantation of small intestinal smooth muscle according to Schmidt failed frequently because of hemorrhagic necrosis of this graft. To safeguard intact vascularisation of the transplant flapped intestinal smooth muscle was used therefore in 15 dogs with ileostomy for sphincter replacements. Contrary to free grafts, histological studies of flapped small intestinal muscle cuffs show generally undisturbed healing. Furthermore, monitoring of electrical activities corroborate the viability of the graft. In continent animals, pressure studies show the presence of a high pressure zone in the sphincter canal. The positive pressure profile was maintained and contributes to appropriate closing of the ileostomy. Despite histological, manometrical and electrical criterions of viability of the artificial sphincter, nevertheless the continence achieved by this procedure remains limited because of the restricted ability to contract the small intestinal muscle and the lacking ileal compliance.}, }
@article {pmid6425975, year = {1984}, author = {Hakelius, L and Gierup, J and Grotte, G}, title = {Urinary incontinence in children: treatment with free autogenous muscle transplantation.}, journal = {Progress in pediatric surgery}, volume = {17}, number = {}, pages = {155-167}, pmid = {6425975}, issn = {0079-6654}, mesh = {Adolescent ; Adult ; Animals ; Anus, Imperforate/complications ; Bladder Exstrophy/complications ; Child ; Child, Preschool ; Dogs ; Epispadias/complications ; Fecal Incontinence/etiology/physiopathology/*surgery ; Female ; Follow-Up Studies ; Hirschsprung Disease/complications ; Humans ; Male ; Muscles/*transplantation ; Rats ; *Surgical Flaps ; Urinary Incontinence/etiology/physiopathology/*surgery ; }, abstract = {Free autogenous muscle transplantation has now been carried out in 13 patients with anal incontinence and 16 patients with urinary incontinence. In anal incontinence the results have been excellent; all patients were improved and 12 out of 13 reached an acceptable level of continence. In 10 patients with urinary incontinence the results were good, with increase of functional bladder capacity and abandonment of nappies during the day. Two patients were improved and 4 were failures. Cinematographic studies in both anal and urinary incontinence clearly demonstrated the muscular activity of the transplants and confirmed the existence of a reinnervation process. The longest postoperative observation time is now 7-years in the anal patients and 6 years in the urinary patients.}, }
@article {pmid6425974, year = {1984}, author = {Sauer, H and Höllwarth, M}, title = {Problems of anal continence operations.}, journal = {Progress in pediatric surgery}, volume = {17}, number = {}, pages = {147-153}, pmid = {6425974}, issn = {0079-6654}, mesh = {Adolescent ; Anal Canal/injuries/physiopathology/surgery ; Anus, Imperforate/complications/physiopathology/*surgery ; Child ; Child, Preschool ; Defecation ; Fecal Incontinence/etiology/physiopathology/*surgery ; Hirschsprung Disease/physiopathology/surgery ; Humans ; Male ; Muscles/*transplantation ; *Surgical Flaps ; }, abstract = {After operation for high rectal atresia, incontinence is common. The various operations that are used to cure incontinence can undoubtedly produce considerable improvement. Our own experience and the results published in the literature show that improvement in continence is mainly due to the creation of an elastic barrier that will induce the development of ampullary function in the neorectum. In this connection the mental development of the child is of great importance, as he or she has to become aware of the afferent impulses and act accordingly.}, }
@article {pmid6425973, year = {1984}, author = {Holschneider, AM and Hecker, WC}, title = {Smooth muscle reverse plasty. A new method to treat anorectal incontinence in infants with high anal and rectal atresia. Results after gracilis plasty and free muscle transplantation.}, journal = {Progress in pediatric surgery}, volume = {17}, number = {}, pages = {131-145}, pmid = {6425973}, issn = {0079-6654}, mesh = {Adolescent ; Adult ; Anus, Imperforate/complications/physiopathology/*surgery ; Bladder Exstrophy/complications ; Child ; Defecation ; Fecal Incontinence/etiology/physiopathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Muscle, Smooth/*transplantation ; Muscles/transplantation ; *Surgical Flaps ; }, abstract = {Forty-one patients with Pickrell's gracilis transposition, 6 patients with free muscle transplantations using the Hakelius/Grotte's method, and 2 children with a smooth muscle transplantation after the method described by Schmidt are reported. The results are compared with those reported in the literature. A new operative method is described that can be carried out during infancy at the same time as the abdominal perineal pull-through operation. It involves the fashioning of a smooth muscle cuff formed from a segment of pulled-through colon that is denuded from its mucosa. This cuff is folded back over the distal end of the pulled-through colon. The radiological and manometric results in 2 infants operated upon by this method are described.}, }
@article {pmid6425972, year = {1984}, author = {Holle, J and Freilinger, G}, title = {Improvement of continence by myoplasty of the pelvic floor.}, journal = {Progress in pediatric surgery}, volume = {17}, number = {}, pages = {123-130}, pmid = {6425972}, issn = {0079-6654}, mesh = {Adolescent ; Adult ; Anal Canal/injuries/*surgery ; Animals ; Anus, Imperforate/complications/*surgery ; Child ; Fecal Incontinence/etiology/*surgery ; Follow-Up Studies ; Humans ; Muscles/*transplantation ; *Surgical Flaps ; Swine ; }, abstract = {The authors report their experiences with sphincter reconstructions by free muscle transplant using a denervated muscle with its blood supply intact. The transplanted muscle is fixed to the remaining functioning sphincter musculature. New muscle fibres grow from this muscle into the transplanted muscle, allowing the reconstructed sphincter to contract voluntarily as well as reflexively. The operative technique depends on the existing sphincter defect. Free muscle transplantation is preferred if the external sphincter is still partially existing. Eight patients were examined 2 years after the reconstruction operation and the result was very satisfactory. Solid and semi-solid stool could be controlled by all patients. Large muscle transplantations carried out after the method reported by Thompson (1971) are followed by an increased intramuscular scar formation, as was shown by our experiments. A denervated muscle transposition with its own blood supply is therefore preferable. The change of innervation allows the transplanted muscle to perform its new function. In the treatment of congenital sphincter malformations, a larger muscle, i.e. transposition of the denervated gracilis muscle, should be used. This operation was performed in 7 cases of incontinence following operations for rectal atresia and in 1 case of extensive posttraumatic destruction of the sphincter apparatus. In only 1 case was continence for solid stool achieved. In 6 patients there was a temporary control of fluid stools, but under stress all patients with complex sphincter malformations soiled.}, }
@article {pmid6425971, year = {1984}, author = {Brandesky, G and Geley, L and Janout, D}, title = {Results of the modified Hartl gracilis plasty.}, journal = {Progress in pediatric surgery}, volume = {17}, number = {}, pages = {115-122}, pmid = {6425971}, issn = {0079-6654}, mesh = {Adolescent ; Adult ; Anus, Imperforate/complications/surgery ; Child ; Child, Preschool ; Electromyography ; Electrophysiology ; Fecal Incontinence/diagnosis/etiology/*surgery ; Follow-Up Studies ; Humans ; Male ; Manometry ; Meningomyelocele/complications/surgery ; Wound Healing ; }, abstract = {Follow-up results of patients who had a gracilis plasty for incontinence after rectal atresia showed that in 8 of 11 patients there was marked improvement. 6 children had good continence and 3 sufficient continence. Similar results have been reported by others and are encouraging. The high percentage of infected wounds did not seem to influence the results. The results in operations for incontinence with myelomeningoceles were different. Only 5 times was there sufficient continence and in only 2 patients was subjective improvement recorded. It must be pointed out that the function of the gracilis muscle was tested preoperatively by electromyographic examination. These unsatisfactory results can undoubtedly also be achieved with conservative therapy. Incontinence with myelomeningoceles is therefore no indication for a gracilis plasty. These varying results appear to indicate that success can only be obtained with a gracilis plasty if there are still functioning parts of the pelvic musculature present and if parts of the anorectum are able to mature. If this is true, then there is a direct connection between the results we obtained and those achieved by free muscle transplantation or transposition of a denervated muscle. No doubt, the gracilis plasty is not the only available method to achieve continence, but it will often improve the function of the sphincter in patients with incontinence following rectal atresia operations.}, }
@article {pmid6364328, year = {1984}, author = {Heimdahl, A and Gahrton, G and Groth, CG and Lundgren, G and Lönnquist, B and Ringden, O and Nord, CE}, title = {Selective decontamination of alimentary tract microbial flora in patients treated with bone marrow transplantation. A microbiological study.}, journal = {Scandinavian journal of infectious diseases}, volume = {16}, number = {1}, pages = {51-60}, doi = {10.3109/00365548409068409}, pmid = {6364328}, issn = {0036-5548}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacteria/*growth &amp; development ; *Bone Marrow Transplantation ; Candida albicans/*growth &amp; development ; Digestive System/*microbiology ; Drug Therapy, Combination ; Feces/microbiology ; Female ; Gram-Negative Aerobic Bacteria/growth &amp; development ; Gram-Negative Anaerobic Bacteria/growth &amp; development ; Humans ; Male ; Mouth/*microbiology ; Staphylococcus/growth &amp; development ; Streptococcus/growth &amp; development ; }, abstract = {14 patients undergoing bone marrow transplantation were studied regarding the oral and faecal microflora. Seven patients were given a multidrug regimen, directed against aerobic gram-negative rods and fungi, for local decontamination of the oral cavity and gastrointestinal tract. Seven other patients served as controls. The decontamination regimen was found to decrease the numbers of fungi in the oral cavity and to protect from new colonization. In the gastrointestinal tract aerobic gram-negative rods were eliminated in all patients and new colonization with acquired microorganisms was not observed even when the indigenous anaerobic flora had been disturbed by parenteral antibiotics. In the control group aerobic gram-negative rods and fungi were isolated from all patients during the observation period.}, }
@article {pmid6208107, year = {1984}, author = {Schultze, W and Ezold, R and Kubl, M and Keller, HP}, title = {[Patient and environmental decontamination of patients under bone marrow transplantation].}, journal = {Folia haematologica (Leipzig, Germany : 1928)}, volume = {111}, number = {2}, pages = {224-227}, pmid = {6208107}, issn = {0323-4347}, mesh = {Antisepsis/*methods ; Asepsis/*methods ; *Bone Marrow Transplantation ; Feces/microbiology ; Housekeeping, Hospital ; Humans ; Nursing Staff, Hospital ; Patient Isolators ; Skin/microbiology ; Staphylococcus epidermidis/isolation &amp; purification ; Streptococcus/isolation &amp; purification ; }, }
@article {pmid6628930, year = {1983}, author = {Saverymuttu, SH and Peters, AM and Lavender, JP and Pepys, MB and Hodgson, HJ and Chadwick, VS}, title = {Quantitative fecal indium 111-labeled leukocyte excretion in the assessment of disease in Crohn's disease.}, journal = {Gastroenterology}, volume = {85}, number = {6}, pages = {1333-1339}, pmid = {6628930}, issn = {0016-5085}, mesh = {Blood Sedimentation ; C-Reactive Protein/analysis ; Crohn Disease/*physiopathology ; Feces/*cytology ; Granulocytes/transplantation ; Humans ; *Indium ; Kinetics ; *Leukocytes ; Protein-Losing Enteropathies/diagnosis ; *Radioisotopes ; }, abstract = {The assessment of disease activity in Crohn's disease involves determination of either clinical indexes (e.g., Crohn's disease activity index) or laboratory measurements (e.g., C-reactive protein and erythrocyte sedimentation rate). These have the disadvantage of being indirect and nonspecific correlates of gut inflammation. We have assessed disease activity in Crohn's disease by measurement of fecal leukocyte excretion after intravenous administration of either 111In-labeled mixed leukocyte or pure granulocyte preparations. With mixed leukocyte preparations, fecal excretion of radioactivity correlated with Crohn's disease activity index (r = 0.78, p less than 0.001) and C-reactive protein (r = 0.74, p less than 0.01). Using pure granulocytes, fecal 111In excretion (range 1.5%-52%) was much higher than with mixed leukocytes (range 0.1%-11.0%), showing significant correlations with Crohn's disease activity index (r = 0.731, p less than 0.001), C-reactive protein (r = 0.716, p less than 0.001), and erythrocyte sedimentation rate (r = 0.676, p less than 0.001). Quantitative fecal excretion of 111In-leukocytes is a new method of assessing disease activity in Crohn's disease, specific for bowel inflammation and suitable for objective assessment of disease activity in therapeutic trials.}, }
@article {pmid6650739, year = {1983}, author = {Bushara, HO and Gameel, AA and Majid, BY and Khitma, I and Haroun, EM and Karib, EA and Hussein, MF and Taylor, MG}, title = {Observations on cattle schistosomiasis in the Sudan, a study in comparative medicine. VI. Demonstration of resistance to Schistosoma bovis challenge after a single exposure to normal cercariae or to transplanted adult worms.}, journal = {The American journal of tropical medicine and hygiene}, volume = {32}, number = {6}, pages = {1375-1380}, pmid = {6650739}, issn = {0002-9637}, mesh = {Animals ; Cattle ; Cattle Diseases/*immunology/parasitology ; Feces/parasitology ; Female ; Immunity, Active ; Male ; Parasite Egg Count ; Schistosoma/*immunology/physiology ; Schistosomiasis/parasitology/*veterinary ; Sudan ; }, abstract = {Calves were immunized with Schistosoma bovis by a single experimental exposure to 10,000 normal cercariae. Some of these calves were perfused 14 weeks later, and a part of their worm loads was surgically transplanted into groups of normal recipient calves: "WPR" group calves received 500 pairs of worms; "MR" group calves received between 650 and 1,000 male worms alone. All three groups were subsequently challenged 10 weeks after surgery with 20,000 cercariae, as were a previously unexposed group of controls ("CC"). Mean post-challenge fecal egg counts in the animals immunized with cercariae ("PC" group) rose to a maximum of only 60 eggs per gram (e.p.g.), compared to 376 e.p.g. in the CC, and maximum fecal egg counts in the WPR and MR groups were also somewhat lower than in the CC, at 152 and 250 e.p.g., respectively. In spite of the much lower fecal egg counts in the PC than in the CC group, calculated adult "challenge" worm recoveries were only reduced by 11%, but PC group tissue egg densities derived from the challenge were 78-100% lower than in the CC. The WPR and MR groups had 43% and 37%, respectively, fewer worms than the CC, and mean tissue egg densities were lower by 39-63% and 63-76%, respectively, though in most cases there were no statistically significant differences from the CC.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid6352387, year = {1983}, author = {Weisdorf, SA and Salati, LM and Longsdorf, JA and Ramsay, NK and Sharp, HL}, title = {Graft-versus-host disease of the intestine: a protein losing enteropathy characterized by fecal alpha 1-antitrypsin.}, journal = {Gastroenterology}, volume = {85}, number = {5}, pages = {1076-1081}, pmid = {6352387}, issn = {0016-5085}, support = {2T32-AMO7177/AM/NIADDK NIH HHS/United States ; P01-CA21737/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Anemia, Aplastic/therapy ; *Bone Marrow Transplantation ; Child ; Child, Preschool ; Feces/*analysis ; Graft vs Host Disease/etiology/*metabolism ; Humans ; Intestinal Mucosa/metabolism ; Leukemia/therapy ; Protein-Losing Enteropathies/etiology/*metabolism ; alpha 1-Antitrypsin/*metabolism ; }, abstract = {Severe hypoproteinemia often accompanies the development of graft-versus-host disease of the intestine in allogeneic bone marrow transplant patients. To determine whether or not protein loss occurs across the intestinal mucosa in this severe diarrheal illness, we measured fecal alpha 1-antitrypsin once per week in 24-h stool specimens from 25 consecutive patients during hospitalization for bone marrow transplantation. The mean alpha 1-antitrypsin concentration and serum clearance for these patients before transplantation were below 2.6 mg/g stool and 13.0 ml/day (upper limits for normals). Values for all patients increased moderately after pretransplant conditioning. Values for patients who did not develop graft-versus-host disease of the intestine returned to baseline levels; however, those for patients with graft-versus-host disease of the intestine became markedly and persistently elevated (concentration ranged from 16.6 to 51.1 mg/g, clearance from 66.6 to 384.5 ml/day). We conclude that mucosal protein exudation contributes to the hypoproteinemia of graft-versus-host disease of the intestine and that measurement of fecal alpha 1-antitrypsin can be used as a marker for this disease.}, }
@article {pmid6625062, year = {1983}, author = {Bushara, HO and Hussein, MF and Majid, MA and Musa, BE and Taylor, MG}, title = {Observations on cattle schistosomiasis in the Sudan, a study in comparative medicine. IV. Preliminary observations on the mechanism of naturally acquired resistance.}, journal = {The American journal of tropical medicine and hygiene}, volume = {32}, number = {5}, pages = {1065-1070}, doi = {10.4269/ajtmh.1983.32.1065}, pmid = {6625062}, issn = {0002-9637}, mesh = {Animals ; Cattle ; Cattle Diseases/*immunology ; Feces/parasitology ; Female ; Fertility ; Immune Sera/pharmacology ; Immunity, Innate ; Male ; Parasite Egg Count ; Schistosoma/physiology ; Schistosomiasis/immunology/parasitology/*veterinary ; Sudan ; }, abstract = {Suppression of egg production is the main parasitological manifestation of naturally acquired resistance to Schistosoma bovis in Sudanese cattle. In preliminary investigations on the mechanisms involved, 700-4,000 "suppressed" adult worms were surgically transplanted from six "resistant" donor cattle with very low fecal egg counts (0-8 eggs/g, epg) into six normal recipients. After transplantation, large numbers of eggs were excreted in the feces of the recipient cattle, beginning at between 5 and 16 days after operation, and reaching counts of 55-405 epg at between 6 and 20 days post transplantation. In the cattle with the highest egg counts, egg counts soon fell sharply from peak levels, whereas in cattle with lower peak counts, more steady counts were maintained. All the recipients were perfused at days 46-56, when between 0.1% and 78.5% of the transplanted worms were recovered. In the second experiment, 1,000-ml quantities of pooled sera from "resistant" donors were injected intraperitoneally into each of four normal recipient calves, while another four were injected with pooled sera from uninfected cattle. All the calves were challenged percutaneously the next day with 7,500 cercariae each, and the course of infection was followed by parasitological and clinical measurements until perfusion 18 weeks later. The results showed that the "immune" sera had a negligible effect on the numbers of worms which developed, and had no significant effect on the fecal egg counts or clinical parameters studied. There was, however, some evidence from the tissue egg counts of a reduction in the fecundity of the worms in calves injected with "immune" sera.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid6680848, year = {1983}, author = {Signorelli, I and Andreoni, GM and Capelli, G and Gozzini, PA}, title = {[Anal incontinence].}, journal = {Chirurgia italiana}, volume = {35}, number = {3}, pages = {358-391}, pmid = {6680848}, issn = {0009-4773}, mesh = {Aged ; Anal Canal/physiopathology/*surgery ; Fecal Incontinence/etiology/*therapy ; Female ; Gastrointestinal Motility ; Humans ; Muscles/transplantation ; Sutures ; }, abstract = {The Authors describe the clinical rectal incontinence according to etiology, physiology and pathologic anatomy. They report a case of such rectal incontinence followed to hemorroidectom and treated by transplantation of gracilis muscle according to Pikrell technique, comparing this approach with other current surgical procedures.}, }
@article {pmid6414860, year = {1983}, author = {Schmidt, RE and Plurad, SB and Olack, BJ and Scharp, DW}, title = {The effect of pancreatic islet transplantation and insulin therapy on experimental diabetic autonomic neuropathy.}, journal = {Diabetes}, volume = {32}, number = {6}, pages = {532-540}, doi = {10.2337/diab.32.6.532}, pmid = {6414860}, issn = {0012-1797}, support = {AM 00318/AM/NIADDK NIH HHS/United States ; AM 19645/AM/NIADDK NIH HHS/United States ; AM 26083/AM/NIADDK NIH HHS/United States ; }, mesh = {Animals ; Axons/pathology/ultrastructure ; Blood Glucose ; Diabetes Mellitus, Experimental/*therapy ; Diabetic Neuropathies/pathology/*therapy ; Insulin/*therapeutic use ; Intestine, Small/innervation ; *Islets of Langerhans Transplantation ; Male ; Mesentery/innervation ; Rats ; Rats, Inbred WF ; }, abstract = {Rats with chronic streptozotocin (SZ) diabetes develop dilatation of the alimentary tract, loss of fecal consistency, and autonomic neuropathy involving unmyelinated axons of the extrinsic innervation of the small bowel. Diabetic autonomic neuropathy involving the ileal mesenteric nerves is characterized by modest to marked dilatation of axons by distinctive subcellular organelles identical to those described in experimental and clinical axonal dystrophies. Axonopathy is confined to the alimentary tract; examination of myelinated and unmyelinated axons of the sciatic (midthigh level) and distal somatic nerves of the tail of diabetic animals with prominent ileal axonopathy failed to demonstrate significant numbers of dystrophic axons. The prevention or reversal of diabetic autonomic neuropathy by a variety of experimental manipulations clearly indicates that the lesions we have demonstrated in chronically SZ-induced diabetic animals were produced by diabetes and were not the result of a direct neurotoxic effect of the diabetogenic agent streptozotocin. Animals did not develop axonopathy after simultaneous administration of SZ and nicotinamide, a procedure which prevents pancreatic beta-cell necrosis and induction of diabetes while exposing the nervous system to a possible neurotoxic agent. Selected animals that were given SZ, became diabetic, and subsequently received daily insulin therapy or pancreatic islet transplantation also did not develop axonopathy. Transplantation of pancreatic islets 6 mo after induction of diabetes, a time at which mesenteric axonopathy was well developed, quickly reestablished normoglycemia, and within 3 mo resulted in nearly complete resolution of the neuropathy. Mild chronic diabetes maintained for 5-6 mo failed to produce significant levels of axonopathy.(ABSTRACT TRUNCATED AT 250 WORDS)}, }
@article {pmid6880529, year = {1983}, author = {Holschneider, AM}, title = {Treatment and functional results of anorectal continence in children with imperforate anus.}, journal = {Acta chirurgica Belgica}, volume = {82}, number = {3}, pages = {191-204}, pmid = {6880529}, issn = {0001-5458}, mesh = {Anus, Imperforate/mortality/*surgery ; Fecal Incontinence/diagnosis/etiology ; Female ; Humans ; Infant, Newborn ; Male ; Manometry ; Methods ; Muscle, Smooth/transplantation ; Muscles/transplantation ; Postoperative Complications ; }, abstract = {The results of 172 patients with imperforate anus are reported. In these patients 215 operations where performed. The complications, lethality and the results concerning anorectal continence are analysed. The lethality was 58% in the risk group A (high risk), 27% in group B and 3% in C group (low risk). The overall lethality was 16.6%. Specific complications were anal stenosis (15.5%), relapse of anorectal or anovaginal fistulas (7%) and mucosa prolapse (5%). Anorectal continence was evaluated according to the Kelly score of continence and to our own electromanometric and clinical score. Five years after the operation 50% of the patients with high type, and 14% of those with low type imperforate anus remained incontinent. Only 15% of the high anal atresias and 43% of the low forms became continent. Thirty-five percent of the children with a high anorectal malformation and 43% with a low type acquired a partial continence with small amounts of soiling. The current surgical techniques to improve anorectal continence are discussed: Pickrell's gracilis transplantation and its modifications, the free muscle transplantation according to Hakelius and Grotte, the free smooth muscle transplantation according to Schmidt and the reverse smooth muscle transplantation according to Holschneider and Hecker. Clinical and electromanometrical as well as electromyographical results are presented.}, }
@article {pmid6637112, year = {1983}, author = {Engels, M and Patzner, R}, title = {[Clinical, manometric and electron microscope follow-up studies of the transposed gracilis muscle in anorectal incontinence].}, journal = {Zeitschrift fur Kinderchirurgie : organ der Deutschen, der Schweizerischen und der Osterreichischen Gesellschaft fur Kinderchirurgie = Surgery in infancy and childhood}, volume = {38}, number = {2}, pages = {95-100}, doi = {10.1055/s-2008-1059946}, pmid = {6637112}, issn = {0174-3082}, mesh = {Anal Canal/*surgery ; Child ; Fecal Incontinence/*surgery ; Follow-Up Studies ; Humans ; Manometry ; Microscopy, Electron ; Muscle Contraction ; Muscles/*transplantation/ultrastructure ; }, abstract = {The article reports on six children with complete incontinence. Two patients had lumbar myelomeningocele, whereas four had a supralevatory anorectal atresia. They were given a modified sphincter substitute graft by means of the m. gracilis. Proof of full functional ability of the "neosphincter" is supplied via manometrical and electron microscope studies.}, }
@article {pmid6855107, year = {1983}, author = {Dul'tsev, IuV}, title = {[Treatment of incompetence of the anal sphincter].}, journal = {Khirurgiia}, volume = {}, number = {3}, pages = {82-87}, pmid = {6855107}, issn = {0023-1207}, mesh = {Adolescent ; Adult ; Anal Canal/physiopathology/*surgery ; Buttocks ; Fecal Incontinence/*surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscles/transplantation ; Thigh ; }, }
@article {pmid6855105, year = {1983}, author = {Rykov, VI}, title = {[Surgical rehabilitation of patients with the loss of the anal sphincter].}, journal = {Khirurgiia}, volume = {}, number = {3}, pages = {79-82}, pmid = {6855105}, issn = {0023-1207}, mesh = {Adolescent ; Adult ; Anal Canal/*surgery ; Colostomy/methods ; Fascia/transplantation ; Fecal Incontinence/*rehabilitation ; Female ; Humans ; Magnetics ; Male ; Middle Aged ; Muscles/transplantation ; Postoperative Complications/prevention &amp; control ; Prostheses and Implants ; }, }
@article {pmid6298949, year = {1983}, author = {Bolivar, R}, title = {Rotavirus screening in adult cancer patients.}, journal = {Southern medical journal}, volume = {76}, number = {3}, pages = {418}, doi = {10.1097/00007611-198303000-00044}, pmid = {6298949}, issn = {0038-4348}, mesh = {Adolescent ; Adult ; Aged ; Bone Marrow/microbiology ; Bone Marrow Transplantation ; Feces/microbiology ; Graft vs Host Reaction ; Humans ; Leukemia/microbiology ; Middle Aged ; Neoplasms/*microbiology ; Rotavirus/*isolation &amp; purification ; }, }
@article {pmid6868035, year = {1983}, author = {Kvarstein, B and Mathisen, W}, title = {[Fecal incontinence treated by transplantation of the gracilis muscle. A follow-up study].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {103}, number = {6}, pages = {599-600}, pmid = {6868035}, issn = {0029-2001}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/surgery ; Fecal Incontinence/*therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscles/*transplantation ; }, }
@article {pmid6350024, year = {1983}, author = {Smith, DE and Benet, LZ}, title = {Biotransformation of furosemide in kidney transplant patients.}, journal = {European journal of clinical pharmacology}, volume = {24}, number = {6}, pages = {787-790}, pmid = {6350024}, issn = {0031-6970}, support = {AM 20884/AM/NIADDK NIH HHS/United States ; GM 07175/GM/NIGMS NIH HHS/United States ; }, mesh = {Biotransformation ; Chromatography, High Pressure Liquid ; Furosemide/*metabolism ; Glucuronates/urine ; Humans ; *Kidney Transplantation ; }, abstract = {The metabolic fate of furosemide was studied in kidney transplant patients after oral and intravenous administration of the diuretic at therapeutic doses. Serial urine samples were collected over a 24 h period and furosemide was analyzed by a specific high performance liquid chromatographic method using fluorescence detection. We found no evidence of the putative furosemide metabolite, 2-amino-4-chloro-5-sulfamoylanthranilic acid (CSA), in any of the samples analyzed. The amount of furosemide excreted as the glucuronide metabolite accounted for 8% of the available dose, whether administered orally or by intravenous infusion. In addition, the significant positive correlation observed between the percent of the available dose excreted as furosemide glucuronide and the renal clearance of furosemide (r = 0.581, p less than 0.02) suggests that the glucuronidation process for furosemide may be occurring in the kidney. Furosemide and its glucuronide metabolite accounted for only 45% of the intravenous dose recovered in the urine. Biliary excretion of unchanged furosemide and/or furosemide glucuronide into the feces probably accounts for the remainder of the dose not recovered.}, }
@article {pmid6339774, year = {1983}, author = {Funada, H and Teshima, H and Hattori, K}, title = {Total intestinal decontamination for prevention of infection in bone marrow transplantation.}, journal = {Japanese journal of clinical oncology}, volume = {13 Suppl 1}, number = {}, pages = {111-126}, pmid = {6339774}, issn = {0368-2811}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Bacteria/drug effects ; Bacterial Infections/*prevention &amp; control ; *Bone Marrow Transplantation ; Drug Resistance, Microbial ; Feces/microbiology ; Female ; Fungi/drug effects ; Humans ; Intestinal Absorption ; Intestines/*microbiology ; Male ; Middle Aged ; Mycoses/*prevention &amp; control ; Neoplasms/therapy ; Pharynx/microbiology ; }, abstract = {In an attempt to prevent infections complicating bone marrow transplantation, 22 patients received oral nonabsorbable antibiotics in protected environments. The standard antibiotic regimen consisted of gentamicin, vancomycin and nystatin. The vast majority of fecal organisms initially cultured were completely suppressed by about one week after initiation of antibiotic prophylaxis. The antibiotics had to be taken regularly to keep the gastrointestinal tract decontaminated. However, Candida was often cultured despite prophylaxis. The best method for continuously suppressing Candida was considered to be administering an adequate antifungal drug before intestinal decontamination. The throat, however, was far more difficult to decontaminate than the stool. Lincomycin inhalation was most effective in suppressing anaerobic bacteria. Some of the organisms cultured persistently or intermittently from the throat tended to appear sooner or later in the stool during prophylaxis, although they were not always resistant. The pattern of reappearance of the fecal flora after intestinal decontamination was similar to that observed in newborn infants. However, none of the Enterobacteriaceae strains which reappeared in the stool were identical to those cultured initially. Absorption of gentamicin and vancomycin from the gastrointestinal tract was negligible. A gentamicin-induced small-colony variant of Klebsiella pneumoniae was isolated from one patient. Amphotericin B was more tolerable than nystatin, which often produced nausea and vomiting in association with the preparative radio-chemotherapy for marrow transplantation. Hypoprothrombinemia and hypocholesterolemia were noted during prophylaxis. Three episodes of exogenous bacterial infection occurred despite strict isolation procedures.}, }
@article {pmid7168924, year = {1982}, author = {Goldsmith, HS and Steward, E}, title = {Fecal continence after abdominoperineal resection using the pedicled pyloric valve--an experimental study.}, journal = {Clinical oncology}, volume = {8}, number = {4}, pages = {313-317}, pmid = {7168924}, issn = {0305-7399}, mesh = {Animals ; Cats ; Colon/*surgery ; Fecal Incontinence/*surgery ; Perineum/*surgery ; Pylorus/blood supply/*transplantation ; }, }
@article {pmid7121880, year = {1982}, author = {Georgacopulo, P}, title = {[Muscle transplantation as a means of achieving continence in ano-rectal atresia].}, journal = {Minerva medica}, volume = {73}, number = {39}, pages = {2667-2670}, pmid = {7121880}, issn = {0026-4806}, mesh = {Anus, Imperforate/complications ; Fecal Incontinence/etiology/*therapy ; Humans ; Infant ; Infant, Newborn ; Intestinal Atresia/*complications ; Methods ; Muscle, Smooth/transplantation ; Muscles/*transplantation ; Rectum/abnormalities ; }, abstract = {Correction of incontinence as the sequel of a pull-through operation for anorectal atresia, leaving aside cases due to a mistake of the surgical technique, is based on the construction of a new sphincter. This can be done in several ways, using striped, pedicled, denervated, free, or, more recently, smooth muscle. The techniques, objectives, and results are described with reference to the latest data in the literature.}, }
@article {pmid7151503, year = {1982}, author = {Häring, R and Berlien, P and Karavias, T}, title = {[Reconstruction of the natural anus using diagonally striated muscles].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {53}, number = {10}, pages = {605-610}, pmid = {7151503}, issn = {0009-4722}, mesh = {Adolescent ; Adult ; Anal Canal/*surgery ; Fecal Incontinence/surgery ; Female ; Humans ; Male ; Methods ; Middle Aged ; Muscles/*transplantation ; }, }
@article {pmid7151502, year = {1982}, author = {Beger, HG and Schmidt, E and Pistor, G}, title = {[Reconstruction of the natural anus by transplantation of smooth intestinal muscles].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {53}, number = {10}, pages = {599-604}, pmid = {7151502}, issn = {0009-4722}, mesh = {Adult ; Anal Canal/*surgery ; Animals ; Child ; Colon ; Fecal Incontinence/surgery ; Humans ; Methods ; Muscle, Smooth/*transplantation ; }, }
@article {pmid7148143, year = {1982}, author = {Holschneider, AM}, title = {[Timing of myokinetic sphincter replacement surgery in fecal and urinary incontinence].}, journal = {Zeitschrift fur Kinderchirurgie : organ der Deutschen, der Schweizerischen und der Osterreichischen Gesellschaft fur Kinderchirurgie = Surgery in infancy and childhood}, volume = {37}, number = {1}, pages = {11-14}, doi = {10.1055/s-2008-1059806}, pmid = {7148143}, issn = {0174-3082}, mesh = {Adolescent ; Adult ; Age Factors ; Child ; Child, Preschool ; Fecal Incontinence/*surgery ; Humans ; Muscle, Smooth/transplantation ; Muscles/transplantation ; Urinary Incontinence/*surgery ; }, abstract = {In 71 children on whom surgery to improve continence was performed mainly because of severe anorectal atresia, an investigation was carried out to find out whether there was a relationship between the patients' age at the time of operation and post-surgical continence. It was found that both after transplantation of the gracilis muscle according to Pickrell and after free muscle transplantation, the results obtained improved the more, the older the children at the time of surgery, and the more active their participation had been in postoperative intensive stool training. However, the authors' hope has so far not materialised that stool training would become redundant by free muscular transplantation, due to the reflectory introduction of freely transplanted musculature into the continence mechanism and the resulting spontaneous innervation and activation of the muscle. This would have facilitated early performance of an operation to improve continence.}, }
@article {pmid7051383, year = {1982}, author = {Pemberton, JH and Heppell, J and Beart, RW and Dozois, RR and Telander, RL}, title = {Endorectal ileoanal anastomosis.}, journal = {Surgery, gynecology &amp; obstetrics}, volume = {155}, number = {3}, pages = {417-424}, pmid = {7051383}, issn = {0039-6087}, mesh = {Adult ; Aged ; Anal Canal/physiology/*surgery ; Colitis, Ulcerative/surgery ; Humans ; Ileostomy ; Ileum/*surgery ; Intestinal Mucosa/surgery ; Intestinal Polyps/genetics/surgery ; Methods ; Rectum/*surgery ; Transplantation, Homologous ; }, abstract = {In 1933, Nissen performed the first ileoanal anastomosis. Since then, ileoanal anastomosis has enjoyed only periodic popularity because numerous postoperative problems, primarily as a result of infection and incontinence, plagued the procedure. In recent reports, however, better postoperative results have been detailed which stem not only from improved surgical technique and better selection of patients but also from increased understanding of the physiologic mechanisms by which fecal continence is achieved. At operation, meticulous hemostasis and asepsis, accurate en bloc mucosal dissection and effective drainage each contribute to good functional results and the minimization of complications. In addition, patients who manifest evidence of dysfunction of anal sphincters, who are elderly or obese or who have Crohn's disease should not be candidates for ileoanal anastomosis. Finally, if the anal sphincters are intact, reliable ileal reservoir function, achieved by passive dilation, balloon distention or surgical construction of a pouch, may be the most important determinate of excellent clinical results after ileoanal anastomosis.}, }
@article {pmid6756814, year = {1982}, author = {Schmidt, E and Bruch, HP}, title = {[The continent colostomy].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {53}, number = {9}, pages = {551-555}, pmid = {6756814}, issn = {0009-4722}, mesh = {Adolescent ; Adult ; Aged ; Child ; Colostomy/*methods ; Electromyography ; Fecal Incontinence/*prevention &amp; control ; Female ; Humans ; Male ; Manometry ; Middle Aged ; Muscle, Smooth/transplantation ; Postoperative Care ; Postoperative Complications/prevention &amp; control ; Suture Techniques ; }, }
@article {pmid7136298, year = {1982}, author = {Paus, A and Bjordal, R and Refsum, S and Knutrud, O}, title = {Anorectal anomalies--international classification.}, journal = {Zeitschrift fur Kinderchirurgie : organ der Deutschen, der Schweizerischen und der Osterreichischen Gesellschaft fur Kinderchirurgie = Surgery in infancy and childhood}, volume = {36}, number = {2}, pages = {58-62}, doi = {10.1055/s-2008-1059862}, pmid = {7136298}, issn = {0174-3082}, mesh = {Abnormalities, Multiple ; Anal Canal/*abnormalities ; Congenital Abnormalities/*classification ; Fecal Incontinence/surgery ; Female ; Humans ; Male ; Muscles/transplantation ; Rectum/*abnormalities ; }, abstract = {80 patients with anorectal anomalies were admitted to the Paediatric Surgical Service of the National Hospital of Norway during the five year period 1970--74. The anomalies were classified according to the International Classification which was found to be of obvious value in comparing material and results. Intermediate and high deformities were generally treated with an initial colostomy and a subsequent sacroperineal pullthrough operation. The low anomalies were generally treated with an anoplasty in two procedures. Patients with poor functional results and incontinence can be improved with free muscle transplantation.}, }
@article {pmid7038501, year = {1982}, author = {Yolken, RH and Bishop, CA and Townsend, TR and Bolyard, EA and Bartlett, J and Santos, GW and Saral, R}, title = {Infectious gastroenteritis in bone-marrow-transplant recipients.}, journal = {The New England journal of medicine}, volume = {306}, number = {17}, pages = {1009-1002}, doi = {10.1056/NEJM198204293061701}, pmid = {7038501}, issn = {0028-4793}, support = {CA 06973/CA/NCI NIH HHS/United States ; CA 15396-08/CA/NCI NIH HHS/United States ; N01 AI92616/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Anemia, Aplastic/therapy ; *Bone Marrow Transplantation ; Clostridium Infections/etiology ; Feces/microbiology ; Female ; Gastroenteritis/*etiology/microbiology ; Graft vs Host Reaction ; Humans ; Infections/*etiology ; Leukemia/therapy ; Male ; Postoperative Complications ; Prospective Studies ; Sepsis/etiology ; Virus Diseases/etiology ; }, abstract = {We prospectively evaluated infections with several gastrointestinal pathogens in patients undergoing bone-marrow transplantation, in an attempt to correlate infection with morbidity and mortality. Thirty-one of 78 patients (40 per cent) were infected with one or more of the following enteric pathogens during the study: adenovirus (12 infections), rotavirus (nine), coxsackievirus (four), or Clostridium difficile (12). Several patients were infected with more than one pathogen. Infection correlated with the occurrence of diarrhea and abdominal cramps. The mortality rate among the infected patients was 55 per cent--significantly higher than the rate (13 per cent) among the noninfected patients (P less than 0.001). This study indicates that enteric pathogens that often cause mild diarrhea in normal populations can cause serious infections in marrow-transplant recipients. Measures aimed at preventing or treating such infections might reduce the morbidity and mortality associated with marrow transplantation.}, }
@article {pmid6122055, year = {1982}, author = {Townsend, TR and Bolyard, EA and Yolken, RH and Beschorner, WE and Bishop, CA and Burns, WH and Santos, GW and Saral, R}, title = {Outbreak of Coxsackie A1 gastroenteritis: a complication of bone-marrow transplantation.}, journal = {Lancet (London, England)}, volume = {1}, number = {8276}, pages = {820-823}, doi = {10.1016/s0140-6736(82)91872-4}, pmid = {6122055}, issn = {0140-6736}, support = {1-R01A117604-01//PHS HHS/United States ; 266-792616//PHS HHS/United States ; CA06973/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, Viral/isolation &amp; purification ; *Bone Marrow Transplantation ; *Coxsackievirus Infections/immunology ; Disease Outbreaks/*epidemiology ; Enterovirus/isolation &amp; purification ; Feces/microbiology ; Gastroenteritis/epidemiology/*etiology/mortality ; Graft vs Host Reaction ; Humans ; Maryland ; Pharynx/microbiology ; Risk ; }, abstract = {In a three-week period 7 of 14 transplant recipients were infected with coxsackie A1 virus. Diarrhoea and mortality were significantly associated with infection (7 of 7 infected compared with 0 of 7 non-infected, and 6 of 7 infected compared with 1 of 7 non-infected, respectively). Early in the outbreak, the diarrhoea was presumed to be due to acute graft-versus-host disease (AGVHD). However, the distribution of AGVHD among infected and non-infected patients was nearly equal, and at necropsy 3 of 6 infected patients who had had diarrhoea showed no evidence of gastrointestinal involvement with AGVHD. Infection with viral enteric pathogens may be an important factor in the clinical course of transplant recipients.}, }
@article {pmid7077473, year = {1982}, author = {Prochiantz, A and Gross, P}, title = {Gluteal myoplasty for sphincter replacement: principles, results and prospects.}, journal = {Journal of pediatric surgery}, volume = {17}, number = {1}, pages = {25-30}, doi = {10.1016/s0022-3468(82)80320-5}, pmid = {7077473}, issn = {0022-3468}, mesh = {Anal Canal/abnormalities/*surgery ; Buttocks ; Fecal Incontinence/*surgery ; Humans ; Methods ; Muscles/*transplantation ; Rectum/abnormalities/*surgery ; }, abstract = {The treatment of anal incontinence following anorectal malformations and their treatment can be done even if the colic pull-down has been carried out of the levatori ani muscle sling. The use of the gluteus maximus encircling the neorectum with a contractile muscular ring provides an active control of continence, and reverses the anorectal angulation. The rationale of the myoplasty has been pointed out and our first resulted analyzed. The use of voluntary contraction limits the scope of an operation whose effects can be lost during sleep. But the voluntary daytime control makes it possible for the patient to take part in school, occupational or sportive activities.}, }
@article {pmid7040314, year = {1982}, author = {Schmidt, E}, title = {[Continent colostomy].}, journal = {Helvetica chirurgica acta}, volume = {48}, number = {6}, pages = {855-862}, pmid = {7040314}, issn = {0018-0181}, mesh = {Adolescent ; Adult ; Aged ; Child ; Colostomy/*methods ; Fecal Incontinence/*prevention &amp; control ; Humans ; Middle Aged ; Muscle, Smooth/*transplantation ; Postoperative Complications/*prevention &amp; control ; Rectum/transplantation ; Suture Techniques ; }, }
@article {pmid6809852, year = {1982}, author = {Funada, H and Teshima, H and Hattori, K}, title = {[Reconstitution of fecal and pharyngeal flora after total intestinal decontamination (author's transl)].}, journal = {Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases}, volume = {56}, number = {2}, pages = {141-151}, doi = {10.11150/kansenshogakuzasshi1970.56.141}, pmid = {6809852}, issn = {0387-5911}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Bacterial Infections/prevention &amp; control ; Bone Marrow Transplantation ; Feces/*microbiology ; Humans ; Intestines/*microbiology ; Male ; Middle Aged ; Patient Isolators ; Pharynx/*microbiology ; Premedication ; }, }
@article {pmid7049955, year = {1982}, author = {}, title = {E.O.R.T.C. Gnotobiotic Project Group: a prospective cooperative study of antimicrobial decontamination in granulocytopenic patients. Comparison of two different methods.}, journal = {Infection}, volume = {10}, number = {3}, pages = {131-138}, pmid = {7049955}, issn = {0300-8126}, mesh = {Acute Disease ; Adolescent ; Adult ; Agranulocytosis/*drug therapy ; Anti-Bacterial Agents/analysis/*therapeutic use ; Bacterial Infections/*prevention &amp; control ; Bone Marrow Transplantation ; Child ; Child, Preschool ; Drug Combinations ; Drug Evaluation ; Drug Therapy, Combination ; Feces/analysis/microbiology ; Female ; Humans ; Intestines/*microbiology ; Leukemia/complications ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Neutropenia/complications/*drug therapy/microbiology ; Prospective Studies ; Random Allocation ; }, abstract = {In a cooperative and prospectively randomized study, two different methods of antimicrobial decontamination of the digestive tract with oral, nonabsorbable antibiotics were compared in neutropenic patients. In the first treatment group, the antibiotics were selected on the basis of the outcome of sensitivity tests performed on the flora of the patients. The other treatment group was given a standard combination of neomycin, cephaloridin, polymyxin B or E and nystatin or amphotericin B. Complete data from a total of 35 patients were received at the Statistical Center, and a minimum of 1.5 oral washings and faecal samples per week arrived at the Central Bacteriological Laboratory. There was no substantial difference in the clinical parameters of the patients in both treatment groups. Both methods for decontamination were found to be effective. The incidence of acquired infections and the quality of decontamination were almost identical in both groups. As far as the average number of negative cultures per patient is concerned, the results for both treatment groups are well in line with data found in other studies using a combination of gentamicin, vancomycin and nystatin.}, }
@article {pmid7045710, year = {1982}, author = {Day, RS and Eales, L}, title = {Porphyrins in renal transplantation.}, journal = {Nephron}, volume = {30}, number = {1}, pages = {22-27}, doi = {10.1159/000182426}, pmid = {7045710}, issn = {1660-8151}, mesh = {Adult ; Coproporphyrins/analysis ; Creatinine/blood/urine ; Erythrocytes/analysis ; Feces/analysis ; Female ; Humans ; *Kidney Transplantation ; Male ; *Porphyrias ; Porphyrins/*analysis/blood/urine ; Protoporphyrins/analysis ; Uroporphyrins/analysis ; }, abstract = {The porphyrin status of 38 renal transplant patients was investigated using a sensitive thin-layer chromatographic assay. Abnormalities of porphyrin synthesis observed in patients on hemodialysis were generally reversed on receipt of a transplant with sustained good renal function. Urinary coproporphyrin levels and the creatinine clearance appeared directly related in both individual cases and generally, substantiating the theory that coproporphyrin is of renal origin. The pre- and postoperative porphyrin status of a unique patient with variegate porphyria who received a successful renal transplant implies that the excess urinary porphyrins and precursors excreted in the acute porphyrias are also of mainly renal, as opposed to hepatic origin. Furthermore, the posttransplant overproduction of porphyrins by a kidney from a normal donor suggests the existence of an endogenous porphyrogenic agent in the circulation of patients with acute porphyria.}, }
@article {pmid7338775, year = {1981}, author = {Holschneider, AM and Hecker, WC}, title = {Reverse smooth muscle plasty: a new method of treating anorectal incontinence in infants with high anal and rectal atresia.}, journal = {Journal of pediatric surgery}, volume = {16}, number = {6}, pages = {917-920}, doi = {10.1016/s0022-3468(81)80846-9}, pmid = {7338775}, issn = {0022-3468}, mesh = {Anal Canal/*abnormalities/*surgery ; Colon/surgery ; Fecal Incontinence/*surgery ; Humans ; Infant ; Intestinal Atresia/*surgery ; Methods ; Muscle, Smooth/*transplantation ; Rectum/abnormalities ; }, abstract = {A new technique of treating anorectal incontinence in infants with high anal and rectal atresia is described. In the first stage of this new operation an abdominosacroperineal pull-through procedure according to Rehbein, Romualdi, and Kiesewetter is performed. In the next step of this new method the circular and longitudinal muscle layers of the pulled-through colon are turned back 180 degree and fixed to the pulled-through bowel. The mucosa of the turned back bowel is removed. Then the whole muscle cuff is re-pulled into the puborectalis sling. Pressure studies as well as X-ray investigations showed a good sphincter function of the newly established internal sphincter equivalent.}, }
@article {pmid7343945, year = {1981}, author = {Belloli, GP and Campobasso, P and Girardi, GF and Termini, C}, title = {[Free autogenous muscle grafts in nine children with total and incontinence (author's transl)].}, journal = {La Pediatria medica e chirurgica : Medical and surgical pediatrics}, volume = {3}, number = {6}, pages = {481-485}, pmid = {7343945}, issn = {0391-5387}, mesh = {Adolescent ; Anus Diseases/complications/*surgery ; Child ; Fecal Incontinence/etiology/*surgery ; Humans ; Male ; Muscles/*transplantation ; }, abstract = {Nine children with total anal incontinence after surgery for anorectal agenesis were successfully operated on by free autogenous muscle transplantation. Skeletal muscles were first denervated and 3 weeks later transplanted to the anal region as a U--sling around the rectum, imitating the normal position and function of the puborectalis muscle. The grafts were placed in contact with the normal muscles of the region to make reinnervation possible. Eight children were completely evaluated after operation. Two years after surgical procedure six children were "continent" and only two were still incontinent, but improved. In these cases the indication for muscle transplantation was not quite correct. The return of the function of the muscle grafts completely changed the lives of these children. The results of this new surgical procedure are encouraging and invite further trials.}, }
@article {pmid7337909, year = {1981}, author = {Fayer, R}, title = {Toxoplasmosis update and public health implications.}, journal = {The Canadian veterinary journal = La revue veterinaire canadienne}, volume = {22}, number = {11}, pages = {344-352}, pmid = {7337909}, issn = {0008-5286}, mesh = {Animals ; Cat Diseases/*parasitology/transmission ; Cats ; Cattle ; Humans ; Immunosuppression Therapy ; Public Health ; Toxoplasma ; Toxoplasmosis/immunology/*parasitology ; Toxoplasmosis, Animal/epidemiology/*transmission ; }, abstract = {Toxoplasma gondii has a coccidian life cycle in the intestine of domestic and wild felids that includes a series of asexual and sexual stages and an oocyst stage that is shed in the feces. Oocysts complete their development outside the body, eventually becoming infective for about 350 species of vertebrates including cats and man. The effects of climate on oocyst survival and the physical and biological means of oocyst dispersal are discussed. Infectivity and pathogenicity for livestock species vary. Acute disease results from rapidly multiplying tachyzoites that may be transmitted by carnivorism, transfusion, vertical transmission and other routes. Patent infections may persist for the life of a host as bradyzoites within tissue cysts. Bradyzoites initiate acute infection in other hosts after carnivorism or organ transplantation or in the same host after immunosuppression. Also discussed are: (a) prevalence of T. gondii in livestock as determined by digestion and serological techniques, (b) identification in humans as accomplished by isolation, serological and skin test techniques and (c) identification in cats as accomplished primarily by fecal examinations for oocysts infective for mice. Source of human infections, major outbreaks, treatment, effects on mental health and methods for preventing toxoplasmosis in man and livestock are listed.}, }
@article {pmid7297363, year = {1981}, author = {Kalisman, M and Sharzer, LA}, title = {Anal sphincter reconstruction and perineal resurfacing with a gracilis myocutaneous flap.}, journal = {Diseases of the colon and rectum}, volume = {24}, number = {7}, pages = {529-531}, doi = {10.1007/BF02604315}, pmid = {7297363}, issn = {0012-3706}, mesh = {Aged ; Anal Canal/*surgery ; Fecal Incontinence/prevention &amp; control ; Female ; Follow-Up Studies ; Humans ; Muscles/*transplantation ; Perineum/*surgery ; Proctitis/surgery ; Radiation Injuries/surgery ; Radiodermatitis/surgery ; *Surgical Flaps ; Thigh ; }, }
@article {pmid7314668, year = {1981}, author = {Meissner, F}, title = {[The free autogenous muscle transplantation in anal incontinence].}, journal = {Zeitschrift fur arztliche Fortbildung}, volume = {75}, number = {13}, pages = {564-566}, pmid = {7314668}, issn = {0044-2178}, mesh = {Adolescent ; Child ; Denervation ; Fecal Incontinence/etiology/*therapy ; Female ; Humans ; Intestinal Atresia/complications/*surgery ; Muscles/*transplantation ; }, }
@article {pmid7251056, year = {1981}, author = {Dawkins, HJ and Grove, DI}, title = {Transfer by serum and cells of resistance to infection with Strongyloides ratti in mice.}, journal = {Immunology}, volume = {43}, number = {2}, pages = {317-322}, pmid = {7251056}, issn = {0019-2805}, mesh = {Animals ; Dose-Response Relationship, Immunologic ; Feces/parasitology ; Female ; Immune Sera/*immunology ; *Immunization, Passive ; Lymph Nodes/immunology ; Lymphocyte Transfusion ; Lymphocytes/*immunology ; Mesentery ; Mice ; Mice, Inbred C57BL ; Spleen/immunology ; Strongyloidiasis/*immunology ; Transplantation, Isogeneic ; }, abstract = {C57Bl/6 mice were infected with Strongyloides ratti. Susceptibility to infection was ascertained by quantifying the numbers of larvae in the faeces 1 week after infection. Resistance to infection was transferred by pooled immune serum and mesenteric lymph node (MLN) cells obtained 2 and 3 weeks after infection. There was no additive effect when immune serum and MLN cells were given together. Protection was not conferred by MLN cells 1, 4 or 6 weeks after infection nor by spleen cells taken 1--6 weeks after infection. There was, however, a mild non-specific reduction in larval excretion after transfer of either normal or immune spleen cells. These data indicate that both humoral and cell-mediated immune responses may confer resistance to infection in murine strongyloidiasis.}, }
@article {pmid7251696, year = {1981}, author = {Schmidt, E and Bruch, HP}, title = {[Autotransplantation of smooth muscle for treating incontinence of sphincters (author's transl)].}, journal = {Journal de chirurgie}, volume = {118}, number = {5}, pages = {315-320}, pmid = {7251696}, issn = {0021-7697}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/*surgery ; Animals ; Child ; Dogs ; Fecal Incontinence/*surgery ; Humans ; Middle Aged ; Muscle, Smooth/*transplantation ; Transplantation, Autologous ; }, abstract = {By histologic, electronoptic, perfusion manometric and microangiographic examination it was demonstrated, that the smooth muscle of the intestinal tract can be autotransplanted and can function as a sphincter after healing. This procedure has been successfully applied in 137 patients.}, }
@article {pmid7017019, year = {1981}, author = {Guiot, HF and van der Meer, JW and van Furth, R}, title = {Selective antimicrobial modulation of human microbial flora: infection prevention in patients with decreased host defense mechanisms by selective elimination of potentially pathogenic bacteria.}, journal = {The Journal of infectious diseases}, volume = {143}, number = {5}, pages = {644-654}, doi = {10.1093/infdis/143.5.644}, pmid = {7017019}, issn = {0022-1899}, mesh = {Adolescent ; Adult ; Aged ; Anemia, Aplastic/drug therapy ; Anti-Bacterial Agents/*therapeutic use ; Bacteria/*pathogenicity ; Bacterial Infections/mortality/*prevention &amp; control ; Bone Marrow Transplantation ; Feces/microbiology ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Middle Aged ; Mouth Diseases/drug therapy ; *Patient Isolation ; Pharyngitis/drug therapy ; Rectal Diseases/drug therapy ; }, abstract = {To reduce the frequency and severity of bacterial infection, selective antimicrobial modulation (SAM) was applied in 39 patients with severely decreased host defense mechanisms. The objective was to eliminate potentially pathogenic aerobic microorganisms with minimal disturbance of the normal anaerobic bacterial flora. Elimination of potentially pathogenic aerobic microorganisms was easily accomplished in patients not infected at hospitalization. The anaerobic flora seemed to be undisturbed, and selection of or overgrowth with resistant microorganisms did not occur. The microbiologic results of the SAM regimen correlated with the incidence of infection. Only three major infections occurred in 23 patients who were free of potentially pathogenic microorganisms; 10 major infections occurred in 16 patients who were not free of potential pathogens. Seven of these 10 infections were present at hospitalization. The incidence of major infections was 47% in the patients on the SAM regimen and 82% in a group of control patients with a similar risk of infection.}, }
@article {pmid6453533, year = {1981}, author = {Schmidt, RE and Nelson, JS and Johnson, EM}, title = {Experimental diabetic autonomic neuropathy.}, journal = {The American journal of pathology}, volume = {103}, number = {2}, pages = {210-225}, pmid = {6453533}, issn = {0002-9440}, support = {732 NS06115-0/NS/NINDS NIH HHS/United States ; AM-19645/AM/NIADDK NIH HHS/United States ; HL-20604/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Autonomic Nervous System/*pathology ; Choline O-Acetyltransferase/analysis ; Colon/enzymology/innervation ; Diabetes Mellitus, Experimental/enzymology/*pathology ; Diabetic Neuropathies/enzymology/*pathology ; Dopamine beta-Hydroxylase/analysis ; Ileum/enzymology ; Male ; Mesentery/innervation ; Rats ; Rats, Inbred Lew ; Rats, Inbred WF ; Spleen/innervation ; Streptozocin ; }, abstract = {The regular occurrence of autonomic neuropathy, colonic dilatation, and loss of fecal consistency was investigated in streptozotocin-diabetic, age-matched control, and pancreatic-islet--transplanted rats using ultrastructural, histochemical, and biochemical methods. Degenerating unmyelinated axons were observed by electron microscopy in the colonic submucosa and muscularis, ileal mesentery, and splenic pedicle in 5--7 months diabetic animals; similar changes were not found in control rats or animals subjected to islet transplantation three weeks after induction of diabetes and sacrificed 4--6 months later (colon only). Regenerative changes, including axons with identifiable growth cones, were demonstrated in the mesenteric nerves of chronically diabetic animals. Formaldehyde-induced catecholamine fluorescence and cholinesterase histochemistry suggested deficiencies in colonic adrenergic and cholinergic innervation; histochemical findings in islet-transplanted animals were comparable to those of untreated control animals. Biochemical measurements of the adrenergic and cholinergic nervous system marker enzymes dopamine-beta-hydroxylase and choline acetyltransferase, respectively, in colon and spleen confirm a deficit in adrenergic (colon and spleen) and cholinergic (colon) innervation in chronically diabetic animals.}, }
@article {pmid7232319, year = {1981}, author = {Schärli, AF}, title = {[The treatment of rectal incontinence with the gracilis transposition (author's transl)].}, journal = {Schweizerische Rundschau fur Medizin Praxis = Revue suisse de medecine Praxis}, volume = {70}, number = {15}, pages = {688-692}, pmid = {7232319}, issn = {1013-2058}, mesh = {Adult ; Child ; Fecal Incontinence/psychology/*surgery ; Humans ; Methods ; Muscles/*transplantation ; *Transplantation, Autologous ; }, }
@article {pmid7232318, year = {1981}, author = {Nöthiger, F and Oesch, I}, title = {[Replacement of the anal sphincter (author's transl)].}, journal = {Schweizerische Rundschau fur Medizin Praxis = Revue suisse de medecine Praxis}, volume = {70}, number = {15}, pages = {683-687}, pmid = {7232318}, issn = {1013-2058}, mesh = {Anal Canal/*abnormalities/injuries ; Fecal Incontinence/*surgery ; Humans ; Muscle, Smooth/transplantation ; Muscles/transplantation ; Surgery, Plastic ; Transplantation, Autologous ; }, }
@article {pmid6972017, year = {1981}, author = {Cavina, E and Seccia, M and Evangelista, G}, title = {[Neosphincter and neostomy: new surgical technics as a function of the prospects of electrostimulation for continence. Clinical experience. Preliminary reports].}, journal = {Minerva chirurgica}, volume = {36}, number = {6}, pages = {389-392}, pmid = {6972017}, issn = {0026-4733}, mesh = {*Colostomy ; *Electric Stimulation Therapy ; Fecal Incontinence/*surgery ; Humans ; Muscles/*transplantation ; Perineum/*surgery ; Transplantation, Autologous ; }, }
@article {pmid7282058, year = {1981}, author = {Holschneider, AM and Hecker, WC}, title = {[Flapped and free muscle transplantation in the treatment of anal incontinence (author's transl)].}, journal = {Zeitschrift fur Kinderchirurgie : organ der Deutschen, der Schweizerischen und der Osterreichischen Gesellschaft fur Kinderchirurgie = Surgery in infancy and childhood}, volume = {32}, number = {3}, pages = {244-258}, doi = {10.1055/s-2008-1063267}, pmid = {7282058}, issn = {0174-3082}, mesh = {Adolescent ; Anal Canal/surgery ; Child ; Fecal Incontinence/*surgery ; Humans ; Infant ; Intestinal Atresia/surgery ; *Surgical Flaps ; }, abstract = {49 patients with continence-improving operations were reviewed. 41 children underwent a gracilis-transplantation according to Pickrell, 6 patients a free muscle transplantation according to Hakelius/Grotte and 2 patients a smooth muscle graft according to Schmidt. The clinical and manometrical results were compared with data from the literature. Furthermore a new technique of smooth muscle transplantation in the young infant is described. During an abdomino-sacroperineal pull-through procedure a flapped smooth muscle transplantation is performed simultaneously. The circular and longitudinal muscle layer of the pulled-through colon will be turned back and is fixed on the serosa under light tension. Afterwards the whole muscle cuff is repulled into the puborectalis sling. Examinations of the anorectal pressure as well as X-ray investigations showed a good function of the newly-established internal anal sphincter equivalent.}, }
@article {pmid7007730, year = {1981}, author = {Flint, LM and Calhoun, JH and Anderson, MD and Richardson, JD}, title = {Studies of peritoneal phagocytes as therapy for fecal peritonitis.}, journal = {The Journal of surgical research}, volume = {30}, number = {2}, pages = {154-158}, doi = {10.1016/0022-4804(81)90007-x}, pmid = {7007730}, issn = {0022-4804}, mesh = {Animals ; Ascitic Fluid/*cytology ; Escherichia coli Infections/therapy ; Feces/*microbiology ; Humans ; Male ; Peritonitis/*therapy ; Phagocytes/*transplantation ; Rats ; Staphylococcal Infections/therapy ; Transplantation, Homologous ; }, }
@article {pmid7231256, year = {1981}, author = {Hugh, TB and O'Connor, TW and Ralston, M}, title = {Pseudomembranous colitis with sparing of transplanted colon.}, journal = {The Medical journal of Australia}, volume = {1}, number = {2}, pages = {81-82}, doi = {10.5694/j.1326-5377.1981.tb135329.x}, pmid = {7231256}, issn = {0025-729X}, mesh = {Colon/pathology/*transplantation ; Enterocolitis, Pseudomembranous/complications/*pathology ; Esophageal Stenosis/pathology/*surgery ; Esophagus/pathology ; Female ; Humans ; Middle Aged ; Rectum/pathology ; Transplantation, Autologous ; }, abstract = {There is strong evidence that pseudomembranous colitis (PMC) is caused by the toxin of Clostridium difficile. A case of PMC which occurred in a patient who underwent colon interposition for a benign oesophageal stricture is presented, which had all the features of a florid PMC, but the changes were confined to the normally sited colon, and did not occur in the interposed loop. No similar case report could be found in the literature. This case is in accord with the view that PMC is produced by the toxin of local faecal bacteria, and its occurrence is precluded by removal of the colon from the faecal stream.}, }
@article {pmid7449649, year = {1981}, author = {Schmidt, E}, title = {[Plastic surgery for sphincter continence (author's transl)].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {106}, number = {1}, pages = {12-14}, doi = {10.1055/s-2008-1070247}, pmid = {7449649}, issn = {0012-0472}, mesh = {Adolescent ; Adult ; Aged ; Anal Canal/surgery ; Child ; *Colostomy ; Fecal Incontinence/*surgery ; Humans ; Methods ; Middle Aged ; Muscle, Smooth/transplantation ; Postoperative Complications ; Transplantation, Autologous ; }, abstract = {Free transplanted intestinal smooth muscle was used for plastic surgery of the sphincter in 137 patients. In 113 patients closure and continence were possible so that a colostomy bag could be avoided. The continence rate was thus 82.5%. Slight parastomal infection occurred in 15 patients. However, this did not affect continence.}, }
@article {pmid7471957, year = {1980}, author = {Köle, W and Zmugg, P}, title = {[Long-term experiences with sphincteroplasty using the Wreden-Stone method in the management of ano-rectal incontinence].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {51}, number = {12}, pages = {789-793}, pmid = {7471957}, issn = {0009-4722}, mesh = {Adult ; Anal Canal/*surgery ; Electromyography ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Manometry ; Methods ; Muscle, Smooth/transplantation ; Transplantation, Autologous ; }, abstract = {After showing the reasons for anorectal incontinence and describing the different methods of surgical treatment, the sphincterplasty technique according to Wreden-Stone is presented, as modified by the author in 1962: (1) a greater distance from the incision to the anus helps to reduce the risk of infection; (2) the strip of fascia lata winding around the anal canal is sutured to the musculus gluteus maximus on both sides. The functional results of the nine patients operated on by this method were subjectively much better than the objective results yielded by electro-myographic and manometric examinations; for only one patient were both kinds of results poor. Other methods are also discussed. At present the new treatment using smooth muscle from the large intestine is preferred, possibly combined with the sphincterplasty presented and additional use of striated muscle.}, }
@article {pmid7192301, year = {1980}, author = {Sandford, GR and Merz, WG and Wingard, JR and Charache, P and Saral, R}, title = {The value of fungal surveillance cultures as predictors of systemic fungal infections.}, journal = {The Journal of infectious diseases}, volume = {142}, number = {4}, pages = {503-509}, doi = {10.1093/infdis/142.4.503}, pmid = {7192301}, issn = {0022-1899}, support = {CA06973/CA/NCI NIH HHS/United States ; CA17970/CA/NCI NIH HHS/United States ; }, mesh = {Aspergillus/isolation &amp; purification ; Candida/isolation &amp; purification ; Cryptococcus/isolation &amp; purification ; Feces/microbiology ; Fungi/*isolation &amp; purification ; Humans ; Lung/microbiology ; Mycoses/*diagnosis ; Urine/microbiology ; }, abstract = {Fungal surveillance cultures consisting of urine, stool, and respiratory specimens were analyzed from 37 recipients of bone-marrow transplants and 52 patients undergoing chemotherapy for acute leukemia and other hematologic malignancies. All patients had prolonged aplasia. Sixty-seven percent of the patients were colonized by Candida albicans, and 28% were colonized by Candida tropicalis. No patient was colonized with any species of Aspergillus. There were 21 proven systemic fungal infections: three due to C. albicans, 16 due to C. tropicalis, and two due to Aspergillus. Positive surveillance data for C. tropicalis correlate with disease. Multiple positive-culture data yielded high predictive values (67%-83%), and single positive-culture data yielded slightly lower values as a function of body site. Positive surveillance data for C. albicans did not correlate with disease; negative culture data correlate with the absence of systemic disease due to C. tropicalis and C. albicans. Thus, surveillance data for specific fungal species can aid in diagnosis and appropriate therapy.}, }
@article {pmid7217648, year = {1980}, author = {Flavell, DJ and Pattanapanyasat, K and Flavell, SU}, title = {Opisthorchis viverrini: partial success in adoptively transferring immunity with spleen cells and serum in the hamster.}, journal = {Journal of helminthology}, volume = {54}, number = {3}, pages = {191-197}, doi = {10.1017/s0022149x0000657x}, pmid = {7217648}, issn = {0022-149X}, mesh = {Animals ; Cricetinae ; Female ; Immune Sera/*pharmacology ; *Immunization, Passive ; Male ; Mesocricetus ; Opisthorchiasis/*immunology ; Opisthorchis/physiology ; Parasite Egg Count ; Spleen/*immunology/transplantation ; Transplantation, Homologous ; }, abstract = {Three groups of golden Syrian hamsters received intraperitoneally either, (1) 1 x 10(7) spleen cells, (2) 0.5 ml. serum or, (3) 1 x 10(7) spleen cells plus 0.5 ml. serum, from donors infected 6 weeks previously with 25 Opisthorchis viverrini metacercariae, one day before and at the same time as challenge with 25 metacercariae. Three groups of control animals received the same quantities of spleen cells, serum or an admixture of both from normal non-infected donors in the same manner followed by challenge with 25 metacercariae. Animals were killed six weeks after challenge, livers and extrahepatic biliary systems carefully removed, and liver worm burdens estimated. Additionally, parasitic egg counts were performed on pooled faeces samples collected one hour prior to death. Animals receiving spleen cells, serum, or an admixture of both, from normal non-infected donors had mean worm burdens of 11.44, 12.00 and 12.66, respectively. Animals receiving spleen cells, serum, or both, from infected donors had mean worm burdens of 9.88, 7.77 and 12.00, respectively. There were no significant differences in mean worm burdens between control and experimental groups. However, a substantial reduction in parasitic faecal egg counts and subsequently mean egg production per worm was observed in all 3 groups of animals receiving spleen cells, serum, or both, from infected donors when compared to their respective control groups. These findings are discussed in relation to adoptive transfer studies performed with other helminths and their possible relevance to naturally acquired immunity is commented on.}, }
@article {pmid7388808, year = {1980}, author = {Lundholm, K and Edström, S and Karlberg, I and Ekman, L and Scherstén, T}, title = {Relationship of food intake, body composition, and tumor growth to host metabolism in nongrowing mice with sarcoma.}, journal = {Cancer research}, volume = {40}, number = {7}, pages = {2516-2522}, pmid = {7388808}, issn = {0008-5472}, mesh = {Animals ; *Body Composition ; Body Weight ; Diet ; *Eating ; Feces/analysis ; Female ; Male ; Methylcholanthrene ; Mice ; Neoplasm Transplantation ; Sarcoma, Experimental/chemically induced/*pathology ; Transplantation, Homologous ; }, }
@article {pmid7396282, year = {1980}, author = {Gierup, J and Hakelius, L}, title = {Free autogenous muscle transplantation in the treatment of anal incontinence.}, journal = {Anales espanoles de pediatria}, volume = {13}, number = {4}, pages = {339-340}, pmid = {7396282}, issn = {0302-4342}, mesh = {Adolescent ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Muscles/*transplantation ; Rectum/*surgery ; Transplantation, Autologous/*methods ; }, }
@article {pmid7388204, year = {1980}, author = {Ben-Hur, N and Gilai, A and Golan, J and Sagher, U and Issac, M}, title = {Reconstruction of the anal sphincter by gracilis muscle transfer: the value of electromyography in the preoperative assessment and postoperative management of the patient.}, journal = {British journal of plastic surgery}, volume = {33}, number = {2}, pages = {156-160}, doi = {10.1016/0007-1226(80)90004-1}, pmid = {7388204}, issn = {0007-1226}, mesh = {Adult ; Anal Canal/physiopathology/*surgery ; Biofeedback, Psychology ; *Electromyography ; Fecal Incontinence/etiology/*surgery ; Humans ; Male ; Meningomyelocele/complications ; Muscles/*transplantation ; Postoperative Care ; Preoperative Care ; Sacrococcygeal Region ; Transplantation, Autologous ; }, }
@article {pmid6989325, year = {1980}, author = {Wells, MM and Golitz, LE and Bender, BJ}, title = {Erythropoietic protoporphyria with hepatic cirrhosis.}, journal = {Archives of dermatology}, volume = {116}, number = {4}, pages = {429-432}, pmid = {6989325}, issn = {0003-987X}, mesh = {Adult ; Cholestasis/etiology ; Erythropoiesis ; Humans ; Liver/pathology ; Liver Cirrhosis/*etiology/pathology ; Liver Diseases/surgery ; Liver Transplantation ; Male ; Photosensitivity Disorders/etiology ; Porphyrias/*complications/pathology/physiopathology ; Skin/pathology ; Transplantation, Homologous ; }, abstract = {Cholestatic jaundice and rapidly deteriorating hepatic function developed in a 19-year-old man with a lifelong history of photosensitivity. Laboratory studies revealed the characteristic increased erythrocyte and fecal protoporphyrin levels of erythropoietic protoporphyria. Progressive hepatic failure was treated by orthotopic liver transplantation six months after the first clinical indication of hepatic dysfunction. Characteristic light microscopic, fluorescence microscopic, and electron microscopic findings of erythropoietic protoporphyria were present in skin and liver. Four weeks after liver transplantation, the patient died of disseminated candidiasis. At autopsy, the donor liver had no microscopic evidence of protoporphyrin accumulation, although tissue protoporphyrin levels were mildly elevated.}, }
@article {pmid6989282, year = {1980}, author = {Welch, JP and Schweizer, RT and Bartus, SA}, title = {Management of antacid impactions in hemodialysis and renal transplant patients.}, journal = {American journal of surgery}, volume = {139}, number = {4}, pages = {561-568}, doi = {10.1016/0002-9610(80)90338-4}, pmid = {6989282}, issn = {0002-9610}, mesh = {Adolescent ; Adult ; Aged ; Antacids/*adverse effects ; Child ; Colon/surgery ; Colonic Diseases/diagnostic imaging/*etiology/therapy ; Female ; Humans ; Intestinal Obstruction/diagnostic imaging/*etiology/therapy ; *Kidney Transplantation ; Male ; Middle Aged ; Radiography ; Rectum/surgery ; *Renal Dialysis ; Transplantation, Homologous ; }, abstract = {Ten cases of intestinal obstruction caused by antacid impactions in renal transplant and hemodialysis patients were added to 16 reports in the literature. In six instances, operative intervention was necessary because of failure of vigorous medical therapy. Three patients who died had perforation of the colon at sites of stercoral ulceration due to firm antacid impactions. Aggressive medical and surgical management of constipation and fecal impaction is recommended. The outlook is grim once colonic perforation has occurred.}, }
@article {pmid7362295, year = {1980}, author = {Peck, DA}, title = {Rectal mucosal replacement.}, journal = {Annals of surgery}, volume = {191}, number = {3}, pages = {294-303}, pmid = {7362295}, issn = {0003-4932}, mesh = {Adolescent ; Adult ; Child ; Colectomy ; Colitis, Ulcerative/*surgery ; Fecal Incontinence/etiology ; Female ; Humans ; Ileostomy ; Ileum/transplantation ; Intestinal Mucosa/*transplantation ; Intestinal Polyps/genetics/*surgery ; Male ; Middle Aged ; Postoperative Complications/etiology ; Rectal Neoplasms/*surgery ; Rectum/*surgery ; Transplantation, Autologous ; }, abstract = {Preservation of the rectum in chronic ulcerative colitis or familial polyposis conserves continence at the risk of recurrent disease or malignant change. Replacement of rectal mucosa with a graft of ileum in these benign colonic mucosal diseases conserves fecal continence without the threat of continuing disease or the development of carcinoma. Rectal mucosal replacement with construction of a rectal reservoir includes total colectomy, removal of the rectal mucosa-submucosa and its replacement with an ileal graft. A rectal reservoir is constructed when intestinal continuity is restored. Twenty-nine patients have undergone rectal mucosal replacement; 12 for familial polyposis and 17 for ulcerative colitis. Twenty-five patients have had intestinal continuity restored. Patients have been followed from three months to seven years after the restoration of intestinal continuity. Twenty-three patients have a satisfactory result. Fecal continence has been preserved. Patients pass an average of six stools in a 24 hour period.}, }
@article {pmid6986247, year = {1980}, author = {Kreek, MJ and Schecter, AJ and Gutjahr, CL and Hecht, M}, title = {Methadone use in patients with chronic renal disease.}, journal = {Drug and alcohol dependence}, volume = {5}, number = {3}, pages = {197-205}, doi = {10.1016/0376-8716(80)90180-5}, pmid = {6986247}, issn = {0376-8716}, mesh = {Adult ; Heroin Dependence/*rehabilitation ; Humans ; *Kidney Failure, Chronic/therapy ; Kidney Transplantation ; Male ; Methadone/adverse effects/blood/*therapeutic use ; Peritoneal Dialysis ; Renal Dialysis ; }, abstract = {Methadone disposition was studied in three patients receiving chronic methadone treatment and having chronic renal disease: one oliguric patient during peritoneal dialysis, one anuric patient on hemodialysis, and one patient following renal transplantation. In all three patients plasma levels of methadone remained within the desired therapeutic range (0.09--0.68 microgram/ml) for the doses received (40-50 mg/day). Elimination of methadone and its metabolites was almost exclusively by the fecal route in the anuric patient. Less than 1% of the daily dose was removed by peritoneal dialysis or hemodialysis. There was no laboratory or clinical evidence for accumulation of either methadone or its metabolites, suggesting that methadone is an appropriate narcotic to use in patients with renal disease.}, }
@article {pmid7442384, year = {1980}, author = {Holle, J and Freilinger, G}, title = {[Functional reconstruction of the striated sphincter muscle in the incontinent anus (author's transl)].}, journal = {Langenbecks Archiv fur Chirurgie}, volume = {351}, number = {2}, pages = {133-144}, pmid = {7442384}, issn = {0023-8236}, mesh = {Adolescent ; Adult ; Anal Canal/*surgery ; Electromyography ; Fecal Incontinence/*surgery ; Humans ; Manometry ; Middle Aged ; Muscle Contraction ; Muscles/innervation/transplantation ; Transplantation, Autologous ; }, abstract = {Anal sphincter reconstruction with muscle transplantation according to Thompson and transposition of the denervated gracilis muscle onto the surface of the pelvic floor muscles are described. The transplanted and transposed muscles are reinnervated by a collateral nerve from the adjacent functioning muscles. The follow-up examination of 16 cases of anal incontinence two years after anal sphincter reconstruction demonstrates in all but one case ontinence for firm feces and in most of them, continence for fluid feces. Reflectoric contractions of the new reconstructed sphincter can be demonstrated by myographic and manometric investigations. The advantages of dynamic sphincter reconstruction with muscular neurotization compared to other more static techniques are discussed.}, }
@article {pmid7210983, year = {1980}, author = {Schmidt, E and Bruch, HP}, title = {[Autotransplantation of smooth muscle for treating incontinence of sphincters (author's transl)].}, journal = {Zentralblatt fur Chirurgie}, volume = {105}, number = {21}, pages = {1409-1423}, pmid = {7210983}, issn = {0044-409X}, mesh = {Anal Canal/surgery ; Animals ; Dogs ; Fecal Incontinence/*surgery ; Humans ; Intestines/surgery ; Muscle, Smooth/*transplantation ; Transplantation, Autologous ; }, abstract = {By histologic, electronoptic, perfusionsmanometric and microangiographic examination it was demonstrated, that the smooth muscle of the intestinal tract can be autotransplanted and can function as a sphincter after healing. This procedure has been successfully applied is 86 patients.}, }
@article {pmid6451263, year = {1980}, author = {Berthelot, A and Pernot, F and Schleiffer, R and Gairard, A}, title = {[Autograft parathyroids and evolution of calcium parameters in thyroparathyroidectomized DOCA + NaCl treated rats].}, journal = {Comptes rendus des seances de la Societe de biologie et de ses filiales}, volume = {174}, number = {6}, pages = {1034-1040}, pmid = {6451263}, issn = {0037-9026}, mesh = {Animals ; Calcium/*metabolism ; Desoxycorticosterone/*pharmacology ; Feces/analysis ; Kinetics ; Male ; Parathyroid Glands/physiology/*transplantation ; Rats ; Sodium Chloride/*pharmacology ; *Thyroidectomy ; Transplantation, Autologous ; }, abstract = {Autografted parathyroids in thyroparathyroidectomized rats reestablished normal calcemia, increased calciuria, but calcium balance remained unchanged. DOCA + Saline effects on calcium metabolism (calciuria and positive calcium balance both increased) are found only when parathyroid and thyroid are present.}, }
@article {pmid551159, year = {1979}, author = {Raffensperger, J}, title = {The gracilis sling for fecal incontinence.}, journal = {Journal of pediatric surgery}, volume = {14}, number = {6}, pages = {794-797}, doi = {10.1016/s0022-3468(79)80267-5}, pmid = {551159}, issn = {0022-3468}, mesh = {Adolescent ; Child ; Fecal Incontinence/*surgery ; Humans ; Methods ; Muscles/*transplantation ; Postoperative Care ; Transplantation, Autologous ; }, abstract = {During the past 20 yr, we have transplanted the gracilis muscle to the perianal position for use as a sphincter to achieve continence in 7 completely incontinent children, ages 7 to 16 yr. Complete continence was achieved in three, three were improved and one transplant became infected and failed completely. The procedure has been performed as originally described by Pickrell. The bowel must be impeccably clean prior to the operation and the muscle must be sutured as tightly as possible about the anus. These two details, in addition to postoperative training, are essential for a successful result.}, }
@article {pmid369795, year = {1979}, author = {Schmidt, E and Bruch, HP and Greulich, M and Rothhammer, A and Romen, W}, title = {[Continent colostomy through free transplantation of autologous colon muscles].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {50}, number = {2}, pages = {96-100}, pmid = {369795}, issn = {0009-4722}, mesh = {Animals ; Colon ; Colostomy/*methods ; Dogs ; Fecal Incontinence/*prevention &amp; control ; Humans ; Muscle, Smooth/*transplantation ; Suture Techniques ; *Transplantation, Autologous ; }, abstract = {The study is concerned with a problem which is to a great extent still surgically unsolved, namely that of the incontinent hollow organ occlusion. We report on our own experiments on animals and on physiologicofunctional studies, which reveal the suitability of the smooth muscles as an ideal material for sphincter replacements. By histologic research it became obvious that autotransplantations of smooth muscles, carried out for the first time by the Department of Surgery of the University of Würzburg, are possible without significant tissue changes. The transplant is soon supplied by vessels which sprout ubiquitously and completely permeate it so that it can take over its function as sphincter. Meanwhile, the experience gained in experiments on animals has been transferred to surgery on humans. Incontinence and incontinence of the preternatural anus were eliminated in the first operations using autologous autotransplanted sphincteroplasties.}, }
@article {pmid521219, year = {1979}, author = {Moretti, JL and Rapin, JR and Hamberger, C and Lautie, JP and Mathieu, E and Renault, H}, title = {Radiopharmacological studies of 125I-labeled ifosfamide in rats.}, journal = {International journal of nuclear medicine and biology}, volume = {6}, number = {3}, pages = {145-151}, doi = {10.1016/0047-0740(79)90029-9}, pmid = {521219}, issn = {0047-0740}, mesh = {Animals ; Antineoplastic Agents/*metabolism ; Cyclophosphamide/*analogs &amp; derivatives ; Feces/analysis ; Ifosfamide/blood/*metabolism/urine ; Iodine Radioisotopes ; Kidney/metabolism ; Liver/metabolism ; Male ; Mice ; Neoplasm Transplantation ; Rats ; Sarcoma, Experimental/*metabolism ; Thyroid Gland/metabolism ; }, }
@article {pmid487513, year = {1979}, author = {Mollard, P and Valla, V and Jaubert De Beaujec, M}, title = {[Incontinence after repair of imperforate anus : treatment by a free muscle transplant (author's transl)].}, journal = {Chirurgie pediatrique}, volume = {20}, number = {3}, pages = {205-208}, pmid = {487513}, issn = {0180-5738}, mesh = {Anus, Imperforate/*surgery ; Fecal Incontinence/*etiology/surgery ; Humans ; Infant, Newborn ; Male ; Methods ; Muscles/surgery ; *Postoperative Complications ; }, abstract = {A case of severe anal incontinence after multiple surgical repairs for ano-rectal imperforation is presented. A successful formation of a new puborectalis sling by means of free autogenous palmaris longus muscle transplantation according to Hakeliuis is reported. The clinical success is confirmed radiologically and electromyographically. The authors discussed the principles and the results of this new method. They believe that this case pleads in favour of true muscle autotransplant re-innervation.}, }
@article {pmid456123, year = {1979}, author = {Willital, GH and Meier, H and Krebs, C and Groitl, H}, title = {[Surgical technic to alleviate anal incontinence using a magnetic anal closure].}, journal = {Chirurgisches Forum fur experimentelle und klinische Forschung}, volume = {}, number = {}, pages = {157-159}, pmid = {456123}, issn = {0303-6227}, mesh = {Anal Canal/*surgery ; Child ; Fecal Incontinence/*therapy ; Female ; Humans ; Magnetics ; *Menstrual Hygiene Products ; }, abstract = {Available operative procedures to reduce incontinence are gracilis transplant, levator plastic, free muscle transplantation and pacemakers. Further procedures being tested in clinical trials are electronic cuffs, modified Scott's sphincters, and implantation of cuffs of unstriated muscle. The magnetic anal ring, which has been developed in Erlangen, consists of two halves. Using a sacral approach both parts can be placed around the rectum without opening the bowels. An anal tampon consisting of a magnetic tampon and a tampon covering is responsible for occlusion. The tampon covering consists of polyvinylformalfoam, which guarantees an excellent plugging. Application is similar to tampons for menstruation; tampons can be changed three times a day and the bowel can be emptied normally when a change is made. In order to work successfully the tampon is pressure adapted to the pressure profile of the large bowel. Histologic investigations of the mucosa did not show any alterations. Megacolon or megarectum proximal to the anal ring did not occur.}, }
@article {pmid428265, year = {1979}, author = {Prochiantz, A and Gross, P}, title = {[Gluteal myoplasty for restoring sphincteral competence].}, journal = {Chirurgie; memoires de l'Academie de chirurgie}, volume = {105}, number = {1}, pages = {47-50}, pmid = {428265}, issn = {0001-4001}, mesh = {Adult ; Anal Canal/abnormalities/surgery ; Buttocks/*surgery ; Child ; Fecal Incontinence/*surgery ; Female ; Humans ; Infant ; Male ; Methods ; Muscles/*surgery/transplantation ; Rectum/abnormalities/surgery ; Sacrum/abnormalities ; Transplantation, Autologous ; }, }
@article {pmid367549, year = {1978}, author = {Archibald, SD and Jirsch, DW and Bear, RA}, title = {Gastrointestinal complications of renal transplantation. 2. The colon.}, journal = {Canadian Medical Association journal}, volume = {119}, number = {11}, pages = {1301-5, 1309}, pmid = {367549}, issn = {0008-4409}, mesh = {Adolescent ; Adult ; Cadaver ; Colitis/etiology ; Colon/blood supply ; Colonic Diseases/*etiology ; Female ; Follow-Up Studies ; Humans ; Intestinal Perforation/etiology ; Ischemia/etiology ; *Kidney Transplantation ; Male ; Middle Aged ; *Postoperative Complications ; Transplantation, Homologous ; }, abstract = {In 95 consecutive cases of cadaveric renal transplantation followed up for 1 to 83 months (mean 23.1 months) seven colonic complications developed in seven patients; these included ischemic colitis in three, colonic perforation in two, fecal impaction in one and appendicitis in one. Except for appendicitis all the complications occurred within 2.5 months of transplantation and were not related to the patient's age, sex, blood group, or use of cigarettes or alcohol, the duration of hemodialysis before transplantation, the tissue match or the number of infusions of immunosuppressive medication. Two patients died, but not of the complication. In the management of free colonic perforation prompt resection or exteriorization, with avoidance of intraperitoneal suture lines, and continuous postoperative peritoneal lavage may be lifesaving. Early surgical intervention and creation of a colostomy in one of the cases of ischemic colitis proved helpful.}, }
@article {pmid368986, year = {1978}, author = {Thompson, WM and Meyers, W and Seigler, HF and Rice, RP}, title = {Gastrointestinal complications of renal transplantation.}, journal = {Seminars in roentgenology}, volume = {13}, number = {4}, pages = {319-328}, doi = {10.1016/0037-198x(78)90018-4}, pmid = {368986}, issn = {0037-198X}, mesh = {Digestive System/diagnostic imaging ; Esophagitis, Peptic/diagnostic imaging ; Fecal Impaction/diagnostic imaging ; Gastrointestinal Diseases/*complications/diagnostic imaging ; Gastrointestinal Hemorrhage/diagnostic imaging ; Humans ; *Kidney Transplantation ; Mycoses/diagnostic imaging ; Pancreatitis/diagnostic imaging ; *Postoperative Complications ; Radiography ; Stomach Ulcer/diagnostic imaging ; }, }
@article {pmid361355, year = {1978}, author = {Schiller, U}, title = {[Corrective surgery in sensory anal incontinence].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {49}, number = {10}, pages = {645-647}, pmid = {361355}, issn = {0009-4722}, mesh = {Fecal Incontinence/*surgery ; Humans ; Male ; Middle Aged ; Sensory Receptor Cells ; *Skin Transplantation ; Surgery, Plastic/methods ; }, }
@article {pmid646498, year = {1978}, author = {Smith, EI and Tunell, WP and Williams, GR}, title = {A clinical evaluation of the surgical treatment of anorectal malformations (imperforate anus).}, journal = {Annals of surgery}, volume = {187}, number = {6}, pages = {583-592}, pmid = {646498}, issn = {0003-4932}, mesh = {Anus, Imperforate/*surgery ; Child ; Child, Preschool ; Constriction, Pathologic/etiology ; Evaluation Studies as Topic ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Methods ; Perineum/transplantation ; Postoperative Complications ; Preoperative Care ; Rectal Diseases/etiology ; Rectum/*abnormalities/surgery ; Transplantation, Autologous ; }, abstract = {The surgical correction of anorectal malformations remains a serious problem despite their relatively frequent occurrence. Our surgical experience with 90 patients, seen in the past ten years, includes abdominal-perineal or sacro-abdominal-perineal repair in 28 patients, complete perineal anoplasty in 13 patients, and "cut-back" perineal anoplasty in 38 patients. Secondary surgical procedures for "fecal reservoir syndrome" (seven patients), revision for stricture (11 patients) and excision of redundant mucous membrane (ten patients). The observations made from this clinical study are: 1) The importance of thorough urological and neurological evaluation of "high" abnormalities and the value of the cremasteric and bulbocavernosus reflexes as indicators of sacral innervation. 2) Increasing satisfaction with the "cut-back" anoplasty as a definitive procedure or as a temporary stage in low recto-vaginal or recto-vestibular fistulas. The technique for the "cut-back" is improved by the use of Burow's triangles and the use of nonabsorbable sutures. 3) The advisability of the complete perineal anoplasty with posterior positioning of the anus and construction of a perineal body in patients with low recto-vaginal and recto-vestibular fistulas. 4) A concern over the functional capacity of the distal bowel segment in high abnormalities. This is emphasized by the experience with six secondary resections of the rectosigmoid or left colon for "fecal reservoir syndrome." 5) Heartening results with secondary operations for stricture and redundant mucous membrane which suggest the desirability of an earlier surgical approach to these complications.}, }
@article {pmid648269, year = {1978}, author = {Schmidt, E}, title = {[Surgical management of anus incontinence using free-transplanted autologous, endogenous intestinal musculature].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {49}, number = {5}, pages = {320-321}, pmid = {648269}, issn = {0009-4722}, mesh = {Anal Canal/*surgery ; Colon ; Fecal Incontinence/*surgery ; Humans ; Methods ; Muscle, Smooth/*transplantation ; Transplantation, Autologous ; }, abstract = {A new treatment for anal incontinence is presented. Smooth muscle from the large intestine is transplanted to form a new sphincter. The advantage of using smooth muscle as a sphincter plastic id discussed.}, }
@article {pmid633058, year = {1978}, author = {Hakelius, L and Gierup, J and Grotte, G and Jorulf, H}, title = {A new treatment of anal incontinence in children: free autogenous muscle transplantation.}, journal = {Journal of pediatric surgery}, volume = {13}, number = {1}, pages = {77-82}, doi = {10.1016/s0022-3468(78)80216-4}, pmid = {633058}, issn = {0022-3468}, mesh = {Adolescent ; Anal Canal/*abnormalities ; Child ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Methods ; Muscles/*transplantation ; Rectum/*abnormalities ; Transplantation, Autologous ; }, abstract = {A new method is presented for the treatment of anal incontinence in children, including free autogenous muscle transplantation. The primary step is denervation of a skeletal muscle, which 2 wk later is transplanted and placed as a U-sling around the rectum, imitating the position and function of the puborectalis muscle. The transplant is placed in close contact with innervated muscles, which act as reinnervation sources. The results in five consecutive patients are highly promising. An early sign of improvement is the occurrence of a sensation of rectal fullness. All the patients reached an acceptable degree of continence, including abandonment of the use of napkins, 4-12 mo after surgery.}, }
@article {pmid631654, year = {1978}, author = {Skácel, V and Laichman, S and Gatĕk, J}, title = {Notes on replacement of the anal sphincters by muscle.}, journal = {Folia morphologica}, volume = {26}, number = {1}, pages = {61-64}, pmid = {631654}, issn = {0015-5640}, mesh = {Anal Canal/*surgery ; Cadaver ; Fecal Incontinence/*surgery ; Humans ; Muscles/*transplantation ; Transplantation, Autologous ; }, }
@article {pmid358095, year = {1978}, author = {Marty, M and Gisselbrecht, C and Gluckman, E and Devergie, A and Bussel, A and Ducluzeau, R and Perol, AM}, title = {Gut sterilization during bone marrow transplantation [proceedings].}, journal = {Pathologie-biologie}, volume = {26}, number = {1}, pages = {60}, pmid = {358095}, issn = {0369-8114}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Blood/microbiology ; *Bone Marrow Transplantation ; Feces/microbiology ; Humans ; Intestines/*microbiology ; }, }
@article {pmid561708, year = {1977}, author = {Vatin, AE and Popova, GE and Averina, SA}, title = {[Pharmacokinetics of 35S-tomizin in mice with leukemia L-1210].}, journal = {Farmakologiia i toksikologiia}, volume = {40}, number = {4}, pages = {475-478}, pmid = {561708}, issn = {0014-8318}, mesh = {Animals ; Antibody-Producing Cells/drug effects ; Antineoplastic Agents/*metabolism ; Biotransformation ; Leukemia L1210/*metabolism ; Male ; Mice ; Neoplasm Transplantation ; Thiazines/*metabolism/pharmacology ; }, abstract = {A comparative study of the distribution of 35S-tomisin in the organism of intact (without neoplasia) mice and those with L-1210 leucosis was carried out. In both animal groups the tagged drug was found to be largely accumulating early after its introduction in the tissues of the liver, kidneys, intestines, spleen and lymph nodes. In 30 minutes time following introduction of 35-S-tomison 7.3 +/- 0.7 per cent of its amount was detected in the ascitic fluid. On centrifugation of the tagged drug its bulk (92-95 per cent) remained in the supernatant fluid. During the first 24 hours the drug leaves the body: 25-35 per cent with urine, 3-5 per cent--with feces and 0.1-0.3 per cent--with bile. In the urine of mice with leucosis the products of the 35S-tomisin biotransformation appear earlier than in intact animals. The most marked immunodepressive effect of tomisin was marked with its administration 24 and 48 hours after immunization.}, }
@article {pmid327795, year = {1977}, author = {Bartolomeo, RS and Calabrese, PR and Taubin, HL}, title = {Spontaneous perforation of the colon. A potential complication of chronic renal failure.}, journal = {The American journal of digestive diseases}, volume = {22}, number = {7}, pages = {656-657}, pmid = {327795}, issn = {0002-9211}, mesh = {Adult ; Colonic Diseases/*etiology ; Fecal Impaction/*complications ; Female ; Humans ; Intestinal Perforation/*etiology ; Kidney Failure, Chronic/*complications/therapy ; Kidney Transplantation ; Renal Dialysis ; Transplantation, Homologous ; }, }
@article {pmid321799, year = {1977}, author = {Siemens, R and Flint, LM}, title = {Traumatic hemipelvectomy: a case report.}, journal = {The Journal of trauma}, volume = {17}, number = {3}, pages = {245-247}, pmid = {321799}, issn = {0022-5282}, mesh = {Adult ; Amputation, Traumatic/*surgery ; Debridement ; Humans ; Leg Injuries/*surgery ; Male ; Pelvis/*injuries ; Skin Transplantation ; Transplantation, Autologous ; Urinary Diversion ; }, abstract = {Traumatic hemipelvectomy is a devasting injury which few patients survive. A survivor of traumatic hemipelvectomy is described. Immediate and long-term management include prompt resuscitation, vascular control, urinary and fecal diversion, wound debridement, wound closure, and physical and psychologic rehabilitation.}, }
@article {pmid866691, year = {1977}, author = {Puri, P and Nixon, HH}, title = {Long-term results of Swenson's operation for Hirschsprung's disease.}, journal = {Progress in pediatric surgery}, volume = {10}, number = {}, pages = {87-96}, pmid = {866691}, issn = {0079-6654}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; Constipation/etiology ; Diarrhea/etiology ; Fecal Incontinence/etiology ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Megacolon/*surgery ; Methods ; Postoperative Complications ; Time Factors ; Urinary Incontinence/etiology ; }, abstract = {84 of 89 cases were traced 18 to 27 years after Swenson's operation. Seven had long segments. All were alive and in good general health except one who had renal transplant for hypertension due to pyelonephritis in a residual solitary kidney. 61 are married of whom 34 have children. None of the children have Hirshsprung's disease. 48 were fully normal within one year of operation. 29 had constipation enough to require treatment. Seven had diarrhoea which in three required hospitalisation for electrolyte disturbances and dehydration. 39 had some degree of soiling, but in only nine was this troublesome. Recovery of normal bowel control was more rapid in those with a good social background. Eight had postoperative strictures, but treatment has remained successful in the long-term in seven of these. Five patients had inadequate resections and are well after further surgery. Nine had urinary incontinence of which seven had only nocturnal enuresis. All are fully recovered. Two male patients have absence of ejaculation and two females are infertile with scarred Fallopian tubes. 83 of the 84 now have normal bowel control and good health. One has a permanent ileostomy.}, }
@article {pmid617521, year = {1977}, author = {Gardner, G and Grosfeld, JL}, title = {Increased survival in fecal peritonitis treated with donor peritoneal phagocytes.}, journal = {Surgical forum}, volume = {28}, number = {}, pages = {51-53}, pmid = {617521}, issn = {0071-8041}, mesh = {Ampicillin/administration &amp; dosage/therapeutic use ; Animals ; Feces ; Macrophages/*transplantation ; Neutrophils/*transplantation ; Peritoneum ; Peritonitis/immunology/mortality/*therapy ; Phagocytes/*immunology ; Rats ; Transplantation, Homologous ; }, }
@article {pmid588694, year = {1977}, author = {Hakelius, L and Gierup, J and Grotte, G}, title = {Muscle transplant for sphincter function.}, journal = {Birth defects original article series}, volume = {13}, number = {5}, pages = {255-257}, pmid = {588694}, issn = {0547-6844}, mesh = {Child ; Child, Preschool ; Fecal Incontinence/*surgery ; Female ; Foot ; Hand ; Humans ; Male ; Muscles/*transplantation ; Rectum/*surgery ; Urethra/*surgery ; Urinary Incontinence/*surgery ; }, }
@article {pmid318813, year = {1977}, author = {Nahai, F and Lamb, JM and Havican, RG and Stone, HH}, title = {Factors involved in disruption of intestinal anastomoses.}, journal = {The American surgeon}, volume = {43}, number = {1}, pages = {45-51}, pmid = {318813}, issn = {0003-1348}, mesh = {Animals ; Cefazolin/administration &amp; dosage ; Colon/transplantation ; Dogs ; Intestinal Mucosa/microbiology ; Intestine, Large/*surgery ; Intestine, Small/*surgery ; Jejunum/transplantation ; Peritonitis/prevention &amp; control ; Surgical Wound Dehiscence/*etiology/microbiology ; Surgical Wound Infection/microbiology/prevention &amp; control ; Suture Techniques ; Transplantation, Autologous ; }, abstract = {Bowel anastomoses, as performed on 181 dogs, were studied: (1) by interposing segments of colon into small bowel and vice versa, (2) by comparing clean anastomoses to those contaminated by feces before and after suturing, (3) with and without parenteral preoperative antibiotic, and (4) with and without coaptation of an inverted serosa. All animals with a timed sacrifice as well as an unexplained death had careful autopsy. Results demonstrated no difference in the healing capacity of large (91%) versus small (92%) intestine under identical circumstances. Intraluminal bacteria were of importance only if spillage caused contamination during operation and thereby subsequent infection of the peritoneal surface of the suture line. Peritonitis preceded all 28 leaks, yet the converse never occurred. Likelihood of a complicating peritonitis (67%) and thus an anastomotic leak (24%) was significantly reduced through the preoperative administration of prophylactic cefazolin (19 and 4%, respectively). A "serosal seal" also appeared important in obviating suture line disruption. Our data emphasize the value of an inverted and serosal lined anastomosis, bowel preparatory measures, prophylactic antibiotic, and the disruptive action of local bacterial peritonitis.}, }
@article {pmid826226, year = {1976}, author = {Webbe, G and James, C and Nelson, GS and Smithers, SR and Terry, RJ}, title = {Acquired resistance to Schistosoma haematobium in the baboon (Papio anubis) after cercarial exposure and adult worm transplantation.}, journal = {Annals of tropical medicine and parasitology}, volume = {70}, number = {4}, pages = {411-424}, doi = {10.1080/00034983.1976.11687140}, pmid = {826226}, issn = {0003-4983}, mesh = {Animals ; Feces/parasitology ; Female ; Haplorhini ; *Immunity, Active ; Lung/pathology ; Male ; Papio ; Parasite Egg Count ; Schistosoma haematobium/*immunology ; Schistosomiasis/*immunology/parasitology/pathology ; Urinary Bladder/pathology ; Urine/parasitology ; }, abstract = {Observations were made on the development of acquired resistance to Schistosoma haematobium in the baboon following immunization with cercariae by the percutaneous route and by the transplantation of adult worms into the mesenteric veins. In the first experiment six baboons were immunized with 1000 S. haematobium cercariae given percutaneously. They were challenged with 10 000 cercariae given 73 weeks later and the results were compared with a similar infection in non-immunized animals. The results showed that the baboon can develop a strong resistance to reinfection with S. haematobium. The manifestations of the immunity were (i) the absence of any increase in egg output after challenge (ii) the substantially lower level of adult worms and eggs in the tissues of the immunized baboons compared with the challenge control animals (iii) a reduction in the egg laying capacity of the residual worms and (iv) the virtual absence of gross pathology and the mild lesions seen in the tissue sections of all the immunized animals. The depression in egg laying of the worms was confirmed by transplanting them into non-immune baboons. This experiment indicated that the non-egg-laying worms in the immune baboons were not irreversibly damaged since they survived, some even migrating to the vesical and ureteric vessels, and egg-laying was rapidly resumed after transplantation. A further experiment was designed to see if a similar degree of immunity could be produced by an adult worm infection without previous exposure to cercariae or schistosomula. The immunization dose consisted of 50-100 S. haematobium worm pairs which were transplanted into the mesenteric veins of each of six baboons and the animals were challenged percutaneously with 7000 cercariae 35-55 weeks later. There was little difference in the worm burdens of the immunized and control animals but the worms in the immunized baboons produced fewer eggs and the pathology seen in these animals was much milder than in the challenge control animals suggesting that some degree of resistance to reinfection was produced by the transplanted worms.}, }
@article {pmid961846, year = {1976}, author = {Hakami, M and Emamy, H and Radi, HA}, title = {Vastus internus muscle transplant for the correction of anal incontinence: report of a case.}, journal = {American journal of proctology}, volume = {27}, number = {4}, pages = {50-52}, pmid = {961846}, issn = {0002-9521}, mesh = {Adult ; Anal Canal/*surgery ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Muscles/*transplantation ; Transplantation, Homologous ; }, }
@article {pmid781315, year = {1976}, author = {Aguilo, JJ and Zincke, H and Woods, JE and Buckingham, JM}, title = {Intestinal perforation due to fecal impaction after renal transplantation.}, journal = {The Journal of urology}, volume = {116}, number = {2}, pages = {153-155}, doi = {10.1016/s0022-5347(17)58726-1}, pmid = {781315}, issn = {0022-5347}, mesh = {Adult ; Cathartics/therapeutic use ; Colonic Diseases/etiology ; Diverticulum, Colon/diagnosis ; Early Ambulation ; Fecal Impaction/*complications/prevention &amp; control ; Humans ; Immunosuppressive Agents/therapeutic use ; Intestinal Perforation/*etiology ; Jejunum ; *Kidney Transplantation ; Male ; Postoperative Complications/etiology ; Preoperative Care ; Transplantation, Homologous ; }, abstract = {Three renal allograft recipients suffered major intestinal complications shortly after the operation. Identification of diverticular disease, adequate preoperative bowel preparation, avoidance of excessive amounts of non-absorbable antacids, early ambulation, and periodic laxatives and stool softeners can prevent these complications. Surgical management includes careful inspection for additional perforations, resection and colostomy, and continuous peritoneal lavage.}, }
@article {pmid937330, year = {1976}, author = {Chrysospathis, P and Antonopoulos, D and Charitopoulos, N and Bramis, J and Dreiling, DA}, title = {"Cycloperistaltic" intestinal segment: a new method to prevent excessive fluid loss in permanent ileostomies.}, journal = {The American journal of gastroenterology}, volume = {65}, number = {4}, pages = {329-334}, pmid = {937330}, issn = {0002-9270}, mesh = {Animals ; Colitis, Ulcerative/surgery ; Dogs ; Fecal Incontinence/etiology/*prevention &amp; control ; *Gastrointestinal Motility ; Humans ; Ileostomy/adverse effects/*methods ; Ileum/transplantation ; Muscle, Smooth/surgery ; *Peristalsis ; Postoperative Complications/*prevention &amp; control ; Transplantation, Autologous ; Water-Electrolyte Imbalance/prevention &amp; control ; Wound Healing ; }, abstract = {A 10-15 cm. long isolated intestinal segment, in which peristalsis has been altered to run in a circular fashion, was interposed in a series of permanent ileostomy-bearing dogs and in two clinical cases with severe diarrhea after total colectomy. Excellent results in both patients confirmed the experimental findings. Technically the method is easily accomplished by cutting the antimesenteric site of the intestinal segment lengthwise and resuturing it transversely. Two major advantages of this technic are postulated. First, the retarding action of the isolated loop does not depend on the great variations observed in peristaltic activity of the small intestine which in some patients results in obstruction. Second, the blood supply to the loop is unlikely to be impaired. Possibly both these advantages derive from the fact that the loop is twisted only 90% instead of 180 degrees required in the ordinary reversed loop interposition.}, }
@article {pmid1253659, year = {1976}, author = {Jacob, ET and Shapira, Z and Bar-Natan, N and Berant, M}, title = {Total anorectal reconstruction following congenital anorectal anomaly: report of a case.}, journal = {Diseases of the colon and rectum}, volume = {19}, number = {2}, pages = {172-177}, doi = {10.1007/BF02590876}, pmid = {1253659}, issn = {0012-3706}, mesh = {Adult ; Anal Canal/*abnormalities/surgery ; Fecal Incontinence/surgery ; Humans ; Methods ; Muscles/surgery ; Rectum/*abnormalities/surgery ; }, abstract = {Following several unsuccessful postnatal attempts at anoplasty to correct anal atresia with a rectovaginal fistula, the patient, 20 years later, underwent an anorectal sphincteric construction using a gracilis-muscle transplant. The five-stage procedure, which extended over a period of two years, resulted in highly satisfactory continence and full social rehabilitation of the patient. The continence achieved in this case seems to be in contradiction to some of the accepted concepts of the mechanisms of continence.}, }
@article {pmid769151, year = {1976}, author = {Deucher, F}, title = {[Around the sphincter: problems of continence in surgery of the large intestine].}, journal = {Schweizerische medizinische Wochenschrift}, volume = {106}, number = {9}, pages = {273-281}, pmid = {769151}, issn = {0036-7672}, mesh = {Fecal Incontinence/*etiology/surgery ; Fissure in Ano/surgery ; Humans ; Intestine, Small/transplantation ; Liver Transplantation ; Methods ; Pancreas Transplantation ; Rectal Neoplasms/surgery ; Rectum/surgery ; }, abstract = {Anatomy and physiology of anal continence and incontinence are described. The surgeon's first main task is the prevention of incontinence, e.g. in the treatment of the small and mobile carcinoma of the rectum, the wide pedunculated papilloma, the fistula in ano, haemorrhoids and anal fissure. The second main task is the reconstruction of continence of rectal prolapse, ectropion, third grade rupture of the perineum and perineal injuries. The possibilities for reconstruction, reinforcement and replacement of the sphincter are described.}, }
@article {pmid1251036, year = {1976}, author = {Brandesky, G and Holschneider, AM}, title = {Operations for the improvement of faecal incontinence.}, journal = {Progress in pediatric surgery}, volume = {9}, number = {}, pages = {105-114}, pmid = {1251036}, issn = {0079-6654}, mesh = {Age Factors ; Anal Canal/abnormalities/surgery ; Child ; Child, Preschool ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Muscles/*surgery ; Rectum/abnormalities/surgery ; Thigh/*surgery ; }, abstract = {Experiences and results are reported of Pickrell's gracilis sling transplantation in 30 cases. 24 cases could be followed up. In 21 of these there was definite improvement of continence. The favourable results are attributed to the contractibility of the muscle after transplantation. After high anal and rectal atresiae, a maturation of anorectal structures and a belated rectal adaption reaction may be observed, which can be attributed to the gracilis sling operation. It seems, therefore to be sensible to perform the operation earlier than has been practised hitherto.}, }
@article {pmid1108814, year = {1976}, author = {Perloff, LJ and Chon, H and Petrella, EJ and Grossman, RA and Barker, CF}, title = {Acute colitis in the renal allograft recipient.}, journal = {Annals of surgery}, volume = {183}, number = {1}, pages = {77-83}, pmid = {1108814}, issn = {0003-4932}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Barium Sulfate ; Colitis/*etiology/surgery ; Colon/*blood supply ; Enema ; Female ; Humans ; Immunosuppression Therapy ; Ion Exchange Resins ; Ischemia/*etiology ; *Kidney Transplantation ; Male ; Melena/etiology ; Middle Aged ; Necrosis ; Transplantation, Homologous ; }, abstract = {Four renal allograft recipients with evidence of ischemic damage to the colon are presented and compared with 11 cases from 5 major series. Similarities in the patients included: deterioration of renal function, multiple immunosuppressive and antibiotic regimens, the use of cadaver renal allografts, and diagnostic and therapeutic measures requiring frequent enemas with barium and ion-exchange resins. Two of our patients underwent surgery for the removal of segments of necrotic colon after several weeks of fever and abdominal pain initially attributed to either acute rejection, viral infection, or pancreatitis. One patient had three days of melena and responded to non-operative therapy. The fourth patient developed ischemic colonic changes 10 weeks after allograft nephrectomy and was receiving no immunosuppression at the time. Broad spectrum antibiotics were used at various times in all patients. Early aggressive evaluation of gastrointestinal complaints--including barium enema, upper gastrointestinal series with small bowel follow-through, proctosigmoidoscopy or colonoscopy, and arteriography--is indicated, in view of the lethality of the complication of colonic ulceration. The clinical pictures presented emphasize the fact that recipients of renal allografts are commonly heir to many complications which may be considered rare in the normal population.}, }
@article {pmid1067688, year = {1976}, author = {Holle, J}, title = {[Muscular neurotization in the field of reconstructive surgery (author's transl)].}, journal = {Wiener klinische Wochenschrift. Supplementum}, volume = {48}, number = {}, pages = {3-21}, pmid = {1067688}, issn = {0300-5178}, mesh = {Anal Canal/surgery ; Animals ; Blepharoptosis/surgery ; Facial Paralysis/surgery ; Fecal Incontinence/surgery ; Humans ; Muscle Contraction ; Muscles/*innervation/*transplantation ; *Nerve Regeneration ; Oculomotor Muscles/transplantation ; Rabbits ; Surgery, Plastic/methods ; Swine ; }, abstract = {Attention is drawn in a short historical review to muscular neurotization, a surgical procedure described at the turn of the century. This term is applied to the reinnervation of paralyzed muscles by the proliferation of collateral neural axons arising in an adjacent muscle possessing normal function. The physiological basis for this procedure was expounded by eminent muscle physiologists following extensive research. The present experimental investigations on 20 Vietnamese pigs demonstrated that a defective anal sphincter muscle could be rectified by a muscle graft. This spindle-shaped muscle graft became incorporated into the anal and rectosphincteric reflex mechanism by muscular neurotization. Complete--or even parts of--muscles with parallel fibres are better suited for transplantation purposes than entire spindle-shaped or feather-like muscles. Once the edge of the muscle has been reached by the proliferating axons all the cells can be simultaneously supplied with motor end plates in the case of muscles with parallel fibres. On the other hand, the use of spindle-shaped or feather-like muscles with a diagonal arrangement of the fibres entails axon proliferation over relatively large distances to achieve reinnervation of the more distal parts of the muscle with an attendant prolongation of the reinnervation procedure and, frequently, partial loss of muscle viability. In another experiment on Vietnamese pigs the total anal sphincter was excised and replaced by the denervated, but vascular semitendinosus muscle of the right hind limb. When transposed to the pelvic floor musculature the denervated muscle becomes adequately reinnervated by muscular neurotization and at the same time adopts all the properties typical of a sphincteric muscle. The newly-formed sphincter displays changes in its enzyme pattern and becomes capable of continuous tonus; the spinal reflex arc is set up and the transplanted muscle develops characteristic metabolic and contractile properties. In another experimental series the reinnervation of paralyzed extraocular muscles by muscular neurotization was investigated in 10 rabbits. The denervated but still vascular inferior oblique muscle was successfully grafted onto the inferior rectus muscle, with obvious clinical application in future. The clinical application of muscular neurotization in surgical reconstruction is demonstrated in 4 cases, the first being one of facial palsy and the second one of blepharoptosis, whilst muscular neurotization was used in the two last cases to treat anal incontinence due to partial destruction and absence of the sphincter, respectively. In the one case a muscle graft was taken to reconstruct the anal sphincter and in the other case a new sphincter was reconstructed by transposing the denervated gracilis muscle onto the pelvic floor muscle. Both cases were eminently successful with restoration of anal continence and the rectosphincteric reflex mechanisms.}, }
@article {pmid1202414, year = {1975}, author = {Banaja, AA and James, JL and Riley, J}, title = {An experimental investigation of a direct life-cycle in Reighardia sternae (Diesing, 1864), a pentastomid parasite of the herring gull (Larus argentatus).}, journal = {Parasitology}, volume = {71}, number = {3}, pages = {493-503}, doi = {10.1017/s0031182000047259}, pmid = {1202414}, issn = {0031-1820}, mesh = {Air Sacs/parasitology ; Animals ; Arthropods/*growth &amp; development ; Bird Diseases/*parasitology ; Birds/parasitology ; Chickens ; Female ; Male ; Mice ; Parasitic Diseases/parasitology ; *Parasitic Diseases, Animal ; }, abstract = {A direct life-cycle in Reighardia sternae, a cephalobaenid pentastomid of gulls was investigated: the work was prompted by a report of eggs and larvae recovered from the stomach and intestine of a naturally infected gull. Infective pentastomid eggs were obtained by surgically transplanting maturing female Reighardia, taken from freshly shot wild gulls, into captive recipients. Faecal material from birds thus artificially infected was collected daily and examined for eggs. Eggs were force fed to 33 hand-reared (from eggs or nestlings) juvenile gulls which were selected at random and sacrificed at intervals thereafter and examined for pentastomids. One hour after infection, primary larvae appear in the body cavity where they moult immediately. They grow steadily and by 27-35 days are sexually differentiated, and by 66 days have copulated. Fertilized females take a further 116 days to produce eggs by which time they are 7-6 cm long. The complex migrations undertaken by developing larvae in the gull, and the problems of the mechanism of direct transmission, are discussed.}, }
@article {pmid174209, year = {1975}, author = {Hivet, M and Blanchon, P}, title = {[Ischemic gastric ulcer on a stomach transposed into the thorax. Treatment by aorticohepatic venous transplant].}, journal = {La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris}, volume = {51}, number = {45}, pages = {2719-2722}, pmid = {174209}, mesh = {Aged ; Aorta, Abdominal/*surgery ; Esophageal Stenosis/surgery ; Esophagoplasty/*adverse effects ; Female ; Hepatic Artery/*surgery ; Humans ; Ischemia/etiology/therapy ; Melena/etiology ; Saphenous Vein/*transplantation ; Stomach/blood supply/surgery ; Stomach Ulcer/*etiology/therapy ; Transplantation, Autologous ; }, }
@article {pmid1227923, year = {1975}, author = {Bogomolova, NS and Suskova, VS and Minakova, SM and Chernov, VA and Serebriakov, NG}, title = {[Prospidin-C14 blood level, distribution in the organs and tissues and excretion from the body of rats].}, journal = {Farmakologiia i toksikologiia}, volume = {38}, number = {6}, pages = {722-728}, pmid = {1227923}, issn = {0014-8318}, mesh = {Animals ; Carbon Radioisotopes ; Feces/analysis ; Injections, Intravenous ; Kinetics ; Male ; Neoplasm Transplantation ; Piperazines/*metabolism ; Prospidium/*metabolism/urine ; Radioactivity ; Rats ; Sarcoma, Experimental/drug therapy/metabolism ; Time Factors ; }, abstract = {Experiments were conducted on rats with sarcoma-45 and intact ones to study the prospidin-C14 content in the blood, distribution of the drug among the organs and tissues and its elimination from the organism. A single intravenous introduction of prospidin-C14 was found to be followed by its quick (in 2 hours) disappearance frob the blood. During the first 15 minutes the distribution of the drug over the organs and tissues was of a non-uniform nature and different from the distribution of other known antineoplastic agents, with relatively high concentrations of prospidin-C14 being demonstrable in the kidneys, lungs, the skin, intestine, bones, pancreas and low ones--in the liver, spleen and lymph nodes. The elimination of the drug from the organs and tissues is non-uniform. Prospidin-C14 and labeled products of its transformation are quickly (during the first 24 hours after administration) passed from the organism, chiefly with urine.}, }
@article {pmid1207318, year = {1975}, author = {Schwedler, T and Erichsen, K}, title = {[Gracilis-muscle transplant for the treatment of fecal incontinence (author's transl)].}, journal = {Langenbecks Archiv fur Chirurgie}, volume = {339}, number = {}, pages = {451-457}, pmid = {1207318}, issn = {0023-8236}, mesh = {Anal Canal/physiopathology ; Child ; Electromyography ; Fecal Incontinence/physiopathology/*surgery ; Female ; Humans ; Male ; Muscles/transplantation ; Postoperative Care ; Transplantation, Autologous ; }, abstract = {Between 1962 and 1974, 40 children were treated by transplantation of the gracilis muscle. Clinical and electromyographic follow-up studies were performed on 37 children. Results were good in 12 cases, satisfactory in 11 cases, and poor in 14. Children with myelomeningocele showed the poorest results. Four girls with ano-vestibular fistula were treated by a modified method of operation. Because of the special anatomic situation, the gracilis muscle was positioned around the dorsal rectum in a semicircle only and then fixed to the os pubis under high tension. Results were good in 3 cases and satisfactory in 1 case.}, }
@article {pmid1189451, year = {1975}, author = {Brandesky, G}, title = {[The Surgical Management of Faecal Incontinence in Childhood (author's transl)].}, journal = {Wiener klinische Wochenschrift}, volume = {87}, number = {17}, pages = {541-544}, pmid = {1189451}, issn = {0043-5325}, mesh = {Age Factors ; Anal Canal/abnormalities ; Child ; Child, Preschool ; Fecal Incontinence/*surgery ; Female ; Humans ; Male ; Meningomyelocele/surgery ; Muscle Contraction ; Muscles/transplantation ; Transplantation, Autologous ; }, abstract = {A series of 13 cases is reported in which gracilis muscle transplantation according to Pickrell was carried out. In half of the cases a modification using bilateral gracilis muscle transplants was performed. 10 children were followed up; 8 of them showed an improvement in faecal continence. Preserved contractility of the transplanted gracilis muscle seemed to be responsible for this improvement. Since maturation of anorectal structures after surgical correction of high anorectal atresias and late development of anorectal mechanisms seems possible and might to be assisted by transplantation, early surgery -- about the fourth year of life -- is recommended.}, }
@article {pmid1100919, year = {1975}, author = {Evans, EG}, title = {The incidence of pathogenic yeasts among open-heart surgery patients-the value of prophylaxis.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {70}, number = {3}, pages = {466-470}, pmid = {1100919}, issn = {0022-5223}, mesh = {Administration, Oral ; Amphotericin B/administration &amp; dosage/*therapeutic use ; Candida/isolation &amp; purification ; Candida albicans/isolation &amp; purification ; Candidiasis/*prevention &amp; control ; Cardiac Surgical Procedures/*adverse effects ; Endocarditis/*prevention &amp; control ; Evaluation Studies as Topic ; Fascia Lata/transplantation ; Feces/microbiology ; Female ; Heart Valve Diseases/surgery ; Humans ; Male ; Mouth/microbiology ; Nystatin/administration &amp; dosage/*therapeutic use ; Pessaries ; Tablets ; Transplantation, Homologous ; }, abstract = {The normal levels of commensal yeasts in patients undergoing open-heart surgery are established and the effect of antifungal prophylaxis is assessed. Mouth swabs and feces were taken for culture from patients on admission to hospital and 1,2, and 3 weeks postoperatively. Eighty-seven patients who received normal treatment and 50 patients who were given oral and topical antifungal prophylaxis commencing 12 days before hospitalization were studied. Yeast pathogens, mainly Candida albicans, were isolated from 42 (48.3 per cent) of the normal group on admission. There was a marked increase in the incidence and quantities of yeasts isolated from patients in the immediate postoperative period. The incidence and levels of yeasts in patients receiving antifungal prophylaxis was considerably reduced both on admission and postoperatively. The risk of Candida sepsis in open-heart surgery patients with high levels of commensal yeasts is discussed and the possibility of routine antifungal prophylaxis raised.}, }
@article {pmid1150381, year = {1975}, author = {Garrido, H and de Diego, JA and Cano, MC and Lucea, C and Escribano, PM and Manzanos, A}, title = {Homograft of the small intestine. Metabolic and functional changes causing irreversible shock.}, journal = {International surgery}, volume = {60}, number = {6-7}, pages = {351-354}, pmid = {1150381}, issn = {0020-8868}, mesh = {Acid-Base Equilibrium ; Animals ; Aorta/surgery ; Blood Transfusion ; Carbon Dioxide/blood ; Dextrans/therapeutic use ; Dogs ; Intestine, Small/blood supply/*transplantation ; Ischemia ; Postoperative Complications ; Shock/therapy ; Shock, Surgical/*etiology/metabolism/prevention &amp; control ; Time Factors ; Transplantation, Homologous/methods/mortality ; Vena Cava, Inferior/surgery ; Water-Electrolyte Balance ; }, abstract = {Homotransplantation of the small intestine is subject to high mortality in the first 48 hours after operation. We analyzed various causes of death, underlining the importance of postoperative shock, then developed an experiment in dogs with the object of improving the survival. We applied various therapeutic measures in order to reduce the factors which participate in the evolution of chronic, hypovolemic and toxic shock. We attempted to: (1) reduce the consecutive alterations to ischemia of the homotransplant during the non-perfusion period; (2) reduce the deleterious effect of retained fecal matter; (3) reduce the metabolic acidosis secondary to clamping of the great vessels; (4) acknowledge, analyze and correct alterations in fluid and electrolyte balances; (5) correct the blood volume; and (6) prevent infection. With these measures we have increased the survival rate.}, }
@article {pmid1126270, year = {1975}, author = {Nieves, PM and Valles, G and Arangúren, G and Maldonado, D}, title = {Gracilis muscle transplant for correction of traumatic anal incontinence: Report of a case.}, journal = {Diseases of the colon and rectum}, volume = {18}, number = {4}, pages = {349-354}, doi = {10.1007/BF02587400}, pmid = {1126270}, issn = {0012-3706}, mesh = {Adolescent ; Anal Canal/injuries/*surgery ; Anti-Bacterial Agents/therapeutic use ; Colostomy ; Electromyography ; Fecal Incontinence/etiology/*surgery ; Humans ; Ilium/surgery ; Male ; Muscles/*transplantation ; Postoperative Care ; Preoperative Care ; Sutures ; Thigh/surgery ; Transplantation, Autologous/methods ; }, abstract = {We report a case of traumatic anal incontinence successfully treated by the transplant of a gracilis muscle sling, using the technique described by Pickrell et al. in 1952. Although gracilis muscle transplant has been used in the treatment of congenital anal incontinence, its use in traumatic cases has not been widely accepted. Instead, many techniques offering uncertain results have been employed. We believe that Pickrell's technique is a worthwhile procedure in the presence of traumatic anal incontinence, particularly with noniatrogenic large perineal wounds, and that establishment of a temporary colostomy immediately after the injury, together with use of surgical steel sutures and antibiotics, is very helpful in averting posttransplant infection.}, }
@article {pmid1096182, year = {1975}, author = {Durham, NC}, title = {Construction of the perineal body in the female.}, journal = {Plastic and reconstructive surgery}, volume = {55}, number = {5}, pages = {529-532}, pmid = {1096182}, issn = {0032-1052}, mesh = {Adolescent ; Fecal Incontinence/surgery ; Female ; Humans ; Perineum/*abnormalities/surgery ; Postoperative Care ; Skin Transplantation ; *Surgery, Plastic ; Transplantation, Autologous/methods ; }, abstract = {A simple, one-stage operation is presented for the construction of a perineal body in a female who has a common rectovaginal opening, or cloaca. The operation has been performed on 3 teenaged girls, with an excellent result in each. In only one instance has been necessary to perform a secondary operation for correction of the rectal incontinence.}, }
@article {pmid1093511, year = {1975}, author = {Burrington, JD}, title = {Rectovaginal separation operation after a "cutback" procedure for anorectal anomalies.}, journal = {Archives of surgery (Chicago, Ill. : 1960)}, volume = {110}, number = {5}, pages = {471-475}, doi = {10.1001/archsurg.1975.01360110017004}, pmid = {1093511}, issn = {0004-0010}, mesh = {Adolescent ; Anal Canal/*abnormalities ; Child ; Colostomy ; Congenital Abnormalities/complications/surgery ; Female ; Humans ; Methods ; Postoperative Care ; Preoperative Care ; Rectum/*abnormalities/surgery ; Skin Transplantation ; Suture Techniques ; Transplantation, Autologous ; Urinary Tract Infections/etiology/prevention &amp; control ; Vagina/*surgery ; Wound Healing ; }, abstract = {The "cutback" procedure has been widely utilized over the 25 years for correction of mild forms of ectopic anus encountered in newborn females. As these children have become adolescents, some are troubled by the cosmetic appearance created by this procedure, recurrent urinary tract infections, and persistent vaginitis from continued fecal soiling. The rectovaginal separation procedure described (1) separates the rectum from the vagina by interposing adjacent tissues, (2) elongates the rectal canal, and (3) utilizes flaps of perineal skin to gain a normal degree of separation of the anus from the vagina. Five girls, ages 6 to 15 years, have undergone this procedure with a temporary loop colostomy to protect the perineum during healing. The long-term functional and cosmetic results three to seven years later have been excellent in four patients. The fifth girl has been observed only five months, but seems to have an excellent cosmetic result.}, }
@article {pmid1090980, year = {1975}, author = {Culp, WC}, title = {Releif of severe fecal impactions with water-soluble contrast enemas.}, journal = {Radiology}, volume = {115}, number = {1}, pages = {9-12}, doi = {10.1148/115.1.9}, pmid = {1090980}, issn = {0033-8419}, mesh = {Cecum/diagnostic imaging ; Child ; Child, Preschool ; Colon/diagnostic imaging ; Colon, Sigmoid/diagnostic imaging ; Diatrizoate/*therapeutic use ; *Enema ; Fecal Impaction/complications/diagnostic imaging/*therapy ; Female ; Humans ; Intestinal Obstruction/diagnostic imaging/etiology ; Kidney Transplantation ; Male ; Middle Aged ; Osmolar Concentration ; Radiography ; Solubility ; Transplantation, Homologous ; Water ; }, abstract = {High fecal impaction resulted in complete bowel obstruction in 2 children following renal transplantation and in one adult on chemotherapy and narcotics. The usual methods of relief failed, and water-soluble contrast enemas with a high osmolality were employed. Fluoroscopic control assured placement of the enema fluid at the site of obstruction, where it was very effective in relieving the impaction. It is suggested that such high-osmolality enemas be considered in patients with severe high fecal impactions before surgery is contemplated.}, }
@article {pmid1089443, year = {1975}, author = {Parsons, V and Choudhury, AA and Wass, JA and Vernon, A}, title = {Renal excretion of fluoride in renal failure and after renal transplantation.}, journal = {British medical journal}, volume = {1}, number = {5950}, pages = {128-130}, pmid = {1089443}, issn = {0007-1447}, mesh = {Calcium/metabolism ; Creatinine/metabolism ; Diet ; Feces/analysis ; Fluorides/blood/*metabolism/urine ; Humans ; Kidney Failure, Chronic/*metabolism ; *Kidney Transplantation ; Metabolic Clearance Rate ; Phosphates/metabolism ; Renal Dialysis ; Skin/metabolism ; }, abstract = {We have compared the renal excretion of fluoride in a variety of patients with chronic renal failure maintained with and without protein restriction before and during regular dialysis treatment and after transplantation. The patients tended to continue to excrete normal dietary loads of fluoride quite well until renal function was seriously reduced. From a regression of function on excretion the mean level of creatinine clearance when a normal dietary load of fluoride 0.0526 plus or minus 0.019 mmol/2 h (1.0 plus or minus 0.36 mg/24h) has a 90% chance of being excreted lies around 16 ml/min, a level when most patients with renal failure will be symptomatic. Acute loading of such patients with additional fluoride in the form of sodium fluoride from 40 mg to 60 mg/day showed a twofold to threefold increase of serum fluoride concentrations, slight increases in urinary fluoride excretion, and heavy tissue absorption, suggesting that prior fluoride loading of the skeleton had not taken place. These effects contrasted with those in one patient with normal renal function and with those in one patient with skeletal saturation due to prolonged loading. After renal transplantation fluoride excretion increased but reached normal levels within three months of satisfactory function, suggesting that fluoride loading in renal failure and during regular dialysis therapy had not been excessive.}, }
@article {pmid1214752, year = {1975}, author = {Arneri, V}, title = {[Incontinency alvi et urinae. Treatment by means of double transplantation of m. gracilis].}, journal = {Medicinski pregled}, volume = {28}, number = {11-12}, pages = {455-457}, pmid = {1214752}, issn = {0025-8105}, mesh = {Child ; Fecal Incontinence/*surgery ; Female ; Humans ; Muscles/*transplantation ; Transplantation, Autologous ; Urinary Incontinence/*surgery ; }, }
@article {pmid238688, year = {1975}, author = {Jutila, JW and Reed, ND and Isaak, DD}, title = {Studies on the immune response of congenitally athymic (nude) mice.}, journal = {Birth defects original article series}, volume = {11}, number = {1}, pages = {522-527}, pmid = {238688}, issn = {0547-6844}, mesh = {Animals ; *Antibody Formation ; Antigens ; Cats/immunology ; Cells, Cultured ; Chickens/immunology ; Erythrocytes/immunology ; Escherichia coli/immunology/isolation &amp; purification ; Feces/microbiology ; Hemolytic Plaque Technique ; *Immunity, Cellular ; Immunodiffusion ; Lipopolysaccharides ; Mice ; Mice, Inbred BALB C ; Mice, Nude/*immunology ; Polysaccharides, Bacterial ; Rats/immunology ; Sheep/immunology ; Skin Transplantation ; Spleen/cytology ; Streptococcus pneumoniae/immunology ; Thymus Gland/cytology/*immunology/transplantation ; Transplantation, Homologous ; }, abstract = {The central role of the thymus in immunity was assessed in nude mice. Nudes failed to reject allografts and xenografts and to respond to foreign erythrocytes but responded normally to endotoxin and pneumococcal polysaccharide. Thymus reconstitution was demonstrated in vivo and in vitro whereas reconstitution with thymic humoral factors or polyanions was not detected. Coliform overgrowth and depressed IgA levels in nudes appeared to contribute to wasting. These data emphasize the need for thymus participation in many immune phenomena.}, }
@article {pmid238684, year = {1975}, author = {Gelfand, EW and Parkman, R and Rosen, FS}, title = {Transplantation in severe combined immunodeficiency disease with hl-a identical bone marrow.}, journal = {Birth defects original article series}, volume = {11}, number = {1}, pages = {409-416}, pmid = {238684}, issn = {0547-6844}, mesh = {Animals ; Antibodies ; Antibody Formation ; Blood Group Incompatibility ; *Bone Marrow Cells ; *Bone Marrow Transplantation ; Candida/immunology ; Candidiasis, Oral/etiology ; Cell Separation ; Centrifugation, Density Gradient ; Diarrhea/etiology ; Feces/microbiology ; Female ; Goats/immunology ; Graft vs Host Reaction ; *Histocompatibility ; Humans ; Immunoelectrophoresis ; Immunoglobulin M/analysis ; Immunoglobulins/analysis ; Immunologic Deficiency Syndromes/*therapy ; Infant ; Karyotyping ; Lymphocyte Activation ; Salmonella typhimurium/isolation &amp; purification ; Skin Tests ; Spleen/pathology ; Thymus Gland/abnormalities ; }, abstract = {The immunologic reconstitution of 7 patients with severe combined immunodeficiency disease was attempted with bone marrow transplantation from histoidentical donors. Four patients were successfully reconstituted and discharged from the hospital. Two patients died with sepsis. One patient died from a preexisting neurologic disease. All the patients who have been successfully reconstituted have had some degree of graft-vs-host disease. A dose of 50 x 10(6) nucleated bone marrow cells per kg seems necessary for successful engraftment. The use of density gradient separation had no advantage over whole, unfractionated bone marrow.}, }
@article {pmid4612872, year = {1974}, author = {Bohmer, T}, title = {[Disturbances of calcium/phosphorus metabolism in chronic renal disease].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {94}, number = {33}, pages = {2320-2326}, pmid = {4612872}, issn = {0029-2001}, mesh = {Adult ; Calcium/blood/*metabolism/urine ; Chronic Disease ; Feces/analysis ; Female ; Humans ; Kidney Diseases/*metabolism ; Kidney Transplantation ; Male ; Middle Aged ; Nephritis/metabolism/surgery ; Phosphorus/blood/*metabolism ; Transplantation ; Vitamin D/metabolism ; }, }
@article {pmid4276478, year = {1974}, author = {Cheek, RC and Cole, FH and Smith, HF}, title = {Comparison of dacron and aortic autografts in wounds contaminated with fecal matter.}, journal = {The American surgeon}, volume = {40}, number = {8}, pages = {439-442}, pmid = {4276478}, issn = {0003-1348}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Aorta/*surgery ; Arteries/*transplantation ; Blood Vessel Prosthesis ; Dogs ; Feces ; Hemorrhage/etiology ; *Polyethylene Terephthalates ; Postoperative Complications ; Retroperitoneal Space ; Surgical Wound Infection/*prevention &amp; control ; Transplantation, Autologous ; }, }
@article {pmid4611675, year = {1974}, author = {Thompson, N}, title = {A review of autogenous skeletal muscle grafts and their clinical applications.}, journal = {Clinics in plastic surgery}, volume = {1}, number = {3}, pages = {349-403}, pmid = {4611675}, issn = {0094-1298}, mesh = {Adult ; Anal Canal/surgery ; Animals ; Cheek/surgery ; Child ; Cleft Lip/surgery ; Compartment Syndromes/surgery ; Eyelids/surgery ; Facial Paralysis/surgery ; Fecal Incontinence/surgery ; Female ; Foot/surgery ; Humans ; Male ; Mandibular Diseases/surgery ; Middle Aged ; Mouth/surgery ; Muscle Denervation ; Muscles/*transplantation ; Myofibrils/transplantation ; Ophthalmoplegia/surgery ; Palate/surgery ; Paralysis/surgery ; Pharyngeal Diseases/surgery ; *Surgery, Plastic ; Thumb/surgery ; Transplantation, Autologous ; Urinary Incontinence/surgery ; }, }
@article {pmid4830797, year = {1974}, author = {Chomchai, C and Bhadrachari, N and Nigro, ND}, title = {The effect of bile on the induction of experimental intestinal tumors in rats.}, journal = {Diseases of the colon and rectum}, volume = {17}, number = {3}, pages = {310-312}, doi = {10.1007/BF02586971}, pmid = {4830797}, issn = {0012-3706}, mesh = {Adenocarcinoma/*etiology ; Animals ; *Azo Compounds ; *Bile ; Bile Acids and Salts/analysis ; Colonic Neoplasms/etiology ; Common Bile Duct/transplantation ; Feces/analysis ; Injections, Subcutaneous ; Intestinal Neoplasms/*etiology ; *Intestine, Small ; Male ; Methane ; Neoplasms, Experimental/etiology ; Nitrogen Oxides ; Polyps/*etiology ; Rats ; Transplantation, Autologous ; }, }
@article {pmid4596206, year = {1974}, author = {Berger, M and Schuessler, JS and Carajal, HF and Lorentz, WB and Travis, LB and Tyson, KR}, title = {Obturator intestinal obstruction following renal allotransplantation: relief with hyperosmolar enemas.}, journal = {Surgery}, volume = {75}, number = {5}, pages = {746-749}, pmid = {4596206}, issn = {0039-6060}, mesh = {Adolescent ; Child ; Child, Preschool ; Colonic Diseases/complications/diagnostic imaging ; Diarrhea/chemically induced ; Diatrizoate ; *Enema ; Fecal Impaction/complications ; Female ; Humans ; Intestinal Obstruction/diagnostic imaging/*etiology/therapy ; *Kidney Transplantation ; Male ; Osmolar Concentration ; *Postoperative Complications ; Radiography, Abdominal ; Transplantation, Homologous ; }, }
@article {pmid4545212, year = {1974}, author = {Stanley-Brown, EG}, title = {Massive hemorrhage after colon interposition: early and late.}, journal = {Journal of pediatric surgery}, volume = {9}, number = {2}, pages = {235-237}, doi = {10.1016/s0022-3468(74)80129-6}, pmid = {4545212}, issn = {0022-3468}, mesh = {Blood Transfusion ; Child, Preschool ; Colon/*transplantation ; Esophageal Atresia/surgery ; Esophageal Diseases/surgery ; Esophagus/*surgery ; Female ; Gastrointestinal Hemorrhage/*etiology/therapy ; Hematemesis/etiology ; Humans ; Infant ; Male ; Melena/etiology ; Peptic Ulcer/*complications ; Surgical Wound Infection/etiology ; Time Factors ; Transplantation, Autologous ; }, }
@article {pmid4151810, year = {1974}, author = {Lopez, C and Biggar, WD and Park, BH and Good, RA}, title = {Nonparalytic poliovirus infections in patients with severe combined immunodeficiency disease.}, journal = {The Journal of pediatrics}, volume = {84}, number = {4}, pages = {497-502}, doi = {10.1016/s0022-3476(74)80667-0}, pmid = {4151810}, issn = {0022-3476}, mesh = {Bone Marrow Cells ; Bone Marrow Transplantation ; Feces/microbiology ; Female ; Graft vs Host Reaction ; Humans ; Immunity, Cellular ; Immunologic Deficiency Syndromes/diagnosis/*etiology/immunology ; Lymphocytes/immunology ; Male ; Poliomyelitis/etiology/*immunology ; Poliovirus/isolation &amp; purification ; Poliovirus Vaccine, Oral/*adverse effects ; }, }
@article {pmid4360465, year = {1974}, author = {Lopez, C and Simmons, RL and Mauer, SM and Najarian, JS and Good, RA and Gentry, S}, title = {Association of renal allograft rejection with virus infections.}, journal = {The American journal of medicine}, volume = {56}, number = {3}, pages = {280-289}, doi = {10.1016/0002-9343(74)90609-3}, pmid = {4360465}, issn = {0002-9343}, mesh = {Biopsy ; Complement Fixation Tests ; Creatinine/blood ; Cytomegalovirus/isolation &amp; purification ; Feces/microbiology ; Fever/etiology ; *Graft Rejection ; Herpes Simplex/complications ; Herpes Zoster/complications/microbiology ; Herpesviridae Infections/complications/microbiology ; Humans ; Immunosuppression Therapy ; Kidney/pathology ; *Kidney Transplantation ; Leukopenia/etiology ; Neutralization Tests ; Simplexvirus/isolation &amp; purification ; Transplantation, Homologous ; Urine/microbiology ; Virus Diseases/*complications ; }, }
@article {pmid4840819, year = {1974}, author = {Zawirska, B and Grzebieluch, M}, title = {Disorders of porphyrin metabolism induced with 2-allyloxy-3-methylbenzamide in healthy rats and rats bearing transplantable Yoshida sarcoma.}, journal = {Archivum immunologiae et therapiae experimentalis}, volume = {22}, number = {2}, pages = {237-249}, pmid = {4840819}, issn = {0004-069X}, mesh = {Allyl Compounds/*pharmacology ; Animals ; Benzamides/*pharmacology ; Bone Marrow/analysis ; Feces/analysis ; Female ; Fluoroscopy ; Kidney/analysis ; Liver/analysis ; Male ; Neoplasm Transplantation ; Porphyrias/chemically induced ; Porphyrins/analysis/*metabolism/urine ; Rats ; Rats, Inbred Strains ; Sarcoma, Yoshida/*metabolism ; }, }
@article {pmid4199579, year = {1973}, author = {Bodey, GP}, title = {Patient isolation units for cancer patients treated with chemical immunosuppressive agents.}, journal = {Transplantation proceedings}, volume = {5}, number = {3}, pages = {1279-1284}, pmid = {4199579}, issn = {0041-1345}, mesh = {Acute Disease ; Air Microbiology ; Anti-Bacterial Agents/therapeutic use ; Feces/microbiology ; Immunosuppressive Agents/therapeutic use ; Infection Control ; Leukemia/drug therapy/*therapy ; Leukocyte Count ; *Patient Isolators ; Pharynx/microbiology ; Water Microbiology ; }, }
@article {pmid4275344, year = {1973}, author = {Coburn, JW and Hartenbower, DL and Massry, SG}, title = {Intestinal absorption of calcium and the effect of renal insufficiency.}, journal = {Kidney international}, volume = {4}, number = {2}, pages = {96-104}, doi = {10.1038/ki.1973.88}, pmid = {4275344}, issn = {0085-2538}, mesh = {Adenosine Triphosphatases/metabolism ; Alkaline Phosphatase/metabolism ; Biological Transport, Active ; Calcium/analysis/*metabolism/therapeutic use ; Calcium Radioisotopes ; Calcium, Dietary/metabolism ; Chronic Kidney Disease-Mineral and Bone Disorder/drug therapy ; Diffusion ; Dihydroxycholecalciferols/metabolism ; Feces/analysis ; Homeostasis ; Humans ; *Intestinal Absorption ; Intestinal Mucosa/physiology ; Intestine, Small/physiopathology ; Kidney Transplantation ; Parathyroid Glands/physiology ; Prednisone/pharmacology ; Protein Binding ; Renal Dialysis ; Transplantation, Homologous ; Uremia/*metabolism ; Vitamin D/physiology ; }, }
@article {pmid4578366, year = {1973}, author = {Bernstein, WC and Nivatvongs, S and Tallent, MB}, title = {Colonic and rectal complications of kidney transplantation in man.}, journal = {Diseases of the colon and rectum}, volume = {16}, number = {4}, pages = {255-263}, doi = {10.1007/BF02587698}, pmid = {4578366}, issn = {0012-3706}, mesh = {Adolescent ; Adult ; Child ; Colitis, Ulcerative/etiology/physiopathology ; Colonic Diseases/*etiology ; Fecal Impaction/etiology ; Gastrointestinal Hemorrhage/complications ; Graft Rejection ; Humans ; Immunosuppressive Agents/adverse effects ; Infections/etiology ; Intestinal Perforation/etiology ; *Kidney Transplantation ; Necrosis ; Pain/complications ; *Postoperative Complications ; Rectal Diseases/*etiology ; Rectum ; Transplantation, Homologous ; Ureteral Obstruction/complications ; }, }
@article {pmid4706866, year = {1973}, author = {Schwemmle, K and Hunger, J}, title = {[Anorectal prolapse].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {98}, number = {22}, pages = {1125-1129}, doi = {10.1055/s-0028-1106979}, pmid = {4706866}, issn = {0012-0472}, mesh = {Anus Diseases/*surgery ; Child ; Dura Mater/transplantation ; Fecal Incontinence/etiology ; Freeze Drying ; Humans ; Methods ; Rectal Prolapse/complications/etiology/*surgery ; Sacrum/surgery ; Transplantation, Homologous ; }, }
@article {pmid4807571, year = {1973}, author = {Mallinson, CN and Drasar, BS and Trounce, JR}, title = {Fat malabsorption associated with bacterial colonization of a colon transplant: a case report.}, journal = {Guy's Hospital reports}, volume = {122}, number = {3-4}, pages = {231-243}, pmid = {4807571}, issn = {0017-5889}, mesh = {Amino Acids/blood ; Ampicillin/therapeutic use ; Bacteria/isolation &amp; purification ; Bacterial Infections/*complications ; Barium Sulfate ; Body Weight ; Celiac Disease/drug therapy/etiology ; Chloramphenicol/therapeutic use ; Colon/analysis/diagnostic imaging/microbiology/*transplantation ; *Dietary Fats ; Esophagoscopy ; Fats/analysis ; Feces/analysis ; Female ; Gastroesophageal Reflux/*surgery ; Humans ; Lipids/analysis ; Malabsorption Syndromes/*etiology ; Manometry ; Middle Aged ; Postoperative Complications/*etiology ; Radiography ; Tetracycline/therapeutic use ; Transplantation, Autologous ; Vomiting/etiology ; }, }
@article {pmid4802618, year = {1973}, author = {Giordano, C and Esposito, R and Pluvio, M}, title = {The effects of oxidised starch on blood and faecal nitrogen in uraemia.}, journal = {Proceedings of the European Dialysis and Transplant Association. European Dialysis and Transplant Association}, volume = {10}, number = {0}, pages = {136-142}, pmid = {4802618}, issn = {0071-2736}, mesh = {Adult ; Ammonia/blood ; Blood Urea Nitrogen ; Child ; Feces/*analysis ; Female ; Humans ; Male ; Middle Aged ; Nitrogen/*blood/metabolism ; Starch/administration &amp; dosage/*therapeutic use ; Uremia/diet therapy/*drug therapy/metabolism ; }, }
@article {pmid4802503, year = {1973}, author = {Man, NK and Drueke, T and Paris, J and Monteverde, CE and Nucete, MR and Zingraff, J and Jungers, P}, title = {Increased nitrogen removal from the intestinal tract of uraemic patients.}, journal = {Proceedings of the European Dialysis and Transplant Association. European Dialysis and Transplant Association}, volume = {10}, number = {0}, pages = {143-151}, pmid = {4802503}, issn = {0071-2736}, mesh = {Adolescent ; Adult ; Aged ; Ammonia/metabolism ; Blood Urea Nitrogen ; Dietary Proteins/administration &amp; dosage ; Feces/analysis ; Humans ; Hydrogen-Ion Concentration ; Intestinal Mucosa/*metabolism ; Lactulose/administration &amp; dosage/therapeutic use ; Middle Aged ; Nitrogen/*metabolism ; Starch/metabolism/therapeutic use ; Uremia/diet therapy/drug therapy/*metabolism ; }, }
@article {pmid4587502, year = {1973}, author = {Vossen, JM and de Koning, J and van Bekkum, DW and Dicke, KA and Eysvoogel, VP and Hijmans, W and van Loghem, E and Rádl, J and van Rood, JJ and van der Waay, D and Dooren, LJ}, title = {Successful treatment of an infant with severe combined immunodeficiency by transplantation of bone marrow cells from an uncle.}, journal = {Clinical and experimental immunology}, volume = {13}, number = {1}, pages = {9-20}, pmid = {4587502}, issn = {0009-9104}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Bone Marrow Cells ; *Bone Marrow Transplantation ; Centrifugation, Density Gradient ; Feces/microbiology ; Genotype ; Histocompatibility Antigens ; Histocompatibility Testing ; Humans ; Immunoglobulin G/analysis ; Immunologic Deficiency Syndromes/genetics/nursing/*therapy ; Infant ; Isoantigens/analysis ; Lymphocyte Activation ; Male ; Patient Isolators ; Pedigree ; Pharynx/microbiology ; Skin/microbiology ; Tissue Donors ; Transplantation, Homologous ; }, abstract = {A 4½-month-old boy suffering from congenital severe combined immunodeficiency was successfully treated by transplantation of bone marrow-derived cells. His parents were cousins in the first degree. The donor was a 32-year-old maternal uncle, who was HL-A genotypically identical with the patient as was shown by serological typing and MLC. A stem cell rich fraction of the donor's bone marrow was prepared by albumin gradient centrifugation. The infant showed a full immunological reconstitution without any sign of GVH disease. Remarkably the only allotypic marker of his IgG which was different from the donor allotype remained in the serum after transplantation, and even showed an increase of its level. The infant was nursed in strict reverse isolation and his unfavourable endogenous microflora of high potential pathogenicity was eliminated by antibiotic decontamination.}, }
@article {pmid4585260, year = {1973}, author = {Serebriakov, NG and Suskova, VS and Petrosova, VN and Emets, VI and Skriabina, EG}, title = {[Pharmacodynamics of antilymphocyte globulin (ALG) in mice with skin allotransplants. I. Distribution and elimination of ALG-I-131 during single and multiple administration].}, journal = {Vestnik Akademii meditsinskikh nauk SSSR}, volume = {28}, number = {8}, pages = {77-81}, pmid = {4585260}, issn = {0002-3027}, mesh = {Animals ; Antibodies ; Antilymphocyte Serum/*administration &amp; dosage/urine ; Feces/metabolism ; Injections, Intraperitoneal ; Iodine Radioisotopes ; Kidney/metabolism ; Liver/metabolism ; Lung/metabolism ; Lymph Nodes/metabolism ; Male ; Mice ; Mice, Inbred CBA ; *Skin Transplantation ; Spleen/metabolism ; Thymus Gland/metabolism ; Transplantation, Homologous ; }, }
@article {pmid4196652, year = {1973}, author = {Smith, RF and Dayton, SL}, title = {Colonization of burns by Streptococcus faecalis related to contaminated porcine xenografts.}, journal = {Texas reports on biology and medicine}, volume = {31}, number = {1}, pages = {47-54}, pmid = {4196652}, issn = {0040-4675}, mesh = {Acute Disease ; Adolescent ; Animals ; Bacteriuria ; Burns/*microbiology/therapy ; Child ; Child, Preschool ; Enterococcus faecalis/*isolation &amp; purification ; Feces/microbiology ; Female ; Humans ; Infant ; Male ; Microbial Sensitivity Tests ; Sepsis ; Skin/microbiology ; Skin Transplantation ; Staphylococcus/isolation &amp; purification ; Swine ; Time Factors ; *Transplantation, Heterologous ; }, }
@article {pmid4655860, year = {1972}, author = {Holt, RJ and Newman, RL}, title = {Laboratory assessment of the antimycotic drug clotrimazole.}, journal = {Journal of clinical pathology}, volume = {25}, number = {12}, pages = {1089-1097}, pmid = {4655860}, issn = {0021-9746}, mesh = {Antifungal Agents/blood/*pharmacology/therapeutic use/urine ; Aspergillus/drug effects ; Benzene Derivatives/pharmacology ; Candida/drug effects ; Candidiasis/drug therapy ; Cryptococcus/drug effects ; Humans ; Imidazoles/blood/*pharmacology/therapeutic use/urine ; Infant ; Microbial Sensitivity Tests ; Mutation ; }, abstract = {Laboratory studies on clotrimazole showed that it had marked activity in vitro against all the Candida spp. and Cryptococcus spp. tested, against almost all strains of dermatophytes, and against Aspergillus spp and other fungal genera responsible for systemic mycoses; it had limited activity towards Gram-positive bacteria. The majority of Candida strains required MICs below 1 mug/ml and MCCs below 2 mug/ml.Serum, urine, and faecal assays of clotrimazole were made by microbiological methods on five children who received 100 mg/kg/day clotrimazole for several weeks. In-vitro sensitivity tests and biological fluid drug assays are also reported on specimens from 18 patients in other hospitals receiving clotrimazole for severe candidosis; several were renal transplant cases. Similar investigations are reported on specimens from 18 patients with pulmonary aspergilloses. The significance of low levels of the drug in body fluids, even after prolonged therapy, is discussed, and it is suggested that clotrimazole may be the first of a long series of imidazole derivatives with varying pharmacological and therapeutic properties.}, }
@article {pmid4567310, year = {1972}, author = {van der Waaij, D and Speltie, TM and Vossen, JM}, title = {Biotyping of Enterobacteriaceae as a test for the evaluation of isolation systems.}, journal = {The Journal of hygiene}, volume = {70}, number = {4}, pages = {639-650}, pmid = {4567310}, issn = {0022-1724}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacteriological Techniques ; Cross Infection/prevention &amp; control ; Enterobacteriaceae/*classification/isolation &amp; purification ; Feces/microbiology ; Fermentation ; Humans ; Kidney Transplantation ; Leukemia, Myeloid, Acute/microbiology ; *Patient Isolators ; }, abstract = {Arguments in favour of biotyping of Enterobacteriaceae excreted in the faeces of isolated patients, as a method of investigating the efficiency of the isolation procedures, are presented as well as a technical outline of the procedure. The study included three kidney transplantation patients, five acute myeloid leukaemia patients and four healthy persons as controls.The results show, apart from new colonizations during isolation, a difference in the mean number of contaminations and colonizations with different Enterobacteriaceae biotypes. It is concluded from these results, that the isolation procedures were not completely effective and that the AML patients studied had a decreased colonization resistance of their digestive tract. This was less evident in the kidney transplant group.}, }
@article {pmid5050633, year = {1972}, author = {Lewis, MI}, title = {Gracilis-muscle transplant for the correction of anal incontinence: report of a case.}, journal = {Diseases of the colon and rectum}, volume = {15}, number = {4}, pages = {292-298}, doi = {10.1007/BF02589889}, pmid = {5050633}, issn = {0012-3706}, mesh = {Adolescent ; Anal Canal/innervation/*surgery ; Diet Therapy ; Fecal Incontinence/*surgery ; Humans ; Male ; Muscles/anatomy &amp; histology/*transplantation ; Postoperative Care ; Preoperative Care ; Thigh ; }, }
@article {pmid4630613, year = {1972}, author = {Vossen, JM and van der Waay, D}, title = {Reverse isolation in bone marrow transplantation: ultra-clean room compared with laminar flow technique. II. Microbiological and clinical results.}, journal = {Revue europeenne d'etudes cliniques et biologiques. European journal of clinical and biological research}, volume = {17}, number = {6}, pages = {564-574}, pmid = {4630613}, issn = {0035-3019}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Aspergillus/isolation &amp; purification ; Bacillus/isolation &amp; purification ; *Bone Marrow Cells ; *Bone Marrow Transplantation ; Candida/isolation &amp; purification ; Child ; Enterobacteriaceae/isolation &amp; purification ; Feces/microbiology ; Female ; Humans ; Immunosuppression Therapy ; Infant ; Infection Control ; Infections/*microbiology ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Nasopharynx/microbiology ; *Patient Isolators ; Pseudomonas/isolation &amp; purification ; Skin/microbiology ; Staphylococcus/isolation &amp; purification ; }, }
@article {pmid5026852, year = {1972}, author = {Kelly, JD and Dineen, JK}, title = {The suppression of rejection of Nippostrongylus brasiliensis in the rat by promethazine hydrochloride. The site of immunological impairment.}, journal = {Immunology}, volume = {22}, number = {3}, pages = {361-370}, pmid = {5026852}, issn = {0019-2805}, mesh = {Animals ; Antigens ; Biogenic Amines/metabolism ; Feces ; Hookworm Infections/*immunology ; Immune Sera ; Immunity/*drug effects ; Immunization ; Injections, Intravenous ; Intestine, Small ; Lymph Nodes/cytology ; Lymphocyte Transfusion ; Lymphocytes/*drug effects ; Male ; Parasite Egg Count ; Promethazine/*pharmacology ; Rats ; Transplantation, Homologous ; }, abstract = {Rats were treated parenterally with promethazine hydrochloride during a primary infection with Nippostrongylus brasiliensis. Survival of the parasites in the small intestine was prolonged and this suggested that promethazine inhibited rejection of the parasites. The site of immunological impairment in promethazine-treated animals was investigated by transfer of resistance to the parasite with immune lymphocytes. As previous studies have shown that the mechanism of rejection of helminths is diphasic, comprising specific lymphocyte—antigen reaction and involvement of myeloid cells and release of biogenic amines, it is conceptually possible that promethazine may act at either level. The functional activity of immune mesenteric lymph node cells, as assessed by their capacity to cause parasite rejection, was reduced by treatment of cell recipients with promethazine. In addition, lymphocytes from donors treated with promethazine during immunization were also markedly less effective than cells from untreated donors when transferred to syngeneic recipients. These results show that the in vivo effect of promethazine may be mediated at the specific lymphoid level as well as at the myeloid-amine level. Direct confirmation of this finding was obtained showing that serum from promethazine-treated rats seriously impaired the activity of immune lymphocytes in cellular transfer of resistance to N. brasiliensis. In this study immune lymphocytes were incubated at 37° for 1 hour with serum from promethazine-treated uninfected rats and then washed immediately before transfer to syngeneic recipients.}, }
@article {pmid4557831, year = {1972}, author = {Colin, R}, title = {[Anal incontinence and rectal prolapse due to spina bifida. Cure by Oor-Loygue rectopexy and Pickrell's myoplasty].}, journal = {Chirurgie; memoires de l'Academie de chirurgie}, volume = {98}, number = {2}, pages = {113-117}, pmid = {4557831}, issn = {0001-4001}, mesh = {Adult ; Fecal Incontinence/etiology/*surgery ; Humans ; Male ; Methods ; Muscles/transplantation ; Rectal Prolapse/etiology/*surgery ; Spinal Dysraphism/*complications ; Transplantation, Autologous ; }, }
@article {pmid5062015, year = {1972}, author = {Kelly, JD and Dineen, JK}, title = {The cellular transfer to immunity to Nippostrongylus brasiliensis in inbred rats (Lewis strain).}, journal = {Immunology}, volume = {22}, number = {2}, pages = {199-210}, pmid = {5062015}, issn = {0019-2805}, mesh = {Ancylostomatoidea/anatomy &amp; histology ; Animals ; Feces ; Hookworm Infections/*immunology ; *Immunity, Cellular ; Immunization ; Immunization, Passive ; Lymph Nodes/transplantation ; Parasite Egg Count ; Rats ; Rats, Inbred Strains/*immunology ; Time Factors ; Transplantation, Homologous ; }, abstract = {Mesenteric lymph node cells obtained from highly inbred donor rats (Lewis strain), resistant to Nippostrongylus brasiliensis infection, were syngeneically transferred by intravenous injection into previously uninfected recipients. The adoptively immunized recipients were then challenged with either 1500 or 3000 third stage N. brasiliensis larvae on the day of cell transfer. The degree of resistance transferred was assessed by monitoring daily faecal egg output, differential worm burdens on days 6 and 10 of infection and the number of eggs per uterus in gravid worms. The syngeneic transfer of 100 × 10[6] immune mesenteric lymph node cells invariably resulted in suppression of egg production, a two- to four-fold reduction in the number of eggs per uterus in gravid females and rejection of at least 75 per cent of adult worms by days 6 and 10 of infection. It was also noted that mesenteric lymph node cells obtained from donors on day 15 of a primary infection were more effective than those obtained from donors immunized by multiple infections. Immune cells transferred from donors on day 4 of infection were equally effective with those transferred on day 0. However, immune cells transferred on or after day 10 of infection had little or no effect and this shows that the parasite is less susceptible to an attack mounted by the transferred cells during the later stages of infection.}, }
@article {pmid4551886, year = {1972}, author = {Ruiz, JO and Uchida, H and Schultz, LS and Lillehei, RC}, title = {Function studies after auto- and allotransplantation and denervation of pancreaticoduodenal segments in dogs.}, journal = {American journal of surgery}, volume = {123}, number = {2}, pages = {236-242}, doi = {10.1016/0002-9610(72)90338-8}, pmid = {4551886}, issn = {0002-9610}, mesh = {Amylases/blood ; Animals ; Blood Glucose ; Dogs ; Drainage ; Duodenum/innervation/*transplantation ; Feces/analysis ; Hematocrit ; Insulin/*metabolism ; Insulin Secretion ; Leukocyte Count ; Lipids/analysis ; Pancreas/cytology/innervation ; *Pancreas Transplantation ; Tolbutamide/pharmacology ; Transplantation Immunology ; Transplantation, Autologous ; Transplantation, Homologous ; Xylose/metabolism ; }, }
@article {pmid5062546, year = {1972}, author = {Dineen, JK and Kelly, JD}, title = {The suppression of rejection of Nippostrongylus brasiliensis in lactating rats: the nature of the immunological defect.}, journal = {Immunology}, volume = {22}, number = {1}, pages = {1-12}, pmid = {5062546}, issn = {0019-2805}, mesh = {Animals ; Feces ; Female ; Fertility ; Hookworm Infections/*immunology ; *Immunity ; *Lactation ; Larva ; Lymph Nodes/immunology/transplantation ; Parasite Egg Count ; Pregnancy ; Rats ; Transplantation, Homologous ; }, abstract = {Lactating female rats infected with 3000 third-stage larvae of Nippostrongylus brasiliensis showed significant increases in worm fecundity and total worm burdens when compared with infected nulliparous controls. Statistically significant differences were recorded for each of the three periods of infection, although these differences were of greatest magnitude during Period 3 (16–30 days of infection). Immune mesenteric lymph node cells (100 × 10[6]), obtained from nulliparous female donors on Day 15 of a primary infection, were transferred syngeneically to lactating female recipients. The transferred cells invariably caused suppression of worm fecundity, reduction in the number of eggs per uterus in gravid female worms and rejection of a substantial proportion of worms by Day 10 of a challenge infection in the lactating recipients. The results of this study showed that immune cells were functional in lactating female recipients and that transfer of immune cells repaired the deficit in the rejection mechanism. Mesenteric lymph node cells (100 × 10[6]), obtained from lactating female donors on Day 15 of a primary infection, were transferred syngeneically to nulliparous female recipients. The transferred cells caused suppression of worm fecundity, reduction in the number of eggs per uterus in gravid female worms and rejection of the majority of parasites by Day 10 of a challenge infection in the nulliparous recipients. Clearly, potentially immune lymphoid cells were present in the mesenteric nodes of lactating females at the time that the rejection mechanism was severely impaired. Mesenteric lymph node cells obtained from infected lactating donors were substantially less effective in lactating recipients than in nulliparous recipients. These cells caused the expulsion of 51 per cent of worms by Day 10 in lactating recipients, whereas they caused expulsion of 99 per cent of worms in nulliparous recipients. These observations suggest that the inductive processes of the immune response occur normally, but that differentiation of induced cells to effector cells is impaired in lactating animals.}, }
@article {pmid4399728, year = {1971}, author = {Rothwell, TL and Dineen, JK and Love, RJ}, title = {The role of pharmacologically-active amines in resistance to Trichostrongylus colubriformis in the guinea-pig.}, journal = {Immunology}, volume = {21}, number = {6}, pages = {925-938}, pmid = {4399728}, issn = {0019-2805}, mesh = {5-Hydroxytryptophan/pharmacology ; Animals ; Basophils/immunology ; Eosinophils/immunology ; Feces/microbiology ; Guinea Pigs ; Histamine/pharmacology/*physiology ; Histamine H1 Antagonists/pharmacology ; Histidine/pharmacology ; Hydrazines/pharmacology ; *Immunity/drug effects ; Immunization ; Lymph Nodes/transplantation ; Lymphocytes/immunology ; Methyldopa/pharmacology ; Methysergide/pharmacology ; Parasite Egg Count ; Promethazine/pharmacology ; Pyrroles/pharmacology ; Reserpine/pharmacology ; Serotonin/pharmacology/*physiology ; Transplantation, Homologous ; Trichostrongyloidiasis/*immunology ; Tryptophan/pharmacology ; }, abstract = {The role of histamine and 5-hydroxytryptamine in resistance to Trichostrongylus colubriformis in the guinea-pig has been investigated by studying the effect of amine antagonists (promethazine, mepyramine and methysergide), inhibitors of amine synthesis (α-hydrazino analogue of histidine and α-methyl dopa), depletion of tissue stores of the amines with reserpine and by attempts to elevate levels of the amines by oral administration of the amines and their immediate metabolic precursors (L-histidine, L-tryptophan and 5-hydroxy-DL-tryptophan). The results show that promethazine suppressed the development of resistance during a primary infection and inhibited expulsion of the parasite in actively and adoptively immunized animals. Mepyramine and the α-hydrazino analogue of histidine inhibited expulsion of the parasite in actively immunized guinea-pigs although methysergide and α-methyl dopa were not effective. Reserpine suppressed rejection of a challenge infection in actively and adoptively immunized animals, and oral administration of the histamine precursor (L-histidine) and 5-hydroxytryptamine increased the resistance which develops during a primary infection. These results show that histamine and 5-hydroxytryptamine play roles in the mechanism of resistance to T. colubriformis in the guinea-pig. It is suggested that the mechanism of resistance to the helminth is biphasic. The first phase is immunologically specific and probably involves interaction between antigens and sensitized lymphocytes, which acts as a trigger for myeloid (eosinophil and basophil) involvement and the release of pharmacologically active amines. The second phase, which is non-specific, appears to be the final effector mechanism, and involves the rejection of the parasites either directly or indirectly by the action of the amines.}, }
@article {pmid4330458, year = {1971}, author = {Benveniste, J and Lespinats, G and Adam, C and Salomon, JC}, title = {Immunoglobulins in intact, immunized, and contaminated axenic mice: study of serum IgA.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {107}, number = {6}, pages = {1647-1655}, pmid = {4330458}, issn = {0022-1767}, mesh = {Absorption ; Animals ; *Antibody Formation ; Antibody Specificity ; Antigens ; Antigens, Bacterial ; Corynebacterium/immunology ; Digestive System/microbiology ; Feces/immunology ; *Germ-Free Life ; *Immunization ; Immunodiffusion ; Immunoglobulin A/analysis ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins/*analysis ; Mice ; Mice, Inbred Strains ; Myeloma Proteins ; Neoplasm Transplantation ; Neoplasms, Experimental ; Poliovirus ; Prednisolone/pharmacology ; Salmonella typhi/immunology ; }, }
@article {pmid5113269, year = {1971}, author = {Gizycka, I and Romanowska, A}, title = {[Results of gracilis muscle transposition in the treatment of fecal incontinence in children].}, journal = {Polski tygodnik lekarski (Warsaw, Poland : 1960)}, volume = {26}, number = {36}, pages = {1393-1395}, pmid = {5113269}, issn = {0032-3756}, mesh = {Adolescent ; Child ; Fecal Incontinence/*surgery ; Humans ; Leg ; Muscles/*transplantation ; Posture ; Transplantation, Autologous ; }, }
@article {pmid4932581, year = {1971}, author = {Pollock, WJ and Litwin, MS}, title = {Hemianoplasty.}, journal = {Plastic and reconstructive surgery}, volume = {47}, number = {6}, pages = {568-571}, doi = {10.1097/00006534-197106000-00009}, pmid = {4932581}, issn = {0032-1052}, mesh = {Accidents, Traffic ; Adolescent ; Amputation, Surgical ; Anal Canal/injuries/*surgery ; Defecation ; Fecal Incontinence/etiology/*surgery ; Follow-Up Studies ; Humans ; Leg Injuries ; Male ; Methods ; Rectum/injuries ; *Skin Transplantation ; Suture Techniques ; Transplantation, Autologous ; }, }
@article {pmid5572928, year = {1971}, author = {Kaplan, I and Alfandary, H}, title = {The surgical treatment of rectal incontinence by gracilis muscle transplant.}, journal = {American journal of proctology}, volume = {22}, number = {2}, pages = {102-104}, pmid = {5572928}, issn = {0002-9521}, mesh = {Child ; Fecal Incontinence/*surgery ; Female ; Humans ; Muscles/*surgery ; Thigh/surgery ; }, }
@article {pmid4927401, year = {1971}, author = {Solberg, CO and Matsen, JM and Vesley, D and Wheeler, DJ and Good, RA and Meuwissen, HJ}, title = {Laminar airflow protection in bone marrow transplantation.}, journal = {Applied microbiology}, volume = {21}, number = {2}, pages = {209-216}, pmid = {4927401}, issn = {0003-6919}, mesh = {*Air Microbiology ; Bacteria/classification/*isolation &amp; purification ; Bacteriological Techniques ; Bacteriophage Typing ; *Bone Marrow Transplantation ; Cross Infection/prevention &amp; control ; Equipment and Supplies, Hospital ; Feces/microbiology ; Humans ; Immunologic Deficiency Syndromes/*therapy ; Infant ; *Intensive Care Units ; Lymphopenia/*microbiology/therapy ; Male ; Methods ; Nose/microbiology ; Perineum/microbiology ; Personnel, Hospital ; Pharynx/microbiology ; Serotyping ; Statistics as Topic ; Transplantation, Homologous ; *Ventilation ; }, abstract = {A laminar airflow room was used to provide a low-pathogen environment for a child with lymphopenic immune deficiency transplanted with paternal bone marrow. Comparison of flora from the patient, personnel, and the environment indicated that no colonization with exogenous organisms occurred in the patient during the 45-day period of study. The number of organisms recovered from the laminar airflow room was exceedingly small. Conventional hospital isolation rooms contained more bacteria and fungi than the laminar airflow room, even when strict aseptic procedures were followed in the former. Patients with lymphopenic immune deficiency and agranulocytosis admitted to conventional isolation rooms were colonized with exogenous organisms within 1 week. Each developed infection with these strains, and one patient died. Laminar airflow isolation seems at present the best means to prevent exogenous infection during hospitalization of patients with lymphopenic and other severe immune-deficiency diseases and may be essential when bone marrow transplantation is performed to treat their immunological defect.}, }
@article {pmid4395326, year = {1971}, author = {Solberg, CO and Meuwissen, HJ and Needham, RN and Good, RA and Matsen, JM}, title = {Infectious complications in bone marrow transplant patients.}, journal = {British medical journal}, volume = {1}, number = {5739}, pages = {18-23}, pmid = {4395326}, issn = {0007-1447}, mesh = {Adolescent ; Adult ; Antilymphocyte Serum/adverse effects ; Blood/microbiology ; *Bone Marrow Transplantation ; Candidiasis/epidemiology/etiology ; Child ; Cross Infection ; Drug Resistance, Microbial ; Feces/microbiology ; Female ; Graft vs Host Reaction ; Haemophilus Infections/epidemiology ; Humans ; Immunosuppressive Agents/adverse effects ; Infant ; Infections/*etiology ; Klebsiella Infections/epidemiology ; Male ; Patient Isolators ; Pneumonia, Pneumocystis/etiology ; *Postoperative Complications ; Sepsis/epidemiology/etiology/microbiology ; Staphylococcal Infections/epidemiology ; Transplantation, Homologous ; }, abstract = {In 11 patients receiving transplants of allogeneic bone marrow, the graft was successful in six. Nine patients developed infections, and six died-five of septicaemia and one of Pneumocystis carinii pneumonia. Fifty individual infections occurred. Predisposing factors included severe underlying diseases, long-term exposure to resistant hospital organisms, heavy immunosuppressive therapy, and graft-versus-host disease. Gram-negative bacilli and Candida albicans were the most common causative organisms. In every instance of septicaemia identical organisms were isolated from blood cultures and simultaneously obtained stool cultures. Infection with exogenous organisms often occurred in patients occupying conventional isolation rooms. Isolation of one patient for 45 days in a laminar air flow room prevented infection with exogenous organisms.}, }
@article {pmid5562849, year = {1971}, author = {Le Mer,  and Paintaud, }, title = {[Cure of anal incontinence by the myoplasty of Pickrell-Richard].}, journal = {Chirurgie; memoires de l'Academie de chirurgie}, volume = {97}, number = {4}, pages = {283-286}, pmid = {5562849}, issn = {0001-4001}, mesh = {Adult ; Fecal Incontinence/*surgery ; Fissure in Ano/*surgery ; Humans ; Male ; Methods ; Muscles/*transplantation ; Postoperative Complications ; }, }
@article {pmid4196016, year = {1970}, author = {Montgomerie, JZ and Doak, PB and Taylor, DE and North, JD and Martin, WJ}, title = {Klebsiella in faecal flora of renal-transplant patients.}, journal = {Lancet (London, England)}, volume = {2}, number = {7677}, pages = {787-792}, doi = {10.1016/s0140-6736(70)91458-3}, pmid = {4196016}, issn = {0140-6736}, mesh = {Anti-Bacterial Agents/therapeutic use ; Cross Infection ; Feces/*microbiology ; Food Contamination ; Hospitalization ; Humans ; *Kidney Transplantation ; Klebsiella/*isolation &amp; purification ; Klebsiella Infections/drug therapy/etiology ; Personnel, Hospital ; Postoperative Complications ; Renal Dialysis ; Serotyping ; Transplantation, Homologous ; }, }
@article {pmid4196098, year = {1970}, author = {Balish, E and Pearson, TA and Chaskes, S}, title = {Irradiated humans: microbial flora, immunoglobulins, complement (C'3), transferrin, agglutinins, and bacteriocidins.}, journal = {Radiation research}, volume = {43}, number = {3}, pages = {729-756}, pmid = {4196098}, issn = {0033-7587}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antibodies/*radiation effects ; Blood Proteins/*radiation effects ; Bone Marrow Transplantation ; Candida/isolation &amp; purification ; Clostridium/isolation &amp; purification ; Complement System Proteins/*radiation effects ; Enterobacteriaceae/isolation &amp; purification ; Escherichia coli/isolation &amp; purification ; Feces/microbiology ; Humans ; Immunoglobulin G/radiation effects ; Immunoglobulin M/radiation effects ; Klebsiella/isolation &amp; purification ; Lactobacillus/isolation &amp; purification ; Male ; Nose/microbiology ; Pharynx/microbiology ; Radiation Injuries/drug therapy/*microbiology ; Skin/microbiology ; Staphylococcus/isolation &amp; purification ; Streptococcus/isolation &amp; purification ; Transferrin/*radiation effects ; gamma-Globulins/*radiation effects ; }, }
@article {pmid4195192, year = {1970}, author = {Oddie, TH and Flanigan, WJ and Fisher, DA}, title = {Iodine and thyroxine metabolism in anephric patients receiving chronic peritoneal dialysis.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {31}, number = {3}, pages = {277-282}, doi = {10.1210/jcem-31-3-277}, pmid = {4195192}, issn = {0021-972X}, mesh = {Adult ; Feces/analysis ; Female ; Humans ; Iodides/*metabolism/urine ; Iodine Radioisotopes ; Kidney Transplantation ; Kinetics ; Male ; Middle Aged ; Nephrectomy ; *Peritoneal Dialysis ; Saliva/analysis ; Sweat/analysis ; Thyroid Function Tests ; Thyroid Gland/physiology ; Thyrotropin/blood ; Thyroxine/blood/*metabolism ; Thyroxine-Binding Proteins/analysis ; }, }
@article {pmid4914945, year = {1970}, author = {Boranić, M and Van der Waaij, D}, title = {The effect of the supply of oral antibiotic on the fecal flora and mortality of mouse radiation chimeras.}, journal = {The Journal of infectious diseases}, volume = {122}, number = {1}, pages = {83-88}, doi = {10.1093/infdis/122.1-2.83}, pmid = {4914945}, issn = {0022-1899}, mesh = {Animals ; Anti-Bacterial Agents/*administration &amp; dosage ; Cyclophosphamide/administration &amp; dosage ; Digestive System/microbiology ; Disease Models, Animal ; Escherichia coli/drug effects ; Feces/*microbiology ; Female ; Immunosuppressive Agents/administration &amp; dosage ; Leukemia, Experimental/therapy ; Mice ; Proteus/drug effects ; *Radiation Chimera ; *Spleen ; Transplantation Immunology ; }, }
@article {pmid4193821, year = {1970}, author = {Suskova, VS and Khasigov, PZ and Chernov, VA and Karpov, VL and Serebriakov, NG}, title = {[Distribution and excretion of aurantin-Cl4 from intact mice and mice with transplantable tumors].}, journal = {Antibiotiki}, volume = {15}, number = {5}, pages = {437-441}, pmid = {4193821}, issn = {0003-5637}, mesh = {Animals ; Antibiotics, Antineoplastic/*metabolism ; Bile/analysis ; Carbon Isotopes ; Dogs ; Feces/analysis ; Flavonoids/administration &amp; dosage/analysis/blood/metabolism/urine ; Injections, Intravenous ; Injections, Subcutaneous ; Intestine, Small/analysis ; Kidney/analysis ; Leukemia, Experimental/*metabolism ; Liver/analysis ; Lung/analysis ; Lymphoma, Non-Hodgkin/*metabolism ; Male ; Mice ; Spleen/analysis ; Thymus Gland/analysis ; Time Factors ; }, }
@article {pmid5463105, year = {1970}, author = {Michaels, RM}, title = {Schistosoma mansoni: alteration in ovipositing capacity by transplanting between heterologous hosts.}, journal = {Experimental parasitology}, volume = {27}, number = {2}, pages = {217-228}, doi = {10.1016/0014-4894(70)90026-3}, pmid = {5463105}, issn = {0014-4894}, mesh = {Age Factors ; Animals ; Cricetinae ; Feces ; Female ; Guinea Pigs ; Intestines ; Liver ; Lung ; Mice ; Ovary ; *Ovum ; Schistosoma/analysis/anatomy &amp; histology/*growth &amp; development ; Sex Factors ; Species Specificity ; Transplantation, Heterologous ; }, }
@article {pmid5430757, year = {1970}, author = {Reichmann, W and Stücker, FJ}, title = {[Surgical treatment method for sphincter insufficiency].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {41}, number = {4}, pages = {159-162}, pmid = {5430757}, issn = {0009-4722}, mesh = {Anal Canal/anatomy &amp; histology/innervation ; Fascia/transplantation ; Fecal Incontinence/*surgery ; Humans ; Methods ; Muscles/*transplantation ; }, }
@article {pmid4392380, year = {1970}, author = {Cornelius, EA}, title = {Protein-losing enteropathy in the graft-versus-host reaction.}, journal = {Transplantation}, volume = {9}, number = {3}, pages = {247-252}, doi = {10.1097/00007890-197003000-00008}, pmid = {4392380}, issn = {0041-1337}, mesh = {Animals ; Blood Proteins/analysis ; Chromium Isotopes ; Feces/analysis ; Female ; Graft vs Host Disease/pathology ; *Graft vs Host Reaction ; Humans ; Jejunum/pathology ; Male ; Mice ; Protein-Losing Enteropathies/*complications/pathology ; }, }
@article {pmid4902489, year = {1970}, author = {Penn, I and Brettschneider, L and Simpson, K and Martin, A and Starzl, TE}, title = {Major colonic problems in human homotransplant recipients.}, journal = {Archives of surgery (Chicago, Ill. : 1960)}, volume = {100}, number = {1}, pages = {61-65}, pmid = {4902489}, issn = {0004-0010}, support = {A-6344/AA/NIAAA NIH HHS/United States ; R01 AM007772/AM/NIADDK NIH HHS/United States ; R01 AM007772/AM/NIADDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Child ; Colon/injuries ; Colon, Sigmoid/injuries ; Colonic Diseases/diagnostic imaging/*etiology ; Diverticulitis, Colonic/etiology ; Enterocolitis, Pseudomembranous/etiology ; Fecal Impaction/etiology ; Female ; Humans ; Intestinal Perforation/etiology ; *Kidney Transplantation ; Male ; Middle Aged ; *Postoperative Complications ; Radiography ; Transplantation, Homologous ; Ulcer/etiology ; }, }
@article {pmid4328377, year = {1970}, author = {Hussey, JL and Kisken, WA}, title = {Amelioration of the side effects of cyclophosphamide.}, journal = {Surgical forum}, volume = {21}, number = {}, pages = {109-111}, pmid = {4328377}, issn = {0071-8041}, mesh = {Administration, Oral ; Ampicillin/administration &amp; dosage ; Animals ; Bone Marrow Transplantation ; Cloxacillin/administration &amp; dosage ; Cyclophosphamide/administration &amp; dosage/*adverse effects ; Dehydration/chemically induced ; Diarrhea/chemically induced ; Dogs ; Feces/microbiology ; Graft Rejection ; Hematuria/chemically induced ; Injections, Intravenous ; Melena/chemically induced ; Neomycin/administration &amp; dosage ; Nystatin/administration &amp; dosage ; Pharynx/microbiology ; Polymyxins/administration &amp; dosage ; Transplantation, Homologous ; Urine/microbiology ; Vomiting/chemically induced ; }, }
@article {pmid5395241, year = {1969}, author = {Hecker, WC and Daum, R}, title = {[Incontinence following anal and rectal atresia. Surgical possibilities and results of therapy].}, journal = {Munchener medizinische Wochenschrift (1950)}, volume = {111}, number = {43}, pages = {2202-2205}, pmid = {5395241}, issn = {0027-2973}, mesh = {Adolescent ; Anal Canal ; Anus, Imperforate/*complications ; Fecal Incontinence/*etiology/surgery ; Humans ; Intestinal Atresia/*complications/surgery ; Male ; Muscles/transplantation ; Postoperative Complications ; Rectal Diseases/*complications ; }, }
@article {pmid4901129, year = {1969}, author = {Johnston, ID}, title = {Advances in surgery.}, journal = {The Practitioner}, volume = {203}, number = {216}, pages = {418-427}, pmid = {4901129}, issn = {0032-6518}, mesh = {Adrenal Gland Neoplasms/surgery ; Coronary Disease/surgery ; Cushing Syndrome/surgery ; Diverticulum, Colon/surgery ; Fecal Incontinence/surgery ; Heart Transplantation ; Humans ; Hyperaldosteronism/surgery ; Kidney Transplantation ; Liver Transplantation ; Neoplasms/surgery/therapy ; Pancreatic Neoplasms/surgery ; Postoperative Complications ; Pulmonary Embolism/prevention &amp; control ; *Surgical Procedures, Operative ; Thrombophlebitis/prevention &amp; control ; Thyroid Neoplasms/surgery ; Transplantation, Homologous ; Vagotomy ; }, }
@article {pmid4898636, year = {1969}, author = {Doherty, JE and Flanigan, WJ and Patterson, RM and Dalrymple, GV}, title = {The excretion of tritiated digoxin in normal human volunteers before and after unilateral nephrectomy.}, journal = {Circulation}, volume = {40}, number = {4}, pages = {555-561}, doi = {10.1161/01.cir.40.4.555}, pmid = {4898636}, issn = {0009-7322}, mesh = {Adult ; Creatinine/urine ; Digoxin/administration &amp; dosage/analysis/blood/*urine ; Feces/analysis ; Female ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; *Nephrectomy ; Tissue Donors ; Transplantation, Homologous ; Tritium ; }, }
@article {pmid4897283, year = {1969}, author = {Leigh, DA}, title = {The outcome of urinary tract infections in patients after human cadaveric renal transplantation.}, journal = {British journal of urology}, volume = {41}, number = {4}, pages = {406-413}, doi = {10.1111/j.1464-410x.1969.tb09940.x}, pmid = {4897283}, issn = {0007-1331}, mesh = {Adult ; Cadaver ; Escherichia coli Infections/etiology ; Feces/microbiology ; Female ; Humans ; Ischemia ; *Kidney Transplantation ; Klebsiella Infections/etiology ; Male ; *Postoperative Complications ; Proteus Infections/etiology ; Pseudomonas Infections/etiology ; Pyelonephritis/complications ; Sex Factors ; Transplantation, Homologous ; Urinary Catheterization/adverse effects ; *Urinary Tract Infections/drug therapy/etiology/microbiology ; }, }
@article {pmid5344226, year = {1969}, author = {Ráz, K and Francová, V and Franc, Z and Cerný, A and Jelínek, V and Semonský, M}, title = {Biochemistry of drugs 13. Substances with antineoplastic activity. XXX. Cancerostatic activity, absorption, tissue distribution and excretion of ethylester N--delta-(6-purinylthio)valeryl-glycine-35S-(butocine) in micel.}, journal = {Neoplasma}, volume = {16}, number = {4}, pages = {397-402}, pmid = {5344226}, issn = {0028-2685}, mesh = {Animals ; Antineoplastic Agents/analysis/*metabolism/urine ; Feces/analysis ; Intestinal Absorption ; Mice ; Neoplasm Transplantation ; Neoplasms, Experimental ; Sulfur Isotopes ; }, }
@article {pmid5750800, year = {1968}, author = {Buchwald, W and Habighorst, LV and Dudeck, J}, title = {[Animal experimental studies on tumor demonstration using radioactive silver].}, journal = {Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin}, volume = {109}, number = {5}, pages = {628-635}, pmid = {5750800}, issn = {0015-8151}, mesh = {Animals ; Feces/analysis ; Kidney/metabolism ; Liver/metabolism ; Neoplasm Transplantation ; Radioisotopes ; Rats ; Sarcoma, Experimental/*diagnosis/metabolism ; *Silver/blood ; }, }
@article {pmid4300189, year = {1968}, author = {Avioli, LV and Birge, S and Lee, SW and Slatopolsky, E}, title = {The metabolic fate of vitamin D3-3H in chronic renal failure.}, journal = {The Journal of clinical investigation}, volume = {47}, number = {10}, pages = {2239-2252}, pmid = {4300189}, issn = {0021-9738}, mesh = {Adult ; Alkaline Phosphatase/blood ; Animals ; Biological Assay ; Blood Urea Nitrogen ; Chloroform ; Cholecalciferol/analysis/blood/*metabolism/urine ; Chromatography ; Electrophoresis ; Feces/analysis ; Female ; Glomerulonephritis/metabolism ; Humans ; Kidney Failure, Chronic/blood/*metabolism ; Kidney Transplantation ; Male ; Nephrotic Syndrome/metabolism ; Proteinuria ; Pyelonephritis/metabolism ; Rats ; Renal Dialysis ; Transplantation, Homologous ; Tritium ; }, abstract = {The absorption and metabolism of vitamin D(3)-(3)H was studied in eight patients with chronic renal failure. Although the intestinal absorption of vitamin D(3)-(3)H was normal, the metabolic fate of the vitamin was abnormal as characterized by a twofold increase in fractional turnover rate, an abnormal accumulation of biologically inactive lipid-soluble metabolites, and the urinary excretion of both vitamin D(3)-(3)H and biologically inactive metabolites. Neither alterations in water-soluble vitamin D(3) metabolites nor qualitative abnormalities in protein-binding of vitamin D(3) were observed in the uremic subjects. Although hemodialysis proved ineffectual in reversing the observed abnormalities in vitamin D(3) metabolism and excretion, renal homotransplantation was completely successful in this regard. These experiments support the conclusion that the resistance to therapeutic doses of vitamin D often seen in patients with chronic renal failure and renal osteodystrophy results from an acquired defect in the metabolism and excretion of vitamin D.}, }
@article {pmid4871801, year = {1968}, author = {Idezuki, Y and Lillehei, RC and Feemster, JA and Dietzman, RH}, title = {Pancreaticoduodenal allotransplantation in dogs.}, journal = {Vascular diseases}, volume = {5}, number = {2}, pages = {78-89}, pmid = {4871801}, issn = {0506-4287}, mesh = {Animals ; Azathioprine/therapeutic use ; Biopsy ; Blood Glucose/analysis ; Dogs ; Duodenum/*transplantation ; Feces/analysis ; Glucose Tolerance Test ; Insulin/blood ; Lipids/analysis ; Methods ; Methylprednisolone/therapeutic use ; Pancreas/pathology ; *Pancreas Transplantation ; *Transplantation Immunology ; Transplantation, Homologous/mortality ; }, }
@article {pmid4869294, year = {1968}, author = {Doherty, JE and Flanigan, WJ and Perkins, WH}, title = {Tritiated digoxin excretion of patients following renal transplantation.}, journal = {Circulation}, volume = {37}, number = {5}, pages = {865-869}, doi = {10.1161/01.cir.37.5.865}, pmid = {4869294}, issn = {0009-7322}, mesh = {Adult ; Blood Urea Nitrogen ; Chromatography, Thin Layer ; Digoxin/administration &amp; dosage/analysis/blood/*urine ; Feces/analysis ; Female ; Heart Failure/metabolism ; Humans ; Injections, Intravenous ; Kidney Function Tests ; *Kidney Transplantation ; Male ; Metabolic Clearance Rate ; Middle Aged ; Transplantation, Homologous ; Tritium ; }, }
@article {pmid6027930, year = {1967}, author = {Gillette, DD}, title = {Transfer of urine into the rumen of goats by a transplanted ureter.}, journal = {The American journal of physiology}, volume = {213}, number = {1}, pages = {271-274}, doi = {10.1152/ajplegacy.1967.213.1.271}, pmid = {6027930}, issn = {0002-9513}, mesh = {Animal Feed ; Animals ; Blood Urea Nitrogen ; Dietary Proteins/*metabolism ; Feces/analysis ; Food ; Goats ; Nitrogen/analysis/*metabolism ; Rumen/*physiology ; Urea/*metabolism ; Ureter/*physiology/*transplantation ; Urine/analysis/*metabolism ; }, }
@article {pmid5964617, year = {1966}, author = {Malejka, D}, title = {Distribution of new fluorene disulphonamido derivatives in rats with transplanted Walker carcinosarcoma.}, journal = {British journal of cancer}, volume = {20}, number = {4}, pages = {857-870}, pmid = {5964617}, issn = {0007-0920}, mesh = {Animals ; Brain/metabolism ; Carcinoma 256, Walker/blood/*metabolism ; Feces/analysis ; Fluorenes/*metabolism ; Gastric Mucosa/metabolism ; Intestinal Mucosa/metabolism ; Kidney/metabolism ; Liver/metabolism ; Lung/metabolism ; Male ; Muscles/metabolism ; Neoplasm Transplantation ; Rats ; Skin/metabolism ; Spleen/metabolism ; Sulfonamides/*metabolism ; Sulfur Isotopes ; Urine/metabolism ; }, }
@article {pmid5975487, year = {1966}, author = {Pohl, V and Schnierer, M and Terstianska, G and Kirnak, J}, title = {[On the control of fecal incontinence using sphincteroplasty according to Pickrell].}, journal = {Rozhledy v chirurgii : mesicnik Ceskoslovenske chirurgicke spolecnosti}, volume = {45}, number = {9}, pages = {610-613}, pmid = {5975487}, issn = {0035-9351}, mesh = {Anal Canal/*surgery ; Diarrhea/*surgery ; Muscles/transplantation ; Transplantation, Autologous ; }, }
@article {pmid5835193, year = {1965}, author = {Glotzer, DJ and Pihl, BG}, title = {Fecal continence after rectal reconstruction.}, journal = {Surgical forum}, volume = {16}, number = {}, pages = {363-365}, pmid = {5835193}, issn = {0071-8041}, mesh = {Animals ; Colon/*surgery ; *Defecation ; Dogs ; Ileum/*surgery ; Intestinal Mucosa/transplantation ; Mucous Membrane/*transplantation ; Rectum/*surgery ; Transplantation, Autologous ; }, }
@article {pmid14231564, year = {1964}, author = {PECK, DA and HALLENBECK, GA}, title = {FECAL CONTINENCE IN THE DOG AFTER REPLACEMENT OF RECTAL MUCOSA WITH ILEAL MUCOSA.}, journal = {Surgery, gynecology &amp; obstetrics}, volume = {119}, number = {}, pages = {1312-1320}, pmid = {14231564}, issn = {0039-6087}, mesh = {*Colectomy ; *Colostomy ; *Defecation ; Dogs ; *Ileostomy ; *Ileum ; *Intestinal Mucosa ; *Mucous Membrane ; *Rectum ; *Research ; *Suture Techniques ; *Transplantation, Autologous ; }, }
@article {pmid14104161, year = {1964}, author = {DAVIS, JO and HOLMAN, JE and CARPENTER, CC and URQUHART, J and HIGGINS, JT}, title = {AN EXTRA-ADRENAL FACTOR ESSENTIAL FOR CHRONIC RENAL SODIUM RETENTION IN PRESENCE OF INCREASED SODIUM-RETAINING HORMONE.}, journal = {Circulation research}, volume = {14}, number = {}, pages = {17-31}, doi = {10.1161/01.res.14.1.17}, pmid = {14104161}, issn = {0009-7330}, mesh = {*Adrenalectomy ; *Aldosterone ; Animals ; *Arteriovenous Fistula ; *Blood ; *Blood Pressure Determination ; *Desoxycorticosterone ; Dogs ; *Feces ; *Hypophysectomy ; *Kidney ; *Kidney Function Tests ; *Kidney Transplantation ; *Metabolism ; *Research ; *Sodium ; *Urine ; *Vena Cava, Inferior ; *Venae Cavae ; *Water-Electrolyte Balance ; }, }
@article {pmid13895189, year = {1962}, author = {FRIEDBERG, W and JENKINS, VK and OV, }, title = {Albumin loss and faecal excretion of polyvinylpyrrolidone in x-irradiated mice with implanted rat bone-marrow.}, journal = {International journal of radiation biology and related studies in physics, chemistry, and medicine}, volume = {4}, number = {}, pages = {465-475}, doi = {10.1080/09553006214550251}, pmid = {13895189}, issn = {0020-7616}, mesh = {*Albumins ; Animals ; Biological Transport ; *Bone Marrow ; *Bone Marrow Transplantation ; Mice ; Povidone/*metabolism ; *Radiation Protection ; Rats ; Serum Albumin/*metabolism ; }, }
@article {pmid14432764, year = {1959}, author = {PICKRELL, K and GEORGIADE, N and RICHARD, EF and MORRIS, F}, title = {Gracilis muscle transplant for the correction of neurogenic rectal incontinence.}, journal = {The Surgical clinics of North America}, volume = {39}, number = {}, pages = {1405-1415}, doi = {10.1016/s0039-6109(16)35899-6}, pmid = {14432764}, issn = {0039-6109}, mesh = {*Abdominal Wall ; Anal Canal/*surgery ; *Defecation ; *Digestive System Surgical Procedures ; *Fecal Incontinence ; Humans ; *Muscle, Skeletal ; Thigh/*surgery ; }, }
@article {pmid13571540, year = {1958}, author = {STAHLGREN, LH and FERGUSON, LK}, title = {The surgical management of massive melena.}, journal = {American journal of surgery}, volume = {96}, number = {4}, pages = {515-521}, doi = {10.1016/0002-9610(58)90968-1}, pmid = {13571540}, issn = {0002-9610}, mesh = {Humans ; Melena/*surgery ; Skin Transplantation/*instrumentation ; }, }
@article {pmid13579962, year = {1958}, author = {BARTOLOMUCCI, E}, title = {[Transplant of the gracilis cruralis in therapy of neurogenic anorectal incontinence in children].}, journal = {La Riforma medica}, volume = {72}, number = {31}, pages = {866-870}, pmid = {13579962}, issn = {0035-5259}, mesh = {Child ; *Defecation ; *Fecal Incontinence ; Humans ; *Muscle, Skeletal ; *Muscles ; *Tendons ; *Thigh ; }, }
@article {pmid13234122, year = {1955}, author = {JENSEN, OJ and EGGERS, HE and BILL, AH and DILLARD, DR}, title = {Urinary and fecal incontinence due to congenital abnormalities in children; management by transplantation of ureters to an isolated ileostomy.}, journal = {The Journal of urology}, volume = {73}, number = {2}, pages = {322-328}, doi = {10.1016/S0022-5347(17)67403-2}, pmid = {13234122}, issn = {0022-5347}, mesh = {Child ; *Congenital Abnormalities ; *Defecation ; *Disease Management ; *Fecal Incontinence ; Humans ; *Ileostomy ; Spine/*abnormalities ; Ureter/*surgery ; *Urination Disorders ; }, }
@article {pmid13216961, year = {1954}, author = {JENSEN, OJ and EGGERS, HE and BILL, AH and DILLARD, DR}, title = {Urinary and fecal incontinence due to congenital abnormalities in children: management by transplantation of ureters to an isolated ileostomy.}, journal = {Transactions. American Urological Association. Western Section}, volume = {21}, number = {}, pages = {27-33; discussion, 34-6}, pmid = {13216961}, mesh = {Child ; *Congenital Abnormalities ; *Defecation ; *Disease Management ; *Fecal Incontinence ; Humans ; *Ileostomy ; Ureter/*surgery ; *Urination Disorders ; }, }